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'Elevated' intracellular cyclic 'AMP' 'levels,' which suppress the proliferation of naive 'T' cells and type 1 'T' helper ( 'Th1)' cells are a property of 'T' helper 2 ( 'Th2)' cells and regulatory 'T' cells. 'While' cyclic 'AMP' signals interfere with the 'IL-2' promoter 'induction,' they support the induction of 'Th2-type' 'genes,' in particular of 'il-5' gene. 'We' show here that cyclic 'AMP' signals support the generation of three inducible 'DNase' 'I' hypersensitive chromatin sites over the 'il-5' 'locus,' including its promoter region. 'In' 'addition,' cyclic 'AMP' signals enhance histone 'H3' acetylation at the 'IL-5' promoter and the concerted binding of 'GATA-3' and 'NFATc' to the promoter. 'This' is facilitated by direct 'protein-protein' interactions involving the 'C-terminal' 'Zn(2+)-finger' of 'GATA-3' and the 'C-terminal' region of the 'NFATc1' 'DNA' binding domain. 'Insm1' ( 'IA-1)' encodes a 'Zn-finger' factor that is expressed in the developing nervous system. 'Noradrenaline' is the major catecholamine produced by developing 'sympatho-adrenal' cells and is required for fetal survival. 'Reversing' the dysfunctional 'T cell' state that arises 'in cancer' and chronic viral infections is the focus of therapeutic 'interventions;' 'however,' current therapies are effective in only some patients and some tumor types. 'To' gain a deeper molecular understanding of the dysfunctional 'T cell' 'state,' we analyzed population and 'single-cell' 'RNA' profiles of 'CD8(+)' 'tumor-infiltrating' lymphocytes ( 'TILs)' and used genetic perturbations to identify a distinct gene module for 'T cell' dysfunction that can be uncoupled from 'T cell' activation. 'This' distinct dysfunction module is downstream of intracellular metallothioneins that regulate zinc metabolism and can be identified at 'single-cell' resolution. 'Our' results open novel avenues for targeting dysfunctional 'T cell' states while leaving activation programs intact. 'Newly' generated 'Gata3' hypomorphic mutant mice exhibited neonatal lethality associated with severe renal hypoplasia. 'However,' most of the 'G3YR' mice showed degenerative changes in glomerular mesangial 'cells,' which deteriorated progressively during postnatal development. 'Recent' studies have revealed various distinct 'memory-type' 'Th2' cell 'subsets,' one of which produces a substantial amount of 'IFNγ' in addition to 'Th2' 'cytokines,' however it remains unclear precisely how these 'Th2' cells produce 'IFNγ'. 'Placental' transcription factor 'GCM1' regulates trophoblast cell invasion via transcriptional activation of 'HtrA4' 'gene,' which encodes a serine protease enzyme. 'Here' we show that 'GATA3' interacts with 'GCM1' and inhibits its activity to suppress trophoblastic invasion. 'Interestingly,' 'GATA3' interacts with 'GCM1,' but not the 'GCM2' 'homologue,' through the 'DNA-binding' domain and first transcriptional activation domain in 'GCM1' and the transcriptional activation domains and zinc finger 1 domain in 'GATA3'. 'This' study uncovered a new 'GATA3' function in placenta as a negative regulator of 'GCM1' activity and trophoblastic invasion. 'GATA-3,' a member of the 'GATA' family of 'zinc-finger' 'DNA' binding 'proteins,' and 'FOXA1,' a member of the forkhead transcription factor 'family,' are both associated with estrogen receptor expression. 'Primary' and metastatic melanomas and mesotheliomas were also evaluated. 'GATA-3' and 'FOXA1' staining of estrogen 'receptor-positive' breast carcinomas was seen in 96.6 '%' and 96.2 '%', respectively. 'Direct' sequencing of 'GATA3' gene revealed a novel heterozygous missense mutation at codon 299 ( p. 'The' structure prediction showed that it caused a conformation change in this junction 'area,' affecting the spatial position of the zinc fingers. 'Functional' analysis of this mutant protein using an in vitro luciferase reporter assay system confirmed that the mutation abolished the enhancing effects of 'wild-type' 'GATA3' on the promoter activity of the consensus 'GATA' responsive element and that of human 'PTH' gene. 'We' identified a novel 'R299Q' mutation in 'GATA3' in a 'Japanese' family with 'HDR' syndrome. 'GATA1' is required for the erythroid and megakaryocytic commitment during hematopoiesis. 'An' important part of gene activation is chromatin 'looping,' the bringing together of 'DNA' elements that lie up to many thousands of basepairs apart in the genome. 'It' was recently 'suggested,' based on studies of the closely related protein 'GATA3,' that 'GATA-mediated' looping may involve interactions of each of two zinc fingers ( 'ZF)' with distantly spaced 'DNA' elements. 'Here' we present a structure of the 'GATA1' 'ZF' region bound to pseudopalindromic double 'GATA' site 'DNA,' which is structurally equivalent to a 'recently-solved' 'GATA3-DNA' complex. 'However,' extensive analysis of 'GATA1-DNA' binding indicates that although the 'N-terminal' 'ZF' ( 'NF)' can modulate 'GATA1-DNA' 'binding,' under physiological conditions the 'NF' binds 'DNA' so poorly that it cannot play a direct role in 'DNA-looping'. 'Rather,' the ability of the 'NF' to stabilize transcriptional complexes through 'protein-protein' 'interactions,' and thereby recruit looping factors such as 'Ldb1,' provides a more compelling model for 'GATA-mediated' looping. 'Conventional' 'T' cells that ectopically express 'PLZF' spontaneously acquire an 'activated,' effector phenotype. 'Several' transcription factors have been found to have critical functions in the development of both 'ILC2s' and 'T' cells. 'GATA3' immunohistochemistry was performed on 33 'placentas,' one atypical placental site 'nodule,' 25 hydatidiform moles ( 'HMs),' and 13 gestational trophoblastic tumours ( 'GTTs)'. 'All' trophoblast lineages were positive for 'GATA3'. 'Some' studies suggest that 'PQ' has effects on the immune system. 'Moreover,' previous studies have shown that 'PQ' imparted some immunosuppressive effects. 'Functionally,' iNKT cells devoid of mTORC2 signaling showed reduced number of 'IL-4-expressing' 'cells,' which correlated with a decrease in the transcription factor 'GATA-3-expressing' cells. 'Furthermore,' cellular localization of 'PLZF' was not altered in the absence of mTOR2 signaling. 'Thus,' our study reveals the 'PLZF-independent' mechanisms of the development and function of iNKT cells regulated by mTORC2. 'The' impaired 'IL-4' production by 'SAP-deficient' 24 αβ 'T' cells was associated with reduced 'IFN' regulatory factor 4 and 'GATA-3' induction following 'TCR' stimulation. 'Collectively,' these data suggest that 'SAP' is critical for regulating type 'II' 'NKT' cell responses. 'Recent' evidence suggests the involvement of sex hormone receptors in bladder cancer 'initiation,' while precise functions of androgens and estrogens in the carcinogenesis step remain poorly understood. 'Conversely,' 17 'β-estradiol' treatment increased it in 'SVHUC-control' endogenously expressing 'ERβ'. 'In' vitro transformation assay with 3-methylcholanthrene then showed a significantly higher number of colonies in 'SVHUC-AR/GATA3-shRNA,' compared with control 'SVHUC,' and 'R1881' further induced colony formation. 'Furthermore,' sex hormone signals contrary regulated 'GATA3' in the bladder. 'These' findings may offer not only a molecular basis for the 'gender-specific' difference in bladder cancer incidence but also great potential for androgen deprivation as a chemopreventive option for tumor recurrence. 'Because' 'ZNF217' associates with chromatin modifying 'enzymes,' we postulate that 'ZNF217' functions to regulate specific gene signaling networks. 'ChIP-seq' analysis reveals that the majority of 'ZNF217' binding sites are located at distal regulatory regions associated with the chromatin marks 'H3K27ac' and 'H3K4me1'. 'ERalpha' expression highly correlates with 'ZNF217' in lysates from breast tumors ( n = 15), and 'ERalpha' 'co-precipitates' 'ZNF217' and its binding partner 'CtBP2' from nuclear extracts. 'Transcriptome' profiling following 'ZNF217' depletion identifies differentially expressed genes 'co-bound' by 'ZNF217' and 'ERalpha;' gene ontology suggests a role for 'ZNF217-ERalpha' in expression programs associated with 'ER+' breast cancer studies found in the 'Molecular' 'Signature' 'Database'. 'The' maintenance of pluripotency of 'CSCs' under various pathophysiological conditions requires a complex interaction between various cellular pathways including those involved in homeostasis and energy metabolism. 'However,' the exact mechanisms that maintain the 'CSC' pluripotency remain poorly understood. 'Interestingly,' these 'pluripotency-regulating' effects of 'NAMPT' and 'POU5F1' were accompanied by contrasting levels of 'autophagy,' wherein 'NAMPT' 'KD' promoted while 'POU5F1' 'KD' inhibited the autophagy machinery. 'Most' 'importantly,' any deviation from the basal level of 'autophagy,' either increase ( via 'rapamycin,' serum starvation or 'Tat-beclin' 1['Tat-BECN1]' 'peptide)' or decrease ( via 'ATG7' or 'ATG12' 'KD),' strongly decreased the pluripotency and promoted the differentiation 'and/or' senescence of 'CSCs'. 'The' most discriminant differences between lincRNAs and mRNAs involve splicing. 'Finally,' we find that certain transcriptional properties are correlated with higher evolutionary conservation in both 'DNA' and 'RNA' motifs and are enriched in lincRNAs that have been functionally characterized. 'We' applied gene expression profile analysis and found that '\'' 'Yunma' 5 '\'' and '\'' 'Bamahuoma\'' have 'variety-specific' pathways for resisting salt stress. 'RESULTS' 'Two' thousands and sixteen kidney transplantations have been carried out from 1968-2015. 'The' majority of tumors were low stage and low grade according to the new 'ISUP' grading system. 'In' addition to providing energy and constituting cell 'membrane,' fatty acids also play an important role in adipocyte differentiation and lipid metabolism. 'As' an important member of monounsaturated fatty 'acids,' 'oleate,' together with other 'components,' is widely used to induce chicken preadipocyte differentiation. 'Gene' expression analysis of peripheral blood mononuclear cells ( 'PBMCs)' was performed using reverse 'transcription-quantitative' polymerase chain reaction ( 'RT-qPCR)'. 'Plasma' levels of 'IFN-γ' and 'IL-4' were also determined by 'ELISA'. 'T-bet' and 'IFN-γ' gene expression was significantly lower in patients group compared with healthy controls ( 'p<0'. 'A' total of 212 alleles were detected for the 18 autosomal 'STR' loci among 528 'Guangdong' 'Han' 'individuals,' and 431 haplotypes were found for 14 'Y-STRs' among 452 unrelated males. 'They' usually present 'as,' 'asymptomatic,' subcutaneous 'masses;' although symptomatic cases have been reported. 'Pediatric' dentists should be aware of the condition and consider it in the differential diagnosis of pediatric conditions involving the temporomandibular joint. 'There' were 67 patients with primary extranodal lymphoma for whom 'FDG-PET/CT' was requested for primary staging. 'SUVmean,' 'MTV' and 'TLG' were found statistically significant after multivariate analysis. 'We' show that the zinc finger motif in 'Ams2' is necessary to bind the histone gene promoter region and to activate histone gene transcription. 'An' 'N-terminal' region of 'Ams2' acts as a 'self-interaction' domain. 'Intriguingly,' 'N-terminally' truncated 'Ams2' binds to the histone gene 'promoters,' but does not fully activate histone gene transcription. 'Protein-protein' interaction ( 'PPI)' networks were constructed for the 'DEGs' with information from the 'Search' 'Tool' for the 'Retrieval' of 'Interacting' 'Genes'. ',' 'MAD1' mitotic arrest deficient like 1, cyclin ( 'CCN)B1,' 'CCNB2' and 'CCNE1]' were associated with the cell cycle and the regulation of cell 'proliferation,' while 'GNCA-unique' 'DEGs' ( e. ',' 'GATA' binding protein 6 and hyaluronoglucosaminidase 1) were implicated in cell death. 'These' common 'DEGs' could advance our understanding of the etiology of gastric 'cancer,' while the unique 'DEGs' in 'GCA' and 'GNCA' could better define the properties of specific cancers and provide potential biomarkers for 'diagnosis,' prognosis or therapy. 'GATA4' and 'GATA6' mRNAs are robustly expressed in 'fresh-frozen' human left ventricle samples as measured by highly sensitive droplet digital 'PCR' ( 'ddPCR)'. 'Importantly,' 'GATA4' mRNA levels are strongly and positively correlated with 'SCN5A' transcript levels in the human heart. 5-'ALA' associated with photodynamic therapy promotes a reduction in parasite load and an increased expression of 'IFN-γ' and 'T-bet' mRNA. 'The' 'LH' receptor ( 'LHR)' was also aberrantly expressed in a subset of ectopic endometriosis ( 21 '%') and induced strongly 'androgen-synthesizing' enzymes and 'INSL3' in 'EEC,' as in 'ovaries,' as well as endometriotic cell growth. 'We' observed that 'VASH2' induced 'EMT' 'in vitro' and 'in vivo'. 'The' transforming growth factor β1 ( 'TGFβ1)' pathway was activated by 'VASH2,' and expression of a dominant negative 'TGFβ' type 'II' receptor could block 'VASH2-mediated' 'EMT'. 'Previously,' this pathological trait has been associated with 'T' helper type 2 ( 'Th2)' cells. 'The' mRNA expression of 'IFN-γ,' 'IL-2,' 'IL-4,' 'IL-13,' and 'T-box' expressed in 'T' cells ( 'T-bet)' and 'GATA-binding' protein 3 ( 'GATA-3)' in 'PBMCs' was evaluated by reverse transcription polymerase chain reaction. 'Further' investigations reveal that signal transducer and activator of transcription 1 signaling pathway downstream of 'GATA1' has a crucial role in 'estrogen-induced' 'MK' 'polyploidization,' and 'ERβ-mediated' 'GATA1' upregulation subsequently enhances nuclear factor 'erythroid-derived' 2 'expression,' thereby promoting proplatelet formation and platelet release. 'Sex' chromosome evolution involves the accumulation of repeat sequences such as multigenic 'families,' noncoding repetitive 'DNA' ( 'satellite,' 'minisatellite,' and 'microsatellite),' and mobile elements such as transposons and retrotransposons. 'Altered' progesterone responsiveness leads to female infertility and 'cancer,' but underlying mechanisms remain unclear. 'Given' their central role in 'infection,' 'autoimmunity,' and 'malignancy,' dendritic cell deficiency or dysfunction would be expected to have clinical consequences. 'Western' blotting and immunocytochemistry demonstrated increased protein expression levels of 'α‑actin' and cardiac troponin 'T' 'expression,' and 'RT‑qPCR' revealed increased mRNA expression of 'Notch1' early in the process of differentiation ( days 1, 4 and 7), and increased mRNA expression levels of the transcription factors 'GATA' binding 'protein‑4' and 'NK2' homeobox 5 at day 28 & 'nbsp;day'. 'These' results indicate that 'L'. plantarum 'L67,' made available as yogurt starters and dietary 'supplements,' has the potential to prevent 'allergy-related' immune disorders. 'Moreover,' we propose a immunohistochemical panel of selected antibodies including those for cytokeratin 20, cytokeratin 7, estrogen 'receptor,' progesterone 'receptor,' 'E-cadherin,' gross cystic disease fluid protein 15, and 'GATA' binding protein 3 for an accurate differential diagnosis. 'Accumulating' evidence reveals that hormone 'leptin,' mainly produced by 'adipocyte,' plays a unique role in promotion of liver fibrosis. 'Results' demonstrate that leptin significantly induces 'GATA3' expression in 'HSCs' by multiple signalling pathways including 'NADPH' oxidase pathway. 'Recurrent' 'BRAF' 'V600E' mutation has been reported in 'LCH'. 'Heterodisulfide' reductase ( 'HDR)' of methanogenic archaea with its 'active-site'[4 'Fe-4S]' cluster catalyzes the reversible reduction of the heterodisulfide ( 'CoM-S-S-CoB)' of the methanogenic coenzyme 'M' ( 'CoM-SH)' and coenzyme 'B' ( 'CoB-SH)'. 'C339W)]' or the conserved linker region[c. 'Here,' we summarize the role of three classes of 'nucleases;' zinc finger nucleases ( 'ZFNs),' transcription activator like effector nucleases ( 'TALENs),' and clustered regularly interspaced palindromic repeats ( 'CRISPR)/CRISPR' associated protein 9 ( 'Cas9)' system in achieving targeted genome modifications. 'All' of these nucleases function by introducing a double stranded 'DNA' break at a specified 'site,' thereby promoting precise gene editing at a genomic locus. 'We' then apply 'RS-1' for animal production and have achieved multifold improvement on the 'knock-in' rates as well. 'Over' recent 'years,' genome editing approaches have become increasingly used as an efficient and sophisticated approach to precisely engineer the zebrafish 'genome,' which has further enhanced the utility of this organism. 'Targeted' 'genome-editing' technology using designed nucleases has been evolving 'rapidly,' and its applications are widely expanding in 'research,' medicine and biotechnology. 'Genes' associated with hereditary breast and ovarian cancer ( 'HBOC)' are often sequenced in search of mutations that are predictive of susceptibility to these cancer 'types,' but the sequence results are frequently ambiguous because of the detection of missense substitutions for which the clinical impact is unknown. 'Bone' marrow transplantation ( 'BMT)' from a 32 / 32 donor has been shown to cure an 'HIV-infected' patient. 'Taking' advantage of the 'self-renewal' and plasticity properties of stem 'cells,' in this 'study,' we successfully generated isogenic and 'six-cell' clones of bone 'marrow-derived' mesenchymal stem cells that carry the stop codon of the 'CCR5' gene by using a 'ZFN-mediated' 'homology-directed' repair technique. 'The' ability to create 'DNA' 'double-strand' breaks ( 'DSBs)' at specified genomic 'locations,' which then stimulate the 'cell\'s' naturally occurring 'DNA' repair 'processes,' has introduced intriguing possibilities for genetic modification. 'We' observed an exquisitely 'sensitive,' 'homology-dependent' preference for targeting one 'CFTR' allele versus the other. 'Although' 'TALEN' and 'CRISPR/CAS9' could induce high levels of 'HDR' in human 'cells,' their genotoxicity was significantly higher. 'The' ability to edit the genome of cell lines has provided valuable insights into biological processes and the contribution of specific mutations to disease biology. 'Paired' 'Cas9n' has been shown to be as efficient as 'Cas9' for generating insertion and deletion ( 'indel)' mutations by 'non-homologous' end joining and targeted deletion in the genome. 'However,' an efficient and reliable approach to the insertion of loxP sites flanking critical 'exon(s)' to create a conditional allele of a target gene remains an elusive goal. 'This' study indicates that conditional targeting can be accomplished effectively using paired 'Cas9n' and a single 'DNA' template. 'Their' mutational repertoire was compared to that of 'ER+/HER2-' ( n = 240), 'PAM50-defined' luminal breast cancers ( n = 209 luminal 'A;' n = 111 luminal 'B)' and invasive lobular carcinomas ( n = 127) from 'The' 'Cancer' 'Genome' 'Atlas'. 'Expression' patterns of the stem cell 'markers,' 'ALDH1A3' and 'Sox-2,' the luminal differentiation 'marker,' 'GATA3' and the proliferation index 'marker,' 'Ki-67' were analyzed using immunostaining and 'fluorescence-activated' cell sorting ( 'FACS)'. 'Epigenetic' regulation of 'Gata3' expression by chromatin remodeling complexes such as 'Polycomb' and 'Trithorax' is crucial for maintaining 'Th2' cell identity. 'Phe341Val,' first report in the 'germline)'. 'A' considerable minority 'though,' retains clonal origin and may be regarded as a distinct group for therapeutic interventions among concurrent 'BBC'. 'Comprehensive' molecular profiling has the potential to contribute to diagnostic categorization 'and,' most 'importantly,' guide 'CUP' therapy through identification of actionable lesions. 'The' 'cis-acting' element 'Rad50' hypersensitive site 6 ( 'RHS6)' in the 'Th2' locus control region is essential for regulation of the 'Th2' cytokine 'genes;' 'however,' its role in allergic airway inflammation and underlying molecular mechanisms of the regulation by 'RHS6' are poorly understood. 'RHS6' is a critical regulatory element for allergic airway inflammation and for coordinate regulation of 'Th2' cytokine genes by recruiting 'GATA3,' 'SATB1,' and 'IRF4'. 'Picroside' 'II' also inhibited the expression of 'Th2' type cytokine genes and the transcription factor 'GATA3' in the lung tissues of 'HDM-induced' mice. 'To' identify factors predicting mucosal healing in ulcerative colitis patients treated with 'anti-TNFα' agents with or without azathioprine. 'Patients' who denied combination therapy or were outside this age range received 'anti-TNFα' monotherapy ( 'controls)'. 'Mucosal' healing was defined as endoscopic subscore of 0. 'In' 'addition,' these cells exhibit increased 'β-casein' production. 'ERN1' and 'ALPK1' are potential targets for therapeutic development. 'Small' sample size and the loss of some patients to 'follow-up'. 'Leukocytes' from infants who developed 'BPD' had increased stimulated and unstimulated 'IL-4' at the 1 ( 'st)' week of 'life,' but these increases were not sustained over time. 'T-bet' was expressed significantly in 60 & 'nbsp;%' of acute 'ITP' children ( 12 / 20) ( 'P' value 0.001) and not expressed in persistent 'ITP' children ( 0 / 20), while 'GATA3' was expressed in 25 & 'nbsp;%' of persistent 'ITP' patients ( 5 / 20) ( 'P' value 0.017) and not expressed in acute 'ITP' patients ( 0 / 20). 'Fifty-three' differentially expressed 'TFs' were 'identified,' and the regulatory networks consisted of 817 'TF-target' interactions between 46 'TFs' and 602 'DEGs' in the context of breast cancer. 'Additionally,' 'TLR8' expression level increased significantly in 'MM' patients compared to healthy 'donors,' while the expression levels of 'Foxp3,' 'CD25,' 'CTLA4,' 'GITR,' 'GATA3' and 'Tbet' in 'MM' patients and healthy donors showed no significant difference. 'Although' fusion genes generated by chromosomal rearrangements are the most frequent genetic alterations in pediatric 'ALL,' fusions are insufficient for the development of this 'disease,' and 'thus,' cannot serve as therapeutic targets for 'ALL'. 'Additionally,' 10 healthy participants were selected as controls. 'Moreover,' the activities of 'T' cells and related cytokines were significantly increased of healthy controls after 'Ang' 'II' treatment ( 'p<0'. 'They' showed the upregulation of 'PPARγ' target genes and the enrichment for 'FGFR3,' 'ELF3,' 'CDKN1A,' and 'TSC1' mutations. 'They' showed the upregulation of p63 target 'genes,' the enrichment for 'TP53' and 'RB1' 'mutations,' and overexpression of 'CD49,' 'Cyclin' 'B1,' and 'EGFR'. 'Local' immune cell subsets were measured on 'formalin-fixed,' 'paraffin-embedded' tissue sections of bladder cancer by 'immunohistochemistry,' using monoclonal antibodies to 'tumor-associated' macrophages ( 'TAMs;' 'CD68,' 'CD163),' 'B-lymphocytes' ( 'CD20)' and 'T-lymphocyte' subsets ( 'CD3,' 'CD4,' 'CD8,' 'GATA3,' 'T-bet,' 'FOXP3' and 'CD25)'. 'TNF' positively modulated the expression of both transcripts in a 'Notch-dependent' 'manner;' 'however,' 'GATA3' induction was mediated by a direct 'mechanism,' while 'HOXB4' induction was indirect. 'In' spite of hyporesponsivity to 'Mycobacterium' 'leprae,' borderline lepromatous ( 'BL)' patients show clinical and immunological 'instability,' and undergo frequent acute inflammatory episodes such as type 1 reaction ( 'T1R),' which may cause nerve damages. leprae components inside the vascular compartment to skin and participation in 'T1R' physiopathology. 'U0126,' an 'ERK' 'inhibitor,' and 'SB203580,' a p38 'inhibitor,' decreased the expression of 'CD69' upon 'TCR' stimulation and inhibited 'CD4(+)' 'T' cell 'differentiation,' indicating that both 'ERK' and p38 are suggested to be critical molecular targets of costunolide. 'Compared' with healthy 'controls,' the expression level of 'IL-17A' was significantly increased in serum of patients with 'NSV,' while the productions of 'IFN-γ,' 'IL-4,' 'TGF-β' had no significant change. 28) , increased incidence of relapse ( p =. 'We' have shown that 'RV' infection of six 'day-old' mice induces mucous metaplasia and airways hyperresponsiveness which is dependent on 'IL-13,' 'IL-25' and type 2 innate lymphoid cells ( 'ILC2s)'. 'Gene' expression profiles ( 'Affymetrix' 'Human' genome 'U133' 'Plus' 2.0) of an independent cohort of adult 'T-ALL' ( n = 83) were used to identify 'ETP-ALL' and investigate 'GATA3(low)' and 'GATA3(high)' expressing 'T-ALL' patients. 'Hypomethylating' agents induced reversal of 'GATA3' 'silencing,' and gene expression profiling revealed downregulation of hematopoietic stem cell genes and upregulation of 'T' cell differentiation. 'Nonurothelial' carcinoma has not been reported to be immunoreactive for uroplakin 'II'. 'HER2' amplification might confer an aggressive and invasive pattern in primary vulvar 'Paget' 'disease,' as both amplified cases showed an invasive pattern. 'High' and medium dose of estrogen increased 'TH2' and 'Treg' cell production of interleukin ( 'IL)-4,' 'IL-10,' and transforming growth factor ( 'TGF)-β,' but concurrently resulted in a significant reduction in production of interferon ( 'IFN)-γ,' 'IL-17,' and 'IL-6'. 'For' 'instance,' 'TP53' has been simultaneously associated with tumour suppressing and promoting activities. 'In' this study we investigated the paracrine interactions between human 'DP' derived 'MSCs' ( 'hDP-MSCs)' and the 'CD4(+)' 'T' helper cell subsets to establish their immunomodulatory mechanisms. 'Cytokines' and transcription factor gene methylation were assessed. 'Proper' cell models for breast cancer primary tumors have long been the focal point in the 'cancer\'s' research. 'Besides,' 'CH2b' could markedly enhance the cytotoxic ability of the activated iNKTs. 'Therefore,' we concluded that 'CH2b,' a promising candidate 'immunostimulator,' might be used for the treatment of 'infections,' 'tumors,' autoimmune and allergic 'diseases,' and for the correction of 'Th1/Th2' balance disorders in future. 'Several' natural compounds exhibit strong capacity for decreasing triglyceride 'accumulation,' enhancing lipolysis and inducing apoptosis. 'The' percentage of apoptosis induced by 'TO' extract in 'P10' and 'P20' cells was significantly higher than that induced by all other compounds and in 'CTRL' cells. 'Sarcomatoid' dedifferentiation has been previously described in a few 'cases,' but other forms of dedifferentiation have not been reported. 1263 'dupG),' as well as 'MYCN' amplification. 'Relative' 'RT-qPCR' was used to compare expression levels of each transcript variant of the master regulators in the 'ileo-caecal' lymph nodes of uninfected controls and sheep with defined paucibacillary and multibacillary pathology. 'HBx' 'protein,' acting as a 'co-regulator,' forms a tripolymer with 'GATA2' and 'GATA3,' thus promotes the 'GATA-2' or 'GATA-3-mediated' of 'MICA/B' suppression. 'Differential' prognostic roles of 'Androgen' 'Receptor' ( 'AR)' have been proposed in breast cancer ( 'BC)' depending on tumour oestrogen receptor ( 'ER)' status. 'Effective' immunosuppression strategies and genetically modified animals have been used to prevent hyperacute and acute xenograft 'rejection;' 'however,' the underlying mechanisms remain unknown. 'Much' research effort has been focused on investigating new compounds derived from 'low-cost' 'sources,' such as natural 'products,' for treating leishmaniasis. 'Moreover,' this immunomodulatory effect was also correlated with an inhibitory effect on 'IL-1β' gene 'expression,' rather than with the expression of 'IL-1α,' 'IL-1rn' and 'TNF-α'. 'In' 'conclusion,' 'OCT-4' and 'CDX2' are essential for early development and gene expression involved in differentiation of 'ICM' and 'TE' lineages in bovine embryos. 'Predicting' and preventing exacerbations throughout life might help to reduce progressive lung function decrease and disease severity in adulthood. 'New' 'anti-IL-5' 'therapeutics,' mepolizumab and 'reslizumab,' were 'US' 'Food' and 'Drug' 'Administration' approved for the treatment of patients with severe eosinophilic asthma. 'Estrogen' receptor ( 'ER)/GATA3/Forkhead' box 'A1' ( 'FOXA1)' network is necessary for the 'ERα' functional signature. 'However,' the effects of 'BCG' vaccination over time on the 'T' helper subpopulation and the microRNAs involved in adulthood have not been studied. 'The' expression levels of miRNAs and transcription factors were evaluated using 'qRT-PCR'. 'Data' integration has become a useful strategy for uncovering new insights into complex biological networks. 'Overexpression' of 'miR-720' attenuated 'M2' phenotype expression and thus inhibited 'M2' polarization. 'GATA3,' 'ERG' and 'MYB' serve important roles in 'RCC' while 'FOXC1,' 'ESR1,' 'FOXL1,' 'PATZ1,' 'STAT5A' and 'PELP1' may be potential genes associated with 'RCC'. 'Positive' 'TOX' expression was identified in 73.6 '%' of 'MF' cases and in 31.6 '%' of 'BID/NS'. 'Despite' being equally 'obese,' 'IR' individuals had significantly lower plasma leptin and adiponectin levels and higher 'IL-6' levels compared with 'age-matched' 'IS' counterparts. 'Elevated' systemic 'IL-6' in 'IR' individuals was associated with hyperplasia of adipose 'tissue-derived' 'SVF' 'cells,' despite higher frequency of hypertrophied adipocytes. 'Complete' loss of at least one 'SWI/SNF' subunit limited to the undifferentiated component was detected in 10 / 14 cases ( 71 & 'nbsp;%)'. 'Hearing' impairment most often involves loss of sensory hair cells and auditory neurons. 'Ex' vivo 'PBMC' α7nAChR mRNA expression was increased in both 'AD' 'groups,' while 'GATA3' expression was not. 'More' 'importantly,' the loss of 'WDR77' expression that results from 'E2F' and 'GATA' switches is required for cellular differentiation of erythroid and lung epithelial cells. 'Th2-eosinophil' immune responses are well known for mediating host defence against helminths. 'Subsequently,' 'miR-503' further modulated the activation of 'ZNF217-downstream' 'epithelial-mesenchymal' transition ( 'EMT)' genes. 'GATA2' was required for the in vitro generation of 'DCs' from 'Lin(-)Sca-1(+)Kit(+)' 'cells,' common 'myeloid-restricted' 'progenitors,' and common dendritic cell 'precursors,' but not common 'lymphoid-restricted' progenitors or 'granulocyte-macrophage' 'progenitors,' suggesting that 'GATA2' functions in the myeloid pathway of 'DC' differentiation. 'Aberrant' mucosal immunity suggests that 'CD' is a 'T' helper type 1 cell ( 'Th1)-driven' 'disease,' whereas 'UC' as 'Th2-driven' response. 'Its' level of expression was found to be an independent factor predicting cancer recurrence. 'The' 'tumor,' 'unfortunately,' recurred 7 years later with associated multiple lung metastases. 'Following' strict cytology smear screening 'criteria,' targeted next generation sequencing ( 'NGS)' using a 160 cancer gene panel was performed. 'Multiple' regression 'analysis,' 'however,' found that joint expression of 'IL-17A,' 'IL-17F,' 'IL-21,' 'RORC,' and 'TGF-β' was significantly predictive of 'REI' ( 'P < 0'. 'Previous' studies have shown high heritability for age of smoking initiation and 'cessation;' 'however,' 'time-to-event' 'genome-wide' association studies aiming to identify underpinning genes that accelerate or delay these transitions are missing to date. 'We' investigated which single nucleotide polymorphisms ( 'SNPs)' across the whole genome contribute to the hazard ratio of transition between different stages of smoking behavior by performing 'time-to-event' analyses within a large 'Finnish' twin family cohort ( 'N = 1962),' and further conducted mediation analyses of plausible intermediate traits for significant 'SNPs'. 'Whereas' the majority of invasive mammary carcinomas with neuroendocrine differentiation were positive for estrogen receptor and 'GATA3,' metastatic neuroendocrine neoplasms were typically negative for estrogen receptor and 'GATA3,' and metastatic 'well-differentiated' neuroendocrine tumors often showed immunoreactivity for 'site-specific' markers. 'Chemoattractant' 'receptor-homologous' molecule expressed on 'Th2' cells ( 'CRTh2)' is a receptor for 'PGD2' and expressed by 'T' 'cells,' 'eosinophils,' 'basophils,' and 'ILC2' cells. 'Histologic' features included mixed 'microcystic,' 'solid,' follicular and papillary 'architecture,' prominent 'nucleoli,' abundant nuclear grooves and rare nuclear 'pseudo-inclusions'. 'Given' the immunophenotype of this 'case,' it is possible that at least some 'ETV6-NTRK3' fusion positive 'PTC' are actually 'MASC' masquerading as papillary thyroid carcinoma. polygyrus bakeri infection induces a novel subset of 'MDSC' that suppress 'CD4(+)' 'Th2' responses and promote chronic infection. 'During' mouse early 'embryogenesis,' blastomeres increase in number by the morula stage. 'Epithelial-to-mesenchymal' transition markers were frequently 'expressed,' including vimentin ( 26 of 26; 100 '%'), 'FoxC2' ( 26 of 26; 100 '%'), 'SNAIL' ( 23 of 26; 88.5 '%'), and 'ZEB1' ( 18 of 26; 69.2 '%'). 'S100A8' and 'S100A9' are 'calcium-binding' proteins that are secreted primarily by granulocytes and 'monocytes,' and are upregulated during the inflammatory response. 'The' dominant 'T cells' infiltrating a range of inflamed 'IgG4-RD' tissue sites were clonally expanded 'CD4(+)' 'CTLs' that expressed 'SLAMF7,' granzyme 'A,' 'IL-1β,' and 'TGF-β1'. 'Clinical' remission induced by 'rituximab-mediated' 'B-cell' depletion was associated with a reduction in numbers of 'disease-associated' 'CD4(+)' 'CTLs'. 'Polyclonal' and allogeneic stimulation induced higher levels of 'CD30' transcripts in 'ESRDP' than in 'HC' ( both 'P<0'. 'Reflecting' an activated immune 'state,' 'ESRDP' exhibited after allostimulation upregulation of 'CD30' transcripts in 'T' 'cells,' which was associated with 'Th1' and proinflammatory responses. 'Several' candidate genes for 'ALL,' such as 'COL6A6' and 'COL5A1,' were identified through targeted maximum likelihood estimation. 'As' 'DCA' inhibits aerobic 'glycolysis,' which is a prerequisite for 'CD4+' 'T-cell' proliferation and differentiation into effector 'T-cells,' its possible immunosuppressive role in mixed lymphocyte reaction ( 'MLR),' a model of 'alloreactivity,' was investigated. 'Successful' reprogramming requires stable binding to a nucleosomal 'site;' activation 'domain-dependent' recruitment of 'co-factors' including 'BRG1,' the 'ATPase' subunit of the 'SWI/SNF' chromatin remodeling 'complex;' and appropriate genomic context. 'These' results demonstrated that 'Cg-SCL' could be used as haematopoietic specific marker to trace potential developmental events of hematopoiesis during ontogenesis of 'oyster,' which occurred early in blastula stage and maintained until 'D-veliger' larvae. 'Hence,' metastases from breast carcinomas with unrecognized neuroendocrine features may lead to false diagnoses of primary neuroendocrine tumors at different metastatic 'sites,' such as the pancreas. 'Further' analyses of publicly available datasets showed that 'PYGM' is dramatically underexpressed in common cancers as compared to normal tissues and that low expression in tumors is correlated with poor 'relapse-free' survival. 'Exercise' induced inflammatory response in 'SLE' remains to be fully elucidated. 100 '%' of male adenocarcinomas also exhibited strongly positive expression in the nuclei of tumor cells for 'PCNA,' with 25 '%' expressing 'AR' and only 8 '%' showing positivity for 'ER'. 'Male' carcinomas did not express 'PgR' or 'GATA3' and none of the 'tumors,' male or 'female,' were positive for 'HER2'. 'In' 'contrast,' 'MNU-induced' mammary adenocarcinomas in male rats showed no reactivity for 'ER,' 'PgR,' 'HER2' or 'GATA3,' suggesting no hormonal dependency. 'Considerable' progress has been made in understanding the mechanisms that control the production of specialized neuronal types. 'Together,' our results identify a miRNA family with important immunological roles and suggest that tight regulation of 'miR-23∼27∼24' clusters in 'T' cells is required to maintain optimal effector function and to prevent aberrant immune responses. 'We' examined whether 'CGRP' regulates the outcome of 'Ag' presentation by 'Langerhans' cells ( 'LCs)' to 'T' cells through actions on microvascular endothelial cells ( 'ECs)'. 'E-,' 'N-,' 'P-,' 'VE-,' 'Proto-,' desmosomal and 'FAT' cadherins have been found to regulate breast cancer in positive as well as negative 'fashion,' whereby both 'Ecadherin' ( 'CDH1)' and 'N-cadherin' ( 'CDH2)' contribute significantly towards transitioning from epithelial state to mesenchymal state ( 'EMT)' and enacting the abnormal cells to invade and metastasize nearby and distant tissues. 'PCR' revealed that the 'THK' cells exhibited the transcripts of 'toll-like' receptor 1 ( 'TLR1),' 'TLR2,' 'TLR3,' and 'CD200,' of which concern with immunity as well as the transcripts of vascular endothelial growth factor receptor 3, 'angiomotin,' and 'angiopoietin-like' protein 2 that associate with angiogenesis regulation and macrophage proliferation. 'Flow' cytometry ( 'FCM)' studies revealed that 'ES' substantially inhibited 'Th17' 'cells\'' percentage. 'Although' many studies have implicated the crosstalk between the 'Wnt' and 'PKC' signaling pathways in tumor initiation and 'progression,' the molecular roles of 'PKC' isoforms in the 'Wnt' signaling pathway remain poorly understood. 'His' cranial computed tomography revealed multiple calcifications in bilateral centrum 'semiovale,' corona 'radiata,' and basal ganglions suggesting a persistent hypoparathyroidism. 'Despite' the defect in 'maturation,' upon murine 'CMV' 'infection,' 'NK' cells from 'NKp46-Cre-Gata3(fl/fl)' mice expanded 'vigorously,' achieving 'NK' cell frequencies surpassing those in controls and therefore provided comparable protection. 'The' first two are cytoplasmic markers that show comparable sensitivities for breast 'cancer,' although relatively few of the published studies have employed the same antibodies against the target 'molecule,' making direct comparisons challenging. 'Whole-genome' sequencing identified novel mutations in 'GATA3,' which causes 'HDR' syndrome ( hypoparathyroidism and 'deafness),' and 'STS,' which causes 'X'-linked congenital ichthyosis. 'This' case demonstrates the power of 'whole-genome' ( or 'exome)' sequencing for patients with complex clinical presentations involving endocrine abnormalities. 'Genetic' selection for enhanced immune response has been shown to decrease disease occurrence in dairy cattle. 'Further,' 'H-CMIR' cows had increased expression of the 'IFNG' gene at 16, 24, and 48 h 'post-treatment' with 'ConA,' although expression of the 'type-1' transcription factor gene 'TBX21' did not differ between immune response groups. 'Studies' by others identified an enhancer in human 'HDAC9' that correlated with 'TWIST1' expression. 'Also,' the percentage of regulatory 'T' cells ( 'Treg)' in the spleens of mice sensitized with 'OVA' plus 'CTB' was lower than that in mice orally sensitized with 'OVA' alone. 'Immunocytes' and cytokine secretions involved in the mouse cardiac allografting model with 'Tk-tPN' treatment were characterized. 'Identification' of critical genes and analysis of their functions through 'Toll-like' receptor ( 'TLR)'-initiated signalling and the possible epigenetic changes were performed. 'Thioredoxin-1' ( 'Trx-1)' plays the roles in regulating redox and inhibiting inflammation. 'Previous' studies have shown that 'BMP4' may play an important part in the development of auditory neurons ( 'ANs),' which are degenerated in sensorineural hearing loss. 'Flow' cytometric analysis showed that the isolated cells expressed typical 'MSC' surface markers. 'Interestingly,' 'AcRE' suppressed 'IL-4-induced' 'STAT6' phosphorylation in both primary cultured splenocytes and 'HaCaT' 'cells,' and 'TMA-induced' 'GATA3' mRNA expression ex vivo. 'Recently,' it has been found that the 'HMGB1' was abnormally expressed in induced sputum and plasma of asthmatic patients. 'Both' cytokines induce 'fate-decisive' transcription factors such as 'GATA3' and 'TBX21' that antagonize the polarized development of opposite phenotypes by direct regulation of each 'other\'s' expression along with many other target genes. 'Our' data indicated that in addition to 'JunB,' the 'SNP' at-1035 /-1023 influenced 'GATA-3' and 'MEF-2' binding 'affinity,' potentially altering 'IL12RB2' transcriptional activity. 'Mesonephric' neoplasms reveal relatively 'low-grade' nuclear 'feature,' characteristic immunoprofiles ( immunonegative for 'ER' and 'PR,' and immunopositive for 'CD10,' 'PAX2,' 'PAX8,' and 'GATA3),' and unique tumor location ( 'myometrium),' whereas 'Müllerian' neoplasms such as endometrial adenocarcinoma show various 'morphology,' immunopositivity for 'ER' and 'PR,' and primarily endometrial location. 'Evidence' from gene expression across the three cohorts has consistently indicated that the 'MR16' can be divided into two groups that demonstrate 'subtype-specific' gene expression patterns. 'The' prognostic significance of 'GATA3' in breast cancer remains controversial. 'CCL25' plays an important role in 'T-cell' 'development,' whereas 'IL17C' regulates innate epithelial immune responses. 'Significant' difference ( 'p<0'. 'Differential' diagnosis of 'BAC' and 'CAC' remains 'difficult,' but positive staining for keratin 7 in nuclear 'ß-catenin-negative' tumours argues for 'BAC'. 'Mechanistically,' miR573 directly targets the fibroblast growth factor receptor 1 ( 'FGFR1)' gene. 'Consequently,' 'miR-573' modulates the activation of 'FGFR1-downstream' signaling in response to fibroblast growth factor 2 ( 'FGF2)'. 'Borrelidin' suppressed the mRNA expression of two master regulators of adipocyte 'differentiation,' peroxisome 'proliferator-activated' receptor gamma ( 'PPARγ)' and 'CCAAT/enhancer' binding protein ( 'C/EBPα)'. 'This' is a convenient and practical simplification that overshadows the 'sublime,' and potentially 'critical,' phenotypic plasticity found within the adult 'HS-MEC' population. 1 is predominantly expressed in dendritic cells ( 'DCs)' and is essential for 'DC' differentiation. 'Although' there are several reports that 'PU'. 'This' report indicates that p. 'Catalpol' alleviated bone loss effectively by regulating 'Th1/Th2' polarization. 'Here,' we report that 'Bcl11b,' previously considered a 'T-cell-specific' transcription 'factor,' acted directly upstream of the key 'ILC2' transcription factor 'Gfi1' to maintain its expression in mature 'ILC2s'. 'On' the 'contrary,' a 'MEK' inhibitor suppressed 'ILC2' proliferation and cytokine production. 'Mechanistically,' 'AICAR-activated' 'AMPK' inhibits 'GSK3β' through a phosphorylation process that stabilizes 'β-catenin'. 'WNT/β-catenin' signaling has been described as a crucial regulator of embryonic stem cells and embryogenesis. and 'Taiwan,' have stated that 'IL-25' is a strong inflammatory cytokine protein which is involved in allergic inflammations. 'Urobasal' tumors maintain an apparent urothelial differentiation axis composed of 'PPARG/RXRA,' 'FOXA1/GATA3' and anterior 'HOXA' and 'HOXB' genes. 'Therapeutic' targeting of 'GATA3,' an important transcription factor of the 'Th2' 'pathway,' may be beneficial. 'SNPs' at a region on 13 q21. 'Significantly' stronger correlation was observed between 'primary/metastatic' 'GATA3' expression['Pearson\'s' 'correlation=0'. 'Helicobacter' pylori ( 'H'. 'Fine' mapping reveals that two variants correlated with 'rs73635312[A]' occur in conserved binding sites for the 'GATA3' transcription factor. 'Besides' 'IFN-γ,' 4 inhibited dose dependently expression and production of representative 'Th17' 'cytokine,' 'IL-17,' in these cells. 'Determining' histologic types of lung cancer on biopsies can be difficult. 'By' applying a 'MPS' diagnostic panel targeting 129 known deafness 'genes,' we identified a novel frameshift 'GATA3' 'mutation,' c. 'Eosinophils' are one of the key inflammatory cells in asthma. 'Asthma' is a serious global health problem characterised by airway 'inflammation,' airway epithelial wall 'shedding,' enhanced mucus 'production,' increased 'IgE' levels and airway hyperresponsiveness. 'Asthma' is a serious health problem causing significant mortality and morbidity globally. 'Serum' levels of 'CXCL16,' 'IL-6,' 'TNFα' and 'IL-10' were also significantly increased after exercise. 'However,' 'KLF2' also induced expression of the transcription factor 'Blimp-1,' which repressed transcription factor 'Bcl-6' and thereby impaired 'Tfh' cell differentiation. 'PBMC' isolated from patients with severe atopic asthma and 'COPD,' as well as healthy subjects were stimulated with rDer p 1 'DG,' rFel d 1 'DG' and 'LPS'. 'Selective' inhibitors suggested that 'RSV-induced' 'IDO' activity was dependent on the retinoic 'acid-inducible' 'gene-I' ( 'RIG-I)' related pathway via 'NF-κB' and p38 'MAPK'. 'In-vivo' 'TNFRSF4/25' antibody 'co-stimulation' enhanced 'Aβ42' specific 'T' cell responses with initial 'Th2' expansion and subsequent development of 'Aβ42' specific 'CD4+CD25+Foxp3+' cells. 'Milk' 'EPIT' enhanced methylation of the 'GATA-3' promoter region. 'Twenty-eight' cases ( 88 '%') expressed 'MAGEC2' and 'CAM5'. 'Differentially' expressed genes were assessed for their correlation with the sequential organ failure ( 'SOFA)' score. 'Prenatal' dexamethasone exposure has been reported to increase allergy potential in childhood possibly by interference with normal immunological development in utero. 'Using' experimental 'models,' 'ILC2' have been implicated in allergic 'diseases,' such as asthma and atopic 'dermatitis,' but also in metabolic homeostasis. 'Echocardiography' finding revealed secundum atrial septal deftect. 'In' the experiments in 'vitro,' it has been first found the recombinant 'galectin-3' ( 0.5 'mg/mL)' 'up-regulating' the expression of transcription factors 'Gata-3' and 'Rorc' mRNAs and 'down-regulating' the mRNA expression of transcription factors 'T-bet' and 'FoxP3'. 'It' catalyzes the phosphorylation of choline to phosphorylcholine in the presence of 'ATP' and 'Mg2+' during the biosynthesis of 'phosphatidylcholine,' the major phospholipid in eukaryotic cell membranes. 'Chromatin' immunoprecipitation assays were conducted to study progestin modulation of recruitment of transcription factors to 'GATA3' promoter. 'Tree' shrew has increasingly become an attractive experimental animal model for human 'diseases,' particularly for breast cancer due to spontaneous breast tumours and their close relationship to primates and by extension to humans. 'Of' 'these,' three induced breast tumours were intraductal papillary carcinomas and one was invasive ductal carcinoma ( 'IDC)'. 'Furthermore,' rgTPO and rgKITLA synergistically stimulated thrombocytic 'colony-formation'. 'Remarkably,' such protection occurred without causing severe combined immunodeficiency. 'CD4' and 'GATA3' mRNA expressions exhibited a similar pattern to 'IgT' in the hindgut. 'Brenner' tumors are composed of 'urothelial/transitional-type' epithelium 'and,' 'hence,' are morphologically similar to 'Walthard' nests and 'tubal/mesothelial' transitional metaplasia. 'Astragalus' 'membranaceus,' a traditional 'Chinese' 'herb,' has been used to improve airway inflammation and asthma. membranaceus has immunotherapeutic effects on 'asthma,' a chronic inflammatory mucosal disease that is associated with excess production of 'IgE,' 'eosinophilia,' 'T' helper 2 ( 'Th2)' 'cytokines,' and bronchial hyperresponsiveness. 'With' the new sequence 'technologies,' the finding of key gene mutation in 'Th1/Th2' cells has been proved to be related to human diseases. 'ASH2L' is a component of 'MLL' complexes that confer 'H3K4' trimethylation. 'Salivary' gland adenocarcinomas have not been evaluated for potential aberrant caspase 14 expression. 'Thus,' recognition of expression in trophoblastic tumors is 'important,' because it can present a diagnostic pitfall in the assessment of suspected metastatic bladder or breast carcinomas involving the gynecologic tract. 'Therefore,' efforts have been made to explore black gram allergy using in vivo and in vitro approaches. 'Enhanced' levels of specific 'IgE,' 'IgG1/IgG2a' ( p & 'lt;' 0.05), histamine ( p & 'lt;' 0.05), clinical 'symptoms,' pathological indications in the 'lungs,' intestine and spleen were evident in black gram sensitized 'BALB/c' mice. 'Extracellular' calcium participates in several key physiological 'functions,' such as control of blood 'coagulation,' bone calcification or muscle contraction. 'Lastly,' 'CBP' and p300 regulate the epigenetic status and function of 'Foxp3'. 'WYRE' significantly reduced viability of both cell lines and enhanced mRNA content of 'GATA3' in a 'concentration-dependent' 'manner;' 'however,' 'DNMT' mRNAs ( 'DNMT1,' 3 'A,' 3 'B)' were found to increase significantly only in 'MDA-MB-231' cells. 'Mutations' and genomic rearrangements involving the eight genes were screened by targeted 'next-generation' sequencing ( 'NGS)'. 'Gut' microbiota mediated 'low-grade' inflammation is involved in the onset of type 2 diabetes ( 'T2DM)'. 'In' establishing 'PPR' 'polarity,' both 'Gata3' and 'Foxi1' inhibit 'Bmp' 'signaling,' whereas 'Foxi1' 'inhibits,' but 'Gata3' 'enhances,' 'Fgf' sensitivity of the 'PPR' cells. 'Characteristic' 'gata3/tbx21' has potential as a biomarker for the status of mycobacterial disease. 'Its' gene expression is limited at the very surface of the stratum granulosum ( 'SG),' whereas expression of kallikreins ( 'KLKs)' encoding proteases is usually found throughout the stratum spinosum and 'SG'. 'Luciferase' assay targeting the 'SPINK5' promoters ( nucleotide-676 /-532 and-318 /-146 from the major transcription start 'site)' showed high intensity in 'NHEK' human keratinocyte. 'The' nested component expressed cytokeratins 7 , 20, 'CAM5'. 'Whether' 'nuclear-WASp' requires the integration of its 'actin-related' protein ( 'ARP)2/3-dependent' cytoplasmic function to reprogram gene 'transcription,' 'however,' remains unresolved. 'Upon' chromosomal microarray he was found to have an interstitial deletion at 10 'p,' which produced a partial deletion in the 'GATA3' gene. 'Two' 'Cdc4' phosphodegron ( 'CPD)' candidate 'sequences,' consensus 'Fbw7' recognition 'domains,' were identified in 'GATA3,' and phosphorylation of 'Thr-156' in 'CPD' was required for 'Fbw7-mediated' ubiquitylation and degradation. 'CD70-expressing' 'CD4' 'T' cells are enriched in 'RA' and promote autoimmunity via 'co-stimulatory' 'CD70-CD27' interaction. 'Once' induced by acute priming 'signals,' such as 'IL-4,' 'GATA3' poises the 'Th2' cytokine locus for rapid activation and establishes a 'positive-feedback' loop that maintains elevated 'GATA3' expression. tuberculosis 'infection,' revealing a potential negative regulatory role for 'Gab2' in immunity to 'TB'. 'Unlike' previously reported 'Jarid1b(-/-)' 'strains,' the majority of these 'Jarid1b(-/-)' mice were viable beyond embryonic and neonatal stages. 'The' transcription factor 'ZEB1' is a known driver of 'EMT,' and mediators of 'ZEB1' represent potential therapeutic targets for metastasis suppression. 'Twenty' 'CRS' subjects and 19 controls were recruited. 'Hispanic' children have a higher incidence of acute lymphoblastic leukemia ( 'ALL)' than 'non-Hispanic' whites but tend to be diagnosed at older ages. 'Our' results identify a novel 'gene-diet' interaction with processed meat for colorectal 'cancer,' highlighting that diet may modify the effect of genetic variants on disease 'risk,' which may have important implications for prevention. 'At' age 10 , the odds of asthma tended to decrease as cg12405139 ( 'GATA3)' methylation increased ( 'log-OR' =-12.15 ; 'P' = 0.049) ; this effect disappeared by age 18. 'Nucleocytoplasmic' shuttling of macromolecules is a 'well-controlled' process involving importins and exportins. 'Overall,' 69 '%' ( 66 / 96), 15 '%' ( 14 / 96), and 35 '%' ( 34 / 96) of 'ER-negative' breast carcinomas expressed 'GATA-3,' 'GCDFP-15,' and 'MGB,' respectively. 'About' 20 '%' of all these sufferers have experienced asthma exacerbation. 'Subsequently,' 'CD4(+)T' cells and alveolar macrophages were sorted and purified from mice lungs in different groups. 'Isl1' deficiency led to nearly complete absence of the pyloric outer longitudinal muscle layer at embryonic day 18.5, which is consistent with 'Gata3' null mouse phenotype. 'Meta-analysis' was used to compare genotype frequencies between the participating 'centres,' allowing for heterogeneity. 'We' applied in silico phylogenetic footprinting on the upstream regulatory regions of a diverse set of human 'UMOD' orthologs to identify conserved binding motifs and corresponding position specific weight matrices. 'No' case expressed uroplakin. 'Irradiation' also modified 'TLR4' and 'TLR5' expression on the surface of both 'populations,' but 'LPS' and flagellin each subsequently normalized them. 'Audiogram' confirmed sensorineural hearing loss of both sides. 'Bavachinin' and compound 'B' inhibited green fluorescent protein ( 'GFP)' production from the 'T' cells of 'IL-4-GFP-enhanced' transcript ( 4 'GET)' 'mice,' whereas compound 'A' did not. gingivalis serotypes induce higher osteoclasts 'activation,' by increased 'Th17-associated' 'RANKL' 'production,' and an 'antigen-specific' memory 'T-lymphocyte' response. 'Vitamin' 'D' suppresses inflammation and vitamin 'D' deficiency is linked to the severity of asthma symptoms. 'FOXA1' may be useful in identifying those patients who may not require adjuvant 'CT'. 'Oleanolic' acid suppressed eosinophil 'infiltration,' allergic airway 'inflammation,' and 'Penh,' which occurred by suppressing the production of 'IL-5,' 'IL-13,' 'IL-17,' and 'ovalbumin-specific' 'IgE' through the upregulation of 'T-bet' and 'Foxp3,' and the downregulation of 'GATA-3' and 'RORγt'. 'Results' showed that the 'MAE' exercise for 12 weeks 'didn\'t' change red blood cells or total leukocytes but increased lymphocyte counts. 'These' findings signify the contribution of myeloid cells in preventing 'Th2-mediated' diseases and suggest their possible application as therapeutics. 'Often' the distinction of cutaneous apocrine carcinoma from metastatic mammary apocrine carcinoma to the skin can be a diagnostic dilemma because both tumors share similar histologic features and have overlapping immunohistochemical profile. 'We' show that the transcription factor 'Mafb' drives the formation of auditory ribbon 'synapses,' which are specialized for rapid transmission from hair cells to spiral ganglion neurons ( 'SGNs)'. 'CtBP1' epidermis displayed 'hyperproliferation,' loss of 'E-cadherin,' and failed terminal differentiation. 'The' 10 transcription factors may serve as potential therapeutic targets for 'NPC_I'. 'When' ectopically expressed in 'basal-like' breast cancer 'cells,' 'GATA-3' abrogated 'TGFβ-' and 'Smad4-mediated' overexpression of fascin and other 'TGFβ' response 'genes,' invadopodium 'formation,' cell 'migration,' and 'invasion,' suggesting suppression of the canonical 'TGFβ-Smad' signaling axis. 'Therefore,' it was hypothesized that 'SHD' reduced the uterine bleeding in 'RU486' medical abortion by inducing 'Th1/Th2/Th17/Treg' paradigm bias. 'However,' it is unclear whether or not vitamin 'A' can regulate 'Th1-Th2' balance under a strong 'Th1-polarizing' condition. 'If' a patient has a preexisting 'Th1' immunologic response within the 'tumor,' there is no value in using a therapy intended to create a 'Th1' immunologic response. 'Participants' in 'PLCD' and 'PWLCD' groups received 200 'g/day' yogurt containing 'Lactobacillus' acidophilus 'La5,' 'Bifidobacterium' 'Bb12,' and lactobacillus casei 'DN001' 10 ( 8) 'cfu/gr'. 'Despite' evidence it may also be expressed in multipotent hematopoietic stem cells ( 'HSCs),' any role for 'GATA-3' in these cells has remained unclear. 'Th2-driven' disease has been well described under some conditions for 'RSV-infected' mice. 'GRNs' are especially crucial at the onset of organ development where a few regulatory signals establish the different programs required for tissue organization. 'Technological' advances have expanded our view of these 'lineage-specifying' transcription factors to the whole genome and revealed unexpected interplay between them. 'Administration' of indoxyl sulfate in rats reduced renal expression of slco4c1 and under this 'condition,' plasma level of 'guanidinosuccinate,' one of the preferable substrates of 'slco4c1,' was significantly increased without changing plasma creatinine. salivarius 'UCC118' skewed towards an immune regulatory phenotype in the small intestinal lamina propria ( 'SILP)'. lactis 'MG1363' had immunomodulatory effects. 'Ethanol-exposed' pdgfra mutants have profound craniofacial defects that include the loss of the palatal skeleton and hypoplasia of the pharyngeal skeleton. 'The' permanent 'over-expression' of 'miR-146a' was established using a lentivector that expressed 'GFP' 'hsa-mir-146a' miRNA. 'Our' study thus demonstrates an essential role for 'GATA-3' in controlling the maintenance and proliferation of 'T' cells and provides insight into immunoregulation. 'The' current study sought to delineate the gene expression profile of the host response in the caecum and colon during acute infection with 'Clostridium' difficile in a mouse model of 'infection,' and to investigate the nature of the unfolded protein response in this process. 'Transcriptionally,' 'ERα' either binds 'DNA' directly through conserved estrogen response element sequence motifs or indirectly by tethering to other interacting transcription factors and nucleate transcriptional regulatory complexes which include an array of 'co-regulator' proteins. 'We' found that a limited number of microRNAs exhibited marked 'up-' or downregulation following 'early-life' infection and 'sensitisation,' for many of which the levels of expression were further changed following chronic challenge with the sensitizing antigen. 'Although,' the 'TGFß' pathway has been shown to play a key role in tumorigenesis and 'metastasis,' only a limited number of models have been developed to understand this process. 'We' have recently described the presence of the erythropoietin receptor ( 'EPO-R)' on 'CD4(+)' lymphocytes and demonstrated that its expression increases during their 'activation,' reaching a level reported to be typical for erythroid progenitors. 'Similarly,' we ectopically overexpressed 21 different histone acetyltransferases and found that 'KAT6A,' 'KAT6B' and 'KAT7' induce 'BRM' 'expression,' whereas 'KAT2B' and 'KAT8' induce its acetylation. 'We' selectively knocked down 'GATA3,' 'MEF2D,' 'HDAC3' and 'HDAC9,' and found that each 'gene-specific' knockdown induced growth inhibition. 'Among' these 'cells,' 'IFN-γ-producing' 'T' cells ( 'TH1)' are recognized as having a 'pro-atherogenic' role. 'Hematopoiesis' is a classic system with which to study developmental potentials and to investigate gene regulatory networks that control choices among alternate lineages. 'T-cell' progenitors seeding the thymus retain several lineage potentials. 'Decreased' 'interferon-γ' and increased 'interleukin-4' levels in the blood and 'splenocytes,' and lowered 'T-bet' and elevated 'GATA-3' mRNA expressions were found in the spleen in the 'medium,' high and overdose groups when compared with the control or low dose group ( 'P<0'. 'Bcl6' represses and 'Stat3' activates 'miR-21' transcription through a 'Stat3' binding element in the 'promoter,' indicating opposing regulation of 'miR-21' by the two transcription factors via the same 'DNA' site. 'Increased' 'miR-21' promoted 'Th2' and 'Treg' gene expression in 'wild-type' 'Tregs'. 'Malaria' parasites associated with asymptomatic infections seem to result in increased 'TNFRII' expression on 'Tregs,' as well as suppressed 'Th2' cytokine 'responses,' features that might be important for survival of the parasites in asymptomatic carriers. 'PCM1-JAK2' signalling required 'pSTAT5,' supporting a general paradigm of 'STAT5' activation by 'JAK2' alterations in lymphoid malignancies. 'Despite' advances in our understanding of breast 'cancer,' patients with metastatic disease have poor prognoses. 'Positive' nuclear and cytoplasmic immunostaining for 'β-catenin' was evident in 21 / 22 primary colorectal adenocarcinomas ( 95 '%') and 23 / 25 cases of secondary involvement by colorectal adenocarcinoma ( 92 '%'). 'Forty-eight' male 'SD' rats were randomized into normal control ( n = 8), model ( n = 10), saline 'acupoint-injection' ( 'SAI,' n = 10), 'ABAI' ( n = 10), and 'Dexamethasone' ( 'DXM,' n = 10) groups. 'Recently,' a link between 'Slug/Snai2' and stemness has been described in mammary epithelial 'cells,' but 'EMT' master genes actual 'localization,' role and targets during mammary gland morphogenesis are not known and we focused on this basic question. 'One' critical checkpoint involves 'Notch1' signaling that instructs 'T-cell' commitment at the expense of the 'B-lineage' program. 'YY1' physically associated with 'GATA-binding' 'protein-3' ( 'GATA3)' and is required for 'GATA3' binding to the locus. 'Our' 'long-term' goal is to decipher relationships between the expression of 'ER-' and 'PR-associated' genes and breast cancer behavior to improve diagnostics and identify new molecular targets for drug design. 'We' next transplanted 'IL-4DM' skin to normal control 'mice,' and investigated effects in inflammatory reactions. 'Conditioned' media induced the expression of otic progenitor markers 'PAX8,' 'PAX2,' 'GATA3' and 'SOX2'. 'MAPK1' expression correlated with 'Th1-(IL-12A,' 'T-box' 'TF-(T-bet)),' 'Th2-(GATA' binding 'protein-(GATA)-3),' and 'IL-10' expressions. 'Specifically,' 'EZH2' regulates the composition of 'basal-like' breast cancer cell populations by promoting a '‘bi-lineage’' differentiation 'state,' in which cells 'co-express' 'basal-' and 'luminal-lineage' markers. 'Finally,' resveratrol suppressed 'CT-induced' cAMP elevation in association with decreases in 'CD80' and 'CD86' expression levels in 'BMDCs'. 'Highly' regulated expression of the negative costimulatory molecule cytotoxic 'T-lymphocyte' 'antigen-4' ( 'CTLA-4)' on 'T' cells modulates 'T-cell' activation and proliferation. 'Beyond' the 246 'TF' that appeared expressed in bovine elongating 'tissues,' we restricted our interpretation to those occurring within a list of 50 'top-ranked' genes. 'Cells' that belong to the family of innate lymphoid cells ( 'ILCs)' not only form a first line of defense against invading 'microbes,' but also play essential roles in tissue remodeling and immune pathology. 'Recently' another 'ILC' subset has been 'identified,' which is dependent on 'RORα' for its development and is dedicated to the production of the 'Th2' cytokines 'IL-5' and 'IL-13'. 'Inhaled' lidocaine inhibited 'ovalbumin-induced' airway hyperreactivity to 'methacholine,' and accumulation of 'lymphocytes,' 'neutrophils,' and eosinophils in bronchoalveolar lavage fluid 24 h after the last allergen provocation. 'IL-4' produced by 'Th2' cells can block cytokine production by 'Th1' 'cells,' and 'Th1' 'IFN-γ' is known to counterregulate 'Th2' immune 'response,' inhibiting allergic eosinophilia. 'To' investigate the role of immunological parameters in tumorigenesis of cervical cancer in women infected with high risk human papillomavirus ( 'hr-HPV),' and determine whether key findings with human material can be recapitulated in the mouse 'TC1' carcinoma model which expresses 'hr-HPV' epitopes. 'Docetaxel' promoted splenocyte responses to 'H1N1' 'antigen,' 'ConA' and 'LPS,' mRNA expressions of cytokines ( 'IFN-gamma,' 'IL-12,' 'IL-4' and 'IL-10)' and 'T-bet/GATA-3' by splenocytes. 'First,' 'Sox4' bound directly to 'GATA-3,' preventing its binding to 'GATA-3' consensus 'DNA' sequences. 'By' favouring 'GR' monomer 'formation,' 'CpdA' does not enhance glucocorticoid ( 'GC)' response 'element-driven' gene 'expression,' resulting in a reduced side effect profile as compared to 'GCs'. 'Erythropoietin' acts by binding to its cell surface receptor on erythroid progenitor cells to stimulate erythrocyte production. 'Erythropoietin' receptor expression in nonhematopoietic 'tissue,' including skeletal muscle progenitor 'cells,' raises the possibility of a role for erythropoietin beyond erythropoiesis. 'Nasal' polyposis ( 'NP)' is a 'Th2-skewed' inflammatory 'disorder,' but it is unclear what role regulatory 'T' cells ( 'T-reg)' play in disease pathology. 'Cell' surface 6-sulfated glycans play important roles in various immunological events through 'cell-to-cell' interactions. 'For' the auditory information to be 'processed,' the 'CNS' required a dedicated center for auditory 'processing,' the auditory nuclei. 'The' purpose of the present study was to determine the role of the proteasome in 'general,' as well as 'LMP7' and 'MECL1' 'specifically,' with regard to cytokine production by activated primary splenocytes. 'NPM-ALK' oncogene strongly promoted the expression of 'miR-135b' and its host gene 'LEMD1' through activation of signal transducer and activator of transcription ( 'STAT)' 3. 'Unexpectedly,' 'PMA' increased the expression of the 'GATA-3' splice variant in vivo and especially in 'vitro,' with an increase of more than 100, 0-fold in head kidney leukocytes at 24 and 48 h. 'Parental,' particularly 'maternal,' smoking increases the risk for childhood allergic asthma and infection. 'Leishmania' braziliensis antigens induced 'CD69' expression on 'CD3+CD4+' and 'CD3+CD8+' cells. 'Alcohol' consumption caused a decrease in the 'Th1' polarization and an increase in the 'Th2' response. 'Ketamine' and 'MK-801' decreased 'TH1' 'cells,' 'TH2' 'cells,' 'IFN-γ' and 'IL-4' levels but increased the ratio of 'TH1/TH2' and 'IFN-γ/IL-4' in the presence of 'PMA' and ionomycin. 'Yet,' when stimulated in vivo by 'BCG,' neonatal lung 'DCs' matured and primed adult naïve 'CD4(+)' 'T' cells toward 'Th1' as efficiently as adult 'BCG-primed' lung 'DCs'. 'Flutamide' rarely causes liver dysfunction in 'humans,' and immune allergic reactions have been suggested in some cases. 'Corticosteroids' are highly effective with a broad spectrum of 'anti-inflammatory' 'effects,' including epigenetic modulation of the inflammatory response and suppression of 'GATA3'. 'Less' clear has been the impact of vitamin 'D' on the 'pro-inflammatory' 'Th17' 'subset,' and whether and how vitamin 'D' may preferentially drive the polarization of one of the 'T' helper subsets. 'Furthermore,' the secretion of 'Th2' type cytokines was increased by 'PA' treatment in 'CMV/hGATA3' 'Tg' 'mice,' while the secretion of 'Th1' type cytokine was suppressed under the same conditions. 'Reciprocally,' 'miR-200' inhibited expression of 'Gata3,' which reversed 'EMT' and abrogated 'metastasis,' suggesting that 'Gata3' and 'miR-200' are mutually inhibitory and have opposing effects on 'EMT' and metastasis. ',' mainly secreting 'TNF-α,' 'IL-4,' and 'IL-13' and expressing 'GATA-3'. 'Active' 'MMP-2,' 'therefore,' acts as an endogenous type 2 & 'quot;conditioner"' and may play a role in the observed prevalence of detrimental type 2 responses in melanoma. 'Comparison' of result of 'EBV' polypeptide group with other 3 different cytokine stimulating groups demonstrated that 'EBV' antigen peptide had much more effects on stimulating 'CTL' generation. 'Forebrain' and midbrain 'GABAergic' neurons responded to 'ATP' ( 1 'mM),' 'L-glutamate' ( 30 'μM),' noradrenaline ( 30 'μM),' acetylcholine ( 30 'μM)' and dopamine ( 30 'μM),' with similar elevations of intracellular 'Ca(2+)([Ca(2+)](i))'. 'Paraffin-embedded' samples require higher quantity of purified 'DNA' for high performance. 'We' performed 'genome-wide' analysis to determine the general principles of 'BRG1' 'binding,' followed by analysis of specific genes to determine whether these general rules were typical of key 'T' cell genes. 'Identifying' the functional importance of the millions of single nucleotide polymorphisms ( 'SNPs)' in the human genome is a difficult challenge. 'Functional' noradrenergic transmission requires the coordinate expression of enzymes involved in norepinephrine ( 'NE)' 'synthesis,' as well as the norepinephrine transporter ( 'NET)' which removes 'NE' from the synapse. 'NET' and 'Hand2' mRNAs decreased significantly in sympathetic neurons 48 h after 'axotomy,' but 'Gata3' mRNA was unchanged. 'Only' the posterior canal crista has 'Atoh1' expressing hair cells due to incomplete recombination. 'Afferents' focus their projections on patches that express the prosensory specifying 'gene,' 'Sox2'. 'PD/AL' 'co-induction' decreased 'PD' alveolar bone loss and periodontal inflammation while experimental 'AL' parameters were unaltered. 'An' active functional interference was 'verified,' because independent 'OVA' sensitization and challenge not modulate 'PD' outcome. 'PD+AL' group presented decreased tumour necrosis 'factor-α' ( 'TNF-α),' interleukin ( 'IL)-1β,' 'interferon-γ,' 'IL-17A,' receptor activator of nuclear factor 'κ-light-chain-enhancer' of activated 'B' cells ligand and matrix metalloproteinase ( 'MMP)-13' levels in periodontal 'tissues,' while 'IL-4' and 'IL-10' levels were unaltered by 'AL' 'co-induction'. 'Acute' ethanol intoxication has the potential to alter immune reactivity by various pathways. 'And' 'GATA-3' was required for 'nTreg-to-Th2' conversion. 'Characteristically,' thymic 'NK' cells express 'CD127' and few 'Ly49' molecules and lack 'CD11b'. 'Our' work supports a relatively simple 'two-step' model that traces regulation of preplacodal development to late blastula 'stage,' resolves two distinct phases of 'Bmp' 'dependence,' and identifies the main factors required for preplacodal competence and specification. 'Overall,' the 'PyMT' induced tumors exhibited the entire gamut of phenotypes from 'ERα+/FOXA1+/GATA-3+' tumors in the early stage to 'ERα±/FOXA1-/GATA-3+' in the late stage. 'We' have investigated whether 'FOGs' and 'CTBPs' influence adipogenesis. 'Montelukast' efficaciously prevented airway inflammation and remodelling in a 'GATA-3-overexpression' antigen challenge mouse model by decreasing the 'cysLT-driven' 'Th2' cytokine cycle of amplification of airway pathologies. 'Special' 'AT-rich' binding protein 1 ( 'SATB1)' is a global chromatin organizer and a transcription factor regulated by 'interleukin-4' ( 'IL-4)' during the early 'T' helper 2 ( 'Th2)' cell differentiation. 'NO' pretreatment 'time-dependently' enhanced the association of 'GATA-3' with 'Runx2'. 'While' lactacystin inhibited 'IL-4' mRNA transcription in primary 'splenocytes,' it induced 'IL-4' mRNA in a 'concentration-dependent' manner in 'Jurkat' cells. 'Extraembryonic' tissues have various roles in 'protecting,' nourishing and patterning embryos. 'At' this 'stage,' transcription factor 'Cdx2' represses pluripotency 'genes,' thus promoting extraembryonic trophoblast fate. 'Ovarian/primary' peritoneal carcinoma and breast carcinoma are the gynaecological cancers that most frequently involve the serosal cavities. 'LCMV-triggered' 'T-bet' induction in adoptively transferred 'virus-specific' 'Th2' cells was crucial to prevent viral persistence and fatal immunopathology. 'We' have recently demonstrated that immunization with 'Salmonella' enterica 'Typhimurium' expressing the 'VapA' antigen protects mice against 'R'. 'Also,' it had been shown that certain bacteria from this environment may have 'allergy-protective' properties. lwoffii 'F78' on human 'monocyte-derived' dendritic cells especially with respect to their 'T(Helper)' cell polarization capacity was investigated by 'ELISA' and 'real-time' 'PCR' experiments as well as confocal microscopy. 'We' show that establishment of this boundary is concomitant with the induction of over a thousand genes in intestinal 'epithelium,' and these gene products provide intestinal character. 'Dissemination' of these strains may advance our understanding of 'CD' 'pathogenesis,' which in 60 '%' of patients involves the terminal ileum. 'Cytohesin' binder and regulator ( 'Cybr)' is known to regulate leukocyte adhesion and migration. 'Northern-blot' hybridisation and 'real-time' 'RT-PCR' suggested specific expression patterns of the four genes in primary 'neuroblastoma,' but did not show unequivocal results. 'In' 'addition,' remodeling of the mammary gland after parturition was impaired and 'EZH2' overexpression caused delayed involution. 'V(D)J' recombination involves the stepwise assembly of 'B' and 'T' cell receptor genes as lymphocytes progress through the early stages of development. 'Mina' specifically bound to and repressed the 'Il4' promoter. 'Microarray' analyses have revealed that forkhead box 'A1' ( 'FOXA1)' and 'GATA' binding protein 3 ( 'GATA-3)' are expressed in close association with 'ERalpha,' both encoding for transcription factors with a potential involvement in the 'ERalpha-mediated' action in breast cancer. 'NUP98-PHD' fusion prevented the 'differentiation-associated' removal of 'H3K4me3' at many loci encoding 'lineage-specific' transcription factors ( 'Hox(s),' 'Gata3,' 'Meis1,' 'Eya1' and 'Pbx1),' and enforced their active gene transcription in murine haematopoietic 'stem/progenitor' cells. 'Ink4c' deletion stimulates luminal progenitor cell proliferation at pubertal age and maintains an expanded luminal progenitor cell population throughout life. 'Two' polymorphisms of the 'CRTH2' 'gene,'-466 'T>C' and-129 'C>A' were genotyped using primer extension methods. 'PHOX2A,' a downstream target of 'Phox2b,' was found to be the sixth ranked gene from the microarray gene list. 'We' examined the genomic response of leukocytes and brain cells after ischemia in the context of 'CpG' preconditioning. 'Quercetin' is found to be the most active of the flavonoids in studies and many medicinal plants owe much of their activity to their high 'Quercetin' content. 'Thus,' viperin facilitates 'TCR-mediated' 'GATA-3' activation and optimal 'Th2' cytokine production by modulating 'NF-kappaB' and 'AP-1' activities. 'Aggressive' hepatobiliary pancreatic surgery has been associated with high complication rates. 'We' have found that 'YM-341619' 'hydrochloride,' which suppressed 'IL-4-induced' 'STAT6-dependent' reporter gene 'expression,' inhibited the differentiation of mouse spleen 'T' cells into 'Th2' cells in vitro. 'Recent' work indicates that 'Nkx6'. 'An' exceptionally high 'B19V' viral load in 'EMBs' ( 115, 91 viral 'copies/mug' nucleic 'acids),' peripheral blood mononuclear cells ( 'PBMCs)' and serum was measured in a 'DCMi' patient at initial 'presentation,' suggesting 'B19V' viremia. 'Mechanisms' of 'regulation,' 'however,' of mast cell production and maturation are still to be elucidated. 'Through' these 'factors,' 'NK-ireg' cells act as effectors of the 'down-regulation' of the immune 'response:' reconverting mature myeloid 'DC' ( 'mDC)' into 'immature/tolerogenic' 'DC,' blocking cytolytic functions on conventional 'NK' cells and inducing 'HLA-G' membrane expression on 'PB-derived' monocytes. 'Angular' head movements in vertebrates are detected by the three semicircular canals of the inner ear and their associated sensory 'tissues,' the cristae. 'Further' experiments indicated that pulmonary surfactant may facilitate the cellular uptake of gd21 by acting as an endogenous transfectant. 'The' cells are 'pluripotent,' with the potential to become hair cells and 'neurons,' the cochlear cell types whose loss causes deafness. 'Flow' cytometry and fluorescence activated cell sorting was conducted to assess the 'CD34(+)' subset composition and to obtain 'Lin(-),' 'CD34(+),' 'CD38(-)' hematopoietic stem cells. 'In' this 'study,' we first demonstrated by 'RT-PCR' analysis that human lamina propria 'T' ( 'LPT)' cells had nicotinic acetylcholine receptor ( 'nAChR),' and express alpha7 nAChR subunit universally. 'Competitive' 'EMSA' provided the evidence that 'ARE' and 'NF-kappaB-like' sites specifically interacted with placental nuclear proteins. 'To' elucidate how 'Epo' gene expression is regulated in 'vivo,' we established transgenic mouse lines expressing green fluorescent protein ( 'GFP)' under the control of a 180-kb mouse 'Epo' gene locus. 'Among' 18 known targets 'analyzed,' we identified three genes regulated by 'NKX2-5' in 'T-ALL' 'cells,' including myocyte enhancer factor 2 'C' ( 'MEF2C)'. 'Fusion' constructs with green fluorescent protein permitted subcellular detection of 'MEF2C' protein in nuclear speckles interpretable as repression complexes. 'MEF2C' consistently inhibits expression of 'NR4A1/NUR77,' which regulates apoptosis via 'BCL2' transformation. 'This' 'Th1' shift was supported by an increased 'T-bet/GATA3' mRNA ratio. 'Furthermore' they suggest that early markers of inflammatory dendritic cell and 'Th17' differentiation qualify as new target molecules for both calcitriol and highly selective 'immune-modulating' vitamin 'D' analogs. 'There' was no difference in the expression level of 'GATA-1' gene in the 'BMSCs' between normal controls and cAA group. 'The' few genes sharply 'up-regulated' between multipotent progenitors and 'Pro-T' cell stages included those encoding transcription factors 'Bcl11b,' 'TCF-1' ( 'Tcf7),' and 'HEBalt,' 'Notch' target 'Deltex1,' 'Deltex3L,' 'Fkbp5,' 'Eva1,' and 'Tmem131'. 'Strikingly,' 'FTY720' inhibited 'GATA3' and 'T1/ST2' expression which represent highly relevant markers for 'Th2' differentiation and 'Th2' effector 'function,' respectively. 'Consistently,' 'CTLA-4' blockade increased the frequency of 'Par' j 'I-specific' 'Th2' cells but not 'Th1' 'cells,' as well as 'IL-4' and 'IL-5' but not 'interferon-gamma' production. 'These' cells are generated in rhombomeres 'r1-r3' and 'r5-r7' caudal to the 'midbrain-' hindbrain organizer under the control of the fibroblast growth factors 4 and 8 and sonic hedgehog ( 'SHH)' from 'precursors,' which have produced motoneurons before. 'Concordantly,' both laboratories found that lesion formation was reduced in 'ApoE-/-' 'Ccr5-/-' mice. 'EVI1' gene is highly conserved through evolution and human gene 'EVI1' on chromosome 3 q26 encodes zinc 'fingers-containing' transcription factor. 'After' bDNA 'stimulation,' nuclear factor 'T-box' expressed in 'T' cells ( 'T-bet)' mRNA expression was conspicuously enhanced as compared to the other three groups ( 'P' & 'lt;' 0.05). 'In' this 'study,' we sought to establish the role for nAChRs in malignant transformation caused by 'NNK' and 'NNN'. donovani amastigotes efficiently infect human 'peripheral-blood' 'monocyte-derived' 'DCs'. 'i),' a mediator enhancing 'TGF-beta1' 'signaling,' and no smad7 'up-regulations'. 'Airway' remodeling is an important feature of chronic asthma that causes irreversible airflow obstruction. 'Frequent' users of smokeless tobacco ( 'ST)' have an increased risk for developing oral cancer. 'Mutants' have fewer thyrotrope cells at 'birth,' male 'Gata2-deficient' mice exhibit growth delay from 3-9 wk of 'age,' and adult mutants produce less 'TSH' in response to severe hypothyroidism after radiothyroidectomy. pneumoniae vaccine candidates requires tight control of the 'Th1' immunity elicited by the genetically delivered library of test antigens. 'Anterior' chamber associated immune deviation ( 'ACAID)' is characterized by a 'Th2' cell response. 'My' colleagues and 'I' have studied the contributions of these processes to differentiation of naïve 'CD4+' 'T-cells' to either a 'Th1' or 'Th2' phenotype. 'Other' interesting projects that have emerged as a result of our 'Th' cell differentiation studies include understanding the role of the inhibitory immunoreceptor 'B-' and 'T-lymphocyte' attenuator in the immune 'response,' as well as the role of the transcription factor 'ERM' in both 'T-cells' and spermatogenesis. 'Drugs' that prevent 'Th2-cells' from migrating into the lung 'tissue,' such as antibodies to the chemokine receptor 'CCR4' and inhibitors of the adhesion molecule 'VLA-4,' are promising for the treatment of asthma. 'A' previous study has demonstrated that 15 'd-PG' 'J2' enhanced acute lung injury induced by lipopolysaccharide ( 'LPS)' in mice. 'Transfection' experiments have revealed that 'GATA-1' and 'GATA-2' proteins are able to associate with 'AP-1' proteins. 'Freshly' prepared 'NK' cells express 'IL-2Rbeta,' 'IL-2RgammaC,' and 'IL-4Ralpha'. 'Histone' 'H3-K9/14' hyperacetylation and intergenic transcripts associated with the 'IL-4' gene locus were preserved in the absence of 'IL-4,' but those associated with the 'IL-13' gene were partially 'IL-4-dependent'. 'However,' the effect appeared attenuated compared with coculture with 'Escherichia' coli. 'In' late stages of initial 'T' cell 'activation,' the chromatin structure of the 'IL-4' locus retains condensation state. 'CD28-costimulation' selectively enhanced histone hyperacetylation of the 'IL-5' gene locus that appeared to be mediated through 'NF-kappaB' activation and subsequent 'up-regulation' of 'GATA3'. 'Similarly,' 'IL-27' induces 'T-bet' expression in primary natural killer 'cells,' but this does not result in an increase of 'IFN' gamma production or cytotoxic activity. 'By' 'contrast,' 'Six1(-/-)' mice displayed malformations of the auditory system involving the 'outer,' middle and inner ears. 'The' approach described here also illustrates the power of utilizing conserved human cDNA probes for 'cross-species' comparisons. 'Type-IV' 'zinc-finger' proteins have been extensively characterised in animals and fungi and are referred to as 'GATA' factors by virtue of their affinity for promoter elements containing this sequence. 'Hypertrophic' stimuli act through 'RhoA' 'GTPase' and 'ROCK' kinase to activate 'GATA4' in cardiac myocytes. 'Immunological' memory involves the fast recall of cytokine expression by 'T' helper ( 'Th)' lymphocytes. 'Mouse' 'GATA-2' inhibited the hypoxic induction of the 'wild-type' ( 'm3),' promoterluciferase construct but not the hypoxic induction of the mutant ( 'm4,' 5) 'promoter-luciferase' constructs. 'Pathogenic' infections lead to activation of innate immunity followed by induction of a type 1 'T' cell subset 'and,' 'therefore,' provide a good model to evaluate when 'T' cells commit to type 1 'T' cells. 'MARs' facilitate 'long-range' chromatin remodeling required for enhancer activity and have been found closely linked to several lymphoid enhancers. 'These' effects were observed in cultures driven with splenic 'APC' and 'Ag,' as well as with 'anti-CD3' and 'anti-CD28' 'alone,' indicating that 'CD4(+)' cells can also be direct targets for vitD3. 'Neither' 'c-Maf' nor 'JunB' induced 'Th2' development in 'Stat6-deficient' 'CD4+' 'T' 'cells,' in contrast to 'GATA-3'. 'Patterning' the vertebrate ear requires the coordinated expression of genes that are involved in 'morphogenesis,' 'neurogenesis,' and hair cell formation. 'In' the 'ear,' 'GATA-3' is expressed inside the otocyst and the surrounding periotic mesenchyme. 'Instead,' cAMP stimulates activation of p38 'mitogen-activated' protein kinase in 'Th2' cells. 'TGF-beta' likely inhibits 'GATA-3' expression at the transcriptional level and does so without interfering with 'IL-4' signaling. 'Both' zinc 'fingers,' 'however,' were required for 'IL-5' induction. 'Recombination' activating 'gene-1' ( 'RAG-1)' and 'RAG-2' are expressed in lymphoid cells undergoing the antigen receptor gene rearrangement. 'Since' 1988 , several families of functionally important 'T' cell transcription factors have been identified. 'Until' now the allantois has not been considered as a hematopoietic organ. 'We' show here that the elements controlling 'GATA-3' regulation can be precisely 'refined,' using transgenic 'mice,' to discrete 'cis-acting' 'domains:' within 6 kb surrounding the transcriptional initiation 'site,' separate sequences were found to control the expression of 'mGATA-3' in early muscle 'masses,' in a subset of 'PNS' 'neurons,' in the genital 'tubercle,' and in the branchial arches. 'Second,' the binding of 'AP-2' to its motif in the region from-62 to-53 led to reduced binding of 'Sp1' and 'Sp3,' and 'furthermore,' mutation of the 'AP-2' element increased promoter activity to 260 '%' in 'JEG-3' cells. 'Three' 'high-affinity' binding sites for the 'GATA' family of transcriptional regulators have been identified within the 'T-cell' receptor 'beta-chain' ( 'TCR' 'beta)' transcriptional 'enhancer,' and their functional significance has been determined in an effort to understand the 'T-cell' specificity of the enhancer more fully. 'Proteins' that recognize the core sequence 'GATA' are important regulators of 'hematopoietic-specific' gene transcription. 'Nuclear' cap binding protein complex ( 'CBC)' is a heterodimer of a small subunit ( 'Cbc2' in 'yeast)' that binds the 'm(7)G' cap and a large subunit ( 'Sto1' in 'yeast)' that interacts with karyopherins. 'Phytophthora' 'infestans,' causing late blight in 'potato,' remains one of the most devastating pathogens in potato production and late blight resistance is a top priority in potato breeding. 'The' major cytoplasmic 'deadenylase,' the 'Ccr4-Not' 'complex,' is a conserved multisubunit assembly. 'Findings' presented here clearly demonstrate that mutations in 'ABI3' can confer a 'sugar-insensitive' phenotype and help explain 'previous,' mixed reports on this topic by showing that 'ABA' and sugar insensitivity exhibit a strong positive correlation in different abi3 mutants. 'Unfortunately,' 'HBP' has 'limitations,' including questionable device validity and patient compliance. 312 'Asp/Asn' + 'Asn/Asn' decreased a 0.59 fold ( 'ORadj' = 0.59, 95 '%' 'CI' = 0.35-0.99 ',' chi2 = 3.99, 'P' & 'lt;' 0.05), when 'sex,' workage and intensity of benzene exposure were adjusted. 'Bean' genotypes reported to carry 'bc-3' resistance were found specifically to carry 'non-silent' mutations at codons 53, 65, 76 and 111 in eIF4E. 'It' was shown that 'Gapkol' with 'NCBP' ( not tanned in formalin and subjected to vacuum 'extraction)' increased reparative osteogenesis. 'NIP1' and 'NIP2' have an 'RNP' 'consensus-type' 'RNA' binding 'domain,' whereas 'NIP3' contains a unique domain of 'Arg-Glu' or 'Lys-Glu' dipeptide repeats. 'Human' neutrophil cobalamin binding protein ( 'NCBP)' is located exclusively in the neutrophil secondary granules. 'Nevertheless,' 'CBP20S' does bind 'mRNA,' is localized to an active transcription site and redistributed to nucleolar caps upon transcription inhibition. 'The' levels of 'primary-let-7a' ( 'pri-let-7a)' are not affected by 'menin;' 'however,' the levels of mature 'let-7a' are substantially decreased upon 'Men1' excision. 'SLBP' preferentially associates with the 'CT' complex of histone 'mRNAs,' but not with the 'eIF4E-depedent' translation ( 'ET)' complex. 'Both' 'Aly' and 'THO' function in linking 'UAP56' to the 'cap-binding' protein 'CBP80'. 'Here,' our microarray analysis reveals that the level of 'cyclin-dependent' kinase inhibitor 1 'A' ( 'CDKN1A;' also known as 'Waf1/p21)' mRNAs increases in cells depleted of cellular 'NMD' factors. 'Targeting' the 'cap-binding' pocket of eIF4E should represent a way to inhibit all the eIF4E cellular functions. 'NMD' largely functions to eliminate mRNAs that prematurely terminate 'translation,' although 'NMD' also contributes to proper gene 'control,' and it targets 'CBC-bound' mRNPs. 'These' 'results,' together with our previous demonstration of the association of splicing factors and 'A-to-I' editing enzymes with lnRNP 'particles,' support the view that the lnRNP particles are the nuclear 'pre-mRNA' processing machine. 'Temperature-sensitive' alleles have defects in the export of mRNA out of the nucleus ( 1). 'Yeast' strains lacking the yeast nuclear 'cap-binding' complex ( 'yCBC)' are 'viable,' although impaired in growth. 'Both' 'Npl3p' and 'Hrp1p' fail to exit the nucleus in cells lacking 'Hmt1p,' and overexpression of 'Hmt1p' enhances 'Npl3p' export. hnRNP 'F' and 'CBC' bind independently to 'RNA,' but hnRNP 'F' binds preferentially to 'CBC-RNA' complexes rather than to naked 'RNA'. 'Cryolesion' induced massive muscle degeneration associated with inflammatory infiltrate. 'Activated' 'MSCs' proliferate and differentiate to repair damaged fibers or 'self-renew' to maintain the pool and insure future regeneration. 'Avian' broilers have been genetically selected based on their high growth velocity and large muscle mass. 'I-mfa' ( inhibitor of the 'MyoD' family 'a)' is a transcription modulator that binds to 'MyoD' family members and inhibits their transcriptional activities. 'Heterologous' expression of 'TRPC1ε' in 'HEK293' cells revealed that it is unique among all known 'TRPC1' isoforms in its ability to amplify the activity of the 'Ca(2+)' 'release-activated' 'Ca(2+)' ( 'CRAC)' 'channel,' mediating 'store-operated' currents. 'Furthermore,' 'Zic3' 'co-precipitated' with 'Tcf1' ( a 'β-catenin' 'co-factor)' and 'XIC' ( 'I-mfa' domain containing factor required for dorsoanterior 'development)'. 'These' studies highlight that the multivalent nature of the 'Rev' 'NLS' for different import receptors enables 'Rev' to adapt its nuclear trafficking strategy. 'Pem' transcripts are abundant in 7-and 8-day mouse 'embryos,' but decrease precipitously thereafter. 'DBA' typically leads to a hypoplastic anemia that becomes apparent during the first year of 'life,' and standard treatment includes steroids or red blood cell 'transfusions,' each modality having attendant side effects. 'DBA-mutant' 'embryonic,' induced 'pluripotent,' and hematopoietic stem cells exhibit growth abnormalities that can be corrected by 'DNA' gene 'transfer,' suggesting the possibility of ex vivo autologous gene therapy. 'These' 'TFs' act in a combinatorial manner to bind 'sequence-specific' 'DNA' within a promoter region to regulate 'lineage-specific' gene 'expression,' either as activators or as repressors. 'PRMT1' expression enhanced the production of hemoglobin and the erythroid surface marker glycophorin 'A,' and also 'up-regulated' several key transcription 'factors,' 'GATA1,' 'NF-E2' and 'EKLF,' which are critical for 'lineage-specific' differentiation. 'Here' we report that 'GATA-1,' 'SCL,' and 'Klf1' form an erythroid core transcriptional network by 'co-occupying' & 'gt;300' genes. 'Higher' eukaryotes have evolved elegant mechanisms by which committed 'gene-expression' states are transmitted through numerous cell divisions. 'Through' 'protein/protein' 'interactions,' 'NF-Y' bound at the 'CCAAT' motif recruited 'MZF1' and 'GATA-2,' but not 'Sp1' and 'GATA-1,' and stabilized their binding to the neighboring 'GTGGGGA' and 'GATA' sites to assemble a novel 'LTR' enhancer 'complex,' 'NF-Y/MZF1/GATA-2'. 'Co(2+)' was used as a spectroscopic probe in a series of competition titrations to determine the affinity of 'Co(2+)' and 'Zn(2+)' for the 'C-terminal' finger from chicken 'GATA-1' and the double finger from human 'GATA-1' ( referred to in this report as 'CF' and 'DF)'. 'SCL' and 'LMO-2' act synergistically to expand the blood island when overexpressed in whole embryos. 'We' show that this specificity involved two 'cis-acting' sequences. 'Lead' ( 'Pb)' and cadmium ( 'Cd)' are heavy metal toxins that cause many pathophysiologic 'effects,' including anemia. 'Agents' that target the two highly conserved 'Zn' fingers of the human immunodeficiency virus ( 'HIV)' nucleocapsid p7 ( 'NCp7)' protein are under development as antivirals. 'The' diagnosis of 'CEP' is supported by the biochemical findings of markedly decreased uroporphyrinogen ( 'URO)-synthase' activity in erythrocytes 'and/or' markedly increased levels of urinary uroporphyrin 'I' and coproporphyrin 'I' isomers. 'CCAR1' and 'CoCoA' synergistically enhanced 'GATA1-mediated' transcription from the 'γ-globin' promoter in 'MEFs'. 'In' concert with the transacting factor 'GATA1,' 'KLF1' modulates the coordinate expression of the genes encoding the 'multi-enzyme' heme biosynthetic pathway during erythroid differentiation. 'Immunofluorescence' assay showed that 'GF1' had no effect on melanosome 'transport,' but significantly induced dendrite retraction. 'Randomised' controlled trials and 'quasi-randomised' controlled trials comparing allogeneic hematopoietic stem cell transplantation with each other or with standard therapy ( regular transfusion and chelation 'regimen)'. 'These' are valuable procedures for couples at 'risk,' so that they can be offered options to have healthy offspring. 'Moreover' 894 & 'nbsp;TT S/S' and 'β(0)/S' patients tended to have higher hematocrit than 894 & 'nbsp;GG' and 'GT' ones. 'Four' globins have been identified in rodent and human brains. 108 'C>A)' leading to the premature stop codon. 'We' suggest that this disorder could result from a disturbed interaction between the abnormal 'α-Hb' chains and 'AHSP'. 'Combinations' of 'MIMs,' exemplified by the 'SCL/LMO2' 'complexes,' which have variable content and binding 'sites,' explain how individual regulators can have different targets in 'HSCs' and erythroid cells and possibly also how 'HSCs' maintain stem cell functions while expressing 'lineage-affiliated' genes at low 'level,' 'so-called' 'multi-lineage' priming. 'In' a heterologous transcriptional system in which the upstream regions of oIFNtau were inserted in front of simian virus 40 ( 'SV40)' 'promoter,' the regions between bases-654 and-555 were determined as being the enhancer region required for 'oIFNtau-SV40-CAT' transactivation. 'In' addition and in contrast to signaling in 'Mo7e' and 'BM6' cell 'lines,' in 'FDC2-ER' cells 'SCF' and 'Epo' each were shown to rapidly activate 'Pim' 1 gene expression. 'Murine' 'C/EBP' alpha has a 'C/EBP' binding site in its own promoter. 'Gel' filtration chromatography confirms the 'differentiation-dependent' binding and shows that it correlates with the assembly of a complex also containing the key megakaryocyte transcription factors 'GATA-1' and 'Friend' of 'GATA-1' ( 'FOG-1)'. 'Seven' of 11 'APL' cases expressed 'EVI-1' 'RNA' detected by 'RNA' 'PCR' at 'diagnosis,' and expression was detected in two additional cases after treatment with 'all-trans' retinoic acid ( 'ATRA)'. 'Compound' 'C' remarkably suppressed the 'IL-1-induced' phosphorylation of 'IκB'. 'Especially' noncoding conserved elements of paternally expressed genes are exceptionally 'G+C' and 'CpG' rich. 'Prior' work has indicated that 'BMP' signals act in concert with 'FGF8,' 'WNT11' and 'WNT' antagonists to induce the formation of cardiac tissue in the vertebrate embryo. 'Resveratrol,' a polyphenolic phytoalexin found in grapes and 'wine,' has been reported to act as an agonist at the estrogen receptor. 'TBP,' 'TFIIB,' 'TAFII55,' 'Sp1,' and 'E1A)' has suggested that these interactions are important for determining which particular function of 'YY1' is displayed at a specific promoter. 'Two' groups of 'proteins,' previously known to function as corepressors and 'coactivators,' that now seem likely to modulate 'YY1\'s' 'functions,' are the histone deacetylases ( 'HDAC)' and histone acetyltransferases ( 'HAT)'. ( 'iii)' 'There' is evidence that 'UCRBP' acts as a phosphoprotein. 20135 and found to reduce the effects of 'LPS-induced' inflammation. 'The' cells on the titanium surface produced excessive 'ROS' and decreased the activity of 'Cu/Zn' 'SOD' and 'Mn' 'SOD'. 'Transfection' assays with luciferase 'reporter-constructs' identified a core promoter region within 146 bp immediately upstream of the transcriptional start site of zebrafish 'CTCF' that is located at a highly conserved 'YY1/Initiator' element. 'Sequencing' of chromatin obtained in 'chromatin-immunoprecipitation' ( 'ChIP)' assays carried out with αYY2 serum allowed us to identify a limited number of chromatin targets for 'YY2'. 'Exome' and targeted sequencing revealed that 14 of 43 insulinomas harbored the identical somatic mutation in the 'DNA-binding' zinc finger of the transcription factor 'Yin' 'Yang' 1 ( 'YY1)'. 'Both' gene products are involved in key pathways regulating insulin secretion. 'The' suppressive effects of 'IFN-γ' on the mRNA expression of 'α-globin' and 'ζ-globin' were absent in cells expressing 'DN' 'c-Jun'. 'The' most common 'PRS-Plus' malformations involved the musculoskeletal and ocular systems. ( 32) 'Recently,' transientness has also been reported in acute myeloid leukemia patients with germline trisomy 21 'mosaicism,' and even in cases with somatic trisomy 21, with or without 'GATA1' mutations. 'Protective' vaccination induces 'self-healing' of otherwise fatal 'blood-stage' malaria of 'Plasmodium' chabaudi in female 'Balb/c' mice. 'Women' heterozygous for a 'GATA1' or 'TSR2' pathogenic variant have a 50 '%' chance of transmitting the pathogenic variant in each 'pregnancy:' males who inherit the pathogenic variant will be 'affected;' females who inherit the pathogenic variant will be carriers and will usually not be affected. 'Metal' 'ion-containing' macromolecules have fundamental roles in essentially all biological processes throughout the evolutionary tree. 'In' 'turn,' 'FOG-1' displaces 'pRb/E2F-2' from 'GATA-1,' ultimately releasing 'free,' proproliferative 'E2F-2'. 'Factors' in cell proliferation were obviously suppressed after 3-day treatment with histone deacetylase 'inhibitor,' valproic acid. 'Simulated' microgravity treatment of the cells resulted in 'down-regulated' 'GATA-1,' 'F-actin,' 'β-tubulin' and vimentin mRNA expressions and 'up-regulated' mRNA expressions of 'GATA-2' and 'Ets-1,' and reduced 'F-actin,' 'β-tubulin' and vimentin protein expressions. 'Subsequent' evaluation ultimately led to a diagnosis of 'AMKL'. 'Recombinant' carp 'Kitla' alone induced limited colony 'formation,' whereas a combination of 'Kitla' and 'Epo' dramatically enhanced erythroid colony formation and colony cell 'growth,' as well as stimulated the formation of 'thrombocytic/erythroid' colonies expressing not only erythroid markers but also thrombocytic 'markers,' cd41 and 'c-mpl'. 'Insulin-like' peptide mediated body size plasticity in 'Drosophila' melanogaster has been reported. 'We' found that 'CSA' blocked 'JAG1,' but not 'Dll4' mediated 'Notch1' 'NICD' cleavage in transfected 293 'T' cells and decreased 'Notch' signaling in zebrafish embryos. 'Important' strides have been made with respect to the clinical significance of 'NFE2,' linking this transcription factor to hematological disorders such as polycythemias. 'He' received less intensive 'chemotherapy,' and he is now 6 & 'nbsp;years' old in complete remission. 'Congenital' myeloproliferative disorders and transient leukemic disorders have been described in the perinatal period in infants with trisomy 21 ( 'Down' 'syndrome)'. 'To' address this 'issue,' we 'knocked-down' 'Dok2' mRNA in mouse erythroleukemia cells which highly express 'Dok2' intrinsically. 'NB4' and 'MV-4-11' express high levels of 'CCAAT/enhancer-binding' 'protein-alpha' ( 'CEBPα)' and differentiate from myeloblasts to 'pro-monocytes' and 'myeloblasts,' respectively. 'Herein,' we characterize transgenic 'C57BL/6' 'mice,' in which the 'Cebpa' enhancer and 845-bp promoter regulate a hCD4 reporter. 'Bone' marrow transplantation reproduced these phenotypic changes in 'wild-type' 'recipients,' demonstrating that the effect of 'Stat1' is 'cell-intrinsic' and does not require a 'Stat1-deficient' microenvironment. 'GATA1-related' cytopenia is characterized by thrombocytopenia 'and/or' anemia ranging from mild to severe. 'To' clarify the role of 'HDACs' in 'erythropoiesis,' 'expression,' activity and function of class 'I' ( 'HDAC1,' 'HDAC2,' 'HDAC3)' and class 'IIa' ( 'HDAC4,' 'HDAC5)' 'HDACs' during in vitro maturation of human erythroblasts were compared. 'Pias1' disruption caused the abnormal expression of 'lineage-associated' genes. 'Binding-site' mapping using 'ChIP-Seq' indicates that most 'DNA-bound' 'Gata1' and 'Tal1' proteins are contained within higher order complexes ( 'Ldb1' 'complexes)' that include the nuclear adapters 'Ldb1' and 'Lmo2'. 'Depleting' them severely impaired erythrocyte 'maturation,' inhibiting cell size reduction and subsequent enucleation. 'ΔdblGATA' basophils responded poorly ex vivo to stimulation with 'IgE' plus antigens compared with 'wild-type' basophils as assessed by degranulation and production of 'IL-4' and 'IL-6'. 'Treatment' of the 'Meg-01' cells with the histone deacetylase inhibitor valproic acid resulted in 'down-regulation' of both 'GATA1' and 'Bcl-xL' and significantly enhanced 'ara-C' sensitivity. 'Normal' 'ERYs' required exposure to the glucocorticoid dexamethasone ( 'Dex)' for 'expansion,' while 'PV-derived' 'ERYs' expanded in the absence of dexamethasone. 'To' examine the hypothesis that the 'Hsa21' 'ETS' transcription factor 'ERG' cooperates with 'GATA1s' in this 'process,' we generated 'double-transgenic' mice expressing hERG and 'Gata1s'. 'Substitutions' that disrupt 'FOG1' cofactor binding impair both gene activation and repression and are associated with pronounced clinical phenotypes. 'Myofibroblast-like' 'CAFs' and induced normal mammary fibroblasts promoted invasion of breast cancer cells by distinct 'mechanisms,' consistent with their distinct patterns of 'TF' activation. 'Commensurately,' 'HSC' and 'megakaryocyte-erythroid' progenitors show higher 'clonogenicity,' with increased 'megakaryocyte,' 'megakaryocyte-erythroid,' and replatable blast colonies. 'Nucleosome' shifting has been demonstrated to facilitate 'TAL1' but not 'GATA-1' binding to regulate target gene expression. 'Importantly,' the red cells exhibited increased reactive oxygen species accumulation. 'Pre-B-cell' leukemia homeobox interacting protein 1 or human 'PBX1' interacting protein ( 'PBXIP1/HPIP)' is a 'co-repressor' of 'pre-B-cell' leukemia homeobox 1 ( 'PBX1)' and is also known to regulate estrogen receptor functions by associating with the microtubule network. 'Transcriptional' enhancers binding 'chromatin-remodeling' and modifying complexes may play a role in shielding transgenes from repressive chromatin effects. 'In' 'contrast,' several frequent changes were identified in the 'DS-ALL' 'cases,' which harbored 82 imbalances ( 30 gains and 52 'losses)' and four pUPDs. 'Understanding' platelet biology has been aided by studies of mice with mutations in key megakaryocytic transcription factors. 'Repetitive' sequences consist of & 'gt;50%' of mammalian genomic 'DNAs' and among these 'SINEs' ( short interspersed nuclear 'elements),' e. 'Phylogenetic' and conserved synteny studies showed that stat1b and stat1a arose as duplicates in the teleost genome duplication ( 'TGD)' and clarified the evolutionary origin of 'STAT1,' 'STAT2,' 'STAT3,' 'STAT4,' 'STAT5A,' 'STAT5B' and 'STAT6' by tandem and genome duplication. 'Later' liver proerythroblasts express low levels of 'γ-globin,' while adult marrow proerythroblasts express only 'β-globin' transcripts. 'FlnA-null' platelets have decreased expression and altered surface distribution of 'GPIbalpha' because they lack the normal cytoskeletal linkage of 'GPIbalpha' to underlying actin filaments. 'Leukemia' associated 'AML1-ETO' strongly suppressed an 'ETO' promoter reporter in 'erythroid/megakaryocytic' cells. 'So' while increased 'MK' number in 'GATA-1' deficient mice likely contributes to the high bone mass 'phenotype,' we propose that the increased longevity of this lineage also plays a role. 'Epitope' tags have often been used as more reliable alternatives. 'By' examining the composition of 'GATA-1-associated' protein complexes in a conditional erythroid rescue system as well as through the use of tiling arrays we detected the 'SCL/TAL1,' 'LMO2,' 'Ldb1,' 'E2A' complex at all positively acting 'GATA-1-bound' elements examined. 'Indeed' the virus has been implicated as the causative or the precipitating agent of several autoimmune disorders including rheumatoid 'arthritis,' systemic 'lupus,' antiphospholipid 'syndrome,' systemic sclerosis and vasculitides. 'Two' conserved 'miRNAs,' miR 144 and miR 451 , emerged as direct targets of the critical hematopoietic transcription factor 'GATA-1'. 'NLI/Ldb1,' a widely expressed nuclear 'factor,' is a potential mediator of 'long-range' interactions. 'Administration' of prohibited substances to enhance athletic performance represents an emerging 'medical,' 'social,' ethical and legal issue. 'A' previous investigation detailed the pathology of platelets in a family with the 'X-linked' 'GATA-1' 'G208S' mutation causing dyserythropoiesis and megathrombocytopenia. a 'I-kappa-B-alpha,' 'IKBalpha)' and toll interacting protein ( 'TOLLIP),' both inhibitors of 'inflammation,' along with downregulated expression of the immunoregulatory transcription factor 'GATA' binding 'protein-1' ( 'GATA1)' is consistent with the maintenance of intestinal homeostasis. 'Thus' the oncogenic role of trisomy 21 in the more common sporadic childhood leukemias may be revealed through the investigations of the relatively rare leukemias of 'DS'. 'Children' with 'DS' and leukemia are more sensitive to some chemotherapeutic agents such as methotrexate than other children which requires careful monitoring for toxicity. 'Within' eight target 'loci,' we tested 75 noncoding segments by reporter gene assays in transiently transfected human 'K562' cells 'and/or' after 'site-directed' integration into murine erythroleukemia cells. 'DS-TL' neonates have a approximately 15 '%' risk of developing potentially fatal liver disease and show & 'lt;10%' incidence of hydrops fetalis. 'Nucleosome' depletion at 5 '\''-'HS4' was dependent on interaction of the insulator protein 'CCCTC-binding' factor ( 'CTCF)' and was required for enhancer blocking. 'They' also developed airway hyperreactivity ( 'AHR)' to 'methacholine,' demonstrable as increased transpulmonary resistance and decreased compliance. 'We' show here that the 'Bmp' receptor 'lost-a-fin/alk8' is required for rostral pu. 'Interestingly,' in embryos with severely reduced 'Scl' 'levels,' erythroid progenitors expressing gata1 and embryonic globin developed. 'AKT' serine threonine kinase phosphorylates 'GATA-1S310' in vitro and in erythroid cells and enhances 'GATA-1' transcriptional activity. 'Immunostaining' for 'PCNA' and enhanced green fluorescence protein ( 'eGFP)' was performed in 'wild-type' and 'fli1-eGFP' ( endothelial 'marker)' and 'gata1-eGFP' ( erythroid cell 'marker)' transgenic fish. 'Oncogene' products associated with acute leukemias are often transcription factors while tyrosine kinases and antiapoptotic proteins are more commonly activated or overexpressed in chronic leukemias and in lymphomas. 'Anthracycline' antitumor drugs induce erythroid differentiation of the 'K562' erythroleukemic cell line at subtoxic concentrations. 'We' conclude that the nature of the amino acid substitution at position 218 of the 'Nf' of 'GATA1' is of crucial importance in determining the severity of the phenotype in 'X-linked' macrothrombocytopenia patients and possibly also in inducing skewed 'X' inactivation. 'Jak2' then mediates the phosphorylation of receptor tyrosine sites and the recruitment of 25 or more 'Src' homology 2 'domain-encoding' proteins and associated factors. 'To' elucidate regulatory mechanisms of the gata1 'gene,' we have used zebrafish. 'Hydroxyurea,' a small organic 'compound,' has been successfully used to treat sickle cell anemia and 'beta-thalessaemia'. 'GATA4' is a transcriptional activator of 'cardiac-restricted' promoters and is required for normal cardiac morphogenesis. 'Under' the same 'conditions,' 'AZT' inhibited the 'beta-globin' chain synthesis by approximately 60 '%' as compared with the control. 'Comparison' of the 'HS5' sequences of 'mouse,' 'human,' and galago revealed two extensively conserved 'regions,' designated 'HS5A' and 'HS5B'. 'Overexpression' of the transcription factor 'GATA-1' in mast cells caused elevated 'T1' synthesis. 'Sequence' analysis of a 2.7-kb 'DNA' fragment upstream of the 'TR2' orphan receptor translation start codon unveiled several potential 'cis-acting' 'elements,' such as 'AP-1,' 'HNF-5,' 'GATA1' binding 'sites,' and 'GC' boxes. 'AC)' carrying an activated 'v-Ha-ras' oncogene fused to the embryonic 'zeta-globin' promoter develops an array of spontaneous epithelial and mesenchymal neoplasms. 'The' abolishment of 'NF-E2' p45 with 'NF-E2' antisense oligomers inhibited 'TPO' plus 'K252a-induced' polyploidization. 'The' cloning efficiency of the 'GATA-1-expressing' fibroblasts was maintained but their 'S' phase was greatly elongated and their 'G1' and 'G2/M' phases were 'reduced,' impairing substantially their proliferation. 'Steroid' hormones regulate diverse biological 'functions,' including programmed cell death ( 'apoptosis)'. 'Indeed,' 'ACLA' induces an increase either in the binding capacity of 'GATA-1' and 'NF-E2' or in the accumulation of erythropoietin 'receptor,' 'GATA-1' and 'NF-E2' transcripts. 'Protein-DNA' binding studies suggested that 'Sp1' and two other 'CCGCCC' binding proteins from erythroid and 'non-erythroid' cells could bind to the 'Sp1' binding motif. 'High-dose' estrogen administration induces anemia in mammals. 'Concomitantly,' an increase in protein capable of binding to the 'GATA' motif was detected. 'Six' transgenic lines expressed the transgene and displayed a clear oncogenic phenotype. 'The' lack of a block in terminal megakaryocyte differentiation was shown by the in vivo production of platelets expressing the 'ES' 'cell-derived' 'GPI-1C' isozyme. 2 region the position of the breakpoint in both cell lines was suggested as 'follows:' 'Xpter-->Xp11'. 'Mut-GATA1' clones expressed the 'A' 'gamma*' mRNA at the same level as 'WT' clones in both uninduced and induced cells. 'Protein' 'B,' associated with 'epsilon-globin' silencer activity in 'vitro,' required an intact epsilon 'GSM' sequence for binding. 'Quercetin,' 'apigenin,' and luteolin completely protected against 'IL-1beta-' and 'IFN-gamma-mediated' cytotoxicity in 'RIN' cells. 'These' mice have thyrotrope hypertrophy and hyperplasia and develop thyrotrope adenoma. 'Thus,' 'Tceal5' may act as a 'proto-oncogene'. 'The' 'MED1' subunit of the 'Mediator' transcriptional coregulator complex is a nuclear 'receptor-specific' coactivator. 'Hyperosmolarity' decreases 'claudin-2' expression in renal tubular epithelial 'cells,' but the molecular mechanism remains undefined. 203 'G>A,' causing the protein change 'NP_005655'. 'ΔNp63' variants cannot induce apoptosis but can act as dominant negative inhibitors to block the function of 'TAp53,' 'TAp73,' and 'TAp63'. 'MDSC-induced' 'L-selectin' loss occurs through a 'contact-dependent,' 'post-transcriptional' mechanism that is independent of the major 'L-selectin' 'sheddase,' 'ADAM17,' but results in significant elevation of circulating 'L-selectin' in 'tumor-bearing' mice. 'They' completed the 'Brief' 'Resilience' 'Scale,' a 'Coping' 'Strategies' 'Questionnaire,' the 'Posttraumatic' 'Growth' 'Inventory' ( 'PTGI),' and provided demographic and 'work-related' information. 'Different' 'stimuli,' acting at sites remote from the heart ( remote 'conditioning),' activate molecular 'self-defense' mechanisms at the target organ heart as well as in other parenchymal organs. 'Systematic' reviews have clearly formulated 'questions,' can identify relevant studies and appraise their quality and can summarise evidence and reasoning with an explicit methodology. 'Social' interventions targeted at people with severe mental illness ( 'SMI)' often include volunteers. 'However,' the families often doubted their personal judgement and relied on mental health workers to act as safety net. 'A' range of inhibitors of novel 'PKC' isoforms prevent phorbol 'ester-induced' respiration. 'Wheat' stem 'rust,' caused by 'Puccinia' graminis f. 'Last' january the 'Guardian' reported that '\'' the 'NHS' is in an impossible situation which endless reforms have failed to 'address\''. 'Using' chemical genetic and optogenetic 'tools,' we demonstrate that the association of 'ECT2' with the plasma membrane during anaphase is required and sufficient for cytokinesis. 'Local' membrane targeting of 'ECT2' leads to unilateral 'furrowing,' highlighting the importance of local 'ECT2' activity. 'Studies' were excluded if they were conducted outside the 'United' 'States,' focused on recent immigrant 'populations,' or 'didn\'t' have an 'English-language' abstract. 'Interestingly' 'Mael' was essential for 'Myc/Ras-induced' 'transformation,' and its overexpression inhibited 'Ras-induced' senescence. 'Though' monetary incentives are pivotal in traditional economic 'theory,' biological and psychological theories ascribe less significance to monetary incentives and suggest alternative drivers for motivation. 'Empathy' ability has strong relationships with cognitive and emotional functions. 'We' think the consideration of three different stages in the educational process may be useful to engineers when they act as educators. 'Constituents' most likely to discourage respondents from wanting to smoke were 'ammonia,' 'arsenic,' 'formaldehyde,' hydrogen 'cyanide,' lead and uranium. 'The' modulation exerted by glucocorticoids in physiological responses to stressors is essential for maintaining 'short-term' homeostasis. 'Due' to ongoing horizontal 'consolidation,' hospital markets in the 'Netherlands' have become highly concentrated. 'Many' therapists have reservations and uncertainties regarding an appropriate therapy for refugees due to a lack of experience. 'This' means that only a fraction of the young refugees with 'trauma-related' disorders find an ambulatory therapist. of 'Chemical' 'Substances' ( 'ARECS)\'' or the new '\'' 'Biocidal' 'Product' 'Act\'' must not only address the blind areas in the management system for chemical and product 'safety,' but also prevent a second 'HDD'. 'Like' everyone who 'cares,' we search for an answer to the reason why a fellow human could carry out such a senseless act as the 'Soho' bombing. 'Yet' a scrutiny report by the 'House' of 'Lords' concluded this legislation was 'under-used' with a lack of knowledge among professionals regarding applying the legislation in practice. 'Generally,' under 'Health' 'Insurance' 'Portability' and 'Accountability' 'Act,' personal representatives have the same authority to receive information that patients would otherwise have. 'At' 'autopsy,' the sole was wedged in the esophagus causing a choking ab extrinseco. 'miR-33a' overexpression suppresses prostate cancer cell survival and metastasis. 'Sequence' alignments have indicated that 'Apserpin-3' might regulate the melanization reaction via inhibiting 'prophenoloxidases-activating' 'protease(s)' in plasma. 'Distal' vessel calcification has been shown to be a major factor in causing 'CHI'. 'The' following important principles were followed during the use of 'OAS' for 'CHI:' ( 1) 'ACT' was therapeutic ( '~250s);' ( 2) 'Gentle' wire 'manipulation;' ( 3) 'Utilization' of a small 'OAS' crown ( 1.25 'mm);' ( 4) 'Aggressive' vasodilator 'use-given' through the exchange 'catheter;' ( 5) 'Angioplasty' balloon was matched to the size of the vessel and long and low pressure inflations were completed. 'Initially,' the 'FDA' authority was restricted to issues of safety and only later did the documentation of efficacy become part of the review process required for approval. 'Self-efficacy' was a predictor of fatigue but did not act as moderator. 'Mosquitoes' act as vectors of key pathogens and parasites. 'Plant' essential oils have been recognized as important sources of 'biopesticides,' which do not induce resistance and have limited toxic effects on human health and 'non-target' organisms. 'Our' results suggest that 'CaV1'. 'Physical' inactivity is common in persons with multiple sclerosis ( 'MS),' but there is very little known about the pattern and predictors of changes in physical activity over time. 'Private' 'schools,' which serve about five million 'US' children and 'adolescents,' may be falling short in providing quality 'PE'. 'Nurse' executives and their nursing leadership colleagues must lead with evidence in hand to create infrastructures that support true 'integration,' 'optimization,' and engagement of all members of the provider team to better serve our patients and communities. 'Therefore,' the specific sensory features of cues may differentially contribute to responding and ensure behavioral flexibility. 'Synthesized' nanostructures were characterized hexagonal wurtzite structure of size '~24' nm by 'UV-visible,' 'XRD,' 'FTIR' and 'TEM'. 'Malodorous' pollution has previously been associated with aggravated physical and psychological 'health,' and in persons affected by a 'trauma,' an 'incidence-related' odour can act as a traumatic reminder. 'Allopurinol,' a competitive xanthine oxidase 'inhibitor,' in addition to reducing serum uric acid 'levels,' can act as a free radical scavenger. 'Using' our 'AdRGD-PG' adenovector 'platform,' we show here for the first time that in situ gene transfer of p19Arf and 'interferon-β' ( 'IFNβ)' in the 'LLC1' mouse model of lung carcinoma acts as an immunotherapy. 'A' 'REMS' is a required risk management plan that uses tools beyond the package insert. 'An' implementation system is required for an 'REMS' that includes the 'ETASUs'. 'Improving' assessment guidance and feedback for students has become an international priority within higher education. 'Aspirin' has the potential to acetylate other 'amino-acid' 'side-chains,' leading to the possibility that 'aspirin-mediated' lysine acetylation could explain some of its 'as-yet' unexplained drug actions or 'side-effects'. 'Total' nominal 'US' health care spending increased 5.8 & 'nbsp;percent' and reached '$3'. 'It' provides a 'closed-form' control solution. 'OPRK1' expression in 'VTA' correlated negatively with 'sexual/agonistic' 'behaviors,' consistent with past studies showing kappa receptors in 'VTA' to inhibit sociosexual behaviors. 'Near-patient' surfaces act as reservoirs of microbial 'soil,' which may contain pathogens. 'Mitochondrial' oxidative damage has long been known to contribute to damage in conditions such as 'ischaemia-reperfusion' ( 'IR)' injury in heart attack. 'TM' siRNA depressed the 'PMA-induced' increase of 'p21(Cip1/WAF1)' via 'ERK1/2-NF-kB' p65 signaling. 'All' clinically tested 'DORAs' induce and maintain 'sleep:' 'suvorexant,' recently registered in the 'USA' and 'Japan' for 'insomnia,' represents the first hypnotic principle that acts in a completely different manner from the current standard medications. elderly 'patients)' where 'REM-associated' loss of muscle tone may promote an elevated risk of falls. 'Promotional' material suggests that balanced sleep is indeed induced by 'MIN-202,' whereas in volunteers 'MK-1064' has been reported to act similarly to 'DORAs'. 'Telephone' interviews were 'recorded,' 'de-identified,' transcribed and thematically analysed. 'Cancer' 'Information' and 'Support' nurses internationally act as expert 'navigators,' educators and compassionate communicators who '\'' listen between the 'lines\'' to enable callers to better understand and contextualise their situation and discuss it with their healthcare team and family and friends. 'Resolving' this issue is particularly important given recent clinical trials showing that 'anti-CGRP' monoclonal antibodies can reduce and even prevent migraine attacks. 'The' physiological role of the herein identified eukaryotic 'D-ribulokinase' remains 'unclear,' but we speculate that 'S'. 'GPR119' and 'TGR5' provide more than additive 'GLP-1' secretion both ex vivo and in vivo in mice. 'Synthetic' progestins act as endocrine disrupters in fish but their risk to the environment is not sufficiently known. 'President' 'Obama' has indicated that the law has accomplished many of its 'goals,' including increasing 'accessibility,' 'affordability,' and quality of health care. 'Using' this 'approach,' we achieve sufficient retardance to act as a 'quarter-wave' plate. 'To' this 'end,' we performed a systematic visual screen using the yeast 'Saccharomyces' 'cerevisiae,' and uncovered three uncharacterized proteins whose loss affected targeting. 'Moreover,' we proposed 'that,' because 'DCs' are likely to be exposed to multiple 'stimuli,' the activity of 'PAC' may synergise with other bioactive molecules that have 'anti-inflammatory' 'activity,' e. 'LncRNAs' that act as oncogenes and 'lncRNA-regulating' transcription factors provide novel targets for 'anti-lung' cancer therapeutics. 'Interestingly,' we observed that 'IE1' expression did not affect preSUMOylated 'PML,' 'however,' it clearly prevented de novo 'SUMO' conjugation. 'Cushion' plants act as 'pioneers,' by starting the successional processes that continue with shrubs and tussocks. 'Tussock' grasses have sometimes been found to be capable of creating microhabitat patches independently. 'Most' 'PSK' systems use a cytoplasmic 'toxin,' but the external toxins of bacteriocins also have a 'PSK-like' effect. 'Recommendations' for enhancing the recovery orientation of supportive housing and implications for the design of the homeless service system are discussed. 'The' study of enzyme function often involves a 'multi-disciplinary' approach. 'Dioxin-like' chemicals act on the aryl hydrocarbon receptor ( 'AhR),' 'polymorphisms,' and mutations of 'AhR-related' gene may exert pathological influences on sexual differentiation of the 'brain,' causing autistic traits. 'Descriptive' statistics were used to report survey results. 'Increasing' evidences have demonstrated that the dysregulation of long 'non-coding' 'RNAs' ( 'lncRNAs)' may act as an important role in tumor progression. 'Proprotein' convertase 'subtilisin/kexin-6' has been identified as a primary enzyme that converts zymogen corin to an active protease. 'We' investigated the biotransformation of 79 structurally different 'MPs' by the 'inhibitor-treated' and untreated sludge communities. 'However,' alkali 'pre-treatment' ( 35.3 'gNaOH/kgTS)' by itself and alkali ( 157 'gNaOH/kgTS)' and ultrasound ( 27, 0 'kJ/kgTS)' 'pre-treatments' followed by anaerobic digestion provoked reproducible clostridia increases. 'Emerging' interest has recently focused on markers of oxidative stress and neuroinflammation in schizophrenic spectrum 'disorders,' at least in particular subgroups of patients. 'Our' findings establish that high purity lonsdaleite is readily formed under strain and hence does not require meteoritic impacts. 'Even' though an increase in mtDNA4977 deletion was found in all study 'groups,' the difference was not statistically significant ( 'p=0'. 'Sleep' spindles act as a powerful marker of individual differences in cognitive ability. 'Most' plants primarily procure 'N' as inorganic nitrate ( 'NO3(-)') or ammonium ( 'NH4(+)'), using 'membrane-localized' transport proteins in 'roots,' which are key targets for improving 'N' use. 'We' proposed a novel method of 'fern-mediated' biosynthesis of silver nanoparticles ( 'AgNP)' using 'Dicranopteris' 'linearis,' acting as a reducing and capping agent. 'This' work may thus help to determine experimental strategies with the capacity to enhance hydrogen storage. 'Structural' details provide new insights into 'sub-steps' during the catalysis of peroxide 'reduction,' enabling the transition from an 'FF' to a 'LU' conformation. 'The' 'Tamil' 'Nadu' model of public health is renowned for its success in providing quality health services at an affordable cost especially to the rural people. 'Diosmin' caused 'G2/M' cell cycle 'arrest,' elevation in 'p53,' p21 and p27 levels and 'stress-induced' premature senescence when used at lower concentrations ( 5 and 10 'μM)'. 'Taken' 'together,' diosmin that acts at low micromolar range against breast cancer cells may be considered as a promising candidate for anticancer therapy. 'Notably,' phyB induces 'HOS1' activity in inhibiting 'PIF4' function. 'Pre-clinical' models substantiate that the relationship is a genuinely causal one. 'New' small lakes formed in the deglaciated 'areas,' increasing the flooded area from1. 'Secondary' 'Fe' oxyhydroxides act as a 'long-term' sink for 'As' under present day hydrologic settings in waste rock dumps in the 'Elk' 'Valley'. 'Periprosthetic' osteolysis induced by wear particles can lead to aseptic 'loosening,' one main reason of arthroplasty failure. 'Metal' deposition on oxide surfaces usually results in 'adatoms,' 'clusters,' or islands of the deposited 'material,' where defects in the surface often act as nucleation centers. 'Particularly,' researchers and the public have shown increasing interest in the combination of probiotics with natural substances that promote health or that can act as substrates to promote bacterial growth. 'Tocopherols' as antioxidants have been studied both exogenously and endogenously. 'Slow' and deep inhalation of 'FP/FM-pMDI' is effective in many asthmatic patients who have prolonged 'small-airways' dysfunction. 'MACRA' has dramatic implications for all 'US' based healthcare providers. 'Neurointerventionalists' will predominantly participate in 'MIPS'. 'Adolescent' men reported more violent 'PTEs' ( e. 'Pearson\'s' correlation coefficients indicated a high 'correlation,' thus suggesting a directly proportional relationship between cell surface 'LRP/LR' levels and the adhesive and invasive potential of 'AsPC-1' and 'IMR-32' cells. 'Cardiovascular' 'diseases,' increased values of urea over 8.3 'mmol/l' and 'SAPS' score are independent predictive indicators for lethal outcome in severe influenza. 'Id3' then heterodimerizes with the basic 'helix-loop-helix' transcription factor 'E47' and releases the 'E47-mediated' repression of 'astrocyte-specific' gene expression. 'It' also affects cell metabolism by inhibiting 'mTOR,' 'GSK-3α/β,' and activating 'AMPK'. 'Neighborhood' walkability has been shown to be associated with walking behavior. 'Participants' reported past week 'WT' frequency. ',' 'aromatization,' benzylic 'oxidation)' led to a reduced activity or a complete loss of cytotoxicity. hospital industry has recently witnessed a number of policy changes aimed at aligning hospital payments to costs and these can be traced to significant concerns regarding selection of profitable patients and procedures by 'physician-owned' specialty hospitals. 'CuAlO2:Eu(3+)' nanofibers have been prepared via electrospinning for the ease of mitigating synthesis requirements and for future optoelectronics and emerging applications. armigera and possibly involved as carriers for carotenoids and visual pigments. 'Traditionally,' keloids have been considered as a result of aberrant wound 'healing,' involving excessive fibroblast participation that is characterized by hyalinized collagen bundles. 'Transgenic' 'cotton,' expressing a single 'Bt' 'toxin,' was first used in the 1990 s to control 'H'. 'The' aim of the present study is to determine the threshold concentration below which proven synergists cease to act as synergists towards the aquatic crustacean 'Daphnia' magna. 'This' study evaluates how 'CUR' influences the induction of apoptosis and oxidative stress in couples of adult 'S'. 'Ab' initio 'MP2/aug\'-cc-pVTZ' calculations have been carried out to investigate hydrogen 'bonding,' halogen 'bonding,' and pnicogen bonding involving tetrahedral 'P4' and the 'FH,' 'ClH,' and 'FCl' molecules. 'In' times of economic 'constraint,' organisations need to focus their efforts on targeted leadership initiatives. 'Previous' research undertaken in skill acquisition was used to provide support for the framework. 'Men' reporting both male and female sexual partners ( 'MSMW)' between 2002 and 2009 ( 'n = 111)' were classified as behaviorally bisexual. 'There' are also a number of calculated 'parameters,' derived from these measured 'analytes,' which could also be considered for harmonisation. 'Rab' guanosine triphosphatases ( 'GTPases)' control cellular trafficking pathways by regulating vesicle 'formation,' 'transport,' and tethering. 'Confocal' microscopy images indicate the 'NKCC1' increase was pronounced in the initial axonal segment of granule cells. 'We' examined 'top-down' and 'bottom-up' effects on food web fluxes using a field experiment that manipulated the presence of a 'consumer,' the 'Trinidadian' guppy 'Poecilia' 'reticulata,' and the production of basal resources by thinning the riparian forest canopy to increase incident light. 'Forces' carried by the medial meniscus and by 'cartilage-to-cartilage' contact on the lateral femoral condyle changed by & 'lt;5' 'N' as a result of 'ACL' sectioning. 'BA' concentration decreased rapidly in the proximal gut. 'Nonetheless,' how individual 'TFs' act in concert to regulate mRNA gene expression in a single cell remains poorly understood. 'EPR' spectroscopy suggests that the 'NN' ligands act as bidentate and bind through both nitrogen donor atoms in an 'axial-equatorial' mode. 'Practice' facilitation that provided 'EHR' and 'QI' coaching support showed important improvements in diabetes outcomes in practices that achieved meaningful use of their 'EHR' systems. crucigerum and suggest the presence of compounds that may act as 'TRPV1' antagonists. 'Endangered' 'Species' 'Act' due to 'climate-change-induced' habitat loss. tumana occurrence increased with cold stream temperatures and close proximity to glaciers and permanent snowfields. 'Climate' 'warming-induced' glacier and snow loss clearly imperils the persistence of 'L'. 'Twenty-two' per cent reported calling 20 times or more in the past month ( frequent 'users),' 51 '%' reported calling between 2 and 19 times ( episodic 'users)' and 25 '%' reported calling once ( 'one-off' 'users)'. 'Fluctuating' asymmetry increased with mercury concentrations in whole blood and breast feathers of 'Forster\'s' terns ( 'Sterna' 'forsteri),' a species with elevated mercury concentrations. 'Simultaneously,' cadmium induced prominent 'BNIP-3' expression in the mitochondria and cytoplasmic 'AIF/Endo' 'G' translocation to the nucleus. coquimbensis fruits have higher probabilities of being 'harvested,' and ultimately of its seeds being hoarded and dispersed by 'scatter-hoarding' rodents. 'Researchers' are encouraged to include women in studies that involve asking about abuse experiences. 'We' show that the global 'rheology,' as well as the amplitude and correlation time of the 'fluctuations,' are consistent with a 'mean-field,' 'Landau-like' 'description,' where the strain rate and the stress act as conjugated variables. 'Nest' sanitation has been posited as a 'pre-adaptation' for egg ejection by hosts of avian brood parasites. 'Humans' act as an intermediate host for 'Toxocara' canis and 'Toxocara' cati. 'Current' cooking method requires the internal temperature of beef patties to reach 71 ° 'C'. 'Every' close relationship has a 'history,' but how people manage their relational past varies and can have important implications in the present. 'Here,' we visualized key cell events of 'immunotherapy-elicited' immunoreactions in a 'multicolor-coded' tumor 'microenvironment,' and then established an optimal strategy of metronomic 'combined-immunotherapy' to enhance 'anti-tumor' efficacy. 'We' synthesize interdisciplinary literature from 'Ghana' to highlight the complexity of communicable disease care in 'SSA' from 'biomedical,' 'social,' and environmental 'perspectives,' and suggest a way forward. 'Housing' adaptations have been identified as 1 of the 10 most promising prevention services for older 'adults,' with bathing adaptations being the most requested. 'State' licensing boards have obligations to protect the public from impaired professionals and to protect the rights of professionals applying for licensure. 'Competently' functioning professionals who have or have had a mental health diagnosis or are being treated for a mental health condition should not be screened 'out,' according to the 'Americans' with 'Disabilities' 'Act' ( 'ADA)'. 'Low' input and high utilisation can strengthen 'bottom-up' pathways and enhance consumer biomass and abundance. 'CRK28-mediated' cell death required the common 'RLK' 'co-receptor' 'BAK1'. 'Headaches' and facial pain have been identified as the most prevalent form of pain among patients with glioblastoma 'multiforme,' the most common malignant primary brain tumour. 'Behaviourally' spontaneous confabulation denotes a distinct syndrome consisting of confabulations that patients act 'upon,' 'disorientation,' and amnesia. 'TLE1' negatively regulates inflammation and has potential roles in various 'diseases,' including cancer. 'Cicada' songs act as 'species-specific' premating barriers and have been used extensively to reveal hidden taxonomic diversity in morphologically similar species. 'Based' on 'acoustic,' 'morphological,' 'molecular,' ecological and spatial data sampled throughout their broad 'European' 'distribution,' we find that 'Cicadetta' brevipennis s. 'The' fifth lineage requires additional investigation. brevipennis song groups exhibit 'characteristic,' clearly distinct basic song patterns that act as reproductive barriers. 'We' demonstrate that both receptors share certain signaling pathways ( 'RhoA,' 'Akt' and 'Erk),' but also use distinct signals to mediate 'CSPG' actions. 'Among' these 'signals,' dendritic 'NMDA' spikes are of interest in light of their correlation with synaptic 'LTP' induction. 'Epithelial' barrier function requires a contiguous layer of cells as well as the junctions that seal the paracellular space between epithelial cells. 'The' report card identifies gaps in both investments and research that need to be addressed before understanding the complete picture of active living in children and youth in 'India'. 'Kenya\'s' 2016 report card aimed to highlight the health and 'well-being' of 'Kenyan' children and youth using the best available evidence on the physical activity of 'Kenyan' children and youth. 'Countries' that lead in certain indicators often lag in others. 'The' main goal was to summarize and describe the current state of child and youth 'PA' to increase awareness and surveillance. 'Sources' included national 'surveys,' 'peer-reviewed' 'literature,' and gray literature such as government and nongovernment reports and online content. '\'' 'School' nurses alone cannot fill the gap in sex and relationships education but they can act as 'advocates,' providing 'one-to-one' advice for 'pupils\''. 'Ginsenoside' 'Rg1,' extracted from 'Radix' 'Ginseng,' exerts a['Formula:' see 'text]-secretase' inhibitor effect so as to decrease 'A[Formula:' see 'text]' aggregation. 'Those' admitted voluntarily reported higher levels of perceived coercion from internal 'sources,' and those admitted involuntarily perceived significantly higher coercion from legal sources. 'HCW' expressed satisfaction for the course approac. ',' noises that result in informational versus energetic masking. 'Polarization' dependent 'X-ray' absorption spectra reveal anisotropy in the electronic structure between the 'ab-plane' and 'c-axis'. 'Objective' 'The' basal ganglia are a group of structures that act as a cohesive functional unit. 'Prestructured' precursors that act as seeds and wet on the nuclei during nucleation always have a high degree of 'bcc-like' 'ordering,' despite different state points. 'Lead-free' relaxor ferroelectrics that feature a 'core-shell' microstructure provide an excellent electromechanical response. 'In' situ transmission electron microscopy studies show that the 'CNTs' not only play an essential role in accommodating the volume expansion of the 'Fe-S' 'NPs' but also provide a fast transport path for 'Li' ions. 'Anisotropic' scaffolds supported the enhanced migration of an invasive breast cancer cell line 'MDA-MB-231' with an altered spatial distribution of proliferative cells in contrast to invasive 'MDA-MB-468' and 'non-invasive' 'MCF-7 cells' lines. 'Abused' substances act on the 'brain\'s' reward 'system,' a neural circuit that produces pleasurable feelings in response to stimuli that promote 'survival,' thereby modifying future behavior to seek out similar stimuli. 'This' study was designed to assess the neuroprotective effect of naringin on ammonium chloride ( 'NH4Cl)' induced hyperammonemic rats. 'Mean' intake increased significantly more in the intervention than control group after controlling for gender and 'education,' 'F(1,' 85) = 4.09, p = 0.046. 'We' used a 'seven-day' 'PA' recall to collect screen time ( 'hours/week)' and 'leisure-time' sports participation ( 'yes/no)' since 2004. 'Employers' have access to many programs that could be beneficial to their 'employees\'' health. 'This' was accomplished by internal fixation of one side and central fixation of a 'full-open' distractor to act as compression device when reversely activated. 'Endogenous' neurosteroids and neuroactive steroids have potent and widespread actions on the brain via inhibitory 'GABAA' receptors. 'For' groups that can implement change 'rapidly,' 'efficiently,' and 'harmoniously,' there will be opportunities to achieve the 'Triple' 'Aim' goals of the 'Patient' 'Protection' and 'Affordable' 'Care' 'Act,' while maintaining a successful 'medical-financial' practice. 'Stephen' 'Napier' has argued against the soundness of what he calls the & 'quot;Canon-Law' 'argument"' against the moral permissibility of a couple employing a condom for the sake of one spouse avoiding the contraction of 'HIV' from the other spouse. 'Symptoms' associated with mania can include increased creativity and 'productivity;' 'however,' mania can also lead to immediate hospitalization or involuntary committal under the 'Mental' 'Health' 'Act'. 'RESUMO' 'O' tabagismo é o fator de risco mais prevenível e controlável em saúde 'e,' por 'isso,' precisa ter a máxima atenção e ser muito mais enfocado por todos os profissionais da saúde. 'Entretanto,' ainda resta um longo caminho a ser percorrido para que se possa considerar o tabagismo como uma doença controlada sob o ponto de vista da saúde pública. 'We' have analyzed 19 , 463 participating 'students\'' 'pre-' and 'post-tests' within the program to examine their learning growth and attitude changes towards science. 'Countries' in all six 'WHO' regions have adopted measles elimination goals. 'Viewed' objects have been shown to afford suitable 'actions,' even in the absence of any intention to act. 'AOX' acts as a means to relax the highly coupled and tensed electron transport process in mitochondria thus providing and maintaining the much needed metabolic homeostasis by directly reducing oxygen to water. 'However,' more 'mixed-methods' studies are needed to develop deeper insights into the observed unintended adverse 'outcomes,' including their root causes and remedies. 'An' 'Au' grating was fabricated on an 'n-type' silicon wafer to form a 'Schottky' barrier and act as an 'SPR' coupler. 'We' use an approach in which one lens controls the spot 'divergence,' and one to two decentered lenses act as prisms and steer the beam. 'Our' previous studies showed that 'Pluronic' 'P85' augments radiation cancer cell killing of ( '±)-gossypol' in vitro. 'Mitotic' exit requires the inactivation of 'cyclin-dependent' kinase ( 'Cdk)' activity and reversal of 'Cdk-mediated' phosphorylation events by protein phosphatases. 'Phenylethanol' ( 'PEtOH)' is a constituent of essential oils with a pleasant odor and can act as a local anesthetic. 'Calculated' 'MM/GBSA' binding energies for 'OHCs' in complex with the 'CRD' of 'Smoothened' correlate well with in vitro 'Hh' modulatory activity. 'Reactive' astrogliosis has been occurred after intracerebral hemorrhage ( 'ICH)'. 'Silver' nanoparticles have the talent to anchor to the bacterial cell wall and consequently infiltrate 'it,' so causing physical modifications in the cell membrane like the absorptivity of the cell membrane and death of the cell. 'H2O2' determined an increase in endogenous cytokines involved in the response to oxidative stress and 'GO' 'pathogenesis,' namely 'TNF-alpha,' 'IL1-beta' and 'IFN-gamma'. 'SeMCys' reduces 'HA' release in 'GO' fibroblasts in a manner that seems at least in part independent from 'H2O2-induced' oxidative stress. 'Bacterial' 'PHAs' act as an internal reserve for carbon and energy and also are a tremendous alternative for fossil 'fuel-based' polymers mainly due to their 'eco-friendliness'. 'Furthermore' we show 'that,' like other exported 'proteins,' trafficking of 'PfHsp70x' requires the vacuolar 'translocon,' 'PTEX'. 'Emulsion' droplets act as very numerous small reaction chambers in which different 'PCR' products from a single genomic 'DNA' molecule are condensed into short joint 'products,' to unite sequences in cis from widely separated genomic sites. 'CaBP4' and 'CaBP5' have been shown to be important for normal visual function. 974 'ASSH' members responded to the survey ( 33 '%' response 'rate)'. 'In' other 'cases,' it requires strategic thinking. 'However,' unlike their counterparts at glutamatergic 'synapses,' gephyrin and its binding partners lack canonical protein interaction 'motifs;' 'hence,' the molecular basis for gephyrin scaffolding has remained unclear. 'Among' 'plant-microbe' 'interactions,' symbiotic associations of arbuscular mycorrhizal fungi ( 'AMF)' and arbuscular 'mycorrhizal-like' fungus especially 'Piriformospora' indica with plants are well known to improve plant growth by alleviating the 'stress-impacts' and consequently enhance the plant fitness. 'Pontine' noradrenaline has been shown to increase upon trauma and associated 'β-adrenergic' receptor activation appears to consolidate memory formation of traumatic events. 'Plasma' constituents that act as surrogates of altered hepatic energy metabolism in response to food intake are likely candidates. 'Repressor' 'MYB3Rs' act outside the mitotic time window during cell cycle 'progression,' and are important for the shutdown of mitotic genes to impose quiescence in mature organs. 'Cu(2+)' can catalyze the oxidation of sulfhydryl groups in glutathione ( 'GSH)' which act as a stabilizer for 'CdS' 'QDs'. 'Face-work' 'Theory' provides a framework to understand these interaction processes in 'pharmacist-patient' communication. 'Linking' speech acts with face needs and threats may help to elucidate how 'pharmacist-patient' interactions achieve both task oriented and interpersonal goals. 'We' examined this relationship and found the followings. 'Eighty-six' percent reported that the weekly learning goals increased their awareness of their thoughts and actions. 'Ephemeral' rivers act as linear oases in drylands providing key resources to people and wildlife. 'Such' introgression has not been recorded previously in these two 'species,' and the imbalance in hybridization direction may have important implications for restocking programs. 'Shortening' the sputtering 'time,' increasing the 'sputtering-gas' pressure or decreasing the substrate bias voltage can help synthesize 'WSe2' films with more platelets embedded vertically in the matrix. 'Newer' medicines have also raised concerns in terms of efficacy and safety. 'The' present study aimed to investigate the effects of berberine ( 'BRB)' on spatial and learning 'memory,' 'anxiety,' acetylcholinesterase activity and cell death in an experimental model of intracerebroventricular streptozotocin ( 'ICV-STZ)' induced sporadic 'Alzheimer\'s-like' dementia. 'Specially,' 'YopJ' interacts with 'STING' to block its 'ER-to-Golgi' traffic and remove its 'K63-linked' ubiquitination chains. 'In' contrast to common trivalent boron 'compounds,' the 'boron-based' ligands in this study act as 'electron-donating' ligands. bronchiseptica mutant lacking 'ACT' produced more biofilm than the parental 'strain;' leading 'Irie' et al. 'AC' 'Domain' interacts with the 'C-terminal' segment of 'FHA' with '∼650' nM affinity. 'It' is concluded that night shifts increase mean hunger and anxiety scores. 'Alpha-theta' oscillations can be interpreted as the rhythmic gating signature in a speech executing 'subthalamic-prefrontal' network. 'These' results indicate that 'PPB' reduces the excitability of 'CA1' pyramidal neurons by modulating 'voltage-dependent' sodium channels. the 'oxysterome)' involved in a plethora of physiological processes. 'EBI2,' 'SMO,' 'CXCR2),' nuclear receptors ( 'LXR,' 'ROR,' 'ERα)' and through transporters or regulatory proteins. 'Fast' neurotransmitters act in conjunction with slower modulatory effectors that accumulate in restricted synaptic spaces found at giant synapses such as the calyceal endings in the auditory and vestibular systems. 'Here,' zeolite acted as a preserving reservoir of ammonium where both sorption and desorption took place when needed and this caused the 'Anammox-zeolite' system to act as a buffer system to generate a stable effluent. 'OT' and 'VP' act on the kidneys controlling the excretion of water and sodium to maintain homeostasis. 'Nanowire' networks act as 'self-healing' smart 'materials,' whose sheet resistance can be tuned via an externally applied voltage stimulus. 'MGRN1' ubiquitinates and regulates tumour susceptibility gene 101 ( 'TSG101),' a central component of the endosomal trafficking machinery. 'Statins' induce apoptosis of tumor cells by inhibiting the prenylation of small 'G-proteins'. 'Follicle' 'number,' increasing cycle length and evidence of hyperandrogenism were all independently associated with serum 'AMH' concentration ( 'P' & 'lt;' 0 '·01)'. 'Serum' 'AMH' has the capacity to act as a diagnostic test for 'PCOS'. strain 'AN3' has a noncatalytic glutamine residue ( 'Gln241)' at an equivalent 'position,' surrounded by hydrophilic residues ( 'Thr214' and 'His215)'. 'Preliminary' testing has shown an efficiency of well above 80 '%' using two cells and three sets of discharge electrodes. 'Gold' nanoparticles ( 'GNP)' act as a radiosensitizer in radiation therapy. 'Finally,' we used luciferase reporter assays to show that several of the 'PGs' in the lipidome of activated 'HLFs' independently activate 'PPARγ' 'and/or' inhibit 'NFκB'. 'Cannabinoids' apparently act on inflammation through mechanisms different from those of agents such as nonsteroidal 'anti-inflammatory' drugs ( 'NSAIDs)'. 'Rural' and 'low-income' parents reported significantly higher barriers. 'Seventeen' schools provided data from students aged 11 to 13 years ( n = 1226), parents ( n = 192), and teachers ( n = 14) via direct observation and questionnaires. 'Participants' identify career progression and professional development as significant as well as the status and independence of the role and enhanced job security. 'Propofol' and sevoflurane act differently on cerebral blood vessels. 'Transmuscular' migration of the encircling band through rectus muscles and straddling of the cornea may act as a trigger for glaucoma. parasiticus and to act as an 'anti-mycotoxin'. 'There' are many and often intricate causes for aseptic loosening. 'Malaria-endemic' countries have implemented community health worker ( 'CHW)' programs to provide malaria diagnosis and treatment to populations living beyond the reach of health systems. 'The' 'C═O' group could act as act as electron 'acceptors,' facilitating the electron transfer for 'Hg(0)' oxidation. 'However,' migratory 'SMCs' did not uptake acetylated 'low-density' lipoprotein or express the classic macrophage marker 'CD68'. 'Previous' research has suggested that cAMP inhibits myometrial contractions via protein kinase 'A' ( 'PKA)' 'activation,' but this has yet to be demonstrated with 'PKA-specific' agonists. 'Our' findings suggest that 'PKA' is not the sole mediator of 'cAMP-induced' myometrial relaxation and that prolonged prophylactic elevation of cAMP alone is unlikely to prevent preterm labour ( 'PTL)'. 'Surprisingly' little attention has been given to aspects of tubular transport function in 'AKI' and the relevance for kidney recovery. 'ACA' legislation increased drug rebates for manufacturers participating in the 'Medicaid' 'Drug' 'Rebate' 'Program'. 'Hippocampal' granule cells generated in the weeks before and after an epileptogenic brain injury can integrate abnormally into the dentate 'gyrus,' potentially mediating temporal lobe epileptogenesis. 'The' present study also demonstrates that granule cell 'ablation,' while reducing seizure 'frequency,' paradoxically increases seizure duration. 'Platelets' compartmentalize glycosyltransferases and release them upon activation. 'Ethics' approvals have been obtained through the 'Children\'s' 'Health' 'Queensland' 'Hospital' and 'Health' 'Service' 'Human' 'Research' 'Ethics' 'Committee' ( 'HREC/15/QRCH/115)' and 'The' 'University' of 'Queensland' ( 2015001743). 'Via' various binding partners of these 'domains,' 'Shank3' is able to bind and interact with a wide range of proteins including modulators of small 'GTPases' such as 'RICH2,' a 'RhoGAP' 'protein,' and 'βPIX,' a 'RhoGEF' protein for 'Rac1' and 'Cdc42,' actin binding proteins and actin modulators. 'Supramolecular' brush copolymers have attracted continuing interest due to their unusual 'architectures,' fascinating 'properties,' and potential applications in many fields involving smart 'stimuli-responsive' drug delivery systems. 'The' literature has conflicting views on the relationship between facial fractures and head injuries with some authors opining that the facial skeleton cushions the brain while some other authors claim that the facial fractures act as indicators for head injuries. 'Hyperosmotic' shock caused arrest of 'growth,' loss of 'turgor,' and hypercondensation of chromosomes. 'To' better understand the genus 'Lepilemur,' we analyzed 35 complete mitochondrial genomes representing all recognized 26 sportive lemur taxa and estimated divergence dates. 'We' used 'three-dimensional' 'cryo-electron' microscopy combined with complementary biophysical techniques to determine the structures of 'RnQV1' virion strains 'W1075' and 'W1118'. 'A' single crystal 'X-ray' diffraction study of the representative complex['(' 'Cu(L)(PPh3)2]CIO4' ( 2) reveals a distorted tetrahedral geometry around 'Cu(I)'. 'Noncoplanar' 'PCB40' and coplanar 'PCB77' exhibited 'concentration-' and 'time-dependent' biphasic 'dose-response' effects on 'HELF' cell proliferation. 'In' some 'instances,' the 'patients\'' refusal may jeopardize their health or life but also compromise the 'clinician\'s' moral responsibility to promote the 'patient\'s' best interests. 'New' 'phage-based' technologies have led to the construction of different peptide 'libraries,' and recognition abilities provided by novel targeting ligands. 'The' morphology of the treated skin samples was thoroughly investigated by transmission electron microscopy and stimulated 'Raman' spectromicroscopy. 'Heteropentamer' nAChRs have diverse characteristics and can form canonical and noncanonical subunit interfaces. 'Four' histidine residues ( 'His37)' in the center of the channel act as a pH sensor and proton selectivity filter. 'Dental' caries has been traditionally described as a multifactorial disease that involves the interaction of various factors like 'host,' 'agent,' substrate and time. 'It' is primarily a rodent parasite and humans ( usually 'children)' can act as accidental hosts. 'Here,' we show that the 'β-arrestin1/STAM1' 'complex,' initially identified to govern lysosomal trafficking of 'CXCR4,' also mediates 'CXCR4-dependent' chemotaxis. 'Left' ventricular pressure overload induced by transverse aortic constriction ( 'TAC)' in mice resulted in left ventricular 'dysfunction,' fibrosis and increased biglycan expression. 'Another' hour later he appeared in the emergency room with a grade 3 systemic anaphylaxis. 'Why' do people act 'altruistically?' 'One' theory is that empathy is a driver of morality. 'Food' addiction has been proposed as an extreme form of 'compulsive-overeating' and has been associated with genetic markers of heightened reward responsiveness. 'Strong' social capital is increasingly recognized as an organizational advantage. 'High-frequency' temperature fluctuations caused no deviations from typical coevolutionary arms race dynamics. 'Carotenoids' and retinoids have several similar biological activities such as antioxidant 'properties,' the inhibition of malignant tumour growth and the induction of apoptosis. 'In' 'addition,' we demonstrate that engineering the entrance tunnel is an efficient strategy to regulate enzyme catalytic capabilities. 'Our' work now enables the production of 'Fab' and 'F(ab\')2' for therapeutic and diagnostic immune assays that have minimal reactivity toward 'pre-existing' 'AHA'. 'Fertile-sterile' dimorphy has evolved multiple times in ferns in spite of the apparent physiological costs associated with a reduction in photosynthetically active tissues. ( 'PsycINFO' 'Database' 'Record' 'Rhipicephalus' ( 'Boophilus)' microplus ticks are obligatory hematophagous ectoparasites of cattle and act as vectors for 'disease-causing' microorganisms. 'Recognizing' that organismality can be context 'dependent,' we advocate elucidating the ecological contexts under which entities do or do not act as organisms. 'Primarily,' we find that 'Brazilian' 'H'. ',' 'irisin,' 'IL-6,' 'LIF,' 'IGF-I)' 'which,' 'instead,' act as 'inflammatory/pro-resorptive' mediators when chronically 'elevated;' on the other 'hand,' the reduction in the circulating levels of adipokines ( i. 'For' these reason 'these participants' found the placement a beneficial and worthwhile experience. 'Renal' cells also express ectonucleotidases that rapidly hydrolyze extracellular nucleotides. 'This' concept will help in the search of new drugs that act as 'senescence-inductors'. 'R:FR' and blue lights increased emissions under low 'light,' but the results varied with 'species,' providing evidence that both light quantity and quality regulate 'CH4' emissions. 'Vesicles' are primarily fabricated by['M-n-M](2+)@2[DBS](-),' and then successively fused into vesicle 'clusters,' 'nanotubes,' and planar 'bilayers,' whose bilayer curvatures are gradually 'decreased,' with increasing spacer length. 'This' indicates a promising possibility for measurement of these chlorinated pigments as indicators of specific inflammatory states wherein betacyanins and decarboxylated betacyanins act as hypochlorite scavengers. 'Mechanistic' hypotheses have implied the recruitment of noradrenergic descending pathways as well as the peripheral recruitment of noradrenaline from sympathetic fibers sprouting into dorsal root 'ganglia;' and importance of both α2 and β2 adrenoceptors have been reported. 'Novel' 'protein interactions' suggest a highly complicated process rather than the simple removal of unnecessary genes. 'Cardiomyopathy' and associated heart failure continues to be one of the most severe complications that threaten a large population. 'Endomorphins' are natural amidated opioid tetrapeptides with the following 'structure:' 'Tyr-Pro-Trp-Phe-NH2' ( 'endomorphin-1),' and 'Tyr-Pro-Phe-Phe-NH2' ( 'endomorphin-2)'. 'Our' integrated metabolomics approach also provides a 'tractable,' powerful tool for understanding the science behind 'TCM' formulations. 'Twenty-eight' male inmates participated in qualitative interviews across three correctional centres in 'New' 'South' 'Wales,' 'Australia'. melazonatus and 'Iguanodectes' 'geisleri)' found under different 'co-occurrence' circumstances in 'Amazonian' upland streams. 'With' over half of the suitable habitat for three of the six species was located in coastal zones during 'drought,' our study highlights the need to identify and conserve coastal drought refuges. 'Hippocampal' neurogenesis has been proposed to participate in a myriad of behavioral 'responses,' both in basal states and in the context of neuropsychiatric disorders. 'Troglitazone' acted as a potent peroxyl radical 'scavenger,' whereas probucol and edaravone showed only moderate reactivity and 'carvedilol,' 'pentoxifylline,' and ebselen did not act as radical scavenger. 'Probucol' and edaravone suppressed plasma oxidation mediated by peroxynitrite and hypochlorite. 'MIG1' downregulation leads to malformed 'arbuscules,' a phenotype rescued by 'Δ18DELLA1,' suggesting that 'MIG1' intersects with the 'GA' signaling to control cell morphogenesis through 'DELLA1'. 'This' indicates that 'HBx-mediated' 'TLN1' degradation is essential and sufficient to stimulate 'HBV' replication. 'While' variability in active play definitions did 'exist,' common themes 'included:' increased energy 'exerted,' rough and 'tumble,' gross motor 'movement,' 'unstructured,' freely 'chosen,' and fun. 'Public' parks hold promise for promoting 'population-level' 'PA,' but studies show a significant portion of park use is sedentary. 'As' such the 'Delta' acts as a regional 'hydro-refugium'. 'In' 'locusts,' two lobula giant movement detector neurons ( 'LGMDs)' act as looming object detectors. 'Between' 2006 and 2015 , the 'Act' on the 'State' 'Emergency' 'Medical' 'System' was the key act governing the 'organization,' financing and provision of emergency care in 'Poland'. 'Overall,' results support enhanced 'use-specific' proprioception. 'PCC' 6803 , transcription of petE and petJ is activated and 'repressed,' 'respectively,' by 'Cu'. 'Correlates' differed for boys and 'girls,' suggesting that interventions should consider both the target population as well as the activity behavior. 'Transit-related' walking provides a potential opportunity to promote general walking 'behavior,' yet few studies have examined this issue. 'Liver' resection has been associated with high morbidity and 'mortality,' and the most serious complication is liver failure. 'Sociodemographic' 'variables,' 'pathology,' and the surgical act were 'analyzed,' together with morbidity and mortality and their associated factors. 'No' significant associations were found amongst girls. 'Village' midwives have been popular in 'Brunei' since the 1900 's,' with their major role being to assist women with childbirth. bolteae contained lactose operons involving 'PTS' system and complex 'regulation,' which contribute to phenotypic differentiation from 'C'. 'Seven' myths associated with machine learning and big data are then 'presented,' with the aim of managing expectation of machine learning amongst clinical chemists. 'parks,' 'lawns,' golf 'courses)' 'increased,' suggesting that natural ecosystem land cover types supported birds with a lower prevalence of infection. 'Absolute' peak power decreased between 'C1-C2' ( 'p<'. 'The' main aim of the study is to identify important residues of the 'Klotho' that help in designing peptides which can act as 'Wnt' antagonists. 'Glycolipid' 'GL1' has been identified as 'β-D-Glcp-(1→6)-α-D-Galp-(1→2)-α-D-Glcp-diglyceride' and 'GL2' as 'α-D-Galp-(1→2)-α-D-Glcp-diglyceride'. 'Here,' we investigated the use of 'layer-by-layer' ( 'LbL)' nanocoating of the surface of live 'BCG' with several layers of 'polyinosinic-polycytidylic' acid ( 'poly(I:C)),' a strong inducer of 'cell-mediated' 'immunity,' and the biodegradable polysaccharide chitosan to enhance 'BCG' immunogenicity. 'The' approach is demonstrated for 'Staphylococcus' aureus sortase 'A' ( 'SrtA),' which is an established drug target and biotechnological reagent. 'Some' of these interventions are concerned with helping individuals make more informed 'decisions;' 'others,' 'however,' are designed to compel people to act as the intervener sees fit. 'Subsequent' studies in mammalian cell systems implicated eIF2A in 'non-canonical' ( 'non-AUG-dependent)' translation initiation events involving near cognate 'UUG' and 'CUG' codons. 'Ancestral' morphological reconstruction suggests lake colonization by a generalist oreochromine phenotype that diverged in 'Lake' 'Natron' to varied herbivorous morphologies akin to specialist herbivores in 'Lakes' 'Tanganyika' and 'Malawi'. 'Structure-activity' relationships suggest two pathways sensing these compounds in the maize pathogen 'Cochliobolus' 'heterostrophus,' one triggering a stress 'response,' and one inducing enzymes for their degradation. 'Thiosalicylamide' analogs have previously been shown to act in cells as acyltransfer catalysts that are capable of transferring cellular 'acetate,' presumably from 'acetyl-CoA,' to 'HIV' 'NCp7'. 'Management' authorities seldom have the capacity to comprehensively address the full suite of anthropogenic 'stressors,' particularly in the coastal zone where numerous threats can act simultaneously to impact reefs and other ecosystems. 'Hence' selective targeting of activated p65 is an attractive therapeutic strategy for 'AD'. 'Fucoidans' are marine sulfated 'polysaccharides,' which act as glycosaminoglycans mimetics. 'Temporal' variability has been observed for all these 'organisms,' mostly triggered by global changes in 'temperature,' relative 'humidity,' et cetera. 'Adult' life events partially mediated the association of parental divorce ( 'OR' 6.34, 95 '%' 'CI'-7.16 to 36.75) and physical ( 'OR' 9.59, 95 '%' 'CI' 4.97-27.88) and sexual abuse ( 'OR' 6.59, 95 '%' 'CI' 2.4-38.36) with suicidal ideation at 45 years. 'DM' parameters controls ( 'glycemia,' arterial 'tension,' and 'lipids)' are the gold standard for preventing 'DR' and 'DME'. 'We' showed that both 'ATL' cells ( 'C81' and 'HuT-102)' and 'patient-derived' cells released 'Tax-containing' exosomes. 'Apart' from its cytokine 'activities,' 'MIF' is known to act as a 'd-dopachrome' tautomerase. 'Southern' blot hybridisation established that most of them lacked the 'Rht-B1' 'gene,' but retained the homoeologues 'Rht-A1' and 'Rht-D1'. 'From' the 'MJ-treated' finger millet 'seedlings,' the 'EcJAZ' interacting proteins were purified by affinity chromatography with the 'EcJAZ-matrix'. 'The' selected antagonists could be applied before harvesting to control apple infection by 'PAT-producing' fungi and also during processing to act as 'PAT' detoxifiers. 'Experiments' assessing seed set after single flower visits were performed to determine whether thieving 'short-billed' sunbirds can act as substitute pollinators. 'Existing' 'APMs' have yet to be determined as eligible. 'Multiple' agencies publish fatality summaries for wildland fire 'fighters;' 'however,' the reported number and types vary. 'Valproic' acid ( 'VPA),' a class 'I' and 'IIa' 'HDAC' inhibitor administration significantly decreased 'corticoid-induced' hypertension. 'Aqueous' miscible organic layered double hydroxides ( 'AMO-LDHs)' can act as organophilic inorganic flame retardant nanofillers for unmodified 'non-polar' polymers. 'Additionally,' chromium ( 'VI)' can act as an irritant. 'Diabetic' neuropathy has a profound impact in the quality of life of patients who frequently complain of pain. 'Thus,' we postulate that germlings from the soil spore bank act as paternal partners. 'Electrochemical' signal has been greatly enhanced for cell detection by introducing branched polymer scaffold that are carrying large quantities of 'Fc' moieties. 'Vinca' alkaloids have been approved as anticancer drugs for more than 50 & 'nbsp;years'. 'Stimulation' of these receptors may cause sensorimotor gating disturbances.
:- dynamic relacion/1. relacion([sujeto(['Phenobarbital', '(', 'PB)']), verbo([increases]), complemento([hepatic, 'drug/steroid-metabolic', capability, by, coordinately, activating, transcription, of, the, genes, encoding, various, metabolizing, enzymes])]). relacion([sujeto(['The']), verbo([nuclear]), complemento([receptor, 'CAR', was, first, implicated, as, a, transcription, factor, that, activates, the, cytochrome, 'P450', 'Cyp2b10', gene])]). relacion([sujeto(['In', response, to, 'PB,', 'CAR', forms, a, heterodimer, with, the, retinoid, 'X', receptor, '(', 'RXR),']), verbo([binds]), complemento([to, a, 'PB', response, element, '(', typified, by, 'DR-4', 'motif),', and, activates, transcription, of, the, gene])]). relacion([sujeto(['In', the, 'CAR-null', 'mouse,', 'PB', does, not, only]), verbo([induce]), complemento([the, 'Cyp2b10', 'gene,', but, also, induces, genes, encoding, various, metabolizing, enzymes])]). relacion([sujeto(['Thus,', 'CAR', is, a, general]), verbo([nuclear]), complemento([receptor, that, is, essential, for, 'PB', induction, of, 'drug/steroid', metabolizing, enzymes])]). relacion([sujeto(['PB', also]), verbo([induces]), complemento([amino, levulinate, synthase, 1, '(', 'ALAS-1),', the, 'rate-limiting', enzyme, in, heme, 'biosynthesis,', to, increase, heme, supply])]). relacion([sujeto(['However,', 'PB', induction, of, the, synthase, occurs, in, 'CAR-null', 'mice,']), verbo([suggesting]), complemento([that, 'CAR', does, not, coordinate, the, heme, synthesis, for, the, induction, of, 'drug/steroid', metabolism])]). relacion([sujeto(['The', apical, 'sodium-dependent', bile, salt, transporter, '(', 'ASBT/SLC10A2),', also, called, the, ileal, bile, acid, 'transporter,']), verbo([mediates]), complemento([the, intestinal, absorption, of, bile, salts])]). relacion([sujeto(['The', minimal, construct, that]), verbo([confers]), complemento([full, promoter, activity, contains, three, functional, hepatocyte, nuclear, factor, 1, alpha, '(', 'HNF1alpha)', recognition, 'sites,', explaining, the, dependence, of, 'ASBT', gene, expression, upon, 'HNF1alpha'])]). relacion([sujeto(['A']), verbo([nuclear]), complemento([receptor, binding, site, arranged, as, a, direct, hexanucleotide, repeat, '(', 'DR1', 'motif)', is, localized, approximately, 1.6, kb, upstream, of, the, transcription, initiation, site])]). relacion([sujeto(['The', 'DR1', element, was, shown, to]), verbo([bind]), complemento([the, 'PPARalpha/9-cis-retinoic', acid, receptor, 'heterodimer,', and, targeted, mutagenesis, of, the, 'DR1', motif, abolished, 'PPARalpha', responsiveness])]). relacion([sujeto(['Ciprofibrate', treatment, of, 'SK-ChA', cholangiocytes]), verbo([increased]), complemento(['ASBT', mRNA, 'levels,', suggesting, a, physiologic, role, for, 'PPARalpha-mediated', 'ASBT', gene, regulation])]). relacion([sujeto(['The', potency, and, hierarchy, of, bile, acids, as, ligands, for, the, 'farnesyl/bile', acid, receptor, '(', 'FXR/BAR)', paralleled, their, ability, to]), verbo([induce]), complemento(['BSEP', in, human, hepatocyte, cultures])]). relacion([sujeto(['FXR:RXR', heterodimers]), verbo([bound]), complemento([to, 'IR1', elements, and, enhanced, bile, acid, transcriptional, activation, of, the, mouse, and, human, 'BSEP/SPGP', promoters])]). relacion([sujeto(['In', 'FXR/BAR', nullizygous, 'mice,', which]), verbo([have]), complemento([dramatically, reduced, 'BSEP/SPGP', 'levels,', hepatic, 'CYP3A11', and, 'CYP2B10', were, strongly, but, unexpectedly, induced])]). relacion([sujeto(['Moreover,', the, hepatoprotective, bile, acid, ursodeoxycholic, 'acid,', which, reverses, hydrophobic, bile, acid, 'hepatotoxicity,']), verbo([activates]), complemento(['PXR', and, efficaciously, induces, 'CYP3A4', '(', a, 'bile-metabolizing', 'enzyme)', in, primary, human, hepatocytes, thus, providing, one, mechanism, for, its, hepatoprotection])]). relacion([sujeto(['Because', serum, and, urinary, bile, acids]), verbo([increased]), complemento([in, 'FXR/BAR', -, /, -, 'mice,', we, evaluated, hepatic, transporters, for, compensatory, changes, that, might, circumvent, the, profound, decrease, in, 'BSEP/SPGP'])]). relacion([sujeto(['We']), verbo([found]), complemento([weak, 'MRP3', 'up-regulation'])]). relacion([sujeto(['In', 'contrast,', 'MRP4', was, substantially]), verbo([increased]), complemento([in, the, 'FXR/BAR', nullizygous, mice, and, was, further, elevated, by, cholic, acid])]). relacion([sujeto(['Thus,']), verbo([enhanced]), complemento([hepatocellular, concentrations, of, bile, 'acids,', due, to, the, 'down-regulation', of, 'BSEP/SPGP-mediated', efflux, in, 'FXR', nullizygous, 'mice,', result, in, an, alternate, but, apparent, compensatory, 'up-regulation', of, 'CYP3A,', 'CYP2B,', and, some, 'ABC', transporters, that, is, consistent, with, activation, of, 'PXR/SXR', by, bile, acids])]). relacion([sujeto(['Major', transport, proteins]), verbo([involved]), complemento([in, the, enterohepatic, circulation, of, bile, salts, include, the, hepatocellular, bile, salt, export, pump, '(', 'BSEP,', 'ABCB11),', the, apical, 'sodium-dependent', bile, salt, transporter, '(', 'ASBT,', 'SLC10A2)', in, cholangiocytes, and, 'enterocytes,', the, 'sodium-dependent', hepatocyte, bile, salt, uptake, system, 'NTCP', '(', 'SLC10A1),', the, organic, anion, transporting, polypeptides, 'OATP-C', '(', 'SLC21A6),', 'OATP8', '(', 'SLC21A8)', and, 'OATP-A', '(', 'SLC21A3),', and, the, multidrug, resistance, protein, 'MRP3', '(', 'ABCC3)'])]). relacion([sujeto(['A', key, regulator, of, hepatocellular, bile, salt, homeostasis, is, the, bile, acid, 'receptor/farnesoid', 'X', receptor, 'FXR,', which]), verbo([activates]), complemento([transcription, of, the, 'BSEP', and, 'OATP8', genes, and, of, the, small, heterodimer, partner, 1, '(', 'SHP)'])]). relacion([sujeto(['SHP', is, a, transcriptional, repressor, that]), verbo([mediates]), complemento([bile, 'acid-induced', repression, of, the, bile, salt, uptake, systems, rat, 'Ntcp', and, human, 'OATP-C'])]). relacion([sujeto(['A']), verbo([nuclear]), complemento([receptor, that, activates, rodent, 'Oatp2', '(', 'Slc21a5)', and, human, 'MRP2', '(', 'ABCC2)', is, the, pregnane, 'X', 'receptor/steroid', 'X', receptor, 'PXR/SXR'])]). relacion([sujeto(['Intracellular', trafficking, and, membrane, insertion, of, bile, salt, transporters, is]), verbo([regulated]), complemento([by, 'lipid,', 'protein,', and, extracellular, 'signal-related', kinases, in, response, to, physiologic, stimuli, such, as, cyclic, adenosine, monophosphate, or, taurocholate])]). relacion([sujeto(['Finally,', dysfunction, of, individual, bile, salt, transporters, such, as, 'BSEP,', on, account, of, genetic, 'mutations,', steric, 'inhibition,', suppression, of, gene, 'expression,', or, disturbed, 'signaling,', is, an, important]), verbo([cause]), complemento([of, cholestatic, liver, disease])]). relacion([sujeto(['The', induction, of, 'CYP2B', gene, expression, by, phenobarbital, '(', 'PB)', is]), verbo([mediated]), complemento([by, the, translocation, of, the, constitutive, androstane, receptor, '(', 'CAR)', from, the, cytoplasm, to, the, nucleus])]). relacion([sujeto(['The', 'CAR/RXR', heterodimer]), verbo([binds]), complemento([to, two, 'DR-4', sites, in, a, complex, phenobarbital, responsive, unit, '(', 'PBRU)', in, the, 'CYP2B', gene])]). relacion([sujeto(['The', short, heterodimer, partner, '(', 'SHP),', an, orphan]), verbo([nuclear]), complemento([receptor, that, lacks, a, conventional, 'DNA', binding, 'domain,', was, initially, identified, by, its, interaction, with, 'CAR'])]). relacion([sujeto(['We']), verbo([have]), complemento([examined, the, role, of, 'SHP', in, 'CAR-mediated', transactivation, of, the, 'CYP2B', gene])]). relacion([sujeto(['Coexpression', of, 'SHP']), verbo([inhibited]), complemento([the, transactivation, of, the, 'CYP2B', gene, by, 'CAR', in, cultured, hepatoma, cells, and, the, p160, coactivator, 'GRIP1', reversed, the, inhibition])]). relacion([sujeto(['SHP', did, not, block, the]), verbo([binding]), complemento([of, either, 'CAR/RXR', to, the, 'PBRU', or, binding, of, 'GRIP1', to, the, 'CAR/RXR', complex, in, gel, mobility, shift, 'assays,', but, slightly, increased, 'CAR/RXR', binding, and, slightly, altered, the, mobility, of, the, 'CAR/RXR/GRIP1', 'complex,', suggesting, an, interaction, of, 'SHP', with, these, complexes])]). relacion([sujeto(['Recombinant', corepressors, 'mSin3A,', 'SMRT,', and, 'HDAC1,', but, not, 'NCoR1,']), verbo([interacted]), complemento([with, 'GST-SHP', but, each, of, these, corepressors, in, liver, nuclear, extracts, bound, to, 'GST-SHP'])]). relacion([sujeto(['SMRT', and, 'NCoR1']), verbo([inhibited]), complemento(['CAR-mediated', activation, independent, of, 'SHP,', but, mSin3A, and, 'HDAC1', had, little, effect, 'alone,', and, were, additive, with, 'SHP'])]). relacion([sujeto(['These', studies, demonstrate, that, 'SHP', does, not]), verbo([inhibit]), complemento(['CAR-mediated', 'trans-activation', by, interfering, with, 'DNA', binding, or, by, competition, with, 'GRIP1'])]). relacion([sujeto(['Instead,', 'SHP', may, either]), verbo([inhibit]), complemento([recruitment, of, other, coactivators, by, 'GRIP1', or, actively, recruit, corepressors, directly, to, the, 'CAR/RXR/PBRU', complex])]). relacion([sujeto(['One', of, these, regulatory, elements, overlapped, a, sequence, that, is, highly]), verbo([conserved]), complemento([in, most, members, of, the, 'CYP2', family])]). relacion([sujeto(['This', 'element,', which, consists, of, a, degenerate, 'AGGTCA', direct, repeat, spaced, by, 1, base, pair, '(', 'DR1)', and, is, known, to, be, a]), verbo([target]), complemento([for, members, of, the, steroid, receptor, 'superfamily,', was, found, to, bind, in, vitro, translated, hepatocyte, nuclear, factor, 4, '(', 'HNF4)', in, gel, retardation, analysis])]). relacion([sujeto(['Using', 'HepG2']), verbo([nuclear]), complemento(['extracts,', three, 'protein-DNA', complexes, were, formed, on, the, 'DR1', 'element,', one, of, which, was, confirmed, to, be, dependent, on, the, binding, of, 'HNF4'])]). relacion([sujeto(['Experiments', in, 'COS-7', cells, showed, that, 'HNF4', could]), verbo([activate]), complemento([the, 'CYP2D6', promoter, 30, -, fold])]). relacion([sujeto(['Surprisingly,', mutation, of, the, 'DR1', element, produced, a, relatively, minor, 23, '%']), verbo([decrease]), complemento([in, activity, in, 'HepG2', cells])]). relacion([sujeto(['Additionally,', 'COUP-TFI', was, shown, to]), verbo([inhibit]), complemento(['HNF4', stimulation, of, the, 'CYP2D6', promoter, in, 'COS-7', 'cells,', suggesting, that, 'COUP-TFI', could, attenuate, the, effect, of, 'HNF4', in, 'HepG2', cells])]). relacion([sujeto(['However,', when, 'HNF4', levels, were]), verbo([increased]), complemento([in, 'HepG2', cells, by, 'co-transfection,', it, resulted, in, the, enhancement, of, 'CYP2D6', promoter, 'activity,', indicating, that, 'HNF4', could, overcome, the, repressive, effect, of, 'COUP-TFI'])]). relacion([sujeto(['Therefore,', the, contribution, of, the, 'DR1', element, in, controlling, the, transcription, of, the, 'CYP2D6', gene, depends, on, the, balance, between, positively, and, negatively]), verbo([acting]), complemento([transcription, factors])]). relacion([sujeto([1, ',', 25, 'Dihydroxyvitamin', 'D', '(', 1, ',', 25, '(', 'OH)(2)D)']), verbo([regulates]), complemento([the, differentiation, of, keratinocytes])]). relacion([sujeto([1, ',', 25, '(', 'OH)(2)D', raises, intracellular, free, calcium, '(', 'Cai)', as, a, necessary, early, step, toward]), verbo([stimulating]), complemento([differentiation])]). relacion([sujeto([1, ',', 25, '(', 'OH)(2)D']), verbo([induces]), complemento([the, calcium, sensing, receptor, '(', 'CaR)', in, keratinocytes, and, enhances, the, calcium, response, of, these, cells])]). relacion([sujeto(['Activation', of, the, 'CaR', by, calcium]), verbo([increases]), complemento([intracellular, free, calcium, by, a, mechanism, involving, phospholipase, 'C', '(', 'PLC)', cleavage, of, phosphatidylinositolbisphosphate, into, inositoltrisphosphate, '(', 'IP(3))', and, diacylglycerol, '(', 'DG)'])]). relacion([sujeto([1, ',', 25, '(', 'OH)(2)D']), verbo([induces]), complemento([the, family, of, 'PLCs'])]). relacion([sujeto(['PLC-gamma1']), verbo([has]), complemento([a, 'DR6', 'VDRE', in, its, promoter, which, binds, and, is, activated, by, 'VDR/RAR', rather, than, 'VDR/RXR'])]). relacion([sujeto(['The', involucrin, 'gene,', which, encodes, a, critical, component, of, the, cornified, 'envelope,', contains, a, 'DR3', 'VDRE', in, its, promoter, that]), verbo([acts]), complemento([in, conjunction, with, a, nearby, 'AP-1', site])]). relacion([sujeto(['In', undifferentiated, 'keratinocytes,', the, 'VDR']), verbo([binds]), complemento([preferentially, to, the, 'DRIP', complex, of, coactivators])]). relacion([sujeto(['These', studies]), verbo([suggest]), complemento([that, at, least, part, of, the, sequential, activation, of, genes, required, during, keratinocyte, differentiation, is, regulated, by, the, change, '(', 'availability)', of, these, different, coactivator, complexes])]). relacion([sujeto(['The', gene, for, cholesterol, 7, 'alpha-hydroxylase', '(', 'CYP7A1)', contains, a, sequence, at, nt, -, 149, to, -, 118, that, was]), verbo([found]), complemento([to, play, a, large, role, in, determining, the, overall, transcriptional, activity, and, regulation, of, the, promoter])]). relacion([sujeto(['Hepatocyte']), verbo([nuclear]), complemento([factor, 4, '(', 'HNF4)', and, chicken, ovalbumin, upstream, promoter, transcription, factor, 'II', '(', 'COUP-TFII)', synergistically, activate, transcription, of, the, 'CYP7A1', promoter])]). relacion([sujeto(['Transactivation', of, 'CYP7A1', by, 'HNF4', in, the, human, hepatoma, cell, 'line,', 'HepG2,', was]), verbo([enhanced]), complemento([by, cotransfection, with, 'COUP-TFII', or, the, basal, transcription, element, binding, protein, '(', 'BTEB)'])]). relacion([sujeto(['HNF4', prepared, from, rat, liver]), verbo([nuclear]), complemento([extracts, bound, to, oligomers, homologous, to, the, nt, -, 146, to, -, 134, sequences, in, electrophoretic, mobility, shift, assays, '(', 'EMSA),', which, corresponded, to, a, conserved, region, containing, a, direct, repeat, of, hormone, response, elements, spaced, by, one, nucleotide, '(', 'DR1)'])]). relacion([sujeto(['The', sequences, surrounding, this, 'DR1', were]), verbo([found]), complemento([to, be, essential, for, the, 'HNF4', transactivation])]). relacion([sujeto(['In', 'vitro-translated', 'COUP-TFII', was]), verbo([found]), complemento([to, bind, the, adjacent, sequences, from, nt, -, 139, to, -, 128, '(', 'DR0),', but, 'COUP-TFII', interacted, with, this, region, at, a, much, lower, affinity, than, to, the, 'COUP-TFII-site', at, nt, -, 72, to, -, 57, '(', 'DR4)'])]). relacion([sujeto(['Mutations', at, nt, -, 139, to, -, 128, or, nt, -, 72, to, -, 57, reduced, the, 'COUP-TFII', and, 'HNF4', 'synergy;', 'however,', these, 'COUP-TFII-binding', sequences, were, not, absolutely]), verbo([required]), complemento([for, the, cooperative, effect, of, 'HNF4', and, 'COUP-TFII', on, transactivation])]). relacion([sujeto(['These', results, indicated, that, the, observed, transactivation, was, the, result, of, 'protein/protein', interactions, facilitated, by, the, juxtaposition, of, the]), verbo([binding]), complemento([elements])]). relacion([sujeto(['RAR-RXR', heterodimeric, complexes, '(', 'RARalphaDeltaAB-RXRalphaDeltaAB)']), verbo([bound]), complemento([to, cognate, 'DR5', 'DNA', response, elements, were, purified, to, apparent, structural, and, functional, homogeneity, using, a, novel, versatile, immobilized, metal, affinity, chromatography, '(', 'IMAC)', copurification, procedure])]). relacion([sujeto(['Using', heterodimers, purified, according, to, this, procedure, we, demonstrate, ligand]), verbo([binding]), complemento([of, 'RXR', in, the, context, of, the, 'RAR-RXR', 'heterodimer-DNA', complex])]). relacion([sujeto(['The', present, copurification, procedure, is, rapid, and]), verbo([has]), complemento([yielded, high, quality, 'heterodimer-DNA', complexes, suitable, for, both, structural, and, biochemical, studies])]). relacion([sujeto(['Hepatocyte']), verbo([nuclear]), complemento([factor, 1, alpha, '(', 'HNF1alpha)', and, 'HNF4alpha', are, 'liver-selective', transcription, factors, and, are, essential, for, hepatocyte, differentiation])]). relacion([sujeto(['This', study, demonstrates, that, 'HNF1alpha', as, well, as, 'HNF4alpha', genes, contain, a, direct, repeat, with, a, space, of, one, nucleotide, '(', 'DR1)-retinoic', acid, '(', 'RA)', response, element, that, can, be]), verbo([bound]), complemento([and, regulated, by, 'RA', and, retinoid, x, receptor, alpha, '(', 'RXRalpha)', complex])]). relacion([sujeto(['Transient', transfection, experiments, showed, that, 'RA']), verbo([increased]), complemento([the, promoter, activity, of, the, 'HNF1alpha', and, 'HNF4alpha', genes, in, 'Hep3B', cells])]). relacion([sujeto(['Overexpression', of, 'RXRalpha', further]), verbo([enhanced]), complemento([the, activities, of, both, genes])]). relacion([sujeto(['Two', putative, 'RXRalpha']), verbo([binding]), complemento([sites, on, the, 'HNF1alpha', '(', -, 295, to, -, 276, ')', and, 'HNF4alpha', '(', -, 418, to, -, 399, ')', genes, have, been, characterized])]). relacion([sujeto(['By', transient, 'transfection,', both, sites, positively]), verbo([responded]), complemento([to, 'RA,', and, overexpression, of, 'RXRalpha', in, 'Hep3B', cells, increased, the, regulatory, effect])]). relacion([sujeto(['Gel', mobility, shift, assay, demonstrated, that, these, two, 'DR-1', sites, could, be]), verbo([bound]), complemento([by, 'RXRalpha', specifically])]). relacion([sujeto(['These', data]), verbo([suggest]), complemento([that, the, differentiation, effect, of, 'RA', on, hepatocyte, may, be, due, to, direct, interaction, of, 'RXRalpha', with, the, 'RA-responsive', elements, on, the, 'HNF1alpha', and, 'HNF4alpha', genes])]). relacion([sujeto(['Peroxisome', 'proliferator-activator', receptors, '(', 'PPAR)', are]), verbo([involved]), complemento([in, cholesterol, homeostasis, through, the, regulation, of, bile, acids, 'synthesis,', 'composition,', and, reclamation])]). relacion([sujeto(['Indeed,', treatment, with, the, 'PPARalpha-PPARbeta/delta', agonist, bezafibrate]), verbo([led]), complemento([to, the, 'up-regulation', of, 'I-BABP', mRNA, levels, in, the, human, 'intestine-derived', 'Caco-2', cells])]). relacion([sujeto(['Electrophoretic', mobility, shift, assays, showed, that, the, 'PPAR/RXR', heterodimer, can, specifically]), verbo([bind]), complemento([to, this, 'PPRE-like', motif])]). relacion([sujeto(['The', regulation, of, the, 'I-BABP', promoter, by, 'PPAR', appears, 'species-specific,', as, the, mouse, 'I-BABP', 'promoter,', which, lacks, a]), verbo([conserved]), complemento(['PPRE,', was, not, responsive, to, exogenous, 'PPAR', expression, in, the, presence, of, bezafibrate])]). relacion([sujeto(['Our', findings, show, that, the, 'I-BABP', gene, may, be, a, novel]), verbo([target]), complemento([for, 'PPAR', in, humans, and, further, emphasize, the, role, for, 'PPAR', in, the, control, of, bile, acid, homeostasis])]). relacion([sujeto(['It']), verbo([has]), complemento([been, reported, previously, that, 'MDR3', expression, is, modulated, by, 'hormones,', cellular, 'stress,', and, xenobiotics])]). relacion([sujeto(['Here', we, show, that, the, 'MDR3', gene, is, 'trans-activated', by, the, farnesoid, 'X', receptor, '(', 'FXR)', via, a, direct]), verbo([binding]), complemento([of, 'FXR/retinoid', 'X', receptor, alpha, heterodimers, to, a, highly, conserved, inverted, repeat, element, '(', a, 'FXR', response, 'element)', at, the, distal, promoter, '(', -, 1970, to, -, 1958, ')'])]). relacion([sujeto(['In', 'FXR', 'trans-activation', 'assays,', both, the, endogenous, 'FXR', agonist, chenodeoxycholate, and, the, synthetic, agonist, 'GW4064']), verbo([activated]), complemento([the, 'MDR3', promoter])]). relacion([sujeto(['Consistent', with, these, 'data,', 'MDR3', mRNA, was, significantly]), verbo([induced]), complemento([by, both, chenodeoxycholate, and, 'GW4064', in, primary, human, hepatocytes, in, 'time-', and, 'dose-dependent', fashions])]). relacion([sujeto(['These', 'results,', together, with, the, previous]), verbo([report]), complemento([that, the, bile, salt, export, pump, is, a, direct, 'FXR', 'target,', suggest, that, 'FXR', coordinately, controls, secretion, of, bile, salts, and, phospholipids])]). relacion([sujeto(['BACKGROUND:', 'It']), verbo([has]), complemento([been, 'hypothesised,', mainly, from, studies, with, animal, models, of, liver, 'disease,', that, the, transport, of, substrates, for, metabolic, enzymes, and, their, subsequent, metabolism, and, elimination, in, hepatic, bile, or, blood, is, 'co-ordinated,', but, there, is, little, information, on, this, process, in, diseased, human, liver])]). relacion([sujeto(['METHODS:', 'In', this, study, we]), verbo([have]), complemento([measured, by, reverse, transcription, polymerase, chain, reaction, '(', 'RT-PCR)', major, genes, involved, in, drug, metabolism, from, 'UDP-glucuronosyltransferases', '(', 'UGT1A1,', 'UGT1A6,', 'UGT1A9,', and, 'UGT2B4)', and, cytochrome, 'P450', '(', 'CYP)', families, '(', 'CYP1A2,', 'CYP2C9,', 'CYP2C19,', 'CYP2D6,', 'CYP2E1,', and, 'CYP3A4),', transport, '(', 'OATP-C,', 'MRP2,', 'MRP3,', and, 'MDR1)', and, major, transcription, factors, '(', 'PXR,', 'CAR,', 'HNF1alpha,', 'HNF4alpha,', 'RXR,', and, 'AHR)', involved, in, their, regulation])]). relacion([sujeto(['An', unexpected]), verbo([finding]), complemento([was, that, this, was, substantially, greater, in, the, severely, diseased, liver])]). relacion([sujeto(['Cross-talk', between, transcription, factors, was, markedly]), verbo([increased]), complemento([in, tissue, from, patients, with, severe, liver, 'disease,', particularly, between, 'CAR,', 'HNF4alpha,', and, 'PXR'])]). relacion([sujeto(['CONCLUSION:', 'Our', results, support, the, hypothesis, of, 'co-ordinate', regulation, of, metabolic, enzymes, and, transporters, in, diseased, human, 'liver,', as, part, of, a, widespread, 'co-ordinated', process, under, the, control, of]), verbo([nuclear]), complemento([receptor, transcription, factors])]). relacion([sujeto(['Ninety', adult, human, livers, were, profiled, for, mRNA, expression, of, 'MRP2-4', as, well, as, aryl, hydrocarbon, receptor, '(', 'AhR),', constitutive, androstane, receptor, '(', 'CAR),', pregnane, 'X', receptor, '(', 'PXR),', peroxisome, 'proliferator-activated', receptor, alpha, '(', 'PPAR', 'alpha)', and, gamma, '(', 'gamma),', liver, 'X', receptor, alpha, '(', 'LXR', 'alpha),', farnesoid, 'X', receptor, '(', 'FXR),', glucocorticoid, receptor, '(', 'GR),', retinoid, 'X', receptor, alpha, '(', 'RXR', 'alpha),', hepatocyte]), verbo([nuclear]), complemento([factor, 1, alpha, '(', 'HNF1', 'alpha)', and, 4, alpha, '(', 4, 'alpha),', and, nuclear, factor, 'E2-related', factor, 2, '(', 'Nrf2)', transcription, factors])]). relacion([sujeto(['The', multivariate, approach, presented, in, this, study, should, aid, in, predicting, signalling, pathways, that]), verbo([participate]), complemento([either, directly, or, indirectly, in, regulating, hepatic, drug, disposition])]). relacion([sujeto(['Cytokines', such, as, tumor, necrosis, factor, alpha, '(', 'TNF-alpha)', and, interleukin, 1, beta, '(', 'IL-1', 'beta)', are, attributed, to]), verbo([mediate]), complemento([this, 'regulation,', but, their, particular, contribution, in, vivo, is, still, unknown])]). relacion([sujeto(['Thus,', we, studied, the, molecular, mechanisms, by, which, 'Ntcp,', 'Oatp1,', 'Oatp2,', and, 'Mrp2', are]), verbo([regulated]), complemento([by, proinflammatory, cytokines, during, liver, injury])]). relacion([sujeto(['Messenger', 'RNA', '(', 'mRNA)', levels, of, transporters, and]), verbo([binding]), complemento([activities, as, well, as, nuclear, protein, levels, of, 'Ntcp,', 'Oatp2,', and, 'Mrp2', transactivators, were, determined, 20, to, 24, hours, later])]). relacion([sujeto(['In', contrast, to, 'IL-1', 'beta,', 'TNF-alpha', inactivation, alone, fully]), verbo([prevented]), complemento(['down-regulation', of, 'Ntcp,', 'Oatp1,', and, 'Oatp2', mRNA, as, well, as, reduced, binding, activity, of, hepatocyte, nuclear, factor, 1, '(', 'HNF-1)', in, 'CCl(4)-induced', toxic, injury])]). relacion([sujeto(['In', 'endotoxemia,', 'down-regulation', of, 'Mrp2,', and, partially, in, case, of, 'Ntcp,', could, be]), verbo([prevented]), complemento([by, 'IL-1', beta, but, not, 'TNF-alpha', blockade])]). relacion([sujeto(['However,', inactivation, of, either, cytokine]), verbo([led]), complemento([to, preservation, of, 'HNF1', and, partially, of, retinoid, 'X', 'receptor/retinoic', acid, receptor, '(', 'RXR/RAR)', binding, activity])]). relacion([sujeto(['No', effect, of, anticytokines, was, seen, on, pregnane, 'X', receptor, '(', 'PXR)', and, constitutive, androstane, receptor, '(', 'CAR)']), verbo([binding]), complemento([activity, as, well, as, nuclear, protein, mass])]). relacion([sujeto(['Expression', of, the, 'MRP3', gene, is]), verbo([increased]), complemento([during, pathological, states, associated, with, elevated, bile, acid, concentrations, indicating, a, role, for, this, transporter, in, adaptive, and, homeostatic, bile, acid, metabolism])]). relacion([sujeto(['Activation', of, the, 'Mrp3', promoter, in, response, to, 'VD3,', 'RA,', or, 'LCA,', as, well, as]), verbo([binding]), complemento([of, 'VDR/RXR', 'heterodimers,', was, attenuated, substantially, by, mutation, of, this, 'VDRE'])]). relacion([sujeto(['Reduction', of, endogenous, 'VDR', expression, in, colon, adenocarcinoma, 'MCA-38', cells, by, siRNA, transfection, was]), verbo([associated]), complemento([with, reduced, constitutive, and, inducible, expression, of, the, 'Mrp3', gene])]). relacion([sujeto(['The', aryl, hydrocarbon, receptor, '(', 'AHR)', and, 'NF-E2', 'p45-related', factor, '(', 'NRF2)', are, two, distinct, transcription, factors]), verbo([involved]), complemento([in, the, regulation, of, 'drug-metabolizing', enzymes])]). relacion([sujeto(['Increasing', evidence, from, several, studies, implies, that, 'AHR', and, 'NRF2']), verbo([have]), complemento([direct, 'links,', but, the, molecular, mechanism, remains, unknown])]). relacion([sujeto(['In', this, work, we, demonstrate, for, the, first, time, that, 'Nrf2', gene, transcription, is, directly]), verbo([modulated]), complemento([by, 'AHR', activation])]). relacion([sujeto(['Finally,', we, used, chromatin, immunoprecipitation, assay, to, show, a, direct]), verbo([binding]), complemento([of, 'AHR', to, the, 'Nrf2', promoter])]). relacion([sujeto(['In', this, 'minireview,', the, role, of, various]), verbo([nuclear]), complemento([receptors, and, transcription, factors, in, the, expression, of, drug, disposition, genes, is, summarized])]). relacion([sujeto(['Specifically,', the, molecular, aspects, and, functional, impact, of, the, aryl, hydrocarbon, receptor, '(', 'AhR),']), verbo([nuclear]), complemento(['factor-E2', 'p45-related', factor, 2, '(', 'N(r)f2),', hepatocyte, nuclear, factor, 1, alpha, '(', 'HNF1alpha),', constitutive, androstane, receptor, '(', 'LAR),', pregnane, 'X', receptor, '(', 'PXR),', farnesoid, 'X', receptor, '(', 'FXR),', peroxisome, 'proliferator-activated', receptor, alpha, '(', 'PPAR(alpha)),', hepatocyte, nuclear, factor, 4, alpha, '(', 'HNF4alpha),', vitamin, 'D', receptor, '(', 'VDR),', liver, receptor, homolog, 1, '(', 'LRH1),', liver, 'X', receptor, '(', 'LXR(alpha)),', small, heterodimer, 'partner-1', '(', 'SHP-1),', and, glucocorticoid, receptor, '(', 'GR)', on, gene, expression, are, detailed])]). relacion([sujeto(['Finally,', we, discuss, some, current, topics, and, themes, in]), verbo([nuclear]), complemento(['receptor-mediated', regulation, of, drug, metabolizing, enzymes, and, drug, transporters])]). relacion([sujeto(['BACKGROUND', &, 'amp;', 'AIMS:', 'OATP8', '(', gene, 'symbol:', 'SLC21A8)', is, a, multispecific, uptake, system, for, organic, 'anions,', 'xenobiotics,', and, peptides]), verbo([expressed]), complemento([at, the, basolateral, '(', 'sinusoidal)', membrane, of, human, hepatocytes])]). relacion([sujeto(['We', investigated, whether, 'OATP8', gene, expression, is]), verbo([regulated]), complemento([by, the, nuclear, receptors, farnesoid, 'X', 'receptor/bile', acid, receptor, '(', 'FXR/BAR;', 'NR1H4),', pregnane, 'X', receptor, '(', 'PXR),', or, liver, 'X', receptor, '(', 'LXR)'])]). relacion([sujeto(['RESULTS:', 'The', bile, acid, chenodeoxycholic, acid, '(', 'CDCA),', a, ligand, of, 'FXR/BAR,', but, not, clotrimazole, or, 25, -, 'hydroxycholesterol,', ligands, of, 'PXR', or, 'LXR,', 'respectively,']), verbo([induced]), complemento(['OATP8', promoter, activity])]). relacion([sujeto(['An', inverted, hexanucleotide, repeat, motif, '(', 'IR-1', 'element)', in, the, promoter, sequence, was, shown, by, electrophoretic, mobility, shift, assays, to]), verbo([bind]), complemento([the, 'FXR', '(', 9, -, 'cis-retinoic', acid, receptor, '[', 'RXRalpha])', heterodimer])]). relacion([sujeto(['CDCA', treatment]), verbo([increased]), complemento(['OATP8', messenger, 'RNA', levels, in, human, hepatoma, 'cells,', suggesting, a, physiologic, role, for, 'FXR-mediated', 'OATP8', gene, regulation])]). relacion([sujeto(['CONCLUSIONS:', 'OATP8', gene, expression, is]), verbo([regulated]), complemento([by, bile, acids, via, 'FXR/BAR'])]). relacion([sujeto(['Induction', of, 'OATP8', could, serve, to]), verbo([maintain]), complemento([hepatic, extraction, of, xenobiotics, and, peptides, in, conditions, of, increased, intracellular, bile, acids])]). relacion([sujeto(['Major', transport, proteins]), verbo([involved]), complemento([in, the, enterohepatic, circulation, of, bile, salts, include, the, hepatocellular, bile, salt, export, pump, '(', 'BSEP,', 'ABCB11),', the, apical, 'sodium-dependent', bile, salt, transporter, '(', 'ASBT,', 'SLC10A2)', in, cholangiocytes, and, 'enterocytes,', the, 'sodium-dependent', hepatocyte, bile, salt, uptake, system, 'NTCP', '(', 'SLC10A1),', the, organic, anion, transporting, polypeptides, 'OATP-C', '(', 'SLC21A6),', 'OATP8', '(', 'SLC21A8)', and, 'OATP-A', '(', 'SLC21A3),', and, the, multidrug, resistance, protein, 'MRP3', '(', 'ABCC3)'])]). relacion([sujeto(['A', key, regulator, of, hepatocellular, bile, salt, homeostasis, is, the, bile, acid, 'receptor/farnesoid', 'X', receptor, 'FXR,', which]), verbo([activates]), complemento([transcription, of, the, 'BSEP', and, 'OATP8', genes, and, of, the, small, heterodimer, partner, 1, '(', 'SHP)'])]). relacion([sujeto(['SHP', is, a, transcriptional, repressor, that]), verbo([mediates]), complemento([bile, 'acid-induced', repression, of, the, bile, salt, uptake, systems, rat, 'Ntcp', and, human, 'OATP-C'])]). relacion([sujeto(['A']), verbo([nuclear]), complemento([receptor, that, activates, rodent, 'Oatp2', '(', 'Slc21a5)', and, human, 'MRP2', '(', 'ABCC2)', is, the, pregnane, 'X', 'receptor/steroid', 'X', receptor, 'PXR/SXR'])]). relacion([sujeto(['Intracellular', trafficking, and, membrane, insertion, of, bile, salt, transporters, is]), verbo([regulated]), complemento([by, 'lipid,', 'protein,', and, extracellular, 'signal-related', kinases, in, response, to, physiologic, stimuli, such, as, cyclic, adenosine, monophosphate, or, taurocholate])]). relacion([sujeto(['Finally,', dysfunction, of, individual, bile, salt, transporters, such, as, 'BSEP,', on, account, of, genetic, 'mutations,', steric, 'inhibition,', suppression, of, gene, 'expression,', or, disturbed, 'signaling,', is, an, important]), verbo([cause]), complemento([of, cholestatic, liver, disease])]). relacion([sujeto(['Elevated', intracellular, cyclic, 'AMP', 'levels,', which]), verbo([suppress]), complemento([the, proliferation, of, naive, 'T', cells, and, type, 1, 'T', helper, '(', 'Th1)', cells, are, a, property, of, 'T', helper, 2, '(', 'Th2)', cells, and, regulatory, 'T', cells])]). relacion([sujeto(['In', 'addition,', cyclic, 'AMP', signals]), verbo([enhance]), complemento([histone, 'H3', acetylation, at, the, 'IL-5', promoter, and, the, concerted, binding, of, 'GATA-3', and, 'NFATc', to, the, promoter])]). relacion([sujeto(['This', is, facilitated, by, direct, 'protein-protein', interactions]), verbo([involving]), complemento([the, 'C-terminal', 'Zn(2+)-finger', of, 'GATA-3', and, the, 'C-terminal', region, of, the, 'NFATc1', 'DNA', binding, domain])]). relacion([sujeto(['Because', inhibition, of, 'NFATc']), verbo([binding]), complemento([to, the, 'IL-5', promoter, in, vivo, also, affects, the, binding, of, 'GATA-3,', one, may, conclude, that, upon, induction, of, 'Th2', effector, cells, 'NFATc', recruits, 'GATA-3', to, 'Th2-type', genes])]). relacion([sujeto(['Insm1', '(', 'IA-1)', encodes, a, 'Zn-finger', factor, that, is]), verbo([expressed]), complemento([in, the, developing, nervous, system])]). relacion([sujeto(['The', transcription, factors, 'Mash1', '(', 'Ascl1),', 'Phox2a,', 'Gata3', and, 'Hand2', '(', previously, 'dHand)', control, the, differentiation, of, 'sympatho-adrenal', precursor, 'cells,', and, their, deregulated, expression, in, 'Insm1', mutant, mice, demonstrates, that, 'Insm1']), verbo([acts]), complemento([in, the, transcriptional, network, that, controls, differentiation, of, this, lineage])]). relacion([sujeto(['Pronounced', similarities, between, 'Mash1', and, 'Insm1', phenotypes, are, 'apparent,', which]), verbo([suggests]), complemento([that, 'Insm1', might, mediate, aspects, of, 'Mash1', function, in, the, 'subtype-specific', differentiation, of, 'sympatho-adrenal', precursors])]). relacion([sujeto(['Noradrenaline', is, the, major, catecholamine, produced, by, developing, 'sympatho-adrenal', cells, and, is]), verbo([required]), complemento([for, fetal, survival])]). relacion([sujeto(['We', demonstrate, that, the, fetal, lethality, of, 'Insm1', mutant, mice, is]), verbo([caused]), complemento([by, catecholamine, 'deficiency,', which, highlights, the, importance, of, 'Insm1', in, the, development, of, the, 'sympatho-adrenal', lineage])]). relacion([sujeto(['To']), verbo([gain]), complemento([a, deeper, molecular, understanding, of, the, dysfunctional, 'T cell', 'state,', we, analyzed, population, and, 'single-cell', 'RNA', profiles, of, 'CD8(+)', 'tumor-infiltrating', lymphocytes, '(', 'TILs)', and, used, genetic, perturbations, to, identify, a, distinct, gene, module, for, 'T cell', dysfunction, that, can, be, uncoupled, from, 'T cell', activation])]). relacion([sujeto(['This', distinct, dysfunction, module, is, downstream, of, intracellular, metallothioneins, that]), verbo([regulate]), complemento([zinc, metabolism, and, can, be, identified, at, 'single-cell', resolution])]). relacion([sujeto(['Our', results, open, novel, avenues, for]), verbo([targeting]), complemento([dysfunctional, 'T cell', states, while, leaving, activation, programs, intact])]). relacion([sujeto(['Here,', we, demonstrate, that, 'GATA3', is, specifically]), verbo([expressed]), complemento([in, glomerular, mesangial, cells, and, plays, a, critical, role, in, the, maintenance, of, renal, glomerular, function])]). relacion([sujeto(['Newly', generated, 'Gata3', hypomorphic, mutant, mice, exhibited, neonatal, lethality]), verbo([associated]), complemento([with, severe, renal, hypoplasia])]). relacion([sujeto(['We']), verbo([found]), complemento([that, the, 662, -, kb, 'Gata3', 'YAC', transgene, recapitulated, 'Gata3', expression, in, the, renal, tubules, but, failed, to, direct, sufficient, 'GATA3', activity, to, mesangial, cells])]). relacion([sujeto(['Renal', glomeruli, of, the, 'G3YR', mice, had, significantly, reduced, amounts, of, 'platelet-derived', growth, factor, receptor, '(', 'PDGFR),', which, is, known, to]), verbo([participate]), complemento([in, the, development, and, maintenance, of, glomerular, mesangial, cells])]). relacion([sujeto(['Recent', studies]), verbo([have]), complemento([revealed, various, distinct, 'memory-type', 'Th2', cell, 'subsets,', one, of, which, produces, a, substantial, amount, of, 'IFNγ', in, addition, to, 'Th2', 'cytokines,', however, it, remains, unclear, precisely, how, these, 'Th2', cells, produce, 'IFNγ'])]). relacion([sujeto(['We', herein, show, that, phosphorylation, of, 'Gata3', at, 'Ser308,', 'Thr315', and, 'Ser316']), verbo([induces]), complemento([dissociation, of, a, histone, deacetylase, 'Hdac2', from, the, 'Gata3/Chd4', repressive, complex, in, 'Th2', cells])]). relacion([sujeto(['We', also, identify, 'Akt1', as, a, 'Gata3-phosphorylating', 'kinase,', and, the, activation, of, 'Akt1']), verbo([induces]), complemento([derepression, of, 'Tbx21', and, 'Ifng', expression, in, 'Th2', cells])]). relacion([sujeto(['Development', of, human, placenta]), verbo([involves]), complemento([the, invasion, of, trophoblast, cells, from, anchoring, villi, into, the, maternal, decidua])]). relacion([sujeto(['Placental', transcription, factor, 'GCM1']), verbo([regulates]), complemento([trophoblast, cell, invasion, via, transcriptional, activation, of, 'HtrA4', 'gene,', which, encodes, a, serine, protease, enzyme])]). relacion([sujeto(['The', 'GATA3', transcription, factor]), verbo([regulates]), complemento([trophoblast, cell, differentiation, and, is, highly, expressed, in, invasive, murine, trophoblast, giant, cells])]). relacion([sujeto(['The', regulation, of, trophoblastic, invasion, by, 'GCM1', may]), verbo([involve]), complemento([novel, cellular, factors])]). relacion([sujeto(['Here', we, show, that, 'GATA3']), verbo([interacts]), complemento([with, 'GCM1', and, inhibits, its, activity, to, suppress, trophoblastic, invasion])]). relacion([sujeto(['Interestingly,', 'GATA3']), verbo([interacts]), complemento([with, 'GCM1,', but, not, the, 'GCM2', 'homologue,', through, the, 'DNA-binding', domain, and, first, transcriptional, activation, domain, in, 'GCM1', and, the, transcriptional, activation, domains, and, zinc, finger, 1, domain, in, 'GATA3'])]). relacion([sujeto(['While', 'GATA3', did, not, affect, 'DNA-binding', activity, of, 'GCM1,', it]), verbo([suppressed]), complemento([transcriptional, activity, of, 'GCM1', and, therefore, 'HtrA4', promoter, activity])]). relacion([sujeto(['Correspondingly,', 'GATA3', knockdown, elevated, 'HtrA4', expression, in, 'BeWo', and, 'JEG-3', trophoblast, cell, lines, and]), verbo([enhanced]), complemento([the, invasion, activities, of, both, lines])]). relacion([sujeto(['GATA3', is, a, 'zinc-binding', transcription, factor, that]), verbo([regulates]), complemento([the, differentiation, of, many, human, tissue, 'types,', including, the, mammary, gland])]). relacion([sujeto(['Although', 'GATA3', labeling, is, highest, in, estrogen, 'receptor-positive', 'carcinomas,', it, also, labels, estrogen, 'receptor-negative', carcinomas, and, thus]), verbo([has]), complemento([particular, diagnostic, utility, in, the, setting, of, 'triple-negative', breast, 'carcinomas,', which, are, typically, negative, for, other, 'mammary-specific', markers])]). relacion([sujeto(['GATA-3,', a, member, of, the, 'GATA', family, of, 'zinc-finger', 'DNA']), verbo([binding]), complemento(['proteins,', and, 'FOXA1,', a, member, of, the, forkhead, transcription, factor, 'family,', are, both, associated, with, estrogen, receptor, expression])]). relacion([sujeto(['Both', 'GATA-3', and, 'FOXA1', are, useful, markers, for, breast, 'carcinoma,', but, their, expression, in, the, different, breast, cancer, subtypes, and, other, neoplasms]), verbo([has]), complemento([not, been, thoroughly, evaluated])]). relacion([sujeto(['Hypoparathyroidism,', 'deafness,', and, renal, dysplasia, '(', 'HDR)', syndrome, is, a, rare, autosomal, dominant, disorder]), verbo([caused]), complemento([by, mutations, in, the, zinc, finger, transcription, factor, 'gene,', 'GATA3'])]). relacion([sujeto(['GATA3']), verbo([has]), complemento([2, zinc, finger, 'domains,', which, play, an, important, role, in, the, increase, in, target, gene, transcription, activity])]). relacion([sujeto(['The', structure, prediction, showed, that, it]), verbo([caused]), complemento([a, conformation, change, in, this, junction, 'area,', affecting, the, spatial, position, of, the, zinc, fingers])]). relacion([sujeto(['Functional', analysis, of, this, mutant, protein, using, an, in, vitro, luciferase, reporter, assay, system, confirmed, that, the, mutation, abolished, the]), verbo([enhancing]), complemento([effects, of, 'wild-type', 'GATA3', on, the, promoter, activity, of, the, consensus, 'GATA', responsive, element, and, that, of, human, 'PTH', gene])]). relacion([sujeto(['GATA', transcription, factors, are, zinc, finger, 'DNA']), verbo([binding]), complemento([proteins, that, regulate, transcription, during, development, and, cell, differentiation])]). relacion([sujeto(['GATA1', is]), verbo([required]), complemento([for, the, erythroid, and, megakaryocytic, commitment, during, hematopoiesis])]). relacion([sujeto(['GATA2', is, crucial, for, the, proliferation, and, survival, of, early, hematopoietic, 'cells,', and, is, also]), verbo([involved]), complemento([in, lineage, specific, transcriptional, regulation, as, the, dynamic, partner, of, 'GATA1'])]). relacion([sujeto(['As', a, 'result,', mutations, in, genes, encoding, the, 'GATA', transcription, factors, or, alteration, in, the, protein, expression, level, or, their, function]), verbo([have]), complemento([been, linked, to, a, variety, of, human, hematologic, disorders])]). relacion([sujeto(['The', transcription, factor, 'GATA1', helps]), verbo([regulate]), complemento([the, expression, of, thousands, of, genes, involved, in, blood, 'development,', by, binding, to, single, or, double, 'GATA', sites, on, 'DNA'])]). relacion([sujeto(['It', was, recently, 'suggested,', based, on, studies, of, the, closely, related, protein, 'GATA3,', that, 'GATA-mediated', looping, may]), verbo([involve]), complemento([interactions, of, each, of, two, zinc, fingers, '(', 'ZF)', with, distantly, spaced, 'DNA', elements])]). relacion([sujeto(['Here', we, present, a, structure, of, the, 'GATA1', 'ZF', region]), verbo([bound]), complemento([to, pseudopalindromic, double, 'GATA', site, 'DNA,', which, is, structurally, equivalent, to, a, 'recently-solved', 'GATA3-DNA', complex])]). relacion([sujeto(['However,', extensive, analysis, of, 'GATA1-DNA']), verbo([binding]), complemento([indicates, that, although, the, 'N-terminal', 'ZF', '(', 'NF)', can, modulate, 'GATA1-DNA', 'binding,', under, physiological, conditions, the, 'NF', binds, 'DNA', so, poorly, that, it, cannot, play, a, direct, role, in, 'DNA-looping'])]). relacion([sujeto(['Rather,', the, ability, of, the, 'NF', to, stabilize, transcriptional, complexes, through, 'protein-protein', 'interactions,', and, thereby]), verbo([recruit]), complemento([looping, factors, such, as, 'Ldb1,', provides, a, more, compelling, model, for, 'GATA-mediated', looping])]). relacion([sujeto(['In', the, immune, 'system,', zbtb16, expression, is, only]), verbo([found]), complemento([in, innate, cells])]). relacion([sujeto(['Conventional', 'T', cells, that, ectopically]), verbo([express]), complemento(['PLZF', spontaneously, acquire, an, 'activated,', effector, phenotype])]). relacion([sujeto(['Activation']), verbo([induced]), complemento([expression, of, lineage, defining, transcription, factors, such, as, 'T-bet,', 'FoxP3,', 'RORγt,', 'GATA3', and, others, is, essential, for, naïve, 'T', cell, differentiation, into, effector, 'T', cells])]). relacion([sujeto(['Surprisingly,', we]), verbo([found]), complemento([that, 'PLZF', was, stably, repressed, in, 'non-innate', 'T', cells, and, that, 'TCR-mediated', signaling, was, not, sufficient, to, induce, 'PLZF', in, conventional, 'T', cells])]). relacion([sujeto(['The', inactivated, state, of, 'PLZF', was, stably]), verbo([maintained]), complemento([in, mature, 'T', 'cells,', even, under, inflammatory, conditions, imposed, by, bacterial, infection])]). relacion([sujeto(['Collectively,', our, data, show, 'that,', in, contrast, to, multiple, recent, 'reports,', 'PLZF', expression, is, highly, specific, to, innate, 'T', cells, and, cannot, be]), verbo([induced]), complemento([in, conventional, 'T', cells, via, 'TCR-mediated', activation, or, inflammatory, challenge])]). relacion([sujeto(['Several', transcription, factors]), verbo([have]), complemento([been, found, to, have, critical, functions, in, the, development, of, both, 'ILC2s', and, 'T', cells])]). relacion([sujeto(['We']), verbo([report]), complemento([here, that, 'Bcl11b,', a, transcription, factor, essential, in, 'T', cell, lineage, commitment, and, 'maintenance,', is, specifically, expressed, in, progenitors, committed, to, the, 'ILC2', lineage, and, is, required, for, 'ILC2', development])]). relacion([sujeto(['The', 'Bcl11b', gene, is]), verbo([expressed]), complemento([in, '∼28%', of, 'ILC', progenitors, '(', 'ILCPs;', common, helper, innate, lymphoid, progenitors, or, 'ILCPs', expressing, either, 'ID2', or, promyelocytic, leukemia, zinc, 'finger,', 'respectively)'])]). relacion([sujeto(['Inactivation', of, 'Bcl11b']), verbo([causes]), complemento([a, complete, loss, of, 'ILC2', development, from, hematopoietic, 'progenitors,', which, is, confirmed, upon, immune, challenge, with, either, papain, administration, or, influenza, virus, infection])]). relacion([sujeto(['Haploinsufficiency', of, the, 'Gata3', 'gene,', which, encodes, a, 'zinc-finger', transcription, 'factor,', is]), verbo([associated]), complemento([with, the, disorder, 'hypoparathyroidism,', 'deafness,', and, renal, dysplasia, '(', 'HDR)', syndrome, in, humans])]). relacion([sujeto(['In', this, 'study,', we, show, that, 'Gata3']), verbo([activates]), complemento([transcription, of, parathyroid, hormone, '(', 'PTH),', which, is, secreted, from, parathyroid, glands, and, is, critical, for, regulating, serum, calcium, and, phosphate, homeostasis])]). relacion([sujeto(['Gata3']), verbo([interacted]), complemento([with, 'Gcm2', and, 'MafB,', two, known, transcriptional, regulators, of, parathyroid, 'development,', and, synergistically, stimulated, the, 'PTH', promoter])]). relacion([sujeto(['An', 'SP1-binding', element, '(', 'GC', 'box)', located, within, the, 'PTH-promoter', proximal, region, was, critical, for]), verbo([activating]), complemento([transcription, by, 'Gata3'])]). relacion([sujeto(['In', 'addition,', the, ubiquitous, transcription, factor, 'SP1', also]), verbo([interacted]), complemento([with, 'Gata3', as, well, as, 'MafB', and, 'Gcm2,', and, 'HDR', 'syndrome-associated', 'Gata3', mutants, were, defective, in, activating, the, 'PTH', promoter])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, 'Gata3', is, a, critical, regulator, of, 'PTH', gene, expression])]). relacion([sujeto(['Immature', placentas, were, characterized, by, 'strong,', diffuse]), verbo([nuclear]), complemento(['GATA3', staining])]). relacion([sujeto(['The', extent, of, 'GATA3', expression, varied, between, immature, and, mature, 'placentas,']), verbo([suggesting]), complemento([a, role, in, trophoblast, maturation])]). relacion([sujeto(['Paraquat', '(', 'PQ),', one, of, the, most, widely, used, 'herbicides,']), verbo([has]), complemento([been, used, for, several, decades, in, agriculture])]). relacion([sujeto(['Some', studies]), verbo([suggest]), complemento([that, 'PQ', has, effects, on, the, immune, system])]). relacion([sujeto(['Moreover,', previous, studies]), verbo([have]), complemento([shown, that, 'PQ', imparted, some, immunosuppressive, effects])]). relacion([sujeto(['Given', that, 'PQ', was, expected, to]), verbo([induce]), complemento([an, immunosuppressive, 'effect,', it, was, hypothesized, that, a, gene, involved, in, cellular, metal, ion, 'homeostasis,', 'metallothionein-1', '(', 'MT-1),', could, play, an, important, role, in, this, outcome])]). relacion([sujeto(['The', results, showed, that, 'PQ', treatments]), verbo([led]), complemento([to, increased, 'MT', expression, in, several, organs, '(', 'liver,', 'kidneys,', 'testes)', and, in, 'splenocytes,', caused, a, reduction, of, both, free, zinc, ions, in, sera, and, in, free, intracellular, 'zinc,', and, reduced, the, expression, of, 'GATA-3,', a, 'zinc-finger', transcription, factor, important, for, maturation, and, activity, of, 'T-cells', and, 'NK', cells])]). relacion([sujeto(['These', results]), verbo([provide]), complemento([a, basis, for, a, new, molecular, mechanism, to, describe, potential, immunosuppressive, effects, of, 'PQ', in, vivo])]). relacion([sujeto(['The', mammalian]), verbo([target]), complemento([of, rapamycin, '(', 'mTOR)', senses, and, incorporates, different, environmental, cues, via, the, two, signaling, complexes, mTOR, complex, 1, '(', 'mTORC1)', and, mTORC2])]). relacion([sujeto(['This', is]), verbo([caused]), complemento([by, decreased, proliferation, of, stage, 1, iNKT, cells, and, poor, development, through, subsequent, stages])]). relacion([sujeto(['Functionally,', iNKT, cells, devoid, of, mTORC2, signaling, showed, reduced, number, of, 'IL-4-expressing', 'cells,', which, correlated, with, a]), verbo([decrease]), complemento([in, the, transcription, factor, 'GATA-3-expressing', cells])]). relacion([sujeto(['However,', promyelocytic, leukemia, 'zinc-finger', '(', 'PLZF),', a, critical, transcription, factor, for, iNKT, cell, 'development,', is]), verbo([expressed]), complemento([at, a, similar, level, in, 'mTORC2-deficient', iNKT, cells, compared, with, that, in, the, wild, type, iNKT, cells])]). relacion([sujeto(['Thus,', our, study]), verbo([reveals]), complemento([the, 'PLZF-independent', mechanisms, of, the, development, and, function, of, iNKT, cells, regulated, by, mTORC2])]). relacion([sujeto(['In', our, previous, 'study,', we, showed, that, signaling, lymphocytic, activation, molecule]), verbo([associated]), complemento([protein, '(', 'SAP)', is, essential, for, the, development, of, type, 'II', 'NKT', cells])]). relacion([sujeto(['Furthermore,', we, showed, that, 'SAP']), verbo([regulates]), complemento([type, 'II', 'NKT-cell', development, by, controlling, early, growth, response, 2, protein, and, promyelocytic, leukemia, zinc, finger, expression])]). relacion([sujeto(['The', impaired, 'IL-4', production, by, 'SAP-deficient', 24, αβ, 'T', cells, was]), verbo([associated]), complemento([with, reduced, 'IFN', regulatory, factor, 4, and, 'GATA-3', induction, following, 'TCR', stimulation])]). relacion([sujeto(['Collectively,', these, data]), verbo([suggest]), complemento([that, 'SAP', is, critical, for, regulating, type, 'II', 'NKT', cell, responses])]). relacion([sujeto(['Aberrant', responses, of, these, 'T', cells, may, contribute, to, the, immune, dysregulation, observed, in, 'X-linked', lymphoproliferative, disease]), verbo([caused]), complemento([by, mutations, in, 'SAP'])]). relacion([sujeto(['Recent', evidence]), verbo([suggests]), complemento([the, involvement, of, sex, hormone, receptors, in, bladder, cancer, 'initiation,', while, precise, functions, of, androgens, and, estrogens, in, the, carcinogenesis, step, remain, poorly, understood])]). relacion([sujeto(['We', recently]), verbo([found]), complemento(['down-regulation', of, 'GATA3,', a, 'zinc-finger', transcription, factor, and, a, new, urothelial, 'marker,', in, bladder, 'cancer,', which, also, correlated, with, expression, status, of, androgen, receptor, '(', 'AR)', and, estrogen, receptors, '(', 'ERs)'])]). relacion([sujeto(['We', here, assessed, whether, 'GATA3']), verbo([acted]), complemento([as, a, suppressor, of, bladder, tumorigenesis, and, sex, hormones, exerted, an, influence, on, 'GATA3', in, 'non-neoplastic', urothelial, cells])]). relacion([sujeto(['Androgen', '(', 'R1881,', 'dihydrotestosterone)', treatment, in, 'SVHUC', immortalized, normal, urothelial, cells, stably]), verbo([expressing]), complemento(['AR', '(', 'SVHUC-AR)', decreased, 'GATA3', expression, at, both, mRNA, and, protein, 'levels,', which, was, abolished, by, 'anti-androgens'])]). relacion([sujeto(['Conversely,', 17, 'β-estradiol', treatment]), verbo([increased]), complemento([it, in, 'SVHUC-control', endogenously, expressing, 'ERβ'])]). relacion([sujeto(['GATA3', levels, were, also]), verbo([found]), complemento([to, be, higher, in, intact, female, mouse, bladders, compared, with, intact, 'males,', and, 'orchiectomy/ovariectomy', 'augmented/reduced', 'GATA3', 'expression,', 'respectively,', which, was, at, least, partially, restored, by, 'dihydrotestosterone/17β-estradiol', supplement])]). relacion([sujeto(['Additionally,', 'GATA3', silencing, via, short, hairpin, 'RNA', '(', 'shRNA)']), verbo([promoted]), complemento([cell, proliferation, of, 'SVHUC', with, exposure, to, a, chemical, carcinogen, 3, -, methylcholanthrene])]). relacion([sujeto(['In', vitro, transformation, assay, with, 3, -, methylcholanthrene, then, showed, a, significantly, higher, number, of, colonies, in, 'SVHUC-AR/GATA3-shRNA,', compared, with, control, 'SVHUC,', and, 'R1881', further]), verbo([induced]), complemento([colony, formation])]). relacion([sujeto(['Thus,', 'GATA3', likely]), verbo([prevented]), complemento([neoplastic, transformation, of, urothelial, cells])]). relacion([sujeto(['Furthermore,', sex, hormone, signals, contrary]), verbo([regulated]), complemento(['GATA3', in, the, bladder])]). relacion([sujeto(['The', 'zinc-finger', transcription, factor, 'GATA-3']), verbo([has]), complemento([received, much, attention, as, a, master, regulator, of, 'T', helper, 2, '(', 'Th2)', cell, 'differentiation,', during, which, it, controls, 'interleukin-4', '(', 'IL-4),', 'IL-5,', and, 'IL-13', expression])]). relacion([sujeto(['Furthermore,', during, 'thymopoiesis,', 'GATA-3', represses, 'B', cell, potential, in, early, 'T', cell, 'precursors,']), verbo([activates]), complemento(['TCR', signaling, in, 'pre-T', 'cells,', and, promotes, the, 'CD4(+)', 'T', cell, lineage, after, positive, selection])]). relacion([sujeto(['The', 'hypoparathyroidism,', deafness, and, renal, dysplasia, '(', 'HDR)', syndrome, is, an, autosomal, dominant, disorder, primarily]), verbo([caused]), complemento([by, 'GATA3', gene, mutation])]). relacion([sujeto(['We']), verbo([report]), complemento([here, a, case, that, both, of, a, 'Chinese', boy, and, his, father, had, 'HDR', syndrome, which, caused, by, a, novel, mutation, of, 'GATA3'])]). relacion([sujeto(['S172X)', with, a]), verbo([loss]), complemento([of, two, zinc, finger, domains])]). relacion([sujeto(['The', 'ZNF217', 'gene,', encoding, a, 'C2H2', zinc, finger, 'protein,', is, located, at, 20, q13, and]), verbo([found]), complemento([amplified, and, overexpressed, in, greater, than, 20, '%', of, breast, tumors])]). relacion([sujeto(['Because', 'ZNF217']), verbo([associates]), complemento([with, chromatin, modifying, 'enzymes,', we, postulate, that, 'ZNF217', functions, to, regulate, specific, gene, signaling, networks])]). relacion([sujeto(['Here,', we, present, a, 'large-scale', functional, genomic, analysis, of, 'ZNF217,', which]), verbo([provides]), complemento([insights, into, the, regulatory, role, of, 'ZNF217', in, 'MCF7', breast, cancer, cells])]). relacion([sujeto(['ChIP-seq', analysis]), verbo([reveals]), complemento([that, the, majority, of, 'ZNF217', binding, sites, are, located, at, distal, regulatory, regions, associated, with, the, chromatin, marks, 'H3K27ac', and, 'H3K4me1'])]). relacion([sujeto(['Analysis', of, 'ChIP-seq', transcription, factor]), verbo([binding]), complemento([sites, shows, clustering, of, 'ZNF217', with, 'FOXA1,', 'GATA3', and, 'ERalpha', binding, 'sites,', supported, by, the, enrichment, of, corresponding, motifs, for, the, 'ERalpha-associated', 'cis-regulatory', sequences])]). relacion([sujeto(['ERalpha', expression, highly, correlates, with, 'ZNF217', in, lysates, from, breast, tumors, '(', n, =, 15, ')', ',', and, 'ERalpha', 'co-precipitates', 'ZNF217', and, its]), verbo([binding]), complemento([partner, 'CtBP2', from, nuclear, extracts])]). relacion([sujeto(['Transcriptome', profiling, following, 'ZNF217', depletion, identifies, differentially]), verbo([expressed]), complemento([genes, 'co-bound', by, 'ZNF217', and, 'ERalpha;', gene, ontology, suggests, a, role, for, 'ZNF217-ERalpha', in, expression, programs, associated, with, 'ER+', breast, cancer, studies, found, in, the, 'Molecular', 'Signature', 'Database'])]). relacion([sujeto(['Our', 'genome-wide', 'ZNF217', data]), verbo([suggests]), complemento([a, functional, role, for, 'ZNF217', at, 'ERalpha', target, genes])]). relacion([sujeto(['The', maintenance, of, pluripotency, of, 'CSCs', under, various, pathophysiological, conditions]), verbo([requires]), complemento([a, complex, interaction, between, various, cellular, pathways, including, those, involved, in, homeostasis, and, energy, metabolism])]). relacion([sujeto(['However,', the, exact, mechanisms, that]), verbo([maintain]), complemento([the, 'CSC', pluripotency, remain, poorly, understood])]). relacion([sujeto(['In', this, 'report,', using, both, human, and, murine, models, of, 'CSCs,', we, demonstrate, that, basal, levels, of, autophagy, are]), verbo([required]), complemento([to, maintain, the, pluripotency, of, 'CSCs,', and, that, this, process, is, differentially, regulated, by, the, rate, limiting, enzyme, in, the, 'NAD(+)', synthesis, pathway, 'NAMPT', '(', nicotinamide, 'phosphoribosyltransferase)', and, the, transcription, factor, 'POU5F1/OCT4', '(', 'POU', class, 5, homeobox, 1, ')'])]). relacion([sujeto(['First,', our, data, show, that, the, pharmacological, inhibition, and, knockdown, '(', 'KD)', of, 'NAMPT', or, the, 'KD', of, 'POU5F1', in, human, 'CSCs', significantly]), verbo([decreased]), complemento([the, expression, of, pluripotency, markers, 'POU5F1,', 'NANOG', '(', 'Nanog', 'homeobox)', and, 'SOX2', '(', 'SRY-box', 2, ')', ',', and, upregulated, the, differentiation, markers, 'TUBB3', '(', tubulin, beta, 3, class, 'III),', 'CSN2', '(', casein, 'beta),', 'SPP1', '(', secreted, phosphoprotein, 1, ')', ',', 'GATA6', '(', 'GATA', binding, protein, 6, ')', ',', 'T', '(', 'T', brachyury, transcription, 'factor)', and, 'CDX2', '(', caudal, type, homeobox, 2, ')'])]). relacion([sujeto(['Interestingly,', these, 'pluripotency-regulating', effects, of, 'NAMPT', and, 'POU5F1', were, accompanied, by, contrasting, levels, of, 'autophagy,', wherein, 'NAMPT', 'KD']), verbo([promoted]), complemento([while, 'POU5F1', 'KD', inhibited, the, autophagy, machinery])]). relacion([sujeto(['Most', 'importantly,', any, deviation, from, the, basal, level, of, 'autophagy,', either]), verbo([increase]), complemento(['(', via, 'rapamycin,', serum, starvation, or, 'Tat-beclin', 1, '[', 'Tat-BECN1]', 'peptide)', or, decrease, '(', via, 'ATG7', or, 'ATG12', 'KD),', strongly, decreased, the, pluripotency, and, promoted, the, differentiation, 'and/or', senescence, of, 'CSCs'])]). relacion([sujeto(['LincRNAs', are, less, evolutionarily, 'conserved,', less, 'abundant,', and, more, 'tissue-specific,']), verbo([suggesting]), complemento([that, their, 'pre-', and, 'post-transcriptional', regulation, is, different, from, that, of, mRNAs])]). relacion([sujeto(['We']), verbo([find]), complemento([that, lincRNA, promoters, are, depleted, of, transcription, factor, '(', 'TF)', binding, 'sites,', yet, enriched, for, some, specific, factors, such, as, 'GATA', and, 'FOS', relative, to, mRNA, promoters])]). relacion([sujeto(['Surprisingly,', we]), verbo([find]), complemento([that, 'H3K9me3-a', histone, modification, typically, associated, with, transcriptional, 'repression-is', more, enriched, at, the, promoters, of, active, lincRNA, loci, than, at, those, of, active, mRNAs])]). relacion([sujeto(['The', most, discriminant, differences, between, lincRNAs, and, mRNAs]), verbo([involve]), complemento([splicing])]). relacion([sujeto(['LincRNAs', are, less, efficiently, 'spliced,', which, cannot, be, explained, by, differences, in, 'U1']), verbo([binding]), complemento([or, the, density, of, exonic, splicing, enhancers, but, may, be, partially, attributed, to, lower, 'U2AF65', binding, and, weaker, 'splicing-related', motifs])]). relacion([sujeto(['Conversely,', the, stability, of, lincRNAs, and, mRNAs, is, 'similar,', differing, only, with, regard, to, the, location, of, stabilizing, protein]), verbo([binding]), complemento([sites])]). relacion([sujeto(['Finally,', we]), verbo([find]), complemento([that, certain, transcriptional, properties, are, correlated, with, higher, evolutionary, conservation, in, both, 'DNA', and, 'RNA', motifs, and, are, enriched, in, lincRNAs, that, have, been, functionally, characterized])]). relacion([sujeto(['The', industrial, hemp, varieties, '\'', 'Yunma', 5, '\'', and, '\'', 'Bamahuoma,\'', which, demonstrate, growth, vigor, and, environmental, 'adaptability,']), verbo([have]), complemento([been, primarily, cultivated, in, 'Yunnan', and, 'Guangxi,', 'China,', 'respectively,', for, fiber, and, seeds])]). relacion([sujeto(['RNA-Seq', analysis, was, first, performed, on, leaves, of, both, varieties, sampled, at, four, time, intervals, '(', 0, ',', 2, ',', 4, ',', 6, &, 'nbsp;days)', after, treatment, with, salt, '(', 500, &, 'nbsp;mM', 'NaCl)', 'We', identified, 220, 'co-up-regulated', differentially]), verbo([expressed]), complemento([genes, '(', 'DEGs)', in, the, two, 'varieties,', while, 26, 'up-regulated', 'DEGs', and, 24, 'down-regulated', 'DEGs', were, identified, exclusively, in, the, single, varieties, after, 2, &, 'nbsp;days', of, salt, stress])]). relacion([sujeto(['Among', the, 220, 'DEGs,', we, identified, 22, transcription, 'factors,', including, key, transcription, factors]), verbo([involved]), complemento([in, salt, 'stress,', such, as, 'MYB,', 'NAC,', 'GATA,', and, 'HSF'])]). relacion([sujeto(['We', applied, gene, expression, profile, analysis, and]), verbo([found]), complemento([that, '\'', 'Yunma', 5, '\'', and, '\'', 'Bamahuoma\'', have, 'variety-specific', pathways, for, resisting, salt, stress])]). relacion([sujeto(['The', 'DEGs', that, were, 'co-expressed', in, both, varieties, under, stress, may]), verbo([provide]), complemento([useful, insights, into, the, tolerance, of, cultivated, hemp, and, other, bast, fiber, crops, to, saline, soil, conditions])]). relacion([sujeto(['RESULTS', 'Two', thousands, and, sixteen, kidney, transplantations]), verbo([have]), complemento([been, carried, out, from, 1968, -, 2015])]). relacion([sujeto(['CONCLUSIONS', 'The', application, of, the, new, 'WHO', 2016, classification]), verbo([has]), complemento([importance, as, it, identifies, new, '(', 18, '%', of, 'tumors)', morphotypes, that, are, likely, to, behave, in, a, less, aggressive, fashion])]). relacion([sujeto(['In', addition, to]), verbo([providing]), complemento([energy, and, constituting, cell, 'membrane,', fatty, acids, also, play, an, important, role, in, adipocyte, differentiation, and, lipid, metabolism])]). relacion([sujeto(['As', an, important, member, of, monounsaturated, fatty, 'acids,', 'oleate,', together, with, other, 'components,', is, widely, used, to]), verbo([induce]), complemento([chicken, preadipocyte, differentiation])]). relacion([sujeto(['However,', it, is, not, clear, whether, oleate, alone, can]), verbo([induce]), complemento([chicken, preadipocyte, differentiation])]). relacion([sujeto(['After', treatment, of, oleate, on, chicken, 'preadipocytes,', apparent, lipid, droplet, formation, and, lipid, accumulation, were, 'observed,', accompanied, by]), verbo([increasing]), complemento([expression, of, 'PPARγ', '(', peroxisome, 'proliferator-activated', 'receptor-γ)', and, 'AFABP', '(', adipocyte, fatty, 'acid-binding', 'protein),', but, decreasing, level, of, 'GATA2', '(', 'GATA-binding', protein, 2, ')'])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, exogenous, oleate, alone, can, act, as, an, inducer, of, preadipocyte, differentiation, into, adipocytes])]). relacion([sujeto(['T', cells]), verbo([have]), complemento([been, identified, as, key, players, in, the, pathogenesis, of, type, 1, diabetes])]). relacion([sujeto(['The', expression, of, 'GATA-3', was, relatively, similar, in, patients, and, 'controls;', 'however,', 'IL-4', mRNAs, were, significantly]), verbo([increased]), complemento([in, the, 'PBMCs', from, patients, as, compared, with, normal, controls, '(', 'p<0'])]). relacion([sujeto(['In', 'addition,', a, marked]), verbo([increase]), complemento([in, plasma, 'IL-4', levels, were, observed, in, patient, group, compared, with, controls, '(', 'p<0'])]). relacion([sujeto(['To', the, 'contrary,', 'IFN-γ', protein, levels, were]), verbo([decreased]), complemento([in, patients, in, comparison, with, controls, '(', 'p<0'])]). relacion([sujeto(['These', data]), verbo([suggest]), complemento([additional, implications, of, the, role, of, 'Th1/Th2', imbalance, for, the, immunopathogenesis, of, type, 1, diabetes])]). relacion([sujeto(['The', major, cellular, and, molecular, players]), verbo([regulating]), complemento([this, important, network, have, been, identified])]). relacion([sujeto(['In', terms, of, therapeutic, 'intervention,', cytokine, and, 'cytokine-receptor', pathways]), verbo([have]), complemento([been, given, major, 'attention,', since, these, molecules, are, relatively, easily, accessible, for, a, blockade, through, monoclonal, 'antibodies,', and, a, number, of, positive, clinical, results, support, this, concept])]). relacion([sujeto(['However,']), verbo([targeting]), complemento([events, controlling, the, 'type-2', immunity, network, upstream, of, selective, cytokine, pathways, would, be, equally, attractive])]). relacion([sujeto(['Type-2', immunity, is]), verbo([regulated]), complemento([through, a, delicate, interplay, of, several, transcription, factors, '(', including, 'GATA-3,', 'STAT-6,', 'NFAT,', 'IRF4,', 'c-maf),', with, 'GATA-3', as, master, regulator, in, this, regard])]). relacion([sujeto(['Since', transcription, factors, are, intracellularly, located, they, cannot, be, directly]), verbo([targeted]), complemento([by, monoclonal, antibodies])]). relacion([sujeto(['For', intracellular, 'targets,', antisense, technologies, such, as, antisense, 'DNA', and, siRNA]), verbo([have]), complemento([been, shown, to, be, a, promising, 'approach,', and, have, recently, made, major, advances, towards, clinical, application])]). relacion([sujeto(['A', total, of, 212, alleles, were, detected, for, the, 18, autosomal, 'STR', loci, among, 528, 'Guangdong', 'Han', 'individuals,', and, 431, haplotypes, were]), verbo([found]), complemento([for, 14, 'Y-STRs', among, 452, unrelated, males])]). relacion([sujeto(['General', amino, acid, permease, 'Gap1p', is, response, of, aromatic, amino, acids, 'transportation,', and, 'GATA', transcription, factors, 'Gln3p', and, 'Gat1p']), verbo([regulate]), complemento([the, transcription, of, permease, gene, and, catabolic, enzyme, genes, for, nitrogen, sources, and, aromatic, amino, acids, utilization])]). relacion([sujeto([cerevisiae, haploid, strain, 'YS58,', 2, -, 'PE', synthesis, levels, of, recombinant, strains]), verbo([increased]), complemento([54, '%', or, 40, '%', than, that, of, the, control, 'strain,', which, suggested, that, higher, 'Gln3p', activity, in, yeast, has, positive, regulation, effect, on, 2, -, 'PE', biosynthesis, via, 'Ehrlich', pathway])]). relacion([sujeto(['The', recombinant, strains, with, 'over-expression', of, 'GAT1', gene, from, 'MT2', or, 'YS58', also, 'up-regulated', 'Ehrlich', pathway, for, 2, -, 'PE', biosynthesis, and]), verbo([increased]), complemento([2, -, 'PE', production])]). relacion([sujeto(['Similarly,', when, 'GAP1', gene, respectively, from, 'MT2', or, 'YS58', was, 'over-expressed,', 2, -, 'PE', yield, was, improved, 'obviously,']), verbo([suggesting]), complemento([that, 'GAP1', 'over-expressing', in, yeast, also, promoted, 'Ehrlich', pathway, to, produce, 2, -, 'PE'])]). relacion([sujeto(['Among', these, regulatory, 'factors,', 'Gln3p', of, industrial, yeast, strain, 'MT2']), verbo([caused]), complemento([stronger, regulation, on, target, genes, than, that, of, haploid, strain, 'YS58,', which, might, be, due, to, the, differences, in, translational, efficiency, or, nuclear, localization, of, each, 'Gln3p,', or, due, to, their, different, spatial, structures, and, binding, domains])]). relacion([sujeto(['This']), verbo([report]), complemento([presents, a, 16, -, 'year-old', female, with, preauricular, 'pilomatricoma,', located, beneath, the, overlying, skin, of, the, temporomandibular, region])]). relacion([sujeto(['They', usually, present, 'as,', 'asymptomatic,', subcutaneous, 'masses;', although, symptomatic, cases]), verbo([have]), complemento([been, reported])]). relacion([sujeto(['Pediatric', dentists, should, be, aware, of, the, condition, and, consider, it, in, the, differential, diagnosis, of, pediatric, conditions]), verbo([involving]), complemento([the, temporomandibular, joint])]). relacion([sujeto(['SUVmean,', 'MTV', and, 'TLG', were]), verbo([found]), complemento([statistically, significant, after, multivariate, analysis])]). relacion([sujeto(['Testis', and, central, nervous, system, lymphomas]), verbo([have]), complemento([higher, recurrence, rate, '(', 62.5, '%', ',', 73, '%', ',', 'respectively)'])]). relacion([sujeto(['Platelet-rich', plasma, '(', 'PRP)', is, an, autologous, concentration, of, human, platelets, contained, in, a, small, volume, of, plasma, and]), verbo([has]), complemento([recently, been, shown, to, accelerate, rejuvenate, aging, skin, by, various, growth, factors, and, cell, adhesion, molecules])]). relacion([sujeto(['In', the, 'MOD', of, 'PRP,', 89.05, percent, improvement, was]), verbo([found]), complemento([when, 'MOD', of, 'PRP', was, compared, with, 'MOD', of, 'pre-treatment'])]). relacion([sujeto(['PRP']), verbo([increases]), complemento([dermal, collagen, levels, not, only, by, growth, 'factors,', but, also, by, skin, needling, '(', the, mesotherapy, technique, '\'', point, by, 'point\')'])]). relacion([sujeto(['Histone', gene, expression, is]), verbo([regulated]), complemento([in, a, cell, 'cycle-dependent', 'manner,', with, a, peak, at, 'S', 'phase,', which, is, crucial, for, cell, division, and, genome, integrity])]). relacion([sujeto(['However,', the, detailed, mechanisms, by, which, expression, of, histone, genes, are, tightly]), verbo([regulated]), complemento([remain, largely, unknown])]). relacion([sujeto(['Fission', yeast, 'Ams2,', a, 'GATA-type', zinc, finger, 'motif-containing', 'factor,', is]), verbo([required]), complemento([for, activation, of, 'S', 'phase-specific', core, histone, gene, transcription])]). relacion([sujeto(['Here', we]), verbo([report]), complemento([the, molecular, characterisation, of, 'Ams2'])]). relacion([sujeto(['We', show, that, the, zinc, finger, motif, in, 'Ams2', is, necessary, to]), verbo([bind]), complemento([the, histone, gene, promoter, region, and, to, activate, histone, gene, transcription])]). relacion([sujeto(['An', 'N-terminal', region, of, 'Ams2']), verbo([acts]), complemento([as, a, 'self-interaction', domain])]). relacion([sujeto(['Intriguingly,', 'N-terminally', truncated, 'Ams2']), verbo([binds]), complemento([to, the, histone, gene, 'promoters,', but, does, not, fully, activate, histone, gene, transcription])]). relacion([sujeto(['These', observations, imply, that, 'Ams2', 'self-interactions', are]), verbo([required]), complemento([for, efficient, core, histone, gene, transcription])]). relacion([sujeto(['Moreover,', we, show, that, 'Ams2']), verbo([interacts]), complemento([with, 'Teb1,', which, itself, binds, to, the, core, histone, gene, promoters])]). relacion([sujeto([',', claudin, '(', 'CLDN)7,', 'CLDN4', and, 'CLDN3]', were]), verbo([associated]), complemento([with, cell, adhesion, and, digestion])]). relacion([sujeto([',', 'MAD1', mitotic]), verbo([arrest]), complemento([deficient, like, 1, ',', cyclin, '(', 'CCN)B1,', 'CCNB2', and, 'CCNE1]', were, associated, with, the, cell, cycle, and, the, regulation, of, cell, 'proliferation,', while, 'GNCA-unique', 'DEGs', '(', e])]). relacion([sujeto([',', 'GATA']), verbo([binding]), complemento([protein, 6, and, hyaluronoglucosaminidase, 1, ')', were, implicated, in, cell, death])]). relacion([sujeto(['These', common, 'DEGs', could, advance, our, understanding, of, the, etiology, of, gastric, 'cancer,', while, the, unique, 'DEGs', in, 'GCA', and, 'GNCA', could, better, define, the, properties, of, specific, cancers, and]), verbo([provide]), complemento([potential, biomarkers, for, 'diagnosis,', prognosis, or, therapy])]). relacion([sujeto(['Aberrant', expression, of, the, sodium, channel, gene, '(', 'SCN5A)']), verbo([has]), complemento([been, proposed, to, disrupt, cardiac, action, potential, and, cause, human, cardiac, 'arrhythmias,', but, the, mechanisms, of, 'SCN5A', gene, regulation, and, dysregulation, still, remain, largely, unexplored])]). relacion([sujeto(['To']), verbo([gain]), complemento([insight, into, the, transcriptional, regulatory, networks, of, 'SCN5A,', we, surveyed, the, promoter, and, first, intronic, regions, of, the, 'SCN5A', 'gene,', predicting, the, presence, of, several, binding, sites, for, 'GATA', transcription, factors, '(', 'TFs)'])]). relacion([sujeto(['Gene', reporter, experiments, show, 'GATA4', and, 'GATA5', synergism, in, the, activation, of, the, 'SCN5A', 'promoter,', and, its, dependence, on, predicted, 'GATA']), verbo([binding]), complemento([sites])]). relacion([sujeto(['GATA4', and, 'GATA6', mRNAs, are, robustly]), verbo([expressed]), complemento([in, 'fresh-frozen', human, left, ventricle, samples, as, measured, by, highly, sensitive, droplet, digital, 'PCR', '(', 'ddPCR)'])]). relacion([sujeto(['Our', studies]), verbo([suggest]), complemento([that, 'GATA5', but, especially, 'GATA4', are, main, contributors, to, 'SCN5A', gene, 'expression,', thus, providing, a, new, paradigm, of, 'SCN5A', expression, regulation, that, may, shed, new, light, into, the, understanding, of, cardiac, disease])]). relacion([sujeto(['Photodynamic', therapy, '(', 'PDT)']), verbo([has]), complemento([proven, to, be, an, effective, alternative, for, the, treatment, of, cutaneous, leishmaniasis])]). relacion([sujeto([1, ')', ;, and, in, 'PDT', treated, 'animals,', we, observed, an]), verbo([increase]), complemento([in, 'IFN-γ', and, 'T-bet', mRNA, '(', 'p=0'])]). relacion([sujeto(['There', was, a, significant, reduction, in, mRNA, expression, of, 'IL-22']), verbo([associated]), complemento([with, an, increased, expression, of, 'IL-27', mRNA, in, the, animals, treated, with, light, only, '(', p, =, 0.0001, ')'])]). relacion([sujeto([5, -, 'ALA']), verbo([associated]), complemento([with, photodynamic, therapy, promotes, a, reduction, in, parasite, load, and, an, increased, expression, of, 'IFN-γ', and, 'T-bet', mRNA])]). relacion([sujeto(['A', broaden, 'ovarian-like', differentiation, was]), verbo([found]), complemento([in, half, eutopic, and, all, ectopic, endometriosis, with, aberrant, expression, of, transcripts, and, protein, for, the, transcription, factors, 'GATA4', and, 'GATA6', triggering, ovarian, 'differentiation,', for, the, 'FSH', receptor, '(', 'FSHR)', and, the, ovarian, hormone, 'INSL3'])]). relacion([sujeto(['Like', in, ovaries, the, 'FSHR']), verbo([induced]), complemento(['aromatase,', the, key, enzyme, in, 'E2', 'production,', and, vascular, factors, in, 'EEC'])]). relacion([sujeto(['The', 'LH', receptor, '(', 'LHR)', was, also, aberrantly]), verbo([expressed]), complemento([in, a, subset, of, ectopic, endometriosis, '(', 21, '%', ')', and, induced, strongly, 'androgen-synthesizing', enzymes, and, 'INSL3', in, 'EEC,', as, in, 'ovaries,', as, well, as, endometriotic, cell, growth])]). relacion([sujeto(['The', 'ERK', pathway]), verbo([mediates]), complemento([signaling, by, both, hormones])]). relacion([sujeto(['A', positive, feedback, loop, occurred, through, 'FSHR', and, 'LHR-dependent', induction, of, 'GATA4/6', in, 'EEC,', as, in, 'ovaries,']), verbo([enhancing]), complemento([the, production, of, the, steroidogenic, cascade])]). relacion([sujeto(['This', study]), verbo([provides]), complemento([new, tools, that, might, improve, the, diagnosis, of, endometriosis, in, the, future])]). relacion([sujeto(['Vasohibin', 2, '(', 'VASH2)', is, identified, as, an, angiogenic, 'factor,', and]), verbo([has]), complemento([been, implicated, in, tumor, 'angiogenesis,', proliferation, and, 'epithelial-mesenchymal', transition, '(', 'EMT)'])]). relacion([sujeto(['We', observed, that, 'VASH2']), verbo([induced]), complemento(['EMT', 'in vitro', and, 'in vivo'])]). relacion([sujeto(['The', transforming, growth, factor, β1, '(', 'TGFβ1)', pathway, was]), verbo([activated]), complemento([by, 'VASH2,', and, expression, of, a, dominant, negative, 'TGFβ', type, 'II', receptor, could, block, 'VASH2-mediated', 'EMT'])]). relacion([sujeto(['Under', hypoxic, conditions, 'in vitro', or, 'in vivo,', we]), verbo([found]), complemento([that, 'down-regulation', of, estrogen, receptor, 1, '(', 'ESR1)', in, 'VASH2', overexpressing, 'ESR1', positive, cells, suppressed, 'E-cadherin'])]). relacion([sujeto(['These', findings]), verbo([suggest]), complemento([that, 'VASH2', drives, breast, cancer, cells, to, undergo, 'EMT', by, activation, of, the, 'TGFβ1', pathway, and, hypoxia, dependent, repression, 'GATA3-ESR1', 'pathway,', leading, to, cancer, metastasis])]). relacion([sujeto(['Allergic', asthma, is, a, worldwide]), verbo([increasing]), complemento([chronic, disease, of, the, airways, which, affects, more, than, 300, million, people])]). relacion([sujeto(['It', is]), verbo([associated]), complemento([with, increased, 'IgE,', mast, cell, 'activation,', airway, hyperresponsiveness, '(', 'AHR),', mucus, overproduction, and, remodeling, of, the, airways])]). relacion([sujeto(['Previously,', this, pathological, trait]), verbo([has]), complemento([been, associated, with, 'T', helper, type, 2, '(', 'Th2)', cells])]). relacion([sujeto(['Downstream', of, 'IL-4,', several, transcription, factors, like, signal, transducer, and, activator, of, transcription, 6, '(', 'STAT6),', interferon, regulatory, factor, 4, '(', 'IRF4),', 'GATA']), verbo([binding]), complemento([protein, 3, '(', 'GATA3),', basic, leucine, zipper, transcription, 'factor,', 'ATF-like', '(', 'BATF)', and, nuclear, factor, of, activated, 'T', cells, '(', 'NFAT)', are, activated])]). relacion([sujeto(['IL-9', is, a, pleiotropic, cytokine, that, influences, various, distinct, functions, of, different]), verbo([target]), complemento([cells, such, as, 'T', 'cells,', 'B', 'cells,', mast, cells, and, airway, epithelial, cells, by, activating, 'STAT1,', 'STAT3', and, 'STAT5'])]). relacion([sujeto(['Because', of, its, pleiotropic, 'functions,', 'IL-9']), verbo([has]), complemento([been, demonstrated, to, be, involved, in, several, 'diseases,', such, as, 'cancer,', autoimmunity, and, other, 'pathogen-mediated', 'immune-regulated', diseases])]). relacion([sujeto(['Granulocyte', 'colony-stimulating', factor, '(', 'G-CSF)']), verbo([has]), complemento([been, shown, to, decrease, the, 'Th1/Th2', ratio, in, healthy, donors])]). relacion([sujeto(['The', mRNA, expression, of, 'IFN-γ,', 'IL-2,', 'IL-4,', 'IL-13,', and, 'T-box']), verbo([expressed]), complemento([in, 'T', cells, '(', 'T-bet)', and, 'GATA-binding', protein, 3, '(', 'GATA-3)', in, 'PBMCs', was, evaluated, by, reverse, transcription, polymerase, chain, reaction])]). relacion([sujeto(['As', the, concentration, of, 'G-CSF', 'increased,', 'Th1/Th2', '(', '[', 'IFN-γ+IL-2]/[IL-4+IL-13])', cytokine, ratios, and, 'T-bet/GATA-3', mRNA, ratios]), verbo([decreased]), complemento([in, a, 'concentration-dependent', manner])]). relacion([sujeto(['Th1', cells, and, 'Th2', cells, both]), verbo([expressed]), complemento(['G-CSFR'])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, 'G-CSF', could, decrease, the, 'Th1/Th2', ratio, in, the, context, of, 'ITP,', and, elucidate, the, direct, and, indirect, immunomodulatory, mechanisms, underlying, 'G-CSF', functions, in, 'Th1/Th2', 'cells,', thus, supporting, the, therapeutic, potential, of, 'G-CSF', in, the, treatment, of, patients, with, 'ITP'])]). relacion([sujeto(['Estrogen', is]), verbo([reported]), complemento([to, be, involved, in, thrombopoiesis, and, the, disruption, of, its, signaling, may, cause, myeloproliferative, 'disease,', yet, the, underlying, mechanisms, remain, largely, unknown])]). relacion([sujeto(['GATA-binding', factor, 1, '(', 'GATA1)', is, a, key, regulator, of, megakaryocyte, '(', 'MK)', differentiation, and, its, deficiency, will]), verbo([lead]), complemento([to, megakaryoblastic, leukemia])]). relacion([sujeto(['Here', we, show, that, estrogen, can, 'dose-dependently']), verbo([promote]), complemento(['MK', polyploidization, and, maturation, via, activation, of, estrogen, receptor, beta, '(', 'ERβ),', accompanied, by, a, significant, upregulation, of, 'GATA1'])]). relacion([sujeto(['Chromatin', immunoprecipitation, and, a, dual, luciferase, assay, demonstrate, that, 'ERβ', can, directly]), verbo([bind]), complemento([the, promoter, region, of, 'GATA1', and, activate, its, transcription])]). relacion([sujeto(['Steroid', receptor, coactivator, 3, '(', 'SRC3)', is]), verbo([involved]), complemento([in, 'ERβ-mediated', 'GATA1', transcription])]). relacion([sujeto(['The', deficiency, of, 'ERβ', or, 'SRC3,', similar, to, the, inhibition, of, 'GATA1,']), verbo([leads]), complemento([to, the, impediment, of, 'estrogen-induced', 'MK', polyploidization, and, platelet, production])]). relacion([sujeto(['Further', investigations]), verbo([reveal]), complemento([that, signal, transducer, and, activator, of, transcription, 1, signaling, pathway, downstream, of, 'GATA1', has, a, crucial, role, in, 'estrogen-induced', 'MK', 'polyploidization,', and, 'ERβ-mediated', 'GATA1', upregulation, subsequently, enhances, nuclear, factor, 'erythroid-derived', 2, 'expression,', thereby, promoting, proplatelet, formation, and, platelet, release])]). relacion([sujeto(['Our', study]), verbo([provides]), complemento([a, deep, insight, into, the, molecular, mechanisms, of, estrogen, signaling, in, regulating, thrombopoiesis, and, the, pathogenesis, of, 'ER', 'deficiency-related', leukemia])]). relacion([sujeto(['Sex', chromosome, evolution]), verbo([involves]), complemento([the, accumulation, of, repeat, sequences, such, as, multigenic, 'families,', noncoding, repetitive, 'DNA', '(', 'satellite,', 'minisatellite,', and, 'microsatellite),', and, mobile, elements, such, as, transposons, and, retrotransposons])]). relacion([sujeto(['The', '(', 'TAA)10', repeat, is, accumulated, in, the, entire, 'W', 'chromosome,', and, this, microsatellite, accumulation, is, probably]), verbo([involved]), complemento([in, the, sex, chromosome, differentiation, process, and, crossover, suppression, in, 'C'])]). relacion([sujeto(['Altered', progesterone, responsiveness]), verbo([leads]), complemento([to, female, infertility, and, 'cancer,', but, underlying, mechanisms, remain, unclear])]). relacion([sujeto(['Mice', with, 'uterine-specific', ablation, of, 'GATA']), verbo([binding]), complemento([protein, 2, '(', 'Gata2)', are, 'infertile,', showing, failures, in, embryo, 'implantation,', endometrial, 'decidualization,', and, uninhibited, estrogen, signaling])]). relacion([sujeto(['GATA2', not, only, occupies, at, and]), verbo([promotes]), complemento([expression, of, the, 'Pgr', gene, but, also, regulates, downstream, progesterone, responsive, genes, in, conjunction, with, the, 'PGR'])]). relacion([sujeto(['Additionally,', 'Gata2', knockout, 'uteri exhibit', abnormal, luminal, epithelia, with, ectopic, 'TRP63']), verbo([expressing]), complemento([squamous, cells, and, a, 'cancer-related', molecular, profile, in, a, 'progesterone-independent', manner])]). relacion([sujeto(['Lastly,', we]), verbo([found]), complemento([a, conserved, 'GATA2-PGR', regulatory, network, in, both, human, and, mice, based, on, gene, signature, and, path, analyses, using, gene, expression, profiles, of, human, endometrial, tissues])]). relacion([sujeto(['In', 'conclusion,', uterine, 'Gata2']), verbo([regulates]), complemento([a, key, regulatory, network, of, gene, expression, for, progesterone, signaling, at, the, early, pregnancy, stage])]). relacion([sujeto(['Although', the, importance, of, dendritic, cells]), verbo([has]), complemento([been, demonstrated, in, many, animal, 'models,', their, contribution, to, human, immunity, remains, relatively, unexplored, in, vivo])]). relacion([sujeto(['Given', their, central, role, in, 'infection,', 'autoimmunity,', and, 'malignancy,', dendritic, cell, deficiency, or, dysfunction, would, be, expected, to]), verbo([have]), complemento([clinical, consequences])]). relacion([sujeto(['Human', dendritic, cell, deficiency, 'disorders,', related, to, 'GATA']), verbo([binding]), complemento([protein, 2, '(', 'GATA2)', and, interferon, regulatory, factor, 8, '(', 'IRF8)', 'mutations,', have, highlighted, the, importance, of, dendritic, cells, and, monocytes, in, primary, immunodeficiency, diseases, and, begun, to, shed, light, on, their, nonredundant, roles, in, host, defense, and, immune, regulation, in, vivo])]). relacion([sujeto(['Notch', signaling, is]), verbo([involved]), complemento([in, the, early, process, of, differentiation, to, determine, the, fate, of, stem, cells])]). relacion([sujeto(['Flow', cytometric, analysis, revealed, that, 'CD29,', 'CD44', and, 'CD90', were, highly]), verbo([expressed]), complemento([on, the, surface, of, cells, in, their, fifth, 'passage,', whereas, detection, of, 'CD34,', 'CD45,', 'CD54', and, 'HLA‑DR', was, negative])]). relacion([sujeto(['Western', blotting, and, immunocytochemistry, demonstrated]), verbo([increased]), complemento([protein, expression, levels, of, 'α‑actin', and, cardiac, troponin, 'T', 'expression,', and, 'RT‑qPCR', revealed, increased, mRNA, expression, of, 'Notch1', early, in, the, process, of, differentiation, '(', days, 1, ',', 4, and, 7, ')', ',', and, increased, mRNA, expression, levels, of, the, transcription, factors, 'GATA', binding, 'protein‑4', and, 'NK2', homeobox, 5, at, day, 28, &, 'nbsp;day'])]). relacion([sujeto(['In', 'conclusion,', differentiation, of, hBMSCs, into, cardiomyocytes, was]), verbo([induced]), complemento(['in vitro', by, 5, &, #, 8209, ;, 'aza,', and, was, associated, with, upregulation, of, 'Notch1,', 'GATA', binding, 'protein‑4', and, 'Nkx2'])]). relacion([sujeto(['Recently,', interest, in, the, beneficial, role, of, probiotics, in, the, protection, and, management, of, allergic, diseases]), verbo([caused]), complemento([by, immune, disorders, has, been, increasing])]). relacion([sujeto(['This', study, investigated, the, inhibitory, effect, of, 'Lactobacillus', plantarum, 'L67', on]), verbo([induced]), complemento([allergic, inflammatory, response, in, bisphenol, 'A-treated', rat, basophilic, leukemia, 2, 'H3', '(', 'RBL-2H3)', cells, and, mouse, splenocytes])]). relacion([sujeto(['We', measured, the, ability, of, 'Lactobacillus', strains, to]), verbo([induce]), complemento([the, production, of, 'IL-12', and, 'IFN-', γ, in, cultured, splenocytes, by, 'ELISA'])]). relacion([sujeto(['Our', results, showed, that, 'L67', protein]), verbo([inhibited]), complemento([the, phosphorylation, of, 'ERK', and, p38, 'mitogen-activated', protein, kinase, through, the, transcriptional, activation, of, 'AP-1', in, bisphenol, 'A-treated', 'RBL-2H3', cells])]). relacion([sujeto(['During', differentiation, of, 'T', helper, 'cells,', the, expression, of, transcription, factor, 'GATA-3', was, significantly]), verbo([suppressed]), complemento([by, 'L67', protein, '(', 100, 'µg/mL)', 'treatment,', whereas, expression, of, transcription, factor, 'T-bet', was, increased])]). relacion([sujeto([plantarum, 'L67,', made, available, as, yogurt, starters, and, dietary, 'supplements,']), verbo([has]), complemento([the, potential, to, prevent, 'allergy-related', immune, disorders])]). relacion([sujeto(['Among', the, histological, subtypes, of, breast, 'cancer,', invasive, lobular, carcinomas]), verbo([have]), complemento([a, high, capacity, of, metastasis, to, uncommon, sites, including, the, stomach])]). relacion([sujeto(['Conversely,', there]), verbo([has]), complemento([not, been, sufficient, evidence, supporting, the, gastric, metastasis, of, invasive, ductal, carcinoma])]). relacion([sujeto(['Herein,', we]), verbo([report]), complemento([a, unique, case, of, metastatic, ductal, breast, carcinoma, mimicking, primary, linitis, plastica, in, a, male, 'patient,', particularly, focusing, on, the, clinical, and, pathological, features, of, presentation])]). relacion([sujeto(['Moreover,', we, propose, a, immunohistochemical, panel, of, selected, antibodies, including, those, for, cytokeratin, 20, ',', cytokeratin, 7, ',', estrogen, 'receptor,', progesterone, 'receptor,', 'E-cadherin,', gross, cystic, disease, fluid, protein, 15, ',', and, 'GATA']), verbo([binding]), complemento([protein, 3, for, an, accurate, differential, diagnosis])]). relacion([sujeto(['Accumulating', evidence]), verbo([reveals]), complemento([that, hormone, 'leptin,', mainly, produced, by, 'adipocyte,', plays, a, unique, role, in, promotion, of, liver, fibrosis])]). relacion([sujeto(['Hepatic', stellate, cell, '(', 'HSC)', activation, is, a, key, step, in, liver, fibrosis, and, 'peroxisome-proliferator']), verbo([activated]), complemento([receptor, γ, '(', 'PPARγ)', exerts, a, crucial, role, in, inhibition, of, 'HSC', activation])]). relacion([sujeto(['Our', previous, researches, demonstrated, that, leptin, reduced, 'PPARγ1', '(', a, major, subtype, of, 'PPARγ', in, 'HSCs)', expression, through, 'GATA']), verbo([binding]), complemento([protein, 2, '(', 'GATA2)', binding, to, a, site, around, -, 2323, in, 'PPARγ1', promoter])]). relacion([sujeto(['Results', demonstrate, that, leptin, significantly]), verbo([induces]), complemento(['GATA3', expression, in, 'HSCs', by, multiple, signalling, pathways, including, 'NADPH', oxidase, pathway])]). relacion([sujeto(['GATA3', can]), verbo([bind]), complemento([to, 'GATA2-binding', site, in, 'PPARγ1', promoter, and, interacts, with, 'GATA2,', contributing, to, leptin, inhibition, of, 'PPARγ1', expression, in, 'HSCs'])]). relacion([sujeto(['These', data, demonstrated, novel, molecular, events, for, leptin, inhibition, of, 'PPARγ1', expression, in, 'HSCs', and, thus, might]), verbo([have]), complemento([potential, implications, for, clarifying, the, detailed, mechanisms, underlying, liver, fibrosis, in, diseases, in, which, circulating, leptin, levels, are, elevated, such, as, 'non-alcoholic', steatohepatitis, in, obese, patients])]). relacion([sujeto(['Memory', 'T', cells, are, thought, to, be, of, a, primarily, 'T', helper, 1, 'type,', but, both, 'T', helper, 1, and, 'T', helper, 2, memory, cells]), verbo([have]), complemento([been, 'described,', and, heightened, 'T', helper, 2, /, lessened, 'T', helper, 1, responses, have, been, associated, with, increased, 'RV-induced', asthma, exacerbation, severity])]). relacion([sujeto(['Using', flow, cytometry, we, showed, that, 'Tbet', deficient, mice, lacked, the, 'T', helper, 1, response, of, wild, type, mice, and, instead, developed, mixed, 'T', helper, 2, /, 'T', helper, 17, responses, to, 'RV', 'infection,', evidenced, by]), verbo([increased]), complemento([numbers, of, 'GATA', binding, protein, 3, '(', 'GATA-3)', and, 'RAR-related', orphan, receptor, gamma, t, '(', 'RORγt),', and, 'interleukin-13', and, 'interleukin-17A', expressing, 'CD4+', 'T', cells, in, the, lung])]). relacion([sujeto(['Forkhead', box, 'P3', '(', 'FOXP3)', and, 'interleukin-10']), verbo([expressing]), complemento(['T', cell, numbers, were, unaffected])]). relacion([sujeto(['Tbet', deficient, mice, exhibited, pronounced, airways, eosinophilia, and, mucus, production, in, response, to, 'RV', infection, 'that,', by, utilising, a, 'CD4+', cell, depleting, 'antibody,', were]), verbo([found]), complemento([to, be, 'T', helper, cell, dependent])]). relacion([sujeto(['RV', induction, of, 'T', helper, 2, and, 'T', helper, 17, responses, may, therefore]), verbo([have]), complemento([an, important, role, in, directly, driving, features, of, allergic, airways, disease, such, as, eosinophilia, and, mucus, hypersecretion, during, asthma, exacerbations])]). relacion([sujeto(['Recurrent', 'BRAF', 'V600E', mutation]), verbo([has]), complemento([been, reported, in, 'LCH'])]). relacion([sujeto(['We', then, assessed, the, tumor, immune, microenvironment, status, in, 'LCH,', and]), verbo([found]), complemento([that, the, 'GATA', binding, protein, 3, '(', 'GATA3)(+)/T-bet(+)', ratio, could, distinguish, between, clinical, 'multi-system/single-system', '(', 'SS)', multifocal, and, 'SS', unifocal, 'LCH'])]). relacion([sujeto(['Notably,', we]), verbo([found]), complemento([that, 'BRAF', 'V600E', mutation, is, significantly, correlated, with, increased, programmed, cell, death, 1, ligand, 1, '(', 'PDL1)', expression, and, forkhead, box, protein, 3, '(', 'FOXP3)(+)', regulatory, 'T', cells, '(', p, &, 'lt;', 0.001, ',', 0.009, ',', 'respectively)'])]). relacion([sujeto(['Our', findings, may]), verbo([provide]), complemento([a, rationale, for, combining, immunotherapy, and, 'BRAF-targeted', therapy, for, treating, patients, with, 'BRAF', 'V600E', mutant, 'LCH'])]). relacion([sujeto(['Cell', proliferation, was, assessed, using, a, cell, counting, kit, and, proliferating, cell]), verbo([nuclear]), complemento([antigen, expression, was, determined, by, western, blotting])]). relacion([sujeto(['Silencing', of, 'TBX20', in, 'H9c2', and, 'HEK293', cells, significantly]), verbo([inhibited]), complemento([cell, 'proliferation,', induced, cell, apoptosis, and, led, to, 'G2/M', cell, cycle, arrest])]). relacion([sujeto(['A', reduction, in, cyclin, 'B1', mRNA, levels, and, an]), verbo([increase]), complemento([in, 'cyclin‑dependent', kinase, 'inhibitor 1B', mRNA, levels, was, 'observed,', which, indicated, that, cells, were, arrested, in, 'G2', phase])]). relacion([sujeto(['Concurrently,', the, mRNA, levels, of, 'GATA']), verbo([binding]), complemento(['protein 4', were, increased, in, both, cell, 'lines,', which, may, provide, an, explanation, for, the, abnormal, cardiac, hypertrophy, observed, in, patients, with, congenital, heart, disease])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, 'TBX20', is, required, for, heart, 'morphogenesis,', and, inhibition, of, 'TBX20', expression, may, lead, to, the, suppression, of, cell, proliferation, and, cell, cycle, arrest])]). relacion([sujeto(['GATA']), verbo([binding]), complemento([protein, 3, '(', 'GATA-3)', was, inserted, as, control])]). relacion([sujeto(['Subunit', 'HdrB', of, the, 'Methanothermobacter', marburgensis, 'HdrABC', holoenzyme, contains, two, 'cysteine-rich', sequence, motifs, '(', 'CX31-39CCX35-36CXXC),', designated, as, 'CCG', domain, in, the, 'Pfam', database, and]), verbo([conserved]), complemento([in, many, proteins])]). relacion([sujeto(['Here', we, present, experimental, evidence, that, the, 'C-terminal', 'CCG', domain, of, 'HdrB']), verbo([binds]), complemento([this, unusual, '[', 4, 'Fe-4S]', cluster])]). relacion([sujeto(['CoM-33SH', resulted, in, a, broadening, of, the, 'EPR', 'signal,', and, upon, addition, of, 'CoM-SH', the, midpoint, potential, of, the, cluster, was, shifted, to, values, observed, for, 'CoM-HDR,', both, indicating]), verbo([binding]), complemento([of, 'CoM-SH', to, the, cluster])]). relacion([sujeto(['The', 'N-terminal', 'CCG', domain, is]), verbo([suggested]), complemento([to, provide, ligands, to, the, 'Zn', site])]). relacion([sujeto(['Development', of, engineered, 'site-specific', endonucleases, like, zinc, finger, nucleases, '(', 'ZFNs),', transcription, 'activator-like', effector, nucleases, '(', 'TALENs),', and, 'CRISPR/Cas9']), verbo([has]), complemento([been, revolutionizing, genetic, approaches, in, biomedical, research, fields])]). relacion([sujeto(['These', new, tools]), verbo([have]), complemento([opened, opportunities, to, carry, out, targeted, genome, editing, in, mouse, zygotes, without, the, need, for, manipulating, embryonic, stem, 'cells,', which, have, a, higher, technical, burden, and, many, constraints, in, strain, availability])]). relacion([sujeto(['This', new, approach, saves, time, and, costs]), verbo([associated]), complemento([with, generation, and, backcrossing, of, genetically, modified, animals, and, will, facilitate, their, use, in, various, cancer, research, fields])]). relacion([sujeto(['Medical', records, of, eight, patients, from, five, unrelated, families, exhibiting, 'GATA-3', mutations, were, reviewed, 'retrospectively,', in, conjunction, with, all, previously]), verbo([reported]), complemento([cases])]). relacion([sujeto(['Sensorineural', deafness, was, consistently, 'diagnosed,', ranging, from, clinical, hearing]), verbo([loss]), complemento([since, infancy, in, seven, patients, to, deafness, detected, only, by, audiometry, in, adulthood, in, one, single, patient])]). relacion([sujeto(['Interestingly,', phenotype, severity, differed, significantly, between, a, mother, and]), verbo([son]), complemento([within, one, family])]). relacion([sujeto(['C339W)]', or, the]), verbo([conserved]), complemento([linker, region, '[', c])]). relacion([sujeto(['Review', of, 115, previously]), verbo([reported]), complemento([cases, of, 'GATA-3', mutations, showed, hypoparathyroidism, and, deafness, in, 95, '%', of, 'patients,', and, renal, abnormalities, in, only, 60, '%'])]). relacion([sujeto(['Diagnosis', of, 'HDR', should, be, considered, in, any, patient, with, hypoparathyroidism, and, 'deafness,', whether]), verbo([associated]), complemento([with, renal, abnormalities, or, not])]). relacion([sujeto(['Recent', advances, in, the]), verbo([targeted]), complemento([genome, engineering, enable, molecular, biologists, to, generate, sequence, specific, modifications, with, greater, efficiency, and, higher, specificity, in, complex, eukaryotic, genomes])]). relacion([sujeto(['Programmable', 'site-specific', 'DNA', cleavage, reagents, and, cellular, 'DNA', repair, mechanisms]), verbo([have]), complemento([made, this, possible])]). relacion([sujeto(['These', reagents]), verbo([have]), complemento([become, powerful, tools, for, delivering, a, 'site-specific', genomic, 'double-strand', break, '(', 'DSB)', at, the, desired, chromosomal, 'locus,', which, produces, sequence, alterations, through, 'error-prone', 'non-homologous', end, joining, '(', 'NHEJ)', resulting, in, gene, 'inactivations/knockouts'])]). relacion([sujeto(['Alternatively,', the, 'DSB', can, be, repaired, through, 'homology-directed', repair, '(', 'HDR)', using, a, donor, 'DNA', 'template,', which]), verbo([leads]), complemento([to, the, introduction, of, desired, sequence, modifications, at, the, predetermined, site])]). relacion([sujeto(['Here,', we, summarize, the, role, of, three, classes, of, 'nucleases;', zinc, finger, nucleases, '(', 'ZFNs),', transcription, activator, like, effector, nucleases, '(', 'TALENs),', and, clustered, regularly, interspaced, palindromic, repeats, '(', 'CRISPR)/CRISPR']), verbo([associated]), complemento([protein, 9, '(', 'Cas9)', system, in, achieving, targeted, genome, modifications])]). relacion([sujeto(['Genome-editing', of, human, pluripotent, stem, cells, '(', 'hPSCs)']), verbo([provides]), complemento([a, genetically, controlled, and, clinically, relevant, platform, from, which, to, understand, human, development, and, investigate, the, pathophysiology, of, disease])]). relacion([sujeto(['All', of, these, nucleases, function, by, introducing, a, double, stranded, 'DNA', break, at, a, specified, 'site,', thereby]), verbo([promoting]), complemento([precise, gene, editing, at, a, genomic, locus])]). relacion([sujeto(['Mechanically', separating, hPSC, colonies, and, confirming, proper, integration, at, the]), verbo([target]), complemento([site, through, genotyping, allows, for, the, isolation, of, correctly, targeted, and, genetically, homogeneous, cell, lines])]). relacion([sujeto(['Importantly,', 'knock-in', in, several, 'non-rodent', species]), verbo([has]), complemento([been, finally, achieved, thanks, to, these, customizable, 'nucleases;', yet, the, rates, remain, to, be, further, improved])]). relacion([sujeto(['We', hypothesize, that]), verbo([inhibiting]), complemento(['non-homologous', end, joining, '(', 'NHEJ)', or, enhancing, 'homology-directed', repair, '(', 'HDR)', will, improve, the, 'nuclease-mediated', 'knock-in', efficiency])]). relacion([sujeto(['Here', we, show, that, the, in, vitro, application, of, an, 'HDR', 'enhancer,', 'RS-1,']), verbo([increases]), complemento([the, 'knock-in', efficiency, by, 'two-', to, 'five-fold', at, different, 'loci,', whereas, 'NHEJ', inhibitor, 'SCR7', has, minimal, effects])]). relacion([sujeto(['We', then, apply, 'RS-1', for, animal, production, and]), verbo([have]), complemento([achieved, multifold, improvement, on, the, 'knock-in', rates, as, well])]). relacion([sujeto(['Over', recent, 'years,', genome, editing, approaches]), verbo([have]), complemento([become, increasingly, used, as, an, efficient, and, sophisticated, approach, to, precisely, engineer, the, zebrafish, 'genome,', which, has, further, enhanced, the, utility, of, this, organism])]). relacion([sujeto(['This', review]), verbo([provides]), complemento([a, practical, overview, of, genome, editing, and, its, application, in, zebrafish, 'research,', including, alternate, strategies, for, introducing, and, screening, for, specific, genetic, changes])]). relacion([sujeto(['Here,', we]), verbo([report]), complemento([the, 'HDR-mediated', gene, exchange, of, expression, cassettes, in, tobacco, 'BY-2', cells, using, a, designed, zinc, finger, nuclease, '(', 'ZFN)'])]). relacion([sujeto(['The']), verbo([target]), complemento([contained, a, 7, -, kb, fragment, flanked, by, two, 'ZFN', cutting, sites])]). relacion([sujeto(['That', fragment, was, replaced, with, a, 4, -, kb, donor, 'cassette,', which, integrates, gene, markers, for, selection, '(', kanamycin, 'resistance)', and, for, scoring]), verbo([targeting]), complemento(['(', red, fluorescent, 'protein,', 'RFP)'])]). relacion([sujeto(['Our', results, demonstrate, that, 'ZFN-based', 'HDR', can, be, used, for, high, 'frequency,', 'precise,']), verbo([targeted]), complemento([exchange, of, fragments, of, sizes, that, are, commercially, relevant, in, plants])]). relacion([sujeto(['Targeted', 'genome-editing', technology, using, designed, nucleases]), verbo([has]), complemento([been, evolving, 'rapidly,', and, its, applications, are, widely, expanding, in, 'research,', medicine, and, biotechnology])]). relacion([sujeto(['In', 'addition,', designed, 'nickase-induced', generation, of, 'single-strand', breaks, can, also]), verbo([lead]), complemento([to, precise, genome, editing, through, 'HDR,', albeit, at, relatively, lower, efficiencies, than, that, induced, by, nucleases])]). relacion([sujeto(['Three', kinds, of, designed, nucleases]), verbo([have]), complemento([been, used, for, targeted, 'DSB', 'formation:', 'zinc-finger', 'nucleases,', transcription, 'activator-like', effector, 'nucleases,', and, 'RNA-guided', engineered, nucleases, derived, from, the, bacterial, clustered, regularly, interspaced, short, palindromic, repeat, '(', 'CRISPR)-Cas', '(', 'CRISPR-associated)', system])]). relacion([sujeto(['A', growing, number, of, researchers, are, using, 'genome-editing', 'technologies,', which]), verbo([have]), complemento([become, more, accessible, and, affordable, since, the, discovery, and, adaptation, of, 'CRISPR-Cas9'])]). relacion([sujeto(['Genes']), verbo([associated]), complemento([with, hereditary, breast, and, ovarian, cancer, '(', 'HBOC)', are, often, sequenced, in, search, of, mutations, that, are, predictive, of, susceptibility, to, these, cancer, 'types,', but, the, sequence, results, are, frequently, ambiguous, because, of, the, detection, of, missense, substitutions, for, which, the, clinical, impact, is, unknown])]). relacion([sujeto(['Like', 'BRCA1,', it, is]), verbo([required]), complemento([for, 'homology-directed', 'DNA', repair, '(', 'HDR)'])]). relacion([sujeto(['In', the, 'BARD1', 'RING', 'domain,', critical, residues, mapped, to, the, 'zinc-coordinating', amino, acids, and, to, the, 'BRCA1-BARD1']), verbo([binding]), complemento(['interface,', highlighting, the, importance, of, interaction, between, 'BRCA1', and, 'BARD1', for, 'HDR', activity])]). relacion([sujeto(['Transcription', 'activator-like', effector, nucleases, open, up, new, opportunities, for]), verbo([targeted]), complemento([mutagenesis, in, eukaryotic, genomes])]). relacion([sujeto(['Similar', to, 'zinc-finger', 'nucleases,', 'sequence-specific', 'DNA-binding', domains, can, be, fused, with, effector, domains, like, the, nucleolytically, active, part, of, 'FokI', to]), verbo([induce]), complemento(['double-strand', breaks, and, thereby, modify, the, host, genome, on, a, predefined, target, site, via, nonhomologous, end, joining])]). relacion([sujeto(['More', sophisticated, applications, of, programmable, endonucleases]), verbo([involve]), complemento([the, use, of, a, 'DNA', repair, template, facilitating, 'homology-directed', repair, '(', 'HDR)', so, as, to, create, predefined, rather, than, random, 'DNA', sequence, modifications])]). relacion([sujeto(['The', aim, of, this, study, was, to, demonstrate, the, feasibility, of, editing, the, barley, genome, by, precisely, modifying, a, defined]), verbo([target]), complemento(['DNA', sequence, resulting, in, a, predicted, alteration, of, gene, function])]). relacion([sujeto(['We', used, 'gfp-specific', transcription, 'activator-like', effector, nucleases, along, with, a, repair, template, 'that,', via, 'HDR,', facilitates, conversion, of, gfp, into, 'yfp,', which, is]), verbo([associated]), complemento([with, a, single, amino, acid, exchange, in, the, gene, product])]). relacion([sujeto(['Homozygous', 32, -, bp, deletion, of, the, chemokine, receptor, 5, gene, '(', 'CCR5)', is]), verbo([associated]), complemento([with, resistance, to, human, immunodeficiency, virus, '(', 'HIV)', 'infection,', while, heterozygosity, delays, 'HIV', progression])]). relacion([sujeto(['Bone', marrow, transplantation, '(', 'BMT)', from, a, 32, /, 32, donor]), verbo([has]), complemento([been, shown, to, cure, an, 'HIV-infected', patient])]). relacion([sujeto(['However,', the, rarity, of, this, mutation, and, the, safety, risks]), verbo([associated]), complemento([with, current, 'BMT', protocols, are, the, major, obstacles, to, this, treatment])]). relacion([sujeto(['Zinc', finger, nuclease, '(', 'ZFN)']), verbo([targeting]), complemento([is, a, powerful, method, for, achieving, genomic, disruption, at, specific, 'DNA', sites, of, interest])]). relacion([sujeto(['We', here]), verbo([reported]), complemento([the, novel, approach, on, generation, of, patients, own, 'CD34', cells, from, high, fidelity, 'ZFN-mediated', 'HDR', 'MSC', clones])]). relacion([sujeto(['Methods', to, introduce]), verbo([targeted]), complemento(['double-strand', breaks, '(', 'DSBs)', into, 'DNA', enable, precise, genome, editing, by, increasing, the, rate, at, which, externally, supplied, 'DNA', fragments, are, incorporated, into, the, genome, through, homologous, recombination])]). relacion([sujeto(['To']), verbo([promote]), complemento(['HDR', at, the, expense, of, 'NHEJ,', we, targeted, 'DNA', ligase, 'IV,', a, key, enzyme, in, the, 'NHEJ', 'pathway,', using, the, inhibitor, 'Scr7'])]). relacion([sujeto(['Scr7', treatment]), verbo([increased]), complemento([the, efficiency, of, 'HDR-mediated', genome, 'editing,', using, 'Cas9', in, mammalian, cell, lines, and, in, mice, for, all, four, genes, 'examined,', up, to, 19, -, fold])]). relacion([sujeto(['This', approach, should, be, applicable, to, other, customizable, 'endonucleases,', such, as, zinc, finger, nucleases, and, transcription, 'activator-like', effector, 'nucleases,', and, to, nonmammalian, cells, with, sufficiently]), verbo([conserved]), complemento([mechanisms, of, 'NHEJ', and, 'HDR'])]). relacion([sujeto(['The', ability, to, create, 'DNA', 'double-strand', breaks, '(', 'DSBs)', at, specified, genomic, 'locations,', which, then]), verbo([stimulate]), complemento([the, 'cell\'s', naturally, occurring, 'DNA', repair, 'processes,', has, introduced, intriguing, possibilities, for, genetic, modification])]). relacion([sujeto(['Zinc', finger, nucleases, '(', 'ZFNs)', are, designed, restriction, enzymes, consisting, of, a, nonspecific, cleavage, domain, fused, to, 'sequence-specific', 'DNA']), verbo([binding]), complemento([domains])]). relacion([sujeto(['Similarly,', specific, 'DNA', sequence, modifications, can, be, made, by]), verbo([providing]), complemento([donor, 'DNA', templates, homologous, to, sequences, flanking, the, cleavage, site, via, 'homology-directed', repair, '(', 'HDR)'])]). relacion([sujeto(['Genome', editing, can, be, used, to]), verbo([enhance]), complemento([our, basic, understanding, of, plant, gene, function, as, well, as, modify, and, improve, crop, plants])]). relacion([sujeto(['Starting', with, skin, fibroblasts, from, patients, diagnosed, with, cystic, 'fibrosis,', we, derived, and, characterized]), verbo([induced]), complemento([pluripotent, stem, cell, '(', 'iPSC)', lines])]). relacion([sujeto(['We', then, utilized, 'zinc-finger', nucleases, '(', 'ZFNs),', designed, to]), verbo([target]), complemento([the, endogenous, 'CFTR', 'gene,', to, mediate, correction, of, the, inherited, genetic, mutation, in, these, 'patient-derived', lines, via, 'homology-directed', repair, '(', 'HDR)'])]). relacion([sujeto(['We', observed, an, exquisitely, 'sensitive,', 'homology-dependent', preference, for]), verbo([targeting]), complemento([one, 'CFTR', allele, versus, the, other])]). relacion([sujeto(['The', corrected, cystic, fibrosis, 'iPSCs,', when]), verbo([induced]), complemento([to, differentiate, 'in vitro,', expressed, the, corrected, 'CFTR', 'gene;', 'importantly,', 'CFTR', correction, resulted, in, restored, expression, of, the, mature, 'CFTR', glycoprotein, and, restoration, of, 'CFTR', chloride, channel, function, in, 'iPSC-derived', epithelial, cells])]). relacion([sujeto(['To', correct, a, 'DNA', mutation, in, the, human, genome, for, gene, 'therapy,', 'homology-directed', repair, '(', 'HDR)', needs, to, be, specific, and]), verbo([have]), complemento([the, lowest, 'off-target', effects, to, protect, the, human, genome, from, deleterious, mutations])]). relacion([sujeto(['Zinc', finger, 'nucleases,', transcription, 'activator-like', effector, nuclease, '(', 'TALEN)', and, 'CRISPR-CAS9', systems]), verbo([have]), complemento([been, engineered, and, used, extensively, to, recognize, and, modify, specific, 'DNA', sequences])]). relacion([sujeto(['Although', 'TALEN', and, 'CRISPR/CAS9', could]), verbo([induce]), complemento([high, levels, of, 'HDR', in, human, 'cells,', their, genotoxicity, was, significantly, higher])]). relacion([sujeto(['Here,', we]), verbo([report]), complemento([the, creation, of, a, monomeric, endonuclease, that, can, recognize, at, least, 33, bp, by, fusing, the, 'DNA-recognizing', domain, of, 'TALEN', '(', 'TALE)', to, a, 're-engineered', homing, endonuclease, 'I-SceI'])]). relacion([sujeto(['After', sequentially, 're-engineering', 'I-SceI', to]), verbo([recognize]), complemento([18, bp, of, the, human, 'β-globin', 'sequence,', the, 're-engineered', 'I-SceI', induced, 'HDR', in, human, cells])]). relacion([sujeto(['When', the, 're-engineered', 'I-SceI', was, fused, to, 'TALE', '(', 'TALE-ISVB2),', the, chimeric, endonuclease]), verbo([induced]), complemento([the, same, 'HDR', rate, at, the, human, 'β-globin', gene, locus, as, that, induced, by, 'TALEN,', but, significantly, reduced, genotoxicity])]). relacion([sujeto(['We', further, demonstrated, that, 'TALE-ISVB2', specifically]), verbo([targeted]), complemento([at, the, 'β-globin', sequence, in, human, hematopoietic, stem, cells])]). relacion([sujeto(['Therefore,', this, monomeric, endonuclease]), verbo([has]), complemento([the, potential, to, be, used, in, therapeutic, gene, targeting, in, human, cells])]). relacion([sujeto(['Gene', editing, using, engineered, 'endonucleases,', such, as, zinc, finger, nucleases, '(', 'ZFNs),', transcription, 'activator-like', effector, nucleases, '(', 'TALENs),', and, clustered, regularly, interspaced, short, palindromic, repeats, '(', 'CRISPR)/Cas9', 'nucleases,']), verbo([requires]), complemento([the, creation, of, a, 'targeted,', chromosomal, 'DNA', 'double-stranded', break, '(', 'DSB)'])]). relacion([sujeto(['NHEJ', is, an, 'error-prone', repair, process, that, can, result, in, a, wide, range, of, 'end-joining', events, that]), verbo([leads]), complemento([to, somewhat, random, mutations, at, the, site, of, 'DSB'])]). relacion([sujeto(['Traditional', gene, editing, via, 'HDR']), verbo([has]), complemento([relied, on, the, 'co-delivery', of, a, 'targeted,', engineered, endonuclease, and, a, circular, plasmid, donor, construct])]). relacion([sujeto(['More', 'recently,', it]), verbo([has]), complemento([been, shown, that, 'single-stranded', oligodeoxynucleotides, '(', 'ssODNs)', can, also, serve, as, 'DNA', donors, and, thus, obviate, the, more, laborious, and, 'time-consuming', plasmid, vector, construction, process])]). relacion([sujeto(['The', ability, to, edit, the, genome, of, cell, lines]), verbo([has]), complemento([provided, valuable, insights, into, biological, processes, and, the, contribution, of, specific, mutations, to, disease, biology])]). relacion([sujeto(['Adeno-Associated', 'Virus', '(', 'AAV)', utilizes, homologous, recombination, to, generate, precise, and, predictable, genetic, modifications, directly, at, the]), verbo([target]), complemento([locus])]). relacion([sujeto(['AAV']), verbo([has]), complemento([been, used, to, create, over, 500, human, isogenic, cell, lines, comprising, a, wide, range, of, genetic, alterations, from, gene, 'knockouts,', insertions, of, point, 'mutations,', 'indels,', epitope, 'tags,', and, reporter, genes])]). relacion([sujeto(['Here', we, describe, the, generation, and, use, of, 'AAV', gene]), verbo([targeting]), complemento([vectors, and, viruses, to, create, targeted, isogenic, cell, lines])]). relacion([sujeto(['CRISPR/Cas9', technology, is, a, highly, promising, genome, editing, tool, in, the, 'mouse,', potentially, overcoming, the, costs, and, time]), verbo([required]), complemento([for, more, traditional, gene, targeting, methods, in, embryonic, stem, '(', 'ES)', cells])]). relacion([sujeto(['Recently,', compared, to, the, wildtype, 'nuclease,', paired, 'Cas9', nickase, '(', 'Cas9n)', combined, with, single, guide, 'RNA', '(', 'sgRNA)', molecules]), verbo([has]), complemento([been, found, to, enhance, the, specificity, of, genome, editing, while, reducing, 'off-target', effects])]). relacion([sujeto(['Paired', 'Cas9n']), verbo([has]), complemento([been, shown, to, be, as, efficient, as, 'Cas9', for, generating, insertion, and, deletion, '(', 'indel)', mutations, by, 'non-homologous', end, joining, and, targeted, deletion, in, the, genome])]). relacion([sujeto(['However,', an, efficient, and, reliable, approach, to, the, insertion, of, loxP, sites, flanking, critical, 'exon(s)', to, create, a, conditional, allele, of, a]), verbo([target]), complemento([gene, remains, an, elusive, goal])]). relacion([sujeto(['After', surgical, 'transfer,', one, 'F0', mouse]), verbo([expressing]), complemento([a, conditional, allele, was, produced, '(', at, a, frequency, of, '∼8%', of, live, pups, 'born)'])]). relacion([sujeto(['This', study, indicates, that, conditional]), verbo([targeting]), complemento([can, be, accomplished, effectively, using, paired, 'Cas9n', and, a, single, 'DNA', template])]). relacion([sujeto(['To']), verbo([report]), complemento([a, rare, case, of, 'vitreo-retinal', metastasis, from, urothelial, carcinoma, of, the, bladder])]). relacion([sujeto(['This', is, an, 'open-access', article, distributed, under, the, terms, of, the, 'Creative', 'Commons', 'Attribution-Non', 'Commercial-No', 'Derivatives', 'License', 4.0, '(', 'CCBY-NC-ND),', where, it, is, permissible, to, download, and, share, the, work]), verbo([provided]), complemento([it, is, properly, cited])]). relacion([sujeto(['They', typically]), verbo([express]), complemento([oestrogen, receptor, '(', 'ER),', are, 'HER2-negative', and, of, luminal, subtype])]). relacion([sujeto(['Eighteen', 'ER+/HER2-', 'NBCs,', defined, as, harbouring, &, 'gt;50%', of, tumour, cells]), verbo([expressing]), complemento([chromogranin, 'A', 'and/or', 'synaptophysin,', and, matched, normal, tissue, were, microdissected, and, subjected, to, massively, parallel, sequencing, targeting, all, exons, of, 254, genes, most, frequently, mutated, in, breast, cancer, 'and/or', related, to, 'DNA', repair])]). relacion([sujeto(['NBCs', were]), verbo([found]), complemento([to, harbour, a, median, of, 4.5, '(', range, 1, -, 11, ')', somatic, 'mutations,', similar, to, that, of, luminal, 'B', breast, cancers, '(', median, =, 3, ',', range, 0, -, 17, ')', but, significantly, higher, than, that, of, luminal, 'A', breast, cancers, '(', median, =, 3, ',', range, 0, -, 18, ',', p, =, 0.02, ')'])]). relacion([sujeto(['Discrete', bladder, cancer, molecular, subtypes, exhibit, differential, clinical, aggressiveness, and, therapeutic, 'response,', which, may]), verbo([have]), complemento([significant, implications, for, identifying, novel, treatments, for, this, common, malignancy])]). relacion([sujeto(['Using', the, molecular, subtype, 'assignments,', and, our, own, 'RNA-seq', 'analysis,', we]), verbo([found]), complemento([overexpression, of, 'GATA3', and, 'FOXA1', cooperate, with, 'PPARɣ', activation, to, drive, transdifferentiation, of, a, basal, bladder, cancer, cells, to, a, luminial, phenotype])]). relacion([sujeto(['We', established, an, experimental, system, that, can]), verbo([induce]), complemento(['p53-dependent', apoptosis, by, doxycycline, treatment, to, analyze, characteristics, of, the, 'apoptosis-resistant', cancer, cell, subpopulation, in, the, human, breast, cancer, cell, line, 'HCC1937'])]). relacion([sujeto(['After', doxycycline, 'treatment,', the, number, of, viable, cells, was, gradually]), verbo([decreased]), complemento([over, seven, days, in, a, 'time-dependent', manner, due, to, 'p53-induced', 'apoptosis;', 'however,', the, number, of, 'smaller-sized', 'ALDH1A3(+)', cells, assessed, by, immunostaining, increased, sharply, after, 1, day, of, doxycycline, 'treatment,', suggesting, their, 'apoptosis-resistant', nature])]). relacion([sujeto(['Molecular', analysis, of, 'Th2', cell, differentiation, and, maintenance, of, function]), verbo([has]), complemento([led, to, recent, discoveries, that, have, refined, our, understanding, of, 'Th2', cell, biology])]). relacion([sujeto(['Epigenetic', regulation, of, 'Gata3', expression, by, chromatin, remodeling, complexes, such, as, 'Polycomb', and, 'Trithorax', is, crucial, for]), verbo([maintaining]), complemento(['Th2', cell, identity])]). relacion([sujeto(['In', the, context, of, allergic, 'diseases,', 'memory-type', pathogenic, 'Th2', cells]), verbo([have]), complemento([been, identified, in, both, mice, and, humans])]). relacion([sujeto(['To', better, understand, these, 'disease-driving', cell, 'populations,', we]), verbo([have]), complemento([developed, a, model, called, the, pathogenic, 'Th', population, disease, induction, model])]). relacion([sujeto(['We', examined, paired]), verbo([targeted]), complemento([next, generation, sequencing, genotypes, from, 155, paraffin, tumors, corresponding, to, 76, 'BBC', patients, '(', 75, women, and, one, 'man;', 52, concurrent, and, 24, 'metachronous),', for, coding, mutations, '(', amino, acid, 'changing,', minor, allele, frequency, &, 'lt;0'])]). relacion([sujeto(['Phe341Val,', first]), verbo([report]), complemento([in, the, 'germline)'])]). relacion([sujeto(['A', considerable, minority, 'though,']), verbo([retains]), complemento([clonal, origin, and, may, be, regarded, as, a, distinct, group, for, therapeutic, interventions, among, concurrent, 'BBC'])]). relacion([sujeto(['Comprehensive', molecular, profiling]), verbo([has]), complemento([the, potential, to, contribute, to, diagnostic, categorization, 'and,', most, 'importantly,', guide, 'CUP', therapy, through, identification, of, actionable, lesions])]). relacion([sujeto(['We', here]), verbo([report]), complemento([the, case, of, an, 'advanced-stage', malignancy, initially, mimicking, poorly, differentiated, 'soft-tissue', sarcoma, that, did, not, respond, to, multiagent, chemotherapy])]). relacion([sujeto(['Integrated', analysis, of, molecular, data, and, histopathology]), verbo([provided]), complemento([a, rationale, for, immune, checkpoint, inhibitor, '(', 'ICI)', therapy, with, 'pembrolizumab,', which, resulted, in, rapid, clinical, improvement, and, a, lasting, partial, remission])]). relacion([sujeto(['We', analyzed, 157, 'TNBC', samples, from, 'The', 'Cancer', 'Genome', 'Atlas,']), verbo([revealed]), complemento(['PDL1', copy, number, gains, coinciding, with, excessive, 'PDL1', mRNA, expression, in, 24, '%', of, cases])]). relacion([sujeto(['Collectively,', these, results, illustrate, the, impact, of, multidimensional, tumor, profiling, in, cases, with, nondescript, histology, and, 'immunophenotype,', show, the, predictive, potential, of, 'PDL1', amplification, for, immune, checkpoint, inhibitors, '(', 'ICIs),', and]), verbo([suggest]), complemento([a, targeted, therapeutic, strategy, in, 'Chromosome', 9, p24])]). relacion([sujeto(['Although', previous, studies]), verbo([suggested]), complemento([that, 'microRNA-506-3p', '(', 'miR-506-3p)', was, frequently, 'downregulated,', and, functioned, as, a, tumor, suppressor, in, several, 'cancers,', the, biological, role, and, intrinsic, regulatory, mechanisms, of, 'miR-506-3p', in, 'non-small', cell, lung, cancer, '(', 'NSCLC)', remain, elusive])]). relacion([sujeto(['The', present, study]), verbo([found]), complemento(['miR-506-3p', expression, was, downregulated, in, advanced, 'NSCLC', tissues, and, cell, lines])]). relacion([sujeto(['In', 'addition,', we, also]), verbo([found]), complemento([patients, with, lower, expression, of, 'miR-506-3p', had, a, poor, prognosis, than, those, patients, with, higher, expression, of, 'miR-506-3p'])]). relacion([sujeto(['Function', studies, demonstrated, that, aberrant, 'miR-506-3p', expression]), verbo([modulates]), complemento([tumor, cell, 'growth,', cell, 'mobility,', cell, migration, and, invasion, in, vitro, and, in, vivo])]). relacion([sujeto(['Mechanistic', investigations, manifested, that, 'coactosin-like', protein, 1, '(', 'COTL1)', was, a, direct, downstream]), verbo([target]), complemento([of, 'miR-506-3p'])]). relacion([sujeto(['Knockdown', of, 'COTL1', mimicked, the, 'tumor-suppressive', effects, of, 'miR-506-3p', overexpression, in, 'A549', 'cells,', whereas, 'COTL1', overexpression]), verbo([enhanced]), complemento([the, tumorigenic, function, in, 'HCC827', cells])]). relacion([sujeto(['Importantly,', we, also]), verbo([found]), complemento(['GATA3', transcriptionally, actives, 'miR-506-3p', 'expression,', and, the, long, 'non-coding', 'RNA', urothelial, 'carcinoma-associated', 1, '(', 'UCA1)', exerts, oncogenic, function, in, 'NSCLC', by, competitively, '\'', 'sponging\'', 'miRNA-506'])]). relacion([sujeto(['Together,', our, combined, results, elucidated, genetic, and, epigenetic, silencing, of, 'miR-506-3p']), verbo([enhances]), complemento(['COTL1', oncogene, expression, to, foster, 'NSCLC', progression])]). relacion([sujeto(['Deletion', of, 'RHS6']), verbo([caused]), complemento([a, dramatic, resistance, to, allergic, airway, inflammation])]). relacion([sujeto(['RHS6']), verbo([recruited]), complemento([transcription, factors, 'GATA3,', 'SATB1,', and, 'IRF4,', which, play, important, roles, in, expression, of, all, three, 'Th2', cytokine, genes])]). relacion([sujeto(['RHS6', deficiency]), verbo([caused]), complemento([inhibition, of, transcription, 'factor-induced', 'Th2', cytokine, gene, expression])]). relacion([sujeto(['RHS6', is, a, critical, regulatory, element, for, allergic, airway, inflammation, and, for, coordinate, regulation, of, 'Th2', cytokine, genes, by]), verbo([recruiting]), complemento(['GATA3,', 'SATB1,', and, 'IRF4'])]). relacion([sujeto([subintegrum]), verbo([has]), complemento([been, used, as, traditional, medicine, to, treat, inflammatory, diseases])]). relacion([sujeto(['In', this, 'study,', we, assessed, whether, picroside, 'II']), verbo([has]), complemento([inhibitory, effects, on, airway, inflammation, in, a, mouse, model, of, house, dust, mite, '(', 'HDM)-induced', asthma])]). relacion([sujeto(['Picroside', 'II', also]), verbo([inhibited]), complemento([the, expression, of, 'Th2', type, cytokine, genes, and, the, transcription, factor, 'GATA3', in, the, lung, tissues, of, 'HDM-induced', mice])]). relacion([sujeto(['Finally,', we, demonstrated, that, picroside, 'II', significantly]), verbo([decreased]), complemento([the, expression, of, 'GATA3', and, 'Th2', cytokines, in, developing, 'Th2', 'cells,', consistent, with, in, vivo, results])]). relacion([sujeto(['Taken', 'together,', these, results, indicate, that, picroside, 'II']), verbo([has]), complemento([protective, effects, on, allergic, asthma, by, reducing, 'GATA3', expression, and, 'Th2', cytokine, bias])]). relacion([sujeto(['Mucosal', expression, of, 'T', helper, '(', 'Th)', 'cell-lineage', specific, transcription, factors, '(', 'Tbet,', 'Gata3,', 'Rorc,', 'FoxP3)', before, treatment, was, also]), verbo([associated]), complemento([with, mucosal, healing])]). relacion([sujeto(['Mucosal', healing, was]), verbo([associated]), complemento([with, lower, 'pre-treatment', mucosal, expression, of, transcription, factor, 'Th1-Tbet', '(', 'p<0'])]). relacion([sujeto(['Mucosal', healing, was]), verbo([associated]), complemento([with, combination, 'therapy,', especially, in, biologic, and, 'azathioprine-naïve', patients, and, 'pre-treatment', mucosal, expression, of, specific, 'Th', specific, transcripting, factors, '(', 'Tbet', and, 'Rorc)'])]). relacion([sujeto(['The', present, study, was, designed, to, investigate, the, upstream, transcription, factors, '(', 'TFs)', and, the, signature, genes, in, cholangiocarcinoma, '(', 'CCA),']), verbo([providing]), complemento([better, clues, on, the, regulatory, mechanisms, and, therapeutic, applications])]). relacion([sujeto(['Functional', annotation, of, differently]), verbo([expressed]), complemento([genes, '(', 'DEGs)', was, then, conducted, and, the, 'TFs', were, identified])]). relacion([sujeto(['Integrated', analysis, of, five, eligible, 'Gene', 'Expression', 'Omnibus', data, sets]), verbo([led]), complemento([to, a, set, of, 993, 'DEGs', and, 48, 'TFs', in, 'CCA'])]). relacion([sujeto(['The', top, 10, 'TFs', covering, the, most, downstream, 'DEGs', were, 'NFATC2,', 'SOX10,', 'ARID3A,', 'ZNF263,', 'NR4A2,', 'GATA3,', 'EGR1,', 'PLAG1,', 'STAT3', and, 'FOSL1,', which, may]), verbo([have]), complemento([important, roles, in, the, tumorigenesis, of, 'CCA'])]). relacion([sujeto(['Supporting', the, fact, that, defects, of, 'cell-cycle', surveillance, mechanism, were, closely, related, to, various, 'cancers,', we]), verbo([found]), complemento([that, cell, cycle, was, the, most, significantly, enriched, pathway])]). relacion([sujeto(['KCNN2', and, 'ADCY6', were]), verbo([involved]), complemento([in, the, bile, secretion])]). relacion([sujeto(['Particularly,', we]), verbo([found]), complemento([that, upregulation, of, 'EZH2', in, 'CCA', is, a, powerful, potential, marker, for, 'CCA'])]). relacion([sujeto(['Histologically,', two, cases, showed, mucosal, '(', or, 'skin)-based', mass, lesions, with]), verbo([associated]), complemento([pagetoid, spread, in, the, adjacent, 'epithelium,', a, feature, normally, associated, with, primary, carcinomas])]). relacion([sujeto(['Although', technological, advances, now, allow]), verbo([increased]), complemento([tumor, 'profiling,', a, detailed, understanding, of, the, mechanisms, leading, to, the, development, of, different, cancers, remains, elusive])]). relacion([sujeto(['Our', approach, toward, understanding, the, molecular, events, that]), verbo([lead]), complemento([to, cancer, is, to, characterize, changes, in, transcriptional, regulatory, networks, between, normal, and, tumor, tissue])]). relacion([sujeto(['Because', enhancer, activity, is, thought, to, be, critical, in]), verbo([regulating]), complemento([cell, fate, 'decisions,', we, have, focused, our, studies, on, distal, regulatory, elements, and, transcription, factors, that, bind, to, these, elements])]). relacion([sujeto(['Using', 'DNA', methylation, 'data,', we, identified, more, than, 25, ',', 0, enhancers, that, are, differentially]), verbo([activated]), complemento([in, 'breast,', 'prostate,', and, kidney, tumor, 'tissues,', as, compared, to, normal, tissues])]). relacion([sujeto(['We']), verbo([found]), complemento([more, than, 1200, transcription, factors, to, be, involved, in, these, 'tumor-specific', enhancer, networks])]). relacion([sujeto(['We', showed, that, 'HOXC6', and, 'DLX1', are]), verbo([associated]), complemento([with, different, clusters, of, prostate, 'tumor-specific', enhancers, and, confer, distinct, transcriptomic, changes, upon, knockdown, in, 'C42B', prostate, cancer, cells])]). relacion([sujeto(['Our', studies, characterized, 'tumor-specific', enhancers, and, revealed, key, transcription, factors]), verbo([involved]), complemento([in, enhancer, networks, for, specific, tumor, types, and, subgroups])]). relacion([sujeto(['Our', 'findings,', which, include, a, large, set, of, identified, enhancers, and, transcription, factors, linked, to, those, enhancers, in, 'breast,', 'prostate,', and, kidney, 'cancers,', will, facilitate, understanding, of, enhancer, networks, and, mechanisms]), verbo([leading]), complemento([to, the, development, of, these, cancers])]). relacion([sujeto(['While', traditional, oncology, screens, commonly, use, a, single, endpoint, of, cell, 'viability,', altering, the, phenotype, of, 'tumor-initiating', cells, may]), verbo([reveal]), complemento([alternative, targets, that, regulate, cellular, growth, by, processes, other, than, apoptosis, or, cell, division])]). relacion([sujeto(['We', evaluated, the, impact, of, knocking, down, expression, of, 420, kinases, in, 'bi-lineage', 'triple-negative', breast, cancer, '(', 'TNBC)', cells, that]), verbo([express]), complemento([characteristics, of, both, myoepithelial, and, luminal, cells])]). relacion([sujeto(['Knockdown', of, 'ERN1', or, 'ALPK1']), verbo([induces]), complemento(['bi-lineage', 'MDA-MB-468', cells, to, lose, the, myoepithelial, marker, keratin, 5, but, not, the, luminal, markers, keratin, 8, and, 'GATA3'])]). relacion([sujeto(['In', 'addition,', these, cells, exhibit]), verbo([increased]), complemento(['β-casein', production])]). relacion([sujeto(['These', changes, are]), verbo([associated]), complemento([with, decreased, proliferation, and, clonogenicity, in, spheroid, cultures, and, 'anchorage-independent', growth, assays])]). relacion([sujeto(['This', study, supports, the, strategy, to, identify, new, molecular]), verbo([targets]), complemento([for, types, of, cancer, driven, by, cells, that, retain, some, capacity, for, normal, differentiation, to, a, 'non-tumorigenic', phenotype])]). relacion([sujeto(['ERN1', and, 'ALPK1', are, potential]), verbo([targets]), complemento([for, therapeutic, development])]). relacion([sujeto(['To']), verbo([report]), complemento([a, rare, case, of, vitreoretinal, metastasis, from, urothelial, carcinoma, of, the, bladder])]). relacion([sujeto(['Alveolar', capillary, dysplasia, with, misalignment, of, pulmonary, veins, '(', 'ACDMPV)', is, a, rare, lethal, lung, developmental, disorder]), verbo([caused]), complemento([by, heterozygous, point, mutations, or, genomic, deletions, involving, 'FOXF1', or, its, 60, -, kb, 'tissue-specific', enhancer, region, mapping, 270, &, 'nbsp;kb', upstream, of, 'FOXF1', and, involving, fetal, 'lung-expressed', long, 'non-coding', 'RNA', genes, and, 'CpG-enriched', sites])]). relacion([sujeto(['Recently,', we]), verbo([have]), complemento([proposed, that, the, 'FOXF1', locus, at, 16, q24])]). relacion([sujeto(['Using', 'custom-designed', aCGH, and, 'Sanger', 'sequencing,', we]), verbo([have]), complemento([identified, a, novel, de, novo, 104, &, 'nbsp;kb', genomic, deletion, upstream, of, 'FOXF1', in, a, patient, with, histopathologically, verified, full, phenotype, of, 'ACDMPV'])]). relacion([sujeto(['This', interval, harbors]), verbo([binding]), complemento([sites, for, 'lung-expressed', transcription, 'factors,', including, 'GATA3,', 'ESR1,', and, 'YY1,', and, is, flanked, by, the, lncRNA, genes, and, 'CpG', islands])]). relacion([sujeto([1]), verbo([provided]), complemento([new, insights, into, its, regulatory, function, and, genomic, imprinting])]). relacion([sujeto(['Small', sample, size, and, the]), verbo([loss]), complemento([of, some, patients, to, 'follow-up'])]). relacion([sujeto(['TH1', cytokines, can]), verbo([recruit]), complemento(['histiocytes,', a, source, of, 'elastases,', and, upregulate, matrix, metalloproteinase, 'activity,', which, may, contribute, to, epidermal, atrophy])]). relacion([sujeto(['Acute', chorioamnionitis, contributes, to, premature, 'birth,', and, is]), verbo([associated]), complemento([with, 'post-birth', complications])]). relacion([sujeto(['How', chorioamnionitis, impacts, 'neonate\'s', developing, immune, system]), verbo([has]), complemento([not, been, well, defined])]). relacion([sujeto(['Blood', was, either, left, unstimulated, or]), verbo([stimulated]), complemento([for, 4, hours, with, 'PMA/ionomycin'])]). relacion([sujeto([mRNA, expression, of, transcription, factors, in, unstimulated, cells, '(', 'RORC,', 'TBET,', 'GATA3,', 'FOXP3)', and, inflammatory, cytokines, '(', 'IFN-γ,', 'TNF-α,', 'IL-2,', 'IL-4,', 'IL-5,', and, 'IL-6)', in, unstimulated, and]), verbo([stimulated]), complemento([cells, were, analyzed])]). relacion([sujeto(['At', 1, week, of, 'life,', exposure, to, 'funisitis,', but, not, maternal, chorioamnionitis, was]), verbo([associated]), complemento([with, an, increased, expression, of, 'RORC', and, 'RORC/FOXP3', ratio])]). relacion([sujeto(['These']), verbo([increases]), complemento([in, 'RORC', and, 'RORC/FOXP3', ration, were, sustained, over, the, 4, weeks, of, 'follow-up'])]). relacion([sujeto(['Leukocytes', from, infants, who, developed, 'BPD', had]), verbo([increased]), complemento([stimulated, and, unstimulated, 'IL-4', at, the, 1, '(', 'st)', week, of, 'life,', but, these, increases, were, not, sustained, over, time])]). relacion([sujeto(['In', 'contrast,', infants, with, mild, 'BPD', had, a, sustained]), verbo([decrease]), complemento([in, stimulated, 'IL-2'])]). relacion([sujeto(['Chorioamnionitis', 'exposure,', in, particular, to, 'funisitis,']), verbo([lead]), complemento([to, enhanced, 'Th17-like', responses, that, persist, for, 4, weeks, after, birth])]). relacion([sujeto(['GATA3', and, 'T-box', '(', 'T-bet)']), verbo([expressed]), complemento([in, 'T-cells', are, transcriptional, factors, that, play, a, critical, role, in, development, of, 'Th2', and, 'Th1', immunity, respectively])]). relacion([sujeto(['GATA3', is]), verbo([expressed]), complemento([during, 'Th2', differentiation, and, 'T-bet', is, expressed, exclusively, in, 'Th1', cells])]). relacion([sujeto(['T-bet', was]), verbo([expressed]), complemento([significantly, in, 60, &, 'nbsp;%', of, acute, 'ITP', children, '(', 12, /, 20, ')', '(', 'P', value, 0.001, ')', and, not, expressed, in, persistent, 'ITP', children, '(', 0, /, 20, ')', ',', while, 'GATA3', was, expressed, in, 25, &, 'nbsp;%', of, persistent, 'ITP', patients, '(', 5, /, 20, ')', '(', 'P', value, 0.017, ')', and, not, expressed, in, acute, 'ITP', patients, '(', 0, /, 20, ')'])]). relacion([sujeto(['Intensive', studies, of, abnormal, cytokine, profiles, in, 'ITP']), verbo([have]), complemento([led, to, cytokine, therapies, that, exploit, the, effects, of, 'IFN-γ', on, 'Th2', 'cells,', but, such, therapies, are, often, ineffective, to, develop, safe, and, effective, therapeutic, tools])]). relacion([sujeto(['To']), verbo([provide]), complemento([novel, insights, into, the, regulatory, molecular, mechanisms, of, the, 'disease,', we, performed, 'RNA', sequencing, analysis, of, 14, pairs, of, skin, samples, collected, from, patients, with, psoriasis])]). relacion([sujeto(['Subsequent', pathway, analysis, and, extraction, of, the, transcriptional, regulators, governing, 'psoriasis-associated', pathways, was]), verbo([executed]), complemento([using, a, combination, of, the, 'MetaCore', 'Interactome', enrichment, tool, and, the, cisExpress, 'algorithm,', followed, by, comparison, to, a, set, of, previously, described, psoriasis, response, elements])]). relacion([sujeto(['A', comparative, approach, allowed, us, to, identify, 42, core, transcriptional, regulators, of, the, disease]), verbo([associated]), complemento([with, inflammation, '(', 'NFκB,', 'IRF9,', 'JUN,', 'FOS,', 'SRF),', the, activity, of, 'T', cells, in, psoriatic, lesions, '(', 'STAT6,', 'FOXP3,', 'NFATC2,', 'GATA3,', 'TCF7,', 'RUNX1),', the, hyperproliferation, and, migration, of, keratinocytes, '(', 'JUN,', 'FOS,', 'NFIB,', 'TFAP2A,', 'TFAP2C)', and, lipid, metabolism, '(', 'TFAP2,', 'RARA,', 'VDR)'])]). relacion([sujeto(['In', addition, to, the, core, 'regulators,', we, identified, 38, transcription, factors, previously, not]), verbo([associated]), complemento([with, the, disease, that, can, clarify, the, pathogenesis, of, psoriasis])]). relacion([sujeto(['Using', 'ChIP-seq', and, 'RNA-seq', 'data,', we, concluded, that, the, atypical, expression, of, the, 'FOXA1', 'TF', is, an, important, player, in, the, disease, as, it]), verbo([inhibits]), complemento([the, maturation, of, naive, 'T', cells, into, the, '(', 'CD4+FOXA1+CD47+CD69+PD-L1(hi)FOXP3-)', regulatory, 'T', cell, 'subpopulation,', therefore, contributing, to, the, development, of, psoriatic, skin, lesions])]). relacion([sujeto(['Then,', functional, annotation, of, differentially]), verbo([expressed]), complemento([genes, '(', 'DEGs)', was, 'conducted,', including, 'Gene', 'Ontology', '(', 'GO)', enrichment, and, 'Kyoto', 'Encyclopedia', of, 'Genes', and, 'Genomes', '(', 'KEGG)', pathway, enrichment])]). relacion([sujeto(['Fifty-three', differentially]), verbo([expressed]), complemento(['TFs', were, 'identified,', and, the, regulatory, networks, consisted, of, 817, 'TF-target', interactions, between, 46, 'TFs', and, 602, 'DEGs', in, the, context, of, breast, cancer])]). relacion([sujeto(['The', transcriptional, regulatory, networks, could, enable, a, better, understanding, of, regulatory, mechanisms, of, breast, cancer, pathology, and]), verbo([provide]), complemento([an, opportunity, for, the, development, of, potential, therapy])]). relacion([sujeto([γδ, regulatory, 'T', cells, are, able, to]), verbo([inhibit]), complemento([the, activation, and, function, of, 'T', cells, involved, in, 'antigen-specific', immune, responses])]). relacion([sujeto(['This', study, aimed, to, investigate, the, potential, role, of, γδ, regulatory, 'T', cells, in]), verbo([inhibiting]), complemento(['anti-tumor', immune, responses, in, patients, diagnosed, as, multiple, myeloma, '(', 'MM)'])]). relacion([sujeto(['In', 'addition,', we, evaluated, the, ability, of, γδ, regulatory, 'T', cells, to]), verbo([inhibit]), complemento([the, proliferation, of, 'CD4+CD25-', 'T', cells, and, detected, the, expression, of, 'immunoregulatory-associated', molecules])]). relacion([sujeto(['We']), verbo([found]), complemento([that, the, levels, of, γδ, regulatory, 'T', cells, from, the, peripheral, blood, in, patients, of, 'MM', were, significantly, higher, than, those, in, healthy, donors])]). relacion([sujeto(['Additionally,', 'TLR8', expression, level]), verbo([increased]), complemento([significantly, in, 'MM', patients, compared, to, healthy, 'donors,', while, the, expression, levels, of, 'Foxp3,', 'CD25,', 'CTLA4,', 'GITR,', 'GATA3', and, 'Tbet', in, 'MM', patients, and, healthy, donors, showed, no, significant, difference])]). relacion([sujeto(['Taken', 'together,', our, study]), verbo([reveals]), complemento([the, potential, role, of, γδ, regulatory, 'T', cells, in, inhibiting, 'anti-tumor', immune, responses, in, 'MM', patients])]). relacion([sujeto(['Gene', expression, of, transcription, factors, and, cytokines]), verbo([involved]), complemento([in, differentiation, and, effector, function, of, 'T', cell, 'subsets,', regulatory, 'T', cells, and, follicular, 'Th', 'cells,', were, analyzed, in, the, blood, from, 21, newly, diagnosed, adult, and, 26, juvenile, 'DM', subjects, and, in, 15, muscle, specimens, '(', 7, adult, and, 8, juvenile, 'DM)', using, a, custom, 'RT2', 'Profiler', 'PCR', 'Array'])]). relacion([sujeto(['The', most, prominent]), verbo([finding]), complemento([was, the, higher, blood, expression, of, 'Th17-related', cytokines, '[', retinoic, 'acid-related', orphan, 'receptor-γ,', interferon, regulatory, factor, 4, ',', interleukin, '(', 'IL)-23A,', 'IL-6,', 'IL-17F,', and, 'IL-21]', in, juvenile, 'DM', at, baseline])]). relacion([sujeto(['In', 'contrast,', adult, patients, with, 'DM', showed]), verbo([increased]), complemento([blood, levels, of, 'STAT3', and, 'BCL6', compared, with, juvenile, 'DM'])]). relacion([sujeto(['In', 'muscle,', 'GATA3,', 'IL-13,', and, 'STAT5B', were]), verbo([found]), complemento([at, higher, levels, in, juvenile, patients, with, 'DM', compared, with, adult, 'DM'])]). relacion([sujeto(['Among', 25, patients, '(', 11, adult, and, 14, juvenile, 'DM)', who, had, blood, samples, at, baseline, and, at, 6, 'months,']), verbo([increased]), complemento([expression, of, 'IL-1β,', 'STAT3,', 'STAT6,', 'STAT5B,', and, 'BCL6', was, associated, with, an, improvement, in, global, extramuscular, disease, activity])]). relacion([sujeto(['Serotonergic', and, glutamatergic, neurons, of, the, dorsal, raphe]), verbo([regulate]), complemento([many, brain, functions, and, are, important, for, mental, health])]). relacion([sujeto(['The', newly, born, serotonergic, precursors, are, segregated, into, distinct, subpopulations]), verbo([expressing]), complemento([vesicular, glutamate, transporter, 3, '(', 'Vglut3)', or, serotonin, transporter, '(', 'Sert)'])]). relacion([sujeto(['These', populations, differ, in, their, requirements, for, transcription, factors, 'Gata2', and, 'Gata3,', which, are]), verbo([activated]), complemento([in, the, 'post-mitotic', precursors])]). relacion([sujeto(['Similar', to, the, serotonergic, 'neurons,', the, 'Vglut3-expressing', glutamatergic, 'neurons,', located, in, the, central, dorsal, 'raphe,', are, derived, from, neural, progenitors, in, the, ventral, hindbrain, and]), verbo([express]), complemento(['Pet1', 'Furthermore,', both, 'Gata2', and, 'Gata3', are, redundantly, required, for, their, differentiation])]). relacion([sujeto(['Our', study, demonstrates, lineage, relationships, of, the, dorsal, raphe, neurons, and]), verbo([suggests]), complemento([that, functionally, significant, heterogeneity, of, these, neurons, is, established, early, during, their, differentiation])]). relacion([sujeto(['Although', fusion, genes, generated, by, chromosomal, rearrangements, are, the, most, frequent, genetic, alterations, in, pediatric, 'ALL,', fusions, are, insufficient, for, the, development, of, this, 'disease,', and, 'thus,', cannot, serve, as, therapeutic]), verbo([targets]), complemento([for, 'ALL'])]). relacion([sujeto(['Recently,', integrated, genetic, analysis, using, next, generation, sequencing, technology]), verbo([has]), complemento([revealed, the, genetic, landscapes, of, pediatric, 'ALL'])]). relacion([sujeto(['These', studies, disclosed, that, in, addition, to, fusion, 'genes,', aberrations, of, cell, proliferation, pathways, and, epigenetic, regulations, are, also]), verbo([involved]), complemento([in, the, pathogenesis, of, pediatric, 'ALL'])]). relacion([sujeto(['On', the, other, 'hand,', more, 'recently,', abnormalities, of, supper, enhancer, regions, of, 'TAL1']), verbo([have]), complemento([been, detected, as, a, novel, oncogenic, mechanism, of, pediatric, 'T', cell, 'ALL'])]). relacion([sujeto(['Furthermore,', germline, mutations, of, 'ARID5B,', 'PAX5,', and, 'GATA3']), verbo([have]), complemento([been, found, to, be, involved, in, the, genetic, risk, of, developing, 'ALL'])]). relacion([sujeto(['Therefore,', 'currently,', the, molecular, mechanisms, of, pediatric, 'ALL']), verbo([have]), complemento([been, fully, disclosed])]). relacion([sujeto(['We']), verbo([report]), complemento([a, series, of, 7, unusual, and, morphologically, distinct, cervical, or, upper, vaginal, lesions, in, women, aged, 41, to, 70, years])]). relacion([sujeto(['The', lesions]), verbo([involved]), complemento([the, cervix, in, 3, 'cases,', the, upper, vagina, in, 2, ',', the, cervix, and, vagina, in, 1, ',', and, in, 1, case, the, site, of, origin, could, not, be, determined])]). relacion([sujeto(['Rarely,', similar, cases]), verbo([have]), complemento([been, reported, previously, as, inverted, transitional, papilloma, of, the, cervix, or, 'vagina,', but, based, on, the, morphology, and, immunophenotype, we, do, not, feel, these, represent, transitional, lesions])]). relacion([sujeto(['We']), verbo([suggest]), complemento([the, term, seborrheic, 'keratosis-like', lesions, to, designate, this, new, and, rare, 'entity,', which, may, be, associated, with, 'low-risk', human, papillomavirus, infection])]). relacion([sujeto(['Limited', 'follow-up', in, a, small, number, of, cases]), verbo([suggests]), complemento([that, these, lesions, follow, a, benign, clinical, course])]). relacion([sujeto(['BACKGROUND', 'Specific', 'T', cell, phenotype]), verbo([has]), complemento([been, reported, to, potentially, contribute, to, the, development, of, angiotensin, 'II', '(', 'Ang', 'II)-induced', several, vascular, disorders])]). relacion([sujeto(['Type', 2, diabetes, mellitus, '(', 'T2DM)', is, intimately]), verbo([associated]), complemento([with, cardiovascular, disease])]). relacion([sujeto(['Th1', and, 'Th17', positive, 'cells,', mRNA, levels, of, 'T-bet', and, 'RORgt', as, well, as, the, expression, of, 'IFN-γ', and, 'IL-17', were, significantly]), verbo([increased]), complemento([in, the, 'CA', group, compared, with, the, 'T2DM', group, and, control, group, '(', 'p<0'])]). relacion([sujeto(['Moreover,', the, activities, of, 'T', cells, and, related, cytokines, were, significantly]), verbo([increased]), complemento([of, healthy, controls, after, 'Ang', 'II', treatment, '(', 'p<0'])]). relacion([sujeto(['CONCLUSIONS', 'Ang', 'II']), verbo([promotes]), complemento([the, development, of, 'CA', in, 'T2DM', patients, by, regulating, 'T', cells, activities])]). relacion([sujeto(['It']), verbo([has]), complemento([been, suggested, that, bladder, cancer, can, be, divided, into, two, molecular, subtypes, referred, to, as, luminal, and, basal, with, distinct, clinical, behaviors, and, sensitivities, to, chemotherapy])]). relacion([sujeto(['They', showed, the, upregulation, of, 'PPARγ']), verbo([target]), complemento([genes, and, the, enrichment, for, 'FGFR3,', 'ELF3,', 'CDKN1A,', and, 'TSC1', mutations])]). relacion([sujeto(['They', showed, the, upregulation, of, p63]), verbo([target]), complemento(['genes,', the, enrichment, for, 'TP53', and, 'RB1', 'mutations,', and, overexpression, of, 'CD49,', 'Cyclin', 'B1,', and, 'EGFR'])]). relacion([sujeto(['The', molecular, subtypes, of, bladder, cancer]), verbo([have]), complemento([distinct, clinical, behaviors, and, sensitivities, to, 'chemotherapy,', and, a, simple, 'two-marker', immunohistochemical, classifier, can, be, used, for, prognostic, and, therapeutic, stratification])]). relacion([sujeto(['A', statistically, significant, association, was, observed, for, 'BCG', failure, with, low, density, of, 'CD4+', and, 'GATA3+', 'T-cells,', and]), verbo([increased]), complemento([expression, of, 'FOXP3+', and, 'CD25+', regulatory, 'T-cells', '(', 'Tregs)', as, well, as, 'CD68+', and, 'CD163+', 'TAMs'])]). relacion([sujeto(['Survival', analysis, demonstrated, prolonged, 'recurrence-free', survival, '(', 'RFS)', in, patients, with, an]), verbo([increased]), complemento([count, of, 'CD4+', and, 'GATA3+', 'T-cells'])]). relacion([sujeto(['However,', 'PD-L1', expression, in, association, with, subtypes, of, 'tumor-associated', lymphocytes, and, molecular, alterations]), verbo([has]), complemento([not, been, well, characterized, in, lung, adenocarcinomas])]). relacion([sujeto(['PD-L1', expression, was]), verbo([associated]), complemento([with, abundant, 'CD8(+)', 'and/or', 'T-bet(+)', 'tumor-infiltrating', lymphocytes, and, 'EGFR', 'wild-type,', significant, smoking, 'history,', and, aggressive, pathologic, features])]). relacion([sujeto(['PD-L1', expression, was, significantly]), verbo([associated]), complemento([with, decreased, 'progression-free', and, overall, survival, rates, by, univariate, 'analysis,', but, not, by, multivariate, analysis])]). relacion([sujeto(['PD-L1', expression, in, resected, lung, adenocarcinomas, is, frequently, observed, in, the, presence, of, 'CTL/Th1', 'microenvironment,', in, particular, in, those, with, 'KRAS', mutations, or, no, common, molecular, 'alterations,']), verbo([suggesting]), complemento([that, blockade, of, the, 'PD-1/PD-L1', axis, may, be, a, promising, treatment, strategy, to, reinstitute, active, immune, response, for, at, least, a, subset, of, such, patient, populations])]). relacion([sujeto(['Although', these, processes, are, driven, by, transcription, factors, such, as, 'HOXB4', and, 'GATA3,', there, is, no, evidence, that, 'Notch', directly]), verbo([regulates]), complemento([their, transcription])]). relacion([sujeto(['The', use, of, a, 'Notch', signaling, inhibitor, and, a, protein, synthesis, inhibitor, allowed, us, to, distinguish, primary, 'effects,']), verbo([mediated]), complemento([by, direct, signaling, downstream, 'Notch', and, 'TNF,', from, secondary, 'effects,', mediated, by, de, novo, synthesized, proteins])]). relacion([sujeto(['A', low, and, physiologically, relevant, concentration, of, 'TNF']), verbo([promoted]), complemento(['T', lymphopoiesis, in, 'OP9-DL1', cocultures])]). relacion([sujeto(['TNF', positively]), verbo([modulated]), complemento([the, expression, of, both, transcripts, in, a, 'Notch-dependent', 'manner;', 'however,', 'GATA3', induction, was, mediated, by, a, direct, 'mechanism,', while, 'HOXB4', induction, was, indirect])]). relacion([sujeto(['Induction', of, both, transcripts, was, repressed, by, a, 'GSK3β', 'inhibitor,', indicating, that, activation, of, canonical, 'Wnt', signaling]), verbo([inhibits]), complemento([rather, than, induces, their, expression])]). relacion([sujeto(['Our', study]), verbo([provides]), complemento([novel, evidences, of, the, mechanisms, integrating, 'Notch', and, 'TNF-alpha', signaling, in, the, transcriptional, induction, of, 'GATA3', and, 'HOXB4'])]). relacion([sujeto(['This', mechanism]), verbo([has]), complemento([direct, implications, in, the, control, of, 'self-renewal,', 'proliferation,', 'commitment,', and, 'T', cell, differentiation])]). relacion([sujeto(['In', spite, of, hyporesponsivity, to, 'Mycobacterium', 'leprae,', borderline, lepromatous, '(', 'BL)', patients, show, clinical, and, immunological, 'instability,', and, undergo, frequent, acute, inflammatory, episodes, such, as, type, 1, reaction, '(', 'T1R),', which, may]), verbo([cause]), complemento([nerve, damages])]). relacion([sujeto(['We', observed, a, significantly]), verbo([increased]), complemento([ex, vivo, frequency, of, both, effector, and, memory, 'CD4+', and, 'CD8+', 'T', cells, in, 'T1R', group])]). relacion([sujeto(['Besides,', ex, vivo, frequency, of, 'T', cell, homing, 'receptor,', the, 'Cutaneous', 'Leukocyte-associated', 'Antigen', '(', 'CLA)', was, significantly]), verbo([increased]), complemento([in, 'T', cells, from, 'T1R', patients])]). relacion([sujeto([leprae]), verbo([induced]), complemento([a, higher, frequency, of, 'CD4+', 'TEM', and, 'CD8+', 'TEF', 'cells,', as, well, as, of, 'CD8+/TEMRA', '(', terminally, differentiated, effector, 'T', 'cells)', 'subset,', which, expressed, high, 'CD69+'])]). relacion([sujeto(['TBX21', expression, was, significantly, higher, in, 'T1R,', while, 'BL', showed]), verbo([increased]), complemento(['GATA3', and, 'FOXP3', expression])]). relacion([sujeto(['The', observed]), verbo([increase]), complemento([of, ex, vivo, 'T', cells, at, 'T1R', onset, suggests, intravascular, activation, at, the, beginning, of, reactional, episodes])]). relacion([sujeto(['The', 'antigen-specific', response, in, 'T1R', group, confirmed, the, higher, number, of, 'CD8+/CLA+', and, 'CD45RA+/CLA+', cells, in, 'T1R', lesions]), verbo([suggests]), complemento([possible, migration, of, these, cells, activated, by, 'M'])]). relacion([sujeto(['We', investigated, the, effect, of, 'DWac', on, the, gut, microbiota, composition, in, mice, with, 2, ',', 3, ',', 6, -, trinitrobenzenesulfonic, 'acid-', '(', 'TNBS-)']), verbo([induced]), complemento([colitis])]). relacion([sujeto(['Intrarectal', injection, of, 'TNBS', in, 'MRC', mice]), verbo([caused]), complemento([severe, 'colitis,', as, well, as, colon, 'shortening,', 'edema,', and, increased, myeloperoxidase, activity])]). relacion([sujeto(['Treatment', with, 'DWac', and, its, mixture, with, mesalazine]), verbo([inhibited]), complemento(['TNBS-induced', activation, of, 'NF-κB', and, expression, of, 'M1', macrophage, markers, but, increased, 'TNBS-suppressed', expression, of, 'M2', macrophage, markers])]). relacion([sujeto(['Furthermore,', these]), verbo([inhibited]), complemento(['TNBS-induced', 'T-bet,', 'RORγt,', 'TNF-α,', and, 'IL-17', expression, but, increased, 'TNBS-suppressed', 'Foxp3', and, 'IL-10', expression])]). relacion([sujeto(['These', findings]), verbo([suggest]), complemento([that, 'DWac', can, ameliorate, 'MRC', by, increasing, the, polarization, of, 'M2', macrophage, and, correcting, the, disturbance, of, gut, microbiota, and, 'Th1/Th17/Treg,', as, well, as, additively, attenuating, 'MRC', along, with, mesalazine])]). relacion([sujeto(['Although', high, expression, of, 'PD-L1', in, tumor, tissues]), verbo([has]), complemento([been, implicated, to, correlate, with, the, better, response, to, the, 'anti-PD-1', 'therapies,', this, association, has, been, controversial])]). relacion([sujeto(['We']), verbo([found]), complemento(['that,', in, addition, to, the, 'PD-L1', '(', p, =, 0.03, ')', ',', expression, levels, of, 'PD-1', 'ligand-2', '(', 'PD-L2),', granzyme, 'A', '(', 'GZMA)', and, human, leukocyte, 'antigen-A', '(', 'HLA-A)', in, the, 'pre-treatment', tumors, were, significantly, higher, '(', p, =, 0.04, ',', p, =, 0.01, and, p, =, 0.006, ',', 'respectively)', in, responders, '(', n, =, 5, ')', than, in, 'non-responders', '(', n, =, 8, ')'])]). relacion([sujeto(['With', nivolumab, 'treatment,', tumors, in, responders, exhibited, a, substantial]), verbo([increase]), complemento([of, 'CD8,', 'GZMA', and, perforin, 1, '(', 'PRF1)', expression, levels, as, well, as, increased, ratio, of, 'TBX21/GATA3,', suggesting, dominancy, of, helper, 'T', cell, type, 1, '(', 'Th1)', response, to, type, 2, '(', 'Th2)', response])]). relacion([sujeto(['Our', findings]), verbo([suggest]), complemento([that, melanoma, harboring, high, 'PD-1', ligands, '(', 'PD-L1', and, 'PD-L2),', 'GZMA', and, 'HLA-A', expression, may, respond, preferentially, to, nivolumab, 'treatment,', which, can, enhance, 'Th1-skewed', cellular, immunity, with, oligoclonal, expansion, of, 'TILs'])]). relacion([sujeto(['CD4(+)', 'T', cell, activation, and, adequate, differentiation, into, effector, 'T', helper, '(', 'Th)', cells, are, crucial, for]), verbo([mediating]), complemento([adaptive, immune, responses, to, cope, with, foreign, pathogens])]). relacion([sujeto(['Despite', the, significant, role, of, 'Th', 'cells,', excessive]), verbo([increases]), complemento([in, their, numbers, result, in, inflammatory, and, autoimmune, diseases])]). relacion([sujeto(['In', this, 'study,', we, investigated, the, effects, of, 'costunolide,', a, 'plant-derived', natural, compound, with, an, 'anti-inflammatory', 'activity,', in]), verbo([regulating]), complemento(['Th', cells, and, the, underlying, mechanisms])]). relacion([sujeto(['Costunolide', significantly]), verbo([decreased]), complemento([cell, populations, of, differentiated, 'Th1,', 'Th2,', and, 'Th17', subsets, under, 'Th', 'subset-polarizing', 'conditions,', while, exerting, statistically, negligible, effects, on, 'Treg', cell, differentiation])]). relacion([sujeto(['Furthermore,', costunolide]), verbo([inhibited]), complemento([the, expression, level, of, 'Th', 'subset-polarizing', master, genes, such, as, 'T-bet,', 'GATA3,', and, 'RORγt,', indicating, that, costunolide, inhibits, the, differentiation, of, 'CD4(+)', 'T', cells, into, 'Th', subsets])]). relacion([sujeto(['Additionally,', costunolide]), verbo([suppressed]), complemento([the, proliferative, activity, of, 'CD4(+)', 'T', cells, and, the, expression, of, 'CD69', activation, marker, on, 'CD4(+)', 'T', cells])]). relacion([sujeto(['When', the, molecular]), verbo([targets]), complemento([of, costunolide, were, 'investigated,', phosphorylation, of, 'ERK', and, p38, was, found, to, be, decreased, under, 'Th', 'subset-polarizing', 'conditions,', whereas, activity, of, 'JNK', remained, unchanged])]). relacion([sujeto(['U0126,', an, 'ERK', 'inhibitor,', and, 'SB203580,', a, p38, 'inhibitor,']), verbo([decreased]), complemento([the, expression, of, 'CD69', upon, 'TCR', stimulation, and, inhibited, 'CD4(+)', 'T', cell, 'differentiation,', indicating, that, both, 'ERK', and, p38, are, suggested, to, be, critical, molecular, targets, of, costunolide])]). relacion([sujeto(['Taken', 'together,', these, results]), verbo([suggest]), complemento([that, costunolide, inhibits, the, differentiation, of, 'CD4(+)', 'T', cells, by, suppressing, 'ERK', and, p38, activities, and, can, be, an, effective, therapeutic, agent, for, 'T', 'cell-mediated', immune, diseases])]). relacion([sujeto(['Pregnancies', resulting, from, fresh, in, vitro, fertilization, '(', 'IVF)', cycles, exposed, to, supraphysiologic, estrogen, levels]), verbo([have]), complemento([been, associated, with, higher, rates, of, low, birth, weight, and, small, for, gestational, age, babies])]). relacion([sujeto(['We', identified, 'GATA3,', a, transcription, factor, selectively]), verbo([expressed]), complemento([in, the, trophectoderm, during, the, blastocyst, stage, of, embryo, 'development,', in, an, upstream, analysis, of, genes, that, were, differentially, methylated, in, chorionic, villus, samples, between, 'IVF', and, 'non-IVF', infertility, treatment, pregnancies])]). relacion([sujeto(['In', this, 'study,', we, investigate, the, hypothesis, that, 'GATA3', is, hormonally]), verbo([regulated]), complemento([and, plays, an, important, functional, role, in, trophoblast, 'migration,', 'invasion,', and, placentation])]). relacion([sujeto(['We']), verbo([found]), complemento([that, 'GATA3', expression, was, hormonally, regulated, by, estradiol, in, 'HTR8/SVneo', first, trimester, trophoblast, 'cells;', 'however,', no, change, in, expression, was, seen, with, progesterone, treatment])]). relacion([sujeto(['Furthermore,', 'GATA3', knockdown, resulted, in]), verbo([decreased]), complemento(['HTR8/SVneo', cell, migration, and, invasion, compared, with, controls])]). relacion([sujeto(['RNA', sequencing, of, 'GATA3', knockdown, cells, demonstrated, 96, differentially]), verbo([regulated]), complemento([genes, compared, with, controls])]). relacion([sujeto(['Genes', known, to, play, an, important, role, in, 'cell-cell', and, 'cell-extracellular', matrix, 'interactions,', cell, 'invasion,', and, placentation, were, 'identified,', including, 'CTGF,', 'CYR61,', 'ADAMTS12,', and, 'TIMP3', 'Our', results, demonstrate, estradiol, 'down-regulates', 'GATA3,', and]), verbo([decreased]), complemento(['GATA3', expression, leads, to, impaired, trophoblast, cell, migration, and, 'invasion,', likely, through, regulation, of, downstream, genes, important, in, placentation])]). relacion([sujeto(['These', results, are, consistent, with, clinical, data]), verbo([suggesting]), complemento([that, supraphysiologic, estrogen, levels, seen, in, 'IVF', pregnancies, may, play, an, important, role, in, attenuated, trophoblast, 'migration,', 'invasion,', and, impaired, placentation])]). relacion([sujeto(['GATA3', appears, to, be, an, important, regulator, of, placentation, and, may, play, a, role, in, impaired, outcomes]), verbo([associated]), complemento([with, fresh, 'IVF', cycles])]). relacion([sujeto(['Accumulating', studies]), verbo([have]), complemento([indicated, that, 'vitiligo,', especially, 'non-segmental', vitiligo, '(', 'NSV),', is, one, kind, of, autoimmune, diseases, and, 'CD4(+) T', cells, play, important, roles, in, the, pathogenesis])]). relacion([sujeto(['However,', there]), verbo([have]), complemento([been, very, limited, data, on, the, detailed, changes, of, each, of, the, 'CD4(+)', 'T', cell, subsets, in, periphery, in, active, 'NSV'])]). relacion([sujeto(['We']), verbo([found]), complemento([that, in, patients, with, 'NSV,', the, percentages, and, absolute, numbers, of, circulating, 'Th1', and, 'Th17', were, both, significantly, higher, than, those, of, healthy, 'controls,', while, the, percentages, of, 'Th2', and, 'Tregs', and, absolute, numbers, showed, no, significant, difference, compared, to, healthy, controls])]). relacion([sujeto(['Compared', with, healthy, 'controls,', the, expression, level, of, 'IL-17A', was, significantly]), verbo([increased]), complemento([in, serum, of, patients, with, 'NSV,', while, the, productions, of, 'IFN-γ,', 'IL-4,', 'TGF-β', had, no, significant, change])]). relacion([sujeto(['These', data]), verbo([suggested]), complemento([that, in, circulating, 'CD4(+) T', cell, 'subsets,', 'Th1', and, 'Th17', played, the, major, role, in, cellular, immunity, in, the, progression, of, vitiligo])]). relacion([sujeto(['The', immune, lever, in, circulation, was, inclined, to, effector, 'CD4(+) T', cells, not, suppressor, 'CD4(+) T', cells, that, may, result, in, the]), verbo([loss]), complemento([of, 'self-tolerance', to, melanocytes])]). relacion([sujeto(['The', 'AA', genotype, was]), verbo([associated]), complemento([with, shorter, disease, free, survival, '(', 'DFS)', in, univariate, '(', p, =])]). relacion([sujeto([28, ')', ',']), verbo([increased]), complemento([incidence, of, relapse, '(', p, =])]). relacion([sujeto(['The', 'AA', genotype, is]), verbo([associated]), complemento([with, shorter, 'DSF,', increased, incidence, of, relapse, and, poor, prognosis, in, pediatric, 'ALL'])]). relacion([sujeto(['Early-life', 'wheezing-associated', infections, with, rhinovirus, '(', 'RV)']), verbo([have]), complemento([been, associated, with, asthma, development, in, children])]). relacion([sujeto(['We']), verbo([have]), complemento([shown, that, 'RV', infection, of, six, 'day-old', mice, induces, mucous, metaplasia, and, airways, hyperresponsiveness, which, is, dependent, on, 'IL-13,', 'IL-25', and, type, 2, innate, lymphoid, cells, '(', 'ILC2s)'])]). relacion([sujeto(['Infection', of, immature, mice, fails, to]), verbo([induce]), complemento([lung, 'IFN-γ', 'expression,', in, contrast, to, mature, 8, 'week-old', mice, with, a, robust, 'IFN-γ', 'response,', consistent, with, the, notion, that, deficient, 'IFN-γ', production, in, immature, mice, permits, 'RV-induced', type, 2, immune, responses])]). relacion([sujeto(['We']), verbo([found]), complemento(['that,', compared, to, untreated, 'RV-infected', immature, 'mice,', 'IFN-γ', treatment, attenuated, 'RV-induced', 'IL-13', and, 'Muc5ac', mRNA, expression, and, mucous, metaplasia])]). relacion([sujeto(['We', conclude, 'that,', in, immature, 'mice,', 'IFN-γ']), verbo([inhibits]), complemento(['ILC2', expansion, and, 'IL-13', expression, in, vivo, and, ex, 'vivo,', thereby, attenuating, 'RV-induced', mucous, metaplasia])]). relacion([sujeto(['Despite', the, fact, that, accessory, spleen, '(', also, known, as, supernumerary, 'spleen,', 'splenunculus,', or, 'splenule)', can, be]), verbo([found]), complemento([in, 10, -, 30, '%', of, patients, undergoing, 'autopsies,', metastatic, disease, occurring, in, this, organ, has, been, barely, reported])]). relacion([sujeto(['A', case, of, lobular, breast, carcinoma, metastatic, to, the, spleen, and, accessory, spleen]), verbo([found]), complemento([incidentally, at, therapeutic, splenectomy, for, severe, anemia, and, thrombocytopenia, is, described])]). relacion([sujeto(['This', case, demonstrates, that, metastatic, carcinoma, can, be, 'encountered,', although, 'rarely,', in, accessory, spleens, and, that, cytokeratin, stain, should, be, performed, in, sections, of, spleens, 'and/or', accessory, spleens, excised, from, cancer, patients, in, which, the, presence, of, malignant, epithelial, cells, is, not]), verbo([recognized]), complemento([on, routine, sections])]). relacion([sujeto(['We']), verbo([find]), complemento([that, 'CCND3', expression, levels, do, not, correlate, with, 'amplification,', while, increased, 'GATA3', expression, in, mutant, 'GATA3', cancers, suggests, 'GATA3', is, an, oncogene])]). relacion([sujeto(['In', luminal, cases, the, total, number, of, 'substitutions,', irrespective, of, 'type,']), verbo([associates]), complemento([with, cell, cycle, gene, expression, and, adverse, 'outcome,', whereas, the, number, of, mutations, of, signatures, 3, and, 13, associates, with, 'immune-response', specific, gene, 'expression,', increased, numbers, of, 'tumour-infiltrating', lymphocytes, and, better, outcome])]). relacion([sujeto(['Thus,', while, earlier]), verbo([reports]), complemento([imply, that, the, sheer, number, of, somatic, aberrations, could, trigger, an, 'immune-response,', our, data, suggests, that, substitutions, of, a, particular, type, are, more, effective, in, doing, so, than, others])]). relacion([sujeto(['While', its, effects, in, later, stages, of, 'T', cell, differentiation, are, well, 'recognized,', the, role, of, 'GATA3', in, the, generation, of, early, 'T', cell, precursors, '(', 'ETP)']), verbo([has]), complemento([only, recently, been, explored])]). relacion([sujeto(['As', aberrant, 'GATA3', mRNA, expression]), verbo([has]), complemento([been, linked, to, 'cancerogenesis,', we, investigated, the, role, of, 'GATA3', in, early, 'T', cell, precursor, acute, lymphoblastic, leukemia, '(', 'ETP-ALL)'])]). relacion([sujeto(['Gene', expression, profiles, '(', 'Affymetrix', 'Human', genome, 'U133', 'Plus', 2.0, ')', of, an, independent, cohort, of, adult, 'T-ALL', '(', n, =, 83, ')', were, used, to, identify, 'ETP-ALL', and, investigate, 'GATA3(low)', and, 'GATA3(high)']), verbo([expressing]), complemento(['T-ALL', patients])]). relacion([sujeto(['Hypomethylating', agents]), verbo([induced]), complemento([reversal, of, 'GATA3', 'silencing,', and, gene, expression, profiling, revealed, downregulation, of, hematopoietic, stem, cell, genes, and, upregulation, of, 'T', cell, differentiation])]). relacion([sujeto(['The', 'Database', for, 'Annotation,', 'Visualization', and, 'Integrated', 'Discovery', '(', 'DAVID)', was, used, for, the, functional, enrichment, analysis, of, overlapping, genes, between, the]), verbo([target]), complemento([genes, and, differential, expression, genes, '(', 'DEGs)'])]). relacion([sujeto(['A', total, of, 46, ',', 487, peaks, were, identified, for, 'GATA3', and, out, of, 'which,', 3256, ones, were]), verbo([found]), complemento([to, located, at, -, 3000, &, 'nbsp;~ 0 bp', from, the, transcription, start, sites, '(', 'TSS)', of, their, nearby, gene])]). relacion([sujeto(['The', combined, analysis, of, 'ChIP-Seq', and, gene, expression, dataset, showed, 'GATA3']), verbo([act]), complemento([as, a, repressor, in, breast, cancer])]). relacion([sujeto(['Gene', 'Ontology', '(', 'GO)', terms, and, 'Kyoto', 'Encyclopedia', of, 'Genes', and, 'Genomes', '(', 'KEGG)', pathways, related, to, cancer, progression, and, gene, regulation, were]), verbo([found]), complemento([to, be, enriched, in, those, overlaps])]). relacion([sujeto([were]), verbo([found]), complemento([to, directly, interact, with, large, number, of, 'genes,', which, might, indicate, their, important, roles, in, the, progression, of, breast, cancer])]). relacion([sujeto(['Here,', we]), verbo([have]), complemento([shown, that, 'WAS', patients, and, mice, deficient, in, 'WAS', protein, '(', 'WASP)', frequently, develop, 'IgE-mediated', reactions, to, common, food, allergens])]). relacion([sujeto(['WASP-deficient', animals, displayed, an, 'adjuvant-free', 'IgE-sensitization', to, chow, antigens, that, was, most, pronounced, for, wheat, and]), verbo([soy]), complemento([and, occurred, under, specific, 'pathogen-free', as, well, as, 'germ-free', housing, conditions])]). relacion([sujeto(['Conditional', deletion, of, 'Was', in, 'FOXP3+', 'Tregs', resulted, in, more, severe, 'Th2-type', intestinal, inflammation, than, that, observed, in, mice, with, global, 'WASP', 'deficiency,', indicating, that, allergic, responses, to, food, allergens, are, dependent, upon]), verbo([loss]), complemento([of, 'WASP', expression, in, this, immune, compartment])]). relacion([sujeto(['Loss', of, 'WASP', was, phenotypically]), verbo([associated]), complemento([with, increased, 'GATA3', expression, in, effector, memory, 'FOXP3+', 'Tregs,', but, not, in, 'naive-like', 'FOXP3+', 'Tregs,', an, effect, that, occurred, independently, of, increased, 'IL-4', signaling])]). relacion([sujeto(['Our', results]), verbo([reveal]), complemento([a, 'Treg-specific', role, for, 'WASP', that, is, required, for, prevention, of, 'Th2', effector, cell, differentiation, and, allergic, sensitization, to, dietary, antigens])]). relacion([sujeto(['Nonurothelial', carcinoma]), verbo([has]), complemento([not, been, reported, to, be, immunoreactive, for, uroplakin, 'II'])]). relacion([sujeto(['GATA3', is, a, transcription, factor, that]), verbo([regulates]), complemento(['T-cell', production, of, cytokines])]). relacion([sujeto(['Colitis', was]), verbo([induced]), complemento([by, administration, of, oxazolone, or, 2, ',', 4, ',', 6, -, trinitrobenzenesulfonic, acid, to, control, 'mice,', mice, with, 'T-cell-specific', deletion, of, 'GATA3,', and, mice, with, deletion, of, tumor, necrosis, factor, receptor, '(', 'TNFR)', 1, and, 'TNFR2', '(', 'TNFR', double, 'knockouts);', some, mice, were, given, a, 'GATA3-specific', 'DNAzyme', '(', 'hgd40)', or, a, control, 'DNAzyme', via, intrarectal, 'administration,', or, systemic, injections, of, an, antibody, to, 'TNF', before, or, during, sensitization, and, challenge, phase, of, colitis, induction])]). relacion([sujeto(['We', observed]), verbo([increased]), complemento([expression, of, 'GATA3', by, lamina, propria, 'T', cells, from, mice, with, colitis, compared, with, controls])]). relacion([sujeto(['The', 'DNAzyme', hgd40]), verbo([inhibited]), complemento([expression, of, 'GATA3', messenger, 'RNA', by, unstimulated, and, stimulated, 'T', 'cells,', and, distributed, throughout, the, inflamed, colons, of, mice, with, colitis])]). relacion([sujeto(['Mice', given, hgd40, did, not, develop, colitis, after, administration, of, oxazolone, or, 2, ',', 4, ',', 6, -, trinitrobenzenesulfonic, 'acid;', lamina, propria, cells, from, these, mice]), verbo([expressed]), complemento([lower, levels, of, 'IL6,', 'IL9,', and, 'IL13', than, cells, from, mice, given, the, control, 'DNAzyme'])]). relacion([sujeto(['Levels', of, 'GATA3', are]), verbo([increased]), complemento([in, patients, with, 'UC', and, correlate, with, production, of, inflammatory, cytokines, in, mice, and, humans])]). relacion([sujeto(['A', 'DNAzyme', that]), verbo([prevents]), complemento([expression, of, 'GATA3', reduces, colitis, in, 'mice,', independently, of, 'TNF,', and, reduces, levels, of, cytokines, in, the, colon])]). relacion([sujeto(['GATA3']), verbo([has]), complemento([been, reported, as, a, specific, urothelial, marker, among, organs, in, the, pelvic, 'region,', and, has, been, classified, as, highly, sensitive, and, specific, for, urothelial, and, breast, carcinomas])]). relacion([sujeto(['All', cases, showed]), verbo([nuclear]), complemento([expression, of, 'GATA3'])]). relacion([sujeto(['GATA3', was, positive, in, all, extramammary, 'Paget', disease, cases, tested, '(', 13, 'cases),', and, it]), verbo([has]), complemento([no, value, for, differentiating, between, primary, and, secondary, vulvar, 'Paget', disease, from, the, urological, tract])]). relacion([sujeto(['HER2', amplification, might]), verbo([confer]), complemento([an, aggressive, and, invasive, pattern, in, primary, vulvar, 'Paget', 'disease,', as, both, amplified, cases, showed, an, invasive, pattern])]). relacion([sujeto(['Here,', mice, were, ovariectomized, and, then, 2, weeks, later, treated, with, 'MOG', antigen, to]), verbo([induce]), complemento(['EAE'])]). relacion([sujeto(['The', results, demonstrated, that, estrogen]), verbo([inhibited]), complemento([development, of, 'EAE'])]). relacion([sujeto(['High', and, medium, dose, of, estrogen]), verbo([increased]), complemento(['TH2', and, 'Treg', cell, production, of, interleukin, '(', 'IL)-4,', 'IL-10,', and, transforming, growth, factor, '(', 'TGF)-β,', but, concurrently, resulted, in, a, significant, reduction, in, production, of, interferon, '(', 'IFN)-γ,', 'IL-17,', and, 'IL-6'])]). relacion([sujeto(['Flow', cytometry, revealed, there, were, also, significant]), verbo([decreases]), complemento([in, the, percentages, of, 'TH1', and, 'TH17', 'cells,', as, well, as, significant, increase, in, percentages, of, 'Treg', and, 'TH2', cells, in, the, spleen, and, lymph, nodes])]). relacion([sujeto(['Real-time', 'PCR', results, indicated, that, 'high-', and, 'medium-dose', estrogen, treatments, reduced, 'T-bet', and, 'ROR-γt', factor, 'expression,', but]), verbo([enhanced]), complemento(['Foxp3', and, 'GATA3', expression])]). relacion([sujeto(['Global', pathway, analysis, of, the, transcriptome, revealed, 110, differentially]), verbo([expressed]), complemento(['immune-related', 'genes,', such, 'as,', 'complement,', 'MHCII,', chemokine, 'receptors,', defensins, and, 'cytokines,', at, birth])]). relacion([sujeto(['The', signaling, molecules, '(', 'LAX1,', 'BLK)', and, transcription, factors, '(', 'GATA3,', 'FOXP3)', are]), verbo([expressed]), complemento([at, high, levels])]). relacion([sujeto(['Unlike', 'adults,', 'IGKC', expression, is, high, in, the, neonates, where, 'IGKV12', is, preferentially]), verbo([expressed]), complemento([at, birth])]). relacion([sujeto([4, is, preferentially]), verbo([expressed]), complemento([in, 'B', cells, at, birth])]). relacion([sujeto(['Both', 'IGHM', and, 'IGHD', are]), verbo([expressed]), complemento([at, birth, and, 'IGHM', achieves, adult, levels, by, day, 7])]). relacion([sujeto(['We']), verbo([recruited]), complemento([96, 'subjects,', including, 23, healthy, 'volunteers,', 25, stable, allergic, 'asthmatics,', 21, mild, allergic, asthmatics, and, 27, moderate, allergic, 'asthmatics,', from, the, 'Affiliated', 'Hospital', of, 'Guilin', 'Medical', 'University'])]). relacion([sujeto(['Levels', of, 'ANP', signaling, in, serum, were, significantly]), verbo([increased]), complemento([with, the, severity, of, allergic, 'asthma,', suggesting, a, close, relation, with, the, pathogenesis, of, 'asthma;', 'ANP', signaling, may, play, a, role, in, the, pathogenesis, of, allergic, asthma, through, inducing, the, 'Th2-type', immune, response])]). relacion([sujeto(['目的:观察不同程度过敏性哮喘患者外周血心房钠尿肽(atrial', natriuretic, 'peptide,ANP)信号的变化,探讨其与哮喘程度的关系及ANP信号参与哮喘发病的可能机制。方法:共收集桂林医学院附属医院96例患者外周血标本,其中正常组23例、过敏性哮喘稳定组25例、轻度急性发作组21例、中度急性发作组27例。ELISA检测血清ANP及IFN-γ,IL-4的含量,RT-PCR及Western印迹分别检测利钠肽受体A(natriuretic', peptide, receptor, 'A,NPRA)及T盒21转录因子(T-box', 21, transcription, 'factor,T-bet),GATA结合蛋白3(GATA3']), verbo([binding]), complemento([protein, 3, ',GATA3)的mRNA与蛋白表达变化。', '结果:哮喘轻度发作组外周血ANP水平及单个核细胞(peripheral', blood, mononuclear, 'cell,PBMC)中NPRA的mRNA及蛋白表达水平均高于稳定组(P<0'])]). relacion([sujeto(['Vascular', endothelial, cell, growth, factor, '(', 'VEGF)', plays, a, pivotal, role, in]), verbo([promoting]), complemento([neovascularization])]). relacion([sujeto(['VEGF', gene, expression, in, vascular, endothelial, cells, in, normal, tissues, is]), verbo([maintained]), complemento([at, low, levels, but, becomes, highly, 'up-regulated', in, a, variety, of, disease, settings, including, cancers])]). relacion([sujeto(['We']), verbo([report]), complemento([here, that, 'VEGF', production, in, mouse, endothelial, cell, line, bEnd])]). relacion([sujeto([3, can, be]), verbo([inhibited]), complemento([by, 'TNFSF15', via, 'microRNA-29b', '(', 'miR-29b)', that, targets, the, 3, '\'', -, 'UTR', of, 'VEGF', transcript])]). relacion([sujeto(['Blocking', 'TNFSF15', activity, by, using, either, siRNA, against, the, 'TNFSF15', receptor, known, as, death, 'domain-containing', 'receptor-3', '(', 'DR3;', 'TNFRSF25),', or, a, neutralizing, antibody, 4, -, 3, 'H', against, 'TNFSF15,']), verbo([led]), complemento([to, inhibition, of, 'miR-29b', expression, and, reinvigoration, of, 'VEGF', production])]). relacion([sujeto(['In', 'addition,', we]), verbo([found]), complemento([that, 'TNFSF15', activated, the, 'JNK', signaling, pathway, as, well, as, the, transcription, factor, 'GATA3,', resulting, in, enhanced, 'miR-29b', production])]). relacion([sujeto(['Treatment', of, the, cells, either, with, 'SP600125,', an, inhibitor, of, 'JNK,', or, with, 'JNK', 'siRNA,']), verbo([led]), complemento([to, eradication, of, 'TNFSF15-induced', 'GATA3', expression])]). relacion([sujeto(['Moreover,', 'GATA3', siRNA]), verbo([suppressed]), complemento(['TNFSF15-induced', 'miR-29b', expression])]). relacion([sujeto(['These', findings]), verbo([suggest]), complemento([that, 'VEGF', gene, expression, can, be, suppressed, by, 'TNFSF15-stimulated', activation, of, the, 'JNK-GATA3', signaling, pathway, which, gives, rise, to, 'up-regulation', of, 'miR-29b'])]). relacion([sujeto(['Using', lentiviral, transfection, to]), verbo([induce]), complemento([stable, 'GATA3', knockdown, in, a, 'PTCL', cell, 'line,', we, observed, that, 'GATA-3', knockdown, in, 'Hut78', cells, decreased, levels, of, 'IL4,', 'IL5,', 'IL13', and, 'VEGF', mRNA, and, reduced, the, number, of, 'co-cultured', 'U937', cells, that, differentiated, towards, the, 'M2', phenotype])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, high, 'GATA3', expression, is, a, predictor, of, a, poor, prognosis, in, 'PTCL,', and, that, 'T', lymphoma, cells, promote, 'M2-type', macrophage, differentiation, through, a, 'GATA3-dependent', mechanism])]). relacion([sujeto(['Patterns', of, somatic, mutations, in, cancer, genes]), verbo([provide]), complemento([information, about, their, functional, role, in, 'tumourigenesis,', and, thus, indicate, their, potential, for, therapeutic, exploitation])]). relacion([sujeto(['For', 'instance,', 'TP53']), verbo([has]), complemento([been, simultaneously, associated, with, tumour, suppressing, and, promoting, activities])]). relacion([sujeto(['We', identify, two, functional, classes, of, frameshift, mutations, that, are]), verbo([associated]), complemento([with, distinct, expression, profiles, in, 'tumours,', differential, 'disease-free', patient, survival, and, 'gain-', and, 'loss-of-function', activities, in, a, cell, line, model])]). relacion([sujeto(['Furthermore,', we]), verbo([find]), complemento([an, estrogen, 'receptor-independent', synthetic, lethal, interaction, between, a, 'GATA3', frameshift, mutant, with, an, extended, 'C-terminus', and, the, histone, methyltransferases, 'G9A', and, 'GLP,', indicating, perturbed, epigenetic, regulation])]). relacion([sujeto(['Our', findings]), verbo([reveal]), complemento([important, insights, into, mutant, 'GATA3', function, and, breast, 'cancer,', provide, the, first, potential, therapeutic, strategy, and, suggest, that, dual, tumour, suppressive, and, oncogenic, activities, are, more, widespread, than, previously, appreciated])]). relacion([sujeto(['GATA3,', a, lineage, 'specifier,', controls, lymphoid, cell, differentiation, and, its, function, in, 'T', cell, commitment, and, development]), verbo([has]), complemento([been, extensively, studied])]). relacion([sujeto(['GATA3']), verbo([promotes]), complemento(['T', cell, specification, by, repressing, 'B', cell, potential, in, pro, 'T', cells, and, decreased, 'GATA3', expression, is, essential, for, early, 'B', cell, commitment])]). relacion([sujeto(['Inherited', genetic, variation, in, 'GATA3']), verbo([has]), complemento([been, associated, with, lymphoma, susceptibility])]). relacion([sujeto(['However,', it, remains, elusive, how, the]), verbo([loss]), complemento([of, function, of, 'GATA3', promotes, 'B', cell, development, and, induces, 'B', cell, lymphomas])]). relacion([sujeto(['In', this, 'study,', we]), verbo([found]), complemento([that, haploid, loss, of, 'Gata3', by, heterozygous, germline, deletion, increased, 'B', cell, populations, in, the, bone, marrow, '(', 'BM)', and, 'spleen,', and, decreased, 'CD4', 'T', cell, populations, in, the, 'thymus,', confirming, that, 'Gata3', promotes, 'T', and, suppresses, 'B', cell, development])]). relacion([sujeto(['We', discovered, that, haploid]), verbo([loss]), complemento([of, 'Gata3', reduced, thymocyte, proliferation, with, induction, of, p18Ink4c, '(', 'p18),', an, inhibitor, of, 'CDK4', and, 'CDK6,', but, enhanced, 'B', cell, proliferation, in, the, 'BM', and, spleen, independent, of, p18])]). relacion([sujeto(['Loss', of, p18, partially, restored, 'Gata3', deficient, thymocyte, 'proliferation,', but, further]), verbo([stimulated]), complemento(['Gata3', deficient, 'B', cell, proliferation, in, the, 'BM', and, spleen])]). relacion([sujeto(['Furthermore,', we, discovered, that, haploid]), verbo([loss]), complemento([of, 'Gata3', in, p18, deficient, mice, led, to, the, development, of, 'B', cell, lymphomas, that, were, capable, of, rapidly, regenerating, tumors, when, transplanted, into, immunocompromised, mice])]). relacion([sujeto(['These', results, indicate, that, 'Gata3', deficiency]), verbo([promotes]), complemento(['B', cell, differentiation, and, 'proliferation,', and, cooperates, with, p18, loss, to, induce, 'B', cell, lymphomas])]). relacion([sujeto(['This', 'study,', for, the, first, 'time,']), verbo([reveals]), complemento([that, 'Gata3', is, a, tumor, suppressor, specifically, in, 'B', cell, lymphomagenesis])]). relacion([sujeto(['Mesenchymal', stem, cells, '(', 'MSCs)']), verbo([have]), complemento([strong, immunomodulatory, 'properties,', however, these, properties, may, show, some, differences, according, to, the, tissue, type, of, their, isolate])]). relacion([sujeto(['We']), verbo([found]), complemento([that, the, 'CD4(+)-Tbet(+)', '(', 'Th1)', and, 'CD4(+)-Gata3(+)', '(', 'Th2)', cells, were, suppressed, by, the, 'hDP-MSCs,', but, the, 'CD4(+)-Stat3(+)', '(', 'Th17)', and, 'CD4(+)-CD25(+)-FoxP3(+)', '(', 'Treg)', cells, were, stimulated])]). relacion([sujeto(['The', expressions, of, 'T', cell, specific, cytokines, interferon, gamma, '(', 'IFN-g),', interleukin, '(', 'IL)-4', and, 'IL-17a', 'decreased,', but, 'IL-10', and, transforming, growth, factor, 'beta-1', '(', 'TGF-b1)']), verbo([increased]), complemento([with, the, 'hDP-MSCs'])]). relacion([sujeto(['The', expressions, of, 'indoleamine-pyrrole', 2, ',', 3, -, dioxygenase, '(', 'IDO),', prostaglandin, 'E2', '(', 'PGE2),', soluble, human, leukocyte, antigen, 'G', '(', 'sHLA-G)', derived, from, 'hDP-MSCs', slightly, 'increased,', but, hepatocyte, growth, factor, '(', 'HGF)', significantly]), verbo([increased]), complemento([in, the, 'co-culture', groups])]). relacion([sujeto(['According', to, our, 'findings,', the, 'hDP-MSCs', can]), verbo([suppress]), complemento([the, 'Th1', and, 'Th2', subsets, but, stimulate, the, 'Th17', and, 'Treg', subsets])]). relacion([sujeto(['The', 'Stat3', expression, of, 'Th17', cells, may]), verbo([have]), complemento([been, stimulated, by, the, 'HGF,', and, thus, the, 'pro-inflammatory', 'Th17', cells, may, have, altered, into, the, immunosuppressive, regulatory, 'Th17', cells])]). relacion([sujeto(['ILC2s', were, then]), verbo([stimulated]), complemento([with, phorbol, 12, -, myristate, 13, -, acetate, plus, 'ionomycin,', 'IL-25', plus, 'IL-33', '(', 'IL-25/IL-33),', or, a, mixture, of, 'Toll-like', receptor, ligands, to, evaluate, their, ability, to, produce, 'cytokines,', express, 'CD154,', and, induce, 'IgE', production, by, autologous, 'B cells'])]). relacion([sujeto(['ILC2s']), verbo([expressed]), complemento(['GATA-3,', retinoic, acid, orphan, receptor, '(', 'RORC)', 2, ',', and, 'RORα;', were, able, to, produce, 'IL-5,', 'IL-13,', and, 'IL-4;', 'and,', 'accordingly,', were, characterized, by, demethylation, of, 'IL4,', 'IL13,', 'IL5,', 'GATA3,', and, 'RORC2,', whereas, the, 'IFNG,', 'IFNG', 'promoter,', and, 'TBX21', regions, of, interest, were, methylated])]). relacion([sujeto(['ILC2s']), verbo([expressed]), complemento(['TLR1,', 'TLR4,', and, 'TLR6,', and, 'TLR', stimulation, induced, 'IL-5', and, 'IL-13', production])]). relacion([sujeto(['Moreover,', 'ILC2s']), verbo([expressed]), complemento(['CD154', in, response, to, phorbol, 12, -, myristate, 13, -, acetate, plus, 'ionomycin,', 'IL-25/IL-33,', or, a, mixture, of, 'TLR', ligands])]). relacion([sujeto(['Stimulated', 'ILC2s', also]), verbo([induced]), complemento(['IgM,', 'IgG,', 'IgA,', and, 'IgE', production, by, 'B cells'])]). relacion([sujeto(['Finally,', circulating, 'ILC2s', from, atopic, patients, were, not, different, in, numbers, and, frequency, but]), verbo([expressed]), complemento([higher, 'IL-4', levels, than, those, from, nonatopic, subjects])]). relacion([sujeto(['This', study]), verbo([provides]), complemento([the, first, evidence, that, human, 'ILC2s', can, express, 'CD154', and, stimulate, the, production, of, 'IgE', by, 'B', lymphocytes, through, 'IL-25/IL-33', stimulation, or, 'TLR', triggering])]). relacion([sujeto(['In', the, horse, model, of, spontaneous, recurrent, 'uveitis,', intraocular, lymphoid, follicle, formation, is, highly, 'characteristic,', and]), verbo([found]), complemento([in, all, stages, and, scores, of, 'disease,', but, in, depth, analyses, of, immunologic, features, of, these, structures, are, lacking, to, date])]). relacion([sujeto(['Paraffin-embedded', eye, sections, of, cases, with, equine, spontaneous, recurrent, uveitis, '(', 'ERU)', were, characterized, with, immunohistochemistry, to]), verbo([gain]), complemento([insight, into, the, 'distribution,', 'localization,', and, signaling, of, immune, cells, in, intraocular, tertiary, lymphoid, tissues])]). relacion([sujeto(['Almost', all, cells, coexpressed, 'CD166,', a, molecule]), verbo([associated]), complemento([with, activation, and, transmigration, of, 'T', cells, into, inflamed, tissues])]). relacion([sujeto(['A', high, expression, of, the]), verbo([phosphorylated]), complemento([signal, transducers, and, activators, of, transcription, '(', 'STAT)', proteins, 1, and, 5, were, found, at, the, margin, of, the, structures])]). relacion([sujeto(['Suppression', of, 'ELK3', in, 'MDA-MB-231', cells]), verbo([led]), complemento([to, transdifferentiation, from, an, invasive, mesenchymal, phenotype, to, a, 'non-invasive', epithelial, phenotype, both, in, vitro, and, in, vivo])]). relacion([sujeto(['Also,', suppression, of, 'GATA3']), verbo([led]), complemento([to, the, restoration, of, migration, and, invasion])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, the, 'ELK3-GATA3', axis, is, a, major, pathway, that, promotes, metastasis, of, 'MDA-MB-231', cells])]). relacion([sujeto(['Proper', cell, models, for, breast, cancer, primary, tumors]), verbo([have]), complemento([long, been, the, focal, point, in, the, 'cancer\'s', research])]). relacion([sujeto(['These', important, drug]), verbo([targets]), complemento([in, breast, 'cancer,', 'ESR1,', 'PGR,', 'HER2,', 'EGFR', and, 'AR', have, a, high, similarity, in, mRNA, and, protein, variation, in, both, tumors, and, cell, lines])]). relacion([sujeto(['GATA3', and, 'RP56KB1', are, two, promising, drug]), verbo([targets]), complemento([for, breast, cancer])]). relacion([sujeto(['A', total, score, developed, from, the, four, correlations, among, four, molecular, profiles]), verbo([suggests]), complemento([that, cell, 'lines,', 'BT483,', 'T47D', and, 'MDAMB453', have, the, highest, similarity, with, tumors])]). relacion([sujeto(['Invariant', natural, killer, 'T', cells, '(', 'iNKTs)', are, important, innate, immune, cells, which, get]), verbo([involved]), complemento([in, various, immune, responses, in, both, mice, and, humans])]). relacion([sujeto(['Next,', we, investigated, the, impacts, of, 'CH1b', and, 'CH2b', on, 'proliferation,', cytokines, 'production,', 'cytotoxicity,', and, the]), verbo([associated]), complemento([signaling, pathways, in, iNKT, cells])]). relacion([sujeto(['Finally,', we]), verbo([found]), complemento([that, 'CH2b', could, significantly, promote, the, activated, iNKTs, 'proliferation,', increase, the, production, of, 'Th2', 'cytokines,', and, induce, 'Th0', differentiation, into, 'Th2', subset, via, 'GATA', 3, signaling, pathway])]). relacion([sujeto(['Besides,', 'CH2b', could, markedly]), verbo([enhance]), complemento([the, cytotoxic, ability, of, the, activated, iNKTs])]). relacion([sujeto(['Several', natural, compounds, exhibit, strong, capacity, for]), verbo([decreasing]), complemento([triglyceride, 'accumulation,', enhancing, lipolysis, and, inducing, apoptosis])]). relacion([sujeto(['The', present, study]), verbo([reports]), complemento([the, 'anti-adipogenic', effects, of, 'Silybum', marianum, '(', 'SL),', 'Citrus', aurantium, '(', 'CA),', 'Taraxacum', officinale, '(', 'TO),', resveratrol, '(', 'RE),', 'Curcuma', longa, '(', 'CU),', caffeine, '(', 'CF),', oleuropein, '(', 'OL)', and, docosahexaenoic, acid, '(', 'DHA)', in, reducing, differentiation, and, increasing, lipolysis, and, apoptosis])]). relacion([sujeto(['The', percentage, of, apoptosis]), verbo([induced]), complemento([by, 'TO', extract, in, 'P10', and, 'P20', cells, was, significantly, higher, than, that, induced, by, all, other, compounds, and, in, 'CTRL', cells])]). relacion([sujeto(['On', the, 'contrary,', the, treatment, of, 'A7', cells, with, 'OL,', 'CA', and, 'TO', compounds, significantly]), verbo([increased]), complemento([cell, lipolysis])]). relacion([sujeto(['The', addition, of, 'CF', in, differentiating, 'P20', 'pre-adipocytes', significantly]), verbo([increased]), complemento([the, expression, of, genes, involved, in, inhibition, of, 'adipogenesis,', such, as, 'GATA2,', 'GATA3,', 'WNT1,', 'WNT3A,', 'SFRP5,', and, 'DLK1'])]). relacion([sujeto(['Genes']), verbo([involved]), complemento([in, promoting, adipogenesis, such, as, 'CCND1,', 'CEBPB', and, 'SREBF1', were, significantly, 'down-regulated', by, the, treatment])]). relacion([sujeto(['The', screening, of, bioactive, compounds, for, 'anti-adipogenic', effects, showed, that, in, differentiating, cells, 'TO', extract, was, the, most, effective, in]), verbo([inducing]), complemento([apoptosis, and, 'CF', and, 'DHA', extracts, were, more, efficient, in, inhibition, of, differentiation, and, in, induction, of, cell, lipolysis])]). relacion([sujeto(['Sarcomatoid', dedifferentiation]), verbo([has]), complemento([been, previously, described, in, a, few, 'cases,', but, other, forms, of, dedifferentiation, have, not, been, reported])]). relacion([sujeto([small, cell, 'carcinoma)', is]), verbo([associated]), complemento([with, 'HPV', 'infection,', typically, 'HPV', 18])]). relacion([sujeto(['We', describe, a, case, of, mesonephric, adenocarcinoma, of, the, uterine, cervix]), verbo([associated]), complemento([with, an, 'HPV-negative', 'high-grade', neuroendocrine, carcinoma, at, the, morphologic, and, immunophenotypic, 'level,', for, which, we, performed, targeted, massively, parallel, sequencing, analysis, of, the, 2, elements])]). relacion([sujeto(['Our', data]), verbo([suggest]), complemento([a, clonal, origin, of, the, 2, components, of, this, rare, 'entity,', rather, than, a, collision, tumor])]). relacion([sujeto(['Analysis', of, cytokine, transcripts]), verbo([has]), complemento([shown, that, inflammatory, 'Th1/Th17', 'T', cells, are, associated, with, development, of, paucibacillary, pathology, and, 'Th2', cytokines, are, correlated, with, multibacillary, disease])]). relacion([sujeto(['Sequence', variations, of, the, transcription, factors]), verbo([have]), complemento([also, been, implicated, in, the, distinct, disease, forms, of, human, mycobacterial, and, gastrointestinal, inflammatory, diseases])]). relacion([sujeto(['Low', levels, of, 'GATA3', in, multibacillary, sheep, failed, to, confirm, that, multibacillary, paratuberculosis, is]), verbo([caused]), complemento([simply, by, a, 'Th2', immune, response])]). relacion([sujeto(['Increased', 'RORAv1', levels, in, paucibacillary, tissue]), verbo([suggests]), complemento([a, role, for, 'RORα', in, 'Th17', development, in, 'sheep;', while, elevated, levels, of, 'RORAv4', hints, that, this, variant, might, inhibit, 'RORα', function, and, depress, 'Th17', development, in, multibacillary, sheep])]). relacion([sujeto(['Through', analysis, with, the, chromatin, immunoprecipitation, 'assay,', we]), verbo([found]), complemento([that, 'HBV', infection, promotes, the, expression, of, transcription, factors, 'GATA-2', and, 'GATA-3,', which, specifically, suppressed, 'MICA/B', expression, by, directly, binding, to, the, promoter, region, of, 'MICA/B'])]). relacion([sujeto(['HBx', 'protein,']), verbo([acting]), complemento([as, a, 'co-regulator,', forms, a, tripolymer, with, 'GATA2', and, 'GATA3,', thus, promotes, the, 'GATA-2', or, 'GATA-3-mediated', of, 'MICA/B', suppression])]). relacion([sujeto(['HBc', protein]), verbo([inhibits]), complemento(['MICA/B', expression, via, directly, binding, to, the, 'CpG', island, in, the, 'MICA/B', promoter])]). relacion([sujeto(['Thus,', our, study, identified, the, novel, role, of, transcription, factors, 'GATA-2', and, 'GATA-3', in]), verbo([suppressing]), complemento(['MICA/B', expression, and, clarified, the, mechanisms, of, 'HBx', and, 'HBc', in, downregulation, of, 'MICA/B', expression])]). relacion([sujeto(['These', findings]), verbo([provide]), complemento([novel, mechanisms, for, the, contribution, of, 'HBV', to, hepatoma, cells, escape, from, 'NK', cell, surveillance])]). relacion([sujeto(['Differential', prognostic, roles, of, 'Androgen', 'Receptor', '(', 'AR)']), verbo([have]), complemento([been, proposed, in, breast, cancer, '(', 'BC)', depending, on, tumour, oestrogen, receptor, '(', 'ER)', status])]). relacion([sujeto(['Nuclear', 'AR', 'IHC', expression, was, significantly]), verbo([associated]), complemento([with, features, of, good, prognosis, including, older, 'age,', smaller, tumour, 'size,', lower, grade, and, lobular, histology, particularly, in, the, 'ER-positive', tumours])]). relacion([sujeto(['AR', was]), verbo([associated]), complemento([with, 'ER-related', markers, 'GATA3,', 'FOXa1,', 'RERG', and, 'BEX1'])]). relacion([sujeto(['AR', 'Overexpression', was]), verbo([associated]), complemento([with, longer, survival, '(', 'p < 0'])]). relacion([sujeto(['Similar', associations, were]), verbo([maintained]), complemento([in, 'ER+', tumours, in, univariate, and, multivariate, analysis, '(', 'p < 0'])]). relacion([sujeto(['In', the, external, validation, 'cohorts,', 'AR', gene, expression, data, were]), verbo([associated]), complemento([with, improved, 'patients\'', outcome, '(', 'p < 0'])]). relacion([sujeto(['AR', is, not, only, an, independent, prognostic, factor, in, 'ER-positive', luminal, 'BC', but, is, also]), verbo([expressed]), complemento([in, 'ER-negative', tumours])]). relacion([sujeto(['AR', could]), verbo([act]), complemento([as, a, molecular, target, in, patients, with, 'ER-positive', disease, predicting, response, to, adjuvant, therapy])]). relacion([sujeto(['Effective', immunosuppression, strategies, and, genetically, modified, animals]), verbo([have]), complemento([been, used, to, prevent, hyperacute, and, acute, xenograft, 'rejection;', 'however,', the, underlying, mechanisms, remain, unknown])]). relacion([sujeto(['Recipients', treated, with, immunosuppressive, agents, without, grafting, showed, significant, downregulation, of, 'CCL5,', 'CCR4,', 'CCR6,', 'CD4,', 'CD40LG,', 'CXCR3,', 'FASLG,', 'CXCR3,', 'FOXP3,', 'GATA3,', 'IGNG,', 'L10,', 'IL23A,', 'TRAF6,', 'MAPK8,', 'MIF,', 'STAT4,', 'TBX21,', 'TLR3,', 'TLR7,', and, 'TYK2', and, upregulation, of, 'IFNGR1;', 'thus,', genes]), verbo([involved]), complemento([in, protection, against, viral, and, bacterial, infection, were, 'downregulated,', confirming, the, risk, of, infection])]). relacion([sujeto(['Notably,', 'C3-level', control, resulted, in, xenograft, failure, within, 2, days, because, of, a, 7, -, to, 11, -, fold]), verbo([increase]), complemento([in, all, xenotransplanted, models])]). relacion([sujeto(['We', observed, at, least, 5, -, fold, upregulation, in, recipients, transplanted, with, islets, grafts, from, single, '(', 'MX1)', or, double, '(', 'C3,', 'CCR8,', 'IL6,', 'IL13,', 'IRF6,', 'CXCL10,', and, 'MX1)', 'GalT-KO', pigs, after, 77, 'days;', single, 'GalT-KO', incurred, early]), verbo([losses]), complemento([owing, to, immune, attacks])]). relacion([sujeto(['Our', results]), verbo([suggest]), complemento([that, this, 'novel,', 'simple,', 'non-invasive,', and, 'time-efficient', procedure, '(', requiring, only, 1.5, ml, 'blood)', for, evaluating, graft, 'success,', minimizing, immune, 'rejection,', and, blocking, infection])]). relacion([sujeto(['Combined', 'RNA-seq', transcriptomic, profiling, and, 'Reduced', 'Representation', 'Bisulfite', 'Sequencing', identified, 193, significantly, differentially]), verbo([expressed]), complemento([genes, and, 760, differentially, methylated, regions, '(', 'DMRs),', between, 'CD4(+)', 'T', cells, from, 'M'])]). relacion([sujeto([196, 'DMRs', were, located, within, 10, kb, of, annotated, 'genes,', including, 'GATA3', and, 'RORC,', both, of, which, encode, transcription, factors, that]), verbo([promote]), complemento(['TH2', and, 'TH17', 'T', helper, cell, subsets, respectively])]). relacion([sujeto(['Gene-specific', 'DNA', methylation, and, gene, expression, levels, for, the, 'TNFRSF4', and, 'Interferon-γ', genes, were, significantly, negatively, correlated]), verbo([suggesting]), complemento([a, regulatory, relationship])]). relacion([sujeto(['Pathway', analysis, of, 'DMRs', identified, enrichment, of, genes]), verbo([involved]), complemento([in, the, 'anti-proliferative', 'TGF-β', signaling, pathway, and, 'TGFB1', expression, was, significantly, increased, in, peripheral, blood, leukocytes, from, 'TB-infected', cattle])]). relacion([sujeto(['This', first, analysis, of, the, bovine, 'CD4(+)', 'T', cell, methylome]), verbo([suggests]), complemento([that, 'DNA', methylation, directly, contributes, to, a, distinct, gene, expression, signature, in, 'CD4(+)', 'T', cells, from, cattle, infected, with, 'M'])]). relacion([sujeto(['Much', research, effort]), verbo([has]), complemento([been, focused, on, investigating, new, compounds, derived, from, 'low-cost', 'sources,', such, as, natural, 'products,', for, treating, leishmaniasis])]). relacion([sujeto(['The', aim, of, the, present, study, is, to, investigate, the, possible, 'mechanism(s)', that]), verbo([mediate]), complemento([this, leishmanicidal, activity])]). relacion([sujeto(['The', extensive, oxidative, stress]), verbo([found]), complemento([in, 'oleuropein-treated', mice, was, obviated, by, the, upregulation, of, the, 'host\'s', antioxidant, enzyme, '(', 'mGCLC)', and, the, simultaneous, downregulation, of, the, corresponding, enzyme, of, the, parasite, '(', 'LdGCLC)'])]). relacion([sujeto(['The', ability, of, 'Oleuropein', to]), verbo([promote]), complemento([a, 'Th1', type, immune, response, in, 'L'])]). relacion([sujeto(['Understanding', the, role, of, chromatin, organization, and, regulation, in, 'HSC', homeostasis, may]), verbo([provide]), complemento([important, insights, into, 'HSC', development])]). relacion([sujeto(['Bromodomain-', and, 'PHD', 'finger-containing', protein, 1, '(', 'BRPF1)', is, a, multivalent, chromatin, regulator, that, possesses, 4, 'nucleosome-binding', domains, and]), verbo([activates]), complemento([3, lysine, acetyltransferases, '(', 'KAT6A,', 'KAT6B,', and, 'KAT7),', suggesting, that, this, protein, has, the, potential, to, stimulate, crosstalk, between, different, chromatin, modifications])]). relacion([sujeto(['Furthermore,', 'BRPF1', was]), verbo([required]), complemento([for, acetylation, of, histone, 'H3', at, lysine, 23, ',', a, highly, abundant, but, not, 'well-characterized', epigenetic, mark])]). relacion([sujeto(['They', can, be, cultured, in, 'vitro,']), verbo([retaining]), complemento([the, ability, to, 'self-renew', and, to, differentiate, into, all, subtypes, of, the, trophoblast, 'lineage,', equivalent, to, the, in, vivo, stem, cell, population, giving, rise, to, the, fetal, portion, of, the, placenta])]). relacion([sujeto(['The']), verbo([induced]), complemento([trophoblast, stem, cells, are, able, to, 'self-renew', and, are, almost, identical, to, blastocyst, derived, trophoblast, stem, cells, in, terms, of, 'morphology,', marker, gene, expression, and, methylation, pattern])]). relacion([sujeto(['The', functions, of, 'POU', class, 5, transcription, factor, 1, '(', 'Oct-4)', and, 'caudal-type', homeobox, 2, '(', 'Cdx2)', in, the, differentiation, of, the, murine, inner, cell, mass, '(', 'ICM)', and, trophectoderm, '(', 'TE)']), verbo([have]), complemento([been, described, in, detail])]). relacion([sujeto(['Gene', expression, analysis, revealed]), verbo([decreased]), complemento(['CDX2', and, fibroblast, growth, factor, 4, expression, in, 'OCT-4-downregulated', embryos])]). relacion([sujeto(['Gene', expression, analysis, revealed]), verbo([decreased]), complemento(['GATA3', expression, and, elevated, 'NANOG', expression, in, 'CDX2-downregulated', embryos])]). relacion([sujeto(['In', 'conclusion,', 'OCT-4', and, 'CDX2', are, essential, for, early, development, and, gene, expression]), verbo([involved]), complemento([in, differentiation, of, 'ICM', and, 'TE', lineages, in, bovine, embryos])]). relacion([sujeto(['The', pathologic, distinction, between, 'high-grade', prostate, adenocarcinoma, '(', 'PAC)']), verbo([involving]), complemento([the, urinary, bladder, and, 'high-grade', urothelial, carcinoma, '(', 'UC)', infiltrating, the, prostate, can, be, difficult])]). relacion([sujeto([1, ',', and, 'α-methylacyl', coenzyme, 'A', racemase, '[', 'AMACR])', and, urothelial, markers, '(', 'CK34βE12,', 'p63,', 'thrombomodulin,', 'S100P,', and, 'GATA']), verbo([binding]), complemento([protein, 3, '[', 'GATA3])', was, performed, using, tissue, microarrays, from, each, tumor])]). relacion([sujeto([2015, '\'', s, insights, to, asthma, inception, included, how, the, intestinal, microbiome, affects, asthma, expression, with, the, identification, of, specific, gastrointestinal, bacterial, taxa, in, early, infancy]), verbo([associated]), complemento([with, less, asthma, 'risk,', possibly, by, promoting, regulatory, immune, development, at, a, critical, early, age])]). relacion([sujeto(['The', relevance, of, epigenetic, mechanisms, in]), verbo([regulating]), complemento(['asthma-related', gene, expression, was, strengthened])]). relacion([sujeto(['Predicting', and]), verbo([preventing]), complemento([exacerbations, throughout, life, might, help, to, reduce, progressive, lung, function, decrease, and, disease, severity, in, adulthood])]). relacion([sujeto(['Although', allergy]), verbo([has]), complemento([long, been, linked, to, asthma, 'exacerbations,', a, mechanism, through, which, 'IgE', impairs, rhinovirus, immunity, and, underlies, asthma, exacerbations, was, demonstrated, and, improved, by, 'anti-IgE', therapy, '(', 'omalizumab)'])]). relacion([sujeto(['Several', genes]), verbo([have]), complemento([been, recognized, to, be, associated, with, 'non-surgical', hypoparathyroidism])]). relacion([sujeto(['This', study, was, designed, to, screen, gene, mutation, in, 'adult-onset', hypoparathyroidism, in, 'Chinese', through, the]), verbo([targeted]), complemento(['next-generation', sequencing, '(', 'NGS)'])]). relacion([sujeto(['We']), verbo([recruited]), complemento([17, patients, with, 'adult-onset', hypoparathyroidism, who, were, regularly, followed, or, newly, diagnosed, at, our, centre, during, the, past, one, year])]). relacion([sujeto(['Although', the, molecular, mechanisms, governing, 'Tfh', cell, differentiation, from, naive, 'T', cells]), verbo([have]), complemento([been, widely, 'described,', much, less, is, known, about, the, regulation, of, cytokine, secretion, by, mouse, 'Tfh-2', cells])]). relacion([sujeto(['Our', results, demonstrate, that, priming, of, 'Th', cells, by, 'IL-6-deficient', 'antigen-presenting', dendritic, cells, preferentially]), verbo([leads]), complemento([to, accumulation, of, a, subset, of, 'Tfh', cells, characterized, by, high, expression, of, 'GATA3', and, 'IL-4,', associated, with, reduced, production, of, 'IL-21'])]). relacion([sujeto(['STAT3-deficient', 'Tfh', cells, also, overexpress, 'GATA3,']), verbo([suggesting]), complemento([that, early, 'IL-6/STAT3', signaling, during, 'Tfh', cell, development, inhibits, the, expression, of, a, set, of, genes, associated, with, the, 'Th2', differentiation, program])]). relacion([sujeto(['In', terms, of, the, changes, of, the, 'expression,', 'PgR,', 'Ki67,', and, 'FOXA1', expression, significantly]), verbo([decreased]), complemento([after, 'NAE', '(', 'P < 0'])]). relacion([sujeto(['The', integration, of, multiple, profiling, data, and, the, construction, of, a, transcriptional, regulatory, network, may]), verbo([provide]), complemento([additional, insights, into, the, molecular, mechanisms, of, hepatocellular, carcinoma, '(', 'HCC)'])]). relacion([sujeto(['An', integrated, analysis, of, eight, eligible, gene, expression, profiles, of, 'HCC']), verbo([led]), complemento([to, 1, ',', 835, 'DEGs'])]). relacion([sujeto(['Consistent', with, the, fact, that, the, cell, cycle, is, closely, related, to, various, 'tumors,', the, functional, annotation, revealed, that, genes]), verbo([involved]), complemento([in, the, cell, cycle, were, significantly, enriched])]). relacion([sujeto(['The', transcriptional, regulatory, network, can]), verbo([provide]), complemento([additional, information, that, is, valuable, in, understanding, the, underlying, molecular, mechanism, in, hepatic, tumorigenesis])]). relacion([sujeto(['The', 'BCG', vaccine]), verbo([induces]), complemento([a, 'Th1', 'phenotype,', which, is, essential, for, protection, against, 'Mycobacterium', tuberculosis])]). relacion([sujeto(['However,', the, effects, of, 'BCG', vaccination, over, time, on, the, 'T', helper, subpopulation, and, the, microRNAs]), verbo([involved]), complemento([in, adulthood, have, not, been, studied])]). relacion([sujeto(['We', observed, a]), verbo([decrease]), complemento([in, the, expression, levels, of, 'T-BET,', 'GATA3', and, 'FOXP3', at, 2, months, and, 'miR-146a,', 'miR-326', and, 'miR-155', at, 6, months, after, receiving, the, vaccine])]). relacion([sujeto(['In', the, 'supernatant,', the, production, of, 'IL-17', was]), verbo([increased]), complemento([after, 6, 'months,', with, both, stimuli])]). relacion([sujeto(['In', 'contrast,', 'IL-10,', 'TNF-α', and, 'IFN-γ']), verbo([increased]), complemento([at, 2, months])]). relacion([sujeto(['In', the, 'serum,', high, levels, of, 'IL-10', were]), verbo([found]), complemento([after, 2, months, compared, to, time, 0, and, 6, months])]). relacion([sujeto(['The', production, of, multifunctional, cells, that]), verbo([expressed]), complemento([the, cytokine, profiles, 'CD4+TNF-α+IFN-γ-IL-10-,', 'CD4+TNF-α+IL-1IFN-γ-,', 'CD4+IL-10+IFN-γ-TNF-α-', and, 'CD4+IL-17+IFN-γ-', predominantly, increased, after, 2, months, with, and, without, the, stimulus])]). relacion([sujeto(['This', study, is, the, first, to, demonstrate, roles, for, 'microRNAs,', transcription, factors, and, cytokines, in, the, 'T', helper, differentiation, lineage, and, to, describe, the, possible, mechanism, by, which, their, expression, is]), verbo([modulated]), complemento([by, the, presence, of, the, 'BCG', vaccine, in, adulthood])]). relacion([sujeto(['In', 'conclusion,', our, results]), verbo([suggest]), complemento([that, the, 'BCG', vaccine, induces, a, modulation, in, transcription, factors, and, miRNAs, with, high, production, of, multifunctional, cells, 'CD4+TNF-α+IL-10+IFN-γ-'])]). relacion([sujeto(['In', this, study, we, show, that, special, 'AT-rich']), verbo([binding]), complemento([protein, 1, '(', 'SATB1),', a, 'T', 'lineage-enriched', chromatin, organizer, and, 'regulator,', is, induced, in, response, to, 'TCR', signaling, during, early, thymocyte, development])]). relacion([sujeto(['We', also, demonstrate, that, 'GATA3,', the, key, transcriptional, regulator, of, αβ, 'T', cells, positively]), verbo([regulates]), complemento(['SATB1', expression, in, thymocytes, suggesting, an, important, role, for, 'SATB1', during, 'T', cell, development])]). relacion([sujeto(['Mice', model, of, 'CIA', was]), verbo([induced]), complemento([by, chicken, collagen, 'II', and, arthritis, index, was, assessed])]). relacion([sujeto(['The', paw, swelling, and, arthritis, index, were]), verbo([decreased]), complemento([and, body, weight, was, increased, in, the, high, dose, of, dioscin, group, compared, to, the, model, group, '(', 'P<0'])]). relacion([sujeto(['Additionally,', 'p-STAT4', expression, was, 'decreased,', and, both, 'p-STAT6', and, 'GATA3', expression, was]), verbo([increased]), complemento([in, the, dioscin, group, than, that, in, the, model, group, '(', 'P<0'])]). relacion([sujeto(['Dioscin', might]), verbo([have]), complemento([some, therapeutic, effects, on, 'CIA', through, regulating, the, proportion, of, 'Th1/Th2', 'cells,', which, could, reduce, the, expression, of, 'p-STAT4,', increase, the, expression, of, 'p-STAT6', and, 'GATA3', in, the, synovial, tissue])]). relacion([sujeto(['Prostate', carcinoma]), verbo([has]), complemento([been, reported, as, the, most, frequent, primary, to, metastasize, to, the, 'breast;', 'however,', the, reverse, has, not, been, previously, reported])]). relacion([sujeto(['The']), verbo([induced]), complemento([expression, of, the, transcription, factors, neurogenin1, '(', 'Neurog1)', or, neuronal, differentiation, 1, '(', 'NeuroD1)', has, previously, been, shown, to, initiate, neuronal, differentiation, in, embryonic, stem, cells, '(', 'ESC)'])]). relacion([sujeto(['Human', 'BMSCs', were, transduced, with, lentivirus]), verbo([expressing]), complemento(['NeuroD1', or, 'Neuorg1'])]). relacion([sujeto(['Transduced', cells, were, then, treated, with, small, molecules, that]), verbo([enhanced]), complemento([neuronal, differentiation])]). relacion([sujeto(['Using', quantitative, reverse, transcription, 'PCR,', the, 'up-regulation', of, transcription, factors]), verbo([expressed]), complemento([by, developing, primary, auditory, 'neurons,', such, as, 'BRN3a', '(', 'POU4F1)', and, 'GATA3,', was, quantified, after, induction, of, 'Neurog-1', expression])]). relacion([sujeto(['In', 'addition,', the, expression, of, the, receptor, 'NTRK2', was]), verbo([induced]), complemento([by, treatment, with, its, specific, ligand, 'BDNF'])]). relacion([sujeto(['NeuroD1', seemed, not, sufficient, to]), verbo([induce]), complemento([and, maintain, neuronal, differentiation])]). relacion([sujeto(['However,', it, seems, not, sufficient, to]), verbo([maintain]), complemento([the, glutamatergic, spiral, ganglion, 'neuron-like', phenotype])]). relacion([sujeto(['Clear', cell, urothelial, carcinoma, '(', 'CCUC)', is, a, rare, variant, of, urothelial, carcinoma, '(', 'UC)', and, its, clinical, significance]), verbo([has]), complemento([not, been, well, elucidated])]). relacion([sujeto(['This', variant, is]), verbo([associated]), complemento([with, rapid, progression, to, muscle, invasion, and, 'metastasis,', with, an, aggressive, clinical, course])]). relacion([sujeto(['The', balance, between, 'Th17', cells, and, regulatory, 'T', '(', 'Treg)', cells]), verbo([has]), complemento([been, shown, to, play, an, important, role, in, the, development, of, rheumatoid, arthritis, '(', 'RA)'])]). relacion([sujeto(['Recent', studies]), verbo([have]), complemento([shown, that, treatment, with, abatacept, '(', 'ABT)', or, tocilizumab, '(', 'TCZ)', affects, 'Th17', and, 'Treg', cell, populations])]). relacion([sujeto(['Although', not, unanimously, 'accepted,', several]), verbo([reports]), complemento([have, shown, that, 'Treg', cells, are, decreased, by, 'ABT', and, increased, by, 'TCZ,', and, that, 'Th17', cells, are, decreased, by, 'TCZ'])]). relacion([sujeto(['The', relative, expression, levels, were]), verbo([expressed]), complemento([as, the, ratios, of, two, genes, '(', 'T-bet/GATA3,', 'Foxp3/GATA3,', 'Foxp3/T-bet,', 'Foxp3/Ror-γt,', 'Ror-γt/T-bet,', 'Ror-γt/GATA3),', and, the, changes, in, these, ratios, with, treatment, were, determined])]). relacion([sujeto(['The', 'Foxp3/Ror-γt', ratio, was]), verbo([decreased]), complemento([after, 'ABT', therapy, '(', 0.67, ±, 0.16, at, 24, &, 'nbsp;weeks,', 'P', =, 0.0034, ')', but, was, increased, after, 'TCZ', therapy, '(', 2.0, ±, 1.03, at, 24, &, 'nbsp;weeks,', 'P', =, 0.0013, ')'])]). relacion([sujeto(['In', 'addition,', the, 'Ror-γt/GATA3', ratio, was]), verbo([decreased]), complemento([after, 'TCZ', therapy, '(', 0.78, ±, 0.37, at, 24, &, 'nbsp;weeks,', 'P', =, 0.0008, ')'])]). relacion([sujeto(['Data', integration]), verbo([has]), complemento([become, a, useful, strategy, for, uncovering, new, insights, into, complex, biological, networks])]). relacion([sujeto(['The', network, illustrates, that, important, and, 'well-known', 'TFs', for, 'Th2', cell, differentiation, are, positively]), verbo([regulated]), complemento([by, 'STAT6', and, act, either, as, activators, for, 'Th2', cells, '(', e])]). relacion([sujeto(['Moreover,', our, approach]), verbo([reveals]), complemento([11, 'TFs', '(', e])]). relacion([sujeto(['This', fact, together, with, the, observed, enrichment, of, asthma, risk, genes, among, those]), verbo([regulated]), complemento([by, 'STAT6', underlines, the, potential, value, of, the, data, integration, strategy, used, here])]). relacion([sujeto(['Construction', of, the, transcriptional, regulatory, network, can]), verbo([provide]), complemento([additional, clues, on, the, regulatory, mechanisms, and, therapeutic, applications, in, gastric, cancer])]). relacion([sujeto(['Furthermore,', a, total, of, 70, differentially]), verbo([expressed]), complemento(['TFs', were, identified, and, the, transcriptional, regulatory, network, was, 'constructed,', which, consisted, of, 566, 'TF-target', interactions])]). relacion([sujeto(['The', top, ten, 'TFs']), verbo([regulating]), complemento([most, downstream, target, genes, were, 'BRCA1,', 'ARID3A,', 'EHF,', 'SOX10,', 'ZNF263,', 'FOXL1,', 'FEV,', 'GATA3,', 'FOXC1,', and, 'FOXD1'])]). relacion([sujeto(['Most', of, them, were]), verbo([involved]), complemento([in, the, carcinogenesis, of, gastric, cancer])]). relacion([sujeto(['Human', 'T-cell', leukemia, virus, type, 1, '(', 'HTLV-1)']), verbo([causes]), complemento([adult, 'T-cell', 'leukemia-lymphoma', '(', 'ATL)', and, other, inflammatory, diseases, in, infected, individuals])]). relacion([sujeto(['Expression', of, the, chemokine, receptor, 'CCR4', on, 'ATL', cells, and, 'HTLV-1-infected', cells]), verbo([suggested]), complemento([the, hypothesis, that, 'CCR4', may, mediate, features, of, 'ATL', and, inflammatory, diseases, caused, by, 'HTLV-1'])]). relacion([sujeto(['In', this, 'study,', we, show, that, the, constitutively]), verbo([expressed]), complemento(['HTLV-1', bZIP, factor, '(', 'HBZ)', encoded, by, 'HTLV-1', is, responsible, for, inducing, 'CCR4', and, its, ability, to, promote, 'T-cell', proliferation, and, migration])]). relacion([sujeto(['Ectopic', expression, of, 'HBZ', was, sufficient, to]), verbo([stimulate]), complemento([expression, of, 'CCR4', in, human, and, mouse, 'T', cells])]). relacion([sujeto(['Conversely,', 'HBZ', silencing, in, 'ATL', cell, lines, was, sufficient, to]), verbo([inhibit]), complemento(['CCR4', expression])]). relacion([sujeto(['Mechanistic', investigations, showed, that, 'HBZ']), verbo([induced]), complemento(['GATA3', expression, in, 'CD4(+)', 'T', 'cells,', thereby, activating, transcription, from, the, 'CCR4', promoter])]). relacion([sujeto(['Migration', of, 'CD4(+)', 'T', cells, in, 'HBZ-Tg', mice, was]), verbo([inhibited]), complemento([by, treatment, with, a, 'CCR4', antagonist])]). relacion([sujeto(['Proliferating', '(', 'Ki67(+))', 'CD4(+)', 'T', cells, were]), verbo([found]), complemento([to, express, high, levels, of, 'CCR4', and, 'CD103'])]). relacion([sujeto(['Further,', 'CD4(+)', 'T-cell', proliferation, in, 'HBZ-Tg', mice, was]), verbo([enhanced]), complemento([by, coordinate, treatment, with, the, 'CCR4', ligands, 'CCL17', and, 22, and, with, the, 'CD103', ligand, 'E-cadherin'])]). relacion([sujeto(['Consistent', with, this, 'finding,', we]), verbo([found]), complemento([that, 'ATL', cells, in, clinical, skin, lesions, were, frequently, positive, for, 'CCR4,', 'CD103,', and, 'Ki67'])]). relacion([sujeto(['Taken', 'together,', our, results, show, how, 'HBZ']), verbo([activates]), complemento(['CCR4', expression, on, 'T', cells, to, augment, their, migration, and, 'proliferation,', two, phenomena, linked, to, 'HTLV-1', pathogenesis])]). relacion([sujeto(['The', advent, of, 'Omics', technologies]), verbo([has]), complemento([been, key, to, the, molecular, subclassification, of, urothelial, bladder, cancer])]). relacion([sujeto(['Several', groups]), verbo([have]), complemento([used, different, strategies, to, this, 'aim,', with, partially, overlapping, findings])]). relacion([sujeto(['An', additional, tumor, subgroup, with, urothelial, differentiation, features, was]), verbo([recognized]), complemento([whose, optimal, molecular, definition, is, required])]). relacion([sujeto(['GATA', transcription, factors, are, essential, in, mammalian, cell, lineage, determination, and]), verbo([have]), complemento([a, critical, role, in, cancer, development])]). relacion([sujeto(['In', cultured, prostate, cancer, 'cells,', 'GATA2', coordinates, with, androgen, receptor, '(', 'AR)', to]), verbo([regulate]), complemento([gene, transcription])]). relacion([sujeto(['Ablation', of, single, 'GATA', gene, had, marginal, effect, on, prostate, morphology, and, 'AR']), verbo([target]), complemento([gene, 'expression,', likely, due, to, their, genetic, compensation])]). relacion([sujeto(['Double', 'KO', mice, exhibited, 'PIN', 'III', to, 'IV', 'lesions,', but]), verbo([decreased]), complemento([prostate, to, body, weight, 'ratio,', altered, 'AR', target, gene, 'expression,', and, expansion, of, 'p63-positive', basal, cells])]). relacion([sujeto(['However,', deletion, of, 'GATA2', and, 'GATA3', did, not, reduce, the, mRNA, or, protein, levels, of, 'AR', or, 'FoxA1,', indicating, that, 'GATA', factors, are, not]), verbo([required]), complemento([for, 'AR', or, 'FoxA1', expression, in, adult, prostate])]). relacion([sujeto(['Together,', our, results, indicate, that, 'GATA2', and, 'GATA3', are, essential, for, adult, murine, prostate, function, and, in, vivo, 'AR', 'signaling,', and, the, lack, of, the, 'GATA', factor, expression, in, the, 'VP']), verbo([suggests]), complemento([a, fundamental, difference, between, 'VP', and, other, prostatic, lobes])]). relacion([sujeto(['An', important, step, towards, personalizing, cancer, treatment, is, to, integrate, heterogeneous, evidences, to, catalog, mutational, hotspots, that, are, biologically, and, therapeutically, relevant, and, thus, represent, where]), verbo([targeted]), complemento([therapy, would, likely, be, beneficial])]). relacion([sujeto(['We']), verbo([found]), complemento([that, the, hotspot, mutations, nominated, by, our, approach, were, significantly, more, conserved, than, 'non-hotspot', mutations, in, the, corresponding, cancer, genes])]). relacion([sujeto(['We', also, examined, the, biological, significance, and, pharmacogenomics, properties, of, these, hotspot, mutations, using, data, in, the, 'Cancer', 'Genome', 'Atlas', '(', 'TCGA)', and, the, 'Cancer', 'Cell-Line', 'Encyclopedia', '(', 'CCLE),', and]), verbo([found]), complemento([that, 53, hotspot, mutations, are, independently, associated, with, diverse, functional, evidences, in, 1, ')', mRNA, and, protein, 'expression,', 2, ')', pathway, 'activity,', or, 3, ')', drug, sensitivity, and, 82, were, highly, enriched, in, specific, tumor, types])]). relacion([sujeto(['We', illustrated, the, common, and, distinct, mutational, signatures, of, hotspot, mutations, among, different, tumor, types, and, investigated, their, variable, functional, relevance, under, different, 'contexts,', which, could, potentially, serve, as, a, resource, for, explicitly, selecting]), verbo([targets]), complemento([for, 'diagnosis,', drug, 'development,', and, patient, management])]). relacion([sujeto(['As', a, distinct, 'M2-polarized', 'population,', 'tumour-associated', macrophages, '(', 'TAMs)']), verbo([promote]), complemento([tumorigenesis, owing, to, their, 'pro-angiogenic', and, 'immune-suppressive', functions, in, tumour, microenvironment])]). relacion([sujeto(['In', the, present, 'study,', we]), verbo([found]), complemento([that, the, 'microRNA-720', '(', 'miR-720)', was, 'down-regulated', in, 'TAMs', isolated, from, breast, carcinomas, and, 'M2-polarization', macrophages])]). relacion([sujeto(['Overexpression', of, 'miR-720', attenuated, 'M2', phenotype, expression, and, thus]), verbo([inhibited]), complemento(['M2', polarization])]). relacion([sujeto(['We', further, identified, 'GATA']), verbo([binding]), complemento([protein, 3, '(', 'GATA3),', a, transcriptional, factor, that, plays, an, important, role, in, 'M2', macrophage, 'polarization,', was, the, downstream, target, of, 'miR-720', 'Ectopic', expression, of, 'GATA3', restored, the, 'M2', phenotype, in, 'miR-720', overexpressed, macrophages])]). relacion([sujeto(['Importantly,', overexpression, of, 'miR-720']), verbo([inhibited]), complemento(['pro-migration', behaviour, and, phagocytic, ability, of, 'M2-polarized', macrophages])]). relacion([sujeto(['Thus,', our, data]), verbo([suggest]), complemento([that, 'miR-720', plays, an, important, role, in, regulating, 'M2', macrophage, polarization, and, function])]). relacion([sujeto(['However,', the, pathogenesis, of, 'RCC']), verbo([has]), complemento([not, yet, been, fully, elucidated])]). relacion([sujeto(['To', interpret, the, pathogenesis, of, 'RCC', at, the, molecular, 'level,', gene, expression, data, and, 'bio-informatics', methods, were, used, to, identify, 'RCC']), verbo([associated]), complemento([genes])]). relacion([sujeto(['In', 'addition,', a, regulatory, network, was, constructed, using, the, known, regulatory, data, between, transcription, factors, '(', 'TFs)', and]), verbo([target]), complemento([genes, in, the, 'University', of, 'California', 'Santa', 'Cruz', '(', 'UCSC)', 'Genome', 'Browser', '(', 'http://genome'])]). relacion([sujeto(['The', regulatory, network, contained, 1, ',', 525, pairs, of, regulatory, associations, between, 126, 'TFs', and, 1, ',', 259]), verbo([target]), complemento([genes, and, these, genes, were, mainly, enriched, in, cancer, 'pathways,', 'ErbB', and, 'MAPK'])]). relacion([sujeto(['In', the, regulatory, 'network,', the, 10, most, strongly]), verbo([associated]), complemento(['TFs', were, 'FOXC1,', 'GATA3,', 'ESR1,', 'FOXL1,', 'PATZ1,', 'MYB,', 'STAT5A,', 'EGR2,', 'EGR3', and, 'PELP1'])]). relacion([sujeto(['GATA3,', 'ERG', and, 'MYB', serve, important, roles, in, 'RCC', while, 'FOXC1,', 'ESR1,', 'FOXL1,', 'PATZ1,', 'STAT5A', and, 'PELP1', may, be, potential, genes]), verbo([associated]), complemento([with, 'RCC'])]). relacion([sujeto(['MF/CTCL']), verbo([have]), complemento([increased, expression, of, thymocyte, 'selection-associated', 'HMG', box, protein, '(', 'TOX)'])]). relacion([sujeto(['Although', 'TOX']), verbo([has]), complemento([been, proposed, to, be, a, diagnostic, marker, for, 'MF,', further, validation, studies, are, needed])]). relacion([sujeto(['In', 'CTCL', 'cells,', 'GATA3', knockdown]), verbo([decreased]), complemento(['TOX', mRNA, and, protein, expression])]). relacion([sujeto(['TOX', expression, also]), verbo([decreased]), complemento([in, the, presence, of, 'CTCL', therapeutics])]). relacion([sujeto(['Moreover,', 'TOX', expression, was, evident, in, 'LPP,', indicating, it, may]), verbo([have]), complemento([a, previously, unappreciated, role, in, the, development, of, 'MF'])]). relacion([sujeto(['Finally,', our, data]), verbo([suggest]), complemento([that, 'GATA3', regulates, 'TOX,', revealing, insight, into, 'TOX', regulation])]). relacion([sujeto(['Elevated', systemic, 'IL-6', in, 'IR', individuals, was]), verbo([associated]), complemento([with, hyperplasia, of, adipose, 'tissue-derived', 'SVF', 'cells,', despite, higher, frequency, of, hypertrophied, adipocytes])]). relacion([sujeto(['Impaired', adipogenesis, in, 'IR', individuals, was, further]), verbo([associated]), complemento([with, increased, adipose, secretion, of, 'IL-6'])]). relacion([sujeto(['Understanding', the, molecular, mechanisms, underlying, reduced, adipogenic, capacity, in, 'IR', individuals, could, help]), verbo([target]), complemento([appropriate, therapeutic, strategies, aimed, at, those, at, greatest, risk, of, insulin, resistance, and, type, 2, diabetes, mellitus])]). relacion([sujeto(['Loss', of, the, 'SWI/SNF', chromatin, remodeling, complex]), verbo([has]), complemento([been, recently, implicated, in, the, pathogenesis, of, dedifferentiated, carcinomas, from, different, 'organs,', but, its, possible, role, in, undifferentiated, urothelial, carcinoma, '(', 'UC)', has, not, been, studied, to, date])]). relacion([sujeto(['The', undifferentiated, component, almost, always]), verbo([expressed]), complemento(['pan-cytokeratin', 'AE1/AE3', '(', 13, /, 14, ')', and, variably, vimentin, '(', 8, /, 14, ')', and, 'GATA3', '(', 9, /, 14, ')'])]). relacion([sujeto(['Complete']), verbo([loss]), complemento([of, at, least, one, 'SWI/SNF', subunit, limited, to, the, undifferentiated, component, was, detected, in, 10, /, 14, cases, '(', 71, &, 'nbsp;%)'])]). relacion([sujeto(['Our', results, are, in, line, with, recent, studies]), verbo([reporting]), complemento([involvement, of, the, 'SWI/SNF', complex, in, the, dedifferentiation, process, of, a, variety, of, epithelial, neoplasms, in, different, 'organs,', including, the, urinary, 'tract,', and, association, with, aggressive, clinical, course])]). relacion([sujeto(['GATA-3', is, a, transcription, factor]), verbo([involved]), complemento([in, human, tissue, growth, and, differentiation])]). relacion([sujeto(['GATA3', positivity, was]), verbo([associated]), complemento([with, 'ER', or, 'PR', positivity, in, 84, '%', of, cases])]). relacion([sujeto(['Hearing', impairment, most, often]), verbo([involves]), complemento([loss, of, sensory, hair, cells, and, auditory, neurons])]). relacion([sujeto(['As', this]), verbo([loss]), complemento([is, permanent, in, 'humans,', a, cell, therapy, approach, has, been, suggested, to, replace, damaged, cells])]). relacion([sujeto(['In', this, 'study,', we]), verbo([have]), complemento([investigated, the, effects, of, three, small, molecules, 'SB431542,', 'ISX9', and, 'Metformin', to, direct, differentiation, of, 'lt-NES', cells, into, sensory, neurons])]). relacion([sujeto(['Exposure', of, 'lt-NES', cells, to, 'Metformin', or, 'SB431542', did, not]), verbo([induce]), complemento([any, marked, induction, of, markers, for, sensory, neurons])]). relacion([sujeto(['However,', a, four, days, exposure, to, the, 'ISX9', small, molecule, resulted, in, reduced, expression, of, 'NeuroD1', mRNA, as, well, as]), verbo([enhanced]), complemento([mRNA, levels, of, 'GATA3,', a, marker, and, important, player, in, auditory, neuron, specification, and, development])]). relacion([sujeto(['Subsequent', culture, in, the, presence, of, the, neurotrophic, factors, 'BDNF', and, 'NT3', for, another, seven, days, yielded, a, further]), verbo([increase]), complemento([of, mRNA, expression, for, 'GATA3'])]). relacion([sujeto(['Lung', cancer, is, a]), verbo([leading]), complemento([cause, of, 'cancer-related', mortality, 'worldwide,', and, cigarette, smoking, is, the, major, environmental, hazard, for, its, development])]). relacion([sujeto(['Current', smoking, was, linked, to, a, 0.74, '%', to, 2.4, '%']), verbo([decrease]), complemento([of, 'DNA', methylation, compared, to, never, smoking, in, 11, 'loci,', and, all, but, one, showed, significant, associations, '(', 'FDR', &, 'lt;0'])]). relacion([sujeto(['In', 'conclusion,', our, study, demonstrates, the, impact, of, tobacco, smoking, on, 'DNA', methylation, of, lung, cancer, related, 'genes,', which, may, indicate, that, lung, cancer, susceptibility, genes, might, be]), verbo([regulated]), complemento([by, methylation, changes, in, response, to, smoking])]). relacion([sujeto(['In', 'addition,', the, transcription, 'factor,', 'T‑box 21', '(', 'T‑bet)', and, 'GATA']), verbo([binding]), complemento(['protein 3', '(', 'GATA‑3)', mRNA, expression, levels, were, investigated, in, the, peripheral, blood, mononuclear, cells, '(', 'PBMCs)', of, patients, with, 'CHB'])]). relacion([sujeto(['The', expression, levels, of, the, 'CD28', family, receptors, in, the, 'T cells', of, patients, with, 'CHB', demonstrated, distinct, characteristics, ',', for, example, levels, of, 'PD‑1', and, 'CTLA‑4', on, 'CD4', 'T', cells, and, 'ICOS,', 'PD‑1,', and, 'BTLA', on, 'CD8', 'T', cells, were]), verbo([increased]), complemento([in, cells, from, patients, with, 'CHB', compared, with, those, from, the, healthy, individuals])]). relacion([sujeto(['PD‑1', blockade, altered, the, expression, profiles, of, 'CD28', family, receptors, in, the, 'T cells', of, patients, with, 'CHB,', partly]), verbo([enhanced]), complemento(['T cell', function, and, increased, the, ratio, of, 'T‑bet/GATA‑3', mRNA, in, 'PBMCs'])]). relacion([sujeto(['Furthermore,', 'PD‑1', blockade]), verbo([has]), complemento([a, therapeutic, potential, that, may, be, enhanced, by, modulating, the, expression, of, 'co-stimulatory', 'and -inhibitory', receptors, of, the, 'CD28', family])]). relacion([sujeto(['The', 'IFNL3']), verbo([responder]), complemento([genotype, predicted, significantly, lower, white, blood, cells, '(', 'WBCs),', as, well, as, lower, absolute, numbers, of, 'monocytes,', neutrophils, and, lymphocytes, for, both, rs8099917, and, rs12979860])]). relacion([sujeto(['Taken', 'together,', these, data]), verbo([provide]), complemento([evidence, of, an, 'IFNL3', genotype, association, with, differences, in, 'monocyte,', 'T-', and, 'NK', cell, levels, in, the, peripheral, blood, of, patients, with, 'CHC'])]). relacion([sujeto(['Donepezil', '(', 'DNPZ)', is, a, drug, commonly, used, for, 'Alzheimer\'s', disease, '(', 'AD)', that, may, favour, a, 'T', helper, 2, phenotype]), verbo([leading]), complemento([to, increased, naturally, occurring, 'auto-antibodies', '(', 'NAb)', against, 'beta-amyloid', '(', 'Aβ)'])]). relacion([sujeto(['We', hypothesized, the, involvement, of, the, cholinergic, receptors, '[', 'α7-nicotnic', acetylcholine, receptor, '(', 'α7nAChR)]']), verbo([expressed]), complemento([on, peripheral, blood, mononuclear, cells, '(', 'PBMC)'])]). relacion([sujeto(['Donepezil']), verbo([increased]), complemento([in, vitro, the, expression, of, the, transcription, factor, 'GATA', binding, protein, 3, '(', 'GATA3)', through, 'α7nAChR,', because, prevented, by, the, specific, antagonist, methyllycaconitine])]). relacion([sujeto(['Ex', vivo, 'PBMC', α7nAChR, mRNA, expression, was]), verbo([increased]), complemento([in, both, 'AD', 'groups,', while, 'GATA3', expression, was, not])]). relacion([sujeto(['A', significant]), verbo([increase]), complemento([in, the, 'GATA3/interleukin', 5, promoter, association, was, found, in, 'DNPZ+', patients])]). relacion([sujeto(['Donepezil', might]), verbo([modulate]), complemento([a, 'T', helper, 2, bias, via, α7nAChR, leading, to, increased, expression, of, 'NAb'])]). relacion([sujeto(['Hydroxytyrosol']), verbo([has]), complemento([various, pharmacological, 'properties,', including, 'anti-oxidative', stress, and, 'anti-inflammatory', 'activities,', preventing, 'hyperglycemia,', insulin, 'resistance,', and, the, metabolic, syndrome])]). relacion([sujeto(['The', treatment, with, hydroxytyrosol, extract, significantly, '(', 'P', &, 'lt;', 0.001, ')']), verbo([increased]), complemento([apoptosis, in, 'P10', and, 'P20', cells, in, comparison, to, control, and, 'A7', 'cells;', significantly, '(', 'P', &, 'lt;', 0.001, ')', reduced, triglyceride, accumulation, in, 'P20', cells, compared, to, 'P10', and, control, 'cells;', and, significantly, '(', 'P', &, 'lt;', 0.001, ')', increased, lipolysis, in, 'P20', cells, in, comparison, to, control, cells, and, 'A7', mature, adipocytes])]). relacion([sujeto(['Hydroxytyrosol-treated', 'P20', cells, significantly, '(', 'P', &, 'lt;', 0.05, ')']), verbo([increased]), complemento([expression, of, genes, involved, in, inhibition, of, 'adipogenesis,', such, as, 'GATA2,', 'GATA3,', 'WNT3A,', 'SFRP5,', 'HES1,', and, 'SIRT1'])]). relacion([sujeto(['In', 'contrast,', genes]), verbo([involved]), complemento([in, promoting, adipogenesis, such, as, 'LEP,', 'FGF1,', 'CCND1,', and, 'SREBF1', were, significantly, 'down-regulated', by, hydroxytyrosol, treatment])]). relacion([sujeto(['These', data]), verbo([suggest]), complemento([that, hydroxytyrosol, promotes, lipolysis, and, apoptotic, activity, in, primary, human, visceral, 'pre-adipocytes', during, differentiation, and, does, not, affect, already, mature, adipocytes])]). relacion([sujeto(['Ten', genetic, abnormalities, were]), verbo([found]), complemento([to, be, statistically, associated, with, histologic, 'grade,', including, three, most, prevalent, cancer, driver, 'events,', 'TP53', and, 'PIK3CA', mutations, and, 'MYC', amplification])]). relacion([sujeto(['While', 'TP53', mutation, and, 'MYC', amplification, were, synergistic, in]), verbo([promoting]), complemento([tumor, 'progression,', 'PIK3CA', mutation, was, found, to, have, alleviated, the, oncogenic, effect, of, either, the, 'TP53', mutation, or, 'MYC', 'amplification,', and, was, associated, with, a, significant, reduction, in, mitotic, activity, in, 'TP53', mutated, 'and/or', 'MYC', amplified, breast, cancer])]). relacion([sujeto(['Furthermore,', we, discovered, that, different, types, of, genetic, abnormalities, '(', mutation, versus, 'amplification)', within, the, same, cancer, driver, gene, '(', 'PIK3CA', or, 'GATA3)', were]), verbo([associated]), complemento([with, opposite, histologic, changes, in, invasive, breast, cancer])]). relacion([sujeto(['In', 'conclusion,', our, study]), verbo([suggests]), complemento([that, histologic, grade, may, serve, as, a, biomarker, to, define, cancer, driving, genetic, events, in, vivo])]). relacion([sujeto(['WDR77', '(', 'WD', repeat, domain, 77, ')', is]), verbo([expressed]), complemento([during, earlier, lung, development, when, cells, are, rapidly, 'proliferating,', but, is, absent, from, adult, lung])]). relacion([sujeto(['The', 'WDR77', promoter, is, transactivated, by, 'E2F1,', 'E2F3,', 'GATA1', and, 'GATA6,', but]), verbo([suppressed]), complemento([by, 'E2F6,', 'GATA1', and, 'GATA3 in', prostate, cancer, 'PC3', cells])]). relacion([sujeto(['WDR77', expression, is]), verbo([associated]), complemento([with, 'E2F1,', 'E2F3,', 'GATA2', and, 'GATA6', occupancy, on, the, 'WDR77', 'gene,', 'whereas,', in, 'contrast,', 'E2F6,', 'GATA1', and, 'GATA3', occupancy, is, associated, with, the, loss, of, 'WDR77', expression, during, erythroid, maturation, and, lung, development])]). relacion([sujeto(['More', 'importantly,', the]), verbo([loss]), complemento([of, 'WDR77', expression, that, results, from, 'E2F', and, 'GATA', switches, is, required, for, cellular, differentiation, of, erythroid, and, lung, epithelial, cells])]). relacion([sujeto(['Altogether,', the, present, study]), verbo([provides]), complemento([a, novel, molecular, mechanism, by, which, 'WDR77', is, regulated, during, erythroid, and, lung, development, and, lung, tumorigenesis])]). relacion([sujeto(['Th2-eosinophil', immune, responses, are, well, known, for]), verbo([mediating]), complemento([host, defence, against, helminths])]). relacion([sujeto(['In', two, independent, models, of, 'arthritis,', 'Nippostrongylus', brasiliensis, infection]), verbo([leads]), complemento([to, 'Th2', and, eosinophil, accumulation, in, the, joints, associated, with, robust, inhibition, of, arthritis, and, protection, from, bone, loss])]). relacion([sujeto(['Furthermore,', we, show, that, eosinophils, play, a, central, role, in, the, modulation, of, arthritis, probably, through, the]), verbo([increase]), complemento([of, 'anti-inflammatory', macrophages, into, arthritic, joints])]). relacion([sujeto(['Although']), verbo([increasing]), complemento([evidence, demonstrated, that, deregulation, of, 'mircoRNA-503', '(', 'miRNA-503)', contributes, to, 'tumorigenesis,', little, is, known, about, the, biological, role, and, intrinsic, regulatory, mechanisms, of, 'miR-503', in, prostate, cancer, '(', 'PCa)'])]). relacion([sujeto(['In', present, 'study,', we]), verbo([found]), complemento([that, 'miR-503', was, significantly, downregulated, in, advanced, 'PCa', tissues, and, cell, lines])]). relacion([sujeto(['Downregulation', of, 'miR-503', was, strongly]), verbo([associated]), complemento([with, aggressive, 'clinical-pathological', features, and, poor, prognosis, in, 'PCa', patients])]). relacion([sujeto(['Ectopic', expression, of, 'miR-503', significantly]), verbo([inhibited]), complemento([tumor, cells, 'growth,', cell, migration, and, invasion, in, vitro, and, in, vivo])]). relacion([sujeto(['Mechanistic', studies, revealed, that, 'ZNF217', was, a, direct]), verbo([target]), complemento([downstream, target, of, 'miR-503'])]). relacion([sujeto(['Subsequently,', 'miR-503', further]), verbo([modulated]), complemento([the, activation, of, 'ZNF217-downstream', 'epithelial-mesenchymal', transition, '(', 'EMT)', genes])]). relacion([sujeto(['Besides,', we, also]), verbo([found]), complemento([that, 'GATA3', directly, increased, 'miR-503', expression, and, thus, decreased, 'ZNF217', 'expression,', indicating, the, involvement, of, 'GATA3/miR-503/ZNF217', signaling, in, 'EMT', process])]). relacion([sujeto(['Collectively,', our, results, demonstrated, that, 'GATA3-driven', expression, of, 'miR-503']), verbo([inhibits]), complemento(['PCa', progression, by, repressing, 'ZNF217', 'expression,', and, also, implicated, the, potential, application, of, 'miR-503', in, 'PCa', therapy])]). relacion([sujeto(['Heterozygous', germ, line, 'GATA2', mutations]), verbo([induce]), complemento(['GATA2-deficiency', 'syndrome,', characterized, by, 'monocytopenia,', a, predisposition, to, 'myelodysplasia/acute', myeloid, 'leukemia,', and, a, profoundly, reduced, 'DC', 'population,', which, is, associated, with, increased, susceptibility, to, viral, 'infections,', impaired, 'phagocytosis,', and, decreased, cytokine, production])]). relacion([sujeto(['GATA2', was]), verbo([required]), complemento([for, the, in, vitro, generation, of, 'DCs', from, 'Lin(-)Sca-1(+)Kit(+)', 'cells,', common, 'myeloid-restricted', 'progenitors,', and, common, dendritic, cell, 'precursors,', but, not, common, 'lymphoid-restricted', progenitors, or, 'granulocyte-macrophage', 'progenitors,', suggesting, that, 'GATA2', functions, in, the, myeloid, pathway, of, 'DC', differentiation])]). relacion([sujeto(['Moreover,', expression, profiling, demonstrated, reduced, expression, of, 'myeloid-related', 'genes,', including, 'mafb,', and]), verbo([increased]), complemento([expression, of, 'T-lymphocyte-related', 'genes,', including, 'Gata3', and, 'Tcf7,', in, 'Gata2-deficient', 'DC', progenitors])]). relacion([sujeto(['In', 'addition,', 'GATA2', was]), verbo([found]), complemento([to, bind, an, enhancer, element, 190, -, kb, downstream, region, of, 'Gata3,', and, a, reporter, assay, exhibited, significantly, reduced, luciferase, activity, after, adding, this, enhancer, region, to, the, 'Gata3', 'promoter,', which, was, recovered, by, 'GATA', sequence, deletion, within, 'Gata3', +, 190])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, 'GATA2', plays, an, important, role, in, 'cell-fate', specification, toward, the, myeloid, vs, 'T-lymphocyte', lineage, by, regulating, 'lineage-specific', transcription, factors, in, 'DC', 'progenitors,', thereby, contributing, to, 'DC', differentiation])]). relacion([sujeto(['Recent', studies]), verbo([have]), complemento([investigated, the, significance, of, 'GATA3', expression, in, patients, with, various, malignant, tumors])]). relacion([sujeto(['However,', no, previous, studies]), verbo([have]), complemento([evaluated, the, clinicopathological, importance, of, 'GATA3', expression, in, soft, tissue, sarcomas, '(', 'STS)', patients])]). relacion([sujeto(['GATA3-positive', expression, was, significantly]), verbo([associated]), complemento([with, a, higher, mitotic, count, '(', 'P', &, 'lt;', 0.0001, ')'])]). relacion([sujeto(['GATA3-positive', expression, was, significantly]), verbo([associated]), complemento([with, shorter, 'DFS', in, both, univariate, analysis, '(', hazard, ratio, '[', 'HR],', 2.719, ;, 'P', =, 0.012, ')', and, multivariate, analysis, '(', 'HR,', 2.711, ;, 'P', =, 0.014, ')'])]). relacion([sujeto(['GATA3-positive', expression, was, also, significantly]), verbo([associated]), complemento([with, worse, 'OS', in, both, univariate, analysis, '(', 'HR,', 5.73, ;, 'P', =, 0.0007, ')', and, multivariate, analysis, '(', 'HR,', 5.789, ;, 'P', =, 0.0008, ')'])]). relacion([sujeto(['These', results, indicate, that, 'GATA3', is, an, independent, prognostic, factor, and]), verbo([suggest]), complemento([that, evaluation, of, 'GATA3', expression, might, enable, more, effective, clinical, 'follow-up', using, prognostic, stratification, of, 'STS', patients])]). relacion([sujeto(['Aberrant', mucosal, immunity]), verbo([suggests]), complemento([that, 'CD', is, a, 'T', helper, type, 1, cell, '(', 'Th1)-driven', 'disease,', whereas, 'UC', as, 'Th2-driven', response])]). relacion([sujeto(['Patients', with, 'CD', showed]), verbo([increased]), complemento(['IFN-γ', or, 'T-bet', cells, and, decreased, 'IL-13', or, 'Gata3', cells, compared, with, 'UC'])]). relacion([sujeto(['Furthermore,', 'Gata3', cells, were]), verbo([increased]), complemento([in, tumor, necrosis, factor, inhibitor, therapy, nonresponders, compared, with, responders, in, 'CD'])]). relacion([sujeto(['The', 'Th1/Th2', paradigm, can, distinguish, 'CD', from, 'UC', and, may, be, further]), verbo([associated]), complemento([with, response, to, tumor, necrosis, factor, inhibitor, in, 'CD', and, disease, activity, in, patients, with, 'IBD'])]). relacion([sujeto(['GATA']), verbo([binding]), complemento([protein, 3, '(', 'GATA3)', is, a, transcription, 'factor,', which, belongs, to, a, distinct, family, of, tumor, suppressor, genes])]). relacion([sujeto(['It', is]), verbo([involved]), complemento([in, human, cancer, cell, growth, and, 'differentiation,', and, plays, an, important, role, in, cell, proliferation, and, apoptosis])]). relacion([sujeto(['Although,', its, expression]), verbo([has]), complemento([been, reported, in, various, 'cancers,', there, are, limited, data, in, genitourinary, malignancies])]). relacion([sujeto(['Recent', studies]), verbo([found]), complemento(['GATA3', to, be, a, sensitive, marker, for, urothelial, carcinoma, '(', 'UC)', and, associated, with, prognostic, pathologic, features])]). relacion([sujeto(['Its', level, of, expression, was]), verbo([found]), complemento([to, be, an, independent, factor, predicting, cancer, recurrence])]). relacion([sujeto(['The', pattern, of, 'GATA3', 'staining,', when, 'positive,', was, intensely]), verbo([nuclear]), complemento([within, the, clusters, of, malignant, cells])]). relacion([sujeto(['High', 'GATA3', expression, was]), verbo([associated]), complemento([with, larger, tumor, size, in, invasive, 'UC', '(', 3.19, cm, vs])]). relacion([sujeto(['This', data]), verbo([suggest]), complemento([that, 'GATA3', is, a, sensitive, marker, in, confirming, invasive, 'UC,', and, may, be, helpful, in, differentiating, it, from, metastatic, tumors, of, renal, and, prostatic, origin])]). relacion([sujeto(['Furthermore,', strong, 'GATA3', expression, was, noted, to]), verbo([have]), complemento([an, effect, on, tumor, size, in, patients, with, 'UC'])]). relacion([sujeto(['FNA', smears, were, 'cellular,', comprising, predominantly, of, oxyphilic, cells, arranged, in, 'papillary-like', architecture, with, occasional]), verbo([nuclear]), complemento(['grooves,', which, was, mistaken, for, oncocytic, variant, of, papillary, carcinoma, of, the, thyroid])]). relacion([sujeto(['The', 'tumor,', 'unfortunately,', recurred, 7, years, later, with]), verbo([associated]), complemento([multiple, lung, metastases])]). relacion([sujeto(['To']), verbo([report]), complemento([a, clear, cell, renal, cell, carcinoma, recipient, of, a, metastasizing, ductal, carcinoma, of, the, 'breast:', 'A', 'tumor-to-tumor', metastasis])]). relacion([sujeto(['A', 71, 'year-old', woman, with, a, past, history, of, breast, 'carcinoma,', diagnosed, 12, years, 'before,', underwent, a, nephrectomy, for, an, incidental, kidney, mass]), verbo([found]), complemento([in, a, routine, imaging, examination])]). relacion([sujeto(['Awareness', of, this, phenomenon, should, always, be, kept, in, mind, by, urologist, in, patients, with, a, known, history, of, a, previous, malignancy, and, by, pathologists, when]), verbo([finding]), complemento([a, renal, tumor, with, an, unusual, or, dimorphic, morphology])]). relacion([sujeto(['In', contrast, to, other, 'Bet', v, 1, -, related, food, 'allergens,', the, major, carrot, 'allergen,', 'Dau', c, 1, ',']), verbo([has]), complemento([been, suggested, to, induce, food, allergy, independently, from, 'Bet', v, 1])]). relacion([sujeto(['Among', 14, distinct, 'T', 'cell-activating', 'regions,', 'Dau', c, 1139, -, 153, was]), verbo([recognized]), complemento([by, 55, '%', of, the, patients])]). relacion([sujeto(['These', cellular, insights, confirm, that, the, major, carrot, allergen]), verbo([has]), complemento([a, special, status, among, 'Bet', v, 1, -, related, food, allergens])]). relacion([sujeto(['Among', the, genetic, factors, for, isolated, 'AAD', and, autoimmune, polyendocrine, syndrome, type, 2, ',', a, key, role, is, played, by, 'HLA', class, 'II', 'genes:', 'HLA-DRB1*0301-DQA1*0501-DQB1*0201', and, 'DRB1*04-DQA1*0301-DQB1*0302', are, 'positively,', and, 'DRB1*0403', is, 'negatively,']), verbo([associated]), complemento([with, genetic, risk, for, 'AAD'])]). relacion([sujeto(['The', 'MHC', class, 'I', 'chain-related', gene, 'A', '(', 'MICA)', allele, 5.1, is, strongly, and, positively]), verbo([associated]), complemento([with, 'AAD'])]). relacion([sujeto(['We', demonstrate, that, the, transcription, factor, 'MafB', is]), verbo([expressed]), complemento([in, differentiating, keratinocytes, in, mice, and, is, transcriptionally, upregulated, upon, human, keratinocyte, differentiation, 'in vitro'])]). relacion([sujeto(['The', upregulated, genes, in, the, 'MafB(-/-)', epidermis, were, enriched, for, putative]), verbo([target]), complemento([genes, of, the, transcription, factors, 'Gata3,', 'Grhl3,', and, 'Klf4'])]). relacion([sujeto(['Our', results, indicate, that, 'MafB', is, a, component, of, the, gene, expression, program, that]), verbo([regulates]), complemento([epidermal, keratinocyte, differentiation])]). relacion([sujeto(['Following', strict, cytology, smear, screening, 'criteria,']), verbo([targeted]), complemento([next, generation, sequencing, '(', 'NGS)', using, a, 160, cancer, gene, panel, was, performed])]). relacion([sujeto(['The', fidelity, of, cytology, genotyping, to, that, of, paired, surgical, resection, specimens]), verbo([suggests]), complemento([that, 'EUS', 'FNA', represents, a, suitable, surrogate, and, may, complement, the, conventional, stratification, criteria, in, decision, making, for, therapies, and, may, guide, future, biomarker, driven, therapeutic, development])]). relacion([sujeto(['SOCS1', mutations, were, exclusive, to, 'non-relapsing', 'DLBCL,', whereas, primaries, of, relapsing, 'DLBCL', more, commonly, displayed]), verbo([gains]), complemento([of, 10, p15])]). relacion([sujeto(['All', identified, patients, were, invited, to]), verbo([participate]), complemento([in, a, survey])]). relacion([sujeto(['We']), verbo([found]), complemento([higher, prevalence, of, nonsurgical, 'HP', in, 'Norway', than, reported, elsewhere])]). relacion([sujeto(['Genetic', testing, and, autoimmunity, screening, of, idiopathic, 'HP', identified, a, specific]), verbo([cause]), complemento([in, 21, '%'])]). relacion([sujeto(['Further', research, is, necessary, to, unravel, the]), verbo([causes]), complemento([of, idiopathic, 'HP', and, to, improve, the, reduced, 'HRQOL', reported, by, 'HP', patients])]). relacion([sujeto(['Because', of, its, strong, association, with, estrogen, receptor, 'expression,', 'GATA3']), verbo([has]), complemento([markedly, reduced, sensitivity, in, 'triple-negative', breast, cancer, '(', 'TNBC)'])]). relacion([sujeto(['We', also]), verbo([suggest]), complemento([unifying, the, nomenclature, because, vaginal, 'Brenner', tumors, are, most, likely, synonymous, with, tubulosquamous, polyp, '(', 'TSP)', of, the, vagina])]). relacion([sujeto(['While', these, cytokines, are, generally, upregulated, in, inflamed, 'mucosae,', the, key, cytokine, profile, explaining, disease, severity]), verbo([has]), complemento([not, been, determined])]). relacion([sujeto(['Expression', patterns]), verbo([associated]), complemento([with, higher, 'REI', were, determined, by, univariate, and, multivariate, analyses])]). relacion([sujeto(['Multiple', regression, 'analysis,', 'however,']), verbo([found]), complemento([that, joint, expression, of, 'IL-17A,', 'IL-17F,', 'IL-21,', 'RORC,', and, 'TGF-β', was, significantly, predictive, of, 'REI', '(', 'P < 0'])]). relacion([sujeto([1, ')', ',', which, were]), verbo([associated]), complemento([with, increased, and, decreased, 'REI,', respectively])]). relacion([sujeto(['Heat', map, analyses, of, 'RPPA', data, showed, that, 'ER+HER2-', tumors, were, divided, into, 2, groups, by, luminal, 'A/B', signature, '[', protein, expression, of, 'ER,', 'AR,', 'Bcl-2,', 'Bim', '(', 'BCL2L11),', 'GATA3', and, 'INPP4b],', and, this, expression, signature, was, also]), verbo([associated]), complemento([with, the, rate, of, 'PDX', intake])]). relacion([sujeto(['Cell', survival, pathways, such, as, the, 'PI3K/AKT', signaling, and, 'RAS/ERK', pathways, were, more]), verbo([activated]), complemento([in, the, specimens, that, could, be, established, as, 'PDX', in, both, classes])]). relacion([sujeto(['Expression', of, the, 'ER', protein, itself, may]), verbo([have]), complemento([a, bearing, on, the, potential, success, of, an, 'ER+', 'PDX', model])]). relacion([sujeto(['Moreover,', the, comparison, of, 'RPPA', data, between, original, and, 'PDX', tumors]), verbo([suggested]), complemento([that, the, 'selection/adaptation', process, required, to, grow, the, tumors, in, mice, is, unavoidable, for, generation, of, 'ER+', 'PDX', 'models,', and, we, identified, differences, between, patient, tumor, samples, and, paired, 'PDX', tumors])]). relacion([sujeto(['Previous', studies]), verbo([have]), complemento([shown, high, heritability, for, age, of, smoking, initiation, and, 'cessation;', 'however,', 'time-to-event', 'genome-wide', association, studies, aiming, to, identify, underpinning, genes, that, accelerate, or, delay, these, transitions, are, missing, to, date])]). relacion([sujeto([1, ')', ',']), verbo([mediated]), complemento([by, smoking, 'quantity,', and, on, 9, q34])]). relacion([sujeto(['Our', results]), verbo([suggest]), complemento([that, the, functional, effect, of, the, 'TRPM4-SLC6A16', gene, region, deserves, further, 'investigation,', and, that, complex, neurotransmitter, networks, including, dopamine, and, glutamate, may, play, a, critical, role, in, smoking, initiation])]). relacion([sujeto(['There', were, histologic, similarities, between, metastatic, neuroendocrine, neoplasms, and, invasive, mammary, carcinomas, with, neuroendocrine, 'differentiation,', both, of, which, exhibited, neuroendocrine, histologic, features, '(', nested, and, trabecular, 'architecture,', minimal, tubular, 'differentiation,', and, characteristic]), verbo([nuclear]), complemento(['features)'])]). relacion([sujeto(['Only', one, case, of, the, invasive, mammary, carcinomas, with, neuroendocrine, differentiation, was, modified, 'Bloom-Richardson', grade, 1, '(', largely, due, to, minimal, tubular, differentiation, on, most, such, 'tumors),', and, the, invasive, mammary, carcinomas, with, neuroendocrine, differentiation, were, often]), verbo([associated]), complemento([with, in, situ, carcinoma])]). relacion([sujeto(['The', intimate, link, between, location, of, fat, accumulation, and, metabolic, disease, risk, and, 'depot-specific', differences, is, well, 'established,', but, how, these, differences, between, depots, are]), verbo([regulated]), complemento([at, the, molecular, level, remains, largely, unclear])]). relacion([sujeto(['Here', we, show, that, 'TRIP-Br2']), verbo([mediates]), complemento([endoplasmic, reticulum, '(', 'ER)', 'stress-induced', inflammatory, responses, in, visceral, fat])]). relacion([sujeto(['We']), verbo([find]), complemento([that, ablation, of, 'TRIP-Br2', ameliorates, both, chemical, and, physiological, 'ER', 'stress-induced', inflammatory, and, acute, phase, response, in, 'adipocytes,', leading, to, lower, circulating, levels, of, inflammatory, cytokines])]). relacion([sujeto(['Taken', 'together,', our, study, identifies, molecular, regulators, of, inflammatory, response, in, visceral, fat, 'that-given', that, these, pathways, are]), verbo([conserved]), complemento([in, 'humans-might', serve, as, potential, therapeutic, targets, in, obesity])]). relacion([sujeto(['Over', thepast, 'decade,there']), verbo([has]), complemento([been, an, exponential, increase, in, interest, and, progress, in, understanding, of, the, development, of, the, inner, ear, and, of, hair, 'cells,', aiming, to, gain, insights, into, hair, cell, repair, or, even, regeneration])]). relacion([sujeto(['In', hair, cell, 'development,', various, transcription, factors]), verbo([have]), complemento([been, found, to, be, involved, in, the, processes, of, hair, cell, 'proliferation,', differentiation, and, survival])]). relacion([sujeto(['Among', these, transcription, 'factors,', 'Math1,', 'Gata3,', 'Sox2', and, 'Atoh1']), verbo([have]), complemento([been, highlighted, for, their, crucial, role, in, the, fate, of, hair, cells])]). relacion([sujeto(['The', uniqueness, of, this, pseudoendometrioid, carcinoma, lies, in, the, fact, that, its, mesonephric, nature, is, revealed, by, the, origin, from, a, papillary, cystadenoma, of, the, broad, 'ligament,', where, remnants, of, the, mesonephric, duct, are, 'seated,', and, the, immunohistochemical, 'profile,', particularly, a, uniform, negativity, for, estrogen, and, progesterone, 'receptors,', 'apical-luminal', positivity, for, 'CD10,', and, strong]), verbo([nuclear]), complemento([positivity, for, 'GATA3'])]). relacion([sujeto(['KLK6', is]), verbo([expressed]), complemento([in, normal, mammary, tissues, and, is, aberrantly, regulated, in, breast, cancer])]). relacion([sujeto([those]), verbo([found]), complemento([in, normal, mammary, 'tissues,', 'KLK6', acts, as, a, tumor, suppressor, in, human, breast, cancer])]). relacion([sujeto([50, -, 100, -, fold, higher, than, 'normal),', a, characteristic, of, a, subset, of, human, breast, cancers, is]), verbo([associated]), complemento([with, increased, tumorigenicity, '(', 'Pampalakis', 'et al'])]). relacion([sujeto(['Here,', we, stably, transfected, 'KLK6-non-expressing', 'MDA-MB-231', breast, cancer, cells, with, the, 'full-length', 'KLK6', cDNA, to, overexpress, 'KLK6', at, levels, comparable, to, those, observed, in, 'patients,', and, investigated, potential, oncogenic, miRNA, networks]), verbo([regulated]), complemento([by, these, abnormally, high, 'KLK6', expression, levels, and, increased, activity, of, this, serine, protease])]). relacion([sujeto(['Integrated', experimental, and, bioinformatics, analyses, identified, convergent, miRNA, networks]), verbo([targeting]), complemento([the, cell, 'cycle,', 'MYC,', 'MAPK,', and, other, signaling, pathways])]). relacion([sujeto(['In', large, clinical, 'datasets,', significant, correlations, between, 'KLK6', and, downstream, 'MAPK', and, 'MYC']), verbo([targets]), complemento([at, both, the, 'RNA', and, protein, levels, was, 'confirmed,', as, well, as, negative, correlation, with, 'GATA3'])]). relacion([sujeto(['It', was, also, demonstrated, that, 'KLK6', overexpression, and, likely, its, proteolytic, activity, is]), verbo([associated]), complemento([with, alterations, in, downstream, miRNAs, and, their, 'targets,', and, these, differ, with, the, molecular, subtypes, of, breast, cancer])]). relacion([sujeto(['Thymocyte', 'CD4+', cells]), verbo([have]), complemento([been, reported, to, play, an, important, role, in, the, pathogenesis, of, both, 'AAU', and, 'AS'])]). relacion([sujeto(['To', test, whether, the, copy, number, variations, '(', 'CNVs)', of, 'CD4+', 'T', cell, transcription, factor, genes, including, 'T-bet,', 'GATA']), verbo([binding]), complemento([protein, 3, '(', 'GATA)-3,', related, orphan, receptor, 'C', '(', 'RORC)', and, forkhead, box, protein, 3, '(', 'FOXP3)', are, associated, with, acute, anterior, uveitis, either, in, the, presence, or, absence, of, ankylosing, spondylitis, '(', 'AAU+AS+;', 'AAU+AS-)'])]). relacion([sujeto(['The', frequency, of, a, high, copy, number, '(', 'CN)', of, 'T-bet', was]), verbo([increased]), complemento([in, 'AAU+AS+', as, well, as, 'AAU+AS-', patients, when, compared, with, controls, '(', 'P', value, after, 'Bonferroni', correction, '[', 'P(corr)]', =, 4.3, ×, 10, '(', -, 5, ')', ;, odds, ratio, '[', 'OR]', =, 2.0, and, 'P(corr)', =, 1.2, ×, 10, '(', -, 8, ')', ;, 'OR', =, 2.3, ',', 'respectively)'])]). relacion([sujeto(['A', higher, frequency, of, 'CN', of, 'FOXP3', was]), verbo([found]), complemento([in, female, 'AAU+AS+', patients, and, female, 'AAU+AS-', patients, '(', 'P(corr)', =, 0.005, ',', 'OR', =, 5.9, and, 'P(corr)', =, 0.004, ',', 'OR', =, 4.9, ',', respectively, ')'])]). relacion([sujeto(['No', association, was]), verbo([found]), complemento([between, 'CNVs', of, 'RORC', and, 'AAU+AS-', or, 'AAU+AS+', patients])]). relacion([sujeto(['A', high, copy, number, of, 'T-bet', and, 'GATA-3']), verbo([confers]), complemento([susceptibility, to, 'AAU', and, 'AS,', and, a, high, copy, number, of, 'FOXP3', confers, susceptibility, to, female, patients, with, 'AAU', either, with, or, without, 'AS'])]). relacion([sujeto(['Although', the, chlorinated, flame, retardant, 'Dechlorane', '(', 'Dec)', 602]), verbo([has]), complemento([been, detected, in, 'food,', human, 'blood,', and, breast, 'milk,', there, is, limited, information, on, potential, health, 'effects,', including, possible, immunotoxicity])]). relacion([sujeto(['Splenic', 'CD4+', and, 'CD8+', 'T', cell, subsets, were]), verbo([decreased]), complemento([compared, with, vehicle, 'controls,', and, apoptosis, was, significantly, increased, in, splenic, 'CD4+', 'T', cells])]). relacion([sujeto(['To', our, 'knowledge,', we, are, the, first, to]), verbo([report]), complemento([evidence, of, the, effects, of, 'Dec', 602, on, immune, function, in, 'mice,', with, findings, indicating, that, 'Dec', 602, exposure, favored, 'Th2', responses, and, reduced, 'Th1', function])]). relacion([sujeto(['Chemoattractant', 'receptor-homologous', molecule]), verbo([expressed]), complemento([on, 'Th2', cells, '(', 'CRTh2)', is, a, receptor, for, 'PGD2', and, expressed, by, 'T', 'cells,', 'eosinophils,', 'basophils,', and, 'ILC2', cells])]). relacion([sujeto(['CRTh2', expression, by, 'CD4(+)', 'T', cells, identifies, the, 'Th2', 'subset,', and, these, cells]), verbo([have]), complemento([been, characterized, as, 'allergen-specific', central, memory, 'Th2', cells])]). relacion([sujeto(['Recently,', activation, of, the, 'PGD2', -, 'CRTh2', pathway, in, the, lungs, was]), verbo([associated]), complemento([with, severe, asthma])]). relacion([sujeto(['Peripheral', blood, cells]), verbo([expressing]), complemento(['CRTh2', were, characterized, by, flow, cytometry, and, 'qRT-PCR'])]). relacion([sujeto(['The', proportion, of, 'CD4(+)', 'CRTh2(+)', 'T', cells, was]), verbo([associated]), complemento([with, lower, lung, function, and, was, highest, in, severe, asthmatics, that, exacerbated, in, the, last, year])]). relacion([sujeto(['We', present, the, second]), verbo([reported]), complemento([mammary, analog, secretory, carcinoma, '(', 'MASC)', apparently, arising, in, the, thyroid, and, propose, a, potential, close, relationship, to, 'ETV6-NTRK3', fusion, papillary, thyroid, carcinoma])]). relacion([sujeto(['Imaging', studies, showed, a, tumor]), verbo([involving]), complemento([most, of, the, thyroid, with, enlarged, regional, lymph, nodes])]). relacion([sujeto(['Histologic', features, included, mixed, 'microcystic,', 'solid,', follicular, and, papillary, 'architecture,', prominent, 'nucleoli,', abundant]), verbo([nuclear]), complemento([grooves, and, rare, nuclear, 'pseudo-inclusions'])]). relacion([sujeto(['At', the, molecular, 'level,', the, 'ETV6-NTRK3', fusion, in, this, patient]), verbo([involved]), complemento([exons, reported, in, the, rare, &, 'quot;papillary', thyroid, 'carcinoma"', with, this, translocation])]). relacion([sujeto(['F4/80(-)CD11b(+)Gr(+)', 'cells,', presumed, to, be, 'neutrophils,', were]), verbo([reported]), complemento([to, accumulate, around, encysting, larvae, in, intestinal, tissue, during, primary, 'infection,', but, their, exact, identity, and, role, remain, unclear])]). relacion([sujeto(['We', observed, significant]), verbo([increases]), complemento([in, 'F4/80(-)CD11b(hi)Gr1(hi)', cells, in, mesenteric, lymph, nodes, '(', 'MLNs)', and, spleen, after, primary, but, not, challenge, 'infection;', a, high, proportion, of, these, cells, expressed, 'Ly6G', and, 'Ly6C'])]). relacion([sujeto(['These', 'cells,', which, phenotypically, resemble, 'myeloid-derived', suppressor, cells, '(', 'MDSC),']), verbo([increased]), complemento([in, lamina, propria, '(', 'LP)', early, during, primary, infection])]). relacion([sujeto(['Increased', 'MDSC', were]), verbo([associated]), complemento([with, low, numbers, of, alternatively, activated, macrophages, '(', 'AAMØ)', in, 'LP', and, 'CD4(+)GATA3(+)', 'T', cells, and, 'AAMØ', in, 'MLN', and, spleen])]). relacion([sujeto([polygyrus, 'bakeri-infected', mice]), verbo([suppressed]), complemento(['OVA-specific', 'CD4(+)', 'T-cell', proliferation, via, a, nitric, 'oxide-dependent', mechanism, and, 'parasite-specific', 'IL-4', secretion, in, vitro])]). relacion([sujeto(['Adoptive', transfer, of, 'CD11c(-)CD11b(+)Gr1(+)', cells, from, mice, with, primary, infection, resulted, in, significantly, higher, adult, worm, burdens, and]), verbo([increased]), complemento([egg, production, in, naïve, 'B6', recipients, infected, with, 'H'])]). relacion([sujeto([polygyrus, bakeri, infection]), verbo([induces]), complemento([a, novel, subset, of, 'MDSC', that, suppress, 'CD4(+)', 'Th2', responses, and, promote, chronic, infection])]). relacion([sujeto(['Infections', with, helminth, parasites, are, endemic, in, the, developing, world, and, are, a]), verbo([target]), complemento([for, intervention, with, new, therapies])]). relacion([sujeto(['At', day, 7, 'postinfection,', 'MIF-deficient', '(', 'MIF(-/-))', mice, had, reduced, parasite, burden, and, mounted, an]), verbo([enhanced]), complemento([type, 2, immune, response, '(', 'Th2),', including, increased, 'Gata3', expression, and, 'interleukin-13', '(', 'IL-13)', production, in, the, mesenteric, lymph, nodes, '(', 'MLNs)'])]). relacion([sujeto(['Bone', marrow, reconstitution, demonstrated, that, 'MIF', produced, from, hematopoietic, cells, was, crucial, and, 'Rag1(-/-)', reconstitution]), verbo([provided]), complemento([direct, evidence, that, 'MIF(-/-)', 'CD4(+)', 'T', cells, were, responsible, for, the, augmented, parasite, clearance])]). relacion([sujeto(['MIF(-/-)', 'CD4(+)', 'T', cells, produced, less, 'IL-6', 'postinfection,', which, correlated, with]), verbo([enhanced]), complemento(['Th2', responses])]). relacion([sujeto(['MIF(-/-)', 'CD4(+)', 'T', cells, exhibited, lower]), verbo([nuclear]), complemento(['factor-κB', 'activation,', potentially, explaining, the, reduction, in, 'IL-6'])]). relacion([sujeto(['Finally,', we, demonstrated]), verbo([enhanced]), complemento([clearance, of, the, parasite, and, 'Th2', response, in, 'wild-type', mice, treated, with, the, 'MIF', tautomerase, 'inhibitor,', 'sulforaphane,', a, compound, found, naturally, found, in, cruciferous, vegetables])]). relacion([sujeto(['Following', 'Notch1-dependent', 'T-cell', lineage, specification, during, which, the, first, 'T-cell', lineage, genes, are]), verbo([expressed]), complemento([and, myeloid, and, dendritic, cell, potential, is, 'lost,', 'T-cell', specific, transcription, factors, subsequently, induce, 'T-cell', commitment, by, repressing, residual, natural, killer, '(', 'NK)-cell', potential])]). relacion([sujeto(['How', these, processes, are]), verbo([regulated]), complemento([in, human, is, poorly, 'understood,', especially, since, efficient, 'T-cell', lineage, commitment, requires, a, reduction, in, 'Notch', signalling, activity, following, 'T-cell', specification])]). relacion([sujeto(['Here,', we, show, that, 'GATA3,', in, contrast, to, 'TCF1,', controls, human, 'T-cell', lineage, commitment, through, direct, regulation, of, three, distinct, 'processes:', repression, of, 'NK-cell', 'fate,', upregulation, of, 'T-cell', lineage, genes, to]), verbo([promote]), complemento([further, differentiation, and, restraint, of, 'Notch', activity])]). relacion([sujeto(['Repression', of, the, 'Notch1']), verbo([target]), complemento([gene, 'DTX1', hereby, is, essential, to, prevent, 'NK-cell', differentiation])]). relacion([sujeto(['Estrogen', 'receptor-α', '(', 'ERα)']), verbo([mediates]), complemento([the, essential, biological, function, of, estrogen, in, breast, development, and, tumorigenesis])]). relacion([sujeto(['Multiple', 'mechanisms,', including, pioneer, 'factors,', coregulators, and, epigenetic, modifications]), verbo([have]), complemento([been, identified, as, regulators, of, 'ERα', signaling, in, breast, cancer])]). relacion([sujeto(['However,', previous, studies, of, 'ERα', regulation]), verbo([have]), complemento([focused, on, luminal, and, 'HER2-positive', subtypes, rather, than, 'basal-like', breast, cancer, '(', 'BLBC),', in, which, 'ERα', is, underexpressed])]). relacion([sujeto(['In', 'addition,', mechanisms, that, account, for, the]), verbo([decrease]), complemento([or, loss, of, 'ER', expression, in, recurrent, tumors, after, endocrine, therapy, remain, elusive])]). relacion([sujeto(['Here,', we, demonstrate, a, novel, 'FOXC1-driven', mechanism, that]), verbo([suppresses]), complemento(['ERα', expression, in, breast, cancer])]). relacion([sujeto(['We']), verbo([find]), complemento([that, 'FOXC1', competes, with, 'GATA-binding', protein, 3, '(', 'GATA3)', for, the, same, binding, regions, in, the, 'cis-regulatory', elements, upstream, of, the, 'ERα', gene, and, thereby, downregulates, 'ERα', expression, and, consequently, its, transcriptional, activity])]). relacion([sujeto(['Counteracting', the, action, of, 'GATA3', at, the, 'ERα', promoter, 'region,', overexpression, of, 'FOXC1', hinders, recruitment, of, 'RNA', polymerase, 'II', and]), verbo([increases]), complemento([histone, 'H3K9', trimethylation, at, 'ERα', promoters])]). relacion([sujeto(['Furthermore,', in, breast, cancer, patients, with, 'ER-positive', primary, tumors, who, received, adjuvant, tamoxifen, 'treatment,', 'FOXC1', expression, is]), verbo([associated]), complemento([with, decreased, or, undetectable, 'ER', expression, in, recurrent, tumors])]). relacion([sujeto(['This', study]), verbo([suggests]), complemento([a, new, paradigm, to, study, 'ERα', regulation, during, breast, cancer, progression, and, indicates, a, role, of, 'FOXC1', in, the, modulation, of, cellular, response, to, endocrine, treatment])]). relacion([sujeto(['During', mouse, early, 'embryogenesis,', blastomeres]), verbo([increase]), complemento([in, number, by, the, morula, stage])]). relacion([sujeto(['TE']), verbo([provides]), complemento([an, important, liquid, environment, for, 'ICM', development])]). relacion([sujeto(['The', results, indicated, that, 'MPP', treatment]), verbo([inhibits]), complemento([blastocyst, formation, in, a, 'dose-dependent', 'manner,', while, 'PPT,', at, proper, 'concentration,', promotes, the, cavitation, ratio, of, mouse, embryos])]). relacion([sujeto(['Immunofluorescence', staining, results, showed, that, 'MPP', significantly]), verbo([decreased]), complemento([the, nuclear, expression, of, 'CDX2', in, 'morula,', but, no, significant, changes, of, 'OCT4', were, observed])]). relacion([sujeto(['Overall,', these, results, indicated, that, 'ERα', might, affect, mouse, embryo, cavitation, by]), verbo([regulating]), complemento(['TE', lineage, differentiation])]). relacion([sujeto([-, 'To', examine, immunohistochemical, markers, in, the, context, of, sarcomatoid, 'UCa,', including, those]), verbo([associated]), complemento([with, 'epithelial-to-mesenchymal', transition])]). relacion([sujeto(['The', presence, of, myxoid, or, chordoid, features, was]), verbo([associated]), complemento([with, reduced, survival, '(', 'P', &, 'lt;'])]). relacion([sujeto([-, 'Sarcomatoid', 'UCa', is, an, aggressive, form, of, 'UCa', that, frequently]), verbo([expresses]), complemento(['epithelial-to-mesenchymal', transition, 'markers,', suggesting, a, possible, mechanism, associated, with, aggressive, tumor, behavior])]). relacion([sujeto(['In', breast, 'cancer,', 'GATA3', mutations]), verbo([have]), complemento([been, associated, with, a, favorable, prognosis, and, the, response, to, neoadjuvant, aromatase, inhibitor, treatment])]). relacion([sujeto(['In', a, retrospective, study, consisting, of, 235, 'hormone-naive', patients, with, 'ER-positive', breast, cancer, who, received, tamoxifen, as, 'first-line', treatment, for, recurrent, 'disease,', 'GATA3', mutations, '(', in, 14.0, '%', of, 'patients)', did, not, significantly]), verbo([associate]), complemento([with, either, the, overall, response, rate, '(', 'ORR)', or, with, the, length, of, 'progression-free', survival, '(', 'PFS)', after, the, start, of, tamoxifen, therapy])]). relacion([sujeto(['Interestingly,', among, 148, patients, for, whom, both, mutation, and, mRNA, expression, data, were, 'available,', 'GATA3', mutations]), verbo([associated]), complemento([with, an, increased, expression, of, 'GATA3'])]). relacion([sujeto(['Evaluation', of, the, clinical, significance, of, 'GATA3', mRNA, revealed, that, it, was]), verbo([associated]), complemento([with, prolonged, 'PFS,', but, not, with, the, 'ORR,', also, in, multivariate, analysis])]). relacion([sujeto(['Besides', 'GATA3', 'mutation,', other, mechanisms, must, exist, that, underlie]), verbo([increased]), complemento(['GATA3', levels])]). relacion([sujeto(['We', also, examined, potential, mechanisms, by, which, dual, 'Dll4', and, 'VEGF']), verbo([targeting]), complemento([inhibit, tumor, growth, using, immunohistochemical, staining, for, apoptosis, and, proliferation, markers])]). relacion([sujeto(['Reverse-phase', protein, arrays, were, used, to, identify, potential, downstream]), verbo([targets]), complemento([of, 'Dll4', blockade])]). relacion([sujeto(['Dual']), verbo([targeting]), complemento([of, 'VEGF', and, 'Dll4', with, murine, 'REGN1035', showed, superior, antitumor, effects, in, ovarian, cancer, models, compared, with, either, monotherapy])]). relacion([sujeto(['In', the, 'A2780', 'model,', 'REGN1035', '(']), verbo([targets]), complemento([murine, 'Dll4)', or, 'REGN421', '(', targets, human, 'Dll4)', reduced, tumor, weights, by, 62, '%', and, 82, '%', ',', 'respectively;', aflibercept, alone, reduced, tumor, weights, by, 90, '%'])]). relacion([sujeto(['The', superior, antitumor, effects, of, 'REGN1035', and, aflibercept, were, related, to]), verbo([increased]), complemento([apoptosis, in, tumor, cells, compared, with, the, monotherapy])]). relacion([sujeto(['We', also]), verbo([found]), complemento([that, 'GATA3', expression, was, significantly, increased, in, tumor, stroma, from, the, mice, treated, with, 'REGN1035', combined, with, docetaxel, or, 'aflibercept,', suggesting, an, indirect, effect, of, these, combination, treatments, on, the, tumor, stroma])]). relacion([sujeto(['These', findings, identify, that, dual]), verbo([targeting]), complemento([of, 'Dll4', and, 'VEGF', is, an, attractive, therapeutic, approach])]). relacion([sujeto(['S100A8', and, 'S100A9']), verbo([have]), complemento([been, identified, to, be, expressed, by, epithelial, cells, involved, in, malignancy])]). relacion([sujeto(['In', the, present, 'study,', the, transcriptional, levels, of, 'S100A8', and, 'S100A9', were, investigated, in, various, subtypes, of, breast, cancer, '(', 'BC),', and, the, correlation, with, estrogen, receptor, 1, '(', 'ESR1)', and, 'GATA']), verbo([binding]), complemento([protein, 3, '(', 'GATA3)', gene, expression, was, evaluated, using, microarray, datasets])]). relacion([sujeto(['S100A8/A9']), verbo([induced]), complemento([a, 10, -, fold, decrease, in, the, mRNA, levels, of, 'ESR1', in, 'MCF-7', cells])]). relacion([sujeto(['Poor', 'OS', was]), verbo([associated]), complemento([with, high, expression, levels, of, 'S100A9,', but, not, with, high, expression, levels, of, 'S100A8', in, 'BC'])]). relacion([sujeto(['In', 'conclusion,', strong, expression, and, secretion, of, 'S100A8/A9', may, be]), verbo([associated]), complemento([with, the, loss, of, estrogen, receptor, in, 'BC,', and, may, be, involved, in, the, poor, prognosis, of, 'Her2+/basal-like', subtypes, of, 'BC'])]). relacion([sujeto(['Different', genes, are]), verbo([associated]), complemento([with, categorical, classifications, of, asthma, severity])]). relacion([sujeto(['However,', continuous, outcomes, should, be, used, to, catch, the, heterogeneity, of, asthma, phenotypes, and, to]), verbo([increase]), complemento([the, power, in, association, studies])]). relacion([sujeto(['SNP', rs848, in, the, 'IL13', gene, region, '(', 'IL5/RAD50/IL13/IL4)', was]), verbo([associated]), complemento([with, 'STS', '(', 'TG/GG', vs, 'TT', 'genotype:', uncorrected, 'p-value', =, 6.0e-5, ',', 'FDR-corrected', 'p-value', =, 0.04, ')', ',', whereas, rs20541, in, the, same, gene, 'region,', in, linkage, disequilibrium, with, rs848, '(', 'r(2)', =, 0.94, ')', in, our, 'sample,', did, not, reach, the, statistical, significance, after, adjusting, for, multiple, testing, '(', 'TC/CC', vs, 'TT:', uncorrected, 'p-value', =, 0.0003, ',', 'FDR-corrected', 'p-value', =, 0.09, ')'])]). relacion([sujeto(['After', adjusting, for, multiple, testing, and, potential, 'confounders,', 'SNP', rs848, in, the, 'IL13', gene, region, is, significantly]), verbo([associated]), complemento([with, a, continuous, measure, of, symptom, severity, in, adult, subjects, with, ever, asthma])]). relacion([sujeto(['IgG4-related', disease, '(', 'IgG4-RD)', is, a, systemic, condition, of, unknown]), verbo([cause]), complemento([characterized, by, highly, fibrotic, lesions, with, dense, lymphoplasmacytic, infiltrates])]). relacion([sujeto(['The', dominant, 'T cells', infiltrating, a, range, of, inflamed, 'IgG4-RD', tissue, sites, were, clonally, expanded, 'CD4(+)', 'CTLs', that]), verbo([expressed]), complemento(['SLAMF7,', granzyme, 'A,', 'IL-1β,', and, 'TGF-β1'])]). relacion([sujeto(['Clinical', remission]), verbo([induced]), complemento([by, 'rituximab-mediated', 'B-cell', depletion, was, associated, with, a, reduction, in, numbers, of, 'disease-associated', 'CD4(+)', 'CTLs'])]). relacion([sujeto(['High', serum, sCD30, levels, are]), verbo([associated]), complemento([with, inflammatory, disorders, and, poor, outcome, in, renal, transplantation])]). relacion([sujeto(['Additionally,', we, evaluated, the, same, transcripts, and]), verbo([release]), complemento([of, sCD30, and, 32, cytokines, after, allogeneic, and, polyclonal, 'T-cell', activation])]). relacion([sujeto(['In', peripheral, 'blood,', 'ESRDP', showed]), verbo([increased]), complemento([levels, of, 't-bet', and, 'GATA3', transcripts, compared, to, healthy, controls, '(', 'HC)', '(', both, 'P<0'])]). relacion([sujeto(['Polyclonal', and, allogeneic, stimulation]), verbo([induced]), complemento([higher, levels, of, 'CD30', transcripts, in, 'ESRDP', than, in, 'HC', '(', both, 'P<0'])]). relacion([sujeto(['Reflecting', an]), verbo([activated]), complemento([immune, 'state,', 'ESRDP', exhibited, after, allostimulation, upregulation, of, 'CD30', transcripts, in, 'T', 'cells,', which, was, associated, with, 'Th1', and, proinflammatory, responses])]). relacion([sujeto(['Male', breast, cancer, is, 'rare,', and, its, genomic, landscape]), verbo([has]), complemento([yet, to, be, fully, characterized])]). relacion([sujeto(['Fifty-nine', male, breast, cancers, were, subtyped, by, 'immunohistochemistry,', and, 'tumor-normal', pairs, were, microdissected, and, subjected, to, massively, parallel, sequencing]), verbo([targeting]), complemento([all, exons, of, 241, genes, frequently, mutated, in, female, breast, cancers, or, 'DNA-repair', related])]). relacion([sujeto(['In', 'addition,', male, breast, cancers, were]), verbo([found]), complemento([to, be, significantly, enriched, for, mutations, affecting, 'DNA', 'repair-related', genes])]). relacion([sujeto(['Male', breast, cancers, less, frequently, harbor, somatic, genetic, alterations, typical, of, 'ER-positive/HER2-negative', female, breast, 'cancers,', such, as, 'PIK3CA', and, 'TP53', mutations, and]), verbo([losses]), complemento([of, 16, 'q,', suggesting, that, at, least, a, subset, of, male, breast, cancers, are, driven, by, a, distinct, repertoire, of, somatic, changes])]). relacion([sujeto(['Previous', studies]), verbo([have]), complemento([shown, evidence, for, association, between, risk, of, 'ALL', and, variation, within, 'IKZF1,', 'ARID5B,', 'CEBPE,', 'CDKN2A,', 'GATA3,', and, 'BM1-PIP4K2A', genes])]). relacion([sujeto(['Pathway', analysis, results, indicate, that, different, 'ALL', subtypes, may]), verbo([involve]), complemento([distinct, biologic, mechanisms])]). relacion([sujeto(['Notably,', these, pathways, are, connected, to, downstream, 'MAPK', or, 'Wnt', signaling, pathways, which]), verbo([have]), complemento([been, linked, to, 'B-cell', malignancies])]). relacion([sujeto(['Several', candidate, genes, for, 'ALL,', such, as, 'COL6A6', and, 'COL5A1,', were, identified, through]), verbo([targeted]), complemento([maximum, likelihood, estimation])]). relacion([sujeto(['The', findings, demonstrate, that, newly, developed, bioinformatics, tools, and, causal, inference, methods, can]), verbo([provide]), complemento([insights, to, furthering, our, understanding, of, the, pathogenesis, of, leukemia])]). relacion([sujeto(['As', 'DCA']), verbo([inhibits]), complemento([aerobic, 'glycolysis,', which, is, a, prerequisite, for, 'CD4+', 'T-cell', proliferation, and, differentiation, into, effector, 'T-cells,', its, possible, immunosuppressive, role, in, mixed, lymphocyte, reaction, '(', 'MLR),', a, model, of, 'alloreactivity,', was, investigated])]). relacion([sujeto(['CD4+', 'T‑cells', were, then, isolated, from, the, 'MLRs', and, the, expression, of, cleaved, 'caspase‑3,', various, enzymes]), verbo([involved]), complemento([in, 'glycolysis,', and, the, signature, transcription, factors, of, 'CD4+', 'T‑cell', subsets, were, evaluated, by, western, blotting])]). relacion([sujeto(['In', 'MLRs,', 'DCA']), verbo([decreased]), complemento([glucose, consumption, and, aerobic, 'glycolysis,', while, it, exerted, a, negligible, effect, on, cell, proliferation])]). relacion([sujeto(['In', 'CD4+', 'T‑cells,', 'DCA']), verbo([induced]), complemento(['apoptosis,', and, decreased, the, expression, of, glucose, 'trasporter‑1,', hexokinase, 'II,', lactate, 'dehydrogenase‑A', and, phosphorylated, pyruvate, 'dehydrogenase,', while, it, increased, total, pyruvate, dehydrogenase])]). relacion([sujeto(['In', 'addition,', 'DCA']), verbo([increased]), complemento([the, expression, of, transcription, factor, forkhead, box, 'P3,', whereas, it, decreased, the, expression, of, 'T‑box', transcription, factor, 'TBX21,', 'trans‑acting', 'T-cell-specific', transcription, factor, 'GATA‑3', and, retinoic, acid, receptor, related, orphan, 'receptor‑γt'])]). relacion([sujeto(['In', 'conclusion,', in, alloreactive, 'CD4+', 'T‑cells,', 'DCA']), verbo([inhibits]), complemento([aerobic, 'glycolysis,', induces, apoptosis, and, favors, differentiation, towards, the, regulatory, 'T‑cell', subset])]). relacion([sujeto(['HIV-infected', persons, are, at, greater, risk, of, developing, tuberculosis, '(', 'TB)', even, before, profound, 'CD4']), verbo([loss]), complemento(['occurs,', suggesting, that, 'HIV', alters, 'CD4(+)', 'T', cell, functions, capable, of, containing, bacterial, replication])]). relacion([sujeto(['An', effective, immune, response, to, 'Mycobacterium', tuberculosis, most, likely, relies, on, the, development, of, a, balanced, 'CD4', 'response,', in, which, distinct, 'CD4(+)', 'Th', subsets]), verbo([act]), complemento([in, synergy, to, control, the, infection])]). relacion([sujeto(['tuberculosis-specific', 'CD4(+)', 'T', cells, from, healthy, individuals]), verbo([have]), complemento([the, ability, to, exhibit, a, broad, spectrum, of, 'Th', 'subsets,', defined, by, specific, patterns, of, transcription, factor, coexpression])]). relacion([sujeto(['tuberculosis-specific', 'CD4(+)', 'T', cells, was, significantly]), verbo([decreased]), complemento(['(', p, =, 0.002, ')', compared, with, 'HIV-uninfected', 'individuals,', a, change, that, correlated, inversely, with, 'HIV', viral, load, '(', p, =, 0.0007, ')', and, plasma, 'TNF-α', '(', p, =, 0.027, ')'])]). relacion([sujeto(['Our', data, demonstrate, an, important, balance, in, 'Th', subset, diversity, defined, by, 'lineage-defining', transcription, factor, coexpression, profiles, that, is, disrupted, by, 'HIV', infection, and]), verbo([suggest]), complemento([a, role, for, 'HIV', in, impairing, 'TB', immunity, by, altering, the, equilibrium, of, 'M'])]). relacion([sujeto(['Transcription', 'factor-dependent', cellular, reprogramming, is, integral, to, normal, development, and, is, central, to, production, of]), verbo([induced]), complemento([pluripotent, stem, cells])]). relacion([sujeto(['This', process, typically]), verbo([requires]), complemento([pioneer, transcription, factors, '(', 'TFs)', to, induce, de, novo, formation, of, enhancers, at, previously, closed, chromatin])]). relacion([sujeto(['In', some, 'instances,', 'GATA3']), verbo([binds]), complemento([previously, inaccessible, 'chromatin,', characterized, by, 'stable,', positioned, nucleosomes, where, it, induces, nucleosome, 'eviction,', alters, local, histone, 'modifications,', and, remodels, local, chromatin, architecture])]). relacion([sujeto(['At', other, 'loci,', 'GATA3']), verbo([binding]), complemento([induces, nucleosome, sliding, without, concomitant, generation, of, accessible, chromatin])]). relacion([sujeto(['Deletion', of, the, transactivation, domain]), verbo([retains]), complemento([the, chromatin, binding, ability, of, 'GATA3', but, cripples, chromatin, reprogramming, 'ability,', resulting, in, failure, to, induce, 'MET'])]). relacion([sujeto(['These', data]), verbo([provide]), complemento([mechanistic, insights, into, 'GATA3-mediated', chromatin, reprogramming, during, 'MET,', and, suggest, unexpected, complexity, to, 'TF', pioneering])]). relacion([sujeto(['Successful', reprogramming]), verbo([requires]), complemento([stable, binding, to, a, nucleosomal, 'site;', activation, 'domain-dependent', recruitment, of, 'co-factors', including, 'BRG1,', the, 'ATPase', subunit, of, the, 'SWI/SNF', chromatin, remodeling, 'complex;', and, appropriate, genomic, context])]). relacion([sujeto(['The', resulting, model]), verbo([provides]), complemento([a, new, conceptual, framework, for, de, novo, enhancer, establishment, by, a, pioneer, 'TF'])]). relacion([sujeto(['The', mRNA, levels, of, 'ROG,', 'GATA3', and, 'T-bet', in, the, 'PBMCs', are, obviously, 'up-regulated', in, 'CHB', patients, and, these, 3, genes, may]), verbo([participate]), complemento([in, the, progression, of, 'CHB'])]). relacion([sujeto(['ROG', plays, an, important, role, in, correcting, and]), verbo([maintaining]), complemento([the, new, balance, of, 'Th1/Th2'])]). relacion([sujeto(['Hemocytes', are, the, effective, immunocytes, in, 'bivalves,', which]), verbo([have]), complemento([been, reported, to, be, derived, from, 'stem-like', cells, in, gill, epithelium, of, oyster])]). relacion([sujeto(['In', the, present, 'work,', a]), verbo([conserved]), complemento([haematopoietic, transcription, factor, 'Tal-1/Scl', '(', 'Stem', 'Cell', 'Leukemia)', was, identified, in, 'Pacific', oyster, '(', 'Cg-SCL),', and, it, was, evolutionarily, close, to, the, orthologs, in, deuterostomes])]). relacion([sujeto(['During', the, larval, developmental, 'stages,', the, mRNA, transcripts, of, 'Cg-SCL', gradually]), verbo([increased]), complemento([after, fertilization, and, peaked, at, early, trochophore, larvae, stage, '(', 10, &, 'nbsp;hpf,', hours, post, 'fertilization),', then, sharply, decreased, in, late, trochophore, larvae, stage, '(', 15, &, 'nbsp;hpf)', before, resuming, in, umbo, larvae, '(', 120, &, 'nbsp;hpf)'])]). relacion([sujeto(['These', results, demonstrated, that, 'Cg-SCL', could, be, used, as, haematopoietic, specific, marker, to, trace, potential, developmental, events, of, hematopoiesis, during, ontogenesis, of, 'oyster,', which, occurred, early, in, blastula, stage, and]), verbo([maintained]), complemento([until, 'D-veliger', larvae])]). relacion([sujeto(['The', current, 'World', 'Health', 'Organization', classification]), verbo([recognizes]), complemento([3, subtypes, of, breast, carcinomas, with, neuroendocrine, features])]). relacion([sujeto(['Their']), verbo([reported]), complemento([prevalence, is, highly, 'variable,', ranging, from, &, 'lt;1%', to, up, to, 20, '%', of, all, breast, carcinomas])]). relacion([sujeto(['We']), verbo([report]), complemento([the, case, of, a, 73, -, 'year-old', woman, who, underwent, lumpectomy, with, a, postoperative, diagnosis, of, invasive, ductal, breast, carcinoma])]). relacion([sujeto(['On', review, of, the, lumpectomy, 'specimen,', a, significant, neuroendocrine, component, was, 'found,']), verbo([leading]), complemento([to, the, final, diagnosis, of, breast, carcinoma, with, neuroendocrine, features, metastasizing, to, the, pancreas])]). relacion([sujeto(['Hence,', metastases, from, breast, carcinomas, with, unrecognized, neuroendocrine, features, may]), verbo([lead]), complemento([to, false, diagnoses, of, primary, neuroendocrine, tumors, at, different, metastatic, 'sites,', such, as, the, pancreas])]). relacion([sujeto(['We', performed, whole, exome, and]), verbo([targeted]), complemento([sequencing, of, 29, 'micropapillary,', 23, 'metaplastic,', and, 27, pleomorphic, lobular, 'BCs'])]). relacion([sujeto(['Metaplastic', 'BCs', presented, a, high, frequency, of, 'TP53', '(', 78, '%', ')', and, 'PIK3CA', '(', 48, '%', ')', mutations, and, were, recurrently, mutated, on, 'KDM6A', '(', 13, '%', ')', ',', a, gene]), verbo([involved]), complemento([in, histone, demethylation])]). relacion([sujeto(['Pleomorphic', lobular, carcinoma, exhibited, high, mutation, rate, of, 'PIK3CA', '(', 30, '%', ')', ',', 'TP53', '(', 22, '%', ')', ',', and, 'CDH1', '(', 41, '%', ')', and, also, presented, mutations, in, 'PYGM,', a, gene]), verbo([involved]), complemento([in, glycogen, 'metabolism,', in, 8, out, of, 27, samples, '(', 30, '%', ')'])]). relacion([sujeto(['(', 1, ')', 'Compared', with, those, in, sham, injury, group, immediately, after, 'injury,', the, percentages, of, 'Th1', and, 'Th2', and, the, ratio, of, 'Th1', to, 'Th2', of, mice, in, burn, group, were, significantly]), verbo([decreased]), complemento([from, 'PIH', 24, 'on,', with, 'P', values, below, 0.05, ;, the, percentages, of, 'Th1', and, 'Th2', and, the, ratios, of, 'Th1', to, 'Th2', of, mice, in, sepsis, group, and, 'burn+', sepsis, group, were, significantly, decreased, from, 'PIH', 12, 'on,', with, 'P', values, below, 0.05])]). relacion([sujeto(['(', 2, ')', 'Compared', with, those, in, sham, injury, group, immediately, after, 'injury,', the, mRNA, expression, levels, of, 'ANXA1', and, 'GATA-3', in, lymphocyte, of, mice, in, burn, group, were, significantly]), verbo([decreased]), complemento([from, 'PIH', 24, 'on,', with, 'P', values, below, 0.05, ;, the, mRNA, expression, level, of, 'T-bet', was, significantly, decreased, at, 'PIH', 24, but, significantly, increased, at, 'PIH', 48, and, 72, ',', with, 'P', values, below, 0.05])]). relacion([sujeto(['Compared', with, those, in, sham, injury, group, immediately, after, 'injury,', the, mRNA, expression, levels, of, 'ANXA1', and, 'GATA-3', in, lymphocytes, of, mice, in, sepsis, group, were, significantly]), verbo([decreased]), complemento([from, 'PIH', 12, 'on,', and, the, mRNA, expression, level, of, 'T-bet', was, increased, significantly, from, 'PIH', 12, 'on,', with, 'P', values, below, 0.05, ;, the, mRNA, expression, levels, of, 'ANXA1,', 'GATA-3,', and, 'T-bet', in, lymphocytes, of, mice, in, 'burn+', sepsis, group, were, significantly, decreased, from, 'PIH', 12, 'on,', with, 'P', values, below, 0.05, ',', reaching, the, nadir, at, 'PIH', 72, '(', 0.5, '±0'])]). relacion([sujeto(['(', 4, ')', 'Compared', with, those, in, sham, injury, group, immediately, after, 'injury,', the, percentages, of, 'ANXA1', and, 'GATA-3', positive, cellsin, 'Th1', and, 'Th2', of, mice, in, burn, group, were, significantly, lowered, from, 'PIH', 24, 'on,', and, the, percentage, of, 'T-bet', positive, cells, was, significantly]), verbo([decreased]), complemento([at, 'PIH', 24, ',', but, it, was, increased, from, 'PIH', 48, 'on,', with, 'P', values, below, 0.05])]). relacion([sujeto(['The', percentages, of, 'ANXA1', and, 'GATA-3', positive, cells, in, 'Th1', and, 'Th2', of, mice, in, sepsis, group, were, continuously]), verbo([decreased]), complemento([from, 'PIH', 12, 'on,', which, were, lower, at, most, time, points, than, those, in, sham, injury, group, immediately, after, 'injury,', with, 'P', values, below, 0.05])]). relacion([sujeto(['The', percentages, of, 'T-bet', positive, cells, in, 'Th1', and, 'Th2', of, mice, in, sepsis, group, were, significantly]), verbo([increased]), complemento([since, 'PIH', 12, as, compared, with, those, in, sham, injury, group, immediately, after, 'injury,', with, 'P', values, below, 0.05])]). relacion([sujeto(['Resistance', is]), verbo([mediated]), complemento([largely, by, a, 'Th2', response, and, 'IgA', and, 'IgE', 'antibodies,', and, is, a, heritable, characteristic])]). relacion([sujeto(['The', polarization, of, 'T', cells, and, the, development, of, appropriate, immune, responses, is, controlled, by, the, master, 'regulators,', 'T-bet', '(', 'TBX21),', 'GATA-3', '(', 'GATA3),', 'RORγt', '(', 'RORC2)', and, 'RORα', '(', 'RORA);', and, several, inflammatory, diseases, of, humans, and, mice, are]), verbo([associated]), complemento([with, allelic, or, transcript, variants, of, these, transcription, factors])]). relacion([sujeto([circumcincta, is]), verbo([associated]), complemento([with, variations, in, the, 'structure,', sequence, or, expression, levels, of, individual, master, regulator, transcripts])]). relacion([sujeto(['We']), verbo([have]), complemento([identified, and, sequenced, one, variant, of, sheep, 'TBX21,', two, variants, of, 'GATA3', and, 'RORC2', and, five, variants, of, 'RORA', from, lymph, node, mRNA])]). relacion([sujeto(['Absolute', 'RT-qPCR', on, 29, all, 45, animals, identified, 'RORAv5', as, being, significantly, 'differentially-expressed', '(', p, =, 0.038, ')', 30, between, 'resistant,', intermediate, and, susceptible, 'groups;', 'RORAv2', was, not, 'differentially-', 31]), verbo([expressed]), complemento(['(', p, =, 0.77, ')'])]). relacion([sujeto(['Exercise']), verbo([induced]), complemento([inflammatory, response, in, 'SLE', remains, to, be, fully, elucidated])]). relacion([sujeto(['In', all, 'groups,', a, single, bout, of, acute, exercise]), verbo([led]), complemento([to, the, 'down-regulation', of, the, gene, expression, of, innate, and, adaptive, immunity, at, the, end, of, exercise, '(', e])]). relacion([sujeto(['Exercise']), verbo([regulated]), complemento([the, expression, of, inflammatory, genes, in, the, blood, leukocytes, of, the, 'SLE', patients, and, 'HC,', although, the, 'SLE', groups, exhibited, fewer, modulated, genes, and, less, densely, connected, networks, '(', number, of, 'nodes:', 29, ',', 40, and, 58, ;, number, of, 'edges:', 29, ',', 60, and, 195, ;, network, 'density:', 0.07, ',', 0.08, and, 0.12, ',', for, 'SLEACTIVE,', 'SLEINACTIVE', and, 'HC,', 'respectively)'])]). relacion([sujeto(['Furthermore,', less, organized, gene, networks, were, observed, in, the, 'SLE', 'patients,']), verbo([suggesting]), complemento([that, they, may, be, deficient, in, triggering, a, normal, 'exercised-induced', immune, transcriptional, response])]). relacion([sujeto(['Craniofacial', microsomia, '(', 'CFM)', is, a, rare, congenital, anomaly, that]), verbo([involves]), complemento([immature, derivatives, from, the, first, and, second, pharyngeal, arches])]). relacion([sujeto(['After', genotyping, of, an, additional, 443, cases, and, 1, ',', 669, 'controls,', we, identify, 8, significantly]), verbo([associated]), complemento([loci, with, the, most, significant, 'SNP', rs13089920, '(', logistic, regression, 'P=2'])]). relacion([sujeto(['The', above, 13]), verbo([associated]), complemento(['loci,', harboured, by, candidates, of, 'ROBO1,', 'GATA3,', 'GBX2,', 'FGF3,', 'NRP2,', 'EDNRB,', 'SHROOM3,', 'SEMA7A,', 'PLCD3,', 'KLF12', and, 'EPAS1,', are, found, to, be, enriched, for, genes, involved, in, neural, crest, cell, '(', 'NCC)', development, and, vasculogenesis])]). relacion([sujeto(['We', then, perform, 'whole-genome', sequencing, on, 21, samples, from, the, case, 'cohort,', and, identify, several, novel, 'loss-of-function', mutations, within, the]), verbo([associated]), complemento([loci])]). relacion([sujeto(['Our', results]), verbo([provide]), complemento([new, insights, into, genetic, background, of, craniofacial, microsomia])]). relacion([sujeto(['The', frequency, of, breast, cancer, in, men, is, extremely, 'rare,']), verbo([reported]), complemento([to, be, less, than, 1, '%', and, there, is, currently, no, available, animal, model, for, male, mammary, tumors])]). relacion([sujeto(['We', compared, the, characteristics, of, various, immunohistochemical, markers, in, 'N-methyl-N-nitrosourea', '(', 'MNU)-induced', mammary, adenocarcinomas, in, male, and, female, 'Crj:CD(SD)IGS', rats, 'including:', estrogen, receptor, α, '(', 'ER),', progesterone, receptor, '(', 'PgR),', androgen, receptor, '(', 'AR),', receptor, 'tyrosine-protein', kinase, 'erbB-2', '(', 'HER2),', 'GATA']), verbo([binding]), complemento([protein, 3, '(', 'GATA3),', and, proliferating, cell, nuclear, antigen, '(', 'PCNA)'])]). relacion([sujeto(['Female', mammary, adenocarcinomas, were, strongly, positive, in, the, nuclei, of, tumor, cells, for, 'PCNA', and, 'ER', '(', 100, '%', ')', with, only, 60, '%', and, 53, '%']), verbo([expressing]), complemento(['PgR', and, 'GATA3,', respectively])]). relacion([sujeto([100, '%', of, male, adenocarcinomas, also, exhibited, strongly, positive, expression, in, the, nuclei, of, tumor, cells, for, 'PCNA,', with, 25, '%']), verbo([expressing]), complemento(['AR', and, only, 8, '%', showing, positivity, for, 'ER'])]). relacion([sujeto(['Male', carcinomas, did, not]), verbo([express]), complemento(['PgR', or, 'GATA3', and, none, of, the, 'tumors,', male, or, 'female,', were, positive, for, 'HER2'])]). relacion([sujeto(['In', 'contrast,', 'MNU-induced', mammary, adenocarcinomas, in, male, rats, showed, no, reactivity, for, 'ER,', 'PgR,', 'HER2', or, 'GATA3,']), verbo([suggesting]), complemento([no, hormonal, dependency])]). relacion([sujeto(['Penile', clear, cell, carcinoma, originating, in, skin, adnexal, glands]), verbo([has]), complemento([been, previously, reported])]). relacion([sujeto(['Tumors', were, large, and]), verbo([involved]), complemento([the, glans, and, coronal, sulcus, in, all, cases])]). relacion([sujeto(['The', 'T', helper, type, 2, '(', 'Th2)', locus, control, region, '(', 'LCR)']), verbo([regulates]), complemento(['Th2', cell, differentiation])]). relacion([sujeto(['Several', transcription, factors]), verbo([bind]), complemento([to, the, 'LCR', to, modulate, the, expression, of, 'Th2', cytokine, 'genes,', but, the, molecular, mechanisms, behind, 'Th2', cytokine, gene, regulation, are, incompletely, understood])]). relacion([sujeto(['Here,', we, used, database, analysis, and, an, oligonucleotide, 'competition/electrophoretic', mobility, shift, assays, to, search, for, transcription, factors]), verbo([binding]), complemento([to, 'RHS5,', a, 'DNase', 'I', hypersensitive, site, '(', 'DHS)', within, the, 'Th2', 'LCR'])]). relacion([sujeto(['Consequently,', we, demonstrated, that, 'GATA-binding', 'protein-3', '(', 'GATA-3),', 'E26', 'transformation-specific', protein, 1, '(', 'Ets-1),', octamer, transcription, 'factor-1', '(', 'Oct-1),', and, 'Oct-2', selectively]), verbo([associate]), complemento([with, 'RHS5'])]). relacion([sujeto(['Furthermore,', chromatin, immunoprecipitation, and, luciferase, reporter, assays, showed, that, 'Oct-1', and, 'Oct-2']), verbo([bound]), complemento([within, the, 'Il4', promoter, region, and, the, 'Th2', 'LCR,', and, that, 'Oct-1', and, 'GATA-3', or, 'Oct-2', synergistically, triggered, the, transactivational, activity, of, the, 'Il4', promoter, through, 'RHS5'])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, 'Oct-1', and, 'GATA-3/Oct-2', direct, 'Th2', cytokine, gene, expression, in, a, cooperative, manner])]). relacion([sujeto(['Considerable', progress]), verbo([has]), complemento([been, made, in, understanding, the, mechanisms, that, control, the, production, of, specialized, neuronal, types])]). relacion([sujeto(['Coordinated', repression, of, gene, expression, by, evolutionarily]), verbo([conserved]), complemento([microRNA, '(', 'miRNA)', clusters, and, paralogs, ensures, that, miRNAs, efficiently, exert, their, biological, impact])]). relacion([sujeto(['Combining', both, 'loss-', and, 'gain-of-function', genetic, 'approaches,', we, show, that, the, 'miR-23∼27∼24', clusters]), verbo([regulate]), complemento([multiple, aspects, of, 'T', cell, 'biology,', particularly, helper, 'T', '(', 'Th)', 2, immunity])]). relacion([sujeto(['Low', expression, of, this, miRNA, family]), verbo([confers]), complemento([proper, effector, 'T', cell, function, at, both, physiological, and, pathological, settings])]). relacion([sujeto(['Further', studies, in, 'T', cells, with, exaggerated, regulation, by, individual, members, of, the, 'miR-23∼27∼24', clusters, revealed, that, 'miR-24', and, 'miR-27', collaboratively, limit, 'Th2', responses, through]), verbo([targeting]), complemento(['IL-4', and, 'GATA3', in, both, direct, and, indirect, manners])]). relacion([sujeto(['Intriguingly,', although, overexpression, of, the, entire, 'miR-23', cluster, also, negatively, impacts, other, 'Th', 'lineages,', enforced, expression, of, 'miR-24,', in, contrast, to, 'miR-23', and, 'miR-27,', actually]), verbo([promotes]), complemento([the, differentiation, of, 'Th1,', 'Th17,', and, induced, regulatory, 'T', 'cells,', implying, that, under, certain, 'conditions,', miRNA, families, can, fine, tune, the, biological, effects, of, their, regulation, by, having, individual, members, antagonize, rather, than, cooperate, with, each, other])]). relacion([sujeto(['Together,', our, results, identify, a, miRNA, family, with, important, immunological, roles, and]), verbo([suggest]), complemento([that, tight, regulation, of, 'miR-23∼27∼24', clusters, in, 'T', cells, is, required, to, maintain, optimal, effector, function, and, to, prevent, aberrant, immune, responses])]). relacion([sujeto(['We', examined, whether, 'CGRP']), verbo([regulates]), complemento([the, outcome, of, 'Ag', presentation, by, 'Langerhans', cells, '(', 'LCs)', to, 'T', cells, through, actions, on, microvascular, endothelial, cells, '(', 'ECs)'])]). relacion([sujeto(['Exposure', of, primary, murine, dermal, microvascular, 'ECs', '(', 'pDMECs)', to, 'CGRP', followed, by, coculture, with, 'LCs,', responsive, 'CD4(+)', 'T', cells, and, 'Ag', resulted, in]), verbo([increased]), complemento([production, of, 'IL-6', and, 'IL-17A', accompanied, by, inhibition, of, 'IFN-γ,', 'IL-4,', and, 'IL-22', compared, with, wells, containing, pDMECs, treated, with, medium, alone])]). relacion([sujeto(['Physical', contact, between, 'ECs', and, 'LCs', or, 'T', cells, was, not]), verbo([required]), complemento([for, this, effect, 'and,', except, for, 'IL-4,', we, demonstrated, that, 'IL-6', production, by, 'CGRP-treated', pDMECs, was, involved, in, these, effects])]). relacion([sujeto(['CD4(+)', cells]), verbo([expressing]), complemento([cytoplasmic, 'IL-17A', were, 'increased,', whereas, cells, expressing, cytoplasmic, 'IFN-γ', or, 'IL-4', were, decreased, by, the, presence, of, 'CGRP-treated', pDMECs])]). relacion([sujeto(['Immunization', at, the, site, of, intradermally, administered, 'CGRP']), verbo([led]), complemento([to, a, similar, bias, in, 'CD4(+)', 'T', cells, from, draining, lymph, node, cells, toward, 'IL-17A', and, away, from, 'IFN-γ'])]). relacion([sujeto(['Actions', of, 'nerve-derived', 'CGRP', on, 'ECs', may]), verbo([have]), complemento([important, regulatory, effects, on, the, outcome, of, 'Ag', presentation, with, consequences, for, the, expression, of, inflammatory, skin, disorders, involving, 'Th17', cells])]). relacion([sujeto(['Breast', 'cancer,', one, of, the]), verbo([leading]), complemento([causes, of, mortality, and, morbidity, among, 'females,', is, regulated, in, part, by, diverse, classes, of, adhesion, molecules, one, of, which, is, known, as, cadherins])]). relacion([sujeto(['Cadherins', possess, diverse, structures, and, functions, and, any, alteration, in, their, structures, or, functions]), verbo([causes]), complemento([impeding, of, normal, mammary, cells, development, and, 'maintenance,', thus, leading, to, breast, malignancy])]). relacion([sujeto(['E-,', 'N-,', 'P-,', 'VE-,', 'Proto-,', desmosomal, and, 'FAT', cadherins]), verbo([have]), complemento([been, found, to, regulate, breast, cancer, in, positive, as, well, as, negative, 'fashion,', whereby, both, 'Ecadherin', '(', 'CDH1)', and, 'N-cadherin', '(', 'CDH2)', contribute, significantly, towards, transitioning, from, epithelial, state, to, mesenchymal, state, '(', 'EMT)', and, enacting, the, abnormal, cells, to, invade, and, metastasize, nearby, and, distant, tissues])]). relacion([sujeto(['Besides', other, 'cadherins,', 'E-cadherin', which, serves, as, hallmark, of, 'EMT', is]), verbo([associated]), complemento([with, several, regulatory, factors, such, as, 'Snail,', 'Slug,', 'Twist,', 'Zeb,', 'KLF4,', 'NFI,', 'TBX2,', 'SIX,', 'b-Myb,', 'COX-2,', 'Arf6,', 'FOXA2,', 'GATA3', and, 'SMAR1,', which, modulate, 'E-cadherin', gene, transcription, to, promote, or, represses, tumor, invasion, and, colonization])]). relacion([sujeto(['Thus,', interactions, of, cadherins, with, their, roles, in, tumor, suppression, and, oncogenic, transformation, can, be, beneficial, in]), verbo([providing]), complemento([valuable, insights, for, breast, cancer, diagnosis, and, therapeutics, development])]). relacion([sujeto(['On', the, other, 'hand,', vast, majority, of, studies, on, 'MycN']), verbo([have]), complemento([been, conducted, in, human, tumor, 'cells,', 'thus,', the, role, of, 'MycN', in, normal, human, neural, crest, development, is, completely, unknown])]). relacion([sujeto(['For', the, first, 'time,', we, show, that, suppression, of, 'MycN', in, hNCSCs]), verbo([inhibits]), complemento([cell, growth, and, cell, cycle, progression])]). relacion([sujeto(['Knockdown', of, 'MycN', in, hNCSCs]), verbo([increases]), complemento([the, expression, of, 'Cdkn1a,', 'Cdkn2a', and, 'Cdkn2b,', which, encodes, the, 'cyclin-dependent', kinases, 'p21CIP1,', p16, 'INK4a', and, p15INK4b])]). relacion([sujeto(['In', 'addition,', 'MycN', is]), verbo([involved]), complemento([in, the, regulation, of, human, sympathetic, 'neurogenesis,', as, knockdown, of, 'MycN', enhances, the, expression, of, key, transcription, factors, involved, in, sympathetic, neuron, 'differentiation,', including, 'Phox2a,', 'Phox2b,', 'Mash1,', 'Hand2', and, 'Gata3'])]). relacion([sujeto(['We', propose, that, unlimited, source, of, hNCSCs]), verbo([provides]), complemento([an, invaluable, platform, for, the, studies, of, human, neural, crest, development, and, diseases])]). relacion([sujeto(['The', transcription, factor, 'GATA3', is, essential, for, the, genesis, and, maturation, of, the, 'T', cell, 'lineage,', and, 'GATA3', dysregulation]), verbo([has]), complemento([pathological, consequences])]). relacion([sujeto(['Previous', studies]), verbo([have]), complemento([shown, that, 'GATA3', function, in, 'T', cell, development, is, regulated, by, multiple, signaling, pathways, and, that, the, 'Notch', nuclear, 'effector,', 'RBP-J,', binds, specifically, to, the, 'Gata3', promoter])]). relacion([sujeto(['We', previously, identified, a, 'T', 'cell-specific', 'Gata3', enhancer, '(', 'Tce1)', lying, 280, kb, downstream, from, the, structural, gene, and, demonstrated, in, transgenic, mice, that, 'Tce1']), verbo([promoted]), complemento(['T', 'lymphocyte-specific', transcription, of, reporter, genes, throughout, 'T', cell, 'development;', 'however,', it, was, not, clear, if, 'Tce1', is, required, for, 'Gata3', transcription, in, vivo])]). relacion([sujeto(['Here,', we, determined, that, the, canonical, 'Gata3', promoter, is, insufficient, for, 'Gata3', transcriptional, activation, in, 'T', cells, in, 'vivo,', precluding, the, possibility, that, promoter]), verbo([binding]), complemento([by, a, host, of, previously, implicated, transcription, factors, alone, is, responsible, for, 'Gata3', expression, in, 'T', cells])]). relacion([sujeto(['Instead,', we, demonstrated, that, multiple, 'lineage-affiliated', transcription, factors]), verbo([bind]), complemento([to, 'Tce1', and, that, this, enhancer, confers, 'T', 'lymphocyte-specific', 'Gata3', activation, in, 'vivo,', as, targeted, deletion, of, 'Tce1', in, a, mouse, model, abrogated, critical, functions, of, this, 'T', 'cell-regulatory', element])]). relacion([sujeto(['Although', the, skin, constitutes, the, first, line, of, defense, against, waterborne, 'pathogens,', there, is, a, great, lack, of, information, regarding, the, skin]), verbo([associated]), complemento([lymphoid, tissue, '(', 'SALT)', and, whether, immune, components, of, the, skin, are, homogeneously, distributed, through, the, surface, of, the, fish, is, still, unknown])]). relacion([sujeto(['In', the, current, 'work,', we]), verbo([have]), complemento([analyzed, the, transcription, of, several, immune, genes, throughout, different, rainbow, trout, '(', 'Oncorhynchus', 'mykiss)', skin, areas])]). relacion([sujeto(['We']), verbo([found]), complemento([that, immunoglobulin, and, chemokine, gene, transcription, levels, were, higher, in, a, skin, area, close, to, the, gills])]). relacion([sujeto(['Furthermore,', this, skin, area, as, well, as, other, anterior, sections, also]), verbo([transcribed]), complemento([significantly, higher, levels, of, many, different, immune, genes, related, to, 'T', cell, immunity, such, as, 'T', cell, receptor, α, '(', 'TCRα),', 'TCRγ,', 'CD3,', 'CD4,', 'CD8,', 'perforin,', 'GATA3,', 'Tbet,', 'FoxP3,', interferon, γ, '(', 'IFNγ),', 'CD40L', and, 'Eomes', in, comparison, to, posterior, skin, sections])]). relacion([sujeto(['We']), verbo([found]), complemento([that, 'VHSV', regulated, the, transcription, of, several, of, these, 'T', cell, markers, in, both, the, skin, and, the, 'spleen;', with, some, differences, between, anterior, and, posterior, skin, sections])]). relacion([sujeto(['Host', genetic, risk, factors]), verbo([have]), complemento([been, successfully, associated, to, leprosy])]). relacion([sujeto(['The', 'A', allele, of, rs10905284, marker, was]), verbo([associated]), complemento([with, leprosy, resistance])]). relacion([sujeto(['Then,', a, functional, analysis, was, conducted, and, showed, that, individuals, carrying, 'AA', genotype]), verbo([express]), complemento([higher, levels, of, 'GATA-3', protein, in, lymphocytes])]). relacion([sujeto(['So,', we, confirmed, that, the, rs10905284, is, a, locus]), verbo([associated]), complemento([to, leprosy, and, influences, the, levels, of, this, transcription, factor, in, the, 'Brazilian', population])]). relacion([sujeto(['Transcripts', of, 'CD33,', 'CD53,', 'CD82,', 'CD205,', macrophage, colony]), verbo([stimulating]), complemento([factor, 'receptor,', 'GATA2,', and, 'GATA3', that, are, specific, for, leucocytes, or, 'monocytes/macrophages', or, both, were, detected, in, the, 'THK', cells, through, 'PCR'])]). relacion([sujeto(['PCR', revealed, that, the, 'THK', cells, exhibited, the, transcripts, of, 'toll-like', receptor, 1, '(', 'TLR1),', 'TLR2,', 'TLR3,', and, 'CD200,', of, which, concern, with, immunity, as, well, as, the, transcripts, of, vascular, endothelial, growth, factor, receptor, 3, ',', 'angiomotin,', and, 'angiopoietin-like', protein, 2, that]), verbo([associate]), complemento([with, angiogenesis, regulation, and, macrophage, proliferation])]). relacion([sujeto(['We']), verbo([report]), complemento([the, first, detailed, case, of, hypoparathyroidism, complicated, by, biliary, atresia])]). relacion([sujeto(['We', suspected, that, this, patient, and, her, mother]), verbo([have]), complemento(['hypoparathyroidism,', sensorineural, 'deafness,', and, renal, dysplasia, syndrome])]). relacion([sujeto([736, 'delGinsAT)', was]), verbo([found]), complemento([in, this, patient, and, her, 'mother,', but, not, in, her, father])]). relacion([sujeto(['Regardless', of, marked, vitamin, 'D', 'deficiency,', the, complication, of, hypoparathyroidism]), verbo([prevented]), complemento([the, onset, of, vitamin, 'D', deficiency, rickets, in, our, patient])]). relacion([sujeto(['Flow', cytometry, '(', 'FCM)', studies, revealed, that, 'ES', substantially]), verbo([inhibited]), complemento(['Th17', 'cells\'', percentage])]). relacion([sujeto(['These', findings]), verbo([suggested]), complemento([that, 'ES', might, effectively, ameliorate, the, progression, of, asthma, and, could, be, used, as, a, therapy, for, patients, with, allergic, asthma])]). relacion([sujeto(['Although', many, studies]), verbo([have]), complemento([implicated, the, crosstalk, between, the, 'Wnt', and, 'PKC', signaling, pathways, in, tumor, initiation, and, 'progression,', the, molecular, roles, of, 'PKC', isoforms, in, the, 'Wnt', signaling, pathway, remain, poorly, understood])]). relacion([sujeto(['In', this, 'study,', we, explored, the, contribution, of, 'PKC', isoforms, to, canonical, and, noncanonical, 'Wnt', signaling, pathway, in]), verbo([mediating]), complemento([cell, migration, and, an, 'epithelial-mesenchymal', transition, '(', 'EMT)'])]). relacion([sujeto(['The', short, term, exposure, '(', 3, 'days)', of, 'MCF-7', cells, to, 'TPA', exhibited, significant, induction, of, 'Wnt5a', 'expression,', along, with, the]), verbo([enhanced]), complemento([expression, of, 'PKC-α,', to, promote, cell, 'migration,', which, suggested, that, activation, of, noncanonical, 'Wnt', signaling, pathway, is, associated, with, 'PKC-α'])]). relacion([sujeto(['However,', the, chronic, exposure, '(', 3, 'weeks)', of, cells, to, 'TPA', completely]), verbo([suppressed]), complemento(['Wnt5a', expression, and, the, expression, of, 'PKC-η', and, 'PKC-δ,', whereas, the, expression, of, 'Wnt3a', and, 'PKC-θ', were, 'up-regulated', to, activate, the, canonical, 'Wnt', signaling, pathway])]). relacion([sujeto(['Moreover,', the]), verbo([loss]), complemento([of, epithelial, 'markers,', including, 'E-cadherin', and, 'GATA-3,', suggested, that, chronic, exposure, of, 'TPA', stimulates, 'EMT'])]). relacion([sujeto(['Taken', 'together,', our, data]), verbo([suggest]), complemento([that, 'PKC-θ', positively, regulates, the, canonical, 'Wnt', signaling, 'pathway,', and, that, 'PKC-η', and, 'PKC-δ', negatively, modulate, this, signaling, pathway])]). relacion([sujeto(['Epigenetic', mechanisms, comprise, a, set, of, biochemical, reactions, that]), verbo([regulate]), complemento([gene, expression])]). relacion([sujeto(['Our', 'ChIP', assay, was, validated, for, a, minimum, requirement, of, 1, ×, 105]), verbo([target]), complemento([cells, '(', e])]). relacion([sujeto(['Very', high, levels, of, maternal, folate, were, significantly]), verbo([associated]), complemento([with, increased, 'H3/H4', acetylation, at, 'GATA3', 'and/or', 'IL9', promoter, regions, in, 'CD4+', 'T', cells, in, 'CB'])]). relacion([sujeto(['Practical', application, of, this, assay, demonstrated, an, association, between, high, maternal, folate, exposure, and]), verbo([increased]), complemento([histone, 'acetylation,', corresponding, to, a, more, transcriptionally, permissive, chromatin, status, in, the, promoter, regions, of, some, 'Th2-related', genes])]). relacion([sujeto(['Hypoparathyroidism,', 'deafness,', and, renal, dysplasia, '(', 'HDR;', 'OMIM', 146255, ')', syndrome, is, a, rare, 'disease,', inherited, dominantly, and]), verbo([found]), complemento([to, be, related, with, 'GATA3', '(', 'GATA', binding, protein, 3, ')', gene, mutations])]). relacion([sujeto(['His', cranial, computed, tomography, revealed, multiple, calcifications, in, bilateral, centrum, 'semiovale,', corona, 'radiata,', and, basal, ganglions]), verbo([suggesting]), complemento([a, persistent, hypoparathyroidism])]). relacion([sujeto(['This', is, the, second, patient, who, was]), verbo([reported]), complemento([to, have, a, mutation, in, 'GATA3', gene, from, 'Turkey'])]). relacion([sujeto(['Bone', 'marrow-derived', 'monocyte-to-fibroblast', transition, is, a, key, step, in, renal, fibrosis, 'pathogenesis,', which, is]), verbo([regulated]), complemento([by, the, inflammatory, microenvironment])]). relacion([sujeto(['However,', the, mechanism, by, which, the, inflammatory, microenvironment]), verbo([regulates]), complemento([this, transition, is, not, fully, understood])]). relacion([sujeto(['In', this, 'study,', we, examined, how, the, 'CD8(+)', 'T', 'cell/IFN-γ', microenvironment]), verbo([regulates]), complemento([the, 'monocyte-to-fibroblast', transition, in, renal, fibrosis])]). relacion([sujeto(['Genetic', ablation, of, 'CD8']), verbo([promoted]), complemento([a, 'monocyte-to-fibroblast', transition, and, increased, renal, interstitial, 'fibrosis,', whereas, reconstitution, of, 'CD8', knockout, '(', 'KO)', mice, with, 'CD8(+)', 'T', cells, decreased, fibrosis])]). relacion([sujeto(['To', elucidate, the, role, of, 'CD4(+)', 'T', cells, in]), verbo([mediating]), complemento(['CD8-regulated', 'monocyte-to-fibroblast', 'transition,', 'CD4(+)', 'T', cells, were, isolated, from, obstructed, kidneys, of, 'CD8', 'KO', or, 'wild-type', mice])]). relacion([sujeto(['CD4(+)', 'T', cells, isolated, from, 'CD8', 'KO', obstructed, kidney]), verbo([expressed]), complemento([more, 'IL-4', and, 'GATA3', and, less, 'IFN-γ', and, 'T-bet', and, showed, increased, 'monocyte-to-fibroblast', transition, in, vitro, compared, with, those, isolated, from, 'wild-type', obstructed, kidney])]). relacion([sujeto(['Taken', 'together,', our, findings, identify, the, axis, of, 'CD8(+)', 'T', cells, and, 'IFN-γ-CD4(+)', 'T', cells, as, an, important, microenvironment, for, the, 'monocyte-to-fibroblast', 'transition,', which, negatively]), verbo([regulates]), complemento([renal, fibrosis])]). relacion([sujeto(['Although', the, developmental, program]), verbo([leading]), complemento([to, mature, 'NK', cells, has, been, studied, in, the, context, of, several, transcription, 'factors,', the, 'stage-specific', role, of, 'GATA3', in, 'NK', cell, development, has, been, incompletely, understood])]). relacion([sujeto(['Using', 'NKp46-Cre-Gata3(fl/fl)', mice, in, which, 'Gata3', deficiency, was]), verbo([induced]), complemento([as, early, as, the, immature, stage, of, 'NK', cell, 'differentiation,', we, demonstrated, that, 'GATA3', is, required, for, the, 'NK', cell, maturation, beyond, the, 'CD27', 'single-positive', stage, and, is, indispensable, for, the, maintenance, of, 'liver-resident', 'NK', cells])]). relacion([sujeto(['The', frequencies, of, 'NK', cells, from, 'NKp46-Cre-Gata3(fl/fl)', mice, were]), verbo([found]), complemento([higher, in, the, 'BM', but, lower, in, peripheral, organs, compared, with, control, 'littermates,', indicating, that, 'GATA3', controls, the, maturation, program, required, for, 'BM', egress])]). relacion([sujeto(['Despite', the, defect, in, 'maturation,', upon, murine, 'CMV', 'infection,', 'NK', cells, from, 'NKp46-Cre-Gata3(fl/fl)', mice, expanded, 'vigorously,', achieving, 'NK', cell, frequencies, surpassing, those, in, controls, and, therefore]), verbo([provided]), complemento([comparable, protection])]). relacion([sujeto(['The', heightened, proliferation, of, 'NK', cells, from, 'NKp46-Cre-Gata3(fl/fl)', mice, was, cell, intrinsic, and]), verbo([associated]), complemento([with, enhanced, upregulation, of, 'CD25', expression])]). relacion([sujeto(['Taken', 'together,', our, results, demonstrate, that, 'GATA3', is, a, critical, regulator, for, 'NK', cell, terminal, maturation, and, egress, out, of, the, 'BM', and, that, immature, 'NK', cells, present, in, the, periphery, of, 'NKp46-Cre-Gata3(fl/fl)', mice, can, rapidly, expand, and]), verbo([provide]), complemento([a, reservoir, of, 'NK', cells, capable, of, mounting, an, efficient, cytotoxic, response, upon, virus, infection])]). relacion([sujeto(['Their', expression]), verbo([has]), complemento([not, been, previously, thoroughly, examined, in, testicular, germ, cell, tumors])]). relacion([sujeto(['The', first, two, are, cytoplasmic, markers, that, show, comparable, sensitivities, for, breast, 'cancer,', although, relatively, few, of, the, published, studies]), verbo([have]), complemento([employed, the, same, antibodies, against, the, target, 'molecule,', making, direct, comparisons, challenging])]). relacion([sujeto(['GATA3', is, a]), verbo([nuclear]), complemento([transcription, factor, that, shows, superior, sensitivity, to, 'GCDFP-15', and, mammaglobin])]). relacion([sujeto(['Immune', 'dysregulation,', 'polyendocrinopathy,', 'enteropathy,', 'X-linked', '(', 'IPEX)', syndrome, is, a, severe, autoimmune, disease, that, is]), verbo([caused]), complemento([by, regulatory, 'T cell', deficiency, due, to, 'FOXP3', gene, mutations])]). relacion([sujeto(['The', 'long-term', outcome, can, be, variable, depending, on, the, extent, of, tissue, damage]), verbo([caused]), complemento([by, autoimmunity, and, 'infections,', the, use, of, immunosuppressive, treatment, or, sequela, of, bone, marrow, transplantation])]). relacion([sujeto(['The', percentages, of, cells]), verbo([expressing]), complemento([the, 'TH2-associated', transcription, factor, 'GATA3', were, higher, in, the, 'IPEX', patient, before, treatment, than, in, 'controls,', suggesting, that, 'TH2-type', cells, contribute, to, the, tissue, inflammation, of, the, gut, and, kidneys, in, 'IPEX', syndrome])]). relacion([sujeto(['Immunosuppressive', treatment, effectively]), verbo([decreased]), complemento([the, number, of, effector, cells, in, the, kidneys, and, intestine, of, the, 'IPEX', patient])]). relacion([sujeto(['This', study]), verbo([provides]), complemento([quantitative, evidence, that, the, inflamed, intestinal, and, renal, tissues, of, the, 'IPEX', patient, contain, 'TH2-type', immune, effector, 'cells,', which, decreased, in, number, after, immunosuppressive, treatment, was, initiated, and, the, clinical, symptoms, had, improved])]). relacion([sujeto(['Protection', of, epithelial, and, mucosal, surfaces, is]), verbo([required]), complemento([for, survival])]). relacion([sujeto(['The', recent, discovery, of, a, diverse, array, of, innate, lymphoid, cells, that, lie, immediately, beneath, these, surfaces]), verbo([has]), complemento([unexpectedly, uncovered, an, entire, defense, system, distinct, from, the, adaptive, system, essential, to, protect, these, barriers])]). relacion([sujeto(['This', multilayered, design]), verbo([provides]), complemento([a, robust, system, through, coupling, of, two, highly, complementary, networks, to, ensure, immune, protection])]). relacion([sujeto(['Human', 'CRTh2(+)', 'Th2', cells]), verbo([express]), complemento(['IL-25', receptor, '(', 'IL-25R)', and, 'IL-25', has, been, shown, to, potentiate, production, of, 'Th2', cytokines])]). relacion([sujeto(['However,', regulation, of, 'IL-25R', and, whether, it]), verbo([participates]), complemento([in, 'Th2', differentiation, of, human, cells, have, not, been, examined])]). relacion([sujeto(['Naïve', human, 'CD4(+)', 'T', cells, were]), verbo([activated]), complemento([in, the, presence, of, 'IL-25,', 'IL-4', '(', 'Th2', 'conditions)', or, both, cytokines, to, assess, their, relative, influence, on, 'Th2', differentiation])]). relacion([sujeto(['Expression', of, surface, 'IL-25R', was]), verbo([induced]), complemento([early, during, 'Th2', differentiation, '(', 2, 'days)'])]). relacion([sujeto(['Addition', of, 'IL-25', to, naïve, 'CD4(+)', 'T', cells, revealed, that, it]), verbo([induces]), complemento([expression, of, its, own, 'receptor,', more, strongly, than, 'IL-4'])]). relacion([sujeto(['IL-25', also]), verbo([increased]), complemento([the, proportions, of, 'IL-4-,', 'GATA3-', and, 'CRTh2-expressing', cells, and, expression, of, 'IL-5', and, 'IL-13'])]). relacion([sujeto(['Activation', of, differentiated, 'CRTh2(+)', 'Th2', cells, through, the, 'TCR', or, by, 'CRTh2', agonist]), verbo([increased]), complemento([surface, expression, of, 'IL-25R,', though, 're-expression', of, 'CRTh2', following, 'TCR', downregulation, was, impeded, by, 'IL-25'])]). relacion([sujeto(['These', data]), verbo([suggest]), complemento([that, 'IL-25', may, play, various, roles, in, 'Th2', mediated, immunity])]). relacion([sujeto(['We', establish, here, it]), verbo([regulates]), complemento([expression, of, its, own, receptor, and, can, initiate, 'Th2', 'differentiation,', though, not, as, strongly, as, 'IL-4'])]). relacion([sujeto(['Appropriate', diagnostic, tests, may, not, be, available, or, available, tests, may, not]), verbo([provide]), complemento([appropriate, coverage, of, relevant, genomic, regions, for, patients, with, complex, phenotypes])]). relacion([sujeto(['At', 6, weeks, of, 'age,']), verbo([he]), complemento([presented, with, failure, to, thrive, and, hypoparathyroidism])]). relacion([sujeto(['At', 4, years, of, 'age,']), verbo([he]), complemento([was, diagnosed, with, sensorineural, hearing, loss])]). relacion([sujeto(['Whole-genome', sequencing, identified, novel, mutations, in, 'GATA3,', which]), verbo([causes]), complemento(['HDR', syndrome, '(', hypoparathyroidism, and, 'deafness),', and, 'STS,', which, causes, 'X', -, linked, congenital, ichthyosis])]). relacion([sujeto(['Whole-genome', sequencing]), verbo([led]), complemento([to, a, definitive, clinical, diagnosis, in, a, case, where, no, other, clinical, test, was, available, for, 'GATA3,', and, no, sequencing, panel, would, have, included, both, genes, because, they, have, disparate, phenotypes])]). relacion([sujeto(['This', case, demonstrates, the, power, of, 'whole-genome', '(', or, 'exome)', sequencing, for, patients, with, complex, clinical, presentations]), verbo([involving]), complemento([endocrine, abnormalities])]). relacion([sujeto(['In', recent, 'years,', 'Dendrobium', candidum]), verbo([has]), complemento([played, a, part, in, antihyperthyroidism, and, anticancer, drugs])]). relacion([sujeto([candidum, significantly]), verbo([decreased]), complemento([cell, viability, at, different, concentrations, compared, to, the, control, group, '(', 'P<0'])]). relacion([sujeto(['candidum-treated', 'MCF-7', cells, in, the, 'G2/M', phase, was, significantly]), verbo([increased]), complemento([compared, to, the, control, group, '(', 'P<0'])]). relacion([sujeto(['The', protein, levels, of, estrogen, receptor, 'alpha,', 'PGR,', 'GATA3,', and, 'Ki67', were, significantly]), verbo([decreased]), complemento([and, the, protein, levels, of, p53, and, 'ELF5', were, significantly, increased, compared, to, the, control, group, '(', 'P<0'])]). relacion([sujeto(['The', general, apoptosis, 'biomarker,', 'Bcl-2,', was, significantly]), verbo([decreased]), complemento([and, the, 'Bax', was, significantly, increased, compared, to, the, control, group, '(', 'P<0'])]). relacion([sujeto([candidum, could]), verbo([decrease]), complemento([the, cell, viability, of, 'MCF-7', cells, by, inducing, cell, cycle, arrest, at, the, 'G2/M', phase, and, regulating, the, key, biomarkers, in, breast, cancer, cells])]). relacion([sujeto(['Genetic', selection, for]), verbo([enhanced]), complemento([immune, response, has, been, shown, to, decrease, disease, occurrence, in, dairy, cattle])]). relacion([sujeto(['Blood', mononuclear, cells, '(', 'BMC)', isolated, from, cows, classified, as, 'H-AMIR', and, 'H-CMIR', through, estimated, breeding, values, for, immune, response, traits, were]), verbo([stimulated]), complemento([with, concanavalin, 'A', '(', 'ConA;', 'Sigma', 'Aldrich,', 'St'])]). relacion([sujeto(['The', 'BMC', from, 'H-CMIR', cows, had]), verbo([increased]), complemento([production, of, 'IFN-γ', protein, at, 48, ',', 72, ',', and, 96, h, compared, with, 'H-AMIR', animals])]). relacion([sujeto(['Further,', 'H-CMIR', cows, had]), verbo([increased]), complemento([expression, of, the, 'IFNG', gene, at, 16, ',', 24, ',', and, 48, h, 'post-treatment', with, 'ConA,', although, expression, of, the, 'type-1', transcription, factor, gene, 'TBX21', did, not, differ, between, immune, response, groups])]). relacion([sujeto(['Although', proliferation, of, 'BMC']), verbo([increased]), complemento([from, 24, to, 72, h, after, 'ConA', 'stimulation,', no, differences, were, found, between, the, immune, response, groups])]). relacion([sujeto(['Hdac9', was, identified, as, a, potential, candidate, for, 'Skts5', based, on]), verbo([conserved]), complemento(['non-synonymous', sequence, variants, and, expression, analyses])]). relacion([sujeto(['NIH/Ola-S', clones, showed, an, approximate, 1.7, -, fold]), verbo([increased]), complemento([luciferase, expression, relative, to, vector, alone, or, the, equivalent, clones, from, 'SPRET/Out-R-R'])]). relacion([sujeto(['Furthermore,', cells, transfected, with, a, portion, of, the, 'NIH/Ola-S', intron]), verbo([induced]), complemento([2.2, -, fold, increases, in, 'Twist1', 'expression,', but, the, same, region, from, 'SPRET/Out-R', mice, resulted, in, no, 'up-regulation', of, 'Twist1'])]). relacion([sujeto(['In', silico, transcription, factor, analyses, identified, multiple, transcription, factors, predicted, to, differentially]), verbo([bind]), complemento(['NIH/Ola-S', and, 'SPRET/Out-R', polymorphic, sites])]). relacion([sujeto(['Chromatin', immunoprecipitation, studies, of, two, transcription, 'factors,', 'Gata3', and, 'Oct1,', demonstrated, differential]), verbo([binding]), complemento([between, 'NIH/Ola-S', and, 'SPRET/Out-R', plasmids, that, corroborated, the, in, silico, predictions])]). relacion([sujeto(['Together', these, studies]), verbo([provide]), complemento([evidence, that, the, murine, orthologous, region, to, a, human, 'HDAC9', enhancer, also, acts, as, a, transcriptional, enhancer, for, mouse, 'Twist1'])]). relacion([sujeto(['GATA3', expression, was]), verbo([associated]), complemento([with, good, prognostic, 'parameters,', but, fascin, was, correlated, with, poor, prognostic, parameters])]). relacion([sujeto(['On', comparing, 'GATA3', and, 'fascin,', we]), verbo([found]), complemento([an, inverse, relationship, between, fascin, and, 'GATA3', expressions])]). relacion([sujeto(['Marked']), verbo([increases]), complemento([in, the, serum, levels, of, 'OVA-specific', 'IgA', 'antibody,', 'IgA', and, 'IgG,', 'C3', deposits, analogous, to, those, seen, in, 'IgAN,', and, expansion, of, the, matrix, in, association, with, mesangial, cell, proliferation, were, observed])]). relacion([sujeto(['Furthermore,', glomerular, 'IgA', deposits, were, 'co-localized', with, 'mannan-binding', lectin, '(', 'MBL)', 'deposits,', which, might, actually]), verbo([have]), complemento([been, abnormal, 'IgA', deposits])]). relacion([sujeto(['In', 'GATA-3/TCR-Tg', mice, that, had, been, orally, sensitized, with, 'CTB', plus, 'OVA', and, were, 're-stimulated', with, 'OVA', in, 'vitro,', cultured, 'Peyer\'s', patch, cells, showed, the]), verbo([enhanced]), complemento([production, of, 'IL-5', and, supernatants, from, cultures, of, spleen, cells, showed, a, reduction, of, 'TGF-β', production, with, a, simultaneous, increase, in, 'IL-2', production, and, the, recovery, of, 'IFN-γ', formation])]). relacion([sujeto(['The', amount, of, 'TGF-β', produced, by, the, spleen, cells, was]), verbo([found]), complemento([to, be, correlated, with, the, amount, of, 'IFN-γ', and, 'IL-IL-2', produced, by, the, cells])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, the, increased, production, of, 'IL-5', from, 'Peyer\'s', patch, cells, '(', 'PPc)', and, the, restored, 'Th1-type', immune, response, might, cause, the, production, of, abnormal, 'IgA', and, might, induce, the, deposition, of, 'IgA', in, glomeruli])]). relacion([sujeto(['We', show, here, that, different, 'GABAergic', and, glutamatergic, subgroups]), verbo([associated]), complemento([with, the, monoaminergic, nuclei, express, specific, transcription, factors])]). relacion([sujeto(['The', syndrome, of, familial, 'hypoparathyroidism,', sensorineural, 'deafness,', and, renal, dysplasia, '(', 'HDR', 'syndrome)', is, inherited, as, an, autosomal, dominant, 'trait,']), verbo([caused]), complemento([by, haploinsufficiency, of, the, 'GATA3', gene, in, chromosome, 10, p])]). relacion([sujeto(['Hearing']), verbo([loss]), complemento([is, usually, 'bilateral,', range, from, mild, to, profound, impairment])]). relacion([sujeto(['The', few, studies, that, evaluate, the, immunological, response, of, 'JLD', patients, show, a, predominance, of, 'Th2', 'response,', as, well, as, a, high, frequency, of, 'TGF-β', and, 'IL-10', positive, cells, in, the, 'lesions;', 'however,', the, overall, immunological, status, of, the, lesions, in, terms, of, their, 'T', cell, phenotype]), verbo([has]), complemento([yet, to, be, determined])]). relacion([sujeto(['The', results, showed, an]), verbo([increased]), complemento([expression, of, 'FoxP3,', 'CTLA4,', 'TGF-β1,', 'IL-10,', 'T-bet,', 'IL-17F,', and, 'IL-17A', in, 'lesions,', while, 'GATA3', and, 'IL-4', levels, were, found, to, be, lower, in, diseased, skin, than, in, the, control, group])]). relacion([sujeto(['When', the, clinical, forms, were, 'compared,', 'TGF-β1', was]), verbo([found]), complemento([to, be, highly, expressed, in, patients, with, a, single, localized, lesion, while, 'IL-5', and, 'IL-17A', levels, were, higher, in, patients, with, 'multiple/disseminated', lesions])]). relacion([sujeto(['These', results, demonstrate, the, occurrence, of, mixed, 'T', helper, responses, and]), verbo([suggest]), complemento([the, dominance, of, regulatory, 'T', cell, 'activity,', which, could, inhibit, 'Th-dependent', protective, responses, to, intracellular, fungi, such, as, 'L'])]). relacion([sujeto(['The', plant, protein, trichosanthin, '(', 'Tk)', and, its, derived, peptide, tetramer, 'Tk-tPN']), verbo([have]), complemento([been, shown, to, stimulate, the, type, 2, immune, responses, for, treating, autoimmune, disease])]). relacion([sujeto(['This', work, explores, the, possibility, of, using, 'Tk-tPN', as, a, 'non-toxic', immunosuppressant, to]), verbo([induce]), complemento([transplantation, tolerance, using, the, mechanisms, by, which, 'T-cell-mediated', immune, responses, are, transferred, from, type, 1, to, type, 2, through, innate, 'immunity-related', pathways])]). relacion([sujeto(['Immunocytes', and, cytokine, secretions]), verbo([involved]), complemento([in, the, mouse, cardiac, allografting, model, with, 'Tk-tPN', treatment, were, characterized])]). relacion([sujeto(['Tk-tPN', could, be, a, promising, novel, immunosuppressant, to]), verbo([induce]), complemento([tolerance, in, allotransplantation])]). relacion([sujeto(['Methamphetamine', '(', 'METH)', is, an, addictive, psychostimulant, and]), verbo([has]), complemento([been, shown, to, induce, oxidative, stress, and, inflammation, in, various, tissues])]). relacion([sujeto(['Thioredoxin-1', '(', 'Trx-1)', plays, the, roles, in]), verbo([regulating]), complemento([redox, and, inhibiting, inflammation])]). relacion([sujeto(['Whether', 'Trx-1', is]), verbo([involved]), complemento([in, 'METH-induced', inflammation, is, still, unknown])]). relacion([sujeto(['We']), verbo([found]), complemento([the, mRNA, level, of, 'Trx-1', was, decreased, and, mRNA, level, of, 'Trx-1', binding, 'protein-2', '(', 'TBP-2)', was, increased])]). relacion([sujeto(['The', mRNA, levels, of, tumor, necrosis, 'factor-α', '(', 'TNF-α),', 'interferon-γ(IFN-γ),', 'interleukin-2', '(', 'IL-2),', 'T-bet', and, signal, transducer, and, activators, of, transcription, 4, '(', 'STAT', 4, ')', were]), verbo([increased]), complemento([and, the, mRNA, levels, of, 'IL-10,', 'GA-TA-binding', 'protein-3', '(', 'GATA-3)', and, 'STAT', 6, were, decreased])]). relacion([sujeto(['Overexpression', of, 'Trx-1', reversed, the, above, effects]), verbo([induced]), complemento([by, 'METH'])]). relacion([sujeto(['The', present, study, showed, for, the, first, time, that, 'Trx-1', overexpression]), verbo([suppressed]), complemento([the, inflammation, induced, by, 'METH'])]). relacion([sujeto(['Previously,', we, observed, that, wild, yam, '(', 'Dioscorea', 'villosa)', root, extract, '(', 'WYRE)', was, able, to]), verbo([activate]), complemento(['GATA3', in, human, breast, cancer, cells, targeting, epigenome])]). relacion([sujeto(['This', study, aimed, to]), verbo([find]), complemento([out, if, dioscin, '(', 'DS),', a, bioactive, compound, of, 'WYRE,', can, modulate, 'GATA3', functions, and, cellular, invasion, in, human, breast, cancer, cells])]). relacion([sujeto(['GATA3', expression, was]), verbo([enhanced]), complemento([by, 'DS', '(', 5.76, 'μM)', in, 'MDA-MB-231', cells])]). relacion([sujeto(['DS', '(', 5.76, 'μM)-treated', 'MDA-MB-231', cells, exhibited, the, morphological, characteristic, of, 'epithelial-like', 'cells;', mRNA, expression, of, 'DNMT3A,', 'TET2,', 'TET3,', 'ZFPM2', and, 'E-cad', were]), verbo([increased]), complemento([while, 'TET1,', 'VIM', and, 'MMP9', were, decreased])]). relacion([sujeto(['Our', data]), verbo([suggested]), complemento([that, 'DS-mediated', pathway, could, promote, 'GATA3', expression, at, transcription, and, translation, levels])]). relacion([sujeto(['We', propose, that, 'DS']), verbo([has]), complemento([potential, to, be, used, as, an, 'anti-invasive', agent, in, breast, cancer])]). relacion([sujeto(['Interleukin', '(', 'IL)-10,', a, 'non-redundant', 'anti-inflammatory', cytokine, is, produced, by, different, cells, and, its, production]), verbo([involves]), complemento([activation, of, 'cell-specific', transcriptional, regulatory, machinery, in, response, to, specific, pathogen])]). relacion([sujeto(['We']), verbo([have]), complemento([previously, demonstrated, downregulated, levels, of, 'IL-10', in, severe, falciparum, malaria])]). relacion([sujeto(['In', 'addition,', a, role, for, 'interferon-α', in]), verbo([suppressing]), complemento(['IL-10', transcription, was, evident, from, its, negative, correlation, with, 'GATA3', and, 'IL-10', levels])]). relacion([sujeto(['In', 'summary,', 'IL-10', transcription, in, 'Th1', and, 'Th2', is, defective, and, appears, to]), verbo([have]), complemento([major, contribution, to, low, levels, in, severe, malaria])]). relacion([sujeto(['Here,', we, develop, a, novel, framework, to, identify, topological, patterns, of, gene, coexpression, network, and, detect, changes, of]), verbo([modular]), complemento([structure, across, different, stages, of, 'HIV', progression])]). relacion([sujeto(['To', capture, the, diversity, in]), verbo([modular]), complemento(['structure,', some, 'topological,', correlation, based, and, eigengene, based, measures, are, utilized, here])]). relacion([sujeto(['We']), verbo([have]), complemento([applied, a, rank, aggregation, scheme, to, rank, all, the, modules, to, provide, a, good, agreement, between, these, measures])]). relacion([sujeto(['Moreover,', we]), verbo([have]), complemento([performed, an, eigengene, based, analysis, to, reveal, the, perturbation, in, modular, structure, across, three, stages, of, 'HIV-1', progression])]). relacion([sujeto(['We', discovered, 285, complex, indels, in, 'cancer-associated', genes, '(', such, as, 'PIK3R1,', 'TP53,', 'ARID1A,', 'GATA3', and, 'KMT2D)', in, approximately, 3.5, '%', of, cases, 'analyzed;', nearly, all, instances, of, complex, indels, were, overlooked, '(', 81.1, '%', ')', or, misannotated, '(', 17.6, '%', ')', in, previous]), verbo([reports]), complemento([of, 2, ',', 199, samples])]). relacion([sujeto(['Atopic', dermatitis, '(', 'AD)', is, a, skin, condition]), verbo([caused]), complemento([by, an, imbalance, of, distinct, subsets, of, 'T', helper, cells])]). relacion([sujeto(['Previously,', we, showed, that, 4, -, 'hydroxy-3-methoxycinnamaldehyde', '(', 4, 'H3MC)']), verbo([inhibits]), complemento(['T', cell, activation, but, does, not, induce, apoptosis])]). relacion([sujeto(['Oral', administration, of, 4, 'H3MC', attenuated, the, symptoms, of, 'DNCB-', and, 'mite-induced', 'AD,', including]), verbo([increased]), complemento([ear, 'thickness,', serum, 'IgE', 'levels,', immune, cell, infiltration, into, inflammatory, 'lesions,', and, pathogenic, cytokine, expression, in, ear, tissues])]). relacion([sujeto(['In', 'vitro,', 4, 'H3MC', blocked, 'T', cell, differentiation, into, 'Th1', and, 'Th2', 'subtypes,', as, reflected, by, suppression, of, 'T-bet', and, 'GATA3,', which, are, key, transcription, factors]), verbo([involved]), complemento([in, 'T', cell, differentiation])]). relacion([sujeto(['Collectively,', these, findings]), verbo([suggest]), complemento([that, 4, 'H3MC', ameliorates, 'AD', symptoms, by, modulating, the, functions, of, effector, 'T', cells, and, keratinocytes])]). relacion([sujeto(['Several', clinical, phenotypes, often]), verbo([leading]), complemento([to, uncontrolled, 'disease,', including, adult, nasal, 'polyposis,', 'aspirin-exacerbated', respiratory, 'disease,', and, allergic, fungal, 'rhinosinusitis,', are, characterized, by, a, common, 'endotype:', a, 'TH2', bias, is, associated, with, a, higher, likelihood, of, comorbid, asthma, and, recurrence, after, surgical, treatment])]). relacion([sujeto(['As', a, 'consequence,', several, innovative, approaches]), verbo([targeting]), complemento([the, 'TH2', bias, with, humanized, mAbs, have, been, subjected, to, 'proof-of-concept', studies, in, patients, with, 'CRS', with, nasal, polyps, with, or, without, comorbid, 'asthma:', 'omalizumab,', 'reslizumab,', 'mepolizumab,', and, recently, dupilumab])]). relacion([sujeto(['The', level, of, immune, factor, 'IL-2', notably]), verbo([increased]), complemento(['(', 'IM,', 121, ±, 9.0, ')', '(', p, &, 'lt;', 0.05, ')', and, was, close, to, 65, '%', of, 'NIM', 'group\'s', level, '(', 230, ±, 10.7, ')'])]). relacion([sujeto(['However,', the, level, of, immune, factor, 'IL-4', remarkably]), verbo([decreased]), complemento(['(', 'IM,', 128, ±, 10.2, ')', '(', p, &, 'lt;', 0.05, ')', and, was, only, approximately, 50, '%', of, the, 'NIM', group, '(', 154, ±, 18.2, ')'])]). relacion([sujeto(['These', findings]), verbo([suggest]), complemento([that, 'L'])]). relacion([sujeto([plantarum, 'NCU116']), verbo([enhanced]), complemento([the, immunity, of, the, small, intestine, in, the, immunosuppressed, mice])]). relacion([sujeto(['Analysis', of, 'ERα', '(', +, ')', breast, cancer, cohort, '(', n, =, 195, ')', showed, high, expression, of, 'GATA3,', 'NTN4,', and, 'MLPH', genes, significantly]), verbo([associated]), complemento([with, longer, 'relapse-free', survival, '(', 'RFS)'])]). relacion([sujeto(['Next', cohort, of, 'ERα', '(', +, ')', and, node, '(', +, ')', samples, '(', n, =, 109, ')', revealed, high, mRNA, expression, of, 'GATA3,', 'SLC7A8,', and, 'MLPH', significantly]), verbo([associated]), complemento([with, longer, 'RFS'])]). relacion([sujeto(['The', validated, 'three-gene', signature, sets, for, 'ERα', '(', +, ')', 'cohort,', and, 'ERα', '(', +, ')', and, node, '(', +, ')', cohort, may]), verbo([have]), complemento([potential, clinical, utility, since, they, demonstrated, predictive, and, prognostic, ability, in, three, independent, public, data, sets])]). relacion([sujeto(['Vaccines', were, composed, of, bone, 'marrow-derived', 'DCs']), verbo([activated]), complemento([with, tumor, cell, lysate, '(', 'BM-DC/TAgTNF-α)', 'and/or', genetically, modified, 'DCs', of, 'JAWS', 'II', line, '(', 'JAWS', 'II/Neo', or, 'JAWS', 'II/IL-2', 'cells)'])]). relacion([sujeto(['Compared', to, untreated, or, 'CY-treated', 'mice,', the, combined, treatment, of, 'MC38', colon, 'carcinoma-bearing', mice, resulted, in, significant, tumor, growth, inhibition]), verbo([associated]), complemento([with, an, increase, in, influx, of, 'CD4+', and, 'CD8+', 'T', cells, into, tumor, tissue])]). relacion([sujeto(['The', administration, of, 'CY', followed, by, 'BM-DC/TAgTNF-α', and, genetically, modified, 'JAWS', 'II', 'cells,']), verbo([increased]), complemento([the, percentage, of, 'CD4+T-bet+', and, 'CD4+GATA3+', cells, and, decreased, the, percentage, of, 'CD4+RORγt+', and, 'CD4+FoxP3+', lymphocytes])]). relacion([sujeto(['GATA3', is, a, highly, 'conserved,', essential, transcription, factor]), verbo([expressed]), complemento([in, a, number, of, 'tissues,', including, the, mammary, gland])]). relacion([sujeto(['GATA3', expression, is]), verbo([required]), complemento([for, normal, development, of, the, mammary, gland, where, it, is, estimated, to, be, the, most, abundant, transcription, factor, in, luminal, epithelial, cells])]). relacion([sujeto(['Recent', genomic, analysis, of, human, breast, cancers]), verbo([has]), complemento([revealed, 'high-frequency', mutation, in, 'GATA3', in, luminal, 'tumors,', suggesting, &, 'quot;driver"', 'function(s)'])]). relacion([sujeto(['Here', we, discuss, mutation, of, 'GATA3', in, breast, cancer, and, the, potential, 'mechanism(s)', by, which, mutation, may]), verbo([lead]), complemento([to, a, growth, advantage, in, cancer])]). relacion([sujeto(['Previous', studies]), verbo([have]), complemento([shown, that, 'BMP4', may, play, an, important, part, in, the, development, of, auditory, neurons, '(', 'ANs),', which, are, degenerated, in, sensorineural, hearing, loss])]). relacion([sujeto(['However,', whether, 'BMP4', can]), verbo([promote]), complemento([sensory, fate, specification, from, mesenchymal, stromal, cells, '(', 'MSCs)', is, unknown, so, far])]). relacion([sujeto(['MSCs', treated, with, a, complex, of, neurotrophic, factors, '(', 'BMP4', group, and, 'non-BMP4', 'group)', were]), verbo([induced]), complemento([into, auditory, 'neuron-like', 'cells,', then, the, differences, between, the, two, groups, were, analyzed, in, morphological, 'observation,', cell, growth, 'curve,', 'qRT-PCR,', and, immunofluorescence])]). relacion([sujeto(['Flow', cytometric, analysis, showed, that, the, isolated, cells]), verbo([expressed]), complemento([typical, 'MSC', surface, markers])]). relacion([sujeto(['The', neuronal]), verbo([induced]), complemento([cells, were, in, the, growth, plateau, and, had, special, forms, of, neurons])]). relacion([sujeto(['MSCs']), verbo([have]), complemento([the, capacity, to, differentiate, into, auditory, 'neuron-like', cells, in, vitro])]). relacion([sujeto(['Oral', administration, of, 'AcRE', and, prednisolone, '(', 'PS)', significantly]), verbo([suppressed]), complemento(['TMA-induced', increases, in, ear, and, epidermal, 'thickness,', and, 'IgE', expression])]). relacion([sujeto(['Treatment', with, 'AcRE', also, significantly]), verbo([suppressed]), complemento(['TMA-induced', 'IL-4', and, 'IL-13', cytokines, and, mRNA, expression, in, vivo])]). relacion([sujeto(['Moreover,', 'AcRE', strongly]), verbo([suppressed]), complemento(['TMA-induced', 'IL-4', and, 'IL-5', production, in, draining, lymph, 'nodes,', as, well, as, 'OVA-induced', 'IL-4', and, 'IL-5', expression, in, primary, cultured, splenocytes])]). relacion([sujeto(['Interestingly,', 'AcRE']), verbo([suppressed]), complemento(['IL-4-induced', 'STAT6', phosphorylation, in, both, primary, cultured, splenocytes, and, 'HaCaT', 'cells,', and, 'TMA-induced', 'GATA3', mRNA, expression, ex, vivo])]). relacion([sujeto(['AcRE', also]), verbo([suppressed]), complemento(['TMA-mediated', 'CCL11', and, 'IL-4-induced', 'CCL26', mRNA, expression, and, infiltration, of, 'CCR3', positive, cells])]). relacion([sujeto(['Taken', 'together,', these, results]), verbo([suggest]), complemento([that, 'AcRE', has, potential, for, development, as, an, agent, to, prevent, and, treat, allergic, contact, dermatitis])]). relacion([sujeto(['Previous', studies]), verbo([have]), complemento([documented, a, higher, amount, and, depth, of, myometrial, infiltration, by, the, implantation, site, intermediate, trophoblast, compared, with, controls])]). relacion([sujeto(['In', 'addition,', we]), verbo([have]), complemento([anecdotally, observed, chorionic, villi, in, myometrial, vascular, spaces, in, specimens, with, placenta, creta])]). relacion([sujeto(['This']), verbo([finding]), complemento([was, more, common, in, the, percreta, '(', 87.5, '%', ')', and, increta, '(', 84, '%', ')', than, in, the, accreta, '(', 27.2, '%', ',', 'P=0'])]). relacion([sujeto(['For', the, first, 'time,', we, document, the]), verbo([finding]), complemento([of, chorionic, villi, intrusion, into, myometrial, vascular, 'spaces,', which, is, highly, specific, of, placenta, creta])]). relacion([sujeto(['We', hypothesize, that, placental, invasion, in, placenta, creta, is, 'due,', at, least, 'partially,', to, transformation, of, 'low-resistance', myometrial, vessels]), verbo([leading]), complemento([to, subsequent, protrusion, of, villi, into, their, 'lumens,', in, the, context, of, absent, decidua])]). relacion([sujeto(['High', mobility, group, box, 1, '(', 'HMGB1)', is, an, inflammatory, mediator]), verbo([involved]), complemento([into, the, advanced, stage, of, systemic, inflammatory, response, syndrome, '(', 'SIRS),', and, is, 'over-expressed', in, bacterial, sepsis, and, hemorrhagic, shock])]). relacion([sujeto(['Recently,', it]), verbo([has]), complemento([been, found, that, the, 'HMGB1', was, abnormally, expressed, in, induced, sputum, and, plasma, of, asthmatic, patients])]). relacion([sujeto(['Therefore,', we, aim, to, investigate, the, role, 'HMGB1', in]), verbo([regulating]), complemento([airway, inflammation, of, acute, allergic, asthma, and, its, possible, mechanism, in, this, study])]). relacion([sujeto(['Moreover,', the, 'HMGB1', group, was, showed, an]), verbo([increased]), complemento([mucus, secretion, and, infiltration, of, eosinophils, and, neutrophils, in, the, airway, of, asthma, 'mice,', and, a, decrease, of, pulmonary, 'function,', compared, to, control, group, '(', 'P<0'])]). relacion([sujeto(['Meanwhile,', exogenous, 'HMGB1', could]), verbo([increase]), complemento([the, levels, of, 'IL-4,', 'IL-5,', 'IL-6,', 'IL-8', and, 'IL-17,', whereas, could, reduce, the, 'IFN-γ', in, the, 'BALF', and, lung, tissue, '(', 'P<0'])]). relacion([sujeto(['Exogenous', 'HMGB1', could]), verbo([enhance]), complemento(['GATA3', expression, of, 'Th2', cells, and, attenuate, the, 'T-bet', expression, of, 'Th1', cells, '(', 'P<0'])]). relacion([sujeto([5, ',', 'respectively),', which, could, be, abrogated, after]), verbo([inhibiting]), complemento(['HMGB1'])]). relacion([sujeto(['HMGB1', could, aggravate, eosinophilic, inflammation, in, the, airway, of, acute, allergic, asthma, through]), verbo([inducing]), complemento([a, dominance, of, 'Th2-type', response, and, promoting, the, neutrophilic, inflammation])]). relacion([sujeto(['These', findings]), verbo([provide]), complemento([a, new, insight, into, disease, pathogenesis, and, potential, therapeutic, approaches])]). relacion([sujeto([our, aim, was, to, evaluate, whether, somatic, mutations, in, five, genes, were]), verbo([associated]), complemento([with, an, early, age, at, presentation, of, breast, cancer, '(', 'BC)', or, serous, ovarian, cancer, '(', 'SOC)'])]). relacion([sujeto(['In', 'BC,', 'PIK3CA', wild, type, tumor, was]), verbo([associated]), complemento([with, early, 'onset,', not, confirmed, in, binary, regression, with, estrogen, receptor, '(', 'ER)', status])]). relacion([sujeto(['In', 'HER2-negative', 'tumors,', there, was]), verbo([increased]), complemento([frequency, of, 'PIK3CA', somatic, mutation, in, older, age, 'groups;', in, 'ER-positive', 'tumors,', there, was, a, trend, towards, an, increased, frequency, of, 'PIK3CA', somatic, mutation, in, older, age, groups])]). relacion([sujeto([frequency, of, somatic, mutations, in, specific, genes, was, not]), verbo([associated]), complemento([with, 'early-onset', breast, cancer])]). relacion([sujeto(['We']), verbo([report]), complemento([the, case, of, a, metastatic, lymph, node, collision, of, an, urothelial, carcinoma, and, a, prostatic, adenocarcinoma])]). relacion([sujeto(['He', was, followed, since, 2004, for, prostatic, adenocarcinoma, and, treated, with, radical, prostatectomy, then, radiation, therapy, 4, years, later, due, to, a, new]), verbo([increase]), complemento([of, 'PSA'])]). relacion([sujeto(['Metastatic', collision, of, urothelial, carcinoma, and, prostatic, adenocarcinoma]), verbo([has]), complemento([been, reported, in, 4, cases, only])]). relacion([sujeto(['The', transcription, factor, 'GATA-3', is, indispensable, for, the, development, of, all, innate, lymphoid, cells, '(', 'ILCs)', that]), verbo([express]), complemento([the, interleukin, 7, receptor, 'α-chain', '(', 'IL-7Rα)'])]). relacion([sujeto(['However,', the, function, of, low, 'GATA-3', expression, in, committed, group, 3, 'ILCs', '(', 'ILC3', 'cells)']), verbo([has]), complemento([not, been, identified])]). relacion([sujeto(['We']), verbo([found]), complemento([that, 'GATA-3', regulated, the, homeostasis, of, 'ILC3', cells, by, controlling, 'IL-7Rα', expression])]). relacion([sujeto(['In', 'addition,', 'GATA-3', served, a, critical, function, in, the, development, of, the, 'NKp46(+)', 'ILC3', subset, by]), verbo([regulating]), complemento([the, balance, between, the, transcription, factors, 'T-bet', and, 'RORγt'])]). relacion([sujeto(['Among', 'NKp46(+)', 'ILC3', 'cells,', although, 'GATA-3', positively]), verbo([regulated]), complemento([genes, specific, to, the, 'NKp46(+)', 'ILC3', 'subset,', it, negatively, regulated, genes, specific, to, lymphoid, 'tissue-inducer', '(', 'LTi)', or, 'LTi-like', 'ILC3', cells])]). relacion([sujeto(['Furthermore,', 'GATA-3', was]), verbo([required]), complemento([for, 'IL-22', production, in, both, 'ILC3', subsets])]). relacion([sujeto(['Initial', investigations]), verbo([reported]), complemento(['GATA3', to, be, a, sensitive, and, relatively, specific, marker, for, mammary, and, urothelial, carcinomas])]). relacion([sujeto(['Recently,', 'GATA3', expression]), verbo([has]), complemento([been, described, in, several, other, epithelial, tumors])]). relacion([sujeto(['However,', there]), verbo([has]), complemento([been, only, limited, investigation, of, 'GATA3', expression, in, cutaneous, epithelial, tumors])]). relacion([sujeto(['GATA3', was, consistently, and, usually, strongly]), verbo([expressed]), complemento([in, clear, cell, 'acanthoma,', 'trichofolliculoma,', 'trichoepithelioma,', 'trichilemmoma,', sebaceous, 'adenoma,', 'sebaceoma,', apocrine, 'hidrocystoma,', apocrine, tubular, papillary, 'adenoma,', hidradenoma, 'papilliferum,', and, syringocystadenoma, papilliferum])]). relacion([sujeto(['Our', findings, demonstrate, that, 'GATA3', is]), verbo([expressed]), complemento([in, a, wide, variety, of, benign, and, malignant, cutaneous, epithelial, neoplasms])]). relacion([sujeto(['In', addition, to, carcinomas, of, breast, and, urothelial, origin, and, other, more, recently, described, 'GATA3-positive', 'tumors,', the, differential, diagnosis, of, a, metastatic, tumor, of, unknown, primary, origin, that]), verbo([expresses]), complemento(['GATA3', should, also, include, a, carcinoma, of, cutaneous, epithelial, origin])]). relacion([sujeto(['We', showed, a, reduction, of, 'GATA3', and, 'RORc', 'mRNA,', low, 'Treg-related', cytokines, and, elevated, 'Th2', cytokine, levels, in, eosinophilic, chronic, 'rhinosinusitis,', whereas, we, demonstrated, the, upregulation, of, 'Treg', cells, and]), verbo([increases]), complemento([of, 'Th1', and, 'Th17', cytokines, in, 'non-eosinophilic', chronic, rhinosinusitis, in, the, 'Japanese', population])]). relacion([sujeto(['The', different, mRNA, expression, profiles, of, 'Treg', and, 'Th1/Th2/Th17', signature, transcription, factors, and, cytokines, between, eosinophilic, chronic, rhinosinusitis, and, 'non-eosinophilic', chronic, rhinosinusitis]), verbo([suggests]), complemento([heterogeneity, in, the, pathogenesis, of, chronic, rhinosinusitis, with, nasal, polyps])]). relacion([sujeto(['Both', cytokines]), verbo([induce]), complemento(['fate-decisive', transcription, factors, such, as, 'GATA3', and, 'TBX21', that, antagonize, the, polarized, development, of, opposite, phenotypes, by, direct, regulation, of, each, 'other\'s', expression, along, with, many, other, target, genes])]). relacion([sujeto(['Although', it, is, well, established, that, mesenchymal, cells, directly]), verbo([respond]), complemento([to, 'Th1', and, 'Th2', 'cytokines,', the, nature, of, antagonistic, differentiation, programs, in, airway, epithelial, cells, is, only, partially, understood])]). relacion([sujeto(['The', study, uncovers, an, antagonistic, regulation, pattern, of, 'IL-4', and, 'IFN-γ', in, 'NHBEs,']), verbo([translating]), complemento([the, 'Th1/Th2', antagonism, directly, in, epithelial, gene, regulation])]). relacion([sujeto(['The', extent, to, which, heritable, genetic, variants, can, affect, tumor, development]), verbo([has]), complemento([yet, to, be, fully, elucidated])]). relacion([sujeto(['Tumor', selection, of, single, nucleotide, polymorphism, '(', 'SNP)', risk, 'alleles,', a, phenomenon, called, preferential, allelic, imbalance, '(', 'PAI),']), verbo([has]), complemento([been, demonstrated, in, some, cancer, types])]). relacion([sujeto(['We', developed, a, novel, application, of, digital, 'PCR', termed, 'Somatic', 'Mutation', 'Allelic', 'Ratio', 'Test', using, 'Droplet', 'Digital', 'PCR', '(', 'SMART-ddPCR)', for, accurate, assessment, of, tumor, 'PAI,', and]), verbo([have]), complemento([applied, this, method, to, test, the, hypothesis, that, heritable, 'SNPs', associated, with, childhood, acute, lymphoblastic, leukemia, '(', 'ALL)', may, demonstrate, tumor, 'PAI'])]). relacion([sujeto(['We', did, not]), verbo([find]), complemento([significant, tumor, 'PAI', at, these, 'loci,', though, 'CDKN2A', and, 'IKZF1', 'SNPs', showed, a, trend, towards, preferential, selection, of, the, risk, allele, '(', p, =, 0.17, and, p, =, 0.23, ',', 'respectively)'])]). relacion([sujeto(['Using', a, genomic, copy, number, control, ddPCR, 'assay,', we, investigated, somatic, copy, number, alterations, '(', 'SCNA)', underlying, 'AI', at, 'CDKN2A', and, 'IKZF1,']), verbo([revealed]), complemento([a, complex, range, of, alterations, including, homozygous, and, hemizygous, deletions, and, 'copy-neutral', loss, of, 'heterozygosity,', with, varying, degrees, of, clonality])]). relacion([sujeto(['Furthermore,', analysis, of, publicly, available, data, from, 'The', 'Cancer', 'Genome', 'Atlas', identified, 16, recurrent, 'SCNA', loci, that, contain, heritable, cancer, risk, 'SNPs']), verbo([associated]), complemento([with, a, matching, tumor, 'type,', and, which, represent, candidate, 'PAI', regions, warranting, further, investigation])]). relacion([sujeto(['The', 'Th2', pathway, starts, with, the]), verbo([binding]), complemento([of, 'IL-4', to, the, 'IL-4', receptor, followed, by, the, phosphorylation, of, signal, transducer, and, activator, of, transcription, 6, and, the, activation, of, 'GATA3'])]). relacion([sujeto(['ILC2s']), verbo([respond]), complemento([to, 'IL-25,', 'IL-33,', thymic, stromal, 'lymphopoietin,', and, leukotrienes, by, producing, 'IL-4,', 'IL-5,', and, 'IL-13'])]). relacion([sujeto(['In', addition, to, all, this, 'inflammatory-cell-driven', 'asthma,']), verbo([increasing]), complemento([evidence, has, emerged, relating, to, smooth, muscle, cell, 'activation,', the, endothelial, and, epithelial, barrier, 'functions,', and, improvements, in, the, barrier, function])]). relacion([sujeto(['Epithelial', cells, and, endothelial, cells, lose, barrier, function, in, the, context, of, allergic, airway, 'inflammation,', and, this, could, be, at, least, partially, remedied, by]), verbo([increasing]), complemento([the, intracellular, cyclic, adenosine, monophosphate, levels, through, phosphodiesterase, inhibition])]). relacion([sujeto(['Early', regulators, of, disease, may]), verbo([increase]), complemento([understanding, of, disease, mechanisms, and, serve, as, markers, for, presymptomatic, diagnosis, and, treatment])]). relacion([sujeto(['We', hypothesized, that, early, regulators, of, 'T', 'cell-associated', diseases, could, be]), verbo([found]), complemento([by, identifying, upstream, transcription, factors, '(', 'TFs)', in, 'T', cell, differentiation, and, by, prioritizing, hub, 'TFs', that, were, enriched, for, 'disease-associated', polymorphisms])]). relacion([sujeto(['A', gene, regulatory, network, '(', 'GRN)', was, constructed, by, time, series, profiling, of, the, transcriptomes, and, methylomes, of, human, 'CD4(+)', 'T', cells, during, in, vitro, differentiation, into, four, helper, 'T', cell, 'lineages,', in, combination, with, 'sequence-based', 'TF']), verbo([binding]), complemento([predictions])]). relacion([sujeto(['Differential', mRNA, expression, of, the, 'TFs', and, their]), verbo([targets]), complemento([in, 'T', 'cell-associated', diseases, supports, their, clinical, relevance])]). relacion([sujeto(['Strikingly,', the, 'TFs', were, differentially]), verbo([expressed]), complemento([during, asymptomatic, stages, of, both, 'diseases,', whereas, their, targets, showed, altered, expression, during, symptomatic, stages])]). relacion([sujeto(['A', previous, 'genome-wide', association, study, identified, common, polymorphisms, at, the, 'LMO1', gene, locus, that, are, highly]), verbo([associated]), complemento([with, neuroblastoma, susceptibility, and, oncogenic, addiction, to, 'LMO1', in, the, tumour, cells])]). relacion([sujeto(['Here', we, investigate, the, causal, 'DNA', variant, at, this, locus, and, the, mechanism, by, which, it]), verbo([leads]), complemento([to, neuroblastoma, tumorigenesis])]). relacion([sujeto(['We', first, imputed, all, possible, genotypes, across, the, 'LMO1', locus, and, then, mapped, highly]), verbo([associated]), complemento([single, nucleotide, polymorphism, '(', 'SNPs)', to, areas, of, chromatin, 'accessibility,', evolutionary, conservation, and, transcription, factor, binding, sites])]). relacion([sujeto(['We', show, that, 'SNP', rs2168101, 'G>T', is, the, most, highly]), verbo([associated]), complemento([variant, '(', combined, 'P', =, 7.47, ×, 10, '(', -, 29, ')', ',', odds, ratio, 0.65, ',', 95, '%', confidence, interval, 0.6, -, 0.7, ')', ',', and, resides, in, a, 'super-enhancer', defined, by, extensive, acetylation, of, histone, 'H3', lysine, 27, within, the, first, intron, of, 'LMO1'])]). relacion([sujeto(['The', ancestral, 'G', allele, that, is]), verbo([associated]), complemento([with, tumour, formation, resides, in, a, conserved, 'GATA', transcription, factor, binding, motif])]). relacion([sujeto(['We', show, that, the, newly, evolved, protective, 'TATA', allele, is]), verbo([associated]), complemento([with, decreased, total, 'LMO1', expression, '(', 'P', =, 0.028, ')', in, neuroblastoma, primary, 'tumours,', and, ablates, 'GATA3', binding, '(', 'P', &, 'lt;', 0.0001, ')'])]). relacion([sujeto(['These', findings, indicate, that, a, recently, evolved, polymorphism, within, a, 'super-enhancer', element, in, the, first, intron, of, 'LMO1', influences, neuroblastoma, susceptibility, through, differential, 'GATA', transcription, factor]), verbo([binding]), complemento([and, direct, modulation, of, 'LMO1', expression, in, 'cis,', and, this, leads, to, an, oncogenic, dependency, in, tumour, cells])]). relacion([sujeto(['Studies']), verbo([have]), complemento([examined, gene, expression, changes, in, 'Sézary', syndrome, '(', 'SS),', but, disease, pathogenesis, remains, largely, 'unknown,', and, diagnosis, and, treatment, are, difficult])]). relacion([sujeto(['TOX', is, a, transcription, factor]), verbo([involved]), complemento([in, 'CD4+', 'T-cell', development, with, downstream, effects, on, 'RUNX3,', a, known, tumor, suppressor, gene])]). relacion([sujeto(['We', sought, to, identify, genes]), verbo([involved]), complemento([in, 'SS', disease, pathogenesis, with, the, potential, to, enable, diagnosis, and, treatment])]). relacion([sujeto(['We', utilized, previously]), verbo([reported]), complemento([transcriptome, sequencing, data, to, construct, a, list, of, candidate, 'genes,', which, was, narrowed, using, pathway, analysis])]). relacion([sujeto(['Using', siRNA, to]), verbo([suppress]), complemento(['TOX,', we, demonstrated, that, 'TOX', knockdown, rescues, 'RUNX3', expression, and, reduces, cell, viability])]). relacion([sujeto(['We', evaluated, 'TOX', protein, expression, in, 'paraffin-embedded', skin, biopsies, with, 'immunohistochemistry,', showing]), verbo([nuclear]), complemento([staining, of, 'CTCL', 'infiltrates,', suggesting, it, is, a, candidate, diagnostic, biomarker])]). relacion([sujeto(['Further', studies, validating, our, findings, and, evaluating, the, 'TOX-RUNX3', pathway, and, the, role, of, 'TOX', as, a, disease, marker, and, therapeutic]), verbo([target]), complemento([are, warranted])]). relacion([sujeto(['Allergic', airway, inflammation, '(', 'AAI)', in, response, to, environmental, antigens, is, an]), verbo([increasing]), complemento([medical, 'problem,', especially, in, the, 'Western', world])]). relacion([sujeto(['Th', cells, essentially]), verbo([required]), complemento(['IL-33', to, become, either, 'GATA3(+)', or, 'GATA3(+)/Foxp3(+)', hybrids])]). relacion([sujeto(['Absence', of, adaptive, immunity, in, 'rag2(-/-)', mice, resulted, in, attenuated, 'AAI,']), verbo([revealed]), complemento([the, need, for, 'Th2', cells, for, full, 'AAI', development])]). relacion([sujeto(['Taken', 'together,', in, pulmonary, cryptococcosis, 'ILC2', and, 'GATA3(+)', 'Th2', cells, produce, early, 'IL-13', largely, 'IL-33R-dependent,', thereby]), verbo([promoting]), complemento([goblet, cell, 'metaplasia,', pulmonary, 'eosinophilia,', and, alternative, activation, of, alveolar, macrophages])]). relacion([sujeto(['Primary', mucinous, adenocarcinoma, of, the, female, urethra, is, very, rare, and, may]), verbo([lead]), complemento([to, both, diagnostic, and, therapeutic, challenges])]). relacion([sujeto(['Although', primary, mucinous, adenocarcinoma, of, the, prostate, and, prostatic, urethra]), verbo([has]), complemento([been, well, characterized, in, 'men,', this, is, the, largest, clinicopathologic, study, to, date, of, primary, mucinous, adenocarcinoma, of, the, female, urethra])]). relacion([sujeto(['Interleukin', 12, receptor, β, chain, '(', 'IL12RB2)', is, a, crucial, regulatory, factor]), verbo([involved]), complemento([in, 'cell-mediated', immune, 'responses,', and, genetic, variants, of, the, gene, encoding, 'IL12RB2', are, associated, with, susceptibility, to, various, 'immune-related', diseases])]). relacion([sujeto(['In', the, present, 'study,', we, identified, transcription, factors]), verbo([associated]), complemento([with, the, 'haplotype-specific', transcriptional, activity, of, 'IL12RB2', in, 'T', cells, and, 'NK', cells])]). relacion([sujeto(['The', -, 1023, 'G', polymorphism, was]), verbo([found]), complemento([to, create, a, consensus, binding, site, for, the, transcription, factor, activating, protein, '(', 'AP)-1,', and, 'enzyme-linked', immunosorbent, assay, '(', 'ELISA)-based', binding, assays, showed, that, these, 'SNPs', enhanced, 'AP-1', binding, to, this, region])]). relacion([sujeto(['These', results]), verbo([suggested]), complemento([that, the, -, 1035, /, -, 1023, polymorphisms, created, differential, binding, affinities, for, 'JunB', that, could, lead, to, differential, 'IL12RB2', expression])]). relacion([sujeto(['Moreover,', the, -, 1035, 'G', and, -, 1035, 'A', alleles, formed]), verbo([binding]), complemento([sites, for, 'GATA-3', and, myocyte, enhancer, 'factor-2', '(', 'MEF-2),', respectively])]). relacion([sujeto(['Our', data, indicated, that, in, addition, to, 'JunB,', the, 'SNP', at, -, 1035, /, -, 1023, influenced, 'GATA-3', and, 'MEF-2']), verbo([binding]), complemento(['affinity,', potentially, altering, 'IL12RB2', transcriptional, activity])]). relacion([sujeto(['Alopecia', areata, represents, an, autoimmune, pathological, process, driven, primarily, by, cellular, aberrations, contained, within, the, immune, 'system,', which]), verbo([activates]), complemento([various, humoral, and, cellular, elements, of, the, immune, response])]). relacion([sujeto(['Notably,', positive, correlation, '(', 'P', &, 'lt;', 0.05, ')', was]), verbo([found]), complemento([between, 'IFN-γ', and, 'T-bet', levels, in, patients, and, controls])]). relacion([sujeto(['We']), verbo([have]), complemento([identified, a, 'Forkhead', family, transcription, 'factor,', 'Foxi3,', that, is, expressed, in, the, 'pre-placodal', domain, and, 'down-regulated', when, the, otic, placode, is, induced])]). relacion([sujeto(['Some', preplacodal, genes, downstream, of, 'Foxi3-Gata3,', 'Six1', and, 'Eya1-are', not]), verbo([expressed]), complemento([in, the, ectoderm, of, 'Foxi3', mutant, 'mice,', and, the, ectoderm, exhibits, signs, of, increased, apoptosis])]). relacion([sujeto(['Our', data]), verbo([suggest]), complemento([that, 'Foxi3', is, necessary, to, prime, 'pre-placodal', ectoderm, for, the, correct, interpretation, of, inductive, signals, for, the, otic, and, epibranchial, placodes])]). relacion([sujeto(['We', sought, to, define, markers, differentially]), verbo([expressed]), complemento([in, human, 'monocyte-derived', 'DCs', differentiated, toward, a, proallergic, '(', 'DCs', driving, the, differentiation, of, 'TH2', cells, '[', 'DC2s])', phenotype, and, investigate, whether, changes, in, such, markers, in, the, blood, correlate, with, 'AIT', efficacy])]). relacion([sujeto(['Markers', differentially]), verbo([regulated]), complemento([in, 'DC2s', and, 'DCreg', cells, were, assessed, by, means, of, quantitative, 'PCR', in, 'PBMCs', from, 80, patients, with, grass, pollen, allergy, before, and, after, 2, or, 4, &, 'nbsp;months', of, sublingual, 'AIT', in, parallel, with, rhinoconjunctivitis, symptom, scores])]). relacion([sujeto(['A', combination, of, 5, markers, predominantly]), verbo([expressed]), complemento([by, blood, 'DCs', '(', 'ie,', 'C1Q', and, 'CD141)', or, shared, with, lymphoid, cells, '(', 'ie,', 'FcγRIIIA,', 'GATA3,', and, 'RIPK4)', reflecting, changes, in, the, balance, of, 'regulatory/proallergic', responses, in, peripheral, blood, can, be, used, as, early, as, after, 2, &, 'nbsp;months', to, monitor, the, early, onset, of, 'AIT', efficacy])]). relacion([sujeto(['To', investigate, the, level, of, 'interleukin-19', '(', 'IL-19)', in, the, peripheral, blood, of, the, patients, with, allergic, rhinitis, '(', 'AR)', and]), verbo([reveal]), complemento([the, possible, role, of, 'IL-19', in, the, development, of, disease])]). relacion([sujeto(['Moreover,', 'PBMCs', from, the, 'AR', group, were]), verbo([stimulated]), complemento([by, recombinant, 'IL-19', or, 'PBS,', and, then, the, frequency, of, 'Th2', 'cells,', levels, of, 'GATA', binding, 'protein-3', '(', 'GATA-3)', mRNA, and, 'IL-4', protein, in, 'PBMCs', were, detected, by, flow, 'cytometry,', 'qRT-PCR', and, 'ELISA,', respectively])]). relacion([sujeto(['The', level, of, 'IL-19', in, the, peripheral, blood, of, 'AR', patients]), verbo([increased]), complemento([and, was, related, with, the, clinical, severity, of, 'AR'])]). relacion([sujeto(['Numerous', studies]), verbo([have]), complemento([focused, on, the, molecular, regulation, of, perforin, '(', 'PFP)', and, granzyme, 'B', '(', 'GZMB)', expression, by, activated, cytotoxic, 'T', lymphocytes, '(', 'CTLs),', but, little, is, known, about, the, molecular, factors, that, underpin, granzyme, 'A', '(', 'GZMA)', expression])]). relacion([sujeto(['In', vitro, activation, of, naïve, 'CD8(+)', 'T', 'cells,', in, the, presence, of, 'IL-4,']), verbo([enhanced]), complemento(['STAT6-dependent', 'GZMA', expression, and, was, associated, with, 'GATA3', binding, and, enrichment, of, transcriptionally, permissive, histone, posttranslational, modifications, '(', 'PTMs)', across, the, 'Gzma', gene, locus])]). relacion([sujeto(['While', 'GZMA', expression, by, effector, influenza, 'A', virus, specific, 'CTLs', was, also]), verbo([associated]), complemento([with, a, similar, permissive, epigenetic, 'signature,', memory, 'CTL', lacked, enrichment, of, permissive, histone, 'PTMs', at, the, 'Gzma', 'locus,', although, this, was, restored, within, recalled, secondary, effector, 'CTLs'])]). relacion([sujeto(['Importantly,', 'GZMA', expression, 'by virus-specific', 'CTLs was']), verbo([associated]), complemento([with, 'GATA3', binding, at, the, 'Gzma', 'locus,', and, independent, of, 'STAT6-mediated', signaling])]). relacion([sujeto(['This']), verbo([suggests]), complemento([regulation, of, 'GZMA', expression, is, underpinned, by, 'differentiation-dependent regulation', of, chromatin, composition, at, the, 'Gzma', locus, and, 'that,', given, 'GATA3', is, key, for, 'CTL', differentiation, in, response, to, 'infection,', 'GATA3', expression, is, regulated, by, a, 'distinct,', 'IL-4', 'independent,', signaling, pathway])]). relacion([sujeto(['Overall,', this, study]), verbo([provides]), complemento([insights, into, the, molecular, mechanisms, that, control, transcription, of, 'Gzma', during, 'virus-induced', 'CD8(+)', 'T-cell', differentiation])]). relacion([sujeto(['Mesonephric', adenocarcinoma, is, a, rare, tumor, type, that, is, usually]), verbo([found]), complemento([in, areas, where, the, 'Wolffian', duct, was, present, during, the, fetal, period])]). relacion([sujeto(['We']), verbo([report]), complemento([a, case, of, mesonephric, adenocarcinoma, of, the, uterine, corpus, in, a, 66, -, 'year-old', woman, who, presented, with, vaginal, bleeding])]). relacion([sujeto(['Mesonephric', neoplasms]), verbo([reveal]), complemento([relatively, 'low-grade', nuclear, 'feature,', characteristic, immunoprofiles, '(', immunonegative, for, 'ER', and, 'PR,', and, immunopositive, for, 'CD10,', 'PAX2,', 'PAX8,', and, 'GATA3),', and, unique, tumor, location, '(', 'myometrium),', whereas, 'Müllerian', neoplasms, such, as, endometrial, adenocarcinoma, show, various, 'morphology,', immunopositivity, for, 'ER', and, 'PR,', and, primarily, endometrial, location])]). relacion([sujeto(['Molecular', heterogeneity, in, human, breast, cancer]), verbo([has]), complemento([challenged, 'diagnosis,', 'prognosis,', and, clinical, treatment])]). relacion([sujeto(['It', is, well, known, that, molecular, subtypes, of, breast, tumors, are]), verbo([associated]), complemento([with, significant, differences, in, prognosis, and, survival])]). relacion([sujeto(['Assuming', that, the, differences, are, attributed, to, 'subtype-specific', 'pathways,', we, then, suspect, that, there, might, be, gene, regulatory, mechanisms, that]), verbo([modulate]), complemento([the, behavior, of, the, pathways, and, their, interactions])]). relacion([sujeto(['Using', existing, data, from, three, large, cohorts, of, human, breast, cancer, 'populations,', we]), verbo([have]), complemento([identified, an, ensemble, of, 16, master, regulator, genes, '(', or, 'MR16)', that, can, discriminate, breast, tumor, samples, into, four, major, subtypes])]). relacion([sujeto(['Evidence', from, gene, expression, across, the, three, cohorts]), verbo([has]), complemento([consistently, indicated, that, the, 'MR16', can, be, divided, into, two, groups, that, demonstrate, 'subtype-specific', gene, expression, patterns])]). relacion([sujeto(['For', 'example,', group, 1, 'MRs,', including, 'ESR1,', 'FOXA1,', and, 'GATA3,', are, overexpressed, in, luminal, 'A', and, luminal, 'B', 'subtypes,', but, lowly]), verbo([expressed]), complemento([in, 'HER2-enriched', and, 'basal-like', subtypes])]). relacion([sujeto(['Furthermore,', evidence, from, mutual, information, modeling]), verbo([has]), complemento([congruently, indicated, that, the, two, groups, of, 'MRs', either, 'up-', or, 'down-regulate', cancer, 'driver-related', genes, in, opposite, directions])]). relacion([sujeto(['Furthermore,', integration, of, somatic, mutations, with, pathway, changes]), verbo([leads]), complemento([to, identification, of, canonical, genomic, alternations, in, a, 'subtype-specific', fashion])]). relacion([sujeto(['Taken', 'together,', these, studies]), verbo([have]), complemento([implicated, a, gene, regulatory, program, for, breast, tumor, progression])]). relacion([sujeto(['GATA3', is, a, transcription, factor]), verbo([regulating]), complemento([luminal, cell, differentiation, in, the, mammary, glands, and, has, been, implicated, in, the, luminal, types, of, breast, carcinoma])]). relacion([sujeto(['Moreover,', high, 'GATA3', expression, was, significantly]), verbo([associated]), complemento([with, favorable, 'relapse-free', survival, and, overall, survival])]). relacion([sujeto(['These', findings]), verbo([suggest]), complemento([that, 'GATA3', may, not, act, solely, as, a, luminal, differentiation, 'marker,', and, further, uncovering, the, molecular, pathways, by, which, 'GATA3', regulates, the, downstream, targets, will, be, crucial, to, our, understanding, of, breast, cancer, dissemination])]). relacion([sujeto(['To']), verbo([report]), complemento([a, series, of, uterine, corpus, '(', n, =, 7, ')', and, ovarian, '(', n, =, 5, ')', neoplasms, which, we, believe, probably, represent, mesonephric, adenocarcinomas, based, on, their, characteristic, morphology, and, immunophenotype])]). relacion([sujeto(['The']), verbo([nuclear]), complemento([features, were, characteristic, with, atypical, angulated, clear, vesicular, nuclei, which, often, exhibited, overlapping])]). relacion([sujeto(['All', the, tumours, were, '\'', 'flat\'', negative, with, oestrogen, receptor, and, progesterone, receptor, and, all, except, one, exhibited]), verbo([nuclear]), complemento([staining, with, thyroid, transcription, factor, 1, '(', 'TTF1),', which, was, often, diffuse])]). relacion([sujeto(['CD10,', calretinin, and, 'GATA']), verbo([binding]), complemento([protein, 3, '(', 'GATA3)', were, positive, in, a, variable, proportion, of, the, neoplasms])]). relacion([sujeto(['We', believe, these, neoplasms, to, represent, mesonephric, adenocarcinomas, which]), verbo([have]), complemento([only, rarely, been, reported, to, arise, in, the, uterine, corpus, and, never, in, the, ovary])]). relacion([sujeto(['We']), verbo([have]), complemento([recently, demonstrated, that, 'Caerulomycin', 'A', induces, regulatory, 'T', cells, differentiation, by, suppressing, 'Th1', cells, activity])]). relacion([sujeto(['The', role, of, regulatory, 'T', cells, is, well, established, in]), verbo([suppressing]), complemento([the, function, of, 'Th2', cells])]). relacion([sujeto(['Consequently,', in, the, present, 'study,', we, monitored, the, influence, of, 'Caerulomycin', 'A', in]), verbo([inhibiting]), complemento([the, activity, of, 'Th2', cells, and, its, impact, in, recuperating, asthma, symptoms])]). relacion([sujeto(['Interestingly,', we, observed, that, 'Caerulomycin', 'A', significantly]), verbo([suppressed]), complemento([the, differentiation, of, 'Th2', 'cells,', as, evidenced, by, downregulation, in, the, 'GATA-3', expression])]). relacion([sujeto(['The', production, of, 'IFNγ', by, 'Th1', or, 'Tc1', cells, was, sharply]), verbo([decreased]), complemento([and, was, accompanied, by, reduced, 'T-bet', 'mRNA,', even, when, total, 'T-cell', numbers, had, 'recovered;', the, frequencies, of, 'Th17', and, 'Treg', cells, and, their, specific, transcription, factors, '(', 'RORγt', and, 'Foxp3,', 'respectively)', were, obviously, increased])]). relacion([sujeto(['Pretreatment', with, cinnamon, in, irradiated, mice, accelerated, the, generation, of, 'Th1', and, reduced, the, differentiation, of, 'Treg', cells, by]), verbo([activating]), complemento(['T-bet', and, limiting, transcriptions, of, 'Foxp3'])]). relacion([sujeto(['Improvement', resulting, from, cinnamon, pretreatment, on, the, efficient, 'T-cell', recovery, profile, from, 'SLTBI']), verbo([promoted]), complemento([antitumor, immunity, in, the, lung, melanoma, model])]). relacion([sujeto(['Cinnamon', effectively, improved, the, imbalance, of, 'T-cell', subsets, by]), verbo([promoting]), complemento([the, proliferation, of, 'Th1', and, by, suppressing, expansions, of, 'Th17', and, 'Tregs'])]). relacion([sujeto(['In', 'Hodgkin', lymphoma, '(', 'HL)', we, recently, identified, deregulated, expression, of, homeobox, genes, 'MSX1', and, 'OTX2', which, are, physiologically]), verbo([involved]), complemento([in, development, of, the, embryonal, neural, plate, border, region])]). relacion([sujeto(['Here,', we, examined, in, 'HL', homeobox, gene, 'SIX1', an, additional, regulator, of, this, embryonal, region]), verbo([mediating]), complemento([differentiation, of, placodal, precursors])]). relacion([sujeto(['SIX1', was, aberrantly]), verbo([activated]), complemento([in, 12, '%', of, 'HL', patient, samples, in, 'silico,', indicating, a, pathological, role, in, a, subset, of, this, 'B-cell', malignancy])]). relacion([sujeto(['In', 'addition,', 'SIX1', expression, was, detected, in, 'HL', cell, lines, which, were, used, as, models, to]), verbo([reveal]), complemento([upstream, factors, and, target, genes, of, this, basic, developmental, regulator])]). relacion([sujeto(['We', detected]), verbo([increased]), complemento([copy, numbers, of, the, 'SIX1', locus, at, chromosome, 14, q23, correlating, with, enhanced, expression, while, chromosomal, translocations, were, absent])]). relacion([sujeto(['Moreover,', comparative, expression, profiling, data, and, pertinent, gene, modulation, experiments, indicated, that, the, 'WNT-signalling', pathway, and, transcription, factor, 'MEF2C']), verbo([regulate]), complemento(['SIX1', expression])]). relacion([sujeto(['Genes', encoding, the, transcription, factors, 'GATA2,', 'GATA3,', 'MSX1', and, 'SPIB', -, all, basic, lymphoid, regulators, -, were, identified, as]), verbo([targets]), complemento([of, 'SIX1', in, 'HL'])]). relacion([sujeto(['In', 'addition,', cofactors, 'EYA1', and, 'TLE4,', 'respectively,', contrastingly]), verbo([mediated]), complemento([activation, and, suppression, of, 'SIX1', target, gene, expression])]). relacion([sujeto(['Thus,', the, protein, domain, interfaces, may, represent, therapeutic]), verbo([targets]), complemento([in, 'SIX1-positive', 'HL', subsets])]). relacion([sujeto(['Collectively,', our, data]), verbo([reveal]), complemento([a, gene, regulatory, network, with, 'SIX1', centrally, deregulating, lymphoid, differentiation, and, support, concordance, of, 'lymphopoiesis/lymphomagenesis', and, developmental, processes, in, the, neural, plate, border, region])]). relacion([sujeto(['Periodontitis', is, a, chronic, inflammatory, disease]), verbo([triggered]), complemento([by, the, host, immune, response])]). relacion([sujeto(['CCL25', plays, an, important, role, in, 'T-cell', 'development,', whereas, 'IL17C']), verbo([regulates]), complemento([innate, epithelial, immune, responses])]). relacion([sujeto(['The']), verbo([decrease]), complemento([in, 'CpG', methylation, is, presumably, accompanied, by, an, increase, in, gene, expression])]). relacion([sujeto(['This', could]), verbo([lead]), complemento([to, a, greater, availability, of, 'CCL25', and, interleukin, 17, 'C', and, support, periodontal, loss, of, attachment])]). relacion([sujeto(['Previously,', several, groups, including, ours]), verbo([have]), complemento([shown, that, young, age, at, diagnosis, is, associated, with, higher, prevalence, of, 'basal-like', tumors, and, aggressive, tumor, phenotypes])]). relacion([sujeto(['Eleven', mutations, were, independently]), verbo([associated]), complemento([with, age, at, 'diagnosis,', of, which, only, 'GATA3', was, associated, with, young, age, '(', 15.2, '%', versus, 8.2, '%', versus, 9, '%', ;, 'P', =, 0.003, ')'])]). relacion([sujeto(['Only', two, 'CNV', events, were, independently]), verbo([associated]), complemento([with, 'age,', with, more, chr18p, losses, in, older, patients, and, more, chr6q27, deletions, in, younger, ones])]). relacion([sujeto(['Younger', age, at, diagnosis, was]), verbo([associated]), complemento([with, higher, expression, of, gene, signatures, related, to, 'proliferation,', stem, cell, features, and, endocrine, resistance])]). relacion([sujeto(['Age', adds, a, layer, of, biological, complexity, beyond, breast, cancer, molecular, 'subtypes,', classic, pathological, and, clinical, 'variables,', worthy, of, further, consideration, in, future, drug, development, as, we, seek, to, refine, therapeutic, strategies, in, the]), verbo([era]), complemento([of, personalized, medicine])]). relacion([sujeto(['GATA']), verbo([binding]), complemento([protein, 3, '(', 'GATA3)', has, emerged, as, a, potentially, useful, immunohistochemical, adjunct, during, the, evaluation, of, metastatic, breast, carcinomas, in, cytology, specimens])]). relacion([sujeto(['This', study, evaluates, immunohistochemical, markers, for, the, differential, diagnosis, of, primary, bladder, adenocarcinoma, '(', 'BAC)', from, secondarily]), verbo([involving]), complemento([colorectal, adenocarcinoma, '(', 'CAC)'])]). relacion([sujeto(['Further', significant, difference, between, 'BAC', and, 'CAC', was]), verbo([found]), complemento([for, 'GATA3', and, nuclear, 'ß-catenin', staining])]). relacion([sujeto(['Differential', diagnosis, of, 'BAC', and, 'CAC', remains, 'difficult,', but, positive, staining, for, keratin, 7, in]), verbo([nuclear]), complemento(['ß-catenin-negative', tumours, argues, for, 'BAC'])]). relacion([sujeto(['The', development, of, the, 'DC', lineage, and, their, subsets]), verbo([requires]), complemento([an, orchestrated, regulation, of, their, transcriptional, program])]). relacion([sujeto(['Gata1,', a, transcription, factor]), verbo([expressed]), complemento([in, several, hematopoietic, cell, 'lineages,', has, been, recently, reported, to, be, required, for, mouse, 'DC', development, and, function])]). relacion([sujeto(['In', 'humans,', 'GATA1', is]), verbo([involved]), complemento([in, the, lineage, separation, between, 'monocyte-derived', 'DCs', and, 'Langerhans', cells, '(', 'LC)', and, loss, of, 'GATA1', results, in, differentiation, arrest, at, the, monocyte, stage])]). relacion([sujeto(['Gata1,', 'Gata2,', 'Gata3)', are, known, to]), verbo([regulate]), complemento([each, 'other\'s', expression, and, to, function, consecutively, throughout, lineage, commitment, '(', 'so-called', 'GATA', 'switch)'])]). relacion([sujeto(['In', 'humans,', mutations, in, 'GATA2', are, causative, of, 'MonoMAC', 'disease,', a, human, immunodeficiency, syndrome, characterized, by]), verbo([loss]), complemento([of, 'DCs,', 'monocytes,', 'B', and, 'NK', cells])]). relacion([sujeto(['In', this, 'study,', we]), verbo([have]), complemento([characterized, the, expression, of, hematopoietic, 'GATA', factors, in, murine, and, human, 'DCs', and, their, expression, dynamics, upon, 'TLR', stimulation])]). relacion([sujeto(['We']), verbo([found]), complemento([that, all, hematopoietic, 'GATA', factors, are, expressed, in, 'DCs,', but, identified, 'species-specific', differences, in, the, relative, expression, of, each, 'GATA', 'factor,', and, how, their, expression, fluctuates, upon, stimulation])]). relacion([sujeto(['Tumors', of, trophoblastic, derivation, other, than, choriocarcinoma, are, very, rare, in, the, testis, but]), verbo([have]), complemento([been, reported, on, occasion, in, association, with, other, germ, cell, tumors])]). relacion([sujeto(['Herein', we]), verbo([report]), complemento([our, experience, with, 8, cases, of, trophoblastic, tumors, of, testicular, origin, that, lacked, the, features, of, 'choriocarcinoma;', these, included, 4, 'ETTs,', 1, 'PSTT,', 1, unclassified, trophoblastic, tumor, '(', 'UTT),', 1, partially, regressed, choriocarcinoma, with, a, monophasic, 'morphology,', and, 1, hybrid, tumor, showing, a, mixture, of, adenocarcinoma, and, a, 'UTT'])]). relacion([sujeto(['Five', arose, de, novo, within, the, testis, '(', 2, 'ETTs,', 1, 'UTT,', 1, regressing, 'choriocarcinoma,', and, the, hybrid, 'tumor)', as, a, component, of, mixed, germ, cell, 'tumors,', and, 3, '(', 2, 'ETTs', and, 1, 'PSTT)', were]), verbo([found]), complemento([in, metastatic, sites, after, chemotherapy])]). relacion([sujeto(['The', hybrid, tumor, had, 'ETT-like', and, adenocarcinomatous, areas, that, coexpressed, inhibin, and, 'GATA3', but, were, negative, for, p63, and, 'HPL,']), verbo([leading]), complemento([to, classification, of, the, trophoblastic, component, as, 'UTT'])]). relacion([sujeto(['The', metastastic, cascade, is, a, complex, process, that, is]), verbo([regulated]), complemento([at, multiple, levels, in, prostate, cancer, '(', 'PCa)'])]). relacion([sujeto(['Recent', evidence]), verbo([suggests]), complemento([that, microRNAs, '(', 'miRNAs)', are, involved, in, 'PCa', metastasis, and, hold, great, promise, as, therapeutic, targets])]). relacion([sujeto(['In', this, 'study,', we]), verbo([found]), complemento([that, 'miR-573', expression, is, significantly, lower, in, metastatic, tissues, than, matched, primary, 'PCa'])]). relacion([sujeto(['Through', 'gain-', and, 'loss-of', function, 'experiments,', we, demonstrated, that, 'miR-573']), verbo([inhibits]), complemento(['PCa', cell, 'migration,', invasion, and, 'TGF-β1-induced', 'epithelial-mesenchymal', transition, '(', 'EMT)', in, vitro, and, lung, metastasis, in, vivo])]). relacion([sujeto(['Mechanistically,', miR573, directly]), verbo([targets]), complemento([the, fibroblast, growth, factor, receptor, 1, '(', 'FGFR1)', gene])]). relacion([sujeto(['Consequently,', 'miR-573']), verbo([modulates]), complemento([the, activation, of, 'FGFR1-downstream', signaling, in, response, to, fibroblast, growth, factor, 2, '(', 'FGF2)'])]). relacion([sujeto(['Importantly,', we, showed, that, 'GATA3', directly]), verbo([increases]), complemento(['miR-573', 'expression,', and, thus, 'down-regulates', 'FGFR1', 'expression,', 'EMT', and, invasion, of, 'PCa', cells, in, a, 'miR-573-dependent', 'manner,', supporting, the, involvement, of, 'GATA3,', 'miR-573', and, 'FGFR1', in, controlling, the, 'EMT', process, during, 'PCa', metastasis])]). relacion([sujeto(['Altogether,', our, findings, demonstrate, a, novel, mechanism, by, which, 'miR-573']), verbo([modulates]), complemento(['EMT', and, metastasis, of, 'PCa', 'cells,', and, suggest, 'miR-573', as, a, potential, biomarker, 'and/or', therapeutic, target, for, 'PCa', management])]). relacion([sujeto(['Besides', 'E-cadherin', 'loss,', the, best, known, 'ILC', genetic, 'hallmark,', we, identified, mutations]), verbo([targeting]), complemento(['PTEN,', 'TBX3,', and, 'FOXA1', as, 'ILC', enriched, features])]). relacion([sujeto(['PTEN']), verbo([loss]), complemento([associated, with, increased, 'AKT', 'phosphorylation,', which, was, highest, in, 'ILC', among, all, breast, cancer, subtypes])]). relacion([sujeto(['Spatially', clustered, 'FOXA1', mutations, correlated, with]), verbo([increased]), complemento(['FOXA1', expression, and, activity])]). relacion([sujeto(['Conversely,', 'GATA3', mutations, and, high, expression, characterized, luminal, 'A', 'IDC,']), verbo([suggesting]), complemento([differential, modulation, of, 'ER', activity, in, 'ILC', and, 'IDC'])]). relacion([sujeto(['Proliferation', and, 'immune-related', signatures, determined, three, 'ILC', transcriptional, subtypes]), verbo([associated]), complemento([with, survival, differences])]). relacion([sujeto(['Mixed', 'IDC/ILC', cases, were, molecularly, classified, as, 'ILC-like', and, 'IDC-like']), verbo([revealed]), complemento([no, true, hybrid, features])]). relacion([sujeto(['This', multidimensional, molecular, atlas, sheds, new, light, on, the, genetic, bases, of, 'ILC', and]), verbo([provides]), complemento([potential, clinical, options])]). relacion([sujeto(['Adult', 'T', cell, 'leukemia/lymphoma', '(', 'ATL)', is, a, peripheral, 'T', cell, neoplasm, of, largely, unknown, genetic, 'basis,']), verbo([associated]), complemento([with, human, 'T', cell, leukemia, virus, 'type-1', '(', 'HTLV-1)', infection])]). relacion([sujeto(['Here', we, describe, an, integrated, molecular, study, in, which, we, performed, 'whole-genome,', 'exome,', transcriptome, and]), verbo([targeted]), complemento(['resequencing,', as, well, as, 'array-based', copy, number, and, methylation, 'analyses,', in, a, total, of, 426, 'ATL', cases])]). relacion([sujeto(['Other', notable, features, include, a, predominance, of]), verbo([activating]), complemento([mutations, '(', in, 'PLCG1,', 'PRKCB,', 'CARD11,', 'VAV1,', 'IRF4,', 'FYN,', 'CCR4', and, 'CCR7)', and, gene, fusions, '(', 'CTLA4-CD28', and, 'ICOS-CD28)'])]). relacion([sujeto(['We', also, discovered, frequent, intragenic, deletions]), verbo([involving]), complemento(['IKZF2,', 'CARD11', and, 'TP73', and, mutations, in, 'GATA3,', 'HNRNPA2B1,', 'GPR183,', 'CSNK2A1,', 'CSNK2B', and, 'CSNK1A1'])]). relacion([sujeto(['Our', findings, not, only]), verbo([provide]), complemento([unique, insights, into, key, molecules, in, 'T', cell, signaling, but, will, also, guide, the, development, of, new, diagnostics, and, therapeutics, in, this, intractable, tumor])]). relacion([sujeto(['Arrested', development, occurs, in, this, population, and, can]), verbo([lead]), complemento([to, an, accumulation, of, encysted, larvae])]). relacion([sujeto(['This', disease, complex, is]), verbo([caused]), complemento([by, mass, emergence, of, these, larvae, and, is, characterized, by, a, generalized, acute, typhlocolitis, and, manifests, itself, as, a, profuse, 'protein-losing', watery, diarrhea, with, a, reported, 'case-fatality', rate, of, about, 50, '%'])]). relacion([sujeto(['Two', anthelmintic, formulations]), verbo([have]), complemento([a, label, claim, for, larvicidal, therapy, of, these, encysted, 'stages;', moxidectin, and, a, 'five-day', regimen, of, fenbendazole])]). relacion([sujeto(['This', study, revealed, a, subtle, inflammatory, reaction, to, 'moxidectin,', which, is, unlikely, to]), verbo([cause]), complemento([clinical, issues])]). relacion([sujeto(['PELP1', is, a, novel, coregulator, of]), verbo([nuclear]), complemento([hormone, receptors, and, is, implicated, in, playing, a, role, in, driving, breast, cancer, and, enhancing, metastatic, potential])]). relacion([sujeto(['The', 'PELP1', protein, expression, and, potential, role, of, 'PELP1', in, 'triple-negative', breast, carcinoma, '(', 'TNBC)']), verbo([have]), complemento([not, been, well, characterized])]). relacion([sujeto(['We', examined, the, expression, of, 'PELP1', and, 'GATA3', in, 70, primary, 'TNBC', cases, and]), verbo([found]), complemento([that, 'PELP1', had, a, significantly, higher, frequency, of, expression, compared, to, 'GATA3', '(', 96, '%', versus, 46, '%', ;, 'P', &, 'lt;'])]). relacion([sujeto(['Furthermore,', 'PELP1', immunoreactivity, was, consistently]), verbo([maintained]), complemento([in, paired, primary, and, metastatic, 'TNBC', cases, '(', 100, '%', ')'])]). relacion([sujeto(['PELP1', may]), verbo([have]), complemento([diagnostic, utility, for, metastatic, 'TNBC', in, appropriate, 'settings,', such, as, history, of, primary, 'TNBC', in, cases, where, the, primary, is, negative, for, 'GATA3,', 'mammaglobin,', and, 'GCDFP-15'])]). relacion([sujeto(['The', diffuse, and, strong]), verbo([nuclear]), complemento([immunoreactivity, of, 'PELP1', in, most, cases, suggests, that, 'PELP1', may, be, a, molecular, target, for, the, treatment, of, 'TNBC'])]). relacion([sujeto(['We', hope, that, this, study, will]), verbo([provide]), complemento([insights, into, the, role, of, 'PELP1', in, 'TNBC'])]). relacion([sujeto(['The', 'c-Myc', gene, codes, for, a, 'basic-helix-loop-helix-leucine', zipper, transcription, factor, protein, and, is]), verbo([reported]), complemento([to, be, frequently, 'over-expressed', in, human, cancers])]). relacion([sujeto(['Given', that, 'c-Myc', plays, an, essential, role, in, neoplastic, transformation, we, wished, to, define, its, activity, in, lung, cancer, and, therefore, studied, its]), verbo([targeted]), complemento([expression, to, respiratory, epithelium, in, a, transgenic, mouse, disease, model])]). relacion([sujeto(['Using', histological, 'well-defined', 'tumors,', transcriptome, analysis, identified, novel, 'c-Myc', responsive, cell, cycle, and, apoptosis, genes, that, were, validated, as, direct, 'c-Myc']), verbo([targets]), complemento([using, 'EMSA,', 'Western', 'blotting,', gene, reporter, and, 'ChIP', assays])]). relacion([sujeto(['Conversely,', at, promoters, of, genes]), verbo([regulated]), complemento([in, transgenic, but, 'non-carcinomatous', lung, tissue, enriched, binding, sites, for, 'c-Myc,', 'Hbp1,', 'Hif1', were, observed])]). relacion([sujeto(['Bioinformatic', analysis, of, tumor, transcriptomic, data, revealed, regulatory, gene, networks, and, highlighted, mortalin, and, moesin, as, master, regulators, while, gene, reporter, and, 'ChIP', assays, in, the, 'H1299', lung, cancer, cell, line, as, well, as, 'cross-examination', of, published, 'ChIP-sequence', data, of, 7, human, and, 2, mouse, cell, lines]), verbo([provided]), complemento([strong, evidence, for, the, identified, genes, to, be, 'c-Myc', targets])]). relacion([sujeto(['Taken', 'collectively,', a, molecular, circuit, for, 'c-Myc-dependent', cellular, transformation, was, identified, and, the, network, analysis, broadened, the, perspective, for, molecularly]), verbo([targeted]), complemento([therapies])]). relacion([sujeto(['Uterine', cervical, carcinoma, secondarily]), verbo([involving]), complemento([the, genitourinary, tract, is, rarely, documented, histologically])]). relacion([sujeto(['Six', tumors, were]), verbo([found]), complemento([to, be, diffusely, positive, with, 'p16,', 1, tumor, was, 'patchy,', 1, was, 'weak,', and, 2, were, negative])]). relacion([sujeto(['It', is, established, that, the, transcription, factor, 'GATA-3', is]), verbo([induced]), complemento([in, 'Treg', cells, under, inflammatory, conditions])]). relacion([sujeto(['The', mechanism, of, 'GATA-3', in]), verbo([regulating]), complemento(['FOXP3', and, its, relation, to, the, 'IL-6', pathway, remains, unclear])]). relacion([sujeto(['Here', we]), verbo([report]), complemento([how, 'miR-125a-5p', plays, an, important, role, in, regulating, the, conversion, of, 'Treg', cells, by, 'IL-6'])]). relacion([sujeto(['miR-125a-5p', expression, is, low, in, 'Treg', cells, under, steady, state, conditions, and, can, be]), verbo([induced]), complemento([by, 'GATA-3', to, inhibit, the, expression, of, 'IL-6R', and, 'STAT3'])]). relacion([sujeto(['This']), verbo([finding]), complemento([reveals, a, 'GATA3/miR-125a-5p/IL-6R', and, 'STAT3/FOXP3', regulatory, 'pathway,', which, determines, how, 'Treg', cells, respond, to, inflammatory, 'IL-6-rich', conditions])]). relacion([sujeto(['Treatment', with, 1.0, μM, borrelidin]), verbo([suppressed]), complemento([intracellular, lipid, accumulation, by, 80, '%', and, inhibited, the, expression, of, 'adipocyte-specific', genes])]). relacion([sujeto(['Borrelidin']), verbo([suppressed]), complemento([the, mRNA, expression, of, two, master, regulators, of, adipocyte, 'differentiation,', peroxisome, 'proliferator-activated', receptor, gamma, '(', 'PPARγ)', and, 'CCAAT/enhancer', binding, protein, '(', 'C/EBPα)'])]). relacion([sujeto(['Borrelidin']), verbo([increased]), complemento([mRNA, expression, of, negative, regulators, of, differentiation, such, as, 'GATA-binding', protein, '(', 'GATA)', 3, ',', 'Krüppel-like', factor, '(', 'KLF)', 3, and, 'KLF7,', as, well, as, positive, 'regulators,', 'KLF4,', 'KLF6', and, 'KLF15,', at, early, stages, of, differentiation])]). relacion([sujeto(['Borrelidin', significantly]), verbo([inhibited]), complemento([lipid, accumulation, in, control, 'siRNA-treated', 'cells,', and, treatment, with, 'GATA-3', siRNA, slightly, reduced, the, inhibitory, effect, of, borrelidin])]). relacion([sujeto(['These', results, indicate, that, borrelidin]), verbo([inhibited]), complemento([adipocyte, differentiation, partially, via, 'GATA-3'])]). relacion([sujeto(['Previously,', downregulation, of, 'GATA']), verbo([binding]), complemento([protein, 3, '(', 'GATA-3)', was, shown, to, suppress, 'MC', activation, in, an, 'AR', mouse, model])]). relacion([sujeto(['Binding', of, 'microRNA-135a', '(', 'miR-135a)', to, 'GATA-3', was, also, 'observed,', and, overexpression, of, this, miRNA]), verbo([decreased]), complemento(['GATA-3', mRNA, and, protein, expression])]). relacion([sujeto(['In', the, nasal, 'mucosa,', the, expression, of, 'T-box']), verbo([expressed]), complemento([in, 'T', cells, '(', 'T-bet)', was, 'higher,', whereas, that, of, 'GATA-3', was, lower, in, the, 'AR', mice, following, miRNA, treatment])]). relacion([sujeto(['However,', administering, 'miR-135a', to, the, 'AR', mice, appeared, to, balance, this, ratio, by]), verbo([increasing]), complemento([and, decreasing, the, percentage, of, 'Th1', and, 'Th2', 'cells,', respectively])]). relacion([sujeto(['MiR-135a', also, appeared, to, strongly]), verbo([suppress]), complemento([the, infiltration, of, eosinophils, and, 'MCs', into, the, nasal, 'mucosa,', and, it, was, specifically, localized, in, the, 'MCs,', suggesting, that, its, influence, is, modulated, through, regulation, of, 'GATA-3', in, these, cells])]). relacion([sujeto(['Additional', work, identifying, the, full, therapeutic, potential, of, 'miR-135a', in, the, treatment, of, 'AR', and, diseases]), verbo([involving]), complemento(['allergen-induced', inflammation, is, warranted])]). relacion([sujeto(['As', treatment, may, 'differ,', establishing, the, correct, diagnosis, is, paramount, to]), verbo([providing]), complemento([the, appropriate, care, for, these, patients])]). relacion([sujeto(['Induced', pluripotent, stem, cells, '(', 'iPSCs)', undergo, extensive]), verbo([nuclear]), complemento([reprogramming, and, are, generally, indistinguishable, from, embryonic, stem, cells, '(', 'ESCs)', in, their, functional, capacity, and, transcriptome, and, 'DNA', methylation, profiles])]). relacion([sujeto(['However,', direct, conversion, of, cells, from, one, lineage, to, another, often, yields, incompletely, 'reprogrammed,', functionally, compromised, 'cells,', raising, the, question, of, whether, pluripotency, is]), verbo([required]), complemento([to, achieve, a, high, degree, of, nuclear, reprogramming])]). relacion([sujeto(['Here,', we, show, that, transient, expression, of, 'Gata3,', 'Eomes,', and, 'Tfap2c', in, mouse, fibroblasts]), verbo([induces]), complemento(['stable,', 'transgene-independent', trophoblast, 'stem-like', cells, '(', 'iTSCs)'])]). relacion([sujeto([iTSCs, generate, trophoectodermal, lineages, upon, 'differentiation,', form, hemorrhagic, 'lesions,', and, contribute, to, developing, placentas, in, chimera, 'assays,', indicating, a, high, degree, of]), verbo([nuclear]), complemento(['reprogramming,', with, no, evidence, of, passage, through, a, transient, pluripotent, state])]). relacion([sujeto(['Together,', these, data, demonstrate, that, extensive]), verbo([nuclear]), complemento([reprogramming, can, be, achieved, independently, of, pluripotency])]). relacion([sujeto(['Here,', we, show, that, transient, expression, of, 'Tfap2c,', 'Gata3,', 'Eomes,', and, 'Ets2', is, sufficient, to, reprogram, mouse, embryonic, fibroblasts, and, 'post-natal', 'tail-tip-derived', fibroblasts, into]), verbo([induced]), complemento(['TSCs', '(', 'iTSCs)', and, surmount, the, epigenetic, barrier, separating, somatic, from, 'extra-embryonic', lineages])]). relacion([sujeto(['These', findings]), verbo([provide]), complemento([insights, into, the, transcription, factor, networks, governing, 'TSC', identity, and, opportunities, for, studying, the, epigenetic, barriers, underlying, embryonic, and, 'extra-embryonic', lineage, segregation])]). relacion([sujeto(['Genome-wide', association, studies, and, other, genetic, analyses]), verbo([have]), complemento([identified, a, large, number, of, genes, and, variants, implicating, a, variety, of, disease, etiological, mechanisms])]). relacion([sujeto(['We', compiled, a, list, of, genes, functionally]), verbo([interacting]), complemento(['(', 'protein-protein', 'interaction,', or, by, acting, in, the, same, 'pathway)', with, the, master, 'genes,', then, we, surveyed, the, disease, 'connections,', either, by, experimental, evidence, or, by, genetic, association])]). relacion([sujeto(['Embryonic', lethal, genes, '(', also, known, as, essential, 'genes)', are, 'over-represented', in, master, genes, and, their]), verbo([interacting]), complemento([genes, '(', 55, '%', versus, 40, '%', in, other, 'genes)'])]). relacion([sujeto(['Transcription', factors, are, significantly, enriched, among, genes]), verbo([interacting]), complemento([with, the, master, genes, '(', 63, '%', versus, 10, '%', in, other, 'genes)'])]). relacion([sujeto(['Disease-connected', genes, are, enriched, in, this, list, of, 'genes:', 42, '%', of, these, genes]), verbo([have]), complemento([a, disease, connection, according, to, 'Online', 'Mendelian', 'Inheritance', in, 'Man', '(', 'OMIM)', '(', versus, 23, '%', in, other, 'genes),', and, 74, '%', are, associated, with, some, diseases, or, phenotype, in, a, 'Genome', 'Wide', 'Association', 'Study', '(', 'GWAS)', '(', versus, 43, '%', in, other, 'genes)'])]). relacion([sujeto(['Seemingly,', not, all, of, the, diseases, connected, to, genes, surveyed, were, immune, 'related,', which, may, indicate, pleiotropic, functions, of, the, master, regulator, genes, and]), verbo([associated]), complemento([genes])]). relacion([sujeto(['In', 'addition,', a, marked]), verbo([decrease]), complemento([in, plasma, 'IL-4', levels, was, observed, in, the, 'GD', group])]). relacion([sujeto(['Furthermore,', a, clear, correlation, between]), verbo([increased]), complemento(['IFN-γ', mRNA, expression, and, 'IFN-γ', '(', 'P<0'])]). relacion([sujeto(['Therefore', while, able, to, profoundly, influence, the, proliferation, and, function, of, other, 'MEC', 'populations,', 'HS-MECs', are, purported, not, to]), verbo([respond]), complemento([to, sex, hormone, signals, by, engaging, in, significant, cell, proliferation, during, adulthood])]). relacion([sujeto(['This', is, a, convenient, and, practical, simplification, that, overshadows, the, 'sublime,', and, potentially, 'critical,', phenotypic, plasticity]), verbo([found]), complemento([within, the, adult, 'HS-MEC', population])]). relacion([sujeto(['This', concept, is, exemplified, by, the, large, proportion, '(', '~80 %)', of, human, breast, cancers]), verbo([expressing]), complemento(['PGR', 'and/or', 'ERα,', demonstrating, that, 'HS-MECs', clearly, proliferate, in, the, context, of, breast, cancer])]). relacion([sujeto(['Understanding', how, 'HS-MEC', proliferation, and, differentiation, is, driven, could, be, key, to, unraveling, the, mechanisms, behind, uncontrolled, 'HS-MEC', proliferation]), verbo([associated]), complemento([with, 'ERα-', 'and/or', 'PGR-positive', breast, cancers])]). relacion([sujeto(['Protein', abundance, must, be, precisely]), verbo([regulated]), complemento([throughout, 'life,', and, nowhere, is, the, stringency, of, this, requirement, more, evident, than, during, 'T-cell', 'development:', 'A', twofold, increase, in, the, abundance, of, transcription, factor, 'GATA3', results, in, thymic, 'lymphoma,', while, reduced, 'GATA3', leads, to, diminished, 'T-cell', production])]). relacion([sujeto(['GATA3', haploinsufficiency, also]), verbo([causes]), complemento([human, 'HDR', '(', 'hypoparathyroidism,', 'deafness,', and, renal, 'dysplasia)', 'syndrome,', often, accompanied, by, immunodeficiency])]). relacion([sujeto(['Here', we, show, that]), verbo([loss]), complemento([of, one, 'Gata3', allele, leads, to, diminished, expansion, '(', and, compromised, 'development)', of, immature, 'T', cells, as, well, as, aberrant, induction, of, myeloid, transcription, factor, 'PU'])]). relacion([sujeto(['This', effect, is, at, least, in, part]), verbo([mediated]), complemento(['transcriptionally:', 'We', discovered, that, 'Gata3', is, monoallelically, expressed, in, a, parent, of, 'origin-independent', manner, in, hematopoietic, stem, cells, and, early, 'T-cell', progenitors])]). relacion([sujeto(['We', show, that, the, 'monoallelic-to-biallelic', transcriptional, switch, is, stably]), verbo([maintained]), complemento([and, therefore, is, not, a, stochastic, phenomenon])]). relacion([sujeto(['This', unique, 'mechanism,', if, adopted, by, other, regulatory, 'genes,', may]), verbo([provide]), complemento([new, biological, insights, into, the, rather, prevalent, phenomenon, of, monoallelic, expression, of, autosomal, genes, as, well, as, into, the, variably, penetrant, pathophysiological, spectrum, of, phenotypes, observed, in, many, human, syndromes, that, are, due, to, haploinsufficiency, of, the, affected, gene])]). relacion([sujeto(['To', identify, differentially]), verbo([expressed]), complemento(['T', 'cells-related', genes, in, peripheral, blood, mononuclear, cells, and, compare, their, differences, in, 'T', cell, activation, and, subset, functions, in, different, stages, of, coronary, atherosclerosis, disease, '(', 'CAD)'])]). relacion([sujeto([20, patients, with, acute, myocardial, infarction, patients, '(', 'AMI),', 20, patients, with, stable, angina, pectoris, '(', 'SA)', and, 20, healthy, volunteers, were]), verbo([recruited]), complemento([into, the, study])]). relacion([sujeto([mRNA, expression, of, 68, genes]), verbo([involved]), complemento([in, 'T', cell, was, detected])]). relacion([sujeto(['Then', improving, 'T', cell]), verbo([mediated]), complemento([cellular, immunity, may, be, considered, as, a, potential, target, for, medical, interventions, in, the, patients, with, 'AMI'])]). relacion([sujeto([1, is, predominantly]), verbo([expressed]), complemento([in, dendritic, cells, '(', 'DCs)', and, is, essential, for, 'DC', differentiation])]). relacion([sujeto(['Although', there, are, several]), verbo([reports]), complemento([that, 'PU'])]). relacion([sujeto([1, positively]), verbo([regulates]), complemento([the, expression, of, 'DC-specific', 'genes,', whether, 'PU'])]). relacion([sujeto([1, also]), verbo([has]), complemento([a, suppressive, effect, on, 'DCs', is, largely, unknown])]). relacion([sujeto([1]), verbo([suppresses]), complemento([the, expression, of, 'Th2', cytokines, including, 'IL-13', and, 'IL-5', in, bone, 'marrow-derived', 'DCs', '(', 'BMDCs),', through, repression, of, the, expression, of, 'GATA3,', which, is, a, master, regulator, of, 'Th2', differentiations])]). relacion([sujeto([1, siRNA, was, introduced, into, 'BMDCs,', 'LPS-induced', expression, of, 'IL-13', and, 'IL-5', was]), verbo([increased]), complemento([along, with, upregulation, of, the, constitutive, expression, of, 'GATA2', and, 'GATA3'])]). relacion([sujeto([1]), verbo([bound]), complemento([to, 'Gata3', proximal, promoter, 'region,', which, is, more, dominant, than, the, distal, promoter, in, driving, 'GATA3', transcription, in, 'DCs'])]). relacion([sujeto(['The', degree, of, histone, acetylation, at, the, 'Gata3', promoter, was]), verbo([decreased]), complemento([in, 'PU'])]). relacion([sujeto([1, 'siRNA-introduced', 'DCs,']), verbo([suggesting]), complemento([the, involvement, of, 'PU'])]). relacion([sujeto(['Treatment', with, a, histone, deacetylase, '(', 'HDAC)', 'inhibitor,', trichostatin, 'A,']), verbo([increased]), complemento([the, degree, of, histone, 'H3', acetylation, at, the, 'Gata3', promoter, and, induced, the, subsequent, expression, of, 'GATA3'])]). relacion([sujeto(['Experiments', using, 'HDAC', inhibitors, and, siRNAs, showed, that, 'HDAC3']), verbo([suppressed]), complemento(['GATA3', expression])]). relacion([sujeto(['The', recruitment, of, 'HDAC3', to, the, 'Gata3', promoter, was]), verbo([decreased]), complemento([by, 'PU'])]). relacion([sujeto(['LPS-induced', 'IL-13', expression, was, dramatically, reduced, in, 'BMDCs', generated, from, mice, lacking, the]), verbo([conserved]), complemento(['GATA3', response, 'element,', termed, 'CGRE,', which, is, an, essential, site, for, the, binding, of, 'GATA3', on, the, 'Il-13', promoter])]). relacion([sujeto(['The', degree, of, 'H3K4me3', at, 'CGRE', was, significantly]), verbo([increased]), complemento([in, 'PU'])]). relacion([sujeto([1, 'siRNA-transfected']), verbo([stimulated]), complemento(['DCs'])]). relacion([sujeto(['HANABA', 'TARANU', '(', 'HAN)', encodes, a, 'GATA3-type', transcription, factor, that, functions, in, floral, organ, 'development,', 'SAM', 'organization,', and, embryo, development, in, 'Arabidopsis,', but, is]), verbo([involved]), complemento([in, suppressing, bract, outgrowth, and, promoting, branching, in, grass, species])]). relacion([sujeto(['CsHAN1', is, predominantly]), verbo([expressed]), complemento([at, the, junction, of, the, 'SAM', and, the, 'stem,', and, can, partially, rescue, the, 'han-2', floral, organ, phenotype, in, 'Arabidopsis'])]). relacion([sujeto(['Further,', it, was]), verbo([found]), complemento([that, 'CsHAN1', may, regulate, 'SAM', development, through, regulating, the, 'WUSCHEL', '(', 'WUS)', and, 'SHOOT', 'MERISTEMLESS', '(', 'STM)', 'pathways,', and, mediate, leaf, development, through, a, complicated, gene, regulatory, network, in, cucumber])]). relacion([sujeto(['Effector', 'CD4', 'T', cell, lineages]), verbo([have]), complemento([been, implicated, as, potent, inducers, of, autoimmune, diseases])]). relacion([sujeto(['Tbet,', 'Gata3', and, 'Rorgt', are, master, transcriptional, regulators, of, 'Th1,', 'Th2', and, 'Th17', lineages, respectively, and]), verbo([promote]), complemento([the, distinct, expression, of, signature, cytokines])]). relacion([sujeto(['Significant', progress]), verbo([has]), complemento([been, made, in, understanding, the, transcriptional, network, that, drives, 'CD4', 'T', cell, 'differentiation,', revealing, novel, points, of, regulation, mediated, by, transcription, 'factors,', cell, surface, 'receptors,', cytokines, and, chemokines])]). relacion([sujeto(['The', transcription, factor, 'GATA3', is, a, recently, described, biomarker, that, is, highly]), verbo([expressed]), complemento([in, bladder, and, breast, carcinomas])]). relacion([sujeto(['Although', it]), verbo([has]), complemento([shown, sensitivity, as, a, marker, of, primary, bladder, carcinomas, with, purely, urothelial, 'differentiation,', the, ability, of, 'GATA3', to, label, primary, bladder, carcinomas, with, variant, morphologic, patterns, has, been, incompletely, assessed, to, date])]). relacion([sujeto(['The', current, study, was, designed, to, determine, whether, 'GATA3', staining, is]), verbo([retained]), complemento([in, &, 'quot;unconventional"', bladder, carcinomas])]). relacion([sujeto(['We', herein, present, the, first, 'Turkish', patient, with, 'HDR', 'syndrome,', who]), verbo([has]), complemento([a, p])]). relacion([sujeto(['This']), verbo([report]), complemento([indicates, that, p])]). relacion([sujeto(['β1,4-Galactosylransferases', are, a, family, of, enzymes, encoded, by, seven, 'B4GALT', genes, and, are]), verbo([involved]), complemento([in, the, development, of, anticancer, drug, resistance, and, metastasis])]). relacion([sujeto(['The', 'TR1-PE1', showed, unique, dinucleotide, 'base-stacking', energy, values, specific, to, transcription, factor]), verbo([binding]), complemento([sites, '(', 'TFBSs),', 'INR', and, 'BRE,', and, harbored, 'CpG', 'Island', '(', 'CGI)', that, showed, 'GC', skew, with, potential, for, 'R-loop', formation, at, the, transcription, starting, sites, '(', 'TSSs)'])]). relacion([sujeto(['We']), verbo([suggest]), complemento([that, the, unique, expression, patterns, for, the, 'B4GALT1', in, normal, and, malignant, tissues, are, controlled, by, a, differential, usage, of, 5, '\'', -, 'B4GALT1', regulatory, units, along, with, a, 'post-transcriptional', regulation, by, the, antisense, 'RNA,', which, in, turn, govern, the, 'cell-matrix', 'interactions,', neoplastic, 'progression,', anticancer, drug, 'sensitivity,', and, could, be, utilized, in, personalized, therapy])]). relacion([sujeto(['The', notion, that, 'GATA3', expression, is]), verbo([required]), complemento([for, the, differentiation, and, maintenance, of, normal, breast, tissue, has, been, well, established])]). relacion([sujeto(['Recently,', 'GATA3', is]), verbo([found]), complemento([to, actively, participate, in, the, multistep, process, leading, breast, cancer, 'pathogenesis,', including, 'tumorigenesis,', tumor, 'differentiation,', epithelial, mesenchymal, 'transition,', and, metastasis, through, regulation, of, various, target, genes])]). relacion([sujeto(['On', the, other, 'hand,', several, studies]), verbo([have]), complemento([raised, questions, and, highlighted, the, role, of, 'GATA3-low', or, 'GATA3-negative', cells, during, the, malignant, development, of, breast, cancer])]). relacion([sujeto(['In', addition, to, gene, 'expression,', 'GATA3', mutations]), verbo([provide]), complemento([another, dimension, of, complexity])]). relacion([sujeto(['As', one, of, the, most, frequently, mutated, genes, in, breast, 'cancer,', 'GATA3', mutations, may]), verbo([have]), complemento([an, effect, on, 'DNA-binding', 'ability,', protein, 'production,', and, transactivation, activity])]). relacion([sujeto(['Estradiol', '(', 'E2', ')', deficiency, can]), verbo([cause]), complemento([bone, loss, and, the, skew, of, 'Th1/Th2', cells])]). relacion([sujeto(['However,', the, correlation, between, the, 'Th1/Th2', cells, and, the, bone]), verbo([loss]), complemento([induced, by, estrogen, deficiency, remains, unclear])]). relacion([sujeto(['Our', aim, was, to, investigate, the, role, of, 'Th1/Th2', in, bone]), verbo([loss]), complemento([induced, by, estrogen, deficiency, and, elucidated, the, therapeutical, effect, of, catalpol, in, this, condition])]). relacion([sujeto(['Catalpol', alleviated, bone]), verbo([loss]), complemento([effectively, by, regulating, 'Th1/Th2', polarization])]). relacion([sujeto(['Catalpol']), verbo([promoted]), complemento([the, expression, of, 'Th2-specific', transcription, factors, while, inhibited, that, associated, with, 'Th1'])]). relacion([sujeto(['Th1/Th2', skew, is]), verbo([involved]), complemento([in, bone, loss, induced, by, estrogen, deficiency])]). relacion([sujeto(['Catalpol', alleviates, bone]), verbo([loss]), complemento([effectively, by, regulating, 'Th1/Th2', paradigm])]). relacion([sujeto(['Transcription', factors, '(', 'TFs)']), verbo([regulate]), complemento(['cell-type-specific', gene, expression, programs, by, combinatorial, binding, to, 'cis-genomic', 'elements,', particularly, 'enhancers,', subsequently, leading, to, the, recruitment, of, 'cofactors,', and, the, general, transcriptional, machinery, to, target, genes])]). relacion([sujeto(['Using', data, integration, of, 'genome-wide', 'TF']), verbo([binding]), complemento(['profiles,', we, defined, regions, with, combinatorial, binding, of, 'lineage-specific', master, 'TFs', '(', 'T-BET,', 'GATA3,', and, 'ROR-γt)', and, 'STATs', '(', 'STAT1', and, 'STAT4,', 'STAT6,', and, 'STAT3)', in, murine, 'T', helper, '(', 'Th)', 1, ',', 'Th2,', and, 'Th17', 'cells,', respectively])]). relacion([sujeto(['Stringently', excluding, promoter, 'regions,', we, revealed, precise, genomic, elements, which, were, preferentially]), verbo([associated]), complemento([with, the, enhancer, marks, p300, and, 'H3K4me1'])]). relacion([sujeto(['Genes']), verbo([associated]), complemento([with, 'super-enhancers,', including, relevant, 'Th-cell', genes, '(', such, as, 'Ifng', in, 'Th1,', 'Il13', in, 'Th2,', and, 'Il17a', in, 'Th17', 'cells),', showed, strong, transcriptional, activity])]). relacion([sujeto(['Altogether,', the, discovered, catalog, of, enhancers]), verbo([provides]), complemento([information, about, crucial, 'Th-cell', 'subtype-specific', regulatory, 'hubs,', which, will, be, useful, for, revealing, 'cell-type-specific', gene, regulation, processes])]). relacion([sujeto(['Although', numerous, efforts]), verbo([have]), complemento([been, 'made,', the, pathogenesis, underlying, lung, 'squamous-cell', carcinoma, '(', 'SCC)', remains, unclear])]). relacion([sujeto(['A', higher, burden, of, the, 'CNVs', was]), verbo([found]), complemento([in, 10, -, 50, kb, length])]). relacion([sujeto(['Furthermore,', 38, 'TFs', were, screened, for, the, 9, 'CNV-driven', genes, and, then, the, regulatory, network, was, 'constructed,', in, which, the, 'GATA-binding', factor, 1, ',', 2, ',', and, 3, '(', 'GATA1,', 'GATA2,', 'GATA3)', jointly]), verbo([regulated]), complemento([the, expression, of, 'TP63'])]). relacion([sujeto(['Accumulating', evidence]), verbo([has]), complemento([established, that, 'IL-35', plays, an, important, role, in, the, regulation, of, immune, 'homeostasis,', but, little, is, known, regarding, the, function, of, 'IL-35', in, acquired, aplastic, anemia, '(', 'AA)'])]). relacion([sujeto(['Our', study, demonstrated, that, significantly]), verbo([decreased]), complemento([plasma, levels, of, 'IL-35', in, 'AA', were, closely, correlated, with, disease, severity])]). relacion([sujeto(['In', vitro, stimulation, experiment, further, confirmed, the, 'anti-inflammatory', effects, of, 'IL-35,', including]), verbo([suppressing]), complemento([the, proliferation, of, 'CD4(+)', and, 'CD8(+)', effector, 'T', 'cells,', inhibiting, the, secretion, of, 'interferon-γ,', tumor, necrosis, 'factor-α', and, 'IL-17', and, promoting, the, production, of, transforming, growth, 'factor-β', by, peripheral, blood, mononuclear, cells, from, patients, with, 'AA'])]). relacion([sujeto(['Furthermore,', we, established, that, 'IL-35']), verbo([inhibited]), complemento([the, differentiation, of, type, 1, 'T', cells, and, 'T', helper, 17, cells, but, promoted, the, differentiation, of, type, 2, 'T', cells])]). relacion([sujeto(['Accordingly,', the, expression, of, 'T-bet', and, 'RORγt', was]), verbo([inhibited]), complemento([while, the, expression, of, 'GATA3', was, induced, after, 'IL-35', treatment])]). relacion([sujeto(['In', 'summary,', our, findings]), verbo([suggested]), complemento([that, decreased, 'IL-35', might, contribute, to, the, loss, of, 'immune-tolerance', and, be, critically, involved, in, the, pathogenesis, of, 'AA'])]). relacion([sujeto(['This', study, tested, the, utility, of, trefoil, factor, 1, '(', 'TFF1)', for, this, purpose, and, compared, it, with, mammaglobin, and, 'GATA', protein]), verbo([binding]), complemento([3, '(', 'GATA-3)'])]). relacion([sujeto(['GATA3', plays, a, role, in, cell, proliferation, and, differentiation, in, many, 'tissues,', including, 'breast,', and, it]), verbo([has]), complemento([been, suggested, that, 'GATA3', expression, correlates, with, 'ER', expression])]). relacion([sujeto(['We', describe, the, case, of, a, 21, -, 'year-old', male, with, 'hypocalcaemia,', 'hyperphosphataemia,', recurrent, limb, 'twitch,', 'deafness,', 'proteinuria,']), verbo([increased]), complemento([serum, creatinine, and, urea, nitrogen, 'levels,', and, shrinkage, of, both, kidneys])]). relacion([sujeto(['We']), verbo([provide]), complemento([further, evidence, that, 'HDR', syndrome, is, caused, by, haploinsufficiency, of, 'GATA3'])]). relacion([sujeto(['Here', we, present, the, first, case, of, one, such, tumor]), verbo([associated]), complemento([with, an, exophyic, 'Schneiderian', papilloma])]). relacion([sujeto(['Biopsy']), verbo([suggested]), complemento(['adenocarcinoma,', at, least, in, situ, and, the, patient, subsequently, underwent, complete, resection])]). relacion([sujeto(['Pathologic', evaluation, demonstrated, polypoid, tumor, consistent, with, a, 'low-grade', papillary, adenocarcinoma, with, micropapillary, architecture]), verbo([associated]), complemento([with, a, small, amount, of, residual, exophytic, 'Schneiderian', papilloma])]). relacion([sujeto(['We', still]), verbo([have]), complemento([no, understanding, on, why, only, some, 'DCIS', lesions, evolve, to, invasive, cancer, whereas, others, appear, not, to, do, so, during, the, life, span, of, the, patient])]). relacion([sujeto(['Significantly,', 83, '%', of, lesions, displayed, numerous, large, chromosomal, copy, number, 'alterations,']), verbo([suggesting]), complemento([they, might, precede, selection, of, cancer, driver, mutations])]). relacion([sujeto(['The', more, aggressive, 'DCIS-C1', '(', highly, 'proliferative,', 'basal-like,', or, 'ERBB2(+))', displayed, signatures, characteristic, of]), verbo([activated]), complemento(['Treg', cells, '(', 'CD4(+)/CD25(+)/FOXP3(+))', and, 'CTLA4(+)/CD86(+)', complexes, indicative, of, a, 'tumor-associated', immunosuppressive, phenotype])]). relacion([sujeto(['Cytokines']), verbo([have]), complemento([been, identified, as, the, major, stimuli, driving, 'ILC2', activation, and, expansion])]). relacion([sujeto(['ILC2s', display, high, expression, of, inducible, 'T-cell', costimulator, '(', 'ICOS),', which, belongs, to, the, 'CD28', 'superfamily,', and, which]), verbo([has]), complemento([been, shown, to, control, late, effector, 'T-cell', 'functions,', and, is, of, utmost, importance, for, the, humoral, immune, response])]). relacion([sujeto(['Here,', we, show, that, 'ICOS', signaling, in, mice]), verbo([regulates]), complemento(['ILC2', homeostasis, independently, of, 'T', cells, and, 'B', 'cells,', by, promoting, proliferation, and, accumulation, of, mature, 'ILC2s', in, lung, and, intestine])]). relacion([sujeto(['Our', data, identify, a, role, of, 'ICOS', in, innate, immunity, and, indicate, that, not, only, 'cytokines,', but, also, costimulatory, pathways, such, as, those]), verbo([involving]), complemento(['ICOS,', can, contribute, to, regulate, the, 'ILC2', pool])]). relacion([sujeto(['Thus,', 'ICOS', costimulation, 'blockade,', which, is, currently, under, clinical, evaluation, for]), verbo([inhibiting]), complemento([the, humoral, immune, 'response,', could, also, target, innate, inflammatory, circuits])]). relacion([sujeto(['There', are, few, available, discriminating, immunohistochemical, markers, as, squamous, differentiation, typically]), verbo([leads]), complemento([to, loss, of, expression, of, characteristic, primary, epithelial, cell, markers, of, both, breast, and, lung, origin])]). relacion([sujeto(['GATA', protein]), verbo([binding]), complemento([3, '(', 'GATA-3)', is, a, useful, marker, of, breast, origin, in, metastatic, ductal, and, lobular, carcinomas, including, poorly, differentiated, 'triple-negative', carcinomas, and, some, metaplastic, carcinomas])]). relacion([sujeto(['This']), verbo([suggests]), complemento([that, immunoreactivity, for, 'ER', and, 'GATA-3', may, support, a, diagnosis, of, metastatic, 'SCC', in, the, context, of, a, prior, metaplastic, 'SCC', of, the, breast])]). relacion([sujeto(['Typical', histologic, features, of, the, lipid, cell, variant, include, 'lipoblast-like', cells, with, a, notched]), verbo([nuclear]), complemento(['appearance,', abundant, 'vacuoles,', an, eccentric, 'nucleus,', and, pagetoid, spread, in, some, areas])]). relacion([sujeto(['Type', 2, innate, lymphoid, cells, '(', 'ILC2s)']), verbo([promote]), complemento(['anti-helminth', responses, and, contribute, to, allergies])]). relacion([sujeto(['Here,', we]), verbo([report]), complemento([that, 'Bcl11b,', previously, considered, a, 'T-cell-specific', transcription, 'factor,', acted, directly, upstream, of, the, key, 'ILC2', transcription, factor, 'Gfi1', to, maintain, its, expression, in, mature, 'ILC2s'])]). relacion([sujeto(['Thus,', 'Bcl11b(-/-)', 'ILC2s', lost, their, functions, and, gained, 'ILC3', 'functions,', and, although, they, expanded, in, response, to, the, protease, allergen, 'papain,', they, produced, 'ILC3', but, not, 'ILC2', cytokines, and]), verbo([caused]), complemento([increased, airway, infiltration, of, neutrophils, instead, of, eosinophils])]). relacion([sujeto(['Transforming', growth, factor, '(', 'TGF)-β', and, interleukin, '(', 'IL)-13', play, a, crucial, role, in, the, pathogenesis, of, systemic, sclerosis, '(', 'SSc),', partly, through, activation, of, collagen, production, that]), verbo([leads]), complemento([to, fibrosis])]). relacion([sujeto(['The', involvement, of, 'Smad', and, 'GATA-3', transcription, factors, was, assessed, by, using, specific, inhibitors, and, small, interfering, 'RNA,', and, the]), verbo([binding]), complemento([capacity, of, 'GATA-3', to, the, 'IL-13', gene, promoter, was, evaluated, by, chromatin, immunoprecipitation, assay])]). relacion([sujeto(['TGF-β']), verbo([induced]), complemento([a, significant, decrease, in, 'IL-13', mRNA, and, protein, levels, in, lymphocytes, from, healthy, donors, '(', mean, '[', '±SD]', inhibition, of, 30, '%', ±, 10, '%', and, 20, '%', ±, 7, '%', ',', 'respectively;', p, &, 'lt;', 0.05, ')'])]). relacion([sujeto(['In', 'contrast,', 'TGF-β']), verbo([promoted]), complemento([a, significant, increase, in, 'IL-13', mRNA, levels, and, 'IL-13', synthesis, by, 'CD4(+)', and, 'CD8(+)', 'T-cell', subtypes, from, patients, with, 'SSc,', with, respective, increases, of, 2.4, ±, 0.3, -, 'fold,', 1.6, ±, 0.05, -, fold, and, 2.7, ±, 0.02, -, fold])]). relacion([sujeto(['The', involvement, of, the, 'Smad', signaling, pathway, and, upregulation, of, 'GATA-3']), verbo([binding]), complemento([capacity, on, the, 'IL-13', promoter, in, lymphocytes, from, patients, with, 'SSc', contributed, to, the, effect, of, 'TGF-β', on, 'IL-13', production])]). relacion([sujeto(['These', results, demonstrate, that, 'TGF-β', upregulates, 'IL-13', synthesis, through, 'GATA-3', expression, in, the, 'T', lymphocytes, of, patients, with, 'SSc,', confirming, that, the, 'GATA-3', transcription, factor, can, be, regarded, as, a, novel, therapeutic]), verbo([target]), complemento([in, patients, with, 'SSc'])]). relacion([sujeto(['However,', the, role, of, 'IL-35,', a, novel, member, of, the, 'IL-12', cytokine, 'family,', in, this, kind, of, disease]), verbo([has]), complemento([not, yet, been, elucidated])]). relacion([sujeto(['This', study]), verbo([involved]), complemento([21, 'GBS', patients, and, an, equal, number, of, healthy, controls, '(', 'HCs)'])]). relacion([sujeto(['In', 'contrast,', the, levels, of, 'STAT5', and, 'STAT6', proteins, and, 'GATA3,', 'Foxp3,', 'IL-4', and, 'TGF-β1', mRNAs, were]), verbo([decreased]), complemento([in, 'GBS', patients, in, comparison, with, those, of, 'HCs'])]). relacion([sujeto(['In', 'addition,', treatment, of, 'CD4+', 'T', cells, from, 'GBS', patients, with, 'IL-35', upregulated, 'IL-35,', 'STAT5', and, 'STAT6', protein, and, 'T-bet,', 'GATA3,', 'Foxp3,', 'IFN-γ,', 'IL-4,', 'IL-17A', and, 'TGF-β1', mRNA, while]), verbo([inhibited]), complemento([levels, of, 'STAT3', and, 'STAT4', protein, and, 'RORγt', and, 'IL-17A', mRNA])]). relacion([sujeto(['Further', studies, are]), verbo([required]), complemento([in, order, to, evaluate, its, role, in, 'GBS'])]). relacion([sujeto(['Tim-3', is, considered, as, one, of, the, 'T-cell', immunoglobulin, mucin, '(', 'TIM)', gene, family, 'members,', which, contributes, to, the]), verbo([activating]), complemento([or, silencing, 'genes,', but, the, mechanism, of, 'Tim-3', function, in, mediating, 'SLE', or, tumor, metastasis, has, not, been, well, explored])]). relacion([sujeto(['Here,', we]), verbo([reported]), complemento(['Tim-3', was, high, expressed, in, the, peripheral, blood, mononuclear, cells, '(', 'PBMCs)', of, patients, with, 'SLE,', detected, by, 'RT-PCR,', 'significantly,', 'GATA-3', mRNA, expression, also, increased, in, patients, with, 'SLE,', compared, with, the, healthy, control, groups])]). relacion([sujeto(['The', bioinformatics, used, to, detect, the, 'TCGA', database, indicated, the, abnormal, expression, of, 'Tim-3', was]), verbo([involved]), complemento([in, several, different, cancer, types])]). relacion([sujeto(['Further,', two, kinds, of, relative, 'Tim-3', siRNAs, in, ccRCC, cell, lines]), verbo([inhibit]), complemento([cell, migration, and, invasion, in, 'vitro,', 'However,', the, inhibition, could, be, partially, rescued, by, the, additional, 'GATA3', knockdown])]). relacion([sujeto(['Further,', the, down, regulation, in, the, 'RNA', and, protein, levels, of, 'GATA3,', and, the, negative, correlation, between, 'Tim-3', and, 'GATA3', implied, that, suppression, of, downstream, 'GATA3', was, an, important, mechanism, by, which, 'Tim-3']), verbo([triggered]), complemento([metastasis, in, ccRCC, cell, lines])]). relacion([sujeto(['Together,', our, experiments]), verbo([reveal]), complemento([the, role, for, 'Tim-3', in, facilitating, 'SLE', or, invasive, potential, of, ccRCC, cells, by, either, activating, 'GATA3', or, inhibiting, 'GATA3,', suggesting, that, 'Tim-3', might, be, a, potential, therapeutic, target, for, treating, 'SLE', or, clear, cell, renal, cell, carcinoma])]). relacion([sujeto(['TGF-β/Smad3', signaling, is, a, key, pathway, in]), verbo([regulating]), complemento(['T', cell, development])]). relacion([sujeto(['We']), verbo([report]), complemento([here, that, 'Smad3', is, a, key, transcriptional, factor, of, 'TGF-β', signaling, that, differentially, regulates, 'T', cell, immune, responses, in, a, mouse, model, of, cardiac, allograft, rejection, in, which, donor, hearts, from, 'BALB/c', mice, were, transplanted, into, 'Smad3', knockout, '(', 'KO)', and, wild, type, '(', 'WT)', mice])]). relacion([sujeto(['This', allograft, protection, was]), verbo([associated]), complemento([with, a, significant, inhibition, of, proinflammatory, cytokines, '(', 'IL-1β,', 'TNF-α,', and, 'MCP-1)', and, infiltration, of, 'neutrophils,', 'CD3+', 'T', 'cells,', and, 'F4/80+', macrophages])]). relacion([sujeto(['Importantly,', deletion, of, 'Smad3', markedly]), verbo([suppressed]), complemento(['T-bet', and, 'IFN-γ', while, enhancing, 'GATA3', and, 'IL-4', 'expression,', resulting, in, a, shift, from, the, 'Th1', to, 'Th2', immune, responses])]). relacion([sujeto(['Loss', of, 'Smad3', results, in, a, shift, from, 'Th1', to, 'Th2', but]), verbo([suppressing]), complemento(['Th17', immune, responses])]). relacion([sujeto(['Mutations', in, 'OPG', are]), verbo([involved]), complemento([in, a, variety, of, human, diseases])]). relacion([sujeto(['We']), verbo([have]), complemento([shown, that, cochlear, spiral, ganglion, cells, secrete, 'OPG', at, high, levels, and, lack, of, 'OPG', causes, sensorineural, hearing, loss, in, addition, to, the, previously, described, conductive, hearing, loss])]). relacion([sujeto(['In', order, to, study, the, regulation, of, 'OPG', 'expression,', we, conducted, a, database, search, on, regulatory, elements, in, the, promoter, region, of, the, 'OPG', 'gene,', and, identified, two, potential, 'GATA-3']), verbo([binding]), complemento([sites])]). relacion([sujeto(['The', expression, of, wild, type, 'GATA-3']), verbo([activated]), complemento(['OPG', mRNA, and, protein, 'expression,', while, the, expression, of, a, dominant, negative, mutant, of, 'GATA-3', or, a, 'GATA-3', shRNA, construct, reduced, 'OPG', mRNA, and, protein, levels])]). relacion([sujeto(['GATA-3', deficient, cells, generated, by]), verbo([expressing]), complemento([a, 'GATA-3', shRNA, construct, were, sensitive, to, apoptosis, induced, by, etoposide, and, 'TNF-α'])]). relacion([sujeto(['This', apoptotic, effect, could, be, partly]), verbo([prevented]), complemento([by, the, 'co-treatment', with, exogenous, 'OPG'])]). relacion([sujeto(['Our', results]), verbo([suggest]), complemento([new, approaches, to, rescue, diseases, due, to, 'GATA-3', deficiency, -, such, as, in, 'hypoparathyroidism,', sensorineural, 'deafness,', and, renal, '(', 'HDR)', syndrome, -, by, 'OPG', therapy])]). relacion([sujeto(['Boswellic', acid, may, improve, asthma, symptoms, by]), verbo([inhibiting]), complemento([pSTAT6, 'expression,', which, consequently, reduces, 'GATA3', expression])]). relacion([sujeto(['Fewer', than, 10, cases]), verbo([have]), complemento([been, 'reported,', and, our, aim, was, to, determine, the, clinical, and, pathological, features, of, a, series, of, tumours, from, a, specialized, uropathology, laboratory])]). relacion([sujeto(['Immunostaining', performed, on, 10, &, 'nbsp;cases', showed, uniform, positivity, for, 'CK', 8, /, 18, and, 'AE1/AE3,', while, most, tumours, were, positive, for, 'CK7,', 'CK20,', uroplakin, 'III', and, 'GATA']), verbo([binding]), complemento([protein, 3, '(', 'GATA3)'])]). relacion([sujeto(['The', association, of, 'PGCC', with, 'UC', and, an, overlap, in, immunoexpression]), verbo([suggests]), complemento([that, 'PGCC', represents, an, extreme, form, of, 'UC', 'de-differentiation'])]). relacion([sujeto(['Clinical', improvement, of, psoriasis]), verbo([induced]), complemento([by, 'IL-4', treatment, has, been, ascribed, to, changes, in, dermal, inflammatory, 'cells,', such, as, activation, of, 'Th2', cells, and, tolerization, of, dendritic, cells, by, suppressing, 'IL-23', production])]). relacion([sujeto(['The', pathologic, epidermal, alterations, in, psoriatic, lesional, skin, include]), verbo([increased]), complemento([epidermal, expression, of, 'IL-1β,', 'IL-6,', 'S100A7,', and, human, 'β-defensin', 2, '(', 'hBD2)', and, a, downregulated, expression, of, the, epidermal, transcription, factor, 'GATA3'])]). relacion([sujeto(['The', secretion, of, 'IL-1β', and, 'IL-6', by, psoriatic, epidermal, cells, was]), verbo([inhibited]), complemento([by, 'IL-4', via, transcriptional, and, posttranscriptional, 'mechanisms,', respectively])]). relacion([sujeto(['In', normal, 'skin,', 'IL-4']), verbo([inhibited]), complemento(['IL-1β-', and, 'IL-17A-induced', hBD2, expression, in, vitro])]). relacion([sujeto(['In', 'addition,', 'IL-4', reduced, the, protein, expression, of, hBD2, in, psoriatic, skin, biopsies, and]), verbo([induced]), complemento(['phospho-STAT6', protein])]). relacion([sujeto(['An', important, portion, of, asthmatics, do, not]), verbo([respond]), complemento([to, current, therapies])]). relacion([sujeto(['We']), verbo([have]), complemento([demonstrated, a, critical, role, for, 'PARP', in, experimental, asthma])]). relacion([sujeto(['Administration', of, olaparib, in, mice, 30, min, 'post-challenge']), verbo([promoted]), complemento([a, robust, reduction, in, airway, 'eosinophilia,', mucus, production, and, hyperresponsiveness, even, after, repeated, challenges, with, ovalbumin])]). relacion([sujeto(['The', protective, effects, of, olaparib, were, linked, to, a, suppression, of, 'Th2', cytokines, 'eotaxin,', 'IL-4,', 'IL-5,', 'IL-6,', 'IL-13,', and, 'M-CSF,', and, 'ovalbumin-specific', 'IgE', with, an]), verbo([increase]), complemento([in, the, 'Th1', cytokine, 'IFN-γ'])]). relacion([sujeto(['These', traits, were]), verbo([associated]), complemento([with, a, decrease, in, splenic, 'CD4(+)', 'T', cells, and, concomitant, increase, in, 'T-regulatory', cells])]). relacion([sujeto(['The', aforementioned, traits]), verbo([conferred]), complemento([by, olaparib, administration, were, consistent, with, those, observed, in, 'OVA-challenged', 'PARP-1(-/-)', mice])]). relacion([sujeto(['Adoptive', transfer, of, 'Th2-skewed', 'OT-II-WT', 'CD4(+)', 'T', cells, reversed, the, 'Th2', cytokines, 'IL-4,', 'IL-5,', and, 'IL-10,', the, chemokine, 'GM-CSF,', the, 'Th1', cytokines, 'IL-2', and, 'IFN-γ,', and, 'ovalbumin-specific', 'IgE', production, in, 'ovalbumin-challenged', 'PARP-1(-/-)mice']), verbo([suggesting]), complemento([a, role, for, 'PARP-1', in, 'CD4(+)', 'T', but, not, 'B', cells])]). relacion([sujeto(['In', ex, vivo, 'studies,', 'PARP', inhibition, by, olaparib, or, 'PARP-1', gene, knockout, markedly, reduced, 'CD3/CD28-stimulated', 'gata-3', and, il4, expression, in, 'Th2-skewed', 'CD4(+)', 'T', cells, while]), verbo([causing]), complemento([a, moderate, elevation, in, 't-bet', and, 'ifn-γ', expression, in, 'Th1-skewed', 'CD4(+)', 'T', cells])]). relacion([sujeto(['Prognostic', markers, for, late, events]), verbo([have]), complemento([been, more, elusive])]). relacion([sujeto(['TFAP2C', '(', 'AP2γ)']), verbo([regulates]), complemento([the, expression, of, 'ERα,', the, 'ERα', pioneer, factors, 'FOXA1', and, 'GATA3,', and, controls, 'ERα-dependent', transcription])]). relacion([sujeto(['TFPAC2', overexpression, did, not, impact, overall, survival, during, the, first, 10, years, after, 'diagnosis,', but, was]), verbo([associated]), complemento([with, a, shorter, survival, after, 10, years, '(', 'HR', 3.4, ',', 95, '%', 'CI', 1.58, ',', 7.3, ;, p, value, =, 0.002, ')'])]). relacion([sujeto(['However,', although, the, morphological, changes, during, larval, shell, formation]), verbo([have]), complemento([been, well, 'described,', the, underlying, molecular, mechanisms, remain, poorly, understood])]). relacion([sujeto(['In', this, 'study,', we, focused, on, the, potential, involvement, of, a, 'GATA', gene, in, shell, formation, because, 'GATA', genes, are, often, downstream, genes, of, 'BMP', '(', bone, morphogenetic, 'protein)', signaling, 'pathways,', which]), verbo([have]), complemento([been, suggested, to, participate, in, molluscan, shell, formation])]). relacion([sujeto(['This', expression, pattern, supports, the, notion, that, 'cgi-gata2/3', gene, plays]), verbo([conserved]), complemento([roles, in, bilaterian, ectodermal, development])]). relacion([sujeto(['The', expression, of, 'cgi-gata2/3', away, from, the, shell, field, may, be]), verbo([involved]), complemento([in, hematopoiesis])]). relacion([sujeto(['Our', results]), verbo([provide]), complemento([fundamental, support, for, studies, into, the, molecular, mechanisms, of, larval, shell, formation, and, the, functions, of, molluscan, 'GATA', genes])]). relacion([sujeto(['The', pathogenesis, of, encapsulating, peritoneal, sclerosis]), verbo([has]), complemento([not, been, 'elucidated,', but, several, putative, factors, necessary, for, the, development, of, peritoneum, fibrosis, '(', 'PF)', have, been, reported])]). relacion([sujeto(['Cytokines', analysis, in, peritoneal, fluid, showed, that, 'IFN-γ', was, significantly]), verbo([increased]), complemento([in, 'CG-injected', 'T-bet', 'Tg', mice, and, that, 'IL-13', was, significantly, increased, in, 'CG-injected', 'GATA-3', 'Tg', mice])]). relacion([sujeto(['Our', results]), verbo([suggest]), complemento([that, 'Th2', cells, may, play, roles, in, the, development, of, experimental, 'PF', and, that, 'Th1', cells, may, alleviate, the, severity, of, experimental, 'PF'])]). relacion([sujeto(['Recent', studies]), verbo([have]), complemento([suggested, that, 'GATA3', is, a, sensitive, and, relatively, specific, biomarker, for, urothelial, and, breast, 'carcinomas,', with, most, 'Müllerian', carcinomas, being, negative])]). relacion([sujeto(['GATA3']), verbo([nuclear]), complemento([intensity, and, extent, of, staining, was, evaluated])]). relacion([sujeto(['Although', atrial, natriuretic, peptide, '(', 'ANP)']), verbo([has]), complemento([been, well, recognized, for, its, role, in, the, regulation, of, 'volume-pressure', homeostasis, in, cardiovascular, 'system,', its, impact, on, respiratory, 'system,', particularly, on, the, pathogenesis, of, acute, allergic, 'asthma,', is, yet, to, be, elucidated])]). relacion([sujeto(['In', the, present, 'report,', we]), verbo([induced]), complemento([mice, with, 'OVA', for, onset, of, acute, allergic, asthma, along, with, the, administration, of, recombinant, 'ANP', or, 'A71915', '(', an, antagonist, for, 'ANP/natriuretic', peptide, receptor, 'A,', 'NPRA)'])]). relacion([sujeto(['It', was, noted, that, treatment, of, mice, with, 'ANP', significantly]), verbo([promoted]), complemento([inflammatory, infiltration, in, the, airway, and, the, production, of, inflammatory, cytokines, in, the, bronchoalveolar, lavage, fluid, '(', 'BALF)', and, lung, 'homogenates,', and, the, number, of, inflammatory, cells, in, the, 'BALF', was, significantly, higher, as, compared, with, that, of, 'PBS', treated, asthmatic, mice])]). relacion([sujeto(['Mechanistic', studies, revealed, that, 'ANP', repressed, the, expression, of, 'Th1', transcription, factor, 'T-bet,', but]), verbo([enhanced]), complemento(['Th2', transcription, 'GATA3', expression])]). relacion([sujeto(['Together,', our, data]), verbo([provided]), complemento([feasible, evidence, suggesting, that, 'ANP/NPRA', signaling, predominantly, induces, a, 'Th2-type', response, in, favor, of, pathological, processes, during, the, course, of, acute, allergic, asthma])]). relacion([sujeto(['Cytokines', from, group, 2, innate, lymphoid, cells, '(', 'ILC2s)']), verbo([have]), complemento([been, implicated, in, acute, allergic, 'responses,', such, as, 'papain-induced', lung, inflammation])]). relacion([sujeto(['However,', the, means, of, homeostatic, regulation, of, 'ILC2s']), verbo([have]), complemento([not, been, established])]). relacion([sujeto(['Intranasal', administration, of, papain]), verbo([stimulated]), complemento(['IL-5', and, 'IL-13', production, in, the, 'lung,', which, was, enhanced, when, 'Spred1', was, deleted])]). relacion([sujeto(['On', the, 'contrary,', a, 'MEK', inhibitor]), verbo([suppressed]), complemento(['ILC2', proliferation, and, cytokine, production])]). relacion([sujeto(['Spred1', deficiency, resulted, in, stabilization, of, 'GATA3,', which]), verbo([has]), complemento([been, shown, to, play, essential, roles, in, the, maintenance, and, cytokine, production, of, 'ILC2'])]). relacion([sujeto(['These', data]), verbo([suggest]), complemento([that, 'Spred1', negatively, regulates, 'ILC2', development, and, functions, through, the, suppression, of, the, 'Ras-ERK', pathway])]). relacion([sujeto(['A', better, understanding, of, the, mechanism, and, manipulation, of, the, tightly]), verbo([regulated]), complemento([cellular, differentiation, process, of, adipogenesis, may, contribute, to, a, reduction, in, obesity, and, diabetes])]). relacion([sujeto(['Multiple', transcription, factors, and, signaling, pathways, are]), verbo([involved]), complemento([in, the, regulation, of, adipogenesis])]). relacion([sujeto(['Here,', we]), verbo([report]), complemento([that, the, 'AMP-activated', protein, kinase, 'activator,', 5, -, 'aminoimidazole-4-carboxamide', ribonucleoside, '(', 'AICAR)', can, activate, 'AMPK', in, preadipocytes, and, thus, increase, the, expression, of, 'GATA3,', an, 'anti-adipogenic', factor])]). relacion([sujeto(['However,', 'AICAR-increased', 'GATA3', is]), verbo([mediated]), complemento([by, the, stimulation, of, 'Wnt/β-catenin', signaling, in, preadipocytes])]). relacion([sujeto(['Mechanistically,', 'AICAR-activated', 'AMPK']), verbo([inhibits]), complemento(['GSK3β', through, a, phosphorylation, process, that, stabilizes, 'β-catenin'])]). relacion([sujeto(['This', stabilized, 'β-catenin', then, translocates, into, nucleus, where, it]), verbo([interacts]), complemento([with, 'T-cell', factors, '(', 'TCF),', leading, to, the, increased, 'β-catenin/TCF', transcriptional, activity, that, induces, 'GATA3', expression])]). relacion([sujeto(['Furthermore,', 'GATA3']), verbo([suppresses]), complemento([key, adipogenic, regulators, by, binding, to, the, promoters, of, these, 'regulators,', such, as, the, peroxisome, 'proliferator-activated', 'receptor-γ', '(', 'PPARγ)', 'gene,', and, the, disruption, of, 'Wnt/β-catenin', signaling, reduces, the, 'GATA3', binding, at, the, 'PPARγ', promoter])]). relacion([sujeto(['In', differentiated, 'adipocytes,', 'GATA3', expression, inhibition, is, facilitated, by, the, 'down-regulation', of, 'β-catenin', 'levels,', the, reduction, in, 'β-catenin', 'binding,', and, the]), verbo([increase]), complemento([in, 'CtBP', binding, at, the, 'GATA3', promoter])]). relacion([sujeto(['Our', findings, shed, light, on, the, molecular, mechanism, of, adipogenesis, by]), verbo([suggesting]), complemento([that, different, regulation, pathways, and, adipogenic, regulators, collectively, modulate, adipocyte, differentiation, through, 'cross-talk'])]). relacion([sujeto(['WNT/β-catenin', signaling]), verbo([has]), complemento([been, described, as, a, crucial, regulator, of, embryonic, stem, cells, and, embryogenesis])]). relacion([sujeto(['β-Catenin', was, displayed, in, the, cortical, region, underneath, the, membrane, during, all, 'stages,', but, it, only, showed]), verbo([nuclear]), complemento([localization, at, cleavage, stages, after, stabilization, with, 1, -, 'Azakenpaullone'])]). relacion([sujeto(['However,', both, 'β-catenin', degradation, and, stabilization]), verbo([caused]), complemento([inhibition, of, the, trophectoderm, '(', 'TE)', 'fate,', illustrated, by, 'KRT18', and, 'GATA3', 'RNA,', and, 'CDX2', protein, expression])]). relacion([sujeto(['The', addition, of, either, 'WNT3', or, 1, -, 'Azakenpaullone', to, the, culture, medium]), verbo([promoted]), complemento(['EOMES', expression, specific, for, trophoblast, development])]). relacion([sujeto(['In', both, 'studies,', the, canonical, 'WNT', pathway]), verbo([target]), complemento(['gene,', 'TCF1,', was, not, affected])]). relacion([sujeto(['Therefore,', we, conclude, that, 'WNT3', and, 'membrane-associated', 'β-catenin']), verbo([promote]), complemento([progenitor, trophoblast, development, in, human, blastocysts])]). relacion([sujeto(['These', results]), verbo([have]), complemento([important, implications, in, assisted, reproduction, and, stem, cell, biology])]). relacion([sujeto(['While', genomics, data]), verbo([have]), complemento([been, heavily, 'used,', protein, signaling, data, are, more, directly, connected, to, biological, phenotype, and, might, predict, cancer, phenotypes, such, as, 'invasion,', 'metastasis,', and, patient, survival])]). relacion([sujeto(['In', this, 'study,', we, mined, publicly, available, data, for, colorectal, adenocarcinoma, from, the, 'Cancer', 'Genome', 'Atlas', and, identified, protein, expression, and, signaling, changes, that, are, statistically]), verbo([associated]), complemento([with, patient, outcome])]). relacion([sujeto(['High', levels, of, insulin, growth, factor]), verbo([binding]), complemento([protein, 2, '(', 'IGFBP2)', were, associated, with, both, recurrence, and, 'death,', and, this, was, validated, by, immunohistochemical, staining, of, a, tissue, microarray, for, a, secondary, patient, dataset])]). relacion([sujeto(['Interestingly,', 'GATA']), verbo([binding]), complemento([protein, 3, '(', 'GATA3)', was, the, protein, most, frequently, associated, with, death, in, our, 'analysis,', and, 'GATA3', expression, was, significantly, decreased, in, tumor, samples, from, stage, 'I-II', deceased, patients])]). relacion([sujeto(['Experimental', studies, using, engineered, colon, cancer, cell, lines, show, that, exogenous, expression, of, 'GATA3']), verbo([decreases]), complemento(['three-dimensional', colony, growth, and, invasiveness, of, colon, cancer, cells, but, does, not, affect, 'two-dimensional', proliferation])]). relacion([sujeto(['These', findings]), verbo([suggest]), complemento([that, protein, data, are, useful, for, biomarker, discovery, and, identify, 'GATA3', as, a, regulator, of, colorectal, 'cancer ', aggressiveness])]). relacion([sujeto(['Paracoccidioidomycosis', '(', 'PCM),']), verbo([caused]), complemento([by, 'Paracoccidioides', species, is, a, prevalent, systemic, and, progressive, mycosis, that, occurs, in, 'Latin', 'America'])]). relacion([sujeto(['It', is]), verbo([caused]), complemento([by, 'Paracoccidioides', species])]). relacion([sujeto([brasiliensis, '(', 'gp43)']), verbo([confers]), complemento([protection, in, experimental, 'PCM'])]). relacion([sujeto(['DCs', link, innate, and, adaptive, immunity, by]), verbo([recognizing]), complemento([invading, pathogens, and, selecting, the, type, of, effector, 'T', cell, to, mediate, the, immune, response])]). relacion([sujeto(['Here,', we, showed, that, 'DC-pMAC/PS-scFv']), verbo([induces]), complemento([the, activation, of, 'CD4+', and, 'CD8+', 'T', cells])]). relacion([sujeto(['Analysis', of, regional, lymph, nodes, revealed]), verbo([increases]), complemento([in, the, expression, of, 'clec7a,', 'myd88,', 'tlr2,', gata3, and, 'tbx21,', which, are, involved, in, the, immune, response])]). relacion([sujeto(['Taken', 'together,', our, results, indicate, that, the, scFv]), verbo([modulates]), complemento([the, humoral, and, cellular, immune, responses, and, presents, epitopes, to, 'CD4+', and, 'CD8+', 'T', cells])]). relacion([sujeto(['Tfap2c', is]), verbo([required]), complemento([for, placental, development, and, trophoblast, stem, cell, maintenance])]). relacion([sujeto(['Deletion', of, 'Tfap2c', results, in, early, embryonic]), verbo([loss]), complemento([because, of, failure, in, placental, development])]). relacion([sujeto(['Labyrinthine', differentiation, was, 'impaired,', as, indicated, by]), verbo([enhanced]), complemento([proliferation, and, inclusions, of, 'cobblestone-shaped', cell, clusters, characterized, by, expression, of, 'Tfap2c', and, glycogen, stores])]). relacion([sujeto(['Moreover,', expression, of, marker, genes, such, as, 'Cdx2,', 'Eomes,', 'Gata3,', and, 'Ascl2', are]), verbo([decreased]), complemento([in, the, spongiotrophoblast, and, indicate, a, lowered, stem, cell, potential])]). relacion([sujeto(['On', 'Day', 18.5, 'postcoitum,', the, labyrinth, layer, of, 'Tfap2c(+/-)', placentas, exhibited, massive, hemorrhages, in, the, maternal, blood, 'spaces;', these, hemorrhages, might]), verbo([have]), complemento([contributed, to, the, significantly, reduced, number, of, 'live-born', pups])]). relacion([sujeto(['These', morphological, alterations, were, accompanied, by, a, shift, toward, sinusoidal, trophoblast, giant, cells, as, the, cell, subpopulation, lining, the, maternal, sinusoids, and, toward, reduction, in, expression, of, the, prolactin, gene, family, member, 'Prl2c2,', a]), verbo([finding]), complemento([characteristic, of, the, spiral, arteries, lining, trophoblast, cells])]). relacion([sujeto(['Taken', 'together,', these, findings, indicate, that, a, reduction, in, the, gene, dosage, of, placental, 'Tfap2c']), verbo([leads]), complemento([to, morphological, changes, in, the, labyrinth, at, midgestation, and, in, the, maternal, blood, spaces, during, late, pregnancy])]). relacion([sujeto(['The', expressions, of, 'GATA']), verbo([binding]), complemento([protein, 3, '(', 'GATA3),', interleukin, 4, '(', 'IL-4),', 'T-box', expressed, in, 'T', cells, '(', 'T-bet),', 'interferon-γ', '(', 'IFN-γ)', and, 'Foxp3', mRNAs, in, mouse, splenic, cells, were, detected, by, 'real-time', quantitative, 'PCR', '(', 'qRT-PCR),', and, the, percentage, of, 'GATA3+', or, 'Foxp3+', cells, in, lymphocytes, of, mouse, spleen, was, detected, by, flow, cytometry])]). relacion([sujeto(['The', expressions, of, 'GATA3,', 'Th1', specific, markers, 'T-bet', and, 'IFN-γ,', and, regulatory, 'T', cell, '(', 'Treg)', specific, marker, 'Foxp3', mRNAs, in, mouse, spleen, 'cells,', but, no, significant, change, was]), verbo([found]), complemento([in, 'IL-4', mRNA, expression])]). relacion([sujeto([β2GPI, immunization, could]), verbo([induce]), complemento(['Th2', cell, bias, polarization, and, 'Th1', cell, and, 'Treg', suppression, in, 'mice,', which, might, contribute, to, the, production, of, aβ2GPI, 'Ab'])]). relacion([sujeto(['In', this, 'review,', 'I', will, focus, on, the, signaling, pathways, and, key, molecules, that, determine, the, differentiation, of, naïve, 'CD4', 'T', cells, into, 'Th2', 'cells,', and, how, the, expression, of, 'Th2', 'cytokines,', especially, 'IL-4', and, 'IL-13,', is]), verbo([regulated]), complemento([in, 'Th2', cells])]). relacion([sujeto(['Here,', we]), verbo([report]), complemento([that, 'GATA3', nucleates, a, transcription, repression, program, composed, of, 'G9A', and, 'MTA3-,', but, not, 'MTA1-', or, 'MTA2-,', constituted, 'NuRD', complex])]). relacion([sujeto(['Genome-wide', analysis, of, the, 'GATA3/G9A/NuRD(MTA3)']), verbo([targets]), complemento([identified, a, cohort, of, genes, including, 'ZEB2', that, are, critically, involved, in, 'epithelial-to-mesenchymal', transition, and, cell, invasion])]). relacion([sujeto(['We', demonstrate, that, the, 'GATA3/G9A/NuRD(MTA3)', complex]), verbo([inhibits]), complemento([the, invasive, potential, of, breast, cancer, cells, in, vitro, and, suppresses, breast, cancer, metastasis, in, vivo])]). relacion([sujeto(['Strikingly,', the, expression, of, 'GATA3,', 'G9A,', and, 'MTA3', is, concurrently, downregulated, during, breast, cancer, 'progression,']), verbo([leading]), complemento([to, an, elevated, expression, of, 'ZEB2,', 'which,', in, 'turn,', represses, the, expression, of, 'G9A', and, 'MTA3', through, the, recruitment, of, 'G9A/NuRD(MTA1)'])]). relacion([sujeto(['IFN-α/β', was, first, described, as, a, potent, inhibitor, of, viral, 'replication,', but, it, is, now, appreciated, that, 'IFN', signaling, plays, a, pleiotropic, role, in]), verbo([regulating]), complemento([peripheral, 'T', cell, functions])]). relacion([sujeto(['Recently,', 'IFN-α/β', was, shown, to, block, human, 'Th2', development, by]), verbo([suppressing]), complemento([the, transcription, factor, 'GATA3'])]). relacion([sujeto(['This', effect, is, consistent, with, the, role, for, 'IFN-α/β', in]), verbo([suppressing]), complemento([allergic, inflammatory, processes, by, blocking, granulocyte, activation, and, 'IL-4-mediated', 'B', cell, isotype, switching, to, 'IgE'])]). relacion([sujeto(['Is', it, possible, to, overcome, these, events, by, treating, with, 'IFN-α/β', or, by]), verbo([inducing]), complemento([its, secretion, in, 'vivo?', 'In', support, of, this, 'approach,', case, studies, have, documented, the, therapeutic, potential, of, 'IFN-α/β', in, treating, 'steroid-resistant', allergic, asthma, and, other, atopic, diseases])]). relacion([sujeto(['Additionally,', individuals, with, asthma, who, are, infected, with, 'HCV', and]), verbo([respond]), complemento([to, 'IFN', therapy, showed, a, reduction, in, symptoms, and, severity, of, asthma, attacks])]). relacion([sujeto(['These', findings, support, a, 'model,', whereby, allergic, and, antiviral, responses, are, able, to, 'cross-regulate', each, 'other,', as, 'IgER', 'cross-linking', of, pDCs]), verbo([prevents]), complemento(['IFN-α/β', production, in, response, to, viral, infection])]). relacion([sujeto(['Blood', 'T', cell, progenitors]), verbo([have]), complemento([been, 'detected,', but, their, source, in, the, bone, marrow, '(', 'BM)', remains, unclear])]). relacion([sujeto(['Second,', although, 'Flt3(-)', 'CLPs', are, less, common, in, the, 'BM,', they, are, abundant, in, the, blood, and]), verbo([have]), complemento([reduced, 'Cd25(+)-expressing', cells, and, downregulated, 'c-Kit', and, 'IL-7Rα', intensities])]). relacion([sujeto(['Third,', in, 'contrast,', stage, 3, 'MPP', '(', 'MPP3)', 'cells,', the, unique, circulating, 'MPP', 'subset,']), verbo([have]), complemento([upregulated, 'Il7r,', 'Gata3,', and, 'Notch1', in, comparison, with, 'BM-resident', counterparts])]). relacion([sujeto(['Although', several, lymphoid, genes, are]), verbo([expressed]), complemento([by, 'MPP3', cells, and, 'Flt3(-)', 'CLPs,', the, latter, only, give, rise, to, 'B', cells, in, the, 'spleen,', and, 'Notch1', expression, level, is, not, modulated, in, the, 'blood,', as, for, 'MPP3', cells])]). relacion([sujeto(['We', conclude, that, 'CLPs']), verbo([have]), complemento([reached, the, point, where, they, cannot, be, a, 'Notch1', 'target,', a, limiting, condition, on, the, path, to, 'T', cell, engagement])]). relacion([sujeto(['Recent', work, indicates, that, the]), verbo([nuclear]), complemento([envelope, is, a, major, signaling, node, for, the, cell, that, can, influence, tissue, differentiation, processes])]). relacion([sujeto(['Here', we, present, two]), verbo([nuclear]), complemento([envelope, 'trans-membrane', proteins, 'TMEM120A', and, 'TMEM120B', that, are, paralogs, encoded, by, the, 'Tmem120A', and, 'Tmem120B', genes])]). relacion([sujeto(['The', 'TMEM120', proteins, are]), verbo([expressed]), complemento([preferentially, in, fat, and, both, are, induced, during, 3, 'T3-L1', adipocyte, differentiation])]). relacion([sujeto(['Knockdown', of, one, or, the, other, protein, altered, expression, of, several, genes]), verbo([required]), complemento([for, adipocyte, 'differentiation,', 'Gata3,', 'Fasn,', 'Glut4,', while, knockdown, of, both, together, additionally, affected, 'Pparg', and, 'Adipoq'])]). relacion([sujeto(['The', double, knockdown, also]), verbo([increased]), complemento([the, strength, of, 'effects,', reducing, for, example, 'Glut4', levels, by, 95, '%', compared, to, control, 3, 'T3-L1', cells, upon, pharmacologically, induced, differentiation])]). relacion([sujeto(['Accordingly,', 'TMEM120A', and, 'B', knockdown, individually, and, together, impacted, on, adipocyte, 'differentiation/metabolism', as, measured, by, lipid, accumulation, through]), verbo([binding]), complemento([of, 'Oil', 'Red', 'O', and, coherent, 'anti-Stokes', 'Raman', scattering, microscopy, '(', 'CARS)'])]). relacion([sujeto(['The']), verbo([nuclear]), complemento([envelope, is, linked, to, several, lipodystrophies, through, mutations, in, lamin, 'A;', 'however,', lamin, 'A', is, widely, expressed])]). relacion([sujeto(['Thus', it, is, possible, that, the, 'TMEM120A', and, 'B', 'fat-specific']), verbo([nuclear]), complemento([envelope, transmembrane, proteins, may, play, a, contributory, role, in, the, 'tissue-specific', pathology, of, this, disorder, or, in, the, wider, problem, of, obesity])]). relacion([sujeto(['Cytokine', 'IL-17', family, consists, of, 6, 'members;', 'IL-17A', to, 'IL-17F,', among, which, 'IL-25']), verbo([has]), complemento([a, unique, structure, and, function])]). relacion([sujeto(['The', receptor, of, 'IL-25', '(', 'IL-17BR)', is, highly]), verbo([expressed]), complemento([in, the, main, 'Th2', cells])]). relacion([sujeto(['IL-25']), verbo([regulates]), complemento([the, internal, safety, of, adaptive, immune, responses, which, leads, to, begin, allergic, diseases, and, plays, a, role, in, stimulation, of, pulmonary, mucosal, cells, and, fibroblasts])]). relacion([sujeto(['IL-25', can, also]), verbo([have]), complemento([some, effects, on, production, of, other, cytokines])]). relacion([sujeto(['For', 'instance,', production, of, 'IL-25', in, human, and, mice, or, injection, of, 'IL-25', to, animals]), verbo([has]), complemento([resulted, in, production, of, high, concentrations, of, 'Th2', 'cytokines,', including, 'IL-4,', 'IL-5,', and, 'IL-13'])]). relacion([sujeto(['Pilot', studies]), verbo([have]), complemento([shown, that, mRNA, of, 'IL-25', has, a, high, expression, in, 'Th2', cells])]). relacion([sujeto(['However,', the, mechanism, through, which, 'IL-25']), verbo([leads]), complemento([to, 'Th2', immune, response, is, still, unknown])]). relacion([sujeto(['Reaction', between, 'IL-25', and, 'IL-17BR']), verbo([leads]), complemento([to, activation, of, transcription, 'factors,', such, as, 'NF-KB,', 'STAT6,', 'GATA3,', 'NF-ATC1,', 'JUNNB,', 'MAPK,', and, 'JNK'])]). relacion([sujeto(['IL-25']), verbo([has]), complemento([been, used, against, the, kidney, damage, in, mice])]). relacion([sujeto([and, 'Taiwan,']), verbo([have]), complemento([stated, that, 'IL-25', is, a, strong, inflammatory, cytokine, protein, which, is, involved, in, allergic, inflammations])]). relacion([sujeto(['Molecular', stratification, of, bladder, cancer]), verbo([has]), complemento([revealed, gene, signatures, differentially, expressed, across, tumor, subtypes])]). relacion([sujeto(['While', these, signatures]), verbo([provide]), complemento([important, insights, into, subtype, 'biology,', the, transcriptional, regulation, that, governs, these, signatures, is, not, well, characterized])]). relacion([sujeto(['In', this, 'study,', we, use, publically, available, 'ChIP-Seq', data, on, regulatory, factor]), verbo([binding]), complemento([in, order, to, link, transcription, factors, to, gene, signatures, defining, molecular, subtypes, of, urothelial, carcinoma])]). relacion([sujeto(['We', link, the, 'PLK1-FOXM1', axis, to, the, rapidly, proliferating, 'Genomically', 'Unstable', and, 'SCC-like', subtypes, and, show, that, differentiation, programs]), verbo([involving]), complemento(['PPARG/RXRA,', 'FOXA1/GATA3', and, 'HOXA/HOXB', are, differentially, expressed, in, 'UC', molecular, subtypes])]). relacion([sujeto(['We', show, that, gene, signatures, and, regulatory, systems, defined, in, urothelial, carcinoma, operate, in, breast, cancer, in, a, subtype, specific, 'manner,']), verbo([suggesting]), complemento([similarities, at, the, gene, regulatory, level, of, these, two, tumor, types])]). relacion([sujeto(['Urobasal', tumors]), verbo([maintain]), complemento([an, apparent, urothelial, differentiation, axis, composed, of, 'PPARG/RXRA,', 'FOXA1/GATA3', and, anterior, 'HOXA', and, 'HOXB', genes])]). relacion([sujeto(['Genomically', 'Unstable', and, 'SCC-like', tumors, differ, from, 'Urobasal', tumors, by, a, strong]), verbo([increase]), complemento([of, proliferative, activity, through, the, 'PLK1-FOXM1', axis, operating, in, both, subtypes])]). relacion([sujeto(['Recent', studies, indicate, that, 'DNA', methylation, can, be, used, to, identify, transcriptional, 'enhancers,', but, no, systematic, approach]), verbo([has]), complemento([been, developed, for, 'genome-wide', identification, and, analysis, of, enhancers, based, on, 'DNA', methylation])]). relacion([sujeto(['We', identified, networks]), verbo([regulated]), complemento([by, known, cancer, drivers, such, as, 'GATA3', and, 'FOXA1', '(', breast, 'cancer),', 'SOX17', and, 'FOXA2', '(', endometrial, 'cancer),', and, 'NFE2L2,', 'SOX2,', and, 'TP63', '(', squamous, cell, lung, 'cancer)'])]). relacion([sujeto(['We', propose, 'ELMER', as, a, powerful, new, paradigm, for, understanding, the, 'cis-regulatory', interface, between, 'cancer-associated', transcription, factors, and, their, functional]), verbo([target]), complemento([genes])]). relacion([sujeto(['Therapeutic']), verbo([targeting]), complemento([of, 'GATA3,', an, important, transcription, factor, of, the, 'Th2', 'pathway,', may, be, beneficial])]). relacion([sujeto(['We', conducted, a, 'randomized,', 'double-blind,', 'placebo-controlled,', multicenter, clinical, trial, of, 'SB010']), verbo([involving]), complemento([patients, who, had, allergic, asthma, with, sputum, eosinophilia, and, who, also, had, biphasic, early, and, late, asthmatic, responses, after, 'laboratory-based', allergen, provocation])]). relacion([sujeto(['After', 28, 'days,', 'SB010', attenuated, the, mean, late, asthmatic, response, by, 34, '%', ',', as, compared, with, the, baseline, 'response,', according, to, the, 'AUC', for, 'FEV1,', whereas, placebo, was]), verbo([associated]), complemento([with, a, 1, '%', increase, in, the, 'AUC', for, 'FEV1', '(', 'P=0'])]). relacion([sujeto(['The', early, asthmatic, response, with, 'SB010', was, attenuated, by, 11, '%', as, measured, by, the, 'AUC', for, 'FEV1,', whereas, the, early, response, with, placebo, was]), verbo([increased]), complemento([by, 10, '%', '(', 'P=0'])]). relacion([sujeto(['Inhibition', of, the, late, asthmatic, response, by, 'SB010', was]), verbo([associated]), complemento([with, attenuation, of, 'allergen-induced', sputum, eosinophilia, and, with, lower, levels, of, tryptase, in, sputum, and, lower, plasma, levels, of, 'interleukin-5'])]). relacion([sujeto(['In', this, 'study,', we]), verbo([found]), complemento([the, markedly, elevated, levels, of, the, 'ILC1', transcription, factor, 'T-bet,', the, effector, cytokine, 'IFN-γ', and, the, 'IL/receptor', signaling, molecules, 'IL-12/IL-12R,', which, are, indispensable, for, 'ILC1', 'differentiation,', in, the, helper, 'ILCs', of, chronic, hepatitis, 'B', '(', 'CHB)', patients])]). relacion([sujeto(['The', elevated, level, of, the, 'ILC1', population, was, significantly]), verbo([associated]), complemento([with, hepatic, damage, in, 'CHB', 'patients,', and, was, not, related, to, telbivudine, treatment])]). relacion([sujeto(['The', findings, of, this, study]), verbo([suggest]), complemento([potential, 'pro-inflammatory', roles, for, 'ILC1s', in, 'CHB', 'pathogenesis,', potentiating, these, cells, and, their, related, molecules, as, targets, of, 'diagnostic,', prognostic, 'and/or', therapeutic, strategies, for, hepatitis, 'B'])]). relacion([sujeto(['Paeoniflorin']), verbo([has]), complemento([been, demonstrated, to, exert, 'anti-inflammatory', and, immunomodulatory, effects, in, the, animal, study])]). relacion([sujeto(['Our', study, demonstrated, 'that,', compared, with, model, 'group,', paeoniflorin]), verbo([inhibited]), complemento([ovalbumin, '(', 'OVA)-induced', increases, in, 'Raw', and, eosinophil, 'count;', interleukin, '(', 'IL)-4,', 'IgE', levels, were, recovered, in, bronchoalveolar, lavage, fluid, 'compared;', increased, 'IFN-γ', level, in, bronchoalveolar, lavage, 'fluid;', histological, studies, demonstrated, that, paeoniflorin, substantially, inhibited, 'OVA-induced', eosinophilia, in, lung, tissue, and, lung, tissue, compared, with, model, group])]). relacion([sujeto(['Flow', cytometry, studies, demonstrated, that, paeoniflorin, can]), verbo([regulate]), complemento(['Th1/Th2', balance])]). relacion([sujeto(['These', findings]), verbo([suggest]), complemento([that, paeoniflorin, may, effectively, ameliorate, the, progression, of, asthma, and, could, be, used, as, a, therapy, for, patients, with, allergic, asthma])]). relacion([sujeto(['Rhodiola', rosea, '(', 'Rro)']), verbo([has]), complemento([been, reported, to, have, various, pharmacological, 'properties,', including, 'anti-fatigue,', 'anti-stress', and, 'anti-inflammatory', activity])]). relacion([sujeto(['The', 'RS', extract, significantly]), verbo([induced]), complemento([higher, apoptosis, and, lipolysis, in, comparison, to, control, cells, and, to, 'RR', extract])]). relacion([sujeto(['Differentiation', of, 'pre-adipocytes', in, the, presence, of, 'RS', and, 'RR', extracts, showed, a, significant]), verbo([decrease]), complemento([in, expression, of, genes, involved, in, adipocyte, function, such, as, 'SLC2A4', and, the, adipogenic, factor, 'FGF2', and, significant, increase, in, expression, of, genes, involved, in, inhibition, of, 'adipogenesis,', such, as, 'GATA3,', 'WNT3A,', 'WNT10B'])]). relacion([sujeto(['Liposome-protamine-DNA', nanoparticles, '(', 'LPD)', are, 'safe,', 'effective,', and, 'non-toxic', adjuvants, that]), verbo([induce]), complemento(['Th1-like', immune, responses])]). relacion([sujeto(['Treatment', with, the, 'LPD-rHM', resulted, in, a, reduction, in, 'IgE', and, a, marked]), verbo([increase]), complemento([in, 'IgG2a'])]). relacion([sujeto(['The', 'LPD-rHM']), verbo([induced]), complemento(['allergen-specific', responses, with, relatively, high, 'interferon-gamma', 'production,', as, well, as, expression, of, the, transcription, factor, 'T-bet', in, stimulated, splenocytes])]). relacion([sujeto(['Removal', of, the, nanoparticles, from, the, rHM, resulted, in, a]), verbo([decrease]), complemento([in, the, 'allergen\'s', immunogenicity])]). relacion([sujeto(['These', results, indicate, that, the, rHM, complexed, with, 'LPD', nanoparticles]), verbo([has]), complemento([a, marked, suppressive, effect, on, the, allergic, response, and, caused, a, shift, toward, a, 'Th1', pathway])]). relacion([sujeto(['The', prosomeric, model, by, 'Puelles', and, 'Rubenstein', '(', 1993, ')']), verbo([suggests]), complemento([that, the, alar, plate, of, the, posterior, diencephalon, is, partitioned, into, three, different, prosomeres, '(', designated, 'p1-p3),', which, develop, into, the, 'pretectum,', 'thalamus,', and, 'prethalamus,', respectively])]). relacion([sujeto(['Here,', we]), verbo([report]), complemento([the, developmental, consequences, of, genetic, ablation, of, cell, populations, from, the, diencephalic, basal, plate])]). relacion([sujeto(['The', strategy, for, conditionally]), verbo([regulated]), complemento([cell, ablation, is, based, on, the, targeted, expression, of, the, diphtheria, toxin, gene, '(', 'DTA)', to, the, diencephalic, basal, plate, via, 'tamoxifen-', 'induced,', 'Cre-mediated', recombination, of, the, 'ROSA(DTA)', allele])]). relacion([sujeto(['We', show, that, activation, of, 'DTA']), verbo([leads]), complemento([to, specific, cell, loss, in, the, basal, plate, of, the, posterior, 'diencephalon,', and, disrupted, early, regionalization, of, distinct, alar, territories])]). relacion([sujeto(['We', also, show, that, these, defects]), verbo([lead]), complemento([to, abnormal, nuclear, organization, at, later, developmental, stages])]). relacion([sujeto(['Our', data]), verbo([have]), complemento([implications, for, increased, understanding, of, the, interactive, roles, between, discrete, diencephalic, compartments])]). relacion([sujeto(['We', sought, to]), verbo([find]), complemento([susceptibility, loci, by, performing, the, first, 'genome-wide', association, study, '(', 'GWAS)', of, 'AD', in, 'Korean', children, with, recalcitrant, 'AD,', which, was, defined, as, 'moderate-to-severe', 'AD', with, allergic, sensitization])]). relacion([sujeto([31, were]), verbo([associated]), complemento([with, recalcitrant, 'AD', at, a, 'genome-wide', threshold, of, significance, '(', 'P <', 2.0, ×, 10, '(', -, 8, ')', ')'])]). relacion([sujeto(['These']), verbo([associated]), complemento(['SNPs', are, more, than, 1, 'Mb', from, the, closest, 'gene,', protocadherin, '(', 'PCDH)9'])]). relacion([sujeto([3, ')', ',', 'thymus-expressed', molecule]), verbo([involved]), complemento([in, selection, '(', 'THEMIS;', 6, q22])]). relacion([sujeto(['Further', analysis, of, total, serum, 'IgE', levels]), verbo([suggested]), complemento([13, q21])]). relacion([sujeto([3, region, are, expression, quantitative, trait, loci, for, 2, nearby, 'genes,', 'ISL2', and, 'proline-serine-threonine', phosphatase]), verbo([interacting]), complemento([protein, 1, '(', 'PSTPIP1),', in, immune, cells])]). relacion([sujeto(['Our', 'GWAS', of, recalcitrant, 'AD', identified, new, susceptibility, regions, containing, genes]), verbo([involved]), complemento([in, epithelial, cell, function, and, immune, 'dysregulation,', 2, key, features, of, 'AD,', and, potentially, extend, our, understanding, of, their, role, in, pathogenesis])]). relacion([sujeto(['Primary', angiosarcoma, of, the, bladder, is, very, 'rare,', with, approximately, 30, cases]), verbo([reported]), complemento([in, the, literature])]). relacion([sujeto(['Those', with, epithelioid, morphology, are, even, 'rarer,', with, only, 'single-case']), verbo([reports]), complemento([published])]). relacion([sujeto(['Morphologically,', the, tumors, were, composed, of, nests, and, sheets, of, highly, atypical, cells, with, high]), verbo([nuclear]), complemento([to, cytoplasmic, 'ratio,', occasional, intracytoplasmic, 'lumens,', and, a, hemorrhagic, background])]). relacion([sujeto(['The', tumor]), verbo([involved]), complemento([the, muscularis, propria, in, 5, /, 9, 'patients,', the, periureteric, adipose, tissue, in, 1, 'patient,', and, the, prostate, and, seminal, vesicles, in, 1, patient])]). relacion([sujeto(['Morphologic', features, that, should]), verbo([suggest]), complemento([the, vascular, origin, of, the, tumor, include, highly, atypical, nuclei, with, interspersed, 'erythrocytes,', hemorrhagic, 'background,', and, occasional, intracytoplasmic, lumens])]). relacion([sujeto(['FOXP3']), verbo([increased]), complemento(['significantly,', 'however,', failed, to, downregulate, 'Th2,', 'instead,', the, relation, between, 'Th1', and, 'T', cytotoxic, was, forcibly, limited, by, the, high, level, of, 'FOXP3,', resulting, in, loss, of, their, power, in, defending, the, host, against, both, parasite, and, carcinogenic, changes])]). relacion([sujeto(['These', results]), verbo([provide]), complemento([more, clarification, for, the, immune, evasion, process, played, by, the, parasite, and, tumor, cells, under, the, supervision, of, 'T', regulatory, cells])]). relacion([sujeto(['Additionally', a, critical, role, of, 'FOXP3', is]), verbo([suggested]), complemento([in, manipulating, 'STAT4', and, 'CD8', in, favor, of, malignant, transformation, in, this, 'life-threatening', parasite])]). relacion([sujeto(['However,', their, importance, in, the, pathobiology, of, vitiligo]), verbo([have]), complemento([yet, to, be, elucidated])]). relacion([sujeto(['To', evaluate, the, expression, profile, of, two, transcription, 'factors,', 'namely,', 'T-bet,', a, 'Th1-specific', 'T', box, transcription, factor, and, 'GATA']), verbo([binding]), complemento([protein, 3, '(', 'GATA-3),', a, 'Th2-specific', transcription, 'factor,', and, to, measure, expression, levels, of, interferon, '(', 'IFN)-γ', and, interleukin, '(', 'IL)-4', mRNAs, as, the, signature, cytokines, of, 'Th1', and, 'Th2', 'cells,', respectively])]). relacion([sujeto(['These', data]), verbo([suggest]), complemento([additional, implications, for, the, role, of, 'Th1/Th2', balance, in, the, immunopathogenesis, of, vitiligo])]). relacion([sujeto(['We', undertook, a, comparative, study, of, the, novel]), verbo([nuclear]), complemento([marker, 'GATA3', '(', expression, typically, restricted, to, breast, and, urothelial, 'carcinomas)', and, 'GCDFP15', and, mammaglobin])]). relacion([sujeto([2.0e-16, ')', ',']), verbo([suggesting]), complemento([that, 'GATA3', may, represent, a, more, sensitive, marker, of, breast, cancer, than, 'GCDFP15', or, mammaglobin])]). relacion([sujeto([pylori, infection]), verbo([has]), complemento([widely, been, suggested, to, 'trigger gastric', carcinogenesis, through, &, 'quot;inflammation-carcinoma', 'chain"', '(', 'non-atrophic', gastritis, '(', 'NAG)', '→', chronic, atrophic, gastritis, '(', 'CAG)', '→', intestinal, metaplasia, '(', 'IM)', '→', dysplasia, '(', 'DYS)', and, gastric, carcinoma, '(', 'GC))'])]). relacion([sujeto(['Connexin43', '(', 'Cx43)', is, a, major, constituent, of, gap, junction, in, normal, gastric, mucosa, '(', 'NGM)', and, it, is, continuously, 'down-regulated', from, normal, gastric, mucosa, to, precancerous, lesions, or, ultimate, gastric, 'carcinoma,', which, shows, novel]), verbo([target]), complemento([against, gastric, carcinoma, by, preventing, the, 'Cx43', decline])]). relacion([sujeto(['The', transcriptional, 'factor,', 'GATA']), verbo([binding]), complemento([protein, 3, '(', 'GATA-3)', is, the, key, to, regulate, adaptive, immune, 'response,', which, possibly, relates, to, inflammation, toward, malignant, transformation])]). relacion([sujeto([pylori]), verbo([associated]), complemento([gastric, carcinoma])]). relacion([sujeto(['Moreover,', the]), verbo([increased]), complemento(['GATA-3', and, inhibited, 'Cx43', were, confirmed, in, clinical, 'specimens,', 'Mongolian', gerbils, and, normal, gastric, epithelial, cell, line, 'GES-1', with, 'H'])]). relacion([sujeto(['Dual-luciferase', reporter, assay, further, revealed, the, 'GATA-3', as, one, of, 'Cx43', 'down-regulators', by, directly]), verbo([binding]), complemento([to, its, promoters])]). relacion([sujeto(['Together,', the, incremental, 'GATA-3', is]), verbo([found]), complemento([in, 'H'])]). relacion([sujeto([pylori]), verbo([associated]), complemento([gastric, 'carcinogenesis,', which, is, responsible, for, 'Cx43', inhibition, as, well])]). relacion([sujeto(['LEF1', also, directly, augments, expression, of, the, effector, 'fate-specifying', transcription, factor, 'GATA3,', thus]), verbo([promoting]), complemento([the, development, of, 'Th2-like', effector, iNKT, cells, that, produce, 'IL-4,', including, those, that, also, produce, 'interferon-γ'])]). relacion([sujeto(['Our', data]), verbo([reveal]), complemento(['LEF1', as, a, central, regulator, of, iNKT, cell, number, and, 'Th2-type', effector, differentiation])]). relacion([sujeto(['Hyperglycemia', represents, one, of, possible, mediators, for, activation, of, immune, system, and, may, contribute, to, worsening, of, inflammatory, state]), verbo([associated]), complemento([with, obesity])]). relacion([sujeto(['In', 'SAAT,', 'HG']), verbo([induced]), complemento([an, increase, in, the, content, of, 'CD206', negative, 'monocytes/macrophages', '(', 'p<0'])]). relacion([sujeto(['Further,', 'HG']), verbo([promoted]), complemento([an, increase, of, mRNA, levels, of, immune, response, markers, '(', 'CCL2,', 'TLR4,', 'TNFα)', and, lymphocyte, markers, '(', 'CD3g,', 'CD4,', 'CD8a,', 'TBX21,', 'GATA3,', 'FoxP3)', in, 'SAAT', '(', 'p<0'])]). relacion([sujeto(['Acute', 'HG', significantly]), verbo([increased]), complemento([the, content, of, monocytes, and, lymphocytes, in, 'SAAT', of, healthy, obese, women])]). relacion([sujeto(['This', result]), verbo([suggests]), complemento([that, the, 'short-term', 'HG', can, modulate, an, immune, status, of, 'AT', in, obese, subjects])]). relacion([sujeto(['Calcium,', 'magnesium,', 'potassium,', 'sodium,', chloride, and, phosphorus, are, the, major, dietary, minerals]), verbo([involved]), complemento([in, various, biological, functions, and, are, commonly, measured, in, the, blood, serum])]). relacion([sujeto(['While', no, locus, met, the, criteria, for, 'genome-wide', significant, 'association,', our, results, demonstrated, a, nominal, association, of, total, serum, calcium, levels, with, a, missense, variant, in, the, calcium, -, sensing, receptor, '(', 'CASR)', gene, on, 3, q13, '(', 'rs1801725,', 'P', =, 1.96, ×, 10, '(', -, 3, ')', ')', in, the, 'African-American', pediatric, 'cohort,', a, locus, previously]), verbo([reported]), complemento([in, 'Caucasians'])]). relacion([sujeto(['We', further, replicated, two, other, loci]), verbo([associated]), complemento([with, serum, calcium, levels, in, the, 'European-American', cohort, '(', 'rs780094,', 'GCKR,', 'P', =, 4.26, ×, 10, '(', -, 3, ')', ;, 'rs10491003,', 'GATA3,', 'P', =, 0.02, ')'])]). relacion([sujeto(['In', 'addition,', we, replicated, a, previously]), verbo([reported]), complemento([locus, on, 1, 'q21,', demonstrating, association, of, serum, magnesium, levels, with, 'MUC1', '(', 'rs4072037,', 'P', =, 2.04, ×, 10, '(', -, 6, ')', ')'])]). relacion([sujeto(['Moreover,', in, an, extended, 'gene-based', association, analysis, we, uncovered, evidence, for, association, of, calcium, levels, with, the, previously]), verbo([reported]), complemento([gene, locus, 'DGKD', in, both, 'European-American', children, and, 'African-American', children])]). relacion([sujeto(['Taken', 'together,', our, results, support, a, role, for, 'CASR', and, 'DGKD']), verbo([mediated]), complemento([calcium, regulation, in, both, 'African-American', and, 'European-American', 'children,', and, corroborate, the, association, of, calcium, levels, with, 'GCKR', and, 'GATA3,', and, the, association, of, magnesium, levels, with, 'MUC1', in, the, 'European-American', children])]). relacion([sujeto(['Hypoparathyroidism,', sensorineural, 'deafness,', and, renal, dysgenesis, syndrome, is, an, autosomal, dominant, disease]), verbo([caused]), complemento([by, mutations, in, the, 'GATA3', gene, on, chromosome, 10, p15])]). relacion([sujeto(['The', patient, was, subsequently, diagnosed, and]), verbo([found]), complemento([to, be, a, heterozygote, for, an, insertion, mutation, c])]). relacion([sujeto(['His', father, was, also, confirmed, to]), verbo([have]), complemento([the, same, mutation, in, 'GATA3'])]). relacion([sujeto(['To', develop, more]), verbo([targeted]), complemento(['therapies,', interfering, with, transcription, factor, '(', 'TF)', activity, is, a, promising, strategy])]). relacion([sujeto(['Meta-analysis', was, used, to, identify, differentially]), verbo([expressed]), complemento([genes, '(', 'DEGs)', in, the, lesional, skin, from, psoriasis, patients, '(', n, =, 237, ')'])]). relacion([sujeto(['We', compiled, a, dictionary, of, 2935]), verbo([binding]), complemento([sites, representing, 'empirically-determined', binding, affinities, of, 'TFs', and, unconventional, 'DNA-binding', proteins, '(', 'uDBPs)'])]). relacion([sujeto(['PREs', are]), verbo([recognized]), complemento([by, 'IRF1,', 'ISGF3,', 'NF-kappaB', and, multiple, 'TFs', with, 'helix-turn-helix', '(', 'homeo)', or, other, 'all-alpha-helical', '(', 'high-mobility', 'group)', 'DNA-binding', domains])]). relacion([sujeto(['We', identified, a, limited, set, of, 'DEGs', that, encode, proteins]), verbo([interacting]), complemento([with, 'PRE', 'motifs,', including, 'TFs', '(', 'GATA3,', 'EHF,', 'FOXM1,', 'SOX5)', and, uDBPs, '(', 'AVEN,', 'RBM8A,', 'GPAM,', 'WISP2)'])]). relacion([sujeto(['PREs', were, prominent, within, enhancer, regions, near, 'cytokine-encoding', 'DEGs', '(', 'IL17A,', 'IL19', and, 'IL1B),']), verbo([suggesting]), complemento([that, 'PREs', might, be, incorporated, into, complex, decoy, oligonucleotides, '(', 'cdODNs)'])]). relacion([sujeto(['To', illustrate, this, 'idea,', we, designed, a, cdODN, to, concomitantly]), verbo([target]), complemento(['psoriasis-activated', 'TFs', '(', i])]). relacion([sujeto(['This', identified, possible, sites, of, 'allele-specific', 'TF/uDBP']), verbo([binding]), complemento([and, showed, that, 'PREs', are, disproportionately, disrupted, by, psoriasis, risk, alleles])]). relacion([sujeto(['We', identified, new, 'TF/uDBP', candidates, and, developed, an, approach, that, '(', 'i)', connects, transcriptome, informatics, to, cdODN, drug, development, and, '(', 'ii)']), verbo([enhances]), complemento([our, ability, to, interpret, 'GWAS', findings])]). relacion([sujeto(['High', 'Rorc', 'CNV', was]), verbo([associated]), complemento([with, the, susceptibility, to, 'BD', '(', 'P', =, 8.99, ×, 10, '(', -, 8, ')', ',', 'OR', =, 3.0, ')', ',', and, low, 'Foxp3', 'CNV', predisposed, to, 'BD', in, female, patients, '(', 'P', =, 1.92, ×, 10, '(', -, 5, ')', ',', 'OR', =, 3.1, ')'])]). relacion([sujeto(['Further', functional, studies, demonstrated, that, the, relative, mRNA, expression, levels, of, 'Rorc', were]), verbo([increased]), complemento([in, individuals, with, high, 'Rorc', copy, 'number,', but, not, for, 'Foxp3'])]). relacion([sujeto(['Increased', production, of, 'IL-1β', and, 'IL-6', was]), verbo([found]), complemento([in, individuals, carrying, a, high, 'CNV', of, 'Rorc'])]). relacion([sujeto(['Our', study, showed, that, high, 'CNVs', of, 'Rorc', and, low, 'CNVs', of, 'Foxp3']), verbo([confer]), complemento([risk, for, 'BD', but, not, for, 'VKH', syndrome])]). relacion([sujeto(['The', tested, 25, 'SNPs', in, 'TBX21,', 'GATA3,', 'Rorc', and, 'Foxp3', did, not]), verbo([associate]), complemento([with, 'BD', and, 'VKH', syndrome])]). relacion([sujeto(['Obesity', is]), verbo([associated]), complemento([with, insulin, resistance, and, inflammation, thought, to, be, caused, by, a, visceral, adipose, tissue, '(', 'VAT)-localized', reduction, in, immunoregulatory, cells, and, increase, in, proinflammatory, immune, cells])]). relacion([sujeto(['We', previously]), verbo([found]), complemento([that, 'VAT', regulatory, 'T', cells, '(', 'Tregs)', normally, express, high, levels, of, 'IL-10', and, that, expression, of, this, cytokine, in, 'VAT', 'Tregs', is, specifically, reduced, in, mice, fed, a, 'high-fat', diet])]). relacion([sujeto(['In', this, 'study,', we, further, investigated, the, phenotype, of, 'VAT', 'Tregs', and]), verbo([found]), complemento([that, the, majority, of, 'IL-10-expressing', 'Tregs', in, the, 'VAT', of, lean, mice, also, expressed, the, 'ST2', chain, of, the, 'IL-33R'])]). relacion([sujeto(['In', addition, to, high, expression, of, 'IL-10,', 'ST2(+)', 'Tregs', in, lean, 'VAT']), verbo([expressed]), complemento([higher, proportions, of, 'Th2-associated', 'proteins,', including, 'GATA3', and, 'CCR4,', and, 'Neuropillin-1', compared, with, 'ST2(-)', 'Tregs'])]). relacion([sujeto(['These', data]), verbo([suggest]), complemento([that, 'IL-33', contributes, to, the, maintenance, of, the, normal, pool, of, 'ST2(+)', 'Tregs', in, the, 'VAT,', and, that, therapeutic, administration, of, 'IL-33', results, in, multiple, 'anti-obesity', 'effects,', including, the, reversal, of, 'VAT', inflammation, and, alleviation, of, insulin, resistance])]). relacion([sujeto(['This', is, a, 'follow-up', study, of, our, previous, work, in, which, we, screened, a, series, of, 'Vasicine', analogues, for, their, 'anti-inflammatory', activity, in, a, preventive, 'OVA']), verbo([induced]), complemento([murine, model, of, asthma])]). relacion([sujeto(['The', study, demonstrated, that, 'R8,', one, of, the, 'analogues,', significantly]), verbo([suppressed]), complemento([the, 'Th2', cytokine, production, and, eosinophil, recruitment, to, the, airways])]). relacion([sujeto(['In', the, present, 'study,', we]), verbo([have]), complemento([been, using, two, standard, experimental, murine, models, of, 'asthma,', where, the, mice, were, treated, with, 'R8', either, during, '(', preventive, 'use)', or, after, '(', therapeutic, 'use)', the, development, of, asthma, features])]). relacion([sujeto(['Also,', the, 'R8', treatment, in, the, therapeutic, model]), verbo([decreased]), complemento([methacholine, induced, 'AHR,', 'Th2', cytokine, 'release,', serum, 'IgE', 'levels,', infiltration, of, inflammatory, cells, into, the, 'airways,', phosphorylation, of, 'STAT6', and, expression, of, 'GATA3'])]). relacion([sujeto(['Moreover,', 'R8', not, only, reduced, goblet, cell, metaplasia, in, asthmatic, mice, but, also, reduced, 'IL-4']), verbo([induced]), complemento(['Muc5AC', gene, expression, in, human, alveolar, basal, epithelial, cells])]). relacion([sujeto(['Further,', 'R8', attenuated, 'IL-4']), verbo([induced]), complemento([differentiation, of, murine, splenocytes, into, 'Th2', cells, in, vitro])]). relacion([sujeto(['So,', we, may, deduce, that, 'R8', treatment, profoundly, reduced, asthma, features, by, attenuating, the, differentiation, of, 'T', cells, into, 'Th2', cells, by, interfering, with, the]), verbo([binding]), complemento([of, 'IL-4', to, its, receptor, in, turn, decreasing, the, phosphorylation, of, 'STAT6', and, expression, of, 'GATA3', in, murine, model, of, asthma])]). relacion([sujeto(['These', preclinical, findings]), verbo([suggest]), complemento([a, possible, therapeutic, role, of, 'R8', in, allergic, asthma])]). relacion([sujeto(['Gata3']), verbo([acts]), complemento([as, a, master, regulator, for, 'T', helper, 2, '(', 'Th2)', cell, differentiation, by, inducing, chromatin, remodeling, of, the, 'Th2', cytokine, 'loci,', accelerating, 'Th2', cell, 'proliferation,', and, repressing, 'Th1', cell, differentiation])]). relacion([sujeto(['Gata3', also, directly, transactivates, the, 'interleukin-5', '(', 'Il5)', gene, via, additional, mechanisms, that]), verbo([have]), complemento([not, been, fully, elucidated])]). relacion([sujeto(['We', herein, identified, a, mechanism, whereby, the, methylation, of, 'Gata3', at, 'Arg-261']), verbo([regulates]), complemento([the, transcriptional, activation, of, the, 'Il5', gene, in, 'Th2', cells])]). relacion([sujeto(['Although', the, 'methylation-mimicking', 'Gata3', mutant]), verbo([retained]), complemento([the, ability, to, induce, 'IL-4', and, repress, 'IFNγ', 'production,', the, 'IL-5', production, was, selectively, impaired])]). relacion([sujeto(['We', also, demonstrated, that, heat, shock, protein, '(', 'Hsp)', 60, strongly]), verbo([associates]), complemento([with, the, 'methylation-mimicking', 'Gata3', mutant, and, negatively, regulates, elongation, of, the, 'Il5', transcript, by, 'RNA', polymerase, 'II'])]). relacion([sujeto(['Thus,', arginine, methylation, appears, to, play, a, pivotal, role, in, the, organization, of, 'Gata3', complexes, and, the]), verbo([target]), complemento([gene, specificity, of, 'Gata3'])]). relacion([sujeto(['In', an, ongoing, screen, for, 'DNA', sequence, variants, that]), verbo([confer]), complemento([risk, of, cutaneous, basal, cell, carcinoma, '(', 'BCC),', we, conduct, a, 'genome-wide', association, study, '(', 'GWAS)', of, 24, ',', 988, ',', 228, 'SNPs', and, small, indels, detected, through, 'whole-genome', sequencing, of, 2, ',', 636, 'Icelanders', and, imputed, into, 4, ',', 572, 'BCC', patients, and, 266, ',', 358, controls])]). relacion([sujeto(['Fine', mapping]), verbo([reveals]), complemento([that, two, variants, correlated, with, 'rs73635312[A]', occur, in, conserved, binding, sites, for, the, 'GATA3', transcription, factor])]). relacion([sujeto(['In', 'addition,', expression, microarrays, and, 'RNA-seq', show, that, 'rs13014235[C]', and, a, related, 'SNP', 'rs700635[C]', are]), verbo([associated]), complemento([with, expression, of, 'CASP8', splice, variants, in, which, sequences, from, intron, 8, are, retained])]). relacion([sujeto(['GATA']), verbo([binding]), complemento([protein, 3, '(', 'GATA3)', is, a, recently, described, immunohistochemical, marker, that, has, proven, useful, in, the, characterization, of, breast, and, urothelial, carcinomas])]). relacion([sujeto(['The', remaining, 2, mesonephric, carcinosarcomas, showed, focal]), verbo([nuclear]), complemento([staining, and, rare, nuclear, 'positivity,', respectively])]). relacion([sujeto(['Of', 36, endocervical, 'adenocarcinomas,', 33, '(', 92, '%', ')', were, negative, for, 'GATA3', and, the, remaining, revealed, focal, weak]), verbo([nuclear]), complemento([staining])]). relacion([sujeto(['Of', 34, endometrial, 'adenocarcinomas,', 32, '(', 94, '%', ')', were, 'negative,', whereas, 2, showed, rare]), verbo([nuclear]), complemento([positivity])]). relacion([sujeto(['The', benign, endocervical, epithelium, and, the, benign, endometrium, in, most, cases, lacked, 'GATA3', 'expression,', whereas, the, benign, squamous, epithelium, in, the, majority, exhibited]), verbo([nuclear]), complemento([basal, and, parabasal, staining, pattern])]). relacion([sujeto(['Our', study, demonstrates, that, 'GATA3', protein, is]), verbo([expressed]), complemento([in, most, mesonephric, 'lesions,', regardless, of, them, being, benign, or, malignant])]). relacion([sujeto(['Multifocal', breast, cancer, '(', 'MFBC),', defined, as, multiple, synchronous, unilateral, lesions, of, invasive, breast, 'cancer,', is, relatively, frequent, and]), verbo([has]), complemento([been, associated, with, more, aggressive, features, than, unifocal, cancer])]). relacion([sujeto(['Characterization', of, different, lesions, from, 36, patients, with, ductal, 'MFBC']), verbo([involved]), complemento([the, identification, of, 'non-silent', coding, mutations, in, 360, 'protein-coding', genes, '(', 171, tumour, and, 36, matched, normal, 'samples)'])]). relacion([sujeto(['Mutations', were, classified, as, '\'', 'oncogenic\'', in, the, case, of, recurrent, substitutions]), verbo([reported]), complemento([in, 'COSMIC', or, truncating, mutations, affecting, tumour, suppressor, genes])]). relacion([sujeto(['To', 'conclude,', as, the, number, of, molecular]), verbo([targeted]), complemento([therapies, increases, and, trials, driven, by, genomic, screening, are, 'ongoing,', our, findings, highlight, the, presence, of, genomic, 'inter-lesion', heterogeneity, in, 'one-third,', despite, similar, pathological, features])]). relacion([sujeto(['Several', comparative, immunohistochemical, studies]), verbo([have]), complemento([been, 'reported,', but, few, included, significant, clinicopathologic, data, and, none, investigated, cases, of, ovarian, and, breast, carcinomas, from, the, same, patients])]). relacion([sujeto(['All', primary, ovarian, tumors, showed, marked]), verbo([nuclear]), complemento(['pleomorphism,', whereas, only, 2, metastatic, breast, carcinomas, had, 'Grade', 3, nuclei, '(', 'P=0'])]). relacion([sujeto(['Pax-8', and, 'WT-1', expression, were]), verbo([found]), complemento([in, 16, of, 18, '(', 88, '%', ')', and, 13, of, 18, '(', 72, '%', ')', primary, ovarian, 'carcinomas,', respectively])]). relacion([sujeto(['Our', study, demonstrated, that, 'Rb1']), verbo([inhibited]), complemento(['OVA-induced', increases, in, 'RI', and, eosinophil, 'counts;', interleukin, '(', 'IL)-4', was, 'recovered,', and, 'IFN-γlevel', increased, in, bronchoalveolar, lavage, fluid])]). relacion([sujeto(['Histological', studies, demonstrated, that, 'Rb1', substantially]), verbo([inhibited]), complemento(['OVA-induced', eosinophilia, in, lung, tissue])]). relacion([sujeto(['Western', blot, studies, demonstrated, that, 'Rb1', substantially]), verbo([inhibited]), complemento(['GATA3', and, increased, 'T-bet'])]). relacion([sujeto(['These', findings]), verbo([suggest]), complemento([that, 'Rb1', may, effectively, ameliorate, the, progression, of, asthma, and, could, be, used, as, a, therapy, for, patients, with, allergic, asthma])]). relacion([sujeto(['From', all, investigated, 'complexes,', '[', '{', 'RuCl2(η(6)-p-cym)}2μ-{(3-py)COO(CH2CH2O)4CO(3-py)}]', '(', 4, ')', was, selected, for, further, study, because, it, did, not, affect, splenocyte, viability, '(', in, concentration, up, to, 50, 'μM),', but, significantly, reduced, secretion, of, representative, 'Th1', 'cytokine,', 'IFN-γ']), verbo([induced]), complemento([by, 'T', cell, mitogen])]). relacion([sujeto(['Besides', 'IFN-γ,', 4]), verbo([inhibited]), complemento([dose, dependently, expression, and, production, of, representative, 'Th17', 'cytokine,', 'IL-17,', in, these, cells])]). relacion([sujeto(['Also,', 4, significantly]), verbo([increased]), complemento(['CD4(+)CD25(+)FoxP3(+)', 'Treg', cell, frequency, in, the, activated, splenocytes])]). relacion([sujeto(['In', 'conclusion,', 'ruthenium(II)', complex, 4]), verbo([modulates]), complemento([immune, system, cell, functions, in, vitro, by, inhibiting, 'T', cell, differentiation, towards, pathogenic, 'Th1/Th17', phenotype, and, inducing, a, regulatory, phenotype, characterized, by, 'IL-10', and, 'IL-4', 'production,', which, may, provide, novel, therapeutic, opportunities, for, 'immune-inflammatory', 'and/or', autoimmune, disorders])]). relacion([sujeto(['We', recently, described, mycobacterial, peptides, that, are, presented, in, 'HLA-E', and]), verbo([recognized]), complemento([by, 'CD8+', 'T-cells'])]). relacion([sujeto(['Using', 'T-cell', 'cloning,', 'phenotyping,', 'microbiological,', functional, and, 'RNA-expression', 'analyses,', we]), verbo([report]), complemento([here, that, these, 'T-cells', can, exert, cytolytic, or, suppressive, 'functions,', inhibit, mycobacterial, 'growth,', yet, express, 'GATA3,', produce, 'Th2', cytokines, '(', 'IL-4,-5,-10,-13)', and, activate, 'B-cells', via, 'IL-4'])]). relacion([sujeto(['These', results, identify, a, novel, human, 'T-cell', subset, with, an, 'unorthodox,', multifunctional, 'Th2', like, phenotype, and, cytolytic, or, regulatory, 'capacities,', which, is]), verbo([involved]), complemento([in, the, human, immune, response, to, mycobacteria, and, demonstrable, in, active, 'TB', 'patients\'', blood])]). relacion([sujeto(['The', results, challenge, the, current, dogma, that, only, 'Th1', cells, are, able, to]), verbo([inhibit]), complemento(['Mtb', growth, and, clearly, show, that, 'Th2', like, cells, can, strongly, inhibit, outgrowth, of, 'Mtb', from, human, macrophages])]). relacion([sujeto(['Although', 'IgE', epitopes, of, walnut]), verbo([have]), complemento([been, 'studied,', 'CD4(+)', 'T', 'cell-specific', epitopes, for, walnut, remain, uncharacterized])]). relacion([sujeto(['In', 'particular,', the, relationship, of, both, phenotype, and, frequency, of, 'walnut-specific', 'T', cells, to, the, disease]), verbo([have]), complemento([not, been, examined])]). relacion([sujeto(['We', sought, to]), verbo([provide]), complemento([a, thorough, phenotypic, analysis, for, 'walnut-reactive', 'T', cells, in, allergic, and, nonallergic, 'subjects,', particularly, the, relationship, of, phenotypes, and, frequencies, of, 'walnut-specific', 'T', cells, with, the, disease])]). relacion([sujeto(['The', majority, of, these, 'T', cells, in, allergic, subjects]), verbo([have]), complemento([a, 'CCR4(+)', phenotype])]). relacion([sujeto(['A', subset, of, these, 'T', cells]), verbo([express]), complemento(['CCR4(+)CCR6(+)', irrespective, of, the, asthmatic, status, of, the, allergic, subjects])]). relacion([sujeto(['Jug', r, 2, -, specific, 'T-cell', clones, from, allergic, subjects, mainly]), verbo([expressed]), complemento(['GATA3,', 'nonetheless,', a, portion, of, 'T-cell', clones, both, 'GATA3', and, 'RAR-related', orphan, receptor, 'C', '(', 'RORC)', or, 'RORC', 'alone,', confirming, the, presence, of, 'TH2,', 'TH2/TH17,', and, 'TH17', cells])]). relacion([sujeto(['Recent', studies]), verbo([have]), complemento([confirmed, the, utility, of, massively, parallel, sequencing, '(', 'MPS)', in, addressing, genetically, heterogeneous, hereditary, hearing, impairment])]). relacion([sujeto(['By', applying, a, 'MPS', diagnostic, panel]), verbo([targeting]), complemento([129, known, deafness, 'genes,', we, identified, a, novel, frameshift, 'GATA3', 'mutation,', c])]). relacion([sujeto(['The', 'GATA3', haploinsufficiency, is, thought, to, be]), verbo([associated]), complemento([with, the, 'hypoparathyroidism,', sensorineural, 'deafness,', and, renal, dysplasia, '(', 'HDR)', syndrome])]). relacion([sujeto(['To', our, 'knowledge,', this, is, the, first]), verbo([report]), complemento([of, genetic, diagnosis, of, 'HDR', syndrome, before, the, clinical, diagnosis])]). relacion([sujeto(['Genetic', examination, for, multiple, deafness, genes, with, 'MPS', might, be, helpful, in, identifying, certain, types, of, syndromic, hearing]), verbo([loss]), complemento([such, as, 'HDR', 'syndrome,', contributing, to, earlier, diagnosis, and, treatment, of, the, affected, individuals])]). relacion([sujeto(['We', describe, a, hemodialysis, patient, with, hypoparathyroidism, due, to, 'HDR', '(', 'hypoparathyroidism,', sensorineural, 'deafness,', and, renal, 'dysplasia)', syndrome]), verbo([caused]), complemento([by, 'GATA3', mutation])]). relacion([sujeto(['The', mechanistic]), verbo([target]), complemento([of, rapamycin, '(', 'mTOR)', signaling, integrates, diverse, environmental, 'cues,', including, growth, 'factors,', nutrients, and, immunological, signals])]). relacion([sujeto(['Activation', of, mTOR, signaling]), verbo([stimulates]), complemento([protein, synthesis, and, anabolic, metabolism, and, coordinates, cell, 'growth,', proliferation, and, fate, decisions])]). relacion([sujeto(['In', recent, 'years,', mTOR, signaling]), verbo([has]), complemento([been, linked, to, the, entire, spectrum, of, 'T', cell, 'biology,', ranging, from, 'T', cell, development, and, activation, to, lineage, specification, and, memory, formation])]). relacion([sujeto(['Mechanistically,', mTOR, activation, profoundly, affects, the, expression, and, activity, of, many, immunologically, relevant, transcription, factors, to, propagate, immune, signaling, and]), verbo([mediate]), complemento([effector, functions])]). relacion([sujeto(['This', review, discusses, how, mTOR, 'signaling,', through, impinging, upon, transcriptional, 'factors,']), verbo([regulates]), complemento(['T', cell, 'development,', 'activation,', and, effector, and, memory, differentiation])]). relacion([sujeto(['Previously,', we]), verbo([have]), complemento([demonstrated, that, eosinophils, purified, from, peripheral, blood, from, asthma, patients, express, high, levels, of, suppressor, of, cytokine, signaling, 3, '(', 'SOCS3)'])]). relacion([sujeto(['In', this, 'article,', 'SOCS3', gene, silencing, in, eosinophils, from, asthmatics]), verbo([has]), complemento([been, carried, out, to, achieve, a, better, understanding, of, the, suppressor, function, in, eosinophils])]). relacion([sujeto(['SOCS3', siRNA, treatment, drastically, reduced, 'SOCS3', expression, in, 'eosinophils,']), verbo([leading]), complemento([to, an, inhibition, of, the, regulatory, transcription, factors, 'GATA-3', and, 'FoxP3,', also, interleukin, '(', 'IL)-10;', in, 'turn,', an, increased, 'STAT3', phosphorilation, was, observed])]). relacion([sujeto(['The', glucocorticoid, receptor, '(', 'GR)', is, a, member, of, the]), verbo([nuclear]), complemento([receptor, superfamily, of, transcription, 'factors,', which, exerts, 'anti-proliferative', and, 'anti-apoptotic', activities])]). relacion([sujeto(['The', 'GR', is]), verbo([expressed]), complemento([in, a, large, proportion, of, breast, cancer, '(', 'BC)', although, levels, generally, decrease, during, cancer, progression])]). relacion([sujeto(['Nuclear', expression, of, 'GR', was, observed, in, 61.6, '%', of, breast, tumours, and, was]), verbo([associated]), complemento([with, features, of, good, prognosis, including, smaller, tumour, size, and, lower, grade, with, less, pleomorphism, and, low, mitotic, count])]). relacion([sujeto(['In', 'ER-positive', 'tumours,', 'GR', was]), verbo([associated]), complemento([with, other, features, of, favourable, outcome, including, 'FOXA1,', 'GATA3', and, 'BEX1', 'expression,', while, low, 'GR', expression, was, associated, with, high, 'Ki67,', p53, and, 'CD71', expression])]). relacion([sujeto(['GR', expression, is]), verbo([associated]), complemento([with, features, of, good, outcome, but, does, not, provide, prognostic, information, independent, of, 'size,', stage, and, grade])]). relacion([sujeto(['Psoriasis', and, atopic, dermatitis, '(', 'AD)', are, inflammatory, diseases, thought, to, be]), verbo([mediated]), complemento([by, helper, 'T-cell', subtypes, 1, and, 2, '(', 'TH1', and, 'TH2),', respectively])]). relacion([sujeto(['We', evaluated, immunohistochemical, stains, for, 'CD3', and, dual, stains, for, 'CD4', and, 'T-bet,', 'GATA']), verbo([binding]), complemento([protein, 3, '(', 'GATA3),', signal, transducer, and, activator, of, transcription, 3, '(', 'STAT3),', or, basonuclin, 2, '(', 'BNC2),', which, are, transcription, factors, reported, to, be, specific, and, mutually, exclusive, for, 'TH1,', 'TH2,', 'TH17,', and, 'TH22', 'cells,', respectively])]). relacion([sujeto(['We']), verbo([found]), complemento([a, significant, difference, in, the, 'TH1:TH2', ratio, between, chronic, psoriasis, and, chronic, 'AD', '(', 0.26, and, 0.09, ',', 'respectively;', 'P', =])]). relacion([sujeto(['To', examine, whether, 'Shenfu', injection, '(', 'SFI)', reduces, 'post-resuscitation', myocardial, dysfunction, in, a, pig, model, by]), verbo([modulating]), complemento([expression, imbalance, of, transcription, factors, of, regulatory, 'T', 'cell,', namely, 'GATA-3', and, 'T-bet'])]). relacion([sujeto(['The', 'CPR', 'time,', number, of, 'defibrillation,', defibrillation, 'energy,', and, 'ROSC', time, were, significantly]), verbo([decreased]), complemento([in, the, 'EP', and, 'SFI', groups, compared, with, those, in, the, 'NS', group])]). relacion([sujeto(['Compared', with, the, 'NS', 'group,', animals, treated, with, 'SFI', had, minimal, myocardial, intracellular, 'damage,', with]), verbo([decreased]), complemento([heart, rate, '(', 'HR,', 'bpm:', 90.33, ±, 3.79, vs])]). relacion([sujeto([106.83, ±, 5.36, ')', and]), verbo([increased]), complemento([mean, arterial, pressure, '(', 'MAP),', cardiac, output, '(', 'CO),', oxygen, delivery, '(', 'DO₂),', and, oxygen, consumption, '(', 'VO₂)', at, 6, hours, after, 'ROSC', '[', 'MAP', '(', 'mmHg,', 1, mmHg, =, 0.133, 'kPa):', 107.67, ±, 1.96, vs])]). relacion([sujeto(['Compared', with, the, 'NS', groups, at, 24, hours, after, 'ROSC,', level, of, 'IL-4', was, markedly]), verbo([increased]), complemento([in, myocardial, cells, '(', 'ng/L:', 33.8, ±, 3.06, vs])]). relacion([sujeto(['Myocardial', immune, dysfunction, is]), verbo([induced]), complemento([by, 'Th1/Th2', imbalance, following, myocardial, injury, subsequent, to, 'CPR', in, pigs])]). relacion([sujeto(['SFI', can, attenuate, myocardial, injury, and]), verbo([regulate]), complemento([myocardial, immune, 'disorders,', protect, 'post-resuscitation', myocardial, injury, by, modulating, expression, imbalance, of, transcription, factors, 'GATA-3', and, 'T-bet'])]). relacion([sujeto(['Asthma', is, a, serious, global, health, problem, characterised, by, airway, 'inflammation,', airway, epithelial, wall, 'shedding,']), verbo([enhanced]), complemento([mucus, 'production,', increased, 'IgE', levels, and, airway, hyperresponsiveness])]). relacion([sujeto(['The', pathophysiology, of, asthma, is]), verbo([mediated]), complemento([by, 'Th2', cells, which, produce, 'Th2', cytokines, like, 'interleukin-4,', 'interleukin-5,', 'interleukin-13', and, 'interleukin-9'])]). relacion([sujeto(['The', differentiation, of, 'Th2', cells, is]), verbo([induced]), complemento([by, the, transcription, factor, 'GATA3', which, is, activated, by, pSTAT6, via, 'IL-4', signalling])]). relacion([sujeto(['We']), verbo([found]), complemento([that, 'Boswellic', acid, treated, groups, suppressed, allergic, airway, 'inflammation,', 'AHR,', 'OVA-specific', 'IgE', and, 'Th2', cytokines, secretion])]). relacion([sujeto(['It', also]), verbo([suppressed]), complemento([the, expression, of, pSTAT6, and, 'GATA3', in, a, dose, dependent, manner])]). relacion([sujeto(['Our', data]), verbo([suggest]), complemento([that, the, mechanism, by, which, 'Boswellic', acid, effectively, treats, asthma, is, based, on, reductions, of, 'Th2', cytokines, via, inhibition, of, pSTAT6, and, 'GATA-3', expression])]). relacion([sujeto(['Asthma', is, a, serious, health, problem]), verbo([causing]), complemento([significant, mortality, and, morbidity, globally])]). relacion([sujeto(['Persistent', airway, 'inflammation,', airway, 'hyperresponsiveness,']), verbo([increased]), complemento([immunoglobulin, 'E', '(', 'IgE)', levels, and, mucus, hypersecretion, are, key, characteristics, of, the, condition])]). relacion([sujeto(['Asthma', is]), verbo([mediated]), complemento([via, a, dominant, 'T-helper', 2, '(', 'Th2)', immune, 'response,', causing, enhanced, expression, of, 'Th2', cytokines])]). relacion([sujeto(['These', cytokines, are, responsible, for, the, various, pathological, changes]), verbo([associated]), complemento([with, allergic, asthma])]). relacion([sujeto(['It', was]), verbo([found]), complemento([that, 'afzelin‑treated', groups, suppressed, eosinophil, 'infiltration,', allergic, airway, 'inflammation,', airway, 'hyperresponsiveness,', 'OVA-specific', 'IgE', and, 'Th2', cytokine, secretion])]). relacion([sujeto(['The', results, of, the, present, study]), verbo([suggested]), complemento([that, the, therapeutic, mechanism, by, which, afzelin, effectively, treats, asthma, is, based, on, reduction, of, 'Th2', cytokine, via, inhibition, of, 'GATA-binding', protein, 3, transcription, 'factor,', which, is, the, master, regulator, of, 'Th2', cytokine, differentiation, and, production])]). relacion([sujeto(['We', evaluated, novel, breast, specific, 'markers,', androgen, receptor, '(', 'AR)', and, 'GATA']), verbo([binding]), complemento([protein, 3, '(', 'GATA3)', 'immunohistostaining,', for, this, 'differential,', and, compare, to, other, traditional, markers])]). relacion([sujeto(['Chronic', rhinosinusitis, '(', 'CRS)', with, nasal, polyps, '(', 'NPs)', in, 'Western', populations, is]), verbo([associated]), complemento([with, 'TH2', cytokine, polarization])]). relacion([sujeto(['IL-25,', an, 'IL-17', family, 'cytokine,', was, recently]), verbo([reported]), complemento([to, induce, 'TH2-type', immune, responses, and, to, contribute, to, several, allergic, 'diseases,', such, as, atopic, dermatitis, and, asthma])]). relacion([sujeto(['Furthermore,', 'IL-17', receptor, 'B', levels, were, also]), verbo([increased]), complemento([in, immune, cells, of, patients, with, 'NPs', compared, with, those, in, control, subjects])]). relacion([sujeto(['This', treatment, also]), verbo([inhibited]), complemento([expression, of, local, inflammatory, 'cytokines,', such, as, 'IL-4', and, 'IFN-γ'])]). relacion([sujeto(['Furthermore,', expression, of, 'CCL11,', 'CXCL2,', intercellular, adhesion, molecule, 1, ',', and, vascular, cell, adhesion, molecule, 1, in, the, nasal, mucosa, was]), verbo([suppressed]), complemento([in, the, 'anti-IL-25-treated', group])]). relacion([sujeto(['Our', results]), verbo([suggest]), complemento([that, 'IL-25', secreted, from, the, sinonasal, epithelia, and, infiltrating, mast, cells, plays, a, crucial, role, in, the, pathogenesis, of, 'CRS', with, 'NPs', in, 'Asian', patients])]). relacion([sujeto(['In', 'addition,', our, results]), verbo([suggest]), complemento([the, novel, possibility, of, treating, nasal, polyposis, with, 'anti-IL-25', therapy])]). relacion([sujeto(['Exercise']), verbo([increases]), complemento([the, levels, of, circulating, inflammatory, mediators])]). relacion([sujeto(['Serum', levels, of, 'CXCL16,', 'IL-6,', 'TNFα', and, 'IL-10', were, also, significantly]), verbo([increased]), complemento([after, exercise])]). relacion([sujeto(['Increased', mRNA, transcription, of, inflammatory, genes, in, 'PBMCs', may, contribute, to]), verbo([increased]), complemento([level, of, inflammatory, markers, after, an, acute, bout, of, exercise])]). relacion([sujeto(['The']), verbo([increased]), complemento([mRNA, levels, of, 'GATA-3', and, 'TXB21', may, indicate, that, 'T', cell, lymphocytes, are, activated, and, secrete, cytokines, into, the, circulation])]). relacion([sujeto(['Here,', we, used, the, presence, of, disseminated, tumor, cells, '(', 'DTC)', in, the, bone, marrow, to, define, patients, with, early, disseminated, breast, cancer, and, identified, low, retinoic, 'acid-induced', 2, '(', 'RAI2)', expression, to, be, significantly]), verbo([associated]), complemento([with, 'DTC', status])]). relacion([sujeto(['Depletion', of, 'RAI2', protein, in, luminal, breast, cancer, cell, lines, resulted, in, dedifferentiation, marked, by, downregulation, of, 'ERα,', 'FOXA1,', and, 'GATA3,', together, with]), verbo([increased]), complemento([invasiveness, and, activation, of, 'AKT', signaling])]). relacion([sujeto(['Functional', analysis, of, the, previously, uncharacterized, 'RAI2', protein, revealed, molecular, interaction, with, 'CtBP', transcriptional, regulators, and, an, overlapping, function, in, controlling, the, expression, of, a, number, of, key]), verbo([target]), complemento([genes, involved, in, breast, cancer])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, 'RAI2', is, a, new, 'metastasis-associated', protein, that, sustains, differentiation, of, luminal, breast, epithelial, cells])]). relacion([sujeto(['We', identified, downregulation, of, 'RAI2', as, a, novel, 'metastasis-associated', genetic, alteration, especially]), verbo([associated]), complemento([with, early, occurring, bone, metastasis, in, 'ERα-positive', breast, tumors])]). relacion([sujeto(['Rapid', advancements, in, massively, parallel, sequencing, methods]), verbo([have]), complemento([enabled, the, analysis, of, breast, cancer, genomes, at, an, unprecedented, 'resolution,', which, have, revealed, the, remarkable, heterogeneity, of, the, disease])]). relacion([sujeto(['It']), verbo([has]), complemento([become, apparent, that, there, are, very, few, highly, recurrently, mutated, genes, such, as, 'TP53,', 'PIK3CA,', and, 'GATA3,', that, no, two, breast, cancers, display, an, identical, repertoire, of, somatic, genetic, alterations, at, 'base-pair', resolution, and, that, there, might, not, be, a, single, highly, recurrently, mutated, gene, that, defines, each, of, the, &, 'quot;intrinsic"', subtypes, of, breast, cancer, '(', 'ie,', 'basal-like,', 'HER2-enriched,', luminal, 'A,', and, luminal, 'B)'])]). relacion([sujeto(['Several', biological, phenomena, may, shape, the]), verbo([reported]), complemento([intratumor, genetic, heterogeneity, observed, in, breast, 'cancers,', including, the, different, mutational, processes, and, multiple, types, of, genomic, instability])]). relacion([sujeto(['Groups', 'I-III', survived, in, culture, longer, and, exhibited, the, formation, of, cell, 'clusters,', whereas, groups, 'IV', and, 'V', could, not, be]), verbo([maintained]), complemento([in, culture, for, an, extended, period, of, time])]). relacion([sujeto(['In', groups, 'IV', and, 'V,']), verbo([decreases]), complemento([were, observed, in, the, expression, levels, of, 'CD117', and, 'CD34'])]). relacion([sujeto(['Cells', were]), verbo([found]), complemento([to, be, capable, of, survival, 'post-cryopreservation', and, exhibited, varying, abilities, to, form, colonies, in, a, methylcellulose, 'matrix,', depending, on, gestational, age])]). relacion([sujeto(['Thus,', we]), verbo([have]), complemento([successfully, isolated, and, characterized, haematopoietic, cells, from, the, bovine, embryo, yolk, sac, at, varying, gestational, ages])]). relacion([sujeto(['Atoh1', '(', 'Math1)', was, the, first, gene, discovered, in, ear, development, that, showed, no, hair, cell, '(', 'HC)', differentiation, when, absent, and, could]), verbo([induce]), complemento(['HC', differentiation, when, misexpressed])]). relacion([sujeto(['However,', other, gene, mutations, also, result, in]), verbo([loss]), complemento([of, initially, forming, 'HCs,', notably, null, mutants, for, 'Pou4f3,', 'Barhl1,', and, 'Gfi1'])]). relacion([sujeto(['HC', development, and, maintenance, also, depend, on, the, expression, of, other, genes, '(', 'Sox2,', 'Eya1,', 'Gata3,', 'Pax2)', and, several, genes]), verbo([have]), complemento([been, identified, that, can, induce, 'HCs', when, misexpressed, '(', 'Jag1)', or, knocked, out, '(', 'Lmo4)'])]). relacion([sujeto(['In', the, ear, 'Atoh1', is, not, only]), verbo([expressed]), complemento([in, 'HCs', but, also, in, some, supporting, cells, and, neurons, that, do, not, differentiate, into, 'HCs'])]). relacion([sujeto(['Simple', removal, of, one, 'gene,', 'Neurod1,', can, 'de-repress', 'Atoh1', and, turns, those, neurons, into, 'HCs']), verbo([suggesting]), complemento([that, 'Neurod1', blocks, 'Atoh1', function, in, neurons])]). relacion([sujeto(['Atoh1', expression, in, inner, pillar, cells, may, also, be, blocked, by, too, many, 'Hes/Hey', factors, but, conversion, into, 'HCs']), verbo([has]), complemento([only, partially, been, achieved, through, 'Hes/Hey', removal])]). relacion([sujeto(['Atoh1', is, a, potent, differentiation, factor, but, can, differentiate, and]), verbo([maintain]), complemento(['HCs', only, in, the, ear, and, when, other, factors, are, 'co-expressed'])]). relacion([sujeto(['Upstream', factors, are, essential, to]), verbo([regulate]), complemento(['Atoh1', level, of, expression, duration, while, 'downstream,', 'co-activated', by, other, 'factors,', will, define, the, context, of, 'Atoh1', action])]). relacion([sujeto(['We']), verbo([suggest]), complemento([that, these, insights, need, to, be, taken, into, consideration, and, approaches, beyond, the, simple, 'Atoh1', expression, need, to, be, designed, able, to, generate, the, radial, and, longitudinal, variations, in, hair, cell, types, for, normal, function, of, the, organ, of, 'Corti'])]). relacion([sujeto(['Although', previous, studies]), verbo([have]), complemento([attempted, to, separate, these, tumors, with, various, immunohistochemical, 'panels,', those, series, have, been, limited, by, small, numbers, of, patients, as, well, as, the, inclusion, of, benign, sweat, gland, tumors])]). relacion([sujeto(['These', data]), verbo([suggest]), complemento([that, p63, and, 'CK5/6', are, specific, determinants, for, sweat, gland, carcinoma, in, the, stated, setting])]). relacion([sujeto(['This', diagnostic, scenario, continues, to]), verbo([require]), complemento([the, procurement, of, a, detailed, clinical, history, regarding, the, number, and, duration, of, skin, lesions, in, any, given, case])]). relacion([sujeto(['T', follicular, helper, '(', 'Tfh)', cells, are, essential, for, efficient, 'B', cell, 'responses,', yet, the, factors, that]), verbo([regulate]), complemento([differentiation, of, this, 'CD4(+)', 'T', cell, subset, are, incompletely, understood])]). relacion([sujeto(['Here', we]), verbo([found]), complemento([that, the, 'KLF2', transcription, factor, serves, to, restrain, 'Tfh', cell, generation])]). relacion([sujeto(['Induced', 'KLF2', deficiency, in]), verbo([activated]), complemento(['CD4(+)', 'T', cells, led, to, increased, 'Tfh', cell, generation, and, 'B', cell, 'priming,', whereas, 'KLF2', overexpression, prevented, 'Tfh', cell, production])]). relacion([sujeto(['KLF2']), verbo([promotes]), complemento([expression, of, the, trafficking, receptor, 'S1PR1,', and, 'S1PR1', downregulation, is, essential, for, efficient, 'Tfh', cell, production])]). relacion([sujeto(['However,', 'KLF2', also]), verbo([induced]), complemento([expression, of, the, transcription, factor, 'Blimp-1,', which, repressed, transcription, factor, 'Bcl-6', and, thereby, impaired, 'Tfh', cell, differentiation])]). relacion([sujeto(['Furthermore,', 'KLF2']), verbo([induced]), complemento([expression, of, the, transcription, factors, 'T-bet', and, 'GATA3', and, enhanced, 'Th1', differentiation])]). relacion([sujeto(['Ideal', potential, vaccine, adjuvants, to]), verbo([stimulate]), complemento([a, 'Th1', immune, response, are, urgently, needed, to, control, intracellular, infections, in, clinical, applications])]). relacion([sujeto(['Therefore,', we, investigated, whether, 'TBG']), verbo([enhances]), complemento([the, 'Th1', immune, response, to, ovalbumin, '(', 'OVA)', and, 'formalin-inactivated', 'Salmonella', typhimurium, '(', 'FIST)', in, mice])]). relacion([sujeto(['TBG', also, dramatically]), verbo([enhanced]), complemento([splenocyte, proliferative, responses, to, concanavalin, 'A,', 'lipopolysaccharide,', and, 'OVA', and, substantially, increased, 'T-bet', mRNA, levels, and, the, 'CD3(+)/CD3(+)CD4(+)/CD3(+)CD8(+)', phenotype, in, splenocytes, from, 'OVA-immunized', mice])]). relacion([sujeto(['In', in, vivo, protection, 'studies,', 'TBG', significantly]), verbo([decreased]), complemento([the, bacterial, burdens, in, the, spleen, and, prolonged, the, survival, time, of, 'FIST-immunized', mice, challenged, with, live, 'S'])]). relacion([sujeto(['In', vivo, neutralization, of, 'IFNγ', with, 'anti-IFNγ', mAbs]), verbo([led]), complemento([to, a, significant, reduction, in, 'FIST-specific', 'IgG2a', and, 'IFNγ', levels, and, in, 'anti-Salmonella', effect, in, 'TBG/FIST-immunized', mice])]). relacion([sujeto(['In', 'conclusion,', these, results]), verbo([suggest]), complemento([that, 'TBG', enhances, a, 'Th1', immune, response, to, control, intracellular, infections])]). relacion([sujeto(['This', study]), verbo([found]), complemento([in, the, level, of, transcription, factors, in, 'CLL', patients, that, with, the, process, of, 'disease,', the, balance, shifts, from, 'Th1/Th2', and, 'Th17/Treg', to, 'Th17', and, 'Treg,', and, 'Treg', cell, may, play, a, critical, immunosuppressive, role, in, the, development, of, 'CLL'])]). relacion([sujeto(['The', 'Usp21-knockout', mice, were]), verbo([found]), complemento([to, be, viable, and, 'fertile,', with, no, significant, 'dysmorphology,', in, contrast, to, the, 'GATA3', and, 'RIPK1', knockout, lines, that, exhibit, embryonic, or, perinatal, lethality])]). relacion([sujeto(['The', lymphocyte, family]), verbo([has]), complemento([expanded, significantly, in, recent, years, to, include, not, only, the, adaptive, lymphocytes, '(', 'T', 'cells,', 'B', 'cells)', and, 'NK', 'cells,', but, also, several, additional, innate, lymphoid, cell, '(', 'ILC)', types])]). relacion([sujeto(['ILCs', lack, clonally, distributed, antigen, receptors, characteristic, of, adaptive, lymphocytes, and, instead]), verbo([respond]), complemento([exclusively, to, signaling, via, 'germline-encoded', receptors])]). relacion([sujeto(['ILCs', resemble, 'T', cells, more, closely, than, any, other, leukocyte, lineage, at, the, transcriptome, level, and]), verbo([express]), complemento([many, elements, of, the, core, 'T', cell, transcriptional, 'program,', including, 'Notch,', 'Gata3,', 'Tcf7,', and, 'Bcl11b'])]). relacion([sujeto(['We', present, our, current, understanding, of, the, shared, and, distinct, transcriptional, regulatory, mechanisms]), verbo([involved]), complemento([in, the, development, of, adaptive, 'T', lymphocytes, and, closely, related, 'ILCs'])]). relacion([sujeto(['Here,', we]), verbo([report]), complemento([a, 'fine-mapping', analysis, of, the, 9, q31])]). relacion([sujeto(['Single', nucleotide, polymorphism, '(', 'SNP)', rs676256, was, most, strongly]), verbo([associated]), complemento([with, risk, in, 'Europeans', '(', odds, ratios, '[', 'OR]', =, 0.9, '[', 0.88, -, 0.92, ']', ;, 'P-value', =, 1.58, ×, 10, '(', -, 25, ')', ')'])]). relacion([sujeto(['SNP', 'rs10816625,', but, not, 'rs13294895,', was, also]), verbo([associated]), complemento([with, risk, of, breast, cancer, in, 'Asian', individuals, '(', 'OR', =, 1.12, '[', 1.06, -, 1.18, ']', ;, 'P-value', =, 2.77, ×, 10, '(', -, 5, ')', ')'])]). relacion([sujeto(['Functional', genomic, annotation, using, data, derived, from, breast, cancer, 'cell-line', models, indicates, that, these, 'SNPs', localise, to, putative, enhancer, elements, that]), verbo([bind]), complemento([known, drivers, of, 'hormone-dependent', breast, 'cancer,', including, 'ER-α,', 'FOXA1', and, 'GATA-3'])]). relacion([sujeto(['In', vitro, analyses, indicate, that, rs10816625, and, rs13294895]), verbo([have]), complemento(['allele-specific', effects, on, enhancer, activity, and, suggest, chromatin, interactions, with, the, 'KLF4', gene, locus])]). relacion([sujeto(['Analysis', of, associations, using, subjects, with, different, 'ancestry,', combined, with, bioinformatic, and, genomic, 'characterisation,', can]), verbo([provide]), complemento([strong, evidence, for, the, likely, causative, alleles, and, their, functional, basis])]). relacion([sujeto(['S100A7', is]), verbo([expressed]), complemento([in, many, squamous, cell, carcinomas, '(', 'SCCs),', such, as, 'SCC', of, the, 'skin,', and, 'well-differentiated', 'SCC', always, displays, stronger, staining, of, this, protein])]). relacion([sujeto(['In', this, 'study,', we, demonstrated, that, the, overexpression, of, 'S100A7', in, 'A431', cells, significantly]), verbo([promoted]), complemento([cell, proliferation, in, vitro, and, tumor, growth, in, 'vivo,', whereas, it, suppressed, the, expression, of, 'GATA-3,', 'caspase-14', and, three, squamous, differentiation, 'markers,', 'keratin-1,', 'TG-1', and, involucrin])]). relacion([sujeto(['Conversely,', the, overexpression, of, 'caspase-14', not, only, significantly]), verbo([decreased]), complemento([cell, proliferation, and, delayed, tumor, growth, but, also, markedly, induced, the, expression, of, three, squamous, differentiation, 'markers,', whereas, 'S100A7', and, 'GATA-3', were, not, influenced])]). relacion([sujeto(['Further', evidence, showed, that, silencing, 'GATA-3', greatly]), verbo([inhibited]), complemento([the, expression, of, 'caspase-14', and, three, differentiation, 'markers,', while, the, expression, of, 'S100A7', was, not, 'changed;', contrary, results, were, obtained, when, overexpressing, 'GATA-3'])]). relacion([sujeto(['Importantly,', restoring, the, expression, of, 'GATA-3', and, 'caspase-14', in, 'A431-S100A7', cells, could, bypass, the, ability, of, 'S100A7', to]), verbo([increase]), complemento([cell, viability, and, repress, squamous, differentiation])]). relacion([sujeto(['These', data]), verbo([suggested]), complemento([that, 'S100A7', expression, in, 'SCC', may, play, an, important, role, in, the, maintenance, of, 'SCC', cell, 'dedifferentiation,', at, least, in, 'SCC', of, the, skin])]). relacion([sujeto(['Kruppel-like', factor, 4, '(', 'KLF4)']), verbo([induces]), complemento([tumorigenesis, or, suppresses, tumor, growth, in, a, 'tissue-dependent', manner])]). relacion([sujeto(['A', 'genome-wide', 'RNA-seq', analysis, was, conducted, to, identify, genes]), verbo([regulated]), complemento([by, 'KLF4', in, 'T-ALL', cells])]). relacion([sujeto(['Chromatin', immunoprecipitation, '(', 'ChIP)', 'PCR', was, used, to, determine, direct]), verbo([binding]), complemento([sites, of, 'KLF4', in, 'T-ALL', cells])]). relacion([sujeto(['Here', we]), verbo([reveal]), complemento([that, 'KLF4', induced, apoptosis, through, the, 'BCL2/BCLXL', pathway, in, human, 'T-ALL', cell, lines, and, primary, 'T-ALL', specimens])]). relacion([sujeto(['We']), verbo([found]), complemento([that, 'KLF4', overexpression, inhibited, 'T', 'cell-associated', genes, including, 'NOTCH1,', 'BCL11B,', 'GATA3,', and, 'TCF7'])]). relacion([sujeto(['Further', mechanistic, studies, revealed, that, 'KLF4', directly]), verbo([bound]), complemento([to, the, promoters, of, 'NOTCH1,', 'BCL2,', and, 'CXCR4', and, suppressed, their, expression])]). relacion([sujeto(['Additionally,', 'KLF4']), verbo([induced]), complemento(['SUMOylation', and, degradation, of, 'BCL11B'])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, 'KLF4', as, a, major, transcription, factor, that, suppresses, the, expression, of, 'T-cell', associated, 'genes,', thus, inhibiting, 'T-ALL', progression])]). relacion([sujeto(['Both', diseases, may, be, exacerbated, by, environmental, 'factors,', 'however,', the, molecular, profiles, of, disease, episodes]), verbo([have]), complemento([not, been, comprehensively, studied])]). relacion([sujeto(['We', identified, differences, in, gene, and, protein, expression, profiles]), verbo([expressed]), complemento([by, peripheral, blood, mononuclear, cells, '(', 'PBMC)', of, 'COPD', 'patients,', patients, with, atopic, asthma, and, healthy, subjects, when, challenged, with, exacerbating, factors, in, 'vitro:', lipopolysaccharide, '(', 'LPS),', house, dust, mite, '(', 'HDM)', and, cat, allergen])]). relacion([sujeto(['PBMC', isolated, from, patients, with, severe, atopic, asthma, and, 'COPD,', as, well, as, healthy, subjects, were]), verbo([stimulated]), complemento([with, rDer, p, 1, 'DG,', rFel, d, 1, 'DG', and, 'LPS'])]). relacion([sujeto(['LPS']), verbo([induced]), complemento([significant, expression, of, 'ANXA1', and, 'LTA4H', in, asthmatics, when, compared, to, 'COPD', patients, and, healthy, subjects])]). relacion([sujeto(['SOX6,STAT4', and, 'IL1RL1', were]), verbo([induced]), complemento([in, 'COPD', after, 'LPS', stimulation])]). relacion([sujeto(['Ribavirin', is, a, synthetic, nucleotide, analog, capable, of]), verbo([inhibiting]), complemento([or, even, preventing, some, viral, infections, in, mammals, and, also, in, fish])]). relacion([sujeto(['It']), verbo([has]), complemento([been, seen, by, others, that, ribavirin, by, itself, is, able, to, stimulate, the, immune, system, of, 'mammals,', causing, a, differentiation, of, 'T-cells', to, 'T', helper, 1, cells, '(', 'Th)-1'])]). relacion([sujeto(['The', results, show, that, ribavirin, administered, orally, in, food, to, 'Atlantic', salmon]), verbo([increased]), complemento(['IFNγ', and, 'CD4', transcripts, in, the, in, vivo, assays, 'and,', in, 'addition,', increased, 'IL-12,', 'IL-15', and, 'CD8', in, the, in, vitro, 'analyses,', indicating, that, the, treatment, stimulates, a, 'Th1', type, response, in, salmon])]). relacion([sujeto(['We']), verbo([have]), complemento([examined, the, role, of, 'GSK3', in, production, of, 'IL-10', by, subsets, of, 'CD4(+)', 'T', helper, cells])]). relacion([sujeto(['However,', treatment, of, 'Th1', and, 'Th2', cells, with, 'GSK3', inhibitors, dramatically]), verbo([increased]), complemento([production, of, 'IL-10'])]). relacion([sujeto(['GSK3', inhibition, also]), verbo([led]), complemento([to, upregulation, of, 'IL-10', among, 'Th1,', 'Th2,', and, 'Th17', subsets, isolated, from, human, blood])]). relacion([sujeto(['Additionally,', 'GSK3', inhibition]), verbo([increased]), complemento([expression, of, the, transcription, factors, 'c-Maf,', 'Nfil3,', and, 'GATA3,', correlating, with, the, increase, in, 'IL-10'])]). relacion([sujeto(['Infants', that, develop, severe, bronchiolitis, due, to, respiratory, syncytial, virus, '(', 'RSV)', are, at]), verbo([increased]), complemento([risk, of, developing, asthma, later, in, life])]). relacion([sujeto(['The', enzyme, indoleamine, 2, ',', 3, -, dioxygenase, '(', 'IDO)']), verbo([has]), complemento([been, reported, to, induce, selective, apoptosis, of, 'T', helper, 1, '(', 'Th1)', cells, and, contributed, to, 'Th2-biased', immune, responses])]). relacion([sujeto(['To', determine, whether, 'RSV', infection, in, vitro, could]), verbo([induce]), complemento(['IDO', expression, and, bioactivity, in, human, dendritic, 'cells,', leading, to, a, 'Th2-biased', immune, response])]). relacion([sujeto(['We']), verbo([found]), complemento([that, moDC, were, infected, by, 'RSV', and, that, this, induced, 'IDO', activation])]). relacion([sujeto(['RSV-induced', 'IDO', activity, was]), verbo([inhibited]), complemento([by, 'palivizumab,', 'UV', 'inactivation,', 'TL4R', 'inhibition,', and, ribavirin])]). relacion([sujeto(['However,', blocking, endosomal, 'TLR', function, with, chloroquine, did, not]), verbo([inhibit]), complemento(['IDO', activity])]). relacion([sujeto(['Selective', inhibitors]), verbo([suggested]), complemento([that, 'RSV-induced', 'IDO', activity, was, dependent, on, the, retinoic, 'acid-inducible', 'gene-I', '(', 'RIG-I)', related, pathway, via, 'NF-κB', and, p38, 'MAPK'])]). relacion([sujeto(['Coculture', of, 'RSV-infected', moDC, with]), verbo([activated]), complemento(['T', 'cells,', in, a, transwell, 'system,', suppressed, expression, of, 'T-bet', '(', a, 'Th1-associated', 'factor)', but, not, 'GATA3', '(', a, 'Th2', 'regulator)'])]). relacion([sujeto(['Our', data, show, for, the, first, time, that, 'RSV', can]), verbo([induce]), complemento([the, expression, and, bioactivity, of, 'IDO', in, human, 'moDC,', in, a, virus, 'replication-dependant', fashion])]). relacion([sujeto(['We']), verbo([suggest]), complemento([that, 'RSV', activation, of, 'IDO', could, be, a, potential, mechanism, for, the, development, of, allergic, diseases])]). relacion([sujeto(['Distinguishing', between, invasive, urothelial, carcinoma, from, other, genitourinary, lesions, such, as, prostatic, and, renal, carcinomas, can, be, 'difficult,', and, may]), verbo([require]), complemento([highly, sensitive, immunohistochemical, markers])]). relacion([sujeto(['GATA-binding', protein, 3, '(', 'GATA3)']), verbo([has]), complemento([been, reported, in, a, high, percentage, of, urothelial, and, breast, carcinomas])]). relacion([sujeto(['Mouse', monoclonal, uroplakin, 'II', '(', 'UPII)', and, p40, antibodies]), verbo([have]), complemento([recently, been, developed, and, demonstrated, high, specificity, in, urothelial, carcinoma])]). relacion([sujeto(['To', investigate, whether, cellular, immunity, and, humoral, immunity, are]), verbo([involved]), complemento([in, trichlorethylene, '(', 'TCE)-induced', mixed, 'allergy,', then, provide, the, scientific, basis, for, the, mechanism, of, this, disease])]). relacion([sujeto(['TCE']), verbo([induced]), complemento([obvious, skin, allergic, reaction, in, guinea, 'pigs,', the, sensitization, rate, was, 83.3, '%', ',', 'IgG', levels, in, 'TCE', group, and, positive, control, increased, significantly])]). relacion([sujeto(['The', lymphocytes, 'CD3⁺', ratio, in, 'TCE', group, and, positive, control, of, rats, was, higher, than, that, in, negative, 'control,', we]), verbo([found]), complemento([that, there, was, no, statistical, difference, of, 'CD4⁺,', 'CD8⁺,', 'CD4⁺/CD8⁺', between, 'TCE', group, and, negative, control, of, rats])]). relacion([sujeto(['The', mRNA, expression, levels, of, 'Foxp3,', 'GATA3,', 'CTLA4', in, 'TCE', patients]), verbo([increased]), complemento([by, 115, '%', ',', 97, '%', ',', 241, '%', ',', respectively, as, compared, with, the, 'control,', 'T-bet', levels, decreased, by, 47, '%', when, compared, with, the, control])]). relacion([sujeto(['TCE', could]), verbo([induce]), complemento([obvious, changes, of, cellular, immunity, and, humoral, immunity, in, guinea, 'pigs,', 'rats,', and, 'TCE', 'patients,', these, findings, indicated, that, 'TCE-induced', immunological, disorder, belongs, to, the, mixed, allergy, with, involvment, of, cellular, immunity, and, humoral, 'immunity,', the, mixed, allergy, might, be, type, 'IV', and, type, 'II', allergy])]). relacion([sujeto(['In', this, 'study,', we, analyzed, immunohistochemical, markers, on, 'Brenner', tumors, and, their]), verbo([associated]), complemento([mucinous, tumor, to, explore, 'Mullerian', as, well, as, 'Wolffian', and, germ, cell, derivation, and, determine, if, the, mucinous, component, is, independent, or, related, to, the, 'Brenner', tumor])]). relacion([sujeto(['Interestingly,', the, areas, of, mucinous, epithelium, as, well, as, mucinous, 'tumors,', intermixed, and, adjacent, to, the, 'Brenner', 'tumor,', were, negative, for, all, 4, 'markers;', 'however,', occasional, 'basal-like', cells]), verbo([retained]), complemento([expression, of, 'GATA3'])]). relacion([sujeto(['The', immunoprofile, of, mucinous, tumors]), verbo([associated]), complemento([with, 'Brenner', tumors, shares, the, lack, of, 'Mullerian', markers, 'PAX2', and, 'Paired', box, gene, 8, with, the, 'Brenner', tumor, but, differs, in, the, expression, of, 'GATA3', only, in, the, 'Brenner', tumor, component])]). relacion([sujeto(['As', 'results,', we]), verbo([found]), complemento([polarized, 'Th2', immune, 'responses,', efficient, 'Aβ42', antibody, 'levels,', and, disappearance, of, antigen, specific, 'T', cells])]). relacion([sujeto(['In-vivo', 'TNFRSF4/25', antibody, 'co-stimulation']), verbo([enhanced]), complemento(['Aβ42', specific, 'T', cell, responses, with, initial, 'Th2', expansion, and, subsequent, development, of, 'Aβ42', specific, 'CD4+CD25+Foxp3+', cells])]). relacion([sujeto(['Notch', is, a, 'single-pass', transmembrane, receptor, protein]), verbo([expressed]), complemento([by, 'T', 'cells,', which, contributes, to, the, pathogenesis, of, asthma, through, regulation, of, the, development, and, differentiation, of, 'T', cells])]). relacion([sujeto(['γ-Secretase', inhibitor, '(', 'GSI)']), verbo([acts]), complemento([as, an, effective, blocker, of, 'Notch', signalling])]). relacion([sujeto(['The', expression, of, 'IL-4,', 'IL-5,', 'IFN-γ,', 'Notch1', signalling, and, 'pro-inflammatory', transcription, factors, in]), verbo([activated]), complemento([lung, 'T', cells, was, evaluated])]). relacion([sujeto(['The', expression, of, 'IL-4', and, 'IL-5']), verbo([decreased]), complemento([and, that, of, 'IFN-γ', increased, 'significantly,', and, the, protein, expression, levels, of, 'pro-inflammatory', transcription, factors, reduced, in, active, lung, 'T', cells, after, administration, of, 'MW167,', compared, to, the, control, group])]). relacion([sujeto(['MW167', treatment]), verbo([prevented]), complemento(['OVA-induced', airway, inflammation, and, histological, changes])]). relacion([sujeto(['The', serum, and, bronchoalveolar, lavage, fluid, '(', 'BALF)', levels, of, 'IL-4', and, 'IL-5', in, 'MW167-treated', mice]), verbo([decreased]), complemento(['significantly,', whereas, those, of, 'IFN-γ', 'increased,', relative, to, the, levels, in, 'OVA-challenged', animals, treated, with, 'PBS'])]). relacion([sujeto(['Our', findings, indicate, that, 'Notch', signalling, plays, an, important, role, in, the, pathogenesis, of, asthma, and, that, 'MW167', may, be, a, potential, therapeutic]), verbo([target]), complemento([for, 'allergen-induced', airway, inflammation])]). relacion([sujeto(['Allergy', to, 'cow\'s', milk]), verbo([increases]), complemento([the, risk, of, sensitization, to, other, foods, in, young, children])]). relacion([sujeto(['After', sensitization, to, 'peanut,', mice, were, exposed, to, a, peanut, regimen, known, to]), verbo([induce]), complemento([eosinophilic, esophageal, inflammation])]). relacion([sujeto(['In', 'milk-sensitized', mice, specific, 'EPIT']), verbo([prevented]), complemento([further, sensitization, to, peanut, or, 'HDM'])]). relacion([sujeto(['EPIT', significantly, modified, the, humoral, 'response,', reduced, 'TH2', cytokine, 'levels,']), verbo([decreased]), complemento([eosinophilic, esophageal, 'infiltration,', and, suppressed, airway, hyperresponsiveness])]). relacion([sujeto(['Moreover,', the, adoptive, transfer, of, milk, 'EPIT', 'Treg', cells, completely]), verbo([prevented]), complemento([sensitization, to, peanut, and, 'peanut-induced', anaphylaxis])]). relacion([sujeto(['Milk', 'EPIT']), verbo([enhanced]), complemento([methylation, of, the, 'GATA-3', promoter, region])]). relacion([sujeto([2, ')', ',', 'octamer-binding', transcription, factor, 3, /, 4, '(', 'OCT3/4),', 'spalt-like', transcription, factor, 4, '(', 'SALL4),', 'GATA']), verbo([binding]), complemento([protein, 3, '(', 'GATA-3),', 'sry-related', 'HMG', box, 2, '(', 'SOX2),', 'SOX17,', human, 'T', cell, 'leukemia/lymphoma', 1, '(', 'TCL1),', glypican, 3, ',', melanoma, associated, antigen, 'C2', '(', 'MAGEC2),', and, paired, box, gene, 8, '(', 'Pax8)'])]). relacion([sujeto(['Thirty-one', cases, '(', 97, '%', ')']), verbo([expressed]), complemento(['SOX17,', whereas, 29, cases, '(', 91, '%', ')', were, positive, for, 'OCT3/4', and, 'SALL4,', respectively])]). relacion([sujeto(['Twenty-eight', cases, '(', 88, '%', ')']), verbo([expressed]), complemento(['MAGEC2', and, 'CAM5'])]). relacion([sujeto(['Peripheral', blood, mononuclear, cells, '(', 'PBMCs)', were]), verbo([stimulated]), complemento([with, 'MTB-HAg', to, generate, 'MTB-HAg-activated', 'T', cells, '(', 'MTBAT)', and, expanded, in, the, neutral, condition, or, 'Th2', polarizing, condition])]). relacion([sujeto([γδT, cells, among, 'MTBAT', cultured, in, the, neutral, or, 'Th2', polarizing, condition, predominantly, produced, 'IFN-γ,', whereas, the, percentage, of, 'IFN-γ⁺', αβT, cells, significantly]), verbo([decreased]), complemento([in, the, 'Th2', polarizing, condition, as, the, culture, time, went, by])]). relacion([sujeto(['Compared', with, the, neutral, 'condition,', 'Th0', type, '(', 'IFN-γ⁺', 'IL-4⁺)', γδT, cells, significantly, 'increased,', and, 'Th2', type, '(', 'IFN-γ⁻', 'IL-4⁺)', αβT, cells, also, significantly]), verbo([increased]), complemento([in, the, 'Th2', polarizing, condition])]). relacion([sujeto(['Recently,', these, cells]), verbo([have]), complemento([also, emerged, as, key, players, in, the, development, of, allergic, inflammation, at, multiple, barrier, surfaces])]). relacion([sujeto(['The', epithelial, 'cell-derived', cytokines, 'IL-25,', 'IL-33,', and, 'TSLP']), verbo([regulate]), complemento([the, activation, and, effector, functions, of, 'ILC2s,', and, recent, studies, suggest, that, their, responsiveness, to, these, cytokines, and, other, factors, may, depend, on, their, tissue, environment])]). relacion([sujeto(['In', this, 'review,', we, focus, on, recent, advances, in, our, understanding, of, the, various, factors, that]), verbo([regulate]), complemento(['ILC2', function, in, the, context, of, 'immunity,', 'inflammation,', and, tissue, repair, across, multiple, organ, systems])]). relacion([sujeto(['To', determine, 'T', box]), verbo([expressed]), complemento([in, 'T', cells, '(', 'T', 'bet),', 'GATA', binding, 'protein-3', '(', 'GATA', 3, ')', ',', and, 'retinoid-related', orphan, nuclear, receptor, gammat, '(', 'RORgammat)', in, rats, with, chronic, obstructive, pulmonary, disease, '(', 'COPD)'])]). relacion([sujeto(['Compared', with, the, 'controls,', the, 'COPD', rats, had]), verbo([decreased]), complemento([pulmonary, function, and, expression, of, serum, 'IL-4,', and, increased, 'INF-γ,', 'IL-', 17, ',', 'Th1/Th2,', 'T-bet,', 'T', bet, /, 'GATA-3,', and, 'RORgammat', protein, '(', 'P<0'])]). relacion([sujeto(['Imbalanced', regulation, of, 'T', bet, /, 'GATA', 3, and, 'RORgammat', on, 'Th1/Th2', and, 'Th17', cells, is]), verbo([associated]), complemento([with, the, occurrence, of, 'COPD'])]). relacion([sujeto(['It', is]), verbo([suggested]), complemento([that, regulatory, immune, cells, play, a, critical, role, in, cancer, cell, growth, by, facilitating, cancer, cells, to, escape, from, the, immune, surveillance])]). relacion([sujeto(['The', generation, of, the, immune, regulatory, cells, in, cancer]), verbo([has]), complemento([not, been, fully, understood, yet])]). relacion([sujeto(['The', results, showed, that, exposure, to, 'PolyIC', markedly]), verbo([increased]), complemento([the, expression, of, 'HDGF', in, 'CCL-9'])]). relacion([sujeto(['The', exposure, to, 'HDGF']), verbo([increased]), complemento([the, expression, of, 'Foxp3', and, decreased, the, expression, of, 'GATA3', in, 'CD4(+)', 'T', cells])]). relacion([sujeto(['After', 'activation,', the, 'Foxp3(+)', 'T', cells]), verbo([suppressed]), complemento([the, 'CD8(+)', 'T', cell, proliferation, and, the, release, of, the, cytotoxic, cytokines])]). relacion([sujeto(['Liver', cancer, 'cell-derived', 'HDGF', can]), verbo([induce]), complemento(['Foxp3(+)', 'T', 'cells;', the, latter, has, the, immune, suppressor, functions, on, 'CD8(+)', 'T', cell, activities])]). relacion([sujeto(['Since', disease, pathogenesis, is]), verbo([associated]), complemento([with, host, inflammatory, 'reactions,', we, investigated, whether, 'Th17', responses, could, be, related, to, aggravated, pathology, in, 'HO'])]). relacion([sujeto(['In', addition, to, elevated, frequencies, of, memory, 'CD4+', 'T', 'cells,', individuals, with, 'HO', showed, accentuated, 'Th17', and, 'Th2', profiles, but]), verbo([decreased]), complemento(['CD4+CD25hiFoxp3+', regulatory, 'T', cells])]). relacion([sujeto(['These', profiles, included]), verbo([increased]), complemento(['IL-17A+,', 'IL-4+,', 'RORC2+', and, 'GATA3+CD4+', 'T', cell, populations])]). relacion([sujeto(['This', study]), verbo([provides]), complemento([initial, evidence, that, elevated, frequencies, of, 'Th17', and, 'Th2', cells, form, part, of, the, immune, network, instigating, the, development, of, severe, onchocerciasis])]). relacion([sujeto(['We']), verbo([have]), complemento([demonstrated, previously, that, gross, cystic, disease, fluid, 'protein-15', '(', 'GCDFP-15)', and, mammaglobin, 'A', '(', 'MAM)', are, of, limited, utility, in, 'triple-negative', breast, cancer, '(', 'TNBC)'])]). relacion([sujeto(['GATA-3', is]), verbo([expressed]), complemento([at, a, higher, frequency, by, 'IHC', in, 'TNBC', compared, to, 'GCDFP-15', and, 'MAM,', although, the, tissue, specificity, of, the, latter, markers, may, be, superior])]). relacion([sujeto(['When', evaluating, a, 'triple-negative', 'tumour,', including, 'GATA-3', in, a, panel, of, markers, may]), verbo([increase]), complemento([the, diagnostic, accuracy, for, tissue, origin, in, the, appropriate, clinical, setting])]). relacion([sujeto(['We', determined, whether, 'heat-shock', protein, 'X', '(', 'HspX)', purified, from, 'Mycobacterium', tuberculosis]), verbo([regulates]), complemento([the, 'Th1/Th2', immune, response, in, an, ovalbumin, '(', 'OVA)-induced', murine, model, of, asthma])]). relacion([sujeto(['HspX']), verbo([increased]), complemento(['interferon-gamma,', 'IL-17A,', -, 12, and, transforming, growth, factor, '(', 'TGF)-β', production, and, 'T-bet', gene, expression, but, reduced, 'IL-13', production, and, 'GATA-3', gene, expression])]). relacion([sujeto(['HspX', also]), verbo([inhibited]), complemento([asthmatic, reactions, as, demonstrated, by, an, increase, in, the, number, of, eosinophils, in, bronchoalveolar, lavage, 'fluid,', inflammatory, cell, infiltration, in, lung, 'tissues,', airway, luminal, 'narrowing,', and, airway, 'hyper-responsiveness'])]). relacion([sujeto(['Furthermore,', 'HspX']), verbo([enhanced]), complemento(['OVA-induced', decrease, of, regulatory, 'T', cells, in, the, mediastinal, lymph, nodes])]). relacion([sujeto(['This', study]), verbo([provides]), complemento([evidence, that, 'HspX', plays, critical, roles, in, the, amelioration, of, asthmatic, inflammation, in, mice])]). relacion([sujeto(['These', findings]), verbo([provide]), complemento([new, insights, into, the, immunotherapeutic, role, of, 'HspX', with, respect, to, its, effects, on, a, murine, model, of, asthma])]). relacion([sujeto(['Differentially']), verbo([expressed]), complemento([genes, were, assessed, for, their, correlation, with, the, sequential, organ, failure, '(', 'SOFA)', score])]). relacion([sujeto(['The', expression, levels, of, a, group, of, genes]), verbo([participating]), complemento([in, the, cell, cycle, '(', 'HIST1H1C,', 'CKS2,', 'CCNA2,', 'CDK1,', 'CCNB2,', 'CIT,', 'CCNB1,', 'AURKA,', 'RAD51),', neutrophil, protease, activity, '(', 'ELANE,', 'ADORA3,', 'MPO,', 'MMP8,', 'CTSG),', 'IL-1R', and, 'IL-18R', response, correlated, directly, with, 'SOFA', and, mortality])]). relacion([sujeto(['Genes']), verbo([involved]), complemento([in, 'T', cell, '(', 'LCK,', 'CD3G,', 'CD3D,', 'ZAP70,', 'ICOS,', 'CD3E,', 'CD28,', 'IL2RB,', 'CD8B,', 'CD8A,', 'CD40LG,', 'IL23A,', 'CCL5,', 'SH2D1A,', 'ITK,', 'CD247,', 'TBX21,', 'GATA3,', 'CCR7,', 'LEF1,', 'STAT4)', and, 'NK', cell, immunity, '(', 'CD244,', 'KLRK1,', 'KLRD1)', were, inversely, associated, with, 'SOFA', and, mortality])]). relacion([sujeto(['While', 30, '%', -, 70, '%', of, 'RSV-infected', infants, develop, 'bronchiolitis,', 2, '%']), verbo([require]), complemento([hospitalization])]). relacion([sujeto(['While', 'TLR4', is]), verbo([associated]), complemento([with, these, disease, 'phenotypes,', the, role, of, this, receptor, in, respiratory, syncytial, virus, '(', 'RSV)', pathogenesis, is, controversial])]). relacion([sujeto(['Here,', we, evaluated, the, interaction, between, 'TLR4', and, environmental, factors, in, 'RSV', disease, and, defined, the, immune, mediators]), verbo([associated]), complemento([with, severe, illness])]). relacion([sujeto(['Together,', the, results, of, this, study, identify, environmental, and, genetic, factors, that, influence, 'RSV', pathogenesis, and]), verbo([reveal]), complemento([that, a, high, 'IL-4/IFN-γ', ratio, is, associated, with, severe, disease])]). relacion([sujeto(['Moreover,', these, molecules, should, be, explored, as, potential]), verbo([targets]), complemento([for, therapeutic, intervention])]). relacion([sujeto([1, ')', 'CONCLUSION:', 'T-bet', mRNA, level, was, reduced, whereas, 'GATA-3', mRNA, level, was]), verbo([increased]), complemento([and, 'T-bet/GATA-3', ratio, was, significantly, reduced, in, 'PBMC,', indicating, that, 'Th1/Th2', ratio, was, of, imbalance, at, 'TF', levels, in, 'PBMC', of, 'HCC,', displaying, 'Th2', thrift, phenomena])]). relacion([sujeto(['GATA3', is, a, transcription, 'factor,', which, is]), verbo([involved]), complemento([in, the, growth, and, differentiation, of, several, human, tissues])]). relacion([sujeto(['Immunohistochemical', staining, for, this, marker]), verbo([has]), complemento([proven, to, be, useful, in, recognizing, a, number, of, 'tumors,', most, notably, those, in, the, urinary, tract, and, breasts])]). relacion([sujeto(['To', 'date,', no, study]), verbo([has]), complemento([specifically, assessed, the, distribution, of, 'GATA3', among, different, histomorphologic, subtypes, of, breast, carcinoma])]). relacion([sujeto(['Of', 55, ductal, 'adenocarcinomas,', 51, '(', 92.7, '%', ')']), verbo([expressed]), complemento(['GATA3'])]). relacion([sujeto(['Genome-wide', association, studies, '(', 'GWASs)']), verbo([have]), complemento([revealed, 'SNP', rs889312, on, 5, q11])]). relacion([sujeto([2, to, be]), verbo([associated]), complemento([with, breast, cancer, risk, in, women, of, 'European', ancestry])]). relacion([sujeto(['Multiple', logistic, regression, analyses, identified, three, independent, risk, 'signals:', the, strongest, associations, were, with, 15, correlated, variants, '(', 'iCHAV1),', where, the, minor, allele, of, the, best, 'candidate,', 'rs62355902,']), verbo([associated]), complemento([with, significantly, increased, risks, of, both, 'estrogen-receptor-positive', '(', 'ER(+):', odds, ratio, '[', 'OR]', =, 1.24, ',', 95, '%', confidence, interval, '[', 'CI]', =, 1.21, -, 1.27, ',', ptrend, =, 5.7, &, 'nbsp;×', 10, '(', -, 44, ')', ')', and, 'estrogen-receptor-negative', '(', 'ER(-):', 'OR', =, 1.1, ',', 95, '%', 'CI', =, 1.05, -, 1.15, ',', ptrend, =, 3.0, &, 'nbsp;×', 10, '(', -, 4, ')', ')', tumors])]). relacion([sujeto(['After', adjustment, for, 'rs62355902,', we]), verbo([found]), complemento([evidence, of, association, of, a, further, 173, variants, '(', 'iCHAV2)', containing, three, subsets, with, a, range, of, effects, '(', the, strongest, was, rs113317823, '[', pcond, =, 1.61, &, 'nbsp;×', 10, '(', -, 5, ')', ']', ')', and, five, variants, composing, iCHAV3, '(', lead, 'rs11949391;', 'ER(+):', 'OR', =, 0.9, ',', 95, '%', 'CI', =, 0.87, -, 0.93, ',', pcond, =, 1.4, &, 'nbsp;×', 10, '(', -, 4, ')', ')'])]). relacion([sujeto(['Twenty-six', percent, of, the, prioritized, candidate, variants, coincided, with, four, putative, regulatory, elements, that]), verbo([interact]), complemento([with, the, 'MAP3K1', promoter, through, chromatin, looping, and, affect, 'MAP3K1', promoter, activity])]). relacion([sujeto(['Functional', analysis, indicated, that, the, cancer, risk, alleles, of, four, candidates, '(', rs74345699, and, rs62355900, '[', 'iCHAV1],', rs16886397, '[', 'iCHAV2a],', and, rs17432750, '[', 'iCHAV3])']), verbo([increased]), complemento(['MAP3K1', transcriptional, activity])]). relacion([sujeto(['Chromatin', immunoprecipitation, analysis, revealed, diminished, 'GATA3']), verbo([binding]), complemento([to, the, minor, '(', 'cancer-protective)', allele, of, 'rs17432750,', indicating, a, mechanism, for, its, action])]). relacion([sujeto(['We', propose, that, the, cancer, risk, alleles]), verbo([act]), complemento([to, increase, 'MAP3K1', expression, 'in vivo', and, might, promote, breast, cancer, cell, survival])]). relacion([sujeto(['Prenatal', dexamethasone, exposure]), verbo([has]), complemento([been, reported, to, increase, allergy, potential, in, childhood, possibly, by, interference, with, normal, immunological, development, in, utero])]). relacion([sujeto(['Both', 'Th1', '(', 'T-bet)', and, 'Th2', '(', 'GATA-3)', mRNA, expression, were, shown, to]), verbo([have]), complemento([a, significant, increase, in, the, prenatal, dexamethasone, exposure, group, at, day, 120, '(', 'p<0'])]). relacion([sujeto(['The', plasma, levels, for, 'Th1', '(', 'IFNγ', and, 'IL-2)', and, 'Th2', '(', 'IL-4,', 'IL-5,', 'IL-13)', were]), verbo([found]), complemento([to, have, no, significant, differences, between, the, two, group, '(', 'p>0'])]). relacion([sujeto(['The', mRNA, expression, of, 'Th17', '(', 'RORγt)', showed, a, significant]), verbo([decrease]), complemento([at, 'post-natal', day, 120, as, well, as, the, plasma, level, of, 'IL-17A', at, day, 7, '(', 11.21, '±1'])]). relacion([sujeto(['Cross-fostering', by, a, dexamethasone, exposed, mother, resulted, in, a, significant]), verbo([increase]), complemento([in, 'Th1/Th2', mRNA, expression, '(', 'p<0'])]). relacion([sujeto([5, ')', and]), verbo([decrease]), complemento([of, 'Th17'])]). relacion([sujeto(['Prenatal', dexamethasone, exposure]), verbo([increased]), complemento(['Th1,', 'Th2', and, decreased, 'Th17', expression])]). relacion([sujeto(['Cross-fostering', by, a, dexamethasone, exposed, mother, results, in, more, prominent]), verbo([increase]), complemento([of, 'Th1', and, 'Th2', expression])]). relacion([sujeto(['The', promoter, methylation, status, of, genes]), verbo([involved]), complemento([in, inflammation, and, autoimmunity, was, profiled, using, the, 'Human', 'Inflammatory', 'Response', and, 'Autoimmunity', 'EpiTect', 'Methyl', 'II', 'Signature', 'PCR', 'Array', profiles])]). relacion([sujeto(['Concerning', tissue, samples, we]), verbo([found]), complemento([that, all, hypermethylated, genes, appear, the, same, methylation, pattern, and, confirmed, a, 'moderate-strong', correlation, between, methylation, levels, in, colon, biopsies, and, peripheral, blood, '(', 'Pearson', coefficients, 'r=0'])]). relacion([sujeto(['Prospero', homeobox, 1, '(', 'PROX1)']), verbo([has]), complemento([been, shown, to, function, as, a, tumor, suppressor, gene, or, oncogene, in, various, types, of, 'cancer,', including, oral, squamous, cell, carcinoma, '(', 'OSCC)'])]). relacion([sujeto(['We']), verbo([have]), complemento([previously, identified, 'PROX1', as, a, downregulated, gene, in, 'OSCC'])]). relacion([sujeto(['The', aim, of, this, study, is, to, clarify, the, underlying, mechanism, by, which, 'PROX1']), verbo([regulates]), complemento([tumorigenicity, of, 'OSCC', cells])]). relacion([sujeto(['Methylation', and, amplification, analysis, was, also, performed, to, assess, the, epigenetic, and, genetic, mechanisms]), verbo([involved]), complemento([in, controlling, 'PROX1', expression])]). relacion([sujeto(['OSCC', cell, line, 'SCC9', was, also, transfected, to, stably]), verbo([express]), complemento([the, 'PROX1', gene])]). relacion([sujeto(['PROX1', amplification, was]), verbo([associated]), complemento([with, better, overall, survival])]). relacion([sujeto(['Our', results]), verbo([suggest]), complemento([that, 'PROX1', functions, as, a, tumor, suppressor, gene, in, oral, carcinogenesis])]). relacion([sujeto(['Type-2', innate, lymphoid, cells, '(', 'ILC2)', belong, to, an, expanding, family, of, innate, lymphocytes, that]), verbo([provide]), complemento([a, potent, source, of, immune, effector, cytokines, at, the, initiation, of, immune, responses])]). relacion([sujeto(['Using', experimental, 'models,', 'ILC2']), verbo([have]), complemento([been, implicated, in, allergic, 'diseases,', such, as, asthma, and, atopic, 'dermatitis,', but, also, in, metabolic, homeostasis])]). relacion([sujeto(['Furthermore,', recent]), verbo([reports]), complemento([have, indicated, that, 'ILC2', not, only, play, roles, at, the, initiation, of, 'type-2', immunity, but, can, also, contribute, to, chronic, 'pathology,', such, as, 'fibrosis,', and, can, impact, on, the, priming, of, the, adaptive, 'T-cell', response])]). relacion([sujeto(['FGF', 'Receptors', and, 'FGF', response, genes, are]), verbo([expressed]), complemento([in, the, 'ND,', and, 'FGF', ligands, are, expressed, in, surrounding, tissues])]). relacion([sujeto(['Individual', inhibitors, of, the, 'Erk,', 'p38,', or, 'Jnk', pathways, did, not, affect, duct, 'migration,', but, inhibition, of, all, three, pathways, together, did]), verbo([inhibit]), complemento([migration, of, the, duct])]). relacion([sujeto(['FGF', signaling]), verbo([acts]), complemento([as, a, &, 'quot;motor"', that, is, required, for, duct, 'migration,', but, other, signals, are, needed, to, determine, the, directionality, of, the, duct, migration, pathway])]). relacion([sujeto(['Here,', we]), verbo([report]), complemento([that, 'antigen-specific', antibody, production, was, potentiated, by, 'Peptide-25', derived, from, 'Ag85B', of, 'Mycobacterium', 'tuberculosis,', and, that, the, production, of, 'antigen-specific', 'IgG1', in, particular, was, markedly, 'potentiated;', 'specifically,', this, occurred, because, the, use, of, 'Peptide-25', resulted, in, an, increase, in, the, number, of, 'antigen-specific', 'antibody-producing', cells])]). relacion([sujeto(['The', observed, expression, pattern, of, 'GATA-3', and, 'T-bet']), verbo([suggests]), complemento([that, the, peptide, modulates, the, 'Th1/Th2', balance, during, immunization])]). relacion([sujeto(['HDR', syndrome, is]), verbo([caused]), complemento([by, haploinsufficiency, of, the, 'GATA3', gene, located, on, chromosome, 10, p15])]). relacion([sujeto(['Here,', we]), verbo([report]), complemento([the, case, of, a, 32, -, 'day-old', 'Korean', male, with, 'HDR', syndrome])]). relacion([sujeto(['Auditory', brainstem, response, '(', 'ABR)', testing, revealed, that, the, patient, had, moderate, sensorineural, 'deafness,', with, hearing]), verbo([losses]), complemento([of, 80, dB, at, the, mid, and, higher, frequencies, for, both, ears])]). relacion([sujeto(['Echocardiography']), verbo([finding]), complemento([revealed, secundum, atrial, septal, deftect])]). relacion([sujeto(['Phe51Leufs*144)', in, exon, 1]), verbo([causing]), complemento([a, frameshift, 'mutation,', which, is, a, novel, de, novo, mutation])]). relacion([sujeto(['Therefore,', we]), verbo([suggest]), complemento([that, 'HDR', syndrome, should, be, considered, in, the, differential, diagnosis, in, symptomatic, or, asymptomatic, patients, with, 'hypoparathyroidism,', and, that, renal, ultrasound, or, 'ABR', testing, be, performed, to, prevent, a, missed, diagnosis])]). relacion([sujeto(['This', is, the, first]), verbo([report]), complemento([on, 'Korean', patient, with, confirmed, 'HDR', syndrome, with, novel, mutation])]). relacion([sujeto(['The', methods, basing, on, the]), verbo([targeted]), complemento([regulation, of, differentiation, process, of, the, 'Th-lymphocytes', that, carry, out, the, immune, response, polarization, attract, an, attention, of, scientists, dealing, with, a, correction, of, 'immune-mediated'])]). relacion([sujeto(['In', the, experiments, in, 'vitro,', it]), verbo([has]), complemento([been, first, found, the, recombinant, 'galectin-3', '(', 0.5, 'mg/mL)', 'up-regulating', the, expression, of, transcription, factors, 'Gata-3', and, 'Rorc', mRNAs, and, 'down-regulating', the, mRNA, expression, of, transcription, factors, 'T-bet', and, 'FoxP3'])]). relacion([sujeto(['Up', to, a, concentration, of, 1, 'mg/mL', recombinant, 'galectin-3']), verbo([stimulates]), complemento(['Th-cells', by, 'dose-dependent', 'manner,', whereas, at, higher, concentrations, stimulating, effect, 'weakens,', and, inhibiting, action, starts, prevailing])]). relacion([sujeto(['Thus,', one, can, suppose, that, 'galectin-3', through, regulation, of, lymphocytes, differentiation]), verbo([promote]), complemento([development, of, 'allergic,', autoimmune, and, neoplastic, diseases, that, allows, us, to, consider, the, 'galectin-3', as, a])]). relacion([sujeto([potential]), verbo([target]), complemento([for, therapy, of, these, diseases])]). relacion([sujeto(['Regulatory', 'T', cells, '(', 'Treg', 'cells)', can]), verbo([express]), complemento([the, transcription, factors, 'T-bet', and, 'GATA-3,', but, the, function, of, this, expression, and, whether, such, cells, represent, stable, subsets, is, still, unknown])]). relacion([sujeto(['By', using, various, reporter, 'tools,', we]), verbo([found]), complemento([that, the, expression, of, 'T-bet', and, 'GATA-3', in, 'Treg', cells, was, dynamically, influenced, by, the, cytokine, environment])]). relacion([sujeto(['Treg', 'cell-specific', deletion, of, the, gene, encoding, either, 'T-bet', '(', 'Tbx21)', or, 'GATA-3', '(', 'Gata3)', alone, did, not, result, in]), verbo([loss]), complemento([of, 'Treg', cell, 'function;', 'however,', mice, with, combined, deficiency, in, both, genes, in, 'Treg', cells, developed, severe, 'autoimmune-like', diseases])]). relacion([sujeto(['Thus,', in, the, steady, 'state,']), verbo([activated]), complemento(['Treg', cells, transiently, upregulated, either, 'T-bet', or, 'GATA-3', to, maintain, 'T', cell, homeostasis])]). relacion([sujeto(['Previous', studies]), verbo([have]), complemento([associated, ckβ, with, muscle, 'development;', 'however,', the, molecular, mechanism, underlying, the, transcriptional, regulation, of, ckβ, has, never, been, elucidated])]). relacion([sujeto(['Supershift', and, chromatin, immunoprecipitation, '(', 'ChIP)', assays, further, identified, that, 'GATA3', but, not, 'GATA2', was]), verbo([bound]), complemento([to, the, 'GATA', site, of, ckβ, promoter])]). relacion([sujeto(['In', 'addition,', 'phorbol-12-myristate-13-acetate', '(', 'PMA)']), verbo([decreased]), complemento([ckβ, promoter, activity, through, 'Ets', and, 'GATA', elements])]). relacion([sujeto(['PMA', also]), verbo([decreased]), complemento([the, ckβ, mRNA, and, protein, levels, about, 12, hours, after, the, promoter, activity, was, 'down-regulated'])]). relacion([sujeto(['EMSA', further, revealed, that, 'PMA', treatment]), verbo([increased]), complemento([the, binding, of, both, 'Ets', and, 'GATA', transcription, factors, to, their, respective, 'DNA', elements])]). relacion([sujeto(['The', 'PMA-mediated', repressive, effect, was, abolished, by, chronic, 'PMA', treatment, and, by, treatment, with, the, 'PKC', inhibitor, 'PKC412,', but, not, the, 'PKC', inhibitor, 'Go', 6983, ',']), verbo([suggesting]), complemento(['PKCε', or, 'PKCη', as, the, 'PKC', isozyme, involved, in, the, 'PMA-mediated', repression, of, ckβ, promoter])]). relacion([sujeto(['Further', confirmation, by, using, 'PKC', isozyme, specific, inhibitors, identified, 'PKCε', as, the, isozyme, that]), verbo([mediated]), complemento([the, 'PMA', repression, of, ckβ, promoter])]). relacion([sujeto([cruzi, infection, was]), verbo([associated]), complemento([with, the, production, of, 'pro-', and, 'anti-inflammatory', 'cytokines,', notably, 'IL-27p28,', and, with, the, induction, of, 'T-bet', and, 'IFN-γ', expression, in, 'Treg', cells])]). relacion([sujeto(['Furthermore,', endogenous, glucocorticoids]), verbo([released]), complemento([in, response, to, 'T'])]). relacion([sujeto(['Notably,', 'IL-2', plus, dexamethasone, combined, treatment, before, infection, was]), verbo([associated]), complemento([with, increased, 'Treg', cell, proliferation, and, expression, of, 'GATA-3,', 'IL-4', and, 'IL-10,', and, increased, mice, survival, time])]). relacion([sujeto(['The', transcription, factor, 'GATA3', is]), verbo([involved]), complemento([in, mammary, gland, development, and, is, crucial, for, the, maintenance, of, the, differentiated, status, of, luminal, epithelial, cells])]). relacion([sujeto(['The', role, of, 'GATA3', in, breast, cancer, as, a, tumor, suppressor]), verbo([has]), complemento([been, 'established,', although, insights, into, the, mechanism, of, 'GATA3', expression, loss, are, still, required])]). relacion([sujeto(['Confocal', microscopy, and, in, vitro, phosphorylation, studies, were, conducted, to, examine, progestin, capacity, to]), verbo([induce]), complemento(['GATA3', serine, phosphorylation, in, its, 308, residue])]). relacion([sujeto(['In', the, former, 'mechanism,', the, histone, methyltransferase, enhancer, of, zeste, homolog, 2, is, 'co-recruited', with]), verbo([activated]), complemento(['PR', to, a, putative, progesterone, response, element, in, the, 'GATA3', proximal, 'promoter,', increasing, 'H3K27me3', levels, and, inducing, chromatin, 'compaction,', resulting, in, decreased, 'GATA3', mRNA, levels])]). relacion([sujeto(['This', transcriptional, regulation, is, coupled, with]), verbo([increased]), complemento(['GATA3', protein, turnover, through, 'progestin-induced', 'GATA3', phosphorylation, at, serine, 308, followed, by, 26, 'S', 'proteasome-mediated', degradation])]). relacion([sujeto(['Both', molecular, mechanisms, converge, to, accomplish]), verbo([decreased]), complemento(['GATA3', expression, levels, in, breast, cancer, cells, upon, 'PR', activation])]). relacion([sujeto(['In', 'addition,', we, demonstrated, that]), verbo([decreased]), complemento(['GATA3', levels, are, required, for, 'progestin-induced', upregulation, of, cyclin, 'A2,', which, mediates, the, 'G1', to, 'S', phase, transition, of, the, cell, cycle, and, was, reported, to, be, associated, with, poor, prognosis, in, breast, cancer])]). relacion([sujeto(['Finally,', we, showed, that, downregulation, of, 'GATA3', is]), verbo([required]), complemento([for, progestin, stimulation, of, both, in, vitro, cell, proliferation, and, in, vivo, tumor, growth])]). relacion([sujeto(['In', the, present, 'study,', we]), verbo([reveal]), complemento([that, 'progestin-induced', 'PR', activation, leads, to, loss, of, 'GATA3', expression, in, breast, cancer, cells, through, transcriptional, and, 'post-translational', regulation])]). relacion([sujeto(['Importantly,', we, demonstrate, that, 'GATA3', downregulation, is]), verbo([required]), complemento([for, 'progestin-induced', upregulation, of, cyclin, 'A2', and, for, 'progestin-induced', in, vitro, and, in, vivo, breast, cancer, cell, growth])]). relacion([sujeto(['We', performed, a, 'genome-wide', association, study, '(', 'GWAS)', to, comprehensively, identify, inherited, genetic, variants]), verbo([associated]), complemento([with, susceptibility, to, 'AYA', 'ALL'])]). relacion([sujeto(['The', risk, allele, at, rs3824662, was, most, frequent, in, 'Philadelphia', chromosome, '(', 'Ph)-like', 'ALL', but, also]), verbo([conferred]), complemento([susceptibility, to, 'non-Ph-like', 'ALL', in, 'AYAs'])]). relacion([sujeto(['This', study, was, designed, to]), verbo([reveal]), complemento([the, molecular, and, cellular, mechanisms, underlying, the, effect, of, estrogen, on, 'MS', alleviation])]). relacion([sujeto(['Pregnancy', and, pregnancy, level, of, estrogen, alleviated, clinical, manifestations, in, 'EAE']), verbo([induced]), complemento(['mice,', reduced, 'CNS', demyelination, and, cell, 'infiltration,', suppressed, spleen, 'T', cell, 'proliferation,', enhanced, production, of, 'anti-inflammatory', cytokines, in, splenocytes, and, increased, the, percentage, of, 'Th2', and, 'Treg', cells])]). relacion([sujeto(['Furthermore,', the, results, of, 'real-time', 'PCR', for, transcription, factors, and, related, cytokines, of, 'Th1/Th2/Th17', and, 'Treg', cells, in, 'CNS', showed, reduced, expression, levels, of, 'Th1', and, 'Th17', transcription, 'factors,', including, 'T-bet', and, 'ROR-γt,', and]), verbo([decreased]), complemento(['Th1', and, 'Th17', cytokines, including, 'IFN-γ,', 'TNF-α,', 'IL-17', and, 'IL-23'])]). relacion([sujeto(['These', results, are, the, first, to, indicate, that, pregnancy, and, pregnancy, level, of, estrogen, ameliorate, the, 'EAE', condition, by, favoring, 'Treg', and, 'Th2', differentiation, through]), verbo([induced]), complemento([expression, of, 'Foxp3', and, 'GATA3', in, the, 'CNS'])]). relacion([sujeto(['Moreover,', pregnancy, and, pregnancy, level, of, estrogen]), verbo([decreased]), complemento([mRNA, levels, of, 'T-bet', and, 'ROR-γt', in, the, 'CNS'])]). relacion([sujeto(['Tree', shrew]), verbo([has]), complemento([increasingly, become, an, attractive, experimental, animal, model, for, human, 'diseases,', particularly, for, breast, cancer, due, to, spontaneous, breast, tumours, and, their, close, relationship, to, primates, and, by, extension, to, humans])]). relacion([sujeto(['However,', neither, normal, mammary, glands, nor, breast, tumours]), verbo([have]), complemento([been, well, characterised, in, the, 'Chinese', tree, shrew, '(', 'Tupaia', belangeri, 'chinensis)'])]). relacion([sujeto(['Haematoxylin', and, eosin, '(', 'H&E)', staining, and, immunohistochemistry, '(', 'IHC)', showed, that, normal, mammary, gland, morphology, and, structures, of, tree, shrews, were, quite, similar, to, those]), verbo([found]), complemento([in, humans])]). relacion([sujeto(['DMBA', was, shown, to]), verbo([induce]), complemento([breast, tumours, '(', 12, '%', ')', while, the, addition, of, 'MPA', increased, the, tumour, incidence, '(', 50, '%', ')'])]). relacion([sujeto(['Of', 'these,', three]), verbo([induced]), complemento([breast, tumours, were, intraductal, papillary, carcinomas, and, one, was, invasive, ductal, carcinoma, '(', 'IDC)'])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, tree, shrews, may, be, a, promising, animal, model, for, a, subset, of, human, breast, cancers, with, 'PTEN/PIK3CA', gene, mutations])]). relacion([sujeto(['By']), verbo([binding]), complemento([to, 'T', cell, immunoglobulin, 'mucin-3', '(', 'TIM-3)', on, activated, 'Th1', 'cells,', 'galectin-9', '(', 'Gal-9)', negatively, regulates, 'Th1-type', alloimmunity])]). relacion([sujeto(['TIM-3', induction, in, circulating, 'CD4+', 'T', cells, of, the, 'recipient:', '(', 1, ')', depressed, 'T-bet/IFN-γ,', while, amplifying, 'GATA3', and, 'IL-4/IL-10', expression, in, orthotopic, liver, 'transplants;', '(', 2, ')']), verbo([promoted]), complemento(['T', cell, exhaustion, '(', 'PD-1,', 'LAG-3)', 'phenotype;', and, '(', 3, ')', depressed, neutrophil, and, macrophage, 'infiltration/function', in, orthotopic, liver, transplants])]). relacion([sujeto(['In', parallel, 'studies,', we, documented, for, the, first, time, that, 'Gal-9,', a, natural, 'TIM-3', 'ligand,', was, produced, primarily, by, and]), verbo([released]), complemento([from, 'IR-stressed', 'hepatocytes,', both, in, vivo, and, in, vitro])]). relacion([sujeto(['Moreover,', exogenous, recombinant, 'Gal-9', '(', 'rGal-9)', potentiated, liver, resistance, against, 'IRI', by, depressing, 'T', cell, activation, and]), verbo([promoting]), complemento([apoptosis, of, 'CD4+', 'T', cells])]). relacion([sujeto(['Negative', regulation, by, recipient, 'TIM-3+CD4+', cells]), verbo([provides]), complemento([evidence, for, cytoprotective, functions, of, a, discrete, 'T', cell, 'subset,', which, should, be, spared, when, applying, 'T', 'cell-targeted', immunosuppression, in, transplant, recipients])]). relacion([sujeto(['Thrombopoietin', '(', 'TPO)', is, the, principal, regulator, of, thrombopoiesis, and]), verbo([promotes]), complemento([the, 'proliferation,', differentiation, and, maturation, of, megakaryocytic, progenitor, cells, in, mammals])]). relacion([sujeto(['In', this, study, we]), verbo([report]), complemento([on, the, molecular, and, functional, characterization, of, goldfish, 'TPO'])]). relacion([sujeto(['Significant']), verbo([decrease]), complemento([of, tpo, and, 'c-mpl', expressions, in, goldfish, primary, kidney, macrophage, '(', 'PKM)', 'cultures,', as, progenitor, to, macrophage, development, 'progressed,', indicates, that, 'TPO', is, not, involved, in, monopoiesis])]). relacion([sujeto(['Recombinant', goldfish, 'TPO', '(', 'rgTPO)', alone, did, not]), verbo([induce]), complemento([significant, proliferation, of, progenitor, 'cells,', but, 'TPO', in, cooperation, with, recombinant, goldfish, kit, ligand, 'A', '(', 'rgKITLA)', supported, proliferation, of, progenitor, cells, in, a, 'dose-dependent', manner])]). relacion([sujeto(['Furthermore,', rgTPO, and, rgKITLA, synergistically]), verbo([stimulated]), complemento([thrombocytic, 'colony-formation'])]). relacion([sujeto(['Our', results, demonstrate, that, goldfish, 'TPO']), verbo([has]), complemento([similar, functions, to, mammalian, 'TPO', as, a, regulator, of, 'thrombopoiesis,', and, suggests, a, highly, conserved, molecular, mechanism, of, thrombocyte, development, throughout, evolution, of, vertebrates])]). relacion([sujeto(['UPII', expression, was, compared, with, 'GATA']), verbo([binding]), complemento([protein, 3, '(', 'GATA3)', and, estrogen, receptor, for, its, role, in, facilitating, the, differential, diagnosis, of, the, above, 3, types, of, malignancy])]). relacion([sujeto(['UPII', labeling, was, not]), verbo([found]), complemento([in, any, breast, and, prostate, carcinomas])]). relacion([sujeto(['Estrogen', receptor]), verbo([nuclear]), complemento([labeling, was, seen, in, 13.0, '%', of, 'UCs', and, 12.5, '%', of, prostate, carcinomas])]). relacion([sujeto(['We']), verbo([reported]), complemento([that, 'DNA-dependent', protein, kinase, '(', 'DNA-PK)', is, critical, for, the, expression, of, nuclear, factor, 'κB-dependent', genes, in, 'TNF-α-treated', glioblastoma, 'cells,', suggesting, an, involvement, in, inflammatory, diseases])]). relacion([sujeto(['DNA-PK', inhibition, by, gene, heterozygosity, of, the, 450, -, kDa, catalytic, subunit, of, the, kinase, '(', 'DNA-PKcs(+/-))', also]), verbo([prevented]), complemento([manifestation, of, 'asthma-like', traits])]). relacion([sujeto(['Remarkably,', such, protection, occurred, without]), verbo([causing]), complemento([severe, combined, immunodeficiency])]). relacion([sujeto(['In', mouse, 'CD4(+)', 'T', cells, in, vitro, 'DNA-PK', inhibition, severely, blocked, 'CD3/CD28-induced', 'Gata3', and, 'T-bet', expression, in, 'CD4(+)', 'T', cells, and]), verbo([prevented]), complemento([differentiation, of, 'TH1', and, 'TH2', cells, under, respective, 'TH1-', and, 'TH2-skewing', conditions])]). relacion([sujeto(['Our', results]), verbo([suggest]), complemento(['DNA-PK', as, a, novel, determinant, of, asthma, and, a, potential, target, for, the, treatment, of, the, disease])]). relacion([sujeto(['Inflammatory', dermatoses, showed, epidermal, 'T', cells, predominantly]), verbo([expressing]), complemento(['GATA-3,', except, 'psoriasis,', which, exhibited, a, mixed, 'GATA-3/T-bet', staining])]). relacion([sujeto(['In', 'contrast,', neoplastic, 'T', cells, in, patch, stage, 'MF', showed, markedly]), verbo([increased]), complemento(['T-bet', positivity, with, minimal, 'GATA-3', expression])]). relacion([sujeto(['Conventional', karyotyping, '(', 550, bands, 'resolution)', is, able, to, identify, chromosomal, aberrations, &, 'gt;5-10 Mb,', which, represent, a, known]), verbo([cause]), complemento([of, intellectual, 'disability/developmental', delay, '(', 'ID/DD)', 'and/or', multiple, congenital, anomalies, '(', 'MCA)'])]). relacion([sujeto(['Array-Comparative', 'Genomic', 'Hybridization', '(', 'array-CGH)']), verbo([has]), complemento([increased, the, diagnostic, yield, of, 15, -, 20, '%'])]). relacion([sujeto(['FISH', analysis, could, be, performed, on, six, cases, and, showed, that, rearrangements, were, translocation, 'derivatives,', indistinguishable, from, a, normal, karyotype, as, they]), verbo([involved]), complemento([a, similar, band, pattern, and, size])]). relacion([sujeto(['Genes', spanning, the, rearrangements, could, be]), verbo([associated]), complemento([with, some, phenotypic, features, in, three, cases, '(', case, 3, :, 'DOCK8;', case, 4, :, 'GATA3,', 'AKR1C4;', case, 6, :, 'AS/PWS', 'deletion,', 'CHRNA7),', and, in, 'two,', likely, disease, genes, were, present, '(', case, 5, :, 'NR2F2,', 'TP63,', 'IGF1R;', case, 7, :, 'CDON)'])]). relacion([sujeto(['Large', complex, rearrangements, of, up, to, 18, &, 'nbsp;Mb,']), verbo([involving]), complemento([chromosomal, regions, with, similar, size, and, band, appearance, may, be, overlooked, by, conventional, karyotyping])]). relacion([sujeto(['Currently,', in, the]), verbo([era]), complemento([of, 'post-genomics,', immunology, is, facing, a, challenging, problem, to, translate, mutant, phenotypes, into, gene, functions, based, on, 'high-throughput', 'data,', while, taking, into, account, the, classifications, and, functions, of, immune, 'cells,', which, requires, new, methods])]). relacion([sujeto(['Here', we, propose, a, novel, application, of, a, multidimensional, 'analysis,', 'Canonical', 'Correspondence', 'Analysis', '(', 'CCA),', to]), verbo([reveal]), complemento([the, molecular, characteristics, of, undefined, cells, in, terms, of, cellular, differentiation, programmes, by, analysing, two, transcriptomic, datasets])]). relacion([sujeto(['With', a, new, 'concept,', differentiation, 'variable,', 'CCA']), verbo([provides]), complemento([an, automatic, classification, of, cell, 'samples,', which, had, a, high, sensitivity, and, a, comparable, performance, to, other, classification, methods])]). relacion([sujeto(['In', 'addition,', we, elaborate, how, 'CCA', results, can, be, 'interpreted,', and]), verbo([reveal]), complemento([the, features, of, 'CCA', in, comparison, with, other, visualisation, techniques])]). relacion([sujeto(['CCA', is, a, visualisation, tool, with, a, classification, ability, to]), verbo([reveal]), complemento([the, 'cross-level', relationships, of, 'genes,', cells, and, differentiation, programmes])]). relacion([sujeto(['GATA-3,', 'GCDFP-15', and, 'MGB', were]), verbo([expressed]), complemento([in, 37.9, '%', '(', 370, /, 976, ')', ',', 26.0, '%', '(', 254, /, 978, ')', and, 35.3, '%', '(', 348, /, 986, ')', of, this, cohort, of, 1017, 'IBCs,', respectively])]). relacion([sujeto(['GATA-3', and, 'MGB', were, not]), verbo([associated]), complemento([with, outcome])]). relacion([sujeto(['Understanding', the, molecular, networks, that]), verbo([regulate]), complemento([adipogenesis, is, crucial, for, combating, obesity])]). relacion([sujeto(['However,', the, identity, and, molecular, actions, of, negative, regulators, that]), verbo([regulate]), complemento([the, early, development, of, adipocytes, remain, poorly, understood])]). relacion([sujeto(['Constitutive', overexpression, of, 'CREB3L4', resulted, in, the, inhibition, of, adipocyte, 'differentiation,', whereas, knockdown, of, 'Creb3l4', expression]), verbo([caused]), complemento([differentiation, of, preadipocytes, into, mature, 'adipocytes,', bypassing, the, mitotic, clonal, expansion, step])]). relacion([sujeto(['In', 3, 'T3-L1', 'preadipocytes,', 'Creb3l4', knockdown, resulted, in]), verbo([increased]), complemento([expression, of, peroxisome, 'proliferator-activated', receptor, γ, '(', 'PPARγ2)', and, 'CCAAT/enhancer', binding, protein, '(', 'C/EBPα),', either, by, increasing, the, protein, stability, of, 'C/EBPβ', or, by, decreasing, the, expression, of, 'GATA3,', a, negative, regulator, of, 'PPARγ2', expression])]). relacion([sujeto(['Consequently,']), verbo([increased]), complemento(['PPARγ2', and, 'C/EBPα', levels, induced, adipocyte, 'differentiation,', even, in, the, presence, of, minimal, hormonal, inducer])]). relacion([sujeto(['Thus,', it, can, be, speculated, that, 'CREB3L4']), verbo([has]), complemento([a, role, as, 'gatekeeper,', inhibiting, adipogenesis, in, 3, 'T3-L1', preadipocytes])]). relacion([sujeto(['Moreover,', adipocytes, of, 'Creb3l4-knockout', mice, showed, hyperplasia]), verbo([caused]), complemento([by, increased, 'adipogenesis,', and, exhibited, improved, glucose, tolerance, and, insulin, 'sensitivity,', as, compared, with, littermate, 'wild-type', mice])]). relacion([sujeto(['These', results, raise, the, possibility, that, 'Creb3l4', could, be, a, useful, therapeutic]), verbo([target]), complemento([in, the, fight, against, obesity, and, metabolic, syndrome])]). relacion([sujeto(['GATA']), verbo([binding]), complemento([protein, 3, '(', 'GATA3)', is, a, regulator, of, mammary, luminal, cell, 'differentiation,', and, an, estrogen, receptor, '(', 'ER)', associated, marker, in, breast, cancer])]). relacion([sujeto(['Tumor', suppressor, functions, of, 'GATA3']), verbo([have]), complemento([been, demonstrated, primarily, in, 'basal-like', breast, cancers])]). relacion([sujeto(['GATA3']), verbo([target]), complemento([genes, were, identified, in, 'normal-', and, luminal, 'cancer-', mammary, cells, by, 'ChIP-seq,', followed, by, examination, of, the, effects, of, 'GATA3', expressions, and, mutations, on, 'tumorigenesis-associated', genes, and, processes])]). relacion([sujeto(['Additionally,', mutations, and, expression, data, of, luminal, breast, cancer, patients, from, 'The', 'Cancer', 'Genome', 'Atlas', were, analyzed, to, characterize, genetic, signatures]), verbo([associated]), complemento([with, 'GATA3', mutations])]). relacion([sujeto(['We', show, that, some, 'GATA3', effects, shift, from, tumor]), verbo([suppressing]), complemento([to, tumor, promoting, during, 'tumorigenesis,', with, deregulation, of, three, 'genes,', 'BCL2,', 'DACH1,', 'THSD4,', representing, major, 'GATA3-controlled', processes, in, cancer, progression])]). relacion([sujeto(['In', 'addition,', we, identify, an, altered, activity, of, mutant, 'GATA3,', and, distinct]), verbo([associated]), complemento([genetic, signatures])]). relacion([sujeto(['Circulating', lymphocyte, number, was, significantly]), verbo([decreased]), complemento([in, patients, with, sepsis])]). relacion([sujeto(['From', the, 'above,', the, inflammatory, response, especially, the, adaptive, immune, response, is, still]), verbo([activated]), complemento([in, sepsis, and, severe, 'sepsis,', but, significant, immunosuppression, was, developed, in, septic, shock])]). relacion([sujeto(['In', 'addition,', the, proportion, of, 'Th17/Treg', inversed, may, be]), verbo([associated]), complemento([with, the, illness, aggravation, of, patients, with, sepsis])]). relacion([sujeto(['To', our, 'knowledge,', breast, carcinoma, metastatic, to, a, gastric, hyperplastic, polyp]), verbo([has]), complemento([not, yet, been, reported])]). relacion([sujeto(['The', association, of, 'IL-6', and, 'IL-6', receptor, α, '(', 'IL-6Rα)', with, asthma, was, 'reported,']), verbo([suggesting]), complemento([their, involvement, in, asthma])]). relacion([sujeto(['EM', 'CD8+', 'T', cells]), verbo([expressing]), complemento(['IL-6Rα', '(', 'IL-6Rα(high))', were, identified, in, human, peripheral, blood, and, analyzed, for, 'function,', 'gene,', and, transcription, factor, expression])]). relacion([sujeto(['A', unique, population, of, 'IL-6Rα(high)', 'EM', 'CD8+', 'T', cells, was]), verbo([found]), complemento([in, peripheral, blood])]). relacion([sujeto(['These', cells, that, potently, 'proliferated,', 'survived,', and, produced, high, levels, of, the, 'Th2-type', cytokines, 'IL-5', and, 'IL-13', had]), verbo([increased]), complemento([levels, of, 'GATA3', and, decreased, levels, of, 'T-bet', and, 'Blimp-1', in, comparison, with, other, 'EM', 'CD8+', 'T', cells])]). relacion([sujeto(['In', 'fact,', 'GATA3', was]), verbo([required]), complemento([for, 'IL-6Rα', expression])]). relacion([sujeto(['Patients', with, asthma, had, an]), verbo([increased]), complemento([frequency, of, 'IL-6Rα(high)', 'EM', 'CD8+', 'T', cells, in, peripheral, blood, compared, with, healthy, control, subjects])]). relacion([sujeto(['Splenocytes', from, sacrificed, mice]), verbo([stimulated]), complemento([with, 16, 'µg/ml', of, 'Der', p, were, cultured, for, 72, hours])]). relacion([sujeto(['Both', hIN, and, lmwhIN, groups, showed, significantly]), verbo([decreased]), complemento([transcripts, of, 'GATA-3,', 'IFN-γ,', 'IL-5,', and, 'RORγt', mRNA, in, their, spleen])]). relacion([sujeto(['Regarding', the, supernatant, of, splenocyte, culture]), verbo([stimulated]), complemento([with, 'Der', 'p,', compared, with, the, mIT, 'group,', there, were, significant, decreases, in, 'IL-17A/F,', 'IFN-γ,', 'IL-4,', 'IL-13,', and, 'IL-10', secretion, in, inhaled, hIN, and, lmwhIN, groups])]). relacion([sujeto(['From', this, 'balb/c', mice, 'study,', the, analyses, of, mRNA, and, cytokines, revealed, that, both, intranasal, heparin, and, lmw, heparin, treatment]), verbo([decreased]), complemento([the, expression, of, 'Th1,', 'Th2,', and, 'Th17', in, spleen])]). relacion([sujeto(['Interleukin-21', '(', 'IL-21)', reduces, allergic, symptoms, in, murine, models, and]), verbo([inhibits]), complemento(['IL-4-induced', 'IgE', secretion, by, 'B', cells])]). relacion([sujeto(['However,', whether, or, not, 'IL-21', directly, affects, 'Th2', 'cells,', which]), verbo([leads]), complemento([to, reduced, allergic, 'symptoms,', is, unclear])]). relacion([sujeto(['We']), verbo([found]), complemento([that, 'IL-21', reduced, the, number, of, differentiated, 'Th2', cells, and, these, 'Th2', cells, showed, a, diminished, 'Th2', cytokine, production])]). relacion([sujeto(['Interleukin-21']), verbo([suppressed]), complemento(['Th2', cytokine, production, of, already, polarized, 'Th2', cells, by, 'down-regulation', of, transcription, factor, 'GATA-3'])]). relacion([sujeto(['It', also]), verbo([induced]), complemento([apoptosis, of, 'Th2', cells, with, decreased, 'anti-apoptotic', factor, 'Bcl-2'])]). relacion([sujeto(['Intranasal', administration, of, 'IL-21', at, the, beginning, of, ovalbumin, '(', 'OVA)', sensitization, or, before, 'OVA', challenge]), verbo([decreased]), complemento(['Th2', cytokines, in, the, bronchoalveolar, lavage, fluid, of, 'OVA/alum-immunized', allergic, mice])]). relacion([sujeto(['In', 'addition,', the, inhibitory, effects, of, 'IL-21', on, 'Th2', effector, functions, can, also, be]), verbo([found]), complemento([in, allergic, patients])]). relacion([sujeto(['Our', results, demonstrate, that, 'IL-21']), verbo([suppresses]), complemento([the, development, of, 'Th2', cells, and, functions, of, polarized, 'Th2', cells])]). relacion([sujeto(['The', present, study, aimed, to, define, whether, 'GATA3', is]), verbo([involved]), complemento([in, the, differentiation, of, neuroblastoma, cells])]). relacion([sujeto(['The', results, demonstrated, that, 'GATA3', is, a, prognostic, marker, for, survival, in, patients, with, 'neuroblastoma,', and, that, 'high‑level', 'GATA3', expression, is]), verbo([associated]), complemento([with, increased, 'self‑renewal', and, proliferation, of, neuroblastoma, cells])]). relacion([sujeto(['Retinoic', acid, treatment]), verbo([led]), complemento([to, 'GATA3', downregulation, together, with, neuronal, 'differentiation,', suppression, of, cell, proliferation, and, inhibition, of, tumorigenecity, in, neuroblastoma, cells])]). relacion([sujeto(['These', findings]), verbo([suggest]), complemento([that, 'GATA3', is, a, key, regulator, of, neuroblastoma, 'differentiation,', and, provide, a, novel, potential, therapeutic, strategy, for, the, induction, of, neuroblastoma, differentiation])]). relacion([sujeto(['We', previously, demonstrated, that, cells, derived, from, the, mesenchymal, layer, of, the, human, amniotic, membrane, '(', 'hAMSC)', and, their, conditioned, medium, '(', 'CM-hAMSC)']), verbo([modulate]), complemento([lymphocyte, proliferation, in, a, 'dose-dependent', manner])]). relacion([sujeto(['In', order, to, understand, the, mechanisms]), verbo([involved]), complemento([in, immune, regulation, exerted, by, 'hAMSC,', we, analyzed, the, effects, of, 'CM-hAMSC', on, 'T-cell', polarization, towards, 'Th1,', 'Th2,', 'Th17,', and, 'T-regulatory', '(', 'Treg)', subsets])]). relacion([sujeto(['We', show, that, 'CM-hAMSC', equally]), verbo([suppresses]), complemento([the, proliferation, of, both, 'CD4(+)', 'T-helper', '(', 'Th)', and, 'CD8(+)', cytotoxic, 'T-lymphocytes'])]). relacion([sujeto(['We', evaluated, the, phenotype, of, 'CD4(+)', cells, in, the, 'MLR', setting, and, showed, that, 'CM-hAMSC', significantly, reduced, the, expression, of, markers]), verbo([associated]), complemento([to, the, 'Th1', '(', 'T-bet(+)CD119(+))', and, 'Th17', '(', 'RORγt(+)CD161(+))', 'populations,', while, having, no, effect, on, the, 'Th2', population, '(', 'GATA3(+)CD193(+)/GATA3(+)CD294(+)cells)'])]). relacion([sujeto(['T-cell', subset, modulation, was, substantiated, through, the, analysis, of, cytokine]), verbo([release]), complemento([for, 6, &, 'nbsp;days', during, 'co-culture', with, alloreactive, 'T-cells,', whereby, we, observed, a, decrease, in, specific, 'subset-related', 'cytokines,', such, as, a, decrease, in, 'pro-inflammatory,', 'Th1-related', '(', 'TNFα,', 'IFNγ,', 'IL-1β),', 'Th2', '(', 'IL-5,', 'IL-6),', 'Th9', '(', 'IL-9),', 'and Th17', '(', 'IL-17A,', 'IL-22)'])]). relacion([sujeto(['Furthermore,', 'CM-hAMSC', significantly]), verbo([induced]), complemento([the, 'Treg', 'compartment,', as, shown, by, an, induction, of, proliferating, 'CD4(+)FoxP3(+)', 'cells,', and, an, increase, of, 'CD25(+)FoxP3(+)', and, 'CD39(+)FoxP3(+)', 'Treg', in, the, 'CD4(+)', population])]). relacion([sujeto(['Induction', of, 'Treg', cells, was, corroborated, by, the]), verbo([increased]), complemento([secretion, of, 'TGF-β'])]). relacion([sujeto(['Taken', 'together,', these, data, strengthen, the, findings, regarding, the, immunomodulatory, properties, of, 'CM-hAMSC', derived, from, human, amniotic, membrane, 'MSC,', and, in, particular]), verbo([provide]), complemento([insights, into, their, effect, on, regulation, of, 'T', cell, polarization])]). relacion([sujeto(['We', identified, 'hsa-miR-138', '(', 'miR-138)', as, a, novel, regulator, of, invasion, and, 'epithelial-mesenchymal', transition, in, breast, cancer, 'cells,']), verbo([acting]), complemento([by, directly, targeting, the, polycomb, epigenetic, regulator, 'EZH2'])]). relacion([sujeto(['Our', results, highlight, the]), verbo([loss]), complemento([of, malignant, character, in, some, lung, micrometastatic, lesions, and, the, epigenetic, regulation, of, this, phenotype])]). relacion([sujeto(['We']), verbo([find]), complemento([that, 'BMP', signaling, is, required, for, 'HFSC', quiescence, and, to, promote, 'TAC', differentiation, along, different, lineages, as, the, hair, cycle, progresses])]). relacion([sujeto(['The', objective, of, the, present, study, was, to, assess, the, effect, of, 'alginate-encapsulated', infectious, pancreatic, necrosis, virus, antigens, in]), verbo([inducing]), complemento([the, immune, response, of, 'Atlantic', salmon, as, booster, vaccines])]). relacion([sujeto(['Compared', to, 'controls,', fish, fed, with, 'ENCAP', had, a, significant]), verbo([increase]), complemento(['(', 'p<0'])]). relacion([sujeto(['In', 'contrast,', serum, antibodies, in, the, 'UNENCAP', group]), verbo([decreased]), complemento([both, after, the, 1, st, and, 2, nd, oral, boosts])]). relacion([sujeto(['This', was]), verbo([associated]), complemento([with, significant, 'up-regulation', of, 'FOXP3,', 'TGF-β', and, 'IL-10', genes])]). relacion([sujeto(['The', expression, of, 'IgT', was, not]), verbo([induced]), complemento([in, the, hindgut, after, the, 1, st, oral, boost, but, was, significantly, 'up-regulated', following, the, 2, nd, one])]). relacion([sujeto(['IgM', mRNA, expression, on, the, other, hand, was, not, differentially]), verbo([regulated]), complemento([at, any, of, the, times, examined])]). relacion([sujeto(['Our', findings]), verbo([suggest]), complemento([that, 1, ')', 'Parenteral', prime, with, 'oil-adjuvanted', vaccines, followed, by, oral, boost, with, 'ENCAP', results, in, augmentation, of, the, systemic, immune, 'response;', 2, ')', 'Symmetrical', prime, and, boost, '(', 'mucosal)', with, 'ENCAP', results, in, augmentation, of, mucosal, immune, response, and, 3, ')', 'Symmetrical', priming, and, boosting, '(', 'mucosal)', with, soluble, antigens, results, in, the, induction, of, systemic, immune, tolerance])]). relacion([sujeto(['The', aim, of, this, study, is, to, investigate, the, expression, pattern, of, histone, deacetylase, 9, in, peripheral, blood, of, patients, with, allergic, asthma, and, its, regulatory, effect, on, the, balance, of, 'Th17/Treg', cells]), verbo([involved]), complemento([in, the, pathogenesis, of, asthma])]). relacion([sujeto(['Forty-seven', patients, with, asthma, were]), verbo([recruited]), complemento([and, assigned, to, 'intermittent,', mild, and, 'moderate-severe', group])]). relacion([sujeto(['In', 'vivo,', 'TSA', treatment, can]), verbo([inhibit]), complemento(['IL-17', but, promote, transforming, growth, 'factor-beta', production, in, the, 'BALF', of, asthma, 'mice,', and, inhibited, the, expression, of, 'Th17', cells, and, 'RORγt', mRNA, in, 'lung;', also, can, promote, 'Foxp3', mRNA, expression])]). relacion([sujeto(['HDAC9', mRNA, expression, level, was]), verbo([associated]), complemento([with, the, severity, of, disease])]). relacion([sujeto(['The', histone, deacetylase, inhibitor, 'TSA', can]), verbo([regulate]), complemento([the, balance, of, 'Th17/Treg', in, asthma, by, regulating, the, activity, of, histone, deacetylase])]). relacion([sujeto(['Enhancers']), verbo([provide]), complemento([critical, information, directing, 'cell-type-specific', transcriptional, 'programs,', regulated, by, binding, of, 'signal-dependent', transcription, factors, and, their, associated, cofactors])]). relacion([sujeto(['Here,', we]), verbo([report]), complemento([that, the, most, strongly, activated, estrogen, '(', 'E2)-responsive', enhancers, are, characterized, by, 'trans-recruitment', and, in, situ, assembly, of, a, large, 1, -, 2, 'MDa', complex, of, diverse, 'DNA-binding', transcription, factors, by, 'ERα', at, 'ERE-containing', enhancers])]). relacion([sujeto(['We', refer, to, enhancers]), verbo([recruiting]), complemento([these, factors, as, mega, transcription, 'factor-bound', in, trans, '(', 'MegaTrans)', enhancers])]). relacion([sujeto(['The', 'MegaTrans', complex, is, a, signature, of, the, most, potent, functional, enhancers, and, is]), verbo([required]), complemento([for, activation, of, enhancer, 'RNA', transcription, and, recruitment, of, 'coactivators,', including, p300, and, 'Med1'])]). relacion([sujeto(['The', 'MegaTrans', complex, 'functions,', in, 'part,', by]), verbo([recruiting]), complemento([specific, enzymatic, 'machinery,', exemplified, by, 'DNA-dependent', protein, kinase])]). relacion([sujeto(['Thus,', 'MegaTrans-containing', enhancers, represent, a, cohort, of, functional, enhancers, that]), verbo([mediate]), complemento([a, broad, and, important, transcriptional, program, and, provide, a, molecular, explanation, for, transcription, factor, clustering, and, hotspots, noted, in, the, genome])]). relacion([sujeto([5, mouse, 'brain,', we]), verbo([found]), complemento([that, 'Shh', and, its, receptor, 'Ptch1', define, two, adjacent, mutually, exclusive, gene, expression, 'domains:', 'Shh+Ptch1-', and, 'Shh-Ptch1+'])]). relacion([sujeto(['These', two, domains, are]), verbo([associated]), complemento([respectively, with, 'Foxa2', and, 'Gata3,', two, transcription, factors, that, play, key, roles, in, specifying, them])]). relacion([sujeto(['Important', 'Gata3']), verbo([targets]), complemento([include, 'Slit2', and, 'Slit3,', which, are, involved, in, the, process, of, axon, 'guidance,', as, well, as, 'Slc18a1,', 'Th', and, 'Qdpr,', which, are, associated, with, neurotransmitter, synthesis, and, release])]). relacion([sujeto(['By', 'contrast,', 'Foxa2', both, 'up-regulates', the, genes]), verbo([expressed]), complemento([in, the, 'Shh+Ptch1-', domain, and, 'down-regulates', the, genes, characteristic, of, the, 'Shh-Ptch1+', domain])]). relacion([sujeto(['Our', work]), verbo([provides]), complemento([the, first, 'genome-wide', characterization, of, the, gene, regulatory, network, involved, in, the, 'Shh', pathway, that, underlies, pattern, formation, in, the, early, mouse, brain])]). relacion([sujeto(['The', mechanisms]), verbo([involved]), complemento([in, the, regulation, of, 'CD4(+)', 'T', cell, homeostasis, by, 'galectin-1', remain, poorly, characterized])]). relacion([sujeto(['To', investigate, whether, 'galectin-1']), verbo([modulates]), complemento([the, differentiation, of, 'CD4(+)', 'T', 'cells,', the, effects, of, 'galectin-1', on, the, mRNA, expression, levels, of, 'TBX21,', 'GATA-3,', 'FOXP3', and, 'RORC', in, activated, peripheral, blood, mononuclear, cells, were, examined])]). relacion([sujeto(['In', our, 'study,', more, than, 40, '%', of, 'Brenner', tumors, had]), verbo([associated]), complemento(['Walthard', nests])]). relacion([sujeto(['The', similar, morphology, and, immunoprofile, of, 'Brenner', tumors, and, 'Walthard', nests]), verbo([suggest]), complemento([a, probable, link, between, 'Brenner', tumors, and, 'Walthard', nests])]). relacion([sujeto(['Two', additional, cases, presented, highlight, small, transitional, lesions]), verbo([involving]), complemento([the, 'ovary:', a, possible, precursor, lesion, or, the, initial, steps, of, 'Brenner', tumor, formation])]). relacion([sujeto(['Although', the, tumor]), verbo([has]), complemento([classic, morphologic, 'features,', some, cases, can, mimic, 'Müllerian', adenocarcinoma, and, be, 'misdiagnosed,', especially, those, with, significant, ductal, pattern])]). relacion([sujeto(['In', this, 'study,', we]), verbo([report]), complemento([2, cases, of, mesonephric, 'carcinosarcoma,', originally, diagnosed, as, 'Müllerian', 'carcinomas,', 1, presenting, in, the, 'vagina;', review, immunohistochemical, results, including, positivity, for, 'GATA-3,', not, previously, reported, and, comment, on, the, proposed, panel, of, 'PAX8,', 'p16,', and, estrogen, receptors, as, discriminators, of, 'Müllerian', adenocarcinoma, '(', endocervical, or, 'endometrial)', versus, mesonephric, carcinoma])]). relacion([sujeto(['Astragalus', 'membranaceus,', a, traditional, 'Chinese', 'herb,']), verbo([has]), complemento([been, used, to, improve, airway, inflammation, and, asthma])]). relacion([sujeto([membranaceus]), verbo([has]), complemento([immunotherapeutic, effects, on, 'asthma,', a, chronic, inflammatory, mucosal, disease, that, is, associated, with, excess, production, of, 'IgE,', 'eosinophilia,', 'T', helper, 2, '(', 'Th2)', 'cytokines,', and, bronchial, hyperresponsiveness])]). relacion([sujeto(['The', 'IgE', levels, in, serum, and, bronchoalveolar, lavage, fluid, showed, a, tendency, to]), verbo([decrease]), complemento([after, the, administration, of, 'A'])]). relacion([sujeto(['The', number, of, eosinophils]), verbo([decreased]), complemento([and, infiltration, of, inflammatory, cells, and, collagen, deposition, declined, in, lung, sections, after, 'A'])]). relacion([sujeto(['The', 'RNA', and, protein, levels, of, 'Th2', cytokines, and, the, ratio, of, the, 'GATA3/T-bet', mRNA, levels]), verbo([decreased]), complemento([after, 'A'])]). relacion([sujeto(['Furthermore,', the, mRNA, level, of, peroxisome, 'proliferator-activated', receptor, γ, '(', 'PPARγ),', a]), verbo([nuclear]), complemento([hormone, 'receptor,', increased, in, the, lung, tissues, of, 'A'])]). relacion([sujeto([membranaceus, water, extract]), verbo([activated]), complemento(['PPARγ', activity, in, either, human, embryonic, kidney, 293, '(', 'HEK293)', or, 'A549', cells, in, a, 'PPARγ-responsive', 'element-containing', luciferase, reporter, assay])]). relacion([sujeto([membranaceus]), verbo([has]), complemento([an, inhibitory, effect, on, airway, inflammation, in, a, murine, model, of, asthma, through, modulating, the, imbalanced, relationship, between, 'Th1', and, 'Th2', cytokines])]). relacion([sujeto(['Foxp3(+)', regulatory, 'T', '(', 'Treg)', cells, are, essential, to]), verbo([maintain]), complemento([immune, 'homeostasis,', yet, controversy, exists, about, the, stability, of, this, cell, population])]). relacion([sujeto(['In', the, periphery, of, 'Bcl6(-/-)', 'mice,']), verbo([increased]), complemento([numbers, of, 'Foxp3-negative', '\'', 'exTreg\'', cells, were, 'found,', particularly, in, the, 'CD25(+)', population])]). relacion([sujeto(['ExTreg', cells, from, 'Bcl6(-/-)', mice]), verbo([expressed]), complemento([increased, 'interleukin-17', '(', 'IL-17)', and, extremely, elevated, levels, of, 'Th2', cytokines, compared, with, 'wild-type', exTreg, cells])]). relacion([sujeto(['Although', 'Treg', cells, normally]), verbo([express]), complemento([only, low, levels, of, 'cytokines,', 'Treg', cells, from, 'Bcl6(-/-)', mice, secreted, higher, levels, of, 'IL-4,', 'IL-5,', 'IL-13', and, 'IL-17', than, 'wild-type', conventional, 'T', cells])]). relacion([sujeto(['Bcl6(Foxp3-/-)', mice, do, not, develop, inflammatory, 'disease,', indicating, a, requirement, for, 'non-Treg', cells, for, inflammation, in, 'Bcl6(-/-)', 'mice,', and]), verbo([have]), complemento([normal, numbers, of, exTreg, cells])]). relacion([sujeto(['We']), verbo([induced]), complemento(['Th2-type', allergic, airway, inflammation, in, 'Bcl6(Foxp3-/-)', 'mice,', and, found, that, while, exTreg, cytokine, expression, was, 'normal,', 'Bcl6-deficient', 'Treg', cells, expressed, higher, levels, of, the, 'Th2-specific', regulator, 'Gata3', than, 'Bcl6(+)', 'Treg', cells])]). relacion([sujeto(['Bcl6(Foxp3-/-)', mice, had]), verbo([increased]), complemento([numbers, of, 'Th2', cells, after, induction, of, airway, inflammation, and, increased, 'T', cells, in, the, bronchoalveolar, lavage, fluid])]). relacion([sujeto(['Naïve', 'CD4(+)', 'T', cells, are]), verbo([activated]), complemento([and, differentiate, to, distinct, lineages, of, 'T', helper, '(', 'Th)', 'cells,', which, are, involved, in, physiological, and, pathological, processes, by, obtaining, the, potential, to, produce, different, 'lineage-specific', cytokines, that, mediate, adaptive, immunity])]). relacion([sujeto(['In', the, past, 'decade,', our, knowledge, of, 'Th', cells]), verbo([has]), complemento([been, significantly, expanded, with, the, findings, of, new, lineages])]). relacion([sujeto(['Given', the, multiple, function, of, 'IL-9,', 'Th9', cells]), verbo([participate]), complemento([in, the, lesion, of, many, 'diseases,', such, as, allergic, 'inflammation,', 'tumor,', and, parasitosis])]). relacion([sujeto(['In', this, 'chapter,', we, will, focus, on, the, 'cytokines,', 'co-stimulatory', 'factors,', and, transcriptional, signaling, 'pathways,', which]), verbo([regulate]), complemento(['Th9', cells, development, as, well, as, 'stability,', 'plasticity,', and, the, multiple, roles, of, 'Th9', cells, in, vivo])]). relacion([sujeto(['CD4+', 'T', helper, cells]), verbo([regulate]), complemento([appropriate, cellular, and, humoral, immune, responses, to, a, wide, range, of, pathogens, and, get, involved, in, many, diseases, progress])]). relacion([sujeto(['With', the, new, sequence, 'technologies,', the]), verbo([finding]), complemento([of, key, gene, mutation, in, 'Th1/Th2', cells, has, been, proved, to, be, related, to, human, diseases])]). relacion([sujeto(['The', distinctive, differentiated, states, of, the, 'CD4+', 'T', helper, cells, are, determined, by, the, set, of, transcription, factors, and, the, genes]), verbo([transcribed]), complemento([by, the, transcription, factors])]). relacion([sujeto(['IL-12', and, 'IFN-γ', make, 'Naive', 'CD4+', 'T', cells, highly]), verbo([express]), complemento(['T-bet', and, 'STAT4', and, differentiate, to, 'TH1', 'cells,', while, 'IL-4', make, 'Naive', 'CD4+', 'T', cells, highly, express, 'STAT6', and, 'GATA3', and, differentiated, to, 'TH2', cells])]). relacion([sujeto(['There', are, some, successful, 'strategies,', which, are, revealed, to]), verbo([targeting]), complemento([chemokines, and, their, 'receptors,', that, have, been, developed, to, treat, human, 'immune-related', diseases])]). relacion([sujeto(['ASH2L', is, a, component, of, 'MLL', complexes, that]), verbo([confer]), complemento(['H3K4', trimethylation])]). relacion([sujeto(['We']), verbo([found]), complemento([that, increased, 'ASH2L', 'expression,', which, can, result, from, gene, 'amplification,', is, often, correlated, with, increased, 'ERα', expression, in, both, breast, cancer, cell, lines, and, primary, breast, cancers])]). relacion([sujeto(['Forced', expression, of, 'ASH2L']), verbo([induced]), complemento(['ERα', expression, in, mammary, epithelial, 'cells,', whereas, depletion, of, 'ASH2L', suppressed, 'ERα', expression, in, breast, cancer, cells])]). relacion([sujeto(['To', understand, the, mechanism, by, which, 'ASH2L']), verbo([regulates]), complemento(['ERα', 'expression,', we, identified, 'GATA3', as, the, binding, protein, of, 'ASH2L'])]). relacion([sujeto(['ASH2L', was]), verbo([recruited]), complemento([to, the, enhancer, of, the, 'ERα', gene, through, 'GATA3', to, promote, 'ERα', transcription])]). relacion([sujeto(['This', study, established, that, 'ASH2L']), verbo([enhances]), complemento(['ERα', expression, as, a, coactivator, of, 'GATA3', in, breast, cancers])]). relacion([sujeto(['Salivary', gland, adenocarcinomas]), verbo([have]), complemento([not, been, evaluated, for, potential, aberrant, caspase, 14, expression])]). relacion([sujeto(['Caspase', 14, is, not]), verbo([expressed]), complemento([in, normal, salivary, 'glands,', while, in, a, subfraction, of, carcinomas, '(', 32, '%', ')', an, aberrant, expression, was, found])]). relacion([sujeto(['Caspase', 14, staining, was, not]), verbo([associated]), complemento([with, tumour, 'dedifferentiation,', 'GATA3', expression, or, amplification, of, gene, locus, 19, p13])]). relacion([sujeto(['In', 'summary,', aberrant, expression, of, caspase, 14, can, be]), verbo([found]), complemento([in, a, subfraction, of, salivary, gland, carcinomas, but, could, not, be, used, as, a, biomarker, for, a, specific, carcinoma, subtype, of, the, salivary, gland])]). relacion([sujeto(['The', disease, is]), verbo([caused]), complemento([by, 'Orientia', 'tsutsugamushi,', an, obligately, intracellular, 'Gram-negative', bacterium])]). relacion([sujeto(['We']), verbo([found]), complemento([no, activation, or, even, reduction, in, 'base-line', expression, for, multiple, molecules, '(', 'IL-7,', 'IL-4,', 'IL-13,', 'GATA3,', 'ROR-γt,', and, 'CXCL12)', at, 2, ',', 6, and, 10, days, 'post-infection'])]). relacion([sujeto(['The', elevated, angiopoietin, '(', 'Ang)-2', expression, and, 'Ang-2/Ang-1', ratios]), verbo([suggested]), complemento([excessive, inflammation, and, the, loss, of, endothelial, integrity])]). relacion([sujeto(['This', is, the, first]), verbo([report]), complemento([of, selective, alterations, in, a, panel, of, immune, regulators, during, early, 'O'])]). relacion([sujeto(['Our', findings, shed, new, light, on, the, pathogenic, mechanisms]), verbo([associated]), complemento([with, severe, scrub, typhus, and, suggest, potential, targets, for, therapeutic, investigation])]). relacion([sujeto(['The', prevalence, of, asthma, in, girls]), verbo([increases]), complemento([after, puberty])]). relacion([sujeto(['Previous', studies]), verbo([have]), complemento([detected, associations, between, sex, hormones, and, 'asthma,', as, well, as, between, sex, hormones, and, 'T', helper, 2, '(', 'Th2)', 'asthma-typical', immune, responses])]). relacion([sujeto(['Therefore,', we, hypothesized, that, exogenous, or, endogenous, sex, hormone, exposure, '(', represented, by, oral, contraceptive, pill, '(', 'OCP)', use, and, early, 'menarche,', 'respectively)', are]), verbo([associated]), complemento([with, 'DNA', methylation, '(', 'DNA-M)', of, the, 'Th2', transcription, factor, 'gene,', 'GATA3,', in, turn, affecting, the, risk, of, asthma, in, 'girls,', possibly, in, interaction, with, genetic, variants])]). relacion([sujeto(['In', a, second, 'stage,', we, determined, whether, these, 'CpG', sites]), verbo([interact]), complemento([with, genetic, variants, in, 'GATA3', to, explain, the, risk, of, asthma])]). relacion([sujeto(['The', interaction, between, 'OCP', use, and, 'SNP', rs1269486, was]), verbo([found]), complemento([to, be, associated, with, the, methylation, level, of, cg17124583, '(', 'P', =, 0.002, ',', false, discovery, rate, '(', 'FDR)', adjusted, 'P', =, 0.04, ')'])]). relacion([sujeto(['In', stage, 2, ',', we]), verbo([found]), complemento([that, cg17124583, modified, the, association, of, 'SNP', rs422628, with, asthma, risk, at, the, age, of, 18, &, 'nbsp;years', '(', 'P', =, 0.006, ',', 'FDR', adjusted, 'P', =, 0.04, ')'])]). relacion([sujeto(['Subjects', with, genotype, 'AG', showed, an]), verbo([increase]), complemento([in, average, risk, ratio, '(', 'RR)', from, 0.31, '(', 95, '%', 'CI:', 0.1, to, 0.8, ')', to, 11.65, '(', 95, '%', 'CI:', 1.71, to, 79.5, ')', when, methylation, level, increased, from, 0.02, to, 0.12, ',', relative, to, genotype, 'AA'])]). relacion([sujeto(['A', 'two-stage', model, consisting, of, genetic, variants, in, the, 'GATA3', 'gene,', 'OCP', 'use,', age, at, 'menarche,', and, 'DNA-M', may, explain, how, sex, hormones, in, women, can]), verbo([increase]), complemento([the, asthma, prevalence, after, puberty])]). relacion([sujeto(['The', establishment, and, maintenance, of, mammary, epithelial, cell, identity, depends, on, the, activity, of, a, group, of, 'proteins,', collectively, called, maintenance, 'proteins,', that]), verbo([act]), complemento([as, epigenetic, regulators, of, gene, transcription, through, 'DNA', 'methylation,', histone, 'modification,', and, chromatin, remodeling])]). relacion([sujeto(['Increasing', evidence, indicates, that, dysregulation, of, these, crucial, proteins, may, disrupt, epithelial, cell, integrity, and]), verbo([trigger]), complemento([breast, tumor, initiation])]). relacion([sujeto(['Therefore,', we, explored, in, silico, the, expression, pattern, of, a, panel, of, 369, genes, known, to, be]), verbo([involved]), complemento([in, the, establishment, and, maintenance, of, epithelial, cell, identity, and, mammary, gland, remodeling, in, cell, subpopulations, isolated, from, normal, human, mammary, tissue, and, selectively, enriched, in, their, content, of, bipotent, 'progenitors,', committed, luminal, 'progenitors,', and, differentiated, myoepithelial, or, differentiated, luminal, cells])]). relacion([sujeto(['The', results, indicated, 'that,', compared, to, bipotent, 'cells,', differentiated, myoepithelial, and, luminal, subpopulations, were, both, characterized, by, the, differential, expression, of, 4, genes]), verbo([involved]), complemento([in, cell, identity, 'maintenance:', 'CBX6', and, 'PCGF2,', encoding, proteins, belonging, to, the, 'Polycomb', 'group,', and, 'SMARCD3', and, 'SMARCE1,', encoding, proteins, belonging, to, the, 'Trithorax', group])]). relacion([sujeto(['In', addition, to, these, common, 'genes,', the, myoepithelial, phenotype, was]), verbo([associated]), complemento([with, the, differential, expression, of, 'HDAC1,', which, encodes, histone, deacetylase, 1, ',', whereas, the, luminal, phenotype, was, associated, with, the, differential, expression, of, 'SMARCA4', and, 'HAT1,', which, encode, a, 'Trithorax', protein, and, histone, acetylase, 1, ',', respectively])]). relacion([sujeto(['The', luminal, compartment, was, further, characterized, by, the, overexpression, of, 'ALDH1A3', and, 'GATA3,', and, the, 'down-regulation', of, 'NOTCH4', and, 'CCNB1,', with, the, latter]), verbo([suggesting]), complemento([a, block, in, cell, cycle, progression, at, the, 'G2', phase])]). relacion([sujeto(['In', 'contrast,', myoepithelial, differentiation, was]), verbo([associated]), complemento([with, the, overexpression, of, 'MYC', and, the, 'down-regulation', of, 'CCNE1,', with, the, latter, suggesting, a, block, in, cell, cycle, progression, at, the, 'G1', phase])]). relacion([sujeto(['Acute', rejection, is, still, a, major]), verbo([cause]), complemento([of, graft, dysfunction, and, would, jeopardize, 'recipients\'', 'post-transplantation', survival])]). relacion([sujeto(['Current', studies, demonstrate, that, 'Galectin-9', '(', 'Gal-9)', is]), verbo([associated]), complemento([with, 'down-regulation', of, 'pro-inflammatory', 'cytokines,', 'thus,', possesses, a, negative, immune, regulatory, role])]). relacion([sujeto(['Increasing', gestational, age, was]), verbo([associated]), complemento([with, a, decrease, in, 'extent/intensity', of, expression, in, 'non-neoplastic', cytotrophoblast, and, 'syncytiotrophoblast,', whereas, intermediate, trophoblast, maintained, diffuse, and, strong, expression, from, early, to, late, gestation, '(', 'P<0'])]). relacion([sujeto(['We', conclude, that, 'GATA-3', is, frequently]), verbo([expressed]), complemento([in, normal, and, lesional, trophoblastic, tissues])]). relacion([sujeto(['It', is, also, differentially]), verbo([expressed]), complemento([in, intermediate, trophoblast, and, 'cytotrophoblast/syncytiotrophoblast,', which, varies, according, to, time, during, pregnancy])]). relacion([sujeto(['This', study, expands, the, spectrum, of, neoplasms, known, to]), verbo([express]), complemento(['GATA-3'])]). relacion([sujeto(['Thus,', recognition, of, expression, in, trophoblastic, tumors, is, 'important,', because, it, can, present, a, diagnostic, pitfall, in, the, assessment, of, suspected, metastatic, bladder, or, breast, carcinomas]), verbo([involving]), complemento([the, gynecologic, tract])]). relacion([sujeto(['The', opportunistic, fungal, pathogen, 'Cryptococcus', neoformans]), verbo([causes]), complemento([lung, inflammation, and, fatal, meningitis, in, immunocompromised, patients])]). relacion([sujeto(['We', show, that, the, number, of, 'CD4(+)', 'FoxP3(+)', 'Treg', cells, in, the, lung]), verbo([increases]), complemento([significantly, within, the, first, 4, weeks, after, intranasal, infection, of, 'BALB/c', 'wild-type', mice])]). relacion([sujeto(['In', 'Treg', 'cell-depleted', 'mice,', stronger, pulmonary, allergic, inflammation, with]), verbo([enhanced]), complemento([mucus, production, and, pronounced, 'eosinophilia,', increased, 'IgE', 'production,', and, elevated, fungal, lung, burden, were, found])]). relacion([sujeto(['In', 'contrast,', only, a, mild]), verbo([increase]), complemento([in, the, 'Th1-associated', immune, response, unrelated, to, the, fungal, infection, was, observed])]). relacion([sujeto(['In', 'conclusion,', the, data, demonstrate, that, during, fungal, infection, pulmonary, 'Treg', cells, are]), verbo([induced]), complemento([and, preferentially, suppress, 'Th2', cells, thereby, mediating, enhanced, fungal, control])]). relacion([sujeto(['These']), verbo([targets]), complemento([could, mediate, two, distinct, roles, played, by, 'GATA-3', in, lineage, 'commitment,', as, revealed, by, removing, 'wild-type', or, 'GATA-3-deficient', early, 'T', lineage, cells, from, environmental, 'Notch', signals])]). relacion([sujeto(['GATA-3', worked, as, a, potent, repressor, of, 'B', cell, potential, even, at, low, expression, 'levels,', so, that, only, full, deletion, of, 'GATA-3', enabled, 'pro-T', cells, to]), verbo([reveal]), complemento(['B', cell, potential])]). relacion([sujeto(['The', ability, of, 'GATA-3', to, block, 'B', cell, development, did, not]), verbo([require]), complemento(['T', lineage, commitment, factor, 'Bcl11b'])]). relacion([sujeto(['In', prethymic, multipotent, 'precursors,', 'however,', titration, of, 'GATA-3', activity, using, 'tamoxifen-inducible', 'GATA-3', showed, that, 'GATA-3']), verbo([inhibits]), complemento(['B', and, myeloid, developmental, alternatives, at, different, threshold, doses])]). relacion([sujeto(['Furthermore,', differential, impacts, of, a, 'GATA-3', obligate, repressor, construct, imply, that, 'B', and, myeloid, development, are]), verbo([inhibited]), complemento([through, distinct, transcriptional, mechanisms])]). relacion([sujeto(['The', prevalence, of, black, gram, '(', 'Vigna', 'mungo)']), verbo([induced]), complemento([allergic, reactions, are, reported, from, several, parts, of, the, world, including, 'Asia', and, 'Australia'])]). relacion([sujeto(['But,', a, thorough, exploration, of, the, allergic, reactions]), verbo([induced]), complemento([by, black, gram, proteins, is, still, lacking])]). relacion([sujeto(['Therefore,', efforts]), verbo([have]), complemento([been, made, to, explore, black, gram, allergy, using, in, vivo, and, in, vitro, approaches])]). relacion([sujeto(['Moreover,', the, expression, of, 'Th2', cytokine, transcripts, and, 'GATA-3/T-bet', ratio, was]), verbo([found]), complemento([enhanced, in, the, treated, group])]). relacion([sujeto(['In', vitro, studies, on, 'RBL-2H3', 'cells,showed']), verbo([increased]), complemento([release, of, 'β-hexosaminidase', '(', p, &, 'lt;', 0.05, ')', ',', histamine, '(', p, &, 'lt;', 0.05, ')', ',', cysteinyl, leukotriene, '(', 'p<0'])]). relacion([sujeto(['Further,', 8.5, '%', of, screened, patients, were]), verbo([found]), complemento([allergic, to, black, gram, and, concomitant, sensitization, with, other, allergens, has, shown, the, possibility, of, further, enhancement, in, allergenic, problem])]). relacion([sujeto(['Conclusively,', the, present, study]), verbo([suggested]), complemento([that, black, gram, consumption, may, be, responsible, for, inducing, immediate, type, of, allergic, sensitization, in, susceptible, subjects])]). relacion([sujeto(['The', compound, also, significantly]), verbo([inhibited]), complemento([the, synthesis, of, 'GATA-3-encoding', mRNA, and, protein, in, addition, to, increasing, the, synthesis, of, 'T-bet-encoding', mRNA, and, protein, in, both, lung, tissues, and, 'CD4+', 'T', cells])]). relacion([sujeto(['Our', findings, indicate, that, 'AST', treatment]), verbo([inhibits]), complemento(['ovalbumin-induced', airway, inflammation, by, modulating, the, key, master, switches, 'GATA-3', and, 'T-bet,', which, results, in, committing, 'T', helper, cells, to, a, 'Th1', phenotype])]). relacion([sujeto(['Recent', studies, demonstrated, that, microRNAs, '(', 'miRNAs)', are]), verbo([involved]), complemento([in, development, of, 'CHD'])]). relacion([sujeto(['This', study, was, to, characterize, the, expression, of, miRNAs, that, might, be]), verbo([involved]), complemento([in, the, development, or, reflect, the, consequences, of, 'VSD'])]). relacion([sujeto([3]), verbo([target]), complemento([gene, databases, were, employed, to, predict, the, target, genes, of, differentially, expressed, miRNAs])]). relacion([sujeto([36, differentially]), verbo([expressed]), complemento([miRNAs, were, found, in, the, patients, with, 'VSD', and, the, 'VSD-free', controls])]). relacion([sujeto(['Gene', ontology, analysis, indicated, that, the, top]), verbo([target]), complemento([genes, were, mainly, related, to, cardiac, right, ventricle, morphogenesis])]). relacion([sujeto(['NOTCH1,', 'HAND1,', 'ZFPM2,', and, 'GATA3', were, predicted, as]), verbo([targets]), complemento([of, 'hsa-let-7e-5p,', 'hsa-miR-222-3p', and, 'hsa-miR-433'])]). relacion([sujeto(['We']), verbo([report]), complemento([for, the, first, time, the, circulating, miRNA, profile, for, patients, with, 'VSD', and, showed, that, 7, miRNAs, were, downregulated, and, 1, upregulated, when, matched, to, 'VSD-free', controls])]). relacion([sujeto(['Analysis', revealed]), verbo([target]), complemento([genes, involved, in, cardiac, development, were, probably, regulated, by, these, miRNAs])]). relacion([sujeto(['Extracellular', calcium]), verbo([participates]), complemento([in, several, key, physiological, 'functions,', such, as, control, of, blood, 'coagulation,', bone, calcification, or, muscle, contraction])]). relacion([sujeto(['Calcium', homeostasis, in, humans, is]), verbo([regulated]), complemento([in, part, by, genetic, 'factors,', as, illustrated, by, rare, monogenic, diseases, characterized, by, hypo, or, hypercalcaemia])]). relacion([sujeto(['Serum', calcium, levels, are, tightly]), verbo([regulated]), complemento([by, two, main, hormonal, 'systems,', i])]). relacion([sujeto(['CYP24A1,', 'CASR,', 'GATA3;', 'CYP2R1)', between, genes]), verbo([involved]), complemento([in, rare, monogenic, diseases, and, genes, located, within, loci, identified, in, 'GWAS', suggests, a, genetic, and, phenotypic, continuum, between, monogenic, diseases, of, calcium, homeostasis, and, slight, disturbances, of, calcium, homeostasis, in, the, general, population])]). relacion([sujeto(['These', findings, will, likely]), verbo([provide]), complemento([new, insight, into, the, complex, mechanisms, involved, in, calcium, homeostasis, and, hopefully, lead, to, novel, preventive, and, therapeutic, approaches])]). relacion([sujeto(['Breast', cancer, expression, profiling]), verbo([has]), complemento([been, used, for, determining, biomarkers])]). relacion([sujeto(['Expression', of, 'TPD52,', 'GATA3', and, 'KRT18', was]), verbo([increased]), complemento([in, 'KRT19', expressing, patients])]). relacion([sujeto(['Furthermore,', 'KRT19', expression, was]), verbo([associated]), complemento([with, 'ER', 'up-regulation', and, 'Luminal', 'B', gene, 'signatures,', as, well, as, a, constitutive, 'RAF1', signaling, pathway])]). relacion([sujeto(['Taken', 'together,', our, results]), verbo([suggest]), complemento([that, 'KRT19', expression, can, be, used, as, a, prognostic, marker])]). relacion([sujeto(['T-regulatory', '(', 'Treg)', cells, are, important, to, immune, 'homeostasis,', and, 'Treg', cell, deficiency, or, dysfunction]), verbo([leads]), complemento([to, autoimmune, disease])]). relacion([sujeto(['A', 'histone/protein', acetyltransferase, '(', 'HAT),', 'p300,', was, recently]), verbo([found]), complemento([to, be, important, for, 'Treg', function, and, 'stability,', but, further, insights, into, the, mechanisms, by, which, p300, or, other, 'HATs', affect, 'Treg', biology, are, needed])]). relacion([sujeto(['Thus,', while, mice, with, 'Treg-specific', deletion, of, 'CBP', or, p300, developed, minimal, autoimmune, 'disease,', the, combined, deletion, of, 'CBP', and, p300]), verbo([led]), complemento([to, fatal, autoimmunity, by, 3, to, 4, weeks, of, age])]). relacion([sujeto(['The', effects, of, 'CBP', and, p300, deletion, on, 'Treg', development, are, dose, dependent, and]), verbo([involve]), complemento([multiple, mechanisms])]). relacion([sujeto(['CBP', and, p300, cooperate, with, several, key, 'Treg', transcription, factors, that]), verbo([act]), complemento([on, the, 'Foxp3', promoter, to, promote, 'Foxp3', production])]). relacion([sujeto(['CBP', and, p300, also]), verbo([act]), complemento([on, the, 'Foxp3', conserved, noncoding, sequence, 2, '(', 'CNS2)', region, to, maintain, 'Treg', stability, in, inflammatory, environments, by, regulating, pCREB, function, and, 'GATA3', 'expression,', respectively])]). relacion([sujeto(['Lastly,', 'CBP', and, p300]), verbo([regulate]), complemento([the, epigenetic, status, and, function, of, 'Foxp3'])]). relacion([sujeto(['Our', findings]), verbo([provide]), complemento([insights, into, how, 'HATs', orchestrate, multiple, aspects, of, 'Treg', development, and, function, and, identify, overlapping, but, also, discrete, activities, for, p300, and, 'CBP', in, control, of, 'Treg', cells])]). relacion([sujeto(['Although', the, 'T', 'cell-rich', myocarditis, is, known, to, play, a, pathogenetic, 'role,', the, relative, contribution, of, each, of, the, functional, 'T', cell, subsets]), verbo([has]), complemento([never, been, thoroughly, investigated])]). relacion([sujeto(['We', therefore, assessed, gene, expression, of, cytokines, and, transcription, factors]), verbo([involved]), complemento([in, differentiation, and, effector, function, of, each, functional, 'T', cell, subset, '(', 'TH1/TH2/TH17/Treg)', in, 'CCC,', 'NIC,', and, heart, donor, myocardial, samples])]). relacion([sujeto(['Quantitative', 'PCR', showed, markedly, upregulated, expression, of, 'IFN-γ', and, transcription, factor, 'T-bet,', and, minor]), verbo([increases]), complemento([of, 'GATA-3;', 'FoxP3', and, 'CTLA-4;', 'IL-17', and, 'IL-18', in, 'CCC', as, compared, with, 'NIC', samples])]). relacion([sujeto(['Conversely,', cytokines]), verbo([expressed]), complemento([by, 'TH2', cells, '(', 'IL-4,', 'IL-5,', and, 'IL-13)', or, associated, with, 'Treg', '(', 'TGF-β', and, 'IL-10)', were, not, upregulated, in, 'CCC', myocardium])]). relacion([sujeto(['Results', are, consistent, with, a, strong, local, 'TH1-mediated', response, in, most, 'samples,', possibly]), verbo([associated]), complemento([with, pathological, myocardial, 'remodeling,', and, a, proportionally, smaller, 'FoxP3(+)CTLA4(+)', 'Treg', cell, 'population,', which, is, unable, to, completely, curb, 'IFN-γ', production, in, 'CCC', 'myocardium,', therefore, fueling, inflammation])]). relacion([sujeto(['Often']), verbo([associated]), complemento([with, estrogen, receptor, '(', 'ER)', 'signaling,', 'GATA3', expression, has, been, reported, in, 'ER-negative', breast, 'cancers,', but, systematic, evaluation, of, 'GATA3', expression, in, a, large, set, of, 'triple-negative', breast, cancers, '(', 'TNBC)', is, lacking])]). relacion([sujeto(['GATA3-L', is, more, sensitive, for, 'TNBC', than, 'GATA3-H,', and, an, immunopanel, of, 'GATA3-L,', 'MGB,', and, 'GCDFP15']), verbo([provides]), complemento([optimal, diagnostic, sensitivity, for, 'TNBC'])]). relacion([sujeto(['WYRE', significantly, reduced, viability, of, both, cell, lines, and]), verbo([enhanced]), complemento([mRNA, content, of, 'GATA3', in, a, 'concentration-dependent', 'manner;', 'however,', 'DNMT', mRNAs, '(', 'DNMT1,', 3, 'A,', 3, 'B)', were, found, to, increase, significantly, only, in, 'MDA-MB-231', cells])]). relacion([sujeto(['No', alterations, in, any, of, the, 'TET', mRNAs, were]), verbo([found]), complemento([in, 'MCF-7', cells])]). relacion([sujeto(['RIP140', is, a, transcriptional, coregulator]), verbo([involved]), complemento([in, energy, 'homeostasis,', 'ovulation,', and, mammary, gland, development])]). relacion([sujeto(['Although', conclusive, evidence, is, 'lacking,']), verbo([reports]), complemento([have, implicated, a, role, for, 'RIP140', in, breast, cancer])]). relacion([sujeto(['Using', 'ChIP-seq', 'analysis,', we, demonstrate, that, 'RIP140', shares, more, than, 80, '%', of, its]), verbo([binding]), complemento([sites, with, 'ERα,', colocalizing, with, its, interaction, partners, 'FOXA1,', 'GATA3,', 'p300,', 'CBP,', and, p160, family, members, at, 'H3K4me1-demarcated', enhancer, regions])]). relacion([sujeto(['RIP140', is]), verbo([required]), complemento([for, 'ERα-complex', 'formation,', 'ERα-mediated', gene, 'expression,', and, 'ERα-dependent', breast, cancer, cell, proliferation])]). relacion([sujeto(['Cumulatively,', our, data]), verbo([suggest]), complemento([that, 'RIP140', plays, an, important, role, in, 'ERα-mediated', transcriptional, regulation, in, breast, cancer, and, response, to, tamoxifen, treatment])]). relacion([sujeto(['Here', we]), verbo([find]), complemento([that, enhanced, expression, of, 'Grail,', an, 'E3', ubiquitin, 'ligase,', in, 'Th2', cells, depends, on, interleukin, '(', 'IL)-4-signalling', 'components,', signal, transducer, and, activator, of, transcription, 6, '(', 'Stat6)', and, 'Gata3,', that, bind, to, and, transactivate, the, 'Grail', promoter])]). relacion([sujeto(['Grail', deficiency, in, 'T', cells]), verbo([leads]), complemento([to, increased, expression, of, 'Th2', effector, cytokines, in, vitro, and, in, vivo, and, 'Grail-deficient', mice, are, more, susceptible, to, allergic, asthma])]). relacion([sujeto(['Mechanistically,', the]), verbo([enhanced]), complemento([effector, function, of, 'Grail-deficient', 'Th2', cells, is, mediated, by, increased, expression, of, 'Stat6', and, 'IL-4', receptor, 'α-chain'])]). relacion([sujeto(['Grail']), verbo([interacts]), complemento([with, 'Stat6', and, targets, it, for, ubiquitination, and, degradation])]). relacion([sujeto(['In', the, present, 'study,', we, showed, the, level, of, 'MDSCs', in, 'PBMC', and, 'Arg1', in, plasma, were, significantly, elevated, in, 'ECA', 'patients,', and, the]), verbo([increased]), complemento([ratio, of, 'MDSC', in, 'PBMC', was, closely, related, to, the, expression, of, 'CD163', in, cancer, tissues])]). relacion([sujeto(['In', 'addition,', the, 'ECA', patients, exhibited, remarkable]), verbo([increases]), complemento([in, the, mRNA, levels, of, 'IL-4', and, 'GATA3,', as, well, as, the, protein, levels, of, 'IL-13', and, 'IL-6,', but, 'IFN-γ', and, 'IL-12', in, peripheral, blood, were, decreased])]). relacion([sujeto(['Our', data, indicate, that, the]), verbo([increased]), complemento(['Th2', cytokines, are, associated, with, 'MDSCs', and, 'M2', macrophages, 'polarization,', and, foster, the, infiltration, of, 'CD163+M2', macrophages, in, cancer, 'tissues,', which, promote, the, formation, of, immunosuppressive, microenvironment, in, 'ECA', patients])]). relacion([sujeto(['Neuroinflammation']), verbo([has]), complemento([been, shown, to, contribute, to, the, development, of, neuropathic, pain])]). relacion([sujeto(['We']), verbo([have]), complemento([previously, demonstrated, that, lumbar, spinal, 'cord-infiltrating', 'CD4(+)', 'T', lymphocytes, contribute, to, the, maintenance, of, mechanical, hypersensitivity, in, spinal, nerve, 'L5', transection, '(', 'L5Tx),', a, murine, model, of, neuropathic, pain])]). relacion([sujeto(['Here,', we, further, examined, the, phenotype, of, the, 'CD4(+)', 'T', lymphocytes]), verbo([involved]), complemento([in, the, maintenance, of, neuropathic, 'pain-like', behavior, via, intracellular, flow, cytometric, analysis, and, explored, potential, interactions, between, infiltrating, 'CD4(+)', 'T', lymphocytes, and, spinal, cord, glial, cells])]). relacion([sujeto(['This']), verbo([suggests]), complemento([that, the, infiltrating, 'CD4(+)', 'T', lymphocytes, expressed, a, 'pro-inflammatory', type, 1, phenotype, '(', 'Th1)'])]). relacion([sujeto(['In', 'addition,', spinal, cord, astrocytic, 'activation,', represented, by, glial, fibillary, acidic, protein, '(', 'GFAP)', 'expression,', was, significantly, lower, in, 'CD4', 'KO', mice, compared, to, wild, type, '(', 'WT)', mice, at, day, 14, 'post-L5Tx,']), verbo([suggesting]), complemento([the, involvement, of, astrocytes, in, the, pronociceptive, effects, mediated, by, infiltrating, 'CD4(+)', 'T', lymphocytes])]). relacion([sujeto(['In', 'all,', these, data, indicate, that, the, maintenance, of, 'L5Tx-induced', neuropathic, pain, is, mostly]), verbo([mediated]), complemento([by, 'Th1', cells, in, a, 'CD154-independent', manner, via, a, mechanism, that, could, involve, multiple, 'Th1', cytokines, and, astrocytic, activation])]). relacion([sujeto(['Here,', we, show, that, two, members, of, the, 'EphA', subfamily, of, receptor, tyrosine, 'kinases,', 'EphA4', and, 'EphA7,', are, specifically]), verbo([expressed]), complemento([in, the, mesenchyme, surrounding, the, caudal, 'ND', and, the, 'cloaca,', and, that, 'Epha4(-/-);Epha7(+/-)', and, 'Epha4(-/-);Epha7(-/-)', '(', 'DKO)', mice, display, distal, ureter, malformations, including, 'ureterocele,', blind, and, ectopically, ending, ureters, with, associated, 'hydroureter,', megaureter, and, hydronephrosis])]). relacion([sujeto(['Expression', of, 'Gata3', and, 'Lhx1', and, their, downstream]), verbo([target]), complemento(['Ret', is, severely, reduced, in, the, caudal, 'ND'])]). relacion([sujeto(['Conditional', deletion, of, ephrin, 'B2', from, the, 'ND', largely, phenocopies, these, 'changes,']), verbo([suggesting]), complemento([that, 'EphA4/EphA7', from, the, pericloacal, mesenchyme, signal, via, ephrin, 'B2', to, mediate, 'ND', insertion])]). relacion([sujeto(['We', assessed, the, effect, of, microbiota, compositional, changes]), verbo([induced]), complemento([by, a, diet, enriched, in, 5, '%', acidic, oligosaccharides, derived, from, pectin, '(', 'pAOS)', on, the, immune, response, and, outcome, of, chronic, pulmonary, 'P'])]). relacion([sujeto([pAOS]), verbo([promoted]), complemento(['Th1', polarization, by, increasing, interferon, γ, 'release,', upregulating, 't-bet', gene, 'expression,', decreasing, interleukin, 4, 'secretion,', and, downregulating, gata3, gene, expression])]). relacion([sujeto([pAOS, also, sustained, the]), verbo([release]), complemento([of, keratinocyte, 'chemoattractant,', recruited, polynuclear, leukocytes, and, 'macrophages,', stimulated, 'M1', macrophage, activation, and, interleukin, 10, 'release,', and, decreased, tumor, necrosis, factor, α, release, in, the, lung])]). relacion([sujeto(['These', effects]), verbo([led]), complemento([to, increased, bacterial, clearance, after, the, first, and, second, 'P'])]). relacion([sujeto([pAOS, modified, the, intestinal, microbiota, by]), verbo([stimulating]), complemento([the, growth, of, species, involved, in, immunity, 'development,', such, as, 'Bifidobacterium', 'species,', 'Sutturella', 'wadsworthia,', and, 'Clostridium', cluster, 'XIVa', 'organisms,', and, at, the, same, time, increased, the, production, of, butyrate, and, propionate])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, pAOS, may, have, beneficial, effects, by, limiting, the, number, and, severity, of, pulmonary, exacerbations, in, patients, chronically, infected, with, 'P'])]). relacion([sujeto(['Eight', genes, '(', 'AIRE,', 'CASR,', 'CLDN16,', 'GATA3,', 'GCM2,', 'PTH,', 'TBCE,', and, 'TRPM6)', are, known, to, be, responsible, genes]), verbo([associated]), complemento([with, 'HP;', 'however,', no, previous, study, has, screened, the, eight, responsible, genes, comprehensively, in, 'HP', patients])]). relacion([sujeto(['Mutations', and, genomic, rearrangements]), verbo([involving]), complemento([the, eight, genes, were, screened, by, targeted, 'next-generation', sequencing, '(', 'NGS)'])]). relacion([sujeto(['Functional', studies, of, 'R367Tfs*-', and, 'T370M-GCM2', demonstrated, a, reduction, of]), verbo([target]), complemento([gene, transactivation, in, both])]). relacion([sujeto(['The', pseudoangiosarcomatous, pattern]), verbo([has]), complemento([been, described, mostly, in, cutaneous, and, some, visceral, squamous, cell, carcinomas, and, is, unique, for, its, striking, morphologic, resemblance, to, angiosarcoma])]). relacion([sujeto(['The', tumor, was, commonly]), verbo([associated]), complemento([with, a, dense, collagenous, 'matrix,', often, surrounding, the, lytic, nests])]). relacion([sujeto(['The', pseudoangiosarcomatous, urothelial, carcinomas, were, all, '(', 7, /, 7, ')', diffusely, 'CK7', 'positive,', most, '(', 6, /, 7, ')', were, 'GATA3', 'positive,', and, none, '(', 0, /, 7, ')']), verbo([expressed]), complemento(['vascular-associated', markers])]). relacion([sujeto(['There', was, no, evidence, to]), verbo([suggest]), complemento([that, apoptosis, '(', by, 'TUNEL', assay, and, cleaved, 'caspase-3', 'immunostaining)', or, loss, of, the, adhesion, molecules, 'CD138', and, 'e-cadherin', were, possible, causes, for, the, tumor, cell, discohesion, and, breakdown])]). relacion([sujeto(['In', 'conclusion,', we, present, an, unusual, morphology, of, bladder, carcinoma, that]), verbo([has]), complemento([a, striking, resemblance, to, a, malignant, vasoformative, tumor])]). relacion([sujeto(['Our', series, showed, that, bladder, pseudoangiosarcomatous, carcinoma, morphology, is]), verbo([associated]), complemento([with, a, higher, tumor, stage, at, 'cystectomy,', commonly, admixed, with, other, aggressive, carcinoma, variant, 'morphologies,', and, portend, a, poorer, outcome])]). relacion([sujeto(['Gut', microbiota]), verbo([mediated]), complemento(['low-grade', inflammation, is, involved, in, the, onset, of, type, 2, diabetes, '(', 'T2DM)'])]). relacion([sujeto(['Hyperglycemia', was, favorably]), verbo([suppressed]), complemento([by, 'L'])]). relacion([sujeto(['This', chloride, ion]), verbo([loss]), complemento([was, significantly, prevented, by, 'L'])]). relacion([sujeto(['This', study, was, aimed, to, compare, the, expressions, of, specific, transcription, factors, of, 'CD4(+)', 'T', cell, subset, '(', 'T-bet,', 'GATA-3,', 'RORγt', and, 'FoxP3', 'mRNA)', in, peripheral, blood, of, patients, with, aplastic, 'anemia(AA),', myelodysplastic, 'syndrome(MDS),', and, acute, myeloid, 'leukemia(AML),', and, investigate, their, immune, status, and, 'pathogenesis,', so, as, to]), verbo([provide]), complemento([experimental, basis, for, the, choice, of, clinical, treatment])]). relacion([sujeto(['Emerging', therapies, for, sensorineural, hearing]), verbo([loss]), complemento([include, replacing, damaged, auditory, neurons, '(', 'ANs)', using, stem, cells])]). relacion([sujeto(['As', human]), verbo([induced]), complemento([pluripotent, stem, cells, '(', 'hiPSCs)', can, be, obtained, directly, from, the, 'patient,', they, offer, an, opportunity, to, generate, 'patient-matched', neurons, for, transplantation])]). relacion([sujeto(['Immunocytochemistry', and, 'qRT-PCR', were, used, to, analyze, the, expression, of, key, markers]), verbo([involved]), complemento([in, 'AN', development, at, defined, time, points, of, differentiation])]). relacion([sujeto(['The', 'hiPSC-', and, 'hESC-derived', neurosensory, progenitors]), verbo([expressed]), complemento([the, dorsal, hindbrain, marker, '(', 'PAX7),', otic, placodal, marker, '(', 'PAX2),', proneurosensory, marker, '(', 'SOX2),', ganglion, neuronal, markers, '(', 'NEUROD1,', 'BRN3A,', 'ISLET1,', 'ßIII-tubulin,', 'Neurofilament', kDa, 160, ')', ',', and, sensory, 'AN', markers, '(', 'GATA3', and, 'VGLUT1)', over, the, time, course, examined])]). relacion([sujeto(['Furthermore,', the, neurons, generated, from, this, assay, were]), verbo([found]), complemento([to, be, electrically, active])]). relacion([sujeto(['Overall,', these, findings, indicate, that, this, neural, assay, was, capable, of, differentiating, hiPSCs, toward, a, neurosensory, lineage, but, emphasize, the, need, for, improving, the, consistency, in, the, differentiation, of, hiPSCs, into, the]), verbo([required]), complemento([lineages])]). relacion([sujeto(['Studies', in, 'zebrafish,', 'Xenopus,', and, chick]), verbo([reveal]), complemento([that, the, 'PPE', is, specified, together, with, other, ectodermal, territories, '(', 'epidermis,', neural, 'crest,', and, neural, 'plate)', during, early, embryogenesis])]). relacion([sujeto(['At', neural, plate, 'stages,', the, 'PPE', is, then]), verbo([induced]), complemento([in, the, 'non-neural', competence, territory, by, signals, from, the, adjacent, neural, plate, and, mesoderm, including, 'FGF,', 'BMP', 'inhibitors,', and, 'Wnt', inhibitors])]). relacion([sujeto(['Subsequently,', signals, from, more, localized, signaling, centers]), verbo([induce]), complemento([restricted, expression, domains, of, various, transcription, factors, within, the, 'PPE,', which, specify, multiplacodal, areas, and, ultimately, individual, placodes])]). relacion([sujeto(['The', author]), verbo([has]), complemento([declared, no, conflicts, of, interest, for, this, article])]). relacion([sujeto(['In', the, respiratory, 'mucosa,', interleukin, '(', 'IL)-33,']), verbo([has]), complemento([been, shown, to, enhance, 'T', helper, 2, '(', 'TH2)-type', responses, through, the, master, regulatory, gene, 'GATA-3'])]). relacion([sujeto(['Mesenteric', lymph, node, '(', 'MesLN)', 'T', cells, were, isolated, from, 'PAC', 'IL-10', '(', -, /, -, ')', mice, and]), verbo([stimulated]), complemento([with, 'IL-33'])]). relacion([sujeto(['MesLN', 'T', cells]), verbo([stimulated]), complemento([with, 'IL-33', had, increased, 'GATA-3', 'expression,', and, showed, an, 'IL-33', 'dose-dependent', increase, in, secreted, 'TH2-type', 'cytokines,', whereas, this, effect, was, abolished, by, blocking, 'IL-33', signaling])]). relacion([sujeto(['The', 'non-TH2-type', cytokine, 'IL-17', was, upregulated, by, 'IL-33', but, in, a, 'T', cell, receptor, dependent, 'manner,', as, opposed, to, 'TH2-type', 'cytokines,', which]), verbo([required]), complemento([only, 'IL-33', stimulation])]). relacion([sujeto(['The', study, demonstrates, that, intestinal, 'IL-33', is, capable, of]), verbo([inducing]), complemento(['GATA-3', in, mucosal, 'T', 'cells,', and, suggests, that, 'IL-33', is, a, key, mediator, of, pathological, 'TH2', and, 'non-TH2-type', responses, in, intestinal, inflammation])]). relacion([sujeto(['The', identification, of, 'DC-derived', signals, orchestrating, activation, of, 'Th1', and, 'Th17', immune, responses]), verbo([has]), complemento([advanced, our, understanding, on, how, these, inflammatory, responses, develop])]). relacion([sujeto(['However,', whether, specific, signals, delivered, by, 'DCs', also]), verbo([participate]), complemento([in, the, regulation, of, 'Th2', immune, responses, remains, largely, unknown])]). relacion([sujeto(['In', this, 'study,', we, show, that, administration, of, 'antigen-loaded,', 'IL-6-deficient', 'DCs', to, naïve, mice]), verbo([induced]), complemento([an, exacerbated, 'Th2', 'response,', characterized, by, the, differentiation, of, 'GATA-3-expressing', 'T', lymphocytes, secreting, high, levels, of, 'IL-4,', 'IL-5,', and, 'IL-13'])]). relacion([sujeto(['This']), verbo([finding]), complemento([was, confirmed, in, 'vitro,', where, exogenously, added, 'IL-6', was, found, to, limit, 'IL-4-induced', 'Th2-cell', differentiation])]). relacion([sujeto([iNKT, cells, were]), verbo([required]), complemento([for, optimal, 'Th2-cell', differentiation, in, vivo, although, their, activation, occurred, independently, of, 'IL-6', secretion, by, the, 'BMDCs'])]). relacion([sujeto(['GATA3', as, a, diagnostic, marker, of, metastatic, breast, carcinoma, in, cytology, specimens]), verbo([has]), complemento([not, been, fully, established])]). relacion([sujeto(['On', qualitative, univariate, 'analysis,', 'GATA3', was, statistically]), verbo([associated]), complemento([with, 'ER', '(', 'P', =, 0.0001, ')', ',', and, 'PR', '(', 'P', =, 0.0468, ')'])]). relacion([sujeto(['GATA3', intensity, was, statistically]), verbo([associated]), complemento([with, 'ER', '(', 'P', '≤', 0.0001, ')', ',', 'PR', '(', 'P', =, 0.0157, ')', ',', 'Her2', '(', 'P', =, 0.0256, ')', ',', and, cancer, category, '(', 'P', =, 0.0127, ')'])]). relacion([sujeto(['GATA3', staining, was, statistically]), verbo([associated]), complemento([with, 'ER', '(', 'P', '≤', 0.0001, ')', ',', 'PR', '(', 'P', =, 0.016, ')', ',', 'Her2', '(', 'P', =, 0.0451, ')', ',', and, cancer, category, '(', 'P', =, 0.0002, ')'])]). relacion([sujeto(['To', observe, the, effect, of, needle, pricking, therapy, on, the, expression, of, thymic, stromal, lymphopoietin, '(', 'TSLP)', 'protein,', 'T-box']), verbo([expressed]), complemento([in, 'T', 'cells(T-bet)mRNA', and, 'GATA-binding', 'protein-3', '(', 'GATA', 3, ')', mRNA, in, the, lung, tissue, of, mice, with, 'asthma,', so, as, to, explore, its, mechanism, underlying, improvement, of, asthma])]). relacion([sujeto(['Compared', with, the, control, 'group,', the, expression, levels, of, 'GATA-3', mRNA, and, 'TSLP', protein, of, the, lung, tissue, in, the, model, group, were, significantly]), verbo([increased]), complemento(['(', 'P', &, 'lt;', 0.01, ')', ',', whereas, that, of, 'T-bet', mRNA, was, remarkably, decreased, '(', 'P', &, 'lt;', 0.05, ')'])]). relacion([sujeto(['Needle', pricking, therapy, can]), verbo([regulate]), complemento([the, expression, of, pulmonary, 'TSLP', protein, and, 'GATA', 3, and, 'T-bet', genes, in, mice, with, 'asthma,', which, may, contribute, to, its, effect, in, improving, pulmonary, pathological, changes, of, asthma, mice])]). relacion([sujeto(['These', tumors]), verbo([release]), complemento([specific, molecules, into, the, environment, that, trigger, characteristic, responses, into, the, circulatory, cells])]). relacion([sujeto(['In', this, study, we, investigated, the, expression, pattern, of, 84, genes, known, to, be]), verbo([involved]), complemento([in, breast, cancer, signaling, in, the, peripheral, blood, of, breast, cancer, patients, with, 'ER-,', 'PR-', primary, tumors])]). relacion([sujeto(['Transcriptional', analysis, revealed, 15, genes, to, be, differentially]), verbo([expressed]), complemento([between, the, two, groups, highlighting, that, 'Her2', signaling, in, primary, tumors, could, be, associated, with, specific, blood, gene, expression])]). relacion([sujeto(['We']), verbo([found]), complemento(['CCNA1', to, be, 'up-regulated,', while, 'ERBB2,', 'RASSF1,', 'CDH1,', 'MKI67,', 'GATA3,', 'GLI1,', 'SFN,', 'PTGS2,', 'JUN,', 'NOTCH1,', 'CTNNB1,', 'KRT8,', 'SRC,', and, 'HIC1', genes, were, 'down-regulated', in, the, blood, of, triple, negative, breast, cancer, patients, compared, to, 'Her2+', cohort])]). relacion([sujeto(['IPA', network, analysis, predicts, that, the, identified, genes, are, interconnected, and]), verbo([regulate]), complemento([each, other])]). relacion([sujeto(['These', genes, code, for, cell, cycle, 'regulators,', cell, adhesion, 'molecules,', transcription, factors, or, signal, transducers, that]), verbo([modulate]), complemento([immune, 'signaling,', several, genes, being, also, associated, with, cancer, progression, and, treatment, response])]). relacion([sujeto(['This', study, was, conducted, to, explore, the, 'anti-asthma', effects, of, synthetic, salidroside, on, cytokines, and, airway, inflammation, of, asthma]), verbo([induced]), complemento([by, diisocyanate, '(', 'TDI)', in, mice])]). relacion([sujeto(['After', the, 'experiment,', histological, studies, were, evaluated, by, the, hematoxylin, and, eosin, 'staining,', the, bronchoalveolar, lavage, fluid, '(', 'BALF)', and, blood, were, collected, from, the, 'animals,', and, the, composition, of, the]), verbo([induced]), complemento([inflammatory, 'cells,', and, the, concentrations, of, certain, cytokines, '(', 'IL-4,', 'INF-γ)', were, evaluated])]). relacion([sujeto(['Our', study, demonstrated, that, salidroside]), verbo([inhibited]), complemento(['TDI-induced', increases, in, eosinophil, 'count;', 'IL-4', and, 'INF-γ', were, recovered])]). relacion([sujeto(['Histological', studies, demonstrated, that, salidroside, substantially]), verbo([inhibited]), complemento(['TDI-induced', eosinophilia, in, lung, tissue])]). relacion([sujeto(['These', findings]), verbo([suggest]), complemento([that, salidroside, may, effectively, ameliorate, the, progression, of, asthma, and, could, be, used, as, a, therapy, for, patients, with, allergic, asthma, by, regulating, 'GATA3/T-bet', balance])]). relacion([sujeto(['GATA3', is, a, transcription, factor, that, is]), verbo([involved]), complemento([in, the, embryonic, development, of, the, parathyroid, glands, and, in, adult, parathyroid, cell, proliferation])]). relacion([sujeto(['Immunoreactivity', for, 'GATA3', was]), verbo([nuclear]), complemento([and, was, demonstrated, in, all, 10, hyperplastic, parathyroid, 'glands,', 22, parathyroid, 'adenomas,', and, 6, parathyroid, 'carcinomas;', 'whereas,', all, thyroid, 'tumors,', renal, cell, 'carcinomas,', thymic, epithelial, 'tumors,', and, carcinoid, tumors, investigated, for, comparison, purposes, were, negative, for, this, marker])]). relacion([sujeto(['We', identified, key, components]), verbo([involved]), complemento([in, 'PPR', differentiation])]). relacion([sujeto(['The', 'mesoderm/marginal', 'Wnts', at, the, early, gastrula, stage]), verbo([trigger]), complemento([differentiation, by, allowing, the, adjacent, 'NNE', border, cells, to, start, adopting, caudal, 'PPR', 'fates;', 'otherwise,', the, development, of, caudal, 'PPR', identity, is, hindered, due, to, the, persistent, presence, of, gata3, mRNA])]). relacion([sujeto(['The', caudal, 'PPR', fate, dominates, when, foxi1, expression, is]), verbo([enhanced]), complemento([at, the, late, gastrula, 'stage,', and, depleting, 'Foxi1', after, 6, hours, postfertilization, '(', 'hpf)', reduces, the, 'otic-epibranchial', placodal, domain])]). relacion([sujeto(['In', establishing, 'PPR', 'polarity,', both, 'Gata3', and, 'Foxi1']), verbo([inhibit]), complemento(['Bmp', 'signaling,', whereas, 'Foxi1', 'inhibits,', but, 'Gata3', 'enhances,', 'Fgf', sensitivity, of, the, 'PPR', cells])]). relacion([sujeto(['Our', study]), verbo([reveals]), complemento([that, in, 'zebrafish,', '(', 1, ')', the, 'PPR', at, the, shield, stage, may, enter, a, developmental, state, when, the, 'PPR', cells, preferentially, adopt, a, particular, placodal, fate, and, '(', 2, ')', a, network, of, genetically, linked, 'factors,', including, 'Wnt/beta-catenin,', 'Fgfr,', 'Bmp,', 'Gata3,', and, 'Foxi1,', direct, the, process, of, 'PPR', differentiation])]). relacion([sujeto(['Increased', presence, of, 'TH2/TH17', cells, was]), verbo([associated]), complemento([with, increased, 'IL-17', production, in, lavage, fluid])]). relacion([sujeto(['They']), verbo([expressed]), complemento([higher, levels, of, 'mitogen-activated', 'protein-extracellular', 'signal-regulated', kinase, kinase, 1, ',', a, molecule, that, induces, glucocorticoid, resistance])]). relacion([sujeto(['Asthma', is]), verbo([associated]), complemento([with, a, higher, frequency, of, 'dual-positive', 'TH2/TH17', cells, in, 'BAL', fluid])]). relacion([sujeto(['Th2', memory, lymphocytes]), verbo([have]), complemento([imprinted, their, 'Il4', genes, epigenetically, for, expression, in, dependence, of, 'T', cell, receptor, restimulation])]). relacion([sujeto(['However,', in, a, given, 'restimulation,', not, all, 'Th', cells, with, a, memory, for, 'IL-4', expression]), verbo([express]), complemento(['IL-4'])]). relacion([sujeto(['Here,', we, show, that, in]), verbo([reactivated]), complemento(['Th2', 'cells,', the, transcription, factors, 'NFATc2,', 'NF-kB', 'p65,', 'c-Maf,', 'p300,', 'Brg1,', 'STAT6,', and, 'GATA-3', assemble, at, the, 'Il4', promoter, in, 'Th2', cells, expressing, 'IL-4', but, not, in, 'Th2', cells, not, expressing, it])]). relacion([sujeto(['Because', 'NFATc2', translocation, into, the, nucleus, occurs, in, an, 'all-or-none', 'fashion,', dependent, on, complete, dephosphorylation, by, 'calcineurin,', 'NFATc2', controls, the, frequencies, of, cells, reexpressing, 'Il4,']), verbo([translates]), complemento([analog, differences, in, 'T', cell, receptor, stimulation, into, a, digital, decision, for, 'Il4', 'reexpression,', and, instructs, all, reexpressing, cells, to, express, the, same, amount, of, 'IL-4'])]). relacion([sujeto(['This', 'analog-to-digital', conversion, may, be, critical, for, the, immune, system, to]), verbo([respond]), complemento([to, low, concentrations, of, antigens])]). relacion([sujeto(['In', this, 'study,', we]), verbo([found]), complemento([that, 'cyanidin-3-glucoside', chloride, '(', 'C3G),', an, anthocyanin, suppressed, 'IL-4', and, 'IL-13', produced, in, activated, 'EL-4', 'T', cells, but, not, 'Th1', cytokines, including, 'IL-2,', 'interferon-γ,', or, 'IL-12'])]). relacion([sujeto(['IL-4', and, 'IL-13', mRNA, levels, and, luciferase, activation, in, cells, transiently, transfected, with, 'IL-4', and, 'IL-13', promoter, reporter, plasmids, were, significantly]), verbo([inhibited]), complemento([by, 'C3G,', suggesting, that, suppression, might, 'be,', at, least, in, 'part,', regulated, at, the, transcriptional, level])]). relacion([sujeto(['Data', from, western, blot, and, reverse, 'transcription-polymerase', chain, reaction, analyses, of, transcription, factors]), verbo([involved]), complemento([in, cytokine, expression, suggested, that, expression, of, 'GATA-3,', but, not, 'T-bet,', was, downregulated, in, the, nucleus, by, 'C3G'])]). relacion([sujeto(['Taken', 'together,', our, data, indicate, that, 'C3G', may]), verbo([has]), complemento([potential, as, an, 'anti-allergic', agent, suppressing, 'Th2', activation, by, downregulating, 'Th2', cytokines, and, the, 'GATA3', transcription, factor, in, allergies])]). relacion([sujeto(['With', regard, to, markers, for, urothelial, 'differentiation,', the, committee]), verbo([found]), complemento([that, there, is, no, ideal, marker, or, established, panel, to, confirm, urothelial, differentiation])]). relacion([sujeto(['With', regard, to, the, role, of, 'IHC', in, the, distinction, of, reactive, atypia, from, urothelial, carcinoma, in, 'situ,', the, committee, recommended, that, morphology, remains, the, gold, standard, in, this, differential, diagnosis, and, 'that,', at, 'best,', the, 'IHC', panel, of, 'CK20/p53/CD44(s)']), verbo([has]), complemento([potential, utility, but, is, variably, used, and, has, limitations])]). relacion([sujeto(['IHC']), verbo([has]), complemento([no, role, in, the, distinction, of, dysplasia, versus, carcinoma, in, situ, and, in, the, grading, of, papillary, urothelial, carcinoma])]). relacion([sujeto(['IHC', may]), verbo([have]), complemento([a, limited, but, distinct, role, in, staging, of, bladder, cancer])]). relacion([sujeto(['The', early, differentiation, of, 'T', helper, '(', 'Th)', cells, is, a, tightly, controlled, and, finely, balanced, 'process,', which]), verbo([involves]), complemento([several, factors, including, 'cytokines,', transcription, factors, and, 'co-stimulatory', molecules])]). relacion([sujeto(['Recent', studies]), verbo([have]), complemento([shown, that, in, addition, to, the, regulation, of, 'apoptosis,', caspase, activity, is, also, needed, for, 'Th', cell, proliferation, and, activation, and, it, might, play, a, role, in, 'Th', cell, differentiation])]). relacion([sujeto(['The', isoforms, of, the, cellular, 'FLICE', inhibitory, protein, '(', 'c-FLIP)', are, regulators, of, 'CASPASE-8', activity, and, the, short, 'isoform,', 'c-FLIPS,']), verbo([has]), complemento([been, shown, to, be, 'up-regulated', by, 'IL-4,', the, 'Th2', driving, cytokine])]). relacion([sujeto(['In', this, 'work,', we]), verbo([have]), complemento([studied, the, expression, and, functional, role, of, three, 'c-FLIP', isoforms, during, the, early, 'Th', cell, differentiation])]). relacion([sujeto(['Only', two, of, the, 'isoforms,', 'c-FLIPS', and, 'c-FLIPL,', were, detected, at, the, protein, level, although, 'c-FLIPR', was]), verbo([expressed]), complemento([at, the, mRNA, level])]). relacion([sujeto(['The', knockdown, of, 'c-FLIPL']), verbo([led]), complemento([to, enhanced, 'Th1', differentiation, and, elevated, 'IL-4', production, by, 'Th2', 'cells,', whereas, the, knockdown, of, 'c-FLIPS', diminished, 'GATA3', expression, and, 'IL-4', production, by, 'Th2', cells])]). relacion([sujeto(['In', 'summary,', our, results]), verbo([provide]), complemento([new, insight, into, the, role, of, 'c-FLIP', proteins, in, the, early, differentiation, of, human, 'Th', cells])]). relacion([sujeto(['New', immunohistochemical, '(', 'IHC)', markers, of, urothelial, carcinoma, '(', 'UCa)', and, prostatic, adenocarcinoma, '(', 'PCa)']), verbo([have]), complemento([emerged, in, recent, 'years,', yet, comparative, studies, to, establish, markers, remain, lacking])]). relacion([sujeto(['Hosts', are, likely, to]), verbo([respond]), complemento([to, parasitic, infections, by, a, combination, of, resistance, '(', expulsion, of, 'pathogens)', and, tolerance, '(', active, mitigation, of, 'pathology)'])]). relacion([sujeto(['In', comparison, to, immature, 'males,', mature, males, resisted, infection, less, and, instead]), verbo([increased]), complemento([investment, in, body, condition, in, response, to, accumulating, 'burdens,', but, at, the, expense, of, reduced, reproductive, effort])]). relacion([sujeto(['Time', series, data, for, individual, animals]), verbo([suggested]), complemento([that, macroparasite, infections, gave, rise, to, increased, expression, of, 'Gata3,', which, gave, rise, to, improved, body, condition, and, enhanced, survival, as, hosts, aged])]). relacion([sujeto(['These', findings]), verbo([provide]), complemento([a, clear, and, unexpected, insight, into, tolerance, responses, '(', and, their, life, history, 'sequelae)', in, a, natural, vertebrate, population])]). relacion([sujeto(['The', demonstration, that, such, responses, '(', potentially]), verbo([promoting]), complemento([parasite, 'transmission)', can, move, from, resistance, to, tolerance, through, the, course, of, an, 'individual\'s', lifetime, emphasises, the, need, to, incorporate, them, into, our, understanding, of, the, dynamics, and, risk, of, infection, in, the, natural, environment])]). relacion([sujeto(['To', observe, the, change, of, regulatory, 'T', 'cells(Tregs),', fork, 'head-like', transcription, factor, 3, '(', 'Foxp3),', 'T', box]), verbo([expressed]), complemento([in, 'T', cells, '(', 'T-bet)', and, 'GATA', binding, protein, 3, '(', 'GATA3)', in, rat, models, of, chronic, obstructive, pulmonary, disease, '(', 'COPD)'])]). relacion([sujeto(['Compared', with, the, control, 'group,', the, model, group, had, more, serious, inflammation, in, lung, 'tissues,']), verbo([expressed]), complemento([the, higher, levels, of, 'IFN-γ', in, serum, and, 'BALF', '(', 'P<0'])]). relacion([sujeto(['Our', results, establish, the, feasibility, and, utility, of, enhancer, profiling, in, 'well-defined', populations, of, specialized, cell, types]), verbo([involved]), complemento([in, disease, pathogenesis])]). relacion([sujeto(['In', a, previous, 'study,', we]), verbo([reported]), complemento([that, intrathecal, injection, of, mesenchymal, stem, cells, '(', 'MSCs)', slowed, disease, progression, in, 'G93A', mutant, superoxide, dismutase1, transgenic, mice])]). relacion([sujeto(['In', this, 'study,', we]), verbo([found]), complemento([that, intrathecal, 'MSC', administration, vastly, increased, the, infiltration, of, peripheral, immune, cells, into, the, spinal, cord, of, 'Amyotrophic', lateral, sclerosis, '(', 'ALS)', mice, '(', 'G93A', mutant, superoxide, dismutase1, 'transgenic)'])]). relacion([sujeto(['Based', on, a, 'fluorescence-activated', cell, sorting, 'analysis,', we]), verbo([found]), complemento([that, 'co-culture', with, 'MSCs', increased, the, 'Treg', /, total, 'T-lymphocyte', ratio, in, the, 'PBMCs', from, both, groups, according, to, the, 'co-culture', duration])]). relacion([sujeto(['Co-culture', of, 'PBMCs', with, 'MSCs', for, 24, &, 'nbsp;h']), verbo([led]), complemento([to, elevated, mRNA, levels, of, 'IFN-γ', and, 'IL-10', in, the, 'PBMCs', from, both, groups])]). relacion([sujeto(['Furthermore,', we]), verbo([found]), complemento([that, the, increased, mRNA, level, of, indoleamine, 2, ',', 3, -, dioxygenase, '(', 'IDO)', in, the, 'co-cultured', 'MSCs', was, correlated, with, the, increase, in, 'Treg', induction])]). relacion([sujeto(['These', findings, of, 'Treg', induction, and]), verbo([increased]), complemento(['anti-inflammatory', cytokine, expression, in, 'co-cultured', 'ALS', 'PBMCs', provide, indirect, evidence, that, 'MSCs', may, play, a, role, in, the, immunomodulation, of, inflammatory, responses, when, 'MSC', therapy, is, targeted, to, 'ALS', patients])]). relacion([sujeto(['We', propose, the, following, mechanism, for, the, effect, of, mesenchymal, stem, cells, '(', 'MSCs)', administered, intrathecally, in, amyotrophic, lateral, sclerosis, '(', 'ALS):', 'MSCs']), verbo([increase]), complemento([infiltration, of, peripheral, immune, cells, into, 'CNS', and, skew, the, infiltrated, immune, cells, toward, regulatory, 'T', lymphocytes, '(', 'Treg', ')', and, 'Th2', lymphocytes])]). relacion([sujeto(['A', series, of, immunomodulatory, mechanism]), verbo([provides]), complemento([a, new, strategy, for, 'ALS', treatment])]). relacion([sujeto(['There']), verbo([have]), complemento([been, limited, studies, on, the, 'UC', markers, 'GATA-binding', protein, 3, '(', 'GATA3),', 'p63,', and, p40, in, 'MPUC'])]). relacion([sujeto([p63, expression, was, strong, and, diffuse, in, all, 'LGUC,', significantly]), verbo([decreased]), complemento([in, high, stage, and, 'HGUC,', and, virtually, absent, in, 'MPUC'])]). relacion([sujeto([p40, expression, was]), verbo([decreased]), complemento([in, 'HGUC', and, markedly, decreased, in, 'MPUC', relative, to, 'LGUC'])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, loss, of, p63, expression, in, a, 'UC', appears, to, be, associated, with, adverse, 'features--including', cases, with, micropapillary, differentiation])]). relacion([sujeto(['Decreased', 'GATA3', expression, was, seen, frequently, in, 'high-grade', and, 'high-pathologic', stage, '(', '≥pT2)', tumors, but, was]), verbo([retained]), complemento([in, 'MPUC', cases])]). relacion([sujeto(['The', findings, of]), verbo([retained]), complemento(['GATA3', expression, in, 'MPUC,', which, often, shows, a, loss, of, expression, of, other, urothelial, markers, such, as, 'p63,', may, be, helpful, for, determining, the, origin, of, micropapillary, carcinoma, of, unknown, primary])]). relacion([sujeto(['Despite', the, importance, of, 5, -, 'HT1A', as, a, major]), verbo([target]), complemento([for, the, action, of, several, 'anxiolytics/antidepressant', 'drugs,', little, is, known, about, its, regulation, in, central, serotonin, '(', 5, -, 'hydroxytryptamine,', 5, -, 'HT)', neurons])]). relacion([sujeto(['We']), verbo([report]), complemento([that, expression, of, 5, -, 'HT1A', and, the, transcription, factor, 'Pet1', was, impaired, in, the, rostral, raphe, nuclei, of, mice, lacking, tryptophan, hydroxylase, 2, '(', 'Tph2)', after, birth])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([a, causal, relationship, between, 5, -, 'HT1A', and, 'Pet1,', and, reveal, a, potential, mechanism, by, which, 5, -, 'HT1A-Pet1', autoregulatory, loop, is, maintained, by, 5, -, 'HT', in, a, 'spatiotemporal-specific', manner, during, postnatal, development])]). relacion([sujeto(['TiO2', nanoparticles, '(', 'NPs)', are, used, in, the, food, industry, but]), verbo([have]), complemento([potential, toxic, effects, in, humans, and, animals])]). relacion([sujeto(['However,', 'TiO2', 'NPs']), verbo([have]), complemento([been, demonstrated, to, impair, liver, function, and, cause, liver, inflammation, in, animal, 'models,', which, may, be, associated, with, activation, of, 'Th2', 'factor-mediated', pathways])]). relacion([sujeto(['We', investigated, whether, 'TiO2', 'NPs']), verbo([activate]), complemento([the, 'Th2', 'factor-mediated', signaling, pathway, under, 'TiO2', 'NP-induced', hepatic, toxicity])]). relacion([sujeto(['The', results, showed, that, mice, exhibited, an, accumulation, of, titanium, in, the, 'liver,', which, in, turn]), verbo([led]), complemento([to, reductions, in, body, 'weight,', increases, in, liver, 'indices,', liver, 'dysfunction,', infiltration, of, inflammatory, 'cells,', and, hepatocyte, apoptosis, or, necrosis])]). relacion([sujeto(['Furthermore,', hepatic, inflammation, was, accompanied, by]), verbo([increased]), complemento(['(', 0.67, ±, 0.09, -, to, 2.14, ±, 0.19, -, 'fold)', 'IL-4', expression, and, 'up-regulation', of, its, target, genes, including, 'IL-5', '(', 0.1, ±, 0.06, -, to, 0.69, ±, 0.12, -, 'fold),', 'IL-12', '(', 0.08, ±, 0.03, -, to, 0.83, ±, 0.21, -, 'fold),', 'IFN-γ', '(', 0.17, ±, 0.09, -, to, 0.87, ±, 0.15, -, 'fold),', 'GATA3', '(', 0.05, ±, 0.02, -, to, 1.29, ±, 0.18, -, 'fold),', 'GATA4', '(', 0.04, ±, 0.01, -, to, 0.87, ±, 0.13, -, 'fold),', 'T-bet', '(', 0.3, ±, 0.06, -, to, 0.93, ±, 0.15, -, 'fold),', 'RORγt', '(', 0.32, ±, 0.11, -, to, 1.67, ±, 0.17, -, 'fold),', 'STAt3', '(', 0.16, ±, 0.06, -, to, 2.14, ±, 0.23, -, 'fold),', 'STAT6', '(', 0.2, ±, 0.05, -, to, 0.63, ±, 0.12, -, 'fold),', eotaxin, '(', 0.53, ±, 0.13, -, to, 1.49, ±, 0.21, -, 'fold),', 'MCP-1', '(', 0.5, ±, 0.11, -, to, 0.74, ±, 0.18, -, 'fold),', and, 'MIP-2', '(', 0.27, ±, 0.07, -, to, 0.71, ±, 0.18, -, 'fold)', and, significant, 'down-regulation', of, its, target, gene, 'STAT1', '(', -, 0.15, ±, 0.05, to, -, 0.81, ±, 0.11, -, 'fold)'])]). relacion([sujeto(['Taken', 'together,', the, alteration, of, 'Th2', factor, expression, may, be]), verbo([involved]), complemento([in, the, control, of, hepatic, inflammation, induced, by, chronic, 'TiO2', 'NP', toxicity])]). relacion([sujeto(['These', ligaments]), verbo([have]), complemento([been, documented, in, a, wide, variety, of, mammalian, 'species,', including, 'humans,', but, their, composition, and, ontogeny, is, unexplored])]). relacion([sujeto(['The', gastric, ligaments, coexpress, the, transcription, factors, 'Gata3,', 'Nkx2-5,', and, 'Sox9,', and, germline]), verbo([loss]), complemento([of, 'Gata3', or, conditional, deletion, of, 'Nkx2-5', abrogates, 'Sox9', expression, and, impairs, gastric, ligament, smooth, muscle, 'development;', similar, phenotypes, were, previously, seen, in, the, 'OLM'])]). relacion([sujeto(['In', accord, with, this, molecular, contiguity, between, the, 'OLM', and, gastric, 'ligaments,', 'three-dimensional', image, reconstruction, highlights, physical, contiguity, between, these, smooth, muscle, 'structures,']), verbo([suggesting]), complemento([that, they, may, work, together, as, a, unit, to, control, flexure, of, the, pyloric, 'region,', a, function, similar, to, the, ligament, of, 'Treitz', at, the, duodenojejunal, junction])]). relacion([sujeto(['These', findings, may]), verbo([have]), complemento([implications, for, our, understanding, of, normal, pyloric, sphincter, 'function,', as, well, as, the, common, human, congenital, pathology, idiopathic, hypertrophic, pyloric, stenosis])]). relacion([sujeto(['Currently', it, is, not, known, what, kind, of, immune, responses]), verbo([lead]), complemento([to, successful, control, and, clearance, of, 'Mycobacterium', tuberculosis])]). relacion([sujeto(['We']), verbo([have]), complemento([used, the, 'Mycobacterium', marinum, infection, model, in, the, adult, zebrafish, and, taken, advantage, of, heterogeneity, of, zebrafish, population, to, dissect, the, characteristics, of, adaptive, immune, 'responses,', some, of, which, are, associated, with, 'well-controlled', latency, or, bacterial, clearance, while, others, with, progressive, infection])]). relacion([sujeto(['It', was, discovered, that, a, high, total, 'T', cell, level, was, usually]), verbo([associated]), complemento([with, lower, bacterial, loads, alongside, with, a, 'T', helper, 2, '(', 'Th2)-type', gene, expression, signature])]). relacion([sujeto(['Characteristic', 'gata3/tbx21']), verbo([has]), complemento([potential, as, a, biomarker, for, the, status, of, mycobacterial, disease])]). relacion([sujeto(['Differentiation', of, naïve, 'CD4(+)', 'T', cells, into, effector, '(', 'Th1,', 'Th2,', and, 'Th17)', and]), verbo([induced]), complemento([regulatory, '(', 'iTreg)', 'T', cells, requires, 'lineage-specifying', transcription, factors, and, epigenetic, modifications, that, allow, appropriate, repression, or, activation, of, gene, transcription])]). relacion([sujeto(['The', epigenetic, silencing, of, cytokine, genes, is]), verbo([associated]), complemento([with, the, repressive, 'H3K27', trimethylation, 'mark,', mediated, by, the, 'Ezh2', or, 'Ezh1', methyltransferase, components, of, the, polycomb, repressive, complex, 2, '(', 'PRC2)'])]). relacion([sujeto(['In', 'addition,', deficiency, of, 'Ezh2', accelerated, effector, 'Th', cell, death, via, death, 'receptor-mediated', extrinsic, and, intrinsic, apoptotic, 'pathways,', confirmed, in, vivo, for, 'Ezh2-null', 'IFN-γ-producing', 'CD4(+)', and, 'CD8(+)', 'T', cells]), verbo([responding]), complemento([to, 'Listeria', monocytogenes, infection])]). relacion([sujeto(['These', findings, demonstrate, the, key, role, of, 'PRC2/Ezh2', in, differentiation, and, survival, of, peripheral, 'T', cells, and]), verbo([reveal]), complemento([potential, immunotherapeutic, targets])]). relacion([sujeto(['Six', '(', 60, '%', ')', of, 10, squamous, cell, carcinomas]), verbo([expressed]), complemento(['GATA-3', '(', mean, 'H-score', of, 102, ')'])]). relacion([sujeto(['Of', 22, urothelial, 'carcinomas,', 95, '%']), verbo([expressed]), complemento(['GATA-3', '(', mean, 'H-score', of, 170, ')'])]). relacion([sujeto(['A', few, cholangiocarcinomas, '(', 3, '%', ')', ',', pancreatic, adenocarcinomas, '(', 10, '%', ')', ',', and, gastric, carcinomas, '(', 2, '%', ')', weakly]), verbo([expressed]), complemento(['GATA-3', '(', mean, 'H-score', &, 'lt;50)'])]). relacion([sujeto(['Significant', reactivity, in, gynecologic, squamous, cell, carcinomas]), verbo([suggests]), complemento([that, 'GATA-3', alone, cannot, reliably, distinguish, these, tumors, from, urothelial, carcinoma])]). relacion([sujeto(['GATA3']), verbo([nuclear]), complemento([expression, was, evaluated, using, standard, immunohistochemistry])]). relacion([sujeto(['Our', study, is, the, first, to]), verbo([reveal]), complemento(['GATA3', expression, in, the, small, subset, of, lung, small, cell, carcinoma, that, should, be, taken, into, consideration, in, assigning, site, of, origin, in, advanced, small, cell, carcinoma, cases])]). relacion([sujeto(['Our', novel]), verbo([finding]), complemento([of, 'GATA3', positivity, in, 'one-third', of, bladder, small, cell, carcinoma, is, of, potential, value, in, differentiating, small, cell, carcinomas, of, prostate, origin, from, those, of, bladder, origin])]). relacion([sujeto(['Group', 2, innate, lymphoid, cells, '(', 'ILC2s)', were, shown, to, be]), verbo([involved]), complemento([in, the, initiation, and, coordination, of, 'Th2-type', immune, responses, in, allergic, disease, animal, models])]). relacion([sujeto(['Messenger', 'RNA', expression, levels, of, 'IL-5', and, 'IL-13', were]), verbo([increased]), complemento([in, 'CRSwNP', compared, with, 'controls,', while, mRNA, levels, of, 'IL-25', and, 'GATA3', were, significantly, reduced])]). relacion([sujeto(['Our', results, characterize, the, complex, interactions, between, 'ILC2s', and, other, 'Th2', response, elements, in, the, context, of, 'CRS', and]), verbo([suggest]), complemento([that, 'ILC2', enrichment, occurs, in, 'CRSwNP', and, in, allergic, 'CRS', patients])]). relacion([sujeto(['Nephrogenic', adenoma, '(', 'NA)', is, a, benign, lesion, of, the, urinary, tract]), verbo([associated]), complemento([with, injury, to, the, urothelium])]). relacion([sujeto(['Although', the, staining, characteristics, of, the, individual, components, of, the, 'PIN-4', cocktail]), verbo([have]), complemento([been, reported, for, 'NA,', no, study, has, described, the, expression, patterns, for, 'NA', when, the, stains, are, applied, as, a, cocktail])]). relacion([sujeto(['GATA-3', is, an, emerging, marker, of, urothelial, 'carcinoma;', 'however,', the, 'GATA-3', staining, characteristics, of, 'NA']), verbo([have]), complemento([yet, to, be, described])]). relacion([sujeto(['A', key, to, the, genesis, of, this, tumor, is, the, mutational]), verbo([loss]), complemento([of, the, 'BAF47', gene, as, well, as, the, widespread, epigenetic, suppression, of, other, key, anticancer, genes])]). relacion([sujeto(['Moreover,', 'BRM', can, be]), verbo([induced]), complemento([by, 'BAF47', 're-expression', and, by, 'Flavopiridol'])]). relacion([sujeto(['Similar', to, lung, cancer, cell, 'lines,', we]), verbo([found]), complemento([that, 'HDAC3,', 'HDAC9,', 'MEF2D', and, 'GATA3', controlled, 'BRM', silencing, and, that, 'HDAC9', was, overexpressed, in, 'Rhabdoid', cancer, cell, lines])]). relacion([sujeto(['In', primary, 'BRM-deficient', 'Rhabdoid', 'tumors,', 'HDAC9', was, also]), verbo([found]), complemento([to, be, highly, overexpressed])]). relacion([sujeto(['To', determine, how, these, polymorphisms, were, tied, to, 'BRM', 'silencing,', we, conducted, 'ChIP', assays, and]), verbo([found]), complemento([that, both, 'HDAC9', and, 'MEF2D', bound, to, the, 'BRM', promoter, at, or, near, these, polymorphic, sites])]). relacion([sujeto(['Using', 'BRM', promoter, swap, 'experiments,', we, indirectly, showed, that, both, 'HDAC9', and, 'MEF2D']), verbo([bound]), complemento([to, these, polymorphic, sites])]). relacion([sujeto(['Together,', these, data, show, that, the, mechanism, of, 'BRM', silencing, contributes, to, the, pathogenesis, of, 'Rhabdoid', tumors, and, appears, to, be]), verbo([conserved]), complemento([among, tumor, types])]). relacion([sujeto(['Although', plasma, levels, of, 'IL-27', are, shown, to, be]), verbo([associated]), complemento([with, 'cITP,', its, association, with, 'T', cell, subsets, has, not, been, studied])]). relacion([sujeto(['The', 'up-regulation', of, 'IL-27', might]), verbo([cause]), complemento(['Th1', differentiation, and, might, be, involved, in, the, pathophysiology, of, cITP])]). relacion([sujeto(['Its', gene, expression, is, limited, at, the, very, surface, of, the, stratum, granulosum, '(', 'SG),', whereas, expression, of, kallikreins, '(', 'KLKs)', encoding, proteases, is, usually]), verbo([found]), complemento([throughout, the, stratum, spinosum, and, 'SG'])]). relacion([sujeto(['Luciferase', assay]), verbo([targeting]), complemento([the, 'SPINK5', promoters, '(', nucleotide, -, 676, /, -, 532, and, -, 318, /, -, 146, from, the, major, transcription, start, 'site)', showed, high, intensity, in, 'NHEK', human, keratinocyte])]). relacion([sujeto(['Differentiation']), verbo([induced]), complemento([by, high, 'Ca(2+)', medium, failed, to, alter, their, luciferase, activities])]). relacion([sujeto(['Transfection', of, 'GATA3']), verbo([expressing]), complemento([vector, significantly, but, slightly, increased, them, and, that, of, vector, expressing, its, dominant, negative, form, decreased])]). relacion([sujeto(['Vestigial-like', 1, '(', 'VGLL1)', is, a, poorly, characterized, gene, encoding, a, transcriptional, 'co-activator', structurally, homologous, to, 'TAZ', and, 'YAP', that]), verbo([modulates]), complemento([the, 'Hippo', pathway, in, 'Drosophila'])]). relacion([sujeto(['Of', 28, miRNAs, differentially]), verbo([expressed]), complemento([in, estrogen, receptor, '(', 'ER)-positive', and, 'ER-negative', grade, 3, breast, 'carcinomas,', 'miR-934', was, most, strongly, upregulated, in, 'ER-negative', 'carcinomas,', and, its, expression, was, correlated, with, that, of, 'VGLL1'])]). relacion([sujeto(['Nuclear', 'VGLL1', expression, was, observed, in, 13, '%', of, sporadic, breast, 'carcinomas,', and, while, 'VGLL1', was, only, occasionally]), verbo([found]), complemento([in, luminal, 'A', '(', 0.7, '%', ')', and, 'B', '(', 5.6, '%', ')', 'carcinomas,', it, was, often, expressed, in, 'HER2-positive', '(', 17, '%', ')', ',', 'triple-negative', '(', 'TN)', breast, carcinomas, '(', &, 'gt;40%)', and, 'BRCA1-associated', 'TN', carcinomas, '(', &, 'gt;50%)'])]). relacion([sujeto(['Moreover,', 'VGLL1', expression, was]), verbo([associated]), complemento([with, reduced, overall, survival])]). relacion([sujeto(['In', 'conclusion,', 'VGLL1', and, 'miR-934', are, mainly]), verbo([expressed]), complemento([in, sporadic, and, 'BRCA1-associated', 'TN', 'basal-like', breast, 'carcinomas,', and, their, coordinated, 'expression,', at, least, partially, mediated, by, the, direct, modulation, of, 'ESR1,', might, be, involved, in, the, maintenance, of, a, luminal, progenitor, phenotype])]). relacion([sujeto(['Type', 1, myeloid, dendritic, cells, '(', 'mDCs)', contribute, to, inception, of, allergic, asthma, '(', 'AA)', and, are]), verbo([regulated]), complemento([by, 'epithelial-derived', cytokines])]). relacion([sujeto(['When', compared, to, mDCs, from, 'controls,', both, 'TSLP-', and, 'Der', 'p-pulsed', blood, mDCs, from, 'AA', patients]), verbo([induced]), complemento([increased, polarization, of, 'CD4+', 'T', cells, into, 'Th2', cells, '(', 'IL-5,', 'IL-13,', and, 'GATA3+),', while, only, 'TSLP-mDCs', promoted, 'Th9', cells, '(', 'IL-9', and, 'PU'])]). relacion([sujeto(['In', 'addition,', 'OX40L', was]), verbo([induced]), complemento([upon, 'TSLP', stimulation, and, was, required, for, the, induction, of, 'Th2,', but, not, 'Th9,', cells])]). relacion([sujeto(['These', data, further, highlight, the, 'TSLP', pathway, as, a, relevant]), verbo([target]), complemento([in, human, asthma])]). relacion([sujeto(['We']), verbo([find]), complemento([that, gene, expression, patterns, within, early, neoplasias, are, distinct, from, both, normal, and, breast, cancer, patterns, and, identify, a, pattern, of, 'pro-oncogenic', 'changes,', including, elevated, transcription, of, 'ERBB2,', 'FOXA1,', and, 'GATA3', at, this, early, stage])]). relacion([sujeto(['This', is, an, uncommon, variant, of, bladder, 'cancer,']), verbo([recognized]), complemento([by, the, current, 'WHO', classification, of, urologic, tumors])]). relacion([sujeto(['Most', neoplastic, cells, had, nuclei, of, low, to, intermediate]), verbo([nuclear]), complemento([grade, with, occasional, nuclear, 'enlargement,', most, frequently, seen, in, deep, areas, of, tumor])]). relacion([sujeto(['The', nested, component]), verbo([expressed]), complemento([cytokeratins, 7, ',', 20, ',', 'CAM5'])]). relacion([sujeto(['In', 'summary,', nested, variant, of, urothelial, bladder, carcinoma, is, typically]), verbo([associated]), complemento([with, advanced, stage])]). relacion([sujeto(['Whether', 'nuclear-WASp']), verbo([requires]), complemento([the, integration, of, its, 'actin-related', protein, '(', 'ARP)2/3-dependent', cytoplasmic, function, to, reprogram, gene, 'transcription,', 'however,', remains, unresolved])]). relacion([sujeto(['Using', the, model, of, human, 'TH', cell, 'differentiation,', we]), verbo([find]), complemento([that, 'WASp', has, a, functional, nuclear, localizing, and, nuclear, exit, 'sequences,', and, 'accordingly,', its, effects, on, transcription, are, controlled, mainly, at, the, level, of, its, nuclear, entry, and, exit, via, the, nuclear, pore])]). relacion([sujeto(['In', 'contrast,']), verbo([nuclear]), complemento([presence, of, 'WASp', in, 'TH2-skewed', cells, is, 'small,', and, its, loss, does, not, impair, transcriptional, reprogramming, of, 'GATA3', and, 'IL4', promoters])]). relacion([sujeto(['It', is, an, autosomal, dominant, condition]), verbo([caused]), complemento([by, mutations, in, the, 'GATA3', 'gene,', located, at, 10, 'p15,', a, critical, region, in, the, development, of, the, embryonic, parathyroid, 'glands,', inner, 'ear,', and, kidneys])]). relacion([sujeto(['Upon', chromosomal, microarray]), verbo([he]), complemento([was, found, to, have, an, interstitial, deletion, at, 10, 'p,', which, produced, a, partial, deletion, in, the, 'GATA3', gene])]). relacion([sujeto(['Research', in, mouse, and, human, clearly, identified, subsets, of, 'T', helper, '(', 'Th)', cells, based, on]), verbo([nuclear]), complemento([expression, of, specific, lineage, transcription, factors])]). relacion([sujeto(['T-bet', and, 'GATA-3', are, the, transcription, factors, that]), verbo([regulate]), complemento([commitment, to, 'Th1', or, 'Th2', 'cells,', respectively])]). relacion([sujeto(['Importantly,', 'GATA-3', and, 'T-bet']), verbo([expressing]), complemento([cells, were, detectable, in, pigs, infected, with, pathogens, associated, with, 'Th2', and, 'Th1', immune, responses])]). relacion([sujeto(['Increased', frequencies, of, 'GATA-3', positive, 'CD4(+)', cells, are]), verbo([found]), complemento([in, vivo, in, pigs, experimentally, infected, with, the, nematode, 'Trichuris', 'suis,', whereas, porcine, reproductive, and, respiratory, syndrome, virus, '(', 'PRRSV)', infection, elicited, 'T-bet', positive, 'CD4(+)', 'T', cells])]). relacion([sujeto(['Analysing', the, immune, status, of, 'pre-weaning', piglets, with, intrauterine, growth, restriction, '(', 'IUGR)', we]), verbo([found]), complemento([an, increased, expression, of, 'Foxp3,', 'T-bet', and, 'GATA-3', in, 'CD4(+)', and, 'CD4(+)CD8(+)', 'double-positive', 'T', cells, in, systemic, and, intestinal, compartments, of, 'IUGR', piglets])]). relacion([sujeto(['Hence,', we, established, the, detection, of, porcine, 'Th1', and, 'Th2', cells, via, 'T-bet', and, 'GATA-3', and, show, that, the, porcine, lineage, transcription, factors, are, differentially]), verbo([regulated]), complemento([very, early, in, life, depending, on, the, developmental, status])]). relacion([sujeto(['Physical', 'stressors,', such, as, strenuous, 'exercise,', can]), verbo([have]), complemento([numerous, effects, on, the, human, body, including, the, immune, system])]). relacion([sujeto(['We']), verbo([found]), complemento([that, 'PBMC', express, a, characteristic, 'Th2-like', gene, profile, one, week, 'post-marathon', compared, to, 'pre-marathon'])]). relacion([sujeto(['These', findings]), verbo([suggest]), complemento([that, a, 'Th1/Th2', immune, imbalance, persisted, at, least, 1, week, after, completion, of, a, marathon, which, offers, a, mechanistic, rationale, for, the, increased, risk, of, upper, respiratory, tract, infections, often, reported, after, strenuous, exercise])]). relacion([sujeto(['Response', to, 'FAE', treatment, was]), verbo([associated]), complemento([with, a, '≥', 2, -, fold, change, '(', 'P', &, 'lt;', 0.05, ')', in, the, expression, of, 458, genes])]). relacion([sujeto(['Glutathione', and, 'Nrf2', pathway, molecules, were, specifically]), verbo([induced]), complemento([by, 'FAE', treatment, and, not, by, etanercept, 'treatment,', representing, an, 'FAE-specific', effect, in, psoriatic, skin])]). relacion([sujeto(['In', 'addition,', 'FAE', treatment, specifically]), verbo([induced]), complemento([the, transcription, factors, 'PTTG1,', 'NR3C1,', 'GATA3', and, 'NFκBIZ', in, responding, patients])]). relacion([sujeto(['FAE', treatment]), verbo([induces]), complemento([glutathione, and, 'Nrf2', pathway, genes, in, lesional, skin, of, patients, with, psoriasis])]). relacion([sujeto(['In', 'responders,', 'FAEs', specifically]), verbo([regulate]), complemento([the, transcription, factors, 'PTTG1,', 'NR3C1,', 'GATA3', and, 'NFκBIZ,', which, are, important, in, normal, cutaneous, 'development,', and, the, 'T-helper', '(', 'Th)2', and, 'Th17', 'pathways,', respectively])]). relacion([sujeto(['As', a, global, approach, to]), verbo([gain]), complemento([insights, into, the, potential, regulatory, role, of, miRNA, in, mast, cell, differentiation, we, characterised, expression, in, 'BM', cultures, from, the, initiation, of, differentiation])]). relacion([sujeto(['In', cultures, enriched, in, differentiating, mast, cells, we, characterised, miRNA, expression, and, identified, miRNA]), verbo([targeting]), complemento([the, mRNA, of, putative, factors, involved, in, differentiation, pathways, and, cellular, identity])]). relacion([sujeto(['We', identified, 86, unique, miRNAs, with, expression, patterns, that, were, 'up-', or, 'down-']), verbo([regulated]), complemento([at, 5, -, fold, or, more, during, bone, marrow, derived, mast, cells, '(', 'BMMC)', development])]). relacion([sujeto(['By', employing, 'TargetScan', and, 'MeSH', 'databases,', we, identified, 524, transcripts]), verbo([involved]), complemento([in, 30, canonical, pathways, as, potentially, regulated, by, these, specific, 86, miRNAs])]). relacion([sujeto(['Furthermore,', by, applying, miRanda, and, 'IPA', 'analyses,', we, predict, that, 7, specific, miRNAs, of, this, group, are, directly]), verbo([associated]), complemento([with, the, expression, of, 'c-Kit', and, 'FcεRIα', and, 'likewise,', that, 18, miRNAs, promote, expression, of, 'Mitf,', 'GATA1', and, 'c/EBPα', three, core, transcription, factors, that, direct, mast, cell, differentiation])]). relacion([sujeto(['Furthermore,', we]), verbo([have]), complemento([identified, 11, miRNAs, that, may, regulate, the, expression, of, 'STATs-3,', -, 5, 'a/b,', 'GATA2', and, 'GATA3', during, 'differentiation,', along, with, 13, miRNAs, that, target, transcripts, encoding, 'Ndst2,', mMCP4, and, mMCP6, and, thus, may, regulate, biosynthesis, of, mast, cell, secretory, mediators])]). relacion([sujeto(['This', investigation, characterises, changes, in, miRNA, expression, in, whole, 'BM', cultures, during, the, differentiation, of, mast, cells, and, predicts, functional, links, between, miRNAs, and, their]), verbo([target]), complemento([mRNAs, for, the, regulation, of, development])]). relacion([sujeto(['This', information]), verbo([provides]), complemento([an, important, resource, for, further, investigations, of, the, contributions, of, miRNAs, to, mast, cell, differentiation, and, function])]). relacion([sujeto(['Poly(ADP-ribose)', 'polymerase-1', '(', 'PARP-1)', synthesizes, and, transfers, 'ADP', ribose, polymers, to]), verbo([target]), complemento(['proteins,', and, regulates, 'DNA', repair, and, genomic, integrity, maintenance])]). relacion([sujeto(['PARP-1', also, plays, a, crucial, role, in, the, progression, of, the, inflammatory, 'response,', and, its, inhibition]), verbo([confers]), complemento([protection, in, several, models, of, inflammatory, disorders])]). relacion([sujeto(['We', investigated, the, possible, 'anti-arthritic', effects, of, the, 'PARP-1', inhibitor, 5, -, aminoisoquinolinone, '(', 5, -, 'AIQ)', in, a, mouse, model, of, adjuvant]), verbo([induced]), complemento([arthritis, '(', 'AIA)'])]). relacion([sujeto(['In', this, 'study,', we, examined, the, effects, of, 5, -, 'AIQ', on, the, key, mediators, of, arthritic, 'inflammation,', 'namely,', edema, and, arthritic, 'score,', 'T', cell, 'subsets,', regulatory, 'T', '(', 'Treg)', 'cells,', 'IL-17A,', 'GITR']), verbo([expressing]), complemento(['cells,', 'NF-kB', 'p65,', 'IkB-α', and, pro, and, 'anti-inflammatory', mediators, mRNA, expression, levels])]). relacion([sujeto(['PARP-1', inhibition, 5, -, 'AIQ', treatment, significantly, attenuated, the, severity, of, 'AIA,', reduced, the, arthritis, 'scores,', a, substantial, reduction, in, the, levels, of, 'T', cell, 'subsets,', 'IL-17A,', 'NF-kB', 'p65,', 'GITR']), verbo([expressing]), complemento(['cells,', and, as, well, as, the, 'pro-inflammatory', mediators])]). relacion([sujeto(['Our', results]), verbo([suggest]), complemento([that, treatment, with, 5, -, 'AIQ', attenuated, 'AIA', in, mice, might, offer, a, promising, 'alternative/adjunct', treatment, for, 'RA'])]). relacion([sujeto(['Carbon', monoxide, '(', 'CO)', is, endogenously, produced, by, haeme, 'oxygenase-1', and]), verbo([has]), complemento([profound, effects, on, intracellular, signalling, 'processes,', generating, 'anti-inflammatory,', antiproliferative, and, antiapoptotic, effects])]). relacion([sujeto(['A', 'boron-containing', compound, 'CORM-A1', is, capable, of]), verbo([releasing]), complemento(['CO', in, such, a, way, to, mimic, physiological, functions, of, haeme, 'oxygenase-1'])]). relacion([sujeto(['Furthermore,', 'CORM-A1', efficiently, reduced, the, percentage, of, 'CD4(+)', 'IFN-γ(+)', and, 'CD4(+)', 'IL-17(+)', 'cells,', whereas, 'CD4(+)', 'IL-4(+)', cell, population]), verbo([increased]), complemento([after, treatment])]). relacion([sujeto(['In', 'conclusion,', our, findings, indicate, that, 'CO']), verbo([has]), complemento(['anti-inflammatory', role, through, the, regulation, of, balance, between, 'pro-inflammatory', 'Th1/Th17', and, 'anti-inflammatory', 'Th2', cells])]). relacion([sujeto(['Here,', we]), verbo([have]), complemento([analyzed, the, activity, of, 'NKL', homeobox, gene, 'MSX1', using, pediatric, 'T-ALL', in, silico, 'data,', detecting, overexpression, in, 11, '%', of, patients])]). relacion([sujeto(['Comparative', expression, profiling, indicated, inhibition, of, the, bone, morphogenetic, protein, '(', 'BMP)', signaling, 'pathway,', which, was, shown, to]), verbo([inhibit]), complemento(['MSX1', transcription])]). relacion([sujeto(['In', the, 'LOUCY', cell, line, we, identified, conspicuous, expression, of, 'CHRDL1', encoding, a, 'BMP', inhibitor, which]), verbo([mediated]), complemento([activation, of, 'MSX1'])]). relacion([sujeto(['Furthermore,', knockdown, and, overexpression, studies, of, hematopoietic, transcription, factors, demonstrated, that, 'GATA2', and, 'FOXC1']), verbo([mediate]), complemento([activation, and, 'GATA3,', 'LEF1,', 'TAL1', and, 'TOX', repression, of, 'MSX1', transcription])]). relacion([sujeto(['Collectively,', our, findings]), verbo([suggest]), complemento([that, 'MSX1', is, physiologically, restricted, to, lymphoid, progenitors])]). relacion([sujeto(['The', identification, of, deregulated, 'BMP', signaling, may]), verbo([provide]), complemento([novel, therapeutic, options, for, the, treatment, of, 'T-ALL'])]). relacion([sujeto(['Estrogen']), verbo([has]), complemento([potent, immunomodulatory, effects, on, proinflammatory, 'responses,', which, can, be, mediated, by, serine, proteases])]). relacion([sujeto(['We', now, demonstrate, that, estrogen]), verbo([increased]), complemento([the, extracellular, expression, and, 'IL-12-induced', activity, of, a, critical, member, of, serine, protease, family, 'Granzyme', 'A,', which, has, been, shown, to, possess, a, novel, inflammatory, persona])]). relacion([sujeto(['The', inhibition, of, serine, protease, activity, with, inhibitor, 4, -, '(', 2, -, 'aminoethyl)', benzenesulfonyl, fluoride, hydrochloride, significantly, diminished]), verbo([enhanced]), complemento([production, of, proinflammatory, 'interferon-γ,', 'IL-1β,', 'IL-1α,', and, 'Granzyme', 'A', activity, even, in, the, presence, of, a, 'Th1-inducing', 'cytokine,', 'IL-12', from, splenocytes, from, in, vivo, 'estrogen-treated', mice])]). relacion([sujeto(['Inhibition', of, serine, protease, activity, selectively]), verbo([promoted]), complemento([secretion, of, 'Th2-specific', 'IL-4,', nuclear, phosphorylated, 'STAT6A,', signal, transducer, and, activator, of, transcription, '(', 'STAT)6A', 'translocation,', and, 'STAT6A', 'DNA', binding, in, 'IL-12-stimulated', splenocytes, from, 'estrogen-treated', mice])]). relacion([sujeto(['Although', serine, protease, inactivation]), verbo([enhanced]), complemento([the, expression, of, 'Th2-polarizing', 'factors,', it, did, not, reverse, 'estrogen-modulated', decrease, of, phosphorylated, 'STAT5,', a, key, factor, in, 'Th2', development])]). relacion([sujeto(['Collectively,', data]), verbo([suggest]), complemento([that, serine, protease, inactivity, augments, the, skew, toward, a, 'Th2-like', profile, while, 'down-regulating', 'IL-12-induced', proinflammatory, 'Th1', biomolecules, upon, in, vivo, estrogen, 'exposure,', which, implies, serine, proteases, as, potential, regulators, of, inflammation])]). relacion([sujeto(['Thus,', these, studies, may]), verbo([provide]), complemento([a, potential, mechanism, underlying, the, immunomodulatory, effect, of, estrogen, and, insight, into, new, therapeutic, strategies, for, proinflammatory, and, 'female-predominant', autoimmune, diseases])]). relacion([sujeto(['It', is]), verbo([expressed]), complemento([preferentially, in, the, 'T', lineage, among, hematopoietic, cells, and, is, induced, by, 'MHC-mediated', positive, selection])]). relacion([sujeto(['Here', we, showed, 'Itm2a', to, be, a]), verbo([target]), complemento([gene, of, 'GATA-3,', a, 'T', 'cell-specific', transcription, factor])]). relacion([sujeto(['We', further, demonstrated, that, 'Itm2b', but, not, 'Itm2c', was, also]), verbo([expressed]), complemento([in, 'T', 'cells,', and, was, induced, upon, 'activation,', albeit, following, a, kinetic, different, from, that, of, 'Itm2a'])]). relacion([sujeto(['GATA3', is]), verbo([expressed]), complemento([in, most, cases, of, sarcomatoid, urothelial, carcinoma])]). relacion([sujeto(['Kruppel-like', factor, '(', 'KLF)', 13, is, a, transcription, factor, that, positively]), verbo([regulates]), complemento([expression, of, the, chemokine, 'RANTES', 3, -, 5, d, after, activation, of, 'T', cells])]). relacion([sujeto(['Gene', expression, analysis, in]), verbo([activated]), complemento(['T', cells, from, 'Klf13(-/-)', mice, showed, that, 'IL-4,', along, with, other, 'Th2', cytokine, 'genes,', was, downregulated, when, compared, with, cells, from, 'wild-type', mice])]). relacion([sujeto(['The']), verbo([decreased]), complemento([levels, of, 'IL-4', were, not, associated, with, changes, in, expression, of, the, 'Th2-inducing', transcription, factors, 'GATA3', or, 'c-Maf'])]). relacion([sujeto(['Additional', analysis, revealed, that, 'KLF13', directly]), verbo([binds]), complemento([to, 'IL-4', promoter, regions, and, synergizes, with, 'c-Maf', to, positively, regulate, 'IL-4', expression])]). relacion([sujeto(['These', results, indicate, that, 'KLF13', is, a, positive, regulator, for, differentiation, of, 'Th2', 'cells,', as, part, of, the, transcriptional, machinery, that]), verbo([regulates]), complemento(['IL-4', production, in, 'Th2', cells])]). relacion([sujeto(['Proper', development, of, 'T', cells, depends, on, 'lineage-specific', regulators, controlled, transcriptionally, and, posttranslationally, to]), verbo([ensure]), complemento([precise, levels, at, appropriate, times])]). relacion([sujeto(['Similar', perturbations, during, development, of, 'CD8-positive', cells, were]), verbo([reported]), complemento([with, transgenic, 'mice,', which, enforced, 'GATA3', '(', 'T-cell', differentiation, 'regulator)', expression, throughout, 'T-cell', development])]). relacion([sujeto(['Using', overexpressed, proteins, in, cultured, 'cells,', we, demonstrated, that, 'Fbw7']), verbo([bound]), complemento(['to,', 'ubiquitylated,', and, destabilized, 'GATA3'])]). relacion([sujeto(['Two', 'Cdc4', phosphodegron, '(', 'CPD)', candidate, 'sequences,', consensus, 'Fbw7', recognition, 'domains,', were, identified, in, 'GATA3,', and, phosphorylation, of, 'Thr-156', in, 'CPD', was]), verbo([required]), complemento([for, 'Fbw7-mediated', ubiquitylation, and, degradation])]). relacion([sujeto(['These', observations]), verbo([suggest]), complemento([that, 'Fbw7-mediated', 'GATA3', regulation, with, 'CDK2-mediated', phosphorylation, of, 'CPD', contributes, to, the, precise, differentiation, of, 'T-cell', lineages])]). relacion([sujeto(['CD70-expressing', 'CD4', 'T', cells, are, enriched, in, 'RA', and]), verbo([promote]), complemento([autoimmunity, via, 'co-stimulatory', 'CD70-CD27', interaction])]). relacion([sujeto(['CD4', 'T', cells, of, healthy, controls, rarely]), verbo([expressed]), complemento(['CD70', as, compared, with, 'CD4', 'T', cells, of, 'RA', patients, '[', mean, 0.9, '%', '(', s])]). relacion([sujeto(['CD70(+)', 'CD4', 'T', cells, preferentially]), verbo([expressed]), complemento([transcription, factor, 'RORγt'])]). relacion([sujeto(['Of', the, 'triple-negative', breast, 'carcinomas,', 100, '%']), verbo([expressed]), complemento([claudin, 4, ;, 5, '%', ',', keratin, 5, /, 6, ;, 30, '%', ',', 'GATA3;', 18, '%', ',', 'mammaglobin;', 15, '%', ',', 'GCDFP-15;', 56, '%', ',', 'mesothelin;', 38, '%', ',', 'calretinin;', 18, '%', ',', 'thrombomodulin;', 5, '%', ',', 'WT1;', and, 3, '%', ',', podoplanin])]). relacion([sujeto(['Among', the, estrogen, 'receptor-positive', breast, 'carcinomas,', 100, '%', were, claudin, 4, and, 'GATA3', 'positive;', 70, '%']), verbo([expressed]), complemento(['GCDFP-15;', 63, '%', ',', 'mammaglobin;', 13, '%', ',', 'calretinin;', 13, '%', ',', 'thrombomodulin;', 8, '%', ',', 'WT1;', 5, '%', ',', keratin, 5, /, 6, ;, 3, '%', ',', 'mesothelin;', and, 0, '%', ',', podoplanin])]). relacion([sujeto(['CD4(+)', 'Th2', development, is]), verbo([regulated]), complemento([by, the, zinc, finger, transcription, factor, 'GATA3'])]). relacion([sujeto(['Once']), verbo([induced]), complemento([by, acute, priming, 'signals,', such, as, 'IL-4,', 'GATA3', poises, the, 'Th2', cytokine, locus, for, rapid, activation, and, establishes, a, 'positive-feedback', loop, that, maintains, elevated, 'GATA3', expression])]). relacion([sujeto(['Type', 'I', 'IFN', '(', 'IFN-α/β)']), verbo([inhibits]), complemento(['Th2', cells, by, blocking, the, expression, of, 'GATA3', during, 'Th2', development, and, in, fully, committed, 'Th2', cells])]). relacion([sujeto(['IFN-α/β']), verbo([suppressed]), complemento([expression, of, 'GATA3', mRNA, that, was, transcribed, from, an, alternative, distal, upstream, exon, '(', 1, 'A)'])]). relacion([sujeto(['This', suppression, was, not]), verbo([mediated]), complemento([through, 'DNA', 'methylation,', but, rather, by, histone, modifications, localized, to, a, conserved, noncoding, sequence, '(', 'CNS-1)', upstream, of, exon, 1, 'A'])]). relacion([sujeto(['IFN-α/β', treatment]), verbo([led]), complemento([to, a, closed, conformation, of, 'CNS-1,', as, assessed, by, 'DNase', 'I', 'hypersensitivity,', along, with, enhanced, accumulation, of, 'H3K27me3', mark, at, this, 'CNS', 'region,', which, correlated, with, increased, density, of, total, nucleosomes, at, this, putative, enhancer])]). relacion([sujeto(['Consequently,', accessibility, of, 'CNS-1', to, 'GATA3', 'DNA']), verbo([binding]), complemento([activity, was, reduced, in, response, to, 'IFN-α/β', 'signaling,', even, in, the, presence, of, 'IL-4'])]). relacion([sujeto(['Thus,', 'IFN-α/β', disrupts, the, 'GATA3-autoactivation', loop, and]), verbo([promotes]), complemento([epigenetic, silencing, of, a, 'Th2-specific', regulatory, region, within, the, 'GATA3', gene])]). relacion([sujeto(['The', most, common, gene, alterations, '(', in, order, of]), verbo([decreasing]), complemento(['frequency)', 'included:', 'TP53,', 'PIK3CA,', 'CCND1,', 'MYC,', 'HER2', '(', 'ERBB2),', 'MCL1,', 'PTEN,', 'FGFR1,', 'GATA3,', 'NF1,', 'PIK3R1,', 'BRCA2,', 'EGFR,', 'IRS2,', 'CDH1,', 'CDKN2A,', 'FGF19,', 'FGF3', and, 'FGF4'])]). relacion([sujeto(['Many', of, these, aberrations, represent, druggable, 'targets,', either, through, direct, pathway, inhibition, or, through, an]), verbo([associated]), complemento([pathway, '(', via, '\'', 'crosstalk\')'])]). relacion([sujeto(['The', '\'', molecular, 'individuality\'', of, these, tumors]), verbo([suggests]), complemento([that, a, customized, 'strategy,', using, an, &, 'quot;N-of-One"', model, of, precision, 'medicine,', may, represent, an, optimal, approach, for, the, treatment, of, patients, with, advanced, tumors])]). relacion([sujeto(['Growth', factor, receptor]), verbo([bound]), complemento([protein, 2, -, associated, binder, '(', 'Gab)', 2, ',', a, scaffolding, adaptor, 'protein,', negatively, regulates, signaling, pathways, critical, for, 'T', 'cell-mediated', immunity])]). relacion([sujeto([mRNA, levels, of, 'Gab2', and, its, correlated, family, 'member,', 'Gab1,', were, markedly]), verbo([decreased]), complemento([in, untreated, patients, with, pulmonary, 'TB', compared, with, healthy, control, subjects])]). relacion([sujeto(['Importantly,', this]), verbo([decreased]), complemento(['Gab2', expression, to, normal, levels, after, bacterial, load, in, the, 'patient\'s', sputum, became, undetectable, under, the, standard, 'anti-TB', 'treatment,', which, negatively, correlated, with, the, level, of, 'M'])]). relacion([sujeto([tuberculosis, infection, mouse, 'model,', infected, 'Gab2-deficient', mice, exhibited]), verbo([decreased]), complemento([bacterial, load, and, milder, lung, pathological, damage, compared, with, infected, 'wild-type', 'mice,', accompanied, by, decreased, production, of, 'IL-2,', 'IL-6,', and, 'granulocyte/macrophage', 'colony-stimulating', factor, proinflammatory, 'cytokines,', and, an, increased, 'T-cell-specific', 'T-box', transcription, 'factor/GATA', binding, protein, 3, expression, ratio])]). relacion([sujeto([tuberculosis, 'infection,']), verbo([revealed]), complemento([a, potential, negative, regulatory, role, for, 'Gab2', in, immunity, to, 'TB'])]). relacion([sujeto(['Recent', studies]), verbo([have]), complemento([demonstrated, that, extracellular, adenosine, 5, '\'', -, 'triphosphate (eATP)', is, involved, in, allergic, airway, inflammation, by, activating, purinergic, receptors])]). relacion([sujeto(['Furthermore,', apyrase, also, markedly, reduced, the, expression, of, 'GATA']), verbo([binding]), complemento(['protein 3', '(', 'GATA3)', and, decreased, the, chemotactic, migration, of, 'DCs', towards, 'ATP'])]). relacion([sujeto(['Our', data, demonstrate, that, a, reduction, in, 'CD39', expression, may, be]), verbo([associated]), complemento([with, the, development, of, allergic, airway, inflammation, and, that, apyrase, alleviates, airway, inflammation, by, decreasing, the, chemotactic, migration, of, 'DCs', towards, eATP])]). relacion([sujeto(['Therefore,']), verbo([targeting]), complemento([at, eATP, or, ectonucleotidases, may, provide, a, novel, therapeutic, approach, for, allergic, asthma])]). relacion([sujeto(['The', mechanistic]), verbo([target]), complemento([of, rapamycin, '(', 'mTOR)', signaling, integrates, diverse, environmental, 'cues,', including, growth, 'factors,', nutrients, and, immunological, signals])]). relacion([sujeto(['Activation', of, mTOR, signaling]), verbo([stimulates]), complemento([protein, synthesis, and, anabolic, metabolism, and, coordinates, cell, 'growth,', proliferation, and, fate, decisions])]). relacion([sujeto(['In', recent, 'years,', mTOR, signaling]), verbo([has]), complemento([been, linked, to, the, entire, spectrum, of, 'T', cell, 'biology,', ranging, from, 'T', cell, development, and, activation, to, lineage, specification, and, memory, formation])]). relacion([sujeto(['Mechanistically,', mTOR, activation, profoundly, affects, the, expression, and, activity, of, many, immunologically, relevant, transcription, factors, to, propagate, immune, signaling, and]), verbo([mediate]), complemento([effector, functions])]). relacion([sujeto(['This', review, discusses, how, mTOR, 'signaling,', through, impinging, upon, transcriptional, 'factors,']), verbo([regulates]), complemento(['T', cell, 'development,', 'activation,', and, effector, and, memory, differentiation])]). relacion([sujeto(['The', 'JmjC', 'domain-containing', 'H3K4', histone, demethylase, jumonji, 'AT-rich', interactive, domain, 1, 'B', '(', 'JARID1B)', '(', also, known, as, 'KDM5B', and, 'PLU1)', is, overexpressed, in, breast, cancer, and, is, a, potential]), verbo([target]), complemento([for, breast, cancer, treatment])]). relacion([sujeto(['Unlike', previously]), verbo([reported]), complemento(['Jarid1b(-/-)', 'strains,', the, majority, of, these, 'Jarid1b(-/-)', mice, were, viable, beyond, embryonic, and, neonatal, stages])]). relacion([sujeto(['This', allowed, us, to, further, examine, phenotypes]), verbo([associated]), complemento([with, the, loss, of, 'JARID1B', in, pubertal, development, and, pregnancy])]). relacion([sujeto(['These', 'Jarid1b(-/-)', mice, exhibited]), verbo([decreased]), complemento([body, 'weight,', premature, 'mortality,', decreased, female, 'fertility,', and, delayed, mammary, gland, development])]). relacion([sujeto(['Related', to, these, 'phenotypes,', 'JARID1B']), verbo([loss]), complemento([decreased, serum, estrogen, level, and, reduced, mammary, epithelial, cell, proliferation, in, early, puberty])]). relacion([sujeto(['In', mammary, epithelial, 'cells,', 'JARID1B']), verbo([loss]), complemento([diminished, the, expression, of, key, regulators, for, mammary, morphogenesis, and, luminal, lineage, 'specification,', including, 'FOXA1', and, estrogen, receptor, α])]). relacion([sujeto(['Mechanistically,', 'JARID1B', was]), verbo([required]), complemento([for, 'GATA3', recruitment, to, the, 'Foxa1', promoter, to, activate, 'Foxa1', expression])]). relacion([sujeto(['These', results, indicate, that, 'JARID1B', positively]), verbo([regulates]), complemento([mammary, ductal, development, through, both, extrinsic, and, 'cell-autonomous', mechanisms])]). relacion([sujeto(['Recently,', we]), verbo([have]), complemento([reported, that, 'lymphocyte-derived', endogenous, catecholamines, '(', 'CAs)', facilitate, a, shift, in, the, 'T', helper, '(', 'Th)1/Th2', balance, towards, 'Th2'])]). relacion([sujeto(['Lymphocytes', were, separated, from, the, mesenteric, lymph, nodes, of, 'mice,']), verbo([stimulated]), complemento([with, concanavalin, 'A', '(', 'Con', 'A)', and, treated, with, 'pargyline,', an, inhibitor, of, 'CA', degradation])]). relacion([sujeto(['These', results, imply, that, 'lymphocyte-derived', 'CAs']), verbo([promote]), complemento([polarization, of, differentiation, and, function, towards, 'Th2', cells, and, that, this, effect, is, mediated, by, 'α1-AR', and, 'β2-AR'])]). relacion([sujeto(['Th9', cells]), verbo([have]), complemento([been, reported, to, contribute, to, immune, 'responses;', 'however,', the, role, of, 'Th9', cells, in, 'Echinococcus', granulosus, infection, is, unknown])]). relacion([sujeto(['This', study, is, to, determine, whether, 'Th9', cells, and, 'IL-9', are]), verbo([involved]), complemento([in, human, 'Echinococcus', granulosus, infection])]). relacion([sujeto([1, ',', 'IL-9,', and, 'GATA-3', were, significantly]), verbo([increased]), complemento([in, patients, before, therapy, '(', 'CE', 'group),', as, revealed, by, 'qRT-PCR'])]). relacion([sujeto([1, and, 'GATA-3', mRNA, levels, were, significantly]), verbo([decreased]), complemento([in, patients, after, therapy, '(', 'PCE', 'group)', compared, with, 'CE', group])]). relacion([sujeto(['The', numbers, of, 'Th9', and, 'Th2', cells, and, levels, of, 'IL-9,', 'IL-4,', 'IL-10,', and, 'TGF-', β, were, also, significantly]), verbo([decreased]), complemento([in, 'PCE', group])]). relacion([sujeto(['In', 'conclusion,', the, ratios, of, 'Th9', cells, and, 'IL-9', levels, were, significantly]), verbo([decreased]), complemento([after, 'treatment,', suggesting, that, 'Th9/IL-9', may, be, involved, in, immune, response, induced, by, 'Echinococcus', granulosus, infection])]). relacion([sujeto(['Estrogen', receptor, alpha, '(', 'ERα)', expression, is, critical, for, breast, cancer, 'classification,', high, 'ERα', expression, being]), verbo([associated]), complemento([with, better, prognosis])]). relacion([sujeto(['ERα', levels, strongly, correlate, with, that, of, 'GATA']), verbo([binding]), complemento([protein, 3, '(', 'GATA3),', a, major, regulator, of, 'ERα', expression])]). relacion([sujeto(['Further,', mathematical, modeling]), verbo([reveals]), complemento([that, 'GATA3', positively, regulates, its, own, expression, and, that, 'ERα', autoregulation, is, most, likely, absent])]). relacion([sujeto(['Lastly,', we, show, that, the, two, 'cross-regulatory', connections, in, the, 'ERα-GATA3', negative, feedback, network]), verbo([decrease]), complemento([the, noise, in, 'ERα', or, 'GATA3', expression])]). relacion([sujeto(['This', may]), verbo([ensure]), complemento([robust, cell, fate, maintenance, in, the, face, of, intracellular, and, environmental, 'fluctuations,', contributing, to, tissue, homeostasis, in, normal, 'conditions,', but, also, to, the, maintenance, of, pathogenic, states, during, cancer, progression])]). relacion([sujeto(['In', this, 'study,', 'OVA-induced', asthma, mice, was, taken, as, the, 'model,', and, orally, administered, with, different, concentration, of, ethanol, extracts, of, crude, and, processed, 'Stemona', 'tuberosa,', in, order, to, determine, the, cytokine, level]), verbo([released]), complemento([from, 'Th1', and, 'Th2', in, splenocytes])]). relacion([sujeto(['According', to, the, 'results,', compared, with, the, crude, 'samples,', processed, samples, significantly]), verbo([increased]), complemento([the, levels, of, inflammatory, factor, 'INF-gamma', '(', 'P', &, 'lt;', 0.05, ')', and, decreased, 'IL-5', '(', 'P', &, 'lt;', 0.05, ')', in, splenocytes])]). relacion([sujeto(['According', to, the, 'RT-PCR', 'results,', the, administration, of, processed, samples, could]), verbo([increase]), complemento([the, ratio, of, 'T-bet/GATA-3', '(', 'P', &, 'lt;', 0.05, ')'])]). relacion([sujeto([tuberosa, could, treat, asthma, by]), verbo([regulating]), complemento(['Th1/Th2', 'ratio,', but, processed, samples, showed, more, notable, effect])]). relacion([sujeto([tuberosa, in, clinical, treatment, of, asthma, and, chronic, 'cough,', which, layed, a, foundation, for, further]), verbo([revealed]), complemento([the, processing, mechanism, of, 'S'])]). relacion([sujeto(['GATA3']), verbo([has]), complemento([conventionally, been, regarded, as, a, transcription, factor, that, drives, the, differentiation, of, 'T', helper, '(', 'Th)', 2, cells])]). relacion([sujeto(['GATA3']), verbo([regulates]), complemento(['T', cell, 'development,', 'proliferation,', and, maintenance])]). relacion([sujeto(['Furthermore,', recent, studies]), verbo([have]), complemento([demonstrated, important, roles, for, 'GATA3', in, innate, lymphoid, cells])]). relacion([sujeto(['Data', on, immunohistochemical, expression, of, novel, and, traditional, urothelial, markers, in, the, wide, range, of, urothelial, carcinoma, variants]), verbo([have]), complemento([so, far, been, very, limited])]). relacion([sujeto(['This', study]), verbo([provides]), complemento([comprehensive, data, for, novel, and, traditionally, used, markers, to, support, urothelial, lineage, in, urothelial, carcinoma, variants])]). relacion([sujeto(['In', this, 'study,', we, show, the, appearance, of, a, distinct, 'CD4(+)', 'T', cell, subset]), verbo([expressing]), complemento(['IL-4', at, an, early, stage, of, development, in, infant, adenoids, and, cord, blood, that, is, lost, during, aging])]). relacion([sujeto(['We', identified, by, flow, 'cytometric,', fluorescent, 'microscopic,', 'immunoblot,', and, mass, spectrometric, analysis, a, population, of, 'CD4(+)', 'T', cells, that]), verbo([expressed]), complemento([an, unglycosylated, isoform, of, 'IL-4'])]). relacion([sujeto(['This', 'T', cell, subpopulation, was]), verbo([found]), complemento([in, neonatal, but, not, in, adult, 'CD4(+)', 'T', cells])]). relacion([sujeto(['Furthermore,', we, show, that, the, mRNA, of, the, 'Th2', master, transcription, factor, 'GATA3', is, preferentially]), verbo([expressed]), complemento([in, neonatal, 'CD4(+)', 'T', cells])]). relacion([sujeto(['Notably,', the, secretion, of, 'IL-4']), verbo([requires]), complemento([a, so, far, unidentified, trigger, in, neonatal, 'T', cells])]). relacion([sujeto(['This', emphasizes, that, cytokine, expression, and, secretion, are, differentially]), verbo([regulated]), complemento([processes])]). relacion([sujeto(['Our', data, support, the, hypothesis, of, an, endogenously, poised, cytokine, profile, in, neonates, and]), verbo([suggest]), complemento([a, link, between, cytokine, production, and, the, developmental, stage, of, an, organism])]). relacion([sujeto(['The', determination, of, the, 'IL-4', 'isoform-expressing', cells, in, humans, might, allow, the, identification, of, 'Th2', precursor, 'cells,', which, could]), verbo([provide]), complemento([novel, intervention, strategies, directed, against, 'Th2-driven', immunopathologies, such, as, allergies])]). relacion([sujeto(['Innate', lymphoid, cells, '(', 'ILCs)', are, lymphoid, cells, that, do, not]), verbo([express]), complemento([rearranged, receptors, and, have, important, effector, and, regulatory, functions, in, innate, immunity, and, tissue, remodeling])]). relacion([sujeto(['Group', 1, 'ILCs', '(', 'ILC1s)', produce, interferon, γ, and, depend, on, 'Tbet,', group, 2, 'ILCs', '(', 'ILC2s)', produce, type, 2, cytokines, like, 'interleukin-5', '(', 'IL-5)', and, 'IL-13', and]), verbo([require]), complemento(['GATA3,', and, group, 3, 'ILCs', '(', 'ILC3s)', include, lymphoid, tissue, inducer, 'cells,', produce, 'IL-17', 'and/or', 'IL-22,', and, are, dependent, on, 'RORγt'])]). relacion([sujeto(['In', this, 'review,', we]), verbo([provide]), complemento([an, overview, of, the, characteristics, of, 'ILCs', in, the, context, of, health, and, disease])]). relacion([sujeto(['In', this, 'study,', we]), verbo([induced]), complemento(['DSS', colitis, in, 'Th1', dominant, '(', 'T-bet', transgenic, '(', 'Tg))', 'mice,', 'Th2', dominant, '(', 'GATA-3', 'Tg)', 'mice,', and, 'Th17', dominant, '(', 'RORγt', 'Tg)', mice, to, elucidate, the, roles, of, 'T', helper, cell, in, 'DSS', colitis])]). relacion([sujeto(['GATA-3', 'Tg', mice, showed, a, significant]), verbo([decreased]), complemento([in, weight, from, day, 1, to, day, 7, ',', and, an, increased, high, score, for, the, disease, activity, index, compared, with, the, other, groups])]). relacion([sujeto(['Measurement', of, 'GATA-3-induced', cytokines, demonstrated, that, 'IL-13', was, highly]), verbo([expressed]), complemento([in, the, colon, from, 'DSS-induced', 'GATA-3', 'Tg', mice])]). relacion([sujeto(['Differentiation', of, 'CD4(+)', 'T', cells, into, type, 1, or, type, 2, subsets, is]), verbo([mediated]), complemento([by, the, expression, of, the, opposing, lineage, defining, transcription, factors, 'T-bet', and, 'GATA-3'])]). relacion([sujeto(['However,', the, existence, of, 'GATA-3(+)', 'T-bet(+)', 'CD4(+)', 'T', cells, in, mice]), verbo([suggests]), complemento([functional, plasticity, of, these, subsets])]). relacion([sujeto(['Treatment', with, recombinant, human, 'IL-12', or, expansion, of, 'IL-12-producing', human, dendritic, cells, in, vivo, reverted, this, phenotype, and]), verbo([led]), complemento([to, the, 'down-regulation', of, 'GATA-3', expression])]). relacion([sujeto(['In', 'conclusion,', our, study, shows, the, capacity, of, human, 'CD4(+)', and, 'CD8(+)', 'T', cells, for, stable, 'co-expression', of, 'GATA-3', and, 'T-bet', in, humanized, mice, and]), verbo([reveals]), complemento([a, critical, role, for, 'IL-12', in, regulating, this, phenotype])]). relacion([sujeto(['Epithelial', tumor, cells, that]), verbo([have]), complemento([undergone, 'epithelial-to-mesenchymal', transition, '(', 'EMT)', are, typically, prone, to, metastasis, and, drug, resistance, and, contribute, to, a, poor, clinical, outcome])]). relacion([sujeto(['The', transcription, factor, 'ZEB1', is, a, known, driver, of, 'EMT,', and, mediators, of, 'ZEB1', represent, potential, therapeutic]), verbo([targets]), complemento([for, metastasis, suppression])]). relacion([sujeto(['Here,', we]), verbo([have]), complemento([shown, that, phosphatidylinositol, 3, -, 'kinase-targeted', '(', 'PI3K-targeted)', therapy, suppresses, metastasis, in, a, mouse, model, of, 'Kras/Tp53-mutant', lung, adenocarcinoma, that, develops, metastatic, disease, due, to, high, expression, of, 'ZEB1'])]). relacion([sujeto(['In', lung, adenocarcinoma, cells, from, 'Kras/Tp53-mutant', animals, and, human, lung, cancer, cell, 'lines,', 'ZEB1']), verbo([activated]), complemento(['PI3K', by, derepressing, 'miR-200', 'targets,', including, amphiregulin, '(', 'AREG),', betacellulin, '(', 'BTC),', and, the, transcription, factor, 'GATA6,', which, stimulated, an, 'EGFR/ERBB2', autocrine, loop])]). relacion([sujeto(['Additionally,', 'ZEB1-dependent', derepression, of, the, 'miR-200', and, 'miR-183']), verbo([target]), complemento([friend, of, 'GATA', 2, '(', 'FOG2)', enhanced, 'GATA3-induced', expression, of, the, p110α, catalytic, subunit, of, 'PI3K'])]). relacion([sujeto(['Surprisingly,', 'FOG2', was, not]), verbo([required]), complemento([for, mesenchymal, 'differentiation,', suggesting, that, mesenchymal, differentiation, and, invasion, are, distinct, and, separable, processes])]). relacion([sujeto(['Together,', these, results, indicate, that, 'ZEB1', sensitizes, lung, adenocarcinoma, cells, to, metastasis, suppression, by, 'PI3K-targeted', therapy, and]), verbo([suggest]), complemento([that, treatments, to, selectively, modify, the, metastatic, behavior, of, mesenchymal, tumor, cells, are, feasible, and, may, be, of, clinical, value])]). relacion([sujeto(['The', transcription, factor, 'GATA3', is, a, favorable, prognostic, indicator, in, estrogen, 'receptor-α', '(', 'ERα)-positive', breast, tumors, in, which, it]), verbo([participates]), complemento([with, 'ERα', and, 'FOXA1', in, a, complex, transcriptional, regulatory, program, driving, tumor, growth])]). relacion([sujeto(['GATA3', mutations, are, frequent, in, breast, cancer, and]), verbo([have]), complemento([been, classified, as, driver, mutations])]). relacion([sujeto(['DNA']), verbo([binding]), complemento([ability, of, recombinant, 'GATA3', was, evaluated, using, electrophoretic, mobility, shift, assay, and, heparin, chromatography])]). relacion([sujeto(['The', truncated, protein, in, 'MCF7', had, impaired, interaction, with, chromatin, and, was, easily]), verbo([released]), complemento([from, the, nucleus])]). relacion([sujeto(['Recombinant', mutant, 'GATA3', was, able, to]), verbo([bind]), complemento(['DNA', to, a, lesser, degree, than, the, 'wild-type', protein])]). relacion([sujeto(['Heterozygosity', for, the, truncating, mutation]), verbo([conferred]), complemento([protection, from, regulated, turnover, of, 'GATA3,', 'ERα', and, 'FOXA1', following, estrogen, stimulation, in, 'MCF7', cells])]). relacion([sujeto(['Consistent', with]), verbo([increased]), complemento([protein, 'stability,', 'ChIP-seq', profiling, identified, greater, 'genome-wide', accumulation, of, 'GATA3', in, 'MCF7', cells, bearing, the, 'mutation,', albeit, with, a, similar, distribution, across, the, 'genome,', comparing, to, 'T47D', cells])]). relacion([sujeto(['We', propose, that, this, 'specific,', 'cancer-derived', mutation, in, 'GATA3', deregulates, physiologic, protein, 'turnover,', stabilizes, 'GATA3']), verbo([binding]), complemento([across, the, genome, and, modulates, the, response, of, breast, cancer, cells, to, estrogen, signaling])]). relacion([sujeto(['The', cholinergic, 'anti-inflammatory', pathway, can]), verbo([inhibit]), complemento([the, inflammation, of, collagen, induced, arthritis, '(', 'CIA),', a, mouse, model, of, rheumatoid, arthritis, '(', 'RA)'])]). relacion([sujeto(['However,', the, immunologic, mechanisms, that]), verbo([provide]), complemento([a, therapeutic, effect, against, the, 'auto-inflammatory', disease, are, not, yet, elucidated])]). relacion([sujeto(['The', expressions, of, 'IL-4', and, 'GATA3', were]), verbo([increased]), complemento([in, the, same, setting])]). relacion([sujeto(['Nicotine', may]), verbo([induce]), complemento([a, shift, to, the, 'Th2', lineage, and, improve, the, 'Th1/Th2', imbalance])]). relacion([sujeto(['Activating', the, cholinergic, 'anti-inflammatory', pathway, with, nicotine, can]), verbo([inhibit]), complemento(['Th17', cell, responses, and, may, improve, the, 'Th1/Th2', imbalance, in, 'CIA,', providing, a, new, justification, for, its, application, in, the, treatment, of, rheumatoid, arthritis])]). relacion([sujeto(['The', potential, mechanisms, for, their, beneficial, effects, include]), verbo([increasing]), complemento([the, number, and, function, of, 'T', regulatory, cells, '(', 'Tregs),', as, reported, in, the, local, tissue, 'post-intranasal', steroid, treatment])]). relacion([sujeto(['CRS', subjects]), verbo([reported]), complemento([improved, nasal, symptoms, '(', p, =, 0.005, ')', and, significantly, reduced, 'PB', 'Tregs', after, treatment, with, corticosteroids, '(', p, =, 0.042, ')'])]). relacion([sujeto(['In', contrast, to, prior, work, in, local, nasal, 'tissue,', our, study]), verbo([reports]), complemento([reduced, 'PB', 'Tregs', and, decreased, 'T', helper, 1, '(', 'T(H)1)', and, 'T(H)2', function, after, treatment, with, systemic, corticosteroids])]). relacion([sujeto(['These', data, indicate, that, corticosteroid, effects, on, 'Tregs', in, 'CRS', are, complex]), verbo([involving]), complemento([local, signals, in, the, tissue, that, are, distinct, from, those, in, circulating, cells])]). relacion([sujeto(['Hispanic', children]), verbo([have]), complemento([a, higher, incidence, of, acute, lymphoblastic, leukemia, '(', 'ALL)', than, 'non-Hispanic', whites, but, tend, to, be, diagnosed, at, older, ages])]). relacion([sujeto(['In', 'genome-wide', association, 'studies,', 'Native', 'American', ancestry, and, polymorphisms, in, six, genes]), verbo([have]), complemento([been, associated, with, 'ALL', risk])]). relacion([sujeto(['In', multivariable, regression, 'models,', we, investigated, whether, genomic, 'ancestry,', inherited, risk, 'SNPs,', or, acquired, somatic, alterations, were]), verbo([associated]), complemento([with, differences, in, age, at, diagnosis, in, 'Hispanic', children, with, 'B-cell', 'ALL'])]). relacion([sujeto(['Each', 20, '%']), verbo([increase]), complemento([in, 'European', ancestry, was, associated, with, a, six, month, younger, age, at, diagnosis, '(', 95, '%', 'CI', =, 0.36, -, 11.6, 'months,', 'P', =, 0.037, ')'])]). relacion([sujeto(['Correspondingly,', each, 20, '%']), verbo([increase]), complemento([in, 'Native', 'American', ancestry, was, associated, with, a, 'six-month', older, age, at, diagnosis, '(', 'P', =, 0.037, ')'])]). relacion([sujeto(['Both', the, 'TEL-AML1', translocation, and, 'high-hyperdiploidy', were]), verbo([associated]), complemento([with, younger, age, at, diagnosis, '(', 24.4, 'months,', 'P', =, 2.0, x, 10, '(', -, 4, ')', and, 12.4, 'months,', 'P', =, 0.011, ',', 'respectively),', while, 'CDKN2A', and, 'IKZF1', deletions, were, associated, with, older, age, at, diagnosis, '(', 19.7, 'months,', 'P', =, 7.0, x, 10, '(', -, 4, ')', and, 18.1, 'months,', 'P', =, 0.012, ',', 'respectively)'])]). relacion([sujeto(['Because', younger, age, at, diagnosis, is]), verbo([associated]), complemento([with, improved, treatment, outcomes, for, children, with, 'ALL,', the, effect, of, 'European', ancestry, on, 'ALL', survival, may, be, mediated, by, its, effect, on, age, at, 'diagnosis,', or, by, 'proxy,', its, association, with, more, treatable, molecular, subtypes, of, 'ALL'])]). relacion([sujeto(['The', 'GATA']), verbo([binding]), complemento([protein, 3, '(', 'GATA3)', is, a, member, of, a, family, of, 6, 'GATA', dual, zinc, finger, transcription, factors, '(', 'GATA1-6),', which, are, required, for, the, development, and, morphogenesis, of, the, mammary, gland])]). relacion([sujeto(['GATA3', is, considered, to, play, a, dual, role, in, oncogenesis, and, cancer, 'development,', whereas, somatic, 'GATA3', mutations]), verbo([have]), complemento([been, reported, in, breast, cancer])]). relacion([sujeto(['Variants', of, the, 'GATA3', genetic, 3, '\'', untranslated, region, '(', 3, '\'', 'UTR)', microRNA, '(', 'miRNA)']), verbo([binding]), complemento([sites, have, been, associated, with, breast, cancer, risk])]). relacion([sujeto(['However,', the, roles, of, genetic, variants, in, the, 'GATA3', gene, 3, '\'', 'UTR', and, its, 'post-transcriptional', regulation]), verbo([have]), complemento([not, been, fully, elucidated])]). relacion([sujeto(['We', discovered, that, rs1058240, in, the, 'GATA3', 3, '\'', 'UTR', displayed, potential, miRNA]), verbo([binding]), complemento([sites, and, this, variant, was, found, to, be, significantly, associated, with, 'GATA3', mRNA, expression, '(', 'P=2'])]). relacion([sujeto([3.6e-6, ')', ',']), verbo([suggesting]), complemento([that, rs1058240, may, be, a, putative, variant, mediating, the, 'post-transcriptional', regulation, of, the, 'GATA3', target, gene])]). relacion([sujeto(['Further', studies, investigating, the, regulatory, mechanism, of, 'GATA3', transcriptional, activity, are]), verbo([required]), complemento([to, design, novel, strategies, against, breast, cancer, cell, growth, and, differentiation])]). relacion([sujeto(['Current', markers, of, diagnostic, utility, include, p63, and, cytokeratin, 5, /, 6, ;, 'however,', their, expression]), verbo([has]), complemento([been, demonstrated, in, 11, '%', to, 22, '%', and, 27, '%', of, cutaneous, 'metastases,', respectively])]). relacion([sujeto(['Furthermore,', the, immunoreactivity, of, p40, and, 'GATA3', in, various, cutaneous, adnexal, carcinomas]), verbo([has]), complemento([not, been, previously, reported])]). relacion([sujeto(['In', 'summary,', while, p63, and, cytokeratin, 5, /, 6]), verbo([have]), complemento([similar, sensitivity, '(', 84, '%', and, 86, '%', ',', 'respectively)', in, detecting, primary, adnexal, 'carcinomas,', p40, appeared, to, be, the, most, specific, marker, '(', 92, '%', ')', with, the, best, positive, predictive, value, '(', 90, '%', ')'])]). relacion([sujeto(['GATA']), verbo([binding]), complemento([protein, 3, '(', 'GATA-3)', is, a, novel, immunohistochemical, marker, for, urothelial, carcinoma, '(', 'UC);', 'however,', few, studies, have, investigated, 'GATA-3\'s', role, as, a, marker, for, 'UC', variants])]). relacion([sujeto(['However,', the, 'GATA-3', expression, levels, of, the, sarcomatoid, variants, '(', 16, '%', ;, 7, /, 43, ')', and, small, cell, carcinoma, variants, '(', 5, '%', ;, 1, /, 22, ')', ',', which, only, weakly]), verbo([expressed]), complemento([the, 'protein,', were, significantly, lower, than, that, of, conventional, 'UC', '(', 'P', &, 'lt;'])]). relacion([sujeto(['Only', 7, '%', of, squamous, cell, carcinomas, '(', 1, /, 14, ')']), verbo([expressed]), complemento(['GATA-3,', and, it, was, also, significantly, lower, than, that, of, conventional, 'UC', '(', 'P', &, 'lt;'])]). relacion([sujeto(['GATA-3', expression, was, not, significantly]), verbo([associated]), complemento([with, tumor, stage, or, 'patients\'', clinical, outcomes])]). relacion([sujeto(['Dietary', 'factors,', including, 'meat,', 'fruits,', vegetables, and, 'fiber,', are]), verbo([associated]), complemento([with, colorectal, 'cancer;', 'however,', there, is, limited, information, as, to, whether, these, dietary, factors, interact, with, genetic, variants, to, modify, risk, of, colorectal, cancer])]). relacion([sujeto(['We', used, logistic, regression, to, investigate, multiplicative, 'gene-diet', 'interactions,', as, well, as, our, recently, developed, 'Cocktail', method, that]), verbo([involves]), complemento([a, screening, step, based, on, marginal, associations, and, 'gene-diet', correlations, and, a, testing, step, for, multiplicative, 'interactions,', while, correcting, for, multiple, testing, using, weighted, hypothesis, testing])]). relacion([sujeto(['Per', quartile, increment, in, the, intake, of, red, and, processed, meat, were]), verbo([associated]), complemento([with, statistically, significant, increased, risks, of, colorectal, cancer, and, 'vegetable,', fruit, and, fiber, intake, with, lower, risks])]). relacion([sujeto(['The', risk, of, colorectal, cancer]), verbo([associated]), complemento([with, processed, meat, was, increased, among, individuals, with, the, 'rs4143094-TG', and, -, 'TT', genotypes, '(', 'OR', =, 1.2, and, 'OR', =, 1.39, ',', 'respectively)', and, null, among, those, with, the, 'GG', genotype, '(', 'OR', =, 1.03, ')'])]). relacion([sujeto(['Our', results, identify, a, novel, 'gene-diet', interaction, with, processed, meat, for, colorectal, 'cancer,', highlighting, that, diet, may, modify, the, effect, of, genetic, variants, on, disease, 'risk,', which, may]), verbo([have]), complemento([important, implications, for, prevention])]). relacion([sujeto(['Newly', identified, nuocytes, or, group, 2, innate, lymphoid, cells, '(', 'ILC2s)', play, an, important, role, in, 'Th2', cell]), verbo([mediated]), complemento([immunity, such, as, protective, immune, responses, to, helminth, 'parasites,', allergic, 'asthma,', and, chronic, rhinosinusitis])]). relacion([sujeto(['Our', previous, study]), verbo([found]), complemento([that, there, was, a, predominant, 'Th2', phenotype, in, patients, with, gastric, cancer])]). relacion([sujeto(['The', expression, levels, of, 'RORα,', 'GATA3,', 'T1/ST2,', 'IL-17RB,', 'CRTH2,', 'IL-33,', 'IL-5,', and, 'IL-4', mRNA, were, significantly]), verbo([increased]), complemento([in, 'patients,', but, no, significant, changes, were, found, in, 'ICOS,', 'CD45,', and, 'IL-13', 'expression,', and, there, was, a, positive, correlation, between, 'RORα', or, 'IL-13', and, other, related, 'factors,', such, as, 'ICOS', and, 'CD45'])]). relacion([sujeto(['The']), verbo([increased]), complemento([frequency, of, 'ILC2s', was, also, found, in, 'PBMC', of, patients, by, flow, cytometry])]). relacion([sujeto(['In', 'addition,', the, mRNA, of, 'Arg1', and, iNOS, were, also, significantly]), verbo([increased]), complemento([in, patients])]). relacion([sujeto(['These', results]), verbo([suggested]), complemento([that, there, are, polarized, 'ILC2s', in, gastric, cancer, patients, which, might, contribute, to, immunosuppressive, microenvironment, and, closely, related, to, the, upregulation, of, 'MDSCs', and, 'M2', macrophages])]). relacion([sujeto(['Although', the, involvement, of, helper, 'T', '(', 'Th)', and, regulatory, 'T', '(', 'Treg)', 'cell-related', immune, molecules, in, pathogenesis, of, inflammatory, bowel, disease, '(', 'IBD)', is, widely, 'accepted,', no, discriminatory, mucosal, expression, profiles, of, these, molecules, between, ulcerative, colitis, '(', 'UC)', and, 'Crohn\'s', disease, '(', 'CD)']), verbo([have]), complemento([been, clarified])]). relacion([sujeto(['By', univariate, 'analysis,', many]), verbo([targets]), complemento([were, markedly, increased, in, inflamed, versus, noninflamed, areas])]). relacion([sujeto(['Genetic', effects, on, asthma, of, genes, in, the, 'T-helper', 2, '(', 'Th2)', pathway, may]), verbo([interact]), complemento([with, epigenetic, factors, including, 'DNA', methylation])]). relacion([sujeto(['At', age, 10, ',', the, odds, of, asthma, tended, to]), verbo([decrease]), complemento([as, cg12405139, '(', 'GATA3)', methylation, increased, '(', 'log-OR', =, -, 12.15, ;, 'P', =, 0.049, ')', ;, this, effect, disappeared, by, age, 18])]). relacion([sujeto(['At', age, 18, ',', methylation, of, cg09791102, '(', 'IL4R)', was]), verbo([associated]), complemento([with, higher, risk, of, asthma, among, subjects, with, genotype, 'GG', compared, to, 'AG', '(', 'P', =, 0.003, ')', ',', increased, cg26937798, methylation, among, subjects, with, rs3024685, '(', 'IL4R)', genotype, 'AA', '(', 'P', =, 0.003, ')', or, rs8832, '(', 'IL4R)', genotype, 'GG', '(', 'P', =, 0.01, ')', was, associated, with, a, lower, asthma, 'risk;', these, 'CpGs', had, no, effect, at, age, 10])]). relacion([sujeto(['Increasing', cg26937798, methylation, over, time, possibly, reduced, the, risk, of, positive, asthma, transition, '(', 'asthma-free', at, age, 10, '→', asthma, at, age, 18, ;, 'log-OR', =, -, 3.11, ;, 'P', =, 0.069, ')', and]), verbo([increased]), complemento([the, likelihood, of, negative, transition, '(', asthma, at, age, 10, '→', 'asthma-free', at, age, 18, ;, 'log-OR', =, 3.97, ;, 'P', =, 0.074, ')'])]). relacion([sujeto(['Nucleocytoplasmic', shuttling, of, macromolecules, is, a, 'well-controlled', process]), verbo([involving]), complemento([importins, and, exportins])]). relacion([sujeto(['These', karyopherins]), verbo([recognize]), complemento([and, bind, to, 'receptor-mediated', intracellular, signals, through, specific, signal, sequences, that, are, present, on, cargo, proteins, and, transport, into, and, out, of, the, nucleus, through, nuclear, pore, complexes])]). relacion([sujeto(['Nuclear', localization, signals, '(', 'NLS)', present, on, cargo, molecules, to, be, imported, while]), verbo([nuclear]), complemento([export, signals, '(', 'NES)', on, the, molecules, to, be, exported, are, recognized, by, importins, and, 'exportins,', respectively])]). relacion([sujeto(['The', classical, 'NLS', are]), verbo([found]), complemento([on, many, transcription, factors, and, molecules, that, are, involved, in, the, pathogenesis, of, allergic, diseases])]). relacion([sujeto(['In', 'addition,', several, immune, 'modulators,', including, corticosteroids, and, vitamin, 'D,', elicit, their, cellular, responses, by]), verbo([regulating]), complemento([the, expression, and, activity, of, importin, molecules])]). relacion([sujeto(['In', this, review, 'article,', we]), verbo([provide]), complemento([a, comprehensive, list, of, importin, and, exportin, molecules, and, their, specific, cargo, that, shuttled, between, cytoplasm, and, the, nucleus])]). relacion([sujeto(['We', also, critically, review, the, role, and, regulation, of, specific, importin, and, exportin]), verbo([involved]), complemento([in, the, transport, of, activated, transcription, factors, in, allergic, 'diseases,', the, underlying, molecular, 'mechanisms,', and, the, potential, target, sites, for, developing, better, therapeutic, approaches])]). relacion([sujeto(['Innate', lymphoid, cells, '(', 'ILCs)', are, a, recently]), verbo([recognized]), complemento([group, of, lymphocytes, that, have, important, functions, in, protecting, epithelial, barriers, against, infections, and, in, maintaining, organ, homeostasis])]). relacion([sujeto(['ILCs']), verbo([have]), complemento([been, categorized, into, three, distinct, 'groups,', transcriptional, circuitry, and, effector, functions, of, which, strikingly, resemble, the, various, 'T', helper, cell, subsets])]). relacion([sujeto(['Interestingly,', the, 'CHILP', differentiated, into, 'ILC2', and, 'ILC3', 'lineages,', but, not, into, conventional, natural, killer, '(', 'cNK)', cells, that]), verbo([have]), complemento([been, considered, an, 'ILC1', subset])]). relacion([sujeto(['Instead,', the, 'CHILP', gave, rise, to, a, peculiar, 'NKp46(+)', 'IL-7Rα(+)', 'ILC', lineage, that]), verbo([required]), complemento(['T-bet', for, specification, and, was, distinct, of, cNK, cells, or, other, 'ILC', lineages])]). relacion([sujeto(['Although', mast, cells, play, a, critical, role, in, allergic, 'reactions,', the, cells, are, also]), verbo([involved]), complemento([in, the, protective, immunity, in, the, body])]). relacion([sujeto(['Mast', 'cell-derived', mouse, mast, cell, 'protease-6']), verbo([increased]), complemento([the, expression, of, 'Bcl-6', in, 'Th2', cells])]). relacion([sujeto(['Bcl-6']), verbo([inhibited]), complemento([the, expression, of, 'GATA-3', in, 'Th2', 'cells,', 'subsequently,', forkhead, box, 'P3', was, increased, and, the, 'Th2', cytokines, were, reduced, in, the, 'cells;', the, cells, thus, showed, the, immune, regulatory, properties, similar, to, regulatory, 'T', cells])]). relacion([sujeto(['PTEN', nonsense, mutations]), verbo([associated]), complemento([with, 'sig-', nificantly, shorter, 'disease-free', survival, and, overexpression, of, 'PTEN', protein, linked, to, shorter, 'disease-free', and, overall, survival, of, patients, with, 'GBM'])]). relacion([sujeto(['PTEN', nonsense, mutations, correlated, with]), verbo([decreased]), complemento([p53, and, 'Gata3', protein, levels, and, increased, genomic, instability, in, human, 'GBM', tissues])]). relacion([sujeto(['Expression', of, nonsense, 'PTEN', mutant]), verbo([decreased]), complemento([p53, and, 'Gata3', 'levels,', producing, increased, 'DNA', damage, both, in, vitro, and, in, vivo])]). relacion([sujeto(['The', 'CD4(+)', 'T-cell', subgroups, play, central, pathophysiological, roles, in, 'Crohn\'s', disease, '(', 'CD);', 'however,', their, clinical, relevance]), verbo([requires]), complemento([additional, clarification, and, remains, controversial])]). relacion([sujeto(['Imbalances', among, 'Treg,', 'Th1,', and, 'Th17', subgroups, were]), verbo([found]), complemento([in, 'Chinese', 'CD', patients])]). relacion([sujeto(['Treg/Th1', and, 'Treg/Th17', ratios, are]), verbo([associated]), complemento([with, disease, activity, and, are, potential, prognostic, indicators, for, predicting, 'CD', recurrence])]). relacion([sujeto(['GATA-binding', protein, 3, '(', 'GATA-3)']), verbo([has]), complemento([emerged, recently, as, a, sensitive, and, relatively, specific, immunomarker, for, breast, and, urothelial, 'carcinomas,', but, the, data, documenting, its, expression, in, 'ER-negative', breast, carcinomas, are, 'limited;', this, often, poses, a, dilemma, in, the, setting, of, metastases])]). relacion([sujeto(['Overall,', 69, '%', '(', 66, /, 96, ')', ',', 15, '%', '(', 14, /, 96, ')', ',', and, 35, '%', '(', 34, /, 96, ')', of, 'ER-negative', breast, carcinomas]), verbo([expressed]), complemento(['GATA-3,', 'GCDFP-15,', and, 'MGB,', respectively])]). relacion([sujeto(['Our', data]), verbo([suggest]), complemento([that, 'GATA-3', 'is,', so, 'far,', the, best, 'breast-specific', 'immunomarker,', especially, when, encountering, 'ER-negative', metastatic, breast, carcinomas])]). relacion([sujeto(['GATA3', '(', 'GATA-binding', protein, 3, ')', expression, in, urothelial, carcinoma, '(', 'UC)', and, mammary, carcinomas]), verbo([has]), complemento([been, recently, reported])]). relacion([sujeto(['Delta', 'Np63', '(', 'p40)']), verbo([has]), complemento([been, shown, to, be, expressed, highly, selectively, in, squamous, cell, carcinomas, '(', 'SCCs)', but, the, literature, concerning, the, expression, of, p40, in, 'UC', is, limited, and, controversial])]). relacion([sujeto(['Thirty-two', 'MUC', cytology, cases, and, 44, controls, '(', 22, 'UC', cases, and, 22, 'SCC', 'cases)', were, stained, for, 'GATA3,', 'p40,', and, p63, and]), verbo([nuclear]), complemento([staining, intensity, and, the, percentage, of, positive, cells, were, recorded, and, compared])]). relacion([sujeto([1, ')', ',', but, 'GATA3', positivity, was, not]), verbo([found]), complemento([to, be, significantly, different, from, 'UC', controls, '(', 90.91, '%', ')', '(', 'P', =])]). relacion([sujeto([p63, positivity, was]), verbo([found]), complemento([to, be, significantly, lower, in, 'MUC', cases, compared, with, 'UC', controls, '(', 95.45, '%', ')', and, 'SCC', controls, '(', 95.45, '%', ')', '(', 'P<'])]). relacion([sujeto(['Curcumin,', a, natural, product, derived, from, the, plant, 'Curcuma', 'longa,']), verbo([has]), complemento([been, found, to, have, 'anti-inflammatory,', antineoplastic, and, antifibrosis, effects])]). relacion([sujeto(['It']), verbo([has]), complemento([been, reported, that, curcumin, attenuates, allergic, airway, inflammation, in, mice, through, inhibiting, 'NF-κB', and, its, downstream, transcription, factor, 'GATA3'])]). relacion([sujeto(['It', also]), verbo([has]), complemento([been, proved, the, antineoplastic, effect, of, curcumin, through, 'down-regulating', 'Notch1', receptor, and, its, downstream, nuclear, transcription, factor, 'NF-κB', levels])]). relacion([sujeto(['Our', findings, showed, that, the, levels, of, 'Notch1', and, 'Notch2', receptors, were, 'up-regulated', in, asthma, 'group,', accompanied, by, the]), verbo([increased]), complemento([expression, of, 'GATA3'])]). relacion([sujeto(['Curcumin', pretreatment, improved, the, airway, inflammatory, cells, infiltration, and, reversed, the]), verbo([increasing]), complemento([levels, of, 'Notch1/2', receptors, and, 'GATA3'])]). relacion([sujeto(['Notch3', receptor, was, not]), verbo([expressed]), complemento([in, all, of, the, four, groups])]). relacion([sujeto(['The', results, of, the, present, study]), verbo([suggested]), complemento([that, 'Notch1', and, 'Notch2', 'receptor,', major, 'Notch1', 'receptor,', played, an, important, role, in, the, development, of, allergic, airway, inflammation, and, the, inhibition, of, 'Notch1-GATA3', signaling, pathway, by, curcumin, can, prevent, the, development, and, deterioration, of, the, allergic, airway, inflammation])]). relacion([sujeto(['The', prevalence, of, allergic, asthma]), verbo([has]), complemento([been, increased, rapidly, in, recent, years])]). relacion([sujeto(['About', 20, '%', of, all, these, sufferers]), verbo([have]), complemento([experienced, asthma, exacerbation])]). relacion([sujeto(['BuShenYiQi', 'Formula', '(', 'BSYQF)']), verbo([has]), complemento([been, widely, used, to, treat, bronchial, asthma, and, its, exacerbation, for, decades, in, 'Huashan', 'Hospital', of, 'Fudan', 'University,', 'China'])]). relacion([sujeto(['BSYQF', significantly, attenuated, airway, hyperresponsiveness, and]), verbo([inhibited]), complemento([inflammatory, cell, 'infiltration,', especially, for, excessive, infiltration, of, eosinophils, and, neutrophils])]). relacion([sujeto(['Histopathological', analysis, showed, that, 'BSYQF', could]), verbo([suppress]), complemento([airway, inflammation, and, 'RSV', replication])]). relacion([sujeto(['The']), verbo([decreases]), complemento([of, 'antigen-specific', 'IgE,', 'IL-4,', 'IL-5,', 'IL-6,', 'IL-17a', and, increases, of, 'IFN-γ,', 'IL-12', were, observed, in, 'BALF,', lung, homogenate, or, serum, after, 'BSYQF', treatment])]). relacion([sujeto(['And', as, a, result, of, strengthened, 'Th1-response,']), verbo([activated]), complemento([macrophages, were, also, observed, by, remarkable, enhancement, of, signature, gene, expressions, and, phagocytosis])]). relacion([sujeto(['These', effects, may, be]), verbo([mediated]), complemento([at, least, partially, by, regulating, the, balance, between, 'Th1', and, 'Th2-Th17', responses])]). relacion([sujeto(['Fifty', percentage, of, subjects]), verbo([reported]), complemento(['allergy,', 59, '%', had, '≥1', nasopharyngeal, 'viruses,', and, 24, '%', had, '≥1', intratonsillar, viruses])]). relacion([sujeto(['IL-37', expression, was, positively]), verbo([associated]), complemento([with, atopic, 'dermatitis,', whereas, 'IFN-α,', 'IL-13,', 'IL-28,', and, 'Tbet', expressions, were, negatively, associated, with, allergic, diseases])]). relacion([sujeto(['Abnormalities', in, pyloric, development, or, in, contractile, function, of, the, pylorus]), verbo([cause]), complemento([reflux, of, duodenal, contents, into, the, stomach, and, increase, the, risk, of, gastric, metaplasia, and, cancer])]). relacion([sujeto(['Examination', of, 'Isl1', expression, in, developing, mouse, stomach, by, 'immunohistochemistry,', whole, mount, in, situ, hybridization, and, 'real-time', quantitative, 'PCR', demonstrated, that, 'Isl1', is, highly]), verbo([expressed]), complemento([in, developing, mouse, 'stomach,', principally, in, the, smooth, muscle, layer, of, the, pylorus])]). relacion([sujeto(['Isl1', expression, was, also, examined, by, immunofluorescence, in, human, hypertrophic, pyloric, stenosis, where, the, majority, of, smooth, muscle, cells, were]), verbo([found]), complemento([to, express, 'Isl1'])]). relacion([sujeto(['Isl1', deficiency]), verbo([led]), complemento([to, nearly, complete, absence, of, the, pyloric, outer, longitudinal, muscle, layer, at, embryonic, day, 18.5, ',', which, is, consistent, with, 'Gata3', null, mouse, phenotype])]). relacion([sujeto(['Chromatin', 'immunoprecipitation,', luciferase, 'assays,', and, electrophoretic, mobility, shift, assays, revealed, that, 'Isl1']), verbo([ensures]), complemento([normal, pyloric, development, by, directly, targeting, 'Gata3'])]). relacion([sujeto(['These', findings, are, highly, clinically, relevant, and, may, help, to, better, understand, pathways]), verbo([leading]), complemento([to, pyloric, disease])]). relacion([sujeto(['Transfusion', was]), verbo([associated]), complemento([with, a, greater, immediate, rise, in, 'IL-10', '(', 'P', =, 0.003, ')', and, 'IL-27', '(', 'P', =, 0.04, ')', mRNA, levels])]). relacion([sujeto(['There', were, greater, reductions, in, 'T-bet', '(', 'P', =, 0.03, ')', mRNA, levels, and, lesser]), verbo([increases]), complemento([in, 'TNFα', '(', 'P', =, 0.015, ')', and, 'IFNγ', '(', 'P', =, 0.035, ')', at, 24, hours, in, those, transfused])]). relacion([sujeto(['Multiple', regression, models, confirmed, that, the, transfusion, of, blood, products, was, independently]), verbo([associated]), complemento([with, altered, patterns, of, gene, expression])]). relacion([sujeto(['Furthermore,', transfusion, was]), verbo([associated]), complemento([with, an, increased, susceptibility, to, nosocomial, infections])]). relacion([sujeto(['The', immune]), verbo([mediated]), complemento([hematopoietic, inhibition, is, recognized, as, the, most, common, pathogenesis, of, 'AA'])]). relacion([sujeto(['Experimental', samples, were, obtained, from, 27, patients, with, 'AA,', including, 15, cases, of, severe, 'AA', '(', 'SAA)', and, 12, cases, of, immune]), verbo([mediated]), complemento(['AA', '(', 'MAA),', and, 25, healthy, volunteers, '(', control, 'group)'])]). relacion([sujeto(['Compared', to, the, healthy, control, 'group,', the, expression, of, 'T-bet', mRNA, and, the, percentage, of, 'Th1-type', cells, in, the, 'AA', group, significantly]), verbo([increased]), complemento(['(', p, &, 'lt;', 0.01, ')', ',', while, the, expression, of, 'GATA-3', and, 'FoxP3', mRNA, and, the, percentage, of, 'Th2-type', cells, decreased, sharply, '(', p, &, 'lt;', 0.05, ',', p, &, 'lt;', 0.01, ')'])]). relacion([sujeto(['Compared', with, 'MAA,', the, expression, of, 'T-bet', mRNA, and, the, percentage, of, 'Th1-type', cells]), verbo([increased]), complemento([significantly, in, 'SAA', '(', p, &, 'lt;', 0.01, ')', ;, 'meanwhile,', the, expression, of, 'GATA-3', mRNA, and, the, proportion, of, 'Th2-type', cells, decreased, noticeably, '(', p, &, 'lt;', 0.05, ',', p, &, 'lt;', 0.01, ')'])]). relacion([sujeto(['Particularly,', the, percentage, of, 'CD3+', and, 'CD3+CD8+', 'T', cells, in, the, 'AA', group]), verbo([increased]), complemento(['(', p, &, 'lt;', 0.05, ')', ',', while, the, percentage, of, 'CD3+CD4+,', 'CD4+CD25+,', and, 'CD4+CD8+', cells, decreased, '(', p, &, 'lt;', 0.05, ',', p, &, 'lt;', 0.01, ')'])]). relacion([sujeto(['Abnormal', expression, of, the, transcription, factors, 'T-bet', and, 'GATA-3', contributes, to, the, imbalance, of, 'Thl/Th2', lymphocytes]), verbo([associated]), complemento([with, immune, 'dysfunction,', leading, to, the, development, and, progression, of, 'AA'])]). relacion([sujeto(['This', variant, is]), verbo([reported]), complemento([with, clinicopathological, correlations, and, immunohistochemical, findings])]). relacion([sujeto(['However,', the, role, of, 'CD39', in, allergic, asthma]), verbo([has]), complemento([not, been, fully, elucidated])]). relacion([sujeto(['These', data]), verbo([suggested]), complemento([that, 'CD39', mRNA, expression, was, downregulated, in, allergic, 'asthma,', which, was, positively, correlated, with, serum, 'IL-4,', 'IL-17A', and, 'GATA3', expression, and, negatively, correlated, with, serum, 'TGF-β', and, 'FoxP3', 'expression,', whereas, there, was, no, correlation, with, 'ROR-γt'])]). relacion([sujeto(['Therefore,', it, was, hypothesized, that, 'CD39', may]), verbo([participate]), complemento([in, the, occurrence, and, progression, of, allergic, asthma])]). relacion([sujeto(['We', examined, the, 'GATA2', expression, pattern, in, the, adult, kidney, by, tracing, green, fluorescent, protein, '(', 'GFP)', fluorescence, in, 'Gata2(GFP/+)', mice, that, recapitulate, endogenous, 'GATA2', expression, and]), verbo([found]), complemento([a, robust, 'GFP', expression, specifically, in, the, renal, medulla])]). relacion([sujeto(['Upon', purification, of, the, 'GFP-positive', 'cells,', we]), verbo([found]), complemento([that, collecting, duct, '(', 'CD)-specific', 'markers,', including, aquaporin, 2, '(', 'Aqp2),', an, important, channel, for, water, reabsorption, from, 'urine,', were, abundantly, expressed])]). relacion([sujeto(['We']), verbo([found]), complemento([that, the, 'Gata2-CKO', mice, showed, a, significant, decrease, in, 'Aqp2', expression])]). relacion([sujeto(['We', introduced, 'biotin-tagged', 'GATA2', into, a, mouse, 'CD-derived', cell, line, and, conducted, chromatin, pulldown, 'assays,', which, revealed, direct, 'GATA2']), verbo([binding]), complemento([to, conserved, 'GATA', motifs, in, the, 'Aqp2', promoter, region])]). relacion([sujeto(['A', luciferase, reporter, assay, using, an, 'Aqp2', 'promoter-reporter', showed, that, 'GATA2', trans]), verbo([activates]), complemento(['Aqp2', through, the, 'GATA', motifs])]). relacion([sujeto(['These', results, demonstrate, that, 'GATA2']), verbo([regulates]), complemento([the, 'Aqp2', gene, expression, in, 'CD', cells, and, contributes, to, the, maintenance, of, the, body, water, homeostasis])]). relacion([sujeto(['The', epidermis, is]), verbo([maintained]), complemento([by, epidermal, stem, cells, '(', 'ESCs)', that, reside, in, distinct, niches, and, contribute, to, homeostasis, and, wound, closure])]). relacion([sujeto(['Keratinocytes', at, the, nonhealing, edges, of, venous, ulcers, '(', 'VUs)', are, 'healing-incompetent,', 'hyperproliferative,', and, 'nonmigratory,']), verbo([suggesting]), complemento([deregulation, of, 'ESCs'])]). relacion([sujeto(['To', 'date,', genes, which]), verbo([regulate]), complemento(['ESC', niches, have, been, studied, in, mice, only])]). relacion([sujeto(['In', a, prospective, clinical, study, of, 10, 'VUs,', we, confirmed, suppression, of, the, bone, morphogenetic, protein, receptor, '(', 'BMPR)', and, 'GATA']), verbo([binding]), complemento([protein, 3, '(', 'GATA3)', as, well, as, inhibitors, of, 'DNA-binding', proteins, 2, and, 4, '(', 'ID2', and, 'ID4)'])]). relacion([sujeto(['We', also]), verbo([found]), complemento([decreased, levels, of, phosphorylated, glycogen, synthase, kinase, 3, '(', 'GSK3),', nuclear, presence, of, 'β-catenin,', and, overexpression, of, its, transcriptional, 'target,', 'c-myc,', indicating, activation, of, the, 'Wnt', pathway])]). relacion([sujeto(['Additionally,', we]), verbo([found]), complemento(['down-regulation', of, 'leucine-rich', repeats, and, 'immunoglobulin-like', domains, protein, 1, '(', 'LRIG1),', a, gene, important, for, maintaining, 'ESCs', in, a, quiescent, 'state,', and, absence, of, keratin, 15, '(', 'K15),', a, marker, of, the, basal, stem, cell, compartment, suggesting, local, depletion, of, 'ESCs'])]). relacion([sujeto(['Our', study, shows, that]), verbo([loss]), complemento([of, genes, important, for, regulation, of, 'ESCs', and, their, fate, along, with, activation, of, 'β-catenin', and, 'c-myc', in, the, 'VU', may, contribute, to, 'ESC', deprivation, and, a, 'hyperproliferative,', nonmigratory, healing, incapable, wound, edge])]). relacion([sujeto(['The', 'GATA3', subgroup, was, significantly]), verbo([associated]), complemento([with, poor, overall, survival, '(', 'P', =])]). relacion([sujeto(['In', 'AITL,', high, expression, of, several, signatures]), verbo([associated]), complemento([with, the, tumor, microenvironment, was, significantly, associated, with, outcome])]). relacion([sujeto(['Prostate-specific', 'antigen,', 'prostate-specific', acid, 'phosphatase,', 'prostate-specific', membrane, 'antigen,', prostein, '(', 'P501S),', 'alpha-methylacyl-CoA', 'racemase,', and, 'GATA']), verbo([binding]), complemento([protein, 3, '(', 'GATA3)', were, 'negative;', 'p63,', 34, 'betaE12,', cytokeratin, 5, /, 6, ',', and, p53, were, positive, in, cells, in, basal, and, suprabasal, 'positions,', whereas, 'CA-125', was, expressed, in, the, luminal, cells])]). relacion([sujeto(['To', the, best, of, our, 'knowledge,', there, are, no, previous]), verbo([reports]), complemento([of, such, a, change, in, a, human, 'SV'])]). relacion([sujeto(['Here,', we]), verbo([report]), complemento([that, 'GATA3', was, indispensable, for, the, development, of, all, 'IL-7Rα(+)', 'ILC', subsets, and, 'T', cells, but, was, not, required, for, the, development, of, classical, natural, killer, cells])]). relacion([sujeto(['Genome-wide', gene, expression, analyses, indicated, that, 'GATA3']), verbo([regulated]), complemento([a, similar, set, of, cytokines, and, receptors, in, 'Th2', cells, and, 'ILC2s,', but, not, in, 'ILC3s'])]). relacion([sujeto(['Thus,', 'GATA3', plays, parallel, roles, in]), verbo([regulating]), complemento([the, development, and, functions, of, 'CD4(+)', 'T', cells, and, 'IL-7Rα(+)', 'ILCs'])]). relacion([sujeto(['To']), verbo([report]), complemento([the, auditory, and, vestibular, phenotypes, of, patients, with, 'GATA3', mutation])]). relacion([sujeto(['Patients', '(', 29, -, 60, yr, 'old;', mean, 'age,', 42.5, 'yr;', 3, male, and, 3, female, 'subjects)', were, confirmed, to]), verbo([have]), complemento([heterozygous, mutations, involving, 'GATA3', by, 'Sanger', sequencing])]). relacion([sujeto(['All', patients, with, 'GATA3', mutation, presented, with, hearing]), verbo([loss]), complemento([during, childhood])]). relacion([sujeto(['ABRs', were, remarkably, robust, and]), verbo([provided]), complemento([no, evidence, of, retrocochlear, dysfunction])]). relacion([sujeto(['Patients', with, 'GATA3', mutation, present, with, 'early-onset', sensorineural, hearing]), verbo([loss]), complemento(['(', 'SNHL)'])]). relacion([sujeto(['The', majority, of, the, genetic, component, to, disease, susceptibility]), verbo([has]), complemento([yet, to, be, accounted, for])]). relacion([sujeto(['Meta-analysis', was, used, to, compare, genotype, frequencies, between, the]), verbo([participating]), complemento(['centres,', allowing, for, heterogeneity])]). relacion([sujeto(['We']), verbo([report]), complemento([significant, association, with, alleles, of, two, 'STAT4', markers, in, 'AAD', cohorts, '(', 'rs4274624:', 'P', =, 0.00016, ;, 'rs10931481:', 'P', =, 0.0007, ')'])]). relacion([sujeto(['In', 'addition,', nominal, association, of, 'AAD', with, alleles, at, 'GATA3', was]), verbo([found]), complemento([in, 3, patient, cohorts, and, supported, by, 'meta-analysis'])]). relacion([sujeto(['Finally,', nominal, association, was]), verbo([found]), complemento([at, 'SNPs', in, both, the, 'NF-κB1', and, 'IL23A', genes, in, the, 'UK', and, 'Italian', cohorts, respectively])]). relacion([sujeto(['Variants', in, the, 'STAT4', 'gene,', previously]), verbo([associated]), complemento([with, other, autoimmune, 'conditions,', confer, susceptibility, to, 'AAD'])]). relacion([sujeto(['Additionally,', we]), verbo([report]), complemento([association, of, 'GATA3', variants, with, 'AAD:', this, adds, to, the, recent, report, of, association, of, 'GATA3', variants, with, rheumatoid, arthritis])]). relacion([sujeto(['These', cells, exhibited, alkaline, phosphatase, '(', 'AP)', activity, and]), verbo([expressed]), complemento([pluripotency, 'markers,', such, as, 'OCT4,', 'NANOG,', 'SOX2,', 'SSEA-1,', 'SSEA-4,', 'TRA-1-60,', and, 'TRA-1-81,', and, 'TR', lineage, markers, such, as, 'CDX2,', as, determined, by, both, immunofluorescence, and, reverse, 'transcription-polymerase', chain, reaction, '(', 'RT-PCR)'])]). relacion([sujeto(['We']), verbo([report]), complemento([a, case, of, adenocarcinoma, of, the, paraurethral, glands, in, a, 56, -, 'year-old', 'woman,', presenting, with, abnormal, serous, vaginal, discharges])]). relacion([sujeto(['The', absence, of, modifications, such, as, urethritis, cystic, glandularis, on, the, urethral, 'mucosa,', as, well, as, the, lack, of, a, lesion, in, 'situ,']), verbo([associated]), complemento([with, the, immunohistochemical, expression, of, 'PAX8', and, negativity, for, 'GATA3', and, 'S100p,', suggested, that, the, adenocarcinoma, originated, from, the, paraurethral, glands, rather, than, from, the, urethral, mucosa])]). relacion([sujeto(['Invasive', micropapillary, carcinomas]), verbo([have]), complemento([been, characterized, as, a, rare, distinctive, variant, of, carcinomas, in, several, anatomic, sites, and, are, distinguished, by, a, marked, tendency, to, lymphovascular, 'invasion,', justifying, the, association, with, 'high-stage', disease, and, poor, prognosis])]). relacion([sujeto(['Several', immunological, mechanisms, underpinning, the, hygiene, hypothesis]), verbo([have]), complemento([been, proposed, such, as, a, shift, in, 'T', helper, cell, 'balance,', 'T', regulatory, cell, 'activity,', or, immune, regulatory, mechanisms, induced, by, the, innate, immunity])]). relacion([sujeto(['To', investigate, whether, the, proposed, immunological, mechanisms, for, the, hygiene, hypotheses, are]), verbo([found]), complemento([in, 'farmers\'', children])]). relacion([sujeto(['We', assessed, gene, expression, levels, of, 64, essential, markers, of, the, innate, and, adaptive, immunity, by, quantitative, 'real-time', 'PCR', in, white, blood, cells, in, 316, 'Swiss', children, of, the, 'PARSIFAL', study, to, compare, 'farmers\'', to, 'non-farmers\'', expressions, and, to]), verbo([associate]), complemento([them, to, the, prevalence, of, asthma, and, 'rhinoconjunctivitis,', total, and, 'allergen-specific', 'IgE', in, 'serum,', and, expression, of, 'Cε', 'germ-line', transcripts])]). relacion([sujeto(['We']), verbo([found]), complemento([enhanced, expression, of, genes, of, the, innate, immunity, such, as, 'IRAK-4', and, 'RIPK1', and, enhanced, expression, of, regulatory, molecules, such, as, 'IL-10,', 'TGF-β,', 'SOCS4,', and, 'IRAK-2', in, 'farmers\'', children])]). relacion([sujeto(['Furthermore,', 'farmers\'', children]), verbo([expressed]), complemento([less, of, the, 'TH1', associated, cytokine, 'IFN-γ', while, 'TH2', associated, transcription, factor, 'GATA3', was, enhanced])]). relacion([sujeto(['Farmers\'', children]), verbo([express]), complemento([multiple, increased, innate, immune, response, and, immune, regulatory, 'molecules,', which, may, contribute, to, the, mechanisms, of, action, of, the, hygiene, hypothesis])]). relacion([sujeto(['Perturbations', in, expression, of, these, proteins, may, disrupt, cell, identity, and]), verbo([trigger]), complemento([tumor, initiation])]). relacion([sujeto(['The', pattern, of, expression, of, a, panel, of, genes]), verbo([involved]), complemento([in, control, of, cell, identity, and, mammary, gland, remodeling, was, investigated, in, two, precancerous, 'lesions,', atypical, ductal, hyperplasia, '(', 'ADH)', and, ductal, carcinoma, in, situ, '(', 'DCIS)', and, compared, to, the, corresponding, histologically, normal, tissue])]). relacion([sujeto(['ADH', and, 'DCIS', showed, a, close, association, in, overexpression, of, 'Polycomb', complex, 'components,', silencing, of, 'Homeobox', 'A', '(', 'HOXA)', cluster, 'gene,', and, overexpression, of, the, genes]), verbo([involved]), complemento([in, estrogen, 'signaling,', 'specifically,', forkhead, box, 'A1', '(', 'FOXA1)', and, 'GATA', binding, protein, 3, '(', 'GATA3)', pioneer, 'factors,', and, estrogen, 'receptor-1', '(', 'ESR1)'])]). relacion([sujeto(['Our', findings, support, the, hypothesis, that, disruption, of, epigenetic, control, is]), verbo([associated]), complemento([with, loss, of, cell, identity, and, acquisition, of, a, constitutive, 'estrogen-dependent', 'terminally-differentiated', luminal, phenotype])]). relacion([sujeto(['Uromodulin', is, a, kidney, specific, glycoprotein, whose, expression, can]), verbo([modulate]), complemento([kidney, homeostasis])]). relacion([sujeto(['However,', the, set, of, sequence, specific, transcription, factors, that]), verbo([regulate]), complemento([the, uromodulin, gene, 'UMOD', and, their, upstream, binding, locations, are, not, well, characterized])]). relacion([sujeto(['We', applied, in, silico, phylogenetic, footprinting, on, the, upstream, regulatory, regions, of, a, diverse, set, of, human, 'UMOD', orthologs, to, identify]), verbo([conserved]), complemento([binding, motifs, and, corresponding, position, specific, weight, matrices])]). relacion([sujeto(['We', further, analyzed, the, predicted]), verbo([binding]), complemento([motifs, by, motif, 'comparison,', which, identified, transcription, factors, likely, to, bind, these, discovered, motifs])]). relacion([sujeto(['Analysis', allowed, the, identification, of, a, reliable, set, of]), verbo([binding]), complemento([motifs, 'in the', upstream, regulatory, regions, of, 'UMOD', to, build, a, high, confidence, compendium, of, transcription, factors, that, could, bind, these, 'motifs,', such, as, 'GATA3,', 'HNF1B,', 'SP1,', 'SMAD3,', 'RUNX2', and, 'KLF4'])]). relacion([sujeto(['ENCODE', deoxyribonuclease, 'I', hypersensitivity, sites, in, the, 'UMOD', upstream, region, of, the, mouse, kidney, confirmed, that, some, of, these]), verbo([binding]), complemento([motifs, were, open, to, binding, by, predicted, transcription, factors])]). relacion([sujeto(['Expression', levels, of, these, transcription, factors, in, the, kidney]), verbo([suggest]), complemento([their, central, role, in, controlling, 'UMOD', expression])]). relacion([sujeto(['GATA']), verbo([binding]), complemento([protein, 3, is, a, zinc, finger, transcription, factor, with, high, affinity, for, urothelial, tissue, and, is, a, promising, immunohistochemical, marker, in, detection, of, urothelial, carcinomas, '(', 'UC)'])]). relacion([sujeto(['Twenty-three', of, 25, cases, of, metastatic, 'UC']), verbo([expressed]), complemento(['GATA3', '(', 92, '%', ')', ;, positive, staining, for, cytokeratin, 7, was, present, in, 23, of, 25, cases, '(', 92, '%', ')', ',', 20, of, 25, '(', 80, '%', ')', stained, for, 'thrombomodulin,', and, 13, of, 25, '(', 52, '%', ')', stained, for, cytokeratin, 20])]). relacion([sujeto(['No', case]), verbo([expressed]), complemento([uroplakin])]). relacion([sujeto(['GATA3']), verbo([has]), complemento([high, sensitivity, and, specificity, for, detection, of, metastatic, 'UC', and, thus, may, play, an, important, role, in, diagnosing, metastatic, 'UC', in, 'CB', samples])]). relacion([sujeto(['Th1', and, 'Th2', cell, fates, are, traditionally, viewed, as, mutually, 'exclusive,', but, recent, work]), verbo([suggests]), complemento([that, these, lineages, may, be, more, plastic, than, previously, thought])]). relacion([sujeto(['DNA', methylation, at, this, region, correlated, with]), verbo([decreased]), complemento(['Gata3', 'levels,', suggesting, a, possible, role, in, controlling, 'Gata3', expression])]). relacion([sujeto(['These', data]), verbo([provide]), complemento([important, insight, into, the, molecular, mechanisms, behind, the, 'co-existence', of, 'Th1', and, 'Th2', characteristics])]). relacion([sujeto(['Both', 'gain-of-function', and, 'loss-of-function', assays, demonstrated, that, 'miR-183', positively]), verbo([regulated]), complemento([3, 'T3-L1', differentiation, by, enhancing, the, expression, of, adipogenic, marker, genes, such, as, 'CCAAT/enhancer', binding, protein, α, '(', 'C/EBPα),', peroxisome, 'proliferator-activated', receptor, γ, '(', 'PPARγ),', adiponectin, and, fatty, acid, synthase, '(', 'FAS),', as, well, as, the, triglyceride, content, and, accumulation, of, lipid, droplets])]). relacion([sujeto(['Meanwhile,', 'low-density', lipoprotein, 'receptor-related', protein, 6, '(', 'LRP6)', was, known, to, impair, the, canonical, 'Wnt/β-catenin', signaling, pathway, and, thereafter, reduce, 'c-myc', and]), verbo([nuclear]), complemento(['β-catenin', protein])]). relacion([sujeto(['We', showed, that, the, inhibition, of, 'LRP6', by, siRNA]), verbo([promoted]), complemento([3, 'T3-L1', adipogenic, differentiation, and, adipogenesis])]). relacion([sujeto(['The', core, promoter, of, 'miR-183', gene, was, identified, and, transcription, factor, 'GATA3', '(', 'GATA']), verbo([binding]), complemento([protein, 3, ')', significantly, inhibited, the, expression, of, mature, 'miR-183', by, binding, to, its, core, promoter, in, 'vivo,', as, indicated, by, the, chromatin, immunoprecipitation, '(', 'ChIP)', assay])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, 'miR-183,', though, negatively, regulated, by, transcription, factor, 'GATA3,', enhances, 3, 'T3-L1', preadipocyte, differentiation, and, adipogenesis, through, the, inhibition, of, the, canonical, 'Wnt/β-catenin', signaling, pathway, by, targeting, 'LRP6'])]). relacion([sujeto(['On', the, other, 'hand,', the, clinical, role, of, progesterone, receptor, '(', 'PgR)', in, 'ER-positive', breast, cancer, remains, 'controversial,', although, testing, of, 'PgR', by, immunohistochemistry, '(', 'IHC)']), verbo([has]), complemento([become, routine])]). relacion([sujeto(['High', expression, of, 'FOXA1', and, 'GATA3', was, significantly]), verbo([associated]), complemento([with, improved, 'disease-free', survival, in, premenopausal, 'women,', but, not, in, postmenopausal, 'women,', whereas, high, expression, of, 'PgR', and, low, expression, of, p53, were, significantly, correlated, with, the, improved, 'disease-free', survival, in, postmenopausal, 'women,', but, not, in, premenopausal, women])]). relacion([sujeto(['Expression', levels, of, 'ER,', 'TFF1,', and, 'RANKL', were, not]), verbo([associated]), complemento([with, the, 'disease-free', survival, in, either, 'pre-', or, postmenopausal, women])]). relacion([sujeto(['Our', results]), verbo([suggest]), complemento([that, the, mechanisms, of, development, and, 'estrogen-dependent', growth, of, 'ER-positive', breast, cancer, might, differ, according, to, menopausal, status])]). relacion([sujeto(['Transcriptional', inactivation, and, 'CpG', island, '(', 'CGI)', methylation, of, 'GATA', transcription, factor, family, members, 'GATA3', and, 'GATA5']), verbo([have]), complemento([been, reported, for, a, few, types, of, human, cancer])]). relacion([sujeto(['Whether', 'high-density', 'CGI', methylation, of, 'GATA3', or, 'GATA5', is]), verbo([associated]), complemento([with, the, clinical, course, of, patients, with, renal, cell, cancer, '(', 'RCC)', has, not, been, clarified])]). relacion([sujeto(['GATA3', and, 'GATA5', 'CGI', relative, methylation, levels, were]), verbo([found]), complemento([to, be, strongly, associated, with, the, state, of, metastasis, '(', 'P=0'])]). relacion([sujeto(['Moreover,', an, independent]), verbo([decrease]), complemento([in, 'RFS', in, 'Cox', proportional, hazard, analysis, was, found, for, tumors, exhibiting, high, 'GATA5', methylation, '(', 'P<0'])]). relacion([sujeto(['Epigenetic', alterations, in, 'GATA', family, members, may, be]), verbo([associated]), complemento([with, aggressive, tumor, phenotypes, in, 'RCC,', and, in, the, case, of, 'GATA5,', may, serve, as, a, new, independent, molecular, marker, for, aggressiveness, and, disease, progression])]). relacion([sujeto(['Suppressors', of, cytokine, signaling, '(', 'SOCS)', family, 'members,', particularly, 'SOCS1', and, 'SOCS3,']), verbo([have]), complemento([been, demonstrated, to, be, important, in, the, regulation, of, 'T', cell, differentiation])]). relacion([sujeto(['Previous', studies, by, our, group, showed, that, the]), verbo([expressed]), complemento([and, purified, fusion, protein, of, cytoplasmic, transduction, peptide, '(', 'CTP)', and, 'HBV', core, antigen, 18, &, #, 8209, ;, 27, '(', 'HBcAg18‑27)‑tapasin', was, able, to, enter, the, cytoplasm, of, bone, 'marrow‑derived', dendritic, cells, '(', 'BMDCs),', promoting, the, maturation, of, 'BMDCs', and, efficiently, enhancing, 'T', cell, immune, responses, in, vitro])]). relacion([sujeto(['In', the, present, 'study,', 'HBcAg‑specific', immune, responses]), verbo([induced]), complemento([by, 'CTP‑HBcAg18‑27‑tapasin', in, 'HBV', were, assessed, in, transgenic, 'mice,', and, 'SOCS1', and, 'SOCS3', were, identified, as, negative, regulators, of, this, response])]). relacion([sujeto(['The', results, demonstrated, that, 'CTP‑HBcAg18‑27‑tapasin', significantly]), verbo([increased]), complemento([the, 'Th1/Th2', cytokine, ratio, in, 'HBV', transgenic, mice])]). relacion([sujeto(['CTP‑HBcAg18‑27‑tapasin', immunization, more, efficiently]), verbo([suppressed]), complemento([the, expression, of, serum, hepatitis, 'B', surface, antigen, '(', 'HBsAg),', 'HBV', 'DNA', as, well, as, liver, 'HBsAg', and, 'HBcAg', in, 'HBV', transgenic, mice])]). relacion([sujeto(['Furthermore,', 'CTP‑HBcAg18‑27‑tapasin']), verbo([promotes]), complemento(['T‑bet', but, reduces, 'GATA‑3', expression])]). relacion([sujeto(['In', 'conclusion,', the, present, study, demonstrated, that, 'CTP‑HBcAg18‑27‑tapasin']), verbo([enhanced]), complemento([the, 'Th1/Th2', cytokine, ratio, and, antiviral, immunity, by, suppressing, 'SOCS1/3', in, 'HBV', transgenic, mice])]). relacion([sujeto(['This', study, evaluates, the, effect, on, the, 'colon\'s', innate, and, adaptive, immune, responses, to, moderate, irradiation, doses, and, the, therapeutic, possibilities, of]), verbo([maintaining]), complemento([immune, homeostasis])]). relacion([sujeto(['LPS', normalized, the, 'CD4⁺', population, and]), verbo([enhanced]), complemento([the, 'CD8⁺', 'population,', whereas, flagellin, maintained, the, 'radiation-induced', elevation, in, the, frequencies, of, both])]). relacion([sujeto(['LPS', and, flagellin, were, strong, inducers, of, 'Th1', cytokines, '(', 'IL-12p35,', 'IL-12p40,', and, 'IFN-γ)', and, 'thus,', contributed, to, a, shift, from, the, 'Th2', polarization]), verbo([induced]), complemento([by, irradiation, toward, a, 'Th1', 'polarization,', confirmed, by, an, increase, of, the, 'T-bet:GATA3', 'ratio,', which, assesses, the, 'Th1', or, 'Th2', status, in, mixed, cell, populations])]). relacion([sujeto(['LPS', and, flagellin, treatment, resulted, in, overexpression, of, 'FoxP3,', 'IL-2Rα', '(', 'CD25),', 'IL-2,', and, 'OX40,', all]), verbo([expressed]), complemento([specifically, and, involved, in, high, levels, of, 'Treg', cell, expansion])]). relacion([sujeto(['These', data]), verbo([suggest]), complemento([that, the, use, of, 'TLR', ligands, limits, the, effects, of, irradiation, on, innate, and, adaptive, immunity])]). relacion([sujeto(['Barakat', syndrome, '(', also, known, as, 'HDR', 'syndrome)', is, an, autosomal, dominant, disorder, characterized, by, 'hypoparathyroidism,', sensorineural, 'deafness,', and, renal, disease]), verbo([caused]), complemento([by, mutation, of, the, 'GATA3', gene, located, at, chromosome, 10, p15])]). relacion([sujeto(['The', exact, prevalence, of, this, disorder, is, not, known, but, is, very, 'rare,', with, only, about, a, dozen, cases]), verbo([reported]), complemento([in, the, literature])]). relacion([sujeto(['Here,', we]), verbo([report]), complemento([a, case, of, 58, -, 'year-old', man, from, 'Ardabil', who, presented, with, seizure, due, to, hypocalcemia])]). relacion([sujeto(['Audiogram', confirmed, sensorineural, hearing]), verbo([loss]), complemento([of, both, sides])]). relacion([sujeto(['He', was, diagnosed, to]), verbo([have]), complemento(['Barakat', syndrome, based, on, his, clinical, and, laboratory, data])]). relacion([sujeto(['Innate', lymphoid, cells, '(', 'ILCs)', specialize, in, the, rapid, secretion, of, polarized, sets, of, cytokines, and, chemokines, to, combat, infection, and]), verbo([promote]), complemento([tissue, repair, at, mucosal, barriers])]). relacion([sujeto(['Their', diversity, and, similarities, with, previously, characterized, natural, killer, '(', 'NK)', cells, and, lymphoid, tissue, inducers, '(', 'LTi)']), verbo([have]), complemento([prompted, a, provisional, classification, of, all, innate, lymphocytes, into, groups, 1, ',', 2, and, 3, solely, on, the, basis, of, cytokine, 'properties,', but, their, developmental, pathways, and, lineage, relationships, remain, elusive])]). relacion([sujeto(['Here', we, identify, and, characterize, a, novel, subset, of, lymphoid, precursors, in, mouse, fetal, liver, and, adult, bone, marrow, that, transiently]), verbo([express]), complemento([high, amounts, of, 'PLZF,', a, transcription, factor, previously, associated, with, 'NK', 'T', cell, 'development,', by, using, lineage, tracing, and, transfer, studies])]). relacion([sujeto(['PLZF(high)', precursors, also]), verbo([expressed]), complemento([high, amounts, of, 'ID2', and, 'GATA3,', as, well, as, 'TOX,', a, known, regulator, of, 'PLZF-independent', 'NK', and, 'LTi', lineages])]). relacion([sujeto(['They', also]), verbo([reveal]), complemento([the, 'broad,', defining, role, of, 'PLZF', in, the, differentiation, of, innate, lymphocytes])]). relacion([sujeto(['Bavachinin,', which, can, be, isolated, from, the, 'Chinese', herb, 'Fructus', 'Psoraleae,']), verbo([has]), complemento([the, potential, as, a, potent, 'anti-asthma', drug])]). relacion([sujeto(['The', results, showed, that, they]), verbo([have]), complemento([different, effects])]). relacion([sujeto(['Bavachinin', and, compound, 'B']), verbo([inhibited]), complemento([green, fluorescent, protein, '(', 'GFP)', production, from, the, 'T', cells, of, 'IL-4-GFP-enhanced', transcript, '(', 4, 'GET)', 'mice,', whereas, compound, 'A', did, not])]). relacion([sujeto(['Bavachinin', and, compound, 'B', can]), verbo([inhibit]), complemento([the, production, of, 'GATA-3', 'mRNA,', but, they, showed, different, effects, on, the, production, of, 'T-bet', mRNA])]). relacion([sujeto(['Compound', 'B']), verbo([increased]), complemento([the, production, of, 'T-bet', 'mRNA,', whereas, 'Bavachinin', did, not])]). relacion([sujeto(['This']), verbo([finding]), complemento([can, enrich, the, database, of, preliminary, drug, screening, from, their, chemical, structures])]). relacion([sujeto(['GATA']), verbo([binding]), complemento([protein, 3, '(', 'GATA3)', was, recently, proposed, to, function, as, a, tumor, suppressor, gene, in, some, types, of, human, cancer])]). relacion([sujeto(['Immunohistochemistry', analysis, indicated, that, 'GATA3', expression, was, significantly]), verbo([decreased]), complemento([in, 225, of, the, 402, '(', 56, '%', ')', gastric, adenocarcinoma, cases])]). relacion([sujeto(['Kaplan-Meier', survival, curves, revealed, that, reduced, expression, of, 'GATA3', was]), verbo([associated]), complemento([with, poor, prognosis, in, gastric, adenocarcinoma, patients, '(', 'P<0'])]). relacion([sujeto(['Our', data]), verbo([suggest]), complemento([that, 'GATA3', plays, an, important, role, in, tumor, progression, and, that, reduced, 'GATA3', expression, independently, predicts, an, unfavorable, prognosis, in, primary, gastric, adenocarcinoma, patients])]). relacion([sujeto(['High-grade', prostate, adenocarcinoma, can]), verbo([have]), complemento([overlapping, morphologic, features, with, 'high-grade', urothelial, 'carcinoma,', a, critical, distinction, as, treatments, differ, substantially])]). relacion([sujeto(['Pseudopapillary', features]), verbo([have]), complemento([not, previously, been, described, in, 'high-grade', acinar, prostate, adenocarcinoma])]). relacion([sujeto(['All', cases, were, transurethral, 'resections,', with, tumor]), verbo([involving]), complemento([the, prostatic, urethra, in, 5, cases, and, 6, with, bladder, involvement])]). relacion([sujeto(['One', case, had, a, separate, focus, of, 'low-grade', noninvasive, urothelial, carcinoma, present, in, the, bladder, and, a, 'better-differentiated', prostate, adenocarcinoma, '(', 'Gleason', score, 4, +, 3, =, 7, ')']), verbo([involving]), complemento([the, prostate, on, needle, biopsy])]). relacion([sujeto(['Although', 'high-grade', prostate, adenocarcinoma, typically]), verbo([has]), complemento([relatively, uniform, 'cytology,', it, can, have, pleomorphic, giant, cell, features, overlapping, with, urothelial, carcinoma])]). relacion([sujeto(['The', presence, of, pseudopapillary, features, in, 'high-grade', prostate, adenocarcinoma, is, a, newly]), verbo([recognized]), complemento([morphologic, overlap, that, can, lead, to, further, diagnostic, difficulty, in, distinguishing, the, 2, entities])]). relacion([sujeto(['For', 'high-grade', tumors]), verbo([involving]), complemento([the, prostatic, urethra, without, typical, admixed, 'lower-grade', prostate, 'adenocarcinoma,', immunohistochemical, studies, for, bladder, and, prostate, markers, should, be, carried, out])]). relacion([sujeto(['The', possibility, to]), verbo([modulate]), complemento([ex, vivo, human, 'NK', cell, differentiation, towards, specific, phenotypes, will, contribute, to, a, better, understanding, of, 'NK', cell, differentiation, and, facilitate, tailored, production, of, 'NK', cells, for, immunotherapy])]). relacion([sujeto(['In', this, 'study,', we, show, that, addition, of, a, specific, low, dose, of, 'IL-12', to, an, ex, vivo, 'NK', cell, differentiation, system, from, cord, blood, 'CD34(+)', stem, cells, will, result, in, significantly]), verbo([increased]), complemento([proportions, of, cells, with, expression, of, 'CD62L', as, well, as, 'KIRs', and, 'CD16', which, are, preferentially, expressed, on, mature, 'CD56(dim)', peripheral, blood, 'NK', cells])]). relacion([sujeto(['In', 'addition,', the, cells, displayed]), verbo([decreased]), complemento([expression, of, receptors, such, as, 'CCR6', and, 'CXCR3,', which, are, typically, expressed, to, a, lower, extent, by, 'CD56(dim)', than, 'CD56(bright)', peripheral, blood, 'NK', cells])]). relacion([sujeto(['The']), verbo([increased]), complemento([number, of, 'CD62L', and, 'KIR', positive, cells, prevailed, in, a, population, of, 'CD33(+)NKG2A(+)', 'NK', 'cells,', supporting, that, maturation, occurs, via, this, subtype])]). relacion([sujeto(['Among', a, series, of, transcription, factors, tested, we]), verbo([found]), complemento(['Gata3', and, 'TOX', to, be, significantly, 'downregulated,', whereas, 'ID3', was, upregulated, in, the, 'IL-12-modulated', ex, vivo, 'NK', 'cells,', implicating, these, factors, in, the, observed, changes])]). relacion([sujeto(['Importantly,', the, cells, differentiated, in, the, presence, of, 'IL-12', showed]), verbo([enhanced]), complemento([cytokine, production, and, cytolytic, activity, against, 'MHC', class, 'I', negative, and, positive, targets])]). relacion([sujeto(['Moreover,', in, line, with, the]), verbo([enhanced]), complemento(['CD16', 'expression,', these, cells, exhibited, improved, 'antibody-dependent', cellular, cytotoxicity, for, 'B-cell', leukemia, target, cells, in, the, presence, of, the, clinically, applied, antibody, rituximab])]). relacion([sujeto(['Altogether,', these, data]), verbo([provide]), complemento([evidence, that, 'IL-12', directs, human, ex, vivo, 'NK', cell, differentiation, towards, more, mature, 'NK', cells, with, improved, properties, for, potential, cancer, therapies])]). relacion([sujeto(['As', macrophages]), verbo([promote]), complemento([the, growth, and, survival, of, malignant, 'T', cells, and, are, abundant, constituents, of, the, tumor, 'microenvironment,', their, functional, polarization, was, examined, in, 'T-cell', lymphoproliferative, disorders])]). relacion([sujeto(['Cytokines', that, are, abundant, within, the, tumor, 'microenvironment,', particularly, interleukin, '(', 'IL)-10,', were, observed, to]), verbo([promote]), complemento([alternative, macrophage, polarization])]). relacion([sujeto(['In', conventional, 'T', 'cells,', the, production, of, 'T', helper, '(', 'Th)2-associated', cytokines, and, 'IL-10,', both, of, which]), verbo([promote]), complemento([alternative, macrophage, 'polarization,', is, regulated, by, the, 'T-cell', transcription, factor, 'GATA-binding', protein, 3, '(', 'GATA-3)'])]). relacion([sujeto(['GATA-3', expression, was, observed, in, 45, '%', of, 'PTCLs,', not, otherwise, specified, '(', 'PTCL,', 'NOS)', and, was]), verbo([associated]), complemento([with, distinct, molecular, 'features,', including, the, production, of, 'Th2-associated', cytokines])]). relacion([sujeto(['Collectively,', these, data]), verbo([suggest]), complemento([that, further, understanding, the, cell, of, origin, and, lymphocyte, ontogeny, among, the, 'T-cell', lymphomas, may, improve, our, understanding, of, the, tumor, 'microenvironment\'s', pathogenic, role, in, these, aggressive, lymphomas])]). relacion([sujeto(['GATA3', mutations, were]), verbo([found]), complemento([to, be, significantly, associated, with, 'luminal-like', breast, cancer, '(', 'P='])]). relacion([sujeto(['GATA3', mutations, mainly, occur, in, patients, with, 'luminal-like', breast, cancer, and]), verbo([have]), complemento([identifiable, clinicopathologic, and, genetic, 'characteristics,', highlighting, a, subgroup, of, patients, with, breast, cancer, in, whom, limited, therapy, may, be, appropriate])]). relacion([sujeto(['The', posttranscriptional, mechanisms, by, which, 'RNA']), verbo([binding]), complemento([proteins, '(', 'RBPs)', regulate, 'T-cell', differentiation, and, cytokine, production, in, vivo, remain, unclear])]). relacion([sujeto(['The', 'RBP', 'HuR']), verbo([binds]), complemento([to, labile, 'mRNAs,', usually, leading, to, increases, in, mRNA, stability, 'and/or', translation])]). relacion([sujeto(['Previous', work, demonstrated, that, 'HuR']), verbo([binds]), complemento([to, the, mRNAs, encoding, the, 'Th2', transcription, factor, 'trans-acting', 'T-cell-specific', transcription, factor, '(', 'GATA-3)', and, 'Th2', cytokines, interleukin, '(', 'IL)-4', and, 'IL-13,', thereby, regulating, their, expression])]). relacion([sujeto(['By', using, a, novel, conditional, 'HuR', knockout, '(', 'KO)', mouse, in, which, 'HuR', is, deleted, in]), verbo([activated]), complemento(['T', 'cells,', we, show, that, 'Th2-polarized', cells, from, heterozygous, 'HuR', conditional, '(', 'OX40-Cre', 'HuR(fl/+))', 'KO', mice, had, decreased, 'steady-state', levels, of, 'Gata3,', 'Il4', and, 'Il13', mRNAs, with, little, changes, at, the, protein, level])]). relacion([sujeto(['Surprisingly,', 'Th2-polarized', cells, from, homozygous, 'HuR', conditional, '(', 'OX40-Cre', 'HuR(fl/fl))', 'KO', mice, showed]), verbo([increased]), complemento(['Il2,', 'Il4', and, 'Il13', mRNA, and, protein, via, different, mechanisms])]). relacion([sujeto(['These', results]), verbo([reveal]), complemento([a, complex, differential, posttranscriptional, regulation, of, cytokines, by, 'HuR', in, which, gene, dosage, plays, an, important, role])]). relacion([sujeto(['These', findings, may]), verbo([have]), complemento([significant, implications, in, allergies, and, 'asthma,', as, well, as, autoimmune, diseases, and, infection])]). relacion([sujeto(['Destructive', periodontitis, is]), verbo([associated]), complemento([with, a, 'Th1-Th17', immune, response, and, activation, of, 'RANKL-induced', osteoclasts])]). relacion([sujeto(['In', 'addition,', 'Porphyromonas', gingivalis, 'K1', and, 'K2', serotypes]), verbo([induce]), complemento([a, strong, 'Th1-Th17', response])]). relacion([sujeto([gingivalis, serotypes]), verbo([induce]), complemento([higher, osteoclasts, 'activation,', by, increased, 'Th17-associated', 'RANKL', 'production,', and, an, 'antigen-specific', memory, 'T-lymphocyte', response])]). relacion([sujeto(['The', 'RANKL', production, and, 'TRAP(+)', osteoclast, induction, were, quantified, on, naïve, 'T', lymphocytes]), verbo([stimulated]), complemento([with, dendritic, cells, primed, with, the, 'P'])]). relacion([sujeto(['T', lymphocytes]), verbo([stimulated]), complemento([by, 'K1', or, 'K2-primed', dendritic, cells, elicited, higher, levels, of, 'RANKL', and, 'TRAP(+)', osteoclasts, than, cells, stimulated, with, the, other, serotypes])]). relacion([sujeto(['Whereas', periodontitis, patients, had, a, higher, frequency, of, memory, 'T', lymphocytes]), verbo([responding]), complemento([to, 'K1', or, 'K2,', healthy, subjects, had, a, higher, frequency, of, memory, 'T', lymphocytes, responding, to, 'K4', or, 'K(-)'])]). relacion([sujeto([gingivalis, serotypes, 'K1', and, 'K2,', but, not, 'others,', are]), verbo([associated]), complemento([with, an, increased, production, of, the, 'osteoclastogenesis-related', factor, 'RANKL'])]). relacion([sujeto(['This', important, information]), verbo([suggests]), complemento([that, these, serotypes, could, elicit, a, greater, bone, resorption, in, vivo, and, have, a, role, in, the, periodontitis, pathogenesis])]). relacion([sujeto(['Vitamin', 'D']), verbo([suppresses]), complemento([inflammation, and, vitamin, 'D', deficiency, is, linked, to, the, severity, of, asthma, symptoms])]). relacion([sujeto(['Peripheral', blood, mononuclear, cells, '(', 'PBMCs)', from, patients, with, radioallergosorbent, test, results, for, house, dust, mite, were]), verbo([stimulated]), complemento([with, allergen, in, the, presence, or, absence, of, vitamin, 'D'])]). relacion([sujeto(['Vitamin', 'D']), verbo([decreased]), complemento([interleukin, '(', 'IL)-9,', 'IL-5,', and, 'IL-8', but, increased, 'IL-13(+)', cells, in, 'TH9', cultures])]). relacion([sujeto(['When', 'PBMCs', from, patients, with, positive, radioallergosorbent, test, results, were]), verbo([stimulated]), complemento([with, dust, mite, 'allergen,', vitamin, 'D', decreased, 'IL-9,', 'IL-5,', and, 'IL-13', in, 'T-helper', cells, '(', 'CD4(+))'])]). relacion([sujeto(['Vitamin', 'D']), verbo([decreased]), complemento([inflammatory, cytokine, profiles, in, 'TH9', memory, cells, and, 'CD4(+)', cells, stimulated, with, dust, mite, allergen])]). relacion([sujeto(['Vitamin', 'D', is, additive, with, dexamethasone, in]), verbo([decreasing]), complemento([inflammatory, cytokine, production, from, 'T-cell', subsets, implicated, in, asthma])]). relacion([sujeto(['This', shows, that, 'allergen-specific', in, vitro, 'Th2', responses, precede, the, detection, of, 'allergen-specific', 'IgE,', which, can]), verbo([provide]), complemento([a, window, of, opportunity, for, novel, therapeutic, interventions])]). relacion([sujeto(['T', helper, '(', 'Th)2', cells]), verbo([have]), complemento([been, proposed, to, play, a, neuroprotective, role, in, multiple, sclerosis, '(', 'MS)'])]). relacion([sujeto(['We', tested, whether, an]), verbo([increase]), complemento([of, 'Th2', responses, '(', &, 'quot;gain-of-function"', 'approach)', could, alter, 'EAE,', the, approach, of, novel, 'GATA', binding, protein, 3, '(', 'GATA3)-transgenic', '(', 'tg)', mice, that, overexpress, 'GATA3,', a, transcription, factor, required, for, 'Th2', differentiation])]). relacion([sujeto(['In', 'EAE']), verbo([induced]), complemento([with, myelin, oligodendrocyte, glycoprotein, '(', 'MOG)35-55', 'peptide,', 'GATA3-tg', mice, had, a, significantly, delayed, onset, of, disease, and, a, less, severe, maximum, clinical, 'score,', compared, with, 'wild-type', 'C57BL/6', mice])]). relacion([sujeto(['Histologically,', 'GATA3-tg', mice, had]), verbo([decreased]), complemento([levels, of, meningitis, and, demyelination, in, the, spinal, 'cord,', and, 'anti-inflammatory', cytokine, profiles, 'immunologically,', however, both, groups, developed, similar, levels, of, 'MOG-specific', lymphoproliferative, responses])]). relacion([sujeto(['During', the, late, 'stage,', only, mitogen, stimulation]), verbo([induced]), complemento([higher, 'IL-4', and, lower, 'interferon-γ', and, 'IL-17', production, in, 'GATA3-tg', mice])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, a, preexisting, bias, toward, a, 'Th2', immune, response, may, reduce, the, severity, of, inflammatory, demyelinating, 'diseases,', including, 'MS'])]). relacion([sujeto(['Interleukin', '(', 'IL)-17A', contributes, to, the, development, of, 'asthma,', especially, in, severe, asthma, which]), verbo([has]), complemento([characteristic, neutrophil, infiltration, in, airways])]). relacion([sujeto(['IL-17A', recombinant, protein, fused, mycobacterial, immunodominant, antigen, 'Ag85A', was, 'constructed,']), verbo([expressed]), complemento([and, purified])]). relacion([sujeto(['We']), verbo([found]), complemento([that, administration, of, mycobacterial, 'Ag85A', and, 'IL-17A', fusion, protein, induced, 'IL-17A', specific, immunoglobulin, '(', 'Ig)G', in, sera, and, significantly, decreased, 'IL-17A', and, 'IL-6', levels, in, bronchoalveolar, lavage, fluid, '(', 'BALF)'])]). relacion([sujeto(['Ag85A-IL-17A', vaccinated, mice, also, showed, marked, reduction, in, the, infiltration, of, inflammatory, cells, in, peribronchiolar, region, and, significant]), verbo([decrease]), complemento([in, total, 'cells,', eosinophil, cells, and, neutrophil, cells, in, 'BALF'])]). relacion([sujeto(['The']), verbo([increased]), complemento([levels, of, 'IL-13', and, 'IL-4', in, 'BALF', of, 'ovalbumin-sensitized', mice, were, significantly, reduced, by, the, administration, of, 'Ag85A-IL-17A'])]). relacion([sujeto(['Furthermore,', 'CD3+CD4+IL-13+', splenocytes]), verbo([stimulated]), complemento([with, 'OVA', and, 'CXCL1', 'mRNA,', 'CCL2', mRNA, and, 'GATA-3', mRNA, expressed, in, lung, tissues, were, decreased, markedly, in, 'Ag85A-IL-17A', vaccinated, group])]). relacion([sujeto(['Our', results, demonstrate, remarkable, antiallergic, effects, of, 'Ag85A-IL-17A', in, a, murine, model, of, asthma, and, it, may]), verbo([have]), complemento([protective, effects, on, allergic, asthma])]). relacion([sujeto(['The', transcription, factor, 'GATA3', is, known, as, a, breast, tumor, suppressor, as, well, as, a, urothelial, 'marker,', and, its]), verbo([loss]), complemento([is, often, seen, in, 'high-grade', invasive, bladder, cancer])]). relacion([sujeto(['Knockdown', of, 'GATA3', in, the, bladder, cancer, lines, '(', 5637, ',', 'TCC-SUP,', 'J82)', resulted, in, promotion, of, cell, migration, and, invasion, as, well, as]), verbo([increases]), complemento([in, the, expression, of, their, related, 'molecules,', such, as, vascular, endothelial, growth, 'factor,', matrix, metalloproteinase, '(', 'MMP)-2,', and, 'MMP-9,', and, the, activity, of, 'MMP-2', and, 'MMP-9'])]). relacion([sujeto(['GATA3']), verbo([loss]), complemento([was, also, associated, with, an, increasing, level, of, a, mesenchymal, marker, 'N-cadherin', and, a, decreasing, level, of, an, epithelial, marker, 'β-catenin'])]). relacion([sujeto(['Consistent', with, these, 'findings,', enforced, expression, of, 'GATA3', in, 'UMUC3']), verbo([inhibited]), complemento([cell, migration, and, invasion])]). relacion([sujeto(['These', findings]), verbo([suggest]), complemento([that, 'GATA3', plays, an, important, role, in, the, prevention, of, bladder, cancer, progression, and, metastasis, by, inhibiting, cell, migration, and, invasion, as, well, as, 'epithelial-to-mesenchymal', transition])]). relacion([sujeto(['We', present, the, case, of, a, 'Dutch', family, with, a, new, mutation, '(', 'c523_528dup)', in, 'GATA3']), verbo([causing]), complemento(['HDR', syndrome])]). relacion([sujeto(['Although', 2, patients, displayed, vestibular, 'symptoms,', no, anomalies, in, the, vestibular, system, were]), verbo([found]), complemento([by, 'vestibulo-ocular', examination])]). relacion([sujeto(['CAKUT', can, be]), verbo([caused]), complemento([by, monogenic, 'mutations;', 'however,', data, are, lacking, on, their, frequency])]). relacion([sujeto(['Genetic', diagnosis]), verbo([has]), complemento([been, hampered, by, genetic, heterogeneity, and, lack, of, 'genotype-phenotype', correlation])]). relacion([sujeto(['Furthermore,', several, mutations, previously]), verbo([reported]), complemento([to, be, 'disease-causing', are, most, likely, benign, variants])]). relacion([sujeto(['Thus,', in, a, large, cohort, over, 6, '%', of, families, with, isolated, 'CAKUT', are]), verbo([caused]), complemento([by, a, mutation, in, 12, of, 17, dominant, 'CAKUT', genes])]). relacion([sujeto(['Our']), verbo([report]), complemento([represents, one, of, the, most, 'in-depth', diagnostic, studies, of, monogenic, causes, of, isolated, 'CAKUT', in, children])]). relacion([sujeto(['Except', after, neck, 'surgery,', hypoparathyroidism, is, a, rare, disease]), verbo([caused]), complemento([by, defects, in, genes, involved, in, parathyroid, gland, development, '(', 'TBX1/22q11'])]). relacion([sujeto(['Recurrent', missense, mutations, in, 'AP2S1,', a, 'calcium-sensing', receptor, 'regulator,']), verbo([have]), complemento([been, recently, identified, in, familial, hyperparathyroidism])]). relacion([sujeto(['None', of, the, 60, patients, presented, with, nucleotidic, changes, or, copy, number, variation, in, the, 'AP2S1', 'gene,', thereby, excluding, 'AP2S1', defects, as, a, frequent]), verbo([cause]), complemento([of, isolated, hypoparathyroidism])]). relacion([sujeto(['Positive']), verbo([nuclear]), complemento([staining, for, 'GATA3', was, found, to, be, present, in, 90, '%', of, metastatic, breast, carcinoma, specimens, '(', 27, of, 30, 'specimens)'])]). relacion([sujeto(['Staining', results, were, unambiguous, because, all, positive, cases, demonstrated, intense]), verbo([nuclear]), complemento([staining, in, &, 'gt;', 50, '%', of, tumor, cells])]). relacion([sujeto(['Mammaglobin', '(', 57, '%', 'staining;', 17, of, 30, 'cases)', and, 'GCDFP-15', '(', 33, '%', 'staining;', 10, of, 30, 'cases)', were]), verbo([found]), complemento([to, be, less, sensitive, markers, of, breast, carcinoma])]). relacion([sujeto(['If', used, in, a, 'panel,', mammaglobin, and, 'GCFP-15', staining, would]), verbo([have]), complemento([identified, only, 1, additional, case, compared, with, those, stained, with, 'GATA3'])]). relacion([sujeto(['Group', 3, innate, lymphoid, cells, '(', 'ILC3)', include, 'IL-22-producing', 'NKp46(+)', cells, and, 'IL-17A/IL-22-producing', 'CD4(+)', lymphoid, tissue, inducerlike, cells, that]), verbo([express]), complemento(['RORγt', and, are, implicated, in, protective, immunity, at, mucosal, surfaces])]). relacion([sujeto(['We']), verbo([found]), complemento([that, abundant, 'GATA-3', protein, is, expressed, in, 'mucosa-associated', 'ILC3', subsets, with, levels, intermediate, between, mature, 'B', cells, and, 'ILC2'])]). relacion([sujeto(['Chimeric', mice, generated, with, 'Gata3-deficient', fetal, liver, hematopoietic, precursors, lack, all, intestinal, 'RORγt(+)', 'ILC3', 'subsets,', and, these, mice, show, defective, production, of, 'IL-22', early, after, infection, with, the, intestinal, pathogen, 'Citrobacter', 'rodentium,']), verbo([leading]), complemento([to, impaired, survival])]). relacion([sujeto(['Further', analyses, demonstrated, that, 'ILC3', development]), verbo([requires]), complemento(['cell-intrinsic', 'Gata3', expression, in, fetal, liver, hematopoietic, precursors])]). relacion([sujeto(['Our', results, demonstrate, that, 'Gata3', plays, a, generalized, role, in, 'ILC', lineage, determination, and, is, critical, for, the, development, of, gut, 'RORγt(+)', 'ILC3', subsets, that]), verbo([maintain]), complemento([mucosal, barrier, homeostasis])]). relacion([sujeto(['High-fat', diets, '(', 'HFD)']), verbo([promote]), complemento([the, development, of, both, obesity, and, fatty, liver, disease, through, the, 'up-regulation', of, hepatic, lipogenesis])]). relacion([sujeto(['Insulin', 'resistance,', a, hallmark, of, both, 'conditions,']), verbo([causes]), complemento([dysfunctional, fuel, partitioning, and, increases, in, lipogenesis])]). relacion([sujeto(['Recent', work]), verbo([has]), complemento([demonstrated, that, systemic, insulin, resistance, occurs, in, as, little, as, the, first, 72, hours, of, an, 'HFD,', suggesting, the, potential, for, hepatic, disruption, with, 'HFD', at, this, time, point])]). relacion([sujeto(['However,', only, the, males, fed, the, 'HFD', had, a, significant]), verbo([increase]), complemento([in, body, fat])]). relacion([sujeto(['Regardless', of, 'sex,', 'HFD']), verbo([caused]), complemento(['down-regulation', of, lipogenic, and, inflammatory, genes])]). relacion([sujeto(['This', may]), verbo([suggest]), complemento([that, females, are, more, responsive, to, the, acute, hepatic, injury, effects, caused, by, 'HFDs'])]). relacion([sujeto(['In', 'addition,', female, rats, appear, to]), verbo([have]), complemento([protection, from, increases, in, fat, 'deposition,', possibly, due, to, increased, caloric, 'expenditure;', male, rats, fed, an, 'HFD', were, less, 'active,', as, demonstrated, by, distance, traveled, in, their, home, cage])]). relacion([sujeto(['Whereas', 'OVA', allergen, exposure, did, not]), verbo([induce]), complemento([inflammation, in, 'WT', 'controls,', 'CD2-Gata3', 'Tg', mice, showed, clear, 'AAI', and, enhanced, levels, of, 'IL-5', and, 'IL-13', in, bronchoalveolar, lavage])]). relacion([sujeto(['Compared', with, 'WT', 'littermates,', 'CD2-Gata3', 'Tg', mice, contained]), verbo([increased]), complemento([numbers, of, 'ILC2,', which, expressed, high, levels, of, 'IL-33R', and, contributed, significantly, to, early, production, of, 'IL-4,', 'IL-5,', and, 'IL-13'])]). relacion([sujeto(['CD2-Gata3', 'Tg', mice, also, had, a, unique, population, of, 'IL-33-responsive', 'non-B/non-T', lymphoid, cells]), verbo([expressing]), complemento(['IFN-γ'])]). relacion([sujeto(['Enforced', 'Gata3', expression, is, therefore, sufficient, to]), verbo([enhance]), complemento(['Th2', and, 'ILC2', 'activity,', and, leads, to, increased, susceptibility, to, 'AAI', after, mild, exposure, to, inhaled, harmless, 'Ags', that, otherwise, induce, 'Ag', tolerance])]). relacion([sujeto([9, ',', 'respectively),', and, inversely, correlated, with]), verbo([nuclear]), complemento([grade, '(', 'P = 0'])]). relacion([sujeto(['Expression', of, 'GATA-3', and, 'FOXA1', was]), verbo([associated]), complemento([with, better, prognosis])]). relacion([sujeto(['GATA-3', and, 'FOXA1', are]), verbo([associated]), complemento([with, a, less, aggressive, phenotype, and, a, better, prognosis, in, patients, with, 'HR-positive/HER2-negative', breast, cancer])]). relacion([sujeto(['FOXA1', may, be, useful, in, identifying, those, patients, who, may, not]), verbo([require]), complemento([adjuvant, 'CT'])]). relacion([sujeto(['The', 'T-cell', immunoglobulin, and, mucin, 'domain-(Tim)-1', molecule, and, 'Tim-3', are, mainly]), verbo([expressed]), complemento([on, activated, 'T', helper, '(', 'Th)', 2, and, 'Th1', 'cells,', 'respectively,', and, have, been, implicated, in, the, pathogenesis, of, some, autoimmune, diseases])]). relacion([sujeto(['Immune', thrombocytopenia, '(', 'ITP)', is, a, common, autoimmune, 'disorder,', and, the, complex, dysregulation, of, cellular, immunity]), verbo([has]), complemento([been, 'observed;', 'however,', the, relationship, between, 'Tims', and, excessive, immune, responses, in, 'ITP', remains, unclear])]). relacion([sujeto(['Using', 'real-time', quantitative, polymerase, chain, reaction, '(', 'RT-PCR),', the, mRNA, expression, levels, of, 'Tim-1,', 'Tim-3,', 'T-box', transcription, factor, '(', 'T-bet)', and, 'GATA']), verbo([binding]), complemento([protein, 3, '(', 'GATA-3)', were, measured, in, the, peripheral, blood, mononuclear, cells, '(', 'PBMCs)', of, 45, newly, diagnosed, patients, with, active, 'ITP,', 34, 'ITP', patients, in, remission, and, 31, healthy, volunteers])]). relacion([sujeto(['At', the, same, 'time,', 'Tim-1', mRNA, was, not, significantly, 'declined,', which, resulted, in, a]), verbo([decreased]), complemento([ratio, of, 'Tim-3', to, 'Tim-1', in, 'ITP', patients, with, active, disease])]). relacion([sujeto(['The', reduced, levels, of, 'Tim-3/Tim-1', in, 'PBMCs', during, active, stages, of, the, disease]), verbo([suggest]), complemento([a, possible, role, in, the, pathogenesis, and, course, of, 'ITP'])]). relacion([sujeto(['Here,', we, evaluate, the, influence, of, human, 'MSCs', derived, from, umbilical, cord, matrix, '(', 'UCM),', bone, marrow, '(', 'BM)', and, adipose, tissue, '(', 'AT),', 'co-cultured', with, phytohemagglutinin, '(', 'PHA)-stimulated', peripheral, blood, mononuclear, cells, '(', 'MNC),', on, 'T,', 'B', and, natural, killer, '(', 'NK)', cell, 'activation;', 'T', and, 'B', 'cells\'', ability, to, acquire, lymphoblast, 'characteristics;', mRNA, expression, of, 'interleukin-2', '(', 'IL-2),', forkhead, box, 'P3', '(', 'FoxP3),', 'T-bet', and, 'GATA']), verbo([binding]), complemento([protein, 3, '(', 'GATA3),', on, purified, 'T', 'cells,', and, tumor, necrosis, 'factor-alpha', '(', 'TNF-α),', perforin, and, granzyme, 'B', on, purified, 'NK', cells])]). relacion([sujeto(['MSCs', derived, from, all, three, tissues, were, able, to]), verbo([prevent]), complemento(['CD4+', and, 'CD8+', 'T', cell, activation, and, acquisition, of, lymphoblast, characteristics, and, 'CD56', dim, 'NK', cell, 'activation,', wherein, 'AT-MSCs', showed, a, stronger, inhibitory, effect])]). relacion([sujeto(['Besides,', when, 'co-cultured', with, 'PHA-stimulated', 'MNC,', 'MSCs', seem, to]), verbo([promote]), complemento(['Treg', and, 'Th1', 'polarization,', estimated, by, the, increased, expression, of, 'FoxP3', and, 'T-bet', mRNA, within, purified, activated, 'T', 'cells,', and, to, reduce, 'TNF-α', and, perforin, production, by, activated, 'NK', cells])]). relacion([sujeto(['Overall,', 'UCM-,', 'BM-', and, 'AT-derived', 'MSCs', hamper, 'T', 'cell,', 'B', cell, and, 'NK', 'cell-mediated', immune, response, by]), verbo([preventing]), complemento([their, acquisition, of, lymphoblast, 'characteristics,', activation, and, changing, the, expression, profile, of, proteins, with, an, important, role, in, immune, 'function,', except, 'UCM-MSCs', showed, no, inhibitory, effect, on, 'B', cells, under, these, experimental, conditions])]). relacion([sujeto(['Here', we, demonstrate, that, the, clinically, 'well-tolerated', 'KDACi', vorinostat, and, givinostat, revert, diabetes, in, the, nonobese, diabetic, '(', 'NOD)', mouse, model, of, type, 1, diabetes, and, counteract, inflammatory]), verbo([target]), complemento([cell, damage, by, a, mechanism, of, action, consistent, with, transcription, 'factor--rather', than, global, 'chromatin--hyperacetylation'])]). relacion([sujeto(['Diabetes', incidence, was, reduced, by, 38, '%', and, 45, '%', ',', 'respectively,', there, was, a, 15, '%']), verbo([increase]), complemento([in, the, percentage, of, islets, without, 'infiltration,', and, pancreatic, insulin, content, increased, by, 200, '%'])]). relacion([sujeto(['Vorinostat', treatment]), verbo([increased]), complemento([the, frequency, of, functional, regulatory, 'T-cell', subsets, and, their, transcription, factors, 'Gata3', and, 'FoxP3', in, parallel, to, a, decrease, in, inflammatory, dendritic, cell, subsets, and, their, cytokines, 'IL-6,', 'IL-12,', and, 'TNF-α'])]). relacion([sujeto(['KDACi', also]), verbo([inhibited]), complemento(['LPS-induced', 'Cox-2', expression, in, peritoneal, macrophages, from, 'C57BL/6', and, 'NOD', mice])]). relacion([sujeto(['Further,', 'NF-κB', genomic, iNos, promoter]), verbo([binding]), complemento([was, reduced, by, 50, '%', ',', and, 'NF-κB-dependent', mRNA, expression, was, blocked])]). relacion([sujeto(['These', effects, were]), verbo([associated]), complemento([with, 'NF-κB', subunit, p65, hyperacetylation])]). relacion([sujeto(['Taken', 'together,', these, data]), verbo([provide]), complemento([a, rationale, for, clinical, trials, of, safety, and, efficacy, of, 'KDACi', in, patients, with, autoimmune, disease, such, as, type, 1, diabetes])]). relacion([sujeto(['The', natural, product, oleanolic, acid, is, commonly]), verbo([found]), complemento([in, a, variety, of, medicinal, plants])]). relacion([sujeto(['The', aim, of, the, current, study, was, to, use, a, mouse, model, of, allergic, asthma, to, investigate, whether, oleanolic, acid]), verbo([has]), complemento(['anti-asthmatic', 'effects,', and, if, 'so,', to, determine, the, mechanism, of, these, effects])]). relacion([sujeto(['Oleanolic', acid]), verbo([suppressed]), complemento([eosinophil, 'infiltration,', allergic, airway, 'inflammation,', and, 'Penh,', which, occurred, by, suppressing, the, production, of, 'IL-5,', 'IL-13,', 'IL-17,', and, 'ovalbumin-specific', 'IgE', through, the, upregulation, of, 'T-bet', and, 'Foxp3,', and, the, downregulation, of, 'GATA-3', and, 'RORγt'])]). relacion([sujeto(['It', is, therefore, reasonable, to]), verbo([suggest]), complemento([that, the, 'anti-inflammatory', and, 'anti-asthmatic', effects, of, oleanolic, acid, may, be, exerted, through, inhibition, of, the, 'GATA-3', and, 'RORγt', pathways])]). relacion([sujeto(['However,', choosing, and, verifying, combinations, of, 'TFs', for, specific, cell, differentiation]), verbo([have]), complemento([been, daunting, due, to, the, large, number, of, possible, combinations, of, '∼2,000', 'TFs'])]). relacion([sujeto(['Here,', we]), verbo([report]), complemento([the, identification, of, individual, 'TFs', for, 'lineage-specific', cell, differentiation, based, on, the, correlation, matrix, of, global, gene, expression, profiles])]). relacion([sujeto(['Furthermore,', transfection, of, synthetic, mRNAs, of, 'TFs', generates, their, appropriate]), verbo([target]), complemento([cells])]). relacion([sujeto(['Moderate', physical, activity]), verbo([has]), complemento([been, shown, to, promote, immunity])]). relacion([sujeto(['Different', moderate, physical, activities, may]), verbo([have]), complemento([different, effects, on, immunity])]). relacion([sujeto(['This', study, investigated, the, impacts, of, a, 12, -, week]), verbo([regular]), complemento([music, aerobic, exercise, '(', 'MAE)', program, on, leukocyte, 'distribution,', lymphocyte, 'subsets,', and, lymphocyte, polarization])]). relacion([sujeto(['Forty-seven', 'middle-age', women, were]), verbo([recruited]), complemento([for, this, study])]). relacion([sujeto(['Results', showed, that, the, 'MAE', exercise, for, 12, weeks, 'didn\'t', change, red, blood, cells, or, total, leukocytes, but]), verbo([increased]), complemento([lymphocyte, counts])]). relacion([sujeto(['The', women, in, 'MAE', group, revealed, significant]), verbo([increases]), complemento(['(', 'P', '≤', 0.01, ')', of, 'CD3CD4,', 'CD3CD8,', and, 'CD4CD25', 'cells,', associated, with, 'Treg', polarization, showing, enhanced, 'FoxP3', but, not, 'T-bet,', 'Gata-3,', or, 'RORγT', expression, '(', 'P', &, 'lt;'])]). relacion([sujeto(['This', study, shows, that, 'MAE']), verbo([increases]), complemento([specific, lymphocyte, subsets, and, enhances, 'Treg', cell, differentiation])]). relacion([sujeto(['It', is]), verbo([suggested]), complemento([to, encourage, moderate, physical, activity, of, music, aerobic, exercise, to, enhance, lymphocyte, function, of, 'middle-aged', women])]). relacion([sujeto(['Compared', with, control, 'group,', three, 'HF', groups, showed, significantly]), verbo([increased]), complemento([levels, of, 'INF-γ', and, 'IL-2', '(', all, 'P', &, 'lt;', 0.05, ')', ',', and, significantly, decreased, concentrations, of, 'IL-4', and, 'IL-10(all', 'P', &, 'lt;', 0.05, ')'])]). relacion([sujeto(['The', expression, of, 'T-bet', mRNA]), verbo([increased]), complemento([and, the, expression, of, 'GATA-3', mRNA, decreased, '(', all, 'P', &, 'lt;', 0.05, ')', in, 'ITP', mice, after, intragastric, administration, with, different, dose, of, 'HF'])]). relacion([sujeto(['HF', significantly, recovered, peripheral, platelet, counts, in, 'ITP', mice, through]), verbo([promoting]), complemento(['Th1', cell, differentiation, and, attenuating, 'Th2', differentiation, in, 'ITP', mice])]). relacion([sujeto(['In', this, 'study,', we, demonstrate, that, 'Bach2', plays, crucial, roles, in]), verbo([maintaining]), complemento(['T', cell, quiescence, and, governing, the, 'differentiation,', 'activation,', and, survival, of, 'Foxp3(+)', regulatory, 'T', '(', 'Treg)', cells])]). relacion([sujeto(['Without', 'Bach2,', 'Treg', cells, exhibit, diminished, 'Foxp3', 'expression,', depleted, 'numbers,', 'hyperactivation,']), verbo([enhanced]), complemento(['proliferation,', and, profound, loss, of, competitive, fitness, in, vivo])]). relacion([sujeto(['Mechanistically,', reduced, survival, of, 'Bach2-deficient', 'Treg', cells, was]), verbo([associated]), complemento([with, reduced, 'Bcl-2', and, 'Mcl-1', levels, and, elevated, 'Bim/Bcl-2', ratio])]). relacion([sujeto(['Additionally,', 'Bach2', deficiency]), verbo([induced]), complemento([selective, loss, of, 'Helios(-)Foxp3(+)', 'Treg', cells, and, a, 'Treg', cell, transcriptome, skewed, toward, the, 'Th1/Th2', effector, program, at, the, expense, of, the, 'Treg', program])]). relacion([sujeto(['Importantly,', perturbations, in, the, differentiation, of]), verbo([induced]), complemento(['Treg', cells, was, linked, to, a, fatal, 'Th2-type', chronic, inflammatory, lung, disease, in, 'Bach2-deficient', mice])]). relacion([sujeto(['Thus,', 'Bach2', enforces, 'T', cell, 'quiescence,']), verbo([promotes]), complemento([the, development, and, survival, of, 'Treg', 'lineage,', restrains, aberrant, differentiation, of, 'Treg', 'cells,', and, protects, against, 'immune-mediated', diseases])]). relacion([sujeto(['Asthma', is, one, of, the, serious, global, health, problems, and]), verbo([cause]), complemento([of, huge, mortality, and, morbidity])]). relacion([sujeto(['It', is, characterized, by, persistent, airway, 'inflammation,', airway, 'hyperresponsiveness,']), verbo([increased]), complemento(['IgE', levels, and, mucus, hypersecretion])]). relacion([sujeto(['Asthma', is]), verbo([mediated]), complemento([by, dominant, 'Th2', immune, 'response,', causing, enhanced, expression, of, 'Th2', cytokines])]). relacion([sujeto(['These', cytokines, are, responsible, for, the, various, pathological, changes]), verbo([associated]), complemento([with, allergic, asthma])]). relacion([sujeto(['The', role, of, 'Th2', cells, in, the, pathogenesis, of, the, asthma, is, primarily]), verbo([mediated]), complemento([through, the, cytokine, 'IL-13,', also, produced, by, type, 2, innate, lymphoid, 'cells,', that, comes, under, the, transcriptional, regulation, of, 'GATA3'])]). relacion([sujeto(['Inhibition', of, 'GATA3', activity, or, blockade, of, 'GATA3', expression, may, attenuate, the, 'interleukin-13']), verbo([mediated]), complemento([asthma, phenotypes])]). relacion([sujeto(['So,', 'GATA3', might, be, a, potential, therapeutic]), verbo([target]), complemento([for, the, treatment, of, allergic, asthma])]). relacion([sujeto(['Follicular', helper, 'T', '(', 'Tfh)', cells, are, dedicated, to]), verbo([providing]), complemento([help, to, 'B', cells, and, are, strongly, associated, with, 'antibody-mediated', autoimmune, disease])]). relacion([sujeto(['Our', data, demonstrate, that, 'CD4(+)CXCR5(+)PD-1(+)', 'Tfh', 'cells,', 'Bcl-6', and, 'IL-21', were, significantly]), verbo([increased]), complemento([in, 'EAMG', 'mice,', compared, with, controls])]). relacion([sujeto(['In', 'addition,', we]), verbo([found]), complemento([that, frequencies, of, 'Tfh', cells, were, positively, correlated, with, the, levels, of, serum, 'anti-AChR', 'Ab'])]). relacion([sujeto(['In-vivo', transduction, of, 'lenti-siRNA-Bcl6', ameliorates, the, severity, of, ongoing, 'EAMG', with]), verbo([decreased]), complemento(['Tfh', 'cells,', 'Bcl-6', and, 'IL-21', 'expression,', and, leads, to, decreased, 'anti-AChR', antibody, levels])]). relacion([sujeto(['Furthermore,', we]), verbo([found]), complemento([that, siRNA, knockdown, of, 'Bcl-6', expression, increases, the, expression, of, 'Th1(IFN-γ,', 'T-bet)', and, 'Th2', markers, '(', 'IL-4', and, 'GATA3),', but, failed, to, alter, the, expression, of, 'Th17-related', markers, '(', 'RORγt,', 'IL-17)', and, 'Treg', markers, '(', 'FoxP3)'])]). relacion([sujeto(['Our', study]), verbo([suggests]), complemento([that, 'Tfh', cells, contribute, to, the, antibody, production, and, could, be, one, of, the, most, important, 'T', cell, subsets, responsible, for, development, and, progression, of, 'EAMG', or, 'MG'])]). relacion([sujeto(['Bcl-6']), verbo([provides]), complemento([a, promising, therapeutic, target, for, immunotherapy, not, only, for, 'MG,', but, also, for, other, 'antibody-mediated', autoimmune, diseases])]). relacion([sujeto(['More', 'recently,', 'GATA3', was, shown, to, be]), verbo([involved]), complemento([in, skin, cell, lineage, 'determination,', in, morphogenesis, and, maintenance, of, hair, follicle, keratinocytes, as, well, as, in, epidermal, barrier, formation, in, mouse])]). relacion([sujeto(['We', showed, that, 'GATA3', inhibition]), verbo([increased]), complemento([cell, 'number,', 'BrdU', incorporation, and, expression, of, the, proliferation, markers, 'PCNA', and, 'Ki67,', demonstrating, that, 'GATA3', can, inhibit, keratinocyte, proliferation])]). relacion([sujeto(['Moreover,', 'GATA3', seems, to, be, able, to]), verbo([induce]), complemento([keratinocyte, differentiation, since, its, silencing, leads, to, a, decrease, of, both, early, and, late, differentiation, markers, such, as, 'Keratins', 1, and, 10, ',', 'Involucrin', and, 'Loricrin'])]). relacion([sujeto(['Our', results, demonstrate, that, 'GATA3', transcription, factor]), verbo([inhibits]), complemento([proliferation, and, induces, differentiation, of, primary, 'keratinocytes,', which, suggest, that, it, may, regulate, human, interfollicular, epidermal, renewal])]). relacion([sujeto(['Epidemiological', data]), verbo([associate]), complemento([protection, from, allergic, diseases, with, the, exposure, to, certain, infectious, agents, during, early, stages, of, life])]). relacion([sujeto(['Modulation', of, the, immune, response, by, pathogens]), verbo([has]), complemento([been, considered, to, be, a, major, factor, influencing, this, protection])]). relacion([sujeto(['Recent', evidence, indicates, that, immunoregulatory, mechanisms]), verbo([induced]), complemento([upon, infection, ameliorate, allergic, disorders])]). relacion([sujeto(['A', longitudinal, study]), verbo([has]), complemento([demonstrated, reduced, frequency, and, incidence, of, asthma, in, children, who, reported, a, prior, infection, with, 'Salmonella'])]). relacion([sujeto(['Experimental', studies]), verbo([involving]), complemento(['Salmonella', enterica, serovar, 'Typhimurium-infected', murine, models, have, confirmed, protection, from, induced, allergic, airway, 'inflammation;', 'however,', the, underlying, cause, leading, to, this, amelioration, remains, incompletely, defined])]). relacion([sujeto(['We', observed, a, significant]), verbo([increase]), complemento([in, 'CD11b+', 'Gr1+', myeloid, cell, populations, in, mice, after, infection, with, 'S'])]). relacion([sujeto(['These', findings, signify, the, contribution, of, myeloid, cells, in]), verbo([preventing]), complemento(['Th2-mediated', diseases, and, suggest, their, possible, application, as, therapeutics])]). relacion([sujeto(['Often', the, distinction, of, cutaneous, apocrine, carcinoma, from, metastatic, mammary, apocrine, carcinoma, to, the, skin, can, be, a, diagnostic, dilemma, because, both, tumors, share, similar, histologic, features, and]), verbo([have]), complemento([overlapping, immunohistochemical, profile])]). relacion([sujeto(['The', rs6737848, 'SOCS5', polymorphism, was, significantly]), verbo([associated]), complemento([with, asthma, in, additive, model, '(', p, =, 0.05, ',', 'OR', =, 0.338, ',', 95, '%', 'CI', 0.158, -, 0.723, ')', and, in, dominant, model, '(', p, =, 0.02, ',', 'OR', =, 0.284, ',', 'CI', 0.126, -, 0.638, ')'])]). relacion([sujeto(['None', of, the, polymorphisms, of, the, studied, genes, was]), verbo([associated]), complemento([with, total, 'IgE', levels])]). relacion([sujeto(['This', is, the, first]), verbo([report]), complemento([on, the, association, of, rs6737848, 'SOCS5', with, asthma])]). relacion([sujeto(['Hence,', there, is, significant, interest, in, understanding, the, mechanisms]), verbo([regulating]), complemento(['ESR1', gene, expression])]). relacion([sujeto(['Proteasome', activity, is]), verbo([increased]), complemento([in, cancer, and, we, previously, showed, that, proteasome, inhibition, leads, to, loss, of, 'ESR1', gene, expression, in, breast, cancer, cells])]). relacion([sujeto(['Here,', we, show, that]), verbo([loss]), complemento([of, 'ESR1', gene, expression, induced, by, the, proteasome, inhibitor, bortezomib, is, associated, with, inactivation, of, a, distal, enhancer, located, 150, kilobases, '(', 'kb)', from, the, 'TSS'])]). relacion([sujeto(['Chromatin', immunoprecipitation, assays]), verbo([reveal]), complemento([several, 'bortezomib-induced', changes, at, the, distal, site, including, decreased, occupancy, of, three, critical, transcription, 'factors,', 'GATA3,', 'FOXA1,', and, 'AP2γ'])]). relacion([sujeto(['Bortezomib', treatment, also, resulted, in]), verbo([decreased]), complemento([histone, 'H3', and, 'H4', acetylation, and, decreased, occupancy, of, histone, 'acetyltransferase,', p300])]). relacion([sujeto(['These', data]), verbo([suggest]), complemento([a, mechanism, to, explain, proteasome, 'inhibitor-induced', loss, of, 'ESR1', mRNA, expression, that, highlights, the, importance, of, the, chromatin, environment, at, the, -, 150, kb, distal, enhancer, in, regulation, of, basal, expression, of, 'ESR1', in, breast, cancer, cells])]). relacion([sujeto(['Gastric', cancer, is, a, major, health, problem, 'worldwide;', it, is, the, second, most, common]), verbo([cause]), complemento([of, cancer, death, in, the, world])]). relacion([sujeto(['Recent', studies, indicate, that, the, 'high-mobility', group, '(', 'HMG)', of, chromosomal, proteins, is]), verbo([associated]), complemento([with, cancer, progression])]). relacion([sujeto(['However,', 'HMGB3']), verbo([has]), complemento([been, little, studied])]). relacion([sujeto(['We', analyzed, the, 'co-expression', network, between, 'HMGB3', and, 'differentially-expressed', genes, in, the, 'GSE17187', 'database,', identifying, the, relevant, transcription, 'factors,', and, the]), verbo([conserved]), complemento([domain, of, 'HMGB3', to, understand, the, underlying, regulation, mechanisms, involved, in, gastric, cancer])]). relacion([sujeto(['Thirty-one', relationships, between, 11, 'differentially-expressed', genes, were, included, in, a, 'co-expression', 'network;', many, of, these, genes]), verbo([have]), complemento([been, identified, as, related, to, 'cancer,', including, 'TBX5', and, 'TFR2'])]). relacion([sujeto(['Further', analysis, identified, nine, transcription, 'factors,', these, being, 'GATA3,', 'MZF1,', 'GATA1,', 'GATA2,', 'SRY,', 'REL,', 'NFYB,', 'NFYC,', and, 'NFYA,', which, could]), verbo([interact]), complemento([with, 'HMGB3', to, regulate, target, gene, expression, and, consequently, regulate, gastric, cancer, cell, 'proliferation,', migration, and, invasion])]). relacion([sujeto(['The', 'HMG-box', domain, was, very, similar, in, various, 'species,', with, only, a, few, amino, acid, 'changes,', indicating]), verbo([conserved]), complemento([functions, in, 'HMG-box'])]). relacion([sujeto(['This', information, helps, to]), verbo([provide]), complemento([insight, into, the, molecular, mechanisms, of, 'HMGB3', in, human, gastric, cancer])]). relacion([sujeto(['Abnormal', cellular, immunity]), verbo([induced]), complemento([by, deranged, 'Th1/Th2', profile, has, been, revealed, to, play, a, critical, role, in, the, pathogenesis, of, immune, thrombocytopenic, purpura, '(', 'ITP)'])]). relacion([sujeto(['T-bet', and, 'GATA-3', are, the, two, transcriptional, factors, that]), verbo([have]), complemento([been, indicated, to, be, the, master, regulators, for, 'Th1', and, 'Th2', lineage, 'commitment,', respectively])]). relacion([sujeto(['In', the, presence, of, 100, 'ng/ml', 'IL-11,', 'GATA-3', transcript, abundance, rose, up, to, '~85-fold', of, that, measured, in, untreated, 'cells,', whereas, 'T-bet', transcripts, were, lowered, merely, to, '~41%,']), verbo([suggesting]), complemento([that, 'GATA-3', was, the, major, contributor, for, the, reversal, of, 'T-bet/GATA-3', ratio])]). relacion([sujeto(['Thus,', our, findings, may, very, well, encourage, the, development, of, novel, medicines, that, specifically]), verbo([target]), complemento([and, correct, the, 'T-bet/GATA-3', imbalance, identified, in, 'ITP'])]). relacion([sujeto(['Rosiglitazone,', a, well, known, insulin, 'sensitizer,']), verbo([stimulates]), complemento([adipocyte, differentiation, via, the, activation, of, peroxisome, 'proliferator-activated', receptor, γ, '(', 'PPARγ)'])]). relacion([sujeto(['Previous', 'two-dimensional', proteomics, studies, using, 'C3H10T1/2', murine, mesenchymal, pluripotent, stem, cells, revealed, that, prolyl, hydroxylase, domain, protein, '(', 'PHD)', levels, significantly]), verbo([increased]), complemento([during, 'rosiglitazone-induced', adipocyte, differentiation, '(', 'RIAD)'])]). relacion([sujeto(['Three', 'PHD', isoforms, '(', 'PHD1,', 2, ',', and, 3, ')', were]), verbo([found]), complemento([to, be, 'up-regulated', in, 'C3H10T1/2', cells, during, 'RIAD,', whereas, 'PHD', knockdown, and, treatment, with, 'PHD', inhibitors, '(', dimethyloxalyl, glycine, or, 'ethyl-3,4-dihydroxybenzoate)', blocked, 'RIAD'])]). relacion([sujeto(['PHD', inhibition, was]), verbo([found]), complemento([to, be, associated, with, increases, in, the, levels, of, 'anti-adipogenic', proteins, such, as, 'GATA-3,', 'KLF-2,', and, transcriptional, coactivator, with, 'PDZ', binding, motif, '(', 'TAZ),', with, their, reduced, 'ubiquitination,', suggesting, that, 'PHDs', evoke, the, 'ubiquitination/proteasomal', degradation, of, 'anti-adipogenic', proteins])]). relacion([sujeto(['On', the, other, 'hand,', 'MG-132', '(', a, proteasomal, 'inhibitor)']), verbo([prevented]), complemento([the, degradation, of, 'anti-adipogenic', proteins, and, retarded, 'RIAD'])]). relacion([sujeto(['Furthermore,', putative, 'PPARγ']), verbo([binding]), complemento([sites, were, identified, in, the, promoter, region, of, 'PHDs', by, 'ChIP-PCR,', implying, that, rosiglitazone, may, induce, 'PHD', 'up-regulation', directly, by, 'PPARγ', activation])]). relacion([sujeto(['Consistent', with, in, vitro, 'results,', oral, administration, of, rosiglitazone, to, 'ob/ob', mice, for, 2, weeks]), verbo([increased]), complemento([adipose, 'PHD', levels, and, decreased, 'anti-adipogenic', protein, levels, by, increasing, their, ubiquitination])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, rosiglitazone, increases, 'PHD', expression, in, a, 'PPARγ-dependent', manner, and, that, this, leads, to, the, commitment, of, 'anti-adipogenic', proteins, to, the, 'ubiquitination-proteasomal', pathway, and, to, the, subsequent, induction, of, adipocyte, differentiation])]). relacion([sujeto(['To', better, understand, the, mechanisms]), verbo([regulating]), complemento([placental, development, and, gene, 'expression,', we, characterized, the, transcriptome, of, term, placenta, from, 20, healthy, women, with, uncomplicated, pregnancies, using, 'RNA-seq'])]). relacion([sujeto(['To', identify, genes, that, were, highly]), verbo([expressed]), complemento([and, unique, to, the, placenta, we, compared, placental, 'RNA-seq', data, to, data, from, 7, other, tissues, '(', 'adipose,', 'breast,', 'hear,', 'kidney,', 'liver,', 'lung,', and, smooth, 'muscle)', and, identified, several, genes, novel, to, placental, biology, '(', 'QSOX1,', 'DLG5,', and, 'SEMA7A)'])]). relacion([sujeto(['Semi-quantitative', 'RT-PCR', confirmed, the, 'RNA-seq', results, and, immunohistochemistry, indicated, these, proteins, were, highly]), verbo([expressed]), complemento([in, the, placental, syncytium])]). relacion([sujeto(['We', identified, 'FOXO4,', 'GATA3,', and, 'WNT7A', to, be, amongst, the, highest]), verbo([expressed]), complemento([members, of, these, families])]). relacion([sujeto(['Overall,', these, findings]), verbo([provide]), complemento([a, new, reference, for, understanding, of, placental, transcriptome, and, can, aid, in, the, identification, of, novel, pathways, regulating, placenta, physiology, that, may, be, dysregulated, in, placental, disease])]). relacion([sujeto(['In', 'vertebrates,', six, 'GATA', transcription, 'factors,', 'GATA1', through, 'GATA6,']), verbo([have]), complemento([been, identified, and, 'GATA1-3', is, known, to, be, involved, in, hematopoietic, 'developments,', while, 'GATA4-6', play, roles, in, cardiac, and, endoderm, developments])]). relacion([sujeto(['Recently,', we, and, others]), verbo([have]), complemento([found, that, 'GATA2', and, 'GATA3', found, in, the, trophectoderm, plays, a, role, in, gene, expression, specific, to, this, cell, 'type,', but, 'GATA4-6', have, not, been, well, characterized, in, early, embryonic, developments])]). relacion([sujeto(['In', ovine, 'conceptuses,', 'GATA4,', 5, and, 6, transcripts, were, present, on, days, 15, ',', 17, and, 21, '(', day, 0, =, day, of, 'mating),', and, high, 'GATA5', and, 6, mRNAs, were]), verbo([found]), complemento([on, day, 21, ',', most, of, which, were, localized, in, the, trophectoderm, and, endoderm])]). relacion([sujeto(['Moreover,', minute, and, substantial, 'GATA4', and, 5, mRNAs, were]), verbo([found]), complemento([in, days, 15, and, 21, uterine, 'endometria,', respectively])]). relacion([sujeto(['Mafb']), verbo([acts]), complemento([in, 'SGNs', to, drive, differentiation, of, the, large, postsynaptic, density, '(', 'PSD)', characteristic, of, the, ribbon, synapse])]). relacion([sujeto(['In', 'Mafb', mutant, 'mice,', 'SGNs', fail, to, develop, normal, 'PSDs,']), verbo([leading]), complemento([to, reduced, synapse, number, and, impaired, auditory, responses])]). relacion([sujeto(['Conversely,']), verbo([increased]), complemento(['Mafb', accelerates, synaptogenesis])]). relacion([sujeto(['Moreover,', 'Mafb', is, responsible, for]), verbo([executing]), complemento([one, branch, of, the, 'SGN', differentiation, program, orchestrated, by, the, 'Gata3', transcriptional, network])]). relacion([sujeto(['Type', 2, innate, lymphoid, cells, '(', 'ILC2s,', 'nuocytes,', 'NHC)']), verbo([require]), complemento(['RORA', and, 'GATA3', for, their, development])]). relacion([sujeto(['We', show, that, human, 'ILC2s']), verbo([express]), complemento([skin, homing, receptors, and, infiltrate, the, skin, after, allergen, 'challenge,', where, they, produce, the, type, 2, cytokines, 'IL-5', and, 'IL-13'])]). relacion([sujeto(['Skin-derived', 'ILC2s']), verbo([express]), complemento([the, 'IL-33', receptor, 'ST2,', which, is, 'up-regulated', during, 'activation,', and, are, enriched, in, lesional, skin, biopsies, from, atopic, patients])]). relacion([sujeto(['Signaling', via, 'IL-33']), verbo([induces]), complemento([type, 2, cytokine, and, amphiregulin, 'expression,', and, increases, 'ILC2', migration])]). relacion([sujeto(['Furthermore,', we, demonstrate, that, 'E-cadherin', ligation, on, human, 'ILC2', dramatically]), verbo([inhibits]), complemento(['IL-5', and, 'IL-13', production])]). relacion([sujeto(['ILC2', may, contribute, to]), verbo([increases]), complemento([in, type, 2, cytokine, production, in, the, absence, of, the, suppressive, 'E-cadherin', ligation, through, this, novel, mechanism, of, barrier, sensing])]). relacion([sujeto(['Using', 'Rag1(-/-)', and, 'RORα-deficient', 'mice,', we, confirm, that, 'ILC2s', are, present, in, mouse, skin, and]), verbo([promote]), complemento(['AD-like', inflammation])]). relacion([sujeto(['To']), verbo([report]), complemento([on, the, clinicopathological, features, of, 20, cases, of, microcystic, urothelial, bladder, carcinoma])]). relacion([sujeto(['The', cysts, were, lined, by, 'urothelial,', low, columnar, cells, or, by, a, single, layer, of, flattened, epithelium, of, 'low-intermediate']), verbo([nuclear]), complemento([grade])]). relacion([sujeto(['The', in, vitro, immunomodulatory, assay, revealed, that, 'LCP50W']), verbo([promoted]), complemento([the, proliferation, of, mouse, splenocytes, and, enhanced, the, cytotoxicity, of, 'NK', cells])]). relacion([sujeto(['LCP50W', boosted, the, secretion, of, 'Th1', cytokine, 'IFN-γ', while, it]), verbo([inhibited]), complemento([the, secretion, of, 'Th2', cytokine, 'IL-4;', it, also, enhanced, the, expression, of, 'T-bet', while, it, inhibited, the, expression, of, 'GATA-3'])]). relacion([sujeto(['Additionally,', 'LCP50W']), verbo([promoted]), complemento([the, development, of, cell, cycle, toward, the, 'S', phase])]). relacion([sujeto(['Recent', studies, indicate, that, some, of, the, effector, subsets]), verbo([have]), complemento([plasticity])]). relacion([sujeto(['Here,', we, used, an, 'EAE', model, and]), verbo([found]), complemento([that, 'Th17', cells, deficient, in, the, transcription, factor, 'BCL11B', upregulated, the, 'Th2-associated', proteins, 'GATA3', and, 'IL-4', without, decreasing, 'RAR-related', orphan, receptor, γ, '(', 'RORγt),', 'IL-17,', and, 'GM-CSF', levels])]). relacion([sujeto(['T', helper, cell, rerouting, in, 'EAE', was, dependent, on, 'IL-4,', which]), verbo([enhanced]), complemento([retinoic, acid, '(', 'RA)', production, by, dendritic, 'cells,', which, further, induced, expression, of, 'gut-homing', receptors, 'CCR9', and, α4β7, on, 'Bcl11b-deficient', 'CD4+', 'T', cells])]). relacion([sujeto(['Furthermore,', 'IL-4', treatment, or, 'Th2', immunization, of, 'wild-type', mice, with, 'EAE']), verbo([caused]), complemento([no, alteration, in, 'Th17', cytokines, or, 'RORγt,', but, diverted, 'T', helper, cell, trafficking, to, the, 'gut,', which, improved, 'EAE', outcome, without, overt, colitis])]). relacion([sujeto(['This', 'Th17', plasticity]), verbo([has]), complemento([an, impact, on, 'trafficking,', which, is, a, critical, component, of, the, immune, response, and, may, represent, a, possible, avenue, for, treating, multiple, sclerosis])]). relacion([sujeto(['Edwardsiella', tarda, is, an, intracellular, pathogen, that]), verbo([causes]), complemento([edwardsiellosis, in, fish])]). relacion([sujeto(['Our', previous, study]), verbo([suggests]), complemento([that, 'cell-mediated', immunity, '(', 'CMI)', plays, an, essential, role, in, protection, against, 'E'])]). relacion([sujeto([tarda, to, isogenic, naïve, ginbuna, crucian, carp, to, determination, the, 'T-cell', subsets]), verbo([involved]), complemento([in, protecting, fish, from, 'E'])]). relacion([sujeto(['Moreover,', transfer, of, sensitized, 'CD8α(+)', cells, 'up-regulated', the, expression, of, genes, encoding, 'interferon-γ', '(', 'IFN-γ)', and, 'perforin,']), verbo([suggesting]), complemento([that, protective, immunity, to, 'E'])]). relacion([sujeto([tarda]), verbo([involves]), complemento(['cell-mediated', cytotoxicity, and, 'interferon-γ-mediated', induction, of, 'CMI'])]). relacion([sujeto(['These', findings]), verbo([provide]), complemento([novel, insights, into, understanding, the, role, of, 'CMI', to, intracellular, pathogens, of, fish])]). relacion([sujeto(['Transcription', factor, 'GATA']), verbo([binding]), complemento([protein, 3, '(', 'GATA3)', has, been, suggested, as, a, marker, of, urothelial, carcinoma, of, the, bladder, and, upper, urinary, tract])]). relacion([sujeto(['Its', expression, in, primary, and, metastatic, renal, tumors]), verbo([has]), complemento([not, been, fully, determined])]). relacion([sujeto(['GATA3']), verbo([nuclear]), complemento([expression, was, evaluated, in, tissue, microarrays, built, from, archival, tissues, using, immunohistochemistry])]). relacion([sujeto(['Among', 'oncocytomas,', 9, '(', 19, '%', ')', of, 47, had, some, degree, of]), verbo([nuclear]), complemento(['GATA3', expression, with, median, extent, of, 0, '%', '(', 0, '%', -, 100, '%', ')'])]). relacion([sujeto(['In', primary, 'RCCs,', 6, '(', 3, '%', ')', of, 196, had, some, degree, of]), verbo([nuclear]), complemento([expression, with, a, median, extent, of, 0, '%', '(', 0, '%', -, 100, '%', ')'])]). relacion([sujeto(['We']), verbo([found]), complemento([an, overall, lack, of, 'GATA3', expression, in, primary, and, metastatic, 'RCCs'])]). relacion([sujeto(['GATA3', is]), verbo([expressed]), complemento([in, a, minority, of, 'oncocytomas,', 'Xp11'])]). relacion([sujeto(['The', objective, of, this, study, was, to, characterize, the, cellular, and, molecular, responses, to, 'E2', in, the, mammary, glands, of, 'ACI', and, 'BN', rats, to, identify, qualitative, and, quantitative, phenotypes, that]), verbo([associate]), complemento([with, 'and/or', may, confer, differences, in, susceptibility, to, mammary, cancer])]). relacion([sujeto(['Extracellular', matrix, '(', 'ECM)']), verbo([associated]), complemento([collagen, was, evaluated, by, 'Picrosirius', 'Red', staining, and, 'Second', 'Harmonic', 'Generation', '(', 'SHG)', microscopy])]). relacion([sujeto(['Moreover,', the, epithelium, of, 'BN', rats, appeared, to, undergo, differentiation, in, response, to, 'E2,', as, evidenced, by, production, of, milk, proteins, as, well, as, luminal, ectasia, and]), verbo([associated]), complemento([changes, in, the, 'ECM'])]). relacion([sujeto(['The', 'Notch', signaling, pathway]), verbo([has]), complemento([been, recognized, as, a, key, factor, for, the, pathogenesis, of, 'T-cell', acute, lymphoblastic, leukemia, '(', 'T-ALL),', because, of, the, high, incidence, of, activating, mutations, of, 'Notch1'])]). relacion([sujeto(['Notch', inhibition, could, serve, as, a, new, treatment, strategy, for, 'T-ALL;', 'however,', the, attempts, to, perturb, 'Notch', signaling, pathways]), verbo([have]), complemento([been, unsuccessful, so, far])]). relacion([sujeto(['In', this, 'study,', we]), verbo([found]), complemento([that, proteasome, inhibitors, exert, cytotoxic, effects, on, 'T-ALL', cells, with, constitutive, activation, of, 'Notch1', to, a, similar, extent, as, myeloma, cells])]). relacion([sujeto(['The', proteasome, inhibitor, bortezomib, repressed, the, transcription, of, 'Notch1', and, downstream, effectors, including, 'Hes1,', 'GATA3,', 'RUNX3', and]), verbo([nuclear]), complemento(['factor-κB', '(', 'NF-κB)', '(', p65, and, 'p50),', coincided, with, downregulation, of, the, major, transactivator, 'Sp1', and, its, dissociation, from, 'Notch1', promoter])]). relacion([sujeto(['Our', findings]), verbo([provide]), complemento([a, molecular, basis, and, rationale, for, the, inclusion, of, proteasome, inhibitors, in, treatment, strategies, for, 'T-ALL'])]). relacion([sujeto(['Id-1', is, a, member, of, the, 'helix-loop-helix', family, of, proteins, that]), verbo([regulates]), complemento([the, activity, of, transcription, factors, to, suppress, cellular, differentiation, and, to, promote, cell, growth])]). relacion([sujeto(['Overexpression', of, 'Id-1', in, tumor, cells, correlates, with]), verbo([increased]), complemento([malignancy, and, resistance, to, chemotherapy, and, radiotherapy])]). relacion([sujeto(['We']), verbo([have]), complemento([studied, the, role, of, 'Id-1B', in, cancer, and, its, expression, in, 'healthy/malignant', lung, tissues])]). relacion([sujeto(['Moreover,', it]), verbo([increased]), complemento([the, proportion, of, cells, in, the, 'G0/G1', phase, of, the, cell, cycle, and, p27, 'levels,', while, reduced, 'phospho-Erk', and, cyclin, 'A', levels])]). relacion([sujeto(['Through', microarray, 'analysis,', we, identified, genes]), verbo([involved]), complemento([in, cell, growth, and, proliferation, that, are, specifically, deregulated, as, a, consequence, of, 'Id-1B', 'overexpression,', including, 'IGF2,', 'BMP4,', 'Id2,', 'GATA3,', 'EREG', and, 'AREG'])]). relacion([sujeto(['In', 'conclusion,', our, results, demonstrate, that, 'Id-1B']), verbo([decreases]), complemento([the, malignancy, of, lung, and, prostate, cancer, 'cells,', sensitizes, them, to, 'radiotherapy-induced', cell, 'death,', and, counteracts, the, protumorigenic, role, of, the, classical, form, of, 'Id-1'])]). relacion([sujeto(['CtBP1', epidermis, displayed, 'hyperproliferation,']), verbo([loss]), complemento([of, 'E-cadherin,', and, failed, terminal, differentiation])]). relacion([sujeto(['Known', 'CtBP1']), verbo([target]), complemento([genes, associated, with, these, 'processes,', e])]). relacion([sujeto(['CtBP1', pups, also, exhibited, a, hair]), verbo([loss]), complemento([phenotype])]). relacion([sujeto(['We']), verbo([found]), complemento([that, expression, of, the, 'Distal-less', 3, '(', 'Dlx3),', a, critical, regulator, of, hair, follicle, differentiation, and, 'cycling,', was, decreased, in, 'K5'])]). relacion([sujeto(['Molecular', studies, revealed, that, 'CtBP1', directly]), verbo([suppressed]), complemento(['Dlx3', transcription])]). relacion([sujeto(['CtBP1', mice, displayed, abnormal, hair, follicles, with]), verbo([decreased]), complemento([expression, of, 'Dlx3', downstream, targets, 'Gata3,', 'Hoxc13,', and, hair, keratins])]). relacion([sujeto(['In', 'summary,', this, 'CtBP1', transgenic, model]), verbo([provides]), complemento([in, vivo, evidence, for, certain, 'CtBP1', functions, predicted, from, in, vitro, 'studies,', 'reveals--to', our, 'knowledge--previously', unreported, functions, and, transcriptional, activities, of, 'CtBP1', in, the, context, of, 'epithelial-mesenchymal', 'interplay,', and, suggests, that, 'CtBP1', has, a, pathogenic, role, in, hair, follicle, morphogenesis, and, differentiation])]). relacion([sujeto(['To', analyze, the, dysregulated, genes, among, the, differentially]), verbo([expressed]), complemento([genes, in, 41, nasopharyngeal, biopsy, samples, and, identify, their, protective, transcriptional, factors])]). relacion([sujeto(['The', differentially]), verbo([expressed]), complemento([gene, profiles, were, obtained, by, analyzing, both, types, 'I', and, 'II', nasopharyngeal, carcinoma, '(', 'NPC_I', and, 'NPC_II,', 'respectively)', using, 'EXCEL', and, 'Bioinformatics', tools])]). relacion([sujeto(['The', transcriptional, factors, were, further, studied, only, when, '(', 1, ')', the, difference, in, the]), verbo([binding]), complemento([sites, of, the, differentially, expressed, genes, between, 'NPC_I', and, 'NPC_II', groups, was, statistically, 'significant,', '(', 2, ')', the, expressions, of, the, transcription, factors, were, correlated, with, the, gene, expressions, in, the, 'samples,', and, '(', 3, ')', the, transcription, factors, affected, at, least, 40, '%', of, the, expression, of, the, related, genes])]). relacion([sujeto(['In', 'NPC_I', 'samples,', 80, transcription, factors, were]), verbo([found]), complemento([to, be, 'up-regulated,', in, which, 'RUNX3,', 'GATA3,', 'NR3C1,', 'NRF1,', 'RXRA,', 'SMAD7,', 'TBP,', and, 'ZBTB6', were, positive, factors, and, 'HLF', and, 'MTF1', were, negative, 'factors,', involved, in, the, regulation, of, the, genes, in, 'T', cell, receptor, signaling, pathway])]). relacion([sujeto(['No', eligible, transcription, factors, were]), verbo([found]), complemento([in, association, with, 'down-regulated', genes, in, 'NPC_I', compared, to, 'NPC_II', gene, expression, profiles])]). relacion([sujeto(['The', 'over-expressed', genes, in, 'NPC_I', are, mainly, related, to, immune, 'responses,', and, we]), verbo([found]), complemento([8, positive, factors, and, 2, negative, factors, that, regulate, the, genes, in, 'T', cell, receptor, signaling, pathway])]). relacion([sujeto(['The', 10, transcription, factors, may, serve, as, potential, therapeutic]), verbo([targets]), complemento([for, 'NPC_I'])]). relacion([sujeto(['We', failed, to, identify, any, transcription, factors]), verbo([associated]), complemento([with, 'down-regulated', genes, in, 'NPC_I', relative, to, 'NPC_II', possibly, as, a, result, of, multiple, factors, that, affect, the, differential, gene, expressions, in, 'NPC_II', including, the, transcription, 'factors,', 'DNA', phosphorylation, and, 'modification,', chromosome, variation, and, environmental, factors])]). relacion([sujeto(['National', 'Surgical', 'Adjuvant', 'Breast', and, 'Bowel', 'Project', '(', 'NSABP)', trial, 'B-31']), verbo([suggested]), complemento([the, efficacy, of, adjuvant, 'trastuzumab,', even, in, 'HER2-negative', breast, cancer])]). relacion([sujeto(['This']), verbo([finding]), complemento([prompted, us, to, develop, a, predictive, model, for, degree, of, benefit, from, trastuzumab, using, archived, tumor, blocks, from, 'B-31'])]). relacion([sujeto(['Eight', predictive, genes]), verbo([associated]), complemento([with, 'HER2', '(', 'ERBB2,', 'c17orf37,', 'GRB7)', or, 'ER', '(', 'ESR1,', 'NAT1,', 'GATA3,', 'CA12,', 'IGF1R)', were, selected, for, model, building])]). relacion([sujeto(['We', developed, a, gene, 'expression-based', predictive, model, for, degree, of, benefit, from, trastuzumab, and, demonstrated, that, 'HER2-negative', tumors, belong, to, the, moderate, benefit, 'group,', thus]), verbo([providing]), complemento([justification, for, testing, trastuzumab, in, 'HER2-negative', patients, '(', 'NSABP', 'B-47)'])]). relacion([sujeto(['Contact', hypersensitivity, '(', 'CHS)', mouse, model]), verbo([induced]), complemento([by, 2, ',', 4, -, dinitrofluorobenzene, '(', 'DNFB)', is, thought, to, be, a, 'T', helper, 1, '(', 'Th1)-dominant', response, and, used, for, investigating, 'anti-inflammatory', and, immunosuppressive, agents])]). relacion([sujeto(['However,', it, is, hardly, used, for, screening, 'large-scale', drugs, because, of, the, large, number, of, animals, and, complex, mechanisms]), verbo([involved]), complemento(['in-vivo'])]). relacion([sujeto(['In', this, 'study,', we, focused, on, whether, 'T', lymphocytes, from, 'CHS', mouse, model, could]), verbo([maintain]), complemento([the, state, of, immune, response, 'in-vitro', and, explored, a, suitable, time, for, drugs, screening])]). relacion([sujeto(['Then,', we, detected, the, effects, of, dexamethasone, '(', 'DEX),', cyclosporine, 'A', '(', 'CsA)', and, mycophenolate, mofetil, '(', 'MMF)', on, 'T', lymphocytes, 'in-vitro,', and, the, data, displayed, that, these, immunosuppressive, drugs, could, all]), verbo([inhibit]), complemento([the, proliferation, of, 'T', lymphocytes, significantly])]). relacion([sujeto(['These', findings]), verbo([suggested]), complemento([that, 'T', lymphocytes, from, 'CHS', mice, could, mimic, a, similar, immune, response, 'in-vitro,', and, 'it\'s', also, a, suitable, method, for, screening, 'anti-inflammatory', and, immunosuppressive, agents])]). relacion([sujeto(['After', antigen, encounter, by, 'CD4(+)', 'T cells,', polarizing, cytokines]), verbo([induce]), complemento([the, expression, of, master, regulators, that, control, differentiation])]). relacion([sujeto(['Inactivation', of, the, histone, methyltransferase, 'Ezh2', was]), verbo([found]), complemento([to, specifically, enhance, 'T', helper, 1, '(', 'Th1)', and, 'Th2', cell, differentiation, and, plasticity])]). relacion([sujeto(['Ezh2', directly]), verbo([bound]), complemento([and, facilitated, correct, expression, of, 'Tbx21', and, 'Gata3', in, differentiating, 'Th1', and, 'Th2', 'cells,', accompanied, by, substantial, trimethylation, at, lysine, 27, of, histone, 3, '(', 'H3K27me3)'])]). relacion([sujeto(['In', 'addition,', 'Ezh2', deficiency, resulted, in, spontaneous, generation, of, discrete, 'IFN-γ', and, 'Th2', 'cytokine-producing', populations, in, nonpolarizing, 'cultures,', and, under, these, conditions, 'IFN-γ', expression, was, largely, dependent, on]), verbo([enhanced]), complemento([expression, of, the, transcription, factor, 'Eomesodermin'])]). relacion([sujeto(['In vivo,']), verbo([loss]), complemento([of, 'Ezh2', caused, increased, pathology, in, a, model, of, allergic, asthma, and, resulted, in, progressive, accumulation, of, memory, phenotype, 'Th2', cells])]). relacion([sujeto(['Previous', data, showed, that, the, predominance, of, intraglomerular, 'T-bet', or, 'GATA3', is, correlated, with, different, mechanisms, of, 'rejection,']), verbo([suggesting]), complemento([that, the, ratio, of, 'T-bet/GATA3', might, be, used, to, distinguish, 'antibody-mediated', rejection, '(', 'ABMR)', and, 'T-cell-mediated', rejection, '(', 'TCMR)'])]). relacion([sujeto(['Both', intraglomerular, 'T-bet-', and, 'GATA3-expressing', cells, were]), verbo([increased]), complemento([during, acute, rejection])]). relacion([sujeto(['Our', data]), verbo([suggested]), complemento([that, intraglomerular, predominance, of, 'T-bet', over, 'GATA3', might, be, used, as, diagnosis, maker, of, 'ABMR', in, addition, to, 'C4d,', especially, in, 'C4d-negative', cases])]). relacion([sujeto(['TGFβ']), verbo([promotes]), complemento([the, lung, metastasis, of, 'basal-like', '(', but, not, the, 'luminal-like)', breast, cancer])]). relacion([sujeto(['Here,', we, demonstrated, that, 'fascin,', a, 'pro-metastasis', actin, bundling, 'protein,', was, a, direct]), verbo([target]), complemento([of, the, canonical, 'TGFβ-Smad4', signaling, pathway, in, 'basal-like', breast, cancer, cells])]). relacion([sujeto(['TGFβ', and, 'Smad4']), verbo([induced]), complemento([fascin, overexpression, by, directly, binding, to, a, 'Smad', binding, element, on, the, fascin, promoter])]). relacion([sujeto(['When', ectopically]), verbo([expressed]), complemento([in, 'basal-like', breast, cancer, 'cells,', 'GATA-3', abrogated, 'TGFβ-', and, 'Smad4-mediated', overexpression, of, fascin, and, other, 'TGFβ', response, 'genes,', invadopodium, 'formation,', cell, 'migration,', and, 'invasion,', suggesting, suppression, of, the, canonical, 'TGFβ-Smad', signaling, axis])]). relacion([sujeto(['Mechanistically,', 'GATA3', abrogated, the, canonical, 'TGFβ-Smad', signaling, by, abolishing, interactions, between, 'Smad4', and, its, 'DNA']), verbo([binding]), complemento(['elements,', potentially, through, physical, interactions, between, the, 'N-terminal', of, 'GATA3', and, 'Smad3/4', proteins])]). relacion([sujeto(['Our', findings]), verbo([provide]), complemento([mechanistic, insight, into, how, 'TGFβ-mediated', cell, motility, and, invasiveness, are, differentially, regulated, in, breast, cancer])]). relacion([sujeto(['Zinc', oxide, nanoparticles, '(', 'ZNPs)']), verbo([have]), complemento([been, used, in, dietary, supplements, and, may, cause, an, immunomodulatory, effect])]). relacion([sujeto(['The', serum, levels, of, 'OVA-specific', 'IgG1', and, 'IgE', were]), verbo([found]), complemento([significantly, enhanced, by, treatment, with, 'ZNPs', over, control])]). relacion([sujeto(['An']), verbo([increased]), complemento([level, of, 'IL-2,', 'IL-4,', 'IL-6,', 'IL-17', and, decreased, level, of, 'IL-10', and, 'TNF-α', in, splenocytes, administered, with, 'ZNPs', were, observed, in, comparison, with, control])]). relacion([sujeto(['The', 'ZNPs', and, 'OVA-stimulated', 'T', lymphocytes, showed]), verbo([enhanced]), complemento([proliferation, compared, with, control])]). relacion([sujeto(['The', lungs, and, spleen, had]), verbo([increased]), complemento([eosinophils, and, mast, cell, numbers])]). relacion([sujeto(['Also,', myeloperoxidase, activity, in, lungs, was]), verbo([found]), complemento([to, be, increased, by, 2.5, -, fold, in, the, case, of, 'ZNPs', and, 3.75, -, fold, increase, in, 'ZNPs/OVA,', whereas, in, 'intestine,', there, was, significant, increase, in, both, the, groups])]). relacion([sujeto(['Collectively,', these, data, indicate, that, systemic, exposure, to, a, single, administration, of, 'ZNPs', could]), verbo([enhance]), complemento([subsequent, 'antigen-specific', immune, 'reactions,', including, the, serum, production, of, 'antigen-specific', 'antibodies,', and, the, functionality, of, 'T', cells])]). relacion([sujeto(['T-box']), verbo([expressed]), complemento([in, 'T', cells, '(', 'TBET)', and, guanine, adenine, thymine, adenine, 'sequence-binding', protein, 3, '(', 'GATA3)', play, important, roles, in, the, differentiation, of, 'Th1', and, 'Th2', 'subsets,', which, contributes, to, the, progression, of, acute, coronary, syndrome, '(', 'ACS)'])]). relacion([sujeto(['The', 'TBET/GATA3', mRNA, ratio, was, elevated, dramatically, in, patients, with, acute, myocardial, infarction, '(', 'AMI)', and, exhibited, biphasic, 'M-shaped']), verbo([release]), complemento([kinetics, with, two, distinct, peaks])]). relacion([sujeto(['The', biphasic, 'M-shaped']), verbo([release]), complemento([kinetics, was, more, likely, to, reflect, pathophysiological, changes, rather, than, treatment, effects])]). relacion([sujeto(['In', a, transcriptomic, survey, aimed, at, identifying, molecular, factors]), verbo([associated]), complemento([with, lymph, node, involvement, of, ductal, breast, 'cancer,', we, found, that, luminal, 'differentiation,', assessed, by, the, expression, of, estrogen, receptor, '(', 'ER)', 'and/or', progesterone, receptor, '(', 'PR)', and, 'GATA3,', was, only, infrequently, lost, in, 'node-positive', primary, tumors, and, in, matched, lymph, node, metastases])]). relacion([sujeto(['These', observations]), verbo([suggest]), complemento([that, loss, of, luminal, differentiation, is, not, a, major, factor, driving, the, ability, of, breast, cancer, cells, to, colonize, regional, lymph, nodes])]). relacion([sujeto(['Intragastric', immunization, with, recombinant, chimeric, 'immunogen,', 'SBR-CTA2/B,', constructed, from, the, 'saliva-binding', region, '(', 'SBR)', of, 'Streptococcus', mutans, antigen, 'AgI/II', and, the, 'A2/B', subunits, of, cholera, toxin, '(', 'CT)']), verbo([induces]), complemento([salivary, and, circulating, antibodies, against, 'S'])]). relacion([sujeto(['We', previously]), verbo([found]), complemento([that, 'SBR-CTA2/B', activated, dendritic, cells, '(', 'DC)', in, the, 'Peyer\'s', patches, '(', 'PP)', and, mesenteric, lymph, nodes, '(', 'MLN)'])]). relacion([sujeto(['To', identify, the, cells]), verbo([involved]), complemento([in, the, intestinal, uptake, of, 'SBR-CTA2/B', and, the, initiation, of, immune, 'responses,', mice, were, immunized, intragastrically, with, 'fluorescein-labeled', 'SBR-CTA2/B', or, 'SBR,', and, intestinal, cells, were, examined, by, imaging, flow, cytometry, after, fluorescent, staining, for, cell, surface, markers])]). relacion([sujeto(['By', 16, 'h,', 'CD103(+)', and, 'CD11c(+)', 'DC', containing, 'fluorescein-labeled', 'SBR-CTA2/B', were]), verbo([found]), complemento([in, 'MLN', and, showed, upregulation, of, the, chemokine, receptor, 'CCR7'])]). relacion([sujeto(['Large', numbers, of, 'SBR-CTA2/B-containing', 'DC', were]), verbo([found]), complemento([interacting, with, 'CD4(+)', '(', 'T', 'helper)', 'cells,', which, costained, for, nuclear, transcription, factors, 'T-bet', or, 'RORγt,', identifying, them, as, 'Th1', or, 'Th17', cells])]). relacion([sujeto(['In', 'contrast,', 'SBR-containing', 'CD11c(+)', 'DC']), verbo([interacted]), complemento([preferentially, with, 'GATA3(+)', '(', 'Th2)', cells])]). relacion([sujeto(['No', 'SBR-', or, 'SBR-CTA2/B-containing', 'DC', were]), verbo([found]), complemento([interacting, with, 'Foxp3(+)', '(', 'T', 'regulatory)', cells])]). relacion([sujeto(['We', conclude, that, the, coupling, of, 'SBR', to, 'CTA2/B']), verbo([enhances]), complemento([its, immunogenicity, by, promoting, uptake, by, 'DC', in, both, 'PP', and, 'LP', and, that, these, 'antigen-containing', 'DC', migrated, to, 'MLN', and, interacted, preferentially, with, 'Th1', and, 'Th17', cells, to, induce, active, immune, responses])]). relacion([sujeto(['Unique', to, this, approach, is, that, each, driver, gene, is]), verbo([associated]), complemento([with, several, gene, modules, that, are, believed, to, be, altered, by, the, driver])]). relacion([sujeto(['Thirty', candidate, drivers, were]), verbo([found]), complemento([in, the, male, breast, cancers, and, 67, in, the, female, breast, cancers])]). relacion([sujeto(['In', 'contrast,', only, three, known, cancer, genes, were]), verbo([found]), complemento([among, male, breast, 'cancers;', 'MAP2K4,', 'LHP,', and, 'ZNF217'])]). relacion([sujeto(['Many', of, the, candidate, drivers, identified, are, known, to, be]), verbo([involved]), complemento([in, processes, associated, with, 'tumorigenesis,', including, 'proliferation,', invasion, and, differentiation])]). relacion([sujeto(['One', of, the, modules, identified, in, male, breast, cancer, was]), verbo([regulated]), complemento([by, 'THY1,', a, gene, involved, in, invasion, and, related, to, 'epithelial-mesenchymal', transition])]). relacion([sujeto(['Another', module, identified, among, male, breast, 'cancers,']), verbo([regulated]), complemento([by, 'SPAG5,', was, closely, associated, with, proliferation])]). relacion([sujeto(['Our', data, indicate, that, male, and, female, breast, cancers, display, highly, different, landscapes, of, candidate, driver, 'genes,', as, only, a, few, genes, were]), verbo([found]), complemento([in, common, between, the, two])]). relacion([sujeto(['Consequently,', the, pathobiology, of, male, breast, cancer, may, differ, from, that, of, female, breast, cancer, and, can, be]), verbo([associated]), complemento([with, differences, in, 'prognosis;', men, diagnosed, with, breast, cancer, may, consequently, require, different, management, and, treatment, strategies, than, women])]). relacion([sujeto(['We', also, studied, 1, ',', 481, 'DNA', samples, obtained, from, saliva, of, subjects, from, the, 'USA,', 918, children, from, 'Brazil,', and, 275, children, from, 'Turkey,', in, order, to, follow, up, the, results]), verbo([found]), complemento([in, the, 'Filipino', families])]). relacion([sujeto([1, software, to, determine, if, the, nucleotide, changes, of, the]), verbo([associated]), complemento(['SNPs', changed, the, prediction, of, the, presence, of, 'transcription-binding', site, sequences, and, we, also, analyzed, the, gene, expression, of, the, genes, selected, based, on, binding, predictions])]). relacion([sujeto([1, that, is, highly]), verbo([conserved]), complemento([in, mammals])]). relacion([sujeto(['Statistically', significant, association, with, high, caries, experience, was]), verbo([found]), complemento([for, 11, markers, in, 13, q31])]). relacion([sujeto(['In', the, populations, used, for, 'follow-up', 'purposes,', associations, were]), verbo([found]), complemento([between, high, caries, experience, and, a, subset, of, these, markers])]). relacion([sujeto(['Regarding', the, prediction, of, the, 'transcription-binding', 'site,', the, base, change, of, the, 'SNP', rs17074565, was]), verbo([found]), complemento([to, change, the, 'predicted-binding', of, genes, that, could, be, involved, in, the, pathogenesis, of, caries])]). relacion([sujeto(['When', the, sequence]), verbo([has]), complemento([the, allele, 'C', of, 'rs17074565,', the, potential, transcription, factors, binding, the, sequence, are, 'GR', and, 'GATA1'])]). relacion([sujeto(['When', the, subject, carries, the, 'G', allele, of, 'rs17074565,', the, potential, transcription, factor, predicted, to]), verbo([bind]), complemento([to, the, sequence, is, 'GATA3'])]). relacion([sujeto(['No', mutations, were]), verbo([found]), complemento([in, the, highly, conserved, sequence])]). relacion([sujeto(['The', rs17074565, is, located, in, an, intergenic, region, and, is, predicted, to, disrupt, the]), verbo([binding]), complemento([sites, of, two, different, transcription, factors, that, might, be, involved, with, caries, experience])]). relacion([sujeto(['We', predicted, that, in, the, absence, of, 'IL-6,', mice, infected, with, the, gastrointestinal, helminth, 'Heligmosomoides', polygyrus, would, show, reduced, 'Th17-cell', 'responses,', but, also]), verbo([enhanced]), complemento(['Treg-cell', activity, and, consequently, greater, susceptibility])]). relacion([sujeto(['Resistance', did, correlate, with, significant, changes, to, the]), verbo([associated]), complemento(['Treg-cell', phenotype, 'however,', as, 'IL-6-deficient', mice, displayed, reduced, expression, of, 'Foxp3,', 'Helios,', and, 'GATA-3,', and, enhanced, production, of, cytokines, within, the, 'Treg-cell', population])]). relacion([sujeto(['Thus,', in, 'vivo,', 'IL-6', limits, the, 'Th2', 'response,', modifies, the, 'Treg-cell', 'phenotype,', and]), verbo([promotes]), complemento([host, susceptibility, following, helminth, infection])]). relacion([sujeto(['Recent', data]), verbo([suggest]), complemento([that, 'West', 'African', men, also, have, elevated, risk, for, prostate, cancer, relative, to, 'European', men])]). relacion([sujeto([3, were]), verbo([associated]), complemento([with, high, 'Gleason', score, '(', '≥7)', 'cancers,', the, strongest, of, which, was, a, missense, 'SNP', in, 'PCDHA1', '(', 'rs34575154,', 'p = 3'])]). relacion([sujeto([9.5e-7, ')', were]), verbo([associated]), complemento([with, low, 'Gleason', score, '(', &, 'lt;7)', cancers])]). relacion([sujeto(['Of', the, 90, prostate, cancer, loci]), verbo([reported]), complemento([from, studies, of, men, of, 'European,', 'Asian', or, 'African-American', 'ancestry,', we, were, able, to, test, 81, in, the, 'Ghana', 'Prostate', 'Study,', and, 10, of, these, replicated, at, 'p < 0'])]). relacion([sujeto(['We', herein]), verbo([found]), complemento([that, 'Gata3', associates, with, 'RuvB-like', protein, 2, '(', 'Ruvbl2)', and, represses, the, expression, of, a, 'CDK', 'inhibitor,', 'cyclin-dependent', kinase, inhibitor, 2, c, '(', 'Cdkn2c)', to, facilitate, the, proliferation, of, 'Th2', cells])]). relacion([sujeto(['Gata3', directly]), verbo([bound]), complemento([to, the, 'Cdkn2c', locus, in, an, 'Ruvbl2-dependent', manner])]). relacion([sujeto(['The', defect, in, the, proliferation, of, 'Gata3-deficient', 'Th2', cells, is, rescued, by, the, knockdown, of, 'Cdkn2c,', indicating, that, 'Cdkn2c', is, a, key, molecule]), verbo([involved]), complemento([in, the, 'Gata3-mediated', induction, of, 'Th2', cell, proliferation])]). relacion([sujeto(['Ruvbl2-knockdown', 'Th2', cells, showed]), verbo([decreased]), complemento(['antigen-induced', expansion, and, caused, less, airway, inflammation, in, vivo])]). relacion([sujeto(['We', therefore]), verbo([have]), complemento([identified, a, functional, 'Gata3/Ruvbl2', complex, that, regulates, the, proliferation, of, differentiating, 'Th2', cells, through, the, repression, of, a, 'CDK', 'inhibitor,', 'Cdkn2c'])]). relacion([sujeto(['Nasal', fibroblasts, isolated, from, the, specimens, were]), verbo([stimulated]), complemento([with, poly, 'I:C'])]). relacion([sujeto(['Nasal', fibroblasts, from, the, 'ATA', and, 'AIA', groups, showed, significantly]), verbo([enhanced]), complemento([expression, of, 'CXCL10', mRNA, and, protein, after, poly, 'I:C', stimulation, compared, with, cells, from, the, 'CRS', group, and, the, control, group, '(', normal, nasal, 'mucosa)'])]). relacion([sujeto(['Our', findings]), verbo([suggest]), complemento([that, 'CRS', associated, with, asthma, may, become, intractable, through, the, 'over-production', of, 'CXCL10', in, response, to, viral, infection])]). relacion([sujeto(['CD4(+)', 'FOXP3(+)', regulatory, 'T', '(', 'Treg)', cells, constitute, a, heterogeneous, and, plastic, 'T-cell', lineage, that, plays, a, pivotal, role, in]), verbo([maintaining]), complemento([immune, homeostasis, and, immune, tolerance])]). relacion([sujeto(['However,', the, fate, of, human, 'Treg', cells, after]), verbo([loss]), complemento([of, 'FOXP3', expression, and, the, epigenetic, mechanisms, contributing, to, such, a, phenotype, switch, remain, to, be, fully, elucidated])]). relacion([sujeto(['Surprisingly,', reprogramming, of, 'Treg', cells, was]), verbo([associated]), complemento([with, differential, histone, 'modifications,', as, evidenced, by, decreased, abundance, of, permissive, 'H3K4me3', within, the, 'down-regulated', 'Treg', cell, signature, 'genes,', such, as, 'FOXP3,', 'CTLA4', and, 'LRRC32', 'loci,', and, increased, abundance, of, 'H3K4me3', within, the, 'Th2-associated', 'genes,', such, as, 'IL4', and, 'IL5;', 'however,', the, 'H3K27me3', modification, profile, was, not, significantly, different, between, the, two, subpopulations])]). relacion([sujeto(['In', 'conclusion,', this, study, revealed, that]), verbo([loss]), complemento([of, 'FOXP3', expression, from, human, 'Treg', cells, during, in, vitro, expansion, can, induce, reprogramming, to, a, 'T', helper, cell, phenotype, with, a, gene, expression, signature, dominated, by, 'Th2', 'lineage-associated', 'genes,', and, that, this, cell, type, conversion, may, be, mediated, by, histone, methylation, events])]). relacion([sujeto(['It']), verbo([has]), complemento([been, suggested, to, be, useful, in, the, evaluation, of, carcinomas, of, mammary, or, urothelial, origin, or, metastatic, 'carcinomas,', but, its, distribution, in, normal, and, neoplastic, tissues, is, incompletely, mapped])]). relacion([sujeto(['GATA3', was]), verbo([expressed]), complemento([in, 'trophoblast,', fetal, and, adult, 'epidermis,', adult, mammary, and, some, salivary, gland, and, sweat, gland, ductal, 'epithelia,', 'urothelia,', distal, nephron, in, developing, and, adult, 'tissues,', some, prostatic, basal, 'cells,', and, subsets, of, 'T', lymphocytes])]). relacion([sujeto(['It', was]), verbo([expressed]), complemento([stronger, in, fetal, than, in, adult, mesothelia, and, was, absent, in, respiratory, and, gastrointestinal, epithelia])]). relacion([sujeto(['In', epithelial, 'neoplasms,', 'GATA3', was]), verbo([expressed]), complemento([in, &, 'gt;90%', of, primary, and, metastatic, ductal, and, lobular, carcinomas, of, the, 'breast,', 'urothelial,', and, cutaneous, basal, cell, carcinomas, and, trophoblastic, and, endodermal, sinus, tumors])]). relacion([sujeto(['Common', positivity, was]), verbo([found]), complemento([in, skin, adnexal, tumors, '(', 100, '%', ')', ',', mesothelioma, '(', 58, '%', ')', ',', salivary, gland, '(', 43, '%', ')', ',', and, pancreatic, '(', 37, '%', ')', ductal, 'carcinomas,', whereas, frequency, of, expression, in, adenocarcinomas, of, 'lung,', 'stomach,', 'colon,', 'endometrium,', 'ovary,', and, prostate, was, &, 'lt;10%'])]). relacion([sujeto(['Pluripotent', stem, 'cells,', including, human, embryonic, stem, cells, '(', 'hESCs)', and]), verbo([induced]), complemento([pluripotent, stem, cells, '(', 'hiPSCs),', have, been, regarded, as, useful, sources, for, 'cell-based', transplantation, therapy])]). relacion([sujeto(['We']), verbo([report]), complemento([the, examination, of, several, hESC, lines, '(', 'NTU1', and, 'H9),', hiPSC, 'lines,', and, their, derivatives, '(', including, stem, 'cell-derived', 'hepatocytes)', for, the, expression, of, major, histocompatibility, complex, '(', 'MHC),', natural, killer, '(', 'NK)', cell, receptor, '(', 'NKp30,', 'NKp44,', 'NKp46)', 'ligand,', 'immune-related', 'genes,', human, leukocyte, antigen, '(', 'HLA)', 'haplotyping,', and, the, effects, in, functional, mixed, lymphocyte, reaction, '(', 'MLR)'])]). relacion([sujeto(['The', levels, were]), verbo([increased]), complemento([after, cotreatment, with, 'interferon-γ', 'and/or', in, vitro, differentiation])]). relacion([sujeto(['Activation', of]), verbo([responder]), complemento([lymphocytes, was, significantly, lower, by, undifferentiated, stem, cells, than, by, allogeneic, lymphocytes, in, 'MLR,', but, differentiated, 'NTU1', hESCs, induced, a, cell, 'number-dependent', lymphocyte, proliferation, comparable, with, that, by, allogeneic, lymphocytes])]). relacion([sujeto(['It', was, concluded, that, pluripotent, stem, 'cells/derivatives', are, predicted, to, be, 'immunogenic,', though, evidence]), verbo([suggests]), complemento([some, level, of, potential, immune, privilege])]). relacion([sujeto(['Type', 2, innate, lymphoid, cells, '(', 'ILC2', 'cells)']), verbo([participate]), complemento([in, host, defense, against, helminth, parasites, and, in, allergic, inflammation])]). relacion([sujeto(['Given', their, functional, relatedness, to, type, 2, helper, 'T', cells, '(', 'T(H)2', 'cells),', we, explored, whether, 'Gfi1']), verbo([acts]), complemento([as, a, shared, transcriptional, determinant, in, 'ILC2', cells])]). relacion([sujeto(['Gfi1']), verbo([promoted]), complemento([the, development, of, 'ILC2', cells, and, controlled, their, responsiveness, during, infection, with, 'Nippostrongylus', brasiliensis, and, protease, 'allergen-induced', lung, inflammation])]). relacion([sujeto(['Gfi1', '\'', 'preferentially\'']), verbo([regulated]), complemento([the, responsiveness, of, 'ILC2', cells, to, interleukin, 33, '(', 'IL-33)', by, directly, activating, 'Il1rl1,', which, encodes, the, 'IL-33', receptor, '(', 'ST2)'])]). relacion([sujeto(['Loss', of, 'Gfi1', in]), verbo([activated]), complemento(['ILC2', cells, resulted, in, impaired, expression, of, the, transcription, factor, 'GATA-3', and, a, dysregulated, 'genome-wide', effector, state, characterized, by, coexpression, of, 'IL-13', and, 'IL-17'])]). relacion([sujeto(['Our', findings, establish, 'Gfi1', as, a, shared, determinant, that, reciprocally]), verbo([regulates]), complemento([the, type, 2, and, 'IL-17', effector, states, in, cells, of, the, innate, and, adaptive, immune, systems])]). relacion([sujeto(['The', rs3824662, risk, allele, was]), verbo([associated]), complemento([with, somatic, lesions, underlying, 'Ph-like', 'ALL', '(', 'CRLF2', 'rearrangement,', 'JAK', gene, mutation, and, 'IKZF1', 'deletion)', and, with, variation, in, 'GATA3', expression])]). relacion([sujeto(['Finally,', genotype, at, the, 'GATA3', 'SNP', was, also]), verbo([associated]), complemento([with, early, treatment, response, and, risk, of, 'ALL', relapse])]). relacion([sujeto(['Our', results]), verbo([provide]), complemento([insights, into, interactions, between, inherited, and, somatic, variants, and, their, role, in, 'ALL', pathogenesis, and, prognosis])]). relacion([sujeto(['Shenghua', 'Decoction', '(', 'SHD)', is, a, 'well-known', traditional, 'Chinese', herbal, prescription, for, reducing, uterine, bleeding]), verbo([induced]), complemento([by, 'RU486', medical, abortion])]). relacion([sujeto(['The', 'Th1/Th2/Th17/Treg', paradigm, plays, an, important, role, in, achieving, 'maternal-fetal', immunotolerance, and, its, bias]), verbo([participates]), complemento([in, 'RU486-induced', abortion])]). relacion([sujeto(['Additionally,', 'Th1-type', cytokine]), verbo([inducing]), complemento([effect, was, identified, in, our, previous, study])]). relacion([sujeto(['Therefore,', it, was, hypothesized, that, 'SHD', reduced, the, uterine, bleeding, in, 'RU486', medical, abortion, by]), verbo([inducing]), complemento(['Th1/Th2/Th17/Treg', paradigm, bias])]). relacion([sujeto(['Moreover,', to, elucidate, the, mechanism, underlying, the, 'T-cell', paradigm]), verbo([regulating]), complemento([of, 'SHD,', the, mRNA, and, protein, expressions, of, 'subset-specific', transcription, factors, '(', 'T-bet,', 'GATA-3,', 'RORγt,', and, 'Foxp3)', for, the, differentiation, of, 'Th1/Th2/Th17/Treg', paradigm, in, human, decidual, 'CD4(+)', 'T', cells, were, detected, by, reverse, 'transcription-polymerase', chain, reaction, '(', 'RT-PCR)', assay, and, western, blot, analysis, respectively])]). relacion([sujeto(['SHD']), verbo([increased]), complemento([the, proportions, of, 'Th1', and, 'Th17', cells, whereas, decreased, those, of, 'Th2', and, 'Treg', cells])]). relacion([sujeto(['SHD']), verbo([promoted]), complemento([the, mRNA, as, well, as, the, protein, expressions, of, 'subset-specific', transcription, factors, for, the, differentiation, of, 'Th1', and, 'Th17', subsets, '(', 'T-bet', and, 'RORγt)', while, inhibited, those, of, 'Th2', and, 'Treg', cells, '(', 'GATA-3', and, 'Foxp3)'])]). relacion([sujeto(['Th1/Th2/Th17/Treg', paradigm, bias, was]), verbo([involved]), complemento([in, 'RU486', medical, abortion])]). relacion([sujeto(['SHD', reduced, the, uterine, bleeding, efficiently, by]), verbo([inducing]), complemento(['Th1', and, 'Th17', skews, in, the, 'maternal-fetal', of, 'RU486', medical, abortion, patients])]). relacion([sujeto(['The', penile, urethra]), verbo([has]), complemento([a, distinctive, morphology, not, yet, fully, characterized, by, immunohistochemistry])]). relacion([sujeto(['In', 'addition,', both, urothelial, and, squamous, cell, carcinomas]), verbo([have]), complemento([been, reported, in, the, penile, 'urethra,', and, the, distinction, between, these, 2, tumors, might, be, difficult])]). relacion([sujeto(['In', 'addition,', our, study]), verbo([suggests]), complemento([that, 'GATA3', and, human, papillomavirus, detection, are, useful, markers, for, distinguishing, urothelial, carcinomas, from, squamous, cell, carcinomas, of, the, penile, urethra])]). relacion([sujeto(['Gene', profile, analysis, indicates, that, the, cells, grown, on, porous, polymer, films, show]), verbo([enhanced]), complemento([expressions, of, mammary, differentiation, genes, '(', 'GATA3,', 'EMA,', and, 'INTEGB4)', but, lower, the, expression, of, mesenchymal, gene, '(', 'CALLA)'])]). relacion([sujeto(['Hormonal', stimulation, of, these, cultures, dramatically]), verbo([increases]), complemento([expression, of, progenitor, marker, gene, 'Notch1'])]). relacion([sujeto(['Importantly,', cells, grown, on, porous, 'PLGA', films, exhibit, an]), verbo([enhanced]), complemento([resistance, to, doxorubicin, treatment, in, comparison, to, 2, 'D', cultures])]). relacion([sujeto(['Responses', to, 'CMV']), verbo([have]), complemento([a, 'Th1', predominant, profile, '(', 35.6, '%', of, responding, cells, expressing, 'tbx21)', whereas, responses, to, 'Tetanus', 'Toxoid', have, a, 'Th2', biased, profile, '(', 22, '%', of, responding, cells, expressing, 'gata3),', with, unexpectedly, high, levels, of, 'Treg', cells, found, in, both, populations])]). relacion([sujeto(['Reduced', expression, of, 'TGFBR3']), verbo([has]), complemento([been, frequently, observed, in, several, types, of, human, cancers])]). relacion([sujeto(['As', a, 'result,', the, expression, of, 'TGFBR3', and, 'GATA3,', a, transcriptional, factor, of, the, 'TGFBR3', 'gene,', were]), verbo([found]), complemento([to, be, 'co-downregulated', in, 'BUC'])]). relacion([sujeto(['Moreover,', our, findings, indicated, that, 'GATA3', promoter, methylation, was, one, of, the, reasons, for, silencing, of, 'GATA3', and, 'TGFBR3', in, 'BUC,', albeit, 'TGFBR3', methylation, and, mutation, were, not]), verbo([associated]), complemento([with, reduced, expression, of, 'TGFBR3', mRNA, in, 'BUC'])]). relacion([sujeto(['In', 'summary,', our, findings]), verbo([suggest]), complemento([that, methylation, in, the, 'GATA3', promoter, region, may, inhibit, the, expression, of, 'GATA3', 'mRNA,', which, leads, to, the, reduced, expression, of, 'TGFBR3', mRNA, in, 'BUC'])]). relacion([sujeto(['GATA3']), verbo([has]), complemento([been, recognized, as, a, promising, marker, for, primary, urothelial, carcinoma, '(', 'UC),', consistently, showing, higher, expression, levels, than, urothelial, markers, thrombomodulin, and, uroplakin, 'III'])]). relacion([sujeto(['However,', expression, of, 'GATA3', in, comparison, with, 'UC-associated', markers, 'CK7', and, p63]), verbo([has]), complemento([not, been, systematically, studied])]). relacion([sujeto(['Moreover,', no, studies]), verbo([have]), complemento([been, conducted, to, establish, 'GATA3', sensitivity, in, regional, metastases])]). relacion([sujeto(['GATA3', was]), verbo([expressed]), complemento([in, 62, /, 69, '(', 90, '%', ')', primary, 'UC', and, 64, /, 69, '(', 93, '%', ')', 'metastases,', with, significantly, higher, staining, intensity, in, nodal, metastases, '(', 'P=0'])]). relacion([sujeto(['The', majority, of, positive, cases, showed, strong, diffuse]), verbo([nuclear]), complemento(['reactivity:', 75, '%', of, primary, 'UCs', and, 79, '%', of, metastases])]). relacion([sujeto(['GATA3', specificity, was, computed, in, comparison, with, its, morphologic, mimics]), verbo([expressing]), complemento(['CK7', and, 'p63,', including, 208, primary, and, 24, metastatic, tumors, from, the, 'lung,', 'cervix,', and, head, and, neck, regions])]). relacion([sujeto(['Our', findings, demonstrate, high, sensitivity, and, specificity, of, the, 'GATA3', diagnostic, 'marker,', with, not, only]), verbo([maintained]), complemento([but, increased, expression, in, regional, metastases])]). relacion([sujeto(['A', 'genome-wide', association, study, implicated, 'NKX2-5,', which, encodes, a, transcription, factor, that, is]), verbo([expressed]), complemento([in, embryonic, heart, and, 'pylorus,', in, the, pathogenesis, of, infantile, hypertrophic, pyloric, stenosis])]). relacion([sujeto(['However,', the, function, of, the, 'NKX2-5', in, pyloric, smooth, muscle, development]), verbo([has]), complemento([not, been, examined, directly])]). relacion([sujeto(['Disruption', of, 'Nkx2-5', or, 'Gata3']), verbo([causes]), complemento([severe, hypoplasia, of, this, fascicle, and, alters, pyloric, muscle, shape])]). relacion([sujeto(['Although', expression, of, 'Sox9']), verbo([requires]), complemento(['Nkx2-5', and, 'Gata3,', there, is, no, apparent, hierarchical, relationship, between, 'Nkx2-5', and, 'Gata3', during, pyloric, outer, longitudinal, muscle, development])]). relacion([sujeto(['Nkx2-5', and, 'Gata3', are, independently]), verbo([required]), complemento([for, the, development, of, a, pyloric, outer, longitudinal, muscle, 'fascicle,', which, is, required, for, pyloric, sphincter, morphogenesis, in, mice])]). relacion([sujeto(['Porphyromonas', gingivalis, can, synthesize, an, extracellular, capsule, and, different, serotypes]), verbo([have]), complemento([been, described, based, on, capsular, antigenicity])]). relacion([sujeto(['This', study, aimed, to, investigate, the, 'T-lymphocyte', responses, when]), verbo([stimulated]), complemento([with, autologous, mature, 'DCs', exposed, to, different, 'P'])]). relacion([sujeto(['Naïve', 'CD4(+)', 'T-lymphocytes', were, obtained, from, healthy, subjects, and]), verbo([stimulated]), complemento([with, autologous, 'DCs', primed, with, increasing, multiplicity, of, infections, of, the, different, 'P'])]). relacion([sujeto(['Distinct', types, of, response, were, detected, when, 'T-lymphocytes', were]), verbo([stimulated]), complemento([by, 'DCs', primed, with, the, different, 'P'])]). relacion([sujeto(['T-lymphocytes']), verbo([stimulated]), complemento([by, 'K1', or, 'K2-primed', 'DCs', elicited, higher, levels, of, 'Th1', and, 'Th17-associated', 'cytokines,', 'T-bet', and, 'RORC2', than, 'T-lymphocytes', stimulated, with, 'DCs', primed, with, the, other, serotypes])]). relacion([sujeto(['Conversely,', the, serotypes, 'K3-K5']), verbo([induced]), complemento([higher, levels, of, 'Th2-associated', cytokines, and, 'GATA-3', than, the, others])]). relacion([sujeto(['Strains', 'K1', '(', 'W83)', and, 'K2', '(', 'HG184)']), verbo([induced]), complemento([a, 'Th1/Th17', pattern, of, immune, response, and, 'K3', '(', 'A7A1-28),', 'K4', '(', 'ATCC(®49417™)', ')', ',', and, 'K5', '(', 'HG1690)', a, 'Th2', response])]). relacion([sujeto(['Allergy', is, a, complex, disease, that, is, likely, to]), verbo([involve]), complemento([dysregulated, 'CD4+', 'T', cell, activation])]). relacion([sujeto(['Here', we, propose, a, novel, methodology, to]), verbo([gain]), complemento([insight, into, how, coordinated, behaviour, emerges, between, 'disease-dysregulated', pathways, in, response, to, pathophysiological, stimuli])]). relacion([sujeto(['We', delineate, a, novel, disease, network, linking, 'T', cell, activation, to, the, complement, system, that, is, significantly, enriched, for, genes, exhibiting, correlated, gene, expression, and, 'protein-protein', 'interactions,']), verbo([suggesting]), complemento([a, tight, biological, coordination, that, is, dysregulated, in, the, disease, state, in, response, to, pollen, allergen, but, not, to, diluent])]). relacion([sujeto(['This', novel, disease, network]), verbo([has]), complemento([high, predictive, power, for, the, gene, and, protein, expression, of, the, 'Th2', cytokine, profile, '(', 'IL-4,', 'IL-5,', 'IL-10,', 'IL-13)', and, of, the, 'Th2', master, regulator, '(', 'GATA3),', suggesting, its, involvement, in, the, early, stages, of, 'CD4+', 'T', cell, differentiation])]). relacion([sujeto(['Dissection', of, the, complement, system, gene, expression, identifies, 7, genes, specifically]), verbo([associated]), complemento([with, atopic, response, to, 'pollen,', including, 'C1QR1,', 'CFD,', 'CFP,', 'ITGB2,', 'ITGAX', and, confirms, the, role, of, 'C3AR1', and, 'C5AR1'])]). relacion([sujeto(['Two', of, these, genes, '(', 'ITGB2', and, 'C3AR1)', are, also, implicated, in, the, network, linking, complement, system, to, 'T', cell, 'activation,', which, comprises, 6, differentially]), verbo([expressed]), complemento([genes])]). relacion([sujeto(['C3AR1', is, also, significantly]), verbo([associated]), complemento([with, allergic, sensitisation, in, 'GWAS', data])]). relacion([sujeto(['Comparative', analyses, in, different, species, and, organ, systems]), verbo([have]), complemento([revealed, that, 'GRN', blueprints, are, composed, of, subcircuits, with, stereotypical, architectures, that, are, often, reused, as, modular, units])]). relacion([sujeto(['In', this, 'review,', we]), verbo([report]), complemento([the, evidence, for, the, 'GRN', underlying, renal, primordium, development])]). relacion([sujeto(['Definition', of, the, renal, field]), verbo([leads]), complemento([to, the, activation, of, a, core, regulatory, subcircuit, composed, of, the, transcription, factors, 'Pax2/8,', 'Gata3', and, 'Lim1'])]). relacion([sujeto(['These', transcription, factors, turn, on, a, second, layer, of, transcriptional, regulators, while, also]), verbo([activating]), complemento([effectors, of, tissue, morphogenesis, and, cellular, specialization])]). relacion([sujeto(['Evidence', shows, that, each, step, of, the, renal, primordium, developmental, program, is]), verbo([regulated]), complemento([by, structured, 'GRN', subunits, organized, in, a, hierarchical, manner])]). relacion([sujeto(['The', 'inositol-requiring', enzyme, 1, α, '(', 'IRE1α)', is, a, 'serine-threonine', kinase, that, plays, crucial, roles, in]), verbo([activating]), complemento([the, unfolded, protein, response])]). relacion([sujeto(['Studies']), verbo([suggest]), complemento([that, 'IRE1α', is, activated, during, thymic, 'T', cell, development, and, in, effector, 'CD8(+)', 'T', cells])]). relacion([sujeto(['However,', its, role, in]), verbo([regulating]), complemento(['T', helper, cell, differentiation, remains, unknown])]). relacion([sujeto(['We']), verbo([find]), complemento([that, 'IRE1α', is, 'up-regulated', and, activated, upon, 'CD4(+)', 'T', cell, activation, and, plays, an, important, role, in, promoting, cytokine, 'IL-4', production])]). relacion([sujeto(['CD4(+)', 'T', cells, from, 'IRE1α', 'KO', mice]), verbo([have]), complemento([reduced, 'IL-4', protein, 'expression,', and, this, impaired, 'IL-4', production, is, not, due, to, the, altered, expression, of, 'Th2', 'lineage-specific', transcription, 'factors,', such, as, 'GATA3'])]). relacion([sujeto(['Furthermore,', treatment, of, 'T', cells, with, an, 'IRE1α-specific', 'inhibitor,', 4, 'μ8C,']), verbo([leads]), complemento([to, a, block, in, 'IL-4,', 'IL-5,', and, 'IL-13', 'production,', confirming, the, role, of, 'IRE1α', in, the, regulation, of, 'IL-4'])]). relacion([sujeto(['However,', it, is, unclear, whether, or, not, vitamin, 'A', can]), verbo([regulate]), complemento(['Th1-Th2', balance, under, a, strong, 'Th1-polarizing', condition])]). relacion([sujeto(['Therefore,', the, purpose, of, our, study, was, to, examine, the, effect, of, vitamin, 'A', metabolite, 'all-trans', retinoic, acid, '(', 'ATRA)', on, 'Th1-Th2', differentiation, in, 'CD4+', 'T', cells, under, 'GATA-3', 'deficiency,', which, can]), verbo([induce]), complemento(['Th1-polarizing', condition])]). relacion([sujeto(['In', the, present, 'study,', 'GATA-3', deficiency, 'T', cells, were]), verbo([induced]), complemento([by, siRNA, and, checked, by, 'real-time', quantitative, 'PCR', and, western, blot])]). relacion([sujeto(['The', results, would, contribute, to, clarify, the, knowledge, of, the, role, of, vitamin, 'A', in]), verbo([regulating]), complemento(['Th1-Th2', balance, under, some, special, 'conditions,', and, help, to, explain, the, mechanism, of, immune, regulatory, function, of, vitamin, 'A'])]). relacion([sujeto(['T', cell, commitment, and, 'αβ/γδ', lineage, specification, in, the, thymus]), verbo([involves]), complemento([interactions, between, many, different, genes])]). relacion([sujeto(['Characterization', of, these, interactions, thus]), verbo([requires]), complemento([a, multiparameter, analysis, of, individual, thymocytes])]). relacion([sujeto(['We', show, that, during, 'T', cell, 'commitment,', 'Gata3']), verbo([has]), complemento([a, 'fundamental,', 'dose-dependent', role, in, maintaining, 'Notch1', 'expression,', with, thymocytes, becoming, 'T-cell-committed', when, they, 'co-express', 'Notch1,', 'Gata3', and, 'Bc11b'])]). relacion([sujeto(['The', existence, of, a, correlation, between, differentiation, potential, and, expression, of, the, 'pre-TCR', showed, that, 83, '%', of, 'αβ-committed', cells, do, not]), verbo([express]), complemento([the, 'pre-TCR', and, revealed, a, major, stochastic, component, in, 'αβ-lineage', specification])]). relacion([sujeto(['However,', indirect, evidence]), verbo([suggests]), complemento([they, may, produce, this, immunomodulatory, cytokine, in, the, steady, state])]). relacion([sujeto(['Through', intracellular, staining, for, transcription, 'factors,', we]), verbo([have]), complemento([defined, three, subsets, of, iNKT, cells, '(', 'NKT1,', 'NKT2', and, 'NKT17)', that, produced, distinct, 'cytokines;', these, represented, diverse, lineages, and, not, developmental, 'stages,', as, previously, thought])]). relacion([sujeto(['In', several, mouse, 'strains,', including, 'BALB/c,', 'NKT2', cells, were, abundant, and, were]), verbo([stimulated]), complemento([by, self, ligands, to, produce, 'IL-4'])]). relacion([sujeto(['In', those, 'strains,', 'steady-state', 'IL-4', conditioned, 'CD8(+)', 'T', cells, to, become, '\'', 'memory-like\',']), verbo([increased]), complemento([serum, concentrations, of, immunoglobulin, 'E', '(', 'IgE)', and, caused, dendritic, cells, to, produce, chemokines])]). relacion([sujeto(['We', identified, an, atypical, 'Luminal', 'A', subtype, characterized, by, high, genomic, 'instability,', 'TP53', 'mutations,', and]), verbo([increased]), complemento(['Aurora', kinase, 'signaling;', these, genomic, alterations, lead, to, a, worse, clinical, prognosis])]). relacion([sujeto(['Finally,', an, unbiased, pathway, analysis, revealed, multiple, 'rare,', but, mutually, 'exclusive,', alterations, linked, to]), verbo([loss]), complemento([of, activity, of, 'co-repressor', complexes, 'N-Cor', and, 'SMRT'])]). relacion([sujeto(['Our', work]), verbo([provides]), complemento([for, a, further, molecular, stratification, of, 'Luminal', 'A', breast, 'tumors,', with, potential, direct, clinical, implications])]). relacion([sujeto(['The', pathogenesis, of, experimental, cerebral, malaria, '(', 'ECM)', is, an, immunologic, 'process,']), verbo([mediated]), complemento([in, part, by, 'Th1', 'CD4(+)', 'T', cells])]). relacion([sujeto(['However,', the, role, of, the, 'Th1', 'CD4(+)', 'T', cell, differentiation, program, on, the, ability, to, control, parasitemia, and, susceptibility, to, 'ECM', disease, during, blood, stage, malaria]), verbo([has]), complemento([never, been, assessed, directly])]). relacion([sujeto(['Using', the, 'Plasmodium', berghei, 'ANKA', murine, model, of, 'ECM', and, mice, deficient, for, the, transcription, factor, 'T-bet', '(', the, master, regulator, of, 'Th1', 'cells)', on, the, susceptible, 'C57BL/6', 'background,', we, demonstrate, that, although, 'T-bet', plays, a, role, in, the, regulation, of, parasite, 'burden,', it, also]), verbo([promotes]), complemento([the, pathogenesis, of, 'ECM'])]). relacion([sujeto(['Resistance', to, 'ECM', in, 'Tbx21(-/-)', mice, was]), verbo([associated]), complemento([with, diminished, numbers, of, 'IFN-γ-producing', 'CD4(+)', 'T', cells, in, the, spleen, and, a, lower, accumulation, of, 'CD4(+)', and, 'CD8(+)', 'T', cells, in, the, brain])]). relacion([sujeto(['An', augmented, 'Th2', immune, response, characterized, by]), verbo([enhanced]), complemento([production, of, activated, 'GATA-3(+)', 'CD4(+)', 'T', cells, and, elevated, levels, of, the, 'eotaxin,', 'MCP-1,', and, 'G-CSF', cytokines, was, observed, in, the, absence, of, 'T-bet'])]). relacion([sujeto(['Our', results]), verbo([suggest]), complemento([that, in, virulent, 'malarias,', immune, modulation, or, therapy, resulting, in, an, early, shift, toward, a, 'Th2', response, may, help, to, ameliorate, the, most, severe, consequences, of, malaria, immunopathogenesis, and, the, prospect, of, host, survival])]). relacion([sujeto(['Prophylactic', vaccinations, are, generally, performed, to, protect, naïve, individuals, with, or, without]), verbo([suppressed]), complemento([immune, responsiveness])]). relacion([sujeto(['In', a, mouse, model, for, 'Influenza', vaccinations, the, specific, alterations, of, 'CD4(+)CD25(+)Foxp3(+)', regulatory, 'T-cells', '(', 'Tregs)', in, the, immune, modulation]), verbo([induced]), complemento([by, orally, supplied, oligosaccharides, containing, 'scGOS/lcFOS/pAOS', was, assessed])]). relacion([sujeto(['This', dietary, intervention]), verbo([increased]), complemento([vaccine, specific, 'DTH', responses])]). relacion([sujeto(['In', 'addition,', a, significant]), verbo([increased]), complemento([percentage, of, 'T-bet(+)', '(', 'Th1)', activated, 'CD69(+)CD4(+)', 'T', cells, '(', 'p<0'])]). relacion([sujeto([1, ')', and, reduced, percentage, of, 'Gata-3(+)', '(', 'Th2)']), verbo([activated]), complemento(['CD69(+)CD4(+)T', cells, '(', 'p<0'])]). relacion([sujeto(['Moreover,', although, no, absolute, difference, in, suppressive, capacity, could, be, 'detected,', an, alteration, in, cytokine, profile]), verbo([suggests]), complemento([a, regulatory, 'T', cell, shift, towards, a, reducing, 'Th1', suppression, 'profile,', supporting, an, improved, vaccination, response])]). relacion([sujeto(['The', modulation, of, 'Tregs', to, control, immune, responses]), verbo([provides]), complemento([an, additional, arm, of, intervention, using, alternative, strategies, possibly, leading, to, the, development, of, improved, vaccines])]). relacion([sujeto(['GATA']), verbo([binding]), complemento([protein, 3, '(', 'GATA3)', is, a, marker, of, urothelial, differentiation])]). relacion([sujeto(['GATA3,', 'p63,', and, 'PAX8']), verbo([nuclear]), complemento([expression, was, evaluated, using, standard, immunohistochemistry])]). relacion([sujeto(['We']), verbo([found]), complemento(['GATA3', positivity, in, 22, '(', 88, '%', ')', of, 25, 'UTUCs', and, 1, '(', 6, '%', ')', of, 18, 'CDCs'])]). relacion([sujeto(['We']), verbo([found]), complemento([p63, positivity, in, 23, '(', 92, '%', ')', of, 25, 'UTUCs', and, 2, '(', 11, '%', ')', of, 18, 'CDCs'])]). relacion([sujeto(['Immunohistochemical', expression, of, 'GATA3', was, higher, in, 'UTUC,']), verbo([suggesting]), complemento([a, potential, role, for, distinguishing, 'UTUC', from, 'CDC'])]). relacion([sujeto(['Adding', this, marker, to, the, combination, panel, of, p63, and, 'PAX8', might, improve, its, performance, in, the, diagnosis, of, epithelial, neoplasms]), verbo([involving]), complemento([the, renal, sinus])]). relacion([sujeto(['Bone', morphogenetic, proteins, '(', 'BMPs)', are, known, to]), verbo([induce]), complemento([diverse, differentiation, fates, in, human, embryonic, stem, cells, '(', 'hESCs)'])]). relacion([sujeto(['In', the, present, 'study,', we, compared, the, potency, at, which, 'BMP5,', 'BMP10', and, 'BMP13,', which, are, members, of, distinct, 'BMP', subgroups, due, to, differences, in, sequential, and, structural, 'homology,']), verbo([induce]), complemento([differentiation, in, hESCs, and, human, induced, pluripotent, stem, cells, '(', 'hiPSCs)'])]). relacion([sujeto(['We', 'observed,', in, agreement, with, previous, 'BMP4', model, 'studies,', that, all, ligands]), verbo([induced]), complemento([differentiation, to, the, trophoblast, lineage, in, the, absence, of, bFGF])]). relacion([sujeto(['However,', distinct, 'BMPs', exerted, differences, in, the, kinetics, of]), verbo([induced]), complemento(['differentiation,', with, 'BMP10', being, the, most, potent])]). relacion([sujeto([hiPSCs, and, hESCs, shared, comparable, expression, patterns, of, 'BMP', 'type-I', and, -, 'II', receptor, 'subtypes,', which, might, explain]), verbo([conserved]), complemento([properties, with, respect, to, ligand, potency, and, activation, of, 'SMAD-dependent', '(', via, 'SMAD1/5/8)', and, -, independent, '(', via, 'MAPK', 'p38)', signal, transduction, pathways])]). relacion([sujeto(['The', tested, 'BMPs', had, distinct, and, also]), verbo([conserved]), complemento([target, genes, such, as, 'CDX2,', 'DLX3,', 'DLX5,', 'GATA2,', 'GATA3,', 'HAND1,', 'ID2,', 'MSX2', and, 'TFAP2A,', known, to, be, associated, with, the, emergence, of, trophoblast, cells])]). relacion([sujeto([hESCs]), verbo([induced]), complemento([expression, of, the, 'BMP', antagonist, 'NOGGIN', as, a, protection, mechanism, to, constrict, extensive, 'BMP', action])]). relacion([sujeto(['Unlike', 'BMP4,', 'BMP10']), verbo([has]), complemento([been, shown, to, be, resistant, to, 'NOGGIN-induced', inhibition, which, in, part, might, explain, its, potency])]). relacion([sujeto(['Our', study]), verbo([has]), complemento([identified, 'BMP10,', a, 'cardiac-specific', 'protein,', as, a, superior, alternative, to, 'BMP4', for, inducing, trophoblast, differentiation, in, human, pluripotent, stem, cells])]). relacion([sujeto(['Apart', from, 'CASR,', the, genes]), verbo([associated]), complemento([with, serum, calcium, are, largely, unknown])]). relacion([sujeto(['We', conducted, a, 'genome-wide', association, 'meta-analysis', of, 39, ',', 400, individuals, from, 17, 'population-based', cohorts, and, investigated, the, 14, most, strongly]), verbo([associated]), complemento([loci, in, '≤', 21, ',', 679, additional, individuals])]). relacion([sujeto(['Rs1570669', near, 'CYP24A1', '(', 'P', =, 9.1e-12, ')', ',', rs10491003, upstream, of, 'GATA3', '(', 'P', =, 4.8e-9, ')', and, rs7481584, in, 'CARS', '(', 'P', =, 1.2e-10, ')', implicate, regions]), verbo([involved]), complemento([in, 'Mendelian', calcemic, 'disorders:', 'Rs1550532', in, 'DGKD', '(', 'P', =, 8.2e-11, ')', ',', also, associated, with, bone, 'density,', and, rs7336933, near, 'DGKH/KIAA0564', '(', 'P', =, 9.1e-10, ')', are, near, genes, that, encode, distinct, isoforms, of, diacylglycerol, kinase])]). relacion([sujeto(['Patients', suffering, from, cardiovascular, disease]), verbo([have]), complemento(['well-established', atherosclerotic, 'lesions,', rendering, lesion, regression, of, therapeutic, interest])]). relacion([sujeto(['The', 'OX40', '(', 'TNFRSF4)-OX40', ligand, '(', 'OX40L;', 'TNFSF4)', pathway, is, important, for, the, proliferation, and, survival, of, 'T', 'cells,']), verbo([stimulates]), complemento(['B', 'cells,', and, is, associated, with, cardiovascular, disease])]). relacion([sujeto(['We', hypothesized, that, interference, with, the, 'OX40-OX40L', 'pathway,', in, combination, with]), verbo([decreases]), complemento([in, 'cholesterol,', may, induce, regression, of, atherosclerosis])]). relacion([sujeto(['Interference', of, the, 'OX40-OX40L', pathway, reduced, 'Th2', 'responses,', as, shown, by]), verbo([decreases]), complemento([in, 'GATA-3', and, 'IL-4', levels])]). relacion([sujeto(['Notably,', 'IL-5', production, by, 'T', and, 'B1', cells, was, 'increased,', thus]), verbo([enhancing]), complemento([atheroprotective, oxidized, 'low-density', 'lipoprotein-specific', 'IgM', production])]). relacion([sujeto(['The']), verbo([increase]), complemento([in, 'IL-5', production, and, 'IgM', was, mediated, by, 'IL-33', production, by, 'APCs', upon, 'OX40L', blockade])]). relacion([sujeto(['We', conclude, that, interruption, of, the, 'OX40-OX40L', signaling, 'pathway,', combined, with]), verbo([decreases]), complemento([in, dietary, 'cholesterol,', induces, the, regression, of, atherosclerosis, through, induction, of, 'IL-5-producing', 'T', cells, and, oxidized, 'low-density', 'lipoprotein-specific', 'IgM', and, reductions, in, 'Th2', and, mast, cells])]). relacion([sujeto(['However,', no, prior, study]), verbo([has]), complemento([evaluated, the, expression, of, 'GATA-3', in, primary, bladder, adenocarcinoma])]). relacion([sujeto(['The', 'TMAs', were, subjected, to, immunohistochemical, analysis, for, 'GATA-3,', with]), verbo([nuclear]), complemento([labeling, scored, by, intensity, and, percentage, labeling])]). relacion([sujeto(['Diffuse']), verbo([nuclear]), complemento(['GATA-3', labeling, was, seen, in, 9, /, 22, '(', 41.0, '%', ')', 'SRCs', and, in, 2, /, 27, '(', 7.0, '%', ')', conventional, adenocarcinomas, '(', 'P=0'])]). relacion([sujeto(['No']), verbo([nuclear]), complemento(['GATA-3', labeling, was, seen, in, any, gastric, signet, ring, carcinoma])]). relacion([sujeto(['Diffuse,', moderate, to, strong]), verbo([nuclear]), complemento(['GATA-3', labeling, was, seen, in, 36, /, 36, '(', 100, '%', ')', primary, lobular, breast, carcinomas])]). relacion([sujeto(['We']), verbo([found]), complemento([that, in, a, fully, mismatched, heterotopic, mouse, heart, transplantation, 'model,', 'T', cells, deficient, for, 'T-bet', '(', prone, to, 'Th17', 'differentiation)', versus, 'RORγt', '(', prone, to, 'Th1', 'differentiation)', rejected, allografts, at, a, more, accelerated, 'rate,', indicating, a, predominance, of, 'Th17-', over, 'Th1-driven', alloimmunity])]). relacion([sujeto(['Importantly,', 'T', cells, doubly, deficient, for, both, 'T-bet', and, 'RORγt', differentiated, into, alloreactive, 'GATA-3-expressing', 'Th2', 'cells,', which, promptly]), verbo([induced]), complemento([allograft, rejection, characterized, by, a, 'Th2-type', intragraft, expression, profile, and, eosinophilic, infiltration])]). relacion([sujeto(['We', summarize, 'that,', whereas, 'Th17', cells, predictably]), verbo([promote]), complemento([allograft, 'rejection,', 'IL-4-producing', 'GATA-3(+)', 'Th2', 'cells,', which, are, generally, thought, to, protect, allogeneic, 'transplants,', may, actually, be, potent, facilitators, of, organ, transplant, rejection, in, the, absence, of, 'T-bet', and, 'RORγt'])]). relacion([sujeto(['Although', intergenic, long, noncoding, 'RNAs', '(', 'lincRNAs)']), verbo([have]), complemento([been, linked, to, gene, regulation, in, various, 'tissues,', little, is, known, about, lincRNA, transcriptomes, in, the, 'T', cell, lineages])]). relacion([sujeto(['Many', were]), verbo([bound]), complemento([and, regulated, by, the, key, transcription, factors, 'T-bet,', 'GATA-3,', 'STAT4', and, 'STAT6'])]). relacion([sujeto(['We']), verbo([found]), complemento([that, the, lincRNA, 'LincR-Ccr2-5\'AS,', together, with, 'GATA-3,', was, an, essential, component, of, a, regulatory, circuit, in, gene, expression, specific, to, the, 'TH2', subset, of, helper, 'T', cells, and, was, important, for, the, migration, of, 'TH2', cells])]). relacion([sujeto(['A', total, of, 38, patients, met, inclusion, criteria, '(', 20, patients, who]), verbo([responded]), complemento([and, 18, patients, who, did, not, 'respond)'])]). relacion([sujeto(['If', a, patient]), verbo([has]), complemento([a, preexisting, 'Th1', immunologic, response, within, the, 'tumor,', there, is, no, value, in, using, a, therapy, intended, to, create, a, 'Th1', immunologic, response])]). relacion([sujeto(['An', algorithm, integrating, 3, 'IHC', methods]), verbo([provided]), complemento([a, sensitive, and, specific, technique, that, may, become, a, useful, tool, for, pathologists, and, urologists, to, predict, response, to, 'BCG', in, patients, with, carcinoma, in, situ, of, the, bladder])]). relacion([sujeto(['The', fibroblast, growth, factor, receptor, 2, '(', 'FGFR2)', locus]), verbo([has]), complemento([been, consistently, identified, as, a, breast, cancer, risk, locus, in, independent, 'genome-wide', association, studies])]). relacion([sujeto(['Using', a, network, derived, from, 2, ',', 0, transcriptional, profiles, we, identify, 'SPDEF,', 'ERα,', 'FOXA1,', 'GATA3', and, 'PTTG1', as, master, regulators, of, fibroblast, growth, factor, receptor, 2, 'signalling,', and, show, that, 'ERα', occupancy]), verbo([responds]), complemento([to, fibroblast, growth, factor, receptor, 2, signalling])]). relacion([sujeto(['Our', results, indicate, that, 'ERα,', 'FOXA1', and, 'GATA3', contribute, to, the, regulation, of, breast, cancer, susceptibility, 'genes,', which, is, consistent, with, the, effects, of, 'anti-oestrogen', treatment, in, breast, cancer, 'prevention,', and]), verbo([suggest]), complemento([that, fibroblast, growth, factor, receptor, 2, signalling, has, an, important, role, in, mediating, breast, cancer, risk])]). relacion([sujeto(['Innate', lymphocyte, populations, play, a, central, role, in]), verbo([conferring]), complemento([protective, immunity, at, the, mucosal, frontier])]). relacion([sujeto(['In', this, 'study,', we, demonstrate, that, 'T', cell, factor, 1, '(', 'TCF-1;', encoded, by, 'Tcf7),', a, transcription, factor, also, important, for, 'NK', and, 'T', cell, 'differentiation,', is]), verbo([expressed]), complemento([by, multiple, innate, lymphoid, cell, '(', 'ILC)', 'subsets,', including, 'GATA3(+)', nuocytes, '(', 'ILC2)', and, 'NKp46(+)', 'ILCs', '(', 'ILC3),', which, confer, protection, against, lung, and, intestinal, inflammation])]). relacion([sujeto(['TCF-1', was, intrinsically]), verbo([required]), complemento([for, the, differentiation, of, both, 'ILC2', and, 'NKp46(+)', 'ILC3'])]). relacion([sujeto(['Furthermore,', a, reduction, in, 'T-bet', expression]), verbo([required]), complemento([for, 'Notch-2-dependent', development, of, 'NKp46(+)', 'ILC3', showed, a, 'dose-dependent', reduction, in, 'TCF-1', expression])]). relacion([sujeto(['Collectively,', our, findings, demonstrate, an, essential, requirement, for, 'TCF-1', in, 'ILC2', differentiation, and]), verbo([reveal]), complemento([a, link, among, 'Tcf7,', 'Notch,', and, 'Tbx21', in, 'NKp46(+)', 'ILC3', development])]). relacion([sujeto(['Dendritic', cells, '(', 'DCs)', are, the, central, architects, of, the, immune, 'response,']), verbo([inducing]), complemento([inflammatory, or, tolerogenic, 'immunity,', dependent, on, their, activation, status])]). relacion([sujeto(['As', 'such,', 'DCs', are, highly, attractive, therapeutic]), verbo([targets]), complemento([and, may, hold, the, potential, to, control, detrimental, immune, responses])]). relacion([sujeto(['TIM-4,']), verbo([expressed]), complemento([on, 'APCs,', has, complex, functions, in, 'vivo,', acting, both, as, a, costimulatory, molecule, and, a, phosphatidylserine, receptor])]). relacion([sujeto(['In', this, 'study,', we, demonstrate, that, 'Ab', blockade, of, 'DC-expressed', 'TIM-4']), verbo([leads]), complemento([to, increased, induction, of, induced, regulatory, 'T', cells, '(', 'iTregs)', from, naive, 'CD4(+)', 'T', 'cells,', both, in, vitro, and, in, vivo])]). relacion([sujeto(['In', 'addition,', blockade, of, 'TIM-4', on, previously]), verbo([activated]), complemento(['DCs', still, leads, to, increased, iTreg, induction])]). relacion([sujeto([iTregs]), verbo([induced]), complemento([under, 'TIM-4', blockade, have, equivalent, potency, to, control, 'and,', upon, adoptive, 'transfer,', significantly, prolong, skin, allograft, survival, in, vivo])]). relacion([sujeto(['In', 'RAG(-/-)', recipients, of, skin, allografts, adoptively, transferred, with, 'CD4(+)', 'T', 'cells,', we, show, that, 'TIM-4', blockade, in, vivo, is]), verbo([associated]), complemento([with, a, 3, -, fold, prolongation, in, allograft, survival])]). relacion([sujeto(['Furthermore,', in, this, mouse, model, of, skin, 'transplantation,']), verbo([increased]), complemento([induction, of, allospecific, iTregs, and, a, reduction, in, 'T', effector, responses, were, 'observed,', with, decreased, 'Th1', and, 'Th2', responses])]). relacion([sujeto(['This']), verbo([enhanced]), complemento([allograft, survival, and, protolerogenic, skewing, of, the, alloresponse, is, critically, dependent, on, conversion, of, naive, 'CD4(+)', to, 'Tregs', in, vivo])]). relacion([sujeto(['Collectively,', these, studies, identify, blockade, of, 'DC-expressed', 'TIM-4', as, a, novel, strategy, that, holds, the, capacity, to]), verbo([induce]), complemento([regulatory, immunity, in, vivo])]). relacion([sujeto(['Probiotics', are, believed, to]), verbo([have]), complemento([interaction, with, immune, cells, through, sustained, effects, on, gene, expression, of, different, cytokines, and, transcription, factors])]). relacion([sujeto(['The', present, randomized, 'doubled-blind', controlled, clinical, trial, was, performed]), verbo([recruiting]), complemento([75, individuals, with, 'BMI', 25, -, 35, ',', who, were, randomly, assigned, to, the, following, three, 'groups:', 'Group', 1, '(', n, =, 25, ')', who, consumed, regular, yogurt, as, part, of, a, low, calorie, diet, '[', 'RLCD],', group, 2, '(', n, =, 25, ')', who, received, probiotic, yogurt, with, a, 'LCD', '[', 'PLCD]', and, group, 3, '(', n, =, 25, ')', who, consumed, probiotic, yogurt, without, 'LCD', '[', 'PWLCD]', for, 8, week])]). relacion([sujeto(['In', three, 'groups,', 'ROR-γt', expression, was, reduced, '(', 'P', =, 0.007, ')', and, 'FOXP3', was]), verbo([increased]), complemento(['(', 'P', &, 'lt;', 0.001, ')'])]). relacion([sujeto(['Interestingly,', the, expression, of, 'T-bet', 'gene,', which, was, significantly]), verbo([decreased]), complemento([in, 'PLCD', and, 'PWLCD', groups, '(', 'P', &, 'lt;', 0.001, ')', ',', whereas, gene, expression, of, 'IFN-γ', decreased, in, all, three, groups])]). relacion([sujeto(['Our', results]), verbo([suggest]), complemento([that, weight, loss, diet, and, probiotic, yogurt, had, synergistic, effects, on, 'T-cell', subset, specific, gene, expression, in, peripheral, blood, mononuclear, cells, among, overweight, and, obese, individuals])]). relacion([sujeto(['Asthmatic', inflammation, is]), verbo([mediated]), complemento([by, a, type, 2, helper, 'T', cell, '(', 'Th2)', cytokine, 'response,', and, blocking, 'Th2', cytokine, production, is, proven, to, have, a, potent, therapeutic, effect, against, asthmatic, inflammation])]). relacion([sujeto(['Using', 'IL-4-green', fluorescent, protein, '(', 'GFP)', reporter, 'mice,', we, demonstrated, that, 'Bavachinin,', a, single, compound, isolated, from, a, 'Chinese', 'herb,', significantly]), verbo([inhibited]), complemento(['Th2', cytokine, 'production,', including, 'IL-4,', 'IL-5', and, 'IL-13'])]). relacion([sujeto(['While', most, factors, used, as, reprogramming, transgenes, can, be, replaced, by, other, 'means,', 'Oct4']), verbo([has]), complemento([remained, essential, until, now])]). relacion([sujeto(['Three', recent, papers]), verbo([have]), complemento([now, broken, this, barrier, through, the, use, of, opposing, lineage, specifying, transgenes, and, chemical, 'modulation,', thus, signifying, a, milestone, in, advancing, our, understanding, of, pluripotency, induction])]). relacion([sujeto(['Endothelial', microparticles, '(', 'EMPs)', can, be]), verbo([involved]), complemento([in, inflammatory, 'process,', blood, 'coagulation,', and, regulation, of, vascular, function])]). relacion([sujeto(['However,', it, remains, unclear, whether, 'EMPs']), verbo([participate]), complemento([in, the, pathogenesis, of, 'ACS'])]). relacion([sujeto(['Twenty', hospitalized, patients, with, normal, coronary, angiography, were]), verbo([recruited]), complemento([as, controls])]). relacion([sujeto(['This', study, proved, that, the, frequency, of, 'EMPs', was, significantly]), verbo([increased]), complemento([in, 'ACS', patients])]). relacion([sujeto(['EMPs', could, significantly, upregulate, the, differentiation, and, function, of, 'Th1', through]), verbo([increasing]), complemento([the, expression, of, 'T-bet', mRNA, and, protein])]). relacion([sujeto(['Furthermore,', this, study, also, indicated, that, 'EMP', treatment, in, vitro, could]), verbo([promote]), complemento([the, expression, of, 'TNF-α,', which, exerts, adverse, effects, on, the, pathogenesis, and, progression, of, atherosclerosis])]). relacion([sujeto(['EMPs', may, be]), verbo([involved]), complemento([in, the, immune, and, inflammatory, processes, that, take, part, in, artery, atherosclerosis, and, that, they, do, so, by, regulating, 'Th1/Th2', differentiation, and, function])]). relacion([sujeto(['Compared', with, the, control, 'group,', in, injury, and, 'LPS', treatment, 'groups,', the, level, of, 'IFN-γ', '(', as, a, 'Th1']), verbo([associated]), complemento(['cytokine)', in, brain, tissue, significantly, increased, '(', 'P<0'])]). relacion([sujeto(['The', expressions, of, 'Th1']), verbo([associated]), complemento(['cytokines,', especially, soluble, cytokine, 'IFN-γ,', increased, in, brain, and, spinal, cord, injury])]). relacion([sujeto(['Systemic', inhibition, of, the, inflammatory, enzyme, cyclooxygenase, '(', 'COX)', 2]), verbo([decreases]), complemento([the, risk, of, breast, cancer, and, its, recurrence])]). relacion([sujeto(['COX-2(MEC)KO', tumors, showed]), verbo([decreased]), complemento([expression, of, 'Ki67,', a, proliferation, 'marker,', as, well, as, reduced, 'VEGFA,', its, receptor, 'VEGFR2,', endothelial, 'NOS', and, the, vascular, endothelial, marker, 'CD31,', indicating, reduced, tumor, vascularization])]). relacion([sujeto(['COX-2(MEC)KO', tumors, contained, more, 'CD4+', 'T', helper, '(', 'Th)', cells, and, 'CD8+', cytotoxic, immune, cells, '(', 'CTL)', consistent, with]), verbo([increased]), complemento([immune, surveillance])]). relacion([sujeto(['The', ratio, of, 'Th', markers, 'Tbet', '(', 'Th1)', to, 'GATA3', '(', 'Th2)', was, 'higher,', and, levels, of, 'Retnla,', a, 'M2', macrophage, 'marker,', 'lower,', in, 'COX-2(MEC)KO', tumor, infiltrating, leukocytes, compared, to, 'WT,']), verbo([suggesting]), complemento([a, prevalence, of, 'pro-immune', 'Th1', over, immune, suppressive, 'Th2', 'lymphocytes,', and, reduced, macrophage, polarization, to, the, immune, suppressive, 'M2', phenotype])]). relacion([sujeto(['Enhanced', immune, surveillance, in, 'COX-2(MEC)KO', tumors, was, coincident, with]), verbo([increased]), complemento([intratumoral, 'CXCL9,', a, 'T', cell, 'chemoattractant,', and, decreased, expression, of, 'T', lymphocyte, 'co-inhibitory', receptors, 'CTLA4', and, 'PD-1,', as, well, as, 'PD-L1,', the, ligand, for, 'PD-1'])]). relacion([sujeto(['PD-L1', was, also]), verbo([decreased]), complemento([in, 'IFNγ-treated', 'COX-2KD', mouse, mammary, cancer, cells, in, vitro, 'and,', compared, to, control, 'cells,', growth, of, 'COX-2KD', cells, as, orthotopic, tumors, in, immune, competent, mice, was, markedly, suppressed])]). relacion([sujeto(['The', data, strongly, support, 'that,', in, addition, to, its, angiogenic, 'function,', tumor, cell, 'COX-2']), verbo([suppresses]), complemento([intratumoral, cytotoxic, 'CD8+', immune, cell, 'function,', possibly, through, upregulation, of, immune, 'checkpoints,', thereby, contributing, to, tumor, immune, escape])]). relacion([sujeto(['CHL-derived', 'TH', cells]), verbo([express]), complemento(['TH1-associated', 'CXCR3/CCR5', and, 'TNFα/IFNγ/interleukin-2', '(', 'IL-2)', and, less, 'TH2-associated', 'CCR3/CCR4,', with, no, 'IL-4/IL-13'])]). relacion([sujeto(['We', confirmed, and, extended, these, studies, using, tissue, microarray, immunohistochemistry, '(', 'TMA-IHC)', from, a, large, 'CHL', tissue, bank, '(', n, =, 122, ')', and, demonstrate, 'TH1-associated', 'TBET', is, abundant, in, 'CHL,', and, 'TH2-associated', 'CMAF/GATA3', and, 'exhaustion-associated', 'PD1']), verbo([expressed]), complemento([at, significantly, lower, levels])]). relacion([sujeto(['These', molecular, insights, into, the, 'CHL-associated', 'TH', offer, potential, 'diagnostic,', prognostic, and, pharmacologically, modifiable, therapeutic]), verbo([targets]), complemento([and, do, not, support, the, established, view, of, a, 'TH2-enriched,', 'senescent/exhausted,', 'hypofunctional,', hypoproliferative, infiltrate])]). relacion([sujeto(['Recently,', these, cells]), verbo([have]), complemento([also, emerged, as, key, players, in, the, development, of, allergic, inflammation, at, multiple, barrier, surfaces])]). relacion([sujeto(['The', epithelial, 'cell-derived', cytokines, 'IL-25,', 'IL-33,', and, 'TSLP']), verbo([regulate]), complemento([the, activation, and, effector, functions, of, 'ILC2s,', and, recent, studies, suggest, that, their, responsiveness, to, these, cytokines, and, other, factors, may, depend, on, their, tissue, environment])]). relacion([sujeto(['In', this, 'review,', we, focus, on, recent, advances, in, our, understanding, of, how, 'ILC2s', are, differentially]), verbo([regulated]), complemento([in, the, context, of, allergic, inflammation, and, discuss, the, therapeutic, potential, of, targeting, 'ILC2s', in, the, treatment, of, allergic, diseases])]). relacion([sujeto(['Of', the, three, cases, without, 'nephrectomy,', no, tumor, in, the, renal, pelvis, could, be, visualized, with, 'endoscopy,', however, one, case, was]), verbo([associated]), complemento([with, 'UC', of, the, urinary, bladder])]). relacion([sujeto(['Unlike', 'CDC', and, 'non-calyceal', 'UC,', 'RCXC', shows, predominantly, urothelial, and, squamous, differentiation, and, is]), verbo([associated]), complemento([with, an, in, situ, component, of, adjacent, renal, calyces])]). relacion([sujeto(['By', 'IHC,', 'RCXC', exhibited, features, intermediate, between, 'UC', and, 'CDC', with]), verbo([decreased]), complemento([or, negative, immunoreactivity, for, 'PAX8', and, 'GATA'])]). relacion([sujeto(['GATA-3', and, estrogen, receptor, '(', 'ER)', are]), verbo([involved]), complemento([in, a, positive, 'cross-regulatory', loop, and, are, frequently, coexpressed, in, breast, cancers])]). relacion([sujeto(['Recent', 'genome-wide', association, studies, '(', 'GWAS)']), verbo([have]), complemento([provided, the, first, unambiguous, evidence, for, common, inherited, susceptibility, to, 'BCP-ALL,', identifying, susceptibility, loci, at, 7, p12])]). relacion([sujeto(['The', rs10828317, association, was, shown, to, be, specifically]), verbo([associated]), complemento([with, hyperdiploid, 'ALL,', whereas, the, 'rs3824662-associated', risk, was, confined, to, nonhyperdiploid, 'non-TEL-AML1', +, 'ALL'])]). relacion([sujeto(['These', findings]), verbo([provide]), complemento([further, insights, into, the, genetic, and, biological, basis, of, inherited, genetic, susceptibility, to, 'BCP-ALL', and, the, influence, of, constitutional, genotype, on, disease, development])]). relacion([sujeto(['A', 'Th1', polarization, of, the, immune, 'response,', 'up-regulation', of, 'Th17', cells, and]), verbo([decreased]), complemento([number, of, 'Treg', cells, have, been, demonstrated, in, 'ITP', patients])]). relacion([sujeto(['We']), verbo([found]), complemento([that, dexamethasone, returned, the, ratio, of, 'Th1/Th2', and, the, number, of, 'Th17', and, 'Treg', cells, to, the, normal, levels])]). relacion([sujeto(['Furthermore,', we, identified, that, dexamethasone, corrected, the, 'T', cell, subset, levels, through]), verbo([inhibiting]), complemento(['GATA3', and, 'FOXp3', expression, and, promoting, 'RORγt', expression])]). relacion([sujeto(['Taken', 'together,', we]), verbo([reported]), complemento([a, previously, unrecognized, mechanism, on, dexamethasone, in, the, 'ITP', treatment])]). relacion([sujeto(['CD226', costimulatory, signals, strongly]), verbo([promote]), complemento(['Th1', 'differentiation,', enhancing, 'IFN-γ', production, by, naive, 'T', cells])]). relacion([sujeto(['We', recently]), verbo([reported]), complemento([that, knockdown, of, 'CD226', on, human, 'T', cells, resulted, in, a, decrease, in, 'T-bet', and, 'IFN-γ', expression])]). relacion([sujeto(['In', this, 'study,', we]), verbo([found]), complemento([that, 'CD226', and, its, ligand, 'CD155', were, decreased, on, 'Th2-polarized', naive, 'T', 'cells,', whereas, both, were, highly, expressed, under, 'Th17', conditions])]). relacion([sujeto(['Most', 'IFN-γ-', and, 'IL-17-producing', cells]), verbo([expressed]), complemento([high, levels, of, 'CD226,', but, production, of, 'IL-13', did, not, correlate, with, 'CD226', expression])]). relacion([sujeto(['CD226', knockdown, by, lentiviral, transduction, resulted, in]), verbo([increased]), complemento(['STAT-6', 'phosphorylation,', enhanced, 'GATA3', 'expression,', and, consequently, higher, production, of, 'IL-4', and, 'IL-13'])]). relacion([sujeto(['Under', 'Th17', 'conditions,', 'CD226-depleted', cells, showed, slightly, impaired, 'IL-17', 'secretion,']), verbo([suggesting]), complemento([that, 'CD226', 'contributes,', in, 'part,', to, 'IL-17', production, but, is, dispensable, for, 'Th17', cell, generation])]). relacion([sujeto(['In', line, with, these, 'results,', 'CD226', blockade, with, neutralizing, 'Abs', efficiently]), verbo([inhibited]), complemento(['T', cell, activation, and, proliferation, and, production, of, 'IFN-γ', and, 'IL-17,', whereas, 'IL-13', secretion, remained, functional])]). relacion([sujeto(['Taken', 'together,', our, results, establish, an, important, role, for, 'CD226', in, differentially]), verbo([regulating]), complemento([the, proinflammatory, '(', 'Th1/Th17)/anti-inflammatory', '(', 'Th2)', 'balance,', suggesting, that, the, 'CD226/CD155', interaction, could, potentially, be, targeted, in, therapeutic, approaches, to, human, autoimmune, diseases])]). relacion([sujeto(['The', hybrid, 'Th1/2', phenotype, is, stably]), verbo([maintained]), complemento([in, memory, cells, in, vivo, for, months])]). relacion([sujeto(['It', resists, reprogramming, into, classic, 'Th1', or, 'Th2', cells, by, 'Th1-', or, 'Th2-promoting', 'stimuli,', which, rather]), verbo([induce]), complemento([quantitative, modulations, of, the, combined, 'Th1', and, 'Th2', programs, without, abolishing, either])]). relacion([sujeto(['The', hybrid, phenotype, is]), verbo([associated]), complemento([with, intermediate, manifestations, of, both, 'Th1', and, 'Th2', cell, properties])]). relacion([sujeto(['Consistently,', hybrid, 'Th1/2', cells, support, inflammatory, 'type-1', and, 'type-2', immune, responses, but]), verbo([cause]), complemento([less, immunopathology, than, 'Th1', and, 'Th2', 'cells,', respectively])]). relacion([sujeto(['Thus,', we, propose, the, 'self-limitation', of, effector, 'T', cells, based, on, the, stable, 'cell-intrinsic', balance, of, two, opposing, differentiation, programs, as, a, novel, concept, of, how, the, immune, system, can]), verbo([prevent]), complemento([excessive, inflammation])]). relacion([sujeto(['Each', of, the, two, distinct, &, 'quot;master', 'regulators"']), verbo([promotes]), complemento([differentiation, of, its, respective, sister, lineage])]). relacion([sujeto(['But', they, also]), verbo([suppress]), complemento([one, 'other,', leading, to, their, mutually, exclusive, expression, in, the, two, ensuing, lineages])]). relacion([sujeto(['This', antagonism]), verbo([ensures]), complemento([robust, polarization, into, two, discretely, distinct, cell, types])]). relacion([sujeto(['These', hybrid, cells, are, functionally, active, and, possess, the, benefit, of, 'moderation:', 'self-limitation', of, effector, 'T', cell, function, to]), verbo([prevent]), complemento([excessive, 'inflammation,', a, permanent, risk, in, host, defense, that, can, cause, tissue, damage, or, autoimmunity])]). relacion([sujeto(['Gene', regulatory, network, analysis]), verbo([suggests]), complemento([that, stabilization, of, the, intermediate, center, in, a, polarizing, system, can, be, achieved, by, minor, tweaking, of, the, architecture, of, the, mutual, suppression, gene, 'circuit,', and, thus, is, a, design, option, readily, available, to, evolution])]). relacion([sujeto(['The', transcription, factor, 'GATA-3', is]), verbo([expressed]), complemento([and, required, for, differentiation, and, function, throughout, the, 'T', lymphocyte, lineage])]). relacion([sujeto(['Despite', evidence, it, may, also, be]), verbo([expressed]), complemento([in, multipotent, hematopoietic, stem, cells, '(', 'HSCs),', any, role, for, 'GATA-3', in, these, cells, has, remained, unclear])]). relacion([sujeto(['Here', we]), verbo([found]), complemento(['GATA-3', was, in, the, cytoplasm, in, quiescent, 'long-term', stem, cells, from, 'steady-state', bone, marrow, but, relocated, to, the, nucleus, when, 'HSCs', cycled])]). relacion([sujeto(['Relocation', depended, on, signaling, via, the, 'mitogen-activated', protein, kinase, p38, and, was]), verbo([associated]), complemento([with, a, diminished, capacity, for, 'long-term', reconstitution, after, transfer, into, irradiated, mice])]). relacion([sujeto(['Deletion', of, 'Gata3']), verbo([enhanced]), complemento([the, repopulating, capacity, and, augmented, the, 'self-renewal', of, 'long-term', 'HSCs', in, 'cell-autonomous', fashion, without, affecting, the, cell, cycle])]). relacion([sujeto(['Our', observations, position, 'GATA-3', as, a, regulator, of, the, balance, between, 'self-renewal', and, differentiation, in, 'HSCs', that]), verbo([acts]), complemento([downstream, of, the, p38, signaling, pathway])]). relacion([sujeto(['Th2', cells, are, crucially, important, in, allergic, disease, and, the, possible, involvement, of, 'Treg', and, 'Th17', cells]), verbo([has]), complemento([not, been, clearly, identified])]). relacion([sujeto(['To', identify, the, mRNA, expression, of, 'T', cell, transcription, factors, in, nasal, mucosa, in, patients, with, allergic, rhinitis, '(', 'AR)', and, to]), verbo([reveal]), complemento([their, correlations, with, clinical, features])]). relacion([sujeto(['GATA3', and, 'RORC', were, significantly]), verbo([increased]), complemento([and, 'Foxp3', was, significantly, decreased, in, the, 'AR', group])]). relacion([sujeto(['Moderate-to-severe', 'AR', group, also, had]), verbo([increased]), complemento([expression, of, 'GATA3', and, 'RORC', than, mild, 'AR', 'group,', suggesting, severity, of, 'AR', influence, expression, of, transcription, factors])]). relacion([sujeto(['Correlation', analysis, showed, that, none, of, these, transcription, factors, were]), verbo([associated]), complemento([with, severity, of, clinical, 'symptoms,', eosinophil, counts, and, skin, prick, test, severity, and, that, 'IgE', level, was, significantly, correlated, with, expression, level, of, 'GATA3', and, 'RORC,', suggesting, an, association, of, 'IgE', production, with, 'Th2', and, 'Th17', cells])]). relacion([sujeto(['Increased', mRNA, expression, of, 'GATA3', '(', 'Th2),']), verbo([increased]), complemento([expression, of, 'RORC', and, decreased, expression, of, 'Foxp3', may, be, important, in, pathogenesis, of, 'AR'])]). relacion([sujeto(['Infections', with, the, parasitic, flagellate, 'Ichthyobodo', necator, '(', 'Henneguy,', 1883, ')']), verbo([cause]), complemento([severe, skin, and, gill, disease, in, rainbow, trout, 'Oncorhynchus', mykiss, '(', 'Walbaum,', 1792, ')', juveniles])]). relacion([sujeto(['The', epidermal, disturbances, including, hyperplasia, and, mucous, cell, exhaustion]), verbo([caused]), complemento([by, parasitization, are, 'known,', but, no, details, on, specific, cellular, and, humoral, reactions, have, been, presented])]). relacion([sujeto([&, 'nbsp;necator', was, established, in, the, laboratory, and, used, to]), verbo([induce]), complemento([an, experimental, infection, of, juvenile, rainbow, trout])]). relacion([sujeto(['IHC', showed, a, significant]), verbo([increase]), complemento([in, the, occurrence, of, 'IgM-positive', cells, in, the, skin, of, the, infected, 'fish,', whereas, 'IgT-positive', cells, were, eliminated, and, the, number, of, 'CD8-positive', cells, declined])]). relacion([sujeto([qPCR, studies, supported, the, 'IHC', findings, showing, a, significant]), verbo([increase]), complemento([in, 'IgM', and, a, decrease, in, the, 'CD8', gene, expression])]). relacion([sujeto(['Expression', of, cytokines, '(', 'IL-1β,', 'IL-4/13A,', 'IL-6,', 'IL-8,', 'IL-10),', the, cell, marker, 'CD4', and, the, transcription, factor, 'GATA3', showed, a, significant]), verbo([increase]), complemento([after, infection])]). relacion([sujeto(['Cytokine', profiling, including, 'up-regulation', of, 'IL-4/13A', and, 'IL-10', genes, and, transcription, factor, 'GATA3', connected, to, the, proliferation, of, 'IgM', producing, lymphocytes]), verbo([suggests]), complemento([a, partial, shift, towards, a, 'Th2', response, associated, with, the, 'I'])]). relacion([sujeto(['IL-19', is, not, detected, in, normal, artery, and, is]), verbo([expressed]), complemento([to, a, greater, degree, in, plaque, from, symptomatic, versus, asymptomatic, 'patients,', suggesting, a, compensatory, 'counter-regulatory', function])]). relacion([sujeto(['Gene', expression, in, splenocytes, from, 'IL-19-treated', mice, demonstrated, immune, cell, 'Th2', 'polarization,', with]), verbo([decreased]), complemento([expression, of, 'T-bet,', 'interferon-γ,', 'interleukin-1β,', and, 'interleukin-12β', and, increased, expression, of, 'GATA3', and, 'FoxP3', mRNA])]). relacion([sujeto(['Cellular', characterization, of, plaque, by, immunohistochemistry, demonstrated, that, 'IL-19-treated', mice]), verbo([have]), complemento([significantly, less, macrophage, infiltrate, compared, with, controls, '(', 'P<0'])]). relacion([sujeto(['Treatment', of, cultured, endothelial, 'cells,', vascular, smooth, muscle, 'cells,', and, bone, 'marrow-derived', macrophages, with, 'IL-19', resulted, in, a, significant]), verbo([decrease]), complemento([in, chemokine, mRNA, and, mRNA, stability, protein, human, antigen, 'R'])]). relacion([sujeto(['These', data]), verbo([suggest]), complemento([that, 'IL-19', is, a, potent, inhibitor, of, experimental, 'atherosclerosis,', with, diverse, mechanisms, including, immune, cell, 'polarization,', decrease, in, macrophage, 'adhesion,', and, decrease, in, gene, expression])]). relacion([sujeto(['Individual', genetic, variations, may]), verbo([have]), complemento([a, significant, influence, on, the, survival, of, metastatic, prostate, cancer, '(', 'PCa)', patients])]). relacion([sujeto(['We', aimed, to, identify]), verbo([target]), complemento([genes, and, their, variations, involved, in, the, survival, of, 'PCa', patients, using, a, single, nucleotide, polymorphism, '(', 'SNP)', panel])]). relacion([sujeto(['SNPs']), verbo([associated]), complemento([with, survival, were, screened, by, a, 'log-rank', test])]). relacion([sujeto(['Fourteen', 'SNPs', in, 6, 'genes,', 'XRCC4,', 'PMS1,', 'GATA3,', 'IL13,', 'CASP8,', and, 'IGF1,', were, identified, to]), verbo([have]), complemento([a, statistically, significant, association, with, 'cancer-specific', survival])]). relacion([sujeto(['The', 'high-risk', group, was, independently]), verbo([associated]), complemento([with, survival, in, a, multivariate, analysis, that, included, conventional, clinicopathological, variables, '(', 'P', =, 0.006, ')'])]). relacion([sujeto(['We', identified, 14, candidate, 'SNPs', in, 6, 'cancer-related', 'genes,', which, were]), verbo([associated]), complemento([with, poor, survival, in, patients, with, metastatic, 'PCa'])]). relacion([sujeto(['GATA3', is, a, member, of, a, group, of, 'zinc-finger', transcription, factors, that, is]), verbo([involved]), complemento([in, cell, development, and, differentiation])]). relacion([sujeto(['Recent', studies]), verbo([have]), complemento([shown, 'that,', among, 'tumors,', 'GATA3', is, commonly, expressed, in, both, urothelial, tumors, and, breast, epithelial, neoplasms])]). relacion([sujeto(['With', the, exception, of, salivary, gland, and, parathyroid, 'tumors,', 'GATA3']), verbo([has]), complemento([been, reported, to, be, either, absent, or, only, rarely, expressed, in, other, epithelial, tumors])]). relacion([sujeto(['Owing', to, its, restricted, expression, in, urothelial, and, breast, 'carcinomas,', 'GATA3']), verbo([has]), complemento([proved, to, be, a, useful, immunohistochemical, marker, for, assisting, in, distinguishing, these, 2, groups, of, neoplasms, from, other, malignancies, with, which, they, may, be, confused])]). relacion([sujeto(['We']), verbo([find]), complemento([a, continuum, of, mixed, phenotypes, in, which, individual, cells, 'co-express', the, two, 'lineage-specific', master, regulators, at, levels, that, gradually, depend, on, levels, of, the, two, input, signals])]). relacion([sujeto(['Using', mathematical, modeling, we, show, that, such, tunable, mixed, phenotype, arises, if, autoregulatory, positive, feedback, loops, in, the, gene, network]), verbo([regulating]), complemento([this, process, are, gradual, and, dominant, over, 'cross-pathway', inhibition])]). relacion([sujeto(['We', also]), verbo([find]), complemento([that, expression, of, the, 'lineage-specific', cytokines, follows, two, independent, stochastic, processes, that, are, biased, by, expression, levels, of, the, master, regulators])]). relacion([sujeto(['Thus,', cytokine, expression, is, highly, heterogeneous, under, mixed, 'conditions,', with, subpopulations, of, cells]), verbo([expressing]), complemento([only, 'IFN-γ,', only, 'IL-4,', both, 'cytokines,', or, neither])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([a, differentiation, scheme, in, which, cells, reflect, uncertainty, through, a, continuously, tuneable, mixed, phenotype, combined, with, a, biased, stochastic, decision, rather, than, a, binary, phenotype, with, a, deterministic, decision])]). relacion([sujeto(['Respiratory', syncytial, virus, '(', 'RSV)', is, the]), verbo([leading]), complemento([global, cause, of, infantile, 'bronchiolitis,', which, is, associated, with, recurrent, wheeze, and, asthma, diagnosis, in, later, life])]). relacion([sujeto(['Th2-driven', disease]), verbo([has]), complemento([been, well, described, under, some, conditions, for, 'RSV-infected', mice])]). relacion([sujeto(['Infected', 'Treg-depleted', mice, lost, significantly, more, weight, than, 'wild-type', 'mice,', indicating]), verbo([enhanced]), complemento([disease])]). relacion([sujeto(['This', enhancement, was, characterized, by]), verbo([increased]), complemento([cellularity, in, the, bronchoalveolar, lavage, '(', 'BAL)', fluid, and, notable, lung, eosinophilia, not, seen, in, control, mice])]). relacion([sujeto(['This', was, accompanied, by, abundant, 'CD4(+)', and, 'CD8(+)', 'T', cells, exhibiting, an]), verbo([activated]), complemento([phenotype, and, induction, of, interleukin, 13, '(', 'IL-13)-', and, 'GATA3-expressing', 'Th2-type', 'CD4(+)', 'T', cells, that, remained, present, in, the, airways, even, 14, days, after, infection])]). relacion([sujeto(['Therefore,', 'Treg', cells, perform, vital, 'anti-inflammatory', functions, during, 'RSV', 'infection,']), verbo([suppressing]), complemento([pathogenic, 'T', cell, responses, and, inhibiting, lung, eosinophilia])]). relacion([sujeto(['These', findings]), verbo([provide]), complemento([additional, evidence, that, dysregulation, of, normal, immune, responses, to, viral, infection, may, contribute, to, severe, 'RSV', disease])]). relacion([sujeto(['During', the, 'follow-up', period, '(', 'mean,', 88.7, 'months),', four, 'patients,', including, the, microinvasive, 'patient,', showed, recurrence, with, the, same, grade, and, stage, but, neither, progressed, into, 'muscle-invasive', tumor, nor]), verbo([caused]), complemento([death])]). relacion([sujeto(['Our', results]), verbo([suggest]), complemento([that, urothelial, eddy, is, a, rare, aberrant, histology, of, papillary, urothelial, neoplasms, with, indolent, behavior, and, should, be, discriminated, from, squamous, differentiation, of, urothelial, 'carcinoma,', which, has, a, poor, prognosis])]). relacion([sujeto(['Master', regulators, of, 'Th1', cells, '(', 'T-box']), verbo([expressed]), complemento([in, 'T', 'cells,', 'T-bet),', 'Th17', cells, '(', retinoid, related, orphan, receptor, 'gamma(t),', 'RORγt),', 'Th2', cells, '(', 'GATA', family, of, transcription, factors, 3, ',', 'GATA3)', and, regulatory, 'T', cells, '(', forkhead, box, 'P3,', 'Foxp3)', were, also, determined])]). relacion([sujeto(['Systemic', infusion, of, 'GFP-BMSCs', ameliorated, the, clinical, and, histopathologic, severity, of, 'colitis,', including, body, weight, 'loss,', diarrhea, and, 'inflammation,', and]), verbo([increased]), complemento([survival, '(', 'P', &, 'lt;', 0.05, ')'])]). relacion([sujeto(['MSCs']), verbo([promoted]), complemento([proliferation, of, intestinal, epithelial, cells, and, differentiation, of, intestinal, stem, cells, '(', 'P', &, 'lt;', 0.01, ')'])]). relacion([sujeto(['This', therapeutic, effect, was, mainly]), verbo([mediated]), complemento([by, 'down-regulation', of, both, 'Th1-Th17-driven', autoimmune, and, inflammatory, responses, '(', 'IL-2,', 'TNF-α,', 'IFN-γ,', 'T-bet;', 'IL-6,', 'IL-17,', 'RORγt),', and, by, 'up-regulation', of, 'Th2', activities, '(', 'IL-4,', 'IL-10,', 'GATA-3)', '(', 'P', &, 'lt;', 0.05, ')'])]). relacion([sujeto(['MSCs', also]), verbo([induced]), complemento([activated, 'CD4(+)CD25(+)Foxp3(+)', regulatory, 'T', cells, '(', 'TGF-β,', 'IL-10,', 'Foxp3)', with, a, suppressive, capacity, on, 'Th1-Th17', effecter, responses, and, promoted, 'Th2', differentiation, in, vivo, '(', 'P', &, 'lt;', 0.05, ')'])]). relacion([sujeto(['Lhx2']), verbo([inhibited]), complemento([differentiation, of, 'HPCs', into, mature, hematopoietic, cells, and, this, effect, would, lead, to, accumulation, of, 'HSC-like', cells])]). relacion([sujeto(['LIM-HD', factors]), verbo([interact]), complemento([with, 'LIM', domain, binding, '(', 'Ldb)', protein, and, this, interaction, abrogates, binding, of, 'LIM-only', '(', 'Lmo)', protein, to, 'Ldb'])]). relacion([sujeto(['We']), verbo([found]), complemento([that, one, of, 'Lmo', 'protein,', 'Lmo2,', was, unstable, due, to, dissociation, of, 'Lmo2', from, 'Ldb1', in, the, presence, of, 'Lhx2'])]). relacion([sujeto(['This', effect, of, 'Lhx2', on, the, amount, of, 'Lmo2', contributed, into, accumulation, of, 'HSC-like', 'cells,', since, enforced, expression, of, 'Lmo2', into, 'HSC-like', cells]), verbo([inhibited]), complemento([their, 'self-renewal'])]). relacion([sujeto(['Expression', of, 'Gata3', and, 'Tal1/Scl', was]), verbo([increased]), complemento([in, 'HSC-like', cells, and, enforced, expression, of, 'Lmo2', reduced, expression, of, 'Gata3', but, not, 'Tal1/Scl'])]). relacion([sujeto(['Enforced', expression, of, 'Gata3', into, 'HPCs']), verbo([inhibited]), complemento([mature, hematopoietic, cell, 'differentiation,', whereas, 'Gata3-knockdown', abrogated, the, 'Lhx2-mediated', expansion, of, 'HPCs'])]). relacion([sujeto(['We', propose, that, multiple, transcription, 'factors/cofactors', are]), verbo([involved]), complemento([in, the, 'Lhx2-mediated', expansion, of, 'HSC-like', cells, from, 'ESCs'])]). relacion([sujeto(['Translating', the, developmental, program, encoded, in, the, genome, into, cellular, and, morphogenetic, functions]), verbo([requires]), complemento([the, deployment, of, elaborate, gene, regulatory, networks, '(', 'GRNs)'])]). relacion([sujeto(['GRNs', are, especially, crucial, at, the, onset, of, organ, development, where, a, few, regulatory, signals, establish, the, different, programs]), verbo([required]), complemento([for, tissue, organization])]). relacion([sujeto(['In', the, renal, system, primordium, '(', the, 'pro/mesonephros),', important, regulators]), verbo([have]), complemento([been, identified, but, their, hierarchical, and, regulatory, organization, is, still, elusive])]). relacion([sujeto(['Here,', we]), verbo([have]), complemento([performed, a, detailed, analysis, of, the, 'GRN', underlying, mouse, 'pro/mesonephros', development])]). relacion([sujeto(['We']), verbo([find]), complemento([that, a, core, regulatory, subcircuit, composed, of, 'Pax2/8,', 'Gata3', and, 'Lim1', turns, on, a, deeper, layer, of, transcriptional, regulators, while, activating, effector, genes, responsible, for, cell, signaling, and, tissue, organization])]). relacion([sujeto(['Hence,', the, 'pro/mesonephros', 'GRN', links, together, several, essential, genes]), verbo([regulating]), complemento([tissue, morphogenesis])]). relacion([sujeto([22, q11, deletion, syndrome, is, one, of, the, most, common, chromosomal, deletion, syndromes, and, is, usually]), verbo([caused]), complemento([by, a, 1.5, -, 3.0, 'Mb', deletion, at, chromosome, 22, q11])]). relacion([sujeto(['This', region, is, the, locus, for, 'hypoparathyroidism,', 'deafness,', and, renal, dysplasia, '(', 'HDR)', syndrome]), verbo([caused]), complemento([by, haploinsufficiency, of, 'GATA3'])]). relacion([sujeto(['This', is, the, first, known, case]), verbo([report]), complemento([of, the, 'co-occurrence', of, 22, q11, deletion, syndrome, and, 'HDR', syndrome])]). relacion([sujeto([')', is, one, the, most, commonly, consumed, legumes, that]), verbo([requires]), complemento([an, in, depth, understanding, of, its, allergenicity])]). relacion([sujeto(['Therefore,', the, aim, of, this, study, was, to, explore, the, allergenicity, of, red, kidney, bean, proteins, following, oral, exposure, in, 'BALB/c', mice, and, elucidate, the, levels, of, 'Th1/Th2', transcription, factors]), verbo([induced]), complemento([by, red, kidney, bean, proteins, in, rat, basophilic, leukemia, cells, '(', 'RBL-2H3', 'cells)', passively, sensitized, with, the, sera, of, red, kidney, bean, sensitized, mice])]). relacion([sujeto(['Red', kidney, bean, proteins, showed]), verbo([enhanced]), complemento([levels, of, total, and, specific, 'IgE,', anaphylactic, 'symptoms,', thymic, stromal, lymphopoietin, '(', 'TSLP)', and, peritoneal, albumin, over, control])]). relacion([sujeto(['Enhanced']), verbo([release]), complemento([of, 'β-hexosaminidase', along, with, up, regulated, expressions, of, 'GATA-3,', 'STAT-6,', 'T-bet,', 'c-MAF', and, 'NFAT', were, observed, in, the, 'RBL-2H3', cells, exposed, with, red, kidney, bean, proteins, when, compared, to, that, of, the, controls])]). relacion([sujeto(['Taken', 'together,', exposure, of, red, kidney, bean, proteins, may]), verbo([cause]), complemento([allergic, symptoms, in, mice, and, the, ambivalent, effect, on, 'Th2/Th1', transcription, factors, in, 'RBL-2H3', cells])]). relacion([sujeto(['GATA-3', is, a, transcription, factor]), verbo([involved]), complemento([in, human, growth, and, development])]). relacion([sujeto(['Recent', studies]), verbo([found]), complemento([its, association, with, breast, 'cancer,', 'however,', its, expression, profile, in, renal, cell, carcinoma, '(', 'RCC)', has, not, been, investigated])]). relacion([sujeto(['In', 'summary,', our, present, study, clarifies, that, the, aberrant, expression, profile, of, 'GATA-3', in, human, 'RCC', is, possibly]), verbo([involved]), complemento([with, 'tumorigenesis,', and, the, complicated, mechanism, is, worthy, of, further, investigation])]). relacion([sujeto(['TIM-3', mRNA, levels, of, active, 'ITP', patients, were, significantly]), verbo([decreased]), complemento([to, '(', 29, ±, 16, ')', '%', of, that, of, 'control,', 'TIM-1', mRNA, levels, of, active, 'ITP', patients, increased, to, '(', 3.2, ±, 2.18, ')', folds, of, that, of, 'control,', but, the, difference, was, not, significant])]). relacion([sujeto([5, ')', and, the, expression, of, 'GATA3', was]), verbo([decreased]), complemento([by, 14, '%', folds, '(', 'P<0'])]). relacion([sujeto(['The', biology, of, this, unusual, cancer, is, not, understood, 'and,', 'consequently,', no, potential]), verbo([targets]), complemento([for, treatments, are, currently, available])]). relacion([sujeto(['There']), verbo([has]), complemento([been, an, exponential, increase, in, the, number, of, commercially, available, tumor, profiling, services])]). relacion([sujeto(['Herein,', we]), verbo([report]), complemento([a, case, of, metastatic, malignant, phyllodes, tumor, for, which, a, comprehensive, molecular, analysis, was, performed, by, using, 'Clinical', 'Laboratory', 'Improvement', 'Amendments', '(', 'CLIA)-certified', 'labs,', providing, new, insights, into, the, potential, opportunities, for, molecularly, targeted, therapies, for, this, extremely, rare, disease])]). relacion([sujeto(['Next-generation', sequencing, showed, 3, aberrant, 'genes:']), verbo([activating]), complemento([mutation, 'Q61L', on, 'NRAS;', inactivating, mutations, 'Q504*', and, 'K740*', on, 'RB1;', and, 'TP53', loss])]). relacion([sujeto(['Immunohistochemical', analysis, for, relevant, markers, showed, a, positive, staining, for, 'transducing-like', enhancer, of, split, '(', 'TLE)', 3, ;, secreted, protein, acidic, and, rich, in, cysteine, '(', 'SPARC)', was]), verbo([expressed]), complemento([at, 2, -, 3, +, in, the, cytoplasm, of, the, tumors, 'cells,', whereas, mammalian, target, of, rapamycin, '(', 'mTOR)', was, expressed, up, to, 2, +, in, the, nuclei, of, the, tumor, cells])]). relacion([sujeto(['We', also]), verbo([found]), complemento([markers, for, sensitivity, to, 'taxane-based', 'therapies,', especially, 'albumin-bound', paclitaxel])]). relacion([sujeto(['Exploring', the, biology, of, rare, malignancies, by, 'CLIA', certified, labs, may, be, reasonable, strategy, for, the, development, of]), verbo([targeted]), complemento([treatments])]). relacion([sujeto(['The', differentiation, of, 'CD4', helper, 'T', cells, into, specialized, effector, lineages]), verbo([has]), complemento([provided, a, powerful, model, for, understanding, immune, cell, differentiation])]). relacion([sujeto(['Distinct', lineages]), verbo([have]), complemento([been, defined, by, differential, expression, of, signature, cytokines, and, the, 'lineage-specifying', transcription, factors, necessary, and, sufficient, for, their, production])]). relacion([sujeto(['The', traditional, paradigm, of, differentiation, towards, 'Th1', and, 'Th2', subtypes, driven, by, 'T-bet', and, 'GATA3,', 'respectively,']), verbo([has]), complemento([been, extended, to, incorporate, additional, 'T', cell, lineages, and, transcriptional, regulators])]). relacion([sujeto(['Technological', advances]), verbo([have]), complemento([expanded, our, view, of, these, 'lineage-specifying', transcription, factors, to, the, whole, genome, and, revealed, unexpected, interplay, between, them])]). relacion([sujeto(['From', these, 'data,', it, is, becoming, clear, that, lineage, specification, is, more, complex, and, plastic, than, previous, models, might]), verbo([have]), complemento([suggested])]). relacion([sujeto(['Here,', we, present, an, overview, of, the, different, forms, of, transcription, factor, interplay, that]), verbo([have]), complemento([been, identified, and, how, 'T', cell, phenotypes, arise, as, a, product, of, this, interplay, within, complex, regulatory, networks])]). relacion([sujeto(['We', also]), verbo([suggest]), complemento([experimental, strategies, that, will, provide, further, insight, into, the, mechanisms, that, underlie, 'T', cell, lineage, specification, and, plasticity])]). relacion([sujeto(['The', accumulated, uremic, toxins]), verbo([inhibit]), complemento([the, expression, of, various, renal, transporters, and, this, inhibition, may, further, reduce, renal, function, and, subsequently, cause, the, accumulation, of, uremic, toxins])]). relacion([sujeto(['However,', the, precise, mechanism, of, the, nephrotoxicity, of, uremic, toxins, on, renal, transport]), verbo([has]), complemento([been, poorly, understood])]). relacion([sujeto(['Here', we]), verbo([report]), complemento([that, indoxyl, 'sulfate,', one, of, the, potent, uremic, 'toxins,', directly, suppresses, the, 'renal-specific', organic, anion, transporter, 'SLCO4C1', expression, through, a, transcription, factor, 'GATA3'])]). relacion([sujeto(['The', promoter, region, of, 'SLCO4C1', gene]), verbo([has]), complemento([several, 'GATA', 'motifs,', and, indoxyl, sulfate, 'up-regulated', 'GATA3', mRNA, and, subsequently, 'down-regulated', 'SLCO4C1', mRNA])]). relacion([sujeto(['Overexpression', of, 'GATA3', significantly, reduced, 'SLCO4C1', 'expression,', and, silencing, of, 'GATA3']), verbo([increased]), complemento(['SLCO4C1', expression, vice, versa])]). relacion([sujeto(['Administration', of, indoxyl, sulfate, in, rats, reduced, renal, expression, of, slco4c1, and, under, this, 'condition,', plasma, level, of, 'guanidinosuccinate,', one, of, the, preferable, substrates, of, 'slco4c1,', was, significantly]), verbo([increased]), complemento([without, changing, plasma, creatinine])]). relacion([sujeto(['Furthermore,', in, 5, /, 6, nephrectomized, 'rats,', treatment, with, oral, adsorbent, 'AST-120', significantly]), verbo([decreased]), complemento([plasma, indoxyl, sulfate, level, and, conversely, increased, the, expression, of, 'slco4c1,', following, the, reduction, of, plasma, level, of, guanidinosuccinate])]). relacion([sujeto(['These', data]), verbo([suggest]), complemento([that, the, removal, of, indoxyl, sulfate, and, blocking, its, signal, pathway, may, help, to, restore, the, 'SLCO4C1-mediated', renal, excretion, of, uremic, toxins, in, 'CKD'])]). relacion([sujeto(['Since', the, initial, discovery, that, 'OCT4,', 'SOX2,', 'KLF4,', and, 'c-MYC', overexpression, sufficed, for, the, induction, of, pluripotency, in, somatic, 'cells,', methodologies, replacing, the, original, factors]), verbo([have]), complemento([enhanced, our, understanding, of, the, reprogramming, process])]). relacion([sujeto(['However,', unlike, in, 'mouse,', 'OCT4']), verbo([has]), complemento([not, been, replaced, successfully, during, reprogramming, of, human, cells])]). relacion([sujeto(['Here', we]), verbo([report]), complemento([on, a, strategy, to, accomplish, this, replacement])]). relacion([sujeto(['Through', a, combination, of, transcriptome, and, bioinformatic, analysis, we]), verbo([have]), complemento([identified, factors, previously, characterized, as, being, lineage, specifiers, that, are, able, to, replace, 'OCT4', and, 'SOX2', in, the, reprogramming, of, human, fibroblasts])]). relacion([sujeto(['Cyp11a1', expression, is]), verbo([increased]), complemento([in, activated, 'T', cells])]). relacion([sujeto(['Peanut', sensitization, and, challenge, resulted, in, 'diarrhea,', 'inflammation,', and]), verbo([increased]), complemento([levels, of, 'Cyp11a1,', 'IL13,', and, 'IL17A', mRNA, in, the, small, intestine])]). relacion([sujeto(['Inhibition', of, 'Cyp11a1', with, 'AMG']), verbo([prevented]), complemento([allergic, diarrhea, and, inflammation])]). relacion([sujeto(['AMG', treatment]), verbo([decreased]), complemento(['IL13', and, 'IL17A', mRNA, expression, in, the, small, intestine, without, affecting, 'Cyp11a1', mRNA, or, protein, levels])]). relacion([sujeto(['In', vitro, the, inhibitor]), verbo([decreased]), complemento(['IL13', and, 'IL17A', mRNA, and, protein, levels, in, differentiated, 'T(H)2', and, 'T(H)17', 'CD4', 'T', 'cells,', 'respectively,', without, affecting, 'GATA3,', retinoic, 'acid-related', orphan, receptor, γt, '(', 'RORγt),', or, 'T(H)1', cells, and, 'IFNG', and, 'T-bet', expression])]). relacion([sujeto(['Short', hairpin, 'RNA-mediated', silencing, of, 'Cyp11a1', in, polarized, 'T(H)2', 'CD4', 'T', cells, significantly]), verbo([decreased]), complemento([pregnenolone, and, 'IL13', mRNA, and, protein, levels])]). relacion([sujeto(['Cyp11a1', plays, an, important, role, in, the, development, of, peanut, 'allergy,']), verbo([regulating]), complemento(['peanut-induced', allergic, responses, through, effects, on, 'steroidogenesis,', an, essential, pathway, in, 'T(H)2', differentiation])]). relacion([sujeto(['Cyp11a1', thus, serves, as, a, novel]), verbo([target]), complemento([in, the, regulation, and, treatment, of, peanut, allergy])]). relacion([sujeto(['Of', equal, importance, are, studies, on, how, probiotics, might]), verbo([prevent]), complemento([or, delay, disease, in, healthy, individuals])]). relacion([sujeto(['To']), verbo([gain]), complemento([more, insight, in, how, different, bacterial, strains, may, modulate, the, healthy, intestinal, immune, 'system,', we, investigated, the, effect, of, the, food, derived, bacterial, strains, 'L'])]). relacion([sujeto(['All', three, bacterial, strains]), verbo([induced]), complemento([an, upregulation, of, activity, and, numbers, of, 'CD11c(+)', 'MHCII(+)', 'DCs', in, the, 'immune-sampling', 'Peyer\'s', 'Patches'])]). relacion([sujeto([salivarius, 'UCC118']), verbo([induced]), complemento([activation, in, both, 'CD4', and, 'CD8', positive, 'T-cells', while, 'L'])]). relacion([sujeto([plantarum, 'WCFS1']), verbo([induced]), complemento([a, more, regulatory, phenotype])]). relacion([sujeto([plantarum, 'WCFS1']), verbo([decreased]), complemento([the, 'Th1/Th2', ratio, in, the, 'SILP'])]). relacion([sujeto([lactis, 'MG1363']), verbo([decreased]), complemento([the, expression, of, the, 'GATA-3', and, 'T-bet', in, the, 'SILP'])]). relacion([sujeto(['Our', 'strain-specific', results]), verbo([suggest]), complemento([that, unspecified, application, of, probiotics, may, not, be, very, effective])]). relacion([sujeto(['Our', data, also, indicate, that, selection, of, specific, probiotic, strain, activities, on, the, basis, of, responses, in, healthy, mice, may, be, a, promising, strategy, to, specifically]), verbo([stimulate]), complemento([or, suppress, immunity, in, specific, parts, of, the, intestine])]). relacion([sujeto(['Although', 'FASD', are]), verbo([caused]), complemento([by, prenatal, ethanol, 'exposure,', 'FASD', are, thought, to, be, genetically, 'modulated,', although, the, genes, regulating, sensitivity, to, ethanol, teratogenesis, are, largely, unknown])]). relacion([sujeto(['We']), verbo([found]), complemento([that, only, 'platelet-derived', growth, factor, receptor, alpha, '(', 'pdgfra)', interacted, with, ethanol, during, zebrafish, craniofacial, development])]). relacion([sujeto(['In', 'zebrafish,', untreated, pdgfra, mutants]), verbo([have]), complemento([cleft, palate, due, to, defective, neural, crest, cell, 'migration,', whereas, pdgfra, heterozygotes, develop, normally])]). relacion([sujeto(['Ethanol-exposed', pdgfra, mutants]), verbo([have]), complemento([profound, craniofacial, defects, that, include, the, loss, of, the, palatal, skeleton, and, hypoplasia, of, the, pharyngeal, skeleton])]). relacion([sujeto(['Furthermore,', ethanol, treatment, revealed, latent, 'haploinsufficiency,']), verbo([causing]), complemento([palatal, defects, in, '∼62%', of, pdgfra, heterozygotes])]). relacion([sujeto(['This', protective, role, is]), verbo([mediated]), complemento([by, the, 'PI3K/mTOR', pathway])]). relacion([sujeto(['Collectively,', our, results]), verbo([suggest]), complemento([a, model, where, combined, genetic, and, environmental, inhibition, of, 'PI3K/mTOR', signaling, leads, to, variability, within, 'FASD'])]). relacion([sujeto(['The', oncogenic, transcription, factor, 'TAL1/SCL', is, aberrantly]), verbo([expressed]), complemento([in, 60, '%', of, cases, of, human, 'T', cell, acute, lymphoblastic, leukemia, '(', 'T-ALL)', and, initiates, 'T-ALL', in, mouse, models])]). relacion([sujeto(['The', most, dynamically]), verbo([regulated]), complemento([miRNA, was, 'miR-223,', which, is, bound, at, its, promoter, and, 'up-regulated', by, the, 'TAL1', complex])]). relacion([sujeto(['Overexpression', of, 'miR-223', also]), verbo([leads]), complemento([to, marked, 'down-regulation', of, 'FBXW7', protein, 'expression,', whereas, knockdown, of, 'TAL1', leads, to, 'up-regulation', of, 'FBXW7', protein, 'levels,', with, a, marked, reduction, of, its, substrates, 'MYC,', 'MYB,', 'NOTCH1,', and, 'CYCLIN', 'E'])]). relacion([sujeto(['We', conclude, that, 'TAL1-mediated', 'up-regulation', of, 'miR-223']), verbo([promotes]), complemento([the, malignant, phenotype, in, 'T-ALL', through, repression, of, the, 'FBXW7', tumor, suppressor])]). relacion([sujeto(['We']), verbo([have]), complemento([studied, the, signal, transduction, pathways, critical, for, the, cytokine, expression, and, development, of, 'NH', cell])]). relacion([sujeto(['Either', stimulation, with, 'IL-33', or, a, combination, of, 'IL-2', and, 'IL-25']), verbo([induced]), complemento([p38, activation, and, phosphorylation, of, 'GATA3', in, 'NH', 'cells,', and, the, phosphorylated, form, of, 'GATA3', bound, to, the, 'IL-5', and, 'IL-13', promoters])]). relacion([sujeto(['We']), verbo([report]), complemento([here, that, 'GATA3', promotes, cell, proliferation, and, tumorigenesis, by, facilitating, the, 'G1/S', transition, through, its, transcription, regulation, of, the, 'CCND1', gene, in, breast, cancer, cells])]). relacion([sujeto(['We']), verbo([found]), complemento([that, 'GATA3', is, physically, associated, with, 'poly-ADP', ribose, 'polymerase-1', '(', 'PARP1),', an, enzyme, modifying, nuclear, proteins, by, 'poly(ADP-ribosyl)ation'])]). relacion([sujeto(['We', showed, that, 'PARP1']), verbo([acts]), complemento([as, a, transcription, coactivator, for, 'GATA3', in, breast, cancer, cells, and, demonstrated, that, 'GATA3', cooperates, with, 'PARP1', in, transactivation, of, the, 'CCND1', gene])]). relacion([sujeto(['We', demonstrated, that, 'PARP1', competes, with, linker, histone, 'H1', to]), verbo([maintain]), complemento([a, transcriptional, competent, chromatin, environment, for, 'CCND1', gene])]). relacion([sujeto(['Our', results, unveiled, a, molecular, basis, for, the, coordinated, regulation, between, 'GATA3', and, 'PARP1', in, transcription, 'activation,']), verbo([providing]), complemento([a, mechanism, for, 'GATA3', in, breast, carcinogenesis])]). relacion([sujeto(['The', key, molecular, events]), verbo([required]), complemento([for, the, formation, of, ductal, carcinoma, in, situ, '(', 'DCIS)', and, its, progression, to, invasive, breast, carcinoma, have, not, been, defined])]). relacion([sujeto(['Here,', we, show, that, the]), verbo([nuclear]), complemento([receptor, coactivator, amplified, in, breast, cancer, 1, '(', 'AIB1)', is, expressed, at, low, levels, in, normal, breast, but, is, highly, expressed, in, 'DCIS', lesions])]). relacion([sujeto(['Reduction', of, 'AIB1', in, 'MCFDCIS', 'cells,', both, before, 'DCIS', development, or, in, existing, 'MCFDCIS', lesions, in, 'vivo,']), verbo([inhibited]), complemento([tumor, growth, and, led, to, 'smaller,', necrotic, lesions])]). relacion([sujeto(['AIB1', reduction, in, 'MCFDCIS', cells, was, correlated, with, significant, reduction, in, the, 'CD24-/CD44+', breast, 'cancer-initiating', cell, '(', 'BCIC)', 'population,', and, a]), verbo([decrease]), complemento([in, myoepithelial, progenitor, cells, in, the, 'DCIS', lesions, in, vitro, and, in, vivo])]). relacion([sujeto(['The']), verbo([loss]), complemento([of, 'AIB1', in, 'MCFDCIS', cells, was, also, accompanied, by, a, loss, of, expression, of, 'NOTCH', 2, ',', 3, and, 4, ',', 'JAG2,', 'HES1,', 'GATA3,', human, epidermal, growth, factor, receptor, 2, '(', 'HER2)', and, 'HER3', in, vivo])]). relacion([sujeto(['These', signaling, molecules]), verbo([have]), complemento([been, associated, with, differentiation, of, breast, epithelial, progenitor, cells])]). relacion([sujeto(['These', data, indicate, that, 'AIB1']), verbo([has]), complemento([a, central, role, in, the, initiation, and, maintenance, of, 'DCIS', and, that, reduction, of, 'AIB1', causes, loss, of, 'BCIC,', loss, of, components, of, the, 'NOTCH,', 'HER2', and, 'HER3', signaling, pathways, and, fewer, 'DCIS', myoepithelial, progenitor, cells, in, vivo])]). relacion([sujeto(['We', propose, that]), verbo([increased]), complemento([expression, of, 'AIB1,', through, the, maintenance, of, 'BCIC,', facilitates, formation, of, 'DCIS,', a, necessary, step, before, development, of, invasive, disease])]). relacion([sujeto(['Role', of, 'inflammation-induced', oxidative, stress, in, the, pathogenesis, and, progression, of, chronic, inflammatory, airways, diseases]), verbo([has]), complemento([received, increasing, attention, in, recent, years])]). relacion([sujeto(['Nuclear', factor, erythroid, 2, -, related, factor, 2, is, the, primary, transcription, factor, that]), verbo([regulates]), complemento([the, expression, of, antioxidant, and, detoxifying, enzymes])]). relacion([sujeto(['Walther,', a, vegetable, consumed, in, 'Taiwan,']), verbo([has]), complemento([been, used, in, folk, medicine, for, protection, against, liver, injury, through, elevating, antioxidation])]). relacion([sujeto(['Recently,', we]), verbo([found]), complemento([that, gallic, acid, is, an, active, compound, of, 'Graptopetalum', paraguayense, 'E'])]). relacion([sujeto(['Walther,', which]), verbo([has]), complemento([been, reported, to, inhibit, 'T-helper', 2, cytokines])]). relacion([sujeto(['Walther', ethanolic, extracts, '(', 'GPE)', clearly]), verbo([inhibited]), complemento([airway, 'inflammation,', mucus, cell, 'hyperplasia,', and, eosinophilia, in, 'OVA-challenged', mice])]). relacion([sujeto(['Additionally,', 'GPE', also]), verbo([prevented]), complemento(['T-cell', infiltration, and, 'Th2', 'cytokines,', including, 'interleukin-', '(', 'IL-)4,', 'IL-5,', and, 'IL-13', generations, in, bronchial, alveolar, lavage, fluid])]). relacion([sujeto(['The', adhesion, molecules, 'ICAM-1', and, 'VCAM-1', were, substantially, reduced, by, 'GPE', treatment]), verbo([mediated]), complemento([by, 'Nrf2', activation])]). relacion([sujeto(['Moreover,', 'GPE', attenuated, 'GATA3', expression, and]), verbo([inhibited]), complemento(['Th2', signals, of, the, 'T', cells])]). relacion([sujeto(['These', findings]), verbo([suggested]), complemento([that, 'GPE', ameliorated, the, development, of, airway, inflammation, through, immune, regulation])]). relacion([sujeto(['The', investigations, of, genomic, and, molecular, aberrations, in, 'MPNSTs', which, detect, many, chromosomal, 'aberrations,', pathway, 'abnormalities,', and, specific, molecular, aberrant, events, would, supply, multiple, potential, therapy]), verbo([targets]), complemento([and, contribute, to, achievement, of, personalized, medicine])]). relacion([sujeto(['The']), verbo([involved]), complemento([genes, in, the, significant, gains, aberrations, include, 'BIRC5,', 'CCNE2,', 'DAB2,', 'DDX15,', 'EGFR,', 'DAB2,', 'MSH2,', 'CDK6,', 'HGF,', 'ITGB4,', 'KCNK12,', 'LAMA3,', 'LOXL2,', 'MET,', and, 'PDGFRA'])]). relacion([sujeto(['The']), verbo([involved]), complemento([genes, in, the, significant, deletion, aberrations, include, 'CDH1,', 'GLTSCR2,', 'EGR1,', 'CTSB,', 'GATA3,', 'SULT2A1,', 'GLTSCR2,', 'HMMR/RHAMM,', 'LICAM2,', 'MMP13,', 'p16/INK4a,', 'RASSF2,', 'NM-23H1,', and, 'TP53'])]). relacion([sujeto(['These', genetic, aberrations]), verbo([involve]), complemento([in, several, important, signaling, pathways, such, as, 'TFF,', 'EGFR,', 'ARF,', 'IGF1R', signaling, pathways])]). relacion([sujeto(['The', genomic, and, molecular, aberrations, of, 'EGFR,', 'IGF1R,', 'SOX9,', 'EYA4,', 'TOP2A,', 'ETV4,', and, 'BIRC5', exhibit, great, promise, as, personalized, therapeutic]), verbo([targets]), complemento([for, 'MPNST', patients])]). relacion([sujeto(['In', 'addition,', a, marked]), verbo([decrease]), complemento([in, plasma, 'IL-4', levels, was, observed, in, the, psoriasis, 'group,', while, no, differences, were, observed, with, regard, to, levels, of, 'IFN-γ', and, 'Th2', between, patients, and, normal, subjects])]). relacion([sujeto(['Furthermore,', a, clear, correlation, between]), verbo([decreased]), complemento(['IL-4', mRNA, expression, and, 'IL-4', '(', 'P', &, 'lt;', 0.05, ')', was, revealed])]). relacion([sujeto(['These', results]), verbo([suggested]), complemento([that, altered, balance, between, 'Th1', and, 'Th2', cells, transcription, factor, genes, and, they, products, may, be, implicated, in, the, pathogenesis, of, psoriasis])]). relacion([sujeto(['GATA3', also, plays, important, roles, in]), verbo([maintaining]), complemento(['Th2', cell, function, and, in, continuous, chromatin, remodeling, of, 'Th2', cytokine, gene, loci])]). relacion([sujeto(['However,', it, is, unclear, whether, continuous, expression, of, 'GATA3', is]), verbo([required]), complemento([to, maintain, the, expression, of, various, other, 'Th2-specific', genes])]). relacion([sujeto(['Moreover,', effects, of, a]), verbo([loss]), complemento([of, 'GATA3', expression, in, 'Th2', cells, on, the, expression, of, cytokine, and, cytokine, receptor, genes, were, examined, in, detail])]). relacion([sujeto(['Therefore,', 'GATA3', is]), verbo([required]), complemento([for, the, continuous, expression, of, the, majority, of, 'Th2-specific', genes, involved, in, maintaining, the, 'Th2', cell, identity])]). relacion([sujeto(['However,', 'uptake,', biodistribution, and, pharmacokinetics, of, hgd40]), verbo([have]), complemento([not, been, investigated, yet])]). relacion([sujeto([')', ',', subsequently]), verbo([decreasing]), complemento([over, time, to, 'non-detectable', levels, at, 2, h, p])]). relacion([sujeto(['Repeated', administration, did, not]), verbo([lead]), complemento([to, drug, accumulation, in, plasma, of, dogs, and, rats])]). relacion([sujeto(['These', pharmacokinetic, of, hgd40]), verbo([provide]), complemento([guidance, for, clinical, 'development,', and, support, an, infrequent, and, convenient, dose, administration, regimen])]). relacion([sujeto(['Five', of, these, domains, known, as, 'p3,', 'pMN,', 'p2,', p1, and, p0, are, located, in, the, ventral, spinal, cord, and, each]), verbo([expresses]), complemento([a, unique, code, of, transcription, factors, '(', 'TFs)', that, define, the, molecular, profile, of, progenitor, cells])]). relacion([sujeto(['Using', fate, mapping, and, gene, expression, studies, we, show, that, 'PAX6,', in, addition, to, each, patterning, 'function,', is]), verbo([expressed]), complemento([in, a, group, of, late, born, interneurons, that, derive, from, the, p2, and, p0, domains])]). relacion([sujeto(['The', 'V0', neurons, represent, 'V0v', ventral, neurons]), verbo([expressing]), complemento(['Pax2'])]). relacion([sujeto(['This', study, was, conducted, to, address, which, chemotactic, factors, are]), verbo([involved]), complemento([in, this, condition])]). relacion([sujeto(['We', focused, on, five, chemotactic, 'factors/receptors', '(', 'CCL1-CCR8,', 'CCL17/CCL22-CCR4),', given, that, 'CCR4', and, 'CCR8', are, predominantly]), verbo([expressed]), complemento([in, both, 'Th2', and, 'Tregs'])]). relacion([sujeto(['In', situ, hybridization, revealed, 'CCL1', to, be, predominantly]), verbo([expressed]), complemento([in, the, pancreatic, duct, 'epithelium,', peribiliary, 'glands,', and, vascular, endothelial, cells, including, the, ones, involved, in, obliterative, phlebitis, in, 'IgG4-SC/AIP,', in, contrast, to, 'IgG4(high)', 'PSC', where, this, chemotactic, factor, was, positive, in, several, infiltrating, lymphocytes])]). relacion([sujeto(['CCL1-CCR8', interaction, may, play, a, critical, role, in, lymphocytic, recruitment, in, 'IgG4-SC/AIP,']), verbo([leading]), complemento([to, 'duct-centred', inflammation, and, obliterative, phlebitis])]). relacion([sujeto(['The', results, demonstrated, that, the, 'WBC', count, and, the, absolute, number, of, 'CD3+CD4+', 'T', 'cells,', 'CD3+CD8+', 'T', cells, and, 'CD3‑CD19+', 'B', cells, in, the, peripheral, blood, were]), verbo([increased]), complemento([in, 'PSP‑treated', groups, as, compared, with, the, cyclophosphamide, '(', 'Cy)', group])]). relacion([sujeto(['In', 'addition,', 'PSP', reduced, interleukin, '(', 'IL)‑4', and, 'GATA']), verbo([binding]), complemento([protein, 3, '(', 'GATA‑3)', mRNA, relative, expression, levels, and, elevated, the, ratios, of, 'IL‑2/IL‑4', and, the, transcription, 'factors,', 'T‑box‑containing', 'protein/GATA‑3'])]). relacion([sujeto(['These', observations, indicate, that, the, immunoregulatory, effects, of, 'PSP', are]), verbo([associated]), complemento([with, restoration, of, 'WBC', 'number,', improving, the, absolute, number, of, 'T', lymphocyte, subsets, and, 'B', 'lymphocytes,', inducing, the, 'Th1/Th2', response, and, downregulating, the, negative, immune, 'regulators,', 'Foxp3,', 'PD‑1', and, 'IL‑10'])]). relacion([sujeto(['T-cell', acute, lymphoblastic, leukemia, '(', 'T-ALL)', is]), verbo([caused]), complemento([by, a, defect, in, 'T-cell', maturation, to, the, mature, 'T', cell])]). relacion([sujeto(['This', study, uses, 'Jurkat', 'T', 'cells,', as, a, 'well-established', model, for, in, vitro, study, of, 'T-ALL', to, investigate, the, role, of, the, microRNA, '(', 'miRNA),', 'miR-146a,', on, gene, expressions]), verbo([involved]), complemento([in, 'T-cell', differentiation])]). relacion([sujeto(['The', permanent, 'over-expression', of, 'miR-146a', was, established, using, a, lentivector, that]), verbo([expressed]), complemento(['GFP', 'hsa-mir-146a', miRNA])]). relacion([sujeto(['There', was, a, 'significant,', moderate, 'down-regulation', in, the, expressions, of, 'Notch1,', 'LIM-domain', only, '(', 'Lmo2),']), verbo([son]), complemento([of, sevenless, 1, '(', 'SOS1),', 'Ikaros,', and, signal, transducer, and, activator, of, transcription, 3, '(', 'STAT3)'])]). relacion([sujeto(['Our', results, indicated, that, ectopic, expression, of, 'miR-146a', could, not, independently]), verbo([induce]), complemento([differentiation, in, lymphoblastic, cells])]). relacion([sujeto(['However,', the, expression, of, multiple, genes]), verbo([involved]), complemento([in, 'T-cell', differentiation, and, 'T-cell', 'CD', markers, were, found, to, be, affected])]). relacion([sujeto(['These', results]), verbo([have]), complemento([suggested, a, potential, tumor, 'suppressive,', immunomodulatory, and, cell, activator, role, for, 'miR146-a'])]). relacion([sujeto(['Our', objective, was, to, investigate, the, mechanism, of, the, inhibitory, effect, of, triptolide, on, 'interleukin-13', '(', 'IL-13)', gene, expression, in]), verbo([activated]), complemento(['T', lymphocytes])]). relacion([sujeto(['Peripheral', blood, mononuclear, cells, '(', 'PBMC)', and, 'Hut-78', cells, were]), verbo([stimulated]), complemento([with, 'anti-CD3/CD28', with, or, without, 'co-incubation', with, triptolide])]). relacion([sujeto(['The', intracellular, distribution, profile, of, transcription, factor, 'GATA3', and]), verbo([nuclear]), complemento([factor, of, activated, 'T', cells, '(', 'NFAT1)', were, analysed, by, 'Western', blotting])]). relacion([sujeto(['The']), verbo([binding]), complemento([rates, of, 'GATA3', and, 'NFAT1', to, the, promoter, sequence, of, 'IL-13', were, analysed, by, chromatin, immunoprecipitation, '(', 'ChIP)', 'PCR'])]). relacion([sujeto(['In', 'PBMC,', the]), verbo([release]), complemento([of, 'IL-13', was, dependent, on, 'anti-CD3/CD28', stimulation])]). relacion([sujeto(['Its']), verbo([release]), complemento([could, be, inhibited, by, triptolide, at, the, concentration, of, 500, nmol])]). relacion([sujeto(['In', 'Hut-78', 'cells,', 'IL-13', mRNA, and, protein, expression, were]), verbo([increased]), complemento([with, 'anti-CD3/CD28', stimulation, and, significantly, inhibited, by, incubation, with, 28, nmol, triptolide])]). relacion([sujeto(['This', concentration, of, triptolide, also, significantly]), verbo([inhibited]), complemento([the, nuclear, translocation, of, 'GATA3', and, 'NFAT1', reducing, the, binding, rate, to, the, 'IL-13', gene, promoter])]). relacion([sujeto(['Triptolide']), verbo([inhibits]), complemento(['IL-13', gene, transcription, and, protein, expression, by, inhibiting, 'GATA3', and, 'NFAT1', nuclear, translocation, and, their, binding, rates, to, the, 'IL-13', gene, promoter, region])]). relacion([sujeto(['The', in, vitro, and, in, vivo, results, demonstrated, that, yerba, mate, extract, 'down-regulated', the, expression, of, genes, that]), verbo([regulate]), complemento(['adipogenesis,', such, as, 'Creb-1and', 'C/EBPα,', and, the, extract, 'up-regulated', the, expression, of, genes, related, to, the, inhibition, of, 'adipogenesis,', including, 'Dlk1,', 'Gata2,', 'Gata3,', 'Klf2,', 'Lrp5,', 'Pparγ2,', 'Sfrp1,', 'Tcf7l2,', 'Wnt10b,', and, 'Wnt3a'])]). relacion([sujeto(['In', 'summary,', it, was, demonstrated, that, yerba, mate, and, its, bioactive, compounds]), verbo([regulate]), complemento([the, expression, of, genes, related, to, in, vitro, adipogenesis])]). relacion([sujeto(['Furthermore,', yerba, mate, might]), verbo([regulate]), complemento([adipogenesis, through, the, 'Wnt', pathway])]). relacion([sujeto(['Recent', studies]), verbo([have]), complemento([shown, that, 'T', helper, 'type-2', '(', 'Th2)', cells, can, induce, the, apoptosis, of, 'CD4+CD25+', 'Treg', cells, or, resist, the, immunosuppressive, effect, of, 'Treg', cells])]). relacion([sujeto(['Compared', with, healthy, donors, and, patients, with, mild, 'asthma,', the, percent, of, 'CD4+CD25+', 'Treg', cells, and, plasma, 'IL-10', levels, were]), verbo([decreased]), complemento([in, patients, with, moderate, to, severe, asthma])]). relacion([sujeto(['The', ratio, of, 'Th2/Treg', and, their, cytokines, was]), verbo([increased]), complemento([in, allergic, 'asthma,', especially, for, moderate, to, severe, asthma])]). relacion([sujeto(['The', ratio, of, 'GATA-3/Foxp3', mRNA, was, also]), verbo([increased]), complemento([in, allergic, asthma])]). relacion([sujeto(['Furthermore,', the, deficiency, of, 'CD4+CD25+', 'Treg', cells, was]), verbo([associated]), complemento([with, the, 'over-expression', of, 'Th2', response])]). relacion([sujeto(['While', the, mechanism, is, not, well, 'understood,', 'BM-MSCs']), verbo([have]), complemento([been, shown, to, contribute, to, the, immunosuppressive, response, found, in, a, number, of, diseases])]). relacion([sujeto(['The', grafted, 'BM-MSCs', significantly]), verbo([stimulated]), complemento([systemic, and, local, 'interleukin-10', '(', 'IL-10)-secreting', 'T', cell, and, regulatory, 'T', cell, '(', 'Treg)', functions])]). relacion([sujeto(['This', observation, was, correlated, with, an]), verbo([increased]), complemento([percentage, of, 'CD4⁺IL-10⁺', cells, and, 'CD4⁺CD25⁺FoxP3⁺', cells, in, splenic, mononuclear, cells, compared, with, 'H'])]). relacion([sujeto(['Moreover,', inhibitory, cytokines, 'IL-10', and, transforming, growth, 'factor-β1']), verbo([increased]), complemento([in, the, gastric, 'tissue,', while, there, was, a, decrease, in, inflammatory, 'interferon-γ', '(', 'IFN-γ)'])]). relacion([sujeto(['An']), verbo([increase]), complemento([in, 'IL-10-secreting', 'T', cells, and, 'Tregs,', associated, with, increased, expression, of, 'Gata-3', and, 'FoxP3,', generation, of, 'IL-10', in, the, 'supernatant,', and, proliferation, of, gastric, epithelial, cells, '(', 'GECs)', was, observed])]). relacion([sujeto(['The', local, and, systemic, immunosuppression]), verbo([mediated]), complemento([by, 'BM-MSCs', likely, contributed, to, an, environment, that, is, compatible, with, the, development, of, 'H'])]). relacion([sujeto(['We', identify, 'prostate-derived', 'ETS', factor, '(', 'PDEF)', as, a, mediator, of, mammary, luminal, epithelial, 'lineage-specific', gene, expression, and, as, a, factor]), verbo([required]), complemento([for, tumorigenesis, in, a, subset, of, breast, cancers])]). relacion([sujeto(['PDEF', levels, strongly, correlate, with, estrogen, receptor, '(', 'ER)-positive', luminal, breast, 'cancer,', and, 'PDEF', transcription, is, inversely]), verbo([regulated]), complemento([by, 'ER', and, 'GATA3'])]). relacion([sujeto(['Furthermore,', 'PDEF', is, essential, for, luminal, breast, cancer, cell, survival, and, is]), verbo([required]), complemento([in, models, of, endocrine, resistance])]). relacion([sujeto(['We']), verbo([report]), complemento([abnormal, expansions, of, 'CD11b⁺HLA-DR⁺', myeloid, cells, in, peripheral, blood, mononuclear, fractions, of, subjects, with, metastatic, pediatric, sarcomas])]). relacion([sujeto(['Like', classical, 'fibrocytes,', they, display, cell, surface, α, smooth, muscle, 'actin,', collagen, 'I/V,', and]), verbo([mediate]), complemento([angiogenesis])]). relacion([sujeto(['However,', classical, fibrocytes, serve, as, antigen, presenters, and, augment, immune, 'reactivity,', whereas, fibrocytes, from, cancer, subjects]), verbo([suppressed]), complemento(['anti-CD3-mediated', 'T-cell', 'proliferation,', primarily, via, indoleamine, oxidase, '(', 'IDO)'])]). relacion([sujeto(['We', thus, describe, a, novel, subset, of, 'cancer-induced', 'myeloid-derived', suppressor, 'cells,', which, bear, the, phenotypic, and, functional, hallmarks, of, fibrocytes, but]), verbo([mediate]), complemento([immune, suppression])]). relacion([sujeto(['The', combination, of, 'hypoparathyroidism,', 'deafness,', and, renal, anomalies, constitutes, an, unusual, syndrome]), verbo([associated]), complemento([most, commonly, with, haploinsufficiency, in, 'GATA3,', which, encodes, a, transcription, factor, that, binds, to, the, '(', 'A/T)', 'GATA', '(', 'A/G)', consensus, 'DNA', sequence])]). relacion([sujeto(['Sensorineural', hearing]), verbo([loss]), complemento([is, the, most, consistently, expressed, clinical, 'feature,', being, present, in, almost, all, affected, 'individuals,', and, the, combination, of, hypoparathyroidism, and, hearing, impairment, occurs, in, well, over, 90, '%', of, those, 'affected,', with, various, renal, anomalies, being, the, most, heterogeneous, feature, of, the, classic, triad])]). relacion([sujeto(['We', also, include, the, specific, genetic, abnormality, and, renal, anomaly]), verbo([associated]), complemento([with, each, individual, case])]). relacion([sujeto(['HDR', syndrome, is, a, heterogeneous, syndrome, most, commonly]), verbo([associated]), complemento([with, 'GATA3', haploinsufficiency])]). relacion([sujeto(['The', development, of, macrophages, is, a, highly]), verbo([regulated]), complemento([process, requiring, coordination, amongst, transcription, factors])]). relacion([sujeto(['The', 'presence/absence,', relative, 'levels,', 'antagonism,', or, synergy, of, all, transcription, factors]), verbo([involved]), complemento([is, critical, to, directing, lineage, cell, fate, and, differentiation])]). relacion([sujeto(['While', relative, levels, of, many, key, myeloid, transcription, factors]), verbo([have]), complemento([been, determined, in, mammalian, macrophage, 'differentiation,', a, similar, set, of, studies, have, yet, to, be, conducted, in, a, teleost, system])]). relacion([sujeto(['In', this, 'study,', we]), verbo([report]), complemento([on, the, mRNA, levels, of, transcription, factors, '(', 'cebpa,', 'cjun,', 'cmyb,', 'egr1,', 'gata1,', 'gata2,', 'gata3,', 'lmo2,', 'mafb,', 'pax5,', pu])]). relacion([sujeto([1, were, significantly, 'higher,', gata3, and, pax5, mRNA, levels, were, 'lower,', in, monocytes, compared, to, 'progenitors,', and, the, mRNA, levels, of, 'cjun,', 'egr1,', 'gata2,', 'gata3,', mafb, and, pax5, were, significantly]), verbo([decreased]), complemento([in, macrophages, compared, to, progenitor, cells])]). relacion([sujeto(['In', contrast, to, other, irf, family, transcription, factors, 'examined,', irf8, mRNA, levels, were]), verbo([increased]), complemento([in, monocytes, compared, to, progenitors, by, greater, than, 'three-fold,', suggesting, that, irf8, is, important, for, monopoiesis])]). relacion([sujeto(['Group', 2, innate, lymphoid, cells, '(', 'ILC2s;', also, called, 'nuocytes,', innate, helper, 'cells,', or, natural, helper, 'cells)']), verbo([provide]), complemento([protective, immunity, during, helminth, infection, and, play, an, important, role, in, 'influenza-induced', and, allergic, airway, hyperreactivity])]). relacion([sujeto(['Whereas', the, transcription, factor, 'GATA']), verbo([binding]), complemento([protein, 3, '(', 'Gata3)', is, important, for, the, production, of, 'IL-5', and, -, 13, by, 'ILC2s', in, response, to, 'IL-33', or, -, 25, 'stimulation,', it, is, not, known, whether, 'Gata3', is, required, for, 'ILC2', development, from, hematopoietic, stem, cells])]). relacion([sujeto(['In', these, chimeric, 'mice,', in, vivo, administration, of, 'IL-33', or, -, 25, fails, to, expand, 'ILC2', numbers, or, to]), verbo([induce]), complemento([characteristic, 'ILC2-dependent', 'IL-5', or, -, 13, production])]). relacion([sujeto(['Moreover,', 'cell-intrinsic', 'Gata3', expression, is]), verbo([required]), complemento([for, 'ILC2', development, in, vitro, and, in, vivo])]). relacion([sujeto(['Using', mutant, and, transgenic, mice, in, which, 'Gata3', gene, copy, number, is, 'altered,', we, show, that, 'ILC2', generation, from, common, lymphoid, 'progenitors,', as, well, as, 'ILC2', homeostasis, and, cytokine, 'production,', is]), verbo([regulated]), complemento([by, 'Gata3', expression, levels, in, a, 'dose-dependent', fashion])]). relacion([sujeto(['MicroRNAs', '(', 'miRNAs)', are, a, class, of, small, noncoding, 'RNAs', that, control, gene, expression, by]), verbo([targeting]), complemento([mRNAs, and, triggering, either, translational, repression, or, 'RNA', degradation])]). relacion([sujeto(['The', aberrant, expression, of, miRNAs, might, be]), verbo([involved]), complemento([in, human, 'diseases,', including, cancer])]). relacion([sujeto(['However,', the, expression, and, regulation, of, 'miR-206', in, the, developing, mammary, gland]), verbo([has]), complemento([not, yet, been, studied])]). relacion([sujeto(['To', understand, the, effects, of, 'miR-206', on, mammary, gland, 'development,', we]), verbo([have]), complemento([profiled, gene, expression, in, 'scramble-transfected', and, 'miR-206-overexpressing', developing, mammary, buds])]). relacion([sujeto(['The', genes, that, are, potentially]), verbo([regulated]), complemento([by, 'miR-206', in, the, mammary, epithelium, 'and/or', 'mesenchyme,', such, as, 'Tachykinin1', and, 'Gata3,', are, known, to, be, breast, cancer, markers])]). relacion([sujeto(['The', expression, of, 'Wnt,', which, is]), verbo([involved]), complemento([in, gland, 'positioning,', and, of, the, transcription, factors, 'Tbx3', and, 'Lef1,', which, are, essential, for, mammary, gland, 'development,', changes, after, 'miR-206', overexpression])]). relacion([sujeto(['Using', a, mammary, bud, in, vitro, culture, 'system,', we]), verbo([have]), complemento([demonstrated, that, 'miR-206', acts, downstream, of, 'ER-α', during, mammary, gland, growth])]). relacion([sujeto(['Here,', we, established, that, the, 'Ik', interactions, with, 'GATA', transcription, factors, and, 'cyclin-dependent', kinase, 9, '(', 'Cdk9),', a, component, of, the, positive, transcription, elongation, factor, b, '(', 'P-TEFb),', are]), verbo([required]), complemento([for, transcriptional, activation, of, 'Ik', target, genes])]). relacion([sujeto(['A', detailed, dissection, of, 'Ik-GATA', and, 'Ik-Cdk9', protein, interactions, indicated, that, the, 'C-terminal', zinc, finger, domain, of, 'Ik']), verbo([interacts]), complemento([directly, with, the, 'C-terminal', zinc, fingers, of, 'GATA1,', 'GATA2,', and, 'GATA3,', whereas, the, 'N-terminal', zinc, finger, domain, of, 'Ik', is, required, for, interaction, with, the, kinase, and, 'T-loop', domains, of, 'Cdk9'])]). relacion([sujeto(['Moreover,', the, oncogenic, isoform, 'Ik6', did, not, efficiently]), verbo([interact]), complemento([with, 'Cdk9', or, 'GATA', proteins, in, vivo, and, perturbed, 'Cdk9/P-TEFb', recruitment, to, 'Ik', target, 'genes,', thereby, affecting, transcription, elongation])]). relacion([sujeto(['Finally,', characterization, of, a, novel]), verbo([nuclear]), complemento(['Ik', isoform, revealed, that, 'Ik', exon, 6, is, dispensable, for, interactions, with, 'Mi2', and, 'GATA', proteins, but, is, essential, for, the, 'Cdk9', interaction])]). relacion([sujeto(['The', 'T', helper, 17, '(', 'Th17)', cells]), verbo([have]), complemento([been, suggested, to, have, osteoclast, activating, effects, while, 'T', helper, 2, '(', 'Th2)', cells, are, considered, to, have, an, osteoprotective, role, in, periodontitis])]). relacion([sujeto(['The', results, showed, a, significant]), verbo([increase]), complemento([in, the, number, of, markers, of, 'Th17', '(', 'RORC2', and, 'IL-17', 'genes)', compared, to, markers, of, 'Th2', '(', 'GATA-3,', 'IL-4)', in, patients, with, periodontitis, compared, to, controls, '(', 'p≤0'])]). relacion([sujeto(['The', results, show, that, expression, levels, of, 'IL-4,', 'GATA-3,', 'IL-17', and, 'RORC2']), verbo([increase]), complemento([significantly, in, periodontal, lesions, compared, with, the, controls])]). relacion([sujeto(['The', importance, of, the, estrogen, receptor, '(', 'ER)', in, breast, cancer, '(', 'BCa)', development, makes, it, a, prominent]), verbo([target]), complemento([for, therapy])]). relacion([sujeto(['Current', 'treatments,', 'however,']), verbo([have]), complemento([limited, 'effectiveness,', and, hence, the, definition, of, new, therapeutic, targets, is, vital])]). relacion([sujeto(['The', 'ER', is, a, member, of, the]), verbo([nuclear]), complemento([hormone, receptor, superfamily, of, transcription, factors, that, requires, 'co-regulator', proteins, for, complete, regulation])]). relacion([sujeto(['Emerging', evidence]), verbo([has]), complemento([implicated, a, small, number, of, histone, methyltransferase, '(', 'HMT)', and, histone, demethylase, '(', 'HDM)', enzymes, as, regulators, of, 'ER', 'signalling,', including, the, histone, 'H3', lysine, 9, 'tri-/di-methyl', 'HDM', enzyme, 'KDM4B'])]). relacion([sujeto(['Two', recent, independent]), verbo([reports]), complemento([have, demonstrated, that, 'KDM4B', is, required, for, 'ER-mediated', transcription, and, depletion, of, the, enzyme, attenuates, 'BCa', growth, in, vitro, and, in, vivo])]). relacion([sujeto(['Here', we, show, that, 'KDM4B']), verbo([has]), complemento([an, overarching, regulatory, role, in, the, 'ER', signalling, cascade, by, controlling, expression, of, the, 'ER', and, 'FOXA1', 'genes,', two, critical, components, for, maintenance, of, the, 'estrogen-dependent', phenotype])]). relacion([sujeto(['KDM4B']), verbo([interacts]), complemento([with, the, transcription, factor, 'GATA-3', in, 'BCa', cell, lines, and, directly, 'co-activates', 'GATA-3', activity, in, 'reporter-based', experiments])]). relacion([sujeto(['Moreover,', we]), verbo([reveal]), complemento([that, 'KDM4B', recruitment, and, demethylation, of, repressive, 'H3K9me3', marks, within, upstream, regulatory, regions, of, the, 'ER', gene, permits, binding, of, 'GATA-3', to, drive, receptor, expression])]). relacion([sujeto(['Ultimately,', our, findings, confirm, the, importance, of, 'KDM4B', within, the, 'ER', signalling, cascade, and, as, a, potential, therapeutic]), verbo([target]), complemento([for, 'BCa', treatment])]). relacion([sujeto(['Our', ability, to, 'diagnose,', treat, and]), verbo([prevent]), complemento([defects, relies, on, our, understanding, of, this, variability])]). relacion([sujeto(['Mutation', of, the, transcription, factor, 'GATA3', in, humans]), verbo([causes]), complemento([the, highly, variable, 'hypoparathyroidism,', sensorineural, deafness, and, renal, dysplasia, '(', 'HDR)', syndrome])]). relacion([sujeto(['Because', mutation, of, the, homologous, cysteine]), verbo([causes]), complemento(['HDR', in, 'humans,', these, zebrafish, mutants, could, be, a, quick, and, effective, animal, model, for, understanding, the, role, of, gata3, in, the, 'HDR', disease, spectrum])]). relacion([sujeto(['We', demonstrate, 'that,', 'unexpectedly,', the, chaperone, proteins, 'Ahsa1', and, 'Hsp90']), verbo([promote]), complemento([severe, craniofacial, phenotypes, in, our, zebrafish, model, of, 'HDR', syndrome])]). relacion([sujeto(['However,', whether, 'GATA-3']), verbo([regulates]), complemento([the, function, of, mature, 'T', cells, beyond, 'TH2', determination, remains, poorly, understood])]). relacion([sujeto(['We']), verbo([found]), complemento([that, signaling, via, the, 'T', cell, antigen, receptor, '(', 'TCR)', and, cytokine, stimulation, promoted, 'GATA-3', expression, in, 'CD8(+)', 'T', 'cells,', which, controlled, cell, proliferation])]). relacion([sujeto(['The', 'proto-oncoprotein', 'c-Myc', was, a, critical]), verbo([target]), complemento([of, 'GATA-3', in, promoting, 'T', cell, proliferation])]). relacion([sujeto(['Our', study, thus, demonstrates, an, essential, role, for, 'GATA-3', in, controlling, the, maintenance, and, proliferation, of, 'T', cells, and]), verbo([provides]), complemento([insight, into, immunoregulation])]). relacion([sujeto(['After', four, weeks, of, oral, 'supplementation,', andrographolide, significantly]), verbo([inhibited]), complemento(['insulitis,', delayed, the, 'onset,', and, suppressed, the, development, of, diabetes, in, 30, -, 'week-old', 'NOD', mice, in, a, dose, dependent, manner])]). relacion([sujeto(['This', protective, status, was, correlated, with, a, substantially]), verbo([decreased]), complemento([production, of, interferon, '(', 'IFN)-γ', and, interleukin, '(', 'IL)-2,', increased, 'IL-10', and, transforming, growth, factor, '(', 'TGF)-β,', and, a, reduced, 'IL-17'])]). relacion([sujeto(['Andrographolide', also]), verbo([increased]), complemento(['GATA3', mRNA, expression, but, decreased, 'T-bet', and, 'RORγt', mRNA, expressions])]). relacion([sujeto(['Our', results]), verbo([suggested]), complemento([that, andrographolide, prevented, type, 1, diabetes, by, maintaining, 'Th1/Th2/Th17', homeostasis])]). relacion([sujeto(['Finally,', three, innate, immune, pathways, '(', complement, 'signaling,', 'toll-receptors', and, scavenger, and, 'immunoglobulins)', were, significantly]), verbo([associated]), complemento([with, 'GMT'])]). relacion([sujeto(['Expression', activity, for, the, genes, that]), verbo([regulate]), complemento([cellular, 'proliferation,', 'adhesion,', differentiation, and, inflammation, can, explain, a, significant, proportion, of, individual, variability, in, cortical, 'GMT'])]). relacion([sujeto(['Our', findings]), verbo([suggest]), complemento([that, normal, cerebral, aging, is, the, product, of, a, progressive, decline, in, regenerative, capacity, and, increased, neuroinflammation])]). relacion([sujeto(['The', reprogramming, factors, that]), verbo([induce]), complemento([pluripotency, have, been, identified, primarily, from, embryonic, stem, cell, '(', 'ESC)-enriched,', 'pluripotency-associated', factors])]). relacion([sujeto(['Here,', we]), verbo([report]), complemento(['that,', during, mouse, somatic, cell, 'reprogramming,', pluripotency, can, be, induced, with, lineage, specifiers, that, are, pluripotency, rivals, to, suppress, 'ESC', 'identity,', most, of, which, are, not, enriched, in, 'ESCs'])]). relacion([sujeto(['We']), verbo([found]), complemento([that, 'OCT4', and, 'SOX2,', the, core, regulators, of, 'pluripotency,', can, be, replaced, by, lineage, specifiers, that, are, involved, in, mesendodermal, '(', 'ME)', specification, and, in, ectodermal, '(', 'ECT)', 'specification,', respectively])]). relacion([sujeto(['Surprisingly,', the, two, counteracting, lineage, specifiers, can, synergistically]), verbo([induce]), complemento([pluripotency, in, the, absence, of, both, 'OCT4', and, 'SOX2'])]). relacion([sujeto(['Our', study]), verbo([suggests]), complemento([a, &, 'quot;seesaw', 'model"', in, which, a, balance, that, is, established, using, pluripotency, factors, 'and/or', counteracting, lineage, specifiers, can, facilitate, reprogramming])]). relacion([sujeto(['The', present, study, aimed, to, investigate, the, role, of, the, 'GATA']), verbo([binding]), complemento(['protein 3', '(', 'GATA‑3)/interleukin', '(', 'IL)‑5', signaling, pathway, in, 'IPD‑induced', inhibition, of, asthma])]). relacion([sujeto(['The', results, revealed, that, sensitization, by, 'OVA', significantly]), verbo([increased]), complemento([airway, resistance, and, the, percentage, of, 'EOS', in, peripheral, blood, and, induced, significant, inflammatory, changes, in, lung, 'tissue,', as, demonstrated, by, thick, 'epithelium,', goblet, cell, hyperplasia, and, submucosal, cell, infiltration])]). relacion([sujeto(['In', 'addition,', sensitization, by, 'OVA', was]), verbo([found]), complemento([to, markedly, upregulate, 'IL‑5', mRNA, and, protein, expression])]). relacion([sujeto(['Airway', resistance, was]), verbo([found]), complemento([to, positively, correlate, with, the, expression, of, 'IL‑5', in, the, rat, lung, tissues])]). relacion([sujeto(['Sensitization', by, 'OVA', was, also, observed, to, markedly]), verbo([enhance]), complemento(['GATA‑3', protein, expression, and, 'GATA‑3', levels, were, found, to, positively, correlate, with, airway, resistance, and, 'IL‑5', levels])]). relacion([sujeto(['Similar', to, the, effect, of, 'BUD,', treatment, with, 'C‑IPD', or, 'L‑IPD', was]), verbo([found]), complemento([to, significantly, attenuate, 'OVA‑induced', increases, in, airway, resistance, and, the, percentage, of, 'EOS', in, peripheral, blood])]). relacion([sujeto(['In', the, present, 'study,', 'IPD', intervention, was, demonstrated, to, ameliorate, airway, hyperreactivity, and, inflammation, and, the, mechanisms, may]), verbo([involve]), complemento([inhibition, of, the, 'GATA‑3/IL‑5', signaling, pathway])]). relacion([sujeto(['Splenocytes', of, immunized, mice, were]), verbo([stimulated]), complemento([in, vitro, and, then, proliferation, 'responses,', cytokine, secretion, and, mRNA, expression, of, genes, involved, in, immunotherapy, were, examined, by, 'ELISA', and, 'real-time', 'PCR'])]). relacion([sujeto(['Immunotherapy', with, the, rHM]), verbo([induced]), complemento([the, highest, ratio, of, the, 'IgG2a/IgG1', levels, compared, to, allergenic, cocktail, or, 'C'])]). relacion([sujeto(['The', rHM, was, able, to]), verbo([induce]), complemento([proliferative, responses, as, well, as, the, allergenic, cocktail, in, cultured, splenocytes])]). relacion([sujeto(['Interestingly,', mRNA, expression, of, 'GATA3', was, strongly]), verbo([decreased]), complemento([in, 'rHM-treated', mice, whereas, mRNA, expression, of, 'T-bet', and, 'Foxp3', was, significantly, increased])]). relacion([sujeto(['Using', 'gain-', and, 'loss-of-function', approaches, together, with, a, synthetic, 'Zinc-finger', polypeptide, '(', 6, 'ZFP)', engineered, to]), verbo([prevent]), complemento([transcription, factor, binding, to, a, defined, cis, 'element,', we, show, that, the, transcription, factor, 'EBF1', promotes, 'B cell', lineage, commitment, by, directly, repressing, expression, of, the, 'T-cell-lineage-requisite', 'Gata3', gene])]). relacion([sujeto(['Ebf1-deficient', lymphoid, progenitors, exhibited]), verbo([increased]), complemento(['T cell', lineage, potential, and, elevated, 'Gata3', transcript, 'expression,', whereas, enforced, 'EBF1', expression, inhibited, 'T cell', differentiation, and, caused, rapid, loss, of, 'Gata3', mRNA])]). relacion([sujeto(['Notably,', 6, 'ZFP-mediated', perturbation, of, 'EBF1']), verbo([binding]), complemento([to, a, 'Gata3', regulatory, region, restored, 'Gata3', 'expression,', abrogated, 'EBF1-driven', suppression, of, 'T cell', 'differentiation,', and, prevented, 'B', cell, differentiation, via, a, 'GATA3-dependent', mechanism])]). relacion([sujeto(['Furthermore,', 'EBF1']), verbo([binding]), complemento([to, 'Gata3', regulatory, sites, induced, repressive, histone, modifications, across, this, region])]). relacion([sujeto(['During', blastocyst, 'formation,', the, relative, levels, of, 'EED', and, 'KDM6B', expression, determine, altered, polycomb, repressor, 2, '(', 'PRC2)', complex, recruitment, and, incorporation, of, the, repressive, histone, 'H3', lysine, 27, trimethylation, '(', 'H3K27Me3)', mark, at, the, chromatin, domains, of, 'TE-specific', master, regulators, 'CDX2', and, 'GATA3,']), verbo([leading]), complemento([to, their, activation, in, the, 'TE', lineage, and, repression, in, the, 'ICM', lineage])]). relacion([sujeto(['Furthermore,', ectopic]), verbo([gain]), complemento([of, 'EED', along, with, depletion, of, 'KDM6B', in, preimplantation, mouse, embryos, abrogates, 'CDX2', and, 'GATA3', expression, in, the, nascent, 'TE', lineage])]). relacion([sujeto(['The']), verbo([loss]), complemento([of, 'CDX2', and, 'GATA3', in, the, nascent, 'TE', lineage, results, in, improper, 'TE', 'development,', leading, to, failure, in, embryo, implantation, to, the, uterus])]). relacion([sujeto([&, 'nbsp;difficile-infected', mice]), verbo([expressed]), complemento([similar, levels, of, 'CD69', and, 'CD25'])]). relacion([sujeto(['The', caeca, and, colons, of, the, infected, mice, showed, a, significant]), verbo([increase]), complemento([in, eukaryotic, initiation, factor, 2, α, '(', 'eIF2α)', 'phosphorylation,', but, neither, the, splicing, of, 'Xbp1', nor, the, 'up-regulation', of, endoplasmic, reticulum, 'chaperones,', casting, doubt, on, the, 'full-fledged', induction, of, the, unfolded, protein, response, by, 'C'])]). relacion([sujeto(['At', the, precursor, stage, of, naive, 'CD4', 'T', 'cells,', transcriptional, mechanisms]), verbo([maintain]), complemento([the, potential, and, in, the, meantime, prevent, spontaneous, differentiation, to, 'Th2', fate])]). relacion([sujeto(['Upon', 'T-cell', receptor, '(', 'TCR)', 'engagement,', naive, 'CD4', 'T', cells, are]), verbo([induced]), complemento([by, polarizing, signals, of, the, 'interleukin-4/Stat6', and, 'Jagged/Notch', pathways, to, 'up-regulate', the, expression, of, 'GATA-3'])]). relacion([sujeto(['Once', 'up-regulated,', 'GATA-3', drives, 'Th2', and]), verbo([suppresses]), complemento(['Th1', differentiation, in, a, cell, autonomous, fashion])]). relacion([sujeto(['Once', 'differentiated,', 'Th2', effector, cells, promptly, produce, 'Th2', cytokines, upon, 'TCR', 'stimulation,', which, is]), verbo([regulated]), complemento([by, concerted, actions, of, 'GATA-3,', 'TCR', 'signalling,', enhancers, and, the, 'Th2', locus, control, region])]). relacion([sujeto(['This', review]), verbo([provides]), complemento([a, detailed, account, of, the, transcriptional, regulatory, events, at, these, different, stages, of, 'Th2', differentiation])]). relacion([sujeto(['Although', genetic, mapping, and, subsequent, functional, studies, indicate, that, 'GATA3', 'haplo-insufficiency']), verbo([causes]), complemento([human, 'HDR', 'syndrome,', the, role, of, 'Gata3', in, sensorineural, deafness, and, auditory, system, development, is, largely, unknown])]). relacion([sujeto(['In', this, 'study,', we, show, that, 'Gata3', is, continuously]), verbo([expressed]), complemento([in, the, developing, mouse, inner, ear])]). relacion([sujeto(['Loss', of, 'Gata3', function]), verbo([leads]), complemento([to, the, failure, in, the, specification, of, prosensory, domain, and, 'subsequently,', to, increased, cell, death, in, the, cochlear, duct])]). relacion([sujeto(['Our', results, demonstrate, the, essential, role, of, 'Gata3', in, specifying, the, prosensory, domain, in, the, cochlea, and, in]), verbo([regulating]), complemento([the, survival, of, 'SGNs,', thus, identifying, a, molecular, mechanism, underlying, human, 'HDR', syndrome])]). relacion([sujeto(['Tubular', adenomas, in, the, urinary, tract, with, the, same, appearance, as, those, in, the, gastrointestinal, tract]), verbo([have]), complemento([not, yet, been, described, in, the, literature])]). relacion([sujeto(['We', herein]), verbo([report]), complemento([4, cases, of, tubular, adenomas, in, the, urinary, tract, encountered, within, our, consult, practice])]). relacion([sujeto(['One', lesion, was, large, measuring, 1.4, cm]), verbo([associated]), complemento([with, pseudoinvasion, as, well, as, invasive, adenocarcinoma])]). relacion([sujeto(['One', case, showed, positive]), verbo([nuclear]), complemento(['β-catenin', staining])]). relacion([sujeto(['Tubular', adenoma, of, the, urinary, tract, is, a, rare, 'lesion,', and, recognition, of, this, entity, will, encourage, further]), verbo([reports]), complemento([and, help, to, better, understand, the, relation, of, tubular, adenoma, to, concurrent, and, subsequent, urinary, tract, malignancies])]). relacion([sujeto(['Etiologic', diagnosis, of, seizure]), verbo([requires]), complemento([proper, consideration, of, apparently, unrelated, clinical, features, of, the, patient])]). relacion([sujeto(['Here,', we]), verbo([report]), complemento([the, case, of, a, patient, of, status, epilepticus, with, 'moderate-to-severe', bilateral, sensorineural, deafness])]). relacion([sujeto(['The', features, were, consistent, with, 'Barakat', 'syndrome,', a, rare, developmental, disorder]), verbo([associated]), complemento([with, mutations, in, the, 'GATA3', gene])]). relacion([sujeto(['To', the, best, of, our, 'knowledge,', this, is, the, first]), verbo([reported]), complemento([case, of, 'Barakat', syndrome, from, 'India'])]). relacion([sujeto(['Mice', homozygous, for, the, juvenile, alopecia, mutation, '(', 'jal)', display, patches, of, hair]), verbo([loss]), complemento([that, appear, as, soon, as, hair, develops, in, the, neonatal, period, and, persist, throughout, life])]). relacion([sujeto(['Although', a]), verbo([report]), complemento([initially, describing, this, mouse, variant, suggested, that, jal, maps, to, mouse, 'Chromosome', 13, ',', our, preliminary, mapping, analysis, did, not, support, that, claim])]). relacion([sujeto(['Only', markers, from, the, centromeric, tip, of, 'Chromosome', 2, failed, to, segregate, independently, from, 'jal,']), verbo([suggesting]), complemento([that, jal, resides, in, that, region])]). relacion([sujeto(['This', analysis, restricted, 'jal\'s', position, between, 'D2Mit359', and, 'D2Mit80,', an, interval, that, includes, 'Il2ra', '(', for, interleukin, 2, 'receptor,', alpha, 'chain),', a, gene, that, is, known, to, be]), verbo([associated]), complemento([with, alopecia, areata, in, humans])]). relacion([sujeto(['This', span, includes, ten, 'genes-only', one, of, 'which,', 'Gata3', '(', for, 'GATA']), verbo([binding]), complemento([protein, 3, ')', -, is, known, to, be, expressed, in, skin])]). relacion([sujeto(['We', therefore, recommend, that, the, jal, designation, be, changed, to, 'Gata3jal,', and]), verbo([suggest]), complemento([that, this, mouse, variant, may, provide, an, animal, model, for, at, least, some, forms, of, focal, alopecia, that, have, their, primary, defect, in, the, hair, follicle, and, lack, an, inflammatory, component])]). relacion([sujeto(['ERα', is, a, member, of, the]), verbo([nuclear]), complemento([receptor, superfamily, of, transcription, factors, and, regulates, target, gene, expression, in, a, 'ligand-dependent', manner])]). relacion([sujeto(['It']), verbo([has]), complemento([also, been, shown, to, interact, with, 'G-protein', coupled, receptors, and, associated, signaling, molecules, in, the, cytoplasm])]). relacion([sujeto(['Transcriptionally,', 'ERα', either]), verbo([binds]), complemento(['DNA', directly, through, conserved, estrogen, response, element, sequence, motifs, or, indirectly, by, tethering, to, other, interacting, transcription, factors, and, nucleate, transcriptional, regulatory, complexes, which, include, an, array, of, 'co-regulator', proteins])]). relacion([sujeto(['Genome-scale', studies, of, 'ERα', transcriptional, activity, and, localization]), verbo([have]), complemento([revealed, mechanistic, complexity, and, insights, including, novel, interactions, with, several, transcription, 'factors,', including, 'FOXA1,', 'AP-2g,', 'GATA3,', and, 'RUNX1,', which, function, as, 'pioneering,', 'collaborative,', or, tethering, factors])]). relacion([sujeto(['We', show, here, that, 'Islet-1']), verbo([acts]), complemento([genetically, downstream, of, 'Phox2B', in, cells, of, the, sympathoadrenal, cell, lineage, and, that, the, development, of, sympathetic, neurons, and, chromaffin, cells, is, impaired, in, mouse, embryos, with, a, conditional, deletion, of, 'Islet-1', controlled, by, the, wnt1, promotor])]). relacion([sujeto(['However,', our, data, indicate, that, the, subsequent, survival, of, sympathetic, neuron, precursors, and, their, differentiation, towards, 'TrkA']), verbo([expressing]), complemento([neurons, depends, on, 'Islet-1', function])]). relacion([sujeto(['Together', our, data, indicate, that, 'Islet-1', is, not, essentially]), verbo([required]), complemento([for, the, initial, differentiation, of, sympathoadrenal, 'cells,', but, has, an, important, function, for, the, correct, subsequent, development, of, sympathetic, neurons, and, chromaffin, cells])]). relacion([sujeto(['Around', late, 'gastrulation,', the, 'PPE', forms, at, the, border, surrounding, the, anterior, neural, 'plate,', and]), verbo([expresses]), complemento([a, unique, set, of, evolutionarily, conserved, transcription, regulators, including, 'Six1,', 'Eya', 1, and, 'Eya2'])]). relacion([sujeto(['Here,', we, describe, the, first]), verbo([report]), complemento([to, generate, and, characterize, the, 'SIX1(+)', 'PPE', cells, from, human, embryonic, stem, '(', 'ES)', cells, by, adherent, differentiation])]). relacion([sujeto(['Before', forming, 'PPE', 'cells,', differentiating, cultures, first]), verbo([expressed]), complemento([the, 'non-neural', ectoderm, specific, transcriptional, factors, 'TFAP2A,', 'GATA2,', 'GATA3,', 'DLX3,', and, 'DLX5,', which, are, crucial, in, establishing, the, 'PPE', competence])]). relacion([sujeto(['We', demonstrated, that, bone, morphogenetic, protein, '(', 'BMP)', activity, plays, a, transient, but, essential, role, in]), verbo([inducing]), complemento([expression, of, these, 'PPE', competence, factors, and, eventually, the, 'PPE', cells])]). relacion([sujeto(['Interestingly,', we]), verbo([found]), complemento([that, attenuating, 'BMP', signaling, after, establishing, the, competence, state, induces, anterior, placode, precursors])]). relacion([sujeto([is, widely, used, for, spice, and, flavoring, for, 'foods,', and]), verbo([has]), complemento([been, reported, to, have, 'anti-inflammatory', activity])]). relacion([sujeto(['Fungal', protease, mixed, with, chicken, egg, ovalbumin, allergen, was, used, as, a, challenge, to]), verbo([induce]), complemento([murine, experimental, asthma])]). relacion([sujeto(['Additionally,', activation, of, the, 'T', helper, type, 2, '(', 'Th2)', 'cell-specific', master, transcription, 'factor,', 'GATA3', was]), verbo([decreased]), complemento([with, macelignan, treatment])]). relacion([sujeto(['Our', data, show, that, macelignan]), verbo([has]), complemento(['anti-inflammatory', effects, on, 'Th2', 'cell-mediated', allergic, lung, inflammation, and, could, potentially, provide, a, novel, preventative, 'and/or', therapy, for, the, treatment, of, allergic, diseases])]). relacion([sujeto(['tb)', is, a, challenging, for]), verbo([preventing]), complemento(['TB', infection])]). relacion([sujeto(['The', results, showed, that, the, immunized, mice, remarkably, elicited]), verbo([enhanced]), complemento(['T', cell, responses, and, protection, against, 'M'])]). relacion([sujeto(['These', findings, indicate, that, the, 'nano-chitosan', can, significantly, elevate, the, immunologic, and, protective, effects, of, the, 'DNA', 'vaccine,', and, the, 'nano-Esat-6/3e-FL', is, a, useful, vaccine, for]), verbo([preventing]), complemento(['M'])]). relacion([sujeto(['Numbers', of, 'CD8(+)IL-13(+)', 'T', cells, are]), verbo([increased]), complemento([in, asthmatics, and, during, the, development, of, experimental, asthma, in, mice])]). relacion([sujeto(['In', an, atopic, environment, rich, in, 'IL-4,', these, 'CD8(+)', 'T', cells]), verbo([mediate]), complemento([asthmatic, 'responses,', but, the, mechanisms, regulating, the, conversion, of, 'CD8(+)', effector, 'T', cells, from, 'IFN-γ-', to, pathogenic, 'IL-13-producing', effector, cells, that, contribute, to, an, asthma, phenotype, have, not, been, defined])]). relacion([sujeto(['Expression', of, the, 'gene,', 'protein,', and, enzymatic, activity, of, 'Cyp11a1', were, markedly]), verbo([increased]), complemento([in, 'CD8(+)', 'T', cells, differentiated, in, the, presence, of, 'IL-2', plus, 'IL-4', compared, with, cells, differentiated, in, 'IL-2', alone])]). relacion([sujeto(['Inhibition', of, 'Cyp11a1', enzymatic, activity, with, aminoglutethimide, or, reduction, in, the, expression, of, 'Cyp11a1', using, short, hairpin, 'RNA']), verbo([prevented]), complemento([the, 'IL-4-induced', conversion, of, 'IFN-γ-', to, 'IL-13-producing', cells, without, affecting, expression, of, the, 'lineage-specific', transcription, factors, 'T-box', expressed, in, 'T', cells, '(', 'T-bet)', or, 'GATA', binding, protein, 3, '(', 'GATA3)'])]). relacion([sujeto(['Loss', of, several, genes, will, disrupt, ear, morphogenesis, or]), verbo([arrest]), complemento([of, neurosensory, epithelia, development])]). relacion([sujeto(['We', previously, showed, in, null, mutants, that, the]), verbo([loss]), complemento([of, the, transcription, 'factor,', 'Gata3,', results, specifically, in, the, loss, of, all, cochlear, neurosensory, development])]). relacion([sujeto(['To', better, understand, the, stage, specific, effects, of, 'Gata3,', we, investigated, the, role, of, 'Gata3', in, cochlear, neurosensory, specification, and, differentiation, utilizing, a, 'LoxP']), verbo([targeted]), complemento(['Gata3', line, and, two, 'Cre', lines])]). relacion([sujeto(['Our', conditional, deletion, studies]), verbo([reveal]), complemento([a, major, role, of, 'Gata3', in, the, signaling, of, prosensory, genes, and, in, the, differentiation, of, cochlear, neurosenory, cells])]). relacion([sujeto(['We']), verbo([suggest]), complemento([that, 'Gata3', may, act, in, combination, with, 'Eya1,', 'Six1,', and, 'Sox2', in, cochlear, prosensory, gene, signaling])]). relacion([sujeto(['Progression', to, persistent, asthma, is]), verbo([associated]), complemento([with, a, 'Th2-biased', immunological, response, and, structural, remodelling, of, the, airways])]). relacion([sujeto(['The', underlying, mechanisms, are, 'unclear,', but, could]), verbo([involve]), complemento([epigenetic, changes])]). relacion([sujeto(['To', investigate, 'this,', we, employed, a, recently, developed, mouse, model, in, which, 'self-limited', neonatal, infection, with, a, 'pneumovirus,', followed, by, sensitisation, to, ovalbumin, via, the, respiratory, tract, and, 'low-level', chronic, challenge, with, aerosolised, 'antigen,']), verbo([leads]), complemento([to, development, of, an, asthmatic, phenotype])]). relacion([sujeto(['We', assessed, expression, of, microRNA, by, cells, in, the, proximal, 'airways,', comparing, changes, over, the, period, of, disease, 'progression,', and, used]), verbo([target]), complemento([prediction, databases, to, identify, genes, likely, to, be, 'up-', or, downregulated, as, a, consequence, of, altered, regulation, of, microRNA])]). relacion([sujeto(['We']), verbo([found]), complemento([that, a, limited, number, of, microRNAs, exhibited, marked, 'up-', or, downregulation, following, 'early-life', infection, and, 'sensitisation,', for, many, of, which, the, levels, of, expression, were, further, changed, following, chronic, challenge, with, the, sensitizing, antigen])]). relacion([sujeto(['Targets', of, these, microRNAs, included, genes]), verbo([involved]), complemento([in, immune, or, inflammatory, responses, '(', e])]). relacion([sujeto(['In', pulmonary, 'CD4(+)', 'T', 'cells,', there, was, significant, demethylation, at, promoter, sites, for, 'interleukin-4', and, 'interferon-γ,', the, latter]), verbo([increasing]), complemento([following, chronic, challenge])]). relacion([sujeto(['We', conclude, 'that,', in, this, 'model,', progression, to, an, asthmatic, phenotype, is, linked, to, epigenetic, regulation, of, genes]), verbo([associated]), complemento([with, inflammation, and, structural, 'remodelling,', and, with, 'T-cell', commitment, to, a, 'Th2', immunological, response])]). relacion([sujeto(['Epigenetic', changes]), verbo([associated]), complemento([with, this, pattern, of, gene, activation, might, play, a, role, in, the, development, of, childhood, asthma])]). relacion([sujeto(['GATA3', is, a, zinc, finger, transcription, factor, that]), verbo([regulates]), complemento([the, normal, development, of, many, tissues, and, cell, types])]). relacion([sujeto(['Recent', studies]), verbo([have]), complemento([shown, that, immunohistochemical, nuclear, staining, for, 'GATA3', among, tumors, is, highly, restricted, to, carcinomas, of, breast, and, urothelial, 'origin;', however, salivary, gland, tumors, have, not, been, tested])]). relacion([sujeto(['Rather,', it, is]), verbo([expressed]), complemento([across, many, different, types, of, salivary, gland, neoplasms])]). relacion([sujeto(['Although', 'GATA3', immunohistochemistry, is, not, helpful, in, resolving, the, differential, diagnosis, between, a, primary, salivary, gland, neoplasm, and, metastatic, breast, 'cancer,', it, may]), verbo([have]), complemento([some, utility, in, subtyping, salivary, gland, 'tumors,', particularly, salivary, duct, carcinoma, and, mammary, analogue, secretory, carcinoma])]). relacion([sujeto(['GATA3', is, a, 'zinc-finger', transcription, 'factor,', which, is]), verbo([expressed]), complemento([in, various, normal, and, neoplastic, tissues])]). relacion([sujeto(['Few', studies]), verbo([have]), complemento([investigated, its, positivity, in, various, neoplasms, that, may, mimic, urothelial, neoplasms])]). relacion([sujeto(['Recognition', of, this]), verbo([finding]), complemento([will, aid, pathologists, in, preventing, a, misdiagnosis, of, a, urothelial, tumor, based, on, 'GATA3', 'expression,', which, is, critical, given, the, differences, in, 'treatment,', 'follow-up', and, prognosis, between, bladder, paragangliomas, and, urothelial, carcinoma])]). relacion([sujeto(['Spleen', deficiency, could]), verbo([lead]), complemento([to, increase, expression, of, 'JAK1,', 'STAT1', and, 'Interleukin', 4, '(', 'IL-4)', in, the, 'brain,', but, the, decrease, expression, of, 'Suppressor', of, cytokine, signaling, 1, '(', 'SOCS1),', prolactin, receptor, '(', 'PRLR)', and, binding, protein, 3, '(', 'GATA', 3, ')'])]). relacion([sujeto(['Sijunzi', decoction, could]), verbo([increase]), complemento([expression, of, 'STAT3,', 'Prolactin', '(', 'PRL)', and, 'GATA3,', but, decrease, expression, of, 'JAK1,', 'STAT,', 'STAT4,', 'Interleukin', 10, 'receptor,', alpha, '(', 'IL10RA),', 'Coagulation', factor, 'II', '(', 'F2),', 'PRLR,', 'MAD', homolog, 3, '(', 'SMAD3)', and, 'IL-4'])]). relacion([sujeto(['Yupingfeng', powder, could]), verbo([decrease]), complemento([expression, of, 'JAK1,', 'STAT1,', 'STAT4,', 'SOCS4_', 'predicted,', 'Epidermal', growth, factor, receptor, '(', 'EGFR),', 'PRLR,', 'High', mobility, group, 'AT-hook', 1, '(', 'HMGA10),', 'IL-4'])]). relacion([sujeto(['Transforming', growth, factor, '(', 'ß1TGFß1)', can]), verbo([promote]), complemento([proliferation, in, late, stage, cancers, but, acts, as, a, tumor, suppressor, in, normal, epithelial, cells, and, in, early, stage, cancers])]). relacion([sujeto(['Although,', the, 'TGFß', pathway]), verbo([has]), complemento([been, shown, to, play, a, key, role, in, tumorigenesis, and, 'metastasis,', only, a, limited, number, of, models, have, been, developed, to, understand, this, process])]). relacion([sujeto(['The', 'MB-231', 'triple-negative', breast, cancer, cell, line]), verbo([has]), complemento([been, extensively, characterized, and, has, been, shown, to, continue, to, proliferate, and, undergo, 'epithelial-to-mesenchymal', transition, '(', 'EMT)', upon, 'TGFß1', stimulation])]). relacion([sujeto(['We']), verbo([have]), complemento([previously, shown, by, microarray, analysis, that, expression, of, 'GATA3', in, 'MB-231', cells, results, in, reprogramming, of, these, cells, from, a, basal, to, a, luminal, subtype, associated, with, a, reduction, of, metastasis, and, tumorigenesis, when, implanted, as, xenografts])]). relacion([sujeto(['Furthermore,', our, microarray, analysis, revealed, a, significant]), verbo([increase]), complemento([of, 'BMP5', in, 231, -, 'GATA3', cells])]). relacion([sujeto(['Thus,', this, model, offers, a, means, to, further, investigate, potentially, novel, mechanisms]), verbo([involved]), complemento([in, the, switch, in, response, to, 'TGFß1', from, tumor, promoter, to, tumor, suppressor, through, the, reprogramming, of, a, 'triple-negative', breast, cancer, cell, line, by, the, 'GATA3', transcription, factor])]). relacion([sujeto(['We']), verbo([have]), complemento([recently, described, the, presence, of, the, erythropoietin, receptor, '(', 'EPO-R)', on, 'CD4(+)', lymphocytes, and, demonstrated, that, its, expression, increases, during, their, 'activation,', reaching, a, level, reported, to, be, typical, for, erythroid, progenitors])]). relacion([sujeto(['This', observation]), verbo([suggests]), complemento([that, 'EPO-R', expression, is, modulated, during, lymphocyte, 'activation,', which, may, be, important, for, the, 'cells\'', function])]). relacion([sujeto(['Here', we, investigated, whether, the, expression, of, 'GATA1,', 'GATA3', and, 'Sp1', transcription, factors, is, correlated, with, the, expression, of, 'EPO-R', in, human, 'CD4(+)', lymphocytes]), verbo([stimulated]), complemento([with, monoclonal, 'anti-CD3', antibody])]). relacion([sujeto(['However,', stimulation, resulted, in, the, significantly]), verbo([increased]), complemento([expression, of, the, 'Sp1', factor])]). relacion([sujeto(['CD4(+)', lymphocytes]), verbo([stimulated]), complemento([with, 'anti-CD3', antibody, exhibited, an, increase, in, both, the, expression, level, of, 'EPOR', gene, and, the, number, of, 'EPO-R', molecules, on, the, 'cells\'', 'surface,', the, latter, being, significantly, correlated, with, the, increased, expression, of, 'Sp1'])]). relacion([sujeto(['It', seems, that, 'Sp1', may, significantly, affect, the, number, of, 'EPO-R', molecules, present, on, the, surface, of]), verbo([activated]), complemento(['CD4(+)', lymphocytes])]). relacion([sujeto(['The', innate, lymphoid, cell, '(', 'ILC)', family]), verbo([has]), complemento([recently, expanded, with, the, discovery, of, 'type-2', innate, lymphoid, cells, '(', 'ILC2)'])]). relacion([sujeto(['These', cells, are, critical, components, of, the, innate, immune, response, to, parasitic, worm, infections, and]), verbo([have]), complemento([also, been, implicated, in, the, pathogenesis, of, asthma, and, allergy])]). relacion([sujeto(['The', role, of, 'Th17', cells, and]), verbo([associated]), complemento([cytokines, was, investigated, in, oral, lichen, planus])]). relacion([sujeto(['Results', showed, that, 'Th17-type', and, 'Th0-type', 'molecules\'', 'mRNAs,', when, compared, with, results, obtained, from, tissue, 'controls,', were]), verbo([increased]), complemento([in, biopsies, of, erosive, 'lesions,', whereas, 'Th2-type', 'molecules\'', mRNAs, were, increased, in, reticular, lesions])]). relacion([sujeto(['When', the, 'CD4+', 'T-cell', 'clones,', derived, from, oral, lichen, planus, tissues, and, tissue, 'controls,', were, 'analyzed,', a, higher, prevalence, of, 'Th17', '(', confirmed, by, an]), verbo([increased]), complemento(['CD161', 'expression)', and, 'Th0', 'CD4+', 'T', clones, was, found, in, erosive, 'lesions,', whereas, a, prevalence, of, 'Th2', clones, was, observed, in, reticular, lesions])]). relacion([sujeto(['Our', data]), verbo([suggest]), complemento([that, 'Th17,', 'Th0,', and, 'Th2', 'cells,', 'respectively,', may, have, a, role, in, the, pathogenesis, of, erosive, and, reticular, oral, lichen, planus])]). relacion([sujeto(['Patients', with, 'triple-negative', breast, cancer, '(', 'TNBC)', and, residual, disease, after, neoadjuvant, chemotherapy, generally]), verbo([have]), complemento([worse, 'outcome;', 'however,', some, patients, with, residual, tumor, after, neoadjuvant, chemotherapy, do, not, relapse])]). relacion([sujeto(['The', 'TNBC', subgroup, that, predicted, to]), verbo([have]), complemento([relatively, favorable, prognosis, was, characterized, by, high, expression, of, &, 'quot;luminal-like"', genes, '[', 'androgen-receptor', '(', 'AR)', and, 'GATA3],', whereas, the, subgroup, with, worse, prognosis, was, characterized, by, expression, of, cancer, 'stem-cell', markers])]). relacion([sujeto(['For', these, 'women,', new, therapeutic, strategies, like]), verbo([targeting]), complemento(['AR', activation, or, cancer, stem, cells, may, need, to, be, developed])]). relacion([sujeto(['The', strongest, signal, maps, to, a, transcriptional, enhancer, element, in, which, the, 'G', allele, of, the, best, candidate, causative, variant, rs554219]), verbo([increases]), complemento([risk, of, breast, 'cancer,', reduces, both, binding, of, 'ELK4', transcription, factor, and, luciferase, activity, in, reporter, 'assays,', and, may, be, associated, with, low, cyclin, 'D1', protein, levels, in, tumors])]). relacion([sujeto(['Risk', association, signal, 2, ',', 'rs75915166,', creates, a, 'GATA3']), verbo([binding]), complemento([site, within, a, silencer, element])]). relacion([sujeto(['Chromatin', conformation, studies, demonstrate, that, these, enhancer, and, silencer, elements]), verbo([interact]), complemento([with, each, other, and, with, their, likely, target, 'gene,', 'CCND1'])]). relacion([sujeto(['By', 'Masson', 'staining,', the, liver, sections, from, the, corilagin, group, showed, less, collagen, distributed, around, 'granulomas,']), verbo([decreased]), complemento([liver, fibrosis, in, the, portal, tracts, and, less, formed, interlobular, tissue])]). relacion([sujeto(['In', 'conclusion,', corilagin, extraction, can]), verbo([decrease]), complemento([the, level, of, 'Th2-associated', profibrotic, cytokine, 'IL-13,', and, 'down-regulate', the, transcription, of, 'GATA3', mRNA, in, spleen, 'cells,', which, alleviate, the, hepatic, fibrosis, caused, by, egg, granuloma, in, 'Schistosoma', japonicum, infection])]). relacion([sujeto(['High-throughput', screening]), verbo([has]), complemento([uncovered, many, compounds, that, are, effective, at, pharmacologically, restoring, 'BRM', and, thereby, inhibit, cancer, cell, growth])]). relacion([sujeto(['As', we, do, not, know, which, specific, 'proteins,', if, 'any,']), verbo([regulate]), complemento(['BRM,', we, sought, to, identify, the, 'proteins,', which, underlie, the, epigenetic, suppression, of, 'BRM'])]). relacion([sujeto(['By', selectively, knocking, down, each, 'HDAC,', we]), verbo([found]), complemento([that, 'HDAC3', and, 'HDAC9', regulate, 'BRM', 'expression,', whereas, 'HDAC2', controls, its, acetylation])]). relacion([sujeto(['Similarly,', we, ectopically, overexpressed, 21, different, histone, acetyltransferases, and]), verbo([found]), complemento([that, 'KAT6A,', 'KAT6B', and, 'KAT7', induce, 'BRM', 'expression,', whereas, 'KAT2B', and, 'KAT8', induce, its, acetylation])]). relacion([sujeto(['Knockdown', of, either, 'GATA3', 'and/or', 'MEF2D', downregulated, 'HDAC9', and]), verbo([induced]), complemento(['BRM'])]). relacion([sujeto(['As']), verbo([targets]), complemento([for, molecular, biotherapy, are, typically, 'uniquely,', or, simply, differentially, expressed, in, cancer, 'cells,', we, also, determined, if, any, of, these, proteins, are, dysregulated])]). relacion([sujeto(['However,', by, 'sequencing,', no, mutations, were]), verbo([found]), complemento([in, any, of, these, 'BRM-regulating', 'HDACs,', 'HATs', or, 'TFs'])]). relacion([sujeto(['We', selectively, knocked, down, 'GATA3,', 'MEF2D,', 'HDAC3', and, 'HDAC9,', and]), verbo([found]), complemento([that, each, 'gene-specific', knockdown, induced, growth, inhibition])]). relacion([sujeto(['We', observed, that, both, 'GATA3', and, 'HDAC9', were, greatly, overexpressed, only, in, 'BRM-negative', cell, lines, indicating, that, 'HDAC9', may, be, a, good]), verbo([target]), complemento([for, therapy])]). relacion([sujeto(['We', also]), verbo([found]), complemento([that, the, 'mitogen-activated', protein, '(', 'MAP)', kinase, pathway, regulates, both, 'BRM', acetylation, and, 'BRM', silencing, as, 'MAP', kinase, pathway, inhibitors, both, induced, 'BRM', as, well, as, caused, 'BRM', deacetylation])]). relacion([sujeto(['In', 'vitro,', 'IL-4']), verbo([triggered]), complemento([the, stepwise, molecular, conversion, of, 'CD8(+)', 'T', cells, from, 'IFN-γ', to, 'IL-13', production])]). relacion([sujeto(['During', the, initial, 'stage,', 'IL-4']), verbo([suppressed]), complemento(['T-bet', and, induced, 'GATA3', 'expression,', characterized, by, enhanced, activating, histone, modifications, and, 'RNA', polymerase, 'II', '(', 'Pol', 'II)', recruitment, to, the, 'GATA3', locus])]). relacion([sujeto(['However,']), verbo([enhanced]), complemento(['IL-13', transcription, only, occurred, at, a, later, stage, after, 'TCR', 'stimulation,', indicating, that, 'IL-4-induced', 'GATA3', recruitment, poises, the, 'IL-13', locus, for, 'TCR-mediated', transcription])]). relacion([sujeto(['Thus,', both, in, vivo, and, in, 'vitro,', an, atopic, '(', 'IL-4)', environment, poises, 'CD8(+)', 'T', cells, via, stepwise, epigenetic, and, phenotypic, mechanisms, for, pathogenic, conversion, to, 'IL-13', 'production,', which, is, ultimately]), verbo([triggered]), complemento([via, an, 'allergen-mediated', 'TCR', stimulus])]). relacion([sujeto(['They', are, also]), verbo([involved]), complemento([in, 'immune-mediated', pathology])]). relacion([sujeto(['Among', these, 'cells,', 'IFN-γ-producing', 'T', cells, '(', 'TH1)', are]), verbo([recognized]), complemento([as, having, a, 'pro-atherogenic', role])]). relacion([sujeto(['Recently,', the, 'IL-17-producing', 'T', helper, lineage, of, cells, '(', 'TH17)']), verbo([has]), complemento([been, identified, in, atherosclerotic, lesions])]). relacion([sujeto(['They']), verbo([have]), complemento([been, linked, to, atheroma, development, through, the, production, of, 'pro-inflammatory', mediators, present, in, these, lesions])]). relacion([sujeto(['Furthermore,', 'IL-22', producing, 'TCD4(+)', cells, '(', 'TH22)']), verbo([have]), complemento([been, identified, in, the, atheromatous, 'environment,', but, their, presence, and, function, has, not, been, investigated])]). relacion([sujeto(['The', aim, of, this, study, was, to, analyze, the, immune, response]), verbo([mediated]), complemento([by, 'pro-inflammatory', subtypes, of, 'TCD4(+)', cells, in, atheromatous, lesions])]). relacion([sujeto(['In', vitro, stimulation, of, atheroma, cells]), verbo([induced]), complemento(['IL-17', and, 'IFN-γ', production])]). relacion([sujeto(['Our', results, showed, the, presence, of, distinct, 'TCD4(+)', cells, subsets, in, human, carotid, lesions, and]), verbo([suggest]), complemento([that, interactions, among, them, may, contribute, to, the, atheroma, progression, and, destabilization])]). relacion([sujeto(['GATA']), verbo([binding]), complemento([protein, 3, '(', 'Gata3)', is, a, 'GATA', family, transcription, factor, that, controls, differentiation, of, naïve, 'CD4', 'T', cells, into, 'T', helper, 2, '(', 'Th2)', cells])]). relacion([sujeto(['However,', it, is, unknown, how, 'Gata3', simultaneously]), verbo([activates]), complemento(['Th2-specific', genes, while, repressing, those, of, other, 'Th', lineages])]). relacion([sujeto(['Here', we, show, that, chromodomain, helicase, 'DNA-binding', protein, 4, '(', 'Chd4)', forms, a, complex, with, 'Gata3', in, 'Th2', cells, that, both]), verbo([activates]), complemento(['Th2', cytokine, transcription, and, represses, the, 'Th1', cytokine, 'IFN-γ'])]). relacion([sujeto(['Thus,', 'Gata3/Chd4', forms, functionally, distinct, 'complexes,', which]), verbo([mediate]), complemento([both, positive, and, negative, gene, regulation, to, facilitate, 'Th2', cell, differentiation])]). relacion([sujeto(['GATA', transcription, factor, family, members]), verbo([have]), complemento([been, found, to, involve, in, the, growth, and, differentiation, of, mammary, gland])]). relacion([sujeto(['Among', them, 'GATA-3', is, regarded, as, the, most, critical, regulator]), verbo([involving]), complemento([the, tumorigenesis, of, breast, cancer, '(', 'BC)'])]). relacion([sujeto(['Recently,', trichorhinophalangeal, 'syndrome-1', gene, '(', 'TRPS-1),', a, new, 'GATA', family, 'member,']), verbo([has]), complemento([been, identified, to, be, highly, prevalent, in, breast, cancer])]). relacion([sujeto(['Studies']), verbo([have]), complemento([shown, that, 'miR221/222', is, able, to, downregulate, the, expression, of, an, epithelial, cell, marker, 'E-cadherin', by, targeting, 'TRPS-1,', resulting, in, mammary, epithelial, cells, transition, to, mesenchymal, cell, '(', 'EMT)'])]). relacion([sujeto(['In', 'addition,', it]), verbo([has]), complemento([been, well, accepted, 'that,', and, the, 'Science', and, 'Technology', 'Bureau', of, 'Jiaxing', '(', 2012, 'AY1071-2)TRPS-1', plays, a, role, in, the, differentiation, of, several, other, cell, types, including, kidney, nephric, mesenchymal, 'cells,', columnar, 'chondrocytes,', and, 'osteoclasts,', indicating, that, 'TRPS-1', involves, in, 'mesenchymal-to-epithelial', cell, transition, '(', 'MET)'])]). relacion([sujeto(['Part', of, the]), verbo([increased]), complemento([secretion, was, related, to, the, 'deleterious,', 'MEFV', p])]). relacion([sujeto(['Patients', with, ulcerative, colitis, '(', 'UC)', who, are, in, clinical, remission, may, still]), verbo([have]), complemento([underlying, endoscopic, 'inflammation,', which, is, associated, with, inferior, clinical, outcomes])]). relacion([sujeto(['The', goal, of, this, study, was, to, determine, the, prevalence, of, active, endoscopic, 'disease,', and, factors]), verbo([associated]), complemento([with, 'it,', in, patients, with, 'UC', who, are, in, clinical, remission])]). relacion([sujeto(['In', a, multivariate, 'model,', variables, independently]), verbo([associated]), complemento([with, a, 'Mayo', endoscopic, score, &, 'gt;1', were, remission, for, &, 'lt;6', months, '(', 'P', =, 0.001, ')', ',', white, blood, count, '(', 'P', =, 0.01, ')', ',', and, 'C-reactive', protein, level, '(', 'P', =, 0.009, ')'])]). relacion([sujeto(['These', parameters, could, be, used, to, identify, patients, who]), verbo([require]), complemento([intensification, of, treatment, to, achieve, mucosal, healing])]). relacion([sujeto(['T-cell', progenitors, seeding, the, thymus]), verbo([retain]), complemento([several, lineage, potentials])]). relacion([sujeto([1, is]), verbo([involved]), complemento([in, the, decision, to, become, a, 'T', cell, or, a, myeloid, 'cell,', and, the, developmental, outcome, of, expressing, 'PU'])]). relacion([sujeto([1, -]), verbo([expressing]), complemento(['T-cell', progenitors, without, 'Notch', signaling, often, adopt, a, myeloid, 'program,', whereas, those, exposed, to, 'Notch', signals, remain, in, a, 'T-lineage', pathway])]). relacion([sujeto(['The', first]), verbo([involves]), complemento([inhibition, of, 'E-proteins', by, 'PU'])]). relacion([sujeto([1, and, the, resulting, inhibition, of, 'Notch', signaling]), verbo([target]), complemento([genes])]). relacion([sujeto([1, to]), verbo([inhibit]), complemento([important, 'T-cell', transcription, factor, genes, such, as, 'Myb,', 'Tcf7', and, 'Gata3', in, the, absence, of, 'Notch', signaling])]). relacion([sujeto(['We', show, that, maintenance, of, 'Gata3', protein, levels, by, 'Myb', and, 'Notch', signaling, is, linked, to, the, ability, to]), verbo([retain]), complemento(['T-cell', identity, in, response, to, 'PU'])]). relacion([sujeto(['Somatic', and, germline, mutations, in, the, dual, 'zinc-finger', transcription, factor, 'GATA3', are]), verbo([associated]), complemento([with, breast, cancers, expressing, the, estrogen, receptor, '(', 'ER)', and, the, autosomal, dominant, 'hypoparathyroidism-deafness-renal', dysplasia, 'syndrome,', respectively])]). relacion([sujeto(['To', elucidate, the, role, of, 'GATA3', in, breast, 'tumorigenesis,', we, investigated, 40, breast, cancers, that]), verbo([expressed]), complemento(['ER,', for, 'GATA3', mutations])]). relacion([sujeto(['Six', different, heterozygous, 'GATA3', somatic, mutations, were, identified, in, eight, 'tumors,', and, these, consisted, 'of:', a, frameshifting, 'deletion/insertion', '(', 944, '_945delGGinsAGC),', an, 'in-frame', deletion, of, a, key, arginine, residue, '(', 991, '_993delAGG),', a, 'seven-nucleotide', frameshifting, insertion, '(', 991, '_992insTGGAGGA),', a, frameshifting, deletion, '(', 1196, '_1197delGA),', and, two, frameshifting, single, nucleotide, insertions, '(', 1224, '_1225insG']), verbo([found]), complemento([in, three, tumors, and, 1224, '_1225insA)'])]). relacion([sujeto(['Five', of, the, eight, mutations, occurred, in, tumors, that]), verbo([retained]), complemento(['GATA3', 'immunostaining,', indicating, that, absence, of, 'GATA3', immunostaining, is, an, unreliable, predictor, of, the, presence, of, 'GATA3', mutations])]). relacion([sujeto(['Luciferase', reporter, 'assays,', electrophoretic, mobility, shift, 'assays,', 'immunofluorescence,', invasion, and, proliferation, assays, demonstrated, that, the, 'GATA3', mutations, resulted, in]), verbo([loss]), complemento(['(', or, 'reduction)', of, 'DNA', 'binding,', decrease, in, transactivational, 'activity,', and, alterations, in, invasiveness, but, not, proliferation])]). relacion([sujeto(['The', 991, '_992insTGGAGGA', '(', 'Arg330', 'frameshift)', mutation]), verbo([led]), complemento([to, a, loss, of, nuclear, 'localization,', yet, the, 991, '_993delAGG', '(', 'Arg330deletion)', retained, nuclear, localization])]). relacion([sujeto(['Investigation', of, the, putative]), verbo([nuclear]), complemento([localization, signal, '(', 'NLS)', sites, showed, that, the, 'NLS', of, 'GATA3', does, not, conform, to, either, a, classical, 'mono-', or, 'bi-partite', 'signal,', but, contains, multiple, cooperative, 'NLS', elements, residing, around, the, 'N-terminal', 'zinc-finger', which, comprises, residues, 264, -, 288])]). relacion([sujeto(['Thus,', approximately, 20, '%', 'ER-positive', breast, cancers]), verbo([have]), complemento([somatic, 'GATA3', mutations, that, lead, to, a, loss, of, 'GATA3', transactivation, activity, and, altered, cell, invasiveness])]). relacion([sujeto(['To', 'date,', there]), verbo([has]), complemento([been, no, study, on, the, relationship, between, microsatellites, in, the, 'GATA3', gene, and, breast, cancer, risk])]). relacion([sujeto(['Also,', the, presence, of, the, 17, -, 'CT', allele]), verbo([has]), complemento([a, positive, relation, with, estrogen, receptor, expression])]). relacion([sujeto(['However,', we]), verbo([found]), complemento([that, the, allelic, length, of, 'GATA3', polymorphisms, had, no, significant, effect, on, the, age, onset, or, grade, of, the, 'disease,', as, well, as, the, expression, of, progesterone, receptors, and, 'HER2'])]). relacion([sujeto(['This', aberration]), verbo([leads]), complemento([to, the, ectopic, activation, of, the, 'PI3K-Akt', 'pathway,', which, promotes, tumor, growth])]). relacion([sujeto(['Here,', we, show, that, the, transcription, factor, 'Gata3', is, progressively, lost, in, 'Pten-deficient', mouse, prostate, tumors, as, a, result, of, both, transcriptional, 'down-regulation', and]), verbo([increased]), complemento([proteasomal, degradation])]). relacion([sujeto(['In', 'Pten-deficient', prostatic, 'ducts,', enforced, 'GATA3']), verbo([prevented]), complemento(['Akt', 'activation,', which, correlated, with, the, 'down-regulation', of, 'Pik3cg', and, 'Pik3c2a', 'mRNAs,', encoding, respectively, class, 'I', and, 'II', 'PI3K', subunits])]). relacion([sujeto(['Remarkably,', the, majority, of, human, prostate, tumors, similarly, show]), verbo([loss]), complemento([of, active, 'GATA3', as, they, progress, to, the, aggressive, 'castrate-resistant', stage])]). relacion([sujeto(['Identification', of, the, transcriptional, networks, that]), verbo([ensure]), complemento([the, proper, specification, and, wiring, of, 'SGNs', during, development, will, lay, the, foundation, for, efforts, to, rewire, a, damaged, cochlea])]). relacion([sujeto(['Here,', we, show, that, the, transcription, factor, 'Gata3,', which, is]), verbo([expressed]), complemento([in, 'SGNs', throughout, their, 'development,', is, essential, for, formation, of, the, intricately, patterned, connections, in, the, cochlea])]). relacion([sujeto(['As', the, first, 'auditory-specific', regulator, of, 'SGN', 'development,', 'Gata3']), verbo([provides]), complemento([a, useful, molecular, entry, point, for, efforts, to, engineer, 'SGNs', for, the, restoration, of, hearing])]). relacion([sujeto(['Infectious', pancreatic, necrosis, virus, '(', 'IPNV)', is, a, highly, contagious, disease]), verbo([causing]), complemento([high, mortalities, in, juvenile, salmonids])]). relacion([sujeto(['Lack', of, correlation, between, neutralizing, antibodies, and, infecting, virus]), verbo([suggests]), complemento([a, likelihood, of, involvement, of, the, cellular, mediated, immune, response, in, vaccine, protection])]). relacion([sujeto(['Analysis', of, 'T-cell', gene, expression, in, lymphoid, organs, '(', headkidney, and, 'spleen)', showed, that, 'GATA-3', was, positively, correlated, with]), verbo([increase]), complemento([in, antibody, levels, when, 'T-bet', was, low])]). relacion([sujeto(['Conversely,', 'T-bet', and, 'FoxP3', were, positively, correlated, with, viral, infection, and, negatively, correlated, with]), verbo([increase]), complemento([in, antibody, levels])]). relacion([sujeto(['Among', the, 'CD8+', 'T', cell, 'genes,', expression, of, eomes, and, 'CD8α', were, positively, correlated, with]), verbo([increase]), complemento([in, viral, copy, numbers, and, negatively, correlated, with, increase, in, antibody, levels])]). relacion([sujeto(['Up-regulation', of, granzyme, 'A', was, highly, correlated, with]), verbo([increase]), complemento([in, viral, copy, numbers, in, the, 'LoAg', and, control, groups, indicating, that, this, gene, could, save, as, a, diagnostic, marker, of, acute, infection, for, 'IPNV', during, acute, infection])]). relacion([sujeto(['These', findings]), verbo([suggest]), complemento([that, functional, signatures, of, the, cellular, mediated, immune, response, could, be, evolutionary, conserved, across, the, vertebrate, taxa, and, that, they, can, effectively, be, used, to, monitor, vaccine, protection, and, infection, progression, of, 'IPNV', in, 'Atlantic', salmon])]). relacion([sujeto(['Evidence']), verbo([suggests]), complemento([that, prenatal, exposure, to, air, pollution, affects, the, ontogeny, and, development, of, the, fetal, immune, system])]). relacion([sujeto(['The', offspring, of, the, 'medium,', high, and, overdose, 'PM-exposed', dams, showed, significantly]), verbo([suppressed]), complemento([splenocyte, proliferation])]). relacion([sujeto(['Decreased', 'interferon-γ', and]), verbo([increased]), complemento(['interleukin-4', levels, in, the, blood, and, 'splenocytes,', and, lowered, 'T-bet', and, elevated, 'GATA-3', mRNA, expressions, were, found, in, the, spleen, in, the, 'medium,', high, and, overdose, groups, when, compared, with, the, control, or, low, dose, group, '(', 'P<0'])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, exposure, of, pregnant, mice, to, 'PM', modulates, the, fetal, immune, 'system,', resulting, in, postnatal, immune, dysfunction, by, exacerbation, of, 'Thl/Th2', deviation])]). relacion([sujeto(['This', deviation, is]), verbo([associated]), complemento([with, altered, 'T-bet', and, 'GATA-3', gene, expressions])]). relacion([sujeto(['The', transcriptional, repressor, 'Bcl6', is, a, critical, regulator, of, 'T', helper, cell, 'fate,', and]), verbo([inhibits]), complemento(['Th2-type', inflammation])]). relacion([sujeto(['We']), verbo([have]), complemento([found, that, 'microRNA-21', '(', 'miR-21)', is, a, novel, target, gene, for, 'Bcl6', in, 'Treg', cells])]). relacion([sujeto(['Bcl6', represses, and, 'Stat3']), verbo([activates]), complemento(['miR-21', transcription, through, a, 'Stat3', binding, element, in, the, 'promoter,', indicating, opposing, regulation, of, 'miR-21', by, the, two, transcription, factors, via, the, same, 'DNA', site])]). relacion([sujeto(['Ectopic', expression, of, 'miR-21']), verbo([promoted]), complemento(['Th2', differentiation, in, 'non-polarized', 'T', cells])]). relacion([sujeto(['The', 'pro-Th2', activity, of, 'miR-21', was]), verbo([associated]), complemento([with, increased, 'Gata3', expression, and, decreased, expression, of, the, 'miR-21', target, gene, 'Sprouty1'])]). relacion([sujeto(['Increased', 'miR-21']), verbo([promoted]), complemento(['Th2', and, 'Treg', gene, expression, in, 'wild-type', 'Tregs'])]). relacion([sujeto(['MiR-21', could, thus, help]), verbo([promote]), complemento([the, 'Th2', bias, of, 'Bcl6-deficient', conventional, 'T', cells, and, 'Treg', cells])]). relacion([sujeto(['MiR21', expression, is]), verbo([increased]), complemento([in, 'Th2-type', 'inflammation,', and, our, results, define, 'miR-21', as, a, critical, target, of, 'Bcl6,', thus, providing, a, new, link, between, 'Bcl6', and, 'Th2', inflammation])]). relacion([sujeto(['Finally,', our, results]), verbo([reveal]), complemento([a, novel, 'T', cell, autonomous, role, for, 'miR-21', in, promoting, 'Th2', differentiation])]). relacion([sujeto(['The', aim, of, this, study, was, to, explore, the, role, of, immune, modulation, therapy, in]), verbo([regulating]), complemento([the, imbalance, of, 'Th1/Th2,', serum, 'IFN-γ,', 'IL-4', and, the, 'T-cell-specific', transcription, factors, 'T-bet/GATA-3', in, peripheral, blood, in, aging, male, patients, with, chronic, cardiac, insufficiency, '(', 'CCI)'])]). relacion([sujeto(['In', 'total,', 156, participants, were, divided, into, three, 'groups:', the, 'CCI', intervention, 'group,', which, received]), verbo([regular]), complemento([therapy, and, thymopetidum, '(', 20, mg, intramuscular, 'injection,', once, every, other, day, for, 3, 'months;', n, =, 70, ')', ',', the, 'CCI', control, 'group,', which, received, regular, therapy, '(', n, =, 56, ')', and, 50, healthy, individuals, older, than, 57, years, of, 'age,', who, served, as, normal, controls])]). relacion([sujeto(['Before', 'therapy,', in, comparison, with, the, control, 'group,', levels, of, left, ventricular, end, diastolic, 'diameter,', 'NT-proBNP,', 'C-reactive', protein, '(', 'CRP),', 'Th1,', 'Th1/Th2,', 'IFN-γ,', and, 'T-bet', mRNA, and, 'T-bet/GATA-3', mRNA, all, 'increased,', and, the, level, of, left, ventricular, ejection, fraction, '(', 'LVEF),', 6, 'MWT,', 'Th2,', 'IL-4,', and, 'GATA-3', mRNA, also]), verbo([decreased]), complemento([in, both, the, 'CCI', intervention, and, control, groups])]). relacion([sujeto(['After', 3, months, of, 'therapy,', levels, of, left, ventricular, end, diastolic, 'diameter,', 'NT-proBNP,', 'CRP,', 'Th1,', 'Th1/Th2,', 'IFN-γ,', 'T-bet', mRNA, and, 'T-bet/GATA-3', mRNA]), verbo([decreased]), complemento([in, the, two, 'CCI', 'subgroups,', but, levels, in, the, 'CCI', intervention, group, were, lower, in, comparison, to, the, control, group])]). relacion([sujeto(['Levels', of, 'LVEF,', 6, 'MWT,', 'Th2', and, 'GATA-3', mRNA]), verbo([increased]), complemento([in, the, two, 'CCI', 'subgroups,', while, levels, in, the, 'CCI', intervention, group, were, higher, in, comparison, with, the, control, group])]). relacion([sujeto(['Immune', modulation, improved, cardiac, function, of, 'CCI', patients, and, was]), verbo([associated]), complemento([with, amelioration, of, 'T-helper', superficial, transcription, factor, polarization, and, its, related, cytokine, imbalance])]). relacion([sujeto(['In', 80, schoolchildren, residing, in, a, 'malaria-endemic', area, of, 'Flores', 'Island,', 'Indonesia,', 'T-helper', 'subsets,', regulatory, 'T-cell', '(', 'Treg)', 'frequencies,', tumor, necrosis, factor, receptor, type, 'II', '(', 'TNFRII)', expression, on, 'Tregs,', and, cytokine, responses]), verbo([induced]), complemento([by, 'Plasmodium', 'falciparum-infected', red, blood, cells, '(', 'RBCs)', were, 'measured,', and, values, for, asymptomatic, infected, subjects, were, compared, to, those, for, uninfected, controls])]). relacion([sujeto(['To', ascertain, that, alterations]), verbo([found]), complemento([were, due, to, the, presence, of, malaria, 'parasites,', the, immune, responses, were, analyzed, in, 16, children, before, and, 1, month, after, antimalarial, treatment])]). relacion([sujeto(['TNFRII', 'expression,', a, marker, of, activation, on, 'Tregs,', was, higher, during, infection, but]), verbo([decreased]), complemento([upon, treatment])]). relacion([sujeto(['falciparum-infected', 'RBCs', appeared, to, be]), verbo([suppressed]), complemento([by, plasmodial, 'infection,', as, both, increased, after, antimalarial, treatment])]). relacion([sujeto(['Malaria', parasites]), verbo([associated]), complemento([with, asymptomatic, infections, seem, to, result, in, increased, 'TNFRII', expression, on, 'Tregs,', as, well, as, suppressed, 'Th2', cytokine, 'responses,', features, that, might, be, important, for, survival, of, the, parasites, in, asymptomatic, carriers])]). relacion([sujeto(['Although', other, studies]), verbo([have]), complemento([shown, how, 'T', cell, receptor, '(', 'TcR)', signals, induce, the, 'up-regulation', of, 'GATA3', expression, in, 'Treg', 'cells,', the, underlying, mechanism, that, maintains, 'GATA3', expression, in, 'Treg', cells, remains, unclear])]). relacion([sujeto(['Here,', we, show, how, 'USP21']), verbo([interacts]), complemento([with, and, stabilizes, 'GATA3', by, mediating, its, deubiquitination])]). relacion([sujeto(['In', a, 'T', cell, line, 'model,', we]), verbo([found]), complemento([that, 'TcR', stimulation, promoted, 'USP21', 'expression,', which, was, further, 'up-regulated', in, the, presence, of, 'FOXP3'])]). relacion([sujeto(['The', 'USP21', mutant, 'C221A', reduced, its, capacity, to, stabilize, 'GATA3', 'expression,', and, its, knockdown]), verbo([led]), complemento([to, the, 'down-regulation', of, 'GATA3', protein, expression, in, 'Treg', cells])]). relacion([sujeto(['Furthermore,', we]), verbo([found]), complemento([that, 'FOXP3', could, directly, bind, to, the, 'USP21', gene, promoter, and, activated, its, transcription, upon, 'TcR', stimulation])]). relacion([sujeto(['Finally,', 'USP21,', 'GATA3,', and, 'FOXP3', were]), verbo([found]), complemento(['up-regulated', in, 'Treg', cells, that, were, isolated, from, asthmatic, subjects])]). relacion([sujeto(['In', 'summary,', we]), verbo([have]), complemento([identified, a, 'USP21-mediated', pathway, that, promotes, 'GATA3', stabilization, and, expression, at, the, 'post-translational', level])]). relacion([sujeto(['Tumour', cells, are, influenced, by, their, 'microenvironment,', which, can]), verbo([promote]), complemento([uncontrolled, 'growth,', invasion, and, metastasis])]). relacion([sujeto(['The', 'GATA3', transcription, factor, is, now, shown, to]), verbo([regulate]), complemento([the, tumour, microenvironment, by, inducing, the, expression, of, 'miR-29b', in, cancer, cells])]). relacion([sujeto(['This', microRNA, in, turn]), verbo([inhibits]), complemento([the, expression, of, genes, involved, in, angiogenesis, and, extracellular, matrix, signalling, and, remodelling, to, suppress, metastasis])]). relacion([sujeto(['In', 'addition,', we]), verbo([report]), complemento(['GATA3', expression, in, matched, primary, and, metastatic, breast, carcinomas, in, 30, patients, with, known, estrogen, receptor, '(', 'ER),', progesterone, receptor, '(', 'PR),', and, 'Her-2', 'status,', including, 5, with, 'ER', 'and/or', 'PR', loss, from, primary, to, metastasis])]). relacion([sujeto(['GATA3', labeling, was, overwhelmingly]), verbo([maintained]), complemento([in, paired, metastases])]). relacion([sujeto(['Notably,', 'GATA3', was]), verbo([maintained]), complemento([in, all, &, 'quot;luminal', 'loss"', 'metastases,', which, showed, 'ER', 'and/or', 'PR', loss])]). relacion([sujeto(['In', 'conclusion,', 'GATA3', expression, is]), verbo([maintained]), complemento([between, matched, primary, and, metastatic, carcinomas, including, 'ER-negative', cases])]). relacion([sujeto(['Fusions', of, the, tyrosine, kinase, domain, of, 'JAK2', with, multiple, partners, occur, in, 'leukemia/lymphoma', where, they, reportedly]), verbo([promote]), complemento(['JAK2-oligomerization', and, autonomous, 'signalling,', 'Affected', entities, are, promising, candidates, for, therapy, with, 'JAK2', signalling, inhibitors])]). relacion([sujeto(['While', 'JAK2-translocations', occur, in, 'myeloid,', 'B-cell', and, 'T-cell', lymphoid, 'neoplasms,', our, findings]), verbo([suggest]), complemento([their, incidence, among, the, last, group, is, low])]). relacion([sujeto(['To', investigate, 'signalling,', 'PCM1-JAK2', was, subjected, to, lentiviral, knockdown, which]), verbo([inhibited]), complemento([7, top, upregulated, genes, in, 't(8;9)', 'cells,', notably, 'SOCS2/3'])]). relacion([sujeto(['SOCS3,', but, not, 'SOCS2,', was, also, upregulated, in, a, chronic, eosinophilic, leukemia, bearing, 'PCM1-JAK2,', highlighting, its, role, as, a, central, signalling]), verbo([target]), complemento([of, 'JAK2', translocation, neoplasia])]). relacion([sujeto(['PCM1-JAK2', signalling]), verbo([required]), complemento(['pSTAT5,', supporting, a, general, paradigm, of, 'STAT5', activation, by, 'JAK2', alterations, in, lymphoid, malignancies])]). relacion([sujeto(['Our', data, support, further, investigation, of, 'SOCS2/3', as, signalling, 'effectors,', prognostic, indicators, and, potential, therapeutic]), verbo([targets]), complemento([in, cancers, with, 'JAK2', rearrangements])]). relacion([sujeto(['Early', 'T-cell', precursor, acute, lymphoblastic, leukemia, '(', 'ETP-ALL)']), verbo([has]), complemento([been, identified, as, 'high-risk', subgroup, of, acute, 'T-lymphoblastic', leukemia, '(', 'T-ALL)', with, a, high, rate, of, 'FLT3-mutations', in, adults])]). relacion([sujeto(['Interestingly,', we]), verbo([found]), complemento([a, high, rate, of, 'FLT3-mutations', in, 'ETP-ALL', samples, '(', n, =, 24, ',', 35, '%', ')'])]). relacion([sujeto(['To', further, explore, the, efficacy, of]), verbo([targeted]), complemento(['therapies,', we, demonstrate, that, 'T-ALL', cell, lines, transfected, with, 'FLT3', expression, constructs, were, particularly, sensitive, to, tyrosine, kinase, inhibitors])]). relacion([sujeto(['Despite', advances, in, our, understanding, of, breast, 'cancer,', patients, with, metastatic, disease]), verbo([have]), complemento([poor, prognoses])]). relacion([sujeto(['GATA3', is, a, transcription, factor, that, specifies, and]), verbo([maintains]), complemento([mammary, luminal, epithelial, cell, 'fate,', and, its, expression, is, lost, in, breast, 'cancer,', correlating, with, a, worse, prognosis, in, human, patients])]). relacion([sujeto(['Here,', we, show, that, 'GATA3']), verbo([promotes]), complemento(['differentiation,', suppresses, metastasis, and, alters, the, tumour, microenvironment, in, breast, cancer, by, inducing, 'microRNA-29b', '(', 'miR-29b)', expression])]). relacion([sujeto(['Accordingly,', 'miR-29b', is, enriched, in, luminal, breast, cancers, and]), verbo([loss]), complemento([of, 'miR-29b,', even, in, 'GATA3-expressing', 'cells,', increases, metastasis, and, promotes, a, mesenchymal, phenotype])]). relacion([sujeto(['Mechanistically,', 'miR-29b']), verbo([inhibits]), complemento([metastasis, by, targeting, a, network, of, 'pro-metastatic', regulators, involved, in, 'angiogenesis,', collagen, remodelling, and, 'proteolysis,', including, 'VEGFA,', 'ANGPTL4,', 'PDGF,', 'LOX', and, 'MMP9,', and, targeting, 'ITGA6,', 'ITGB1', and, 'TGFB,', thereby, indirectly, affecting, differentiation, and, epithelial, plasticity])]). relacion([sujeto(['The', discovery, that, a, 'GATA3-miR-29b', axis]), verbo([regulates]), complemento([the, tumour, microenvironment, and, inhibits, metastasis, opens, up, possibilities, for, therapeutic, intervention, in, breast, cancer])]). relacion([sujeto(['Henoch-Schönlein', purpura, '(', 'HSP),', the, most, common, type, of, leukocytoclastic, 'vasculitis,', is]), verbo([caused]), complemento([by, 'T', 'cell-mediated', autoimmune, reactions])]). relacion([sujeto(['Our', results, show, that, histone, 'H3', acetylation, and, methylation, are, significantly]), verbo([enhanced]), complemento([in, 'PBMCs', from, 'HSP', patients])]). relacion([sujeto(['We', also, demonstrate, specifically, that, marked]), verbo([increases]), complemento([in, histone, 'H3', acetylation, and, 'H3', lysine, 4, trimethylation, occur, at, the, 'IL-4', loci, in, these, patients])]). relacion([sujeto(['These', findings]), verbo([suggest]), complemento([that, abnormal, histone, modifications, are, present, in, the, 'PBMCs', of, patients, with, 'HSP,', possibly, contributing, to, the, activation, of, pathological, immune, responses, associated, with, 'HSP'])]). relacion([sujeto(['Genotoxic', stress, and, 'RAS']), verbo([induce]), complemento([the, expression, of, 'CD155,', a, ligand, for, the, immune, receptors, 'DNAM-1,', 'CD96', and, 'TIGIT'])]). relacion([sujeto(['In', 'addition,', 'IRF3,', but, not, 'IRF7,']), verbo([modulated]), complemento(['CD155', upregulation, in, response, to, 'TLR3', signals])]). relacion([sujeto(['Immunization', of, 'CD155-deficient', mice, with, 'OVA', and, the, 'TLR9', agonist, 'CpG', resulted, in]), verbo([increased]), complemento(['OVA-specific', 'IgG2a/c', titers, when, compared, to, wild, type, mice])]). relacion([sujeto(['Splenocytes', of, immunized, 'CD155-deficient', mice, secreted, lower, levels, of, 'IL-4', and, fewer, 'IL-4', and, 'GATA-3']), verbo([expressing]), complemento(['CD4(+)', 'T', cells, were, present, in, the, spleen, of, 'Cd155(-/-)', mice])]). relacion([sujeto(['Our', data]), verbo([suggest]), complemento([that, 'CD155', regulates, 'T(h)2', differentiation])]). relacion([sujeto(['Glandular', neoplasms]), verbo([involving]), complemento([the, urinary, bladder, carry, a, challenging, differential, diagnosis, including, primary, and, secondary, processes])]). relacion([sujeto(['Urothelial', carcinoma, with, glandular, differentiation, '(', 11, ')', ',', colorectal, adenocarcinoma, secondarily]), verbo([involving]), complemento([the, bladder, '(', 25, ')', ',', and, primary, colorectal, adenocarcinoma, '(', 22, ')', were, also, analyzed, and, the, results, were, compared, using, a, 'Fisher', exact, test])]). relacion([sujeto(['Cadherin-17', was]), verbo([expressed]), complemento([in, 23, /, 25, primary, bladder, adenocarcinomas, '(', 92, '%', ')', ',', 23, /, 25, colorectal, adenocarcinomas, involving, the, bladder, '(', 92, '%', ')', ',', 21, /, 22, primary, colorectal, adenocarcinomas, '(', 95, '%', ')', and, entirely, negative, '(', 0, /, 11, ')', in, both, components, of, urothelial, carcinoma, with, glandular, differentiation, '(', 'P<0'])]). relacion([sujeto(['In', urothelial, carcinoma, with, glandular, 'differentiation,', positive]), verbo([nuclear]), complemento([staining, for, 'GATA3', was, evident, in, the, urothelial, component, for, 18, '%', '(', 2, /, 11, ')', and, the, glandular, component, for, 9, '%', '(', 1, /, 11, ')', with, additional, tumors, showing, only, cytoplasmic, staining])]). relacion([sujeto(['Positive']), verbo([nuclear]), complemento([and, cytoplasmic, immunostaining, for, 'β-catenin', was, evident, in, 21, /, 22, primary, colorectal, adenocarcinomas, '(', 95, '%', ')', and, 23, /, 25, cases, of, secondary, involvement, by, colorectal, adenocarcinoma, '(', 92, '%', ')'])]). relacion([sujeto([p63, was]), verbo([expressed]), complemento([only, in, the, urothelial, component, of, urothelial, carcinoma, with, glandular, differentiation, and, not, in, the, glandular, component, '(', 'P<0'])]). relacion([sujeto(['To', observe, the, effect, of, autoblood, 'acupoint-injection', '(', 'ABAI)', on, expression, levels, of, pulmonary, transacting, 'T-cell-specific', transcription, factor, 'GATA', 3, '(']), verbo([involving]), complemento(['Th', 2, cytokine, 'expression),', 'Th', 1, -, specific, 'T-box', transcription, factor, 'T-box', expressed, in, 'T-cells', '(', 'T-bet)', proteins, and, genes, in, asthmatic, rats, so, as, to, explore, its, mechanisms, underlying, asthma, relief])]). relacion([sujeto(['No', significant, differences, were]), verbo([found]), complemento([between, model, and, 'SAI', 'groups,', and, between, 'ABAI', and, 'DXM', groups, in, 'GATA', 3, protein, expression, 'levels;', and, between, 'ABAI', and, 'DXM', groups, in, 'GATA', 3, mRNA, expression, 'levels;', between, normal, and, model, 'groups,', and, between, 'SAI', and, 'ABAI', groups, in, 'T-bet', protein, expression, 'levels;', between, model, and, 'SAI', groups, and, between, 'ABAI', and, 'DXM', groups, in, 'T-bet', mRNA, expression, levels, '(', 'P', &, 'gt;', 0.05, ')'])]). relacion([sujeto(['Autoblood', acupoint, injection, is, comparable, to, 'DXM', intraperitoneal, injection, in, 'down-regulating', 'asthma-induced']), verbo([increase]), complemento([of, pulmonary, 'GATA', 3, protein, and, mRNA, expression, as, well, as, ratio, of, 'GATA', 3, 'mRNA/T-bet', 'mRNA,', and, in, 'up-regulating', 'asthma-induced', decrease, of, 'T-bet', mRNA, expression, in, asthma, 'rats,', which, may, contribute, to, their, effects, in, relieving, asthma])]). relacion([sujeto(['Epithelial-to-mesenchymal', transition]), verbo([has]), complemento([been, shown, to, correlate, with, therapy, 'resistance,', but, the, functional, link, and, signalling, pathways, remain, to, be, elucidated])]). relacion([sujeto(['Here', we]), verbo([report]), complemento([that, 'microRNA-30c,', a, human, breast, tumour, prognostic, 'marker,', has, a, pivotal, role, in, chemoresistance, by, a, direct, targeting, of, the, 'actin-binding', protein, twinfilin, 1, ',', which, promotes, 'epithelial-to-mesenchymal', transition])]). relacion([sujeto(['An', 'interleukin-6', family, 'member,', 'interleukin-11', is, identified, as, a, secondary]), verbo([target]), complemento([of, twinfilin, 1, in, the, 'microRNA-30c', signalling, pathway])]). relacion([sujeto(['Our', study, demonstrates, that, 'microRNA-30c', is, transcriptionally]), verbo([regulated]), complemento([by, 'GATA3', in, breast, tumours])]). relacion([sujeto(['Identification', of, a, novel, 'microRNA-mediated', pathway, that]), verbo([regulates]), complemento([chemoresistance, in, breast, cancer, will, facilitate, the, development, of, novel, therapeutic, strategies])]). relacion([sujeto(['HANABA', 'TARANU', '(', 'HAN)', encodes, a, 'boundary-expressed', 'GATA3-type', transcription, factor, that]), verbo([regulates]), complemento([shoot, meristem, organization, and, flower, development, in, 'Arabidopsis', 'thaliana,', but, the, underlying, mechanism, remains, unclear])]). relacion([sujeto(['Through', 'time-course', microarray, analyses, following, transient, overexpression, of, 'HAN,', we]), verbo([found]), complemento([that, 'HAN', represses, hundreds, of, 'genes,', especially, genes, involved, in, hormone, responses, and, floral, organ, specification])]). relacion([sujeto(['Genetic', analysis, indicates, that, 'HAN', and, the, three, 'GATA3', family, genes, coordinately]), verbo([regulate]), complemento([floral, 'development,', and, their, expression, patterns, are, partially, overlapping])]). relacion([sujeto(['HAN', can, homodimerize, and]), verbo([heterodimerize]), complemento([with, the, three, proteins, encoded, by, these, 'genes,', and, 'HAN', directly, binds, to, its, own, promoter, and, the, 'GNC', promoter, in, vivo])]). relacion([sujeto(['These', 'findings,', along, with, the, fact, that, constitutive, overexpression, of, 'HAN', produces, an, even, stronger, phenotype, than, the, 'loss-of-function', 'mutation,', support, the, hypothesis, that, 'HAN', functions, as, a, key, repressor, that]), verbo([regulates]), complemento([floral, development, via, regulatory, networks, involving, genes, in, the, 'GATA3', 'family,', along, with, genes, involved, in, hormone, action, and, floral, organ, specification])]). relacion([sujeto(['Murine', model, of, 'ALI', was, subsequently]), verbo([induced]), complemento([by, an, 'intra-tracheal', instillation, of, lipopolysaccharide, '(', 'LPS)', and, lung, specimens, were, harvested, 24, hours, later])]). relacion([sujeto(['FLT3L', pretreatment, further]), verbo([stimulated]), complemento([the, accumulation, and, maturation, of, pulmonary, 'cDCs,', leading, to, a, marked, deterioration, of, 'LWW/BW', and, lung, histopathological, changes])]). relacion([sujeto(['In', 'contrast,', the, lestaurtinib, pretreatment]), verbo([inhibited]), complemento([the, accumulation, and, maturation, of, pulmonary, 'cDCs,', leading, to, a, significant, improvement, of, 'LWW/BW', and, lung, histopathological, changes])]). relacion([sujeto(['The', administration, of, lestaurtinib, also]), verbo([suppressed]), complemento([the, lung, 'MPO', activity, and, 'T-bet/GATA-3', mRNA, ratio, in, the, lung])]). relacion([sujeto(['FLT3', signaling, attenuates, 'ALI', by]), verbo([regulating]), complemento([the, accumulation, and, maturation, of, pulmonary, 'cDCs,', indicating, a, potential, pharmacotherapy, for, 'ALI'])]). relacion([sujeto(['Evaluation', of, 'CD8(+)', 'T', cell, status, in, 'blood,', 'spleen,', 'TDLN,', 'VDLN', and, tumor, revealed]), verbo([increase]), complemento([in, cellular, number])]). relacion([sujeto(['NLGP', treatment]), verbo([enhances]), complemento([type, 1, polarized, 'T-bet', expressing, 'T', cells, with, downregulation, of, 'GATA3'])]). relacion([sujeto(['However,', 'T∶Treg', ratios, significantly]), verbo([increased]), complemento([with, 'NLGP'])]). relacion([sujeto(['Reinoculation', of, sarcoma, cells, in, tumor, regressed, 'NLGP-treated', mice]), verbo([maintained]), complemento([tumor, free, status, in, majority])]). relacion([sujeto(['Submicroscopic', duplications, in, the, 'Miller-Dieker', critical, region]), verbo([have]), complemento([been, recently, described, as, new, genomic, disorders])]). relacion([sujeto(['To', 'date,', only, a, few, cases]), verbo([have]), complemento([been, reported, with, overlapping, 17, p13])]). relacion([sujeto(['In', this, 'study,', we, 'describe,', to, our, knowledge, for, the, first, 'time,', a, 5, -, 'year-old', female, patient, with, intellectual, disability, who]), verbo([has]), complemento([an, unbalanced, 10, ;, 17, translocation, inherited, from, the, father])]). relacion([sujeto(['The', girl, was, diagnosed, by, subtelomeric, 'FISH', and, 'array-CGH,', showing, a, 4.43, -, 'Mb', heterozygous, deletion, on, chromosome, 10, p, that]), verbo([involved]), complemento([14, genes, and, a, 3.22, -, 'Mb', 'single-copy', gain, on, chromosome, 17, 'p,', which, includes, the, critical, region, of, the, 'Miller-Dieker', syndrome, and, 61, genes])]). relacion([sujeto(['Because', our, patient, exhibits, a, combination, of, 2, 'imbalances,', she]), verbo([has]), complemento([phenotypic, features, of, both, chromosome, 'abnormalities,', which, have, been, reported, separately])]). relacion([sujeto(['Interestingly,', the, majority, of, patients, who, carry, the, deletion, 10, p]), verbo([have]), complemento([visual, and, auditory, deficiencies, that, are, attributed, to, loss, of, the, 'GATA3', gene])]). relacion([sujeto(['However,', our, patient, also, presents, severe, hearing, and, visual, problems, even, though, 'GATA3', is, 'present,']), verbo([suggesting]), complemento([the, involvement, of, different, genes, that, affect, the, development, of, the, visual, and, auditory, systems])]). relacion([sujeto(['Understanding', the, cellular, mechanisms, and, pathways]), verbo([involved]), complemento([in, extraembryonic, '(', 'ExE)', differentiation, is, of, great, interest, because, of, the, important, role, of, this, process, in, maternal, health, and, fertility])]). relacion([sujeto(['Fibroblast', growth, factor, 2, '(', 'FGF-2)', is, widely, used, to]), verbo([maintain]), complemento([the, 'self-renewal', of, hESCs, and, induced, pluripotent, stem, 'cells,', while, all, trans, retinoic, acid, '(', 'RA)', is, used, to, facilitate, the, directed, differentiation, of, hESCs])]). relacion([sujeto(['Here,', we, monitored, the, 'RA']), verbo([induced]), complemento([differentiation, of, hESCs, to, the, 'ExE', lineage, with, and, without, 'FGF-2', over, a, 7, -, day, period, via, global, transcriptional, profiling])]). relacion([sujeto(['Many', of, the, differentially]), verbo([expressed]), complemento([genes, were, involved, in, 'WNT', and, 'TGF-β', signaling])]). relacion([sujeto(['RA', inactivated, 'WNT', signaling, even, in, the, presence, of, exogenous, 'FGF-2,', which, that]), verbo([promotes]), complemento([the, maintenance, of, the, pluripotent, state])]). relacion([sujeto(['We', also, show, that, 'BMP4', was, upregulated, and, that, 'RA', was, able, to]), verbo([modulate]), complemento([the, 'TGF-β', signaling, pathway, and, direct, hESCs, toward, the, 'ExE', lineage])]). relacion([sujeto(['In', 'addition,', an, epigenetic, study, revealed, hypermethylation, of, the, 'DDAH2,', 'TDGF1', and, 'GATA3', gene, 'promoters,']), verbo([suggesting]), complemento([a, role, for, epigenetic, regulation, during, 'ExE', differentiation])]). relacion([sujeto(['These', data]), verbo([reveals]), complemento([that, the, effect, of, 'RA', prevails, in, the, presence, of, exogenous, 'FGF-2', thus, resulting, in, the, direction, of, hESCs, toward, the, 'ExE', lineage])]). relacion([sujeto(['This', study, aimed, to, determine, if, pneumococcal, polysaccharide, vaccine, '(', 'PPV)', could]), verbo([suppress]), complemento([allergic, inflammation, in, an, allergic, rhinitis, mouse, model, and, to, explore, whether, differences, exist, regarding, the, effect, of, 'PPV', according, to, timing, of, administration])]). relacion([sujeto(['In', the, 'Pre-S', 'group,', symptom, 'score,', serum, 'Der', 'f-specific', 'IgE,', 'eosinophils,', 'IL-13,', and, 'GATA-3', mRNA, were]), verbo([decreased]), complemento(['(', 'P', &, 'lt;'])]). relacion([sujeto([5, ')', ',', and, 'IL-10,', 'Foxp3', 'mRNA,', and, 'CD4(+)CD25(+)Foxp3(+)', 'T', cells, were]), verbo([increased]), complemento([compared, with, those, in, 'Der', f, group, '(', 'P', &, 'lt;'])]). relacion([sujeto(['In', the, 'Post-S', 'group,', symptom, 'score,', serum, 'Der', 'f-specific', 'IgE,', and, 'GATA-3', mRNA, were]), verbo([decreased]), complemento(['(', 'P', &, 'lt;'])]). relacion([sujeto([5, ')', ',', and, 'Foxp3', mRNA, and, 'CD4(+)CD25(+)Foxp3(+)', 'T', cells, were]), verbo([increased]), complemento([compared, with, those, in, the, 'Der', f, group, '(', 'P', &, 'lt;'])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, 'PPV', administered, before, or, after, sensitization, suppresses, 'Th2', response, and, enhanced, induction, of, regulatory, 'T', cells, in, an, allergic, rhinitis, model])]). relacion([sujeto(['The', transcription, factor, 'Runx3']), verbo([inhibits]), complemento(['CD4(+)', 'T-cell', differentiation, by, repressing, 'Cd4', gene, 'expression;', 'accordingly,', 'Runx3', is, not, expressed, in, 'DP', thymocytes, or, developing, 'CD4(+)', 'T', cells])]). relacion([sujeto(['The', transcription, factor, 'Thpok', is, upregulated, in, 'CD4-differentiating', thymocytes, and]), verbo([required]), complemento([to, repress, 'Runx3'])]). relacion([sujeto(['Here', we, show, that, 'Gata3,', a, transcription, factor, preferentially, and, transiently, upregulated, by, 'CD4(+)', 'T-cell', 'precursors,', represses, 'Runx3', and]), verbo([binds]), complemento([the, 'Runx3', locus, in, vivo])]). relacion([sujeto(['Furthermore,', whereas, 'Runx3', represses, 'Cd4,', we, show, that, 'Gata3']), verbo([promotes]), complemento(['Cd4', expression, in, 'Thpok-deficient', thymocytes])]). relacion([sujeto(['Thus,', in, addition, to, its, previously, documented, role, in]), verbo([promoting]), complemento(['CD4-lineage', 'gene-expression,', 'Gata3', represses, 'CD8-lineage', gene, expression])]). relacion([sujeto(['T-bet', and, 'GATA-3', are, known, to]), verbo([regulate]), complemento([cytokine, expression, in, 'T', 'lymphocytes,', and, cytokines, have, been, implicated, in, endometrial, regulation, and, implantation])]). relacion([sujeto(['Previous', work, showed, that, female, steroid, hormones]), verbo([modulate]), complemento([the, expression, of, 'T-bet', in, endometrial, epithelial, 'cells,', suggesting, a, mechanism, for, local, immune, regulation, in, the, human, endometrium])]). relacion([sujeto(['We', hypothesized, that, stromal, cells, are]), verbo([involved]), complemento([in, immune, 'regulation,', as, they, have, been, shown, to, exert, paracrine, effects, on, other, endometrial, cells, and, compartments, and, also, secrete, cytokines])]). relacion([sujeto(['T-bet', and, 'IL-4', mRNA, expression]), verbo([increased]), complemento([and, 'GATA-3', decreased, under, decidualization, 'conditions;', 'IFN-γ', was, not, detected])]). relacion([sujeto(['Secretion', of, 'IL-15']), verbo([increased]), complemento([during, 'decidualization,', and, 'IL-15', upregulated, 'T-bet', gene, expression])]). relacion([sujeto(['Although', first, identified, in, association, with, a, chromosomal, translocation, in, 'T-ALL,', the, ectopic, expression, of, 'LMO1', occurs, far, more, frequently, in, the, absence, of, any, known, mutation]), verbo([involving]), complemento([its, locus])]). relacion([sujeto(['Given', that, 'LMO1', is, barely]), verbo([expressed]), complemento([in, any, haematopoietic, 'lineage,', and, activation, of, transcriptional, drivers, in, leukaemic, cells, is, not, well, 'described,', we, investigated, the, regulation, of, this, gene, in, normal, haematopoietic, and, leukaemic, cells])]). relacion([sujeto(['We', show, that, 'LMO1']), verbo([has]), complemento([two, promoters, that, drive, reporter, gene, expression, in, transgenic, mice, to, neural, tissues, known, to, express, endogenous, 'LMO1'])]). relacion([sujeto(['The', 'LMO1', promoters, become]), verbo([activated]), complemento([in, 'T-ALL', together, with, the, 3, '\'', 'enhancer,', which, is, bound, in, primary, 'T-ALL', cells, by, 'SCL/TAL1', and, 'GATA3'])]). relacion([sujeto(['Taken', 'together,', our, results, show, that, 'LMO1', is, poised, for, expression, in, normal, 'progenitors,', where, activation, of, 'SCL/TAL1', together, with, a, breakdown, of, epigenetic, repression, of, 'LMO1', regulatory, elements]), verbo([induces]), complemento([ectopic, 'LMO1', expression, that, contributes, to, the, development, and, maintenance, of, 'T-ALL'])]). relacion([sujeto(['Thymic', stromal, lymphopoietin, '(', 'TSLP),', an, 'epithelium-derived', 'cytokine,', can, strongly]), verbo([activate]), complemento([lung, dendritic, cells, '(', 'DCs)', through, the, 'TSLP-TSLPR', and, 'OX40L-OX40', signaling, pathways, to, promote, 'Th2', differentiation])]). relacion([sujeto(['To', determine, whether, 'TSLP', is, the, underlying]), verbo([trigger]), complemento([of, airway, remodeling, in, chronic, 'allergen-induced', 'asthma,', we, induced, allergic, airway, inflammation, in, mice, by, intranasal, administration, of, house, dust, mite, '(', 'HDM)', extracts, for, up, to, 5, consecutive, weeks])]). relacion([sujeto(['We', showed, that, repeated, respiratory, exposure, to, 'HDM']), verbo([caused]), complemento([significant, airway, eosinophilic, 'inflammation,', peribronchial, collagen, 'deposition,', goblet, cell, 'hyperplasia,', and, airway, hyperreactivity, '(', 'AHR)', to, methacholine])]). relacion([sujeto(['Moreover,', the, levels, of, 'TSLP', and, transforming, growth, factor, beta, 1, '(', 'TGF-β1)', were, also]), verbo([increased]), complemento([in, the, airway])]). relacion([sujeto(['We', further, 'demonstrated,', using, the, chronic, 'HDM-induced', asthma, 'model,', that, the, inhibition, of, 'Th2', responses, via, neutralization, of, 'TSLP', with, an, 'anti-TSLP', mAb, reversed, airway, 'inflammation,']), verbo([prevented]), complemento([structural, 'alterations,', and, decreased, 'AHR', to, methacholine, and, 'TGF-β1', level])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, 'TSLP', plays, a, pivotal, role, in, the, initiation, and, persistence, of, airway, inflammation, and, remodeling, in, the, context, of, chronic, allergic, asthma])]). relacion([sujeto(['EMT']), verbo([has]), complemento([emerged, as, a, unifying, 'concept,', involving, 'cell-cell', 'adhesion,', migration, and, apoptotic, pathways])]). relacion([sujeto(['Recently,', a, link, between, 'Slug/Snai2', and, stemness]), verbo([has]), complemento([been, described, in, mammary, epithelial, 'cells,', but, 'EMT', master, genes, actual, 'localization,', role, and, targets, during, mammary, gland, morphogenesis, are, not, known, and, we, focused, on, this, basic, question])]). relacion([sujeto(['Other', 'EMT', master, genes, were, 'overexpressed,']), verbo([suggesting]), complemento([compensation, mechanisms])]). relacion([sujeto(['In', 'addition,', they, showed, that, 'Slug']), verbo([enhances]), complemento([specifically, clonal, mammosphere, emergence, and, 'growth,', cell, 'motility,', and, represses, apoptosis])]). relacion([sujeto(['Overall,', our, data, better, define, a, key, mechanism, coordinating, cell, lineage, dynamics, and, 'morphogenesis,', and]), verbo([provide]), complemento([physiological, relevance, to, broadening, 'EMT', pathways])]). relacion([sujeto(['The', 'E2A', transcription, factors]), verbo([promote]), complemento([the, development, of, 'thymus-seeding', 'cells,', but, it, remains, unknown, whether, these, proteins, play, a, role, in, 'T', lymphocyte, lineage, specification, or, commitment])]). relacion([sujeto(['Here,', we, showed, that, 'E2A', proteins, were]), verbo([required]), complemento([to, promote, 'T-lymphocyte', commitment, from, 'DN2', thymocytes, and, to, extinguish, their, potential, for, alternative, fates])]). relacion([sujeto(['E2A', proteins, functioned, in, 'DN2', cells, to, limit, expression, of, 'Gata3,', which, encodes, an, essential, 'T-lymphocyte', transcription, factor, whose, ectopic, expression, can]), verbo([arrest]), complemento(['T-cell', differentiation])]). relacion([sujeto(['Our', data, support, a, novel, paradigm, in, lymphocyte, lineage, commitment, in, which, the, 'E2A', proteins, are, necessary, to, limit, the, expression, of, an, essential, lineage, specification, and, commitment, factor, to, restrain, 'self-renewal', and, to]), verbo([prevent]), complemento([an, arrest, in, differentiation])]). relacion([sujeto(['Although', 'Ag-specific', airway, inflammation, and, hyperresponsiveness, were]), verbo([induced]), complemento([in, each, 'mouse,', the, phenotype, of, inflammation, showed, a, distinct, difference, that, was, dependent, upon, the, genotype])]). relacion([sujeto(['Interestingly,', airway, hyperresponsiveness, accompanied, by, neutrophilic, airway, inflammation, in, 'RORγt-overexpressing', mice, was, effectively]), verbo([suppressed]), complemento([by, 'anti-IL-17', 'Ab,', 'CXCR2', 'antagonist,', or, 'anti-IL-6R', 'Ab', administration])]). relacion([sujeto(['In', 'conclusion,', our, results]), verbo([suggest]), complemento([that, the, expression, levels, of, 'GATA-3', and, 'RORγt', may, be, important, for, determining, the, phenotype, of, asthmatic, airway, inflammation])]). relacion([sujeto(['One', critical, checkpoint]), verbo([involves]), complemento(['Notch1', signaling, that, instructs, 'T-cell', commitment, at, the, expense, of, the, 'B-lineage', program])]). relacion([sujeto(['While', 'GATA-3', is]), verbo([required]), complemento([for, 'T-cell', 'specification,', its, mechanism, of, action, is, poorly, understood])]). relacion([sujeto(['First,', 'GATA-3', orchestrates, a, transcriptional, '“', 'repertoire”', that, is]), verbo([required]), complemento([for, thymocyte, maturation, up, to, and, beyond, the, 'pro-T-cell', stage])]). relacion([sujeto(['Second,', 'GATA-3', critically]), verbo([suppresses]), complemento([a, latent, 'B-cell', potential, in, 'pro–T', cells])]). relacion([sujeto(['As', 'such,', 'GATA-3', is, essential, to, sealing, in, 'Notch-induced', 'T-cell', fate, in, early, thymocyte, precursors, by]), verbo([promoting]), complemento(['T-cell', identity, through, the, repression, of, alternative, developmental, options])]). relacion([sujeto(['We', analyzed, variant, genotypes, hypothesized, to, modify, major, biological, processes]), verbo([involved]), complemento([in, bladder, 'carcinogenesis,', including, hormone, 'regulation,', 'apoptosis,', 'DNA', 'repair,', immune, 'surveillance,', 'metabolism,', 'proliferation,', and, telomere, maintenance])]). relacion([sujeto(['The', 3, '\'', 'UTR', flanking, variant, form, of, the, hormone, regulation, gene, 'HSD3B2', was]), verbo([associated]), complemento([with, increased, bladder, cancer, risk, in, the, 'New', 'Hampshire', population, '(', adjusted, 'OR', 1.85, 95, '%', 'CI', 1.31, -, 2.62, ')'])]). relacion([sujeto(['This']), verbo([finding]), complemento([was, successfully, replicated, in, the, 'Texas', 'Bladder', 'Cancer', 'Study', with, 957, 'controls,', 497, cases, '(', adjusted, 'OR', 3.66, 95, '%', 'CI', 1.06, -, 12.63, ')'])]). relacion([sujeto(['The', fact, that, bladder, cancer, incidence, is, 3, -, 4, times, higher, in, males]), verbo([suggests]), complemento([the, involvement, of, hormone, levels])]). relacion([sujeto(['This', biologic, 'process-based', analysis]), verbo([suggests]), complemento([candidate, susceptibility, markers, and, supports, the, theory, that, disrupted, hormone, regulation, plays, a, role, in, bladder, carcinogenesis])]). relacion([sujeto(['Leucocyte', counts, and, a, broad, range, of, inflammatory, serum, proteins, were, analysed, to]), verbo([gain]), complemento([insight, into, the, systemic, alterations])]). relacion([sujeto(['This', was, accompanied, by, an]), verbo([increase]), complemento([of, the, 'inflammation-related', serum, proteins, 'GPNMB,', 'MST1', and, 'TRADD'])]). relacion([sujeto(['In', 'parallel,', ustekinumab]), verbo([modulates]), complemento([important, circulating, 'inflammation-related', proteins])]). relacion([sujeto(['Most', are, 'single-site', and, not, 'longitudinal,', and, these]), verbo([have]), complemento([not, identified, a, means, for, early, prediction, of, outcomes])]). relacion([sujeto(['Children', aged, 3, to, 15, months, were, enrolled, in, an, observational, study, with, either, '(', 1, ')', a, convincing, history, of, egg, 'allergy,', milk, 'allergy,', or, both, with, a, positive, skin, prick, test, '(', 'SPT)', response, to, the]), verbo([trigger]), complemento([food, 'and/or', '(', 2, ')', 'moderate-to-severe', atopic, dermatitis, '(', 'AD)', and, a, positive, 'SPT', response, to, milk, or, egg])]). relacion([sujeto(['Milk', allergy]), verbo([has]), complemento([resolved, in, 154, '(', 52.6, '%', ')', subjects, at, a, median, age, of, 63, months, and, a, median, age, at, last, 'follow-up', of, 66, months])]). relacion([sujeto(['Expression', of, 'GATA-3', in, female, breast, cancers]), verbo([has]), complemento([been, linked, to, estrogen, receptor, '(', 'ER)', expression, 'and,', in, 'turn,', to, improved, outcomes])]). relacion([sujeto(['However,', 'GATA-3']), verbo([has]), complemento([not, been, studied, in, male, breast, cancers])]). relacion([sujeto(['GATA-3', is]), verbo([expressed]), complemento([less, often, in, male, than, female, breast, cancers])]). relacion([sujeto(['DNAzymes', are, 'single-stranded', catalytic, 'DNA', molecules, that]), verbo([bind]), complemento([and, cleave, specific, sequences, in, a, target, mRNA, molecule])]). relacion([sujeto(['Their', potential, as, novel, therapeutic, agents]), verbo([has]), complemento([been, demonstrated, in, a, variety, of, disease, models])]). relacion([sujeto(['However,', no, studies]), verbo([have]), complemento([yet, addressed, their, toxicology, and, safety, pharmacology, profiles, in, detail])]). relacion([sujeto(['In', mouse, 'embryos,', segregation, of, the, inner, cell, mass, '(', 'ICM)', and, trophectoderm, '(', 'TE)', lineages, is]), verbo([regulated]), complemento([by, 'genes,', such, as, 'OCT-4,', 'CDX2', and, 'TEAD4'])]). relacion([sujeto(['However,', the, molecular, mechanisms, that]), verbo([regulate]), complemento([the, segregation, of, the, 'ICM', and, 'TE', lineages, in, porcine, embryos, remain, unknown])]). relacion([sujeto(['In', elongated, 'embryos,', 'OCT-4,', 'NANOG,', 'FGF4', and, 'FGFR1-IIIc', were, abundantly]), verbo([expressed]), complemento([in, the, embryo, disc, '(', 'ED;', 'ICM', 'lineage),', but, their, expression, levels, were, very, low, in, the, 'TE'])]). relacion([sujeto(['The', 'Th2', locus, control, region, '(', 'LCR)']), verbo([has]), complemento([been, shown, to, be, important, in, efficient, and, coordinated, cytokine, gene, regulation, during, 'Th2', cell, differentiation])]). relacion([sujeto(['To', study, the, molecular, mechanism, of, the, 'Th2', 'LCR,', we, searched, for, proteins]), verbo([binding]), complemento([to, it])]). relacion([sujeto(['We', discovered, that, transcription, factor, 'YY1']), verbo([bound]), complemento([to, the, 'LCR', and, the, entire, 'Th2', cytokine, locus, in, a, 'Th2-specific', manner])]). relacion([sujeto(['Retroviral', overexpression, of, 'YY1']), verbo([induced]), complemento(['Th2', cytokine, expression])]). relacion([sujeto(['CD4-specific', knockdown, of, 'YY1', in, mice]), verbo([caused]), complemento([marked, reduction, in, 'Th2', cytokine, 'expression,', repressed, chromatin, 'remodeling,', decreased, intrachromosomal, 'interactions,', and, resistance, in, an, animal, model, of, asthma])]). relacion([sujeto(['YY1', physically]), verbo([associated]), complemento([with, 'GATA-binding', 'protein-3', '(', 'GATA3)', and, is, required, for, 'GATA3', binding, to, the, locus])]). relacion([sujeto(['YY1']), verbo([bound]), complemento([to, the, regulatory, elements, in, the, locus, before, 'GATA3', binding])]). relacion([sujeto(['Thus,', 'YY1', cooperates, with, 'GATA3', and, is]), verbo([required]), complemento([for, regulation, of, the, 'Th2', cytokine, locus, and, 'Th2', cell, differentiation])]). relacion([sujeto(['T-bet', plays, an, important, role, in, 'immunoregulation;', it]), verbo([induces]), complemento([the, differentiation, of, 'Th1', together, with, the, homeobox, transcription, factor, gene, 'Hlx'])]). relacion([sujeto(['Recent', studies, show, that, 'T-bet', and, 'Th1-associated', factors, are, critical, in]), verbo([regulating]), complemento([tumor, development])]). relacion([sujeto(['These', results]), verbo([suggested]), complemento([that, the, decreased, 'Hlx', expression, was, closely, associated, with, 'T-bet', and, 'Runx3', downregulations, and, may, contribute, to, the, development, of, gastric, cancer])]). relacion([sujeto(['Other', injured, tissues, like, the, heart, and, the, fin, also, upregulate, 'Gata3', in, response, to, 'injury,']), verbo([suggesting]), complemento([that, 'Gata3', is, a, general, response, to, tissue, damage])]). relacion([sujeto(['T-bet', and, 'GATA3']), verbo([regulate]), complemento([the, 'CD4+', 'T', cell, 'Th1/Th2', cell, fate, decision, but, little, is, known, about, the, interplay, between, these, factors, outside, of, the, murine, 'Ifng', and, 'Il4/Il5/Il13', loci])]). relacion([sujeto(['Here', we, show, that, 'T-bet', and, 'GATA3']), verbo([bind]), complemento([to, multiple, distal, sites, at, immune, regulatory, genes, in, human, effector, 'T', cells])]). relacion([sujeto(['These', sites, display, markers, of, functional, 'elements,']), verbo([act]), complemento([as, enhancers, in, reporter, assays, and, are, associated, with, a, requirement, for, 'T-bet', and, 'GATA3'])]). relacion([sujeto(['Furthermore,', we, demonstrate, that, both, factors]), verbo([bind]), complemento([distal, sites, at, 'Tbx21', and, that, 'T-bet', directly, activates, its, own, expression])]). relacion([sujeto(['We', also, show, that, in, 'Th1', 'cells,', 'GATA3', is, distributed, away, from, 'Th2', 'genes,', instead, occupying, 'T-bet']), verbo([binding]), complemento([sites, at, 'Th1', 'genes,', and, that, 'T-bet', is, sufficient, to, induce, 'GATA3', binding, at, these, sites])]). relacion([sujeto(['GATA-3,', a, 'C2C2-type', zinc, finger, transcription, 'factor,']), verbo([regulates]), complemento([many, steps, of, 'T', cell, development, and, differentiation])]). relacion([sujeto(['It', is, also]), verbo([required]), complemento([for, optimal, production, of, type, 2, cytokines, by, 'CD8(+)', 'T', cells])]). relacion([sujeto(['In', this, 'paper,', we]), verbo([report]), complemento([that, 'GATA-3', is, required, for, 'MHC-mediated', positive, selection, and, final, maturation, of, 'CD8', 'single-positive', thymocytes])]). relacion([sujeto(['Deficiency', of, 'GATA-3']), verbo([mediated]), complemento([by, a, 'CD4cre', transgene, led, to, 'age-dependent', lymphadenopathy, partly, because, of, abnormal, expansion, of, 'CD8(+)', 'T', cells, driven, by, a, 'cell-extrinsic', mechanism])]). relacion([sujeto(['The', analysis, of, 'Fgf10', mouse, mutants]), verbo([has]), complemento([demonstrated, a, critical, role, for, this, ligand, in, neurosensory, development, of, the, vertebrate, inner, 'ear,', and, we, have, been, looking, to, define, the, direct, upstream, regulators, of, 'Fgf10', in, this, sensory, 'organ,', as, part, of, constructing, the, programme, of, early, inner, ear, development])]). relacion([sujeto(['Through', the, analysis, of, reporter, constructs, in, transgenic, mouse, embryos, and, neonatal, 'mice,', in, this]), verbo([report]), complemento([we, define, a, minimal, 1400, bp, enhancer, from, the, 5, '\'', flanking, region, of, 'Fgf10'])]). relacion([sujeto(['This', regulatory, region, includes, three, putative, 'Gata3']), verbo([binding]), complemento([sites, that, we, demonstrate, directly, interacts, with, 'Gata3', protein, through, the, 'DNA', binding, domain, with, differing, affinities])]). relacion([sujeto(['Site', directed, mutagenesis, of, all, three, sites, and, functional, testing, in, transgenic, embryos, using, reporter, transgenes]), verbo([reveals]), complemento([an, absolute, requirement, for, 'Gata3', in, controlling, 'Fgf10', expression])]). relacion([sujeto(['Transgenic', analysis, of, individual, 'Gata3']), verbo([binding]), complemento([site, mutations, illustrates, that, only, one, of, these, binding, sites, is, necessary, for, reporter, expression])]). relacion([sujeto(['Together', these, data, demonstrate, that, 'Gata3', directly]), verbo([activates]), complemento(['Fgf10', in, the, early, inner, 'ear,', and, does, so, through, a, single, binding, site])]). relacion([sujeto(['Hypoparathyroidism,', sensorineural, deafness, and, renal, dysplasia, '(', 'HDR)', syndrome, '(', 'MIM', 146255, ')', is, a, rare, autosomal, dominant, disorder]), verbo([caused]), complemento([by, mutations, in, the, gene, encoding, 'GATA3,', a, dual, 'zinc-finger', transcription, factor, involved, in, vertebrate, embryonic, development])]). relacion([sujeto(['In', this, clinical, case, study, we]), verbo([report]), complemento([on, a, 'follow-up', of, a, phenotype, associated, with, a, 'GATA3', mutation])]). relacion([sujeto(['By', the, age, of, 7, 'years,', growth, is, 'age-appropriate,', severe, bilateral, hearing]), verbo([loss]), complemento(['(', dB, 60, ')', was, corrected, by, hearing, aids])]). relacion([sujeto(['In', 'conclusion,', a, mildly, impaired, clinical, course, was, achieved, by, the, age, of, 7, years, in, a, patient, with, 'HDR', 'syndrome;', this]), verbo([report]), complemento([adds, to, the, body, of, data, on, 'genotype-phenotype', analysis, in, 'HDR', syndrome])]). relacion([sujeto([·, 'Allergic', asthma, is, a, chronic, airway, disorder, characterized, by, airway, hyperresponsiveness, to, 'allergens,', chronic, airway, 'inflammation,', airway, 'edema,']), verbo([increased]), complemento([mucus, 'secretion,', excess, production, of, 'Th2', 'cytokines,', and, eosinophil, accumulation, in, the, lungs])]). relacion([sujeto(['To', investigate, the, 'anti-asthmatic', effects, and, mechanism, of, ursolic, 'acid,', we, studied, the, development, of, pulmonary, eosinophilic, inflammation, and]), verbo([enhanced]), complemento([pause, '(', 'Penh)', in, a, mouse, model, of, allergic, asthma])]). relacion([sujeto(['In', 'BALB/c', 'mice,', ursolic, acid, had]), verbo([suppressed]), complemento([eosinophil, 'infiltration,', allergic, airway, 'inflammation,', and, 'Penh,', which, occurred, by, suppressing, the, production, of, 'IL-5,', 'IL-13,', 'IL-17,', and, 'ovalbumin-specific', 'IgE', by, blocking, the, 'GATA-3', and, 'STAT6', pathways])]). relacion([sujeto(['Our', data]), verbo([suggest]), complemento([the, therapeutic, mechanism, of, ursolic, acid, in, asthma, is, based, on, reductions, of, 'Th2', cytokines, '(', 'IL-5', and, 'IL-13),', 'ovalbumin-specific', 'IgE', 'production,', and, eosinophil, infiltration, via, the, 'Th2-GATA-3,', 'STAT6,', and, 'IL-17-NF-κB', pathways])]). relacion([sujeto(['This', study, investigated, whether, an, imbalance, in, 'Th1/Th2', cells, is]), verbo([involved]), complemento([in, the, 'post-resuscitation', myocardial, immune, dysfunction])]). relacion([sujeto([26, 'Wuzhishan', miniature, pigs, were, randomly, divided, into, return, of, spontaneous, circulation, '(', 'ROSC)', group, '(', 'n=20)', and, 'sham-operated', group, '(', 'n=6),', 20, pigs, were, subjected, to, 8, min, of, electrically]), verbo([induced]), complemento([cardiac, 'arrest,', 'After', successful, 'ROSC,', the, 16, surviving, pigs, were, randomly, assigned, to, be, sacrificed, '(', 'n=8', per, 'group)', at, 12, and, 24, h, after, 'ROSC,', respectively])]). relacion([sujeto(['The', levels, of, myocardium, 'IFN-γ', were, markedly, 'increased,', while, 'IL-4', was, significantly]), verbo([decreased]), complemento([in, the, 'post-ROSC', group, compared, with, the, 'sham-operated', group, '(', 'P<0'])]). relacion([sujeto(['Protein', expression, and, mRNA, levels, of, 'T-bet', were, markedly]), verbo([increased]), complemento([in, the, myocardium, of, pigs, in, the, 'post-ROSC', group, compared, with, the, 'sham-operated', group, '(', 'P<0'])]). relacion([sujeto(['The', myocardial, immune, dysfunction]), verbo([induced]), complemento([by, the, change, in, expression, levels, of, the, transcription, factors, 'GATA-3', and, 'T-bet', may, be, involved, in, the, process, of, 'post-resuscitation', myocardial, injury, in, a, porcine, model, of, cardiac, arrest])]). relacion([sujeto(['A', transcription, factor, 'ELISA', was, used, for, differential]), verbo([binding]), complemento([of, 'GATA', proteins, to, the, variant, region])]). relacion([sujeto(['Four', polymorphisms, 'SCCA1', promoter, that, were, in, linkage, disequilibrium, were]), verbo([associated]), complemento([with, skin, test, positivity, in, asthmatic, children, and, showed, higher, promoter, activity, and, higher, binding, of, 'GATA-2', and, 'GATA-3', after, 'IL-4 + IL-13', stimulation])]). relacion([sujeto(['IL-6,', 'IL-8', levels, were, significantly, higher, in, cells, transfected, with, 'SCCA1', whereas, 'RANTES']), verbo([increased]), complemento([only, after, 'IL-4', stimulation])]). relacion([sujeto(['Transfection', of, 'A549', cells, with, 'SCCA1', resulted, in]), verbo([decreased]), complemento(['MUC5AC', expression, and, conferred, protection, against, apoptosis])]). relacion([sujeto(['Our', results, showed, that, 'SCCA1']), verbo([has]), complemento([diverse, effects, on, many, of, the, cellular, events, that, characterize, asthma, and, its, role, extends, beyond, protease, inhibition])]). relacion([sujeto(['Abstract', 'Background:', 'To', detect, genes]), verbo([associated]), complemento([with, the, expression, of, 'ESR1', and, 'PGR', -, as, well, as, of, their, protein, 'products,', estrogen, receptor, '(', 'ER)', and, progesterone, receptor, '(', 'PR)', -, 221, 'de-identified', invasive, ductal, carcinomas, of, the, breast, were, investigated])]). relacion([sujeto(['Our', 'long-term', goal, is, to, decipher, relationships, between, the, expression, of, 'ER-', and, 'PR-associated', genes, and, breast, cancer, behavior, to, improve, diagnostics, and, identify, new, molecular]), verbo([targets]), complemento([for, drug, design])]). relacion([sujeto(['ER', and, 'PR', protein, levels, were, quantified, by, either, enzyme, immunoassay, or, 'radio-ligand']), verbo([binding]), complemento([assay])]). relacion([sujeto(['Total', 'RNA', preparations, were, reverse]), verbo([transcribed]), complemento([for, qPCR, measurements, of, 'ESR1,', 'PGR', and, 31, gene, candidates])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, direct, relationships, of, these, genes, exist, with, estrogen, and, progestin, receptor, mediated, pathways])]). relacion([sujeto(['Pathway', analysis, software]), verbo([provided]), complemento([additional, evidence, of, gene, interactions])]). relacion([sujeto(['Hypoparathyroidism,', 'deafness,', and, renal, dysplasia, '(', 'HDR)', syndrome, is, an, autosomal, dominant, disorder]), verbo([caused]), complemento([by, a, 'GATA3', gene, mutation])]). relacion([sujeto(['Here', we]), verbo([report]), complemento([a, novel, mutation, of, 'GATA3', in, a, patient, diagnosed, with, 'HDR', syndrome, at, the, age, of, 58, with, extensive, intracranial, calcification])]). relacion([sujeto(['The', 'S198X', mutation]), verbo([leads]), complemento([to, a, loss, of, two, zinc, finger, deoxyribonucleic, acid, '(', 'DNA)', binding, domains, and, is, considered, to, be, responsible, for, 'HDR', syndrome])]). relacion([sujeto(['Minocycline', protects, against, asthma, independently, of, its, antibiotic, function, and, was, recently]), verbo([reported]), complemento([as, a, potent, 'poly(ADP-ribose)', polymerase, '(', 'PARP)', inhibitor])]). relacion([sujeto(['In', an, animal, model, of, 'asthma,', a, single, administration, of, minocycline]), verbo([conferred]), complemento([excellent, protection, against, 'ovalbumin-induced', airway, 'eosinophilia,', mucus, 'hypersecretion,', and, 'Th2', cytokine, production, '(', 'IL-4/IL-5/IL-12(p70)/IL-13/GM-CSF)', and, a, partial, protection, against, airway, hyperresponsiveness])]). relacion([sujeto(['A', reduction, in, 'poly(ADP-ribose)', immunoreactivity, in, the, lungs, of, 'minocycline-treated/ovalbumin-challenged', mice, correlated, with]), verbo([decreased]), complemento([oxidative, 'DNA', damage])]). relacion([sujeto(['Minocycline', blocked, 'allergen-specific', 'IgE', production, in, 'B', cells, potentially, by]), verbo([modulating]), complemento(['T', cell, receptor, '(', 'TCR)-linked', 'IL-4', production, at, the, mRNA, level, but, not, through, a, modulation, of, the, 'IL-4-JAK-STAT-6', 'axis,', 'IL-2', 'production,', or, 'NFAT1', activation])]). relacion([sujeto(['Interestingly,', the, drug]), verbo([promoted]), complemento([a, slightly, higher, 'Src', and, 'ERK1/2', phosphorylation])]). relacion([sujeto(['These', results, show, a, potentially, broad, effect, of, minocycline, but, that, it, may, block, 'IgE', production, in, part, by]), verbo([modulating]), complemento(['TCR', 'function,', particularly, by, inhibiting, the, signaling, 'pathway,', leading, to, 'NF-κB', 'activation,', 'GATA-3', 'expression,', and, subsequent, 'IL-4', production])]). relacion([sujeto(['These', 'bulk-cultured', 'T', cells]), verbo([expressed]), complemento([transcripts, for, both, 'T', helper, 1, cells, '(', 'Th1)', master, regulator, '(', 'T-bet)', and, 'T', helper, 2, cells, '(', 'Th2)', master, regulator, '(', 'GATA-3)'])]). relacion([sujeto(['These', clones]), verbo([expressed]), complemento([both, 'TCRα', and, 'TCRβ,', but, could, not, produce, a, 'TCRγδ', heterodimer, since, they, typically, only, expressed, either, 'TCRγ', or, 'TCRδ'])]). relacion([sujeto(['These', clones, also]), verbo([expressed]), complemento([the, 'TCR', 'co-receptor', genes, 'CD4-1', or, 'CD4-2,', whereas, they, did, not, express, 'CD8α', or, 'CD8β'])]). relacion([sujeto(['In', 'addition,', 'GATA-3', was]), verbo([expressed]), complemento([whereas, 'T-bet', was, not])]). relacion([sujeto(['To', characterize, the, 'KoThL5', cells, by, their, cytokine, production, 'profile,', they, were]), verbo([stimulated]), complemento([with, 'PHA', and, investigated, by, 'real-time', 'RT-PCR'])]). relacion([sujeto([mRNA, expression, of, 'Th2-related', cytokine, '(', 'IL-4/13B)', was, only]), verbo([enhanced]), complemento([in, 'KoThL5', cells, whereas, both, 'Th1-related', cytokine, '(', 'IFNγ)', and, 'Th2-related', cytokines, '(', 'IL-4/13A', and, 'IL-4/13B)', were, significantly, enhanced, in, 'bulk-cultured', 'T', cells])]). relacion([sujeto(['The', 'KoThL5', cell, line]), verbo([has]), complemento([considerable, potential, for, addressing, questions, concerning, the, properties, of, teleost, 'Th2', cells])]). relacion([sujeto(['We']), verbo([have]), complemento([recently, developed, a, highly, efficient, mouse, dominant, negative, 'IL-4/IL-13', 'DNA', 'vaccine,', which, blocks, both, 'IL-4', and, 'IL-13', signal, 'transductions,', resulting, in, the, amelioration, of, atopic, reaction])]). relacion([sujeto(['At', the, next, 'step,', the, further, consistent, protein, supplementation, system, is]), verbo([required]), complemento([for, stable, suppression, of, allergic, reaction])]). relacion([sujeto(['The', 'anti-inflammatory', function, was, evaluated, measuring, ear, thickness, and, analyzing, histological, change, in, mice, 'AD', model]), verbo([induced]), complemento([by, repeated, elicitation, of, oxazolone])]). relacion([sujeto(['In', 'IL-4DM,', ear, thickness, was]), verbo([suppressed]), complemento([significantly, in, the, early, phase, of, the, elicitation, schedule, of, contact, hypersensitivity, response])]). relacion([sujeto(['In', 'IL-4DM-skin-grafted', 'mice,', the, inflammatory, response, was]), verbo([suppressed]), complemento([significantly, similarly, in, the, early, phase, accompanied, with, lesional, suppressed, 'Th2-type-cytokine', signaling, transduction])]). relacion([sujeto(['IL-4DM', skin]), verbo([has]), complemento([the, 'anti-inflammatory', function, especially, in, the, acute, phase, of, 'AD'])]). relacion([sujeto(['Using', immunohistochemistry, it, could, be, shown, that, the, tumor, cells]), verbo([expressed]), complemento([cytokeratin, 7, '(', 'CK7),', estrogen, receptors, and, 'Gata', 3, but, not, 'CK20', or, 'Cdx2'])]). relacion([sujeto(['Signaling', pathways, are, intimately]), verbo([involved]), complemento([in, cellular, 'differentiation,', allowing, cells, to, respond, to, their, environment, by, regulating, gene, expression])]). relacion([sujeto(['Although', enhancers, are]), verbo([recognized]), complemento([as, key, elements, that, regulate, selective, gene, 'expression,', the, interplay, between, signaling, pathways, and, actively, used, enhancer, elements, is, not, clear])]). relacion([sujeto(['Our', data, establish, that, 'STAT', proteins]), verbo([have]), complemento([a, major, impact, on, the, activation, of, 'lineage-specific', enhancers, and, the, suppression, of, enhancers, associated, with, alternative, cell, fates])]). relacion([sujeto(['Transcriptome', analysis, further, supports, a, functional, role, for, enhancers]), verbo([regulated]), complemento([by, 'STATs'])]). relacion([sujeto(['Glucocorticoid', receptor, '(', 'GR)', variants]), verbo([have]), complemento([been, found, to, be, associated, with, 'stress-related', disorders])]). relacion([sujeto(['FoxP3', mRNA, was, significantly, altered, in, the, 'BclI', 'WT', '(']), verbo([decreased]), complemento([at, 24, h, and, increased, at, 11, 'days)', but, not, in, the, 'GG', allele])]). relacion([sujeto(['The', expression, of, 'β-2', adrenergic, receptor, '(', 'β2AR)', was]), verbo([increased]), complemento([at, 24, h, in, both, 'CC', and, 'GG', alleles, '(', 'P', &, 'lt;', 0.01, and, 'P', &, 'lt;', 0.001, ')', ',', but, decreased, significantly, at, 11, days, in, only, 'GG', alleles])]). relacion([sujeto(['Estrogen', receptor, '(', 'ESR1)', drives, growth, in, the, majority, of, human, breast, cancers, by]), verbo([binding]), complemento([to, regulatory, elements, and, inducing, transcription, events, that, promote, tumor, growth])]). relacion([sujeto(['In', order, to, investigate, the, composition, of, enhancers]), verbo([involved]), complemento([in, 'estrogen-induced', transcription, and, the, potential, role, of, 'GATA3,', we, performed, extensive, 'ChIP-sequencing', in, unstimulated, breast, cancer, cells, and, following, estrogen, treatment])]). relacion([sujeto(['We']), verbo([find]), complemento([that, 'GATA3', is, pivotal, in, mediating, enhancer, accessibility, at, regulatory, regions, involved, in, 'ESR1-mediated', transcription])]). relacion([sujeto(['These', global, genomic, changes, altered, the, 'ESR1-binding', profile, that, subsequently, occurred, following, 'estrogen,', with, events, exhibiting, both]), verbo([loss]), complemento([and, gain, in, binding, 'affinity,', implying, a, 'GATA3-mediated', redistribution, of, 'ESR1', binding])]). relacion([sujeto(['Chromatin', loops, at, the, 'TFF', locus]), verbo([involving]), complemento(['ESR1-bound', enhancers, occurred, independently, of, 'ESR1', when, 'GATA3', was, 'silenced,', indicating, that, 'GATA3,', when, present, on, the, 'chromatin,', may, serve, as, a, licensing, factor, for, 'estrogen-ESR1-mediated', interactions, between, 'cis-regulatory', elements])]). relacion([sujeto(['Together,', these, experiments]), verbo([suggest]), complemento([that, 'GATA3', directly, impacts, 'ESR1', enhancer, 'accessibility,', and, may, potentially, explain, the, contribution, of, 'mutant-GATA3', in, the, heterogeneity, of, 'ESR1+', breast, cancer])]). relacion([sujeto(['Here', we, identify, one, such, 'gene-the', transcription, factor, 'gata3-which', is]), verbo([expressed]), complemento([only, after, injury, in, different, zebrafish, organs])]). relacion([sujeto(['Gata3', is]), verbo([required]), complemento([for, reactive, proliferation, of, radial, glia, 'cells,', subsequent, regenerative, 'neurogenesis,', and, migration, of, the, newborn, neurons])]). relacion([sujeto(['We']), verbo([found]), complemento([that, these, 'regeneration-specific', roles, of, 'Gata3', are, dependent, on, the, injury, because, 'Gata3', overexpression, in, the, unlesioned, adult, zebrafish, brain, is, not, sufficient, to, induce, neurogenesis])]). relacion([sujeto(['Thus,', gata3]), verbo([acts]), complemento([as, a, specific, 'injury-induced', proregenerative, factor, that, is, essential, for, the, regenerative, capacity, in, vertebrates])]). relacion([sujeto(['Allergic', asthma, is]), verbo([associated]), complemento([with, 'Th2-mediated', inflammation])]). relacion([sujeto(['The', aim, of, this, investigation, was, to, determine, whether, 'Glycyrrhiza', uralensis, flavonoids]), verbo([have]), complemento([inhibitory, effects, on, memory, 'Th2', responses, in, vitro, and, 'antigen-induced', 'Th2', inflammation, in, vivo])]). relacion([sujeto(['Isoliquiritigenin,', 7, ',', 4, '\'', -, dihydroxyflavone, '(', 7, ',', 4, '\'', -, 'DHF)', and, liquiritigenin, significantly]), verbo([suppressed]), complemento(['IL-4', and, 'IL-5', production, in, a, 'dose-dependent', 'manner,', 7, ',', 4, '\'', -, 'DHF', being, most, potent])]). relacion([sujeto(['It', was, also, evaluated, for, effects, on, 'D10', cell, 'proliferation,', 'GATA-3', expression, and, 'IL-4', mRNA, 'expression,', which, were, 'suppressed,', with, no]), verbo([loss]), complemento([of, cell, viability])]). relacion([sujeto(['Chronic', treatment, with, 7, ',', 4, '\'', -, 'DHF', in, a, murine, model, of, allergic, asthma, not, only, significantly, reduced, eosinophilic, pulmonary, 'inflammation,', serum, 'IgE', 'levels,', 'IL-4', and, 'IL-13', 'levels,', but, also]), verbo([increased]), complemento(['IFN-γ', production, in, lung, cell, cultures, in, response, to, antigen, stimulation])]). relacion([sujeto(['Conditioned', media]), verbo([induced]), complemento([the, expression, of, otic, progenitor, markers, 'PAX8,', 'PAX2,', 'GATA3', and, 'SOX2'])]). relacion([sujeto(['Inhibition', of, 'WNT', signaling]), verbo([prevented]), complemento([differentiation, into, otic, 'progenitors,', while, 'WNT', activation, partially, phenocopied, results, seen, with, the, conditioned, media])]). relacion([sujeto(['This', study, demonstrates, that, hMSCs, can, be, driven, to]), verbo([express]), complemento([key, genes, found, in, the, otic, lineages, and, thereby, promotes, their, status, as, candidates, for, regenerative, therapies, for, deafness])]). relacion([sujeto(['Loricrin', is, a, major, component, of, the, epidermal, cornified, cell, envelope, and, is]), verbo([expressed]), complemento([only, in, terminally, differentiated, keratinocytes])]). relacion([sujeto(['This', cell, 'differentiation-specific', expression, pattern]), verbo([suggests]), complemento([specific, regulatory, mechanisms, for, activation, of, loricrin, gene, transcription, in, differentiated, keratinocytes])]). relacion([sujeto(['Here,', we, identified, a, positive, regulatory, element, in, the, proximal, promoter, region, of, the, loricrin, gene]), verbo([involved]), complemento([in, activation, of, its, expression, in, differentiated, keratinocytes])]). relacion([sujeto(['A', database, search, indicated, that, this, sequence, contained, a, 'GATA-3']), verbo([binding]), complemento([motif])]). relacion([sujeto(['Constructs', with, point, mutations, in, the, 'GATA-3']), verbo([binding]), complemento([motif, showed, decreased, reporter, 'activity,', indicating, that, 'GATA-3', positively, regulates, loricrin, gene, transcription])]). relacion([sujeto(['Cotransfection', experiments, indicated, that, 'GATA-3']), verbo([activates]), complemento([transcription, of, the, loricrin, gene, in, a, cooperative, manner, with, 'c-Fos', and, 'Sp1'])]). relacion([sujeto(['The', 'co-infection', of, 'HIV', and, helminth, 'parasites,', such, as, 'Schistosoma', 'spp,']), verbo([has]), complemento([increased, in, 'sub-Saharan', 'Africa'])]). relacion([sujeto(['Many', 'HIV', vaccine, candidate, studies]), verbo([have]), complemento([been, completed, or, are, in, ongoing, clinical, 'trials,', but, it, is, not, clear, how, 'HIV', vaccines, might, affect, the, course, of, schistosome, infections])]). relacion([sujeto(['Using', this, 'model,', we]), verbo([found]), complemento([that, 'Th2', 'cytokines,', such, as, 'IL-4', and, 'IL-13,', were, highly, induced, after, schistosome, infection])]). relacion([sujeto(['Treatment', of, infected, mice, with, the, 'HIV', 'DNA', vaccine, resulted, in, a, significant, attenuation, of, this, rise, in, 'IL-13', expression, and, an]), verbo([increase]), complemento([in, expression, of, the, 'Th1', 'cytokine,', 'TNF-α'])]). relacion([sujeto(['Interestingly,', the, 'IL-4', '(', +, ')', 'IFN-γ', '(', +, ')', phenotype, appears, in, 'schistosome-infected', mice, that, received, 'HIV', 'vaccination,', and, is]), verbo([associated]), complemento([with, the, expression, of, transcription, factors, 'GATA3', '(', +, ')', 'T-bet', '(', +, ')', in, these, mice])]). relacion([sujeto(['These', studies, indicate, that, 'DNA', vaccination, can]), verbo([have]), complemento([an, impact, on, ongoing, chronic, infection])]). relacion([sujeto(['To', address, whether, 'Tregs', and, 'FoxP3,', a, transcription, factor]), verbo([required]), complemento([for, 'Treg', 'function,', similarly, influence, progression, rates, of, 'ALS', 'patients,', 'T-lymphocytes', from, patients, were, assessed, by, flow, cytometry])]). relacion([sujeto(['No', differences, in, 'IL10,', 'Tbx21,', a, 'Th1', transcription, factor, or, 'IFN-γ', expression, were]), verbo([found]), complemento([between, slow, and, rapidly, progressing, patients])]). relacion([sujeto(['Collectively,', these, data]), verbo([suggest]), complemento([that, 'Tregs', and, 'Th2', lymphocytes, influence, disease, progression, rates])]). relacion([sujeto(['GATA', transcription, factors]), verbo([regulate]), complemento([transcription, during, development, and, differentiation, by, recognizing, distinct, 'GATA', sites, with, a, tandem, of, two, conserved, zinc, 'fingers,', and, by, mediating, 'long-range', 'DNA', looping])]). relacion([sujeto(['In', one, 'structure,', both, zinc, fingers, wrap, around, a, palindromic, 'GATA', 'site,', cooperatively]), verbo([enhancing]), complemento([the, binding, affinity, and, kinetic, stability])]). relacion([sujeto(['Strikingly,', in, the, other, two, 'structures,', the, two, fingers, of, 'GATA', 'DBD']), verbo([bind]), complemento(['GATA', sites, on, different, 'DNA', 'molecules,', thereby, bridging, two, separate, 'DNA', fragments])]). relacion([sujeto(['These', findings, not, only]), verbo([provide]), complemento([insights, into, the, structure, and, function, of, 'GATA', proteins, but, also, shed, light, on, the, molecular, basis, of, 'long-range', gene, regulation])]). relacion([sujeto(['The', 'ICM', and, 'TE', were, isolated, from, blastocysts, harvested, at, day, 8, after, insemination, by, magnetic]), verbo([activated]), complemento([cell, 'sorting,', and, cDNA, sequenced, using, the, 'SOLiD', 4.0, system])]). relacion([sujeto(['A', total, of, 870, genes, were, differentially]), verbo([expressed]), complemento([between, 'ICM', and, 'TE'])]). relacion([sujeto(['Kinases']), verbo([have]), complemento([been, implicated, in, the, immunopathological, mechanisms, of, 'Systemic', 'Lupus', 'Erythematosus', '(', 'SLE)'])]). relacion([sujeto(['MAPK1', expression, correlated, with, 'Th1-(IL-12A,', 'T-box', 'TF-(T-bet)),', 'Th2-(GATA']), verbo([binding]), complemento(['protein-(GATA)-3),', and, 'IL-10', expressions])]). relacion([sujeto(['IL-10', expression, was]), verbo([increased]), complemento([and, correlated, with, plasma, 'Tumor', 'Necrosis', 'Factor', '(', 'TNF)-α', and, 'Th0-(IL-2),', 'Th1-(IL-12A,', 'T-bet),', 'GATA3,', 'Treg-(Forkhead/winged-helix', transcription, 'factor-', '(', 'FOXP)-3),', and, 'IL-6', expressions])]). relacion([sujeto(['Conclusion,', 'SLE', patients, presented, a, systemic, immunoinflammatory, 'activity,', augmented, 'AKT1', and, 'MAPK1', 'expressions,', proinflammatory, 'cytokines,', and, 'Calprotectin,', together, with]), verbo([increased]), complemento([expression, of, 'Treg-related', 'genes,', suggesting, a, regulatory, feedback, opposing, the, inflammatory, activity])]). relacion([sujeto(['Epidemiologic', studies]), verbo([have]), complemento([reported, the, association, between, fine, particles, '(', aerodynamic, diameter, '≤', 2.5, 'μm;', 'PM2'])]). relacion([sujeto(['To', investigate, the, dose, and, 'time-dependent', role, of, 'toll-like', receptor, '(', 'TLR)', and, 'Th1/Th2', shift, in, local, and, systemic, inflammation]), verbo([induced]), complemento([by, 'PM2'])]). relacion([sujeto(['Inflammatory', infiltration, and, macrophages, with, engulfed, particles, were]), verbo([found]), complemento([by, lung, histopathology, after, 'PM2'])]). relacion([sujeto(['TLR4', positive, cells]), verbo([decreased]), complemento([in, 'BALF', but, increased, in, blood, at, 24, h, after, the, exposure])]). relacion([sujeto(['The', low, percentage, of, 'TLR4', positive, cells, continued, to, day, 14, in, 'BALF,', but, recovered, at, day, 7, and]), verbo([decreased]), complemento([further, to, lower, than, the, control, value, at, day, 14, in, blood])]). relacion([sujeto(['In', 'BALF', at, 24, h, after, the, 'exposure,', the, 'Th2', related, cytokines, 'IL-5', and, 'IL-10']), verbo([increased]), complemento(['dose-dependently;', and, in, 'blood,', the, 'Th2', related, cytokines, 'IL-4,', 'IL-5,', and, 'IL-10', also, increased])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, acute, exposure, of, 'PM2'])]). relacion([sujeto([5]), verbo([leads]), complemento([to, acute, inflammatory, responses, locally, and, systemically, in, mice])]). relacion([sujeto(['TLR2', and, 'TLR4', are]), verbo([involved]), complemento([in, this, process, and, 'PM2'])]). relacion([sujeto(['The', putative, primary, structure, of, the, polypeptide, deduced, from, the, cDNA, sequence, of, grass, carp, 'T-bet', contained, 608, 'aa,', which, possessed, a, 'T-box', 'DNA']), verbo([binding]), complemento([domain])]). relacion([sujeto(['The', 'YxKxHxxxRP', 'motif,', 'KRRLSA', and, 'LMEKs/n', sequences, were, also]), verbo([conserved]), complemento([in, this, 'GATA-3'])]). relacion([sujeto(['RT-qPCR', results, showed, that, grass, carp, 'T-bet', gene, was, highly]), verbo([expressed]), complemento([in, head, 'kidney,', followed, by, 'spleen,', and, low, expressed, in, 'gill,', 'liver,', 'kidney,', and, 'intestine,', while, 'GATA-3', gene, was, highly, expressed, in, 'intestine,', followed, by, 'spleen,', and, low, expressed, in, 'gill,', 'liver,', 'kidney,', and, head, kidney])]). relacion([sujeto(['As', 'yet,', there, is, no, evidence, that, 'T-bet', and, 'GATA-3', '(', 'Th1/Th2', 'subsets)', are]), verbo([involved]), complemento([in, 'anti-virus', immune, of, teleost, fish])]). relacion([sujeto(['The', expression, dynamics, showed, that, three, genes, might, be, crucially]), verbo([modulated]), complemento([by, in, vivo, 'GCRV', 'infection:', '(', 1, ')', 'GCRV', mainly, induced, a, 'T-bet', expression, profile, comparing, to, the, 'GATA-3', 'expression,', while, the, higher, expression, profiles, of, 'IFN-γ', correlated, with, the, 'up-regulation', of, 'T-bet;', '(', 2, ')', 'T-bet/IFN-γ', and, 'GATA-3', expression, changes, suggest, that, in, 'GCRV-infected', grass, 'carp,', the, common, immune, state, of, head, kidney, further, 'heightens,', whereas, the, common, physiological, state, of, intestine, transforms, to, an, 'anti-virus', immune, state])]). relacion([sujeto(['From', this, 'finding,', we, realize, that, 'GCRV', mainly]), verbo([induces]), complemento([a, 'Th1', 'response,', and, 'Th1', 'cell-mediated', recognition, mechanisms, play, very, important, roles, in, 'anti-virus', cellular, immune, of, grass, carp])]). relacion([sujeto(['High-throughput', chromatin, immunoprecipitation]), verbo([has]), complemento([become, the, method, of, choice, for, identifying, genomic, regions, bound, by, a, protein])]). relacion([sujeto(['Such', regions, are, then, investigated, for, overrepresented, sequence, 'motifs,', the, assumption, being, that, they, must, correspond, to, the]), verbo([binding]), complemento([specificity, of, the, profiled, protein])]). relacion([sujeto(['However', this, approach, often, 'fails:', many]), verbo([bound]), complemento([regions, do, not, contain, the, '\'', 'expected\'', motif])]). relacion([sujeto(['This', is, because]), verbo([binding]), complemento(['DNA', directly, at, its, recognition, site, is, not, the, only, way, the, protein, can, cause, the, region, to, immunoprecipitate])]). relacion([sujeto(['Its']), verbo([binding]), complemento([specificity, can, change, through, association, with, different, 'co-factors,', it, can, bind, 'DNA', 'indirectly,', through, 'intermediaries,', or, even, enforce, its, function, through, 'long-range', chromosomal, interactions])]). relacion([sujeto(['Conventional', motif, discovery, 'methods,', though, largely, capable, of, identifying, overrepresented, motifs, from]), verbo([bound]), complemento(['regions,', lack, the, ability, to, characterize, such, diverse, modes, of, 'protein-DNA', binding, and, binding, specificities])]). relacion([sujeto(['We', present, a, novel, 'Bayesian', method, that, identifies, distinct, 'protein-DNA']), verbo([binding]), complemento([mechanisms, without, relying, on, any, motif, database])]). relacion([sujeto(['The', method, successfully, identifies, 'co-factors', of, proteins, that, do, not]), verbo([bind]), complemento(['DNA', 'directly,', such, as, mediator, and, p300])]). relacion([sujeto(['Even', for, 'well-studied', 'direct-binding', 'proteins,', this, method]), verbo([provides]), complemento([compelling, evidence, for, previously, uncharacterized, dependencies, within, positions, of, binding, 'sites,', 'long-range', chromosomal, interactions, and, dimerization])]). relacion([sujeto(['The', results, showed, that, 'miR-155', positively]), verbo([regulated]), complemento([both, 'Treg', and, 'Th17', cell, differentiation])]). relacion([sujeto(['It', also]), verbo([induced]), complemento([the, release, of, interleukin, '(', 'IL)-17A', by, 'Th17', 'cells,', but, not, the, release, of, 'IL-10', and, transforming, growth, factor, '(', 'TGF)-β1', by, 'Treg', cells])]). relacion([sujeto(['Furthermore,', we]), verbo([found]), complemento([that, 'miR-155', reacted, through, regulating, 'Janus', 'kinase/signal', transducer, and, activator, of, transcription, '(', 'JAK/STAT)', rather, than, 'TGF-β/mothers', against, decapentaplegic, homolog, '(', 'SMAD)', signaling, pathway, in, the, process, of, 'Treg', and, 'Th17', cells, differentiation])]). relacion([sujeto(['This', may, because, suppressors, of, cytokine, signaling, '(', 'SOCS)1,', the, important, negative, regulator, of, 'JAK/STAT', signaling, 'pathway,', was, the, direct]), verbo([target]), complemento([of, 'miR-155', in, this, 'process,', but, 'SMAD2', and, 'SMAD5', were, not])]). relacion([sujeto(['Therefore,', we, demonstrated, that, 'miR-155']), verbo([enhanced]), complemento(['Treg', and, 'Th17', cells, differentiation, and, 'IL-17A', production, by, targeting, 'SOCS1'])]). relacion([sujeto(['Bmp']), verbo([activates]), complemento([early, steps, for, both, fates, during, late, blastula, stage])]). relacion([sujeto(['Low', 'Bmp']), verbo([activates]), complemento([expression, of, transcription, factors, 'Tfap2a', and, 'Tfap2c', in, the, lateral, neural, 'plate,', thereby, specifying, neural, crest, fate])]). relacion([sujeto(['PPE', specification, occurs, later, at, the, end, of, gastrulation, and]), verbo([requires]), complemento([complete, attenuation, of, 'Bmp,', yet, expression, of, 'PPE', competence, factors, continues, well, past, gastrulation])]). relacion([sujeto(['Here', we, show, that, competence, factors, positively]), verbo([regulate]), complemento([each, 'other\'s', expression, during, 'gastrulation,', forming, a, 'self-sustaining', network, that, operates, independently, of, 'Bmp'])]). relacion([sujeto(['However,', 'Tfap2a', alone, is, not, sufficient, to]), verbo([activate]), complemento([any, other, competence, factors, nor, does, it, rescue, individual, placodes])]). relacion([sujeto(['On', the, other, 'hand,', misexpression, of, any, two, competence, factors, in, 'Bmp-blocked', embryos, can]), verbo([activate]), complemento([the, entire, transcription, factor, network, and, support, the, development, of, 'NC,', 'PPE', and, some, individual, placodes])]). relacion([sujeto(['We', also, show, that, while, these, factors, are, partially, redundant, with, respect, to, 'PPE', 'specification,', they, later]), verbo([provide]), complemento(['non-redundant', functions, needed, for, development, of, specific, placodes])]). relacion([sujeto(['Thus,', we]), verbo([have]), complemento([identified, a, gene, regulatory, network, that, coordinates, development, of, 'NC,', 'PPE', and, individual, placodes, in, zebrafish])]). relacion([sujeto(['Although', 'T', cell, development, is, well, characterized, using, expression, of, cell, surface, 'markers,', the, detailed, mechanisms, driving, differentiation]), verbo([have]), complemento([not, been, established])]). relacion([sujeto(['Interruption', of, 'Notch', signalling, in, partially, differentiated, cells]), verbo([increased]), complemento(['CD4', mRNA, and, protein, 'expression,', and, promoted, differentiation, to, 'CD4(+)', 'CD8(+)', 'T', cells])]). relacion([sujeto(['These', results, demonstrate, that, while, 'Notch', signalling, is, essential, for, establishment, of, the, 'T', cell, 'lineage,', at, later, stages, of, 'differentiation,', its, removal, late, in, differentiation]), verbo([promotes]), complemento([more, efficient, 'DP', cell, generation])]). relacion([sujeto(['Notch', signalling, adds, to, signals]), verbo([provided]), complemento([by, stromal, cells, to, allow, 'HSCs', to, differentiate, to, 'T', cells, via, initiation, of, transcription, factors, such, as, 'HES1,', 'GATA3', and, 'TCF7'])]). relacion([sujeto(['FCM', shows, that, 55, '%', 'CD56(+)CD16(-)CD3(-)', decidual, 'NK,', 52, '%', 'CD4(+)', 'T', cells, and, 75, '%', 'CD14(+)', monocytes]), verbo([express]), complemento(['CCR2'])]). relacion([sujeto(['Recombinant', human, 'CCL2', '(', 'rhCCL2)', and, the, decidual, stromal, cells, '(', 'DSCs)-derived', supernatant, can]), verbo([enhance]), complemento([proliferation, and, inhibit, apoptosis, of, these, decidual, leukocytes, '(', 'DLCs),', and, promote, 'Th2', cytokines, 'production,', 'IL-4', and, 'IL-10,', with, an, increase, in, 'GATA-3', transcription])]). relacion([sujeto(['They', also]), verbo([inhibit]), complemento([the, secretion, of, 'Th1', 'cytokines,', 'TNF-α', and, 'IFN-γ,', with, a, decrease, in, 'T-bet', transcription, 'It', is, concluded, that, the, secreted, 'CCL2', by, decidual, stromal, cells, increases, 'GATA-3', transcription, and, decreases, 'T-bet', transcription, in, the, decidual, 'leukocytes,', which, contributes, to, 'Th2', polarization, at, 'maternal-fetal', interface])]). relacion([sujeto(['Furthermore,', the, 'Th2', 'cytokines,', 'IL-4', and, 'IL-10,', rather, than, 'Th1', 'cytokines,', was, shown, to]), verbo([increase]), complemento(['CCL2', secretion, of, 'DSC'])]). relacion([sujeto(['Type', 2, innate, lymphoid, cells, '(', 'ILC2s)', produce, cytokines, such, as, 'IL-5', and, 'IL-13,', are]), verbo([required]), complemento([for, immune, defense, against, helminth, 'infections,', and, are, involved, in, the, pathogenesis, of, airway, hyperreactivity])]). relacion([sujeto(['Here,', we]), verbo([have]), complemento([investigated, the, role, of, the, transcription, factor, 'GATA-3', for, 'ILC2', differentiation, and, maintenance])]). relacion([sujeto(['Analysis', of, mice, with, temporary, deletion, of, 'GATA-3', in, all, 'ILCs', showed, that, 'GATA-3', was]), verbo([required]), complemento([for, the, differentiation, and, maintenance, of, 'ILC2s', but, not, for, 'RORγt(+)', 'ILCs'])]). relacion([sujeto(['Thus,', our, data, demonstrate, that, 'GATA-3', is, essential, for, 'ILC2', fate, decisions, and]), verbo([reveal]), complemento([similarities, between, the, transcriptional, programs, controlling, 'ILC', and, 'T', helper, cell, fates])]). relacion([sujeto(['ILC2s']), verbo([mediate]), complemento([parasite, expulsion, but, also, contribute, to, airway, 'inflammation,', emphasizing, the, functional, similarity, between, these, cells, and, 'Th2', cells])]). relacion([sujeto(['Consistent', with, 'this,', we]), verbo([report]), complemento([that, the, transcription, factor, 'GATA3', was, highly, expressed, by, human, 'ILC2s'])]). relacion([sujeto(['CRTH2(+)', 'ILC2s', were, enriched, in, nasal, polyps, of, patients, with, chronic, 'rhinosinusitis,', a, typical, type, 2, -]), verbo([mediated]), complemento([disease])]). relacion([sujeto(['Nasal', polyp, epithelial, cells]), verbo([expressed]), complemento(['TSLP,', which, enhanced, 'STAT5', 'activation,', 'GATA3', 'expression,', and, type, 2, cytokine, production, in, 'ILC2s'])]). relacion([sujeto(['Hence,', we, identify, 'GATA3,', potently]), verbo([regulated]), complemento([by, 'TSLP,', as, an, essential, transcription, factor, for, the, function, of, human, 'ILC2s'])]). relacion([sujeto(['Here,', we, discuss, how, the, natural, 'co-expression', of, these, 'lineage-specifying', transcription, factors]), verbo([has]), complemento([challenged, the, concept, that, the, expression, of, a, single, '\'', master, 'regulator\'', strictly, establishes, an, absolute, 'CD4(+)', 'T', cell, phenotype])]). relacion([sujeto(['This', in, turn]), verbo([has]), complemento([led, to, the, realization, that, 'CD4(+)', 'T', cell, phenotypes, are, more, diverse, than, previously, recognized])]). relacion([sujeto(['To', investigate, the, molecular, mechanism, underlying, 'T-bet']), verbo([mediated]), complemento(['anti-neoplastic', effects, of, cytokine, induced, killer, '(', 'CIK)', cells])]). relacion([sujeto(['Lymphocytes', isolated, from, peripheral, blood, of, leukemic, children, were]), verbo([induced]), complemento([with, 'γ-', interferon, '(', 'IFN-γ),', 'CD3McAb', and, 'interluki-2', '(', 'IL-2),', and, 'co-cultured', with, dendritic, cells, '(', 'DCs)', to, generate, 'DC-CIK', cells])]). relacion([sujeto(['IL-2', and, 'IFN-γ', levels]), verbo([released]), complemento([by, 'DC-CIK', cells, were, quantified, by, 'ELISA'])]). relacion([sujeto(['We', demonstrated, a, time, dependent]), verbo([increase]), complemento([in, 'IL-2', and, 'IFN-γ', levels, after, induction])]). relacion([sujeto(['Treatment', with, mouse, 'anti-human', 'T-bet', monoclonal, antibody, resulted, in, an]), verbo([increase]), complemento([in, the, proportion, of, 'CD4(+)CD25(+)Treg', cells, and, elevation, of, 'Foxp3', and, 'GATA3', mRNA, and, protein, levels])]). relacion([sujeto(['DC-CIK', cells]), verbo([induced]), complemento([with, cytokines, were, strongly, cytotoxic, towards, a, number, of, cancer, cell, lines])]). relacion([sujeto(['Foxp3', and, 'GATA3', were, implicated, in, the, 'T-bet']), verbo([mediated]), complemento(['anti-neoplastic', effects, of, 'DC-CIK', cells, via, activation, of, the, 'Th1', pathway, and, suppression, of, the, 'Th2', and, 'Treg', pathways])]). relacion([sujeto(['The', transcriptional, repressor, 'Bcl6', is, a, critical, arbiter, of, 'Th', cell, 'fate,']), verbo([promoting]), complemento([the, follicular, 'Th', lineage, while, repressing, other, 'Th', cell, lineages])]). relacion([sujeto(['Bcl6(-/-)', 'Tregs', were, competent, at]), verbo([suppressing]), complemento(['T', cell, proliferation, in, vitro, and, 'Th1-type', colitogenic, 'T', cell, responses, in, vivo])]). relacion([sujeto(['In', 'contrast,', 'Bcl6(-/-)', 'Tregs', strongly, exacerbated, lung, inflammation, in, a, model, of, allergic, airway, disease, and]), verbo([promoted]), complemento([higher, 'Th2', 'responses,', including, systemic, upregulation, of, 'microRNA-21'])]). relacion([sujeto(['Bcl6(-/-)', 'Tregs', displayed]), verbo([increased]), complemento([levels, of, the, 'Th2', transcription, factor, 'Gata3', and, other, 'Th2', and, 'Treg', genes])]). relacion([sujeto(['Bcl6', potently, repressed, 'Gata3', transcriptional, 'transactivation,']), verbo([providing]), complemento([a, mechanism, for, the, increased, expression, of, 'Th2', genes, by, 'Bcl6(-/-)', 'Tregs'])]). relacion([sujeto(['Gata3']), verbo([has]), complemento([a, critical, role, in, regulating, 'Foxp3', expression, and, functional, fitness, of, 'Tregs;', 'however,', the, signal, that, regulates, 'Gata3', and, restricts, its, transactivation, of, 'Th2', cytokines, in, 'Tregs', has, remained, unexplored])]). relacion([sujeto(['Our', results, identify, 'Bcl6', as, an, essential, transcription, factor]), verbo([regulating]), complemento(['Gata3', activity, in, 'Tregs'])]). relacion([sujeto(['Thus,', 'Bcl6', represents, a, crucial, regulatory, layer, in, the, 'Treg', functional, program, that, is]), verbo([required]), complemento([for, specific, suppression, of, 'Gata3', and, 'Th2', effector, responses, by, 'Tregs'])]). relacion([sujeto(['HDR', syndrome, '(', 'hypoparathyroidism,', sensorineural, 'deafness,', renal, 'abnormalities)', '(', 'OMIM', #, 146265, ')', is, a, rare, autosomal, dominant, disorder]), verbo([caused]), complemento([by, mutations, in, the, 'GATA-3', gene, '(', 'OMIM', 13120, ')', ',', a, transcription, factor, coding, for, a, protein, involved, in, vertebrate, embryonic, development])]). relacion([sujeto(['More', than, a, hundred, cases, with, variable, renal, features]), verbo([have]), complemento([been, described, so, far])]). relacion([sujeto(['Here,', we]), verbo([report]), complemento([on, a, patient, suffering, from, 'HDR', syndrome, with, glomerular, nephropathy])]). relacion([sujeto(['Hypoparathyroidism', appeared, early, in, childhood, but, the, subsequent, features, of, 'HDR', occurred, later, in, the, form, of, bilateral, sensorineural, deafness, and, renal, insufficiency]), verbo([associated]), complemento([with, nephrocalcinosis])]). relacion([sujeto(['HDR', syndrome, with, glomerular, nephropathy]), verbo([has]), complemento([not, yet, been, reported, to, our, knowledge])]). relacion([sujeto(['Immunosuppressive', 'CD11b(+)Gr1(+)', 'myeloid-derived', suppressor, cells, and, 'TGF-β']), verbo([have]), complemento([been, shown, to, negatively, regulate, host, immunity, against, allografts])]). relacion([sujeto(['T', cells, in, 'alloskin-grafted', 'Smad3-deficient', mice, were, more, likely, to]), verbo([participate]), complemento([in, a, 'Th2-type', immune, 'response,', as, evidenced, by, more, 'Th2-specific', transcription, 'factor,', 'GATA3', 'expression,', and, increased, 'IL-4', and, 'IL-10', 'production,', as, well, as, less, 'Th1-specific', transcription, 'factor,', 'T-bet', 'expression,', and, decreased, 'IL-2', and, 'IFN-γ', production])]). relacion([sujeto(['Increased', 'CXCL1', and, 'CXCL2', as, well, as]), verbo([decreased]), complemento(['CCL3,', 'MCP-1,', and, 'RANTES', chemokines, in, allografts, of, 'Smad3(-/-)', recipients, were, consistently, detected, by, 'real-time', 'PCR'])]). relacion([sujeto(['Further', studies, indicated, that, the]), verbo([increased]), complemento(['CD11b(+)Gr1(+)', myeloid, cells, in, 'Smad3-deficient', mice, were, immunosuppressive, and, responsible, for, the, delayed, allograft, rejection, mainly, via, an, 'NO-dependent', pathway])]). relacion([sujeto(['Thus,', this, study, identifies, 'Smad3', as, an, intrinsic, negative, regulator, that, critically]), verbo([inhibits]), complemento([the, differentiation, and, function, of, immunosuppressive, 'CD11b(+)Gr1(+)', 'myeloid-derived', suppressor, cells])]). relacion([sujeto(['We', determined, that, 'interleukin-12', '(', 'IL-12)', and, 'interferon-γ', '(', 'IFN-γ)', were, redundant, in]), verbo([inducing]), complemento(['T-bet', in, mice, infected, with, 'Toxoplasma', gondii, and, that, 'T-bet', did, not, contribute, to, its, own, expression, when, induced, by, 'IL-12', and, 'IFN-γ'])]). relacion([sujeto(['By', 'contrast,', 'T-bet', and, the, transcription, factor, 'Stat4', were, critical, for, 'IFN-γ', production, whereas, 'IFN-γ', signaling, was, dispensable, for]), verbo([inducing]), complemento(['IFN-γ'])]). relacion([sujeto(['Loss', of, 'T-bet', resulted, in, activation, of, an, endogenous, program, driving, 'Th2', cell, differentiation, in, cells]), verbo([expressing]), complemento(['T-bet-ZsGreen'])]). relacion([sujeto(['Genome-wide', analyses, indicated, that, 'T-bet', directly]), verbo([induced]), complemento([many, 'Th1', 'cell-related', genes, but, indirectly, suppressed, 'Th2', 'cell-related', genes])]). relacion([sujeto(['Our', study, revealed, redundancy, and, synergy, among, several, 'Th1', 'cell-inducing', pathways, in]), verbo([regulating]), complemento([the, expression, of, 'T-bet', and, 'IFN-γ,', and, a, critical, role, of, 'T-bet', in, suppressing, an, endogenous, 'Th2', 'cell-associated', program])]). relacion([sujeto(['We']), verbo([have]), complemento([recently, identified, the, transcription, factor, 'Gata3', as, being, upregulated, in, this, tissue, specifically, at, the, time, of, 'HSC', emergence])]). relacion([sujeto(['In', the, 'post-NOD1', 'group,', serum, 'OVA-specific', 'IgE,', eosinophil, 'counts,', interleukin, '(', 'IL)-13', 'levels,', and, 'GATA-3', mRNA, expression, were, significantly]), verbo([increased]), complemento([and, 'Foxp3(+)', mRNA, expression, and, 'CD4(+)', 'Foxp3(+)', 'T', cells, were, decreased, compared, with, the, 'OVA', group])]). relacion([sujeto(['In', the, 'pre-NOD1', 'group,', 'Foxp3', mRNA, expression, and, 'CD4(+)', 'Foxp3(+)', 'T', cells, were, significantly]), verbo([decreased]), complemento([compared, with, the, 'OVA', group])]). relacion([sujeto(['Although', not, 'significant,', the, 'pre-NOD1', group, showed]), verbo([increases]), complemento([in, serum, 'OVA-specific', 'IgE,', eosinophil, 'counts,', 'IL-13', 'levels,', and, 'GATA-3', mRNA, expression, compared, with, the, 'OVA', group])]). relacion([sujeto(['The', innate, immune, response, through, 'NOD1']), verbo([enhances]), complemento(['allergen-specific', 'Th2', response, and, suppresses, induction, of, regulatory, 'T', cells, in, a, mouse, model, of, allergic, 'rhinitis,', and, the, effects, are, different, depending, on, the, timing, of, exposure, to, 'NOD1', ligand])]). relacion([sujeto(['Previously', we]), verbo([have]), complemento([screened, out, 'Insulin-like', 'Growth', 'Factor', 'Binding', 'Protein', 7, '(', 'IGFBP7)', as, a, differentially, expressed, gene, in, 'post-implantation', uterus, versus, 'pre-implantation', uterus, by, suppressive, subtractive, hybridation])]). relacion([sujeto(['We']), verbo([found]), complemento([that, 'IGFBP7', was, mainly, located, in, the, glandular, epithelium, and, the, 'stroma,', and, was, upregulated, after, embryo, implantation])]). relacion([sujeto([1, -, 'IGFBP7-t']), verbo([expressing]), complemento([partial, 'IGFBP7', was, constructed])]). relacion([sujeto(['Inhibition', of, 'IGFBP7', by, specific, 'DNA', immunization]), verbo([induced]), complemento([significant, reduction, of, implanted, embryos, and, pregnancy, rate])]). relacion([sujeto(['The']), verbo([increase]), complemento([of, 'Tbet', and, the, decrease, of, 'Gata3', were, found, in, mice, peripheral, lymphocytes, by, flow, cytometry])]). relacion([sujeto(['These', results, showed, that, inhibition, of, 'IGFBP7']), verbo([induced]), complemento([pregnancy, failure, by, shifting, uterine, cytokines, to, 'Th1', type, dominance, and, repressing, uterine, decidualization])]). relacion([sujeto(['Our', ability, to, integrate, information, across, platforms]), verbo([provided]), complemento([key, insights, into, previously, defined, gene, expression, subtypes, and, demonstrated, the, existence, of, four, main, breast, cancer, classes, when, combining, data, from, five, 'platforms,', each, of, which, shows, significant, molecular, heterogeneity])]). relacion([sujeto(['The', biological]), verbo([finding]), complemento([of, the, four, main, breast, cancer, subtypes, caused, by, different, subsets, of, genetic, and, epigenetic, abnormalities, raises, the, hypothesis, that, much, of, the, clinically, observable, plasticity, and, heterogeneity, occurs, 'within,', and, not, 'across,', these, major, biological, subtypes, of, breast, cancer])]). relacion([sujeto(['Pure', urothelial, carcinomas, had, an, opposite, pattern, and, were, positive, for, 'S100P', '(', 93, '%', ')', ',', 'GATA3', '(', 93, '%', ')', ',', and, uroplakin, 'III', '(', 67, '%', ')', and, were, negative, for, 'desmoglein-3;', 'CK', 14, was, positive, in, 27, '%', of, 'cases;', 74, '%', of, urothelial, carcinomas, with, squamous, differentiation, had, expression, of, urothelial, and, squamous]), verbo([associated]), complemento([markers, '(', 'S100P,', 83, '%', ;, 'GATA3,', 35, '%', ;, uroplakin, 'III,', 13, '%', ;, 'CK14,', 87, '%', ;, and, 'desmoglein-3,', 70, '%', ')', ',', although, reactivity, for, individual, markers, within, some, tumors, did, not, always, correspond, with, morphologic, differentiation])]). relacion([sujeto(['Our', study, showed, that, a, panel, of, five, antibodies, identifies, squamous, and, urothelial, differentiation, in, most, instances]), verbo([suggesting]), complemento([potential, diagnostic, utility])]). relacion([sujeto(['The', results, indicated, that, topical, administration, of, 'AST', not, only, reduced, the]), verbo([increase]), complemento([of, ear, 'swelling,', spleen, index, and, inflammatory, cells, infiltration, in, 'ACD', 'mice,', but, also, inhibited, remarkably, the, expression, of, 'IFN-gamma,', 'T-bet', and, 'NF-kappaB', p65])]). relacion([sujeto(['It\'s']), verbo([suggested]), complemento([that, 'AST', could, exhibit, suppressive, effects, on, inflammatory, response, and, immune, function, of, 'ACD,', which, indicates, the, possibility, of, developing, 'AST', as, a, novel, immunoregulatory, agent, in, the, treatment, of, 'ACD', and, other, 'immune-related', diseases])]). relacion([sujeto(['Diverse', mechanisms]), verbo([regulate]), complemento([development, of, 'GABAergic', neurons, in, different, regions, of, the, central, nervous, system])]). relacion([sujeto(['We']), verbo([have]), complemento([addressed, the, roles, of, a, proneural, 'gene,', 'Ascl1,', and, a, postmitotic, selector, 'gene,', 'Gata2,', in, the, differentiation, of, 'GABAergic', neuron, subpopulations, in, three, diencephalic, 'prosomeres:', prethalamus, '(', 'P3),', thalamus, '(', 'P2)', and, pretectum, '(', 'P1)'])]). relacion([sujeto(['Although', the, different, proliferative, progenitor, populations, of, 'GABAergic', neurons, commonly]), verbo([express]), complemento(['Ascl1,', they, have, distinct, requirements, for, it, in, promotion, of, 'cell-cycle', exit, and, 'GABAergic', neuron, identity])]). relacion([sujeto(['Subsequently,', 'Gata2', is]), verbo([activated]), complemento([as, postmitotic, 'GABAergic', precursors, are, born])]). relacion([sujeto(['In', 'P1,', 'Gata2']), verbo([regulates]), complemento([the, neurotransmitter, identity, by, promoting, 'GABAergic', and, inhibiting, glutamatergic, neuron, differentiation])]). relacion([sujeto(['Without', 'Gata2,', the, 'GABAergic', precursors, born, in, the, 'pTh-R', fail, to]), verbo([activate]), complemento(['subtype-specific', 'markers,', but, start, to, express, genes, typical, of, 'GABAergic', precursors, in, the, neighbouring, 'P3', domain])]). relacion([sujeto(['Thus,', our, results, demonstrate, diverse, mechanisms]), verbo([regulating]), complemento([differentiation, of, 'GABAergic', neuron, subpopulations, and, suggest, a, role, for, 'Gata2', as, a, selector, gene, of, both, 'GABAergic', neuron, neurotransmitter, and, prosomere, subtype, identities, in, the, developing, diencephalon])]). relacion([sujeto(['The', mechanisms]), verbo([regulating]), complemento([breast, cancer, differentiation, state, are, poorly, understood])]). relacion([sujeto(['Here', we, show, that, the, 'Polycomb', factor, 'EZH2']), verbo([maintains]), complemento([the, differentiation, state, of, 'basal-like', breast, cancer, 'cells,', and, promotes, the, expression, of, progenitor, associated, and, 'basal-lineage', genes])]). relacion([sujeto(['Specifically,', 'EZH2']), verbo([regulates]), complemento([the, composition, of, 'basal-like', breast, cancer, cell, populations, by, promoting, a, '‘bi-lineage’', differentiation, 'state,', in, which, cells, 'co-express', 'basal-', and, 'luminal-lineage', markers])]). relacion([sujeto(['We', show, that, human, 'basal-like', breast, cancers, contain, a, subpopulation, of, 'bi-lineage', 'cells,', and, that, 'EZH2-deficient', cells, give, rise, to, tumors, with, a]), verbo([decreased]), complemento([proportion, of, such, cells])]). relacion([sujeto(['Bi-lineage', cells]), verbo([express]), complemento([genes, that, are, active, in, normal, luminal, 'progenitors,', and, possess, increased, 'colony-formation', 'capacity,', consistent, with, a, primitive, differentiation, state])]). relacion([sujeto(['We']), verbo([found]), complemento([that, 'GATA3,', a, driver, of, luminal, 'differentiation,', performs, a, function, opposite, to, 'EZH2,', acting, to, suppress, 'bi-lineage', identity, and, 'luminal-progenitor', gene, expression])]). relacion([sujeto(['GATA3', levels]), verbo([increase]), complemento([upon, 'EZH2', 'silencing,', mediating, a, decrease, in, 'bi-lineage', cell, numbers])]). relacion([sujeto(['Our', findings]), verbo([reveal]), complemento([a, novel, role, for, 'EZH2', in, controlling, 'basal-like', breast, cancer, differentiation, state, and, 'intra-tumoral', cell, composition])]). relacion([sujeto(['Transcription', factors, '(', 'TFs)', can]), verbo([regulate]), complemento([different, sets, of, genes, to, determine, specific, cell, types, by, means, of, combinatorial, codes])]). relacion([sujeto(['We', previously, identified, 'closely-spaced', 'TF']), verbo([binding]), complemento([motifs, located, 8.2, -, 8.5, kb, 5, '\'', to, the, 'ATG', of, the, murine, 'Pou4f3', 'gene,', a, gene, required, for, late, hair, cell, '(', 'HC)', differentiation, and, survival])]). relacion([sujeto(['These', 'motifs,', 100, '%']), verbo([conserved]), complemento([among, four, mammalian, 'species,', include, a, cluster, of, 'E-boxes', preferred, by, 'TCF3/ATOH1', heterodimers, as, well, as, motifs, for, 'GATA', factors, and, 'SP1'])]). relacion([sujeto(['We', hypothesized, that, these, factors, might]), verbo([interact]), complemento([to, regulate, the, 'Pou4f3', gene, and, possibly, induce, a, 'HC', phenotype, in, 'non-sensory', cells, of, the, cochlea])]). relacion([sujeto([hATOH1, or, hTCF3, alone]), verbo([induced]), complemento(['Pou4f3/GFP', cells, but, hGATA3, and, hSP1, did, not])]). relacion([sujeto([hATOH1, but, not, hTCF3]), verbo([induced]), complemento([conversion, of, greater, epithelial, ridge, cells, into, 'Pou4f3/GFP', and, myosin, 'VIIa', 'double-positive', cells])]). relacion([sujeto(['Transfection', of, hATOH1, in, combination, with, hTCF3, or, hGATA3]), verbo([induced]), complemento([2, -, 3, 'X', more, 'Pou4f3/GFP', 'cells,', and, similarly, enhanced, 'Pou4f3/GFP', and, myosin, 'VIIa', 'double-positive', 'cells,', when, compared, to, hATOH1, alone])]). relacion([sujeto(['Immunohistochemical', analysis, '(', 'IHC)', for, 'GATA']), verbo([binding]), complemento([protein, 3, '(', 'GATA3),', thrombomodulin, '(', 'THROMBO),', and, uroplakin, 'III', was, performed, on, a, tissue, microarray, '(', 'TMA)', containing, 35, cases, of, invasive, 'high-grade', 'UC'])]). relacion([sujeto(['Of', the, 7, cases, that, failed, to]), verbo([express]), complemento(['GATA3,', 5, were, positive, for, 'THROMBO', 'and/or', uroplakin, 'III,', whereas, 2, were, negative, for, all, 3, markers])]). relacion([sujeto(['This', study, investigated, whether, resveratrol]), verbo([inhibited]), complemento([the, development, of, food, allergy, by, using, a, mouse, model, of, the, disease])]). relacion([sujeto(['We']), verbo([found]), complemento([that, mice, fed, resveratrol, showed, reduced, 'OVA-specific', serum, 'IgE', 'production,', anaphylactic, 'reaction,', and, 'OVA-induced', 'IL-13', and, 'IFN-ã', production, from, the, mesenteric, lymph, nodes, '(', 'MLNs)', and, spleens, in, comparison, to, the, control, 'mice,', following, oral, sensitization, with, 'OVA', plus, 'CT'])]). relacion([sujeto(['In', 'addition,', resveratrol]), verbo([inhibited]), complemento(['OVA', plus, 'CT-induced', 'IL-4,', 'IL-13,', and, 'IFN-ã', production, in, splenocytes, from, 'DO11'])]). relacion([sujeto([10, mice]), verbo([associated]), complemento([with, inhibition, of, 'GATA-3', and, 'T-bet', expression])]). relacion([sujeto(['Furthermore,', resveratrol]), verbo([suppressed]), complemento([the, 'OVA', plus, 'CT-induced', 'CD25', expression, and, 'IL-2', production, in, 'DO11'])]). relacion([sujeto([10, 'mice-splenocytes', in, association, with]), verbo([decreases]), complemento([in, 'CD80', and, 'CD86', expression, levels])]). relacion([sujeto(['Finally,', resveratrol]), verbo([suppressed]), complemento(['CT-induced', cAMP, elevation, in, association, with, decreases, in, 'CD80', and, 'CD86', expression, levels, in, 'BMDCs'])]). relacion([sujeto(['Ingestion', of, resveratrol]), verbo([prevented]), complemento([the, development, of, a, food, allergy, model, in, mice])]). relacion([sujeto(['Given', the, in, vitro, 'findings,', resveratrol, might, do, so, by]), verbo([inhibiting]), complemento(['DC', maturation, and, subsequent, early, 'T', cell, activation, and, differentiation, via, downregulation, of, 'CT-induced', cAMP, activation, in, mice])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, resveratrol, may, have, potential, for, prophylaxis, against, food, allergy])]). relacion([sujeto(['Immune', tolerance, is, instituted, early, in, 'life,', during, which, time, regulatory, 'T', '(', 'T(reg))', cells]), verbo([have]), complemento([an, important, role])]). relacion([sujeto(['Recurrent', infections, with, respiratory, syncytial, virus, '(', 'RSV)', in, early, life]), verbo([increase]), complemento([the, risk, for, asthma, in, adult, life])]). relacion([sujeto(['Repeated', infection, of, infant, mice, tolerized, to, ovalbumin, '(', 'OVA)', through, their, 'mother\'s', milk, with, 'RSV']), verbo([induced]), complemento([allergic, airway, disease, in, response, to, 'OVA', sensitization, and, 'challenge,', including, airway, 'inflammation,', 'hyper-reactivity', and, higher, 'OVA-specific', 'IgE,', as, compared, to, uninfected, tolerized, control, mice])]). relacion([sujeto(['Virus', infection]), verbo([induced]), complemento(['GATA-3', expression, and, 'T', helper, type, 2, '(', 'T(H)2)', cytokine, production, in, forkhead, box, 'P3', '(', 'FOXP3)(+)', 'T(reg)', cells, and, compromised, the, suppressive, function, of, pulmonary, 'T(reg)', cells, in, a, manner, that, was, dependent, on, 'interleukin-4', receptor, α, '(', 'IL-4Rα)', expression, in, the, host])]). relacion([sujeto(['Thus,', by]), verbo([promoting]), complemento([a, 'T(H)2-type', inflammatory, response, in, the, 'lung,', 'RSV', induced, a, 'T(H)2-like', effector, phenotype, in, 'T(reg)', cells, and, attenuated, tolerance, to, an, unrelated, antigen, '(', 'allergen)'])]). relacion([sujeto(['Our', findings, highlight, a, mechanism, by, which, viral, infection]), verbo([targets]), complemento([a, 'host-protective', mechanism, in, early, life, and, increases, susceptibility, to, allergic, disease])]). relacion([sujeto(['Conventional', dendritic, cells, '(', 'cDCs)']), verbo([have]), complemento([been, reported, to, participate, in, the, pathophysiology, of, acute, lung, injury, '(', 'ALI)'])]). relacion([sujeto(['FLT3L', pretreatment, further]), verbo([stimulated]), complemento([the, accumulation, and, maturation, of, pulmonary, 'cDCs,', leading, to, a, markedly, increased, 'LWW/BW', and, aggravated, lung, histopathology])]). relacion([sujeto(['In', 'contrast,', lestaurtinib, pretreatment]), verbo([inhibited]), complemento([the, accumulation, and, maturation, of, pulmonary, 'cDCs,', leading, to, a, significantly, decreased, 'LWW/BW', and, improved, lung, histopathology])]). relacion([sujeto(['Lestaurtinib', administration, also]), verbo([suppressed]), complemento([lung, 'MPO', 'activity,', 'T-bet/GATA-3', mRNA, ratio, and, production, of, 'IL-6', and, 'IFN-γ'])]). relacion([sujeto(['Our', findings, show, that, 'FLT3', signaling, ameliorates, 'ALI', by]), verbo([regulating]), complemento([the, accumulation, and, maturation, of, pulmonary, 'cDCs,', suggesting, an, innovative, pharmacotherapy, for, 'ALI'])]). relacion([sujeto(['To', identify, which, genes, are]), verbo([associated]), complemento([with, the, changes, of, malignancy, of, 'teratocarcinomas,', we, established, a, tumorigenesis, model, in, which, teratocarcinoma, were, induced, via, injecting, embryonic, stem, cells, into, 'immuno-deficiency', 'mice,', isolating, teratocarcinoma, stem, cell, from, a, teratocarcinoma, in, 'serum-free', culture, medium, and, injecting, teratocarcinoma, stem, cells, into, 'immune-deficient', mice, continuously])]). relacion([sujeto(['By', using, 'high-throughput', deep, sequence, 'technology,', we, identified, 26, differentially]), verbo([expressed]), complemento([genes, related, to, the, changes, of, characteristics, of, teratocarcinoma, stem, cell, in, which, 18, out, of, 26, genes, were, 'down-regulated', and, 8, genes, were, 'up-regulated'])]). relacion([sujeto(['Among', these, 'genes,', several, 'tumor-related', genes, such, as, 'Gata3,', 'Arnt', and, 'Tdgf1,', epigenetic]), verbo([associated]), complemento([genes, such, as, 'PHC1', and, 'Uty', were, identified])]). relacion([sujeto(['Pathway', enrichment, analysis, result, revealed, that, 'Wnt', signaling, 'pathway,', primary, immunodeficiency, 'pathway,', antigen, processing, and, presentation, pathway, and, allograft, rejection, pathway, were]), verbo([involved]), complemento([in, the, teratocarcinoma, tumorigenesis, '(', corrected, p, 'value<0'])]). relacion([sujeto(['Highly']), verbo([regulated]), complemento([expression, of, the, negative, costimulatory, molecule, cytotoxic, 'T-lymphocyte', 'antigen-4', '(', 'CTLA-4)', on, 'T', cells, modulates, 'T-cell', activation, and, proliferation])]). relacion([sujeto(['CTLA-4', is, preferentially]), verbo([expressed]), complemento([in, 'Th2', 'T', 'cells,', whose, differentiation, depends, on, the, transcriptional, regulator, 'GATA3'])]). relacion([sujeto(['GATA3', is]), verbo([regulated]), complemento([by, phosphorylation, and, ubiquitination])]). relacion([sujeto(['In', 'SS', 'cells,', we, detected]), verbo([increased]), complemento([polyubiquitinated, proteins, and, activated, 'GATA3'])]). relacion([sujeto(['We', hypothesized, that, proteasome, dysfunction, in, 'SS', 'T', cells, may]), verbo([lead]), complemento([to, 'GATA3', and, 'CTLA-4', overexpression])]). relacion([sujeto(['The']), verbo([increased]), complemento(['CTLA-4', was, functionally, inhibitory, in, a, mixed, lymphocyte, reaction, '(', 'MLR)'])]). relacion([sujeto(['GATA3', directly, transactivated, the, 'CTLA-4', 'promoter,', and, knockdown, of, 'GATA3', messenger, 'RNA', and, protein]), verbo([inhibited]), complemento(['CTLA-4', induction, mediated, by, bortezomib])]). relacion([sujeto(['Finally,', knockdown, of, 'GATA3', in, 'patient\'s', malignant, 'T', cells]), verbo([suppressed]), complemento(['CTLA-4', expression])]). relacion([sujeto(['Here', we, demonstrate, a, new, 'T-cell', regulatory, pathway, that, directly, links]), verbo([decreased]), complemento([proteasome, degradation, of, 'GATA3,', 'CTLA-4', 'upregulation,', and, inhibition, of, 'T-cell', responses])]). relacion([sujeto(['One', mechanism, by, which, 'TCF7L2', could, influence, expression, of, genes]), verbo([involved]), complemento([in, diverse, diseases, is, by, binding, to, distinct, regulatory, regions, in, different, tissues])]). relacion([sujeto(['We', identified, 116, ',', 0, 'non-redundant', 'TCF7L2']), verbo([binding]), complemento(['sites,', with, only, 1, ',', 864, sites, common, to, the, six, cell, lines])]). relacion([sujeto(['Using', 'ChIP-seq,', we, showed, that, many, genomic, regions, that, are, marked, by, both, 'H3K4me1', and, 'H3K27Ac', are, also]), verbo([bound]), complemento([by, 'TCF7L2,', suggesting, that, 'TCF7L2', plays, a, critical, role, in, enhancer, activity])]). relacion([sujeto(['Bioinformatic', analysis, of, the, cell, 'type-specific', 'TCF7L2']), verbo([binding]), complemento([sites, revealed, enrichment, for, multiple, transcription, 'factors,', including, 'HNF4alpha', and, 'FOXA2', motifs, in, 'HepG2', cells, and, the, 'GATA3', motif, in, 'MCF7', cells])]). relacion([sujeto(['Interestingly,', in, 'MCF7', cells, the, 'TCF7L2', motif, is, enriched, in, most, 'TCF7L2', sites, but, is, not, enriched, in, the, sites]), verbo([bound]), complemento([by, both, 'GATA3', and, 'TCF7L2'])]). relacion([sujeto(['This', analysis]), verbo([suggested]), complemento([that, 'GATA3', might, tether, 'TCF7L2', to, the, genome, at, these, sites])]). relacion([sujeto(['To', test, this, 'hypothesis,', we, depleted, 'GATA3', in, 'MCF7', cells, and, showed, that, 'TCF7L2']), verbo([binding]), complemento([was, lost, at, a, subset, of, sites])]). relacion([sujeto(['RNA-seq', analysis]), verbo([suggested]), complemento([that, 'TCF7L2', represses, transcription, when, tethered, to, the, genome, via, 'GATA3'])]). relacion([sujeto(['Our', studies, demonstrate, a, novel, relationship, between, 'GATA3', and, 'TCF7L2,', and]), verbo([reveal]), complemento([important, insights, into, 'TCF7L2-mediated', gene, regulation])]). relacion([sujeto(['Fermentation']), verbo([has]), complemento([a, tremendous, capacity, to, transform, chemical, structures])]). relacion([sujeto(['The', antiinflammatory, effects, of, fish, oil]), verbo([have]), complemento([been, described, in, many, 'diseases,', but, the, beneficial, effects, by, which, fermented, olive, flounder, oil, '(', 'FOF)', modulates, the, allergic, response, is, poorly, understood])]). relacion([sujeto(['In', this, 'study,', we, produced, 'FOF', and, tested, its, ability, to]), verbo([suppress]), complemento([the, various, allergic, inflammatory, responses])]). relacion([sujeto(['The', ability, of, 'FOF', to]), verbo([modulate]), complemento([the, immune, system, was, investigated, using, a, mouse, model, of, 'AD'])]). relacion([sujeto(['The', 'FOF-treated', group, showed, significantly]), verbo([decreased]), complemento([immunoglobulin, 'E', '(', 'IgE)', and, histamine, in, serum])]). relacion([sujeto(['Also,', the]), verbo([increased]), complemento(['TSLP', expression, was, significantly, inhibited, in, the, 'FOF', 'group;', the, 'FOF-treated', group, was, not, appreciably, different, from, the, hydrocort, cream, treatment, group])]). relacion([sujeto(['Splenocytes', from, mice, treated, with, 'FOF', produced, significantly, less, 'IFN-γ,', 'IL-4,', 'T-box', transcription, factor, '(', 'T-bet)', and, 'GATA']), verbo([binding]), complemento([protein, 3, '(', 'GATA3)', expression, compared, with, the, induction, group])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, 'FOF', may, be, effective, in, treating, the, allergic, symptoms, of, 'AD'])]). relacion([sujeto(['Since', processes, in, 'well-known', model, organisms]), verbo([have]), complemento([specific, features, different, from, those, in, 'Bos', 'taurus,', the, organism, under, 'study,', a, good, way, to, describe, gene, regulation, in, ruminant, embryos, would, be, a, 'species-specific', consideration, of, closely, related, species, to, 'cattle,', sheep, and, pig])]). relacion([sujeto(['Besides', these, closely, related, and, biologically, relevant, 'species,', there, is, indeed, much, more, knowledge, of, '(', 'i)', trophoblast, proliferation, and, differentiation, or, '(', 'ii)', embryogenesis, in, human, and, mouse, 'species,', which]), verbo([provides]), complemento([opportunities, for, reconstructing, proliferation, 'and/or', differentiation, processes, in, other, mammalian, 'embryos,', including, ruminants])]). relacion([sujeto(['To', evaluate, the, quality, of, this, &, 'quot;mining",', we, took, advantage, of, studies, that]), verbo([reported]), complemento([gene, expression, profiles, during, the, elongation, of, bovine, embryos, and, defined, a, list, of, transcription, factors, '(', or, 'TF,', n, =, 64, ')', that, we, used, as, biological, &, 'quot;gold', 'standard"'])]). relacion([sujeto(['To']), verbo([gain]), complemento([knowledge, on, 'molecular-genetic', regulations, in, a, non, model, 'organism,', we, offer, an, approach, based, on, 'literature-mining', and, score, arrangement, of, data, from, model, organisms])]). relacion([sujeto(['They']), verbo([require]), complemento([data, input, coming, from, all, various, databases, for, any, kind, of, biological, issue, once, the, data, has, been, prepared, according, to, keywords, for, the, studied, topic, and, 'species;', we, can, provide, data, sample, to, illustrate, the, use, and, functionality, of, the, workflow])]). relacion([sujeto(['They', thus, stand, so, far, for, putative, 'TF']), verbo([acting]), complemento([during, bovine, embryo, 'elongation,', but, might, be, retrieved, from, a, recent, 'RNA', sequencing, dataset, '(', 'Mamo', et, al])]). relacion([sujeto(['Beyond', the, 246, 'TF', that, appeared]), verbo([expressed]), complemento([in, bovine, elongating, 'tissues,', we, restricted, our, interpretation, to, those, occurring, within, a, list, of, 50, 'top-ranked', genes])]). relacion([sujeto(['A', workflow]), verbo([providing]), complemento([search, for, transcription, factors, acting, in, bovine, elongation, was, developed])]). relacion([sujeto(['The', model, assumed, that, proteins, sharing, the, same, protein, domains, in, closely, related, species, had, the, same, protein, 'functionalities,', even, if, they, were, differently]), verbo([regulated]), complemento([among, species, or, involved, in, somewhat, different, pathways])]). relacion([sujeto(['Absence', of, phagocyte, 'NADPH', oxidase, '(', 'NOX2)', activity]), verbo([causes]), complemento([chronic, granulomatous, disease, '(', 'CGD),', a, primary, immunodeficiency, characterized, by, recurrent, bacterial, infections])]). relacion([sujeto(['In', contrast, to, this, innate, immune, 'deficit,', 'CGD', patients, and, animal, models, display, a, predisposition, toward, autoimmune, disease, and]), verbo([enhanced]), complemento([response, to, 'Helicobacter', pylori, and, influenza, virus, infection])]). relacion([sujeto(['Activation', of, purified, naive, 'CD4(+)', 'T', cells, from, 'NOX2-deficient', mice]), verbo([led]), complemento([to, augmented, 'IFN-γ', and, diminished, 'IL-4', production, and, an, increased, ratio, of, expression, of, the, 'T(H)1-specific', transcription, factor, 'T-bet', versus, the, 'T(H)2-specfic', transcription, factor, 'GATA-3,', consistent, with, a, 'T(H)1', skewing, of, naïve, 'T', cells])]). relacion([sujeto(['These', data]), verbo([suggest]), complemento([that, 'TCR-induced', 'ROS', generation, from, 'NOX2', activation, can, regulate, the, adaptive, immune, response, in, a, 'T-cell-inherent', 'fashion,', and, propose, a, possible, role, for, redox, signaling, in, 'T', helper, differentiation])]). relacion([sujeto(['To']), verbo([gain]), complemento([insights, into, the, molecular, mechanisms, of, 'Foxp3-mediated', gene, 'expression,', we, purified, 'Foxp3', complexes, and, explored, their, composition])]). relacion([sujeto(['Biochemical', and, 'mass-spectrometric', analyses, revealed, that, 'Foxp3', forms, multiprotein, complexes, of, 400, -, 800, kDa, or, larger, and, identified, 361]), verbo([associated]), complemento(['proteins,', '∼30%', of, which, were, transcription, related])]). relacion([sujeto(['Foxp3', directly]), verbo([regulated]), complemento([expression, of, a, large, proportion, of, the, genes, encoding, its, cofactors])]). relacion([sujeto(['Functional', analysis, of, the, cooperation, of, 'Foxp3', with, one, such, 'partner,', 'GATA-3,']), verbo([provided]), complemento([additional, evidence, for, a, network, of, transcriptional, regulation, afforded, by, 'Foxp3', and, its, associates, to, control, distinct, aspects, of, 'T(reg)', cell, biology])]). relacion([sujeto(['The', identifying, of]), verbo([binding]), complemento([sites, for, transcription, factors, is, a, key, component, of, gene, regulatory, network, analysis])]). relacion([sujeto(['Because', of, the, importance, of, in, silico, mapping, of, tentative]), verbo([binding]), complemento(['sites,', we, previously, developed, an, approach, for, 'PWM', optimization, that, substantially, improves, the, accuracy, of, such, mapping])]). relacion([sujeto(['The', refined, 'PWM', also, facilitates, in, silico, identification, of, novel]), verbo([binding]), complemento([sites, that, are, supported, by, experimental, data])]). relacion([sujeto(['We', also, describe, uncommon, positioning, of]), verbo([binding]), complemento([motifs, for, several, 'T-cell', lineage, specific, factors, in, human, promoters])]). relacion([sujeto(['Therefore', our, new, 'di-nucleotide', 'PWM']), verbo([provides]), complemento([new, insight, into, plausible, transcriptional, regulatory, interactions, in, human, promoters])]). relacion([sujeto(['T-bet', and, 'GATA-3', are, transcriptional, factors]), verbo([involved]), complemento([in, 'Th1', and, 'Th2', cell, 'differentiation,', although, their, concomitant, roles, at, protein, levels, in, target, organs, during, human, allergic, disease, have, not, been, assessed])]). relacion([sujeto(['There', were]), verbo([increases]), complemento([in, 'CD3(+)STAT6(+)cells', '(', 'P = 0'])]). relacion([sujeto(['Following', 'PPD', challenge, 'CD3(+)STAT4(+)cells', and, 'CD3(+)T-bet(+)cells']), verbo([increased]), complemento([in, both, groups, compared, with, diluent, '(', 'P = 0'])]). relacion([sujeto(['Dysregulation', of, 'Th1', transcription, may, contribute, to, heightened, expression, of, 'STAT6', and, 'GATA3']), verbo([leading]), complemento([to, exaggerated, 'Th2-driven', manifestations, of, allergic, disease])]). relacion([sujeto(['To', elucidate, whether, epigenetic, mechanisms, are, responsible, for, the]), verbo([loss]), complemento([of, the, 'T-cell', 'phenotype,', we, treated, anaplastic, large, cell, lymphoma, and, 'T-cell', 'lymphoma/leukemia', cell, lines, '(', 'n=4,', 'each)', with, epigenetic, modifiers, to, evoke, 'DNA', demethylation, and, histone, acetylation])]). relacion([sujeto(['Global', gene, expression, data, from, treated, and, untreated, cell, lines, were, generated, and, 'selected,', and, differentially]), verbo([expressed]), complemento([genes, were, evaluated, by, 'real-time', reverse, transcriptase, polymerase, chain, reaction, and, western, blot, analysis])]). relacion([sujeto(['Instead,', the, same, treatment]), verbo([induced]), complemento([in, 'T', 'cells:', '(', 'i)', an, 'up-regulation', of, anaplastic, large, cell, 'lymphoma-characteristic', genes, '(', e])]). relacion([sujeto(['Our', data]), verbo([suggest]), complemento([that, epigenetically, activated, suppressors, '(', e])]). relacion([sujeto(['ID2)', contribute, to, the, 'down-regulation', of, the, 'T-cell', expression, program, in, anaplastic, large, cell, 'lymphoma,', which, is]), verbo([maintained]), complemento([by, trimethylation, of, histone, 'H3', lysine, 27])]). relacion([sujeto(['The', oncogenic, transcription, factor, 'TAL1/SCL', is, aberrantly]), verbo([expressed]), complemento([in, over, 40, '%', of, cases, of, human, 'T cell', acute, lymphoblastic, leukemia, '(', 'T-ALL),', emphasizing, its, importance, in, the, molecular, pathogenesis, of, 'T-ALL'])]). relacion([sujeto(['We', show, that, 'TAL1', forms, a, positive, interconnected, autoregulatory, loop, with, 'GATA3', and, 'RUNX1', and, that, the, 'TAL1', complex, directly]), verbo([activates]), complemento([the, 'MYB', 'oncogene,', forming, a, positive, 'feed-forward', regulatory, loop, that, reinforces, and, stabilizes, the, 'TAL1-regulated', oncogenic, program])]). relacion([sujeto(['One', of, the, critical, downstream]), verbo([targets]), complemento([in, this, circuitry, is, the, 'TRIB2', 'gene,', which, is, oppositely, regulated, by, 'TAL1', and, 'E2A/HEB', and, is, essential, for, the, survival, of, 'T-ALL', cells])]). relacion([sujeto(['The', present, study, evaluated, the, expression, profile, of, 19, genes, previously]), verbo([reported]), complemento([in, microarray, studies, and, associated, with, resistance, or, sensitivity, to, vincristine, '(', 'RPLP2,', 'CD44,', 'TCFL5,', 'KCNN1,', 'TRIM24),', prednisolone, '(', 'F8A,', 'CDK2AP1,', 'BLVRB,', 'CD69),', daunorubicin, '(', 'MAP3K12,', 'SHOC2,', 'PCDH9,', 'EGR1,', 'KCNN4)', and, 'l-asparaginase', '(', 'GPR56,', 'MAN1A1,', 'CLEC11A,', 'IGFBP7,', 'GATA3)'])]). relacion([sujeto(['The', 'up-regulation', of, 'SHOC2', was, also]), verbo([associated]), complemento([with, better, 5, -, year, 'event-free', survival, '(', 'EFS)', in, univariate, and, multivariate, analysis, '(', p, =, 0.02, and, p, =, 0.03, ',', 'respectively)'])]). relacion([sujeto(['These', findings, highlight, genes, that, could, be]), verbo([associated]), complemento([with, clinical, and, biological, prognostic, factors, in, childhood, 'ALL,', suggesting, that, these, genes, may, characterize, and, play, a, role, in, the, treatment, outcome, of, some, 'ALL', subsets])]). relacion([sujeto(['To', investigate, the, expression, pattern, of, histone, deacetylase, 9, '(', 'HDAC9)', in, peripheral, blood, of, asthmatics, and, its, effect, on, immune, cells, '(', 'Th2,', 'Th17,', 'Tregs)']), verbo([involved]), complemento([in, the, pathogenesis, of, asthma])]). relacion([sujeto(['Forty-seven', asthmatics, from, 'Ruijin', 'Hospital', were]), verbo([recruited]), complemento([and, assigned, to, 'intermittent,', mild, and, 'moderate-severe', groups])]). relacion([sujeto(['The', 'HDAC9', mRNA, expression, levels, of, 'intermittent,', mild, and, 'moderate-severe', groups, were, 3.2, ±, 0.5, ',', 89.6, ±, 18.0, ',', 323.0, ±, 65.3, ',', 'respectively,', which, were]), verbo([associated]), complemento([with, the, severity, of, disease, '(', 'H', =, 11.32, ',', 'P', &, 'lt;', 0.05, ')'])]). relacion([sujeto(['The', level, of, 'TGF-β', was]), verbo([decreased]), complemento([in, the, asthmatic, groups, as, compared, to, the, healthy, 'control,', but, the, difference, did, not, reach, significance])]). relacion([sujeto(['HDAC9', mRNA, expression, was, 'up-regulated', in, peripheral, blood, of, 'asthmatics,', which, was, not, only]), verbo([associate]), complemento([with, the, 'Th2', master, transcriptional, factors, 'GATA3,', cytokine, 'IL-4', 'mRNA,', 'Th17', and, 'Treg', 'cell-related', 'cytokines,', but, also, with, 'FEV(1)%', in, 'moderate-severe', asthma])]). relacion([sujeto(['Blockage', of, nerve, growth, factor, '(', 'NGF)', by, 'anti-NGF', antibodies, can]), verbo([inhibit]), complemento([allergic, airway, 'hyper-responsiveness', in, mice])]). relacion([sujeto(['OVA', challenge]), verbo([induced]), complemento([severe, airway, 'resistance,', 'inflammation,', higher, levels, of, 'IL-4,', 'TNFα,', 'IL-17A,', 'TGFβ,', 'GATA-3', and, 'RORγT', expression, and, increased, 'Th2', and, 'Th17', cells, and, 'IgE', 'responses,', but, decreased, 'IFNγ', and, 'IL-10', 'responses,', 'T-bet', and, 'Foxp3', expression, and, 'Th1', and, 'Tregs'])]). relacion([sujeto(['Treatment', with, 'anti-NGF', significantly, reduced, allergic, airway, resistance, and, 'inflammation,', 'up-regulated', 'IFNγ,', 'IL-10,', 'TGFβ,', 'T-bet,', and, 'Foxp3', 'expression,']), verbo([increased]), complemento(['Th1', and, 'Tregs,', but, 'down-regulated', 'IL-4,', 'TNFα,', 'IL-17A,', 'RORγT', and, 'GATA-3', expression, and, reduced, 'Th2', and, 'Th17', 'cells,', accompanied, by, increased, serum, 'IgG2a'])]). relacion([sujeto(['Anti-NGF']), verbo([inhibits]), complemento([allergic, airway, inflammation, by, modulating, the, balance, of, 'pro-', and, 'anti-asthmatic', 'T', cell, responses, in, the, lungs, of, mice])]). relacion([sujeto(['Recently', another, 'ILC', subset]), verbo([has]), complemento([been, 'identified,', which, is, dependent, on, 'RORα', for, its, development, and, is, dedicated, to, the, production, of, the, 'Th2', cytokines, 'IL-5', and, 'IL-13'])]). relacion([sujeto(['These', 'ILCs']), verbo([have]), complemento([been, termed, type, 2, 'ILCs'])]). relacion([sujeto(['Here', we, review, the, current, knowledge, with, regard, to, the, transcription, factors]), verbo([involved]), complemento([in, the, development, and, functions, of, 'ILCs'])]). relacion([sujeto(['IL-6']), verbo([regulates]), complemento([the, proliferation, and, differentiation, of, 'T', 'cells,', and, elicits, immunoglobulin, production, in, 'B', cells])]). relacion([sujeto(['The', protein, comprises, the, signal, 'peptide,', the, 'IL-6', family, 'signature,', and]), verbo([conserved]), complemento([amino, acid, residues, found, in, 'IL-6', sequences, of, other, teleost])]). relacion([sujeto(['Additionally,', higher, levels, of, igm, mRNA, and]), verbo([translated]), complemento([protein, were, detected, in, 'rgIL-6', stimulated, fish])]). relacion([sujeto(['These', results, indicate, that, 'IL-6', in, groupers]), verbo([regulates]), complemento([the, differentiation, of, naїve, 'T', helper, cells, into, 'Th2', cells, and, elicits, the, production, of, antibodies])]). relacion([sujeto(['Ectopic', expression, of, 'ZBTB32']), verbo([suppressed]), complemento(['CIITA', and, 'I-A', gene, expression, in, 'B', cells])]). relacion([sujeto(['ZBTB32', was]), verbo([found]), complemento([to, bind, to, the, 'CIITA', 'gene,', suggesting, that, 'ZBTB32', directly, regulates, 'CIITA'])]). relacion([sujeto(['Lastly,', 'ZBTB32', and, 'Blimp-1', 'coimmunoprecipitated,']), verbo([suggesting]), complemento([that, the, two, repressors, may, ultimately, function, together, to, silence, 'CIITA', expression])]). relacion([sujeto(['NKX3-1', is, a, prostate, specific, homeobox, gene]), verbo([activated]), complemento([in, 'T-ALL', patients, expressing, oncogenic, 'TAL1', or, displaying, immature, 'T-cell', characteristics])]). relacion([sujeto(['After', investigating, regulation, of, 'NKX3-1', in, primary, cells, and, cell, 'lines,', we]), verbo([report]), complemento([its, ectopic, expression, in, 'T-ALL', cells, independent, of, chromosomal, rearrangements])]). relacion([sujeto(['Moreover,', we, showed, that, 'NKX3-1', is, directly]), verbo([activated]), complemento([by, early, 'T-cell', homeodomain, factor, 'MSX2'])]). relacion([sujeto(['These', activators, were]), verbo([regulated]), complemento([by, 'MLL', 'and/or', by, 'IL7-,', 'BMP4-', and, 'IGF2-signalling'])]). relacion([sujeto(['Finally,', we, demonstrated, homeobox, gene, 'SIX6', as, a, direct, leukemic]), verbo([target]), complemento([of, 'NKX3-1', in, 'T-ALL'])]). relacion([sujeto(['Evidence']), verbo([suggests]), complemento([that, nebulized, lidocaine, is, beneficial, in, asthma, 'therapy,', but, to, what, extent, and, the, mechanisms, underlying, this, effect, remain, poorly, understood])]). relacion([sujeto(['Inhaled', lidocaine]), verbo([inhibited]), complemento(['ovalbumin-induced', airway, hyperreactivity, to, 'methacholine,', and, accumulation, of, 'lymphocytes,', 'neutrophils,', and, eosinophils, in, bronchoalveolar, lavage, fluid, 24, h, after, the, last, allergen, provocation])]). relacion([sujeto(['Lidocaine', administration, also]), verbo([prevented]), complemento([other, pathophysiological, changes, triggered, by, ovalbumin, in, lung, 'tissue,', including, peribronchial, eosinophil, and, neutrophil, 'infiltration,', subepithelial, 'fibrosis,', increased, content, of, collagen, and, 'mucus,', matrix, 'metalloproteinase-9', 'activity,', and, increased, levels, of, 'IL-4,', 'IL-5,', 'IL-13,', and, 'eotaxin-1'])]). relacion([sujeto(['Furthermore,', inhaled, lidocaine]), verbo([inhibited]), complemento([lung, tissue, 'GATA-3', expression, in, 'ovalbumin-challenged', mice])]). relacion([sujeto(['We', also, demonstrated, that, lidocaine]), verbo([inhibited]), complemento([the, expression, of, 'GATA-3', in, 'ovalbumin-stimulated', 'T', cells, in, vitro])]). relacion([sujeto(['Inhaled', lidocaine]), verbo([prevents]), complemento([eosinophilic, 'inflammation,', overproduction, of, 'mucus,', and, peribronchial, fibrosis, in, a, murine, model, of, 'asthma,', and, impaired, airway, 'hyperreactivity,', possibly, by, inhibiting, 'allergen-evoked', 'GATA-3', expression, and, the, subsequent, 'up-regulation', of, proinflammatory, cytokines, and, chemokines])]). relacion([sujeto(['In', the, presence, of, 'IL-15,', tanshinones]), verbo([increased]), complemento(['NK', cell, 'maturation,', 'NK', cell, differentiation, and, the, expression, of, several, transcription, 'factors,', including, 'Id2,', 'GATA3,', 'T-bet,', and, 'Ets-1'])]). relacion([sujeto(['Additionally,', tanshinones]), verbo([increased]), complemento([p38, 'MAPK', phosphorylation, during, 'NK', cell, differentiation])]). relacion([sujeto(['Furthermore,', the, p38, inhibitor, 'SB203580', blocked, the, developmental, effects, of, the, tanshinones, and]), verbo([suppressed]), complemento(['Id2,', 'T-bet,', and, 'Ets-1', expression, during, 'NK', cell, differentiation])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, tanshinones, significantly, increased, 'IL-15-induced', 'NK', cell, differentiation, via, enhancing, the, p38, phosphorylation, and, the, expression, of, transcription, factors])]). relacion([sujeto(['IL-4', and, 'STAT6']), verbo([mediate]), complemento(['T(H)2', responses, in, 'T', cells, and, immunoglobulin, 'class-switching', to, 'IgE', in, 'B', cells])]). relacion([sujeto(['Both', 'T(H)2', responses, and, 'IgE']), verbo([promote]), complemento([the, asthmatic, condition])]). relacion([sujeto(['We']), verbo([have]), complemento([previously, demonstrated, that, poly, '(', 'ADP-ribose)', polymerase, '(', 'PARP)', 14, ',', a, member, of, the, 'PARP', family, of, 'proteins,', regulates, the, transcription, function, of, 'STAT6'])]). relacion([sujeto(['Here', we, investigate, the, role, of, 'PARP-14', and, the, enzyme, activity]), verbo([associated]), complemento([with, it, in, a, model, of, 'AAD', dependent, on, airway, hyperresponsiveness, and, lung, inflammation])]). relacion([sujeto(['We', also, elucidate, the, mechanism, by, which, 'PARP-14']), verbo([regulates]), complemento(['AAD'])]). relacion([sujeto(['Mechanistically,', our, data, indicate, that, 'PARP-14', and, its, enzyme, activity, aid, in, the, differentiation, of, 'T', cells, toward, a, 'T(H)2', phenotype, by]), verbo([regulating]), complemento([the, binding, of, 'STAT6', to, the, 'Gata3', promoter])]). relacion([sujeto(['PARP-14', and, the, catalytic, activity]), verbo([associated]), complemento([with, it, promote, 'T(H)2', differentiation, and, 'AAD', in, a, murine, 'model,', and, targeting, 'PARP-14', might, be, a, potential, new, therapy, for, allergic, asthma])]). relacion([sujeto(['IL-4', produced, by, 'Th2', cells, can, block, cytokine, production, by, 'Th1', 'cells,', and, 'Th1', 'IFN-γ', is, known, to, counterregulate, 'Th2', immune, 'response,']), verbo([inhibiting]), complemento([allergic, eosinophilia])]). relacion([sujeto(['We']), verbo([suggest]), complemento([that, the, attenuated, allergic, lung, inflammation, observed, in, intrauterine, undernourished, rats, is, related, to, an, altered, 'Th1/Th2', cytokine, balance, resulting, from, a, reduced, 'GATA-3/T-bet', ratio])]). relacion([sujeto(['To', investigate, the, role, of, immunological, parameters, in, tumorigenesis, of, cervical, cancer, in, women, infected, with, high, risk, human, papillomavirus, '(', 'hr-HPV),', and, determine, whether, key, findings, with, human, material, can, be, recapitulated, in, the, mouse, 'TC1', carcinoma, model, which]), verbo([expresses]), complemento(['hr-HPV', epitopes])]). relacion([sujeto(['The', mucosa, was, infiltrated, by, 'CD20+', and, 'CD138+', cells, already, at, cervical, intraepithelial, neoplasia, 1, '(', 'CIN1)', and, infiltration]), verbo([increased]), complemento([in, cervical, intraepithelial, neoplasia, 3, '(', 'CIN3)/carcinoma', in, situ, '(', 'CIS)', and, invasive, cervical, cancer, '(', 'ICC),', where, it, strongly, correlated, with, infiltration, by, 'CD32B+', and, 'FoxP3+', lymphocytes])]). relacion([sujeto(['GATA3+', and, 'T-bet+', lymphoid, cells, were]), verbo([increased]), complemento([in, 'ICC', compared, to, 'normal,', and, expression, in, epithelial, cells, of, the, 'Th2', 'inflammation-promoting', cytokine, 'TSLP', and, of, 'IDO1', was, higher, in, 'CIN3/CIS', and, 'ICC'])]). relacion([sujeto(['Finally', we, demonstrated, in, the, mouse, 'TC1', 'carcinoma,', which]), verbo([expresses]), complemento(['hr-HPV', 'epitopes,', an, increase, of, cells, expressing, 'B', cell, or, plasma, cell, markers, or, 'Fc', receptors, in, 'tumor-draining', than, distal, lymph, nodes, or, spleen])]). relacion([sujeto(['hr-HPV', initiates, a, local, 'Th2', inflammation, at, an, early, 'stage,']), verbo([involving]), complemento([antibody, forming, 'cells,', and, fosters, an, immunosuppressive, microenvironment, that, aids, tumor, progression])]). relacion([sujeto(['Several', studies]), verbo([provided]), complemento([evidence, of, innate, interferons, '(', 'IFNs)', regulating, 'T(H)2', cytokine, production, using, purified, 'CD4(+)', memory, cells, and, 'T(H)2', polarisation, via, 'interleukin-4', '(', 'IL-4)'])]). relacion([sujeto(['Quantitative', 'PCR', '(', 'qPCR)', was, used, to, investigate, induction, of, genes]), verbo([involved]), complemento([in, control, of, 'T(H)2', cytokines])]). relacion([sujeto(['IFN-λ', had, no, consistent, effect, on, 'T(H)2', production, except, in, the, presence, of, 'RV', '(', multiplicity, of, 'infection=5);', a]), verbo([decrease]), complemento([in, 'IL-5', alone, was, observed, in, the, presence, of, trivalent, inactivated, influenza, vaccine])]). relacion([sujeto(['GATA']), verbo([binding]), complemento([protein, 3, '(', 'GATA3)', and, suppressors, of, cytokine, signalling3, mRNA, were, differentially, regulated, in, 'HDM', and, 'influenza-stimulated', 'cultures±IFN-β'])]). relacion([sujeto(['However,', a, role, 'for FoxM1', in]), verbo([regulating]), complemento([mammary, differentiation, was, not, known])]). relacion([sujeto(['Here,', we, identify, another, function, of, 'FoxM1,', the, ability, to]), verbo([act]), complemento([as, a, transcriptional, 'repressor,', which, plays, an, important, role, in, regulating, the, differentiation, of, luminal, epithelial, progenitors])]). relacion([sujeto(['Regeneration', of, mammary, glands, with, elevated, levels, of, 'FoxM1']), verbo([leads]), complemento([to, aberrant, ductal, morphology, and, expansion, of, the, luminal, progenitor, pool])]). relacion([sujeto(['FoxM1']), verbo([mediates]), complemento([these, effects, by, repressing, the, key, regulator, of, luminal, 'differentiation,', 'GATA-3'])]). relacion([sujeto(['Through', association, with, 'DNMT3b,', 'FoxM1']), verbo([promotes]), complemento([methylation, of, the, 'GATA-3', promoter, in, an, 'Rb-dependent', manner])]). relacion([sujeto(['To']), verbo([find]), complemento([additional, susceptibility, loci, for, lung, 'cancer,', we, tested, promising, associations, from, our, previous, 'genome-wide', association, study, '(', 'GWAS)', of, lung, cancer, in, the, 'Chinese', population, in, an, extended, validation, sample, size, of, 7, ',', 436, individuals, with, lung, cancer, '(', 'cases)', and, 7, ',', 483, controls])]). relacion([sujeto(['We']), verbo([found]), complemento(['genome-wide', significant, '(', 'P', &, 'lt;', 5.0, ×, 10, '(', -, 8, ')', ')', evidence, for, three, additional, lung, cancer, susceptibility, loci, at, 10, p14, '(', 'rs1663689,', close, to, 'GATA3,', 'P', =, 2.84, ×, 10, '(', -, 10, ')', ')', ',', 5, q32, '(', rs2895680, in, 'PPP2R2B-STK32A-DPYSL3,', 'P', =, 6.6, ×, 10, '(', -, 9, ')', ')', and, 20, q13])]). relacion([sujeto(['We', also]), verbo([found]), complemento([consistent, associations, for, rs247008, at, 5, q31])]). relacion([sujeto(['Ipilimumab']), verbo([induces]), complemento(['long-lasting', clinical, responses, in, a, minority, of, patients, with, metastatic, melanoma])]). relacion([sujeto(['To', better, understand, the, 'mechanism(s)', of, action, and, to, identify, novel, biomarkers]), verbo([associated]), complemento([with, the, clinical, benefit, and, toxicity, of, 'ipilimumab,', baseline, characteristics, and, changes, in, 'CD4(+)', and, 'CD8(+)', 'T', cells, from, melanoma, patients, receiving, ipilimumab, were, characterized, by, gene, profiling, and, flow, cytometry])]). relacion([sujeto(['Microarray', analysis, of, 'flow-cytometry', purified, 'CD4(+)', and, 'CD8(+)', 'T', cells, was, employed, to, assess, gene, profiling, changes]), verbo([induced]), complemento([by, ipilimumab])]). relacion([sujeto(['Ipilimumab', 'up-regulated', 'Ki67', and, 'ICOS', on, 'CD4(+)', and, 'CD8(+)', cells, at, both, 3, -, and, 6, -, month, post, ipilimumab, '(', p, '≤', 0.001, ')', ',']), verbo([decreased]), complemento(['CCR7', and, 'CD25', on, 'CD8(+)', at, 3, -, month, post, ipilimumab, '(', p, '≤', 0.02, ')', ',', and, increased, 'Gata3', in, 'CD4(+)', and, 'CD8(+)', cells, at, 6, -, month, post, ipilimumab, '(', p, '≤', 0.001, ')'])]). relacion([sujeto(['Increased', 'EOMES(+)CD8(+),', 'GranzymeB(+)EOMES(+)CD8(+)', and]), verbo([decreased]), complemento(['Ki67(+)EOMES(+)CD4(+)', 'T', cells, at, 6, months, were, significantly, associated, with, relapse, '(', all, p, '≤', 0.03, ')'])]). relacion([sujeto(['Decreased', 'Ki67(+)CD8(+)', 'T', cells, were, significantly]), verbo([associated]), complemento([with, the, development, of, irAE, '(', p, =, 0.02, ')'])]). relacion([sujeto(['At', 'baseline,', low, 'Ki67(+)EOMES(+)CD8(+)', 'T', cells, were]), verbo([associated]), complemento([with, relapse, '(', p, '≤', 0.001, ')', ',', and, low, 'Ki67(+)EOMES(+)CD4(+)', 'T', cells, were, associated, with, irAE, '(', p, '≤', 0.008, ')'])]). relacion([sujeto(['Ki67(+)EOMES(+)CD8(+)', and, 'Ki67(+)EOMES(+)CD4(+)T', cells, at, baseline, merit, further, testing, as, biomarkers]), verbo([associated]), complemento([with, outcome, and, 'irAEs,', respectively])]). relacion([sujeto(['Distinct', types, of, effector, 'T', cells]), verbo([have]), complemento([different, functions, in, adaptive, immune, responses])]). relacion([sujeto(['Th1', cells, play, important, roles, in, the, control, of, intracellular, bacteria, by, producing, 'IFN-γ', to]), verbo([activate]), complemento([macrophages, and, in, 'anti-viral', immunity, by, producing, 'IFN-γ', and, activating, cytotoxic, 'T', lymphocytes])]). relacion([sujeto(['Th2', 'cell-derived', cytokines, are, important, in]), verbo([activating]), complemento([mast, 'cells,', 'eosinophils,', and, goblet, cells, in, 'anti-helminth', immunity])]). relacion([sujeto(['Th17', cells, are, pivotal, for, the, inflammatory, response]), verbo([mediated]), complemento([by, 'neutrophils,', which, resists, extracellular, bacterial, infection])]). relacion([sujeto(['Recent', studies]), verbo([have]), complemento([identified, multiple, subsets, in, innate, lymphocytes, corresponding, to, previously, defined, 'Th', subsets])]). relacion([sujeto(['In', 'addition,', these, cells, are, likely]), verbo([involved]), complemento([in, the, pathophysiology, of, some, types, of, allergic, diseases])]). relacion([sujeto(['Churg-Strauss', syndrome, '(', 'CSS)', is, a, rare, systemic, vasculitis]), verbo([associated]), complemento([with, eosinophilia, and, asthma])]). relacion([sujeto(['In', active, 'CSS,', both, 'BALF', and, blood, eosinophil, counts, were]), verbo([increased]), complemento(['(', 'P<0'])]). relacion([sujeto(['BALF', cells, in, active, disease, were, characterized, by, an]), verbo([increased]), complemento([expression, of, 'Th2', and, 'regulatory-type', 'transcripts:', 'STAT6,', 'STAT3,', 'GATA3,', 'IL4,', 'IL5', and, 'IL10', as, compared, with, 'asthmatics,', and, 'STAT5A,', 'CCR4,', 'FOXP3,', 'IL4,', 'IL5', and, 'IL10', when, compared, with, inactive, 'CSS'])]). relacion([sujeto(['There', was, significant]), verbo([increase]), complemento([in, 'BALF', concentration, of, 'IL-5', and, 'CCL26', in, exacerbation, of, 'CSS'])]). relacion([sujeto(['We']), verbo([found]), complemento([a, strong, positive, correlation, between, clinical, parameters, of, disease, activity, '(', 'BVAS,', 'eosinophilia)', and, expression, of, 'IL4,', 'IL5,', 'IL10', and, 'STAT5A'])]). relacion([sujeto(['These', results, indicate, that, as, compared, with, 'asthma,', 'active-CSS', patients]), verbo([have]), complemento([much, stronger, local, 'Th2', response, in, the, airways])]). relacion([sujeto(['The', 'Th2', locus, control, region, '(', 'LCR)']), verbo([has]), complemento([been, shown, to, be, a, crucial, 'cis-acting', element, for, 'Th2', cytokine, expression, and, 'Th2', cell, differentiation])]). relacion([sujeto(['We']), verbo([found]), complemento(['IFN-γ', to, be, aberrantly, 'up-regulated'])]). relacion([sujeto(['In', 'addition,', histone, 3, '(', 'H3)-acetylation', and, histone, 3, lysine, 4, '(', 'H3-K4)-methylation', greatly]), verbo([increased]), complemento([at, the, ifng, locus, of, the, 'Th2', cells])]). relacion([sujeto(['GATA-3', and, 'STAT6']), verbo([bound]), complemento([to, the, ifng, promoter, in, 'Th2', cells, from, the, wild, type, but, not, from, the, 'Th2', 'LCR-deficient', 'mice,', and, they, directly, repressed, ifng, expression, in, transient, reporter, assay])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, expression, of, the, ifng, gene, and, chromatin, remodeling, of, the, ifng, locus, are, under, the, control, of, a, 'Th2', 'LCR-mediated', 'Th2', differentiation, program])]). relacion([sujeto(['Vaccination', remains, one, of, the, most, effective, approaches, to]), verbo([prevent]), complemento([the, spread, of, infectious, diseases])]). relacion([sujeto(['Immune', responses, to, vaccination, can, be]), verbo([enhanced]), complemento([by, inclusion, of, adjuvant, in, a, vaccine])]). relacion([sujeto(['Paclitaxel', extracted, from, the, bark, of, the, 'Pacific', yew, tree, 'Taxus', brevifola, was, previously, demonstrated, to]), verbo([have]), complemento([adjuvant, property])]). relacion([sujeto(['To', investigate, the, adjuvant, effect, of, this, 'compound,', we, measured, the, immune, responses]), verbo([induced]), complemento([by, 'co-administration', of, a, split, inactivated, influenza, 'H1N1', vaccine, antigen, with, docetaxel])]). relacion([sujeto(['When', 'co-administered', with, 'docetaxel,', lower, dose, antigen, '(', equivalent, to, 10, ng, 'HA)']), verbo([induced]), complemento([similar, levels, of, 'IgG', and, 'IgG', isotypes, as, well, as, 'HI', titers, to, those, induced, by, higher, dose, antigen, '(', equivalent, to, 100, ng, 'HA)'])]). relacion([sujeto(['Docetaxel']), verbo([promoted]), complemento([splenocyte, responses, to, 'H1N1', 'antigen,', 'ConA', and, 'LPS,', mRNA, expressions, of, cytokines, '(', 'IFN-gamma,', 'IL-12,', 'IL-4', and, 'IL-10)', and, 'T-bet/GATA-3', by, splenocytes])]). relacion([sujeto(['The']), verbo([enhanced]), complemento([immunity, was, associated, with, 'up-expressed', microRNAs, '(', 'miR-155,', 'miR-150', and, 'miR-146a)', in, 'docetaxel-stimulated', 'RAW264'])]). relacion([sujeto(['Docetaxel']), verbo([promoted]), complemento([similar, 'IgE', level, to, but, alum, promoted, significantly, higher, 'IgE', level, than, the, control])]). relacion([sujeto(['Docetaxel']), verbo([has]), complemento([adjuvant, effect, on, the, influenza, 'H1N1', vaccine, by, 'up-regulation', of, 'Th1/Th2', immune, responses])]). relacion([sujeto(['The', aim, of, this, study, was, to, investigate, the, clinicopathological, characteristics, of, 'GATA']), verbo([binding]), complemento([protein, 3, '(', 'GATA3)-positive', breast, cancers, as, well, as, the, association, of, 'GATA3', expression, with, response, to, chemotherapy])]). relacion([sujeto(['Somatic', mutations, were]), verbo([found]), complemento([in, only, three, tumors])]). relacion([sujeto(['Interestingly,', 'GATA3', was, an, independent, predictor, of, response, to, 'chemotherapy,']), verbo([suggesting]), complemento([that, 'GATA3', might, be, clinically, useful, as, a, predictor, of, a, poor, response, to, chemotherapy])]). relacion([sujeto(['To', observe, the, effect, of, moxibustion, pretreatment, on, the, expression, of, leukocytic, 'T-box', transcription, factor]), verbo([expressed]), complemento([in, 'T', cells, '(', 'T-bet)', mRNA, and, 'trans-acting', 'T-cell-specific', transcription, factor, 'GATA-3', mRNA, in, athletes, undergoing, heavy, load, 'training,', so, as, to, study, its, mechanism, underlying, prevention, of, imbalance, of, immune, function])]). relacion([sujeto(['In', comparison, with, 'pre-training,', the, expression, levels, of, leukocytic, 'T-bet', mRNA, were]), verbo([increased]), complemento([slightly, after, heavy, load, running, training, '(', 7.24, '%', ',', 16.84, '%', ')', and, after, adjustment, training, '(', 4.52, '%', ',', 14.8, '%', ')', in, both, control, and, treatment, groups, '(', 'P', &, 'gt;', 0.05, ')'])]). relacion([sujeto(['The', ratios, of, leukocytic, 'T-bet', 'mRNA/GATA-3', mRNA, were]), verbo([increased]), complemento([by, 13.58, '%', and, 75.16, '%', after, heavy, load, running, training, and, decreased, by, 29.63, '%', and, increased, by, 35.4, '%', ',', respectively, after, adjustment, training, in, the, control, and, treatment, groups, in, comparison, with, 'pre-training'])]). relacion([sujeto(['No', significant, differences, were]), verbo([found]), complemento([between, two, groups, in, the, expression, levels, of, 'T-bet', mRNA, and, the, ratios, of, 'T-bet', 'mRNA/GATA-3', mRNA, at, the, 3, 'time-points,', and, in, the, expression, levels, of, 'GATA-3', mRNA, before, and, after, heavy, load, running, training, '(', 'P', &, 'gt;', 0.05, ')'])]). relacion([sujeto(['Moxibustion', pretreatment, can]), verbo([inhibit]), complemento([the, expression, of, leukocytic, 'GATA-3', mRNA, after, adjustment, training, in, the, 'middle-long', distance, heavy, load, running, 'athletes,', which, may, contribute, to, its, effect, in, regulating, imbalance, of, 'Th', 1, /, 'Th', 2, after, heavy, load, training])]). relacion([sujeto(['The', 'TE', molecular, signature, included, 2, ',', 196, 'transcripts,', among, which, were, genes, already, known, to, be, 'TE-specific', '(', 'GATA2,', 'GATA3', and, 'GCM1)', but, also, genes]), verbo([involved]), complemento([in, trophoblast, invasion, '(', 'MUC15),', chromatin, remodeling, '(', specifically, the, 'DNA', methyltransferase, 'DNMT3L)', and, steroid, metabolism, '(', 'HSD3B1,', 'HSD17B1', and, 'FDX1)'])]). relacion([sujeto(['This', study]), verbo([provides]), complemento([a, comprehensive, outlook, of, the, genes, that, are, expressed, during, the, initial, 'embryo-trophectoderm', transition, in, humans])]). relacion([sujeto(['Further', understanding, of, the, biological, functions, of, the, key, genes]), verbo([involved]), complemento([in, steroidogenesis, and, epigenetic, regulation, of, transcription, that, are, 'up-regulated', in, 'TE', cells, may, clarify, their, contribution, to, 'TE', specification, and, might, also, provide, new, biomarkers, for, the, selection, of, viable, and, competent, blastocysts])]). relacion([sujeto(['Sox4', is, a, transcription, factor, that]), verbo([regulates]), complemento([various, developmental, processes])]). relacion([sujeto(['Here', we, show, that, 'Sox4', was]), verbo([induced]), complemento([by, 'TGF-β', and, negatively, regulated, the, transcription, factor, 'GATA-3,', the, master, regulator, of, function, of, 'T', helper, type, 2, '(', 'T(H)2)', 'cells,', by, two, distinct, mechanisms])]). relacion([sujeto(['First,', 'Sox4']), verbo([bound]), complemento([directly, to, 'GATA-3,', preventing, its, binding, to, 'GATA-3', consensus, 'DNA', sequences])]). relacion([sujeto(['Second,', 'Sox4']), verbo([bound]), complemento([to, the, promoter, region, of, the, gene, encoding, interleukin, 5, '(', 'IL-5),', a, 'T(H)2', 'cytokine,', and, prevented, binding, of, 'GATA-3', to, this, promoter])]). relacion([sujeto(['T(H)2', 'cell-driven', airway, inflammation, was]), verbo([modulated]), complemento([by, alterations, in, 'Sox4', expression])]). relacion([sujeto(['Thus,', 'Sox4']), verbo([acted]), complemento([as, a, downstream, target, of, 'TGF-β', to, inhibit, 'GATA-3', 'function,', 'T(H)2', differentiation, and, 'T(H)2', 'cell-mediated', inflammation])]). relacion([sujeto(['The', diagnosis, of, diffuse, pontine, tumors]), verbo([has]), complemento([largely, been, made, on, the, basis, of, 'MRI', since, the, early, 1990, s])]). relacion([sujeto(['In', cases, of, tumors, considered, &, 'quot;typical,"', as, a, 'rule,', no, biopsy, specimen]), verbo([has]), complemento([been, 'obtained,', and, the, tumors, have, been, considered, diffuse, intrinsic, pontine, gliomas, '(', 'DIPGs)'])]). relacion([sujeto(['There']), verbo([have]), complemento([been, sporadic, reports, that, primitive, neuroectodermal, tumors, '(', 'PNETs)', of, the, pons, may, not, be, distinguishable, from, the, 'DIPGs', by, radiological, imaging])]). relacion([sujeto(['Thirty-eight', 'genes,', including, 'GATA3,', are, uniquely, differentially]), verbo([expressed]), complemento([in, pontine, 'PNETs', compared, with, other, types, of, pediatric, brain, 'tumors,', including, 'DIPGs', and, other, 'PNETs', at, a, false, discovery, rate, statistical, significance, of, less, than, 0.05])]). relacion([sujeto(['The', 2, pontine, 'PNET', cases, cluster, with, supratentorial, 'PNETs,', rather, than, with, 'DIPGs,']), verbo([suggesting]), complemento([that, these, tumors, should, be, treated, with, a, 'PNET', 'regimen,', not, with, 'DIPG', therapy])]). relacion([sujeto(['The', long, control, region, '(', 'LCR)', of, human, papillomavirus, '(', 'HPV)']), verbo([regulates]), complemento([early, gene, transcription, by, interaction, with, several, viral, and, cellular, transcription, factors, '(', 'TFs)'])]). relacion([sujeto(['Among', the, 704, 'TFs', 'tested,', 28]), verbo([activated]), complemento([and, 36, inhibited, the, 'LCR', of, 'HPV-18', by, more, than, 2, -, fold])]). relacion([sujeto(['For', 'validation,', 'C33', cells, were, cotransfected, with]), verbo([increasing]), complemento([amounts, of, selected, 'TF', expression, plasmids, in, addition, to, 'LCR-luciferase', vectors, of, different, molecular, variants, of, 'HPV-18', and, 'HPV-16'])]). relacion([sujeto(['Among', the, 'TFs', 'identified,', only, 'GATA3,', 'FOXA1,', and, 'MYC']), verbo([have]), complemento([putative, binding, sites, within, the, 'LCR', 'sequence,', as, indicated, using, the, 'TRANSFAC', database])]). relacion([sujeto(['Furthermore,', we, demonstrated, 'FOXA1', and, 'MYC', in, vivo]), verbo([binding]), complemento([to, the, 'LCR', of, both, 'HPV', types, using, chromatin, immunoprecipitation, assay])]). relacion([sujeto(['Many', of, these, factors, are, mutated, in, cancer, or, are, putative, cancer, biomarkers, and, could, potentially, be]), verbo([involved]), complemento([in, the, regulation, of, 'HPV', early, gene, expression])]). relacion([sujeto(['Univariate', 'Cox', regression, analysis, showed, that, lymph, node, 'metastasis,', distant, 'metastasis,', 'TNM', 'staging,', lymphovascular, 'invasion,', 'GNLY', mRNA, 'expression,', and, the, overall, expression, level, of, the, 8, types, of, 'Th1', cells, were]), verbo([associated]), complemento([with, the, prognosis, of, patients, with, gastric, 'cancer(all', 'P<0'])]). relacion([sujeto(['The', 3, -, year, survival, was, 86.2, '%', in, patients, with]), verbo([increased]), complemento([expression, of, mRNA, and, 58.6, '%', in, those, with, decreased, expression])]). relacion([sujeto(['The', 3, -, year, survival, was, 79.6, '%', in, patients, with, any]), verbo([increase]), complemento([in, the, 8, 'Th1', cytokines, and, 33.3, '%', in, those, with, consistent, downregulation, of, the, 8, cytokines])]). relacion([sujeto(['Multivariate', 'Cox', analysis, showed, that, lymph, node, metastasis, and, the, overall, expression, level, of, 8, 'Th1', cytokines, were, independent, risk, factors]), verbo([associated]), complemento([with, the, prognosis, of, patients, with, gastric, cancer, in, this, 'cohort(both', 'P<0'])]). relacion([sujeto(['The', mRNA, expression, of, 'GNLY', is]), verbo([associated]), complemento([with, the, prognosis, of, patients, with, gastric, cancer, but, is, not, an, independent, risk, factor])]). relacion([sujeto(['Breast', carcinoma, is, the]), verbo([leading]), complemento([cause, of, 'cancer-related', mortality, in, women, 'worldwide,', with, an, estimated, 1.38, million, new, cases, and, 458, ',', 0, deaths, in, 2008, alone])]). relacion([sujeto(['Recurrent', somatic, alterations, in, breast, cancer]), verbo([have]), complemento([been, 'described,', including, mutations, and, copy, number, 'alterations,', notably, 'ERBB2', 'amplifications,', the, first, successful, therapy, target, defined, by, a, genomic, aberration])]). relacion([sujeto(['Previous', 'DNA', sequencing, studies, of, breast, cancer, genomes]), verbo([have]), complemento([revealed, additional, candidate, mutations, and, gene, rearrangements])]). relacion([sujeto(['Here', we]), verbo([report]), complemento([the, 'whole-exome', sequences, of, 'DNA', from, 103, human, breast, cancers, of, diverse, subtypes, from, patients, in, 'Mexico', and, 'Vietnam', compared, to, 'matched-normal', 'DNA,', together, with, 'whole-genome', sequences, of, 22, breast, 'cancer/normal', pairs])]). relacion([sujeto(['Furthermore,', we]), verbo([have]), complemento([identified, a, recurrent, 'MAGI3-AKT3', fusion, enriched, in, 'triple-negative', breast, cancer, lacking, oestrogen, and, progesterone, receptors, and, 'ERBB2', expression])]). relacion([sujeto(['The', 'MAGI3-AKT3', fusion]), verbo([leads]), complemento([to, constitutive, activation, of, 'AKT', 'kinase,', which, is, abolished, by, treatment, with, an, 'ATP-competitive', 'AKT', 'small-molecule', inhibitor])]). relacion([sujeto(['Mutant', 'MAP3K1', was]), verbo([associated]), complemento([with, luminal, 'A', 'status,', 'low-grade', histology, and, low, proliferation, 'rates,', whereas, mutant, 'TP53', was, associated, with, the, opposite, pattern])]). relacion([sujeto(['Distinct', phenotypes, in, 'oestrogen-receptor-positive', breast, cancer, are]), verbo([associated]), complemento([with, specific, patterns, of, somatic, mutations, that, map, into, cellular, pathways, linked, to, tumour, 'biology,', but, most, recurrent, mutations, are, relatively, infrequent])]). relacion([sujeto(['Prospective', clinical, trials, based, on, these, findings, will]), verbo([require]), complemento([comprehensive, genome, sequencing])]). relacion([sujeto(['GOLPH2', is, a, highly]), verbo([conserved]), complemento([protein])]). relacion([sujeto(['We', describe, the, isolation, and, characterization, of, 'Xenopus', 'golph2,', which]), verbo([dimerizes]), complemento([and, localizes, to, the, 'Golgi', in, a, manner, similar, to, human, 'GOLPH2'])]). relacion([sujeto(['Xenopus', golph2, is]), verbo([expressed]), complemento([in, the, pronephros, during, early, development])]). relacion([sujeto(['Additionally,', 'Nephrin', expression, is]), verbo([enhanced]), complemento([in, the, 'glomus,', and, the, expression, of, pronephric, marker, 'genes,', such, as, 'atp1b1,', 'ClC-K,', 'NKCC2,', and, 'NBC1,', is, diminished, in, the, tubules, and, duct])]). relacion([sujeto(['Expression', patterns, of, the, transcription, factors, 'WT1,', 'Pax2,', 'Pax8,', 'Lim1,', 'GATA3,', and, 'HNF1β', are, also, examined, in, the, golph2, knockdown, 'embryos,', the, expression, of, 'WT1', is]), verbo([increased]), complemento([in, the, glomus, and, expanded, laterally, in, the, pronephric, region])]). relacion([sujeto(['We', conclude, that, the, deletion, of, golph2]), verbo([causes]), complemento([an, increase, in, the, expression, of, 'WT1,', which, may, promote, glomus, formation, and, inhibit, pronephric, tubule, differentiation])]). relacion([sujeto(['SATB1']), verbo([mediates]), complemento(['Wnt', signaling, by, recruiting, 'β-catenin', to, its, genomic, targets, and, coordinates, 'T', helper, type, 2, '(', 'T(H)2)', differentiation, by, positively, regulating, 'GATA-3'])]). relacion([sujeto(['We', discuss, how, regulation, of, the, activity, of, 'SATB1']), verbo([has]), complemento([a, critical, role, in, driving, these, two, important, differentiation, pathways, in, 'T', cells])]). relacion([sujeto(['GATA3', expression]), verbo([has]), complemento([been, reported, in, urothelial, and, breast, 'carcinomas;', 'however,', the, published, data, on, 'GATA3', expression, in, tumors, from, other, organs, are, limited])]). relacion([sujeto(['Tumor', necrosis, 'factor-α', converting, enzyme, '(', 'TACE),', also, known, as, 'A', disintegrin, and, metalloproteinase, 17, ',', is, a, proteolytic, enzyme, that]), verbo([regulates]), complemento([a, variety, of, cell, surface, molecules, including, 'TNF-α,', via, ectodomain, shedding])]). relacion([sujeto(['We']), verbo([found]), complemento(['TACE', expression, on, mouse, 'HFs', and, conditionally, depleted, it, in, cells, that, expressed, 'sex-determining', region, 'Y-related', 'high-mobility-group', box, 9, '(', 'SOX9)', transcription, 'factor,', an, 'HF', stem, cell, transcription, factor, '(', 'Tace(flox/flox)', -, 'Sox9-Cre,', 'hereafter,', &, 'quot;Tace/Sox9")'])]). relacion([sujeto(['They', underwent, 'diffuse,', 'progressive,', and, ultimately, 'whole-body', hair]), verbo([loss]), complemento([by, 20, weeks, old])]). relacion([sujeto(['In', vitro, 'colony-forming', capacity, was, abolished, in, 'Tace/Sox9', 'keratinocytes,', and, 'HFs', exhibited]), verbo([increased]), complemento([proliferation, in, 'situ,', collectively, demonstrating, that, 'Tace/Sox9', mice, failed, to, establish, the, bulge, niche, and, to, maintain, &, 'quot;stemness"', of, 'HF', stem, cells])]). relacion([sujeto(['This', study]), verbo([provides]), complemento([mechanistic, implication, for, human, 'TACE-deficiency', and, for, hair, abnormality, caused, by, 'EGFR', inhibitors])]). relacion([sujeto(['Instead,', it]), verbo([has]), complemento([opposite, effects, on, 'T-bet', and, 'Gata3', expression, 'and,', 'hence,', on, 'Th1', and, 'Th2', differentiation])]). relacion([sujeto(['Alternatively,', in, the, presence, of, 'TGF-β,', the, 'Erk', pathway]), verbo([suppresses]), complemento([a, large, program, of, gene, 'expression,', effectively, limiting, the, differentiation, of, 'Foxp3(+)', regulatory, 'T', cells])]). relacion([sujeto(['In', the, latter, 'case,', the, mechanisms]), verbo([involved]), complemento([include, suppression, of, 'Gata3', and, 'Foxp3,', induction, of, 'Tbx21,', phosphorylation, of, 'Smad2,3,', and, possibly, suppression, of, 'Socs2,', a, positive, inducer, of, 'Stat5', signaling])]). relacion([sujeto(['Consequently,']), verbo([loss]), complemento([of, 'Erk2', severely, impeded, 'Th1', differentiation, while, enhancing, the, development, of, 'Foxp3(+)-induced', 'T', regulatory, cells])]). relacion([sujeto(['Glutamatergic', neurons, are]), verbo([required]), complemento([for, the, generation, and, inhibitory, neurons, for, the, patterning, of, the, motor, activity, associated, with, repetitive, motor, behaviors])]). relacion([sujeto(['We']), verbo([find]), complemento(['that,', following, the, ablation, of, 'V2a', 'neurons,', newborn, mice, breathe, at, a, lower, frequency])]). relacion([sujeto(['Thus,', neurons, of, the, embryonic, 'V2a', lineage, appear, to]), verbo([have]), complemento([been, recruited, to, neural, networks, that, control, breathing, and, 'locomotion,', two, prominent, 'CPG-driven,', repetitive, motor, behaviors])]). relacion([sujeto(['We']), verbo([have]), complemento([investigated, the, inflammatory, infiltrate, in, 'post-transplant', 'dn-AIH,', a, form, of, late, insidious, graft, 'rejection,', focusing, on, transcription, factors, defining, effector, and, 'T-regs,', using, an, antigen, retrieval, immunohistochemical, method, on, archived, liver, 'tissue,', and, compared, it, with, 'ACR', and, classical, 'AIH'])]). relacion([sujeto(['A', tight, balance, between, these, different, subsets]), verbo([ensures]), complemento([proper, control, of, the, immune, response])]). relacion([sujeto(['There', is]), verbo([increasing]), complemento([evidence, revealing, an, important, role, for, 'Notch', signaling, in, the, regulation, of, 'CD4⁺T', helper, cell, differentiation, or, function, in, the, periphery])]). relacion([sujeto(['However,', the, exact, mechanisms]), verbo([involved]), complemento([remain, unclear, and, appear, contradictory])]). relacion([sujeto(['And', the, medicine, patch, group, surpassed, the, other, 2, groups, in, controlling, the, number, of, attacks, and]), verbo([increasing]), complemento([the, asymtomatic, days, '(', 'P', &, 'lt;', 0.05, ',', 'P', &, 'lt;', 0.01, ')'])]). relacion([sujeto(['The', level, of, 'IgE', and, 'IL-4', of, all, the, 3, groups]), verbo([decreased]), complemento([sharply, after, the, treatment, '(', 'P', &, 'lt;', 0.05, ',', 'P', &, 'lt;', 0.01, ')'])]). relacion([sujeto(['The', level, of, 'GATA-3', mRNA, was, obviously, 'decreased,', while, the, level, of, 'T-bet', mRNA, was, obviouly]), verbo([increased]), complemento([in, the, medicine, patch, and, medicinal, vesiculation, groups, '(', 'P', &, 'lt;', 0.05, ',', 'P', &, 'lt;', 0.01, ')'])]). relacion([sujeto(['And', the, medicine, patch, group, had, obvious, superiority, on]), verbo([increasing]), complemento([the, level, of, 'T-bet', mRNA, when, compared, with, the, medicinal, vesiculation, and, western, medicine, groups, '(', 'P', &, 'lt;', 0.01, ',', 'P', &, 'lt;', 0.05, ')'])]). relacion([sujeto(['It', is, concluded, that, the, new, percutaneous, absorption, herbal, patch]), verbo([has]), complemento([exact, effect, on, asthma])]). relacion([sujeto(['GABAergic', neurons, in, the, ventral, mesodiencephalic, region, are, highly, important, for, the, function, of, dopaminergic, pathways, that]), verbo([regulate]), complemento([multiple, aspects, of, behavior])]). relacion([sujeto(['We', recently, showed, that, molecular, regulation, of, differentiation, of, the, 'GABAergic', neurons]), verbo([associated]), complemento([with, the, dopaminergic, nuclei, in, the, ventral, midbrain, '(', 'VTA', and, 'SNpr)', is, distinct, from, the, rest, of, 'midbrain,', but, the, reason, for, this, difference, remained, elusive])]). relacion([sujeto(['Here,', we]), verbo([have]), complemento([analyzed, the, developmental, origin, of, the, 'VTA', and, 'SNpr', 'GABAergic', neurons, by, genetic, fate, mapping])]). relacion([sujeto(['A', failure, in, 'GABAergic', neuron, differentiation, in, this, region, correlates, with]), verbo([loss]), complemento([of, 'VTA', and, 'SNpr', 'GABAergic', neurons, in, 'Tal1', mutant, mice])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([unique, migratory, pathways, for, the, precursors, of, important, 'GABAergic', neuron, 'subpopulations,', and, provide, the, basis, for, understanding, diversity, within, midbrain, 'GABAergic', neurons])]). relacion([sujeto(['Although', 'GATA']), verbo([binding]), complemento([protein, 3, ',', a, zinc, finger, transcription, factor, and, an, estrogen, 'receptor-regulated', 'gene,', has, recently, been, suggested, as, a, marker, for, 'urothelium,', prognostic, significance, of, 'GATA', binding, protein, 3, expression, in, bladder, tumor, remains, unclear])]). relacion([sujeto(['We', immunohistochemically, stained, for, 'GATA']), verbo([binding]), complemento([protein, 3, in, urothelial, neoplasm, and, matched, nonneoplastic, bladder, tissue, specimens])]). relacion([sujeto(['GATA']), verbo([binding]), complemento([protein, 3, was, positive, in, 125, '(', 86, '%', ;, 13, '[', 9, '%', ']', 'weak,', 44, '[', 30, '%', ']', 'moderate,', and, 68, '[', 47, '%', ']', 'strong)', of, 145, bladder, 'tumors,', which, was, significantly, lower, than, in, benign, urothelium, '(', 104, /, 106, '[', 98, '%', ']', ;, 3, '[', 3, '%', ']', 'weak,', 30, '[', 28, '%', ']', 'moderate,', and, 71, '[', 67, '%', ']', 'strong)', '(', 'P='])]). relacion([sujeto(['Fifty', '(', 98, '%', ')', of, 51, 'low-grade', tumors, were, 'GATA']), verbo([binding]), complemento([protein, 3, 'positive,', whereas, 75, '(', 80, '%', ')', of, 94, 'high-grade', carcinomas, were, 'GATA', binding, protein, 3, positive, '(', 'P='])]). relacion([sujeto(['Similarly,', 78, '(', 98, '%', ')', of, 80, 'non-muscle-invasive', tumors]), verbo([expressed]), complemento([the, 'GATA', binding, protein, 3, ',', compared, with, 47, '(', 72, '%', ')', of, 65, 'muscle-invasive', tumors, '(', 'P<'])]). relacion([sujeto(['Conversely,', among, 68, cases, treated, with, 'cystectomy,', significantly, lower, expression, of, 'GATA']), verbo([binding]), complemento([protein, 3, was, found, in, pN0, tumors, '(', 32, /, 47, '[', 68, '%', ']', ')', than, in, 'node-positive', tumors, '(', 20, /, 21, '[', 95, '%', ']', ')', '(', 'P='])]). relacion([sujeto([25, ')', of, 'GATA']), verbo([binding]), complemento([protein, 3, correlated, with, progression, of, 'muscle-invasive', tumors])]). relacion([sujeto(['Multivariate', analysis, identified, high, 'GATA']), verbo([binding]), complemento([protein, 3, expression, as, a, strong, prognosticator, for, progression, '(', 'P='])]). relacion([sujeto(['Moreover,', there, were, significant, correlations, between, 'GATA']), verbo([binding]), complemento([protein, 3, expression, vs, androgen, receptor, 'overexpression,', estrogen, receptor, α, 'overexpression,', or, loss, of, estrogen, receptor, β, expression])]). relacion([sujeto(['Thus,', compared, with, benign, 'urothelium,', a, significant]), verbo([decrease]), complemento([in, the, expression, of, 'GATA', binding, protein, 3, in, urothelial, neoplasms, was, seen])]). relacion([sujeto(['Loss', of, 'GATA']), verbo([binding]), complemento([protein, 3, was, associated, with, 'high-grade', 'and/or', 'muscle-invasive', 'tumors,', whereas, strong, expression, was, an, independent, predictor, of, poor, prognosis])]). relacion([sujeto(['Lineage', commitment, studies, in, mammary, glands]), verbo([have]), complemento([focused, on, identifying, cell, populations, that, display, stem, or, progenitor, properties])]). relacion([sujeto(['However,', the, mechanisms, that, control, cell, fate]), verbo([have]), complemento([been, incompletely, explored])]). relacion([sujeto(['Herein', we, show, that, zinc, finger, protein, 157, '(', 'Zfp157)', is]), verbo([required]), complemento([to, establish, the, balance, between, luminal, alveolar, 'pStat5-', and, 'Gata-3-expressing', cells, in, the, murine, mammary, gland])]). relacion([sujeto(['Using', mice, in, which, the, zfp157, gene, was, 'disrupted,', we]), verbo([found]), complemento([that, alveologenesis, was, accelerated, concomitantly, with, a, dramatic, skewing, of, the, proportion, of, 'pStat5-expressing', cells, relative, to, 'Gata-3⁺', cells])]). relacion([sujeto(['This', suppression, of, the, 'Gata-3⁺', lineage, was]), verbo([associated]), complemento([with, increased, expression, of, the, inhibitor, of, 'helix-loop-helix', protein, 'Id2'])]). relacion([sujeto(['These', data]), verbo([suggest]), complemento([that, the, luminal, alveolar, compartment, of, the, mammary, gland, is, comprised, of, a, number, of, distinct, cell, populations, 'that,', although, 'interdependant,', exhibit, considerable, cell, fate, plasticity])]). relacion([sujeto(['Using', homozygosity, mapping, and, locus, 'resequencing,', we]), verbo([found]), complemento([that, alterations, in, the, homeodomain, of, the, 'IRX5', transcription, factor, cause, a, recessive, congenital, disorder, affecting, 'face,', 'brain,', 'blood,', 'heart,', bone, and, gonad, development])]). relacion([sujeto(['We']), verbo([found]), complemento([through, in, vivo, modeling, in, 'Xenopus', laevis, embryos, that, 'Irx5', modulates, the, migration, of, progenitor, cell, populations, in, branchial, arches, and, gonads, by, repressing, 'Sdf1'])]). relacion([sujeto(['We', further]), verbo([found]), complemento([that, transcriptional, control, by, 'Irx5', is, modulated, by, direct, 'protein-protein', interaction, with, two, 'GATA', 'zinc-finger', 'proteins,', 'GATA3', and, 'TRPS1;', disruptions, of, these, proteins, also, cause, craniofacial, dysmorphisms])]). relacion([sujeto(['Our', findings]), verbo([suggest]), complemento([that, 'IRX', proteins, integrate, combinatorial, transcriptional, inputs, to, regulate, key, signaling, molecules, involved, in, the, ontogeny, of, multiple, organs, during, embryogenesis, and, homeostasis])]). relacion([sujeto(['To', 'date,', it, remains, unclear, whether, exactly, the, same, genetic, mechanism]), verbo([acts]), complemento([in, adult, compared, to, fetal, 'T', cell, development])]). relacion([sujeto(['The', largest, cluster, contained, genes, upregulated, after, transition, through, the, most, primitive, pool, into, the, next, transitory, population, with, a, consistently, elevated, expression, of, elements]), verbo([associated]), complemento([with, ongoing, 'T', cell, fate, 'specification,', like, 'Gata3', and, 'Tcf7,', in, fetal, progenitors])]). relacion([sujeto(['Furthermore,', adult, and, fetal, 'T', cell, progenitors, occupied, distinct, &, 'quot;transcriptional', 'territories"']), verbo([revealed]), complemento([a, precise, land, map, of, the, progression, to, final, 'T', cell, commitment, operating, in, different, developmental, windows])]). relacion([sujeto(['The', presence, 'and/or', elevated, expression, of, elements]), verbo([associated]), complemento([with, an, ongoing, establishment, of, a, 'T', cell, signature, in, the, most, primitive, fetal, subset, is, highly, suggestive, for, an, extrathymic, initiation, of, 'T', cell, specification, and, underlines, the, fundamental, differences, in, fetal, versus, adult, lymphopoiesis])]). relacion([sujeto(['T-box']), verbo([expressed]), complemento([in, 'T', cells, '(', 'T-bet)', is, an, essential, transcription, factor, for, 'T', helper, '(', 'Th)', cell, differentiation, and, function])]). relacion([sujeto(['T-bet', mRNA, expression, in, 'CD4+', 'T', cells, from, 'AHB', patients, was]), verbo([enhanced]), complemento([compared, with, 'CHB', patients, and, healthy, controls])]). relacion([sujeto(['In', 'conclusion,', lentivirally, overexpressed, 'T-bet']), verbo([regulates]), complemento(['Th', cell, lineage, commitment, in, 'CHB', 'patients,', which, may, be, mediated, by, regulating, 'HLX1,', 'GATA-3', and, 'STAT-6', expression])]). relacion([sujeto(['The', development, of, 'T', cells, from, multipotent, progenitors, in, the, thymus, occurs, by, cascades, of, interactions, between, signaling, molecules, and, transcription, 'factors,', resulting, in, the]), verbo([loss]), complemento([of, alternative, lineage, potential, and, the, acquisition, of, the, 'T-cell', functional, identity])]). relacion([sujeto(['These', processes]), verbo([require]), complemento(['Notch', signaling, and, the, activity, of, 'GATA3,', 'TCF1,', 'Bcl11b,', and, the, 'E-proteins', 'HEB', and, 'E2A'])]). relacion([sujeto(['We']), verbo([have]), complemento([shown, that, 'HEB', factors, are, required, to, inhibit, the, thymic, 'NK', cell, fate, and, that, 'HEBAlt', allows, the, passage, of, 'T-cell', precursors, from, the, 'DN', to, 'DP', stage, but, is, insufficient, for, suppression, of, the, 'NK', cell, lineage, choice])]). relacion([sujeto(['HEB', factors, are, also]), verbo([required]), complemento([to, enforce, the, death, of, cells, that, have, not, rearranged, their, 'TCR', genes])]). relacion([sujeto(['Most', studies, about, functions, of, aryl, hydrocarbon, receptor, '(', 'AhR)', in, the, pathogenesis, of, asthma]), verbo([have]), complemento([been, carried, out, with, 'non-physiological', industrial, 'by-products', such, as, 2, ',', 3, ',', 7, ',', 8, -, 'tetrachlorodibenzo-p-dioxin', and, 'benzo(a)pyrene'])]). relacion([sujeto(['Flow', cytometric, analysis, of, mediastinal, lymph, nodes, showed, that, 'IL-4', producing, cells]), verbo([decreased]), complemento([in, 'FICZ-treated', mice, compared, with, 'PBS', control])]). relacion([sujeto(['FICZ']), verbo([inhibited]), complemento([both, 'Th2', differentiation, and, the, expression, of, 'GATA-3'])]). relacion([sujeto(['Finally,', activation, of, 'STAT6,', which, is, necessary, for, 'Th2', 'differentiation,', was]), verbo([inhibited]), complemento([by, 'FICZ'])]). relacion([sujeto(['Aberrant', transcriptional, activities]), verbo([have]), complemento([been, documented, in, breast, cancers])]). relacion([sujeto(['Studies', often]), verbo([find]), complemento([some, transcription, factors, to, be, inappropriately, regulated, and, enriched, in, certain, pathological, states])]). relacion([sujeto(['The', promoter, regions, of, most]), verbo([target]), complemento([genes, have, binding, sites, for, their, transcription, factors])]). relacion([sujeto(['An', ample, of, evidence, supports, their, combinatorial, effect, on, their, shared]), verbo([target]), complemento([gene, expressions])]). relacion([sujeto(['Here,', we, used, a, new, statistic, 'method,', bivariate, 'CID,', to, predict, combinatorial, interaction, activity, between, 'ERα', and, a, transcription, factor, '(', 'E2F1or', 'GATA3', or, 'ERRα)', in]), verbo([regulating]), complemento([target, gene, expression, via, four, regulatory, mechanisms])]). relacion([sujeto(['Bivariate', network, analysis, revealed, several]), verbo([target]), complemento([genes, previously, implicated, in, tumor, angiogenesis, are, among, the, predicted, shared, 'targets,', including, 'VEGFA,', 'PDGFRB'])]). relacion([sujeto(['In', 'summary,', our, analysis]), verbo([suggests]), complemento([the, importance, for, the, multivariate, space, of, an, inferred, 'ERα', transcriptional, regulatory, network, in, breast, cancer, diagnostic, and, therapeutic, development])]). relacion([sujeto(['Chrysin,', a, flavonoid, obtained, from, various, natural, 'sources,']), verbo([has]), complemento([been, reported, to, possess, 'anti-inflammatory,', 'antitumor,', antioxidant, and, 'anti-allergic', activities])]). relacion([sujeto(['In', the, present, 'study,', we, examined, the, effects, of, chrysin, on, airway, inflammation, and, the, possible, mechanisms, through, which, it]), verbo([acts]), complemento([in, a, murine, model, of, allergic, asthma])]). relacion([sujeto(['Chrysin', significantly]), verbo([suppressed]), complemento(['OVA-induced', airway, hyperresponsiveness, '(', 'AHR)', to, acetylcholine, chloride, '(', 'Ach)'])]). relacion([sujeto(['Chrysin', administration, significantly]), verbo([inhibited]), complemento([the, total, inflammatory, cell, and, eosinophil, counts, in, bronchoalveolar, lavage, fluid, '(', 'BALF)', and, total, immunoglobulin, 'E', '(', 'IgE)', levels, in, serum])]). relacion([sujeto(['In', 'addition,', chrysin]), verbo([triggered]), complemento([a, switch, of, the, immune, response, to, allergens, towards, a, 'T-helper', type, 1, '(', 'Th1)', profile, by, modulating, the, transcription, factors, 'T-bet', and, 'GATA-3', in, allergic, mice])]). relacion([sujeto(['These', data]), verbo([suggest]), complemento([that, chrysin, exhibits, 'anti-inflammatory', and, immunoregulatory, properties, and, provides, new, insights, into, the, immunopharmacological, role, of, chrysin, in, terms, of, its, effects, in, a, murine, model, of, asthma])]). relacion([sujeto(['LCs', are]), verbo([associated]), complemento([with, epidermal, nerves, and, the, neuropeptides, vasoactive, intestinal, polypeptide, '(', 'VIP)', and, pituitary, adenylate, 'cyclase-activating', polypeptide, '(', 'PACAP)', inhibit, 'LC', 'Ag', presentation, for, 'Th1-type', immune, responses])]). relacion([sujeto(['Here,', we, examined, whether, 'PACAP', or, 'VIP']), verbo([modulates]), complemento(['LC', 'Ag', presentation, for, induction, of, 'IL-17A-producing', 'CD4(+)', 'T', cells])]). relacion([sujeto(['Treatment', with, 'VIP', or, 'PACAP', prior, to, in, vitro, 'LC', 'Ag', presentation, to, 'CD4(+)', 'T', cells]), verbo([enhanced]), complemento(['IL-17A,', 'IL-6,', and, 'IL-4', 'production,', decreased, interferon, '(', 'IFN)-γ', and, interleukin, '(', 'IL)-22', 'release,', and, increased, 'RORγt', and, 'Gata3', mRNA, expression, while, decreasing, 'T-bet', expression])]). relacion([sujeto(['The', 'CD4(+)', 'T-cell', population, was]), verbo([increased]), complemento([in, 'IL-17A-', and, 'IL-4-expressing', cells, and, decreased, in, 'IFN-γ-expressing', cells])]). relacion([sujeto(['Addition', of, 'anti-IL-6', mAb, blocked, the]), verbo([enhanced]), complemento(['IL-17A', production, seen, with, 'LC', preexposure, to, 'VIP', or, 'PACAP'])]). relacion([sujeto(['Intradermal', administration, of, 'VIP', or, 'PACAP', prior, to, application, of, a, contact, sensitizer, at, the, injection, 'site,', followed, by, harvesting, of, draining, lymph, node, 'CD4(+)', 'T', cells, and, stimulation, with, 'anti-CD3/anti-CD28', 'mAbs,']), verbo([enhanced]), complemento(['IL-17A', and, 'IL-4', production, but, reduced, production, of, 'IL-22', and, 'IFN-γ'])]). relacion([sujeto(['PACAP', and, 'VIP', are, endogenous, mediators, that, likely]), verbo([regulate]), complemento([immunity, and, 'immune-mediated', diseases, within, the, skin])]). relacion([sujeto(['However,', 'TEAD4', is]), verbo([expressed]), complemento([in, the, 'TE', and, the, 'ICM'])]). relacion([sujeto(['Thus,', differential, function, of, 'TEAD4', rather, than, expression, itself]), verbo([regulates]), complemento([specification, of, the, first, two, cell, lineages])]). relacion([sujeto(['We', used, 'ChIP', sequencing, to, define, genomewide, 'TEAD4']), verbo([target]), complemento([genes, and, asked, how, transcription, of, 'TEAD4', target, genes, is, specifically, maintained, in, the, 'TE'])]). relacion([sujeto(['Our', analyses, revealed, an, evolutionarily]), verbo([conserved]), complemento(['mechanism,', in, which, lack, of, nuclear, localization, of, 'TEAD4', impairs, the, 'TE-specific', transcriptional, program, in, inner, 'blastomeres,', thereby, allowing, their, maturation, toward, the, 'ICM', lineage])]). relacion([sujeto(['Restoration', of, 'TEAD4']), verbo([nuclear]), complemento([localization, maintains, the, 'TE-specific', transcriptional, program, in, the, inner, blastomeres, and, prevents, segregation, of, the, 'TE', and, 'ICM', lineages, and, blastocyst, formation])]). relacion([sujeto(['Puumala', hantavirus, '(', 'PUUV)', 'infection,', also, known, as, nephropathia, 'epidemica,', is, the, most, common]), verbo([cause]), complemento([of, hemorrhagic, fever, with, renal, syndrome, '(', 'HFRS)', in, 'Europe'])]). relacion([sujeto(['Maximum', plasma, interleukin, '(', 'IL)-6,', urine, 'IL-6,', and, urine, 'IL-8', concentrations, were, positively]), verbo([associated]), complemento([with, 'PUUV-induced', 'AKI'])]). relacion([sujeto(['By', multivariate, 'analyses,', we]), verbo([found]), complemento([that, the, maximum, levels, of, leukocytes, and, urinary, sediment, 'GATA-3', mRNA, during, acute, illness, were, independent, risk, factors, for, severe, 'PUUV-induced', 'AKI'])]). relacion([sujeto(['We']), verbo([have]), complemento([identified, novel, acute, illness, risk, factors, for, severe, 'PUUV-induced', 'AKI'])]). relacion([sujeto(['Allergic', asthma, is, a, common, inflammatory, disease]), verbo([regulated]), complemento([by, the, 'T', helper, '(', 'Th)', cells])]). relacion([sujeto(['This', study, investigated, whether, 'IRF4', is]), verbo([involved]), complemento([in, the, systemic, immune, responses, in, allergic, asthma, patients])]). relacion([sujeto(['The', levels, of, 'GATA']), verbo([binding]), complemento([protein, 3, '(', 'GATA3),', retinoic, 'acid-related', orphan, receptor, γt, '(', 'RORγt),', and, forkhead, box, 'P3', '(', 'FOXP3),', the, master, transcription, factors, controlling, 'Th2,', 'Th17,', and, 'T', regulatory, cells, 'differentiation,', 'respectively,', were, examined, by, quantitative, 'RT-PCR'])]). relacion([sujeto(['Our', results]), verbo([suggested]), complemento([that, 'IRF4', may, play, a, role, in, the, systemic, inflammation, of, allergic, asthma, patients, by, facilitating, the, differentiation, of, 'Th2', and, 'Th17', cells, at, least, at, the, transcriptional, level])]). relacion([sujeto(['The', downstream, of, kinase, '(', 'DOK)-1', is]), verbo([involved]), complemento([in, the, protein, tyrosine, kinase, '(', 'PTK)', pathway, in, mast, 'cells,', but, the, role, of, 'DOK-1', in, the, pathogenesis, of, asthma, has, not, been, defined])]). relacion([sujeto(['In', this, 'study,', we]), verbo([have]), complemento([demonstrated, a, novel, regulatory, role, of, 'DOK-1', in, airway, inflammation, and, physiologic, responses, in, a, murine, model, of, asthma, using, lentiviral, vector, containing, 'DOK-1', cDNA, or, 'DOK-1-specific', 'ShRNA'])]). relacion([sujeto(['The', transgenic, introduction, of, 'DOK-1', significantly]), verbo([stimulated]), complemento([the, activation, and, expression, of, 'STAT-4', and, 'T-bet,', while, impressively, inhibiting, the, activation, and, expression, of, 'STAT-6', and, 'GATA-3', in, airway, epithelial, cells])]). relacion([sujeto(['On', the, other, 'hand,', 'DOK-1', knockdown, mice]), verbo([enhanced]), complemento(['STAT-6', expression, and, its, nuclear, translocation, compared, to, 'OVA-challenged', control, mice])]). relacion([sujeto(['When', viewed, in, 'combination,', our, studies, demonstrate, 'DOK-1']), verbo([regulates]), complemento(['allergen-induced', 'Th2', immune, responses, by, selective, stimulation, and, inhibition, of, 'STAT-4', and, 'STAT-6', signaling, 'pathways,', respectively])]). relacion([sujeto(['These', studies]), verbo([provide]), complemento([a, novel, insight, on, the, regulatory, role, of, 'DOK-1', in, 'allergen-induced', 'Th2', inflammation, and, airway, 'responses,', which, has, therapeutic, potential, for, asthma, and, other, allergic, diseases])]). relacion([sujeto(['Transplant', glomerulopathy, is, an, important]), verbo([cause]), complemento([of, late, graft, loss])]). relacion([sujeto(['Here', we, measured, the, expression, of, 'T-bet', '(', a, member, of, the, 'T-box', family, of, transcription, factors]), verbo([regulating]), complemento(['Th1', lineage, 'commitment)', and, its, relationship, with, inflammation, in, 70, patients, with, transplant, glomerulopathy])]). relacion([sujeto(['There', was, a, significant]), verbo([increase]), complemento([in, 'T-bet', expression, in, both, glomerular, and, peritubular, capillaries, of, the, transplant, glomerulopathy, group])]). relacion([sujeto(['The', expression, of, 'GATA3,', a, 'Th2', 'regulator,', was, rarely]), verbo([found]), complemento([in, the, transplant, glomerulopathy, group])]). relacion([sujeto(['Transplant', glomerulopathy, was]), verbo([associated]), complemento([with, diffuse, peritubular, capillary, dilation, without, reduced, capillary, density])]). relacion([sujeto(['Since', endothelial, injury, is, a, typical, lesion, that, follows, alloantibody, 'reactivity,', our, results]), verbo([suggest]), complemento([that, 'T-bet', is, involved, in, the, pathogenesis, of, this, glomerulopathy])]). relacion([sujeto(['Mounting', evidence, from, animal, models]), verbo([has]), complemento([demonstrated, that, alterations, in, 'peptide-MHC', interactions, with, the, 'T', cell, receptor, '(', 'TCR)', can, lead, to, dramatically, different, 'T', cell, outcomes])]). relacion([sujeto(['We']), verbo([have]), complemento([developed, an, altered, peptide, ligand, of, type, 'II', 'collagen,', referred, to, as, 'A9,', which, differentially, regulates, 'TCR', signaling, in, murine, 'T', cells, leading, to, suppression, of, arthritis, in, the, experimental, model, of, 'collagen-induced', arthritis])]). relacion([sujeto(['This', study, delineates, the, 'T', cell, signaling, pathway, used, by, 'T', cells]), verbo([stimulated]), complemento([by, the, 'A9·I-A(q)', complex])]). relacion([sujeto(['We']), verbo([have]), complemento([found, that, 'T', cells, activated, by, 'A9', bypass, the, requirement, for, 'Zap-70', and, 'CD3-ζ', and, signal, via, 'FcRγ', and, 'Syk'])]). relacion([sujeto(['Using', 'collagen-specific', 'T', cell, hybridomas, engineered, to, overexpress, either, 'Syk,', 'Zap-70,', 'TCR-FcRγ,', or, 'CD3-ζ,', we, demonstrate, that, 'A9·I-A(q)', preferentially]), verbo([activates]), complemento(['FcRγ/Syk', but, not, 'CD3-ζ/Zap-70'])]). relacion([sujeto(['Moreover,', a, genetic, absence, of, 'Syk', or, 'FcRγ', significantly, reduces, the, altered, peptide, ligand, induction, of, the]), verbo([nuclear]), complemento([factor, 'GATA3'])]). relacion([sujeto(['By', dissecting, the, molecular, mechanism, of, 'A9-induced', 'T', cell, signaling, we]), verbo([have]), complemento([defined, a, new, alternate, pathway, that, is, dependent, upon, 'FcRγ', and, 'Syk', to, secrete, immunoregulatory, cytokines])]). relacion([sujeto(['Hence,', the, -, 237, polymorphic, site, in, the, 5, '\'', promoter, region, of, the, 'IL-12Rβ2', '(', 'SNP', 'ID:', 'rs11810249)', gene]), verbo([associated]), complemento([with, the, 'AP-4', transcription, motif, 'GAGCTG,', was, examined])]). relacion([sujeto(['Similarly,', densitometric, analysis, of, the, 'EMSA', assay, showed, reduced]), verbo([binding]), complemento([of, the, 'AP-4', transcription, 'factor,', to, 'T', compared, to, the, 'C', nucleotide, probe])]). relacion([sujeto(['Notwithstanding', the, presence, of, high, levels, of, 'IL-12Rβ2', mRNA, in, these, patients, elevated, 'IFN-α', expression, could]), verbo([modulate]), complemento([their, immune, responses, to, 'Mycobacterium', tuberculosis])]). relacion([sujeto(['Genistein,', a, flavonoid, in, legumes, and, some, herbal, 'medicines,']), verbo([has]), complemento([various, biological, actions])]). relacion([sujeto(['Previous', studies]), verbo([have]), complemento([shown, that, genistein, decreased, airway, inflammation, in, allergic, asthma])]). relacion([sujeto(['The', mRNA, expression, of, 'GATA']), verbo([binding]), complemento([protein, 3, '(', 'GATA-3),', signal, transducer, and, activator, of, transcription, 6, '(', 'STAT-6)', and, 'T-box', transcription, factor, '(', 'T-bet)', in, the, lungs, and, 'CD4+', 'T', cells, of, each, group, were, detected, by, 'real-time', 'PCR', and, the, corresponding, proteins, were, detected, by, 'Western', blot])]). relacion([sujeto(['The', results, showed, that, genistein, attenuated, 'OVA-induced', airway, 'inflammation,']), verbo([decreased]), complemento(['Th2-type', cytokines, and, increased, 'Th1-type', cytokines])]). relacion([sujeto(['Additionally,', our, data]), verbo([suggested]), complemento([that, genistein, may, modulate, the, 'Th1/Th2', reaction, by, inhibiting, 'GATA-3', and, 'STAT-6', production, while, increasing, 'T-bet', production])]). relacion([sujeto(['Genistein', may]), verbo([modulate]), complemento([the, immunomodulatory, actions, caused, by, 'Th1/Th2', cytokines, in, 'asthma,', at, least, 'partially,', by, the, 'down-regulation', of, 'GATA-3', and, 'STAT-6', and, the, 'up-regulation', of, 'T-bet'])]). relacion([sujeto(['To', define, molecular, mechanisms, controlling, this, 'progression,', we, probed, five, stages, spanning, the, commitment, process, using, 'RNA-seq', and, 'ChIP-seq', to, track, 'genome-wide', shifts, in, 'transcription,', cohorts, of, active, transcription, factor, 'genes,', histone, modifications, at, diverse, classes, of, 'cis-regulatory', 'elements,', and]), verbo([binding]), complemento([repertoire, of, 'GATA-3', and, 'PU'])]). relacion([sujeto(['The', results, highlight, potential, 'promoter-distal', 'cis-regulatory', elements, in, play, and]), verbo([reveal]), complemento([both, activation, sites, and, diverse, mechanisms, of, repression, that, silence, genes, used, in, alternative, lineages])]). relacion([sujeto(['In vivo']), verbo([binding]), complemento([of, 'PU'])]). relacion([sujeto([1, and, 'GATA-3', relative, to, epigenetic, marking]), verbo([reveals]), complemento([distinctive, 'factor-specific', 'rules for', recruitment, of, these, crucial, transcription, factors, to, different, subsets, of, their, potential, 'sites,', dependent, on, dose, and, developmental, context])]). relacion([sujeto(['Compound', 'A', '(', 'CpdA)', is, a, dissociating, 'non-steroidal', glucocorticoid, receptor, '(', 'GR)', ligand, which]), verbo([has]), complemento(['anti-inflammatory', properties, exerted, by, 'down-modulating', proinflammatory, gene, expression])]). relacion([sujeto(['By', favouring, 'GR', monomer, 'formation,', 'CpdA', does, not]), verbo([enhance]), complemento([glucocorticoid, '(', 'GC)', response, 'element-driven', gene, 'expression,', resulting, in, a, reduced, side, effect, profile, as, compared, to, 'GCs'])]). relacion([sujeto(['Considering', the, importance, of, 'Th1/Th2', balance, in, the, final, outcome, of, immune, and, inflammatory, 'responses,', we, analyzed, how, selective, 'GR', modulation, differentially]), verbo([regulates]), complemento([the, activity, of, 'T-bet', and, 'GATA-3,', master, drivers, of, 'Th1', and, 'Th2', 'differentiation,', respectively])]). relacion([sujeto(['Using', 'Western', analysis, and, reporter, gene, 'assays,', we, show, in, murine, 'T', cells, 'that,', similar, to, 'GCs,', 'CpdA']), verbo([inhibits]), complemento(['T-bet', activity, via, a, transrepressive, mechanism])]). relacion([sujeto(['Different', from, 'GCs,', 'CpdA']), verbo([induces]), complemento(['GATA-3', activity, by, p38, 'MAPK-induction', of, 'GATA-3', phosphorylation, and, nuclear, translocation])]). relacion([sujeto(['ELISA', assays, demonstrate, that, modulation, of, 'T-bet', and, 'GATA-3', impacts, on, cytokine, production, shown, by, a]), verbo([decrease]), complemento([in, 'IFN-γ', and, an, increase, in, 'IL-5', 'production,', respectively])]). relacion([sujeto(['Erythropoietin']), verbo([acts]), complemento([by, binding, to, its, cell, surface, receptor, on, erythroid, progenitor, cells, to, stimulate, erythrocyte, production])]). relacion([sujeto(['Mice', with, erythropoietin, receptor, restricted, to, hematopoietic, tissue, were, used, to, assess, contributions, of, endogenous, erythropoietin, to]), verbo([promote]), complemento([skeletal, myoblast, proliferation, and, survival, and, wound, healing, in, a, mouse, model, of, cardiotoxin, induced, muscle, injury])]). relacion([sujeto(['In', 'contrast,', mice, with, chronic, elevated, circulating, erythropoietin, had, more, 'Pax-7(+)', satellite, cells, and, myoblasts, with]), verbo([increased]), complemento([proliferation, and, survival, in, 'culture,', decreased, muscle, 'injury,', and, accelerated, recovery, of, maximum, load, tolerated, by, isolated, muscle])]). relacion([sujeto(['Skeletal', muscle, myoblasts, also, produced, endogenous, erythropoietin, that]), verbo([increased]), complemento([at, low, 'O(2)'])]). relacion([sujeto(['Erythropoietin']), verbo([promoted]), complemento(['proliferation,', 'survival,', and, wound, recovery, in, myoblasts, via, the, phosphoinositide, 3, -, 'kinase/AKT', pathway])]). relacion([sujeto(['Therefore,', endogenous, and, exogenous, erythropoietin, contribute, to]), verbo([increasing]), complemento([satellite, cell, number, following, muscle, 'injury,', improve, myoblast, proliferation, and, 'survival,', and, promote, repair, and, regeneration, in, this, mouse, induced, muscle, injury, model, independent, of, its, effect, on, erythrocyte, production])]). relacion([sujeto(['Higher', gene, expression, levels, of, 'IL-17A', and, 'IFN-γ', were, significantly]), verbo([associated]), complemento([with, remission, after, three, 'IFX', infusions, '(', 'OR', =, 5.4, ',', p, =, 0.013, and, 'OR', =, 5.5, ',', p, =, 0.011, ',', 'respectively)'])]). relacion([sujeto(['Th2', and, 'Treg-related', mediators, were, not, significantly]), verbo([associated]), complemento([with, clinical, 'outcome,', but, were, expressed, at, higher, levels, in, 'UC', patients, compared, with, the, controls])]). relacion([sujeto(['Immunohistochemistry', '(', 'IHC)', confirmed, the, presence, of, cells]), verbo([expressing]), complemento([both, 'IL-17A', and, 'IFN-γ'])]). relacion([sujeto(['This', proliferation, depends, upon, appropriate, cues, from, the, 'antigen-presenting', cells, that]), verbo([have]), complemento([processed, the, antigen, and, present, the, peptide, to, the, 'T', 'cells,', and, requires, the, establishment, of, a, cytokine, environment, that, can, support, such, proliferation])]). relacion([sujeto(['Expansion', of, 'antigen-specific', 'CD4(+)', 'T', cells, needs, to, be, coupled, with, differentiation, into, one, of, several, 'effector/regulatory', phenotypes, if, the, priming, event, is, to, result, in, cells, that, can, initially]), verbo([act]), complemento([to, control, the, particular, pathogen, that, elicited, the, 'response,', and, later, to, serve, as, memory, cells, to, insure, an, appropriate, response, upon, reintroduction, of, the, pathogen])]). relacion([sujeto(['Here,', we, discuss, the, initiation, of, 'T', helper, lineage, 'commitment,', the, positive, feedback, regulation, by, the, cytokine, environment, to]), verbo([enhance]), complemento([and, stabilize, the, differentiation, into, distinct, 'T', helper, 'subsets,', and, the, biological, significance, of, 'CD4(+)', 'T', cell, plasticity, and, 'long-term', 'CD4(+)', 'T', cell, memory])]). relacion([sujeto(['Ulcerative', colitis, '(', 'UC)', and, 'Crohn\'s', disease, '(', 'CD)']), verbo([have]), complemento([unique, as, well, as, overlapping, 'phenotypes,', susceptibility, 'genes,', and, gene, expression, profiles])]). relacion([sujeto(['Expression', levels, of, signaling, molecules, including, 'IL-6/10/12/13/17/23/33,', 'STAT1/3/6,', 'T-bet,', 'GATA3,', 'Foxp3,', 'SOCS1/3,', and, downstream, inflammatory, mediators, such, as, chemokines, 'CCL-2/11/17/20,', oxidative, stress, 'inducers,', 'proteases,', and, mucosal, genes, were, differentially]), verbo([regulated]), complemento([between, 'UC', and, 'CD', and, between, active, and, quiescent, disease])]). relacion([sujeto(['This', comprehensive, approach, to, quantifying, gene, expression]), verbo([provides]), complemento([insights, into, the, pathogenesis, of, 'IBD', by, elucidating, distinct, immune, signaling, networks, in, 'CD', and, 'UC'])]). relacion([sujeto(['FOXP3(+)', 'T-reg', were]), verbo([increased]), complemento([in, 'GC-naïve', 'NP,', and, numbers, were, negatively, correlated, with, eosinophil, infiltration])]). relacion([sujeto(['Helios', staining, was, not, 'detected,']), verbo([suggesting]), complemento([that, 'FOXP3(+)', cells, in, 'NP', are, not, 'thymus-derived', 'T-reg'])]). relacion([sujeto(['Compared', with, 'controls,', mRNA, levels, corresponding, to, 'T-reg', genes, were, significantly]), verbo([increased]), complemento([in, 'NP', '(', 'FOXP3,', 'TGFB1,', 'IL10,', 'SMAD3,', 'IL2RA,', and, 'JAK3),', but, transcription, factors, associated, with, 'Th2', '(', 'GATA3)', or, 'Th17', responses, '(', 'RORc)', were, significantly, reduced])]). relacion([sujeto(['GC', therapy, significantly]), verbo([suppressed]), complemento([eosinophilic, inflammation, in, 'NP,', but, did, not, significantly, alter, the, expression, levels, of, 'T-reg/Th2-associated', genes])]). relacion([sujeto(['Expression', of, 'T-reg/Th2', markers, after, 'GC', treatment, was, 'unaltered,']), verbo([suggesting]), complemento([that, 'T-cell-driving', 'NP', inflammatory, mediators, are, 'GC', resistant])]). relacion([sujeto(['The', 6, -, sulfation, process, is]), verbo([mediated]), complemento([by, 6, -, sulfotransferase, family, isoenzymes])]). relacion([sujeto(['We', previously, demonstrated, that, 'GlcNAc6ST-1,', one, of, the, isoenzyme, 'genes,', is]), verbo([induced]), complemento([by, 'GATA-3', and, 'NF-κB', in, human, helper, 'T', '(', 'Th)', cells])]). relacion([sujeto([5, '\'', -, 'RACE', 'analysis,', chromatin, 'immunoprecipitation,', and, reporter, assays, were, performed, to]), verbo([reveal]), complemento([transcriptional, regulation, of, 'HEC-GlcNAc6ST'])]). relacion([sujeto(['We', identified, potential]), verbo([binding]), complemento([sites, of, 'Sp1,', 'T-bet,', and, 'GATA-3', in, the, 'HEC-GlcNAc6ST', promoter])]). relacion([sujeto(['Reporter', assays, indicated, that, transfection, of, 'Sp1']), verbo([enhanced]), complemento([the, 'activity,', whereas, mithramycin, 'A,', an, 'Sp1-specific', 'inhibitor,', repressed, it])]). relacion([sujeto(['Transfection', of, 'T-bet']), verbo([increased]), complemento([the, 'activity,', which, was, inhibited, by, introducing, a, mutation, into, the, potential, 'T-bet', binding, site])]). relacion([sujeto(['GATA-3', alone, could, not, elevate, the, 'activity,', although, 'co-transfection', of, protein, kinase, 'A,', which, is, known, to]), verbo([enhance]), complemento(['IL-5', transcription, in, 'Th2', cells, through, phosphorylation, of, 'GATA-3,', caused, elevation])]). relacion([sujeto(['From', these, 'results,', we, concluded, that, 'T-bet', and, 'GATA-3', as, well, as, 'Sp1', control, the, expression, of, glycan, with, 'cell-adhesion', activity, by]), verbo([regulating]), complemento(['HEC-GlcNAc6ST', transcription, in, 'Th', cells])]). relacion([sujeto(['These', results, may]), verbo([provide]), complemento([a, clue, to, biological, regulation, of, 'Th-cell', interaction, with, selectins, and, other, 'carbohydrate-recognition', molecules, by, 'T-bet', and, 'GATA-3'])]). relacion([sujeto(['Obviously,', 'type-2', cytokines, '(', 'IL-4,', 'IL-5,', 'IL-9,', 'IL-13)', and, particularly, 'IL-4']), verbo([have]), complemento([been, identified, as, potential, targets, for, allergy, treatment])]). relacion([sujeto(['While', initial, experiences, using, 'anti-IL-4', principles, in, asthma, were, rather, 'ambiguous,', more, recent, studies, using, an, 'IL-4', mute, in, blocking, the, 'IL-4', and, 'IL-13', receptor]), verbo([have]), complemento([shown, promising, results])]). relacion([sujeto(['Furthermore,', our, understanding, of, 'IL-4', biology, is, more, specific, and, may]), verbo([promote]), complemento([more, targeted, interventions])]). relacion([sujeto(['A', key, function, of, 'IL-4', is, the, induction, of, '\'', master, 'switch\'', transcription, factor, 'GATA3', that, drives, 'Th2', differentiation, and, also, effectively]), verbo([inhibits]), complemento([the, induction, of, regulatory, 'T', cells])]). relacion([sujeto(['However,', like, other, 'oligonucleotide-based', molecules, these, substances, might, exert, 'so-called', 'off-target', 'effects,', which]), verbo([have]), complemento([not, been, investigated, so, far, for, this, molecule, class])]). relacion([sujeto(['Therefore,', the, present, study, investigates, putative, 'off-target', effects, of, 'DNAzymes', on, innate, immune, mechanisms, using, 'GATA-3-specific', 'DNAzymes', that]), verbo([have]), complemento([recently, been, developed, as, novel, therapeutic, approach, for, the, treatment, of, allergic, diseases, including, allergic, asthma])]). relacion([sujeto(['The']), verbo([conserved]), complemento([catalytic, domain, of, 10, -, 23, 'DNAzymes', contains, a, 'CpG', motif, that, may, stimulate, innate, immune, cells, via, 'Toll-like', receptor, 9, '(', 'TLR-9)'])]). relacion([sujeto(['T', cell, 'Ig', and, 'ITIM', domain, '(', 'TIGIT)', is, a, newly, identified, receptor]), verbo([expressed]), complemento([on, 'T', cells, that, binds, to, 'CD155', on, the, dendritic, cell, 'surface,', driving, them, to, a, more, tolerogenic, phenotype])]). relacion([sujeto(['Using', an, agonistic, 'anti-TIGIT', 'mAb,', we, demonstrate, a, direct, inhibitory, effect, on, 'T', cell, proliferation, with, a]), verbo([decrease]), complemento([in, expression, of, 'T-bet,', 'GATA3,', 'IFN', regulatory, factor, 4, ',', and, retinoic, 'acid-related', orphan, receptor, c, with, inhibition, of, cytokine, 'production,', predominantly, 'IFN-γ'])]). relacion([sujeto(['Knockdown', of, 'TIGIT', expression, by, short, hairpin, 'RNA', resulted, in, an]), verbo([increase]), complemento([of, both, 'T-bet', and, 'IFN-γ', mRNA, and, protein, expression, with, concomitant, decrease, in, 'IL-10', expression])]). relacion([sujeto(['These', data, demonstrate, that, 'TIGIT', can]), verbo([inhibit]), complemento(['T', cell, functions, by, competing, with, 'CD226', and, can, also, directly, inhibit, 'T', cells, in, a, 'T', 'cell-intrinsic', manner])]). relacion([sujeto(['Our', results]), verbo([provide]), complemento([evidence, for, a, novel, role, of, this, alternative, costimulatory, pathway, in, regulating, human, 'T', cell, responses, associated, with, autoimmune, disease])]). relacion([sujeto([20, '(', 'R)-Rg3']), verbo([promoted]), complemento([significantly, higher, 'serum-specific', 'IgG', and, the, 'IgG', isotype, responses, in, association, with, highly, 'up-regulated', serum, 'IFN-γ', and, 'IL-5', than, 20, '(', 'S)-Rg3'])]). relacion([sujeto(['In', 'addition,', 20, '(', 'R)-Rg3', significantly]), verbo([enhanced]), complemento([splenocyte, proliferative, responses, to, 'Con', 'A,', 'LPS', and, 'OVA', as, well, as, mRNA, expression, of, 'IFN-γ,', 'IL-12,', 'IL-4', and, 'IL-10', and, transcription, factors, 'T-bet', and, 'GATA-3', by, splenocytes, when, compared, with, the, 20, '(', 'S)-Rg3'])]). relacion([sujeto(['Therefore,', ginsenoside, 'Rg3', is, stereospecific, in, stimulation, of, the, immune, 'response,', and, 20, '(', 'R)-Rg3']), verbo([has]), complemento([more, potent, adjuvant, activity, than, 20, '(', 'S)-Rg3'])]). relacion([sujeto(['Here,', we]), verbo([have]), complemento([demonstrated, that, in, addition, to, regulating, the, onset, of, this, 'transition,', 'HEB', and, 'E2A', also, play, a, separate, role, in, 'CD4(+)', lineage, choice])]). relacion([sujeto(['Depending', on, polarizing, cytokine, signals, during, activation, by, 'antigen,', naïve, 'CD4+', 'T', cells, can, be]), verbo([stimulated]), complemento([and, differentiated, into, distinct, functional, 'CD4+', 'T', cell, subsets, such, as, 'Th1,', 'Th2', and, 'Tr1', cells])]). relacion([sujeto(['The', overlapping, expression, of, some, signature, cytokines, by, 'Th2', and, other, subsets, of, 'CD4+', 'T', cells, may, not, only, indicate, the, plasticity, of, 'CD4+', 'T', 'cells,', but, could, also]), verbo([suggest]), complemento([the, possibility, of, the, deletion, of, a, single, signature, cytokine, gene, leading, to, the, functional, differentiation, of, naïve, 'CD4+', 'T', cells, into, effector, 'Th1', or, 'Tr1', cells, under, 'Th2', differentiation, conditions])]). relacion([sujeto(['In', this, 'work,', we]), verbo([stimulated]), complemento([naïve, 'CD4+', 'T', cells, derived, from, 'OT', 'II', mice, or, 'OT', 'II', mice, that, were, deficient, in, individual, cytokines, '(', 'IL-4,', 'IL-5,', 'IL-6', and, 'IL-10)', with, 'OVA-pulsed', dendritic, cells, '(', 'DC(OVA))', in, the, presence, of, 'IL-4', and, 'anti-IFN-γ,', to, generate, 'OVA-specific', 'wild-type', '(', 'WT)', 'Th2,', and, 'Th2(IL-4', 'KO),', or, 'Th2(IL-5', 'KO),', or, 'Th2(IL-6', 'KO),', or, 'Th2(IL-10', 'KO)', 'cells,', and, to, assess, their, capacity, in, modulating, 'DC(OVA)-induced', 'CD8+', cytotoxic, 'T', lymphocyte, '(', 'CTL)', 'responses,', and, antitumor, immunity, in, 'WT', 'C57BL/6', mice])]). relacion([sujeto(['We', conclusively, demonstrate, that, 'GATA-3-expressing', 'Th2', cells]), verbo([enhance]), complemento(['DC(OVA)-induced', 'CTL', responses, via, 'IL-6', secretion])]). relacion([sujeto(['We', also, show, that, 'IL-6', and, 'IL-10', gene, deficient, 'Th2(IL-6', 'KO)', and, 'Th2(IL-10', 'KO)', 'cells,', but, not, 'IL-4', and, 'IL-5', gene, deficient, 'Th2(IL-4', 'KO)', and, 'Th2(IL-5', 'KO)', 'cells,', behave, like, functional, 'Tr1', and, 'Th1', cells, by]), verbo([inhibiting]), complemento([and, enhancing, 'DC(OVA)-induced', 'OVA-specific', 'CD8+', 'CTL', responses, and, antitumor, 'immunity,', respectively])]). relacion([sujeto(['We', further, elucidate, that, inhibition, and, enhancement, of, 'DC(OVA)-induced', 'OVA-specific', 'CTL', responses, by, 'Th2(IL-6', 'KO)', and, 'Th2(IL-10', 'KO)', cells, are]), verbo([mediated]), complemento([by, their, immune, suppressive, 'IL-10', and, 'pro-inflammatory', 'IL-6', 'secretion,', respectively])]). relacion([sujeto(['Taken', 'together,', our, study]), verbo([suggests]), complemento([that, deletion, of, a, single, cytokine, gene, 'IL-6', and, 'IL-10', makes, 'CD4+', 'Th2', cells, become, effector, 'CD4+', 'Tr1-', and, 'Th1-like', 'cells,', respectively])]). relacion([sujeto(['Our', data, thus, not, only]), verbo([provide]), complemento([new, evidence, for, another, type, of, 'CD4+', 'T', cell, 'plasticity,', but, also, have, a, potential, to, impact, the, development, of, a, new, direction, in, immunotherapy, of, allergic, diseases])]). relacion([sujeto(['To', identify, genes, and, pathways]), verbo([involved]), complemento([in, differentiation, of, 'Jurkat', 'T', cells, towards, 'Th1', and, 'Th2', subtypes, we, performed, comprehensive, transcriptome, analyses, of, 'Jurkat', 'T', cells, stimulated, with, various, stimuli, and, pathway, inhibitors])]). relacion([sujeto(['Calcium-dependent', activation, of, 'T', cells, using, 'CD3/CD28', and, 'PMA/CD3', stimulation]), verbo([induced]), complemento([a, 'Th1', expression, profile, reflected, by, increased, expression, of, 'T-bet,', 'RUNX3,', 'IL-2,', and, 'IFNγ,', whereas, 'calcium-independent', activation, via, 'PMA/CD28', induced, a, 'Th2', expression, profile, which, included, 'GATA3,', 'RXRA,', 'CCL1', and, 'Itk'])]). relacion([sujeto(['Knock', down, with, siRNA, and, gene, expression, profiling, in, the, presence, of, selective, kinase, inhibitors, showed, that, proximal, kinases, 'Lck', and, 'PKCθ', are, crucial, signaling, hubs, during, 'T', helper, cell, 'activation,']), verbo([revealed]), complemento([a, clear, role, for, 'Lck', in, 'Th1', development, and, for, 'PKCθ', in, both, 'Th1', and, 'Th2', development])]). relacion([sujeto(['Translation', towards, a, 'primary,', whole, blood, setting, and, purified, human, 'CD4+', 'T', cells, revealed, that, 'PMA/CD3', stimulation]), verbo([induced]), complemento([a, more, pronounced, 'Th1', 'specific,', 'Lck', and, 'PKCθ', dependent, 'IFNγ', 'production,', whereas, 'PMA/CD28', induced, 'Th2', specific, 'IL-5', and, 'IL-13', 'production,', independent, of, 'Lck', activation])]). relacion([sujeto(['PMA/CD3-mediated', skewing, towards, a, 'Th1', phenotype, was, also, reflected, in, mRNA, expression, of, the, master, transcription, factor, 'Tbet,', whereas, 'PMA/CD28-mediated', stimulation]), verbo([enhanced]), complemento(['GATA3', mRNA, expression, in, primary, human, 'CD4+', 'Tcells'])]). relacion([sujeto(['PMA/CD3', stimulation]), verbo([enhances]), complemento([a, 'Th1-like', response, in, an, 'Lck', and, 'PKCθ', dependent, 'fashion,', whereas, 'PMA/CD28', stimulation, results, in, a, 'Th2-like', phenotype, independent, of, the, proximal, 'TCR-tyrosine', kinase, 'Lck'])]). relacion([sujeto(['The', pathogenesis, of, 'DILI', usually]), verbo([involves]), complemento([the, participation, of, the, parent, drug, or, metabolites, that, either, affect, cellular, function, or, elicit, an, immune, response])]). relacion([sujeto(['However,', the, mechanisms]), verbo([leading]), complemento([to, 'DILI', are, unknown, in, most, cases])]). relacion([sujeto(['Methimazole', '(', 'MTZ)', is, used, as, an, antithyroid, drug, and, is, well, known, to]), verbo([have]), complemento([induced, liver, injuries, such, as, cholestatic, hepatitis, in, a, small, number, of, human, cases])]). relacion([sujeto(['Immune-mediated', reactions, were, also]), verbo([suggested]), complemento([to, play, a, role, in, 'MTZ-induced', acute, liver, 'injury,', but, the, mechanism, underlying, this, process, has, not, been, elucidated])]). relacion([sujeto(['The', hepatic, expression, of, mRNA, for, 'Th2', 'cell-related', 'factors,', such, as, 'GATA-binding', 'protein,', macrophage, inflammatory, 'protein-2', '(', 'MIP-2)', and, plasma, 'IL-4', 'levels,', as, well, as, plasma, 'AST', and, 'ALT', 'levels,', was, significantly]), verbo([increased]), complemento([in, mice, treated, with, 'MTZ'])]). relacion([sujeto(['These', changes, were, markedly]), verbo([enhanced]), complemento([by, 'pre-treatment', with, 'L-buthionine', sulfoximine, '(', 3, mmol, 'kg⁻¹,', i])]). relacion([sujeto([')']), verbo([suppressed]), complemento([the, hepatotoxic, effect, of, 'MTZ'])]). relacion([sujeto(['In', 'conclusion,', this]), verbo([report]), complemento([is, the, first, to, demonstrate, that, 'Th2', 'cytokine-mediated', immune, responses, are, involved, in, 'MTZ-induced', acute, liver, injury, in, mice])]). relacion([sujeto(['Haploinsufficiency', of, a, more, proximal, 'region,', located, on, 10, 'p13-10p14,', designated, as, 'DGCR2', is]), verbo([associated]), complemento([with, congenital, heart, defects, and, thymus, 'hypoplasia/aplasia', or, 'T', cell, defect])]). relacion([sujeto(['We', describe, a, patient, showing, facial, 'dysmorphisms,', delayed, psychomotor, development, and, bilateral, sensorineural, hearing]), verbo([loss]), complemento([and, carrying, a, 10, p14, 'deletion,', the, smallest, deletion, found, in, the, literature, so, far])]). relacion([sujeto(['On', the, basis, of, the, revision, of, the, other, cases]), verbo([reported]), complemento([in, the, literature, with, a, deletion, including, the, 10, p14, 'region,', we, suggest, that, 'GATA3', 'haploinsufficiency,', although, not, recorded, for, each, 'patient,', is, responsible, for, deafness])]). relacion([sujeto(['We', propose, that, the, auditory, periphery, '(', basilar, 'papilla,', organ, of, 'Corti)', evolved, by, transforming, a, newly, created, and, redundant, vestibular, '(', 'gravistatic)', endorgan, into, a, sensory, epithelium, that, could]), verbo([respond]), complemento([to, sound, instead, of, gravity])]). relacion([sujeto(['Evolution', of, mammalian, auditory, '(', spiral, 'ganglion)', neurons, coincides, with, 'GATA3', being, a, transcription, factor]), verbo([found]), complemento([selectively, in, the, auditory, afferents])]). relacion([sujeto(['For', the, auditory, information, to, be, 'processed,', the, 'CNS']), verbo([required]), complemento([a, dedicated, center, for, auditory, 'processing,', the, auditory, nuclei])]). relacion([sujeto(['It', is, not, known, whether, the, auditory, nucleus, is, ontogenetically, related, to, the, vestibular, or, electroreceptive, 'nuclei,', two, sensory, systems]), verbo([found]), complemento([in, aquatic, but, not, in, amniotic, 'vertebrates,', or, a, 'de-novo', formation, of, the, rhombic, lip, in, line, with, other, novel, hindbrain, structures, such, as, pontine, nuclei])]). relacion([sujeto(['Like', other, novel, hindbrain, 'structures,', the, auditory, nuclei]), verbo([express]), complemento([exclusively, the, bHLH, gene, 'Atoh1,', and, loss, of, 'Atoh1', results, in, loss, of, most, of, this, nucleus, in, mice])]). relacion([sujeto(['Only', after, the, basilar, 'papilla,', organ, of, 'Corti', evolved, could, efferent, neurons, begin, to]), verbo([modulate]), complemento([their, activity])]). relacion([sujeto(['The', most, simplistic, interpretation, of, available, data]), verbo([suggest]), complemento([that, the, 'ear,', sensory, 'neurons,', auditory, 'nucleus,', and, efferent, neurons, have, been, transformed, by, altering, the, developmental, genetic, modules, necessary, for, their, development, into, a, novel, direction, conducive, for, sound, 'extraction,', 'conduction,', and, processing])]). relacion([sujeto(['The', inducible, subunits, change, the, cleavage, specificities, of, the, 'proteasome,', but, it, is, unclear, whether, they]), verbo([have]), complemento([functions, in, addition, to, this])]). relacion([sujeto(['The', purpose, of, the, present, study, was, to, determine, the, role, of, the, proteasome, in, 'general,', as, well, as, 'LMP7', and, 'MECL1', 'specifically,', with, regard, to, cytokine, production, by]), verbo([activated]), complemento([primary, splenocytes])]). relacion([sujeto(['Isolated', splenocytes, from, 'wild-type', and, 'LMP7/MECL1-/-', mice, were, treated, with, lactacystin, and]), verbo([activated]), complemento([with, 'PMA', and, ionomycin, and, subsequently, cytokine, mRNA, levels, were, quantified])]). relacion([sujeto(['The', present, study, demonstrates, that, 'LMP7/MECL1']), verbo([regulates]), complemento([the, expression, of, 'IFNγ,', 'IL4,', 'IL10,', 'IL2Rβ,', 'GATA3,', and, 't-bet'])]). relacion([sujeto(['Collectively,', the, present, study, demonstrates, that, 'LMP7', and, 'MECL1']), verbo([regulate]), complemento([cytokine, 'expression,', suggesting, this, system, represents, a, novel, mechanism, for, the, regulation, of, cytokines, and, cytokine, signaling])]). relacion([sujeto(['The', aim, of, this, study, was, to, investigate, the, effects, of, transcription, factors, 'T-bet,', 'GATA-3', in, the, pathogenesis, of, 'Hench-Schonlein', purpura, '(', 'HSP)', in, 'children,', the, relationship, between, 'CD4(+)CD25(+)regulatory', 'T', 'cells,', transcription, factor, 'FoxP3', and, the, development, of, child, 'HSP,', and, the, molecular, mechanisms, of, 'Th1/Th2', imbalance, of, child, 'HSP', at, acute, 'phase,', so, as, to, may]), verbo([provide]), complemento([a, new, approach, and, strategy, for, the, treatment, of, 'HSP', at, the, molecular, levels])]). relacion([sujeto(['This', study]), verbo([provides]), complemento([experimental, evidence, for, illustrating, the, pathogenesis, of, 'HSP', from, the, molecular, mechanism, of, 'Treg', cells, and, its, 'regulation,', and, also, provides, a, new, thinking, and, new, strategies, for, the, treatment, of, 'HSP', at, molecular, levels])]). relacion([sujeto(['Invariant', 'NKT', '(', 'iNKT)', cells, are, a]), verbo([conserved]), complemento(['αβTCR(+)', 'T', cell, population, that, can, swiftly, produce, large, amounts, of, 'cytokines,', thereby, activating, other, 'leukocytes,', including, neutrophilic, granulocytes, '(', 'neutrophils)'])]). relacion([sujeto(['In', this, 'study,', we, investigated, the, reverse, 'relationship,', showing, that, high, neutrophil, concentrations]), verbo([suppress]), complemento([the, iNKT, cell, response, in, mice, and, humans])]). relacion([sujeto(['Peripheral', 'Vα14', iNKT, cells, from, spontaneously, neutrophilic, mice, produced, reduced, cytokines, in, response, to, the, model, iNKT, cell, 'Ag', 'α-galactosyl', ceramide, and]), verbo([expressed]), complemento([lower, amounts, of, the, 'T-box', transcription, factor, 21, and, 'GATA3', transcription, factor, than, did, 'wild-type', controls])]). relacion([sujeto(['Transcription', factor, expression, was, also]), verbo([decreased]), complemento([in, primary, iNKT, cells, from, the, 'neutrophil-rich', bone, marrow, compared, with, spleen, in, 'wild-type', mice])]). relacion([sujeto(['In', 'vitro,', the, function, of, both, mouse, and, human, iNKT, cells, was]), verbo([inhibited]), complemento([by, coincubation, with, neutrophils])]). relacion([sujeto(['This']), verbo([required]), complemento(['cell-cell', contact, with, live, neutrophils])]). relacion([sujeto(['Neutrophilic', inflammation, in, experimental, peritonitis, in, mice]), verbo([decreased]), complemento([iNKT, cell, 'T-box', transcription, factor, 21, and, 'GATA3', expression, and, 'α-galactosyl', 'ceramide-induced', cytokine, production, in, vivo])]). relacion([sujeto(['Similarly,', iNKT, cells, from, the, human, peritoneal, cavity]), verbo([expressed]), complemento([lower, transcription, factor, levels, during, neutrophilic, peritonitis])]). relacion([sujeto(['Our', data]), verbo([reveal]), complemento([a, novel, regulatory, axis, whereby, neutrophils, reduce, iNKT, cell, 'responses,', which, may, be, important, in, shaping, the, extent, of, inflammation])]). relacion([sujeto(['During', pregnancy, the, maternal, immune, system]), verbo([has]), complemento([to, coordinate, uterine, 'spiral-artery', 'remodelling,', trophoblast, 'invasion,', and, acceptance, of, the, 'semi-allogenic', fetus, simultaneously])]). relacion([sujeto(['As', dysregulation, of, the, immune, system, is]), verbo([associated]), complemento([with, adverse, pregnancy, 'outcomes,', we, analysed, 'first-trimester', deciduas, of, pregnancies, for, immune, parameters, in, later, complicated, pregnancies])]). relacion([sujeto(['Higher', 'IL6', and, macrophage, mRNA, 'expression,', and, lower, ratios, of, regulatory, macrophages, were]), verbo([found]), complemento([in, 'first-trimester', deciduas, of, pregnancies, later, complicated, with, 'pregnancy-induced', hypertension])]). relacion([sujeto(['Lower', 'Gata3', '(', 'Th2)', mRNA, expression, was]), verbo([found]), complemento([in, deciduas, of, pregnancies, with, later, foetal, growth, restriction])]). relacion([sujeto(['Our', results]), verbo([suggest]), complemento([that, adverse, pregnancy, outcomes, are, associated, with, immunological, disturbances, in, 'first-trimester', deciduas])]). relacion([sujeto(['The', allergic, rhinitis, rat, model, was]), verbo([induced]), complemento([with, ovalbumin])]). relacion([sujeto(['The', imbalance, of, transcription, factor, 'GATA-3', and, 'T-bet']), verbo([has]), complemento([a, close, correlation, with, the, eosinophil, 'count,', and, may, play, a, key, role, in, the, formation, of, allergic, rhinitis])]). relacion([sujeto(['The', scaffold, protein, 'CARMA1', is]), verbo([required]), complemento([for, the, 'TCR-induced', lymphocyte, activation])]). relacion([sujeto(['We']), verbo([have]), complemento([found, that, the, adoptive, transfer, of, bone, marrow, cells, expressing, constitutively, active, 'CARMA1', results, in, lung, 'inflammation,', 'eosinophilia,', and, elevated, levels, of, 'IL-4,', 'IL-5,', and, 'IL-10', in, recipient, mice])]). relacion([sujeto(['In', 'contrast,', 'CARMA1-deficient', 'T', cells, are, defective, in, 'TCR-induced', expression, of, 'Th2', 'cytokines,']), verbo([suggesting]), complemento([that, 'CARMA1', preferentially, directs, 'Th2', differentiation])]). relacion([sujeto(['CARMA1', deficiency, affects, 'JunB', stability, resulting, in, its]), verbo([enhanced]), complemento([ubiquitination, and, degradation])]). relacion([sujeto(['In', 'contrast,', 'TCR-dependent', induction, of, 'GATA3', is]), verbo([suppressed]), complemento([at, the, transcriptional, level])]). relacion([sujeto(['We', also]), verbo([found]), complemento([that, supplementation, with, 'IL-4', partially, restored, 'GATA3', expression, in, 'CARMA1-deficient', 'CD4(+)', splenocytes, and, subsequently, production, of, 'GATA3-dependent', cytokines, 'IL-5', and, 'IL-13'])]). relacion([sujeto(['Therefore,', our, work]), verbo([provides]), complemento([the, mechanism, by, which, 'CARMA1', regulates, 'Th2', cell, differentiation])]). relacion([sujeto(['In', 'asthma,', 'T', helper, 2, '(', 'T(H)2)-type', cytokines, such, as, interleukin, '(', 'IL)-4,', 'IL-5,', and, 'IL-13', are, produced, by]), verbo([activated]), complemento(['CD4(+)', 'T', cells])]). relacion([sujeto(['We', determined, whether, 'RG-II']), verbo([regulates]), complemento([the, 'T(H)1/T(H)2', immune, response, by, using, an, 'ovalbumin-induced', murine, model, of, asthma])]). relacion([sujeto(['RG-II', reduced, 'IL-4', production, but]), verbo([increased]), complemento(['interferon-', gamma, 'production,', and, inhibited, 'GATA-3', gene, expression])]). relacion([sujeto(['RG-II', also]), verbo([inhibited]), complemento([asthmatic, reactions, including, an, increase, in, the, number, of, eosinophils, in, bronchoalveolar, lavage, 'fluid,', an, increase, in, inflammatory, cell, infiltration, in, lung, 'tissues,', airway, luminal, 'narrowing,', and, airway, hyperresponsiveness])]). relacion([sujeto(['This', study]), verbo([provides]), complemento([evidence, that, 'RG-II', plays, a, critical, role, in, ameliorating, the, pathogenic, process, of, asthmatic, inflammation, in, mice])]). relacion([sujeto(['These', findings]), verbo([provide]), complemento([new, insights, into, the, immunotherapeutic, role, of, 'RG-II', in, terms, of, its, effects, in, a, murine, model, of, asthma])]). relacion([sujeto(['To', study, mRNA, expression, of, 'immune-related', genes, '(', 'Foxp3,', 'GATA3,', 'CTLA4', and, 'T-bet)', in, peripheral, blood, of, the, patients, with, allergic, dermatitis]), verbo([induced]), complemento([by, trichloroethylene, '(', 'TCE)'])]). relacion([sujeto(['The', peripheral, blood, samples, were, collected, from, 8, healthy, workers, '(', control, 'group)', and, 8, patients, with, allergic, dermatitis]), verbo([induced]), complemento([by, 'TCE', '(', case, 'group)'])]). relacion([sujeto(['The', mRNA, expression, levels, of, 'Foxp3,', 'GATA3', and, 'CTLA4', genes]), verbo([increased]), complemento([by, 115, '%', ',', 97, '%', and, 241, '%', in, case, 'group,', as, compared, with, control, group, '(', 'P', &, 'lt;', 0.01, ')'])]). relacion([sujeto(['The', mRNA, expression, level, of, 'T-bet', gene]), verbo([decreased]), complemento([by, 47, '%', in, case, 'group,', as, compared, with, control, group, '(', 'P', &, 'lt;', 0.01, ')'])]). relacion([sujeto(['The', mRNA, expression, levels, of, some, 'immune-related', genes, changed, in, patients, with, allergic, dermatitis]), verbo([induced]), complemento([by, 'TCE,', those, genes, may, play, an, important, role, in, 'TCE-induced', allergy])]). relacion([sujeto(['The', objective, of, the, present, study, was, to, evaluate, the, expression, of, 'T-box']), verbo([expressed]), complemento([in, 'T', cells, '(', 'T-bet)', and, 'GATA', binding, protein, 3, '(', 'GATA-3)', in, the, eutopic, endometrium, from, women, with, endometriosis])]). relacion([sujeto(['Eutopic', endometrial, tissues, from, patients, with, endometriosis]), verbo([expressed]), complemento([lower, levels, of, 'T-bet', mRNA, and, high, levels, of, 'GATA-3', 'mRNA,', leading, to, a, significant, lower, 'T-bet/GATA-3', mRNA, ratio, '(', 'P<0'])]). relacion([sujeto(['These', results]), verbo([suggested]), complemento([that, 'T-bet', and, 'GATA-3', may, act, as, cytokine, regulatory, 'genes,', and, the, 'Th2-specific', transcription, 'factor,', 'GATA-3,', probably, plays, an, essential, role, in, the, immune, response, and, the, development, of, endometriosis])]). relacion([sujeto(['Changes', in, the, 'Th1/Th2', immune, balance, may, play, a, role, in]), verbo([increasing]), complemento([the, incidence, of, 'radiation-induced', toxicity])]). relacion([sujeto(['The', 'T-bet-deficient', mice, showed, an]), verbo([increased]), complemento([fibrotic, response, to, 'radiation,', characterized, by, higher, 'TGF-β1,', col3a1, 'expression,', and, collagen, deposition, in, mucosa, compared, with, 'wild-type', mice])]). relacion([sujeto(['This', response, was]), verbo([associated]), complemento([with, drastically, lower, expression, of, 'IFN-γ,', the, hallmark, 'Th1', cytokine])]). relacion([sujeto(['Irradiation']), verbo([induces]), complemento(['Th2', 'polarization,', and, the, 'Th2', immune, response, may, play, a, role, in, potentiating, 'irradiation-induced', intestinal, collagen, deposition])]). relacion([sujeto(['CASPASE-1', expression, and, a, relative]), verbo([increase]), complemento([in, 'T(h)1', transcripts, in, 'AT', were, strongly, associated, with, insulin, resistance, and, impairments, in, glucose, homeostasis])]). relacion([sujeto(['Our', data]), verbo([suggest]), complemento([that, 'NLRP3', inflammasome, activation, and, a, 'T(h)1', shift, in, the, 'T', cell, population, in, 'AT', of, obese, subjects, is, related, to, insulin, resistance, and, impaired, glucose, 'metabolism,', which, may, be, explained, by, 'AT', inflammatory, processes])]). relacion([sujeto(['Although', the, diagnosis, of, prostatic, adenocarcinoma, is, straightforward, in, most, 'cases,', due, to, earlier, detection, of, the, disease, in, the, modern, 'era,', pathologists]), verbo([have]), complemento([become, increasingly, challenged, in, diagnosing, small, foci, of, cancer, when, only, a, few, atypical, glands, are, present, in, needle, biopsies])]). relacion([sujeto(['Immunohistochemistry']), verbo([has]), complemento([therefore, become, an, essential, tool, in, the, evaluation, of, such, foci, to, confirm, the, absence, of, basal, cells])]). relacion([sujeto(['Furthermore,', 'α-methylacyl-CoA', 'racemase,', a, marker]), verbo([found]), complemento([to, be, overexpressed, in, the, cytoplasm, of, prostatic, adenocarcinoma, 'glands,', is, also, commonly, used, in, routine, practice])]). relacion([sujeto(['The', expressions, of, tumor, necrosis, 'factor-α', '(', 'TNF-α),', 'interleukin-10', '(', 'IL-10),', 'T-box']), verbo([expressed]), complemento([in, 'T-cells', '(', 'T-bet),', and, 'GATA-binding', 'protein-3', '(', 'GATA-3)', were, detected, by, 'real-time', polymerase, chain, reaction, '(', 'RT-PCR)'])]). relacion([sujeto(['While', 'RT-PCR', showed, that, there, was, an]), verbo([increased]), complemento([level, of, 'TNF-α', mRNA, '(', 'P<0'])]). relacion([sujeto([1, ')', ',', an, elevated, ratio, of, 'T-bet/GATA-3,', and, a]), verbo([decreased]), complemento([level, of, 'IL-10', mRNA, in, 'PBMC', of, 'N', and, 'T', group, compared, to, 'B', group, '(', 'P', &, 'lt;0'])]). relacion([sujeto([1, ')', ;, and, after, treatment, with, 'Xiaoyin', 'Recipe,', 'IL-10', mRNA, level]), verbo([increased]), complemento(['(', 'P', &, 'lt;0'])]). relacion([sujeto([1, ')', ',', while, 'TNF-α', mRNA, level, and, 'T-bet/GATA-3', ratio]), verbo([decreased]), complemento([in, 'T', group, compared, to, 'N', group, '(', 'P', &, 'lt;0'])]). relacion([sujeto(['Xiaoyin', 'Recipe', for, psoriasis, could]), verbo([induce]), complemento([a, 'Th1/Th2', balance, drift, toward, 'Th2', in, 'PBMC', of, 'EAT', rats, and, thus, improve, the, conditions])]). relacion([sujeto(['We', herein]), verbo([report]), complemento([that, infection, with, 'Toxoplasma', 'gondii,', an, intracellular, 'protozoan,', is, capable, of, ameliorating, the, spontaneous, development, of, arthritis, in, 'IL-1Ra-deficient', mice])]). relacion([sujeto(['The', onset, of, arthritis, development, was, delayed, and, the, severity, score, of, arthritis, was, significantly]), verbo([suppressed]), complemento([in, 'T'])]). relacion([sujeto(['Expression', of, 'IL-12p40', mRNA, from, 'CD11c(+)', cells, of, mesenteric, lymph, nodes, '(', 'mLN)', and, spleen, markedly]), verbo([increased]), complemento([at, 1, week, after, peroral, infection])]). relacion([sujeto(['gondii-infected', mice]), verbo([expressed]), complemento([significantly, high, levels, of, 'T-bet', and, gamma, interferon, '(', 'IFN-γ)', mRNA, in, both, mLN, and, spleen])]). relacion([sujeto(['Levels', of, 'GATA-3/IL-4', mRNA, or, 'RORγt/IL-17', mRNA]), verbo([decreased]), complemento([in, the, infected, 'mice,', indicating, 'Th1', cell, polarization, and, the, reduction, of, 'Th2', and, 'Th17', cell, polarization])]). relacion([sujeto(['To', determine, the, effect, of, regulatory, 'T', cells, on, the, ratio, of, 'Th1/Th2', differentiation, in, peripheral, blood, mononuclear, cells, of, chronic, hepatitis, 'B', 'patients,', 'FoxP3,', the, essential, transcription, factor, for, 'Tcells', differentiation, and, 'function,', was, knocked, down, by, 'FoxP3', 'siRNA,', which, was, affirmed, by, 'real-time', polymerase, chain, reaction, for]), verbo([decreased]), complemento([expression, of, 'FoxP3'])]). relacion([sujeto(['Then,', at, different, time, 'points,', comparing, with, control, 'groups,', we, detected]), verbo([enhanced]), complemento([lymphocyte, proliferation, and, 'up-regulated', 'Th1-type', 'cytokines,', but, 'down-regulated', 'Th2-type', cytokines, by, 'ELISA'])]). relacion([sujeto(['Finally,', to, research, the]), verbo([involved]), complemento(['mechanisms,', an, increased, ratio, of, 'T-bet/GATA-3', mRNA, expression, was, found, by, 'real-time', polymerase, chain, reaction])]). relacion([sujeto(['Our', results]), verbo([suggest]), complemento([that, 'siRNA-mediated', knockdown, of, 'FoxP3', could, regulate, the, immune, balance, of, 'Th1/Th2', in, chronic, hepatitis, 'B', 'patients,', which, may, be, mediated, partly, by, regulating, transcription, factors, 'T-bet', and, 'GATA-3'])]). relacion([sujeto(['In', this, 'report,', we, demonstrate, that, estrogen]), verbo([activates]), complemento([expression, of, 'S6K1', via, estrogen, receptor, '(', 'ER)α', in, 'ER-positive', breast, cancer, cells])]). relacion([sujeto(['We', also, show, that, estrogen]), verbo([acts]), complemento([on, the, proximal, promoter, of, the, 'S6K1', gene, in, a, mechanism, involving, the, transcriptional, factor, 'GATA-3'])]). relacion([sujeto(['Finally,', we]), verbo([provide]), complemento([data, that, support, the, importance, of, estrogenic, regulation, of, 'S6K1', expression, in, breast, cancer, cell, proliferation])]). relacion([sujeto(['S6K1', directly]), verbo([phosphorylates]), complemento([and, regulates, 'ligand-independent', activity, of, 'ERα,', while, 'ERα', upregulates, 'S6K1', expression])]). relacion([sujeto(['Furthermore,', the, 'co-dependent', association, between, 'S6K1', and, 'ERα', may, be, exploited, in, the, development, of]), verbo([targeted]), complemento([breast, cancer, therapies])]). relacion([sujeto(['Antipsychotic', drugs, '(', 'APDs)', are, widely, used, to, alleviate, a, number, of, psychic, disorders, and, may]), verbo([have]), complemento([immunomodulatory, effects])]). relacion([sujeto(['Our', results, indicated, that, clozapine, can]), verbo([suppress]), complemento([the, stimulated, production, of, 'IFN-γ', by, 30.62, '%', ',', whereas, haloperidol, weakly, enhances, the, expression, of, 'IFN-γ'])]). relacion([sujeto(['Furthermore,', clozapine, and, risperidone]), verbo([inhibited]), complemento([the, 'T-bet', mRNA, and, protein, 'expression,', which, are, critical, to, 'Th1', differentiation])]). relacion([sujeto(['Also,', clozapine, can]), verbo([enhance]), complemento([the, expression, of, 'Signal', 'Transducer', and, 'Activator', of, 'Transcription', 6, and, 'GATA3,', which, are, critical, for, the, differentiation, of, 'Th2', cells])]). relacion([sujeto(['The', results]), verbo([suggested]), complemento([that, clozapine, and, haloperidol, may, induce, different, immunomodulatory, effects, on, the, immune, system])]). relacion([sujeto(['Although', it, is, well, documented, that, 'GATA-3', is]), verbo([expressed]), complemento([in, 'HSCs,', a, role, for, 'GATA-3', in, any, prethymic, progenitor, cell, has, not, been, established])]). relacion([sujeto(['Furthermore,', 'Gata3', mutant, hematopoietic, progenitor, cells, fail, to, be]), verbo([recruited]), complemento([into, an, increased, cycling, state, after, 5, -, 'fluorouracil-induced', myelosuppression])]). relacion([sujeto(['Therefore,', 'GATA-3', is]), verbo([required]), complemento([for, the, maintenance, of, a, normal, number, of, 'LT-HSCs', and, for, their, entry, into, the, cell, cycle])]). relacion([sujeto(['The', pathogenesis, of, focal, segmental, glomerulosclerosis, '(', 'FSGS)', appears, to, be]), verbo([associated]), complemento([with, 'type-2', cytokines, and, podocyte, dysfunction])]). relacion([sujeto(['Adriamycin', injection, resulted, in, albuminuria, and]), verbo([increased]), complemento([serum, creatinine, in, association, with, loss, of, glomerular, podocin, and, podoplanin, 'expression,', which, is, consistent, with, podocyte, dysfunction])]). relacion([sujeto(['In', association, with, the, expression, of, fibrogenic, 'transcripts,', we, observed, 'peri-glomerular', expression, of, 'α-smooth', muscle, actin, '(', 'α-SMA),', indicating, 'epithelial-to-mesenchymal', 'transition,', and]), verbo([increased]), complemento([expression, of, proliferating, cell, nuclear, antigen, '(', 'PCNA)', in, tubular, 'cells,', suggesting, intense, proliferative, activity])]). relacion([sujeto(['Previous', immunization, with, 'PS']), verbo([inhibited]), complemento([albuminuria, and, serum, creatinine, in, association, with, the, preservation, of, podocyte, proteins, and, inhibition, of, fibrogenic, transcripts, and, the, expression, of, 'α-SMA', and, 'PCNA', proteins])]). relacion([sujeto(['Tissue', analysis, also, revealed, that, 'PS', treatment]), verbo([induced]), complemento([expression, of, mRNA, for, 'GD3', 'synthase,', which, is, a, glycosiltransferase, related, to, the, synthesis, of, 'GD3,', a, ganglioside, associated, with, podocyte, physiology])]). relacion([sujeto(['In', 'addition,', 'PS', treatment]), verbo([inhibited]), complemento([the, influx, of, inflammatory, 'CD8(pos)', and, 'CD11b(pos)', cells, to, kidney, tissue])]). relacion([sujeto([acnes, can]), verbo([inhibit]), complemento(['FSGS', 'pathogenesis,', suggesting, that, immunomodulation, can, represent, an, alternative, approach, for, disease, management])]). relacion([sujeto(['NF', erythroid, 2, -, related, factor, 2, '(', 'Nrf2)', is, a, transcription, factor, that]), verbo([mediates]), complemento([the, upregulation, of, a, battery, of, cytoprotective, genes, in, response, to, cell, stress])]). relacion([sujeto(['Recent', studies, showed, that, 'Nrf2', also]), verbo([modulates]), complemento([immune, responses, and, exhibits, 'anti-inflammatory', activity])]). relacion([sujeto(['In', this, 'article,', we, demonstrate, that, a, common, food, 'preservative,', 'tert-butylhydroquinone,', can]), verbo([activate]), complemento(['Nrf2', in, 'T', 'cells,', as, evidenced, by, 'Nrf2', binding, to, the, antioxidant, response, element, and, the, subsequent, upregulation, of, 'Nrf2', target, genes])]). relacion([sujeto(['The', activation, of, 'Nrf2']), verbo([suppresses]), complemento(['IFN-γ', 'production,', while, inducing, the, production, of, the, 'Th2', cytokines, 'IL-4,', 'IL-5,', and, 'IL-13'])]). relacion([sujeto(['Nrf2', activation, also]), verbo([suppresses]), complemento(['T-bet', 'DNA', binding, and, promotes, 'GATA-binding', protein, 3, 'DNA', binding])]). relacion([sujeto(['Collectively,', the, present, studies]), verbo([suggested]), complemento([that, 'Nrf2', activation, skews, 'CD4(+)', 'T', cells, toward, 'Th2', differentiation, 'and,', 'thus,', represents, a, novel, regulatory, mechanism, in, 'CD4(+)', 'T', cells])]). relacion([sujeto(['Further', studies, are, needed, to, determine, whether, the, commercial, use, of, 'Nrf2', activators, as, food, preservatives]), verbo([promotes]), complemento([food, allergies, in, humans])]). relacion([sujeto(['ETP', 'ALL', was, characterized, by]), verbo([activating]), complemento([mutations, in, genes, regulating, cytokine, receptor, and, 'RAS', signalling, '(', 67, '%', of, 'cases;', 'NRAS,', 'KRAS,', 'FLT3,', 'IL7R,', 'JAK3,', 'JAK1,', 'SH2B3', and, 'BRAF),', inactivating, lesions, disrupting, haematopoietic, development, '(', 58, '%', ;, 'GATA3,', 'ETV6,', 'RUNX1,', 'IKZF1', and, 'EP300)', and, 'histone-modifying', genes, '(', 48, '%', ;, 'EZH2,', 'EED,', 'SUZ12,', 'SETD2', and, 'EP300)'])]). relacion([sujeto(['We', also, identified, new]), verbo([targets]), complemento([of, recurrent, mutation, including, 'DNM2,', 'ECT2L', and, 'RELN'])]). relacion([sujeto(['These', findings]), verbo([suggest]), complemento([that, addition, of, 'myeloid-directed', therapies, might, improve, the, poor, outcome, of, 'ETP', 'ALL'])]). relacion([sujeto(['This']), verbo([suggests]), complemento([that, 'co-ordinate', expression, of, 'T(H)2', 'cytokines,', under, the, control, of, 'GATA3', and, 'NFAT1', is, due, to, the, formation, of, a, chromatin, hub, by, 'DNA', looping])]). relacion([sujeto(['Pirfenidone', therapy]), verbo([induced]), complemento(['down-regulation', of, 'Th2', transcripts, and, proteins, '(', 'GATA3', and, 'IL-4),', without, affecting, significantly, 'Th1', genes, expression, '(', 'T-bet', and, 'IFN-γ)'])]). relacion([sujeto(['We']), verbo([found]), complemento([that, the, activated, form, of, p38, 'MAPK', '(', identified, by, 'Western', 'blot)', was, reduced, by, pirfenidone, 'treatment,', which, is, consistent, with, the, 'anti-Th2', activity, observed])]). relacion([sujeto(['Pirfenidone', reduced, 'GATA3']), verbo([nuclear]), complemento([localization, without, modifying, its, 'DNA', binding, activity, '(', evaluated, by, electrophoretic, mobility, shift, 'assay)'])]). relacion([sujeto(['The', mechanism]), verbo([involves]), complemento([p38, inhibition, and, regulation, of, 'GATA3', expression, and, translocation])]). relacion([sujeto(['The', complimentary, 'experiment,', 'CNC', inactivation, of, 'Bmp2,', 'Bmp4', and, 'Bmp7,', resulted, in, complete, or, partial]), verbo([loss]), complemento([of, multiple, 'CNC-derived', skeletal, 'elements,', revealing, a, crucial, requirement, for, 'Bmp', signaling, in, membranous, bone, and, cartilage, development])]). relacion([sujeto(['Importantly,', the, 'BIG', signature, was, reduced, in, 'Bmp', 'loss-of-function', 'mutants,', indicating, 'Bmp-regulated']), verbo([target]), complemento([genes, are, modulated, by, 'Bmp', dose])]). relacion([sujeto(['Chromatin', immunoprecipitation, '(', 'ChIP)', revealed, a, subset, of, the, 'BIG', 'signature,', including, 'Satb2,', 'Smad6,', 'Hand1,', 'Gadd45γ', and, 'Gata3,', that, was]), verbo([bound]), complemento([by, 'Smad1/5', in, the, developing, 'mandible,', revealing, direct, 'Smad-mediated', regulation])]). relacion([sujeto(['These', data, support, the, hypothesis, that, 'Bmp', signaling]), verbo([regulates]), complemento([craniofacial, skeletal, development, by, balancing, 'self-renewal', and, differentiation, pathways, in, 'CNC', progenitors])]). relacion([sujeto(['The']), verbo([nuclear]), complemento([expression, of, 'FOXO1', was, observed, in, most, of, the, normal, breast, tissues, and, 51.3, '%', of, the, malignant, breast, tissues])]). relacion([sujeto(['GATA3', and, 'Annexin-1', were]), verbo([expressed]), complemento([at, 73, '%', and, 24.6, '%', respectively, in, breast, cancer, tissues])]). relacion([sujeto(['Both', 'FOXO1', and, 'Annexin-1', expression, were, also, inversely]), verbo([associated]), complemento([with, 'HER2-overexpressing', tumors])]). relacion([sujeto(['FOXO1', expression, was, significantly]), verbo([associated]), complemento([with, both, 'GATA3', and, 'Annexin-1', expression])]). relacion([sujeto(['FOXO1', expression, in, breast, cancer, is]), verbo([regulated]), complemento([by, the, 'PI3K/Akt', pathway])]). relacion([sujeto(['The', expression, of, 'FOXO1', is, also]), verbo([associated]), complemento([with, 'GATA3', 'and/or', 'Annexin-1'])]). relacion([sujeto(['Restoring', or]), verbo([targeting]), complemento(['FOXO1', to, the, cell, nucleus, in, breast, cancer, tissues, may, improve, response, to, therapy, and, disease, outcome])]). relacion([sujeto(['These', candidate, causal, 'SNPs', and, pathways]), verbo([provided]), complemento([ten, hypothetical, biological, mechanisms])]). relacion([sujeto(['The', most, strongly]), verbo([associated]), complemento([pathway, concerned, 'HLA'])]). relacion([sujeto(['When', 'HLA', loci, were, 'excluded,', 'ICSNPathway', analysis]), verbo([provided]), complemento([one, hypothetical, biological, mechanism])]). relacion([sujeto(['To', identify, the, cells]), verbo([expressing]), complemento([the, 'FOXP3', 'protein,', double, immunostaining, was, performed, by, using, 'anti-FOXP3', antibody, and, 'anti-CD3', antibody])]). relacion([sujeto(['A', positive, correlation, with, 'GATA3+CD3+/T-bet+CD3+', ratio, and, 'FOXP3+CD3+/CD3+', ratio]), verbo([suggests]), complemento([the, role, of, local, regulatory, 'T', cells, as, a, minimal, control, of, the, chronic, allergen, exposure, in, nasal, mucosa])]). relacion([sujeto(['This', study, was, conducted, to, investigate, the, effect, of, morphine, on, 'CD4-positive', 'T', cells, differentiation, and, the, transcriptional, factors]), verbo([induced]), complemento([by, phorbol, myristate, acetate, '(', 'PMA)', and, ionomycin])]). relacion([sujeto(['Th1', and, 'Th2', 'cells,', levels, of, 'INF-γ,', 'IL-2,', 'IL-4', and, the, activities, of, 'T-bet', and, 'GATA3', were, significantly]), verbo([increased]), complemento([after, incubation, with, 'PMA', and, ionomycin])]). relacion([sujeto(['However,', the, number, of, 'Th1', 'cells,', 'Th1/', 'Th2,', the, levels, of, 'INF-γ', and, 'INF-γ/IL-4,', and, the, activities, and, protein, levels, of, 'T-bet', and, 'GATA3', were]), verbo([decreased]), complemento([after, incubation, with, 'PMA', and, ionomycin, in, the, presence, of, morphine])]). relacion([sujeto(['Morphine']), verbo([has]), complemento([a, negative, effect, on, 'Th', cell, balance, induced, by, 'PMA', and, 'ionomycin,', the, mechanism, is, related, to, 'T-bet', and, 'GATA3'])]). relacion([sujeto([5, ')', exposure, resulted, in]), verbo([increased]), complemento(['CXCR3-expressing', 'CD4(+)', and, 'CD8(+)', 'T', cells, in, the, 'lungs,', 'spleen,', and, blood, with, elevation, in, 'CD11c(+)', macrophages, in, the, lung, and, oxidized, derivatives, of, 1, -, 'palmitoyl-2-arachidonyl-sn-glycero-3-phosphorylcholine', in, 'wild-type', mice])]). relacion([sujeto(['CXCR3', deficiency]), verbo([decreased]), complemento(['T', cells, in, the, lung])]). relacion([sujeto(['GFP(+)', regulatory, 'T', cells]), verbo([increased]), complemento([with, 'PM(2'])]). relacion([sujeto([5, ')', -, treated, macrophages, demonstrated]), verbo([enhanced]), complemento(['T', cell, proliferation])]). relacion([sujeto([5, ')', potentiates, a, proinflammatory, 'Th1', response]), verbo([involving]), complemento([increased, homing, of, 'CXCR3(+)', 'T', effector, cells, to, the, lung, and, modulation, of, systemic, 'T', cell, populations])]). relacion([sujeto(['Moreover,', fine, particles]), verbo([induced]), complemento([significant, increase, of, 'IL-4', and, 'IL-13', and, decrease, of, 'IFN-γ', in, myocardium, of, rats])]). relacion([sujeto(['The', variations, of, these, cytokines, demonstrated, the, imbalance, of, 'Th1', and, 'Th2', cytokines, existed, in, cardiac, injuries]), verbo([induced]), complemento([by, fine, particle])]). relacion([sujeto(['The', imbalance, of, 'Th1/Th2', cytokines, might, be, one, of, the, mechanisms, of, immunotoxicity, of, cardiovascular, system]), verbo([induced]), complemento([by, ambient, fine, particles])]). relacion([sujeto(['Insufficient', 'Treg', and, 'Th1', cells, may, be]), verbo([associated]), complemento([with, the, allergic, inflammation, that, may, be, attributed, to, the, 'Th2', immune, response, in, patients, suffering, from, 'AR', who, are, sensitive, to, olive, pollen])]). relacion([sujeto(['We', hypothesize, that, in, clinically, quiescent, 'SLE', 'patients,', the, mRNA, level, of]), verbo([target]), complemento([genes, in, the, urinary, sediment, is, an, early, indicator, of, disease, flare])]). relacion([sujeto(['The', mRNA, level, of, eight, 'pre-defined']), verbo([target]), complemento([genes, in, their, urinary, sediment, before, disease, flare, was, compared, to, 19, matched, controls, with, no, disease, flare, during, the, same, period])]). relacion([sujeto(['Before', disease, 'flare,', there, was, a, significant]), verbo([increase]), complemento([in, the, mRNA, level, of, monocyte, chemotactic, protein, '(', 'MCP)-1', and, forkhead, box, 'P3', '(', 'FOXP3),', and, decrease, in, interleukin, '(', 'IL)-17', and, 'GATA-3,', in, the, urinary, sediment])]). relacion([sujeto(['The', mRNA, level, of, 'FOXP3', in, urinary, sediment]), verbo([increases]), complemento([8, weeks, prior, to, a, 'flare,', which, precedes, the, corresponding, change, in, serum, complement, and, 'anti-DNA', antibody, 'titer,', while, that, of, 'MCP-1,', 'IL-17,', and, 'GATA3', began, to, change, 4, weeks, prior, to, a, flare])]). relacion([sujeto(['Monitoring', of, 'MCP-1,', 'IL-17,', 'GATA-3', and, 'FOXP3', mRNA, level, in, urinary, sediment, may]), verbo([provide]), complemento([an, early, clue, for, detecting, disease, flare, in, 'SLE', patients])]). relacion([sujeto(['We', show, that, the, 'BRCA1-GATA3', interaction, is, important, for, the, repression, of, genes]), verbo([associated]), complemento([with, 'triple-negative', and, 'basal-like', breast, cancer, '(', 'BLBCs)', including, 'FOXC1,', and, that, 'GATA3', interacts, with, a, 'C-terminal', region, of, 'BRCA1'])]). relacion([sujeto(['We', demonstrate, that, 'FOXC1', is, an, essential, survival, factor]), verbo([maintaining]), complemento([the, proliferation, of, 'BLBCs', cell, lines])]). relacion([sujeto(['We', show, that, 'BRCA1', and, 'GATA3']), verbo([interact]), complemento([on, the, 'FOXC1', promoter, and, that, 'BRCA1', requires, 'GATA3', for, recruitment, to, this, region])]). relacion([sujeto(['This', interaction]), verbo([requires]), complemento([fully, functional, 'BRCA1', as, a, mutant, 'BRCA1', protein, is, unable, to, localize, to, the, 'FOXC1', promoter, or, repress, 'FOXC1', expression])]). relacion([sujeto(['We', demonstrate, that, this, 'BRCA1-GATA3', repression, complex, is, not, a, 'FOXC1-specific', phenomenon, as, a, number, of, other, genes]), verbo([associated]), complemento([with, 'BLBCs', such, as, 'FOXC2,', 'CXCL1', and, 'p-cadherin', were, also, repressed, in, a, similar, manner])]). relacion([sujeto(['Finally,', we, demonstrate, the, importance, of, our, findings, by, showing, that]), verbo([loss]), complemento([of, 'GATA3', expression, or, aberrant, 'FOXC1', expression, contributes, to, the, drug, resistance, and, 'epithelial-to-mesenchymal', 'transition-like', phenotypes, associated, with, aggressive, 'BLBCs'])]). relacion([sujeto(['All', four, subpopulations, produced, 'interleukin-4', '(', 'IL-4)', and, 'IL-13,', whereas, only, the, 'CD62L(lo)CXCR3(lo)', population, produced, 'IL-5', accompanied, by]), verbo([increased]), complemento(['H3-K4', methylation, at, the, 'Il5', gene, locus])]). relacion([sujeto(['The', transcription, factor, 'Eomesodermin', '(', encoded, by, 'Eomes)', was, highly]), verbo([expressed]), complemento([in, memory, 'Th2', 'cells,', whereas, its, expression, was, selectively, downregulated, in, the, 'IL-5-producing', cells])]). relacion([sujeto(['Il5', expression, was]), verbo([enhanced]), complemento([in, 'Eomes-deficient', 'cells,', and, 'Eomesodermin', was, shown, to, interact, with, the, transcription, factor, 'GATA3,', preventing, 'GATA3', binding, to, the, 'Il5', promoter])]). relacion([sujeto(['Memory', 'Th2', 'cell-dependent', airway, inflammation, was, attenuated, in, the, absence, of, the, 'CD62L(lo)CXCR3(lo)', population, but, was]), verbo([enhanced]), complemento([by, 'Eomes-deficient', memory, 'Th2', cells])]). relacion([sujeto(['Thus,', 'IL-5', production, in, memory, 'Th2', cells, is]), verbo([regulated]), complemento([by, 'Eomesodermin', via, the, inhibition, of, 'GATA3', activity])]). relacion([sujeto(['Contact', hypersensitivity, '(', 'CHS)', is, thought, to, be]), verbo([associated]), complemento([mainly, with, the, activation, of, 'T', helper, '(', 'Th)', type, 1, cells])]). relacion([sujeto(['However,', evidence, also]), verbo([suggests]), complemento([that, 'Th', type, 2, cells, '(', 'Th2)', and, cytokines, play, roles, in, the, development, of, 'CHS', in, humans])]). relacion([sujeto(['The', expression, of, both, 'IL-5', and, 'IL-13', in, 'TNCB', 'sensitized/challenged', skin, tissues, and, the, 'IgE', response, after, challenge, were, obviously]), verbo([increased]), complemento([in, the, 'GATA-3', 'Tg', 'mice,', whereas, the, expression, of, 'IFN-γ', was, identical, in, the, challenged, skin, tissues, of, 'GATA-3-Tg', and, 'WT', mice])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, 'GATA-3-induced', 'Th2-dominant', responses, play, a, critical, role, in, the, pathogenesis, of, allergic, types, of, 'dermatitis,', such, as, atopic, 'dermatitis,', and, may, lead, to, useful, new, drug, development, in, the, future])]). relacion([sujeto(['Autonomic', neuron, development, is, controlled, by, a, network, of, transcription, 'factors,', which, is]), verbo([induced]), complemento([by, bone, morphogenetic, protein, signalling, in, neural, crest, progenitor, cells])]). relacion([sujeto(['Recent', findings, demonstrate, that, the, transcription, factors]), verbo([acting]), complemento([in, the, initial, specification, and, differentiation, of, sympathetic, neurons, are, also, important, for, the, proliferation, of, progenitors, and, immature, neurons, during, neurogenesis])]). relacion([sujeto(['Taken', 'together,', transcription, factors, previously, shown, to]), verbo([act]), complemento([in, initial, neuron, specification, and, differentiation, display, a, much, broader, spectrum, of, 'functions,', including, control, of, neurogenesis, and, the, maintenance, of, subtype, characteristics, and, survival, of, mature, neurons])]). relacion([sujeto(['The', transcription, factor, 'GATA1', is, known, to, play, an, essential, role, in, 'hematopoiesis,', but, its, other, roles]), verbo([have]), complemento([not, been, well, characterized])]). relacion([sujeto(['GATA1', mRNA, was]), verbo([found]), complemento([in, ovine, conceptuses, and, endometrial, epithelial, regions, of, 'Day', 15, '(', 'Day', 0, =, day, of, 'estrus)', cyclic, and, 'Days', 15, ',', 17, ',', and, 21, pregnant, ovine, uteri])]). relacion([sujeto(['GATA1', mRNA, was, strongly]), verbo([expressed]), complemento([in, conceptuses, on, 'Day', 21, ',', when, trophoblast, attachment, to, the, maternal, endometrium, progressed])]). relacion([sujeto(['To', localize, 'GATA1', 'mRNA,', ovine, conceptuses, and, pregnant, uteri, were, subjected, to, in, situ, hybridization, on, 'Days', 15, ',', 17, ',', and, 21, ',', confirming, that, 'GATA1', mRNA, was]), verbo([expressed]), complemento([in, trophoblasts, and, uterine, endometrial, epithelial, cells, in, these, gestation, days])]). relacion([sujeto(['These', observations, indicate, that, 'GATA1', exists, in, the, ovine, conceptus, and, uterus, during, the, 'peri-attachment', 'period,', and]), verbo([suggest]), complemento([that, 'GATA1', is, integral, to, conceptus, and, endometrial, development, through, the, regulation, of, 'GATA2', and, possibly, other, developmentally, important, genes])]). relacion([sujeto(['We']), verbo([have]), complemento([previously, shown, that, 'Hedgehog', '(', 'Hh)', signalling, in, the, thymus, decreases, the, 'CD4:CD8', 'single-positive', '(', 'SP)', thymocyte, ratio])]). relacion([sujeto(['Here,', we, present, data, indicating, that, 'double-positive', '(', 'DP)', thymocytes, are, 'Hh-responsive', and, that, 'thymocyte-intrinsic', 'Hh', signalling, plays, a, role, in]), verbo([modulating]), complemento([the, production, of, 'CD4(+)', '(', 'SP4),', 'CD8(+)', '(', 'SP8)', and, unconventional, 'T-cell', subsets])]). relacion([sujeto(['Additionally,', stimulation, or, withdrawal, of, 'Hh', signals, in, the, 'WT', foetal, thymus, impaired, or]), verbo([enhanced]), complemento([upregulation, of, the, 'CD4', 'lineage-specific', transcription, factor, 'Gata3', respectively])]). relacion([sujeto(['These', data, together]), verbo([suggest]), complemento([that, 'Hh', signalling, may, play, a, role, in, influencing, the, later, stages, of, thymocyte, development])]). relacion([sujeto(['The', development, of, the, inner, ear, sensory, epithelia]), verbo([involves]), complemento([a, complex, network, of, transcription, factors, and, signaling, pathways, and, the, whole, process, is, not, yet, entirely, understood])]). relacion([sujeto(['GATA3', is, a, 'DNA-binding', factor, that, is, necessary, for, otic, morphogenesis, and, without, 'GATA3', variable, defects]), verbo([have]), complemento([been, observed, already, at, early, stages, in, mouse, embryos])]). relacion([sujeto(['However,', due, to, the, early, lethality, of, 'Gata3-deficient', 'embryos,', the, later, morphogenesis, and, sensory, development]), verbo([have]), complemento([remained, unclear])]). relacion([sujeto(['To']), verbo([gain]), complemento([information, of, these, later, processes, we, produced, 'drug-rescued', 'Gata3-/-', embryos, that, survived, up, to, late, gestation])]). relacion([sujeto(['In', the, more, severely, affected, 'ears,', the, development, of, the, separate, endolymphatic, domain]), verbo([arrested]), complemento([completely, whereas, the, remaining, vesicle, formed, an, empty, cavity, with, variable, 'forms,', but, without, any, distinguishable, otic, compartments, or, morphologically, distinct, sensory, organs])]). relacion([sujeto(['Our', results]), verbo([suggest]), complemento([that, 'GATA3', is, critical, for, normal, vestibular, and, cochlear, morphogenesis, and, that, it, is, especially, important, for, cochlear, sensory, differentiation])]). relacion([sujeto(['Pro-inflammatory', 'T', cells]), verbo([mediate]), complemento([autoimmune, demyelination, in, multiple, sclerosis])]). relacion([sujeto(['miR-128', and, 'miR-27b', were]), verbo([increased]), complemento([in, naïve, and, 'miR-340', in, memory, 'CD4(+)', 'T', cells, from, patients, with, multiple, 'sclerosis,', inhibiting, 'Th2', cell, development, and, favouring, 'pro-inflammatory', 'Th1', responses])]). relacion([sujeto(['These', effects, were]), verbo([mediated]), complemento([by, direct, suppression, of, 'B', lymphoma, 'Mo-MLV', insertion, region, 1, homolog, '(', 'BMI1)', and, 'interleukin-4', '(', 'IL4)', 'expression,', resulting, in, decreased, 'GATA3', 'levels,', and, a, 'Th2', to, 'Th1', cytokine, shift])]). relacion([sujeto(['Gain-of-function', experiments, with, these, 'micro-RNAs']), verbo([enhanced]), complemento([the, encephalitogenic, potential, of, 'myelin-specific', 'T', cells, in, experimental, autoimmune, encephalomyelitis])]). relacion([sujeto(['In', 'addition,', treatment, of, multiple, sclerosis, patient, 'T', cells, with, oligonucleotide, 'micro-RNA', inhibitors]), verbo([led]), complemento([to, the, restoration, of, 'Th2', responses])]). relacion([sujeto(['These', data, illustrate, the, biological, significance, and, therapeutic, potential, of, these, 'micro-RNAs', in]), verbo([regulating]), complemento(['T-cell', phenotypes, in, multiple, sclerosis])]). relacion([sujeto(['However,', some, aspects, of, fetal, 'TEC', differentiation, occur, in, 'Foxn1', 'mutants,']), verbo([suggesting]), complemento([the, existence, of, additional, transcriptional, regulators, of, 'TEC', differentiation])]). relacion([sujeto(['The', goal, of, this, study, was, to, identify, some, of, the, additional, candidate, transcription, factors, that, may, be]), verbo([involved]), complemento([in, the, specification, 'and/or', differentiation, of, 'TECs', during, fetal, development])]). relacion([sujeto(['We']), verbo([found]), complemento([that, 'Foxg1', and, 'Isl1', are, specifically, expressed, in, differentiating, 'TECs', during, fetal, and, postnatal, stages, of, thymus, development])]). relacion([sujeto(['In', 'addition,', we]), verbo([found]), complemento([differential, expression, of, 'Islet1', and, 'Foxn1', within, the, fetal, and, postnatal, 'TEC', population])]). relacion([sujeto(['Our', studies]), verbo([have]), complemento([identified, two, developmental, transcription, factors, that, are, excellent, candidate, regulators, of, thymic, epithelial, cell, specification, and, differentiation, during, fetal, development])]). relacion([sujeto(['Our', results]), verbo([suggest]), complemento([that, 'Foxg1', and, 'Isl1', may, play, a, role, in, the, regulation, of, 'TEC', differentiation, during, fetal, and, postnatal, stages])]). relacion([sujeto(['Our', results, also, demonstrate, heterogeneity, of, 'TECs', marked, by, the, differential, expression, of, transcription, 'factors,', potentially]), verbo([providing]), complemento([new, insights, into, the, regulation, of, 'TEC', differentiation])]). relacion([sujeto(['The', molecular, signaling, pathways, that, are]), verbo([involved]), complemento([in, determining, the, differentiation, of, the, pharyngeal, pouch, endoderm, into, parathyroid, cells, are, being, elucidated, by, studies, of, patients, with, hypoparathyroidism, and, appropriate, mouse, models])]). relacion([sujeto(['These', studies]), verbo([have]), complemento([revealed, important, roles, for, a, number, of, transcription, 'factors,', which, include, 'Tbx1,', 'Gata3,', 'Gcm2,', 'Sox3,', 'Aire1', and, members, of, the, homeobox, '(', 'Hox)', and, paired, box, '(', 'Pax)', families])]). relacion([sujeto(['At', 10, -, hour, after, the, first, 'challenge,', relative, quantitation, of, expression, of, 'T-bet', in, experimental, group, was]), verbo([increased]), complemento([markedly, and, there, was, significant, difference, compared, with, contol, group, '(', 't=4'])]). relacion([sujeto(['The', amount, of, expression, of, 'T-bet', at, 10, -, hour, after, first, challenge, was]), verbo([increased]), complemento([significantly, compared, with, it, at, the, end, of, sensitization, '(', 't=', 5.27, ',', 'P<0'])]). relacion([sujeto(['while,', the, expression, of, 'GATA-3', at, 10, -, hour, after, final, challenge, was, markedly]), verbo([increased]), complemento([compared, with, it, at, the, end, of, sensitization, '(', 't=', 3.51, ',', 'P<0'])]). relacion([sujeto(['It', is, thought, that, the, development, of, allergic, rhinitis, is, a, successive, and, sequencing, kinetic, 'course,', and, imbalance, of, expression, of, 'GATA-3', and, 'T-bet', may, be, genetic, base, on, allergic, 'rhinitis,', both, 'GATA-3', and, 'T-bet', were]), verbo([involved]), complemento([in, allergic, rhinitis, only, in, different, phase, of, development, of, allergic, rhinitis])]). relacion([sujeto(['Glial', cells, missing, 'B', '(', 'GCMB)', is, a, transcription, factor, that, is]), verbo([expressed]), complemento([in, the, parathyroid, hormone, '(', 'PTH)-secreting', cells, of, the, parathyroid, glands])]). relacion([sujeto(['Several', mutations, in, 'GCMB']), verbo([have]), complemento([been, reported, to, cause, hypoparathyroidism, '(', 'HP)'])]). relacion([sujeto(['The', identified, 'GCMB', mutant, was, characterized, by, functional, studies, including]), verbo([nuclear]), complemento(['localization,', electrophoretic, mobility, shift, assays, '(', 'EMSA)', and, luciferase, reporter, 'assays,', and, homology, modelling, was, performed, to, generate, a, 'three-dimensional', structural, model, for, the, 'DNA-binding', domain, of, 'GCMB', to, predict, the, structural, consequences, of, the, identified, mutation])]). relacion([sujeto(['The', 'C106R', mutant, of, 'GCMB', failed, to]), verbo([interact]), complemento([with, the, 'DNA', consensus, recognition, 'motif,', as, determined, by, 'EMSA'])]). relacion([sujeto(['Consistent', with, the, 'EMSA', 'findings,', homology, modelling, analysis]), verbo([suggested]), complemento([that, replacement, of, cysteine, 106, with, arginine, would, interfere, with, 'DNA', binding])]). relacion([sujeto(['We']), verbo([have]), complemento([identified, a, novel, 'GCMB', mutation, that, may, explain, 'AD-HP', in, our, family])]). relacion([sujeto(['However,', the, exact, mechanism, by, which, this, heterozygous, mutation]), verbo([leads]), complemento([to, the, disease, in, the, described, family, remains, to, be, elucidated])]). relacion([sujeto(['Many', transformed, lymphoma, cells, show, 'immune-phenotypes', resembling, the, corresponding, normal, 'lymphocytes;', 'thus,', they]), verbo([provide]), complemento([a, guide, for, proper, diagnosis, and, present, promising, routes, to, improve, their, pathophysiologic, understanding, and, to, identify, novel, therapeutic, targets])]). relacion([sujeto(['Here,', we]), verbo([report]), complemento([that, 'microRNA-135b', '(', 'miR-135b)', mediates, 'nucleophosmin-anaplastic', lymphoma, kinase, '(', 'NPM-ALK)-driven', oncogenicity, and, empowers, 'IL-17-producing', immunophenotype, in, anaplastic, large, cell, lymphoma, '(', 'ALCL)'])]). relacion([sujeto(['NPM-ALK', oncogene, strongly]), verbo([promoted]), complemento([the, expression, of, 'miR-135b', and, its, host, gene, 'LEMD1', through, activation, of, signal, transducer, and, activator, of, transcription, '(', 'STAT)', 3])]). relacion([sujeto(['In', 'turn,', elevated, 'miR-135b']), verbo([targeted]), complemento(['FOXO1', in, 'ALCL', cells])]). relacion([sujeto(['miR-135b', introduction, also]), verbo([decreased]), complemento([chemosensitivity, in, 'Jurkat', 'cells,', suggesting, its, contribution, to, oncogenic, activities, of, 'NPM-ALK'])]). relacion([sujeto(['Interestingly,', 'miR-135b']), verbo([suppressed]), complemento(['T-helper', '(', 'Th)', 2, master, regulators, 'STAT6', and, 'GATA3,', and, 'miR-135b', blockade, attenuated, 'IL-17', production, and, paracrine, inflammatory, response, by, 'ALCL', 'cells,', indicating, that, 'miR-135b-mediated', 'Th2', suppression, may, lead, to, the, skewing, to, 'ALCL', immunophenotype, overlapping, with, 'Th17', cells])]). relacion([sujeto(['Effects', of, icariin, on, airway, inflammation, in, asthmatic, rats, and, the, intervention, of, 'LPS']), verbo([induced]), complemento([inflammation, are, interfered, with, the, machanism, of, icariin])]). relacion([sujeto(['Western', blotting, was, used, to, observe, the, icariin, intervention, effects, on, 'T-bet,', 'GATA-3', and]), verbo([nuclear]), complemento(['factor-Kappa', 'B', '(', 'NF-κB)', p65, protein, expressions, in, rat, pulmonary, tissue])]). relacion([sujeto(['The', 'ELISA', results, from, pulmonary, tissue, showed, that, 'IL-4', expression, was, significantly, reduced, '(', 'P', &, 'lt;', 0.05, ')', ',', while, the, 'IFN-γ', expression]), verbo([increased]), complemento([but, not, significantly, when, we, compared, 'OVA+icariin', medium, and, high, dose, groups, with, the, asthma, group])]). relacion([sujeto(['Immunohistochemical', staining, of, pulmonary, tissue, showed, that, the, 'GATA-3']), verbo([decreased]), complemento([significantly, while, the, 'T-bet', staining, did, not, change, in, the, 'OVA+icariin', high, dose, group])]). relacion([sujeto(['GATA-3', mRNA, expression, in, pulmonary, tissue, significantly]), verbo([decreased]), complemento(['(', 'P', &, 'lt;', 0.05, ')', while, 'T-bet', mRNA, expression, decreased, but, not, significantly, in, the, icariin, treatment, group, compared, with, the, asthma, group])]). relacion([sujeto(['T-bet', and, 'GATA-3', protein, expressions, in, pulmonary, tissue]), verbo([increased]), complemento([significantly, compared, with, the, asthma, 'group,', which, meant, that, icariin, could, inhibit, the, increase, of, 'GATA-3', 'protein,', but, not, of, 'T-bet'])]). relacion([sujeto(['The', expression, of, total, p65, protein]), verbo([decreased]), complemento([with, icariin, treatment, while, the, expression, of, cytoplasmic, p65, protein, increased])]). relacion([sujeto(['Icariin', could]), verbo([regulate]), complemento([the, imbalance, of, 'Th1/Th2', cytokines, in, asthmatic, rat, pulmonary, tissue])]). relacion([sujeto(['Icariin', could]), verbo([regulate]), complemento([the, imbalance, of, 'Th1/Th2', associated, transcription, factors, 'T-bet', and, 'GATA-3', in, asthmatic, rat, pulmonary, tissue, and, spleen, lymphocytes])]). relacion([sujeto(['Icariin', could]), verbo([inhibit]), complemento([the, activation, of, 'NF-κB', p65, protein, in, asthmatic, rat, pulmonary, tissue])]). relacion([sujeto(['We', recently]), verbo([reported]), complemento([that, 'c-Myb,', 'GATA-3,', and, 'Menin', form, a, core, transcription, complex, that, regulates, 'GATA-3', expression, and, ultimately, 'Th2', cell, development, in, human, peripheral, blood, 'T', cells])]). relacion([sujeto(['In', this, 'article,', we]), verbo([report]), complemento([that, 'c-Myb', and, 'GATA-3', cooperatively, play, an, essential, role, in, 'IL-13', expression, though, direct, binding, to, a, conserved, 'GATA-3', response, element, '(', 'CGRE),', an, enhancer, for, 'IL-13', expression])]). relacion([sujeto(['c-Myb', and, 'GATA-3', were, shown, to]), verbo([activate]), complemento([the, 'CGRE-IL-13', promoter, by, '∼160-fold,', and, mutation, of, the, canonical, 'Myb', binding, site, completely, abrogated, 'CGRE', enhancer, activity])]). relacion([sujeto(['In', 'contrast,', mutation, of, the, 'GATA']), verbo([binding]), complemento([site, partially, decreased, 'CGRE', enhancer, activity])]). relacion([sujeto(['GATA-3', did, not]), verbo([bind]), complemento([to, 'CGRE', when, 'c-myb', expression, was, silenced])]). relacion([sujeto(['c-Myb,', 'GATA-3,', 'Menin,', and, mixed, lineage, leukemia, '(', 'MLL)']), verbo([bound]), complemento([to, 'CGRE', in, human, primary, 'CD4(+)', 'effector/memory', cells])]). relacion([sujeto(['Moreover,', 'c-myb', silencing, significantly]), verbo([decreased]), complemento([both, methylation, of, histone, 'H3K4', and, acetylation, of, histone, 'H3K9', at, the, 'IL-13', locus, in, 'CD4(+)', 'effector/memory', cells])]). relacion([sujeto(['Therefore,', in, addition, to, the, strong, enhancer, effect, for, the, transcription, of, 'IL-13,', the, 'c-Myb/GATA-3', complex]), verbo([recruits]), complemento(['MLL', to, the, 'CGRE', for, histone, modification, of, the, 'IL-13', locus, during, the, differentiation, of, memory, 'Th2', cells])]). relacion([sujeto(['Recent']), verbo([reports]), complemento([have, revealed, that, 'CD4(+)', 'T(h)', cell, subsets, have, the, ability, to, alter, their, gene, expression, pattern, in, response, to, extracellular, stimuli])]). relacion([sujeto(['We', previously, highlighted, the, plasticity, of, 'T(h)1', cells, by, demonstrating, that, 'T(h)1', cells]), verbo([gain]), complemento([the, capacity, to, produce, 'IL-3,', 'IL-9,', 'IL-13', and, granulocyte, macrophage, 'colony-stimulating', factor, in, response, to, 'antigen,', 'IL-2', and, 'IL-18,', and, based, on, their, unique, 'function,', we, designated, these, activated, 'T(h)1', cells, as, '\'', super, 'T(h)1', 'cells\''])]). relacion([sujeto(['However,', the, precise, molecular, mechanism, underlying, 'IL-13', production, by, super, 'T(h)1', cells]), verbo([has]), complemento([not, been, elucidated])]). relacion([sujeto(['Here,', we, show, that, the, 'GATA-binding', protein, 3, '(', 'Gata3)', is, essentially]), verbo([required]), complemento([for, 'II13', gene, expression, in, super, 'T(h)1', cells])]). relacion([sujeto(['Gata3', is, synergistically]), verbo([induced]), complemento([in, 'T-box', expressed, in, 'T-cells', '(', 'T-bet)-expressing', 'T(h)1', cells, when, 'co-stimulated', with, 'anti-CD3,', 'IL-18', and, 'IL-4', through, the, activation, of, nuclear, factor, of, activated, 'T', 'cells,', nuclear, factor, 'kappa-light-chain-enhancer', of, activated, 'B', cells, and, signal, transducer, and, activator, of, transcription, 6, ',', respectively])]). relacion([sujeto(['However,', 'Gata3', induction, is, not, 'satisfactory,', and, additional, 'TCR', or, 'anti-CD3', signaling, is, prerequisite, for]), verbo([triggering]), complemento(['IL-13', production, by, 'Gata3', plus, 'T-bet-expressing', 'T(h)1', cells])]). relacion([sujeto(['These', findings]), verbo([suggest]), complemento([that, 'Gata3,', which, is, not, originally, expressed, in, 'T(h)1', 'cells,', alters, the, cytokine, production, profile, by, 'T(h)1', cells])]). relacion([sujeto(['Glatiramer', acetate, '(', 'GA)', treatment]), verbo([suppresses]), complemento([disease, activity, in, multiple, sclerosis, '(', 'MS)'])]). relacion([sujeto(['High', expression, of, mRNA, encoding, 'GATA3', and, 'lymphotoxin-β', '(', 'LT-β)', was]), verbo([associated]), complemento([with, low, disease, activity, in, 'Gd-enhanced', 'MRI', studies])]). relacion([sujeto(['None', of, the, variables, studied, were]), verbo([associated]), complemento([with, clinical, disease, activity])]). relacion([sujeto(['Some', 'organ-transplanted', patients, achieve, a, state, of, &, 'quot;operational', 'tolerance"', '(', 'OT)', in, which, graft, function, is]), verbo([maintained]), complemento([after, the, complete, withdrawal, of, immunosuppressive, drugs])]). relacion([sujeto(['The', significant, 'GATA3', gene, and, protein, expressions, in, 'OT', individuals]), verbo([suggest]), complemento([that, a, 'Th2', deviation, may, be, a, relevant, pathway, to, 'OT'])]). relacion([sujeto(['Moreover,', the, capacity, of, the, 'REG/INFLAMMA', gene, panel, to, discriminate, 'OT', by, peripheral, blood, analysis, indicates, that, this, state]), verbo([has]), complemento([systemic, repercussions])]). relacion([sujeto(['Follicular', 'T', helper, '(', 'Tfh)', cells]), verbo([provide]), complemento([critical, help, to, 'B', cells, for, germinal, center, '(', 'GC)', formation])]). relacion([sujeto(['Mutations', affecting, 'SLAM-associated', protein, '(', 'SAP)']), verbo([prevent]), complemento(['GC', formation, because, of, defective, 'T cell-B', cell, 'interactions,', yet, effects, on, 'Tfh', cell, differentiation, remain, unclear])]). relacion([sujeto(['We', describe, the, 'in vitro', differentiation, of, functionally, competent, &, 'quot;Tfh-like"', cells, that]), verbo([expressed]), complemento(['interleukin-21,', 'Tfh', cell, 'markers,', and, 'Bcl6', and, rescued, 'GC', formation, in, 'SAP-deficient', hosts, better, than, other, 'T', helper, '(', 'Th)', cells])]). relacion([sujeto(['It']), verbo([has]), complemento([been, indicated, that, 'T-box', 21, '(', 'TBX21)', and, 'H', 2.0, -, like, homeobox, '(', 'HLX)', are, transcription, factors, related, to, the, differentiation, of, 'T', helper, 1, 'cells,', whereas, 'GATA-binding', protein, 3, is, the, master, transcription, factor, of, 'T', helper, 2, cells])]). relacion([sujeto(['Functional', polymorphisms, in, 'TBX21', are]), verbo([associated]), complemento([with, the, development, of, autoimmune, thyroid, diseases, and, prognosis, of, 'GD,', and, a, functional, polymorphism, in, 'HLX', in, combination, with, the, 'TBX21', polymorphism, is, also, associated, with, the, prognosis, of, 'GD'])]). relacion([sujeto(['The', objective, was, to, determine, whether, 'MetS-associated', prostate, alterations, are]), verbo([prevented]), complemento([by, testosterone, supplementation])]). relacion([sujeto(['The', mRNA, expression, of, several, proinflammatory, '(', 'IL8,', 'IL6,', 'IL1β,', and, 'TNFα),', 'T', lymphocyte, '(', 'CD4,', 'CD8,', 'Tbet,', 'Gata3,', and, 'ROR', 'γt),', macrophage, '(', 'TLR2,', 'TLR4,', and, 'STAMP2),', neutrophil, '(', 'lactoferrin),', inflammation, '(', 'COX2', and, 'RAGE),', and, 'fibrosis/myofibroblast', activation, '(', 'TGFβ,', 'SM22α,', 'αSMA,', 'RhoA,', and, 'ROCK1/ROCK2)', markers, was, significantly]), verbo([increased]), complemento([in, 'HFD', prostate])]). relacion([sujeto(['Testosterone,', as, well, as, 'INT-747,', treatment]), verbo([prevented]), complemento([some, 'MetS', 'features,', although, only, testosterone, normalized, all, the, 'HFD-induced', prostate, alterations])]). relacion([sujeto(['Interestingly,', the, ratio, between, testosterone, and, estradiol, plasma, level]), verbo([retains]), complemento([a, 'significant,', 'negative,', association, with, all, the, fibrosis, and, the, majority, of, inflammatory, markers, analyzed])]). relacion([sujeto(['We']), verbo([have]), complemento([identified, 'GATA-3', cDNA, and, its, splice, variant, in, 'Atlantic', cod])]). relacion([sujeto(['Cod', 'GATA-3', '(', 'GmGATA-3)']), verbo([has]), complemento([a, 1320, b, p, open, reading, frame, encoding, a, polypeptide, of, 440, amino, acids, with, two, zinc, finger, domains, that, are, well, conserved, within, teleosts, and, higher, vertebrates])]). relacion([sujeto(['The', full, length, 'GATA-3', with, two, zinc, finger, domains]), verbo([has]), complemento([a, transcriptional, function, confirmed, by, transfection, with, 'GATA-3', reporter, vector, along, with, expression, constructs, of, 'GATA-3', plasmids, in, 'CHSE-214', 'cells,', whereas, the, 'GATA-3', splice, variant, without, zinc, finger, domain, did, not, enhance, the, activity, of, the, 'GATA-3', reporter, 'vector,', and, no, interference, was, found, between, these, two, 'GATA-3', variants])]). relacion([sujeto(['RT-PCR', analysis, revealed, that, the, two, 'Atlantic', cod, 'GATA-3', variants, were, strongly]), verbo([expressed]), complemento([in, the, gills, and, infection, with, live, 'Vibrio', anguillarum, induced, the, spleen, expression, of, both, 'GmGATA-3L', and, 'GmGATA-3S'])]). relacion([sujeto(['Unexpectedly,', 'PMA']), verbo([increased]), complemento([the, expression, of, the, 'GATA-3', splice, variant, in, vivo, and, especially, in, 'vitro,', with, an, increase, of, more, than, 100, ',', 0, -, fold, in, head, kidney, leukocytes, at, 24, and, 48, h])]). relacion([sujeto(['On', the, other, 'hand,', there, were, no, significant]), verbo([increases]), complemento([at, the, transcript, level, of, full, length, 'GATA-3', between, 'Poly', 'I:C', and, 'β-glucan', treatment, groups, compared, to, controls])]). relacion([sujeto(['To', 'date,', the, factors]), verbo([involved]), complemento([in, the, control, of, these, aspects, of, 'Treg', physiology, remain, poorly, understood])]). relacion([sujeto(['Here,', we, show, that, the, canonical, 'Th2', transcription, factor, 'GATA3', is, selectively]), verbo([expressed]), complemento([in, 'Tregs', residing, in, barrier, sites, including, the, gastrointestinal, tract, and, the, skin])]). relacion([sujeto(['GATA3', expression, in, both, murine, and, human, 'Tregs', was]), verbo([induced]), complemento([upon, 'TCR', and, 'IL-2', stimulation])]). relacion([sujeto(['Although', 'GATA3', was, not]), verbo([required]), complemento([to, sustain, 'Treg', homeostasis, and, function, at, steady, 'state,', 'GATA3', played, a, cardinal, role, in, 'Treg', physiology, during, inflammation])]). relacion([sujeto(['Indeed,', the, intrinsic, expression, of, 'GATA3', by, 'Tregs', was]), verbo([required]), complemento([for, their, ability, to, accumulate, at, inflamed, sites, and, to, maintain, high, levels, of, 'Foxp3', expression, in, various, polarized, or, inflammatory, settings])]). relacion([sujeto(['Overall,', our, work]), verbo([reveals]), complemento([what, we, believe, to, be, a, new, facet, in, the, complex, role, of, 'GATA3', in, 'T', cells, and, highlights, what, may, be, a, fundamental, role, in, controlling, 'Treg', physiology, during, inflammation])]). relacion([sujeto(['Th17', cells, are, highly, pathogenic, in, a, variety, of, 'immune-mediated', 'diseases,', and, a, thorough, understanding, of, the, mechanisms, of, 'cytokine-mediated', suppression, of, 'Th17', cells]), verbo([has]), complemento([great, therapeutic, potential])]). relacion([sujeto(['We', demonstrate, that, 'IL-4']), verbo([suppresses]), complemento([reactivation, of, committed, 'Th17', 'cells,', even, in, the, presence, of, 'TGF-β,', 'IL-6,', and, 'IL-23'])]). relacion([sujeto(['Downregulation', of, 'IL-17', by, 'IL-4', is, dependent, on, 'STAT6', and]), verbo([mediated]), complemento([by, inhibition, of, 'STAT3', binding, at, the, 'Il17a', promoter])]). relacion([sujeto(['Although', 'Th1', cytokines, were, shown, to]), verbo([induce]), complemento(['IFN-γ', expression, by, 'Th17', 'cells,', 'IL-4', does, not, induce, a, 'Th2', phenotype, in, 'Th17', cells])]). relacion([sujeto(['Suppression', by, 'IL-4', is, stable, and, 'long-lived', when, applied, to, immature, 'Th17', 'cells,', but, cells, that]), verbo([have]), complemento([undergone, multiple, rounds, of, 'stimulation,', either, in, vivo, during, a, 'Th17-mediated', inflammatory, 'disease,', or, in, 'vitro,', become, resistant, to, suppression, by, 'IL-4', and, lose, the, ability, to, signal, through, 'IL-4R'])]). relacion([sujeto(['The', transcription, factors, 'E2A,', 'GATA-binding', protein, 3, '(', 'Gata3)', and, 'RUNT-related', transcription, factor, '(', 'Runx)', are]), verbo([involved]), complemento([at, various, stages, in, the, differentiation, of, 'double-negative', thymocytes, and, in, 'β-selection,', as, are, transcription, factors, from, the, 'Notch', signaling, 'pathway;', other, transcription, factors, such, as, 'B-cell', 'lymphoma/leukemia', 11, b, '(', 'Bcl11b),', myeloblastosis, viral, oncogene, homolog, '(', 'Myb)', and, inhibitor, of, 'DNA', binding, 3, '(', 'Id3)', are, involved, at, specific, stages])]). relacion([sujeto(['Differentiation', of, 'T', cells, into, helper, versus, cytotoxic, cells]), verbo([involves]), complemento([not, only, antagonistic, interplay, between, 'Runx', and, 'T(h)', inducing, 'POZ-Kruppel', factor, '(', 'ThPOK)', but, also, complex, interactions, between, 'MAZR,', 'Gata3', and, 'Myb', in, the, activation, and, silencing, of, genes, such, as, 'Cd4', and, 'Cd8', as, well, as, the, gene, that, encodes, 'ThPOK', itself])]). relacion([sujeto(['A', wide, range, of, 'well-defined', transcription, 'factors,', including, signal, transducer, and, activator, of, transcriptions, '(', 'STATs),', 'T-bet,', 'Gata3,']), verbo([nuclear]), complemento([factor, of, activated, 'T', cell, '(', 'NFAT),', 'adaptor-related', protein, complex, 1, '(', 'AP-1)', and, nuclear, factor, κB, '(', 'NF-κB),', are, known, to, shape, 'T(h)1/T(h)2', differentiation])]). relacion([sujeto(['Runx', and, 'Gata3', also, operate, in, this, 'process,', as, do, 'c-Maf', and, recombining]), verbo([binding]), complemento([protein, for, immunoglobulin, 'Jκ', region, '(', 'RBP-J)', and, the, 'chromatin-reorganizing', protein, special, 'AT-rich', 'sequence-binding', protein, 1, '(', 'SATB1)'])]). relacion([sujeto(['We']), verbo([have]), complemento([previously, reported, that, transgenic, overexpression, of, 'CD200', in, either, mouse, skin, graft, donors, or, recipients, significantly, enhances, skin, allograft, survival])]). relacion([sujeto(['By', focused, microarray, analysis, we, showed, this]), verbo([enhanced]), complemento([graft, survival, is, associated, with, increased, expression, of, 'Foxp3,', 'GITR,', 'CTLA-4', and, 'CCR4', 'mRNA,', all, genes, related, to, 'T(reg)', cell, 'induction/function,', and, of, 'Gata3,', 'IL-4,', 'IL-5,', 'IL-13,', and, somewhat, 'surprisingly,', of, 'T-bet,', 'INF-γ', and, granzyme, b])]). relacion([sujeto(['Gene-specific', 'real-time', 'PCR', and, immunohistochemistry, analysis, confirmed, an]), verbo([increase]), complemento([in, 'Foxp3(+)', 'T(reg)', cells, in, both, the, skin, grafts, and, draining, lymph, nodes, '(', 'DLNs)', of, 'CD200(tg)', recipient, mice, at, both, 7, /, 14, days, post, 'engraftment,', as, well, as, providing, evidence, for, increased, expression, of, the, ligands, for, 'CCR4,', 'CCL17', and, 'CCL22', in, both, locations])]). relacion([sujeto(['Following', 'lentivirus-mediated', shRNA, treatment, of, 'Dox-treated', 'CD200(tg)', mice, to, attenuate, expression, of, 'CCR4', 'mRNA,', the]), verbo([increased]), complemento([localization, of, 'T(reg)', cells, in, 'skin/DLN', of, 'CD200(tg)', recipients, was, 'abolished,', and, the, enhanced, graft, survival, similarly, reversed])]). relacion([sujeto(['We', conclude, that]), verbo([enhanced]), complemento(['CCR4', dependent, migration, of, 'Foxp3(+)', 'T(reg)', to, grafted, tissue, and, 'DLNs', is, an, essential, step, in, the, graft, prolongation, afforded, by, overexpression, of, 'CD200'])]). relacion([sujeto(['Furthermore,', these]), verbo([increased]), complemento([levels, correlate, with, poorer, survival, of, cancer, 'patients,', suggesting, that, serum, levels, of, 'YKL-40', might, be, a, prognostic, biomarker])]). relacion([sujeto(['Breast', ductal, carcinoma, in, situ]), verbo([expressed]), complemento([low, and, moderate, levels, of, 'YKL-40'])]). relacion([sujeto(['These', data, demonstrate, that, expression, levels, of, 'YKL-40', are]), verbo([associated]), complemento([with, tumour, 'grade,', poor, 'differentiation,', and, other, breast, cancer, 'markers,', highlighting, that, tissue, levels, of, 'YKL-40', serve, as, a, valuable, biomarker, for, breast, cancer, diagnosis, and, prognosis])]). relacion([sujeto(['Parental,', particularly, 'maternal,', smoking]), verbo([increases]), complemento([the, risk, for, childhood, allergic, asthma, and, infection])]). relacion([sujeto(['Prenatal,', but, not, 'postnatal,', 'SS', strongly]), verbo([increased]), complemento([methacholine, and, allergen, '(', 'Aspergillus)-induced', airway, 'resistance,', 'Th2', cytokine, 'levels,', and, atopy, and, activated, the, 'Th2-polarizing', pathway, 'GATA3/Lck/ERK1/2/STAT6'])]). relacion([sujeto(['Given', that, 'SS/nicotine', exposure, of, normal, adult, mice]), verbo([promotes]), complemento([mucus, 'formation,', the, results, suggested, that, fetal, and, neonatal, lung, are, highly, sensitive, to, cigarette, smoke])]). relacion([sujeto(['Thus,', although, the, gestational, 'SS']), verbo([promotes]), complemento(['Th2', 'polarization/allergic', 'asthma,', it, may, also, impair, 'and/or', delay, the, development, of, fetal, and, neonatal, 'lung,', affecting, mucociliary, clearance, and, 'Th1', responses])]). relacion([sujeto(['Together,', this, may, explain, the]), verbo([increased]), complemento([susceptibility, of, children, from, smoking, parents, to, allergic, asthma, and, childhood, respiratory, infections])]). relacion([sujeto(['Here', we]), verbo([have]), complemento([explored, a, role, for, 'Gata-3', in, tumor, initiation, and, the, underlying, cellular, mechanisms, using, a, mouse, model, of, &, 'quot;luminal-like"', cancer])]). relacion([sujeto(['Through', the, identification, of, two, distinct, luminal, progenitor, cells, in, the, mammary, 'gland,', we, demonstrate, that, 'Gata-3', 'haplo-insufficiency']), verbo([increases]), complemento([the, 'tumor-initiating', capacity, of, these, progenitors, but, not, the, stem, 'cell-enriched', population])]). relacion([sujeto(['Overexpression', of, a, conditional, 'Gata-3', transgene, in, the, 'PyMT', model]), verbo([promoted]), complemento([cellular, differentiation, and, led, to, reduced, 'tumor-initiating', capacity, as, well, as, diminished, angiogenesis])]). relacion([sujeto(['Transcript', profiling, studies, identified, 'caspase-14', as, a, novel, downstream]), verbo([target]), complemento([of, 'Gata-3,', in, keeping, with, its, roles, in, differentiation, and, tumorigenesis])]). relacion([sujeto(['Overall,', these, studies, identify, 'GATA-3', as, an, important, regulator, of, tumor, initiation, through, its, ability, to]), verbo([promote]), complemento([the, differentiation, of, committed, luminal, progenitor, cells])]). relacion([sujeto(['Forkhead', 'Box', 'P3', '(', 'Foxp3)-expressing', regulatory, 'T', '(', 'Treg)', cells, are, central, to]), verbo([maintaining]), complemento(['self-tolerance', and, immune, homeostasis])]). relacion([sujeto(['How', 'Treg', cell, function, and, 'Foxp3', expression, are]), verbo([regulated]), complemento([is, an, important, question, under, intensive, investigation])]). relacion([sujeto(['Here,', we]), verbo([have]), complemento([demonstrated, an, essential, role, for, the, transcription, factor, 'GATA-3,', a, previously, recognized, 'Th2', cell, master, 'regulator,', in, controlling, 'Treg', cell, function])]). relacion([sujeto(['Treg', 'cell-specific', 'GATA-3', deletion]), verbo([led]), complemento(['to a', spontaneous, inflammatory, disorder, in, mice])]). relacion([sujeto(['GATA-3-null', 'Treg', cells, were, defective, in, peripheral, homeostasis, and, suppressive, 'function,', gained, 'Th17', cell, 'phenotypes,', and]), verbo([expressed]), complemento([reduced, amounts, of, 'Foxp3'])]). relacion([sujeto(['In', 'addition,', 'GATA-3', controlled, 'Foxp3', expression, by]), verbo([binding]), complemento([to, and, promoting, the, activity, of, 'cis-acting', elements, of, 'Foxp3'])]). relacion([sujeto(['These', findings]), verbo([provide]), complemento([insights, into, immune, regulatory, mechanisms, and, uncover, a, critical, function, of, 'GATA-3', in, 'Treg', cells, and, immune, tolerance])]). relacion([sujeto(['Although', recent]), verbo([reports]), complemento([suggest, a, possible, role, for, an, imbalance, in, 'Th1', and, 'Th2', proinflammatory, cytokines, in, the, development, and, progression, of, 'glomerulonephritis,', there, is, little, information, on, 'Th1', or, 'Th2', predominance, in, 'Henoch-Schönlein', purpura, nephritis, '(', 'HSPN)'])]). relacion([sujeto(['Since', 'T-bet', and, 'GATA-3', are, transcriptional, factors, that]), verbo([regulate]), complemento([the, differentiation, of, helper, 'T', lymphocytes, into, 'Th1', and, 'Th2,', we, examined, the, relative, mRNA, expression, of, 'T-bet', and, 'GATA-3', in, the, urinary, sediment, of, children, with, proteinuric, 'HSPN', by, 'real-time', quantitative, 'PCR'])]). relacion([sujeto(['Moreover,', a, significantly]), verbo([increased]), complemento([intensity, of, 'T-bet', immunostaining, was, observed, in, the, glomeruli, in, the, biopsy, specimen, of, all, study, patients])]). relacion([sujeto(['Repeat', measurements, of, urinary, mRNA, expression, of, 'T-bet', and, 'GATA-3', after, treatment, revealed, that, the, expression, of, 'T-bet', in, patients, had, significantly]), verbo([decreased]), complemento([relative, to, the, baseline, '(', p, =, 0.003, ')', ',', while, the, expression, of, 'GATA-3', remained, static])]). relacion([sujeto(['In', a, patient, subjected, to, a, 'post-treatment', renal, 'biopsy,', the]), verbo([increased]), complemento([intensity, of, immunostaining, of, 'T-bet', had, clearly, diminished, following, immunosuppressive, 'treatment,', in, accordance, with, a, significant, decrease, in, urinary, mRNA, expression, of, 'T-bet'])]). relacion([sujeto(['These', observations]), verbo([suggest]), complemento([that, patients, with, proteinuric, 'HSPN', demonstrate, increased, 'T-bet', and, depressed, 'GATA-3', expression, in, the, urinary, 'sediment,', indicating, a, possible, shift, in, 'Th1/Th2', balance, towards, 'Th1', predominance])]). relacion([sujeto(['Discovery', of, mechanisms, that, impede, the, aggressive, and, metastatic, phenotype, of, human, basal, 'triple-negative-type', breast, cancers, '(', 'BTNBCs)', could]), verbo([provide]), complemento([novel, targets, for, therapy, for, this, form, of, breast, cancer, that, has, a, relatively, poor, prognosis])]). relacion([sujeto(['Previous', studies]), verbo([have]), complemento([demonstrated, that, expression, of, 'GATA3,', the, master, transcriptional, regulator, of, mammary, luminal, 'differentiation,', can, reduce, the, tumorigenicity, and, metastatic, propensity, of, the, human, 'BTNBC', 'MDA-MB-231', cell, line, '(', 'MB231),', although, the, mechanism, for, reduced, metastases, was, not, elucidated])]). relacion([sujeto(['Conversely,', reduction, of, 'GATA3', expression, by, small, interfering, 'RNA', in, luminal, 'BT474', cells]), verbo([increased]), complemento(['LOX', expression])]). relacion([sujeto(['Similarly,', human, breast, cancer, microarray, data, demonstrated, that, high, 'LOX/low', 'GATA3', expression, is]), verbo([associated]), complemento([with, the, 'BTNBC', subtype, of, breast, cancer, and, poor, patient, prognosis])]). relacion([sujeto(['Expression', of, 'GATA3', reprograms, 'BTNBCs', to, a, less, aggressive, phenotype, and]), verbo([inhibits]), complemento([a, major, mechanism, of, metastasis, through, inhibition, of, 'LOX'])]). relacion([sujeto(['Induction', of, 'GATA3', in, 'BTNBC', cells, or, novel, approaches, that]), verbo([inhibit]), complemento(['LOX', expression, or, activity, could, be, important, strategies, for, treating, 'BTNBCs'])]). relacion([sujeto(['Despite', the, role, of, the, estrogen, receptor, α, '(', 'ERα)', pathway, as, a, key, growth, driver, for, breast, 'cells,', the, phenotypic, consequence, of, exogenous, introduction, of, 'ERα', into, 'ERα-negative', cells, paradoxically]), verbo([has]), complemento([been, growth, inhibition])]). relacion([sujeto(['We', mapped, the]), verbo([binding]), complemento([profiles, of, 'ERα', and, its, interacting, transcription, factors, '(', 'TFs),', 'FOXA1', and, 'GATA3', in, 'MCF-7', breast, carcinoma, 'cells,', and, observed, that, these, three, 'TFs', form, a, functional, enhanceosome, that, regulates, the, genes, driving, core, 'ERα', function, and, cooperatively, modulate, the, transcriptional, networks, previously, ascribed, to, 'ERα', alone])]). relacion([sujeto(['We', demonstrate, that, these, enhanceosome, occupied, sites, are]), verbo([associated]), complemento([with, optimal, enhancer, characteristics, with, highest, p300, 'co-activator', 'recruitment,', 'RNA', 'Pol', 'II', 'occupancy,', and, chromatin, opening])]). relacion([sujeto(['Cumulatively,', these, results]), verbo([suggest]), complemento([that, all, the, enhanceosome, components, comprising, 'ERα,', 'FOXA1,', and, 'GATA3', are, necessary, for, the, full, repertoire, of, 'cancer-associated', effects, of, the, 'ERα'])]). relacion([sujeto(['Beta-arrestin', 2]), verbo([has]), complemento([been, shown, to, participate, in, the, pathogenesis, of, asthma, by, inducing, 'Th2', cell, migration, to, the, lungs])]). relacion([sujeto(['Whether', 'beta-arrestin', 2]), verbo([regulates]), complemento([cytokine, production, of, 'CD4+', 'T', cells, is, still, unknown])]). relacion([sujeto(['The', aim, of, the, present, study, was, to, investigate, the, effect, of, 'beta-arrestin', 2, on, the, cytokine, production, of, 'CD4+', 'T', lymphocytes, and, the, mechanism]), verbo([involved]), complemento([in, a, mouse, model, for, asthma])]). relacion([sujeto(['CD4+', 'T', lymphocytes, of, mice, with, allergic, asthma]), verbo([expressed]), complemento([higher, levels, of, 'beta-arrestin', 2, on, both, mRNA, and, protein, levels])]). relacion([sujeto(['beta-arrestin', 2, 'RNAi']), verbo([decreased]), complemento(['IL-4', '(', 43.16, '%', ')', and, 'GATA3', '(', protein, 77.21, '%', ',', mRNA, 62.98, '%', ')', expression, after, terbutaline, stimulation])]). relacion([sujeto(['Cell-surface', beta2AR, of, 'CD4+', 'T', lymphocytes]), verbo([decreased]), complemento(['(', 15.27, '%', ')', after, terbutaline, 'treatment,', but, recovered, after, 'beta-arrestin', 2, 'RNAi', 'down-modulation'])]). relacion([sujeto(['These', findings, demonstrate, that, 'beta-arrestin', 2]), verbo([regulates]), complemento(['IL-4', production, and, 'GATA3', expression, of, 'CD4+', 'T', lymphocytes, partly, through, the, beta2AR, signaling, pathway, in, an, allergic, asthma, model])]). relacion([sujeto(['To', understand, 'GATA3-mediated', gene, 'regulation,', we, identified, 'genome-wide', 'GATA3']), verbo([binding]), complemento([sites, in, ten, 'well-defined', developmental, and, effector, 'T', lymphocyte, lineages])]). relacion([sujeto(['In', the, 'thymus,', 'GATA3', directly]), verbo([regulated]), complemento([many, critical, 'factors,', including, 'Th-POK,', 'Notch1,', and, 'T cell', receptor, subunits])]). relacion([sujeto(['In', the, 'periphery,', 'GATA3']), verbo([induced]), complemento([a, large, number, of, 'Th2', 'cell-specific', as, well, as, 'Th2', 'cell-nonspecific', 'genes,', including, several, transcription, factors])]). relacion([sujeto(['Our', data, also, indicate, that, 'GATA3']), verbo([regulates]), complemento([both, active, and, repressive, histone, modifications, of, many, target, genes, at, their, regulatory, elements, near, 'GATA3', binding, sites])]). relacion([sujeto(['Overall,', although, 'GATA3']), verbo([binding]), complemento([exhibited, both, shared, and, 'cell-specific', patterns, among, various, 'T cell', 'lineages,', many, genes, were, either, positively, or, negatively, regulated, by, 'GATA3', in, a, cell, 'type-specific', 'manner,', suggesting, that, 'GATA3-mediated', gene, regulation, depends, strongly, on, cofactors, existing, in, different, 'T cells'])]). relacion([sujeto(['HIV', coinfection, modifies, the, clinical, course, of, leishmaniasis, by]), verbo([promoting]), complemento([a, 'Th2', pattern, of, cytokine, production])]). relacion([sujeto(['Leishmania', braziliensis, antigens]), verbo([induced]), complemento(['CD69', expression, on, 'CD3+CD4+', and, 'CD3+CD8+', cells])]). relacion([sujeto(['It', also]), verbo([increased]), complemento(['IL-4', intracellular, staining, on, 'CD3+CD4+GATA3-', population, and, decreased, the, percentage, of, 'CD3+CD4+IL-17+', cells])]). relacion([sujeto(['This']), verbo([suggests]), complemento([that, modulations, in, the, 'IL-4R/STAT6', pathway, and, the, 'Th17', population, may, serve, as, parasitic, evasion, mechanisms, in, 'HIV/ML'])]). relacion([sujeto(['Further', studies, are]), verbo([required]), complemento([to, confirm, these, results])]). relacion([sujeto(['The', effects, of, 'T', helper, '(', 'Th)', cells, on, alcoholic, cardiomyopathy]), verbo([have]), complemento([not, been, extensively, investigated])]). relacion([sujeto(['Alcohol', consumption]), verbo([caused]), complemento([a, decrease, in, the, 'Th1', polarization, and, an, increase, in, the, 'Th2', response])]). relacion([sujeto(['Chronic', alcohol, consumption]), verbo([induced]), complemento([a, 'Th2', response, within, the, 'Th1/Th2', balance])]). relacion([sujeto(['Th2', response, is, one, of, the, underlying, mechanism]), verbo([involved]), complemento([in, 'alcohol-induced', cardiac, fibrosis])]). relacion([sujeto(['While', many, cancer, cells, depend, on, exogenous, glutamine, for, survival, to, justify, the, therapeutic]), verbo([targeting]), complemento([of, glutamine, 'metabolism,', the, mechanisms, of, glutamine, dependence, and, likely, response, and, resistance, of, such, 'glutamine-targeting', strategies, among, cancers, are, largely, unknown])]). relacion([sujeto(['In', this, 'study,', we]), verbo([have]), complemento([found, a, systematic, variation, in, the, glutamine, dependence, among, breast, tumor, subtypes, associated, with, mammary, 'differentiation:', 'basal-', but, not, 'luminal-type', breast, cells, are, more, 'glutamine-dependent', and, may, be, susceptible, to, 'glutamine-targeting', therapeutics])]). relacion([sujeto(['Glutamine', independence, of, 'luminal-type', cells, is]), verbo([associated]), complemento([mechanistically, with, 'lineage-specific', expression, of, glutamine, synthetase, '(', 'GS)'])]). relacion([sujeto(['The', 'luminal-specific', expression, of, 'GS', is, directly]), verbo([induced]), complemento([by, 'GATA3', and, represses, glutaminase, expression])]). relacion([sujeto(['In', 'addition,', the, ability, of, 'GS', to, predict, patterns, of, glutamine, metabolism, and, dependency, among, tumors, is, also, crucial, in, the, rational, design, and, application, of, glutamine, and, other, metabolic, pathway]), verbo([targeted]), complemento([therapies])]). relacion([sujeto(['The', aims, were, to, clarify, the, effect, of, placental, trophoblasts, on, 'T', lymphocytes, by, assessing, production, of, cytokines, and, expression, of, transcription, factors]), verbo([regulating]), complemento(['Th1,', 'Th2,', and, 'Th17', immunity, in, 'T', lymphocytes])]). relacion([sujeto(['We']), verbo([found]), complemento([that, the, level, of, 'IL-2,', 'IFN-γ,', 'TNF-α,', and, 'IL-17', was, significantly, decreased, when, 'T', lymphocytes, were, cultured, in, conditioned, medium, compared, with, 'control,', while, 'IL-10', and, 'IL-4', level, were, not, significantly, changed])]). relacion([sujeto(['The', presence, of, conditioned, medium, significantly]), verbo([decreased]), complemento([the, ratio, of, 'Th1/Th2'])]). relacion([sujeto(['The', expression, of, 'GATA-3', and, 'STAT-6', were, significantly]), verbo([increased]), complemento([and, 'STAT-4', was, reduced, when, 'T', lymphocyte, was, cultured, in, conditioned, 'medium,', while, the, expression, of, 'T-bet', and, 'RORC', was, not, significantly, different])]). relacion([sujeto(['We', concluded, that, placental, 'trophoblast-induced', shift, of, 'Th1/Th2', balance, toward, 'Th2', and, inhibition, of, 'Th17', might, be, among, the, mechanisms]), verbo([involved]), complemento([in, maternal, tolerance, to, fetus])]). relacion([sujeto(['The', number, of, eosinophils, and, 'CD4-positive', lymphocytes]), verbo([increased]), complemento([significantly, in, the, allergy, group, compared, with, the, control, group, '(', 'P < 0'])]). relacion([sujeto(['GATA-3', messenger, 'RNA', '(', 'mRNA)', in, the, conjunctiva, was]), verbo([expressed]), complemento([in, the, three, 'groups,', but, 'T-bet', and, 'Foxp3', were, not, detected])]). relacion([sujeto(['The', vertebrate, thymus]), verbo([provides]), complemento([an, inductive, environment, for, 'T-cell', development])]). relacion([sujeto(['TCF-1', is, highly]), verbo([expressed]), complemento([in, the, earliest, thymic, 'progenitors,', and, its, expression, is, upregulated, by, 'Notch', signals])]). relacion([sujeto(['Most', 'importantly,', when, 'TCF-1', is, forcibly]), verbo([expressed]), complemento([in, bone, marrow, '(', 'BM)', 'progenitors,', it, drives, the, development, of, 'T-lineage', cells, in, the, absence, of, 'T-inductive', 'Notch1', signals])]). relacion([sujeto(['Our', data]), verbo([suggest]), complemento([a, model, where, 'Notch', signals, induce, 'TCF-1,', and, 'TCF-1', in, turn, imprints, the, 'T-cell', fate, by, upregulating, expression, of, 'T-cell', essential, genes])]). relacion([sujeto(['We', used]), verbo([activated]), complemento(['EL-4', murine, 'T-lymphoma', 'cells,', which, produce, interleukin, '(', 'IL)-4', and, 'IL-5,', but, not, interferon, '(', 'IFN)-γ,', as, 'T(H)2', 'cell-like', cells, and, treated, them, with, 'PMA+cAMP', to, investigate, the, effects, of, shikonin, on, 'T(H)2', 'cytokines,', transcriptional, 'factors,', and, the, related, 'mitogen-activated', protein, kinase, '(', 'MAPK)/nuclear', factor, '(', 'NF)-κB', signaling, pathway])]). relacion([sujeto(['The', data, show, that, shikonin]), verbo([inhibited]), complemento([the, 'PMA+cAMP-induced', mRNA, and, protein, expression, of, 'IL-4', and, 'IL-5', via, the, downregulation, of, 'GATA-binding', 'protein-3', '(', 'GATA-3)', and, 'c-musculoaponeurotic', fibrosarcoma, '(', 'Maf)', but, not, 'T-box', expressed, in, 'T', cells, '(', 'T-bet)'])]). relacion([sujeto(['Moreover,', shikonin]), verbo([suppressed]), complemento([the, phosphorylation, of, 'p38,', inhibitor, of, κB, '(', 'IκB)', kinase, '(', 'IKK)-β', and, 'IκB-α,', and, the, subsequent, 'IκB-α', degradation, induced, by, 'PMA+cAMP;', 'however,', the, 'PMA+cAMP-induced', phosphorylation, of, extracellular, 'signal-related', kinase, '(', 'ERK),', which, resulted, in, minor, inhibition, and, phosphorylation, of, 'c-Jun', 'N-terminal', kinase, '(', 'JNK),', seemed, to, be, unaffected, by, shikonin, treatment])]). relacion([sujeto(['This', study]), verbo([suggests]), complemento([that, downregulation, of, 'GATA-3', and, 'c-Maf', via, the, suppression, of, 'p38,', 'IKK-β', and, 'IκB-α', phosphorylation, might, contribute, to, the, inhibitory, effect, of, shikonin, on, 'mitogen-induced', 'IL-4', and, 'IL-5', production, in, 'EL-4T', cells])]). relacion([sujeto(['The', expression, of, 'T-bet', mRNA]), verbo([has]), complemento([negative, correlation, with, 'GATA-3', mRNA, '(', 'r=-0'])]). relacion([sujeto([696, ')', ',', the, expression, of, 'STAT-3', mRNA]), verbo([has]), complemento([correlation, with, 'T-bet', mRNA, and, 'GATA-3', 'mRNA(r=-0'])]). relacion([sujeto(['Hyssopus', officinalis, 'L', probably]), verbo([regulates]), complemento([the, differentiation, of, 'Th1,', 'Th2', and, 'Th17', on, transcription, level, to, play, the, role, of, 'anti-inflammatory'])]). relacion([sujeto(['Gene', ontology, analysis, confirmed, enriched, expression, of, genes]), verbo([associated]), complemento([with, gene, regulation, and, neurite, outgrowth, at, early, 'stages,', with, the, 'SG', and, 'VG', often, expressing, different, members, of, the, same, gene, family])]). relacion([sujeto(['At', later, 'stages,', the, neurons]), verbo([transcribe]), complemento([more, genes, related, to, mature, 'function,', and, exhibit, a, dramatic, increase, in, immune, gene, expression])]). relacion([sujeto(['Comparisons', of, the, two, populations, revealed]), verbo([enhanced]), complemento([expression, of, 'TGFβ', pathway, components, in, 'SG', neurons, and, established, new, markers, that, consistently, distinguish, auditory, and, vestibular, neurons])]). relacion([sujeto(['Unexpectedly,', we]), verbo([found]), complemento([that, 'Gata3,', a, transcription, factor, commonly, associated, with, auditory, 'development,', is, also, expressed, in, 'VG', neurons, at, early, stages])]). relacion([sujeto(['We', therefore, defined, new, cohorts, of, transcription, factors, and, axon, guidance, molecules, that, are, uniquely]), verbo([expressed]), complemento([in, 'SG', neurons, and, may, drive, 'auditory-specific', aspects, of, their, differentiation, and, wiring])]). relacion([sujeto(['We', show, that, one, of, these, 'molecules,', the, receptor, guanylyl, cyclase, 'Npr2,', is]), verbo([required]), complemento([for, bifurcation, of, the, 'SG', central, axon])]). relacion([sujeto(['Hence,', our, dataset]), verbo([provides]), complemento([a, useful, resource, for, uncovering, the, molecular, basis, of, specific, auditory, circuit, assembly, events])]). relacion([sujeto(['TH1', 'cells,', 'TH2', 'cells,', 'IFN-γ', and, 'IL-4', levels, were, significantly]), verbo([increased]), complemento([after, 'PMA', and, ionomycin, stimulation])]). relacion([sujeto(['Ketamine', and, 'MK-801']), verbo([decreased]), complemento(['TH1', 'cells,', 'TH2', 'cells,', 'IFN-γ', and, 'IL-4', levels, but, increased, the, ratio, of, 'TH1/TH2', and, 'IFN-γ/IL-4', in, the, presence, of, 'PMA', and, ionomycin])]). relacion([sujeto(['T-bet', and, 'GATA3', activities, in, 'PBMC', were, significantly]), verbo([increased]), complemento([after, 'PMA', and, ionomycin, stimulation])]). relacion([sujeto(['Ketamine', and, 'MK-801']), verbo([decreased]), complemento(['T-bet', and, 'GATA3', activities, but, increased, the, ratio, of, 'T-bet/GATA3', following, 'PMA', and, ionomycin, stimulation])]). relacion([sujeto(['NMDA', antagonist, can]), verbo([suppress]), complemento(['TH', cell, differentiation, and, subsequent, cytokines, production, but, increase, 'TH1/TH2', ratio, following, 'PMA', and, ionomycin, 'stimulation,', it, may, be, related, to, its, regulation, on, 'T-bet', and, 'GATA3', activities])]). relacion([sujeto(['It']), verbo([has]), complemento([been, almost, a, quarter, century, since, it, was, first, appreciated, that, a, class, of, oncogenes, contained, in, rapidly, transforming, avian, retroviruses, encoded, 'DNA-binding', transcription, factors])]). relacion([sujeto(['As', with, other, 'oncogenes,', genetic, recombination, with, the, viral, genome]), verbo([led]), complemento([to, their, overexpression, or, functional, alteration])]). relacion([sujeto(['In', the, years, that, 'followed,', alterations, of, numerous, transcription, factors, were, shown, to, be, causatively]), verbo([involved]), complemento([in, various, cancers, in, human, patients, and, model, organisms])]). relacion([sujeto(['GATA', factors, are, zinc, finger, 'DNA']), verbo([binding]), complemento([proteins, that, control, the, development, of, diverse, tissues, by, activating, or, repressing, transcription])]). relacion([sujeto(['GATA', factors, thus, coordinate, cellular, maturation, with, proliferation]), verbo([arrest]), complemento([and, cell, survival])]). relacion([sujeto(['Prominent', examples, include, structural, mutations, in, 'GATA1', that, are]), verbo([found]), complemento([in, almost, all, megakaryoblastic, leukemias, in, patients, with, 'Down', 'syndrome;', loss, of, 'GATA3', expression, in, 'aggressive,', dedifferentiated, breast, 'cancers;', and, silencing, of, 'GATA4', and, 'GATA5', expression, in, colorectal, and, lung, cancers])]). relacion([sujeto(['Bile', was, collected, for, biochemical, 'analysis,', and, the, histological, changes]), verbo([associated]), complemento([with, bile, duct, injury, were, evaluated])]). relacion([sujeto(['The', expression, of, 'Muc1,', 'Muc3A,', and, 'Muc4', but, not, 'Muc2', and, 'Muc6', at, mRNA, level, in, graft, bile, ducts]), verbo([decreased]), complemento([remarkably, early, after, 'OLT'])]). relacion([sujeto(['The']), verbo([decreased]), complemento([expression, of, 'Muc1', and, 'Muc4', was, further, confirmed, at, protein, level, by, immunohistochemistry, and, immunoblotting])]). relacion([sujeto(['Downregulation', of, 'Muc1', and, 'Muc3A', expression, by, prolonged, cold, ischemic, time, was, significantly]), verbo([associated]), complemento([with, the, injury, severity, scores, of, large, but, not, small, bile, ducts])]). relacion([sujeto(['Among', six, 'GATA', 'factors,', 'GATA3,', 'GATA4,', and, 'GATA6', mRNA, were]), verbo([expressed]), complemento([in, normal, bile, ducts])]). relacion([sujeto(['GATA4', and, 'GATA6', mRNA, levels]), verbo([decreased]), complemento([significantly, after, 'OLT'])]). relacion([sujeto(['Neonatal', lung, 'GATA-3-producing', cells, were, identified, as, 'CD3(+),', 'CD4', and, 'CD8', 'double-negative', 'T', 'lymphocytes,', a, subset]), verbo([found]), complemento([at, a, higher, frequency, in, neonatal, than, adult, lung])]). relacion([sujeto(['Yet,', when]), verbo([stimulated]), complemento([in, vivo, by, 'BCG,', neonatal, lung, 'DCs', matured, and, primed, adult, naïve, 'CD4(+)', 'T', cells, toward, 'Th1', as, efficiently, as, adult, 'BCG-primed', lung, 'DCs'])]). relacion([sujeto(['Conversely,', both, adult, and, neonatal, 'BCG-primed', lung, 'DCs']), verbo([induced]), complemento([a, 'Th2', cytokine, response, from, neonatal, naïve, lymph, node, 'T', 'cells,', suggestive, of, an, intrinsic, feature, of, neonatal, 'T', lymphocytes])]). relacion([sujeto(['Antipsychotic', drugs, '(', 'APDs)', are, commonly, used, to, ease, the, symptoms, of, 'schizophrenia;', 'however,', these, same, drugs, also]), verbo([have]), complemento([an, effect, on, the, human, immune, system])]). relacion([sujeto(['Our', previous, studies]), verbo([have]), complemento([shown, that, risperidone, and, clozapine, effectively, decrease, the, production, of, 'IFN-γ', for, 'CD4(+)', 'T-cells', in, 'PBMC'])]). relacion([sujeto(['In', 'contrast,', haloperidol]), verbo([causes]), complemento([an, increase, in, the, production, of, 'IFN-γ', for, 'CD4(+)', 'T-cells', in, 'PBMC'])]). relacion([sujeto(['The', differentiation, of, 'Th1', cells, was, reduced, in, clozapine, or, risperidone, treated, 'PBMC', by]), verbo([inhibiting]), complemento([the, phosphorylation, of, 'AKT', but, not, 'STAT-4'])]). relacion([sujeto(['Typical', 'APD,', 'haloperidol,', had, the, opposite, effect, in]), verbo([regulating]), complemento(['T', cell, differentiation, when, compared, with, atypical, 'APDs', including, risperidone, and, clozapine])]). relacion([sujeto(['Haloperidol']), verbo([decreased]), complemento([the, expression, of, 'GATA-3,', a, 'Th2-related', transcription, 'factor,', by, inhibiting, 'NF-κB', activation, rather, than, 'STAT-6', phosphorylation, and, thus, decreased, 'Th2', differentiation])]). relacion([sujeto(['In', 'conclusion,', this, study]), verbo([suggests]), complemento([that, 'APDs', do, indeed, regulate, the, 'body\'s', immune, response, and, therefore, all, 'APDs', should, have, their, own, patent, in, regulating, immune, responses])]). relacion([sujeto(['The', trophoblast, cell, lineage, is, specified, early, at, the, blastocyst, 'stage,']), verbo([leading]), complemento([to, the, emergence, of, the, trophectoderm, and, the, pluripotent, cells, of, the, inner, cell, mass])]). relacion([sujeto(['Using', a, double, mRNA, amplification, technique, and, a, comparison, with, transcriptome, data, on, pluripotent, stem, 'cells,', 'placenta,', germinal, and, adult, 'tissues,', we]), verbo([report]), complemento([here, some, essential, molecular, features, of, the, human, mural, trophectoderm])]). relacion([sujeto(['In', addition, to, genes, known, for, their, role, in, placenta, '(', 'CGA,', 'PGF,', 'ALPPL2', and, 'ABCG2),', human, trophectoderm, also, strongly]), verbo([expressed]), complemento(['Laminins,', such, as, 'LAMA1,', and, the, 'GAGE', 'Cancer/Testis', genes])]). relacion([sujeto(['The', very, high, level, of, 'ABCG2', expression, in, 'trophectoderm,', 7.9, -, fold, higher, than, in, 'placenta,']), verbo([suggests]), complemento([a, major, role, of, this, gene, in, shielding, the, very, early, embryo, from, xenobiotics])]). relacion([sujeto(['A', trophectoderm, core, transcriptional, regulatory, circuitry, formed, by, 13, tightly, interconnected, transcription, factors, '(', 'CEBPA,', 'GATA2,', 'GATA3,', 'GCM1,', 'KLF5,', 'MAFK,', 'MSX2,', 'MXD1,', 'PPARD,', 'PPARG,', 'PPP1R13L,', 'TFAP2C', and, 'TP63),', was]), verbo([found]), complemento([to, be, induced, in, trophectoderm, and, maintained, in, placenta])]). relacion([sujeto(['Determining', the, mechanisms, by, which, 'T', helper, cell, 'lineage-defining', transcription, factors, are]), verbo([expressed]), complemento([and, subsequently, regulate, epigenetic, and, downstream, gene, regulatory, events, will, provide, insight, into, this, complex, question])]). relacion([sujeto(['Importantly,', 'lineage-defining', transcription, factors, that]), verbo([regulate]), complemento([epigenetic, events, have, the, potential, to, redefine, the, fate, of, the, cell, when, they, are, expressed])]). relacion([sujeto(['In', 'contrast,', factors, that]), verbo([regulate]), complemento([the, events, downstream, of, a, permissive, epigenetic, environment, will, only, have, the, capacity, to, modulate, the, underlying, gene, expression, profile, that, is, already, established, in, that, cell])]). relacion([sujeto(['Here,', we]), verbo([provide]), complemento([an, overview, of, these, topics, by, discussing, epigenetic, states, in, 'T', helper, cell, subtypes, as, well, as, the, mechanisms, by, which, 'lineage-defining', 'factors,', such, as, 'T-bet,', regulate, gene, expression, profiles, at, both, the, epigenetic, and, general, transcription, level])]). relacion([sujeto(['Defining', the, mechanisms, by, which, these, factors]), verbo([regulate]), complemento([gene, expression, profiles, will, aid, in, our, ability, to, predict, the, functional, capabilities, of, 'T', helper, cell, subsets])]). relacion([sujeto(['A', deeper, knowledge, of, the, molecular, basis, of, the, disease, may]), verbo([lead]), complemento([to, a, better, prediction, of, prognosis])]). relacion([sujeto(['Drug-induced', liver, injury, is, a, growing, concern, for, pharmaceutical, companies, and, patients, because, numerous, drugs]), verbo([have]), complemento([been, linked, to, hepatotoxicity, and, it, is, the, most, common, reason, for, a, drug, to, be, withdrawn])]). relacion([sujeto(['Flutamide', rarely]), verbo([causes]), complemento([liver, dysfunction, in, 'humans,', and, immune, allergic, reactions, have, been, suggested, in, some, cases])]). relacion([sujeto(['Plasma', alanine, aminotransferase, and, aspartate, aminotransferase, levels, were, significantly]), verbo([increased]), complemento([3, ',', 6, and, 9, h, after, flutamide, '(', 1500, mg, 'kg⁻¹', ',', p])]). relacion([sujeto(['The', biomarker, for, oxidative, stress, was, not, 'changed,', but, 'Th2-dominant', 'immune-related', 'factors,', such, as, interleukin, '(', 'IL)-4,', 'IL-5,', 'STAT6', and, 'GATA-binding', protein, '(', 'GATA)-3,', were]), verbo([induced]), complemento([in, 'flutamide-administered', mice])]). relacion([sujeto(['The', 'pre-administration', of, 'monoclonal-IL-4', antibody]), verbo([suppressed]), complemento([the, hepatotoxicity, of, flutamide])]). relacion([sujeto(['Coadministration', of, 'DK-PGD₂', and, flutamide, resulted, in, a, significant]), verbo([increase]), complemento([in, alanine, aminotransferase, and, a, remarkable, increase, of, macrophage, inflammatory, 'protein-2'])]). relacion([sujeto(['In', 'conclusion,', we, demonstrated, that, 'flutamide-induced', acute, liver, injury, is]), verbo([mediated]), complemento([by, 'Th2-dominant', immune, responses, in, mice])]). relacion([sujeto(['A', number, of, distinguished, populations, with, manifold, functions, and, various, pathways, of, differentiation]), verbo([have]), complemento([been, identified, within, 'T', lymphocytes])]). relacion([sujeto(['The', cells]), verbo([expressing]), complemento(['CD4', coreceptor, on, their, cell, surface, are, the, most, varied, group])]). relacion([sujeto(['Depending', on, changes, in, different, tissue, microenvironments]), verbo([induced]), complemento([by, such, cytokines, as, 'IL-4,', 'IFN-γ,', 'IL-10', or, 'TGF-β,', 'CD4+', 'T', lymphocytes, can, differentiate, into, alternative, subpopulations, performing, 'helper,', 'regulatory/suppressor', function, '(', 'Th1,', 'Th2,', 'Th9,', 'Th17,', 'Th22,', 'Tfh,', iTreg, and, 'Tr1)'])]). relacion([sujeto(['A', cytokine]), verbo([binding]), complemento([to, a, specific, receptor, activates, the, transcription, 'factors,', other, 'DNA-binding', 'proteins,', and, epigenetic, 'alterations,', enabling, the, transcription, of, proper, genetic, information])]). relacion([sujeto(['Even', 'more,', phenotypical, and, functional, borders, between, particular, subpopulations]), verbo([have]), complemento([turned, out, to, be, fluent])]). relacion([sujeto(['Systemic', autoimmune, diseases, like, 'lupus,', 'diabetes,', and, rheumatoid, arthritis]), verbo([have]), complemento([dysfunctional, effector, 'T', cells])]). relacion([sujeto(['To', determine, the, role, of, 'HDAC9', in, systemic, 'autoimmunity,', we, created, 'MRL/lpr', mice, with, 'HDAC9', deficiency, that]), verbo([have]), complemento([aberrant, effector, 'T', cell, function])]). relacion([sujeto(['HDAC9', deficiency]), verbo([led]), complemento([to, decreased, 'lympho-proliferation,', 'inflammation,', autoantibody, 'production,', and, increased, survival, in, 'MRL/lpr', mice])]). relacion([sujeto(['HDAC9-deficient', mice, manifested, 'Th2', 'polarization,']), verbo([decreased]), complemento(['T', effector, follicular, cells, positive, for, inducible, 'co-stimulator,', and, activated, 'T', cells, in, vivo, compared, with, 'HDAC9-intact', 'MRL/lpr', mice])]). relacion([sujeto(['HDAC9', deficiency, also, resulted, in]), verbo([increased]), complemento(['GATA3', and, roquin, and, decreased, 'BCL6', gene, expression])]). relacion([sujeto(['HDAC9', deficiency, was]), verbo([associated]), complemento([with, increased, 'site-specific', lysine, histone, acetylation, at, 'H3', '(', 'H3K9,', 'H3K14,', and, 'H3K18)', globally, that, was, localized, to, 'IL-4,', 'roquin,', and, peroxisome, 'proliferator-activated', 'receptor-γ', promoters, with, increased, gene, 'expression,', respectively])]). relacion([sujeto(['In', kidney, and, 'spleen,', 'HDAC9', deficiency]), verbo([decreased]), complemento([inflammation, and, cytokine, and, chemokine, production, due, to, peroxisome, 'proliferator-activated', receptor, γ, overexpression])]). relacion([sujeto(['These', findings]), verbo([suggest]), complemento([that, 'HDAC9', acts, as, an, epigenetic, switch, in, effector, 'T', 'cell-mediated', systemic, autoimmunity])]). relacion([sujeto(['GATA-3', and, 'STAT6']), verbo([bound]), complemento([several, regulatory, regions, in, the, gata3, locus, and, transactivated, the, expression, of, the, gata3, gene])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, 'Th2', differentiation, program, stimulates, 'feed-forward', regulation, of, gata3, gene, expression])]). relacion([sujeto(['Using', the, genome, sequences, and, gene, expression, data, from, multiple, 'species,', this, model, can, predict, regulatory, relationships, between, a, transcription, factor, '(', 'TF)', and, its]), verbo([target]), complemento([genes, in, all, 'species,', and, thus, identify, 'TN', 're-wiring', events])]). relacion([sujeto(['Applying', this, model, to, analyze, the, 'pre-implantation', development, of, three, mammalian, 'species,', we, identified, the]), verbo([conserved]), complemento([and, 're-wired', components, of, the, 'TNs', downstream, to, a, set, of, 'TFs', including, 'Oct4,', 'Gata3/4/6,', cMyc, and, nMyc])]). relacion([sujeto(['Evolutionary', events, on, the, 'DNA', sequence, that]), verbo([led]), complemento([to, turnover, of, 'TF', binding, sites, were, 'identified,', including, a, birth, of, an, 'Oct4', binding, site, by, a, 2, nt, deletion])]). relacion([sujeto(['In', contrast, to, recent]), verbo([reports]), complemento([of, large, interspecies, differences, of, 'TF', binding, sites, and, gene, expression, 'patterns,', the, interspecies, difference, in, 'TF-target', relationship, is, much, smaller])]). relacion([sujeto(['The', data, showed]), verbo([increasing]), complemento([conservation, levels, from, genomic, sequences, to, 'TF-DNA', 'interaction,', gene, 'expression,', 'TN,', and, finally, to, 'morphology,', suggesting, that, evolutionary, changes, are, larger, at, molecular, levels, and, smaller, at, functional, levels])]). relacion([sujeto(['The', data, also, showed, that, evolutionarily, older, 'TFs', are, more, likely, to]), verbo([have]), complemento([conserved, target, 'genes,', whereas, younger, 'TFs', tend, to, have, larger, 're-wiring', rates])]). relacion([sujeto(['The', role, of, 'Stat5', in]), verbo([maintaining]), complemento([adequate, lactation, was, studied, in, 'Stat5a(-/-)', mice, expressing, a, conditionally, suppressed, transgenic, 'STAT5', in, their, mammary, glands])]). relacion([sujeto(['Females', were, allowed, to]), verbo([express]), complemento(['STAT5', during, their, first, pregnancy])]). relacion([sujeto(['In', two, lines, of, genetically, modified, 'mice,', the, absence, of, 'STAT5', expression, during, the, first, 10, days, of, lactation, resulted, in, a]), verbo([decrease]), complemento([of, 29, '%', or, 41, '%', in, newborn, weight, gain])]). relacion([sujeto(['The', 'STAT5-dependent']), verbo([decrease]), complemento([in, growth, was, 'recoverable,', but, not, completely, 'reversible,', particularly, when, 'STAT5', expression, was, omitted, for, the, first, 4, days, of, lactation])]). relacion([sujeto(['By', 'Day', 10, ',', only, 18, '%', of, the, 'fat-pad', area, was]), verbo([involved]), complemento([in, milk, production])]). relacion([sujeto(['The', alveolar, regression]), verbo([caused]), complemento([by, 4, days, of, 'STAT5', deficiency, was, 'reversible,', but, neonate, growth, remained, delayed])]). relacion([sujeto(['An']), verbo([increase]), complemento([in, 'Gata-3', expression, may, reflect, an, attempt, to, maintain, alveolar, progenitors])]). relacion([sujeto(['A']), verbo([decrease]), complemento([of, 39, '%', and, 23, '%', in, 'WAP', and, 'α-lactalbumin', 'expression,', 'respectively,', with, no, associated, effects, on, 'β-casein,', also, resulted, from, lack, of, 'STAT5', expression, in, the, first, 10, days, of, lactation])]). relacion([sujeto(['This', deficiency]), verbo([enhances]), complemento([the, major, effect, of, alveolar, regression, on, delayed, weight, gain, in, newborns])]). relacion([sujeto(['Allergic', inflammation, affects]), verbo([target]), complemento(['cells,', such, as, epithelial, 'cells,', 'fibroblasts,', vascular, 'cells,', and, airway, smooth, muscle, 'cells,', which, become, an, important, source, of, inflammatory, mediators])]). relacion([sujeto(['Sensory', nerves, are, sensitized, and]), verbo([activated]), complemento([during, allergic, inflammation, and, produce, symptoms])]). relacion([sujeto(['Inflammatory', genes, are, also]), verbo([regulated]), complemento([by, epigenetic, 'mechanisms,', including, 'DNA', methylation, and, histone, modifications])]). relacion([sujeto(['Better', understanding, of, the, pathophysiology, of, allergic, inflammation]), verbo([has]), complemento([identified, new, therapeutic, targets, but, developing, effective, novel, therapies, has, been, challenging])]). relacion([sujeto(['Although', in, vitro, 'IL-4', directs, 'CD4', 'T', cells, to, produce, 'T', helper, 2, '(', 'Th2)-cytokines,', these, cytokines, can, be]), verbo([induced]), complemento([in, vivo, in, the, absence, of, 'IL-4-signalling'])]). relacion([sujeto(['The', pathway, for, in, vivo, 'IL-4-independent', 'Th2-differentiation']), verbo([has]), complemento([yet, to, be, characterized])]). relacion([sujeto(['Helios', '(', 'ikzf2),', a, member, of, the, 'Ikaros', transcription, regulator, 'family,', is]), verbo([expressed]), complemento([in, thymocytes, and, some, 'antigen-matured', 'T', cells, as, well, as, in, regulatory, 'T', cells])]). relacion([sujeto(['It']), verbo([has]), complemento([been, proposed, that, 'Helios', is, a, specific, marker, for, 'thymus-derived', regulatory, 'T', cells])]). relacion([sujeto(['Here,', we, show, that, mouse, 'ovalbumin-specific', 'CD4', '(', 'OTII)', cells]), verbo([responding]), complemento([to, 'alum-precipitated', ovalbumin, '(', 'alumOVA)', upregulate, 'Th2', features, -, 'GATA-3', and, 'IL-4', -, as, well, as, 'Helios', mRNA, and, protein])]). relacion([sujeto(['By', 'contrast,', 'OTII', cells]), verbo([responding]), complemento([to, the, 'Th1', antigen, -, live, attenuated, 'ovalbumin-expressing', 'Salmonella', -, upregulate, 'Th1', features, -, 'T-bet', and, 'IFN-γ', -, but, not, 'Helios'])]). relacion([sujeto(['In', 'addition,', 'CD4', 'T', cells]), verbo([induced]), complemento([to, produce, 'Th2', cytokines, in, vitro, do, not, express, 'Helios'])]). relacion([sujeto(['The', induction, of, 'IL-4,', 'IL-13', and, 'CXCR5', by, alumOVA]), verbo([requires]), complemento(['NF-κB1', and, this, is, also, needed, for, 'Helios', upregulation])]). relacion([sujeto(['Importantly,', 'Helios', is]), verbo([induced]), complemento([in, 'Th2', and, 'TFh', cells, without, parallel, upregulation, of, 'Foxp3'])]). relacion([sujeto(['These', findings]), verbo([suggested]), complemento([a, key, role, for, 'Helios', in, 'Th2', and, 'TFh', development, in, response, to, 'alum-protein', vaccines])]). relacion([sujeto(['We', tested, this, possibility, using, 'Helios-deficient', 'OTII', cells, and]), verbo([found]), complemento([this, deficiency, had, no, discernable, impact, on, 'Th2', and, 'TFh', differentiation, in, response, to, alumOVA])]). relacion([sujeto(['GATA3']), verbo([has]), complemento([been, identified, as, a, master, regulator, of, 'T', helper, 'cells,', as, well, as, being, important, for, early, thymic, progenitors, and, 'T-cell', commitment])]). relacion([sujeto(['Moreover,', through, 'long-term', primary, and, secondary, transplantation, 'experiments,', we, also, unequivocally, demonstrate, that, 'Gata3']), verbo([has]), complemento([a, redundant, role, in, 'post-transplantation', 'HSC', 'self-renewal'])]). relacion([sujeto(['We']), verbo([have]), complemento([reported, that, excessive, amounts, of, 'IL-13', are, produced, by, peripheral, blood, effector, 'CD8+', 'T', cells, from, patients, with, diffuse, cutaneous, 'SSc', '(', 'dcSSc)'])]). relacion([sujeto(['Freshly', isolated, naive, peripheral, blood, 'CD8+', 'T', cells]), verbo([expressed]), complemento([high, levels, of, 'GATA-3', and, failed, to, 'down-regulate', 'IL-13', production, when, cultured, under, type, 1, -, skewing, 'conditions,', but, maintained, adequate, levels, of, 'interferon-γ', production])]). relacion([sujeto(['These', results]), verbo([provide]), complemento([important, new, insights, into, 'SSc', pathogenesis, and, suggest, that, increased, 'GATA-3', expression, in, 'CD8+', 'T', cells, could, be, a, highly, relevant, biomarker, of, immune, dysfunction, in, patients, with, dcSSc])]). relacion([sujeto(['GATA-3', could, be, a, novel, therapeutic]), verbo([target]), complemento([for, this, currently, incurable, disease])]). relacion([sujeto(['In', this, 'review,', we, present, an, updated, view, on, the, molecular, mechanisms, through, which, 'GATA3']), verbo([regulates]), complemento(['T(h)1/T(h)2', differentiation])]). relacion([sujeto(['During', 'T(h)2', cell, 'differentiation,', 'GATA3', directly]), verbo([binds]), complemento([to, the, 'T(h)2', cytokine, gene, locus, at, several, regions, and, regulates, expression])]). relacion([sujeto(['On', the, other, 'hand,', 'GATA3']), verbo([inhibits]), complemento(['T(h)1', cell, differentiation, by, preventing, 'up-regulation', of, 'IL-12', receptor, β2, and, 'STAT4', '(', signal, transducer, and, activator, of, transcription, 4, ')', and, neutralization, of, 'Runx3', '(', 'runt-related', transcription, factor, 3, ')', function, through, 'protein-protein', interaction])]). relacion([sujeto(['GATA3', may, also, directly]), verbo([act]), complemento([on, the, 'Ifng', gene])]). relacion([sujeto(['In', 'summary,', 'GATA3', serves, as, a, transcriptional, activator, or, repressor, through, direct, action, on, transcriptional, machinery, 'and/or', affecting, chromatin, remodeling, at, many, critical, loci, encoding, 'cytokines,', cytokine, 'receptors,', signaling, molecules, as, well, as, transcription, factors, that, are]), verbo([involved]), complemento([in, the, regulation, of, 'T(h)1', and, 'T(h)2', differentiation])]). relacion([sujeto(['Allergic', asthma, is]), verbo([associated]), complemento([with, airway, 'eosinophilia,', which, is, regulated, by, different, 'T-effector', cells])]). relacion([sujeto(['T', cells]), verbo([express]), complemento([transcription, factors, 'T-bet,', 'GATA-3,', 'RORγt', and, 'Foxp3,', representing, 'Th1,', 'Th2,', 'Th17', and, 'Treg', cells, respectively])]). relacion([sujeto(['No', study]), verbo([has]), complemento([directly, determined, the, relative, presence, of, each, of, these, 'T', cell, subsets, concomitantly, in, a, model, of, allergic, airway, inflammation])]). relacion([sujeto(['Allergen', exposure]), verbo([increased]), complemento([the, numbers, of, 'T-bet(+),', 'GATA-3(+),', 'RORγt(+)', and, 'Foxp3(+)', cells, in, 'CD4(+)CD25(+)', and, 'CD4(+)CD25(-)', 'T', 'cells,', with, the, greatest, expansion, of, 'GATA-3(+)', cells])]). relacion([sujeto(['Allergen', exposure]), verbo([led]), complemento([to, the, accumulation, of, 'T-bet(+),', 'GATA-3(+)', and, 'Foxp3(+)', cells, in, peribronchial, and, alveolar, 'tissue,', 'GATA-3(+)', and, 'Foxp3(+)', cells, in, perivascular, 'tissue,', and, 'RORγt(+)', cells, in, alveolar, tissue])]). relacion([sujeto(['The', posttranscriptional, mechanisms, whereby, 'RNA-binding', proteins, '(', 'RBPs)']), verbo([regulate]), complemento(['T', cell, differentiation, remain, unclear])]). relacion([sujeto(['RBPs', can, coordinately]), verbo([regulate]), complemento([the, expression, of, functionally, related, genes, via, binding, to, shared, regulatory, 'sequences,', such, as, the, 'adenylate-uridylate-rich', elements, '(', 'AREs)', present, in, the, 3, '\'', untranslated, region, '(', 'UTR)', of, mRNA])]). relacion([sujeto(['The', 'RBP', 'HuR', posttranscriptionally]), verbo([regulates]), complemento(['IL-4,', 'IL-13,', and, other, 'Th2', 'cell-restricted', transcripts])]). relacion([sujeto(['We']), verbo([report]), complemento([that, in, parallel, with, 'stimulus-induced', increase, in, 'GATA-3', mRNA, and, protein, 'levels,', 'GATA-3', mRNA, 'half-life', is, increased, after, restimulation, in, the, human, 'T', cell, line, 'Jurkat,', in, human, memory, and, 'Th2', 'cells,', and, in, murine, 'Th2-skewed', cells])]). relacion([sujeto(['We', demonstrate, by, immunoprecipitation, of, ribonucleoprotein, complexes, that, 'HuR']), verbo([associates]), complemento([with, the, 'GATA-3', endogenous, transcript, in, human, 'T', cells, and, 'found,', using, biotin, pulldown, 'assay,', that, 'HuR', specifically, interacts, with, its, 3, '\'', 'UTR'])]). relacion([sujeto(['Using', both, 'loss-of-function', and, 'gain-of-function', approaches, in, vitro, and, in, animal, 'models,', we, show, that, 'HuR', is, a, critical, mediator, of, 'stimulus-induced']), verbo([increase]), complemento([in, 'GATA-3', mRNA, and, protein, expression, and, that, it, positively, influences, 'GATA-3', mRNA, 'turnover,', in, parallel, with, selective, promotion, of, 'Th2', cytokine, overexpression])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, 'HuR-driven', posttranscriptional, control, plays, a, significant, role, in, 'T', cell, development, and, effector, function, in, both, murine, and, human, systems])]). relacion([sujeto(['A', better, understanding, of, 'HuR-mediated', control, of, 'Th2', polarization, may]), verbo([have]), complemento([utility, in, altering, allergic, airway, inflammation, in, human, asthmatic, patients])]). relacion([sujeto(['Naïve', 'CD4(+)', 'T', helper, '(', 'Th)', cells, differentiate, into, distinct, subsets, of, effector, cells, '(', 'Th1,', 'Th2,', 'Th17,', and]), verbo([induced]), complemento([regulatory, 'T', cells, '(', 'iTreg))', expressing, different, sets, of, cytokines, upon, encounter, with, presented, foreign, antigens])]). relacion([sujeto(['It']), verbo([has]), complemento([been, well, established, that, 'Th1/Th2', balance, is, critical, for, the, nature, of, the, following, immune, responses])]). relacion([sujeto(['Previous']), verbo([reports]), complemento([have, demonstrated, important, roles, of, 'c-Jun', 'N-terminal', kinase, '(', 'JNK)', in, 'Th1/Th2', 'balance,', whereas, the, regulatory, mechanisms, of, 'JNK', activity, in, 'Th', cells, have, not, been, elucidated])]). relacion([sujeto(['Here,', we, show, that, dual, specificity, phosphatase, 16, '(', 'DUSP16,', also, referred, to, as, 'MKP-M', or, 'MKP-7),', which, preferentially, inactivates, 'JNK,', is, selectively]), verbo([expressed]), complemento([in, 'Th2', cells])]). relacion([sujeto(['Chromatin', immunoprecipitation, revealed, the]), verbo([increased]), complemento([acetylation, of, histone, 'H3/H4', at, the, dusp16, gene, promoter, in, 'CD4(+)', 'T', cells, under, the, 'Th2', condition])]). relacion([sujeto(['Adenoviral', transduction, of, naïve, 'CD4(+)', 'T', cells, with, 'DUSP16', resulted, in]), verbo([increased]), complemento([mRNA, expression, of, 'IL-4', and, 'GATA-3', in, 'Th2', and, decreased, expression, of, 'IFNγ', and, 'T-bet', in, 'Th1', differentiation])]). relacion([sujeto(['Furthermore,', upon, 'immunization,', 'T', 'cell-specific', dusp16, transgenic, mice, produced, 'antigen-specific', 'IgG2a', at, lower, 'amounts,', whereas, 'DN', dusp16, transgenic, mice, produced, higher, amounts, of, 'antigen-specific', 'IgG2a', accompanied, by]), verbo([decreased]), complemento([amounts, of, 'antigen-specific', 'IgG1', and, 'IgE', than, those, of, control, mice])]). relacion([sujeto(['Together,', these, data]), verbo([suggest]), complemento([the, functional, role, of, 'DUSP16', in, 'Th1/Th2', balance])]). relacion([sujeto(['Psoriasis', is, characterized, by, hyperproliferation, of, keratinocytes, and, by, infiltration, of]), verbo([activated]), complemento(['Th1', and, 'Th17', cells, in, the, '(', 'epi)dermis'])]). relacion([sujeto(['By', expression, 'microarray,', we, previously]), verbo([found]), complemento([the, 'GATA3', transcription, factor, significantly, downregulated, in, lesional, psoriatic, skin])]). relacion([sujeto(['Psoriatic', lesional, skin, showed]), verbo([decreased]), complemento(['GATA3', mRNA, and, protein, expression, compared, to, 'non-lesional', skin])]). relacion([sujeto(['GATA3', expression, was, also, markedly]), verbo([decreased]), complemento([in, inflamed, skin, of, mice, with, a, psoriasiform, dermatitis, induced, with, imiquimod])]). relacion([sujeto(['The', prototypic, 'Th2', cytokine, 'IL-4', was, the, only, cytokine, capable, of]), verbo([inducing]), complemento(['GATA3', in, skin, explants, from, healthy, donors])]). relacion([sujeto(['Numerous', transcription, factors, that]), verbo([regulate]), complemento([trophoblast, developmental, processes, have, been, 'identified;', 'however,', the, regulation, of, 'trophoblast-specific', gene, expression, has, not, been, definitively, characterized])]). relacion([sujeto(['In', this, 'study,', expression, patterns, of, trophoblast, 'ASCL2,', 'CDX2,', 'CSH1,', 'ELF5,', 'HAND1,', 'IFNT,', and, 'TKDP1', mRNAs, were, initially, 'examined,', from, which, 'ASCL2,', 'CDX2,', 'IFNT,', and, 'TKDP1', mRNAs, were]), verbo([found]), complemento([to, be, similar, to, those, of, 'GATA2', and, 'GATA3', in, days, 17, ',', 20, ',', and, 22, '(', day, 0, =, day, of, 'estrus)', bovine, conceptuses])]). relacion([sujeto(['A', chromatin, immunoprecipitation, '(', 'ChIP)', assay, revealed, that, endogenous, 'GATA2', and, 'GATA3', occupied, 'GATA']), verbo([binding]), complemento([sites, on, the, upstream, regions, of, 'CSH1,', 'IFNT,', and, 'TKDP1', genes, and, on, the, intron, 1, region, of, 'CDX2', gene, in, bovine, trophoblast, 'CT-1', cells])]). relacion([sujeto(['In', transient, transfection, analyses, of, the, upstream, region, of, bovine, 'CSH1,', and, 'IFNT', or, the, intron, 1, region, of, 'CDX2', 'gene,', 'over-expression', of, 'GATA2']), verbo([induced]), complemento([transactivation, of, these, 'trophoblast-specific', genes, in, bovine, 'non-trophoblast', ear, fibroblast, 'EF', 'cells,', but, 'over-expression', of, 'GATA3', did, not, substantially, affect, their, transactivation])]). relacion([sujeto(['Our', results, indicate, that, in, addition, to, trophectoderm, lineage, 'specification,', 'GATA2', 'and/or', 'GATA3', are]), verbo([involved]), complemento([in, the, regulation, of, 'trophoblast-specific', gene, transcription, in, bovine, trophoblast, 'CT-1', cells])]). relacion([sujeto(['Vitamin', 'D']), verbo([has]), complemento([several, reported, immunomodulatory, properties, including, the, reduced, generation, of, 'pro-inflammatory', 'CD4+', 'T', helper, 1, '(', 'Th1)', cells, and, the, increase, in, levels, of, the, 'anti-inflammatory', 'Th2', subset])]). relacion([sujeto(['Less', clear]), verbo([has]), complemento([been, the, impact, of, vitamin, 'D', on, the, 'pro-inflammatory', 'Th17', 'subset,', and, whether, and, how, vitamin, 'D', may, preferentially, drive, the, polarization, of, one, of, the, 'T', helper, subsets])]). relacion([sujeto(['We']), verbo([report]), complemento([that, the, biologically, active, form, of, vitamin, 'D,', 1, ',', 25, -, dihydroxyvitamin, 'D3', '{', 1, ',', 25, '(', 'OH)2D3},', consistently, generates, human, and, murine, 'Th2', cells, in, 'culture,', frequently, leaving, unchanged, the, levels, of, 'Th1/Th17', cytokines])]). relacion([sujeto(['As', a, 'result,', the, ratio, of, 'Th2', to, 'Th1', and, 'Th17', is]), verbo([increased]), complemento([by, 1, ',', 25, '(', 'OH)2D3'])]). relacion([sujeto(['The', upregulation, of, 'Th2', to, 'Th1', or, 'Th17', subsets, by, 1, ',', 25, '(', 'OH)2D3', is, enabled, by, an]), verbo([increase]), complemento([of, the, 'GATA-3', transcription, 'factor,', which, itself, is, promoted, upstream, by, an, elevation, of, the, 'STAT6', transcription, factor])]). relacion([sujeto(['These', results, of, vitamin, 'D']), verbo([promoting]), complemento([a, 'Th2', shift, through, upstream, 'GATA-3', and, 'STAT6', transcription, factors, shed, mechanistic, understanding, on, the, utility, of, vitamin, 'D', in, 'MS'])]). relacion([sujeto(['Although', exposure, to, toluene, alone, for, 6, weeks, did, not]), verbo([increase]), complemento([the, number, of, inflammatory, cells, in, bronchoalveolar, lavage, '(', 'BAL)', 'fluid,', coexposure, to, 50, ppm, toluene, and, 'OVA', increased, the, number, of, 'BAL', cells])]). relacion([sujeto(['Histological', changes, and]), verbo([increased]), complemento([amounts, of, fibronectin, were, observed, in, the, lungs, of, 'OVA-immunized,', 50, -, 'ppm-toluene-exposed', mice])]). relacion([sujeto(['Exposure', to, 500, ppm, significantly]), verbo([increased]), complemento([the, expressions, of, transcription, factors, 'STAT3,', 'STAT4', and, 'STAT5a', mRNAs, in, spleen])]). relacion([sujeto(['In', spleens, from, the, allergic, mouse, 'model,', the, expressions, of, 'STAT3,', 'STAT4,', 'STAT5a,', 'STAT6,', 'GATA3', and, 'Foxp3', mRNAs, were, significantly]), verbo([enhanced]), complemento([following, exposure, to, 50, ppm, toluene, for, 6, 'weeks,', but, the, expression, of, 'T-bet', mRNA, was, not, increased])]). relacion([sujeto(['Regarding', the, 'Th1/Th2', 'balance,', the, expressions, of, 'IL-4', and, 'IL-12', mRNAs, were]), verbo([enhanced]), complemento([in, the, spleens, of, 'toluene-exposed', mice])]). relacion([sujeto(['Total', 'IgG1', antibody, production, in, the, plasma, was, significantly]), verbo([increased]), complemento([in, the, 50, -, 'ppm-toluene-exposed', allergic, mouse, model])]). relacion([sujeto(['Extensive', 'in vitro', manipulation, reprograms, 'T(H)2 and', 'T(H)17', cell, lines, into, 'T(H)1', 'cells,']), verbo([leading]), complemento([to, the, concept, of, 'CD4(+)', 'T(H)', cell, subset, plasticity])]). relacion([sujeto(['We', show, that, repetitive, administration, of, inflammatory, 'ovalbumin-DCs,', locally, or, 'systemically,']), verbo([promoted]), complemento([the, development, of, 'antigen-specific', 'T(H)17/T(H)2', cells, in, lungs, and, mediastinal, lymph, nodes])]). relacion([sujeto(['We', demonstrate, the, existence, of, 'T(H)17/T(H)2', cells, that]), verbo([express]), complemento(['GATA-3', in, inflamed, tissues, and, their, 'T(H)17', origin])]). relacion([sujeto(['A', 'well-known', association, between, vitamin, 'D(3)', and, infection, with, 'Mycobacterium', tuberculosis]), verbo([has]), complemento([previously, been, 'reported,', but, little, is, known, regarding, the, underlying, mechanisms])]). relacion([sujeto(['We']), verbo([have]), complemento([investigated, how, 1, ',', 25, -, dihydroxyvitamin, 'D(3)', '[', 1, ',', 25, '(', 'OH)(2)D(3)]', affects, the, proinflammatory, cytokine, production, induced, by, 'M'])]). relacion([sujeto(['tuberculosis,', 1, ',', 25, '(', 'OH)(2)D(3)']), verbo([induced]), complemento([a, 'dose-dependent', 'down-regulation', of, 'IL-6,', 'TNFα', and, 'IFNγ,', while, increasing, the, production, of, 'IL-10', in, culture, supernatant, as, well, as, cathelicidin, mRNA, expression])]). relacion([sujeto(['The', mechanism, whereby, 1, ',', 25, '(', 'OH)(2)D(3)']), verbo([inhibited]), complemento([the, proinflammatory, cytokine, response, was, through, reduced, expression, of, the, pattern, recognition, receptors, '(', 'PRR)', -, 'TLR2,', 'TLR4,', 'Dectin-1', and, mannose, 'receptor,', whose, mRNA, and, protein, expression, were, both, reduced])]). relacion([sujeto([tuberculosis, 'stimulation,', 1, ',', 25, '(', 'OH)(2)D(3)']), verbo([modulates]), complemento([the, balance, in, cytokine, production, towards, an, 'anti-inflammatory', profile, by, repression, of, 'TLR2,', 'TLR4,', 'Dectin-1', and, mannose, receptor, 'expression,', while, increasing, cathelicidin, production])]). relacion([sujeto(['These', two, effects, may]), verbo([have]), complemento([beneficial, 'consequences,', by, reducing, the, collateral, tissue, damage, induced, by, proinflammatory, 'cytokines,', while, the, antibacterial, effects, of, cathelicidin, are, enhanced])]). relacion([sujeto(['Hepatoid', adenocarcinoma, is, a, rare, 'neoplasm,', which]), verbo([has]), complemento([a, striking, morphologic, similarity, to, hepatocarcinoma])]). relacion([sujeto(['It']), verbo([has]), complemento([been, described, in, different, 'organs,', the, most, common, are, 'stomach,', 'lung,', and, pancreas])]). relacion([sujeto(['This', tumor]), verbo([has]), complemento([a, pattern, similar, to, the, hepatocarcinoma])]). relacion([sujeto(['Here,', we]), verbo([report]), complemento([the, case, of, an, old, female, patient, affected, by, hepatoid, adenocarcinoma, of, the, ureter, with, 'ovarian,', small, 'intestine,', and, hepatic, involvement])]). relacion([sujeto(['Inter-species', somatic, cell]), verbo([nuclear]), complemento([transfer, '(', 'iSCNT)', embryos, usually, fail, to, develop, to, the, blastocyst, stage, and, beyond, due, to, incomplete, reprogramming, of, donor, cell])]). relacion([sujeto(['We', evaluated, whether, using, a, karyoplast, that, would]), verbo([require]), complemento([less, extensive, reprogramming, such, as, an, embryonic, blastomere, or, the, meiotic, spindle, from, metaphase, 'II', oocytes, would, provide, additional, insight, into, the, development, of, iSCNT, embryos])]). relacion([sujeto(['Our', results, showed, that, karyoplasts, of, embryonic, or, oocyte, origin, are, no, different, from, somatic, 'cells;', all, iSCNT, 'embryos,', irrespective, of, karyoplast, 'origin,', were]), verbo([arrested]), complemento([during, early, development])]). relacion([sujeto(['These', results, demonstrate, that, the, presence, of, even, a, small, amount, of, porcine, cytoplasm, is, detrimental, to, murine, embryo, development, and]), verbo([suggest]), complemento([that, a, range, of, factors, are, likely, to, contribute, to, the, failure, of, 'inter-species', nuclear, transfer, embryos])]). relacion([sujeto(['Haploinsufficiency', of, 'Gata3']), verbo([causes]), complemento(['hypoparathyroidism,', deafness, and, renal, dysplasia, '(', 'HDR)', syndrome, in, mice, and, humans])]). relacion([sujeto(['Gata3', null, mutation]), verbo([leads]), complemento([to, early, lethality, around, embryonic, day, '(', 'E)11'])]). relacion([sujeto(['However,', using, rescued, mice, we]), verbo([found]), complemento([that, some, morphogenesis, and, neurosensory, development, is, possible, in, the, ear, without, 'Gata3'])]). relacion([sujeto(['Extending', previous, 'studies,', we]), verbo([find]), complemento([that, at, 'E16'])]). relacion([sujeto(['In', situ, hybridization, studies]), verbo([reveal]), complemento([altered, expression, of, several, transcription, factors, relevant, to, ear, development, and, we, hypothesize, that, this, may, relate, to, the, observed, dysmorphia, and, restricted, neurosensory, development])]). relacion([sujeto(['Gata3', null, mutant, phenocopies, the, otic, maldevelopment, '(', cochlear, duct, formation, in, the, absence, of, neurosensory, 'development)', seen, in, 'Foxg1cre']), verbo([mediated]), complemento([conditional, deletion, of, microRNA, processing, 'enzyme,', 'Dicer1'])]). relacion([sujeto(['Finally,', while, 'GATA3', is]), verbo([expressed]), complemento([in, the, developing, 'vestibulo-cochlear', efferent, '(', 'VCE)', 'neurons,', and, its, absence, in, the, null, mutants, disrupts, 'VCE', projections, to, the, 'ear,', loss, of, 'GATA3', does, not, affect, 'VCE', progenitor, cell, migration])]). relacion([sujeto([1, ')', and, was]), verbo([associated]), complemento([with, a, clinical, expression, of, glomerulitis])]). relacion([sujeto(['Our', results]), verbo([suggest]), complemento([that, the, balance, of, 'Th1/Th2', is, likely, to, differentiate, clinical, expression, of, transplant, glomerulopathy])]). relacion([sujeto(['Differentiation', of, sympathetic, neurons, is, controlled, by, a, group, of, transcription, 'factors,', including, 'Phox2b,', 'Ascl1,', 'Hand2', and, 'Gata3,']), verbo([induced]), complemento([by, bone, morphogenetic, proteins, '(', 'BMPs)', in, progenitors, located, in, ganglion, primordia, at, the, dorsal, aorta])]). relacion([sujeto(['Here,', we, address, the, function, of, the, transcription, factors, 'AP-2β', and, 'AP-2α,']), verbo([expressed]), complemento([in, migrating, neural, crest, cells, '(', 'NCC)', and, maintained, in, sympathetic, progenitors, and, differentiated, neurons])]). relacion([sujeto(['In', the, 'AP-2β', knockout, only, sympathetic, ganglia, '(', 'SG)', are, 'targeted,']), verbo([leading]), complemento([to, a, reduction, in, ganglion, size, by, about, 40, '%', ',', which, is, also, caused, by, apoptotic, death, of, neural, crest, progenitors])]). relacion([sujeto(['The', conditional, double, knockout, of, 'AP-2α', and, 'AP-2β', in, sympathetic, progenitors, and, differentiated, noradrenergic, neurons, results, in, a, further]), verbo([decrease]), complemento([in, neuron, 'number,', leading, eventually, to, small, sympathetic, ganglion, rudiments, postnatally])]). relacion([sujeto(['The', elimination, of, 'AP-2β', also]), verbo([leads]), complemento([to, the, complete, absence, of, noradrenergic, neurons, of, the, 'Locus', coeruleus, '(', 'LC)'])]). relacion([sujeto(['Whereas', 'AP-2α/β', transcription, factors, are, in, vivo, not]), verbo([required]), complemento([for, the, onset, or, maintenance, of, noradrenergic, 'differentiation,', their, essential, survival, functions, are, demonstrated, for, sympathetic, progenitors, and, noradrenergic, neurons])]). relacion([sujeto(['GATA']), verbo([binding]), complemento([protein, 3, '(', 'GATA3)', is, a, key, molecule, regulating, the, balance, in, the, ratio, of, type, 1, helper, 'T', '(', 'Th1)', cells, to, type, 2, helper, 'T', '(', 'Th2)', 'cells,', which, is, thought, to, be, indicative, of, the, pathogenesis, of, allergic, diseases, such, as, asthma, and, atopic, dermatitis])]). relacion([sujeto(['The', hGATA3, gene, was, successfully]), verbo([expressed]), complemento([at, the, protein, level, in, the, lymph, node, and, thymus, of, 'CMV/hGATA3', transfected, cells, and, 'Tg', mice])]). relacion([sujeto(['CMV/hGATA3', 'Tg', mice, showed, a, significant]), verbo([increase]), complemento([in, the, allergic, skin, inflammation, response, such, as, ear, 'thickness,', draining, auricular, lymph, node, '(', 'aLN)', 'weight,', epidermal, 'thickness,', inflammatory, cell, number, and, 'Th2', immunoglobulin, '(', 'Ig)', concentration, compared, to, 'wild-type', '(', 'WT)', mice, after, phthalic, anhydride, '(', 'PA)', treatment])]). relacion([sujeto(['Furthermore,', the, secretion, of, 'Th2', type, cytokines, was]), verbo([increased]), complemento([by, 'PA', treatment, in, 'CMV/hGATA3', 'Tg', 'mice,', while, the, secretion, of, 'Th1', type, cytokine, was, suppressed, under, the, same, conditions])]). relacion([sujeto(['However,', the]), verbo([increased]), complemento([levels, of, 'Th2', type, cytokines, in, 'CMV/hGATA3', 'Tg', mice, were, almost, recovered, by, the, 'down-regulation', of, 'GATA3', expression, with, 'D-pinitol', treatment])]). relacion([sujeto(['Therefore,', these, findings]), verbo([suggest]), complemento([that, 'GATA3', could, be, considered, as, a, potential, target, regulating, the, mechanism, responsible, for, the, differences, in, allergic, skin, inflammation])]). relacion([sujeto(['The', 'Ets-related', gene, '(', 'ERG)', is, an, 'Ets-transcription', factor]), verbo([required]), complemento([for, normal, blood, stem, cell, development])]). relacion([sujeto(['ERG', expression, is, 'down-regulated', during, early, 'T-lymphopoiesis', but]), verbo([maintained]), complemento([in, 'T-acute', lymphoblastic, leukemia, '(', 'T-ALL),', where, it, is, recognized, as, an, independent, risk, factor, for, adverse, outcome])]). relacion([sujeto(['However,', it, is, unclear, whether, 'ERG', is, directly]), verbo([involved]), complemento([in, the, pathogenesis, of, 'T-ALL', and, how, its, expression, is, regulated])]). relacion([sujeto(['Here', we, demonstrate, that, transgenic, expression, of, 'ERG']), verbo([causes]), complemento(['T-ALL', in, mice, and, that, its, knockdown, reduces, the, proliferation, of, human, 'MOLT4', 'T-ALL', cells])]). relacion([sujeto(['We', further, demonstrate, that, 'ERG', expression, in, primary, human, 'T-ALL', cells, is]), verbo([mediated]), complemento([by, the, binding, of, other, 'T-cell', oncogenes, 'SCL/TAL1,', 'LMO2,', and, 'LYL1', in, concert, with, 'ERG,', 'FLI1,', and, 'GATA3', to, the, 'ERG', +, 85, enhancer])]). relacion([sujeto(['This', enhancer, is, not, active, in, normal, 'T', cells, but, in, transgenic, mice]), verbo([targets]), complemento([expression, to, fetal, liver, 'c-kit(+)', 'cells,', adult, bone, marrow, 'stem/progenitors', and, early, 'CD4(-)CD8(-)', 'double-negative', thymic, progenitors])]). relacion([sujeto(['Taken', 'together,', these, data, illustrate, that, 'ERG']), verbo([promotes]), complemento(['T-ALL', and, that, failure, to, extinguish, activity, of, stem, cell, enhancers, associated, with, regulatory, transcription, factors, such, as, 'ERG', can, contribute, to, the, development, of, leukemia])]). relacion([sujeto(['Differentiation', of, naive, 'CD4', 'T', cells, into, 'Th2', cells, is, accompanied, by, chromatin, remodeling, and]), verbo([increased]), complemento([expression, of, a, set, of, 'Th2-specific', 'genes,', including, those, encoding, 'Th2', cytokines])]). relacion([sujeto(['IL-4-mediated', 'STAT6', activation]), verbo([induces]), complemento([high, levels, of, transcription, of, 'GATA3,', a, master, regulator, of, 'Th2', cell, 'differentiation,', and, enforced, expression, of, 'GATA3', induces, 'Th2', cytokine, expression])]). relacion([sujeto(['However,', it, remains, unclear, whether, the, expression, of, other, 'Th2-specific', genes, is]), verbo([induced]), complemento([directly, by, 'GATA3'])]). relacion([sujeto(['A', 'genome-wide', unbiased, chromatin, immunoprecipitation, assay, coupled, with, massive, parallel, sequencing, analysis, revealed, that, 'GATA3']), verbo([bound]), complemento([to, 1279, genes, selectively, in, 'Th2', 'cells,', and, 101, genes, in, both, 'Th1', and, 'Th2', cells])]). relacion([sujeto(['We', assessed, dependency, on, 'GATA3', for, the, transcription, of, these, 26, 'Th2-specific', 'genes,', and, 10, genes, showed]), verbo([increased]), complemento([transcription, in, a, 'GATA3-dependent', 'manner,', whereas, 16, genes, showed, no, significant, responses])]). relacion([sujeto(['The', transcription, of, the, 16, 'GATA3-nonresponding', genes, was, clearly]), verbo([increased]), complemento([by, the, introduction, of, an, active, form, of, 'STAT6,', 'STAT6VT'])]). relacion([sujeto(['Therefore,', although, 'GATA3']), verbo([has]), complemento([been, recognized, as, a, master, regulator, of, 'Th2', cell, 'differentiation,', many, 'Th2-specific', genes, are, not, regulated, by, 'GATA3', 'itself,', but, in, collaboration, with, 'STAT6'])]). relacion([sujeto(['We', previously]), verbo([reported]), complemento([that, 'Lgr4', has, a, critical, role, in, the, morphogenesis, of, 'kidney,', but, the, detailed, functions, of, 'Lgr4', in, kidney, development, have, not, been, elucidated])]). relacion([sujeto([5, in, the, 'Lgr4(-/-)', was]), verbo([arrested]), complemento(['earlier,', and, both, 'DBA-lectin', staining, and, immunohistochemical, analysis, using, 'Aqp3', antibodies, showed, that, the, ureteric, bud, '(', 'UB)', of, 'Lgr4(-/-)', kidneys, underwent, premature, differentiation])]). relacion([sujeto(['Furthermore,', quantitative, 'RT-PCR', and, histological, analysis]), verbo([suggested]), complemento([that, the, impaired, 'UB', differentiation, was, caused, by, 'down-regulation', of, the, 'Wnt', pathway, and, 'Gata3', in, the, 'Lgr4(-/-)', kidneys])]). relacion([sujeto(['We', demonstrate, here, that, 'Lgr4']), verbo([has]), complemento([a, novel, function, for, maintaining, the, 'UB', in, an, undifferentiated, state])]). relacion([sujeto(['Defects', in, this, maturation, process, can, result, in, malpositioned, ureters, and, 'hydronephrosis,', a, common]), verbo([cause]), complemento([of, renal, disease, in, children])]). relacion([sujeto(['Here,', we]), verbo([report]), complemento([that, insertion, of, the, 'ND', into, the, cloaca, is, an, unrecognized, but, crucial, step, that, is, required, for, proper, positioning, of, the, ureter, and, that, depends, on, 'Ret', signaling])]). relacion([sujeto(['Analysis', of, 'Ret', mutant, mice, at, birth]), verbo([reveals]), complemento([hydronephrosis, and, defective, ureter, 'maturation,', abnormalities, that, our, results, suggest, are, 'caused,', at, least, in, 'part,', by, delayed, insertion, of, the, 'ND'])]). relacion([sujeto(['We']), verbo([find]), complemento([a, similar, set, of, malformations, in, mutants, lacking, either, 'Gata3', or, 'Raldh2'])]). relacion([sujeto(['We', show, that, these, factors]), verbo([act]), complemento([in, parallel, to, regulate, 'ND', insertion, via, 'Ret'])]). relacion([sujeto(['Morphological', analysis, of, 'ND', extension, in, 'wild-type', embryos]), verbo([reveals]), complemento([elaborate, cellular, protrusions, at, 'ND', tips, that, are, not, detected, in, 'Ret,', 'Gata3', or, 'Raldh2', mutant, 'embryos,', suggesting, that, these, protrusions, may, normally, be, important, for, fusion, with, the, cloaca])]). relacion([sujeto(['Together,', our, studies]), verbo([reveal]), complemento([a, novel, 'Ret-dependent', 'event,', 'ND', 'insertion,', 'that,', when, 'abnormal,', can, cause, obstruction, and, hydronephrosis, at, 'birth;', whether, 'ND', defects, underlie, similar, types, of, urinary, tract, abnormalities, in, humans, is, an, interesting, possibility])]). relacion([sujeto(['The', molecular, mechanism]), verbo([involved]), complemento([in, 'COX-2-', and, 'PGE2-mediated', production, of, immunosuppressive, cytokine, 'IL-10', is, not, 'well-understood'])]). relacion([sujeto(['In', comparison, to, healthy, 'individual,', a, marked]), verbo([decrease]), complemento([in, lymphocyte, proliferation, to, 'anti-CD3', 'MAb', was, observed, in, 'NSCLC', patients, by, thymidine, incorporation, assay])]). relacion([sujeto(['Using', flow, 'cytometry,']), verbo([decrease]), complemento([in, intracellular, calcium, release, with, increase, in, reactive, oxygen, species, was, observed, in, lymphocytes, of, 'NSCLC', patients])]). relacion([sujeto(['These', patients, showed]), verbo([increased]), complemento(['IL-10', and, 'PGE2', with, reduced, 'IFN-γ', production, by, 'ELISA'])]). relacion([sujeto(['IL-10/IFN-γ', levels, were]), verbo([found]), complemento([to, be, differentially, regulated, via, p38, and, 'ERK', 'mitogen-activated', protein, kinase, '(', 'MAPK)', pathways, in, cooperation, with, 'COX-2'])]). relacion([sujeto(['Inhibition', of, these, pathways, using, selective, inhibitors]), verbo([lead]), complemento([to, increased, lymphocyte, proliferative, response, to, 'anti-CD3', 'MAb', and, 'IFN-γ', production, with, decrease, in, 'IL-10', production])]). relacion([sujeto(['Regionalization', of, the, central, nervous, system, is, controlled, by, local, networks, of, transcription, factors, that, establish, and]), verbo([maintain]), complemento([the, identities, of, neuroepithelial, progenitor, areas, and, their, neuronal, derivatives])]). relacion([sujeto(['The']), verbo([conserved]), complemento([cerebral, 'Bauplan', of, vertebrates, must, result, essentially, from, conserved, patterns, of, developmentally, expressed, transcription, factors])]). relacion([sujeto(['We']), verbo([have]), complemento([previously, produced, detailed, molecular, maps, for, the, alar, plate, of, prosomere, 1, '(', the, pretectal, 'region)', in, chicken, '(', 'Ferran', et, al])]). relacion([sujeto(['However,', we]), verbo([found]), complemento([that, at, corresponding, developmental, stages, the, pretectal, region, of, 'G'])]). relacion([sujeto(['Altogether,', our, results, on, a]), verbo([conserved]), complemento([genoarchitectonic, pattern, highlight, the, importance, of, early, developmental, gene, networks, that, causally, underlie, the, production, of, homologous, derivatives, in, these, two, evolutionarily, closely, related, species])]). relacion([sujeto(['Recombinant', hemagglutinin, 'B', '(', 'rHagB),', a, virulence, factor, of, the, periodontal, pathogen, 'Porphyromonas', 'gingivalis,']), verbo([has]), complemento([been, shown, to, induce, protective, immunity, against, bacterial, infection])]). relacion([sujeto(['Furthermore,', we]), verbo([have]), complemento([demonstrated, that, rHagB, is, a, 'TLR4', agonist, for, dendritic, cells])]). relacion([sujeto(['In', 'TLR4(-/-)', and, 'MyD88(-/-)', but, not, 'Toll/IL-1R', 'domain-containing', adapter]), verbo([inducing]), complemento(['IFN-β-deficient', '(', 'TRIF(Lps2))', 'mice,', there, was, an, increase, in, the, 'Th2', 'CD4(+)', 'T', cell, 'subset,', a, decrease, in, the, 'Th1', 'subset,', and, higher, serum, 'IgG(1)/IgG(2)', levels, of, 'HagB-specific', 'Abs', compared, with, those, in, 'wild-type', mice])]). relacion([sujeto(['These']), verbo([finding]), complemento([were, accompanied, by, increased, 'GATA-3', and, 'Foxp3', expression, and, a, decrease, in, the, activation, of, 'CD4(+)', 'T', cells, isolated, from, 'TLR4(-/-)', and, 'MyD88(-/-)', mice])]). relacion([sujeto(['Interestingly,', 'TLR4(-/-)', 'CD4(+)', 'T', cells, showed, an]), verbo([increase]), complemento([in, 'IL-2/STAT5', signaling])]). relacion([sujeto(['Whereas', 'TRIF', deficiency, had, minimal, effects, on, the, 'CD4(+)', 'T', cell, 'response,', it, resulted, in]), verbo([increased]), complemento(['IFN-γ', and, 'IL-17', production, by, memory, 'CD4(+)', 'T', cells])]). relacion([sujeto(['Familial', aggregation, of, this, disease]), verbo([suggests]), complemento([that, at, least, part, of, the, susceptibility, for, this, disease, is, 'genetic,', although, environmental, and, hormonal, influences, are, also, likely, to, play, a, role])]). relacion([sujeto(['Meta-analysis', of, genome, scans]), verbo([has]), complemento([yielded, loci, significant, for, lupus, 'patients,', one, of, which, includes, the, 'MHC', region])]). relacion([sujeto(['Regulatory', 'T', cells, are, immunoregulatory, cells, that]), verbo([modulate]), complemento([activated, immune, cells])]). relacion([sujeto(['Decreased', numbers, of, regulatory, 'T', cells]), verbo([have]), complemento([been, described, in, many, autoimmune, 'diseases,', including, systemic, lupus, erythematosus])]). relacion([sujeto(['Autoantibody', production, in, systemic, lupus, erythematosus, and, the, resulting, immune, complex, formation, and, complex, deposition, into, tissues, are, arguably, the, central, core, of, immune, dysregulation]), verbo([leading]), complemento([to, disease, manifestations, and, symptoms])]). relacion([sujeto(['Inability', of, the, immune, system, to]), verbo([recognize]), complemento([and, inhibit, autoreactive, immune, cells, in, this, particular, autoimmune, disease, may, be, the, result, of, inappropriate, numbers, and, function, of, regulatory, 'T', cells])]). relacion([sujeto(['Surprisingly,', our, findings, demonstrate, that, patients, from, the, local, 'Mississippi', area, exhibit]), verbo([increased]), complemento([proportions, of, 'CD25(+)', 'FoxP3(+)', regulatory, 'T', cells, and, 'CD25(+)', 'FoxP3(-)', 'T', cells, '(', of, 'CD45(+)', 'CD3(+)', 'CD4(+)', helper, 'T', 'cells)', as, compared, to, healthy, controls])]). relacion([sujeto(['Increased', gene, expression, of, 'FoxP3', together, with]), verbo([decreased]), complemento([gene, expression, levels, of, 'GATA3,', 'TNFAIP3,', and, 'TNFSF4', suggest, that, variations, in, gene, products, compared, to, healthy, controls, may, be, playing, a, role, in, the, immune, cell, dysregulation, and, disproportionate, 'CD25(+)', 'FoxP3(+)', regulatory, 'T', cells])]). relacion([sujeto(['The', frequencies, of, sneezing, and, scratching, were, significantly]), verbo([decreased]), complemento([by, pioglitazone, treatment, '(', 'P', &, 'lt;'])]). relacion([sujeto(['Eosinophils', infiltration, and, the, levels, of, 'interleukin-5', and, 'interferon-γ', in, nasal, cavity, lavage, fluid, and, sera, immunoglobulin, 'E', were, also, markedly]), verbo([decreased]), complemento([by, pioglitazone, '(', 'P', &, 'lt;'])]). relacion([sujeto(['The', expression, of, 'Foxp3', mRNA, and, the, population, of, 'Tregs', were, significantly]), verbo([increased]), complemento([by, pioglitazone, '(', 'P', &, 'lt;'])]). relacion([sujeto(['PPAR-γ', agonist, attenuates, upper, airway, allergic, inflammation, in, a, 'PPAR-γ-dependent', 'fashion,', and, the, beneficial, effects, of, pioglitazone, in, airway, allergic, inflammation, may, be]), verbo([mediated]), complemento([by, induction, of, 'Tregs'])]). relacion([sujeto(['They', were]), verbo([found]), complemento([expressed, at, high, level, in, 'thymus,', 'gill,', and, 'skin,', in, concert, with, the, transcription, factor, gene, 'GATA-3'])]). relacion([sujeto(['High', expression, levels, of, 'IL-4,', 'IL-13,', and, 'GATA-3', were, also, detected, in, murine, 'thymus,']), verbo([suggesting]), complemento([similar, importance, of, the, fish, and, mammalian, homologues, for, early, 'T', cell, development])]). relacion([sujeto(['The', mammalian]), verbo([target]), complemento([of, rapamycin, '(', 'mTOR)', controls, 'T-cell', differentiation, in, response, to, polarizing, cytokines])]). relacion([sujeto(['We', previously]), verbo([found]), complemento([that, mTOR, blockade, by, rapamycin, '(', 'RAPA)', delays, the, 'G1-S', cell, cycle, transition, and, lymphocyte, proliferation])]). relacion([sujeto(['Here,', we]), verbo([report]), complemento([that, both, mTOR, complex, 1, and, mTOR, complex, 2, are, readily, activated, following, 'TCR/CD28', engagement, and, are, critical, for, early, expression, of, 'Ifng,', 'Il4', and, 'Foxp3,', and, for, effector, 'T', cell, differentiation, in, the, absence, of, polarizing, cytokines])]). relacion([sujeto(['While', inhibition, of, mTOR, complex, 1, and, cell, division, were, evident, at, low, doses, of, 'RAPA,', inhibition, of, mTOR, complex, 2, ',', 'Ifng,', 'Il4', and, 'Foxp3', 'expression,', and, 'T-cell', polarization]), verbo([required]), complemento([higher, doses, and, more, prolonged, treatments])]). relacion([sujeto(['We']), verbo([found]), complemento([that, while, 'T-bet', and, 'GATA3', were, readily, induced, following, 'TCR/CD28', 'engagement,', administration, of, 'RAPA', delayed, their, 'expression,', and, interfered, with, the, loss, of, 'DNA', methylation, within, 'Ifng', and, 'Il4', promoter, regions])]). relacion([sujeto(['In', 'contrast,', 'RAPA']), verbo([prevented]), complemento(['activation-dependent', 'DNA', methylation, of, the, 'Foxp3', promoter, favoring, 'Foxp3', expression])]). relacion([sujeto(['We', propose, that, 'mTOR-signaling,', by, timing, the, expression, of, critical, transcription, factors, and, 'DNA', methylation, of, proximal, promoter, 'regions,']), verbo([regulates]), complemento([transcriptional, competence, at, immunologically, relevant, sites, and, hence, lymphocyte, differentiation])]). relacion([sujeto(['We']), verbo([report]), complemento([on, the, mRNA, levels, of, a, panel, of, transcription, factors, in, the, kidney, and, spleen, 'tissues,', and, in, the, cell, populations, from, the, 'blood,', the, 'spleen,', and, in, the, sorted, kidney, progenitor, cells])]). relacion([sujeto(['Splenocytes', and, 'PBLs', had, significantly, higher, mRNA, levels, of, the, transcription, factors]), verbo([involved]), complemento([in, myeloid, '(', pu])]). relacion([sujeto(['Furthermore,', the, 'R1', progenitor, cells, had, higher, mRNA, levels, of, the, transcription, factors]), verbo([involved]), complemento([in, early, progenitor, cells, '(', 'egr1,', 'gata2)', and, the, lymphoid, lineage, progenitors, '(', 'gata3,', 'pax5)', compared, to, those, in, kidney])]). relacion([sujeto(['Investigation', of, serotonergic, neuronal, activity, and, its, relationship, to, disease]), verbo([has]), complemento([been, limited, by, a, lack, of, physiologically, relevant, in, vitro, cell, models])]). relacion([sujeto(['Serotonergic', neurons, derived, from, embryonic, stem, cells, '(', 'ESCs)', could]), verbo([provide]), complemento([a, platform, for, such, studies, and, provide, models, for, use, in, drug, discovery])]). relacion([sujeto(['Here,', we]), verbo([report]), complemento([enhancement, of, serotonergic, differentiation, using, a, genetic, approach])]). relacion([sujeto(['Expression', of, 'Gata2']), verbo([increased]), complemento([the, yield, of, serotonergic, neurons])]). relacion([sujeto(['Enhancement', was, only, achieved, when, 'Gata2', was]), verbo([expressed]), complemento([under, the, control, of, the, 'tissue-specific', promoter, of, the, transcription, factor, 'Nkx6'])]). relacion([sujeto(['High', levels, of, 'Gata2', expression, in, 'ESCs', compromised, pluripotency, and]), verbo([induced]), complemento(['non-neuronal', differentiation])]). relacion([sujeto(['Combined', directed, expression, of, 'Gata2,', proneural, gene, 'Mash1,', and, forkhead, transcription, factor, 'Foxa2', further]), verbo([enhanced]), complemento([serotonergic, neural, 'differentiation,', resulting, in, a, 10, -, fold, increase, in, serotonin, content])]). relacion([sujeto(['The', presence, of, sonic, hedgehog, during, differentiation, produced, a, further, modest]), verbo([increase]), complemento([in, numbers, '(', 1.5, -, 'fold)'])]). relacion([sujeto(['Transgene', expression, did, not, influence, the, number, of, tyrosine, hydroxylase, positive, neurons, in, the, cultures, after, 20, 'days,', implying, that, 'Gata2,', 'Mash1,', and, 'Foxa2']), verbo([modulate]), complemento([in, vitro, differentiation, at, a, time, beyond, the, 'decision-point', for, dopaminergic, or, nondopaminergic, commitment])]). relacion([sujeto(['This', study, demonstrates, that, the, directed, expression, of, specific, transcription, factors]), verbo([enhances]), complemento([serotonergic, neuron, differentiation, in, vitro, and, highlights, the, importance, of, transgene, expression, at, the, right, stage, of, 'ESC', differentiation, to, effect, the, generation, of, a, desired, neural, subtype])]). relacion([sujeto(['Churg-Strauss', syndrome, '(', 'CSS)', is, a, rare, systemic, vasculitis]), verbo([associated]), complemento([with, eosinophilia, and, granuloma, formation])]). relacion([sujeto(['All', 'CSS', patients, had]), verbo([decreased]), complemento([percentage, of, 'FoxP3+', regulatory, 'T', cells])]). relacion([sujeto(['In', the, 'CSS/GC', group, we]), verbo([found]), complemento([an, increase, in, the, 'Th17/Treg', ratio, and, 'up-regulation', of, both, 'Th2', and, 'Th17', markers, as, evidenced, by, '(', 1, ')', over, expression, of, 'Th2-related', genes, '(', 'GATA3,', 'STAT6)', in, 'PBL,', '(', 2, ')', elevated, concentrations, of, serum, 'IL-5', and, 'CCL17,', and, '(', 3, ')', a, concomitant, increase, in, the, number, of, 'Th17', 'cells,', and, secretion, of, 'IL-17A', by, stimulated, 'PBL'])]). relacion([sujeto(['The', level, of, 'CCR4-active', chemokines, was]), verbo([increased]), complemento([in, 'active-CSS,', and, correlated, with, blood, eosinophilia])]). relacion([sujeto(['The', combined, treatment, with, steroids, and, other, immunosuppressive, drugs, was]), verbo([associated]), complemento([with, a, significant, decrease, in, both, 'Th2-related', chemokines, and, the, number, of, 'Th17', cells])]). relacion([sujeto(['Our', results, indicate, that, both, 'Th2', and, 'Th17', lineages, are]), verbo([involved]), complemento([in, the, pathogenesis, of, 'CSS,', while, 'CCR4-active', chemokines, contribute, to, eosinophilia, in, the, active, disease])]). relacion([sujeto(['These', phenomena, are, down]), verbo([regulated]), complemento([by, immunosuppressive, therapy])]). relacion([sujeto(['Forty-seven', individuals, with, allergic, asthma, and, 47, healthy, control, individuals]), verbo([provided]), complemento([5, &, 'nbsp;ml', of, anticoagulated, peripheral, venous, blood])]). relacion([sujeto(['CD4+', 'T', helper, '(', 'Th)', cells]), verbo([have]), complemento([been, divided, into, different, subsets, as, defined, by, their, cytokine, products, and, functions, after, their, activation])]). relacion([sujeto(['CD4+', 'T', cell, subsets, are, continuously, discovered, and, until, now, 'Th1,', 'Th2,', 'Th9,', 'Th17,', and, regulatory, 'T', '(', 'Treg)', cells]), verbo([have]), complemento([been, almost, unanimously, recognized, but, yet, not, completely, characterized])]). relacion([sujeto(['It', is, well, known, that, cytokines]), verbo([bind]), complemento([to, 'Type', 'I/II', cytokine, receptors, signaling, via, 'Janus', kinases, '(', 'JAKs)', followed, by, activation, of, 'Signal', 'Transducer', and, 'Activator', of, 'Transcription', '(', 'STAT)'])]). relacion([sujeto([')', also, controlled, by, 'cytokines,', in]), verbo([modulating]), complemento([the, 'Th', phenotype, and, functions])]). relacion([sujeto(['Expression', of, 'CD3d,', 'CD3z,', and, 'TRBC', '(', 'T-cell', receptor, beta, constant, 'region)', were]), verbo([associated]), complemento([with, the, immunohistological, diagnosis, of, inflammatory, cardiomyopathy, '(', 'DCMi)'])]). relacion([sujeto(['In', 'EMBs', from, 'DCM', patients, with]), verbo([increased]), complemento(['CD3d', 'expression,', significantly, increased, markers, of, 'Th1', '(', 'IFNγ,', 'T-bet,', 'Eomesodermin),', regulatory, 'T-cells', '(', 'Treg;', 'FoxP3,', 'TGFβ),', and, cytotoxic, 'T-cells', '(', 'CTLs:', 'Perforin,', 'Granulysin,', 'Granzyme', 'A)', were, 'present,', while, no, differential, polarization, of, 'T-cells', was, found, in, 'EMBs', form, 'AMC', patients])]). relacion([sujeto(['A', differential, dominance, of, distinct, functional, 'TRBV', families, was]), verbo([associated]), complemento([with, different, cardiotropic, 'viruses:', 'TRBV', 11, and, 24, with, 'Parvovirus', 'B19;', 'TRBV4,', 10, and, 28, with, human, herpes, virus, type, 6, ;, and, 'TRBV14', for, 'Coxsackie', 'virus,', respectively])]). relacion([sujeto(['The', 'virus-associated', differential, 'TRBV', dominance]), verbo([suggests]), complemento([an, antiviral, specificity, of, 'virus-induced', 'T-cell', responses, in, human, 'DCMi'])]). relacion([sujeto(['The', precise, nature, of, these, cues]), verbo([has]), complemento([not, been, fully, 'defined,', an, important, issue, given, that, 'EMT', is, an, early, event, in, tumor, metastasis])]). relacion([sujeto(['Here,', we]), verbo([have]), complemento([found, that, a, population, of, 'metastasis-prone', mouse, lung, adenocarcinoma, cells, expresses, 'Notch', and, 'Notch', ligands, and, that, the, 'Notch', ligand, 'Jagged2', promotes, metastasis])]). relacion([sujeto(['Mechanistically,', 'Jagged2', was]), verbo([found]), complemento([to, promote, metastasis, by, increasing, the, expression, of, 'GATA-binding', '(', 'Gata)', 'factors,', which, suppressed, expression, of, the, 'microRNA-200', '(', 'miR-200)', family, of, microRNAs, that, target, the, transcriptional, repressors, that, drive, 'EMT', and, thereby, induced, 'EMT'])]). relacion([sujeto(['Reciprocally,', 'miR-200']), verbo([inhibited]), complemento([expression, of, 'Gata3,', which, reversed, 'EMT', and, abrogated, 'metastasis,', suggesting, that, 'Gata3', and, 'miR-200', are, mutually, inhibitory, and, have, opposing, effects, on, 'EMT', and, metastasis])]). relacion([sujeto(['These', findings]), verbo([reveal]), complemento([what, we, believe, to, be, a, novel, 'Jagged2/miR-200-dependent', pathway, that, mediates, lung, adenocarcinoma, 'EMT', and, metastasis, in, mice, and, may, have, implications, for, the, treatment, of, human, epithelial, tumors])]). relacion([sujeto(['High-level']), verbo([nuclear]), complemento(['FOXA1', expression, was, seen, in, 19, '%', of, primary, and, 89, '%', of, metastatic, tumours, '(', 'P', &, 'lt;', 0.0001, ')'])]). relacion([sujeto(['Our', preliminary, analyses]), verbo([suggest]), complemento([that, 'high-level', 'FOXA1', expression, is, associated, with, the, development, of, metastatic, prostate, cancer])]). relacion([sujeto(['We']), verbo([report]), complemento([the, case, of, a, young, 'Emirati', boy, with, 'HDR', '(', 'Hypoparathyroidism,', sensorineural, 'Deafness,', and, 'Renal', 'hypoplasia)', syndrome, due, to, the, novel, heterozygous, deletion, of, two, nucleotides, '(', c])]). relacion([sujeto(['This', is, the, first, published]), verbo([report]), complemento([of, hypomagnesemia, in, association, with, 'HDR', syndrome])]). relacion([sujeto([',', mainly, secreting, 'TNF-α,', 'IL-4,', and, 'IL-13', and]), verbo([expressing]), complemento(['GATA-3'])]). relacion([sujeto(['MMP-2', degrades, the, type, 'I', 'IFN', 'receptor,', thereby]), verbo([preventing]), complemento(['STAT1', 'phosphorylation,', which, is, necessary, for, 'IL-12p35', production])]). relacion([sujeto(['Active', 'MMP-2,', 'therefore,']), verbo([acts]), complemento([as, an, endogenous, type, 2, &, 'quot;conditioner"', and, may, play, a, role, in, the, observed, prevalence, of, detrimental, type, 2, responses, in, melanoma])]). relacion([sujeto(['A', new, subset, of, 'CD4(+)', 'T', 'cells,', 'Th17,']), verbo([has]), complemento([been, recently, discovered, independent, from, 'Th1/Th2', paradigm])]). relacion([sujeto([5, ')', ',', and, 'IL-4', was]), verbo([increased]), complemento(['(', 'P<0'])]). relacion([sujeto(['Correspondingly,', the, expression, of, 'RORC', was]), verbo([decreased]), complemento([1.99, -, fold, '(', 'P<0'])]). relacion([sujeto([5, ')', ',', and, 'GATA-3', was]), verbo([increased]), complemento([1.76, -, fold, '(', 'P<0'])]). relacion([sujeto(['Moreover,', the, quantity, of, 'Th17', cells, in, peripheral, blood, was]), verbo([decreased]), complemento(['(', 'P<0'])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, 'Th17', cells, play, a, destructive, role, in, the, immune, balance, of, 'periodontitis,', and, the, effect, of, 'Th1', cells, is, not, 'significant,', while, 'Th2', cells, have, a, protective, effect])]). relacion([sujeto(['Transcription', factor, 'GATA-3', is, vital, for, multiple, stages, of, 'T', cell, and, natural, killer, '(', 'NK)', cell, 'development,', and, yet, the, factors, that, directly]), verbo([regulate]), complemento(['Gata3', transcription, during, hematopoiesis, are, only, marginally, defined])]). relacion([sujeto(['This', 'novel,', distant, element]), verbo([regulates]), complemento([multiple, major, developmental, stages, that, require, 'GATA-3', activity])]). relacion([sujeto(['Immune', reconstitution, inflammatory, syndrome, '(', 'IRIS)']), verbo([caused]), complemento([by, mycobacterium, in, patients, with, 'AIDS', is, often, experienced, in, clinical, practice])]). relacion([sujeto(['We', determined, the, immunopathological, characteristics, of, 'IRIS']), verbo([associated]), complemento([with, 'Mycobacterium', parascrofulaceum, infection, in, an, 'AIDS', patient])]). relacion([sujeto(['Portions', of, the]), verbo([involved]), complemento([lymph, nodes, and, lung, were, 'excised,', and, the, immunological, properties, were, analyzed, by, immunohistochemical, assays])]). relacion([sujeto(['Our', data]), verbo([provide]), complemento([the, first, evidence, to, reveal, the, status, of, the, axis, of, distinctive, immunity, in, the, process, of, granuloma, formation, caused, by, a, 'mycobacterium-related', infection])]). relacion([sujeto(['Neuro-Behçet\'s', 'Disease', '(', 'NBD)', is, hypothetically]), verbo([caused]), complemento([by, 'T', helper, '(', 'Th)', 'cells,', which, development, is, dependent, on, the, expression, of, 'lineage-specific', transcription, factors])]). relacion([sujeto(['Expression', of, 'TBX21', '(', 'Th1),', 'RORC', '(', 'Th17)', and, 'Foxp3', '(', 'Treg)', were]), verbo([increased]), complemento([in, 'NBD', patients, compared, to, 'HaBD', and, 'NIND', patients])]). relacion([sujeto(['EBI3', and, 'Th2-associated', 'GATA3', expressions, were]), verbo([found]), complemento([to, be, decreased, '(', 'P<0'])]). relacion([sujeto(['Analysis', of, transcription, factor, 'ratios,', revealed, an]), verbo([increase]), complemento([in, the, 'RORC/FOXP3', and, 'TBX21/GATA3', ratios, in, 'NBD', patients, '(', 'P<0'])]). relacion([sujeto(['Our', findings, indicate, that, both, 'Th1', and, 'Th17', mRNA, expressions]), verbo([involving]), complemento([a, possible, impairment, of, 'Treg', cells])]). relacion([sujeto(['The', 'TBX21/GATA3', and, 'RORC/FOXP3', ratios, dysregulations, in, 'NBD', are, consistent, with, those]), verbo([reported]), complemento([in, other, inflammatory, diseases, and, indicating, the, plasticity, existing, between, 'Th1,', 'Th17', and, 'Treg', cells, during, inflammation])]). relacion([sujeto(['Comparison', of, result, of, 'EBV', polypeptide, group, with, other, 3, different, cytokine]), verbo([stimulating]), complemento([groups, demonstrated, that, 'EBV', antigen, peptide, had, much, more, effects, on, stimulating, 'CTL', generation])]). relacion([sujeto(['The', expression, of, 'IFN-γ', gene, was, significantly, 'increased;', the, 'T', helper, 'differentiation-related', gene, 't-bet,', gata3, also]), verbo([increased]), complemento(['evidently,', while, expression, change, of, 'house-keeping', gene, mad1, and, pten, were, not, evident])]). relacion([sujeto(['Addition', of, different, cytokines, and, antigen, peptides, in, culture, may, be, much, more, effective, on]), verbo([stimulating]), complemento(['CTL', generation])]). relacion([sujeto(['GATA-3', is, necessary, for, the, development, of, 'MHC', class, 'II-restricted', 'CD4', 'T', 'cells,', and, its, expression, is]), verbo([increased]), complemento([during, positive, selection, of, these, cells])]). relacion([sujeto(['This', upregulation]), verbo([requires]), complemento([the, presence, of, the, transcription, factor, 'c-Myb'])]). relacion([sujeto(['Furthermore,', we, show, that, 'TH-POK', can, also, upregulate, 'GATA-3', in, 'double-positive', 'thymocytes,']), verbo([suggesting]), complemento([the, existence, of, a, positive, feedback, loop, that, contributes, to, lock, in, the, initial, commitment, to, the, 'CD4', lineage, during, differentiation])]). relacion([sujeto(['The', tyrosine, kinase, 2, variant, rs34536443]), verbo([has]), complemento([been, established, as, a, genetic, risk, factor, for, multiple, sclerosis, in, a, variety, of, populations])]). relacion([sujeto(['Furthermore,', we, assessed, the, functional, consequences, of, this, polymorphism, on, human, 'T', lymphocytes, by, comparing, the, reactivity, and, cytokine, profile, of, 'T', lymphocytes, isolated, from, individuals]), verbo([expressing]), complemento([the, protective, 'TYK2(GC)', genotype, with, the, 'disease-associated', 'TYK2(GG)', genotype])]). relacion([sujeto(['Our', results, demonstrate, that, the, protective, 'C', allele, infers]), verbo([decreased]), complemento([tyrosine, kinase, 2, 'activity,', and, this, reduction, of, activity, is, associated, with, a, shift, in, the, cytokine, profile, favouring, the, secretion, of, 'Th2', cytokines])]). relacion([sujeto(['These', findings]), verbo([suggest]), complemento([that, the, rs34536443, variant, effect, on, multiple, sclerosis, susceptibility, might, be, mediated, by, deviating, 'T', lymphocyte, differentiation, toward, a, 'Th2', phenotype])]). relacion([sujeto(['This', impact, of, tyrosine, kinase, 2, on, effector, differentiation, is, likely, to, be, of, wider, importance, because, other, autoimmune, diseases, also]), verbo([have]), complemento([been, associated, with, polymorphisms, within, tyrosine, kinase, 2])]). relacion([sujeto(['We']), verbo([found]), complemento([that, hypoxia, led, to, an, inhibition, of, differentiation, in, 'NK', 'cells,', and, increased, oxygen, supply, alleviated, this, inhibition, and, restored, 'NK', cell, differentiation, under, hypoxic, condition])]). relacion([sujeto(['Hypoxia-treated', cells, demonstrated, reduced, mRNA, expression, of, transcription, factors, '(', 'TFs)', that]), verbo([have]), complemento([important, roles, in, 'NK', cell, 'differentiation,', such, as, 'EOMES,', 'T-bet,', 'GATA-3', and, 'ETS-1'])]). relacion([sujeto(['Our', findings]), verbo([suggest]), complemento([that, oxygen, tension, modulates, in, vitro, differentiation, of, 'NK', cells, through, the, regulation, of, 'TF', expression])]). relacion([sujeto(['Neurons', differentiated, in, vitro, from, embryonic, stem, cells, '(', 'ESCs)']), verbo([have]), complemento([the, potential, to, serve, both, as, models, of, disease, states, and, in, drug, discovery, programs])]). relacion([sujeto(['We', then, 'investigate,', using, 'Ca(2+)', imaging, and, '[', '(', 3, ')', 'H]-GABA']), verbo([release]), complemento(['studies,', whether, the, 'GABAergic', neurons, produced, exhibit, distinct, functional, phenotypes])]). relacion([sujeto(['Forebrain', and, midbrain, 'GABAergic', neurons]), verbo([responded]), complemento([to, 'ATP', '(', 1, 'mM),', 'L-glutamate', '(', 30, 'μM),', noradrenaline, '(', 30, 'μM),', acetylcholine, '(', 30, 'μM)', and, dopamine, '(', 30, 'μM),', with, similar, elevations, of, intracellular, 'Ca(2+)([Ca(2+)](i))'])]). relacion([sujeto(['The', presence, of, 'GABA(A)', and, 'GABA(B)', 'antagonists,', bicuculline, '(', 30, 'μM)', and, 'CGP55845', '(', 1, 'μM),']), verbo([increased]), complemento([the, elevation, of, '[', 'Ca(2+)](i)', in, response, to, dopamine, '(', 30, 'μM)', in, 'midbrain,', but, not, forebrain, 'GABAergic', neurons])]). relacion([sujeto(['All', 'agonists,', except, 'dopamine,', elicited, similar, '[', '(', 3, ')', 'H]-GABA']), verbo([release]), complemento([from, forebrain, and, midbrain, cultures])]). relacion([sujeto(['Dopamine', '(', 30, 'μM)', did, not]), verbo([stimulate]), complemento([significant, '[', '(', 3, ')', 'H]-GABA', release, in, midbrain, 'cultures,', although, it, was, effective, in, forebrain, cultures])]). relacion([sujeto(['Prestin', is, the, motor, protein, of, the, outer, hair, cells, of, the, organ, of, 'Corti', and, a, key, factor, in]), verbo([ensuring]), complemento([a, high, level, of, sensitivity, of, mammalian, hearing])]). relacion([sujeto(['We', studied, the, effects, of, the, application, of, retinoic, 'acid,', a, ligand, of, a]), verbo([nuclear]), complemento(['receptor,', and, of, butyric, 'acid,', an, inhibitor, of, histone, deacetylase, 'activity,', on, the, expression, of, mRNA, of, prestin, and, 'Gata-3', in, the, organotypic, culture, of, the, organ, of, 'Corti', of, newborn, rats, using, 'RT-PCR'])]). relacion([sujeto(['Application', of, retinoic, acid, at, concentrations, of, 1, -, 50, μM, results, in, a, 'dose-dependent', expression]), verbo([decrease]), complemento([after, two, days, in, culture])]). relacion([sujeto(['The', data, indicate, that, retinoid]), verbo([nuclear]), complemento([transcription, 'factors,', 'GATA-3', and, histone, 'acetylation/deacetylation', processes, may, have, a, regulatory, role, to, play, in, prestin, expression])]). relacion([sujeto(['CD4(+)', 'T', cells, are, essential, for, defenses, against, pathogens, and, affect, the, functions, of, most, cells]), verbo([involved]), complemento([in, the, immune, response])]). relacion([sujeto(['Although', 'CD4(+)', 'T', cells, generally]), verbo([recognize]), complemento([peptide, antigens, bound, to, 'MHC-II', 'molecules,', important, subsets, are, restricted, by, other, 'MHC', or, 'MHC-like', 'molecules,', including, 'CD1d-restricted', &, 'quot;invariant"', iNK, 'T', cells])]). relacion([sujeto(['This', review, discusses, recently, identified, nodes, in, the, transcriptional, circuits, that, are]), verbo([involved]), complemento([in, controlling, 'CD4(+)', 'T-cell', 'differentiation,', notably, the, commitment, factor, 'Thpok', and, its, interplay, with, 'Runx', transcriptional, 'regulators,', and, focuses, on, how, transcription, factors, acting, upstream, of, 'Thpok,', including, 'Gata3,', 'Tox', and, 'E-box', 'proteins,', promote, the, emergence, of, 'CD4-lineage-specific', gene, expression, patterns])]). relacion([sujeto(['A', plasmacytoid, variant, of, urothelial, carcinoma]), verbo([has]), complemento([been, recently, recognized, in, the, 'World', 'Health', 'Organization', classification, system])]). relacion([sujeto(['Herein,', we]), verbo([report]), complemento([the, 'clinicopathologic,', 'immunohistochemical,', 'ultrastructural,', and, molecular, features, of, a, series, of, plasmacytoid, urothelial, carcinoma, of, the, urinary, bladder])]). relacion([sujeto(['Its', expression, is]), verbo([associated]), complemento([with, better, prognosis, and, disease, free, survival, in, breast, cancer, patients])]). relacion([sujeto(['Our', preliminary, results]), verbo([suggested]), complemento([that, 'GATA3', is, linked, to, the, 'ER'])]). relacion([sujeto(['This', scenario]), verbo([suggests]), complemento([that, 'GATA3', may, play, a, crucial, role, in, oestrogen, receptor, positive, breast, cancer, patients])]). relacion([sujeto(['Whether', 'GATA3', expression, is]), verbo([involved]), complemento([in, regulating, tumour, cell, growth, in, oestrogen, responsive, breast, cancer, is, a, key, question, that, remains, to, be, answered])]). relacion([sujeto(['Epigenetic', alteration, of, the, genome]), verbo([has]), complemento([been, shown, to, provide, palliative, effects, in, mouse, models, of, certain, human, autoimmune, diseases])]). relacion([sujeto(['We']), verbo([have]), complemento([investigated, whether, chromatin, remodeling, could, provide, protection, against, autoimmune, diabetes, in, 'NOD', mice])]). relacion([sujeto(['Protection', against, diabetes, was, accompanied, by, histone, hyperacetylation, in, pancreas, and, 'spleen,']), verbo([enhanced]), complemento([frequency, of, 'CD4(+)', 'CD62L(+)', cells, in, the, 'spleen,', reduction, in, cellular, infiltration, of, 'islets,', restoration, of, normoglycemia, and, 'glucose-induced', insulin, release, by, beta, cells])]). relacion([sujeto(['Activation', of, splenic, 'T', lymphocytes, derived, from, protected, mice, in, vitro, with, pharmacological, agents, that, bypass, the, antigen, receptor, or, immobilized, 'anti-CD3', antibody, resulted, in]), verbo([enhanced]), complemento([expression, of, 'Ifng', mRNA, and, protein, without, altering, the, expression, of, 'Il4,', 'Il17,', 'Il18,', 'Inos', and, 'Tnfa', genes, nor, the, secretion, of, 'IL-2,', 'IL-4,', 'IL-17', and, 'TNF-α', proteins])]). relacion([sujeto(['Consistently,', expression, of, the, transcription, factor]), verbo([involved]), complemento([in, 'Ifng', 'transcription,', 'Tbet/Tbx21', but, not, 'Gata3', and, 'Rorgt,', 'respectively,', required, for, the, transcription, of, 'Il4', and, 'Il17,', was, upregulated, in, activated, splenocytes, of, protected, mice])]). relacion([sujeto(['These', results, indicate, that, chromatin, remodeling, can]), verbo([lead]), complemento([to, amelioration, of, diabetes, by, using, multiple, mechanisms, including, differential, gene, transcription])]). relacion([sujeto(['Other', cytokines, known, for, their, role, in, inflammatory, processes, such, as, interleukin, 'IL-17', or, 'IL-18', as, well, as, factors, controlling, keratinocyte, differentiation, and, the, inflammatory, process, in, the, 'skin,', like, the, 'Notch', 'system,', could, also, be]), verbo([involved]), complemento([in, the, disease, outcome])]). relacion([sujeto(['Notch', receptors, are, a, group, of, transmembrane, proteins, that]), verbo([regulate]), complemento([cell, fate, decisions, during, development, and, adulthood, in, many, 'tissues,', including, keratinocyte, differentiation, and, 'T-cell', lineage, 'commitment,', depending, on, their, activation, by, specific, groups, of, ligands, '(', 'Delta-like', or, 'Jagged)'])]). relacion([sujeto(['To', compare, the, in, situ, expression, of, 'Notch', system, proteins, '(', 'receptors,', ligands, and, transcriptional, 'factors)', and, cytokines, possibly]), verbo([involved]), complemento([in, the, disease, outcome, '(', 'IL-17,', 'IL-18,', 'IL-23', and, transforming, growth, 'factor-β)', in, 'ATL', cutaneous, and, mucosal, 'lesions,', according, to, the, response, to, therapy, with, 'N-methyl', glucamine])]). relacion([sujeto(['Notch', receptors, and, 'Delta-like', ligands, were]), verbo([found]), complemento([increased, in, patients, with, 'ATL,', particularly, those, with, poor, response, to, therapy, or, with, mucosal, lesions])]). relacion([sujeto(['The']), verbo([increase]), complemento([of, 'Notch', receptors, and, 'Delta-like', ligands, in, patients, with, a, poor, response, to, treatment, suggests, that, these, patients, would, require, a, more, aggressive, therapeutic, approach, or, at, least, a, more, thorough, and, rigorous, 'follow-up'])]). relacion([sujeto(['An', altered, ratio, of, their, relative, expression]), verbo([promotes]), complemento([the, pathogenesis, of, certain, immunological, 'diseases,', but, whether, this, may, also, contribute, to, the, pathogenesis, of, 'antibody-mediated', rejection, '(', 'ABMR)', versus, 'T', 'cell-mediated', rejection, '(', 'TCMR)', is, unknown])]). relacion([sujeto(['We']), verbo([found]), complemento([a, predominant, intraglomerular, expression, of, 'T-bet', in, patients, with, 'ABMR,', which, was, distinct, from, that, in, patients, with, 'TCMR'])]). relacion([sujeto(['The', expression, of, intraglomerular, 'T-bet', correlated, with, infiltration, of, 'CD4+', and, 'CD8+', 'lymphocytes,', which]), verbo([express]), complemento(['T-bet,', as, well, as, intraglomerular, 'CD68+', 'monocyte/macrophages,', which, do, not, express, 'T-bet'])]). relacion([sujeto(['The', predominance, of, intraglomerular, 'T-bet', expression, relative, to, 'GATA3', expression]), verbo([associated]), complemento([with, poor, response, to, treatment, with, bolus, steroid])]). relacion([sujeto(['Glucosamine']), verbo([has]), complemento([been, shown, to, have, immunosuppressive, 'properties,', but, its, effect, on, 'AD', has, not, been, examined])]). relacion([sujeto(['To', determine, the, mechanism]), verbo([associated]), complemento([with, inhibition, of, the, 'Th2', immune, 'response,', the, effects, of, glucosamine, on, the, selective, differentiation, pathway, of, the, 'Th', subset, in, vitro, was, examined, in, 'NC/Nga', mice])]). relacion([sujeto(['The', results, showed, that, glucosamine]), verbo([suppressed]), complemento([the, differentiation, of, naïve, 'CD4(+)', 'T', cells, to, 'Th2', cells, in, vitro])]). relacion([sujeto(['The', production, of, 'Th2', 'cytokines,', such, as, 'IL-4', and, 'IL-5,', was, significantly]), verbo([decreased]), complemento([after, in, vitro, administration, of, 'glucosamine,', which, suggest, that, glucosamine, might, be, a, useful, immunomodulatory, agent, for, the, treatment, of, human, 'AD'])]). relacion([sujeto(['Mounting', evidence, from, animal, models]), verbo([has]), complemento([demonstrated, that, alterations, in, 'T-cell', receptor, '(', 'TCR)', signaling, alone, can, lead, to, dramatically, skewed, differentiation, of, naive, 'T', cells, into, 'T(H)2', 'cells,', to, 'T(H)2', effector, 'functions,', and, to, 'T(H)2-related', diseases])]). relacion([sujeto(['Specifically,', a, number, of, immunodeficiencies]), verbo([associated]), complemento([with, atopic, disease, might, have, atopy, as, a, manifestation, because, of, aberrant, 'TCR', signaling])]). relacion([sujeto(['Th1', cells]), verbo([have]), complemento([been, implicated, as, the, causal, agents, in, the, pathogenesis, of, autoimmunity])]). relacion([sujeto(['Copy', number, variations, '(', 'CNVs)']), verbo([have]), complemento([been, discovered, to, have, phenotypic, consequences, and, associate, with, various, types, of, diseases])]). relacion([sujeto(['CNVs', of, 'IL-12B', and, 'T-bet', are]), verbo([associated]), complemento([with, the, risk, of, 'SLE'])]). relacion([sujeto(['To', investigate, the, effect, of, 'Astragalus', in]), verbo([regulating]), complemento([the, imbalance, between, naive, helper, 'T', cells, '(', 'Th1/Th2)', cytokines, expression, in, patients, with, cervical, cancer])]). relacion([sujeto(['After', 'AI', 'treatment,', the, lowered, parameters, were, 'up-regulated', '(', 'P', &, 'lt;', 0.05, ')', ',', and, no, obvious, change, was, observed, in, the, 'CD4+', 'IL-4', positive, cell]), verbo([associated]), complemento([parameters])]). relacion([sujeto(['Th1/Th2', cell, function, imbalance, existed, in, patients, with, cervical, 'cancer,', showing, a, 'Th2', predominant, reaction, 'mode;', 'AI', can]), verbo([regulate]), complemento([the, 'imbalance,', offset, to, 'Th1,', thus, to, display, its, 'anti-tumor', effect])]). relacion([sujeto(['High', resolution, melting, '(', 'HRM)', curve, analysis, represents, a, 'fast,', 'post-PCR', 'high-throughput', method, for, scanning, somatic, sequence, alterations, in]), verbo([target]), complemento([genes])]). relacion([sujeto(['Paraffin-embedded', samples]), verbo([require]), complemento([higher, quantity, of, purified, 'DNA', for, high, performance])]). relacion([sujeto(['T', helper, cell, differentiation, and, activation]), verbo([require]), complemento([specific, transcriptional, programs, accompanied, by, changes, in, chromatin, structure])]). relacion([sujeto(['We']), verbo([found]), complemento([that, binding, of, the, remodeling, protein, 'BRG1', was, programmed, by, both, lineage, and, activation, signals])]). relacion([sujeto(['BRG1']), verbo([binding]), complemento([positively, correlated, with, gene, activity, at, 'protein-coding', and, microRNA, '(', 'miRNA)', genes])]). relacion([sujeto(['BRG1']), verbo([binding]), complemento([was, found, at, promoters, and, distal, 'regions,', including, both, novel, and, previously, validated, distal, regulatory, elements])]). relacion([sujeto(['Distal', 'BRG1']), verbo([binding]), complemento([correlated, with, 'expression,', and, novel, distal, sites, in, the, 'Gata3', locus, possessed, 'enhancer-like', 'activity,', suggesting, a, general, role, for, 'BRG1', in, 'long-distance', gene, regulation])]). relacion([sujeto(['BRG1', recruitment, to, distal, sites, in, 'Gata3', was, impaired, in, cells, lacking, 'STAT6,', a, transcription, factor, that]), verbo([regulates]), complemento(['lineage-specific', genes])]). relacion([sujeto(['Together,', these, findings]), verbo([suggest]), complemento([that, 'BRG1', interprets, both, differentiation, and, activation, signals, and, plays, a, causal, role, in, gene, 'regulation,', chromatin, 'structure,', and, cell, fate])]). relacion([sujeto(['Our', findings]), verbo([suggest]), complemento([that, 'BRG1', binding, is, a, useful, marker, for, identifying, active, 'cis-regulatory', regions, in, 'protein-coding', and, miRNA, genes])]). relacion([sujeto(['Interleukin-10', was, originally, described, as, a, factor, that]), verbo([inhibits]), complemento([cytokine, production, by, murine, 'Th1', clones])]). relacion([sujeto(['Recent', studies]), verbo([have]), complemento([since, shown, that, 'IL-10', can, also, downregulate, 'Th2', clones, and, their, production, of, 'IL-4', and, 'IL-5'])]). relacion([sujeto(['Because', of, its, 'immuno-suppressive', 'properties,', 'IL-10']), verbo([has]), complemento([been, suggested, as, a, potential, therapy, for, allergic, inflammation, and, asthma])]). relacion([sujeto(['However,', the, pathophysiological, role, of, 'IL-10', in, vivo]), verbo([has]), complemento([not, been, clearly, elucidated])]). relacion([sujeto(['When', 'GATA-3/TCR-Tg', mice, sensitized, with, 'OVA', and, alum, were, injected, with, 'C57-IL-10', cells, before, 'OVA', 'inhalation,', the, levels, of, 'IL-5,', 'IL-13,', and, 'IL-4']), verbo([decreased]), complemento([by, 40, -, 85, '%', and, number, of, eosinophils, decreased, by, 70, '%', '(', 'P<0'])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, 'IL-10', plays, an, important, role, downstream, of, the, inflammatory, cascade, in, the, 'Th2', response, to, antigens, and, in, the, development, of, 'BALF', eosinophilia, and, cytokine, production, in, a, murine, model, of, asthma])]). relacion([sujeto(['Gastric', adenocarcinoma, is, a, major, health, problem, 'world-wide,', as, this, is, the, second, most, common]), verbo([cause]), complemento([of, cancer, death, in, the, world])]). relacion([sujeto(['It']), verbo([has]), complemento([been, estimated, that, infection, by, 'Helicobacter', pylori, cause, at, least, half, of, the, gastric, cancers])]). relacion([sujeto(['Previously,', we]), verbo([have]), complemento([demonstrated, that, 'H'])]). relacion([sujeto([pylori, antigens, directly]), verbo([activate]), complemento(['NK', cells, to, secrete, 'IFN-γ'])]). relacion([sujeto(['There', is, also, a, marked, synergistic, effect, in, 'NK', cells]), verbo([stimulated]), complemento([with, bacterial, lysate, and, low, levels, of, 'IL-12,', a, cytokine, which, is, produced, by, macrophages, and, dendritic, cells, in, the, 'H'])]). relacion([sujeto(['The', present, study, was, designed, to, investigate, whether, 'NK', cells, from, gastric, cancer, patients, display, an, altered, ability, to]), verbo([respond]), complemento([to, components, from, 'H'])]). relacion([sujeto(['The', results, show, that, 'NK', cells, from, peripheral, blood, of, gastric, cancer, patients]), verbo([have]), complemento([a, severely, suppressed, ability, to, produce, 'IFN-γ', after, stimulation, with, 'H'])]). relacion([sujeto(['Furthermore,', the, synergistic, effect, of, 'IL-12', and, lysate, is, absent, in, gastric, cancer, 'patients,', unless, the, concentration, of, 'IL-12', is]), verbo([increased]), complemento([10, -, fold])]). relacion([sujeto(['In', 'addition,', we, propose, that, the, observed, suppression, is, due, to, 'tumour-derived', 'TGF-β', and, that]), verbo([increased]), complemento([expression, of, the, transcription, factor, 'GATA-3', may, be, responsible, for, the, 'TGF-β', induced, suppression])]). relacion([sujeto(['Those', mRNA, transcripts, that, are]), verbo([expressed]), complemento([at, two, distinct, abundances, in, proportion, to, 'SNP', allele, frequency, may, warrant, further, study])]). relacion([sujeto(['Although', much, research]), verbo([has]), complemento([been, conducted, to, investigate, the, expression, of, 'MMP1', in, many, different, cell, types, and, 'conditions,', the, regulation, of, its, expression, is, still, not, fully, understood])]). relacion([sujeto(['In', this, 'study,', we, used, a, novel, but, straightforward, method, based, on, agglomerative, hierarchical, clustering, to, identify, bimodally]), verbo([expressed]), complemento([transcripts, in, human, umbilical, vein, endothelial, cell, '(', 'HUVEC)', microarray, data, from, 15, individuals])]). relacion([sujeto(['We']), verbo([found]), complemento([that, 'MMP1', mRNA, abundance, was, bimodally, distributed, in, 'un-treated', 'HUVECs', and, showed, a, bimodal, response, to, inflammatory, mediator, treatment])]). relacion([sujeto(['Chromatin', immunoprecipitation, '(', 'ChIP)', experiments, indicated, that, the, transcription, factors, '(', 'TFs)', 'ETS1,', 'ETS2', and, 'GATA3,']), verbo([bind]), complemento([to, the, 'MMP1', promoter, in, the, region, of, this, polymorphism, and, may, contribute, to, the, bimodal, expression])]). relacion([sujeto(['We', describe, a, simple, method, to, identify, putative, bimodally]), verbo([expressed]), complemento(['RNAs', from, transcriptome, data, that, is, effective, yet, easy, for, 'non-statisticians', to, understand, and, use])]). relacion([sujeto(['GATA3', mutations]), verbo([cause]), complemento(['HDR', '(', 'hypoparathyroidism,', sensorineural, 'deafness,', and, renal, 'dysplasia)', syndrome, 'and,', consistent, with, the, presence, of, the, second, 'DiGeorge', syndrome, locus, '(', 'DGS2)', proximal, to, 'GATA3,', distal, 10, p, deletions, often, leads, to, 'HDR', and, 'DiGeorge', syndromes])]). relacion([sujeto(['Here,', we]), verbo([report]), complemento([on, six, 'Japanese', patients, with, 'GATA3', abnormalities])]). relacion([sujeto(['Deletion', analysis, of, chromosome, 10, p, revealed]), verbo([loss]), complemento([of, 'GATA3', and, preservation, of, 'D10S547', in, case, 6])]). relacion([sujeto(['The', results, are, consistent, with, the, previous]), verbo([finding]), complemento([that, 'GATA3', mutations, are, usually, identified, in, patients, with, two, or, three, of, the, 'HDR', triad, 'features,', and, provide, supportive, data, for, the, mapping, of, 'DGS2', in, the, region, proximal, to, 'D10S547'])]). relacion([sujeto(['Indeed,', reciprocal, 'membrane-bond', 'IL-15', 'trans-presentation', commits, these, cells, into, 'NK', 'differentiation,', while, 'membrane-bound', 'IL-15', stimulation, with, its, soluble, ligand, '(', 'sIL-15Rα)']), verbo([triggers]), complemento([a, reverse, signal, '(', 'pERK1/2', and, 'pFAK)', that, modifies, the, developmental, program, of, at, least, two, subsets, of, 'PB-NKPs'])]). relacion([sujeto(['The', generation, of, these, putative, 'NK/DCs', is]), verbo([associated]), complemento([to, the, rapid, inhibition, of, negative, regulators, of, myelopoiesis, '(', the, transcription, factors, 'STAT6', and, 'GATA-3)', followed, by, the, transient, upregulation, of, inducers, of, myeloid, 'development,', such, as, the, transcription, factors, '(', 'PU'])]). relacion([sujeto(['Functional', noradrenergic, transmission]), verbo([requires]), complemento([the, coordinate, expression, of, enzymes, involved, in, norepinephrine, '(', 'NE)', 'synthesis,', as, well, as, the, norepinephrine, transporter, '(', 'NET)', which, removes, 'NE', from, the, synapse])]). relacion([sujeto(['Inflammatory', cytokines]), verbo([acting]), complemento([through, gp130, can, suppress, the, noradrenergic, phenotype, in, sympathetic, neurons])]). relacion([sujeto(['For', 'example,', cytokines]), verbo([suppress]), complemento([noradrenergic, function, in, sympathetic, neurons, after, axotomy, and, during, heart, failure])]). relacion([sujeto(['Chromatin', immunoprecipitation, experiments, revealed, that, 'Phox2a', did, not]), verbo([bind]), complemento([the, 'NET', 'promoter,', and, overexpression, of, 'Phox2a', did, not, prevent, cytokine, suppression, of, 'NET', transcription])]). relacion([sujeto(['Hand2', and, 'Gata3', are, transcription, factors, that]), verbo([induce]), complemento([noradrenergic, genes, during, development, and, are, present, in, mature, sympathetic, neurons])]). relacion([sujeto(['Both', 'Hand2', and, 'Gata3', were]), verbo([decreased]), complemento([by, cytokines, in, sympathetic, neurons, and, neuroblastoma, cells])]). relacion([sujeto(['NET', and, 'Hand2', mRNAs]), verbo([decreased]), complemento([significantly, in, sympathetic, neurons, 48, h, after, 'axotomy,', but, 'Gata3', mRNA, was, unchanged])]). relacion([sujeto(['These', data]), verbo([suggest]), complemento([that, cytokines, can, inhibit, 'NET', expression, through, downregulation, of, 'Hand2', or, 'Gata3', in, cultured, sympathetic, 'neurons,', but, axotomy, in, adult, animals, selectively, suppresses, 'Hand2', expression])]). relacion([sujeto(['Selective', breeding]), verbo([has]), complemento([been, employed, to, improve, resistance, to, infectious, diseases, in, aquaculture, and, it, is, of, importance, to, investigate, the, expression, profiles, of, immune, genes, together, with, complement, activity, of, 'Atlantic', salmon, with, different, genetic, background, in, response, to, 'pathogens,', in, particular, against, 'Aeromonas', salmonicida])]). relacion([sujeto(['The', results, showed, that, the, expression, pattern, of]), verbo([target]), complemento([genes, differed, in, lymphoid, and, 'non-lymphoid', organs, in, the, two, families])]). relacion([sujeto(['One', may, speculate, that, a, relatively, high, immune, response, is, a, 'pre-requisite', for]), verbo([increased]), complemento([survival, in, a, 'A'])]). relacion([sujeto(['Complement', activity, may, be, applied, as, an, indicator, in, selective, breeding, for]), verbo([enhanced]), complemento([disease, resistance])]). relacion([sujeto(['recently,', molecular, subclassification, of, breast, carcinomas]), verbo([has]), complemento([been, proposed, as, a, new, prognostic, parameter])]). relacion([sujeto(['GATA3', positivity, was]), verbo([associated]), complemento([with, low, grade, tumors, and, luminal, 'A', subtype])]). relacion([sujeto(['GATA3', expression, was]), verbo([associated]), complemento([with, luminal, 'A', and, low, histological, grade])]). relacion([sujeto(['Clinical', data]), verbo([suggest]), complemento([that, the, estrogen, receptor, '(', 'ER)', contributes, to, chemotherapeutic, responsiveness])]). relacion([sujeto(['In', this, 'study,', we, used, a, microarray, approach, to]), verbo([find]), complemento([novel, 'ER-related', genes, that, predicted, chemotherapy, 'responses,', with, the, hope, of, providing, a, robust, 'multi-variable', prediction, method])]). relacion([sujeto(['A', total, of, 55, training, cases, were, used, for, marker, discovery, and, for, identification, of, any, 'ER-related', genes, that, may]), verbo([have]), complemento([been, associated, with, a, chemotherapeutic, response, '(', &, 'quot;training', 'cases")'])]). relacion([sujeto(['In', the, training, 'set,', 20, significantly, differentially]), verbo([expressed]), complemento([genes, were, identified])]). relacion([sujeto(['Among', these, 20, 'genes,', 'TFF1,', 'ESR1,', 'GATA3', and, 'TFF3', were]), verbo([found]), complemento([to, be, 'ER-related'])]). relacion([sujeto(['Among', 55, independent, validation, 'cases,', univariate, analysis, indicated, that, clinical, variables, and, 'ER-related', genes, were, all, significantly]), verbo([associated]), complemento([with, pCR])]). relacion([sujeto(['In', conjunction, with, levels, of, 'ER-related', 'genes,', expression, of, 'ER', protein, may]), verbo([provide]), complemento([important, predictive, outcomes, for, responses, to, neoadjuvant, chemotherapy, and, may, allow, for, the, identification, of, a, subgroup, of, patients, who, could, significantly, benefit, from, chemotherapy, '(', or, who, may, be, resistant, to, 'it)'])]). relacion([sujeto(['We']), verbo([have]), complemento([previously, shown, that, the, in, vitro, embryonic, development, and, the, yield, of, viable, calves, were, increased, by, using, a, 'two-step', chemically, defined, medium, for, 'post-fertilization', culture, of, bovine, embryos])]). relacion([sujeto(['In', this, 'study,', we, explored, the, embryonic, development, and, the, temporal, behavioral, interaction, of, the, genes]), verbo([involved]), complemento([in, 'IFNτ', gene, expression, and, how, they, behave, in, an, orchestrated, manner, to, increase, the, developmental, competence, of, 'IVF', produced, embryos, by, culturing, in, the, chemically, defined, medium])]). relacion([sujeto(['Early', embryonic, development, was]), verbo([found]), complemento([to, be, better, in, 'two-step', chemically, defined, culture, system, than, that, of, mSOF, as, indicated, by, the, increment, of, blastocyst, 'yield,', 33.1, '%', in, 'two-step', culture, system, vs, 18.8, '%', in, mSOF, 'medium,', and, the, blastocyst, 'hatching,', 52.3, '%', in, 'two-step', culture, system, vs, 33.5, '%', in, mSOF, medium])]). relacion([sujeto(['Relative', quantitative, gene, expression, showed, harmonic, behavior, in, the, 'two-step', culture, system, rather, than, the, culture, in, 'mSOF,', 'IFNτ', showed, even]), verbo([increase]), complemento([throughout, the, embryonic, development, in, the, 'two-step', culture, medium, while, it, decreased, with, blastocyst, hatching, in, mSOF, culture, condition])]). relacion([sujeto(['Temporal', dominance, of, 'OCT4', over, all, the, transcription, factors, was]), verbo([found]), complemento([in, regulation, of, 'IFNτ', expression, '(', the, major, factor, of, expression, regulation, but, in, inverse, 'manner)'])]). relacion([sujeto(['CDX2', directly, related, with, 'IFNτ,', but, still, under, 'OCT4', dominance, and, also]), verbo([regulated]), complemento([by, the, subservient, of, 'OCT4', which, is, 'NANOG'])]). relacion([sujeto(['In', 'conclusion,', this, study, confirmed, our, previous, results, about, the, usefulness, of, using, the, 'two-step', chemically, defined, culture, medium, for]), verbo([increasing]), complemento([the, developmental, competence, of, 'IVF', produced, embryos, and, elucidated, the, dominance, of, 'OCT4', over, the, other, genes, implicated, in, regulation, of, 'IFNτ', expression])]). relacion([sujeto(['Together,', these, data, indicate, that, a, strong, inflammatory, and, 'Th1', response, occurs, after, highly, pathogenic, avian, influenza, infection, in, the, chicken, that]), verbo([has]), complemento([implications, for, strategies, that, target, the, immune, system, for, improving, resistance, to, avian, influenza])]). relacion([sujeto(['DN1', cells]), verbo([retain]), complemento([the, ability, to, become, natural, killer, 'cells,', dendritic, 'cells,', 'B', 'cells,', and, myeloid, cells, as, well, as, 'T', 'cells,', but, these, options, are, lost, by, the, 'DN3', stage])]). relacion([sujeto(['Previously,', we, discovered, that, the, 'E-protein', transcription, factor, 'HEBAlt']), verbo([promoted]), complemento(['T-cell', specification])]). relacion([sujeto(['Here,', we]), verbo([report]), complemento([that, 'HEB(-/-)', 'T-cell', precursors, have, compromised, 'Notch1', function, and, lose, 'T-cell', potential])]). relacion([sujeto(['However,', instead, of, becoming, 'B', 'cells,', 'HEB(-/-)', 'DN3', cells, adopted, a, 'DN1-like', phenotype, and, could, be]), verbo([induced]), complemento([to, differentiate, into, thymic, 'NK', cells])]). relacion([sujeto(['HEB(-/-)', 'DN1-like', cells]), verbo([retained]), complemento(['GATA3', and, 'Id2', expression, but, had, lower, levels, of, the, 'Bcl11b', 'gene,', a, 'Notch', target, gene])]). relacion([sujeto(['Therefore,', our, studies]), verbo([have]), complemento([revealed, a, new, set, of, interactions, between, 'HEB,', 'Notch1,', and, 'GATA3', that, regulate, the, 'T-cell', fate, choice, in, developing, thymocytes])]). relacion([sujeto(['Obesity']), verbo([causes]), complemento([insulin, resistance, in, target, tissues, -, skeletal, 'muscle,', adipose, 'tissue,', liver, and, the, brain])]). relacion([sujeto(['Neuronatin', '(', 'Nnat)', expression]), verbo([has]), complemento([been, found, to, be, altered, in, a, number, of, conditions, related, to, inflammatory, or, metabolic, 'disturbance,', but, its, physiological, roles, and, regulatory, mechanisms, in, adipose, 'tissue,', 'brain,', pancreatic, islets, and, other, tissues, are, not, understood])]). relacion([sujeto(['We', identified, transcription, factor]), verbo([binding]), complemento([sites, '(', 'TFBS)', conserved, in, the, 'Nnat', 'promoter,', and, transcription, factors, '(', 'TF)', abundantly, expressed, in, adipose, tissue])]). relacion([sujeto(['We', identified, 'KEGG', pathways, significantly]), verbo([associated]), complemento([with, 'Nnat', 'expression,', including, positive, correlations, with, inflammation, and, negative, correlations, with, metabolic, pathways, '(', most, prominently, oxidative, 'phosphorylation,', glycolysis, and, 'gluconeogenesis,', pyruvate, 'metabolism)', and, protein, turnover])]). relacion([sujeto([27, 'genes,', 'including;', 'Gstt1', and, 'Sod3,', concerned, with, oxidative, 'stress;', 'Sncg', and, 'Cxcl9', concerned, with, 'inflammation;', 'Ebf1,', 'Lgals12', and, 'Fzd4']), verbo([involved]), complemento([in, 'adipogenesis;', whose, expression, 'co-varies', with, 'Nnat', were, 'identified,', and, conserved, transcription, factor, binding, sites, identified, on, their, promoters])]). relacion([sujeto(['Cho-kyung-jong-ok-tang', '(', 'CKJOT)', is, a, traditional, 'Korean', herbal, formula, specifically, used, for, female, infertility, including, unexplained, recurrent, pregnancy]), verbo([loss]), complemento(['(', 'RPL)'])]). relacion([sujeto(['However,', 'CKJOT', addition, during, 'NK', cell, differentiation]), verbo([suppressed]), complemento([the, production, of, 'interferon-gamma', '(', 'IFN-γ),', and, enhanced, that, of, 'interleukin-5,', in, the, 'NK1', and, 'NK2', 'subsets,', respectively])]). relacion([sujeto(['T-bet,', a, transcription, factor]), verbo([associated]), complemento([with, 'IFN-γ', expression, was, 'down-regulated;', while, 'Th2', linked, transcription, factors, '(', 'STAT6', and, 'GATA3)', were, 'up-regulated', especially, with, 100, 'μg/mL', treatment, of, 'CKJOT'])]). relacion([sujeto(['The', type, 2, shift, in, 'NK', 'cell-secreted', cytokines]), verbo([induced]), complemento([by, 'CKJOT', in, mouse, 'NK', cells, may, explain, the, protective, effect, associated, with, its, traditional, use, in, unexplained, 'RPL'])]). relacion([sujeto(['We', previously, showed, that, 'APRIL']), verbo([suppressed]), complemento(['Th2', cytokine, production, in, cultured, 'CD4(+)', 'T', cells, and, 'Th2', antibody, responses])]). relacion([sujeto(['Here', we, show, that, 'APRIL']), verbo([suppresses]), complemento([allergic, lung, 'inflammation,', which, is, associated, with, diminished, expression, of, the, transcription, factor, 'c-maf'])]). relacion([sujeto(['Likewise,', blockade, of, 'APRIL', in, 'WT', mice, by, the, 'APRIL-receptor', fusion, 'protein,', transmembrane, activator, and, calcium, modulator, and, cyclophilin, ligand, interactor, '(', 'TACI)-Ig,']), verbo([enhanced]), complemento([lung, inflammation])]). relacion([sujeto(['Mechanistically,', the, expression, of, the, 'Th2', cytokine, transcription, factor, 'c-maf,', but, not, 'GATA-3,', was, markedly]), verbo([enhanced]), complemento([in, 'April(-/-)', 'CD4(+)', 'T', cells, at, the, 'RNA', and, protein, level, and, under, 'non-polarizing', '(', 'Th', 'neutral,', 'ThN)', and, 'Th2-polarizing', conditions])]). relacion([sujeto(['Since', 'c-maf', transactivates, the, 'IL-4', 'gene,', the]), verbo([increased]), complemento(['c-maf', expression, in, 'April(-/-)', mice, readily, explains, increased, 'Th2', cytokine, production])]). relacion([sujeto(['Independent', of, its, effect, on, 'IL-4,', 'APRIL']), verbo([suppressed]), complemento(['IL-13', expression])]). relacion([sujeto(['APRIL', thus, may]), verbo([regulate]), complemento([lung, inflammation, in, a, dual, 'way,', by, acting, on, 'c-maf', expression, and, by, directly, controlling, 'IL-13', production])]). relacion([sujeto(['Umbilical', cord, tissue, is]), verbo([gained]), complemento([attention, as, a, novel, source, of, multipotent, stem, cells, because, it, is, easily, 'obtainable,', ethically, acceptable, and, the, cells, are, immunologically, naïve])]). relacion([sujeto(['In', this, 'study,', we]), verbo([have]), complemento([isolated, and, characterized, a, new, cell, type, expressing, 'MUCIN1', '(', 'CD227)', from, human, umbilical, cord, lining, which, we, termed, 'MUCIN-expressing', 'Cord', 'Lining', 'Epithelial', 'Cell', '(', 'CLEC-muc)'])]). relacion([sujeto(['We']), verbo([found]), complemento([that, 'CLEC-muc', is, highly, proliferative, and, had, significant, clonogenic, ability])]). relacion([sujeto(['These', cells]), verbo([express]), complemento([embryonic, stem, cell, markers, 'OCT-4,', 'NANOG,', 'SSEA-4,', 'REX1', and, 'SOX2'])]). relacion([sujeto(['We']), verbo([found]), complemento([that, 'BMP4', does, not, alter, cytoplasmic, expression, of, p63, that, promotes, cell, proliferation])]). relacion([sujeto(['However,', it]), verbo([increases]), complemento([nuclear, p63, expression, together, with, several, other, 'epithelial-associated', genes, such, as, 'GATA3,', 'JAGGED1,', 'NOTCH1,', 'HES1', and, 'IKKα'])]). relacion([sujeto(['BMP4']), verbo([has]), complemento([also, been, found, to, weakly, induce, deltaNp63, expression, in, 'CLEC-muc'])]). relacion([sujeto(['Our', results]), verbo([suggest]), complemento([that, 'CLEC-muc', is, a, novel, stem, 'cell-like', population, that, can, be, further, differentiated, by, 'BMP4', to, generate, specific, 'cell-types', probably, destined, to, form, 'non-keratinized', epithelia])]). relacion([sujeto(['To', study, the, actions, of, transcription, 'factors,', 'T-bet', and, 'GATA-3,', and, their, relevant, signal, transduction, pathways, on, the, 'immune-related', pathogenesis, with, chronic, aplastic, anemia, '(', 'CAA),', and, to, investigate, the, immunological, regulation, mechanism, of, 'Shengxue', 'Mixture', '(', 'SXM)', in]), verbo([regulating]), complemento([levels, of, 'Th', cell, 'imbalance,', transcriptional, factor, and, relevant, signal, pathways])]). relacion([sujeto(['Florfenicol']), verbo([has]), complemento([been, shown, to, possess, 'anti-inflammatory', activity])]). relacion([sujeto(['However,', its, possible, use, for, asthma]), verbo([has]), complemento([not, yet, been, studied])]). relacion([sujeto(['Treatment', with, florfenicol]), verbo([caused]), complemento([a, marked, reduction, in, inflammatory, cells, and, three, 'Th2', type, cytokines, in, the, bronchoalveolar, lavage, fluids, of, mice])]). relacion([sujeto(['Histological', studies, using, 'H&E', and, 'AB-PAS', staining, demonstrate, that, florfenicol, substantially]), verbo([inhibited]), complemento(['ovalbumin-induced', inflammatory, cells, infiltration, in, lung, tissue, and, goblet, cell, hyperplasia, in, the, airway])]). relacion([sujeto(['Our', results]), verbo([suggested]), complemento([that, the, protective, effect, of, florfenicol, was, mediated, by, the, inhibition, of, the, p38, 'MAPK-mediated', phosphorylation, of, 'GATA', 3])]). relacion([sujeto(['Growing', evidence]), verbo([has]), complemento([suggested, that, two, 'Th1/Th2-specific', transcription, 'factors,', 'T-bet', and, 'GATA-3,', may, play, a, critical, role, in, the, development, of, 'Th1', and, 'Th2', immunity])]). relacion([sujeto(['In', 'mammals,', 'IL-21', is, a, common, γ, chain, cytokine, produced, by]), verbo([activated]), complemento(['CD4(+)', 'T', cells, and, 'NKT', cells, that, acts, on, multiple, lineages, of, cells])]). relacion([sujeto(['Although', 'IL-21']), verbo([has]), complemento([also, been, discovered, in, 'birds,', 'amphibians,', and, 'fish,', to, 'date,', no, functional, studies, have, been, reported, for, any, nonmammalian, 'IL-21', molecule])]). relacion([sujeto(['We']), verbo([have]), complemento([sequenced, an, 'IL-21', gene, '(', 'tIL-21)', in, rainbow, 'trout,', which, has, a, 'six-exon/five-intron', 'structure,', is, expressed, in, immune, 'tissues,', and, is, induced, by, bacterial, and, viral, infection, and, the, 'T', cell, stimulant, 'PHA'])]). relacion([sujeto(['In', contrast, to, 'mammals,', calcium, ionophore, and, 'PMA']), verbo([act]), complemento([synergistically, to, induce, 'tIL-21'])]). relacion([sujeto(['Recombinant', 'tIL-21', '(', 'rtIL-21)']), verbo([induced]), complemento([a, rapid, and, 'long-lasting', '(', 4, -, 72, 'h)', induction, of, expression, of, 'IFN-γ,', 'IL-10,', and, 'IL-22,', signature, cytokines, for, 'Th1-,', 'Th2-,', and, 'Th17-type', 'responses,', 'respectively,', in, head, kidney, leukocytes])]). relacion([sujeto(['rtIL-21']), verbo([maintained]), complemento([the, expression, of, 'CD8α,', 'CD8β,', and, 'IgM', at, a, late, stage, of, stimulation, when, their, expression, was, significantly, decreased, in, controls, and, increased, the, expression, of, the, 'Th', cell, markers, 'CD4,', 'T-bet,', and, 'GATA3'])]). relacion([sujeto(['Intraperitoneal', injection, of, 'rtIL-21', confirmed, the, in, vitro, bioactivity, and]), verbo([increased]), complemento([the, expression, of, 'IFN-γ,', 'IL-10,', 'IL-21,', 'IL-22,', 'CD8,', and, 'IgM'])]). relacion([sujeto(['This', study, helps, to, clarify, the, role, of, 'IL-21', in, lower, vertebrates, for, the, first, 'time,', to, our, 'knowledge,', and]), verbo([suggests]), complemento(['IL-21', is, a, likely, key, regulator, of, 'T', and, 'B', cell, function, in, fish])]). relacion([sujeto(['Regulatory', 'T', cells, '(', 'Tregs)']), verbo([have]), complemento([been, suggested, to, be, deeply, associated, with, immune, tolerance, and, 'long-term', graft, survival, in, transplantation])]). relacion([sujeto(['However,', effective, assays, for, assessing, the, suitability, of, patients]), verbo([have]), complemento([yet, to, be, established])]). relacion([sujeto(['Heterozygous', 'GATA3', abnormalities, are]), verbo([associated]), complemento([with, 'hypoparathyroidism,', sensorineural, 'deafness,', and, renal, abnormality, '(', 'HDR', 'syndrome)'])]). relacion([sujeto(['We']), verbo([report]), complemento([the, clinical, phenotypes, and, the, molecular, analysis, of, 'GATA3', in, five, 'Japanese', 'HDR', 'patients,', including, two, familial, cases])]). relacion([sujeto(['Sequence', analysis, of, 'GATA3', demonstrated, three, novel, '(', 'R262G,', c1063delC, and, 'C318)', and, two]), verbo([reported]), complemento([mutations, '(', c])]). relacion([sujeto(['Transient', transfection, assay, using, the, 'GATA3']), verbo([activating]), complemento([reporter, system, revealed, that, the, transactivating, activity, of, the, 'R262G,', c])]). relacion([sujeto(['Atoh1', null, mice, die, at, birth, and]), verbo([have]), complemento([some, undifferentiated, cells, in, sensory, epithelia, carrying, 'Atoh1', markers])]). relacion([sujeto(['Using', in, situ, hybridization, we]), verbo([find]), complemento([that, 'Tg(Pax2-Cre)', recombines, the, floxed, 'Atoh1', prior, to, detectable, 'Atoh1', expression])]). relacion([sujeto(['Only', the, posterior, canal, crista]), verbo([has]), complemento(['Atoh1', expressing, hair, cells, due, to, incomplete, recombination])]). relacion([sujeto(['However,', some, of, the, remaining, organ, of, 'Corti', cells]), verbo([express]), complemento(['Myo7a', at, late, postnatal, stages, and, are, innervated, by, remaining, afferent, fibers])]). relacion([sujeto(['Afferents', focus, their, projections, on, patches, that]), verbo([express]), complemento([the, prosensory, specifying, 'gene,', 'Sox2'])]). relacion([sujeto(['This', pattern, of, innervation, by, sensory, neurons, is]), verbo([maintained]), complemento([at, least, until, 'P14,', but, fibers, target, the, few, 'Myo7a', positive, cells, found, in, later, stages])]). relacion([sujeto(['Peroxisome', 'proliferator-activated', receptor, gamma, '(', 'PPAR-gamma)', agonists]), verbo([have]), complemento([been, shown, to, be, involved, in, the, regulation, of, allergic, inflammatory, responses])]). relacion([sujeto(['The', molecular, mechanisms, by, which, 'PPAR-gamma', activation]), verbo([inhibits]), complemento([the, inflammatory, process, have, not, been, well, understood])]). relacion([sujeto(['The', frequencies, of, sneezing, and, 'nose-scratching', and, eosinophil, infiltration]), verbo([decreased]), complemento([significantly, in, the, 'PIO', treatment, group, compared, with, the, 'OVA', group, '(', p, &, 'lt;', 0.05, ')'])]). relacion([sujeto(['PIO', significantly]), verbo([increased]), complemento([the, expression, of, 'Foxp3', mRNA, '(', p, &, 'lt;', 0.05, ')', and, induced, production, of, regulatory, 'T', lymphocyte, '(', p, &, 'lt;', 0.01, ')', compared, with, the, 'OVA', group])]). relacion([sujeto(['Balb/C', mice, were, submitted, to, the, 'co-induction', of, experimental, 'PD', '(']), verbo([induced]), complemento([by, 'Actinobacillus', actinomycetemcomitans, oral, 'inoculation)', and, 'AL', '[', induced, by, sensitization, with, ovalbumin, '(', 'OVA)', and, the, subsequent, 'OVA', 'challenges],', and, evaluated, regarding, 'PD', and, 'AL', 'severity,', immune, response, '[', cytokine, production, at, periodontal, 'tissues,', and, 'T-helper', transcription, factors, in, submandibular, lymph, nodes, '(', 'LNs)]', and, infection, parameters])]). relacion([sujeto(['PD/AL', 'co-induction']), verbo([decreased]), complemento(['PD', alveolar, bone, loss, and, periodontal, inflammation, while, experimental, 'AL', parameters, were, unaltered])]). relacion([sujeto(['An', active, functional, interference, was, 'verified,', because, independent, 'OVA', sensitization, and, challenge, not]), verbo([modulate]), complemento(['PD', outcome])]). relacion([sujeto(['PD+AL', group, presented]), verbo([decreased]), complemento([tumour, necrosis, 'factor-α', '(', 'TNF-α),', interleukin, '(', 'IL)-1β,', 'interferon-γ,', 'IL-17A,', receptor, activator, of, nuclear, factor, 'κ-light-chain-enhancer', of, activated, 'B', cells, ligand, and, matrix, metalloproteinase, '(', 'MMP)-13', levels, in, periodontal, 'tissues,', while, 'IL-4', and, 'IL-10', levels, were, unaltered, by, 'AL', 'co-induction'])]). relacion([sujeto([our, results, demonstrate, that, the, interaction, between, experimental, periodontitis, and, allergy]), verbo([involves]), complemento([functional, immunological, 'interferences,', which, restrains, experimental, periodontitis, development, by, means, of, a, skewed, immune, response])]). relacion([sujeto(['Acute', ethanol, intoxication]), verbo([has]), complemento([the, potential, to, alter, immune, reactivity, by, various, pathways])]). relacion([sujeto(['Following', 'LPS', 'challenge,', gene, expression, of, 'Foxp3', 'increased,', whereas, 'RORγt']), verbo([decreased]), complemento([after, 3, 'hours,', 'GATA3', decreased, within, 1, 'hour,', whereas, expression, of, 'T-bet', did, not, change, at, any, time])]). relacion([sujeto(['Ethanol']), verbo([suppressed]), complemento([the, 'LPS-induced', gene, expression, of, 'Foxp3,', 'RORγt,', and, 'T-bet', after, 8, 'hours,', expression, of, 'TNF-α', and, 'IFN-γ', was, also, suppressed, after, 3, and, 8, hours])]). relacion([sujeto(['Our', results, indicate, that, 'HS2', is, the]), verbo([target]), complemento([of, 'GATA-3', in, regulating, chromosomal, modification, of, the, 'Il4', locus, and, is, independent, of, the, 'Il5', and, 'Il13', loci])]). relacion([sujeto(['The', study, was, aimed, to, explore, the, effects, of, 'T-bet', '(', 'T-box']), verbo([expressed]), complemento([in, 'T', 'cell),', 'GATA-3(GATA', binding, protein, 3, ')', and, relevant, signal, transduction, pathways, on, the, 'immune-related', pathogenesis, of, chronic, aplastic, anemia, '(', 'CAA),', and, to, investigate, the, immunological, regulation, mechanism, in, the, treatment, of, 'CAA', by, using, cyclosporine, 'A', '(', 'CsA)', at, the, level, of, 'Th', cell, 'imbalance,', transcriptional, 'factors,', and, relevant, signal, pathways])]). relacion([sujeto(['CsA', lowers, the, abnormal, activation, of, 'IFN-γ/T-bet', and, 'IL-12/STAT4', pathways, to, correct, 'Th1', 'hyperpolarization,', which, may, reduce, the, abnormally]), verbo([activated]), complemento(['cell-mediated', immunity, and, relax, hematopoietic, depression, of, 'AA', patients])]). relacion([sujeto(['HDR', syndrome, is, an, autosomal, dominant, disorder, characterized, by, 'hypoparathyroidism,', sensorineural, 'deafness,', and, renal, anomaly]), verbo([caused]), complemento([by, mutation, of, the, 'GATA3', gene, located, at, chromosome, 10, p15])]). relacion([sujeto(['We']), verbo([report]), complemento([the, case, of, a, neonate, with, 'HDR', syndrome, and, a, novel, 'GATA3', mutation])]). relacion([sujeto(['Mutated', and, 'wild-type', 'GATA3', proteins, were]), verbo([expressed]), complemento([at, a, similar, level, in, 'vitro,', indicating, that, the, mutated, 'GATA3', protein, was, stable])]). relacion([sujeto(['Luciferase', assay, revealed, that, the, 'Cys321Ser-mutated', 'GATA3', lacked, transactivation, activity, due, to]), verbo([loss]), complemento([of, 'DNA-binding', activity, as, confirmed, by, gel, shift, assay])]). relacion([sujeto(['These', findings, indicate, that, not, only, haploinsufficiency, of, 'GATA3', but, also, the, 'dominant-negative', effect, of, 'Cys321Ser-mutated', 'GATA3', might]), verbo([have]), complemento([been, responsible, for, the, 'HDR', syndrome, phenotype, of, our, patient])]). relacion([sujeto(['Serum', total, 'IgE', was, 'measured,', and, peripheral, blood, mononuclear, cells, '(', 'PBMCs)', were, isolated, and]), verbo([stimulated]), complemento([in, vitro, with, 'anti-CD3/anti-CD28,', followed, by, mRNA, isolation])]). relacion([sujeto(['Elderly', asthmatic, patients]), verbo([have]), complemento([lower, 'FoxP3', mRNA, expression, in, 'PBMC,', which, can, be, associated, with, the, sustained, inflammatory, process, and, with, the, decreased, immune, tolerance, by, 'Treg', cells])]). relacion([sujeto(['The', 'T-bet', deficiency, and, the, correlation, of, 'GATA-3', expression, with, the]), verbo([increase]), complemento([of, 'IgE', are, characteristics, of, 'long-lasting', asthma])]). relacion([sujeto(['Changes', related, to, the, immunosenescence, process, could]), verbo([provide]), complemento([an, explanation, for, the, minor, differences, observed, between, the, groups])]). relacion([sujeto(['Over', the, past, 'years,']), verbo([increasing]), complemento([numbers, of, distinct, subsets, have, been, discovered, and, identified, for, a, 'T', 'lymphocytes\'', entity])]). relacion([sujeto(['Next,', we]), verbo([provide]), complemento([evidences, for, the, direct, interplay, of, 'Runx1/3', with, 'T-bet', and, 'GATA3', during, 'Th1', versus, 'Th2', commitment, to, activate, or, silence, transcription, of, signature, cytokine, 'genes,', 'IFNγ', and, 'IL4'])]). relacion([sujeto(['The', 'GATA', family, members, are, zinc, finger, transcription, factors]), verbo([involved]), complemento([in, cell, differentiation, and, proliferation])]). relacion([sujeto(['GATA3', in, particular, is, necessary, for, mammary, gland, 'maturation,', and, its]), verbo([loss]), complemento([has, been, implicated, in, breast, cancer, development])]). relacion([sujeto(['We']), verbo([associated]), complemento(['GATA3', expression, with, patient, outcomes, and, clinicopathologic, variables])]). relacion([sujeto(['Expression', of, 'GATA3', was, significantly]), verbo([increased]), complemento([in, breast, 'cancer,', in, situ, 'lesions,', and, hyperplastic, tissue, compared, with, normal, breast, tissue])]). relacion([sujeto(['GATA3', expression]), verbo([decreased]), complemento([with, increasing, tumor, grade])]). relacion([sujeto(['In', 'addition,', low, 'GATA3', expression, correlated, with]), verbo([increased]), complemento([tumor, size, and, estrogen, and, progesterone, receptor, negativity])]). relacion([sujeto(['This']), verbo([finding]), complemento([has, been, validated, in, a, diverse, set, of, populations])]). relacion([sujeto(['Thus,', 'GATA3', expression]), verbo([has]), complemento([utility, as, a, prognostic, indicator, in, breast, cancer])]). relacion([sujeto(['The', 'Src', family, kinase, 'Lck', is, thought, to, facilitate, 'Th2', 'differentiation;', 'however,', its, role, in, 'Th1', cells]), verbo([has]), complemento([not, been, well, explored])]). relacion([sujeto(['Using', mice, that, lack, 'Lck', in, mature, 'T', 'cells,', we]), verbo([find]), complemento([that, 'lck(-/-)', 'Th1', skewed, cells, have, normal, expression, of, 'T-bet', and, produce, 'IFN-γ', at, 'WT', levels])]). relacion([sujeto(['However,', there, is, a, 3, -, fold]), verbo([increase]), complemento([in, 'IL-10', producing, cells, in, the, mutant, cultures])]). relacion([sujeto(['These', cells, do, not]), verbo([have]), complemento([elevated, levels, of, 'IL-4,', 'GATA3,', 'IL-17', or, 'Foxp3,', indicating, that, they, are, not, 'Th2,', 'Th17,', or, 'Foxp3(+)', 'T', regulatory, cells, '(', 'Treg)'])]). relacion([sujeto(['These', data, highlight, a, previously, unappreciated, role, for, 'Lck', in]), verbo([regulating]), complemento(['IL-10', in, 'Th1', cells])]). relacion([sujeto(['Previously,', we]), verbo([found]), complemento([that, gene, expression, in, histologically, normal, breast, epithelium, '(', 'NlEpi)', from, women, at, high, breast, cancer, risk, can, resemble, gene, expression, in, 'NlEpi', from, 'cancer-containing', breasts])]). relacion([sujeto(['We', identified, 198, genes, that, are, differentially]), verbo([expressed]), complemento([between, 'NlEpi', from, breasts, with, 'ER+', '(', 'NlEpiER+)', compared, with, 'ER-', cancers, '(', 'NlEpiER-)'])]). relacion([sujeto(['NlEpi', gene, expression, may, help, elucidate, 'subtype-specific', risk, 'signatures,', identify, early, genomic, events, in, cancer, 'development,', and, locate]), verbo([targets]), complemento([for, prevention, and, therapy])]). relacion([sujeto(['Using', the, sequence, motif, analysis, environment, 'iMotifs,', we, identified, predicted]), verbo([binding]), complemento([sites, for, four, of, the, 10, 'TFs', '(', 'GATA6,', 'GATA3,', 'TCF7L2', and, 'MAF)', in, the, 'miR-302', cluster, promoter, region])]). relacion([sujeto(['Cord', blood, 'IgE', '(', 'CBIgE)', is, a]), verbo([recognized]), complemento([risk, factor, for, the, subsequent, development, of, allergic, diseases])]). relacion([sujeto(['In', contrast, with, numerous, genetic, studies, of, total, serum, 'IgE', in, children, and, 'adults,', limited, genetic, studies, on, 'CBIgE']), verbo([have]), complemento([been, conducted])]). relacion([sujeto(['To', test, the, associations, between, functional, or, tagging, single, nucleotide, polymorphisms, '(', 'SNPs)', in, genes]), verbo([involved]), complemento([in, the, 'T(H)1/T(H)2', pathway, and, 'CBIgE', in, a, large, 'US', 'inner-city', birth, cohort])]). relacion([sujeto(['Three', 'SNPs', '(', 'rs1800925,', 'rs2069743,', and, 'rs1295686)', in, the, 'IL13', gene, were, significantly]), verbo([associated]), complemento([with, 'CBIgE', concentration, '(', 'P', '≤', 6, ×, 10, '(', -, 4, ')', ',', 'FDR-corrected', 'P', &, 'lt;'])]). relacion([sujeto(['Our', data, demonstrated, that, multiple, 'SNPs', were, individually, and, jointly]), verbo([associated]), complemento([with, 'CBIgE,', with, evidence, of, 'gene-gene', interactions, and, ethnic, heterogeneity])]). relacion([sujeto(['These', findings]), verbo([suggest]), complemento([that, genetic, regulation, of, 'IgE', may, begin, in, utero])]). relacion([sujeto(['Furthermore,', we, confirmed, the, role, of, the, major, histocompatibility, complex, in, disease, etiology, by]), verbo([revealed]), complemento([a, strong, human, leukocyte, antigen, '(', 'HLA)', association, '(', 'rs6903608,', 'OR', =, 1.7, ',', combined, 'P', =, 2.84, ×, 10, '(', -, 50, ')', ')'])]). relacion([sujeto(['These', data]), verbo([provide]), complemento([new, insight, into, the, pathogenesis, of, cHL])]). relacion([sujeto(['Although', previously, regarded, as, being]), verbo([required]), complemento([only, during, early, 'T', cell, 'development,', recent, studies, demonstrate, an, important, role, for, 'TCF-1', in, 'T', helper, 2, '(', 'Th2)', cell, polarization])]). relacion([sujeto(['TCF-1', was, shown, to]), verbo([activate]), complemento([expression, of, the, 'Th2', transcription, factor, 'GATA-binding', protein, 3, '(', 'GATA3)', and, thus, to, promote, the, development, of, 'IL-4-producing', 'Th2', cells, independent, of, 'STAT6', signaling])]). relacion([sujeto(['The', 'down-regulation', is, largely, due, to, the, polarizing, cytokine, 'IL-4', because, 'IL-4', alone, is, sufficient, to, substantially]), verbo([inhibit]), complemento(['TCF-1', expression])]). relacion([sujeto(['The', 'IL-4-induced', suppression, of, 'TCF-1', is]), verbo([mediated]), complemento([by, 'STAT6,', as, shown, by, electrophoretic, mobility, shift, 'assays,', chromatin, 'immunoprecipitation,', and, 'STAT6', knockdown, experiments])]). relacion([sujeto(['Moreover,', we]), verbo([found]), complemento([that, 'IL-4/STAT6', predominantly, inhibits, the, 'shorter,', 'dominant-negative', 'TCF-1', 'isoforms,', which, were, reported, to, inhibit, 'IL-4', transcription])]). relacion([sujeto(['Thus,', this, study]), verbo([provides]), complemento([a, model, for, an, 'IL-4/STAT6-dependent', fine, tuning, mechanism, of, 'TCF-1-driven', 'T', helper, cell, polarization])]). relacion([sujeto(['Somatic', cell]), verbo([nuclear]), complemento([transfer, '(', 'NT)-specific', effects, on, postblastocyst, early, cattle, embryogenesis, were, investigated, by, comparison, to, in, 'vitro-produced', '(', 'IVP)', embryos, grown, under, identical, conditions, to, embryonic, days, '(', 'E)', 14, and, 15])]). relacion([sujeto(['A', developmental, expression, profile, was, determined, for, nine, trophoblast, 'markers,', two, inner, cell, mass, '(', 'ICM)/epiblast', 'markers,', and, 'E-cadherin', at, nine, time, points, between, 'E7', and, 'E26,']), verbo([providing]), complemento([a, molecular, gene, signature, assay, for, developmental, progression])]). relacion([sujeto(['Furthermore,', the, average, residual, deviation, of, all, 10, genes, did, not, differ, significantly]), verbo([suggesting]), complemento([an, overall, &, 'quot;normality"', in, gene, expression, of, 'E14/15', 'NT', embryos])]). relacion([sujeto(['GATA', family, transcription, factors, play, multiple, vital, roles, in, hematopoiesis, in, many, cell, 'lineages,', and, in, 'particular,', 'T', cells]), verbo([require]), complemento(['GATA-3', for, execution, of, several, developmental, steps])]). relacion([sujeto(['GATA-3']), verbo([has]), complemento([been, described, as, a, master, regulator, of, 'T-helper', 2, '(', 'Th2)', cell, differentiation, in, mature, 'CD4(+)', 'T', cells])]). relacion([sujeto(['In', 'contrast,', its, importance, prior, to, 'β-selection']), verbo([has]), complemento([been, obscured, both, by, the, developmental, heterogeneity, of, double, negative, '(', 'DN)', 1, thymocytes, and, the, paucity, of, early, 'T-lineage', progenitors, '(', 'ETPs),', a, subpopulation, of, 'DN1', cells, that, contains, the, most, immature, thymic, progenitors, that, retain, potent, 'T-lineage', developmental, potential])]). relacion([sujeto(['By', examining, multiple, lines, of, in, vivo, evidence, procured, through, the, analysis, of, 'Gata3', mutant, 'mice,', we]), verbo([have]), complemento([recently, demonstrated, that, 'GATA-3', is, additionally, required, at, the, earliest, stage, of, thymopoiesis, for, the, development, of, the, 'ETP', population])]). relacion([sujeto(['Here,', we, review, the, characterized, functions, of, 'GATA-3', at, each, stage, of, 'T-cell', development, and, discuss, hypothetical, molecular, pathways, that]), verbo([mediate]), complemento([these, functions])]). relacion([sujeto(['The', transcriptional, networks, that]), verbo([regulate]), complemento([these, fate, choices, are, composed, of, both, common, and, 'lineage-specific', 'components,', which, combine, to, create, a, cellular, context, that, informs, the, developmental, response, to, external, signals])]). relacion([sujeto(['E', proteins, are, an, important, factor, during, 'lymphopoiesis,', and, 'E2A', in, particular, is]), verbo([required]), complemento([for, normal, 'T-', and, 'B-cell', development])]). relacion([sujeto(['Although', the, other, 'E', 'proteins,', 'HEB', and, 'E2-2,', are]), verbo([expressed]), complemento([during, lymphopoiesis, and, can, compensate, for, some, of, 'E2A\'s', 'activity,', 'E2A', proteins, have, 'non-redundant', functions, during, early, 'T-cell', development, and, at, multiple, checkpoints, throughout, 'B', lymphopoiesis])]). relacion([sujeto(['More', 'recently,', a, role, for, 'E2A']), verbo([has]), complemento([been, demonstrated, in, the, generation, of, 'lymphoid-primed', multipotent, progenitors, and, shown, to, favor, their, specification, toward, lymphoid, over, myeloid, lineages])]). relacion([sujeto(['The', two, complexes, analyzed, focused, on, the]), verbo([nuclear]), complemento([proteins, 'Bmi-1', and, 'GATA3', that, were, expressed, within, the, cells, at, low, and, high, 'levels,', respectively])]). relacion([sujeto(['The']), verbo([increase]), complemento([in, the, number, of, identified, proteins, was, especially, pronounced, for, the, 'Bmi-1', 'complex,', where, the, target, protein, was, expressed, at, a, low, level])]). relacion([sujeto(['The', data, show, that, prefractionation, of, affinity, isolated, protein, complexes, using, 'SCX', prior, to, 'LC-MS/MS', analysis, significantly]), verbo([increases]), complemento([the, number, of, identified, proteins, and, individual, protein, 'coverage,', particularly, for, target, proteins, expressed, at, low, levels])]). relacion([sujeto(['Polycomb', group, '(', 'PcG)', and, trithorax, group, '(', 'TrxG)', complexes, exert, opposing, effects, on, the, maintenance, of, the, transcriptional, status, of, the, developmentally]), verbo([regulated]), complemento(['Hox', genes])]). relacion([sujeto(['In', this, 'study,', we, show, that, activation, of, 'STAT6']), verbo([induces]), complemento([displacement, of, the, 'PcG', complex, by, the, 'TrxG', complex, at, the, upstream, region, of, the, gene, encoding, 'GATA3,', a, transcription, factor, essential, for, 'T', helper, type, 2, '(', 'Th2)', cell, differentiation])]). relacion([sujeto(['Once', 'Th2', cells, 'differentiate,', 'TrxG', complex]), verbo([associated]), complemento([with, the, 'TrxG', component, 'Menin', binds, to, the, whole, 'GATA3', gene, 'locus,', and, this, binding, is, required, for, the, 'long-term', maintenance, of, expression, of, 'GATA3', and, 'Th2', cytokine])]). relacion([sujeto(['Naturally', occurring, regulatory, 'T', '(', 'nTreg)', cells]), verbo([express]), complemento(['Foxp3', and, were, originally, discovered, as, immune, suppressors, critical, for, 'self-tolerance', and, immune, homeostasis])]). relacion([sujeto(['Particularly,', attenuation, of, 'Foxp3', expression]), verbo([led]), complemento([to, 'Th2', conversion, of, nTreg, cells, in, vivo])]). relacion([sujeto(['We']), verbo([found]), complemento([that, 'wild-type', nTreg, cells, expressing, reduced, levels, of, 'Foxp3', but, not, those, expressing, no, 'Foxp3', produced, the, 'Th2', cytokine, 'IL-4'])]). relacion([sujeto(['Intriguingly,', 'IL-4', production, by, converted, nTreg, cells, is]), verbo([required]), complemento([for, 'Th2', differentiation, of, coexisting, naive, 'CD4', 'T', cells, in, 'vivo,', suggesting, that, 'Th2', conversion, of, nTreg, cells, might, be, critical, for, directing, 'Th2', immune, responses])]). relacion([sujeto(['Indeed,', compared, with, naive, 'CD4', 'T', 'cells,', nTreg]), verbo([expressed]), complemento([elevated, levels, of, 'GATA-3', independent, of, 'STAT-6'])]). relacion([sujeto(['And', 'GATA-3', was]), verbo([required]), complemento([for, 'nTreg-to-Th2', conversion])]). relacion([sujeto(['Foxp3', may, account, for, this, 'GATA-3', upregulation, in, nTreg, 'cells,', because, ectopic, expression, of, 'Foxp3', preferentially]), verbo([promoted]), complemento(['GATA-3', but, not, 'T-bet', expression])]). relacion([sujeto(['Thus,', we]), verbo([have]), complemento([identified, an, intrinsic, mechanism, that, imposes, a, 'Th2/Th1', imbalance, and, predisposes, 'Foxp3-expressing', cells, to, 'IL-4', production, independent, of, 'STAT-6', signaling])]). relacion([sujeto(['The', imbalance, between, regulatory, 'T', cells, '(', 'Treg)', and, effector, 'T', cells, is, important, for]), verbo([maintaining]), complemento([of, psoriasis, vulgaris])]). relacion([sujeto(['Data', show, that, tacrolimus]), verbo([has]), complemento([multiple, impacts, on, 'FOXP3,', but, the, exact, pharmacological, mechanism, of, tacrolimus, on, 'FOXP3', have, yet, to, be, elucidated])]). relacion([sujeto(['We', herein]), verbo([suggest]), complemento([the, bidirectional, immunoregulation, of, tacrolimus, on, 'FOXP3'])]). relacion([sujeto(['High', concentration, of, tacrolimus, renders, the, cooperation, of, 'NFAT', with, 'STAT6', and, 'NF-κB', to]), verbo([activate]), complemento(['GATA3', transcription])]). relacion([sujeto(['On', the, 'contrary,', low, concentration, of, tacrolimus, results, in, higher, nucleus, level, of, 'NFAT,', which, directly]), verbo([binds]), complemento([to, 'FOXP3', enhancer, 'and/or', cooperates, with, 'Smad3', to, activate, 'FOXP3', transcription])]). relacion([sujeto(['Further', studies, using]), verbo([loss]), complemento([of, function, and, 'over-expression', methods, are, needed, to, determine, the, detailed, molecules, involved, in, this, bidirectional, immunoregulation, of, tacrolimus, on, 'FOXP3'])]). relacion([sujeto(['Dietary', zinc, supplementation, may, help, to]), verbo([promote]), complemento(['growth,', boost, the, immune, 'system,', protect, against, 'diabetes,', and, aid, recovery, from, diarrhoea])]). relacion([sujeto(['We', exploited, the, zebrafish, '(', 'Danio', 'rerio)', gill, as, a, unique, vertebrate, ion, transporting, epithelium, model, to, study, the, 'time-dependent', regulatory, networks, of, 'gene-expression']), verbo([leading]), complemento([to, homeostatic, control, during, zinc, supplementation])]). relacion([sujeto(['Fish', were]), verbo([maintained]), complemento([with, either, zinc, supplemented, water, '(', 4.0, 'μM)', and, diet, '(', 2023, mg, zinc, 'kg-1)', or, water, and, diet, containing, 'Zn2+', at, 0.25, μM, and, 233, mg, zinc, 'kg-1,', respectively])]). relacion([sujeto(['The', number, of]), verbo([regulated]), complemento([genes, increased, up, to, day, 7, but, declined, as, the, fish, acclimated])]). relacion([sujeto(['In', total, 525, genes, were]), verbo([regulated]), complemento(['(', having, a, 'fold-change', more, than, 1.8, fold, change, and, an, adjusted, 'P-value', less, than, 0.1, which, is, controlling, a, 10, '%', 'False', discovery, 'rate,', 'FDR)', by, zinc, 'supplementation,', but, little, overlap, was, observed, between, genes, regulated, at, successive, 'time-points'])]). relacion([sujeto(['The', results]), verbo([suggest]), complemento([that, zinc, supplementation, reactivated, developmental, pathways, in, the, gill, and, stimulated, stem, cell, 'differentiation,', a, response, likely, reflecting, gill, remodelling, in, response, to, its, altered, environment])]). relacion([sujeto(['This']), verbo([provides]), complemento([insight, to, the, role, of, zinc, during, cell, differentiation, and, illustrates, the, critical, nature, of, maintaining, zinc, status])]). relacion([sujeto(['The', inflammatory, cytokine, interleukin, '(', 'IL)-17', is]), verbo([involved]), complemento([in, the, pathogenesis, of, allergic, diseases])]). relacion([sujeto(['Here,', we]), verbo([report]), complemento([a, novel, subset, of, 'T(H)2', 'memory/effector', cells, that, coexpress, the, transcription, factors, 'GATA3', and, 'RORγt', and, coproduce, 'T(H)17', and, 'T(H)2', cytokines])]). relacion([sujeto(['The', number, of, 'IL-17-T(H)2', cells, was, significantly]), verbo([increased]), complemento([in, blood, of, patients, with, atopic, asthma])]). relacion([sujeto(['In', a, mouse, model, of, allergic, lung, 'diseases,', 'IL-17-producing', 'CD4(+)', 'T(H)2', cells, were]), verbo([induced]), complemento([in, the, inflamed, lung, and, persisted, as, the, dominant, 'IL-17-producing', 'T', cell, population, during, the, chronic, stage, of, asthma])]). relacion([sujeto(['Treating', cultured, bronchial, epithelial, cells, with, 'IL-17', plus, 'T(H)2', cytokines]), verbo([induced]), complemento([strong, 'up-regulation', of, chemokine, 'eotaxin-3,', 'Il8,', 'Mip1b,', and, 'Groa', gene, expression])]). relacion([sujeto(['Compared', with, classical, 'T(H)17', and, 'T(H)2', 'cells,', 'antigen-specific', 'IL-17-producing', 'T(H)2', cells]), verbo([induced]), complemento([a, profound, influx, of, heterogeneous, inflammatory, leukocytes, and, exacerbated, asthma])]). relacion([sujeto(['Our', findings, highlight, the, plasticity, of, 'T(H)2', memory, cells, and]), verbo([suggest]), complemento([that, 'IL-17-producing', 'T(H)2', cells, may, represent, the, key, pathogenic, 'T(H)2', cells, promoting, the, exacerbation, of, allergic, asthma])]). relacion([sujeto(['Although', 'NK', cells, in, the, mouse, are, thought, to, develop, in, the, bone, 'marrow,', a, small, population, of, 'NK', cells, in, the, thymus]), verbo([has]), complemento([been, shown, to, derive, from, a, 'GATA3-dependent', pathway])]). relacion([sujeto(['Characteristically,', thymic, 'NK', cells]), verbo([express]), complemento(['CD127', and, few, 'Ly49', molecules, and, lack, 'CD11b'])]). relacion([sujeto(['Because', these, 'NK', cells, develop, in, the, 'thymus,', the, question, of, their, relationship, to, the, 'T', cell, lineage]), verbo([has]), complemento([been, raised])]). relacion([sujeto(['Using', several, different, mouse, 'models,', we]), verbo([find]), complemento([that, unlike, 'T', 'cells,', thymic, 'NK', cells, are, not, the, progeny, of, 'Rorc-expressing', progenitors, and, do, not, express, 'Rag2', or, rearrange, the, 'TCRγ', locus])]). relacion([sujeto(['More', recent, studies, indicate, that, 'Bmp-antagonists', are, critical, for]), verbo([promoting]), complemento([preplacodal, development])]). relacion([sujeto(['We']), verbo([find]), complemento([that, preplacodal, development, occurs, in, two, phases, with, opposing, 'Bmp', requirements])]). relacion([sujeto(['Initially,', 'Bmp', is]), verbo([required]), complemento([before, gastrulation, to, 'co-induce', four, transcription, 'factors,', 'Tfap2a,', 'Tfap2c,', 'Foxi1,', and, 'Gata3,', which, establish, preplacodal, competence, throughout, the, nonneural, ectoderm])]). relacion([sujeto(['Subsequently,', 'Bmp', must, be, fully, blocked, in, late, gastrulation, by, dorsally]), verbo([expressed]), complemento(['Bmp-antagonists,', together, with, dorsally, expressed, 'Fgf', and, 'Pdgf,', to, specify, preplacodal, identity, within, competent, cells, abutting, the, neural, plate])]). relacion([sujeto(['Localized', ventral, misexpression, of, 'Fgf8', and, 'Chordin', can]), verbo([activate]), complemento([ectopic, preplacodal, development, anywhere, within, the, zone, of, 'competence,', whereas, dorsal, misexpression, of, one, or, more, competence, factors, can, activate, ectopic, preplacodal, development, in, the, neural, plate])]). relacion([sujeto(['Our', work, supports, a, relatively, simple, 'two-step', model, that, traces, regulation, of, preplacodal, development, to, late, blastula, 'stage,', resolves, two, distinct, phases, of, 'Bmp', 'dependence,', and, identifies, the, main, factors]), verbo([required]), complemento([for, preplacodal, competence, and, specification])]). relacion([sujeto(['The', classification, of, breast, cancer, into, multiple, molecular, subtypes]), verbo([has]), complemento([necessitated, the, need, for, biomarkers, that, can, assess, tumor, progression, and, the, effects, of, chemopreventive, agents, on, specific, breast, cancer, subtypes])]). relacion([sujeto(['FOXA1', is]), verbo([associated]), complemento([with, luminal, type, 'A', 'cancers,', while, 'GATA-3', is, a, marker, of, luminal, progenitor, cell, differentiation])]). relacion([sujeto(['In', both, control, and, 'PEITC-treated', 'groups,', there, was, a, progressive]), verbo([loss]), complemento([of, 'ERα', and, 'FOXA1', but, persistence, of, 'GATA-3', expression, indicating, that, the, tumors, retain, luminal, phenotype])]). relacion([sujeto(['Overall,', the, 'PyMT']), verbo([induced]), complemento([tumors, exhibited, the, entire, gamut, of, phenotypes, from, 'ERα+/FOXA1+/GATA-3+', tumors, in, the, early, stage, to, 'ERα±/FOXA1-/GATA-3+', in, the, late, stage])]). relacion([sujeto(['The', branchial, arch, enhancer, cooperates, with, the, somite, enhancer, region, to]), verbo([prevent]), complemento([an, inhibitory, activity, contained, in, the, first, intron])]). relacion([sujeto(['The', characterization, of, the, branchial, arch, enhancer]), verbo([has]), complemento([revealed, a, specific, role, of, the, transcription, factor, 'GATA3', in, the, regulation, of, 'N-myc', expression])]). relacion([sujeto(['TAL1', '(', also, known, as, 'SCL)', is]), verbo([expressed]), complemento([in, &, 'gt;40%', of, human, 'T', cell, acute, lymphoblastic, leukemias, '(', 'T-ALLs)'])]). relacion([sujeto(['TAL1', encodes, a, basic, 'helix-loop-helix', transcription, factor, that, can, interfere, with, the, transcriptional, activity, of, 'E2A', and, 'HEB', during, 'T', cell, 'leukemogenesis;', 'however,', the, oncogenic, pathways, directly]), verbo([activated]), complemento([by, 'TAL1', are, not, characterized])]). relacion([sujeto(['In', this, 'study,', we, show, 'that,', in, human, 'TAL1-expressing', 'T-ALL', cell, 'lines,', 'TAL1', directly]), verbo([activates]), complemento(['NKX3'])]). relacion([sujeto([1, ',', a, tumor, suppressor, gene]), verbo([required]), complemento([for, prostate, stem, cell, maintenance])]). relacion([sujeto([1, gene, activation, is]), verbo([mediated]), complemento([by, a, 'TAL1-LMO-Ldb1', complex, that, is, recruited, by, 'GATA-3', bound, to, an, 'NKX3'])]). relacion([sujeto([1, activation, is]), verbo([associated]), complemento([with, suppression, of, 'HP1-α', '(', heterochromatin, protein, 1, 'α)', binding, and, opening, of, chromatin, on, the, 'NKX3'])]). relacion([sujeto([1, is, necessary, for, 'T-ALL', 'proliferation,', can, partially, restore, proliferation, in, 'TAL1', knockdown, 'cells,', and, directly]), verbo([regulates]), complemento(['miR-17-92'])]). relacion([sujeto([1, gene, is]), verbo([expressed]), complemento([independently, of, the, 'Notch', 'pathway,', and, its, inactivation, impairs, proliferation])]). relacion([sujeto([1, knockdown, abrogates, the, ability, of, human, 'T-ALL', cells, to, efficiently]), verbo([induce]), complemento([leukemia, development, in, mice])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, tumor, suppressor, or, oncogenic, activity, of, 'NKX3'])]). relacion([sujeto(['Multiple', sclerosis, '(', 'MS)', is, hypothetically]), verbo([caused]), complemento([by, autoreactive, 'Th1', and, 'Th17', 'cells,', whereas, 'Th2', and, regulatory, 'T', cells, may, confer, protection])]). relacion([sujeto(['In', 'relapsing-remitting', 'MS,', diminished, expression, of, 'FOXP3', '(', 'Treg)', was]), verbo([found]), complemento(['(', p, &, 'lt;', 0.05, ')', ',', despite, normal, numbers, of, 'CD4(+)CD25(hi)Treg'])]). relacion([sujeto(['Immunoregulatory', 'EBI3', and, 'Th2-associated', 'GATA3', '(', '[', 'a-z]+)', was, also]), verbo([decreased]), complemento([in, 'MS', '(', p, &, 'lt;', 0.005, and, p, &, 'lt;', 0.05, ',', 'respectively)'])]). relacion([sujeto(['Analysis', of, transcription, factor, 'ratios,', comparing, 'TBX21/GATA3', and, 'RORC/FOXP3,', revealed, an]), verbo([increase]), complemento([in, the, 'RORC/FOXP3', ratio, in, patients, with, 'relapsing-remitting', 'MS', '(', p, &, 'lt;', 0.005, ')'])]). relacion([sujeto(['Our', findings, indicate, systemic, defects, at, the, mRNA, 'level,']), verbo([involving]), complemento([downregulation, of, beneficial, 'CD4(+)phenotypes'])]). relacion([sujeto(['A', large, number, of, hyposerotonergic, genetic, models]), verbo([have]), complemento([been, generated, over, the, past, few, years])]). relacion([sujeto(['Serotonin', '(', 5, -, 'HT)', depletion]), verbo([has]), complemento([been, obtained, via, targeting, of, genes, involved, in, 5, -, 'HT', synthesis, '(', 'Tph1', and, 'Tph2),', specification, and, determination, of, the, 5, -, 'HT', phenotype, during, development, '(', 'GATA3,', 'Pet1,', and, 'Lmx1b),', and, 5, -, 'HT', storage, or, clearance, '(', 'Vmat2', and, 'SERT)'])]). relacion([sujeto(['We', then, summarize, the, neurological, and, behavioral, alterations, that]), verbo([have]), complemento([been, observed, in, the, genetic, hyposerotonergic, models])]). relacion([sujeto(['Although', these, models, appear, to]), verbo([have]), complemento([normal, brain, development, and, do, not, exhibit, any, gross, morphological, 'defects,', problems, in, somatic, growth, and, physiological, functions, have, been, observed])]). relacion([sujeto(['Evidence', from, these, hyposerotonergic, models]), verbo([suggests]), complemento([that, the, developing, brain, may, not, need, 5, -, 'HT', for, the, establishment, of, general, organization, and, structure])]). relacion([sujeto(['The', transcription, factors, 'GATA3', and, 'ThPOK']), verbo([regulate]), complemento([lineage, commitment, of, conventional, 'MHC', class, 'II-restricted', 'CD4(+)', 'T', 'cells;', 'however,', their, role, in, 'CD4/CD8', expression, by, 'CD1d-restricted', 'NKT', cells, is, less, clear])]). relacion([sujeto(['This', study]), verbo([reveals]), complemento([that, 'GATA3', and, 'ThPOK', are, necessary, for, the, development, of, 'CD4(+)', 'NKT', cells])]). relacion([sujeto(['This', study, sheds, new, light, on, the, underlying, molecular, events]), verbo([leading]), complemento([to, the, emergence, of, distinct, 'NKT-cell', subsets])]). relacion([sujeto(['Among', other, pathogenetic, 'possibilities,', an, abnormal, reaction, to, a, luminal, antigen]), verbo([has]), complemento([been, discussed])]). relacion([sujeto(['In', 'LC,', 10, -, 20, '%', of, intraepithelial, lymphocytes, '(', 'IEL)']), verbo([expressed]), complemento(['GATA-3', and, the, remaining, 'T-bet,', whereas, in, 'CD,', all, 'IEL', were, 'T-bet-positive'])]). relacion([sujeto(['The', majority, of, the, 'CD4+', 'T', cells, were, 'GATA-3+,', while, 'T-bet', and, 'GATA-3', were]), verbo([expressed]), complemento([at, a, similar, frequency, by, the, 'CD8+', 'T', cells])]). relacion([sujeto(['Allergic', airway, inflammation, is, a, disease, in, which, 'T', helper, 2, '(', 'Th2)', cells]), verbo([have]), complemento([a, critical, function])]). relacion([sujeto(['Recently,', a, network, of, 'PB1-containing', adapters, and, kinases]), verbo([has]), complemento([been, shown, to, be, essential, in, this, process, owing, to, its, function, in, regulating, cell, polarity, and, the, activation, of, critical, transcription, factors])]). relacion([sujeto(['Here,', we, show, in, vivo, data, showing, that, 'T-cell-specific', 'NBR1-deficient', mice, show, impaired, lung, inflammation, and]), verbo([have]), complemento([defective, 'Th2', differentiation, ex, vivo, with, alterations, in, 'T-cell', polarity, and, the, selective, inhibition, of, 'Gata3', and, nuclear, factor, of, activated, 'T', c1, activation])]). relacion([sujeto(['In', 'Shn-2-deficient', 'mice,', the, activation, of, 'NF-kappaB', in, 'CD4', 'T', cells, is, upregulated, and, their, ability, to, differentiate, into, 'Th2', cells, is]), verbo([enhanced]), complemento([in, part, through, the, increased, expression, of, 'GATA3'])]). relacion([sujeto(['Shn-2', is]), verbo([found]), complemento([to, compete, with, p50, 'NF-kappaB', for, binding, to, a, consensus, 'NF-kappaB', motif, and, inhibit, the, 'NF-kappaB-driven', promoter, activity])]). relacion([sujeto(['In', 'addition,', 'Th2-driven', allergic, airway, inflammation, was]), verbo([enhanced]), complemento([in, 'Shn-2-deficient', mice])]). relacion([sujeto(['The', expression, levels, of, 'CD69', and, the, number, ofapoptotic, cells, are, selectively]), verbo([increased]), complemento([in, 'Shn-2-deficient', 'Thl/Th2', cells, when, they, are, transferred, into, syngeneic, host, 'animals,', in, which, memoryh, 'Th1/Th2', cells, are, generated, within, a, month])]). relacion([sujeto(['In', 'addition,', an]), verbo([increased]), complemento([susceptibility, to, apoptotic, cell, death, is, also, observed, in, vitro, accompanied, with, the, increased, expression, of, 'FasL,', one, of, the, 'NF-kappaB-dependent', genes])]). relacion([sujeto(['Th2', effector, cells, overexpressing, the, p65, subunit, of, 'NF-kappaB', demonstrate, a]), verbo([decreased]), complemento([cell, survival, particularly, in, the, lymph, node])]). relacion([sujeto(['These', results, indicate, that, 'Shn-2-mediated', repression, of, 'NF-kappaB', is]), verbo([required]), complemento([for, cell, survival, and, the, successful, generation, of, memory, 'Th1/Th2', cells])]). relacion([sujeto(['This', may, point, to, the, possibility, that, after, antigen, clearance, the, recovery, of, the, quiescent, state, in, effector, 'Th', cells, is]), verbo([required]), complemento([for, the, generation, of, memory, 'Th', cells])]). relacion([sujeto(['The', lmo2, gene, is, a, specific, oncogene, in, 'T-cell', 'leukemia,', for, its, ectopic, expression]), verbo([causes]), complemento([both, increased, 'pro-T-cell', proliferation, and, differentiation, 'arrest,', leading, to, the, onset, of, leukemia])]). relacion([sujeto(['Notably,', 'DeltaEF1', '(', also, known, as, 'ZEB1),', a, member, of, zinc, 'finger-homeodomain', family, transcription, 'factor,', also, exhibits, crucial, function, in]), verbo([promoting]), complemento(['T-cell', differentiation])]). relacion([sujeto(['In', this, 'study,', we]), verbo([found]), complemento([that, 'DeltaEF1', was, positively, regulated, by, 'T-lineage-specific', transcriptional, regulator, 'GATA3,', while, ectopically, expressed, 'LMO2', targeted, to, 'DeltaEF1', promoter, by, interaction, with, 'GATA3', and, inhibited, 'DeltaEF1', expression, in, transcriptional, level])]). relacion([sujeto(['Moreover,', 'LMO2']), verbo([interacted]), complemento([with, the, 'N-terminal', zinc, finger, domain, of, 'DeltaEF1', protein, and, inhibited, its, positive, transcriptional, regulatory, function, by, this, interaction])]). relacion([sujeto(['Taken', 'together,', our, findings, revealed, that, ectopically]), verbo([expressed]), complemento(['LMO2', impaired, the, function, of, 'DeltaEF1', in, both, transcriptional, and, protein, levels, and, identified, 'DeltaEF1', as, a, novel, pathogenic, target, of, 'LMO2', in, 'T-cell', leukemia])]). relacion([sujeto(['Blood', eosinophilia, correlates, with, disease, 'activity,', and]), verbo([activated]), complemento(['T', cells, from, 'CSS', patients, are, predominantly, 'T', helper, 2, '(', 'Th2)'])]). relacion([sujeto(['Interleukin', '(', 'IL)-25']), verbo([has]), complemento([been, shown, to, link, innate, and, adaptive, immunity, by, enhancing, 'Th2', cytokine, production])]). relacion([sujeto(['We']), verbo([found]), complemento([increased, levels, of, 'IL-25', in, the, serum, of, active, 'CSS', patients, '(', 952, ±, 697, vs, 75, ±, 49, 'pg/mL', in, inactive, patients, and, 47, ±, 6, 'pg/mL', in, healthy, 'donors)'])]). relacion([sujeto(['Eosinophils', were, the, main, source, of, 'IL-25,', whereas]), verbo([activated]), complemento(['CD4(+)', memory, 'T', cells, were, the, 'IL-17RB-expressing', cells, in, 'CSS'])]). relacion([sujeto(['IL-25']), verbo([enhanced]), complemento([the, production, of, 'IL-4,', 'IL-5,', and, 'IL-13', by, activated, peripheral, blood, mononuclear, cells])]). relacion([sujeto(['Our', findings]), verbo([suggest]), complemento([that, 'eosinophils,', through, the, production, of, 'IL-25,', exert, a, critical, role, in, promoting, 'Th2', responses, in, target, tissues, of, 'CSS'])]). relacion([sujeto(['High', rates, of, 'embryonic,', 'fetal,', or, placental, abnormalities]), verbo([have]), complemento([consistently, been, observed, in, bovine, cloning])]). relacion([sujeto(['In', mouse, 'embryos,', differentiation, of, 'ICM', and, 'TE', is]), verbo([regulated]), complemento([by, various, transcription, 'factors,', such, as, 'OCT-4,', 'CDX2,', and, 'TEAD4,', but, molecular, mechanisms, that, regulate, differentiation, in, bovine, embryos, remain, unknown])]). relacion([sujeto(['To', clarify, gene, transcripts]), verbo([involved]), complemento([in, segregation, of, 'ICM', and, 'TE', lineages, in, bovine, 'embryos,', we, examined, the, relative, abundances, of, 'OCT-4,', 'CDX2,', 'TEAD4,', 'GATA3,', 'NANOG,', and, 'FGF4', transcripts, in, blastocyst, embryos, derived, from, in, vitro, fertilization, '(', 'IVF)'])]). relacion([sujeto(['Furthermore,', transcript, levels, of, such, genes, in, bovine, embryos, derived, from, somatic, cell]), verbo([nuclear]), complemento([transfer, '(', 'NT-SC)', and, in, vivo, '(', 'Vivo)', were, also, compared])]). relacion([sujeto(['We', observed, aberrant, expression, patterns, of, various, genes]), verbo([involved]), complemento([in, segregation, of, 'ICM', and, 'TE', lineages, in, bovine, 'NT-SC', embryos])]). relacion([sujeto(['These', results, raise, the, possibility, that, abnormalities, in, the, cloned, fetus, and, placenta, are, related, to, the, aberrant, expression, of, genes]), verbo([involved]), complemento([in, segregation, and, differentiation, process, in, the, early, developmental, stage])]). relacion([sujeto(['Childhood', acute, lymphoblastic, leukemia, '(', 'ALL)']), verbo([has]), complemento([been, hypothesized, to, have, an, 'infection-', and, 'immune-related', etiology])]). relacion([sujeto(['The', lack, of, immune, priming, in, early, childhood, may, result, in, abnormal, immune, responses, to, infections, later, in, life, and]), verbo([increase]), complemento(['ALL', risk])]). relacion([sujeto(['This']), verbo([increased]), complemento([risk, was, stronger, among, firstborn, children, of, all, ethnicities, and, among, 'non-Hispanic', children, with, less, day, care, 'attendance,', consistent, with, the, hypothesis, about, the, role, of, early, immune, modulation, in, the, development, of, childhood, 'ALL'])]). relacion([sujeto(['Haplotype', analyses, identified, additional, regions, of, 'CD28,', 'FCGR2,', 'GATA3,', 'IL2RA,', 'STAT4,', and, 'STAT6']), verbo([associated]), complemento([with, childhood, 'ALL'])]). relacion([sujeto(['Polymorphisms', of, genes, on, the, adaptive, immunity, pathway, are]), verbo([associated]), complemento([with, childhood, 'ALL', risk])]). relacion([sujeto(['Further', confirmation, is]), verbo([required]), complemento([to, detect, functional, variants, in, the, significant, genomic, regions, identified, in, this, 'study,', in, particular, for, 'IL12A'])]). relacion([sujeto(['We', previously, showed, that, the, sequential, activity, of, two, zinc, finger, transcription, 'factors,', 'Gata3', and, 'Thpok,']), verbo([promotes]), complemento([the, differentiation, of, 'conventional,', 'MHC', 'II-restricted', thymocytes, into, 'CD4(+)', 'T', cells])]). relacion([sujeto(['In', the, current, 'study,', we, show, that, a, 'Gata3-Thpok', cascade, is]), verbo([required]), complemento([for, the, differentiation, of, 'CD4(+)', iNKT, cells])]). relacion([sujeto(['Gata3', is]), verbo([required]), complemento([for, iNKT, cells, to, express, 'Thpok,', whereas, 'Thpok', is, needed, for, proper, 'NKT', cell, 'differentiation,', and, notably, for, 'NKT', cells, to, maintain, 'CD4', and, terminate, 'CD8', expression])]). relacion([sujeto(['GATA', transcription, factors]), verbo([have]), complemento([been, implicated, in, controlling, adipogenesis, in, 'Drosophila', and, in, mammals])]). relacion([sujeto(['In', 'mammals,', both, 'GATA2', and, 'GATA3']), verbo([have]), complemento([been, shown, to, be, present, in, 'preadipocytes,', and, their, silencing, allows, the, onset, of, adipogenesis])]). relacion([sujeto(['GATA', factors]), verbo([have]), complemento([been, found, to, operate, through, recruiting, cofactors, of, the, 'Friend', of, 'GATA', '(', 'FOG)', family])]). relacion([sujeto(['FOG', 'proteins,', in, 'turn,']), verbo([recruit]), complemento(['co-regulators,', including, 'C-terminal', binding, proteins, '(', 'CTBPs)'])]). relacion([sujeto(['We']), verbo([have]), complemento([investigated, whether, 'FOGs', and, 'CTBPs', influence, adipogenesis])]). relacion([sujeto(['We']), verbo([found]), complemento([that, both, 'FOG1', and, 'FOG2', are, expressed, in, cells, prior, to, adipogenesis, but, are, 'down-regulated', as, adipogenesis, proceeds])]). relacion([sujeto(['Mutant', versions, of, 'FOG2', unable, to]), verbo([bind]), complemento(['CTBP', or, 'GATA', proteins, are, impaired, in, their, inability, to, inhibit, adipogenesis])]). relacion([sujeto(['Finally,', a, mutant, version, of, 'GATA2,', unable, to]), verbo([associate]), complemento([with, 'FOGs,', also, displays, abnormal, activity, and, causes, enhanced, cell, proliferation])]). relacion([sujeto(['As', 'Gata3', expression, is]), verbo([maintained]), complemento([up, to, the, adult, 'stage,', we, addressed, its, function, in, differentiated, sympathoadrenal, cells, at, embryonic, and, adult, stages, by, conditional, 'Gata3', elimination])]). relacion([sujeto(['Interestingly,', 'Gata3', elimination, in, 'DBH-expressing', neurons, of, adult, animals, also, results, in, a, virtually, complete]), verbo([loss]), complemento([of, sympathetic, neurons])]). relacion([sujeto(['These', results, demonstrate, that, 'Gata3', is, continuously]), verbo([required]), complemento([for, maintaining, survival, but, not, differentiation, in, the, sympathetic, neuron, lineage, up, to, mature, neurons, of, adult, animals])]). relacion([sujeto(['We', show, in, this, study, that, 'IL-4', stimulation]), verbo([induces]), complemento(['GATA-3', mRNA, 'upregulation,', but, the, level, of, 'GATA-3', protein, induced, is, insufficient, for, 'Th2', differentiation])]). relacion([sujeto(['The', levels, of, 'GATA-3', protein, and, 'Th2', differentiation, are]), verbo([enhanced]), complemento([by, concomitant, 'TCR', signaling, through, the, 'PI3K/mammalian', target, of, rapamycin, pathway])]). relacion([sujeto(['The', 'PI3K-mediated']), verbo([increase]), complemento([in, 'GATA-3', protein, occurs, without, increasing, the, 'GATA-3', mRNA, level])]). relacion([sujeto(['Rather,', 'TCR', signaling, through, 'PI3K', specifically]), verbo([enhances]), complemento([the, translation, rate, of, 'GATA-3', without, affecting, the, protein, stability])]). relacion([sujeto(['As', compared, with, 'Group', 'A,', the, airway, 'hyper-reactivity,', airway, 'inflammation,', cell, count, and, eosinophil, percentage, in, 'BALF,', levels, of, total, serum, 'IgE', and, 'BALF', 'IL-4', and, 'IL-13,', and, 'GATA-3', protein, expression, in, the, lung, tissue, were, significantly]), verbo([increased]), complemento([in, 'Group', 'B', '(', 'P', &, 'lt;', 0.05, ')'])]). relacion([sujeto(['Belatacept', is, thought, to, disrupt, the, interaction, between, 'CD80/86', and, 'CD28,', thus]), verbo([preventing]), complemento(['T-cell', activation, by, blocking, the, 'co-stimulatory', second, signal])]). relacion([sujeto(['However,', the, consequences, on, the, 'T-cell', profile, in, human, renal, transplant, cases]), verbo([have]), complemento([not, been, determined])]). relacion([sujeto(['These', results, are, in, agreement, with, in, vitro, data]), verbo([suggesting]), complemento([that, 'CD28', is, a, major, 'co-stimulatory', signal, of, both, 'Tregs', development, and, peripheral, homeostasis, but, contrast, with, clinical, trials, showing, a, better, 1, -, year, graft, function, and, a, lower, incidence, of, chronic, allograft, nephropathy, in, patients, receiving, 'Belatacept', than, patients, treated, with, 'CNI'])]). relacion([sujeto(['They']), verbo([suggest]), complemento([that, immune, benefits, induced, by, 'Belatacept', are, not, mediated, by, 'Treg', expansion, and, that, 'FOXP3', is, not, by, itself, a, prognostic, marker, of, 'long-term', graft, function, in, a, 'non-inflammatory', context])]). relacion([sujeto(['These', results]), verbo([have]), complemento([to, 'be,', 'however,', considered, as, preliminary, since, the, size, of, our, study, population, is, limited])]). relacion([sujeto(['The', transcription, factor, network, in, 'Hodgkin', lymphoma, '(', 'HL)', represents, a, unique, composition, of, proteins]), verbo([found]), complemento([in, no, other, hematopoietic, cell])]). relacion([sujeto(['We', demonstrate]), verbo([binding]), complemento([of, 'NFκB', and, 'Notch-1,', 2, factors, with, deregulated, activity, in, 'HL', to, 'GATA3', promoter, elements])]). relacion([sujeto(['Interference', with, 'NFκB', and, 'Notch-1', activity]), verbo([led]), complemento([to, decreased, 'GATA3', 'expression,', indicating, a, dependency, of, deregulated, 'GATA3', expression, on, these, transcription, factors])]). relacion([sujeto(['Conclusively,', aberrant, 'GATA3', expression, in, 'HRS', cells, is]), verbo([stimulated]), complemento([by, the, deregulated, constitutive, activity, of, 'NFκB', and, 'Notch-1,', indicating, a, complex, network, of, deregulated, transcription, factors, in, these, cells])]). relacion([sujeto(['The', clinical, impact, of, 'FLT3-internal', tandem, duplications, '(', 'ITDs),', an, adverse, prognostic, marker, in, adults, aged, &, 'lt;', 60, years, with, primary, cytogenetically, normal, acute, myeloid, leukemia, '(', 'CN-AML),']), verbo([requires]), complemento([further, investigation, in, older, patients])]). relacion([sujeto(['In', 'CN-AML', patients, aged, '≥', 60, years, treated, on, 'Cancer', and, 'Leukemia', 'Group', 'B', frontline, 'trials,', we]), verbo([found]), complemento([that, 'FLT3-ITD', remained, associated, with, shorter, 'disease-free', survival, '(', 'P', &, 'lt;'])]). relacion([sujeto(['FLT3-ITD', identifies, older, 'CN-AML', patients, with, molecular, high, risk, and, is]), verbo([associated]), complemento([with, 'gene-', and, 'microRNA-expression', signatures, that, provide, biologic, insights, for, novel, therapeutic, approaches])]). relacion([sujeto(['The', generation, of, specific, 'T', lymphocyte, subsets, is, under, the, strict, control, of, specific, transcription, 'factors,', as, this]), verbo([has]), complemento([been, shown, by, knockout, experiments, in, mice])]). relacion([sujeto(['Here,', we, show, that, siRNAs, that, specifically]), verbo([target]), complemento([the, transcription, factor, 'Gata3', '(', which, is, required, for, the, development, of, 'T', helper, 1, 'cells)', or, 'T-Bet', '(', which, is, required, for, the, development, of, 'T', helper, 2, 'cells)', can, be, effective, in, vivo])]). relacion([sujeto(['Thus,', the, intraperitoneal, injection, of, siRNAs, specific, for, 'Gata3', or, 't-Bet']), verbo([leads]), complemento([to, the, specific, depletion, of, their, target, gene, products, in, 'vivo,', in, the, spleen, and, in, the, lymph, nodes, of, mice])]). relacion([sujeto(['In', this, 'setting,', the, siRNA]), verbo([targeting]), complemento(['t-Bet', was, able, to, accelerate, tumor, growth, while, the, siRNA, targeting, 'Gata3', significantly, reduced, the, proliferation, of, cancer, cells, in, vivo])]). relacion([sujeto(['These', effects, were, dependent, on, the, immune, response, elicited, by, dying, tumor, cells, because, both, siRNAs, failed, to]), verbo([modulate]), complemento([the, growth, of, tumors, in, 'non-vaccinated', mice])]). relacion([sujeto(['Moreover,', discontinuation, of, 'CNIs\'', treatment, allows, 'FOXP3+', regulatory, 'T-cells', 'development,', resulting, in, a, significant]), verbo([decrease]), complemento([of, 'anti-donor', immune, reactivity])]). relacion([sujeto(['We', demonstrated, previously, that, 'GATA-3', overexpression, markedly]), verbo([enhanced]), complemento(['allergen-induced', airway, inflammation, and, airway, 'remodelling,', including, subepithelial, 'fibrosis,', and, smooth, muscle, cell, 'hyperplasia,', in, transgenic, mice])]). relacion([sujeto(['Because', cysteinyl, leukotrienes, '(', 'cysLTs)']), verbo([have]), complemento([been, shown, to, be, involved, in, such, structural, 'changes,', the, effects, of, a, specific, cysLT1, receptor, 'antagonist,', 'montelukast,', were, evaluated, in, a, mouse, model, of, chronic, asthma])]). relacion([sujeto(['CysLTs', in, the, lung, were]), verbo([increased]), complemento([after, repeated, allergen, 'challenges,', and, significantly, enhanced, in, 'GATA-3-overexpressing', mice])]). relacion([sujeto(['The']), verbo([enhanced]), complemento([cysLT, levels, were, accompanied, by, the, development, of, 'eosinophilia,', smooth, muscle, cell, 'hyperplasia,', and, increased, stromal, 'cell-derived', 'factor-1', gene, expression, with, a, small, increase, in, 'pro-collagen', gene, expression, in, 'OVA-challenged', 'GATA-3-overexpressing', 'mice,', but, not, in, 'wild-type', mice])]). relacion([sujeto(['Montelukast', significantly]), verbo([decreased]), complemento([lung, cysLT, levels, and, inhibited, the, 'GATA-3-overexpression-related', airway, 'remodelling,', potently, preventing, smooth, muscle, cell, 'hyperplasia,', but, partially, suppressed, the, increased, 'pro-collagen', gene, expression, and, eosinophilic, inflammation])]). relacion([sujeto(['Increases', in, the, levels, of, 'IL-4,', 'IL-5,', 'IL-13,', and, eotaxin, in, bronchial, lavage, and, 'TGF-β', gene, expression, in, the, lungs, were]), verbo([induced]), complemento([by, 'OVA', in, both, mouse, genotypes])]). relacion([sujeto(['Montelukast', efficaciously]), verbo([prevented]), complemento([airway, inflammation, and, remodelling, in, a, 'GATA-3-overexpression', antigen, challenge, mouse, model, by, decreasing, the, 'cysLT-driven', 'Th2', cytokine, cycle, of, amplification, of, airway, pathologies])]). relacion([sujeto(['GATA-binding', 'protein-3', '(', 'GATA-3)']), verbo([regulates]), complemento([the, 'T', helper, type, 2, '(', 'Th2)', cytokine, locus, through, induction, of, chromatin, remodelling])]). relacion([sujeto(['To', understand, this, mechanism, 'better,', we, screened, 'GATA-3']), verbo([interacting]), complemento([proteins, using, affinity, purification, and, mass, spectrometry])]). relacion([sujeto(['We']), verbo([found]), complemento([that, 'GATA-3', bound, to, 'metastasis-associated', protein, 2, '(', 'MTA-2),', a, component, of, the, 'NuRD', chromatin, remodelling, complex])]). relacion([sujeto(['GATA-3', and, 'MTA-2', in, turn]), verbo([bound]), complemento([to, several, regulatory, regions, of, the, 'Th2', cytokine, locus, and, the, ifng, promoter])]). relacion([sujeto(['Cell', transfection, assay, showed, that, 'MTA-2']), verbo([acted]), complemento([as, an, antagonist, with, 'GATA-3', in, the, expression, of, 'Th2', 'cytokines,', but, 'co-operated', with, 'GATA-3', in, the, repression, of, the, ifng, gene, expression])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, 'GATA-3', interacts, with, 'MTA-2', to, 'co-ordinately', regulate, 'Th2', cytokine, and, ifng, loci, during, 'T', helper, cell, differentiation])]). relacion([sujeto(['We']), verbo([report]), complemento([here, the, cloning, of, rainbow, trout, 'Oncorhynchus', mykiss, 'T-bet', and, 'GATA3,', to, allow, the, future, evaluation, of, the, existence, of, 'Th1', and, 'Th2', cells, in, salmonid, fish])]). relacion([sujeto(['The', trout, 'T-bet', translation, shares, high, amino, acid, identities, to, other, fish, 'T-bet', molecules, '(', 71, -, 72, '%', ')', but, low, identities, to, mammalian, 'T-bet', genes, '(', 41, -, 42, '%', ')', ',', although, the, middle, 'T-box', 'DNA']), verbo([binding]), complemento([domain, is, highly, conserved, among, all, the, 'T-bet', proteins, from, fish, and, mammals])]). relacion([sujeto(['The', trout, 'GATA3']), verbo([has]), complemento([high, amino, acid, sequence, identities, '(', 73, -, 88, '%', ')', to, all, known, vertebrate, 'molecules,', with, two, highly, conserved, zinc, finger, motifs])]). relacion([sujeto(['T-bet', and, 'GATA3', expression, was]), verbo([modulated]), complemento([by, different, stimulants])]). relacion([sujeto(['The', 'T', cell, stimulant, 'PHA', 'up-regulated', the, expression, of, both, 'T-bet', and, 'GATA3', in, 'splenocytes,']), verbo([suggesting]), complemento([that, they, may, be, mainly, expressed, by, activated, 'T', cells])]). relacion([sujeto(['The', expression, of, 'T-bet', and, 'GATA3', in, the, spleen, was]), verbo([increased]), complemento([by, acute, 'stress,', but, their, expression, was, inhibited, by, bacterial, '(', 'Yersinia', 'ruckeri)', infection])]). relacion([sujeto(['In', a, parasitic, infection, 'model,', 'Tetracapsuloides', bryosalmonae, infection]), verbo([induced]), complemento([a, biased, gene, expression, profile, where, a, large, increase, in, the, expression, of, 'T-bet,', 'IFN-gamma', and, 'IL-2', was, 'seen,', suggesting, that, a, 'Th1-like', response, is, likely, induced, by, this, disease])]). relacion([sujeto(['A', better, understanding, of, pathogen]), verbo([modulated]), complemento([expression, of, 'T-bet', and, 'GATA3,', and, the, potential, underlying, host, immune, responses, elicited, as, a, consequence, of, their, 'expression,', may, allow, novel, future, control, measures, against, disease, in, fish, to, be, developed])]). relacion([sujeto(['The', levels, of, 'IL-18', and, 'IL-18Ralpha', were]), verbo([increased]), complemento([in, active, 'ITP', patients, as, compared, with, those, in, the, controls, '(', 'P', &, 'lt;', 0.05, ')'])]). relacion([sujeto(['The', levels, of, 'IL-18', mRNA, '(', 0.12, +, or, -, 0.02, ')', and, 'T-bet', mRNA, '(', 0.07, +, or, -, 0.02, ')', were, significantly]), verbo([increased]), complemento([in, patients, with, active, 'ITP', as, compared, with, those, in, the, controls, '(', 'P', &, 'lt;', 0.05, ')', ',', while, 'GATA-3', mRNA, '(', 0.0039, +, or, -, 0.0014, ')', were, significantly, decreased, in, patients, with, active, 'ITP', '(', 'P', &, 'lt;', 0.05, ')'])]). relacion([sujeto(['It', is, also]), verbo([suggested]), complemento([that, 'IL-18', has, potential, association, with, the, development, of, 'ITP'])]). relacion([sujeto(['Especially,', it, may]), verbo([provide]), complemento([a, new, treatment, method, for, 'ITP', by, regulating, the, ratio, of, 'T-bet', and, 'GATA-3', and, resuming, the, balance, of, 'Th1/Th2'])]). relacion([sujeto(['Many', functions, of, the, mammalian]), verbo([target]), complemento([of, rapamycin, '(', 'mTOR)', complex, 1, '(', 'mTORC1)', have, been, 'defined,', but, relatively, little, is, known, about, the, biology, of, an, alternative, mTOR, 'complex,', mTORC2])]). relacion([sujeto([mTORC2]), verbo([promoted]), complemento([phosphorylation, of, protein, kinase, 'B', '(', 'PKB,', or, 'Akt)', and, 'PKC,', 'Akt', 'activity,', and, nuclear, 'NF-kappaB', transcription, factors, in, response, to, 'T', cell, activation])]). relacion([sujeto(['Complementation', with, active, 'Akt', restored, only, 'T-bet', transcription, factor, expression, and, 'Th1', cell, 'differentiation,', whereas]), verbo([activated]), complemento(['PKC-theta', reverted, only, 'GATA3', transcription, factor, and, the, 'Th2', cell, defect, of, mTORC2, mutant, cells])]). relacion([sujeto(['Collectively,', the, data, uncover, vital, 'mTOR-PKC', and, 'mTOR-Akt', connections, in, 'T', cell, differentiation, and]), verbo([reveal]), complemento([distinct, pathways, by, which, mTORC2, regulates, development, of, 'Th1', and, 'Th2', cell, subsets])]). relacion([sujeto(['This', factor]), verbo([acts]), complemento([in, concert, with, 'Nkx2'])]). relacion([sujeto(['These', factors, are, also]), verbo([required]), complemento([for, the, expression, of, the, 'zinc-finger', transcription, factor, 'Gata2', in, the, lateral, floor, plate])]). relacion([sujeto(['In', 'turn,', 'Gata2', is, necessary, for, expression, of, the, basic, 'helix-loop-helix', transcription, factor, 'Tal2', that]), verbo([acts]), complemento([upstream, of, the, 'GABA-synthesizing', enzyme, glutamic, acid, decarboxylase, 67, gene, '(', 'gad67)', in, 'KA\'', cells])]). relacion([sujeto(['The', functional, connections, between, the, different, regulatory, 'genes,', 'however,', differ, in, the, two, 'GABAergic', cell, 'types:', although, gata2, and, tal2, are]), verbo([expressed]), complemento([in, 'KA\'', 'cells,', they, are, dispensable, for, gad67, expression, in, these, cells])]). relacion([sujeto(['Instead,', olig2, and, gata3, are]), verbo([required]), complemento([for, the, differentiation, of, 'gad67-expressing', 'KA\'', cells])]). relacion([sujeto(['This']), verbo([suggests]), complemento([that, the, layout, of, regulatory, networks, is, crucially, dependent, on, the, lineage, that, differs, between, 'KA\'', and, 'KA\'', cells])]). relacion([sujeto(['To', discern, the, interrelationship, of, 'T', cell, differentiation, and, outcome, of, human, 'infection,', we, examined, factors, that]), verbo([regulate]), complemento(['T', cell, differentiation, and, 'Th1/Th2', cytokine, responses, in, asymptomatic, 'infection,', active, and, historical, chronic, and, recurrent, cutaneous, leishmaniasis])]). relacion([sujeto(['Down-regulation', of, 'T-bet', and, 'GATA-3', expression, and]), verbo([increased]), complemento([interleukin, 2, 'secretion,', compared, with, control, 'subjects,', was, directly, correlated, with, 'Foxp3', expression, and, interleukin, 13, secretion, in, chronic, disease])]). relacion([sujeto(['Sorted', 'CD4(+)', 'T', cells, obtained, from, the, splenocytes, of, 'BALB/c', mice, were]), verbo([activated]), complemento([with, 'anti-CD3/anti-CD28', and, then, cultured, in, medium, that, contained, 'CR', medium, under, 'Th1', inducing, or, 'Th2', inducing, conditions])]). relacion([sujeto(['CR', had, no, mitogenic, effects, on, 'un-stimulated', 'CD4(+)', 'T', 'cells,', 'however,', it]), verbo([increased]), complemento([the, 'CD4(+)', 'T', cell, population])]). relacion([sujeto(['Th1/Th2', polarization, experiments, revealed, that, 'CR']), verbo([enhanced]), complemento(['IFN-gamma', secretion, in, 'Th1', 'cells,', but, reduced, the, 'IL-4', in, 'Th2', 'cells,', and, this, occurred, in, a, 'dose-dependent', manner, and, showed, significances])]). relacion([sujeto(['In', 'addition,', under, 'Th1/Th2', skewed, 'conditions,', the, transcription, levels, of, 'IFN-gamma', and, 'T-bet', were, considerably, 'increased,', while, the, expressions, of, 'IL-4', and, 'GATA-3', were, relatively]), verbo([decreased]), complemento([with, 'CR', treatment])]). relacion([sujeto(['These', findings]), verbo([suggest]), complemento([that, 'CR', enhances, 'Th1', lineage, development, by, increasing, 'Th1', specific, cytokine, expression, and, secretion, and, reduces, 'Th2', lineage, development, by, repressing, 'Th2', specific, cytokine, productions])]). relacion([sujeto(['Therefore,', 'CR', extract, may, be, useful, for]), verbo([preventing]), complemento([the, onset, of, allergies, or, improving, allergic, symptoms])]). relacion([sujeto(['This']), verbo([suggests]), complemento([a, role, for, 'WASp', in, patterning, 'T(H)', subtype, 'immunity,', yet, the, molecular, basis, for, the, 'TH1-TH2', imbalance, in, human, 'WAS', is, unknown])]). relacion([sujeto(['We']), verbo([have]), complemento([discovered, a, nuclear, role, for, 'WASp', in, the, transcriptional, regulation, of, the, 'TH1', regulator, gene, 'TBX21', at, the, chromatin, level])]). relacion([sujeto(['In', primary, 'TH1-differentiating', 'cells,', a, fraction, of, 'WASp', is]), verbo([found]), complemento([in, the, 'nucleus,', where, it, is, recruited, to, the, proximal, promoter, locus, of, the, 'TBX21', 'gene,', but, not, to, the, core, promoter, of, 'GATA3', '(', a, 'TH2', regulator, 'gene)', or, 'RORc', '(', a, 'TH17', regulator, 'gene)'])]). relacion([sujeto(['Functionally,']), verbo([nuclear]), complemento(['WASp', associates, with, 'H3K4', trimethyltransferase, '[', 'RBBP5', '(', 'retinoblastoma-binding', protein, 5, ')', ']', and, 'H3K9/H3K36', tridemethylase, '[', 'JMJD2A', '(', 'Jumonji', 'domain-containing', protein, 2, 'A)]', 'proteins,', and, their, enzymatic, activity, in, vitro, and, in, vivo, is, required, for, achieving, 'transcription-permissive', chromatin, dynamics, at, the, 'TBX21', proximal, promoter, in, primary, differentiating, 'TH1', cells])]). relacion([sujeto(['During', 'TH1', 'differentiation,', the]), verbo([loss]), complemento([of, 'WASp', accompanies, decreased, enrichment, of, 'RBBP5', 'and,', in, a, subset, of, 'WAS', 'patients,', also, of, filamentous, actin, at, the, 'TBX21', proximal, promoter, locus])]). relacion([sujeto(['Our', findings]), verbo([reveal]), complemento([a, previously, unappreciated, role, of, 'WASp', in, the, epigenetic, control, of, 'T-BET', transcription, and, provide, a, new, mechanism, for, the, pathogenesis, of, 'WAS', by, linking, aberrant, histone, methylation, at, the, 'TBX21', promoter, to, dysregulated, adaptive, immunity])]). relacion([sujeto(['Activation', of, naive, 'CD8', 'T', cells, in, vitro, in, the, presence, of, 'IL-4']), verbo([induces]), complemento([type, 2, cytokine, 'expression,', loss, of, 'CD8', 'expression,', and, reduced, cytolytic, potential])]). relacion([sujeto(['It']), verbo([has]), complemento([not, been, 'established,', 'however,', whether, 'IL-4', can, induce, comprehensive, type, 2, cytokine, expression, by, 'CD8', 'T', cells, in, 'vivo,', nor, whether, the, effects, of, 'IL-4', on, type, 2, cytokine, production, by, 'CD8', 'T', cells, can, be, inhibited, by, 'IFN-gamma'])]). relacion([sujeto(['Furthermore,', disparate, results]), verbo([have]), complemento([been, reported, regarding, the, 'anti-tumor', ability, of, type, 2, polarized, effector, 'CD8', 'T', 'cells,', and, the, effects, of, 'IFN-gamma', in, this, respect, remain, unknown])]). relacion([sujeto(['To', address, these, 'questions,', 'wild-type', or, 'IFN-gamma-deficient', 'OVA-specific', 'CD8(+)', 'T', cells, were]), verbo([activated]), complemento([in, 'RAG-2(-/-)', gamma, 'c(-/-)', recipients, with, control, or, 'IL-4-expressing', 'OVA(+)', tumor, 'cells,', and, then, transferred, to, secondary, recipients, for, tumor, challenge])]). relacion([sujeto(['Tumor-derived', 'IL-4']), verbo([induced]), complemento([the, expression, of, type, 2, cytokines, and, the, transcription, factor, 'GATA-3', by, responding, 'CD8', 'T', cells, while, reducing, their, 'CD8', coreceptor, expression, and, ability, to, eliminate, a, secondary, tumor, challenge])]). relacion([sujeto(['These', findings, may, explain, the, anomalies, in, the]), verbo([reported]), complemento([functional, phenotype, of, type, 2, polarized, 'CD8', 'T', cells])]). relacion([sujeto(['T', helper, 2, cells]), verbo([regulate]), complemento([inflammatory, responses, to, helminth, infections, while, also, mediating, pathological, processes, of, asthma, and, allergy])]). relacion([sujeto(['IL-4']), verbo([promotes]), complemento(['Th2', development, by, inducing, the, expression, of, the, 'GATA3', transcription, 'factor,', and, the, 'Th2', phenotype, is, stabilized, by, a, 'GATA3-dependent', autoregulatory, loop])]). relacion([sujeto(['In', this, 'study,', we]), verbo([found]), complemento([that, type, 'I', 'IFN', '(', 'IFN-alpha/beta)', blocked, human, 'Th2', development, and, inhibited, cytokine, secretion, from, committed, 'Th2', cells])]). relacion([sujeto(['This', negative, regulatory, pathway, was, operative, in, human, but, not, mouse, 'CD4(+)', 'T', cells, and, was, selective, to, type, 'I', 'IFN,', as, neither, 'IFN-gamma', nor, 'IL-12']), verbo([mediated]), complemento([such, inhibition])]). relacion([sujeto(['Thus,', we, demonstrate, a, novel, role, for, 'IFN-alpha/beta', in, blocking, 'Th2', 'cells,']), verbo([suggesting]), complemento([its, potential, as, a, promising, therapy, for, atopy, and, asthma])]). relacion([sujeto(['Recently,', marked, serum, 'IgG4', elevation, and, infiltration, of, 'IgG4-positive', plasmacytes, in, the, enlarged, exocrine, glands]), verbo([have]), complemento([been, reported, in, 'MD', patients])]). relacion([sujeto(['In', patients, with, 'IgG4-related', 'LGE,', mRNA, expression, of, 'IL-4,', 'IL-5,', 'IL-10', and, 'GATA-3', but, not, 'IFN-gamma', or, 'T-bet', was]), verbo([enhanced]), complemento([on, 'CD4+', 'T', cells, compared, with, that, in, healthy, controls])]). relacion([sujeto(['Th2', cells, may, be]), verbo([involved]), complemento([in, the, pathogenesis, of, 'IgG4-related', diseases])]). relacion([sujeto(['Special', 'AT-rich']), verbo([binding]), complemento([protein, 1, '(', 'SATB1)', is, a, global, chromatin, organizer, and, a, transcription, factor, regulated, by, 'interleukin-4', '(', 'IL-4)', during, the, early, 'T', helper, 2, '(', 'Th2)', cell, differentiation])]). relacion([sujeto(['Here', we, show, that, 'SATB1', controls, multiple, 'IL-4']), verbo([target]), complemento([genes, involved, in, human, 'Th', cell, polarization, or, function])]). relacion([sujeto(['Among', the, genes]), verbo([regulated]), complemento([by, 'SATB1', is, that, encoding, the, cytokine, 'IL-5,', which, is, predominantly, produced, by, 'Th2', cells, and, plays, a, key, role, in, the, development, of, eosinophilia, in, asthma])]). relacion([sujeto(['We', demonstrate, 'that,', during, the, early, 'Th2', cell, 'differentiation,', 'IL-5', expression, is, repressed, through, direct]), verbo([binding]), complemento([of, 'SATB1', to, the, 'IL-5', promoter])]). relacion([sujeto(['Our', results]), verbo([suggest]), complemento([that, a, competitive, mechanism, involving, 'SATB1', and, 'GATA3', regulates, 'IL-5', 'transcription,', and, provide, new, mechanistic, insights, into, the, stringent, regulation, of, 'IL-5', expression, during, human, 'Th2', cell, differentiation])]). relacion([sujeto(['This', study, aimed, to, investigate, the, immunological, mechanisms]), verbo([involved]), complemento([in, the, gender, distinct, incidence, of, paracoccidioidomycosis, '(', 'pcm),', an, endemic, systemic, mycosis, in, 'Latin', 'America,', which, is, at, least, 10, times, more, frequent, in, men, than, in, women])]). relacion([sujeto(['High', production, of, 'Th1', cytokines, and, 'T-bet', expression]), verbo([have]), complemento([been, detected, in, the, paracoccin, stimulated, cultures, of, spleen, cells, from, infected, female, mice])]). relacion([sujeto(['In', 'contrast,', in, similar, experimental, 'conditions,', cells, from, infected, males, produced, higher, levels, of, the, 'Th2', cytokines, and]), verbo([expressed]), complemento(['GATA-3'])]). relacion([sujeto(['Macrophages', from, male, and, female, mice, when]), verbo([stimulated]), complemento([with, paracoccin, displayed, similar, phagocytic, 'capability,', while, fungicidal, activity, was, two, times, more, efficiently, performed, by, macrophages, from, female, 'mice,', a, fact, that, was, associated, with, 50, '%', higher, levels, of, nitric, oxide, production])]). relacion([sujeto(['In', order, to, evaluate, the, role, of, sexual, hormones, in, the, observed, gender, 'distinction,', we]), verbo([have]), complemento([utilized, mice, that, have, been, submitted, to, gonadectomy, followed, by, inverse, hormonal, reconstitution])]). relacion([sujeto(['Spleen', cells, derived, from, castrated, males, reconstituted, with, estradiol]), verbo([have]), complemento([produced, higher, levels, of, 'IFN-gamma', '(', 1291, +, /, -, 15, 'pg/mL)', and, lower, levels, of, 'IL-10', '(', 494, +, /, -, 38, 'pg/mL),', than, normal, male, in, response, to, paracoccin, stimulus])]). relacion([sujeto(['In', 'conclusion,', our, results]), verbo([reveal]), complemento([that, the, sexual, hormones, had, a, profound, effect, on, the, biology, of, immune, 'cells,', and, estradiol, favours, protective, responses, to, 'P'])]). relacion([sujeto(['In', 'addition,', fungal, 'components,', such, as, 'paracoccin,', may]), verbo([provide]), complemento([additional, support, to, the, gender, dimorphic, immunity, that, marks, 'P'])]). relacion([sujeto(['Culturing', normal, renal, and, ccRCC, cells, in, differentiation, media, showed, that, only, ccRCC, cells, were]), verbo([induced]), complemento([to, undergo, adipogenic, 'and,', 'surprisingly,', osteogenic, differentiation])]). relacion([sujeto(['We']), verbo([suggest]), complemento([that, 'down-regulation', of, developmental, transcription, factors, may, mediate, the, aberrant, differentiation, in, ccRCC])]). relacion([sujeto(['Because', ccRCC, cells, grown, in, adipogenic, media, regain, the, characteristic, ccRCC, 'phenotype,', we]), verbo([have]), complemento([identified, a, new, in, vitro, ccRCC, cell, model, more, resembling, ccRCC, tumor, morphology])]). relacion([sujeto(['Interdependency', between, these, three, factors, in, breast, cancer, and, normal, mammary, development]), verbo([has]), complemento([been, 'suggested,', but, the, specific, role, for, 'FOXA1', is, not, known])]). relacion([sujeto(['Herein,', we]), verbo([report]), complemento([that, 'Foxa1', deficiency, causes, a, defect, in, 'hormone-induced', mammary, ductal, invasion, associated, with, a, loss, of, terminal, end, bud, formation, and, 'ERalpha', expression])]). relacion([sujeto(['By', 'contrast,', 'Foxa1', null, glands]), verbo([maintain]), complemento(['GATA3', expression])]). relacion([sujeto(['Using', breast, cancer, cell, 'lines,', we, also, demonstrate, that, 'FOXA1']), verbo([regulates]), complemento(['ERalpha', 'expression,', but, not, 'GATA3'])]). relacion([sujeto(['These', data]), verbo([reveal]), complemento([that, 'FOXA1', is, necessary, for, hormonal, responsiveness, in, the, developing, mammary, gland, and, 'ERalpha-positive', breast, 'cancers,', at, least, in, 'part,', through, its, control, of, 'ERalpha', expression])]). relacion([sujeto(['GATA-3,', a, transcription, 'factor,']), verbo([participates]), complemento([in, regulating, cell, 'development,', 'proliferation,', and, death])]). relacion([sujeto(['Such', protection]), verbo([involved]), complemento([enhancement, of, 'Bcl-X(L)', messenger, mRNA, and, protein, syntheses, and, the, translocation, of, this, antiapoptotic, protein, from, the, cytoplasm, to, mitochondria])]). relacion([sujeto(['Application', of, 'GATA-3', small, interfering, siRNA, into, osteoblasts]), verbo([decreased]), complemento([the, levels, of, this, transcription, factor, and, simultaneously, inhibited, 'Bcl-X(L)', mRNA, synthesis])]). relacion([sujeto(['Pretreatment', with, 'NO', lowered, the, oxidative, 'stress-caused', alteration, in, the]), verbo([binding]), complemento([of, 'GATA-3', to, its, specific, 'DNA', motifs])]). relacion([sujeto(['Oxidative', 'stress-inhibited', 'Runx2', mRNA, 'expression,', but, 'NO', preconditioning]), verbo([decreased]), complemento([such, inhibition])]). relacion([sujeto(['NO', pretreatment, 'time-dependently']), verbo([enhanced]), complemento([the, association, of, 'GATA-3', with, 'Runx2'])]). relacion([sujeto(['Knocking', down, the, translation, of, 'GATA-3', using, 'RNA', interference, significantly]), verbo([decreased]), complemento([the, protection, of, 'NO', preconditioning, against, oxidative, 'stress-induced', alterations, of, cell, 'morphologies,', 'DNA', 'fragmentation,', and, cell, apoptosis])]). relacion([sujeto(['In', 'comparison,', overexpression, of, 'GATA-3', could]), verbo([promote]), complemento(['NO', 'preconditioning-involved', 'Bcl-X(L)', expression, and, cell, survival])]). relacion([sujeto(['Therefore,', this, study, shows, that, 'GATA-3', plays, critical, roles, in]), verbo([mediating]), complemento([survival, signals, in, 'osteoblasts,', possibly, through, upregulating, 'bcl-x(L)', gene, expression])]). relacion([sujeto(['In', this, 'study,', we, demonstrate, that, native, 'Ag', trichosanthin, '(', 'Tk),', a, highly, purified, linear, peptide, isolated, from, a, 'Chinese', medicinal, 'herb,', is, able, to]), verbo([induce]), complemento([strong, suppression, of, 'OVA-specific', lymphoproliferation, at, low, concentrations, via, activation, of, 'IL-4/IL-10-secreting', 'CD8(+)CD28(-)', regulatory, 'T', cells, '(', 'Tregs)'])]). relacion([sujeto(['Moreover,', a, special, pattern, of, 'cytokine/transcription', factors, '(', 'IL-4(+)IL-10(+)IFN-gamma(-)Gata3(+)T-bet(-))', during]), verbo([suppressed]), complemento(['OVA-specific', 'T', cell, proliferation, was, observed, in, 'HS', 'C57BL/6', but, not, in, 'low-susceptible', 'C3H/He', mice])]). relacion([sujeto(['These', expanded, 'Tregs', were, able, to]), verbo([induce]), complemento([a, strong, inhibition, of, 'one-way', 'MLCs,', which, indicated, that, the, 'Tk-induced', hyporeaction, and, the, activation, of, 'CD8(+)CD28(-)', 'Tregs', might, be, under, the, influence, of, different, genetic, backgrounds])]). relacion([sujeto(['Additionally,', obvious, alterations, of, phenotypic, parameters, of, 'BDCs', after, 'Tk', stimulation, were, also, 'identified,', including]), verbo([enhanced]), complemento([production, of, 'IL-10,', decreased, secretion, of, 'IL-12,', and, detection, of, 'Jagged1,', a, 'Notch', ligand, on, 'BDCs'])]). relacion([sujeto(['Collectively,', our, data]), verbo([suggest]), complemento([that, the, changed, 'APC-related', factors, are, 'essential,', at, least, in, 'part,', for, the, activation, and, differentiation, of, 'Tk-induced', 'CD8(+)CD28(-)', 'Tregs'])]). relacion([sujeto(['Protein', kinase, 'C-theta', '(', 'PKC-theta)', is, important, for, the, activation, of, autoreactive, 'T', cells, but, is, thought, to, be, of, minor, importance, for, 'T-cell', responses, in, infectious, 'diseases,']), verbo([suggesting]), complemento([that, 'PKC-theta', may, be, a, target, for, the, treatment, of, 'T-cell-mediated', autoimmune, diseases])]). relacion([sujeto(['Adoptive', transfer, of, 'wild-type', 'CD4', plus, 'CD8', 'T', cells, significantly, protected, 'PKC-theta(-/-)', mice, from, death, by]), verbo([increasing]), complemento([the, numbers, of, gamma, 'interferon-producing', 'T'])]). relacion([sujeto(['Heterozygous', mutations, of, 'GATA3,', which, encodes, a, dual, 'zinc-finger', transcription, 'factor,']), verbo([cause]), complemento([hypoparathyroidism, with, sensorineural, deafness, and, renal, dysplasia])]). relacion([sujeto(['Here,', we]), verbo([have]), complemento([investigated, the, role, of, 'GATA3', in, parathyroid, function, by, challenging, 'Gata3+/-', mice, with, a, diet, low, in, calcium, and, vitamin, 'D', so, as, to, expose, any, defects, in, parathyroid, function])]). relacion([sujeto(['This']), verbo([led]), complemento([to, a, higher, mortality, among, 'Gata3+/-', mice, compared, with, 'Gata3+/+', mice])]). relacion([sujeto([5, ',', 'Gata3+/-', embryos, had, smaller, 'parathyroid-thymus', primordia, with, fewer, cells]), verbo([expressing]), complemento([the, 'parathyroid-specific', gene, glial, cells, missing, 2, '(', 'Gcm2),', the, homolog, of, human, 'GCMB'])]). relacion([sujeto(['Electrophoretic', mobility, 'shift,', luciferase, 'reporter,', and, chromatin, immunoprecipitation, assays, showed, that, 'GATA3']), verbo([binds]), complemento([specifically, to, a, functional, 'double-GATA', motif, within, the, 'GCMB', promoter])]). relacion([sujeto(['We']), verbo([report]), complemento([herein, mechanistic, details, concerning, the, role, of, these, transcription, factors, in, human, peripheral, blood, 'Th2', cell, development])]). relacion([sujeto(['Silencing', 'c-Myb', in, normal, human, naive, 'CD4(+)', cells, under, 'Th2', 'cell-promoting', conditions, blocked, 'up-regulation', of, 'GATA-3', and, 'interleukin-4,', and, in, 'effector/memory', 'CD4(+)', 'T', 'cells,']), verbo([decreased]), complemento([expression, of, 'GATA-3', and, 'Th2', cytokines])]). relacion([sujeto(['In', primary, 'T', 'cells,', 'c-Myb', allows, 'GATA-3', to, autoactivate, its, own, 'expression,', an, event, that]), verbo([requires]), complemento([the, direct, interaction, of, 'c-Myb', and, 'GATA-3', on, their, respective, binding, sites, in, promoter, of, 'GATA-3'])]). relacion([sujeto(['MLL', recruitment, into, the, 'c-Myb-GATA-3-Menin', complex, was]), verbo([associated]), complemento([with, the, formation, 'Th2', memory, cells])]). relacion([sujeto(['That', 'MLL-driven', epigenetic, changes, were, mechanistically, important, for, this, transition, was]), verbo([suggested]), complemento([by, the, fact, that, silencing, 'c-Myb', significantly, decreased, the, methylation, of, histone, 'H3K4', and, the, acetylation, of, histone, 'H3K9', at, the, 'GATA-3', locus, in, developing, 'Th2', and, 'CD4(+)', 'effector/memory', cells])]). relacion([sujeto(['Therefore,', 'c-Myb,', 'GATA-3,', and, 'Menin', form, a, core, transcription, complex, that]), verbo([regulates]), complemento(['GATA-3', expression, 'and,', with, the, recruitment, of, 'MLL,', 'Th2', cell, maturation, in, primary, human, peripheral, blood, 'T', cells])]). relacion([sujeto(['The', notion, that, family, support, may, buffer, individuals, under, adversity, from, poor, outcomes]), verbo([has]), complemento([been, theorized, to, have, important, implications, for, mental, and, physical, 'health,', but, little, is, known, about, the, biological, mechanisms, that, explain, these, links])]). relacion([sujeto(['We', hypothesized, that, adults, who, grew, up, in, low, socioeconomic, status, '(', 'SES)', households, but, who, experienced, high, levels, of, maternal, warmth, would, be, protected, from, the, 'pro-inflammatory', states, typically]), verbo([associated]), complemento([with, low, 'SES'])]). relacion([sujeto(['Low', 'early-life', 'SES', individuals, who, had, 'mothers,', who]), verbo([expressed]), complemento([high, warmth, toward, 'them,', exhibited, less, 'Toll-like', 'receptor-stimulated', production, of, interleukin, 6, ',', and, reduced, bioinformatic, indications, of, 'pro-inflammatory', transcription, factor, activity, '(', 'NF-κB)', and, immune, activating, transcription, factor, activity, '(', 'AP-1)', compared, to, those, who, were, low, in, 'SES', early, in, life, but, experienced, low, maternal, warmth])]). relacion([sujeto(['To', the, extent, that, such, effects, are, 'causal,', they]), verbo([suggest]), complemento([the, possibility, that, the, detrimental, immunologic, effects, of, low, 'early-life', 'SES', environments, may, be, partly, diminished, through, supportive, family, climates])]). relacion([sujeto(['It', was, hypothesized, that, the, suppressive, effect, of, diosgenin, '(', 1, ')', on, the, intestinal, 'T', helper, '(', 'Th)2', responses, is]), verbo([associated]), complemento([with, an, enhancement, of, the, regulatory, 'T-cell', immunity])]). relacion([sujeto(['Ovalbumin', '(', 'OVA)-sensitized', 'BALB/c', mice, were, gavaged, daily, with, 1, and, received, repeatedly, oral, 'OVA', challenges, to]), verbo([induce]), complemento([intestinal, allergic, responses])]). relacion([sujeto(['In', 'addition,', administration, of, 1, reversed, the, diminished, density, of, intestinal, 'Foxp3(+)', cells]), verbo([induced]), complemento([by, 'OVA', oral, challenges, and, enhanced, the, expression, of, 'IL-10', by, 'Foxp3(+)', cells, markedly])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, the, suppressive, effect, of, 1, on, 'allergen-induced', intestinal, 'Th2', responses, is, closely, associated, with, an, 'up-regulation', of, the, regulatory, 'T-cell', immunity, in, the, inflammatory, site])]). relacion([sujeto(['Immune', features, of, infants, with, food, allergy]), verbo([have]), complemento([not, been, delineated])]). relacion([sujeto(['We', sought, to, explore, the, basic, mechanisms, responsible, for, food, allergy, and, identify, 'biomarkers,', such, as, skin, prick, test, '(', 'SPT)', 'responses,', 'food-specific', 'IgE', 'levels,', and, mononuclear, cell, 'responses,', in, a, cohort, of, infants, with, likely, 'milk/egg', allergy, at]), verbo([increased]), complemento([risk, of, peanut, allergy])]). relacion([sujeto(['Mononuclear', cell, allergen, stimulation, screening, for, 'CD25,', 'cytokine-inducible', 'SH2-containing', protein, '(', 'CISH),', forkhead, box, protein, 3, '(', 'FOXP3),', 'GATA3,', 'IL10,', 'IL4,', 'IFNG,', and, 'T-box', transcription, factor, '(', 'TBET)', expression, by, using, 'casein,', egg, 'white,', and, peanut, revealed, that, only, 'allergen-induced', 'IL4', expression, was, significantly]), verbo([increased]), complemento([in, those, with, clinical, allergy, to, milk, '(', compared, with, nonallergic, 'subjects)', and, in, those, sensitized, to, 'peanut,', despite, the, absence, of, an, increase, in, 'GATA3', mRNA, expression])]). relacion([sujeto(['Infants', with, likely, 'milk/egg', allergy, are, at, considerably, high, risk, of, having]), verbo([increased]), complemento(['peanut-specific', 'IgE', levels, '(', potential, 'allergy)'])]). relacion([sujeto(['Absence', of, an]), verbo([increase]), complemento([in, 'GATA3', mRNA, expression, suggests, that, 'allergen-specific', 'IL-4', might, not, be, of, 'T-cell', origin])]). relacion([sujeto(['Results', showed, that, coadministration, of, 'OVA', with, paclitaxel]), verbo([induced]), complemento([significantly, higher, 'IgG,', 'IgG1,', 'IgG2a,', 'IgG2b,', 'IgG3', and, 'IgM', responses, than, when, 'OVA', was, used, alone])]). relacion([sujeto(['In', 'addition,', 'up-regulated', 'T-bet/GATA-3', together, with, significantly]), verbo([increased]), complemento([mRNA, expression, of, 'IL-4,', 'IL-10,', 'IFN-gamma', and, 'IL-12', by, 'splenocytes,', as, well, as, the, proliferative, responses, of, splenocytes, to, 'Con', 'A,', 'LPS', and, 'OVA', were, observed, in, 'paclitaxel-adjuvanted', groups])]). relacion([sujeto(['Incubation', of, a, murine, 'macrophage-like', cell, line, with, paclitaxel, significantly]), verbo([increased]), complemento(['TNF-alpha', and, -, 10, released, from, the, cells, and, expression, of, microRNAs, such, as, 'miR-155,', 'miR-147,', 'miR-146a', and, 'miR-132'])]). relacion([sujeto(['Therefore,', paclitaxel]), verbo([activated]), complemento([both, 'Th1', and, 'Th2', responses])]). relacion([sujeto(['Subsequently,', outer, cells, differentiate, into, trophectoderm, while, inner, cells]), verbo([retain]), complemento([pluripotency, to, become, inner, cell, mass, '(', 'ICM)', of, the, blastocyst])]). relacion([sujeto(['Elimination', of, zygotic, expression, of, 'trophectoderm-specific', transcription, factor, 'Cdx2']), verbo([leads]), complemento([to, defects, in, the, maintenance, of, the, blastocyst, 'cavity,', suggesting, that, it, participates, only, in, the, late, stage, of, trophectoderm, formation])]). relacion([sujeto(['However,', we, now]), verbo([find]), complemento([that, mouse, embryos, also, have, a, maternally, provided, pool, of, 'Cdx2', mRNA])]). relacion([sujeto(['Moreover,', depletion, of, both, maternal, and, zygotic, 'Cdx2', from, immediately, after, fertilization, by, three, independent, 'approaches,', 'dsRNAi,', siRNAi, and, morpholino, 'oligonucleotides,']), verbo([leads]), complemento([to, developmental, arrest, at, much, earlier, stages, than, expected, from, elimination, of, only, zygotic, 'Cdx2'])]). relacion([sujeto(['This', developmental]), verbo([arrest]), complemento([is, associated, with, defects, in, cell, 'polarisation,', reflected, by, expression, and, localisation, of, cell, polarity, molecules, such, as, 'Par3', and, aPKC, and, cell, compaction, at, the, 8, -, and, 16, -, cell, stages])]). relacion([sujeto(['Cells', deprived, of, 'Cdx2', show, delayed, development, with]), verbo([increased]), complemento([cell, cycle, 'length,', irregular, cell, division, and, increased, incidence, of, apoptosis])]). relacion([sujeto(['Taken', 'together,', our, results, indicate, that, 'Cdx2']), verbo([participates]), complemento([in, two, steps, leading, to, trophectoderm, 'specification:', appropriate, polarisation, of, blastomeres, at, the, 8, -, and, 16, -, cell, stage, and, then, the, maintenance, of, trophectoderm, 'lineage-specific', differentiation])]). relacion([sujeto(['Previous', studies]), verbo([have]), complemento([demonstrated, that, the, proteasome, 'inhibitor,', 'lactacystin,', suppresses, cytokine, production, and, induction, of, other, inflammatory, mediators, by, 'LPS-stimulated', macrophages])]). relacion([sujeto(['The', purpose, of, the, present, studies, was, to, determine, the, effect, of, lactacystin, upon, the, function, of]), verbo([activated]), complemento([human, 'Jurkat', 'T', cells, and, murine, splenocytes])]). relacion([sujeto(['Lactacystin', treatment]), verbo([suppressed]), complemento([interleukin, '(', 'IL)-2,', interferon, '(', 'IFN)gamma,', and, 'IL-13', production, similarly, in, both, activated, 'Jurkat', cells, and, primary, splenocytes])]). relacion([sujeto(['While', lactacystin]), verbo([inhibited]), complemento(['IL-4', mRNA, transcription, in, primary, 'splenocytes,', it, induced, 'IL-4', mRNA, in, a, 'concentration-dependent', manner, in, 'Jurkat', cells])]). relacion([sujeto(['The']), verbo([increase]), complemento([in, 'IL-4', mRNA, levels, by, lactacystin, did, not, correlate, with, increases, in, 'T(H2)-specific', transcription, 'factors,', avian, musculoaponeurotic, fibrosarcoma, 'AS42', oncogene, homolog, '(', 'c-maf)', or, 'GATA', binding, protein, 3, '(', 'GATA-3)'])]). relacion([sujeto(['In', 'addition,', the]), verbo([binding]), complemento([of, both, 'GATA-3', and, 't-bet', to, their, respective, response, elements, was, essentially, unchanged, by, lactacystin, treatment, in, both, splenocytes, and, 'Jurkat', 'T', 'cells,', suggesting, the, induction, of, 'IL-4', is, due, to, other, mechanisms])]). relacion([sujeto(['Collectively,', the, current, studies]), verbo([suggest]), complemento([proteasomal, activity, has, differential, effects, on, 'IL-4', transcription, in, activated, 'Jurkat', cells, and, primary, splenocytes])]). relacion([sujeto(['Chromosome', 10, p, terminal, deletions]), verbo([have]), complemento([been, associated, with, 'DiGeorge', 'phenotype,', and, within, the, same, genomic, region, haploinsufficiency, of, 'GATA3', causes, the, 'HDR', syndrome, '(', 'hypoparathyroidism,', sensorineural, 'deafness,', renal, 'dysplasia)'])]). relacion([sujeto(['We']), verbo([have]), complemento([performed, detailed, molecular, analysis, of, four, patients, with, partial, overlapping, 10, p, deletions, by, using, 'FISH-mapping,', 'array-CGH,', and, 'custom-designed', 'high-resolution', oligonucleotide, array])]). relacion([sujeto(['The', combined, information, of, present, and, previous, cases]), verbo([suggests]), complemento([that, partial, deletions, of, 10, 'p14-p15', represent, a, syndrome, with, a, distinct, and, more, severe, phenotype, than, previously, assumed])]). relacion([sujeto(['A', critical, region]), verbo([involved]), complemento([in, mental, retardation, and, speech, impairment, is, defined, within, 1.6, 'Mb', in, 10, p15])]). relacion([sujeto(['In', 'addition,', deletion, of, 4.3, 'Mb', within, 10, p14, is]), verbo([associated]), complemento([with, autism, and, characteristic, clinical, findings])]). relacion([sujeto(['Extraembryonic', tissues]), verbo([have]), complemento([various, roles, in, 'protecting,', nourishing, and, patterning, embryos])]). relacion([sujeto(['Prior', to, gastrulation, in, 'zebrafish,', the, yolk, syncytial, layer, -, an, extraembryonic]), verbo([nuclear]), complemento([syncytium, -, produces, signals, that, induce, mesoderm, and, endoderm, formation])]). relacion([sujeto(['We', hypothesize, that, key, components, of, the, yolk, syncytial, 'layer\'s', mesoderm, and, endoderm]), verbo([inducing]), complemento([activity, are, expressed, as, mRNAs, in, the, 'E-YSL'])]). relacion([sujeto(['To', identify, genes]), verbo([expressed]), complemento([in, the, 'E-YSL,', we, used, microarrays, to, compare, the, transcription, profiles, of, intact, 'pre-gastrula', embryos, with, 'pre-gastrula', embryonic, cells, that, we, had, separated, from, the, yolk, and, yolk, syncytial, layer])]). relacion([sujeto(['We']), verbo([have]), complemento([devised, an, effective, strategy, for, enriching, and, identifying, genes, expressed, in, the, 'E-YSL', of, 'pre-gastrula', embryos])]). relacion([sujeto(['To', our, 'surprise,', maternal, genes, and, genes]), verbo([expressed]), complemento([in, the, 'EVL', were, also, enriched, by, this, strategy])]). relacion([sujeto(['Genetic', and, epigenetic, programming, of, 'T', helper, '(', 'Th)', cell, subsets, during, their, polarization, from, naive, 'Th', cells, establishes, 'long-lived', memory, 'Th', cells, that, stably]), verbo([maintain]), complemento([their, lineage, signatures])]). relacion([sujeto(['In', this, 'study,', we, show, that, 'Ag-specific', memory, 'Th', cells, were, redifferentiated, into, 'Foxp3(+)', 'T', cells, by, 'TGF-beta', when]), verbo([stimulated]), complemento([in, the, presence, of, 'all-trans', retinoic, acid, and, rapamycin])]). relacion([sujeto(['Instead,', the, converted, 'Foxp3(+)', 'T', cells]), verbo([suppressed]), complemento([the, proliferation, and, cytokine, production, of, 'Th2', memory, cells])]). relacion([sujeto(['More', 'importantly,', the, converted, 'Foxp3(+)', 'T', cells, efficiently, accumulated, in, the, airways, and, significantly]), verbo([suppressed]), complemento(['Th2', memory, 'cell-mediated', airway, 'hyperreactivity,', 'eosinophilia,', and, 'allergen-specific', 'IgE', production])]). relacion([sujeto(['Our', findings]), verbo([reveal]), complemento([the, plasticity, of, 'Th2', memory, cells, and, provide, a, strategy, for, adoptive, immunotherapy, for, the, treatment, of, allergic, diseases])]). relacion([sujeto(['Allergic', asthma, is]), verbo([associated]), complemento([with, eosinophilic, inflammation, in, the, airways])]). relacion([sujeto(['Allergen', challenge, with, ovalbumin]), verbo([induced]), complemento([comparable, eosinophilia, in, bone, marrow, '(', 'BM),', blood, and, lung, tissue, in, both, strains, of, mice, compared, to, 'phosphate-buffered', saline, 'controls,', which, was, confirmed, by, immunocytochemistry])]). relacion([sujeto(['There', was, a, small]), verbo([increase]), complemento([in, the, number, of, lung, 'MBP+BrdU(-)', eosinophils, in, 'C57BL/6', mice, compared, to, 'BALB/c', 'mice,', which, suggests, a, basal, increase, in, this, strain, following, sensitization])]). relacion([sujeto(['(', 2010, ')', describe, the, opposing, effects, of, transcription, factors, 'Runx3', and, 'GATA3', in, the, network]), verbo([promoting]), complemento(['T', helper, 1, cell, development])]). relacion([sujeto(['At', this, 'stage,', transcription, factor, 'Cdx2', represses, pluripotency, 'genes,', thus]), verbo([promoting]), complemento([extraembryonic, trophoblast, fate])]). relacion([sujeto(['Recently,', transcription, factor, 'Gata3', was, shown, to]), verbo([act]), complemento([in, a, parallel, pathway, in, promoting, trophoblast, cell, 'fate,', suggesting, that, there, are, more, factors, working, in, the, trophoblast, lineage])]). relacion([sujeto(['Here,', we]), verbo([report]), complemento([that, the, transcription, factor, 'Tcfap2c', is, expressed, at, a, high, level, in, the, trophectoderm, and, is, able, to, induce, trophoblast, fate, in, embryonic, stem, cells])]). relacion([sujeto(['Trophoblast', fate]), verbo([induced]), complemento([by, 'Tcfap2c', does, not, require, 'Cdx2', and, vice, 'versa,', suggesting, that, the, molecules, act, in, alternative, pathways])]). relacion([sujeto(['However,', both, 'Tcfap2c', and, 'Cdx2', are]), verbo([required]), complemento([for, the, upregulation, of, 'Elf5,', a, marker, of, trophoblast, stem, cell, 'maintenance,', suggesting, that, both, factors, are, required, for, stable, trophoblast, induction])]). relacion([sujeto(['Tcfap2c-controlled', trophoblast, maintenance]), verbo([involves]), complemento([the, induction, of, 'Cdx2', and, the, repression, of, the, pluripotency, factor, 'Nanog'])]). relacion([sujeto(['Taken', 'together,', these, observations]), verbo([suggest]), complemento([that, 'Tcfap2c', and, 'Cdx2', cooperate, to, override, the, pluripotency, program, and, establish, the, extraembryonic, trophoblast, maintenance, program, in, murine, embryos])]). relacion([sujeto(['Another', 'T-box-containing', transcription, factor, 'Eomes,', but, not, 'T-bet,', was]), verbo([induced]), complemento([both, in, 'GATA3-deficient', 'CD4(+)', 'T', cells, differentiated, under, 'Th2', cell, conditions, and, in, 'Th2', cells, with, enforced, 'Runx3', 'expression,', contributing, to, 'IFN-gamma', production])]). relacion([sujeto(['GATA3', overexpression, blocked, 'Runx3-mediated', 'Eomes', induction, and, 'IFN-gamma', 'production,', and, 'GATA3', protein, physically]), verbo([interacted]), complemento([with, 'Runx3', protein])]). relacion([sujeto(['Furthermore,', we]), verbo([found]), complemento([that, 'Runx3', directly, bound, to, multiple, regulatory, elements, of, the, 'Ifng', gene, and, that, blocking, 'Runx3', function, in, either, 'Th1', or, 'GATA3-deficient', &, 'quot;Th2"', cells, results, in, diminished, 'IFN-gamma', production, by, these, cells])]). relacion([sujeto(['Thus,', the, 'Runx3-mediated', 'pathway,', actively]), verbo([suppressed]), complemento([by, 'GATA3,', induces, 'IFN-gamma', production, in, a, 'STAT4-', and, 'T-bet-independent', manner])]). relacion([sujeto(['The', dynamic, composition, of, transcription, factors]), verbo([acting]), complemento([within, a, given, 'T', cell, drive, clonal, expansion, and, specify, differentiation, into, a, growing, array, of, effector, and, regulatory, 'T', cell, subsets])]). relacion([sujeto(['The', plasma, level, of, 'IFN-γ', was]), verbo([increased]), complemento([significantly, in, the, pharmacological, group, rats, when, compared, with, the, value, of, control, group, rats, '(', t, =, 4.61, ',', 'P', &, 'lt;', 0.05, ')', and, with, the, negative, control, group, '(', t, =, 5.79, ',', 'P', &, 'lt;', 0.05, ')', ',', respectively])]). relacion([sujeto(['Relative', quantization, of, expression, of, 'GATA-3', in, the, control, group, rats, was, significantly, higher, than, that, in, the, negative, control, group, and, pharmacological, group, rats, '(', 'chi²', value, were, 10.113, and, 2.384, ',', 'respectively,', all, 'P', &, 'lt;', 0.05, ')', ',', and, that, of, 'GATA-3', in, the, pharmacological, group, rats, was]), verbo([increased]), complemento([as, compared, to, the, negative, control, group, rats, '(', 'chi²', =, 3.784, ',', 'P', &, 'lt;', 0.05, ')'])]). relacion([sujeto(['Although', 'cell-to-cell', variability]), verbo([has]), complemento([been, recognized, as, an, unavoidable, consequence, of, stochasticity, in, gene, 'expression,', it, may, also, serve, a, functional, role, for, tuning, physiological, responses, within, a, cell, population])]). relacion([sujeto(['In', the, immune, 'system,', remarkably, large, variability, in, the, expression, of, cytokine, genes]), verbo([has]), complemento([been, observed, in, homogeneous, populations, of, 'lymphocytes,', but, the, underlying, molecular, mechanisms, are, incompletely, understood])]). relacion([sujeto(['We', show, that, a, stochastic, 'rate-limiting', step, upstream, of, transcription, 'initiation,', but]), verbo([acting]), complemento([at, the, level, of, an, individual, 'allele,', controls, il4, expression])]). relacion([sujeto(['We', support, this]), verbo([finding]), complemento([by, experimental, evidence, of, a, previously, unknown, 'short-term', memory, that, was, predicted, by, the, model, to, arise, from, the, long, lifetime, of, the, active, state])]). relacion([sujeto(['Our', analysis, shows, how, a, stochastic, mechanism]), verbo([acting]), complemento([at, the, chromatin, level, can, be, integrated, with, transcriptional, regulation, to, quantitatively, control, 'cell-to-cell', variability])]). relacion([sujeto(['The', iNKT, cells, derive, from, 'CD4(+)CD8(+)', 'double-positive', '(', 'DP)', 'thymocytes,', and, their, generation]), verbo([requires]), complemento([a, long, 'half-life', of, 'DP', thymocytes, to, allow, 'V(alpha)14-J(alpha)18', 'rearrangements,', expression, of, 'glycolipid-loaded', 'CD1d', on, 'DP', 'thymocytes,', and, signaling, through, the, 'signaling-activation', molecule, 'SLAM-adaptor', 'SAP', pathway])]). relacion([sujeto(['Here', we, show, that, the, transcription, factor, 'c-Myb']), verbo([has]), complemento([a, central, role, in, priming, 'DP', thymocytes, to, enter, the, iNKT, lineage, by, simultaneously, regulating, 'CD1d', 'expression,', the, 'half-life', of, 'DP', cells, and, expression, of, 'SLAMF1,', 'SLAMF6', and, 'SAP'])]). relacion([sujeto(['First,', tyrosine, hydroxylase, '(', 'TH)', expression, was]), verbo([stimulated]), complemento([in, 'pre-existing', dopa, decarboxylase, immunoreactive, neurons, and, several, 'TH-relevant', transcription, factors, '(', 'Gata2,', 'Gata3,', 'Creb1,', 'Crebbp)', were, 'up-regulated'])]). relacion([sujeto(['Fourth,', 9, -, 'me-BC']), verbo([inhibited]), complemento([the, proliferation, of, microglia, induced, by, toxin, treatment, and, installed, an, 'anti-inflammatory', environment, by, decreasing, the, expression, of, inflammatory, cytokines, and, receptors])]). relacion([sujeto(['Interleukin-13', '(', 'IL-13)', is]), verbo([recognized]), complemento([to, be, a, key, modulator, in, the, pathogenesis, of, 'Th2-induced', allergic, inflammation])]). relacion([sujeto(['Transcription', factors, 'GATA3', and, 'NFAT1']), verbo([have]), complemento([been, both, implicated, in, the, regulation, of, 'Th2', cytokines])]). relacion([sujeto(['Cells', were]), verbo([stimulated]), complemento([with, 'anti-CD3', plus, 'anti-CD28', antibodies, to, mimic, in, vivo, 'antigen-mediated', 'co-stimulation;', the, expression, of, 'IL-13', mRNA, was, determined, by, 'real-time', 'PCR;', chromation, immunoprecipitation, '(', 'CHIP)', assay, was, employed, to, investigate, the, 'NFAT1', binding, to, 'IL-13', promoter])]). relacion([sujeto(['GATA3', siRNA]), verbo([suppressed]), complemento([the, expression, of, 'GATA3', both, in, mRNA, and, protein, levels, in, 'Hut-78', cells])]). relacion([sujeto(['The']), verbo([binding]), complemento([of, 'NFAT1', to, 'IL-13', promoter, was, inhibited, by, 'GATA3', siRNA, in, activated, 'T', 'cells,', which, was, followed, by, the, reduction, of, 'IL-13', transcription])]). relacion([sujeto(['Increased', numbers, of, eosinophils, in, the, airways, of, female, mice, after, antigen, challenge, was]), verbo([associated]), complemento([with, increased, levels, of, 'T', helper, '(', 'Th)2', cytokines, at, the, site, of, 'inflammation,', and, in, human, and, mouse, 'studies,', the, profile, of, cytokines, produced, by, immune, cells, from, women, showed, greater, 'Th2', predominance])]). relacion([sujeto(['Greater', 'antigen-induced', 'Th2', cytokine, production, by, bronchial, lymph, node, cells, from, female, mice, was]), verbo([associated]), complemento([with, enhanced, 'Th2', cell, differentiation, and, increased, expression, of, the, 'Th2-specific', transcription, 'factor,', 'GATA-3'])]). relacion([sujeto(['The', regulation, of, autoimmune, diseases]), verbo([mediated]), complemento([by, 'Th1', and, 'Th17', cells, by, 'Tregs', has, been, studied, and, reviewed, extensively])]). relacion([sujeto(['However,', much, less]), verbo([has]), complemento([been, presented, about, the, interplay, between, 'Tregs', and, 'Th2', cells, and, their, contribution, to, allergic, disease])]). relacion([sujeto(['Psoriasis', is, considered, as, a, 'T', 'cell-mediated', autoimmune, 'disease,', and, the, 'Th1', response]), verbo([has]), complemento([been, established, as, the, major, immune, agent, in, its, pathomechanisms])]). relacion([sujeto(['The', relative, expression, of, 'Th1', and, 'Th2', transcription, 'factors,', 'T-bet', and, 'GATA-3,', resulting, in, a, swing, in, the, 'Th1/Th2', 'pendulum,']), verbo([has]), complemento([been, implicated, in, a, number, of, immunological, diseases])]). relacion([sujeto(['However,', their, expression, and, correlation, with, psoriasis]), verbo([has]), complemento([not, yet, been, studied])]). relacion([sujeto(['We', also, observed, a, significant]), verbo([increase]), complemento([in, 'CD4+', cells, and, 'T-bet', positive, cells, in, psoriatic, lesions])]). relacion([sujeto(['These', results]), verbo([suggested]), complemento([that, 'T-bet', and, 'GATA-3', might, be, regulator, genes, for, psoriasis, via, the, 'Th1/Th2', 'balance,', and, the, 'Th1-specific', transcription, 'factor,', 'T-bet,', may, play, an, important, role, in, the, development, and, maintenance, of, psoriasis])]). relacion([sujeto(['Each', of, these, 'Th-lineages']), verbo([has]), complemento([specific, functions, in, immune, defense, and, 'T', cell, homeostasis])]). relacion([sujeto(['Our', analysis]), verbo([targeted]), complemento([the, identification, of, new, regulatory, transcription, factor, binding, sites, '(', 'TFBSs)', in, the, promoter, regions, of, 'up-', and, 'down-regulated', genes, in, 'Treg', cell, differentiation, and, lineage, maintenance])]). relacion([sujeto(['Results', of, our, analysis]), verbo([suggest]), complemento([that, 'Ets', and, 'IRF', family, members, contribute, to, the, regulation, of, the, initial, induction, of, 'Treg', cells])]). relacion([sujeto(['Interestingly,', previous, studies]), verbo([have]), complemento([observed, functional, interactions, of, both, 'TFBS-pairs', in, 'T', cells])]). relacion([sujeto(['This', study]), verbo([provides]), complemento([a, starting, point, for, further, investigations, to, elucidate, the, transcriptional, network, in, 'Treg', cells])]). relacion([sujeto(['The', 'Src', family, kinase, 'Lck']), verbo([has]), complemento([been, shown, to, be, crucial, in, 'T', cell, signaling, and, development])]). relacion([sujeto(['Lck']), verbo([has]), complemento([previously, been, shown, to, play, a, role, in, the, cytokine, expression, of, 'Th2', 'cells,', but, the, mechanism, by, which, 'Lck', influences, 'Th2', effector, functions, is, unknown])]). relacion([sujeto(['Using', a, mouse, 'model,', we]), verbo([report]), complemento([that, 'Lck', is, important, in, regulating, the, expression, of, 'IL-4', in, 'Th2', skewed, cells, but, is, not, as, necessary, for, the, expression, of, 'Th2', cytokines, 'IL-5,', 'IL-10,', and, 'IL-13'])]). relacion([sujeto(['Moreover,', this, atypical, expression, pattern, of, 'T-bet', and, 'GATA-3', correlates, with]), verbo([increased]), complemento([histone, 3, acetylation, at, the, 'Ifng', locus, and, production, of, the, 'Th1', cytokine, 'IFN-gamma'])]). relacion([sujeto(['We']), verbo([find]), complemento([overexpression, of, 'GATA-3', restores, 'IL-4', expression, in, 'lck(-/-)', 'Th2', 'cells;', this, indicates, that, the, decreased, 'IL-4', expression, is, due, in, part, to, reduced, amounts, of, 'GATA-3'])]). relacion([sujeto(['Taken', 'together,', these, data, imply, that, 'Lck']), verbo([mediates]), complemento(['Th2', differentiation, through, effects, on, 'T-bet', and, 'GATA-3'])]). relacion([sujeto(['Previous', studies]), verbo([have]), complemento([indicated, that, 'T-helper', immune, response, is, the, critical, host, factor, for, susceptibility, to, 'Candida', infection])]). relacion([sujeto(['Candida', outgrowth, was, significantly]), verbo([increased]), complemento([in, the, kidneys, of, 'GATA-3-overexpressing', 'mice,', compared, with, 'wild-type', mice])]). relacion([sujeto(['Exogenous', administration, of, gamma, interferon, to, 'GATA-3-overexpressing', mice, significantly, reduced, 'Candida', outgrowth, in, the, kidney, and, thus]), verbo([increased]), complemento([the, survival, rate])]). relacion([sujeto(['Administration', of, gamma, interferon, also]), verbo([increased]), complemento([the, recruitment, of, macrophages, into, the, peritoneal, cavity, in, response, to, 'Candida', infection])]). relacion([sujeto(['These', results, indicate, that, overexpression, of, 'GATA-3']), verbo([modulates]), complemento([macrophage, antifungal, activity, and, thus, enhances, the, susceptibility, to, systemic, 'Candida', 'infection,', possibly, by, reducing, the, production, of, gamma, interferon, in, response, to, 'Candida', infection])]). relacion([sujeto(['A', dramatic]), verbo([decrease]), complemento([in, circulating, lymphocyte, number, is, regularly, described, after, septic, shock])]). relacion([sujeto(['Gene', expression, analysis, of, transcription, factors, specific, for, 'TH1,', 'TH2,', 'CD4CD25', 'regulatory,', and, 'TH17', lymphocytes, showed, a, severe]), verbo([decrease]), complemento([in, comparison, with, healthy, 'individuals\'', values])]). relacion([sujeto(['At', the, time, of, diagnosis, of, shock, and, admission, in, the, intensive, care, 'unit,', septic, patients, already, present, with, severe, lymphopenia]), verbo([involving]), complemento([every, lymphocyte, subsets, including, 'CD4', 'T-cell', subpopulations])]). relacion([sujeto(['Loss', of, transforming, growth, 'factor-beta', receptor, 'III', '(', 'TbetaRIII)', correlates, with]), verbo([loss]), complemento([of, transforming, growth, 'factor-beta', '(', 'TGF-beta)', responsiveness, and, suggests, a, role, for, dysregulated, 'TGF-beta', signaling, in, clear, cell, renal, cell, carcinoma, '(', 'ccRCC)', progression, and, metastasis])]). relacion([sujeto(['We']), verbo([find]), complemento([that, this, loss, of, expression, is, not, due, to, methylation, of, the, gene, and, we, define, 'GATA3', as, the, first, transcriptional, factor, to, positively, regulate, 'TbetaRIII', expression, in, human, cells])]). relacion([sujeto(['We', localize, 'GATA3\'s']), verbo([binding]), complemento([to, a, 10, -, bp, region, of, the, 'TbetaRIII', proximal, promoter])]). relacion([sujeto(['We', demonstrate, that, 'GATA3', mRNA, is, downregulated, in, all, 'stages,', of, 'ccRCC,', mechanistically, show, that, 'GATA3', is, methylated, in, ccRCC, patient, tumor, tissues, as, well, as, cell, 'lines,', and, that]), verbo([inhibiting]), complemento(['GATA3', expression, in, normal, renal, epithelial, cells, downregulates, 'TbetaRIII', mRNA, and, protein, expression])]). relacion([sujeto(['These', data, support, a, sequential, model, whereby]), verbo([loss]), complemento([of, 'GATA3', expression, through, epigenetic, silencing, decreases, 'TbetaRIII', expression, during, ccRCC, progression])]). relacion([sujeto(['Gastric', cancer, is, a, serious, public, health, cancer, and]), verbo([causes]), complemento([nearly, 1, million, deaths, a, year, worldwide])]). relacion([sujeto(['Polymorphisms']), verbo([have]), complemento([also, been, shown, to, exist, in, 'T-bet'])]). relacion([sujeto(['Some']), verbo([reports]), complemento([indicated, that, some, tumours, were, associated, with, the, drift, of, 'Th1', and, 'Th2'])]). relacion([sujeto(['T-bet', gene, mutations, may, be]), verbo([associated]), complemento([with, 'Th2-dominated', condition, in, gastric, cancers])]). relacion([sujeto(['All', tissues, were, assessed, for, eosinophil, and, mast, cell, numbers, by, 'immunohistochemistry;', 'IL-5,', 'ECP', and, 'IgE', concentrations, by, 'immunoassay;', mRNA, for, transcription, factors, 'GATA-3,', 'T-bet,', 'FOXP3', and, 'RORc', by, quantitative, 'real-time', polymerase, chain, 'reaction;', and, 'IgE-induced']), verbo([release]), complemento([of, 'LTC(4)/D(4)/E(4)', and, 'PGD(2)in', vitro])]). relacion([sujeto(['Eosinophils', and, mast, cells, were, significantly]), verbo([increased]), complemento([in, patients, with, 'PER', and, patients, with, 'IAR', compared, to, control, 'subjects;', by, patients, with, 'PER', demonstrating, even, significantly, greater, increase, of, both, cell, types, than, patients, with, 'IAR'])]). relacion([sujeto(['Similarly,', 'ECP', 'IL-5,', 'GATA-3', mRNA, expression, and, 'IgE-induced']), verbo([release]), complemento([of, 'LTC4/D(4)/E(4)', and, 'PGD(2)', from, mast, cells, were, significantly, increased, in, patients, with, 'PER', compared, to, patients, with, 'IAR'])]). relacion([sujeto(['The', findings, from, the, present, study]), verbo([suggest]), complemento([that, 'PER', is, characterized, by, a, significantly, greater, eosinophilic, and, predominantly, 'Th2', 'cell-mediated', nasal, inflammatory, profile, compared, to, 'IAR'])]). relacion([sujeto(['GATA3,', a, transcription, factor, that]), verbo([regulates]), complemento(['T', lymphocyte, differentiation, and, 'maturation,', is, exclusively, expressed, in, early, stage, well, differentiated, breast, cancers, but, not, in, advanced, invasive, cancers])]). relacion([sujeto(['Ectopic', expression, of, 'GATA3', in, 'MDA-MB-231', cells]), verbo([led]), complemento([to, a, 'cuboidal-like', epithelial, phenotype, and, reduced, cell, invasive, activity])]). relacion([sujeto(['These', cells, also]), verbo([increased]), complemento(['E-cadherin', expression, but, decreased, levels, of, 'vimentin,', 'N-cadherin,', and, 'MMP-9'])]). relacion([sujeto(['Further,', 'MDA-MB-231', cells]), verbo([expressing]), complemento(['GATA3', grew, smaller, primary, tumors, without, metastasis, compared, with, larger, metastatic, tumors, derived, from, control, 'MDA-MB-231', cells, in, xenografted, mice])]). relacion([sujeto(['GATA3', was]), verbo([found]), complemento([to, induce, 'E-cadherin', expression, through, binding, 'GATA-like', motifs, located, in, the, 'E-cadherin', promoter])]). relacion([sujeto(['Blockade', of, 'GATA3', using, small, interfering, 'RNA', gene, knockdown, in, 'MCF-7', cells]), verbo([triggered]), complemento([fibroblastic, transformation, and, cell, 'invasion,', resulting, in, distant, metastasis])]). relacion([sujeto(['These', data]), verbo([suggest]), complemento([that, 'GATA3', drives, invasive, breast, cancer, cells, to, undergo, the, reversal, of, 'epithelial-mesenchymal', 'transition,', leading, to, the, suppression, of, cancer, metastasis])]). relacion([sujeto(['Recently,', 'all-trans', retinoic, acid]), verbo([has]), complemento([been, shown, that, can, lead, 'T-cell', response, by, suppressing, 'Th17', development, via, retinoic, acid, receptor, '(', 'RAR),', but, it, is, still, unknown, whether, 'all-trans', retinoic, acid, can, modulate, 'Th1', response, of, inflammatory, bowel, disease])]). relacion([sujeto(['All-trans', retinoic, acid, treatment]), verbo([inhibited]), complemento([inflammatory, responses, as, shown, by, lower, histological, inflammatory, scores, and, 'MPO', 'activity,', compared, with, 'LE135', and, medium, groups])]). relacion([sujeto(['Furthermore,', in, 'LPMCs', culture, 'supernatants,', the, levels, of, 'Th1', cytokines, '(', 'INF-gamma,', 'IL-12,', and, 'TNF-alpha)', were]), verbo([decreased]), complemento([while, those, of, 'Th2', cytokines, '(', 'IL-4', and, 'IL-10)', were, increased, significantly, in, 'all-trans', retinoic, 'acid-treated', mice])]). relacion([sujeto(['In', 'addition,', 'T-bet', expression, in, 'LPMCs', was]), verbo([inhibited]), complemento([and, 'GATA-3', expression, was, 'up-regulated', in, 'all-trans', retinoic, acidtreated, mice])]). relacion([sujeto(['By', shifting, 'Th1', to, 'Th2', profile, in, inflamed, 'mucosa,', 'all-trans', retinoic, acid, 'down-regulates', inflammatory, response, and, ameliorates, acute, 'TNBS-induced', 'colitis,', which]), verbo([suggests]), complemento([the, ligand, of, 'RAR-alpha-based', pharmaceutical, strategies, for, managing, inflammatory, bowel, disease])]). relacion([sujeto(['Trophoblast', stem, cells, '(', 'TS', 'cells),', derived, from, the, trophectoderm, '(', 'TE)', of, 'blastocysts,']), verbo([require]), complemento([transcription, factors, '(', 'TFs)', and, external, signals, '(', 'FGF4,', 'INHBA/NODAL/TGFB1)', for, 'self-renewal'])]). relacion([sujeto(['While', many]), verbo([reports]), complemento([have, focused, on, 'TF', networks, that, regulate, embryonic, stem, cell, '(', 'ES', 'cell)', 'self-renewal', and, 'pluripotency,', little, is, know, about, 'TF', networks, that, regulate, 'self-renewal', in, 'TS', cells])]). relacion([sujeto(['To', further, understand, transcriptional, networks, in, 'TS', 'cells,', we, used, chromatin, immunoprecipitation, with, 'DNA', microarray, hybridization, '(', 'ChIP-chip)', analysis, to, investigate]), verbo([targets]), complemento([of, the, 'TFs-TCFAP2C,', 'EOMES,', 'ETS2,', and, 'GATA3-and', a, chromatin, remodeling, 'factor,', 'SMARCA4'])]). relacion([sujeto(['We', then, evaluated, the, transcriptional, states, of]), verbo([target]), complemento([genes, using, transcriptome, analysis, and, 'genome-wide', analysis, of, histone, 'H3', acetylation, '(', 'AcH3)'])]). relacion([sujeto(['Our', results, describe, previously, unknown, transcriptional, networks, in, 'TS', 'cells,', including, 'TF', occupancy, of, genes]), verbo([involved]), complemento([in, 'ES', cell, 'self-renewal', and, 'pluripotency,', 'co-occupancy', of, 'TCFAP2C,', 'SMARCA4,', and, 'EOMES', at, a, significant, number, of, 'genes,', and, transcriptional, regulatory, circuitry, within, the, five, factors])]). relacion([sujeto(['Moreover,', 'RNAi', depletion, of, 'Tcfap2c,', 'Smarca4,', and, 'Eomes', transcripts, resulted, in, a]), verbo([loss]), complemento([of, normal, colony, morphology, and, 'down-regulation', of, 'TS', 'cell-specific', 'genes,', suggesting, an, important, role, for, 'TCFAP2C,', 'SMARCA4,', and, 'EOMES', in, 'TS', cell, 'self-renewal'])]). relacion([sujeto(['Through', 'genome-wide', mapping, and, global, expression, analysis, of, five, 'TF']), verbo([target]), complemento(['genes,', our, data, provide, a, comprehensive, analysis, of, transcriptional, networks, that, regulate, 'TS', cell, 'self-renewal'])]). relacion([sujeto(['Although', allogeneic, bone, marrow, transplantation]), verbo([has]), complemento([been, shown, to, prevent, autoimmune, diabetes, in, heavily, irradiated, nonobese, diabetic, '(', 'NOD)', 'mice,', a, similar, procedure, is, not, suitable, for, the, treatment, of, patients, with, type, 1, diabetes, because, of, associated, severe, side, effects])]). relacion([sujeto(['Transfusion', of, allogeneic, 'NBB', but, not, adult, blood]), verbo([prevented]), complemento([diabetes, incidence, in, a, majority, of, treated, mice, for, a, prolonged, period, of, time])]). relacion([sujeto(['This', was, accompanied, by, the]), verbo([release]), complemento([of, insulin, in, response, to, a, challenge, with, glucose])]). relacion([sujeto(['Although', 'NBB', transfusion]), verbo([induced]), complemento([a, low, level, of, hematopoietic, 'microchimerism,', it, did, not, strictly, correlate, with, amelioration, of, diabetes])]). relacion([sujeto(['These', data, indicate, that, allogeneic, 'NBB', transfusion, can]), verbo([prevent]), complemento([diabetes, in, 'NOD', mice, associated, with, modulation, of, selected, cytokine, genes, implicated, in, diabetes, manifestation])]). relacion([sujeto(['The', data, presented, in, this, study]), verbo([provide]), complemento([the, proof, of, principle, for, the, utility, of, allogeneic, umbilical, cord, blood, transfusion, to, treat, patients, with, autoimmune, diabetes])]). relacion([sujeto(['We']), verbo([have]), complemento([known, since, 1991, how, to, induce, naive, 'CD4', 'T', cells, to, differentiate, in, vitro, into, 'Th2', cells, 'and,', over, the, ensuing, 'years,', a, comprehensive, picture, of, the, molecules, involved, in, this, important, process, has, emerged])]). relacion([sujeto(['GATA3', and, 'STAT5', are, both, essential, for, in, vitro, 'differentiation,']), verbo([stimulating]), complemento([naive, cells, through, a, process, involving, 'induction,', which, is, 'T-cell', receptor, '(', 'TCR)', dependent, but, interleukin, '(', 'IL)-4', 'independent,', and, 'commitment,', which, is, 'IL-4', dependent])]). relacion([sujeto(['GATA3', and, probably, 'STAT5', are]), verbo([required]), complemento([in, vivo, 'but,', at, least, for, certain, helminth, 'infections,', the, 'IL-4/IL-4Ra/STAT6', pathway, is, dispensable])]). relacion([sujeto(['The', role, of, thymic, stromal, lymphopoietin, and, of, low, 'TCR', signal, strength, and, the, participation, of, basophils, in, establishing, a, 'Th2-baising', in, vivo, environment]), verbo([have]), complemento([achieved, considerable, attention])]). relacion([sujeto(['Almost', all, neuroblastoma, tumors]), verbo([express]), complemento([excess, levels, of, 'Cyclin', 'D1', '(', 'CCND1)', compared, to, normal, tissues, and, other, tumor, types])]). relacion([sujeto(['Only', a, small, percentage, of, these, neuroblastoma, tumors]), verbo([have]), complemento(['high-level', amplification, of, the, 'Cyclin', 'D1', gene])]). relacion([sujeto(['The', other, neuroblastoma, tumors]), verbo([have]), complemento([equally, high, 'Cyclin', 'D1', expression, without, amplification])]). relacion([sujeto(['Silencing', of, 'Cyclin', 'D1', expression, was, previously]), verbo([found]), complemento([to, trigger, differentiation, of, neuroblastoma, cells])]). relacion([sujeto(['The']), verbo([cause]), complemento([for, the, 'Cyclin', 'D1', overexpression, is, unknown])]). relacion([sujeto(['We', identified, a, highly]), verbo([conserved]), complemento(['GATA3', binding, site, 27, bp, upstream, of, the, 'Cyclin', 'D1', transcriptional, start])]). relacion([sujeto(['Chromatin', immune, precipitation, confirmed]), verbo([binding]), complemento([of, 'GATA3', to, the, 'Cyclin', 'D1', promoter])]). relacion([sujeto(['Overexpression', of, 'GATA3']), verbo([induced]), complemento(['Cyclin', 'D1', promoter, 'activity,', which, decreased, after, 'site-directed', mutagenesis, of, the, 'GATA3', binding, site, in, the, 'Cyclin', 'D1', promoter])]). relacion([sujeto(['Moreover,', 'GATA3', silencing]), verbo([caused]), complemento([differentiation, that, was, similar, to, that, caused, by, 'Cyclin', 'D1', inhibition])]). relacion([sujeto(['These']), verbo([finding]), complemento([implicate, 'GATA3', in, 'Cyclin', 'D1', overexpression, in, neuroblastoma])]). relacion([sujeto([mRNA, expression, of, 17, genes, was, determined, by, means, of, quantitative, 'real-time', 'PCR', in, term, placenta, of, 36, families]), verbo([participating]), complemento([in, the, 'ALADDIN', study, '(', 'Assessment', of, 'Lifestyle', and, 'Allergic', 'Disease', 'During', 'Infancy)'])]). relacion([sujeto(['Significant', differences, in, mRNA, expression, levels, were, detected, at, the, foetal, side, of, the, 'placenta,', where, 'CD14', was]), verbo([expressed]), complemento([at, higher, levels, in, placentas, from, families, living, on, a, farm, compared, to, not, living, on, a, 'farm,', and, 'IL-12(p40)', was, expressed, at, lower, levels, when, the, father, was, sensitized, compared, to, nonsensitized])]). relacion([sujeto(['At', the, maternal, side, of, the, 'placenta,', higher, expression, of, 'STAT4', and, lower, expression, of, 'GATA3', were, detected, in, families, with, sensitized, compared, to, nonsensitized, 'mothers,', and, 'IL-12(p40)', was, lower]), verbo([expressed]), complemento([when, the, families, were, living, on, a, farm, compared, to, not, living, on, a, farm])]). relacion([sujeto(['Ovarian/primary', peritoneal, carcinoma, and, breast, carcinoma, are, the, gynaecological, cancers, that, most, frequently]), verbo([involve]), complemento([the, serosal, cavities])]). relacion([sujeto(['Differentially']), verbo([expressed]), complemento([candidate, genes, were, validated, using, quantitative, 'real-time', 'PCR', and, immunohistochemistry])]). relacion([sujeto(['We', identified, 288, unique, probes, that, were, significantly, differentially]), verbo([expressed]), complemento([in, the, two, cancers, by, greater, than, 3.5, -, 'fold,', of, which, 81, and, 207, were, overexpressed, in, breast, and, 'ovarian/peritoneal', 'carcinoma,', respectively])]). relacion([sujeto(['SAM', analysis, identified, 1078, differentially]), verbo([expressed]), complemento([probes, with, false, discovery, rate, less, than, 0.05])]). relacion([sujeto(['Expression', profiling, distinguishes, 'ovarian/peritoneal', carcinoma, from, breast, carcinoma, and, identifies, genes, that, are, differentially]), verbo([expressed]), complemento([in, these, two, tumour, types])]). relacion([sujeto(['The', molecular, signatures, unique, to, these, cancers, may, facilitate, their, differential, diagnosis, and, may]), verbo([provide]), complemento([a, molecular, basis, for, therapeutic, target, discovery])]). relacion([sujeto(['Estrogen', receptor, '(', 'ER)alpha', is, a, critical]), verbo([target]), complemento([of, therapeutic, strategies, to, control, the, proliferation, of, 'hormone-dependent', breast, cancers])]). relacion([sujeto(['Preferred', clinical, options]), verbo([have]), complemento([significant, adverse, side, effects, that, can, lead, to, treatment, resistance, due, to, the, persistence, of, active, estrogen, receptors])]). relacion([sujeto(['We']), verbo([have]), complemento([established, the, cellular, mechanism, by, which, 'indole-3-carbinol', '(', 'I3C),', a, promising, anticancer, phytochemical, from, 'Brassica', 'vegetables,', ablates, 'ERalpha', 'expression,', and, we, have, uncovered, a, critical, role, for, the, 'GATA3', transcription, factor, in, this, 'indole-regulated', cascade])]). relacion([sujeto(['I3C']), verbo([inhibits]), complemento([endogenous, binding, of, 'ERalpha', with, the, 3, '\'', -, enhancer, region, of, 'GATA3', and, disrupts, endogenous, 'GATA3', interactions, with, the, 'ERalpha', 'promoter,', leading, to, a, loss, of, 'GATA3', and, 'ERalpha', expression])]). relacion([sujeto(['Ectopic', expression, of, 'GATA3']), verbo([has]), complemento([no, effect, on, 'I3C-induced', 'ERalpha', protein, degradation, but, does, prevent, 'I3C', inhibition, of, 'ERalpha', promoter, 'activity,', demonstrating, the, importance, of, 'GATA3', in, this, 'I3C-triggered', cascade])]). relacion([sujeto(['Our', preclinical, results, implicate, 'I3C', as, a, novel, anticancer, agent, in, human, cancers, that, coexpress, 'ERalpha,', 'GATA3,', and, 'AhR,', a, combination]), verbo([found]), complemento([in, a, large, percentage, of, breast, cancers, but, not, in, other, critical, 'ERalpha', target, tissues, essential, to, patient, health])]). relacion([sujeto(['Immunosuppression', following, severe, sepsis, remains, a, significant, human, health, 'concern,', as, 'long-term', morbidity, and, mortality, rates, of, patients, who]), verbo([have]), complemento([recovered, from, 'life-threatening', septic, shock, remain, poor])]). relacion([sujeto(['Additionally,', 'CD4(+)CD62L(+)', 'T', cells, from, 'CLP', mice, exhibit, dysregulated, cytokine, production, after, in, vitro, skewing, with, exogenous, 'cytokines,', indicating, a]), verbo([decreased]), complemento([capability, of, these, cells, to, commit, to, either, the, 'T(H)1', or, 'T(H)2', lineage])]). relacion([sujeto(['These', results]), verbo([provide]), complemento([evidence, that, 'CD4(+)', 'T-cell', subsets, from, 'post-septic', mice, exhibit, defects, in, activation, and, effector, 'function,', possibly, due, to, chromatin, remodeling, proximal, to, genes, involved, in, cytokine, production, or, gene, transcription])]). relacion([sujeto(['In', 'vertebrates,', the]), verbo([conserved]), complemento(['Wnt', signalling, cascade, promotes, the, stabilization, and, nuclear, accumulation, of, 'beta-catenin,', which, then, associates, with, the, lymphoid, enhancer, 'factor/T', cell, factor, proteins, '(', 'LEF/TCFs)', to, activate, target, genes])]). relacion([sujeto(['Here', we, show, that, special, 'AT-rich']), verbo([binding]), complemento([protein, 1, '(', 'SATB1),', the, 'T', 'lineage-enriched', chromatin, organizer, and, global, 'regulator,', interacts, with, 'beta-catenin', and, recruits, it, to, 'SATB1\'s', genomic, binding, sites])]). relacion([sujeto(['GATA-3', is, a, 'T', helper, type, 2, '(', 'T(H)2)', specific, transcription, factor, that]), verbo([regulates]), complemento([production, of, 'T(H)2', cytokines, and, functions, as, 'T(H)2', lineage, determinant])]). relacion([sujeto(['SATB1', positively]), verbo([regulated]), complemento(['GATA-3', and, 'siRNA-mediated', knockdown, of, 'SATB1', downregulated, 'GATA-3', expression, in, differentiating, human, 'CD4(+)', 'T', 'cells,', suggesting, that, 'SATB1', influences, 'T(H)2', lineage, commitment, by, reprogramming, gene, expression])]). relacion([sujeto(['Furthermore,', chromatin, immunoprecipitation, analysis, revealed, that, 'SATB1']), verbo([recruits]), complemento(['beta-catenin', and, p300, acetyltransferase, on, 'GATA-3', promoter, in, differentiating, 'T(H)2', cells, in, a, 'Wnt-dependent', manner])]). relacion([sujeto(['The', 'SATB1:beta-catenin', complex]), verbo([activates]), complemento([a, number, of, 'SATB1', regulated, 'genes,', and, hence, this, study, has, potential, to, find, novel, 'Wnt', responsive, genes])]). relacion([sujeto(['These', results, demonstrate, that, 'SATB1', orchestrates, 'T(H)2', lineage, commitment, by]), verbo([mediating]), complemento(['Wnt/beta-catenin', signalling])]). relacion([sujeto(['This']), verbo([report]), complemento([identifies, a, new, global, transcription, factor, involved, in, 'beta-catenin', signalling, that, may, play, a, major, role, in, dictating, the, functional, outcomes, of, this, signalling, pathway, during, 'development,', 'differentiation,', and, tumorigenesis])]). relacion([sujeto(['Prenatal', exposures, to, immunogenic, 'stimuli,', such, as, bacterial, 'LPS,']), verbo([have]), complemento([shown, to, influence, the, neonatal, immune, system, and, lung, function])]). relacion([sujeto(['However,', no, detailed, analysis, of, the, immunomodulatory, effects, of, 'LPS', on, postnatal, 'T', helper, cell, differentiation]), verbo([has]), complemento([been, performed])]). relacion([sujeto(['Prenatal', 'LPS', exposure]), verbo([induced]), complemento([a, 'T', helper, 1, '(', 'T(H)1)', immune, milieu, in, the, offspring, of, rats, '[', i])]). relacion([sujeto([',']), verbo([increased]), complemento(['T-bet', and, 'T(H)1', cytokine, expression, while, expression, of, 'T(H)2-associated', transcription, factors, '(', 'GATA3', and, 'STAT6)', and, cytokines, was, 'decreased]'])]). relacion([sujeto(['Prenatal', 'LPS', exposure, did, not]), verbo([trigger]), complemento(['T(H)17', cell, differentiation, in, the, offspring])]). relacion([sujeto(['Thus,', in, utero, exposure, to, endotoxin]), verbo([promotes]), complemento([a, 'T(H)1', immune, 'environment,', which, suppresses, the, development, of, allergic, airway, disease, later, in, life])]). relacion([sujeto(['After', 2, -, 3, 'weeks,', colony, formation, was]), verbo([found]), complemento([in, 0, -, 4, wells, of, each, plate])]). relacion([sujeto(['Type', 'I', colony, cells, were, interpreted, as, composed, by, 'macrophage-lineage', 'cells,', since, they]), verbo([expressed]), complemento([a, specific, macrophage, 'marker,', 'M-CSFR/csf1r', 'gene,', and, most, of, them, phagocytosed, latex, particles])]). relacion([sujeto(['Type', 'II', colony, cells, were, interpreted, as, composed, by, 'T', lineage, 'cells,', since, they]), verbo([expressed]), complemento([several, 'T', cell, marker, genes, including, 'gata3,', lck, and, 'TCRbeta,', but, did, not, engulf, latex, particles])]). relacion([sujeto(['They']), verbo([expressed]), complemento([not, only, the, 'M-CSFR', gene, but, also, a, 'T', cell, marker, 'gene,', 'gata3,', but, not, other, 'T', cell, 'markers,', such, as, lck, and, 'TCRbeta'])]). relacion([sujeto(['We']), verbo([report]), complemento([herein, that, 'Aurora-A', transcription, is, positively, regulated, by, 'GATA-3', in, response, to, estrogen, in, estrogen, receptor, α, '(', 'ERα)-positive', cells])]). relacion([sujeto(['Transient', expression, of, 'aurora-A', promoter, deletion, mutants, in, luciferase, constructs, identified, a, 'GATA']), verbo([binding]), complemento([sequence, motif, as, a, functional, regulatory, element, in, 'ERα-positive', breast, cancer, cells])]). relacion([sujeto(['Electrophoretic', mobility, shift, assay, identified, the]), verbo([binding]), complemento([of, regulatory, proteins, to, the, 'GATA', element])]). relacion([sujeto(['Ectopic', expression, of, 'GATA-3', resulted, in, elevated, expression, of, 'Aurora-A', in, both, 'ERα-positive', and, negative, cells, while, 'siRNA-mediated', silencing]), verbo([led]), complemento([to, downregulation, of, endogenous, 'Aurora-A', in, 'ERα-positive', cells])]). relacion([sujeto(['Estrogen', treatment, of, 'ERα-positive', cells]), verbo([induced]), complemento([increased, 'Aurora-A', expression, with, enhanced, recruitment, of, 'GATA-3', to, the, 'aurora-A', promoter])]). relacion([sujeto(['Finally,', in, the, 'ACI', rat, model, of, 'estrogen-induced', breast, 'cancer,', known, to, be]), verbo([associated]), complemento([with, elevated, 'Aurora-A', 'expression,', we, observed, increased, expression, of, 'GATA-3', in, preinvasive, and, invasive, mammary, epithelial, cells, exposed, to, prolonged, estrogen, treatment, and, in, developing, breast, tumors])]). relacion([sujeto(['These', results, demonstrate, a, direct, positive, role, of, estrogen, in]), verbo([regulating]), complemento(['Aurora-A', expression, through, activation, of, the, 'ERα-GATA-3', signaling, cascade, and, suggest, that, this, pathway, may, be, critical, in, the, origin, of, 'estrogen-stimulated', sporadic, breast, cancer])]). relacion([sujeto(['The', aryl, hydrocarbon, receptor, '(', 'AhR)', is, part, of, a, signaling, system, that, is, mainly]), verbo([triggered]), complemento([by, xenobiotic, agents])]). relacion([sujeto(['Increasing', evidence]), verbo([suggests]), complemento([that, 'AhR', may, regulate, immunity, to, infections])]). relacion([sujeto(['Interestingly,', lower, numbers, of, cysts, were]), verbo([found]), complemento([in, their, brains])]). relacion([sujeto(['Increased', mortality, was]), verbo([associated]), complemento([with, reduced, expression, of, 'GATA-3,', 'IL-10,', and, 5, -, 'LOX', mRNA, in, spleen, cells, but, higher, expression, of, 'IFN-gamma', mRNA])]). relacion([sujeto(['These', findings]), verbo([suggest]), complemento([a, role, for, 'AhR', in, limiting, the, inflammatory, response, during, toxoplasmosis])]). relacion([sujeto(['Compared', with, the, untreated, 'controls,', 'TSLP', mRNA, expression, and, immunoreactivity, were, significantly]), verbo([increased]), complemento([in, the, corneal, and, conjunctival, epithelia, of, 'SRW-induced', 'AC', mice])]). relacion([sujeto(['CD11c(+)', and, 'OX40L(+)', immunoreactive, cells, largely, infiltrated, the, conjunctiva, with]), verbo([increased]), complemento([mRNA, levels, of, 'CD11c,', 'TSLPR,', and, 'OX40L', detected, in, the, corneal, 'epithelium,', 'conjunctiva,', and, cervical, lymph, nodes])]). relacion([sujeto(['CD4(+)', 'Th2', cell, infiltration, was, evidenced, by]), verbo([increased]), complemento([levels, of, mRNA, and, immunoreactivity, of, 'CD4,', 'IL-4,', 'IL-5,', and, 'IL-13', in, the, ocular, 'surface,', mainly, in, the, 'conjunctiva,', accompanied, by, increased, expression, of, 'OX40,', 'STAT6,', and, 'GATA3,', in, 'AC', mice])]). relacion([sujeto(['The', maturation, of, immature, 'DCs', was, observed, with, the, use, of, 'TSLP', containing, conditioned, media, from, corneal, epithelial, cultures, exposed, to, 'polyI:C,', which]), verbo([stimulates]), complemento(['TSLP', production])]). relacion([sujeto(['This', study]), verbo([provides]), complemento([new, findings, regarding, the, role, of, local, mucosal, epithelial, cells, in, the, initiation, of, ocular, allergic, inflammation, by, producing, a, novel, proallergic, 'cytokine,', 'TSLP,', which, activates, dendritic, cells, to, prime, 'Th2', differentiation, and, allergic, inflammation, through, the, 'TSLP-TSLPR', and, 'OX40L-OX40', signaling, pathway])]). relacion([sujeto(['The', 'Ca(2+)', dependent, transcription, factor, family, known, as]), verbo([nuclear]), complemento([factor, of, activated, 'T', cells, '(', 'NFAT)', has, been, shown, to, be, important, in, 'T-cell', immune, responses])]). relacion([sujeto(['Because', 'NFAT', proteins]), verbo([have]), complemento([a, weak, 'DNA-binding', 'capacity,', they, cooperate, with, other, transcription, factors, at, composite, sites, within, the, promoters, of, target, genes])]). relacion([sujeto(['Subsequently,', the, integration, of, these, complex, intracellular, signal, transduction, cascades, is, considered, to, critically, determine, the, crosstalk, between, the, 'T-cell', receptor, and, receptors, that, are]), verbo([activated]), complemento([by, both, the, adaptive, and, innate, immune, systems, to, determine, pathways, of, 'T', helper, cell, differentiation, and, function])]). relacion([sujeto(['Our', findings]), verbo([suggest]), complemento([that, in, breast, 'cancer,', the, frequency, of, tumor, cells, positive, for, stem, 'cell-like', and, more, differentiated, cell, markers, varies, according, to, tumor, subtype, and, histologic, stage])]). relacion([sujeto(['The', normal, counterparts, of, peripheral, 'T-cell', 'lymphoma,', not, otherwise, specified, '(', 'PTCL-NOS)']), verbo([have]), complemento([not, been, accurately, identified])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([the, postulated, normal, counterparts, of, 'PTCL-NOS', identified, in, 9, of, the, 10, cases, consist, of, 'T(H)1,', 'T(H)2,', 'TCM,', and, 'TFH'])]). relacion([sujeto(['S-nitrosoglutathione', '(', 'GSNO)', is, a, physiological, nitric, oxide, molecule, which]), verbo([regulates]), complemento([biological, activities, of, target, proteins, via, 's-nitrosylation', leading, to, attenuation, of, chronic, inflammation])]). relacion([sujeto(['Oral', administration, of, 'GSNO', '(', 0.5, or, 1.0, 'mg/kg)', reduced, disease, progression, in, chronic, models, '(', 'SJL', and, 'C57BL/6)', of, 'EAE']), verbo([induced]), complemento([with, 'PLP((139-151))', or, 'MOG((35-55))', 'peptides,', respectively])]). relacion([sujeto(['In', vitro, studies, showed, that, the, phosphorylation, of, 'STAT3', and, expression, of, 'ROR', 'gamma,', key, regulators, of, 'IL17', 'signaling,', were, reduced, while, phosphorylation, of, 'STAT4', or, 'STAT6', and, expression, of, 'T-bet', or, 'GATA3', remained, 'unaffected,']), verbo([suggesting]), complemento([that, 'GSNO', preferentially, targets, 'Th17', cells])]). relacion([sujeto(['Collectively,', 'GSNO', attenuated, 'EAE', via, modulation, of, 'Th17', cells, and, its, effects, are, independent, of, 'Th1', or, 'Th2', cells, 'functions,', indicating, that, it, may]), verbo([have]), complemento([therapeutic, potential, for, 'Th17-mediated', autoimmune, diseases])]). relacion([sujeto(['We', recently]), verbo([reported]), complemento([that, 'IL-4+TGF-beta', directs, mouse, 'CD4(+)CD25(-)CD62L(+)', 'T', cells, to, commit, to, inflammatory, 'IL-9', producing, 'CD4(+)', 'T', cells])]). relacion([sujeto(['Here', we, show, that, human, inducible, regulatory, 'T', cells, '(', 'iTregs)', also]), verbo([express]), complemento(['IL-9'])]). relacion([sujeto(['IL-4+TGF-beta']), verbo([induced]), complemento([higher, levels, of, 'IL-9', expression, in, plate, 'bound-anti-CD3', mAb, '(', 'pbCD3)/soluble-anti-CD28', mAb, '(', 'sCD28)', activated, human, resting, memory, 'CD4(+)CD25(-)CD45RO(+)', 'T', cells, as, compared, to, naïve, 'CD4(+)CD25(-)CD45RA(+)', 'T', cells])]). relacion([sujeto(['In', 'addition,', as, compared, to, 'pbCD3/sCD28', plus, 'TGF-beta', 'stimulation,', 'IL-4+TGF-beta']), verbo([stimulated]), complemento([memory, 'CD4(+)CD25(-)CD45RO(+)', 'T', cells, expressed, reduced, 'FOXP3', protein])]). relacion([sujeto(['As', analyzed, by, 'pre-amplification', boosted, 'single-cell', 'real-time', 'PCR,', human, 'CD4(+)IL-9(+)', 'T', cells]), verbo([expressed]), complemento(['GATA3', and, 'RORC,', but, not, 'IL-10,', 'IL-13,', 'IFNgamma', or, 'IL-17A/F'])]). relacion([sujeto(['Attempts', to, optimize, 'IL-9', production, by, 'pbCD3/sCD28', and, 'IL-4+TGF-beta']), verbo([stimulated]), complemento([resting, memory, 'CD4(+)', 'T', cells, demonstrated, that, the, addition, of, 'IL-1beta,', 'IL-12,', and, 'IL-21', further, enhance, 'IL-9', production])]). relacion([sujeto(['Taken', together, these, data, show, both, the, differences, and, similarities, between, mouse, and, human, 'CD4(+)IL9(+)', 'T', cells, and, reaffirm, the, powerful, influence, of, inflammatory, cytokines, to, shape, the, response, of]), verbo([activated]), complemento(['CD4(+)', 'T', cells, to, antigen])]). relacion([sujeto(['The', mouse, blastocyst, and, stem, cells, derived, from, its, tissue, lineages]), verbo([provide]), complemento([a, unique, genetic, system, for, examining, the, establishment, and, loss, of, pluripotency])]). relacion([sujeto(['The', transcription, factor, 'Cdx2', plays, a, central, role, by, repressing, pluripotency, 'genes,', such, as, 'Oct4,', and]), verbo([promoting]), complemento([extraembryonic, trophoblast, fate, at, the, blastocyst, stage])]). relacion([sujeto(['However,', genetic, evidence]), verbo([has]), complemento([suggested, that, 'Cdx2', does, not, work, alone, in, the, trophoblast, lineage])]). relacion([sujeto(['We']), verbo([have]), complemento([used, bioinformatic, and, functional, genomic, strategies, to, identify, the, transcription, factor, 'Gata3', as, a, trophoblast, factor])]). relacion([sujeto(['We', show, 'Gata3', to, be, capable, of]), verbo([inducing]), complemento([trophoblast, fate, in, embryonic, stem, cells, and, driving, trophoblast, differentiation, in, trophoblast, stem, cells])]). relacion([sujeto(['In', 'addition,', 'Cdx2', is, not]), verbo([required]), complemento([for, 'Gata3-induced', expression, of, a, subset, of, trophoblast, genes, in, embryonic, stem, cells])]). relacion([sujeto(['These', observations]), verbo([suggest]), complemento([that, 'Gata3', and, 'Cdx2', can, act, in, parallel, pathways, downstream, of, 'Tead4', to, induce, the, expression, of, common, and, independent, targets, in, the, trophoblast, 'lineage,', whereas, 'Oct4', is, required, for, continued, repression, of, trophoblast, fate, in, the, embryonic, lineage])]). relacion([sujeto(['Here', we, show, that, infection, with, 'Th1', 'cell-promoting', lymphocytic, choriomeningitis, virus, '(', 'LCMV)', reprogrammed, otherwise, stably, committed, 'GATA-3(+)', 'Th2', cells, to, adopt, a, 'GATA-3(+)T-bet(+)', and, 'interleukin-4(+)interferon-gamma(+)', &, 'quot;Th2+1"', phenotype, that, was]), verbo([maintained]), complemento([in, vivo, for, months])]). relacion([sujeto(['Th2', cell, reprogramming]), verbo([required]), complemento(['T', cell, receptor, 'stimulation,', concerted, type, 'I', and, type, 'II', interferon, and, 'interleukin-12', 'signals,', and, 'T-bet'])]). relacion([sujeto(['LCMV-triggered', 'T-bet', induction, in, adoptively, transferred, 'virus-specific', 'Th2', cells, was, crucial, to]), verbo([prevent]), complemento([viral, persistence, and, fatal, immunopathology])]). relacion([sujeto(['Stable', coexpression, of, 'GATA-3', and, 'T-bet']), verbo([provides]), complemento([a, molecular, concept, for, the, 'long-term', coexistence, of, 'Th2', and, 'Th1', cell, lineage, characteristics, in, single, memory, 'T', cells])]). relacion([sujeto(['RNAi', is, a, popular, method, of, controlling, gene, expression, and]), verbo([has]), complemento([potential, in, the, development, of, drugs, for, several, 'diseases,', such, as, various, types, of, cancer, and, viral, infections])]). relacion([sujeto(['Gene', therapy, for, asthma]), verbo([has]), complemento([already, been, developed, and, has, demonstrated, promising, results, in, animal, models])]). relacion([sujeto(['Recent', progress, in, delivering, siRNA, to, the, respiratory, system]), verbo([has]), complemento([also, improved, the, therapeutic, feasibility, of, 'RNAi', for, asthma])]). relacion([sujeto(['In', this, 'review,', the, 'mechanism,', as, well, as, the, general, strategies, and, problems]), verbo([associated]), complemento([with, the, application, of, 'RNAi', in, 'vivo,', are, 'discussed,', focusing, on, the, possibility, of, applying, 'RNAi', to, alleviate, airway, inflammation, in, allergic, asthma])]). relacion([sujeto(['Data', from, studies, with, siRNA, against, molecules]), verbo([involved]), complemento([in, allergic, responses, are, 'summarized,', and, the, potential, and, limitations, of, 'RNAi', as, a, novel, therapeutic, approach, are, discussed])]). relacion([sujeto(['Conventional', vaccines, to]), verbo([prevent]), complemento([the, pneumonia, caused, by, 'Rhodococcus', equi, have, not, been, successful])]). relacion([sujeto(['We']), verbo([have]), complemento([recently, demonstrated, that, immunization, with, 'Salmonella', enterica, 'Typhimurium', expressing, the, 'VapA', antigen, protects, mice, against, 'R'])]). relacion([sujeto(['We', now]), verbo([report]), complemento([that, oral, vaccination, of, mice, with, this, recombinant, strain, results, in, high, and, persistent, fecal, levels, of, 'antigen-specific', 'IgA,', and, specific, proliferation, of, the, spleen, cells, of, immunized, mice, in, response, to, the, in, vitro, stimulation, with, 'R'])]). relacion([sujeto(['Finally,', we, show, that, the, vaccination]), verbo([confers]), complemento([a, 'long-term', protection, against, 'R'])]). relacion([sujeto([enterica, 'Typhimurium']), verbo([expressing]), complemento(['VapA', induces, specific, and, 'long-lasting', humoral, and, cellular, responses, against, the, 'pathogen,', which, are, appropriately, regulated, and, allow, tissue, integrity, after, challenge])]). relacion([sujeto(['Estrogen', receptor, alpha, '(', 'ERalpha)-positive', breast, cancers, that, 'co-express', transcription, factors, 'GATA-3', and, 'FOXA1']), verbo([have]), complemento([a, favorable, prognosis])]). relacion([sujeto(['In', this, 'study,', we]), verbo([report]), complemento([that, insulin, increases, the, expression, of, 'T-bet', in, breast, cancer, 'cells,', which, correlates, with, reduced, expression, of, 'GATA-3,', 'FOXA1,', and, the, 'ERalpha:FOXA1:GATA-3', target, gene, 'GREB-1'])]). relacion([sujeto(['Chromatin', immunoprecipitation, assays, revealed, reduced, 'ERalpha']), verbo([binding]), complemento([to, 'GREB-1', enhancer, regions, in, 'MCF-7-T-bet', cells, and, in, 'insulin-treated', 'MCF-7', cells])]). relacion([sujeto(['ERalpha-positive', cells, with, intrinsic, tamoxifen, resistance, as, well, as, 'MCF-7', cells, with, acquired, tamoxifen, and, fulvestrant, resistance]), verbo([expressed]), complemento([elevated, levels, of, 'T-bet', 'and/or', reduced, levels, of, 'FOXA1', and, 'GATA-3'])]). relacion([sujeto(['Analysis', of, publicly, available, databases, revealed, 'ERalpha-positive/T-bet-positive', breast, cancers]), verbo([expressing]), complemento([lower, levels, of, 'FOXA1', '(', 'P', =, 0.0137, ')', and, 'GATA-3', '(', 'P', =, 0.0063, ')', compared, with, 'ERalpha-positive/T-bet-negative', breast, cancers])]). relacion([sujeto(['Thus,', 'T-bet', expression, in, primary, tumors, and, circulating, insulin, levels, may, serve, as, surrogate, biomarkers, to, identify, 'ERalpha-positive', breast, cancers, with, a, dysfunctional, hormonal, 'network,']), verbo([enhanced]), complemento([growth, factor, 'signaling,', and, resistance, to, hormonal, therapy])]). relacion([sujeto(['CD4', 'T', helper, 2, '(', 'Th2)', cells]), verbo([have]), complemento([critical, functions, in, immune, responses, against, extracellular, parasites, and, are, involved, in, asthma, and, other, allergic, diseases])]). relacion([sujeto(['In', this, 'review,', regulation, of, 'GATA3', expression, and, 'STAT5', activation, and, functions, of, these, two, transcription, factors, in]), verbo([inducing]), complemento([the, expression, of, 'Th2', 'cytokines,', cytokine, receptors, as, well, as, epigenetic, modification, at, 'Th2', cytokine, locus, are, summarized])]). relacion([sujeto(['We']), verbo([have]), complemento([characterized, the, promoter, methylation, profile, of, 82, genes, in, three, prostate, cancer, cell, lines, '(', 'LNCaP,', 'PC3,', and, 'DU145)', and, two, normal, prostate, cell, lines, '(', 'RWPE1', and, 'RWPE2)'])]). relacion([sujeto(['Methylation']), verbo([binding]), complemento(['protein-purified', methylated, 'DNA', was, hybridized, on, the, membrane, and, detected, by, the, chemiluminescence, method])]). relacion([sujeto(['In', 'addition,', promoter, methylation, was, detected, for, the, first, time, in]), verbo([target]), complemento([genes, such, as, 'RIOK3,', 'STAT5,', 'CASP8,', 'SRBC,', 'GAGE1,', and, 'NPAT'])]). relacion([sujeto(['The', 'Th2', cytokine, gene, locus]), verbo([has]), complemento([emerged, as, a, remarkable, example, of, coordinated, gene, 'expression,', the, regulation, of, which, seems, to, be, rooted, in, an, extensive, array, of, 'cis-regulatory', regions])]). relacion([sujeto(['Using', a, 'hypothesis-generating', computational, approach, that, integrated, multispecies, '(', n, =, 11, ')', sequence, comparisons, with, 'algorithm-based', transcription, factor, 'binding-site', 'predictions,', we, sought, to, identify, evolutionarily]), verbo([conserved]), complemento([noncoding, regions, '(', 'ECRs)', and, motifs, shared, among, 'them,', which, may, underlie, coregulation])]). relacion([sujeto(['Twenty-two', transcription, factor, families, were, predicted, to]), verbo([have]), complemento([binding, sites, in, at, least, two, 'Th2', 'ECRs'])]). relacion([sujeto(['Unexpectedly,', sites, for, 'ETS-domain', proteins, were, also, predicted, within, several, 'Th2', 'ECRs', and, the, majority, of, these, sites, were]), verbo([found]), complemento([to, support, 'Ets-1', binding, in, vitro, and, in, vivo])]). relacion([sujeto(['Of', 'note,', the, expression, of, all, three, 'Th2', cytokines, '(', 'IL-5,', -, 13, ',', and, -, 4, ')', was, significantly, and, selectively]), verbo([decreased]), complemento([in, 'Th2', cells, generated, from, 'Ets-1-deficient', mice])]). relacion([sujeto(['Collectively,', these, data]), verbo([suggest]), complemento([that, 'Ets-1', contributes, to, 'Th2', cytokine, gene, regulation, by, interacting, with, multiple, 'cis-regulatory', regions, throughout, the, 'Th2', locus])]). relacion([sujeto(['The', murine, model, of, asthma, was]), verbo([induced]), complemento([by, 'OVA'])]). relacion([sujeto(['The', treatment, with, baicalin, obviously]), verbo([decreased]), complemento([the, production, of, 'IL-4', and, 'IL-5', and, the, gene, expression, of, 'GATA-3,', 'STAT-6,', but, increased, the, production, of, 'IL-10'])]). relacion([sujeto(['Baicalin', may]), verbo([modulate]), complemento([the, 'Th1/Th2', balance, mainly, by, altering, the, gene, expressions, of, 'GATA-3', and, 'STAT-6', in, vivo, and, increasing, the, production, of, 'IL-10'])]). relacion([sujeto(['Because', mouse, embryonic, stem, cells, '(', 'mESCs)', do, not, contribute, to, the, formation, of, extraembryonic, placenta, when, they, are, injected, into, 'blastocysts,', it, is, believed, that, mESCs, do, not, differentiate, into, trophoblast, whereas, human, embryonic, stem, cells, '(', 'hESCs)', can]), verbo([express]), complemento([trophoblast, markers, when, exposed, to, bone, morphogenetic, protein, 4, '(', 'BMP4)', in, vitro])]). relacion([sujeto(['To', test, whether, mESCs]), verbo([have]), complemento([the, potential, to, differentiate, into, 'trophoblast,', we, assessed, the, effect, of, 'BMP4', on, mESCs, in, a, defined, monolayer, culture, condition])]). relacion([sujeto(['The', expression, of, 'trophoblast-specific', transcription, factors, such, as, 'Cdx2,', 'Dlx3,', 'Esx1,', 'Gata3,', 'Hand1,', 'Mash2,', and, 'Plx1', was, specifically, upregulated, in, the, 'BMP4-treated', differentiated, 'cells,', and, these, cells]), verbo([expressed]), complemento([trophoblast, markers])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, 'BMP4', treatment, in, defined, culture, conditions, enabled, mESCs, to, differentiate, into, trophoblast])]). relacion([sujeto(['This', differentiation, was]), verbo([inhibited]), complemento([by, serum, or, leukemia, inhibitory, 'factor,', which, are, generally, used, for, mESC, culture])]). relacion([sujeto(['Our', results, showed, that, 'BMP4']), verbo([activates]), complemento([the, 'Smad', pathway, in, mESCs, inducing, 'Cdx2', 'expression,', which, plays, a, crucial, role, in, trophoblast, 'differentiation,', through, the, binding, of, 'Smad', protein, to, the, 'Cdx2', genomic, enhancer, sequence])]). relacion([sujeto(['Patients', with, 'Wiskott-Aldrich', syndrome, '(', 'WAS)']), verbo([have]), complemento([numerous, immune, cell, 'deficiencies,', but, it, remains, unclear, how, abnormalities, in, individual, cell, types, contribute, to, the, pathologies, of, 'WAS'])]). relacion([sujeto(['In', 'T', 'cells,', the, 'WAS', protein, '(', 'WASp)']), verbo([regulates]), complemento([actin, polymerization, and, 'transcription,', and, plays, a, role, in, the, dynamics, of, the, immunologic, synapse])]). relacion([sujeto(['WAS(-/-)', 'CD4(+)', 'T', cells]), verbo([mediated]), complemento([protective, 'T-helper', 1, '(', 'Th1)', responses, to, 'Leishmania', major, in, 'vivo,', but, were, unable, to, support, 'Th2', immunity, to, 'Nippostrongylus', brasiliensis, or, 'L', major])]). relacion([sujeto(['Mechanistically,', 'WASp', was, not]), verbo([required]), complemento([for, 'Th2', programming, but, was, required, for, 'Th2', effector, function])]). relacion([sujeto(['Because', the, role, of, 'pro-inflammatory', cytokine, in, the, acute, phase, of, pediatric, 'IBD']), verbo([has]), complemento([not, been, well, 'investigated,', the, serum, levels, of, 'pro-inflammatory', cytokines, and, the, expression, of, 'Th1', and, 'Th2', signaling, molecules, in, mucosa, from, the, acute, phase, of, pediatric, 'IBD', were, examined])]). relacion([sujeto(['Expression', of, 'T-helper', cell, 1, '(', 'Th1)', '(', 'T-box']), verbo([expressed]), complemento([in, 'T', 'cells:', 'T-bet', and, signal, transducer, and, activator, of, 'transcription-4:', 'STAT-4)', and, 'Th2', '(', 'GATA-3', and, 'STAT-6)', signaling, molecules, was, examined, on, 'real-time', polymerase, chain, reaction, using, mucosal, samples, from, eight, children, in, the, acute, phase, of, 'UC,', eight, with, 'CD', and, eight, controls])]). relacion([sujeto(['The', mucosal, expression, of, 'GATA-3', and, 'STAT-4', was, significantly]), verbo([enhanced]), complemento([in, the, acute, phase, of, pediatric, 'UC', compared, with, normal, mucosa])]). relacion([sujeto(['IL-4', and, its, signaling, molecule, 'GATA-3,', as, well, as, the, 'Th1', signaling, molecule, 'STAT-4,', are]), verbo([involved]), complemento([in, the, pathogenesis, of, acute, phase, of, pediatric, 'UC'])]). relacion([sujeto(['Based', on, observations, that, mutations, of, 'GATA-3', are, responsible, for, the, 'HDR-syndrome', '(', 'hypoparathyroidism,', 'deafness,', renal, 'defects)', and, that, 'GATA-transcription', factors]), verbo([have]), complemento([an, important, role, to, play, in, inner, ear, 'development,', we, hypothesized, that, these, transcription, factors, may, be, involved, in, regulatory, changes, of, prestin, transcription])]). relacion([sujeto(['(', 'ii)', 'The', prestin, expression]), verbo([increases]), complemento([between, postnatal, day, two, and, postnatal, day, eight, by, a, factor, of, about, four, in, the, apical, and, middle, segments, and, by, a, factor, of, two, in, the, basal, part])]). relacion([sujeto(['These', observations]), verbo([suggest]), complemento([a, regulatory, role, played, by, the, 'Gata-3,-2', transcription, factors, in, prestin, expression])]). relacion([sujeto(['This', study, investigated, the, association, of, mRNA, levels, of, the, transcription, factors, 'T-box']), verbo([expressed]), complemento([in, 'T', cells, and, 'GATA-binding', protein, 3, with, the, development, of, 'T(h)1/T(h)2-directed', immune, responses])]). relacion([sujeto(['We', observed, a, nonsignificant]), verbo([increase]), complemento([in, 'T-bet', expression, following, allografting, at, days, 3, and, 5, but, there, was, a, significant, reduction, in, 'GATA-3', expression, on, day, 5, compared, with, controls])]). relacion([sujeto(['The', ratio, of, 'T-bet', to, 'GATA-3', expression, showed, a, trend, to]), verbo([increase]), complemento([at, day, 3, following, allografting, reaching, significance, at, 5, days])]). relacion([sujeto(['These', changes, were]), verbo([associated]), complemento([with, a, significant, increase, in, the, expression, of, 'IL-2', over, 'IL-4', on, days, 3, and, 5])]). relacion([sujeto(['This', study]), verbo([suggests]), complemento([that, 'T(h)1', responses, play, a, major, role, during, 'AR', in, the, rat, 'lung,', and, that, this, differentiation, can, be, monitored, by, measuring, mRNA, levels, of, 'T-bet', and, 'GATA-3'])]). relacion([sujeto(['Leptin', was]), verbo([found]), complemento([to, be, necessary, in, 'T', helper, 1, '(', 'Th1)-dependent', inflammatory, 'processes,', whereas, effects, on, 'Th2', cells, are, rarely, understood])]). relacion([sujeto(['The', induction, of, 'cytokine-producing', 'Th1', or, 'Th2', cells, from, naive, 'CD4(+)', 'T', cells, under, polarizing, conditions, in, vitro, was, generally]), verbo([decreased]), complemento([in, cells, from, 'leptin-deficient', 'ob/ob', mice, compared, with, 'wild-type', mice])]). relacion([sujeto(['A', possible, explanation, for, the, protection, of, 'ob/ob', mice, in, 'Th1-', as, well, as, in, 'Th2-dependent', inflammation, is]), verbo([provided]), complemento([by, a, decreased, expression, of, the, key, transcription, factors, for, 'Th1', and, 'Th2', 'polarization,', 'T-bet', and, 'GATA-3,', in, naive, 'ob/ob', 'T', cells])]). relacion([sujeto(['Palmitoylation', is, a, key, 'post-translational', modification]), verbo([mediated]), complemento([by, a, family, of, 'DHHC-containing', palmitoyl, 'acyl-transferases', '(', 'PATs)'])]). relacion([sujeto(['Unlike', other, lipid, 'modifications,', palmitoylation, is, reversible, and, thus, often]), verbo([regulates]), complemento([dynamic, protein, interactions])]). relacion([sujeto(['We']), verbo([find]), complemento([that, the, mouse, hair, loss, 'mutant,', 'depilated,', '(', 'dep)', is, due, to, a, single, amino, acid, deletion, in, the, 'PAT,', 'Zdhhc21,', resulting, in, protein, mislocalization, and, loss, of, palmitoylation, activity])]). relacion([sujeto(['We', examined, expression, of, 'Zdhhc21', protein, in, skin, and]), verbo([find]), complemento([it, restricted, to, specific, hair, lineages])]). relacion([sujeto(['Loss', of, 'Zdhhc21', function, results, in, delayed, hair, shaft, 'differentiation,', at, the, site, of, expression, of, the, 'gene,', but, also]), verbo([leads]), complemento([to, hyperplasia, of, the, interfollicular, epidermis, '(', 'IFE)', and, sebaceous, 'glands,', distant, from, the, expression, site])]). relacion([sujeto(['The', specific, delay, in, follicle, differentiation, is]), verbo([associated]), complemento([with, attenuated, anagen, propagation, and, is, reflected, by, decreased, levels, of, 'Lef1,', nuclear, 'beta-catenin,', and, 'Foxn1', in, hair, shaft, progenitors])]). relacion([sujeto(['In', the, thickened, basal, compartment, of, mutant, 'IFE,', 'phospho-ERK', and, cell, proliferation, are, 'increased,']), verbo([suggesting]), complemento([increased, signaling, through, 'EGFR', or, 'integrin-related', 'receptors,', with, a, parallel, reduction, in, expression, of, the, key, differentiation, factor, 'Gata3'])]). relacion([sujeto(['We', show, that, the, 'Src-family', 'kinase,', 'Fyn,']), verbo([involved]), complemento([in, keratinocyte, 'differentiation,', is, a, direct, palmitoylation, target, of, 'Zdhhc21', and, is, mislocalized, in, mutant, follicles])]). relacion([sujeto(['This', study, is, the, first, to, demonstrate, a, key, role, for, palmitoylation, in]), verbo([regulating]), complemento([developmental, signals, in, mammalian, tissue, homeostasis])]). relacion([sujeto(['The', levels, of, plasma, 'IL-18', and, 'IL-18R', on, 'CD3(+)', lymphocytes, were, significantly]), verbo([increased]), complemento([in, active, phase, 'ITP', than, in, remission, phase, and, controls])]). relacion([sujeto(['We']), verbo([report]), complemento([on, a, 'Japanese', girl, with, 'HDR', '(', 'hypoparathyroidism,', sensorineural, 'deafness,', and, renal, 'dysplasia)', syndrome, who, developed, diabetes, mellitus, '(', 'DM)', at, three, years, of, age, '(', blood, glucose, 713, 'mg/dL,', 'HbA(1c)', 8.0, '%', ')', in, the, absence, of, 'anti-glutamic', acid, decarboxylase, autoantibodies])]). relacion([sujeto(['GATA3', expression, was, identified, by, 'PCR', amplification, for, human, pancreas, 'cDNA,', and, mouse, 'Gata3', was, weekly, but, unequivocally]), verbo([expressed]), complemento([in, pancreatic, beta, cells])]). relacion([sujeto(['The', 'results,', in, conjunction, with, the, previous, findings, indicating, the, critical, role, of, 'GATA3', in, lymphocyte, 'function,', 'GATA3', haploinsufficiency, may, affect, the, function, of, beta, cells, 'and/or', 'lymphocytes,']), verbo([leading]), complemento([to, the, development, of, 'DM', in, relatively, exceptional, patients, with, high, susceptibility, to, 'DM'])]). relacion([sujeto(['The', 'Oncotype', 'DX', assay, is, one, of, the, molecular, tests, that]), verbo([provide]), complemento([predictive, and, prognostic, information, to, breast, cancer, patients, with, estrogen, receptor, '(', 'ER)-positive', and, 'node-negative', disease])]). relacion([sujeto(['In', this, 'study,', we, show, that, in, an, 'allergen-induced', asthma, 'model,', mice, with, transgenic, overexpression, of, 'IL-23R', exhibited]), verbo([increased]), complemento([airway, infiltration, of, eosinophils, and, 'Th2', cytokine, 'production,', whereas, those, deficient, in, 'IL-23', displayed, reduced, airway, inflammation])]). relacion([sujeto(['In', 'vitro,', 'IL-23-IL-23R', signaling]), verbo([promoted]), complemento(['GATA-3', expression, and, enhanced, 'Th2', cytokine, expression])]). relacion([sujeto(['Therefore,', 'IL-23', signaling, may]), verbo([regulate]), complemento([allergic, asthma, through, modulation, of, 'Th2', cell, differentiation])]). relacion([sujeto(['The', transcription, factor, 'GATA-3', is]), verbo([required]), complemento([for, the, development, of, 'T', lymphocytes, at, multiple, late, differentiation, steps, as, well, as, for, the, development, of, thymic, natural, killer, cells])]). relacion([sujeto(['However,', a, role, for, 'GATA-3', before, the, 'double-negative', '(', 'DN)', 3, stage, of, 'T', cell, development]), verbo([has]), complemento([to, date, been, obscured, both, by, the, developmental, heterogeneity, of, 'DN1', thymocytes, and, the, paucity, of, 'ETPs'])]). relacion([sujeto(['We']), verbo([provide]), complemento([multiple, lines, of, in, vivo, evidence, through, the, analysis, of, 'T', cell, development, in, 'Gata3', hypomorphic, mutant, 'embryos,', in, irradiated, mice, reconstituted, with, 'Gata3', mutant, hematopoietic, 'cells,', and, in, mice, conditionally, ablated, for, the, 'Gata3', gene, to, show, that, 'GATA-3', is, required, for, 'ETP', generation])]). relacion([sujeto(['We', further, show, that, 'Gata3']), verbo([loss]), complemento([does, not, affect, hematopoietic, stem, cells, or, multipotent, hematopoietic, progenitors])]). relacion([sujeto(['Finally,', we, demonstrate, that, 'Gata3', mutant, lymphoid, progenitors, exhibit, neither]), verbo([increased]), complemento([apoptosis, nor, diminished, 'cell-cycle', progression])]). relacion([sujeto(['Thus,', 'GATA-3', is]), verbo([required]), complemento([for, the, 'cell-autonomous', development, of, the, earliest, characterized, thymic, 'T', cell, progenitors])]). relacion([sujeto(['Recently,', it, was]), verbo([reported]), complemento([that, the, expression, of, 'Runt-related', transcription, factor, 3, '(', 'Runx3)', is, 'up-regulated', in, 'CD4(+)', helper, 'T', cells, during, 'Th1', cell, 'differentiation,', and, that, 'Runx3', functions, in, a, positive, 'feed-forward', manner, with, the, 'T-box', family, transcription, 'factor,', 'T-bet,', which, is, a, master, regulator, of, 'Th1', cell, differentiation])]). relacion([sujeto(['The', relative, expression, levels, of, 'IFN-gamma', and, 'IL-4', are, also]), verbo([regulated]), complemento([by, the, 'Th2-associated', transcription, 'factor,', 'GATA3'])]). relacion([sujeto(['Here,', we, demonstrate, that, 'Runx3', was]), verbo([induced]), complemento([in, 'Th2', as, well, as, 'Th1', cells, and, that, 'Runx3', interacted, with, 'GATA3', and, attenuated, 'GATA3', transcriptional, activity])]). relacion([sujeto(['Our', results]), verbo([suggest]), complemento([that, the, balance, of, 'Runx3', and, 'GATA3', is, one, factor, that, influences, the, manifestation, of, 'CD4(+)', cells, as, the, 'Th1', or, 'Th2', phenotypes])]). relacion([sujeto(['Haploinsufficiency', for, the, transcription, factor, 'GATA3']), verbo([leads]), complemento([to, hearing, loss, in, humans])]). relacion([sujeto(['It', is]), verbo([expressed]), complemento([throughout, the, auditory, sensory, epithelium, '(', 'SE)'])]). relacion([sujeto(['The', striola, is]), verbo([conserved]), complemento([in, all, 'amniotes,', its, function, is, 'unknown,', and, 'GATA3', is, the, only, known, marker, of, the, reversal, zone])]). relacion([sujeto(['To', identify, downstream]), verbo([targets]), complemento([of, 'GATA3', that, might, point, to, striolar, 'function,', we, measured, gene, expression, differences, between, striolar, and, 'extra-striolar', 'SE'])]). relacion([sujeto(['Two', of, these, '(', 'LMO4', and, 'MBNL2)', were, shown, to, be, direct]), verbo([targets]), complemento([of, 'GATA3', by, 'ChIP'])]). relacion([sujeto(['Our', results]), verbo([suggest]), complemento([that, 'GATA3', impacts, 'WNT', signaling, in, this, region, of, the, sensory, macula])]). relacion([sujeto(['Rejection', of, transplanted, liver, occurs, when, the, host, generates, 'alloantigen-reactive', 'T', 'cells,', and, 'CD4(+)', 'T-cell', 'subsets,', including, 'Th1,', 'Th2,', 'T17', and, 'iTreg,', could, be]), verbo([involved]), complemento([in, changing, the, dynamics, of, graft, rejection, onset])]). relacion([sujeto(['In', recipient, 'spleens,', the, 'T-bet(+)', and, 'RORgammat(+)', cells, were]), verbo([increased]), complemento([more, significantly, in, the, mild, acute, rejection, '(', 'AR)', group, than, in, the, control, group, '(', 'P=0'])]). relacion([sujeto([9, ',', 'respectively),', while, both, cell, types, were]), verbo([decreased]), complemento([in, the, moderate, 'AR', group])]). relacion([sujeto(['Compared', with, the, control, 'group,', the, 'RORgammat(+)', cells, did, not, differ, significantly, in, the, severe, 'AR', 'group,', while, the, 'T-bet(+)', cells, were, significantly]), verbo([decreased]), complemento(['(', 'P=0'])]). relacion([sujeto(['The', 'GATA-3(+)', cells, were, significantly]), verbo([decreased]), complemento([in, the, mild, 'AR', group, compared, with, the, control, group, '(', 'P=0'])]). relacion([sujeto([754, ')', ',', while, they, were, significantly]), verbo([decreased]), complemento([in, the, moderate, and, severe, 'AR', groups, '(', 'P=0'])]). relacion([sujeto(['The', ratio, of, 'T-bet(+)/GATA-3(+)', cells, was, more]), verbo([associated]), complemento([with, 'AR', than, was, the, 'RORgammat(+)/FOXP3(+)', cell, ratio, in, the, early, stage])]). relacion([sujeto(['In', the, 'graft,', the, 'T-bet(+)', and, 'RORgammat(+)', cells, were, significantly]), verbo([increased]), complemento([in, 'mild,', moderate, and, severe, 'AR', groups, compared, with, the, control, group, '(', 'P<0'])]). relacion([sujeto(['The', expression, of, 'GATA-3(+)', cell, was, not, significantly]), verbo([increased]), complemento([in, the, mild, 'AR', group, compared, with, the, control, 'group,', while, it, was, significantly, increased, in, the, moderate, and, severe, 'AR', groups, '(', 'P=0'])]). relacion([sujeto(['Concerning', the, 'FOXP3(+)', 'cells,', no, significant, difference, was]), verbo([found]), complemento([between, the, control, and, mild, 'AR', groups, '(', 'P=0'])]). relacion([sujeto([347, ')', ',', while, they, were, significantly]), verbo([increased]), complemento([in, the, moderate, and, severe, 'AR', groups, '(', 'P<0'])]). relacion([sujeto(['It', seems, that, the, ratio, of, 'T-bet(+)/GATA-3(+)', cells, was, more]), verbo([associated]), complemento([with, 'AR', than, was, 'RORgammat(+)/FOXP3(+)', cells, in, the, early, stage, of, 'rejection,', while, the, ratio, of, 'RORgammat(+)/FOXP3(+)', cells, was, associated, more, with, the, later, but, more, persistent, stage, of, rejection])]). relacion([sujeto(['The', vestibular, 'apparatus,', including, three, semicircular, 'canals,', 'saccule,', 'utricle,', and, their]), verbo([associated]), complemento([sensory, 'organs,', detects, angular, and, linear, acceleration, of, the, head, and, relays, the, information, through, vestibular, neurons, to, vestibular, nuclei, in, the, brainstem])]). relacion([sujeto(['Here,', we, show, that, 'LMO4,', a, 'LIM-domain-only', transcriptional, 'regulator,', is]), verbo([required]), complemento([for, the, formation, of, semicircular, canals, and, their, associated, sensory, cristae])]). relacion([sujeto(['Our', results, demonstrate, that, 'Lmo4', controls, the, development, of, the, dorsolateral, otocyst, into, semicircular, canals, and, cristae, through, two, distinct, 'mechanisms:']), verbo([regulating]), complemento([the, expression, of, otic, specific, genes, and, stimulating, the, proliferation, of, the, dorsolateral, part, of, the, otocyst])]). relacion([sujeto(['Extensive', studies]), verbo([have]), complemento([demonstrated, that, 'Th1', type, immunity, is, predominant, in, 'pre-eclampsia,', but, there, is, little, concern, with, regard, to, the, intracellular, mechanisms, behind, this, initial, 'T-cell', polarization])]). relacion([sujeto(['The', expression, levels, of, 'FOXP3', mRNA, were]), verbo([decreased]), complemento([in, both, 'PBMCs', and, decidua, from, 'pre-eclamptic', patients, compared, with, healthy, pregnant, women, '(', 'P', &, 'lt;', 0.05, ')', ',', and, 'T-bet', mRNA, and, 'RORc', mRNA, were, significantly, increased, '(', 'P', &, 'lt;', 0.05, ')', ',', while, 'Th1/Th2', balance, shifted, toward, the, 'Th1', immunity])]). relacion([sujeto(['Decreased', expression, of, 'FOXP3', mRNA, and]), verbo([increased]), complemento([expression, of, 'T-bet', mRNA, may, contribute, to, 'Th1', type, immunity, predominant, in, 'pre-eclampsia'])]). relacion([sujeto(['An']), verbo([increasing]), complemento([number, of, epidemiological, studies, show, that, exposure, to, farming, environment, during, early, childhood, strongly, influences, the, development, of, allergic, reactions, later, in, life, '(', '\'', hygiene, 'hypothesis\')'])]). relacion([sujeto(['Also,', it, had, been, shown, that, certain, bacteria, from, this, environment, may]), verbo([have]), complemento(['allergy-protective', properties])]). relacion([sujeto([lwoffii, 'F78']), verbo([induced]), complemento([a, 'T(H)1-polarizing', program, in, human, dendritic, cells, which, led, to, 'T(H)1', differentiation])]). relacion([sujeto([lwoffii, 'F78', was, the, responsible, molecule]), verbo([promoting]), complemento([these, effects])]). relacion([sujeto(['We']), verbo([found]), complemento([evidence, that, the, 'allergy-protecting', effects, of, 'A'])]). relacion([sujeto(['Periodontitis', is, a, 'widespread,', complex, inflammatory, disease, of, the, 'mouth,', which, results, in, a]), verbo([loss]), complemento([of, gingival, tissue, and, alveolar, 'bone,', with, aggressive, periodontitis, '(', 'AgP)', as, its, most, severe, form])]). relacion([sujeto(['We']), verbo([found]), complemento(['AgP', to, be, strongly, associated, with, the, intronic, 'SNP', 'rs1537415,', which, is, located, in, the, glycosyltransferase, gene, 'GLT6D1'])]). relacion([sujeto(['The']), verbo([associated]), complemento([rare, 'G', allele, of, rs1537415, showed, an, enrichment, of, 10, '%', in, periodontitis, cases, '(', 48.4, '%', in, comparison, with, 38.8, '%', in, 'controls)'])]). relacion([sujeto(['Sequencing', identified, no, further]), verbo([associated]), complemento([variant])]). relacion([sujeto(['Analysis', of, potential, transcription, factor]), verbo([binding]), complemento([sites, at, this, locus, predicted, a, significant, reduction, of, 'GATA-3', binding, 'affinity,', and, an, electrophoretic, mobility, assay, indicated, a, 'T', cell, specific, reduction, of, protein, binding, for, the, 'G', allele])]). relacion([sujeto(['Overexpression', of, 'GATA-3', in, 'HEK293', cells, resulted, in, 'allele-specific']), verbo([binding]), complemento([of, 'GATA-3,', indicating, the, identity, of, 'GATA-3', as, the, binding, protein])]). relacion([sujeto(['Here', we, show, that, the, basic, 'helix-loop-helix', transcription, factor, 'Dec2', was, selectively]), verbo([expressed]), complemento([in, 'T(H)2', cells])]). relacion([sujeto(['Dec2']), verbo([promoted]), complemento([expression, of, interleukin, 4, '(', 'IL-4),', 'IL-5', and, 'IL-13', during, early, 'T(H)2', differentiation, and, directly, bound, to, and, activated, transcription, of, genes, encoding, the, transcription, factors, 'JunB', and, 'GATA-3'])]). relacion([sujeto(['As', 'GATA-3']), verbo([induces]), complemento(['Dec2', 'expression,', our, findings, also, indicate, a, 'feed-forward', regulatory, circuit, during, 'T(H)2', differentiation])]). relacion([sujeto(['We', show, that, establishment, of, this, boundary, is, concomitant, with, the, induction, of, over, a, thousand, genes, in, intestinal, 'epithelium,', and, these, gene, products]), verbo([provide]), complemento([intestinal, character])]). relacion([sujeto(['Compared', with, the, normal, 'controls,', 'T-bet', mRNA, expression]), verbo([decreased]), complemento([whereas, 'GATA-3', mRNA, expression, increased, significantly, in, patients, with, 'SLE,', active, 'SLE', and, inactive, 'SLE'])]). relacion([sujeto(['The', high, expression, of, 'GATA-3']), verbo([promotes]), complemento([the, immature, 'T', cells, to, differentiate, into, 'Th2', 'cells,', induces, 'Th2', cells, to, secrete, the, cytokines, 'IL-6', and, 'IL-10,', 'which,', along, with, the, low, expression, of, 'Th1', as, a, result, of, 'T-bet', expression, 'inhibition,', causes, 'B', cell, activation, to, produce, a, large, quantity, of, 'autoantibodies,', leading, finally, to, multiple, organ, injuries])]). relacion([sujeto(['Effective', regulation, of, 'GATA-3', expression, may]), verbo([provide]), complemento([a, new, clue, for, the, treatment, of, 'SLE'])]). relacion([sujeto(['Our', previous, studies, illustrated, that, berberine]), verbo([inhibited]), complemento([adipogenesis, in, 'murine-derived', 3, 'T3-L1', preadipocytes, and, human, white, preadipocytes])]). relacion([sujeto(['The', results, demonstrated, that, in, 'FD', 'mice,', berberine, reduced, mouse, weight]), verbo([gain]), complemento([and, food, intake, and, serum, 'glucose,', 'triglyceride,', and, total, cholesterol, levels, accompanied, with, a, 'down-regulation', of, 'PPARgamma', expression, and, an, 'up-regulation', of, 'GATA-3', expression])]). relacion([sujeto(['These', encouraging, findings]), verbo([suggest]), complemento([that, berberine, has, excellent, pharmacological, potential, to, prevent, obesity])]). relacion([sujeto(['The', ileitic, phenotype, may]), verbo([have]), complemento([arisen, during, crosses, of, 'SAMP1', mice, selected, for, the, presence, of, skin, lesions])]). relacion([sujeto(['Histological', features, and, time, course, of, disease, were, 'conserved,', compared, to, those]), verbo([reported]), complemento([in, 'SAMP1/Yit', 'strains,', with, similar, expansion, of, 'CD19+,', 'CD4+,', and, 'CD8+', effector, '(', 'CD44(high)', 'CD62L(low)),', and, central, memory, lymphocytes, '(', 'CD44(high)CD62L(high))'])]). relacion([sujeto(['Lastly,', corticosteroids, attenuated, 'ileitis,', resulting, in]), verbo([decreased]), complemento([lymphocyte, subsets, and, cellularity, of, compartments])]). relacion([sujeto(['Here', we]), verbo([report]), complemento([that, the, ileitic, phenotype, of, 'SAMP1-related', strains, was, already, present, in, the, original, 'SAMP1', strain])]). relacion([sujeto(['Dissemination', of, these, strains, may, advance, our, understanding, of, 'CD', 'pathogenesis,', which, in, 60, '%', of, patients]), verbo([involves]), complemento([the, terminal, ileum])]). relacion([sujeto(['In', order, to, reconstruct, the, molecular, pathways, in, which, a, gene, of, interest, is]), verbo([involved]), complemento([in, regulating, a, 'cell,', it, is, important, to, identify, the, set, of, genes, to, which, it, interacts, with, to, determine, cell, function])]). relacion([sujeto(['We', describe, an, approach, for, the, identification, of, genes, that]), verbo([interact]), complemento([with, each, other, to, regulate, cell, function])]). relacion([sujeto(['Integration', and, analysis, of, 'PPI', data, confirmed, the, prediction, of, the, 'methodology,', since, the, genes, identified, to, be, functionally, related, were]), verbo([associated]), complemento([to, proteins, close, in, the, 'PPI', network])]). relacion([sujeto(['Two', genes, among, the, predicted, putative, partners, of, 'TBX3', '(', 'GLI3', and, 'GATA3)', were, confirmed, by, in, vivo]), verbo([binding]), complemento([assays, '(', crosslinking, 'immunoprecipitation,', 'X-ChIP)', in, which, the, putative, 'DNA', enhancer, sequence, sites, of, 'GATA3', and, 'GLI3', were, found, to, be, bound, by, the, 'Tbx3', protein])]). relacion([sujeto(['The', prediction, of, the, 'TBX3']), verbo([target]), complemento([genes, 'GLI3', and, 'GATA3', was, experimentally, confirmed])]). relacion([sujeto(['The', alpha7, nicotinic, acetylcholine, receptor, '(', 'nAChR)', was, recently, described, as, an, 'anti-inflammatory']), verbo([target]), complemento([in, both, macrophages, and, 'T', cells])]). relacion([sujeto(['Our', results, indicate, that, the, alpha7, nAChR, is]), verbo([expressed]), complemento([on, the, surface, of, 'CD4(+)', 'T', cells, and, that, this, expression, is, 'up-regulated', upon, immune, activation])]). relacion([sujeto(['IL-4', production, was]), verbo([increased]), complemento([in, the, same, setting])]). relacion([sujeto(['Attenuation', of, the, 'Th1', and, 'Th17', lineages, was, accompanied, by, reduced, 'T-bet', '(', 50, '%', ')', and]), verbo([increased]), complemento(['GATA-3', '(', 350, '%', ')', expression])]). relacion([sujeto(['Overall,', nicotine]), verbo([induced]), complemento([a, shift, to, the, 'Th2', lineage])]). relacion([sujeto([')']), verbo([suppressed]), complemento([the, severity, of, 'CD4(+)', 'T', 'cell-mediated', disease, experimental, autoimmune, encephalomyelitis])]). relacion([sujeto(['Accordingly,', 'CD4(+)', and, 'CD11b(+)', cells, infiltration, into, the, 'CNS,', 'demyelination,', and, axonal]), verbo([loss]), complemento([were, reduced])]). relacion([sujeto(['Our', data, implicate, a, role, for, the, alpha7, nAChR, in, immune, modulation, and]), verbo([suggest]), complemento([that, alpha7, nAChR, agonists, may, be, effective, in, the, treatment, of, inflammatory, disorders])]). relacion([sujeto(['The', molecular, mechanisms]), verbo([leading]), complemento([to, the, generation, of, 'T(H)2', responses, remain, 'unclear,', although, 'toll-like', receptors, '(', 'TLRs)', present, on, innate, immune, cells, play, a, pivotal, role, in, sensing, molecular, patterns, and, in, programming, adaptive, 'T', cell, responses])]). relacion([sujeto(['Here', we, show, that, in, vivo, activation, of, 'TLR4', by, house, dust, mite, antigens]), verbo([leads]), complemento([to, the, induction, of, allergic, 'disease,', a, process, that, is, associated, with, expression, of, a, unique, subset, of, 'small,', noncoding, microRNAs])]). relacion([sujeto(['Selective', blockade, of, microRNA, '(', 'miR)-126']), verbo([suppressed]), complemento([the, asthmatic, 'phenotype,', resulting, in, diminished, 'T(H)2', 'responses,', 'inflammation,', airways, 'hyperresponsiveness,', eosinophil, 'recruitment,', and, mucus, hypersecretion])]). relacion([sujeto(['miR-126', blockade, resulted, in, augmented, expression, of, 'POU', domain, class, 2]), verbo([associating]), complemento([factor, 1, ',', which, activates, the, transcription, factor, 'PU'])]). relacion([sujeto(['In', 'summary,', this, study, presents, a, functional, connection, between, miRNA, expression, and, asthma, 'pathogenesis,', and, our, data]), verbo([suggest]), complemento([that, targeting, miRNA, in, the, airways, may, lead, to, 'anti-inflammatory', treatments, for, allergic, asthma])]). relacion([sujeto(['FTY720,', a, sphingosine, 1, -, phosphate, '(', 'S1P)', receptor, 'modulator,']), verbo([suppresses]), complemento([immune, responses, by, inhibiting, 'T-cell', migration, into, target, 'tissues;', 'however,', it, does, not, alter, 'T-cell', functions])]). relacion([sujeto(['Unlike', 'T', 'cells,', 'FTY720']), verbo([suppressed]), complemento([the, production, of, 'IL-4,', 'IFN-gamma,', 'IL-10,', and, 'IL-13', by, 'NKT', cells, through, the, 'S1P1', receptor, '(', 'S1P(1))'])]). relacion([sujeto(['Moreover,', 'FTY720', also]), verbo([inhibited]), complemento([the, expression, of, 'T-bet', and, 'GATA-3', of, 'NKT', cells, in, the, presence, of, 'TCR', engagement])]). relacion([sujeto(['However,', it, did, not]), verbo([inhibit]), complemento(['NKT', cell, migration, in, vitro, or, in, vivo])]). relacion([sujeto(['In', a, 'K/BxN', serum, transfer, arthritis, 'model,', 'FTY720']), verbo([suppressed]), complemento([arthritis, in, 'B6,', but, not, in, 'CD1d(-/-)', mice])]). relacion([sujeto(['Taken', 'together,', these, data, show, that, 'FTY720']), verbo([suppresses]), complemento([cytokine, production, in, 'NKT', cells, through, 'S1P(1),', but, not, 'NKT', cell, migration])]). relacion([sujeto(['Type', 'I', diabetes, mellitus, is]), verbo([caused]), complemento([by, autoimmune, destruction, of, pancreatic, beta, 'cells,', and, effective, treatment, of, the, disease, might, require, rescuing, beta, cell, function, in, a, context, of, reinstalled, immune, tolerance])]). relacion([sujeto(['Sertoli', cells, '(', 'SCs)', are]), verbo([found]), complemento([in, the, 'testes,', where, their, main, task, is, to, provide, local, immunological, protection, and, nourishment, to, developing, germ, cells])]). relacion([sujeto(['SCs']), verbo([have]), complemento([also, been, successfully, implanted, into, the, central, nervous, system, to, create, a, regulatory, environment, to, the, surrounding, tissue, which, is, trophic, and, 'counter-inflammatory'])]). relacion([sujeto(['We']), verbo([report]), complemento([that, isolated, neonatal, porcine, 'SC,', administered, alone, in, highly, biocompatible, 'microcapsules,', led, to, diabetes, prevention, and, reversion, in, the, respective, 88, and, 81, '%', of, overtly, diabetic, '(', nonobese, diabetic, '[', 'NOD])', 'mice,', with, no, need, for, additional, beta, cell, or, insulin, therapy])]). relacion([sujeto(['The', effect, was]), verbo([associated]), complemento([with, restoration, of, systemic, immune, tolerance, and, detection, of, functional, pancreatic, islets, that, consisted, of, 'glucose-responsive', and, 'insulin-secreting', cells])]). relacion([sujeto(['Curative', effects, by, 'SC', were, strictly, dependent, on, efficient, tryptophan, metabolism, in, the, 'xenografts,']), verbo([leading]), complemento([to, 'TGF-beta-dependent', emergence, of, 'autoantigen-specific', regulatory, 'T', cells, and, recovery, of, beta, cell, function, in, the, diabetic, recipients])]). relacion([sujeto(['Foxp3(+)', regulatory, 'T', cells, '(', 'Tregs)', are, crucial, for]), verbo([preventing]), complemento([autoimmunity])]). relacion([sujeto(['We']), verbo([have]), complemento([demonstrated, that, depletion, of, 'Foxp3(+)', 'Tregs', results, in, the, development, of, a, 'scurfy-like', 'disease,', indicating, that, 'Foxp3(-)', effector, 'T', cells, are, sufficient, to, induce, autoimmunity])]). relacion([sujeto(['It']), verbo([has]), complemento([been, postulated, that, nonfunctional, 'Tregs', carrying, potentially, 'self-reactive', 'T', cell, receptors, may, contribute, to, scurfy, '(', 'sf)', pathogenesis, due, to, enhanced, recognition, of, self])]). relacion([sujeto(['Since', 'DEREG', mice]), verbo([express]), complemento(['GFP', under, the, control, of, an, additional, 'Foxp3', 'promoter,', those, crossings, allowed, proving, the, existence, of, &, 'quot;would-be"', 'Tregs,', which, are, characterized, by, 'GFP', expression, in, the, absence, of, functional, 'Foxp3'])]). relacion([sujeto(['Both', 'GFP(+)', and, 'GFP(-)', sf, cells, produced, high, amounts, of, 'Th2-type', 'cytokines,', reflected, also, by]), verbo([enhanced]), complemento(['Gata-3', 'expression,', when, tested, in, vitro])]). relacion([sujeto(['Nevertheless,', sf, 'Tregs', could, be]), verbo([induced]), complemento([in, 'vitro,', although, with, lower, efficiency, than, 'DEREG', 'Tregs'])]). relacion([sujeto(['Transfer', of, 'GFP(+)', sf, 'Tregs,', in, contrast, to, 'GFP(-)', sf, 'T', 'cells,', into, 'RAG1-deficient', animals, did, not]), verbo([cause]), complemento([the, sf, phenotype])]). relacion([sujeto(['Taken', 'together,', natural, and]), verbo([induced]), complemento(['Tregs', develop, in, the, absence, of, 'Foxp3', in, sf, 'mice,', which, lack, both, suppressive, activity, and, autoreactive, 'potential,', but, rather, display, a, 'Th2-biased', phenotype])]). relacion([sujeto(['The', differentiation, of, 'Th17', cells]), verbo([requires]), complemento([the, simultaneous, presence, of, an, unusual, combination, of, 'cytokines:', 'IL-6,', a, proinflammatory, 'cytokine,', and, transforming, growth, factor, '(', 'TGF)', 'beta,', an, antiinflammatory, cytokine])]). relacion([sujeto(['We']), verbo([report]), complemento([that, 'TGF-beta', does, not, directly, promote, 'Th17', cell, differentiation, but, instead, acts, indirectly, by, blocking, expression, of, the, transcription, factors, signal, transducer, and, activator, of, transcription, '(', 'STAT)', 4, and, 'GATA-3,', thus, preventing, 'Th1', and, 'Th2', cell, differentiation])]). relacion([sujeto(['In', 'contrast,', 'TGF-beta', had, no, effect, on, the, expression, of, retinoic, acid, 'receptor-related', orphan]), verbo([nuclear]), complemento([receptor, 'gammat,', a, 'Th17-specific', transcription, factor])]). relacion([sujeto(['Interestingly,', in, 'Stat-6(-/-)T-bet(-/-)', 'mice,', which, are, unable, to, generate, 'Th1', and, 'Th2', 'cells,', 'IL-6', alone, was, sufficient, to]), verbo([induce]), complemento([robust, differentiation, of, 'Th17', 'cells,', whereas, 'TGF-beta', had, no, 'effect,', suggesting, that, 'TGF-beta', is, dispensable, for, 'Th17', cell, development])]). relacion([sujeto(['Collectively,', these, data]), verbo([provide]), complemento([evidence, that, 'TGF-beta', is, not, directly, required, for, the, molecular, orchestration, of, 'Th17', cell, differentiation])]). relacion([sujeto(['Only', a, handful, of]), verbo([target]), complemento([genes, are, known, for, these, two, factors, and, because, of, 'this,', the, mechanism, through, which, 'T-bet', and, 'GATA-3', induce, differentiation, toward, alternative, cell, fates, is, not, fully, understood])]). relacion([sujeto(['Here,', we]), verbo([provide]), complemento([a, genomic, map, of, 'T-bet', and, 'GATA-3', binding, in, primary, human, 'T', cells, and, identify, their, target, 'genes,', most, of, which, are, previously, unknown])]). relacion([sujeto(['In', 'Th1', 'cells,', 'T-bet']), verbo([associates]), complemento([with, genes, of, diverse, 'function,', including, those, with, roles, in, transcriptional, 'regulation,', chemotaxis, and, adhesion])]). relacion([sujeto(['GATA-3', occupies, genes, in, both, 'Th1', and, 'Th2', cells, 'and,', 'unexpectedly,', shares, a, large, proportion, of]), verbo([targets]), complemento([with, 'T-bet'])]). relacion([sujeto(['These', data, show, that, the, choice, between, 'Th1', and, 'Th2', lineage, commitment, is, the, result, of, the, opposing, action, of, 'T-bet', and, 'GATA-3', at, a, shared, set, of]), verbo([target]), complemento([genes, and, may, provide, a, general, paradigm, for, the, interaction, of, 'lineage-specifying', transcription, factors])]). relacion([sujeto([1, is, dynamically]), verbo([regulated]), complemento([during, early, 'T', lineage, development, in, the, thymus])]). relacion([sujeto([1, by, the, 'lck-Cre', transgene, does, not, affect, 'T', cell, 'development,', 'Sfpi1(lck-/-)', 'T', cells]), verbo([have]), complemento([a, lower, activation, threshold, than, 'wild-type', 'T', cells])]). relacion([sujeto(['When', 'TCR', engagement, is, 'limiting,', 'Sfpi1(lck-/-)', 'T', cells, cultured, in, 'Th2', polarizing, conditions, secrete, higher, levels, of, 'Th2', cytokines, and]), verbo([have]), complemento([greater, cytokine, homogeneity, than, 'wild-type', cells])]). relacion([sujeto([1]), verbo([modulates]), complemento([the, levels, of, 'TCR', expression, in, 'CD4(+)', 'T', cells, by, regulating, the, 'DNA-binding', activity, of, 'GATA-3', and, limiting, 'GATA-3', regulation, of, 'TCR', gene, expression])]). relacion([sujeto([1, expression, segregates, into, subpopulations, of, cells, that]), verbo([have]), complemento([lower, levels, of, surface, 'TCR,', suggesting, that, 'PU'])]). relacion([sujeto(['Thus,', we]), verbo([have]), complemento([identified, a, mechanism, whereby, increased, 'GATA-3', function, in, the, absence, of, the, antagonizing, activity, of, 'PU'])]). relacion([sujeto([1]), verbo([leads]), complemento([to, increased, 'TCR', 'expression,', a, reduced, activation, 'threshold,', and, increased, homogeneity, in, 'Th2', populations])]). relacion([sujeto(['It']), verbo([has]), complemento([been, reported, that, the, botanical, 'alkaloids,', berberine, and, evodiamine, inhibit, mouse, preadipocyte, 3, 'T3-L1', differentiation])]). relacion([sujeto(['We']), verbo([have]), complemento([shown, that, treatment, with, 8, microM, berberine, or, 4, microM, evodiamine, resulted, in, a, major, inhibition, of, 'HWP', differentiation, accompanied, by, 'up-regulation', of, both, 'GATA', binding, protein, 2, and, 3, '(', 'GATA-2', and, 'GATA-3)', mRNA, and, protein, 'expression,', suggesting, that, both, compounds, may, have, excellent, potential, as, agents, to, prevent, obesity])]). relacion([sujeto(['DHA', exerted, not, only, an, inhibitory, effect, on, 'T-cell', 'proliferation,', but, also, diminished, 'IFN-gamma', and]), verbo([stimulated]), complemento(['IL-4', secretions, in, both, cell, types])]). relacion([sujeto(['Though', the, 'T-cells', from, 'PPARalpha(null)', mice]), verbo([expressed]), complemento([higher, p38, phosphorylation, than, 'WT', 'T-cells,', 'DHA', diminished, the, 'MAP', kinase, phosphorylation, '(', p38, and, 'ERK1/2)', in, both, the, cell, types])]). relacion([sujeto(['Altogether,', these, results, demonstrate, that, 'DHA,', via, its, action, on, 'MAP', 'kinases,']), verbo([modulates]), complemento([the, expression, of, transcription, factors])]). relacion([sujeto(['There', is]), verbo([increasing]), complemento([evidence, that, the, numerous, mechanisms, that, regulate, cell, differentiation, during, normal, development, are, also, involved, in, tumorigenesis])]). relacion([sujeto(['In', breast, 'cancer,', differentiation, markers]), verbo([expressed]), complemento([by, the, primary, tumor, are, routinely, profiled, to, guide, clinical, decisions])]). relacion([sujeto(['Indeed,', numerous, studies]), verbo([have]), complemento([shown, that, the, differentiation, profile, correlates, with, the, metastatic, potential, of, tumors])]). relacion([sujeto(['The', transcription, factor, 'GATA3']), verbo([has]), complemento([emerged, recently, as, a, strong, predictor, of, clinical, outcome, in, human, luminal, breast, cancer])]). relacion([sujeto(['In', the, mammary, 'gland,', 'GATA3', is]), verbo([required]), complemento([for, luminal, epithelial, cell, differentiation, and, 'commitment,', and, its, expression, is, progressively, lost, during, luminal, breast, cancer, progression, as, cancer, cells, acquire, a, stem, 'cell-like', phenotype])]). relacion([sujeto(['Importantly,', expression, of, 'GATA3', in, 'GATA3-negative,', undifferentiated, breast, carcinoma, cells, is, sufficient, to]), verbo([induce]), complemento([tumor, differentiation, and, inhibits, tumor, dissemination, in, a, mouse, model])]). relacion([sujeto(['We', previously]), verbo([reported]), complemento([that, pancreatic, cancer, patients, have, a, selective, 'Th2', skew, in, the, 'anti-carcinoembryonic', antigen, '(', 'CEA)', 'CD4(+)', 'T', cell, 'immunity,', which, correlates, with, the, presence, of, a, predominant, 'GATA-3(+)', tumor, lymphoid, infiltrate])]). relacion([sujeto(['This']), verbo([has]), complemento([negative, effects, in, both, effective, 'anti-tumor', immunity, and, further, favoring, fibrinogenesis])]). relacion([sujeto(['We']), verbo([found]), complemento([that, only, the, combination, of, 'IL-12', and, 'IL-27', modified, the, polarization, of, 'Th2', effectors, by, both, reduction, of, 'IL-5,', 'GM-CSF', and, 'IL-13', and, induction, of, 'IFN-gamma', 'production,', which, lasted, after, cytokine, removal])]). relacion([sujeto(['In', agreement, with, the, data, obtained, with, the, 'clones,', we]), verbo([found]), complemento([that, the, combined, treatment, functionally, modulated, the, 'Th2', polarization, of, 'CEA-specific', 'CD4(+)', 'T', cells, and, enhanced, 'pre-existing', 'Th1', type, immunity])]). relacion([sujeto(['Hence,', 'loco-regional', cytokines, delivery, or]), verbo([targeted]), complemento([therapy, based, on, antibodies, or, molecules, directed, to, the, tumor, stroma, might, improve, 'anti-tumor', immunity, and, ameliorate, 'fibrosis,', without, systemic, toxicity])]). relacion([sujeto(['A', member, of, 'winged-helix/forkhead', transcription, 'factors,', 'Foxp1,', is]), verbo([expressed]), complemento([in, the, developing, spinal, cord, during, mouse, embryogenesis])]). relacion([sujeto([5, ',', 'Foxp1(high)', neurons]), verbo([increased]), complemento([in, the, ventral, spinal, cord, at, the, limb, levels])]). relacion([sujeto(['All', of, 'Foxp1(high)', neurons, at, the, limb, levels, were, 'Islet2(+)/Lhx3(-)', motor, neurons, '(', 'MNs)', of, the, lateral, motor, column, and, some, neurons, that]), verbo([expressed]), complemento(['Foxp1', weakly, '(', 'Foxp1(low))', at, the, thoracic, level, were, 'MNs', of, the, preganglionic, motor, column])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, 'Foxp1', may, play, some, important, roles, in, the, determination, of, neuronal, fates, of, the, ventral, spinal, 'cord,', possibly, through, the, suppression, of, 'Lhx3', expression])]). relacion([sujeto(['Of', the, 50, 'TFs,', 'Cdx2']), verbo([provoked]), complemento([the, most, extensive, transcriptome, perturbation, in, 'ESCs,', followed, by, 'Esx1,', 'Sox9,', 'Tcf3,', 'Klf4,', and, 'Gata3'])]). relacion([sujeto(['ChIP-Seq', revealed, that, 'CDX2']), verbo([binds]), complemento([to, promoters, of, upregulated, target, genes])]). relacion([sujeto(['By', 'contrast,', genes, downregulated, by, 'CDX2', did, not, show, 'CDX2']), verbo([binding]), complemento([but, were, enriched, with, binding, sites, for, 'POU5F1,', 'SOX2,', and, 'NANOG'])]). relacion([sujeto(['Genes', with]), verbo([binding]), complemento([sites, for, these, core, 'TFs', were, also, downregulated, by, the, induction, of, at, least, 15, other, 'TFs,', suggesting, a, common, initial, step, for, 'ESC', differentiation, mediated, by, interference, with, the, binding, of, core, 'TFs', to, their, target, genes])]). relacion([sujeto(['These', 'ESC', lines]), verbo([provide]), complemento([a, fundamental, resource, to, study, biological, networks, in, 'ESCs', and, mice])]). relacion([sujeto(['A', number, of, methods]), verbo([have]), complemento([been, established, for, identifying, sentinel, nodes, '(', 'SNs)'])]). relacion([sujeto(['In', 'pN1-2,', 'T-BET', expression]), verbo([decreased]), complemento([compared, with, 'pN0(mol+),', but, 'FOXP3', expression, did, not])]). relacion([sujeto(['On', the, other, 'hand,', 'GATA-3', expression, inversely]), verbo([increased]), complemento([in, 'pN1-2', compared, with, 'pN0(mol+)'])]). relacion([sujeto(['In', patients, with, breast, 'cancer,', micrometastasis, can]), verbo([stimulate]), complemento(['Th1', response, in, 'SNs'])]). relacion([sujeto(['However,', the, 'Treg', cell, response, is, also]), verbo([induced]), complemento([at, the, micrometastasis, level, and, persists, during, the, progression, of, metastasis, in, 'SNs'])]). relacion([sujeto(['Then,', the, shift, in, the, 'Th1/Th2', balance, may, preferentially, lean, toward, 'Th2', responses, in, 'pN1-2', 'SNs', and]), verbo([suppress]), complemento([antitumor, immune, responses])]). relacion([sujeto(['We']), verbo([have]), complemento([studied, the, function, of, the, zinc, finger, transcription, factor, gata3, in, auditory, system, development, by, analysing, temporal, profiles, of, gene, expression, during, differentiation, of, conditionally, immortal, cell, lines, derived, to, model, specific, auditory, cell, types, and, developmental, stages])]). relacion([sujeto(['Knock-down', of, gata3, in, vitro, was]), verbo([associated]), complemento([with, a, decrease, in, expression, of, genes, linked, to, 'IGF-signalling,', including, 'IGF1,', 'IGF2', and, several, 'IGF-binding', proteins])]). relacion([sujeto(['It', also]), verbo([led]), complemento([to, a, small, decrease, in, protein, levels, of, the, 'serine-threonine', kinase, 'Akt2/PKBbeta,', a, dramatic, increase, in, 'Akt1/PKBalpha', protein, and, relocation, of, 'Akt1/PKBalpha', from, the, nucleus, to, the, cytoplasm])]). relacion([sujeto(['The', 'cyclin-dependent', kinase, inhibitor, 'p27(kip1),', a, known]), verbo([target]), complemento([of, 'PKB/Akt,', simultaneously, decreased])]). relacion([sujeto(['In', heterozygous, gata3, null, mice, the, expression, of, gata3, correlated, with, high, levels, of]), verbo([activated]), complemento(['Akt/PKB'])]). relacion([sujeto(['This', functional, relationship, could, explain, the, diverse, function, of, gata3, during, 'development,', the, hearing]), verbo([loss]), complemento([associated, with, gata3, heterozygous, null, mice, and, the, broader, symptoms, of, human, patients, with, 'Hearing-Deafness-Renal', anomaly, syndrome])]). relacion([sujeto(['RelB-silenced', 'DCs']), verbo([provide]), complemento([a, practical, means, to, normalize, the, differentiation, of, the, four, 'T-cell', subsets, '(', 'Th17,', 'Th1,', 'Th2,', and, 'Treg)', in, 'vivo,', and, thus, possess, therapeutic, potential, in, 'Th1/Th17-dominant', autoimmune, disorders, such, as, myasthenia, gravis])]). relacion([sujeto(['Cytohesin', binder, and, regulator, '(', 'Cybr)', is, known, to]), verbo([regulate]), complemento([leukocyte, adhesion, and, migration])]). relacion([sujeto(['Cybr']), verbo([inhibited]), complemento([p38, phosphorylation, following, 'CD4(+)', 'T-cell', stimulation])]). relacion([sujeto(['Since', p38]), verbo([regulates]), complemento([the, expression, of, 'T-box', expressed, in, 'T-cells', '(', 'T-bet)', but, not, 'GATA', binding, protein, 3, '(', 'GATA-3)', in, 'T-cells,', 'Cybr', decreased, the, expression, of, 'T-bet', and, 'IFN-gamma', in, 'CD4(+)', 'T-cells'])]). relacion([sujeto(['Moreover,', we]), verbo([found]), complemento([that, host, immunity, against, 'Listeria', infection, and, 'IFN-gamma', production, in, blood, were, significantly, compromised, in, 'Cybr-overexpressing', transgenic, mice])]). relacion([sujeto(['In', 'summary,', our, data]), verbo([suggest]), complemento([that, 'Cybr', represses, the, expression, of, 'T-bet', and, 'IFN-gamma', via, an, inhibition, of, p38, in, 'T-cells', and, consequently, reduces, host, resistance, to, bacterial, infection, in, mice])]). relacion([sujeto(['Even', if, the, biological, effects, of, 'low-level', radiation]), verbo([have]), complemento([been, intensely, debated, and, 'investigated,', the, molecular, mechanisms, underlying, the, cellular, response, to, low, doses, remain, largely, unknown])]). relacion([sujeto(['Chromatin', immunoprecipitation, showed, 'GATA3', to, be, able, to]), verbo([bind]), complemento([the, promoter, of, 4, genes, responding, to, a, 1, cGy, exposure])]). relacion([sujeto(['Knock-down', was, obtained, by, 'lentiviral-mediated', expression, of, an, shRNA]), verbo([targeting]), complemento([the, 'GATA3', transcript, in, differentiated, keratinocytes])]). relacion([sujeto(['First,', radiosensitivity, was, 'assessed:', the, 'toxicity,', in, terms, of, immediate, survival, '(', with, 'XTT', 'test),']), verbo([associated]), complemento([with, 1, cGy, radiation, was, found, to, be, increased, in, 'GATA3', 'knock-down', cells])]). relacion([sujeto(['The', impact, of, 'GATA3', 'knock-down', on, the, transcriptome, of, 'X-ray', irradiated, cells, was, also, 'investigated,', using, oligonucleotide, microarrays, to, assess, changes, between, 3, h, and, 72, h, 'post-irradiation', in, normal, vs, 'GATA3', 'knock-down', 'backgrounds;', transcriptome, response, was]), verbo([found]), complemento([to, be, completely, altered, in, 'GATA3', 'knock-down', 'cells,', with, a, strong, 'induction/repression', peak, 48, h, after, irradiation])]). relacion([sujeto(['Functional', annotation, revealed, enrichment, in, genes, known, to, be]), verbo([involved]), complemento([in, chaperone, 'activity,', 'TGFbeta', signalling, and, stress, response])]). relacion([sujeto(['The', 'zinc-finger', transcription, factors, 'Gata3', and, 'ThPOK']), verbo([have]), complemento([both, been, implicated, in, positive, selection, of, double, positive, '(', 'DP)', thymocytes, towards, the, 'CD4', lineage])]). relacion([sujeto(['As', in, the, absence, of, 'Gata3,', expression, of, 'ThPOK', is, 'lacking,', 'Gata3', may, directly]), verbo([regulate]), complemento(['ThPOK', expression])]). relacion([sujeto(['As', 'ThPOK', failed, to]), verbo([promote]), complemento(['CD4(+)', lineage, differentiation, of, 'Gata3-deficient', 'cells,', 'ThPOK', cannot, be, the, only, 'Gata3', target, gene, essential, for, the, induction, of, the, 'CD4(+)', lineage, program])]). relacion([sujeto(['Here,', we, show, that, 'Gata3', overexpression, does, not, affect, 'ThPOK', expression, levels, in, 'DP', or, 'CD4(+)', 'thymocytes,']), verbo([providing]), complemento([evidence, that, 'Gata3', does, not, directly, regulate, 'ThPOK'])]). relacion([sujeto(['To', identify, additional]), verbo([target]), complemento([genes, that, clarify, 'Gata3', function, at, the, 'DP', thymocyte, 'stage,', we, performed, gene, expression, profiling, assays, in, 'wild-type', mice, and, transgenice, mice, with, enforced, expression, of, 'Gata3,', in, the, presence, or, absence, of, the, 'MHC', class, 'II-restricted', 'DO11'])]). relacion([sujeto(['We']), verbo([found]), complemento([that, 'Gata3', expression, in, 'DP', cells, undergoing, positive, selection, was, associated, with, downregulation, of, the, 'V(D)J-recombination', machinery, genes, 'Rag1,', 'Rag2', and, 'TdT'])]). relacion([sujeto(['Moreover,', 'Gata3', overexpression, was]), verbo([associated]), complemento([with, downregulation, of, many, signaling, molecules, and, the, induction, of, modulators, of, 'TCR', 'signaling,', including, 'Ctla-4', and, thrombospondin, 2])]). relacion([sujeto(['Together', with, our, previous]), verbo([finding]), complemento([that, 'Gata3', reduces, expression, of, 'CD5,', a, negative, regulator, of, 'TCR', 'signaling,', and, upregulates, 'TCR', 'expression,', these, findings, indicate, that, 'Gata3', in, 'DP', cells, mainly, functions, to, '(', 'i)', terminate, 'TCRalpha', gene, 'rearrangement,', and, '(', 'ii)', regulate, 'TCR', signal, intensity, or, duration, in, cells, undergoing, positive, selection, towards, the, 'CD4', lineage])]). relacion([sujeto(['Recently,', reciprocal, regulation, of, 'GATA3', and, 'ER', transcription, was, 'demonstrated,']), verbo([suggesting]), complemento([that, control, of, their, expression, is, intertwined])]). relacion([sujeto(['We', sought, to, determine, whether, 'GATA3', and, 'ER', expression, was, also, coordinately]), verbo([regulated]), complemento([at, other, levels])]). relacion([sujeto(['However,', like, 'ER,', these, inhibitors]), verbo([decreased]), complemento(['GATA3', expression, in, 'ER/GATA3-positive', cell, lines])]). relacion([sujeto(['We']), verbo([have]), complemento([previously, reported, that, 'ER', mRNA, stability, is, increased, through, binding, of, the, 'RNA-binding', protein, 'HuR/ELAV1', to, the, 3, '\'', untranslated, region, '(', 'UTR)', and, that, 'DNMT', and, 'HDAC', inhibitors, reduce, 'ER', expression, by, altering, this, interaction])]). relacion([sujeto(['Biotin', 'pull-down', assays, using, a, biotinylated, 'GATA3', 'RNA', probe, confirmed, that, 'HuR', also]), verbo([binds]), complemento([to, the, 'GATA3', 3, '\'', 'UTR'])]). relacion([sujeto(['Inhibition', of, 'HuR', using, siRNA, probes]), verbo([decreased]), complemento(['GATA3', 'mRNA,', mRNA, stability, and, protein, 'expression,', indicating, that, 'HuR', plays, a, role, in, regulating, 'GATA3', expression])]). relacion([sujeto(['These', findings, may, aid, in, identification, of, new]), verbo([targets]), complemento([that, control, cell, growth, of, breast, cancer, cells])]). relacion([sujeto(['The', 'hypoparathyroidism,', 'deafness,', renal, dysplasia, '(', 'HDR)', syndrome, is]), verbo([caused]), complemento([by, mutations, in, the, gene, encoding, 'GATA3,', which, belongs, to, a, family, of, dual, 'zinc-finger', transcription, factors, that, have, a, role, in, vertebrate, embryonic, development])]). relacion([sujeto(['Western', blot, analysis, and, immunofluorescence, revealed, that, the, mutation, did, not, affect]), verbo([nuclear]), complemento([localization, of, 'GATA3'])]). relacion([sujeto(['However,', 'EMSAs', showed, it, to, reduce, 'DNA']), verbo([binding]), complemento(['affinity,', but, not, 'stability,', and, yeast, 'two-hybrid', assays, demonstrated, that, the, mutant, 'GATA3', resulted, in, a, loss, of, interaction, with, 'ZnF1', and, 'ZnF6', of, the, cofactor, 'FOG2'])]). relacion([sujeto(['The', mutant, 'GATA3', significantly, reduced, luciferase, reporter, activity, by, more, than, 65, '%', '(', 'P', &, 'lt;', 0.001, ')', ',', and, 'three-dimensional', modeling, indicated, that, the, functional, abnormalities, may, be, due, to, a]), verbo([loss]), complemento([of, 'Thr272', polar, side, chain, interaction, with, 'Leu268'])]). relacion([sujeto(['A', novel, missense, 'HDR-associated', 'GATA3', 'mutation,', 'Thr272Ile,']), verbo([has]), complemento([been, identified, and, shown, to, result, in, reduced, 'DNA', 'binding,', a, partial, loss, of, 'FOG2', 'interaction,', and, a, decrease, in, gene, transcription])]). relacion([sujeto([p63]), verbo([binds]), complemento([and, transactivates, the, 'GATA-3', promoter])]). relacion([sujeto(['GATA-3', is]), verbo([expressed]), complemento([late, during, human, skin, development])]). relacion([sujeto(['IL-21', is, a, crucial, regulator, of, 'NK', cell, 'function,', whose, influence, on, 'IL-15-induced', differentiation, of, 'CD34-lineage-', cells]), verbo([has]), complemento([not, been, investigated, previously])]). relacion([sujeto(['CD34-lineage-', cells, were]), verbo([maintained]), complemento([in, liquid, culture, with, 'Flt3-L', and, 'SCF,', with, the, addition, of, 'IL-15', and, 'IL-21,', either, alone, or, in, combination])]). relacion([sujeto(['CD34-lineage-', cells, proliferated, vigorously, in, response, to, 'IL-15', and, 'IL-21', but, not, to, 'IL-21', 'alone,', and, 'up-regulated']), verbo([phosphorylated]), complemento(['Stat1', and, 'Stat3', proteins])]). relacion([sujeto(['IL-21/IL-15-differentiated', cells]), verbo([expressed]), complemento([high, levels, of, mRNA, for, 'Bcl-2,', 'GATA-3', and, 'Id2,', a, master, switch, required, for, 'NK-cell', 'development,', and, harboured, 'un-rearranged', 'TCRgamma', genes])]). relacion([sujeto(['From', a, functional, 'standpoint,', 'IL-21/IL-15-treated', cells, secreted, copious, amounts, of, 'IFN-gamma,', 'GM-CSF', and, 'CCL3/MIP-1alpha,', and]), verbo([expressed]), complemento([cell, surface, 'CD107a', upon, contact, with, 'NK-sensitive', tumour, 'targets,', a, measure, of, exocytosis, of, 'NK', secretory, granules])]). relacion([sujeto(['Although', 'Gata-2,', -, 3, and, 'Fog-2', are]), verbo([expressed]), complemento([in, the, developing, nervous, 'system,', 'Gata-4', was, not, detected])]). relacion([sujeto(['Northern-blot', hybridisation, and, 'real-time', 'RT-PCR']), verbo([suggested]), complemento([specific, expression, patterns, of, the, four, genes, in, primary, 'neuroblastoma,', but, did, not, show, unequivocal, results])]). relacion([sujeto(['During', early, mammalian, 'development,', genesis, of, the, first, two, cell, 'lineages,', inner, cell, mass, '(', 'ICM)', and, trophectoderm, '(', 'TE),', is, dependent, upon, functions, of, key, transcription, factors, that, are]), verbo([expressed]), complemento([in, a, regulated, and, spatially, restricted, fashion])]). relacion([sujeto(['In', this, 'study,', we, demonstrate, that, during, early, mouse, 'development,', mRNA, expression, of, transcription, factor, 'GATA3', is]), verbo([induced]), complemento([at, the, 4, -, cell, stage, and, is, consistently, present, during, 'pre-implantation', embryonic, development])]). relacion([sujeto(['Using', mouse, trophoblast, stem, cells, '(', 'TS', 'cells)', as, a, 'model,', we]), verbo([found]), complemento(['that,', knockdown, of, 'GATA3', by, 'RNA', interference, '(', 'RNAi)', 'down-regulates', expression, of, 'caudal-type', homeobox, 2, '(', 'CDX2),', a, key, regulator, of, the, 'TE', lineage])]). relacion([sujeto(['Chromatin', immunoprecipitation, '(', 'ChIP)', analyses, revealed, 'that,', in, 'TS', 'cells,', 'GATA3', directly]), verbo([regulates]), complemento(['Cdx2', transcription, from, a, conserved, 'GATA', motif, at, the, intron, 1, region, of, the, 'Cdx2', locus])]). relacion([sujeto(['In', 'addition,', 'down-regulation', of, 'GATA3', in, 'pre-implantation', mouse, embryos, reduces, 'Cdx2', expression, and]), verbo([inhibits]), complemento([morula, to, blastocyst, transformation])]). relacion([sujeto(['Our', results, indicate, a, novel, function, of, 'GATA3,', in, which, it, is, selectively]), verbo([expressed]), complemento([in, 'TE,', regulates, expression, of, key, genes, in, 'TE', 'lineage,', and, is, involved, in, morula, to, blastocyst, transformation])]). relacion([sujeto(['Chlamydial', 'Inclusion', membrane, proteins, '(', 'Incs),', are]), verbo([involved]), complemento([in, biochemical, interactions, with, host, cells, and, infecting, 'Chlamydiae'])]). relacion([sujeto(['We']), verbo([have]), complemento([previously, reported, the, role, of, two, 'Chlamydia', trachomatis, '(', 'CT)', 'Incs,', namely, 'IncB', and, 'IncC', in, generating, host, immunity, in, 'CT', infected, women])]). relacion([sujeto(['Emerging', data, shows, involvement, of, 'Inc']), verbo([stimulated]), complemento(['CD4', positive, 'T', cells, in, aiding, host, immunity, in, infected, fertile, and, infertile, women, through, the, secretion, of, interferon, gamma])]). relacion([sujeto(['CD8', 'depleted,', 'CD4', enriched, cervical, cells, were, isolated, and, upon, stimulation, with, 'IncB', and, 'IncC,', modulation, of, cytokines, '(', 'Interleukin', '(', 'IL)-1', 'Beta,', 'IL-4,', 'IL-5,', 'IL-6,', 'IL-10,', 'Interferon-gamma,', 'IL-12,', 'IL-23,', 'Tumor', 'Necrosis', 'Factor-alpha', and, 'Granulocyte', macrophage, 'colony-stimulating', factor, '(', 'GM-CSF)', and, 'T', cell, lineage]), verbo([regulating]), complemento([transcription, factors, 'T-Bet', and, 'GATA3', was, determined, by, 'real-time', 'reverse-transcriptase', '(', 'RT)-PCR', and, 'ELISA'])]). relacion([sujeto(['Significant', higher, expression, '(', 'P', &, 'lt;', 0.05, ')', of, 'Interferon-gamma,', 'IL-12,', 'IL-23', and, 'GM-CSF', were]), verbo([found]), complemento([in, 'Inc-stimulated', 'CD4', enriched, cervical, cells, of, 'CT-positive', fertile, women, and, contrastingly, high, 'IL-1', 'Beta,', 'IL-4,', 'IL-5,', 'IL-6', and, 'IL-10', levels, were, found, in, 'CT-positive', infertile, women])]). relacion([sujeto(['Positive', correlation, '(', 'P', &, 'lt;', 0.05, ')', was]), verbo([found]), complemento([between, 'Interferon-gamma', and, 'T-Bet', levels, in, 'CT-positive', fertile, women, and, 'IL-4', mRNA, and, 'GATA3', levels, in, 'CT-positive', infertile, patients, upon, 'IncB', and, 'IncC', stimulation])]). relacion([sujeto(['Our', study, also]), verbo([suggests]), complemento([that, 'Incs', are, able, to, modulate, expression, of, 'T', cell, lineage, determinants, indicating, their, involvement, in, regulation, of, immune, cells])]). relacion([sujeto(['Several', transcription, factors, are, known, to, control, the, emergence, of, 'CD4', and, 'CD8', 'lineages,', including, the, zinc, finger, proteins, 'Thpok', and, 'Gata3,', which, are]), verbo([required]), complemento([for, 'CD4', lineage, 'differentiation,', and, the, 'Runx', factors, 'Runx1', and, 'Runx3,', which, contribute, to, 'CD8', lineage, differentiation])]). relacion([sujeto(['As', previously, 'shown,', higher, levels, of, 'NOTCH1', and]), verbo([increased]), complemento(['NF-kappaB', signaling, is, a, distinctive, feature, of, the, more, primitive, umbilical, cord, blood, '(', 'UCB)', 'CD34+', hematopoietic, stem, cells, '(', 'HSCs),', as, compared, to, bone, marrow, '(', 'BM)'])]). relacion([sujeto(['Promoter', analysis, on, all, these, 'TF', genes, revealed, a, significantly, higher, frequency, '(', than, expected, by, 'chance)', of, 'NF-kappaB-binding', sites, '(', 'BS),', including, potentially, novel, 'NF-kappaB']), verbo([targets]), complemento([such, as, 'RUNX1,', 'GATA3,', and, 'USF1'])]). relacion([sujeto(['Endothelial', phenotypes, are, highly]), verbo([regulated]), complemento([in, space, and, time, by, both, transcriptional, and, 'post-transcriptional', mechanisms])]). relacion([sujeto(['There', is]), verbo([increasing]), complemento([evidence, that, the, 'GATA', family, of, transcription, factors, function, as, signal, 'transducers,', coupling, changes, in, the, extracellular, environment, to, changes, in, downstream, target, gene, expression])]). relacion([sujeto(['Here', we, show, that, human, primary, endothelial, cells, derived, from, large, blood, vessels]), verbo([express]), complemento(['GATA2,', -, 3, ',', and, -, 6])]). relacion([sujeto(['Of', these, 'factors,', 'GATA3', was]), verbo([expressed]), complemento([at, the, highest, levels])]). relacion([sujeto(['In', 'DNA', microarrays, of, human, umbilical, vein, endothelial, cells, '(', 'HUVEC),', small, interfering, 'RNA-mediated', knockdown, of, 'GATA3', resulted, in, reduced, expression, of, genes]), verbo([associated]), complemento([with, 'angiogenesis,', including, 'Tie2'])]). relacion([sujeto(['At', a, functional, 'level,', 'GATA3', knockdown]), verbo([inhibited]), complemento([angiopoietin, '(', 'Ang)-1-mediated', but, not, vascular, endothelial, cell, growth, factor, '(', 'VEGF)-mediated', 'AKT', 'signaling,', cell, 'migration,', 'survival,', and, tube, formation])]). relacion([sujeto(['In', electrophoretic, gel, mobility, shift, assays, and, chromatin, 'immunoprecipitation,', 'GATA3', was, shown, to]), verbo([bind]), complemento([to, regulatory, regions, within, the, 5, '\'', -, untranslated, region, of, the, 'Tie2', gene])]). relacion([sujeto(['In', 'co-immunoprecipitation', and, 'co-transfection', 'assays,', 'GATA3', and, the, 'Ets', transcription, 'factor,', 'ELF1,', physically]), verbo([interacted]), complemento([and, synergized, to, transactivate, the, 'Tie2', promoter])]). relacion([sujeto(['Together,', these, findings]), verbo([suggest]), complemento([that, 'GATA3', is, indispensable, for, 'Ang-1-Tie2-mediated', signaling, in, large, vessel, endothelial, cells])]). relacion([sujeto(['To', investigate, the, expression, of, 'Th1/Th2', transcription, factors, and, cytokines, in, peripheral, blood, of, patients, with, esophageal, squamous, cell, carcinoma, '(', 'ESCC)', during, radiotherapy, to]), verbo([provide]), complemento([an, evidence, for, using, traditional, 'Chinese', medicine, in, 'anti-tumor', immunotherapy])]). relacion([sujeto(['Radiotherapy', can, not, reverse, the, 'Th1/Th2', shift, presented, in, 'ESCC', 'patients,', while, the, combined, intravenous, dripping, of, 'Aidi', 'Injection', during, radiotherapy, can]), verbo([inhibit]), complemento([it, effectively])]). relacion([sujeto(['The', combined, therapy, could, elevate, the, immune, function, in, 'organism,']), verbo([enhance]), complemento([the, 'radiosensitivity,', and, attenuate, the, 'toxic-adverse', effect, of, radiotherapy])]). relacion([sujeto(['During', the, development, of, the, inner, 'ear,', auditory, and, vestibular, ganglion, neurons, are, generated, in, a, highly]), verbo([regulated]), complemento([sequential, process])]). relacion([sujeto(['The', zinc, finger, transcription, factor, 'Gata3']), verbo([has]), complemento([been, shown, to, play, a, role, in, cell, proliferation, and, differentiation, in, various, regions, of, the, inner, ear])]). relacion([sujeto(['Gata3', is]), verbo([expressed]), complemento([in, a, distinct, population, of, sensorineural, precursor, cells, within, the, otic, 'epithelium,', but, is, not, expressed, in, migrating, or, proliferating, neuroblasts])]). relacion([sujeto(['Following', terminal, 'mitosis,', 'Gata3', expression, is, restricted, to, very, few, cells, in, the, auditory, ganglion, and, is, not]), verbo([expressed]), complemento([in, any, cells, of, the, vestibular, ganglion])]). relacion([sujeto(['Gata3', expression, levels, then]), verbo([increase]), complemento([in, auditory, neurons, as, they, mature])]). relacion([sujeto(['The']), verbo([increase]), complemento([of, 'Gata3', in, auditory, ganglion, neurons, is, accompanied, by, decreased, expression, of, 'NeuroD'])]). relacion([sujeto(['Our', results]), verbo([suggest]), complemento([that, 'Gata3', may, be, specifically, involved, in, the, differentiation, of, auditory, ganglion, neurons])]). relacion([sujeto(['Expression', of, 'T1ST2,', the, 'IL-33R,', by, 'Th2', cells]), verbo([requires]), complemento(['GATA3'])]). relacion([sujeto(['Resting', 'Th2', cells]), verbo([express]), complemento([little, 'GATA3,', which, is, increased, by, 'IL-33', and, a, 'STAT5', 'activator,', in, turn, increasing, 'T1ST2', from, its, 'low-level', expression, on, resting, 'Th2', cells])]). relacion([sujeto(['Th2', cells, that]), verbo([have]), complemento([upregulated, 'T1ST2', produce, 'IL-13,', but, not, 'IL-4,', in, response, to, 'IL-33', plus, a, 'STAT5', activator, in, an, 'antigen-independent,', 'NF-kappaB-dependent,', cyclosporin, 'A', '(', 'CsA)-resistant', manner])]). relacion([sujeto(['Thus,', each, effector, 'Th', cell, produces, cytokines, without, antigenic, stimulation, in, response, to, an, 'IL-1', family, member, and, a, specific, 'STAT', 'activator,', implying, an, innate, mechanism, through, which, memory, 'CD4', 'T', cells, are]), verbo([recruited]), complemento([by, an, induced, cytokine, environment])]). relacion([sujeto(['The', 'Polycomb', group, protein, enhancer, of, zeste, homolog, 2, '(', 'EZH2),', which]), verbo([has]), complemento([roles, during, development, of, numerous, 'tissues,', is, a, critical, regulator, of, cell, type, identity])]). relacion([sujeto(['Overexpression', of, 'EZH2']), verbo([has]), complemento([been, detected, in, invasive, breast, carcinoma, tissue, samples, and, is, observed, in, human, breast, tissue, samples, of, morphologically, normal, lobules, up, to, 12, years, before, the, development, of, breast, cancer])]). relacion([sujeto(['To', investigate, the, role, of, 'EZH2', in, the, mammary, 'gland,', we]), verbo([targeted]), complemento([the, expression, of, 'EZH2', to, mammary, epithelial, cells, using, the, mouse, mammary, tumor, virus, long, terminal, repeat])]). relacion([sujeto(['In', 'addition,', remodeling, of, the, mammary, gland, after, parturition, was, impaired, and, 'EZH2', overexpression]), verbo([caused]), complemento([delayed, involution])]). relacion([sujeto(['Mechanistically,', we]), verbo([found]), complemento([that, 'EZH2', physically, interacts, with, 'beta-catenin,', inducing, 'beta-catenin', nuclear, accumulation, in, mammary, epithelial, cells, and, activating, 'Wnt/beta-catenin', signaling])]). relacion([sujeto(['The', differentiation, of]), verbo([activated]), complemento(['CD4(+)', 'T', cells, into, the, 'T', helper, type, 1, '(', 'T(H)1)', or, 'T(H)2', fate, is, regulated, by, cytokines, and, the, transcription, factors, 'T-bet', and, 'GATA-3'])]). relacion([sujeto(['Here', we, show, that, early, 'GATA-3', 'expression,']), verbo([required]), complemento([for, 'T(H)2', 'differentiation,', was, induced, by, 'T', cell, factor, 1, '(', 'TCF-1)', and, its, cofactor, 'beta-catenin,', mainly, from, the, proximal, 'Gata3', promoter, upstream, of, exon, 1, b])]). relacion([sujeto(['This', activity, was]), verbo([induced]), complemento([after, 'T', cell, antigen, receptor, '(', 'TCR)', stimulation, and, was, independent, of, 'IL-4', receptor, signaling, through, the, transcription, factor, 'STAT6'])]). relacion([sujeto(['Furthermore,', 'TCF-1', blocked, 'T(H)1', fate, by, negatively]), verbo([regulating]), complemento(['interferon-gamma', '(', 'IFN-gamma)', expression, independently, of, 'beta-catenin'])]). relacion([sujeto(['Thus,', 'TCF-1', initiates, 'T(H)2', differentiation, of]), verbo([activated]), complemento(['CD4(+)', 'T', cells, by, promoting, 'GATA-3', expression, and, suppressing, 'IFN-gamma', expression])]). relacion([sujeto(['Nasal', polyposis]), verbo([has]), complemento([different, etiologies, in, 'Western', and, 'Eastern', countries])]). relacion([sujeto(['To', determine, the, 'T-cell', phenotypes]), verbo([involved]), complemento([in, nasal, polyposis, in, 'Chinese', patients])]). relacion([sujeto(['Increased', expression, of, 'CD4+', and, 'CD8+', and]), verbo([decreased]), complemento([expression, of, 'Foxp3', and, 'IL-17', were, detected, in, nasal, polyps, compared, with, control, tissue])]). relacion([sujeto(['Furthermore,']), verbo([increased]), complemento([levels, of, 'IFN-gamma,', 'IL-4', and, 'IL-5', and, decreased, levels, of, 'IL-10', and, 'TGF-beta', were, found, in, nasal, polyps])]). relacion([sujeto(['Our', findings, demonstrate, that, excessive, infiltration, of, 'CD4+', and, 'CD8+', 'T', cells, in, nasal, polyps, may, be]), verbo([associated]), complemento([with, expression, of, 'Foxp3+', by, 'Tregs', but, not, with, 'SAEs', in, 'Chinese', patients])]). relacion([sujeto(['We', sought, to, determine, whether, the, levels, of, expression, of, 17, candidate, genes, were]), verbo([associated]), complemento([with, locoregional, control, after, 'breast-conserving', treatments, of, 'early-stage', breast, cancers, in, 'young,', premenopausal, women])]). relacion([sujeto(['In', univariate, 'analysis,', no, 'clinical/pathologic', prognostic, factors, were]), verbo([found]), complemento([to, be, significantly, associated, with, decreased, locoregional, control])]). relacion([sujeto(['Expression', of, three, genes, was]), verbo([found]), complemento([to, be, significantly, associated, with, an, increased, locoregional, recurrence, 'rate:', low, 'estrogen-receptor', 'beta,', low, 'aromatase,', and, high, 'GATA3'])]). relacion([sujeto(['Two', others, were]), verbo([associated]), complemento([with, only, a, trend, '(', 'P', &, 'lt;', 0.1, ')', :, low, 'HER1', and, 'SKP2'])]). relacion([sujeto(['In', multivariate, 'analysis,', only, the, absence, of, aromatase, was, significantly]), verbo([associated]), complemento([with, an, increased, locoregional, recurrence, rate, '(', 'P', =, 0.003, ;, relative, risk, =, 0.49, ;, 95, '%', 'CI', 0.29, to, 0.82, ')'])]). relacion([sujeto(['During', vertebrate, lens, 'development,', the, 'anterior,', 'ectoderm-derived', lens, vesicle, cells, differentiate, into, a, monolayer, of, epithelial, cells, that]), verbo([retain]), complemento([proliferative, potential])]). relacion([sujeto(['In', the, present, 'study,', we, demonstrate, that, the, transcription, factor, 'GATA-3', is]), verbo([expressed]), complemento([in, the, posterior, lens, fiber, cells, during, 'embryogenesis,', and, that, 'GATA-3', deficiency, impairs, lens, development])]). relacion([sujeto(['This']), verbo([suppressed]), complemento([differentiation, is, accompanied, by, an, abnormal, cellular, 'proliferation,', as, well, as, with, diminished, levels, of, the, 'cell-cycle', inhibitors, 'Cdkn1b/p27', and, 'Cdkn1c/p57', and, increased, 'Ccnd2/cyclin', 'D2', abundance])]). relacion([sujeto(['Thus,', these, observations]), verbo([suggest]), complemento([that, 'GATA-3', is, essential, for, lens, cells, differentiation, and, proper, cell, cycle, control])]). relacion([sujeto(['Estrogen-related', receptor, alpha, '(', 'ERRalpha)', is, an, orphan]), verbo([nuclear]), complemento(['receptor,', the, expression, of, which, correlates, with, negative, prognosis, in, breast, cancer])]). relacion([sujeto(['ERRalpha', shares, functional, features, with, the, estrogen, receptor, alpha, '(', 'ERalpha)', and, its, activity, is]), verbo([modulated]), complemento([by, the, 'ERBB2', signaling, pathway])]). relacion([sujeto(['Using', 'genome-wide']), verbo([binding]), complemento([sites, location, analyses, in, 'ERalpha-positive', and, 'ERalpha-negative', breast, cancer, cell, 'lines,', we, show, that, 'ERRalpha', and, 'ERalpha', display, strict, binding, site, specificity, and, maintain, independent, mechanisms, of, transcriptional, activation])]). relacion([sujeto(['Nonetheless,', 'ERRalpha', and, 'ERalpha', coregulate, a, small, subset, of, common]), verbo([target]), complemento([genes, via, binding, either, to, a, 'dual-specificity', binding, site, or, to, distinct, cognate, binding, sites, located, within, the, extended, promoter, region, of, the, gene])]). relacion([sujeto(['Although', 'ERRalpha', signaling, in, breast, cancer, cells, is, mostly, independent, of, 'ERalpha,', the, small, fraction, of, common, 'ERRalpha/ERalpha']), verbo([targets]), complemento([comprises, genes, with, high, relevance, to, breast, tumor, 'biology,', including, genes, located, within, the, 'ERBB2', amplicon, and, 'GATA3'])]). relacion([sujeto(['Finally,', unsupervised, hierarchical, clustering, based, on, the, expression, profiling, of, 'ERRalpha', direct]), verbo([target]), complemento([genes, in, human, breast, tumors, revealed, four, main, clusters, that, recapitulate, established, tumor, subtypes])]). relacion([sujeto(['Herein,', we]), verbo([provide]), complemento([evidence, that, 'Kruppel-like', factor, 10, '(', 'KLF10/TIEG1)', constitutes, an, important, regulator, of, 'T', regulatory, cell, suppressor, function, and, 'CD4(+)CD25(-)', 'T', cell, activation, through, distinct, mechanisms, involving, transforming, growth, factor, '(', 'TGF)-beta1', and, 'Foxp3'])]). relacion([sujeto(['KLF10', overexpressing, 'CD4(+)CD25(-)', 'T', cells]), verbo([induced]), complemento([both, 'TGF-beta1', and, 'Foxp3', 'expression,', an, effect, associated, with, reduced, 'T-Bet', '(', 'Th1', 'marker)', and, 'Gata3', '(', 'Th2', 'marker)', mRNA, expression])]). relacion([sujeto(['Consistently,', 'KLF10(-/-)', 'CD4(+)CD25(-)', 'T', cells]), verbo([have]), complemento([enhanced, differentiation, along, both, 'Th1', and, 'Th2', pathways, and, elaborate, higher, levels, of, 'Th1', and, 'Th2', cytokines])]). relacion([sujeto(['Furthermore,', 'KLF10(-/-)', 'CD4(+)CD25(-)', 'T', cell, effectors, cannot, be, appropriately]), verbo([suppressed]), complemento([by, 'wild-type', 'T', regs])]). relacion([sujeto(['Surprisingly,', 'KLF10(-/-)', 'T', reg, cells]), verbo([have]), complemento([reduced, suppressor, 'function,', independent, of, 'Foxp3', 'expression,', with, decreased, expression, and, elaboration, of, 'TGF-beta1,', an, effect, completely, rescued, by, exogenous, treatment, with, 'TGF-beta1'])]). relacion([sujeto(['Mechanistic', studies, demonstrate, that, in, response, to, 'TGF-beta1,', 'KLF10', can, transactivate, both, 'TGF-beta1', and, 'Foxp3', 'promoters,', implicating, 'KLF10', in, a, positive, feedback, loop, that, may]), verbo([promote]), complemento(['cell-intrinsic', control, of, 'T', cell, activation])]). relacion([sujeto(['Finally,', 'KLF10(-/-)', 'CD4(+)CD25(-)', 'T', cells]), verbo([promoted]), complemento([atherosclerosis, by, approximately, 2, -, fold, in, 'ApoE(-/-)/scid/scid', mice, with, increased, leukocyte, accumulation, and, peripheral, 'pro-inflammatory', cytokines])]). relacion([sujeto(['Thus,', 'KLF10', is, a, critical, regulator, in, the, transcriptional, network, controlling, 'TGF-beta1', in, both, 'CD4(+)CD25(-)', 'T', cells, and, 'T', regs, and, plays, an, important, role, in]), verbo([regulating]), complemento([atherosclerotic, lesion, formation, in, mice])]). relacion([sujeto(['Expression', of, 'interferon-tau', '(', 'IFNT),', necessary, for, pregnancy, establishment, in, ruminant, 'ungulates,', is]), verbo([regulated]), complemento([in, a, temporal, and, spatial, manner])]). relacion([sujeto(['However,', molecular, mechanisms, by, which, 'IFNT', gene, transcription, is]), verbo([regulated]), complemento([in, this, manner, have, not, been, firmly, established])]). relacion([sujeto(['In', this, 'study,', 'DNA', 'microarray/RT-PCR', analysis, between, bovine, trophoblast, 'CT-1', and, 'Mardin-Darby', bovine, kidney, '(', 'MDBK)', cells, was, initially, 'performed,']), verbo([finding]), complemento([that, transcription, factors, 'GATA2,', 'GATA3,', and, 'GATA6', mRNAs, were, specific, to, 'CT-1', cells])]). relacion([sujeto(['These', mRNAs, were, also]), verbo([found]), complemento([in, 'Days', 17, ',', 20, ',', and, 22, '(', 'Day', 0, =, day, of, 'estrus)', bovine, conceptuses])]). relacion([sujeto(['In', examining, other, bovine, cell, 'lines,', ovary, cumulus, granulosa, '(', 'oCG)', and, ear, fibroblast, '(', 'EF)', 'cells,', 'GATA2', and, 'GATA3,', but, not, 'GATA6,', were]), verbo([found]), complemento([specific, to, the, bovine, trophoblast, cells])]). relacion([sujeto(['One', 'Point', mutation, studies, revealed, that, among, six, potential, 'GATA']), verbo([binding]), complemento([sites, located, on, the, upstream, region, of, the, bIFNT, 'gene,', the, one, next, to, 'ETS2', site, exhibited, reduced, luciferase, activity])]). relacion([sujeto(['These', data]), verbo([suggest]), complemento([that, 'GATA2/3', is, involved, in, 'trophoblast-specific', regulation, of, bIFNT, gene, transcription])]). relacion([sujeto(['We']), verbo([have]), complemento([previously, described, an, analog, peptide, of, type, 'II', collagen, '(', 'CII)', that, can, suppress, 'collagen-induced', arthritis, '(', 'CIA)'])]). relacion([sujeto(['When', we]), verbo([found]), complemento([that, 'APCs', pulsed, with, 'A9', failed, to, induce, 'T', cell, phosphorylation, of, 'TCR-zeta', and, 'ZAP-70,', we, explored, alternative, signaling, pathways])]). relacion([sujeto(['We', determined, that, 'A9', instead]), verbo([induced]), complemento([phosphorylation, of, spleen, tyrosine, kinase, '(', 'Syk)'])]). relacion([sujeto(['The', importance, of, 'Syk', was, confirmed, by, the, use, of, chemical, 'Syk', 'inhibitors,', which, blocked, both, cytokine, secretion, and, activation, of, 'GATA-3']), verbo([mediated]), complemento([by, peptide, 'A9'])]). relacion([sujeto(['In', 'summary,', 'T', cells, use, an, alternative, pathway, in, response, to, 'A9', that]), verbo([involves]), complemento(['Syk'])]). relacion([sujeto(['V(D)J', recombination]), verbo([involves]), complemento([the, stepwise, assembly, of, 'B', and, 'T', cell, receptor, genes, as, lymphocytes, progress, through, the, early, stages, of, development])]). relacion([sujeto(['While', the, mechanisms, that, restrict, each, step, in, recombination, to, its, appropriate, developmental, stage, are, largely, 'unknown,', they, share, many, of, the, components, that]), verbo([regulate]), complemento([transcription])]). relacion([sujeto(['We']), verbo([have]), complemento([previously, shown, that, 'Dbeta2', is, flanked, by, upstream, and, downstream, 'promoters,', with, the, 5, '\'', promoter, being, held, inactive, until, 'D-to-J', recombination, deletes, the, 'NFkappaB-dependent', 3, '\'', promoter])]). relacion([sujeto(['We', now]), verbo([report]), complemento([that, activity, of, the, 5, '\'', promoter, reflects, a, complex, interplay, among, 'Runx1,', 'GATA-3,', and, 'E47', transcription, factors])]). relacion([sujeto(['In', 'particular,', while, multiple, 'E47', and, 'Runx1']), verbo([binding]), complemento([sites, clustered, near, the, 'Dbeta2', 5, '\'', 'RS', and, overlapping, inr, elements, define, the, core, 5, '\'', 'PDbeta2,', they, act, in, concert, with, an, array, of, upstream, 'GATA-3', sites, to, overcome, the, inhibitory, effects, of, a, 110, bp, distal, polypurine])]). relacion([sujeto(['The', dependence, of, 5, '\'', 'PDbeta2', on, 'E47', is, consistent, with, the]), verbo([reported]), complemento([role, of, 'E', proteins, in, 'post-DN1', thymocyte, development, and, 'V-to-DJbeta', recombination])]). relacion([sujeto(['We']), verbo([have]), complemento([identified, and, characterized, the, 'full-length', 'Atlantic', salmon, 'GATA-3', cDNA, '(', 3074, 'bp),', having, two, zinc, finger, domains, which, are, fully, conserved, within, teleosts, and, higher, vertebrates])]). relacion([sujeto(['RT-PCR', analysis, revealed, that, the, 'Atlantic', salmon, 'GATA-3', '(', 'AsGATA-3)', is, strongly]), verbo([expressed]), complemento([in, 'gills,', 'thymus,', and, brain])]). relacion([sujeto(['Furthermore,', we]), verbo([have]), complemento([determined, 1.9, kb, of, upstream, promoter, sequence, and, found, a, number, of, sequence, motifs, which, match, those, of, known, transcription, factor, binding, sites, and, the, 'AsGATA-3', promoter, is, a, 'TATA-less', promoter])]). relacion([sujeto(['This', study]), verbo([provides]), complemento([further, insights, into, the, transcriptional, regulation, of, 'AsGATA-3'])]). relacion([sujeto(['To', understand, the, underlying, 'mechanisms,', we, observed, that, mRNA, levels, of, 'Deltex1,', as, well, as, 'Deltex4,', were, dramatically, elevated, in, 'Id1-expressing', 'thymocytes,', which, could, result, in, developmental]), verbo([arrest]), complemento([by, attenuating, 'Notch', function])]). relacion([sujeto(['In', support, of, this, 'hypothesis,', we]), verbo([found]), complemento([that, 'Deltex1', ablation, enabled, 'Id1-expressing', progenitors, to, differentiate, to, the, 'DN3', '(', 'CD44(-)', 'CD25(+))', 'stage,', which, was, accompanied, by, enhanced, 'Notch1', expression, in, 'T-cell', progenitors])]). relacion([sujeto(['Furthermore,', we, showed, that, 'Gfi1b', levels, 'decreased,', whereas, 'GATA3', levels]), verbo([increased]), complemento([in, 'Id1', transgenic, thymocytes])]). relacion([sujeto(['T(H)2', bias, correlates, with, the, amount, of, 'IL-4', initially, secreted, by, newly]), verbo([activated]), complemento([helper, 'T', cells, that, feeds, back, positively, through, the, pathway, of, the, 'IL-4', receptor, and, the, transcription, factors, 'STAT6', and, 'GATA-3', to, drive, 'T(H)2', development])]). relacion([sujeto(['Mina', specifically]), verbo([bound]), complemento([to, and, repressed, the, 'Il4', promoter])]). relacion([sujeto(['Mina', overexpression, in, transgenic, mice, impaired, 'Il4', 'expression,', whereas, its, knockdown, in, primary, 'CD4(+)', 'T', cells]), verbo([led]), complemento([to, 'Il4', derepression])]). relacion([sujeto(['Our', findings, collectively]), verbo([provide]), complemento([mechanistic, insight, into, an, 'Il4-regulatory', pathway, that, controls, helper, 'T', cell, differentiation, and, genetic, variation, in, 'T(H)2', bias])]). relacion([sujeto(['Determining']), verbo([binding]), complemento([sites, of, transcription, factors, is, important, for, understanding, the, transcriptional, control, of, target, genes])]). relacion([sujeto(['Although', a, transcription, factor, 'GATA3', plays, a, pivotal, role, in, 'Th2', lymphocyte, 'development,', its, physiological, role, is, not, clearly, defined, because, the]), verbo([target]), complemento([genes, remain, largely, unknown])]). relacion([sujeto(['In', this, 'study,', we, modified, chromatin, immunoprecipitation, '(', 'ChIP),', and, isolated, 121, 'GATA3']), verbo([binding]), complemento([sites, and, 83, different, annotated, target, genes])]). relacion([sujeto(['Re-ChIP', analysis, using, 'anti-GATA3', and, 'anti-RNA', polymerase, 'II', mAbs, and, chromosome, conformation, capture, assay, demonstrate, that, 'GATA3-bound', fragments]), verbo([interact]), complemento([with, basal, transcriptional, units, of, target, genes])]). relacion([sujeto(['GATA3', regulation, of]), verbo([target]), complemento([genes, under, the, control, of, binding, fragments, was, confirmed, by, reporter, assay, and, quantification, of, target, gene, mRNA, expression, in, the, presence, of, 'GATA', inhibitor, or, short, interfering, 'RNA', against, 'GATA3'])]). relacion([sujeto(['These', data, demonstrate, that, 'GATA3']), verbo([binds]), complemento([to, regulatory, elements, and, controls, target, gene, expression, through, physical, interaction, with, core, promoter, regions])]). relacion([sujeto(['Stemucronatoside', 'L', '(', 'SML),', isolated, from, 'Stephanotis', 'mucronata,', could]), verbo([suppress]), complemento([the, activation, of, 'T', cells, in, vitro])]). relacion([sujeto(['The', purpose, of, this, study, was, to, investigate, whether, 'SML', could]), verbo([suppress]), complemento(['Th1/Th2', immune, responses, and, to, characterize, the, cellular, mechanisms, involved])]). relacion([sujeto(['SML', not, only, significantly]), verbo([decreased]), complemento([the, percentage, of, 'CD4(+)', 'T', cells, and, the, 'CD4(+)/CD8(+)', 'ratio,', but, reduced, the, production, of, 'Th1/Th2', cytokines, in, a, 'concentration-dependent', manner])]). relacion([sujeto(['The', mRNA, expression, levels, of, 'Th1/Th2', cytokines, and, transcription, factors, '(', 'T-bet', and, 'GATA-3)', were, also]), verbo([suppressed]), complemento([by, 'SML'])]). relacion([sujeto(['These', results]), verbo([suggested]), complemento([that, 'SML', could, simultaneously, inhibit, 'Th1/Th2', immune, responses, by, suppressing, gene, expression, of, 'Th1/Th2', cytokines, and, transcription, factors])]). relacion([sujeto(['Microarray', analyses]), verbo([have]), complemento([revealed, that, forkhead, box, 'A1', '(', 'FOXA1)', and, 'GATA', binding, protein, 3, '(', 'GATA-3)', are, expressed, in, close, association, with, 'ERalpha,', both, encoding, for, transcription, factors, with, a, potential, involvement, in, the, 'ERalpha-mediated', action, in, breast, cancer])]). relacion([sujeto(['The', purpose, of, this, study, was, to, explore, if, the, expression, of, 'FOXA1', and, 'GATA-3', may]), verbo([provide]), complemento([an, opportunity, to, stratify, subsets, of, patients, that, could, have, better, 'outcome,', among, the, 'ERalpha-negative/poor', prognosis, breast, cancer, group])]). relacion([sujeto(['We', evaluate, 'FOXA1', and, 'GATA-3', expression, in, 249, breast, carcinomas, by, 'immunohistochemistry,']), verbo([associating]), complemento([it, with, breast, cancer, molecular, 'markers,', clinicopathological, features, and, 'patient\'s', survival])]). relacion([sujeto(['FOXA1', expression, was, inversely]), verbo([associated]), complemento([with, tumour, 'size,', 'Nottingham', 'Prognostic', 'Index,', histological, 'grade,', lymph, vascular, 'invasion,', lymph, node, stage, and, human, epidermal, growth, factor, 'receptor-2', '(', 'HER-2)', 'overexpression,', while, 'GATA-3', expression, showed, inverse, association, with, histological, grade, and, 'HER-2'])]). relacion([sujeto(['Both', 'FOXA1', and, 'GATA-3', were, directly]), verbo([associated]), complemento([with, 'ERalpha', and, progesterone, receptor])]). relacion([sujeto(['In', the, subset, of, 'ERalpha-negative', 'patients,', those, who, were, 'FOXA1-negative', had, a, 3.61, -, fold]), verbo([increased]), complemento([risk, of, breast, cancer, recurrence, when, compared, with, the, 'FOXA1-positive'])]). relacion([sujeto(['Our', results, revealed, that, the, 'DBD', glycoprotein, '(', 200, microg, 'ml(-1))', significantly, attenuated, the, expressions, of, interleukin, '(', 'IL)-4', and, 'IL-10,', whereas]), verbo([enhanced]), complemento([the, expression, of, interferon, '(', 'IFN)-gamma', in, 'OVA', '(', 100, microg, 'ml(-1))-treated', primary, cultured, lymphocytes])]). relacion([sujeto(['We', also]), verbo([found]), complemento([that, the, 'DBD', glycoprotein, has, inhibitory, effects, on, phosphorylations, of, signal, transducer, and, activator, of, transcription, '(', 'STAT)-6,', 'p44/42', 'mitogen-activated', protein, kinase, '(', 'MAPK)', and, p38, 'MAPK', in, primary, cultured, lymphocytes])]). relacion([sujeto(['Interestingly,', the, 'DBD', glycoprotein]), verbo([suppressed]), complemento([the, transcriptional, activation, of, 'GATA-binding', protein, 3, '(', 'GATA-3),', whereas, it, enhanced, the, activity, of, 't-box', expressed, in, 'T', cells, '(', 'T-bet)', in, 'OVA-stimulated', lymphocytes])]). relacion([sujeto(['The', results, from, these, experiments, indicated, that, the, 'DBD', glycoprotein]), verbo([inhibits]), complemento([expressions, of, 'IL-4', and, 'IL-10', through, modulation, of, 'GATA-3,', 'STAT-6,', 'p44/42', 'MAPK', and, p38, 'MAPK', in, mouse, lymphocytes])]). relacion([sujeto(['To', 'date,', whether, 'CD44']), verbo([has]), complemento([a, role, in, regulating, 'Th1-Th2', differentiation, has, not, been, determined])]). relacion([sujeto(['We', observed, that, deficiency, of, 'CD44', tended, to]), verbo([inhibit]), complemento(['Th1', while, promoting, 'Th2', differentiation])]). relacion([sujeto(['Furthermore,', chimeric, studies]), verbo([suggested]), complemento([that, 'CD44', expression, by, 'CD4', 'T', cells, was, essential, for, such, 'Th2', bias])]). relacion([sujeto(['The', regulation, by, 'CD44', occurred, at, the, transcription, level]), verbo([leading]), complemento([to, 'up-regulated', 'GATA3', and, 'down-regulated', 'T-bet', expression, in, activated, 'CD4', 'T', cells])]). relacion([sujeto(['We', also, noted, that, 'CD44-deficiency', could, modify, the, state, of, dendritic, cell, subsets, to]), verbo([induce]), complemento([a, 'Th2-biased', development])]). relacion([sujeto(['Results', presented, in, this, study, demonstrate, for, the, first, time, that, 'CD44']), verbo([participates]), complemento([in, the, regulation, of, 'Th1-Th2', differentiation])]). relacion([sujeto(['Understanding', immune, responses, of, 'white-tailed', deer, '(', 'WTD)', to, infection, with, 'Mycobacterium', bovis]), verbo([provides]), complemento([insight, into, mechanisms, of, pathogen, control, and, may, provide, clues, to, development, of, effective, vaccine, strategies])]). relacion([sujeto(['Recall', 'T-cell', responses, were, measured, by, assessing, the, relative, expression, of, gamma, interferon, '(', 'IFN-gamma),', 'T-cell-specific', 'T-box', transcription, factor, '(', 'Tbet),', interleukin, 12, p40, '(', 'IL-12p40),', 'IL-12p35,', 'IL-23p19,', 'FoxP3,', 'IL-17,', and, 'GATA3', in, 'PBL']), verbo([stimulated]), complemento([in, vitro, with, purified, protein, derivative, '(', 'PPD)', of, 'M'])]). relacion([sujeto(['Animals', vaccinated, with, 'BCG', 'Danish']), verbo([expressed]), complemento([more, 'IFN-gamma', and, 'Tbet', than, either, 'BCG', 'Pasteur-vaccinated', animals, or, unvaccinated, controls])]). relacion([sujeto(['BCG', 'Pasteur-vaccinated', animals]), verbo([expressed]), complemento([more, 'GATA3', than, either, group])]). relacion([sujeto(['After', 'infection,', unvaccinated, controls]), verbo([expressed]), complemento([more, 'Tbet', and, 'IL-12p40', than, vaccinated, animals])]). relacion([sujeto(['BCG', 'Pasteur-vaccinated', animals]), verbo([expressed]), complemento([more, 'GATA3', than, either, the, unvaccinated, controls, or, the, 'BCG', 'Danish-vaccinated', animals, after, infection])]). relacion([sujeto(['Animals', in, the, visible, lesion, group]), verbo([expressed]), complemento([more, 'Tbet', and, 'IFN-gamma', than, animals, that, were, culture, 'negative,', while, 'Tbet', and, 'IFN-gamma', expression, in, the, 'culture-positive,', 'no-visible-lesion', group, was, intermediate])]). relacion([sujeto(['A', 'GATA', motif, at, +, 220]), verbo([has]), complemento([been, implicated, in, basal, 'VWF', expression, in, vitro])]). relacion([sujeto(['Other', studies]), verbo([have]), complemento([shown, that, 'GATA3', and, 'VWF', are, transcriptionally, downregulated, in, response, to, inflammatory, mediators])]). relacion([sujeto(['Our', goal, was, to, determine, the, importance, of, the, +, 220, 'GATA', motif, in]), verbo([mediating]), complemento([expression, of, 'VWF', promoter, in, 'vivo,', and, to, elucidate, whether, the, 'GATA', element, plays, a, role, in, spatial, 'and/or', temporal, regulation, of, 'VWF', expression])]). relacion([sujeto(['Reporter', gene, constructs, containing, 3.6, kb, of, the, human, 'VWF', promoter, with, and, without, a, mutation, of, the, +, 220, 'GATA', element, were, transfected, into, cultured, endothelial, cells, or]), verbo([targeted]), complemento([to, the, 'Hprt', locus, of, mice])]). relacion([sujeto(['In', 'protein-DNA']), verbo([binding]), complemento(['assays,', the, +, 220, 'GATA', motif, bound, 'GATA-2,', -, 3, and, -, 6])]). relacion([sujeto(['When']), verbo([targeted]), complemento([to, the, 'Hprt', locus, of, 'mice,', the, 'GATA', mutation, resulted, in, a, 'significant,', proportionate, reduction, of, promoter, activity, in, 'LacZ', expressing, vascular, beds])]). relacion([sujeto(['To', study, glaucoma, infiltration, surgery]), verbo([induced]), complemento([the, anterior, chamber, associated, immune, deviation, '(', 'ACAID)', by, with, or, without, anterior, chamber, '(', 'AC)', implantation, of, foreign, epithelium, removed, corneal, graft, in, mice])]). relacion([sujeto(['In', this, 'study,', fifty, 'Wistar', mice, were, randomly, divided, into, five, groups, '(', ten, in, each, 'group)', and, additional, five, 'SD', and, one, 'Wistar', mouse, were, used, as, the, providers, of, epithelium, removed, corneal, grafts, to]), verbo([induce]), complemento(['ACAID', as, 'follows:', 'Group', 'A:', corneal, grafts, from, 'Wistar', mouse, were, implanted, into, the, 'AC', 1, week, after, the, infiltration, surgery])]). relacion([sujeto(['To']), verbo([induce]), complemento([the, delayed, type, hypersensitivity, '(', 'DTH),', spleen, cells, were, injected, into, the, right, ear, pinna, 1, week, after, the, neck, injection, in, group, 'B,', 2, weeks, after, the, 'AC', implantation, of, corneal, grafts, in, other, groups])]). relacion([sujeto(['(', 1, ')', 'The', 'DTH', were]), verbo([found]), complemento([in, group, 'B,', 'C,', 'D,', and, 'E', with, corneal, grafts, of, 'SD,', but, not, in, group, 'A', with, that, of, 'Wistar'])]). relacion([sujeto(['The', eye, with, the, glaucoma, infiltration, surgery, results, in, a, temporary, incapable, of]), verbo([inducing]), complemento(['ACAID,', which, is, gradually, recovered, following, the, diminish, of, intraocular, inflammation, and, the, increase, of, levels, of, 'IL4,', 'IL-10', and, 'GATA-3', mRNA])]). relacion([sujeto(['The']), verbo([loss]), complemento([of, expression, of, the, transcription, factor, 'GATA3', in, breast, tumors, has, been, linked, to, aggressive, tumor, development, and, poor, patient, survival])]). relacion([sujeto(['Specifically,', 'GATA3', expression]), verbo([inhibits]), complemento([breast, cancer, cell, expansion, inside, the, lung, parenchyma])]). relacion([sujeto(['This', phenotype, correlates, with, the, ability, of, 'GATA3', to, negatively]), verbo([regulate]), complemento([the, expression, of, several, genes, that, promote, breast, cancer, lung, metastasis, '(', 'ID1/-3,', 'KRTHB1,', 'LY6E', and, 'RARRES3)'])]). relacion([sujeto(['We', conclude, that, 'GATA3']), verbo([inhibits]), complemento([primary, breast, tumor, outgrowth, and, reduces, lung, metastatic, burden, by, regulating, key, genes, involved, in, metastatic, breast, tumor, progression])]). relacion([sujeto(['Here', we, describe, a, transgenic, mouse, model, in, which, the, 'V2a', interneurons]), verbo([have]), complemento([been, ablated, by, targeted, expression, of, diphtheria, toxin, 'A', chain, '(', 'DTA)', under, the, control, of, the, 'Chx10', gene, promoter, '(', 'Chx10::DTA', 'mice)'])]). relacion([sujeto(['The', 'speed-dependent']), verbo([loss]), complemento([of, 'left-right', alternation, is, recapitulated, during, 'drug-induced', fictive, locomotion, in, spinal, cords, isolated, from, neonatal, 'Chx10::DTA', 'mice,', and, 'high-speed', fictive, locomotion, evoked, by, caudal, spinal, cord, stimulation, also, shows, synchronous, 'left-right', bursting])]). relacion([sujeto(['These', results, show, that, spinal, 'V2a', interneurons, are]), verbo([required]), complemento([for, maintaining, 'left-right', alternation, at, high, speeds])]). relacion([sujeto(['Whether', animals, that, generate, galloping, or, hopping, 'gaits,', characterized, by, synchronous, movement, of, left, and, right, forelegs, and, 'hindlegs,']), verbo([have]), complemento([lost, or, modified, the, function, of, 'V2a', interneurons, is, an, intriguing, question])]). relacion([sujeto(['An', imbalance, of, 'Th1', and, 'Th2', cytokines]), verbo([has]), complemento([been, reported, in, 'MCNS'])]). relacion([sujeto(['Interleukin-13', '(', 'IL-13:', 'Th2', 'cytokine)']), verbo([has]), complemento([been, implicated, in, the, pathogenesis, of, 'MCNS,', but, 'Th1/Th2', regulators, such, as, 'T-bet', '(', 'Th1-specific', transcription, 'factor)', and, 'GATA-3', '(', 'Th2-specific', transcription, 'factor)', have, not, been, examined])]). relacion([sujeto(['This', study, is, the, first, to]), verbo([reveal]), complemento([increased, mRNA, expression, levels, of, 'GATA-3', and, 'Stat5A', in, 'PBMC', from, 'MCNS', patients, in, nephrosis])]). relacion([sujeto(['This', study, also, supports, recent, findings]), verbo([suggesting]), complemento([the, role, of, 'IL-13', in, the, development, of, 'MCNS'])]). relacion([sujeto(['A', predominant, 'Th2', type, of, 'T', cell, activation, may, be]), verbo([involved]), complemento([in, the, pathogenesis, of, 'MCNS'])]). relacion([sujeto(['Two', members, of, 'winged-helix/forkhead', transcription, 'factors,', 'Foxp1', and, 'Foxp2,', are]), verbo([expressed]), complemento([in, the, developing, and, adult, 'CNS,', including, the, 'striatum,', cerebral, 'cortex,', and, thalamus])]). relacion([sujeto(['In', a, previous, 'study,', we]), verbo([have]), complemento([demonstrated, that, 'Foxp1', is, expressed, in, a, subpopulation, of, 'V1', interneurons, in, addition, to, motor, neurons, of, the, spinal, cord, during, mouse, embryogenesis])]). relacion([sujeto(['In', 'addition,', neither, 'Foxp1', nor, 'Foxp2', was]), verbo([expressed]), complemento([in, ventral, 'calbindin(+)', 'Renshaw', cells])]). relacion([sujeto(['These', findings]), verbo([suggest]), complemento([that, 'Foxp1', and, 'Foxp2', are, expressed, in, the, distinct, subsets, of, 'V1', interneurons, that, belong, to, 'non-Renshaw', cells, in, the, ventral, spinal, cord, during, embryogenesis])]). relacion([sujeto(['Thus,', 'Foxp1', and, 'Foxp2', may, be]), verbo([involved]), complemento([in, the, determination, of, the, cell, type, identities, during, late, 'embryogenesis:', the, classes, of, neurotransmitters, and, the, functional, subtypes, of, 'non-Renshaw', 'cells,', such, as, 'Ia', and, 'Ib', inhibitory, interneurons])]). relacion([sujeto(['The', overexpression, of, 'GATA-3', in, patients, with, allergic, rhinitis, was, related, to, the]), verbo([increase]), complemento([of, 'ICAM-1'])]). relacion([sujeto(['Sauchinone,', a, lignan, compound, isolated, from, the, root, of, 'Saururus', 'chinensis,']), verbo([has]), complemento([been, recently, demonstrated, to, exhibit, 'anti-inflammatory', activity, via, the, suppression, of, 'NF-kB', p65, activity, in, vitro])]). relacion([sujeto(['In', an, effort, to, evaluate, the, in, vivo, 'anti-inflammatory', function, of, 'sauchinone,', we]), verbo([have]), complemento([evaluated, the, effects, of, sauchinone, on, 'allergen-induced', airway, inflammation, using, a, murine, model, of, allergic, asthma])]). relacion([sujeto(['We', observed, that, marked, eosinophilic, and, lymphocyte, infiltration, in, the, 'BAL', fluid, were]), verbo([suppressed]), complemento([to, a, significant, degree, by, 'sauchinone,', and, that, 'mucus-secreting', goblet, cell, hyperplasia, and, collagen, deposition, in, the, airways, were, also, ameliorated, by, administration, of, sauchinone, treatment])]). relacion([sujeto(['Moreover,', gene, expression, of, the, inflammatory, 'cytokines,', 'IL-13,', and, 'IL-5', and, eotaxin, in, the, 'lung,', and, 'IL-5', in, the, draining, lymph, node, were, significantly]), verbo([decreased]), complemento([in, 'sauchinone-treated', mice])]). relacion([sujeto(['We', demonstrated, that, sauchinone, repressed, 'Th2', cell, development, in, vitro, and, 'IL-4', production, by, 'Th2', 'cells,', and, also]), verbo([inhibited]), complemento(['GATA-3-mediated', 'IL-5', promoter, activity, in, a, 'dose-dependent', manner])]). relacion([sujeto(['We', previously]), verbo([reported]), complemento([in, an, 'ovalbumin-induced', model, of, allergic, asthma, that, 'Fms-like', tyrosine, kinase, 3, ligand, '(', 'Flt3-L)', reversed, airway, hyperresponsiveness, '(', 'AHR)', and, airway, 'inflammation,', and, increased, the, number, of, regulatory, 'CD11c(high)CD8', 'alpha(high)CD11b(low)', dendritic, cells, in, the, lung])]). relacion([sujeto(['Flt3-L', significantly]), verbo([decreased]), complemento([levels, of, 'BALF', 'IL-5,', 'IFN-gamma,', eosinophilia, and, substantially, increased, 'IL-10', and, the, number, of, 'CD4(+)CD25(+)', 'Forkhead', winged, helix, transcription, factor, box, 'P3', '(', 'Foxp3(+))', 'IL-10(+)', 'T', cells, in, the, lung])]). relacion([sujeto(['Administration', of, 'PC61', antibody, blocked, the, effect, of, 'Flt3-L', and, substantially]), verbo([increased]), complemento(['AHR,', 'eosinophilia,', and, 'BALF', 'IL-5', and, 'IFN-gamma', 'levels,', and, decreased, 'BALF', 'IL-10', levels, and, the, number, of, 'CD4(+)CD25(+)Foxp3(+)IL-10(+)', 'T', cells])]). relacion([sujeto(['Flt3-L', significantly]), verbo([decreased]), complemento(['CD62-L,', but, increased, inducible, costimulatory, molecule, and, 'Foxp3', mRNA, expression, in, the, 'CD4(+)CD25(+)', 'T', cells, isolated, from, lungs, of, 'Flt3-L-treated,', 'CRA-sensitized', mice, compared, to, 'CRA-sensitized', mice, without, 'Flt3-L', treatment, and, 'PBS', control, group])]). relacion([sujeto(['Flt3-L', significantly]), verbo([inhibited]), complemento([the, effect, of, 'CRA', sensitization, and, challenge, to, increase, 'GATA3', expression, in, lung, 'CD4(+)CD25(+)', 'T', cells])]). relacion([sujeto(['Collectively,', these, data]), verbo([suggest]), complemento([that, the, therapeutic, effect, of, 'Flt3-L', is, mediated, by, increased, density, of, naturally, occurring, 'CD4(+)CD25(+)Foxp3(+)IL-10(+)ICOS(+)', 'T-regulatory', cells, in, the, lung])]). relacion([sujeto(['Our', results, revealed, that, the, 'CTB', glycoprotein, in, the, presence, of, 'DEHP']), verbo([inhibits]), complemento([the, translocation, of, 'PKC', from, cytosol, to, membrane, and, the, phosphorylation, of, 'p44/42', 'MAPK', in, primary, cultured, 'T', lymphocytes])]). relacion([sujeto(['We', also]), verbo([found]), complemento([that, the, 'CTB', glycoprotein, '(', 100, 'microg/ml)', has, suppressive, effects, on, transcriptional, activation, of, 'STAT6,', 'GATA3,', and, on, the, expression, level, of, 'IL-4', in, 'DEHP-treated', 'T', lymphocytes])]). relacion([sujeto(['The', results, from, these, experiments, indicated, that, the, 'CTB', glycoprotein]), verbo([inhibits]), complemento(['IL-4', 'expression,', not, 'IL-10', 'expression,', on, the, stage, of, 'Th2', cell, differentiation, induced, by, 'DEHP', in, 'T', lymphocytes])]). relacion([sujeto(['Hence,', we, speculate, that, the, 'CTB', glycoprotein]), verbo([has]), complemento([a, strong, inhibitory, ability, for, expressions, of, 'allergy-related', cytokines, indirectly, caused, by, 'DEHP', in, 'Th2', cell, differentiation, of, the, primary, cultured, mouse, 'T', lymphocytes])]). relacion([sujeto(['The', combined, effects, of, mixtures, of, different, species, of, probiotic, bacteria]), verbo([have]), complemento([been, explored, only, in, part])]). relacion([sujeto(['Both', live, and, sonicated, 'VSL#3', preparations]), verbo([induced]), complemento([maturation, and, cytokine, production, by, 'BM-DCs'])]). relacion([sujeto(['Cytokine', production, by, spleen, cells, from, naïve, or, 'Par', j, 1, -, sensitized, mice, was]), verbo([modulated]), complemento([by, the, probiotic, preparations, towards, a, 'Treg/Th0', 'profile,', characterized, by, increased, 'IL-10', and, 'IFN-gamma', production])]). relacion([sujeto(['In', vivo, prophylactic, treatment, with, 'VSL#3']), verbo([induced]), complemento([a, significant, reduction, of, serum, specific, 'IgG1'])]). relacion([sujeto(['At', lung, 'level,', 'VSL#3', 'pre-treatment', remarkably, reduced, 'IL-13', and, 'IL-4', mRNA, expression, and]), verbo([increased]), complemento(['IL-10', expression])]). relacion([sujeto(['The', 'VSL#3', preparations]), verbo([have]), complemento([not, only, the, capacity, to, bias, primary, immune, responses, towards, a, 'Treg/Th0-type', 'profile,', but, also, to, modify, in, the, same, way, the, functional, characteristics, of, established, in, vitro, 'Th2', responses])]). relacion([sujeto(['In', vivo, studies, on, a, mouse, model, of, 'Par', j, 1, sensitization, indicate, that, the, prophylactic, intranasal, treatment, with, probiotic, bacteria, is, able, to]), verbo([modulate]), complemento([the, development, of, 'Th2-biased', responses])]). relacion([sujeto(['GATA-3', plays, a, critical, role, in]), verbo([regulating]), complemento([the, expression, of, the, cytokines, interleukin, '(', 'IL)-4,', 'IL-5,', and, 'IL-13', from, 'T', 'helper-2', '(', 'Th2)', cells, and, therefore, is, a, key, mediator, of, allergic, diseases])]). relacion([sujeto(['Corticosteroids', are, highly, effective, in]), verbo([suppressing]), complemento([allergic, 'inflammation,', but, their, effects, on, 'GATA-3', are, unknown])]). relacion([sujeto(['In', a, 'T', lymphocyte, cell, line, '(', 'HuT-78)', and, peripheral, blood, mononuclear, cells]), verbo([stimulated]), complemento([by, 'anti-CD3', and, 'anti-CD28', in, vitro, we, demonstrated, that, fluticasone, inhibits, nuclear, translocation, of, 'GATA-3', and, expression, of, 'Th2', cytokines, via, a, mechanism, independent, of, nuclear, 'factor-kappaB', and, is, 'due,', in, 'part,', to, competition, between, 'GATA-3', and, the, 'ligand-activated', glucocorticoid, receptor, for, nuclear, transport, through, the, nuclear, importer, 'importin-alpha'])]). relacion([sujeto(['In', 'addition,', fluticasone]), verbo([induces]), complemento([the, expression, of, 'mitogen-activated', protein, kinase, '(', 'MAPK)', 'phosphatase-1', '(', 'MKP-1),', the, endogenous, inhibitor, of, p38, 'MAPK,', which, is, necessary, for, 'GATA-3', nuclear, translocation])]). relacion([sujeto(['We', also, demonstrated, that, inhaled, fluticasone]), verbo([inhibits]), complemento(['GATA-3', nuclear, translocation, in, peripheral, blood, lymphocytes, of, patients, with, asthma, in, vivo])]). relacion([sujeto(['Corticosteroids']), verbo([have]), complemento([a, potent, inhibitory, effect, on, 'GATA-3', via, two, interacting, mechanisms, that, potently, suppress, 'Th2', cytokine, expression])]). relacion([sujeto(['Of', 7, phosphatidylinositol, 3, -, 'kinase/AKT', pathway, phosphorylation, 'sites,', 6, were, more, highly]), verbo([phosphorylated]), complemento([in, 'MBCs', than, in, other, breast, tumor, subtypes])]). relacion([sujeto(['PIK3CA', 'mutations,', 'EMT,', and, stem, 'cell-like', characteristics, likely, contribute, to, the, poor, outcomes, of, 'MBC', and]), verbo([suggest]), complemento([novel, therapeutic, targets])]). relacion([sujeto(['Histone', 'H3', lysine, 4, methylation, '(', 'H3K4me)']), verbo([has]), complemento([been, proposed, as, a, critical, component, in, regulating, gene, 'expression,', epigenetic, 'states,', and, cellular, identities1])]). relacion([sujeto(['The', biological, meaning, of, 'H3K4me', is, interpreted, by]), verbo([conserved]), complemento([modules, including, plant, homeodomain, '(', 'PHD)', fingers, that, recognize, varied, 'H3K4me', states])]). relacion([sujeto(['The', dysregulation, of, 'PHD', fingers]), verbo([has]), complemento([been, implicated, in, several, human, 'diseases,', including, cancers, and, immune, or, neurological, disorders])]). relacion([sujeto(['Here', we]), verbo([report]), complemento([that, fusing, an, 'H3K4-trimethylation', '(', 'H3K4me3)-binding', 'PHD', 'finger,', such, as, the, 'carboxy-terminal', 'PHD', finger, of, 'PHF23', or, 'JARID1A', '(', also, known, as, 'KDM5A', or, 'RBBP2),', to, a, common, fusion, partner, 'nucleoporin-98', '(', 'NUP98)', as, identified, in, human, 'leukaemias,', generated, potent, oncoproteins, that, arrested, haematopoietic, differentiation, and, induced, acute, myeloid, leukaemia, in, murine, models])]). relacion([sujeto(['In', these, 'processes,', a, 'PHD', finger, that, specifically]), verbo([recognizes]), complemento(['H3K4me3/2', marks, was, essential, for, leukaemogenesis])]). relacion([sujeto(['Mutations', in, 'PHD', fingers, that, abrogated, 'H3K4me3']), verbo([binding]), complemento([also, abolished, leukaemic, transformation])]). relacion([sujeto(['NUP98-PHD', fusion]), verbo([prevented]), complemento([the, 'differentiation-associated', removal, of, 'H3K4me3', at, many, loci, encoding, 'lineage-specific', transcription, factors, '(', 'Hox(s),', 'Gata3,', 'Meis1,', 'Eya1', and, 'Pbx1),', and, enforced, their, active, gene, transcription, in, murine, haematopoietic, 'stem/progenitor', cells])]). relacion([sujeto(['Mechanistically,', 'NUP98-PHD', fusions]), verbo([act]), complemento([as, '\'', chromatin, boundary, 'factors\',', dominating, over, 'polycomb-mediated', gene, silencing, to, '\'', 'lock\'', developmentally, critical, loci, into, an, active, chromatin, state, '(', 'H3K4me3', with, induced, histone, 'acetylation),', a, state, that, defined, leukaemia, stem, cells])]). relacion([sujeto(['Collectively,', our, studies, 'represent,', to, our, 'knowledge,', the, first]), verbo([report]), complemento([that, deregulation, of, the, 'PHD', 'finger,', an, '\'', 'effector\'', of, specific, histone, 'modification,', perturbs, the, epigenetic, dynamics, on, developmentally, critical, 'loci,', catastrophizes, cellular, fate, 'decision-making,', and, even, causes, oncogenesis, during, mammalian, development])]). relacion([sujeto(['Exposure', to, 'valproate,', thalidomide, and, alcohol, during, gestation, are, amongst, the, environmental]), verbo([triggers]), complemento([that, are, associated, with, the, development, of, 'ASD'])]). relacion([sujeto(['These', teratogens, may, disturb, the, ontogeny, of, the, brain, by, altering, the, expression, pattern, of, genes, that]), verbo([regulate]), complemento([the, normal, development, of, the, brain])]). relacion([sujeto(['In', this, 'study,', a, 'neuron-like', 'PC-12', cell, model, was, used, to, examine, the, effects, of, these, compounds, on, the]), verbo([binding]), complemento([potential, of, 50, different, transcription, factors, to, understand, the, molecular, 'mechanism/s', that, may, be, involved, in, the, teratogenesis, caused, by, these, agents])]). relacion([sujeto(['Cells', in, culture, were, treated, with, low, or, high, concentrations, of, teratogens, within, a, range, that, are]), verbo([reported]), complemento([in, the, blood, of, individuals])]). relacion([sujeto(['A', pronounced]), verbo([increase]), complemento([in, 'GATA', transcription, factor, binding, was, observed, for, all, three, teratogens])]). relacion([sujeto(['Furthermore,', 'Western', blot, analysis, showed, that, 'GATA-3', level, in, the]), verbo([nuclear]), complemento([fractions, was, enhanced, by, each, of, the, three, teratogens])]). relacion([sujeto(['Results']), verbo([suggest]), complemento([that, altered, gene, expression, pattern, due, to, heightened, 'GATA-3', activities, in, the, fetral, brains, following, exposure, to, these, teratogens, may, contribute, to, the, development, of, 'ASD'])]). relacion([sujeto(['Although', the]), verbo([increased]), complemento([number, of, 'ST1', compared, with, 'ST0', cells, indicates, the, initiation, of, a, proliferation, wave, in, the, very, early, stages, of, iNKT, cell, 'development,', details, about, the, controlling, mechanism, are, currently, lacking])]). relacion([sujeto(['Here,', we, show, that, the, transcription, factor, 'c-Myc', is]), verbo([required]), complemento([for, iNKT, cell, development])]). relacion([sujeto(['In', 'contrast,', annexin, 'V', staining, did, not]), verbo([reveal]), complemento([increased, 'apoptosis,', and, transgenic, overexpression, of, 'BCL-2', did, not, rescue, iNKT, cell, development, in, 'c-Myc-deficient', mice])]). relacion([sujeto(['These,', findings]), verbo([provide]), complemento([compelling, evidence, that, 'c-Myc', mediates, an, intrathymic, proliferation, wave, immediately, after, agonist, selection, of, iNKT, cells, and, illustrate, the, importance, of, this, expansion, for, the, generation, of, mature, iNKT, cells, in, vivo])]). relacion([sujeto(['Previous', studies]), verbo([suggest]), complemento([the, involvement, of, lymphocytes, but, the, phenotypes, of, these, cells, have, never, been, analyzed])]). relacion([sujeto(['Here,', we]), verbo([report]), complemento([the, first, study, of, mRNAs, for, specific, markers, of, 'CD4+', 'T', cells, including, 'Th1', '(', 'T-bet', and, 'INFgamma),', 'Th2', '(', 'IL4', and, 'GATA3),', 'Treg', '(', 'Foxp3)', and, 'Th17', '(', 'IL-17', and, 'RORgammat)', 'subsets,', cytotoxic, 'CD8', 'T', cells, '(', 'Granzyme', 'B)', and, 'B-cell', markers, '(', 'CD20)', in, renal, biopsies, from, renal, transplant, recipients, suffering, interstitial, fibrosis, and, tubular, atrophy, '(', 'IF/TA)', with, or, without, 'TGP', but, with, a, similar, inflammatory, score, and, controls, including, transplant, recipients, with, normal, renal, function])]). relacion([sujeto(['Only', 'INFgamma,', 'T-bet', '(', both, functionally, defined, markers, of, 'Th1', 'CD4', 'T', 'cells)', and, granzyme, 'B', '(', a, 'CD8', cytotoxic, 'marker)', were, significantly, more, strongly]), verbo([expressed]), complemento([in, patients, with, 'TGP', than, in, patients, without, 'TGP', and, normal, controls])]). relacion([sujeto(['T', regulatory, '(', 'Treg)', cells]), verbo([have]), complemento([been, detected, in, periodontitis, 'lesions,', and, forkhead, box, 'P3', '(', 'Foxp3)', expression, has, been, negatively, correlated, to, receptor, activator, of, nuclear, 'factor-kappa', 'B', ligand, '(', 'RANKL)'])]). relacion([sujeto(['These', results]), verbo([lead]), complemento([us, to, speculate, that, 'Foxp3(+)', cells, that, do, not, have, a, regulatory, function, might, have, a, role, in, the, pathogenesis, of, active, periodontal, lesions, by, 'down-regulating', 'TGF-beta1', and, 'IL-10', synthesis, that, lead, to, the, 'over-expression', of, 'Th17-associated', cytokines, 'RANKL', and, 'IL-17'])]). relacion([sujeto(['Mammary', epithelia, are, composed, of, luminal, and, 'myoepithelial/basal', cells, whose, neoplastic, transformations]), verbo([lead]), complemento([to, distinct, types, of, breast, cancers, with, diverse, clinical, features])]). relacion([sujeto(['We']), verbo([report]), complemento([that, mice, deficient, for, the, 'CDK4/6', inhibitor, 'p18(Ink4c)', spontaneously, develop, 'ER-positive', luminal, tumors, at, a, high, penetrance])]). relacion([sujeto(['Ink4c', deletion]), verbo([stimulates]), complemento([luminal, progenitor, cell, proliferation, at, pubertal, age, and, maintains, an, expanded, luminal, progenitor, cell, population, throughout, life])]). relacion([sujeto(['We', demonstrate, that, 'GATA3']), verbo([binds]), complemento([to, and, represses, 'INK4C', transcription])]). relacion([sujeto(['Hence,', 'p18(INK4C)', is, a, downstream]), verbo([target]), complemento([of, 'GATA3,', constrains, luminal, progenitor, cell, 'expansion,', and, suppresses, luminal, tumorigenesis, in, the, mammary, gland])]). relacion([sujeto(['Gene', expression, profiling]), verbo([has]), complemento([classified, breast, tumours, into, five, major, subtypes, with, significant, different, outcome])]). relacion([sujeto(['A', panel, of, three, antibodies, '(', 'Ki67,', 'P53', and, 'GATA3)']), verbo([associated]), complemento([with, 'VPI', can, significantly, improve, the, traditional, prognosticators, in, predicting, outcome, for, 'ER-positive', breast, cancer, patients, receiving, hormonal, therapy])]). relacion([sujeto(['It', is, known, that, a, number, of, transcription, factors, are, key, regulators, in, the, complex, process, of, adipocyte, differentiation, including, peroxisome, proliferator]), verbo([activated]), complemento([receptor, gamma, '(', 'PPARgamma)', and, the, 'CCAAT', enhancer, binding, protein, alpha, '(', 'C/EBPalpha)'])]). relacion([sujeto(['Studies']), verbo([have]), complemento([demonstrated, that, in, 'pre-adipocyte', 3, 'T3-L1', cells, constitutive, expression, of, the, 'DNA', binding, proteins, 'GATA-2', and, 'GATA-3', results, in, 'protein/protein', interactions, with, 'C/EBPalpha', resulting, in, down, regulation, of, 'PPARgamma', and, subsequent, suppressed, adipocyte, differentiation, with, cells, trapped, at, the, 'pre-adipocyte', stage])]). relacion([sujeto(['Thus', it, appears, that, 'GATA-2', and, 'GATA-3', are, of, critical, importance, in]), verbo([regulating]), complemento([adipocyte, differentiation, through, molecular, interactions, with, 'PPARgamma', and, 'C/EBPalpha'])]). relacion([sujeto(['Recent']), verbo([reports]), complemento([suggest, that, 'berberine,', an, isoquinoline, derivative, alkaloid, isolated, from, many, medicinal, herbs, prevents, differentiation, of, 3, 'T3-L1', cells, via, a, down, regulation, of, 'PPARgamma', and, 'C/EBPalpha', expression])]). relacion([sujeto(['Results', show, that, following, treatment, with, 8, microM, berberine, the, mRNA, and, protein, expression, levels, of, 'GATA-2', and, 3, were, elevated, and, accompanied, by]), verbo([inhibited]), complemento([adipocyte, differentiation])]). relacion([sujeto(['These', results, may]), verbo([lead]), complemento([to, the, use, of, berberine, to, target, the, induction, of, specific, genes, such, as, 'GATA-2', and, 'GATA-3', which, affect, adipocyte, differentiation])]). relacion([sujeto(['Then', analysis, of, 'Logistic', regression, equation, and, 'ROC', curves, were, performed, based, on, the, cases]), verbo([responding]), complemento([to, 'IST', or, androgens])]). relacion([sujeto(['Human', 'ICOS', deficiency]), verbo([has]), complemento([been, identified, worldwide, in, nine, patients, with, identical, 'ICOS', mutations])]). relacion([sujeto(['In', vitro, studies, of, the, patients, to, date]), verbo([have]), complemento([shown, only, mild, 'T', cell, defect])]). relacion([sujeto(['In', this, 'study,', we]), verbo([report]), complemento([an, 'in-depth', analysis, of, 'T', cell, function, in, two, siblings, with, novel, 'ICOS', deficiency])]). relacion([sujeto(['Despite', normal, 'CD3/CD28-induced', proliferation, and, 'IL-2', production, in, 'vitro,', peripheral, blood, 'T', cells, in, both, patients, showed, a]), verbo([decreased]), complemento([percentage, of, 'CD4', central, and, effector, memory, 'T', cells, and, impaired, production, of, 'Th1,', 'Th2,', and, 'Th17', cytokines, upon, 'CD3/CD28', costimulation, or, 'PMA/ionophore', stimulation])]). relacion([sujeto(['The', defective, polarization, into, effector, cells, was]), verbo([associated]), complemento([with, impaired, induction, of, 'T-bet,', 'GATA3,', 'MAF,', and, retinoic, 'acid-related', orphan, nuclear, hormone, receptor, '(', 'RORC)'])]). relacion([sujeto(['Further', analysis, of, the, patients, demonstrated]), verbo([increased]), complemento([induction, of, receptor, activator, of, 'NF-kappaB', ligand, '(', 'RANKL),', lack, of, 'IFN-gamma', 'response,', and, loss, of, 'Itch', expression, upon, activation, in, the, female, 'patient,', who, had, autoimmunity])]). relacion([sujeto(['Our', study]), verbo([suggests]), complemento([that, extensive, 'T', cell, 'dysfunction,', decreased, memory, 'T', cell, 'compartment,', and, imbalance, between, effector, and, regulatory, cells, in, 'ICOS-deficient', patients, may, underlie, their, immunodeficiency, 'and/or', autoimmunity])]). relacion([sujeto(['IL-17A', is, produced, from, 'Th17', 'cells,', and, is]), verbo([involved]), complemento([in, many, autoimmune, and, inflammatory, diseases])]). relacion([sujeto(['IL-13R']), verbo([has]), complemento([not, previously, been, reported, to, be, functionally, expressed, on, 'T', 'cells;', 'however,', we, found, that, purified, 'BALB/c', 'CD4(+)', cells, polarized, to, 'Th17', with, 'TGF-beta,', 'IL-6,', and, 'IL-23', have, increased, mRNA, and, protein, expression, of, 'IL-13R', alpha1, and, mRNA, expression, of, 'IL-4R', alpha, compared, with, 'Th0,', 'Th1,', or, 'Th2', polarized, cells])]). relacion([sujeto(['The', addition, of, 'IL-13', at, 'Th17', polarization, negatively]), verbo([regulated]), complemento(['IL-17A', and, 'IL-21', 'expression,', and, reduced, the, number, of, 'CD4(+)', 'T', cells, producing, 'IL-17A'])]). relacion([sujeto(['Addition', of, 'IL-13', at, polarization]), verbo([increased]), complemento(['IL-13R', expression, in, 'wild-type', 'Th17', cells])]). relacion([sujeto(['Further,', 'IL-13', administration, during, 'Th17', polarization, 'down-regulated', retinoic, 'acid-related-gammaT,', the, transcription]), verbo([required]), complemento([for, 'Th17', 'development;', increased, 'STAT6', 'phosphorylation,', and, 'up-regulated', 'GATA3,', the, transcription, factor, activated, during, the, development, of, 'Th2', cells])]). relacion([sujeto(['This', 'IL-13-mediated', effect, was, specific, to, 'Th17', cells, as, 'IL-13', neither]), verbo([decreased]), complemento(['IFN-gamma', expression, by, 'Th1', cells, nor, affected, 'Th2', cell, production, of, 'IL-4'])]). relacion([sujeto(['Collectively,', we]), verbo([have]), complemento([shown, that, 'Th17', cells, express, a, functional, 'IL-13R', and, that, 'IL-13', negatively, regulates, 'IL-17A', and, 'IL-21', production, by, decreasing, retinoic, 'acid-related-gammaT', expression, and, while, increasing, phosphorylation, of, 'STAT6', and, 'GATA3', expression])]). relacion([sujeto(['Therefore,', therapeutic, intervention]), verbo([inhibiting]), complemento(['IL-13', production, could, have, adverse, consequences, by, 'up-regulating', 'Th17', inflammation, in, certain, disease, states])]). relacion([sujeto(['We']), verbo([find]), complemento([that, after, helminth, 'infection,', or, immunization, with, helminth, 'antigens,', reactive, lymphoid, organs, of, 4, get, 'IL-4/GFP', reporter, mice, contain, populations, of, 'IL-4/GFP-expressing', 'CD4(+)', 'T', cells, that, display, the, 'TFH', markers, 'CXCR5,', 'PD-1,', and, 'ICOS'])]). relacion([sujeto(['These', 'TFH', cells]), verbo([express]), complemento([the, canonical, 'TFH', markers, 'BCL6', and, 'IL-21,', but, also, 'GATA3,', the, master, regulator, of, 'Th2', cell, differentiation])]). relacion([sujeto(['Consistent', with, a, relationship, between, 'Th2', and, 'TFH', 'cells,', 'IL-4', protein, 'production,']), verbo([reported]), complemento([by, expression, of, huCD2, in, 'IL-4', dual, reporter, '(', 4, 'get/KN2)', 'mice,', was, a, robust, marker, of, 'TFH', cells, in, 'LNs', responding, to, helminth, antigens])]). relacion([sujeto(['Moreover,', the, majority, of, 'huCD2/IL-4-producing', 'Th', cells, were]), verbo([found]), complemento([within, 'B', cell, 'follicles,', consistent, with, their, definition, as, 'TFH', cells])]). relacion([sujeto(['The', relationship, of, 'TFH', cells, to, the, 'Th2', lineage, was, confirmed, when, 'TFH', cells, were]), verbo([found]), complemento([to, develop, from, 'CXCR5(-)', 'PD-1(-)', 'IL-4/GFP(+)', 'CD4(+)', 'T', cells, after, their, transfer, into, naive, mice, and, antigen, challenge, in, vivo])]). relacion([sujeto(['Together,', these, mechanisms]), verbo([ensure]), complemento([stable, inheritance, of, the, differentiated, fate, in, the, numerous, progeny, of, the, original, naïve, 'CD4(+)', 'T', cells])]). relacion([sujeto(['Expression', of, most, of, the, genes, disappeared, after, the, third, 'passage,', only, 'T-cell', marker, genes, were, highly]), verbo([expressed]), complemento([after, passages])]). relacion([sujeto(['Transcription', factor, 'GATA2', is]), verbo([expressed]), complemento([in, numerous, mammalian, 'tissues,', including, 'neural,', 'hematopoietic,', cardiovascular, and, urogenital, 'systems,', and, yet, it, plays, important, roles, in, the, regulation, of, 'tissue-restricted', gene, expression])]). relacion([sujeto(['The', 'Gata2', gene, itself, is, also, under, stringent, 'tissue-specific', control, and, multiple, 'cis-regulatory', domains]), verbo([have]), complemento([been, identified, in, the, 'Gata2', locus])]). relacion([sujeto(['In', this, study, we, sought, out, and, then, examined, in, detail, the, domains, that]), verbo([regulate]), complemento(['Gata2', in, the, midbrain])]). relacion([sujeto(['Importantly,', both, domains, contain, 'GATA', factor]), verbo([binding]), complemento([sites])]). relacion([sujeto(['Both', the, 2, 'H', and, 5, 'H', domains]), verbo([have]), complemento([the, independent, ability, to, activate, 'Gata2', gene, expression, in, the, midbrain, superior, 'colliculus,', whereas, the, 'distal-5H', domain, is, additionally, capable, of, activating, 'Gata2', transcription, in, the, inferior, colliculus])]). relacion([sujeto(['T', helper, 1, '(', 'Th1)-Th2', cell, balance, is, key, to, host, defense, and, its, dysregulation]), verbo([has]), complemento([pathophysiological, consequences])]). relacion([sujeto(['Lyn-deficient', mice, had, a, marked, 'basophilia,', a, constitutive, 'Th2', cell, skewing, that, was, exacerbated, upon, in, vivo, challenge, of, 'basophils,', produced, antibodies, to, a, normally, inert, 'antigen,', and, failed, to, appropriately]), verbo([respond]), complemento([to, a, 'Th1', 'cell-inducing', pathogen])]). relacion([sujeto(['The', limited, availability, of, specimens, with, complete, clinical, annotation, and, quality, biomaterial, often]), verbo([leads]), complemento([to, underpowered, studies])]). relacion([sujeto(['Tissue', microarray, 'studies,', for, 'example,', may, be, further, handicapped, by, the]), verbo([loss]), complemento([of, data, points, because, of, unevaluable, 'staining,', core, 'loss,', or, the, lack, of, tumor, in, the, histospot])]). relacion([sujeto(['The', use, of, either, lymph, node, status, or, the, four, protein, expression, levels]), verbo([provides]), complemento([similar, improvements, in, 'goodness-of-fit,', with, both, significantly, better, than, a, baseline, clinical, model])]). relacion([sujeto(['Regardless', of, 'T(H)1/T(H)2', 'theory,', 'CD4(+)', 'T', cells, of, patients, with, allergic, 'asthma,', a, typical, 'T(H)2', 'disease,', and, those, of, healthy, subjects]), verbo([expressed]), complemento([equivalent, levels, of, 'IFN-gamma,', even, though, 'T(H)2', cytokines, were, significantly, upregulated, in, asthmatic, patients])]). relacion([sujeto(['T-bet', was]), verbo([expressed]), complemento([in, 'peripheral,', but, not, cord, 'blood,', resting, naive, 'T', cells])]). relacion([sujeto(['IFN-gamma-producing', activity, was]), verbo([induced]), complemento([in, 'T(H)2-differentiated', cord, blood, 'T', cells, by, means, of, ectopic, expression, of, 'T-bet'])]). relacion([sujeto(['In', 'addition,', a, reduction, of, 'T-bet', in, peripheral, 'T', cells]), verbo([suppressed]), complemento(['IFN-gamma', production])]). relacion([sujeto(['Theiler\'s', murine, encephalomyelitis, virus, '(', 'TMEV)', infection, is, an, animal, model, of, 'MS', in, which, aberrant, immunity]), verbo([leads]), complemento([to, viral, persistence, and, subsequently, results, in, demyelination, that, resembles, 'MS'])]). relacion([sujeto(['Here,', we, examined, how, stress, during, acute, 'TMEV', infection, altered, 'virus-specific', cell]), verbo([mediated]), complemento([responses])]). relacion([sujeto(['Using', immunodominant, viral, peptides, specific, for, either, 'CD4(+)', or, 'CD8(+)', 'T', 'cells,', we]), verbo([found]), complemento([that, stress, reduced, 'IFN-gamma', producing, 'virus-specific', 'CD4(+)', and, 'CD8(+)', 'T', cells, in, the, spleen, and, 'CD8(+)', 'T', cells, 'CNS'])]). relacion([sujeto(['Cytokine', production, by, cells, isolated, from, the, 'CNS', or, spleens, following, stimulation, with, virus, or, viral, 'peptides,', indicated, that, stress]), verbo([decreased]), complemento([both, type, 1, and, type, 2, responses])]). relacion([sujeto(['Glucocorticoids', were, implicated, in, the]), verbo([decreased]), complemento(['T', cell, function, as, the, effects, of, stress, were, partially, reversed, by, concurrent, 'RU486', administration, but, mimicked, by, dexamethasone])]). relacion([sujeto(['As', 'T', cells]), verbo([mediate]), complemento([viral, clearance, in, this, 'model,', our, data, support, the, hypothesis, that, 'stress-induced', immunosuppression, may, provide, a, mechanism, for, enhanced, viral, persistence, within, the, 'CNS'])]). relacion([sujeto(['Here,', we, demonstrate, that, both, naive, and, memory, human, 'CD4(+)', 'T', cells]), verbo([express]), complemento([mRNA, for, the, 'IFN-lambda1-specific', 'receptor,', 'IL-28Ralpha,', and, are, responsive, to, 'IFN-lambda1'])]). relacion([sujeto(['Expression', of, 'Th2', cytokines, '(', 'IL-4', and, 'IL-13)', was]), verbo([suppressed]), complemento([in, naive, and, memory, 'CD4(+)', 'T', cells, by, 'IFN-lambda1,', without, affecting, their, proliferation])]). relacion([sujeto(['Further,', acquisition, of, 'IL-4Ralpha', expression, after, stimulation, was]), verbo([inhibited]), complemento([by, 'IFN-lambda1,', as, was, 'GATA3', expression])]). relacion([sujeto(['PBMC', were]), verbo([stimulated]), complemento([with, 'PHA', for, 'either,', 24, h, to, 'determine:', '(', 'a)', the, concentration, of, tocopherol, incorporated, into, the, cell, 'membrane,', '(', 'b)', cytokine, production, and, '(', 'c)', 'Th1', and, 'Th2', regulators, gene, 'expression;', or, 72, h, to, determine, the, proliferation, of, 'PBMC'])]). relacion([sujeto(['Regarding', cytokine, 'production,', vitamin, 'E', consistently]), verbo([decreases]), complemento([the, mRNA, expression, and, the, percentage, of, cells, producing, 'IL-10'])]). relacion([sujeto(['Vitamin', 'E', did, not, influence, the, production, of, 'IFN-gamma', but, the, lowest, level, of, vitamin, 'E', '(', 10, 'muM)', was, sufficient, to, maximally]), verbo([increase]), complemento([the, proportion, of, cells, producing, 'IL-2,', to, diminish, 'IL-4,', and, discreetly, increase, the, mRNA, expression, of, 'TBX21', vs])]). relacion([sujeto(['In', 'conclusion,', our, results, revealed, that, vitamin, 'E', is, able, to]), verbo([suppress]), complemento(['IL-10', production, and, to, influence, the, production, of, 'IL-2,', 'IL-4,', and, maybe, 'TBX21'])]). relacion([sujeto(['Vitamin', 'E', clearly]), verbo([has]), complemento([immunomodulatory, 'effects,', though, further, work, in, vivo, to, determine, the, physiological, nature, of, these, effects, is, warranted])]). relacion([sujeto(['Apigenin,', a, dietary, 'plant-flavonoid']), verbo([has]), complemento([shown, 'anti-inflammatory', and, anticancer, 'properties,', however, the, molecular, basis, of, this, effect, remains, to, be, elucidated])]). relacion([sujeto(['It', included, an]), verbo([increase]), complemento([in, the, number, of, eosinophils, in, bronchoalveolar, lavage, '(', 'BAL)', 'fluid,', an, increase, in, inflammatory, cell, infiltration, into, the, lung, around, blood, vessels, and, 'airways,', airway, luminal, 'narrowing,', and, the, development, of, airway, 'hyper-responsiveness', '(', 'AHR)'])]). relacion([sujeto(['Accordingly,', this, study, may]), verbo([provide]), complemento([evidence, that, apigenin, plays, a, critical, role, in, the, amelioration, of, the, pathogenetic, process, of, asthma, in, mice])]). relacion([sujeto(['These', findings]), verbo([provide]), complemento([new, insight, into, the, immunopharmacological, role, of, apigenin, in, terms, of, its, effects, in, a, murine, model, of, asthma])]). relacion([sujeto(['Sinomenine']), verbo([has]), complemento([been, used, to, treat, autoimmune, diseases, for, centuries])]). relacion([sujeto(['Increasing', recognition, of, the, importance, of, the, 'Th1/Th2', imbalance, in, nephritis]), verbo([has]), complemento([raised, the, questions, of, whether, there, is, a, 'Th1/Th2', imbalance, in, patients, with, mesangial, proliferative, nephritis, '(', 'MsPGN)', and, whether, sinomenine, can, modulate, the, 'Th1/Th2', imbalance])]). relacion([sujeto(['Results']), verbo([reveal]), complemento([that, 'PBMCs', from, 'MsPGN', patients, expressed, high, levels, of, 'T-bet', mRNA, and, low, levels, of, 'GATA-3', 'mRNA,', and, the, 'T-bet/GATA-3', ratio, in, 'MsPGN', patients, was, significantly, higher, than, that, in, healthy, donors])]). relacion([sujeto(['Meanwhile,', 'MsPGN', patients, were]), verbo([found]), complemento([to, have, simultaneously, elevated, 'IFN-gamma', values, and, decreased, 'IL-10', values])]). relacion([sujeto(['Immunohistochemistry', revealed]), verbo([increased]), complemento(['T-bet', and, decreased, 'GATA-3', expression, in, renal, tissues, from, 'MsPGN', patients])]). relacion([sujeto(['Moreover,', sinomenine, was]), verbo([found]), complemento([to, cause, a, decrease, in, 'T-bet', mRNA, 'expression,', resulting, in, a, drop, in, the, 'T-bet/GATA-3', ratio])]). relacion([sujeto(['Sinomenine', was, also]), verbo([found]), complemento([to, elicit, a, decrease, in, the, serum, levels, of, 'IFN-gamma'])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, a, shift, toward, the, 'Th1', pathway, of, 'Th', cell, activation, occurs, in, 'MsPGN', 'patients,', and, that, sinomenine, has, the, potential, to, counter, this, shift, in, the, 'Th1/Th2', balance, and, thereby, produce, therapeutic, effects])]). relacion([sujeto(['Here,', we]), verbo([provide]), complemento([a, transcriptional, regulatory, mechanism, underlying, their, balanced, production])]). relacion([sujeto(['LIM-only', protein, 'LMO4', controls, this, binary, cell, fate, choice, by]), verbo([regulating]), complemento([the, activity, of, 'V2a-', and, 'V2b-specific', 'LIM', complexes, inversely])]). relacion([sujeto(['In', the, spinal, 'cord,', 'LMO4']), verbo([induces]), complemento(['GABAergic', 'V2b-interneurons', in, collaboration, with, 'SCL', and, inhibits, 'Lhx3', from, generating, glutamatergic, 'V2a-interneuons'])]). relacion([sujeto(['In', 'LMO4;SCL', compound, mutant, 'embryos,', 'V2a-interneurons']), verbo([increase]), complemento([markedly, at, the, expense, of, 'V2b-interneurons'])]). relacion([sujeto(['This', complex]), verbo([activates]), complemento([specific, enhancers, in, 'V2b-genes', consisting, of, binding, sites, for, 'SCL', and, 'Gata2,', thereby, promoting, 'V2b-interneuron', fate])]). relacion([sujeto(['Fumigation', therapy, is, effective, in, treating, psoriasis, 'vulgaris,', its, mechanism, is, possibly, by, way, of]), verbo([modulating]), complemento([the, equilibrium, of, the, transcription, factors, 'T-bet', and, 'GATA-3', protein, expressions, in, 'PBMC,', and, rectifying, the, immune, abnormality, of, 'Th1/Th2', subsets, imbalance])]). relacion([sujeto(['Delayed', development, of, 'virus-specific', immune, response]), verbo([has]), complemento([been, observed, in, pigs, infected, with, the, porcine, reproductive, and, respiratory, syndrome, virus, '(', 'PRRSV)'])]). relacion([sujeto(['Several', studies, support, the, hypothesis, that, the, 'PRRSV', is, capable, of]), verbo([modulating]), complemento([porcine, immune, 'system,', but, the, mechanisms, involved, are, yet, to, be, defined])]). relacion([sujeto(['Our', results, showed, that, 'PRRSV-infected', 'DCs', significantly]), verbo([increased]), complemento(['Foxp3(+)CD25(+)', 'T', 'cells,', an, effect, that, was, reversible, by, 'IFN-alpha', 'treatment,', and, this, outcome, was, reproducible, using, two, distinct, 'PRRSV', strains])]). relacion([sujeto(['Analysis', of, the]), verbo([expressed]), complemento([cytokines, suggested, that, the, induction, of, 'Foxp3(+)CD25(+)', 'T', cells, is, dependent, on, 'TGF-beta', but, not, 'IL-10'])]). relacion([sujeto(['Importantly,', our, results, showed, that, the]), verbo([induced]), complemento(['Foxp3(+)CD25(+)', 'T', cells, were, able, to, suppress, the, proliferation, of, 'PHA-stimulated', 'PBMCs'])]). relacion([sujeto(['The', 'T', cells]), verbo([induced]), complemento([by, the, 'PRRSV-infected', 'DCs', fit, the, 'Foxp3(+)CD25(+)', 'T', helper, 3, '(', 'Th3)', regulatory, cell, phenotype, described, in, the, literature])]). relacion([sujeto(['In', 'conclusion,', this, data, supports, the, hypothesis, that, the, 'PRRSV', succeeds, to, establish, and, replicate, in, porcine, cells, early, 'post-infection,', in, 'part,', by]), verbo([inducing]), complemento(['Th3', regulatory, cells, as, a, mechanism, of, modulating, the, porcine, immune, system])]). relacion([sujeto(['Naturally', occurring, regulatory, 'T', cells]), verbo([have]), complemento([been, associated, with, 'long-term', allograft, survival])]). relacion([sujeto(['In', 'LTS', 'patients,', 'FOXP3', gene, expression, was]), verbo([associated]), complemento([with, 'CXCR4', gene, expression, '(', 'P=0'])]). relacion([sujeto(['Our', results]), verbo([suggest]), complemento([that, high, expression, of, 'FOXP3', and, chemokine, receptor, genes, in, 'LTS', patients, are, possible, indicators, of, a, regulatory, process, that, contributes, to, 'long-term', allograft, acceptance])]). relacion([sujeto(['Markers', that, were]), verbo([increased]), complemento([in, 'LTS', patients, were, found, to, be, decreased, in, 'ChrRx', 'patients,', suggesting, that, rejection, may, partly, be, the, result, of, a, lack, of, this, regulatory, process])]). relacion([sujeto(['Peroxisome', 'proliferator-activated', 'receptor-alpha', '(', 'PPARalpha)', agonists]), verbo([have]), complemento([been, shown, to, have, a, therapeutic, benefit, in, experimental, autoimmune, encephalomyelitis, '(', 'EAE),', an, animal, model, for, multiple, sclerosis, '(', 'MS)'])]). relacion([sujeto(['In', this, 'study,', we, investigated, the, mechanism, by, which, the, 'PPARalpha', agonist, gemfibrozil]), verbo([induces]), complemento([immune, deviation, and, protects, mice, from, 'EAE'])]). relacion([sujeto(['We', demonstrated, that, treatment, with, gemfibrozil]), verbo([increases]), complemento([expression, of, the, 'Th2', transcription, factor, 'GATA-3', and, decreases, expression, of, the, 'Th1', transcription, factor, 'T-bet', in, vitro, and, directly, ex, vivo])]). relacion([sujeto(['These', changes, correlated, with, an]), verbo([increase]), complemento([in, nuclear, 'PPARalpha', expression])]). relacion([sujeto(['PPARalpha', was, 'demonstrated,', for, the, first, 'time,', to]), verbo([regulate]), complemento([the, 'IL-4', and, 'IL-5', genes, and, to, bind, the, 'IL-4', promoter, in, the, presence, of, steroid, receptor, 'coactivator-1,', indicating, that, 'PPARalpha', can, directly, transactivate, the, 'IL-4', gene])]). relacion([sujeto(['Finally,', therapeutic, administration, of, 'PPARalpha', agonists, ameliorated, clinically, established, 'EAE,']), verbo([suggesting]), complemento([that, 'PPARalpha', agonists, may, provide, a, treatment, option, for, 'immune-mediated', inflammatory, diseases])]). relacion([sujeto(['Chronic', urticaria, '(', 'CU),', defined, as, the, recurring, incidence, of, wheals, with, or, without, angioedema, for, more, than, 6, 'weeks,', is, a, common, disorder]), verbo([associated]), complemento([with, mast, cell, 'activation,', 'degranulation,', and, histamine, release])]). relacion([sujeto(['Two', polymorphisms, of, the, 'CRTH2', 'gene,', -, 466, 'T>C', and, -, 129, 'C>A', were, genotyped, using]), verbo([primer]), complemento([extension, methods])]). relacion([sujeto(['The', luciferase, activity, was, significantly]), verbo([enhanced]), complemento([in, the, construct, containing, 'CRTH2', 466, 'C', compared, with, the, -, 466, 'T-containing', construct, '(', p, &, 'lt;', 0.001, ')'])]). relacion([sujeto(['Co-transfection', experiments, with, 'GATA-3', '(', 300, 'ng)', and, the, -, 466, 'T', and, -, 466, 'C', 'CRTH2', alleles, revealed, that, the, 'CRTH2', -, 466, 'T', allele, produced, a, greater]), verbo([increase]), complemento([in, induction, of, luciferase, activity, than, the, -, 466, 'C', allele, '(', p, &, 'lt;', 0.001, ')'])]). relacion([sujeto(['The', 'CRTH2', -, 466, 'T>C', gene, polymorphism, may, not, affect, on, the, phenotype, of, 'CU,', but, contributes, to, the]), verbo([required]), complemento([dose, of, antihistamines, in, patients, with, 'CU'])]). relacion([sujeto(['Recently,', 'PcG', gene, 'Bmi1']), verbo([has]), complemento([been, found, to, control, memory, 'Th1/Th2', cell, survival, and, 'TrxG', gene, 'MLL', is, to, control, the, maintenance, of, memory, 'Th2', cell, function, selectively])]). relacion([sujeto(['The', adjuvanticity, of, bacterial, adenylate, cyclase, toxins]), verbo([has]), complemento([been, ascribed, to, their, 'capacity,', largely, mediated, by, 'cAMP,', to, modulate, 'APC', 'activation,', resulting, in, the, expression, of, 'Th2-driving', cytokines])]). relacion([sujeto(['On', the, other, 'hand,', cAMP]), verbo([has]), complemento([been, demonstrated, to, induce, a, 'Th2', bias, when, present, during, 'T', cell, 'priming,', suggesting, that, bacterial, cAMP, elevating, toxins, may, directly, affect, the, 'Th1/Th2', balance])]). relacion([sujeto(['Here', we]), verbo([have]), complemento([investigated, the, effects, on, human, 'CD4(+)', 'T', cell, differentiation, of, two, adenylate, cyclase, 'toxins,', 'Bacillus', anthracis, edema, toxin, '(', 'ET)', and, 'Bordetella', pertussis, 'CyaA,', which, differ, in, 'structure,', mode, of, cell, 'entry,', and, subcellular, localization])]). relacion([sujeto(['We', show, that, low, concentrations, of, 'ET', and, 'CyaA,', but, not, of, their, genetically, detoxified, adenylate, cyclase, defective, 'counterparts,', potently]), verbo([promote]), complemento(['Th2', cell, differentiation, by, inducing, expression, of, the, master, 'Th2', transcription, 'factors,', 'c-maf', and, 'GATA-3'])]). relacion([sujeto(['We', also, present, evidence, that, the, 'Th2-polarizing', concentrations, of, 'ET', and, 'CyaA', selectively]), verbo([inhibit]), complemento(['TCR-dependent', activation, of, 'Akt1,', which, is, required, for, 'Th1', cell, 'differentiation,', while, enhancing, the, activation, of, two, 'TCR-signaling', 'mediators,', 'Vav1', and, 'p38,', implicated, in, 'Th2', cell, differentiation])]). relacion([sujeto(['These', results, demonstrate, 'that,', notwithstanding, their, differences, in, their, intracellular, 'localization,', which, result, in, focalized, cAMP, 'production,', both, toxins, directly, affect, the, 'Th1/Th2', balance, by, interfering, with, the, same, steps, in, 'TCR', 'signaling,', and]), verbo([suggest]), complemento([that, their, adjuvanticity, is, likely, to, result, from, their, combined, effects, on, 'APC', and, 'CD4(+)', 'T', cells])]). relacion([sujeto(['Oral', intake, of, protein]), verbo([leads]), complemento([to, tolerance, through, the, induction, of, regulatory, 'T', cells, '(', 'Tr', 'cells)', in, mesenteric, lymph, nodes, '(', 'MLNs)'])]). relacion([sujeto(['Here', we, show, that, the, inhibition, of, 'cyclooxygenase-2', '(', 'COX-2)', in, vivo]), verbo([suppressed]), complemento([oral, tolerance, and, was, associated, with, enhanced, differentiation, of, interleukin, '(', 'IL)-4-producing', 'T', cells, and, reduced, 'Foxp3(+)', 'Tr-cell', differentiation, in, 'MLN'])]). relacion([sujeto(['IL-4', was, causally, related, to]), verbo([loss]), complemento([of, tolerance, as, treatment, of, mice, with, 'anti-IL-4', antibodies, during, 'COX-2', inhibition, restored, tolerance])]). relacion([sujeto(['Dendritic', cells, '(', 'DCs)', in, the, 'MLN', differentially]), verbo([expressed]), complemento(['COX-2', and, reductionist, experiments, revealed, that, selective, inhibition, of, the, enzyme, in, these, cells, inhibited, 'Foxp3(+)', 'Tr-cell', differentiation, in, vitro])]). relacion([sujeto(['Importantly,', the, inhibition, of, 'COX-2', in, 'MLN-DC']), verbo([caused]), complemento([increased, 'GATA-3', expression, and, enhanced, 'IL-4', release, by, 'T', 'cells,', which, was, directly, related, to, impaired, 'Tr-cell', differentiation])]). relacion([sujeto(['These', data]), verbo([provide]), complemento([crucial, insights, into, the, mechanisms, driving, de, novo, 'Tr-cell', induction, and, tolerance, in, the, intestine])]). relacion([sujeto(['The', transcription, factor, 'network(s)']), verbo([required]), complemento([for, the, specific, gene, expression, signature, in, each, of, these, subtypes, is, currently, being, elucidated])]). relacion([sujeto(['Additionally,', we, discuss, modulators, of, 'FOXA1', 'function,', 'ERalpha-FOXA1-GATA3', downstream, 'targets,', and, potential, therapeutic, agents, that, may]), verbo([increase]), complemento([differentiation, through, 'FOXA1'])]). relacion([sujeto(['We', attempted, to, investigate, the, tissue, expression, of]), verbo([phosphorylated]), complemento([mammalian, target, of, rapamycin, '(', 'pmTOR)', and, infiltration, of, 'Foxp3+', 'Tregs', in, 28, nasal, polyps, and, 16, controls, by, histological, staining])]). relacion([sujeto(['Significantly']), verbo([increased]), complemento([infiltration, of, 'pmTOR+', inflammatory, cells, and, decreased, infiltration, of, 'Foxp3+CD4+', 'Tregs', into, nasal, polyps, was, 'observed,', with, an, inverse, association])]). relacion([sujeto(['In', the, tissue, culture, 'system,', we, detected, significantly, elevated, 'Foxp3', expression, and, 'IL-10', 'production,', as, well, as, an]), verbo([increased]), complemento([percentage, of, 'Foxp3+', 'Tregs', in, nasal, polyps, after, blocking, the, mTOR, signaling, pathway, with, rapamycin])]). relacion([sujeto(['Here', we, demonstrate, for, the, first, time, that, the, mTOR, signaling, pathway, is]), verbo([associated]), complemento([with, 'Foxp3+', 'Tregs', insufficiency, in, nasal, polyps])]). relacion([sujeto(['Human', 'GATA3', haploinsufficiency]), verbo([leads]), complemento([to, 'HDR', '(', 'hypoparathyroidism,', 'deafness,', and, renal, 'dysplasia)', syndrome])]). relacion([sujeto(['The', development, of, a, specific, subset, of, organs, in, which, this, transcription, factor, is]), verbo([expressed]), complemento([appears, exquisitely, sensitive, to, gene, dosage])]). relacion([sujeto(['We']), verbo([report]), complemento([on, a, 14, -, 'year-old', patient, with, symptomatic, 'hypoparathyroidism,', sensorineural, bilateral, 'deafness,', unilateral, renal, 'dysplasia,', bilateral, palpebral, 'ptosis,', and, horizontal, nystagmus])]). relacion([sujeto([108, '_109delGG)', in, exon, 2]), verbo([causing]), complemento([a, frameshift, with, a, premature, stop, codon, after, a, new, 15, -, aminoacid, sequence])]). relacion([sujeto(['Our', patient, carries, a, novel, &, 'quot;de', 'novo"', 'GATA3', 'mutation,']), verbo([providing]), complemento([further, evidence, that, 'HDR', syndrome, is, caused, by, haploinsufficiency, of, 'GATA3,', which, may, be, responsible, for, a, complex, neurologic, picture, besides, the, known, triad])]). relacion([sujeto(['Rheumatoid', arthritis, is]), verbo([associated]), complemento([with, the, infiltration, of, 'T', helper, cells, into, the, joints])]). relacion([sujeto(['Therefore,', this, study, was, aimed, at, examining, whether, the, 'Th2-specific', transcription, factor, 'GATA-3', can]), verbo([regulate]), complemento(['arthritis,', in, an, experimental, murine, 'model,', by, modulating, 'Th1', 'and/or', 'Th17', cell, polarization])]). relacion([sujeto(['Arthritis', was]), verbo([induced]), complemento([with, methylated, bovine, serum, albumin, '(', 'mBSA)', in, both, 'wild-type', and, 'CD2', 'T', 'cell-specific', 'GATA-3', '(', 'CD2-GATA-3)-transgenic', mice])]). relacion([sujeto(['Wild-type', mice, developed, severe, joint, 'inflammation,', including, massive, inflammatory, cell, infiltration, and, bone, erosion, that]), verbo([increased]), complemento([significantly, over, 'time,', reaching, maximal, arthritis, scores, at, day, 7])]). relacion([sujeto(['Expression', of, heat, shock, proteins]), verbo([has]), complemento([been, described, in, different, tissues, relevant, to, human, 'reproduction,', including, placenta])]). relacion([sujeto(['This', varying, expression, pattern]), verbo([provides]), complemento([additional, support, to, earlier, reports, of, functional, differences, between, both, proteins])]). relacion([sujeto(['CpG', island, methylation, was, ruled, out, as, the, underlying]), verbo([cause]), complemento([for, the, 'inter-individual', 'alphaB-crystallin', expression, variations])]). relacion([sujeto(['Gamma-secretase', inhibitor, '(', 'GSI)']), verbo([has]), complemento([been, used, to, effectively, block, 'Notch', 'signaling,', which, is, implicated, in, the, differentiation, and, functional, regulation, of, 'T', helper, '(', 'Th)', effector, cells])]). relacion([sujeto(['The', administration, of, 'GSI']), verbo([inhibits]), complemento([asthma, 'phenotypes,', including, eosinophilic, airway, 'inflammation,', goblet, cell, 'metaplasia,', 'methacholine-induced', airway, 'hyperresponsiveness,', and, serum, 'IgE', production])]). relacion([sujeto(['GSI', treatment, of, bronchoalveolar, lavage, cells]), verbo([stimulated]), complemento([via, 'TCR', or, 'non-TCR', pathways, led, to, a, decrease, in, 'Th2', cytokine, production, with, a, concomitant, increase, in, 'Th1', cytokine, secretion])]). relacion([sujeto(['Expression', of, 'Hes-1,', a]), verbo([target]), complemento([of, 'Notch', 'signaling,', was, 'down-regulated', in, conjunction, with, a, reduction, of, 'Notch', intracellular, domain, and, 'GATA-3', levels, after, 'GSI', treatment, of, bronchoalveolar, lavage, cells])]). relacion([sujeto(['These', data]), verbo([suggest]), complemento([that, 'GSI', directly, regulates, 'Th1', and, 'Th2', responses, in, allergic, pulmonary, inflammation, through, a, 'Notch', 'signaling-dependent', pathway, and, that, 'GSI', is, of, high, therapeutic, value, for, treating, asthma, by, inhibiting, airway, inflammatory, responses])]). relacion([sujeto(['Among', 'Tissue', kallikrein, genes, '(', 'KLKs),', 'KLK1', is, abundantly]), verbo([expressed]), complemento([in, human, skin])]). relacion([sujeto(['Although', its, putative, promoter, is, known, to]), verbo([have]), complemento([various, 'cis-elements,', they, have, not, been, functionally, tested])]). relacion([sujeto(['Luciferase', assay]), verbo([targeting]), complemento([the, 'KLK1', promoter, '(', nucleotide, -, 1153, /, +, 40, from, the, major, transcriptional, start, 'site)', was, performed, on, 'NHEK', human, keratinocyte])]). relacion([sujeto(['The', motif, search, program, failed, to]), verbo([find]), complemento([unique, binding, motifs, in, -, 428, /, -, 236, ',', whereas, both, -, 954, /, -, 855, and, -, 100, /, +, 40, had, a, unique, 'GATAs', binding, motif])]). relacion([sujeto(['Electrophoretic', mobility, shift, assay, '(', 'EMSA)', and, 'DNA', footprinting, confirmed, the]), verbo([binding]), complemento([of, 'NHEK', nuclear, protein, to, these, motifs, that, were, supershifted, by, 'anti-GATA3', antibody])]). relacion([sujeto(['Moreover,', introduction, of, 'GATA3', into, fibroblastic, 'NIH3T3', cells]), verbo([enhanced]), complemento([the, activity, of, 'KLK1', promoter, containing, -, 954, /, +, 40, ',', while, that, of, 'GATA3', dominant, negative, mutant, to, 'NHEK', cells, impaired, the, same, 'promoter\'s', activity])]). relacion([sujeto(['Thus,', 'GATA3', was]), verbo([found]), complemento([to, bind, the, site, located, at, -, 954, /, -, 855, and, to, be, a, key, regulator, of, abundant, 'KLK1', expression, in, human, keratinocyte])]). relacion([sujeto(['The', murine, model, of, asthma, was]), verbo([induced]), complemento([by, 'OVA'])]). relacion([sujeto(['Ma', 'Xing', 'Shi', 'Gan', decoction, may]), verbo([modulate]), complemento(['Thl/Th2', balance, by, suppressing, the, gene, expression, of, 'GATA-3', and, 'STAT-6', in, vivo])]). relacion([sujeto(['There', is, recent, evidence, that, 'galectin-3']), verbo([participates]), complemento([in, immunity, to, 'infections,', mostly, by, tuning, cytokine, production])]). relacion([sujeto(['The', intermediate, resistance, to, the, fungal, infection, presented, by, 'C57BL/6', 'mice,']), verbo([associated]), complemento([with, the, development, of, a, mixed, type, of, 'immunity,', was, replaced, with, susceptibility, to, infection, and, a, 'Th2-polarized', immune, 'response,', in, 'galectin-3-deficient', '(', 'gal3(-/-))', mice])]). relacion([sujeto(['Such', a, response, was]), verbo([associated]), complemento([with, defective, inflammatory, and, delayed, type, hypersensitivity, '(', 'DTH)', 'reactions,', high, 'IL-4', and, 'GATA-3', expression, and, low, nitric, oxide, production, in, the, organs, of, infected, animals])]). relacion([sujeto(['Hematopoiesis', is, a, carefully, controlled, process, that, is]), verbo([regulated]), complemento([by, complex, networks, of, transcription, factors, that, 'are,', in, 'part,', controlled, by, signals, resulting, from, ligand, binding, to, 'cell-surface', receptors])]). relacion([sujeto(['To', further, understand, 'hematopoiesis,', we]), verbo([have]), complemento([compared, gene, expression, profiles, of, human, 'erythroblasts,', 'megakaryocytes,', 'B', 'cells,', cytotoxic, and, helper, 'T', 'cells,', natural, killer, 'cells,', 'granulocytes,', and, monocytes, using, whole, genome, microarrays])]). relacion([sujeto(['In', 'addition,', we]), verbo([have]), complemento([identified, novel, coexpression, patterns, for, key, transcription, factors, involved, in, hematopoiesis, '(', 'eg,', 'GATA3-GFI1', and, 'GATA2-KLF1)'])]). relacion([sujeto(['This', study, represents, the, most, comprehensive, analysis, of, gene, expression, in, hematopoietic, cells, to, date, and]), verbo([has]), complemento([identified, genes, that, play, key, roles, in, lineage, commitment, and, cell, function])]). relacion([sujeto(['The', hypothesis, of, this, study, was, that, such, a, module, could, be, 'a)']), verbo([found]), complemento([and, validated, in, allergic, disease, and, 'b)', used, to, find, and, validate, one, ore, more, novel, 'disease-associated', genes])]). relacion([sujeto(['This']), verbo([led]), complemento([to, the, identification, of, an, experimentally, validated, reference, gene, that, was, used, to, construct, a, module, of, 'co-expressed', and, interacting, genes])]). relacion([sujeto(['The', expression, levels, of, 'IL7R', in, allergen, challenged, 'CD4+', cells]), verbo([decreased]), complemento([following, challenge, but, increased, after, treatment])]). relacion([sujeto(['This']), verbo([suggested]), complemento([an, inhibitory, 'role,', which, was, confirmed, by, functional, studies])]). relacion([sujeto(['We', propose, that, a, 'module-based', analytical, strategy, is, generally, applicable, to]), verbo([find]), complemento([novel, genes, in, complex, diseases])]). relacion([sujeto(['By', microarray, expression, analysis, '(', 'Affymetrix', 'HU133A)', important, players, in, the, noradrenalin, biosynthesis, pathway, '(', 'DBH,', 'DDC,', 'GATA2,', 'GATA3,', 'PHOX2A,', 'PHOX2B,', 'SLC6A2', 'SLC18A1', and, 'TH)', were]), verbo([found]), complemento([to, be, among, the, top, ranked, genes, in, showing, lower, expression, in, unfavorable, 'NB', tumor, types, as, compared, to, favorable, ones])]). relacion([sujeto(['PHOX2A,', a, downstream]), verbo([target]), complemento([of, 'Phox2b,', was, found, to, be, the, sixth, ranked, gene, from, the, microarray, gene, list])]). relacion([sujeto(['However,', no, critical, changes, were]), verbo([found]), complemento([that, could, support, its, role, in, tumor, development, or, progression])]). relacion([sujeto(['Overall,', the, findings, in, this, study, either]), verbo([suggest]), complemento([that, expression, of, this, pathway, could, be, a, predictive, differentiation, marker, of, 'NB', 'tumors,', or, our, results, could, also, imply, that, the, noradrenalin, biosynthesis, pathway, is, involved, in, tumor, pathogenesis])]). relacion([sujeto(['Based', on, potential, transcription, factor]), verbo([binding]), complemento([sites, in, their, putative, 'promoters,', we, hypothesized, that, expression, of, 'APOBEC3G', and, 'APOBEC3F', would, vary, with, 'T', helper, lymphocyte, differentiation])]). relacion([sujeto(['T', cell, receptor, stimulation, further]), verbo([increased]), complemento(['APOBEC3G', and, 'APOBEC3F', expression, in, 'Tbet-', and, 'control-transduced,', but, not, in, 'GATA3-transduced,', cells])]). relacion([sujeto(['HIV-1', produced, from, 'Th1', cells, had, more, virion, 'APOBEC3G,', and]), verbo([decreased]), complemento(['infectivity,', compared, to, virions, produced, from, 'Th2', cells])]). relacion([sujeto(['Over-expression', of, 'APOBEC3G', in, 'Th2', cells]), verbo([decreased]), complemento([the, infectivity, of, virions, produced, from, 'Th2', 'cells,', and, reduction, of, 'APOBEC3G', in, 'Th1', cells, increased, infectivity, of, virions, produced, from, 'Th1', 'cells,', consistent, with, a, causal, role, for, 'APOBEC3G', in, the, infectivity, difference])]). relacion([sujeto(['These', results, indicate, that, 'APOBEC3G', and, 'APOBEC3F', levels, vary, physiologically, during, 'CD4+', 'T', lymphocyte, 'differentiation,', that, 'interferon-gamma', contributes, to, this, 'modulation,', and, that, this, physiological, regulation, can]), verbo([cause]), complemento([changes, in, infectivity, of, progeny, 'virions,', even, in, the, presence, of, 'HIV-1', vif])]). relacion([sujeto(['Heterozygous', somatic, mutations, of, the, transcription, 'factor,', 'GATA-3,']), verbo([have]), complemento([recently, been, reported, in, approximately, 5, '%', breast, of, tumors, unselected, for, family, history])]). relacion([sujeto(['We', sequenced, the, 'GATA-3', gene, in, 55, breast, tumors, from, women, with, familial, breast, 'cancer,', and]), verbo([found]), complemento([seven, heterozygous, somatic, 'mutations,', all, in, 'non-BRCA1/2', cases, in, which, the, frequency, was, 22, '%'])]). relacion([sujeto(['In', 'contrast,', we]), verbo([found]), complemento([mutations, of, 'GATA-3', in, only, 4, '%', of, 81, sporadic, tumors, analysed])]). relacion([sujeto(['No', statistic, difference, in, 'DC1/DC2', ratio, was]), verbo([found]), complemento([between, untreated, and, recovered, patients, '(', 'P', &, 'lt;', 0.05, ')'])]). relacion([sujeto(['Recent', research]), verbo([has]), complemento([uncovered, complex, transcription, factor, networks, that, control, the, processes, of, 'T-cell', development, and, differentiation])]). relacion([sujeto(['RUNX', '(', 'runt-related', transcription, 'factor)', proteins, are, among, the, many, factors, that]), verbo([have]), complemento([crucial, roles, in, these, networks])]). relacion([sujeto(['In', this, 'Review,', we, examine, the, mechanisms, by, which, 'RUNX', complexes]), verbo([act]), complemento([together, with, other, transcription, 'factors,', such, as, 'Th-POK', '(', 'T-helper-inducing', 'POZ/Kruppel-like', 'factor)', and, 'GATA-binding', protein, 3, '(', 'GATA3)', in, determining, the, 'CD4/CD8', lineage, choice, of, developing, thymocytes])]). relacion([sujeto(['In', 'addition,', we, discuss, evidence, indicating, that, 'RUNX', complexes, are, also]), verbo([involved]), complemento([in, the, differentiation, of, effector, 'T-cell', subsets, and, that, the, molecular, mechanisms, by, which, 'RUNX', proteins, regulate, 'T-cell', fate, decisions, are, conserved, between, the, thymus, and, periphery])]). relacion([sujeto(['BMP', antagonists, can]), verbo([induce]), complemento([neural, plate, border, markers, in, both, ventral, 'Xenopus', epidermis, and, 'non-neural', chick, epiblast])]). relacion([sujeto(['However,', 'BMP', antagonism, can, only, neuralize, ectodermal, cells, when, the, 'BMP-inhibited', cells, form, a, continuous, trail, connecting, them, to, the, neural, plate, or, its, 'border,']), verbo([suggesting]), complemento([that, homeogenetic, neuralizing, factors, can, only, travel, between, 'BMP-inhibited', cells])]). relacion([sujeto(['Furthermore,', chick, explants, isolated, from, embryonic, epiblast, behave, like, 'Xenopus', animal, caps, and]), verbo([express]), complemento([border, markers])]). relacion([sujeto(['Prior', studies, demonstrate, that, 'SAP']), verbo([enhances]), complemento(['TCR-induced', activation, of, 'NF-kappaB', in, 'CD4(+)', 'T', cells])]). relacion([sujeto(['Because', 'NF-kappaB', is]), verbo([required]), complemento([for, 'NKT', cell, 'development,', 'SAP', might, promote, the, ontogeny, of, this, lineage, by, signaling, to, 'NF-kappaB'])]). relacion([sujeto(['In', this, 'study,', we, demonstrate, that, forced, expression, of, the, 'NF-kappaB']), verbo([target]), complemento(['gene,', 'Bcl-x(L),', or, inhibitory, 'NF-kappaB', kinase, 'beta,', a, catalytic, subunit, of, the, 'IkappaB', kinase, complex, essential, for, 'NF-kappaB', 'activation,', fails, to, restore, 'NKT', cell, development, in, 'sap(-/-)', 'mice,', suggesting, that, 'SAP', mediates, 'NKT', cell, development, independently, of, 'NF-kappaB'])]). relacion([sujeto(['To', examine, the, role, of, 'SAP', in, 'NKT', cell, 'function,', we, generated, 'NKT', cells, in, 'sap(-/-)', mice, by]), verbo([expressing]), complemento([a, transgene, encoding, the, 'Valpha14', 'Jalpha18', component, of, the, invariant, 'TCR'])]). relacion([sujeto(['These', cells]), verbo([bound]), complemento(['alpha-galactosylceramide-loaded', 'CD1d', 'tetramers,', but, exhibited, a, very, immature, 'CD24(+)NK1'])]). relacion([sujeto(['The', reduction, in, cytokine, production, correlated, with, the, near, absence, of, 'GATA-3', and, 'T-bet,', key, transcription, factors]), verbo([regulating]), complemento([cytokine, expression, and, maturation, of, 'NKT', cells])]). relacion([sujeto(['Collectively,', these, data]), verbo([suggest]), complemento([that, by, promoting, 'GATA-3', and, 'T-bet', 'expression,', 'SAP', exerts, control, over, 'NKT', cell, development, and, mature, 'NKT', cell, cytokine, production])]). relacion([sujeto(['Many', advances, in, our, understanding, of, the, molecules, that]), verbo([regulate]), complemento([the, 'development,', differentiation, and, function, of, 'T', cells, have, been, made, over, the, past, few, years])]). relacion([sujeto(['Although', the, main, function, of, 'GATA3', is, to]), verbo([act]), complemento([as, a, master, transcription, factor, for, the, differentiation, of, 'T', helper, 2, '(', 'T(H)2)', 'cells,', new, research, has, helped, to, uncover, crucial, functions, of, 'GATA3', in, 'T', cells, that, go, beyond, 'T(H)2-cell', differentiation, and, that, are, important, at, earlier, stages, of, haematopoietic, and, 'lymphoid-cell', development])]). relacion([sujeto(['There', is, growing, evidence, that, 'hypoxia-inducible', transcription, factors, are]), verbo([involved]), complemento([in, the, pathophysiology, of, asthma])]). relacion([sujeto(['Hypoxia-inducible', 'factor-1alpha', '(', 'HIF-1alpha)', in, particular, controls, the, expression, of, many, hypoxia]), verbo([regulated]), complemento(['genes,', but, whether, 'HIF-1alpha', directly, contributes, to, 'allergen-driven', immune, responses, is, not, known])]). relacion([sujeto(['Spleen', 'CD4+', 'T', cells, were]), verbo([stimulated]), complemento([with, 'anti-CD3', plus, 'anti-CD28', antibodies, and, cytokine, secretion, was, measured, in, vitro])]). relacion([sujeto(['Interferon-gamma', secretion, was, significantly, higher, in, 'anti-CD3', plus, 'anti-CD28']), verbo([stimulated]), complemento(['CD4+', 'T', cells, obtained, from, 'HIF-1alpha(+/-)', mice, compared, to, 'wild-type', controls])]). relacion([sujeto(['HIF-1alpha(+/-)', mice, were, protected, from, lung, eosinophilia, 72, h, after, allergen, 'challenge,', in, association, with]), verbo([enhanced]), complemento([secretion, of, 'interferon-gamma', in, recall, responses, of, splenocytes])]). relacion([sujeto(['Chromatin', immunoprecipitation, analysis, revealed, multiple, 'CTCF']), verbo([binding]), complemento([sites, in, the, 'Th2', cytokine, locus])]). relacion([sujeto(['We']), verbo([found]), complemento([that, in, 'CTCF-deficient', 'Th2', polarization, 'cultures,', transcription, of, 'IL-4,', 'IL-5,', and, 'IL-13', was, strongly, reduced])]). relacion([sujeto(['In', 'CTCF-deficient', 'Th2', 'cultures,', cells, were, polarized, toward, the, 'Th2', 'lineage,', as, substantiated, by, induction, of, the, key, transcriptional, regulators, 'GATA3', and, special, 'AT-rich']), verbo([binding]), complemento([protein, 1, '(', 'SATB1)', and, 'down-regulation', of, 'T-bet'])]). relacion([sujeto(['Ikaros,', a, hematopoietic, transcription, 'factor,']), verbo([has]), complemento([well, defined, effects, on, early, lymphocyte, development, in, the, bone, marrow, and, thymus])]). relacion([sujeto(['CD4+', 'T', cells, from, naive, 'Ikaros(null)', mice, cultured, under, 'Th2-skewing', conditions]), verbo([express]), complemento([the, 'Th1', cytokine, 'IFN-gamma', and, have, reduced, 'IL-4,', 'IL-5,', and, 'IL-13', expression])]). relacion([sujeto(['Ikaros', directly]), verbo([associates]), complemento([with, several, 'Th2', locus, regulatory, regions, in, naive, 'CD4+', 'T', cells])]). relacion([sujeto(['The']), verbo([decreased]), complemento([ability, to, express, 'Th2', cytokines, in, 'Ikaros(null)T', cells, corresponds, with, histone, 3, hypoacetylation, across, the, 'Th2', cytokine, locus, as, well, as, decreased, 'GATA3', and, cMaf, and, increased, 'T-bet', and, 'STAT1', expression])]). relacion([sujeto(['These', data, support, a, model, whereby, 'Ikaros', directly]), verbo([activates]), complemento(['Th2', gene, expression, by, promoting, local, chromatin, accessibility, during, 'CD4+', 'T', cell, differentiation, and, also, acts, indirectly, to, regulate, expression, of, 'Th2-', and, 'Th1-specific', transcription, factors])]). relacion([sujeto(['Glucocorticoid', '(', 'GC)', immunosuppression, and, 'anti-inflammatory', action]), verbo([involve]), complemento([the, regulation, of, several, transcription, factors, '(', 'TFs)'])]). relacion([sujeto(['GCs']), verbo([inhibit]), complemento([the, acute, production, of, 'T-helper', '(', 'Th)', 1, and, 'Th2', cytokines, but, ultimately, favor, a, shift, toward, 'Th2', phenotype])]). relacion([sujeto(['GCs']), verbo([inhibit]), complemento([the, transcriptional, activity, of, 'T-bet', 'Th1', 'TF', by, a, transrepression, mechanism])]). relacion([sujeto(['We']), verbo([found]), complemento([that, 'GCs', inhibit, 'GATA-3', transcriptional, activity])]). relacion([sujeto(['We', demonstrate, that, this, mechanism, does, not]), verbo([involve]), complemento([physical, interaction, between, the, glucocorticoid, receptor, '(', 'GR)', and, 'GATA-3', or, reduction, of, 'GATA-3', binding, to, 'DNA,', as, described, previously, for, 'T-bet'])]). relacion([sujeto(['Instead,', 'GCs']), verbo([inhibit]), complemento(['GATA-3', activity, by, inhibition, of, p38, 'mitogen-activated', protein, kinase, induced, 'GATA-3', phosphorylation])]). relacion([sujeto(['GCs', also]), verbo([inhibit]), complemento(['GATA-3', mRNA, and, protein, expression])]). relacion([sujeto(['In', view, of, the, crucial, role, of, 'GATA-3', in, 'T-cell', differentiation, and, 'inflammation,', we, propose, that, the, mechanism, of, 'GATA-3', inhibition, compared, with, that, in, 'T-bet', may]), verbo([have]), complemento([relevant, implications, in, understanding, and, modulating, the, 'anti-inflammatory', and, 'Th-regulatory', properties, of, 'GCs'])]). relacion([sujeto(['Periapical', chronic, lesion, formation]), verbo([involves]), complemento([activation, of, the, immune, response, and, alveolar, bone, resorption, around, the, tooth, apex])]). relacion([sujeto(['However,', the, overall, roles, of, 'T', helper, type, 1, '(', 'Th1),', 'Th2,', and, 'T-regulatory', cell, '(', 'Treg)', responses, and, osteoclast, regulatory, factors, in, periapical, cysts, and, granulomas]), verbo([have]), complemento([not, been, fully, determined])]). relacion([sujeto(['This', study, aimed, to, investigate, whether, different, forms, of, apical, 'periodontitis,', namely, cysts, and, 'granulomas,', show, different, balances, of, 'Th1,', 'Th2', 'regulators,', 'Treg', 'markers,', and, factors]), verbo([involved]), complemento([in, osteoclast, chemotaxis, and, activation])]). relacion([sujeto(['The', concomitant, expression, of, 'Treg', cell, markers]), verbo([suggests]), complemento([a, possible, suppression, of, the, 'Th1', response, in, granulomas])]). relacion([sujeto(['The', mechanisms, of, periradicular, lesion, development, are, still, not, fully, understood, but, the, imbalance, of, immune, and, osteoclastic, cell, activity, in, cysts, and, granulomas, seems, to, be, critically]), verbo([regulated]), complemento([by, 'Treg', cells])]). relacion([sujeto(['Central', to, this, 'process,', 'GDNF', secreted, from, the, metanephric, mesenchyme]), verbo([induces]), complemento([ureter, budding, by, activating, the, 'Ret', receptor, expressed, in, the, nephric, duct, epithelium])]). relacion([sujeto(['A', failure, to]), verbo([regulate]), complemento([this, pathway, is, believed, to, be, responsible, for, a, large, proportion, of, the, developmental, anomalies, affecting, the, urogenital, system])]). relacion([sujeto(['Here,', we, show, that, the, nephric, 'duct-specific', inactivation, of, the, transcription, factor, gene, 'Gata3']), verbo([leads]), complemento([to, massive, ectopic, ureter, budding])]). relacion([sujeto(['We', show, that, 'Gata3', inactivation]), verbo([causes]), complemento([premature, nephric, duct, cell, differentiation, and, loss, of, 'Ret', receptor, gene, expression])]). relacion([sujeto(['These', changes, ultimately, affect, nephric, duct, epithelium, 'homeostasis,']), verbo([leading]), complemento([to, ectopic, budding, of, interspersed, cells, still, expressing, the, 'Ret', receptor])]). relacion([sujeto(['Importantly,', the, formation, of, these, ectopic, buds]), verbo([requires]), complemento([both, 'GDNF/Ret', and, 'Fgf', signaling, activities])]). relacion([sujeto(['We', further, identify, 'Gata3', as, a, central, mediator, of, 'beta-catenin', function, in, the, nephric, duct, and, demonstrate, that, the, 'beta-catenin/Gata3', pathway]), verbo([prevents]), complemento([premature, cell, differentiation, independently, of, its, role, in, regulating, 'Ret', expression])]). relacion([sujeto(['Together,', these, results, establish, a, genetic, cascade, in, which, 'Gata3']), verbo([acts]), complemento([downstream, of, 'beta-catenin,', but, upstream, of, 'Ret,', to, prevent, ectopic, ureter, budding, and, premature, cell, differentiation, in, the, nephric, duct])]). relacion([sujeto(['GATA2', and, 'GATA3']), verbo([have]), complemento([been, implicated, in, the, regulation, of, 'trophoblast-specific', genes])]). relacion([sujeto(['In', this, 'study,', we, demonstrate, that, 'Gata2', is, transcriptionally]), verbo([induced]), complemento([during, trophoblast, giant, 'cell-specific', differentiation])]). relacion([sujeto(['Transcriptional', induction, is]), verbo([associated]), complemento([with, displacement, of, 'GATA3-dependent', nucleoprotein, complexes, by, 'GATA2-dependent', nucleoprotein, complexes, at, two, regulatory, 'regions,', the, -, 3.9, -, and, +, 9.5, -, kb, 'regions,', of, the, mouse, 'Gata2', locus])]). relacion([sujeto(['We', also]), verbo([found]), complemento([that, knockdown, of, 'GATA3', by, 'RNA', interference, induces, 'GATA2', in, undifferentiated, trophoblast, cells])]). relacion([sujeto(['Interestingly,', three, other, known, 'GATA', 'motif-dependent', 'Gata2', regulatory, 'elements,', the, -, 1.8, -, ',', -, 2.8, -, ',', and, -, 77, -, kb, 'regions,', which, are, important, to]), verbo([regulate]), complemento(['Gata2', in, hematopoietic, cells, are, not, occupied, by, 'GATA', factors, in, trophoblast, cells])]). relacion([sujeto(['Our', results, indicate, that, 'GATA3', directly, represses, 'Gata2', in, undifferentiated, trophoblast, 'cells,', and, a, switch, in, chromatin, occupancy, between, 'GATA3', and, 'GATA2', '(', 'GATA3/GATA2', 'switch)']), verbo([induces]), complemento([transcription, during, trophoblast, differentiation])]). relacion([sujeto(['Choice', of, a, 'T', lymphoid, fate, by, hematopoietic, progenitor, cells, depends, on, sustained, 'Notch-Delta', signaling, combined, with, tightly]), verbo([regulated]), complemento([activities, of, multiple, transcription, factors])]). relacion([sujeto(['To', dissect, the, regulatory, network, connections, that]), verbo([mediate]), complemento([this, 'process,', we, have, used, 'high-resolution', analysis, of, regulatory, gene, expression, trajectories, from, the, beginning, to, the, end, of, 'specification,', tests, of, the, 'short-term', 'Notch', dependence, of, these, gene, expression, 'changes,', and, analyses, of, the, effects, of, overexpression, of, two, essential, transcription, 'factors,', namely, 'PU'])]). relacion([sujeto(['Quantitative', expression, measurements, of, &, 'gt;50', transcription, factor, and, marker, genes]), verbo([have]), complemento([been, used, to, derive, the, principal, components, of, regulatory, change, through, which, 'T', cell, precursors, progress, from, primitive, multipotency, to, 'T', lineage, commitment])]). relacion([sujeto(['Our', analyses]), verbo([reveal]), complemento([separate, contributions, of, 'Notch', 'signaling,', 'GATA-3', 'activity,', and, 'down-regulation', of, 'PU'])]). relacion([sujeto(['org),', the, results]), verbo([have]), complemento([been, assembled, into, a, draft, gene, regulatory, network, for, the, specification, of, 'T', cell, precursors, and, the, choice, of, 'T', as, opposed, to, 'myeloid/dendritic', or, 'mast-cell', fates])]). relacion([sujeto([1, as, proposed, 'elsewhere,', but]), verbo([requires]), complemento([additional, functions, that, remain, unidentified])]). relacion([sujeto(['To', further, investigate, the, similarities, '(', or, 'dissimilarities)', between, female, genital, tract, transitional, proliferations, and, bladder, 'urothelium,', we, evaluated, the, expression, of, 'S100P', and, 'GATA3,', 2, proteins, that, we, previously]), verbo([found]), complemento([to, be, strongly, expressed, in, bladder, urothelial, 'tumors,', in, 25, benign, ovarian, 'Brenner', 'tumors,', 19, 'Walthard', cell, nests, '(', 17, tubal, and, 2, ovarian, 'hilus),', 1, mature, teratoma, with, a, benign, urothelial, 'proliferation,', 2, proliferating, '(', 'borderline)', ovarian, 'Brenner', 'tumors,', 1, malignant, 'Brenner', 'tumor,', and, 12, ovarian, transitional, cell, carcinomas, '(', 'TCC)'])]). relacion([sujeto(['The', indeterminate, phenotype, seen, in, 'Walthard', nests, and, ovarian, 'TCC']), verbo([suggests]), complemento([that, these, proliferations, may, represent, an, incomplete, or, alternate, form, of, differentiation])]). relacion([sujeto(['Using', 'tissue-specific', inactivation, and, ectopic, 'expression,', we, show, that, 'Gata2']), verbo([regulates]), complemento(['GABAergic', neuron, development, in, the, mouse, 'midbrain,', but, not, in, rhombomere, 1, ',', where, it, is, needed, in, the, serotonergic, lineage])]). relacion([sujeto(['Without', 'Gata2,', all, the, precursors, in, the, embryonic, midbrain, fail, to]), verbo([activate]), complemento(['GABAergic', 'neuron-specific', gene, expression, and, instead, switch, to, a, glutamatergic, phenotype])]). relacion([sujeto(['Surprisingly,', this, fate, switch, is, also, observed, throughout, the, neonatal, 'midbrain,', except, for, the, 'GABAergic', neurons, located, in, the, ventral, dopaminergic, 'nuclei,']), verbo([suggesting]), complemento([a, distinct, developmental, pathway, for, these, neurons])]). relacion([sujeto(['GATA3', is, a, transcription, factor, closely]), verbo([associated]), complemento([with, estrogen, receptor, alpha, in, breast, 'carcinoma,', with, a, potential, prognostic, utility])]). relacion([sujeto(['We']), verbo([found]), complemento([no, statistically, significant, differences, in, recurrence, or, survival, rates, between, 'GATA3-positive', and, 'GATA3-negative', tumors])]). relacion([sujeto(['GATA-binding', protein, 3, '(', 'GATA3)', is, a, transcription, factor, that, is, crucial, to, mammary, gland, morphogenesis, and, differentiation, of, progenitor, 'cells,', and]), verbo([has]), complemento([been, suggested, to, have, a, tumor, suppressor, function])]). relacion([sujeto(['The', rs570613, single, nucleotide, polymorphism, '(', 'SNP)', in, intron, 4, of, 'GATA3', was, previously]), verbo([found]), complemento([to, be, associated, with, a, reduction, in, breast, cancer, risk, in, the, 'Cancer', 'Genetic', 'Markers', of, 'Susceptibility', project, and, in, pooled, analysis, of, two, 'case-control', studies, from, 'Norway', and, 'Poland', '(', 'P', '(', 'trend)', =, 0.004, ')', ',', with, some, evidence, for, a, stronger, association, with, estrogen, receptor, '(', 'ER)', negative, tumours, '[', 'Garcia-Closas', 'M', et, al])]). relacion([sujeto(['We']), verbo([found]), complemento([no, association, between, this, 'SNP', and, breast, cancer, risk, in, 'BCAC', cases, overall, '(', 'OR(per-allele)', =, 1.0, ',', 95, '%', 'CI', 0.94, -, 1.05, ')', ',', in, 'ER', negative, 'BCAC', cases, '(', 'OR(per-allele)', =, 1.02, ',', 95, '%', 'CI', 0.91, -, 1.13, ')', ',', in, 'BRCA1', mutation, carriers, 'RR(per-allele)', =, 0.99, ',', 95, '%', 'CI', 0.9, -, 1.09, ')', or, 'BRCA2', mutation, carriers, '(', 'RR(per-allele)', =, 0.93, ',', 95, '%', 'CI', 0.8, -, 1.07, ')'])]). relacion([sujeto(['We', conclude, that, there, is, no, evidence, that, either, 'GATA3', 'rs570613,', or, any, variant, in, strong, linkage, disequilibrium, with, 'it,', is]), verbo([associated]), complemento([with, breast, cancer, risk, in, women])]). relacion([sujeto(['The', 'CD4+CD25+Foxp3+Treg', proportion, in, splenocytes, significantly]), verbo([decreased]), complemento([during, the, acute, infection, stage, and, to, the, lowest, level, of, '(', 1.46, +, /, -, 0.27, ')', '%', at, day, 28, ',', significantly, lower, than, that, of, the, mock, infection, group, '[', '(', 2.78, +, /, -, 0.29, ')', '%', ',', 'P<0'])]). relacion([sujeto([5, ']', ;, then, obviously]), verbo([increased]), complemento([in, the, chronic, infection, 'stage,', increased, to, '(', 4.51, +, /, -, 0.24, ')', '%', at, day, 60, ',', significantly, higher, than, that, of, the, mock, infection, group, '[', '(', 2.69, +, /, -, 0.12, ')', '%', ',', 'P<0'])]). relacion([sujeto([5, ']', ',', and, continued, to]), verbo([increase]), complemento([still])]). relacion([sujeto(['The', protein, level, '(', 'K', 'value)', of, 'T-bet', of, the, 'MCMV', infection, group, peaked, to, the, level, of, '(', 0.618, +, /, -, 0.053, ')', on, day, 3, ',', obviously, higher, than, that, of, the, mock, infected, group, '[', '(', 0.205, +, /, -, 0.026, ')', ']', ',', then]), verbo([decreased]), complemento([to, the, level, similar, to, that, of, the, mock, infection, group, on, day, 28, ',', and, was, obviously, lower, than, that, of, the, mock, infection, group, on, day, 75])]). relacion([sujeto(['Whereas', the, protein, level, of, 'GATA-3', of, the, 'MCMV', group]), verbo([increased]), complemento([to, '(', 0.836, +, /, -, 0.061, ')', on, day, 3, ',', markedly, higher, than, that, of, the, mock, infection, group, '(', 0.398, +, /, -, 0.022, ')', ',', peaked, on, day, 7, ',', then, gradually, 'decreased,', and, remained, at, the, levels, similar, to, those, of, the, mock, infection, group, from, day, 75, to, day, 120])]). relacion([sujeto(['But', during, the, chronic, infection, 'stage,', 'MCMV']), verbo([induces]), complemento([a, marked, proliferation, and, activation, of, 'Treg', cells, which, further, inhibit, the, 'Th1', and, 'Th2', 'reactions,', especially, 'Th1', response])]). relacion([sujeto(['To', evaluate, the, balance, of, interleukin, 'IL18', and, its, endogenous, antagonist, 'IL18']), verbo([binding]), complemento([protein, '(', 'IL18BP)', in, patients, with, idiopathic, thrombocytopenic, purpura, '(', 'ITP),', plasma, 'IL18,', 'IL18BP,', interferon, gamma, '(', 'IFNG)', and, 'IL4', 'levels,', as, well, as, platelet, counts, were, measured, in, patients, with, active, 'ITP', '(', n, =, 23, ')', ',', 'ITP', in, remission, '(', n, =, 21, ')', and, in, healthy, subjects, '(', n, =, 24, ')', by, enzyme, linked, immunosorbent, assay, '(', 'ELISA)'])]). relacion([sujeto(['The', results, showed, that, 'IL18', and, 'IFNG', protein, and, mRNA, levels, were, significantly]), verbo([increased]), complemento([in, patients, with, active, 'ITP', than, in, control, 'subjects,', but, that, 'IL18BP', were, not, significantly, elevated, in, 'ITP', 'patients,', which, resulted, in, an, elevated, ratio, of, 'IL18/IL18BP', in, patients, with, active, disease])]). relacion([sujeto(['The', elevated, levels, of, 'IL18/IL18BP', in, plasma, during, active, stages, of, disease]), verbo([suggest]), complemento([a, possible, role, in, the, pathogenesis, and, course, of, 'ITP'])]). relacion([sujeto(['Systemic', administration, of, 'cytosine-guanine', '(', 'CpG)', oligodeoxynucleotides]), verbo([provides]), complemento([neuroprotection, against, subsequent, cerebral, ischemic, injury])]). relacion([sujeto(['CpG', preconditioning]), verbo([induced]), complemento([a, novel, response, to, middle, cerebral, artery, occlusion, within, circulating, leukocytes, that, was, dominated, by, natural, killer, 'cell-associated', genes, and, the, 'GATA-3', transcriptional, regulatory, element])]). relacion([sujeto(['Preconditioning', also]), verbo([caused]), complemento([a, novel, brain, response, to, stroke, that, was, dominated, by, 'Type', 'I', 'interferon,', 'interferon-associated', 'genes,', and, transcriptional, regulatory, elements])]). relacion([sujeto(['Quercetin', is]), verbo([found]), complemento([to, be, the, most, active, of, the, flavonoids, in, studies, and, many, medicinal, plants, owe, much, of, their, activity, to, their, high, 'Quercetin', content])]). relacion([sujeto(['Quercetin']), verbo([has]), complemento([demonstrated, significant, 'anti-inflammatory', activity, because, of, direct, inhibition, of, several, initial, processes, of, inflammation])]). relacion([sujeto(['In', this, 'study,', we]), verbo([have]), complemento([attempted, to, determine, whether, 'Quercetin', regulates, 'Th1/Th2', cytokine, 'production,', 'T-bet', and, 'GATA-3', gene, expression, in, 'OVA-induced', asthma, model, mice])]). relacion([sujeto(['Quercetin', reduced, the]), verbo([increased]), complemento([levels, of, 'IL-4,', 'Th2', cytokine, production, in, 'OVA-sensitized', and, -, challenged, mice])]). relacion([sujeto(['The', other, 'side,', it]), verbo([increased]), complemento(['IFN-gamma,', 'Th1', cytokine, production, in, 'Quercetin', administrated, mice])]). relacion([sujeto(['Accordingly,', this, study, may]), verbo([provide]), complemento([evidence, that, 'Quercetin', plays, a, critical, role, in, the, amelioration, of, the, pathogenetic, process, of, asthma, in, mice])]). relacion([sujeto(['These', findings]), verbo([provide]), complemento([new, insight, into, the, immunopharmacological, role, of, 'Quercetin', in, terms, of, its, effects, in, a, murine, model, of, 'asthma,', and, also, broaden, current, perspectives, in, our, understanding, of, the, immunopharmacological, functions, of, 'Quercetin'])]). relacion([sujeto(['Among', several, other, 'roles,', 'GATA-3']), verbo([has]), complemento([recently, been, identified, as, a, key, player, of, luminal, cell, differentiation, in, the, mammary, gland])]). relacion([sujeto(['The', majority, of, breast, cancers, arise, from, luminal, epithelial, cells, and, hence, 'GATA-3', appears, to, control, a, set, of, genes]), verbo([involved]), complemento([in, the, differentiation, and, proliferation, of, breast, cancer])]). relacion([sujeto(['The', expression, of, 'GATA-3']), verbo([has]), complemento([a, strong, association, with, the, expression, of, estrogen, 'receptor-alpha', '(', 'ER)', in, breast, 'cancer,', and, there, is, mounting, evidence, that, 'GATA-3', can, be, used, as, a, clinical, marker, to, determine, response, to, hormonal, therapy, and, to, refine, the, prognosis, of, breast, cancer, patients])]). relacion([sujeto(['We']), verbo([report]), complemento([the, case, of, 43, -, 'year-old', 'Japanese', man, with, 'PTH-deficient', hypoparathyroidism, introduced, to, an, endocrinologist, in, our, hospital])]). relacion([sujeto(['As']), verbo([he]), complemento([had, complained, of, hearing, disturbance, since, the, age, of, 20, ',', we, decided, to, investigate, the, 'GATA3', gene])]). relacion([sujeto(['The', mutation, introduces, a, premature, stop, codon, at, exon, 4, '(', 'K302X),', which, results, in, a]), verbo([loss]), complemento([of, both, zinc, finger, domains, of, the, 'GATA3', protein])]). relacion([sujeto(['However,', because, the, mutation, in, the, 'GATA3', gene]), verbo([found]), complemento([in, this, patient, is, highly, likely, to, impair, 'GATA3', 'function,', we, speculate, that, it, is, extremely, unlikely, that, this, patient, has, mutations, in, other, genes, that, cause, 'PTH-deficient', 'hypoparathyroidism,', in, addition, to, the, 'GATA3', mutation, described, here])]). relacion([sujeto(['During', 'T', helper, '(', 'Th)', cell, 'differentiation,', 'GATA3']), verbo([induces]), complemento([the, 'Th2', and, suppresses, the, 'Th1', pathway])]). relacion([sujeto(['Stimulation', of, the, 'T', cell, receptor, '(', 'TCR)', of, naive, 'Th', cells, in, the, presence, of, interleukin, 4, '(', 'IL-4)']), verbo([induces]), complemento([robust, expression, of, 'GATA3;', 'however,', it, is, unclear, where, these, signals, integrate])]). relacion([sujeto(['However,', the, establishment, of, the, activity, of, the, distal, promoter, is, totally, dependent, on, 'STAT6,', whereas, it, is, likely, that, the, proximal, promoter]), verbo([has]), complemento([additional, activation, mechanisms, that, are, 'STAT6', independent])]). relacion([sujeto(['Our', findings]), verbo([suggest]), complemento([that, different, combinations, of, transcription, factors, downstream, of, the, 'IL-4', receptor, '(', 'IL-4R)', and, 'TCR', finely, modulate, 'Gata3', gene, expression, from, its, two, promoters, for, optimal, 'Th2', differentiation])]). relacion([sujeto(['The', data]), verbo([reveal]), complemento([that, 'Eomesodermin', compensates, 'T-bet', deficiency, for, 'IFN-gamma', and, 'Th1', development])]). relacion([sujeto(['In', contrast, to, 'IL-6', plus, 'TGFbeta-driven', 'Th17,', 'IL-6-driven', 'Th17', cells, do, not]), verbo([express]), complemento(['IL-10', and, they, induce, a, more, intense, colitis])]). relacion([sujeto(['Naive', 'CD4', 'T', cells, deficient, in, 'Stat6', and, 'T-bet', also]), verbo([induce]), complemento([a, 'Th17-dominant', colitis, development, in, vivo])]). relacion([sujeto(['Our', data]), verbo([provide]), complemento([new, insights, into, the, choice, between, 'Th1', and, 'Th17', development, and, their, roles, in, autoimmunity])]). relacion([sujeto(['Viperin', '(', virus, inhibitory, 'protein,', endoplasmic, reticulum, '[', 'ER]-associated,', 'interferon-inducible)']), verbo([has]), complemento([been, identified, as, a, highly, inducible, 'ER', protein, that, has, antiviral, activity])]). relacion([sujeto(['In', 'parallel,', 'viperin-deficient', 'T', cells, showed]), verbo([decreases]), complemento([in, 'NF-kappaB1/p50', and, 'AP-1/JunB', 'DNA', binding, activities, after, 'TCR', engagement])]). relacion([sujeto(['Thus,', viperin, facilitates, 'TCR-mediated', 'GATA-3', activation, and, optimal, 'Th2', cytokine, production, by]), verbo([modulating]), complemento(['NF-kappaB', and, 'AP-1', activities])]). relacion([sujeto(['A', recurring, theme, in, 'post-thymic', 'CD4', 'T', cell, differentiation, is, the, 'cross-regulation', of, lineage, choice, by, cytokines, and, transcription, factors, that, are]), verbo([expressed]), complemento([in, alternative, lineages])]). relacion([sujeto(['For', 'example,', 'TGFbeta']), verbo([induces]), complemento([the, de, novo, expression, of, the, 'Treg', cell, signature, transcription, factor, 'Foxp3,', but, iTreg, differentiation, is, blocked, by, high, concentrations, of, the, 'Th2', cytokine, 'IL4'])]). relacion([sujeto(['Here', we, use, a, 'co-culture', system, to, demonstrate, that, 'IL4']), verbo([provided]), complemento([by, 'Th2', cells, in, vitro, is, sufficient, to, block, 'Foxp3', induction, in, naive, 'CD4', 'T', cells])]). relacion([sujeto(['In', 'addition,', we]), verbo([find]), complemento([that, 'Foxp3', induction, is, efficiently, blocked, not, only, by, the, 'Th2', transcription, factor, 'Gata3,', but, also, by, 'PU'])]). relacion([sujeto([1, ',', which, is, transiently]), verbo([induced]), complemento([during, 'Th2', differentiation])]). relacion([sujeto(['These', data]), verbo([suggest]), complemento([that, iTreg, differentiation, may, be, affected, by, the, polarity, of, immune, responses])]). relacion([sujeto(['These', cells, progressively]), verbo([decreased]), complemento([in, cultures, from, young, subjects, whereas, they, remained, at, very, low, levels, in, old, donors])]). relacion([sujeto(['The', supplementation, with, zinc, greatly]), verbo([increased]), complemento([the, number, of, cells, in, culture, and, the, percentage, and, the, cytotoxic, activity, of, 'NK', cells, both, in, young, and, old, ages])]). relacion([sujeto(['In', zinc, supplemented, 'cultures,', a, 3.6, -, fold, and, a, 4.1, -, fold]), verbo([increased]), complemento([expression, of, 'GATA-3', transcription, factor, was, observed, in, young, and, old, 'donors,', respectively])]). relacion([sujeto(['Major', transcription, factors, controlling, 'T(H)1', and, 'T(H)2', 'development,', such, as, 'T-box', transcription, factor, and, 'GATA3,', might, be, centrally]), verbo([involved]), complemento([in, asthma, and, atopic, diseases])]). relacion([sujeto([20, -, like, homeobox, 1, '(', 'HLX1),']), verbo([interacting]), complemento([closely, with, 'T-box', transcription, 'factor,', has, been, identified, as, an, important, regulator, of, 'T(H)1', differentiation, and, suppressor, of, 'T(H)2', commitment])]). relacion([sujeto(['Nineteen', polymorphisms, were, identified, in, the, 'HLX1', 'gene,', and, 2, tagging, single, nucleotide, polymorphisms, representing, 7, polymorphisms, were]), verbo([associated]), complemento([with, childhood, asthma, in, our, study, population])]). relacion([sujeto(['Two', promoter, 'polymorphisms,', 'C-1407T', and, 'C-742G,', contained, in, 1, tagging, block, were]), verbo([associated]), complemento([with, asthma, '(', odds, 'ratio,', 1.44, ;, 95, '%', 'CI,', 1.11, -, 1.86, ;, 'P', =])]). relacion([sujeto([61, ')', ',', significantly]), verbo([decrease]), complemento([promoter, 'transactivation,', and, disrupt, specificity, 'protein-transcription', factor, binding, in, in, vitro, experiments])]). relacion([sujeto(['Our', data]), verbo([suggest]), complemento([that, polymorphisms, in, the, 'HLX1', gene, increase, the, risk, for, childhood, asthma])]). relacion([sujeto(['On', the, cellular, 'level,', altered]), verbo([binding]), complemento([of, specificity, 'protein-transcription', factors, to, the, 'HLX1', promoter, and, subsequent, changes, in, 'HLX1', gene, expression, might, contribute, to, these, effects])]). relacion([sujeto(['GATA3', gene, encodes, a, transcription, factor]), verbo([expressed]), complemento([during, 'thymus,', 'liver,', 'kidney,', adrenal, 'gland,', central, and, peripheral, nervous, 'systems,', placenta, and, 'T', lymphocytes, embryonic, development])]). relacion([sujeto(['Mutations', of, 'GATA3']), verbo([cause]), complemento(['Hypoparathyroidism,', sensorineural, 'Deafness', and, 'Renal', dysplasia, syndrome, '(', 'HDR)'])]). relacion([sujeto(['We']), verbo([report]), complemento([the, case, of, a, girl, with, a, terminal, deletion, of, the, short, arm, of, chromosome, 10, '(', 10, p12])]). relacion([sujeto(['The', girl, developed, chronic, renal, failure, during, the, first, year, of, 'life,']), verbo([associated]), complemento([with, sensorineural, hearing, 'loss,', facial, dysmorphic, features, and, psychomotor, development])]). relacion([sujeto(['Our', patient, is, the, first, case, with, a, large, deletion, of, the, short, arm, of, chromosome, 10, -, that, certainly]), verbo([involves]), complemento(['DGCR2', -, with, the, 'HDR', phenotype, but, without, the, clinical, features, of, 'DGS2'])]). relacion([sujeto(['This', peculiarity]), verbo([suggests]), complemento([the, hypothesis, that, the, mechanisms, underlying, this, syndrome, may, be, more, complex])]). relacion([sujeto(['The', 'GATA3', transcription, factor, is]), verbo([expressed]), complemento([in, many, tissues, such, as, the, immune, 'system,', 'kidney,', 'brain,', 'endometrium,', and, mammary, epithelial, cells])]). relacion([sujeto(['One', of, the, most, interesting, questions, raised, is, whether, 'GATA3', will, be]), verbo([involved]), complemento([in, the, same, pathways, in, every, tissue, or, will, be, involved, in, distinct, regulatory, networks, within, different, tissue, 'types?', 'While', previous, studies, may, imply, the, 'latter,', with, some, known, targets, of, 'GATA3', perhaps, being, specific, to, 'cell-type', or, 'tissue-type,', the, question, has, not, been, systematically, addressed, until, now])]). relacion([sujeto(['With', the, advent, of, techniques, such, as, 'co-expression', 'meta-analysis', a, better, understanding, of, the, pathway, partners, of, 'GATA3', can, be, obtained, and, specifically, the, partners, within, different, tissue, types, can, be, 'found,', yielding]), verbo([leads]), complemento([for, future, studies])]). relacion([sujeto(['Here,', a, recent, technique, of, 'meta-analysis', from, the, 'Oncomine', database]), verbo([has]), complemento([been, employed, to, probe, this, very, question])]). relacion([sujeto(['Data', obtained, implies, that, 'GATA3', is]), verbo([involved]), complemento([in, distinct, pathways, in, different, tissue, types])]). relacion([sujeto(['Compared', with, model, 'group,', the]), verbo([decreased]), complemento([content, of, 'IL-4(49'])]). relacion([sujeto([30, +, /, -, 7.95, ')', ng, x, 'L(-1)', and]), verbo([increased]), complemento([level, of, 'IFN-gamma', '(', 49.08, x, 5.46, ')', ng, x, 'L(-1)'])]). relacion([sujeto([were]), verbo([found]), complemento([in, 'BALF,', and, the, level, of, total, 'IgE', '(', 9.47, +, /, -, 1.52, ')', microg, x, 'L(-1)', in, serum, also, decreased, in, 'TFG', treated, group])]). relacion([sujeto(['Expression', of, 'GATA-3', was, markly]), verbo([increased]), complemento([in, model, group, with, decreased, expression, in, 'TFG', treated, group])]). relacion([sujeto(['Nebulized', 'TFG', showed, a, therapeutic, effect, for, asthmatic, 'mice,', the, mechanism, may, be, explained, by, blockingnnnn, 'GATA-3', expression, and]), verbo([regulating]), complemento([the, disorder, 'Th1/Th2', imbalance])]). relacion([sujeto(['Progressive']), verbo([loss]), complemento([of, 'T', cell, functionality, is, a, hallmark, of, chronic, infection, with, human, immunodeficiency, virus, 1, '(', 'HIV-1)'])]). relacion([sujeto(['We']), verbo([have]), complemento([identified, a, novel, population, of, dysfunctional, 'T', cells, marked, by, surface, expression, of, the, glycoprotein, 'Tim-3'])]). relacion([sujeto(['The', frequency, of, this, population, was]), verbo([increased]), complemento([in, 'HIV-1-infected', individuals, to, a, mean, of, 49.4, +, /, -, 'SD', 12.9, '%', of, 'CD8(+)', 'T', cells, expressing, 'Tim-3', in, 'HIV-1-infected', chronic, progressors, versus, 28.5, +, /, -, 6.8, '%', in, 'HIV-1-uninfected', individuals])]). relacion([sujeto(['Blocking', the, 'Tim-3', signaling, pathway, restored, proliferation, and]), verbo([enhanced]), complemento([cytokine, production, in, 'HIV-1-specific', 'T', cells])]). relacion([sujeto(['Thus,', 'Tim-3', represents, a, novel]), verbo([target]), complemento([for, the, therapeutic, reversal, of, 'HIV-1-associated', 'T', cell, dysfunction])]). relacion([sujeto(['Transforming', growth, 'factor-beta', '(', 'TGF-beta)']), verbo([induces]), complemento(['Foxp3', and, suppressive, 'T(reg)', cells, from, naive, 'T', 'cells,', whereas, interleukin, 6, '(', 'IL-6)', inhibits, the, generation, of, inducible, 'T(reg)', cells])]). relacion([sujeto(['Here', we, show, that, 'IL-4', blocked, the, generation, of, 'TGF-beta-induced', 'Foxp3(+)', 'T(reg)', cells, and, instead]), verbo([induced]), complemento([a, population, of, 'T', helper, cells, that, produced, 'IL-9', and, 'IL-10'])]). relacion([sujeto(['Adoptive', transfer, of, 'IL-9(+)IL-10(+)', 'T', cells, into, 'recombination-activating', gene, 1, -, deficient, mice]), verbo([induced]), complemento([colitis, and, peripheral, 'neuritis,', the, severity, of, which, was, aggravated, if, the, 'IL-9(+)IL-10(+)', 'T', cells, were, transferred, with, 'CD45RB(hi)', 'CD4(+)', effector, 'T', cells])]). relacion([sujeto(['Thus', 'IL-9(+)IL-10(+)', 'T', cells, lack, suppressive, function, and, constitute, a, distinct, population, of, 'helper-effector', 'T', cells, that]), verbo([promote]), complemento([tissue, inflammation])]). relacion([sujeto(['Genes', in, the, categories, '(', 'a)', homeobox]), verbo([binding]), complemento([and, transcription, 'factors,', '(', 'b)', growth, factors, and, 'receptors,', '(', 'c)', brain, and, neural, specific, factors, and, '(', 'd)', serotonin, specific, factors, are, reported])]). relacion([sujeto(['In', the, serotonin, developmental, 'cascade,', 'FGFR2', was, robustly]), verbo([expressed]), complemento([at, each, stage])]). relacion([sujeto(['GATA3', was, robustly]), verbo([expressed]), complemento([in, 'EBs'])]). relacion([sujeto(['A', majority, of, the, examined, genes, were]), verbo([expressed]), complemento([in, adult, serotonin, neurons])]). relacion([sujeto(['This', analysis]), verbo([suggests]), complemento([that, the, 366.4, cell, line, possesses, cues, for, serotonin, differentiation, at, early, stages, of, 'differentiation,', but, that, 'ESC-derived', serotonin, neurons, are, still, immature])]). relacion([sujeto(['At', embryonic, day, 8.5, ',', the, 'LIM-homeodomain', factor, 'Lmx1a', is]), verbo([expressed]), complemento([throughout, the, otic, placode, but, becomes, developmentally, restricted, to, 'non-sensory', epithelia, of, the, ear, '(', endolymphatic, 'duct,', ductus, 'reuniens,', cochlea, lateral, 'wall)'])]). relacion([sujeto(['Hair', cell, markers, such, as, 'Atoh1', and, 'Myo7', 'reveal,', for, the, first, 'time,', that, newborn, 'Lmx1a', mutants]), verbo([have]), complemento([only, three, sensory, 'epithelia:', two, enlarged, canal, cristae, and, one, fused, epithelium, comprising, an, amalgamation, of, the, 'cochlea,', 'saccule,', and, utricle, '(', a, &, 'quot;cochlear-gravistatic"', 'endorgan)'])]). relacion([sujeto(['These', changes, in, 'Sox2', and, 'Prox1', expression]), verbo([suggest]), complemento([that, 'Lmx1a', expression, restricts, and, sharpens, 'Sox2', 'expression,', thereby, defining, 'non-sensory', and, sensory, epithelium])]). relacion([sujeto(['The', adult, 'Lmx1a', mutant, organ, of, 'Corti', shows, a]), verbo([loss]), complemento([of, cochlear, hair, 'cells,', suggesting, that, the, 'long-term', maintenance, of, hair, cells, is, also, disrupted, in, these, mutants])]). relacion([sujeto(['Allergic', asthma, is]), verbo([caused]), complemento([by, aberrant, helper, 'T', '(', 'T(H))', type, 2, immune, responses, in, susceptible, 'individuals,', characterized, by, airway, 'hyperresponsiveness,', chronic, airway, 'inflammation,', and, mucus, hypersecretion])]). relacion([sujeto(['The', transcription, factor, 'T-bet', is, a, master, regulator, of, 'T(H)1', lineage, commitment, and, strongly]), verbo([promotes]), complemento([interferon, gamma, expression, during, 'T(H)1', cell, differentiation])]). relacion([sujeto(['Intranasal', administration, of, 'AAV-T-bet', efficiently, balanced, the, 'T(H)1/T(H)2', transcription, factor, and, cytokine, profile, and, significantly]), verbo([decreased]), complemento([the, number, of, eosinophils, in, 'BAL', fluid])]). relacion([sujeto(['Our', data, show, that, intranasal, delivery, of, 'T-bet', can]), verbo([promote]), complemento([a, 'T(H)1', immune, 'response,', restore, a, balanced, 'Th', immune, 'response,', and, inhibit, airway, inflammation, during, the, challenge, phase, in, a, mouse, model, of, allergic, airway, inflammation])]). relacion([sujeto([5, ')', 'Gata3-LacZ', activity, recapitulated, endogenous, 'Gata3', and, was, abundantly]), verbo([expressed]), complemento([in, the, endocardial, ridges, and, endothelium, of, distal, outflow, tract])]). relacion([sujeto(['Collaborative', mutations]), verbo([causing]), complemento([a, reduction, in, 'Ikaros', activity, and, an, increase, in, 'Notch', activation, promote, 'T', cell, leukemogenesis])]). relacion([sujeto(['Although', the, molecular, mechanisms, of, this, cooperation]), verbo([have]), complemento([been, 'studied,', its, consequences, in, thymocyte, development, remain, unexplored])]). relacion([sujeto(['In', this, 'study,', we, show, that, 'Ikaros']), verbo([regulates]), complemento([expression, of, a, subset, of, 'Notch', target, 'genes,', including, 'Hes1,', 'Deltex1,', 'pTa,', 'Gata3,', and, 'Runx1,', in, both, 'Ikaros', null, 'T', cell, leukemia, lines, and, 'Ikaros', null, primary, thymocytes])]). relacion([sujeto(['In', 'Ikaros', null, leukemia, 'cells,', 'Notch', deregulation, occurs, at, both, the, level, of, 'Notch', receptor, cleavage, and, expression, of, 'Notch']), verbo([target]), complemento(['genes,', because, 're-expression', of, 'Ikaros', in, these, cells, 'down-regulates', 'Notch', target, gene, expression, without, affecting, levels, of, intracellular, cleaved, 'Notch'])]). relacion([sujeto(['In', 'addition,', abnormal, expression, of, 'Notch']), verbo([target]), complemento([genes, is, observed, in, 'Ikaros', null, 'double-positive', 'thymocytes,', in, the, absence, of, detectable, intracellular, cleaved, 'Notch'])]). relacion([sujeto(['Finally,', we, show, that, this, role, of, 'Ikaros', is, specific, to, 'double-positive', and, 'single-positive', thymocytes, because, derepression, of, 'Notch']), verbo([target]), complemento([gene, expression, is, not, observed, in, 'Ikaros', null, 'double-negative', thymocytes, or, 'lineage-depleted', bone, marrow])]). relacion([sujeto(['Thus,', in, this, 'study,', we]), verbo([provide]), complemento([evidence, that, 'Ikaros', and, 'Notch', play, opposing, roles, in, regulation, of, a, subset, of, 'Notch', target, genes, and, that, this, role, is, restricted, to, developing, thymocytes, where, 'Ikaros', is, required, to, appropriately, regulate, the, 'Notch', program, as, they, progress, through, 'T', cell, development])]). relacion([sujeto(['In', the, cluster, 'group,', serum, levels, of, specific, 'IgG(Mite)', '(', p, &, 'lt;', 0.001, ')', and, specific, 'IgG4(Mite)', '(', p, &, 'lt;', 0.001, ')', significantly]), verbo([increased]), complemento([after, 8, 'weeks,', while, it, took, 12, weeks, in, the, classic, 'SIT', group])]). relacion([sujeto(['These', data, were, confirmed, by, blocking, 'CD63', expression, as, well, as]), verbo([release]), complemento([of, cysteinyl, leukotrienes, after, in, vitro, basophil, stimulation])]). relacion([sujeto(['No', differences, in, transcription, factor, expression, were]), verbo([found]), complemento([in, the, two, groups])]). relacion([sujeto(['The', 6, -, sulfated, lactosamine, glycans, in, particular]), verbo([have]), complemento([been, widely, noted, for, their, importance, because, they, are, involved, in, cell, recognition, events, mediated, by, 'cell-adhesion', molecules, such, as, selectins, and, sialic, 'acid-recognizing', molecules, such, as, siglecs, and, also, in, the, activation, of, 'CD44', in, binding, to, extracellular, matrix, hyaluronate])]). relacion([sujeto(['A', 'pro-inflammatory', 'cytokine,', tumor, necrosis, 'factor-alpha,']), verbo([induces]), complemento([expression, of, 6, -, sulfated, glycans, on, human, leukocytes])]). relacion([sujeto(['Here', we]), verbo([report]), complemento([that, the, transcription, of, the, 'GlcNAc6ST-1', 'gene,', the, gene, encoding, a, sulfotransferase, for, 6, -, sulfated, glycan, 'synthesis,', is, induced, in, human, 'T-lymphoid', cells, through, tandem, 'NF-kappaB', and, 'GATA', motifs, in, its, 5, '\'', -, regulatory, region])]). relacion([sujeto(['Results', of, our, reporter, 'assays,', 'immunoprecipitation,', and, chromatin, immunoprecipitation, analyses, indicated, that, 'GATA-3', 'and/or', 'GATA-2,', but, not, 'GATA-1,']), verbo([associates]), complemento([with, 'NF-kappaB', in, a, transcription, factor, complex, on, the, 5, '\'', -, regulatory, region, of, the, gene, and, acts, synergistically, with, 'NF-kappaB', in, triggering, 'GlcNAc6ST-1', transcription])]). relacion([sujeto(['Recently,', a, 'skin-homing', subset, of, helper, memory, 'T', cells, exhibiting, the, 'Th2', marker, 'CCR4', was, shown, to, specifically]), verbo([express]), complemento([6, -, sulfated, glycans])]). relacion([sujeto(['The', transactivation, mechanism, described, here]), verbo([suggested]), complemento([that, 'GlcNAc6ST-1', transcription, is, coordinated, with, the, 'NF-kappaB/GATA-3', 'axis,', which, is, known, to, figure, heavily, in, 'Th2', cell, differentiation])]). relacion([sujeto(['In', line, with, 'this,', in, vitro, differentiation, of, human, 'T', cells, to, 'Th2', cells, was]), verbo([found]), complemento([to, significantly, induce, 'GlcNAc6ST-1', transcription, and, 6, -, sulfated, glycan, expression])]). relacion([sujeto(['The', 'SNP', at, rs1269486, of, 'GATA3', is]), verbo([associated]), complemento([with, allergic, rhinitis, in, 'Chinese'])]). relacion([sujeto(['We']), verbo([report]), complemento([here, that, the, new, cytokine, 'IL-33,', in, the, presence, of, 'Ag,', polarizes, murine, and, human, naive, 'CD4(+)', 'T', cells, into, a, population, of, 'T', cells, which, produce, mainly, 'IL-5', but, not, 'IL-4'])]). relacion([sujeto(['This', polarization]), verbo([requires]), complemento(['IL-1R-related', molecule, and, 'MyD88', but, not, 'IL-4', or, 'STAT6'])]). relacion([sujeto(['Conversely,', 'IL-33', administration]), verbo([induced]), complemento([the, 'IL-5-producing', 'T', cells, and, exacerbated, 'allergen-induced', airway, inflammation, in, 'wild-type', as, well, as, 'IL-4(-/-)', mice])]). relacion([sujeto(['Finally,', adoptive, transfer, of, 'IL-33-polarized', 'IL-5(+)IL-4(-)T', cells]), verbo([triggered]), complemento([airway, inflammation, in, naive, 'IL-4(-/-)', mice])]). relacion([sujeto(['Thus,', we, demonstrate, here, 'that,', in, the, presence, of, 'Ag,', 'IL-33']), verbo([induces]), complemento(['IL-5-producing', 'T', cells, and, promotes, airway, inflammation, independent, of, 'IL-4'])]). relacion([sujeto(['The', 'ER', can, be]), verbo([activated]), complemento([by, oestrogen, or, activated, due, to, &, 'quot;crosstalk"', with, growth, factor, receptor, pathways])]). relacion([sujeto(['Immunohistochemistry', '(', 'IHC),', in, spite, of, the, 'shortcomings,', remains, the, method, of, choice, as, it]), verbo([provides]), complemento([for, in, situ, assessment, of, 'ER', expression, within, the, tumour, cells])]). relacion([sujeto(['Several', areas, of, 'ER', biology, are, still, poorly, 'understood;', these, 'include:', its, function, in, the, 'cytoplasm/plasma', 'membrane,', its, role, in, the, differentiation, to, proliferation, 'switch,', and, pathways]), verbo([associated]), complemento([with, resistance, to, hormonal, therapy])]). relacion([sujeto(['Legionella', pneumophila, infection, of, mice]), verbo([induces]), complemento([proinflammatory, cytokines, and, 'Th1', immunity, as, well, as, rapid, increases, in, serum, levels, of, 'IL-12', and, 'IFNgamma', and, splenic, 'IL-12Rbeta2', expression])]). relacion([sujeto(['Delta-9-tetrahydrocannabinol', '(', 'THC)', treatment, prior, to, infection]), verbo([causes]), complemento([a, shift, from, 'Th1', to, 'Th2', immunity, and, here, we, demonstrate, that, 'CB(1)', and, 'CB(2)', cannabinoid, receptors, mediate, different, aspects, of, the, shift])]). relacion([sujeto(['Using', cannabinoid, receptor, antagonists, and, cannabinoid, receptor, gene, deficient, mice, '(', 'CB(1)', '(', -, /, -, ')', and, 'CB(2)', '(', -, /, -, ')', ')', ',', we, showed, that, both, 'CB(1)', and, 'CB(2)', receptors, were]), verbo([involved]), complemento([in, the, 'THC-induced', attenuation, of, serum, 'IL-12', and, 'IFNgamma'])]). relacion([sujeto(['IFNgamma', production, is, dependent, upon, signaling, through, 'IL-12Rbeta2', '(', 'beta2)', and, 'THC', treatment]), verbo([suppressed]), complemento([splenic, beta2, 'message;', 'moreover,', this, effect, was, 'CB(1)', but, not, 'CB(2)-dependent', from, studies, with, receptor, antagonists, and, 'CB1(-/-)', and, 'CB2(-/-)', mice])]). relacion([sujeto(['Furthermore,', observed]), verbo([increases]), complemento([in, 'IL-4', induced, by, 'THC,', were, not, involved, in, the, drug, effect, on, beta2, from, studies, with, 'IL-4', deficient, mice])]). relacion([sujeto(['The', 'GATA-3', transcription, factor, is, necessary, for, 'IL-4', production, and, is, selectively]), verbo([expressed]), complemento([in, 'Th2', cells])]). relacion([sujeto(['Furthermore,', 'GATA-3', regulatory, factors, were]), verbo([modulated]), complemento([in, that, 'Notch', ligand, 'Delta4', mRNA, was, decreased, and, 'Jagged1', increased, by, 'THC', also, in, a, 'CB2-dependent', manner, and, splenic, 'NFkappaB', p65, was, increased])]). relacion([sujeto(['Together,', these, results, indicate, that, 'CB(1)', and, 'CB(2)']), verbo([mediate]), complemento([the, 'THC-induced', shift, in, 'T', helper, activity, in, 'L'])]). relacion([sujeto(['pneumophila-infected', 'mice,', with, 'CB(1)']), verbo([involved]), complemento([in, suppressing, 'IL-12Rbeta2', and, 'CB(2)', involved, in, enhancing, 'GATA-3'])]). relacion([sujeto(['The', 'zinc-finger', transcription, factor, 'GATA3', serves, as, a, master, regulator, of, 'T-helper-2', '(', 'Th2)', differentiation, by]), verbo([inducing]), complemento([expression, of, the, 'Th2', cytokines, 'IL-4,', 'IL-5', and, 'IL-13', and, by, suppressing, 'Th1', development])]). relacion([sujeto(['We']), verbo([activated]), complemento([naïve, primary, 'T', cells, in, vitro, in, the, presence, of, transforming, growth, 'factor-beta', and, 'IL-6,', and, found, that, enforced, 'GATA3', expression, induced, 'co-expression', of, 'Th2', cytokines, in, 'IL-17-producing', 'T', cells])]). relacion([sujeto(['GATA3', additionally, constrained, 'Th17', differentiation, in, vitro, through, 'IL-4-independent', 'mechanisms,']), verbo([involving]), complemento([downregulating, transcription, of, 'STAT3,', 'STAT4,', 'NFATc2', and, the, nuclear, factor, 'RORgammat,', which, is, crucial, for, 'Th17', differentiation])]). relacion([sujeto(['We', therefore, conclude, that, although, 'GATA3', allows, 'Th17', 'differentiation,', it]), verbo([acts]), complemento([as, an, inhibitor, of, 'Th17-mediated', 'pathology,', through, 'IL-4-dependent', and, 'IL-4-independent', pathways])]). relacion([sujeto(['However,', a, pronounced, amelioration, of, macroscopic, score, and, cartilage, destruction, was]), verbo([found]), complemento([in, mouse, treated, with, shikonin, on, established, 'CIA', for, 10, days])]). relacion([sujeto(['Moreover,', 'The', mRNA, levels, of, 'Th1', cytokines, '[', tumor, necrosis, 'factor-alpha', and, interleukin, '(', 'IL)-12]', was, significantly]), verbo([inhibited]), complemento([both, in, the, synovial, tissue, and, in, the, articular, cartilage, in, treated, groups, compared, with, those, in, control, 'groups,', whereas, the, mRNA, and, protein, levels, of, 'Th2', cytokines, '(', 'IL-10', and, 'IL-4)', remained, elevated, throughout, the, treatment, period])]). relacion([sujeto(['T-box']), verbo([expressed]), complemento([in, 'T', cells, '(', 'T-bet)', mRNA, levels, were, decreased, in, shikonin, compared, with, control, 'group,', and, 'GATA-3', mRNA, levels, were, higher, than, that, in, control, group])]). relacion([sujeto(['Shikonin', treatment, on, established, 'CIA', can]), verbo([inhibit]), complemento(['Th1', cytokines, expression, and, induce, 'Th2', cytokines, expression, in, mice, with, established, 'CIA'])]). relacion([sujeto(['The']), verbo([inhibited]), complemento([effect, of, shikonin, on, 'Th1', cytokines, expression, may, be, mediated, not, only, by, inhibiting, 'Th1', responses, through, 'T-bet', 'mechanism,', but, also, by, inducing, 'anti-inflammatory', mediators, such, as, 'IL-10', and, 'IL-4', through, a, 'GATA-3', dependent, mechanism])]). relacion([sujeto(['The', transcription, factors, 'GATA-3', and, 'ThPOK', are]), verbo([required]), complemento([for, intrathymic, differentiation, of, 'CD4(+)', 'T', 'cells,', but, their, precise, functions, in, this, process, remain, unclear])]). relacion([sujeto(['GATA-3']), verbo([promoted]), complemento(['ThPOK', expression, and, bound, to, a, region, of, the, locus, encoding, 'ThPOK', established, as, being, critical, for, 'ThPOK', expression])]). relacion([sujeto(['Finally,', 'ThPOK']), verbo([promoted]), complemento([differentiation, into, the, 'CD4(+)', lineage, in, a, way, dependent, on, 'GATA-3', but, inhibited, differentiation, into, the, 'CD8(+)', lineage, independently, of, 'GATA-3'])]). relacion([sujeto(['We', propose, that, 'GATA-3']), verbo([acts]), complemento([as, a, specification, factor, for, the, 'CD4(+)', lineage, '\'', 'upstream\'', of, the, 'ThPOK-controlled', 'CD4(+)', commitment, checkpoint])]). relacion([sujeto(['The', proliferation, of, 'SKRC06', was]), verbo([inhibited]), complemento([with, cRA, 'treatment;', the, proliferation, of, 'SKRC39', was, not])]). relacion([sujeto(['Combination', treatment, of, cells, with, both, 'SAHA', and, cRA]), verbo([induced]), complemento([several, transcripts, with, known, 'anti-cancer/immunomodulatory', 'effects,', including, 'dhrs9,', 'gata3,', 'il1beta,', 'phlda1,', txk, and, vhl])]). relacion([sujeto(['Immunostaining', confirmed, the]), verbo([decreased]), complemento([expression, of, gata3, in, human, 'RCC', specimens, compared, to, normal, kidney])]). relacion([sujeto(['Together,', our, results, show, that, treatment, of, 'RCC', with, cRA, 'and/or', 'SAHA']), verbo([increases]), complemento([the, expression, of, several, genes, and, gene, families, that, result, in, reduced, cell, proliferation])]). relacion([sujeto(['The', underlying, regulatory, basis, of, this, plasticity, is, that, early, 'T-cell', differentiation, depends, on, transcription, factors, which, can, also]), verbo([promote]), complemento([alternative, developmental, programs])]). relacion([sujeto(['Here', the, pathways]), verbo([leading]), complemento([to, several, lineage, alternatives, for, early, 'pro-T-cells', are, 'reviewed,', with, close, focus, on, the, mechanisms, of, action, of, three, vital, 'factors,', 'GATA-3,', 'PU'])]). relacion([sujeto(['The', 'T(h)1/T(h)2', paradigm]), verbo([has]), complemento([been, used, for, decades, to, characterize, phenotypically, different, immune, responses])]). relacion([sujeto(['The', model, is, able, to, describe, any, number, of, master, regulators, and, is, grounded, on, transcription, factors]), verbo([binding]), complemento([promoter, sites, and, binding, each, other])]). relacion([sujeto(['Furthermore,', the, model, accounts, for, the, kinetics, of, 'FoxP3', and, 'GATA3', mRNA, expression, measured, after]), verbo([stimulating]), complemento([naive, helper, '(', 'CD4+CD45RA+)', 'T', cells, under, various, circumstances])]). relacion([sujeto(['Due', to, its, 'n-dimensional', 'character,', this, model, may, easily, be, applied, to, other, developmental, processes, that]), verbo([involve]), complemento([master, regulators])]). relacion([sujeto(['Previously', we]), verbo([have]), complemento([demonstrated, that, bradykinin, 'B1', receptor, deficient, mice, '(', 'B1KO)', were, protected, against, renal, ischemia, and, reperfusion, injury, '(', 'IRI)'])]). relacion([sujeto(['Here,', we, aimed, to, analyze, the, effect, of, 'B1', antagonism, on, renal, 'IRI', and, to, study, whether, 'B1R', knockout, or, antagonism, could]), verbo([modulate]), complemento([the, renal, expression, of, pro, and, 'anti-inflammatory', molecules])]). relacion([sujeto(['Herein,', 'B1R', antagonism, '(', 'R-954)', was, able, to]), verbo([decrease]), complemento([serum, creatinine, 'levels,', whereas, 'B2R', antagonism, had, no, effect])]). relacion([sujeto(['The', protection, seen, under, 'B1R', deletion, or, antagonism, was]), verbo([associated]), complemento([with, an, increased, expression, of, 'GATA-3,', 'IL-4', and, 'IL-10', and, a, decreased, 'T-bet', and, 'IL-1beta', transcription])]). relacion([sujeto(['CD154', expression, is, tightly]), verbo([regulated]), complemento([and, largely, restricted, to, activated, 'CD4', 'T', cells])]). relacion([sujeto(['Approximately', 350, bp, of, 'DNA', sequence, flanking, the, upstream, 'HSS', site, was, highly]), verbo([conserved]), complemento([between, mouse, and, 'man,', and, was, rich, in, binding, sites, for, 'GATA', and, 'NFAT', proteins])]). relacion([sujeto(['Gel', shift, and, chromatin, immunoprecipitation, assays, demonstrated, both, 'NFAT1', and, the, 'Th2', 'factor,', 'GATA-3,']), verbo([bound]), complemento([this, enhancer, element, in, vitro, and, in, 'vivo,', respectively])]). relacion([sujeto(['A', 'PstI/XbaI', 345, bp, fragment, of, this, region]), verbo([acted]), complemento([as, a, transcriptional, enhancer, of, the, 'CD154', promoter, in, primary, human, 'CD4', 'T', cells])]). relacion([sujeto(['Overexpression', of, repressor, of, 'GATA', and, a, dominant, negative, 'GATA-3', protein, independently]), verbo([inhibited]), complemento(['transcription,', whereas, overexpression, of, 'wild-type', 'GATA-3', enhanced, transcriptional, 'activity,', by, this, element, in, primary, 'CD4', 'T', cells])]). relacion([sujeto(['Moreover,', more, 'interleukin-4-producing', 'CD4', 'T', cells]), verbo([expressed]), complemento(['CD154', following, activation, than, 'interferon-gamma-producing', 'CD4', 'T', cells])]). relacion([sujeto(['Thus,', we, identified, a, novel, 'T-cell-specific,', 'GATA-3', 'responsive,', 'CD154', transcriptional, 'enhancer,', which, may, contribute, to]), verbo([increased]), complemento([propensity, of, 'Th2', cells, to, express, 'CD154'])]). relacion([sujeto(['The', 'IL-18Ralpha-chain', is]), verbo([expressed]), complemento([on, 'Th1', but, not, 'Th2', cells])]). relacion([sujeto(['We']), verbo([have]), complemento([recently, shown, that, 'Stat4', is, an, important, component, of, programming, the, 'Il18r1', locus, '(', encoding, 'IL-18Ralpha)', for, maximal, expression, in, 'Th1', cells])]). relacion([sujeto(['Stat6', is]), verbo([required]), complemento([for, the, repression, of, 'Il18r1', expression, and, in, 'Stat6-deficient', 'Th2', 'cultures,', mRNA, 'levels,', histone, 'acetylation,', and, 'H3K4', methylation, levels, are, intermediate, between, levels, observed, in, 'Th1', and, 'Th2', cells])]). relacion([sujeto(['Despite', the, repressive, effects, of, 'IL-4', during, 'Th2', 'differentiation,', we, observed, only, modest]), verbo([binding]), complemento([of, 'Stat6', to, the, 'Il18r1', locus])]). relacion([sujeto(['In', 'contrast,', we, observed, robust, 'GATA-3']), verbo([binding]), complemento([to, a, central, region, of, the, locus, where, 'DNase', hypersensitivity, sites, overlapped, with, conserved, 'non-coding', sequences, in, 'Il18r1', introns])]). relacion([sujeto(['These', data]), verbo([provide]), complemento([further, mechanistic, insight, into, transcription, 'factor-dependent', establishment, of, 'Th', 'subset-specific', patterns, of, gene, expression])]). relacion([sujeto(['The', differentiation, of, naive, 'CD4', 'T', cells, into, 'Th2', cells]), verbo([requires]), complemento([the, 'T', cell, 'receptor-mediated', activation, of, the, 'ERK', 'MAPK', cascade])]). relacion([sujeto(['Little', is, 'known,', 'however,', in, regard, to, how, the, 'ERK', 'MAPK', cascade]), verbo([regulates]), complemento(['Th2', cell, differentiation])]). relacion([sujeto(['We', herein, identified, 'Gfi1', '(', growth, factor, 'independent-1)', as, a, downstream]), verbo([target]), complemento([of, the, 'ERK', 'MAPK', cascade, for, 'Th2', cell, differentiation])]). relacion([sujeto(['An']), verbo([enhanced]), complemento(['ubiquitin/proteasome-dependent', degradation, of, 'GATA3', protein, was, observed, in, 'Gfi1(-/-)', 'Th2', 'cells,', and, the, overexpression, of, 'GATA3', eliminated, the, defect, of, 'Th2', cell, function, in, 'Gfi1-deficient', 'Th2', cells])]). relacion([sujeto(['These', data]), verbo([suggest]), complemento([that, the, 'T', cell, 'receptor-mediated', induction, of, 'Gfi1', controls, 'Th2', cell, differentiation, through, the, regulation, of, 'GATA3', protein, stability])]). relacion([sujeto(['Besides', 'T', cell, receptor, 'signaling,', 'IL-12-induced', 'STAT4', and, 'T-bet-', and, 'IL-4-induced', 'STAT6', and, 'GATA3', signaling, pathways, are, the, major, players]), verbo([regulating]), complemento([the, 'Th1', and, 'Th2', differentiation, 'process,', respectively])]). relacion([sujeto(['We', also, showed, that, both, 'GIMAP1', and, 'GIMAP4', genes, are, 'up-regulated', by, 'IL-12', and, other, 'Th1', 'differentiation-inducing', cytokines, in, cells]), verbo([induced]), complemento([to, differentiate, toward, 'Th1', lineage, and, 'down-regulated', by, 'IL-4', in, cells, induced, to, 'Th2'])]). relacion([sujeto(['Our', results, indicate, that, the, 'GIMAP', '(', 'GTPase', of, the, 'immunity-associated', 'protein)', family, of, proteins, is, differentially]), verbo([regulated]), complemento([during, 'Th', cell, differentiation])]). relacion([sujeto(['GATA-3', is, a, transcription, factor, that, is, specifically]), verbo([expressed]), complemento([in, 'T', helper, 2, '(', 'Th2)', cells, and, plays, a, critical, role, in, the, differentiation, of, 'Th2', cells, from, uncommitted, 'CD4+', lymphocytes])]). relacion([sujeto(['In', addition, 'GATA-3', is, essential, for, the, gene, expression, of, the, cytokines, 'IL-4,', 'IL-5', and, 'IL-13', that]), verbo([mediate]), complemento([allergic, inflammation])]). relacion([sujeto(['In', human, 'T', lymphocytes, 'GATA-3', is, normally, localized, to, the, 'cytoplasm,', but, on, activation, by, 'antigen-presenting', cells, via, the, 'T', cell, receptor, '(', 'CD3)', and, 'co-stimulatory', receptor, 'CD28', 'GATA-3', is]), verbo([phosphorylated]), complemento([by, p38, 'MAP', kinase, and, translocates, to, the, nucleus, via, the, nuclear, import, protein, 'importin-alpha'])]). relacion([sujeto(['Corticosteroids']), verbo([bound]), complemento([to, glucocorticoid, receptors, inhibit, 'GATA-3', function, by, competing, for, nuclear, entry, via, 'importin-alpha', and, also, by, inhibiting, p38, 'MAP', kinase, through, the, induction, of, 'MAP', kinase, 'phosphatase-1'])]). relacion([sujeto(['GATA-3', is]), verbo([inhibited]), complemento([by, the, 'Th1', master, regulatory, transcription, 'T-bet', but, in, turn, inhibits, 'STAT-4', and, thus, 'T-bet', so, that, 'Th2', polarization, is, maintained])]). relacion([sujeto(['Since', 'GATA-3', appears, to, be, a, critical, transcription, factor, for, allergic, inflammation, it, is, an, obvious]), verbo([target]), complemento([for, inhibition])]). relacion([sujeto(['Corticosteroids']), verbo([act]), complemento([as, indirect, inhibitors, and, in, patients, with, corticosteroid, resistance, p38, 'MAP', kinase, inhibitors, may, also, prove, to, be, useful, in, the, future])]). relacion([sujeto(['Dlx', homeobox, transcription, factors]), verbo([regulate]), complemento(['epidermal,', neural, and, osteogenic, cellular, differentiation])]). relacion([sujeto(['The', selective, ablation, of, 'Dlx3', in, the, epidermis, results, in, complete, alopecia, owing, to, failure, of, the, hair, shaft, and, inner, root, sheath, to, 'form,', which, is]), verbo([caused]), complemento([by, the, abnormal, differentiation, of, the, cortex])]). relacion([sujeto(['Significantly,', we, elucidate, the, regulatory, cascade, that, positions, 'Dlx3', downstream, of, 'Wnt', signaling, and, as, an, upstream, regulator, of, other, transcription, factors, that]), verbo([regulate]), complemento([hair, follicle, 'differentiation,', such, as, 'Hoxc13', and, 'Gata3'])]). relacion([sujeto(['Moreover,', ablation, of, 'Dlx3', expression, in, the, telogen, bulge, stem, cells, is]), verbo([associated]), complemento([with, a, loss, of, 'BMP', 'signaling,', precluding, 're-initiation', of, the, hair, follicle, growth, cycle])]). relacion([sujeto(['We', describe, the, molecular, mechanisms]), verbo([regulating]), complemento([parathyroid, gland, embryogenesis, and, the, clinical, syndromes, related, to, mutations, in, control, genes])]). relacion([sujeto(['Recent', studies]), verbo([have]), complemento([shown, that, fish, express, parathyroid, hormone])]). relacion([sujeto(['Two', fish, species]), verbo([have]), complemento([been, demonstrated, to, express, parathyroid, hormone, but, the, source, and, physiological, function, of, this, peptide, in, fish, remains, to, be, determined])]). relacion([sujeto(['A', number, of, these, regulatory, factors]), verbo([have]), complemento([been, identified, using, genetically, modified, mouse, models, or, as, genes, causing, human, disease])]). relacion([sujeto(['The', function, of, parathyroid, hormone, and, the, parathyroid, gland, in, humans, is, to]), verbo([regulate]), complemento([serum, calcium, levels, to, maintain, homeostasis])]). relacion([sujeto(['Parathyroid', development, is]), verbo([regulated]), complemento([by, a, cascade, of, 'genes,', which, are, now, being, rapidly, defined, in, mouse, models, and, in, human, mutations])]). relacion([sujeto(['Two', interferon, gamma, '(', 'IFN-gamma)', genes, are]), verbo([expressed]), complemento([in, immune, cells, of, teleost, fish, and, are, potentially, implicated, in, 'B-', and, 'T-lymphocyte', responses])]). relacion([sujeto(['IFN-gamma-2', shows, structural, and, functional, characteristics, to, other, vertebrate, 'IFN-gamma', genes, and, is]), verbo([associated]), complemento([with, 'T-lymphocyte', function])]). relacion([sujeto(['Unexpectedly,', we]), verbo([found]), complemento(['IFN-gamma-1,', which, is, structurally, different, from, 'IFN-gamma-2,', to, be, expressed, in, lipopolysacharide, '(', 'LPS)-stimulated', 'IgM+', '(', 'B-', lymphocyte, 'enriched)', fractions])]). relacion([sujeto(['This', corroborates, a, genuine, 'T-lymphocyte']), verbo([associated]), complemento([role, for, 'IFN-gamma-2'])]). relacion([sujeto(['Measurements', of, different, cytokines, and, chemokines, in, supernatants, of, 'PMBC', cultures, in, the, presence, of, 'PPD', showed]), verbo([increased]), complemento([levels, of, interferon, '(', 'IFN)-gamma', in, active, tuberculosis, infection, '(', 'ATBI)', and, latent, 'TB', infected, '(', 'LTBI)', compared, to, 'controls,', and, increased, levels, of, 'TNF-alpha', in, 'ATBI', compared, with, 'LTBI'])]). relacion([sujeto(['Also,', we]), verbo([found]), complemento([increase, of, 'IL-6', in, cultures, of, 'PPD', positive, and, controls, but, not, in, the, cultures, with, 'Candida'])]). relacion([sujeto(['We', also]), verbo([report]), complemento([the, molecular, signature, of, tuberculosis, 'infection,', in, 'ATBI', 'patients,', the, following, genes, were, found, to, be, 'up-regulated', and, absent, in, 'LTBI', 'individuals:', two, kinases, '(', 'JAK3', and, 'p38MAPK),', four, interleukins, '(', 'IL-7,', 'IL-2,', 'IL-6,', and, 'IFNbeta1),', a, chemokine, '(', 'HCC-4)', a, chemokine, receptor, '(', 'CxCR5),', two, interleukin, receptors, '(', 'IL-1R2', and, 'IL-18R1),', and, three, additional, ones, '(', 'TRAF5,', 'Smad2,', 'CIITA,', and, 'NOS2A)'])]). relacion([sujeto(['Interestingly,', the, majority, of, the, 'up-regulated', genes]), verbo([found]), complemento([in, 'ATBI', were, found, in, cultures, stimulated, with, tuberculin, '(', 'PPD)', or, 'Candida', 'antigens,', suggesting, that, these, pathogens, stimulate, similar, immunological, pathways])]). relacion([sujeto(['We', believe, that, the, molecular, signature, distinguishing, active, from, latent, tuberculosis, infection, may]), verbo([require]), complemento([using, cytokine, bead, arrays, along, with, 'RNA', microarrays, testing, cell, cultures, at, different, times, following, in, vitro, proliferation, assays, using, several, bacterial, antigens, and, 'PPD'])]). relacion([sujeto(['Summary', 'Analysis', of, 'T-helper', cell, differentiation, to, 'T-helper', type, 1, '(', 'Th1)', and, 'Th2', lineages]), verbo([has]), complemento([begun, to, reveal, a, complex, mechanism, whereby, transcription, 'factors,', enzymes, that, either, deposit, or, remove, covalent, modifications, from, histone, tails, and, 'DNA', methylating, enzymes, are, recruited, to, cytokine, genes])]). relacion([sujeto(['Each', resultant, cell, lineage, subsequently, displays, a, programme, of, transcriptional, restrictions, that, 'firstly,', facilitates, expression, of, a, particular, subset, of, signature, cytokines, and, 'secondly,', silences, expression, of, the, cytokines, normally]), verbo([recognized]), complemento([as, being, markers, of, the, opposite, differentiation, limb])]). relacion([sujeto(['Some', essential, proteins, in, this, differentiative, 'paradigm,', such, as, the, transcription, factors, 'GATA3', and, 'T-bet,', are, well, 'studied;', 'however,', the, types, of, enzymatic, activities, that, these, proteins]), verbo([recruit]), complemento([in, order, to, implement, differentiation, are, more, obscure])]). relacion([sujeto(['Recent', 'genome-wide', studies, of, histone, modifications]), verbo([have]), complemento([begun, to, clarify, how, specific, modifications, of, histones, impact, upon, both, transcriptional, regulation, and, chromatin, organization])]). relacion([sujeto(['Here', we, review, how, this, information]), verbo([has]), complemento([enlightened, our, knowledge, of, how, 'Th1/Th2', differentiation, is, orchestrated])]). relacion([sujeto(['Expression', and, immunological, significance, of, 'IFN-gamma,', a, pivotal, cytokine, in, murine, 'lupus,']), verbo([have]), complemento([not, been, clearly, demonstrated, in, human, systemic, lupus, erythematosus, '(', 'SLE)'])]). relacion([sujeto(['Peripheral', blood, 'T', cells, from, patients, with, 'SLE']), verbo([expressed]), complemento([significantly, larger, amounts, of, 'IFN-gamma', in, response, to, stimulation, with, 'anti-CD3', mAb, plus, 'anti-CD28', mAb, than, those, from, normal, controls, as, shown, by, three, analytical, 'methods,', including, 'ELISA,', flow, 'cytometry,', and, quantitative, 'RT-PCR'])]). relacion([sujeto(['The', 'T-box']), verbo([expressed]), complemento([in, 'T', cells, '(', 'T-bet)', 'mRNA/GATA-binding', 'protein-3', '(', 'GATA-3)', mRNA, ratio, was, significantly, higher, in, patients, with, 'SLE', than, in, normal, controls])]). relacion([sujeto(['T', cell, culture, supernatants, from, patients, with, 'SLE', contained, significantly, higher, 'sBLyS-inducing', activity, than, normal, 'controls;', this, was, almost, completely]), verbo([inhibited]), complemento([by, the, addition, of, 'anti-human', 'IFN-gamma', mAb])]). relacion([sujeto(['Taken', 'together,', these, data, strongly, indicate, that, the, overexpression, of, 'IFN-gamma', in, peripheral, blood, 'T', cells, contributes, to, the, immunopathogenesis, of, 'SLE', via, the, induction, of, sBLyS, by, 'monocytes/macrophages,', which, would]), verbo([promote]), complemento(['B', cell, activation, and, maturation])]). relacion([sujeto(['In', this, 'study,', we, attempt, to, determine, whether, lycopene]), verbo([regulates]), complemento([inflammatory, mediators, in, the, ovalbumin, '(', 'OVA)-induced', murine, asthma, model])]). relacion([sujeto(['Additionally,', lycopene, reduced, the]), verbo([increased]), complemento([levels, of, 'GATA-3', mRNA, level, and, 'IL-4', expression, in, 'OVA-challenged', mice])]). relacion([sujeto(['However,', it]), verbo([increased]), complemento(['T-bet', mRNA, level, and, 'IFN-gamma', expression, in, 'lycopene-challenged', mice])]). relacion([sujeto(['These', findings]), verbo([provide]), complemento([new, insight, into, the, immunopharmacological, role, of, lycopene, in, terms, of, its, effects, in, a, murine, model, of, asthma])]). relacion([sujeto(['The', 'GATA', family, of, transcription, factors, '(', 'GATA1-6)']), verbo([binds]), complemento([selected, 'GATA', sites, in, vertebrate, genomes, to, regulate, specific, gene, expression])]). relacion([sujeto(['Although', vertebrate, 'GATA', factors]), verbo([have]), complemento([two, highly, conserved, zinc, finger, 'motifs,', how, the, two, fingers, act, together, to, recognize, functional, 'DNA', elements, is, not, well, understood])]). relacion([sujeto(['Here', we, determined, the, crystal, structures, of, the, 'C-terminal', zinc, finger, of, mouse, 'GATA3']), verbo([bound]), complemento([to, 'DNA', containing, two, variously, arranged, 'GATA', binding, sites])]). relacion([sujeto(['Our', structures, and, accompanying, biochemical, analyses]), verbo([reveal]), complemento([two, distinct, modes, of, 'DNA', binding, by, 'GATA', to, closely, arranged, sites])]). relacion([sujeto(['One', mode]), verbo([involves]), complemento([cooperative, binding, by, two, 'GATA', factors, that, interact, with, each, other, through, 'protein-protein', interactions])]). relacion([sujeto(['The', other]), verbo([involves]), complemento([simultaneous, binding, of, the, 'N-terminal', zinc, finger, '(', 'N-finger)', and, the, 'C-terminal', zinc, finger, of, the, same, 'GATA', factor])]). relacion([sujeto(['Our', studies, represent, the, first, crystallographic, analysis, of, 'GATA', zinc, fingers]), verbo([bound]), complemento([to, 'DNA', and, provide, new, insights, into, the, 'DNA', recognition, mechanism, by, the, 'GATA', zinc, finger])]). relacion([sujeto(['Our', crystal, structure, also]), verbo([reveals]), complemento([a, dimerization, interface, in, 'GATA', that, has, previously, been, shown, to, be, important, for, 'GATA', 'self-association'])]). relacion([sujeto(['These', findings, significantly, advance, our, understanding, of, the, structure, and, function, of, 'GATA', and]), verbo([provide]), complemento([an, important, framework, for, further, investigating, the, in, vivo, mechanisms, of, 'GATA-dependent', gene, regulation])]). relacion([sujeto(['Furthermore,', adoptive, transfer, of, 'T(H)2', cells, with]), verbo([increased]), complemento([or, decreased, levels, of, 'ROG', expression, into, the, asthmatic, mice, resulted, in, reduced, or, enhanced, airway, 'inflammation,', respectively])]). relacion([sujeto(['These', results, indicate, that, 'ROG']), verbo([regulates]), complemento([allergic, airway, inflammation, and, 'AHR', in, a, negative, 'manner,', and, thus, 'ROG', might, represent, another, potential, therapeutic, target, for, the, treatment, of, asthmatic, patients])]). relacion([sujeto(['Aggressive', hepatobiliary, pancreatic, surgery]), verbo([has]), complemento([been, associated, with, high, complication, rates])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, in, patients, with, postoperative, 'infection,', 'Th1/Th2', balance, shifts, toward, 'Th2', dominance, preoperatively])]). relacion([sujeto(['Herein', we, show, that, costimulatory, signals]), verbo([provided]), complemento([by, the, surface, receptor, signaling, lymphocytic, activation, molecule, '(', 'SLAM)', on, myeloid, dendritic, cells, '(', 'mDC)', to, iNKT, cells, is, crucial, for, 'NKT2', orientation])]). relacion([sujeto(['Mature', mDC, of, 'C57BL/6', mice]), verbo([express]), complemento(['SLAM', and, induce, 'C57BL/6', or, 'NOD', iNKT, cells, to, acquire, a, predominant, 'NKT2', cytokine, phenotype, in, response, to, antigenic, stimulation, with, the, iNKT, 'cell-specific', 'Ag,', the, 'alpha-galactosylceramide'])]). relacion([sujeto(['In', 'contrast,', mature, 'NOD', mDC]), verbo([express]), complemento([significantly, lower, levels, of, 'SLAM', and, are, unable, to, promote, 'GATA-3', '(', the, 'SLAM-induced', intracellular, 'signal)', 'up-regulation', and, 'IL-4/IL-10', production, in, iNKT, cells, from, 'NOD', or, 'C57BL/6', mice])]). relacion([sujeto(['NOD', mice, carry, a, genetic, defect, of, the, 'Slamf1', gene, that, is]), verbo([associated]), complemento([with, reduced, 'SLAM', expression, on, 'double-positive', thymocytes, and, altered, iNKT, cell, development, in, the, thymus])]). relacion([sujeto(['Our', data]), verbo([suggest]), complemento([that, the, genetic, 'Slamf1', defect, in, 'NOD', mice, also, affects, 'SLAM', expression, on, other, immune, cells, such, as, the, 'mDC,', thus, critically, impairing, the, peripheral, differentiation, of, iNKT, cells, toward, a, regulatory, 'NKT2', type])]). relacion([sujeto(['The', transcription, factor, 'GATA3']), verbo([has]), complemento([recently, been, found, to, be, involved, in, the, carcinogenesis, for, numerous, cancers])]). relacion([sujeto(['Positive', 'GATA3', expression, in, hysterectomy, specimens, significantly, correlated, to, high, 'International', 'Federation', of, 'Gynecology', and, 'Obstetrics', 'stage,', serous, 'papillary/clear', cell, 'subtypes,', high, histologic, 'grade,']), verbo([loss]), complemento([of, 'PR', 'expression,', 'aneuploidy,', high, 'proliferation,', pathologic, p53, and, p16, 'expression,', and, poor, prognosis, '(', 'P', =])]). relacion([sujeto(['GATA3', expression, is]), verbo([associated]), complemento([with, an, aggressive, phenotype, and, adds, independent, prognostic, information, in, addition, to, receptor, status])]). relacion([sujeto(['We']), verbo([have]), complemento([found, that, 'YM-341619', 'hydrochloride,', which, suppressed, 'IL-4-induced', 'STAT6-dependent', reporter, gene, 'expression,', inhibited, the, differentiation, of, mouse, spleen, 'T', cells, into, 'Th2', cells, in, vitro])]). relacion([sujeto(['YM-341619']), verbo([suppressed]), complemento([the, production, of, 'IL-4', and, the, expression, of, 'GATA-3', 'mRNA,', a, 'Th2', transcription, 'factor,', in, 'T', cells, cultured, with, 'anti-CD3', antibody, and, 'anti-CD28', antibody, in, the, presence, of, 'IL-4'])]). relacion([sujeto(['YM-341619']), verbo([suppressed]), complemento(['IL-4', and, 'IL-13', production, in, the, splenocytes, of, these, 'DNP-Ascaris-sensitized', rats, without, augmenting, 'IFN-gamma', production])]). relacion([sujeto(['YM-341619', also, 'dose-dependently']), verbo([suppressed]), complemento([eosinophil, accumulation, in, the, lung, '(', 0.003, -, 3, 'mg/kg,', p])]). relacion([sujeto([')']), verbo([induced]), complemento([by, repeated, exposure, to, ovalbumin, in, 'ovalbumin-sensitized', rats])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, 'YM-341619', has, the, ability, to, suppress, 'allergen-induced', 'Th2', responses, by, selectively, inhibiting, the, differentiation, of, 'CD4(+)', 'T', cells, into, the, 'Th2', subset])]). relacion([sujeto([3, is]), verbo([expressed]), complemento([in, hindbrain, 'V2', interneurons, that, 'co-express', 'Nkx6'])]). relacion([sujeto([1, ',']), verbo([suggesting]), complemento([the, possibility, of, functional, redundancy])]). relacion([sujeto(['Here,', we]), verbo([report]), complemento([that, 'Nkx6'])]). relacion([sujeto([3, null, embryonic, mouse, hindbrain, did, not]), verbo([reveal]), complemento([detectable, defects, in, progenitor, 'markers,', motor, neuron, or, 'V2', interneuron, 'sub-types'])]). relacion([sujeto([1]), verbo([promote]), complemento(['V2', interneuron, differentiation, in, the, developing, chick, hindbrain])]). relacion([sujeto([3, function, is, dispensable, for, 'CNS', development, and]), verbo([lead]), complemento([to, the, proposal, that, absence, of, overt, defects, is, due, to, functional, compensation, from, a, related, homeodomain, transcription, factor])]). relacion([sujeto(['No', baseline, differences, were, present, between, the]), verbo([responder]), complemento(['groups,', but, fast, responders, had, significantly, higher, 'IL-4', transcripts, than, slow, responders, at, week, 1])]). relacion([sujeto(['Only', slow, responders, also, showed, a, significant]), verbo([decrease]), complemento([in, 'IL-4', expression, at, week, 1])]). relacion([sujeto(['Inflammatory', bowel, diseases, '(', 'IBD)', are, inflammatory, diseases, with, a, multifactorial, component, that]), verbo([involve]), complemento([the, intestinal, tract])]). relacion([sujeto(['One', factor]), verbo([involved]), complemento([in, 'IBD', development, is, a, genetic, 'predisposition,', associated, to, 'NOD2/CARD15', and, 'Toll-like', receptor, 4, '(', 'TLR4)', polymorphisms, that, might, favor, infectious, enterocolitis, that, is, possibly, associated, to, the, development, of, 'IBD'])]). relacion([sujeto(['The', role, of, intra, and, extracellular, 'molecules,', such, as, transcription, factors, and, cytokines, that, are]), verbo([involved]), complemento([in, the, inflammatory, 'response,', needs, to, be, understood])]). relacion([sujeto(['The', relevance, of, immunologic, molecules, that, might, drive, the, immune, response, to, a, 'T', helper, '(', 'Th)', 1, ',', 'Th', 2, or, the, recently, described, 'Th', 17, 'phenotype,']), verbo([has]), complemento([been, demonstrated, in, animal, models, and, clinical, studies, with, 'IBD', patients])]). relacion([sujeto(['Recently,', an, association, between, 'CD', and, 'Th', 17]), verbo([has]), complemento([been, reported])]). relacion([sujeto(['Although', the, molecular]), verbo([targets]), complemento([remain, 'unidentified,', the, broad, activity, of, select, 'IMiDs', immunomodulatory, drugs, on, cell, signaling, pathways, and, transcription, regulation, has, been, partly, described])]). relacion([sujeto(['One', characteristic, of, these, compounds, is, their, ability, to]), verbo([act]), complemento([as, a, 'co-stimulus', of, 'TCR', ligation, leading, to, increased, 'IL-2,', 'TNF-alpha', and, 'IFN-gamma', expression, indicative, of, a, 'Th1', phenotype])]). relacion([sujeto(['Because', clinical, evidence, for, this, response]), verbo([has]), complemento([been, observed, in, thalidomide, and, lenalidomide, treated, 'patients,', we, investigated, the, effect, of, 'CC-4047', on, 'T', cell, activation, and, differentiation, at, the, molecular, level])]). relacion([sujeto(['We', used, primary, human, 'CD4(+)', 'T', cells, as, a, model, and]), verbo([found]), complemento([that, 'CC-4047', enhances, the, expression, of, transcription, factor, 'T-bet', in, both, naive, and, 'pre-polarized', 'Th2', cells])]). relacion([sujeto(['This', modulation]), verbo([leads]), complemento([to, upregulation, of, 'Th1', markers, and, cytokine, production])]). relacion([sujeto(['By']), verbo([increasing]), complemento([the, expression, of, 'T-bet,', 'CC-4047', promotes, the, differentiation, of, naive, 'T-cells', to, 'Th1', as, well, as, effectively, reverting, 'Th2', cells, into, 'Th1-like', effector, cells, in, vitro])]). relacion([sujeto(['These', findings, elucidate, a, novel, mechanism, of, action, of, 'CC-4047', on, 'T', cell, 'differentiation,']), verbo([suggesting]), complemento([that, certain, 'IMiDs', immunomodulatory, drugs, may, have, expanded, clinical, application, in, treating, both, allergic, diseases, and, certain, 'T', cell, lymphomas, where, a, predominant, 'Th2', phenotype, is, displayed])]). relacion([sujeto(['GATA']), verbo([binding]), complemento([protein, 3, '(', 'GATA3)', is, an, important, regulator, of, central, nervous, system, '(', 'CNS)', 'development,', but, its, expression, pattern, in, the, postnatal, 'CNS', has, not, been, studied])]). relacion([sujeto(['During', the, first, 2, weeks, of, postnatal, 'development,', numerous, 'GATA3-expressing', cells, were]), verbo([found]), complemento([in, the, intergeniculate, 'leaf,', ventral, lateral, geniculate, 'nucleus,', pretectal, 'nucleus,', nucleus, of, the, posterior, 'commissure,', superior, 'colliculus,', inferior, 'colliculus,', periaqueductal, 'grey,', substantia, nigra, and, raphe, nuclei])]). relacion([sujeto(['As', postnatal, development, 'progressed,', 'however,', 'GATA3', expression, 'weakened,', and, was]), verbo([maintained]), complemento([in, only, a, few, regions, of, the, adult, 'CNS'])]). relacion([sujeto(['Throughout', the, 'brain,', we]), verbo([found]), complemento([that, 'GATA3-expressing', cells, were, 'NeuN-positive,', and, no, colocalization, with, glial, fibrillary, acidic, protein, '(', 'GFAP)', was, observed])]). relacion([sujeto(['In', the, substantia, 'nigra,', 'GATA3', was, exclusively]), verbo([expressed]), complemento([in, cells, of, the, reticulate, part, and, some, of, which, were, found, to, be, 'GABAergic'])]). relacion([sujeto(['This', study, presents, a, comprehensive, overview, of, 'GATA3', expression, in, the, 'CNS', throughout, postnatal, 'life,', and, the, dynamics, that, we, observed]), verbo([provide]), complemento([insights, for, further, investigations, of, the, roles, of, 'GATA3', in, postnatal, development, and, the, maintenance, of, the, mature, 'CNS'])]). relacion([sujeto(['The', immune, response, to, allergens, starts, with, stimulation, of, a, naïve, 'T', helper, '(', 'Th)', cell, and, its, differentiation, into, a, 'Th2', 'cell,']), verbo([expressing]), complemento([the, cytokines, interleukin, '(', 'IL)-4,', 'IL-5', and, 'IL-13', responsible, for, the, allergic, response])]). relacion([sujeto(['The', initial, pattern, of, cytokine, expression, is]), verbo([retained]), complemento([during, restimulation, and, division, of, the, 'Th2', cell, to, create, a, population, of, specific, 'allergen-responsive', memory, 'Th2', cells])]). relacion([sujeto(['Th2-specific', changes, in, chromatin, configuration, at, the, 'Th2', locus]), verbo([act]), complemento([locally, to, open, 'DNA,', allowing, recruitment, of, transcriptional, machinery, and, rapid, induction, of, cytokine, expression])]). relacion([sujeto(['Loss', of, 'DNA', methylation, at, the, 'Th2', locus, during, differentiation, from, a, naïve, 'Th', cell, correlates, to]), verbo([increased]), complemento([histone, 'acetylation,', consistent, with, the, expression, of, 'IL-4,', 'IL-5', and, 'IL-13'])]). relacion([sujeto(['The', silencing, of, the, 'Th2', locus, in, 'Th1', cells, was]), verbo([associated]), complemento([with, repressive, histone, methylation])]). relacion([sujeto(['Chromosomal', localization, of, nine, porcine, genes, encoding, transcription, factors]), verbo([involved]), complemento([in, adipogenesis, was, determined])]). relacion([sujeto(['The', transcription, factor, 'GATA3']), verbo([has]), complemento([recently, been, shown, to, be, necessary, for, mammary, gland, morphogenesis, and, luminal, cell, differentiation])]). relacion([sujeto(['There', is, also, an]), verbo([increasing]), complemento([body, of, data, linking, 'GATA3', to, the, estrogen, receptor, alpha, '(', 'ERalpha)', pathway])]). relacion([sujeto(['Among', these, it, was, shown, that, 'GATA3']), verbo([associates]), complemento([with, the, promoter, of, the, 'ERalpha', gene, and, 'ERalpha', can, reciprocally, associate, with, the, 'GATA3', gene])]). relacion([sujeto(['GATA3']), verbo([has]), complemento([also, been, directly, implicated, in, a, differentiated, phenotype, in, mouse, models, of, mammary, tumourigenesis])]). relacion([sujeto(['We']), verbo([have]), complemento([used, a, newly, described, method, of, 'meta-analysis', of, multiple, cancer, studies, within, the, 'Oncomine', 'database,', focusing, here, predominantly, upon, breast, cancer, studies])]). relacion([sujeto(['We', demonstrate, that, 'ERalpha', and, 'GATA3', reciprocally]), verbo([have]), complemento([the, highest, overlap, with, one, another])]). relacion([sujeto(['An', exceptionally, high, 'B19V', viral, load, in, 'EMBs', '(', 115, ',', 91, viral, 'copies/mug', nucleic, 'acids),', peripheral, blood, mononuclear, cells, '(', 'PBMCs)', and, serum, was, measured, in, a, 'DCMi', patient, at, initial, 'presentation,']), verbo([suggesting]), complemento(['B19V', viremia])]). relacion([sujeto(['The', 'B19V', viral, load, in, 'EMBs', had]), verbo([decreased]), complemento([substantially, 6, and, 12, months, 'afterwards,', and, was, not, traceable, in, 'PBMCs', and, the, serum, at, these, times])]). relacion([sujeto(['Real-time', 'RT-PCR', of, 'IFNgamma', 'secretion-assay-enriched', 'T-cells']), verbo([responding]), complemento([to, the, 'peptides,', 'SALKLAIYKA', and, 'GLCPHCINVG,', revealed, a, disproportionately, high, 'T-cell', receptor, 'Vbeta', '(', 'TRBV)', 11, expression, in, this, population])]). relacion([sujeto(['Our', results, indicate, that, 'B19V', 'Ag-specific', 'CD8(+)', 'T-cells', with, effector, function, are]), verbo([involved]), complemento([in, 'B19V', associated, 'DCMi'])]). relacion([sujeto(['In', 'particular,', a, dominant, role, of, 'TRBV11', and, 'type-1/CTL', effector, cells, in, the, 'T-cell']), verbo([mediated]), complemento([antiviral, immune, response, is, suggested])]). relacion([sujeto(['Th2', cell, identity, is]), verbo([maintained]), complemento([in, memory, 'Th2', cells])]). relacion([sujeto(['Significant', advances, in, understanding, of, the, molecular, requirement, for, these, processes]), verbo([have]), complemento([been, made])]). relacion([sujeto(['The', expression, of, 'GATA3,', a, master, transcription, factor, for, 'Th2', cell, 'differentiation,', is, uniquely]), verbo([regulated]), complemento([by, several, distinct, mechanisms])]). relacion([sujeto(['Molecular', analyses, of, memory, 'Th2', cells, revealed, that, cell, survival, and, the, maintenance, of, 'Th2', cell, function, are, epigenetically]), verbo([regulated]), complemento([by, various, nuclear, 'factors,', including, 'Polycomb', and, 'Trithorax', molecules])]). relacion([sujeto(['Neural', 'crest-derived', structures, that, depend, critically, upon, expression, of, the, basic, 'helix-loop-helix', 'DNA']), verbo([binding]), complemento([protein, 'Hand2', for, normal, development, include, craniofacial, cartilage, and, 'bone,', the, outflow, tract, of, the, 'heart,', cardiac, 'cushion,', and, noradrenergic, sympathetic, ganglion, neurons])]). relacion([sujeto(['We']), verbo([have]), complemento([overcome, this, difficulty, by, specific, deletion, of, 'Hand2', in, neural, 'crest-derived', cells, by, crossing, our, line, of, floxed, 'Hand2', mice, with, 'Wnt1-Cre', transgenic, mice])]). relacion([sujeto(['Our', analysis, of, 'Hand2', 'knock-out', in, neural, 'crest-derived', cells]), verbo([reveals]), complemento([effects, on, development, in, all, neural, 'crest-derived', structures, where, 'Hand2', is, expressed])]). relacion([sujeto(['In', the, autonomic, nervous, 'system,', conditional, disruption, of, 'Hand2', results, in, a, significant, and, progressive]), verbo([loss]), complemento([of, neurons, as, well, as, a, significant, loss, of, 'TH', expression])]). relacion([sujeto(['Hand2', affects, generation, of, the, neural, precursor, pool, of, cells, by, affecting, both, the, proliferative, capacity, of, the, progenitors, as, well, as, affecting, expression, of, 'Phox2a', and, 'Gata3,', 'DNA']), verbo([binding]), complemento([proteins, important, for, the, cell, autonomous, development, of, noradrenergic, neurons])]). relacion([sujeto(['Our', data]), verbo([suggest]), complemento([that, 'Hand2', is, a, multifunctional, 'DNA', binding, protein, affecting, differentiation, and, cell, 'type-specific', gene, expression, in, neural, 'crest-derived', noradrenergic, sympathetic, ganglion, neurons])]). relacion([sujeto(['Hand2']), verbo([has]), complemento([a, pivotal, function, in, a, 'non-linear', 'cross-regulatory', network, of, 'DNA', binding, proteins, that, affect, cell, autonomous, control, of, differentiation, and, cell, 'type-specific', gene, expression])]). relacion([sujeto(['Supervised', analysis, was, used, to, identify, genes, differentially]), verbo([expressed]), complemento([between, normal, prostate, and, seminal, 'vesicle,', and, this, list, was, then, 'cross-referenced', to, genes, differentially, expressed, between, normal, and, cancerous, prostate])]). relacion([sujeto(['Among', these, genes, was, the, known, candidate, prostate, tumor, suppressor, 'GSTP1', '(']), verbo([involved]), complemento([in, xenobiotic, 'detoxification)'])]). relacion([sujeto(['Such', genes, and, their, pathways, may, inform, mechanisms, of, prostate, 'carcinogenesis,', and]), verbo([suggest]), complemento([new, opportunities, for, prostate, cancer, prevention])]). relacion([sujeto(['Mast', cells, are, thought, to]), verbo([participate]), complemento([in, a, wide, variety, of, pathophysiological, conditions])]). relacion([sujeto(['Mast', cell, developmental, process, is, likely, to, be, profoundly, affected, by, 'cell-autonomous', transcriptional, regulators, such, as, the, 'GATA', family, and, 'CCAAT/enhancer']), verbo([binding]), complemento([protein, '(', 'C/EBP)', family, members])]). relacion([sujeto(['Extracellular', regulators, such, as, stem, cell, factor, and, 'IL-3']), verbo([have]), complemento([essential, roles, in, basal, and, inducible, mast, cell, 'generation,', respectively])]). relacion([sujeto(['The', 'relationship,', 'however,', between, the, extracellular, signaling, and, cellular, transcriptional, control, is, 'unclear,', and, the]), verbo([trigger]), complemento([of, the, mast, cell, development, remains, elusive])]). relacion([sujeto(['NK', cells]), verbo([have]), complemento([been, long, time, considered, as, cytotoxic, lymphocytes, competent, in, killing, 'virus-infected', cells, and, tumors])]). relacion([sujeto(['In', this, 'context,', the, real, existence, of, a, defined, 'NK', subset, with, negative, regulatory, properties]), verbo([has]), complemento([been, hypothesized, but, never, clearly, demonstrated])]). relacion([sujeto(['Through', these, 'factors,', 'NK-ireg', cells]), verbo([act]), complemento([as, effectors, of, the, 'down-regulation', of, the, immune, 'response:', reconverting, mature, myeloid, 'DC', '(', 'mDC)', into, 'immature/tolerogenic', 'DC,', blocking, cytolytic, functions, on, conventional, 'NK', cells, and, inducing, 'HLA-G', membrane, expression, on, 'PB-derived', monocytes])]). relacion([sujeto(['The', generation, of, &, 'quot;NK-ireg"', cells, is, 'obtained,', by, 'default,', in, culture, conditions, favouring, 'cell-to-cell', 'contacts,', and, it, is, strictly, dependent, on, reciprocal, 'trans-presentation', of, 'membrane-bound', 'IL-15', forms, constitutively, and, selectively]), verbo([expressed]), complemento([by, human, 'CD34(+)', 'PB-HP'])]). relacion([sujeto(['Finally,', a, small, subset, of, 'NKp46(+)', 'HLA-G(+)', 'IL-10(+)', is, detected, within, freshly, isolated, decidual, 'NK', 'cells,']), verbo([suggesting]), complemento([that, these, cells, could, represent, an, in, vivo, counterpart, of, the, 'NK-ireg', cells])]). relacion([sujeto(['CD43', is, a, highly, glycosylated, transmembrane, protein, that]), verbo([regulates]), complemento(['T', cell, activation])]). relacion([sujeto(['CD43(-/-)', 'T', cells, are, hyperproliferative, and, the, cytoplasmic, tail, of, 'CD43']), verbo([has]), complemento([been, found, to, be, sufficient, to, reconstitute, 'wild-type', proliferation, 'levels,', suggesting, an, intracellular, mechanism])]). relacion([sujeto(['In', this, 'study,', we]), verbo([report]), complemento([that, upon, 'TCR', ligation, 'CD43(-/-)', 'T', cells, demonstrated, no, increase, in, tyrosine, phosphorylation, but, a, decreased, calcium, flux])]). relacion([sujeto(['Interestingly,', 'CD43(-/-)', 'T', cells, preferentially, differentiated, into, 'Th2', cells, in, 'vitro,', and, 'CD43(-/-)', 'T', cells, show]), verbo([increased]), complemento(['GATA-3', translocation, into, the, nucleus])]). relacion([sujeto(['In', 'vivo,', 'CD43(-/-)', mice, exhibited]), verbo([increased]), complemento([inflammation, in, two, separate, models, of, 'Th2-mediated', allergic, airway, disease])]). relacion([sujeto(['Nonetheless,', the, 'CD43(-/-)', mice, produced, more, 'IL-5', when, restimulated, with, 'MOG(35-55)', in, vitro, and, demonstrated]), verbo([decreased]), complemento(['delayed-type', hypersensitivity, responses])]). relacion([sujeto(['Gata', transcription, factors, are, critical, regulators, of, proliferation, and, differentiation, implicated, in, various, human, 'cancers,', but, specific, genes]), verbo([activated]), complemento([by, 'Gata', proteins, remain, to, be, identified])]). relacion([sujeto(['We', previously]), verbo([reported]), complemento([that, enforced, expression, of, 'Gata3', during, 'T', cell, development, in, 'CD2-Gata3', transgenic, mice, induced, 'CD4(+)CD8(+)', 'double-positive', '(', 'DP)', 'T', cell, lymphoma])]). relacion([sujeto([10, 'T-cell', receptor, 'transgene,', which, directs, 'DP', cells, towards, the, 'CD4', 'lineage,', resulted, in]), verbo([enhanced]), complemento([lymphoma, development, and, a, dramatic, increase, in, thymocyte, cell, size, in, 'CD2-Gata3', transgenic, mice])]). relacion([sujeto(['CD2-Gata3', 'DP', cells]), verbo([expressed]), complemento([high, levels, of, the, 'proto-oncogene', 'c-Myc', but, the, 'Notch1', signaling, 'pathway,', which, is, known, to, induce, 'c-Myc,', was, not, activated])]). relacion([sujeto(['Gene', expression, profiling, showed, that, in, 'CD2-Gata3', lymphoma, cells, transcription, of, 'c-Myc', and, its]), verbo([target]), complemento([genes, was, further, increased])]). relacion([sujeto(['A', substantial, fraction, of, 'CD2-Gata3', lymphomas, had, trisomy, of, chromosome, 15, ',']), verbo([leading]), complemento([to, an, increased, 'c-Myc', gene, dose])]). relacion([sujeto(['Interestingly,', most, lymphomas, showed, high, expression, of, the, 'Notch']), verbo([targets]), complemento(['Deltex1', and, 'Hes1,', often, due, to, activating, 'Notch1', 'PEST', domain, mutations])]). relacion([sujeto(['The']), verbo([finding]), complemento([that, 'Gata3', regulates, 'c-Myc', expression, 'levels,', in, a, direct, or, indirect, 'fashion,', may, explain, the, parallel, phenotypes, of, mice, with, overexpression, or, deficiency, of, either, of, the, two, transcription, factors])]). relacion([sujeto(['The', 'HMG-box', domain, of, 'LEF-1', and, two, zinc, finger, domains, of, 'GATA-3', were]), verbo([found]), complemento([to, be, important, for, the, physical, association])]). relacion([sujeto(['Moreover,', 'LEF-1']), verbo([inhibited]), complemento([the, binding, activity, of, 'GATA-3', to, the, interleukin, '(', 'IL)-5', promoter])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, 'LEF-1', is, involved, in, the, 'GATA-3', 'complex,', while, also, regulating, the, 'GATA-3', 'function,', such, as, the, induction, of, 'Th2', cytokine, expression, via, the, inhibition, of, the, 'DNA-binding', activity, of, 'GATA-3'])]). relacion([sujeto(['Gene', expression, profiling, of, human, cancer]), verbo([has]), complemento([allowed, for, a, unique, insight, into, the, genes, that, are, involved, in, these, processes])]). relacion([sujeto(['Thus,', we]), verbo([have]), complemento([attempted, to, utilize, this, approach, through, the, analysis, of, a, series, of, 'primary,', 'non-metastatic', cutaneous, tumors, and, metastatic, melanoma, samples])]). relacion([sujeto(['We']), verbo([have]), complemento([utilized, gene, microarray, analysis, and, a, variety, of, molecular, techniques, to, compare, 40, metastatic, melanoma, '(', 'MM)', 'samples,', composed, of, 22, 'bulky,', macroscopic, '(', 'replaced)', lymph, node, 'metastases,', 16, subcutaneous, and, 2, distant, metastases, '(', adrenal, and, 'brain),', to, 42, primary, cutaneous, 'cancers,', comprised, of, 16, 'melanoma,', 11, squamous, 'cell,', 15, basal, cell, skin, cancers])]). relacion([sujeto(['We']), verbo([find]), complemento([that, primary, basal, cell, 'carcinomas,', squamous, cell, carcinomas, and, thin, melanomas, express, dramatically, higher, levels, of, many, 'genes,', including, 'SPRR1A/B,', 'KRT16/17,', 'CD24,', 'LOR,', 'GATA3,', 'MUC15,', and, 'TMPRSS4,', than, metastatic, melanoma])]). relacion([sujeto(['In', 'contrast,', the, metastatic, melanomas]), verbo([express]), complemento([higher, levels, of, genes, such, as, 'MAGE,', 'GPR19,', 'BCL2A1,', 'MMP14,', 'SOX5,', 'BUB1,', 'RGS20,', and, more])]). relacion([sujeto(['We', further, evaluated, primary, melanomas, of, varying, 'Breslow\'s', tumor, thickness, to, determine, that, the, transition, in, expression, occurs, at, different, thicknesses, for, different, genes]), verbo([suggesting]), complemento([that, the, &, 'quot;transition', 'zone"', represents, a, critical, time, for, the, emergence, of, the, metastatic, phenotype])]). relacion([sujeto(['These', are, strong, candidates, for, genes]), verbo([involved]), complemento([in, the, progression, or, suppression, of, the, metastatic, phenotype])]). relacion([sujeto(['The', gene, expression, profiling, of, 'primary,', 'non-metastatic', cutaneous, tumors, and, metastatic, melanoma]), verbo([has]), complemento([resulted, in, the, identification, of, several, genes, that, may, be, centrally, involved, in, the, progression, and, metastatic, potential, of, melanoma])]). relacion([sujeto(['This']), verbo([has]), complemento([very, important, implications, as, we, continue, to, develop, an, improved, understanding, of, the, metastatic, 'process,', allowing, us, to, identify, specific, genes, for, prognostic, markers, and, possibly, for, targeted, therapeutic, approaches])]). relacion([sujeto(['We', demonstrate, for, the, first, time, a]), verbo([decreased]), complemento(['FOXP3', expression, accompanied, by, an, upregulation, of, 'T-bet', and, 'GATA-3', and, a, downregulation, of, 'TGF-beta1', in, 'CRSwNP', versus, controls, and, 'CRSsNP'])]). relacion([sujeto(['Atopic', eczema, is, characterized, by, 'Th2-dominant', immunity, with, the, cytokine, interleukin, 13, and, the, transcription, factor, 'GATA']), verbo([binding]), complemento([protein, 3, playing, a, critical, role])]). relacion([sujeto(['IL13', was, not]), verbo([associated]), complemento([with, childhood, eczema])]). relacion([sujeto(['For', 'GATA3,', the, single, nucleotide, polymorphism, '(', 'SNP)', rs2275806, '(', promoter, 'region)', showed, an]), verbo([increased]), complemento([odds, ratio, for, atopic, eczema, independent, of, whether, the, comparison, group, had, a, positive, skin, prick, test])]). relacion([sujeto(['The', 'SNP', rs444762, '(', intron, 3, 'region)', was]), verbo([associated]), complemento([with, atopic, eczema, in, comparison, with, children, without, eczema])]). relacion([sujeto(['The']), verbo([increased]), complemento([relative, risks, remained, significant, after, adjustment, for, multiple, testing, only, for, rs2275806, '(', 'P', &, 'lt;', 0.05, ')'])]). relacion([sujeto(['A', 'SNP', in, 'GATA3', is]), verbo([associated]), complemento([with, atopic, eczema])]). relacion([sujeto(['This']), verbo([finding]), complemento([highlights, the, importance, of, 'GATA3', as, an, 'immune-modulating', gene, in, atopic, eczema])]). relacion([sujeto(['Angular', head, movements, in, vertebrates, are, detected, by, the, three, semicircular, canals, of, the, inner, ear, and, their]), verbo([associated]), complemento([sensory, 'tissues,', the, cristae])]). relacion([sujeto(['Bone', morphogenetic, protein, 4, '(', 'Bmp4),', a, member, of, the, 'Transforming', growth, factor, family, '(', 'TGF-beta),', is, conservatively]), verbo([expressed]), complemento([in, the, developing, cristae, in, several, 'species,', including, 'zebrafish,', 'frog,', 'chicken,', and, mouse])]). relacion([sujeto(['Using', mouse, models, in, which, 'Bmp4', is, conditionally, deleted, within, the, inner, 'ear,', as, well, as, chicken, models, in, which, 'Bmp', signaling, is, knocked, down, specifically, in, the, 'cristae,', we, show, that, 'Bmp4', is, essential, for, the, formation, of, all, three, cristae, and, their]), verbo([associated]), complemento([canals])]). relacion([sujeto(['Our', results, indicate, that, 'Bmp4', does, not]), verbo([mediate]), complemento([the, formation, of, sensory, hair, and, supporting, cells, within, the, cristae, by, directly, regulating, genes, required, for, prosensory, development, in, the, inner, ear, such, as, 'Serrate1', '(', 'Jagged1', in, 'mouse),', 'Fgf10,', and, 'Sox2'])]). relacion([sujeto(['Instead,', 'Bmp4', most, likely]), verbo([mediates]), complemento([crista, formation, by, regulating, 'Lmo4', and, 'Msx1', in, the, sensory, region, and, 'Gata3,', 'p75Ngfr,', and, 'Lmo4', in, the, 'non-sensory', region, of, the, 'crista,', the, septum, cruciatum])]). relacion([sujeto(['In', the, 'canals,', 'Bmp2', and, 'Dlx5', are]), verbo([regulated]), complemento([by, 'Bmp4,', either, directly, or, indirectly])]). relacion([sujeto(['Mechanisms']), verbo([involved]), complemento([in, the, formation, of, sensory, organs, of, the, vertebrate, inner, ear, are, thought, to, be, analogous, to, those, regulating, sensory, bristle, formation, in, 'Drosophila'])]). relacion([sujeto(['Our', results]), verbo([suggest]), complemento(['that,', in, comparison, to, sensory, 'bristles,', crista, formation, within, the, inner, ear, requires, an, additional, step, of, sensory, and, 'non-sensory', fate, specification])]). relacion([sujeto(['The', inflammatory, response, observed, in, allergic, disease]), verbo([involves]), complemento([multiple, cell, types, but, is, orchestrated, in, part, by, the, 'T(H)2', cytokines, 'IL-4,', 'IL-5,', and, 'IL-13'])]). relacion([sujeto(['In', recent, 'years,', the, transcription, factors, that, control, the, expression, and, function, of, these, cytokines]), verbo([have]), complemento([been, 'elucidated,', including, signal, transducer, and, activator, of, transcription, 6, ',', 'GATA3,', nuclear, factor, of, activated, 'T', 'cells,', and, nuclear, factor, kappaB])]). relacion([sujeto(['These', molecules, are, attractive]), verbo([targets]), complemento([for, therapeutic, intervention, because, they, regulate, the, expression, of, numerous, effector, molecules, and, functions, simultaneously])]). relacion([sujeto(['In', this, review, we, examine, the, role, of, each, transcription, factor, in, allergic, disease, and, discuss, approaches, that]), verbo([have]), complemento([been, taken, to, therapeutically, interfere, with, transcription, factor, function, in, allergic, disease])]). relacion([sujeto(['CBFbeta', is, the, 'non-DNA']), verbo([binding]), complemento([subunit, of, the, core, binding, factors, '(', 'CBFs)'])]). relacion([sujeto(['Here', we, show, that, 'CBFbeta', is, also]), verbo([required]), complemento([at, very, early, stages, of, natural, killer, '(', 'NK)-cell', development])]). relacion([sujeto(['Therefore,', the, ability, of, the, prethymic, cell, to]), verbo([respond]), complemento([appropriately, to, 'Notch', is, dependent, on, 'CBFbeta,', and, both, signals, converge, to, activate, the, 'T-cell', developmental, program])]). relacion([sujeto(['On', the, other, 'hand,', 'Notch', signaling, is, sufficient, for, blockage, of, 'B', cell, development, without, 'GATA3,']), verbo([suggesting]), complemento([that, 'T', cell, fate, specification, at, the, branching, point, does, not, result, simply, from, the, developmental, arrest, of, 'B', cell, lineage, by, 'Notch', signaling])]). relacion([sujeto(['The', 'Brn-3', family, of, transcription, factors, play, a, critical, role, in]), verbo([regulating]), complemento([expression, of, genes, that, control, cell, 'fate,', including, the, small, heat, shock, protein, 'Hsp27'])]). relacion([sujeto([5, ')', in, the, mouse, 'heart,', with, significant]), verbo([increases]), complemento([seen, later, during, development])]). relacion([sujeto(['An']), verbo([increase]), complemento([in, expression, of, the, long, 'Brn-3a(l)', isoform, between, 'E17', and, adult, coincided, with, a, decrease, in, expression, of, 'Brn-3b(l)', and, a, marked, increase, in, expression, of, 'Hsp27'])]). relacion([sujeto(['Loss', of, 'Brn-3a', was, correlated, with, a, compensatory]), verbo([increase]), complemento([in, 'Brn-3b', and, 'GATA3', mRNA, but, no, change, in, 'Hsp27', mRNA])]). relacion([sujeto(['Reporter', assays, in, isolated, cardiomyocytes, demonstrated, that, both, 'Brn-3a', and, 'Brn-3b']), verbo([activate]), complemento([the, hsp27, promoter, via, a, consensus, 'Brn-3-binding', site])]). relacion([sujeto(['GATA-3', was, identified, in, a, microarray, screen, of, the, mouse, mammary, gland, as, the, most, highly]), verbo([expressed]), complemento([transcription, factor, in, the, mammary, epithelium, and, is, expressed, exclusively, in, the, luminal, epithelial, cell, population])]). relacion([sujeto(['Targeted', deletion, of, 'GATA-3', in, mammary, glands]), verbo([leads]), complemento([to, profound, defects, in, mammary, development, and, inability, to, specify, and, maintain, the, luminal, cell, fate, in, the, adult, mouse])]). relacion([sujeto(['In', breast, 'cancer,', 'GATA-3']), verbo([has]), complemento([emerged, as, a, strong, predictor, of, tumor, 'differentiation,', 'estrogen-receptor', 'status,', and, clinical, outcome])]). relacion([sujeto(['GATA-3']), verbo([maintains]), complemento([tumor, differentiation, and, suppresses, tumor, dissemination, in, a, mouse, model, of, breast, cancer])]). relacion([sujeto(['GATA-3', is, a, zinc, finger, transcription, factor, that, is]), verbo([expressed]), complemento([in, 'T', cell, lineages, as, well, as, in, the, nervous, system, during, development])]). relacion([sujeto(['In', this, 'study,', we]), verbo([report]), complemento([that, forced, expression, of, 'GATA-3', resulted, in, an, increased, number, of, dopamine, 'beta-hydroxylase', '(', 'DBH)-expressing', neurons, in, primary, neural, crest, stem, cell, '(', 'NCSC)', 'culture,', suggesting, that, the, 'DBH', gene, may, be, a, downstream, target, gene, of, 'GATA-3'])]). relacion([sujeto(['Surprisingly,', none, of, these, domains, contain, 'GATA-3']), verbo([binding]), complemento([sites, but, encompass, binding, motifs, for, transcription, factors, 'Sp1', and, 'AP4,', respectively])]). relacion([sujeto(['In', the, other, daughter, cell, of, each, 'case,', it, is, proposed, that, chromosome, stabilization, was, achieved, '(', after, 'replication)', by, sister, chromatid, reunion, to, form, a, 'dicentric,', which, broke, at, a, subsequent, 'anaphase,', to, form, an, inverted, duplication, '(', with]), verbo([loss]), complemento([of, the, reciprocal, 'product,', and, the, other, daughter, cell, 'line)'])]). relacion([sujeto(['The', transcription, factor, 'GATA-3', was, shown, to, play, an, important, role, in, 'TH2', cell, 'activation,', but, also, in, the, regulation, of, other, cell, types]), verbo([involved]), complemento([in, bronchial, asthma, including, mast, 'cells,', 'eosinophils,', and, epithelial, cells])]). relacion([sujeto(['Intranasal', administration, of, gd21]), verbo([prevented]), complemento([airway, inflammation, and, mucus, production, and, inhibited, development, of, airway, hyperresponsiveness, to, methacholine, in, models, of, acute, allergic, airway, inflammation])]). relacion([sujeto(['Further', experiments, indicated, that, pulmonary, surfactant, may, facilitate, the, cellular, uptake, of, gd21, by]), verbo([acting]), complemento([as, an, endogenous, transfectant])]). relacion([sujeto(['We', efficiently, generated, a, subset, of, 'T', cells, called, invariant, natural, killer, 'T', '(', 'iNKT)', cells, from, 'ESCs', derived, from, peripheral, iNKT, cells, using, somatic, cell]), verbo([nuclear]), complemento([transfer, '(', 'ntESCs)'])]). relacion([sujeto(['The', gbGATA3, gene, is]), verbo([transcribed]), complemento([into, multiple, splice, variants, lacking, either, one, or, both, zinc, finger, 'domains,', although, the, sequences, of, both, domains, are, fully, conserved, between, ginbuna, and, other, vertebrates])]). relacion([sujeto(['We']), verbo([found]), complemento([that, alternative, splice, site, and, stop, codon, in, gbGATA3, intron, 3, ',', located, between, exons, that, separately, encode, the, two, zinc, finger, 'domains,', are, conserved, among, 'teleosts,', suggesting, that, teleost, 'GATA3', gene, can, be, translated, into, multiple, isoforms])]). relacion([sujeto(['RT-PCR', analysis, revealed, that, the, gbGATA3, is, strongly]), verbo([expressed]), complemento([in, the, 'brain,', thymus, and, gill, of, unstimulated, fish])]). relacion([sujeto(['Real-time', 'PCR', demonstrated, that, expression, levels, of, 'full-length', gbGATA3, and, the, splice, variants, differed, with, tissue, 'type,', but, full, length, was, always, the, predominantly]), verbo([expressed]), complemento([form])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, 'gbGATA3,', including, its, splice, 'variants,', is, involved, in, teleost, 'T-cell', function])]). relacion([sujeto(['The', mechanisms, by, which, human, dendritic, cells, '(', 'DCs)']), verbo([activate]), complemento([a, 'TH1-polarizing', or, 'TH2-polarizing', program, are, still, partially, unclear])]). relacion([sujeto(['Expression', of, 'Jagged-1', and, 'Delta-4', 'Notch', ligands, and, of, 'GATA-3', and, 'T-box']), verbo([expressed]), complemento([in, 'T', cells, transcription, factors, was, evaluated, by, 'real-time', quantitative, 'PCR'])]). relacion([sujeto(['Myeloid', immature, 'DCs', constitutively]), verbo([expressed]), complemento(['Jagged-1,', which, induces, in, 'CD4+', 'T', cells, a, 'TH2', 'polarization,', as, shown, by, 'Jagged-1', gene, silencing])]). relacion([sujeto(['The', 'TH2', polarization]), verbo([associated]), complemento([with, high, 'GATA-3/T-box', expressed, in, 'T', cells, ratio, and, was, at, least, partially, dependent, on, the, early, induction, of, 'IL-4'])]). relacion([sujeto(['CD4+', 'T-cell', responses, are, usually, characterized, by, a, prevalent, 'TH2', phenotype, unless, 'TLRs', are]), verbo([triggered]), complemento([on, 'DCs', by, microbial, components])]). relacion([sujeto(['The', 'Th2', cytokine, 'IL-4', remained]), verbo([suppressed]), complemento([throughout, the, study, and, was, accompanied, by, reductions, in, the, 'Th2', regulator, 'GATA3'])]). relacion([sujeto(['Chemokine', 'CXCL-2', expression]), verbo([increased]), complemento([progressively, up, to, 35, d, and, preceded, the, appearance, of, inflammatory, infiltrates])]). relacion([sujeto(['These', data]), verbo([suggest]), complemento([that, 'steatosis,', increased, ethanol, 'metabolism,', a, transient, induction, of, the, innate, immune, response, and, suppression, of, 'Th2', responses, were, acute, consequences, of, ethanol, treatment, and, were, followed, by, suppression, of, 'Th1', responses])]). relacion([sujeto(['However,', the, majority, of, 'necrosis,', apoptosis, and, a, late, peak, of, 'TNFalpha', only, occurred, after, 6, -, 7, weeks, of, 'ethanol,', coincided, with, the, appearance, of, inflammatory, infiltrates, and, were]), verbo([associated]), complemento([with, stimulation, of, hepatocyte, proliferation])]). relacion([sujeto(['The', cells, are, 'pluripotent,', with, the, potential, to, become, hair, cells, and, 'neurons,', the, cochlear, cell, types, whose]), verbo([loss]), complemento([causes, deafness])]). relacion([sujeto(['Based', on, marker, 'expression,', retinoic, acid]), verbo([increased]), complemento([the, yield, of, neurons, and, the, percentage, of, sensory, neurons, obtained, and, caused, a, sharp, increase, in, 'Pax2,', a, key, transcription, factor, of, cranial, placodes])]). relacion([sujeto(['Markers', of, embryonic, auditory, and, other, sensory, 'neurons,', 'GATA3,', 'Brn3a,', and, 'islet1,', could, be, detected, after, 3, days, of, differentiation, of, the, 'cells,', and, markers, of, the, sensory, 'phenotype,', 'peripherin,', 'calretinin,', 'TrkC,', and, 'TrkB', were]), verbo([expressed]), complemento([after, 10, days])]). relacion([sujeto(['Development', of, functional, activity, in, cells, with, the, markers, of, sensory, neurons]), verbo([suggested]), complemento([that, the, inner, ear, stem, cells, might, have, the, capacity, to, replace, cells, lost, due, to, neural, degeneration])]). relacion([sujeto(['Pegylated', granulocyte, 'colony-stimulating', factor, '(', 'G-CSF)']), verbo([has]), complemento([recently, been, introduced, as, a, new, compound, for, mobilization, of, 'CD34(+)', hematopoietic, stem, and, progenitor, cells])]). relacion([sujeto(['Flow', cytometry, and, fluorescence]), verbo([activated]), complemento([cell, sorting, was, conducted, to, assess, the, 'CD34(+)', subset, composition, and, to, obtain, 'Lin(-),', 'CD34(+),', 'CD38(-)', hematopoietic, stem, cells])]). relacion([sujeto(['We']), verbo([found]), complemento([lower, expression, of, genes, characteristic, of, erythroid, and, later, stages, of, myeloid, differentiation, and, a, lower, functional, 'burst-forming', unit, 'erythroid/colony-forming', 'unit-granulocyte-macrophage', ratio])]). relacion([sujeto(['Consistently,', greater, numbers, of, hematopoietic, stem, cells, and, common, myeloid, progenitors, and, fewer, 'megakaryocyte-erthrocyte', progenitors, were]), verbo([found]), complemento([in, the, 'pegylated-G-CSF-mobilized', 'CD34(+)', cells])]). relacion([sujeto(['Stimulation', with, 'pegylated-G-CSF', or, 'G-CSF', results, in, different, expression, of, key, regulatory, genes, and, different, functional, properties, of, mobilized, hematopoietic, stem, cells, as, well, as, their, 'progeny,', a]), verbo([finding]), complemento([that, might, be, relevant, for, the, application, of, these, cells, in, blood, stem, cell, transplantation])]). relacion([sujeto(['GATA-3', is, a, transcription, factor]), verbo([involved]), complemento([in, human, growth, and, differentiation])]). relacion([sujeto(['Gene', expression, profiling]), verbo([has]), complemento([shown, that, 'GATA-3', is, highly, expressed, in, the, 'Luminal', 'A', subtype, of, breast, cancer])]). relacion([sujeto(['A', recent, study]), verbo([found]), complemento(['GATA-3', to, be, associated, with, favorable, breast, cancer, pathologic, 'features,', including, negative, lymph, node, and, positive, estrogen, receptor, '(', 'ER)', status])]). relacion([sujeto(['GATA-3', levels, were, also]), verbo([found]), complemento([to, be, an, independent, prognostic, 'marker,', with, low, expression, predicting, for, breast, cancer, recurrence])]). relacion([sujeto(['We', considered, &, 'gt;5%']), verbo([nuclear]), complemento([staining, to, be, a, positive, result, for, 'GATA-3'])]). relacion([sujeto(['GATA-3', is, almost, exclusively]), verbo([expressed]), complemento([in, 'ER+', patients, and, is, also, associated, with, lower, tumor, 'grade,', older, age, at, 'diagnosis,', and, the, absence, of, 'Her2', overexpression])]). relacion([sujeto(['GATA-3', is, a, molecular, marker, that, is, highly]), verbo([associated]), complemento([with, 'ER', 'expression,', but, it, does, not, seem, to, have, prognostic, value, independent, of, 'ER,', nor, does, it, predict, for, response, to, tamoxifen, among, 'ER-positive', patients])]). relacion([sujeto(['The', overexpression, of, 'GATA-3', in, patients, with, allergic, rhinitis, was, related, to, the]), verbo([decrease]), complemento([of, 'IL-12,', and, to, increasing, the, expression, of, 'IL-12', in, topical, tissue, could, suppress, the, expression, of, 'GATA-3', and, may, improve, the, therapeutic, effectiveness, of, 'AR'])]). relacion([sujeto(['The', etiology]), verbo([has]), complemento([not, been, clarified, 'yet,', but, immune, disorder, is, thought, to, be, involved, in, the, pathogenic, physiology])]). relacion([sujeto(['Recently,', general, consensus]), verbo([has]), complemento([been, reached, that, 'CD', and, 'UC', are, 'distinct,', especially, in, respect, of, the, immune, response])]). relacion([sujeto(['Interestingly,', smoking]), verbo([has]), complemento([diverse, effects, on, 'CD,', 'Th1-type', 'enteritis,', and, on, 'UC,', 'Th2-type'])]). relacion([sujeto(['In', this, 'study,', we, first, demonstrated, by, 'RT-PCR', analysis, that, human, lamina, propria, 'T', '(', 'LPT)', cells, had, nicotinic, acetylcholine, receptor, '(', 'nAChR),', and]), verbo([express]), complemento([alpha7, nAChR, subunit, universally])]). relacion([sujeto(['The', effect, of, nicotine, was]), verbo([inhibited]), complemento([by, mecamylamine, '(', 'MEC)'])]). relacion([sujeto(['These', results]), verbo([suggested]), complemento([that, nicotine, could, modulate, the, immune, balance, to, 'Th1-dominant', via, nAChR, in, the, 'intestine,', to, improve, 'Th2-type', enteritis])]). relacion([sujeto(['This', may]), verbo([provide]), complemento([the, experimental, evidence, for, the, fact, that, nicotine, has, a, beneficial, influence, on, 'UC,', and, exacerbates, 'CD'])]). relacion([sujeto(['Furthermore,', it, is, of, great, interest, that, nicotine]), verbo([acts]), complemento([oppositely, on, 'CD', and, 'UC', by, modulation, of, the, mucosal, immune, balance, via, the, neurotransmitter, receptor])]). relacion([sujeto(['Bioinformatic', analysis, revealed, that]), verbo([loss]), complemento([of, the, transcription, factor, 'GATA-3', marked, progression, from, adenoma, to, early, carcinoma, and, onset, of, tumor, dissemination])]). relacion([sujeto(['Restoration', of, 'GATA-3', in, late, carcinomas]), verbo([induced]), complemento([tumor, differentiation, and, suppressed, tumor, dissemination])]). relacion([sujeto(['Targeted', deletion, of, 'GATA-3', in, early, tumors]), verbo([led]), complemento([to, apoptosis, of, differentiated, 'cells,', indicating, that, its, loss, is, not, sufficient, for, malignant, conversion])]). relacion([sujeto(['These', data, indicate, that, 'GATA-3']), verbo([regulates]), complemento([tumor, differentiation, and, suppresses, tumor, dissemination, in, breast, cancer])]). relacion([sujeto(['It']), verbo([has]), complemento([been, suggested, that, 'T-cell', 'immunoglobulin-and', 'mucin-domain-containing', 'molecule-1', '(', 'TIM-1)', plays, an, important, role, in, the, development, of, allergic, 'asthma,', though, its, molecular, mechanism, remains, unclear])]). relacion([sujeto(['These', results, demonstrate, that, 'TIM-1', was, significantly]), verbo([increased]), complemento([in, pulmonary, tissues, and, 'PBMCs', in, asthmatic, mice, after, ovalbumin, '(', 'OVA)', challenge, '(', 'P<0'])]). relacion([sujeto(['The', results, of, this, study]), verbo([provide]), complemento([the, first, evidence, that, increased, expression, of, 'TIM-1', in, asthmatic, mice, is, associated, with, the, 'Th2-associated', transcription, factor, 'GATA-3'])]). relacion([sujeto(['The', findings]), verbo([suggest]), complemento([a, possible, mechanism, for, how, 'HAV', infection, and, 'TIM-1', upregulation, influence, the, development, of, allergic, asthma])]). relacion([sujeto(['Low', level, of, its, gene, expression, and, corresponding, ineffective, protection, of, fetus, from, toxic, compounds, is]), verbo([associated]), complemento([with, pregnancy, disorders, such, as, preeclampsia, and, abnormalities, of, fetus, development])]). relacion([sujeto(['It', was, previously]), verbo([reported]), complemento([that, environmental, radioactive, contamination, caused, 'down-regulation', of, 'GSTP1', transcription, in, human, 'placenta,', but, mechanisms, responsible, for, such, changes, were, unclear])]). relacion([sujeto(['In', the, present, study, we]), verbo([have]), complemento([found, that, observed, changes, in, transcription, of, this, gene, are, not, caused, by, promoter, methylation, because, 'GSTP1', promoter, was, not, methylated, in, any, of, analyzed, 91, placental, samples])]). relacion([sujeto(['Using', &, 'quot;Gene', 'Expression', 'Atlas"', online, software, the, placental, expression, profile, of, transcription, factors, known, to]), verbo([interact]), complemento([with, 'GSTP1', promoter, in, other, cell, 'types,', was, identified])]). relacion([sujeto(['According', to, computer, analysis, the, genes, coding, for, 'GATA2,', 'GATA3,', 'Fos-B,', 'Nrf3', and, 'MafK', transcription, factors, are, highly]), verbo([expressed]), complemento([in, human, 'placenta,', while, genes, coding, for, 'c-Fos,', 'Juns,', 'Mafs,', 'ERbeta,', 'RARalpha', and, 'NF-kappaB', factors, have, moderate, level, of, expression])]). relacion([sujeto(['Competitive', 'EMSA']), verbo([provided]), complemento([the, evidence, that, 'ARE', and, 'NF-kappaB-like', sites, specifically, interacted, with, placental, nuclear, proteins])]). relacion([sujeto(['RBP1,', 'TFRC,', 'SPP1,', 'SAA1,', 'ARHGAP8,', and, 'NDRG1,', which, were, 'upregulated,', and, 'GATA3,', 'PLAGL1,', 'APOD,', 'DUSP1,', and, 'CYR61,', which, were, 'downregulated,', were, considered, as, candidate, genes]), verbo([associated]), complemento([with, invasion, of, cervical, cancer])]). relacion([sujeto(['T-Bet', and, 'GATA-3']), verbo([regulate]), complemento([cytokine, expression, in, 'T-lymphocytes'])]). relacion([sujeto(['Previous', work]), verbo([has]), complemento([demonstrated, expression, of, 'T-Bet', in, human, endometrium])]). relacion([sujeto(['T-Bet', and, 'GATA-3', mRNA, were]), verbo([increased]), complemento([in, the, late, secretory, phase])]). relacion([sujeto(['Progesterone', receptor, '(', 'PR)', mRNA, was]), verbo([increased]), complemento([during, the, proliferative, and, early, secretory, phases])]). relacion([sujeto(['PR', protein, displayed]), verbo([nuclear]), complemento([localization, and, maximal, immunostaining, during, the, early, secretory, phase])]). relacion([sujeto(['T-Bet', and, 'GATA-3', are]), verbo([expressed]), complemento([in, endometrial, epithelium, cyclically, during, the, menstrual, cycle])]). relacion([sujeto(['The', expression, patterns, of, 'T-Bet', and, 'GATA-3', oppose, 'PR,']), verbo([suggesting]), complemento([antagonistic, function, 'and/or', regulation, between, 'PR', and, 'T-Bet/GATA-3'])]). relacion([sujeto(['Inactivation', of, serotonin, transporter, '(', 'HTT)', by, pharmacologically, in, the, neonate, or, genetically]), verbo([increases]), complemento([risk, for, depression, in, 'adulthood,', whereas, pharmacological, inhibition, of, 'HTT', ameliorates, symptoms, in, depressed, patients])]). relacion([sujeto(['The', differing, role, of, 'HTT', function, during, early, development, and, in, adult, brain, plasticity, in]), verbo([causing]), complemento([or, reversing, depression, remains, an, unexplained, paradox])]). relacion([sujeto(['Consistent', results, of, the, upstream, regulatory, element, search, and, the, 'co-localization', search, of, these, genes, indicated, that, the, regulation, may, be]), verbo([executed]), complemento([by, 'Pax5,', 'Pax7', and, 'Gata3,', known, to, be, involved, in, the, 'survival,', 'proliferation,', and, migration, of, serotonergic, neurons, in, the, developing, 'brain,', and, these, factors, are, supposed, to, keep, functioning, to, regulate, downstream, genes, related, to, serotonin, system, in, the, adult, brain])]). relacion([sujeto(['In', response, to, 'anemia,', erythropoietin, '(', 'Epo)', gene, transcription, is, markedly]), verbo([induced]), complemento([in, the, kidney, and, liver])]). relacion([sujeto(['To', elucidate, how, 'Epo', gene, expression, is]), verbo([regulated]), complemento([in, 'vivo,', we, established, transgenic, mouse, lines, expressing, green, fluorescent, protein, '(', 'GFP)', under, the, control, of, a, 180, -, kb, mouse, 'Epo', gene, locus])]). relacion([sujeto(['GFP', expression, was]), verbo([induced]), complemento([by, anemia, or, hypoxia, specifically, in, peritubular, interstitial, cells, of, the, kidney, and, hepatocytes, surrounding, the, central, vein])]). relacion([sujeto(['Surprisingly,', renal, 'Epo-producing', cells, had, a, neuronlike, morphology, and]), verbo([expressed]), complemento([neuronal, marker, genes])]). relacion([sujeto(['Since', both, 'GATA-2', and, 'GATA-3']), verbo([bind]), complemento([to, the, 'GATA', box, in, distal, tubular, 'cells,', both, factors, are, likely, to, repress, constitutively, ectopic, 'Epo', gene, expression, in, these, cells])]). relacion([sujeto(['Allergic', asthma, is, an, airway, inflammatory, disease, characterized, by, chronically]), verbo([increased]), complemento([expression, of, multiple, inflammatory, 'proteins,', including, 'cytokines,', 'chemokines,', adhesion, 'molecules,', 'enzymes,', and, receptors])]). relacion([sujeto(['Several', transcription, factors, are, known, to, play, a, crucial, role, in, the, pathogenesis, of, chronic, inflammatory, diseases, such, as, 'asthma,', including, signal, transducer, and, activator, of, transcription, 'factors,']), verbo([nuclear]), complemento(['factor-kappaB,', nuclear, factor, of, activated, 'T', 'cells,', activator, 'protein-1', family, 'proteins,', and, 'Th2', cellrelated, transcription, factors, including, 'GATA3,', 'JunB,', and, 'c-Maf'])]). relacion([sujeto(['Modulation', of, the, activity, of, certain, transcription, factors]), verbo([has]), complemento([been, shown, to, result, in, the, inhibition, of, inflammation, during, asthma])]). relacion([sujeto(['The', results, showed, that, an]), verbo([increase]), complemento([of, 'Th2', cytokine, and, an, inhibition, of, 'Th1', cytokine, were, accompanied, by, an, increased, expression, of, 'GATA-3', protein, and, a, decreased, expression, of, 'T-bet', protein, in, rat, asthmatic, airways, compared, to, those, in, normal, control, group])]). relacion([sujeto(['Intraperitoneal', ligustrazine, administration, could, significantly, lower, the, level, of, 'IL-4', in, 'BALF', and, the, expression, of, 'GATA-3', protein, in, lung, and, also]), verbo([increase]), complemento([the, level, of, 'IFN-gamma', and, 'T-bet', in, asthmatic, 'rats,', resulting, in, a, decreased, percentage, of, eosinophils, '(', 'EOS)', in, 'BALF', and, ameliorated, airway, inflammatory, cell, infiltration])]). relacion([sujeto(['In', 'conclusion,', ligustrazine]), verbo([inhibits]), complemento(['OVA', induced, airway, inflammation, by, modulating, key, master, switches, 'GATA-3', and, 'T-bet', that, result, in, reversing, the, 'Th2', cytokine, patterns, in, asthma])]). relacion([sujeto(['However,', whether, distinct, biochemical, 'features,', unique, to, 'GATA-3', compared, with, other, 'GATA', family, 'members,', are]), verbo([required]), complemento([to, drive, 'T', cell, transcriptional, programs, or, whether, the, 'T', 'cell-specific', functions, of, 'GATA-3', can, simply, be, ascribed, to, its, expression, pattern, is, unclear])]). relacion([sujeto(['In', this, 'study,', we]), verbo([report]), complemento([that, a, heterologous, 'GATA', 'factor,', 'GATA-4,', was, competent, in, supporting, the, development, of, 'CD4+', 'T', cells, but, could, not, fully, compensate, for, 'GATA-3', in, regulating, the, expression, of, 'Th', cytokines])]). relacion([sujeto(['Specifically,', 'GATA-3', was, more, potent, than, 'GATA-4', in, driving, the, production, of, 'IL-13', due, to, a, mechanism, independent, of, 'DNA']), verbo([binding]), complemento([or, chromatin, remodeling, of, the, 'IL-13', locus])]). relacion([sujeto(['The', difference, was, mapped, to, a, partially]), verbo([conserved]), complemento([region, 'C-terminal', to, the, second, zinc, finger])]). relacion([sujeto(['Converting', a, single, proline, residue, located, in, this, region, of, 'GATA-4', to, its, 'counterpart,', a, methionine, of, 'GATA-3,', was, sufficient, to]), verbo([enhance]), complemento([the, 'IL-13-promoting', function, of, 'GATA-4', but, had, no, effect, on, other, cytokines])]). relacion([sujeto(['Taken', 'together,', our, data, demonstrate, that, the, unique, function, of, 'GATA-3', is]), verbo([conferred]), complemento([by, both, its, cell, 'type-specific', expression, and, distinct, protein, structure])]). relacion([sujeto(['This', lower, susceptibility, is, not]), verbo([associated]), complemento([to, classic, 'malaria-resistance', 'genes,', and, the, analysis, of, the, immune, response, to, 'P'])]). relacion([sujeto(['In', the, present, study, we, compared, the, expression, profile, of, a, panel, of, genes]), verbo([involved]), complemento([in, immune, response, in, peripheral, blood, mononuclear, cells, '(', 'PBMC)', from, 'Fulani', and, sympatric, 'Mossi', from, 'Burkina', 'Faso'])]). relacion([sujeto(['An']), verbo([increased]), complemento([expression, of, 'T', helper, 1, '(', 'TH1)-related', genes, '(', 'IL-18,', 'IFNgamma,', and, 'TBX21)', and, 'TH2-related', genes, '(', 'IL-4', and, 'GATA3)', and, a, reduced, expression, of, genes, distinctive, of, 'T', regulatory, activity, '(', 'CTLA4', and, 'FOXP3)', were, observed, in, 'Fulani'])]). relacion([sujeto(['Microarray', analysis, on, 'RNA', from, 'CD4+', 'CD25+', '(', 'T', 'regulatory)', 'cells,', performed, with, a, panel, of, cDNA, probes, specific, for, 96, genes]), verbo([involved]), complemento([in, immune, 'modulation,', indicated, obvious, differences, between, the, two, ethnic, groups, with, 23, '%', of, 'genes,', including, 'TGFbeta,', 'TGFbetaRs,', 'CTLA4,', and, 'FOXP3,', less, expressed, in, 'Fulani', compared, with, 'Mossi', and, 'European', donors, not, exposed, to, malaria])]). relacion([sujeto(['The', results]), verbo([suggest]), complemento([that, the, higher, resistance, to, malaria, of, the, 'Fulani', could, derive, from, a, functional, deficit, of, 'T', regulatory, cells])]). relacion([sujeto(['Previous', studies]), verbo([have]), complemento([suggested, that, 'GATA-3', may, be, involved, in, the, chromatin, remodeling, in, the, 'Th2', cytokine, locus])]). relacion([sujeto(['To', determine, whether, 'GATA-3', exerts, its, effect, on, its]), verbo([target]), complemento([sites, in, the, extrachromosomal, 'status,', cell, transfection, assay, was, performed])]). relacion([sujeto(['In', this, 'assay,', 800, bp, 'IL4', 'promoter-luciferase', constructs, linked, with, 'GATA-3']), verbo([target]), complemento([sites, were, transfected, into, the, 'M12', 'B', cell, 'line,', 'D10', mouse, 'Th2', cell, 'lines,', and, human, 'T', lymphoma, 'Jurkat', cell, lines, with, or, without, the, 'GATA-3', expression, vector])]). relacion([sujeto(['The', 'GATA-3', effects, on, it]), verbo([target]), complemento([sites, were, minimal, in, the, extrachromosomal, 'status,', supporting, the, previous, propositions, that, 'GATA-3', functions, at, the, chromatin, level, by, remodeling, chromatin, structure])]). relacion([sujeto(['Suppressors', of, cytokine, signalling, '(', 'SOCS)', family, members]), verbo([have]), complemento([been, shown, to, play, an, important, role, in, the, balance, of, cytokines, that, determine, the, onset, of, 'T-helper', type, 1, '(', 'Th1)-', and, 'Th2-mediated', immune, responses])]). relacion([sujeto(['In', 'particular,', for, 'cytokine-induced', 'Src-homology', 2, protein, '(', 'CIS),', 'SOCS1,', 'SOCS3', and, 'SOCS5,', a, role, in, the, regulation, of, 'T', cell, differentiation]), verbo([has]), complemento([been, discussed])]). relacion([sujeto(['In', 'addition,', total, and, specific, 'IgE', concentrations]), verbo([have]), complemento([been, measured, by, the, 'Pharmacia', 'CAP', 'System'])]). relacion([sujeto(['In', 'addition,', an, 'up-regulated', 'SOCS1', expression, correlated, with, 'down-regulated', 'T-box']), verbo([expressed]), complemento([in, 'T', cells, '(', 'Tbet)', and, higher, expression, levels, of, 'GATA-binding', protein, 3, '(', 'GATA-3)', and, 'IL-4'])]). relacion([sujeto(['Our', data]), verbo([suggest]), complemento([that, 'SOCS3,', 'SOCS5', and, 'CIS,', which, correlate, with, an, 'up-regulated', 'Th1', and, regulatory, 'T', cell, 'activity,', are, without, relevance, for, the, allergic, status])]). relacion([sujeto(['In', 'contrast,', 'SOCS1', might, be]), verbo([involved]), complemento([in, the, development, of, a, 'Th2-skewed', immune, response, and, subsequent, allergic, sensitizations])]). relacion([sujeto(['Transcription', factors]), verbo([act]), complemento([in, concert, to, induce, lineage, commitment, towards, 'Th1,', 'Th2,', or, 'T', regulatory, '(', 'Treg)', 'cells,', and, their, 'counter-regulatory', mechanisms, were, shown, to, be, critical, for, polarization, between, 'Th1', and, 'Th2', phenotypes])]). relacion([sujeto(['FOXP3', is, an, essential, transcription, factor, for, 'natural,', 'thymus-derived', '(', 'nTreg)', and, inducible, 'Treg', '(', 'iTreg)', 'commitment;', 'however,', the, mechanisms]), verbo([regulating]), complemento([its, expression, are, as, yet, unknown])]). relacion([sujeto(['We', demonstrated, that, interleukin, 4, '(', 'IL-4)', present, at, the, time, of, 'T', cell, priming]), verbo([inhibits]), complemento(['FOXP3'])]). relacion([sujeto(['This', inhibition, is]), verbo([mediated]), complemento([by, direct, binding, of, 'GATA3', to, the, 'FOXP3', 'promoter,', which, represses, its, transactivation, process])]). relacion([sujeto(['Therefore,', this, study]), verbo([provides]), complemento([a, new, understanding, of, tolerance, 'development,', controlled, by, a, type, 2, immune, response])]). relacion([sujeto(['IL-4', treatment, in, mice, reduces, iTreg, cell, 'frequency,', highlighting, that, therapeutic, approaches, that]), verbo([target]), complemento(['IL-4', or, 'GATA3', might, provide, new, preventive, strategies, facilitating, tolerance, induction, particularly, in, 'Th2-mediated', 'diseases,', such, as, allergy])]). relacion([sujeto(['Previously,', we]), verbo([have]), complemento([demonstrated, that, immature, human, dendritic, cells, '(', 'DC)', from, blood, donors, with, allergies, show, rapid, phosphorylation, of, the, 'Th2-associated', signal, transducer, and, activator, of, transcription, 6, '(', 'STAT6)', upon, contact, with, protein, allergens])]). relacion([sujeto(['In', the, present, study, we, investigated, whether, this, process, is]), verbo([regulated]), complemento([by, the, downstream, molecules, suppressor, of, cytokine, signalling, '(', 'SOCS)', 'and/or', by, the, factors, 'T-bet', and, 'GATA3'])]). relacion([sujeto(['Exposure', of, 'DC', to, protein, allergens]), verbo([led]), complemento([to, the, 'up-regulation', of, the, 'Th2-associated', genes, 'SOCS3', and, 'GATA3,', whereas, the, contact, allergen, 'MCI/MI', preferentially, enhanced, the, expression, of, the, 'Th1-associated', gene, 'T-bet'])]). relacion([sujeto(['Treatment', of, immature, 'DC', with, the, antigen, tetanus, toxoid]), verbo([increased]), complemento([both, 'Th1-', and, 'Th2-associated', genes])]). relacion([sujeto(['Our', data, indicate, that, polarization, of, type, 1, versus, type, 2, immune, responses, takes, place, already, at, the, level, of, 'antigen-presenting', 'cells,']), verbo([involving]), complemento([molecules, similar, to, those, used, in, 'T-cell', polarization])]). relacion([sujeto(['Recent', studies]), verbo([have]), complemento([suggested, that, gene, expression, studies, using, urinary, sediment, might, be, a, 'non-invasive', approach, to, assessing, activity, and, pathogenesis, in, glomerulonephritis])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, the, measurement, of, these, target, gene, expressions, might, be, a, 'useful,', 'non-invasive', method, for, clinical, monitoring, and, studying, of, pathogenesis, in, glomerulonephritis])]). relacion([sujeto(['This', study, was, aimed, to, construct, and, select, plasmid, vectors, of, siRNA, which, can, effectively, and, specifically]), verbo([suppress]), complemento([the, gene, expression, of, 'GATA-3'])]). relacion([sujeto(['Plasmid', including, 'PSi338,', 'PSi717', and, 'PSi1232', were, designed, and, constructed, for, 'GATA-3', regarded, as]), verbo([target]), complemento([gene, and, transfected, into, murine, 'P815', cells])]). relacion([sujeto(['The', results, demonstrated, that, the, expressions, of, mRNA, and, protein, of, 'GATA-3', in, 'P815', cells, were]), verbo([inhibited]), complemento([significantly, by, both, of, 'PSi338', and, 'PSi717'])]). relacion([sujeto(['It', is, concluded, that, 'PSi338', and, 'PSi717', siRNA, plasmid, vectors]), verbo([have]), complemento([been, successfully, 'constructed,', and, both, vectors, are, effective, and, specific, siRNA, plasmids, for, suppressing, 'GATA-3', gene, expression])]). relacion([sujeto(['NKX2-5', is, normally]), verbo([expressed]), complemento([in, developing, spleen, and, 'heart,', regulating, fundamental, 'processes,', including, differentiation, and, survival])]). relacion([sujeto(['In', this, study, we, investigated, whether, 'NKX2-5', expression, in, 'T-ALL', cell, lines]), verbo([reactivates]), complemento([these, embryonal, pathways, contributing, to, leukemogenesis])]). relacion([sujeto(['Among', 18, known]), verbo([targets]), complemento(['analyzed,', we, identified, three, genes, regulated, by, 'NKX2-5', in, 'T-ALL', 'cells,', including, myocyte, enhancer, factor, 2, 'C', '(', 'MEF2C)'])]). relacion([sujeto(['Fusion', constructs, with, green, fluorescent, protein, permitted, subcellular, detection, of, 'MEF2C', protein, in]), verbo([nuclear]), complemento([speckles, interpretable, as, repression, complexes])]). relacion([sujeto(['MEF2C', consistently]), verbo([inhibits]), complemento([expression, of, 'NR4A1/NUR77,', which, regulates, apoptosis, via, 'BCL2', transformation])]). relacion([sujeto(['Taken', 'together,', our, data, identify, distinct, mechanisms, underlying, ectopic, 'MEF2C', expression, in, 'T-ALL,', either, as, a, downstream]), verbo([target]), complemento([of, 'NKX2-5,', or, via, chromosomal, aberrations, deleting, proximal, gene, regions])]). relacion([sujeto(['Inflammation', plays, a, key, role, in, the, pathogenesis, of, an, 'AAA', '(', abdominal, aortic, 'aneurysm);', 'however,', the, nature, of, the, inflammatory, factors, and, cellular, 'response(s)']), verbo([involved]), complemento([in, 'AAA', growth, is, controversial])]). relacion([sujeto(['Compared', with, 'ASD,', inflammatory, parameters]), verbo([associated]), complemento([with, 'Th1-type', '[', 'T-bet,', 'IL', '(', 'interleukin)-2,', 'IFN-gamma', '(', 'interferon-gamma),', 'TNF-alpha', '(', tumour, necrosis, 'factor-alpha),', 'IL-1alpha', and, cytotoxic, 'T-cells]', and, 'Th2-type', '[', 'GATA3,', 'IL-4,', 'IL-10,', 'IL-13', and, 'B-cells]', responses, were, all, increased, in, 'AAA', samples])]). relacion([sujeto(['Baseline', p65, 'NF-kappaB', '(']), verbo([nuclear]), complemento([factor, 'kappaB)', and, 'c-Jun', '[', 'AP-1', '(', activator, 'protein-1)]', levels, were, 'comparable,', but, their, activated, forms, were, strongly, increased, in, the, 'AAA', samples])]). relacion([sujeto(['Downstream']), verbo([target]), complemento([genes, of, p65, 'NF-kappaB,', 'c-Jun,', 'IL-6', and, 'IL-8', were, hyperexpressed])]). relacion([sujeto(['Molecular', and, cellular, processes]), verbo([associated]), complemento([with, 'IL-6', and, 'IL-8', hyperactivation, were, enhanced, in, the, 'AAA', 'samples,', i])]). relacion([sujeto(['In', 'conclusion,', our, findings, demonstrate, that, an, 'AAA', is, a, general, inflammatory, condition, which, is, characterized, by]), verbo([enhanced]), complemento([expression, and, activation, of, 'pro-inflammatory', transcription, 'factors,', accompanied, by, 'IL-6', and, 'IL-8', hyperexpression, and, exaggerated, downstream, cellular, 'responses,', which, together, clearly, distinguish, an, 'AAA', from, 'ASD'])]). relacion([sujeto(['However,', the, molecular, interactions, of, 'GATA-3']), verbo([leading]), complemento([to, 'Th2', cytokine, gene, activation, have, not, been, well, characterized])]). relacion([sujeto(['Here,', we]), verbo([reported]), complemento([a, number, of, 'GATA-3', associated, proteins, in, 'Th2', 'cells,', and, one, of, such, proteins, 'Pias1', functioned, as, a, positive, transcriptional, coregulator, for, 'GATA-3'])]). relacion([sujeto(['When', overexpressed, in, 'Th2', 'cells,', 'Pias1']), verbo([enhanced]), complemento([the, expression, of, 'IL-13,', and, to, lesser, 'degrees,', 'IL-4', and, -, 5])]). relacion([sujeto(['In', 'Leishmania', major, 'infection,', manipulating, 'Pias1', expression, in, 'parasite-reactive', 'CD4', 'T', cells, altered, severity, of, disease]), verbo([caused]), complemento([by, 'Th2', responses])]). relacion([sujeto(['In', 'contrast,', 'IL-5', promoter, was, modestly]), verbo([enhanced]), complemento([by, 'Pias1', and, no, effect, was, observed, on, 'IL-4', promoter])]). relacion([sujeto(['GATA3']), verbo([activates]), complemento([transcription, of, the, 'T(H)2', 'cytokines,', including, 'IL13,', an, important, step, in, the, allergic, inflammatory, pathway])]). relacion([sujeto(['We', performed, genetic, association, studies, in, a, cohort, of, children, '(', n, =, 923, ')', who]), verbo([have]), complemento([been, evaluated, for, the, development, of, rhinitis, and, allergic, sensitization, by, means, of, skin, prick, tests, '(', 'SPTs)', at, age, 10, years])]). relacion([sujeto(['Combinations', of, polymorphisms, and, their, interactions]), verbo([increase]), complemento([the, risk, for, rhinitis, and, allergic, sensitization, at, age, 10, years])]). relacion([sujeto([rs1058240, was]), verbo([associated]), complemento([with, rhinitis, and, allergic, rhinitis, '(', 'P', &, 'lt;'])]). relacion([sujeto([5, ')', ',', and, the, 'gene-gene', interaction, 'rs1058240:rs1800925', was]), verbo([associated]), complemento([with, rhinitis, '(', 'P', =])]). relacion([sujeto(['Our', study]), verbo([suggests]), complemento([that, set, associations, of, polymorphisms, are, important, in, studying, genetic, associations, for, complex, 'phenotypes,', such, as, rhinitis, and, atopy])]). relacion([sujeto(['The', 'GATA-binding', family, of, transcription, factors, comprised, of, a, subgroup, of, 'DNA-binding', proteins, that, both]), verbo([bound]), complemento([the, consensus, 'GATA', motif, and, contained, the, class, 'IV', zinc, finger, motif])]). relacion([sujeto(['Phylogeny', analysis, of, 'GATA', factors, isolated, from, vertebrates]), verbo([suggested]), complemento([that, the, six, distinct, vertebrate, 'GATAs', had, descended, from, a, common, ancestral, 'sequence,', and, the, topology, also, suggested, multiple, modes, of, evolution, including, gene, duplication, and, class, 'IV', zinc, finger, motif, recombination])]). relacion([sujeto(['The', activation, and, effector, phenotype, of, 'T', cells, depend, on, the, strength, of, the, interaction, of, the, 'TcR', with, its, cognate, antigen, and, additional, signals]), verbo([provided]), complemento([by, cytokines, and, by, 'co-receptors'])]). relacion([sujeto(['CD43', is, one, of, the, most, abundant, molecules, on, the, surface, of, 'T', 'cells;', it]), verbo([mediates]), complemento([its, own, signalling, events, and, cooperates, with, those, mediated, by, the, 'T', cell, receptor, in, 'T', cell, priming])]). relacion([sujeto(['We']), verbo([have]), complemento([examined, the, role, of, 'CD43', signals, on, the, effector, phenotype, of, adult, 'CD4+', and, 'CD8+', human, 'T', 'cells,', both, alone, and, in, the, presence, of, signals, from, the, 'TcR'])]). relacion([sujeto(['In', freshly, isolated, 'CD4+', 'T', 'cells,', 'CD43', signals, potentiated, expression, of, the, 'IFNgamma', gene]), verbo([induced]), complemento([by, 'TcR', 'activation;', this, was, not, seen, in, 'CD8+', 'T', cells])]). relacion([sujeto(['In', effector, 'cells,', 'CD43', signals, alone]), verbo([induced]), complemento([the, expression, of, the, 'IFNgamma', gene, in, 'CD4+', 'T', cells, and, to, a, lesser, extent, in, 'CD8+', cells])]). relacion([sujeto(['The', combined, signals, from, 'CD43', and, the, 'TcR']), verbo([increased]), complemento([the, transcription, of, the, 'T-bet', gene, in, 'CD4+', 'T', cells, and, inhibited, the, transcription, of, the, 'GATA-3', gene, in, both, populations, of, 'T', 'cells,', thus, predisposing, 'CD4+', 'T', cells, to, commitment, to, the, 'T1', lineage])]). relacion([sujeto(['In', support, of, 'this,', 'CD43', signals]), verbo([induced]), complemento([a, transient, membrane, expression, of, the, 'high-affinity', chains, of, the, receptors, for, 'IL-12', and, 'IFNgamma', in, 'CD4+', 'T', cells])]). relacion([sujeto(['Moreover,', 'CD43', signals]), verbo([induced]), complemento([the, 'co-clustering', of, 'IFNgammaR', and, the, 'TcR', and, cooperated, with, 'TcR', and, 'IL-12', 'signals,', triggering, a, 'co-capping', of, both, receptors, in, 'CD4+', 'populations,', a, phenomenon, that, has, been, associated, with, a, 'T1', commitment])]). relacion([sujeto(['Our', results]), verbo([suggest]), complemento([a, key, role, for, 'CD43', signals, in, the, differentiation, of, human, 'CD4+', 'T', cells, into, a, 'T1', pattern])]). relacion([sujeto(['In', order, to, better, understand, the, locomotor, 'networks,', we]), verbo([have]), complemento([used, different, transgenic, mice, for, anatomical, characterization, of, one, of, these, interneuron, 'groups,', called, 'V2', interneurons])]). relacion([sujeto(['Neurons', in, this, group, are, either, 'V2a', interneurons, marked, by, the, postmitotic, expression, of, the, transcription, factor, 'Chx10,', or, 'V2b', interneurons, which]), verbo([express]), complemento([the, transcription, factors, 'Gata2', and, 'Gata3'])]). relacion([sujeto(['We']), verbo([found]), complemento([that, all, 'V2a', and, most, 'V2b', interneurons, were, ipsilaterally, projecting, in, embryos, as, well, as, in, newborns])]). relacion([sujeto(['Furthermore,', we, demonstrated, that, a, large, proportion, of, 'V2', interneurons]), verbo([expressed]), complemento([the, axon, guidance, molecule, 'EphA4,', a, molecule, previously, shown, to, be, important, for, correct, organization, of, locomotor, networks])]). relacion([sujeto(['GATA-binding', protein, 3, '(', 'GATA3)', is, a, transcription, factor, and, a, putative, tumor, suppressor, that, is, highly]), verbo([expressed]), complemento([in, normal, breast, luminal, epithelium, and, estrogen, receptor, alpha, '(', 'ER)-positive', breast, tumors])]). relacion([sujeto(['Analyses', of, pooled, data]), verbo([suggested]), complemento([a, reduced, risk, of, breast, cancer, associated, with, two, intronic, variants, in, 'GATA3', in, linkage, disequilibrium, '(', rs3802604, in, intron, 3, and, rs570613, in, intron, 4, ')'])]). relacion([sujeto(['Although', no, individual, 'SNPs', were]), verbo([associated]), complemento([with, 'ER-positive', 'tumors,', two, haplotypes, '(', 'GGTC', in, 2, '%', of, controls, and, 'AATT', in, 7, '%', of, 'controls)', showed, significant, and, consistent, associations, with, increased, risk, for, these, tumors, when, compared, with, the, common, haplotype, '(', 'GATT', in, 46, '%', of, 'controls):', 1.71, '(', 1.27, -, 2.32, ')', and, 1.26, '(', 1.03, -, 1.54, ')', ',', respectively])]). relacion([sujeto(['In', 'summary,', data, from, two, independent, study, populations, showed, two, intronic, variants, in, 'GATA3']), verbo([associated]), complemento([with, overall, decreases, in, breast, cancer, risk, and, suggested, heterogeneity, of, these, associations, by, 'ER', status])]). relacion([sujeto(['Hypersensitivity', or, uncontrolled, responses, against, dietary, antigens, can]), verbo([lead]), complemento([to, inflammatory, disorders, like, food, allergy, and, current, models, reflect, a, variety, of, causes, but, do, not, reveal, the, detailed, modulation, of, gut, immunity, in, response, to, food, antigens, after, breakdown, in, mucosal, tolerance])]). relacion([sujeto(['Sensitization', and, challenged, with, peanut, seeds]), verbo([led]), complemento([to, alterations, in, gut, architecture, with, inflammatory, response, characterized, by, oedema, in, lamina, propria, and, cell, infiltrate, composed, mainly, by, 'eosinophils,', mast, 'cells,', 'phagocytes,', natural, killer, and, plasma, 'cells,', together, with, low, percentage, of, 'gammadelta+', and, 'CD4+CD25+Foxp3+', cells, in, 'Peyer\'s', patches])]). relacion([sujeto(['These', animals, also, presented, high, levels, of, specific, 'IgE', and, 'IgG1', in, sera, and, modulation, of, mucosal, immunity, was]), verbo([mediated]), complemento([by, increased, expression, of, 'GATA-3,', 'IL-4,', 'IL-13', and, 'TNF-alpha', in, contrast, to, low, 'IFN-gamma', in, the, gut])]). relacion([sujeto(['In', the, present, 'study,', a, genetic, fusion, molecule, of, 'Bet', v, 1, and, 'CTB', was, produced, to, test, whether, mucosal, application, of, this, construct, would]), verbo([lead]), complemento([to, suppression, of, 'Th2', responses])]). relacion([sujeto(['Intranasal', pretreatment, of, 'BALB/c', mice, with, 'rCTB-Bet', v, 1, prior, to, allergic, sensitisation, with, the, allergen, significantly]), verbo([decreased]), complemento(['IgE', but, markedly, increased, 'allergen-specific', 'IgG2a', levels, in, sera, as, well, as, 'IFN-gamma', production, of, splenocytes])]). relacion([sujeto(['This', 'Th1', shift, was, supported, by, an]), verbo([increased]), complemento(['T-bet/GATA3', mRNA, ratio])]). relacion([sujeto(['IL-5', production, within, the, airways, was]), verbo([suppressed]), complemento([after, the, pretreatment, with, 'rCTB-Bet', v, 1, ',', while, local, 'allergen-specific', 'IgA', antibodies, were, markedly, enhanced, by, pretreatment, with, the, construct])]). relacion([sujeto(['We', showed, previously, that, 'T', cell, receptor, and, 'CD28', 'co-engagement', 'up-regulate', 'ICOS', expression, in]), verbo([activated]), complemento(['T', cells, via, the, induction, of, 'NFATc2'])]). relacion([sujeto(['Although', 'T-bet']), verbo([acted]), complemento([on, the, icos, 'promoter,', 'GATA-3', operated, via, an, icos, 3, '\'', -, 'un-translated', region, element])]). relacion([sujeto(['Interestingly,', 'NFATc2', was]), verbo([found]), complemento([to, bind, promiscuously, the, icos, promoter, in, developing, 'Th0,', 'Th1,', and, 'Th2', cells, but, became, selectively, associated, with, 'T-bet', at, the, promoter, and, with, 'GATA-3', at, the, 3, '\'', -, untranslated, region, in, fully, differentiated, 'Th1', and, 'Th2', 'cells,', respectively])]). relacion([sujeto(['Collectively,', our, results]), verbo([reveal]), complemento([a, temporally, evolving, circuit, in, which, the, 'non-selectively', expressed, 'NFATc2', cooperates, with, 'Th-restricted', 'T-bet', or, 'GATA-3', to, direct, transcription, of, a, costimulatory, gene, via, distinct, regulatory, elements, in, different, 'Th', cells, undergoing, differentiation])]). relacion([sujeto(['Signal', transducer, and, activator, of, transcription, 1, '(', 'STAT1),', an, intracellular, signal, transducer, and, activator, of, transcription, centrally]), verbo([involved]), complemento([in, many, inflammatory, 'pathways,', was, recently, suggested, to, play, an, important, role, in, allergy, related, immune, responses])]). relacion([sujeto(['Haplotype', tagging, single, nucleotide, polymorphisms, '(', 'SNPs)', previously, described, in, the, 'STAT1', gene, were, genotyped, by, 'matrix-assisted', laser, 'desorption/ionization', 'time-of-flight', mass, spectrometry, technology, in, a, 'cross-sectional', study, population, of, 3099, 'German', children]), verbo([recruited]), complemento([and, phenotyped, by, the, 'International', 'Study', of, 'Asthma', and, 'Allergy', in, 'Childhood,', phase, 'II', '(', 'ISAAC', 'II)'])]). relacion([sujeto(['The', polymorphism, 'C39134A', '(', 'rs3771300),', located, in, a, potentially, cis]), verbo([acting]), complemento([regulatory, element, in, 'STAT1', intron, 24, ',', was, inversely, related, to, atopy, measured, by, skin, prick, 'test,', total, and, specific, serum, 'IgE', levels, while, no, effect, on, atopic, disease, risk, was, observed])]). relacion([sujeto(['Because', of, its, location, in, a, highly]), verbo([conserved]), complemento([noncoding, sequence, near, a, putative, 'GATA3', binding, 'site,', this, polymorphism, represents, an, interesting, target, for, further, studies])]). relacion([sujeto(['They', likely, arise, from, clonal, selection, of, cells, that]), verbo([have]), complemento([accumulated, genomic, lesions, induced, by, 'chemo-', and, radiotherapy, and, may, be, further, promoted, by, the, loss, of, 'DNA', repair, 'and/or', other, pathways, ensuring, the, fidelity, of, replicated, 'DNA'])]). relacion([sujeto(['To', distinguish, genomic, imbalances]), verbo([associated]), complemento([with, the, development, of, acute, myeloid, leukemia, '(', 'AML)', in, 'HL', we, used, an, 'array-based', comparative, genomic, hybridization, '(', 'aCGH)', strategy, on, whole, lymph, node, biopsies, of, 'HL', patient])]). relacion([sujeto(['Genomic', imbalances, '(', amplifications, and, 'deletions)']), verbo([associated]), complemento([with, 'AML', outcome, in, 3, classic, 'HL', 'patients,', at, clinical, diagnosis, they, exhibited, a, discrete, individual, variability])]). relacion([sujeto(['They']), verbo([involved]), complemento(['AFM137XA11,', a, 9, p11])]). relacion([sujeto([2, pericentric, 'region;', 'FGFR1,', the, 'FGF', receptor, most, frequently, translocated, in, 'AML;', 'PPARBP,', a, 'co-activator', of]), verbo([nuclear]), complemento([receptors, 'RARalpha,', 'RXR', and, 'TRbeta1;', 'AFM217YD10,', a, 17, q25, telomeric, 'region;', 'FGR,', an, 'SRC2', kinase, involved, in, cytokine, production, by, 'NK', and, 'CD4+', 'NKT', 'cells;', 'GATA3,', a, 'Th2-specific', transcription, 'factor;', 'TOP1,', involved, in, 'DNA', recombination, and, 'repair;', 'WT1,', a, transcription, factor, involved, in, 'CD8+', 'T', cell, response, against, leukaemic, blasts])]). relacion([sujeto(['Here,', we, studied, whether, epigenetics]), verbo([has]), complemento([a, regulatory, function, in, maintaining, 'pre-established', 'T(H)1-like', and, 'T(H)2-like', immunity, in, human, beings])]). relacion([sujeto(['We', focused, on, delineating, the, role, of, endogenous, histone, deacetylase, '(', 'HDAC)', activity, in]), verbo([regulating]), complemento([cytokine, recall, responses])]). relacion([sujeto(['Using', 'RT-PCR', and, 'ELISA,', the, effect, of]), verbo([increasing]), complemento([cellular, acetylation, on, 'T(H)1/T(H)2', cytokine, expression, was, systematically, examined, in, 58, children, by, inhibiting, 'HDAC', activity, with, trichostatin, 'A'])]). relacion([sujeto(['Phytohemagglutinin', activation, selectively]), verbo([stimulates]), complemento(['antigen-experienced', 'CD45RO+', 'T', 'cells,', eliciting, recall, cytokine, responses])]). relacion([sujeto(['The', resulting, cellular, hyperacetylation]), verbo([led]), complemento([to, increased, 'T(H)2-associated', '(', 'IL-13,', 139, '%', ;, 'IL-5,', 168, '%', ;, 'P', &, 'lt;'])]). relacion([sujeto(['These', alterations, in, 'T(H)2-associated', and, 'T(H)1-associated', recall, responses, were]), verbo([associated]), complemento([with, increased, expression, of, 'Gata-3', and, sphingosine, kinase, 1, ',', a, 'T(H)1-negative', 'regulator,', independent, of, 'T-bet', expression])]). relacion([sujeto(['Endogenous', 'HDAC', activity, plays, a, crucial, role, in]), verbo([maintaining]), complemento([the, balance, of, 'pre-established', 'T(H)1-like', and, 'T(H)2-like', 'responses,', inhibiting, excessive, 'T(H)2', immunity])]). relacion([sujeto(['In', the, imiquimod, 'group,', the, mRNA, and, protein, expressions, of, 'T-bet', '(', 0.48, +, /, -, 0.08, ',', 0.48, +, /, -, 0.17, ')', were, significantly]), verbo([increased]), complemento([compared, with, those, of, the, asthmatic, group, '(', 0.08, +, /, -, 0.12, ',', 0.18, +, /, -, 0.06, ',', 'D', =, 120.96, ',', 177.98, ',', all, 'P', &, 'lt;', 0.01, ')', ',', the, mRNA, and, protein, expressions, of, 'GATA-3', in, the, imiquimod, group, were, both, significantly, decreased, compared, with, those, of, the, asthmatic, group, '(', 'D', =, 166.96, ',', 310.97, ',', all, 'P', &, 'lt;', 0.01, ')'])]). relacion([sujeto(['After', 24, or, 48, h, 'stimulation,', the, concentrations, of, 'IFN-gamma', in, drug, 2, subgroup, '[', '(', 149, +, /, -, 31, ')', ',', '(', 154, +, /, -, 28, ')', 'pg/ml]', and, drug, 3, subgroup, '[', '(', 166, +, /, -, 30, ')', ',', '(', 158, +, /, -, 31, ')', 'pg/ml]', were]), verbo([increased]), complemento(['significantly;', 'Levels', of, 'IL-4', '[', druug, 2, 'subgroup:', '(', 23, +, /, -, 5, ')', ',', '(', 39, +, /, -, 11, ')', 'pg/ml,', drug, 3, 'subgroup:', '(', 43, +, /, -, 13, ')', ',', '(', 56, +, /, -, 12, ')', 'pg/ml]', were, increased, slowly, compared, with, those, in, the, 'OVA', group, '(', drug, 2, subgroup, 24, h, 'IL-4,', 'D', =, 9.9, ;, drug, 3, subgroup, 24, h, 'IL-4,', 'D', =, 8.79, ',', drug, 2, subgroup, 48, h, 'IL-4,', 'D', =, 8.8, ',', drug, 3, subgroup, 48, h, 'IL-4,', 'D', =, 8.1, ',', drug, 2, subgroup, 24, h, 'IFN-gamma,', q, =, 4.8, ',', drug, 3, subgroup, 24, h, 'IFN-gamma,', q, =, 6.4, ',', drug, 2, subgroup, 48, h, 'IFN-gamma,', q, =, 3.95, ',', drug, 3, subgroup, 48, h, 'IFN-gamma,', q, =, 4.31, ',', all, 'P', &, 'lt;', 0.05, ')'])]). relacion([sujeto(['After', imiquimod, 'treatment,', the, mRNA, and, protein, levels, of, 'T-bet', in, imiquimod, group, 'CD(4)(+)', 'T', cells, were]), verbo([increased]), complemento([significantly, compared, with, those, in, 'OVA', 'group,', and, the, mRNA, and, protein, levels, of, 'GATA-3', were, decreased, significantly, in, 'CD(4)(+)', 'T', cells, of, imiquimod, group, compared, with, those, in, 'OVA', group])]). relacion([sujeto(['MDC', and, 'TARC', levels, of, serum, in, imiquimod, group, '[', '(', 84, +, /, -, 13, ')', 'pg/ml,', '(', 163, +, /, -, 35, ')', 'pg/ml]']), verbo([decreased]), complemento([as, compared, with, those, in, asthma, group, '(', 'MDC:', q, =, 9.8, ',', 'TARC:', q, =, 4.5, ',', all, 'P', &, 'lt;', 0.01, ')', and, 'MDC', levels, in, imiquimod, group, were, no, different, with, normal, group, '(', q, =, 1.8, ',', 'P', &, 'gt;', 0.05, ')'])]). relacion([sujeto([eotaxin, levels, of, serum, in, imiquimod, group, '[', '(', 501, +, /, -, 76, ')', 'pg/ml]']), verbo([increased]), complemento([as, compared, with, those, from, normal, group, '(', q, =, 8.5, ',', 'P', &, 'lt;', 0.01, ')', ',', and, decreased, as, compared, with, those, from, asthma, group, '(', q, =, 3.7, ',', 'P', &, 'lt;', 0.05, ')'])]). relacion([sujeto(['(', 4, ')', 'The', expression, of, 'eoaxin,', 'MDC,', 'TARC', and, 'STAT(6)', on, the, bronchial, epithelium, in, imiquimod, group, was]), verbo([decreased]), complemento([as, compared, with, asthma, 'group,', but, increased, as, compared, with, normal, group])]). relacion([sujeto(['These', findings]), verbo([suggested]), complemento([that, imiquimod, can, inhibit, the, airway, inflammation, of, asthma, animals, by, reducing, 'GATA-3', mRNA, and, protein, expression, and, increasing, 'T-bet,', 'STAT(6)', mRNA, and, protein, expression])]). relacion([sujeto(['However,', 'Hyp']), verbo([has]), complemento([been, found, to, possess, several, other, biological, 'properties,', including, inhibitory, effects, on, tumor, 'invasion,', 'angiogenesis,', and, inflammation])]). relacion([sujeto(['In', this, 'paper,', we, show, that, treatment, with, 'Hyp']), verbo([inhibited]), complemento(['IFN-gamma', 'production,', with, 'down-regulation', of, 'T-box', '(', 'T-bet;', marker, of, 'Th1', gene, 'expression)', and, 'up-regulation', of, 'GATA-3', '(', marker, gene, of, 'Th2)', on, 'IL-2/PHA-activated', 'T', cells])]). relacion([sujeto(['In', 'parallel,', we, showed, a, strong, 'down-regulation', of, the, chemokine, receptor, 'CXCR3', expression, on]), verbo([activated]), complemento(['T', cells])]). relacion([sujeto(['The', latter, effect, and, the, 'down-modulation', of, matrix, metalloproteinase, 9, expression, may, eventually]), verbo([lead]), complemento([to, the, inhibition, of, migratory, capability, and, matrix, traversal, toward, the, chemoattractant, 'CXCL10', by, activated, lymphocytes, that, we, observed, in, vitro])]). relacion([sujeto(['A', growing, body, of, literature]), verbo([has]), complemento([examined, and, implicated, 'DNA', methylation, as, a, critical, epigenetic, modification, in, 'T', helper, '(', 'Th)', cell, differentiation])]). relacion([sujeto(['The', absence, of, 'DNA', methyltransferases, or, 'methyl-binding', proteins, derepresses, many, cytokine, 'loci,', allowing, their, ectopic, 'expression,', while, methylation, of, specific, 'CpG', residues, is, sufficient, to]), verbo([prevent]), complemento([expression])]). relacion([sujeto([rad50, hypersensitive, site, 7, '(', 'RHS7),', a, hypersensitive, site, within, this, 'LCR,', becomes, demethylated, in, a, 'STAT6-dependent', manner, and, only, in, cells]), verbo([stimulated]), complemento([under, type, 2, conditions])]). relacion([sujeto(['Robust', demethylation, appears, to]), verbo([require]), complemento([signaling, contributions, from, both, 'IL-4', 'receptor,', via, 'STAT6,', and, 'CD28,', but, it, cannot, be, effected, by, 'GATA3'])]). relacion([sujeto(['Apart', from, known, steroid, 'effects,', calcitriol, in, particular]), verbo([promoted]), complemento([regulatory, 'T', cell, profiles, as, indicated, by, a, marked, increase, of, 'IL-10,', 'TGFbeta,', 'FoxP3,', and, 'CTLA4'])]). relacion([sujeto(['Furthermore', they]), verbo([suggest]), complemento([that, early, markers, of, inflammatory, dendritic, cell, and, 'Th17', differentiation, qualify, as, new, target, molecules, for, both, calcitriol, and, highly, selective, 'immune-modulating', vitamin, 'D', analogs])]). relacion([sujeto(['Chemoattractant-receptor', homologous, molecule]), verbo([expressed]), complemento([on, 'Th2', cells, '(', 'CRTh2)', is, a, receptor, for, prostaglandin, '(', 'PG)D2,', a, lipid, mediator, involved, in, allergic, inflammation])]). relacion([sujeto(['CRTh2', is]), verbo([expressed]), complemento([by, 'Th2', 'cells,', eosinophils, and, basophils, and, 'PDG(2)-CRTh2', signaling, induces, calcium, 'mobilization,', cell, migration, and, expression, of, the, 'Th2', cytokines, 'IL-4,', 'IL-5,', and, 'IL-13'])]). relacion([sujeto(['Despite', the, role, of, 'CRTh2', in, allergic, 'inflammation,', transcriptional, regulation, of, this, gene]), verbo([has]), complemento([not, been, studied])]). relacion([sujeto(['Here,', we, demonstrated, that, a, reporter, construct, of, the, 'CRTh2', promoter, was]), verbo([induced]), complemento([following, 'T', cell, stimulation])]). relacion([sujeto(['This', activity, could, be, further]), verbo([enhanced]), complemento([by, 'over-expression', of, 'GATA-3,', but, not, 'NFAT2', or, 'STAT6'])]). relacion([sujeto(['Electromobility', shift, assay, demonstrated, 'GATA-3']), verbo([binding]), complemento([to, a, probe, from, the, 'CRTh2', promoter])]). relacion([sujeto(['This', study]), verbo([provides]), complemento([the, first, detailed, analysis, of, transcriptional, regulation, of, the, human, 'CRTh2', promoter])]). relacion([sujeto(['Hence', identification, of, genes, and, their, networks, governing, prenatal, development, of, skeletal, muscles, will]), verbo([provide]), complemento([insight, into, the, control, of, muscle, growth, and, facilitate, finding, the, source, of, its, variation])]). relacion([sujeto(['So', far, most, of, the, genes]), verbo([involved]), complemento([in, myogenesis, were, identified, by, in, vitro, studies, using, gene, targeting, and, transgenesis])]). relacion([sujeto(['Out', of, the, resulting, 85, unique]), verbo([expressed]), complemento([sequence, 'tags,', 'EST,', 52, could, be, assigned, to, known, genes])]). relacion([sujeto(['The', most, frequent, functional, categories, represented, genes, encoding, myofibrillar, proteins, '(', 8, ')', ',', genes]), verbo([involved]), complemento([in, cell, 'adhesion,', 'cell-cell', signaling, and, extracellular, matrix, 'synthesis/remodeling', '(', 8, ')', ',', genes, regulating, gene, expression, '(', 8, ')', ',', and, metabolism, genes, '(', 8, ')'])]). relacion([sujeto(['Nine', of, the]), verbo([target]), complemento([transcripts, showed, higher, than, twofold, differences, in, the, expression, between, the, two, breeds, '(', 'GATA3,', 'HMGA2,', 'NRAP,', 'SMC6L1,', 'SPP1,', 'RAB6IP2,', 'TJP1', and, two, 'EST)'])]). relacion([sujeto(['The', present, study, revealed, several, genes, and, novel, transcripts, not, previously]), verbo([associated]), complemento([with, myogenesis, and, expands, our, knowledge, of, genetic, factors, operating, during, myogenesis])]). relacion([sujeto(['It', was]), verbo([found]), complemento([recently, that, the, peripheral, 'NK', cell, pool, consists, largely, of, bone, marrow, '(', 'BM)-derived', and, 'thymus-derived', 'cells,', which, are, phenotypically, and, functionally, different])]). relacion([sujeto(['The', effects, of, alcohol, consumption, on, these, subpopulations]), verbo([have]), complemento([not, been, studied, previously])]). relacion([sujeto(['Using', a, 'well-established', 'alcohol-feeding', 'model,', we]), verbo([found]), complemento([that, chronic, alcohol, consumption, decreases, the, percentage, and, number, of, peripheral, 'NK', 'cells,', especially, those, expressing, a, mature, phenotype])]). relacion([sujeto(['NK', cells, in, the, 'BM', were]), verbo([increased]), complemento(['significantly;', 'however,', proliferation, rate, was, not, altered, by, alcohol, 'consumption,', which, increased, 'CD127+', and, decreased, 'Ly49D+', 'NK', cells, in, the, spleen, but, not, in, the, 'BM'])]). relacion([sujeto(['Chronic', alcohol, consumption]), verbo([increased]), complemento(['IFN-gamma-producing', 'NK', cells, and, 'GATA-3', expression, in, splenic, 'NK', cells])]). relacion([sujeto(['The']), verbo([increased]), complemento([proportion, of, 'thymus-derived', 'NK', cells, in, the, spleen, likely, results, from, impaired, 'NK', cell, release, from, the, 'BM'])]). relacion([sujeto(['Following', antigen, 'challenge,', adoptively, transferred, 'antigen-specific', 'CD4(+)', 'T', cells]), verbo([induce]), complemento([allergic, airway, 'inflammation,', comprised, primarily, of, an, increase, in, lymphocytes, and, eosinophils])]). relacion([sujeto(['Our', goal, was, to, better, understand, the, contribution, of, the, 'GATA-3', transcription, factor, to, the, ability, of, adoptively, transferred, 'T', cells, to]), verbo([induce]), complemento([airway, inflammation, in, the, 'Brown', 'Norway', rat, model, of, adoptively, transferred, asthma])]). relacion([sujeto(['We', transduced, 'antigen-stimulated', 'CD4+', 'T', cells, with, recombinant, retroviruses, encoding]), verbo([enhanced]), complemento([green, fluorescent, protein, '(', 'EGFP)', only, or, 'EGFP', and, the, 'GATA-3', transcription, factor])]). relacion([sujeto(['Our', data, indicate, that, 'T', cells, transduced, with, retroviruses, encoding, 'GATA-3']), verbo([expressed]), complemento([high, levels, of, 'GATA-3', protein, as, well, as, 'T-helper', type, 2, cytokines])]). relacion([sujeto(['Following', adoptive, transfer, and, airway, antigen, 'challenge,', these, 'gene-modified', 'T', cells]), verbo([induced]), complemento([robust, inflammatory, responses, in, the, lungs, and, draining, lymph, nodes])]). relacion([sujeto(['In', 'addition,', the, number, of, antigen, 'non-specific', 'CD4+', 'T', cells, recovered, in, the, 'BALF', as, well, as, the, lung, and, draining, lymph, nodes, was]), verbo([enhanced]), complemento([in, recipients, of, 'GATA-3', overexpressing, 'T', cells, following, antigen, challenge])]). relacion([sujeto(['These', data]), verbo([provide]), complemento([evidence, that, 'GATA-3', plays, a, significant, role, in, the, ability, of, 'antigen-specific', 'T', cells, to, amplify, allergic, inflammatory, responses, in, vivo, by, promoting, the, recruitment, of, endogenous, antigen, 'non-specific', 'T', cells, to, the, lung])]). relacion([sujeto(['GATA-3', is, the, key, transcriptional, factor, for, 'Th2', commitment, in, 'T', cells, and, is, strongly]), verbo([associated]), complemento([with, asthma, and, allergic, disease])]). relacion([sujeto(['While', evaluating, 'AHR', by, means, of]), verbo([enhanced]), complemento([pause, '(', 'Penh)', and, pulmonary, resistance, '(', 'R(L))', using, body, 'plethysmography,', it, was, found, that, the, administration, of, 'Lenti-si-GATA-3', had, significantly, decreased, 'AHR', in, 'OVA-immunized', mice])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, inhibition, of, 'GATA-3', gene, expression, by, shRNAs, lentiviral, vectors, strongly, attenuates, 'antigen-induced', airway, inflammation, and, 'hyper-responsiveness', in, mice])]). relacion([sujeto(['CD4(+)CD25(+)', 'Tregs', are, either, naturally, occurring, or]), verbo([induced]), complemento([by, antigens, and, are, characterized, by, the, expression, of, the, 'X-linked', 'forkhead/winged', helix, transcription, 'factor,', 'Foxp3'])]). relacion([sujeto(['Here', we]), verbo([report]), complemento([a, previously, unrecognized, subset, of, 'CD4(+)CD25(+)', 'Tregs', derived, from, 'CD4(+)CD25(-)', 'T', cells, induced, by, nitric, oxide, '(', 'NO)'])]). relacion([sujeto(['NO-Tregs']), verbo([suppressed]), complemento([the, proliferation, of, 'CD4(+)CD25(-)', 'T', cells, in, vitro, and, attenuated, 'colitis-', and, 'collagen-induced', arthritis, in, vivo, in, an, 'IL-10-dependent', manner])]). relacion([sujeto(['NO-Tregs', also, were]), verbo([induced]), complemento([in, vivo, in, 'SCID', mice, adoptively, transferred, with, 'CD4(+)CD25(-)', 'T', cells, in, the, presence, of, 'LPS', and, 'IFNgamma,', and, the, induction, was, completely, inhibited, by, 'N(G)-monomethyl-L-arginine,', a, pan, 'NO', synthase, inhibitor])]). relacion([sujeto(['Interleukin', '(', 'IL)-5', is, a, key, regulator, of, eosinophilia, in, allergic, inflammation, and, parasite, infections, but, the, mechanisms]), verbo([regulating]), complemento(['IL-5', expression, in, activated, human, 'T', lymphocytes, are, poorly, understood])]). relacion([sujeto(['From', studies, on, mouse, 'cells,', the, activation, protein, '(', 'AP)-1', and, 'GATA-3', sites, in, the, proximal, promoter, region, appear, to, be, important, in, 'IL-5', regulation, but, the, significance, of, an, adjacent, 'Ets/nuclear', factor, of]), verbo([activated]), complemento(['T', cell, '(', 'NFAT)', site, has, been, less, clear])]). relacion([sujeto(['Transcription', factor]), verbo([binding]), complemento([was, shown, with, chromatin, immunoprecipitation, '(', 'ChIP)'])]). relacion([sujeto(['Mutation', of, reporter, gene, plasmids, showed, the, 'Ets/NFAT', site, was, of, equal, importance, to, the, 'AP-1', and, 'GATA-3', sites, in]), verbo([regulating]), complemento(['IL-5', transcription])]). relacion([sujeto(['Transactivation', by, 'Ets1']), verbo([increased]), complemento([luciferase, expression, 15, -, 'fold,', in, the, absence, of, 'stimulation,', and, 'AP-1', '(', 'c-Fos/c-Jun)', and, 'GATA-3', gave, transactivations, of, 85, -, 'fold,', and, 100, -, 'fold,', respectively])]). relacion([sujeto(['Dominant-negative', 'AP-1']), verbo([inhibited]), complemento(['IL-5', transcription])]). relacion([sujeto(['Chromatin', immunoprecipitation, showed]), verbo([increased]), complemento([binding, of, 'Ets1', and, 'GATA-3', to, the, 'IL-5', promoter, after, stimulation])]). relacion([sujeto(['Ets1,', 'GATA-3', and, 'AP-1', synergize, to]), verbo([regulate]), complemento(['IL-5', transcription, in, human, 'T', cells])]). relacion([sujeto(['GATA4', and, 'GATA6']), verbo([have]), complemento([been, demonstrated, to, induce, mouse, embryonic, stem, '(', 'mES)', cells, differentiation, toward, extraembryonic, endoderm, '(', 'ExE)'])]). relacion([sujeto(['We', believe, this]), verbo([finding]), complemento([can, augment, our, understanding, of, mouse, 'ES', cell, differentiation])]). relacion([sujeto(['Hypersensitivity', pneumonitis, '(', 'HP)', is]), verbo([mediated]), complemento([by, a, 'Th1', immune, response])]). relacion([sujeto(['Transcription', factor, 'GATA']), verbo([binding]), complemento(['protein-3', '(', 'GATA-3)', is, believed, to, be, a, key, regulator, of, 'Th2', differentiation, and, thus, might, play, regulatory, roles, in, the, pathogenesis, of, hypersensitivity, pneumonitis, '(', 'HP)'])]). relacion([sujeto(['HP', was]), verbo([induced]), complemento([by, repeated, exposure, to, 'Saccharopolyspora', 'rectivirgula,', the, causative, antigen, of, 'farmer\'s', lung])]). relacion([sujeto(['Antigen', exposure, resulted, in, a, marked, inflammatory, response, with]), verbo([enhanced]), complemento([pulmonary, expression, of, 'T-bet', and, the, 'Th1', cytokine, interferon, '(', 'IFN)-gamma', in, 'wild-type', mice])]). relacion([sujeto(['Supplementation', with, recombinant, 'IFN-gamma']), verbo([enhanced]), complemento([lung, inflammatory, responses, in, 'GATA-3-overexpressing', mice, to, the, level, of, 'wild-type', mice])]). relacion([sujeto(['Totally', 38, asthmatic, 'children,', including, acute, attack, group, composed, of, 20, cases, '(', age, 3, -, 13, 'years,', mean, 6.2, +, /, -, 2.9, ')', ',', remission, group, with, 18, cases, '(', age, 3, -, 12, 'years,', mean, 6.1, +, /, -, 2.5, ')', and, 20, healthy, control, children, '(', age, 3, -, 12, ',', 6.9, +, /, -, 2.7, ')', were]), verbo([recruited]), complemento([in, this, study, from, 'Sep'])]). relacion([sujeto(['Recent', advance, in, mouse, genomics]), verbo([has]), complemento([provided, us, lots, of, information, concerning, genes, playing, critical, roles, during, organogenesis, of, parathyroid, gland])]). relacion([sujeto(['And', human, counterparts, of, murine, hypoparathyroidism, produced, by, gene, manipulation]), verbo([have]), complemento([been, identified])]). relacion([sujeto(['Hypoparathyroidism', is, characterized, by]), verbo([decreased]), complemento([actions, of, parathyroid, hormone, '(', 'PTH)', either, by, reduced, secretion, of, or, resistance, to, 'PTH'])]). relacion([sujeto(['The', understanding, in, the, pathogenesis, of, hypoparathyroidism]), verbo([has]), complemento([been, greatly, increased, by, recent, findings, in, genetic, abnormalities, of, patients, with, hypoparathyroidism])]). relacion([sujeto(['Both', 'Th1', and, 'Th2', differentiation, can, be]), verbo([induced]), complemento([by, 'Notch,', but, what, dictates, which, of, these, programs, is, activated, in, response, to, 'Notch', is, not, known])]). relacion([sujeto(['By', using, 'T', 'cell-specific', gene, ablation, of, the, 'Notch', effector, 'RBP-J', or, the, 'Notch1', and, 2, 'receptors,', we, showed, here, that, 'Notch', was]), verbo([required]), complemento([on, 'CD4(+)', 'T', cells, for, physiological, 'Th2', responses, to, parasite, antigens])]). relacion([sujeto(['GATA-3', was, necessary, for, 'Notch-induced', 'Th2', 'differentiation,', and, we, identified, an, upstream, 'Gata3', promoter, as, a, direct]), verbo([target]), complemento([for, 'Notch', signaling])]). relacion([sujeto(['During', helper, 'T', '(', 'Th)', cell, 'differentiation,', 'Notch', is]), verbo([involved]), complemento([in, generating, optimal, 'Th2', cell, responses])]). relacion([sujeto(['Here,', we, present, data, investigating, how, 'Notch']), verbo([mediates]), complemento(['Th2', cell, differentiation])]). relacion([sujeto(['Notch', showed, a, 'CD4(+)', 'T', cell, intrinsic, role, in]), verbo([promoting]), complemento(['IL-4', expression, that, required, 'GATA-3'])]). relacion([sujeto(['Introduction', of, an]), verbo([activated]), complemento([allele, of, 'Notch1', into, 'CD4(+)', 'T', cells, led, to, the, specific, and, direct, upregulation, of, a, developmentally, regulated, 'Gata3', transcript, that, included, the, exon, 1, a, sequences])]). relacion([sujeto(['Furthermore,', 'Notch']), verbo([acted]), complemento([in, parallel, with, 'GATA-3', to, synergistically, activate, 'IL-4', expression])]). relacion([sujeto(['Together,', these, data, implicate, 'Gata3', as, a, direct, transcriptional, 'Notch']), verbo([target]), complemento([that, acts, in, concert, with, 'Notch', signaling, to, generate, optimal, 'Th2', cell, responses])]). relacion([sujeto(['The', dominant, expression, of, 'GATA-3', gene, was]), verbo([found]), complemento([in, the, 'BMSCs', from, cAA, and, normal, controls])]). relacion([sujeto(['GATA', genes, can, be]), verbo([expressed]), complemento([in, the, 'BMSCs', and, may, play, a, role, in, the, regulation, of, hematopoiesis, in, normal, 'individuals,', as, well, as, in, patients, with, cAA])]). relacion([sujeto(['Risk', of, allergic, diseases]), verbo([has]), complemento([been, linked, to, abnormal, patterns, of, fetal, immune, 'development,', suggesting, that, priming, of, the, immune, system, may, occur, in, utero])]). relacion([sujeto(['CBMC', were]), verbo([stimulated]), complemento([with, 'beta-lactoglobulin,', and, phytohemaglutinin, '(', 'PHA)'])]). relacion([sujeto(['In', 'CBMC-enhanced', induction, of, 'GATA-3,', which]), verbo([activates]), complemento([several, 'Th2', cytokines, 'genes,', was, a, risk, factor, for, 'IgE', sensitization])]). relacion([sujeto(['The', immune, deviation, towards, 'Th2-type', immunity, developed, already, in, utero, and, seemed, to]), verbo([modulate]), complemento([the, pattern, of, immune, response, favoring, an, 'IgE', response, to, environmental, antigens])]). relacion([sujeto(['To', observe, the, effect, of, moxibustion, on, 'Janus', 'kinase-signal', transducer, and, activator, of, transcription, '(', 'JAK-STAT)', pathway, of, synovial, cells, in, rheumatoid, arthritis, '(', 'RA)', rabbits, for]), verbo([revealed]), complemento([the, underlying, mechanism, of, moxibustion, in, the, treatment, of, 'RA'])]). relacion([sujeto(['The', synovial, tissue, of, joint, was, sampled, for, analyzing, the, expression, of, signal, molecules]), verbo([associated]), complemento([with, 'JAK-STAT', pathway, with, gene, chip, and, bioinformation, analytical, techniques])]). relacion([sujeto(['Compared', with, normal, control, 'group,', the, perimeters, of, both, knee, joints, in, model, group]), verbo([increased]), complemento([significantly, from, the, 3, rd, day, to, 21, st, day, after, injection, of, 'FCA', '(', 'P', &, 'lt;', 0.01, ')', ',', while, compared, with, model, 'group,', those, in, moxibustion, group, decreased, considerably, from, the, 6, th, day, on, '(', 'P', &, 'lt;', 0.05, ',', 0.01, ')'])]). relacion([sujeto(['In', comparison, with, control, 'group,', 'JAK-STAT', 'pathway-associated', genes, with, 'up-regulated', expression, in, model, group, were, 'C/EBP', 'beta,', 'CBP,', 'CRP,', 'GATA3,', 'IFNAR1,', 'IFNAR2,', 'IFNGR2,', 'IL-10Rb,', 'INDO,', 'SH2B,', 'STAT3,', 'STAT6,', 'JAK3', and, 'GP130,', and, those, with, 'down-regulated', expression, were, 'A2M,', 'MIG', and, 'IL-2Rr,']), verbo([suggesting]), complemento([an, abnormal, activation, of, 'JAK-STAT', 'pathway;', while, in, comparison, with, model, 'group,', the, related, gene, 'up-regulated', in, moxibustion, group, in, the, expression, was, 'IL22R', and, those, 'down-regulated', were, 'Cyclin', 'D1,', 'C/EBP', 'beta,', 'CRP,', 'GATA3,', 'IFNAR2,', 'INDO,', 'JAK2,', 'JAK3,', 'V-JUN,', 'STAT3,', 'STAT5,', 'SH2B', and, 'OSM,', showing, that, moxibustion, had, an, apparent, inhibitory, effect, on, 'AR-induced', abnormal, activation, of, some, genes, as, 'C/EBP', 'beta,', 'GATA3,', 'IFNAR2,', 'INDO,', etc])]). relacion([sujeto(['Moxibustion', can, resist, inflammation, and, eliminate, swelling, in, 'RA', 'rabbits,', which, may, be, closely, with, its, effect, in]), verbo([inhibiting]), complemento([abnormal, activation, of, 'JAK-STAT', pathway, in, synovial, cells])]). relacion([sujeto(['In', this, 'work,', we]), verbo([have]), complemento([explored, the, suitability, of, the, developing, fetal, cochlea, to, be, used, as, a, source, for, the, extraction, of, auditory, 'progenitor/stem', cells])]). relacion([sujeto(['We']), verbo([have]), complemento([established, cultures, that, express, critical, markers, such, as, 'NESTIN,', 'SOX2,', 'GATA3', and, 'PAX2'])]). relacion([sujeto(['These', cultures, can, be, expanded, in, vitro, for, several, months, and, differentiating, markers, such, as, 'ATOH1/HATH1', and, 'POU4F3/BRN3C', can, be]), verbo([induced]), complemento([by, manipulating, the, culture, conditions, using, specific, growth, factors, such, as, 'bFGF,', 'EGF', and, retinoic, acid])]). relacion([sujeto(['Here,', we, show, that, the, 'c-Myb', transcription, factor, is, a, critical, downstream, regulator, of, positive, 'selection,']), verbo([promoting]), complemento([the, development, of, helper, 'T', cells, and, blocking, the, development, of, cytotoxic, 'T', cells])]). relacion([sujeto(['A', 'gain-of-function', 'c-Myb', transgene, stops, development, of, cytotoxic, 'T', 'cells,', instead]), verbo([causing]), complemento([accumulation, of, a, precursor, population])]). relacion([sujeto(['Conversely,']), verbo([loss]), complemento([of, 'c-Myb', in, selecting, cells, results, in, significantly, fewer, helper, 'T', cells])]). relacion([sujeto(['We', show, that, 'Gata3', is, a, direct]), verbo([target]), complemento([of, 'c-Myb,', and, propose, that, 'c-Myb', is, an, important, regulator, of, 'Gata3,', required, for, transduction, of, the, 'T-cell', receptor, signal, for, subsequent, helper, cell, lineage, differentiation])]). relacion([sujeto(['A', critical, role, for, eosinophils, in, remodeling, of, allergic, airways, was, observed, in, vivo, upon, disruption, of, the, dblGATA, enhancer, that]), verbo([regulates]), complemento([expression, of, 'GATA-1,', which, resulted, in, an, 'eosinophil-deficient', phenotype, in, the, 'DeltadblGATA', mouse])]). relacion([sujeto(['Cultured', 'DeltadblGATA', eosinophils, contain, cytoplasmic, granules, with, immunoreactive, major, basic, protein, and, they]), verbo([express]), complemento([surface, 'Siglec', 'F', and, transcripts, encoding, major, basic, 'protein,', eosinophil, 'peroxidase,', and, 'GATA-1,', -, 2, ',', and, -, 3, to, an, extent, indistinguishable, from, cultured, 'wild-type', eosinophils])]). relacion([sujeto(['Interestingly,', and, in, contrast, to, those, from, the, wild, 'type,', a, majority, of, the, 'GATA-1', transcripts, from, cultured, 'DeltadblGATA', progenitors]), verbo([express]), complemento([a, variant, 'GATA-1', transcript, that, includes, a, first, exon, '(', '1E(B)),', located, approximately, 3700, bp, downstream, to, the, previously, described, first, exon, found, in, hemopoietic, cells, '(', '1E(A))', and, approximately, 42, bp, upstream, to, another, variant, first, 'exon,', '1E(C)'])]). relacion([sujeto(['These', data]), verbo([suggest]), complemento([that, cultured, progenitors, are, able, to, circumvent, the, effects, of, the, 'DeltadblGATA', ablation, by, using, a, 'second,', more, 'proximal,', promoter, and, use, this, mechanism, to, generate, quantities, of, 'GATA-1', that, will, support, eosinophil, growth, and, differentiation])]). relacion([sujeto(['However,', the, cellular, 'sources,']), verbo([target]), complemento(['cells,', and, underlying, mechanisms, remain, elusive, in, humans])]). relacion([sujeto(['We', demonstrate, that, human, 'Th2', memory, cells]), verbo([expressing]), complemento([distinctive, levels, of, 'IL-25', receptor, '(', 'R)', are, one, of, the, responding, cell, types])]). relacion([sujeto(['IL-25']), verbo([promotes]), complemento([cell, expansion, and, 'Th2', cytokine, production, when, 'Th2', central, memory, cells, are, stimulated, with, thymic, stromal, lymphopoietin, '(', 'TSLP)-activated', dendritic, cells, '(', 'DCs),', homeostatic, 'cytokines,', or, 'T', cell, receptor, for, antigen, triggering])]). relacion([sujeto(['The']), verbo([enhanced]), complemento([functions, of, 'Th2', memory, cells, induced, by, 'IL-25', are, associated, with, sustained, expression, of, 'GATA-3,', 'c-MAF,', and, 'JunB', in, an, 'IL-4-independent', manner])]). relacion([sujeto(['Although', 'keratinocytes,', mast, 'cells,', 'eosinophils,', and, basophils]), verbo([express]), complemento(['IL-25', 'transcripts,', activated, eosinophils, and, basophils, from, normal, and, atopic, subjects, were, found, to, secrete, bioactive, 'IL-25', 'protein,', which, augments, the, functions, of, 'Th2', memory, cells])]). relacion([sujeto(['Our', results]), verbo([provide]), complemento([a, plausible, explanation, that, 'IL-25', produced, by, innate, effector, eosinophils, and, basophils, may, augment, the, allergic, inflammation, by, enhancing, the, maintenance, and, functions, of, adaptive, 'Th2', memory, cells])]). relacion([sujeto(['We']), verbo([found]), complemento([that, p63, binds, and, transactivate, 'GATA-3', 'promoter,', which, in, turn, transactivate, 'IKKalpha,', two, pivotal, regulators, of, epithelial, development])]). relacion([sujeto(['Concomitance', of, allergic, rhinitis, with, chronic, rhinosinusitis, further]), verbo([increased]), complemento([expression, of, 'GATA-3,', and, subsequently, enhanced, 'IL-5', expression])]). relacion([sujeto(['The', present, study, underlines, the, importance, of, 'gemfibrozil,', a, 'lipid-lowering', drug, and, an, activator, of, peroxisome, 'proliferator-activated', 'receptor-alpha', '(', 'PPAR-alpha),', in]), verbo([inhibiting]), complemento([the, disease, process, of, adoptively, transferred, experimental, allergic, encephalomyelitis, '(', 'EAE),', an, animal, model, of, 'relapsing-remitting', multiple, sclerosis])]). relacion([sujeto(['Gemfibrozil', also]), verbo([inhibited]), complemento([the, encephalitogenicity, of, 'MBP-primed', 'T', cells, and, switched, the, immune, response, from, a, 'Th1', to, a, 'Th2', profile, independent, of, 'PPAR-alpha'])]). relacion([sujeto(['Gemfibrozil', consistently]), verbo([inhibited]), complemento([the, expression, and, 'DNA-binding', activity, of, 'T-bet,', a, key, regulator, of, 'interferon-gamma', '(', 'IFN-gamma)', expression, and, stimulated, the, expression, and, 'DNA-binding', activity, of, 'GATA3,', a, key, regulator, of, 'IL-4'])]). relacion([sujeto(['Gemfibrozil', treatment]), verbo([decreased]), complemento([the, number, of, 'T-bet-positive', 'T', cells, and, increased, the, number, of, 'GATA3-positive', 'T', cells, in, spleen, of, donor, mice])]). relacion([sujeto(['Although', excess, 'NO', favored, the, expression, of, 'T-bet,', scavenging, of, 'NO']), verbo([stimulated]), complemento([the, expression, of, 'GATA-3'])]). relacion([sujeto(['Taken', 'together,', our, results]), verbo([suggest]), complemento(['gemfibrozil,', an, approved, drug, for, hyperlipidemia, in, 'humans,', may, find, further, therapeutic, use, in, multiple, sclerosis])]). relacion([sujeto(['Human', natural, killer, '(', 'NK)', cells, are, the, key, contributors, of, innate, immune, response, and, the, effector, functions, of, these, cells, are]), verbo([enhanced]), complemento([by, cytokines, such, as, interleukine, 2, '(', 'IL2)'])]). relacion([sujeto(['We', utilized, 'genome-wide', transcriptional, profiling, to, identify, gene, expression, signatures, and, pathways, in, resting, and, 'IL2']), verbo([activated]), complemento(['NK', cell, isolated, from, peripheral, blood, of, healthy, donors])]). relacion([sujeto(['Gene', expression, profiling, of, resting, 'NK', cells, showed, high, expression, of, a, number, of, cytotoxic, 'factors,', 'cytokines,', chemokines, and, inhibitory, and]), verbo([activating]), complemento([surface, 'NK', receptors])]). relacion([sujeto(['Resting', 'NK', cells]), verbo([expressed]), complemento([many, genes, associated, with, cellular, quiescence, and, also, appeared, to, have, an, active, 'TGFbeta', '(', 'TGFB1)', signaling, pathway])]). relacion([sujeto(['IL2', stimulation]), verbo([induced]), complemento([rapid, downregulation, of, quiescence, associated, genes, and, upregulation, of, genes, associated, with, cell, cycle, progression, and, proliferation])]). relacion([sujeto(['Numerous', genes, that, may]), verbo([enhance]), complemento([immune, function, and, responsiveness, including, activating, receptors, '(', 'DNAM1,', 'KLRC1', and, 'KLRC3),', death, receptor, ligand, '(', 'TNFSF6', '(', 'FASL)', and, 'TRAIL),', chemokine, receptors, '(', 'CX3CR1,', 'CCR5', and, 'CCR7),', interleukin, receptors, '(', 'IL2RG,', 'IL18RAB', and, 'IL27RA)', and, members, of, secretory, pathways, '(', 'DEGS1,', 'FKBP11,', 'SSR3,', 'SEC61G', and, 'SLC3A2)', were, upregulated])]). relacion([sujeto(['The', expression, profile]), verbo([suggested]), complemento(['PI3K/AKT', activation, and, 'NF-kappaB', activation, through, multiple, pathways, '(', 'TLR/IL1R,', 'TNF', receptor, induced, and, 'TCR-like', possibly, involving, 'BCL10)'])]). relacion([sujeto(['Activation', of, 'NFAT', signaling, was, supported, by]), verbo([increased]), complemento([expression, of, many, pathway, members, and, downstream, target, genes])]). relacion([sujeto(['The', transcription, factor, 'GATA3', was]), verbo([expressed]), complemento([in, resting, cells, while, 'T-BET', was, upregulated, on, activation, concurrent, with, the, change, in, cytokine, expression, profile])]). relacion([sujeto(['The', importance, of, 'NK', cells, in, innate, immune, response, was, also, reflected, by, late]), verbo([increased]), complemento([expression, of, inflammatory, chemotactic, factors, and, receptors, and, molecules, involved, in, adhesion, and, lymphocyte, trafficking, or, migration])]). relacion([sujeto(['Signalling', lymphocytic, activation, molecule, '(', 'SLAM)', and, interleukin, '(', 'IL)-18']), verbo([induce]), complemento([interferon, '(', 'IFN)-gamma', production, from, 'Th1', cells])]). relacion([sujeto(['The', 'allergen-induced', 'SLAM', and, 'IL-18', mRNA, expressions, are]), verbo([increased]), complemento([during, subcutaneous, immunotherapy, '(', 'SCIT),', but, nothing, is, known, about, their, role, during, sublingual, immunotherapy, '(', 'SLIT)'])]). relacion([sujeto(['Transcription', factor, 'GATA-3', is]), verbo([associated]), complemento([with, 'Th2', cells, but, its, role, in, 'SCIT', and, 'SLIT', is, yet, unexplored])]). relacion([sujeto(['This', study, was, undertaken, to, analyse, the, allergen]), verbo([induced]), complemento([in, vitro, mRNA, expression, of, 'IL-18,', 'SLAM', and, 'GATA-3', in, peripheral, blood, mononuclear, cells, '(', 'PBMC)', of, children, with, allergic, rhinitis, '(', 'AR)', during, 'SLIT'])]). relacion([sujeto(['Peripheral', blood, mononuclear, cell, were]), verbo([stimulated]), complemento([with, birch, extract, prior, 'to,', after, 1, and, 2, years, of, the, treatment])]). relacion([sujeto(['The', expression, of, 'IL-18', mRNA, was]), verbo([increased]), complemento([in, the, 'high-dose', group, in, comparison, to, the, placebo, group, after, 1, year, of, therapy, '(', 'P', =, 0.028, ')', and, had, an, inverse, correlation, with, the, late, phase, skin, reaction, after, the, second, study, year, '(', r, =, -, 0.41, ',', 'P', =, 0.041, ')'])]). relacion([sujeto(['SLAM', mRNA, expression]), verbo([increased]), complemento([in, the, 'high-dose', group, from, baseline, to, 1, year, '(', 'P', =, 0.028, ')', and, correlated, with, 'IL-10', '(', r, =, 0.96, ',', 'P', &, 'lt;', 0.0001, ')', and, transforming, growth, 'factor-beta', '(', r, =, 0.8, ',', 'P', =, 0.0037, ')', mRNA, expression])]). relacion([sujeto(['During', 'SLIT,', 'IL-18', and, 'SLAM', are, 'upregulated,']), verbo([suggesting]), complemento([that, the, 'Th2', type, inflammatory, response, is, downregulated, during, 'SLIT', by, increased, 'Th1', type, response])]). relacion([sujeto(['The', transcription, factor, 'GATA-3', is]), verbo([required]), complemento([for, normal, mammary, gland, 'development,', and, its, expression, is, highly, correlated, with, estrogen, receptor, alpha, '(', 'ER', 'alpha)', in, human, breast, tumors])]). relacion([sujeto(['Here,', we, show, that, 'GATA-3', is]), verbo([required]), complemento([for, estradiol, stimulation, of, cell, cycle, progression, in, breast, cancer, cells])]). relacion([sujeto(['The', role, of, 'GATA-3', in, estradiol, signaling]), verbo([requires]), complemento([the, direct, positive, regulation, of, the, expression, of, the, 'ER', alpha, gene, itself, by, 'GATA-3'])]). relacion([sujeto(['GATA-3']), verbo([binds]), complemento([to, two, 'cis-regulatory', elements, located, within, the, 'ER', alpha, 'gene,', and, this, is, required, for, 'RNA', polymerase, 'II', recruitment, to, 'ER', alpha, promoters])]). relacion([sujeto(['Reciprocally,', 'ER', alpha, directly]), verbo([stimulates]), complemento([the, transcription, of, the, 'GATA-3', 'gene,', indicating, that, these, two, factors, are, involved, in, a, positive, 'cross-regulatory', loop])]). relacion([sujeto(['Moreover,', 'GATA-3', and, 'ER', alpha]), verbo([regulate]), complemento([their, own, expression, in, breast, cancer, cells])]). relacion([sujeto(['Here,', overexpression, of, 'GATA-3', blocked, the, survival, of, 'pro-T', cells, when, 'Notch-Delta', signals, were, present, but]), verbo([enhanced]), complemento([viability, in, their, absence])]). relacion([sujeto(['In', fetal, thymocytes, at, the, 'double-negative', 1, '(', 'DN1)', stage, and, 'DN2', stage, but, not, those, at, the, 'DN3', 'stage,', overexpression, of, 'GATA-3', rapidly]), verbo([induced]), complemento([respecification, to, the, mast, cell, lineage, with, high, frequency, by, direct, transcriptional, '\'', 'reprogramming\''])]). relacion([sujeto(['Our', results]), verbo([suggest]), complemento([a, close, relationship, between, the, 'pro-T', cell, and, mast, cell, programs, and, a, previously, unknown, function, for, 'Notch', in, 'T', lineage, fidelity])]). relacion([sujeto(['Notch', signaling]), verbo([activates]), complemento(['T', lineage, differentiation, from, hemopoietic, 'progenitors,', but, relatively, few, regulators, that, initiate, this, program, have, been, 'identified,', e])]). relacion([sujeto(['Over', 90, genes, of, interest, were, 'identified,', and, 35, of, 44, tested, were, confirmed, to, be, more, highly]), verbo([expressed]), complemento([in, 'T', lineage, precursors, relative, to, precursors, of, 'B', 'and/or', myeloid, lineage])]). relacion([sujeto(['The', few, genes, sharply, 'up-regulated', between, multipotent, progenitors, and, 'Pro-T', cell, stages, included, those, encoding, transcription, factors, 'Bcl11b,', 'TCF-1', '(', 'Tcf7),', and, 'HEBalt,', 'Notch']), verbo([target]), complemento(['Deltex1,', 'Deltex3L,', 'Fkbp5,', 'Eva1,', and, 'Tmem131'])]). relacion([sujeto(['Bcl11b', was, uniquely, 'T', lineage, restricted, and]), verbo([induced]), complemento([by, 'Notch/Delta', signaling, specifically, upon, entry, into, the, 'T', lineage, differentiation, pathway])]). relacion([sujeto(['In', precultured, 'CD34+CD38-', 'CB', 'cells,', 'TNF']), verbo([increased]), complemento(['GATA3', but, decreased, 'EBF1', 'expression,', in, line, with, the, skewed, lymphoid, differentiation, induced, by, 'TNF'])]). relacion([sujeto(['After', 'short-term', culture, of, 'CD34+', 'CB', cells, in, the, presence, of, 'TNF,', 'T-cell', generation, is]), verbo([stimulated]), complemento([at, the, expense, of, 'B-cell', generation])]). relacion([sujeto(['These', results]), verbo([have]), complemento([implications, on, the, culture, conditions, to, be, used, for, 'CB', 'CD34+', cells, prior, to, transplantation])]). relacion([sujeto(['Regulatory', 'T', cells, '(', 'T-reg', 'cells)']), verbo([have]), complemento([been, described, as, an, important, cell, population, in, the, 'UV', treatment, of, inflammatory, skin, diseases])]). relacion([sujeto(['We']), verbo([have]), complemento([treated, five, patients, with, generalized, atopic, eczema, '(', 'AE)', using, 'medium-dose', '(', 15, cycles, of, 50, 'J/cm(2),', total, dose, of, 750, 'J/cm(2))', 'UVA1', therapy, and, have, analyzed, the, 'skin-infiltrating', 'T-cellular', subsets, before, and, after, therapy])]). relacion([sujeto(['However,', we, did, not, observe, a, general]), verbo([decrease]), complemento([in, 'T', cell, numbers])]). relacion([sujeto(['These', results, were, paralleled, by, 'RT-PCR', for, 'IL-10', and, staining, for, 'CD152,', a, surface, molecule, that]), verbo([has]), complemento([been, described, for, 'T-reg', cells])]). relacion([sujeto(['We']), verbo([have]), complemento([previously, characterized, the, 'Mexican', axolotl, '(', 'Ambystoma', 'mexicanum)', 'T', cell, receptor, delta, '(', 'TRD)', chain])]). relacion([sujeto(['Our', results]), verbo([suggest]), complemento([that, gammadelta, 'T', cells, that, express, the, canonical, 'TRDV1S1-TRDJ1', transcript, emerge, from, the, thymus, and, colonize, the, peripheral, 'tissues,', where, they, are, selectively, expanded, by, recurrent, ligands])]). relacion([sujeto(['In', thymectomized, 'axolotls,', 'TRD', repertoires, appear, different, from, those, of, normal, 'axolotls,']), verbo([suggesting]), complemento([that, extrathymic, gammadelta, 'T', cell, differentiation, could, occur])]). relacion([sujeto(['Some', polyacetylenes, from, the, plant, 'Bidens', pilosa]), verbo([have]), complemento([been, reported, to, treat, diabetes])]). relacion([sujeto(['In', this, 'study,', we]), verbo([report]), complemento([that, the, cytopiloyne, from, 'B'])]). relacion([sujeto(['pilosa,', which, is, structurally, different, from, the, 'above-mentioned', polyacetylenes, and]), verbo([inhibits]), complemento(['CD4(+)', 'T', cell, 'proliferation,', effectively, prevents, the, development, of, diabetes, in, nonobese, diabetic, mice, as, evidenced, by, a, normal, level, of, blood, glucose, and, insulin, and, normal, pancreatic, islet, architecture])]). relacion([sujeto(['Cytopiloyne', also]), verbo([suppresses]), complemento([the, differentiation, of, type, 1, 'Th', cells, but, promotes, that, of, type, 2, 'Th', 'cells,', which, is, consistent, with, it, enhancing, 'GATA-3', transcription])]). relacion([sujeto(['Also,', 'long-term', application, of, cytopiloyne, significantly]), verbo([decreases]), complemento([the, level, of, 'CD4(+)', 'T', cells, inside, pancreatic, lymph, nodes, and, spleens, but, does, not, compromise, total, 'Ab', responses, mediated, by, 'T', cells])]). relacion([sujeto(['Coculture', assays, imply, that, this]), verbo([decrease]), complemento([in, 'CD4(+)', 'T', cells, involves, the, 'Fas', 'ligand/Fas', pathway])]). relacion([sujeto(['Overall,', our, results]), verbo([suggest]), complemento([that, cytopiloyne, prevents, type, 1, diabetes, mainly, via, 'T', cell, regulation])]). relacion([sujeto(['Cross-talk', between, 'TGF-beta', and, 'IL-6']), verbo([has]), complemento([been, shown, to, direct, the, differentiation, of, 'CD4(+)', cells, into, special, 'IL-17-secreting', 'cells,', which, are, termed, 'Th17', cells])]). relacion([sujeto(['In', this, 'study,', we, demonstrated, that, 'TGF-beta', and, 'IL-6', could]), verbo([stimulate]), complemento(['CD8(+)', cells, to, differentiate, into, 'noncytotoxic,', 'IL-17-producing', cells, in, 'MLC'])]). relacion([sujeto(['The', mRNA, level, of, 'Th2/T', cytotoxic, 2, '(', 'Tc2)', transcription, factors, 'GATA3', and, 'Th1/Tc1', transcription, factors, 'T-box']), verbo([expressed]), complemento([in, 'T', cell, '(', 'T-bet)', as, well, as, its, target, 'H2'])]). relacion([sujeto(['O-like', homeobox, '(', 'Hlx)', is]), verbo([decreased]), complemento([in, 'CD8(+)', cells, from, 'TGF-beta-', and, 'IL-6-treated', 'MLC'])]). relacion([sujeto(['Following', rectal, oxazolone, 'instillation,', 'Th2', cells, producing, 'IL-13']), verbo([induce]), complemento([a, progressive, colitis, resembling, human, ulcerative, colitis])]). relacion([sujeto(['The', therapeutic, effects, of, 'FTY720', were]), verbo([associated]), complemento([with, a, prominent, reduction, of, the, key, effector, 'Th2', cytokines, 'IL-13,', 'IL-4', and, 'IL-5'])]). relacion([sujeto(['Strikingly,', 'FTY720']), verbo([inhibited]), complemento(['GATA3', and, 'T1/ST2', expression, which, represent, highly, relevant, markers, for, 'Th2', differentiation, and, 'Th2', effector, 'function,', respectively])]). relacion([sujeto(['Our', data]), verbo([provide]), complemento([the, first, evidence, that, 'FTY720', exhibits, beneficial, prophylactic, as, well, as, therapeutic, effects, in, 'Th2-mediated', experimental, colitis, by, directly, affecting, 'Th2', cytokine, profiles, probably, by, reducing, 'T1/ST2,', thus, offering, a, new, auspicious, therapeutic, instrument, for, the, treatment, of, human, ulcerative, colitis])]). relacion([sujeto(['Nectins', are, cell, adhesion, molecules]), verbo([involved]), complemento([in, the, regulation, of, epithelial, physiology])]). relacion([sujeto(['We', present, here, 'Nectin-4/PVRL4', as, a, new, histological, and, serological, tumor]), verbo([associated]), complemento([marker, for, breast, carcinoma])]). relacion([sujeto(['By', 'contrast,', 'Nectin-4', was]), verbo([expressed]), complemento([in, 61, '%', of, ductal, breast, carcinoma, vs, 6, '%', in, lobular, type])]). relacion([sujeto(['All', but, one, 'ER/PR-negative', tumors]), verbo([expressed]), complemento(['Nectin-4'])]). relacion([sujeto(['Nectin-4', emerges, as, a, potential]), verbo([target]), complemento([for, breast, cancer, immunotherapy])]). relacion([sujeto(['T', and, 'B', cells, must, also, decide, whether, or, not, to]), verbo([respond]), complemento([to, antigen, and, when, a, response, is, 'initiated,', what, sort, of, response, to, make, such, as, the, type, of, 'antibody,', 'CD4', or, 'CD8,', and, 'CD4', 'Th1', or, 'Th2'])]). relacion([sujeto(['Selection', depends, on, prior, stochastic, production, of, precommitted, 'cells,', which, are, then, selected, to]), verbo([respond]), complemento([by, an, appropriate, 'signal;', for, 'example,', 'CD8', and, 'CD4', responses, selected, by, peptide, presented, in, association, with, major, histocompatibility, complex, class, 'I', or, 'II'])]). relacion([sujeto(['In', this, 'paper,', the, signals, that, determine, 'Th1', and, 'Th2', differentiation, are, examined, with, a, mathematical, model, and, shown, to]), verbo([act]), complemento([as, a, bistable, switch, permitting, either, 'Tbet', or, 'Gata3', to, be, expressed, in, an, individual, cell, but, not, both])]). relacion([sujeto(['The', model, is, used, to, show, how, the, 'Tbet', 'Gata3', network, within, an, individual, cell]), verbo([interacts]), complemento([with, cytokine, signals, between, cells, and, suggests, how, 'Th1', and, 'Th2', lineage, commitment, can, become, irreversible])]). relacion([sujeto(['These', considerations]), verbo([provide]), complemento([an, example, of, how, mathematical, models, can, be, used, to, gain, a, better, understanding, of, lymphocyte, differentiation, in, an, immune, response])]). relacion([sujeto(['Previous', studies, revealed, several, substrate, proteins, of, 'Chk1', and, 'Chk2,', but, identification, of, additional]), verbo([targets]), complemento([is, still, important, in, order, to, understand, their, tumor, suppressor, functions])]). relacion([sujeto(['In', this, 'study,', we, screened, novel, substrates, for, 'Chk1', and, 'Chk2', using, substrate]), verbo([target]), complemento([motifs, determined, previously, by, an, oriented, peptide, library, approach])]). relacion([sujeto(['Immunoprecipitation', kinase, assay, of, 'full-length', proteins, and, 'site-directed', mutagenesis, analysis, of, the]), verbo([target]), complemento([motifs, demonstrated, that, 'HDAC5', and, 'PGC-1alpha', were, specific, targets, for, 'Chk1', 'and/or', 'Chk2', at, least, in, vitro])]). relacion([sujeto(['Together', with, our, prior, studies, on, renal, neoplasms, and, normal, 'kidney,', these, studies]), verbo([suggested]), complemento([that, the, gene, for, placental, 'S100', '(', 'S100P)', is, specifically, expressed, in, benign, and, malignant, urothelial, cells])]). relacion([sujeto(['Rosiglitazone', could]), verbo([regulate]), complemento([the, balance, of, 'IFN-gamma', and, 'IL-4', through, effect, on, the, expression, of, 'T-bet', mRNA, and, 'GATA-3', mRNA])]). relacion([sujeto(['There', are, a, predominant, expression, of, 'GATA-3', and, 'T-bet,', but, a]), verbo([decreased]), complemento([expression, of, 'FOXP3', in, 'Df-stimulated', 'PBMCs', from, patients, with, asthma])]). relacion([sujeto(['(', 3, ')', 'Numbers', of, cells]), verbo([expressing]), complemento(['GATA-3', mRNA, correlated, significantly, with, 'T-bet', mRNA, positive, cell, numbers, in, decidua, '(', r, =, -, 0.55, ',', 'P', &, 'lt;', 0.01, ')'])]). relacion([sujeto(['The', results, demonstrate, that, upregulated, expression, of, 'T-bet', and, downregulated, expression, of, 'GATA-3', are]), verbo([found]), complemento([in, the, decidua, of, women, with, 'URSA'])]). relacion([sujeto(['Imbalance', of, 'GATA-3/T-bet', transcription, factors, might, interfere, with, type, 1, helper, 'T', cell, '(', 'Th1)/type', 2, helper, 'T', cell, '(', 'Th2)', differentiation, at, the, 'fetal-maternal', interface, and]), verbo([cause]), complemento(['URSA'])]). relacion([sujeto(['Although', tight, regulation, of, transcription, factor, expression, appears, to, be, 'essential,', little, is, known, about, the, epigenetic, mechanisms]), verbo([involved]), complemento([in, transcription, factor, gene, regulation])]). relacion([sujeto(['We']), verbo([have]), complemento([analyzed, 'DNA', methylation, profiles, of, 13, key, transcription, factor, genes, in, primary, cells, of, the, hematopoietic, 'cascade,', lymphoma, cell, lines, and, lymph, node, biopsies, of, diffuse, large, 'B-cell-', and, 'T-cell-non-Hodgkin', lymphoma, patients])]). relacion([sujeto(['For', some, 'genes,', such, as, 'SPI1,', 'Etv5', and, 'Eomes,', we]), verbo([found]), complemento([an, inverse, correlation, between, the, methylation, of, the, 5, '\'', untranslated, region, and, expression, of, the, associated, gene, suggesting, that, these, genes, are, regulated, by, 'DNA', methylation])]). relacion([sujeto(['Our', results]), verbo([suggest]), complemento([that, epigenetic, remodelling, of, transcription, factor, genes, is, a, frequent, mechanism, during, hematopoietic, development])]). relacion([sujeto(['Aberrant', methylation, of, transcription, factor, genes, is, frequently, observed, in, diffuse, large, 'B-cell', lymphomas, and, might]), verbo([have]), complemento([a, functional, role, during, tumorigenesis])]). relacion([sujeto(['Sphingosine', 1, -, phosphate, '(', 'S1P)', is, a, natural, lipid, mediator, that]), verbo([regulates]), complemento([immune, cell, 'traffic,', 'Ab', 'production,', and, 'T', cell, cytokine, generation, by, mechanisms, that, enhance, 'Th2', activities])]). relacion([sujeto(['The', production, of, 'IL-4,', but, not, 'IL-2', or, 'IFN-gamma,', was, significantly, 'up-regulated', &, 'gt;10-fold', in]), verbo([activated]), complemento(['CD4', 'T', cells, from, 'S1P(1)', 'TG', mice, compared, with, those, from, 'wild-type', mice])]). relacion([sujeto(['The', 'up-regulation', of, 'IL-4', mRNA, was]), verbo([mediated]), complemento([by, 'c-Maf,', 'Jun', 'B,', and, 'Gata3', as, demonstrated, by, increases, in, their, protein, expression, and, 'DNA-binding', activities])]). relacion([sujeto(['Immunological', assays, showed, that]), verbo([increased]), complemento(['IL-4', levels, induced, greater, production, of, 'IgE'])]). relacion([sujeto(['Thus,', the, 'S1P-S1P(1)', axis, specifically, 'up-regulates', 'c-Maf,', 'Jun', 'B,', and, 'Gata3,', which, consequently]), verbo([enhance]), complemento(['IL-4', production, that, may, lead, to, a, 'Th2', phenotype])]). relacion([sujeto(['We', believe, that, immunotherapy, with, 'HKL', as, an, adjuvant]), verbo([induces]), complemento(['Thl-like', 'TReg', cells, that, can, inhibit, 'AHR', and, airway, inflammation])]). relacion([sujeto(['These', 'antigen-specific', 'TReg', cells, are]), verbo([induced]), complemento([with, 'CD8alpha+', 'DCs', producing, 'IL-12', and, 'IL-10,', produce, 'IFN-gamma', and, 'IL-10,', and, also, express, 'T-bet', and, 'Foxp3'])]). relacion([sujeto(['These', 'Th1Reg', cells, are, distinct, from, 'antigen-specific', 'TReg', cells]), verbo([induced]), complemento([with, respiratory, 'tolerance,', which, can, also, inhibit, 'AHR', and, airway, inflammation])]). relacion([sujeto(['These', 'Th2-like', 'TReg', cells, are]), verbo([induced]), complemento([with, 'CD8alpha-', 'DCs', producing, 'IL-10,', they, express, 'IL-10,', 'GATA3', and, 'Foxp3'])]). relacion([sujeto(['So', allergen, immunotherapy, is, effective, in, large, part, because, it]), verbo([induces]), complemento([regulatory, 'T', cells])]). relacion([sujeto(['We', believe, that, with, further, 'refinements,', allergen, immunotherapy, that, rapidly]), verbo([induces]), complemento([allergen, specific, 'TReg', cells, will, indeed, be, the, magic, bullets, for, allergy, and, asthma])]). relacion([sujeto(['WNT', family, members, are, 'secreted-type', glycoproteins]), verbo([regulating]), complemento([cell, 'fate,', planar, cell, 'polarity,', cell, 'adhesion,', and, cell, movement])]). relacion([sujeto(['Although', 'WNT8B', is, undetectable, in, normal, adult, tissues, by, using, 'Northern', blot, 'analyses,', 'WNT8B', is]), verbo([expressed]), complemento([in, gastric, 'cancer,', pancreatic, 'cancer,', colorectal, 'cancer,', breast, 'cancer,', and, embryonal, tumors])]). relacion([sujeto(['Cow', 'Wnt8b', complete, coding, sequence, was]), verbo([found]), complemento([to, encode, a, 350, -, 'amino-acid', 'protein,', which, showed, 96.9, '%', 'total-amino-acid', identity, with, human, 'WNT8B'])]). relacion([sujeto(['Comparative', proteomics, revealed, that, 'N-terminal', signal, 'peptide,', 22, 'Cys', 'residues,', two, 'Asn-linked', glycosylation, 'sites,', 'Gly230,', and, 'Arg284', of, human, 'WNT8B', were]), verbo([conserved]), complemento([among, mammalian, 'WNT8B', orthologs])]). relacion([sujeto(['Comparative', genomics, revealed, that, 'POU/OCT-', and, 'GATA-binding', sites, in, the, 5, '\'', -, flanking, promoter, region, were]), verbo([conserved]), complemento([among, 'human,', 'chimpanzee,', 'cow,', 'mouse,', and, rat, 'WNT8B', orthologs])]). relacion([sujeto(['In', silico, expression, analyses, revealed, that, human, 'WNT8B', was]), verbo([expressed]), complemento([in, embryoid, body, derived, from, embryonic, stem, '(', 'ES)', 'cells,', hepatocyte, progenitors, derived, from, 'ES', 'cells,', fetal, 'brain,', 'diffuse-type', gastric, 'cancer,', colorectal, 'cancer,', prostate, 'cancer,', and, ovarian, fibrotheoma])]). relacion([sujeto(['Genomic', regulatory, networks, specify, how, cellular, gene, expression]), verbo([responds]), complemento([to, external, temporal, and, spatial, 'stimuli,', ensuring, that, correct, cell, fate, decisions, are, made, and, the, appropriate, cell, phenotypes, are, adopted])]). relacion([sujeto(['A', novel, role, for, 'Gata-3', in, specifying, and]), verbo([maintaining]), complemento([mammary, cell, fate, has, recently, been, identified])]). relacion([sujeto(['These']), verbo([reports]), complemento([offer, an, understanding, of, how, mammary, cells, assume, and, maintain, a, variety, of, cell, behaviours, and, 'functions,', and, how, a, mammary, cell, may, potentially, subvert, these, constraints, during, carcinogenesis])]). relacion([sujeto(['Here,', we, show, that, in, 'CD2-GATA3', transgenic, 'mice,', with, enforced, 'GATA3', expression, driven, by, the, 'CD2', 'promoter,', thymocytes]), verbo([have]), complemento([reduced, levels, of, 'CD5,', which, is, a, negative, regulator, of, 'TCR', signaling, participating, in, 'TCR', repertoire, 'fine-tuning'])]). relacion([sujeto(['Reduction', of, 'CD5', expression, was, most, prominent, in, 'CD4(+)CD8(+)', 'double-positive', '(', 'DP)', cells, and, was]), verbo([associated]), complemento([with, increased, levels, of, the, transcription, factor, 'E2A'])]). relacion([sujeto([10, also, manifested]), verbo([decreased]), complemento(['CD5', levels])]). relacion([sujeto(['As', in, these, 'TCR-transgenic', mice, reduced, 'CD5', expression, cannot, result, from, an, effect, of, 'GATA3', on, repertoire, 'selection,', we, conclude, that, enforced, 'GATA3', interferes, with, the, developmentally]), verbo([regulated]), complemento([increase, of, 'CD5', levels])]). relacion([sujeto([10, transgenic, mice, was, also, accompanied, by]), verbo([enhanced]), complemento(['TCR', expression, during, 'CD4', positive, selection])]). relacion([sujeto(['Because', 'GATA3', is]), verbo([induced]), complemento([by, 'TCR', signaling, in, 'DP', 'thymocytes,', our, findings, indicate, that, 'GATA3', establishes, a, positive, feedback, loop, that, increases, 'TCR', surface, expression, in, developing, 'CD4', lineage, cells])]). relacion([sujeto(['A', role, for, 'GATA-3', during, thymic, development]), verbo([has]), complemento([long, implied, by, its, continuous, and, regulated, expression, through, out, 'T', lineage, 'development,', but, the, absolute, requirement, for, 'GATA-3', during, early, 'T', lymphoid, 'commitment/survival', previously, precluded, definitive, answers, to, this, question])]). relacion([sujeto(['Several', technical, breakthroughs]), verbo([have]), complemento([fueled, fruitful, investigation, in, recent, years, and, uncovered, unexpected, and, critical, roles, for, 'GATA-3', in, 'CD4', thymocyte, 'survival,', invariant, natural, killer, 'T', cell, generation, and, 'function,', and, also, in, beta, selection])]). relacion([sujeto(['Not', only, does, 'GATA-3']), verbo([participate]), complemento([in, nearly, every, stage, of, 'T', cell, development, from, common, lymphoid, progenitor, to, 'Th2,', conditional, knockout, studies, have, indicated, that, the, influence, of, 'GATA-3', also, extends, beyond, the, immune, system])]). relacion([sujeto(['Chinese', herbs, for, tonifying, 'Shen', can, adjust, the, imbalance, of, 'Th1/Th2', in, multiple, layers, by]), verbo([enhancing]), complemento([the, function, of, 'Th1', cells, and, attenuating, the, function, of, 'Th2', 'cells,', which, may, be, realized, through, various, links, as, regulating, the, expression, of, transcription, factors, and, cytokines])]). relacion([sujeto(['Here,', we, test, whether, 'Gata2', and, -, 3, transgenes, rescue, the, erythroid, defect, of, 'Gata1-null', 'mice,', if]), verbo([expressed]), complemento([in, the, appropriate, spatiotemporal, pattern])]). relacion([sujeto(['The', dramatic]), verbo([increase]), complemento([of, endogenous, 'Gata2', mRNA, in, 'Gata1-null', progenitors, is, not, reflected, in, 'Gata2', protein, 'levels,', invoking, translational, regulation])]). relacion([sujeto(['Our', data, show, that, the, dynamic, spatiotemporal, regulation, of, 'Gata', factor, levels, is, more, important, than, their, identity, and]), verbo([provide]), complemento([a, paradigm, for, developmental, control, mechanisms, that, are, 'hard-wired', in, 'cis-regulatory', elements])]). relacion([sujeto([36, consecutive, patients, with, systemic, lupus, erythematosus, having, active, renal, disease, were, 'recruited,', and, they, were]), verbo([required]), complemento([to, undergo, kidney, biopsy])]). relacion([sujeto(['Intraglomerular', expression, of, certain]), verbo([target]), complemento([genes, correlate, with, the, severity, of, systemic, as, well, as, histological, 'activity,', whereas, the, tubulointerstitial, expression, of, other, target, genes, correlate, with, the, degree, of, chronic, kidney, scarring])]). relacion([sujeto(['T', helper, type, 2, '(', 'Th2)', cell, differentiation]), verbo([requires]), complemento([the, expression, of, 'GATA-3,', a, transcription, factor, that, allows, transcriptional, activation, of, 'Th2', cytokine, genes, through, chromatin, remodelling])]). relacion([sujeto(['Results', showed, that, in, vivo, 'CTLA-4', blockade]), verbo([enhanced]), complemento([the, 'Par', j, 'I-specific', immunoglobulin, 'E', '(', 'IgE)', serum, level])]). relacion([sujeto(['In', 'contrast,', 'Par', j, 'I-specific', 'IgG2a', serum, level, was, 'reduced,']), verbo([suggesting]), complemento([that, 'CTLA-4', blockade, skewed, immunoglobulin, production, towards, 'interleukin-4', '(', 'IL-4)', -, dependent, immunoglobulin, isotypes])]). relacion([sujeto(['Consistently,', 'CTLA-4', blockade]), verbo([increased]), complemento([the, frequency, of, 'Par', j, 'I-specific', 'Th2', cells, but, not, 'Th1', 'cells,', as, well, as, 'IL-4', and, 'IL-5', but, not, 'interferon-gamma', production])]). relacion([sujeto(['Our', data, also, showed, that, 'CTLA-4', blockade]), verbo([enhanced]), complemento([the, 'GATA-3', :, 'T-bet', messenger, 'RNA', ratio])]). relacion([sujeto(['Interestingly,', in, vivo, 'CTLA-4', blockade, did, not]), verbo([increase]), complemento([the, frequency, of, 'GATA-3', 'protein-expressing', cells])]). relacion([sujeto(['In', 'contrast,', it]), verbo([enhances]), complemento(['GATA-3', protein, level, per, cell])]). relacion([sujeto(['Further,', in, vitro, results, show, that, the, 'anti-CTLA-4', monoclonal, 'antibody,', by, competing, with, 'CD80', for, 'CTLA-4', 'binding,']), verbo([induced]), complemento([an, enhancement, in, the, frequency, of, 'IL-4-producing', cells, that, correlates, with, the, increase, in, 'GATA-3', protein, level, per, cell])]). relacion([sujeto(['In', 'conclusion,', 'CTLA-4,', by, affecting, the, level, of, 'GATA-3', per, 'cell,', contributes, to, keeping, this, factor, under, the, threshold]), verbo([required]), complemento([to, become, a, 'Th2', effector, cell])]). relacion([sujeto(['The', critical, role, for, 'GATA', family, proteins, in]), verbo([maintaining]), complemento([the, normal, '(', 'non-transformed)', cell, state, is, corroborated, by, the, recent, findings, of, mutations, or, methylation, in, 'GATA', genes, both, in, primary, cancers, and, tumor, lines, including, breast])]). relacion([sujeto(['Previously,', microarray, profiling, studies, determined, that, the, highest, expression, of, both, 'GATA3', and, 'ESR1', '(', estrogen, receptor, 'alpha)', is, seen, in, tumors]), verbo([associated]), complemento([with, the, most, favorable, survival, 'outcomes,', whereas, the, lowest, expression, of, 'GATA3', is, detected, in, tumor, subtypes, showing, the, worst, outcomes])]). relacion([sujeto(['At', this, 'time,', genes, and, pathways, that, are]), verbo([regulated]), complemento([by, 'GATA3', in, the, mammary, gland, are, not, well, defined])]). relacion([sujeto(['We']), verbo([have]), complemento([previously, established, a, requirement, for, 'FOG', '(', 'Friend', 'Of', 'GATA)', cofactors, during, mouse, development])]). relacion([sujeto(['Here', we]), verbo([report]), complemento([that, in, the, murine, mammary, gland, 'Fog2', gene, expression, is, upregulated, upon, pregnancy, and, lactation, with, prominent, expression, in, the, epithelial, cells, of, the, gland, during, 'post-lactational', regression])]). relacion([sujeto(['Mammary-specific', deletion, of, 'Fog2', identified, a, role, for, this, gene, during, gland, 'involution;', excision, of, the, 'Fog2', gene]), verbo([leads]), complemento([to, the, accelerated, involution, of, the, gland, despite, diminished, levels, of, the, remodeling, enzymes])]). relacion([sujeto(['The', 'Natural', 'Killer', cell, maturation, from, 'CD34(+)', hematopoietic, cell, precursors, is, a, complex, process, that]), verbo([requires]), complemento([the, synergistic, effect, of, different, cytokines, and, growth, factors])]). relacion([sujeto(['Although', there]), verbo([have]), complemento([been, a, number, of, important, advances, in, our, understanding, of, the, 'Natural', 'Killer', 'differentiation,', the, developmental, step, leading, to, mature, 'Natural', 'Killer', cells, is, still, poorly, defined])]). relacion([sujeto(['These', 'CD56(+)', cells, exerted, cytotoxic, activity, and]), verbo([expressed]), complemento([the, 'CD94', inhibitory, receptor])]). relacion([sujeto(['The', supplementation, with, zinc, greatly]), verbo([increased]), complemento([both, the, number, of, cells, in, culture, and, the, absolute, number, of, 'CD56(+)', cells])]). relacion([sujeto(['Zinc']), verbo([induced]), complemento([higher, levels, of, cytotoxic, activity, and, a, higher, number, of, 'perforin-producing', and, of, 'CD94-bearing', 'CD56(+)', cells, in, comparison, with, zinc, unsupplemented, cultures, in, early, stages, of, 'Natural', 'Killer', cell, development])]). relacion([sujeto(['The', 'zinc-induced', changes, in, 'CD34-derived', 'CD56(+)', cells, were]), verbo([associated]), complemento([with, an, increased, expression, of, 'GATA-3,', a, 'zinc-finger', transcription, factor, providing, for, maturation, and, activity, of, 'T', and, 'Natural', 'Killer', cells])]). relacion([sujeto(['The']), verbo([increase]), complemento([was, related, to, a, higher, 'CD56(+)', cell, number, '(', 10, microM, 'zinc),', or, to, an, increased, 'GATA-3', mRNA, transcription, in, 'CD56(+)', cells, '(', 20, microM, 'zinc)'])]). relacion([sujeto(['In', 'Th2', 'cells,', expression, of, the, cytokine, 'IL-10', is, also]), verbo([induced]), complemento([by, 'GATA-3'])]). relacion([sujeto(['In', 'Th1', 'cells,', 'IL-10', expression, is]), verbo([induced]), complemento([by, 'IL-12,', but, the, 'IL-10', gene, lacks, detectable, histone, acetylation])]). relacion([sujeto(['This']), verbo([finding]), complemento([defines, a, potential, 'anti-inflammatory', role, for, 'IL-12', in, 'Th1', recall, responses])]). relacion([sujeto(['While', in, primary, 'Th1', responses, 'IL-12', is]), verbo([required]), complemento([to, induce, expression, of, the, 'pro-inflammatory', cytokine, 'IFN-gamma,', in, secondary, 'Th1', responses, 'IFN-gamma', 're-expression', is, independent, of, 'IL-12,', which, still, is, able, to, induce, expression, of, the, 'anti-inflammatory', cytokine, 'IL-10'])]). relacion([sujeto(['Interleukin-12', '(', 'IL-12)', is, a, key, cytokine, for, the, development, of, 'T', helper, type, 1, '(', 'Th1)', 'responses;', 'however,', naïve, 'CD4(+)', 'T', cells, do, not]), verbo([express]), complemento(['IL-12Rbeta2,', and, are, therefore, unresponsive, to, 'IL-12'])]). relacion([sujeto(['We']), verbo([have]), complemento([examined, the, mechanisms, that, control, 'Th1-specific', expression, of, the, human, 'IL-12Rbeta2', gene, at, early, time, points, after, 'T-cell', stimulation])]). relacion([sujeto(['We']), verbo([have]), complemento([identified, a, 'Th1-specific', enhancer, element, that, binds, signal, transducer, and, activator, of, transcription, 4, '(', 'STAT4)', in, vivo, in, developing, 'Th1', but, not, 'Th2', cells])]). relacion([sujeto(['T-cell', receptor, '(', 'TCR)', signaling]), verbo([induced]), complemento([histone, hyperacetylation, and, recruitment, of, 'BRG1,', the, 'ATPase', subunit, of, the, 'SWI/SNF-like', 'BAF', chromatin, remodeling, 'complex,', to, the, 'IL-12Rbeta2', regulatory, regions, and, was, associated, with, 'low-level', gene, transcription, at, the, 'IL-12Rbeta2', locus])]). relacion([sujeto(['However,', 'high-level', 'IL-12Rbeta2', expression]), verbo([required]), complemento(['TCR', triggering, in, the, presence, of, 'IL-12'])]). relacion([sujeto(['GATA-3', plays, a, critical, role, in, allergic, diseases, by]), verbo([regulating]), complemento([the, release, of, cytokines, from, 'Th2', lymphocytes])]). relacion([sujeto(['However,', the, molecular, mechanisms]), verbo([involved]), complemento([in, the, regulation, of, 'GATA-3', in, human, 'T', lymphocytes, are, not, yet, understood])]). relacion([sujeto(['Using', small, interfering, 'RNA', to, knock, down, 'GATA-3,', we]), verbo([have]), complemento([demonstrated, its, critical, role, in, regulating, 'IL-4,', 'IL-5,', and, 'IL-13', release, from, a, human, 'T', cell, line])]). relacion([sujeto(['Specific', stimulation, of, 'T', lymphocytes, by, costimulation, of, 'CD3', and, 'CD28', to, mimic, activation, by, 'APCs']), verbo([induces]), complemento([translocation, of, 'GATA-3', from, the, cytoplasm, to, the, 'nucleus,', with, binding, to, the, promoter, region, of, 'Th2', cytokine, 'genes,', as, determined, by, chromatin, immunoprecipitation])]). relacion([sujeto(['GATA-3']), verbo([nuclear]), complemento([translocation, is, dependent, on, its, phosphorylation, on, serine, residues, by, p38, 'MAPK,', which, facilitates, interaction, with, the, nuclear, transporter, protein, 'importin-alpha'])]). relacion([sujeto(['This']), verbo([provides]), complemento([a, means, whereby, allergen, exposure, leads, to, the, expression, of, 'Th2', 'cytokines,', and, this, novel, mechanism, may, provide, new, approaches, to, treating, allergic, diseases])]). relacion([sujeto(['The', 'E2A', transcription, factors, are]), verbo([required]), complemento([for, normal, 'T', lymphopoiesis, and, to, prevent, 'T-lymphocyte', progenitor, transformation])]). relacion([sujeto(['Ectopic', expression, of, 'E2A', proteins, in, 'E2A-deficient', lymphomas, results, in, growth]), verbo([arrest]), complemento([and, 'apoptosis,', indicating, that, these, cells, remain, responsive, to, the, targets, of, 'E2A'])]). relacion([sujeto(['Here', we, identify, the, transcriptional, repressor, growth, factor, independent, 1, 'B', '(', 'Gfi1b)', as, a]), verbo([target]), complemento([of, 'E2A', that, promotes, growth, arrest, and, apoptosis, in, lymphomas])]). relacion([sujeto(['Gfi1b', expression, in, primary, 'T-lymphocyte', progenitors, is, dependent, on, 'E2A', and, excess, 'Gfi1b']), verbo([prevents]), complemento([the, outgrowth, of, 'T', lymphocyte, progenitors, in, vitro])]). relacion([sujeto(['Gfi1b', represses, expression, of, 'Gata3,', a, transcription, factor, whose, appropriate, regulation, is]), verbo([required]), complemento([for, survival, of, lymphomas, and, 'T-lymphocyte', progenitors])]). relacion([sujeto(['We', also, show, that, ectopic, expression, of, 'Gata3', in, lymphomas]), verbo([promotes]), complemento([expression, of, 'Gfi1b,', indicating, that, these, proteins, may, function, in, an, autoregulatory, loop, that, maintains, appropriate, levels, of, 'Gata3'])]). relacion([sujeto(['Therefore,', we, propose, that, 'E2A', proteins]), verbo([prevent]), complemento([lymphoma, cell, 'expansion,', at, least, in, part, through, regulation, of, 'Gfi1b', and, modulation, of, 'Gata3', expression])]). relacion([sujeto(['We']), verbo([report]), complemento([here, that, inhibition, of, 'HDAC', activity, by, 'Trichostatin', 'A', '(', 'TSA)', and, sodium, butyrate, '(', 'NaBu),', the, two, specific, 'HDAC', 'inhibitors,', resulted, in, the, elevation, of, both, endogenous, and, exogenous, activity, of, 'IL-5', promoter])]). relacion([sujeto(['We', demonstrated, that, both, the, mRNA, expression, and, protein, production, of, 'IL-5', were]), verbo([stimulated]), complemento([by, 'TSA', and, 'NaBu', treatments])]). relacion([sujeto(['ChIP', assays, showed, that, treatments, of, 'TSA', and, 'NaBu']), verbo([caused]), complemento([hyperacetylation, of, histones, 'H3', and, 'H4', on, 'IL-5', promoter, in, 'Jurkat', 'cells,', which, consequently, promoted, the, exogenous, luciferase, activity, driven, by, this, promoter])]). relacion([sujeto(['Moreover,', 'site-directed', mutagenesis, studies, showed, that, the]), verbo([binding]), complemento([sites, for, transcription, factors, 'NFAT,', 'GATA3', and, 'YY1', on, 'IL-5', promoter, were, critical, for, the, effects, of, 'TSA', and, 'NaBu,', suggesting, that, the, transcriptional, activation, of, 'IL-5', gene, by, these, inhibitors, was, achieved, by, affecting, 'HDAC', function, on, 'IL-5', promoter, via, transcription, factors])]). relacion([sujeto(['Naive', 'CD4(+)', 'T', cells, were]), verbo([reported]), complemento([to, produce, small, amounts, of, 'IL-4', in, 'vitro,', which, are, implicated, to, be, sufficient, to, initiate, 'T(h)2', response, in, vivo])]). relacion([sujeto(['We', demonstrated, the, effectiveness, of, this, method, by, showing, that, the]), verbo([responding]), complemento(['CD4(+)GFP(+)', cells, exhibited, an, activated, 'phenotype,', possessed, the, capacity, to, express, 'IL-5', and, 'IL-13,', but, not, 'IFN-gamma', 'mRNA,', and, showed, enhanced, levels, of, 'GATA3', and, 'c-maf', mRNA, expression])]). relacion([sujeto(['By', using, this, newly, established, 'method,', we, showed, that, the, majority, of]), verbo([responding]), complemento(['GFP(+)', cells, were, 'CD4(+)', 'T', cells])]). relacion([sujeto(['Our', study]), verbo([provides]), complemento([direct, ex, vivo, evidence, to, show, that, a, small, percent, of, 'CD4(+)', 'T', cells, that, have, no, previous, experience, of, antigenic, stimulation, might, produce, 'IL-4', to, initiate, 'T(h)2', response])]). relacion([sujeto(['Aberrancies', in, 'T-cell', polarization, including, expression, of, chemokine, receptors]), verbo([have]), complemento([been, reported, in, human, leucocyte, antigen, '(', 'HLA)', class, 'II', associated, autoimmune, 'diseases,', such, as, type, 1, diabetes, '(', 'T1D)', and, rheumatoid, arthritis])]). relacion([sujeto(['CB', lymphocytes, were]), verbo([stimulated]), complemento([with, phytohaemagglutinin, in, type, 1, '(', interleukin, '(', 'IL)-12,', 'anti-IL4)', or, type, 2, '(', 'IL-4,', 'anti-IL12)', cytokine, environment, for, 6, days])]). relacion([sujeto(['After', culture, of, 'CB', lymphocytes, in, type, 2, cytokine, environment, newborn, infants, carrying, 'DR4-DQ8', haplotype, '(', 'n=18)', showed, reduced, percentage, of, 'CD4', 'T', cells]), verbo([expressing]), complemento(['CCR4', '(', 'P=0', x, 9, ')', and, the, level, of, 'CCR4', mRNA, was, decreased, '(', 'P=0', x, 8, ')'])]). relacion([sujeto(['In', 'addition,', lower, secretion, of, 'IL-13', and, expression, of, 'GATA-3', in, 'CB', lymphocytes, cultured, in, type, 2, cytokine, environment, were]), verbo([found]), complemento([in, the, infants, with, 'DR4-DQ8', haplotype, '(', 'P=0', x, 20, and, 'P=0', x, 4, ',', 'respectively)', in, comparison, to, newborn, infants, without, 'DR4-DQ8', and, 'DR3-DQ2', haplotypes, '(', 'n=37)'])]). relacion([sujeto(['Poor', in, vitro, induction, of, type, 2, immune, responses, in, newborn, infants, with, 'DR4-DQ8', haplotype]), verbo([suggests]), complemento([that, the, 'HLA', genotype, associated, with, risk, of, autoimmunity, may, affect, the, 'T', cell, polarization, already, at, 'birth,', which, in, turn, may, contribute, to, the, risk, for, autoimmunity, later, in, life])]). relacion([sujeto(['Dendritic', cells, '(', 'DCs)']), verbo([activated]), complemento([through, 'TLRs', provide, a, potent, negative, signal, for, 'Th2', cell, development, that, is, independent, of, positive, signals, for, 'Th1', cell, development, such, as, 'IL-12', and, 'IFN-gamma'])]). relacion([sujeto(['In', this, study, we, demonstrate, that, the, ability, of, 'TLR-activated', 'DCs', to]), verbo([suppress]), complemento(['Th2', cell, development, is, 'Ag', 'dose-independent', and, unique, to, 'DCs', that, have, been, activated, through, 'TLRs', vs, by, cytokines])]). relacion([sujeto(['We', show, that, 'TLR-activated', 'DCs']), verbo([inhibit]), complemento([early, 'IL-4', production, by, 'CD4', 'T', cells, and, thus, inhibit, their, ability, to, subsequently, increase, 'GATA-3', expression, and, commit, to, the, 'Th2', lineage])]). relacion([sujeto(['Although', 'CD4', 'T', cells]), verbo([activated]), complemento([by, 'TLR-activated', 'DCs', make, 'IL-2,', they, are, not, capable, of, phosphorylating, 'STAT5', in, response, to, this, cytokine])]). relacion([sujeto(['Our', findings]), verbo([suggest]), complemento([that, 'DCs', provide, instructional, signals, for, 'T', cell, differentiation, before, 'cytokine-mediated', 'Th', cell, selection, and, outgrowth])]). relacion([sujeto(['GATA-3', and, 'T-box']), verbo([expressed]), complemento([in, 'T', cells, '(', 'T-bet)', play, central, roles, in, 'Th-cell', development, and, function])]). relacion([sujeto(['In', 'contrast,', it, is, not, clear, whether, these, genes, are]), verbo([regulated]), complemento([in, human, 'Th', cells])]). relacion([sujeto(['However,', 'GATA-3', was]), verbo([expressed]), complemento([at, significantly, higher, levels, in, human, 'IL-4-producing', cells, enriched, via, capture, with, monoclonal, antibodies, '(', 'mAbs)', against, the, 'PGD(2)', 'receptor,', 'CRTH2,', the, best, selective, 'Th2-cell', surface, marker, to, date])]). relacion([sujeto(['Along', with]), verbo([increased]), complemento(['IL-4', and, 'GATA-3,', 'CRTH2(+)', 'Th', cells, isolated, from, 'Th2-skewed', cultures, or, the, circulating, memory, pool, exhibited, markedly, decreased, 'IFN-gamma', and, 'T-bet', expression])]). relacion([sujeto(['Thus,', the, human, 'GATA-3', gene, is, not]), verbo([regulated]), complemento([in, response, to, polarizing, signals, that, are, sufficient, to, direct, 'Th2-specific', expression, in, mouse, cells])]). relacion([sujeto(['The', 'hypoparathyroidism-deafness-renal', '(', 'HDR)', dysplasia, syndrome, is, an, autosomal, dominant, disorder]), verbo([caused]), complemento([by, mutations, of, the, dual, zinc, finger, transcription, 'factor,', 'GATA3'])]). relacion([sujeto(['The', splice, site, mutation, was, demonstrated, to]), verbo([cause]), complemento([a, 'pre-mRNA', processing, abnormality, leading, to, the, use, of, an, alternative, acceptor, site, 8, bp, downstream, of, the, normal, 'site,', resulting, in, a, frameshift, and, prematurely, terminated, protein])]). relacion([sujeto(['Electrophoretic', mobility, shift, assays, '(', 'EMSAs)', revealed, three, classes, of, 'GATA3', 'mutations:', those, that]), verbo([lead]), complemento([to, a, loss, of, 'DNA', binding, which, represent, over, 90, '%', of, all, 'mutations,', and, involved, a, loss, of, the, 'carboxy-terminal', zinc, 'finger;', those, that, resulted, in, a, reduced, 'DNA-binding', 'affinity;', and, those, '(', e])]). relacion([sujeto(['Leu348Arg)', that, did, not, alter, 'DNA']), verbo([binding]), complemento([or, the, affinity, but, likely, altered, the, conformational, change, that, occurs, during, binding, in, the, 'DNA', major, groove, as, predicted, by, a, 'three-dimensional', modeling])]). relacion([sujeto(['These', results, elucidate, further, the, molecular, mechanisms, underlying, the, altered, functions, of, mutants, of, this, zinc, finger, transcription, factor, and, their, role, in]), verbo([causing]), complemento([this, developmental, anomaly])]). relacion([sujeto(['To']), verbo([gain]), complemento([insight, into, the, role, of, 'Gata-3', in, breast, epithelial, development, and, 'oncogenesis,', we, have, explored, its, normal, function, within, the, mammary, gland, by, conditionally, deleting, 'Gata-3', at, different, stages, of, development])]). relacion([sujeto(['We']), verbo([report]), complemento([that, 'Gata-3', has, essential, roles, in, the, morphogenesis, of, the, mammary, gland, in, both, the, embryo, and, adult])]). relacion([sujeto(['Through', the, discovery, of, a, novel, marker, '(', 'beta3-integrin)', of, luminal, progenitor, cells, and, their, 'purification,', we, demonstrate, that, 'Gata-3', deficiency]), verbo([leads]), complemento([to, an, expansion, of, luminal, progenitors, and, a, concomitant, block, in, differentiation])]). relacion([sujeto(['Remarkably,', introduction, of, 'Gata-3', into, a, stem, 'cell-enriched', population]), verbo([induced]), complemento([maturation, along, the, alveolar, luminal, lineage])]). relacion([sujeto(['These', studies]), verbo([provide]), complemento([evidence, for, the, existence, of, an, epithelial, hierarchy, within, the, mammary, gland, and, establish, 'Gata-3', as, a, critical, regulator, of, luminal, differentiation])]). relacion([sujeto(['Natural', killer, 'T', '(', 'NKT)', cells, are, a, subset, of, 'T', cells, that, help, potentiate, and]), verbo([regulate]), complemento([immune, responses])]). relacion([sujeto(['Although', human, 'NKT', cell, subsets, with, distinct, effector, functions]), verbo([have]), complemento([been, 'identified,', it, is, unclear, whether, the, effector, functions, of, these, subsets, are, imprinted, during, development, or, can, be, selectively, reprogrammed, in, the, periphery])]). relacion([sujeto(['We']), verbo([found]), complemento([that, neonatal, 'NKT', cells, are, predominantly, 'CD4+', and, express, higher, levels, of, 'CCR7', and, 'CD62L', and, lower, levels, of, 'CD94', and, 'CD161', than, adult, 'CD4+', or, 'CD4-', 'NKT', cell, subsets])]). relacion([sujeto(['Together,', these, results]), verbo([suggest]), complemento([that, neonatal, 'CD4+,', adult, 'CD4+,', and, adult, 'CD4-', 'NKT', may, represent, unique, states, of, maturation, and, that, some, functions, of, human, 'NKT', cells, may, be, developmentally, 'imprinted,', while, others, are, acquired, similar, to, conventional, 'T', cell, subsets, during, peripheral, maturation, and, differentiation])]). relacion([sujeto(['Given', the, potent, 'immuno-regulatory', functions, of, 'NKT', 'cells,', these, findings]), verbo([have]), complemento([important, implications, for, the, development, of, novel, 'NKT', 'cell-based', therapeutics, and, vaccines])]). relacion([sujeto(['D-pinitol']), verbo([has]), complemento([been, demonstrated, to, exert, 'insulin-like', and, 'anti-inflammatory', activities])]). relacion([sujeto(['In', this, 'study,', we]), verbo([have]), complemento([attempted, to, determine, whether, 'D-pinitol', regulates, 'Th1/Th2', cytokine, 'production,', 'T-bet', and, 'GATA-3', gene, expression, in, 'OVA-induced', asthma, model, mice])]). relacion([sujeto(['These', reactions, included, an]), verbo([increase]), complemento([in, the, number, of, eosinophils, in, bronchoalveolar, lavage, '(', 'BAL)', 'fluid,', an, increase, in, inflammatory, cell, infiltration, into, the, lung, tissue, around, blood, vessels, and, 'airways,', airway, luminal, 'narrowing,', and, the, development, of, airway, 'hyper-responsiveness', '(', 'AHR)'])]). relacion([sujeto(['Accordingly,', this, study, may]), verbo([provide]), complemento([evidence, that, 'D-pinitol', plays, a, critical, role, in, the, amelioration, of, the, pathogenetic, process, of, asthma, in, mice])]). relacion([sujeto(['These', findings]), verbo([provide]), complemento([new, insight, into, the, immunopharmacological, role, of, 'D-pinitol', in, terms, of, its, effects, in, a, murine, model, of, 'asthma,', and, also, broaden, current, perspectives, in, our, understanding, of, the, immunopharmacological, functions, of, 'D-pinitol'])]). relacion([sujeto(['The', differentiation, of, mouse, naïve, 'CD4', 'T', cells, into, type, 2, helper, '(', 'Th2)', cells, is, accompanied, by, chromatin, remodeling, at, the, nucleosomes]), verbo([associated]), complemento([with, the, 'IL-4,', 'IL-13', and, 'IL-5', genes])]). relacion([sujeto(['In', typical, 'individuals,', the, chromatin, remodeling, indicated, by, the, induction, of, 'hyper-acetylation', of, histone, 'H3', lysine, 9, and, 'hyper-methylation', of, histone, 'H3', lysine, 4, was]), verbo([induced]), complemento([at, the, whole, 'Th2', cytokine, gene, loci, in, developing, 'Th2', cells])]). relacion([sujeto(['Th2-cell', specific, chromatin, remodeling, was]), verbo([induced]), complemento([at, most, of, the, 'Th2', cytokine, gene, loci])]). relacion([sujeto(['In', parallel, with, the, induction, of, chromatin, 'remodeling,', 'GATA3', mRNA, was, preferentially]), verbo([expressed]), complemento([in, developing, 'Th2', 'cells,', whereas, 'T-bet,', 'HLX', and, 'ROG', mRNA, was, selectively, expressed, in, developing, 'Th1', cells])]). relacion([sujeto(['Hodgkin\'s', lymphoma, '(', 'HL)', is, characterised, by, an, ineffective, immune, response, that, is, predominantly]), verbo([mediated]), complemento([by, 'CD4+', 'T-cells'])]). relacion([sujeto(['To', analyse, the, expression, of, the, key, regulatory, 'T-cell', transcription, factors, '(', 'TFs)', in, the, 'T-cells', of, 'HL']), verbo([involved]), complemento([tissues, in, order, to, assess, the, nature, of, the, 'T(H)', immune, response, in, 'HL'])]). relacion([sujeto(['By', 'immunohistochemistry,', 'GATA3', was, strongly, and, 'T-bet', exclusively]), verbo([expressed]), complemento([in, a, subset, of, interfollicular, lymphocytes, in, the, reactive, lymphoid, tissues])]). relacion([sujeto(['Notably,', this, regenerative, process]), verbo([leads]), complemento([to, the, restoration, of, the, correct, patterning, of, hair, cell, phenotype, and, afferent, innervation, within, the, repaired, sensory, epithelium])]). relacion([sujeto(['The', molecular, signals, that, specify, cell, phenotype, and]), verbo([regulate]), complemento([neuronal, guidance, during, sensory, regeneration, are, not, 'known,', but, they, are, likely, to, be, similar, to, the, signals, that, direct, these, processes, during, embryonic, development])]). relacion([sujeto(['Cells', that]), verbo([express]), complemento([tenascin, begin, to, recover, after, about, 2, weeks, and, are, then, contacted, by, calyx, terminals, of, vestibular, neurons])]). relacion([sujeto(['In', 'addition,', our, previous, work, had, shown, that, the, zinc, finger, transcription, factor, 'GATA3', is, uniquely]), verbo([expressed]), complemento([within, the, striolar, reversal, zone, of, the, utricle, '(', 'Hawkins', et, al])]). relacion([sujeto(['[', 2003, ']', 'Hum', 'Mol', 'Genet', 12, :, 1261, -, 1272, ')', ',', and, we, show, here, that, this, regionalized, expression, of, 'GATA3', is]), verbo([maintained]), complemento([after, severe, hair, cell, lesions, and, after, transplantation, of, the, sensory, epithelium, onto, a, chemically, defined, substrate])]). relacion([sujeto(['These', observations]), verbo([suggest]), complemento([that, 'GATA3', expression, may, maintain, positional, information, in, the, maculae, during, sensory, regeneration])]). relacion([sujeto(['The', transcription, factor, 'Gata3', is, crucially]), verbo([involved]), complemento([in, epidermis, and, hair, follicle, differentiation])]). relacion([sujeto(['Yet,', little, is, known, about, how, 'Gata3', 'co-ordinates', stem, cell, lineage, determination, in, 'skin,', what, pathways, are]), verbo([involved]), complemento([and, how, 'Gata3', differentially, regulates, distinct, cell, populations, within, the, hair, follicle])]). relacion([sujeto(['Elucidation', of, these, pathways, at, the, 'RNA', and, protein, levels, and, physiologic, endpoints]), verbo([suggests]), complemento([that, 'Gata3', integrates, diverse, signaling, networks, to, regulate, the, balance, between, hair, follicle, and, epidermal, cell, fates])]). relacion([sujeto(['These', cells]), verbo([express]), complemento([markers, of, the, serotonin, lineage, such, as, the, 'rate-limiting', enzyme, in, serotonin, 'synthesis,', tryptophan, hydroxylase, 2, ',', the, serotonin, 'transporter,', and, the, transcription, factor, 'Pet1'])]). relacion([sujeto(['These', cells, are, generated, in, rhombomeres, 'r1-r3', and, 'r5-r7', caudal, to, the, 'midbrain-', hindbrain, organizer, under, the, control, of, the, fibroblast, growth, factors, 4, and, 8, and, sonic, hedgehog, '(', 'SHH)', from, 'precursors,', which]), verbo([have]), complemento([produced, motoneurons, before])]). relacion([sujeto(['Because', serotonin, is, a, relevant, pathophysiological, factor, in, several, neurological, diseases, such, as, bipolar, disorder, and, depression, tools, to, generate, or]), verbo([maintain]), complemento([serotonergic, neurons, might, be, of, therapeutic, value])]). relacion([sujeto(['Culture', systems, for, these, cells, including, embryoid, bodies, based, and, monolayer, differentiation]), verbo([have]), complemento([been, 'established,', which, allows, the, generation, of, up, to, 50, '%', serotonergic, neurons, in, all, neurons, developed])]). relacion([sujeto(['Chemokines', and, their, receptors, are, crucially]), verbo([involved]), complemento([in, the, development, of, atherosclerotic, lesions, by, directing, monocyte, and, 'T', cell, recruitment])]). relacion([sujeto(['The', 'CC-chemokine', receptors, 1, '(', 'CCR1)', and, 5, '(', 'CCR5)']), verbo([expressed]), complemento([on, these, cells, bind, chemokines, implicated, in, 'atherosclerosis,', namely, 'CCL5/RANTES'])]). relacion([sujeto(['Although', general, blockade, of, 'CCL5', receptors, reduces, 'atherosclerosis,', specific, roles, of, 'CCR1', and, 'CCR5']), verbo([have]), complemento([not, been, unequivocally, determined])]). relacion([sujeto(['We']), verbo([provide]), complemento([two, independent, lines, of, investigation, to, dissect, the, effects, of, 'Ccr1', and, 'Ccr5', deletion, in, apolipoprotein, 'E-deficient', '(', 'ApoE-/-)', mice, in, a, collaboration, between, 'Aachen/Germany', and, 'Geneva/Switzerland'])]). relacion([sujeto(['Concordantly,', both, laboratories]), verbo([found]), complemento([that, lesion, formation, was, reduced, in, 'ApoE-/-', 'Ccr5-/-', mice])]). relacion([sujeto(['Conversely,', plaque, 'area,', 'T', 'cell,', and, 'interferon-gamma', content, were]), verbo([increased]), complemento([in, 'ApoE-/-', 'Ccr1-/-', mice])]). relacion([sujeto(['Genetic', deletion, of, 'Ccr5', but, not, 'Ccr1', in, 'ApoE-/-', mice, protects, from, 'diet-induced', 'atherosclerosis,']), verbo([associated]), complemento([with, a, more, stable, plaque, 'phenotype,', reduced, mononuclear, cell, 'infiltration,', 'Th1-type', immune, 'responses,', and, increased, 'interleukin-10', expression])]). relacion([sujeto(['GATA-3', was]), verbo([found]), complemento([in, the, luminal, cells, of, mammary, ducts, and, the, body, cells, of, terminal, end, buds, '(', 'TEBs)'])]). relacion([sujeto(['After', acute, 'GATA-3', 'loss,', adult, mice, exhibited, undifferentiated, luminal, cell, expansion, with, 'basement-membrane', 'detachment,', which]), verbo([led]), complemento([to, 'caspase-mediated', cell, death, in, the, long, term])]). relacion([sujeto(['Further,', 'FOXA1', was, identified, as, a, downstream]), verbo([target]), complemento([of, 'GATA-3', in, the, mammary, gland])]). relacion([sujeto(['This']), verbo([suggests]), complemento([that, 'GATA-3', actively, maintains, luminal, epithelial, differentiation, in, the, adult, mammary, 'gland,', which, raises, important, implications, for, the, pathogenesis, of, breast, cancer])]). relacion([sujeto(['T-box']), verbo([expressed]), complemento([in, 'T', cells, '(', 'T-bet)', and, 'GATA-binding', protein, 3, '(', 'GATA-3)', are, transcriptional, factors, that, play, a, crucial, role, in, 'Th1', and, 'Th2', development])]). relacion([sujeto(['Plasma', 'IL-18', concentration, was]), verbo([increased]), complemento([significantly, in, all, 'SLE', patients, '(', p, &, 'lt;', 0.05, ')'])]). relacion([sujeto(['The', elevated, gene, expressions, of, 'Th1/Th2', transcription, factors, and, cytokines, should]), verbo([provide]), complemento([a, useful, tool, for, assessing, the, functional, status, of, 'T-helper', lymphocytes, in, 'SLE', disease, development])]). relacion([sujeto(['This', essential, epidermal, 'barrier,', composed, of, cornified, proteins, encased, in, 'lipids,']), verbo([prevents]), complemento([both, water, loss, and, entry, of, infectious, or, toxic, substances])]). relacion([sujeto(['We', uncover, that, the, transcription, factor, 'GATA-3', is]), verbo([required]), complemento([to, establish, the, epidermal, barrier, and, survive, in, the, ex, utero, environment])]). relacion([sujeto(['Genomic', analysis, identifies, highly]), verbo([conserved]), complemento(['GATA-3', binding, sites, bound, in, vivo, by, 'GATA-3', in, the, first, intron, of, the, lipid, acyltransferase, gene, 'AGPAT5'])]). relacion([sujeto(['Comparison', of, these, animal, models, illustrates, how, impairment, of, the, skin, barrier, by, two, genetically, distinct, mechanisms]), verbo([leads]), complemento([to, innate, immune, 'responses,', as, observed, in, the, common, human, skin, disorders, psoriasis, and, atopic, dermatitis])]). relacion([sujeto(['The', 'Polycomb', group, '(', 'PcG)', gene, products]), verbo([regulate]), complemento([the, maintenance, of, the, homeobox, gene, expression, in, 'Drosophila', and, vertebrates, and, also, the, cell, cycle, progression, in, thymocytes, and, 'Th2', cell, differentiation, in, mature, 'T', cells])]). relacion([sujeto(['We', herein, studied, the, role, of, 'PcG', gene, 'bmi-1', product, in, 'Th1/Th2', cell, differentiation, and]), verbo([found]), complemento([that, 'Bmi-1', facilitates, 'Th2', cell, differentiation, in, a, 'Ring', 'finger-dependent', manner])]). relacion([sujeto(['Biochemical', studies, indicate, that, 'Bmi-1']), verbo([interacts]), complemento([with, 'GATA3', in, 'T', 'cells,', which, is, dependent, on, the, 'Ring', finger, of, 'Bmi-1'])]). relacion([sujeto(['The', overexpression, of, 'Bmi-1', resulted, in, a]), verbo([decreased]), complemento([ubiquitination, and, an, increased, protein, stability, of, 'GATA3'])]). relacion([sujeto(['In', 'bmi-1-deficient', 'Th', 'cells,', the, levels, of, 'Th2', cell, differentiation]), verbo([decreased]), complemento([as, the, degradation, and, ubiquitination, on, 'GATA3', increased])]). relacion([sujeto(['Therefore,', 'Bmi-1', plays, a, crucial, role, in, the, control, of, 'Th2', cell, differentiation, in, a, 'Ring', 'finger-dependent', manner, by]), verbo([regulating]), complemento(['GATA3', protein, stability])]). relacion([sujeto(['Protein', kinase, 'C', theta, '(', 'PKCtheta)', is, essential, for, 'T', cell, 'activation,', as, it, is]), verbo([required]), complemento([for, the, activation, of, 'NF-kappaB', and, expression, of, 'IL-2'])]). relacion([sujeto(['PKCtheta']), verbo([has]), complemento([also, been, shown, to, affect, 'NFAT', activation, and, 'Th2', differentiation])]). relacion([sujeto(['Overexpression', of, 'GATA3', by, retroviral, infection, in, 'PKCtheta-deficient', 'T', cells, resulted, in]), verbo([increased]), complemento([expansion, of, 'IL-4-producing', 'T', cells, and, higher, 'IL-4', production, than, that, of, wild, type, 'Th2', cells])]). relacion([sujeto(['Our', observations]), verbo([suggest]), complemento([that, 'PKCtheta', regulates, 'Th2', cytokine, expression, via, 'GATA3'])]). relacion([sujeto(['Gata3', and, 'Gata2', are]), verbo([expressed]), complemento([in, the, inner, 'ear,', and, to, gain, more, insight, into, their, roles, in, otic, 'development,', we, made, a, detailed, expression, analysis, in, chicken, embryos])]). relacion([sujeto(['In', contrast, to, 'Gata2,', 'Gata3', was, mainly]), verbo([expressed]), complemento([in, the, developing, sensory, 'epithelia,', reflecting, the, importance, of, this, factor, in, the, 'sensory-neural', development, of, the, inner, ear])]). relacion([sujeto(['While', the, later, expression, patterns, of, both, 'Gata3', and, 'Gata2', were, highly]), verbo([conserved]), complemento([between, chicken, and, 'mouse,', important, differences, were, observed, especially, with, 'Gata3', during, early, otic, 'development,', providing, indications, of, divergent, molecular, control, during, placode, invagination, in, mice, and, chickens])]). relacion([sujeto(['We', also]), verbo([found]), complemento([indications, that, the, regulatory, hierarchy, observed, in, 'mouse,', where, 'Gata3', is, upstream, of, 'Gata2', and, 'Fgf10,', could, be, conserved, in, chicken])]). relacion([sujeto(['We']), verbo([found]), complemento([that, the, action, of, 'TAp63', is, mediated, at, the, molecular, level, by, direct, and, indirect, transactivation, of, 'IKKalpha', and, 'Ets-1,', respectively])]). relacion([sujeto(['We', also]), verbo([found]), complemento([that, 'DeltaNp63', upregulates, 'IKKalpha', 'indirectly,', through, 'GATA-3'])]). relacion([sujeto(['A', multitude, of, breast, cancer, mRNA, profiling, studies]), verbo([has]), complemento([stratified, breast, cancer, and, defined, gene, sets, that, correlate, with, outcome])]). relacion([sujeto(['However,', the, number, of, genes, used, to, predict, patient, outcome, or, define, tumor, subtypes, by, 'RNA', expression, studies, is, 'variable,', 'nonoverlapping,', and, generally]), verbo([requires]), complemento([specialized, technologies, that, are, beyond, those, used, in, the, routine, pathology, laboratory])]). relacion([sujeto(['We']), verbo([have]), complemento([used, 'AQUA-based', objective, quantitative, analysis, of, tissue, microarrays, toward, the, goal, of, discovery, of, a, minimal, number, of, markers, with, maximal, prognostic, or, predictive, value, that, can, be, applied, to, the, conventional, 'formalin-fixed,', 'paraffin-embedded', tissue, section])]). relacion([sujeto(['With', further, 'validation,', this, test]), verbo([has]), complemento([both, the, familiarity, and, specificity, for, widespread, use, in, management, of, breast, cancer])]). relacion([sujeto(['Among', neurogenic, 'factors,', the, neuropeptides]), verbo([have]), complemento([an, important, regulatory, influence, on, immune, system, activity, and, may, lead, to, allergic, sensitization])]). relacion([sujeto(['In', 'contrast,', elevated, levels, of, 'SP', were]), verbo([associated]), complemento([with, reduced, 'GATA3', and, 'SOCS3', expression, and, with, increased, 'IFN-gamma', concentrations])]). relacion([sujeto(['Allergic', sensitization, was, more, prevalent, in, children, with, higher, 'SOM', and, 'VIP', concentrations, but, not]), verbo([associated]), complemento([with, 'SP', levels])]). relacion([sujeto(['Our', data]), verbo([reveal]), complemento([an, association, between, neuropeptides, and, modulatory, effects, on, immune, cells, in, 'vivo,', especially, on, 'Th1/Th2', balance, with, a, correlation, to, allergic, sensitization, in, children])]). relacion([sujeto(['We']), verbo([suggest]), complemento([that, elevated, 'SOM', and, 'VIP', concentrations, and, the, inducing, factors, should, be, considered, as, allergy, risk, factors])]). relacion([sujeto(['Although', invariant, 'NKT', '(', 'iNKT)', cells]), verbo([participate]), complemento([in, many, aspects, of, immune, 'responses,', the, molecular, mechanisms, regulating, their, 'development,', 'maturation,', and, activation, are, still, poorly, understood])]). relacion([sujeto(['GATA-3', is, a, 'T', 'cell-specific', transcription, factor, that, is, also]), verbo([expressed]), complemento([in, iNKT, cells])]). relacion([sujeto(['The', critical, role, of, 'GATA-3', in, conventional, alphabeta, 'T', cells]), verbo([has]), complemento([been, well, 'documented,', but, whether, 'GATA-3', also, regulates, the, development, and, function, of, iNKT, cells, is, unknown])]). relacion([sujeto(['In', the, present, 'study,', we]), verbo([report]), complemento([that, deficiency, of, 'GATA-3', results, in, 'cell-intrinsic', defects, in, the, thymic, development, and, peripheral, maturation, of, murine, iNKT, cells])]). relacion([sujeto(['In', 'addition,', 'GATA-3', is, also]), verbo([required]), complemento([for, 'survival,', 'activation,', and, effector, functions, of, this, unique, population, of, 'T', cells])]). relacion([sujeto(['Our', data, also]), verbo([reveal]), complemento([a, previously, unidentified, peripheral, maturation, step, that, is, 'GATA-3', dependent])]). relacion([sujeto(['Recent', studies]), verbo([have]), complemento([demonstrated, that, members, of, the, 'GATA-binding', protein, '(', 'GATA)', family, '(', 'GATA4', and, 'GATA5)', might, have, pivotal, roles, in, the, transcriptional, upregulation, of, mucin, genes, '(', 'MUC2,', 'MUC3', and, 'MUC4)', in, gastrointestinal, epithelium])]). relacion([sujeto(['The', 'zinc-finger', 'GATA3', transcription, factor]), verbo([has]), complemento([been, reported, to, be, involved, in, the, growth, control, and, differentiation, of, breast, epithelial, cells])]). relacion([sujeto(['We', therefore, designed, the, present, study, to, elucidate, whether, 'MUC1', expression, is]), verbo([regulated]), complemento([by, 'GATA3', in, breast, cancer, cells])]). relacion([sujeto(['We', determined, that, 'GATA3', knockdown, assays]), verbo([led]), complemento([to, a, decrease, in, 'MUC1', protein, expression, in, 'MCF7', and, 'T47D', cells])]). relacion([sujeto(['GATA3', expression, was, also, highly]), verbo([associated]), complemento([with, estrogen, receptor, and, progesterone, receptor, status, '(', p, =, 0.0001, ')', and, tumor, grade, '(', p, =, 0.004, ')', in, breast, carcinomas])]). relacion([sujeto(['Our', study]), verbo([provides]), complemento([evidence, indicating, that, 'GATA3', is, probably, a, mediator, for, the, transcriptional, upregulation, of, 'MUC1', expression, in, some, breast, cancers])]). relacion([sujeto(['Selectin-dependent', cell, adhesion]), verbo([mediates]), complemento([inflammatory, extravasation, and, routine, homing, of, lymphocytes])]). relacion([sujeto(['Most', resting, peripheral, 'T', lymphocytes, lack, expression, of, sialyl, 'Lewis', 'X,', the, carbohydrate, ligand, for, 'selectins,', and, are]), verbo([induced]), complemento([to, strongly, express, it, upon, activation])]). relacion([sujeto(['T', helper, 1, '(', 'Th1)', cells, are, known, to, more, preferentially]), verbo([express]), complemento([sialyl, 'Lewis', 'X', as, compared, with, 'T', helper, 2, '(', 'Th2)', cells, upon, activation])]). relacion([sujeto(['The', molecular, basis, for, this, preferential, 'expression,', 'however,']), verbo([has]), complemento([not, been, elucidated, to, date])]). relacion([sujeto(['Here', we, show, that, the, gene, for, fucosyltransferase, 'VII', '(', 'FUT7),', the, 'rate-limiting', enzyme, for, sialyl, 'Lewis', 'X', 'synthesis,', is, a, unique, example, of, the, human, genes, with]), verbo([binding]), complemento([sites, for, both, 'GATA-3', and, 'T-bet,', two, opposing, factors, for, 'Th1', and, 'Th2', 'development,', and, is, regulated, transcriptionally, by, a, balance, of, the, two, interacting, transcription, factors])]). relacion([sujeto(['T-bet']), verbo([promotes]), complemento([and, 'GATA-3', represses, 'FUT7', transcription])]). relacion([sujeto(['Our', results, indicated, that, 'T-bet', interferes, with, the]), verbo([binding]), complemento([of, 'GATA-3', to, its, target, 'DNA,', and, also, that, 'GATA-3', significantly, interferes, with, the, binding, of, 'T-bet', to, the, 'FUT7', promoter])]). relacion([sujeto(['T-bet']), verbo([has]), complemento([a, binding, ability, to, 'GATA-3,', 'CBP/P300,', and, 'Sp1', to, form, a, transcription, factor, 'complex,', and, 'GATA-3', regulates, 'FUT7', transcription, by, 'phosphorylation-dependently', recruiting, histone, deacetylase, '(', 'HDAC)-3/HDAC-5', and, by, competing, with, 'CBP/P300', in, binding, to, the, 'N', terminus, of, 'T-bet'])]). relacion([sujeto(['These', results, indicate, that, the, 'GATA-3/T-bet', transcription, factor, complex]), verbo([regulates]), complemento([the, 'cell-lineage-specific', expression, of, the, lymphocyte, homing, receptors])]). relacion([sujeto(['SATB1', '(', special, 'AT-rich', sequence]), verbo([binding]), complemento([protein, 1, ')', organizes, cell, 'type-specific', nuclear, architecture, by, anchoring, specialized, 'DNA', sequences, and, recruiting, chromatin, remodeling, factors, to, control, gene, transcription])]). relacion([sujeto(['We', studied, the, role, of, 'SATB1', in]), verbo([regulating]), complemento([the, coordinated, expression, of, 'Il5,', 'Il4', and, 'Il13,', located, in, the, 200, -, kb, 'T-helper', 2, '(', 'T(H)2)', cytokine, locus, on, mouse, chromosome, 11])]). relacion([sujeto(['We', show, that, on, 'T(H)2', cell, 'activation,', 'SATB1', expression, is, rapidly]), verbo([induced]), complemento([to, form, a, unique, transcriptionally, active, chromatin, structure, at, the, cytokine, locus])]). relacion([sujeto(['In', 'addition,', histone, 'H3', is, acetylated, at, 'Lys9', and, 'Lys14,', and, the, 'T(H)2-specific', factors, 'GATA3,', 'STAT6', and, 'c-Maf,', the, 'chromatin-remodeling', enzyme, 'Brg1', and, 'RNA', polymerase, 'II', are, all]), verbo([bound]), complemento([across, the, 200, -, kb, region])]). relacion([sujeto(['Before', 'activation,', the, 'T(H)2', cytokine, locus, is, already]), verbo([associated]), complemento([with, 'GATA3', and, 'STAT6,', showing, some, 'looping,', but, these, are, insufficient, to, induce, cytokine, gene, expression])]). relacion([sujeto(['Using', 'RNA', 'interference,', we, show, that, on, cell, 'activation,', 'SATB1', is]), verbo([required]), complemento([not, only, for, compacting, chromatin, into, dense, loops, at, the, 200, -, kb, cytokine, locus, but, also, for, inducing, 'Il4,', 'Il5,', 'Il13', and, 'c-Maf', expression])]). relacion([sujeto(['In', this, study, we, demonstrated, that, a]), verbo([conserved]), complemento(['YxKxHxxxRP', motif, '(', aa, 345, -, 354, ')', adjacent, to, the, 'C-terminal', zinc, finger, domain, of, 'GATA3', plays, a, critical, in, its, 'DNA', binding, and, 'functions,', including, transcriptional, 'activity,', the, ability, to, induce, chromatin, remodeling, of, the, 'Th2', cytokine, gene, 'loci,', and, 'Th2', cell, differentiation])]). relacion([sujeto(['Thus,', we, identified, a, novel]), verbo([conserved]), complemento(['YxKxHxxxRP', motif, adjacent, to, the, 'C-terminal', zinc, finger, domain, of, 'GATA3', that, is, indispensable, for, 'GATA3', 'DNA', binding, and, functions])]). relacion([sujeto(['Human', 'GATA3', haploinsufficiency]), verbo([leads]), complemento([to, 'HDR', '(', 'hypoparathyroidism,', deafness, and, renal, 'dysplasia)', 'syndrome,', demonstrating, that, the, development, of, a, specific, subset, of, organs, in, which, this, transcription, factor, is, expressed, is, exquisitely, sensitive, to, gene, dosage])]). relacion([sujeto(['These', data, demonstrate, that, a, single, 'distant,', 'tissue-specific', enhancer, can, direct, 'GATA-3', gene, expression, to]), verbo([confer]), complemento([all, embryonic, patterning, information, that, is, required, for, successful, execution, of, 'metanephrogenesis,', and, that, the, dosage, of, 'GATA-3', required, has, a, threshold, between, 50, '%', and, 70, '%', of, diploid, activity])]). relacion([sujeto(['Effects', of, cannabinoids, '(', 'CBs)', are]), verbo([mediated]), complemento([by, two, types, of, 'receptors,', 'CB1', and, 'CB2'])]). relacion([sujeto(['In', this, 'report,', we, investigated, whether, 'CBs']), verbo([regulate]), complemento([gene, expression, of, their, cognate, receptors, in, 'T', cells, and, studied, underlying, mechanisms, in, 'CD4+', 'Jurkat', 'T', cells])]). relacion([sujeto(['Transcription', of, the, 'CB1', gene, was, strongly]), verbo([induced]), complemento([in, response, to, 'Delta9-tetrahydrocannabinol', '(', 'THC),', whereas, the, 'CB2', gene, was, not, regulated])]). relacion([sujeto(['The', induction, of, 'CB1', gene, expression, is]), verbo([mediated]), complemento([by, 'CB2', receptors, 'only,', as, demonstrated, by, using, the, 'CB1', and, 'CB2', agonists, 'R(+)-methanandamide', and, 'JWH', 15, ',', 'respectively,', and, combinations, of, 'THC', plus, 'CB1-', and, 'CB2-specific', antagonists])]). relacion([sujeto(['Induction', of, 'IL-4', mRNA, as, well, as, 'IL-4', protein]), verbo([release]), complemento([from, the, cells, are, necessary, for, the, following, induction, of, the, 'CB1', gene])]). relacion([sujeto(['Transactivation', of, the, 'CB1', gene, in, response, to, 'IL-4', is, then]), verbo([mediated]), complemento([by, the, transcription, factor, 'STAT6,', as, shown, by, using, decoy, oligonucleotides, against, 'STAT6'])]). relacion([sujeto(['An']), verbo([increase]), complemento([in, 'CB1-mediated', phosphorylation, of, 'MAPK', in, cells, prestimulated, with, 'CB2-specific', agonists, suggests, 'up-regulation', of, functional, 'CB1', receptor, proteins])]). relacion([sujeto(['In', 'summary,', 'up-regulation', of, 'CB1', in, 'T', lymphocytes, in, response, to, 'CBs', themselves, may, facilitate, or]), verbo([enhance]), complemento([the, various, immunomodulatory, effects, related, to, 'CBs'])]). relacion([sujeto(['Obesity', is, characterized, by, an]), verbo([increase]), complemento([in, adipose, tissue, mass, resulting, from, enlargement, of, existing, fat, cells, '(', 'hypertrophy)', 'and/or', from, increased, number, of, adipocytes, '(', 'hyperplasia)'])]). relacion([sujeto(['The', inability, of, the, adipose, tissue, to]), verbo([recruit]), complemento([new, fat, cells, may, cause, ectopic, fat, deposition, and, insulin, resistance])]). relacion([sujeto(['We', examined, the, expression, of, candidate, genes]), verbo([involved]), complemento([in, adipocyte, proliferation, 'and/or', differentiation, '[', 'CCAAT/enhancer-binding', protein, '(', 'C/EBP)', 'alpha,', 'C/EBPdelta,', 'GATA', 'domain-binding', protein, 3, '(', 'GATA3),', 'C/EBPbeta,', peroxisome, 'proliferator-activated', receptor, '(', 'PPAR)', 'gamma2,', signal, transducer, and, activator, of, transcription, 5, 'A', '(', 'STAT5A),', 'Wnt-10b,', tumor, necrosis, factor, 'alpha,', sterol, regulatory, 'element-binding', protein, 1, c, '(', 'SREBP1c),', 11, 'beta-hydroxysteroid', 'dehydrogenase,', 'PPARG', 'angiopoietin-related', protein, '(', 'PGAR),', 'insulin-like', growth, factor, 1, ',', 'PPARgamma', coactivator, 1, 'alpha,', 'PPARgamma', coactivator, 1, 'beta,', and, 'PPARdelta]', in, subcutaneous, adipose, tissue, from, 42, obese, individuals, with, type, 2, diabetes, and, 25, 'non-diabetic', subjects, matched, for, age, and, obesity])]). relacion([sujeto(['This', 'cross-sectional', study, supports, the, hypothesis, that, impaired, expression, of, adipogenic, genes, may, result, in, impaired, 'adipogenesis,', potentially]), verbo([leading]), complemento([to, larger, fat, cells, in, subcutaneous, adipose, tissue, and, insulin, resistance])]). relacion([sujeto(['To', overcome, this, 'limitation,', we]), verbo([have]), complemento([used, the, microarray, technology, to, study, 56, samples, of, invasive, ductal, carcinoma])]). relacion([sujeto(['We', infer, a, robust, and, reliable, signature, of, 10, 'genes,', which, is]), verbo([associated]), complemento([with, 'ER', expression, and, presumably, therapeutically, relevant, biological, processes])]). relacion([sujeto(['We']), verbo([have]), complemento([recently, demonstrated, that, peripheral, blood, 'NK', cells, biased, for, secreting, 'IL-5', '(', 'NK2', 'bias)', are, associated, with, the, remission, state, of, 'MS'])]). relacion([sujeto(['In', this, 'study,', we]), verbo([report]), complemento([that, 'MS', patients, in, remission, differentially, express, 'CD11c', on, 'NK', cell, surface, '(', operationally, defined, as, 'CD11chigh', or, 'CD11clow)'])]). relacion([sujeto(['Given', previous, evidence, showing, an, association, between, an]), verbo([increased]), complemento([level, of, proinflammatory, cytokines, and, temporal, disease, activity, in, 'MS,', we, postulate, that, inflammatory, signals, may, play, a, role, in, inducing, the, 'CD11chigh', 'NK', cell, phenotype])]). relacion([sujeto(['As', 'such,', a, higher, expression, of, 'CD11c', on, 'NK', cells, may, reflect, the, temporal, activity, of, 'MS', as, well, as, a]), verbo([loss]), complemento([of, regulatory, 'NK2', 'phenotype,', which, may, allow, us, to, use, it, as, a, potential, biomarker, to, monitor, the, immunological, status, of, 'MS', patients])]). relacion([sujeto(['Those', characteristics, are, reminiscent, of, human, 'CD56(hi)', 'CD16-', 'NK', 'cells,', which, we]), verbo([found]), complemento([expressed, 'CD127', and, had, more, 'GATA-3', expression, than, human, 'CD56+', 'CD16+', 'NK', cells])]). relacion([sujeto(['The', basic, 'helix-loop-helix', transcription, factor, 'Hand2,', together, with, 'Ascl1,', 'Phox2a,', 'Phox2b', and, 'Gata2/Gata3,', is]), verbo([induced]), complemento([by, bone, morphogenetic, proteins, in, neural, 'crest-derived', precursor, cells, during, sympathetic, neuron, generation])]). relacion([sujeto(['Using', the, zebrafish, hand2, deletion, mutant, hands, 'off,', we]), verbo([have]), complemento([now, investigated, the, physiological, role, of, hand2, in, the, development, of, sympathetic, ganglia])]). relacion([sujeto(['The', ecotropic, viral, integration, site, 1, '(', 'EVI1)', gene, was, identified, as, a, common, locus, of, retroviral, integration, in, myeloid, tumors]), verbo([found]), complemento([in, mice])]). relacion([sujeto(['EVI1', gene, is, highly]), verbo([conserved]), complemento([through, evolution, and, human, gene, 'EVI1', on, chromosome, 3, q26, encodes, zinc, 'fingers-containing', transcription, factor])]). relacion([sujeto(['EVI1', is]), verbo([expressed]), complemento([in, nonhematopoietic, tissues, but, not, in, normal, blood, or, bone, marrow])]). relacion([sujeto(['EVI1', was, detected, in, hematopoietic, cells, in, 'retrovirus-induced', myeloid, leukemias, in, mice, and, several]), verbo([reports]), complemento([documented, 'EVI1', expression, in, human, myelodysplastic, syndromes, and, other, hematologic, malignancies, without, 3, q26, translocations])]). relacion([sujeto(['EVI1', is, abnormally]), verbo([expressed]), complemento([in, human, myeloid, leukemias, that, are, associated, with, the, 't(3;3)(q21;q26),', 't(3;21)(q26;q22),', 'inv(3)(q21q26)', and, other, chromosomal, rearrangements])]). relacion([sujeto(['EVI1', is, a, transcriptional, repressor, which]), verbo([inhibits]), complemento([transforming, growth, factor, beta, '(', 'TGFbeta)', family, signalling, by, binding, signal, transducers, '(', 'Smad', 'proteins)', and, recruiting, transcriptional, corepressors])]). relacion([sujeto(['EVI1']), verbo([inhibits]), complemento(['TGFbeta-mediated', apoptosis])]). relacion([sujeto(['Knockdown', of, 'EVI1', function, by, small, interference, 'RNA']), verbo([increases]), complemento([the, sensitivity, of, malignant, cells, to, 'TGFbeta-mediated', or, other, 'inducer-mediated', apoptosis])]). relacion([sujeto(['EVI1', functions, in, some, cases, as, a, transcriptional, activator, which]), verbo([stimulates]), complemento([for, example, 'GATA2', and, 'GATA3', promoters])]). relacion([sujeto(['The', study, of, 'EVI1']), verbo([target]), complemento([genes, will, help, to, clear, the, mechanism, by, which, 'EVI1', upregulates, cell, 'proliferation,', impairs, cell, 'differentiation,', and, induces, cell, transformation])]). relacion([sujeto(['Haploinsufficiency', of, the, zinc, finger, transcription, factor, 'GATA3']), verbo([causes]), complemento([the, triad, of, 'hypoparathyroidism,', deafness, and, renal, 'dysplasia,', known, by, its, acronym, 'HDR', syndrome])]). relacion([sujeto(['Hearing']), verbo([loss]), complemento([in, 'HDR', syndrome, is, moderate, to, 'severe,', seems, to, be, slightly, worse, at, the, higher, end, of, the, frequency, spectrum, and, may, be, progressive, with, age])]). relacion([sujeto(['The', absence, of, otoacoustic, emissions, and, the]), verbo([loss]), complemento([of, frequency, selectivity, suggest, an, important, role, for, outer, hair, cells, in, causing, the, hearing, loss])]). relacion([sujeto(['We', wanted, to, identify, the, critical, intracellular, signaling, molecules, in, 'T', cells, that]), verbo([induce]), complemento([atopic, 'dermatitis-like', skin, legions, in, 'NC/Nga', mice])]). relacion([sujeto(['We', examined, the, levels, of, signal, transduction, and, cytokine, production, in, 'T', 'cells,', particularly, those, in, atopic, 'dermatitis-like', lesions]), verbo([induced]), complemento([by, the, topical, injection, of, mite, antigens, in, 'NC/Nga', mice, under, specific, 'pathogen-free', conditions])]). relacion([sujeto(['In', 'NC/Nga', mice]), verbo([maintained]), complemento([under, specific, 'pathogen-free', 'conditions,', the, capability, of, 'T(H)1/T(H)2', and, 'T', cytotoxic, 1, /, 'T', cytotoxic, 2, '(', 'Tc1/Tc2)', cell, differentiation, increased, significantly])]). relacion([sujeto(['T-cell', antigen, 'receptor-mediated', activation, of, the, extracellular, 'signal-regulated', 'kinase/mitogen-activated', protein, kinase, cascade, and]), verbo([nuclear]), complemento(['factor-kappaB', '(', 'NF-kappaB)', signaling, were, enhanced, in, 'NC/Nga', 'T', cells])]). relacion([sujeto(['The', expression, of, 'T(H)2', cytokines, '(', 'IL-4,', 'IL-13,', and, 'IL-5)', and, that, of, 'GATA-binding', protein, 3, '(', 'GATA3),', avian, musculoaponeurotic, fibrosarcoma, '(', 'c-Maf),', 'NF-kappaB,', and, activator, protein, 1, '(', 'AP1)', selectively]), verbo([increased]), complemento([in, draining, lymph, node, 'T', cells, of, 'NC/Nga', mice])]). relacion([sujeto(['Hyperresponsive', 'T(H)2', cells, with, an]), verbo([enhanced]), complemento([activity, of, 'NF-kappaB', and, 'AP1', play, a, crucial, role, in, the, pathogenesis, of, atopic, 'dermatitis-like', skin, lesions, in, 'NC/Nga', mice])]). relacion([sujeto(['In', 'Gata3-null', 'embryos,', there, was, significant, impairment, of, 'SA', differentiation, and]), verbo([increased]), complemento([apoptosis, in, adrenal, chromaffin, cells, and, sympathetic, neurons])]). relacion([sujeto(['These', data, not, only, underscore, the, hypothesis, that, 'Gata3', is, essential, for, the, differentiation, and, survival, of, 'SA', 'cells,', but, also]), verbo([suggest]), complemento([that, their, differentiation, is, controlled, by, mutually, reinforcing, feedback, transcriptional, interactions, between, 'Gata3,', 'Mash1,', 'Hand2', and, 'Phox2b', in, the, 'SA', lineage])]). relacion([sujeto(['The', critical, role, of, 'IL-5', '(', 'interleukin-5)', in, eosinophilic, inflammation, implicates, it, as, a, therapeutic]), verbo([target]), complemento([for, allergic, diseases])]). relacion([sujeto(['We']), verbo([provide]), complemento([evidence, that, 'HDAC4', '(', histone, deacetylase, 4, ')', and, 'p300,', a, known, 'HAT', '(', histone, 'acetyltransferase),', reversibly, controlled, the, activity, of, the, 'IL-5', promoter, in, vivo, and, in, 'vitro,', with, a, concurrent, alteration, of, histone, 'H3', acetylation, status, at, the, promoter, regions])]). relacion([sujeto(['Point', mutation, and, reporter, 'ChIP', '(', chromatin, 'immunoprecipitation)', studies, determined, that, the, four, transcription, factors]), verbo([binding]), complemento([on, the, 'IL-5', 'promoter,', i])]). relacion([sujeto(['C/EBPbeta', '(', 'CAAT/enhancer-binding', protein, 'beta),', 'GATA3', '(', 'GATA']), verbo([binding]), complemento([protein, 3, ')', ',', 'NFAT', '(', nuclear, factor, of, activated, 'T', 'cells)', and, 'YY1', '(', 'Yin', and, 'Yang', 1, ')', ',', were, essential, for, the, recruitment, of, 'HDAC4'])]). relacion([sujeto(['Consistent', with, these, 'observations,', 'HDAC4', was]), verbo([found]), complemento([to, form, protein, complexes, with, 'GATA3', and, 'YY1,', and, to, 'co-exist', in, the, nuclei, with, 'GATA3'])]). relacion([sujeto(['We', propose, that, the, unique, regulatory, mechanism, of, 'IL-5', gene, transcription]), verbo([involves]), complemento([the, reversible, histone, modification, catalysed, by, 'HDAC4', and, 'p300,', which, are, recruited, by, the, transcription, factors])]). relacion([sujeto(['Familial', hypoparathyroidism, may, be]), verbo([caused]), complemento([by, mutations, of, several, genes])]). relacion([sujeto(['We', identified, three, novel, mutations, in, the, 'GATA3', gene, responsible, for, familial, hypoparathyroidism, and, 'deafness:', 1, ')', a, frameshift, deletion, occurring, in, codon, 160, '(', 478, 'delG)', was, hypothesized, to, disrupt, dual, zinc, fingers, as, well, as, one, transactivating, 'domain;', 2, ')', a, donor, splice, site, mutation, at, exon, 4, /, intron, 4, boundary, '(', 'IVS4', +, 2, 'T', to, 'GCTTACTTCCC)', was, predicted, to]), verbo([lead]), complemento([to, truncated, 'GATA3', proteins, that, lack, both, 'N-', and, 'C-terminal', 'zinc-containing', 'fingers;', and, 3, ')', a, missense, mutation, 'R353S', was, predicted, to, disrupt, the, helical, turn, and, thus, changed, the, angle, between, the, 'C-terminal', zinc, finger, and, the, adjacent, 'C-terminal', tail])]). relacion([sujeto(['Except', for, a, previously, described, 'polymorphism,', 'G990R,', we, did, not]), verbo([find]), complemento([any, genetic, variants, in, the, 'CaSR', gene])]). relacion([sujeto(['Our', results, expand, the, spectrum, of, mutations, and]), verbo([report]), complemento([the, first, splice, donor, site, mutation, of, the, 'GATA3', gene])]). relacion([sujeto(['In', 'contrast,', we, do, not]), verbo([find]), complemento([causal, sequence, variants, of, the, 'CaSR', gene, from, our, collection, of, familial, hypoparathyroidism])]). relacion([sujeto(['Erythropoiesis', is]), verbo([maintained]), complemento([by, the, hormone, erythropoietin, '(', 'Epo)', binding, to, its, cognate, receptor, '(', 'EpoR)', on, erythroid, progenitor, cells])]). relacion([sujeto(['The', 'Epo-EpoR', interaction, initiates, a, signal, transduction, process, that]), verbo([regulates]), complemento([the, 'survival,', growth, and, differentiation, of, these, cells])]). relacion([sujeto(['Originally', perceived, as, highly, 'lineage-restricted,', 'Epo', is, now, recognised, to]), verbo([have]), complemento([pleiotropic, effects, extending, beyond, the, maintenance, of, red, cell, mass])]). relacion([sujeto(['Functional', interactions, between, 'Epo', and, 'EpoR']), verbo([have]), complemento([been, demonstrated, in, numerous, cells, and, tissues])]). relacion([sujeto(['EpoR', expression, on, neoplastic, cells]), verbo([leads]), complemento([to, concern, that, recombinant, human, 'erythropoietin,', used, to, treat, anaemia, in, cancer, 'patients,', may, augment, tumour, growth])]). relacion([sujeto(['Here', we, demonstrate, that, 'EPO,', at, pharmacological, 'concentrations,', can]), verbo([activate]), complemento([three, major, signalling, 'cascades,', viz])]). relacion([sujeto(['EpoR', synthesis, is, normally, under, the, control, of, 'GATA-1,', but, 'NSCLC', cells, exhibit]), verbo([decreased]), complemento(['GATA-1', levels, compared, to, 'GATA-2,', -, 3, and, -, 6, ',', suggesting, that, 'GATA-1', is, not, essential, for, 'EpoR', production])]). relacion([sujeto(['The']), verbo([increased]), complemento(['Epo-induced', signalling, was, not, associated, with, a, growth, advantage, for, the, 'NSCLC', cells])]). relacion([sujeto(['To']), verbo([gain]), complemento([insight, into, the, molecular, setup, of, the, head, 'mesoderm,', its, similarity, or, dissimilarity, to, the, somitic, 'mesoderm,', and, the, implications, of, its, setup, for, the, progress, of, muscle, 'formation,', we, investigated, the, expression, of, markers, '(', 1, ')', for, mesoderm, segmentation, and, boundary, 'formation,', '(', 2, ')', for, regional, specification, and, somitogenesis, and, '(', 3, ')', for, the, positive, and, negative, control, of, myogenic, differentiation])]). relacion([sujeto(['Importantly,', the, head, mesoderm, lacks, the, transcription, factors, driving, muscle, differentiation, while, genes]), verbo([suppressing]), complemento([differentiation, and, promoting, cell, proliferation, are, expressed])]). relacion([sujeto(['Interestingly,', in, 'GATA-3-/-', 'mice,', noradrenaline, '(', 'NA)', deficiency, is, a, proximal]), verbo([cause]), complemento([of, embryonic, lethality])]). relacion([sujeto(['However,', neither, the, role, of, 'GATA-3', nor, its]), verbo([target]), complemento(['gene(s)', in, the, nervous, system, were, known])]). relacion([sujeto(['Here,', we]), verbo([report]), complemento([that, forced, expression, of, 'GATA-3', resulted, in, an, increased, number, of, tyrosine, hydroxylase, '(', 'TH)', expressing, neurons, in, primary, neural, crest, stem, cell, '(', 'NCSC)', culture])]). relacion([sujeto(['We', also]), verbo([found]), complemento([that, 'GATA-3', transactivates, the, promoter, function, of, 'TH', via, specific, upstream, 'sequences,', a, domain, of, the, 'TH', promoter, residing, at, -, 61, to, -, 39, bp])]). relacion([sujeto(['Surprisingly,', this, domain, does, not, contain, 'GATA-3']), verbo([binding]), complemento([sites, but, possesses, a, binding, 'motif,', a, cAMP, response, element, '(', 'CRE),', for, the, transcription, 'factor,', 'CREB'])]). relacion([sujeto(['In', 'addition,', we]), verbo([found]), complemento([that, 'site-directed', mutation, of, this, 'CRE', almost, completely, abolished, transactivation, of, the, 'TH', promoter, by, 'GATA-3'])]). relacion([sujeto(['Furthermore,', 'protein-protein', interaction, assays, showed, that, 'GATA-3', is, able, to, physically]), verbo([interact]), complemento([with, 'CREB', in, vitro, as, well, as, in, vivo])]). relacion([sujeto(['Based', on, these, 'results,', we, propose, that, 'GATA-3', may]), verbo([regulate]), complemento(['TH', gene, transcription, via, a, novel, and, distinct, 'protein-protein', 'interaction,', and, directly, contributes, to, 'NA', phenotype, specification])]). relacion([sujeto(['We']), verbo([found]), complemento([that, removal, of, the, acetylation, sites, in, 'GATA-1', does, not, impair, its, nuclear, 'localization,', 'steady-state', protein, 'levels,', or, its, ability, to, bind, naked, 'GATA', elements, in, vitro])]). relacion([sujeto(['However,', chromatin, immunoprecipitation, '(', 'ChIP)', experiments, revealed, that, mutant, 'GATA-1', was, dramatically, impaired, in]), verbo([binding]), complemento([to, all, examined, cellular, target, sites, in, 'vivo,', including, genes, that, are, normally, activated, and, repressed, by, 'GATA-1'])]). relacion([sujeto(['Together,', these, results]), verbo([suggest]), complemento([that, acetylation, regulates, chromatin, occupancy, of, 'GATA-1'])]). relacion([sujeto(['These', findings, point, to, a, novel, function, for, transcription, factor, 'acetylation,', perhaps, by, facilitating, protein, interactions]), verbo([required]), complemento([for, stable, association, with, chromatin, templates, in, vivo])]). relacion([sujeto(['Th2', 'differentiation,', which, is, critical, for, allergic, airway, 'disease,', is]), verbo([triggered]), complemento([by, signals, of, the, 'T-cell', receptor, '(', 'TCR)', and, the, cytokines, generated, during, 'polarization,', particularly, 'IL-4'])]). relacion([sujeto(['We']), verbo([report]), complemento([using, 'p62-/-', mice, and, cells, that, p62, acts, downstream, 'TCR', 'activation,', and, is, important, for, 'Th2', polarization, and, 'asthma,', playing, a, significant, role, in, the, control, of, the, sustained, activation, of, 'NF-kappaB', and, late, synthesis, of, 'GATA3', and, 'IL-4', by, participating, in, the, activation, of, the, 'IKK', complex])]). relacion([sujeto(['Peripheral', blood, mononuclear, cells, were]), verbo([stimulated]), complemento([with, 'HBcAg', or, 'HBsAg', to, evaluate, their, potential, to, commit, to, 'TH1', and, 'TH2', differentiation])]). relacion([sujeto(['Although', populations, of, 'CD4+CD25highCTLA-4+', 'T', cells, were, not, different, between, the, patients, and, healthy, 'subjects,', 'IL-10', secreting, cells, were]), verbo([found]), complemento([in, 'CD4+', cells, and, 'CD4+CD25+', cells, in, the, patients, in, response, to, 'HBcAg,', and, they, were, not, found, in, cells, which, were, stimulated, with, 'HBsAg'])]). relacion([sujeto(['Deletion', of, 'CD4+CD25+', 'T', cells]), verbo([increased]), complemento([the, amount, of, 'HBcAg-specific', 'TH1', antibody, when, compared, with, lymphocytes, reconstituted, using, regulatory, 'T', cells, '(', 'P', &, 'lt;', 0.01, ',', 0.03, '%', +, /, -, 0.02, '%', vs, 0.18, '%', +, /, -, 0.05, '%', ')'])]). relacion([sujeto(['The', results, indicate, that, the, mechanism, of, 'T', cell, hyporesponsiveness, to, 'HBcAg', includes, activation, of, 'HBcAg-induced', regulatory, 'T', cells, in, contrast, to, an]), verbo([increase]), complemento([in, 'TH2-committed', cells, in, response, to, 'HBsAg'])]). relacion([sujeto(['To', study, the, effect, of, bifidobacterium, genomic, 'DNA', on, umbilical, cord, blood, mononuclear, cell, '(', 'CBMC),', and, investigate, the, immunoregulation, of, bifidobacterium, 'DNA', and, explore, possible, mechanisms, by, which, bifidobacterium]), verbo([acts]), complemento([against, allergic, reaction])]). relacion([sujeto(['These', cells, were, divided, into, four, 'groups,', control, 'group:', without, any, 'stimulant;', bDNA, 'group:']), verbo([stimulated]), complemento([with, 25, 'microg/ml', 'bDNA;', 'd-bDNA', 'group:', stimulated, with, 25, 'microg/ml', 'd-bDNA;', hDNA, 'group:', stimulated, with, 25, 'microg/ml', hDNA])]). relacion([sujeto(['The', cells, were]), verbo([stimulated]), complemento([with, different, stimulants, in, 'vitro,', at, the, end, of, incubation, culture, supernatant, and, cells, were, collected])]). relacion([sujeto(['After', bDNA, 'stimulation,']), verbo([nuclear]), complemento([factor, 'T-box', expressed, in, 'T', cells, '(', 'T-bet)', mRNA, expression, was, conspicuously, enhanced, as, compared, to, the, other, three, groups, '(', 'P', &, 'lt;', 0.05, ')'])]). relacion([sujeto([bDNA, could]), verbo([promote]), complemento([secretion, of, 'Th1', type, cytokine, 'IL-12,', while, 'Th2', type, cytokine, 'IL-10', level, of, cell, supernatant, was, decreased])]). relacion([sujeto([bDNA, could]), verbo([stimulate]), complemento([secretion, of, 'IFN-gamma', by, 'CBMC', and, inhibit, secretion, of, 'IL-4'])]). relacion([sujeto(['T-bet', mRNA, expression, was, highly]), verbo([enhanced]), complemento([after, bDNA, stimulation])]). relacion([sujeto([bDNA, could, upregulate, 'Th1', type, 'response,', which, may, be, one, of, important, mechanisms, by, which, bifidobacterium]), verbo([inhibit]), complemento([allergic, response])]). relacion([sujeto(['Identification', of, the, mechanisms]), verbo([leading]), complemento([to, malignant, transformation, of, respiratory, cells, may, prove, useful, in, the, prevention, and, treatment, of, 'tobacco-related', lung, cancer])]). relacion([sujeto(['Nitrosamines', 4, -, '(', 'methylnitrosamino)-1-(3-pyridyl)-1-butanone', '(', 'NNK)', and, 'N\'-nitrosonornicotine', '(', 'NNN)', can]), verbo([induce]), complemento([tumors, both, locally, and, systemically])]). relacion([sujeto(['In', addition, to, the, genotoxic, 'effect,', they]), verbo([have]), complemento([been, shown, to, affect, lung, cells, due, to, ligating, the, nicotinic, acetylcholine, receptors, '(', 'nAChRs)', expressed, on, the, plasma, membrane])]). relacion([sujeto(['In', this, 'study,', we, sought, to, establish, the, role, for, nAChRs, in, malignant, transformation]), verbo([caused]), complemento([by, 'NNK', and, 'NNN'])]). relacion([sujeto(['We']), verbo([found]), complemento([that, these, cells, express, 'alpha1,', 'alpha3,', 'alpha5,', 'alpha7,', 'alpha9,', 'alpha10,', 'beta1,', 'beta2,', and, beta4, nAChR, subunits, that, can, form, 'high-affinity', binding, sites, for, 'NNK', and, 'NNN'])]). relacion([sujeto(['Exposure', of, 'BEP2D', cells, to, either, 'NNK', or, 'NNN', in, both, cases]), verbo([increased]), complemento([their, proliferative, potential, which, could, be, abolished, in, the, presence, of, nAChR, antagonists, 'alpha-bungarotoxin,', which, worked, most, effectively, against, 'NNK,', or, 'mecamylamine,', which, was, most, efficient, against, 'NNN'])]). relacion([sujeto(['The', 'BEP2D', cells]), verbo([stimulated]), complemento([with, the, nitrosamines, showed, multifold, increases, of, the, transcription, of, the, 'PCNA', and, 'Bcl-2', genes, by, both, 'real-time', polymerase, chain, reaction, and, 'in-cell', western, assays])]). relacion([sujeto(['To']), verbo([gain]), complemento([a, mechanistic, insight, into, 'NNK-', and, 'NNN-initiated', 'signaling,', we, investigated, the, expression, of, genes, encoding, the, signal, transduction, effectors, 'GATA-3,', nuclear, 'factor-kappaB,', and, 'STAT-1'])]). relacion([sujeto(['Experimental', results, indicated, that, stimulation, of, nAChRs, with, 'NNK']), verbo([led]), complemento([to, activation, of, all, three, signal, transduction, effectors, under, 'consideration,', whereas, 'NNN', predominantly, activated, 'GATA-3', and, 'STAT-1'])]). relacion([sujeto(['The', 'GATA-3', 'protein-binding', activity]), verbo([induced]), complemento([by, 'NNK', and, 'NNN', correlated, with, elevated, gene, expression])]). relacion([sujeto(['The', obtained, results, support, the, novel, concept, of, 'receptor-mediated', action, of, 'NNK', and, 'NNN', placing, cellular, nAChRs, in, the, center, of, the, pathophysiologic, 'loop,', and]), verbo([suggest]), complemento([that, an, nAChR, antagonist, may, serve, as, a, chemopreventive, agent])]). relacion([sujeto(['Here,', we]), verbo([report]), complemento([that, 'L'])]). relacion([sujeto(['Opsonization', with, normal, human, serum]), verbo([enhanced]), complemento([the, infectivity, of, amastigotes, and, promastigotes, only, marginally])]). relacion([sujeto(['Infection', with, amastigotes, was, accompanied, by, 'DC', 'maturation,', as, was, evident, from, the, 'up-regulation', of, 'maturation-associated', 'cell-surface', 'markers,', the]), verbo([nuclear]), complemento([translocation, of, 'RelB,', and, the, release, of, cytokines])]). relacion([sujeto(['When', 'cocultured,', 'amastigote-infected', 'DCs']), verbo([induced]), complemento(['T', helper, cell, type, 1, '(', 'Th1)', responses, both, in, naive, allogeneic, 'CD4(+)', 'T', cells, and, in, autologous, 'CD4(+)', 'T', cells, from, patients, with, 'kala-azar', and, 'up-regulated', the, expression, of, 'T-bet'])]). relacion([sujeto(['Our', data]), verbo([reveal]), complemento([that, infection, with, 'L'])]). relacion([sujeto([donovani, amastigotes]), verbo([induces]), complemento([a, 'Th1', cytokine, milieu, in, both, 'DCs', and, 'T', cells])]). relacion([sujeto(['The', engagement, of, 'CD137', '(', 4, -, 1, 'BB),', an, inducible, 'T', cell, costimulatory, receptor, and, member, of, the, 'TNF', receptor, 'superfamily,', by, agonistic, 'Abs', can]), verbo([promote]), complemento([strong, tumor, and, viral, immunity, mediated, by, 'CD8(+)', 'T', cells, and, stimulate, 'IFN-gamma', production])]). relacion([sujeto(['However,', its, role, in, 'Th2-mediated', immune, responses]), verbo([has]), complemento([not, been, well, defined])]). relacion([sujeto(['Interestingly,', treatment, of, 'C57BL/6', mice, with, agonistic, 'anti-CD137', '(', 2, 'A)', during, sensitization, completely]), verbo([prevents]), complemento([allergic, airway, 'inflammation,', as, shown, by, a, clear, inhibition, of, 'T', cell, and, eosinophil, infiltration, into, the, lung, tissue, and, 'airways,', accompanied, by, diminished, 'Th2', cytokine, production, and, reduced, serum, 'IgE', 'levels,', as, well, as, a, reduction, of, airway, hyperresponsiveness])]). relacion([sujeto(['Our', study]), verbo([has]), complemento([identified, a, novel, pathway, to, inhibit, 'Th2', responses, in, a, 'CD137-dependent', fashion])]). relacion([sujeto(['Recent', studies]), verbo([have]), complemento([demonstrated, that, 'Th2', 'cytokines,', such, as, 'interleukin-4', and, 'interleukin-13,', enhance, fibrotic, processes, by, activating, fibroblast, proliferation, and, collagen, 'production,', whereas, 'interferon-gamma,', a, 'Th1', 'cytokine,', inhibits, these, processes])]). relacion([sujeto(['The', survival, rate, after, bleomycin, was, significantly]), verbo([decreased]), complemento([in, 'GATA-3-tg', mice, compared, with, 'wild-type', mice])]). relacion([sujeto(['Lung', 'interferon-gamma', concentration, was, significantly]), verbo([decreased]), complemento([in, 'GATA-3-tg', mice, compared, with, 'wild-type', mice, by, 7, days, after, either, saline, or, bleomycin, treatment])]). relacion([sujeto(['Exogenous', administration, of, 'interferon-gamma', to, 'GATA-3-tg', mice, improved, the, degree, of, pulmonary, fibrosis, and, thus]), verbo([increased]), complemento([survival])]). relacion([sujeto(['These', results, indicate, that, overexpression, of, 'GATA-3']), verbo([enhances]), complemento([the, development, of, pulmonary, 'fibrosis,', possibly, by, reducing, 'interferon-gamma', levels, in, the, lung])]). relacion([sujeto(['Inner', ear, develops, from, an]), verbo([induced]), complemento([surface, ectoderm, placode, that, invaginates, and, closes, to, form, the, otic, 'vesicle,', which, then, undergoes, a, complex, morphogenetic, process, to, form, the, membranous, labyrinth])]). relacion([sujeto(['Inner', ear, morphogenesis, is, severely, affected, in, 'Gata3', deficient, mouse, 'embryos,', but, the, onset, and, basis, of, the, phenotype]), verbo([has]), complemento([not, been, known])]). relacion([sujeto(['We', show, here, that, 'Gata3', deficiency]), verbo([leads]), complemento([to, severe, and, unique, abnormalities, during, otic, placode, invagination])]). relacion([sujeto(['The', expression, of, several, cell, adhesion]), verbo([mediating]), complemento([genes, is, altered, in, 'Gata3', deficient, ears, suggesting, that, 'Gata3', controls, adhesion, and, morphogenetic, movements, in, early, otic, epithelium])]). relacion([sujeto(['Inactivation', of, 'Gata3']), verbo([leads]), complemento([also, to, a, loss, of, 'Fgf10', expression, in, otic, epithelium, and, auditory, ganglion, demonstrating, that, 'Gata3', is, an, important, regulator, of, 'Fgf-signalling', during, otic, development])]). relacion([sujeto(['The', generalized, 'T-cell', activation, characterizing, 'HIV-1', and, 'SIVmac', infections, in, humans, and, macaques, '(', 'MACs)', is, not]), verbo([found]), complemento([in, the, 'non-pathogenic', 'SIVagm', infection, in, 'African', green, monkeys, '(', 'AGMs)'])]). relacion([sujeto(['We']), verbo([have]), complemento([previously, shown, that, 'TGF-beta1,', 'Foxp3', and, 'IL-10', are, induced, very, early, after, 'SIVagm', infection])]). relacion([sujeto(['We', raised, the, hypothesis, that, 'MACs', are, unable, to]), verbo([respond]), complemento([to, 'TGF-beta1', and, thus, cannot, resorb, 'virus-driven', inflammation])]). relacion([sujeto(['We', therefore, compared, the, very, early, expression, dynamics, of, 'pro-', and, 'anti-inflammatory', markers, as, well, as, of, factors]), verbo([involved]), complemento([in, the, 'TGF-beta1', signaling, pathway, in, 'SIV-infected', 'AGMs', and, 'MACs'])]). relacion([sujeto([')', ',', a, cellular, mediator]), verbo([inhibiting]), complemento([the, 'TGF-beta1', signaling, 'cascade,', characterized, 'SIV-infected', 'MACs'])]). relacion([sujeto(['In', 'AGMs,', we]), verbo([found]), complemento([increases, of, 'gata-3', but, not, 't-bet,', a, longer, lasting, 'up-regulation', of, smad4, '(', days, 1, -, 21, p])]). relacion([sujeto(['i),', a, mediator]), verbo([enhancing]), complemento(['TGF-beta1', 'signaling,', and, no, smad7, 'up-regulations'])]). relacion([sujeto(['Our', data]), verbo([suggest]), complemento([that, the, inability, to, resorb, 'virus-driven', inflammation, and, activation, during, the, pathogenic, 'HIV-1/SIVmac', infections, is, associated, with, an, unresponsiveness, to, 'TGF-beta1'])]). relacion([sujeto(['Steatohepatitis']), verbo([enhances]), complemento([the, severity, of, liver, injury, caused, by, acute, inflammation])]). relacion([sujeto(['CDD', also]), verbo([enhanced]), complemento(['ConA-induced', 'STAT4', 'activation,', but, not, 'STAT6'])]). relacion([sujeto(['T-bet,', regulator, of, the, 'Th1', 'response,', was, 'up-regulated', in, 'CDD-fed', 'mice,', whereas, 'Th2', regulator, 'GATA-3', was, significantly]), verbo([suppressed]), complemento([in, 'CDD-fed', mice, after, 'ConA'])]). relacion([sujeto(['In', 'conclusion,', these, data, support, the, hypothesis, that, hepatosteatosis]), verbo([caused]), complemento([by, 'CDD', is, associated, with, more, severe, 'ConA-induced', hepatitis, due, to, a, predominant, shift, toward, 'Th1', response])]). relacion([sujeto(['Although', 'hESC-derived', hematopoietic, progenitors]), verbo([have]), complemento([been, previously, identified, by, functional, 'assays,', their, phenotype, has, not, been, defined])]). relacion([sujeto(['These', cells, were, negative, for, 'lineage-specific', markers, '(', 'Lin(-)),']), verbo([expressed]), complemento(['KDR,', 'VE-cadherin,', and, 'CD105', endothelial, 'proteins,', and, expressed, 'GATA-2,', 'GATA-3,', 'RUNX1,', 'C-MYB', transcription, factors, that, typify, initial, stages, of, definitive, hematopoiesis, originating, from, 'endothelial-like', precursors])]). relacion([sujeto(['Acquisition', of, 'CD45', expression, by, 'CD34(+)CD43(+)CD45(-)Lin(-)', cells, was]), verbo([associated]), complemento([with, progressive, myeloid, commitment, and, a, decrease, of, 'B-lymphoid', potential])]). relacion([sujeto(['Horses', with, recurrent, airway, obstruction, '(', 'RAO)', present, many, similarities, with, human, asthmatics, including, airway, 'inflammation,', 'hyperresponsiveness,', reversible, 'obstruction,', and]), verbo([increased]), complemento(['NF-kappaB', expression])]). relacion([sujeto(['Studies', in, experimental, asthma, models]), verbo([have]), complemento([shown, that, transcriptions, factors, such, as, activator, 'protein-1', '(', 'AP-1),', 'GATA-3,', cyclic, 'AMP', response, element, binding, protein, '(', 'CREB)', and, 'CAAT/enhancer', binding, protein, '(', 'C/EBP)', may, also, play, an, important, role, in, airway, inflammation])]). relacion([sujeto(['The', purpose, of, this, study, was, to, measure, 'DNA']), verbo([binding]), complemento([activity, of, these, transcription, factors, in, the, airways, of, horses, with, 'RAO', and, to, compare, it, to, pulmonary, function, and, bronchoalveolar, lavage, fluid, '(', 'BALF)', cytology])]). relacion([sujeto(['Seven', horses, with, 'RAO', and, six, control, animals, were, studied, during, a, moldy]), verbo([hay]), complemento([challenge, and, after, 2, months, at, pasture])]). relacion([sujeto(['Pulmonary', 'function,', 'BALF', cytology, and, transcription, 'factors\'', activities, in, bronchial, brushings, were, measured, during]), verbo([hay]), complemento([and, pasture, exposures])]). relacion([sujeto(['During', moldy]), verbo([hay]), complemento(['challenge,', 'RAO-affected', horses, developed, severe, airway, obstruction, and, inflammation, and, a, significantly, higher, airway, 'AP-1', binding, activity, than, in, controls])]). relacion([sujeto(['After', 2, months, on, 'pasture,', pulmonary, function, and, airway, 'AP-1']), verbo([binding]), complemento([activity, were, not, different, between, 'RAO', and, control, horses])]). relacion([sujeto(['The', 'DNA']), verbo([binding]), complemento([activity, of, 'CREB', in, airways, of, 'RAO-affected', horses, increased, significantly, after, 2, months, at, pasture, and, became, higher, than, in, controls])]). relacion([sujeto(['A', significant, positive, correlation, was, detected, between, 'AP-1']), verbo([binding]), complemento([activity, and, indicators, of, airway, obstruction, and, inflammation])]). relacion([sujeto(['Airway', 'GATA-3,', 'CEBP', and, 'CREB']), verbo([binding]), complemento([activities, were, negatively, correlated, with, indices, of, airway, obstruction])]). relacion([sujeto(['However,', contrarily, to, 'CREB']), verbo([binding]), complemento(['activity,', 'GATA-3', and, 'CEBP', binding, activities, were, not, different, between, 'RAO', and, control, horses, and, were, unaffected, by, changes, in, environment])]). relacion([sujeto(['These', data, support, the, view, that, 'AP-1', and, 'CREB', play, a, role, in]), verbo([modulating]), complemento([airway, inflammation, in, horses, with, 'RAO'])]). relacion([sujeto(['Oestrogen', '(', 'E)', is, essential, for, normal, and, cancer, development, in, the, 'breast,', while, 'anti-oestrogens']), verbo([have]), complemento([been, shown, to, reduce, the, risk, of, the, disease])]). relacion([sujeto(['Previous', expression, profiles, of, the, response, to, 'E']), verbo([have]), complemento([been, performed, on, tumour, cell, 'lines,', in, the, absence, of, stroma])]). relacion([sujeto(['After', 2, 'weeks,', when, epithelial, proliferation, is, 'minimal,', 'one-third', of, the, mice, were, treated, with, 17, 'beta-oestradiol', '(', 'E2)', to, give, human, 'luteal-phase', levels, in, the, 'mouse,', which, we]), verbo([have]), complemento([previously, shown, to, induce, maximal, epithelial, cell, proliferation])]). relacion([sujeto(['E2', treatment, was]), verbo([found]), complemento([to, represent, the, largest, source, of, variation, in, gene, expression, and, 'cross-species', hybridization, of, mouse, 'RNA', from, xenograft, samples, was, demonstrated, to, be, negligible])]). relacion([sujeto(['Known', 'E2-responsive', genes, '(', such, as, 'TFF1', and, 'AREG),', and, genes, thought, to, be]), verbo([involved]), complemento([in, breast, cancer, metastasis, '(', including, 'mammoglobin,', 'KRT19', and, 'AGR2),', were, upregulated, in, response, to, 'E', treatment])]). relacion([sujeto(['In', 'addition,', genes, that, are, normally]), verbo([expressed]), complemento([in, the, myoepithelium, and, extracellular, matrix, that, maintain, the, tissue, microenvironment, were, also, differentially, expressed])]). relacion([sujeto(['This']), verbo([suggests]), complemento([that, the, response, to, oestrogen, in, normal, breast, is, highly, dependent, upon, 'epithelial-stromal/myoepithelial', interactions, which, maintain, the, tissue, microenvironment, during, epithelial, cell, proliferation])]). relacion([sujeto(['Several', transcription, factors]), verbo([have]), complemento([been, implicated, in, the, inflammatory, process, in, 'asthma,', including, the, glucocorticoid, receptor, '(', 'GR),', 'NFkappaB,', 'Activator', 'Protein-1', '(', 'AP-1),', 'Nuclear', 'Factor', of, 'Activated', 'T-cells', '(', 'NF-AT),', cyclic, 'AMP', 'Response', 'Element', 'Binding', 'Protein', and, more, 'recently,', the, 'CCAAT/Enhancer', 'Binding', 'Protein', '(', 'C/EBP),', 'Peroxisome', 'Proliferator-activated', 'Receptor', '(', 'PPAR)', and, the, bZIP, transcription, 'factor,', 'Nrf2'])]). relacion([sujeto(['Could', a, pathological, 'de-regulation', of, one, of, these, transcription, factors, explain, the, broad, spectrum, of, asthma, pathology, and, can, their, modulation]), verbo([lead]), complemento([to, better, symptom, 'control?', 'Although', some, of, the, transcription, factors, seem, to, be, valid, targets, '(', 'NFkappaB,', 'Nrf2', or, 'STAT6)', or, tools, '(', 'PPARgamma,', -, alpha, and, 'C/EBP-alpha)', for, new, therapeutic, 'approaches,', since, many, transcription, factors, play, a, central, role, in, tissue, and, organ, 'homeostasis,', a, longterm, general, suppression, or, 'overexpression,', would, cause, severe, side, effects, in, other, organs])]). relacion([sujeto(['Cell', type, specific, application, of, decoy, or, antisense, oligonucleotides, for, 'NFkappaB,', 'Nrf2', or, 'STAT6,', or, specific, agonists, for, 'PPARgamma', and, -, alpha, may, help, to, control, the, inflammatory, response, in, lung, epithelial, cells, and, infiltrated, immune, 'cells,', but, 'additional,', 'unwanted,', effects, on, other, resident, cells, of, the, lung, cannot, be, excluded, and, a, beneficial, effect, over, known, 'anti-asthma', drugs]), verbo([has]), complemento([first, to, be, proven])]). relacion([sujeto(['The', 'Mixed-Lineage', 'Leukemia', '(', 'MLL)', 'gene,', a, mammalian, homolog, of, the, 'Drosophila', 'trithorax,', is, implicated, in]), verbo([regulating]), complemento([the, maintenance, of, 'Hox', gene, expression, and, hematopoiesis])]). relacion([sujeto(['Furthermore,', histone, modifications, at, the, 'Th2', cytokine, gene, loci, were, not, properly]), verbo([maintained]), complemento([in, 'MLL(+/-)', memory, 'Th2', cells])]). relacion([sujeto(['The', reduced, expression, of, 'MLL', in, memory, 'Th2', cells, resulted, in]), verbo([decreased]), complemento(['GATA3', expression, accompanied, with, impaired, 'GATA3', locus, histone, modifications])]). relacion([sujeto(['Memory', 'Th2', 'cell-dependent', allergic, airway, inflammation, was]), verbo([decreased]), complemento([in, 'MLL(+/-)', 'Th2', 'cell-transferred', mice])]). relacion([sujeto(['Recent', studies]), verbo([have]), complemento([shown, a, 'Th2-biasing', effect, of, 'statins,', although, the, underlying, mechanism, has, not, been, identified])]). relacion([sujeto(['Exposure', of, 'DCs', to, simvastatin]), verbo([induced]), complemento([the, differentiation, of, a, distinct, subset, of, 'DCs', characterized, by, a, high, expression, of, 'B220'])]). relacion([sujeto(['The', 'Th2-biased', transcription, factor, profile]), verbo([induced]), complemento([by, 'simvastatin-treated', 'DCs', also, was, accompanied, by, increased, 'Th2', '(', 'IL-4,', 'IL-5,', and, 'IL-13)', and, decreased, 'Th1', '(', 'IFN-gamma)', cytokine, secretion, from, the, 'T', cells])]). relacion([sujeto(['The', 'Th2-promoting', effect, of, simvastatin, was]), verbo([found]), complemento([to, depend, on, the, chitinase, family, member, 'Ym1,', known, to, be, a, lectin])]). relacion([sujeto(['Peripheral', blood, mononuclear, cells, '(', 'PBMCs)', were, 'isolated,', 'cultured,', and]), verbo([activated]), complemento([with, 'PMA/ionomycin'])]). relacion([sujeto(['Splenocytes', were, 'isolated,', 'cultured,', and]), verbo([activated]), complemento([with, 'PMA/ionomycin'])]). relacion([sujeto(['The', 'T-bet/GATA-3', ratio, may]), verbo([provide]), complemento([a, surrogate, marker, of, 'T1/T2', cytokine, balance])]). relacion([sujeto(['In', the, control, 'group,', the, mRNA, ratio, of, 'T-bet', to, 'GATA-3', '(', 0.73, +, /, -, 0.32, ')', was, significantly]), verbo([increased]), complemento([compared, with, the, asthmatic, group, '(', 0.06, +, /, -, 0.09, ',', 'P', &, 'lt;', 0.01, ')'])]). relacion([sujeto(['Mast', cells, are, able, to, produce, a, huge, panel, of, mediators, including, the, 'Th2-type', cytokine, 'IL-9,', which, is, considered, to, be, a, key, mediator, for, the, pathogenesis, of, allergic, 'asthma,', but, detailed, information, on, the, regulation, of, 'IL-9', transcription, in, mast, cells]), verbo([has]), complemento([been, scarce])]). relacion([sujeto(['Herein', we]), verbo([provide]), complemento([evidence, that, the, 'erythroid/myeloid', transcription, factor, 'GATA-1,', which, is, not, expressed, in, 'Th2', 'cells,', is, a, potent, activator, of, 'IL-9', expression, in, murine, bone, 'marrow-derived', mast, cells, '(', 'BMMC)'])]). relacion([sujeto(['As', transactivation]), verbo([mediated]), complemento([by, 'GATA-1', is, also, sensitive, to, inhibition, of, p38, 'MAP', 'kinase,', and, 'GATA-1', is, a, target, for, p38, 'MAP', 'kinase-mediated', phosphorylation, in, 'vitro,', we, conclude, that, both, signaling, molecules, represent, a, part, of, a, mast, 'cell-specific', signaling, network, that, regulates, the, expression, of, 'IL-9'])]). relacion([sujeto(['Imiquimod', is, an, 'imidazoquinoline,', which, class, of, compounds, are, known, to]), verbo([have]), complemento([antiviral, and, antitumoural, properties])]). relacion([sujeto(['In', recent, 'studies,', it, was, shown, that, imiquimod]), verbo([modulates]), complemento([the, 'T', helper, cell, type, 'Th1/Th2', response, by, inducing, the, production, of, 'Th1', cytokines, like, 'IFN-gamma,', and, by, inhibiting, the, 'Th2', cytokines, like, interleukin, '(', 'IL)-4'])]). relacion([sujeto(['Several', investigators]), verbo([have]), complemento([shown, that, 'T-bet', and, 'GATA-3', are, master, 'Th1', and, 'Th2', regulatory, transcription, factors])]). relacion([sujeto(['This', study, investigated, whether, imiquimod, treatment]), verbo([inhibited]), complemento([airway, inflammation, by, modulating, transcription, factors, 'T-bet', and, 'GATA-3'])]). relacion([sujeto(['It', was, demonstrated, that, imiquimod, 1, ')', attenuated, 'OVA']), verbo([induced]), complemento([airway, 'inflammation;', 2, ')', diminished, the, degree, of, airway, hyperresponsiveness, '(', 'AHR);', 3, ')', decreased, the, 'Th2', type, cytokines, and, increased, 'Th1', type, cytokines, mRNA, and, protein, 'levels;', 4, ')', modulated, the, 'Th1/Th2', reaction, by, inhibiting, 'GATA-3', production, and, increasing, 'T-bet', production])]). relacion([sujeto(['Imiquimod', treatment]), verbo([inhibits]), complemento(['OVA', induced, airway, inflammation, by, modulating, key, master, switches, 'GATA-3', and, 'T-bet', that, result, in, committing, 'T', helper, cells, to, a, 'Th1', phenotype])]). relacion([sujeto(['To', explore, whether, local, blockade, of, 'T-box']), verbo([expressed]), complemento([in, 'T', cells, '(', 'T-bet)', expression, in, the, lungs, could, lead, to, airway, inflammation])]). relacion([sujeto(['The', expression, of, 'T-bet', mRNA, and, protein, in, the, lungs, of, the, rats, in, the, antisense, group, were]), verbo([inhibited]), complemento([effectively])]). relacion([sujeto(['The', level, of, 'IL-4', and, 'IL-5', in, the, 'BALF', in, the, antisense, and, 'OVA-sensitized', groups, were, 'elevated,', but, the, level, of, 'IFN-gamma']), verbo([decreased]), complemento([markedly])]). relacion([sujeto(['Antisense', 'ODN-induced', local, blockade, of, 'T-bet', expression]), verbo([leads]), complemento([to, airway, inflammation, with, a, selective, alteration, in, patterns, of, cytokine, expression, and, recruitment, of, eosinophil, cells, similar, to, that, in, the, 'OVA-sensitized', animals])]). relacion([sujeto(['Exhaled', 'NO', significantly]), verbo([decreased]), complemento([within, 3, weeks, of, therapy, in, patients, with, allergic, and, 'intrinsic,', moderate, and, severe, asthma])]). relacion([sujeto(['Interleukin-10', '(', 'IL-10)-secreting', peripheral, blood, mononuclear, cells, '(', 'PBMC)']), verbo([increased]), complemento([within, 3, weeks, of, therapy, in, six, of, 11, 'patients,', whereas, transforming, growth, 'factor-beta(1)-secreting', 'PBMC', remained, stable])]). relacion([sujeto(['Furthermore,', monocyte, 'activation,', assessed, by, 'CD80', expression, significantly]), verbo([decreased]), complemento([during, therapy])]). relacion([sujeto(['FOXP3', and, 'GATA-3', mRNA, expression, in, 'CD4(+)', 'T', cells, did, not, 'change,', while, 'interferon-gamma', and, 'IL-13', mRNA, expression]), verbo([decreased]), complemento([in, eight, of, 10, patients])]). relacion([sujeto(['Previous', studies]), verbo([have]), complemento([determined, that, 'Slc11a1', was, an, excellent, candidate, gene, for, 'Ses1'])]). relacion([sujeto(['Gene', expression, profiling, demonstrated, that, 129, 'S6', mice, had, a, significant, 'up-regulation', of, proinflammatory, genes]), verbo([associated]), complemento([with, macrophage, activation, at, day, 10, 'postinfection,', followed, by, a, gradual, increase, in, immunoglobulin, 'transcripts,', whereas, 129, 'S6-Slc11a1(tm1Mcg)', mice, had, higher, levels, of, immunoglobulins, earlier, in, the, infection])]). relacion([sujeto(['Quantitative', reverse, 'transcription-PCR', revealed, an]), verbo([increase]), complemento([in, 'Th1', cytokine, '(', 'Ifng', and, 'Il12)', and, 'Th1-specific', transcription, factor, 'Tbx21', expression, during, infection, in, both, the, 129, 'S6', and, 129, 'S6-Slc11a1(tm1Mcg)', strains])]). relacion([sujeto(['However,', the, expression, of, 'Gata3,', a, transcription, factor]), verbo([involved]), complemento([in, 'Th2', 'polarization,', 'Cd28,', and, 'Il4', was, markedly, increased, in, 'Slc11a1-deficient', mice, during, 'infection,', suggesting, a, predominant, 'Th2', phenotype, in, 129, 'S6-Slc11a1(tm1Mcg)', animals, following, 'S'])]). relacion([sujeto(['The', presence, of, a, 'Th2', bias, in, 'Slc11a1-deficient', mice, is]), verbo([associated]), complemento([with, improved, bacterial, clearance])]). relacion([sujeto(['Airway', remodeling, is, an, important, feature, of, chronic, asthma, that]), verbo([causes]), complemento([irreversible, airflow, obstruction])]). relacion([sujeto(['The', degrees, of, subepithelial, fibrosis, and, airway, smooth, muscle, hyperplasia, after, repeated, allergen, exposure, were, significantly]), verbo([enhanced]), complemento([in, mice, overexpressing, 'GATA-3,', compared, with, 'wild-type', mice])]). relacion([sujeto(['Eosinophilic', airway, inflammation]), verbo([increased]), complemento([in, mice, overexpressing, 'GATA-3,', but, decreased, in, mice, overexpressing, 'T-bet', after, repeated, allergen, exposure])]). relacion([sujeto(['Lung', transforming, growth, 'factor-beta', and, eotaxin, levels, were]), verbo([associated]), complemento([with, the, degree, of, subepithelial, fibrosis, and, eosinophilic, airway, 'inflammation,', respectively])]). relacion([sujeto(['Overall,', the, results, indicate, that, development, of, airway, remodeling, is]), verbo([regulated]), complemento([by, the, lung, 'Th1/Th2', bias, induced, by, 'GATA-3', and, 'T-bet'])]). relacion([sujeto(['Frequent', users, of, smokeless, tobacco, '(', 'ST)']), verbo([have]), complemento([an, increased, risk, for, developing, oral, cancer])]). relacion([sujeto(['Nicotine', and, its, derivatives, may, contribute, to, tumorigenesis, through, stimulation, of, nicotinic, acetylcholine, receptors, '(', 'nAChRs)', in]), verbo([target]), complemento([cells])]). relacion([sujeto(['Emerging', evidence, indicates, that, nAChRs, can, be]), verbo([stimulated]), complemento([by, the, 'nicotine-derived', nitrosamines, 4, -, '(', 'methylnitrosamino)-1-(3-pyridyl)-1-butanone', '(', 'NNK)', and, 'N\'-nitrosonornicotine', '(', 'NNN)', that, can, induce, oral, cavity, tumors, in, laboratory, animals])]). relacion([sujeto(['We', used, 'Het-1A', cells, that, were]), verbo([found]), complemento([to, express, 'alpha3,', 'alpha5,', 'alpha7,', 'alpha9,', beta2, and, beta4, nAChR, subunits])]). relacion([sujeto(['Both', 'NNK', and, 'NNN', competed, with, nicotinic, radioligands, for]), verbo([binding]), complemento([to, 'Het-1A', cells])]). relacion([sujeto(['NNK', showed, a, higher, than, 'NNN', affinity, to, the, '[', 3, 'H]nicotine-labeled']), verbo([binding]), complemento(['sites,', and, 'NNN-to', the, '[', 3, 'H]epibatidine-sensitive', nAChRs])]). relacion([sujeto(['NNK', and, 'NNN']), verbo([increased]), complemento([proliferative, potential, of, 'Het-1A', cells, and, produced, an, 'anti-apoptotic', 'effect,', which, was, alleviated, by, antagonists])]). relacion([sujeto(['Treatment', of, 'Het-1A', cells, with, either, 'NNK', or, 'NNN']), verbo([led]), complemento([to, acquisition, of, capability, of, anchorage, independent, growth, and, ability, to, produce, tumors, in, nude, 'mice,', both, of, which, can, be, by, inhibited, by, antagonists])]). relacion([sujeto(['The', 'Het-1A', cells]), verbo([stimulated]), complemento([with, nitrosamines, showed, multifold, increases, of, the, mRNA, transcripts, encoding, 'PCNA', and, 'Bcl-2,', and, upregulated, expression, of, the, transcription, factors, 'GATA3,', nuclear, 'factor-kappaB,', and, 'STAT-1'])]). relacion([sujeto(['The', 'STAT-1', 'protein-binding', activity]), verbo([induced]), complemento([by, 'NNK', and, 'NNN', correlated, with, elevated, gene, expression])]). relacion([sujeto(['A', receptive, endometrial, environment]), verbo([requires]), complemento([adequate, immunological, tolerance, to, protect, the, implanting, embryo, from, maternal, immune, rejection])]). relacion([sujeto(['In', 'contrast,', mRNAs, encoding, 'T', cell, transcription, factors, 'T-bet', and, 'GATA3,']), verbo([associated]), complemento([with, differentiation, of, 'Th1', and, 'Th2', 'CD4+', 'T', cells, 'respectively,', were, unchanged])]). relacion([sujeto(['Cytokines', influencing, 'Th1', and, 'Th2', cell, 'differentiation,', including, 'IFNgamma,', 'IL-2,', 'IL-4,', 'IL-5,', 'IL-10', and, 'IL-12p40,', as, well, as, dendritic, 'cell-regulating', cytokines, 'IL-1alpha,', 'IL-1beta,', 'IL-6,', 'LIF,', 'GM-CSF', and, 'TNFalpha', were, also]), verbo([expressed]), complemento([similarly, regardless, of, fertility, status])]). relacion([sujeto(['The']), verbo([finding]), complemento([of, reduced, endometrial, 'Foxp3', implicates, impaired, differentiation, of, uterine, 'T', cells, into, the, 'Treg', phenotype, as, a, key, determinant, of, fertility, in, women])]). relacion([sujeto([',', if, a, 'Th', lineage, was]), verbo([inhibited]), complemento([or, enhanced, in, adult, 'animals,', a, similar, phenomenon, was, observed, in, neonates])]). relacion([sujeto(['Antigen-specific', 'IFN-gamma', production, was]), verbo([increased]), complemento([50, -, 100, -, fold, in, 'STAT6-deficient', 'neonates,', achieving, levels, similar, to, those, of, 'STAT6-deficient', adults])]). relacion([sujeto(['The', 'TCR', signals, for, the]), verbo([release]), complemento([of, 'CD4', effector, function, are, poorly, understood])]). relacion([sujeto(['However,', when, 'Itk', is]), verbo([required]), complemento([during, 'Th2', development, is, unclear])]). relacion([sujeto(['We']), verbo([suggest]), complemento([that, the, liberation, of, effector, function, is, tightly, controlled, through, qualitative, changes, in, 'TCR', 'signals,', facilitating, postdifferentiation, regulation, of, cytokine, responses])]). relacion([sujeto(['GATA2', is]), verbo([expressed]), complemento([in, the, pituitary, during, development, and, in, adult, gonadotropes, and, thyrotropes])]). relacion([sujeto(['These', mice]), verbo([have]), complemento([reduced, secretion, of, gonadotropins, basally, and, in, response, to, castration, 'challenge,', although, the, mice, are, fertile])]). relacion([sujeto(['Mutants']), verbo([have]), complemento([fewer, thyrotrope, cells, at, 'birth,', male, 'Gata2-deficient', mice, exhibit, growth, delay, from, 3, -, 9, wk, of, 'age,', and, adult, mutants, produce, less, 'TSH', in, response, to, severe, hypothyroidism, after, radiothyroidectomy])]). relacion([sujeto(['Gata2-deficient', mice, exhibit, elevated, levels, of, 'Gata3', transcripts, in, the, pituitary, 'gland,']), verbo([suggesting]), complemento([that, 'GATA3', can, compensate, for, 'GATA2'])]). relacion([sujeto(['Here', we, show, that, 'CD4+', cells, from, 'T-bet-/-', mice, are, skewed, toward, 'Th2', differentiation, by, high, endogenous, 'GATA-3', levels, but, exhibit, virtually, normal, 'Th1', differentiation]), verbo([provided]), complemento([that, 'GATA-3', levels, are, regulated, at, an, early, stage, by, 'anti-interleukin', '(', 'IL)-4', blockade, of, 'IL-4', receptor, '(', 'R)', signaling])]). relacion([sujeto(['In', related, 'studies,', we, show, that, the, negative, effect, of, 'GATA-3', on, 'Th1', differentiation, in, 'T-bet-/-', cells, arises, from, its, ability, to]), verbo([suppress]), complemento(['STAT4', 'levels,', because, if, this, is, prevented, by, a, 'STAT4-expressing', 'retrovirus,', normal, 'Th1', differentiation, is, observed])]). relacion([sujeto(['Finally,', we, show, that, retroviral, 'T-bet', expression, in, developing, and, established, 'Th2', cells]), verbo([leads]), complemento([to, 'down-regulation', of, 'GATA-3', levels])]). relacion([sujeto(['These', findings]), verbo([lead]), complemento([to, a, model, of, 'T', cell, differentiation, that, holds, that, naive, 'T', cells, tend, toward, 'Th2', differentiation, through, induction, of, 'GATA-3', and, subsequent, 'down-regulation', of, 'STAT4/IL-12Rbeta2', chain, unless, 'GATA-3', levels, or, function, is, regulated, by, 'T-bet'])]). relacion([sujeto(['Thus,', the, principal, function, of, 'T-bet', in, developing, 'Th1', cells, is, to, negatively]), verbo([regulate]), complemento(['GATA-3', rather, than, to, positively, regulate, the, 'IFNG', gene])]). relacion([sujeto(['Although', various, transcription, factors, were, defined, to]), verbo([enhance]), complemento(['IL-10,', the, molecular, mechanism, for, the, initiation, of, 'Il-10', 'transcription,', remains, unknown])]). relacion([sujeto(['We', showed, that, ectopic, expression, of, 'GATA-3', in, naive, primary, 'CD4+', 'T', cells]), verbo([enhanced]), complemento([expression, of, 'IL-10', by, these, cells, and, uncovered, a, possible, mechanism, for, this, effect])]). relacion([sujeto(['We']), verbo([found]), complemento([that, 'GATA-3', induced, changes, of, the, chromatin, structure, at, the, 'Il-10', locus, and, that, these, changes, occur, even, in, the, absence, of, 'IL-4'])]). relacion([sujeto(['Furthermore', we]), verbo([found]), complemento([that, in, the, presence, of, 'GATA-3', the, histones, at, the, 'Il-10', locus, become, acetylated])]). relacion([sujeto(['Despite', being]), verbo([recruited]), complemento([in, vivo, to, two, locations, on, the, 'Il-10', 'locus,', 'GATA-3', did, not, transactivate, the, 'IL-10', promoter])]). relacion([sujeto(['We', therefore]), verbo([suggest]), complemento([a, key, role, of, 'GATA-3', in, instructing, 'Il-10', gene, expression, in, primary, 'CD4+', 'T', 'cells,', possibly, by, switching, and, stabilizing, the, 'Il-10', locus, into, a, transcriptionally, competent, status])]). relacion([sujeto(['We']), verbo([report]), complemento([here, on, a, girl, and, her, father, with, 'HDR', syndrome, '(', 'Hypoparathyroidism,', sensorineural, 'Deafness', and, 'Renal', anomaly, 'syndrome)'])]). relacion([sujeto(['This', study]), verbo([provides]), complemento([new, biologic, information, concerning, differences, within, hormone, 'receptor-positive', breast, cancers, and, a, means, of, predicting, 'long-term', outcomes, in, 'tamoxifen-treated', patients])]). relacion([sujeto(['GATA-3', '(', 'GATA']), verbo([binding]), complemento([protein, 3, ')', and, the, 'proto-oncogene', 'c-maf', are, 'Th2-regulating', transcription, factors, that, control, the, expression, of, interleukin, '(', 'IL)-4', and, 'IL-5,', while, 'T-bet', '(', 'T-box', expressed, in, 'T', 'cells)', is, a, 'Th1-specific', transcription, factor, that, controls, the, expression, of, interferon, '(', 'IFN-gamma)'])]). relacion([sujeto(['Allergen', provocation, in, asthmatics]), verbo([induces]), complemento([a, 'Th2-dominated', cytokine, 'profile,', but, so, far, it, is, unknown, whether, the, skewed, cytokine, expression, is, reflected, by, the, expression, of, the, respective, transcriptional, regulators])]). relacion([sujeto(['In', 'BAL', cells, of, 'asthmatics,', the, mRNA, expression, of, all, transcription, factors, was]), verbo([increased]), complemento([after, allergen, challenge])]). relacion([sujeto(['In', bronchial, 'biopsies,', the, basal, expression, of, 'GATA-3', was]), verbo([increased]), complemento([in, asthmatics, compared, to, healthy, controls, but, decreased, after, allergen, challenge])]). relacion([sujeto(['Compared', to, sham, 'challenge,', the, percentage, of, 'IL-5+/CD4+', 'BAL', 'T', cells, was]), verbo([increased]), complemento([after, allergen, challenge, in, asthmatics, while, the, percentage, of, 'IFN-gamma+/CD4+', and, 'IFN-gamma+/CD8+', 'T', cells, was, decreased])]). relacion([sujeto(['Segmental', allergen, challenge, in, asthmatics]), verbo([leads]), complemento([to, increased, 'GATA-3,', 'c-maf', and, 'T-bet', expression, in, 'BAL', cells, but, not, in, bronchial, biopsies])]). relacion([sujeto(['Indeed,', when, we, examined, the, cytokine, profile, of, a, cohort, of, 'filaria-infected', '(', n, =, 10, ')', and, uninfected, '(', n, =, 10, ')', individuals, in, response, to, live, 'infective-stage', larvae, or, microfilariae, of, 'Brugia', 'malayi,', we]), verbo([found]), complemento([significant, impairment, of, both, 'Th1', and, 'Th2', cytokines, characterized, by, diminished, production, of, 'IFN-gamma,', 'TNF-alpha,', 'IL-4,', 'IL-5,', and, 'IL-10', in, infected, patients])]). relacion([sujeto(['Second,', regulatory, 'networks,', as, evidenced, by, significantly]), verbo([increased]), complemento([expression, of, 'Foxp3', '(', natural, regulatory, 'T', cell, 'marker)', and, regulatory, effectors, such, as, 'TGF-beta,', 'CTLA-4,', 'PD-1,', 'ICOS,', and, indoleamine, 2, ',', 3, -, dioxygenase, play, an, important, role, in, immunosuppression])]). relacion([sujeto(['Third,', the, compromise, of, effector, 'T', cell, function, is]), verbo([mediated]), complemento([by, the, enhanced, induction, of, 'anergy-inducing', factors, 'cbl-b,', 'c-cbl', '(', cbl, is, abbreviation, for, 'Casitas', 'B', 'lymphoma),', 'Itch,', and, 'Nedd4'])]). relacion([sujeto(['Studies']), verbo([have]), complemento([shown, that, 'T', helper, type, 2, '(', 'Th2)', cytokines, produced, by, both, 'T', cells, and, mast, cells, in, the, airway, contribute, substantially, to, the, initiation, of, inflammation, in, both, experimental, and, human, bronchial, asthma])]). relacion([sujeto(['Although', there, were, no, differences, in, the, types, of, infiltrating, cells, between, 'GATA-3-Tg/OVA-Tg', and, 'GATA-3-non-Tg/OVA-Tg', mice, and, no, significant]), verbo([increase]), complemento([in, 'IgE', level, in, either, group, compared, with, nontreated, 'mice,', the, response, after, 'ACh', inhalation, was, significantly, elevated, in, 'GATA-3-Tg/OVA-Tg', on, the, seventh, day, of, intranasal, treatment, with, 'OVA'])]). relacion([sujeto(['This', hyperresponsiveness, was]), verbo([inhibited]), complemento([by, 5, -, lipoxygenase, inhibitor, and, 'IL-13', 'neutralization,', suggesting, that, airway, responses, were, induced, through, 'IL-13', and, leukotriene, pathway])]). relacion([sujeto(['In', 'conclusion,', airway, 'hyperresponsiveness,', a, characteristic, of, bronchial, 'asthma,', is]), verbo([regulated]), complemento([at, the, level, of, 'GATA-3', transcription, by, 'T', lymphocytes, in, vivo])]). relacion([sujeto(['Our', results, show, that, 'CTLA-4']), verbo([inhibits]), complemento(['GATA-3', mRNA, expression, and, 'Th2', cell, differentiation])]). relacion([sujeto(['GATA-3', mRNA, expression, is]), verbo([inhibited]), complemento([when, 'CD4+', cells, are, stimulated, under, both, neutral, '(', i])]). relacion([sujeto(['Hence', 'CTLA-4', might, affect, the, 'IL-4/signal', transducer, and, activator, of, 'transcription-6', '(', 'STAT6)', pathway]), verbo([leading]), complemento([to, 'GATA-3', mRNA, 'up-regulation'])]). relacion([sujeto(['We', 'found,', 'indeed,', that, 'CTLA-4', engagement]), verbo([inhibits]), complemento(['STAT6', activation, leaving, unaffected, the, 'STAT6', protein, level])]). relacion([sujeto(['Moreover,', 'CTLA-4', engagement, drastically]), verbo([inhibits]), complemento(['IL-4Ralpha', mRNA, and, protein, 'up-regulation', under, 'Th2-polarizing', conditions])]). relacion([sujeto(['Thus,', 'CTLA-4', exerts, a, tight, control, on, 'Th2', cell, differentiation, by, negatively]), verbo([regulating]), complemento([both, the, 'CD3/CD28', and, the, 'IL-4/STAT6', pathways])]). relacion([sujeto(['Th2', 'cells,', capable, of, producing, 'IL-4,', 'IL-5', and, 'IL-13,', are]), verbo([involved]), complemento([in, humoral, immunity, against, extracellular, pathogens, and, in, the, induction, of, asthma, and, other, allergic, diseases])]). relacion([sujeto(['In', this, 'review,', we, summarize, recent]), verbo([reports]), complemento([regarding, the, transcription, factors, involved, in, 'Th2', differentiation, and, cell, 'expansion,', including, 'Stat5,', 'Gfi-1', and, 'GATA-3'])]). relacion([sujeto(['Enhanced', 'Stat5', signaling]), verbo([induces]), complemento(['Th2', differentiation, independent, of, 'IL-4', 'signaling;', although, it, does, not, 'up-regulate', 'GATA-3', 'expression,', it, does, require, the, presence, of, 'GATA-3', for, its, action])]). relacion([sujeto(['Gfi-1,']), verbo([induced]), complemento([by, 'IL-4,', promotes, the, expansion, of, 'GATA-3-expressing', cells])]). relacion([sujeto(['Analysis', of, conditional, 'Gata3', knockout, mice, confirmed, the, critical, role, of, 'GATA-3', in, 'Th2', cell, differentiation, '(', both, 'IL-4', dependent, and, 'IL-4', 'independent)', and, in, 'Th2', cell, proliferation, and, also, showed, the, importance, of, basal, 'GATA-3', expression, in]), verbo([inhibiting]), complemento(['Th1', differentiation])]). relacion([sujeto(['Patients', with, active, lupus, nephritis]), verbo([have]), complemento([increased, 'T-bet', and, depressed, 'GATA-3', expression, in, the, urinary, sediment, and, kidney, 'tissue,', indicating, a, predominant, 'Th1', type, of, 'T-lymphocyte', activation])]). relacion([sujeto(['There']), verbo([have]), complemento([been, substantial, numbers, of, reports, on, 'T', cell, function, in, aged, mice, and, 'humans,', such, as, on, the, production, of, 'Th1', and, 'Th2', 'cytokines,', but, the, results, show, considerable, variation, and, contradictions])]). relacion([sujeto(['Chromatin', remodeling, of, the, 'Th2', cytokine, gene, locus, was]), verbo([found]), complemento([to, be, impaired])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, the, levels, of, 'Th2', cell, differentiation, and, resulting, 'Th2-dependent', immune, 'responses,', including, allergic, airway, 'inflammation,', decline, during, aging, through, defects, in, the, activation, of, the, 'ERK', 'MAPK', 'cascade,', expression, of, 'GATA3', protein, and, 'GATA3-dependent', chromatin, remodeling, of, the, 'Th2', cytokine, gene, locus])]). relacion([sujeto(['In', the, present, 'study,', we]), verbo([provide]), complemento([the, first, evidence, indicating, that, a, 'chromatin-remodeling', event, in, 'T', cells, is, impaired, by, aging])]). relacion([sujeto(['Here,', in, a, larger, sample, of, breast, cancer, cases, and, controls, '(', n, =, 1, ',', 322, /, n, =, 1, ',', 953, ')', nested, in, the, 'Nurses\'', 'Health', 'Study', 'cohort,', we, confirm, a, significant, association, '(', odds, 'ratio,', 1.41, ;, 95, '%', confidence, 'interval,', 1.1, -, 1.79, ')', and]), verbo([suggest]), complemento([a, molecular, model])]). relacion([sujeto(['To', help, understand, the, molecular, mechanism, by, which, this, variant, may, predispose, women, to, breast, 'cancer,', we, identified, nearby, transcription, factor]), verbo([binding]), complemento([sites])]). relacion([sujeto(['This', search, predicted, a]), verbo([binding]), complemento([site, for, the, 'GATA', family, of, transcriptional, regulators, adjacent, to, this, hPR, polymorphism])]). relacion([sujeto(['Importantly,', we]), verbo([found]), complemento(['GATA3,', 'GATA4,', and, 'GATA6', are, expressed, in, normal, breast, tissue, and, two, breast, cancer, cell, 'lines,', whereas, 'GATA5', is, minimally, expressed, in, normal, mammary, tissue, and, more, strongly, expressed, in, two, breast, cancer, cell, lines])]). relacion([sujeto(['This']), verbo([finding]), complemento([was, relevant, because, 'GATA5', bound, the, site, adjacent, to, the, +, 331, 'G/A', 'polymorphism,', and, activated, the, hPR, '(', -, 711, to, +, 822, ')', -, luciferase, reporter, plasmid, in, breast, cancer, cells])]). relacion([sujeto(['Overexpression', of, 'GATA5']), verbo([increased]), complemento([expression, of, the, endogenous, hPR, 'transcript,', and, 'GATA5', more, strongly, activated, an, hPR, promoter, construct, encoding, the, 'PR-B', isoform])]). relacion([sujeto(['Finally,', hPR, promoter, constructs, including, the, +, 331, 'A', were, more, strongly]), verbo([activated]), complemento([by, 'GATA5', than, constructs, including, +, 331, 'G'])]). relacion([sujeto(['Our', findings]), verbo([suggest]), complemento([that, 'GATA5', interacts, with, the, +, 331, 'G/A', polymorphism, to, stimulate, 'hPR-B', expression, in, mammary, 'cells,', which, may, contribute, to, breast, cancer, susceptibility])]). relacion([sujeto(['Opioids', and, cannabinoids, are, both]), verbo([associated]), complemento([with, 'analgetic,', 'psychotropic,', and, immunomodulatory, effects])]). relacion([sujeto(['It']), verbo([has]), complemento([been, suggested, that, both, systems, interact, on, multiple, levels])]). relacion([sujeto(['We', hypothesized, that, cannabinoids]), verbo([induce]), complemento([opioid, receptors, and, investigated, 'cannabinoid-dependent', expression, of, the, 'mu-opioid', receptor, subtype, in, a, human, 'T', cell, model])]). relacion([sujeto(['We']), verbo([report]), complemento([that, activation, of, the, peripheral, cannabinoid, receptor, type, 2, leads, to, a, de, novo, induction, of, 'mu-opioid', receptor, transcription, in, 'Jurkat', 'E6'])]). relacion([sujeto(['We', show, that, 'interleukin-4', is, transcriptionally]), verbo([induced]), complemento([in, response, to, cannabinoids, and, that, an, 'interleukin-4', receptor, antagonist, blocks, 'cannabinoid-dependent', induction, of, 'mu-opioid', 'receptors,', indicating, that, induced, expression, of, 'interleukin-4', is, required, in, this, process])]). relacion([sujeto(['Further', experiments, demonstrate, that, 'interleukin-4', then]), verbo([induces]), complemento([phosphorylation, of, 'STAT6,', which, directly, transactivates, the, 'mu-opioid', receptor, gene])]). relacion([sujeto(['In', 'addition,', 'STAT6']), verbo([induces]), complemento([expression, of, the, transcription, factor, 'GATA3,', which, also, contributes, to, 'mu-opioid', receptor, gene, transcription])]). relacion([sujeto(['The', responsive, promoter, region, of, the, human, 'mu-opioid', receptor, gene, with, the]), verbo([binding]), complemento([sites, for, both, factors, was, mapped, to, nt, -, 1001, to, -, 950])]). relacion([sujeto(['In', 'summary,', these, findings]), verbo([provide]), complemento([a, first, example, for, 'cannabinoid-opioid-interactions', in, cells, of, the, immune, system])]). relacion([sujeto(['Biolistic', delivery, of, genetic, vaccine, constructs, elicited, 'Th2-like', immunity, that, was]), verbo([associated]), complemento([with, inefficient, elimination, of, 'C'])]). relacion([sujeto(['The', results]), verbo([suggest]), complemento(['ELI', discovery, of, highly, protective, 'C'])]). relacion([sujeto([pneumoniae, vaccine, candidates]), verbo([requires]), complemento([tight, control, of, the, 'Th1', immunity, elicited, by, the, genetically, delivered, library, of, test, antigens])]). relacion([sujeto(['Notably,', 'SSc', 'PBCs', also, had]), verbo([increased]), complemento([expression, of, allograft, inflammatory, factor, '(', 'AIF1)', and, several, selectins, and, integrins, involved, in, cellular, adhesion, to, the, endothelium])]). relacion([sujeto(['Global', analysis, of, 284, known, biological, pathways, revealed, that, 13, were, differentially]), verbo([regulated]), complemento([in, 'SSc', 'PBCs,', including, two, pathways, '(', 'IL2RB', and, 'GATA3)', that, lead, to, 'T(H)2', polarization])]). relacion([sujeto(['Multiple', biological, pathways, were, differentially]), verbo([regulated]), complemento([in, 'SSc', 'PBCs,', but, a, common, thread, across, these, pathways, was, alterations, in, protein, tyrosine, kinase, 2, beta, and, 'mitogen-activated', protein, kinase, signalling])]). relacion([sujeto(['Although', the, 'SSc', 'PBC', gene, expression, profile, demonstrated, some, parallels, with, the, lupus, interferon, gene, 'signature,', there, was, also]), verbo([increased]), complemento([expression, of, transcripts, encoding, proteins, that, target, 'PBCs', to, the, 'endothelium,', which, might, be, relevant, to, the, vasculopathy, of, 'SSc'])]). relacion([sujeto(['We']), verbo([have]), complemento([found, that, 'Stat6', is, critical, for, the, expression, of, 'IL-5,', 'IL-10,', and, 'IL-13', by, 'NKT', cells])]). relacion([sujeto(['However,', the, 'Th2', 'cell-associated', transcription, factor, 'GATA-3,', normally]), verbo([induced]), complemento([by, 'Stat6', 'activation,', is, expressed, at, low, levels, in, 'NKT', cells])]). relacion([sujeto(['We']), verbo([found]), complemento([that, the, 'NFAT', family, member, 'NFAT2', is, selectively, increased, in, 'CD4+', 'NKT', cells])]). relacion([sujeto(['Expression', of, 'NFAT2']), verbo([increased]), complemento([the, expression, of, 'IL-4', in, both, 'NKT', cells, and, conventional, 'T', 'cells,', and, 'NFAT2', activated, 'IL-10', in, conventional, 'T', cells, but, not, in, 'NKT', cells])]). relacion([sujeto(['GATA-3', strongly]), verbo([activated]), complemento(['IL-4,', 'IL-5,', and, 'IL-13', expression, in, conventional, 'T', cells, but, had, comparatively, weak, effects, on, these, cytokines, in, 'NKT', cells])]). relacion([sujeto(['Thus,', 'NFAT2,', 'GATA-3,', and, 'Stat6']), verbo([have]), complemento([surprisingly, different, roles, in, 'NKT', cells, than, in, conventional, 'T', cells])]). relacion([sujeto(['We', propose, that, one, mechanism, by, which, 'CD4+', 'NKT', cells]), verbo([express]), complemento(['IL-4', independent, of, 'Stat6', is, via, increased, 'NFAT2', activity])]). relacion([sujeto(['There']), verbo([have]), complemento([been, a, few, reports, on, chromosomal, aberrations, of, 'MPNSTs;', 'however,', the, 'tumor-specific', alteration, remains, unknown])]). relacion([sujeto(['Frequent']), verbo([gains]), complemento([were, identified, on, 3, 'q13-26,', 5, 'p13-14,', and, 12, 'q11-23', and, frequent, losses, were, at, 1, 'p31,', 10, 'p,', 11, 'q24-qter,', 16, ',', and, 17])]). relacion([sujeto(['Microarray', 'CGH', revealed, frequent]), verbo([gains]), complemento([of, 'EGFR,', 'DAB2,', 'MSH2,', 'KCNK12,', 'DDX15,', 'CDK6,', and, 'LAMA3,', and, losses, of, 'CDH1,', 'GLTSCR2,', 'EGR1,', 'CTSB,', 'GATA3,', and, 'SULT2A1'])]). relacion([sujeto(['Some', evidence]), verbo([suggests]), complemento([that, this, may, be, due, to, suppression, of, 'anti-tumor', 'responses,', a, phenomenon, that, might, be, attributed, to, regulatory, 'T', cells])]). relacion([sujeto(['We', observed, that, p53]), verbo([induced]), complemento([both, 'IFN-gamma', and, 'IL-10', secretion])]). relacion([sujeto(['The', predominance, of, 'IL-10', production, indicated, that, regulatory, 'T', cells, directly]), verbo([participate]), complemento([in, modulating, the, 'anti-tumor', immune, response])]). relacion([sujeto(['These', results, may]), verbo([provide]), complemento([an, explanation, for, the, poor, prognosis, and, increased, recurrence, rate, in, patients, with, advanced, carcinoma])]). relacion([sujeto(['IL-5', is, a, key, regulator, of, eosinophilic, inflammation, and, is, selectively]), verbo([expressed]), complemento([by, 'antigen-activated', 'Th2', lymphocytes])]). relacion([sujeto(['An', important, role, for, the, proximal, 'AP-1', and, 'GATA', sites, in]), verbo([regulating]), complemento(['IL-5', transcription, is, generally, accepted, but, the, significance, of, an, adjacent, 'Ets/NFAT', site, has, remained, unclear])]). relacion([sujeto(['We']), verbo([have]), complemento([investigated, its, role, using, the, mouse, 'Th2', clone, 'D10'])]). relacion([sujeto(['Transcription', of, 'IL-5', reporter, gene, plasmids, could, be]), verbo([induced]), complemento([in, 'D10', cells, by, phorbol, myristate, 'acetate/cyclic', adenosine, monophosphate, '(', 'PMA/cAMP)', stimulation, and, significantly, further, enhanced, by, activation, of, the, 'mitogen-activated', protein, '(', 'MAP)', kinase, pathways])]). relacion([sujeto(['Strong', induction, of, 'IL-5', mRNA, was, also]), verbo([induced]), complemento([by, 'PMA/cAMP'])]). relacion([sujeto(['Mutagenesis', showed, that, the, 'Ets/NFAT', site, is, of, critical, importance, along, with, the, 'AP-1', and, 'GATA', sites, in]), verbo([regulating]), complemento(['IL-5', transcription, stimulated, by, 'PMA/cAMP', and, 'MAP', kinase, activation])]). relacion([sujeto(['AP-1', '(', 'c-Fos/c-Jun)', strongly]), verbo([induced]), complemento(['IL-5', transcription, and, dominant, negative, 'AP-1', constructs, confirmed, that, 'AP-1', plays, an, important, role, in, regulating, 'IL-5', expression])]). relacion([sujeto(['Ets1,', unlike, other, members, of, the, 'Ets/NFAT', 'family,', synergized, strongly, with, 'AP-1']), verbo([suggesting]), complemento([that, 'Ets1', is, the, family, member, which, functions, at, the, 'Ets/NFAT', site])]). relacion([sujeto(['AP-1/Ets1', transactivation, also]), verbo([stimulated]), complemento(['IL-5', mRNA, expression])]). relacion([sujeto(['Ets1']), verbo([binding]), complemento([to, the, proximal, promoter, 'region,', demonstrated, by, chromatin, 'immunoprecipitation,', was, stimulated, by, 'PMA/cAMP'])]). relacion([sujeto(['The', absolute, dependence, on, the]), verbo([binding]), complemento([sites, for, 'Ets1,', 'AP-1', and, 'GATA-3', together, with, the, strong, synergy, between, 'Ets1', and, 'AP-1', suggest, close, cooperative, interactions, between, the, three, transcription, factors, in, the, regulation, of, 'IL-5', expression, in, mouse, 'T', cells])]). relacion([sujeto(['GATA']), verbo([binding]), complemento([protein, 3, '(', 'GATA3)', is, a, transcriptional, activator, highly, expressed, by, the, luminal, epithelial, cells, in, the, breast])]). relacion([sujeto(['Here', we, did, a, 'meta-analysis', of, the, available, breast, cancer, cDNA, data, sets, on, a, cohort, of, 305, patients, and]), verbo([found]), complemento([that, 'GATA3', was, one, of, the, top, genes, with, low, expression, in, invasive, carcinomas, with, poor, clinical, outcome])]). relacion([sujeto(['Low', 'GATA3', expression, was]), verbo([associated]), complemento([with, higher, histologic, grade, '(', 'P', &, 'lt;', 0.001, ')', ',', positive, nodes, '(', 'P', =, 0.002, ')', ',', larger, tumor, size, '(', 'P', =, 0.03, ')', ',', negative, estrogen, receptor, and, progesterone, receptor, '(', 'P', &, 'lt;', 0.001, for, 'both),', and, 'HER2-neu', overexpression, '(', 'P', =, 0.03, ')'])]). relacion([sujeto(['Patients', whose, tumors]), verbo([expressed]), complemento([low, 'GATA3', had, significantly, shorter, overall, and, 'disease-free', survival, when, compared, with, those, whose, tumors, had, high, 'GATA3', levels])]). relacion([sujeto(['Our', data]), verbo([suggest]), complemento([that, immunohistochemical, analysis, of, 'GATA3', may, be, the, basis, for, a, new, clinically, applicable, test, to, predict, tumor, recurrence, early, in, the, progression, of, breast, cancer])]). relacion([sujeto(['Several', 'Th2', cytokines]), verbo([have]), complemento([potential, to, modulate, airway, 'inflammation,', in, particular, 'interleukin-13', which, induces, airway, hyperresponsiveness, independently, of, 'IgE', and, eosinophilia, in, animal, models])]). relacion([sujeto(['The', identification, of, transcription, factors, controlling, 'Th1,', 'Th2', and, 'T-regulatory', cell, '(', 'T(Reg))', development, further, support, the, 'Th2', hypothesis, since, 'GATA3', is, overexpressed, and, 'T-bet', underexpressed, in, the, asthmatic, airway, and, 'Foxp3', is]), verbo([induced]), complemento([in, asthma, by, corticosteroid, treatment])]). relacion([sujeto(['Our', previous, study, showed, that, 'DNA', vaccination, with, a, plasmid, vector, encoding, a, core, peptide, of, mucin1, '(', 'PDTRP)']), verbo([provided]), complemento([modest, protection, against, challenge, with, tumor, cells, that, expressed, mucin1, protein])]). relacion([sujeto(['We']), verbo([report]), complemento([here, that, a, 'DNA', vaccine, comprising, a, modified, 'PDTRP', plasmid, and, 'GM-CSF', coding, sequence, at, the, 'C-terminus', induced, better, protection, against, tumor, challenge])]). relacion([sujeto(['The']), verbo([increased]), complemento([protection, was, directly, correlated, with, a, stronger, 'PDTRP-specific', immune, response, induced, by, the, 'GM-CSF', fusion, plasmid])]). relacion([sujeto(['The', plasmid, encoding, 'GM-CSF', and, the]), verbo([target]), complemento(['PDTRP', antigen, induced, a, greater, 'PDTRP-specific', 'Th', 'proliferation,', 'antibodies,', and, cytotoxicity])]). relacion([sujeto(['Interestingly,', the, modified, plasmid, vaccine, predominantly]), verbo([enhanced]), complemento([the, type, 2, immune, responses, manifested, by, an, increased, 'IgG1', to, 'IgG2a', antibody, ratio, and, a, greater, induction, of, 'GATA-3', and, 'IL-4', mRNA, than, that, of, 'T-bet', and, 'IFN-gamma', mRNA, in, spleen, cells, from, vaccinated, mice])]). relacion([sujeto(['In', 'addition,', protection, against, tumor, challenge, in, vaccinated, mice, showed, that, there, was, no, significant, change, in, mice, survival, after, in, vivo, 'CD8+CTL', 'depletion,', indicating, that, antitumor, immunity, augmented, by, plasmid, encoding, 'GM-CSF', and]), verbo([target]), complemento(['PDTRP', gene, vaccine, was, dominated, by, 'Th2', immune, response])]). relacion([sujeto(['Both', variants, are, contemporarily]), verbo([expressed]), complemento([by, human, 'T', cells])]). relacion([sujeto(['Similar', effects, were, also, observed, on, polyclonally]), verbo([activated]), complemento([pure, naive, 'CD4+', 'T', cells])]). relacion([sujeto(['The', opposite, effects, of, 'CXCL10', and, 'CXCL4', on, 'TH1', and, 'TH2', cytokine, production, were]), verbo([inhibited]), complemento([by, an, 'anti-CXCR3', antibody, able, to, neutralize, both, 'CXCR3-A', and, 'CXCR3-B', and, were, apparently, related, to, the, activation, of, distinct, signal, transduction, pathways])]). relacion([sujeto(['Moreover,', 'CXCL10', upregulated, mRNA, levels, of, 'T-box']), verbo([expressed]), complemento([in, 'T', cells, and, downregulated, 'GATA-3', 'expression,', whereas, 'CXCL4', downregulated, 'T-box', expressed, in, 'T', cells, and, upregulated, 'GATA-3'])]). relacion([sujeto(['Finally,', 'CXCL4,', but, not, 'CXCL10,']), verbo([induced]), complemento([direct, activation, of, 'IL-5', and, 'IL-13', promoters])]). relacion([sujeto(['Anterior', chamber]), verbo([associated]), complemento([immune, deviation, '(', 'ACAID)', is, characterized, by, a, 'Th2', cell, response])]). relacion([sujeto(['GATA-3']), verbo([has]), complemento([been, shown, to, be, necessary, for, the, activation, of, 'Th2', cells])]). relacion([sujeto(['ACAID', was]), verbo([induced]), complemento([by, injection, of, 50, microg, interphotoreceptor, retinoid, binding, protein, '(', 'IRBP)', into, the, anterior, chamber, '(', 'AC)', of, 'Wistar', rats])]). relacion([sujeto(['The', 'DTH', reaction, was]), verbo([decreased]), complemento([7, days, after, 'IRBP', inoculation])]). relacion([sujeto(['GATA-3', expression, was, weak, at, both, mRNA, and, protein, levels, in, the, normal, 'spleen,', but, was, significantly]), verbo([increased]), complemento([on, day, 5, ',', 7, ',', 14, ',', and, 21, after, 'AC', injection, of, 'IRBP'])]). relacion([sujeto(['The', expression, of, 'GATA-3', is]), verbo([increased]), complemento([during, 'ACAID,', suggesting, that, 'GATA-3', may, be, involved, in, the, development, of, 'ACAID'])]). relacion([sujeto(['The', nephric, '(', 'Wolffian)', 'duct,', which, is, a, central, constituent, of, both, 'structures,', elongates, caudally, along, a, stereotypical, path, to, reach, the, hindlimb, level, where, it]), verbo([induces]), complemento([metanephros, '(', adult, 'kidney)', 'formation,', while, the, remaining, duct, gives, rise, to, the, male, genital, tract, '(', 'epidydimis,', vas, 'deferens)'])]). relacion([sujeto(['In', a, cDNA, microarray, screen, for, genes, specifically]), verbo([expressed]), complemento([in, the, 'pro/mesonephros', and, regulated, by, 'Pax', 'proteins,', we, identified, 'Gata3,', a, transcription, factor, gene, associated, with, 'hypoparathyroidism,', deafness, and, renal, anomaly, '(', 'HDR)', syndrome])]). relacion([sujeto(['Gata3', is, already]), verbo([expressed]), complemento([in, the, pronephric, 'anlage,', together, with, 'Pax2', and, 'Pax8,', suggesting, that, it, may, be, a, direct, 'Pax2/8', target, gene])]). relacion([sujeto(['Inactivation', of, 'Gata3', by, insertion, of, an, 'Ires-GFP', reporter, gene, resulted, in, a, massive]), verbo([increase]), complemento([in, nephric, duct, 'cellularity,', which, was, accompanied, by, enhanced, cell, proliferation, and, aberrant, elongation, of, the, nephric, duct])]). relacion([sujeto(['At', the, molecular, 'level,', the, nephric, duct, of, 'Gata3(-/-)', embryos, is, characterized, by, the]), verbo([loss]), complemento([of, 'Ret', expression, and, 'signaling,', which, may, contribute, to, the, guidance, defect, of, the, nephric, duct])]). relacion([sujeto(['Human', early, thymic, precursors]), verbo([have]), complemento([the, potential, to, differentiate, into, multiple, cell, 'lineages,', including, 'T', cells, and, plasmacytoid, dendritic, cells, '(', 'pDCs)'])]). relacion([sujeto(['Here', we, show, that]), verbo([triggering]), complemento([of, the, 'Notch1', signaling, pathway, by, 'Delta-like1', controls, the, 'T/pDC', lineage, decision, by, regulating, the, balance, between, these, factors])]). relacion([sujeto(['CD34+', 'CD1a-', thymic, progenitor, cells]), verbo([express]), complemento(['Notch1,', but, 'down-regulate', this, receptor, when, differentiating, into, pDCs])]). relacion([sujeto(['On', coculture, with, stromal, cell, lines]), verbo([expressing]), complemento([either, human, 'Delta-like1', '(', 'DL1)', or, 'Jagged1', '(', 'Jag1)', 'Notch', 'ligands,', thymic, precursors, express, 'GATA-3', and, develop, into, 'CD4+', 'CD8+', 'TCRalphabeta+', 'T', cells])]). relacion([sujeto(['A', set, of, 1.233, genes, was, differentially]), verbo([expressed]), complemento([between, basal, and, luminal, samples])]). relacion([sujeto(['Our', 'BCL', 'basal/luminal', signature, correctly, 're-classified', the, published, series, of, tumour, samples, that, originally, served, to, identify, the, molecular, 'subtypes,']), verbo([suggesting]), complemento([that, the, identified, markers, should, be, useful, for, tumour, classification, and, might, represent, promising, targets, for, disease, management])]). relacion([sujeto(['Glucocorticoid-induced', 'TNFR', 'family-related', protein, '(', 'GITR)', is]), verbo([expressed]), complemento([at, low, levels, on, resting, 'T', 'cells,', 'B', cells, and, macrophages, but, at, high, levels, on, regulatory, 'T', cells, '(', 'Treg)'])]). relacion([sujeto(['We']), verbo([report]), complemento([here, that, activation, of, 'GITR', signalling, by, 'anti-GITR', antibody, markedly, enhanced, the, induction, of, both, 'Th1', and, 'Th2', cytokine, production, by, naive, 'CD4+CD25-', 'T', cells])]). relacion([sujeto(['Consistent', with, this, 'observation,', 'anti-GITR', antibody, significantly]), verbo([enhanced]), complemento([the, expression, of, the, key, 'Th1', '(', 'T-bet)', and, 'Th2', '(', 'GATA3)', transcription, factors, in, vitro])]). relacion([sujeto(['Finally,', we, demonstrated, that, adoptive, transfer, of, 'CD4+GITR+', 'T', cells, effectively, abolished, airway, inflammation]), verbo([induced]), complemento([in, 'SCID', mice, reconstituted, with, 'CD4+GITR-', 'T', cells])]). relacion([sujeto(['Our', results, therefore]), verbo([provide]), complemento([direct, evidence, that, 'GITR', can, modulate, both, 'Th1-', and, 'Th2-mediated', inflammatory, 'diseases,', and, may, be, a, potential, target, for, therapeutic, intervention])]). relacion([sujeto(['The', noradrenergic, cell, type, is, characterized, by, the, expression, of, proteins]), verbo([involved]), complemento([in, the, 'biosynthesis,', 'transport,', and, secretion, of, noradrenaline, and, is, dependent, on, the, sequential, and, combinatorial, expression, of, numerous, transcription, 'factors,', including, 'Phox2a,', 'Phox2b,', 'dHAND,', 'GATA2,', 'GATA3,', and, 'MASH1'])]). relacion([sujeto(['In', this, 'study,', we, use, chromatin, immunoprecipitation, assays, to, identify]), verbo([target]), complemento([genes, of, the, 'Phox2', proteins, and, dHAND])]). relacion([sujeto(['All', three, proteins, are]), verbo([bound]), complemento([to, the, 'DBH', and, 'PHOX2B', promoter, regions, in, 'SH-SY5Y', neuroblastoma, cells])]). relacion([sujeto(['The', interaction, between, 'Phox2a', and, dHAND, is, analyzed, by, fluorescent, 'anisotropy,', which, demonstrates, that, dHAND]), verbo([causes]), complemento([an, eightfold, increase, in, the, affinity, of, 'Phox2a', for, its, recognition, sites, on, the, 'DBH', promoter, region])]). relacion([sujeto(['The', 'Phox2', proteins, are, not]), verbo([found]), complemento([on, the, genes, encoding, other, noradrenergic, enzymatic, or, transport, proteins, but, are, reciprocally, bound, to, each, 'other\'s', promoters, in, 'SH-SY5Y', cells])]). relacion([sujeto(['Together', with, 'Phox2a', and, 'Phox2b,', dHAND, is]), verbo([bound]), complemento([to, the, 'PHOX2B', promoter, and, is, also, associated, with, the, 'GATA2', and, eHAND, genes, in, the, absence, of, the, 'Phox2', proteins])]). relacion([sujeto(['The', 'Phox2', proteins, were]), verbo([found]), complemento([to, share, all, target, 'genes,', whereas, dHAND, binds, to, genes, independently, of, 'Phox2a'])]). relacion([sujeto(['We', recently, showed, that, dendritic, cells, '(', 'DCs)']), verbo([activated]), complemento([by, thymic, stromal, lymphopoietin, '(', 'TSLP)', prime, naive, 'CD4(+)', 'T', cells, to, differentiate, into, 'T', helper, type, 2, '(', 'Th2)', cells, that, produced, high, amounts, of, tumor, necrosis, 'factor-alpha', '(', 'TNF-alpha),', but, no, interleukin, '(', 'IL)-10'])]). relacion([sujeto(['Here', we]), verbo([report]), complemento([that, 'TSLP', induced, human, 'DCs', to, express, 'OX40', ligand, '(', 'OX40L)', but, not, 'IL-12'])]). relacion([sujeto(['TSLP-induced', 'OX40L', on, 'DCs', was]), verbo([required]), complemento([for, triggering, naive, 'CD4(+)', 'T', cells, to, produce, 'IL-4,', -, 5, ',', and, -, 13])]). relacion([sujeto(['We', further, revealed, the, following, three, novel, functional, properties, of, 'OX40L:', '(', 'a)', 'OX40L', selectively]), verbo([promoted]), complemento(['TNF-alpha,', but, inhibited, 'IL-10', production, in, developing, 'Th2', 'cells;', '(', 'b)', 'OX40L', lost, the, ability, to, polarize, 'Th2', cells, in, the, presence, of, 'IL-12;', and, '(', 'c)', 'OX40L', exacerbated, 'IL-12-induced', 'Th1', cell, inflammation, by, promoting, 'TNF-alpha,', while, inhibiting, 'IL-10'])]). relacion([sujeto(['We', conclude, that, 'OX40L', on, 'TSLP-activated', 'DCs']), verbo([triggers]), complemento(['Th2', cell, polarization, in, the, absence, of, 'IL-12,', and, propose, that, 'OX40L', can, switch, 'IL-10-producing', regulatory, 'Th', cell, responses, into, 'TNF-alpha-producing', inflammatory, 'Th', cell, responses])]). relacion([sujeto(['GATA-3', was, shown, to]), verbo([bind]), complemento([to, two, sites, of, the, 'IL-4', gene, promoter, in, human, 'T-cell', lines, 'PER-117', and, 'Jurkat'])]). relacion([sujeto(['A', motif, located, in, the, region, of, position, -, 860, and, responsible, for, 'GATA-3']), verbo([binding]), complemento([was, detected, for, the, first, time])]). relacion([sujeto(['Mutation', or, deletion, of, this, site]), verbo([increased]), complemento([the, promoter, activity])]). relacion([sujeto(['The', findings]), verbo([suggest]), complemento([a, direct, involvement, of, 'GATA-3', in, regulation, of, the, human, 'IL-4', gene, transcription, as, a, repressor, of, the, promoter, activity])]). relacion([sujeto(['We', also, show, that, a, genetic, interaction, between, 'T-bet', and, its]), verbo([target]), complemento(['Hlx', seems, to, be, required, for, 'Th1', 'maturation,', but, that, 'Hlx', may, also, be, dispensable, for, maintenance, of, a, transcriptionally, permissive, ifng, gene])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, signature, gene, activity, of, helper, 'T', cells, is, initially, plastic, but, later, becomes, epigenetically, fixed, and, offer, an, initial, strategy, for, inducing, mature, cells, to, switch, their, fate])]). relacion([sujeto(['The', effects, of, 17, 'beta-estradiol', '(', 'E2)', on, immune, function]), verbo([have]), complemento([been, extensively, reported])]). relacion([sujeto(['Through', the, use, of, 'ER-deficient', 'mice,', we, and, others]), verbo([have]), complemento([begun, to, demonstrate, the, role, of, the, two, known, receptors, in, modulating, immune, functional, activities])]). relacion([sujeto(['Previous', studies]), verbo([have]), complemento([shown, that, cells, of, the, innate, immune, system, have, altered, function, '(', bactericidal, 'capacity)', and, patterns, of, cytokine, expression, '(', increased, proinflammatory, cytokine, 'expression)', through, amelioration, of, 'ERalpha', signaling])]). relacion([sujeto(['Our', results, demonstrate, that, 'ERalpha', deficiency, in, splenic, 'macrophages,', but, not, 'CD11c+', splenic, dendritic, cells, pulsed, with, 'OVA', significantly]), verbo([enhances]), complemento([proliferative, responses, and, 'IFN-gamma', production, by, transgenic, 'OVA', 'peptide-specific', '(', 'OT-II)', 'CD4+', 'T', cells, when, compared, with, 'Ag-pulsed', 'APC', from, 'wild-type', littermates])]). relacion([sujeto(['In', 'addition,', when, purified, 'CD4+', 'T', cells, from, 'ERalpha-deficient', and, 'wild-type', littermates, were]), verbo([stimulated]), complemento([with, 'anti-CD3/CD28', 'Ab', in, the, absence, of, 'E2,', there, were, no, significant, differences, in, 'IFN-gamma', or, 'IL-4', production])]). relacion([sujeto(['However,', the, addition, of, 'E2', significantly]), verbo([increased]), complemento(['IL-4', 'secretion,', as, well, as, increased, 'GATA-3', mRNA, levels, from, 'ERalpha-replete', 'CD4+', 'T', 'cells,', while, this, effect, was, abrogated, in, 'ERalpha-deficient', 'CD4+', 'T', cells])]). relacion([sujeto(['We']), verbo([have]), complemento([shown, that, 'LLO', facilitates, development, of, 'T', cells, mediating, protective, immunity, against, 'L'])]). relacion([sujeto(['Based', on, this, 'finding,', it, is, postulated, that, 'LLO']), verbo([inhibits]), complemento([differentiation, of, 'Th2', cells, and, the, 'Th2', immune, response])]). relacion([sujeto(['By', using, a, murine, model, of, ovalbumin, '(', 'OVA)-induced', allergic, 'rhinitis,', we, investigated, whether, 'LLO']), verbo([has]), complemento([an, ability, to, modulate, the, 'Th2-type', immune, disorder])]). relacion([sujeto(['However,', 'LLO', treatment, during, sensitization, markedly]), verbo([inhibited]), complemento([the, eosinophil, infiltration, and, production, of, these, 'anti-OVA', antibodies])]). relacion([sujeto(['In', 'contrast,', 'OVA-specific', 'IFN-gamma-producing', 'T', cells, were, preferentially]), verbo([induced]), complemento([in, mice, treated, with, 'LLO', at, the, time, of, sensitization])]). relacion([sujeto(['In', the, absence, of, 'LLO', 'administration,', the, expression, level, of, 'GATA-3', and, 'SOCS-3', in, 'CD4(+)', 'T', cells, was]), verbo([enhanced]), complemento([after, sensitization, with, 'OVA'])]). relacion([sujeto(['LLO', treatment, resulted, in, a, reduction, of, 'GATA-3', and, 'SOCS-3', expressions, but]), verbo([induced]), complemento([the, transcription, of, 'T-bet', instead])]). relacion([sujeto(['Taken', 'together,', these, data, show, clearly, that, 'LLO', is, capable, of]), verbo([inhibiting]), complemento(['Th2', immune, response, by, skewing, differentiation, of, 'antigen-specific', 'T', cells, into, 'Th1', cells])]). relacion([sujeto(['T-bet', is, an, important, 'Th1', driving, transcription, factor]), verbo([regulated]), complemento([by, 'IFN-gamma/STAT1', pathway])]). relacion([sujeto(['Previous']), verbo([reports]), complemento([have, characterized, function, of, 'T-bet', mainly, in, murine, cells, and, very, little, is, known, about, its, functions, in, human, cells])]). relacion([sujeto(['We', demonstrate, that, in, addition, to, 'CD3/CD28', 'activation,', cytokines, 'IL-12', and, 'IFN-alpha', in, the, presence, of, neutralizing, 'anti-IFN-gamma']), verbo([enhanced]), complemento(['T-bet', mRNA, and, protein, expression, in, human, 'CD4+', cells])]). relacion([sujeto(['Even', though, 'IFN-gamma', and, 'IL-12', stimulation]), verbo([induced]), complemento([similar, levels, of, 'T-bet', protein, in, human, 'CD4+', 'cells,', 'IFN-gamma-treated', cells, produced, considerably, less, 'IFN-gamma', than, cells, treated, with, 'IL-12'])]). relacion([sujeto(['In', 'addition,', we, show, that, the, immunosuppressive, cytokine, 'TGF-beta']), verbo([inhibits]), complemento(['T-bet', and, 'GATA3', protein, expression, only, if, it, is, present, prior, to, primary, 'T', cell, activation, and, is, maintained, in, the, cultures, during, the, early, polarization, of, 'Th1/Th2', cells])]). relacion([sujeto(['In', 'conclusion,', we]), verbo([report]), complemento([new, insights, into, the, cytokine, regulation, of, 'T-bet', in, human, 'CD4+', 'T', cells])]). relacion([sujeto(['The', differentiation, of, naïve, 'T', helper, '(', 'Th)', cells, is]), verbo([induced]), complemento([by, 'TCR', activation, and, 'IL-12/STAT4', or, 'IL-4/STAT6', signaling, 'pathways,', forming, 'Th1', and, 'Th2', 'cells,', respectively])]). relacion([sujeto(['In', this, 'study,', oligonucleotide, arrays, were, used, to, identify, genes]), verbo([regulated]), complemento([during, the, initiation, of, human, 'Th1', and, 'Th2', cell, differentiation, at, 2, and, 6, h, in, presence, or, absence, of, immunosuppressive, 'TGF-beta'])]). relacion([sujeto(['As', a, result, the, immediate]), verbo([targets]), complemento([of, 'IL-12,', 'IL-4', and, 'TGF-beta', were, identified])]). relacion([sujeto(['IL-4,', 'however,', was, observed, to, rapidly]), verbo([regulate]), complemento([63, 'genes,', 26, of, which, were, differentially, expressed, at, both, the, 2, -, and, 6, -, h, time, points])]). relacion([sujeto(['Of', these, 'IL-4']), verbo([regulated]), complemento(['genes,', 'one-third', have, previously, been, observed, to, display, expression, changes, in, the, later, phases, of, the, polarization, process])]). relacion([sujeto(['Similarly', to, the, key, 'regulators,', 'TBX21', and, 'GATA3,', the, transcription, factors, 'SATB1,', 'TCF7', and, 'BCL6', were, differentially]), verbo([regulated]), complemento([at, the, protein, level, during, early, 'Th1', and, 'Th2', cell, polarization])]). relacion([sujeto(['Type', 2, cytokines, are, usually, predominant, in, tumor, patients, and]), verbo([associated]), complemento([with, tumor, progression])]). relacion([sujeto(['Tetra-Methylpyrazine', '(', 'TTMP),', extracted, from, a, traditional, 'Chinese', medicinal, herb, which]), verbo([has]), complemento([been, used, in, clinic, to, reverse, the, 'Th2', status, of, cancer, patients, in, 'China,', was, added, to, 'PBMC', culture])]). relacion([sujeto(['The', potential, of, gene]), verbo([expressing]), complemento(['(', measured, as, relative, intensity, to, the, ratio, of, 'beta-actin)', in, the, patients, for, type, 1, cytokines, was, also, in, a, low, level, '(', 0.111, for, 'IFN-gamma,', 0.119, for, 'IL-2)', in, comparison, with, a, relative, high, level, for, type, 2, cytokines, '(', 0.319, for, 'IL-4,', 0.303, for, 'IL-6', and, 0.377, for, 'IL-10)'])]). relacion([sujeto(['TTMP', could]), verbo([enhance]), complemento([supernatant, concentration, and, gene, expression, levels, of, 'IFN-gamma,', 'IL-2', and, 'T-bet,', but, reduce, those, of, type, 2, cytokines])]). relacion([sujeto(['Previous', studies]), verbo([have]), complemento([shown, that, tumor, cells, predominantly, express, 'Th2', type, cytokines, and, transcription, factors])]). relacion([sujeto(['So', whether, the, expression, of, 'GATA-3', in, tumor, cells]), verbo([has]), complemento([any, effect, on, tumor, development, is, a, question, of, interest])]). relacion([sujeto(['In', the, present, 'study,', we]), verbo([inhibited]), complemento([the, expression, of, 'GATA-3', in, tumor, cells, through, antisense, 'RNA', blockade, 'technique,', and, observed, its, effects, on, tumor, in, vitro, and, in, vivo])]). relacion([sujeto(['Our', results, showed, that, antisense, 'GATA-3', treatment, could]), verbo([inhibit]), complemento([the, expression, of, 'TNF-alpha', and, 'Th2', cytokines, in, tumor, 'cells,', and, 'antisense-induced', blockade, of, 'GATA-3', could, also, depress, tumor, growth, in, 'tumor-bearing', mice])]). relacion([sujeto(['We']), verbo([suggest]), complemento([that, the, ratio, of, 'T-bet/GATA-3', can, be, evaluated, as, a, more, important, marker, of, the, status, of, 'Th1/Th2', type])]). relacion([sujeto(['And', our, results, might]), verbo([provide]), complemento([some, evidence, about, the, molecular, regulatory, mechanisms, in, tumor, cell, development])]). relacion([sujeto(['We']), verbo([found]), complemento([a, substantial, genetic, contribution, to, the, production, of, 'Th1', cytokines, such, as, 'IFN-gamma', and, 'TNF-alpha', with, heritabilities, of, 0.85, '(', 95, '%', confidence, 'intervals,', 0.74, -, 0.95, ')', and, 0.72, '(', 0.5, -, 0.93, ')', ',', 'respectively,', whereas, no, genetic, influence, on, production, of, the, 'Th2', signature, cytokine, 'IL-4', was, observed])]). relacion([sujeto(['Our', data]), verbo([provide]), complemento([novel, insights, into, the, genetic, regulation, of, human, 'Th', cell, polarization])]). relacion([sujeto(['These', data]), verbo([suggest]), complemento([that, signature, cytokines, and, cytokine, signaling, events, of, 'Th1', rather, than, 'Th2', cells, are, genetically, determined, and, implicate, that, 'Th2-associated', diseases, in, humans, might, be, due, to, genetic, variations, in, 'Th1', cytokine, regulation, via, 'T-bet'])]). relacion([sujeto(['This', concept, is, highlighted, by, the, recent]), verbo([finding]), complemento([that, inactivation, of, the, 'T-bet', gene, in, mice, results, in, development, of, clinical, hallmark, features, of, asthma])]). relacion([sujeto(['GILZ', '(', 'glucocorticoid-induced', leucine, 'zipper),', a, gene]), verbo([induced]), complemento([by, 'dexamethasone,', is, involved, in, control, of, 'T', lymphocyte, activation, and, apoptosis])]). relacion([sujeto(['Up-regulation', correlated, with]), verbo([increased]), complemento([expression, of, 'GATA-3', and, signal, transducer, and, activator, of, transcription, 6, '(', 'Stat6),', 'Th-2-specific', transcription, factors, and, decreased, expression, of, 'T-bet,', a, transcription, factor, involved, in, 'Th-1', differentiation])]). relacion([sujeto(['Finally,', in, 'TG', mice, 'delayed-type', 'hypersensitivity,', a, 'Th-1', 'response,', was]), verbo([inhibited]), complemento([and, 'bleomycin-induced', pulmonary, 'fibrosis,', a, 'Th-2', mediated, 'disease,', was, more, severe])]). relacion([sujeto(['These', results, indicate, that, 'Gilz', contributes, to, 'CD4+', commitment, toward, a, 'Th-2', phenotype, and]), verbo([suggest]), complemento([this, contribution, may, be, another, mechanism, accounting, for, glucocorticoid, immunomodulation])]). relacion([sujeto(['Allitridin']), verbo([induced]), complemento([significantly, '(', 'P', &, 'lt;'])]). relacion([sujeto([1, ')']), verbo([increased]), complemento([expression, of, the, transcription, factor, 'T-bet', and, the, 'Th1', cytokine, 'IFN-gamma', and, markedly, '(', 'P', &, 'lt;'])]). relacion([sujeto([1, ')']), verbo([decreased]), complemento([expression, of, the, transcription, factor, 'GATA-3', and, the, 'Th2', cytokine, 'IL-10'])]). relacion([sujeto(['Thus', 'MCMV', infection, could]), verbo([lead]), complemento([to, disequilibrium, of, 'Th1/Th2', cytokine, 'expression:', 'The', level, of, the, 'Th1', cytokine, 'IFN-gamma', was, decreased, 'significantly,', and, 'Th2', cytokine, 'IL-10', was, overexpressed, markedly])]). relacion([sujeto(['Allitridin', could, 'up-regulate', the, expression, of, 'T-bet', and, 'IFN-gamma', and]), verbo([inhibit]), complemento([the, expression, of, 'GATA-3', and, 'IL-10', in, 'MCMV-infected', 'mice,', indicating, a, 'Th1', dominant, 'state,', which, should, enhance, the, specific, cellular, immune, reactions, against, cytomegalovirus, '(', 'CMV)', and, be, helpful, for, clearance, of, 'CMV', from, the, host])]). relacion([sujeto(['Here,', we]), verbo([provide]), complemento([evidence, that, early, 'IL-4', production, by, naive, 'CD4+', 'T', cells, stimulated, with, cognate, peptide, requires, 'TCR-induced', early, 'GATA-3', expression, and, 'IL-2', receptor, 'signaling,', both, of, which, are, controlled, by, the, degree, of, activation, of, extracellular, 'signal-regulated', kinase, '(', 'ERK)'])]). relacion([sujeto(['To', investigate, effects, of, 'CpG', oligodeoxynucleotide, '(', 'CpG', 'ODN)', on, the, mRNA, expression, of, transcription, factors, 'GATA']), verbo([binding]), complemento([protein, 3, '(', 'GATA-3)', and, 'T-box', expressed, in, 'T', cells, '(', 'T-bet)', in, asthmatic, mice])]). relacion([sujeto(['CpG', 'ODN', treatment]), verbo([increased]), complemento([the, 'interferon-gamma', concentration, but, decreased, the, 'interleukin-4', concentration, in, both, 'BALF', and, splenocyte, culture, supernatants])]). relacion([sujeto(['CpG', 'ODN', treatment]), verbo([inhibits]), complemento([airway, inflammatory, cell, infiltration, and, regulates, 'interferon-gamma/interleukin-4', synthesis, in, asthmatic, 'mice,', possibly, through, a, mechanism, of, downregulation, of, 'GATA-3', mRNA, expression, in, both, lung, tissue, and, splenocytes])]). relacion([sujeto(['We', previously, showed, that, a, positive, impact, of, peritoneal, defense, response, on, the, outcome, of, peritoneal, dialysis, '(', 'PD)-related', peritonitis, is, characterized, by, an]), verbo([increased]), complemento([pattern, of, peritoneal, 'CD4/CD8', 'T-cell', ratio, with, a, predominant, 'CD4(+)-T', helper, subtype, 1, phenotype])]). relacion([sujeto(['To', further, explore, longitudinal, changes, in, peritoneal, immunity, during, 'PD-related', 'peritonitis,', we, examined, the, production, of, interleukin, 12, '(', 'IL-12),', 'IL-18,', and, interferon, gamma, '(', 'IFN-gamma)', in, peritoneal, dialysate, effluent, '(', 'PDE)', and, kinetic, expression, of, the, transcription, factors, 'T', box]), verbo([expressed]), complemento([in, 'T', cells, '(', 'T-bet)', and, guanine, adenine, thymine, adenine, '(', 'GATA)', binding, protein, 3, '(', 'GATA-3)', in, peritoneal, 'T', cells, during, peritonitis])]). relacion([sujeto(['In', the, 'rapid-response', 'group,', 'IFN-gamma', and, 'T-bet', mRNA, expression, 'increased,', whereas, that, of, 'GATA-3']), verbo([decreased]), complemento([over, time])]). relacion([sujeto(['Results', were, opposite, in, the, 'delayed-response', 'group,', with, 'IFN-gamma', and, 'T-bet', levels]), verbo([decreasing]), complemento([and, 'GATA-3', levels, increasing, over, time])]). relacion([sujeto(['These', data]), verbo([suggest]), complemento([that, local, 'IL-12', and, 'IL-18', production, is, part, of, a, protective, early, immune, response, to, 'PD-related', peritonitis])]). relacion([sujeto(['Indeed,', the, 'CYP19', gene, encoding, 'P450', 'aromatase,', the, key, enzyme, for, estrogen, 'biosynthesis,', is, 'up-regulated', in, breast, tumors, predominantly, via, the, 'cAMP-responsive', 'gonad-type', 'PII', 'promoter,', ultimately]), verbo([leading]), complemento([to, increased, intratumoral, estrogen, production, and, tumor, growth])]). relacion([sujeto(['Thus,', identifying, the, molecular, factors]), verbo([involved]), complemento([in, aromatase, 'PII', promoter, regulation, is, essential, for, our, understanding, and, treatment, of, the, disease])]). relacion([sujeto(['Because', we]), verbo([have]), complemento([previously, shown, activity, of, the, murine, aromatase, 'PII', promoter, to, be, markedly, 'up-regulated', by, 'GATA', factors, with, respect, to, the, 'gonads,', we, hypothesized, that, 'GATA', factors, are, also, key, determinants, of, human, 'PII', 'promoter-driven', aromatase, transcription, in, breast, tumors])]). relacion([sujeto(['We', now, show, that, 'GATA3', and, 'GATA4', are, indeed]), verbo([expressed]), complemento([in, several, breast, cancer, cells, lines])]). relacion([sujeto(['Consistent', with, the, cAMP, dependence, of, the, 'PII', 'promoter,', activation, elicited, by, 'GATA3', or, 'GATA4', alone, and, the, striking, synergism, between, 'GATA3', or, 'GATA4', and, the]), verbo([nuclear]), complemento([receptor, liver, receptor, homolog, '(', 'LRH)-1', was, intimately, linked, to, forskolin, treatment, or, overexpression, of, protein, kinase, 'A', '(', 'PKA)', catalytic, subunit])]). relacion([sujeto(['PKA-mediated', phosphorylation]), verbo([increases]), complemento([the, interaction, between, 'GATA3', and, 'LRH-1', and, the, requirement, for, 'PKA', in, aromatase, 'PII', promoter, stimulation, involves, at, least, three, specific, amino, acid, 'residues:', 'GATA3', 'Ser308,', 'GATA4', 'Ser261,', and, 'LRH-1', 'Ser469'])]). relacion([sujeto(['Finally,', we, show, that, the, human, 'LRH-1', promoter, is, itself, a]), verbo([target]), complemento([for, 'GATA', factors])]). relacion([sujeto(['Thus,', taken, 'together,', our, results]), verbo([suggest]), complemento([that, 'GATA', factors, likely, contribute, to, aberrant, aromatase, expression, in, breast, tumors, through, two, 'distinct,', yet, complementary, mechanisms])]). relacion([sujeto(['Here,', we]), verbo([have]), complemento([characterized, live, 'IFN-gamma+,', 'IL-4+', and, 'IFN-gamma-/IL-4-', cells, isolated, from, 'Th', cell, cultures, treated, under, 'Th1', or, 'Th2', polarizing, conditions, by, employing, affinity, matrix, capture, technology])]). relacion([sujeto(['The', double, negative, cells, from, either, 'Th1', or, 'Th2', cultures]), verbo([expressed]), complemento([lower, levels, of, 'Th1/Th2', marker, cytokine, genes, '(', 'IFNgamma,', 'IL4,', and, 'IL5)'])]). relacion([sujeto(['Gene', expression, profiling, analysis, showed, that, very, few, previously, identified, 'Th1/Th2', marker, genes, were, differentially]), verbo([expressed]), complemento([between, the, 'IFN-gamma', or, 'IL-4', producers, and, the, 'non-producers,', further, underscoring, the, similarity, between, these, two, groups])]). relacion([sujeto(['My', colleagues, and, 'I']), verbo([have]), complemento([studied, the, contributions, of, these, processes, to, differentiation, of, naïve, 'CD4+', 'T-cells', to, either, a, 'Th1', or, 'Th2', phenotype])]). relacion([sujeto(['Our', initial, discovery, that, pathogens, in, our, in, vitro, priming, system]), verbo([led]), complemento([to, the, development, of, 'Th1', cells, through, the, action, of, 'interleukin-12', was, important, evidence, of, a, link, between, innate, and, adaptive, immunity])]). relacion([sujeto(['Other', interesting, projects, that]), verbo([have]), complemento([emerged, as, a, result, of, our, 'Th', cell, differentiation, studies, include, understanding, the, role, of, the, inhibitory, immunoreceptor, 'B-', and, 'T-lymphocyte', attenuator, in, the, immune, 'response,', as, well, as, the, role, of, the, transcription, factor, 'ERM', in, both, 'T-cells', and, spermatogenesis])]). relacion([sujeto(['We', currently]), verbo([maintain]), complemento([our, interests, in, the, 'Th', differentiation, field, by, trying, to, understand, the, role, of, type, 1, interferons, in, 'Th1', development, and, the, role, of, alternate, promoters, for, the, 'GATA-3', 'gene,', among, other, 'things,', but, are, also, actively, embarking, on, studies, related, to, the, choice, between, divergent, cell, types, during, embryonic, stem, cell, differentiation])]). relacion([sujeto(['However,', the, molecular, mechanisms, of, 'CCR5', regulation, in, primary]), verbo([targets]), complemento([of, 'HIV-1', remain, unknown])]). relacion([sujeto(['Despite']), verbo([binding]), complemento([to, conserved, 'DNA', 'elements,', we, show, that, the, transcription, factors, 'GATA', binding, protein, 1, '(', 'GATA-1)', and, 'GATA-3', differentially, suppress, the, expression, of, 'CCR5', in, 'stem-cell-derived', dendritic, cells, and, primary, human, 'T-cell', subsets])]). relacion([sujeto(['In', 'addition,', 'GATA-1', expression, was, also, more, potent, than, 'GATA-3', in]), verbo([suppressing]), complemento(['T', helper, 1, '(', 'Th1)-associated', 'genes,', 'interferon-gamma', '(', 'IFNgamma),', and, 'CXC', chemokine, 'receptor-3', '(', 'CXCR3)'])]). relacion([sujeto(['GATA-1,', but, not, 'GATA-3,', potently]), verbo([suppressed]), complemento(['CCR5', 'transcription,', thereby, rendering, human, 'T', cells, resistant, to, 'CCR5-tropic', 'HIV-1', infection])]). relacion([sujeto(['These', findings]), verbo([provide]), complemento([insight, into, 'GATA-3-mediated', gene, regulation, during, 'T-cell', differentiation])]). relacion([sujeto(['Importantly,', decoding, the, mechanisms, of, 'GATA-1-mediated', repression, of, 'CCR5', may, offer, an, opportunity, to, develop, novel, approaches, to]), verbo([inhibit]), complemento(['CCR5', expression, in, 'T', cells])]). relacion([sujeto(['Gata-3']), verbo([has]), complemento([been, shown, to, specifically, alter, its, expression, patterns, in, different, types, of, cancers])]). relacion([sujeto(['Recent', evidence]), verbo([suggests]), complemento([that, an, interference, of, 'Gata-3', exists, in, the, 'TGF-beta', signaling, pathway])]). relacion([sujeto(['In', an, electrophoretic, mobility, shift, 'assay,', a, disturbed]), verbo([nuclear]), complemento([translocation, was, confirmed])]). relacion([sujeto(['Furthermore,', strong, specific, upregulation, of, 'Gata-3', impaired]), verbo([nuclear]), complemento([translocation, and, its, cooperative, action, with, the, 'TGF-beta', 'pathway,', suggesting, that, 'Gata-3', plays, a, central, role, in, human, pancreatic, cancer])]). relacion([sujeto(['Functionally,', the, 'ORS']), verbo([has]), complemento([been, implicated, in, the, migration, of, hair, stem, cells, from, the, stem, cell, niche, toward, the, hair, bulb])]). relacion([sujeto(['However,', factors]), verbo([required]), complemento([for, the, differentiation, of, this, critical, cell, lineage, remain, to, be, identified])]). relacion([sujeto(['We', conclude, that, although, 'Sox9', is, dispensable, for, hair, 'induction,', it, directs, differentiation, of, the, 'ORS', and, is]), verbo([required]), complemento([for, the, formation, of, the, hair, stem, cell, compartment])]). relacion([sujeto(['Our', genetic, analysis, places, 'Sox9', in, a, molecular, cascade, downstream, of, sonic, hedgehog, and]), verbo([suggests]), complemento([that, this, gene, is, involved, in, basal, cell, carcinoma])]). relacion([sujeto(['The', consequences, that, drug, withdrawal]), verbo([has]), complemento([on, immune, functioning, has, only, recently, been, 'appreciated;', 'however,', given, the, wide, variety, of, use, and, abuse, of, opiate, 'analgesics,', understanding, the, decrements, to, immune, function, that, withdrawal, from, these, drugs, causes, is, of, crucial, importance])]). relacion([sujeto(['In', previous, 'work,', we]), verbo([have]), complemento([demonstrated, that, morphine, treatment, contributes, to, immunosuppression, by, polarizing, 'Th', cells, toward, the, 'Th2', lineage])]). relacion([sujeto(['It', was, determined, that, 24, -, h, morphine, withdrawal, resulted, in, a]), verbo([decrease]), complemento([in, 'IFN-gamma,', the, 'Th1', signature, 'cytokine,', whereas, the, 'Th2', 'cytokine,', 'IL-4,', was, increased])]). relacion([sujeto(['In', 'addition,', 'Western', blot, and, 'EMSA', experiments, revealed, that, morphine, 'withdrawal-induced', 'Th2', differentiation, was]), verbo([mediated]), complemento([through, the, classical, 'Th2', transcription, factors, 'Stat-6', and, 'GATA-3'])]). relacion([sujeto(['Following', 'withdrawal,', it, was]), verbo([found]), complemento([that, the, 'Th1-polarizing', cytokine, 'IL-12', was, significantly, 'decreased,', providing, further, support, for, the, observation, that, withdrawal, results, in, 'Th2', differentiation, by, possibly, impacting, the, generation, of, an, appropriate, innate, immune, response, which, directs, subsequent, adaptive, 'Th1/Th2', responses])]). relacion([sujeto(['CD4+', 'T', cells, with, a, block, in, the, 'NF-kappaB', signaling, pathway, exhibit]), verbo([decreases]), complemento([in, 'Th1', responses, and, diminished, nuclear, levels, of, multiple, transactivating, 'NF-kappaB/Rel/IkappaB', proteins])]). relacion([sujeto(['To', determine, the, 'lineage-intrinsic', contributions, of, these, transactivators, to, 'Th', 'differentiation,', 'T', cells, from, mice, deficient, in, specific, subunits, were, cultured, in, exogenous, cytokines]), verbo([promoting]), complemento([either, 'Th1', or, 'Th2', differentiation])]). relacion([sujeto(['The', absence, of, 'RelB']), verbo([led]), complemento([to, a, dramatic, decrease, in, the, expression, of, 'T-box', expressed, in, 'T', cells, and, 'Stat4'])]). relacion([sujeto(['In', 'contrast,', 'Bcl-3-deficient', cells, exhibited]), verbo([decreased]), complemento(['GATA-3,', consistent, with, evidence, that, 'Bcl-3', can, transactivate, a, gata3, promoter])]). relacion([sujeto(['These', data, indicate, that, 'Bcl-3', and, 'RelB', exert, distinct, and, opposing, effects, on, the, expression, of, 'subset-determining', transcription, 'factors,']), verbo([suggesting]), complemento([that, the, characteristics, of, 'Th', cell, responses, may, be, regulated, by, titrating, the, stoichiometry, of, transactivating, 'NF-kappaB/Rel/IkappaB', complexes, in, the, nuclei, of, developing, helper, effector, cells])]). relacion([sujeto(['It']), verbo([expresses]), complemento([numerous, molecular, markers, characteristic, of, auditory, 'neuroblasts,', including, the, transcription, factors, 'GATA3,', 'NeuroD,', 'Brn3a', and, 'Islet1,', as, well, as, the, neuronal, cytoskeletal, protein, 'beta3-tubulin'])]). relacion([sujeto(['Cells', that]), verbo([found]), complemento([their, way, into, the, retinal, ganglion, cell, layer, extended, multiple, processes, but, did, not, express, 'beta3-tubulin'])]). relacion([sujeto(['The', ability, of, 'N33', to, 'migrate,', to, 'differentiate,', to, localize, with, native, 'SGNs', in, vitro, and, to, survive, in, vivo]), verbo([suggests]), complemento([that, they, provide, an, effective, model, for, 'SGN', differentiation, and, for, cell, transplantation, into, the, ear])]). relacion([sujeto(['However,', few, in, vivo, experiments]), verbo([have]), complemento([examined, the, function, of, 'GATA-3', in, 'Th1', and, 'Th2', immune, responses])]). relacion([sujeto(['Numbers', of, peripheral, blood, eosinophils, in, all, 'GATA-3-Tg', mice]), verbo([increased]), complemento([10, -, to, 20, -, fold, after, primary, infection, with, 'N'])]). relacion([sujeto(['Mice', immunized, with, 'PPD', were, intradermally, challenged, with, 'PPD', to]), verbo([induce]), complemento([delayed, type, hypersensitivity, '(', 'DTH)'])]). relacion([sujeto(['The', amount, of, footpad, swelling]), verbo([caused]), complemento([by, the, 'DTH', reaction, in, 'GATA-3-Tg', mice, was, significantly, smaller, than, that, of, control, littermates])]). relacion([sujeto(['Inguinal', lymph, node, cells, from, 'GATA-3-Tg', mice]), verbo([stimulated]), complemento([with, 'PPD', in, vitro, secreted, more, 'IL-5,', 'IL-10', and, less, 'IFN-gamma', than, those, of, control, littermates])]). relacion([sujeto(['These', results]), verbo([suggested]), complemento([that, 'Th1', and, 'Th2', driven, conditions, enhance, 'IL-5', production, in, 'GATA-3-Tg', mice, through, the, direct, binding, of, 'GATA-3', to, the, 'IL-5', promoter, region])]). relacion([sujeto(['The', influence, of, 'GATA-3', on, 'IL-13,', 'IFN-gamma', and, 'IL-10', production, varied, according, to, the]), verbo([stimulating]), complemento([conditions])]). relacion([sujeto(['However,', 'IL-4', production, was, not, significantly, elevated, in, 'GATA-3-Tg', 'mice,', indicating, that, 'IL-4', and, 'IL-5', production, was, differentially]), verbo([regulated]), complemento([in, these, mice])]). relacion([sujeto(['The', expression, ratio, of, 'T-bet', :, 'Gata3,', master, transcription, factors, for, 'Th1', and, 'Th2', 'cytokines,', was]), verbo([increased]), complemento([in, the, 'MLN', from, 'NTP-2000-fed', 'BBdp', rats, compared, with, that, from, 'BBc', 'rats,', mainly, due, to, decreased, 'Gata3', expression])]). relacion([sujeto(['This', proliferation, was]), verbo([associated]), complemento([with, a, low, proportion, of, 'CD4(+)CD25(+)', 'T', cells, and, a, high, proportion, of, dendritic, cells, in, the, 'MLN', of, 'BBdp', rats])]). relacion([sujeto(['Adult', idiopathic, thrombocytopenic, purpura, '(', 'ITP)', is, a, chronic, acquired, 'organ-specific', autoimmune, hemorrhagic, disease, characterized, by, the, production, of, antibodies, against, antigens, on, the, membranes, of, 'platelet,', resulting, in]), verbo([enhanced]), complemento(['Fc-mediated', destruction, of, the, platelets, by, macrophages, in, the, reticuloendothelial, system])]). relacion([sujeto(['The', balance, of, 'Th1/Th2', and, 'Tc1/Tc2', was, studied, by, simultaneous, analysis, of, intracellular, cytokines, of, peripheral, blood, mononuclear, cells, and, splenocytes, in, 'short-term', cultures]), verbo([activated]), complemento([with, 'PMA/ionomycin', as, well, as, mRNA, expression, of, 'T-bet', and, 'GATA-3', in, peripheral, blood, mononuclear, cells, and, splenocytes, using, 'real-time', polymerase, chain, reaction])]). relacion([sujeto(['The', 'T-bet/GATA-3', ratio, may]), verbo([provide]), complemento([a, surrogate, marker, of, 'T1/T2', cytokine, balance])]). relacion([sujeto(['Human', 'HDR', '(', 'hypoparathyroidism,', deafness, and, renal, 'dysplasia)-syndrome', is]), verbo([caused]), complemento([by, haploinsufficiency, of, 'zinc-finger', transcription, factor, 'GATA3'])]). relacion([sujeto(['The', hearing]), verbo([loss]), complemento([due, to, 'GATA3', haploinsufficiency, has, been, shown, to, be, peripheral, in, 'origin,', but, it, is, unclear, to, what, extent, potential, aberrations, in, the, outer, hair, cells, '(', 'OHCs)', contribute, to, this, disorder])]). relacion([sujeto(['While', the, 'signal-to-noise', ratios, of, distortion, product, otoacoustic, emissions, '(', 'DPOAE)', in, wild, type, mice, did, not, change, significantly, during, the, first, 'half-year', of, 'live,', those, in, the, heterozygous, 'Gata3', mice]), verbo([decreased]), complemento([dramatically])]). relacion([sujeto(['In', 'addition,', both, light, microscopic, and, transmission, electron, microscopic, analyses, showed, that, the, number, of, 'OHCs', containing, vacuoles, was]), verbo([increased]), complemento([in, the, mutants])]). relacion([sujeto(['Together,', these, findings, indicate, that, outer, hair, cell, malfunctioning, plays, a, major, role, in, the, hearing]), verbo([loss]), complemento([in, 'HDR-syndrome'])]). relacion([sujeto(['T-bet', and, 'GATA-3', transcription, factors]), verbo([associated]), complemento([with, 'Th1', and, 'Th2', responses, 'respectively,', and, 'IFNgamma', and, 'IL-4', mRNA, levels, were, measured, by, 'real-time', 'PCR'])]). relacion([sujeto(['In', 'conclusion,', 'RA', blood, cells, showed, a]), verbo([decreased]), complemento(['Th1', situation, as, indicated, by, low, 'IFNgamma', and, 'T-bet', mRNA, expression])]). relacion([sujeto(['This', pattern, was]), verbo([found]), complemento([only, in, patients, with, the, most, active, disease])]). relacion([sujeto(['Differentiation', of, naive, 'CD4', 'T', cells, into, 'Th2', cells]), verbo([requires]), complemento([protein, expression, of, 'GATA3'])]). relacion([sujeto(['Interleukin-4']), verbo([induces]), complemento(['STAT6', activation, and, subsequent, 'GATA3', transcription])]). relacion([sujeto(['Little', is, 'known,', 'however,', on, how, 'T', cell, 'receptor-mediated', signaling]), verbo([regulates]), complemento(['GATA3', and, 'Th2', cell, differentiation])]). relacion([sujeto(['Mdm2', was]), verbo([associated]), complemento([with, 'GATA3', and, induced, ubiquitination, on, 'GATA3,', suggesting, its, role, as, a, 'ubiquitin-protein', isopeptide, ligase, for, 'GATA3', ubiquitination])]). relacion([sujeto(['Thus,', the, 'Ras-ERK', 'MAPK', cascade, controls, 'GATA3', protein, stability, by, a, 'post-transcriptional', mechanism, and, facilitates, 'GATA3-mediated', chromatin, remodeling, at, 'Th2', cytokine, gene, loci]), verbo([leading]), complemento([to, successful, 'Th2', cell, differentiation])]). relacion([sujeto(['AMP-activated', protein, kinase, was]), verbo([reported]), complemento([recently, to, have, 'anti-inflammatory', activities, by, negatively, regulating, 'NF-kappaB', signaling])]). relacion([sujeto(['In', this, 'study,', we, investigated, the, prophylactic, and, therapeutic, efficacy, of, an, 'AMP-activated', protein, kinase, 'activator,', 5, -, 'aminoimidazole-4-carboxamide', ribonucleoside, '(', 'AICAR),', in, active, and, passive, 'EAE']), verbo([induced]), complemento([by, active, immunization, with, 'PLP(139-151)', or, 'MOG(35-55)', and, in, adoptive, transfer, of, 'PLP(139-151)-sensitized', 'T', 'cells,', respectively])]). relacion([sujeto(['The', 'anti-inflammatory', effects, of, 'AICAR', were]), verbo([associated]), complemento([with, the, inhibition, of, the, 'Ag-specific', recall, responses, and, inhibition, of, the, 'Th1-type', cytokines, 'IFN-gamma', and, 'TNF-alpha,', whereas, it, induced, the, production, of, 'Th2', cytokines, 'IL-4', and, 'IL-10'])]). relacion([sujeto(['Treatment', of, 'PLP(139-151)-specific', 'T', cells, in, vitro, with, 'AICAR']), verbo([decreased]), complemento([their, expression, of, 'T-bet', in, response, to, 'IL-12,', a, 'Th1', transcription, 'factor,', whereas, in, response, to, 'IL-4,', it, induced, the, expression, and, phosphorylation, of, 'Th2', transcription, factors, 'GATA3', and, 'STAT6,', respectively])]). relacion([sujeto(['Moreover,', treatment, of, 'APCs', in, vitro, with, 'AICAR']), verbo([inhibited]), complemento([their, capability, to, present, the, proteolipid, protein, peptide, to, 'PLP(139-151)-specific', 'T', cells])]). relacion([sujeto(['Primary', 'T', helper, 2, cells, are, 'heterogeneous,']), verbo([expressing]), complemento([subsets, of, cytokines, at, varying, levels])]). relacion([sujeto([1, is]), verbo([expressed]), complemento([in, 'Th2', but, not, 'Th1', cells])]). relacion([sujeto(['Th2', cytokine, production, is]), verbo([decreased]), complemento([in, cultures, transduced, with, a, 'PU'])]). relacion([sujeto([1, -]), verbo([expressing]), complemento([retrovirus, and, increased, in, 'Th2', cells, following, 'RNAi', that, decreases, 'PU'])]). relacion([sujeto([1, expression, is, restricted, to, a, subpopulation, of, 'Th2', cells, that]), verbo([express]), complemento(['CCL22', and, a, subset, of, 'Th2', cytokines])]). relacion([sujeto([1]), verbo([regulates]), complemento([the, 'Th2', phenotype, by, interfering, with, 'GATA-3', 'DNA', binding, without, altering, 'GATA-3', protein, levels])]). relacion([sujeto(['In', the, 'Th1', skewed, 'condition,', 'BV']), verbo([increased]), complemento([the, expression, of, 'IFN-gamma', mRNA, and, enhanced, the, expression, of, 'T-bet', on, purified, 'CD4(+)', 'T', cells, from, splenocytes, of, 'BALB/c', mice])]). relacion([sujeto(['It', significantly]), verbo([increased]), complemento([the, 'CD4(+)', 'T', cell, population, and, enhanced, 'IFN-gamma', 'expression,', while, 'IL-4', transcripts, were, not, altered, upon, in, vivo, activation, using, an, 'anti-CD3', antibody, injection])]). relacion([sujeto(['Taken', 'together,', these, results, imply, that, 'BV']), verbo([induces]), complemento(['Th1', lineage, development, from, 'CD4(+)', 'T', cells, by, increasing, the, expression, of, a, 'Th1-specific', 'cytokine,', 'IFN-gamma'])]). relacion([sujeto(['In', 'addition,', this, result, may, be]), verbo([mediated]), complemento([by, inducing, a, 'Th1-specific', transcription, 'factor,', 'T-bet'])]). relacion([sujeto(['We']), verbo([reported]), complemento([enhanced, 'IL-5', production, by, peripheral, blood, 'T', cells, of, asthmatic, patients])]). relacion([sujeto(['A', transcription, 'factor,', 'GATA-3,']), verbo([has]), complemento([been, implicated, in, 'IL-5', gene, expression])]). relacion([sujeto(['IL-5', promoter, activity, in, 'CD4+', 'T', cells, was]), verbo([enhanced]), complemento([by, overexpression, of, 'GATA-3,', whereas, it, was, diminished, by, the, introduction, of, mutations, in, the, putative, 'GATA-3', binding, sites])]). relacion([sujeto(['The', expression, level, of, 'GATA-3', may, not, be, an, essential, factor, to]), verbo([cause]), complemento(['IL-5', hyperproduction, in, bronchial, 'asthma,', though, 'GATA-3', is, crucially, involved, in, 'IL-5', gene, transcription, in, human, peripheral, 'CD4+', 'T', cells])]). relacion([sujeto(['Naive', 'T', helper, '(', 'Th)', lymphocytes, are]), verbo([induced]), complemento([to, express, the, il4, '(', 'interleukin-4)', gene, by, simultaneous, signaling, through, the, 'T', cell, receptor, and, the, interleukin, '(', 'IL)-4', receptor])]). relacion([sujeto(['This', memory, for, expression, of, the, il4, gene, depends, on, epigenetic, modification, of, the, il4, gene, locus, and, an]), verbo([increased]), complemento([expression, of, 'GATA-3,', the, key, transcription, factor, for, 'Th2', differentiation])]). relacion([sujeto(['Here,', we]), verbo([have]), complemento([identified, a, phylogenetically, conserved, 'sequence,', the, conserved, intronic, regulatory, 'element,', in, the, first, intron, of, the, il4, gene, containing, a, tandem, 'GATA-3', binding, site])]). relacion([sujeto(['We', show, that, 'GATA-3']), verbo([binds]), complemento([to, this, sequence, in, a, 'position-', and, 'orientation-dependent', 'manner,', in, vitro, and, in, vivo])]). relacion([sujeto(['Deletion', of, the]), verbo([conserved]), complemento([element, by, replacement, of, the, first, exon, and, part, of, the, first, intron, of, the, il4, gene, with, gfp, leads, to, a, defect, in, the, establishment, of, memory, for, expression, of, 'IL-4,', in, that, reexpression, of, 'IL-4', still, requires, costimulation, by, exogenous, 'IL-4'])]). relacion([sujeto(['The']), verbo([conserved]), complemento([intronic, regulatory, element, thus, links, the, initial, epigenetic, modification, of, the, il4, gene, to, 'GATA-3', and, serves, as, a, genetic, control, element, for, memory, expression, of, 'IL-4'])]). relacion([sujeto(['T-bet', '(', 'T-box']), verbo([expressed]), complemento([in, 'T', 'cells)', and, 'GATA-3', are, transcription, factors, that, play, a, critical, role, in, the, development, of, 'Th1', and, 'Th2', 'cells,', as, do, genes, of, the, 'SOCS', '(', suppressor, of, cytokine, 'signaling)', 'family,', albeit, indirectly])]). relacion([sujeto(['As', expected, '(', and, in, contrast, to, cells, of, uninfected, 'individuals),', there, was, a, significant, depression, of, gamma, interferon, '(', 'IFN-gamma)', and, a, concomitant]), verbo([increase]), complemento([in, 'interleukin-4', '(', 'IL-4),', 'IL-5,', and, 'IL-10', mRNA, expression, following, stimulation, with, parasite, antigen, '(', 'BmA)', but, not, with, a, polyclonal, 'T-cell', '(', 'anti-CD3)', stimulus])]). relacion([sujeto(['T-bet', '(', but, not, 'GATA-3)', was]), verbo([expressed]), complemento([at, significantly, lower, levels, in, cells, of, 'filaria-infected', individuals, in, response, to, 'BmA', compared, with, those, from, the, uninfected, 'group,', 'accounting,', at, least, 'partially,', for, the, diminished, 'IFN-gamma', expression])]). relacion([sujeto(['Second,', we]), verbo([found]), complemento([no, significant, differences, in, expression, of, 'Foxp3', between, the, two, 'groups,', although, induction, of, 'Foxp3', expression, correlated, with, induced, expression, levels, of, 'IL-10,', implicating, 'Tregs', in, the, 'IL-10', expression, seen])]). relacion([sujeto(['Our', data, therefore, indicate, that, the, impaired, 'Th1', responses, observed, in, patent, lymphatic, filariasis, are]), verbo([associated]), complemento([with, decreased, expression, of, 'T-bet,', 'SOCS-1,', 'SOCS-5,', and, 'SOCS-7', and, increased, expression, of, 'SOCS-3', in, 'T', cells])]). relacion([sujeto(['The', pathogenesis, of, allergic, asthma]), verbo([involves]), complemento([the, interplay, of, inflammatory, cells, and, resident, airway, 'cells,', and, of, their, secreted, mediators, including, 'cytokines,', 'chemokines,', growth, factors, and, inflammatory, mediators])]). relacion([sujeto(['Activation', of, tyrosine, kinases, invokes, multiple, downstream, signaling, 'pathways,', including, phosphoinositide, 3, -, kinase, '(', 'PI3K),', 'mitogen-activated', protein, kinase, '(', 'MAPK)', and]), verbo([nuclear]), complemento(['factor-kappaB', '(', 'NF-kappaB),', leading, to, cell, 'differentiation,', 'survival,', 'proliferation,', degranulation, and, chemotaxis])]). relacion([sujeto(['Inhibitors']), verbo([targeted]), complemento([at, different, enzyme, molecules, of, the, tyrosine, kinase, signaling, cascade, might, afford, therapeutic, potential, for, asthma])]). relacion([sujeto(['Anti-inflammatory', effects, of, pharmacological, agents]), verbo([targeted]), complemento([at, tyrosine, 'kinases,', 'Syk,', 'Itk,', signal, transducer, and, activator, of, 'transcription-1,', 'NF-kappaB,', 'GATA3,', 'EGFR,', 'PI3K,', 'MEK1/2,', p38, 'MAPK', and, 'JNK', have, been, reported, in, animal, models, of, allergic, airway, inflammation])]). relacion([sujeto(['Therefore,', development, of, inhibitors]), verbo([targeted]), complemento([at, the, tyrosine, kinase, signaling, cascade, is, an, attractive, strategy, for, the, treatment, of, asthma])]). relacion([sujeto(['The', type, 2, 'T-helper', '(', 'Th2)', lymphocyte, can, be, regarded, as, an, important]), verbo([target]), complemento([cell, for, the, treatment, of, allergic, asthma, as, it, plays, a, crucial, role, in, the, 'initiation,', progression, and, persistence, of, disease])]). relacion([sujeto(['Several', strategies, to]), verbo([target]), complemento(['Th2', cells, can, be, envisioned])]). relacion([sujeto(['Drugs', that]), verbo([prevent]), complemento(['Th2-cells', from, migrating, into, the, lung, 'tissue,', such, as, antibodies, to, the, chemokine, receptor, 'CCR4', and, inhibitors, of, the, adhesion, molecule, 'VLA-4,', are, promising, for, the, treatment, of, asthma])]). relacion([sujeto(['To']), verbo([inhibit]), complemento(['Th2-cell', 'activation,', novel, asthma, drugs, that, act, on, 'Th2-selective', transciption, factors, such, as, 'GATA3', are, being, developed])]). relacion([sujeto(['We', identified, and, characterized, a, new, 'C/T', substitution, at, position, -, 689, '(', -, 689, 'C>T)', in, the, 'P2', promoter, of, 'PPARgamma', in, a, putative, 'GATA']), verbo([binding]), complemento([site])]). relacion([sujeto(['By', electrophoretic, mobility, shift, 'assay,', both, 'GATA2', and, 'GATA3', proteins, could]), verbo([bind]), complemento([weakly, to, the, 'wild-type', 'P2', -, 689, 'GATA', binding, site, but, not, to, the, mutated, site])]). relacion([sujeto(['Neither', 'GATA2', nor, 'GATA3', was, able, to]), verbo([regulate]), complemento([significantly, the, 'P2', promoter, activity, in, a, 'reporter-luciferase', 'assay,', whatever, the, allele, at, position, -, 689, 'was,', suggesting, that, the, -, 689, putative, 'GATA', site, was, probably, not, a, functional, target, for, 'GATAs'])]). relacion([sujeto(['The', 'P3', -, 681, 'C>G,', 'P2', -, 689, 'C>T,', and, 'Pro12Ala', polymorphisms, and, related, haplotypes, were]), verbo([associated]), complemento([with, higher, body, weight, and, plasma, 'LDL-cholesterol', concentrations])]). relacion([sujeto(['Ligation', of, the, 146, -, bp, fragment, to, a, 'SV40', promoter, or, a, human, 'beta-globin', minimal, promoter, markedly]), verbo([enhanced]), complemento([promoter, activity, in, the, placenta, cells, but, not, in, the, liver, and, kidney, cells])]). relacion([sujeto(['DNase', 'I', footprint, assays, indicated, that]), verbo([nuclear]), complemento([extracts, from, 'BeWo', cells, but, not, 'HepG2', cells, protected, four, regions, '(', 'FP1-FP4)', of, the, 146, -, bp, fragment])]). relacion([sujeto(['Overexpression', of, 'SP1', '(', 'Sp1', transcription, 'factor)', and, 'GATA2', '(', 'GATA']), verbo([binding]), complemento([protein, 2, ')', and, 'GATA3', induced, syncytin, promoter, activity, but, had, little, or, no, effect, on, the, activities, of, syncytin, promoter, fragments, containing, mutations, in, the, 'SP1-', and, 'GATA-binding', sites])]). relacion([sujeto(['GATA2', and, -, 3, mRNA, levels]), verbo([increased]), complemento([markedly, during, spontaneous, in, vitro, differentiation, of, human, cytotrophoblast, cells, when, the, cytotrophoblast, cells, fused, to, form, a, syncytium])]). relacion([sujeto(['These', findings, strongly]), verbo([suggest]), complemento([that, the, 146, -, bp, region, of, the, 5, '\'', -, flanking, region, '(', 'nt-294/-148)', of, the, human, syncytin, gene, acts, as, a, 'placenta-specific', enhancer])]). relacion([sujeto(['As', genetic, variations, in, cytokine, genes, are, thought, to]), verbo([regulate]), complemento([cytokine, 'production,', we, studied, the, significance, of, this, polymorphism, for, 'IL2', transcription])]). relacion([sujeto(['Compared', to, unstimulated, 'cells,', stimulation, with, 'ConA', and, 'PMA/I']), verbo([increased]), complemento([the, 'IL2', mRNA, transcription, in, average, by, 300, -, and, 20, -, 'fold,', respectively])]). relacion([sujeto(['These', findings, were, confirmed, by, band, shift, studies, using, different, oligonucleotides, containing, variations, of, the, potential]), verbo([binding]), complemento(['motif,', which, showed, no, differences, in, the, gel, mobility, after, incubation, with, nuclear, extract, containing, 'GATA-3'])]). relacion([sujeto(['Thirty', percent, of, 'ERalpha-positive', breast, cancers, do, not]), verbo([respond]), complemento([to, hormonal, therapy])]). relacion([sujeto(['GATA-3', is, a, transcription, factor, that, is]), verbo([expressed]), complemento([in, association, with, 'ERalpha', and, there, is, evidence, that, 'GATA', factors, influence, response, to, estrogen])]). relacion([sujeto(['In', this, pilot, 'study,', we, investigated, whether, 'GATA-3', expression, is]), verbo([associated]), complemento([with, hormone, response, in, breast, cancer])]). relacion([sujeto(['Using', 20, '%']), verbo([nuclear]), complemento([staining, to, characterize, tumors, as, 'GATA-3', positive, or, 'GATA-3', 'negative,', 6, of, 14, '(', 43, '%', ')', cancers, in, the, 'hormone-unresponsive', group, and, none, of, the, controls, were, classified, as, 'GATA-3', negative, '(', odds, 'ratio,', 8.2, ;, 95, '%', confidence, 'interval,', 1.2, -, 'infinity;', p, =, 0.031, ')'])]). relacion([sujeto(['The', study]), verbo([suggests]), complemento([that, analyzing, 'ERalpha-positive', breast, tumors, for, 'GATA-3', using, immunohistochemistry, might, improve, prediction, of, hormone, responsiveness])]). relacion([sujeto(['The', association, between, 'GATA-3', expression, and, hormone, response]), verbo([suggests]), complemento([that, 'GATA-3', may, play, a, role, in, mechanisms, controlling, response, to, estrogen])]). relacion([sujeto(['The', 'authors\'', previous, study, showed, that, 'BCG']), verbo([promoted]), complemento([cord, blood, 'monocyte-derived', dendritic, cells, maturation, and, induced, high, level, of, interleukin, '(', 'IL)-10,', medium, level, of, interferon, '(', 'IFN)-gamma,', but, low, level, of, 'IL-4', production, by, cord, naive, 'T', cells])]). relacion([sujeto(['The', percentage, of, total, 'CD4(+)', 'T', cells]), verbo([decreased]), complemento(['[', '(', 23.5, +, /, -, 2.59, ')', '%', vs])]). relacion([sujeto(['Neonatal', 'BCG', vaccination, could]), verbo([induce]), complemento([strong, 'Th1', but, weak, 'Th2', response, as, reported, previously])]). relacion([sujeto(['Though', neonatal, 'BCG', vaccination, was, not, capable, of]), verbo([inducing]), complemento(['CD4(+)CD25(+)', regulatory, 'T', cell, response, with, 'Foxp3', 'expression,', it, caused, increase, of, 'IL-10(+)', 'CD3(+)', cells, which, might, represent, some, regulatory, 'T', cells, producing, 'IL-10'])]). relacion([sujeto(['NOD', 'CD8(+)', 'T', cells, had, an]), verbo([increased]), complemento([propensity, to, produce, 'IFN-gamma', upon, 'TCR', 'activation,', in, both, adult, and, 2, -, 'week-old', mice])]). relacion([sujeto(['Both', 'GATA-3', and, 'c-Maf,', two, positive, transactivators, for, 'IL-4', gene, 'expression,', were]), verbo([expressed]), complemento([in, type, 2, conditions, at, comparable, levels, in, 'NOD', 'CD8(+)', 'T', cells])]). relacion([sujeto(['In', 'contrast,', 'c-Maf', failed, to]), verbo([bind]), complemento([to, its, responsive, element, as, determined, by, chromatin, immunoprecipitation, '(', 'ChIP)', assay])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, 'NOD', 'CD8(+)', 'T', cells, possess, an, increased, propensity, to, produce, 'IFN-gamma', and, impaired, 'c-Maf-dependent', 'DNA', binding, activities, in, vivo, that, lead, to, reduced, 'IL-4', production, following, 'TCR', activation])]). relacion([sujeto(['These', defects, may, facilitate, the, development, of, the, autoimmune, response, by]), verbo([inducing]), complemento([an, overall, type, 1, -, biased, immune, response, in, 'NOD', mice])]). relacion([sujeto(['Recently,', a, member, of, the, 'GATA-binding', family, of, transcription, factors, was, shown, to, be]), verbo([involved]), complemento([in, human, 'hypoparathyroidism,', sensorineural, 'deafness,', and, renal, abnormality, '(', 'HDR)', syndrome])]). relacion([sujeto(['We']), verbo([report]), complemento([here, a, 'Japanese', family, in, which, two, of, the, members, are, affected, with, 'HDR', syndrome])]). relacion([sujeto(['Sequence', analysis, of, 'GATA3', showed, a, heterozygous, novel, mutation, in, this, 'family:', an, unusual, mutation, at, exon, 3, '(', 709, 'insC)', resulting, in, a, premature, stop, at, codon, 302, with, a]), verbo([loss]), complemento([of, both, of, the, zinc, finger, domains])]). relacion([sujeto(['Glucocorticoids', are, the, mainstay, of, asthma, therapy, and]), verbo([mediate]), complemento([the, repression, of, a, number, of, cytokine, 'genes,', such, as, 'Interleukin', '(', 'IL)-4,', -, 5, ',', -, 13, ',', and, granulocyte, macrophage, 'colony-stimulating', factor, '(', 'GM-CSF),', which, are, central, to, the, pathogenesis, of, asthmatic, airway, inflammation])]). relacion([sujeto(['The', glucocorticoid, receptor, '(', 'GR)']), verbo([mediates]), complemento([repression, by, a, number, of, diverse, mechanisms])]). relacion([sujeto(['We']), verbo([have]), complemento([previously, suggested, that, one, such, repressive, activity, is, by, direct, binding, of, 'GR', to, elements, within, the, 'GM-CSF', enhancer, that, are, recognized, by, the, nuclear, factor, of, activated, 'T', cells])]). relacion([sujeto(['We', reasoned, 'that,', because, many, cytokine, genes]), verbo([activated]), complemento([in, asthma, are, transcriptionally, regulated, by, the, recruitment, of, this, complex, to, 'DNA,', their, binding, sites, might, provide, a, target, for, 'GR', to, mediate, its, repressive, effects])]). relacion([sujeto(['Here,', we, show, that, transcriptional, repression, of, the, 'Interleukin-5', gene]), verbo([involves]), complemento([recruitment, of, 'GR', to, a, 'DNA', region, located, within, the, 'IL-5', proximal, 'promoter,', which, is, bound, by, 'NF-AT', and, 'AP-1', proteins])]). relacion([sujeto(['GR', recruitment, had, a, profound, effect, upon, the, activation, capacity, of, 'GATA3,', which]), verbo([has]), complemento([a, binding, site, close, to, the, 'NF-AT'])]). relacion([sujeto(['Repression', by, 'GR']), verbo([involves]), complemento(['co-repressor', 'recruitment,', because, treatment, of, transfected, cells, with, the, deacetylase, inhibitor, trichostatin, 'A', caused, a, partial, relief, of, repression])]). relacion([sujeto(['These', data]), verbo([suggest]), complemento([that, the, local, recruitment, of, 'GR', causes, repression, by, inhibiting, transcriptional, activation, by, 'GATA3,', a, key, 'tissue-specific', determinant, of, expression, of, 'Th2', cytokines])]). relacion([sujeto([15, -, 'Deoxy-delta(12,', 14, ')', -, prostaglandin, 'J2', '(', 15, 'd-PG', 'J2)', is, a, regulator, of, a]), verbo([nuclear]), complemento([transcriptional, 'factor,', peroxisome, 'proliferator-activated', receptor, '(', 'PPAR)-gamma'])]). relacion([sujeto(['A', previous, study]), verbo([has]), complemento([demonstrated, that, 15, 'd-PG', 'J2', enhanced, acute, lung, injury, induced, by, lipopolysaccharide, '(', 'LPS)', in, mice])]). relacion([sujeto([15, 'd-PG', 'J2']), verbo([induced]), complemento(['mucin-producing', cells, in, the, bronchial, 'epithelium,', especially, in, the, presence, of, 'LPS'])]). relacion([sujeto(['The']), verbo([nuclear]), complemento([localization, of, 'GATA-3', and, phosphorylated, 'STAT', 6, was, evaluated, 2, h, after, the, intratracheal, administration])]). relacion([sujeto([15, 'd-PG', 'J2']), verbo([enhanced]), complemento([the, nuclear, localization, of, 'GATA-3', in, the, presence, of, 'LPS,', whereas, the, nuclear, localization, of, phosphorylated, 'STAT', 6, was, not, altered, in, the, groups])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, the, enhancing, effects, of, 15, 'd-PG', 'J2', on, the, production, of, 'mucin-producing', cells, might, be, 'related,', at, least, in, 'part,', to, the, activation, of, 'GATA-3'])]). relacion([sujeto(['paratuberculosis)']), verbo([leads]), complemento([to, a, chronic, and, often, fatal, granulomatous, enteritis, known, as, 'Johne\'s', disease])]). relacion([sujeto(['Recent', 'gene-expression', profiling, studies]), verbo([suggested]), complemento([the, hypothesis, that, inherent, 'gene-expression', profiles, in, peripheral, blood, mononuclear, cells, '(', 'PBMCs)', from, 'M'])]). relacion([sujeto(['If', 'true,', this, would]), verbo([suggest]), complemento([that, it, is, possible, to, identify, an, 'M'])]). relacion([sujeto(['paratuberculosis-infected', cows]), verbo([have]), complemento([adopted, a, predominant, 'Th', 2, -, like, phenotype, '(', enhanced, expression, of, 'IL-5,', 'GATA', 3, ',', and, possibly, 'IL-4', 'mRNA),', that, cells, within, infected, cow, 'PBMCs', may, exhibit, tissue, remodeling, deficiencies, through, higher, expression, of, tissue, inhibitor, of, matrix, metalloproteinase, '(', 'TIMP)', 1, and, 'TIMP2', 'RNA', and, lower, expression, of, matrix, metalloproteinase, '(', 'MMP)', 14, 'RNA', than, similar, cells, from, healthy, 'controls,', and, that, cells, within, the, 'PBMC', population, of, 'M'])]). relacion([sujeto(['Transforming', growth, factor, '(', 'TGF)-beta,', a, pleiotropic, cytokine, that]), verbo([has]), complemento([multiple, effects, on, immune, 'responses,', has, been, shown, to, inhibit, interleukin, '(', 'IL)-4/GATA-3', expression, as, well, as, 'T', helper, 2, '(', 'Th2)', differentiation])]). relacion([sujeto(['Consistent', with, these, 'reports,', we]), verbo([found]), complemento([that, priming, 'T', cells, from, 'DO11'])]). relacion([sujeto([10, transgenic, mice, with, antigen, in, the, presence, of, 'TGF-beta']), verbo([inhibited]), complemento(['GATA-3', expression, and, the, development, of, 'IL-4-producing', 'T', cells])]). relacion([sujeto(['Unexpectedly,', the, inhibition, of, 'Th2', development, was, accompanied, by, a, substantial]), verbo([increase]), complemento([in, the, number, of, 'interferon-gamma', '(', 'IFN-gamma)-producing', cells])]). relacion([sujeto(['T', cells, primed, with, 'TGF-beta', secreted, 'IFN-gamma', in, response, to, both, 'T-cell', receptor, ligation, and, 'IL-12/IL-18', 'stimulation,', and]), verbo([expressed]), complemento([high, levels, of, 'T-bet', and, low, levels, of, 'GATA-3'])]). relacion([sujeto(['The', 'TGF-beta-mediated', enhancement, of, 'T', helper, 1, '(', 'Th1)', priming, was, independent, of, 'IL-12', and, signal, transducer, and, activator, of, transcription, '(', 'STAT)-4,', but]), verbo([required]), complemento([endogenous, 'IFN-gamma'])]). relacion([sujeto(['TGF-beta-mediated', enhancement, of, the, 'IFN-gamma-dependent,', 'IL-12-independent', pathway, of, 'Th1', priming, was]), verbo([mediated]), complemento([primarily, by, the, inhibition, of, 'IL-4', produced, by, 'memory/activated', 'T', cells, in, the, unfractionated, 'CD4+', responder, population])]). relacion([sujeto(['Nevertheless,', 'TGF-beta', did, not]), verbo([inhibit]), complemento([this, pathway, of, 'Th1', differentiation, when, purified, naive, 'CD4+', 'T', cells, were, used, as, responders])]). relacion([sujeto(['These', data]), verbo([have]), complemento([important, implications, for, strategies, being, considered, for, the, use, of, 'TGF-beta-producing', 'T', cells, for, the, treatment, of, autoimmune, disorders])]). relacion([sujeto(['The', 'TEC-family', protein, tyrosine, kinases, 'ITK,', 'RLK', and, 'TEC']), verbo([have]), complemento([been, identified, as, key, components, of, 'T-cell-receptor', signalling, that, contribute, to, the, regulation, of, phospholipase, 'C-gamma,', the, mobilization, of, 'Ca(2+)', and, the, activation, of, 'mitogen-activated', protein, kinases])]). relacion([sujeto(['Recent', data, also, show, that, 'TEC', kinases, contribute, to, 'T-cell-receptor-driven', actin, reorganization, and, cell, 'polarization,', which, are]), verbo([required]), complemento([for, productive, 'T-cell', activation])]). relacion([sujeto(['Functional', studies]), verbo([have]), complemento([implicated, 'TEC', kinases, as, important, mediators, of, pathways, that, control, the, differentiation, of, 'CD4(+)', 'T', helper, cells])]). relacion([sujeto(['Here,', we, review, studies, of, signalling, pathways, that]), verbo([involve]), complemento(['TEC', kinases, and, how, these, pathways, might, contribute, to, the, regulation, of, 'T-helper-cell', differentiation, and, function])]). relacion([sujeto(['In', 'conclusion,', altered, 'Th1', reaction, as, reflected, by, lower, 'T-bet', mRNA, expression]), verbo([associated]), complemento([with, higher, 'IL-10', levels, might, be, involved, in, the, pathogenesis, of, dengue, hemorrhagic, fever])]). relacion([sujeto(['Ginsenoside-Rh', '(', 1, ')', and, 20, '(', 'R)-Rh', '(', 1, ')']), verbo([induce]), complemento([a, 'Con', 'A-induced', type, 1, cytokine, pattern, by, increasing, the, production, of, 'interleukin-12', '(', 'IL-12),', the, expression, of, 'IFN-gamma,', 'T-bet', and, enhancing, 'NF-kappaB', 'DNA', binding, activity])]). relacion([sujeto(['In', contrast, 'ginsenosides-Rg', '(', 1, ')', and, -, 'F', '(', 1, ')']), verbo([cause]), complemento([a, 'Con', 'A-induced', type, 2, cytokines, response, by, increasing, the, expression, of, 'IL-4,', 'GATA-3', and, enhancing, 'NF-kappaB', 'DNA', binding, activity])]). relacion([sujeto(['Thus,', these, 'protopanaxatriol-type', ginsenosides]), verbo([have]), complemento([different, immunomodulatory, 'effects,', which, might, explain, the, complex, immunomodulatory, effect, of, 'Panax', ginseng])]). relacion([sujeto(['We', pursued, to, identify, the, potential, 'Gata3']), verbo([target]), complemento([genes, by, profiling, the, gene, expression, pattern, in, 'E9'])]). relacion([sujeto(['The', majority, of, the, differentially]), verbo([expressed]), complemento([genes, belong, to, two, functional, 'groups--genes', involved, in, transcription, regulation, and, cellular, signaling])]). relacion([sujeto(['The', validity, of, this]), verbo([finding]), complemento([was, checked, by, using, the, whole, mount, in, situ, hybridization, technology])]). relacion([sujeto(['Interleukin-7', '(', 'IL-7)']), verbo([promotes]), complemento([survival, and, expansion, of, lymphoid, precursors])]). relacion([sujeto(['We', show, here, 'that,', in, 'addition,', 'IL-7']), verbo([has]), complemento([a, fundamental, 'role,', as, early, as, the, stage, of, the, multipotent, '(', 'B/T/NK)', common, lymphoid, progenitor, '(', 'CLP),', in, maintaining, the, 'B', cell, differentiation, program, open])]). relacion([sujeto(['CLPs', generated, in, the, absence, of, 'IL-7']), verbo([have]), complemento([normal, 'T/NK', differentiation, 'potential,', but, severely, impaired, 'B', potential])]). relacion([sujeto(['Accordingly,', 'CLPs', from, 'IL-7-deficient', mice]), verbo([express]), complemento([lower, amounts, of, early, 'B', cell, factor, '(', 'EBF)', and, 'Pax5', than, 'wild-type', 'CLPs,', but, similar, amounts, of, 'GATA-3'])]). relacion([sujeto(['Importantly,']), verbo([induced]), complemento([overexpression, of, 'EBF', is, sufficient, to, restore, the, 'B', potential, in, these, cells])]). relacion([sujeto(['These', results, indicate, that, 'IL-7', directs, commitment, of, 'CLPs', by]), verbo([modulating]), complemento(['EBF', expression])]). relacion([sujeto(['In', this, 'study,', we]), verbo([have]), complemento([examined, the, effect, of, inhibition, of, caspases, on, the, process, of, 'Th1/Th2', differentiation])]). relacion([sujeto(['Naive', 'CD4+', 'T', cells]), verbo([activated]), complemento([under, neutral, differentiation, conditions, in, the, presence, of, the, pan, caspase, inhibitor, 'benzyloxycarbonyl-Val-Ala-Asp', '(', 'Z-VAD)', fluoromethylketone, showed, increased, 'Th2', cell, differentiation, concomitant, with, an, 'up-regulation', of, 'GATA-3'])]). relacion([sujeto(['Z-VAD']), verbo([induced]), complemento([optimal, 'Th2', differentiation, when, 'T', cells, were, stimulated, under, strong, primary, activation, conditions])]). relacion([sujeto(['Treatment', of, naive, 'CD4+', 'T', cells, with, 'Z-VAD', under, strong, activation, conditions]), verbo([led]), complemento([to, a, 6, -, fold, increase, in, 'IL-4', mRNA, compared, with, 'control-treated', 'T', cells])]). relacion([sujeto(['The', 'Z-VAD-induced']), verbo([increase]), complemento([in, 'IL-4', transcription, occurred, within, 24, h, of, activation, and, was, independent, of, 'Stat6'])]). relacion([sujeto(['Z-VAD', did, not, augment, 'IL-4', expression, from, a, committed, 'Th2', 'cell,']), verbo([suggesting]), complemento([that, caspases, regulate, 'IL-4', expression, specifically, during, primary, 'T', cell, activation])]). relacion([sujeto(['Activation', of, 'T', cells, in, the, presence, of, 'Z-VAD']), verbo([led]), complemento([to, a, specific, increase, in, the, expression, of, the, transcription, factor, 'c-fos'])]). relacion([sujeto(['Lastly,', 'retrovirus-mediated', expression, of, the, antiapoptotic, protein, 'Bcl-2', resulted, in, an, enhancement, of, 'Th2', cytokine, 'expression,']), verbo([suggesting]), complemento([that, inhibition, of, caspase, activation, by, 'Bcl-2', can, also, modulate, 'IL-4', expression])]). relacion([sujeto(['These', findings]), verbo([reveal]), complemento([a, novel, regulatory, mechanism, of, cytokine, expression, by, 'caspases,', and, may, explain, how, signaling, pathways, that, inhibit, apoptosis, tend, to, promote, 'Th2', differentiation])]). relacion([sujeto(['Extracellular', heat, shock, protein, 60, '(', 'HSP60)']), verbo([has]), complemento([been, considered, a, proinflammatory, danger, signal])]). relacion([sujeto(['We', now]), verbo([report]), complemento([that, 'HSP60', in, vitro, differentially, modulates, the, expression, of, 'Th1/Th2', transcription, factors, in, human, 'T', 'cells:', 'HSP60', 'down-regulates', 'T-bet,', 'NF-kappaB,', and, 'NFATp', and, 'up-regulates', 'GATA-3,', leading, to, decreased, secretion, of, 'TNF-alpha', and, 'IFN-gamma', and, enhanced, secretion, of, 'IL-10'])]). relacion([sujeto(['In', 'BALB/c', 'mice,', 'HSP60', in, vivo]), verbo([inhibited]), complemento([the, 'clinical,', 'histological,', and, serological, manifestations, of, 'Con', 'A-induced', hepatitis, associated, with, 'up-regulated', 'T', cell, expression, of, suppressor, of, cytokine, signaling, 3, and, 'GATA-3', and, 'down-regulated', 'T-bet', expression])]). relacion([sujeto(['These', results]), verbo([provide]), complemento([a, molecular, explanation, for, the, effects, of, 'HSP60', treatment, on, 'T', cell, inflammation, via, innate, regulation, of, the, inflammatory, response])]). relacion([sujeto(['ST2', is, a, member, of, the, 'interleukin-1', receptor, family, and, is]), verbo([expressed]), complemento([in, 'type-2', 'T', helper, '(', 'Th2)', cells])]). relacion([sujeto(['Here,', we]), verbo([have]), complemento([studied, the, molecular, mechanism, responsible, for, the, transcriptional, regulation, of, the, 'ST2', gene, in, 'Th2', cells, using, a, mouse, thymoma, cell, 'line,', 'EL-4'])]). relacion([sujeto(['The', 'ST2', gene]), verbo([has]), complemento([distal, and, proximal, promoters])]). relacion([sujeto(['ST2', mRNA, was, produced, from, the, distal, promoter, in, 'EL-4', cells]), verbo([stimulated]), complemento([with, both, phorbol, 12, -, myristate, 13, -, acetate, '(', 'PMA)', and, dibutyryl, cAMP, '(', 'Bt2cAMP)'])]). relacion([sujeto(['An', electrophoretic, mobility, shift, assay, showed, that, transcription, factor, 'GATA-3']), verbo([bound]), complemento([one, of, the, 'GATA', consensus, sites, '(', from, -, 84, to, -, 79, ')', with, nuclear, extracts, from, 'PMA', plus, 'Bt2cAMP-stimulated', 'EL-4', cells])]). relacion([sujeto(['The', overexpression, of, 'GATA-3']), verbo([enhanced]), complemento([the, activity, of, the, distal, promoter])]). relacion([sujeto(['These', data]), verbo([suggest]), complemento([that, 'GATA-3', is, an, important, transcription, factor, for, the, expression, of, the, 'ST2', gene, in, 'Th2', cells])]). relacion([sujeto(['The', 'hypoparathyroidism,', 'deafness,', and, renal, dysplasia, '(', 'HDR)', syndrome, is, an, autosomal, dominant, disorder]), verbo([caused]), complemento([by, mutations, of, a, member, of, the, 'GATA-binding', family, of, transcription, 'factors,', 'GATA3'])]). relacion([sujeto(['This', dual, zinc, finger, transcription, factor]), verbo([binds]), complemento(['DNA', with, its, 'C-terminal', zinc, finger, '(', 'ZnF2)', and, stabilizes, this, binding, with, its, 'N-terminal', zinc, finger, '(', 'ZnF1)'])]). relacion([sujeto(['ZnF1', also]), verbo([interacts]), complemento([with, other, zinc, finger, 'proteins,', notably, 'Friend', of, 'GATA', '(', 'FOG)'])]). relacion([sujeto(['The', 'HDR', syndrome]), verbo([has]), complemento([been, described, in, patients, with, mutations, affecting, both, 'ZnF1', and, 'ZnF2', 'domains;', the, former, result, in, inefficient, interaction, with, 'FOG,', and, the, latter, result, in, disruption, of, 'DNA', binding])]). relacion([sujeto(['We']), verbo([report]), complemento([a, patient, with, renal, 'failure,', 'hypoparathyroidism,', and, bilateral, hearing, loss])]). relacion([sujeto(['Functional', analysis, using, dissociation, electrophoretic, mobility, shift, and, yeast, 'two-hybrid', assays, showed, reduced]), verbo([binding]), complemento([affinity, to, the, 'GATA', motifs, but, normal, interaction, with, 'FOG', in, vitro])]). relacion([sujeto(['CD94/NKG2A', is, an, inhibitory, receptor]), verbo([expressed]), complemento([by, most, human, 'NK', cells, and, a, subset, of, 'T', cells, that, recognizes, 'HLA-E', on, potential, target, cells])]). relacion([sujeto(['Using', deletion, 'mutants,', we, identified, a, region, immediately, upstream, from, the, most, upstream, transcriptional, initiation, site, that]), verbo([led]), complemento([to, increased, transcriptional, activity, from, a, luciferase, reporter, construct, in, 'YT-Indy', '(', 'NKG2A', 'positive)', cells, relative, to, 'Jurkat', and, 'K562', '(', both, 'NKG2A', 'negative)', cells])]). relacion([sujeto(['Within', this, 80, -, bp, 'segment,', we, identified, two, 'GATA']), verbo([binding]), complemento([sites])]). relacion([sujeto(['Mutation', of, 'GATA']), verbo([binding]), complemento([site, 'II', '(', -, 2302, 'bp)', but, not, 'GATA', binding, site, 'I', '(', -, 2332, 'bp)', led, to, decreased, transcriptional, activity])]). relacion([sujeto(['Pull-down', assays, revealed, that, 'GATA-3', could]), verbo([bind]), complemento([oligonucleotide, probes, containing, the, wild, type, but, not, a, mutated, 'GATA', site, 'II'])]). relacion([sujeto(['Using', chromatin, immunoprecipitation, 'assays,', we, showed, that, 'GATA-3', specifically]), verbo([binds]), complemento([to, the, 'NKG2A', promoter, in, situ, in, 'NKL', and, primary, 'NK', 'cells,', but, not, in, 'Jurkat', 'T', cells])]). relacion([sujeto(['Moreover,', coexpression, of, human, 'GATA-3', with, an, 'NKG2A', promoter, construct, in, 'K562', cells]), verbo([led]), complemento([to, enhanced, promoter, 'activity,', and, transfection, of, 'NKL', cells, with, small, interfering, 'RNA', specific, for, 'GATA-3', reduced, 'NKG2A', cell, surface, expression])]). relacion([sujeto(['Taken', 'together,', our, data, indicate, that, 'GATA-3', is, an, important, transcription, factor, for]), verbo([regulating]), complemento(['NKG2A', gene, expression])]). relacion([sujeto(['Although', accumulated, data]), verbo([suggest]), complemento([that, 'ICOS', costimulatory, signals, play, an, important, role, in, 'Th2-mediated', immune, 'responses,', the, molecular, basis, for, this, selective, differentiation, mechanism, is, largely, unknown])]). relacion([sujeto(['Unlike', previous, 'reports,', we]), verbo([found]), complemento([that, primary, 'IL-4', production, by, these, 'T', cells, was, intact, and, that, 'IL-4R', sensitivity, of, these, 'T', cells, was, reduced, as, evidenced, by, a, profound, defect, in, 'IL-4-induced', 'Stat6', phosphorylation, and, the, early, induction, of, 'GATA-3'])]). relacion([sujeto(['The', fact, that, 'ICOS', ligation, of, 'wild-type', 'T', cells, significantly]), verbo([enhanced]), complemento(['IL-4-induced', 'Stat6', phosphorylation, and, primary, 'GATA-3', 'induction,', but, not, 'IL-4', 'transcription,', of, naive, 'CD4+', 'T', cells, was, consistent, with, the, results, obtained, from, 'ICOS-/-', 'T', cell, experiments])]). relacion([sujeto(['These', observations]), verbo([led]), complemento([us, to, propose, that, the, predominant, effect, of, 'ICOS-mediated', costimulation, on, 'Th2', differentiation, is, achieved, by, the, enhancement, of, 'IL-4R-mediated', signaling])]). relacion([sujeto(['Vertebrates', possess, at, least, three, 'Shn', orthologues, '(', 'Shn-1,', 'Shn-2,', and, 'Shn-3),', which, appear, to]), verbo([act]), complemento([within, the, bone, morphogenetic, 'protein,', transforming, growth, factor, 'beta,', and, activin, signaling, pathways])]). relacion([sujeto(['Shn-2-deficient', developing, 'Th2', cells, showed, constitutive, activation, of]), verbo([nuclear]), complemento([factor, kappaB, '(', 'NF-kappaB)', and, enhanced, 'GATA3', induction])]). relacion([sujeto(['Shn-2', was, able, to, compete, with, p50, 'NF-kappaB', for]), verbo([binding]), complemento([to, a, consensus, 'NF-kappaB', motif, and, inhibit, 'NF-kappaB-driven', promoter, activity])]). relacion([sujeto(['Thus,', 'Shn-2', plays, a, crucial, role, in, the, control, of, 'Th2', cell, differentiation, by]), verbo([regulating]), complemento(['NF-kappaB', function])]). relacion([sujeto(['Several', excellent, gene, expression, profiles]), verbo([have]), complemento([been, obtained, of, the, total, hematopoietic, stem, cell, population])]). relacion([sujeto(['We']), verbo([have]), complemento([used, 'five-color', 'FACS', sorting, to, isolate, separate, populations, of, 'LTR', and, 'STR', stem, cell, subsets])]). relacion([sujeto(['The', 'LTR', 'HSC']), verbo([has]), complemento([the, phenotype, defined, as, 'Lin-', 'Sca+', 'Kit+', 38, +, 34, -, ;, two, subsets, of, 'STR', 'HSC', were, obtained, with, phenotypes, of, 'Lin-', 'Sca+', 'Kit+', 38, +, 34, +, and, 'Lin-', 'Sca+', 'Kit+', 38, -, 34, +])]). relacion([sujeto(['The', microarray, profiling, study]), verbo([reported]), complemento([here, was, able, to, identify, genes, specific, for, 'LTR', functions])]). relacion([sujeto(['In', the, interrogated, genes, '(', approximately, 12, ',', 0, probe, sets, corresponding, to, 8, ',', 0, 'genes),', 210, genes, are, differentially, 'expressed,', and, 72, genes, are]), verbo([associated]), complemento([with, 'LTR', 'activity,', including, membrane, 'proteins,', signal, transduction, 'molecules,', and, transcription, factors])]). relacion([sujeto(['Hierarchical', clustering, of, the, 210, differentially]), verbo([expressed]), complemento([genes, suggested, that, they, are, not, bone, 'marrow-specific', but, rather, appear, to, be, stem, 'cell-specific'])]). relacion([sujeto(['Transcription', 'factor-binding', site, analysis]), verbo([suggested]), complemento([that, 'GATA3', might, play, an, important, role, in, the, biology, of, 'LTR', 'HSC'])]). relacion([sujeto(['Cell', lineage, specification, depends, on, both, gene, activation, and, gene, 'silencing,', and, in, the, differentiation, of, 'T', helper, progenitors, to, 'Th1', or, 'Th2', effector, 'cells,', this]), verbo([requires]), complemento([the, action, of, two, opposing, transcription, 'factors,', 'T-bet', and, 'GATA-3'])]). relacion([sujeto(['We']), verbo([report]), complemento([that, 'T-bet', represses, 'Th2', lineage, commitment, through, tyrosine, 'kinase-mediated', interaction, between, the, two, transcription, factors, that, interferes, with, the, binding, of, 'GATA-3', to, its, target, 'DNA'])]). relacion([sujeto(['These', results]), verbo([provide]), complemento([a, novel, function, for, tyrosine, phosphorylation, of, a, transcription, factor, in, specifying, alternate, fates, of, a, common, progenitor, cell])]). relacion([sujeto(['The', six, vertebrate, 'GATA', factors, are, highly]), verbo([conserved]), complemento([in, zebrafish, at, the, level, of, 'sequence,', expression, 'pattern,', and, function])]). relacion([sujeto(['The', identification, of, 'mutants,', establishment, of, transgenic, 'GFP', reporter, 'fish,', and, the, ease, of, performing, 'loss-', and, 'gain-of-function', experiments]), verbo([have]), complemento([all, contributed, new, insight, into, our, understanding, of, the, regulation, and, function, of, 'GATA', factors])]). relacion([sujeto(['We', review, recent, advances, toward, this, goal, using, the, zebrafish, system, with, a, focus, on, hematopoiesis, and, 'cardiogenesis,', and]), verbo([suggest]), complemento([how, comparative, genetics, using, the, zebrafish, genes, might, reveal, core, conserved, 'properties,', as, well, as, changes, in, gene, function, that, reflect, different, morphogenetic, programs, utilized, by, various, vertebrate, embryos])]). relacion([sujeto(['GATA', factors]), verbo([regulate]), complemento([critical, events, in, hematopoietic, lineages, '(', 'GATA-1/2/3),', the, heart, and, gut, '(', 'GATA-4/5/6)', and, various, other, tissues])]). relacion([sujeto(['Transgenic', approaches]), verbo([have]), complemento([revealed, that, 'GATA', genes, are, regulated, in, a, modular, fashion, by, sets, of, enhancers, that, govern, distinct, temporal, 'and/or', spatial, facets, of, the, overall, expression, patterns])]). relacion([sujeto(['Efforts', are, underway, to, resolve, how, these, 'GATA', gene, enhancers, are, themselves]), verbo([regulated]), complemento([in, order, to, elucidate, the, genetic, and, molecular, hierarchies, that, govern, 'GATA', expression, in, particular, developmental, contexts])]). relacion([sujeto(['The', transcription, factors, 'STAT6,', 'GATA3,', and, 'STAT4']), verbo([mediate]), complemento([the, 'cytokine-induced', development, of, naive, 'CD4', +, 'T', cells, into, either, 'T', 'H', 1, or, 'T', 'H', 2, type])]). relacion([sujeto(['We', studied, genetic, variation, of, the, 'STAT6,', 'GATA3,', and, 'STAT4', genes, and, examined, whether, single, nucleotide, polymorphisms, '(', 'SNPs)', in, these, loci, were]), verbo([associated]), complemento([with, asthma, or, serum, high, 'IgE', levels, in, the, 'Finnish', asthmatic, families])]). relacion([sujeto(['All', identified, 'SNPs', were, genotyped, in, 120]), verbo([nuclear]), complemento(['families,', and, the, haplotypes, were, analyzed, by, 'Haplotype', 'Pattern', 'Mining', based, statistical, analysis])]). relacion([sujeto(['Interestingly,', a, haplotype, analysis, of, 'GATA3', showed, 3, related, haplotypes, that]), verbo([associated]), complemento([with, different, asthma, and, atopy, related, phenotypes, among, both, the, family, and, 'case-control', data, sets])]). relacion([sujeto(['Elucidation', of, the, importance, of, the, identified, panel, of, 'SNPs', in, other, 'T', 'H', 1, /, 'T', 'H', 2]), verbo([mediated]), complemento([diseases, will, be, of, great, interest])]). relacion([sujeto(['We']), verbo([have]), complemento([previously, demonstrated, that, 'GATA-2', and, 'GATA-3', are, expressed, in, adipocyte, precursors, and, control, the, 'preadipocyte-to-adipocyte', transition])]). relacion([sujeto(['Constitutive', expression, of, both, 'GATA-2', and, 'GATA-3']), verbo([suppressed]), complemento([adipocyte, 'differentiation,', partially, through, direct, binding, to, the, peroxisome, 'proliferator-activated', receptor, gamma, '(', 'PPARgamma)', promoter, and, suppression, of, its, basal, activity])]). relacion([sujeto(['In', the, present, 'study,', we, demonstrate, that, both, 'GATA-2', and, 'GATA-3', form, protein, complexes, with, 'CCAAT/enhancer']), verbo([binding]), complemento([protein, alpha, '(', 'C/EBPalpha)', and, 'C/EBPbeta,', members, of, a, family, of, transcription, factors, that, are, integral, to, adipogenesis])]). relacion([sujeto(['The', interaction, between, 'GATA', and, 'C/EBP', factors, is, critical, for, the, ability, of, 'GATA', to]), verbo([suppress]), complemento([adipocyte, differentiation])]). relacion([sujeto(['Thus,', these, results, show, that, in, addition, to, its, previously]), verbo([recognized]), complemento([function, in, suppressing, 'PPARgamma', transcriptional, 'activity,', interaction, of, 'GATA', factors, with, 'C/EBP', is, necessary, for, their, ability, to, negatively, regulate, adipogenesis])]). relacion([sujeto(['Since', 'Hodgkin', and, 'Reed-Sternberg', '(', 'HRS)', cells, of, 'Hodgkin', lymphoma, '(', 'HL)', generally]), verbo([have]), complemento([immunoglobulin, gene, 'rearrangements,', they, are, considered, to, be, of, 'B-cell', origin])]). relacion([sujeto(['Expression', of, four, 'T-cell', 'TFs', and, the]), verbo([target]), complemento([cytokine, spectrum, of, these, 'TFs', were, analyzed, in, six, 'HL', and, three, large, 'B-cell', lymphoma, '(', 'LBCL)', cell, lines, using, quantitative, 'PCR'])]). relacion([sujeto(['Out', of, 'HL', cell, 'lines,', 'T-bet', was]), verbo([expressed]), complemento([in, 'five,', 'GATA-3', in, 'four,', and, 'c-Maf', in, two, cell, lines])]). relacion([sujeto(['Embryonic', vascular, 'formation,', 'vasculogenesis,', is, a, sequential, process, that]), verbo([involves]), complemento([complex, regulatory, cascades])]). relacion([sujeto(['Two', main, clusters, were, 'identified-one', of, 'down-regulated', genes, such, as, 'POU5,', 'NANOG,', 'TDGF1/Cripto', '(', 'TDGF,', 'teratocarcinoma-derived', growth, 'factor-1),', 'LIN28,', 'CD24,', 'TERF1', '(', telomeric, repeat]), verbo([binding]), complemento(['factor-1),', 'LEFTB', '(', 'left-right', 'determination,', factor, 'B),', and, a, second, of, 'up-regulated', genes, such, as, 'TWIST,', 'WNT5A,', 'WT1,', 'AFP,', 'ALB,', 'NCAM1'])]). relacion([sujeto(['Focusing', on, the, vascular, system, 'development,', genes, known, to, be]), verbo([involved]), complemento([in, vasculogenesis, and, angiogenesis, were, explored])]). relacion([sujeto(['The', reproducibility, of, the, array, data, was, verified, independently, and, illustrated, that, many, genes, known, to, be]), verbo([involved]), complemento([in, vascular, development, are, activated, during, the, differentiation, of, hESCs, in, culture])]). relacion([sujeto(['Success', in, treating, severe, sepsis, will]), verbo([require]), complemento([relevant, tools, to, monitor, the, patient, immunoinflammatory, status])]). relacion([sujeto(['At', the, onset, of, 'shock,', compared, to, healthy, 'volunteers,', mRNA, levels, in, septic, shock, patients, were]), verbo([increased]), complemento([for, 'IL-10,', 'IL-1beta,', and, high, mobility, group, 'B1', '(', 'HMGB1)', and, decreased, for, transforming, growth, factor, beta, 1, ',', the, 'Th1,', and, 'Th2', transcription, 'factors,', 'T-bet', and, 'GATA-3,', respectively])]). relacion([sujeto(['Single', parameter, analysis, highlighted, an]), verbo([increased]), complemento([expression, of, 'IL-10', and, 'HMGB1', mRNA, in, nonsurvivors, and, a, significant, rise, over, time, of, 'GATA3', in, survivors])]). relacion([sujeto(['With', a, growing, number, of, partly, or, fully, sequenced, vertebrate, 'genomes,', effective, tools, for, performing, multiple, comparisons, are]), verbo([required]), complemento([to, accurately, and, efficiently, assist, biological, discoveries])]). relacion([sujeto(['org/),', a, novel, method, and, a, network, server, for, comparing, multiple, draft, and, 'finished-quality', sequences, to, identify, functional, elements]), verbo([conserved]), complemento([over, evolutionary, time])]). relacion([sujeto(['Mulan', brings, together, several, novel, 'algorithms:', the, 'TBA', 'multi-aligner', program, for, rapid, identification, of, local, sequence, 'conservation,', and, the, multiTF, program, for, detecting, evolutionarily]), verbo([conserved]), complemento([transcription, factor, binding, sites, in, multiple, alignments])]). relacion([sujeto(['In', 'addition,', 'Mulan', supports, 'two-way', communication, with, the, 'GALA', 'database;', alignments, of, multiple, species, dynamically, generated, in, 'GALA', can, be, viewed, in, 'Mulan,', and]), verbo([conserved]), complemento([transcription, factor, binding, sites, identified, with, 'Mulan/multiTF', can, be, integrated, and, overlaid, with, extensive, genome, annotation, data, using, 'GALA'])]). relacion([sujeto(['Local', multiple, alignments, computed, by, 'Mulan']), verbo([ensure]), complemento([reliable, representation, of, 'short-', and, 'large-scale', genomic, rearrangements, in, distant, organisms])]). relacion([sujeto(['Mulan', allows, for, interactive, modification, of, critical, conservation, parameters, to, differentially, predict]), verbo([conserved]), complemento([regions, in, comparisons, of, both, closely, and, distantly, related, species])]). relacion([sujeto(['We', illustrate, the, uses, and, applications, of, the, 'Mulan', tool, through, multispecies, comparisons, of, the, 'GATA3', gene, locus, and, the, identification, of, elements, that, are]), verbo([conserved]), complemento([in, a, different, way, in, avians, than, in, other, 'genomes,', allowing, speculation, on, the, evolution, of, birds])]). relacion([sujeto(['Upon', 'TCR-triggering', with, suboptimal, doses, of, 'anti-CD3,', costimulation, of, naïve, 'CD4+', 'T', cells, with, 'anti-CD28', mAb, or, 'B7-Ig', fusion, proteins]), verbo([led]), complemento([to, comparable, levels, of, 'IFN-gamma', production])]). relacion([sujeto(['IL-4-selective', upregulation, was, also, observed, when, 'T', cells, from, 'anti-OVA', 'TCR', transgenic, mice, were]), verbo([stimulated]), complemento([with, 'OVA', in, the, presence, of, 'B7-Ig'])]). relacion([sujeto(['Correlating', with, 'IL-4', 'expression,', 'GATA-3', expression, was]), verbo([induced]), complemento([much, more, potently, by, costimulation, with, 'B7-Ig', than, with, 'anti-CD28', 'mAb,', while, 'T-bet', induction, by, these, two, costimulatory, reagents, was, comparable])]). relacion([sujeto(['This', 'B7', effect, was, also, applied, for, naïve, and, 'antigen-primed', 'CD8+', 'T', 'cells:', 'IL-4-expressing', 'CD8+', 'T', cells, were, generated, when, naïve, and, 'alloantigen-primed', 'T', cells, were]), verbo([stimulated]), complemento([with, 'anti-CD3', and, recall, 'antigens,', 'respectively,', in, the, presence, of, 'B7-Ig', costimulation])]). relacion([sujeto(['Importantly,', such, 'CD8+', 'T', cell, differentiation]), verbo([required]), complemento([the, coexistence, of, 'CD4+', 'T', cells, during, the, initial, 'TCR', stimulation])]). relacion([sujeto(['These', observations, indicate, that, both, type, 2, 'CD4', and, 'CD8', 'T', cell, polarizations, are, efficiently]), verbo([induced]), complemento([via, costimulation, of, 'CD28', with, its, natural, 'ligands,', although, the, differentiation, of, 'CD8+', 'T', cells, is, dependent, on, 'CD4+', cells])]). relacion([sujeto(['To', test, the, efficacy, of, combined, 'high-throughput', analyses, '(', 'HTA)', in]), verbo([target]), complemento([gene, 'identification,', screening, criteria, were, set, using, &, 'gt;fivefold', difference, by, microarray, and, statistically, significant, changes, '(', 'p<0'])]). relacion([sujeto(['Microarray', analysis, of, two, normal, and, seven, breast, cancer, samples]), verbo([found]), complemento([129, genes, with, &, 'gt;fivefold', changes])]). relacion([sujeto(['This', study, demonstrated, that, combined, 'HTA', effectively, narrowed, the, number, of, genes, for, further, 'study,', while]), verbo([retaining]), complemento([the, sensitivity, in, identifying, biologically, important, genes, such, as, 'ERBB2', and, 'ANXA1'])]). relacion([sujeto(['A', distinctive]), verbo([loss]), complemento([of, 'ANXA1', in, breast, cancer, suggests, its, involvement, in, maintaining, normal, breast, biology])]). relacion([sujeto(['BALB/c', mice, immunized, with, 'cruzipain,', a, major, 'Trypanosoma', cruzi, 'antigen,', produce, specific, and, autoreactive, immune, responses, against, heart, 'myosin,']), verbo([associated]), complemento([with, cardiac, functional, and, structural, abnormalities])]). relacion([sujeto(['Preferential', activation, of, the, 'Th2', phenotype, and, an]), verbo([increase]), complemento([in, cell, populations, expressing, 'CD19+,', 'Mac-1+', and, 'Gr-1+', markers, were, found, in, the, spleens, of, these, mice])]). relacion([sujeto(['The', aim, of, the, present, study, was, to, investigate, whether, cardiac, autoimmunity, could, be]), verbo([induced]), complemento([by, cruzipain, immunization, of, 'C57BL/6', mice, and, to, compare, the, immune, response, elicited, with, that, of, 'BALB/c', mice])]). relacion([sujeto(['An']), verbo([increased]), complemento([secretion, of, 'TGFbeta', and, a, greater, number, of, 'CD4+', 'TGFbeta+', cells, were, found, in, immune, 'C57BL/6', but, not, in, 'BALB/c', mice])]). relacion([sujeto(['These', findings, were]), verbo([associated]), complemento([with, the, lack, of, autoreactive, response, against, heart, myosin, and, a, 'myosin-', or, 'cruzipain-derived', peptide])]). relacion([sujeto(['This', function, was]), verbo([suggested]), complemento([to, reflect, the, capacity, of, 'SAP', to, associate, with, 'SLAM', family, receptors, and, enable, tyrosine, phosphorylation, signaling, by, these, receptors, through, 'SAP-mediated', recruitment, of, 'Src-related', kinase, 'FynT'])]). relacion([sujeto(['By', creating, a, mouse, in, which, the, 'FynT']), verbo([binding]), complemento([site, of, 'SAP', was, inactivated, in, the, germ, line, '(', 'sap(R78A)', 'mouse)', and, by, analyzing, mice, lacking, 'SAP,', 'FynT', or, 'SLAM,', evidence, was, obtained, that, the, 'SAP-FynT', cascade, is, indeed, crucial, for, normal, 'T(H)2', functions, in, vitro, and, in, vivo])]). relacion([sujeto(['These', data, imply, that, 'SAP', is, necessary, for, 'T(H)2', cytokine, regulation, primarily, as, a, result, of, its, capacity, to]), verbo([recruit]), complemento(['FynT'])]). relacion([sujeto(['XLP', is]), verbo([caused]), complemento([by, mutations, affecting, 'SAP,', an, adaptor, that, recruits, 'Fyn', to, 'SLAM', family, receptors])]). relacion([sujeto(['SAP-deficient', mice, recapitulate, features, of, 'XLP,', including]), verbo([increased]), complemento(['T', cell, activation, and, decreased, humoral, responses, 'post-infection'])]). relacion([sujeto(['SAP-deficient', 'T', cells, also, show]), verbo([increased]), complemento(['TCR-induced', 'IFN-gamma', and, decreased, 'T(H)2', cytokine, production])]). relacion([sujeto(['We', demonstrate, that, the, defect, in, 'IL-4', secretion, in, 'SAP-deficient', 'T', cells, is, independent, of]), verbo([increased]), complemento(['IFN-gamma', production])]). relacion([sujeto(['SAP-deficient', cells]), verbo([respond]), complemento([normally, to, polarizing, 'cytokines,', yet, show, impaired, 'TCR-mediated', induction, of, 'GATA-3', and, 'IL-4'])]). relacion([sujeto(['Examination', of, 'TCR', signaling, revealed, normal, 'Ca(2+)', mobilization, and, 'ERK', activation, in, 'SAP-deficient', 'cells,', but]), verbo([decreased]), complemento(['PKC-theta', 'recruitment,', 'Bcl-10', 'phosphorylation,', 'IkappaB-alpha', 'degradation,', and, nuclear, 'NF-kappaB1/p50', levels])]). relacion([sujeto(['SLAM', engagement, amplified, 'PKC-theta', recruitment, in, wt, but, not, 'SAP-', or, 'Fyn-deficient', 'cells,', arguing, that, a, 'SAP/Fyn-mediated', pathway]), verbo([enhances]), complemento(['PKC-theta/NF-kappaB1', activation, and, suggesting, a, role, for, this, pathway, in, 'T(H)2', regulation])]). relacion([sujeto(['The', linked, 'IL-4', and, 'IL-13', cytokine, 'genes,', which, are]), verbo([activated]), complemento([and, silenced, in, 'T', helper, '(', 'Th)', 2, and, 'Th1', 'cells,', 'respectively,', are, flanked, by, the, equivalently, expressed, 'RAD50', and, 'KIF3A', genes])]). relacion([sujeto(['A', scan, of, 'DNase', 'I', hypersensitivity, and, 'DNA', methylation, across, approximately, 100, kb, of, the, 'KIF3A/IL-4/IL-13/RAD50', cluster, revealed, differences, in, chromatin, structure, between, 'Th1', and, 'Th2', cells, at, the, 3, '\'', end, of, the, 'RAD50', 'gene,', a, region, previously, shown, to, contain, a, locus, control, region, '(', 'LCR)']), verbo([regulating]), complemento(['Th2-specific', expression, of, 'IL-4', and, 'IL-13'])]). relacion([sujeto(['Naive', 'CD4', 'T', cells, did, not, exhibit, any, 'DNase', 'I', hypersensitivity, in, this, 'region,', but, stimulation, under, either, 'Th1', or, 'Th2', conditions]), verbo([caused]), complemento([rapid, development, of, three, hypersensitive, sites])]). relacion([sujeto(['Our', data, point, to, a, physical, separation, in, the, actions, of, 'STAT6', and, its, downstream, effector, 'GATA3', during, 'Th2', 'differentiation:', 'STAT6', directly, remodels, the, 'RAD50', 'LCR,', whereas, 'GATA3']), verbo([acts]), complemento([only, in, the, vicinity, of, the, 'IL-4', gene])]). relacion([sujeto(['We']), verbo([suggest]), complemento([that, the, 'RAD50', 'LCR', has, a, complex, and, dual, role, in, 'Th1', and, 'Th2', 'differentiation,', communicating, early, 'T', cell, antigen, receptor, and, cytokine, signals, to, the, 'IL-4/IL-13', locus, in, both, differentiating, cell, types])]). relacion([sujeto(['To', determine, the, effect, of, anterior, chamber]), verbo([associated]), complemento([immune, deviation, '(', 'ACAID)', on, 'endotoxin-induced', uveitis, '(', 'EIU)', and, the, possible, mechanism])]). relacion([sujeto(['ACAID', animal, model, was]), verbo([induced]), complemento([by, injection, of, 5, microl, 'IRBP', '(', 10, 'microg/microl)', into, the, anterior, chamber, '(', 'AC)', of, 'Spar-Dawley', '(', 'SD)', rats])]). relacion([sujeto(['While', in, 7, d, 'group,', the, 'DTH', reaction, could, not, be, 'induced,', and, 'IL-10', and, 'GATA-3', expression]), verbo([increased]), complemento([significantly, at, both, the, mRNA, and, protein, levels])]). relacion([sujeto(['The', development, of, 'ACAID', can, reduce, the, ocular, inflammation]), verbo([induced]), complemento([by, 'LPS,', that, is, related, to, the, increase, of, 'GATA-3', and, 'IL-10', expression])]). relacion([sujeto(['Gata2', and, 'Gata3', belong, to, the, 'Gata', family, of, transcription, factors, in, vertebrates, that]), verbo([bind]), complemento([to, a, consensus, &, 'quot;GATA"', 'DNA', sequence])]). relacion([sujeto(['Here,', we]), verbo([have]), complemento([compared, the, expression, patterns, of, 'Gata2', and, 'Gata3', during, normal, inner, ear, development, and, investigated, their, relationship, in, mice, where, either, 'Gata3', or, 'Gata2', has, been, inactivated])]). relacion([sujeto(['Whereas', 'Gata2', is, predominantly]), verbo([expressed]), complemento([in, the, dorsal, vestibular, 'system,', 'Gata3', was, detected, mainly, in, the, ventral, cochlear, duct, and, ganglion])]). relacion([sujeto(['Two', cell, lines]), verbo([expressed]), complemento(['GATA3', but, possessed, intrinsically, different, genetic, programs, under, differentiating, conditions])]). relacion([sujeto(['Under', differentiating, conditions, in, vitro, the, cell, lines]), verbo([expressed]), complemento([very, different, gene, expression, profiles])]). relacion([sujeto(['We']), verbo([suggest]), complemento([that, these, and, other, conditionally, immortal, cell, lines, can, be, used, to, study, transient, events, in, development, against, different, backgrounds, of, cell, competence])]). relacion([sujeto(['Originally', defined, by, their, patterns, of, cytokine, 'production,', 'Th1', and, 'Th2', cells]), verbo([have]), complemento([been, described, more, recently, to, express, other, genes, differentially, as, 'well,', at, least, in, vitro])]). relacion([sujeto(['Th1-polarized', airway, inflammation, was, achieved, by, the, intranasal, instillation, of, adenoviral, vectors, '(', 'Ad)', encoding, 'granulocyte-macrophage', 'colony-stimulating', factor, '(', 'GM-CSF)', and, interleukin, '(', 'IL)-12,', followed, by, daily, aerosolizations, of, 'OVA;', instillation, of, 'Ad/GM-CSF', alone, with, 'OVA', aerosolization]), verbo([led]), complemento([to, 'Th2-polarized', responses])]). relacion([sujeto(['Consistent', with]), verbo([reports]), complemento([from, in, vitro, and, human, 'studies,', mice, undergoing, 'Th1-polarized', inflammation, showed, preferential, expression, of, the, transcription, factor, 't-bet,', the, chemokines, 'IFN-gamma', inducible, protein, '(', 'IP)-10', and, macrophage, inflammatory, protein, 1, alpha, '(', 'MIP-1-alpha),', and, the, chemokine, receptor, 'CCR5'])]). relacion([sujeto(['In', 'contrast,', the, transcription, factor, 'GATA-3,', the, chemokines, 'I-309', and, thymus, and, activation]), verbo([regulated]), complemento([chemokine, '(', 'TARC),', and, the, chemokine, receptors, 'CCR3', and, 'CCR4', were, preferentially, expressed, in, the, 'Th2', model])]). relacion([sujeto([1, was]), verbo([expressed]), complemento([more, strongly, in, the, 'Th1', model, than, in, the, 'Th2', model])]). relacion([sujeto(['These', studies]), verbo([provide]), complemento([a, direct, comparison, of, gene, expression, in, in, vivo, 'Th1-', and, 'Th2-polarized', 'models,', and, demonstrate, that, molecular, events, in, the, lymph, nodes, can, be, altered, fundamentally, by, cytokine, expression, at, distant, mucosal, sites])]). relacion([sujeto(['In', 'T', 'cells,', involvement, of, 'GATA-3', in, cell, 'type-specific', expression, of, the, 'IL-13', gene]), verbo([has]), complemento([been, reported])]). relacion([sujeto(['However,', the, mechanisms, that]), verbo([induce]), complemento([rapid, transactivation, of, the, 'IL-13', gene, in, response, to, various, types, of, stimulation, have, hitherto, remained, unknown])]). relacion([sujeto(['In', this, 'report,', we, describe, our, investigation, of, the, promoter, region, necessary, for, 'IL-13', 'transcription;', we]), verbo([have]), complemento([found, that, both, 'AP-1', and, 'GATA', proteins, are, indispensable, for, 'IL-13', transcription, in, mouse, mast, cells])]). relacion([sujeto(['Transfection', experiments]), verbo([have]), complemento([revealed, that, 'GATA-1', and, 'GATA-2', proteins, are, able, to, associate, with, 'AP-1', proteins])]). relacion([sujeto(['We']), verbo([have]), complemento([also, shown, that, overexpression, of, 'GATA-1', induced, excess, 'AP-1', binding, to, the, 'IL-13', promoter, as, well, as, a, significant, increase, in, 'IL-13', production, in, mast, cells])]). relacion([sujeto(['The', results, of, the, present, study]), verbo([have]), complemento([shown, that, direct, interaction, between, 'AP-1', and, 'GATA', proteins, plays, an, important, role, in, 'IL-13', transcription, in, mast, cells])]). relacion([sujeto(['In', this, 'study,', we, demonstrate, that, the, 'T', cell, inhibitor, placental, protein, 14, '(', 'PP14;', 'glycodelin)', preferentially]), verbo([inhibits]), complemento(['Th1', cytokine, responses, and, chemokine, expression, when, present, during, ex, vivo, priming, of, 'CD4+', 'T', cells])]). relacion([sujeto(['CD4', 'T', cell, differentiation, is, a, complex, process, affected, by, many, transcription, factors]), verbo([interacting]), complemento([in, a, tightly, regulated, manner])]). relacion([sujeto(['We']), verbo([have]), complemento([previously, shown, that, 'CIITA-deficient', mouse, 'Th1', cells, expressed, 'Th2-type', 'cytokines,', while, 'IFN-gamma', expression, was, normal])]). relacion([sujeto(['CIITA-deficient', 'Th1', cells]), verbo([require]), complemento(['TCR-mediated', signaling, to, express, 'Th2', 'cytokines,', and, this, occurs, with, similar, kinetics, as, 'wild-type', 'Th2', cells])]). relacion([sujeto(['Both', 'GATA-3', and, 'IL-4', appear, to, be]), verbo([required]), complemento([for, 'CIITA-deficient', 'Th1', cells, to, express, 'Th2-type', cytokines])]). relacion([sujeto(['It']), verbo([activates]), complemento([the, transcription, factors, of, various, cellular, genes, and, interacts, with, cellular, proteins])]). relacion([sujeto(['Implications', for, the, significance, of, 'GATA3', in, 'T-cell', development, and, 'function,', 'T', helper2, '(', 'Th2)', 'differentiation,', and, a, role, of, 'GATA3', during, the, immune, response]), verbo([have]), complemento([been, reported])]). relacion([sujeto(['This', interaction, may, be]), verbo([involved]), complemento([in, the, pathophysiology, of, adult, 'T-cell', 'leukemia/lymphoma', '(', 'ATL)', and, tropical, spastic, 'paraparesis/HTLV-I-associated', myelopathy, '(', 'TSP/HAM)'])]). relacion([sujeto(['To', address, how, heritable, patterns, of, gene, expression, are, acquired, during, the, differentiation, of, 'Th1', and, 'Th2', 'cells,', we, analyzed, the]), verbo([nuclear]), complemento([position, of, 'lineage-restricted', cytokine, genes, and, their, upstream, regulators, by, 3, -, dimensional, fluorescence, in, situ, hybridization])]). relacion([sujeto(['During', 'Th1', 'differentiation,', 'GATA-3', and, 'c-maf', 'loci,', which, encode, upstream, regulators, of, 'Th2', 'cytokines,', were, progressively, repositioned, to, centromeric, heterochromatin, as, defined, by, a, 'gamma-satellite', repeat, probe, 'and/or', the]), verbo([nuclear]), complemento(['periphery,', compartments, that, have, been, associated, with, transcriptional, repression])]). relacion([sujeto(['In', 'contrast,', we, did, not]), verbo([find]), complemento([repositioning, of, the, cytokine, gene, loci, 'IL-2,', 'IL-3,', 'IL-4', or, 'IFN-gamma', during, 'T', helper, cell, differentiation])]). relacion([sujeto(['Instead,', 'IFN-gamma', was, constitutively]), verbo([associated]), complemento([with, the, nuclear, 'periphery,', even, when, primed, for, expression, in, 'Th1', cells])]). relacion([sujeto(['Our', results]), verbo([suggest]), complemento([that, 'Th1/Th2', lineage, commitment, and, differentiation, involve, repositioning, of, the, regulators, of, cytokine, 'expression,', rather, than, the, cytokine, genes, themselves])]). relacion([sujeto(['To', review, potential, or, current, therapies, that]), verbo([decrease]), complemento(['IgE', synthesis, or, effects])]). relacion([sujeto(['Transcription', factors, may, be, altered, to, differentiate, lymphocytes, into, a, 'TH1', 'phenotype,', thus]), verbo([decreasing]), complemento(['TH2-driven', 'IgE', production])]). relacion([sujeto(['This', may, be, accomplished, by]), verbo([inhibiting]), complemento(['GATA-3', with, peroxisome, 'proliferator-activated', receptor, agonists, or, promoting, 'T-bet', expression, with, 'CpG', motifs])]). relacion([sujeto(['Cytokine', therapy, with, 'anti-IL-4', or, 'anti-IL-13']), verbo([has]), complemento([the, potential, to, directly, influence, 'IgE-mediated', 'diseases,', but, strategies, aimed, at, 'IL-4', alone, have, been, disappointing])]). relacion([sujeto(['Clinical', trials, with, 'interferon-gamma', or, 'IL-12,', 2, cytokines, important, in]), verbo([promoting]), complemento(['TH1', and, inhibiting, 'TH2', 'responses,', have, been, fraught, with, adverse, effects, that, make, their, use, limited])]). relacion([sujeto(['The', use, of, plasmids, encoding, 'interferon-gamma', or, 'IL-12']), verbo([has]), complemento([shown, promise, in, animal, models])]). relacion([sujeto(['Inhibition', of, 'IgE', synthesis]), verbo([has]), complemento([been, demonstrated, with, 'anti-CD23', antibodies])]). relacion([sujeto(['Early', human, studies]), verbo([have]), complemento([been, very, 'encouraging,', and, larger, studies, are, under, way])]). relacion([sujeto(['Expression', of, the, transcription, factor, 'GATA-3', is, strongly]), verbo([associated]), complemento([with, 'T', helper, type, 2, '(', 'T(H)2)', 'differentiation,', but, genetic, evidence, for, its, involvement, in, this, process, has, been, lacking])]). relacion([sujeto(['NKT', cells, produce, large, amounts, of, cytokines]), verbo([associated]), complemento([with, both, the, 'Th1', '(', 'IFN-gamma)', and, 'Th2', '(', 'IL-4)', responses, following, stimulation, of, their, invariant, 'Valpha14', 'Ag', receptor])]). relacion([sujeto(['Intriguingly,', 'LFA-1-/-', mice, showed]), verbo([increased]), complemento(['IL-4,', 'IL-5,', and, 'IL-13', production, and, polarized, 'Th2-type', responses, in, response, to, 'alpha-GalCer', in, vitro, and, in, vivo])]). relacion([sujeto(['These', results]), verbo([provide]), complemento([the, first, genetic, evidence, that, the, adhesion, receptor, 'LFA-1', has, a, crucial, role, in, 'Th2-polarizing', functions, of, 'NKT', cells])]). relacion([sujeto(['Freshly', prepared, 'NK', cells]), verbo([express]), complemento(['IL-2Rbeta,', 'IL-2RgammaC,', and, 'IL-4Ralpha'])]). relacion([sujeto(['After', stimulation, with, 'PMA', and, 'ionomycin,', 'NK', cells]), verbo([expressed]), complemento(['IL-2Ralpha'])]). relacion([sujeto(['NK1', cells, displayed, higher, cytotoxic, activity, against, 'Yac-1']), verbo([target]), complemento([cells])]). relacion([sujeto(['Both', 'NK1', and, 'NK2', cells]), verbo([expressed]), complemento([large, amounts, of, repressor, of, 'GATA,', the, levels, of, which, were, equivalent, to, 'CD8', 'Tc1', and, 'Tc2', cells, and, significantly, higher, than, those, in, 'Th2', cells])]). relacion([sujeto(['The', production, of, 'IL-5', and, 'IL-13', in, 'NK2', cells, was]), verbo([found]), complemento([to, be, 'STAT6', dependent])]). relacion([sujeto(['Differentiation', of, uncommitted, 'T', cells, into, 'Th1', and, 'Th2', subpopulations, depends, on, both, intracellular, events, controlling, expression, of, transcription, factors, 'T-bet', and, 'GATA-3', and, interactions, between, cells]), verbo([mediated]), complemento([by, 'cytokines,', particularly, 'IL4', and, 'IFNgamma'])]). relacion([sujeto(['A', great, deal, is, known, about, the, intracellular, and, extracellular, events]), verbo([involved]), complemento([in, 'Th1', and, 'Th2', '(', 'Th)', 'differentiation,', but, how, these, are, integrated, in, 'T-cell', populations, or, indeed, why, extracellular, cytokine, control, is, required, after, a, decision, has, been, made, at, a, transcriptional, level, is, not, at, all, understood])]). relacion([sujeto(['After', transient, signalling, by, 'APC,', continued, 'Th1', and, 'Th2', differentiation, is, shown, to]), verbo([require]), complemento([cytokine, production, by, the, proliferating, 'T', cells])]). relacion([sujeto(['Moreover,', intercellular, communication, by, 'T-cell-derived', cytokines, lowers, the, threshold, of, 'APC', signals]), verbo([required]), complemento([for, 'Th', differentiation])]). relacion([sujeto(['This']), verbo([provides]), complemento([an, explanation, for, enhanced, 'Th', differentiation, by, 'pre-existing', memory, 'T', cells])]). relacion([sujeto(['It']), verbo([suggests]), complemento([a, mechanism, for, switching, between, 'Th1', and, 'Th2', in, the, 'so-called', irreversible, state, that, may, be, developed, as, a, novel, therapeutic, means, of, manipulating, 'Th1', and, 'Th2', responses])]). relacion([sujeto(['Exogenous', expression, of, the, transcription, factor, 'Scl', '(', 'Tal1)', in, 'WEHI-3B', 'D+', myelomonocytic, leukemia, cells, interferes, with, their, capacity, to]), verbo([respond]), complemento([to, 'all-trans', retinoic, acid, '(', 'ATRA)', induced, 'differentiation;', combination, of, 'ATRA', with, 'LiCl,', 'however,', circumvents, the, inhibition, of, differentiation, produced, by, 'Scl'])]). relacion([sujeto(['To']), verbo([gain]), complemento([information, on, the, possible, involvement, of, this, transcription, factor, in, the, 'non-responsiveness', of, acute, myelocytic, leukemia, '(', 'AML)', patients, to, 'ATRA,', we, compared, the, endogenous, expression, levels, of, 'Scl', and, its, transcription, complex, partners, '[', i])]). relacion([sujeto(['ATRA', produced, changes, in, at, least, one, surface, antigen, differentiation, marker, in, 89, '%', of, patient, 'blasts,', while, 'LiCl']), verbo([caused]), complemento([such, changes, in, 72, '%', of, the, leukemic, cells, of, patients])]). relacion([sujeto(['The', combination, of, 'LiCl', and, 'ATRA']), verbo([induced]), complemento([the, differentiation, of, leukemic, blasts, from, 94, '%', of, patients])]). relacion([sujeto(['Although', the, expression, of, the, transcription, factors, did, not]), verbo([act]), complemento([as, individual, predictors, of, responsiveness, or, 'non-responsiveness', to, the, inducers, of, 'differentiation,', 'ATRA', or, 'ATRA', plus, 'LiCl,', the, addition, of, 'LiCl', to, 'ATRA', increased, the, differentiation, response, over, that, of, 'ATRA', alone, in, a, number, of, leukemic, samples])]). relacion([sujeto(['These', findings]), verbo([suggest]), complemento([that, the, combination, of, 'LiCl', and, 'ATRA', may, produce, some, clinical, benefit, in, the, treatment, of, the, myeloid, leukemias])]). relacion([sujeto(['Using', the, chromosome, conformation, capture, 'technique,', we]), verbo([found]), complemento([that, in, 'T', 'cells,', natural, killer, 'cells,', 'B', cells, and, 'fibroblasts,', the, promoters, for, the, genes, encoding, 'T(H)2', cytokines, are, located, in, close, spatial, 'proximity,', forming, an, initial, chromatin, core, configuration])]). relacion([sujeto(['In', 'CD4(+)', 'T', cells, and, natural, killer, 'cells,', but, not, 'B', cells, and, 'fibroblasts,', the, 'T(H)2', locus, control, region]), verbo([participates]), complemento([in, this, configuration])]). relacion([sujeto(['Although', a, number, of, transcription, factors, '(', 'TFs)']), verbo([have]), complemento([been, identified, that, play, a, pivotal, role, in, the, development, of, hematopoietic, 'lineages,', only, little, is, known, about, factors, that, may, influence, development, and, lineage, commitment, of, natural, killer, '(', 'NK)', or, 'NK-like', 'T', '(', 'NKT)-cells'])]). relacion([sujeto(['AML1,', 'E2A,', 'ETS1,', 'IKAROS', and, 'IRF1', were]), verbo([found]), complemento([to, be, positive, for, all, cell, lines, tested, whereas, 'GATA1', turned, out, to, be, universally, negative])]). relacion([sujeto(['These', mutations, cluster, in, the, vicinity, of, the, highly]), verbo([conserved]), complemento([second, 'zinc-finger', that, is, required, for, 'DNA', binding])]). relacion([sujeto(['In', addition, to, these, 'five,', we, identified, using, cDNA, sequencing, a, unique, 'mis-splicing', variant, that]), verbo([caused]), complemento([a, frameshift, mutation])]). relacion([sujeto(['One', of, the, somatic, mutations, we, identified, was, identical, to, a, germline, 'GATA3', mutation]), verbo([reported]), complemento([in, two, kindreds, with, 'HDR', 'syndrome/OMIM', #, 146255, ',', which, is, an, autosomal, dominant, syndrome, caused, by, the, 'haplo-insufficiency', of, 'GATA3'])]). relacion([sujeto(['The', ectopic, expression, of, 'GATA3', in, human, 293, 'T', cells]), verbo([caused]), complemento([the, induction, of, 73, genes, including, six, 'cytokeratins,', and, inhibited, cell, line, doubling, times])]). relacion([sujeto(['These', data]), verbo([suggest]), complemento([that, 'GATA3', is, involved, in, growth, control, and, the, maintenance, of, the, differentiated, state, in, epithelial, 'cells,', and, that, 'GATA3', variants, may, contribute, to, tumorigenesis, in, 'ESR1-positive', breast, tumors])]). relacion([sujeto(['Stromal', 'OP9', cells, ectopically]), verbo([expressing]), complemento([the, 'Notch', ligand, 'Delta-like1', mimic, the, thymic, environment, by, inducing, hemopoietic, stem, cells, to, undergo, in, vitro, 'T', cell, development])]). relacion([sujeto(['Notch1', is, also]), verbo([expressed]), complemento([on, 'Pax5-/-', 'pro-B', 'cells,', which, are, clonable, lymphoid, progenitors, with, a, latent, myeloid, potential])]). relacion([sujeto(['In', vitro, 'T', cell, development, of, 'Pax5-/-', progenitors, strictly, depends, on, 'Notch1', function, and, progresses, through, normal, developmental, stages, by]), verbo([expressing]), complemento(['T', cell, markers, and, rearranging, 'TCRbeta,', 'gamma,', and, delta, loci, in, the, correct, temporal, sequence])]). relacion([sujeto(['Notch-stimulated', 'Pax5-/-', progenitors, efficiently, 'down-regulate', the, expression, of, 'B', 'cell-specific', 'genes,', consistent, with, a, role, of, 'Notch1', in]), verbo([preventing]), complemento(['B', lymphopoiesis, in, the, thymus])]). relacion([sujeto(['At', the, same, 'time,', 'Notch', signaling, rapidly]), verbo([induces]), complemento([cell, surface, expression, of, the, 'c-Kit', receptor, and, transcription, of, the, target, genes, 'Deltex1', and, 'pre-Talpha', concomitant, with, the, activation, of, 'TCR', 'Vbeta', germline, transcription, and, the, regulatory, genes, 'GATA3', and, 'Tcf1'])]). relacion([sujeto(['These', data]), verbo([suggest]), complemento([that, 'Notch1', acts, upstream, of, 'GATA3', and, 'Tcf1', in, early, 'T', cell, development, and, regulates, 'Vbeta-DJbeta', rearrangements, by, controlling, the, chromatin, accessibility, of, 'Vbeta', genes, at, the, 'TCRbeta', locus])]). relacion([sujeto(['Chromosome', 10, p, terminal, deletions]), verbo([have]), complemento([been, associated, with, a, 'DiGeorge', like, phenotype])]). relacion([sujeto(['Van', 'Esch', '(', 2000, ')', identified, in, a, 'HDR', 'patient,', within, a, 200, kb, critical, 'region,', the, 'GATA3', 'gene,', a, transcription, factor]), verbo([involved]), complemento([in, the, embryonic, development, of, the, 'parathyroids,', auditory, system, and, kidneys])]). relacion([sujeto(['We', describe, a, new, male, 'patient,', 33, -, 'year-old,', with, 10, p, partial, deletion, affected, by, 'hypocalcemia,', basal, ganglia, calcifications, and, a, severe, autistic, syndrome]), verbo([associated]), complemento([with, mental, retardation])]). relacion([sujeto(['Neurologically']), verbo([he]), complemento([presented, severe, impairment, of, 'language,', 'hypotonia,', clumsiness, and, a, postural, dystonic, attitude])]). relacion([sujeto(['GATA3']), verbo([has]), complemento([been, found, to, regulate, the, development, of, serotoninergic, neurons])]). relacion([sujeto(['Here,', we]), verbo([have]), complemento([studied, the, function, of, 'Gata2', and, 'Gata3', 'zinc-finger', transcription, factors, in, autonomic, neuron, development])]). relacion([sujeto(['In', the, 'chick,', 'Gata2', but, not, 'Gata3', is]), verbo([expressed]), complemento([in, developing, sympathetic, precursor, cells])]). relacion([sujeto(['Gata2', expression, starts, after, 'Mash1,', 'Phox2b,', 'Hand2', and, 'Phox2a', 'expression,', but, before, the, onset, of, the, noradrenergic, marker, genes, 'Th', and, 'Dbh,', and, is]), verbo([maintained]), complemento([throughout, development])]). relacion([sujeto(['Loss-of-function', experiments, resulted, in, a, strong, reduction, in, the, size, of, the, sympathetic, chain, and, in]), verbo([decreased]), complemento(['Th', expression])]). relacion([sujeto(['Erythropoietin', '(', 'Epo)', gene, expression, is, under, the, control, of, 'hypoxia-inducible', factor, 1, '(', 'HIF-1),', and, is, negatively]), verbo([regulated]), complemento([by, 'GATA'])]). relacion([sujeto(['Interleukin', 1, beta, '(', 'IL-1beta)', and, tumor, necrosis, factor, alpha, '(', 'TNF-alpha),', which]), verbo([increase]), complemento([the, binding, activity, of, 'GATA', and, inhibit, 'Epo', promoter, 'activity,', are, increased, in, patients, with, anemia, of, chronic, disease, '(', 'ACD)'])]). relacion([sujeto(['We', previously, demonstrated, the, ability, of, 'K-7174', '(', a, 'GATA-specific', 'inhibitor),', when, injected, 'intraperitoneally,', to, improve, 'Epo', production, that, had, been]), verbo([inhibited]), complemento([by, 'IL-1beta', or, 'TNF-alpha', treatment])]). relacion([sujeto(['In', the, present, 'study,', we, examined, the, ability, of, both, 'K-11706,', which]), verbo([inhibits]), complemento(['GATA', and, enhances, 'HIF-1', binding, 'activity,', and, 'K-13144,', which, has, no, effect, on, 'GATA', or, 'HIF-1', binding, 'activity,', to, improve, 'Epo', production, following, inhibition, by, 'IL-1beta', or, 'TNF-alpha', in, 'Hep3B', cells, in, vitro, and, in, an, in, vivo, mouse, assay])]). relacion([sujeto(['Oral', administration, of, 'K-11706', reversed, the]), verbo([decreases]), complemento([in, hemoglobin, and, serum, 'Epo', 'concentrations,', reticulocyte, 'counts,', and, numbers, of, erythroid, 'colony-forming', units, '(', 'CFU-Es)', induced, by, 'IL-1beta', or, 'TNF-alpha'])]). relacion([sujeto(['The', active, metabolite, of, vitamin, 'D', '(', 1, ',', 25, -, dihydroxyvitamin, 'D(3)', '(', 1, ',', 25, '(', 'OH)(2)D(3)))', is, known, to]), verbo([modulate]), complemento([the, immune, response, in, 'Th1', 'cell-directed', diseases])]). relacion([sujeto(['To', investigate, the, role, of, vitamin, 'D', in, 'Th2', 'cell-directed', 'diseases,', experimental, allergic, asthma, was]), verbo([induced]), complemento([in, vitamin, 'D', receptor, '(', 'VDR)', knockout, and, in, 'wild-type', '(', 'WT)', mice])]). relacion([sujeto(['The', only, discernable, effect, of, 1, ',', 25, '(', 'OH)(2)D(3)', on, experimental, allergic, asthma, in, 'WT', mice, was, an]), verbo([increased]), complemento([expression, of, two, 'Th2-related', genes, '(', soluble, 'CD23', and, 'GATA-3)', in, lungs, of, 'BALB/c', mice, exposed, to, 'Ag', through, the, nasal, route, only])]). relacion([sujeto(['The', data]), verbo([suggest]), complemento([that, although, 1, ',', 25, '(', 'OH)(2)D(3)', induced, these, 'Th2-type', 'genes,', the, treatment, failed, to, have, any, affect, on, experimental, asthma, severity])]). relacion([sujeto(['However,', 'VDR-deficient', mice, failed, to, develop, experimental, allergic, 'asthma,']), verbo([suggesting]), complemento([an, important, role, for, the, vitamin, 'D', endocrine, system, in, the, generation, of, 'Th2-driven', inflammation, in, the, lung])]). relacion([sujeto(['The', retina, is, a, neural, tissue, especially, differentiated, for, vision, 'and,', 'thus,', the, inner, 'blood-retinal', barrier, '(', inner, 'BRB)', specific, molecules, may, play, an, essential, role, in]), verbo([maintaining]), complemento([neural, functions, in, the, retina])]). relacion([sujeto(['The', purpose, of, the, present, study, was, to, identify, selectively]), verbo([expressed]), complemento([genes, at, the, inner, 'blood-retinal', barrier, compared, with, the, 'blood-brain', barrier, '(', 'BBB)'])]). relacion([sujeto(['A', comparison, of]), verbo([expressed]), complemento([genes, between, conditionally, immortalized, rat, retinal, '(', 'TR-iBRB)', cell, lines, and, brain, capillary, endothelial, '(', 'TR-BBB)', cell, lines, was, performed, using, mRNA, differential, display, analysis, and, quantitative, real, time, 'PCR', analysis])]). relacion([sujeto(['Eight', clones, were, identified, as, highly]), verbo([expressed]), complemento([genes, in, 'TR-iBRB', cells, including, 'GATA-binding', 'protein-3', '(', 'GATA-3),', cytosolic, branched, chain, amino, transferase, '(', 'BCATc),', and, 'M-cadherin', '(', 'cadherin-15)'])]). relacion([sujeto(['The', rat, 'M-cadherin', gene, was, cloned, from, 'TR-iBRB', 'cells,', for, the, first, 'time,', and]), verbo([has]), complemento([&, 'gt;86%', amino, acid, sequence, identity, to, the, previously, cloned, mammalian, 'M-cadherins'])]). relacion([sujeto(['M-cadherin,', 'GATA-3,', and, 'BCATc', are, highly]), verbo([expressed]), complemento([in, 'TR-iBRB', cells, compared, with, 'TR-BBB', cells, and, may, indeed, be, involved, in, unique, functions, at, the, inner, 'BRB'])]). relacion([sujeto(['These', structural, changes, are, preceded, by, aberrant, expansion, of, proximal, first, arch, gene, expression, into, the, distal, 'arch,', in, addition, to, the, previously, described]), verbo([loss]), complemento([of, a, 'Dlx6/Hand2', expression, network])]). relacion([sujeto(['Although', this, distal, expression, is, not, dependent, on, either, 'Ednra', or, 'Dlx5/Dlx6', 'function,', it, may]), verbo([require]), complemento([one, or, more, 'GATA', factors])]). relacion([sujeto(['Together,', our, results]), verbo([suggest]), complemento([that, the, establishment, of, a, '\'', mandibular, 'identity\'', during, lower, jaw, development, requires, both, 'Ednra-dependent', and, -, independent, signaling, pathways])]). relacion([sujeto(['HDR', syndrome, is, a, newly]), verbo([recognized]), complemento([very, rare, syndrome, defined, by, the, combination, of, 'hypoparathyroidism,', renal, dysplasia, and, sensorineural, deafness])]). relacion([sujeto(['Here', we]), verbo([report]), complemento([a, 16, 'year-old', girl, with, 'HDR', syndrome, who, presented, with, generalized, 'psoriasis,', which, is, an, unusual, presentation])]). relacion([sujeto(['It', is]), verbo([suggested]), complemento([that, generalized, psoriasis, might, have, been, induced, by, hypocalcemia, due, to, hypoparathyroidism, associated, with, 'HDR', syndrome])]). relacion([sujeto(['To', study, interferon, gamma, '(', 'IFN', 'gamma)', production, and, the, expression, of, 'T-bet', and, 'GATA-3,', the, transcription, factors]), verbo([associated]), complemento([with, 'Th1', and, 'Th2,', in, peripheral, blood, mononuclear, cells, '(', 'PBMC)', from, patients, with, rheumatoid, arthritis, before, and, during, infliximab, 'treatment,', so, as, to, distinguish, between, a, disease, specific, and, a, disease, activity, dependent, defect])]). relacion([sujeto(['A', reduction, in, spontaneous, 'IFN', gamma, production, and, in, the, response, to, 'Th1']), verbo([inducing]), complemento([cytokines, occurred, in, rheumatoid, 'PBMC'])]). relacion([sujeto(['Reduction', of, systemic, inflammation, with, infliximab, treatment]), verbo([increased]), complemento(['IFN', gamma, production, in, response, to, 'IL12', or, 'IL12+IL18'])]). relacion([sujeto(['The', 'IFN', 'gamma/IL4', expression, ratio, of, rheumatoid, blood, before, treatment, was, lower, than, in, healthy, controls, but, was]), verbo([increased]), complemento([by, infliximab, treatment])]). relacion([sujeto(['The', 'IFN', 'gamma/IL4', ratio, might]), verbo([express]), complemento([the, blood, 'Th1/Th2', balance, better, than, the, 'T-bet/GATA-3', ratio])]). relacion([sujeto(['In', the, present, 'study,', we]), verbo([have]), complemento([investigated, the, development, of, serotonergic, neurons, in, the, zebrafish])]). relacion([sujeto(['Unlike', two, other, zebrafish, tph, genes, '(', tphD1, and, 'tphD2),', tphR, is]), verbo([expressed]), complemento([in, serotonergic, raphe, 'neurons,', similar, to, tph, genes, in, mammalian, species])]). relacion([sujeto([tphR, is, also]), verbo([expressed]), complemento([in, the, pineal, organ, where, it, is, likely, to, be, involved, in, the, pathway, leading, to, synthesis, of, melatonin])]). relacion([sujeto(['To', better, understand, the, signaling, pathways]), verbo([involved]), complemento([in, the, induction, of, the, serotonergic, 'phenotype,', we, analyzed, tphR, expression, and, 5, 'HT-IR', in, embryos, in, which, either, 'Hh', or, 'Fgf', signals, are, abrogated])]). relacion([sujeto([1, ',', which]), verbo([regulates]), complemento([expression, of, 'ace/fgf8,', and, probably, other, genes, encoding, signaling, proteins])]). relacion([sujeto(['Similarly,', serotonergic, raphe, neurons, are, absent, in, embryos, lacking, 'Hh', activity, confirming, a]), verbo([conserved]), complemento([role, for, 'Hh', signals, in, the, induction, of, these, cells])]). relacion([sujeto(['Conversely,', 'over-activation', of, the, 'Hh', pathway]), verbo([increases]), complemento([the, number, of, serotonergic, neurons])]). relacion([sujeto([2, and, 'Gata3']), verbo([acting]), complemento([downstream, of, 'Hh', activity, in, the, development, of, serotonergic, raphe, neurons])]). relacion([sujeto(['Our', results, show, that, the, pathways]), verbo([involved]), complemento([in, induction, of, hindbrain, serotonergic, neurons, are, likely, to, be, conserved, in, all, vertebrates, and, help, establish, the, zebrafish, as, a, model, system, to, study, this, important, neuronal, class])]). relacion([sujeto(['By', 'real-time', 'PCR,', 'IFN-gamma', mRNA, levels, in, peripheral, blood, mononuclear, cells, '(', 'PBMNC)', were, significantly]), verbo([decreased]), complemento([in, 'Kawasaki', disease, patients, compared, with, those, with, 'measles,', and, tended, to, be, lower, than, those, in, healthy, controls])]). relacion([sujeto(['T-bet', mRNA, levels, were, significantly]), verbo([decreased]), complemento([in, patients, with, 'Kawasaki', disease, compared, with, healthy, controls])]). relacion([sujeto(['In', 'addition,', 'IL-4', and, 'GATA-3', mRNA, levels, were, significantly]), verbo([decreased]), complemento([in, 'Kawasaki', disease, compared, with, healthy, controls])]). relacion([sujeto(['Regulatory', cytokine, mRNA, levels, '(', 'TGF-beta', and, 'IL-10)', were, also]), verbo([decreased]), complemento([in, 'Kawasaki', disease])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, the, suppressed, function, of, 'Th1', and, 'Th2,', associated, with, the, suppression, of, both, 'T-bet', and, 'GATA-3', gene, 'expression,', may, be, one, of, the, immunological, characteristics, of, 'Kawasaki', disease])]). relacion([sujeto(['The', role, of, 'Stat6', '(', signal, transducers, and, activators, of, 'transcription)', in, the, recruitment, and, activation, of, eosinophils]), verbo([has]), complemento([been, studied, in, detail, in, asthma, and, other, allergic, diseases])]). relacion([sujeto(['Prominent', blood, and, intestinal, eosinophilia, were]), verbo([induced]), complemento([after, day, 14, postinfection, '(', p])]). relacion([sujeto([')', and]), verbo([maintained]), complemento([at, this, level, in, 'Stat6(-/-)', 'mice,', whereas, in, 'wild-type', mice, eosinophil, responses, reached, a, peak, on, day, 10, p])]). relacion([sujeto([brasiliensis, into, 'wild-type', mice]), verbo([induced]), complemento([rapid, and, exaggerated, 'eosinophilia,', whereas, secondary, infection, in, 'Stat6(-/-)', mice, resulted, in, almost, the, same, eosinophil, responses, as, those, of, the, primary, 'infection,', suggesting, a, lack, of, memory, responses])]). relacion([sujeto(['Blood', eosinophilia, was, also]), verbo([induced]), complemento([in, 'Stat6(-/-)', mice, implanted, with, 'N'])]). relacion([sujeto([brasiliensis, in, the, small, 'intestine,']), verbo([suggesting]), complemento([that, intestinal, exposure, to, parasitic, antigen, is, sufficient, to, induce, eosinophil, responses])]). relacion([sujeto(['Furthermore,', this, prominent, eosinophil, response, of, 'Stat6(-/-)', mice, after, day, 14, was, closely]), verbo([associated]), complemento([with, an, increase, of, interleukin, '(', 'IL)-5', production, in, serum, and, intestine])]). relacion([sujeto(['Neither', 'IL-4', nor, eotaxin, were, significantly]), verbo([induced]), complemento([in, 'Stat6(-/-)', mice, after, infection, with, 'N'])]). relacion([sujeto(['We', also]), verbo([found]), complemento([that, mRNA, for, 'IL-5,', 'GATA-3', and, eosinophil, peroxidase, '(', 'EPO)', are, induced, in, the, intestine, of, 'Stat6(-/-)', mice, on, day, 14, p])]). relacion([sujeto(['Taken', 'together,', these, results]), verbo([provide]), complemento([evidence, for, 'Stat6-independent', 'IL-5', production, and, subsequent, eosinophil, responses, after, chronic, infection, with, 'N'])]). relacion([sujeto(['The', differentiation, of, helper, 'T', '(', 'Th)', lymphocytes, during, the, immune, response]), verbo([has]), complemento([been, shown, to, occur, along, alternative, pathways, designated, as, 'Th1', and, 'Th2'])]). relacion([sujeto(['Induction', of, the, 'Th1', and, 'Th2', pathways, is]), verbo([associated]), complemento([with, the, conversely, regulated, expression, of, the, master, factors, 'T-bet', and, 'GATA-3,', respectively])]). relacion([sujeto(['We', develop, mathematical, models, of, the, underlying, regulatory, networks, to]), verbo([provide]), complemento([a, framework, for, the, analysis, of, experimental, data])]). relacion([sujeto(['This', system, works, as, a, bistable, switch, that, enables, the]), verbo([triggering]), complemento([of, a, differentiation, program, by, transient, inductive, signals])]). relacion([sujeto(['GATA-3', inhibitors, '(', such, as, 'FOG-1', and, 'ROG)']), verbo([modulate]), complemento(['GATA-3', expression, by, yet, unidentified, mechanisms])]). relacion([sujeto(['Three', potential, modes, of, 'inhibition,', sequestration, by, a]), verbo([binding]), complemento(['protein,', repression, of, basal, 'transcription,', and, repression, of, 'autoactivation,', are, predicted, to, have, 'distinct,', and, strongly, 'concentration-dependent,', regulatory, effects, on, 'GATA-3', dynamics])]). relacion([sujeto(['IL-4', was, not]), verbo([required]), complemento([to, maintain, the, capability, for, 'Th2', cytokine, production, in, in, vivo, generated, 'antigen-specific', memory, 'Th2', cells])]). relacion([sujeto(['Histone', 'H3-K9/14', hyperacetylation, and, intergenic, transcripts]), verbo([associated]), complemento([with, the, 'IL-4', gene, locus, were, preserved, in, the, absence, of, 'IL-4,', but, those, associated, with, the, 'IL-13', gene, were, partially, 'IL-4-dependent'])]). relacion([sujeto(['Thus,', memory, 'Th2', cells]), verbo([maintain]), complemento([a, unique, 'Th2-specific', remodeled, chromatin, in, the, 'IL-4', and, 'IL-13', gene, loci, by, active, molecular, events, that, are, 'IL-4-independent'])]). relacion([sujeto(['The', concentration, of, 'INF-gamma', was, higher, in, atopic, subjects, than, in, 'non-atopic', subjects, '[', '(', 618, +, /, -, 89, ')', micro, 'g/L', vs, '(', 680, +, /, -, 83, ')', 'microg/L,', 'P', &, 'lt;', 0.01, ']', ',', but, no, difference, was]), verbo([found]), complemento([between, adults, and, children])]). relacion([sujeto(['The', levels, of, 'GATA-3', mRNA, expression, were, 0.43, +, /, -, 0.07, in, asthma, and, 0.29, +, /, -, 0.09, in, the, control, '(', 'P', &, 'lt;', 0.01, ')', ',', 'however,', no, differences, were]), verbo([found]), complemento([between, atopic, and, 'non-atopic,', children, and, adults, '(', 0.5, +, /, -, 0.12, vs, 0.4, +, /, -, 0.1, ',', 0.44, +, /, -, 0.09, vs, 0.43, +, /, -, 0.07, ',', 'respectively,', 'P', &, 'gt;', 0.05, ')'])]). relacion([sujeto(['A', positive, correlation, was]), verbo([found]), complemento([between, concentration, of, 'INF-gamma', and, 'T-bet', mRNA, level, '(', 'r=0'])]). relacion([sujeto(['Considering', the, fact, that, committed, 'Th2', cells, underwent, 're-differentiation']), verbo([induced]), complemento([by, 'T-bet,', this, novel, 'Th1-specific', transcription, factor, is, a, fascinating, target, gene, for, modifying, to, restore, the, 'Th1', and, 'Th2', balance])]). relacion([sujeto(['The', regulatory, mechanism, by, which, 'GATA-3']), verbo([suppresses]), complemento(['IFN-gamma', gene, expression, was, investigated])]). relacion([sujeto(['A', reduction, of, 'GATA-3', using, 'RNA', interference, technology, 'enhanced,', whereas, overexpression, of, 'GATA-3']), verbo([suppressed]), complemento(['IFN-gamma', mRNA, expression])]). relacion([sujeto(['Two', 'GATA', elements, located, in, the, 'cis-regulatory', elements, did, not, contribute, to, the, suppression, of, 'IFN-gamma', promoter, 'activity,', even, though, they, behaved, as]), verbo([binding]), complemento([sites, for, 'GATA-3'])]). relacion([sujeto(['Among', several, transcription, factors, putatively]), verbo([interacting]), complemento([with, this, 'region,', 'Stat4,', which, enhanced, 'IFN-gamma', promoter, 'activity,', was, 'down-regulated', by, 'GATA-3', at, gene, transcription, level])]). relacion([sujeto(['Although', 'GATA-3']), verbo([has]), complemento([the, capacity, to, interact, with, the, 'cis-regulatory', 'elements,', it, suppresses, 'IFN-gamma', gene, transcription, via, 'down-regulation', of, 'Stat4'])]). relacion([sujeto(['In', 'humans,', mutations, in, the, 'PAX2', gene]), verbo([cause]), complemento([renal, coloboma, syndrome, that, is, characterized, by, kidney, 'abnormalities,', optic, nerve, colobomas, and, mild, sensorineural, deafness])]). relacion([sujeto(['Cochlear', outgrowth, in, the, mutants, is]), verbo([arrested]), complemento([at, an, early, stage, due, to, apoptosis, of, cells, that, normally, express, 'Pax2', in, the, cochlear, anlage])]). relacion([sujeto(['Because', the, cochlear, phenotypes, observed, in, 'Pax2', mutants, are, more, severe, than, those, observed, in, mice, lacking, 'Otx1', and, 'Otx2,', we, postulate, that, 'Pax2', plays, a, key, role, in]), verbo([regulating]), complemento([the, differential, growth, within, the, cochlear, duct, and, 'thus,', its, proper, outgrowth, and, coiling])]). relacion([sujeto(['Helicobacter', pylori, infection]), verbo([leads]), complemento([to, chronic, gastric, inflammation])]). relacion([sujeto([pylori, at, a, multitude, of, infection, 5]), verbo([stimulated]), complemento([the, expression, of, 'MHC', class, 'II', '(', 4, -, to, 7, -, 'fold),', 'CD80,', and, 'CD86', 'B7', molecules, '(', 10, -, to, 12, -, 'fold)', and, the, 'CD83', costimulatory, molecule, '(', &, 'gt;30-fold)', as, well, as, 'IL-12', secretion, '(', &, 'gt;50-fold)', in, 'DCs,', and, 'thereby,', strongly, induced, their, maturation, and, activation])]). relacion([sujeto(['pylori-pulsed', 'DCs', significantly]), verbo([enhanced]), complemento(['TNF-alpha,', 'IFN-gamma,', and, 'IL-2', secretion, as, well, as, 'T-bet', mRNA, 'levels,', while, 'GATA-3', mRNA, was, lowered])]). relacion([sujeto([pylori, potently]), verbo([induced]), complemento([the, maturation, and, activation, of, human, 'monocyte-derived', 'DC', and, thereby, promote, 'NK', and, 'Th1', effector, responses])]). relacion([sujeto(['Th1-polarized', 'T', cells, were]), verbo([induced]), complemento([especially, by, incubation, with, membrane, preparations, of, 'H'])]). relacion([sujeto(['pylori,']), verbo([suggesting]), complemento([that, membrane, proteins, may, account, for, the, specific, adaptive, immune, response])]). relacion([sujeto(['Here,', we, performed, 'large-scale']), verbo([expressed]), complemento([sequence, tag, analysis, of, leukocytes, isolated, from, the, inshore, hagfish, 'Eptatretus', burgeri])]). relacion([sujeto(['Although', we]), verbo([found]), complemento([many, 'immunity-related', genes, such, as, those, involved, in, lymphocyte, or, hematopoietic, cell, signaling, and, development, as, well, as, cytokine, and, cytokine, receptor, 'genes,', 'MHC', molecules, or, antigen, receptors, were, not, identified])]). relacion([sujeto(['In', 'total,', our, work]), verbo([provides]), complemento([circumstantial, evidence, that, adaptive, immunity, is, unique, to, jawed, vertebrates])]). relacion([sujeto(['Since', 'GATA3', is, prominently]), verbo([expressed]), complemento([in, both, the, inner, ear, and, different, parts, of, the, auditory, nervous, 'system,', it, is, not, clear, whether, the, deafness, in, 'HDR', patients, is, caused, by, peripheral, 'and/or', central, deficits])]). relacion([sujeto(['Therefore,', we]), verbo([have]), complemento([created, and, examined, heterozygous, 'Gata3', knockout, mice])]). relacion([sujeto(['Auditory', brainstem, response, '(', 'ABR)', thresholds, of, alert, heterozygous, 'Gata3', 'mice,', analyzed, from, 1, to, 19, months, of, 'age,', showed, a, hearing]), verbo([loss]), complemento([of, 30, dB, compared, to, 'wild-type', littermates])]). relacion([sujeto(['Neither', physiological, nor, morphological, abnormalities, were]), verbo([found]), complemento([in, the, 'brainstem,', cerebral, 'cortex,', the, outer, or, the, middle, ear])]). relacion([sujeto(['Together,', these, findings, indicate, that, hearing]), verbo([loss]), complemento([following, 'Gata3', haploinsufficiency, is, peripheral, in, origin, and, that, this, defect, is, detectable, from, early, postnatal, development, and, maintains, through, adulthood])]). relacion([sujeto(['Vasoactive', intestinal, peptide, and, its, 'G', 'protein-coupled', 'receptors,', 'VPAC(1)', and, 'VPAC(2),']), verbo([regulate]), complemento([critical, aspects, of, innate, and, adaptive, immunity])]). relacion([sujeto(['T', cell, 'VPAC(2)Rs']), verbo([mediate]), complemento([changes, in, cytokine, 'generation,', which, potently, increase, the, 'Th2/Th1', ratio, and, consequently, shift, the, effector, responses, toward, allergy, and, inflammation])]). relacion([sujeto(['Vasoactive', intestinal, peptide]), verbo([binding]), complemento([to, 'VPAC(2)', on, 'CD4', 'T', cells, specifically, induces, an, 'up-regulation', of, the, 'Th2-type', transcription, factors, 'c-Maf', and, 'JunB,', which, consequently, enhances, 'IL-4', and, 'IL-5', 'production,', leading, to, a, 'Th2-type', phenotype])]). relacion([sujeto(['In', breast, tumours, and, breast, cancer, cell, '(', 'BCC)', 'lines,', microarray, analyses]), verbo([have]), complemento([revealed, that, a, series, of, genes, are, expressed, in, close, association, with, the, oestrogen, 'receptor-alpha', '(', 'ER-alpha)', 'gene,', 'ESR1'])]). relacion([sujeto(['It', exerts, its, biological, effects, through]), verbo([binding]), complemento([to, the, 'IL-12', receptor, '(', 'IL-12R),', a, heterodimer, composed, of, a, 1, and, a, beta2, subunits])]). relacion([sujeto(['The', signaling, beta2, chain, is]), verbo([expressed]), complemento([on, 'Th1', cells, and, to, a, lesser, extent, on, 'Th0', 'cells,', but, not, on, 'Th2', 'cells,', rendering, these, latter, cells, unresponsive, to, 'IL-12'])]). relacion([sujeto(['Polymorphisms', in, the, coding, region, of, the, 'IL-12Rbeta2', gene, were, shown, to, be]), verbo([associated]), complemento([with, atopic, disease])]). relacion([sujeto(['We']), verbo([found]), complemento([five, novel, 'single-nucleotide', polymorphisms, '(', 'SNPs)', in, the, proximal, 1.2, kb, 'IL-12Rbeta2', promoter, 'region,', i])]). relacion([sujeto(['By', functional, comparison, of, both, -, 465, alleles, in, transient, transfection, 'assays,', we, show, that, promoter, activity, is]), verbo([increased]), complemento([in, case, of, the, -, 465, 'G', 'allele,', disrupting, the, intact, 'GATA', site])]). relacion([sujeto(['Comparison', of, the, prevalence, of, -, 465, 'A/G', 'SNP', alleles, in, small, cohorts, of, allergic, asthmatic, and, healthy, control, individuals]), verbo([provided]), complemento([no, evidence, for, an, altered, distribution, in, the, asthmatic, population])]). relacion([sujeto(['In', 'conclusion,', we]), verbo([have]), complemento([identified, a, novel, polymorphic, 'GATA', site, that, may, affect, transciptional, activity, of, the, human, 'IL-12Rbeta2', gene, under, 'GATA3-mediated,', 'Th2-polarizing', conditions])]). relacion([sujeto(['Antigen-presenting', cells, '(', 'APC)', tailor, immune, responses, to, microbial, encounters, by]), verbo([stimulating]), complemento([differentiation, of, 'CD4', 'T', cells, into, the, 'Th1', and, 'Th2', lineages])]). relacion([sujeto(['Strikingly,', of, the, two, 'Notch', ligand, 'families,', 'Delta']), verbo([induces]), complemento(['Th1,', while, 'Jagged', induces, the, alternate, 'Th2', fate])]). relacion([sujeto(['Expression', of, these, different, 'Notch', ligands, on, 'APC', is]), verbo([induced]), complemento([by, 'Th1-', or, 'Th2-promoting', stimuli])]). relacion([sujeto(['Th2', differentiation]), verbo([has]), complemento([been, considered, a, default, process, as, 'APC-derived', instructive, signals, are, unknown])]). relacion([sujeto(['Th2', differentiation]), verbo([induced]), complemento([by, 'APC', is, abrogated, in, 'T', cells, lacking, the, 'Notch', effector, 'RBPJkappa'])]). relacion([sujeto(['Notch', directs, 'Th2', differentiation, by]), verbo([inducing]), complemento(['GATA3', and, by, directly, regulating, il4, gene, transcription, through, 'RBPJkappa', sites, in, a, 3, '\'', enhancer])]). relacion([sujeto(['The', transcriptional, control, of, the, differentiation, of, central, serotonergic, '(', 5, -, 'HT)', neurons, in, vertebrates]), verbo([has]), complemento([recently, come, under, scrutiny, and, has, been, shown, to, involve, the, homeobox, genes, 'Nkx2-2', and, 'Lmx1b,', the, 'Ets-domain', gene, 'Pet1', '(', also, known, as, 'Fev)', and, the, 'zinc-finger', gene, 'Gata3'])]). relacion([sujeto(['Cytokines']), verbo([regulate]), complemento([the, expression, of, key, transcriptional, 'factors,', 'T-bet', and, 'GATA-3,', which, instruct, the, direction, of, 'Th1', and, 'Th2', 'differentiation,', through, changes, in, chromatin, conformation])]). relacion([sujeto(['In', this, 'study,', we, investigated, the, kinetics, of, 'IL-4-mediated', signaling, in, a, transgenic, 'mouse,']), verbo([expressing]), complemento([human, 'IL-4R', on, a, mouse, 'IL-4alphaR-deficient', background])]). relacion([sujeto(['These', 'experiments,', allowing, induction, with, human, 'IL-4', at, defined, 'times,', demonstrated, that, an, 'IL-4', signal, was]), verbo([required]), complemento([at, the, early, stage, of, 'TCR-mediated', 'T', cell, activation, for, lineage, commitment, to, 'Th2,', along, with, structural, changes, in, 'chromatin,', which, take, place, in, the, conserved, noncoding, 'sequence-1', and, -, 2, within, the, 'IL-4', locus])]). relacion([sujeto(['At', later, 'times,', 'however,', 'IL-4', failed, to]), verbo([promote]), complemento([efficient, 'Th2', differentiation, and, decondensation, of, 'chromatin,', even, though, 'GATA-3', was, clearly, induced, in, the, nuclei, by, 'IL-4', stimulation])]). relacion([sujeto(['Moreover,', 'IL-4-mediated', 'Th2', instruction, was, independent, from, cell, division]), verbo([mediated]), complemento([by, initial, 'TCR', stimulation])]). relacion([sujeto(['The', role, of, 'IL-4', signaling, may]), verbo([have]), complemento([a, time, restriction, during, 'Th2', differentiation])]). relacion([sujeto(['In', late, stages, of, initial, 'T', cell, 'activation,', the, chromatin, structure, of, the, 'IL-4', locus]), verbo([retains]), complemento([condensation, state])]). relacion([sujeto(['Homologs', of, rearranging, 'TCR', and, 'Ig', '(', 'B', cell, 'receptor)', genes, are, present, in, jawed, 'vertebrates,', but]), verbo([have]), complemento([not, been, identified, in, other, animal, groups])]). relacion([sujeto(['In', 'contrast,', most, of, the, transcription, factors, that, are, essential, for, the, development, of, mammalian, 'T', and, 'B', lymphocytes, belong, to, multigene, families, that, are, represented, by, members, in, the, majority, of, the, 'metazoans,']), verbo([providing]), complemento([a, potential, bridge, to, prevertebrate, ancestral, roles])]). relacion([sujeto(['This', work, investigates, the, structure, and, regulation, of, homologs, of, specific, transcription, factors, known, to]), verbo([regulate]), complemento([mammalian, 'T', and, 'B', cell, development, in, a, representative, of, the, earliest, diverging, jawed, 'vertebrates,', the, clearnose, skate, '(', 'Raja', 'eglanteria)'])]). relacion([sujeto(['Skate', orthologs, of, mammalian, 'GATA-3,', 'GATA-1,', 'EBF-1,', 'Pax-5,', 'Pax-6,', 'Runx2,', and, 'Runx3']), verbo([have]), complemento([been, characterized])]). relacion([sujeto(['However,', certain, factors, relevant, to, the, 'B', lineage, differ, in, their, 'tissue-specific', expression, patterns, from, their, mouse, 'counterparts,']), verbo([suggesting]), complemento([expanded, or, divergent, 'B', lineage, characteristics, or, tissue, specificity, in, these, animals])]). relacion([sujeto(['However,', definitive, genetic, evidence, for, these, roles]), verbo([has]), complemento([been, lacking])]). relacion([sujeto(['Here,', we, show, that, 'Cre-mediated', mutation, of, the, gene, encoding, 'BMP', receptor, 1, 'A', in, the, surface, epithelium, and, its, derivatives]), verbo([causes]), complemento([arrest, of, tooth, morphogenesis, and, lack, of, external, hair])]). relacion([sujeto(['Lef1', expression, is, 'maintained,', but]), verbo([nuclear]), complemento(['beta-catenin', is, absent, from, the, epithelium, of, severely, affected, mutant, 'follicles,', indicating, that, activation, of, the, 'WNT', pathway, lies, downstream, of, 'BMPR1A', signaling, in, postnatal, follicles])]). relacion([sujeto(['These', results]), verbo([provide]), complemento([definitive, genetic, evidence, that, epithelial, 'Bmpr1a', is, required, for, completion, of, tooth, 'morphogenesis,', and, regulates, terminal, differentiation, and, proliferation, in, postnatal, hair, follicles])]). relacion([sujeto(['This', system, allowed, us, to, investigate, the, effect, of]), verbo([loss]), complemento([of, 'GATA3', expression, in, in, vitro, differentiated, 'Th2', cells])]). relacion([sujeto(['After', ablation, of, 'GATA3,', we, detected, reduced, production, of, all, 'Th2', 'cytokines,']), verbo([increased]), complemento(['DNA', methylation, at, the, 'IL-4', gene, 'locus,', and, decreased, histone, hyperacetylation, at, the, 'IL-5', gene, locus, but, not, significantly, so, at, the, 'IL-13/IL-4', gene, loci])]). relacion([sujeto(['We']), verbo([report]), complemento([a, novel, approach, to, gene, expression, profiling, using, the, 'Nottingham', 'Prognostic', 'Index', '(', 'NPI)', to, stratify, 26, patients, with, invasive, breast, carcinoma])]). relacion([sujeto(['As', an, aggregate, index, of, parameters, reflecting, metastatic, 'potential,', growth, 'rate,', and, genetic, instability, the, 'NPI']), verbo([has]), complemento([distinct, advantages, over, other, clinicopathologic, features, used, to, segregate, breast, cancer, patients])]). relacion([sujeto(['Using', 'RNA', extracted, from, 26, tumors, and, cDNA, microarrays, with, 23, 343, unique, genetic, 'elements,', 84, genes, and]), verbo([expressed]), complemento([sequence, tags, were, identified, whose, expression, patterns, correlated, with, 'NPI'])]). relacion([sujeto(['Among', the, 84, genetic, elements, were, seven, previously, implicated, in, neoplastic, progression, '(', including, the, two, demonstrating, differential, expression, by, 'IHC),', 11, without, specific, cancer, association, but, localized, to, chromosomal, sites, whose]), verbo([loss]), complemento([or, gain, has, been, identified, in, cytogenetic, studies, of, breast, 'carcinoma,', and, 73, not, previously, associated, with, breast, carcinoma])]). relacion([sujeto(['Collectively,', the, expression, patterns, of, these, 84, elements]), verbo([have]), complemento([potential, to, distinguish, high, and, low, 'NPI', patient, samples])]). relacion([sujeto(['In', this, study, we, show, that]), verbo([activated]), complemento(['CD4(+)', 'T', cells, from, 'c-FLIP(L)-transgenic', mice, produce, increased, amounts, of, 'Th2', cytokines, and, decreased, amounts, of, 'Th1', cytokines])]). relacion([sujeto(['This', correlates, with]), verbo([increased]), complemento([serum, concentrations, of, the, 'Th2-dependent', 'IgG1', and, 'IgE'])]). relacion([sujeto(['The', 'Th2', bias, of, 'c-FLIP(L)-transgenic', 'CD4(+)', 'T', cells, parallels, impaired, 'NF-kappa', 'B', activity, and]), verbo([increased]), complemento([levels, of, 'GATA-3,', which, 'contribute,', 'respectively,', to, decreased, 'IFN-gamma', and, increased, 'Th2', cytokines])]). relacion([sujeto(['The', 'Th2', bias, of, 'c-FLIP(L)-transgenic', mice, extends, to, an]), verbo([enhanced]), complemento([sensitivity, to, 'OVA-induced', asthma])]). relacion([sujeto(['Taken', 'together,', these, results, show, that, 'c-FLIP(L)', can, influence, cytokine, gene, expression, to]), verbo([promote]), complemento(['Th2-driven', allergic, 'reaction,', in, addition, to, its, traditional, role, of, blocking, caspase, activation, induced, by, death, receptors])]). relacion([sujeto(['Differentiation', of, naive, 'CD4', 'T', cells, into, 'type-2', helper, '(', 'Th2)', cells, is, accompanied, by, chromatin, remodeling, including, hyperacetylation, of, histones, 'H3', and, 'H4', in, the, nucleosomes]), verbo([associated]), complemento([with, the, 'IL-4,', 'IL-13,', and, 'IL-5', genes])]). relacion([sujeto(['Histone', hyperacetylation, of, the, 'IL-5', gene, displayed, a, delayed, kinetics, compared, with, that, of, the, 'IL-4', and, 'IL-13', 'genes,']), verbo([suggesting]), complemento([a, distinct, remodeling, mechanism, for, the, 'IL-5-gene', locus])]). relacion([sujeto(['CD28-costimulation', selectively]), verbo([enhanced]), complemento([histone, hyperacetylation, of, the, 'IL-5', gene, locus, that, appeared, to, be, mediated, through, 'NF-kappaB', activation, and, subsequent, 'up-regulation', of, 'GATA3'])]). relacion([sujeto(['Recently', many, intracellular, molecules]), verbo([have]), complemento([been, reported, to, regulate, cytokine, expression, and, 'T', cell, differentiation])]). relacion([sujeto(['GATA-3', and, 'T-box']), verbo([expressed]), complemento([in, 'T', cells, '(', 'T-bet)', are, transcription, factors, that, play, a, critical, role, in, the, development, of, 'Th2', and, 'Th1', 'immunity,', respectively])]). relacion([sujeto(['Suppressor', of, cytokine, signalling, '(', 'SOCS)-3', and, 'SOCS-5,', are, negative, regulators, of, the, cytokine, signalling]), verbo([induced]), complemento([by, 'IL-12', and, 'IL-4,', respectively])]). relacion([sujeto(['Txk', is, a, transcription, factor, that]), verbo([activates]), complemento(['IFN-gamma', gene, directly])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento(['GATA-3', and, 'Txk', might, be, involved, in, skin, 'lesions,', while, 'SOCS-3', might, be, associated, with, an, imbalance, of, cytokines, that, is, difficult, to, normalize, in, atopic, dermatitis])]). relacion([sujeto(['Differentiation', of, naïve, 'CD4', 'T', cells, into, 'T', helper, '(', 'Th)', 2, cells]), verbo([requires]), complemento([signaling, through, the, 'T', cell, receptor, and, an, appropriate, cytokine, environment])]). relacion([sujeto(['In', vivo, 'IL-2', neutralization]), verbo([inhibits]), complemento(['IL-4', production, in, two, models])]). relacion([sujeto(['Studies', of, restriction, enzyme, accessibility, and]), verbo([binding]), complemento([of, 'Stat5', to, chromatin, indicate, that, 'IL-2', mediates, its, effect, by, stabilizing, the, accessibility, of, the, 'Il4', gene])]). relacion([sujeto(['The', cell, 'line,', 'US/VOT-33,']), verbo([expressed]), complemento(['GATA3,', the, bHLH, transcription, factor, 'NeuroD', and, the, 'POU-domain', transcription, factor, 'Brn3a,', as, do, auditory, neuroblasts, in, vivo])]). relacion([sujeto(['Auditory', and, vestibular, neurons, form, from, neuroblasts, that]), verbo([express]), complemento(['NeuroD', and, that, migrate, from, the, 'antero-ventral,', otic, epithelium, at, 'E9'])]). relacion([sujeto(['On', the, medial, 'side,', neuroblasts, and, epithelial, cells]), verbo([express]), complemento(['GATA3', but, on, the, lateral, side, they, do, not])]). relacion([sujeto([5, most, auditory, neurons]), verbo([express]), complemento(['GATA3', but, no, longer, express, 'NeuroD,', whereas, vestibular, neurons, express, 'NeuroD', but, not, 'GATA3'])]). relacion([sujeto(['Neuroblasts']), verbo([expressing]), complemento(['NeuroD', and, 'GATA3', were, located, in, the, 'ventral,', otic, 'epithelium,', the, adjacent, mesenchyme, and, the, developing, auditory, ganglion])]). relacion([sujeto(['The', results]), verbo([suggest]), complemento([that, auditory, and, vestibular, neurons, arise, from, 'different,', otic, epithelial, domains, and, that, they, gain, their, identity, prior, to, migration])]). relacion([sujeto(['The', 'hypoparathyroidism,', 'deafness,', and, renal, dysplasia, '(', 'HDR)', syndrome, is, an, autosomal, dominant, disorder]), verbo([caused]), complemento([by, mutations, of, the, dual, zinc, finger, transcription, 'factor,', 'GATA3'])]). relacion([sujeto(['The', 'C-terminal', zinc, finger, '(', 'ZnF2)']), verbo([binds]), complemento(['DNA,', whereas, the, 'N-terminal', finger, '(', 'ZnF1)', stabilizes, this, 'DNA', binding, and, interacts, with, other, zinc, finger, 'proteins,', such, as, the, 'Friends', of, 'GATA', '(', 'FOG)'])]). relacion([sujeto(['We']), verbo([have]), complemento([investigated, seven, 'HDR', probands, and, their, families, for, 'GATA3', abnormalities, and, have, identified, two, nonsense, mutations, '(', 'Glu-228', -, -, &, 'gt;', 'Stop', and, 'Arg-367', -, -, &, 'gt;', 'Stop);', two, intragenic, deletions, that, result, in, frameshifts, from, codons, 201, and, 355, with, premature, terminations, at, codons, 205, and, 370, ',', 'respectively;', one, acceptor, splice, site, mutation, that, leads, to, a, frameshift, from, codon, 351, and, a, premature, termination, at, codon, 367, ;, and, two, missense, mutations, '(', 'Cys-318', -, -, &, 'gt;', 'Arg', and, 'Asn-320', -, -, &, 'gt;', 'Lys)'])]). relacion([sujeto(['The', functional, effects, of, these, 'mutations,', together, with, a, previously]), verbo([reported]), complemento(['GATA3', 'ZnF1', mutation, and, seven, other, engineered, 'ZnF1', 'mutations,', were, assessed, by, electrophoretic, mobility, 'shift,', 'dissociation,', yeast, 'two-hybrid', and, glutathione, 'S-transferase', 'pull-down', assays])]). relacion([sujeto(['Mutations']), verbo([involving]), complemento(['GATA3', 'ZnF2', or, adjacent, basic, amino, acids, resulted, in, a, loss, of, 'DNA', 'binding,', but, those, of, 'ZnF1', either, lead, to, a, loss, of, interaction, with, specific, 'FOG2', 'ZnFs', or, altered, 'DNA-binding', affinity])]). relacion([sujeto(['These', findings, are, consistent, with, the, proposed, 'three-dimensional', model, of, 'ZnF1,', which]), verbo([has]), complemento([separate, 'DNA', and, protein, binding, surfaces])]). relacion([sujeto(['Thus,', our, 'results,', which, expand, the, spectrum, of, 'HDR-associated', 'GATA3', mutations, and]), verbo([report]), complemento([the, first, acceptor, splice, site, 'mutation,', help, to, elucidate, the, molecular, mechanisms, that, alter, the, function, of, this, zinc, finger, transcription, factor, and, its, role, in, causing, this, developmental, anomaly])]). relacion([sujeto(['We', show, here, that, 'IL-4', affects, 'Th1', cell, responses, by, two, developmentally]), verbo([regulated]), complemento([mechanisms])]). relacion([sujeto(['During', the, commitment, phase, of, naive, 'CD4+', 'T', 'cells,', 'IL-4']), verbo([inhibits]), complemento(['Th1', cell, differentiation, and, induces, a, reversion, of, developing, 'Th1', cells, to, the, 'Th2', lineage])]). relacion([sujeto(['IL-4', secreting, and, nonsecreting, cells, from, 'Th2', cultures]), verbo([have]), complemento([a, similar, probability, of, producing, 'IL-4', upon, subsequent, 'stimulation,', implying, that, there, is, stochastic, element, in, 'IL-4', production, by, stimulated, 'Th2', cells])]). relacion([sujeto(['Purified', 'IL-4', producers, and, nonproducers]), verbo([have]), complemento([similar, 'Gata3', and, 'c-maf', mRNA, expression])]). relacion([sujeto(['However,', upon, 'TCR', 'stimulation,', site, 'VA,', which, is, 5, kB, 3, '\'', of, exon, 4, ',', displayed, a, striking]), verbo([increase]), complemento([in, accessibility, but, 'REA', was, 2, -, to, 3, -, fold, greater, in, producers, than, nonproducers])]). relacion([sujeto(['Cyclosporin', 'A', treatment]), verbo([inhibited]), complemento(['VA', 'opening,', implying, the, involvement, of, 'NFAT', in, increased, 'VA', accessibility])]). relacion([sujeto(['Induction', of, 'VA', accessibility, is, sensitive, to, 'cycloheximide,']), verbo([suggesting]), complemento([an, additional, 'factor(s)', is, needed])]). relacion([sujeto(['Thus,', opening, of, 'VA', is, a, probabilistic, event, determining, which, 'Th2', cells]), verbo([transcribe]), complemento(['Il4'])]). relacion([sujeto(['Here,', we, identify, a, 'Sonic', hedgehog, '(', 'Shh)-regulated', cascade, of, transcription, factors, that]), verbo([acts]), complemento([to, generate, a, specific, subset, of, 5, -, 'HT', neurons])]). relacion([sujeto([1, cooperate, to]), verbo([induce]), complemento([the, closely, related, 'zinc-finger', transcription, factors, 'Gata2', and, 'Gata3'])]). relacion([sujeto(['Gata2', in, turn, is, necessary, and, sufficient, to]), verbo([activate]), complemento([the, transcription, factors, 'Lmx1b', and, 'Pet1,', and, to, induce, 5, -, 'HT', neurons, within, r1])]). relacion([sujeto(['In', contrast, to, 'Gata2,', 'Gata3', is, not]), verbo([required]), complemento([for, the, specification, of, rostral, 5, -, 'HT', neurons, and, appears, unable, to, substitute, for, the, loss, of, 'Gata2'])]). relacion([sujeto(['Our', findings]), verbo([reveal]), complemento([that, the, identity, of, closely, related, 5, -, 'HT', subclasses, occurs, through, distinct, responses, of, adjacent, rostrocaudal, progenitor, domains, to, broad, ventral, inducers])]). relacion([sujeto(['Expansion', of, adipose, tissue, mass, results, from]), verbo([increased]), complemento([number, and, size, of, adipocyte, cells])]). relacion([sujeto(['We', hypothesized, that, subcutaneous, abdominal, preadipocytes, in, obese, individuals, might]), verbo([have]), complemento([an, intrinsically, higher, propensity, to, differentiate, into, adipocytes])]). relacion([sujeto(['The', lower, differentiation, potential, of, preadipocytes, in, the, obese, subjects, might, be, 'due,', at, least, 'partly,', to]), verbo([decreased]), complemento([glucocorticoid, receptor, expression])]). relacion([sujeto(['T', helper, type, 2, '(', 'Th2)', cells, secrete, 'IL-4,', 'IL-5,', 'IL-10,', and, 'IL-13', and]), verbo([mediate]), complemento([allergic, and, asthmatic, disease])]). relacion([sujeto(['Because', 'GATA-3', is, also, crucial, for, development, of, the, 'T', lineage, and, throughout, thymic, 'development,', direct, demonstration, that, 'GATA-3', is]), verbo([required]), complemento([for, 'Th2', development, by, targeted, deletion, has, been, lacking])]). relacion([sujeto(['Using', a, conditional, knockout, 'approach,', we]), verbo([found]), complemento([that, 'GATA-3', is, required, for, optimal, 'Th2', cytokine, production, in, vitro, and, in, vivo])]). relacion([sujeto(['Our', data, also, show, that, 'GATA-3', expression, must, be, sustained, to]), verbo([maintain]), complemento([the, 'Th2', phenotype])]). relacion([sujeto(['The', objective, of, this, study, was, to, determine, whether, and, how, 'MSSM-002']), verbo([modulates]), complemento([an, established, 'T(H)2', response, and, whether, the, actions, of, 'MSSM-002', on, 'T(H)2', cell, differs, from, corticosteroids])]). relacion([sujeto(['Apoptosis', and, 'T(H)2', transcription, factor, 'GATA-3', expression, and]), verbo([binding]), complemento([to, 'IL-4', gene, promoter, and, 'V(A)', enhancer, in, 'MSSM-002-treated', 'D10', cells, were, also, determined])]). relacion([sujeto(['MSSM-002', significantly]), verbo([decreased]), complemento(['antigen-induced', proliferation, and, 'IL-4', and, 'IL-5', production, but, increased, 'IFN-gamma', production, by, 'T(H)2-SPCs,', whereas, dexamethasone, suppressed, 'IFN-gamma', as, well, as, 'IL-4', and, 'IL-5'])]). relacion([sujeto(['MSSM-002', also]), verbo([suppressed]), complemento(['T(H)2', cytokine, secretion, by, 'D10', 'cells,', and, in, contrast, to, 'dexamethasone,', 'MSSM-002', did, not, induce, apoptosis, of, 'D10', cells])]). relacion([sujeto(['MSSM-002', markedly]), verbo([suppressed]), complemento(['GATA-3', mRNA, and, protein, expression, and, the, binding, to, 'IL-4', gene, promoter, and, 'V(A)', enhancer, in, 'D10', cells])]). relacion([sujeto(['CD4', 'T', cells, from, 'GATA-3+/-', individuals]), verbo([expressed]), complemento([significantly, reduced, levels, of, 'GATA-3,', associated, with, markedly, decreased, 'T', helper, cell, '(', 'Th)2', frequencies, in, vivo, and, in, vitro])]). relacion([sujeto(['Moreover,', 'GATA-3', mRNA, levels]), verbo([increased]), complemento([under, 'Th2-inducing', conditions, and, decreased, under, 'Th1-inducing', conditions])]). relacion([sujeto(['Taken', 'together,', the, data, strongly]), verbo([suggest]), complemento([that, 'GATA-3', is, an, important, transcription, factor, in, regulating, human, 'Th2', cell, differentiation, in, vivo])]). relacion([sujeto(['We']), verbo([have]), complemento([reported, that, injection, of, marijuana, 'cannabinoids,', such, as, 'Delta(9)-tetrahydrocannabinol', '(', 'THC),', into, 'mice,', followed, by, infection, with, 'Legionella', pneumophila, '(', 'Lp),', suppresses, the, development, of, 'cell-mediated', immunity, 'T', helper, 1, '(', 'Th1)', activity])]). relacion([sujeto(['These', effects, are, accompanied, by, suppression, of, interleukin, '(', 'IL)-12', and, interferon, '(', 'IFN)', gamma, production, and, enhancement, of, 'IL-4', production]), verbo([suggesting]), complemento(['THC-induced', 'T', helper, cell, biasing])]). relacion([sujeto(['The', results, showed, that, 'THC']), verbo([suppressed]), complemento(['IL-12Rbeta2', but, increased, 'GATA3'])]). relacion([sujeto(['It', was, determined, that, 'SR1', attenuated, the, 'THC', suppression, of, 'IL-12Rbeta2,', while, 'SR2', attenuated, the]), verbo([increase]), complemento([in, 'GATA3', mRNA])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, 'THC', suppresses, 'Th1', biasing, activity, such, as, 'IL-12Rbeta2', by, a, 'CB1', mediated, mechanism, and, enhances, the, 'Th2', biasing, 'activity,', 'GATA3,', by, a, 'CB2', mechanism])]). relacion([sujeto(['Chronic', morphine, treatment, in, animal, models]), verbo([has]), complemento([been, shown, to, alter, a, number, of, immune, parameters, including, suppression, of, cellular, immunity])]). relacion([sujeto(['We', had, previously, shown, that, chronic, morphine, treatment, in, vivo, and, in, vitro]), verbo([decreases]), complemento(['IL-2', and, 'IFNgamma', '(', 'Th1)', protein, levels, and, increases, 'IL-4', and, 'IL-5', '(', 'Th2)', protein, levels, in, a, 'time-dependent', manner])]). relacion([sujeto(['In', addition, in, this, 'paper,', we, show, that, chronic, morphine, treatment, resulted, in, a]), verbo([decrease]), complemento([in, 'IFNgamma', and, 'IL-2', mRNA, and, an, increase, in, 'IL-4', and, 'IL-5', mRNA, accumulation, in, murine, splenocytes])]). relacion([sujeto(['Furthermore,', chronic, morphine, treatment]), verbo([inhibited]), complemento(['IFNgamma', promoter, activity, and, increased, 'IL-4', promoter, activity, in, respective, promoter, transfected, primary, 'T', cells])]). relacion([sujeto(['In', 'addition,', we, also, demonstrate, that, chronic, morphine, treatment, resulted, in, an]), verbo([increase]), complemento([in, 'GATA', 3, binding, to, 'DNA', consensus, elements, in, electromobility, shift, assays, and, an, increase, in, 'GATA', 3, protein, and, mRNA, levels])]). relacion([sujeto(['In', 'contrast,', chronic, morphine, treatment, resulted, in, a]), verbo([decrease]), complemento([in, 'T-bet', mRNA, levels])]). relacion([sujeto(['From', these, 'data,', we, conclude, that, chronic, morphine, treatment, differentiates, 'T', helper, cell, to, 'Th2', effector, cells, by]), verbo([modulating]), complemento([key, master, switches, that, results, in, committing, 'T', helper, cell, to, a, 'Th2', phenotype])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, neonatal, and, adult, thymic, 'CD4', 'SP', 'T', cells, in, the, final, stage, of, maturation, are, relatively, immature, compared, with, adult, splenic, 'CD4', 'SP', 'T', cells])]). relacion([sujeto(['The', cytokine, production, profile, of, neonatal, thymic, 'CD4', 'SP', 'T', cells]), verbo([suggests]), complemento([that, they, are, inclined, towards, a, 'T(h)2', response])]). relacion([sujeto(['PU1', and, 'RelB', are, two, transcription, factors]), verbo([involved]), complemento([in, the, development, of, murine, myeloid, 'DC', '(', 'MDC)'])]). relacion([sujeto(['Three', 'DC', populations, were]), verbo([found]), complemento([in, the, thymus])]). relacion([sujeto([1, ')', 'CD123(-/lo)HLA-DR(hi)', 'DC']), verbo([expressing]), complemento(['PU1', and, 'RelB;', 2, ')', 'CD123(hi)HLA-DR(+)', 'DC', expressing, only, 'pre-Talpha,', the, expression, of, which, was, similar, to, that, of, 'MDC', and, 'PDC', from, peripheral, 'blood;', and, 3, ')', a, new, mature, 'CD123(hi)HLA-DR(hi)', 'PDC', population, with, 'pre-Talpha,', 'PU1', and, 'RelB', mRNAs])]). relacion([sujeto(['In', 'culture,', most, 'CD34(+)CD1a(-)', progenitors, remained, 'CD1a(-)CD123(-);', had, a, 'T', and, natural, killer, cell, differentiation, 'potential;', and]), verbo([expressed]), complemento(['Gata-3', mRNA, contrary, to, 'DC', precursors])]). relacion([sujeto(['A', few, cells, '(', 10, '%', ')', became, 'CD1a(+)CD123(+)']), verbo([expressing]), complemento(['pre-Talpha,', 'PU1,', and, 'RelB', mRNAs, and, were, able, to, differentiate, into, typical, 'Langerhans', cells, with, transforming, growth, 'factor-beta'])]). relacion([sujeto(['Coculture', of, thymic, progenitors, on, a, murine, cell, line, generated, 'CD123(hi)CD1a(-)', cells, with, typical, 'PDC', 'morphology,']), verbo([expressing]), complemento(['pre-Talpha', but, not, 'PU1', and, 'RelB', transcripts])]). relacion([sujeto(['Lovastatin']), verbo([induced]), complemento([the, expression, of, 'GATA3', and, the, phosphorylation, of, 'STAT6,', whereas, it, inhibited, tyrosine, phosphorylation, of, 'Janus', kinase, 2, ',', tyrosine, kinase, 2, ',', and, 'STAT4'])]). relacion([sujeto(['Inhibition', of, the, 'Janus', 'kinase-STAT4', pathway, by, lovastatin]), verbo([modulated]), complemento(['T0', to, 'Th1', differentiation, and, reduced, cytokine, '(', 'IFN-gamma', and, 'TNF-alpha)', 'production,', thus, inducing, 'Th2', cytokines, '(', 'IL-4,', 'IL-5,', and, 'IL-10)'])]). relacion([sujeto(['It']), verbo([inhibited]), complemento(['T-bet', '(', 'T', box, transcription, 'factor)', and, 'NF-kappaB', in, activated, 'T', cells, and, significantly, reduced, infiltration, of, 'CD4-', and, 'MHC', class, 'II-positive', cells, to, 'CNS'])]). relacion([sujeto(['Further,', it, stabilized, 'IL-4', production, and, 'GATA-3', expression, in, differentiated, 'Th2', 'cells,', whereas, in, differentiated, 'Th1', cells, it]), verbo([inhibited]), complemento([the, expression, of, 'T-bet', and, reduced, the, production, of, 'IFN-gamma'])]). relacion([sujeto(['Moreover,', 'lovastatin-exposed', macrophage, and, 'BV2', '(', 'microglia)', in, allogeneic, 'MLRs']), verbo([induced]), complemento([the, production, of, the, 'anti-inflammatory', cytokine, 'IL-10'])]). relacion([sujeto(['These', observations, indicate, that, the, 'anti-inflammatory', effects, of, lovastatin, are]), verbo([mediated]), complemento([via, 'T', cells, as, well, as, 'APCs,', because, it, modulates, the, polarization, patterns, of, naive, 'T', cell, activation, in, an, 'APC-independent', system])]). relacion([sujeto(['Together,', these, findings]), verbo([reveal]), complemento([that, lovastatin, may, have, possible, therapeutic, value, involving, new, targets, '(', in, both, 'APCs', and, 'T', 'cells)', for, the, treatment, of, multiple, sclerosis, and, other, inflammatory, diseases])]). relacion([sujeto(['Two', 'isoforms,', 'GATA-2', and, 'GATA-3,', are, specifically]), verbo([expressed]), complemento([in, murine, preadipocytes, but, not, mature, adipocytes])]). relacion([sujeto(['Continuous', expression, of, 'GATA', factors, in, preadipocyte, cell, lines]), verbo([inhibits]), complemento([terminal, differentiation, into, mature, adipocytes])]). relacion([sujeto(['The', inhibitory, effect, of, 'GATA', on, adipogenesis, is]), verbo([mediated]), complemento([in, part, by, suppression, of, promoters, of, adipogenic, 'factors,', including, peroxisome, 'proliferator-activated', receptor, 'gamma,', but, additional, mechanisms, are, also, likely, to, be, in, effect])]). relacion([sujeto(['Whether', 'GATA', factors, are, also]), verbo([involved]), complemento([in, the, commitment, of, multipotent, mesenchymal, stem, cells, to, progenitors, of, the, adipogenic, lineage, is, under, investigation])]). relacion([sujeto(['Injection', of, truncated, 'c-met', mRNA, resulted, in, a, marked]), verbo([decrease]), complemento([in, the, number, of, circulating, blood, cells])]). relacion([sujeto(['Overall,', the, present, study, demonstrated, that, 'HGF', is, necessary, for, primitive, hematopoiesis, by]), verbo([regulating]), complemento([the, expression, of, 'SCL'])]). relacion([sujeto(['However,', 'NF-ATc2-deficient', 'Th', cells, display, hyperproliferation, in, response, to, 'stimulation,']), verbo([suggesting]), complemento([that, 'NF-ATc2', functions, as, a, negative, regulator, of, 'Th', cell, 'activation/proliferation'])]). relacion([sujeto(['In', this, study, we, show, that, the, transcriptional, repressor, of, 'GATA', '(', 'ROG)', is, a, direct]), verbo([target]), complemento([gene, of, 'NF-ATc2', and, that, 'NF-ATc2-deficient', 'Th', cells, are, unable, to, fully, 'up-regulate', 'ROG', upon, stimulation])]). relacion([sujeto(['The', transcription, factor, 'GATA-3']), verbo([has]), complemento([been, shown, to, play, an, important, role, for, the, in, vitro, induction, of, 'T(h)2', cells])]). relacion([sujeto(['After', immunization, with, 'OVA,', the, 'double-transgenic', mice, showed]), verbo([increased]), complemento([expression, of, 'GATA-3', in, 'antigen-reactive', fresh, 'CD4(+)', 'T', 'cells,', and, higher, production, of, 'IL-5', and, 'IL-13', in, cultured, spleen, cells, in, the, presence, of, cognate, antigen, without, any, polarizing, conditions, for, 'T(h)2', cells])]). relacion([sujeto(['Moreover,', the, immunized, 'double-transgenic', mice, showed, a, higher]), verbo([increase]), complemento([of, in, vivo, secretion, of, 'IL-5', and, 'IL-13', in, bronchoalveolar, lavage, fluid, after, 'OVA', aerosol, challenging])]). relacion([sujeto(['These', findings]), verbo([provide]), complemento([direct, evidence, that, 'antigen-stimulated', 'CD4(+)', 'T', cells, in, the, immunized, mice, have, already, been, committed, into, 'T(h)2', cells, producing, 'IL-5', and, 'IL-13', selectively, through, enhanced, 'GATA-3', expression, in, 'vivo,', thereby, inducing, higher, production, of, 'antigen-specific', antibody, for, three, isotypes, other, than, 'IgM'])]). relacion([sujeto(['In', comparison, with, the, normal, liver, tissues, from, the, healthy, 'donors,', it, was]), verbo([found]), complemento([that, while, remained, unmethylated, the, 'ABL,', 'CAV,', 'EPO,', 'GATA3,', 'LKB1,', 'NEP,', 'NFL,', 'NIS', and, p27KIP1, 'genes,', varying, extents, of, the, 'HCC', specific, hypermethylation, were, found, associated, with, the, 'ABO,', 'AR,', 'CSPG2,', cyclin, 'a1,', 'DBCCR1,', 'GALR2,', 'IRF7,', 'MGMT,', 'MT1A,', 'MYOD1,', 'OCT6,', 'p57KIP2,', 'p73,', 'WT1', 'genes,', and, demethylation, with, the, 'MAGEA1', 'gene,', respectively])]). relacion([sujeto(['The', concordant, methylation, behaviors, of, nineteen, 'genes,', including, the, four, previously, studied, and, their, association, with, cirrhosis]), verbo([has]), complemento([been, evaluated, by, the, best, subgroup, selection, method])]). relacion([sujeto(['The', data, presented, in, this]), verbo([report]), complemento([would, enable, us, to, shape, our, understanding, of, the, mechanisms, for, the, 'HCC', specific, loss, of, the, epigenetic, stability, of, the, 'genome,', as, well, as, the, strategy, of, developing, the, novel, robust, methylation, based, diagnostic, and, prognostic, tools])]). relacion([sujeto(['The', transcription, factor, 'GATA-3', is]), verbo([expressed]), complemento([at, every, stage, of, thymic, 'development,', but, its, role, in, thymocyte, differentiation, is, unknown])]). relacion([sujeto(['The', fact, that, 'RAG', chimeric, animals, lacking, 'GATA-3', cannot, generate, early, thymocytes, from, common, lymphoid, progenitors]), verbo([has]), complemento([thus, far, precluded, investigation, of, the, function, of, 'GATA-3', in, the, thymus])]). relacion([sujeto(['Our', studies, revealed, that, 'GATA-3', is]), verbo([involved]), complemento([in, beta, selection, and, is, indispensable, for, 'single-positive', 'CD4', thymocyte, development])]). relacion([sujeto(['Thus,', our, data, demonstrate, that, the, coordinated, and]), verbo([regulated]), complemento([expression, of, 'GATA-3', at, each, stage, of, thymic, development, is, critical, for, the, generation, of, mature, 'T', cells])]). relacion([sujeto(['IL-27,', a, novel, heterodimeric, cytokine, produced, by, 'antigen-presenting', 'cells,', signals, through, the, 'T', cell, cytokine, receptor, '(', 'TCCR)/WSX-1']), verbo([expressed]), complemento([on, naïve, 'CD4+', 'T', cells, and, natural, killer, cells])]). relacion([sujeto(['We']), verbo([report]), complemento([here, that, 'IL-27', stimulation, in, developing, murine, 'T', helper, cells, potently, induces, the, expression, of, the, major, 'TH1-specific', transcription, factor, 'T-bet', and, its, downstream, target, 'IL-12R', 'beta2,', independently, of, 'IFN', gamma])]). relacion([sujeto(['In', 'addition,', 'IL-27']), verbo([suppresses]), complemento([basal, expression, of, 'GATA-3,', the, critical, 'TH2-specific', transcription, factor, that, inhibits, 'TH1', development, by, 'down-regulating', signal, transducer, and, activator, of, transcription, '(', 'Stat)', 4])]). relacion([sujeto(['IL-27', signaling, through, 'TCCR/WSX-1']), verbo([induces]), complemento([phosphorylation, of, 'Stat1,', 'Stat3,', 'Stat4,', and, 'Stat5'])]). relacion([sujeto(['Stat1', is]), verbo([required]), complemento([for, suppression, of, 'GATA-3,', but, 'T-bet', induction, by, 'IL-27', can, also, be, mediated, through, a, 'Stat1-independent', pathway])]). relacion([sujeto(['Similarly,', 'IL-27']), verbo([induces]), complemento(['T-bet', expression, in, primary, natural, killer, 'cells,', but, this, does, not, result, in, an, increase, of, 'IFN', gamma, production, or, cytotoxic, activity])]). relacion([sujeto(['To', investigate, the, changes, of, the, 'GATA-3', expression, and, development, of, anterior, chamber]), verbo([associated]), complemento([immune, deviation, '(', 'ACAID)', after, anterior, chamber, '(', 'AC)', injection, of, interphotoreceptor, retinoid, binding, protein, '(', 'IRBP)', under, ocular, inflammation])]). relacion([sujeto(['ACAID', was]), verbo([induced]), complemento([by, injection, of, 'IRBP', into, the, 'AC', of, 30, 'Spar-Dawley', '(', 'SD)', rats])]). relacion([sujeto(['In', 7, days, 'group,', the, serum, 'IL-4', and, 'GATA-3', expression, in, spleen]), verbo([increased]), complemento([8, days, after, 'IRBP', inoculation])]). relacion([sujeto(['In', ocular, 'inflammation,', the, 'up-regulation', of, 'GATA-3', expression, is]), verbo([inhibited]), complemento([and, 'ACAID', development, is, blocked, after, antigen, was, injected, into, anterior, chamber])]). relacion([sujeto(['IL-4,']), verbo([acting]), complemento([through, 'Stat6,', plays, a, major, role, in, 'Th2', 'differentiation;', 'IL-2', has, also, been, reported, to, be, essential])]). relacion([sujeto(['Here,', we]), verbo([report]), complemento([that, retroviral, '(', 'RV)-mediated', expression, of, a, constitutively, active, 'Stat5A', mutant, '(', 'STAT5A1*6)', can, fully, restore, 'IL-4', production, when, naive, 'CD4', 'T', cells, are, primed, in, the, absence, of, 'IL-2'])]). relacion([sujeto(['Furthermore,', 'STAT5A1*6', expression]), verbo([causes]), complemento(['Th2', differentiation, in, the, absence, of, 'IL-4', or, in, 'Stat6-', or, 'IL-4Ralpha-deficient', cells])]). relacion([sujeto(['Infection', with, 'STAT5A1*6-NGFR-RV', does, not]), verbo([enhance]), complemento(['GATA-3', expression])]). relacion([sujeto(['Stat5A']), verbo([binds]), complemento([to, 'HSII', and, 'HSIII', sites, of, the, 'Il4', gene])]). relacion([sujeto(['The', 'GATA-3', transcription, factor]), verbo([has]), complemento([a, determinant, role, in, 'T', cell, specification, and, is, an, essential, mediator, of, 'T', helper, 2, -, type, polarized, immune, responses])]). relacion([sujeto(['While', both, committed, 'NK', precursors, and, mature, 'NK', cells]), verbo([express]), complemento(['GATA-3,', a, role, of, this, transcription, factor, in, murine, 'NK', cell, differentiation, is, not, known])]). relacion([sujeto(['We']), verbo([found]), complemento([that, 'NK', 'cells,', in, contrast, to, 'T', 'cells,', can, be, generated, in, the, absence, of, 'GATA-3'])]). relacion([sujeto(['However,', while, 'GATA-3', antagonizes, 'IFN-gamma', production, in, differentiating, 'T', 'cells,', 'GATA-3-deficient', 'NK', cells, paradoxically, produced, less, 'IFN-gamma', compared, to, control, 'NK', cells, and, failed, to]), verbo([provide]), complemento([early, protection, in, vivo, against, infection, with, 'Listeria', monocytogenes])]). relacion([sujeto(['Our', results]), verbo([suggest]), complemento([that, 'GATA-3', promotes, 'NK', cell, maturation, and, acts, in, this, lineage, to, specify, distinct, effector, phenotypes])]). relacion([sujeto(['Using', conditional, gene]), verbo([targeting]), complemento([in, 'mice,', we, show, that, 'BMP', receptor, 'IA', is, essential, for, the, differentiation, of, progenitor, cells, of, the, inner, root, sheath, and, hair, shaft])]). relacion([sujeto(['Without', 'BMPRIA', 'activation,', 'GATA-3', is, 'down-regulated', and, its]), verbo([regulated]), complemento([control, of, 'IRS', differentiation, is, compromised])]). relacion([sujeto(['In', 'contrast,', 'Lef1', is, 'up-regulated,', but, its]), verbo([regulated]), complemento([control, of, hair, differentiation, is, still, 'blocked,', and, 'BMPRIA-null', follicles, fail, to, activate, 'Lef1/beta-catenin-regulated', 'genes,', including, keratin, genes])]). relacion([sujeto(['Wnt-mediated', transcriptional, activation, can, be, restored, by, transfecting, 'BMPRIA-null', keratinocytes, with, a, constitutively]), verbo([activated]), complemento(['beta-catenin'])]). relacion([sujeto(['Because', mice, lacking, the, 'BMP', inhibitor, 'Noggin', fail, to]), verbo([express]), complemento(['Lef1,', our, findings, support, a, 'model,', whereby, a, sequential, inhibition, and, then, activation, of, 'BMPRIA', is, necessary, to, define, a, band, of, hair, progenitor, 'cells,', which, possess, enough, 'Lef1', and, stabilized, 'beta-catenin', to, activate, the, hair, specific, keratin, genes, and, generate, the, hair, shaft])]). relacion([sujeto(['Th1', and, 'Th2', cells, arise, from, a, common, precursor, cell, in, response, to]), verbo([triggering]), complemento([through, the, 'TCR', and, cytokine, receptors, for, 'IL-12', or, 'IL-4'])]). relacion([sujeto(['This']), verbo([leads]), complemento([to, activation, of, complex, signaling, 'pathways,', which, are, not, known, in, detail])]). relacion([sujeto(['Disturbances', in, the, balance, between, type, 1, and, type, 2, responses, can]), verbo([lead]), complemento([to, certain, 'immune-mediated', diseases])]). relacion([sujeto(['To', clarify, the, mechanisms, as, to, how, 'IL-12', and, 'IL-4']), verbo([induce]), complemento(['Th1', and, 'Th2', differentiation, and, how, 'TGF-beta', can, inhibit, this, 'process,', we, have, used, oligonucleotide, arrays, to, examine, the, early, polarization, of, 'Th1', and, 'Th2', cells, in, the, presence, and, absence, of, 'TGF-beta'])]). relacion([sujeto(['In', addition, to, genes, previously, implicated, in, the, 'process,', we]), verbo([have]), complemento([identified, 20, genes, with, various, known, and, unknown, functions, not, previously, associated, with, 'Th1/2', polarization])]). relacion([sujeto(['We']), verbo([have]), complemento([also, further, determined, which, genes, are, targets, of, 'IL-12,', 'IL-4,', and, 'TGF-beta', regulation, in, the, cells, induced, to, polarize, to, 'Th1', and, 'Th2', directions])]). relacion([sujeto(['Among', these, genes, are, candidates, that, may]), verbo([modulate]), complemento([the, balance, between, 'Th1', and, 'Th2', responses])]). relacion([sujeto(['How', 'T', cells]), verbo([regulate]), complemento([interleukin, 4, '(', 'IL-4)', expression, is, not, completely, understood])]). relacion([sujeto(['We', show, here, that, 'single-positive', thymocytes]), verbo([express]), complemento(['IL-4,', but, attenuate, 'GATA-3', 'expression,', recruit, 'DNA', methyltransferases, '(', 'Dnmts)', to, the, 'Il4-Il13', locus, and, downregulate, 'IL-4', expression, as, they, mature, into, 'T', cells])]). relacion([sujeto(['Type', 2, polarization, blocks, 'Dnmt1', 'recruitment,']), verbo([enhances]), complemento([histone, 'H3', 'Lys4', methylation, '(', indicative, of, accessible, 'chromatin)', and, initiates, 'DNA', demethylation, of, the, locus])]). relacion([sujeto(['Dnmt1-/-', 'CD4', and, 'CD8', 'T', cells, derepress, 'IL-4', expression, 'considerably,', demethylate, 'DNA', and]), verbo([increase]), complemento(['H3', 'Lys4', methylation, without, affecting, 'GATA-3', 'expression,', demonstrating, that, 'Dnmt1', and, 'DNA', methylation, are, essential, for, proper, 'Il4', regulation])]). relacion([sujeto(['GATA', transcription, factors, 2, and, 3, could, be]), verbo([involved]), complemento([in, modulating, this, 'switch,', because, they, were, shown, to, negatively, regulate, erythropoietin, gene, transcription, through, a, promoter, proximal, 'GATA', site])]). relacion([sujeto(['Although', 'GATA-3', expression, in, hepatocytes]), verbo([increases]), complemento([during, human, 'development,', erythropoietin, mRNA, accumulation, is, unaltered, in, mutant, mice, lacking, 'GATA-3'])]). relacion([sujeto(['We']), verbo([found]), complemento([that, 'GATA-2,', -, 3, ',', -, 4, ',', and, -, 6, are, all, expressed, in, human, hepatocytes, and, that, 'GATA-4', exhibits, the, most, prominent, 'Epo', promoter, binding, activity, in, vitro, and, in, vivo])]). relacion([sujeto(['Inhibition', of, 'GATA-4', expression, by, 'RNA', interference]), verbo([leads]), complemento([to, a, dramatic, reduction, in, 'Epo', gene, transcription, in, 'Hep3B', cells])]). relacion([sujeto(['GATA-3', overexpression, in, 'Yaa', mice]), verbo([led]), complemento([to, simultaneously, elevated, 'Th2', 'Ig', '(', 'IgG1)', and, decreased, 'Th1', 'Ig', '(', 'IgG2a', and, 'IgG3)', production, and, serum, 'IFN-gamma', levels])]). relacion([sujeto(['Although', 'IL-4', production, remained, 'unchanged,', intracellular, cytokine, analyses, demonstrated, that, 'IL-5', was]), verbo([induced]), complemento([and, 'IFN-gamma', was, suppressed, in, stimulated, 'T', cells, from, the, 'GATA-3-transgenic', 'Yaa', mice])]). relacion([sujeto(['These', results, indicated, that, abundant, 'GATA-3', was, unable, to]), verbo([stimulate]), complemento([complete, differentiation, of, 'Th2', cells, but, did, counteract, the, dominance, of, 'Th1', cells, and, alleviated, the, disease, severity, in, 'Yaa', mice])]). relacion([sujeto(['These', data]), verbo([suggest]), complemento([that, transcriptional, regulation, therapy, may, have, potential, as, an, effective, strategy, for, treating, autoimmune, glomerulonephritis])]). relacion([sujeto(['Introduction', of, 'GATA-3', into, 'lineage-committed', 'Th1', cells]), verbo([induced]), complemento([the, expression, of, 'Th2-specific', cytokines, '(', 'IL-4', and, 'IL-5)', and, chemotactic, receptors, '(', 'CCR4,', chemoattractant, 'receptor-homologous', molecule, expressed, on, 'Th2', cells, '(', 'CRTH2)'])]). relacion([sujeto(['However,', these, cells, partially]), verbo([maintained]), complemento([their, 'Th1-specific', profile, '(', 'IFN-gamma', and, 'IL-12Rbeta2', 'expression)'])]). relacion([sujeto(['Conversely,', expression, of, 'T-bet', in, 'lineage-committed', 'Th2', cells]), verbo([caused]), complemento([a, more, profound, switch, to, the, 'Th1', 'phenotype,', including, the, 'up-regulation', of, 'CXCR3', and, 'down-regulation', of, 'CCR4', and, 'CRTH2'])]). relacion([sujeto(['Our', results]), verbo([reveal]), complemento([remarkable, plasticity, in, the, differentiation, programs, of, human, memory, 'T', cells])]). relacion([sujeto(['These', findings]), verbo([have]), complemento([important, implications, in, understanding, the, molecular, mechanisms, of, human, 'T', cell, differentiation, and, for, devising, novel, therapeutic, strategies, aimed, at, immunomodulation, of, skewed, effector, 'T', cell, responses])]). relacion([sujeto(['The', differences, may, yield, insights, into, the, worse, prognosis, and, therapeutic, resistance]), verbo([associated]), complemento([with, clear, cell, carcinomas])]). relacion([sujeto(['A', comparison, of, the, gene, expression, patterns, in, the, ovarian, cancers, to, published, data, of, gene, expression, in, breast, cancers, revealed, a, large, number, of, differentially]), verbo([expressed]), complemento([genes])]). relacion([sujeto(['Among', the, best, discriminators, more, highly]), verbo([expressed]), complemento([in, the, ovarian, carcinomas, were, 'PAX8', '(', paired, box, gene, 8, ')', ',', 'mesothelin,', and, 'ephrin-B1', '(', 'EFNB1)'])]). relacion([sujeto(['Although', estrogen, receptor, was]), verbo([expressed]), complemento([in, both, the, ovarian, and, breast, 'cancers,', genes, that, are, coregulated, with, the, estrogen, receptor, in, breast, 'cancers,', including, 'GATA-3,', 'LIV-1,', and, 'X-box', binding, protein, 1, ',', did, not, show, a, similar, pattern, of, coexpression, in, the, ovarian, cancers])]). relacion([sujeto(['Neonates', are, known, to]), verbo([have]), complemento([poor, cellular, 'immunity,', especially, poor, 'Th1', response])]). relacion([sujeto(['Results', showed, that, 'VZV']), verbo([induced]), complemento([a, dramatic, increase, of, 'IFNgamma', production, by, adult, peripheral, blood, mononuclear, cells, '(', 'PBMC),', whereas, 'VZV', did, not, drive, 'CBMC', to, release, significant, 'IFNgamma', production, '(', 1614.7, +, /, -, 362.0, vs])]). relacion([sujeto(['However,', 'Der', p]), verbo([induced]), complemento([higher, 'IFNgamma', production, by, 'CBMC', than, 'VZV', '(', 298.1, +, /, -, 171.8, vs])]). relacion([sujeto(['In', 'contrast,', 'VZV', did, not]), verbo([induce]), complemento([significant, 'IL-4', production, either, by, 'CBMC', or, by, 'PBMC'])]). relacion([sujeto(['Der', p]), verbo([induced]), complemento([a, comparative, 'IL-4', production, by, 'CBMC', and, 'PBMC', '(', 2.58, +, /, -, 0.84, vs])]). relacion([sujeto(['A', 'real-time', 'RT-PCR', analysis, of, 'IL-4', and, 'IFNgamma', mRNA, expression, showed, that, 'VZV']), verbo([induced]), complemento([a, significantly, higher, 'IFNgamma,', but, not, 'IL-4,', mRNA, expression, in, 'PBMC', than, 'CBMC'])]). relacion([sujeto(['Der', p, did, not]), verbo([induce]), complemento([significant, difference, of, 'IFNgamma', or, 'IL-4', mRNA, expression, in, 'PBMC', and, 'CBMC'])]). relacion([sujeto(['VZV']), verbo([enhanced]), complemento(['Th1-related', transcription, factor, 'T-bet', mRNA, 'expression,', in, association, with, later, 'down-regulation', of, 'Th2-related', 'GATA-3', mRNA, expression, in, 'PBMC'])]). relacion([sujeto(['In', 'contrast,', 'Der', p]), verbo([induced]), complemento([an, early, 'GATA-3', expression, and, later, 'T-bet', expression, in, 'CBMC'])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, different, antigens, trigger, various, 'Th1/Th2', reactions, in, 'PBMC', and, 'CBMC', resulting, from, kinetic, changes, of, 'T-bet/GATA-3', expression])]). relacion([sujeto(['The', differentiation, of, naive, 'T-helper', '(', 'Th)', cells, towards, 'Th1', or, 'Th2', cells, is]), verbo([regulated]), complemento([by, the, transcription, factors, 'T-box', expressed, in, 'T-cells', '(', 'T-bet)', and, 'GATA-binding', 'protein-3', '(', 'GATA-3)'])]). relacion([sujeto([10, /, 'Rag2(-/-)', transgenic, mice, and, control, 'BioBreeding', '(', 'BBc)', 'Wistar', rat, splenic, 'T', cells]), verbo([stimulated]), complemento([under, 'Th1', or, 'Th2', conditions])]). relacion([sujeto(['T-bet', gene, expression, was, not]), verbo([maintained]), complemento([in, fully, polarized, rat, 'Th1', cells, whereas, 'GATA-3', gene, expression, was, maintained, in, 'long-term', polarized, rat, 'Th2', 'cells,', indicating, that, maintenance, of, 'Th1/Th2', status, occurred, more, as, a, result, of, altered, 'GATA-3', mRNA, expression, than, 'T-bet'])]). relacion([sujeto(['These', transcription, factors, are, 'up-regulated', in, several, cells, that, produce, type, 1, and, type, 2, cytokines, and, can, be, analyzed, readily, by, 'RT-PCR', using, total, 'RNA', isolated, from, mixed, cell, populations, or, cultured, splenocytes, thereby]), verbo([providing]), complemento([a, surrogate, marker, of, 'Th1/Th2', cytokine, balance, under, a, variety, of, conditions])]). relacion([sujeto(['GATA-3', plays, a, central, role, in]), verbo([regulating]), complemento(['Th1', and, 'Th2', cell, differentiation])]). relacion([sujeto(['Upon', interleukin, '(', 'IL)-4']), verbo([binding]), complemento([to, its, 'receptor,', 'GATA-3', is, induced, through, the, action, of, 'Stat6'])]). relacion([sujeto(['GATA-3']), verbo([regulates]), complemento(['Th2', cytokine, expression, not, only, at, the, transcription, 'level,', such, as, directly, binding, to, the, promoters, of, the, 'IL-5', and, 'IL-13', 'gene,', but, also, by, the, involvement, in, the, remodeling, of, the, chromatin, structure, and, opening, the, 'IL-4', locus])]). relacion([sujeto(['Steroidogenesis', is, a, tightly]), verbo([regulated]), complemento([process, that, is, dependent, on, pituitary, hormones])]). relacion([sujeto(['In', steroidogenic, 'tissues,', hormonal, stimulation]), verbo([triggers]), complemento([activation, of, an, intracellular, signalling, pathway, that, typically, involves, cAMP, 'production,', activation, of, 'PKA,', and, phosphorylation, of, target, transcription, factors])]). relacion([sujeto(['In', the, classic, cAMP, signalling, 'pathway,', phosphorylation, of, 'CREB', '(', cAMP, response, element, '(', 'CRE)-binding', 'protein)', and, its, subsequent]), verbo([binding]), complemento([to, 'cAMP-response', elements, '(', 'CREs)', in, the, regulatory, regions, of, target, genes, play, a, key, role, in, mediating, cAMP, responsiveness])]). relacion([sujeto(['However,', the, cAMP, responsive, regions, of, several, genes]), verbo([expressed]), complemento([in, steroidogenic, tissues, do, not, contain, consensus, 'CREs', indicating, that, other, transcription, factors, are, also, involved])]). relacion([sujeto(['We']), verbo([have]), complemento([been, studying, the, role, played, by, the, 'GATA', family, of, transcription, factors])]). relacion([sujeto(['GATA', factors, are]), verbo([expressed]), complemento([in, a, variety, of, tissues, including, the, adrenals, and, gonads])]). relacion([sujeto(['Since', the, regulatory, regions, of, several, steroidogenic, genes, contain, 'GATA', 'elements,', we]), verbo([have]), complemento([proposed, that, 'GATA', 'factors,', particularly, 'GATA-4', and, 'GATA-6,', might, represent, novel, downstream, effectors, of, hormonal, signalling, in, steroidogenic, tissues])]). relacion([sujeto(['In', vitro, experiments]), verbo([have]), complemento([revealed, that, 'GATA-4', is, indeed, phosphorylated, in, steroidogenic, cells, and, that, phosphorylation, levels, are, rapidly, induced, by, cAMP])]). relacion([sujeto(['GATA-4', phosphorylation, is]), verbo([mediated]), complemento([by, 'PKA'])]). relacion([sujeto(['Phosphorylation']), verbo([increases]), complemento(['GATA-4', 'DNA-binding', activity, and, enhances, its, transcriptional, properties, on, multiple, steroidogenic, promoters])]). relacion([sujeto(['We', now, define, a, new, molecular, mechanism, whereby, 'phospho-GATA', factors, contribute, to]), verbo([increased]), complemento([transcription, of, steroidogenic, genes, in, response, to, hormonal, stimulation])]). relacion([sujeto(['Developing', 'Tc2', cells]), verbo([expressed]), complemento([lower, 'GATA3', levels, and, dramatically, increased, levels, of, repressor, of, 'GATA', '(', 'ROG)'])]). relacion([sujeto(['A', 'ROG', response, element, in, the, 'IL-13', gene, exon, 4, displayed, 'Tc2-specific']), verbo([binding]), complemento([of, 'ROG,', 'HDAC1,', and, 'HDAC2', and, exhibited, repression, of, 'IL-4', gene, activation])]). relacion([sujeto(['Thus,', 'ROG', may]), verbo([confer]), complemento(['CD8', 'T', 'cell-specific', repression, of, histone, hyperacetylation, and, activation, of, the, 'IL-4', gene, locus])]). relacion([sujeto(['Surprisingly,', this, transcription, factor, is, essential, for, stem, cell, lineage, determination, in, 'skin,', where, it, is]), verbo([expressed]), complemento([at, the, onset, of, epidermal, stratification, and, 'IRS', specification, in, follicles])]). relacion([sujeto(['Curiously,', some, 'GATA-3-null', progenitor, cells]), verbo([expressed]), complemento([mixed, 'IRS', and, hair, shaft, markers])]). relacion([sujeto(['Allergic', asthma, is, characterized, by, airway, 'hyperresponsiveness,', 'eosinophilia,', and, mucus, accumulation, and, is]), verbo([associated]), complemento([with, increased, 'IgE', concentrations])]). relacion([sujeto(['We', demonstrate, here, that, peroxisome, 'proliferator-activated', receptors, '(', 'PPARs),', 'PPAR-alpha', and, 'PPAR-gamma,', which]), verbo([have]), complemento([been, shown, recently, to, be, involved, in, the, regulation, of, various, cell, types, within, the, immune, 'system,', decrease, 'antigen-induced', airway, 'hyperresponsiveness,', lung, 'inflammation,', 'eosinophilia,', cytokine, 'production,', and, 'GATA-3', expression, as, well, as, serum, levels, of, 'antigen-specific', 'IgE', in, a, murine, model, of, human, asthma])]). relacion([sujeto(['In', 'addition,', we, demonstrate, that, 'PPAR-alpha', and, -, gamma, are]), verbo([expressed]), complemento([in, eosinophils, and, their, activation, inhibits, in, vitro, chemotaxis, and, 'antibody-dependent', cellular, cytotoxicity])]). relacion([sujeto(['Thus,', 'PPAR-alpha', and, -, gamma, '(', 'co)agonists', might, be, of, therapeutic, interest, for, the, regulation, of, allergic, or, inflammatory, reactions, by]), verbo([targeting]), complemento([both, regulatory, and, effector, cells, involved, in, the, immune, response])]). relacion([sujeto(['Th2', cytokine, is, predominant, in, tumor, patients, and, was]), verbo([found]), complemento([to, be, associated, with, tumor, progression])]). relacion([sujeto(['AG']), verbo([enhanced]), complemento([culture, supernatant, and, gene, expression, levels, of, 'Th1', cytokine, '(', 'IFNgamma', and, 'IL-2)', and, its, transcript, factor, '(', 'T-bet),', and, reduced, those, of, 'Th2', cytokines, in, cultured, 'PBMNC', of, lung, cancer, patients])]). relacion([sujeto(['In', the, second, 'system,', functional, differentiation, was]), verbo([induced]), complemento([in, purified, naive, 'CD4', 'T', cells, from, 'DO-11'])]). relacion([sujeto(['In', both, 'systems,', 'all-trans-RA', at, &, 'gt;', or, =, 1, nM, concentrations]), verbo([suppressed]), complemento(['Th1', 'development,', but, enhanced, 'Th2', development])]). relacion([sujeto(['The', presence, of, 'RA', during, the, initial, stimulation, period, often]), verbo([suppressed]), complemento(['Th2', development])]). relacion([sujeto(['The', 'RA', receptor, '(', 'RAR)', 'antagonists,', 'LE540', and, 'LE135,', but, not, the, retinoic, 'X', receptor, '(', 'RXR)', 'antagonist,', 'PA452,']), verbo([inhibited]), complemento([the, effect, of, 'RA', on, 'Th1/Th2', development])]). relacion([sujeto(['The', 'RXR', agonists]), verbo([enhanced]), complemento([the, effect, of, the, 'RAR', agonists, only, 'slightly,', if, at, all])]). relacion([sujeto(['These', results, indicate, 'that,', via, 'RAR,', 'RA', directly]), verbo([suppresses]), complemento(['Th1', development, and, directly, enhances, 'Th2', development, with, its, timely, addition])]). relacion([sujeto(['Here', we, demonstrate, that, ectopic, expression, of, the, transcription, factors, 'C/EBPalpha,', 'GATA1,', 'GATA2', and, 'GATA3', strongly]), verbo([promoted]), complemento([in, vitro, macrophage, differentiation, and, myeloid, colony, formation, of, 'Pax5(-/-)', 'pro-B', cells])]). relacion([sujeto(['These', data, identify, the, 'Pax5(-/-)', 'pro-B', cells, as, lymphoid, progenitors, with, a, latent, myeloid, potential, that, can, be, efficiently]), verbo([activated]), complemento([by, myeloid, transcription, factors])]). relacion([sujeto(['The', same, regulators, were, unable, to]), verbo([induce]), complemento([a, myeloid, lineage, switch, in, 'Pax5(+/+)', 'pro-B', 'cells,', indicating, that, 'Pax5', dominates, over, myeloid, transcription, factors, in, 'B-lymphocytes'])]). relacion([sujeto(['Interleukin-4', '(', 'IL-4)', is, crucial, for, the, differentiation, of, naive, 'T', helper, '(', 'T(H))', cells, into, the, 'T(H)2', effector, cells, that]), verbo([promote]), complemento([humoral, '(', 'antibody)', immunity, and, provide, protection, against, intestinal, helminths])]). relacion([sujeto(['IL-4', also]), verbo([has]), complemento([a, central, role, in, the, pathogenesis, of, allergic, inflammation])]). relacion([sujeto(['Many', transcription, factors, are]), verbo([involved]), complemento([in, the, regulation, of, expression, of, the, gene, encoding, 'IL-4'])]). relacion([sujeto(['Initiation', of, transcription, of, the, gene, encoding, 'IL-4', in, naive, 'T(H)', cells, is]), verbo([regulated]), complemento([by, the, 'T(H)2-specific', transcription, factor, 'GATA3,', whereas, acute, expression, of, the, gene, encoding, 'IL-4', in, 'T(H)2', cells, is, mediated, by, 'inducible,', ubiquitous, transcription, factors, after, antigen, encounter])]). relacion([sujeto(['The', homeobox, 'Six', 'genes,', homologues, to, 'Drosophila', sine, oculis, '(', 'so)', 'gene,', are]), verbo([expressed]), complemento([in, multiple, organs, during, mammalian, development])]). relacion([sujeto(['However,', their, roles, during, auditory, system, development]), verbo([have]), complemento([not, been, studied])]). relacion([sujeto(['We']), verbo([report]), complemento([that, 'Six1', is, required, for, mouse, auditory, system, development])]). relacion([sujeto(['Six1', is, also]), verbo([expressed]), complemento([in, the, vestibuloacoustic, ganglion])]). relacion([sujeto([5, ',', 'Six1', is]), verbo([expressed]), complemento([in, all, sensory, epithelia, of, the, inner, ear])]). relacion([sujeto(['Using', recently, generated, 'Six1', mutant, 'mice,', we]), verbo([found]), complemento([that, all, 'Six1(+/-)', mice, showed, some, degree, of, hearing, loss, because, of, a, failure, of, sound, transmission, in, the, middle, ear])]). relacion([sujeto(['By', 'contrast,', 'Six1(-/-)', mice, displayed, malformations, of, the, auditory, system]), verbo([involving]), complemento([the, 'outer,', middle, and, inner, ears])]). relacion([sujeto(['The', inner, ear, development, in, 'Six1(-/-)', embryos]), verbo([arrested]), complemento([at, the, otic, vesicle, stage, and, all, components, of, the, inner, ear, failed, to, form, due, to, increased, cell, death, and, reduced, cell, proliferation, in, the, otic, epithelium])]). relacion([sujeto(['Because', we, previously]), verbo([reported]), complemento([that, 'Six1', expression, in, the, otic, vesicle, is, 'Eya1', 'dependent,', we, first, clarified, that, 'Eya1', expression, was, unaffected, in, 'Six1(-/-)', otic, 'vesicle,', further, demonstrating, that, the, 'Drosophila', 'Eya-Six', regulatory, cassette, is, evolutionarily, conserved, during, mammalian, inner, ear, development])]). relacion([sujeto(['We', also, analyzed, several, other, otic, markers, and]), verbo([found]), complemento([that, the, expression, of, 'Pax2', and, 'Pax8', was, unaffected, in, 'Six1(-/-)', otic, vesicle])]). relacion([sujeto(['By', 'contrast,', 'Six1', is]), verbo([required]), complemento([for, the, activation, of, 'Fgf3', expression, and, the, maintenance, of, 'Fgf10', and, 'Bmp4', expression, in, the, otic, vesicle])]). relacion([sujeto(['Furthermore,']), verbo([loss]), complemento([of, 'Six1', function, alters, the, expression, pattern, of, 'Nkx5'])]). relacion([sujeto([1, and, 'Gata3,', indicating, that, 'Six1', is]), verbo([required]), complemento([for, regional, specification, of, the, otic, vesicle])]). relacion([sujeto(['Finally,', our, data]), verbo([suggest]), complemento([that, the, interaction, between, 'Eya1', and, 'Six1', is, crucial, for, the, morphogenesis, of, the, cochlea, and, the, posterior, ampulla, during, inner, ear, development])]). relacion([sujeto(['The', 'Th2', cytokine, genes, 'IL4,', 'IL5,', and, 'IL13', are, clustered, and]), verbo([expressed]), complemento([in, a, cell, 'lineage-specific', manner])]). relacion([sujeto(['IL4', promoter, activity, in, effector, 'CD4', 'T', cells, from, these, transgenic, mice, was, 'strong,', 'Th2', 'specific,', and, copy, number, 'dependent,']), verbo([suggesting]), complemento([the, presence, of, an, 'LCR', in, the, locus])]). relacion([sujeto(['Expression', of, the, 'IL4', 'promoter-luciferase', reporter, was, transactivated, by, 'GATA-3', irrespective, of, position, in, the, 'locus,']), verbo([suggesting]), complemento([the, global, nature, of, this, regulation])]). relacion([sujeto(['The', 'LCR', 'itself,', 'however,', does, not]), verbo([respond]), complemento([directly, to, 'GATA-3'])]). relacion([sujeto(['GATA-3', is]), verbo([expressed]), complemento([at, higher, levels, in, 'CD4', than, in, 'CD8', 'SP', thymocytes])]). relacion([sujeto(['Here', we, show, that, upregulation, of, 'GATA-3', expression, in, 'DP', thymocytes, is]), verbo([triggered]), complemento([by, 'TCR', 'stimulation,', and, the, extent, of, upregulation, correlates, with, the, strength, of, the, 'TCR', signal])]). relacion([sujeto(['Overexpression', of, 'GATA-3', or, a, partial, 'GATA-3', agonist, during, positive, selection]), verbo([inhibits]), complemento(['CD8', 'SP', cell, development, but, is, not, sufficient, to, divert, class, 'I-restricted', 'T', cell, precursors, to, the, 'CD4', lineage])]). relacion([sujeto(['Conversely,', expression, of, the, 'GATA-3', antagonist, 'ROG', or, of, a, 'GATA-3', siRNA, hairpin, markedly]), verbo([enhances]), complemento([development, of, 'CD8', 'SP', cells, and, reduces, 'CD4', 'SP', development])]). relacion([sujeto(['If', 'co-ordinate', regulation, were, to, take, 'place,', it, might, be, argued, that, similar, factors, might, be]), verbo([involved]), complemento([in, expression, of, all, of, the, cytokines])]). relacion([sujeto(['Emerging', data, on, 'c-Maf', and, 'GATA3', regulation, of, 'IL-4', and, 'IL-5', respectively, argues, that, diverse, proteins, may, be]), verbo([required]), complemento([for, transcriptional, activation])]). relacion([sujeto(['Alternatively,', these, factors, may, be, responsible, for]), verbo([regulating]), complemento([transcriptional, 'competence,', allowing, fine, control, over, generation, of, particular, cytokines, depending, upon, recognition, of, physiological, cues])]). relacion([sujeto(['If', competent, for, 'transcription,', common, 'factors,', such, as, members, of, the, 'NFAT', 'and/or', 'AP-1', 'families,', may, operate, to]), verbo([regulate]), complemento([cytokine, levels])]). relacion([sujeto(['To', support, 'this,', we]), verbo([have]), complemento([recently, identified, a, conserved, palindrome, located, within, the, promoters, of, the, different, 'Th2-type', 'cytokines,', which, acts, as, an, enhancer, of, transcription])]). relacion([sujeto(['Central', to, the, capacity, to]), verbo([express]), complemento(['Th2', cytokines, is, likely, to, be, the, ability, to, remodel, chromatin, at, the, locus])]). relacion([sujeto(['It', remains, to, be, determined, whether, a, single, 'factor,', or, combination, of, factors]), verbo([acts]), complemento([to, regulate, this, event])]). relacion([sujeto([whether, 'IL-4', and, 'IL-13', may, be, within, open, chromatin, and, 'IL-5', in, a, closed, 'environment,', and, whether, there, is, a, hierarchy, which, determines, whether, particular, cytokines, are, preferentially]), verbo([expressed]), complemento([irrespective, of, competence])]). relacion([sujeto(['We']), verbo([found]), complemento([a, tight, correlation, among, the, levels, of, 'H4/inducible', costimulator, '(', 'ICOS)', 'expression,', 'IL-4', 'production,', and, 'GATA-3', 'induction,', using, activated, 'CD4(+)', 'T', cells, obtained, from, six, different, murine, strains])]). relacion([sujeto(['BALB/c-activated', 'CD4(+)', 'T', cells]), verbo([expressed]), complemento([approximately, 10, -, fold, more, 'H4/ICOS', on, their, surfaces, and, produced, approximately, 10, -, fold, more, 'IL-4', upon, restimulation, than, 'C57BL/6-activated', 'CD4(+)', 'T', cells])]). relacion([sujeto(['Neutralization', of, 'IL-4', with, mAbs, in, culture, of, 'BALB/c', naive, 'CD4(+)', 'T', cells, strongly, 'down-regulated', both, 'H4/ICOS', expression, on]), verbo([activated]), complemento(['CD4(+)', 'T', cells, and, 'IL-4', production, upon, subsequent, restimulation])]). relacion([sujeto(['In', 'addition,', retroviral, expression, of, 'GATA-3', during, the, stimulation, of, naive, 'CD4(+)', 'T', cells, from, 'C57BL/6', or, 'IL-4(-/-)', mice]), verbo([increased]), complemento(['H4/ICOS', expression, on, activated, 'CD4(+)', 'T', cells])]). relacion([sujeto(['A', similar, effect, of, 'IL-2', in, the, primary, culture, of, 'BALB/c', naive, 'CD4(+)', 'T', cells, appeared, to, be]), verbo([mediated]), complemento([by, 'IL-4,', the, production, of, which, was, regulated, by, 'IL-2'])]). relacion([sujeto(['These', data]), verbo([suggest]), complemento([that, 'IL-4', induced, by, 'IL-2', is, critical, to, the, maintenance, of, high, 'H4/ICOS', expression, on, 'BALB/c-activated', 'CD4(+)', 'T', cells])]). relacion([sujeto(['Naive', 'T', cells, from, transgenic, mice]), verbo([expressing]), complemento([a, dominant, interfering, form, of, 'Runx1', exhibited, enhanced, interleukin, 4, production, and, efficient, 'Th2', differentiation])]). relacion([sujeto(['In', 'contrast,', transduction, of, 'Runx1', into, 'wild-type', 'T', cells]), verbo([caused]), complemento([a, complete, attenuation, of, 'Th2', differentiation, and, was, accompanied, by, the, cessation, of, 'GATA3', expression])]). relacion([sujeto(['We', conclude, that, 'Runx1', plays, a, novel, role, as, a, negative, regulator, of, 'GATA3', 'expression,', thereby]), verbo([inhibiting]), complemento([the, 'Th2', cell, differentiation])]). relacion([sujeto(['Antigen', and, cytokine, receptor, signals]), verbo([act]), complemento([in, synergy, to, direct, the, differentiation, of, 'CD4+', 'T', cells])]). relacion([sujeto(['These', signals, initiate, reciprocal, activation, and, silencing, of, the, 'interferon-gamma', '(', 'IFN-gamma)', and, interleukin, 4, '(', 'IL-4)', cytokine, gene, 'loci,', changes, that, are, heritably]), verbo([maintained]), complemento([in, the, resulting, 'T', helper, type, 1, '(', 'T(H)1)', or, 'T(H)2', cells, and, their, progeny])]). relacion([sujeto(['Recent', studies]), verbo([have]), complemento([begun, to, elucidate, the, molecular, mechanisms, that, establish, and, maintain, polarized, cytokine, gene, 'expression,', and, thus, the, cellular, identity, of, differentiated, helper, 'T', cells])]). relacion([sujeto(['The', interleukin, 13, alpha, 2, receptor, '(', 'IL-13Ra2)']), verbo([has]), complemento([been, shown, to, be, expressed, in, most, malignant, glioblastoma, cells])]). relacion([sujeto(['Recent', studies]), verbo([suggest]), complemento([that, 'IL-13Ra2', serves, as, a, dominant, negative, inhibitor, or, a, decoy, receptor, for, 'IL-13'])]). relacion([sujeto(['Several', putative, transcriptional, factor]), verbo([binding]), complemento([sites, for, nuclear, factor, of, activated, 'T', cells, 1, ',', 'AP1', '(', 'c-JUN', and, 'c-FOS),', 'AP2,', 'GABP,', 'OCT1,', 'GATA3,', 'PRE,', and, 'C-ETS1', were, predicted, in, the, promoter, region])]). relacion([sujeto(['The', different, secreted, alkaline, phosphate, activities, among, these, 3, cell, lines]), verbo([suggest]), complemento([that, the, expression, of, human, 'IL-13Ra2', is, regulated, at, the, transcriptional, level])]). relacion([sujeto(['This', 64, -, bp, sequence, contains, 'cis-elements', for, 'AP1,']), verbo([nuclear]), complemento([factor, of, activated, 'T', 'cells,', and, 'AP2'])]). relacion([sujeto(['The', possible, role, of, 'AP1', in, the, regulation, of, human, 'IL-13Ra2', promoter, activity, was]), verbo([suggested]), complemento([by, in, vitro, mutagenesis, and, 'c-JUN', 'N-terminal', kinase, inhibition, analysis])]). relacion([sujeto(['Furthermore,', higher, numbers, of, cells, producing, 'GATA-3,', 'c-MAF,', and, signal, transducer, and, activator, of, transcription, factor, '(', 'STAT)-6,', which, are, transcription, factors, '(', 'TFs)', that, are, implicated, in, the, regulation, and, signaling, of, the, 'Th2', 'cytokines,']), verbo([have]), complemento([been, observed, in, bronchial, biopsy, specimens, from, asthmatic, patients, but, not, in, those, of, healthy, control, subjects])]). relacion([sujeto(['We', examined, whether, these, mediators, also, can, be, detected, in]), verbo([induced]), complemento([sputum])]). relacion([sujeto(['Immunoreactivity', for, 'IL-4Ralpha,', 'IL-5Ralpha,', 'GATA-3,', 'c-MAF,', and, 'STAT-6', was, investigated, in, samples, of]), verbo([induced]), complemento([sputum, from, asthmatic, patients, '(', n, =, 8, ')', and, healthy, control, subjects, '(', n, =, 8, ')'])]). relacion([sujeto(['Our', results, showed, that, the, numbers, of, cells]), verbo([expressing]), complemento(['IL-4', receptor, alpha, '(', 'Ralpha)', and, 'IL-5Ralpha', were, higher, in, samples, from, asthmatic, patients, compared, to, those, of, control, subjects, '(', p, &, 'lt;', 0.01, ')'])]). relacion([sujeto(['More', cells, exhibiting, 'GATA-3,', 'c-MAF,', and, 'STAT-6', immunoreactivity, also, were]), verbo([found]), complemento([in, asthmatic, patients, vs, those, in, control, subjects, '(', p, &, 'lt;', 0.005, ')'])]). relacion([sujeto(['This', study, demonstrated, that]), verbo([induced]), complemento([sputum, provides, sufficient, sensitivity, for, examining, the, pathways, of, cytokine, 'signaling,', cytokine, receptor, 'signaling,', and, intracellular, signaling])]). relacion([sujeto(['Furthermore,', these, data, show, correlations, between, the, expression, of, 'Th2', cytokine, receptors, and]), verbo([associated]), complemento(['TFs', in, the, human, 'lung,', which, has, not, been, documented, previously])]). relacion([sujeto(['Mice', were, infected, with, the, intestinal, nematode, 'Heligmosomoides', polygyrus, to]), verbo([induce]), complemento(['Th2', immune, responses])]). relacion([sujeto(['polygyrus-infected', 'mice,', was, significantly]), verbo([enhanced]), complemento([in, 'GATA-3-transgenic', mice, compared, with, nontransgenic, control, mice])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, 'GATA-3', promotes, 'IL-5', and, 'IL-13', 'production,', and, that, the, function, of, these, cytokines, results, in, eosinophilia, and, 'hyper-IgE,', respectively])]). relacion([sujeto(['Permanent', hearing, and, balance, deficits, can, be]), verbo([triggered]), complemento([by, genetic, susceptibilities, or, environmental, factors, such, as, infection])]). relacion([sujeto(['Unlike', mammalian, hair, cells, that]), verbo([have]), complemento([a, limited, capacity, for, 'regeneration,', the, vestibular, organ, of, the, avian, ear, is, constantly, undergoing, hair, cell, 'regeneration,', whereas, the, avian, cochlea, undergoes, regeneration, only, when, hair, cells, are, damaged])]). relacion([sujeto(['In', order, to]), verbo([gain]), complemento([insights, into, the, genetic, programs, that, govern, the, regenerative, capacity, of, hair, 'cells,', we, interrogated, custom, human, cDNA, microarrays, with, sensory, epithelial, cell, targets, from, avian, inner, ears])]). relacion([sujeto(['The', arrays, contained, probes, from]), verbo([conserved]), complemento([regions, of, approximately, 400, genes, expressed, primarily, in, the, inner, ear, and, approximately, 1500, transcription, factors, '(', 'TF)'])]). relacion([sujeto(['Twenty', differentially]), verbo([expressed]), complemento(['TFs', map, to, chromosomal, regions, harboring, uncloned, human, deafness, 'loci,', and, represent, novel, candidates, for, hearing, loss])]). relacion([sujeto(['The', approach, described, here, also, illustrates, the, power, of, utilizing]), verbo([conserved]), complemento([human, cDNA, probes, for, 'cross-species', comparisons])]). relacion([sujeto(['The', normal, immunoregulatory, mechanisms, that]), verbo([maintain]), complemento([homeostasis, in, the, intestinal, 'mucosa,', despite, continuous, provocation, by, environmental, 'antigens,', are, jeopardized, in, inflammatory, bowel, diseases])]). relacion([sujeto(['Although', previous, studies]), verbo([have]), complemento([suggested, that, intestinal, intraepithelial, lymphocytes, prevent, spontaneous, intestinal, 'inflammation,', there, is, limited, knowledge, about, the, characteristics, of, regulatory, cells, in, the, intestinal, intraepithelial, lymphocytes, population])]). relacion([sujeto(['Here', we, show, that, 'CD4(+)CD8', alpha, 'alpha(+)', 'double-positive', cells, present, in, the, intestinal, intraepithelial, lymphocytes, population, can]), verbo([suppress]), complemento(['T', helper, 1, -, induced, intestinal, inflammation, in, an, 'IL-10-dependent', fashion])]). relacion([sujeto(['CD4(+)', 'T', cells]), verbo([stimulated]), complemento([along, the, 'Th2', but, not, the, 'Th1', 'lineage,', when, transferred, to, 'RAG-1-/-', 'mice,', acquire, 'CD8', alpha, alpha, expression, on, reaching, the, intestinal, 'epithelium,', and, on, arrival, 'there,', augment, their, production, of, 'IL-10'])]). relacion([sujeto(['Both', 'CD8', alpha, alpha, acquisition, and, 'IL-10', production, depend, critically, on, the, 'NF-kappa', 'B-GATA-3-axis', that, we]), verbo([have]), complemento([previously, shown, is, essential, for, differentiation, to, the, 'Th2', phenotype, and, for, the, induction, of, airway, inflammation])]). relacion([sujeto(['Results', from, experimental, 'models,', in, vitro, 'studies,', and, clinical, data, indicate, that, granulocyte, 'colony-stimulating', factor, '(', 'G-CSF)', stimulation, alters, 'T-cell', function, and]), verbo([induces]), complemento(['Th2', immune, responses])]). relacion([sujeto(['In', contrast, to, the, general, belief, that, 'G-CSF']), verbo([acts]), complemento([exclusively, on, 'T', cells, via, monocytes, and, dendritic, 'cells,', our, results, clearly, show, the, expression, of, the, 'G-CSF', receptor, in, class, 'I-', and, 'II-', restricted, 'T', cells, at, the, 'single-cell', level, both, in, vivo, and, in, vitro])]). relacion([sujeto(['Expression', profiling, of, 'T', cells, from, 'G-CSF-treated', stem, cell, donors, allowed, identification, of, several, immune, modulatory, 'genes,', which, are]), verbo([regulated]), complemento([upon, 'G-CSF', administration, in, vivo, '(', 'eg,', 'LFA1-alpha,', 'ISGF3-gamma)', and, that, are, likely, responsible, for, the, reduced, reactivity, 'and/or', alloreactivity])]). relacion([sujeto(['Most', 'importantly,', the, induction, of, 'GATA-3,', the, master, transcription, factor, for, a, 'Th2', immune, 'response,', could, be, demonstrated, in, 'T', cells, upon, 'G-CSF', treatment, in, vivo, accompanied, by, an]), verbo([increase]), complemento([of, spontaneous, 'interleukin-4', secretion])]). relacion([sujeto(['Hence,', 'G-CSF', is, a, strong, immune, regulator, of, 'T', cells, and, a, promising, therapeutic, tool, in, acute, 'graft-versus-host', disease, as, well, as, in, conditions]), verbo([associated]), complemento([with, 'Th1/Th2', 'imbalance,', such, as, bone, marrow, failure, syndromes, and, autoimmune, diseases])]). relacion([sujeto(['At', week, 14, postinfection, '(', 'mid-acute', 'phase),', mRNAs, for, leukocyte, markers, '(', 'CD3,', 'CD4,', 'CD8),', type, 1, cytokines, and, related, transcription, factors, '(', 'IFN-gamma,', 'TNF-alpha,', 'STAT4,', 'T-bet),', and, 'IL-10', were]), verbo([increased]), complemento([in, livers, from, resolving, 'infections,', but, mRNAs, of, other, type, 1, '(', 'IL-2)', and, type, 2, '(', 'IL-4,', 'STAT6,', and, 'GATA3', markers, remained, at, baseline, levels])]). relacion([sujeto(['In', 'conclusion,', the, onset, and, maintenance, of, neonatal, chronic, 'WHV', infection, are, not]), verbo([associated]), complemento([with, antagonistic, type, 2, immunoregulation, of, type, 1, responses, in, liver])]). relacion([sujeto(['Accordingly,', chronicity, develops, in, association, with, a, primary, deficiency, in, the, intrahepatic, 'CD', 'responses,', especially]), verbo([involving]), complemento(['CD8(+)', 'T', 'lymphocytes,', and, in, both, extracellular, '(', 'cytokine)', and, intracellular, '(', 'transcriptional)', type, 1, response, mediators])]). relacion([sujeto(['This']), verbo([has]), complemento([relevant, implications, for, future, treatment, of, chronic, hepatitis, 'B', virus, '(', 'HBV)', infection, in, humans])]). relacion([sujeto(['To', further, understand, the, interaction, among, 'GATA-3,', 'Stat4,', and, 'T-bet', in, helper, 'T', cell, 'development,', we, first, showed, that, retroviral, expression, of, 'GATA-3', in, developing, 'Th1', cells]), verbo([suppresses]), complemento(['Th1', development, through, downregulation, of, 'Stat4', rather, through, downregulation, of, the, 'IL-12Rbeta2', chain])]). relacion([sujeto(['Correspondingly,', 'Stat4', levels, are, greatly]), verbo([suppressed]), complemento([during, physiological, 'Th2', development])]). relacion([sujeto(['Several', 'T(H)2', cytokines]), verbo([have]), complemento([the, potential, to, modulate, airway, 'inflammation,', particularly, 'IL-13,', which, induces, airway, hyperresponsiveness, independently, of, 'IgE', and, eosinophilia, in, animal, models])]). relacion([sujeto(['Using', primary, murine, 'CD4(+)', 'T', 'lymphocytes,', we, show, in, this, study, that, inhibition, of, protein, kinase, 'A', '(', 'PKA)', activity, in, 'Th2', effector, cells, impairs, 'IL-5', 'synthesis,', whereas, the, expression, of, 'PKA', catalytic, subunit, alpha]), verbo([enhances]), complemento(['IL-5', synthesis, in, 'Th0', cells])]). relacion([sujeto(['These', data, demonstrate, that, activation, of, 'PKA', in, 'Th', effector, cells]), verbo([induces]), complemento([the, 'IL-5', gene, expression, in, a, 'GATA-3-dependent', manner])]). relacion([sujeto(['We']), verbo([have]), complemento([investigated, the, mechanism, for, how, 'BCL-6', regulates, 'Th2', cell, differentiation, and, have, found, that, 'IL-6', signaling, can, promote, dramatically, increased, levels, of, 'Th2', differentiation, in, 'BCL-6(-/-)', 'CD4', 'T', cells, compared, with, 'wild-type', 'CD4', 'T', cells])]). relacion([sujeto(['IL-6', can]), verbo([induce]), complemento([a, low, level, of, 'Th2', cytokine, expression, in, 'BCL-6(-/-)STAT6(-/-)', cells, but, not, in, 'STAT6(-/-)', cells])]). relacion([sujeto(['Since', the, promoters, for, 'Th2', cytokines, such, as, 'IL-4,', 'IL-5,', 'IL-10,', and, 'IL-13', do, not, contain, consensus, 'BCL-6', 'DNA']), verbo([binding]), complemento(['sites,', we, investigated, whether, 'BCL-6', might, regulate, the, 'GATA-3', transcription, factor, that, activates, the, expression, of, multiple, 'Th2', cytokines])]). relacion([sujeto(['Consistent', with, the, idea, that, 'BCL-6', represses, 'GATA-3', 'expression,', we]), verbo([found]), complemento([that, 'GATA-3', levels, are, 'up-regulated', in, 'BCL-6(-/-)STAT6(-/-)', 'CD4', 'T', cells, compared, with, 'STAT6(-/-)', 'CD4', 'T', cells])]). relacion([sujeto(['Retrovirus-mediated', expression, of, 'BCL-6', in, 'BCL-6(-/-)STAT6(-/-)', 'T', cells, as, well, as, developing, 'wild-type', 'Th2', cells]), verbo([leads]), complemento([to, a, potent, repression, of, 'IL-4', and, 'IL-10', secretion])]). relacion([sujeto(['Retrovirus-mediated', expression, of, 'BCL-6', in, both, 'BCL-6(-/-)STAT6(-/-)', and, 'wild-type', 'T', cells, also]), verbo([leads]), complemento([to, a, significant, decrease, in, 'GATA-3', protein, levels])]). relacion([sujeto(['Surprisingly,', 'BCL-6', does, not, appear, to]), verbo([regulate]), complemento(['GATA-3', mRNA, levels, and, thus, 'BCL-6', appears, to, regulate, 'GATA-3', expression, at, a, posttranscriptional, level])]). relacion([sujeto(['Regulation', of, 'GATA-3', protein, levels, is, likely, a, key, mechanism, for, how, 'BCL-6']), verbo([regulates]), complemento(['Th2', cytokine, expression, and, 'Th2', differentiation, independently, of, 'STAT6'])]). relacion([sujeto(['SPACRCAN', is, a, novel, proteoglycan, present, in, the, interphotoreceptor, matrix, '(', 'IPM)', of, the, rat, and, human, retina, that, resists, aqueous, extraction, through, its]), verbo([binding]), complemento([to, hyaluronan])]). relacion([sujeto(['Spacrcan', mRNA, is]), verbo([expressed]), complemento([in, both, retina, and, pineal, gland, and, was, detectable, as, early, as, embryonic, day, 15])]). relacion([sujeto(['The', protein, is, first, detectable, in, the, 'IPM', at, postnatal, day, 8, where, it]), verbo([increases]), complemento([in, concert, with, the, extension, of, photoreceptor, inner, and, outer, segments, from, the, outer, retinal, surface])]). relacion([sujeto(['The', presence, of, several, unique, regulatory, elements, in, the, promoter, region, and, characteristic, molecular, features, shared, with, the, orthologue, in, human, and, rat]), verbo([suggest]), complemento([an, important, functional, role, of, 'SPACRCAN', in, the, 'IPM'])]). relacion([sujeto(['The', time, of, appearance, of, the, 'SPACRCAN', protein, during, retinal, development]), verbo([suggests]), complemento([that, this, matrix, protein, may, establish, the, extracellular, microenvironment, into, which, photoreceptor, outer, segments, are, elaborated])]). relacion([sujeto(['Atopy']), verbo([has]), complemento([been, linked, to, chromosome, 11, 'q22,', a, region, that, harbors, the, 'IL18', gene])]). relacion([sujeto(['IL-18']), verbo([enhances]), complemento(['IL-4/IL-13', production, and, induces, 'IgE', production, that, is, directly, associated, with, the, pathogenesis, of, atopic, disorders])]). relacion([sujeto(['We']), verbo([have]), complemento([identified, 5, novel, 'SNPs', in, the, 'IL18', gene, '(', -, 920, '[', 't/c],', -, 133, '[', 'c/g],', and, -, 132, '[', 'a/g]', in, promoter, 2, '[', upstream, of, exon, 2, ']', ;, +, 179, '[', 'c/a;', 'Ser35Ser]', in, exon, 4, ;, and, +, 486, '[', 'c/t;', 'Phe137Phe]', in, exon, 6, ')'])]). relacion([sujeto(['Three', 'SNPs', are, located, in, promoter, 2, ',', and, one, '(', -, 133, '[', 'c/g];']), verbo([nuclear]), complemento([factor, 1, 'site)', was, significantly, associated, with, high, serum, 'IgE', levels, '(', 'P', =])]). relacion([sujeto(['In', 'addition,', previously, identified, 'SNPs', in, exon, 1, '(', +, 113, '[', 't/g]', and, +, 127, '[', 'c/t])', and, in, promoter, 1, '(', -, 137, '[', 'g/c],', 'GATA3', 'site)', of, the, 'IL18', gene, were, significantly]), verbo([associated]), complemento([with, high, 'IgE', levels, '(', 'P', &, 'lt;', or, =])]). relacion([sujeto(['IL18', might, be, responsible, for, the, linkage, effects, seen, in, the, chromosomal, region, 11, 'q22,', which]), verbo([has]), complemento([been, found, previously, with, the, phenotype, &, 'quot;sensitization', to, mite, allergen])]). relacion([sujeto([&, 'quot;', 'Thus', a, suspected, direct, role, of, 'IL18', in, the, pathogenesis, of, atopy]), verbo([has]), complemento([been, strengthened, by, the, presence, of, 8, common, 'SNPs', in, the, promoter, regions, of, 'IL18'])]). relacion([sujeto(['Here', we]), verbo([have]), complemento([generated, mice, deficient, for, signal, transducer, and, activator, of, transcription, 6, '(', 'STAT6)', and, 'CTLA-4', to, determine, the, role, of, 'CTLA-4', in, 'cytokine-driven', 'T', cell, differentiation])]). relacion([sujeto(['CTLA-4', deficiency, also, affects, the, balance, of, the]), verbo([nuclear]), complemento([factors, 'NFATc1', and, 'NFATc2,', and, enhances, activation, of, 'NF-kappaB'])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, 'CTLA-4', has, a, critical, role, in, 'T', cell, differentiation, and, that, 'STAT6-dependent', 'T(H)2', lineage, commitment, and, stabilization, can, be, bypassed, by, increasing, the, strength, of, signaling, through, the, 'T', cell, receptor])]). relacion([sujeto(['Therefore,', the, 5, '\'', -, flanking, region, of, human, 'pax-5', exon, 1, 'B', could, be]), verbo([involved]), complemento([in, regulating, the, expression, of, human, 'pax-5', and, 'B-cell', differentiation, and, development])]). relacion([sujeto(['The', signal, transducer, and, activator, of, transcription, '(', 'STAT)1', is, a, 'cytoplasmic-transcription', factor, that, is]), verbo([phosphorylated]), complemento([by, 'Janus', kinases, '(', 'Jak)', in, response, to, interferon, 'gamma(IFN-gamma)'])]). relacion([sujeto(['The']), verbo([phosphorylated]), complemento(['STAT1', translocates, to, the, 'nucleus,', where, it, turns, on, specific, sets, of, 'IFN-gamma-inducible', 'genes,', such, as, the, interferon, regulatory, factor, '(', 'IRF)-1'])]). relacion([sujeto(['In', 'contrast,', the, mRNA, levels, of, 'IL-5', and, transcription, factor, 'GATA-3', were, slightly]), verbo([induced]), complemento([by, gamma, irradiation, when, compared, to, the, 'non-irradiated', sample])]). relacion([sujeto(['These', results, postulate, that, gamma, irradiation]), verbo([induces]), complemento([the, 'polarized-Th2', response, and, interferes, with, 'STAT1', 'signals,', thereby, causing, the, immunosuppression, of, the, 'Th1', response])]). relacion([sujeto(['Extrinsic', signals, seem, to, be, integrated, into, 'cell-intrinsic', 'programming,', in, what, is, becoming, an, intriguing, story, of]), verbo([regulated]), complemento([development])]). relacion([sujeto(['We']), verbo([found]), complemento([that, in, these, conditions, human, naive, 'T', cells, acquired, stable, histone, hyperacetylation, at, either, the, 'Ifng', or, 'Il4', promoter])]). relacion([sujeto(['However,', hypoacetylation, of, the, nonexpressed, cytokine, gene, did, not]), verbo([lead]), complemento([to, irreversible, silencing, because, most, 'T(H)1', and, 'T(H)2', cells, acetylated, and, expressed, the, alternative, gene, when, stimulated, under, opposite, 'T(H)', conditions])]). relacion([sujeto(['Such', cytokine, flexibility, was, absent, in, a, subset, of, 'T(H)2', cells, that, failed, to, 'up-regulate', 'T-bet', and, to]), verbo([express]), complemento(['interferon-gamma', when, stimulated, under, 'T(H)1', conditions])]). relacion([sujeto(['Thus,', most, human, 'CD4+', 'T', cells]), verbo([retain]), complemento([both, memory, and, flexibility, of, cytokine, gene, expression])]). relacion([sujeto(['We', showed, that, 'GATA-1,', -, 2, and, -, 3, were]), verbo([expressed]), complemento([only, in, haematopoietic, cells, in, the, bone, marrow])]). relacion([sujeto(['RT-PCR', analysis, demonstrated, that, '(', 1, ')', 'GATA-1', expression, significantly]), verbo([increased]), complemento([during, 'gestation;', '(', 2, ')', 'GATA-2', expression, peaked, at, the, onset, of, medullary, 'haematopoiesis,', declined, 'thereafter,', and, remained, at, a, constant, level, after, 30, weeks, post, 'conception;', and, '(', 3, ')', 'GATA-3', expression, revealed, no, changes, during, development])]). relacion([sujeto(['In', this, 'study,', we, show, that, the, 'C-terminal,', but, not, the, 'N-terminal', zinc, finger, '(', 'N-finger)', of, 'GATA-3']), verbo([mediates]), complemento([the, association, with, the, 'IL-4/IL-13', intergenic, 'DNase', 'I', hypersensitive, site, and, the, induction, of, an, extended, 'DNase', 'I', hypersensitivity, on, the, 'IL-4/IL-13', locus])]). relacion([sujeto(['In', 'contrast,', the, 'N-finger', of, 'GATA-3', was, indispensable, for, the]), verbo([binding]), complemento([to, the, 'IL-5', promoter, and, the, induction, of, 'IL-5'])]). relacion([sujeto(['Interleukin', '(', 'IL)-4', is, thought, to, be, 'important,', although, not, strictly, 'necessary,', for, 'Th2', 'differentiation,', although]), verbo([triggers]), complemento([of, 'IL-4-independent', 'Th2', polarization, have, not, been, identified])]). relacion([sujeto(['GATA-3', and, 'CCR3,', -, 4, ',', and, -, 8, were]), verbo([expressed]), complemento([in, the, lymph, nodes, of, 'WT', and, 4, 'KO', mice, at, similar, 'levels,', as, were, 'IL-5', and, 'IL-13', levels, in, the, 'BAL,', 'T1/ST2', on, lung, 'Th', 'cells,', and, 'BAL', eosinophils, after, recall, challenge])]). relacion([sujeto(['We', conclude, that, 'IL-4', is, not]), verbo([required]), complemento([for, the, generation, of, 'Th2-polarized', responses, in, the, presence, of, 'GM-CSF'])]). relacion([sujeto(['Previously,', we]), verbo([have]), complemento([shown, in, a, model, of, hypersensitivity, pneumonitis, that, 'Th1-biased', 'C57BL/6', mice, are, susceptible, and, 'Th2-biased', 'DBA/2', mice, are, resistant, to, disease])]). relacion([sujeto(['For', these, 'reasons,', we, postulated, that, 'C57BL/6', and, 'DBA/2', mice, differentially]), verbo([express]), complemento(['IL-4'])]). relacion([sujeto(['In', this, 'study,', we, show, that, 'C57BL/6', immune, cells]), verbo([express]), complemento(['Th2', but, not, 'Th1', cytokines, at, lower, levels, than, 'DBA/2', cells])]). relacion([sujeto(['We', also]), verbo([found]), complemento([that, 'C57BL/6', splenocytes, exhibit, decreased, mRNA, stability, of, 'Th2', 'cytokines,', relative, to, 'DBA/2', splenocytes])]). relacion([sujeto(['Furthermore,', expression, of, 'Th1-', and, 'Th2-specific', transcription, factors, 'T-bet', and, 'GATA-3,', as, well, as, the]), verbo([nuclear]), complemento([factor, of, activated, 'T', cells, transcription, 'factor,', 'NFATc,', was, not, significantly, different, between, the, two, mice])]). relacion([sujeto(['Our', data]), verbo([suggest]), complemento([that, decreased, mRNA, stability, of, 'Th2', cytokines, in, 'C57BL/6', splenocytes, may, underlie, the, differential, susceptibility, to, hypersensitivity, pneumonitis, between, 'C57BL/6', and, 'DBA/2', mice])]). relacion([sujeto(['This', 'Th2', response]), verbo([has]), complemento([been, thoroughly, documented, by, measuring, the, levels, of, 'Th2', cytokines, produced, by, 'CD4(+)', 'T', cells, present, in, the, lymphoid, organs, by, 'enzyme-linked', immunosorbent, assay, and, 'PCR'])]). relacion([sujeto(['major-specific', 'Th2', cells]), verbo([has]), complemento([never, been, determined])]). relacion([sujeto(['We', analyzed, the, intracellular, cytokine, profile, of, 'CD4(+)', 'T1/ST2(+)', 'T', cells, and, showed, that, they, clearly, displayed, a, 'Th2', 'phenotype,', as, they]), verbo([expressed]), complemento([interleukin, 4, '(', 'IL-4),', 'IL-10,', and, 'IL-5'])]). relacion([sujeto(['In', 'addition,', we, detected, another, population, of, 'Th2', cells, among, the, 'CD4(+)', 'T1/ST2(-)', 'T', cells, that]), verbo([expressed]), complemento(['IL-4', and, 'IL-10', but, excluded, 'IL-5'])]). relacion([sujeto(['major-infected', 'BALB/c', 'mice;', 'Th2', cells, from, both, subsets]), verbo([expressed]), complemento(['IL-4', and, 'IL-10,', but, they, could, be, distinguished, by, their, expression, of, 'IL-5', and, 'T1/ST2'])]). relacion([sujeto(['Members', of, the, 'GATA', transcription, factor, gene, family]), verbo([have]), complemento([been, implicated, in, a, variety, of, developmental, 'processes,', including, that, of, the, vertebrate, central, nervous, system])]). relacion([sujeto(['We', show, that, both, proteins, are]), verbo([expressed]), complemento([by, a, distinct, subpopulation, of, ventral, interneurons, that, share, the, same, dorsoventral, position, as, 'CHX10-positive', 'V2', interneurons])]). relacion([sujeto(['In', 'addition,', we, further, show, that, 'Sonic', hedgehog]), verbo([induces]), complemento(['GATA3', expression, in, a, 'dose-dependent', manner])]). relacion([sujeto(['Using', in, ovo, 'electroporations,', we, also, demonstrate, that, 'GATA2', is, upstream, of, 'GATA3', in, the, same, epigenetic, cascade, and, that, 'GATA3', is, capable, of]), verbo([inducing]), complemento(['GATA2', expression, in, vivo])]). relacion([sujeto(['Furthermore,', the, ectopically]), verbo([expressed]), complemento(['GATA', proteins, can, repress, differentiation, of, other, ventral, cell, 'fates,', but, not, the, development, of, progenitor, populations, identified, by, 'PAX', protein, expression])]). relacion([sujeto(['Taken', 'together,', our, findings, strongly]), verbo([suggest]), complemento([an, important, role, for, 'GATA2', and, 'GATA3', proteins, in, the, establishment, of, a, distinct, ventral, interneuron, subpopulation, in, the, developing, chick, spinal, cord])]). relacion([sujeto(['Hyperacetylation', of, histone, 'H3', on, nucleosomes]), verbo([associated]), complemento([with, the, interleukin, '(', 'IL)-4,', 'IL-13', and, 'IL-5', genes, was, observed, in, developing, 'Th2', cells, but, not, in, 'Th1', cells])]). relacion([sujeto(['A']), verbo([conserved]), complemento(['GATA3', response, element, '(', 'CGRE)', containing, four, 'GATA', consensus, sequences, was, identified, 1.6, kbp, upstream, from, the, 'IL-13', 'gene,', corresponding, with, the, 5, '\'', -, border, of, the, 'Th2-specific', histone, hyperacetylation, region])]). relacion([sujeto(['The', 'CGRE', was, shown, to]), verbo([bind]), complemento([to, 'GATA3,', histone, acetyltransferase, complexes, including, 'CBP/p300,', and, 'RNA', polymerase, 'II'])]). relacion([sujeto(['Also,', the, 'CGRE', showed, a, significant]), verbo([enhancing]), complemento([effect, on, the, 'Th2', cytokine, gene, promoters])]). relacion([sujeto(['Thus,', the, 'CGRE', may, play, a, crucial, role, for, 'GATA3-mediated']), verbo([targeting]), complemento([and, downstream, spreading, of, core, histone, hyperacetylation, within, the, 'IL-13', and, 'IL-4', gene, loci])]). relacion([sujeto(['We']), verbo([have]), complemento([developed, an, in, vitro, differentiation, assay, in, which, human, naive, 'CD4(+)', cells, are, driven, toward, either, the, 'Th1', or, 'Th2', phenotype])]). relacion([sujeto(['We']), verbo([have]), complemento([examined, the, interrelationships, among, the, expression, of, 'IL-2,', 'IL-4,', 'IL-5,', 'IL-10,', 'IL-13,', 'GM-CSF,', and, 'IFN-gamma', in, individual, cells, using, intracellular, cytokine, staining, at, various, times, during, the, differentiation, process])]). relacion([sujeto(['We']), verbo([provide]), complemento([direct, evidence, that, the, 'Th2', cytokines, 'IL-4,', 'IL-5,', and, 'IL-13,', unlike, the, other, 'cytokines,', are, regulated, by, a, coordinated, mechanism])]). relacion([sujeto(['We', also, show, that, 'IL-10', is]), verbo([expressed]), complemento([by, a, different, subset, of, cells, that, is, prevalent, at, early, stages, of, 'Th2', 'differentiation,', but, then, diminishes])]). relacion([sujeto(['Additionally', we, demonstrate, that, while, naive, cells, can]), verbo([express]), complemento(['IL-2', upon, 'activation,', they, cannot, express, 'GM-CSF'])]). relacion([sujeto(['Furthermore,', we]), verbo([have]), complemento([examined, the, levels, of, 'GATA3,', 'c-Maf,', 'T-bet,', and, 'Ets-related', molecule, during, human, 'Th1/Th2', differentiation, and, suggest, that, differences, in, the, levels, of, these, critical, transcription, factors, are, responsible, for, commitment, toward, the, 'Th1', or, 'Th2', lineage])]). relacion([sujeto(['Certain', 'IFN', regulatory, factor, '(', 'IRF)', transcription, factors, indirectly, influence, 'T', helper, '(', 'Th)', cell, differentiation, by]), verbo([regulating]), complemento([the, production, of, 'IL-12'])]). relacion([sujeto(['Here,', we, show, that, 'IRF4', directly]), verbo([regulates]), complemento(['Th', cell, differentiation, in, vitro, and, in, vivo, during, murine, leishmaniasis])]). relacion([sujeto(['In', the, absence, of, 'IRF4,', 'IL-12-induced', 'Th1', cell, differentiation, was, 'compromised,', while, 'IL-4', failed, to]), verbo([induce]), complemento(['Th2', cell, differentiation])]). relacion([sujeto(['Instead,', 'IL-4', tended, to]), verbo([induce]), complemento(['Th1', 'cells,', defined, by, production, of, 'IFN-gamma', and, 'TNF'])]). relacion([sujeto(['Based', on, previous, animal, experiments, that]), verbo([suggest]), complemento([the, plasticity, of, peripheral, 'blood-derived,', 'CD34(-)', stem, cell, 'lines,', the, aim, of, this, study, was, to, isolate, 'CD34(-)', stem, cell, lines, from, human, peripheral, blood, cells, and, obtain, evidence, of, their, multipotency, and, plasticity])]). relacion([sujeto(['The', peripheral, 'blood-derived', and, 'fibroblast-like', cell, line, 'V54/2']), verbo([expressed]), complemento([high, levels, of, 'CD10', and, 'CD105', and, showed, only, a, very, low, level, expression, of, 'CD34', '(', &, 'lt;1'])]). relacion([sujeto(['Among', the, entire, 'CD34(-)CD105(+)', cell, population, that]), verbo([transcribed]), complemento([factors, such, as, 'Myb,', 'Tie-1,', and, 'VEGF,', there, was, a, small, 'Rh123(low)CD34(+)', subpopulation, that, transcribed, significant, levels, of, several, members, of, the, 'GATA', family, of, transcription, factors])]). relacion([sujeto(['The', morphology, of, the, 'Rh123(low)CD34(+)', '(', also]), verbo([expressing]), complemento([the, 'P-glycoprotein)', was, different, compared, to, the, 'Rh123(high)CD34(-)', population])]). relacion([sujeto(['The', findings]), verbo([provide]), complemento([evidence, that, it, is, possible, to, isolate, 'CD34(-)CD105(+)', mesenchymal, stem, cell, lines, from, human, peripheral, blood, cells, that, contain, a, small, subpopulation, of, 'CD34(+)', and, 'GATA-transcribing', cells])]). relacion([sujeto(['Those', cells, are, potential, hematopoietic, progenitors, and, can, be]), verbo([recruited]), complemento([from, the, 'CD34(-)', stem, cell, pool])]). relacion([sujeto(['The', plasticity, of, stem, cells, seems, to]), verbo([require]), complemento([essential, molecular, 'tools,', such, as, a, panel, of, transcription, 'factors,', to, respond, to, the, environmental, demand, within, a, biologic, system])]). relacion([sujeto(['We', examined, cells, lacking, methyl, 'CpG']), verbo([binding]), complemento([domain, 'protein-2', '(', 'MBD2),', a, molecule, that, has, been, proposed, to, link, 'DNA', methylation, to, silent, chromatin])]). relacion([sujeto(['IL-4,', the, signature, of, a, restricted, set, of, 'progeny,', is]), verbo([expressed]), complemento([ectopically, in, 'Mbd2(-/-)', parent, and, daughter, cells])]). relacion([sujeto(['Gata-3', and, 'MBD2']), verbo([act]), complemento([in, 'competition,', wherein, each, factor, 'independently,', and, 'quantitatively,', regulates, the, binary, choice, of, whether, heritable, 'IL-4', expression, is, established])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, activating, and, silencing, signals, integrate, to, provide, spatially, and, temporally, restricted, patterns, of, gene, activity])]). relacion([sujeto(['Many', 'light-responsive', promoters, contain, 'GATA', motifs, and, a, number, of]), verbo([nuclear]), complemento([proteins, have, been, defined, that, interact, with, these, elements])]). relacion([sujeto(['Type-IV', 'zinc-finger', proteins]), verbo([have]), complemento([been, extensively, characterised, in, animals, and, fungi, and, are, referred, to, as, 'GATA', factors, by, virtue, of, their, affinity, for, promoter, elements, containing, this, sequence])]). relacion([sujeto(['Transcripts', from, all, four, genes, can, be, detected, in, all, tissues, examined]), verbo([suggesting]), complemento([that, they, are, not, developmentally, regulated, at, the, level, of, transcription])]). relacion([sujeto(['In', vitro]), verbo([binding]), complemento([experiments, with, 'Escherichia', 'coli-derived', recombinant, proteins, were, performed, using, motifs, previously, defined, as, targets, for, nuclear, 'GATA-binding', proteins])]). relacion([sujeto(['These', studies]), verbo([reveal]), complemento([differences, in, 'DNA', binding, specificity, of, 'GATA-1', as, compared, to, the, other, three, proteins])]). relacion([sujeto(['In', vivo, 'protein-DNA', interactions, monitored, by, yeast, 'one-hybrid', assays]), verbo([reveal]), complemento([different, binding, characteristics, as, compared, to, those, defined, with, 'E'])]). relacion([sujeto(['We', conclude, that, the, 'Arabidopsis', 'type-IV', 'zinc-finger', proteins, may, represent, the, previously, defined, family, of]), verbo([nuclear]), complemento(['GATA-binding', proteins, implicated, in, 'light-responsive', transcription])]). relacion([sujeto(['To', determine, the, role, of, 'GATA-3', '(', a, transcript, factor, that]), verbo([has]), complemento([influences, on, 'Th2', cell, 'differentiation)', in, the, development, of, anterior, chamber, associated, immune, deviation, '(', 'ACAID)'])]). relacion([sujeto(['Immunohistochemistry', and, 'Western', blot, were, used, to, determine, the, localization, and, relative, protein, levels, of, 'GATA-3', respectively, at, different, time, points, after, anterior, chamber, injection, of, 50, microgram, interphotoreceptor, retinoid]), verbo([binding]), complemento([protein, '(', 'IRBP)'])]). relacion([sujeto(['GATA-3', was, detected, weakly, in, normal, spleen, and]), verbo([increased]), complemento([significantly, at, 5, ',', 7, ',', 14, and, 21, days, after, anterior, chamber, inoculation])]). relacion([sujeto(['The', expression, of, 'GATA-3']), verbo([increases]), complemento([earlier, than, development, of, 'ACAID'])]). relacion([sujeto(['It']), verbo([suggests]), complemento([that, 'GATA-3', play, an, important, role, in, 'Th2', commitment, during, 'ACAID', development])]). relacion([sujeto(['Defining', these, transcription, factor, combinations, is, an, important, aspect, of, research, in, developmental, neurobiology, that, promises, to]), verbo([provide]), complemento([incredible, insights, into, the, 'structure,', 'function,', and, pathology, of, the, central, nervous, system])]). relacion([sujeto(['Section', 'RNA', in, situ, hybridisation, revealed, that, 'SCL', is, transiently]), verbo([expressed]), complemento([within, the, 'V2', postmitotic, domain, of, the, developing, mouse, spinal, cord, between, 10.5, and, 13.5, days, post, coitum])]). relacion([sujeto(['These', experiments, revealed, that, 'SCL', is]), verbo([expressed]), complemento([in, a, medially, restricted, subpopulation, of, 'GATA-3', producing, 'cells,', suggesting, a, possible, role, for, this, factor, in, the, differentiation, of, the, 'GATA', population, of, 'V2', interneurons])]). relacion([sujeto(['The', phenotype, is, the, result, of, haploinsufficiency, of, at, least, two, regions, on, 10, 'p,', the, 'HDR1', region]), verbo([associated]), complemento([with, 'hypoparathyroidism,', sensorineural, 'deafness,', and, renal, defects, '(', 'HDR', 'syndrome)', and, the, more, proximal, region, 'DGCR2', responsible, for, heart, defects, and, thymus, 'hypoplasia/aplasia'])]). relacion([sujeto(['While', 'GATA3', was, identified, as, the, disease]), verbo([causing]), complemento([gene, for, 'HDR', 'syndrome,', no, genes, have, been, identified, thus, far, for, the, symptoms, associated, with, 'DGCR2', haploinsufficiency])]). relacion([sujeto(['We', did, not]), verbo([find]), complemento(['BRUNOL3', mutations, in, 92, 'DiGeorge', 'syndrome-like', patients, without, chromosomal, deletions, and, in, 8, parents, with, congenital, heart, defect, children])]). relacion([sujeto(['Over', the, past, 'year,', vertebrate, 'GATA', factors]), verbo([have]), complemento([been, found, to, participate, directly, in, several, 'signal-transduction', pathways])]). relacion([sujeto(['Smad3,']), verbo([phosphorylated]), complemento([by, 'TGF-beta', 'signalling,', interacts, with, 'GATA3', to, induce, differentiation, of, 'T', helper, cells])]). relacion([sujeto(['Hypertrophic', stimuli]), verbo([act]), complemento([through, 'RhoA', 'GTPase', and, 'ROCK', kinase, to, activate, 'GATA4', in, cardiac, myocytes])]). relacion([sujeto(['In', the, 'liver,', 'GATA4', is, elevated, by, 'BMP', and, 'FGF', 'signalling,', and, is, able, to]), verbo([bind]), complemento([to, chromatin, targets])]). relacion([sujeto(['Using', chromatin, immunoprecipitation, we, demonstrate, that, profound]), verbo([increases]), complemento([in, histone, acetylation, occur, at, the, 'IFN-gamma', and, 'IL-4', loci, during, 'Th1/Th2', differentiation])]). relacion([sujeto(['These', changes, in, histone, acetylation, status, are, locus, and, lineage, 'specific,', and, are]), verbo([maintained]), complemento([by, the, transcription, factors, 'Tbet', and, 'GATA3', in, a, 'STAT-dependent', manner])]). relacion([sujeto(['Our', results]), verbo([suggest]), complemento([a, model, of, cytokine, locus, activation, in, which, 'TCR', signals, initiate, chromatin, remodeling, and, locus, opening, in, a, 'cytokine-independent', fashion])]). relacion([sujeto(['Subsequently,', cytokine, signaling, reinforces, polarization, by, expanding, and]), verbo([maintaining]), complemento([the, accessible, state, at, the, relevant, cytokine, locus, '(', 'IL-4', or, 'IFN-gamma)'])]). relacion([sujeto(['We']), verbo([have]), complemento([used, 'Affymetrix', 'high-density', gene, arrays, to, generate, a, temporal, profile, of, gene, expression, during, differentiation, of, 'UB/OC-1,', a, conditionally, immortal, cell, line, derived, from, the, mouse, cochlea])]). relacion([sujeto(['The', results]), verbo([suggest]), complemento([that, 'UB/OC-1', is, derived, from, a, population, of, nonsensory, epithelial, cells, in, the, greater, epithelial, ridge, that, have, the, potential, to, differentiate, into, a, 'hair-cell-like', 'phenotype,', without, the, intervention, of, 'Math1'])]). relacion([sujeto(['Elements', of, the, 'Notch', signaling, cascade, were, 'identified,', including, the, receptor, 'Notch3,', with, a, transient, 'up-regulation', that]), verbo([suggests]), complemento([a, role, in, hair, cell, differentiation])]). relacion([sujeto(['UB/OC-1', also]), verbo([expressed]), complemento(['Me1,', a, putative, partner, of, 'Math1', that, may, confer, competence, to, differentiate, into, hair, cells])]). relacion([sujeto(['Cluster', analysis, revealed, expression, profiles, for, neural, guidance, genes]), verbo([associated]), complemento([with, 'Gata3'])]). relacion([sujeto(['The', temporal, dimension, of, this, analysis]), verbo([provides]), complemento([a, powerful, tool, to, study, genetic, mechanisms, that, underlie, the, conversion, of, nonsensory, epithelial, cells, into, hair, cells])]). relacion([sujeto(['Immunological', memory]), verbo([involves]), complemento([the, fast, recall, of, cytokine, expression, by, 'T', helper, '(', 'Th)', lymphocytes])]). relacion([sujeto(['Two', distinct, profiles, of, cytokine, 'expression,', 'Th1', and, 'Th2,', can, be]), verbo([induced]), complemento([by, antigen, and, polarizing, signals, during, activation, of, naive, 'Th', cells, and, can, subsequently, be, reexpressed, on, stimulation, by, antigen, alone])]). relacion([sujeto(['The', transcription, factor, 'GATA-3']), verbo([induces]), complemento(['Th2', development])]). relacion([sujeto(['GATA-3', is]), verbo([activated]), complemento([by, the, 'Th2-polarizing', 'stimulus,', 'IL-4,', and, has, recently, been, observed, to, autoactivate, its, transcription])]). relacion([sujeto(['Suprathreshold', 'IL-4', signals]), verbo([induce]), complemento([a, transition, from, basal, to, high, 'GATA-3', expression])]). relacion([sujeto(['While', in, primary, activations, differential, expression, of, cytokine, genes, is, dependent, on, 'antigen-receptor', signaling, and, differentiation, 'signals,', in, later, activations, the, expression, is]), verbo([triggered]), complemento([by, 'antigen-receptor', signaling, and, dependent, on, the, cytokine, memory])]). relacion([sujeto(['GATA-3', for, 'Th2', and, 'T-bet', for, 'Th1', cells]), verbo([expressing]), complemento(['interleukin-4', or, 'interferon-gamma,', 'respectively,', are, prime, candidates, for, key, transcription, factors, of, cytokine, memory])]). relacion([sujeto(['The', essential, role, of, epigenetic, modifications, is]), verbo([suggested]), complemento([by, the, requirement, of, 'DNA', synthesis, for, the, establishment, of, a, cytokine, memory, in, 'Th', lymphocytes])]). relacion([sujeto(['The', initial, cytokine, memory, is, not, stable, against, adverse, differentiation, 'signals,', while, in, repeatedly]), verbo([stimulated]), complemento([lymphocytes, it, is, stabilized, by, a, variety, of, mechanisms])]). relacion([sujeto(['In', this, 'study,', we]), verbo([report]), complemento([the, identification, of, a, regulatory, region, located, within, the, first, intron, of, the, murine, 'GATA-3', gene])]). relacion([sujeto(['By', using, yeast, 'one-hybrid', 'screening,', we, discovered, that, fetal, liver, zinc, finger, protein, 1, '(', 'Fliz1)', could]), verbo([bind]), complemento([specifically, to, the, negative, 'cis-acting', 'element,', the, sequence, of, which, is, conserved, between, the, mouse, and, human, 'GATA-3', genes])]). relacion([sujeto(['Our', data]), verbo([suggest]), complemento([that, the, expression, of, 'GATA-3', might, be, partly, regulated, by, the, intronic, regulatory, region, and, 'Fliz1', in, a, developmental, 'stage-specific', fashion])]). relacion([sujeto(['To', identify, cellular, genes, that, may, be]), verbo([involved]), complemento([in, human, papillomavirus, '(', 'HPV)-mediated', immortalization, mRNA, differential, display, analysis, was, performed, on, preimmortal, and, subsequent, immortal, stages, of, four, human, keratinocyte, cell, lines, transformed, by, 'HPV', type, 16, or, 18, 'DNA'])]). relacion([sujeto(['Immunohistochemical', analysis, of, cervical, tissue, specimens, showed, a, clear]), verbo([nuclear]), complemento([staining, for, 'GATA-3', in, normal, cervical, squamous, epithelium, '(', n, =, 14, ')', and, all, cervical, intraepithelial, neoplasia, '(', 'CIN)', 'I', '(', n, =, 6, ')', and, 'CIN', 'II', lesions, '(', n, =, 2, ')'])]). relacion([sujeto(['Whether', 'GATA-3', 'down-regulation', is, etiologically]), verbo([involved]), complemento([in, 'HPV-mediated', immortalization, and, cervical, carcinogenesis, remains, to, be, examined])]). relacion([sujeto(['We']), verbo([found]), complemento([that, continued, culture, in, the, presence, of, polarizing, cytokines, established, a, selective, pattern, of, histone, acetylation, on, both, cytokine, 'genes;', this, correlated, with, restricted, access, of, the, transcription, factor, 'NFAT1', to, these, gene, regulatory, regions, as, well, as, mutually, exclusive, gene, expression, by, the, differentiated, 'T', cells])]). relacion([sujeto(['Our', data, point, to, a, biphasic, process, in, which, 'cytokine-driven', signaling, pathways]), verbo([maintain]), complemento([and, reinforce, chromatin, structural, changes, initiated, by, the, 'TCR'])]). relacion([sujeto(['This', process]), verbo([ensures]), complemento([that, cytokine, genes, remain, accessible, to, the, relevant, transcription, factors, and, promotes, functional, cooperation, of, the, inducible, transcription, factor, 'NFAT', with, 'lineage-specific', transcription, factors, such, as, 'GATA-3', and, 'T-bet'])]). relacion([sujeto(['Although', 'Gata3', is, critical, for, 'Th2', 'polarization,', it, is, not, sufficient, to]), verbo([mediate]), complemento(['IL-4-driven', cell, expansion])]). relacion([sujeto(['We']), verbo([report]), complemento([that, growth, factor, 'independent-1', '(', 'Gfi-1),', a, 'Stat6-dependent', transcriptional, 'repressor,', strikingly, increases, 'Th2', cell, expansion, by, promoting, proliferation, and, preventing, apoptosis])]). relacion([sujeto(['Cells', infected, with, a, 'Gfi-1', retrovirus, show, striking, enhancement, of, 'IL-2-induced', 'Stat5', phosphorylation, and, repression, of, 'p27(Kip-1)', 'expression,']), verbo([suggesting]), complemento([a, potential, mechanism, for, the, 'Gfi-1', growth, effect])]). relacion([sujeto(['The', synergy, of, 'Gfi-1', and, 'Gata3']), verbo([provides]), complemento([a, mechanism, through, which, 'IL-4', could, selectively, promote, 'Th2', cell, expansion])]). relacion([sujeto(['The', promoter, and, enhancer, elements, of, the, mouse, erythropoietin, '(', 'mEpo)', 'gene,', which]), verbo([have]), complemento([high, homology, with, those, of, the, human, erythropoietin, '(', 'hEpo)', 'gene,', were, fused, with, luciferase])]). relacion([sujeto(['The', wild, type, '(', 'TGATA)', showed, a, 39.5, -, fold]), verbo([increase]), complemento([in, induction, by, hypoxia])]). relacion([sujeto(['Mouse', 'GATA-2']), verbo([inhibited]), complemento([the, hypoxic, induction, of, the, 'wild-type', '(', 'm3),', promoterluciferase, construct, but, not, the, hypoxic, induction, of, the, mutant, '(', 'm4,', 5, ')', 'promoter-luciferase', constructs])]). relacion([sujeto(['N(G)-monomethyl', 'L-arginine', '(', 'L-NMMA)']), verbo([inhibited]), complemento([the, hypoxic, induction, of, the, m3, 'promoter-luciferase', 'construct,', but, this, inhibition, was, recovered, by, 'L-arginine'])]). relacion([sujeto(['H2O2', also]), verbo([inhibited]), complemento([the, hypoxic, induction, of, the, m3, 'promoter-luciferase', 'construct,', but, this, inhibition, was, recovered, by, catalase])]). relacion([sujeto(['Gel', shift, assays, performed, on]), verbo([nuclear]), complemento([extracts, of, 293, cells, overexpressing, 'mGATA-1,', -, 2, ',', and, -, 3, revealed, that, 'mGATA-1,', -, 2, ',', and, -, 3, bind, to, the, 'TGATA', element, of, the, mEpo, promoter])]). relacion([sujeto(['These', results, indicate, that, mGATA]), verbo([binds]), complemento([to, the, 'TGATA', site, of, the, mEpo, promoter, and, negatively, regulates, mEpo, gene, expression])]). relacion([sujeto(['Pathogenic', infections]), verbo([lead]), complemento([to, activation, of, innate, immunity, followed, by, induction, of, a, type, 1, 'T', cell, subset, 'and,', 'therefore,', provide, a, good, model, to, evaluate, when, 'T', cells, commit, to, type, 1, 'T', cells])]). relacion([sujeto(['The', first, step, is]), verbo([mediated]), complemento([by, the, basal, function, of, 'macrophage/dendritic', cells, and, is, antigen, independent])]). relacion([sujeto(['This', step]), verbo([modulates]), complemento([the, committed, precursor, frequency, of, 'T', cell, subsets, and, influences, the, expression, of, 'T-box', expressed, in, 'T', cells, '(', 'T-bet)', and, 'GATA-3', genes])]). relacion([sujeto(['IL-12', and, 'NK', cells, are, not]), verbo([required]), complemento([for, this, step])]). relacion([sujeto(['The', second, step]), verbo([requires]), complemento([antigenic, stimulation, of, 'T', cells, together, with, 'IL-12', or, 'IL-4,', and, influences, on, the, expression, of, 'T-bet', and, 'GATA-3'])]). relacion([sujeto([1, and, 'GATA-3', are, transcription, factors, that, are]), verbo([required]), complemento([for, development, of, 'T', cell, progenitors, from, the, earliest, stages])]). relacion([sujeto(['When']), verbo([expressed]), complemento([at, elevated, levels, at, early, stages, of, 'T', cell, 'development,', each, of, these, transcription, factors, blocks, 'T', cell, development, within, a, 'different,', characteristic, time, 'window,', with, 'GATA-3', overexpression, initially, inhibiting, at, an, earlier, stage, than, 'PU'])]). relacion([sujeto(['These', perturbations, are, each]), verbo([associated]), complemento([with, a, distinct, spectrum, of, changes, in, the, regulation, of, genes, needed, for, 'T', cell, development])]). relacion([sujeto(['A', 'first-draft', assembly, of, the, regulatory]), verbo([targets]), complemento([of, these, two, factors, is, presented, as, a, provisional, gene, network])]). relacion([sujeto(['The']), verbo([target]), complemento([genes, identified, here, provide, insight, into, the, basis, of, the, effects, of, 'GATA-3', or, 'PU'])]). relacion([sujeto(['Recent', evidence]), verbo([suggests]), complemento([that, these, factors, may, affect, airway, immunopathology, in, asthma])]). relacion([sujeto(['However,', the, relative, importance, of, individual, cytokines, is, 'unclear,', and, overall, disease, pathogenesis, appears, to]), verbo([involve]), complemento([the, coordinate, activities, of, a, range, of, 'Th2', cytokines, acting, in, sequence, or, in, parallel])]). relacion([sujeto(['PBMC', from, house, dust, mite, '(', 'HDM)-atopic', and, 'non-atopics', were]), verbo([stimulated]), complemento([in, vitro, with, allergen, or, 'anti-CD3/IL-2'])]). relacion([sujeto(['These', findings, identify, 'Th2-associated', 'TFs', as, key, determinants, of, the, atopic, 'phenotype,']), verbo([suggesting]), complemento([their, unique, potential, as, therapeutic, targets, for, disease, control])]). relacion([sujeto(['To', do, 'so,', it]), verbo([has]), complemento([evolved, into, two, specialized, subsets, that, direct, type, 1, and, type, 2, immunity])]). relacion([sujeto(['Because', 'CD81', is]), verbo([expressed]), complemento([on, both, activated, 'T', and, on, 'B', 'cells,', we, examined, the, role, of, 'CD81', expression, by, each, cell, type])]). relacion([sujeto(['CD81-/-', 'TCR', 'Tg', 'T', cells, were, impaired, in, 'IL-4', production, compared, to, 'CD81+/+', 'TCR', 'Tg', 'T', 'cells,', whereas, 'CD81-/-', and, 'CD81+/+', 'BCR', 'Tg', 'B', cells]), verbo([induced]), complemento([equivalent, amounts, of, 'IL-4', in, 'CD81+/+', 'TCR', 'Tg', 'T', cells])]). relacion([sujeto(['CD81-/-', 'TCR', 'Tg', 'T', cells]), verbo([expressed]), complemento([reduced, levels, of, 'ICOS,', 'GATA-3,', 'STAT6', and, phosphorylated, 'STAT6', when, activated, by, 'antigen-presenting', 'B', cells])]). relacion([sujeto(['Taken', 'together,', these, results, indicate, that, 'CD81', expression, by, 'T', cells, greatly]), verbo([enhances]), complemento([cognate, 'T-B', cell, interactions, and, greatly, augments, intracellular, activation, pathways, leading, to, 'Th2', polarization])]). relacion([sujeto(['Recent', studies, raise, the, possibility, that, 'T', helper, '(', 'Th)', polarization, may, be, attributable, to, generalized, activation, and]), verbo([regulated]), complemento([silencing, rather, than, regulated, activation, of, target, cytokine, genes])]). relacion([sujeto(['The']), verbo([binding]), complemento([of, transcription, factors, 'GATA-3', or, 'T-bet', to, specific, enhancers, does, recruit, transcription, factors, such, as, 'NFAT-1', to, 'IL-4', or, 'IFNgamma', 'promoters,', 'respectively;', 'however,', 'GATA-3', also, intrinsically, suppresses, 'T-bet', and, vice, versa])]). relacion([sujeto(['Silencing', of, 'GATA-3/T-bet,', which, is, influenced, by, factors, such, as, 'cytokines,', is]), verbo([associated]), complemento([with, irreversible, 'Th', polarization])]). relacion([sujeto(['For', the, first, few, divisions, '(', perhaps, reflecting, the, situation, in, lymph, 'nodes),', naive, 'Th', cells]), verbo([retain]), complemento(['pluripotency;', after, further, cell, divisions, '(', perhaps, under, the, influence, of, an, inflammatory, cytokine, 'milieu)', they, may, become, polarized, appropriately, to, respond, to, the, specific, environment])]). relacion([sujeto(['The', commitment, of, naive, 'T', cells, to, polarized, 'Th', cells]), verbo([requires]), complemento([specific, changes, in, their, transcription, factors])]). relacion([sujeto(['Retrovirally', overexpressed, 'GATA-3']), verbo([has]), complemento([been, reported, to, induce, the, 'Th2', cytokine, profile, in, developing, 'Th1', cells])]). relacion([sujeto(['Naive', 'T', cells]), verbo([express]), complemento([significant, levels, of, 'FOG', 'mRNA,', which, was, rapidly, 'down-regulated', upon, commitment, to, both, 'Th1', and, 'Th2', lineages])]). relacion([sujeto(['Finally,', retroviral, expression, of, 'FOG', in, developing, 'Th2', cells]), verbo([suppressed]), complemento([both, 'IL-4', and, 'IL-5', and, allowed, for, 'IFN-gamma', 'production,', which, was, accompanied, by, a, significant, level, of, 'T-bet', mRNA, expression])]). relacion([sujeto(['Serial', deletion, mutation, analysis, indicated, that, the, 'N-terminal', 'region,', but, not, the, consensus, 'C-terminal']), verbo([binding]), complemento(['protein-binding', 'motif,', of, 'FOG', is, critical, for, the, effects])]). relacion([sujeto(['Our', results, clearly, indicate, that, 1, ')', 'FOG', is, a, repressor, of, 'GATA-3', in, naive, 'T', cells, and, 2, ')', the, 'down-regulation', of, 'FOG']), verbo([induces]), complemento(['Th2', cell, differentiation, by, releasing, 'GATA-3', from, its, repression])]). relacion([sujeto(['The', 'GATA', family, of, transcription, factors]), verbo([regulates]), complemento([development, of, multiple, tissues])]). relacion([sujeto(['Several', 'GATA', factors]), verbo([have]), complemento([two, promoters, directing, distinct, 'tissue-specific', expression])]). relacion([sujeto(['Although', 'GATA-3']), verbo([acts]), complemento([in, both, neuronal, and, thymocyte, 'development,', no, alternative, promoter, usage, has, been, reported])]). relacion([sujeto(['We', examined, various, cell, types, and, tissues, for, potential, alternative, 'GATA-3', transcripts, and, identified, an, alternative, transcript, directed, by, a, promoter, located, 10, kb, upstream, of, the]), verbo([recognized]), complemento([promoter])]). relacion([sujeto(['Sequences', within, this, promoter, and, alternative, first, exon, are, highly]), verbo([conserved]), complemento([between, mouse, and, human, genomes])]). relacion([sujeto(['This', new, promoter, is]), verbo([expressed]), complemento([selectively, in, the, brain, but, is, essentially, undetectable, in, the, thymus])]). relacion([sujeto(['In', 'contrast,', the]), verbo([recognized]), complemento([promoter, is, selectively, expressed, in, the, thymus, but, not, in, the, brain])]). relacion([sujeto(['We', also, observed, a, gradual]), verbo([increase]), complemento([in, expression, from, this, new, promoter, during, 'Th2', development])]). relacion([sujeto(['Asthma', 'therapy,', like, other, 'therapies,']), verbo([has]), complemento([been, moving, towards, a, molecular, basis, for, several, years])]). relacion([sujeto(['This', 'year,', there]), verbo([have]), complemento([been, several, preclinical, studies, published, which, utilize, attributes, or, facets, of, 'DNA', to, address, asthma, therapeutics])]). relacion([sujeto(['These', include, antisense, oligonucleotides, '(', against, the]), verbo([nuclear]), complemento([transcription, factor, 'GATA-3', and, the, mast, cell, chemotactic, 'agent,', stem, cell, 'factor),', gene, transfer, '(', of, 'interleukin-18,', both, by, plasmid, and, viral, 'vectors),', and, 'CpG', oligodeoxynucleotides, '(', which, suppress, 'Th2', and, stimulate, 'Th1', 'responses)'])]). relacion([sujeto(['No', clinical, experience]), verbo([has]), complemento([yet, been, reported, for, any, of, these, areas, of, research, in, 'asthma,', but, clinical, trials, are, ongoing, utilizing, 'CpG', oligonucleotides])]). relacion([sujeto(['To', locate, elements]), verbo([regulating]), complemento([the, human, 'CD8', gene, 'complex,', we, mapped, nuclear, matrix, attachment, regions, '(', 'MARs)', and, 'DNase', 'I', hypersensitive, '(', 'HS)', sites, over, a, 100, -, kb, region, that, included, the, 'CD8B', 'gene,', the, intergenic, 'region,', and, the, 'CD8A', gene])]). relacion([sujeto(['MARs', facilitate, 'long-range', chromatin, remodeling]), verbo([required]), complemento([for, enhancer, activity, and, have, been, found, closely, linked, to, several, lymphoid, enhancers])]). relacion([sujeto(['To', further, establish, the, importance, of, this, 'region,', we, obtained, 19, kb, of, sequence, and, screened, for, potential]), verbo([binding]), complemento([sites, for, the, 'MAR-binding', 'protein,', 'SATB1,', and, for, 'GATA-3,', both, of, which, are, critical, for, 'T', cell, development])]). relacion([sujeto(['By', gel, shift, analysis, we, identified, two, strong, 'SATB1']), verbo([binding]), complemento(['sites,', located, 4.5, kb, 'apart,', in, strong, 'MARs'])]). relacion([sujeto(['We', also, detected, strong, 'GATA-3']), verbo([binding]), complemento([to, an, oligonucleotide, containing, two, 'GATA-3', motifs, located, at, an, 'HS', site, in, cluster, 'IV'])]). relacion([sujeto(['This', clustering, of, 'DNase', 'HS', sites, and, 'MARs', capable, of]), verbo([binding]), complemento(['SATB1', and, 'GATA-3', at, the, 3, '\'', end, of, the, 'CD8B', gene, suggests, that, this, region, is, an, epigenetic, regulator, of, 'CD8', expression])]). relacion([sujeto(['These', two, subsets, produce, distinct, profiles, of, cytokines, and]), verbo([regulate]), complemento([different, immune, responses])]). relacion([sujeto(['Here', we, discuss, transcription, factors, and, signaling, pathways, that, are, selectively]), verbo([expressed]), complemento([or, activated, in, 'Th1', and, 'Th2', cells, to, regulate, cytokine, gene, 'expression,', cell, proliferation, and, apoptosis])]). relacion([sujeto(['CD30', ligand, '(', 'CD30L),', but, not, its, cognate, receptor, 'CD30,', is, frequently]), verbo([expressed]), complemento([on, acute, myeloid, leukaemia, '(', 'AML)', blasts])]). relacion([sujeto(['In', the, present, 'study,', we]), verbo([found]), complemento([that, leukaemic, blasts, presenting, surface, 'CD30L', displayed, a, characteristic, 'cytokine-receptor', pattern, that, makes, them, ideal, targets, for, those, cytokines, usually, produced, by, 'Th2-type', cell, subsets])]). relacion([sujeto(['Furthermore,', a, number, of, 'Th2-associated', 'markers,', including, 'CD30,', 'IL-4', and, 'GATA-3,', were]), verbo([expressed]), complemento([by, residual, 'T', cells, derived, from, 'CD30L+', 'AML', but, not, from, 'CD30L-', 'AML,', in, which, the, presence, of, the, 'Th1-associated', marker, 'LAG-3', was, documented, in, some, cases])]). relacion([sujeto(['The', notion, that, 'IL-4', was, able, to]), verbo([enhance]), complemento([in, vitro, proliferation, of, 'CD30L+/IL-4R+', purified, leukaemic, blasts, suggests, that, the, selective, interaction, of, 'IL-4-producing', 'CD30+', 'T', cells, with, 'CD30L+', leukaemic, progenitors, may, have, a, role, in, the, progression, of, this, particular, 'AML', subset])]). relacion([sujeto(['Human', embryonic, stem, cells]), verbo([have]), complemento([the, potential, to, differentiate, into, various, cell, types, 'and,', 'thus,', may, be, useful, as, a, source, of, cells, for, transplantation, or, tissue, engineering])]). relacion([sujeto(['The', cells]), verbo([express]), complemento([endothelial, cell, markers, in, a, pattern, similar, to, human, umbilical, vein, endothelial, 'cells,', their, junctions, are, correctly, 'organized,', and, they, have, high, metabolism, of, acetylated, 'low-density', lipoprotein])]). relacion([sujeto(['With', further, 'studies,', these, cells, could]), verbo([provide]), complemento([a, source, of, human, endothelial, cells, that, could, be, beneficial, for, potential, applications, such, as, engineering, new, blood, 'vessels,', endothelial, cell, transplantation, into, the, heart, for, myocardial, 'regeneration,', and, induction, of, angiogenesis, for, treatment, of, regional, ischemia])]). relacion([sujeto(['As', previously, 'shown,', enforced, 'GATA-3', expression, in, transgenic, mice]), verbo([inhibits]), complemento(['Th1', differentiation, of, 'CD4', 'T', 'cells,', but, 'unexpectedly,', both, type, 1, '(', interferon, 'gamma)', and, type, 2, '(', interleukin, '(', 'IL)-4', and, 'IL-13)', cytokine, genes, were, activated, in, the, transgenic, 'CD8', 'T', cells])]). relacion([sujeto(['Because', 'IL-13', gene, expression, was, highly]), verbo([enhanced]), complemento([in, vivo, by, 'GATA-3', 'expression,', we, studied, the, human, and, the, mouse, 'IL-13', gene, promoters, and, found, an, 'evolutionary-conserved', association, of, a, consensus, 'GATA', binding, site, and, two, 'GATG', motifs])]). relacion([sujeto(['We', showed, that, efficient, 'GATA-3']), verbo([binding]), complemento([to, this, regulatory, sequence, required, these, three, motifs, and, that, the, affinity, of, the, 'GATA', zinc, fingers, for, this, association, was, five, times, higher, than, for, the, consensus, 'GATA', binding, site, alone])]). relacion([sujeto(['Transfections', in, a, 'T', cell, line, or, transactivation, by, 'GATA-3', showed, that, the, combination, of, the, three, sites, was]), verbo([required]), complemento([for, full, transcriptional, activity, of, the, 'IL-13', gene, promoter])]). relacion([sujeto(['Finally', we, showed, that, this, association, of]), verbo([binding]), complemento([sites, causes, a, very, high, sensitivity, of, the, 'IL-13', gene, promoter, to, small, variations, in, the, level, of, 'GATA-3', protein])]). relacion([sujeto(['Altogether,', these, results, indicate, an, important, role, of, 'GATA-3', in, 'CD8', cytokine, gene, expression, and, demonstrate, that, a, critical, network, of, 'GATA']), verbo([binding]), complemento([sites, highly, modulates, 'GATA-3', activity])]). relacion([sujeto(['The', development, of, the, immune, system, and, the, host, response, to, microbial, infection, rely, on, the, activation, and, silencing, of, 'numerous,', differentially]), verbo([expressed]), complemento([genes])]). relacion([sujeto(['Since', the, 'mid-1980s,', a, primary, goal]), verbo([has]), complemento([been, to, identify, transcription, factors, that, regulate, specific, genes, and, specific, immunological, processes])]). relacion([sujeto(['More', 'recently,', there]), verbo([has]), complemento([been, a, growing, appreciation, of, the, role, of, chromatin, structure, in, gene, regulation])]). relacion([sujeto(['Before', most, activators, of, a, gene, access, their]), verbo([binding]), complemento(['sites,', a, transition, from, a, condensed, to, a, decondensed, chromatin, structure, appears, to, take, place])]). relacion([sujeto(['Conversely,', the, acquisition, of, a, more, condensed, chromatin, structure, is, often]), verbo([associated]), complemento([with, gene, silencing])]). relacion([sujeto(['That', 'is,', the, propagation, of, decondensed, chromatin, at, specific, loci, through, 'DNA', replication, and, cell, division, helps, a, cell, remember, which, genes, are]), verbo([expressed]), complemento([constitutively, in, that, cell, type, or, are, poised, for, expression, upon, exposure, to, a, stimulus])]). relacion([sujeto(['The', 'interleukin-4', gene, serves, as, a, primary, model, for, exploring, the, events]), verbo([involved]), complemento([in, the, acquisition, and, heritable, maintenance, of, a, decondensed, chromatin, structure])]). relacion([sujeto(['To', determine, the, basis, for, default, production, of, 'IFN-gamma', by, gammadelta, 'T', 'cells,', we, analyzed, the, transcription, factors, 'T-box']), verbo([expressed]), complemento([in, 'T', cells, '(', 'T-bet)', and, 'GATA-3'])]). relacion([sujeto(['T-bet,', absent, in, naive, 'cells,', was]), verbo([induced]), complemento([upon, 'TCR', 'signaling,', with, 'IFN-gamma', production])]). relacion([sujeto(['T-bet', also]), verbo([regulated]), complemento(['IL-4', 'synthesis,', as, gammadelta, cells, isolated, from, 'T-bet-deficient', mice, displayed, enhanced, 'IL-4', levels, with, reduced, 'IFN-gamma', production])]). relacion([sujeto(['Notably,', 'T-bet', expression, after, 'TCR', signaling, in, gammadelta, cells, was, not, 'down-regulated', by, 'IL-4,', in, conjunction, with, a, higher, ratio, of, 'T-bet:GATA-3', expression, than, that]), verbo([found]), complemento([in, 'CD4(+)', 'T', cells])]). relacion([sujeto(['Indeed,', overexpression, of, 'GATA-3', failed, to]), verbo([inhibit]), complemento(['IFN-gamma', secretion, in, gammadelta, cells, to, the, degree, seen, in, 'CD4(+)', 'T', cells])]). relacion([sujeto(['These', results, indicate, that, 'T-bet']), verbo([enhances]), complemento(['IFN-gamma', secretion, and, suppresses, 'IL-4', secretion, in, gammadelta, 'cells,', and, that, 'GATA-3', fails, to, counterbalance, 'T-bet-mediated', 'IFN-gamma', 'production,', accounting, for, the, default, synthesis, of, 'IFN-gamma', by, these, 'T', lymphocytes])]). relacion([sujeto(['The', transcription, factors, 'GATA3', and, 'Pax2', are]), verbo([expressed]), complemento([throughout, development, of, the, mouse, inner, ear])]). relacion([sujeto(['We']), verbo([have]), complemento([used, antibodies, to, study, their, temporal, and, spatial, expression, patterns, from, embryonic, days, 'E8-E16'])]). relacion([sujeto(['GATA3', is]), verbo([expressed]), complemento([in, the, whole, otic, placode, at, 'E8'])]). relacion([sujeto(['Only', 'Pax2', is]), verbo([expressed]), complemento([in, the, endolymphatic, 'duct,', but, both, factors, are, expressed, in, the, cochlea])]). relacion([sujeto([5, -, 13.5, ',', 'GATA3', is]), verbo([expressed]), complemento([strongly, in, the, 'cochlea,', but, in, the, 'dorsal,', vestibular, region, it, is, downregulated])]). relacion([sujeto(['Pax2', is]), verbo([expressed]), complemento([in, all, sensory, and, some, nonsensory, 'epithelia,', but, within, sensory, epithelia, at, 'E16'])]). relacion([sujeto(['GATA3', is]), verbo([expressed]), complemento([throughout, key, periods, of, cell, 'proliferation,', fate, 'determination,', and, differentiation, and, is, not, specifically, associated, with, any, of, these, processes])]). relacion([sujeto(['GATA3', is, thus]), verbo([expressed]), complemento([in, functionally, distinct, groups, of, cells, that, integrate, to, form, a, complete, sensory, system])]). relacion([sujeto(['The', results]), verbo([suggest]), complemento([that, both, factors, may, be, involved, in, tissue, 'compartmentalisation,', 'morphogenesis,', and, cell, signalling])]). relacion([sujeto(['Allergen-induced', recruitment, of, 'T', lymphocytes, and, eosinophils, to, the, airways, is]), verbo([associated]), complemento([with, increased, expression, of, the, transcription, factor, 'GATA-3'])]). relacion([sujeto(['Intratracheal', ragweed, challenge]), verbo([increased]), complemento([both, the, number, of, 'GATA-3-expressing', cells, in, the, perivascular, and, peribronchial, regions, and, the, amount, of, expression, per, cell])]). relacion([sujeto(['Eosinophils', isolated, from, the, lungs, and]), verbo([stimulated]), complemento([with, phorbol, 12, -, myristate, 13, -, acetate, 'and/or', 'A-23187', released, 'IL-5'])]). relacion([sujeto(['The']), verbo([release]), complemento([was, inhibited, by, actinomycin, 'D,', which, indicates, that, de, novo, synthesis, of, the, cytokine, was, involved])]). relacion([sujeto(['Western', blot, analysis, of, proteins, from, isolated, eosinophils, demonstrated, expression, of, the, p50, subunit, of]), verbo([nuclear]), complemento(['factor-kappaB,', a, transcription, factor, that, is, implicated, in, control, of, 'GATA-3', expression])]). relacion([sujeto(['These', data]), verbo([provide]), complemento([evidence, that, allergen, challenge, increases, 'GATA-3', and, proinflammatory, cytokine, expression, by, pulmonary, 'eosinophils,', which, could, provide, positive, feedback, for, the, inflammatory, response])]). relacion([sujeto(['Whether', 'GATA', factors, also, serve, to, integrate, epigenetic, signals, on]), verbo([target]), complemento([promoters, 'is,', 'however,', unknown])]). relacion([sujeto(['The', transforming, growth, 'factor-beta', '(', 'TGF-beta)', superfamily, is, a, large, group, of, phylogenetically]), verbo([conserved]), complemento([secreted, factors, controlling, cell, 'proliferation,', 'differentiation,', 'migration,', and, survival, in, multiple, tissues])]). relacion([sujeto(['GATA-3,', a, key, regulator, of, 'T', helper, cell, 'development,', was]), verbo([found]), complemento([to, directly, interact, with, 'Smad3,', an, intracellular, signal, transducer, of, 'TGF-beta'])]). relacion([sujeto(['Complex', formation]), verbo([required]), complemento([a, central, region, in, 'GATA-3', and, the, 'N-terminal', domain, of, 'Smad3'])]). relacion([sujeto(['GATA-3']), verbo([mediated]), complemento([recruitment, of, 'Smad3', to, 'GATA', binding, sites, independently, of, 'Smad3', binding, to, 'DNA,', and, the, two, factors, cooperated, synergistically, to, regulate, transcription, from, the, 'IL-5', promoter, in, a, 'TGF-beta-dependent', manner])]). relacion([sujeto(['Treatment', of, 'T', helper, cells, with, 'TGF-beta']), verbo([promoted]), complemento([the, formation, of, an, endogenous, 'Smad3/GATA-3', nuclear, complex, and, stimulated, production, of, the, 'Th2', cytokine, 'IL-10', in, a, 'Smad3-', and, 'GATA-3-dependent', manner])]). relacion([sujeto(['Although', 'Smad', proteins, are, known, to]), verbo([interact]), complemento([with, a, number, of, general, transcription, 'factors,', these, are, insufficient, to, explain, the, 'tissue-specific', biology, of, 'TGF-beta', proteins])]). relacion([sujeto(['Through', its, interaction, with, 'Smad3,', 'GATA-3', is, able, to, integrate, a, genetic, program, of, cell, differentiation, with, an, extracellular, 'signal,']), verbo([providing]), complemento([a, molecular, framework, for, the, effects, of, 'TGF-beta', on, the, development, and, function, of, specific, subsets, of, immune, cells, and, possibly, other, cell, types])]). relacion([sujeto(['Here,', we]), verbo([report]), complemento([a, detailed, investigation, of, some, early, cytological, and, molecular, processes, occurring, in, the, allantoic, 'bud,', which, are, probably, involved, in, the, production, of, angioblasts, and, hemopoietic, cells])]). relacion([sujeto(['We', show, that, the, allantois, undergoes, a, program, characterized, by, the, prominent, expression, of, several, &, 'quot;hemangioblastic"', genes, in, the, mesoderm, accompanied, by, other, gene, patterns, in, the]), verbo([associated]), complemento([endoderm])]). relacion([sujeto(['VEGF-R2,', at, least, from, stage, 'HH17', 'onward,', is]), verbo([expressed]), complemento([and, is, shortly, followed, by, transcription, factors, 'GATA-2,', 'SCL/tal-1,', and, 'GATA-1'])]). relacion([sujeto(['As', far, as, the, endoderm, is, 'concerned,', 'GATA-3', mRNA, is]), verbo([found]), complemento([in, the, region, where, allantois, will, differentiate, before, the, posterior, instestinal, portal, becomes, anatomically, distinct])]). relacion([sujeto(['Shortly', before, the, bud, grows, 'out,', 'GATA-2', was]), verbo([expressed]), complemento([in, the, endoderm, 'and,', at, the, same, 'time,', the, hemangioblastic, program, became, initiated, in, the, mesoderm])]). relacion([sujeto(['Peroxisome', proliferator, activator, receptor, '(', 'PPAR)-binding', protein, '(', 'PBP)', is, an, important, coactivator, for, 'PPARgamma', and, other]), verbo([nuclear]), complemento([receptors])]). relacion([sujeto(['It']), verbo([has]), complemento([been, identified, as, an, integral, component, of, a, multiprotein, thyroid, hormone, 'receptor-associated', 'protein/vitamin', 'D(3)', 'receptor-interacting', 'protein/activator-recruited', cofactor, complexes, required, for, transcriptional, activity])]). relacion([sujeto(['The', primary, functional]), verbo([cause]), complemento([of, embryonic, lethality, at, embryonic, day11])]). relacion([sujeto(['There', was, a, paucity, of, retinal, 'pigment,', defective, lens, 'formation,', excessive, systemic, 'angiogenesis,', a, deficiency, in, the, number, of, 'megakaryocytes,', and, an]), verbo([arrest]), complemento([in, erythrocytic, differentiation])]). relacion([sujeto(['Some', of, these, defects]), verbo([involve]), complemento(['PPARgamma', and, 'retinoid-sensitive', 'sites,', whereas, others, have, not, been, recognized, in, the, 'PPAR-signaling', pathway])]). relacion([sujeto(['Phenotypic', changes, in, four, organ, systems, observed, in, 'PBP', null, mice, overlapped, with, those, in, mice, deficient, in, members, of, 'GATA,', a, family, of, transcription, factors, known, to]), verbo([regulate]), complemento([differentiation, of, 'megakaryocytes,', 'erythrocytes,', and, adipocytes])]). relacion([sujeto(['We', demonstrate, that, 'PBP']), verbo([interacts]), complemento([with, all, five, 'GATA', factors, 'analyzed,', 'GATA-1,', 'GATA-2,', 'GATA-3,', 'GATA-4,', and, 'GATA-6,', and, show, that, the, binding, of, 'GATA-1,', 'GATA-4,', and, 'GATA-6', to, 'PBP', is, not, dependent, on, the, nuclear, receptor, recognition, sequence, motif, 'LXXLL', '(', where, 'L', is, leucine, and, 'X', is, any, amino, 'acid)', in, 'PBP'])]). relacion([sujeto(['Coexpression', of, 'PBP', with, 'GATA-3', markedly]), verbo([enhanced]), complemento([transcriptional, activity, of, 'GATA-3', in, nonhematopoietic, cells])]). relacion([sujeto(['These', observations, identify, the, 'GATA', family, of, transcription, factors, as, a, new]), verbo([interacting]), complemento([partner, of, 'PBP', and, demonstrate, that, 'PBP', is, essential, for, normal, development, of, vital, organ, systems])]). relacion([sujeto(['The', development, of, naive, 'CD4+', 'T', cells, into, a, 'T', helper, '(', 'Th)', 2, subset, capable, of, producing, interleukin, '(', 'IL)-4,', 'IL-5,', and, 'IL-13']), verbo([involves]), complemento([a, signal, transducer, and, activator, of, transcription, '(', 'Stat)6-dependent', induction, of, 'GATA-3', 'expression,', followed, by, 'Stat6-independent', 'GATA-3', autoactivation])]). relacion([sujeto(['The', friend, of, 'GATA', '(', 'FOG)-1', protein]), verbo([regulates]), complemento(['GATA', transcription, factor, activity, in, several, stages, of, hematopoietic, development, including, erythrocyte, and, megakaryocyte, 'differentiation,', but, whether, 'FOG-1', regulates, 'GATA-3', in, 'T', cells, is, uncertain])]). relacion([sujeto(['Also,', 'FOG-1', overexpression, during, primary, activation, of, naive, 'T', cells]), verbo([inhibited]), complemento(['Th2', development, in, 'CD4+', 'T', cells])]). relacion([sujeto(['Thus,', 'FOG-1', may, be, one, factor, capable, of]), verbo([regulating]), complemento([the, 'Th2', development])]). relacion([sujeto(['In', 'addition,', 'Rlk-/-Itk-/-', cells, showed, impaired, 'TCR-induced', repression, of, the, 'TH2-inducing', transcription, factor, 'GATA-3,']), verbo([suggesting]), complemento([a, potential, mechanism, for, 'TH2', development, in, these, hyporesponsive, cells])]). relacion([sujeto(['Thus,', mutations, that, affect, 'Tec', kinases]), verbo([lead]), complemento([to, complex, alterations, in, 'CD4+', 'TH', cell, differentiation])]). relacion([sujeto(['Naïve', 'CD4(+)', helper, 'T', '(', 'T(H))', cells]), verbo([respond]), complemento([to, stimulation, by, terminally, differentiating, into, two, mature, 'classes,', 'T(H)1', 'cells,', which, express, interferon, gamma, '(', 'IFN-gamma),', and, 'T(H)2', 'cells,', which, express, interleukin, 4, '(', 'IL-4)'])]). relacion([sujeto(['The', transcriptional, activators, 'T-bet', and, 'Gata-3']), verbo([mediate]), complemento([commitment, to, the, 'T(H)1', and, 'T(H)2', 'fates,', 'respectively,', including, chromatin, remodeling, of, signature, genes])]). relacion([sujeto(['IL-12', and, 'IL-4', also, play, critical, roles, in, commitment, by]), verbo([promoting]), complemento([transcriptional, silencing, of, 'Gata-3', and, 'T-bet,', respectively])]). relacion([sujeto(['We', now, show, that, both, 'T-bet', and, 'Gata-3', are]), verbo([induced]), complemento([in, a, cell, 'cycle-independent', manner, in, bipotent, progenitor, cells])]). relacion([sujeto(['We']), verbo([found]), complemento([that, cells, that, cannot, cycle, remain, uncommitted, and, bipotent, in, response, to, the, most, polarizing, signals, for, maturation])]). relacion([sujeto(['These', results]), verbo([provide]), complemento([mechanistic, insight, into, a, mammalian, model, of, terminal, differentiation, by, illustrating, that, cell, 'cycle-coupled', epigenetic, 'effects,', as, originally, described, in, 'yeast,', may, represent, an, evolutionarily, conserved, strategy, for, organizing, signaling, and, cell, fate])]). relacion([sujeto([1, 'alpha,25-Dihydroxyvitamin', 'D3', '(', 'vitD3)', is, an, immunoregulatory, hormone, with, beneficial, effects, on, 'Th1']), verbo([mediated]), complemento([autoimmune, diseases])]). relacion([sujeto(['We', demonstrated, that, vitD3, affects, 'Th', cell, polarization, by]), verbo([inhibiting]), complemento(['Th1', '(', 'IFN-gamma', 'production)', and, augmenting, 'Th2', cell, development, '(', 'IL-4,', 'IL-5,', and, 'IL-10', 'production)'])]). relacion([sujeto(['These', effects, were, observed, in, cultures, driven, with, splenic, 'APC', and, 'Ag,', as, well, as, with, 'anti-CD3', and, 'anti-CD28', 'alone,', indicating, that, 'CD4(+)', cells, can, also, be, direct]), verbo([targets]), complemento([for, vitD3])]). relacion([sujeto(['The']), verbo([enhanced]), complemento(['Th2', development, by, vitD3, was, found, in, both, 'BALB/c', and, 'C57BL/6', mice])]). relacion([sujeto(['An']), verbo([increased]), complemento([expression, of, the, 'Th2-specific', transcription, factors, 'GATA-3', and, 'c-maf', correlated, with, the, increased, production, of, 'Th2', cytokines, after, vitD3, treatment])]). relacion([sujeto(['The', 'vitD3-induced', effects, were, largely]), verbo([mediated]), complemento([via, 'IL-4,', because, neutralization, of, 'IL-4', almost, completely, abrogated, the, augmented, 'Th2', cell, development, after, vitD3, treatment])]). relacion([sujeto(['These', findings]), verbo([suggest]), complemento([that, vitD3, acts, directly, on, 'Th', cells, and, 'can,', in, the, absence, of, 'APC,', enhance, the, development, of, a, 'Th2', phenotype, and, augment, the, expression, of, the, transcription, factors, 'c-maf', and, 'GATA-3'])]). relacion([sujeto(['Our', findings]), verbo([suggest]), complemento([that, the, beneficial, effects, of, vitD3, in, autoimmune, diseases, and, transplantation, operate, through, prevention, of, strong, 'Th1', responses, via, the, action, on, the, 'APC,', while, simultaneously, directly, acting, on, the, 'T', cell, to, enhance, 'Th2', cell, development])]). relacion([sujeto(['Moreover,', adult, bone, marrow, stem, cells]), verbo([have]), complemento([a, lower, capacity, to, generate, 'T', cells, compared, with, fetal, 'liver-', and, umbilical, cord, 'blood-derived', progenitors])]). relacion([sujeto(['Therefore,']), verbo([enhancing]), complemento(['thymic-dependent', 'T', cell, generation, might, hold, great, therapeutic, potential])]). relacion([sujeto(['In', this, study, we, examined, the, therapeutic, potential, of, 'GATA-3', to]), verbo([enhance]), complemento(['T', cell, generation, by, overexpressing, 'GATA-3', in, 'T', cell, progenitors, followed, by, fetal, thymic, organ, culture, '(', 'FTOC)'])]). relacion([sujeto(['We', observed, that, early, during, 'FTOC,', there, was, an]), verbo([enhanced]), complemento([differentiation, toward, the, double, positive, stage, of, 'T', cell, development])]). relacion([sujeto(['From', day, 10, of, 'FTOC,', 'however,', overexpression, of, 'GATA-3']), verbo([induced]), complemento([a, severe, reduction, in, thymic, 'cellularity,', which, probably, correlates, with, the, absence, of, a, functional, 'TCR-beta', chain])]). relacion([sujeto(['We', further, show, that, the, frequency, of, apoptosis, was]), verbo([increased]), complemento([in, 'GATA-3-transduced', thymocytes])]). relacion([sujeto(['This', study, shows, that, a, strictly]), verbo([regulated]), complemento([expression, of, 'GATA-3', is, essential, for, normal, 'T', cell, development, and, this, puts, severe, restrictions, on, the, potential, therapeutic, use, of, continuously, overexpressed, 'GATA-3'])]). relacion([sujeto(['IL-13,', a, 'Th2', 'cell-specific', 'cytokine,', is, a, major, effector, molecule]), verbo([mediating]), complemento([several, pathological, features, of, allergic, asthma])]). relacion([sujeto(['The', cell, type, specificity, of, the, minimal, 'IL-13', promoter, is]), verbo([mediated]), complemento([by, a, functionally, critical, 'GATA-3', site, that, binds, endogenous, 'GATA-3', 'proteins,', whereas, the, induction, by, 'PMA/ionomycin', is, mediated, by, distinct, 'cis-acting', elements])]). relacion([sujeto(['Furthermore,', by]), verbo([expressing]), complemento(['GATA-3', in, 'wild-type', and, 'c-maf', transgenic, 'Th1', 'cells,', we, demonstrate, that, the, expression, of, 'IL-13', is, regulated, by, a, mechanism, distinct, from, that, regulating, the, expression, of, 'IL-4,', and, that, the, expression, of, 'Th1', and, 'Th2', cytokine, genes, does, not, have, to, be, mutually, exclusive, in, effector, 'Th', cells])]). relacion([sujeto(['GATA-binding', proteins, are, a, subfamily, of, zinc, finger, transcription, factors, with, six, members, '(', 'GATA-1-6)', that]), verbo([interact]), complemento([with, the, 'GATA', deoxyribonucleic, acid, '(', 'DNA)', sequence])]). relacion([sujeto(['This', sequence, is]), verbo([found]), complemento([in, the, regulatory, regions, of, many, genes, including, those, encoding, 'T-helper', 2, '(', 'Th2)-like', 'cytokines,', 'receptors,', adhesion, molecules, and, 'enzymes,', which, may, be, important, in, the, pathogenesis, of, bronchial, asthma])]). relacion([sujeto(['Using', 'Western', blot, 'analysis,', 'T-cells', from, asthmatic, subjects]), verbo([expressed]), complemento([5, times, the, level, of, 'GATA-3', compared, to, that, in, normals])]). relacion([sujeto(['Confocal', microscopy, indicated, that, 'GATA-3', expression, was, both]), verbo([nuclear]), complemento([and, cytoplasmic])]). relacion([sujeto(['GATA', 'DNA']), verbo([binding]), complemento([complex, containing, 'GATA-3', was, elevated, in, 'Th2', cells, as, determined, by, electrophorectic, mobility, shift, assay])]). relacion([sujeto(['In', 'contrast,', monocytes, from, normal, and, asthmatic, subjects]), verbo([expressed]), complemento(['GATA-4', and, -, 6, in, equal, 'amounts,', but, no, 'GATA-3', was, found])]). relacion([sujeto(['Using', immunohistochemistry, in, bronchial, 'biopsies,', epithelial, cells]), verbo([expressed]), complemento([high, levels, of, 'GATA-3,', 'GATA-4', and, 'GATA-6', proteins])]). relacion([sujeto(['In', 'conclusion,', the]), verbo([increased]), complemento([expression, of, 'GATA-3', in, asthmatic, 'T-cells', may, underlie, augmented, 'T-helper', 2, -, like, cytokines, in, this, disease])]). relacion([sujeto(['However,', the, unaltered, 'GATA-3', expression, in, epithelial, cells]), verbo([suggests]), complemento([a, distinct, role, for, 'GATA-3', in, these, cells, unrelated, to, 'T-helper', 2, -, like, cytokine, release])]). relacion([sujeto(['Finally,', no, evidence, was]), verbo([found]), complemento([for, an, increased, expression, of, 'GATA-4', and, 'GATA-6', in, asthma])]). relacion([sujeto(['The', objective, of, this, study, was, to, define, phenotypic, changes, of, 'antigen-presenting', cells, '(', 'APCs)', and, 'T', cells, in, a, murine, model, of, 'antigen-induced', airways, inflammation, that]), verbo([involves]), complemento([intraperitoneal, sensitization, with, ovalbumin, '(', 'OVA)/adjuvant', followed, by, antigen, aerosolization])]). relacion([sujeto(['After', 'sensitization,', this, expansion, was, comprised, mainly, of, 'B', 'cells,', a, considerable, proportion, of, which]), verbo([expressed]), complemento(['B7'])]). relacion([sujeto(['At', this, 'time,', 'T', cells, were, markedly, expanded, and]), verbo([activated]), complemento([as, assessed, by, 'CD69', 'expression;', 'further,', although, 'GATA-3', and, signal, transducer, and, activator, of, 'transcription-6', were, expressed, at, this, time, 'point,', expression, of, interleukin, '(', 'IL)-4,', 'IL-5,', and, 'IL-13', messenger, 'RNA', '(', 'mRNA)', levels, were, marginal])]). relacion([sujeto(['However,', in, vitro, stimulation, of, 'lymph-node', cells, with, 'OVA']), verbo([led]), complemento([to, cytokine, production])]). relacion([sujeto(['This', expansion, was]), verbo([associated]), complemento([with, enhanced, expression, of, both, 'B7'])]). relacion([sujeto(['We', also, observed, expansion, of]), verbo([activated]), complemento(['CD3(+)/CD4(+)', 'T', cells, expressing, the, 'T', 'helper-2-associated', marker, 'T1/ST2', in, the, 'lung,', most, notably, 5, d, after, challenge])]). relacion([sujeto(['Further,', 'IL-4,', 'IL-5,', and, 'IL-13,', but, not, 'interferon-gamma', mRNA, were]), verbo([expressed]), complemento([at, high, levels, 3, h, after, challenge])]). relacion([sujeto(['Interleukin-5', '(', 'IL-5)', is, a, 'T-cell', cytokine]), verbo([involved]), complemento([in, 'Type', 2, diseases, and, is, commonly, described, as, being, coordinately, regulated, with, other, 'Type', 2, 'cytokines,', such, as, 'IL-4', and, 'IL-13'])]). relacion([sujeto(['In', 'fact,', the, biological, specificity, of, eosinophilia, and, its, control, by, 'IL-5']), verbo([suggests]), complemento([a, unique, and, independent, control, of, 'IL-5', regulation])]). relacion([sujeto(['In', this]), verbo([report]), complemento([we, show, the, binding, of, 'GATA-3', to, three, sites, in, the, human, 'IL-5', promoter, in, the, human, 'T-cell', line, 'PER117'])]). relacion([sujeto(['The', previously, identified, -, 70, site, and, another, site, at, position, -, 152, are, shown, to, positively]), verbo([regulate]), complemento(['IL-5', transcription])]). relacion([sujeto(['More', 'importantly,', the, site, located, at, -, 400]), verbo([acts]), complemento([as, a, powerful, repressor, of, 'IL-5', transcription, with, mutagenesis, of, this, site, allowing, a, high, level, expression, of, 'IL-5', without, the, activation, of, other, factors, normally, required, for, 'IL-5', expression])]). relacion([sujeto(['Whereas', 'GATA-3']), verbo([has]), complemento([been, proposed, to, be, involved, in, the, regulation, of, the, 'IL-4/IL-5/IL-13', 'locus,', we, show, here, that, it, has, another, function, in, controlling, 'IL-5', transcription, that, supports, the, observed, unique, biological, function, of, this, cytokine])]). relacion([sujeto(['Recently,', a, member, of, the, 'GATA-binding', family, of, transcription, factors, was, shown, to, be]), verbo([involved]), complemento([in, the, human, 'hypoparathyroidism,', sensorineural, deafness, and, renal, anomalies, '(', 'HDR)', syndrome])]). relacion([sujeto(['We', wished, to, examine, the, effect, of, dexamethasone, on, the]), verbo([binding]), complemento([of, nuclear, factors, from, primary, human, 'CD4(+)', 'T', lymphocytes, to, the, 'RE-I', and, 'RE-II', positively, acting, regulatory, elements, of, the, 'IL-5', promoter])]). relacion([sujeto(['CD4(+)', 'T', 'cells,', purified, from, 'PBMCs', by, magnetic, bead, 'separation,', were]), verbo([activated]), complemento([with, 'anti-CD3', antibody, and, phorbol, myristate, acetate])]). relacion([sujeto(['In', extracts, from]), verbo([activated]), complemento(['cells,', the, 'RE-II', region, of, the, promoter, formed, a, complex, that, was, shown, by, supershift, assay, to, contain, 'NFATc'])]). relacion([sujeto(['By', 'contrast,']), verbo([binding]), complemento([to, the, 'RE-I', region, and, to, the, 'GATA-3', site, within, 'RE-I', was, observed, in, resting, cells, and, was, not, affected, by, activation, or, treatment, with, dexamethasone])]). relacion([sujeto(['Dexamethasone']), verbo([inhibits]), complemento([the, inducible, binding, of, factors, to, the, 'RE-II', region, but, does, not, affect, the, constitutive, binding, to, the, 'RE-I', region])]). relacion([sujeto(['Polycomb', group, '(', 'PcG)', gene, products]), verbo([regulate]), complemento([homeobox, gene, expression, in, 'Drosophila', and, vertebrates, and, also, cell, cycle, progression, of, immature, lymphocytes])]). relacion([sujeto(['Th2', cell, differentiation, was, 'impaired,', and, the, defect, was]), verbo([associated]), complemento([with, decreased, levels, in, demethylation, of, the, 'IL-4', gene])]). relacion([sujeto(['Three', 'GATA', family, transcription, factors, are]), verbo([involved]), complemento([in, various, aspects, of, hematopoiesis])]). relacion([sujeto(['The', selective, 'megakaryocytic/erythroid', differentiation, in, 'HSC', with, enforced, 'GATA-3', expression]), verbo([suggests]), complemento([a, functional, redundancy, among, 'GATA', proteins, and, indicates, that, the, specific, lineage, fate, determination, by, individual, 'GATA', proteins, is, largely, regulated, at, the, level, of, expression, in, a, lineage, and, 'developmental-stage', restricted, 'fashion,', whereas, the, identity, of, the, 'GATA', factor, may, not, be, as, important])]). relacion([sujeto(['In', 'CD2-GATA3-transgenic', 'mice,', large, fractions, of, peripheral, 'CD4(+)', 'T', cells]), verbo([expressed]), complemento([the, 'IL-1', receptor, family, member, 'T1/ST2,', indicative, of, advanced, 'Th2', commitment])]). relacion([sujeto(['In', contrast, to, 'wild-type', 'CD4(+)', 'cells,', which, lost, 'GATA-3', expression, when, cultured, under, 'Th1-polarizing', 'conditions,', 'CD2-GATA3-transgenic', 'CD4(+)', cells]), verbo([maintained]), complemento([expression, of, 'GATA-3', protein])]). relacion([sujeto(['Under', 'Th1', 'conditions,', cellular, proliferation, of, 'CD2-GATA3-transgenic', 'CD4(+)', cells, was, severely, 'hampered,', 'IFN-gamma', production, was]), verbo([decreased]), complemento([and, 'Th2', cytokine, production, was, increased])]). relacion([sujeto(['Enforced', 'GATA-3', expression]), verbo([inhibited]), complemento(['Th1-mediated', in, vivo, 'responses,', such, as, 'Ag-specific', 'IgG2a', production, or, a, 'delayed-type', hypersensitivity, response, to, keyhole, limpet, hemocyanin])]). relacion([sujeto(['Collectively,', these, observations, indicate, that, enforced, 'GATA-3', expression, selectively]), verbo([inhibits]), complemento(['Th1', differentiation, and, induces, 'Th2', differentiation])]). relacion([sujeto(['The']), verbo([increased]), complemento([functional, capacity, to, secrete, 'Th2', 'cytokines,', along, with, the, increased, expression, of, surface, markers, for, 'Ag-experienced', 'Th2-committed', 'cells,', would, argue, for, a, role, of, 'GATA-3', in, 'Th2', memory, formation])]). relacion([sujeto(['In', mice, carrying, a]), verbo([targeted]), complemento([insertion, of, a, lacZ, reporter, on, one, 'allele,', we, found, that, 'GATA-3', transcription, in, 'CD4(+)CD8(+)', 'double-positive', thymocytes, correlated, with, the, onset, of, positive, selection, 'events,', i])]). relacion([sujeto(['LacZ', expression, remained, high, '(', approximately, 80, '%', of, 'cells)', during, maturation, of, 'CD4', 'single-positive', '(', 'SP)', cells, in, the, 'thymus,', but, in, developing, 'CD8', 'SP', cells, the, fraction, of, 'lacZ-expressing', cells]), verbo([decreased]), complemento([to, &, 'lt;20%'])]). relacion([sujeto(['We', modified, this, pattern, by, enforced, 'GATA-3', expression, driven, by, the, 'CD2', locus, control, 'region,', which]), verbo([provides]), complemento([transcription, of, 'GATA-3', throughout, 'T', cell, development])]). relacion([sujeto(['In', 'tumor-free', 'CD2-GATA3-transgenic', 'mice,', the, total, numbers, of, 'CD8', 'SP', cells, in, the, thymus, were, within, normal, 'ranges,', but, their, maturation, was, 'hampered,', as, indicated, by]), verbo([increased]), complemento([apoptosis, of, 'CD8', 'SP', cells, and, a, selective, deficiency, of, mature, 'CD69(low)HSA(low)', 'CD8', 'SP', cells])]). relacion([sujeto(['These', findings, indicate, that, 'GATA-3', supports, development, of, the, 'CD4', lineage, and]), verbo([inhibits]), complemento([maturation, of, 'CD8', 'SP', cells, in, the, thymus])]). relacion([sujeto(['A', current, paradigm]), verbo([has]), complemento(['ICOS', participating, in, 'TH2', costimulation])]). relacion([sujeto(['New', data, indicates, 'ICOS']), verbo([regulates]), complemento([not, only, 'TH2', 'cells,', but, also, 'TH1s'])]). relacion([sujeto(['Endothelial', vascular, cell, adhesion, 'molecule-1', '(', 'VCAM-1)', is]), verbo([expressed]), complemento([in, response, to, cytokine, stimulation, and, plays, a, critical, role, in, inflammatory, reactions])]). relacion([sujeto(['Previously,', we, developed, a, novel, 'VCAM-1', inhibitor, that]), verbo([acts]), complemento([through, a, mechanism, independent, of, nuclear, 'factor-kappaB', activity])]). relacion([sujeto(['It']), verbo([suppresses]), complemento([the, binding, activity, of, 'GATA', proteins, in, 'cytokine-stimulated', endothelial, 'cells,', which, may, be, related, to, the, 'anti-VCAM-1', induction, effect, of, this, drug])]). relacion([sujeto(['The', mRNA, expression, of, 'GATA-6', was, 'increased,', whereas, 'GATA-3', mRNA, was]), verbo([decreased]), complemento([by, 'TNF-alpha', stimulation])]). relacion([sujeto(['Electrophoretic', mobility, shift, assay, showed, that, 'TNF-alpha', stimulation]), verbo([increased]), complemento([the, 'DNA', binding, of, 'GATA-6', but, decreased, that, of, 'GATA-3'])]). relacion([sujeto(['Experiments', using, protein, overexpression, or, antisense, oligonucleotides, revealed, that, 'GATA-6', potently]), verbo([acts]), complemento([as, a, positive, regulator, of, 'VCAM-1', gene, transcription])]). relacion([sujeto(['In', 'contrast,', overexpression, of, 'GATA-3', was, able, to]), verbo([suppress]), complemento(['TNF-alpha-induced', 'VCAM-1', expression])]). relacion([sujeto(['Our', results]), verbo([provide]), complemento([evidence, of, the, importance, of, 'GATA', proteins, in, the, induction, of, 'VCAM-1', by, 'TNF-alpha', in, vascular, endothelial, cells])]). relacion([sujeto(['In', response, to, 'IL-4,', the, 'IL-4R']), verbo([activates]), complemento([a, set, of, phosphotyrosine, binding, 'domain-containing', 'proteins,', including, insulin, receptor, substrate, 1, /, 2, ',', 'Shc,', and, 'IL-4R', interacting, 'protein,', as, well, as, 'Stat6'])]). relacion([sujeto(['Stat6']), verbo([has]), complemento([been, shown, to, be, required, for, 'Th2', differentiation])]). relacion([sujeto(['To', determine, the, roles, of, the, phosphotyrosine]), verbo([binding]), complemento([adaptors, in, 'Th2', 'differentiation,', we, prepared, a, retrovirus, containing, a, mutant, of, the, human, '(', 'h)IL-4R', 'alpha-chain,', 'Y497F,', which, is, unable, to, recruit, these, adaptors])]). relacion([sujeto(['Furthermore,', 'IL-4-driven', cell, expansion, was, also, normal, in, the, cells, infected, with, 'Y497F,', although, cells, infected, with, 'Y497F', were, not, capable, of]), verbo([phosphorylating]), complemento([insulin, receptor, substrate, 2])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, the, signal, pathway, mediated, by, 'Y497', is, dispensable, for, both, 'IL-4-driven', 'Th2', differentiation, and, cell, expansion])]). relacion([sujeto(['A', constitutively]), verbo([activated]), complemento([form, of, 'Stat6', introduced, into, 'CD4', 'T', cells, resulted, in, both, 'Th2', differentiation, and, enhanced, cell, expansion])]). relacion([sujeto(['Thus,']), verbo([activated]), complemento(['Stat6', is, necessary, and, sufficient, to, mediate, both, 'IL-4-driven', 'Th2', differentiation, and, cell, expansion, in, 'CD4', 'T', cells])]). relacion([sujeto(['Recent', studies, in, transgenic, mice]), verbo([have]), complemento([revealed, that, expression, of, a, dominant, negative, form, of, the, transcription, factor, 'GATA-3', in, 'T', cells, can, prevent, 'T', helper, cell, type, 2, '(', 'Th2)-mediated', allergic, airway, inflammation, in, mice])]). relacion([sujeto(['We', could]), verbo([suppress]), complemento(['GATA-3', expression, in, interleukin, '(', 'IL)-4-producing', 'T', cells, in, vitro, and, in, vivo, by, an, antisense, phosphorothioate, oligonucleotide, overlapping, the, translation, start, site, of, 'GATA-3,', whereas, nonsense, control, oligonucleotides, were, virtually, inactive])]). relacion([sujeto(['In', a, murine, model, of, asthma]), verbo([associated]), complemento([with, allergic, pulmonary, inflammation, and, hyperresponsiveness, in, ovalbumin, '(', 'OVA)-sensitized', 'mice,', local, intranasal, administration, of, fluorescein, 'isothiocyanate-labeled', 'GATA-3', antisense, oligonucleotides, led, to, 'DNA', uptake, in, lung, cells, associated, with, a, reduction, of, intracellular, 'GATA-3', expression])]). relacion([sujeto(['Such', intrapulmonary, blockade, of, 'GATA-3', expression]), verbo([caused]), complemento([an, abrogation, of, signs, of, lung, inflammation, including, infiltration, of, eosinophils, and, 'Th2', cytokine, production])]). relacion([sujeto(['Furthermore,', treatment, with, antisense, but, not, nonsense, oligonucleotides]), verbo([induced]), complemento([a, significant, reduction, of, airway, hyperresponsiveness, in, 'OVA-sensitized', mice, to, levels, comparable, to, 'saline-treated', control, 'mice,', as, assessed, by, both, enhanced, pause, '(', 'PenH)', responses, and, pulmonary, resistance, determined, by, body, plethysmography])]). relacion([sujeto(['These', data, indicate, a, critical, role, for, 'GATA-3', in, the, effector, phase, of, a, murine, asthma, model, and]), verbo([suggest]), complemento([that, local, delivery, of, 'GATA-3', antisense, oligonucleotides, may, be, a, novel, approach, for, the, treatment, of, airway, hyperresponsiveness, such, as, in, asthma])]). relacion([sujeto(['This', approach]), verbo([has]), complemento([the, potential, advantage, of, suppressing, the, expression, of, various, proinflammatory, 'Th2', cytokines, simultaneously, rather, than, suppressing, the, activity, of, a, single, cytokine])]). relacion([sujeto(['We']), verbo([report]), complemento([on, 'GATA3', analysis, and, the, phenotypic, spectrum, in, nine, 'Japanese', families, with, the, 'HDR', syndrome, '(', 'hypoparathyroidism,', sensorineural, 'deafness,', and, renal, 'dysplasia)', '(', 'MIM', 146255, ')'])]). relacion([sujeto(['Sequence', analysis, showed, heterozygous, novel, mutations, in, three, 'families:', a, missense, mutation, within, the, first, zinc, finger, domain, at, exon, 4, '(', 'T823A,', 'W275R),', an, unusual, mutation, at, exon, 4, '(', 900, insAA, plus, 901, insCCT, or, 'C901AACCCT)', resulting, in, a, premature, stop, at, codon, 357, with]), verbo([loss]), complemento([of, the, second, zinc, finger, 'domain,', and, a, nonsense, mutation, at, exon, 6, '(', 'C1099T,', 'R367X)'])]). relacion([sujeto(['The', results]), verbo([suggest]), complemento([that, 'HDR', syndrome, is, primarily, caused, by, 'GATA3', haploinsufficiency, and, is, associated, with, a, wide, phenotypic, spectrum])]). relacion([sujeto(['A', highly]), verbo([conserved]), complemento([sequence, block, '(', 'CSB)', located, in, the, mouse, and, human, 'T', cell, receptor, '(', 'TCR)', 'Jalpha', loci, is, recognized, by, 'tissue-specific', factors, and, 'up-regulates', 'TCR', alpha, enhancer, activity])]). relacion([sujeto(['Thymocytes', corresponding, to, different, developmental, stages, were]), verbo([found]), complemento([capable, of, forming, differential, 'CSB-nucleoprotein', complexes])]). relacion([sujeto(['Furthermore,', we, showed, that, transcription, factors, 'Oct-1,', 'Oct-2', and, 'GATA-3']), verbo([interacted]), complemento([with, 'CSB', both, in, 'vitro,', as, evidenced, by, electrophoretic, mobility, shift, 'assays,', and, in, 'vivo,', as, demonstrated, by, chromatin, immunoprecipitation, assays, in, mouse, thymus])]). relacion([sujeto(['Importantly,', we, also, demonstrated, that, 'GATA-3']), verbo([associated]), complemento([in, vivo, with, 'TCR', alpha, 'enhancer,', the, activity, of, which, is, known, to, be, required, in, regulating, chromatin, accessibility, to, the, 'V(D)J', recombinase])]). relacion([sujeto(['Thus,', 'CSB', may, temporally]), verbo([regulate]), complemento([local, chromatin, structure, and, help, to, spread, 'TCR', alpha, enhancer, activity, over, the, entire, 70, -, kb, 'Jalpha', locus, by, forming, developmentally, regulated, 'CSB-nucleoprotein', complexes, and, by, interacting, with, other, 'cis-regulatory', 'element-nucleoprotein', complexes, present, within, the, 'TCR', alpha, /, delta, locus])]). relacion([sujeto(['This', process, is, initiated, by, stimulation, with, antigen, and, the, cytokines, 'IL-12', and, 'IL-4,', 'respectively,', and]), verbo([requires]), complemento(['antigen-induced', transcription, factors, such, as, 'NFAT', and, 'cytokine-induced', transcription, factors, such, as, 'STAT4,', induced, by, 'IL-12,', and, 'STAT6,', induced, by, 'IL-4'])]). relacion([sujeto(['This', results, in, induction, and]), verbo([maintained]), complemento([expression, of, 'subset-specific', transcription, factors, including, 'T-bet', in, 'Th1', cells, and, 'GATA3', in, 'Th2', 'cells,', which, are, involved, in, ensuring, the, commitment, of, 'T-cells', to, 'Th1', or, 'Th2', lineages])]). relacion([sujeto(['Here', we, review, the, signalling, pathways, and, transcription, factors, that]), verbo([mediate]), complemento(['T-cell', 'differentiation,', and, describe, the, epigenetic, changes, in, chromatin, 'structure,', locus, accessibility, and, 'DNA', methylation, that, are, known, to, accompany, this, process])]). relacion([sujeto(['However,', when, these, distal, elements, were, combined, into, a, &, 'quot;minilocus,"', expression, was, strongly]), verbo([enhanced]), complemento([and, 'Th2', specific])]). relacion([sujeto(['GATA-3']), verbo([mediated]), complemento([strong, enhancement, of, 'IL-4', promoter, activity, in, 'Th1', cells, when, the, promoter, was, embedded, in, the, minilocus, or, linked, to, 'HSS', and, 'IE,', demonstrating, that, 'GATA-3', acts, through, these, elements, to, regulate, 'IL-4', gene, expression])]). relacion([sujeto(['This', is, due, in, part, to, the, relative, insensitivity, of, cytokine, detection, 'systems,', and]), verbo([associated]), complemento([variations, in, kinetics, of, cytokine, production, and, catabolism, in, in, vitro, culture, systems])]). relacion([sujeto(['Cord', blood, mononuclear, cells, were, 'Th1-', or, 'Th2-polarized', by, culture, in, 'IL-12-', or, 'IL-4-employing', established, 'methods;', 'PBMC', from, house, dust, mite, '(', 'HDM)-sensitive', atopics, and, controls, were]), verbo([stimulated]), complemento([overnight, with, 'HDM;', cytokine, production, was, measured, by, 'ELISA', and, 'GATA-3', mRNA, expression, by, 'PCR'])]). relacion([sujeto(['Cytokine-driven', 'Th2', polarization, of, naive, 'T', cells, is]), verbo([associated]), complemento([with, marked, upregulation, of, 'GATA-3', 'expression,', whereas, a, reciprocal, expression, pattern, accompanies, differentiation, towards, the, 'Th1', cytokine, phenotype])]). relacion([sujeto(['The', reciprocal, expression, pattern, observed, in, 'HDM-specific', recall, responses, of, 'non-atopics']), verbo([provides]), complemento([independent, confirmation, of, the, presence, of, underlying, 'Th1-like', immunity, in, these, subjects])]). relacion([sujeto(['The', parallel, findings, in, neonatal, 'T', cells]), verbo([suggest]), complemento([that, the, same, approach, may, be, utilized, for, monitoring, the, progress, of, 'allergen-specific', 'Th1/Th2', memory, development, during, early, 'childhood,', and, hence, in, assessment, of, risk, for, future, allergic, disease])]). relacion([sujeto(['Human', polarized, 'Th2', cells, do, not]), verbo([express]), complemento([the, signaling, 'beta2-subunit', of, the, 'IL-12R', 'and,', 'therefore,', do, not, signal, in, response, to, 'IL-12'])]). relacion([sujeto(['The', question, was, raised, as, to, what, extent, the]), verbo([loss]), complemento([of, the, 'IL-12Rbeta2', chain, in, 'Th2', cells, has, bearing, on, the, stability, of, the, human, 'Th2', phenotype])]). relacion([sujeto(['These', findings]), verbo([suggest]), complemento([the, possibility, of, restoring, 'IL-12', responsiveness, in, established, 'Th2', cells, of, atopic, patients, by, stimulation, in, the, presence, of, 'IL-12,', and, that, 'IL-12-promoting', immunotherapy, can, be, beneficial, for, 'Th2-mediated', immune, 'disorders,', targeting, both, naive, and, memory, effector, 'T', cells])]). relacion([sujeto(['The', expression, of, 'IL-4', and, 'IL-5', is]), verbo([increased]), complemento([in, patients, with, atopic, asthma, compared, with, control, subjects, and, correlates, with, indices, of, pulmonary, function])]). relacion([sujeto(['In', nonatopic, asthma, the, expression, of, 'IL-4,', unlike, 'IL-5,', fails, to, correlate, with, pulmonary, 'function,', and, compared, with, their, atopic, 'counterparts,', these, patients]), verbo([have]), complemento([fewer, cells, expressing, 'IL-4', receptor, '(', 'IL-4R)'])]). relacion([sujeto(['The', transcription, factors, 'GATA-3', and, cMAF]), verbo([mediate]), complemento(['IL-4', and, 'IL-5', 'synthesis,', whereas, signal, transducer, and, activator, of, transcription, 6, '(', 'STAT-6)', is, critical, for, 'IL-4R', signaling])]). relacion([sujeto(['Higher', numbers, of, cells]), verbo([expressing]), complemento(['GATA-3', and, cMAF, were, observed, in, patients, with, atopic, and, those, with, nonatopic, asthma, than, in, control, subjects, and, patients, with, tuberculosis, '(', 'P', &, 'lt;'])]). relacion([sujeto(['Notably,', 'however,', fewer, cells]), verbo([expressing]), complemento(['STAT-6', protein, were, observed, in, nonatopic, versus, atopic, asthma, '(', 'P', &, 'lt;'])]). relacion([sujeto(['Naive', 'CD4+', 'T', cells]), verbo([activated]), complemento([through, 'TCR/CD28', under, 'Th1', or, 'Th2', conditions, expressed, canonical, cytokine, patterns, irrespective, of, cell, division])]). relacion([sujeto(['Although', 'T', cells]), verbo([transcribed]), complemento([both, 'IFN-gamma', and, 'IL-4', within, hours, in, a, 'Stat4-/Stat6-independent', 'manner,', neither, 'T-bet', nor, 'GATA-3', was, induced, optimally, without, 'Stat', 'signals,', and, polarized, cytokine, expression, was, not, sustained])]). relacion([sujeto(['Development', of, 'Th2', subset, of, 'CD4+', 'T', cells]), verbo([involves]), complemento([the, 'interleukin-4', '(', 'IL-4)-', and, 'Stat6-dependent', increase, in, 'GATA-3', expression, during, primary, activation])]). relacion([sujeto(['Recently', we]), verbo([reported]), complemento([that, the, phenotypic, stability, and, factor, independence, of, 'Th2', cells, involves, acquisition, of, an, intracellular, pathway, that, maintains, 'GATA-3', expression])]). relacion([sujeto(['Evidence', from, retroviral, expression, studies, implied, that, this, pathway]), verbo([involved]), complemento([an, autoactivation, of, 'GATA-3', 'expression,', since, 'Stat6-deficient', 'T', cells, induced, endogenous, 'GATA-3', when, infected, with, 'GATA-3-expressing', retroviruses])]). relacion([sujeto(['Several', other, 'Th2-specific', transcription, factors]), verbo([have]), complemento([been, 'described,', including, 'c-Maf', and, 'JunB'])]). relacion([sujeto(['We', therefore, examined, the, ability, of, these, other, transcription, factors, to]), verbo([induce]), complemento(['GATA-3', expression, and, promote, 'Th2', development])]). relacion([sujeto(['Neither', 'c-Maf', nor, 'JunB']), verbo([induced]), complemento(['Th2', development, in, 'Stat6-deficient', 'CD4+', 'T', 'cells,', in, contrast, to, 'GATA-3'])]). relacion([sujeto(['Consistent', with, this, indication, of, a, possible, direct, autoactivation, 'pathway,', we, also, observed, that, heterologous, 'GATA', family, proteins, 'GATA-1,', 'GATA-2,', and, 'GATA-4', were, also, capable, of]), verbo([inducing]), complemento(['GATA-3', expression, in, developing, 'Stat6-deficient', 'T', cells, and, promote, 'Th2', development])]). relacion([sujeto(['IL-4', induction, by, 'GATA-3']), verbo([required]), complemento([each, of, the, functional, domains, to, be, 'present,', whereas, repression, of, gamma, interferon, could, occur, even, when, mutants, of, 'GATA-3', lacking, the, second, transactivation, 'domain,', 'TA2,', were, expressed])]). relacion([sujeto(['The', 'GATA-dependent', induction, of, the, 'GATA-3', but, not, the, other, 'GATA', genes, in, 'T', cells]), verbo([suggests]), complemento([that, 'T-cell-specific', cis, elements, within, the, 'GATA-3', locus, likely, cooperate, with, a, general, 'GATA', recognition, motif, to, allow, 'GATA-3-dependent', autoactivation])]). relacion([sujeto(['The', transcription, factor, 'GATA-3', is]), verbo([expressed]), complemento([in, 'T', helper, 2, '(', 'TH2)', but, not, 'TH1', cells, and, plays, a, critical, role, in, 'TH2', differentiation, and, allergic, airway, inflammation, in, vivo])]). relacion([sujeto(['Mice', that, lack, the, p50, subunit, of]), verbo([nuclear]), complemento([factor, kappa, 'B', '(', 'NF-kappa', 'B)', are, unable, to, mount, airway, eosinophilic, inflammation])]). relacion([sujeto(['CD4+', 'T', cells, from, 'p50-/-', mice, failed, to]), verbo([induce]), complemento(['Gata3', expression, under, 'TH2-differentiating', conditions, but, showed, unimpaired, 'T-bet', expression, and, interferon, gamma, '(', 'IFN-gamma)', production, under, 'TH1-differentiating', conditions])]). relacion([sujeto(['Inhibition', of, 'NF-kappa', 'B', activity]), verbo([prevented]), complemento(['GATA-3', expression, and, 'TH2', cytokine, production, in, 'developing,', but, not, 'committed,', 'TH2', cells])]). relacion([sujeto(['Our', studies]), verbo([provide]), complemento([a, molecular, basis, for, the, need, for, both, 'T', cell, receptor, and, cytokine, signaling, for, 'GATA-3', expression, 'and,', in, 'turn,', 'TH2', differentiation])]). relacion([sujeto(['Different', transcription, factors]), verbo([have]), complemento([been, shown, to, control, the, transition, of, naive, 'T', cells, into, 'T', helper, 1, '(', 'Th1)/Th2', subsets])]). relacion([sujeto(['The', 'T-cell-specific', transcription, factor, 'GATA-3', is, known, to, be, selectively]), verbo([expressed]), complemento([in, murine, developing, 'Th2', cells, and, to, exert, a, positive, action, on, 'Th2-specific', cytokine, production])]). relacion([sujeto(['Investigating', 'GATA-3', gene, regulation, in, human, 'T', cells, we]), verbo([have]), complemento([found, that, naive, 'T', cells, highly, express, 'GATA-3,', and, during, early, 'T2', or, 'T1', 'polarization,', 'respectively,', they, either, maintain, or, quickly, 'down-regulate', expression])]). relacion([sujeto(['In', developing, 'T2', 'cells,', as, well, as, in, committed, 'Th2', cell, lines, and, 'clones,', we]), verbo([found]), complemento([a, positive, correlation, among, 'GATA-3,', interleukin, '(', 'IL)-5', and, 'IL-4', gene, expression, 'kinetics,', supporting, the, positive, action, of, 'GATA-3', on, 'Th2-specific', cytokine, production])]). relacion([sujeto(['During', 'T-cell', commitment, the, presence, of, 'IL-4', in, the, culture, was, essential, to]), verbo([maintain]), complemento([or, enhance, 'GATA-3', 'transcription,', while, 'IL-12', was, not, necessary, for, full, repression, of, 'GATA-3'])]). relacion([sujeto(['Although', interleukin, '(', 'IL)-12', and, 'IL-4', polarize, naive, 'CD4(+)', 'T', cells, toward, 'T', helper, cell, type, 1, '(', 'Th1)', or, 'Th2', 'phenotypes,', it, is, not, known, whether, cytokines, instruct, the, developmental, fate, in, uncommitted, progenitors, or, select, for, outgrowth, of, cells, that]), verbo([have]), complemento([stochastically, committed, to, a, particular, fate])]). relacion([sujeto(['We', observe, 'IL-4-dependent', redirection, of, phenotype, in, cells, that]), verbo([have]), complemento([already, committed, to, a, 'non-IL-4-producing', 'fate,', inconsistent, with, predictions, of, the, selective, model])]). relacion([sujeto(['Further,', retroviral, tagging, of, naive, progenitors, with, the, 'Th2-specific', transcription, factor, 'GATA-3']), verbo([provided]), complemento([direct, evidence, for, instructive, 'differentiation,', and, no, evidence, for, the, selective, outgrowth, of, cells, committed, to, either, the, 'Th1', or, 'Th2', fate])]). relacion([sujeto(['In', 'summary,', a, multitude, of, regulatory, systems, are, employed, to]), verbo([cause]), complemento([the, selective, activation, of, target, cytokine, genes, in, 'Th1', and, 'Th2', effector, cells])]). relacion([sujeto(['These', mechanisms]), verbo([involve]), complemento([both, positive, and, negative, regulation, and, employ, at, least, three, kinds, of, mechanisms])]). relacion([sujeto(['Finally,', the, selective, use, of, signaling, 'pathways,', in, the, case, studied, here, 'MAP', kinase, 'pathways,']), verbo([leads]), complemento([to, the, selective, activation, of, target, genes])]). relacion([sujeto(['We', believe, that, transcriptional, 'up-regulation', of, rac2]), verbo([leads]), complemento([to, the, coupling, of, both, the, p38, and, 'JNK', 'MAP', kinase, pathways, to, the, 'T-cell', receptor, 'and/or', costimulatory, 'receptors,', thereby, providing, a, 'lineage-specific', signal])]). relacion([sujeto(['CD4', cells, from, mice, heterozygous, for, an, 'IL-4', and, a, 'GFP/IL-4', gene, frequently]), verbo([express]), complemento([a, single, allele])]). relacion([sujeto(['Analysis', of, 'IL-4', or, 'GFP', production, by, cells, from, recently, primed, 'Th2', cells, indicates, that, essentially, all, are, competent, to]), verbo([transcribe]), complemento([either, allele, but, have, a, low, probability, of, doing, so])]). relacion([sujeto(['By', 'contrast,', 'long-term', 'Th2', clones, show, distinct, and, heritable, ratios, in, the, proportion, of, cells, that]), verbo([express]), complemento(['IL-4', or, 'GFP'])]). relacion([sujeto(['Previously,', we]), verbo([found]), complemento([that, the, conversion, of, hemoglobins, '(', 'Hbs)', from, the, larval, to, the, adult, type, occurred, within, a, single, erythroid, cell, population, in, a, 'salamander,', 'Hynobius', retardatus, '(', &, 'quot;Hb', 'switching"', 'model),', whereas, the, transition, involves, replacement, of, 'red-blood-cell', '(', 'RBC)', populations, '(', &, 'quot;RBC', 'replacement"', 'model)', in, many, amphibians, '(', 'M'])]). relacion([sujeto(['To', further, characterize, the, 'Hb', 'transition,', developmental, changes, in, the, erythropoietic, sites]), verbo([have]), complemento([been, intensively, analyzed, using, 'larval-', and, 'adult-specific', globin, antibodies, and, globin, and, 'GATA-3', 'RNA', probes])]). relacion([sujeto(['Cells', of, the, ventral, blood, island, '(', 'VBI)', and, the, dorsolateral, plate, '(', 'DLP)', in, embryos, differentiate, in, situ, to, erythroid, cells, that, contain, larval, globin, 'mRNA,']), verbo([suggesting]), complemento([that, both, the, 'VBI', and, the, 'DLP', contribute, to, &, 'quot;primitive"', erythropoiesis])]). relacion([sujeto(['In', 'contrast,', the, expression, pattern, of, the, 'GATA-3', gene]), verbo([suggests]), complemento([that, cells, of, the, 'DLP', may, contribute, to, &, 'quot;definitive"', hematopoiesis])]). relacion([sujeto([retardatus, or, 'not,', further, experiments, were, 'done:', '(', 1, ')', when, metamorphosing, larvae, were, treated, with, phenylhydrazine, to]), verbo([induce]), complemento([anemia, and, then, bled, at, the, postmetamorphic, stage, after, recovery, from, the, 'anemia,', a, precocious, 'Hb', transition, was, observed, in, these, 'animals;', '(', 2, ')', an, 'RBC', population, expressing, only, adult, 'Hb', was, confirmed, by, subtracting, the, number, of, 'RBCs', expressing, larval, 'Hb', from, the, total, number, of, 'RBCs', during, metamorphosis])]). relacion([sujeto(['Recently,', it, was, shown, that, the, expression, of, 'GATA-3', is, further]), verbo([induced]), complemento([in, 'CD4+', helper, 'T', cells, upon, differentiation, into, type, 2, but, not, type, 1, effector, cells])]). relacion([sujeto(['Here,', we]), verbo([report]), complemento([the, molecular, cloning, of, a, 'GATA-3', interacting, 'protein,', repressor, of, 'GATA', '(', 'ROG)'])]). relacion([sujeto(['ROG', is, a, 'lymphoid-specific', gene, and, is, rapidly]), verbo([induced]), complemento([in, 'Th', cells, upon, stimulation, with, 'anti-CD3'])]). relacion([sujeto(['Furthermore,', overexpression, of, 'ROG', in, 'Th', clones]), verbo([inhibits]), complemento([the, production, of, 'Th', cytokines])]). relacion([sujeto(['Taken', 'together,', our, results]), verbo([suggest]), complemento([that, 'ROG', might, play, a, critical, role, in, regulating, the, differentiation, and, activation, of, 'Th', cells])]). relacion([sujeto(['Patterning', the, vertebrate, ear]), verbo([requires]), complemento([the, coordinated, expression, of, genes, that, are, involved, in, 'morphogenesis,', 'neurogenesis,', and, hair, cell, formation])]). relacion([sujeto(['The', zinc, finger, gene, 'GATA-3', is]), verbo([expressed]), complemento([both, in, the, inner, ear, and, in, afferent, and, efferent, auditory, neurons])]). relacion([sujeto(['Specifically,', 'GATA-3', is]), verbo([expressed]), complemento([in, a, population, of, neurons, in, rhombomere, 4, that, extend, their, axons, across, the, floor, plate, of, rhombomere, 4, '(', 'r4)', at, embryonic, day, 10, '(', 'E10)', and, reach, the, sensory, epithelia, of, the, ear, by, 'E13'])]). relacion([sujeto(['This']), verbo([suggests]), complemento([that, 'GATA-3', is, involved, in, the, pathfinding, of, efferent, neuron, axons, that, navigate, to, the, ear])]). relacion([sujeto(['In', the, 'ear,', 'GATA-3', is]), verbo([expressed]), complemento([inside, the, otocyst, and, the, surrounding, periotic, mesenchyme])]). relacion([sujeto(['The', latter, expression, is, in, areas, of, branching, of, the, developing, ear]), verbo([leading]), complemento([to, the, formation, of, semicircular, canals])]). relacion([sujeto(['Thus,', both, the, distribution, of, 'GATA-3', and, the, effects, of, null, mutations, on, the, ear]), verbo([suggest]), complemento([involvement, of, 'GATA-3', in, morphogenesis, of, the, ear])]). relacion([sujeto(['This', study, shows, for, the, first, time, that, a, zinc, finger, factor, is]), verbo([involved]), complemento([in, axonal, navigation, of, the, inner, ear, efferent, neurons, 'and,', 'simultaneously,', in, the, morphogenesis, of, the, inner, ear])]). relacion([sujeto(['DC', of, myeloid, origin, capture, antigens, in, 'tissues,', migrate, to, lymphoid, organs, and]), verbo([stimulate]), complemento(['T', cell, responses])]). relacion([sujeto(['A', subset, of, 'DC']), verbo([has]), complemento([been, described, which, expresses, lymphoid, determinants, and, has, potential, regulatory, functions])]). relacion([sujeto(['Conditional', transformation, of, chicken, bone, marrow, progenitors, with, 'v-relER,', a, 'v-rel', estrogen, receptor, '(', 'ER)', fusion, 'gene,', allows, expansion, of, progenitors, that, can, be]), verbo([induced]), complemento([to, differentiate, into, 'DC', in, vitro])]). relacion([sujeto(['These', data]), verbo([suggest]), complemento([that, 'v-relER', 'DC', might, be, related, to, the, lymphoid, subset, of, 'DC', described, in, mammals])]). relacion([sujeto(['Here', we, show, that, ectopic, expression, and, activation, of, 'Stat6', or, 'GATA-3', in, 'Th', cells, developing, under, 'Th1-polarizing', conditions]), verbo([lead]), complemento([to, the, induction, of, chromatin, remodeling, not, only, at, the, flanking, regions, of, the, 'IL-4', and, 'IL-13', genes, but, also, at, the, 'IL-4/IL-13', intergenic, regulatory, region, for, the, 'IL-4/IL-13/IL-5', gene, cluster])]). relacion([sujeto(['Furthermore,', we, demonstrate, that, 'GATA-3', and, another, 'Th2-specific,', inducible, protein, complex]), verbo([interact]), complemento([with, the, 'IL-4/IL-13', intergenic, 'DNase', 'I', hypersensitive, region, specifically, in, 'Th2', cells])]). relacion([sujeto(['These', intraembryonic, precursors]), verbo([have]), complemento([previously, been, demonstrated, to, include, cells, that, harbour, 'T-cell', progenitor, capacity, and, express, the, 'Ikaros', transcription, 'factor,', known, to, be, a, prerequisite, for, lymphocyte, development])]). relacion([sujeto(['We', show, that, early, intraembryonic, cells, and, prethymic, progenitors, already]), verbo([express]), complemento([the, 'GATA-3', transcription, factor])]). relacion([sujeto(['However,', these, intraembryonic, cells]), verbo([retain]), complemento([their, 'T-cell', receptor, gamma, loci, in, germline, configuration])]). relacion([sujeto(['Interestingly,', chTcf, was]), verbo([found]), complemento([to, express, different, alternatively, spliced, isoforms, during, early, ontogeny, and, thymic, 'T-cell', 'development,', which, indicates, developmentally, regulated, expression, of, chTcf, variants])]). relacion([sujeto(['Taken', 'together,', these, results, demonstrate, 'that,', although, the, avian, prethymic, progenitor, cells]), verbo([express]), complemento(['T-lineage-associated', transcription, 'factors,', they, have, not, yet, undergone, 'TCR', rearrangements])]). relacion([sujeto(['It', is, therefore]), verbo([suggested]), complemento([that, activation, of, 'lineage-associated', genes, is, an, early, event, in, the, generation, of, haematopoietic, progenitor, cells, during, ontogeny])]). relacion([sujeto(['This', outcome, could, not]), verbo([have]), complemento([been, predicted, by, the, commonly, used, histoclinical, parameters])]). relacion([sujeto(['No', correlation, was]), verbo([found]), complemento([with, the, age, of, 'patients,', tumor, 'size,', histological, type, and, grade])]). relacion([sujeto(['Thus,', our, results, identified, new, ways, to, group, tumors, according, to, outcome, and, new, potential]), verbo([targets]), complemento([of, carcinogenesis])]). relacion([sujeto(['They', show, that, the, systematic, use, of, cDNA, array, testing, holds, great, promise, to, improve, the, classification, of, breast, cancer, in, terms, of, prognosis, and, chemosensitivity, and, to]), verbo([provide]), complemento([new, potential, therapeutic, targets])]). relacion([sujeto(['We']), verbo([have]), complemento([identified, a, novel, 'Kruppel-type', zinc, finger, '(', 'ZF)', 'gene,', 'SKAT-2,', which, is, selectively, expressed, by, murine, 'Th2', cells])]). relacion([sujeto(['The', protein, encoded, by, this, gene]), verbo([has]), complemento([14, 'C2H2-type', 'ZF', tandemly, arrayed, at, its, 'C', terminus, and, 'N-terminal', 'SCAN', box, and, 'KRAB', domains])]). relacion([sujeto(['By', in, situ, 'hybridization,', 'SKAT-2', expression, was]), verbo([found]), complemento([to, peak, in, 'antigen-stimulated', 'CD4(+)', 'T', cells, after, 2, -, 3, days, of, culture, under, 'Th2', but, not, 'Th1', biasing, conditions])]). relacion([sujeto(['In', transient, transfection, experiments, in, phorbol, 12, -, myristate, 13, -, 'acetate/ionomycin-stimulated', 'EL4', 'cells,', 'SKAT-2', was]), verbo([found]), complemento([to, 'up-regulate', the, activity, of, the, 'IL-4', but, not, the, 'IL-5', 'promoter,', contrasting, with, the, ability, of, 'GATA-3', to, activate, both, promoters])]). relacion([sujeto(['This', result, was, confirmed, using, clones, of, 'EL4', cells, stably]), verbo([expressing]), complemento([an, inducible, form, of, 'SKAT-2,', thus, 'SKAT-2', is, a, novel, 'Th2-specific', gene, that, may, play, a, role, in, selective, regulation, of, cytokine, genes, in, 'T', cells])]). relacion([sujeto(['Drosophila', 'GCM', is, a, neural, transcription, factor, that]), verbo([regulates]), complemento([glial, cell, fate])]). relacion([sujeto(['Several', potential]), verbo([binding]), complemento([sites, for, transcription, factors, like, 'GATA,', 'Oct-1,', and, bHLH, proteins, were, found, in, the, 5, '\'', -, flanking, region, of, the, human, gene])]). relacion([sujeto(['A', 'DNA', motif, for, 'GCM', protein]), verbo([binding]), complemento([exists, in, the, 5, '\'', -, flanking, region, that, is, highly, homologous, with, that, of, the, mouse, gene])]). relacion([sujeto(['Elevation', of, intracellular, cAMP, in, 'T', 'cells,']), verbo([induced]), complemento([by, agents, such, as, 'IL-1alpha', or, 'PGs,', inhibits, 'T', cell, activation])]). relacion([sujeto(['In', effector, 'T', 'cells,', an]), verbo([increase]), complemento([in, the, level, of, intracellular, cAMP, inhibits, cytokine, production, in, 'Th1', cells, but, stimulates, cytokine, production, in, 'Th2', cells])]). relacion([sujeto(['Here', we]), verbo([report]), complemento([that, 'cAMP-induced', effects, in, 'Th2', cells, occur, independently, of, the, protein, kinase, 'A', 'pathway,', which, is, the, major, mediator, of, 'cAMP-induced', signaling, events, in, most, cell, types])]). relacion([sujeto(['Instead,', cAMP]), verbo([stimulates]), complemento([activation, of, p38, 'mitogen-activated', protein, kinase, in, 'Th2', cells])]). relacion([sujeto(['This', appears, to, be, a, 'Th2-selective', event, because, cAMP, barely]), verbo([increased]), complemento([p38, phosphorylation, in, 'Th1', cells])]). relacion([sujeto(['We', show, that, in, 'Th2', 'cells,', cAMP]), verbo([promotes]), complemento([the, production, of, both, 'IL-5', and, 'IL-13,', which, play, distinct, but, critical, roles, in, asthma, pathogenesis])]). relacion([sujeto(['Our', data, also, show, that, cAMP]), verbo([causes]), complemento([increased, phosphorylation, of, the, transcription, factor, 'GATA-3,', which, we, have, shown, is, a, critical, regulator, of, 'Th2', cytokine, gene, expression, 'and,', in, 'turn,', of, airway, inflammation, in, mice])]). relacion([sujeto(['Thus,', 'Th2-specific', 'GATA-3', expression, and, p38, 'mitogen-activated', protein, kinase, activation, together]), verbo([provide]), complemento([a, molecular, basis, for, the, differential, effects, of, cAMP, in, the, two, 'T', helper, cell, subsets])]). relacion([sujeto(['TGF-beta', is, an, important, immunomodulatory, cytokine, that, can]), verbo([inhibit]), complemento([differentiation, of, effector, 'T', cells])]). relacion([sujeto(['In', this, 'report,', we, address, the, molecular, mechanisms, through, which, 'TGF-beta']), verbo([inhibits]), complemento([differentiation, of, 'CD4(+)', cells, into, 'Th', type, 2, cells])]). relacion([sujeto(['We', demonstrate, that, 'TGF-beta']), verbo([inhibits]), complemento(['GATA-3', expression, in, developing, 'Th', cells])]). relacion([sujeto(['We', also, show, that, inhibition, of, 'GATA-3', expression, by, 'TGF-beta', is, a, major, mechanism, of, inhibition, of, 'Th2', differentiation, by, 'TGF-beta', as, ectopic, expression, of, 'GATA-3', in, developing, 'T', cells, overcomes, the, ability, of, 'TGF-beta', to]), verbo([inhibit]), complemento(['Th2', differentiation])]). relacion([sujeto(['TGF-beta', likely]), verbo([inhibits]), complemento(['GATA-3', expression, at, the, transcriptional, level, and, does, so, without, interfering, with, 'IL-4', signaling])]). relacion([sujeto(['The', 'T', helper, subsets, 'Th1', and, 'Th2']), verbo([regulate]), complemento([specific, types, of, immune, responses, by, producing, distinct, sets, of, cytokines])]). relacion([sujeto(['Differentiation', of, the, 'T', helper, subsets, from, their, common, 'precursors,', naive, 'CD4+', 'T', 'cells,', is]), verbo([induced]), complemento([by, antigen, stimulation, and, controlled, by, various, other, conditions])]). relacion([sujeto(['Of', these, 'conditions,', the, contributions, of, the, cytokine, environment]), verbo([have]), complemento([been, the, best, characterized])]). relacion([sujeto(['The', presence, of, 'interleukin-4', '(', 'IL-4)', directs, the, differentiation, towards, 'Th2', 'cells,', whereas, 'IL-12']), verbo([induces]), complemento(['Thl', differentiation])]). relacion([sujeto(['The', 'Th2', signature, cytokine, genes, encoding, 'IL-4,', 'IL-13,', and, 'IL-5', are, 'clustered,', and, noncoding, regions, such, as, the, intergenic, region, of, the, 'IL-4', and, 'IL-13', genes, are, highly]), verbo([conserved]), complemento([from, mice, to, humans])]). relacion([sujeto(['Activation', of, 'STAT6']), verbo([promotes]), complemento(['Th2', differentiation, by, inducing, 'Th2-specific', transcription, 'factors,', including, 'GATA3'])]). relacion([sujeto(['Expression', of, 'GATA3']), verbo([induces]), complemento(['Th2', differentiation, and, enhances, the, 'Th2', 'cell-specific', chromatin, 'accessibility,', indicating, that, 'GATA3', is, a, key, protein, that, regulates, differentiation, through, chromatin, remodeling])]). relacion([sujeto(['T', helper, subset, differentiation]), verbo([provides]), complemento([a, good, system, to, study, gene, expression, regulation, at, the, chromatin, level])]). relacion([sujeto(['Here,', we, show, that, murine, 'GATA-2', and, 'GATA-3', are, specifically]), verbo([expressed]), complemento([in, white, adipocyte, precursors, and, that, their, 'down-regulation', sets, the, stage, for, terminal, differentiation])]). relacion([sujeto(['Constitutive', 'GATA-2', and, 'GATA-3', expression]), verbo([suppressed]), complemento([adipocyte, differentiation, and, trapped, cells, at, the, preadipocyte, stage])]). relacion([sujeto(['GATA-3-deficient', embryonic, stem, cells, exhibit, an]), verbo([enhanced]), complemento([capacity, to, differentiate, into, 'adipocytes,', and, defective, 'GATA-2', and, 'GATA-3', expression, is, associated, with, obesity])]). relacion([sujeto(['Thus,', 'GATA-2', and, 'GATA-3']), verbo([regulate]), complemento([adipocyte, differentiation, through, molecular, control, of, the, 'preadipocyte-adipocyte', transition])]). relacion([sujeto(['Here', we, describe, how, 'TGF-beta']), verbo([modulates]), complemento(['Th2', development, in, vitro, and, investigate, its, mechanisms, of, action])]). relacion([sujeto(['We', 'found,', 'however,', that, naive, cells, driven, in, 'Th2', conditions, with, 'TGF-beta', did, not, show, a, significantly]), verbo([decreased]), complemento(['STAT6', 'activation,', suggesting, that, 'TGF-beta', inhibits, 'Th2', development, via, a, 'STAT6-independent', mechanism])]). relacion([sujeto(['Given', the, key, role, of, 'GATA-1', transcription, factor, in, fetal, globin, gene, promoter, 'activity,', we, investigated, whether, specific, 'GATA', family, members, are]), verbo([expressed]), complemento([in, the, prostate, and, whether, they, can, regulate, 'prostate-specific', genes])]). relacion([sujeto(['We']), verbo([found]), complemento([that, 'GATA-2', and, -, 3, are, the, predominant, 'GATA', family, members, expressed, in, human, and, mouse, prostate, and, that, 'GATA', mRNA, levels, are, not, regulated, by, androgen])]). relacion([sujeto(['These', 'GATA', sites, are]), verbo([targets]), complemento([for, 'GATA', factors, and, are, essential, for, optimal, androgen, induction, of, transfected, 'PSA', 'enhancer/promoter', plasmids, in, 'LNCaP,', a, 'PSA', and, androgen, receptor, expressing, human, prostate, cancer, cell, line])]). relacion([sujeto(['Our', results]), verbo([suggest]), complemento([that, prostatic, 'GATA-2', and, -, 3, are, involved, in, the, androgen, regulation, of, the, 'PSA', gene])]). relacion([sujeto(['Erythropoietin', '(', 'Epo)', is]), verbo([required]), complemento([for, the, production, of, mature, red, blood, cells])]). relacion([sujeto(['The', requirement, for, 'Epo', and, its, receptor, '(', 'EpoR)', for, normal, heart, development, and, the, response, of, vascular, endothelium, and, cells, of, neural, origin, to, 'Epo']), verbo([provide]), complemento([evidence, that, the, function, of, 'Epo', as, a, growth, factor, or, cytokine, to, protect, cells, from, apoptosis, extends, beyond, the, hematopoietic, lineage])]). relacion([sujeto(['We', now]), verbo([report]), complemento([that, the, 'EpoR', is, expressed, on, myoblasts, and, can, mediate, a, biological, response, of, these, cells, to, treatment, with, 'Epo'])]). relacion([sujeto(['Primary', murine, satellite, cells, and, myoblast, 'C2C12', 'cells,', both, of, which]), verbo([express]), complemento([endogenous, 'EpoR,', exhibit, a, proliferative, response, to, 'Epo', and, a, marked, decrease, in, terminal, differentiation, to, form, myotubes])]). relacion([sujeto(['We', also, observed, that, 'Epo', stimulation]), verbo([activates]), complemento(['Jak2/Stat5', signal, transduction, and, increases, cytoplasmic, 'calcium,', which, is, dependent, on, tyrosine, phosphorylation])]). relacion([sujeto(['In', erythroid, progenitor, 'cells,', 'Epo']), verbo([stimulates]), complemento([induction, of, transcription, factor, 'GATA-1', and, 'EpoR;', in, 'C2C12', 'cells,', 'GATA-3', and, 'EpoR', expression, are, induced])]). relacion([sujeto(['The']), verbo([decrease]), complemento([in, differentiation, of, 'C2C12', cells, is, concomitant, with, an, increase, in, 'Myf-5', and, 'MyoD', expression, and, inhibition, of, myogenin, induction, during, 'differentiation,', altering, the, pattern, of, expression, of, the, 'MyoD', family, of, transcription, factors, during, muscle, differentiation])]). relacion([sujeto(['These', data]), verbo([suggest]), complemento(['that,', rather, than, acting, in, an, instructive, or, specific, mode, for, 'differentiation,', 'Epo', can, stimulate, proliferation, of, myoblasts, to, expand, the, progenitor, population, during, differentiation, and, may, have, a, potential, role, in, muscle, development, or, repair])]). relacion([sujeto(['Acetylation', of, a, transcription, factor]), verbo([has]), complemento([recently, been, shown, to, play, a, significant, role, in, gene, regulation])]). relacion([sujeto(['These', findings]), verbo([have]), complemento([significant, implications, in, that, the, acetylation, state, of, 'GATA-3', affects, its, physiological, function, in, the, immune, system, 'and,', more, 'importantly,', provides, evidence, for, the, novel, role, of, 'GATA-3', in, 'T-cell', survival, and, homing, to, secondary, lymphoid, organs])]). relacion([sujeto(['Studies', in, patients, with, 10, p, deletions]), verbo([have]), complemento([defined, two, 'non-overlapping', regions, that, contribute, to, this, complex, phenotype])]). relacion([sujeto(['We']), verbo([have]), complemento([performed, 'deletion-mapping', studies, in, two, 'HDR', 'patients,', and, here, we, define, a, critical, 200, -, kilobase, region, which, contains, the, 'GATA3', gene])]). relacion([sujeto(['This', gene, belongs, to, a, family, of, 'zinc-finger', transcription, factors, that, are]), verbo([involved]), complemento([in, vertebrate, embryonic, development])]). relacion([sujeto(['Investigation', for, 'GATA3', mutations, in, three, other, 'HDR', probands, identified, one, nonsense, mutation, and, two, intragenic, deletions, that, predicted, a]), verbo([loss]), complemento([of, 'function,', as, confirmed, by, absence, of, 'DNA', binding, by, the, mutant, 'GATA3', protein])]). relacion([sujeto(['These', results, show, that, 'GATA3', is, essential, in, the, embryonic, development, of, the, 'parathyroids,', auditory, system, and, 'kidneys,', and, indicate, that, other, 'GATA', family, members, may, be]), verbo([involved]), complemento([in, the, aetiology, of, human, malformations])]). relacion([sujeto(['GATA-1', germline, mutation, in, mice, results, in, embryonic, lethality, due, to, defective, erythroid, cell, 'maturation,', and, thus, other, hematopoietic, 'GATA', factors, do, not, compensate, for, the]), verbo([loss]), complemento([of, 'GATA-1'])]). relacion([sujeto(['We']), verbo([found]), complemento([that, transgenic, expression, of, a, 'GATA-1', cDNA, fully, abrogated, the, 'GATA-1-deficient', phenotype])]). relacion([sujeto(['Surprisingly,', 'GATA-2', and, 'GATA-3', factors]), verbo([expressed]), complemento([from, the, same, regulatory, cassette, also, rescued, the, embryonic, lethal, phenotype, of, the, 'GATA-1', mutation])]). relacion([sujeto(['By', 'DNase', 'I', hypersensitivity, 'analysis,', we]), verbo([have]), complemento([identified, an, 'inducible,', cyclosporin, 'A-sensitive', enhancer, located, 3, '\'', of, the, 'interleukin-4', '(', 'IL-4)', gene])]). relacion([sujeto(['The', enhancer]), verbo([binds]), complemento([the, 'Th2-specific', transcription, factor, 'GATA3', in, vivo, but, is, not, perceptibly, influenced, by, the, absence, of, a, second, 'Th2-specific', 'factor,', cMaf])]). relacion([sujeto(['The', 'antigen-inducible', transcription, factor, 'NFAT1']), verbo([binds]), complemento([the, 'IL-4', enhancer, and, the, 'IL-4', promoter, only, in, stimulated, 'Th2', 'cells;', 'conversely,', 'NFAT1', binds, to, the, interferon, '(', 'IFN)-gamma', promoter, only, in, stimulated, 'Th1', cells])]). relacion([sujeto(['Our', results, support, a, model, whereby, transcription, factors, such, as, 'NFAT1,', which, are, nonselectively]), verbo([induced]), complemento([in, 'antigen-stimulated', 'T', 'cells,', gain, access, to, cytokine, regulatory, regions, only, in, the, appropriate, subset, of, differentiated, 'T', cells, in, vivo])]). relacion([sujeto(['Committed', 'Th1', cells, cannot, be]), verbo([induced]), complemento([to, change, their, cytokine, profiles, in, response, to, antigenic, stimulation, and, 'Th2', 'cytokine-inducing', conditions])]). relacion([sujeto(['Here,', we]), verbo([report]), complemento([that, ectopic, expression, of, 'GATA-3', induced, 'Th2-specific', cytokine, expression, not, only, in, developing, 'Th1', cells, but, also, in, otherwise, irreversibly, committed, 'Th1', cells, and, a, 'Th1', 'clone,', 'HDK1'])]). relacion([sujeto(['Ectopic', expression, of, 'GATA-3', in, developing, 'Th1', 'cells,', but, not, in, 'Th1', clone, 'HDK1,']), verbo([induced]), complemento([endogenous, 'GATA-3,', suggesting, an, autoregulatory, mechanism, for, maintenance, of, 'GATA-3', expression, in, 'Th2', cells])]). relacion([sujeto(['Both', zinc, 'fingers,', 'however,', were]), verbo([required]), complemento([for, 'IL-5', induction])]). relacion([sujeto(['Given', the, critical, role, of, cytokines, in, the, regulation, of, an, inflammatory, 'response,', we, investigated, whether, certain, cytokines, are]), verbo([expressed]), complemento([in, the, brains, of, normal, mice, during, maturation, that, could, contribute, to, the, 'immune-privileged', nature, of, the, 'CNS', or, potentially, influence, an, 'immune-mediated', illness, such, as, experimental, allergic, encephalomyelitis])]). relacion([sujeto(['Resident', 'CNS', cells, are, believed, to, be, the, source, of, the, 'IL-4,', because, mice, deficient, in, 'T', cells, '(', 'SCID', and, 'RAG2-/-)']), verbo([expressed]), complemento([the, 'IL-4', gene, in, the, 'CNS'])]). relacion([sujeto(['Since', 'GATA-3-deficient', mice]), verbo([have]), complemento([an, abnormal, 'CNS,', 'brain-derived', 'Th2', cytokines, may, play, an, important, role, in, 'CNS', 'development,', as, well, as, potentially, contribute, to, the, 'immune-privileged', nature, of, the, brain])]). relacion([sujeto(['GATA-3', is, a, novel, transcription, factor, recently, shown, to]), verbo([regulate]), complemento(['IL-5', 'and,', 'possibly,', 'IL-4', gene, expression])]). relacion([sujeto(['We', previously]), verbo([reported]), complemento([that, 'GATA-3', is, increased, within, the, bronchial, mucosa, of, allergic, asthmatic, subjects, compared, with, control, subjects])]). relacion([sujeto(['In', the, present, study, we, set, out, to, determine, whether, there, is, also, an]), verbo([increased]), complemento([number, of, cells, expressing, 'GATA-3', messenger, '(', 'm)RNA', within, the, nasal, mucosa, of, patients, with, allergic, rhinitis])]). relacion([sujeto(['To', assess, the, contribution, of, resident, cells]), verbo([expressing]), complemento(['GATA-3', 'mRNA,', we, also, performed, isolated, explant, studies, in, which, nasal, mucosal, tissue, from, subjects, with, allergic, rhinitis, and, nonatopic, control, subjects, was, cultured, in, 'allergen-treated', medium])]). relacion([sujeto(['The', number, of, 'GATA-3', 'mRNA(+)', cells, was]), verbo([increased]), complemento([after, local, allergen, provocation, in, vivo, '(', increase, in, 'GATA-3', 'mRNA(+)', cells, '[', mean, +, /, -, 'SEM]:', subjects, with, allergic, 'rhinitis,', 11.3, +, /, -, 8.7, ;, control, 'subjects,', 1.2, +, /, -, 4.1, ;, 'P', &, 'lt;'])]). relacion([sujeto(['In', 'summary,', the, expression, of, the, transcription, factor, 'GATA-3', was]), verbo([increased]), complemento([after, allergen, 'challenge,', and, this, was, evident, in, the, absence, of, de, novo, inflammatory, cell, recruitment])]). relacion([sujeto(['GATA-3', may, be, a, potential]), verbo([target]), complemento([in, the, treatment, of, allergic, 'diseases,', such, as, rhinitis])]). relacion([sujeto(['Recombination']), verbo([activating]), complemento(['gene-1', '(', 'RAG-1)', and, 'RAG-2', are, expressed, in, lymphoid, cells, undergoing, the, antigen, receptor, gene, rearrangement])]). relacion([sujeto(['A', study, of, the, regulation, of, the, mouse, 'RAG-2', promoter, showed, that, the, 'lymphocyte-specific', promoter, activity, is]), verbo([conferred]), complemento([80, nucleotide, '(', 'nt)', upstream, of, 'RAG-2'])]). relacion([sujeto(['Using', an, electrophoretic, mobility, shift, 'assay,', it, was, shown, that, a, 'B-cell-specific', transcription, 'protein,', 'Pax-5,', and, a, 'T-cell-specific', transcription, 'protein,', 'GATA-3,']), verbo([bind]), complemento([to, the, -, 80, to, -, 17, nt, region, in, 'B', cells, and, 'T', 'cells,', respectively])]). relacion([sujeto(['These', results, indicate, that, distinct, 'DNA']), verbo([binding]), complemento(['proteins,', 'Pax-5', and, 'GATA-3,', may, regulate, the, murine, 'RAG-2', promoter, in, 'B', and, 'T', lineage, 'cells,', respectively])]). relacion([sujeto([3, ')', in, 'Gata3-/-', 'mice,', we, hypothesized, that, a, neuroendocrine, deficiency, in, the, sympathetic, nervous, system, '(', 'SNS)', might]), verbo([cause]), complemento([embryonic, lethality, in, these, mutants])]). relacion([sujeto(['We']), verbo([find]), complemento([here, that, null, mutation, of, 'Gata3', leads, to, reduced, accumulation, of, 'Th', '(', encoding, tyrosine, 'hydroxylase,', 'Th)', and, 'Dbh', '(', dopamine, 'beta-hydroxylase,', 'Dbh)', 'mRNA,', whereas, several, other, 'SNS', genes, are, unaffected])]). relacion([sujeto(['We', show, that, 'Th', and, 'Dbh', deficiencies]), verbo([lead]), complemento([to, reduced, noradrenaline, in, the, 'SNS,', and, that, noradrenaline, deficiency, is, a, proximal, cause, of, death, in, mutants, by, feeding, catechol, intermediates, to, pregnant, 'dams,', thereby, partially, averting, 'Gata3', 'mutation-induced', lethality])]). relacion([sujeto(['Thus', we]), verbo([have]), complemento([shown, that, 'Gata3', has, a, role, in, the, differentiation, of, multiple, cell, lineages, during, embryogenesis])]). relacion([sujeto(['GATA3', is, a, specific, 'T-cell', transcription, factor]), verbo([involved]), complemento([in, the, expression, of, 'T-cell', receptor, '(', 'TCR)'])]). relacion([sujeto(['In', order, to, characterize, the, relationship, between, 'HTLV-1', 'infection,', which]), verbo([has]), complemento([been, reported, to, be, associated, with, 'down-regulation', of, genes, belonging, to, the, 'TCR/CD3', 'complex,', and, the, transcription, factor, 'GATA3,', we, 'evaluated,', by, 'semi-quantitative', 'RT-PCR,', the, expression, of, 'GATA3', gene, in, 'HTLV-1', carriers, and, individuals, with, related, diseases])]). relacion([sujeto(['The', study, included, 4, asymptomatic, 'carriers,', 2, patients, with, adult, 'T-cell', 'leukaemia/lymphoma', '(', 'ATLL),', 1, patient, with, 'HTLV-1']), verbo([associated]), complemento([myelopathy, '(', 'HAM)/tropical', spastic, paraparesis, '(', 'TSP)', and, 7, healthy, blood, donors])]). relacion([sujeto(['A', considerable]), verbo([decrease]), complemento([in, the, expression, of, the, 'GATA3', mRNA, was, observed, in, all, subjects, infected, by, 'HTLV-1', and, no, expression, of, 'GATA3', mRNA, was, observed, in, 1, subject, with, 'ATLL', and, in, 1, with, 'HAM/TSP'])]). relacion([sujeto(['Gamma', delta, 'T', cells, secrete, 'Th1-', and, 'Th2-like', cytokines, that, help]), verbo([mediate]), complemento([innate, and, acquired, immunity])]). relacion([sujeto(['We']), verbo([have]), complemento([addressed, the, mechanism, whereby, murine, gamma, delta, 'T', cells, acquire, the, capacity, to, differentially, produce, such, cytokines])]). relacion([sujeto(['Splenic', gamma, delta, 'T', cells, could, be, polarized, into, 'IFN-gamma-', or, 'IL-4-secreting', cells, in, 'vitro;', 'however,', in, contrast, to, 'CD4+', alpha, beta, 'T', 'cells,', gamma, delta, 'T', cells, predominantly, produced, 'IFN-gamma,', even, in, the, presence, of, 'IL-4,', a]), verbo([finding]), complemento([independent, of, genetic, background])]). relacion([sujeto(['Like', 'CD4+', 'Th1', 'cells,', 'IFN-gamma-producing', cells]), verbo([expressed]), complemento([the, 'IL-12', receptor, beta, 2, -, chain, after, activation, in, the, presence, of, 'IL-12;', 'however,', unlike, 'Th2', 'cells,', 'IL-4-primed', gamma, delta, 'T', cells, also, expressed, this, 'receptor,', even, in, the, absence, of, 'IFN-gamma', and, despite, the, presence, of, the, transcription, factor, 'GATA-3'])]). relacion([sujeto(['IL-12', also]), verbo([induced]), complemento(['IL-4-primed', gamma, delta, 'T', cells, to, proliferate, and, to, translocate, 'Stat3/Stat4,', indicating, signaling, through, the, 'IL-12', receptor])]). relacion([sujeto(['We']), verbo([found]), complemento([the, reduced, level, of, 'IL-4', production, in, 'Stat6-deficient', 'T', cells, to, be, significantly, higher, than, in, 'Th1', controls])]). relacion([sujeto(['Using', a, novel, cell, surface, affinity, matrix, 'technique,', we]), verbo([found]), complemento([that, 'IL-4-secreting', 'Stat6-deficient', 'T', cells, stably, expressed, 'GATA-3', and, 'Th2', phenotype])]). relacion([sujeto(['Introducing', 'GATA-3', into, 'Stat6-deficient', 'T', cells, completely, restored, 'Th2', 'development,']), verbo([inducing]), complemento(['c-Maf,', 'Th2-specific', 'DNase', 'I', hypersensitive, sites, in, the, 'IL-4', 'locus,', and, 'Th2', cytokine, expression])]). relacion([sujeto(['To', further, understand, the, mechanisms]), verbo([involved]), complemento([in, the, generation, of, definitive, hemopoietic, stem, 'cells,', we, analysed, the, expression, of, the, 'hemopoietic-related', transcription, factors, 'Lmo2', and, 'GATA-3', during, the, early, steps, of, mouse, development, '(', 7, -, 12, 'dpc),', with, a, particular, emphasis, on, intraembryonic, hemogenic, sites])]). relacion([sujeto(['We', show, here, that, both, 'Lmo2', and, 'GATA-3', are, present, in, the, intraembryonic, regions, known, to, give, rise, to, hemopoietic, precursors, in, vitro, and, in, 'vivo,']), verbo([suggesting]), complemento([that, they, act, together, at, key, points, of, hemopoietic, development])]). relacion([sujeto(['(', 1, ')', 'Lmo2', and, 'GATA-3', are]), verbo([expressed]), complemento([in, the, caudal, mesoderm, during, the, phase, of, intraembryonic, precursors, determination])]). relacion([sujeto(['(', 2, ')', 'A', highly, transient, concomitant, expression, is, observed, in, the, caudal, intraembryonic, definitive, 'endoderm,']), verbo([suggesting]), complemento([that, these, factors, are, involved, in, the, specification, of, intraembryonic, hemopoietic, precursors])]). relacion([sujeto(['(', 3, ')', 'Lmo2', and, 'GATA-3', are]), verbo([expressed]), complemento([within, the, hemopoietic, clusters, located, in, the, aortic, floor, during, fetal, liver, colonisation])]). relacion([sujeto(['A', combined, in, situ, and, immunocytological, analysis, strongly]), verbo([suggests]), complemento([that, ventral, mesodermal, 'GATA-3', patches, are, involved, in, the, process, of, intraembryonic, stem, cell, generation])]). relacion([sujeto(['Here', we, constructed, 'Stat6:ER,', a, 'Stat6-estrogen', receptor, fusion, protein, that, can, be]), verbo([activated]), complemento([by, 4, -, 'hydroxy-tamoxifen,', independently, of, 'IL-4', and, endogenous, 'Stat6'])]). relacion([sujeto(['Retrovirus-mediated', introduction, of, 'Stat6:ER', into, developing, 'Th1', cells]), verbo([induced]), complemento(['Th2-specific', cytokines, and, suppressed, 'IFNgamma', production, in, a, 4, -, 'HT-dependent', manner, and, in, the, absence, of, 'IL-4'])]). relacion([sujeto(['It', also]), verbo([induced]), complemento(['GATA-3', and, 'c-maf', expression, and, downregulated, 'IL-12Rbeta2', chain, expression])]). relacion([sujeto(['Its']), verbo([decreased]), complemento([ability, to, induce, the, 'Th2', phenotype, with, progressing, 'Th1', cell, commitment, correlated, with, a, decreased, induction, of, 'GATA-3', and, 'c-maf'])]). relacion([sujeto(['This', study, indicates, that, 'Stat6', functions, upstream, of, 'GATA-3', and, 'c-Maf', to]), verbo([induce]), complemento(['Th2', development])]). relacion([sujeto(['We']), verbo([have]), complemento([used, a, conventional, and, a, mitogenic, 'CD28-specific', monoclonal, antibody, to, assess, the, effect, of, polyclonal, 'T', cell, activation, through, 'CD28', alone, on, 'CD4', subset, differentiation])]). relacion([sujeto(['In', 'vivo,', mitogenic, but, not, conventional, 'anti-CD28']), verbo([induces]), complemento([massive, 'lymphocytosis,', the, 'Th2', cytokines, interleukin, '(', 'IL)-4', and, 'IL-10,', and, 'Th2-dependent', immunoglobulin, 'isotypes,', most, notably, 'IgE'])]). relacion([sujeto(['At', the, molecular, 'level,', we, show, for, the, first, time, that, the, activation, of, the, &, 'quot;Th2', 'promoting"', transcription, factor, 'GATA-3']), verbo([requires]), complemento(['co-stimulation', by, 'CD28', and, is, also, induced, by, mitogenic, 'anti-CD28', alone])]). relacion([sujeto(['We']), verbo([suggest]), complemento([that, 'CD28-dependent', induction, of, 'GATA-3', in, concert, with, other, transcription, 'factors,', which, are, preferentially, induced, by, strong, 'CD28-signals,', primes, 'CD4', 'T', cells, for, 'IL-4-dependent', 'Th2', differentiaton])]). relacion([sujeto(['In', this, 'paper,', we, show, that, the, transcription, factor, 'GATA3', is, dynamically]), verbo([expressed]), complemento([during, hindbrain, development])]). relacion([sujeto(['In', 'particular,', the, absence, of, 'Hoxb1', results, in, the]), verbo([loss]), complemento([of, 'GATA2', expression, in, r4, and, the, absence, of, 'GATA2', results, in, the, loss, of, 'GATA3', expression])]). relacion([sujeto(['The', lack, of, 'GATA3', expression, in, r4]), verbo([inhibits]), complemento([the, projection, of, contralateral, vestibuloacoustic, efferent, neurons, and, the, migration, of, facial, branchiomotor, neurons, similar, to, 'Hoxb1-deficient', mice])]). relacion([sujeto(['Ubiquitous', expression, of, 'Hoxb1', in, the, hindbrain]), verbo([induces]), complemento([ectopic, expression, of, 'GATA2', and, 'GATA3', in, ventral, r2, and, r3])]). relacion([sujeto(['These', findings, demonstrate, that, 'GATA2', and, 'GATA3', lie, downstream, of, 'Hoxb1', and]), verbo([provide]), complemento([the, first, example, of, 'Hox', pathway, transcription, factors, within, a, defined, population, of, vertebrate, motor, neurons])]). relacion([sujeto(['The', cytokines, 'IL-4,', 'IL-5,', and, 'IL-13,', secreted, by, 'Th2', 'cells,']), verbo([have]), complemento([distinct, functions, in, the, pathogenesis, of, asthma])]). relacion([sujeto(['We']), verbo([have]), complemento([previously, shown, that, the, transcription, factor, 'GATA-3', is, expressed, in, 'Th2', but, not, 'Th1', cells])]). relacion([sujeto(['Expression', of, a, 'dominant-negative', mutant, of, 'GATA-3', in, mice, in, a, 'T', 'cell-specific', fashion]), verbo([led]), complemento([to, a, reduction, in, the, levels, of, all, the, 'Th2', cytokines, 'IL-4,', 'IL-5,', and, 'IL-13'])]). relacion([sujeto(['Thus,']), verbo([targeting]), complemento(['GATA-3', activity, alone, is, sufficient, to, blunt, 'Th2', responses, in, 'vivo,', thereby, establishing, 'GATA-3', as, a, potential, therapeutic, target, in, the, treatment, of, asthma, and, allergic, diseases])]). relacion([sujeto(['Here', we, describe, the, first, 'real-time', study, of]), verbo([nuclear]), complemento([protein, interaction, with, a, composite, 'DNA', regulatory, region])]). relacion([sujeto(['We', studied, the, interplay, between, the, three]), verbo([target]), complemento([sites, of, the, negative, regulatory, element, '(', 'NRE)', of, 'HIV-1', 'LTR,', comprising, a, noncanonical, 'GATA', site, overlapping, two, negative, regulatory, 'regions,', 'USF', and, 'NFIL-6,', and, their, corresponding, transcription, factors, in, nuclear, extracts])]). relacion([sujeto(['By', bandshift, 'analysis,', no, 'GATA']), verbo([binding]), complemento([activity, could, be, detected, between, 'LTR', 'NRE', and, different, nuclear, 'extracts,', although, evidenced, by, in, vitro, footprinting])]). relacion([sujeto(['BIAcore', study, of, these, interactions, revealed, the]), verbo([binding]), complemento([of, 'huGATA-3,', as, well, as, 'USF,', to, the, immobilized, 'LTR', 'NRE', oligonucleotide])]). relacion([sujeto(['Competition', 'analyses,', performed, with, 'GATA,', 'USF,', and, 'NFIL-6', 'oligonucleotides,', clearly, showed, that, this, regulatory, region, could]), verbo([bind]), complemento([both, 'huGATA-3', and, 'USF', factors])]). relacion([sujeto(['We']), verbo([have]), complemento([investigated, in, detail, the, expression, patterns, of, two, 'Gata', 'genes,', cGata2, and, 'cGata3,', during, early, chick, development])]). relacion([sujeto(['In', addition, to, confirming, previously, described, expression, of, these, two, genes, in, developing, 'brain,', kidney, and, blood, 'islands,', this, study]), verbo([reveals]), complemento([several, important, novel, expression, domains, during, very, early, stages, of, development])]). relacion([sujeto([cGata2, is]), verbo([expressed]), complemento([in, the, area, opaca, in, 'pre-primitive', streak, 'stages,', forming, a, gradient, along, the, 'A-P', axis, '(', strongest, 'anteriorly)'])]). relacion([sujeto(['Both', genes, are]), verbo([expressed]), complemento([strongly, in, the, entire, 'non-neural', ectoderm, from, stage, 4, +, ',', and, neither, is, expressed, in, prospective, neural, plate, at, any, stage])]). relacion([sujeto(['Unlike', other, previously, described, 'non-neural', 'markers,', neither, gene, is]), verbo([expressed]), complemento([in, the, dorsal, neural, tube])]). relacion([sujeto(['GATA3', is, a, transcription, factor]), verbo([expressed]), complemento([in, the, inner, ear, during, the, early, stages, of, development])]). relacion([sujeto(['A', monoclonal, antibody, revealed, that, it, is]), verbo([expressed]), complemento([in, spiral, ganglion, cells, and, in, all, cells, of, the, developing, auditory, sensory, epithelium, in, the, mouse, before, the, hair, cells, differentiate, at, embryonic, days, 14, -, 16])]). relacion([sujeto(['Expression']), verbo([decreases]), complemento([selectively, in, the, hair, cells, as, they, differentiate, progressively, from, the, base, to, the, apex, of, the, developing, organ, of, 'Corti'])]). relacion([sujeto(['GATA3', subsequently]), verbo([decreases]), complemento([in, the, supporting, cells, and, cannot, be, detected, by, immunofluorescence, in, any, cell, of, the, adult, sensory, epithelium])]). relacion([sujeto(['It', is, not]), verbo([expressed]), complemento([in, the, vestibular, sensory, epithelia, or, surrounding, tissues, from, embryonic, day, 14])]). relacion([sujeto(['We']), verbo([suggest]), complemento([that, 'GATA3', could, act, as, a, repressor, of, critical, genes, involved, in, cell, differentiation, in, the, organ, of, 'Corti,', enabling, a, progressive, formation, of, the, adult, cellular, pattern])]). relacion([sujeto(['Analysis', of, gene, expression, on, a, 'medium-', or, 'large-scale', is, an, increasingly]), verbo([recognized]), complemento([method, for, functional, and, clinical, investigations, based, on, the, now, extensive, catalog, of, known, or, partially, sequenced, genes])]). relacion([sujeto(['The', accessibility, of, this, approach, can, be]), verbo([enhanced]), complemento([by, using, readily, available, technology, '(', macroarrays, on, 'Nylon,', radioactive, 'detection)', and, the, 'IMAGE', resource, to, assemble, sets, of, targets])]). relacion([sujeto(['We']), verbo([have]), complemento([set, up, such, a, 'medium-scale,', flexible, system, and, validated, it, by, the, study, of, quantitative, expression, levels, for, 120, genes, in, six, cell, 'lines,', including, three, mammary, carcinoma, cell, lines])]). relacion([sujeto(['The', extensive, data, assembled, in, this, survey, identified, potential]), verbo([targets]), complemento([of, 'carcinogenesis,', for, example, the, 'CRABP2', and, 'GATA3', transcription, factor, genes])]). relacion([sujeto(['To', quantify, 'GATA-3', expression, during, 'T', cell, development, in, vivo, in, the, 'mouse,', the, 'GATA-3', gene, was]), verbo([targeted]), complemento([by, insertion, of, a, lacZ, reporter, by, homologous, recombination, in, embryonic, stem, '(', 'ES)', cells])]). relacion([sujeto(['The', two, periods, of, 'TCR', alpha, and, beta, gene, 'recombination,', which, occur, in, quiescent, or, slowly, dividing, 'cells,', were]), verbo([associated]), complemento([with, low, proportions, of, 'GATA-3+', cells])]). relacion([sujeto(['We', therefore, propose, that, 'GATA-3', is]), verbo([required]), complemento([for, the, expansion, of, 'T', cell, 'progenitors,', and, for, the, control, of, subsequent, proliferation, 'steps,', which, alternate, periods, of, 'TCR', recombination, in, the, thymus])]). relacion([sujeto(['We', demonstrate, that, virtually, all, neurons, in, the, caudal, raphe, nuclei, that]), verbo([express]), complemento(['GATA-3', also, produce, serotonin])]). relacion([sujeto(['The', development, and, function, of, 'T', lymphocytes, are]), verbo([regulated]), complemento([tightly, by, signal, transduction, pathways, that, include, specific, 'cell-surface', 'receptors,', intracellular, signaling, 'molecules,', and, nuclear, transcription, factors])]). relacion([sujeto(['Since', 1988, ',', several, families, of, functionally, important, 'T', cell, transcription, factors]), verbo([have]), complemento([been, identified])]). relacion([sujeto(['In', this, 'review,', we, summarize, our, current, understanding, of, the, transcriptional, regulation, of, 'T', cell, development, and, function, with, particular, emphasis, on, the, results, of, recent, gene]), verbo([targeting]), complemento([and, transgenic, experiments])]). relacion([sujeto(['In', addition, to]), verbo([increasing]), complemento([our, understanding, of, the, molecular, pathways, that, regulate, 'T', cell, development, and, 'function,', these, results, have, suggested, novel, targets, for, genetic, and, pharmacological, manipulation, of, 'T', cell, immunity])]). relacion([sujeto(['GATA-2', is]), verbo([expressed]), complemento([as, early, as, 9, dpc, in, the, 'hindbrain,', in, ventral, rhombomere, 4, ',', and, transiently, in, ventral, rhombomere, 2, '(', 'r2)'])]). relacion([sujeto(['GATA-3', is]), verbo([expressed]), complemento([in, a, pattern, very, similar, to, that, of, 'GATA-2'])]). relacion([sujeto(['In', 'addition,', 'GATA-2', is]), verbo([activated]), complemento([in, both, the, ventricular, and, the, subventricular, zones, of, the, neural, 'tube,', whereas, 'GATA-3', is, restricted, mainly, to, the, subventricular, zone])]). relacion([sujeto([5, and, 10.5, dpc, established, 'that:', '(', 'i)', the, expression, of, 'GATA-3', in, the, developing, 'CNS', of, the, mouse, embryo, is, dependent, on, the, presence, of, 'GATA-2', and, '(', 'ii)']), verbo([loss]), complemento([of, 'GATA-2', leads, to, severe, defects, in, 'neurogenesis,', which, strongly, suggests, that, 'GATA-2', is, 'involved,', as, in, 'hematopoiesis,', in, the, maintenance, of, the, pool, of, ventral, neuronal, progenitors])]). relacion([sujeto(['Thus,', it, is, unlikely, that, the, expression, of, effector, cytokines, is]), verbo([mediated]), complemento([solely, by, 'Stat', factors])]). relacion([sujeto(['Recently', there]), verbo([have]), complemento([been, indications, that, link, other, molecular, factors, to, 'Th', subset, development])]). relacion([sujeto(['The', transcription, factor, 'GATA-3', is, selectively]), verbo([expressed]), complemento([in, 'Th2', cells, and, has, been, shown, to, induce, the, expression, of, 'Th2', cytokines, in, developing, 'Th1', cells])]). relacion([sujeto(['We', now, show, that, ectopic, expression, of, 'GATA-3', in, developing, 'Th1', cells, significantly]), verbo([inhibits]), complemento(['IFN-gamma,', as, well, as, enhancing, 'IL-4', and, 'IL-5', production])]). relacion([sujeto(['Furthermore,', 'GATA-3']), verbo([inhibits]), complemento([production, of, 'IFN-gamma', by, developing, 'Th1', cells, in, the, complete, absence, of, 'IL-4'])]). relacion([sujeto(['Interleukin-5', '(', 'IL-5),']), verbo([expressed]), complemento([primarily, by, 'type-2', 'T', helper, '(', 'Th2)', 'cells,', plays, an, important, role, in, the, development, of, allergic, 'diseases,', such, as, allergic, asthma])]). relacion([sujeto(['Studying', the, regulation, of, 'IL-5', gene, expression, by, 'Ets', transcription, 'factors,', we]), verbo([found]), complemento([that, 'Ets1', and, 'Ets2,', but, not, 'Elf-1,', were, able, to, activate, the, human, 'IL-5', promoter, in, 'Jurkat', 'T-cells'])]). relacion([sujeto(['This']), verbo([required]), complemento([the, presence, of, either, phorbol, 12, -, myristate, acetate, '(', 'PMA)', plus, ionomycin, or, 'PMA', plus, the, viral, protein, 'HTLV-I', 'Tax1'])]). relacion([sujeto(['In', myeloid, 'Kasumi', 'cells,', 'Ets1', and, 'Ets2', failed, to]), verbo([stimulate]), complemento(['IL-5', promoter, 'activity,', unless, the, 'T-cell', specific, transcription, factor, 'GATA3', was, added])]). relacion([sujeto(['Both', ionomycin, and, 'Tax1']), verbo([increased]), complemento([the, combined, effect, of, 'GATA3', with, 'Ets1', and, 'Ets2', in, the, presence, of, 'PMA'])]). relacion([sujeto(['To', better, understand, the, molecular, basis, for, the, 'hormone-responsive', phenotype, in, breast, 'cancer,', we]), verbo([have]), complemento([used, a, human, cDNA, array, to, compare, patterns, of, gene, expression, between, breast, carcinoma, cell, lines, discordant, for, estrogen, receptor, '(', 'ER)', expression])]). relacion([sujeto(['Protein', immunoprecipitation, and, gel, shift, analysis, confirmed, the, presence, of, functional, 'GATA-3', protein, in, 'MCF7', but, not, in, 'HBL-100']), verbo([nuclear]), complemento([extracts])]). relacion([sujeto(['Our', results, indicate, that, 'GATA-3,', in, association, with, 'ER,', is, likely, to]), verbo([regulate]), complemento([genes, critical, to, the, 'hormone-responsive', breast, cancer, phenotype])]). relacion([sujeto(['Comparing', patterns, of, gene, expression, in, cell, lines, and, tissues]), verbo([has]), complemento([important, applications, in, a, variety, of, biological, systems])]). relacion([sujeto(['In', this, study, we]), verbo([have]), complemento([examined, whether, the, emerging, technology, of, cDNA, microarrays, will, allow, a, high, throughput, analysis, of, expression, of, cDNA, clones, generated, by, suppression, subtractive, hybridization, '(', 'SSH)'])]). relacion([sujeto(['We', conclude, that, 'SSH', and, microarray, technology, can, be, successfully, applied, to, identify, differentially]), verbo([expressed]), complemento([genes])]). relacion([sujeto(['This', approach, allowed, the, identification, of, differentially]), verbo([expressed]), complemento([genes, without, the, need, to, obtain, previously, cloned, cDNAs])]). relacion([sujeto(['The', 'GATA-3', transcription, factor, is]), verbo([required]), complemento([for, development, of, the, 'T-cell', lineage, and, 'Th2', cytokine, gene, expression, in, 'CD4', 'T-cells'])]). relacion([sujeto(['We']), verbo([have]), complemento([mapped, the, 'DNase-I-hypersensitive', '(', 'HS)', regions, of, the, human, 'GATA-3', gene, in, 'T-cells', and, 'non-T-cells', and, studied, their, transcriptional, activities])]). relacion([sujeto(['HS', 'I-III,', located, 5, '\'', from, the, transcriptional, initiation, 'site,', were]), verbo([found]), complemento([in, hematopoietic, and, 'non-hematopoietic', 'cells,', whereas, 'HS', 'IV-VII,', located, 3, '\'', from, the, transcriptional, start, 'site,', were, exclusively, observed, in, 'T-cells'])]). relacion([sujeto(['The', first, intron]), verbo([acted]), complemento([as, a, strong, transcriptional, activator, in, a, 'position-dependent', manner, and, with, no, 'cell-type', specificity])]). relacion([sujeto(['The', upstream, regulatory, element, could]), verbo([confer]), complemento(['T-cell', specificity, to, the, 'GATA-3', promoter, 'activity,', and, analysis, of, this, region, revealed, a, 707, -, base, pair, silencer, that, drastically, inhibited, 'GATA-3', promoter, activity, in, 'non-T-cells'])]). relacion([sujeto(['The', 3, '\'', -, 'CAGGTG', 'E-box', could]), verbo([bind]), complemento(['USF', 'proteins,', the, ubiquitous, repressor, 'ZEB,', or, the, basic, 'helix-loop-helix', proteins, 'E2A', and, 'HEB,', and, we, showed, that, a, competition, between, 'ZEB', and, 'E2A/HEB', proteins, is, involved, in, the, silencer, activity])]). relacion([sujeto(['High', expression, of, 'IL-5', by, 'T', cells, in, the, airways, of, asthmatic, individuals, is, believed, to, play, a, fundamental, role, in, the, eosinophilia]), verbo([associated]), complemento([with, this, disease])]). relacion([sujeto(['We']), verbo([report]), complemento([that, 'GATA-3', mRNA, expression, is, significantly, increased, in, the, airways, of, asthmatic, subjects, compared, with, those, of, normal, control, subjects, '(', 'P', &, 'lt;'])]). relacion([sujeto(['Numbers', of, cells]), verbo([expressing]), complemento(['GATA-3', transcripts, correlated, significantly, with, reduced, airway, caliber, '(', 'P', &, 'lt;'])]). relacion([sujeto(['The', density, of, 'GATA-3', 'mRNA+', cells, correlated, significantly, with, the, numbers, of, cells]), verbo([expressing]), complemento(['IL-5', mRNA, '(', 'P', &, 'lt;'])]). relacion([sujeto(['The', results, of, this, study]), verbo([provide]), complemento([the, first, evidence, of, increased, 'GATA-3', gene, expression, in, association, with, 'IL-5', 'mRNA+', cells, in, asthmatic, airways])]). relacion([sujeto(['We']), verbo([found]), complemento([previously, that, neither, a, 6, -, kbp, promoter, fragment, nor, even, a, 120, -, kbp, yeast, artificial, chromosome, '(', 'YAC)', containing, the, whole, 'GATA-3', gene, was, sufficient, to, recapitulate, its, full, transcription, pattern, during, embryonic, development, in, transgenic, mice])]). relacion([sujeto(['In', an, attempt, to, further, identify, 'tissue-specific', regulatory, elements]), verbo([modulating]), complemento([the, dynamic, embryonic, pattern, of, the, 'GATA-3', 'gene,', we, have, examined, the, expression, of, two, much, larger, '(', 540, -, and, 625, -, 'kbp)', 'GATA-3', 'YACs', in, transgenic, animals])]). relacion([sujeto(['We']), verbo([found]), complemento([that, most, of, the, 'YAC', expression, sites, and, tissues, are, directly, reflective, of, the, endogenous, 'pattern,', and, detailed, examination, of, the, integrated, 'YAC', transgenes, allowed, the, general, localization, of, a, number, of, very, distant, transcriptional, regulatory, elements, '(', putative, central, nervous, 'system-,', 'endocardium-,', and, urogenital, 'system-specific', 'enhancers)'])]). relacion([sujeto(['Remarkably,', even, the, 625, -, kbp, 'GATA-3', 'YAC,', containing, approximately, 450, kbp, and, 150, kbp, of, 5, '\'', and, 3, '\'', flanking, 'sequences,', 'respectively,', does, not, contain, the, full, transcriptional, regulatory, potential, of, the, endogenous, locus, and, is, clearly, missing, regulatory, elements, that]), verbo([confer]), complemento(['tissue-specific', expression, to, 'GATA-3', in, a, subset, of, neural, 'crest-derived', cell, lineages])]). relacion([sujeto(['GATA-3', is, essential, for, murine, embryonic, 'development,', but, elucidating, the, genetic, controls, over, the, complex, temporal, and, 'tissue-specific', transcriptional, regulatory, pattern, of, this, transcription, factor, gene]), verbo([has]), complemento([been, problematic])]). relacion([sujeto(['Here', we]), verbo([report]), complemento([the, isolation, and, characterization, of, two, yeast, artificial, chromosomes, '(', 'YACs)', bearing, the, murine, 'GATA-3', gene])]). relacion([sujeto(['We']), verbo([found]), complemento([that, a, 120, -, kb, 'YAC', 'transgene,', including, 35, kb, of, 5, '\'', as, well, as, 60, kb, of, 3, '\'', flanking, 'sequence,', confers, normal, 'GATA-3', expression, at, sites, not, revealed, previously, through, analysis, of, plasmid, transgenic, lines])]). relacion([sujeto(['While', 'EKLF', is]), verbo([expressed]), complemento([exclusively, in, erythroid, 'cells,', 'LKLF', is, expressed, temporally, during, early, embryonic, development, and, predominantly, in, the, adult, mouse, lung])]). relacion([sujeto(['To', understand, the, role, this, novel, transcription, factor, plays, in, development, as, well, as, tissue, differentiation, and, 'function,', animals, lacking, 'LKLF', were, produced, using, gene]), verbo([targeting]), complemento([technology])]). relacion([sujeto(['These', findings, demonstrate, the, 'LKLF', function, is, indispensable, during, normal, embryonic, 'development,', and, although, both, 'LKLF', and, 'EKLF']), verbo([recognize]), complemento([common, 'DNA', 'motifs,', they, do, not, substitute, for, each, other])]). relacion([sujeto(['Recently,', the, transcription, factor, 'GATA-3', was, shown, to, be, selectively]), verbo([expressed]), complemento([in, 'Th2', but, not, 'Th1', cells, and, to, augment, 'Th2-specific', cytokines])]). relacion([sujeto(['Here,', we, show, that]), verbo([loss]), complemento([of, 'GATA-3', expression, by, developing, 'Th1', cells, requires, 'IL-12', signaling, through, 'Stat4', and, does, not, simply, result, from, an, absence, of, 'IL-4'])]). relacion([sujeto(['GATA-3']), verbo([inhibits]), complemento(['Th1', cytokines, by, a, 'cell-intrinsic', mechanism, that, is, not, dependent, on, 'IL-4', and, that, may, involve, repression, of, 'IL-12', signaling])]). relacion([sujeto(['We', screened, a, panel, of, 1, ',', 920, randomly, selected, cDNAs, to, discover, genes, that, are, differentially]), verbo([expressed]), complemento([in, 'HL60', cells, exposed, to, 60, 'Hz', magnetic, fields, '(', 2, 'mT)', or, 'X', rays, '(', 5, 'Gy)', compared, to, unexposed, cells])]). relacion([sujeto(['Eighteen', cDNAs, differentially]), verbo([expressed]), complemento([in, 'X-irradiated', compared, to, control, 'HL60', cells, were, recovered, from, a, panel, of, 1, ',', 920, clones])]). relacion([sujeto(['Our', results]), verbo([suggest]), complemento([that, differential, gene, expression, is, induced, in, approximately, 1, '%', of, a, random, pool, of, cDNAs, by, ionizing, radiation, but, not, by, 60, 'Hz', magnetic, fields, under, the, present, experimental, conditions])]). relacion([sujeto(['Previously,', we]), verbo([have]), complemento([shown, that, 'TAL1', and, the, 'LIM-only', protein, gene, '(', 'LMO)', are, regularly, coactivated, in, 'T-cell', acute, lymphoblastic, leukemia, '(', 'T-ALL)'])]). relacion([sujeto(['To', understand, the, molecular, mechanisms, of, functional, synergy, between, 'TAL1', and, 'LMO', in, tumorigenesis, and, transcriptional, 'regulation,', we, tried, to, identify, downstream]), verbo([target]), complemento([genes, regulated, by, 'TAL1', and, 'LMO', by, a, subtractive, 'PCR', method])]). relacion([sujeto(['One', of, the, isolated, 'genes,', that, for, retinaldehyde, dehydrogenase, 2, '(', 'RALDH2),', was, regularly]), verbo([expressed]), complemento([in, most, of, the, 'T-ALL', cell, lines, that, coexpressed, 'TAL1', and, 'LMO'])]). relacion([sujeto(['Exogenously', transfected, 'TAL1', and, 'LMO,', but, not, either, 'alone,']), verbo([induced]), complemento(['RALDH2', expression, in, a, 'T-ALL', cell, 'line,', 'HPB-ALL,', not, expressing, endogeneous, 'TAL1', or, 'LMO'])]). relacion([sujeto(['Promoter', analysis, revealed, that, a, 'GATA', site, in, a, cryptic, promoter, in, the, second, intron, was, essential, and, sufficient, for, the, 'TAL1-', and, 'LMO-dependent', transcriptional, 'activation,', and, 'GATA3']), verbo([binds]), complemento([to, this, site])]). relacion([sujeto(['Furthermore,', a, 'TAL1', mutant, not]), verbo([binding]), complemento([to, 'DNA', also, activated, the, transcription, of, 'RALDH2', in, the, presence, of, 'LMO', and, 'GATA3'])]). relacion([sujeto(['Collectively,', we]), verbo([have]), complemento([identified, the, 'RALDH2', gene, as, a, first, example, of, direct, transcriptional, target, genes, regulated, by, 'TAL1', and, 'LMO', in, 'T-ALL'])]). relacion([sujeto(['In', this, 'case,', 'TAL1', and, 'LMO']), verbo([act]), complemento([as, cofactors, for, 'GATA3', to, activate, the, transcription, of, 'RALDH2'])]). relacion([sujeto(['To', study, the, regulatory, mechanism, of, gp91phox, gene, expression, in, 'eosinophils,', we, transiently, transfected, 'eosinophil-committed', 'HL-60-C15', cells, with, gp91phox, promoter, 'constructs,', and, identified, a, negative, element, from, bp, -, 267, to, -, 246, of, the, gp91phox, 'gene,', the, deletion, of, which]), verbo([caused]), complemento([an, 83, '%', increase, in, promoter, activity])]). relacion([sujeto(['Electrophoresis', mobility, shift, assays, demonstrated, 'GATA-3']), verbo([binds]), complemento([to, the, 'GATA', consensus, site, from, bp, -, 256, to, -, 250])]). relacion([sujeto(['An', 81, '%', increment, in, promoter, activity, was, obtained, when, a, mutation, was, introduced, in, the, 'GATA-3']), verbo([binding]), complemento([site, of, the, bp, -, 267, to, +, 12, 'construct,', which, is, comparable, to, that, of, the, bp, -, 245, to, +, 12, construct])]). relacion([sujeto(['We', therefore, conclude, that, 'GATA-3', specifically]), verbo([binding]), complemento([to, the, 'GATA', site, negatively, regulates, the, expression, of, the, gene, in, 'HL-60-C15', cells])]). relacion([sujeto(['Transgenic', mice, with, human, 'CD3epsilon', gene]), verbo([have]), complemento([been, shown, to, exhibit, early, arrest, of, 'T', cell, development, in, the, thymus])]). relacion([sujeto(['The', accumulation, of, mature, 'B', cells, in, the, thymus, was]), verbo([found]), complemento([only, in, tg, epsilon26, 'mice,', not, in, other, human, 'CD3epsilon', transgenic, mouse, lines, or, other, 'T', 'cell-deficient', 'mice,', including, 'CD3-epsilon', knockout, mice, and, 'TCR-beta/TCR-delta', double, knockout, mice])]). relacion([sujeto(['Interestingly,', tg, epsilon26, thymocytes]), verbo([expressed]), complemento(['GATA-3', and, 'TCF-1,', but, not, 'LEF-1', and, 'PEBP-2alpha,', among, 'T', 'cell-specific', transcription, factors, that, are, involved, in, early, 'T', cell, 'development,', indicating, that, 'GATA-3', and, 'TCF-1', expressed, during, thymocyte, development, do, not, necessarily, determine, the, cell, fate, into, 'T', cell, lineage])]). relacion([sujeto(['Thus,', tg, epsilon26, mice]), verbo([provide]), complemento([a, novel, mouse, model, in, that, lineage, choice, between, 'T', and, 'B', lymphocytes, is, genetically, defective])]). relacion([sujeto(['An', 800, -, base, pair, proximal, promoter]), verbo([conferred]), complemento([some, 'Th2-selective', expression, in, transgenic, mice])]). relacion([sujeto(['However,', this, region, directed, extremely, low, reporter, mRNA, levels, relative, to, endogenous, 'IL-4', 'mRNA,']), verbo([suggesting]), complemento([that, full, gene, activity, requires, additional, enhancer, elements])]). relacion([sujeto(['The', proximal, 'IL-4', promoter, is, only, moderately, augmented, by, 'GATA-3,', but, certain, genomic, regions, significantly]), verbo([enhanced]), complemento(['GATA-3', promoter, transactivation])]). relacion([sujeto(['Some']), verbo([enhancing]), complemento([regions, contained, 'consensus,', 'GATA', sites, that, bound, 'Th2-specific', complexes])]). relacion([sujeto(['However,', retroviral, transduction, of, 'GATA-3', into, developing, 'T', cells]), verbo([induced]), complemento(['IL-5', to, full, 'Th2', 'levels,', but, only, partially, restored, 'IL-4', production])]). relacion([sujeto(['Thus,', we, propose, that, 'GATA-3', is, 'permissive,', but, not, 'sufficient,', for, full, 'IL-4', enhancement, and, may]), verbo([act]), complemento([through, 'GATA', elements, surrounding, the, 'IL-13/IL-4', gene, locus])]). relacion([sujeto(['We']), verbo([have]), complemento([previously, shown, that, the, transcription, factor, 'GATA-3', is, expressed, in, 'Th2', but, not, 'Th1', cells, and, is, crucial, for, activation, of, the, 'IL-5', promoter, by, different, stimuli])]). relacion([sujeto(['Also,', in, 'Th2', 'cells,', antisense, 'GATA-3', 'RNA']), verbo([inhibits]), complemento(['IL-5', but, not, 'IL-4', promoter, activation])]). relacion([sujeto(['The', induction, of, 'IL-5', gene, expression, by, 'GATA-3']), verbo([involves]), complemento([high, affinity, binding, of, 'GATA-3', to, an, inverted, 'GATA', repeat, in, the, 'IL-5', promoter])]). relacion([sujeto(['Recent', studies, in, early, 'Xenopus', and, zebrafish, embryos]), verbo([have]), complemento([demonstrated, that, 'posteriorizing,', 'non-axial', signals, arising, from, outside, the, organizer, '(', or, 'shield)', contribute, to, 'A/P', patterning, of, the, neural, 'axis,', in, contradiction, to, the, classical, 'Spemann', model, in, which, such, signals, were, proposed, to, be, solely, organizer, derived])]). relacion([sujeto(['Thus', we]), verbo([find]), complemento([that, the, earliest, expression, of, 'GATA-2', and, 3, is, located, in, nonneural, ectoderm, and, is, strongly, patterned, in, a, graded, manner, along, the, 'A/P', 'axis,', being, high, anteriorly, and, absent, from, the, most, posterior, regions])]). relacion([sujeto(['These', regions, correspond, to, 'head,', trunk, and, tail, ectoderm, and, may, represent, the, beginnings, of, functional, segmentation, of, nonneural, 'ectoderm,', as]), verbo([suggested]), complemento([in, the, concept, of, the, '\'', 'ectomere\''])]). relacion([sujeto(['We']), verbo([find]), complemento([that, 'A/P', patterning, of, 'GATA', expression, in, nonneural, ectoderm, may, occur, as, early, as, late, 'blastula/early', gastrula, stages])]). relacion([sujeto(['We', investigate, which, posteriorizing, signals, might, contribute, to, such, distinct, non, axial, ectodermal, patterning, in, the, 'A/P', axis, and]), verbo([provide]), complemento([evidence, that, both, 'FGF', and, a, 'Wnt', family, member, contribute, towards, the, final, 'A/P', pattern, of, 'GATA', expression, in, nonneural, ectoderm])]). relacion([sujeto(['The', 'tissue-', and, 'stage-specific', assembly, of, 'Ag', receptor, genes, is]), verbo([regulated]), complemento([by, transcriptional, control, elements, positioned, within, 'Ig', and, 'TCR', loci])]). relacion([sujeto(['To', further, understand, the, role, of, 'cis-acting', elements, in, these, regulatory, 'mechanisms,', we]), verbo([have]), complemento([characterized, a, transcriptional, promoter, that, drives, germline, expression, of, 'TCR', beta, gene, segments, in, vivo])]). relacion([sujeto(['The', activity, of, this, 'promoter,', termed, 'PD', 'beta,', is, restricted, to, a, highly]), verbo([conserved]), complemento([400, -, bp, region, located, directly, upstream, from, 'D', beta, 1, -, coding, sequences])]). relacion([sujeto(['Maximal', 'PD', beta, activity]), verbo([requires]), complemento([a, 'TATA', element, situated, within, the, 'D', beta, 1, recombination, signal, sequences, and, consensus, binding, sites, for, the, ubiquitous, 'SP1', and, the, 'T', 'cell-specific', 'GATA-3', transcription, factors])]). relacion([sujeto(['When', linked, to, active, enhancer, 'elements,', 'PD', beta, directs, transcription, in, most, cell, 'types;', 'however,', the, 'TCR', beta, enhancer, '(', 'E', 'beta)']), verbo([stimulates]), complemento(['PD', beta, function, specifically, in, precursor, 'T', lymphocytes])]). relacion([sujeto(['These', findings]), verbo([suggest]), complemento([that, 'PD', 'beta/E', beta, interactions, may, contribute, to, differential, regulation, of, regions, within, the, 'TCR', beta, locus, during, thymocyte, development])]). relacion([sujeto(['Recombination']), verbo([requires]), complemento([the, accessibility, of, substrate, gene, 'segments,', and, transcriptional, enhancers, and, promoters, have, been, shown, to, regulate, the, accessible, chromatin, configuration])]). relacion([sujeto(['Sequences']), verbo([required]), complemento([for, full, promoter, activity, were, identified, by, transient, transfections, of, normal, and, mutated, promoters, into, a, human, gammadelta, 'lymphoma,', and, necessary, elements, fall, between, -, 86, and, +, 66, 'nt,', relative, to, the, major, transcription, start, site])]). relacion([sujeto(['Gel', shift, analyses, and, in, vitro, 'DNase', 'I', footprinting, showed, that]), verbo([nuclear]), complemento([proteins, bind, to, the, functionally, relevant, 'CRE,', 'Ets,', +, 1, to, +, 10, 'sequence,', and, the, +, 17, to, +, 21, sequence])]). relacion([sujeto(['Nuclear', proteins, also]), verbo([bind]), complemento([to, an, 'E', box, at, -, 52, ',', and, 'GATA-3', binds, to, a, 'GATA', motif, at, -, 5, ',', as, shown, by, 'Ab', 'ablation-supershift', 'experiments,', but, mutations, that, abrogated, protein, binding, to, these, sites, failed, to, affect, 'DV101S1', promoter, activity])]). relacion([sujeto(['Allergens', and, infections, with, parasitic, helminths, preferentially]), verbo([induced]), complemento(['Th2', immune, responses, associated, with, elevated, levels, of, serum, immunoglobulin, 'E', '(', 'IgE)', and, expansion, of, eosinophils, and, mast, cells])]). relacion([sujeto(['Interleukin-4', '(', 'IL-4)', is, a, key, cytokine, in, the, differentiation, of, naive, 'CD4+', 'T', cells, into, 'Th2', 'cells,', which, produce, a, panel, of, cytokines, including, 'IL-4,', 'IL-5,', 'IL-6,', 'IL-9,', 'IL-10,', and, 'IL-13', '[', 1, ']', and]), verbo([have]), complemento([been, shown, to, trigger, recovery, from, gastrointestinal, nematodes, '[', 2, ']'])]). relacion([sujeto(['Nonetheless,', mice, deficient, for, 'IL-4']), verbo([have]), complemento([been, shown, to, develop, residual, 'Th2', responses, '[', 3, -, 5, ']', and, can, expel, the, nematode, 'Nippostrongylus', brasiliensis, '[', 6, ']', ',', suggesting, that, there, is, a, functional, equivalent, of, 'IL-4', in, these, processes])]). relacion([sujeto(['Unlike', 'IL-4,', 'IL-4R', alpha, was]), verbo([required]), complemento([for, control, of, 'N'])]). relacion([sujeto(['Injection', of, recombinant, 'IL-13']), verbo([induced]), complemento([worm, expulsion, in, otherwise, incompetent, 'RAG2-/-', mice])]). relacion([sujeto(['Our', results]), verbo([suggest]), complemento([that, 'IL-13', regulates, 'Th2', responses, to, nematode, infection, and, requires, 'IL-4R', alpha])]). relacion([sujeto(['Cas-Br-E', and, 'Graffi', are, two, murine, viruses, that]), verbo([induce]), complemento([myeloid, leukemia, in, 'mice:', while, 'Cas-Br-E', induces, mostly, 'non-T,', 'non-B', leukemia, composed, of, very, immature, 'cells,', 'Graffi', causes, exclusively, a, granulocytic, leukemia, '(', 'E'])]). relacion([sujeto(['In', an, attempt, to, understand, the, basis, of, the, myeloid, specificity, of, these, two, 'retroviruses,', we, used, 'DNase', 'I', footprinting, analysis, and, gel, mobility, shift, assays, to, identify, a, number, of, protein]), verbo([binding]), complemento([sites, within, the, 'Cas-Br-E', and, 'Graffi', 'U3', regions])]). relacion([sujeto(['Two', protected, regions, include, potential, 'GATA']), verbo([binding]), complemento([sites])]). relacion([sujeto(['Methylation', interference, analysis, with, different, hematopoietic]), verbo([nuclear]), complemento([extracts, showed, the, importance, of, the, 'G', residues, in, these, 'GATA', 'sites,', and, supershift, assays, clearly, identified, the, binding, factors, as, 'GATA-1,', 'GATA-2,', and, 'GATA-3'])]). relacion([sujeto(['GATA-1', is]), verbo([required]), complemento([for, differentiation, of, two, hematopoietic, lineages, '(', red, blood, cells, and, 'megakaryocytes),', whereas, 'GATA-3', is, essential, for, 'T-cell', development])]). relacion([sujeto(['Functional', studies]), verbo([suggest]), complemento([that, many, properties, of, the, 'GATA-family', of, proteins, are, shared, and, largely, interchangeable])]). relacion([sujeto(['Mutant', embryos, '(', designated, 'G1G3ki),', though, embryonic, 'lethal,', exhibit, partial, 'rescue,', characterized, by]), verbo([increased]), complemento([survival, of, erythroid, precursor, cells, and, improved, hemoglobin, production])]). relacion([sujeto(['Our', findings]), verbo([suggest]), complemento([that, 'GATA-3', protein, is, functional, when, expressed, in, an, erythroid, environment, and, is, competent, to, act, on, at, least, a, subset, of, 'erythroid-expressed', target, genes, in, vivo])]). relacion([sujeto(['Until', now, the, allantois]), verbo([has]), complemento([not, been, considered, as, a, hematopoietic, organ])]). relacion([sujeto(['Here', we]), verbo([report]), complemento([experimental, evidence, demonstrating, the, in, situ, emergence, of, both, hematopoietic, and, endothelial, precursors, in, the, avian, allantoic, bud])]). relacion([sujeto(['When', the, prevascularized, allantoic, bud, from, a, quail, embryo, was, grafted, in, the, coelom, of, a, chicken, 'host,', hematopoietic, and, endothelial, cells, later, were]), verbo([found]), complemento([in, the, bone, marrow, of, the, host])]). relacion([sujeto(['We', also, show, by, reverse, 'transcription-PCR', that, the, allantois, region]), verbo([expresses]), complemento([very, early, the, 'GATA', genes, involved, in, hematopoiesis, and, some, 'beta-globin', chain, genes])]). relacion([sujeto(['We']), verbo([have]), complemento([previously, defined, four, 'cis-regulatory', elements, of, the, 'IL-5', promoter, responding, to, 'PMA', and, cAMP, in, 'EL-4', cells])]). relacion([sujeto(['We', now]), verbo([report]), complemento([that, the, 1.2, -, kb, region, of, the, 'IL-5', promoter, directs, expression, of, the, 'IL-5', gene, in, a, 'Th2', clone, but, not, a, 'Th1', 'clone,', indicating, that, transcription, from, the, 'IL-5', promoter, is, 'Th2', specific])]). relacion([sujeto(['IL-5CLE0']), verbo([interacted]), complemento([with, both, constitutive, and, inducible, nuclear, factors, '(', designated, 'NFIL-5CLE0),', which, existed, in, both, 'Th1', and, 'Th2', 'clones,', whereas, 'IL-5C', interacted, with, a, constitutive, nuclear, factor, '(', designated, 'NFIL-5C),', which, was, found, only, in, 'Th2', but, not, in, 'Th1', clones])]). relacion([sujeto(['The', sequence, for, 'NFIL-5C']), verbo([binding]), complemento([bears, homology, with, 'GATA-binding', sites])]). relacion([sujeto(['The', 'NFIL-5C', complex, was, supershifted, by, an, 'anti-GATA-3', 'Ab', and]), verbo([inhibited]), complemento([by, an, oligonucleotide, containing, 'GATA-binding', sites])]). relacion([sujeto(['Finally,', we, demonstrated, that, in, 'vitro-translated', 'GATA-3']), verbo([bound]), complemento([to, 'IL-5C', and, overexpression, of, 'GATA-3', augmented, 'stimulation-dependent', 'IL-5', promoter, activity, in, 'EL-4', cells])]). relacion([sujeto(['Taken', 'together,', our, results]), verbo([provide]), complemento([evidence, that, 'GATA-related', factors, may, be, involved, in, 'Th2-specific', expression, of, the, 'IL-5', gene])]). relacion([sujeto(['Relative', affinities, of, transcriptional, regulatory, elements, for, their, respective, factor]), verbo([have]), complemento([been, essentially, studied, by, bandshift, analysis])]). relacion([sujeto(['Here', we]), verbo([report]), complemento([a, 'real-time', study, of, 'factor/DNA', interactions, using, a, surface, plasmon, resonance, approach, and, further, characterization, of, recovered, proteins, involved, in, this, interaction])]). relacion([sujeto(['For', this, 'purpose,', human, 'GATA-3,', either, recombinant, or, in]), verbo([nuclear]), complemento(['extracts,', and, three, natural, 'GATA', elements, of, the, 'HIV-1', long, terminal, repeat, '(', sites, 1, ',', 2, ',', and, 3, ')', were, 'chosen,', in, which, only, site, 2, is, a, noncanonical, 'GATA', site])]). relacion([sujeto(['Interactions', between, the, canonical, and, unique, 'GATA', site, 3, and]), verbo([nuclear]), complemento([extracts, were, also, studied, in, real, time, and, provided, information, on, its, association, and, dissociation, rates, for, native, 'huGATA-3'])]). relacion([sujeto(['Despite']), verbo([increasing]), complemento([evidence, that, the, outcome, of, many, diseases, is, determined, by, the, ratio, of, the, two, subsets, of, 'CD4(+)', 'T', helper, 'cells,', 'Th1', and, 'Th2,', the, molecular, basis, for, 'Th1-', and, 'Th2-specific', gene, expression, remains, to, be, elucidated])]). relacion([sujeto(['We', previously, established, a, critical, role, for, the, transcription, factor, 'GATA-3', in, 'IL-5', promoter, activation, in, 'EL-4', 'cells,', which]), verbo([express]), complemento([both, 'Th1-', and, 'Th2-type', cytokines])]). relacion([sujeto(['Our', studies]), verbo([reported]), complemento([here, demonstrate, that, 'GATA-3', is, critical, for, expression, of, the, 'IL-5', gene, in, bona, fide, 'Th2', cells])]). relacion([sujeto(['Whereas', mutations, in, the, 'GATA-3', site, abolished, 'antigen-', or, 'cAMP-stimulated', 'IL-5', promoter, activation, in, 'Th2', 'cells,', ectopic, expression, of, 'GATA-3', in, 'Th1', cells, or, in, a, 'non-lymphoid,', 'non-IL-5-producing', cell, line]), verbo([activated]), complemento([the, 'IL-5', promoter])]). relacion([sujeto(['During', the, differentiation, of, naive, 'CD4(+)', 'T', cells, isolated, from, 'T', cell, receptor, transgenic, 'mice,', 'GATA-3', gene, expression, was, 'up-regulated', in, developing, 'Th2', 'cells,', but, was, 'down-regulated', in, 'Th1', 'cells,', and, 'antigen-', or, 'cAMP-activated', 'Th2', cells, '(', but, not, 'Th1', 'cells)']), verbo([expressed]), complemento([the, 'GATA-3', protein])]). relacion([sujeto(['Inhibition', of, 'GATA-3', activity]), verbo([has]), complemento([therapeutic, potential, in, the, treatment, of, asthma, and, other, hypereosinophilic, diseases])]). relacion([sujeto(['GATA-3', is]), verbo([expressed]), complemento([in, a, temporally, dynamic, manner, and, fulfills, vital, functions, during, vertebrate, fetal, development])]). relacion([sujeto(['Homozygous', 'mGATA-3', mutant, embryos, die, at, 'midgestation,', thus, complicating, the, analysis, of, its, contribution, to, the, development, of, specific, cell, fates, in, the, many, tissues, where, it, is]), verbo([expressed]), complemento([during, embryogenesis])]). relacion([sujeto(['We', show, here, that, the, elements, controlling, 'GATA-3', regulation, can, be, precisely, 'refined,', using, transgenic, 'mice,', to, discrete, 'cis-acting', 'domains:', within, 6, kb, surrounding, the, transcriptional, initiation, 'site,', separate, sequences, were]), verbo([found]), complemento([to, control, the, expression, of, 'mGATA-3', in, early, muscle, 'masses,', in, a, subset, of, 'PNS', 'neurons,', in, the, genital, 'tubercle,', and, in, the, branchial, arches])]). relacion([sujeto(['The', enhancer, contains, potential]), verbo([binding]), complemento([sites, for, many, 'well-characterized', transcription, 'factors,', suggesting, that, 'mGATA-3', transcriptional, activity, may, be, regulated, by, these, proteins, '(', or, related, family, 'members)', in, the, mesenchyme, of, the, arches, that, contribute, to, formation, of, the, jaw])]). relacion([sujeto(['These', studies, show, that, discrete, regulatory, elements]), verbo([required]), complemento([for, the, elaboration, of, complex, developmental, programs, can, be, individually, 'localized,', suggesting, that, the, developmentally, transient, expression, of, individual, transcription, factors, collaboratively, contributes, to, the, temporal, and, spatial, pattern, of, cellular, differentiation, leading, to, the, formation, of, adult, anatomy])]). relacion([sujeto(['In', the, present, 'studies,', we]), verbo([have]), complemento([characterized, three, regulatory, elements, in, the, proximal, 5, '\'', -, flanking, regions, of, the, 'gene,', using, electrophoretic, mobility, shift, assays, and, reporter, gene, analysis])]). relacion([sujeto(['First,']), verbo([nuclear]), complemento([factors, recognized, by, antibodies, against, 'Sp1', and, 'Sp3', were, found, to, bind, the, 'Sp1', motif, in, the, region, from, -, 52, to, -, 43])]). relacion([sujeto(['Mutation', of, the, 'Sp1-binding', site]), verbo([decreased]), complemento([the, promoter, activity, to, 30, '%', in, 'JEG-3', cells, and, to, 60, '%', in, 'JAR', 'cells,', suggesting, that, binding, to, the, 'Sp1', motif, has, a, substantial, role, in, the, complete, functioning, of, the, 'HSD17B1', promoter])]). relacion([sujeto(['Second,', the]), verbo([binding]), complemento([of, 'AP-2', to, its, motif, in, the, region, from, -, 62, to, -, 53, led, to, reduced, binding, of, 'Sp1', and, 'Sp3,', and, 'furthermore,', mutation, of, the, 'AP-2', element, increased, promoter, activity, to, 260, '%', in, 'JEG-3', cells])]). relacion([sujeto(['The', data, thus, implied, that, 'AP-2', can, repress, the, function, of, the, 'HSD17B1', promoter, by]), verbo([preventing]), complemento([binding, to, the, 'Sp1', motif])]). relacion([sujeto(['Finally,', 'GATA', 'factors,', 'GATA-3', in, 'particular,', were, demonstrated, to]), verbo([bind]), complemento([their, cognate, sequence, in, the, 'HSD17B1', silencer, 'region,', and, mutations, introduced, into, the, 'GATA-binding', site, increased, transcriptional, activity, to, the, level, seen, in, constructs, not, containing, the, silencer, element])]). relacion([sujeto(['Thus,', 'GATA-3', seems, to]), verbo([prevent]), complemento([transcription, in, the, 'constructs,', and, 'hence,', the, 'GATA', motif, also, may, operate, as, a, negative, control, element, for, 'HSD17B1', transcription])]). relacion([sujeto(['We']), verbo([found]), complemento([that, 'GATA-3', was, selectively, expressed, in, 'Th2', cells])]). relacion([sujeto(['GATA-3', is]), verbo([expressed]), complemento([at, a, high, level, in, 'naive,', freshly, activated, 'T', cells, and, 'Th2', lineage, 'cells,', but, subsides, to, a, minimal, level, in, 'Th1', lineage, cells, as, naive, cells, commit, to, their, 'Th', subset])]). relacion([sujeto(['Antisense', 'GATA-3']), verbo([inhibited]), complemento([the, expression, of, all, 'Th2', cytokine, genes, in, the, 'Th2', clone, 'D10'])]). relacion([sujeto(['GATA-3', directly]), verbo([activated]), complemento([an, 'IL-4', 'promoter-luciferase', reporter, gene, in, 'M12', cells])]). relacion([sujeto(['In', transgenic, 'mice,', elevated, 'GATA-3', in, 'CD4', 'T', cells]), verbo([caused]), complemento(['Th2', cytokine, gene, expression, in, developing, 'Th1', cells])]). relacion([sujeto(['The', 'GATA', family, of, vertebrate, 'DNA']), verbo([binding]), complemento([regulatory, proteins, are, expressed, in, diverse, tissues, and, at, different, times, of, development])]). relacion([sujeto(['However,', the, 'DNA']), verbo([binding]), complemento([regions, of, these, proteins, possess, considerable, homology, and, recognize, a, rather, similar, range, of, 'DNA', sequence, motifs])]). relacion([sujeto(['DNA']), verbo([binding]), complemento([is, mediated, through, two, 'domains,', each, containing, a, zinc, finger])]). relacion([sujeto(['Previous', results]), verbo([have]), complemento([led, to, the, conclusion, that, although, in, some, cases, the, 'N-terminal', finger, can, contribute, to, specificity, and, strength, of, 'binding,', it, does, not, bind, 'independently,', whereas, the, 'C-terminal', finger, is, both, necessary, and, sufficient, for, binding])]). relacion([sujeto(['Here', we, show, that, although, this, is, true, for, the, 'N-terminal', finger, of, 'GATA-1,', those, of, 'GATA-2', and, 'GATA-3', are, capable, of, strong, independent]), verbo([binding]), complemento([with, a, preference, for, the, motif, 'GATC'])]). relacion([sujeto(['Binding']), verbo([requires]), complemento([the, presence, of, two, basic, regions, located, on, either, side, of, the, 'N-terminal', finger])]). relacion([sujeto(['The', combination, of, a, single, finger, and, two, basic, regions, is, a, new, variant, of, a, motif, that]), verbo([has]), complemento([been, previously, found, in, the, binding, domains, of, other, finger, proteins])]). relacion([sujeto(['Our', results]), verbo([suggest]), complemento([that, the, 'DNA', binding, properties, of, the, 'N-terminal', finger, may, help, distinguish, 'GATA-2', and, 'GATA-3', from, 'GATA-1', and, the, other, 'GATA', family, members, in, their, selective, regulatory, roles, in, vivo])]). relacion([sujeto(['Using', 'ATL-16T', cells, which]), verbo([express]), complemento(['IL-5', 'mRNA,', we, have, identified, a, 'region,', within, the, human, 'IL-5', gene, 'promoter,', that, regulates, 'IL-5', gene, transcription])]). relacion([sujeto(['This', 'cis-acting', sequence, contains, the, core]), verbo([binding]), complemento(['motif,', '(', 'A/T)GATA(A/G),', for, 'GATA-binding', family, proteins, and, thus, suggests, the, involvement, of, these, family, members])]). relacion([sujeto(['In', this, 'report,', we, describe, the, cloning, of, human, 'GATA-4', '(', 'hGATA-4)', and, show, that, 'hGATA-4', selectively]), verbo([interacts]), complemento([with, the, -, 70, 'GATA', site, within, the, 'IL-5', proximal, promoter, region])]). relacion([sujeto(['ATL-16T', cells]), verbo([express]), complemento([mRNA, of, three, 'GATA-binding', 'proteins,', 'hGATA-2,', 'hGATA-3', and, 'hGATA-4,', and, each, of, them, has, a, potential, to, bind, to, the, consensus, '(', 'A/T)GATA(G/', 'A)', motif])]). relacion([sujeto(['However,', using, 'ATL-16T']), verbo([nuclear]), complemento(['extract,', we, demonstrated, that, 'GATA-4', is, the, only, 'GATA-binding', protein, that, forms, specific, 'DNA-protein', complex, with, the, -, 70, 'GATA', site])]). relacion([sujeto(['The', electrophoretic, mobility, shift, assay, with, extracts, of, 'COS', cells]), verbo([expressing]), complemento(['GATA-binding', proteins, showed, that, 'GATA-4', has, the, highest, binding, affinity, to, the, -, 70, 'GATA', site, among, the, three, 'GATA-binding', proteins])]). relacion([sujeto(['In', the, hematopoietic, 'lineage,', the, transcription, factors, 'GATA-1', and, 'GATA-2', show, restricted, and, largely, overlapping, expression, 'profiles,', but, 'GATA-2', is, uniquely]), verbo([expressed]), complemento([in, early, hematopoietic, progenitors])]). relacion([sujeto(['GATA-3', is]), verbo([found]), complemento([exclusively, in, 'T', cells, of, hematopoietic, lineage])]). relacion([sujeto(['GATA-3', mRNA, was]), verbo([expressed]), complemento([in, all, 'T-ALL', 'cases,', but, not, in, any, precursor, 'B-ALL'])]). relacion([sujeto(['These', findings]), verbo([suggest]), complemento([that, 'down-regulation', of, 'GATA-2', and, expression, of, 'GATA-3', are, important, events, for, the, commitment, of, cells, to, lymphoid, and, 'T', cell, 'lineage,', respectively])]). relacion([sujeto(['The', expression, profiles, of, 'GATA', factors, in, leukemic, cells, are, generally, consistent, with, those, in, their, normal, 'counterparts,', and, thus]), verbo([provide]), complemento([a, useful, tool, to, determine, the, lineage, commitment, of, unclassified, leukemia])]). relacion([sujeto(['To', evaluate, the, functional, role, of, 'GATA', motifs, in, the, 5, '\'', -, flanking, region, of, a, 'kidney-specific', 'AQP-2', water, channel, 'gene,', we, sought, to, isolate, a, 'GATA', 'factor(s)']), verbo([expressed]), complemento([in, collecting, ducts, and, determined, the, role, on, the, 'AQP-2', promoter])]). relacion([sujeto(['Reverse-transcription', 'PCR', using, dissected, nephron, segments, revealed, that, rat, 'GATA-3', but, not, 'GATA-2', was]), verbo([expressed]), complemento([in, collecting, 'ducts,', thus, indicating, that, 'GATA-3', could, interact, with, 'GATA', motifs, in, the, 'AQP-2', promoter])]). relacion([sujeto(['Transactivation', experiments, utilizing, the, rat, 'GATA-3', expression, vector, indicated, that, rat, 'GATA-3']), verbo([increased]), complemento([the, 'AQP-2', promoter, activity, about, fourfold])]). relacion([sujeto(['We', examined, regulation, of, the, human, erythropoietin, '(', 'Epo)', gene, through, the, 'GATA', sequence, in, the, 'Epo', promoter, and, showed, that, 'Hep3B', and, 'HepG2', cells]), verbo([express]), complemento([human, 'GATA-2', '(', 'hGATA-2)', mRNA, and, protein])]). relacion([sujeto(['Nuclear', extracts, of, 'QT6', cells, transfected, with, 'hGATA-1,', 2, ',', or, 3, transcription, factors, showed, specific]), verbo([binding]), complemento([to, the, 'GATA', element, in, the, human, 'Epo', gene, promoter, by, gel, mobility, shift, assay])]). relacion([sujeto(['Transient', transfection, of, 'Hep3B', cells, with, 'hGATA-1,', 2, ',', or, 3, showed, that, each, of, these, transcription, factors, significantly]), verbo([decreased]), complemento([the, level, of, expression, of, 'Epo', mRNA, as, assessed, by, a, competitive, polymerase, chain, reaction])]). relacion([sujeto(['Antisense', oligonucleotide, for, 'hGATA-2', transcription, factor, significantly]), verbo([increased]), complemento([the, 'Epo', protein, in, 'Hep3B', cells, under, 1, '%', 'O2', for, 24, hours, incubation])]). relacion([sujeto(['We', conclude, that, the, 'hGATA-1,', 2, ',', and, 3, transcription, factors, specifically]), verbo([bind]), complemento([to, the, 'GATA', element, in, the, human, 'Epo', gene, promoter, and, negatively, regulate, 'Epo', gene, expression])]). relacion([sujeto(['TAL1,', which, is, frequently]), verbo([activated]), complemento([in, 'T', cell, acute, lymphoblastic, leukemia, '(', 'T-ALL),', encodes, 'lineage-specific', basic, 'helix-loop-helix', '(', 'bHLH)', proteins, that, bind, specifically, to, 'E-box', 'DNA', motif, upon, dimerization, with, ubiquitous, basic, 'helix-loop-helix', proteins, 'E47', or, 'E12'])]). relacion([sujeto(['RBTN1', and, 'RBTN2,', also, frequently]), verbo([activated]), complemento([in, 'T-ALL,', encode, proteins, only, with, tandem, 'cysteine-rich', 'LIM', domains])]). relacion([sujeto(['We']), verbo([found]), complemento([that, aberrant, expression, of, 'TAL1', detected, in, 11, out, of, 14, 'T-ALL', cell, lines, was, invariably, accompanied, by, that, of, either, 'RBTN1', or, 'RBTN2'])]). relacion([sujeto(['Forced', expression, of, 'TAL1', together, with, 'RBTN1', or, 'RBTN2,', but, not, 'TAL1', 'alone,', strongly]), verbo([induced]), complemento([artificial, reporter, genes, in, a, 'TAL1/RBTN-negative', 'T-ALL', cell, 'line,', 'HPB-ALL'])]). relacion([sujeto(['Such', collaborative, transcriptional, activity, of, 'TAL1', and, 'RBTN', was, 'not,', 'however,', observed, in, 'non-T', cell, 'lines,']), verbo([suggesting]), complemento([further, involvement, of, some, 'T', 'cell-specific', cofactors])]). relacion([sujeto(['We', also, showed, that, coexpression, of, 'TAL1', and, 'RBTN1', in, 'HPB-ALL', strongly]), verbo([induced]), complemento(['TALLA1,', a, highly, specific, 'T-ALL', marker, whose, positivity, correlated, 100, '%', with, ectopic, expression, of, 'TAL1', among, various, 'T-ALL', cell, lines])]). relacion([sujeto(['Collectively,', ectopic, 'TAL1', and, 'RBTN1', or, -, 2, ',', together, with, some, endogenous, 'T', 'cell-specific', cofactors, like, 'GATA3,', constitute, a, highly, collaborative, set, of, transcription, factors, whose, aberrant, activity, in, 'T', cells, may]), verbo([lead]), complemento([to, leukemogenesis, by, modulating, expression, of, downstream, genes, such, as, 'TALLA1'])]). relacion([sujeto(['We', previously, demonstrated, that, the, zinc, finger, transcription, factors, 'GATA-2', and, 'GATA-3', are]), verbo([expressed]), complemento([in, trophoblast, giant, cells, and, that, they, regulate, transcription, from, the, mouse, placental, lactogen, 'I', gene, promoter, in, a, transfected, trophoblast, cell, line])]). relacion([sujeto(['We', present, evidence, here, that, both, of, these, factors]), verbo([regulate]), complemento([transcription, of, the, placental, lactogen, 'I', 'gene,', as, well, as, the, related, proliferin, 'gene,', in, trophoblast, giant, cells, in, vivo])]). relacion([sujeto(['Mutation', of, the, 'GATA-2', gene, had, a, similar, effect, on, placental, lactogen, 'I', 'expression,', but]), verbo([led]), complemento([to, a, markedly, greater, reduction, '(', 5, -, to, 6, -, 'fold)', in, proliferin, gene, expression])]). relacion([sujeto(['These', results, indicate, that, 'GATA-2', and, 'GATA-3', are, important, in, vivo, regulators, of, 'trophoblast-specific', gene, expression, and, placental, 'function,', and]), verbo([reveal]), complemento([a, difference, in, the, effect, of, these, two, factors, in, regulating, the, synthesis, of, related, placental, hormones])]). relacion([sujeto(['Commitment', and, differentiation, of, hematopoietic, stem, cells, are]), verbo([associated]), complemento([with, the, progressive, restriction, of, cellular, proliferation, and, the, progressive, expression, of, a, subset, of, genes, encoding, the, markers, of, mature, cells])]). relacion([sujeto(['These', two, processes, are, genetically]), verbo([regulated]), complemento(['and,', in, this, 'paper,', 'I', review, the, expression, and, function, of, the, 'GATA', family, of, transcription, factors, as, an, example, of, this, genetic, regulation])]). relacion([sujeto(['GATA', 'cis-acting', elements, are]), verbo([found]), complemento([in, most, of, the, regulatory, regions, of, 'T-lymphoid,', erythrocytic, and, megakaryocytic, restricted, genes])]). relacion([sujeto(['These', 'GATA', motifs, are]), verbo([recognized]), complemento([by, the, members, of, a, family, of, transcriptional, 'regulators:', the, 'GATA', family])]). relacion([sujeto(['Three', members, of, this, 'family,', 'GATA-1,', 2, and, 3, are]), verbo([expressed]), complemento([in, hematopoietic, cells])]). relacion([sujeto(['THE', 'zinc-finger', transcription, factor, 'GATA-3', is]), verbo([expressed]), complemento([in, haematopoietic, cells, and, in, the, developing, kidney, and, nervous, system])]). relacion([sujeto(['Functionally', important, 'GATA-3']), verbo([binding]), complemento([sites, have, been, identified, in, multiple, 'T-cell-specific', genes])]). relacion([sujeto(['Here', we]), verbo([have]), complemento([used, murine, embryonic, stem, '(', 'ES)', cells, containing, homozygous, mutations, in, the, 'GATA-3', gene, '(', 'GATA-3(-/-))', in, conjunction, with, the, 'RAG-2(-/-)', '(', ref])]). relacion([sujeto(['These', findings]), verbo([suggest]), complemento([that, 'GATA-3', is, an, essential, and, specific, regulator, of, early, thymocyte, development])]). relacion([sujeto(['Flow', cytometric, and, immunocytochemical, analyses, of, murine, fetal, thymus, '(', 'FT)', cells, with, antibodies, to, various, surface, markers, and, transcription, factors]), verbo([reveal]), complemento([that, the, synthesis, of, 'TCF-1', and, 'GATA-3', protein, begins, simultaneously, in, a, fraction, of, the, most, immature, population, of, 'FT', 'cells,', which, have, the, phenotype, of, 'CD4-CD8-CD44+CD25-'])]). relacion([sujeto(['No', 'TCF-1-producing', cells, is]), verbo([found]), complemento([in, the, fetal, liver, '(', 'FL)'])]). relacion([sujeto(['It', is, also]), verbo([found]), complemento([that, the, 'T', cell, development, from, 'FL,', but, not, 'FT,', progenitors, in, the, 'FT', organ, culture, system, is, severely, inhibited, by, the, addition, of, antisense, oligonucleotides, for, either, 'TCF-1', or, 'GATA-3'])]). relacion([sujeto(['These', results, strongly]), verbo([suggest]), complemento([that, 'TCF-1', and, 'GATA-3', play, essential, roles, in, the, initiation, of, the, earliest, steps, of, 'T', cell, development, in, the, thymus])]). relacion([sujeto(['Based', on, the, presence, of, 'T', cell, 'receptor-beta', '(', 'TcR-beta)', gene, rearrangements, in, 'L428', and, 'HDLM-1', 'cells,', the, expression, of, 'CD2', in, 'HDLM-1', 'cells,', and, the, presence, of, immunoglobulin, 'heavy-chain', '(', 'IgH)', gene, rearrangement, in, 'KM-H2', 'cells,', some, researchers]), verbo([have]), complemento([concluded, that, these, 'long-term', cell, lines, derived, from, patients, with, 'Hodgkin\'s', disease, are, lymphoid, in, nature])]). relacion([sujeto(['The', information, obtained, from, these, cell, lines]), verbo([has]), complemento([also, been, used, in, arguments, for, a, lymphoid, origin, of, 'H-RS', cells, in, tissue, despite, the, frequent, absence, of, lymphoid, markers, and, 'Ig/TcR', gene, rearrangements, in, these, cells])]). relacion([sujeto(['We', questioned, whether, one, can, use, the, limited, expression, of, lymphoid, markers, or, the, limited, gene, rearrangement, to, conclude, that, 'H-RS', cells]), verbo([have]), complemento([a, lymphoid, 'origin,', because, these, markers, may, be, aberrant, in, tumor, cells])]). relacion([sujeto(['The', sensitivity, and, specificity, of, this, assay, for, determination, of, cell, lineage]), verbo([have]), complemento([been, established, in, a, large, number, of, cultured, human, and, murine, cell, lines])]). relacion([sujeto(['The']), verbo([nuclear]), complemento([distribution, of, 'GATA', transcription, factors, in, murine, haemopoietic, cells, was, examined, by, indirect, immunofluorescence])]). relacion([sujeto(['These', 'foci,', which, were, preferentially]), verbo([found]), complemento([adjacent, to, nucleoli, or, at, the, nuclear, 'periphery,', did, not, represent, sites, of, active, transcription, or, binding, of, 'GATA-1', to, consensus, sites, in, the, 'beta-globin', loci])]). relacion([sujeto(['The', 'GATA-1']), verbo([nuclear]), complemento([bodies, differed, from, previously, described, nuclear, structures, and, there, was, no, 'co-localization', with, nuclear, antigens, involved, in, 'RNA', processing, or, other, ubiquitous, '(', 'Spl,', 'c-Jun', and, 'TBP)', or, haemopoietic, '(', 'NF-E2)', transcription, factors])]). relacion([sujeto(['Interestingly,', 'GATA-2', and, 'GATA-3', proteins, also, localized, to, the, same]), verbo([nuclear]), complemento([bodies, in, cell, lines, 'co-expressing', 'GATA-1', and, -, 2, or, 'GATA-1', and, -, 3, gene, products])]). relacion([sujeto(['This', pattern, of, distribution, 'is,', thus, 'far,', unique, to, the, 'GATA', transcription, factors, and]), verbo([suggests]), complemento([a, 'protein-protein', interaction, with, other, components, of, the, nuclear, bodies, via, the, 'GATA', zinc, finger, domain])]). relacion([sujeto(['Using', a, 'cell-free', degradation, assay, and, 'site-directed', 'mutagenesis,', we]), verbo([report]), complemento([here, that, the, three, 'PEST', motifs, of, 'c-fos', are, not, required, for, rapid, cleavage, by, calpains])]). relacion([sujeto(['Accumulating', evidence]), verbo([suggests]), complemento([a, role, for, cAMP, as, an, 'immunomodulator;', agents, that, increase, intracellular, cAMP, levels, have, been, shown, to, inhibit, production, of, cytokines, predominantly, produced, by, 'T', helper, '(', 'Th)', 1, cells, such, as, 'IL-2', and, interferon, gamma, '(', 'IFN-gamma)'])]). relacion([sujeto(['In', 'contrast,', the, production, of, 'IL-5,', predominantly, produced, by, 'Th2', 'cells,', is, actually]), verbo([enhanced]), complemento([by, these, agents])]). relacion([sujeto(['In', this, 'report,', we]), verbo([have]), complemento([performed, transient, transfection, experiments, with, 'IL-5', 'promoter-reporter', gene, 'constructs,', 'DNase', 'I', footprinting, 'assays,', and, electrophoretic, mobility, shift, assays, to, investigate, the, key, regulatory, regions, necessary, for, activation, of, the, 'IL-5', promoter, by, dibutyryl, cAMP, and, phorbol, esters, in, the, mouse, thymoma, line, 'EL-4'])]). relacion([sujeto(['Taken', 'together,', our, data, demonstrate, the, critical, importance, of, two, sequences, within, the, 'IL-5', 5, '\'', -, flanking, region, for, activation, by, these, agents, in, 'EL-4', 'cells:', 'one,', a, highly]), verbo([conserved]), complemento([15, -, base, pair, element, present, in, genes, expressed, by, 'Th2', 'cells,', called, the, conserved, lymphokine, element, 0, '(', 'CLE0;', located, between, -, 53, and, -, 39, in, the, 'IL-5', 'promoter),', and, the, 'other,', two, overlapping, binding, sites, for, the, transcription, factor, 'GATA-3', '(', but, not, 'GATA-4)', between, -, 70, and, -, 59])]). relacion([sujeto(['Taken', 'together,', our, data]), verbo([suggest]), complemento([that, activation, via, the, unique, sequence, combination, 'GATA/CLE0', results, in, selective, expression, of, the, 'IL-5', gene, in, response, to, elevated, levels, of, intracellular, cAMP])]). relacion([sujeto(['We']), verbo([report]), complemento([here, the, isolation, of, a, human, cDNA, clone, which, encodes, a, 3, '\'', segment, of, a, novel, protein, with, three, zinc, fingers])]). relacion([sujeto(['This', 'protein,', which, we, termed, 'G3B,', can]), verbo([interact]), complemento([with, 'GATA-3', in, vitro])]). relacion([sujeto(['Its', mRNA, is]), verbo([expressed]), complemento([in, 'T', and, 'B', cells])]). relacion([sujeto(['We']), verbo([have]), complemento([designed, a, new, strategy, to, isolate, unknown, 'DNA', regions, interacting, with, one, or, several, related, regulatory, proteins])]). relacion([sujeto(['It']), verbo([involves]), complemento([trapping, such, 'DNAs', by, their, cognate, binding, proteins, followed, by, 'PCR', 'amplification,', as, described, previously, '[', 'Kinzler,', 'K'])]). relacion([sujeto(['To', overcome, the, inability, of, such, a, procedure, to, discriminate, between, functional, and, 'non-functional']), verbo([binding]), complemento([sites, as, well, as, to, specifically, trap, short, 'DNA', motifs, from, the, whole, higher, eukaryotic, 'genome,', we, have, used, as, starting, material, 'DNA', isolated, from, transcriptionally, competent, chromatin, 'fractions,', instead, of, total, genomic, 'DNA'])]). relacion([sujeto(['To', test, our, 'strategy,', we, selected, human, 'DNA', sequences, that]), verbo([bind]), complemento([members, of, the, 'GATA', 'family,', known, to, recognize, similar, 'WGATAR', motifs])]). relacion([sujeto(['These', proteins, are]), verbo([expressed]), complemento([in, different, cell, types, in, which, they, regulate, the, transcription, of, different, sets, of, 'genes;', 'thus,', transcriptionally, active, chromatin, containing, 'GATA', motifs, should, differ, according, to, the, cell, type])]). relacion([sujeto(['We']), verbo([have]), complemento([trapped, and, analyzed, 'DNA', fragments, isolated, from, an, active, chromatin, 'fraction,', from, erythroid, cells, and, lymphoid, 'cells,', using, 'GATA-1', and, 'GATA-3', 'proteins,', respectively])]). relacion([sujeto(['GATA-3', is, one, member, of, a, growing, family, of, related, transcription, factors, which, share, a, strongly]), verbo([conserved]), complemento([expression, pattern, in, all, vertebrate, organisms])]). relacion([sujeto(['In', order, to, elucidate, 'GATA-3', function, using, a, direct, genetic, 'approach,', we]), verbo([have]), complemento([disrupted, the, murine, gene, by, homologous, recombination, in, embryonic, stem, cells])]). relacion([sujeto(['Reporter', gene, transfection, experiments]), verbo([have]), complemento([indicated, that, a, 'GATA', site, and, an, 'AP1', site, are, essential, for, 'ET-1', promoter, function, in, endothelial, 'cells,', and, 'GATA-2', appears, to, be, the, active, 'GATA', factor, which, regulates, 'ET-1', expression])]). relacion([sujeto(['Cooperativity', between, the, 'AP1', complex, and, 'GATA-2', was, observed, as, a, synergistic]), verbo([increase]), complemento([in, transcriptional, activity, of, the, 'ET-1', reporter, plasmid])]). relacion([sujeto(['Experiments', with, 'GATA-1', and, 'GATA-3', expression, vectors]), verbo([provided]), complemento([evidence, that, this, capacity, to, interact, with, 'AP1', may, be, a, characteristic, of, all, 'GATA', family, members])]). relacion([sujeto(['Biochemical', evidence, for, 'AP1-GATA', interaction, was]), verbo([provided]), complemento([by, immunoprecipitation, experiments])]). relacion([sujeto(['Also,', antisera, directed, against, 'Jun', and, 'Fos', were, able, to, immunoprecipitate, from]), verbo([nuclear]), complemento([extracts, a, 'GATA-binding', 'protein,', indicating, the, association, of, 'AP1', and, 'GATA', proteins, in, vivo])]). relacion([sujeto(['Using', 'ATL-16T', cells, which]), verbo([express]), complemento(['IL-5', 'mRNA,', we, have, identified, a, region, within, the, human, 'IL-5', gene, promoter, that, regulates, 'IL-5', gene, transcription])]). relacion([sujeto(['This', 'cis-acting', sequence, contains, the, core]), verbo([binding]), complemento(['motif,', '(', 'A/T)GATA(A/G),', for, 'GATA-binding', family, proteins, and, thus, suggests, the, involvement, of, this, family, members])]). relacion([sujeto(['In', this, 'report,', we, describe, the, cloning, of, human, 'GATA-4', '(', 'hGATA-4)', and, show, that, 'hGATA-4', selectively]), verbo([interacts]), complemento([with, the, -, 70, 'GATA', site, within, the, 'IL-5', proximal, promoter, region])]). relacion([sujeto(['ATL-16T', cells]), verbo([express]), complemento([mRNAs, of, three, 'GATA-binding', 'proteins,', 'hGATA-2,', 'hGATA-3,', and, 'hGATA-4,', and, each, of, them, has, a, potential, to, bind, to, the, consensus, '(', 'A/T)GATA(G/A)', motif])]). relacion([sujeto(['However,', using, 'ATL-16T']), verbo([nuclear]), complemento(['extract,', we, demonstrated, that, 'GATA-4', is, the, only, 'GATA-binding', protein, that, forms, a, specific, 'DNA-protein', complex, with, the, -, 70, 'GATA', site])]). relacion([sujeto(['An', electrophoretic, mobility, shift, assay, with, extracts, of, 'COS', cells]), verbo([expressing]), complemento(['GATA-binding', proteins, showed, that, 'GATA-4', has, the, highest, binding, affinity, for, the, -, 70, 'GATA', site, among, the, three, 'GATA-binding', proteins])]). relacion([sujeto(['GATA-3', is, a, transcription, factor]), verbo([involved]), complemento([in, the, differentiation, of, 'T', lymphocytes, and, additionally, expressed, in, several, chicken, and, mouse, embryonic, tissues])]). relacion([sujeto(['Using', in, situ, 'hybridization,', we]), verbo([found]), complemento([that, the, human, 'GATA-3', gene, is, selectively, expressed, in, the, developing, kidney])]). relacion([sujeto(['GATA-3', mRNA, is, first, detected, in, the, 'Wolffian', duct, from, the, time, of, its, emergence, in, the, embryonic, intermediate, mesoderm, and, further]), verbo([expressed]), complemento([in, the, collecting, ducts, of, the, mesonephros, until, its, involution])]). relacion([sujeto(['In', the, 'metanephros,', 'GATA-3', is]), verbo([expressed]), complemento([in, the, ureteric, bud, where, it, is, constitutively, 'transcribed,', throughout, 'development,', along, the, branching, process, that, gives, rise, to, the, whole, collecting, system, of, the, definitive, kidney])]). relacion([sujeto(['Besides', the, 'Wolffian', duct, and, 'derivatives,', we, also]), verbo([report]), complemento([the, expression, of, 'GATA-3', gene, in, the, glomerular, mesangium, and, adjacent, endocapillary, 'cells,', in, both, 'meso-', and, metanephros])]). relacion([sujeto(['This', early, and, specific, expression, of, the, 'GATA-3', gene]), verbo([suggests]), complemento([a, role, for, this, transcription, factor, in, the, differentiation, of, the, human, kidney])]). relacion([sujeto(['Although', it]), verbo([has]), complemento([rearranged, 'in-frame', the, two, alleles, of, the, heavy, 'chain,', deleted, one, light, chain, 'locus,', and, rearranged, abortively, the, two, alleles, of, the, second, light, chain, 'locus,', the, cell, line, does, not, produce, immunoglobulin, molecules, or, message])]). relacion([sujeto(['It']), verbo([expresses]), complemento([a, variety, of, 'T-cell', characteristic, markers, such, as, 'Xenopus', pan, 'T-cell', 'markers,', 'CD8', equivalent, and, 'GATA3', transcription, factor])]). relacion([sujeto(['It', does, not]), verbo([express]), complemento([any, major, histocompatibility, complex, class, 'I', or, class, 'II', molecules])]). relacion([sujeto(['In', order, to, understand, the, role, of, the, transcription, factor, 'GATA', 3, in, vertebrate, 'development,', we]), verbo([have]), complemento([examined, its, expression, and, some, aspects, of, its, regulation, during, gastrulation, and, neurulation, in, the, zebrafish])]). relacion([sujeto(['Analysis', of, expression, patterns, by, in, situ, hybridisation, shows, the, gene, to, be]), verbo([expressed]), complemento([during, gastrulation, in, the, ventral, region, of, the, embryo, which, includes, tissue, fated, to, form, the, 'non-neural', ectoderm])]). relacion([sujeto(['Subsequently,', gta3]), verbo([expresses]), complemento([in, the, pronephric, duct, and, in, defined, regions, of, the, central, nervous, system, which, include, specific, cells, in, each, segment, of, the, spinal, cord, and, nuclei, in, the, brain])]). relacion([sujeto(['Double', labelling, embryos, with, a, probe, for, gta3, and, antibodies, which, identify, differentiated, neurons]), verbo([suggest]), complemento([that, gta3, is, dynamically, expressed, during, the, early, differentiation, phase, of, a, subset, of, neurons, but, not, in, the, terminal, phase])]). relacion([sujeto(['We']), verbo([have]), complemento([previously, shown, that, 'SCL,', 'GATA-1', and, 'GATA-2', are, expressed, in, multipotent, progenitors, prior, to, lineage, 'commitment,', but, are, 'down-regulated', during, 'granulocyte/monocyte', differentiation])]). relacion([sujeto(['The', phenomenon, of, gene, extinction, in, cell, hybrids, may]), verbo([reveal]), complemento([negative, regulatory, mechanisms, operating, during, normal, differentiation])]). relacion([sujeto(['We']), verbo([have]), complemento([therefore, analysed, the, regulation, of, 'SCL,', 'GATA-1,', 'GATA-2', and, 'GATA-3', in, cell, hybrids, formed, by, the, fusion, of, cell, lines, representing, different, haemopoietic, lineages])]). relacion([sujeto(['Expression', of, 'GATA-3', was, extinguished, in, both, human, and, murine, erythroid, x, 'T', cell, 'hybrids,', an, observation, which]), verbo([suggests]), complemento([that, erythroid, cells, contain, factors, capable, of, repressing, 'GATA-3', expression])]). relacion([sujeto(['These', data]), verbo([suggest]), complemento([that, 'T', cells, and, 'B', cells, do, not, contain, 'trans-acting', factors, capable, of, 'down-regulating', expression, of, 'SCL,', 'GATA-1', or, 'GATA-2,', and, therefore, raise, the, possibility, that, a, '\'', hit, and, 'run\'', mechanism, may, repress, these, genes, during, normal, haemopoiesis])]). relacion([sujeto(['These', results]), verbo([provide]), complemento([the, first, analysis, of, 'SCL', and, 'GATA', gene, regulation, in, stable, cell, hybrids])]). relacion([sujeto(['ES', cells, in, which, the, gene, for, the, erythroid, transcription, factor, 'GATA-1']), verbo([has]), complemento([been, disrupted, fail, to, produce, mature, erythroid, cells, either, in, vivo, or, in, vitro])]). relacion([sujeto(['With', the, 'EB', in, vitro, differentiation, 'assay,', constructs]), verbo([expressing]), complemento([heterologous, 'GATA-binding', proteins, were, tested, for, their, abilities, to, correct, the, developmental, defect, of, 'GATA-1-deficient', 'ES', cells])]). relacion([sujeto(['Furthermore,', 'GATA-3', and, 'GATA-4,', which, are, normally]), verbo([expressed]), complemento([in, different, 'tissues,', and, a, protein, consisting, of, the, zinc, fingers, of, 'GATA-1', fused, to, the, herpes, simplex, virus, 'VP16', transcription, activation, domain, were, able, to, compensate, for, the, 'GATA-1', defect])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, neither, the, transcription, activation, domains, of, 'mGATA-1', nor, its, zinc, fingers, impart, erythroid, cell, specificity, for, its, action, in, vivo])]). relacion([sujeto(['Rather,', it, appears, that, specificity, is]), verbo([mediated]), complemento([through, the, 'cis-acting', control, regions, which, determine, spatial, and, temporal, expression, of, the, 'GATA-1', gene])]). relacion([sujeto(['Furthermore,', our, results, demonstrate, that, the, zinc, finger, region, may]), verbo([have]), complemento([a, biological, function, in, addition, to, mediating, 'DNA', binding])]). relacion([sujeto(['The', 'GATA', family, of, transcription, factors]), verbo([regulates]), complemento([a, wide, variety, of, 'genes,', including, those, involved, in, differentiation, of, erythrocytes, and, 'T', lymphocytes])]). relacion([sujeto(['We']), verbo([report]), complemento([here, the, creation, of, a, dominant, negative, mutant, of, 'GATA-3,', 'KRR,', which, effectively, blocks, 'wild-type', 'GATA-1,', 'GATA-2,', and, 'GATA-3', transactivation, when, 'co-expressed', in, transient, assays])]). relacion([sujeto(['The', 'GATA-3', 'KRR', mutation, does, not, affect, 'expression,']), verbo([nuclear]), complemento(['translocation,', or, the, ability, to, bind, to, a, consensus, 'GATA', sequence])]). relacion([sujeto(['KRR', can]), verbo([suppress]), complemento([the, activity, of, the, minimal, 'T', cell, receptor, '(', 'TCR)', alpha, and, beta, enhancers, by, 12, -, and, 3.4, -, 'fold,', respectively])]). relacion([sujeto(['However,', 'KRR', did, not]), verbo([have]), complemento([a, significant, effect, on, the, activity, of, larger, 'TCR-alpha', and, -, beta, enhancer, fragments])]). relacion([sujeto(['Thus,', functional, redundancy, in, the, 'TCR-alpha', and, -, beta, enhancers, can, compensate, for, the]), verbo([loss]), complemento([of, 'GATA-3', activity])]). relacion([sujeto(['In', continuing, our, analysis, of, the, 'trophoblast-specific', expression, of, the, mouse, placental, lactogen, 'I', 'gene,', we, now, demonstrate, that, the, transcription, factors, 'GATA-2', and, 'GATA-3']), verbo([regulate]), complemento([the, activity, of, this, gene, promoter])]). relacion([sujeto(['These', factors, are]), verbo([expressed]), complemento([in, placental, trophoblast, 'cells,', with, peak, levels, of, the, 'GATA-2,', 'GATA-3', and, placental, lactogen, 'I', mRNAs, each, accumulating, at, midgestation])]). relacion([sujeto(['Analysis', of, a, region, of, the, placental, lactogen, 'I', gene, 'promoter,', previously, shown, to, be, sufficient, for, directing, 'trophoblast-specific', 'transcription,', revealed, the, presence, of, three, consensus]), verbo([binding]), complemento([sites, for, 'GATA-2', or, 'GATA-3'])]). relacion([sujeto(['Both', 'GATA-2', and, 'GATA-3']), verbo([bind]), complemento([to, these, sites, in, vitro, and, mutation, of, these, sites, results, in, a, significant, decrease, in, promoter, activity, as, assayed, by, transient, transfection, into, the, 'choriocarcinoma-derived', cell, line, 'Rcho-1,', which, expresses, endogenous, 'GATA-2', and, 'GATA-3'])]). relacion([sujeto(['Furthermore,', overexpression, of, 'GATA', factors, in, 'Rcho-1', cells]), verbo([stimulates]), complemento([transcription, from, a, 'co-transfected', placental, lactogen, 'I', gene, promoter])]). relacion([sujeto(['Most', 'significantly,', expression, of, 'GATA-2', or, 'GATA-3', was]), verbo([found]), complemento([to, induce, transcription, from, this, promoter, in, transfected, 'non-trophoblast', '(', 'fibroblast)', cells])]). relacion([sujeto(['These', data, indicate, that, 'GATA', factors, are, both, limiting, and]), verbo([required]), complemento([transcriptional, regulatory, molecules, in, placental, 'trophoblasts,', and, that, the, tissue, specificity, of, the, placental, lactogen, 'I', gene, is, 'determined,', at, least, in, 'part,', by, 'GATA-2', 'and/or', 'GATA-3'])]). relacion([sujeto(['In', situ, hybridization, shows, that, 'mGATA-3', mRNA, accumulation, is, temporally, and, spatially]), verbo([regulated]), complemento([during, early, 'development:', although, found, most, abundantly, in, the, placenta, prior, to, 10, days, of, 'embryogenesis,', 'mGATA-3', expression, becomes, restricted, to, specific, cells, within, the, embryonic, central, nervous, system, '(', in, the, 'mesencephalon,', 'diencephalon,', pons, and, inner, 'ear)', later, in, gestation])]). relacion([sujeto(['In', addition, to, this, distinct, pattern, in, the, nervous, 'system,', 'mGATA-3', is, also]), verbo([expressed]), complemento([in, the, embryonic, kidney, and, the, thymic, 'rudiment,', and, further, analysis, showed, that, it, is, expressed, throughout, 'T', lymphocyte, differentiation])]). relacion([sujeto(['At', least, two, regulatory, elements, '(', one, positive, and, one, 'negative)', appear, to, be]), verbo([required]), complemento([for, appropriate, 'tissue-restricted', regulation, after, transfection, of, 'mGATA-3-directed', reporter, genes, into, cells, that, naturally, express, 'GATA-3', '(', 'T', lymphocytes, and, neuroblastoma, 'cells)'])]). relacion([sujeto(['Furthermore,', this, same, region, of, the, locus]), verbo([confers]), complemento([developmentally, appropriate, expression, in, transgenic, 'mice,', but, only, in, a, subset, of, the, tissues, that, naturally, express, the, gene])]). relacion([sujeto(['The', human, glycoprotein, hormone, 'alpha-subunit', gene, is]), verbo([expressed]), complemento([in, two, quite, dissimilar, 'tissues,', the, placenta, and, anterior, pituitary])]). relacion([sujeto(['In', the, 'placenta,', a, composite, enhancer]), verbo([confers]), complemento([specific, expression])]). relacion([sujeto(['It', contains, four, 'protein-binding', 'sites:', two, cyclic, 'AMP', '(', 'cAMP)', response, elements, that]), verbo([bind]), complemento(['CREB,', a, 'trophoblast-specific', element, that, binds, 'TSEB,', and, a, sequence, 'motif,', 'AGATAA,', that, matches, the, consensus, binding, site, for, a, family, of, transcription, factors, termed, the, 'GATA-binding', proteins])]). relacion([sujeto(['In', pituitary, 'gonadotropes,', the, cAMP, response, elements, remain, important, for, 'expression,', 'TSEB', is, 'absent,', and, elements, further, upstream]), verbo([participate]), complemento([in, 'tissue-specific', expression])]). relacion([sujeto(['Here', we, establish, a, regulatory, role, for, the, 'GATA', element, in, both, the, placenta, and, pituitary, by, demonstrating, that, a, mutation, of, this, element]), verbo([decreases]), complemento(['alpha-subunit', gene, expression, 15, -, fold, in, 'JEG-3', human, placental, cells, and, 2.5, -, fold, in, alpha, 'T3-1', mouse, pituitary, gonadotropes])]). relacion([sujeto(['In', 'JEG-3', 'cells,', human, 'GATA-2', '(', 'hGATA-2)', and, 'hGATA-3', are, highly]), verbo([expressed]), complemento([and, both, proteins, bind, to, the, 'alpha-subunit', gene, 'GATA', element])]). relacion([sujeto(['In', alpha, 'T3-1', 'cells,', the, 'GATA', motif, is]), verbo([bound]), complemento([by, mouse, 'GATA-2', '(', 'mGATA-2)', and, an, 'mGATA-4-related', protein])]). relacion([sujeto(['Cotransfection', of, 'hGATA-2', or, 'hGATA-3', into, alpha, 'T3-1', cells]), verbo([activates]), complemento([the, 'alpha-subunit', gene, threefold])]). relacion([sujeto(['These', studies, establish, a, role, for, the, 'GATA-binding', proteins, in, placental, and, pituitary, 'alpha-subunit', gene, 'expression,', significantly, expanding, the, known]), verbo([target]), complemento([genes, of, 'GATA-2,', 'GATA-3,', and, perhaps, 'GATA-4'])]). relacion([sujeto(['Three', 'high-affinity']), verbo([binding]), complemento([sites, for, the, 'GATA', family, of, transcriptional, regulators, have, been, identified, within, the, 'T-cell', receptor, 'beta-chain', '(', 'TCR', 'beta)', transcriptional, 'enhancer,', and, their, functional, significance, has, been, determined, in, an, effort, to, understand, the, 'T-cell', specificity, of, the, enhancer, more, fully])]). relacion([sujeto(['Neither', site, 'TE1', nor, site, 'TE2', can, functionally, replace, a, mutated, 'TE4', site, in, 'T', 'cells;', 'however,', the, same, 'protein,', probably, 'GATA-3,']), verbo([binds]), complemento([all, three, 'sites,', as, judged, by, electrophoretic, mobility, 'shift,', oligonucleotide, 'competition,', and, proteolytic, clipping, assays])]). relacion([sujeto(['These', data]), verbo([suggest]), complemento([that, additional, proteins, are, critical, for, the, ability, of, 'GATA-3', to, activate, the, 'TCR', beta, enhancer])]). relacion([sujeto(['In', 'fibroblasts,', the, 'GATA', sequence, at, site, 'TE1', appears, to]), verbo([bind]), complemento([a, negative, regulator])]). relacion([sujeto(['Since', this, is, not, true, in, 'B', 'cells,', 'B', cells, and, fibroblasts, appear, to]), verbo([have]), complemento([different, mechanisms, for, negative, regulation, of, the, 'TCR', beta, enhancer])]). relacion([sujeto(['To', define, the, consequences, of, 'GATA-1']), verbo([loss]), complemento([more, 'precisely,', we, used, an, in, vitro, 'ES', cell, differentiation, assay, that, permits, enumeration, of, primitive, '(', 'EryP)', and, definitive, '(', 'EryD)', erythroid, precursors, and, recovery, of, pure, erythroid, colonies])]). relacion([sujeto(['EryD', 'precursors,', 'however,', are, normal, in, number, but, undergo, developmental]), verbo([arrest]), complemento([and, death, at, the, proerythroblast, stage])]). relacion([sujeto(['Contrary', to, initial, 'expectations,']), verbo([arrested]), complemento(['GATA-1(-)-definitive', proerythroblasts, express, 'GATA', target, genes, at, normal, levels])]). relacion([sujeto(['These', findings, imply, substantial, interchangeability, of, 'GATA', factors, in, vivo, and]), verbo([suggest]), complemento([that, 'GATA-1', normally, serves, to, repress, 'GATA-2', during, erythropoiesis])]). relacion([sujeto(['The', approach, used, here, is, a, paradigm, for, the, phenotypic, analysis, of]), verbo([targeted]), complemento([mutations, affecting, hematopoietic, development])]). relacion([sujeto(['GATA3,', a, member, of, the, 'GATA', family, that, is, abundantly]), verbo([expressed]), complemento([in, the, 'T-lymphocyte', 'lineage,', is, thought, to, participate, in, 'T-cell', receptor, gene, activation, through, binding, to, enhancers])]). relacion([sujeto(['The', two, human, 'GATA3', zinc, fingers, are, encoded, by, two, separate, exons, highly]), verbo([conserved]), complemento([with, those, of, 'GATA1,', but, no, other, structural, homologies, between, these, two, genes, can, be, found])]). relacion([sujeto(['The', promoter, sequence, analysis, of, these, two, genes, revealed, that, they, are, embedded, within, a, 'CpG', island, and, share, structural, features, often]), verbo([found]), complemento([in, the, promoters, of, housekeeping, genes])]). relacion([sujeto(['Individual', members, of, a, recently, identified, family, of, transcriptional, regulatory, 'proteins,', the, 'GATA', 'factors,', are]), verbo([required]), complemento([for, the, differentiation, of, certain, hematopoietic, cell, lineages])]). relacion([sujeto(['We', show, here, that, two, of, the, members, of, this, gene, 'family,', 'GATA-2', and, 'GATA-3,', are]), verbo([expressed]), complemento([within, discrete, cell, populations, of, the, chicken, optic, tectum, during, 'embryogenesis,', and, that, they, have, highly, restricted, patterns, of, expression, in, the, developing, chicken, brain])]). relacion([sujeto(['The', observation, that, both, the, timing, of, appearance, and, the, localization, of, expression, of, 'GATA-2', and, 'GATA-3', are, correlated, with, optic, tectum, development]), verbo([suggest]), complemento([that, these, transcription, factors, may, be, associated, with, the, initiation, of, gene, transcription, required, for, the, determination, of, specific, neuronal, fates, within, visual, areas, of, the, vertebrate, brain])]). relacion([sujeto(['GATA-3', is, a, zinc, finger, transcription, factor, which, is]), verbo([expressed]), complemento([in, a, highly, restricted, and, strongly, conserved, tissue, distribution, pattern, in, vertebrate, 'organisms,', 'specifically,', in, a, subset, of, hematopoietic, 'cells,', in, cells, within, the, central, and, peripheral, nervous, 'systems,', in, the, 'kidney,', and, in, placental, trophoblasts])]). relacion([sujeto(['Tissue-specific', cellular, genes]), verbo([regulated]), complemento([by, 'GATA-3', have, been, identified, in, 'T', lymphocytes, and, the, 'placenta,', while, 'GATA-3-regulated', genes, in, the, nervous, system, and, kidney, have, not, yet, been, defined])]). relacion([sujeto(['The', results, of, these, experiments, show, some, anticipated, 'phenotypes,', for, 'example,', the, definition, of, discrete, domains]), verbo([required]), complemento([for, specific, 'DNA-binding', site, recognition, '(', amino, acids, 303, to, 348, ')', and, trans, activation, '(', amino, acids, 30, to, 74, ')'])]). relacion([sujeto(['The', signaling, sequence, for]), verbo([nuclear]), complemento([localization, of, human, 'GATA-3', is, a, property, conferred, by, sequences, within, and, surrounding, the, amino, finger, '(', amino, acids, 249, to, 311, ')', of, the, 'protein,', thereby, assigning, a, function, to, this, domain, and, thus, explaining, the, curious, observation, that, this, zinc, finger, is, dispensable, for, 'DNA', binding, by, the, 'GATA', family, of, transcription, factors])]). relacion([sujeto(['The', 'DNA', motif, 'WGATAR']), verbo([has]), complemento([been, identified, within, transcriptional, regulatory, domains, of, globin, and, other, 'erythroid-specific', genes, and, the, activator, proteins, that, bind, to, this, regulatory, 'element,', the, 'GATA', 'factors,', belong, to, a, 'multi-gene', family, that, is, expressed, in, chicken, erythroid, cells])]). relacion([sujeto(['Here', we, show, 'that,', as, in, 'chickens,', multiple, members, of, the, 'GATA', factor, family, are]), verbo([expressed]), complemento([in, human, and, murine, erythroid, cells])]). relacion([sujeto(['During', the, early, stages, of, chicken, embryogenesis, '(', well, before, blood, island, 'formation),', each, of, the, 'GATA', family, members, is]), verbo([transcribed]), complemento([with, a, unique, temporal, and, spatial, pattern])]). relacion([sujeto(['In', the, primitive, erythroid, 'lineage,', transcription, of, the, embryonic, 'epsilon-globin', gene, parallels, 'GATA-1', expression, while, the, switch, to, 'beta-globin', transcription, in, definitive, erythroid, cells, is, directly, preceded, by, a, pronounced]), verbo([increase]), complemento([in, 'GATA-3', accumulation])]). relacion([sujeto(['The', timing, and, pattern, of, expression, of, these, different, mRNAs, during, avian, erythroid, development, and, differentiation]), verbo([suggests]), complemento([that, temporally, regulated, changes, in, 'GATA', factor, expression, are, required, for, vertebrate, hematopoiesis])]). relacion([sujeto(['Genes', encoding, the, accessory, molecules, 'CD8', and, 'CD4', are]), verbo([activated]), complemento([early, in, thymocyte, 'development,', generating, 'CD4+8+', double, positive, 'intermediates,', which, give, rise, to, two, functionally, distinct, mature, 'T', cell, subsets, that, express, either, 'CD4', or, 'CD8'])]). relacion([sujeto(['To', identify, the, key, regulatory, 'factors,', we]), verbo([have]), complemento([initiated, an, analysis, of, the, transcriptional, regulation, of, the, murine, 'CD8', alpha, gene])]). relacion([sujeto(['We']), verbo([have]), complemento([identified, three, 'CD8+', 'cell-specific', 'DNAase', 'I', hypersensitive, sites, '(', 'HSS)', located, upstream, of, the, murine, 'CD8', alpha, gene])]). relacion([sujeto(['In', vitro, mobility, shift, analysis, of, the, -, 4.0, -, kb, 'HSS', region]), verbo([has]), complemento([revealed, multiple, binding, sites, for, the, 'T', 'cell-restricted', transcription, factor, 'GATA-3'])]). relacion([sujeto(['In', vitro]), verbo([translated]), complemento([murine, 'GATA-3', binds, specifically, to, both, 'CD8', 'GATA', 'sites,', and, coexpression, of, this, factor, in, transient, transfection, assays, transactivates, a, reporter, construct, containing, these, sequences])]). relacion([sujeto(['These', results]), verbo([provide]), complemento([the, first, evidence, for, the, role, of, a, 'T', 'cell-restricted', factor, in, the, regulation, of, either, 'CD8', or, 'CD4', genes])]). relacion([sujeto(['The', 'GATA', '\'', 'zinc-finger\'', transcription, factors, are, thought, to]), verbo([have]), complemento([important, roles, in, the, control, of, hematopoiesis])]). relacion([sujeto(['GATA-1', and, 'GATA-2', are]), verbo([found]), complemento([in, the, 'erythroid,', mast, 'cell,', and, megakaryocytic, 'lineages,', and, 'GATA-3', in, 'T', lymphocytes])]). relacion([sujeto(['GATA-1', is]), verbo([required]), complemento([for, erythroid, development, and, has, recently, been, shown, by, gene, transfer, to, direct, megakaryocytic, differentiation, of, the, primitive, myeloid, cell, line, 416, 'B'])]). relacion([sujeto(['Here', we, show, that, enforced, expression, in, 416, 'B', cells, of, either, the, 'GATA-2', or, 'GATA-3', gene, also]), verbo([induces]), complemento([megakaryocytic, 'differentiation,', as, assessed, by, cellular, 'morphology,', acetylcholinesterase, 'activity,', polyploid, 'DNA', 'content,', and, loss, of, 'Mac-1', expression])]). relacion([sujeto(['Unexpectedly,', the, level, of, endogenous, 'GATA-1', mRNA, had]), verbo([increased]), complemento([20, -, to, 30, -, fold, among, the, 'transfectants,', whereas, that, of, 'GATA-2', mRNA, was, unaltered, and, endogenous, 'GATA-3', transcripts, remained, undetectable])]). relacion([sujeto(['This']), verbo([finding]), complemento([suggests, that, 'GATA-2', and, 'GATA-3', lie, upstream, of, 'GATA-1', in, a, regulatory, hierarchy, and, 'that,', in, 416, 'B', 'cells,', 'GATA-1', may, mediate, the, phenotypic, changes, induced, by, 'GATA-2', or, 'GATA-3'])]). relacion([sujeto(['Furthermore,', 416, 'B', cells, treated, with, the, 'DNA', demethylating, agent, 5, -, azacytidine, underwent, megakaryocytic, differentiation, accompanied, by, a, marked]), verbo([increase]), complemento([in, the, level, of, 'GATA-1', mRNA, but, not, that, of, 'GATA-2', or, 'GATA-3'])]). relacion([sujeto(['These', results, strongly, implicate, 'GATA', factors, in, megakaryocytic, differentiation, and]), verbo([suggest]), complemento(['that,', at, least, for, 416, 'B', 'cells,', 'GATA-1', is, a, dominant, regulator, of, maturation, along, this, lineage])]). relacion([sujeto(['Although', 'GATA-1,', -, 2, ',', and, -, 3]), verbo([have]), complemento([been, shown, to, recognize, a, consensus, sequence, derived, from, regulatory, elements, in, erythroid, 'cell-specific', 'genes,', 'WGATAR', '(', in, which, 'W', indicates, 'A/T', and, 'R', indicates, 'A/G),', the, potential, for, more, subtle, differences, in, the, binding, preferences, of, each, factor, has, not, been, previously, addressed])]). relacion([sujeto(['By', employing, a]), verbo([binding]), complemento([selection, and, polymerase, chain, reaction, amplification, scheme, with, randomized, 'oligonucleotides,', we, have, determined, the, 'binding-site', specificities, of, bacterially, expressed, chicken, 'GATA-1,', -, 2, ',', and, -, 3, transcription, factors])]). relacion([sujeto(['Whereas', all, three, 'GATA', factors]), verbo([bind]), complemento([an, 'AGATAA', erythroid, consensus, motif, with, high, 'affinity,', a, 'second,', alternative, consensus, 'DNA', 'sequence,', 'AGATCTTA,', is, also, recognized, well, by, 'GATA-2', and, 'GATA-3', but, only, poorly, by, 'GATA-1'])]). relacion([sujeto(['These', studies]), verbo([suggest]), complemento([that, all, three, 'GATA', factors, are, capable, of, mediating, transcriptional, effects, via, a, common, erythroid, consensus, 'DNA-binding', motif])]). relacion([sujeto(['Furthermore,', 'GATA-2', and, 'GATA-3,', because, of, their, distinct, expression, patterns, and, broader, 'DNA', recognition, 'properties,', may, be]), verbo([involved]), complemento([in, additional, regulatory, processes, beyond, those, of, 'GATA-1'])]). relacion([sujeto(['The', definition, of, an, alternative, 'GATA-2-GATA-3', consensus, sequence, may, facilitate, the, identification, of, new]), verbo([target]), complemento([genes, in, the, further, elucidation, of, the, roles, that, these, transcription, factors, play, during, development])]). relacion([sujeto(['GATA-binding', proteins, constitute, a, family, of, transcription, factors, that]), verbo([recognize]), complemento([a, target, site, conforming, to, the, consensus, 'WGATAR', '(', 'W', =, 'A', or, 'T', and, 'R', =, 'A', or, 'G)'])]). relacion([sujeto(['Here', we]), verbo([have]), complemento([used, the, method, of, polymerase, chain, 'reaction-mediated', random, site, selection, to, assess, in, an, unbiased, manner, the, 'DNA-binding', specificity, of, 'GATA', proteins])]). relacion([sujeto(['Contrary', to, our, 'expectations,', we, show, that, 'GATA', proteins]), verbo([bind]), complemento([a, variety, of, motifs, that, deviate, from, the, previously, assigned, consensus])]). relacion([sujeto(['Many', of, the, nonconsensus, sequences]), verbo([bind]), complemento([protein, with, high, 'affinity,', equivalent, to, that, of, conventional, 'GATA', motifs])]). relacion([sujeto(['Furthermore,', we]), verbo([provide]), complemento([additional, evidence, for, interaction, of, amino, and, carboxy, fingers, of, 'GATA-1', in, defining, its, binding, site])]). relacion([sujeto(['A', chimeric, protein, containing, the, finger, domain, of, areA, and, the, activation, domains, of, 'GATA-1', is, capable, of]), verbo([activating]), complemento([transcription, in, mammalian, cells, through, 'GATA', motifs])]). relacion([sujeto(['Our', findings]), verbo([suggest]), complemento([a, mechanism, by, which, 'GATA', proteins, might, selectively, regulate, gene, expression, in, cells, in, which, they, are, coexpressed])]). relacion([sujeto(['A', family, of, transcriptional]), verbo([activating]), complemento(['proteins,', the, 'GATA', 'factors,', has, been, shown, to, bind, to, a, consensus, motif, through, a, highly, conserved, 'C4', zinc, finger, 'DNA', binding, domain])]). relacion([sujeto(['One', member, of, this, multigene, 'family,', 'GATA-3,', is, most, abundantly]), verbo([expressed]), complemento([in, 'T', 'lymphocytes,', a, cellular, target, for, human, immunodeficiency, virus, type, 1, '(', 'HIV-1)', infection, and, replication])]). relacion([sujeto(['In', vitro, 'DNase', 'I', footprinting, analysis, revealed, six, 'hGATA-3']), verbo([binding]), complemento([sites, in, the, 'U3', region, '(', the, transcriptional, regulatory, 'domain)', of, the, 'HIV-1', 'LTR'])]). relacion([sujeto(['Introduction', of, the, 'HIV-1', plasmids, in, which, the, 'GATA', sites]), verbo([have]), complemento([been, mutated, into, human, 'T', lymphocytes, also, caused, a, significant, reduction, in, 'LTR-mediated', transcription, at, both, the, basal, level, and, in, '(', 'PHA-', plus, 'PMA-)', stimulated, 'T', cells])]). relacion([sujeto(['These', observations]), verbo([suggest]), complemento([that, in, addition, to, its, normal, role, in, 'T', lymphocyte, gene, 'regulation,', 'hGATA-3', may, also, play, a, significant, role, in, 'HIV-1', transcriptional, activation])]). relacion([sujeto(['Eosinophils']), verbo([express]), complemento([mRNA, for, 'GATA-1,', 'GATA-2,', and, 'GATA-3'])]). relacion([sujeto(['Basophils']), verbo([express]), complemento(['GATA-2', and, 'GATA-3'])]). relacion([sujeto(['Treatment', of, 'HL-60', eosinophilic, sublines, with, either, 'interleukin-5', or, butyric, acid]), verbo([increased]), complemento([the, expression, of, 'GATA-1', mRNA, concomitant, with, the, expression, of, 'eosinophil-specific', 'genes,', whereas, levels, of, 'GATA-2', mRNA, remained, relatively, constant])]). relacion([sujeto(['The', presence, of, mRNA, for, these, proteins, in, eosinophils, and, basophils]), verbo([suggests]), complemento([that, gene, transcription, in, these, lineages, may, be, regulated, by, 'GATA-binding', proteins])]). relacion([sujeto(['When', stably, introduced, into, primary, erythroblasts, or, conditionally, transformed, erythroid, progenitors, 'cells,', exogenous, 'GATA-2/ER']), verbo([promoted]), complemento([proliferation, and, inhibited, terminal, differentiation, in, an, 'estrogen-dependent', manner])]). relacion([sujeto(['These', phenotypic, effects, are, specifically, attributable, to, the, action, of, ectopically]), verbo([expressed]), complemento(['GATA-2/ER', because, erythroblasts, expressing, exogenous, 'GATA-2', are, constitutively, arrested, in, differentiation, and, because, erythroid, progenitors, expressing, either, 'Gal/ER', or, 'GATA-3/ER', do, not, display, a, 'hormone-responsive', block, in, differentiation])]). relacion([sujeto(['Thus,', the, 'GATA-2', transcription, factor, appears, to, play, a, role, in]), verbo([regulating]), complemento([the, 'self-renewal', capacity, of, early, erythroid, progenitor, cells])]). relacion([sujeto(['In', this, study, we, analyzed, the, 'T', cell, 'receptor(TcR)', delta, transcripts]), verbo([expressed]), complemento([by, 'CD3-CD16+', cells, and, we, investigated, whether, these, cells, expressed, the, 'hGATA-3', 'T', cell, transcription, factor, and, the, 'recombination-activating', gene, '(', 'RAG)-1'])]). relacion([sujeto(['Two', unrearranged, 'TcR', delta, transcripts, had, a, size, similar, to, that, of, the, functional, 'TcR', delta, mRNA, '(', 2.3, and, 1.3, 'kb)']), verbo([found]), complemento([in, 'TcR', 'gamma/delta+', 'T', lymphocytes])]). relacion([sujeto(['The', sequence, located, upstream, of, the, 'J', delta, 1, segment, corresponded, to, the, previously]), verbo([reported]), complemento(['germ-line', sequence])]). relacion([sujeto(['The', 'J', delta, 1, segment, was, correctly, spliced, to, 'C', 'delta;', in, addition, the, four, 'C', delta, exons, were]), verbo([found]), complemento([to, be, already, assembled])]). relacion([sujeto(['The', expression, of, 'hGATA-3,', a, 'T', 'cell-specific', factor, known, to, be]), verbo([involved]), complemento([in, the, regulation, of, the, transcription, of, 'TcR', delta, 'locus,', was, analyzed, by, 'Northern', 'blot,', in, cultured, 'NK', cell, population, and, clones, '(', but, not, in, freshly, derived, cell, 'populations)'])]). relacion([sujeto(['All', 'NK', clones, and, cell, lines, studied, were]), verbo([found]), complemento([to, express, 'hGATA-3-specific', 'mRNA,', suggesting, that, 'hGATA-3', may, be, involved, in, the, regulation, of, the, unrearranged, 'TcR', delta, gene, expression, in, 'NK', cells])]). relacion([sujeto(['The', 'GATA', family, of, 'C4', 'zinc-finger', transcription, factors]), verbo([has]), complemento([been, implicated, in, 'tissue-specific', gene, regulation, in, birds, and, mammals])]). relacion([sujeto(['One', of, the, members, of, this, 'family,', 'GATA-3,', is, reportedly]), verbo([expressed]), complemento([specifically, in, the, 'T-cell', 'lineage,', where, it, interacts, with, 'GATA', motifs, in, the, 'TCR-alpha,', 'TCR-beta,', and, 'TCR-delta', 'enhancers,', thereby, controlling, the, 'T-cell', phenotype])]). relacion([sujeto(['To', evaluate, the, differentiation, control, properties, of, 'GATA-3,', we]), verbo([have]), complemento([now, documented, its, expression, pattern, during, lymphoid, differentiation, and, murine, embryogenesis])]). relacion([sujeto(['GATA-3', was, uniquely]), verbo([expressed]), complemento([in, 'T-lineage', lymphocytes, expressing, 'TCR', and, 'CD3', 'genes;', it, was, absent, from, 'TCR/CD3', 'mRNA-negative', prothymocytes, and, from, all, 'B-lineage', cells])]). relacion([sujeto(['These', data]), verbo([provide]), complemento([new, clues, about, the, potential, role, of, 'GATA-3', during, mouse, 'development,', and, will, aid, the, interpretation, of, currently, ongoing, gene, knockout, experiments])]). relacion([sujeto(['The', transcription, factors, 'GATA-1,', 'GATA-2,', and, 'GATA-3', were]), verbo([found]), complemento([to, be, expressed, in, several, mouse, and, rat, mast, cell, lines, that, contain, mast, cell, carboxypeptidase, 'A', '(', 'MC-CPA)', and, other, proteases, in, their, cytoplasmic, granules])]). relacion([sujeto(['GATA-1', mRNA, was, not, detected, in, 'P815', 'cells,', an, immature, mouse, 'mastocytoma-derived', cell, line, that, lacks, 'electron-dense', granules, and]), verbo([has]), complemento([low, levels, of, secretory, granule, proteases])]). relacion([sujeto(['Because', the, 5, '\'', -, flanking, regions, of, the, mouse, and, human, 'MC-CPA', genes, contained, a]), verbo([conserved]), complemento(['GATA-binding', motif, 51, base, pairs, upstream, of, their, translation, initiation, 'sites,', the, ability, of, 'GATA-binding', proteins, to, regulate, the, promoter, activity, of, the, 'MC-CPA', gene, was, examined, in, rat, basophilic, leukemia, 'cells,', mouse, 'P815', 'cells,', and, transfected, mouse, 'P815', cells, that, expressed, 'GATA-1'])]). relacion([sujeto(['In', all, three, mast, cell, 'lines,', the, promoter, activity, of, the, 'MC-CPA', gene, depended, on, the, 'GATA']), verbo([binding]), complemento([site])]). relacion([sujeto(['GATA-1,', 'GATA-2,', and, 'GATA-3', are, thus, the, first, 'DNA-binding', proteins, identified, in, mast, cells, which]), verbo([regulate]), complemento([the, promoter, activity, of, a, gene, that, encodes, a, secretory, granule, protease])]). relacion([sujeto(['Proteins', that]), verbo([recognize]), complemento([the, core, sequence, 'GATA', are, important, regulators, of, 'hematopoietic-specific', gene, transcription])]). relacion([sujeto(['We']), verbo([have]), complemento([characterized, cDNAs, encoding, the, 'Xenopus', laevis, homologues, of, three, related, transcription, 'factors,', designated, 'GATA-1,', -, 2, ',', and, -, 3])]). relacion([sujeto(['Comparative', sequence, analysis]), verbo([reveals]), complemento([strong, conservation, of, the, 'zinc-finger', 'DNA-binding', domain, among, all, vertebrate, 'GATA-binding', proteins])]). relacion([sujeto(['GATA-2', and, 'GATA-3', polypeptides, are, homologous, throughout, their, entire, 'sequences,', whereas, 'GATA-1', sequence, is]), verbo([conserved]), complemento([only, in, the, region, responsible, for, 'DNA', binding])]). relacion([sujeto(['In', 'Xenopus,', 'RNAs', encoding, 'GATA-binding', proteins, are]), verbo([expressed]), complemento([in, both, larval, and, adult, erythroid, cells])]). relacion([sujeto(['To']), verbo([find]), complemento([a, common, 'TCR', regulatory, 'element,', we, have, studied, the, ability, of, the, newly, described, 'enhancer-binding', protein, 'Gata3', to, bind, to, the, sequence, motif, '(', 'A/T)GATA(G/A)', shared, between, enhancer, elements, of, all, four, 'TCR', genes])]). relacion([sujeto(['We']), verbo([have]), complemento([isolated, a, 'full-length', human, 'Gata3', cDNA, and, characterized, its, role, in, 'TCR', gene, regulation])]). relacion([sujeto(['The', in, vitro]), verbo([transcribed]), complemento([and, translated, 'Gata3', cDNA, product, bound, specifically, to, the, enhancer, elements, of, at, least, three, 'TCR', genes, containing, the, above, consensus, sequence])]). relacion([sujeto(['This']), verbo([binding]), complemento([specificity, was, consistent, with, the, in, vivo, activity, of, the, 'TCR', 'enhancer-binding', element, in, transient, transfection, assays])]). relacion([sujeto(['A', family, of, transcriptional, activators]), verbo([has]), complemento([recently, been, identified, in, 'chickens;', these, transcriptional, activators, recognize, a, common, consensus, motif, '(', 'WGATAR)', through, a, conserved, 'C4', zinc, finger, 'DNA-binding', domain])]). relacion([sujeto(['One', of, the, members, of, this, multigene, 'family,', 'cGATA-3,', is, most, abundantly]), verbo([expressed]), complemento([in, the, 'T-lymphocyte', cell, lineage])]). relacion([sujeto(['The', murine, and, human, factors, are, abundantly]), verbo([expressed]), complemento([in, a, variety, of, human, and, murine, 'T-cell', lines, and, can, activate, transcription, through, a, 'tissue-specific', 'GATA-binding', site, identified, within, the, human, 'T-cell', receptor, delta, gene, enhancer])]). relacion([sujeto(['We', infer, that, the, murine, and, human, 'GATA-3', proteins, play, a, central, and, highly]), verbo([conserved]), complemento([role, in, vertebrate, 'T-cell-specific', transcriptional, regulation])]). relacion([sujeto(['Nuclear', cap]), verbo([binding]), complemento([protein, complex, '(', 'CBC)', is, a, heterodimer, of, a, small, subunit, '(', 'Cbc2', in, 'yeast)', that, binds, the, 'm(7)G', cap, and, a, large, subunit, '(', 'Sto1', in, 'yeast)', that, interacts, with, karyopherins])]). relacion([sujeto(['These', lesions, had, no, effect, on, vegetative, 'growth,', but, they, ameliorated, the, 'cold-sensitivity', of, tgs1Δ, cells, that, lack, trimethylguanosine, caps, '(', a, phenotype, attributed, to, ectopic, association, of, 'CBC', with, the, 'm(7)G', cap, of, the, normally, 'TMG-capped', 'U1', 'snRNA),', thereby, attesting, to, their, impact, on, cap]), verbo([binding]), complemento([in, vivo])]). relacion([sujeto(['Further', studies, of, the, 'Cbc2-Y24A', variant, revealed, synthetic, lethality, or, sickness, with, null, mutations, of, proteins]), verbo([involved]), complemento([in, early, steps, of, spliceosome, assembly, '(', 'Nam8,', 'Mud1,', 'Swt21,', 'Mud2,', 'Ist3,', and, 'Brr1)', and, with, otherwise, benign, mutations, of, 'Msl5,', the, essential, branchpoint, binding, protein])]). relacion([sujeto(['Whereas', the, effects, of, weakening, 'CBC-cap', interactions, are, buffered, by, other, actors, in, the, splicing, pathway, during, mitotic, 'growth,', the, 'NΔ42', allele]), verbo([causes]), complemento([a, severe, impediment, to, yeast, sporulation, and, meiosis])]). relacion([sujeto(['These', studies]), verbo([reveal]), complemento([a, new, level, of, splicing, control, during, meiosis, that, is, governed, by, nuclear, 'CBC'])]). relacion([sujeto(['The', highly]), verbo([conserved]), complemento(['Saccharomyces', cerevisiae, 'cap-binding', protein, 'Cbc1/Sto1', binds, mRNA, 'co-transcriptionally', and, acts, as, a, key, coordinator, of, mRNA, fate])]). relacion([sujeto(['Recently,', 'Cbc1']), verbo([has]), complemento([also, been, implicated, in, transcription, elongation, and, 'pre-initiation', complex, '(', 'PIC)', formation])]). relacion([sujeto(['Previously,', we, described, 'Cbc1', to, be]), verbo([required]), complemento([for, cell, growth, under, osmotic, stress, and, to, mediate, 'osmostress-induced', translation, reprogramming])]). relacion([sujeto(['Additionally,', 'CBC1', deletion, specifically, reduces, transcription, rates, of, highly]), verbo([transcribed]), complemento([genes, under, 'non-stress', 'conditions,', such, as, ribosomal, protein, '(', 'RP)', 'genes,', while, having, low, impact, on, transcription, of, weakly, expressed, genes])]). relacion([sujeto(['Altogether,', our, results, indicate, that]), verbo([binding]), complemento([of, 'Cbc1', to, the, capped, mRNAs, is, necessary, for, the, accumulation, of, specific, activators, as, well, as, 'PIC', components, at, the, promoters, of, genes, whose, expression, requires, high, and, rapid, transcription])]). relacion([sujeto(['The', use, of, gene, manipulation, for]), verbo([increased]), complemento([tolerance, to, abiotic, stress, has, been, successful, in, many, plant, species])]). relacion([sujeto(['Overexpression', of, the, 'Arabidopsis', 'SALT', 'TOLERANT1', '(', 'STO1)', gene]), verbo([leads]), complemento([to, increased, concentrations, of, 9, -, 'cis-epoxycarotenoid', 'dioxygenase3,', a, vital, enzyme, in, 'Arabidopsis', abscisic, acid, biosynthesis])]). relacion([sujeto(['In', the, present, 'work,', the, 'Arabidopsis', 'STO1', gene, '(', 'AtSTO1)', was, overexpressed, in, poplar, to, determine, if, the, transgene, would]), verbo([confer]), complemento([enhanced, salt, tolerance, to, the, generated, transgenics])]). relacion([sujeto(['Phytophthora', 'infestans,']), verbo([causing]), complemento([late, blight, in, 'potato,', remains, one, of, the, most, devastating, pathogens, in, potato, production, and, late, blight, resistance, is, a, top, priority, in, potato, breeding])]). relacion([sujeto(['Cisgenesis', is, a, promising, approach, that, introduces, native, genes, from, the, crops, own, gene, pool, using, 'GM', 'technology,', thereby]), verbo([retaining]), complemento([favourable, characteristics, of, established, varieties])]). relacion([sujeto(['Through', further, analyses]), verbo([involving]), complemento([morphological, evaluations, in, the, 'greenhouse,', responsiveness, to, 'Avr', genes, and, late, blight, resistance, in, detached, leaf, 'assays,', the, selection, was, narrowed, down, to, eight, independent, events])]). relacion([sujeto(['We', developed, a, 'marker-free', transformation, pipeline, to, select, potato, plants, functionally]), verbo([expressing]), complemento([a, stack, of, late, blight, 'R', genes])]). relacion([sujeto(['Thereby,', this, study]), verbo([provides]), complemento([an, important, tool, for, the, successful, deployment, of, 'R', genes, in, agriculture, and, contributes, to, the, production, of, potentially, durable, late, blight, resistant, potatoes])]). relacion([sujeto(['In', the, 'Paramecium', 'genome,', we]), verbo([found]), complemento([only, 'Stomatins,', 20, paralogs, grouped, in, 8, 'families,', 'STO1', to, 'STO8'])]). relacion([sujeto(['With', all, family, members, 'tested,', we]), verbo([found]), complemento([a, patchy, localization, 'at/near', the, cell, surface, and, on, vesicles])]). relacion([sujeto(['The', 'Sto1p', and, 'Sto4p', families, are, also]), verbo([associated]), complemento([with, the, contractile, vacuole, complex])]). relacion([sujeto(['Sto4p', also, makes, puncta, on, some, food, vacuoles, and, is, abundant, on, vesicles, recycling, from, the]), verbo([release]), complemento([site, of, spent, food, vacuoles, to, the, site, of, nascent, food, vacuole, formation])]). relacion([sujeto(['Silencing', of, the, 'STO1', family, reduces, mechanosensitivity, '(', ciliary, reversal, upon, touching, an, 'obstacle),', thus]), verbo([suggesting]), complemento([relevance, for, positioning, of, mechanosensitive, channels, in, the, plasmalemma])]). relacion([sujeto(['Silencing', of, 'STO4', members]), verbo([increases]), complemento([pulsation, frequency, of, the, contractile, vacuole, complex, and, reduces, phagocytotic, activity, of, 'Paramecium', cells])]). relacion([sujeto(['In', 'summary,', 'Sto1p', and, 'Sto4p', members, seem, to, be]), verbo([involved]), complemento([in, positioning, specific, superficial, and, intracellular, 'microdomain-based', membrane, components, whose, functions, may, depend, on, mechanosensation, '(', extracellular, stimuli, and, internal, osmotic, 'pressure)'])]). relacion([sujeto(['These', include, the, overproduction, of, the, exopolysaccharide, alginate, and, the]), verbo([loss]), complemento([of, complete, lipopolysaccharide, '(', 'LPS)'])]). relacion([sujeto(['When', grown, at, 25, °, 'C,', 2192]), verbo([expresses]), complemento([serotype, 'O1', 'LPS', with, a, moderate, chain, length, and, in, reduced, amounts, relative, to, those, of, a, 'wild-type', serotype, 'O1', laboratory, strain, '(', 'stO1)'])]). relacion([sujeto(['In', 'contrast,', 2192]), verbo([expresses]), complemento([no, 'LPS', 'O', antigen, when, grown, at, 37, °, 'C'])]). relacion([sujeto(['This', is, the, first, time, that, a, 'temperature-sensitive', defect, in, 'O-antigen', production]), verbo([has]), complemento([been, reported])]). relacion([sujeto(['Using', complementation, analyses, with, a, constructed, wbpM, deletion, mutant, of, 'stO1,', we, demonstrate, that, the, 'temperature-sensitive', 'O-antigen', production, defect, in, 2192, is, due, to, a, mutation, in, 'wbpM,', which, encodes, a, 'UDP-4,6-GlcNAc', dehydratase]), verbo([involved]), complemento([in, 'O-antigen', synthesis])]). relacion([sujeto(['This', residue, of, 'WbpM,', which, is, critical, for, stability, and, 'function,', is, located, outside, of, the]), verbo([recognized]), complemento([domains, of, the, protein, and, may, provide, insight, into, the, 'structure-function', relationship, of, this, 'enzyme,', which, is, found, in, all, 20, serotypes, of, 'P'])]). relacion([sujeto(['We', also, identify, a, promoter, of, 'wbpM,', map, a, transcriptional, start, site, of, 'wbpM,', and, show, that, mucoidy, plays, a, role, in, the]), verbo([loss]), complemento([of, expression, of, 'high-molecular-weight', 'LPS', in, this, 'CF', isolate])]). relacion([sujeto(['Here,', we, show, that, potato, '(', 'Solanum', 'tuberosum)', resistance, protein, 'R3a', relocates, from, the, cytoplasm, to, endosomal, compartments, only, when, coexpressed, with]), verbo([recognized]), complemento(['Phytophthora', infestans, effector, form, 'AVR3a(KI)', and, not, unrecognized, form, 'AVR3a(EM)'])]). relacion([sujeto(['No', such, effect, of, these, inhibitors, was, observed, on, 'HRs']), verbo([triggered]), complemento([by, the, 'gene-for-gene', pairs, 'Rx1/PVX-CP', and, 'Sto1/IpiO1'])]). relacion([sujeto(['An', 'R3a(D501V)', autoactive, 'MHD', 'mutant,', which]), verbo([triggered]), complemento(['HR', in, the, absence, of, 'AVR3a(KI),', failed, to, localize, to, endosomes])]). relacion([sujeto(['Moreover,', 'BFA', and, wortmannin, did, not, alter, cell, death]), verbo([triggered]), complemento([by, this, mutant])]). relacion([sujeto(['We', conclude, that, effector, recognition, and, consequent, 'HR', signaling, by, 'NB-LRR', resistance, protein, 'R3a']), verbo([require]), complemento([its, relocalization, to, vesicles, in, the, endocytic, pathway])]). relacion([sujeto(['Shortening', eukaryotic, 'poly(A)', tails, represses, mRNA, translation, and]), verbo([induces]), complemento([mRNA, turnover])]). relacion([sujeto(['The', major, cytoplasmic, 'deadenylase,', the, 'Ccr4-Not', 'complex,', is, a]), verbo([conserved]), complemento([multisubunit, assembly])]). relacion([sujeto(['Ccr4-Not', is, organized, around, 'Not1,', a, large, scaffold, protein, that]), verbo([recruits]), complemento([two, 3, '\'', -, 5, '\'', 'exoribonucleases,', 'Caf1', and, 'Ccr4'])]). relacion([sujeto(['We']), verbo([report]), complemento([structural, studies, showing, that, the, 'N-terminal', arm, of, yeast, 'Not1', has, a, 'HEAT-repeat', structure, with, domains, related, to, the, 'MIF4G', fold])]). relacion([sujeto(['A', 'MIF4G', domain, positioned, centrally, within, the, 'Not1', protein]), verbo([recognizes]), complemento(['Caf1,', which, in, turn, binds, the, 'LRR', domain, of, 'Ccr4', and, tethers, the, 'Ccr4', nuclease, domain])]). relacion([sujeto(['In', response, to, osmotic, 'stress,', global, translation, is, 'inhibited,', but, the, mRNAs, encoding, 'stress-protective', proteins, are, selectively]), verbo([translated]), complemento([to, allow, cell, survival])]). relacion([sujeto(['To', 'date,', the, mechanisms, and, factors]), verbo([involved]), complemento([in, the, specific, translation, of, 'osmostress-responsive', genes, in, 'Saccharomyces', cerevisiae, are, unknown])]). relacion([sujeto(['We']), verbo([find]), complemento([that, the, mRNA, 'cap-binding', protein, 'Cbc1', is, important, for, yeast, survival, under, osmotic, stress])]). relacion([sujeto(['Our', results]), verbo([provide]), complemento([new, evidence, supporting, a, role, of, 'Cbc1', in, translation, initiation])]). relacion([sujeto(['Cbc1']), verbo([associates]), complemento([with, 'polysomes,', while, the, deletion, of, the, 'CBC1', gene, causes, hypersensitivity, to, the, translation, inhibitor, cycloheximide, and, yields, synthetic, &, 'quot;sickness"', in, cells, with, limiting, amounts, of, translation, initiator, factor, eIF4E])]). relacion([sujeto(['Furthermore,', 'osmostress-responsive', mRNAs, are, transcriptionally]), verbo([induced]), complemento([after, osmotic, stress, in, cbc1Δ, 'cells,', but, their, rapid, association, with, polysomes, is, delayed])]). relacion([sujeto(['However,', in, cells, containing, a, thermosensitive, eIF4E, 'allele,', their, inability, to, grow, at, 37, º, 'C', is]), verbo([suppressed]), complemento([by, 'hyperosmosis,', and, 'Cbc1', relocalizes, from, nucleus, to, cytoplasm])]). relacion([sujeto(['Small']), verbo([nuclear]), complemento([and, nucleolar, 'RNAs', that, program, 'pre-mRNA', splicing, and, rRNA, processing, have, a, signature, 5, '\'', -, trimethylguanosine, '(', 'TMG)', cap])]). relacion([sujeto(['Whereas', the, mechanism, of, 'TMG', synthesis, by, 'Tgs1', methyltransferase]), verbo([has]), complemento([been, 'elucidated,', we, know, little, about, whether, or, how, 'RNP', 'biogenesis,', structure, and, function, are, perturbed, when, 'TMG', caps, are, missing])]). relacion([sujeto(['Finer', analysis, revealed, stoichiometric, association, of, the]), verbo([nuclear]), complemento(['cap-binding', protein, '(', 'CBP)', subunits, 'Sto1', and, 'Cbc2', with, otherwise, intact, 'Mud1-', and, 'Nam8-containing', 'U1', snRNPs, from, tgs1Δ, cells])]). relacion([sujeto(['Moreover,', 'CBP', was, not]), verbo([associated]), complemento([with, mature, 'Nop58-containing', 'C/D', snoRNPs, or, mature, 'Cbf5-', and, 'Gar1-containing', 'H/ACA', snoRNPs, from, tgs1Δ, cells])]). relacion([sujeto(['The', 'cold-sensitive', '(', 'cs)', growth, defect, of, tgs1Δ, yeast, cells, could, be]), verbo([suppressed]), complemento([by, mutating, the, 'cap-binding', pocket, of, 'Cbc2,', suggesting, that, ectopic, 'CBP', binding, to, the, exposed, 'U1', 'm(7)G', cap, in, tgs1Δ, cells, '(', not, lack, of, 'TMG', caps, per, 'se)', underlies, the, cs, phenotype])]). relacion([sujeto(['Functional', stacking, of, broad, spectrum, resistance, '(', 'R)', genes, could, potentially, be, an, effective, strategy, for, more, durable, disease, 'resistance,', for, 'example,', to, potato, late, blight]), verbo([caused]), complemento([by, 'Phytophthora', infestans, '(', 'Pi)'])]). relacion([sujeto(['bulbocastanum)', were, 'selected,', combined, into, a, single, binary, vector, pBINPLUS, and, transformed, into, the, susceptible]), verbo([cultivar]), complemento(['Desiree'])]). relacion([sujeto(['No', indications, were]), verbo([found]), complemento([for, silencing, or, any, other, negative, effects, affecting, the, function, of, the, inserted, 'Rpi', genes])]). relacion([sujeto(['While', splicing, repressors, typically, interfere, with, transcript, recognition, by, spliceosomal, 'components,', the, yeast, protein, 'L30', blocks, spliceosomal, rearrangements]), verbo([required]), complemento([for, the, engagement, of, 'U2', snRNP, '(', small, ribonucleoprotein, 'particle)', to, its, own, transcript, 'RPL30'])]). relacion([sujeto(['Using', a, mutation, in, the, 'RPL30']), verbo([binding]), complemento([site, that, disrupts, this, 'repression,', we, have, taken, a, genetic, approach, to, reveal, that, regulation, of, splicing, is, restored, in, this, mutant, by, deletion, of, the, 'cap-binding', complex, '(', 'CBC)', component, 'Cbp80'])]). relacion([sujeto(['It']), verbo([promotes]), complemento([the, initial, 5, '\'', splice, site, recognition, by, 'U1', 'and,', 'independently,', facilitates, 'U2', 'recruitment,', depending, on, sequences, located, in, the, vicinity, of, the, 5, '\'', splice, site])]). relacion([sujeto(['These', results]), verbo([reveal]), complemento([a, novel, function, for, 'CBC', in, splicing, and, imply, that, these, molecular, events, can, be, the, target, of, a, splicing, regulator])]). relacion([sujeto(['One', protein, complex, that, is, intimately]), verbo([involved]), complemento([in, 'pre-mRNA', 'splicing,', the, yeast, 'cap-binding', 'complex,', appears, to, be, particularly, 'important,', as, evidenced, by, its, extensive, and, unique, genetic, interactions, with, enzymes, that, catalyze, histone, 'H2B', ubiquitination])]). relacion([sujeto(['Microarray', studies, show, that, cap]), verbo([binding]), complemento([complex, '(', 'CBC)', deletion, has, a, global, effect, on, gene, 'expression,', and, for, approximately, 20, '%', of, these, 'genes,', this, effect, is, suppressed, when, ubiquitination, of, histone, 'H2B', is, eliminated])]). relacion([sujeto(['Consistent', with, this]), verbo([finding]), complemento([of, histone, 'H2B', dependent, effects, on, gene, 'expression,', deletion, of, the, yeast, cap, binding, complex, leads, to, overubiquitination, of, histone, 'H2B'])]). relacion([sujeto(['A', key, component, of, the, 'ubiquitin-protease', module, of, the, 'SAGA', 'complex,', 'Sus1,', is, encoded, by, a, gene, that, contains, two, introns, and, is, misspliced, when, the, 'CBC', is, 'deleted,']), verbo([leading]), complemento([to, destabilization, of, the, ubiquitin, protease, complex, and, defective, modulation, of, cellular, 'H2B', levels])]). relacion([sujeto(['These', data, demonstrate, that, 'pre-mRNA', splicing, plays, a, critical, role, in, histone, 'H2B', ubiquitination, and, that, the, 'CBC', in, particular, helps, to, establish, the, proper, state, of, chromatin, and, proper, expression, of, genes, that, are]), verbo([regulated]), complemento([at, the, level, of, histone, 'H2B', ubiquitination])]). relacion([sujeto(['To', understand, how, 'DEXD/H-box', proteins]), verbo([recognize]), complemento([and, interact, with, their, cellular, 'substrates,', we, have, been, studying, 'Prp28p,', a, 'DEXD/H-box', splicing, factor, required, for, switching, the, 'U1', snRNP, with, the, 'U6', snRNP, at, the, precursor, mRNA, '(', 'pre-mRNA)', 5, '\'', splice, site])]). relacion([sujeto(['We', previously, demonstrated, that, the, requirement, for, 'Prp28p', can, be, eliminated, by, mutations, that, alter, either, the, 'U1', snRNA, or, the, 'U1C', 'protein,']), verbo([suggesting]), complemento([that, both, are, targets, of, 'Prp28p'])]). relacion([sujeto(['Inspired', by, this, 'finding,', we, designed, a, bypass, genetic, screen, to, specifically, search, for, 'additional,', novel]), verbo([targets]), complemento([of, 'Prp28p'])]). relacion([sujeto(['Our', data]), verbo([suggest]), complemento([that, 'Ynl187p', acts, in, concert, with, 'U1C', and, 'Cbp80p', to, help, stabilize, the, 'U1', 'snRNP-5\'', splice, site, interaction])]). relacion([sujeto(['The', levels, of, soluble, 'sugars,', such, as, glucose, and, 'sucrose,', help]), verbo([regulate]), complemento([many, plant, 'metabolic,', physiological, and, developmental, processes])]). relacion([sujeto(['Genetic', screens, are, helping, identify, some, of, the, loci]), verbo([involved]), complemento([in, plant, sugar, response, and, reveal, extensive, 'cross-talk', between, sugar, and, phytohormone, response, pathways])]). relacion([sujeto(['A', forward, genetic, screen, was, performed, to, identify, mutants, with]), verbo([increased]), complemento([resistance, to, the, inhibitory, effects, of, high, levels, of, exogenous, sugars, on, early, 'Arabidopsis', seedling, development])]). relacion([sujeto(['The', positional, cloning, and, characterization, of, two, of, these, sugar, insensitive, '(', 'sis)', 'mutants,', both, of, which, are, also]), verbo([involved]), complemento([in, abscisic, acid, '(', 'ABA)', biosynthesis, or, 'response,', are, reported])]). relacion([sujeto(['Gene', expression, profiling, revealed, that, a, significant, number, of, genes, that, are]), verbo([expressed]), complemento([at, lower, levels, in, germinating, 'sis7-1/nced3-4/sto1-4', seeds, than, in, 'wild-type', seeds, are, implicated, in, auxin, biosynthesis, or, 'transport,', suggesting, 'cross-talk', between, 'ABA', and, auxin, response, pathways])]). relacion([sujeto(['Mutations', in, the, 'SIS7/NCED3/STO1', 'gene,', which, is, primarily]), verbo([required]), complemento([for, 'ABA', biosynthesis, under, drought, 'conditions,', confer, a, 'sugar-insensitive', 'phenotype,', indicating, that, a, constitutive, role, in, 'ABA', biosynthesis, is, not, necessary, to, confer, sugar, insensitivity])]). relacion([sujeto(['Findings', presented, here, clearly, demonstrate, that, mutations, in, 'ABI3', can]), verbo([confer]), complemento([a, 'sugar-insensitive', phenotype, and, help, explain, 'previous,', mixed, reports, on, this, topic, by, showing, that, 'ABA', and, sugar, insensitivity, exhibit, a, strong, positive, correlation, in, different, abi3, mutants])]). relacion([sujeto(['Potato', is, the, 'world\'s', fourth, largest, food, crop, yet, it, continues, to, endure, late, 'blight,', a, devastating, disease]), verbo([caused]), complemento([by, the, 'Irish', famine, pathogen, 'Phytophthora', infestans])]). relacion([sujeto(['The', 'RXLR', effector, family, 'IpiO']), verbo([induced]), complemento([hypersensitive, responses, '(', 'HR)', in, 'S'])]). relacion([sujeto(['A', candidate, gene, approach]), verbo([led]), complemento([to, the, rapid, cloning, of, 'S'])]). relacion([sujeto(['Highly']), verbo([conserved]), complemento(['RGA1-blb', homologues, were, discovered, in, all, the, tested, 'tuber-bearing', '(', 'TB)', and, 'non-tuber-bearing', '(', 'NTB)', 'Solanum', 'species,', suggesting, 'RGA1-blb', was, present, before, the, divergence, of, 'TB', and, 'NTB', 'Solanum', species])]). relacion([sujeto(['Interestingly,', highly]), verbo([conserved]), complemento(['Rpi-blb1', homologues, were, discovered, not, only, in, 'S'])]). relacion([sujeto(['Resistance', assays, and, genetic, analyses, in, several, 'F1', populations, derived, from, the, relevant, late, blight, resistant, parental, genotypes, harbouring, the]), verbo([conserved]), complemento(['Rpi-blb1', 'homologues,', indicated, the, presence, of, four, dominant, 'R', 'genes,', designated, as, 'Rpi-sto1,', 'Rpi-plt1,', 'Rpi-pta1', and, 'Rpi-pta2'])]). relacion([sujeto(['Hypotheses', are, proposed, to, explain, the, presence, of]), verbo([conserved]), complemento(['Rpi-blb1', homologues, in, 'S'])]). relacion([sujeto(['The', discovery, of]), verbo([conserved]), complemento([homologues, of, 'Rpi-blb1', in, 'EBN', 2, tetraploid, species, offers, the, possibility, to, more, easily, transfer, the, late, blight, resistance, genes, to, potato, varieties, by, classical, breeding])]). relacion([sujeto(['The', study, of, the, dynamic, interactome, of, cellular, ribonucleoprotein, '(', 'RNP)', particles]), verbo([has]), complemento([been, hampered, by, severe, methodological, limitations])]). relacion([sujeto(['In', 'particular,', the, affinity, purification, of, intact, 'RNP', complexes, from, cell, lysates, suffers, from, 'RNA', 'degradation,']), verbo([loss]), complemento([of, interacting, macromolecules, and, poor, overall, yields])]). relacion([sujeto(['We', previously, demonstrated, that, mRNAs]), verbo([retained]), complemento([in, the, nucleus, of, 'Saccharomyces', cerevisiae, are, subjected, to, a, degradation, 'system-designated', 'DRN', '(', degradation, of, mRNA, in, the, 'nucleus),', that, is, diminished, in, 'cbc1-Delta', or, 'cbc2-Delta', mutants, lacking, components, of, the, 'cap-binding', complex, and, in, 'rrp6-Delta', mutants, lacking, 'Rrp6p,', a, 3, '\'', to, 5, '\'', nuclear, exonuclease])]). relacion([sujeto(['LYS2', mRNAs, from, the, 'lys2-187', and, related, mutants, were, rapidly, 'degraded,', and, the, degradation, was]), verbo([suppressed]), complemento([by, 'cbc1-Delta', and, 'rrp6-Delta'])]). relacion([sujeto(['The', 'U1A-GFP', imaging, procedure, was, used, to, show, that, the, 'lys2-187', mRNA, was, partially]), verbo([retained]), complemento([in, the, 'nucleus,', explaining, the, susceptibility, to, 'DRN'])]). relacion([sujeto(['The', creation, of, several, derivatives, of, 'lys2-187', by, 'site-directed', mutagenesis, revealed, that, the, 'in-frame', 'TGA', by, itself, was, not, responsible, for, the]), verbo([increased]), complemento([susceptibility, to, 'DRN'])]). relacion([sujeto(['Furthermore,', this, &, 'quot;retention', 'signal"']), verbo([causing]), complemento([susceptibility, to, 'DRN', is, lost, by, altering, one, of, the, base, 'pairs,', establishing, that, mRNAs, susceptible, and, unsusceptible, to, 'DRN', can, be, attributed, to, a, single, nucleotide, in, the, proper, context])]). relacion([sujeto(['We', previously, demonstrated, an]), verbo([increased]), complemento([degradation, of, mRNAs, in, mutants, of, 'Saccharomyces', cerevisiae, having, blocks, in, nuclear, export])]). relacion([sujeto(['The', degradation, 'activity,', designated, 'DRN', '(', degradation, of, mRNA, in, the, 'nucleus),']), verbo([requires]), complemento(['Cbc1p,', a, nuclear, 'cap-binding', 'protein,', and, 'Rrp6p,', a, nuclear, exosome, component])]). relacion([sujeto(['Microarray', procedures, were, used, to, determine, the, 'half-lives', of, mRNAs, from, normal, and, mutant, 'strains,']), verbo([leading]), complemento([to, the, tentative, identification, of, hundreds, of, normal, mRNAs, that, were, notably, stabilized, when, either, 'CBC1', or, 'RRP6', were, deleted])]). relacion([sujeto(['One', representative, of, this, 'group,', 'SKS1', 'mRNA,', was, also, shown, by, a, cytological, procedure, to, be, preferentially]), verbo([retained]), complemento([in, the, nucleus, compared, with, typical, mRNAs])]). relacion([sujeto(['We']), verbo([suggest]), complemento([that, all, normal, mRNAs, are, subjected, to, degradation, by, 'DRN,', but, the, degree, of, degradation, is, determined, by, the, degree, of, nuclear, retention])]). relacion([sujeto(['This', conclusion, was, corroborated, by]), verbo([finding]), complemento([an, inverse, relationship, of, the, 'CBC1', and, 'SKS1', mRNA, levels, in, normal, strains, grown, under, different, conditions])]). relacion([sujeto(['We']), verbo([have]), complemento([identified, a, 'T-DNA', insertion, mutation, of, 'Arabidopsis', '(', ecotype, 'C24),', named, sto1, '(', salt, 'tolerant),', that, results, in, enhanced, germination, on, both, ionic, '(', 'NaCl)', and, nonionic, '(', 'sorbitol)', hyperosmotic, media])]). relacion([sujeto(['Improved', growth, of, sto1, mutant, plants, on, 'NaCl,', but, not, 'sorbitol,', medium, was]), verbo([associated]), complemento([with, a, reduction, in, both, 'NaCl-induced', expression, of, the, 'ICK1', gene, and, ethylene, accumulation])]). relacion([sujeto(['The', sto1, mutation]), verbo([has]), complemento([revealed, that, reduced, 'ABA', can, lead, to, more, rapid, growth, during, hyperionic, stress, by, a, signal, pathway, that, apparently, is, at, least, partially, independent, of, signals, that, mediate, nonionic, osmotic, responses])]). relacion([sujeto(['We', cloned, 'PsSTO1,', which, encodes, the, 'SHAM-sensitive', terminal, oxidase, '(', 'PsSto1p),', by, genome, walking, from, 'wild-type', 'CBS', 6054, and, subsequently, deleted, 'PsSTO1', by]), verbo([targeted]), complemento([gene, disruption])]). relacion([sujeto(['Heterologous', expression, of, 'PsSTO1', in, 'Saccharomyces', cerevisiae]), verbo([increased]), complemento([its, total, oxygen, consumption, rate, and, imparted, 'cyanide-resistant', oxygen, uptake, but, did, not, enable, growth, on, 'ethanol,', indicating, that, 'PsSto1p', is, not, coupled, to, 'ATP', synthesis])]). relacion([sujeto(['Unexpectedly,', deleting, 'PsSto1p']), verbo([led]), complemento([to, the, use, of, 'Complex', 'I', in, the, mutant, cells, when, xylose, was, the, carbon, source])]). relacion([sujeto(['We']), verbo([have]), complemento([taken, advantage, of, the, excellent, cytology, available, in, 'S'])]). relacion([sujeto([pombe, to, examine, the, phenotypic, consequences, of, a, deletion, of, 'sto1(+),', a, gene, that, encodes, a, protein, similar, to, 'Cofactor', 'E,', which, is]), verbo([required]), complemento([for, the, folding, of, 'alpha-tubulin'])]). relacion([sujeto(['After', a, transient]), verbo([arrest]), complemento([with, condensed, 'chromosomes,', the, cells, exit, mitosis, and, resume, 'DNA', 'synthesis,', whereupon, they, septate, abnormally, and, die])]). relacion([sujeto(['Unlike', its, presumptive, partner, 'Cofactor', 'D', '(', 'Alp1p),', 'however,', 'Sto1p', does, not, localize, to, microtubules, but, is]), verbo([found]), complemento([throughout, the, cell])]). relacion([sujeto(['Overexpression', of, 'Sto1p']), verbo([has]), complemento([no, toxic, effects, in, 'wild-type', 'cells,', suggesting, that, it, is, unable, to, disrupt, 'alpha/beta', tubulin, dimers, in, vivo])]). relacion([sujeto(['To', study, the, function, of, 'GCR3,', a, gene]), verbo([involved]), complemento([in, the, expression, of, glycolytic, genes, in, 'Saccharomyces', 'cerevisiae,', a, 'Candida', albicans, gene, which, complements, the, growth, defect, of, the, '(', 'delta)gcr3', mutant, was, isolated])]). relacion([sujeto(['DNA', sequencing, showed, it, to, be, 'GCR3,', a, gene]), verbo([involved]), complemento([in, the, expression, of, glycolytic, genes])]). relacion([sujeto(['Further', analysis, showed, that, gcr3, mutations, also]), verbo([suppressed]), complemento([the, 'temperature-sensitive', growth, of, hpr1, single, mutants])]). relacion([sujeto(['Experiments', with, gcr3, truncation, mutants, also]), verbo([suggested]), complemento([a, genetic, interaction, between, 'GCR3', and, 'HPR1'])]). relacion([sujeto(['The', fact, that, top1]), verbo([suppressed]), complemento([the, growth, defect, of, gcr3, suggested, an, interaction, between, those, two, genes, also])]). relacion([sujeto(['Plasmid', 'DNA', isolated, from, gcr3, mutants, was, significantly, more, negatively, supercoiled, than, 'normal,']), verbo([suggesting]), complemento([that, 'Gcr3', 'protein,', like, topoisomerase, 'I', and, 'Hpr1p,', affects, chromatin, 'structure,', perhaps, during, transcription])]). relacion([sujeto(['G4', nucleic, acids, are, quadruplex, structures]), verbo([involving]), complemento(['guanine-rich', sequences, that, form, in, vitro, under, moderate, conditions])]). relacion([sujeto(['Experimental', evidence, exists, supporting, biological, functions, for, these, 'elements;', 'however,', direct, demonstration, of, 'G4', nucleic, acids, in, vivo]), verbo([has]), complemento([not, yet, been, achieved])]). relacion([sujeto(['Here', we, purify, and, characterize, a, yeast, 'protein,', 'G4p2,', which]), verbo([has]), complemento([a, specific, affinity, for, 'G4', nucleic, acids])]). relacion([sujeto(['G4p2']), verbo([binds]), complemento([equivalently, to, 'RNA', and, 'DNA', in, 'G4', form])]). relacion([sujeto(['The', 'Keq', for, 'G4p2']), verbo([binding]), complemento([to, a, 'G4', 'DNA', oligomer, is, 2.2, x, 10, '(', 8, ')', 'M-1', under, near, physiological, conditions])]). relacion([sujeto(['We']), verbo([have]), complemento([cloned, and, sequenced, the, gene, encoding, 'G4p2', and, have, shown, it, to, be, identical, to, 'MPT4', and, 'STO1'])]). relacion([sujeto(['STO1', was, isolated, as, a, multicopy, suppressor, of, 'TOM1,', an, uncharacterized, mutation, that]), verbo([leads]), complemento([to, 'temperature-sensitive', cell, cycle, arrest, at, the, 'G2/M', boundary])]). relacion([sujeto(['Suppression', of, these, mutations, by, 'G4p2', indicate, this, 'G4', nucleic, acid]), verbo([binding]), complemento([protein, may, function, in, signal, transduction, pathways, regulated, by, protein, 'kinases,', which, control, carbon, source, 'utilization,', and, in, cell, cycle, progression])]). relacion([sujeto(['Based', on, the, requirements, of, test, protocols, developed, to, evaluate, clinical, 'MRS', single, slice, and, volume, localisation, 'sequences,', two, clinical, test, 'objects,', 'STO1', and, 'STO2']), verbo([have]), complemento([been, developed])]). relacion([sujeto(['The', properties, of, a, range, of, potential, construction, materials]), verbo([have]), complemento([been, 'assessed,', demonstrating, that, the, 'water/Perspex', interface, produced, minimum, susceptibility, effects])]). relacion([sujeto(['The', design, of, the, objects]), verbo([has]), complemento([been, evaluated, in, trials, on, different, magnetic, resonance, 'instruments,', with, size, and, loading, being, adjusted, to, allow, use, on, currently, available, equipment])]). relacion([sujeto(['Appropriate', test, solutions, for, 31, 'P', and, 1, 'H', measurements]), verbo([have]), complemento([been, developed, and, their, properties, evaluated])]). relacion([sujeto(['Adenoviruses', recovered, from, the, northern, 'Stockholm', area, during, 1987, -, 1992]), verbo([have]), complemento([been, subjected, to, restriction, endonuclease, analysis])]). relacion([sujeto(['The', recessive, single]), verbo([nuclear]), complemento([gene, 'mutation,', named, 'gcr3,', caused, an, extremely, defective, growth, phenotype, on, fermentable, carbon, sources, such, as, 'glucose,', while, growth, on, respiratory, media, was, almost, normal])]). relacion([sujeto(['The', 'C-terminal', region, was, highly, 'charged,', and, an, acidic, stretch, was]), verbo([found]), complemento([in, it])]). relacion([sujeto(['The', flow, of, genetic, information, from, 'DNA', to, protein]), verbo([requires]), complemento(['polymerase-II-transcribed', 'RNA', characterized, by, the, presence, of, a, 5, '\'', -, cap])]). relacion([sujeto(['The', 'cap-binding', complex, '(', 'CBC),', consisting, of, the]), verbo([nuclear]), complemento(['cap-binding', protein, '(', 'NCBP)', 2, and, its, adaptor, 'NCBP1,', is, believed, to, bind, all, capped, 'RNA', and, to, be, necessary, for, its, processing, and, intracellular, localization])]). relacion([sujeto(['Here', we, show, that, 'NCBP1,', but, not, 'NCBP2,', is]), verbo([required]), complemento([for, cell, viability, and, 'poly(A)', 'RNA', export])]). relacion([sujeto(['NCBP3']), verbo([binds]), complemento(['mRNA,', associates, with, components, of, the, mRNA, processing, machinery, and, contributes, to, 'poly(A)', 'RNA', export])]). relacion([sujeto(['We', propose, the, existence, of, an, alternative, 'CBC']), verbo([involving]), complemento(['NCBP1', and, 'NCBP3', that, plays, a, key, role, in, mRNA, biogenesis])]). relacion([sujeto(['Both', vRNA, and, cRNA, are]), verbo([bound]), complemento([by, the, viral, 'RNA', polymerase, and, nucleoprotein, to, form, ribonucleoprotein, complexes])]). relacion([sujeto(['Viral', mRNAs, are, also, proposed, to, be]), verbo([bound]), complemento([by, the, 'RNA', polymerase, to, prevent, their, endonucleolytic, 'cleavage,', regulate, the, splicing, of, 'M1', 'mRNA,', and, facilitate, translation])]). relacion([sujeto(['We']), verbo([found]), complemento([that, viral, mRNA, associates, with, the, viral, 'non-structural', protein, 1, '(', 'NS1),', cellular, 'poly(A)-binding', protein, 1, '(', 'PABP1),', the, 20, kDa, subunit, 'NCBP1', of, the, nuclear, 'cap-binding', complex, '(', 'CBC),', the, 'RNA', and, export, 'factor-binding', protein, 'REF/Aly', and, the, translation, initiation, factor, eIF4E])]). relacion([sujeto(['However,', our, data]), verbo([suggest]), complemento([that, the, 'RNA', polymerase, might, not, form, part, of, the, viral, messenger, ribonucleoprotein, '(', 'mRNP)', complex])]). relacion([sujeto(['We', propose, a, model, in, which, viral, 'mRNAs,', by]), verbo([associating]), complemento([with, cellular, 'cap-binding', 'proteins,', follow, the, pathways, normally, used, by, cellular, mRNAs, for, 'splicing,', nuclear, export, and, translation])]). relacion([sujeto(['Treatment', of, cells, with, the, 'anti-cancer', drug, 5, -, fluorouracil, '(', 5, -, 'FU)']), verbo([causes]), complemento(['DNA', 'damage,', which, in, turn, affects, cell, proliferation, and, survival])]). relacion([sujeto(['Differential', expression, in, response, to, 5, -, 'FU', treatment, was, demonstrated, for, genes]), verbo([involved]), complemento([in, regulation, of, nucleotide, 'binding/metabolism', '(', 'ATAD2,', 'GNL2,', 'GNL3,', 'MATR3),', amino, acid, metabolism, '(', 'AHCY,', 'GSS,', 'IVD,', 'OAT),', cytoskeleton, organization, '(', 'KRT7,', 'KRT8,', 'KRT19,', 'MAST1),', transport, '(', 'MTCH1,', 'NCBP1,', 'SNAPAP,', 'VPS52),', and, oxygen, metabolism, '(', 'COX5A,', 'COX7C)'])]). relacion([sujeto(['Our', gene, expression, data]), verbo([suggest]), complemento([that, altered, regulation, of, nucleotide, 'metabolism,', amino, acid, 'metabolism,', cytoskeleton, 'organization,', 'transport,', and, oxygen, metabolism, may, underlie, the, differential, resistance, to, 5, -, 'FU', seen, in, these, cell, lines])]). relacion([sujeto(['Preconditioning', of, the, myocardium, rapidly]), verbo([induces]), complemento([a, number, of, transcription, 'factors,', which, are, likely, to, be, responsible, for, a, cascade, of, transcriptional, changes, underlying, the, development, of, delayed, adaptation])]). relacion([sujeto(['Identifying', these, changes]), verbo([provides]), complemento([insight, into, the, molecular, pathways, elicited, by, 'sub-lethal', ischaemia, and, the, mechanism, leading, to, delayed, adaptation])]). relacion([sujeto(['Three', novel, genes, and, six, genes, with, known, function, where, 'identified,', including, the, 'TGFbeta', receptor]), verbo([interacting]), complemento([protein, 1, ',', the, alpha, isoform, of, the, 'A', subunit, of, 'PP2', and, the, cap, binding, protein, 'NCBP1'])]). relacion([sujeto(['To', determine, whether, expression, of, these, genes, correlated, with, preconditioning, per, 'se,', expression, was, measured, in, myocardium, after, both, ischaemic, as, well, as, heat, shock]), verbo([induced]), complemento([preconditioning, following, 2, 'h,', 4, 'h,', and, 6, h, reperfusion])]). relacion([sujeto(['These', genes, were]), verbo([induced]), complemento([in, rabbit, myocardium, in, vivo, by, both, ischaemia, and, heat, 'shock,', consistent, with, a, fundamental, role, in, the, development, of, delayed, adaptation])]). relacion([sujeto(['The', well, described, role, of, 'PP2', in]), verbo([modulating]), complemento([the, 'mitogen-activated', protein, kinase, pathway, and, promoting, cell, survival, is, consistent, with, our, previous, 'work,', which, identified, the, reperfusion, injury, salvage, kinase, pathway, in, mediating, the, protective, effects, of, ischaemic, preconditioning])]). relacion([sujeto(['We']), verbo([report]), complemento([the, case, of, a, 40, -, 'year-old', woman, who, recovered, from, a, diffuse, metastatic, renal, cell, carcinoma, that, developed, from, a, kidney, allograft])]). relacion([sujeto(['Immunosuppression', was, 'discontinued,', and, transplant, nephrectomy, was, deliberately, delayed, based, on, the, expectation, that, the, tumor, mass, would]), verbo([trigger]), complemento([the, alloimmune, 'response,', which, was, stimulated, with, pegylated, 'interferon-α-2a'])]). relacion([sujeto(['Despite', this, severe, 'context,', the, present, case, shows, that, the, poor, prognosis, of, allograft, metastatic, renal, cell, carcinoma, could, be, dramatically, reversed, by, taking, advantage, of, the, donor, tumor, origin, to, actively]), verbo([induce]), complemento([a, specific, alloimmune, rejection, of, the, tumor])]). relacion([sujeto(['Neonatal', infection, can, sensitize, the, adult, substantia, nigra, '(', 'SN)', to, secondary, 'insults,']), verbo([causing]), complemento([a, decrease, in, antioxidant, capacity, which, may, lead, to, 'Parkinson\'s', disease, in, adults])]). relacion([sujeto([')', administration, of, lipopolysaccharide, '(', 'LPS)', on, interleukin, '(', 'IL)-1β,', the, antioxidant, regulator]), verbo([nuclear]), complemento(['factor-erythroid', 2, -, related, factor, 2, '(', 'Nrf2),', and, the, peroxisome, 'proliferator-activated', receptor, γ, coactivator, '(', 'PGC)-1α', in, rat, 'SN'])]). relacion([sujeto(['After', 65, 'days,', the, mRNA, level, of, 'IL-1β', was, significantly, 'increased,', in, parallel, with, a]), verbo([decrease]), complemento([in, that, of, the, 'rate-limiting', enzyme, in, glutathione, 'synthesis,', the, 'γ-glutamylcysteine', ligase, catalytic, subunit, '(', 'γGCLc),', 'Nrf2,', and, 'brain-derived', neurotrophic, factor, '(', 'BDNF)'])]). relacion([sujeto(['Protein', levels, of, γGCLc, and, 'Nrf2', were]), verbo([decreased]), complemento([while, 'IL-1β', protein, was, significantly, increased])]). relacion([sujeto(['These', 'LPS-induced', 'long-term', changes, correlated, with, a]), verbo([decrease]), complemento([in, phosphorylated, '(', 'active)', 'AKT', '(', 'pAKT)', and, phosphorylated, '(', 'inactive)', 'GSK-3β', '(', 'pGSK-3β)'])]). relacion([sujeto(['The', 'Spirulina-supplemented', diet]), verbo([decreased]), complemento(['IL-1β', protein, expression, in, 'SN', and, elevated, the, mRNA, level, of, 'γGCLc,', 'Nrf2', 'protein,', 'PGC-1α', 'protein,', and, pAKT])]). relacion([sujeto(['Thorium', is, natural, actinide, metal, with, potential, use, in]), verbo([nuclear]), complemento([energetics])]). relacion([sujeto(['The']), verbo([stimulated]), complemento([genes, were, involved, in, components, of, jasmonic, acid, and, salicylic, acid, signaling, pathways, and, various, abiotic, '(', e])]). relacion([sujeto(['Further,', 'up-regulation', of, phosphate, starvation, genes, and, 'down-regulation', of, genes]), verbo([involved]), complemento([in, phytic, acid, biosynthesis, indicated, that, thorium, disturbed, phosphate, uptake, or, signaling])]). relacion([sujeto(['Genes', potentially]), verbo([involved]), complemento([in, thorium, transport, could, be, 'zinc-induced', facilitator, 'ZIF2,', plant, cadmium, resistance, 'PCR2,', and, 'ABC', transporter, 'ABCG40'])]). relacion([sujeto(['This', study]), verbo([provides]), complemento([the, first, insight, at, the, processes, in, plants, exposed, to, thorium])]). relacion([sujeto(['Colorectal', cancer, constitutes, 33, '%', of, all, cancer, 'morbidity,', so, the, research, of, the, new, methods, for, colorectal, cancer, diagnosis, and, chemotherapy, monitoring, is]), verbo([gained]), complemento([its, momentum])]). relacion([sujeto(['Yet,', paraffin, may]), verbo([cause]), complemento([background, noise, in, spectroscopic, measurements, with, the, wavenumber, ranging, between, 900, 'cm(-1)', and, 3500, 'cm(-1)'])]). relacion([sujeto(['Unfortunately,', the, absence, of, tools, which, enable, monitoring, its, efficacy]), verbo([leads]), complemento([to, the, partial, response, or, 'non-response', frequently, seen, in, affected, patients])]). relacion([sujeto(['Hence,', diagnostic, instruments, are, also, being, sought, capable, of, monitoring, treatment, efficacy, so, as, to, enable, early, changes, of, chemotherapy, regimen, thus]), verbo([increasing]), complemento([the, chance, of, cure])]). relacion([sujeto(['Thus,', it, is, important, to]), verbo([find]), complemento([novel, 'non-invasive', treatment, strategies, among, various, therapeutic, 'HPV', vaccines])]). relacion([sujeto(['In', this, 'line,', the, full, length, of, 'high-mobility', group, box, 1, '(', 'HMGB1)', protein, as, well, as, an, 'HMGB1-derived', short, peptide, '(', 'Hp91)', was, used, as, an, adjuvant, for]), verbo([stimulating]), complemento([adaptive, immunity, and, developing, the, potency, of, these, vaccines])]). relacion([sujeto(['Our', data, showed, that, 'co-immunization', of, 'HPV16', 'E7', protein, with, 'Hp91', peptide, or, 'Hp91+Hp121', peptides, significantly]), verbo([increased]), complemento([the, secretion, of, 'IFN-γ,', 'IgG2a', antibody, 'response,', and, protected, 100, '%', of, mice, against, a, 'TC-1', tumor, challenge])]). relacion([sujeto(['Furthermore,', the, linkage, of, 'HMGB1', with, 'E7', antigen]), verbo([led]), complemento([to, enhance, the, immunogenicity, of, 'DNA', vaccine, especially, in, combination, with, 'Hp91', and, 'Hp121', peptides])]). relacion([sujeto(['These', findings]), verbo([suggest]), complemento([that, 'Hp91', 'peptide,', and, the, full, length, of, 'HMGB1', gene, could, be, an, efficient, adjuvant, for, improvement, of, therapeutic, 'HPV', 'protein-', and, 'DNA-based', 'vaccines,', respectively])]). relacion([sujeto(['The', obtained, results, revealed, that]), verbo([nuclear]), complemento([quadrupole, coupling, constant, '(', 'χ)', and, isotropic, chemical, shielding, '(', σiso, ')', values, of, nitrogen, nuclei, in, tetrazole, ring, of, five, possible, tautomeric, forms, of, 'tetrazole-5-thione,', i])]). relacion([sujeto(['Furthermore,', it, was, observed, that, by]), verbo([increasing]), complemento([participation, of, lone, pairs, of, nitrogen, atoms, in, the, ring, resonance, 'interactions,', the, σiso, values, around, them, were, 'increased;', while, their, χ, and, qzz, values, were, decreased])]). relacion([sujeto(['In', 'addition,', a, significant]), verbo([decrease]), complemento([was, noticed, in, χ, and, qzz, values, when, a, water, molecule, was, put, in, different, positions, near, the, tetrazole, ring, in, tautomers, 'A-E'])]). relacion([sujeto(['In', 'mono-hydrated', 'complexes,', the, σiso, values, around, nitrogen, atoms]), verbo([acting]), complemento([as, hydrogen, donors, in, hydrogen, bond, formation, '(', 'N-H…'])]). relacion([sujeto(['OH2', ')', were, 'decreased,', while, its, values, were]), verbo([increased]), complemento([for, nitrogen, atoms, acting, as, hydrogen, acceptors, in, hydrogen, bond, 'formation(N…'])]). relacion([sujeto(['Although', multiple, serum, antiretinal, autoantibodies, '(', 'ARAs)']), verbo([have]), complemento([been, reported, in, patients, with, paraneoplastic, and, 'non-paraneoplastic', autoimmune, retinopathy, '(', '(', 'n)pAIR),', not, all, retinal, antigens, involved, in, '(', 'n)pAIR', are, specified])]). relacion([sujeto(['We', identified, retinal, antigens, that]), verbo([have]), complemento([already, been, described, previously, '(', e])]). relacion([sujeto(['High', titers, of, autoantibodies, directed, against, 'photoreceptor-specific']), verbo([nuclear]), complemento([receptor, and, 'retinol-binding', protein, 3, were, more, common, in, patients, with, presumed, '(', 'n)pAIR', compared, to, uveitis, '(', p, =, 0.015, and, p, =, 0.018, ',', 'respectively)'])]). relacion([sujeto(['Lifestyle', and, pharmacological, interventions, in, unselected, obese, pregnant, women]), verbo([have]), complemento([been, unsuccessful, in, preventing, 'GDM'])]). relacion([sujeto(['Our', aim, was, to, develop, a, prediction, tool, for, early, identification, of, obese, women, at, high, risk, of, 'GDM', to, facilitate]), verbo([targeted]), complemento([interventions, in, those, most, likely, to, benefit])]). relacion([sujeto(['Twenty', one, candidate, biomarkers]), verbo([associated]), complemento([with, insulin, 'resistance,', and, a, targeted, nuclear, magnetic, resonance, '(', 'NMR)', metabolome, were, measured])]). relacion([sujeto(['A', model, based, on, clinical, and, anthropometric, variables, '(', 'age,', previous, 'GDM,', family, history, of, type, 2, 'diabetes,', systolic, blood, 'pressure,', sum, of, skinfold, 'thicknesses,', 'waist:height', and, 'neck:thigh', 'ratios)']), verbo([provided]), complemento([an, area, under, the, curve, of, 0.71, '(', 95, '%', 'CI', 0.68, -, 0.74, ')'])]). relacion([sujeto(['This']), verbo([increased]), complemento([to, 0.77, '(', 95, '%', 'CI', 0.73, -, 0.8, ')', with, addition, of, candidate, biomarkers, '(', random, 'glucose,', haemoglobin, 'A1c', '(', 'HbA1c),', 'fructosamine,', 'adiponectin,', sex, hormone, binding, 'globulin,', 'triglycerides),', but, was, not, improved, by, addition, of, 'NMR', metabolites, '(', 0.77, ;, 95, '%', 'CI', 0.74, -, 0.81, ')'])]). relacion([sujeto(['Tools', for, early, pregnancy, identification, of, obese, women, at, risk, of, 'GDM', are, described, which, could, enable]), verbo([targeted]), complemento([interventions, for, 'GDM', prevention, in, women, who, will, benefit, the, most])]). relacion([sujeto(['Allogeneic', transplantation, '(', 'Tx)', of]), verbo([induced]), complemento([pluripotent, stem, cells, '(', 'iPSCs)', is, a, promising, tissue, regeneration, therapy])]). relacion([sujeto(['However,', this, inevitably]), verbo([induces]), complemento(['macrophage-mediated', immune, response, against, the, 'graft,', limiting, its, therapeutic, efficacy])]). relacion([sujeto(['Monitoring', the, magnitude, of, the, immune, response, using, imaging, tools, would, be, useful, for, prolonging, graft, survival, and]), verbo([increasing]), complemento([the, therapy, longevity])]). relacion([sujeto(['Minimally', invasive, quantitative, detection, of]), verbo([activated]), complemento([macrophages, by, medical, imaging, technologies, such, as, positron, emission, tomography, '(', 'PET)', imaging, targets, translocator, protein, '(', 'TSPO),', which, is, highly, expressed, on, mitochondrial, 'membrane,', especially, in, activated, macrophage])]). relacion([sujeto(['BACKGROUND', 'Traumatic', brain, injury, '(', 'TBI)']), verbo([induces]), complemento([edema, on, the, uninjured, side, '(', i])]). relacion([sujeto(['MATERIAL', 'AND', 'METHODS', 'Mild', or, severe, 'TBI', was]), verbo([induced]), complemento([using, a, controlled, cortical, impact, model, in, 'rats,', immediately, followed, by, intraventricular, siRNA, infusions])]). relacion([sujeto(['RESULTS', 'Mild', or, severe, 'TBI']), verbo([induced]), complemento([different, patterns, of, 'CBT', edema])]). relacion([sujeto(['Furthermore,', following, mild, 'TBI,', brain, water, content, '(', 'BWC)', was]), verbo([increased]), complemento([at, 72, h, thereafter, and, 'AQP4', expression, was, increased, after, 168, 'h,', relative, to, 'non-injured', rats, '(', i])]). relacion([sujeto(['In', 'contrast,', following, severe, 'TBI,', 'BWC', was]), verbo([increased]), complemento([1, h, thereafter, and, 'AQP4', expression, was, transiently, enhanced, after, 1, 'h,', relative, to, sham])]). relacion([sujeto(['Three']), verbo([nuclear]), complemento([medicine, physicians, performed, the, diagnosis, and, rated, diagnostic, confidence, 'twice;', once, by, standard, visual, 'methods,', and, once, by, adding, of, 3, 'D-SSP'])]). relacion([sujeto(['Diagnostic', confidence, also]), verbo([increased]), complemento([in, 'DLB', '(', 'visual:', 3.2, ;, 3, 'D-SSP:', 4.1, ;, 'P', &, 'lt;', 0.001, ')', ',', followed, by, 'AD/MCI', '(', 'visual:', 3.1, ;, 3, 'D-SSP:', 3.8, ;, 'P', =, 0.002, ')', and, 'FTD', '(', 'visual:', 3.5, ;, 3, 'D-SSP:', 4.2, ;, 'P', =, 0.022, ')'])]). relacion([sujeto(['The', addition, of, 3, 'D-SSP', images, to, visual, analysis, helped, to, discriminate, different, types, of, dementia, in, 'FDG', 'PET', 'scans,', by, correcting, misdiagnoses, and]), verbo([enhancing]), complemento([diagnostic, confidence, in, the, correct, diagnosis])]). relacion([sujeto(['Improvement', of, diagnostic, accuracy, and, confidence, by, 3, 'D-SSP', images, might, help, to, determine, the]), verbo([cause]), complemento([of, dementia, and, appropriate, treatment])]). relacion([sujeto(['Here,', we, present, the, first]), verbo([report]), complemento([of, 'GS', in, the, pancreas, on, 'F-fluorodexyglucose', positron, emission, 'tomography/computed', tomography, '(', 'F-FDG', 'PET/CT)'])]). relacion([sujeto(['This', is, the, first]), verbo([report]), complemento([showing, the, 'F-FDG', 'PET/CT', findings, of, 'GS', in, the, pancreas])]). relacion([sujeto(['This', study]), verbo([suggested]), complemento([that, 'β-catenin', overexpression, in, the, nucleus, or, reduced, expression, in, the, 'membrane,', but, not, its, overexpression, in, 'cytoplasm,', could, serve, as, a, valuable, prognostic, predictor, for, 'CRC'])]). relacion([sujeto(['However,', additional, large, and, 'well-designed', prospective, studies, are]), verbo([required]), complemento([to, verify, our, results])]). relacion([sujeto(['Growth', 'hormone-releasing', hormone, '(', 'GHRH)', and, 'GHRH', receptor, '(', 'GHRH-R)']), verbo([have]), complemento([been, found, to, be, present, in, a, variety, of, tumoral, tissues, and, cell, lines])]). relacion([sujeto(['By', survival, analyses, of, multiple, cohorts, of, 'GC', 'patients,', we, identified, that]), verbo([increased]), complemento(['GHRH-R', in, tumor, specimens, correlates, with, poor, survival, and, is, an, independent, predictor, of, patient, prognosis])]). relacion([sujeto(['We', next, showed, that, 'MIA-602,', a, highly, potent, 'GHRH-R', 'antagonist,', effectively]), verbo([inhibited]), complemento(['GC', growth, in, cultured, cells])]). relacion([sujeto(['Mechanistically,', 'GHRH-R', antagonists]), verbo([target]), complemento(['GHRH-R', and, 'down-regulate', the, 'p21-activated', kinase, 1, '(', 'PAK1)-mediated', signal, transducer, and, activator, of, transcription, 3, '(', 'STAT3)/nuclear', 'factor-κB', '(', 'NF-κB)', inflammatory, pathway])]). relacion([sujeto(['Overall,', our, studies, establish, 'GHRH-R', as, a, potential, molecular]), verbo([target]), complemento([in, human, 'GC', and, suggest, treatment, with, 'GHRH-R', antagonist, as, a, promising, therapeutic, intervention, for, this, cancer])]). relacion([sujeto(['This', behavior, is, universal, across, all, energy, scales, from]), verbo([nuclear]), complemento([physics, to, chemistry, and, solid, state, systems])]). relacion([sujeto(['Although', typically, only, a, small, fraction, of, a, particle, wavefunction, extends, into, the, tunneling, 'region,', we, present, here, an, extreme, quantum, 'system:', a, gigantic, molecule, consisting, of, two, helium, 'atoms,', with, an, 80, '%', probability, that, its, two, nuclei, will, be]), verbo([found]), complemento([in, this, classical, forbidden, region])]). relacion([sujeto(['Imaging', a, tunneling, particle, shows, one, of, the, few, features, of, our, world, that, is, truly, 'universal:', the, probability, to]), verbo([find]), complemento([one, of, the, constituents, of, bound, matter, far, away, is, never, zero, but, decreases, exponentially])]). relacion([sujeto(['The', results, were, obtained, by, 'Coulomb', explosion, imaging, using, a, free, electron, laser, and, furthermore, yielded, 'He2\'s']), verbo([binding]), complemento([energy, of, '[', 'Formula:', see, 'text]', 'neV,', which, is, in, agreement, with, most, recent, calculations])]). relacion([sujeto(['The', evolutionary]), verbo([causes]), complemento([underlying, sex, chromosome, turnover, are, poorly, 'understood,', however])]). relacion([sujeto(['Here', we]), verbo([provide]), complemento([evidence, indicating, that, 'Wolbachia', bacterial, endosymbionts, triggered, the, evolution, of, new, sex, chromosomes, in, the, common, pillbug, 'Armadillidium', vulgare, 'We', identified, a, 3, -, 'Mb', insert, of, a, feminizing, 'Wolbachia', genome, that, was, recently, transferred, into, the, pillbug, nuclear, genome])]). relacion([sujeto(['Our', results, support, the, conclusion, that, the, 'Wolbachia', insert, is, now]), verbo([acting]), complemento([as, a, female, 'sex-determining', region, in, 'pillbugs,', and, that, the, chromosome, carrying, the, insert, is, a, new, 'W', sex, chromosome])]). relacion([sujeto(['Nuclear', lamins, are, the, major, components, of, the]), verbo([nuclear]), complemento([lamina, at, the, periphery, of, the, 'nucleus,', supporting, the, nuclear, envelope, and, participating, in, many, nuclear, 'processes,', including, 'DNA', 'replication,', transcription, and, chromatin, organization])]). relacion([sujeto(['A', group, of, 'diseases,', the, 'laminopathies,', is]), verbo([associated]), complemento([with, mutations, in, lamin, genes])]). relacion([sujeto(['Due', to, the, abnormal, presence, of, a, permanent, 'C-terminal', farnesyl, 'tail,', progerin, gradually, accumulates, on, the]), verbo([nuclear]), complemento(['membrane,', perturbing, a, diversity, of, signalings, and, transcriptional, events])]). relacion([sujeto(['The', accumulation, of, progerin]), verbo([has]), complemento([led, to, the, speculation, that, progerin, possesses, higher, stability, than, the, wild, type, lamin, 'A', protein])]). relacion([sujeto(['Members', of, the, 'Nuclear', 'Factor', 'Y', '(', 'NF-Y)', gene, 'family,', which]), verbo([have]), complemento([undergone, significant, expansion, and, functional, diversification, during, plant, 'evolution,', are, essential, for, this, symbiotic, liaison])]). relacion([sujeto(['Acting', in, a, partially, redundant, 'manner,', 'NF-Ys', were, shown, previously, to]), verbo([regulate]), complemento([bacterial, 'infection,', including, selection, of, a, superior, rhizobial, 'strain,', and, to, mediate, nodule, structure, formation])]). relacion([sujeto(['However,', the, exact, 'mechanism(s)', by, which, these, transcriptional, factors, exert, their, symbiotic, functions]), verbo([has]), complemento([remained, elusive])]). relacion([sujeto(['Three', affiliates, of, the, 'SHORT', 'INTERNODES/STYLISH', '(', 'SHI/STY)', transcription, factor, gene, 'family,', called, 'STY1,', 'STY2', and, 'STY3,', are, demonstrated, to, be, among, likely, direct]), verbo([targets]), complemento([of, 'LjNF-YA1', and, our, results, point, to, their, involvement, in, nodule, formation])]). relacion([sujeto(['The', 'VMAT-MCO', algorithm, implemented, in, 'RayStation', is, newly, developed, and]), verbo([requires]), complemento([an, 'integrated,', comprehensive, analysis, of, plan, 'generation,', 'delivery,', and, treatment, efficiency])]). relacion([sujeto(['The', plan, quality, was, compared, using, homogeneity, index, '(', 'HI)', and, conformity, index, '(', 'CI)', of, the, planning]), verbo([target]), complemento([volume, '(', 'PTV)', and, dose, sparing, of, organs, at, risk, '(', 'OARs)'])]). relacion([sujeto(['Given', the, diversity, of, the, tumor, 'location,', the, 10, plans, did, not]), verbo([have]), complemento([a, common, 'OAR', except, for, skin])]). relacion([sujeto(['No', statistically, significant, differences, were]), verbo([found]), complemento([between, 'VMAT-', and, 'IMRT-MCO', for, 'HI', and, 'CI', of, the, 'PTV', or, 'D50', and, 'Dmean', to, the, skin])]). relacion([sujeto(['The', moderate, energy, of, 'β-emitting', 177, 'Lu', '(', 'T½', =, 6.7, 'd,', 'Eβmax', =, 497, 'keV)']), verbo([has]), complemento([been, considered, as, a, potential, radionuclide, for, development, of, the, 'bone-seeking', radiopharmaceutical])]). relacion([sujeto(['Since', the, specific, activity, of, the, radiolabeled, carrier, molecules, should, be, 'high,', the, &, 'quot;no-carrier-added', 'radionuclides"']), verbo([have]), complemento(['sig-nificant', roles, in, nuclear, medicine])]). relacion([sujeto(['Many', researchers, illustrated, 'no-carrier-added', 177, 'Lu', 'production;', among, these, separation, techniques, such, as, ion, exchange, 'chromatography,', reversed, phase, 'ion-pair,', and, electrochemical, 'method,', extraction, chromatography]), verbo([has]), complemento([been, considered, more, capable, than, other, methods])]). relacion([sujeto(['The', 'NCA', 177, 'Lu', was, produced, with, specific, 'activ-ity', of, 48, 'Ci/mg', and, with, a, radinuclidic, purity, of, 99.99, '%', through, irradiation, of, enriched, 176, 'Yb']), verbo([target]), complemento(['(', 1, 'mg)', in, a, thermal, neutron, flux, of, 4, ×, 1013, n])]). relacion([sujeto(['Cap-binding', proteins, specifically]), verbo([bind]), complemento([to, the, 7, -, methyl, guanosine, '(', 'm7G)', functional, group, at, the, 5, '\'', end, of, eukaryotic, mRNAs])]). relacion([sujeto(['A', novel, 'Arabidopsis', thaliana, protein]), verbo([has]), complemento([been, identified, that, has, sequence, similarity, to, 'cap-binding', proteins, but, is, clearly, a, different, form, of, the, protein])]). relacion([sujeto(['The', most, obvious, primary, sequence, difference, is, the, substitution, of, two, of, the, eight]), verbo([conserved]), complemento([tryptophan, residues, with, other, aromatic, amino, acids, in, the, novel, protein])]). relacion([sujeto(['Measurements', of, the, dissociation, constant, for, this, protein, indicate, that, it]), verbo([binds]), complemento([m7GTP, 5, -, 20, -, fold, tighter, than, eukaryotic, initiation, factor, '(', 'eIF)(iso)4E'])]). relacion([sujeto(['Biochemical', analysis, and, yeast, 'two-hybrid', data, indicate, that, it]), verbo([interacts]), complemento([with, 'eIF(iso)4G', to, form, a, complex])]). relacion([sujeto(['Allele', mining, on, susceptibility, factors, offers, opportunities, to]), verbo([find]), complemento([new, sources, of, resistance, among, crop, wild, relatives, for, breeding, purposes])]). relacion([sujeto([pimpinellifolium, 'LA0411', 'accession,', which, encodes, a, potential, new, resistance, 'allele,', mainly, due, to, a, polymorphism]), verbo([associated]), complemento([with, an, amino, acid, change, within, eIF4E1, region, 'II'])]). relacion([sujeto(['We', confirmed, that, this, new, 'allele,', 'pot12,', is, indeed]), verbo([associated]), complemento([with, resistance, to, potato, virus, 'Y,', although, with, a, restricted, resistance, spectrum, and, a, very, low, durability, potential])]). relacion([sujeto(['This']), verbo([suggests]), complemento([that, mutations, occurring, in, eIF4E, region, 'II', only, may, not, be, sufficient, to, provide, efficient, and, durable, resistance, in, plants])]). relacion([sujeto(['Moreover,', this, approach, could, be, extended, to, seek, for, putative, new, resistance, alleles, by, screening, for, variant, forms, of, susceptibility, genes, encoding, plant, host, proteins, known, to]), verbo([interact]), complemento([with, viral, proteins])]). relacion([sujeto(['Plants', from, 'Brassicaceae', family, additionally]), verbo([conserve]), complemento([a, close, paralog, of, eIF4E, which, in, 'Arabidopsis', thaliana, has, two, copies, named, eIF4E1b, and, eIF4E1c])]). relacion([sujeto(['In', order, to, assess, the, efficiency, of, plant, 'non-canonical', '(', 'eIF4E1b/1c', and, 'nCBP)', and, canonical, '(', eIF4E, and, 'eIF(iso)4E)', eIF4E, proteins, to]), verbo([bind]), complemento([mRNAs, we, utilized, fluorescence, titrations, to, determine, accurate, binding, affinities, of, five, 'A'])]). relacion([sujeto(['We']), verbo([found]), complemento([that, eIF4E, binds, cap, analogs, from, 4, -, fold, to, 10, -, fold, stronger, than, 'eIF(iso)4E,', while, binding, affinities, of, nCBP, and, 'eIF(iso)4E', are, comparable])]). relacion([sujeto(['Furthermore,', eIF4E1c]), verbo([interacts]), complemento([similarly, strongly, with, the, cap, as, 'eIF4E,', but, eIF4E1b, binds, cap, analogs, ca])]). relacion([sujeto(['The', use, of, differentially, chemically, modified, cap, analogs, in]), verbo([binding]), complemento([studies, and, a, detailed, analysis, of, the, obtained, homology, models, gave, us, insight, into, the, molecular, characteristic, of, varying, 'cap-binding', abilities, of, 'Arabidopsis', eIF4E, isoforms])]). relacion([sujeto(['Vascular', calcification, significantly]), verbo([increases]), complemento([the, rates, of, cardiovascular, mortality, in, hemodialysis, '(', 'HD)', patients])]). relacion([sujeto(['Based', on, available, 'data,', 'NCBPs']), verbo([have]), complemento([equally, effective, with, 'CBPs', for, serum, phosphate, control])]). relacion([sujeto(['To', determine, if, bisphosphonates, are]), verbo([associated]), complemento([with, reduced, risk, of, acute, myocardial, infarction, '(', 'AMI)'])]). relacion([sujeto(['After', controlling, for, atherosclerotic, cardiovascular, disease, risk, factors, and, 'medications,', bisphosphonate, use, was]), verbo([associated]), complemento([with, an, increased, risk, of, incident, 'AMI', '(', hazard, 'ratio,', 1.38, ;, 95, '%', 'CI,', 1.08, -, 1.77, ;, 'P='])]). relacion([sujeto(['Our', observations, in, this, study, conflict, with, our, hypothesis, that, bisphosphonates]), verbo([have]), complemento([antiatherogenic, effects])]). relacion([sujeto(['They']), verbo([regulate]), complemento([target, mRNAs, by, promoting, degradation, or, by, influencing, translation, through, interaction, with, the, translation, initiation, machinery])]). relacion([sujeto(['Here', we, show, that, 'Caenorhabditis', elegans, 'PUF-8', functions, redundantly, with, the]), verbo([nuclear]), complemento([protein, 'TCER-1', in, the, 'post-transcriptional', maintenance, of, at, least, six, germline, mRNAs])]). relacion([sujeto(['The', levels, of, spliced, mRNAs, in, the, 'puf-8(-)', 'tcer-1(-)', double, mutant, are, only, 10, -, 30, '%', of, the, wild, 'type,', whereas, the, unspliced, forms]), verbo([increase]), complemento([by, '∼2-', to, 3, -, fold, compared, with, the, wild, type])]). relacion([sujeto(['These', two, proteins, colocalise, at, the, inner]), verbo([nuclear]), complemento(['periphery,', and, their, absence, leads, to, reduced, germ, cell, proliferation, and, to, sterility])]). relacion([sujeto(['A', yeast, 'two-hybrid', screen, of, 31, components, of, the]), verbo([nuclear]), complemento([pore, complex, and, mRNA, processing, machineries, identified, seven, proteins, involved, in, mRNA, export, as, potential, partners, of, 'PUF-8'])]). relacion([sujeto(['One', of, 'these,', the]), verbo([nuclear]), complemento(['cap-binding', protein, 'NCBP-2,', colocalises, with, 'PUF-8', in, the, nucleus])]). relacion([sujeto(['These', results]), verbo([reveal]), complemento([two, important, unexpected, aspects, of, 'PUF', 'proteins:', 'that,', in, addition, to, the, 'C-terminal', 'PUF', 'domain,', the, 'N-terminal', domain, is, crucial, for, 'PUF', 'function,', and, that, 'PUF', proteins, have, a, novel, role, in, mRNA, maintenance])]). relacion([sujeto(['We', propose, that, 'PUF', 'proteins,', in, addition, to, their, known, cytoplasmic, 'roles,']), verbo([participate]), complemento([in, nuclear, processing, 'and/or', export, of, mRNAs])]). relacion([sujeto(['Nitrogen-containing', bisphosphonates, '(', 'NCBPs)']), verbo([have]), complemento([been, widely, used, as, standard, supportive, therapy, to, reduce, 'skeletal-related', events, '(', 'SREs)', in, myeloma, patients, through, suppression, of, osteoclast, activity])]). relacion([sujeto(['In', various, prospective, randomized, trials, that, were, performed, following, preliminary]), verbo([reports]), complemento([concerning, 'efficacy,', 'NCBPs', have, shown, a, significant, beneficial, effect, on, myeloma, bone, disease, through, both, suppression, of, bone, resorption, and, direct, antimyeloma, activity])]). relacion([sujeto(['Thus,', 'NCBPs']), verbo([have]), complemento([an, influence, on, many, types, of, human, cells])]). relacion([sujeto(['Such', apoptosis, of, monocytic, cells, was]), verbo([suppressed]), complemento([by, the, addition, of, farnesol, or, geranylgeraniol])]). relacion([sujeto(['These', findings]), verbo([suggest]), complemento([that, the, inhibition, of, 'monocyte-lineage', cells, or, 'DCs', by, 'NCBPs', might, interfere, with, phagocytic, activity, or, 'pathogen-presenting', activity])]). relacion([sujeto(['Unfortunately,', 'HBP']), verbo([has]), complemento(['limitations,', including, questionable, device, validity, and, patient, compliance])]). relacion([sujeto(['Thus,', it, is, important, to, identify, feasible, alternative, techniques, to, measure, 'BP', in, the, office, that, will]), verbo([increase]), complemento([the, accuracy, of, the, diagnosis])]). relacion([sujeto(['Preservation', of, blood, flow, and, both, celiac, and, pyloric, branches, of, the, vagal, nerve, may]), verbo([decrease]), complemento([the, incidence, of, the, stasis])]). relacion([sujeto(['A', large, randomized, control, trial, investigating, both, 'short-', and, 'long-term', outcomes, after, 'PPG', is]), verbo([required]), complemento([to, elucidate, the, primary, cause, of, postoperative, stasis])]). relacion([sujeto([the, aim, of, this, study, was, to, determine, whether, 'nitrogen-containing', bisphosphonate, '(', 'NCBP)', therapy, is]), verbo([associated]), complemento([with, the, prevalence, of, cardiovascular, calcification])]). relacion([sujeto(['Experimental', data]), verbo([suggest]), complemento([that, 'NCBP', might, limit, cardiovascular, 'calcification,', which, has, implications, for, disease, prevention])]). relacion([sujeto(['After', adjusting, for, 'age;', body, mass, 'index;', demographic, 'data;', 'diabetes;', 'smoking;', blood, 'pressure;', cholesterol, 'levels;', and, 'statin,', hormone, 'replacement,', and, 'renin-angiotensin', inhibitor, 'therapy,', 'NCBP', use, was]), verbo([associated]), complemento([with, a, lower, prevalence, of, cardiovascular, calcification, in, women, '≥', 65, years, of, age, '(', prevalence, 'ratio:', 'AVC', 0.68, '[', 95, '%', confidence, interval, '(', 'CI):', 0.41, to, 1.13, ']', ;, 'AVRC', 0.65, '[', 95, '%', 'CI:', 0.51, to, 0.84, ']', ;, 'MAC', 0.54, '[', 95, '%', 'CI:', 0.33, to, 0.93, ']', ;, 'TAC', 0.69, '[', 95, '%', 'CI:', 0.54, to, 0.88, ']', ;, 'CAC', 0.89, '[', 95, '%', 'CI:', 0.78, to, 1.02, ']', ')', ',', whereas, calcification, was, more, prevalent, in, 'NCBP', users, among, the, 2, ',', 181, women, &, 'lt;65', years, of, age, '(', 'AVC', 4.0, '[', 95, '%', 'CI:', 2.33, to, 6.89, ']', ;, 'AVRC', 1.92, '[', 95, '%', 'CI:', 1.42, to, 2.61, ']', ;, 'MAC', 2.35, '[', 95, '%', 'CI:', 1.12, to, 4.84, ']', ;, 'TAC', 2.17, '[', 95, '%', 'CI:', 1.49, to, 3.15, ']', ;, 'CAC', 1.23, '[', 95, '%', 'CI:', 0.97, to, 1.57, ']', ')'])]). relacion([sujeto([among, women, in, the, diverse, 'MESA', 'cohort,', 'NCBPs', were]), verbo([associated]), complemento([with, decreased, prevalence, of, cardiovascular, calcification, in, older, subjects, but, more, prevalent, cardiovascular, calcification, in, younger, ones])]). relacion([sujeto([312, 'Asp/Asn', +, 'Asn/Asn']), verbo([decreased]), complemento([a, 0.59, fold, '(', 'ORadj', =, 0.59, ',', 95, '%', 'CI', =, 0.35, -, 0.99, ',', chi2, =, 3.99, ',', 'P', &, 'lt;', 0.05, ')', ',', when, 'sex,', workage, and, intensity, of, benzene, exposure, were, adjusted])]). relacion([sujeto([312, 'Asp/Asn', +, 'Asn/Asn', more]), verbo([decreased]), complemento(['(', 'ORadj', =, 0.13, ',', 95, '%', 'CI', =, 0.04, -, 0.51, ',', chi2, =, 8.93, ',', 'P', &, 'lt;', 0.01, ')'])]). relacion([sujeto(['Accordingly,', mutations, in, the, gene, encoding, eIF4E]), verbo([have]), complemento([been, identified, as, a, source, of, recessive, resistance, in, several, plant, species])]). relacion([sujeto(['In', common, 'bean,', 'Phaseolus', 'vulgaris,', four, recessive, 'genes,', 'bc-1,', 'bc-2,', 'bc-3', and, 'bc-u,']), verbo([have]), complemento([been, proposed, to, control, resistance, to, the, potyviruses, 'Bean', common, mosaic, virus, '(', 'BCMV)', and, 'Bean', common, mosaic, necrosis, virus])]). relacion([sujeto(['Bean', genotypes]), verbo([reported]), complemento([to, carry, 'bc-3', resistance, were, found, specifically, to, carry, 'non-silent', mutations, at, codons, 53, ',', 65, ',', 76, and, 111, in, eIF4E])]). relacion([sujeto(['F(2)', plants, homozygous, for, the, eIF4E, mutant, allele, were]), verbo([found]), complemento([to, display, at, least, the, same, level, of, resistance, to, 'BCMV', as, the, parental, resistant, genotype])]). relacion([sujeto(['At', 6, weeks, after, 'inoculation,', all, 'F(2)', plants]), verbo([found]), complemento([to, be, 'BCMV', negative, by, 'enzyme-linked', immunosorbent, assay, were, found, to, be, homozygous, for, the, mutant, eIF4E, allele])]). relacion([sujeto(['In', 'F(3)', plants, homozygous, for, the, mutated, 'allele,', virus, resistance, was, subsequently]), verbo([found]), complemento([to, be, stably, maintained])]). relacion([sujeto(['In', 'conclusion,', allelic, eIF4E, appears, to, be]), verbo([associated]), complemento([with, a, major, component, of, potyvirus, resistance, present, in, 'bc-3', genotypes, of, bean])]). relacion([sujeto(['Here,', we, identify, a, role, of, the, 'Caenorhabditis', elegans]), verbo([nuclear]), complemento([export, receptor, 'XPO-1', and, the, 'cap-binding', proteins, 'CBP-20/NCBP-2', and, 'CBP-80/NCBP-1', in, this, process])]). relacion([sujeto(['The', 'RNA-mediated', interference, of, any, of, these, genes]), verbo([causes]), complemento([retarded, heterochronic, phenotypes, similar, to, those, observed, for, animals, with, mutations, in, the, 'let-7', miRNA, or, core, miRNA, machinery, genes])]). relacion([sujeto(['An', involvement, of, 'XPO-1', in, miRNA, biogenesis, is]), verbo([conserved]), complemento([in, 'Drosophila,', in, which, knockdown, of, 'Embargoed/XPO-1', or, its, chemical, inhibition, through, leptomycin, 'B', causes, 'pri-miRNA', accumulation])]). relacion([sujeto(['Our', findings, demonstrate, that, 'XPO-1/Emb']), verbo([promotes]), complemento([the, 'pri-miRNA-to-pre-miRNA', processing, and, we, propose, that, this, function, involves, intranuclear, transport, 'and/or', nuclear, export, of, primary, miRNAs])]). relacion([sujeto(['In', rat, experiments, the, ability, of, noncollagen, bone, proteins, '(', 'NCBP)', in, the, composition, of, osteoplactic, modified, material, 'Gapkol', '(', not, tanned, in, formalin, and, subjected, to, vacuum, 'extraction)', to]), verbo([increase]), complemento([bone, reparation, in, comparison, with, traditional, 'Gapkol', was, studied])]). relacion([sujeto(['It', was, shown, that, 'Gapkol', with, 'NCBP', '(', not, tanned, in, formalin, and, subjected, to, vacuum, 'extraction)']), verbo([increased]), complemento([reparative, osteogenesis])]). relacion([sujeto([watershed, adjacent, to, the, 'MRB,', was, selected, to, document, elemental, concentrations, in, fish, used, for, other, aspects, of, a, larger, study, and, to]), verbo([provide]), complemento([additional, contemporaneous, data, on, background, elemental, concentrations])]). relacion([sujeto(['The', whole, fish, were, composited, by, 'station,', 'species,', and, gender, for, analysis, of, arsenic, '(', 'As),']), verbo([lead]), complemento(['(', 'Pb),', and, selenium, '(', 'Se)', by, atomic, absorption, spectroscopy, and, for, cadmium, '(', 'Cd),', copper, '(', 'Cu),', and, zinc, '(', 'Zn)', by, 'inductively-coupled', plasma, emission, spectroscopy])]). relacion([sujeto([at, 'John', 'Martin', 'Reservoir,', 'CO),', where, concentrations]), verbo([have]), complemento([been, elevated, historically, and, increased, slightly, '(', to, 3.8, -, 4.7, microg, 'g-(1)', in, bass, and, 'carp);', and, 'Pb,', 'Cd,', and, 'Zn', at, 'Station', 67, '(', 'Allegheny', 'R'])]). relacion([sujeto([at, 'Natrona,', 'PA),', where, levels, of, these, metals, were, high, in, the, past, and]), verbo([increased]), complemento([from, 1986, to, 1995])]). relacion([sujeto(['Mirex', was, detected, at, only, two, 'sites,', both, in, 'Louisiana,', and, toxaphene, was]), verbo([found]), complemento([exclusively, in, the, lower, 'MRB'])]). relacion([sujeto(['Calmodulin-like', neuronal, 'Ca2+-binding', proteins, '(', 'NCBPs)', are]), verbo([expressed]), complemento([primarily, in, neurons, and, contain, a, combination, of, four, functional, and, nonfunctional, 'EF-hand', 'Ca2+-binding', motifs])]). relacion([sujeto(['Our', results, demonstrate, that, 'GCAP1,', 'GCAP2,', 'GC1', and, 'GC2', are]), verbo([expressed]), complemento([in, human, rod, and, cone, 'photoreceptors,', while, 'GCAP3', is, expressed, exclusively, in, cones])]). relacion([sujeto(['As', a, consequence, of, extensive, 'modification,', the, 'GCAP3', gene, is, not]), verbo([expressed]), complemento([in, mouse, retina])]). relacion([sujeto(['Furthermore,', sequence, comparisons, and, evolutionary, trace, analysis, coupled, with, functional, testing, of, the, different, 'GCAPs', allowed, us, to, identify, the, key]), verbo([conserved]), complemento([residues, that, are, critical, for, 'GCAP', structure, and, 'function,', and, to, define, 'class-specific', residues, for, the, 'NCBP', subfamilies])]). relacion([sujeto(['Therefore,', the, study, of, retinal, 'Ca(2+)-binding', 'proteins,', which, frequently]), verbo([mediate]), complemento(['Ca(2+)', 'signaling,', has, given, rise, to, the, important, discovery, of, two, subfamilies, of, these, 'proteins,', neuronal, 'Ca(2+)-binding', proteins, '(', 'NCBPs)', and, 'calcium-binding', proteins, '(', 'CaBPs),', that, display, similarities, to, calmodulin, '(', 'CaM)'])]). relacion([sujeto(['The', expansion, of, the, 'CaM-like', protein, family]), verbo([reveals]), complemento([diversification, among, 'Ca(2+)-binding', proteins, that, evolved, on, the, basis, of, the, classic, 'molecule,', 'CaM'])]). relacion([sujeto([elegans, '(', 'IFE-1,', 'IFE-2,', and, 'IFE-3)', was]), verbo([reported]), complemento([previously])]). relacion([sujeto(['The', present, study, describes, two, more, eIF4E, isoforms]), verbo([expressed]), complemento([in, 'C'])]). relacion([sujeto(['IFE-3,', the, most, closely, related, to, mammalian, 'eIF4E-1,']), verbo([binds]), complemento([only, 7, -, methylguanosine, caps, and, is, essential, for, viability])]). relacion([sujeto(['In', 'contrast,', three, closely, related, isoforms, '(', 'IFE-1,', 'IFE-2,', and, 'IFE-5)']), verbo([bind]), complemento([2, ',', 2, ',', 7, -, trimethylguanosine, caps, and, are, partially, 'redundant,', but, at, least, one, functional, isoform, is, required, for, viability])]). relacion([sujeto(['IFE-4,', which]), verbo([binds]), complemento([only, 7, -, methylguanosine, 'caps,', is, most, closely, related, to, an, unusual, eIF4E, isoform, found, in, plants, '(', 'nCBP)', and, mammals, '(', '4E-HP)', and, is, not, essential, for, viability, in, any, combination, of, 'IFE', knockout])]). relacion([sujeto(['Concentrations', of, toxaphene, also, 'declined,', as, did, its, 'incidence,', from, 88, '%', of, the, stations, sampled, in, 1980, -, 1981, to, 64, '%', in, 1986, ;, 'however,', analytical, problems, with, the, 1986, samples, may]), verbo([have]), complemento([contributed, to, the, latter])]). relacion([sujeto(['For', 'chlordane-related', 'residues,', mean, concentrations, were, lower, that]), verbo([reported]), complemento(['previously,', and, 'trans-nonachlor', continued, to, replace, 'cis-chlordane', as, the, most, abundant, component])]). relacion([sujeto(['Collectively,', these, findings]), verbo([suggested]), complemento([a, lower, rate, of, chlordane, influx, to, the, aquatic, 'environment;', 'however,', a, point, source, of, cyclodiene, insecticides, to, the, 'Mississippi', 'R'])]). relacion([sujeto(['Residues', of, 'mirex,', 'PCA,', 'BHC', 'isomers,', 'endrin,', 'heptachlor,', and, 'HCB', were, either]), verbo([found]), complemento([at, relatively, few, '(', &, 'lt;', 25, '%', ')', of, the, stations, sampled, in, 1986, or, were, characterized, by, relatively, low, concentrations])]). relacion([sujeto(['Concentrations', of, the, herbicide, 'Dacthal', '(', 'DCPA)', were, also, 'low,', but, incidence]), verbo([increased]), complemento([from, 46, '%', of, the, stations, sampled, in, 1984, to, 61, '%', in, 1986])]). relacion([sujeto(['In', 'general,', organochlorine, chemical, concentrations, were, lower, in, 1986, than, at, any, time]), verbo([reported]), complemento([previously])]). relacion([sujeto(['Mean', concentrations, of, 'Cu']), verbo([increased]), complemento([and, concentrations, of, 'As', decreased, relative, to, the, 1984, 'collection,', but, these, changes, may, reflect, subtle, differences, in, the, species, composition, of, the, 1986, collection, relative, to, other, 'collections;', concentrations, of, both, elements, differ, greatly, among, fishes])]). relacion([sujeto(['Moreover,', and, in, contrast, to, the, other, elements, measured, in, 1986, ',', concentrations, of, 'Hg', and, 'Se', were, high, enough, to, constitute, a, threat, to, pisc, 'It']), verbo([has]), complemento([been, shown, that, the, monomethylated, cap, structure, plays, important, roles, in, 'pre-mRNA', splicing, and, nuclear, export, of, 'RNA'])]). relacion([sujeto(['As', a, candidate, for, the, factor]), verbo([involved]), complemento([in, these, nuclear, events, we, have, previously, purified, an, 80, kDa, nuclear, cap, binding, protein, '(', 'NCBP)', from, a, 'HeLa', cell, nuclear, extract, and, isolated, its, 'full-length', cDNA])]). relacion([sujeto(['In', this, 'report,', in, order, to, obtain, a, clue, to, the, cellular, functions, of, 'NCBP,', we, attempted, to, identify, a, 'factor(s)', that]), verbo([interacts]), complemento([with, 'NCBP'])]). relacion([sujeto(['We', designated, the, proteins, encoded, by, these, clones, 'NIPs', '(', 'NCBP']), verbo([interacting]), complemento(['proteins)'])]). relacion([sujeto(['NIP1', and, 'NIP2']), verbo([have]), complemento([an, 'RNP', 'consensus-type', 'RNA', binding, 'domain,', whereas, 'NIP3', contains, a, unique, domain, of, 'Arg-Glu', or, 'Lys-Glu', dipeptide, repeats])]). relacion([sujeto(['We', also, show, that, 'NCBP']), verbo([requires]), complemento(['NIP1', for, binding, to, the, cap, structure])]). relacion([sujeto(['Possible', roles, of, 'NIPs', in, 'cap-dependent']), verbo([nuclear]), complemento([processes, are, discussed])]). relacion([sujeto(['It']), verbo([has]), complemento([been, shown, that, the, monomethylated, cap, structure, plays, important, roles, in, nuclear, events])]). relacion([sujeto(['The', cap, structure]), verbo([has]), complemento([been, implicated, in, the, enhancement, of, 'pre-mRNA', splicing])]). relacion([sujeto(['More', 'recently,', this, structure]), verbo([has]), complemento([also, been, suggested, to, facilitate, 'RNA', transport, from, the, nucleus, to, the, cytoplasm])]). relacion([sujeto(['We']), verbo([have]), complemento([previously, identified, and, purified, an, 80, kD, 'Nuclear', 'Cap', 'Binding', 'Protein', '(', 'NCBP)', from, a, 'HeLa', cell, nuclear, 'extract,', which, could, possibly, mediate, these, nuclear, activities])]). relacion([sujeto(['Transfection', experiments, demonstrated, that, the, 'epitope-tagged', 'NCBP,', transiently]), verbo([expressed]), complemento([in, 'HeLa', 'cells,', was, localized, exclusively, in, the, nucleoplasm])]). relacion([sujeto(['Similar', experiments, using, a, truncated, 'NCBP', cDNA, indicated, that, this]), verbo([nuclear]), complemento([localization, activity, is, conferred, by, the, 'N-terminal', 70, 'amino-acid', region])]). relacion([sujeto(['Mean', concentrations, of, dieldrin]), verbo([have]), complemento([not, changed, since, 1978, -, 79, ;, concentrations, remained, highest, in, 'Hawaii', and, in, the, 'Great', 'Lakes'])]). relacion([sujeto(['Mean', chordane, concentrations, did, not, change, from, 1980, -, 81, to, 1984, ',', following, a, period, of, 'decline;', 'however,trans-nonachlor', 'replacedcis-chlordane', as, the, most, abundant, 'component,']), verbo([suggesting]), complemento([a, lower, influx, of, chlordane, to, the, aquatic, environment])]). relacion([sujeto(['Residues', of, other, 'organochlorines-mirex,', pentachloroanisole, '(', 'PCA),', benzene, hexachloride, '(', 'BHC)', 'isomers,', 'endrin,', 'heptachlor,', hexachlorobenzene, '(', 'HCB),', and, 'Dacthal(®)', '(', 'DCPA)-were', either]), verbo([found]), complemento([at, relatively, few, '(', &, 'lt;25%)', of, the, stations, sampled, in, 1984, or, were, characterized, by, relatively, low, concentrations])]). relacion([sujeto(['In', 'general,', organochlorine, concentrations, were, lower, in, 1984, than, at, any, time]), verbo([reported]), complemento([previously])]). relacion([sujeto(['The', mean, concentrations, of, selenium, and]), verbo([lead]), complemento([were, significantly, lower, than, in, the, previous, 'NCBP', collection, '(', 1980, -, 81, ')'])]). relacion([sujeto(['Of', greatest, 'significance,']), verbo([lead]), complemento([concentrations, declined, steadily, from, 1976, to, 1984, ',', suggesting, that, regulatory, measures, have, successfully, reduced, the, influx, of, lead, to, the, aquatic, environment])]). relacion([sujeto(['Human', neutrophil, cobalamin]), verbo([binding]), complemento([protein, '(', 'NCBP)', is, located, exclusively, in, the, neutrophil, secondary, granules])]). relacion([sujeto(['The', soluble, stimuli, 'formlymethionyl-leucyl-phenylalanine', and, the, 'low-molecular-weight', complement, fragment, 'C5a', both]), verbo([promote]), complemento([the, 'dose-dependent', release, of, 'NCBP', from, cytochalasin, 'B-treated', neutrophils, in, vitro])]). relacion([sujeto(['The', extracellular, discharge, of, 'NCBP']), verbo([induced]), complemento([by, higher, secretagogue, is, inhibited, by, prior, exposure, of, neutrophils, to, the, corticosteroids, hydrocortisone, and, methylprednisolone, and, the, nonsteroidal, antiinflammatory, agents, indomethacin, and, ibuprofen])]). relacion([sujeto(['These', findings, support, the, hypothesis, that, antiinflammatory, agents]), verbo([prevent]), complemento([neutrophil, activation, in, vitro, by, inhibition, of, 'stimulus-receptor', coupling])]). relacion([sujeto(['The', ability, of, noncollagenous, bone, proteins, '(', 'NCBP)', to]), verbo([inhibit]), complemento([calcium, phosphate, precipitation, in, vitro, raises, the, question, as, to, the, nature, and, the, relative, efficiency, of, such, proteins, in, vivo])]). relacion([sujeto(['Their', relative, activity, was, measured, by, their, efficiency, in]), verbo([preventing]), complemento([hydroxyapatite, growth])]). relacion([sujeto(['On', a, weight, '(', of, protein, 'recovered)', 'basis,', the, activity, is, about, equally, divided, between, the, 'Gla-containing', 'protein,', 'osteocalcin,', and, a]), verbo([phosphorylated]), complemento([protein, essentially, the, same, as, osteonectin])]). relacion([sujeto(['On', a, molecular, weight, 'basis,', the, activity, of, the]), verbo([phosphorylated]), complemento([protein, is, almost, three, times, higher, than, that, of, the, 'Gla-containing', protein])]). relacion([sujeto(['Finally,', the, inhibitory, activity, of, the]), verbo([phosphorylated]), complemento([protein, is, alkaline, phosphatase, sensitive])]). relacion([sujeto(['The', properties, of, this, protein, could]), verbo([provide]), complemento([a, means, of, regulating, the, solubility, of, bone, mineral, and, maintaining, an, equilibrium, of, calcium, between, bone, and, blood])]). relacion([sujeto(['The']), verbo([nuclear]), complemento(['cap-binding', complex, '(', 'CBC)', is, a, heterodimer, composed, of, 'CBP20', and, 'CBP80', subunits, and, has, roles, in, the, biogenesis, of, messenger, 'RNAs', '(', 'mRNAs),', small, nuclear, 'RNAs', '(', 'snRNAs)', and, microRNAs])]). relacion([sujeto(['CBP20', is, a, phylogenetically]), verbo([conserved]), complemento([protein, that, interacts, with, the, 7, -, methyl, guanosine, '(', 'm7G)', cap, added, to, the, 5, '\'', end, of, all, 'RNA', polymerase, 'II', transcripts])]). relacion([sujeto(['CBP80']), verbo([ensures]), complemento([high, affinity, binding, of, the, cap, by, 'CBP20', and, provides, a, platform, for, interactions, with, other, factors])]). relacion([sujeto(['The', 'CBP20S', transcript]), verbo([has]), complemento([an, 'in-frame', 'deletion,', leading, to, the, translation, of, a, protein, lacking, most, of, the, 'RNA', recognition, motif, '(', 'RRM)'])]). relacion([sujeto(['We', show, that, 'CBP20S', is]), verbo([conserved]), complemento([among, mammalian, species, and, is, expressed, in, human, cell, lines, and, bone, marrow, cells])]). relacion([sujeto(['Unlike', the, 'full-length', 'CBP20,', 'CBP20S', does, not]), verbo([bind]), complemento(['CBP80', or, the, m7G, cap])]). relacion([sujeto(['Nevertheless,', 'CBP20S', does]), verbo([bind]), complemento(['mRNA,', is, localized, to, an, active, transcription, site, and, redistributed, to, nucleolar, caps, upon, transcription, inhibition])]). relacion([sujeto(['Our', results]), verbo([suggest]), complemento([that, this, novel, form, 'CBP20S', plays, a, role, in, transcription, 'and/or', 'RNA', processing, independent, of, 'CBP80', or, the, cap])]). relacion([sujeto(['The', 'CBP80/ABH1', protein, is, part, of, the, 'Cap', 'Binding', 'Complex', '(', 'CBC),', which, is]), verbo([involved]), complemento([in, plant, responses, to, drought, stress, conditions])]). relacion([sujeto(['Transformed', plants, with, a]), verbo([decreased]), complemento([level, of, 'CBP80/ABH1', display, increased, tolerance, to, water, shortage, conditions])]). relacion([sujeto(['The', export, of, messenger, 'RNAs', '(', 'mRNAs)', is, the, final, of, several]), verbo([nuclear]), complemento([posttranscriptional, steps, of, gene, expression])]). relacion([sujeto(['The', formation, of, 'export-competent', mRNPs]), verbo([involves]), complemento([the, recruitment, of, export, factors, that, are, assumed, to, facilitate, transport, of, the, mature, mRNAs])]). relacion([sujeto(['Using', in, vitro, splicing, 'assays,', we, show, that, a, core, set, of, export, 'factors,', including, 'ALYREF,', 'UAP56', and, 'DDX39,', readily]), verbo([associate]), complemento([with, the, spliced, 'RNAs', in, an, 'EJC', '(', exon, junction, 'complex)-', and, 'cap-dependent', manner])]). relacion([sujeto(['In', order, to, elucidate, how, 'ALYREF', and, other, export, adaptors]), verbo([mediate]), complemento([mRNA, 'export,', we, conducted, a, computational, analysis, and, discovered, four, 'short,', 'conserved,', linear, motifs, present, in, 'RNA-binding', proteins])]). relacion([sujeto(['We', show, that, mutation, in, one, of, the, new, motifs, '(', 'WxHD)', in, an, unstructured, region, of, 'ALYREF', reduced, 'RNA']), verbo([binding]), complemento([and, abolished, the, interaction, with, eIF4A3, and, 'CBP80'])]). relacion([sujeto(['Additionally,', the, mutation, impaired, proper, localization, to]), verbo([nuclear]), complemento([speckles, and, export, of, a, spliced, reporter, mRNA])]). relacion([sujeto(['Our', results]), verbo([reveal]), complemento([important, details, of, the, orchestrated, recruitment, of, export, factors, during, the, formation, of, export, competent, mRNPs])]). relacion([sujeto(['The', genetic, basis, of, hearing]), verbo([loss]), complemento([in, humans, is, relatively, poorly, understood])]). relacion([sujeto(['In', recent, 'years,', experimental, approaches, including, laboratory, studies, of, early, onset, hearing]), verbo([loss]), complemento([in, inbred, mouse, 'strains,', or, proteomic, analyses, of, hair, cells, or, hair, 'bundles,', have, suggested, new, candidate, molecules, involved, in, hearing, function])]). relacion([sujeto(['Genes']), verbo([found]), complemento([to, contain, 'SNPs', with, low, 'p-values', were, then, investigated, in, 3417, adults, in, the, 'G-EAR', study, of, hearing])]). relacion([sujeto(['For', low, 'frequencies,', rs9567638, in, 'LCP1', also]), verbo([enhanced]), complemento([hearing, in, females, '(', p, =, 0.0011, ',', β, =, -, 1.76, 'dB;', males, p, =, 0.23, ',', β, =, 0.61, 'dB,', 'likelihood-ratio', test, p, =, 0.006, ')'])]). relacion([sujeto(['Although', the, 'ALSPAC', results, were, not, 'replicated,', a, 'SNP', in, 'LCP1,', 'rs17601960,', is, in, strong, 'LD', with, 'rs9967638,', and, was]), verbo([associated]), complemento([with, enhanced, low, frequency, hearing, in, adult, females, in, 'G-EAR', '(', p, =, 0.00084, ')'])]). relacion([sujeto(['There', was, evidence, to]), verbo([suggest]), complemento([that, multiple, 'SNPs', in, 'CTIF', may, contribute, a, small, detrimental, effect, to, 'hearing,', and, that, a, 'sex-specific', locus, in, 'LCP1', is, protective, of, hearing])]). relacion([sujeto(['This', is, the, first]), verbo([report]), complemento([of, a, possible, association, between, 'LCP1', and, hearing, function])]). relacion([sujeto(['Osteosarcoma', '(', 'OS)', is, 'a malignant', bone, tumor, very, often, with, pulmonary, metastasis, and, is, the, main]), verbo([cause]), complemento([of, 'OS', mortality])]). relacion([sujeto(['Differentially']), verbo([expressed]), complemento([genes, '(', 'DEGs)', between, two, groups, were, identified, by, limma, packages, in, 'R and', classical, 't-test', with, the, threshold, of, the, false, discovery, rate, '(', 'FDR)', &, 'lt;0'])]). relacion([sujeto(['BAI2,', 'FMNL1,', 'DUSP7', and, 'TRPM2', may, be, useful, markers, for, predicting, tumor, metastasis, and, therapeutic]), verbo([targets]), complemento([for, the, treatment, of, 'OS', patients, with, metastasis])]). relacion([sujeto(['It']), verbo([has]), complemento([long, been, considered, that, 'intron-containing', '(', 'spliced)', mRNAs, are, translationally, more, active, than, intronless, mRNAs, '(', identical, mRNA, not, produced, by, 'splicing)'])]). relacion([sujeto(['Here,', we, demonstrate, the, previously, unappreciated, role, of, eukaryotic, translation, initiation, factor, 4, 'AIII', '(', 'eIF4AIII),', a, component, of, 'EJC,', in, the, translation, of, mRNAs]), verbo([bound]), complemento([by, the, nuclear, 'cap-binding', complex, '(', 'CBC),', a, heterodimer, of, 'cap-binding', protein, 80, '(', 'CBP80)', and, 'CBP20'])]). relacion([sujeto([eIF4AIII, is]), verbo([recruited]), complemento([to, the, 5, '\'', -, end, of, mRNAs, bound, by, the, 'CBC', by, direct, interaction, with, the, 'CBC-dependent', translation, initiation, factor, '(', 'CTIF);', this, recruitment, of, eIF4AIII, is, independent, of, the, presence, of, introns, '(', deposited, 'EJCs', after, 'splicing)'])]). relacion([sujeto(['Polysome', 'fractionation,', tethering, 'experiments,', and, in, vitro, reconstitution, experiments, using, recombinant, proteins, show, that, eIF4AIII]), verbo([promotes]), complemento([efficient, unwinding, of, secondary, structures, in, 5, '\'', 'UTR,', and, consequently, enhances, 'CBC-dependent', translation, in, vivo, and, in, vitro])]). relacion([sujeto(['Therefore,', our, data]), verbo([provide]), complemento([evidence, that, eIF4AIII, is, a, specific, translation, initiation, factor, for, 'CBC-dependent', translation])]). relacion([sujeto(['We']), verbo([provide]), complemento([evidence, that, 'S6', kinase, 1, '(', 'S6K1)', 'Aly/REF-like', target, '(', 'SKAR)', is, engaged, in, 'IFN-α', signaling, and, plays, a, key, role, in, the, generation, of, 'IFN', responses])]). relacion([sujeto(['Our', data, demonstrate, that, 'IFN-α']), verbo([induces]), complemento([phosphorylation, of, 'SKAR,', which, is, mediated, by, either, the, p90, ribosomal, protein, 'S6', kinase, '(', 'RSK)', or, p70, 'S6', kinase, '(', 'S6K1),', in, a, cell, 'type-specific', manner])]). relacion([sujeto(['This', type, 'I', 'IFN-inducible', phosphorylation, of, 'SKAR', results, in]), verbo([enhanced]), complemento([interaction, with, the, eukaryotic, initiation, factor, '(', 'eIF)4G', and, recruitment, of, activated, 'RSK1', to, 5, '\'', cap, mRNA])]). relacion([sujeto(['Our', studies, also, establish, that, 'SKAR', is, present, in, 'cap-binding', 'CBP80', immune, complexes, and, that, this, interaction, is]), verbo([mediated]), complemento([by, eIF4G])]). relacion([sujeto(['We', demonstrate, that, inducible, protein, expression, of, key, 'IFN-α-regulated', protein, products, such, as, 'ISG15', and, 'p21(WAF1/CIP1)']), verbo([requires]), complemento(['SKAR', activity])]). relacion([sujeto(['Histone', biogenesis, is, tightly, controlled, at, multiple, steps, to]), verbo([maintain]), complemento([the, balance, between, the, amounts, of, 'DNA', and, histone, protein, during, the, cell, cycle])]). relacion([sujeto(['Here,', we, investigate, remodeling, of, 'stem-loop']), verbo([binding]), complemento([protein, '(', 'SLBP)-containing', histone, mRNPs, occurring, during, the, switch, from, the, actively, translating, mode, to, the, degradation, mode])]). relacion([sujeto(['This', disruption, is]), verbo([mediated]), complemento([by, competition, between, 'CTIF', and, 'UPF1', for, 'SLBP', binding])]). relacion([sujeto(['Further', characterizations]), verbo([reveal]), complemento([hyperphosphorylation, of, 'UPF1', by, activated, 'ATR', and, 'DNA-dependent', protein, kinase, upon, the, inhibition, of, 'DNA', replication, interacts, with, 'SLBP', more, 'strongly,', promoting, the, release, of, 'CTIF', and, eIF3, from, 'SLBP-containing', histone, mRNP])]). relacion([sujeto(['In', 'addition,', hyperphosphorylated, 'UPF1']), verbo([recruits]), complemento(['PNRC2', and, 'SMG5,', triggering, decapping, followed, by, 5, '\'', -, 'to-3\'', degradation, of, histone, mRNAs])]). relacion([sujeto(['The', collective, observations]), verbo([suggest]), complemento([that, both, inhibition, of, translation, and, recruitment, of, mRNA, degradation, machinery, during, histone, mRNA, degradation, are, tightly, coupled, and, coordinately, regulated, by, 'UPF1', phosphorylation])]). relacion([sujeto(['Histone', messenger, 'RNA', '(', 'mRNA)', levels, strongly]), verbo([increase]), complemento([during, early, 'S-phase', and, rapidly, decrease, at, the, end, of, it])]). relacion([sujeto(['The', degradation, is]), verbo([induced]), complemento([by, 3, '\'', end, additions, of, untemplated, 'uridines,', performed, by, terminal, uridyl, transferases])]). relacion([sujeto(['Such', 3, '\'', oligouridylated, transcripts, are, preferentially]), verbo([bound]), complemento([by, the, heteroheptameric, 'LSM1-7', 'complex,', which, also, interacts, with, the, 3, '\'', '→5\'', exonuclease, 'ERI1', '(', also, called, 3, '\'', 'hExo)'])]). relacion([sujeto(['Although', histone, mRNA, decay, is, now, known, in, some, 'detail,', important, questions, remain, 'open:', 'How', is, ceasing]), verbo([nuclear]), complemento(['DNA', replication, relayed, to, the, cytoplasmic, histone, mRNA, 'degradation?', 'Why', is, translation, important, for, this, 'process?', 'Recent', research, on, factors, such, as, 'SLIP1,', 'DBP5,', 'eIF3,', 'CTIF,', 'CBP80/20,', and, 'ERI1', has, provided, new, insights, into, the, 3, '\'', end, 'formation,', the, nuclear, 'export,', and, the, translation, of, histone, mRNAs])]). relacion([sujeto(['The', 'cap-binding', proteins, 'CBP20', and, 'CBP80']), verbo([have]), complemento(['well-established', roles, in, 'RNA', metabolism, and, plant, growth, and, development])]). relacion([sujeto(['Although', these, proteins, are, thought, to, be]), verbo([involved]), complemento([in, the, 'plant\'s', response, to, environmental, 'stress,', their, functions, in, this, process, are, unclear])]). relacion([sujeto(['Here', we, demonstrated, that, 'Arabidopsis', cbp20, and, cbp80, null, mutants, had, abnormal, leaves, and, flowers, and, exhibited]), verbo([increased]), complemento([sensitivity, to, salt, stress])]). relacion([sujeto(['Quantification', by, iTRAQ, '(', isobaric, tags, for, relative, and, absolute, 'quantification)', identified, 77, differentially]), verbo([expressed]), complemento([proteins, in, the, cbp20, and, cbp80, lines, compared, with, the, 'wild-type', 'Col-0', under, salt, stress, conditions])]). relacion([sujeto(['Most', of, these, differentially]), verbo([expressed]), complemento([proteins, were, synergistically, expressed, in, cbp20, and, 'cbp80,', suggesting, that, 'CBP20', and, 'CBP80', have, synergistic, roles, during, the, salt, stress, response])]). relacion([sujeto(['Biochemical', analysis, demonstrated, that, 'CBP20', and, 'CBP80', physically]), verbo([interacted]), complemento([with, each, other])]). relacion([sujeto(['Further', analysis, revealed, that, 'CBP20/80']), verbo([regulated]), complemento([the, splicing, of, genes, involved, in, proline, and, sugar, metabolism, and, that, the, epigenetic, and, 'post-translational', modifications, of, these, genes, were, involved, in, salt, stress, tolerance])]). relacion([sujeto(['Our', data]), verbo([suggest]), complemento([a, link, between, 'CBP20/80-dependent', protein, 'ubiquitination/sumoylation', and, the, salt, stress, response])]). relacion([sujeto(['Menin']), verbo([interacts]), complemento([with, several, transcription, 'factors,', including, 'JunD,', and, inhibits, their, activities])]). relacion([sujeto(['However,', the, precise, mechanism, by, which, menin]), verbo([suppresses]), complemento([gene, expression, is, not, well, understood])]). relacion([sujeto(['Here,', we, show, that, menin]), verbo([interacts]), complemento([with, 'arsenite-resistant', protein, 2, '(', 'ARS2),', a, component, of, the, nuclear, 'RNA', 'CAP-binding', complex, that, is, crucial, for, biogenesis, of, certain, miRNAs, including, 'let-7a'])]). relacion([sujeto(['The', levels, of, 'primary-let-7a', '(', 'pri-let-7a)', are, not, affected, by, 'menin;', 'however,', the, levels, of, mature, 'let-7a', are, substantially]), verbo([decreased]), complemento([upon, 'Men1', excision])]). relacion([sujeto(['Inhibition', of, 'let-7a', using, 'anti-miRNA', in, wild, type, cells, is, sufficient, to]), verbo([enhance]), complemento([the, expression, of, insulin, receptor, substrate, 2, '(', 'IRS2)', to, levels, observed, in, 'Men1-excised', cells])]). relacion([sujeto(['Ars2', knockdown]), verbo([decreased]), complemento(['let-7a', processing, in, 'menin-expressing', cells, but, had, little, impact, on, 'let-7a', levels, in, 'menin-excised', cells])]). relacion([sujeto(['As', 'IRS2', is, known, to]), verbo([mediate]), complemento([insulin, signaling, and, 'insulin/mitogen-induced', cell, 'proliferation,', these, findings, collectively, unravel, a, novel, mechanism, whereby, menin, suppresses, cell, 'proliferation,', at, least, partly, by, promoting, the, processing, of, certain, 'miRNAs,', including, 'let-7a,', leading, to, suppression, of, 'Irs2', expression, and, insulin, signaling])]). relacion([sujeto(['Drosha', is, the, main, 'RNase', 'III-like', enzyme]), verbo([involved]), complemento([in, the, process, of, microRNA, '(', 'miRNA)', biogenesis, in, the, nucleus])]). relacion([sujeto(['Using', 'whole-genome', 'ChIP-on-chip', 'analysis,', we, demonstrate, 'that,', in, addition, to, miRNA, 'sequences,', 'Drosha', specifically]), verbo([binds]), complemento(['promoter-proximal', regions, of, many, human, genes, in, a, 'transcription-dependent', manner])]). relacion([sujeto(['This']), verbo([binding]), complemento([is, not, associated, with, miRNA, production, or, 'RNA', cleavage])]). relacion([sujeto(['Furthermore,', we, show, that, this, function, of, 'Drosha', is, dependent, on, its, 'N-terminal', 'protein-interaction', 'domain,', which]), verbo([associates]), complemento([with, the, 'RNA-binding', protein, 'CBP80', and, 'RNA', 'Polymerase', 'II'])]). relacion([sujeto(['How', alternative, splicing, '(', 'AS)', is]), verbo([regulated]), complemento([in, plants, has, not, yet, been, elucidated])]). relacion([sujeto(['Previously,', we]), verbo([have]), complemento([shown, that, the, nuclear, 'cap-binding', protein, complex, '(', 'AtCBC)', is, involved, in, 'AS', in, 'Arabidopsis', thaliana])]). relacion([sujeto(['Here', we, show, that, both, subunits, of, 'AtCBC', '(', 'AtCBP20', and, 'AtCBP80)']), verbo([interact]), complemento([with, 'SERRATE', '(', 'AtSE),', a, protein, involved, in, the, microRNA, biogenesis, pathway])]). relacion([sujeto(['Moreover,', using, a, 'high-resolution', reverse, 'transcriptase-polymerase', chain, reaction, 'AS', system, we]), verbo([have]), complemento([found, that, 'AtSE', influences, 'AS', in, a, similar, way, to, the, 'cap-binding', complex, '(', 'CBC),', preferentially, affecting, selection, of, 5, '\'', splice, site, of, first, introns])]). relacion([sujeto(['The', 'AtSE', protein]), verbo([acts]), complemento([in, cooperation, with, 'AtCBC:', many, changes, observed, in, the, mutant, lacking, the, correct, 'SERRATE', activity, were, common, to, those, observed, in, the, cbp, mutants])]). relacion([sujeto(['The', histone, 'RNA-binding', protein, 'HBP/SLBP', '(', 'hairpin-binding', 'protein/stem-loop']), verbo([binding]), complemento(['protein),', an, essential, regulator, of, histone, gene, 'expression,', binds, to, the, conserved, hairpin, structure, located, in, the, 3, '\'', 'UTR', '(', untranslated, 'region)', of, histone, mRNA, and, participates, in, histone, 'pre-mRNA', 'processing,', translation, and, histone, mRNA, degradation])]). relacion([sujeto(['Here,', we]), verbo([report]), complemento([the, accumulation, of, alternatively, spliced, 'HBP/SLBP', transcripts, lacking, exons, 2, 'and/or', 3, &, 'nbsp;in', 'HeLa', cells, exposed, to, replication, stress])]). relacion([sujeto(['HBP/SLBP', mRNA, alternative, splicing, returned, to, low, levels, again, upon, removal, of, replication, stress, and, was, abrogated, by, 'caffeine,']), verbo([suggesting]), complemento([the, involvement, of, checkpoint, kinases])]). relacion([sujeto(['Analysis', of, 'HBP/SLBP', cellular, localization, using, 'GFP', '(', green, fluorescent, 'protein)', fusion, proteins, revealed, that, 'HBP/SLBP', protein, and, isoforms, lacking, the, domains, encoded, by, exon, 2, and, exons, 2, and, 3, were]), verbo([found]), complemento([in, the, nucleus, and, 'cytoplasm,', whereas, 'HBP/SLBP', lacking, the, domain, encoded, by, exon, 3, was, predominantly, localised, to, the, nucleus])]). relacion([sujeto(['This', isoform, lacks, the]), verbo([conserved]), complemento([region, important, for, 'protein-protein', interaction, with, the, 'CTIF', '[', 'CBP80/20', '(', 'cap-binding', protein, 80, /, 20, ')', ']', -, dependent, initiation, translation, factor, and, the, eIF4E, '(', eukaryotic, initiation, factor, '4E)-dependent', translation, factor, 'SLIP1/MIF4GD', '(', 'SLBP-interacting', protein, 1, /, 'MIF4G', 'domain)'])]). relacion([sujeto(['Consistent', with, 'this,', we]), verbo([have]), complemento([previously, demonstrated, that, this, region, is, required, for, the, function, of, 'HBP/SLBP', in, 'cap-dependent', translation])]). relacion([sujeto(['In', 'conclusion,', alternative, splicing, allows, the, synthesis, of, 'HBP/SLBP', isoforms, with, different, properties, that, may, be, important, for]), verbo([regulating]), complemento(['HBP/SLBP', functions, during, replication, stress])]). relacion([sujeto(['This', specialized, 3, '\'', end, is]), verbo([bound]), complemento([by, 'stem-loop', binding, protein, '(', 'SLBP),', a, protein, that, participates, in, the, nuclear, export, and, translation, of, histone, mRNAs])]). relacion([sujeto(['The', translational, activity, of, 'SLBP', is]), verbo([mediated]), complemento([by, interaction, with, 'SLIP1,', a, middle, domain, of, initiation, factor, 4, 'G', '(', 'MIF4G)-like', protein, that, connects, to, translation, initiation])]). relacion([sujeto(['We', determined, the, 2.5, 'Å', resolution, crystal, structure, of, zebrafish, 'SLIP1']), verbo([bound]), complemento([to, the, 'translation-activation', domain, of, 'SLBP', and, identified, the, determinants, of, the, recognition])]). relacion([sujeto(['We', confirmed, the]), verbo([binding]), complemento([of, 'SLIP1', to, 'DBP5', and, eIF3g, by, 'pull-down', assays, and, determined, the, 3.25, 'Å', resolution, structure, of, 'SLIP1', bound, to, the, 'DBP5', 'SBM'])]). relacion([sujeto(['The', 'SBM-binding', and, homodimerization, residues, of, 'SLIP1', are]), verbo([conserved]), complemento([in, the, 'MIF4G', domain, of, 'CBP80/20-dependent', translation, initiation, factor, '(', 'CTIF)'])]). relacion([sujeto(['The', results]), verbo([suggest]), complemento([how, the, 'SLIP1', homodimer, or, a, 'SLIP1-CTIF', heterodimer, can, function, as, platforms, to, bridge, 'SLBP', with, 'SBM-containing', proteins, involved, in, different, steps, of, mRNA, metabolism])]). relacion([sujeto(['The', elaborate, mechanism, of, miRNA, biogenesis]), verbo([involves]), complemento([transcription, and, multiple, processing, steps])]). relacion([sujeto(['Here,', we]), verbo([report]), complemento([the, identification, of, a, pair, of, evolutionarily, conserved, 'NOT2_3_5', 'domain-containing-proteins,', 'NOT2a', and, 'NOT2b', '(', previously, known, as, 'At-Negative', on, 'TATA', less2, '[', 'NOT2]', and, 'VIRE2-INTERACTING', 'PROTEIN2,', 'respectively),', as, components, involved, in, 'Arabidopsis', thaliana, miRNA, biogenesis])]). relacion([sujeto(['NOT2', was, identified, by, its, interaction, with, the, 'Piwi/Ago/Zwille', domain, of, 'DICER-LIKE1', '(', 'DCL1),', an, interaction, that, is]), verbo([conserved]), complemento([between, rice, '(', 'Oryza', 'sativa)', and, 'Arabidopsis', thaliana])]). relacion([sujeto(['Inactivation', of, both, 'NOT2', genes, in, 'Arabidopsis']), verbo([caused]), complemento([severe, defects, in, male, 'gametophytes,', and, weak, lines, show, pleiotropic, defects, reminiscent, of, miRNA, pathway, mutants])]). relacion([sujeto(['Impairment', of, 'NOT2s']), verbo([decreases]), complemento([the, accumulation, of, primary, miRNAs, and, mature, miRNAs, and, affects, 'DCL1', but, not, 'HYPONASTIC', 'LEAVES1', '(', 'HYL1)', localization, in, vivo])]). relacion([sujeto(['In', 'addition,', 'NOT2b', protein]), verbo([interacts]), complemento([with, polymerase, 'II', and, other, miRNA, processing, 'factors,', including, two, cap, binding, 'proteins,', 'CBP80/ABH1,', 'CBP20,', and, 'SERRATE', '(', 'SE)'])]). relacion([sujeto(['Finally,', we]), verbo([found]), complemento([that, the, mRNA, levels, of, some, protein, coding, genes, were, also, affected])]). relacion([sujeto(['Therefore,', these, results]), verbo([suggest]), complemento([that, 'NOT2', proteins, act, as, general, factors, to, promote, the, transcription, of, protein, coding, as, well, as, miRNA, genes, and, facilitate, efficient, 'DCL1', recruitment, in, miRNA, biogenesis])]). relacion([sujeto(['MicroRNAs', '(', 'miRNAs)', are, small, regulatory, 'RNAs', that]), verbo([have]), complemento([important, regulatory, roles, in, numerous, developmental, and, metabolic, processes, in, most, eukaryotes])]). relacion([sujeto(['In', 'Arabidopsis,', 'DICER-LIKE1', '(', 'DCL1),', 'HYPONASTIC', 'LEAVES', 1, ',', 'SERRATE,', 'HUA', 'ENHANCER1', and, 'HASTY', are]), verbo([involved]), complemento([in, processing, of, primary, miRNAs, '(', 'pri-miRNAs)', to, yield, precursor, miRNAs, '(', 'pre-miRNAs)', and, eventually, miRNAs])]). relacion([sujeto(['In', addition, to, these, 'components,', mRNA, 'cap-binding', 'proteins,', 'CBP80/ABA', 'HYPERSENSITIVE1', and, 'CBP20,', also]), verbo([participate]), complemento([in, miRNA, biogenesis])]). relacion([sujeto(['Here,', we, show, that, 'STABILIZED1', '(', 'STA1),', an, 'Arabidopsis', 'pre-mRNA', processing, factor, 6, 'homolog,', is, also]), verbo([involved]), complemento([in, the, biogenesis, of, miRNAs])]). relacion([sujeto(['The', dramatic, reductions, of, mature, miRNAs, were]), verbo([associated]), complemento([with, the, accumulation, of, their, target, gene, transcripts, and, developmental, defects])]). relacion([sujeto(['Furthermore,', 'sta1-1', impaired, splicing, of, intron, containing, 'pri-miRNAs', and]), verbo([decreased]), complemento([transcript, levels, of, 'DCL1'])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, 'STA1', is, involved, in, miRNA, biogenesis, directly, by, functioning, in, 'pri-miRNA', splicing, and, indirectly, by, modulating, the, 'DCL1', transcript, level])]). relacion([sujeto(['Here,', using, a, yeast, 'two-hybrid', screening, 'system,', we, identify, a, 'stem-loop']), verbo([binding]), complemento([protein, '(', 'SLBP)', that, binds, to, a, 'stem-loop', structure, at, the, 3, '\'', -, end, of, the, 'replication-dependent', histone, mRNA, as, a, 'CT', initiation, factor, '(', 'CTIF)-interacting', protein])]). relacion([sujeto(['SLBP', preferentially]), verbo([associates]), complemento([with, the, 'CT', complex, of, histone, 'mRNAs,', but, not, with, the, 'eIF4E-depedent', translation, '(', 'ET)', complex])]). relacion([sujeto(['Several', lines, of, evidence, indicate, that, rapid, degradation, of, histone, mRNA, on, the, inhibition, of, 'DNA', replication, largely, takes, place, during, 'CT', and, not, 'ET,', which]), verbo([has]), complemento([been, previously, unappreciated])]). relacion([sujeto(['The', collective, findings]), verbo([suggest]), complemento([that, mRNAs, harboring, a, different, 3, '\'', -, end, use, a, different, mechanism, of, translation, 'initiation,', expanding, the, repertoire, of, 'CT', as, a, step, for, determining, the, fate, of, histone, mRNAs])]). relacion([sujeto(['Developing', new, strategies, for, crop, plants, to]), verbo([respond]), complemento([to, drought, is, crucial, for, their, innovative, breeding])]). relacion([sujeto(['The', 'down-regulation', of]), verbo([nuclear]), complemento(['cap-binding', proteins, in, 'Arabidopsis', renders, plants, drought, tolerant])]). relacion([sujeto(['The', 'CBP80', gene, in, the, potato]), verbo([cultivar]), complemento(['Desiree', was, silenced, using, artificial, microRNAs])]). relacion([sujeto(['Transgenic', plants, displayed, a, higher, tolerance, to, 'drought,', 'ABA-hypersensitive', stomatal, 'closing,', an]), verbo([increase]), complemento([in, leaf, stomata, and, trichome, 'density,', and, compact, cuticle, structures, with, a, lower, number, of, microchannels])]). relacion([sujeto(['The', level, of, miR159, was, 'decreased,', and, the, levels, of, its]), verbo([target]), complemento([mRNAs, 'MYB33', and, 'MYB101', increased, in, the, transgenic, plants, subjected, to, drought])]). relacion([sujeto(['The', evolutionary, conservation, of, 'CBP80,', a, gene, that, plays, a, role, in, the, response, to, 'drought,']), verbo([suggests]), complemento([that, it, is, a, candidate, for, genetic, manipulations, that, aim, to, obtain, improved, 'water-deficit', tolerance, of, crop, plants])]). relacion([sujeto(['The', mRNA, export, complex, 'TREX', '(', 'TREX)', is, known, to, contain, 'Aly,', 'UAP56,', 'Tex1', and, the, 'THO', 'complex,', among, which, 'UAP56', is]), verbo([required]), complemento([for, 'TREX', assembly])]). relacion([sujeto(['We']), verbo([found]), complemento([that, 'Tex1', is, essentially, a, subunit, of, the, 'THO', complex])]). relacion([sujeto(['Aly,', 'THO', and, 'UAP56', are, all]), verbo([required]), complemento([for, assembly, of, 'TREX,', in, which, 'Aly', directly, interacts, with, 'THO', subunits, 'Thoc2', and, 'Thoc5'])]). relacion([sujeto(['Interestingly,', association, of, 'UAP56', with, the, spliced, 'mRNA,', but, not, with, the, 'pre-mRNA,']), verbo([requires]), complemento(['Aly', and, 'THO'])]). relacion([sujeto(['Unexpectedly,', we]), verbo([found]), complemento([that, 'Aly', and, 'THO', require, each, other, to, associate, with, the, spliced, mRNA])]). relacion([sujeto(['Together,', we, propose, that, 'Aly,', 'THO', and, 'UAP56', form, a, highly, integrated, unit, to]), verbo([associate]), complemento([with, the, spliced, mRNA, and, function, in, mRNA, export])]). relacion([sujeto(['Although', the, importance, of, abscisic, acid, '(', 'ABA)', in, plant, development, and, response, to, abiotic, and, biotic, stresses, is, well, 'recognized,', the, molecular, basis, of, the, signaling, pathway]), verbo([has]), complemento([not, been, fully, elucidated])]). relacion([sujeto(['Mutants', in, genes, related, to, 'ABA', are, widely, used, as, a, tool, for]), verbo([gained]), complemento([insight, into, the, mechanisms, of, 'ABA', signal, transduction, and, 'ABA-dependent', stress, response])]). relacion([sujeto(['The', molecular, analysis, revealed, that, mutation]), verbo([causing]), complemento([the, phenotype, of, soa1, occurred, in, the, 'ABI4', '(', 'ABA', insensitive, 4, ')', gene])]). relacion([sujeto(['Analysis', of, 'pre-miR159', 'expression,', whose, processing, depends, on, 'CBC,', as, well, as]), verbo([targets]), complemento([of, 'miR159:', 'MYB33', and, 'MYB101,', which, are, positive, regulators, of, 'ABA', 'signaling,', revealed, a, possible, link, between, 'CBP80', '(', 'ABH1)', and, 'ABI4', presented, here])]). relacion([sujeto(['Long', intergenic, noncoding, 'RNAs', '(', 'lincRNAs)']), verbo([transcribed]), complemento([from, intergenic, regions, of, yeast, and, animal, genomes, play, important, roles, in, key, biological, processes])]). relacion([sujeto(['Yet,', plant, lincRNAs, remain, poorly, characterized, and, how, lincRNA, biogenesis, is]), verbo([regulated]), complemento([is, unclear])]). relacion([sujeto(['Transcriptome', profiling, by, custom, microarrays, revealed, that, the, majority, of, these, lincRNAs, are]), verbo([expressed]), complemento([at, a, level, between, those, of, mRNAs, and, precursors, of, miRNAs])]). relacion([sujeto(['MicroRNAs', '(', 'miRNAs)', are, key, regulators, of, gene, expression, and, play, critical, roles, in]), verbo([modulating]), complemento(['metabolism,', development, and, physiology, in, animals, and, plants])]). relacion([sujeto(['Recent', studies]), verbo([have]), complemento([shown, that, 'RNA-binding', proteins, play, important, roles, in, producing, miRNAs, by, affecting, the, accurate, 'and/or', efficient, processing, of, precursors, of, miRNAs])]). relacion([sujeto(['Many', of, these, 'RNA-binding', proteins, also]), verbo([have]), complemento([roles, in, general, 'RNA', 'metabolism,', indicating, potential, connections, between, miRNA, biogenesis, and, other, 'RNA', metabolism])]). relacion([sujeto(['SAGA/TFTC', is, a, histone, acetyltransferase, complex, that]), verbo([has]), complemento([a, second, enzymatic, activity, because, of, the, presence, of, a, deubiquitination, module, '(', 'DUBm)'])]). relacion([sujeto(['We', show, that, 'Sgf11']), verbo([has]), complemento([other, 'DUBm-independent', functions])]). relacion([sujeto(['It']), verbo([associates]), complemento([with, 'Cbp80', component, of, the, 'cap-binding', complex, and, is, thereby, recruited, onto, growing, messenger, ribonucleic, acid, '(', 'mRNA);', it, also, interacts, with, the, 'AMEX', mRNA, export, complex, and, is, essential, for, hsp70, mRNA, 'export,', as, well, as, for, general, mRNA, export, from, the, nucleus])]). relacion([sujeto(['The', first, round, of, translation, occurs, on, mRNAs]), verbo([bound]), complemento([by, nuclear, 'cap-binding', complex, '(', 'CBC),', which, is, composed, of, nuclear, 'cap-binding', protein, 80, and, 20, '(', 'CBP80/20)'])]). relacion([sujeto(['During', this, round, of, 'translation,', aberrant, mRNAs, are]), verbo([recognized]), complemento([and, downregulated, in, abundance, by, 'nonsense-mediated', mRNA, decay, '(', 'NMD),', which, is, one, of, the, mRNA, quality, control, mechanisms])]). relacion([sujeto(['Here,', our, microarray, analysis]), verbo([reveals]), complemento([that, the, level, of, 'cyclin-dependent', kinase, inhibitor, 1, 'A', '(', 'CDKN1A;', also, known, as, 'Waf1/p21)', mRNAs, increases, in, cells, depleted, of, cellular, 'NMD', factors])]). relacion([sujeto(['Using', chimeric, reporter, 'constructs,', we]), verbo([find]), complemento([that, the, uORF, of, 'CDKN1A', mRNA, negatively, modulates, translation, of, the, main, downstream, 'ORF'])]). relacion([sujeto(['These', findings]), verbo([provide]), complemento([biological, insights, into, the, possible, role, of, 'NMD', in, diverse, biological, pathways, mediated, by, 'CDKN1A'])]). relacion([sujeto(['Here,', we, show, that, 'CBP80/20-dependent', translation, initiation, factor, '(', 'CTIF),', which]), verbo([has]), complemento([been, shown, to, be, preferentially, involved, in, 'CT', but, not, 'ET,', specifically, interacts, with, 'eIF3g,', a, component, of, the, eIF3, complex, involved, in, ribosome, recruitment])]). relacion([sujeto(['By']), verbo([interacting]), complemento([with, 'eIF3g,', 'CTIF', serves, as, an, adaptor, protein, to, bridge, the, 'CBP80/20', and, the, eIF3, 'complex,', leading, to, efficient, ribosome, recruitment, during, 'CT'])]). relacion([sujeto(['Accordingly,', 'down-regulation', of, 'CTIF', using, a, small, interfering, 'RNA']), verbo([causes]), complemento([a, redistribution, of, 'CBP80', from, polysome, fractions, to, subpolysome, 'fractions,', without, significant, consequence, to, eIF4E, distribution])]). relacion([sujeto(['In', 'addition,', 'down-regulation', of, eIF3g]), verbo([inhibits]), complemento([the, efficiency, of, 'nonsense-mediated', mRNA, 'decay,', which, is, tightly, coupled, to, 'CT', but, not, to, 'ET'])]). relacion([sujeto(['Translation', is, a]), verbo([regulated]), complemento([process, and, is, pivotal, to, proper, cell, growth, and, homeostasis])]). relacion([sujeto(['HIV-1', infection]), verbo([arrests]), complemento([the, cell, cycle, in, the, 'G2/M', 'phase,', potentially, disrupting, the, regulation, of, host, cell, translation])]). relacion([sujeto(['In', this, 'study,', we, present, evidence, that, 'HIV-1', infection, downregulates, translation, in, 'lymphocytes,', attributable, to, the, cell, cycle]), verbo([arrest]), complemento([induced, by, the, 'HIV-1', accessory, protein, 'Vpr'])]). relacion([sujeto(['RNA-coimmunoprecipitation', assays, determined, that, the, 'HIV-1', unspliced, and, singly, spliced, transcripts, are, predominantly]), verbo([associated]), complemento([with, nuclear, cap, binding, protein, 80, '(', 'CBP80)', in, contrast, to, 'completely-spliced', viral, and, cellular, mRNAs, that, are, associated, with, eIF4E])]). relacion([sujeto(['The', active, translation, of, the]), verbo([nuclear]), complemento([cap, binding, complex, '(', 'CBC)-bound', viral, mRNAs, is, demonstrated, by, ribosomal, 'RNA', profile, analyses])]). relacion([sujeto(['Thus,', our, findings]), verbo([have]), complemento([uncovered, that, the, maintenance, of, 'CBC', association, is, a, novel, mechanism, used, by, 'HIV-1', to, bypass, downregulation, of, eIF4E, activity, and, sustain, viral, protein, synthesis])]). relacion([sujeto(['Control', of, mRNA, translation, plays, a, critical, role, in, cell, 'growth,', 'proliferation,', and, differentiation, and, is, tightly]), verbo([regulated]), complemento([by, 'AKT', and, 'RAS', oncogenic, pathways])]). relacion([sujeto([eIF4E, contributes, to, malignancy, by, selectively, enabling, the, translation, of, a, limited, pool, of, mRNAs, that, generally, encode, key, proteins]), verbo([involved]), complemento([in, cell, cycle, 'progression,', 'angiogenesis,', and, metastasis])]). relacion([sujeto(['Several', data, indicate, that, the, inhibition, of, eIF4E, in, tumor, cell, lines, and, xenograft, models, impairs, tumor, growth, and]), verbo([induces]), complemento(['apoptosis;', 'eIF4E,', 'therefore,', can, be, considered, a, valuable, target, for, cancer, therapy])]). relacion([sujeto(['Targeting', the, 'cap-binding', pocket, of, eIF4E, should, represent, a, way, to]), verbo([inhibit]), complemento([all, the, eIF4E, cellular, functions])]). relacion([sujeto(['These', assays, could, support, 'high-throughput', 'screening,', further, 'refinement,', and, characterization, of, eIF4E, 'inhibitors,', as, well, as, selectivity, assessment, against, 'CBP80/CBP20,', the, other, major, 'cap-binding', complex, of, eukaryotic, 'cells,', overall]), verbo([providing]), complemento([a, robust, roadmap, for, development, of, 'eIF4E-specific', inhibitors])]). relacion([sujeto(['The', 'Swedish', mutation, of, amyloid, precursor, protein, '(', 'APP-sw)']), verbo([has]), complemento([been, reported, to, dramatically, increase, beta, amyloid, production, through, aberrant, cleavage, at, the, beta, secretase, 'site,', causing, 'early-onset', 'Alzheimer\'s', disease, '(', 'AD)'])]). relacion([sujeto(['DNA', methylation]), verbo([has]), complemento([been, reported, to, be, associated, with, 'AD', 'pathogenesis,', but, the, underlying, molecular, mechanism, of, 'APP-sw-mediated', epigenetic, alterations, in, 'AD', pathogenesis, remains, largely, unknown])]). relacion([sujeto(['To', identify, genes, whose, expression, was]), verbo([regulated]), complemento([by, 'DNA', methylation, 'status,', we, performed, integrated, analysis, of, 'CpG', methylation, and, mRNA, expression, 'profiles,', and, identified, three, target, genes, of, the, 'APP-sw', 'mutant;', hypomethylated, 'CTIF', '(', 'CBP80/CBP20-dependent', translation, initiation, 'factor)', and, 'NXT2', '(', nuclear, exporting, factor, 2, ')', ',', and, hypermethylated, 'DDR2', '(', discoidin, domain, receptor, 2, ')'])]). relacion([sujeto(['Nuclear', 'cap-binding', protein, '(', 'CBP)', 80, /, 20, -, dependent, translation, '(', 'CT)', is, one, of, the]), verbo([targets]), complemento([for, 'miRNA-mediated', gene, silencing])]). relacion([sujeto(['Here,', we]), verbo([provide]), complemento([evidence, that, human, argonaute, 2, '(', 'Ago2)', competes, with, 'CBP80/20', for, 'cap-association,', inhibiting, 'CT', and, thus, 'nonsense-mediated', mRNA, decay, '(', 'NMD),', which, is, tightly, coupled, to, 'CT'])]). relacion([sujeto(['Immunoprecipitation', using, 'CBP80', antibody]), verbo([reveals]), complemento([that, 'Ago2,', but, not, 'Ago2F2V2,', inhibits, the, binding, of, 'CBP80/20', to, cap, structure])]). relacion([sujeto(['Our', observations]), verbo([provide]), complemento([molecular, insight, into, the, 'cross-talk', between, 'miRNA-mediated', gene, 'silencing,', 'CT,', and, 'NMD'])]). relacion([sujeto(['Newly', synthesized, mRNPs]), verbo([bound]), complemento([by, the, 'cap-binding', protein, heterodimer, 'CBP80-CBP20', '(', 'CBC)', initially, undergo, a, pioneer, round, of, translation])]). relacion([sujeto(['One', purpose, of, this, round, of, translation, is, to]), verbo([ensure]), complemento([the, quality, of, gene, 'expression,', as, exemplified, by, 'nonsense-mediated', messenger, 'RNA', '(', 'mRNA)', decay, '(', 'NMD)'])]). relacion([sujeto(['NMD', largely, functions, to, eliminate, mRNAs, that, prematurely, terminate, 'translation,', although, 'NMD', also, contributes, to, proper, gene, 'control,', and, it]), verbo([targets]), complemento(['CBC-bound', mRNPs])]). relacion([sujeto(['Rather', than, supporting, 'NMD,', 'eIF4E-bound', mRNPs]), verbo([provide]), complemento([for, the, bulk, of, cellular, protein, synthesis, and, are, the, primary, targets, of, mRNA, decay, mechanisms, that, conditionally, regulate, gene, expression])]). relacion([sujeto(['The']), verbo([nuclear]), complemento(['cap-binding', complex, '(', 'CBC),', a, heterodimer, comprised, of, a, 20, kDa, subunit, '(', 'CBP20)', and, an, 80, kDa, regulatory, subunit, '(', 'CBP80),', binds, to, nascent, 'RNA', polymerase, 'II', transcripts, and, is, important, throughout, different, aspects, of, 'RNA', metabolism])]). relacion([sujeto(['In', a, recent, 'publication,', using, a, combination, of, 'X-ray', crystallographic, 'information,', mutagenesis, 'studies,', 'small-angle', scattering, 'experiments,', analytical, ultracentrifugation, and, in, vivo, 'assays,', we, presented, evidence, that, 'importin-α', and, 'importin-β,', two, nucleocytoplasmic, transport, 'proteins,', play, key, roles, in]), verbo([regulating]), complemento([the, binding, of, capped, 'RNA', by, the, 'CBC', in, cells])]). relacion([sujeto(['A', model, for, how, complexes, between, 'CBC', and, the, importins, cycle, in, and, out, of, the, nucleus, and, direct, the, proper, positional]), verbo([binding]), complemento([and, release, of, capped, 'RNA', is, presented, here, and, is, discussed, in, light, of, recent, publications])]). relacion([sujeto(['(', 2010, ')', show, that, the, 'cap-binding', protein, 'CBP80']), verbo([promotes]), complemento(['nonsense-mediated', decay, '(', 'NMD)', at, two, steps])]). relacion([sujeto(['In', this, dual, 'capacity,', 'CBP80', may, facilitate, essential, communication, between, the, premature, termination, codon, '(', 'PTC)', and, the, 'exon-junction', complex, '(', 'EJC)', to]), verbo([trigger]), complemento(['NMD'])]). relacion([sujeto(['This', round]), verbo([involves]), complemento([newly, synthesized, mRNA, that, is, bound, at, its, 5, '\'', end, by, the, 'cap-binding', protein, '(', 'CBP)', heterodimer, 'CBP80-CBP20'])]). relacion([sujeto(['Here', we, show, that, precluding, the]), verbo([binding]), complemento([of, the, 'NMD', factor, 'UPF1', to, 'CBP80', inhibits, 'NMD', at, two, 'steps:', the, association, of, 'SMG1', and, 'UPF1', with, the, two, eukaryotic, release, factors, '(', 'eRFs)', during, 'SURF', complex, formation, at, a, 'PTC,', and, the, subsequent, association, of, 'SMG1', and, 'UPF1', with, an, 'exon-junction', complex])]). relacion([sujeto(['We', also, demonstrate, that, 'UPF1']), verbo([binds]), complemento(['PTC-containing', mRNA, more, efficiently, than, the, corresponding, 'PTC-free', mRNA, in, a, way, that, is, promoted, by, the, 'UPF1-CBP80', interaction])]). relacion([sujeto(['Imperfect', 'base-pairing', between, microRNA, '(', 'miRNA)', and, the, 3, '\'', -, untranslated, region, of]), verbo([target]), complemento([messenger, 'RNA', '(', 'mRNA)', triggers, translational, repression, of, the, target, mRNA])]). relacion([sujeto(['Here,', we]), verbo([provide]), complemento([evidence, that, human, 'Argonaute', 2, targets, 'cap-binding', protein, '(', 'CBP)80/20-bound', mRNAs, and, exon, junction, 'complex-bound', mRNAs, and, inhibits, 'nonsense-mediated', mRNA, decay, '(', 'NMD),', which, is, restricted, tightly, to, 'CBP80/20-bound', mRNAs])]). relacion([sujeto(['Furthermore,', microarray, analyses]), verbo([reveal]), complemento([that, a, subset, of, cellular, 'transcripts,', which, are, expected, to, be, targeted, for, 'NMD,', is, stabilized, by, 'miRNA-mediated', gene, silencing])]). relacion([sujeto(['We', previously, showed, that, mRNA, 3, '\'', end, cleavage, reaction, in, cell, extracts, is, strongly, but, transiently]), verbo([inhibited]), complemento([under, 'DNA-damaging', conditions])]). relacion([sujeto(['The', cleavage, stimulation, 'factor-50', '(', 'CstF-50)']), verbo([has]), complemento([a, role, in, this, 'response,', providing, a, link, between, 'transcription-coupled', 'RNA', processing, and, 'DNA', repair])]). relacion([sujeto(['In', this, 'study,', we, show, that, 'CstF-50']), verbo([interacts]), complemento([with, nuclear, 'poly(A)-specific', ribonuclease, '(', 'PARN)', using, in, vitro, and, in, extracts, of, 'UV-exposed', cells])]). relacion([sujeto(['The', 'CstF-50/PARN', complex, formation]), verbo([has]), complemento([a, role, in, the, inhibition, of, 3, '\'', cleavage, and, activation, of, deadenylation, upon, 'DNA', damage])]). relacion([sujeto(['Extending', these, 'results,', we]), verbo([found]), complemento([that, the, tumour, suppressor, 'BARD1,', which, is, involved, in, the, 'UV-induced', inhibition, of, 3, '\'', 'cleavage,', strongly, activates, deadenylation, by, 'PARN', in, the, presence, of, 'CstF-50,', and, that, 'CstF-50/BARD1', can, revert, the, 'cap-binding', 'protein-80', '(', 'CBP80)-mediated', inhibition, of, 'PARN', activity])]). relacion([sujeto(['We', also]), verbo([provide]), complemento([evidence, that, 'PARN', along, with, the, 'CstF/BARD1', complex, participates, in, the, regulation, of, endogenous, transcripts, under, 'DNA-damaging', conditions])]). relacion([sujeto(['We', speculate, that, the, interplay, between, 'polyadenylation,', deadenylation, and, 'tumour-suppressor', factors, might]), verbo([prevent]), complemento([the, expression, of, prematurely, terminated, 'messengers,', contributing, to, control, of, gene, expression, under, different, cellular, conditions])]). relacion([sujeto(['The', pioneer, round, of, translation, uses, newly, synthesized, mRNA, that, is]), verbo([bound]), complemento([by, 'cap-binding', protein, 80, '(', 'CBP80)-CBP20', '(', also, known, as, the, 'cap-binding', complex, '[', 'CBC])', at, the, 'cap,', 'poly(A)-binding', protein, 'N1', '(', 'PABPN1)', and, 'PABPC1', at, the, 'poly(A)', 'tail,', 'and,', provided, biogenesis, involves, 'pre-mRNA', 'splicing,', exon, junction, complexes, '(', 'EJCs)', at, 'exon-exon', junctions])]). relacion([sujeto(['Subsequent', rounds, of, translation, engage, mRNA, that, is]), verbo([bound]), complemento([by, eukaryotic, translation, initiation, factor, '4E', '(', 'eIF4E)', at, the, cap, and, 'PABPC1', at, the, 'poly(A)', 'tail,', but, that, lacks, detectable, 'EJCs', and, 'PABPN1'])]). relacion([sujeto(['Using', the, level, of, intracellular, iron, to]), verbo([regulate]), complemento([the, translation, of, specific, 'mRNAs,', we, show, that, translation, promotes, not, only, removal, of, 'EJC', 'constituents,', including, the, eIF4AIII, 'anchor,', but, also, replacement, of, 'PABPN1', by, 'PABPC1'])]). relacion([sujeto(['Instead,', replacement, of, 'CBC', by, eIF4E, is]), verbo([promoted]), complemento([by, importin, beta, '(', 'IMPbeta):', 'Inhibiting', the, binding, of, 'IMPbeta', to, the, complex, of, 'CBC-IMPalpha', at, an, mRNA, cap, using, the, 'IMPalpha', 'IBB', '(', 'IMPbeta-binding)', domain, or, a, 'RAN', variant, increases, the, amount, of, 'CBC-bound', mRNA, and, decreases, the, amount, of, 'eIF4E-bound', mRNA])]). relacion([sujeto(['The']), verbo([nuclear]), complemento(['cap-binding', protein, complex, '(', 'CBC)', participates, in, 5, '\'', splice, site, selection, of, introns, that, are, proximal, to, the, mRNA, cap])]). relacion([sujeto(['However,', it, is, not, known, whether, 'CBC']), verbo([has]), complemento([a, role, in, alternative, splicing])]). relacion([sujeto(['Significant', changes, in, the, ratios, of, alternative, splicing, isoforms, were]), verbo([found]), complemento([in, 101, genes])]). relacion([sujeto(['The', 'cbp80(abh1)', and, 'cbp20/80', mutants, had, many, more, changes, in, alternative, splicing, in, common, than, did, cbp20, and, 'cbp20/80']), verbo([suggesting]), complemento([that, 'CBP80', plays, a, more, significant, role, in, alternative, splicing, than, 'CBP20,', probably, being, a, platform, for, interactions, with, other, splicing, factors])]). relacion([sujeto(['Cap-binding', proteins, and, the, 'CBC', are, therefore, directly]), verbo([involved]), complemento([in, alternative, splicing, of, some, 'Arabidopsis', genes, and, in, most, cases, influenced, alternative, splicing, of, the, first, 'intron,', particularly, at, the, 5, '\'', splice, site])]). relacion([sujeto(['The']), verbo([binding]), complemento([of, capped, 'RNAs', to, the, 'cap-binding', complex, '(', 'CBC)', in, the, 'nucleus,', and, their, dissociation, from, the, 'CBC', in, the, 'cytosol,', represent, essential, steps, in, 'RNA', processing])]). relacion([sujeto(['Here', we, show, how, the, nucleocytoplasmic, transport, proteins, 'importin-alpha', and, 'importin-beta']), verbo([have]), complemento([key, roles, in, regulating, these, events])]). relacion([sujeto(['As', a, first, step, toward, understanding, the, molecular, basis, for, this, 'regulation,', we, determined, a, 2.2, -, 'A', resolution, 'X-ray', structure, for, a, 'CBC-importin-alpha', complex, that]), verbo([provides]), complemento([a, detailed, picture, for, how, 'importin-alpha', binds, to, the, 'CBP80', subunit, of, the, 'CBC'])]). relacion([sujeto(['Through', a, combination, of, biochemical, 'studies,', 'X-ray', crystallographic, information, and, 'small-angle', scattering, 'experiments,', we, then, determined, how, 'importin-beta']), verbo([binds]), complemento([to, the, 'CBC', through, its, 'CBP20', subunit])]). relacion([sujeto(['Together,', these, studies, enable, us, to, propose, a, model, describing, how, 'importin-beta']), verbo([stimulates]), complemento([the, dissociation, of, capped, 'RNA', from, the, 'CBC', in, the, cytosol, following, its, nuclear, export])]). relacion([sujeto(['During', or, right, after, mRNA, export, via, the]), verbo([nuclear]), complemento([pore, complex, '(', 'NPC)', in, mammalian, 'cells,', mRNAs, undergo, translation, mediated, by, nuclear, 'cap-binding', proteins, 80, and, 20, '(', 'CBP80/20)'])]). relacion([sujeto(['Nonsense-mediated', mRNA, decay, '(', 'NMD),', one, of, the, 'best-characterized', mRNA, surveillance, 'mechanisms,']), verbo([has]), complemento([been, shown, to, occur, on, 'CBP80/20-bound', mRNAs])]). relacion([sujeto(['However,', despite, the, tight, link, between, 'CBP80/20-dependent', translation, and, 'NMD,', the, underlying, molecular, mechanism, and, cellular, factors, that]), verbo([mediate]), complemento(['CBP80/20-dependent', translation, remain, obscure])]). relacion([sujeto(['CTIF']), verbo([interacts]), complemento([directly, with, 'CBP80', and, is, part, of, the, 'CBP80/20-dependent', translation, initiation, complex])]). relacion([sujeto(['Here', we, identify, a, component, of, the]), verbo([nuclear]), complemento(['RNA', 'cap-binding', complex, '(', 'CBC),', 'Ars2,', that, is, important, for, miRNA, biogenesis, and, critical, for, cell, proliferation])]). relacion([sujeto(['Deletion', of, 'Ars2', is, developmentally, 'lethal,', and, deletion, in, adult, mice]), verbo([led]), complemento([to, bone, marrow, failure, whereas, parenchymal, organs, composed, of, nonproliferating, cells, were, unaffected])]). relacion([sujeto(['Depletion', of, 'Ars2', or, 'CBP80', from, proliferating, cells, impaired, 'miRNA-mediated', repression, and]), verbo([led]), complemento([to, alterations, in, primary, miRNA, processing, in, the, nucleus])]). relacion([sujeto(['These', findings]), verbo([provide]), complemento([evidence, for, a, role, for, 'Ars2', in, 'RNA', interference, regulation, during, cell, proliferation])]). relacion([sujeto(['Translation', of, most, mRNAs, is, performed, in, a, 'cap-dependent', 'manner,']), verbo([requiring]), complemento([a, protein, 'complex,', the, cap, 'complex,', to, regulate, the, accessibility, of, the, message, to, the, 40, 'S', ribosome])]). relacion([sujeto(['The', cap, complex, initiates, protein, translation, by]), verbo([binding]), complemento([to, the, 5, '\'', cap, of, an, mRNA, and, recruiting, ribosomes, to, begin, translation])]). relacion([sujeto(['Here,', we, purified, proteins, that]), verbo([bind]), complemento([to, the, 5, '\'', cap, during, the, 'Arabidopsis', growth, cycle])]). relacion([sujeto(['Using', 'Western', 'blotting,', the, cap, complexes, of, quiescent, cells, were]), verbo([found]), complemento([to, be, composed, of, only, three, major, 'proteins:', 'eIF4isoE,', which, is, primarily, a, cytoplasmic, 'protein,', and, eIF4E, and, 'CBP80,', which, accumulate, in, the, nucleus])]). relacion([sujeto(['However,', when, cells, 'proliferate,', at, least, 10, major, proteins]), verbo([bind]), complemento([directly, or, indirectly, to, the, 5, '\'', cap])]). relacion([sujeto(['Cap', complexes, from, proliferating, cultures, mainly, contain, 'eIF4A,', which]), verbo([associates]), complemento([with, at, least, four, cap, 'complexes,', but, eIF4A, is, replaced, by, additional, helicases, in, quiescent, cells])]). relacion([sujeto(['These', findings]), verbo([suggest]), complemento([that, the, dynamic, and, selective, recruitment, of, various, proteins, to, mRNA, 5, '\'', cap, complexes, could, play, an, important, role, in, the, regulation, of, gene, expression])]). relacion([sujeto(['The', 'cap-binding', protein, complex, '(', 'CBC)']), verbo([binds]), complemento([to, the, caps, of, all, 'RNA', polymerase, 'II', 'transcripts,', and, plays, an, important, role, in, 'RNA', metabolism])]). relacion([sujeto(['We', show, that, the, smaller, subunit, of, the, 'complex,', 'AtCBP20,', plays, a, crucial, role, in, the]), verbo([nuclear]), complemento([import, of, 'AtCBC'])]). relacion([sujeto(['The', 'C-terminal', part, of, 'AtCBP20', contains, two, functionally, independent]), verbo([nuclear]), complemento([localization, signals, '(', 'NLSs)'])]). relacion([sujeto(['At', least, one, of, these, two, 'NLSs', is]), verbo([required]), complemento([for, the, import, of, 'CBC', into, the, plant, nucleus])]). relacion([sujeto(['In', recent, years, it]), verbo([has]), complemento([become, evident, that, 'NMD', also, eliminates, a, subset, of, naturally, occurring, mRNA, during, proper, gene, expression])]). relacion([sujeto(['Additionally,', 'mammalian-cell', 'NMD', is]), verbo([promoted]), complemento([by, the, 'cap-binding', protein, heterodimer, 'CBP80/20', that, also, typifies, newly, synthesized, mRNA])]). relacion([sujeto(['Phosphorylation', appears, to]), verbo([trigger]), complemento([translational, repression, and, mRNA, decay])]). relacion([sujeto(['Although', there, are, established, rules, for, what, generally, defines, an, 'NMD']), verbo([target]), complemento([in, mammalian, 'cells,', as, with, any, rule, there, are, exceptions, 'and,', 'thus,', the, need, to, experimentally, verify, individual, mRNAs, as, bona, fide, targets, of, 'NMD'])]). relacion([sujeto(['This', chapter]), verbo([provides]), complemento([guidelines, and, protocols, for, how, to, define, 'NMD', targets, using, cultured, mammalian, cells])]). relacion([sujeto(['Here', we, characterize, a, novel, mRNP, complex, that, is]), verbo([found]), complemento([in, neuronal, dendrites, throughout, the, central, nervous, system, and, in, some, axonal, processes, of, the, spinal, cord])]). relacion([sujeto(['The', complex, is, characterized, by, the, 'LSm1', 'protein,', which, so, far]), verbo([has]), complemento([been, implicated, in, mRNA, degradation, in, nonneuronal, cells])]). relacion([sujeto(['In', 'brain,', it]), verbo([associates]), complemento([with, intact, mRNAs])]). relacion([sujeto(['Interestingly,', the, 'LSm1-mRNPs', contain, the, 'cap-binding', protein, 'CBP80', that]), verbo([associates]), complemento([with, '(', 'pre)mRNAs', in, the, 'nucleus,', suggesting, that, the, dendritic, 'LSm1', complex, has, been, assembled, in, the, nucleus])]). relacion([sujeto(['In', support, of, this, 'notion,', neuronal, 'LSm1', is, partially]), verbo([nuclear]), complemento([and, inhibition, of, mRNA, synthesis, increases, its, nuclear, localization])]). relacion([sujeto(['Importantly,', 'CBP80', is, also, present, in, the, dendrites, and, both, 'LSm1', and, 'CBP80', shift, significantly, into, the, spines, upon, stimulation, of, glutamergic, 'receptors,']), verbo([suggesting]), complemento([that, these, mRNPs, are, translationally, activated, and, contribute, to, the, regulated, local, protein, synthesis])]). relacion([sujeto(['In', this, study, we, investigated, whether, in, 'plants,', like, in, 'mammals,', components, of, the]), verbo([nuclear]), complemento(['cap-binding', protein, complex, '(', 'CBC)', are, involved, in, 'nonsense-mediated', mRNA, decay, '(', 'NMD)'])]). relacion([sujeto(['Our', results]), verbo([suggest]), complemento([that, neither, 'CBP20', nor, 'CBP80', is, involved, in, 'NMD', in, 'A'])]). relacion([sujeto(['MicroRNAs', '(', 'miRNAs)', are, 21, nt, 'RNAs', that]), verbo([regulate]), complemento([many, biological, processes, in, plants, by, mediating, translational, inhibition, or, cleavage, of, target, transcripts])]). relacion([sujeto(['Arabidopsis', mutants, defective, in, miRNA, biogenesis]), verbo([have]), complemento([overlapping, and, highly, pleiotropic, phenotypes, including, serrated, leaves, and, 'ABA', hypersensitivity])]). relacion([sujeto(['Recent', evidence, indicates, that, miRNA, genes, are]), verbo([transcribed]), complemento([by, 'RNA', polymerase, 'II', '(', 'Pol', 'II)'])]). relacion([sujeto(['Since', 'Pol', 'II', transcripts, are, 'capped,', we, hypothesized, that, 'CBP', '(', 'cap-binding', 'protein)', 20, and, 80, may]), verbo([bind]), complemento([to, capped, primary, miRNA, '(', 'pri-miRNA)', transcripts, and, play, a, role, in, their, processing])]). relacion([sujeto(['Here,', we, show, that, cbp20, and, cbp80, mutants]), verbo([have]), complemento([reduced, miRNA, levels, and, increased, 'pri-miRNA', levels])]). relacion([sujeto(['Co-immunoprecipitation', experiments, revealed, that, 'pri-miRNAs', 159, ',', 166, ',', 168, and, 172, could, be]), verbo([associated]), complemento([with, 'CBP20', and, 'CBP80'])]). relacion([sujeto(['We']), verbo([found]), complemento([that, 'CBP20', and, 'CBP80', are, stabilized, by, 'ABA', by, a, 'post-translational', 'mechanism,', and, these, proteins, are, needed, for, 'ABA', induction, of, miR159, during, seed, germination])]). relacion([sujeto(['The', lack, of, miR159, accumulation, in, 'ABA-treated', seeds, of, 'cbp20/80', mutants]), verbo([leads]), complemento([to, increased, 'MYB33', and, 'MYB101', transcript, 'levels,', and, presumably, higher, levels, of, these, positive, regulators, result, in, 'ABA', hypersensitivity])]). relacion([sujeto(['Genetic', and, molecular, analyses, show, that, 'CBP20', and, 80]), verbo([have]), complemento([overlapping, function, in, the, same, developmental, pathway, as, 'SE', and, 'HYL1'])]). relacion([sujeto(['While', early, steps, of, gene, 'expression,', such, as, transcription, 'preinitiation,', are, known, to, often, be, rate, limiting, and, to, be]), verbo([regulated]), complemento([by, such, stimuli, as, steroid, 'hormones,', the, potential, impact, of, downstream, 'steps,', including, 'splicing,', on, the, mRNA, production, rate, is, unknown])]). relacion([sujeto(['In', this, 'work,', we, studied, the, effects, of, the, transcriptional, stimulus, estradiol, on, cyclin, 'D1,', 'PS2,', and, 'c-fos', gene, expression, by, measuring, the, levels, of, 'RNA', polymerase, 'II', on, the, 'DNA', 'templates,', the, levels, of, nascent, transcripts]), verbo([associated]), complemento([with, 'RNA', polymerase, 'II,', and, the, levels, of, 'unspliced,', partially, 'spliced,', and, fully, spliced, 'RNAs'])]). relacion([sujeto(['The', mechanism]), verbo([involved]), complemento([in, cotranscriptional, splicing, depended, on, the, level, of, serine, 5, phosphorylation, of, 'RNA', polymerase, 'II', at, the, gene, 5, '\'', end, and, on, the, recruitment, of, 'CBP80,', one, of, the, two, subunits, of, the, cap, binding, 'complex,', which, stimulates, splicing, of, the, 'promoter-proximal', intron])]). relacion([sujeto(['The', plant, hormone, abscisic, acid, '(', 'ABA)', intricately]), verbo([regulates]), complemento([a, multitude, of, processes, during, plant, growth, and, development])]). relacion([sujeto(['Recent', studies]), verbo([have]), complemento([established, a, connection, between, genes, participating, in, various, steps, of, cellular, 'RNA', metabolism, and, the, 'ABA', signal, transduction, machinery])]). relacion([sujeto(['In', this, chapter, we, focus, on, the, plant]), verbo([nuclear]), complemento([mRNA, cap, binding, 'proteins,', 'CBP20', and, 'CBP80'])]). relacion([sujeto(['We', summarize, and]), verbo([report]), complemento([recent, findings, on, their, effects, on, cellular, signal, transduction, networks, and, mRNA, processing, events])]). relacion([sujeto(['Furthermore,', new, experiments, analyzing, complementation, of, cpb20, with, 'site-directed', cpb20, mutants]), verbo([provide]), complemento([evidence, that, the, 'CAP', binding, activity, of, 'CBP20', is, essential, for, the, observed, 'cbp-associated', phenotypes])]). relacion([sujeto(['In', 'conclusion,', mutants, in, genes]), verbo([participating]), complemento([in, 'RNA', processing, provide, excellent, tools, to, uncover, novel, molecular, mechanisms, for, the, regulation, of, 'RNA', metabolism, and, of, signal, transduction, networks, in, 'wild-type', plants])]). relacion([sujeto(['The', processing, of, 'Arabidopsis', thaliana, microRNAs, '(', 'miRNAs)', from, longer, primary, transcripts, '(', 'pri-miRNAs)']), verbo([requires]), complemento([the, activity, of, several, 'proteins,', including, 'DICER-LIKE1', '(', 'DCL1),', the, 'double-stranded', 'RNA-binding', protein, 'HYPONASTIC', 'LEAVES1', '(', 'HYL1),', and, the, zinc, finger, protein, 'SERRATE', '(', 'SE)'])]). relacion([sujeto(['It']), verbo([has]), complemento([been, noted, before, that, the, morphological, appearance, of, weak, se, mutants, is, reminiscent, of, plants, with, mutations, in, 'ABH1/CBP80', and, 'CBP20,', which, encode, the, two, subunits, of, the, nuclear, 'cap-binding', complex])]). relacion([sujeto(['We']), verbo([report]), complemento(['that,', like, 'SE,', the, 'cap-binding', complex, is, necessary, for, proper, processing, of, 'pri-miRNAs'])]). relacion([sujeto(['Inactivation', of, either, 'ABH1/CBP80', or, 'CBP20', results, in]), verbo([decreased]), complemento([levels, of, mature, miRNAs, accompanied, by, apparent, stabilization, of, 'pri-miRNAs'])]). relacion([sujeto(['Whole-genome', tiling, array, analyses]), verbo([reveal]), complemento([that, 'se,', 'abh1/cbp80,', and, cbp20, mutants, also, share, similar, splicing, 'defects,', leading, to, the, accumulation, of, many, partially, spliced, transcripts])]). relacion([sujeto(['This', is, unlikely, to, be, an, indirect, consequence, of, improper, miRNA, processing, or, other, mRNA, turnover, 'pathways,', because, introns]), verbo([retained]), complemento([in, 'se,', 'abh1/cbp80,', and, cbp20, mutants, are, not, affected, by, mutations, in, other, genes, required, for, miRNA, processing, or, for, 'nonsense-mediated', mRNA, decay])]). relacion([sujeto(['Here,', we, show, that, concomitant]), verbo([loss]), complemento([of, 'XRN4/EIN5,', a, 5, '\'', -, 3, '\'', 'exoribonuclease,', and, 'ABH1/CBP80,', a, subunit, of, the, mRNA, cap, binding, 'complex,', results, in, 'Arabidopsis', plants, manifesting, myriad, developmental, defects])]). relacion([sujeto(['We']), verbo([find]), complemento([that, 'ABH1/CBP80', is, necessary, to, obtain, proper, mature, miRNA, 'levels,', which, suggests, this, protein, affects, the, 'miRNA-mediated', 'RNA', silencing, pathway])]). relacion([sujeto(['We']), verbo([find]), complemento([that, the, parent, transcripts, of, these, smRNAs, accumulate, in, an, uncapped, form, upon, loss, of, 'XRN4/EIN5,', which, suggests, that, uncapped, endogenous, transcripts, can, become, smRNA, biogenesis, substrates])]). relacion([sujeto(['Overall,', our, results]), verbo([reveal]), complemento([unexpected, connections, between, 'RNA', metabolism, and, silencing, pathways])]). relacion([sujeto(['NMD', in, mammalian, cells]), verbo([targets]), complemento([newly, spliced, mRNA, that, is, bound, by, the, 'cap-binding', protein, heterodimer, 'CBP80/20', and, one, or, more, 'post-splicing', exon, junction, complexes, during, a, pioneer, round, of, translation])]). relacion([sujeto(['NMD']), verbo([targets]), complemento([mRNA, that, initiates, translation, using, the, encephalomyocarditis, virus, '(', 'EMCV)', internal, ribosome, entry, site, '(', 'IRES),', therefore, 'NMD', might, target, not, only, 'CBP80/20-bound', mRNA, but, also, its, remodelled, 'product,', 'eIF4E-bound', mRNA])]). relacion([sujeto(['Here,', we]), verbo([provide]), complemento([evidence, that, 'NMD', triggered, by, translation, initiation, at, the, 'EMCV', 'IRES,', similar, to, 'NMD', triggered, by, translation, initiation, at, an, mRNA, 'cap,', targets, 'CBP80/20-bound', mRNA, but, does, not, detectably, target, 'eIF4E-bound', mRNA])]). relacion([sujeto(['NMD']), verbo([targets]), complemento([newly, synthesized, mRNAs, bound, by, nuclear, 'cap-binding', proteins, 80, /, 20, '(', 'CBP80/20)', and, exon, junction, complex, '(', 'EJC),', the, former, of, which, is, thought, to, recruit, the, ribosome, to, initiate, the, pioneer, round, of, translation])]). relacion([sujeto(['After', completion, of, the, pioneer, round, of, 'translation,', 'CBP80/20', is, replaced, by, the, cytoplasmic, 'cap-binding', protein, 'eIF4E,', which]), verbo([mediates]), complemento(['steady-state', translation, in, the, cytoplasm])]). relacion([sujeto(['Here,', we, show, that, overexpression, of, 'eIF4E-T', preferentially]), verbo([inhibits]), complemento(['cap-dependent', 'steady-state', 'translation,', but, not, the, pioneer, round, of, translation])]). relacion([sujeto(['We', also, demonstrate, that, overexpression, of, 'eIF4E-T', or, 'Dcp1a']), verbo([triggers]), complemento([the, movement, of, eIF4E, into, the, processing, bodies])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, the, pioneer, round, of, translation, differs, from, 'steady-state', translation, in, terms, of, ribosome, recruitment])]). relacion([sujeto(['NMD']), verbo([targets]), complemento([only, mRNAs, bound, by, the, nuclear, 'cap-binding', protein, complex, 'CBP80/20', which, directs, the, pioneer, round, of, translation])]). relacion([sujeto(['Nonsense-mediated', mRNA, decay, '(', 'NMD)', generally, eliminates, messenger, 'RNAs', that, prematurely, terminate, translation, and, occurs, in, all, eukaryotes, that]), verbo([have]), complemento([been, 'studied,', although, with, mechanistic, variations])]). relacion([sujeto(['In', 'mammals,', 'NMD', seems, to, be, restricted, to, newly, synthesized, mRNA, that, is]), verbo([bound]), complemento([by, the, 'cap-binding', heterodimer, 'CBP80-CBP20', '(', 'CBP80/20)', and, typically, has, at, least, one, exon, junction, complex, '(', 'EJC)', situated, downstream, of, the, nonsense, codon, and, added, 'post-splicing'])]). relacion([sujeto(['However,', mammalian, 'NMD', can, also]), verbo([target]), complemento([spliced, mRNA, lacking, an, 'EJC', downstream, of, the, nonsense, codon])]). relacion([sujeto(['Here', we]), verbo([provide]), complemento([evidence, that, this, additional, 'pathway,', known, as, failsafe, 'NMD,', likewise, seems, to, be, restricted, to, 'CBP80/20-bound', mRNA, and, does, not, detectably, target, its, subsequently, remodeled, 'product,', 'eIF4E-bound', mRNA])]). relacion([sujeto(['Our', 'studies,', including, analyses, of, factor, 'dependence,']), verbo([reveal]), complemento([important, shared, features, of, the, two, 'mammalian-cell', 'NMD', pathways, as, well, as, fundamental, differences, between, 'NMD', in, mammals, and, 'Saccharomyces', cerevisiae])]). relacion([sujeto(['Nuclear', 'cap-binding', protein, complex, 'CBP80/20']), verbo([binds]), complemento([to, those, mRNAs, at, the, 5, '\'', -, 'end,', recruiting, translation, initiation, complex])]). relacion([sujeto(['As', a, consequence, of, the, pioneer, round, of, 'translation,', the]), verbo([bound]), complemento(['EJCs', are, dissociated, from, mRNAs, and, 'CBP80/20', is, replaced, by, the, cytoplasmic, 'cap-binding', protein, eIF4E])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, mRNAs, enter, the, pioneer, round, of, translation, during, serum, starvation, and, are, targeted, for, 'NMD', if, they, contain, premature, termination, codons])]). relacion([sujeto(['We', previously]), verbo([reported]), complemento([that, inhibition, of, polyadenylation, at, '(', 'pA)p,', necessary, for, 'read-through', of, 'P41-generated', capsid, gene, 'pre-mRNAs', which, are, subsequently, 'spliced,', requires, binding, of, 'U1', snRNP, to, the, upstream, donor])]). relacion([sujeto(['Inhibition', was, reduced, as, the, distance, between, the, cap, site, and, the, donor, was]), verbo([increased]), complemento(['(', increasing, the, size, of, the, 5, '\'', 'exon)'])]). relacion([sujeto(['Here,', we]), verbo([have]), complemento([demonstrated, that, 'U1-70K', is, a, key, component, of, 'U1', snRNP, that, mediates, inhibition, of, polyadenylation, at, '(', 'pA)p'])]). relacion([sujeto(['Furthermore,', introduction, of, a, 'U-rich', 'stretch,', predicted, to]), verbo([target]), complemento(['TIA-1', and, thus, increase, the, affinity, of, 'U1', snRNP, binding, to, the, intervening, donor, 'site,', significantly, augmented, inhibition, of, '(', 'pA)p,', while, depletion, of, 'TIA-1', by, siRNA, increased, '(', 'pA)p', 'read-through'])]). relacion([sujeto(['Finally,', artificially, tethering, the, cap]), verbo([binding]), complemento([complex, '(', 'CBC)', components, 'CBP80', and, 'CBP20', upstream, of, the, intron, donor, increased, inhibition, of, polyadenylation, at, '(', 'pA)p'])]). relacion([sujeto(['Our', results]), verbo([suggest]), complemento([that, interaction, with, the, 'CBC', strengthens, 'U1', snRNP, binding, to, the, downstream, intron, donor, in, a, manner, inversely, proportional, to, the, size, of, the, 5, '\'', 'exon,', thus, governing, the, competition, between, intron, splicing, and, polyadenylation, at, '(', 'pA)p'])]). relacion([sujeto(['This', competition, must, be, optimized, to, program, both, the, levels, of, polyadenylation, of, 'P7-', and, 'P19-generated', 'RNA', at, '(', 'pA)p']), verbo([required]), complemento([to, produce, proper, levels, of, the, essential, 'Rep', proteins, and, the, splicing, of, 'P41-generated', 'RNAs', to, produce, the, proper, ratio, of, capsid, proteins, during, 'AAV5', infection])]). relacion([sujeto(['The', mammalian, integration, site, 6, '(', 'INT6)', protein]), verbo([has]), complemento([been, implicated, in, breast, carcinogenesis, and, characterized, as, the, eIF3e, 'non-core', subunit, of, the, translation, initiation, factor, 'eIF3,', but, its, role, in, this, complex, is, not, known])]). relacion([sujeto(['Here,', we, show, that, 'INT6', knockdown, by, 'RNA', interference, strongly]), verbo([inhibits]), complemento(['nonsense-mediated', messenger, 'RNA', decay, '(', 'NMD),', which, triggers, degradation, of, mRNAs, with, premature, stop, codons])]). relacion([sujeto(['In', contrast, to, the, eIF3b, core, 'subunit,', which, is]), verbo([required]), complemento([for, both, 'NMD', and, general, 'translation,', 'INT6', is, only, necessary, for, the, former, process])]). relacion([sujeto(['In', 'addition,', several, transcripts, known, to, be, upregulated, by, 'UPF1', or, 'UPF2', depletion, were, also]), verbo([found]), complemento([to, be, sensitive, to, 'INT6', suppression])]). relacion([sujeto(['From', these, 'observations,', we, propose, that, 'INT6,', in, association, with, 'eIF3,', is]), verbo([involved]), complemento([in, routing, specific, mRNAs, for, degradation])]). relacion([sujeto(['Insulin-like', growth, factor, 'II', 'mRNA-binding', protein, '(', 'IMP)', zip, 'code-binding', proteins]), verbo([participate]), complemento([in, mRNA, 'localization,', and, in, motile, cells, 'IMP-containing', granules, are, dispersed, around, the, nucleus, and, in, cellular, protrusions])]). relacion([sujeto(['We', isolated, the, 'IMP1-containing', 'RNP', granules, and]), verbo([found]), complemento([that, they, represent, a, unique, 'RNP', entity, distinct, from, neuronal, hStaufen, 'and/or', fragile, 'X', mental, retardation, protein, 'granules,', processing, 'bodies,', and, stress, granules])]). relacion([sujeto(['Granules', were, 100, -, 300, nm, in, diameter, and, consisted, of, 'IMPs,', 40, 'S', ribosomal, 'subunits,', shuttling, heterologous]), verbo([nuclear]), complemento(['RNPs,', 'poly(A)-binding', 'proteins,', and, mRNAs])]). relacion([sujeto(['Messenger', 'RNAs', encoding, proteins]), verbo([participating]), complemento([in, the, secretory, pathway, and, endoplasmic, 'reticulum-associated', quality, 'control,', as, well, as, 'ubiquitin-dependent', 'metabolism,', were, enriched, in, the, 'granules,', reinforcing, the, concept, of, 'RNP', granules, as, 'post-transcriptional', operons])]). relacion([sujeto(['Here', we, investigated, the, mechanism, for, recruitment, of, the]), verbo([conserved]), complemento([mRNA, export, machinery, '(', 'TREX', 'complex)', to, mRNA])]). relacion([sujeto(['We', show, that, the, human, 'TREX', complex, is]), verbo([recruited]), complemento([to, a, region, near, the, 5, '\'', end, of, 'mRNA,', with, the, 'TREX', component, 'Aly', bound, closest, to, the, 5, '\'', cap])]). relacion([sujeto(['Both', 'TREX', recruitment, and, mRNA, export]), verbo([require]), complemento([the, 'cap,', and, these, roles, for, the, cap, are, splicing, dependent])]). relacion([sujeto(['CBP80,', which, is]), verbo([bound]), complemento([to, the, 'cap,', associates, efficiently, with, 'TREX,', and, 'Aly', mediates, this, interaction])]). relacion([sujeto(['As', a, 'consequence,', the, mRNA, would, be, exported, in, a, 5, '\'', to, 3, '\'', direction, through, the]), verbo([nuclear]), complemento(['pore,', as, observed, in, early, electron, micrographs, of, giant, 'Balbiani', ring, mRNPs])]). relacion([sujeto(['Here', we]), verbo([have]), complemento([investigated, how, the, cap, binding, complex, '(', 'CBC)', affects, human, 'PARN', activity])]). relacion([sujeto(['We', showed, that, 'CBC,', via, its, 80, -, kDa, subunit, '(', 'CBP80),']), verbo([inhibited]), complemento(['PARN,', suggesting, that, 'CBC', can, regulate, mRNA, deadenylation])]). relacion([sujeto(['The', 'CBC-mediated', inhibition, of, 'PARN', was, 'cap-independent,', and, in, keeping, with, 'this,', the, 'CBP80', subunit, alone]), verbo([inhibited]), complemento(['PARN'])]). relacion([sujeto(['Our', data]), verbo([suggested]), complemento([a, new, function, for, 'CBC,', identified, 'CBC', as, a, potential, regulator, of, 'PARN,', and, emphasized, the, importance, of, communication, between, the, two, extreme, ends, of, the, mRNA, as, a, key, strategy, to, regulate, mRNA, degradation])]). relacion([sujeto(['Based', on, our, 'data,', we]), verbo([have]), complemento([proposed, a, model, for, 'CBC-mediated', regulation, of, 'PARN,', which, relies, on, an, interaction, between, 'CBP80', and, 'PARN'])]). relacion([sujeto(['Association', of, 'CBC', with, 'PARN', might]), verbo([have]), complemento([importance, in, the, regulated, recruitment, of, 'PARN', to, the, 'nonsense-mediated', decay, pathway, during, the, pioneer, round, of, translation])]). relacion([sujeto(['In', mammalian, 'cells,', 'nonsense-mediated', messenger, 'RNA', decay, '(', 'NMD)']), verbo([targets]), complemento([newly, synthesized, 'nonsense-containing', mRNA, bound, by, the, 'cap-binding-protein', heterodimer, 'CBP80-CBP20', and, at, least, one, 'exon-junction', complex, '(', 'EJC)'])]). relacion([sujeto(['An', 'EJC', includes, the, 'NMD', factors, 'Upf3', or, 'Upf3X', and, 'Upf2,', and, 'Upf2']), verbo([recruits]), complemento(['Upf1'])]). relacion([sujeto(['Once', this, pioneer, translation, initiation, complex, is, remodeled, so, that, 'CBP80-CBP20', is, replaced, by, eukaryotic, initiation, factor, '4E,', the, mRNA, is, no, longer, detectably]), verbo([targeted]), complemento([for, 'NMD'])]). relacion([sujeto(['Here,', we]), verbo([provide]), complemento([evidence, that, 'CBP80', augments, the, efficiency, of, 'NMD', but, not, of, 'Staufen1', '(', 'Stau1)-mediated', mRNA, decay, '(', 'SMD)'])]). relacion([sujeto(['We']), verbo([find]), complemento([that, 'CBP80', interacts, with, 'Upf1', and, promotes, the, interaction, of, 'Upf1', with, 'Upf2', but, not, with, 'Stau1'])]). relacion([sujeto(['Together', with, the, 'cap-binding', protein, 'eIF4E,', it]), verbo([recruits]), complemento([the, small, ribosomal, subunit, to, the, 5, '\'', -, end, of, mRNA, and, promotes, the, assembly, of, a, functional, translation, initiation, 'complex,', which, scans, along, the, mRNA, to, the, translation, start, codon])]). relacion([sujeto(['Human', eIF4G, contains, three, consecutive, 'HEAT', 'domains,', as, well, as, long, unstructured, regions]), verbo([involved]), complemento([in, multiple, 'protein-protein', interactions])]). relacion([sujeto(['Despite', the, accumulating, data, about, the, structure, and, function, of, 'eIF4G,', the, mechanisms, of, coordination, and, regulation, of, its, interactions, with, other, factors]), verbo([have]), complemento([remained, largely, unknown])]). relacion([sujeto(['Here,', we, present, evidence, that, eIF4G, and, the, large, subunit, of, the]), verbo([nuclear]), complemento(['cap-binding', 'complex,', 'CBP80,', share, a, common, origin, and, domain, structure])]). relacion([sujeto(['The', structure, of, 'CBP80,', in, complex, with, the]), verbo([nuclear]), complemento(['cap-binding', protein, 'CBP20,', is, used, to, build, a, model, for, the, mutual, orientation, of, the, domains, in, eIF4G, and, their, interactions, with, other, factors])]). relacion([sujeto(['The', organization, of, the, 'CBP80-CBP20', complex]), verbo([suggests]), complemento([how, the, activity, of, eIF4G, in, translation, initiation, could, be, regulated, through, a, dynamic, network, of, overlapping, 'intra-', and, intermolecular, interactions, centered, around, the, eIF4G, 'HEAT', domains])]). relacion([sujeto(['Nonsense-mediated', mRNA, decay, '(', 'NMD)', in, mammalian, cells]), verbo([targets]), complemento(['cap-binding', protein, 80, '(', 'CBP80)-bound', mRNA, during, or, after, a, pioneer, round, of, translation])]). relacion([sujeto(['We', show, that, 'baculovirus-produced', 'CBP80', and, 'CBP20', independently]), verbo([interact]), complemento([with, eIF4GI])]). relacion([sujeto(['The', interactions, between, eIF4G, and, the, heterodimer, 'CBP80/20']), verbo([suggest]), complemento([that, eIF4G, has, a, function, in, the, pioneer, initiation, complex, rather, than, merely, a, presence, during, remodeling, to, the, 'steady-state', complex])]). relacion([sujeto(['First,', 'NMD', is]), verbo([inhibited]), complemento([upon, eIF4G, cleavage, by, 'HIV-2', or, poliovirus, 2, 'A', protease])]). relacion([sujeto(['Second,', eIF4GI, coimmunopurifies, with, 'pre-mRNA,', indicating, that, it]), verbo([associates]), complemento([with, transcripts, before, the, pioneer, round])]). relacion([sujeto(['However,', recent, studies, of, 'nonsense-mediated', mRNA, decay, '(', 'NMD)', indicate, that, 'cap-binding', protein, '(', 'CBP)80-bound', 'mRNA,', which, is, a, precursor, to, 'eIF4E-bound', 'mRNA,', can, also, be]), verbo([translated]), complemento([during, a, pioneer, round, of, translation])]). relacion([sujeto(['Here,', we]), verbo([report]), complemento([that, the, pioneer, 'round,', which, can, be, assessed, by, measuring, 'NMD,', is, not, inhibited, by, '4E-BP1,', which, is, known, to, inhibit, 'steady-state', translation, by, competing, with, eIF4G, for, binding, to, eIF4E])]). relacion([sujeto(['eIF4GI,', 'poly(A)-binding', protein, '(', 'PABP)1,', 'eIF3,', 'eIF4AI,', and, eIF2alpha, coimmunopurify, with, both, 'CBP80', and, 'eIF4E,', which]), verbo([suggests]), complemento([that, each, factor, functions, in, both, modes, of, translation])]). relacion([sujeto(['Consistent', with, roles, for, 'PABP1', and, eIF2alpha, in, the, pioneer, round, of, 'translation,', 'PABP-interacting', protein, 2, ',', which, is, known, to, destabilize, 'PABP1']), verbo([binding]), complemento([to, 'poly(A)', and, inhibit, 'steady-state', 'translation,', as, well, as, inactive, 'eIF2alpha,', which, is, also, known, to, inhibit, 'steady-state', 'translation,', also, inhibit, 'NMD'])]). relacion([sujeto(['Polysome', profiles, indicate, that, 'CBP80-bound', mRNAs, are]), verbo([translated]), complemento([less, efficiently, than, their, 'eIF4E-bound', counterparts])]). relacion([sujeto(['Studies', of, 'nonsense-mediated', mRNA, decay, in, mammalian, cells]), verbo([have]), complemento([proffered, unforeseen, insights, into, changes, in, 'mRNA-protein', interactions, throughout, the, lifetime, of, an, mRNA])]). relacion([sujeto(['Complex-loaded', mRNA, is, thought, to, undergo, a, pioneer, round, of, translation, when, still]), verbo([bound]), complemento([by, 'cap-binding', proteins, 'CBP80', and, 'CBP20', and, 'poly(A)-binding', protein, 2])]). relacion([sujeto(['The', acquisition, and]), verbo([loss]), complemento([of, 'mRNA-associated', proteins, accompanies, the, transition, from, the, pioneer, round, to, subsequent, rounds, of, 'translation,', and, from, translational, competence, to, substrate, for, 'nonsense-mediated', mRNA, decay])]). relacion([sujeto(['Processing', of]), verbo([nuclear]), complemento(['pre-mRNA', is, an, important, step, in, the, regulation, of, gene, expression, and, involves, 5, '(', '\'', ')', -, and, 3, '(', '\'', ')', -, end, 'processing,', 'splicing,', and, editing])]). relacion([sujeto(['Mammalian']), verbo([nuclear]), complemento(['pre-mRNAs', are, assembled, in, large, ribonucleoprotein, '(', 'lnRNP)', 'complexes,', in, which, the, entire, population, of, nuclear, 'pre-mRNA', is, individually, packaged, until, it, is, exported, to, the, cytoplasm])]). relacion([sujeto(['They', are, composed, of, four, spliceosomal, substructures, and, an, additional, 'one,', which, are, interconnected, by, the, 'pre-mRNA,', and]), verbo([have]), complemento([an, overall, mass, of, 21, 'MDa'])]). relacion([sujeto(['The', additional, substructure, was, proposed, to, harbor, additional, processing, 'activities,', such, as, editing, components, that, were, shown, to, be]), verbo([associated]), complemento([with, the, lnRNP, particles])]). relacion([sujeto(['Here', we, show, that, the, 'cap-binding', proteins, '(', 'CBPs),', 'CBP20', and, 'CBP80,', are]), verbo([associated]), complemento([with, the, lnRNP, 'particles,', as, well, as, components, of, the, 3, '(', '\'', ')', -, 'end-processing', activity])]). relacion([sujeto(['These', 'results,', together, with, our, previous, demonstration, of, the, association, of, splicing, factors, and, 'A-to-I', editing, enzymes, with, lnRNP, 'particles,', support, the, view, that, the, lnRNP, particles, are, the]), verbo([nuclear]), complemento(['pre-mRNA', processing, machine])]). relacion([sujeto(['Such', a, machine, is]), verbo([required]), complemento([to, execute, the, nuclear, processing, steps, of, the, 'pre-mRNA', in, an, accurate, and, regulated, manner])]). relacion([sujeto(['The', supraspliceosomal, 'pre-mRNA', processing, 'machine,', in, which, each, substructure, represents, a, functional, 'spliceosome,']), verbo([provides]), complemento([a, frame, onto, which, the, 'pre-mRNA', is, folded])]). relacion([sujeto(['This', model, can, account, for]), verbo([regulated]), complemento([alternative, 'splicing,', which, is, a, major, source, of, protein, versatility, in, mammals])]). relacion([sujeto(['The']), verbo([nuclear]), complemento(['cap-binding', complex, '(', 'CBC)', binds, the, 7, -, 'methyl-G(5\')ppp(5\')N', cap, structure, at, the, 5, '\'', end, of, 'pre-messenger', and, 'uracil-rich', small, nuclear, 'RNAs', in, the, nucleus])]). relacion([sujeto(['It']), verbo([mediates]), complemento([interaction, of, these, capped, 'RNAs', with, various, nuclear, machineries, involved, in, 'RNA', maturation, and, is, 'co-exported', with, them, to, the, cytoplasm])]). relacion([sujeto(['The', structure, of, human, 'CBC,', which, comprises, the, subunits, 'CBP20', and, 'CBP80,']), verbo([has]), complemento([previously, been, determined, in, a, mildly, trypsinated, form, which, can, no, longer, bind, the, cap])]). relacion([sujeto(['Two', 'cap-binding', proteins]), verbo([mediate]), complemento([these, 'effects:', cytosolic, 'eIF-4E', and, nuclear, 'cap-binding', protein, complex, '(', 'CBC)'])]). relacion([sujeto(['The', latter, consists, of, a, 'CBP20', 'subunit,', which]), verbo([binds]), complemento([the, 'cap,', and, a, 'CBP80', 'subunit,', which, ensures, 'high-affinity', cap, binding])]). relacion([sujeto(['Here', we]), verbo([report]), complemento([the, 2.1, 'A', resolution, structure, of, human, 'CBC', with, the, cap, analog, 'm7GpppG,', as, well, as, the, structure, of, unliganded, 'CBC'])]). relacion([sujeto(['Comparisons', between, these, structures, indicate, that, the, cap]), verbo([induces]), complemento([substantial, conformational, changes, within, the, 'N-terminal', loop, of, 'CBP20,', enabling, 'Tyr', 20, to, join, 'Tyr', 43, in, 'pi-pi', stacking, interactions, with, the, methylated, guanosine, base])]). relacion([sujeto(['The', structure, for, the, 'CBC']), verbo([bound]), complemento([to, m7GpppG, highlights, interesting, similarities, and, differences, between, 'CBC', and, 'eIF-4E,', and, provides, insights, into, the, regulatory, mechanisms, used, by, growth, factors, and, other, extracellular, stimuli, to, influence, the, 'cap-binding', state, of, the, 'CBC'])]). relacion([sujeto(['The', heterodimeric]), verbo([nuclear]), complemento(['cap-binding', complex, '(', 'CBC)', binds, to, the, 5, '\'', cap, structure, of, 'RNAs', in, the, nucleus, and, plays, a, central, role, in, their, diverse, maturation, steps])]). relacion([sujeto(['We', describe, the, crystal, structure, at, 2.1, 'A', resolution, of, human, 'CBC']), verbo([bound]), complemento([to, an, 'm(7)GpppG', cap, analogue])]). relacion([sujeto(['Comparison', with, the, structure, of, uncomplexed, 'CBC', shows, that, cap]), verbo([binding]), complemento([induces, 'co-operative', folding, around, the, dinucleotide, of, some, 50, residues, from, the, 'N-', and, 'C-terminal', extensions, to, the, central, 'RNP', domain, of, the, small, subunit, 'CBP20'])]). relacion([sujeto(['Although', the, structure, is, very, different, from, that, of, other, known, 'cap-binding', 'proteins,', such, as, the, cytoplasmic, 'cap-binding', protein, 'eIF4E,', specificity, for, the, methylated, guanosine, again, is, achieved, by, sandwiching, the, base, between, two, aromatic, 'residues,', in, this, case, two]), verbo([conserved]), complemento([tyrosines])]). relacion([sujeto(['Implications', for, the, transfer, of, capped, mRNAs, to, 'eIF4E,']), verbo([required]), complemento([for, translation, 'initiation,', are, discussed])]). relacion([sujeto(['This', complex]), verbo([recruits]), complemento(['Upf3', and, 'Upf2,', which, function, in, 'nonsense-mediated', mRNA, decay, '(', 'NMD)'])]). relacion([sujeto(['Both', 'Upf', proteins, are, detected, on, mRNA]), verbo([bound]), complemento([by, the, major, nuclear, 'cap-binding', proteins, 'CBP80/CBP20', but, not, mRNA, bound, by, the, major, cytoplasmic, 'cap-binding', protein, eIF4E])]). relacion([sujeto(['These', and, other, data, indicate, that, 'NMD']), verbo([targets]), complemento(['CBP80-bound', mRNA, during, a, '\'', 'pioneer\'', round, of, 'translation,', but, whether, nuclear, eIF4E, also, binds, nascent, but, 'dead-end', transcripts, is, unclear])]). relacion([sujeto(['Here', we]), verbo([provide]), complemento([evidence, that, nuclear, 'CBP80', but, not, nuclear, eIF4E, is, readily, detected, in, association, with, 'intron-containing', 'RNA', and, the, 'C-terminal', domain, of, 'RNA', polymerase, 'II'])]). relacion([sujeto(['Consistent', with, this, 'evidence,', we, demonstrate, that, 'RNPS1,', 'Y14,', 'SRm160,', 'REF/Aly,', 'TAP,', 'Upf3X', and, 'Upf2', are, detected, in, the]), verbo([nuclear]), complemento([fraction, on, 'CBP80-bound', but, not, 'eIF4E-bound', mRNA])]). relacion([sujeto(['In', this]), verbo([report]), complemento([we, characterize, two, 'Arabidopsis', thaliana, 'proteins,', named, 'AtCBP20', and, 'AtCBP80,', that, are, homologues, of, human, subunits, of, a, nuclear, 'cap-binding', protein, complex, '(', 'CBC)'])]). relacion([sujeto(['AtCBP20']), verbo([has]), complemento([a, calculated, molecular, mass, of, 29.9, 'kDa,', and, 'AtCBP80', is, a, 96.5, kDa, protein])]). relacion([sujeto(['Like', its, human, 'homologue,', 'AtCBP20', contains, a, canonical, 'RNA']), verbo([binding]), complemento([domain, '(', 'RBD)', with, single, 'RNP2', and, 'RNP1', motifs])]). relacion([sujeto(['In', addition, to, the, 'N-terminal', 'part,', which, is, similar, to, the, human, 'protein,', 'AtCBP20']), verbo([has]), complemento([a, long, 'C-terminus', rich, in, 'arginine,', glycine, and, aspartate, residues])]). relacion([sujeto(['This', 'domain,', described, also, in, eIF4G, and, 'NMD2', 'proteins,', is, thought, to, be]), verbo([involved]), complemento([in, 'protein-protein', and, also, in, 'protein--RNA', interactions])]). relacion([sujeto(['AtCBP20', and, 'AtCBP80', are, constitutively]), verbo([expressed]), complemento([in, all, examined, organs, of, 'A'])]). relacion([sujeto(['We', used, antibody, to, the]), verbo([nuclear]), complemento([cap, binding, protein, 'CBP80', or, its, cytoplasmic, counterpart, eIF4E, to, immunopurify, 'RNP', containing, 'nonsense-free', or, 'nonsense-containing', transcripts])]). relacion([sujeto(['These', findings]), verbo([provide]), complemento([evidence, that, translation, can, take, place, in, association, with, 'CBP80'])]). relacion([sujeto(['The', heterodimeric]), verbo([nuclear]), complemento([cap, binding, complex, '(', 'CBC)', binds, to, 5, '\'', -, capped, polymerase, 'II', transcripts])]). relacion([sujeto(['It']), verbo([enhances]), complemento([the, efficiency, of, several, mRNA, maturation, steps, and, is, essential, for, 'U', snRNA, nuclear, export, in, multicellular, eukaryotes])]). relacion([sujeto(['The', 2, 'A', crystal, structure, of, human, 'CBC', shows, that, the, large, 'subunit,', 'CBP80,', comprises, three, 'domains,', each, containing, consecutive, helical, hairpins, and, resembling, the, 'so-called', 'MIF4G', domain]), verbo([found]), complemento([in, several, other, proteins, involved, in, 'RNA', metabolism])]). relacion([sujeto(['The', small, 'subunit,', 'CPB20,']), verbo([has]), complemento([an, 'RNP', fold, and, associates, with, the, second, and, third, domains, of, 'CBP80'])]). relacion([sujeto(['A', model, for, cap]), verbo([binding]), complemento([is, proposed, based, on, these, results, and, the, known, mode, of, binding, of, 'RNA', to, 'RNP', domains])]). relacion([sujeto(['In', eukaryotes, the, majority, of, mRNAs]), verbo([have]), complemento([an, 'm(7)G', cap, that, is, added, cotranscriptionally, and, that, plays, an, important, role, in, many, aspects, of, mRNA, metabolism])]). relacion([sujeto(['The']), verbo([nuclear]), complemento(['cap-binding', complex, '(', 'CBC;', consisting, of, 'CBP20', and, 'CBP80)', mediates, the, stimulatory, functions, of, the, cap, in, 'pre-mRNA', 'splicing,', 3, '\'', end, 'formation,', and, 'U', snRNA, export])]). relacion([sujeto(['As', little, is, known, about, how]), verbo([nuclear]), complemento(['CBC', mediates, the, effects, of, the, cap, in, higher, 'eukaryotes,', we, have, characterized, proteins, that, interact, with, 'CBC', in, 'HeLa', cell, nuclear, extracts, as, potential, mediators, of, its, function])]). relacion([sujeto(['Using', 'cross-linking', and, 'coimmunoprecipitation,', we, show, that, eukaryotic, translation, initiation, factor, 4, 'G', '(', 'eIF4G),', in, addition, to, its, function, in, the, 'cytoplasm,', is, a]), verbo([nuclear]), complemento(['CBC-interacting', protein])]). relacion([sujeto(['We', demonstrate, that, eIF4G]), verbo([interacts]), complemento([with, 'CBC', in, vitro, and, 'that,', in, addition, to, its, cytoplasmic, 'localization,', there, is, a, significant, nuclear, pool, of, eIF4G, in, mammalian, cells, in, vivo])]). relacion([sujeto(['Immunoprecipitation', experiments]), verbo([suggest]), complemento(['that,', in, contrast, to, the, cytoplasmic, 'pool,', much, of, the, nuclear, eIF4G, is, not, associated, with, eIF4E, '(', translation, cap, binding, protein, of, 'eIF4F)', but, is, associated, with, 'CBC'])]). relacion([sujeto(['While', eIF4G, stably]), verbo([associates]), complemento([with, spliceosomes, in, vitro, and, shows, close, association, with, spliceosomal, snRNPs, and, splicing, factors, in, 'vivo,', depletion, studies, show, that, it, does, not, participate, directly, in, the, splicing, reaction])]). relacion([sujeto(['Taken', together, the, data, indicate, that]), verbo([nuclear]), complemento([eIF4G, may, be, recruited, to, 'pre-mRNAs', via, its, interaction, with, 'CBC', and, accompanies, the, mRNA, to, the, 'cytoplasm,', facilitating, the, switching, of, 'CBC', for, eIF4F])]). relacion([sujeto(['This', may]), verbo([provide]), complemento([a, mechanism, to, couple, nuclear, and, cytoplasmic, functions, of, the, mRNA, cap, structure])]). relacion([sujeto(['The', importance, of, the, coordination, of, different, cell, functions, by, 'Cdc42', is, underscored, by, the, fact, that, a, constitutively, active, 'Cdc42', mutant]), verbo([induces]), complemento([cellular, transformation])]). relacion([sujeto(['In', this, 'study,', we, describe, a, novel, function, for, 'Cdc42:', its, ability, to]), verbo([stimulate]), complemento(['pre-messenger', 'RNA', splicing])]). relacion([sujeto(['A', likely, candidate, protein, for]), verbo([mediating]), complemento([the, 'Cdc42', effects, on, 'pre-mRNA', splicing, is, the, nuclear, 'RNA', 'cap-binding', complex, '(', 'CBC),', which, plays, a, key, role, in, an, early, step, of, 'cap-dependent', 'RNA', splicing])]). relacion([sujeto(['Activation', of, the, 'CBC', by, 'Cdc42', can, be]), verbo([inhibited]), complemento([by, rapamycin])]). relacion([sujeto(['Additionally,', phosphatidylinositol, 3, -, kinase, and, the, 'Cdc42', 'effector,', pp70, 'S6', 'kinase,']), verbo([stimulate]), complemento([the, 'RNA', 'cap-binding', activity, of, the, 'CBC'])]). relacion([sujeto(['S6', kinase, may, directly]), verbo([target]), complemento([the, 'CBC', in, vivo, as, it, can, phosphorylate, the, 80, -, kDa, subunit, of, the, 'CBC,', 'CBP80,', at, residues, that, are, subject, to, a, growth, 'factor-dependent', and, 'rapamycin-sensitive', phosphorylation, in, vivo])]). relacion([sujeto(['Together', these, data]), verbo([suggest]), complemento([the, involvement, of, a, 'Cdc42-S6', kinase, pathway, in, the, regulation, of, 'RNA', 'splicing,', mediated, by, an, increase, in, capped, 'RNA', binding, by, the, 'CBC,', as, well, as, raise, the, possibility, that, the, effects, of, 'Cdc42', on, cell, growth, may, be, due, in, part, to, its, regulation, of, 'RNA', processing])]). relacion([sujeto(['Computational', analysis, of, sequences, of, proteins]), verbo([involved]), complemento([in, translation, initiation, in, eukaryotes, reveals, a, number, of, specific, domains, that, are, not, represented, in, bacteria, or, archaea])]). relacion([sujeto(['Most', of, these, 'eukaryote-specific', domains, are, known, or, predicted, to, possess, an, 'alpha-helical', 'structure,', which]), verbo([suggests]), complemento([that, such, domains, are, easier, to, invent, in, the, course, of, evolution, than, are, domains, of, other, structural, classes])]). relacion([sujeto(['A', previously, 'undetected,']), verbo([conserved]), complemento([region, predicted, to, form, an, 'alpha-helical', domain, is, delineated, in, the, initiation, factor, 'eIF4G,', in, 'Nonsense-mediated', mRNA, decay, 2, protein, '(', 'NMD2/UPF2),', in, the, nuclear, 'cap-binding', 'CBP80,', and, in, 'other,', poorly, characterized, 'proteins,', which, is, named, the, 'NIC', '(', 'NMD2,', 'eIF4G,', 'CBP80)', domain])]). relacion([sujeto(['It', is, demonstrated, 'that,', in, the, course, of, eukaryotic, 'evolution,', initiation, factor, 'eIF4G,', of, which, 'NIC', is, the, 'core,']), verbo([conserved]), complemento(['portion,', has, accreted, several, 'additional,', distinct, predicted, domains, such, as, 'MI', '(', 'MA-3', and, eIF4G, ')', and, 'W2,', which, probably, was, accompanied, by, acquisition, of, new, regulatory, interactions])]). relacion([sujeto(['A', number, of, 'RNA-binding', proteins, are]), verbo([associated]), complemento([with, mRNAs, in, both, the, nucleus, and, the, cytoplasm])]). relacion([sujeto(['One', of, 'these,', 'Npl3p,', is, a, heterogeneous]), verbo([nuclear]), complemento(['ribonucleoprotein-like', protein, with, some, similarity, to, 'SR', proteins, and, is, essential, for, growth, in, the, yeast, 'S'])]). relacion([sujeto(['Temperature-sensitive', alleles]), verbo([have]), complemento([defects, in, the, export, of, mRNA, out, of, the, nucleus, '(', 1, ')'])]). relacion([sujeto(['The', 'cyc1-512', mutation, in, 'Saccharomyces', cerevisiae]), verbo([causes]), complemento([a, 90, '%', reduction, in, the, level, of, 'iso-1-cytochrome', c, because, of, the, lack, of, a, proper, 3, '\'', -, 'end-forming', 'signal,', resulting, in, low, levels, of, eight, aberrantly, long, 'cyc1-512', mRNAs, which, differ, in, length, at, their, 3, '\'', termini])]). relacion([sujeto(['cyc1-512', can, be]), verbo([suppressed]), complemento([by, deletion, of, either, of, the, nonessential, genes, 'CBC1', and, 'CBC2,', which, encode, the, 'CBP80', and, 'CBP20', subunits, of, the, nuclear, cap, binding, 'complex,', 'respectively,', or, by, deletion, of, the, nonessential, gene, 'UPF1,', which, encodes, a, major, component, of, the, mRNA, surveillance, complex])]). relacion([sujeto(['The', 'upf1-Delta', deletion]), verbo([suppressed]), complemento([the, 'cyc1-512', defect, by, diminishing, degradation, of, the, longer, subset, of, 'cyc1-512', 'mRNAs,', suggesting, that, downstream, elements, or, structures, occurred, in, the, extended, 3, '\'', 'region,', similar, to, the, downstream, elements, exposed, by, transcripts, bearing, premature, nonsense, mutations])]). relacion([sujeto(['The', levels, of, the, shorter, 'cyc1-512', transcripts, were]), verbo([enhanced]), complemento([in, the, 'cbc1-Delta', mutants, by, promoting, 3, '\'', -, end, formation, at, 'otherwise-weak', 'sites,', whereas, the, levels, of, the, longer, 'cyc1-512', 'transcripts,', as, well, as, of, all, 'mRNAs,', were, slightly, enhanced, by, diminishing, degradation])]). relacion([sujeto(['Furthermore,', 'cbc1-Delta', greatly]), verbo([suppressed]), complemento([the, degradation, of, mRNAs, and, other, phenotypes, of, a, 'rat7-1', strain, which, is, defective, in, mRNA, export])]). relacion([sujeto(['We']), verbo([suggest]), complemento([that, 'Cbc1p', defines, a, novel, degradation, pathway, that, acts, on, mRNAs, partially, retained, in, nuclei])]). relacion([sujeto(['Yeast', strains, lacking, the, yeast]), verbo([nuclear]), complemento(['cap-binding', complex, '(', 'yCBC)', are, 'viable,', although, impaired, in, growth])]). relacion([sujeto(['We']), verbo([have]), complemento([taken, advantage, of, this, observation, to, carry, out, a, genetic, screen, for, components, that, show, synthetic, lethality, '(', 'SL)', with, a, 'cbp20-Delta', 'cbp80-Delta', double, mutation])]). relacion([sujeto(['One', set, of, 'SL', interactions, was, due, to, mutations, that, were, complemented, by, components, of, 'U1', small]), verbo([nuclear]), complemento(['RNP', '(', 'snRNP)', and, the, yeast, splicing, commitment, complex])]). relacion([sujeto(['Physical', interaction, of, yCBC, with, the, commitment, complex, components, 'Mud10p', and, 'Mud2p,', which, may, directly]), verbo([mediate]), complemento([yCBC, 'function,', was, demonstrated])]). relacion([sujeto(['Mutants', lacking, yCBC, were]), verbo([found]), complemento([to, be, defective, in, rRNA, processing])]). relacion([sujeto(['Analysis', of, the, yCBC, deletion, phenotype]), verbo([suggests]), complemento([that, this, is, likely, to, be, due, to, a, defect, in, the, splicing, of, a, subset, of, ribosomal, protein, mRNA, precursors])]). relacion([sujeto(['In', an, attempt, to, further, understand, how]), verbo([nuclear]), complemento([events, '(', such, as, gene, 'expression,', nuclear, 'import/export,', and, cell, cycle, checkpoint, 'control)', might, be, subject, to, regulation, by, extracellular, 'stimuli,', we, sought, to, identify, nuclear, activities, under, growth, factor, control])]). relacion([sujeto(['Using', a, sensitive, photoaffinity, labeling, assay, that, measured, '[', 'alpha-32P]GTP', incorporation, into]), verbo([nuclear]), complemento(['proteins,', we, identified, the, 20, -, kDa, subunit, of, the, nuclear, 'cap-binding', complex, '(', 'CBC)', as, a, protein, whose, binding, activity, is, greatly, enhanced, by, the, extracellular, stimulation, of, 'serum-arrested', cells])]). relacion([sujeto(['The', 'CBC', represents, a, 20, -, and, 80, -, kDa, heterodimer, '(', the, subunits, independently, referred, to, as, 'CBP20', and, 'CBP80,', 'respectively)', that]), verbo([binds]), complemento([the, 7, -, methylguanosine, cap, on, 'RNAs', transcribed, by, 'RNA', polymerase, 'II'])]). relacion([sujeto(['This']), verbo([binding]), complemento([facilitates, precursor, messenger, 'RNA', splicing, and, export])]). relacion([sujeto(['We']), verbo([have]), complemento([demonstrated, that, the, '[', 'alpha-32P]GTP', incorporation, into, 'CBP20', was, correlated, with, an, increased, ability, of, the, 'CBC', to, bind, capped, 'RNA', and, have, used, the, '[', 'alpha-32P]GTP', photoaffinity, assay, to, characterize, the, activation, of, the, 'CBC', in, response, to, growth, factors])]). relacion([sujeto(['We', show, that, the, 'CBC', is]), verbo([activated]), complemento([by, heregulin, in, 'HeLa', cells, and, by, nerve, growth, factor, in, 'PC12', cells, as, well, as, during, the, 'G1/S', phase, of, the, cell, cycle, and, when, cells, are, stressed, with, 'UV', irradiation])]). relacion([sujeto(['Taken', 'together,', these, data, identify, the, 'CBC', as, a]), verbo([nuclear]), complemento([target, for, growth, 'factor-coupled', signal, transduction, and, suggest, novel, mechanisms, by, which, growth, factors, can, influence, gene, expression, and, cell, growth])]). relacion([sujeto(['Using', an, in, vivo, assay, 'system,']), verbo([nuclear]), complemento([import, ability, in, individual, cells, was, determined, by, examining, the, nuclear, import, rate])]). relacion([sujeto(['It', was]), verbo([found]), complemento([that, when, a, small, '(', not, 'excess)', amount, of, 'SV40', 'T-NLS', peptides, was, 'co-injected,', the, nuclear, import, rate, of, 'SV40', 'T-NLS-containing', substrates, apparently, increased])]). relacion([sujeto(['This', 'up-regulation', was, reproduced, by, the, 'co-injection', of, peptides, containing, bipartite, type, 'NLS', of, 'CBP80,', but, not, mutated, 'non-functional', 'NLS', 'peptides,', which]), verbo([suggests]), complemento([that, these, phenomena, are, specific, for, functional, 'NLSs'])]). relacion([sujeto(['It', was, further, shown, that, 'although,', in, 'growth-arrested', 'cells,', the]), verbo([nuclear]), complemento([import, rate, was, 'down-regulated', compared, to, growing, 'cells,', the, elevation, of, the, functional, import, rate, by, 'co-injected', 'NLS', peptides, reached, the, same, level, as, in, proliferating, cells])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, although, potential, nuclear, import, ability, does, not, vary, in, each, 'cell,', the, rate, of, nuclear, import, may, be, controlled, by, the, amount, of, karyophilic, 'proteins,', which, need, to, be, carried, into, the, nucleus, from, the, 'cytoplasm,', possibly, via, an, 'NLS-dependent', phosphorylation, reaction])]). relacion([sujeto(['Eukaryotic', mRNA, processing, and, export, is]), verbo([mediated]), complemento([by, various, heterogeneous, nuclear, ribonucleoproteins, '(', 'hnRNPs)'])]). relacion([sujeto(['Hmt1p', methylates, both, 'Npl3p', and, 'Hrp1p,', which, are, shuttling, hnRNPs]), verbo([involved]), complemento([in, mRNA, processing, and, export])]). relacion([sujeto(['Here,', we, employ, an, in, vivo]), verbo([nuclear]), complemento([export, assay, to, show, that, arginine, methylation, is, important, for, the, nuclear, export, of, these, hnRNPs])]). relacion([sujeto(['Both', 'Npl3p', and, 'Hrp1p', fail, to, exit, the, nucleus, in, cells, lacking, 'Hmt1p,', and, overexpression, of, 'Hmt1p']), verbo([enhances]), complemento(['Npl3p', export])]). relacion([sujeto(['The', export, of, a, novel, 'hnRNP-like', 'protein,', 'Hrb1p,', which, does, not]), verbo([bind]), complemento(['poly(A)+', 'RNA,', 'however,', is, not, affected, by, the, lack, of, methylation])]). relacion([sujeto(['Furthermore,', we]), verbo([find]), complemento([a, genetic, relationship, between, 'Hmt1p', and, 'cap-binding', protein, 80, '(', 'CBP80)'])]). relacion([sujeto([hnRNP, 'F', was, identified, in, a, screen, for, proteins, that]), verbo([interact]), complemento([with, human, 'CBP80', and, 'CBP20,', the, components, of, the, nuclear, 'cap-binding', complex, '(', 'CBC)'])]). relacion([sujeto(['In', vitro, interaction, studies, showed, that, hnRNP, 'F', can]), verbo([bind]), complemento([to, both, 'CBP20', and, 'CBP80', individually])]). relacion([sujeto([hnRNP, 'F', and, 'CBC']), verbo([bind]), complemento([independently, to, 'RNA,', but, hnRNP, 'F', binds, preferentially, to, 'CBC-RNA', complexes, rather, than, to, naked, 'RNA'])]). relacion([sujeto(['The', hnRNP, 'H', 'protein,', which, is, 78, '%', identical, to, hnRNP, 'F', and, also]), verbo([interacts]), complemento([with, both, 'CBP80', and, 'CBP20', in, 'vitro,', does, not, discriminate, between, naked, 'RNA', and, 'CBC-RNA', 'complexes,', showing, that, this, effect, is, specific])]). relacion([sujeto(['Depletion', of, hnRNP, 'F', from, 'HeLa', cell]), verbo([nuclear]), complemento([extract, decreases, the, efficiency, of, 'pre-mRNA', 'splicing,', a, defect, which, can, be, partially, compensated, by, addition, of, recombinant, hnRNP, 'F'])]). relacion([sujeto(['Thus,', hnRNP, 'F', is]), verbo([required]), complemento([for, efficient, 'pre-mRNA', splicing, in, vitro, and, may, participate, in, the, effect, of, 'CBC', on, 'pre-mRNA', splicing])]). relacion([sujeto(['In', 'vertebrates,', a]), verbo([nuclear]), complemento(['cap-binding', complex, '(', 'CBC)', formed, by, two, 'cap-', binding, 'proteins,', 'CBP20', and, 'CBP80,', is, involved, in, several, steps, of, 'RNA', 'metabolism,', including, 'pre-mRNA', splicing, and, nuclear, export, of, some, 'RNA', polymerase, 'II-transcribed', 'U', snRNAs])]). relacion([sujeto(['Using', immunoelectron, 'microscopy,', the, in, situ, association, of, 'CBP20', with, a, specific, 'pre-mRNP', 'particle,', the, 'Balbiani', ring, 'particle,']), verbo([has]), complemento([been, analyzed, at, different, stages, of, 'pre-mRNA', 'synthesis,', 'maturation,', and, 'nucleo-cytoplasmic', transport])]). relacion([sujeto(['We', demonstrate, that, 'CBP20']), verbo([binds]), complemento([to, the, nascent, 'pre-mRNA', shortly, after, transcription, 'initiation,', stays, in, the, 'RNP', particles, after, splicing, has, been, 'completed,', and, remains, attached, to, the, 5, '\'', domain, during, translocation, of, the, 'RNP', through, the, nuclear, pore, complex, '(', 'NPC)'])]). relacion([sujeto(['The', effect, of, the, cap, on, translation, is]), verbo([mediated]), complemento([by, the, initiation, factor, 'eIF-4F,', whereas, the, effect, on, 'pre-mRNA', splicing, involves, a, nuclear, complex, '(', 'CBC)', composed, of, two, cap, binding, 'proteins,', 'CBP80', and, 'CBP20'])]). relacion([sujeto(['A', role, for, 'CBC', in, the]), verbo([nuclear]), complemento([export, of, capped, 'RNAs', has, also, been, proposed])]). relacion([sujeto(['We']), verbo([report]), complemento([here, the, characterization, of, human, and, 'Xenopus', 'CBP20s'])]). relacion([sujeto(['Antibodies', against, recombinant, 'CBP20']), verbo([prevent]), complemento([interaction, of, 'CBC', with, capped, 'RNAs', in, vitro])]). relacion([sujeto(['Following', microinjection, into, 'Xenopus', 'oocytes,', the, antibodies]), verbo([inhibit]), complemento([both, 'pre-mRNA', splicing, and, export, of, 'U', small, nuclear, 'RNAs', to, the, cytoplasm])]). relacion([sujeto(['These', results, demonstrate, that, 'CBC']), verbo([mediates]), complemento([the, effect, of, the, cap, structure, in, 'U', snRNA, 'export,', and, provide, direct, evidence, for, the, involvement, of, a, cellular, 'RNA-binding', factor, in, the, transport, of, 'RNA', to, the, cytoplasm])]). relacion([sujeto(['A', 'cap-binding', protein, complex, '(', 'CBC)', present, in, the, nuclei, of, 'HeLa', cells]), verbo([has]), complemento([been, characterized])]). relacion([sujeto(['Analysis', of, the, inhibition, of, 'pre-mRNA', splicing, in, vitro, and, in, vivo, by, chemically, modified, analogs, of, the, cap, 'structure,', and, of, the]), verbo([binding]), complemento([of, these, analogs, to, 'CBC', in, 'vitro,', suggests, a, role, for, the, complex, in, splicing])]). relacion([sujeto(['C2C12', myoblast, differentiation, on, the, 'ITO', electrode, was, validated, based, on]), verbo([decreases]), complemento([in, the, mRNA, level, of, 'MyoD', and, increases, in, the, mRNA, levels, of, myogenin, and, myosin, heavy, chain, '(', 'MHC)'])]). relacion([sujeto(['Postnatal', growth, and, repair, of, skeletal, muscle, relies, upon, a, population, of, quiescent, muscle, precursor, 'cells,', called, satellite, cells, that, can, be]), verbo([activated]), complemento([to, proliferate, and, differentiate, into, new, 'myofibers,', as, well, as, 'self-renew', to, replenish, the, satellite, cell, population])]). relacion([sujeto(['The', balance, between, differentiation, and, 'self-renewal', is, critical, to]), verbo([maintain]), complemento([muscle, tissue, 'homeostasis,', and, alterations, in, this, equilibrium, can, lead, to, chronic, muscle, degeneration])]). relacion([sujeto(['The', transcription, factor, 'CCAAT/enhancer']), verbo([binding]), complemento([protein, beta, '(', 'C/EBPβ)', is, expressed, in, 'Pax7(+)', satellite, cells, of, healthy, muscle, and, is, downregulated, during, myoblast, differentiation])]). relacion([sujeto(['Persistent', expression, of, 'C/EBPβ', upregulates, 'Pax7,']), verbo([inhibits]), complemento(['MyoD,', and, blocks, myogenic, differentiation])]). relacion([sujeto(['We']), verbo([find]), complemento([that, loss, of, 'C/EBPβ', leads, to, precocious, differentiation, at, the, expense, of, 'self-renewal', in, primary, myoblast, and, myofiber, cultures])]). relacion([sujeto(['We']), verbo([find]), complemento([that, 'C/EBPβ', can, regulate, 'Notch2', expression, and, that, restoration, of, 'Notch', activity, in, myoblasts, lacking, 'C/EBPβ', prevents, precocious, differentiation])]). relacion([sujeto(['These', findings, demonstrate, that, 'C/EBPβ', is, a, novel, regulator, of, satellite, cell, 'self-renewal', during, muscle, regeneration]), verbo([acting]), complemento([at, least, in, part, through, 'Notch2'])]). relacion([sujeto(['We', evaluated, whether, strength, training, '(', 'ST)', performed, prior, to, skeletal, muscle, cryolesion, would]), verbo([act]), complemento([as, a, 'preconditioning,', improving, skeletal, muscle, regeneration, and, responsiveness, to, 'low-level', laser, therapy, '(', 'LLLT)'])]). relacion([sujeto(['Forty-eight', hours, after, the, last, 'ST', 'session,', tibialis, anterior, '(', 'TA)', cryolesion, was]), verbo([induced]), complemento([and, 'LLLT', '(', 'InGaAlP,', 660, &, 'nbsp;nm,', 0.035, &, 'nbsp;W,', 4.9, &, 'nbsp;J/cm(2)/point,', 3, 'points,', spot, light, 0.028, &, 'nbsp;cm(2),', 14, &, 'nbsp;J/cm(2))', initiated, and, conducted, daily, for, 14, consecutive, days])]). relacion([sujeto(['Cryolesion']), verbo([induced]), complemento([massive, muscle, degeneration, associated, with, inflammatory, infiltrate])]). relacion([sujeto(['Cryolesion']), verbo([induced]), complemento([increased, 'TNF-α', levels, in, both, 'NE', +, 'LE', and, 'ST', +, 'LE', groups])]). relacion([sujeto(['Both', isolated, 'ST', and, 'LLLT']), verbo([increased]), complemento(['IL-10', levels, with, no, additional, effect])]). relacion([sujeto(['In', 'contrast,']), verbo([increased]), complemento(['TA', 'IL-6', levels, were, restricted, to, 'ST', and, 'ST', +, 'LE', +, 'LLLT', groups])]). relacion([sujeto(['Both', prior, 'ST', and, 'LLLT', therapies]), verbo([increased]), complemento(['MyoD', mRNA, levels, 'and,', 'interestingly,', combined, therapies, potentiated, this, response])]). relacion([sujeto(['Myf5', mRNA, levels, were]), verbo([increased]), complemento([only, in, 'ST', groups])]). relacion([sujeto(['Taken', 'together,', our, data]), verbo([provides]), complemento([evidences, for, prior, 'ST', potentiating, 'LLLT', efficacy, in, promoting, skeletal, muscle, regeneration])]). relacion([sujeto(['The', objective, of, this, study, is, to, explore, the, roles, of, macrophages, and, the, mechanisms]), verbo([involved]), complemento([in, the, regeneration, of, injured, skeletal, muscle])]). relacion([sujeto(['In', 'addition,', 'CL-liposomes', treatment]), verbo([decreased]), complemento([the, expression, of, regulatory, factors, of, muscle, regeneration, '(', 'HGF,', 'uPA,', 'COX-2,', 'IGF-1,', 'MGF,', 'FGF6),', and, increased, the, expression, of, inflammatory, cytokines, '(', 'TGF-β1,', 'TNF-α,', 'IL-1β,', 'RANTES)', in, the, late, stage, of, regeneration])]). relacion([sujeto(['These', results]), verbo([suggested]), complemento([that, macrophages, depletion, impairs, skeletal, muscle, 'regeneration,', and, that, the, regulatory, factors, for, muscle, regeneration, may, play, important, roles, in, this, process])]). relacion([sujeto(['At', a, lethal, concentration, '(', 100, 'μM),', nickel, treatment]), verbo([decreased]), complemento([the, space, between, gill, filaments, and, caused, epithelial, swelling, and, abnormal, fusion, of, gill, filaments])]). relacion([sujeto(['These', findings]), verbo([suggest]), complemento([that, nickel, affects, the, functional, development, of, 'gills,', leading, to, embryonic, death])]). relacion([sujeto(['At', 10, 'μM,', nickel, significantly]), verbo([decreased]), complemento([tail, length, and, tail, muscle, fiber, density, in, 'tadpoles,', indicating, inhibition, of, myogenic, differentiation])]). relacion([sujeto(['Calcium-dependent', kinase, activities, in, muscular, response, stage, embryos, were, significantly]), verbo([decreased]), complemento([by, 'nickel,', whereas, these, activities, were, restored, by, exogenous, calcium])]). relacion([sujeto(['In', 'tadpoles,', 10, μM, nickel, significantly]), verbo([decreased]), complemento([the, expression, of, the, myosin, heavy, chain, and, the, 12, /, 101, muscle, marker, protein, in, the, tail])]). relacion([sujeto(['In', the, present, study, we, show, that, palmitate, was, 'lipotoxic,']), verbo([inducing]), complemento([high, levels, of, cell, death, and, blocking, myotube, formation])]). relacion([sujeto(['Cell', death, under, these, conditions, was]), verbo([associated]), complemento([with, increased, caspase, 'activity,', suppression, of, 'differentiation,', reductions, in, both, creatine, kinase, activity, and, gene, expression, of, myogenic, 'factors;', 'IGF-II,', 'IGFBP-5,', 'MyoD', and, myogenin])]). relacion([sujeto(['By', 'contrast,', lipotoxicity]), verbo([associated]), complemento([with, elevated, palmitate, was, reduced, with, the, 'MEK', inhibitor, 'PD98059,', indicating, palmitate, induced, cell, death, was, 'MAPK', mediated])]). relacion([sujeto(['Addition', of, 'EPA', under, cytotoxic, stress, '(', 'TNF-α)', was, shown, to, partially, rescue, differentiation, with]), verbo([enhanced]), complemento([myotube, formation, being, associated, with, increased, 'MyoD,', 'myogenin,', 'IGF-II', and, 'IGFBP-5', expression])]). relacion([sujeto(['Additionally,', signalling, studies, indicated, the, combination, of, 'lipo-', and, 'cyto-toxic', effects, on, the, muscle, cells]), verbo([acted]), complemento([through, 'ceramide,', 'JNK', and, 'MAPK', pathways, and, blocking, these, pathways, using, 'PD98059', '(', 'MEK', 'inhibitor)', and, 'Fumonisin', 'B1', '(', ceramide, 'inhibitor)', significantly, reduced, levels, of, cell, death])]). relacion([sujeto(['These', findings, highlight, novel, pathways]), verbo([associated]), complemento([with, in, vitro, models, of, lipotoxicity, '(', 'palmitate-mediated)', and, cytotoxicity, '(', inflammatory, cytokine, 'mediated)', in, the, potential, targeting, of, molecular, modulators, of, sarcopenic, obesity])]). relacion([sujeto(['Quiescent', muscle, stem, cells, '(', 'MSC)', become]), verbo([activated]), complemento([in, response, to, skeletal, muscle, injury, to, initiate, regeneration])]). relacion([sujeto(['Activated', 'MSCs', proliferate, and, differentiate, to, repair, damaged, fibers, or, 'self-renew', to]), verbo([maintain]), complemento([the, pool, and, insure, future, regeneration])]). relacion([sujeto(['The', balance, between, 'self-renewal,', proliferation, and, differentiation, is, a, tightly]), verbo([regulated]), complemento([process, controlled, by, a, genetic, cascade, involving, determinant, transcription, factors, such, as, 'Pax7,', 'Myf5,', 'MyoD,', and, 'MyoG'])]). relacion([sujeto(['Recently', there]), verbo([have]), complemento([been, several, reports, about, the, role, of, arginine, methylation, as, a, requirement, for, 'epigenetic-mediated', control, of, muscle, regeneration])]). relacion([sujeto(['Herein', we]), verbo([report]), complemento([that, the, protein, arginine, methyltransferase, 1, '(', 'PRMT1)', is, expressed, in, 'MSCs', and, that, conditional, ablation, of, 'PRMT1', in, 'MSCs', using, 'Pax7(CreERT2)', causes, impairment, of, muscle, regeneration])]). relacion([sujeto(['Importantly,', 'PRMT1-deficient', 'MSCs']), verbo([have]), complemento([enhanced, cell, proliferation, after, 'injury,', but, are, unable, to, terminate, the, myogenic, differentiation, 'program,', leading, to, regeneration, failure])]). relacion([sujeto(['We', show, that, 'PRMT1', methylates, 'Eya1', in, vitro, and]), verbo([loss]), complemento([of, 'PRMT1', function, in, vivo, prevents, 'Eya1', methylation])]). relacion([sujeto(['Moreover,', we, observe, that, 'PRMT1-deficient', 'MSCs']), verbo([have]), complemento([reduced, expression, of, 'Eya1/Six1', targets, 'MyoD', due, to, disruption, of, 'Eya1', recruitment, at, 'MyoD', promoter, and, subsequent, 'Eya1-mediated', 'co-activation'])]). relacion([sujeto(['These', findings]), verbo([suggest]), complemento([that, arginine, methylation, by, 'PRMT1', regulates, muscle, stem, cell, fate, through, the, 'Eya1/Six1/MyoD', axis])]). relacion([sujeto(['In', untrained, 'individuals,', 'SC', content, and, activation, status]), verbo([has]), complemento([been, observed, to, increase, in, response, to, a, single, bout, of, exercise])]). relacion([sujeto(['Following', 16, wk, of, 'RT,', 'MyoD', mRNA, expression]), verbo([increased]), complemento([from, basal, to, 24, h, after, the, single, bout, of, exercise, '(', 'p<0'])]). relacion([sujeto(['Individual', 'capillary-to-fiber', ratio, '(', 'C/Fi)']), verbo([increased]), complemento([in, both, type, 'I', '(', 1.8, '±0'])]). relacion([sujeto(['Following', 'RT,']), verbo([enhanced]), complemento([activation, of, 'SC', in, response, to, resistance, exercise, is, accompanied, by, increases, in, muscle, fiber, capillarization])]). relacion([sujeto(['Hence,']), verbo([enhancing]), complemento([the, activity, of, 'MyoD', is, an, important, step, to, maximising, its, potential, utility, for, 'in vitro', disease, modelling, and, cell, replacement, therapies])]). relacion([sujeto(['We']), verbo([have]), complemento([previously, shown, that, the, reprogramming, activity, of, several, neurogenic, bHLH, proteins, can, be, substantially, enhanced, by, inhibiting, their, 'multi-site', phosphorylation, by, 'proline-directed', kinases])]). relacion([sujeto(['Here', we]), verbo([have]), complemento([used, 'Xenopus', embryos, as, an, 'in vivo', developmental, and, reprogramming, system, to, investigate, the, 'multi-site', 'phospho-regulation', of, 'MyoD', during, muscle, differentiation])]). relacion([sujeto(['We', show, 'that,', in, addition, to, modification, of, a, previously, 'well-characterised', 'site,', 'Serine', 200, ',', 'MyoD', is]), verbo([phosphorylated]), complemento([on, multiple, additional, 'serine/threonine', sites, during, primary, myogenesis])]). relacion([sujeto(['Through', mutational, 'analysis,', we, derive, an, optimally, active, 'phospho-mutant', form, of, 'MyoD', that]), verbo([has]), complemento([a, dramatically, enhanced, ability, to, drive, myogenic, reprogramming, 'in vivo'])]). relacion([sujeto(['Mechanistically,', this, is, achieved, through]), verbo([increased]), complemento([protein, stability, and, enhanced, chromatin, association])]). relacion([sujeto(['Therefore,', 'multi-site', 'phospho-regulation', of, class, 'II', bHLH, proteins, is]), verbo([conserved]), complemento([across, cell, lineages, and, germ, 'layers,', and, manipulation, of, phosphorylation, of, these, key, regulators, may, have, further, potential, for, enhancing, mammalian, cell, reprogramming])]). relacion([sujeto(['To', identify, the, molecules]), verbo([involved]), complemento([in, epithelial, to, mesenchymal, transition, '(', 'EMT)', in, urothelial, carcinoma, '(', 'UC)', after, acquisition, of, platinum, 'resistance,', here, we, examined, the, changes, in, global, gene, expression, before, and, after, platinum, treatment])]). relacion([sujeto(['In', vitro, and, in, vivo, studies, showed, an, intimate, relationship, between, 'FBXO32', expression, and, 'EMT,', demonstrating, that, 'FBXO32', dysregulation, in, 'T24PR', cells, results, in, elevated, expression, of, the, mesenchymal, molecules, 'SNAIL', and, vimentin, and]), verbo([decreased]), complemento([expression, of, the, epithelial, molecule, 'E-cadherin'])]). relacion([sujeto(['Knockdown', of, 'MyoD', 'expression,', a, specific]), verbo([target]), complemento([of, 'FBXO32', 'polyubiquitination,', revealed, upregulation, of, 'E-cadherin', expression, and, downregulation, of, 'SNAIL', and, vimentin, expression, in, 'T24PR', cells])]). relacion([sujeto(['Comparative', genomic, hybridization, array, analysis, demonstrated]), verbo([loss]), complemento([of, heterozygosity, at, 8, q24])]). relacion([sujeto(['Our', findings]), verbo([suggest]), complemento([the, importance, of, the, association, between, 'EMT', and, 'ubiquitin-proteasome', regulation, when, tumors, develop, acquired, platinum, resistance])]). relacion([sujeto(['In', the, undifferentiated, 'condition,', 'Pax7', expression, in, 'MyoD', 'KO', 'QM7#4', cells, was, not, significantly, different, from]), verbo([regular]), complemento(['QM7', '(', 'rQM7)', cells])]). relacion([sujeto(['Moreover,', myogenic, 'differentiation-specific', transcripts, and, proteins, were, not]), verbo([expressed]), complemento([in, 'MyoD', 'QM7', 'KO#4', cells, even, after, an, extended, differentiation, period])]). relacion([sujeto(['Avian', broilers]), verbo([have]), complemento([been, genetically, selected, based, on, their, high, growth, velocity, and, large, muscle, mass])]). relacion([sujeto(['The', expression, of, 'Pax7', followed, a, downward, 'trend,', whereas, that, of, 'MyoD', and, 'IGF-1', first]), verbo([increased]), complemento([and, subsequently, decreased, in, cells, isolated, from, the, two, chickens])]). relacion([sujeto(['We']), verbo([suggest]), complemento([that, the, methods, of, breeding, selection, applied, to, these, breeds, regulate, the, characteristics, of, skeletal, muscle, satellite, cells, to, influence, muscle, growth])]). relacion([sujeto(['Muscles', of, old, animals, are, injured, more, easily, and, regenerate, 'poorly,', attributed, in, part, to]), verbo([increased]), complemento([levels, of, circulating, 'pro-inflammatory', cytokines])]). relacion([sujeto(['The', 'Janus', 'kinase/signal', transducers, and, activators, of, transcription, '(', 'JAK/STAT)', signaling, cascade, is, a, key, mediator, of, inflammatory, cytokine, 'action,', and, signaling, via, this, pathway, is]), verbo([increased]), complemento([in, muscles, with, aging])]). relacion([sujeto(['As', a, negative, regulator, of, 'JAK/STAT', 'signaling,', a, key, mediator, of, myogenic, proliferation, and, 'differentiation,', altered, expression, of, suppressor, of, cytokine, signaling, '(', 'SOCS3)', is, likely, to]), verbo([have]), complemento([important, consequences, for, muscle, regeneration])]). relacion([sujeto(['In', uninjured, 'muscles,', 'SOCS3', deletion]), verbo([decreased]), complemento([force, production, during, fatigue, but, had, no, effect, on, the, gross, or, histological, appearance, of, the, 'TA', muscles])]). relacion([sujeto(['After', notexin, 'injury,', deletion, of, 'SOCS3']), verbo([increased]), complemento(['STAT3', phosphorylation, at, day, 1, and, increased, the, mRNA, expression, of, the, inflammatory, cytokine, 'TNF-α,', and, the, inflammatory, cell, markers, 'F4/80', and, 'CD68', at, day, 2])]). relacion([sujeto(['Loss', of, 'SOCS3', expression, in, mature, muscle, fibers]), verbo([increased]), complemento([the, inflammatory, response, to, myotoxic, injury, but, did, not, impair, muscle, regeneration, in, either, adult, or, old, mice])]). relacion([sujeto(['Further', investigation, into, the, role, of, 'SOCS3', in, other, cell, types]), verbo([involved]), complemento([in, muscle, repair, is, warranted])]). relacion([sujeto(['MicroRNAs', '(', 'miRNAs)', are, highly, 'conserved,', short, 'non-coding', 'RNAs', that]), verbo([regulate]), complemento([gene, expression, at, the, posttranscriptional, level])]). relacion([sujeto(['Our', results, demonstrated, that, 'i)', 'miR-127-3p', was, extensively]), verbo([expressed]), complemento([in, tissues, of, 'goats;', 'ii)', 'miR-127-3p', was, higher, expressed, in, 'muscle,', 'spleen,', 'heart,', and, skin, in, the, muscular, goats, '(', 'Boer', 'goats)', than, the, control, '(', 'Wushan', black, 'goats)'])]). relacion([sujeto(['Especially,', we]), verbo([found]), complemento([that, 'miR-127-3p', was, significantly, higher, expressed, in, the, proliferating, than, differentiating, cells])]). relacion([sujeto(['Our', findings]), verbo([suggest]), complemento([that, 'miR-127-3p', probably, plays, roles, in, the, proliferation, and, differentiation, of, 'myoblasts,', which, further, underlies, regulation, of, muscle, phenotype, in, goats])]). relacion([sujeto(['TPA', 'Induced', 'Sequence', 7]), verbo([acts]), complemento([as, a, transcriptional, 'co-regulator', controlling, the, expression, of, genes, involved, in, differentiation, of, various, cell, 'types,', including, skeletal, myoblasts])]). relacion([sujeto(['We', and, others]), verbo([have]), complemento([shown, that, 'TIS7', regulates, adult, myogenesis, through, 'MyoD,', one, of, the, essential, myogenic, regulatory, factors])]). relacion([sujeto(['We', show, that, 'TIS7/ICln', epigenetically]), verbo([regulate]), complemento([myoD, expression, controlling, protein, methyl, transferase, activity])]). relacion([sujeto(['In', 'particular,', 'ICln']), verbo([regulates]), complemento(['MyoD', expression, via, its, interaction, with, 'PRMT5', by, an, epigenetic, modification, that, utilizes, symmetrical, 'di-methylation', of, histone, 'H3', on, arginine, 8])]). relacion([sujeto(['We']), verbo([provide]), complemento([multiple, evidences, that, 'TIS7', directly, binds, 'DNA,', which, is, a, functional, feature, necessary, for, its, role, in, transcriptional, regulation])]). relacion([sujeto(['Protein', 4.1, 'R', '(', 4.1, 'R)', isoforms, are]), verbo([expressed]), complemento([in, both, cardiac, and, skeletal, muscle])]). relacion([sujeto(['It', is, also]), verbo([associated]), complemento([with, dystrophin, at, the, sarcolemma, in, skeletal, myofibers])]). relacion([sujeto(['However,', the, expression, and, function, of, 4.1, 'R', during, myogenesis]), verbo([have]), complemento([not, been, characterized])]). relacion([sujeto(['We', now]), verbo([report]), complemento([that, 4.1, 'R', expression, increases, during, 'C2C12', myoblast, differentiation, into, myotubes])]). relacion([sujeto(['Depletion', of, 4.1, 'R', impairs, skeletal, muscle, differentiation, and, is, accompanied, by, a]), verbo([decrease]), complemento([in, the, levels, of, myosin, heavy, and, light, chains, and, 'caveolin-3'])]). relacion([sujeto(['Furthermore,', the, expression, of, myogenin, at, the, 'protein,', but, not, 'mRNA,', level, is, drastically]), verbo([decreased]), complemento([in, 4.1, 'R', knockdown, myocytes])]). relacion([sujeto(['We', show, that, 4.1, 'R']), verbo([associates]), complemento([with, 'VHL', 'and,', when, 'overexpressed,', reverses, myogenin, ubiquitination, and, stability])]). relacion([sujeto(['This']), verbo([suggests]), complemento([that, 4.1, 'R', may, influence, myogenesis, by, preventing, 'VHL-mediated', myogenin, degradation])]). relacion([sujeto(['Together,', our, results, define, a, novel, biological, function, for, 4.1, 'R', in, muscle, differentiation, and]), verbo([provide]), complemento([a, molecular, mechanism, by, which, 4.1, 'R', promotes, myogenic, differentiation])]). relacion([sujeto(['Cdkn1c', protein, levels, are, carefully]), verbo([regulated]), complemento([via, imprinting, and, other, epigenetic, mechanisms, affecting, both, the, promoter, and, distant, regulatory, 'elements,', which, restrict, its, expression, to, particular, developmental, phases, or, specific, cell, types])]). relacion([sujeto(['Inappropriate', activation, of, these, regulatory, mechanisms]), verbo([leads]), complemento([to, 'Cdkn1c', 'silencing,', causing, growth, disorders, and, cancer])]). relacion([sujeto(['We']), verbo([have]), complemento([previously, reported, 'that,', in, skeletal, muscle, 'cells,', induction, of, 'Cdkn1c', expression, requires, the, binding, of, the, bHLH, myogenic, factor, 'MyoD', to, a, 'long-distance', regulatory, element, within, the, imprinting, control, region, 'KvDMR1'])]). relacion([sujeto(['Interestingly,', 'MyoD']), verbo([binding]), complemento([to, 'KvDMR1', is, prevented, in, myogenic, cell, types, refractory, to, the, induction, of, 'Cdkn1c'])]). relacion([sujeto(['We', show, that, treatment, with, the, 'DNA', demethylating, agent, 5, -, azacytidine, restores, the]), verbo([binding]), complemento([of, 'MyoD', to, 'KvDMR1', in, cells, unresponsive, to, 'Cdkn1c', induction])]). relacion([sujeto(['This,', in, 'turn,']), verbo([promotes]), complemento([the, release, of, a, repressive, chromatin, loop, between, 'KvDMR1', and, 'Cdkn1c', promoter, 'and,', 'thus,', the, upregulation, of, the, gene])]). relacion([sujeto(['Analysis', of, the, chromatin, status, of, 'Cdkn1c', promoter, and, 'KvDMR1', in, unresponsive, compared, to, responsive, cell, types, showed, that, their, differential, responsiveness, to, the, 'MyoD-dependent', induction, of, the, gene, does, not]), verbo([involve]), complemento([just, their, methylation, status, 'but,', 'rather,', the, differential, 'H3', lysine, 9, dimethylation, at, 'KvDMR1'])]). relacion([sujeto(['Finally,', we]), verbo([report]), complemento([that, the, same, histone, modification, also, marks, the, 'KvDMR1', region, of, human, cancer, cells, in, which, 'Cdkn1c', is, silenced])]). relacion([sujeto(['On', the, basis, of, these, 'results,', we]), verbo([suggest]), complemento([that, the, epigenetic, status, of, 'KvDMR1', represents, a, critical, determinant, of, the, cell, 'type-restricted', expression, of, 'Cdkn1c', 'and,', 'possibly,', of, its, aberrant, silencing, in, some, pathological, conditions])]). relacion([sujeto(['During', muscle, regeneration, after, injury, '(', cardiotoxin, 'injection),', 'Klf5', was]), verbo([induced]), complemento([in, the, nuclei, of, differentiating, myoblasts, and, newly, formed, myofibers, expressing, myogenin, in, vivo])]). relacion([sujeto(['Satellite', 'cell-specific', 'Klf5', deletion, severely, impaired, muscle, 'regeneration,', and, myotube, formation, was]), verbo([suppressed]), complemento([in, 'Klf5-deleted', cultured, 'C2C12', myoblasts, and, satellite, cells])]). relacion([sujeto(['Klf5', knockdown]), verbo([suppressed]), complemento([induction, of, muscle, 'differentiation-related', 'genes,', including, myogenin])]). relacion([sujeto(['Klf5', 'ChIP-seq', revealed, that, 'Klf5']), verbo([binding]), complemento([overlaps, that, of, 'MyoD', and, 'Mef2,', and, 'Klf5', physically, associates, with, both, 'MyoD', and, 'Mef2'])]). relacion([sujeto(['These', results, indicate, that, 'Klf5', is, an, essential, regulator, of, skeletal, muscle, 'differentiation,']), verbo([acting]), complemento([in, concert, with, myogenic, transcription, factors, such, as, 'MyoD', and, 'Mef2'])]). relacion([sujeto(['I-mfa', '(', inhibitor, of, the, 'MyoD', family, 'a)', is, a, transcription, modulator, that]), verbo([binds]), complemento([to, 'MyoD', family, members, and, inhibits, their, transcriptional, activities])]). relacion([sujeto(['It', is, highly]), verbo([expressed]), complemento([in, the, sclerotome, and, plays, an, important, role, in, the, patterning, of, the, somite, early, in, development])]). relacion([sujeto(['The', statistical, analyses, indicated, that, the, three, 'SNPs,', are]), verbo([associated]), complemento([with, the, phenotypic, traits, in, 'Luxi', '(', 'LX),', 'Qinchuan', '(', 'QC),', and, 'Jiaxian', '(', 'JX)', cattle, population, '(', 'P < 0'])]). relacion([sujeto(['The', 'mutant-type', variants, were, superior, for, growth, 'traits;', the, heterozygote, diplotype, was]), verbo([associated]), complemento([with, higher, growth, traits, compared, to, 'wild-type', homozygote])]). relacion([sujeto(['Our', results]), verbo([provide]), complemento([evidence, that, polymorphisms, in, the, 'I-mfa', gene, are, associated, with, growth, traits, and, may, be, used, for, 'marker-assisted', selection, in, beef, cattle, breeding, program])]). relacion([sujeto(['I-mfa', null, mice]), verbo([have]), complemento([an, osteopenic, phenotype, characterized, by, increased, osteoclast, numbers, and, 'surface,', which, are, normalized, in, mice, lacking, both, 'Trpc1', and, 'I-mfa'])]). relacion([sujeto(['In', vitro, differentiation, of, 'pre-osteoclasts', derived, from, 'I-mfa-deficient', mice]), verbo([leads]), complemento([to, an, increased, number, of, mature, osteoclasts, and, higher, bone, resorption, per, osteoclast])]). relacion([sujeto(['Consistently,', whole, cell, currents]), verbo([activated]), complemento([in, response, to, the, depletion, of, intracellular, 'Ca(2+)', stores, are, larger, in, 'pre-osteoclasts', derived, from, 'I-mfa', 'knock-out', mice, compared, with, currents, in, wild, type, mice, and, normalized, in, cells, derived, from, double, mutant, 'mice,', suggesting, a, 'cell-autonomous', effect, of, 'I-mfa', on, 'TRPC1', in, these, cells])]). relacion([sujeto(['Heterologous', expression, of, 'TRPC1ε', in, 'HEK293', cells, revealed, that, it, is, unique, among, all, known, 'TRPC1', isoforms, in, its, ability, to, amplify, the, activity, of, the, 'Ca(2+)', 'release-activated', 'Ca(2+)', '(', 'CRAC)', 'channel,']), verbo([mediating]), complemento(['store-operated', currents])]). relacion([sujeto(['TRPC1ε', physically]), verbo([interacts]), complemento([with, 'Orai1,', the, 'pore-forming', subunit, of, the, 'CRAC', 'channel,', and, 'I-mfa', is, recruited, to, the, 'TRPC1ε-Orai1', complex, through, 'TRPC1ε', suppressing, 'CRAC', channel, activity])]). relacion([sujeto(['We', propose, that, the, positive, and, negative, modulation, of, the, 'CRAC', channel, by, 'TRPC1ε', and, 'I-mfa,', 'respectively,', 'fine-tunes', the, dynamic, range, of, the, 'CRAC', channel]), verbo([regulating]), complemento([osteoclastogenesis])]). relacion([sujeto(['We', identify, a, novel, interaction, of, 'Hand1', with, a, protein, that, contains, an, 'I-mfa', '(', inhibitor, of, myogenic, 'factor)', domain, that, anchors, 'Hand1', in, the, nucleolus, where, it, negatively]), verbo([regulates]), complemento(['Hand1', activity])]). relacion([sujeto(['In', the, trophoblast, 'stem-cell', line, 'Rcho-1,', nucleolar, sequestration, of, 'Hand1', accompanies, sustained, cell, proliferation, and, 'renewal,', whereas]), verbo([release]), complemento([of, 'Hand1', into, the, nucleus, leads, to, its, 'activation,', thus, committing, cells, to, a, differentiated, 'giant-cell', fate])]). relacion([sujeto(['Site-specific', phosphorylation, is]), verbo([required]), complemento([for, nucleolar, release, of, 'Hand1,', for, its, dimerization, and, biological, 'function,', and, this, is, mediated, by, the, 'non-canonical', 'polo-like', kinase, 'Plk4', '(', 'Sak)'])]). relacion([sujeto(['Sak', is, 'co-expressed', in, 'Rcho-1', 'cells,', localizes, to, the, nucleolus, during, 'G2', and]), verbo([phosphorylates]), complemento(['Hand1', as, a, requirement, for, trophoblast, 'stem-cell', commitment, to, a, 'giant-cell', fate])]). relacion([sujeto(['This', study, defines, a, novel, cellular, mechanism, for]), verbo([regulating]), complemento(['Hand1', that, is, a, crucial, step, in, the, 'stem-cell', differentiation, pathway])]). relacion([sujeto(['Transient', receptor, potential, canonical, 1, '(', 'TRPC1)', is, a, transmembrane, protein]), verbo([expressed]), complemento([in, a, range, of, vertebrate, cells, including, smooth, 'muscle,', 'endothelium,', neurones, and, salivary, gland, cells])]). relacion([sujeto(['It', functions, as, an, element, of, a, mixed, cationic, 'Ca(2+)-permeable', 'channel,', probably, commonly, as, part, of, a, heterotetrameric, assembly]), verbo([involving]), complemento([other, related, proteins, such, as, 'TRPC5'])]). relacion([sujeto(['Wide-ranging', biological, roles, of, 'TRPC1', are, 'suggested,', including, regulation, of, smooth, muscle, and, stem, cell, 'proliferation,', 'endothelin-evoked', arterial, 'contraction,', salivary, gland, 'secretion,', endothelial, 'permeability,', glutamatergic, 'neurotransmission,', growth, cone, 'turning,', 'neuroprotection,', neuronal, 'differentiation,', lipid, raft, integrity, and, the]), verbo([nuclear]), complemento([factor, of, activated, 'T-cell', transcription, factor])]). relacion([sujeto(['At', one, 'level,', it, is, apparent, that, 'TRPC1', is, subcellularly, 'compartmentalised,', at, least, in, part, in, 'cholesterol-rich', caveolae, closely]), verbo([associated]), complemento([with, 'sub-plasmalemmal', endoplasmic, reticulum])]). relacion([sujeto(['It', is, also, apparent, that, 'TRPC1']), verbo([responds]), complemento([to, general, 'stimuli-not', only, depletion, of, intracellular, 'Ca(2+)', 'stores,', but, also, receptor, 'activation,', and, membrane, stretch])]). relacion([sujeto(['We', are, at, the, early, stages, of, understanding, of, how, these, various, signals, and, components, integrate, to, form, a, functional, 'channel,', and, this, article]), verbo([provides]), complemento([a, brief, overview, of, current, progress])]). relacion([sujeto(['Descriptive', studies]), verbo([have]), complemento([shown, that, several, of, these, factors, are, also, expressed, in, the, human, 'placenta,', suggesting, that, the, molecular, mechanisms, governing, trophoblast, differentiation, could, be, similar, in, mice, and, men])]). relacion([sujeto(['While', an]), verbo([increasing]), complemento([number, of, putative, developmental, regulators, are, being, identified, in, the, human, 'placenta,', little, information, is, available, regarding, whether, the, particular, factors, play, an, essential, role, in, trophoblast, differentiation, processes, such, as, formation, of, anchoring, 'villi,', placental, bed, invasion, or, syncytialization])]). relacion([sujeto(['However,', expression, of, abundant, 'trophoblast-specific', products, such, as, hormones, can, be, regarded, as, a, hallmark, of, 'differentiation,']), verbo([suggesting]), complemento([that, the, factors, controlling, their, transcription, could, also, be, involved, in, the, developmental, processes, of, the, placenta])]). relacion([sujeto(['Indeed,', studies, in, different, model, systems, revealed, that, the, human, homologues, of, murine, 'trophoblast-specific', transcriptional, regulators]), verbo([interact]), complemento([with, the, promoter, regions, of, typical, placental, genes, such, as, aromatase, 'P450', '(', 'CYP19),', chorionic, gonadotrophin, '(', 'CG)', or, placental, lactogen, '(', 'PL)'])]). relacion([sujeto(['Additionally,', the, unique, combination, of, more, broadly, distributed, transcription, factors, of, the, 'Sp', or, 'Ap-2', protein, family, in, a, particular, trophoblast, cell, type, is]), verbo([required]), complemento([to, govern, mRNA, expression, in, a, 'differentiation-dependent', manner])]). relacion([sujeto(['Here,', we, will, summarize, our, present, knowledge, on, these, individual, transcription, factors, that, are]), verbo([involved]), complemento([in, human, trophoblast, function, and, differentiation])]). relacion([sujeto(['We']), verbo([have]), complemento([determined, that, 'I-mfa,', an, inhibitor, of, several, basic, 'helix-loop-helix', '(', 'bHLH)', 'proteins,', and, 'XIC,', a, 'Xenopus', ortholog, of, human, 'I-mf', 'domain-containing', protein, that, shares, a, highly, conserved, 'cysteine-rich', 'C-terminal', domain, with, 'I-mfa,', inhibit, the, activity, and, 'DNA', binding, of, the, 'HMG', box, transcription, factor, 'XTcf3'])]). relacion([sujeto(['Ectopic', expression, of, 'I-mfa', or, 'XIC', in, early, 'Xenopus', embryos]), verbo([inhibited]), complemento([dorsal, axis, 'specification,', the, expression, of, the, 'Tcf3/beta-catenin-regulated', genes, siamois, and, 'Xnr3,', and, the, ability, of, 'beta-catenin', to, activate, reporter, constructs, driven, by, 'Lef/Tcf', binding, sites])]). relacion([sujeto(['I-mfa', domain, proteins, can]), verbo([regulate]), complemento([both, the, 'Wnt', signaling, pathway, and, a, subset, of, bHLH, 'proteins,', possibly, coordinating, the, activities, of, these, two, critical, developmental, pathways])]). relacion([sujeto(['The', 'I-mfa', domain, proteins, 'HIC', '(', also, known, as, 'MDFIC)', and, 'I-mfa', '(', also, known, as, 'MDFI)', are, candidate, tumor, suppressor, genes, that, are]), verbo([involved]), complemento([in, cellular, and, viral, transcriptional, regulation])]). relacion([sujeto(['Here,', we, show, that, 'HIC', and, 'I-mfa', directly]), verbo([interact]), complemento([with, human, 'T-cell', leukemia, virus, 'type-1', '(', 'HTLV-1)', 'Tax', protein, in, vitro])]). relacion([sujeto(['HIC', also]), verbo([interacts]), complemento([with, 'Tax', through, its, 'I-mfa', domain, in, vivo, and, represses, 'Tax-dependent', transactivation, of, 'HTLV-1', 'LTR', and, 'NF-κB', reporter, constructs, in, an, 'interaction-dependent', manner])]). relacion([sujeto(['Furthermore,', we, show, that, 'HIC']), verbo([decreases]), complemento([the, nuclear, distribution, and, stimulates, the, proteasomal, degradation, of, 'Tax'])]). relacion([sujeto(['These', data]), verbo([reveal]), complemento([that, 'HIC', specifically, interacts, with, 'HTLV-1', 'Tax', and, negatively, regulates, 'Tax', transactivational, activity, by, altering, its, subcellular, distribution, and, stability])]). relacion([sujeto(['Here', we, demonstrate, that, 'Zic3', can]), verbo([suppress]), complemento(['Wnt/β-catenin', signaling, and, control, development, of, the, notochord, and, 'Spemann\'s', organizer])]). relacion([sujeto(['Co-injection', of, 'Siamois', 'RNA', partially, rescued, the, reduction, of, 'Xnot', expression]), verbo([caused]), complemento([by, 'Zic3', overexpression])]). relacion([sujeto(['Co-injection', of, 'Xenopus', 'Zic', 'RNAs', and, 'β-catenin', 'RNA', with, a, reporter, responsive, to, the, 'Wnt/β-catenin', cascade, indicated, that, 'Zic1,', 'Zic2,', 'Zic3,', 'Zic4,', and, 'Zic5', can, all]), verbo([suppress]), complemento(['β-catenin-mediated', transcriptional, activation])]). relacion([sujeto(['In', 'addition,', 'co-injection', of, 'Zic3', 'RNA']), verbo([inhibited]), complemento([the, secondary, axis, formation, caused, by, 'ventral-side', injection, of, 'β-catenin', 'RNA', in, 'Xenopus', embryos])]). relacion([sujeto(['Zic3-mediated', 'Wnt/β-catenin', signal, suppression]), verbo([required]), complemento([the, nuclear, localization, of, 'Zic3,', and, involved, the, reduction, of, 'β-catenin', nuclear, transport, and, enhancement, of, 'β-catenin', degradation])]). relacion([sujeto(['Furthermore,', 'Zic3', 'co-precipitated', with, 'Tcf1', '(', a, 'β-catenin', 'co-factor)', and, 'XIC', '(', 'I-mfa', domain, containing, factor]), verbo([required]), complemento([for, dorsoanterior, 'development)'])]). relacion([sujeto(['The', findings, in, this]), verbo([report]), complemento([produce, a, novel, system, for, 'fine-tuning', of, 'Wnt/β-catenin', signaling])]). relacion([sujeto(['The', 'I-mfa', domain, proteins, 'I-mfa', and, 'HIC', are, considered, to, be, candidate, tumor, suppressor, genes, and]), verbo([have]), complemento([been, shown, to, be, involved, in, transcriptional, regulation])]). relacion([sujeto(['We', show, here, that, 'I-mfa', and, 'HIC', specifically]), verbo([interact]), complemento([with, 'SEI-1', through, their, 'C-terminal', 'I-mfa', domains, 'in vivo'])]). relacion([sujeto(['This', interaction, affects, the, intracellular, localization, of, 'I-mfa', and]), verbo([requires]), complemento([the, region, of, 'SEI-1', between, 30, and, 90, amino, 'acids,', which, includes, its, 'SERTA', 'domain,', and, results, in, repression, of, its, intrinsic, transcriptional, activity])]). relacion([sujeto(['I-mfa', also]), verbo([decreases]), complemento([the, levels, of, the, 'SEI-1·DP-1', complex, and, endogenous, 'Fbxw7', 'mRNA,', the, expression, of, which, is, coregulated, by, 'E2F·DP-1', and, 'SEI-1', in, an, 'interaction-dependent', manner, 'in vitro'])]). relacion([sujeto(['In', 'addition,', 'I-mfa', also, specifically]), verbo([interacts]), complemento([with, other, 'SERTA', 'domain-containing', 'proteins,', including, 'SEI-2,', 'SEI-3,', 'SERTAD3', and, 'SERTAD4,', through, its, 'I-mfa', domain, 'in vivo'])]). relacion([sujeto(['This', interaction, also, affects, the, intracellular, localization, of, 'I-mfa', and, represses, the, intrinsic, transcriptional, activities, of, 'SEI-2', and, 'SERTAD3,', which, are, also]), verbo([involved]), complemento([in, the, 'E2F-dependent', transcription])]). relacion([sujeto(['These', data]), verbo([reveal]), complemento([for, the, first, time, that, 'I-mfa', domain, proteins, interact, with, 'SERTA', domain, proteins, and, negatively, regulate, their, transcriptional, activity])]). relacion([sujeto(['Because', 'SEI-1,', 'SEI-2', and, 'SERTAD3,', whose, intrinsic, transcriptional, activities, are, repressed, by, 'I-mfa,', are]), verbo([suggested]), complemento([to, be, 'oncogenes,', 'I-mfa', domain, proteins, may, be, involved, in, their, oncogenic, functions, by, negatively, regulating, their, transcriptional, activities])]). relacion([sujeto(['The', 'HIV-1', regulatory, protein, 'Rev,', which, is, essential, for, viral, 'replication,']), verbo([mediates]), complemento([the, nuclear, export, of, unspliced, viral, transcripts])]). relacion([sujeto(['Rev']), verbo([nuclear]), complemento([function, requires, active, nucleocytoplasmic, 'shuttling,', and, 'Rev', nuclear, import, is, mediated, by, the, recognition, of, its, 'Nuclear', 'Localisation', 'Signal', '(', 'NLS)', by, multiple, import, 'factors,', which, include, transportin, and, importin, β])]). relacion([sujeto(['However,', it, remains, unclear, which]), verbo([nuclear]), complemento([import, 'pathway(s)', predominate, in, 'vivo,', and, the, cellular, environment, that, modulates, 'Rev', nucleocytoplasmic, shuttling, remains, to, be, characterised])]). relacion([sujeto(['In', our, 'study,', we]), verbo([have]), complemento([identified, the, cellular, protein, 'HIC', '(', 'Human', 'I-mfa', 'domain-Containing', 'protein)', as, a, novel, interactor, of, 'HIV-1', 'Rev'])]). relacion([sujeto(['We', demonstrate, that, 'HIC', selectively, interferes, with, 'Rev', 'NLS', interaction, with, importin, β, and, impedes, its]), verbo([nuclear]), complemento([import, and, 'function,', but, does, not, affect, 'Rev', nuclear, import, mediated, by, transportin])]). relacion([sujeto(['Hence,', the, molecular, determinants]), verbo([mediating]), complemento(['Rev-NLS', recognition, by, importin, β, and, transportin, appear, to, be, distinct])]). relacion([sujeto(['Furthermore,', we]), verbo([have]), complemento([employed, 'HIC', and, 'M9', 'M,', a, peptide, specifically, designed, to, inhibit, the, 'transportin-mediated', nuclear, import, 'pathway,', to, characterise, 'Rev', nuclear, import, pathways, within, different, cellular, environments])]). relacion([sujeto(['Remarkably,', we, could, show, that, in, 293, 'T,', 'HeLa,', 'COS7,', 'Jurkat,', 'U937,', 'THP-1', and, 'CEM', 'cells,', 'Rev']), verbo([nuclear]), complemento([import, is, cell, type, specific, and, alternatively, mediated, by, transportin, or, importin, 'β,', in, a, mutually, exclusive, fashion])]). relacion([sujeto(['These', studies, highlight, that, the, multivalent, nature, of, the, 'Rev', 'NLS', for, different, import, receptors, enables, 'Rev', to, adapt, its]), verbo([nuclear]), complemento([trafficking, strategy])]). relacion([sujeto(['Kaposi\'s', 'sarcoma-associated', herpes, virus, '(', 'KSHV)-encoded', 'latency-associated']), verbo([nuclear]), complemento([antigen, '(', 'LANA)', protein, has, been, reported, to, interact, with, glycogen, synthase, kinase, 3, beta, '(', 'GSK-3beta)', and, to, negatively, regulate, its, 'activity,', leading, to, stimulation, of, 'GSK-3beta-dependent', 'beta-catenin', degradation])]). relacion([sujeto(['We', show, here, that, the, 'I-mfa', domain, 'proteins,', 'HIC', '(', human, 'I-mfa', 'domain-containing', 'protein)', and, 'I-mfa', '(', inhibitor, of, 'MyoD', family, 'a),']), verbo([interacted]), complemento([in, vivo, with, 'LANA', through, their, 'C-terminal', 'I-mfa', domains])]). relacion([sujeto(['This', interaction, affected, the, intracellular, localization, of, 'HIC,']), verbo([inhibited]), complemento([the, 'LANA-dependent', transactivation, of, a, 'beta-catenin-regulated', reporter, 'construct,', and, decreased, the, level, of, the, 'LANA'])]). relacion([sujeto(['These', data]), verbo([reveal]), complemento([for, the, first, time, that, 'I-mfa', domain, proteins, interact, with, 'LANA', and, negatively, regulate, 'LANA-mediated', activation, of, 'Wnt', 'signaling-dependent', transcription, by, inhibiting, the, formation, of, the, 'LANA'])]). relacion([sujeto(['Human', 'I-mfa', domain, containing, protein, '(', 'HIC)', differentially]), verbo([regulates]), complemento([transcription, from, viral, promoters])]). relacion([sujeto(['Studies', exploring, 'HIC', function, in, mammalian, cells, used, ectopically]), verbo([expressed]), complemento(['HIC', due, to, undetected, endogenous, 'HIC', protein])]). relacion([sujeto(['The', 'HIC', mRNA, 'UTRs', reduce, the, expression, of, 'HIC', or, of, a, reporter, 'protein:', 'The', 'HIC', 3, '\'', -, 'UTR']), verbo([decreases]), complemento([both, 'HIC', and, reporter, mRNA, 'levels,', whereas, upstream, open, reading, frames, located, in, the, 5, '\'', -, 'UTR', repress, the, translation, of, 'HIC', or, of, the, reporter, protein])]). relacion([sujeto(['In', 'addition,', ectopically]), verbo([expressed]), complemento(['HIC', protein, is, degraded, by, the, 'proteasome,', with, a, 'half-life', of, approximately, 1, 'h,', suggesting, that, upon, 'activation,', 'HIC', expression, in, cells, may, be, transient])]). relacion([sujeto(['The', strict, regulation, of, 'HIC', expression, at, the, levels, of, mRNA, 'stability,', translation, efficiency, and, protein, stability]), verbo([suggests]), complemento([that, expression, of, the, 'HIC', protein, and, its, involvement, in, the, various, pathways, is, required, only, under, specific, cellular, conditions])]). relacion([sujeto(['Although', the, precise, function, of, 'HIC', remains, to, be, 'clarified,', the, association, of, the, 'HIC', gene, locus, with, myeloid, 'neoplasms,', its, interactions, with, lymphotropic, viruses, such, as, 'EBV,', 'HIV-1', and, 'HTLV-1', and, its, expression, in, immune, tissues]), verbo([suggest]), complemento([that, 'HIC', might, have, a, modulatory, role, in, immune, cells])]). relacion([sujeto(['To', further, characterise, the, 'HIC', functional, relationship, with, the, immune, 'system,', we, sought, to, analyse, the, 'HIC', gene, expression, profile, in, immune, cells, and, to, determine, if, immunomodulatory, 'cytokines,', such, as, interleukin, '(', 'IL)-2,', could]), verbo([regulate]), complemento([the, expression, of, 'HIC', mRNA])]). relacion([sujeto(['Relative', quantitative, 'real-time', 'RT-PCR', revealed, that, 'HIC', mRNA, is, highly]), verbo([expressed]), complemento([in, 'PBMCs', and, in, various, hematopoietic, cell, lines])]). relacion([sujeto(['Addition', of, cycloheximide, indicated, that, the, 'IL-2', effects, were, independent, of, de, novo, protein, synthesis, and, that, the, 'HIC', gene, is, a, direct]), verbo([target]), complemento([of, 'IL-2'])]). relacion([sujeto(['Two', cell, lines, '(', 'Jurkat', and, 'BJAB)', displayed, a, distinct]), verbo([loss]), complemento([in, 'HIC', gene, expression])]). relacion([sujeto(['Overall,', this]), verbo([report]), complemento([provides, new, insights, for, a, putative, role, of, 'HIC', in, the, modulation, of, immune, and, inflammatory, responses, 'and/or', hematological, malignancies])]). relacion([sujeto(['Nuclear', localization, of, 'N', is, 'non-essential', for, 'PRRSV', replication, in, cultured, cells, but]), verbo([has]), complemento([been, shown, to, modulate, the, pathogenesis, of, virus, in, 'pigs,', suggesting, that, 'N', plays, an, accessory, role, in, the, nucleus, during, infection])]). relacion([sujeto(['The', porcine, homolog, of, 'HIC', is, universally]), verbo([expressed]), complemento([in, pig, tissues, including, alveolar, macrophages])]). relacion([sujeto(['It']), verbo([has]), complemento([been, reported, that, the, human, 'I-mfa', '(', inhibitor, of, 'MyoD', family, 'a)', 'domain-containing', protein, '(', 'HIC)', interacts, with, 'P-TEFb', and, that, expression, of, 'HIC', cDNA, stimulates, 'P-TEFb-dependent', transcription])]). relacion([sujeto(['In', transient, 'transfections,', overexpression, of, 'HIC', 3, '\'', 'UTR']), verbo([stimulates]), complemento([transgene, expression, in, several, mammalian, cell, lines, and, significantly, increases, the, production, of, human, erythropoietin, and, 'interferon-gamma', in, 'Chinese', hamster, ovary, '(', 'CHO)', cells])]). relacion([sujeto(['This', is, the, first]), verbo([report]), complemento([that, demonstrates, the, improvement, of, expression, of, biopharmaceutical, proteins, by, overexpressing, a, 'non-coding', 3, '\'', 'UTR', in, 'CHO', cells])]). relacion([sujeto(['The', phenotypes, of, the, 'Scnm1Delta3-5', mutant, confirm, the, role, of, this, splice, factor, in, processing, the, 'Scn8a(medJ)', transcript, and]), verbo([provide]), complemento([a, new, allele, of, greater, severity, for, future, studies])]). relacion([sujeto(['The', bHLH, transcription, factor, 'Hand1', is, essential, for, placentation, and, cardiac, morphogenesis, but, how, its, developmental, activity, is]), verbo([regulated]), complemento([is, largely, unknown])]). relacion([sujeto(['We', recently, showed, that, 'Hand1', is, sequestered, in, the, nucleoli, of, rodent, trophoblast, stem, '(', 'TS)', cells, by, the, 'I-mfa', 'domain-containing', protein, 'HICp40', and, that, this, is]), verbo([associated]), complemento([with, their, proliferation, and, continuing, 'self-renewal'])]). relacion([sujeto(['However', when, these, cells, commit, to, differentiate, into, trophoblast, giant, '(', 'TG)', 'cells,', 'Hand1', is]), verbo([phosphorylated]), complemento([by, the, 'polo-like', kinase, 'Plk4', '(', 'Sak)', and, released, into, the, nucleus, to, activate, downstream, target, genes])]). relacion([sujeto(['This', event, underlies, the]), verbo([release]), complemento([of, 'Hand1', from, the, nucleolus, and, represents, the, '\'', molecular, 'switch\'', that, promotes, mitotic, cell, cycle, exit, and, the, onset, of, endoreduplication])]). relacion([sujeto(['It', is]), verbo([recruited]), complemento([to, 'HIV', transcription, complexes, by, the, viral, transactivator, 'Tat,', and, to, cellular, transcription, complexes, by, a, plethora, of, transcription, factors])]). relacion([sujeto(['P-TEFb', activity, is, negatively]), verbo([regulated]), complemento([by, sequestration, in, a, complex, with, the, 'HEXIM', proteins, and, 7, 'SK', 'RNA'])]). relacion([sujeto(['The', mechanism, of, 'P-TEFb']), verbo([release]), complemento([from, the, inhibitory, complex, is, not, known])]). relacion([sujeto(['We']), verbo([report]), complemento([that, 'P-TEFb-dependent', transcription, from, the, 'HIV', promoter, can, be, stimulated, by, the, mRNA, encoding, 'HIC,', the, human, 'I-mfa', 'domain-containing', protein])]). relacion([sujeto(['A', 314, -, nucleotide, sequence, near, the, 3, '\'', end, of, 'HIC', mRNA]), verbo([has]), complemento([full, activity, and, contains, a, predicted, structure, resembling, the, 3, '\'', -, terminal, hairpin, of, 7, 'SK', that, is, critical, for, 'P-TEFb', binding])]). relacion([sujeto(['This', represents, the, first, example, of, a, cellular, mRNA, that, can]), verbo([regulate]), complemento([transcription, via, 'P-TEFb'])]). relacion([sujeto(['Our', findings, offer, a, rationale, for, 7, 'SK', being, an, 'RNA', transcriptional, regulator, and]), verbo([suggest]), complemento([a, practical, means, for, enhancing, gene, expression])]). relacion([sujeto(['Positive', transcription, elongation, factor, b, '(', 'P-TEFb)', 'complexes,', composed, of, 'cyclin-dependent', kinase, 9, '(', 'CDK9)', and, cyclin, 'T1', or, 'T2,', are, engaged, by, many, cellular, transcription, regulators, that]), verbo([activate]), complemento([or, inhibit, transcription, from, specific, promoters])]). relacion([sujeto(['The', related, 'I-mfa', '(', inhibitor, of, 'MyoD', family, 'a)', and, 'HIC', '(', human, 'I-mfa-domain-containing)', proteins, function, in, myogenic, differentiation, and, embryonic, development, by]), verbo([participating]), complemento([in, the, 'Wnt', signaling, pathway])]). relacion([sujeto(['We']), verbo([report]), complemento([that, 'I-mfa', is, a, novel, regulator, of, 'P-TEFb'])]). relacion([sujeto(['Both', 'HIC', and, 'I-mfa']), verbo([interact]), complemento([through, their, homologous, 'I-mfa', domains, with, cyclin, 'T1', and, 'T2', at, two, binding, sites])]). relacion([sujeto(['One', site, is, the, regulatory, 'histidine-rich', domain, that]), verbo([interacts]), complemento([with, 'CDK9', substrates, including, 'RNA', polymerase, 'II'])]). relacion([sujeto(['The', second, site, contains, a, lysine, and, 'arginine-rich', motif, that, is, highly]), verbo([conserved]), complemento([between, the, two, 'T', cyclins])]). relacion([sujeto(['This', site, overlaps, and, includes, the, previously, identified, 'Tat/TAR', recognition, motif, of, cyclin, 'T1']), verbo([required]), complemento([for, activation, of, human, immunodeficiency, virus, type, 1, '(', 'HIV-1)', transcription])]). relacion([sujeto(['Their', 'I-mfa', domains, also]), verbo([bind]), complemento([the, activation, domain, of, 'HIV-1', 'Tat', and, inhibit, 'Tat-', and, 'P-TEFb-dependent', transcription, from, the, 'HIV-1', promoter])]). relacion([sujeto(['Our', findings, link, 'I-mfa', and, 'HIC', to, viral, 'replication,', and]), verbo([suggest]), complemento([that, 'P-TEFb', is, modulated, in, the, 'Wnt', signaling, pathway])]). relacion([sujeto(['We']), verbo([have]), complemento([previously, shown, that, 'beta-catenin', interacts, with, a, transcription, suppressor, 'I-mfa', 'and,', through, this, 'interaction,', canonical, 'Wnt', signaling, could, relieve, 'I-mfa-mediated', suppression, of, myogenic, regulatory, factors, '(', 'MRFs)'])]). relacion([sujeto(['In', this, 'study,', we]), verbo([found]), complemento(['that,', based, on, this, 'interaction,', 'I-mfa-mediated', suppression, of, the, 'Wnt', transcription, factor, 'T-cell', 'factor/lymphoid', enhancing, 'factor-1', '(', 'TCF/LEF-1)', can, also, be, relieved])]). relacion([sujeto(['Our', work, showed, that, knocking, down, endogenous, 'I-mfa', expression, mimics, canonical, 'Wnt', treatment, by]), verbo([inducing]), complemento([myogenesis, and, increasing, 'Wnt', reporter, gene, 'activity,', endogenous, 'Wnt', target, gene, expression, and, expression, of, 'MRFs', in, 'P19', cells])]). relacion([sujeto(['In', 'addition,', we]), verbo([found]), complemento([that, 'beta-catenin', could, compete, with, 'I-mfa', for, binding, to, 'LEF-1', and, relieve, the, inhibitory, effects, of, 'I-mfa', in, overexpression, systems])]). relacion([sujeto(['Furthermore,', canonical, 'Wnt', was, able, to, reduce, the, levels, of, endogenous, 'I-mfa']), verbo([associated]), complemento([with, 'LEF-1,', while, increasing, that, of, 'I-mfa', associated, with, 'beta-catenin'])]). relacion([sujeto(['All', of, the, evidence, supports, a, conclusion, that, 'I-mfa', can]), verbo([suppress]), complemento([myogenesis, by, inhibiting, 'TCF/LEF-1', and, that, canonical, 'Wnt', signaling, may, relieve, the, suppression, through, elevating, 'beta-catenin', 'levels,', which, in, turn, relieve, 'I-mfa-mediated', suppression])]). relacion([sujeto(['We', studied, monosomy, and, deletions, of, chromosome, 7, in, 170, patients, with, myeloid, disorders, and, we, identified, a, minimal, region, of]), verbo([loss]), complemento([in, 7, q31])]). relacion([sujeto(['No', mutations, were]), verbo([found]), complemento([in, the, coding, region, of, this, gene])]). relacion([sujeto(['Mutation', of, the]), verbo([nuclear]), complemento([receptor, peroxisome, 'proliferator-activated', receptor, 'beta/delta', '(', 'PPARbeta/delta)', severely, affects, placenta, 'development,', leading, to, embryonic, death, at, embryonic, day, 9.5, '(', 'E9'])]). relacion([sujeto(['While', very, little, is, known, at, present, about, the, pathway, governed, by, 'PPARbeta/delta', in, the, developing, 'placenta,', this, paper, demonstrates, that, the, main, alteration, of, the, placenta, of, 'PPARbeta/delta-null', embryos, is]), verbo([found]), complemento([in, the, giant, cell, layer])]). relacion([sujeto(['Conversely,', exposure, of, 'Rcho-1', cells, to, a, 'PPARbeta/delta', agonist]), verbo([triggers]), complemento([a, massive, differentiation, via, increased, expression, of, 3, -, 'phosphoinositide-dependent', kinase, 1, and, 'integrin-linked', kinase, and, subsequent, phosphorylation, of, 'Akt'])]). relacion([sujeto(['In', addition, to, this, phosphatidylinositol, 3, -, 'kinase/Akt', main, 'pathway,', 'PPARbeta/delta', also]), verbo([induced]), complemento([giant, cell, differentiation, via, increased, expression, of, 'I-mfa,', an, inhibitor, of, 'Mash-2', activity])]). relacion([sujeto([5, is, accompanied, by, a, 'PPARbeta/delta-dependent', accumulation, of, lipid, droplets, and, an]), verbo([increased]), complemento([expression, of, the, adipose, 'differentiation-related', protein, '(', also, called, 'adipophilin),', which, may, participate, to, lipid, metabolism, 'and/or', steroidogenesis])]). relacion([sujeto(['mPem,', a, homeobox, 'gene,', is]), verbo([expressed]), complemento([in, a, time, and, stage, specific, manner, during, murine, ontogeny])]). relacion([sujeto(['Pem', transcripts, are, abundant, in, 7, -, and, 8, -, day, mouse, 'embryos,', but]), verbo([decrease]), complemento([precipitously, thereafter])]). relacion([sujeto([3, proteins, were]), verbo([found]), complemento([interacting, with, mPem, protein])]). relacion([sujeto(['The', interaction, between, mPem, and, 'Mdfic']), verbo([suggested]), complemento([they, maybe, form, the, transcriptional, regulator, complex, to, regulate, embryo, differentiation])]). relacion([sujeto(['We']), verbo([found]), complemento([that, 'beta-catenin', interacted, with, 'I-mfa', and, that, the, interaction, was, enhanced, by, 'Wnt3a'])]). relacion([sujeto(['In', 'addition,', we]), verbo([found]), complemento([that, the, interaction, between, 'beta-catenin', and, 'I-mfa', was, able, to, attenuate, the, interaction, of, 'I-mfa', with, 'MRFs,', relieve, 'I-mfa-mediated', suppression, of, the, transcriptional, activity, and, cytosolic, sequestration, of, 'MRFs,', and, initiate, myogenesis, in, a, 'P19', myogenic, model, system, that, expresses, exogenous, myogenin])]). relacion([sujeto(['This', work]), verbo([reveals]), complemento([a, mechanism, for, the, regulation, of, 'MRFs', during, myogenesis, by, elucidating, a, 'beta-catenin-mediated,', but, lymphoid, enhancing, 'factor-1/T', cell, factor, 'independent,', mechanism, in, regulation, of, myogenic, fate, specification, and, differentiation, of, 'P19', mouse, stem, cells])]). relacion([sujeto(['The', primary, function, of, the, 'HIV-1', regulatory, protein, 'Tat,', activation, of, transcription, from, the, viral, 'LTR,', is, highly]), verbo([regulated]), complemento([by, complex, interactions, between, 'Tat', and, a, number, of, host, cell, proteins])]). relacion([sujeto(['Tat']), verbo([nuclear]), complemento(['import,', a, process, mediated, by, importin, 'beta,', is, a, prerequisite, for, its, activity])]). relacion([sujeto(['Here,', we]), verbo([report]), complemento([and, characterize, the, interaction, of, the, human, inhibitor, of, 'MyoD', family, 'domain-containing', protein, '(', 'I-mfa),', 'HIC,', with, 'Tat', at, a, biochemical, and, a, functional, level])]). relacion([sujeto(['This', interaction, was, shown, to, occur, in, vivo, and, in, vitro, and, to]), verbo([involve]), complemento([the, nuclear, localization, signal, and, the, transactivation, responsive, 'element-binding', domains, of, 'Tat', and, the, 'I-mfa', domain, of, 'HIC'])]). relacion([sujeto(['Villous', stromal, cells, in, situ, and, cultivated, placental, fibroblasts, also, produced, 'I-mfa', and, 'Stra13', but, failed, to]), verbo([express]), complemento(['Hash-2'])]). relacion([sujeto(['The', widely]), verbo([expressed]), complemento([class, 'A', 'proteins,', 'E12/E47', were, absent, from, all, placental, cell, types, while, 'ITF-2', was, restricted, to, placental, stromal, cells, of, early, and, late, gestation])]). relacion([sujeto(['The', data]), verbo([suggest]), complemento([that, a, complex, interplay, of, activators, '(', 'Hash-2,', 'HEB)', and, repressors, '(', 'Stra13,', 'I-mfa)', could, be, involved, in, extravillous, trophoblast, differentiation, whereas, downregulation, of, 'Id', proteins, could, play, a, role, in, syncytialisation])]). relacion([sujeto(['We']), verbo([have]), complemento([determined, that, 'XIC,', a, 'Xenopus', 'I-mfa', domain, protein, that, regulates, 'Tcf3', 'binding,', is, required, for, dorsoaxial, development, and, specifically, for, 'Siamois', activity, in, establishing, the, dorsal, organizer])]). relacion([sujeto(['In', 'loss-of-function', 'studies,', we]), verbo([found]), complemento([that, embryos, injected, with, a, morpholino, to, 'XIC', mRNA, '(', 'XIC', 'morphpolino)', are, missing, head, 'structures,', neural, 'tube,', 'notochord,', and, paraxial, mesoderm, as, well, as, 'NCAM', and, 'XMyoD', expression])]). relacion([sujeto(['Ectopic', axis, formation]), verbo([induced]), complemento([by, 'Siamois', is, repressed, by, injection, of, the, 'XIC', morpholino, and, further, repressed, by, coinjection, of, 'beta-catenin', or, a, constitutively, active, 'Tcf3/HMG/G4A', fusion])]). relacion([sujeto(['Activation', of, reporters, driven, by, the, 'Siamois-responsive', proximal, element, of, the, goosecoid, promoter, is]), verbo([inhibited]), complemento([in, the, presence, of, the, morpholino, and, can, be, rescued, by, murine, 'I-mfa', and, by, a, 'dominant-negative', 'Tcf3'])]). relacion([sujeto(['The', data, indicate, a, role, for, 'XIC', in, limiting, 'Tcf3-dependent', repression, of, 'Siamois', activities, that, are]), verbo([required]), complemento([for, goosecoid, transcription, and, for, dorsal, organizer, formation])]). relacion([sujeto(['In', addition, to, the, interaction, previously, identified, with, cellular, 'Notch,', it, was, determined, that, 'RK-BARF0', also]), verbo([bound]), complemento([cellular, human, 'I-mfa', 'domain-containing', protein, '(', 'HIC),', 'epithelin,', and, scramblase])]). relacion([sujeto(['An', interaction, between, 'RK-BARF0', and, 'Notch', or, epithelin]), verbo([induced]), complemento(['proteasome-dependent', degradation, of, 'Notch', and, epithelin, but, not, of, 'HIC', or, scramblase])]). relacion([sujeto(['These', data]), verbo([suggest]), complemento([that, while, 'RK-BARF0', may, have, important, cellular, functions, during, 'EBV', 'infection,', and, while, the, phenotype, of, 'EBV-positive', cells, suggest, its, 'expression,', 'RK-BARF0', levels, may, be, too, low, to, detect])]). relacion([sujeto(['Previous', studies]), verbo([have]), complemento([shown, that, 'Zic1,', 'Zic2,', and, 'Zic3', can, act, as, transcriptional, 'regulators,', and, that, their, functions, are, repressed, by, 'I-mfa,', which, has, been, identified, as, a, repressor, for, basic, 'helix-loop-helix-type', transcriptional, factors])]). relacion([sujeto(['However,', 'Zic4/Zic5', did, not, exhibit, any, significant, transcriptional, activation, ability, nor, they]), verbo([bind]), complemento([to, 'I-mfa', differently, from, 'Zic1/Zic2/Zic3'])]). relacion([sujeto(['The']), verbo([nuclear]), complemento([localization, of, 'Zic4/Zic5', was, not, affected, by, the, presence, of, the, 'I-mfa', 'protein,', whereas, the, 'Zic1/Zic2/Zic3', proteins, were, translocated, to, the, cytoplasmic, compartment, in, the, presence, of, 'I-mfa'])]). relacion([sujeto(['The', difference, may, be, attributable, to, the, dissimilarity, of, the, 'N-terminal', region, between, the, 'Zic1/Zic2/Zic3', and, 'Zic4/Zic5', 'proteins,', since, the]), verbo([binding]), complemento([of, the, 'Zic1/Zic2/Zic3', proteins, to, 'I-mfa', occurs, through, their, 'N-terminal', regions])]). relacion([sujeto(['Here', we, mapped, the, transcriptional, regulatory, domains, in, 'Zic2', protein, and, identified, a, protein, which, specifically]), verbo([binds]), complemento([to, one, of, them])]). relacion([sujeto(['A', search, for, proteins]), verbo([binding]), complemento([to, the, amino, terminal, domain, of, 'Zic2', revealed, that, inhibitor, of, 'MyoD', family, '(', 'I-mfa)', 'protein,', which, has, been, identified, as, a, repressor, of, myogenic, 'helix-loop-helix', class, transcription, 'factors,', can, physically, interact, with, the, amino, terminal, domain])]). relacion([sujeto(['When', 'Zic1-3', and, 'I-mfa', proteins, were, 'co-expressed', in, cultured, 'cells,']), verbo([nuclear]), complemento([import, of, the, 'Zic', proteins, was, inhibited])]). relacion([sujeto(['Consequently,', 'I-mfa']), verbo([inhibited]), complemento([transcriptional, activation, by, the, 'Zic', proteins, in, cultured, cells])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, the, physical, and, functional, interaction, between, 'Zic', and, 'I-mfa', proteins, can, play, a, role, in, the, vertebrate, development])]). relacion([sujeto(['Depletion', of, intracellular, 'Ca2+', stores]), verbo([leads]), complemento([to, the, activation, of, 'Ca2+', inflow, through, 'store-operated', 'Ca2+', channels])]). relacion([sujeto(['Although', the, identity, of, these, channels, is, 'unknown,', there, is, considerable, evidence, that, the, transient, receptor, potential, channel, 1, '(', 'TRPC1)']), verbo([participates]), complemento([in, the, formation, of, these, channels])]). relacion([sujeto(['We', show, that, 'TRPC1', physically]), verbo([interacts]), complemento([with, the, 'a-isoform', of, the, inhibitor, of, the, myogenic, family, '(', 'I-mfa),', a, known, inhibitor, of, basic, 'helix-loop-helix', transcription, 'factors,', in, vitro, and, in, vivo])]). relacion([sujeto(['The', interaction, is]), verbo([mediated]), complemento([by, the, 'C-terminal', cytoplasmic, tail, of, 'TRPC1', and, the, 'C-terminal', 'cysteine-rich', domain, of, 'I-mfa'])]). relacion([sujeto(['Using', the, whole, cell, configuration, of, the, patch, clamp, 'technique,', we, show, that, ectopic, expression, of, 'I-mfa', in, 'CHO-K1', cells, reduces, native, 'store-activated', 'Ca2+', 'currents,', whereas, 'knock-down', of, endogenous, 'I-mfa', in, 'A431', cells, by, 'RNA', interference]), verbo([enhances]), complemento([these, currents])]). relacion([sujeto(['Finally,', cell, dialysis, with, a, monoclonal, antibody, specific, to, 'TRPC1', results, in, the, suppression, of, 'store-activated', conductance, in, cells, lacking, 'I-mfa,', but, not, in, 'I-mfa']), verbo([expressing]), complemento([cells])]). relacion([sujeto(['We', propose, that, 'I-mfa', functions, as, a, molecular, switch, to]), verbo([suppress]), complemento([the, store, dependence, of, 'TRPC1'])]). relacion([sujeto(['HIC']), verbo([has]), complemento([been, reported, to, modulate, expression, from, both, cellular, and, viral, promoters, via, its, 'C-terminal', 'cysteine-rich', 'domain,', which, is, similar, to, the, inhibitor, of, 'MyoD', family, a, '(', 'I-mfa)', protein])]). relacion([sujeto(['We', show, that, 'HIC']), verbo([binds]), complemento([cyclin, 'T1', in, yeast, and, mammalian, cells, and, that, it, interacts, with, intact, 'P-TEFb', in, mammalian, cell, extracts])]). relacion([sujeto(['The', interaction]), verbo([involves]), complemento([the, 'I-mfa', domain, of, 'HIC', and, the, regulatory, 'histidine-rich', region, of, cyclin, 'T1'])]). relacion([sujeto(['HIC', also]), verbo([binds]), complemento(['Tat', via, its, 'I-mfa', 'domain,', although, the, sequence, requirements, are, different])]). relacion([sujeto(['HIC', colocalizes, with, cyclin, 'T1', in]), verbo([nuclear]), complemento([speckle, regions, and, with, 'Tat', in, the, nucleolus])]). relacion([sujeto(['Expression', of, the, 'HIC', cDNA]), verbo([modulates]), complemento(['Tat', transactivation, of, the, 'HIV-1', long, terminal, repeat, '(', 'LTR)', in, a, cell, 'type-specific', fashion])]). relacion([sujeto(['It', is, mildly, inhibitory, in, 'CEM', cells, but]), verbo([stimulates]), complemento([gene, expression, in, 'HeLa,', 'COS,', and, 'NIH', 3, 'T3', cells])]). relacion([sujeto(['The', isolated, 'I-mfa', domain]), verbo([acts]), complemento([as, a, dominant, negative, inhibitor])]). relacion([sujeto(['Activation', of, the, 'HIV-1', 'LTR', by, 'HIC', in, 'NIH', 3, 'T3', cells, occurs, at, the, 'RNA', level, and, is]), verbo([mediated]), complemento([by, direct, interactions, with, 'P-TEFb'])]). relacion([sujeto(['We', describe, here, a, new, family, of, proteins, characterized, by, a, particular, 'cysteine-rich', 'carboxy-terminal', domain, and]), verbo([involved]), complemento([in, gene, expression, regulation])]). relacion([sujeto(['I-mfa,', by]), verbo([interacting]), complemento([with, 'MyoD', family, 'members,', represses, both, transcriptional, activation, and, myogenesis, mediated, by, these, factors])]). relacion([sujeto(['HIC', two, 'isoforms,', 'HIC', p40, and, 'HIC', 'p32,', are]), verbo([involved]), complemento([in, the, positive, regulation, of, 'Tax-mediated', 'HTLV-I', '(', human, 'T-cell', leukemia, virus, type, 1, ')', promoter, activation, and, in, the, negative, regulation, of, 'Tat-mediated', 'HIV-1', '(', human, immunodeficiency, virus, type, 1, ')', promoter, transcription])]). relacion([sujeto(['The', common, 'carboxy-terminal', region, of, 'HIC', p40, and, 'HIC', 'p32,', which, is, clearly]), verbo([involved]), complemento([in, these, 'regulations,', shares, 77, '%', homology, with, the, 'carboxy-terminal', domain, of, 'I-mfa'])]). relacion([sujeto(['This']), verbo([suggests]), complemento([that, 'I-mfa,', 'HIC', p40, and, 'HIC', p32, are, part, of, a, new, family, of, proteins, involved, in, gene, expression, regulation, and, characterized, by, a, specific, 'cysteine-rich', 'carboxy-terminal', domain])]). relacion([sujeto(['Effectively,', a, mechanism, of, protein, sequestration, in, a, particular, 'compartment,', cytoplasm, or, 'nucleolus,', could, be]), verbo([involved]), complemento([in, their, 'function,', as, it, is, the, case, for, many, other, proteins])]). relacion([sujeto(['I-mfa']), verbo([has]), complemento([been, identified, as, an, inhibitor, of, myogenic, basic, 'helix-loop-helix', transcription, 'factors,', and, a, related, human, 'I-mfa', 'domain-containing', protein, '(', 'HIC)', also, has, been, identified, as, a, protein, that, regulates, 'Tat-', and, 'Tax-mediated', expression, of, viral, promoters])]). relacion([sujeto(['HIC', and, 'I-mfa', represent, a, family, of, proteins, that, share, a, highly]), verbo([conserved]), complemento(['cysteine-rich', 'domain,', termed, the, 'I-mfa', domain])]). relacion([sujeto(['We', show, here, that, both, 'I-mfa', domain, 'proteins,', 'HIC', and, 'I-mfa,']), verbo([interacted]), complemento([in, vivo, with, the, 'Axin', complex, through, their, 'C-terminal', 'I-mfa', domains])]). relacion([sujeto(['This', interaction]), verbo([inhibited]), complemento(['Axin-mediated', downregulation, of, free, levels, of, cytosolic, 'beta-catenin'])]). relacion([sujeto(['I-mfa', and, 'HIC', also, both, directly]), verbo([interacted]), complemento([with, lymphocyte, enhancer, factor, '(', 'LEF);', 'however,', 'I-mfa', but, not, 'HIC', significantly, inhibited, reporter, constructs, regulated, by, 'beta-catenin'])]). relacion([sujeto(['The', overexpression, of, 'HIC', but, not, 'I-mfa']), verbo([decreased]), complemento([the, inhibitory, effects, of, 'Axin', on, 'beta-catenin-regulated', reporter, 'constructs,', while, both, 'HIC', and, 'I-mfa', decreased, 'Axin-mediated', 'c-Jun', 'N-terminal', kinase, '(', 'JNK)', activation])]). relacion([sujeto(['These', data]), verbo([reveal]), complemento([for, the, first, time, that, 'I-mfa', domain, proteins, interact, with, the, 'Axin', complex, and, affect, 'Axin', regulation, of, both, the, 'Wnt', and, the, 'JNK', activation, pathways])]). relacion([sujeto(['To', identify, genes, that, are, rapidly]), verbo([induced]), complemento([by, gonadotropin, in, the, immature, rat, 'ovary,', ovarian, genes, were, screened, by, a, subtraction, cloning, procedure])]). relacion([sujeto(['RNA', analyses, revealed, that, these, mRNAs, were, rapidly, and, temporarily]), verbo([induced]), complemento([by, gonadotropins, in, the, rat, testis, as, well, as, in, the, ovary])]). relacion([sujeto(['In', situ, hybridization, study, revealed, that, expression, of, 'GIOT1', was]), verbo([induced]), complemento([in, theca, interna, cells, in, the, ovary, and, 'Leydig', cells, in, the, testis])]). relacion([sujeto(['Interestingly,', the, gene, expression, of, 'GIOT1', is, restricted, to, the, 'pituitary,', 'adrenal,', 'testis,', and, 'ovary,', while, 'GIOT2', gene, is]), verbo([expressed]), complemento([ubiquitously])]). relacion([sujeto(['A', 'GAL4-based', yeast, 'two-hybrid', system, was, also, used, to, identify, proteins, that]), verbo([interact]), complemento([with, the, rat, 'GIOT1'])]). relacion([sujeto(['Our', data, strongly]), verbo([suggest]), complemento([that, 'GIOT1', may, function, as, a, novel, transcriptional, repressor, by, working, with, rat, homologs, of, human, 'I-mfa', domain, containing, protein, and, transcriptional, intermediary, factor, 1, beta, proteins, and, may, play, a, significant, role, at, the, transcription, level, in, the, folliculogenesis])]). relacion([sujeto(['I-mfa', '(', inhibitor, of, the, 'MyoD', 'family)', is, a, transcription, modulator, that]), verbo([binds]), complemento([to, and, suppresses, the, transcriptional, activity, of, 'MyoD', family, members])]). relacion([sujeto(['I-mfa', transcripts, are]), verbo([expressed]), complemento([in, 'sclerotome,', suggesting, a, role, of, 'I-mfa', in, skeletogenesis])]). relacion([sujeto(['We']), verbo([found]), complemento([that, 'I-mfa', is, expressed, at, a, low, level, in, an, 'osteoblast-like', cell, 'line,', 'MC3T3E1,', and, a, pluripotent, differentiation, 'modulator,', 1, ',', 25, -, dihydroxyvitamin, 'D(3),', specifically, enhanced, 'I-mfa', mRNA, expression])]). relacion([sujeto(['This', effect, was, completely, blocked, by, the, presence, of, an, 'RNA', polymerase, 'inhibitor,', but, not, by, a, protein, synthesis, 'inhibitor,']), verbo([suggesting]), complemento([that, 1, ',', 25, -, dihydroxyvitamin, 'D(3)', upregulates, transcription, of, the, 'I-mfa', gene, without, requirement, for, new, protein, synthesis])]). relacion([sujeto(['Western', blot, analysis, indicated, that, 1, ',', 25, -, dihydroxyvitamin, 'D(3)']), verbo([increased]), complemento([the, 'I-mfa', protein, levels, severalfold, in, 'MC3T3E1', cells])]). relacion([sujeto([8, cells, and, 1, ',', 25, -, dihydroxyvitamin, 'D(3)']), verbo([enhanced]), complemento(['I-mfa', expression, in, these, cells])]). relacion([sujeto(['These', data, indicate, that, 'I-mfa', is, a, novel, transcriptional, regulator, gene]), verbo([expressed]), complemento([in, osteoblasts, and, that, its, level, is, under, the, control, of, 1, ',', 25, -, dihydroxyvitamin, 'D(3)'])]). relacion([sujeto(['The', two, isoforms, show, different, subcellular, 'localization:', p32, is, distributed, throughout, the, cytoplasm, whereas, p40, can, be]), verbo([found]), complemento([both, in, the, cytoplasm, and, the, nucleolus])]). relacion([sujeto(['To', investigate, the, possibility, that, p40, contains, a, nucleolus]), verbo([targeting]), complemento([sequence, in, its, 'N-terminal', 'region,', 'COS', cells, were, transfected, with, an, eukaryotic, expression, vector, coding, for, green, fluorescent, protein, '(', 'GFP)', fused, to, the, p40, 'N', terminus])]). relacion([sujeto(['To']), verbo([find]), complemento([the, structural, motifs, required, for, nucleolar, localization, of, 'p40,', deletion, mutants, were, expressed, in, 'COS', cells, as, fusion, polypeptides, with, 'GFP'])]). relacion([sujeto(['We']), verbo([report]), complemento([here, the, characterization, of, a, novel, cellular, factor, sharing, homology, with, the, specific, 'cysteine-rich', 'C-terminal', domain, of, the, basic, 'helix-loop-helix', repressor, protein, 'I-mfa'])]). relacion([sujeto(['We', show, that, the, 'HIC', protein, isoforms, present, different, subcellular, 'localizations,', p32, being, mainly, distributed, throughout, the, 'cytoplasm,', whereas, p40, is]), verbo([targeted]), complemento([to, the, nucleolus])]). relacion([sujeto(['Moreover,', in, trying, to, understand, the, function, of, 'HIC,', we]), verbo([have]), complemento([found, that, both, isoforms, stimulate, in, 'T-cells', the, expression, of, a, luciferase, reporter, gene, driven, by, the, human, 'T-cell', leukemia, virus, type, 'I-long', terminal, repeat, in, the, presence, of, the, viral, transactivator, 'Tax'])]). relacion([sujeto(['We', demonstrate, by, mutagenesis, that, the, 'I-mfa-like', domain, of, 'HIC', is]), verbo([involved]), complemento([in, this, regulation])]). relacion([sujeto(['Finally,', we, also, show, that, 'HIC', is, able, to, 'down-regulate', the, luciferase, expression, from, the, human, immunodeficiency, virus, type, 1, -, long, terminal, repeat]), verbo([induced]), complemento([by, the, viral, transactivator, 'Tat'])]). relacion([sujeto(['From', these, 'results,', we, propose, that, 'HIC', and, 'I-mfa', represent, two, members, of, a, new, family, of, proteins]), verbo([regulating]), complemento([gene, expression, and, characterized, by, a, particular, 'cysteine-rich', 'C-terminal', domain])]). relacion([sujeto(['The', 'bHLH-repressor', protein, 'I-mfa']), verbo([binds]), complemento([to, 'MyoD', family, 'members,', inhibits, their, 'activity,', and, blocks, their, nuclear, import, and, binding, to, 'DNA'])]). relacion([sujeto(['In', situ, hybridization, analysis, demonstrated, that, mouse, 'I-mfa', was, highly]), verbo([expressed]), complemento([in, extraembryonic, 'lineages,', in, the, 'sclerotome,', and, subsequently, within, mesenchymal, precursors, of, the, axial, and, appendicular, 'skeleton,', before, chondrogenesis, occurs])]). relacion([sujeto([5, ',']), verbo([associated]), complemento([with, a, placental, defect, and, a, markedly, reduced, number, of, trophoblast, giant, cells])]). relacion([sujeto(['Overexpression', of, 'I-mfa', in, rat, trophoblast, '(', 'Rcho-1)', stem, cells]), verbo([induced]), complemento([differentiation, into, trophoblast, giant, cells])]). relacion([sujeto(['I-mfa']), verbo([interacted]), complemento([with, the, bHLH, protein, 'Mash2,', a, negative, regulator, of, trophoblast, giant, cell, 'formation,', and, inhibited, its, transcriptional, activity, in, cell, culture])]). relacion([sujeto(['Our', results, indicate, that, 'I-mfa', plays, an, important, role, in, trophoblast, and, chondrogenic, differentiation, by, negatively]), verbo([regulating]), complemento([a, subset, of, 'lineage-restricted', bHLH, proteins])]). relacion([sujeto(['A', number, of, 'genes,', spanning, the, evolutionary, scale, from, yeast, to, 'mammals,', that, are]), verbo([involved]), complemento([in, spatial, and, temporal, patterning, during, development, contain, zinc, finger, and, homeodomain, motifs])]). relacion([sujeto(['One', such, zinc, 'finger/homeodomain', protein, is, 'Drosophila', 'Zfh-1,', a, member, of, the, zfh, family, of, 'Drosophila', 'genes,', which, is]), verbo([expressed]), complemento([in, muscle, precursors, and, is, critical, for, the, proper, development, of, muscle])]). relacion([sujeto(['We', show, that, 'ZEB']), verbo([binds]), complemento([to, a, subset, of, 'E', boxes, in, muscle, genes, and, functions, by, actively, repressing, transcription])]). relacion([sujeto(['One']), verbo([target]), complemento([of, this, repression, is, the, members, of, the, 'MEF-2', 'family,', which, synergize, with, proteins, of, the, myogenic, basic, 'helix-loop-helix', family, '(', 'bHLH)', '(', 'myoD,', 'myf-5,', myogenin, and, 'MRF-4)', to, induce, myogenic, differentiation])]). relacion([sujeto(['As', muscle, differentiation, 'proceeds,', myogenic, bHLH, proteins, accumulate, to, levels, sufficient, to, displace, 'ZEB', from, the, 'E', 'boxes,']), verbo([releasing]), complemento([the, repression, and, allowing, bHLH, proteins, to, further, activate, transcription])]). relacion([sujeto(['This', mechanism, of, active, transcriptional, repression, distinguishes, 'ZEB', from, other, negative, regulators, of, myogenesis, '(', 'Id,', 'Twist', and, 'I-mfa)', that]), verbo([inhibit]), complemento([muscle, differentiation, by, simply, binding, and, inactivating, myogenic, factors])]). relacion([sujeto(['The', relative, affinity, of, 'ZEB', versus, myogenic, bHLH, proteins, varies, for, 'E', boxes, in, different, genes, such, that, 'ZEB', would, be, displaced, from, different, genes, at, distinct, times, as, myogenic, bHLH, proteins, accumulate, during, 'myogenesis,', thus]), verbo([providing]), complemento([a, mechanism, to, regulate, temporal, order, of, gene, expression])]). relacion([sujeto(['However,', these, approaches]), verbo([require]), complemento([the, use, of, sophisticated, and, expensive, 'serum-free', medium, supplemented, with, epithelial, growth, factor, '(', 'EGF),', 'Wnt', agonist, '(', 'R-spondin', 1, ')', ',', and, bone, morphogenetic, protein, inhibitor, '(', 'Noggin)', in, high, concentrations])]). relacion([sujeto(['They']), verbo([have]), complemento([the, appearance, of, empty, spheres, and, comprise, cells, expressing, cytokeratin, '(', an, epithelial, cell, 'marker),', villin, '(', a, marker, of, 'enterocytes),', and, 'Sox-9', '(', a, transcription, factor, characteristic, of, progenitors, and, stem, cells, of, intestinal, 'crypts)'])]). relacion([sujeto(['With', chicken, embryonic, tissue, as, a, source, of, 'organoids,', prostaglandin, 'E2', is, as, effective, as, 'R-spondin', 1, and, 'Noggin', in]), verbo([promoting]), complemento([sustained, growth, and, survival, of, epithelial, spheroids])]). relacion([sujeto(['Transcription', factor, '(', 'TF)', signaling]), verbo([regulates]), complemento([gene, transcription, and, requires, a, complex, network, of, proteins])]). relacion([sujeto(['It']), verbo([has]), complemento([been, widely, appreciated, that, pioneer, 'factors,', such, as, 'FoxA1', and, 'GATA1,', play, an, important, role, in, opening, closed, chromatin, 'regions,', thereby, allowing, binding, of, a, secondary, factor])]). relacion([sujeto(['Under', this, 'view,', many, 'TFs', can]), verbo([act]), complemento([as, initiating, factors, for, chromatin, landscape, programming])]). relacion([sujeto(['Diamond', 'Blackfan', anemia, '(', 'DBA)', is, a, well, known, inherited, bone, marrow, failure, syndrome, mostly]), verbo([caused]), complemento([by, mutations, in, ribosomal, protein, '(', 'RP)', genes, but, also, rarely, in, the, hematopoietic, transcription, factor, 'gene,', &, 'lt;i>GATA1</i>,', or, &, 'lt;i>TSR2</i>,', a, ribosomal, protein, '(', 'Rps26)', chaperone, gene])]). relacion([sujeto(['About', 25, '%', of, patients]), verbo([have]), complemento([heterozygous, mutations, in, the, &, 'lt;i>RPS19</i>', 'gene,', which, leads, to, haploinsufficiency, of, 'Rps19', protein, in, most, cases])]). relacion([sujeto(['However,', some, &, 'lt;i>RPS19</i>', missense, mutations, appear, to]), verbo([act]), complemento([in, a, dominant, negative, fashion])]). relacion([sujeto(['DBA', typically]), verbo([leads]), complemento([to, a, hypoplastic, anemia, that, becomes, apparent, during, the, first, year, of, 'life,', and, standard, treatment, includes, steroids, or, red, blood, cell, 'transfusions,', each, modality, having, attendant, side, effects])]). relacion([sujeto(['DBA-mutant', 'embryonic,']), verbo([induced]), complemento(['pluripotent,', and, hematopoietic, stem, cells, exhibit, growth, abnormalities, that, can, be, corrected, by, 'DNA', gene, 'transfer,', suggesting, the, possibility, of, ex, vivo, autologous, gene, therapy])]). relacion([sujeto(['We']), verbo([have]), complemento([been, interested, in, the, application, of, 'Spliceosome', 'Mediated', mRNA, 'trans-splicing', '(', 'SMaRT)', technology, to, 'RNA', repair, of, 'DBA', stem, cells])]). relacion([sujeto(['Compared', with, gene, replacement, or, other, 'RNA', 're-programming', 'approaches,', the, 'RNA', 'trans-splicing', technology, offers, several, 'advantages:', 1, ')', it, obviates, the, need, to, deliver, the, entire, cDNA, of, a, normal, 'gene,', which, significantly, reduces, the, transgene, size, for, packaging, and, 'delivery;', 2, ')', expression, of, the, corrected, gene, is, completely, dependent, on, expression, of, the, endogenous, mutant, 'gene,', and, genes, with, large, and, complex, transcriptional, elements, can, be, repaired, in, situ, while, keeping, gene, expression, under, the, control, of, endogenous, regulatory, 'elements;', 3, ')', 'RNA', 'trans-splicing', utilizes, the, endogenous, spliceosome, that, exists, and, functions, in, all, types, of, 'cells;', 4, ')', 'RNA', 'trans-splicing', converts, mutant, transcripts, into, therapeutically, useful, 'mRNA,', and, 'thus,', may, be, capable, of, treating, disorders]), verbo([caused]), complemento([by, dominant, negative, mutations, such, as, in, 'DBA'])]). relacion([sujeto(['Transcription', factors, '(', 'TFs)', are, proteins, that]), verbo([bind]), complemento([to, specific, 'DNA', sequences, and, regulate, expression, of, genes])]). relacion([sujeto(['There', is, now]), verbo([increasing]), complemento([evidence, that, mutations, in, hematopoietic, 'TFs', are, an, important, underlying, cause, for, the, defects, in, platelet, 'production,', 'morphology,', and, function])]). relacion([sujeto(['These', 'TFs']), verbo([act]), complemento([in, a, combinatorial, manner, to, bind, 'sequence-specific', 'DNA', within, a, promoter, region, to, regulate, 'lineage-specific', gene, 'expression,', either, as, activators, or, as, repressors])]). relacion([sujeto(['TF', mutations]), verbo([induce]), complemento([rippling, downstream, effects, by, simultaneously, altering, the, expression, of, multiple, genes])]). relacion([sujeto(['Mutations']), verbo([involving]), complemento([these, 'TFs', affect, diverse, aspects, of, megakaryocyte, biology, and, platelet, production, and, 'function,', culminating, in, 'thrombocytopenia,', platelet, 'dysfunction,', and, associated, clinical, features])]). relacion([sujeto(['We']), verbo([have]), complemento([developed, an, approach, for, directly, isolating, an, intact, 'multi-protein', chromatin, remodeling, complex, from, mammalian, cell, extracts, using, synthetic, peptide, affinity, reagent, 4])]). relacion([sujeto(['FOG1(1-15),', a, short, peptide, sequence, known, to]), verbo([target]), complemento([subunits, of, the, nucleosome, remodeling, and, deacetylase, '(', 'NuRD)', 'complex,', was, joined, via, a, 35, -, atom, hydrophilic, linker, to, the, 'StreptagII', peptide])]). relacion([sujeto(['Loading', this, peptide, onto, 'Streptactin', beads, enabled, capture, of, the, intact, 'NuRD', complex, from, 'MEL', cell]), verbo([nuclear]), complemento([extract])]). relacion([sujeto(['The', efficiency, of, 4, in, isolating, the, 'NuRD', complex, was, comparable, to, other]), verbo([reported]), complemento([methods, utilising, recombinantly, produced, 'GST-FOG1(1-45)'])]). relacion([sujeto(['We', previously]), verbo([reported]), complemento([that, 'TR2', and, 'TR4', orphan, nuclear, receptors, bind, to, direct, repeat, '(', 'DR)', elements, in, the, 'ε-', and, 'γ-globin', 'promoters,', and, act, as, molecular, anchors, for, the, recruitment, of, epigenetic, corepressors, of, the, multifaceted, 'DRED', 'complex,', thereby, leading, to, 'ε-', and, 'γ-globin', transcriptional, repression, during, definitive, erythropoiesis])]). relacion([sujeto(['Other', than, the, 'ε-', and, 'γ-globin', and, the, 'GATA1', 'genes,', 'TR4-regulated']), verbo([target]), complemento([genes, in, human, erythroid, cells, remain, unknown])]). relacion([sujeto(['Here,', we, identified, 'TR4']), verbo([binding]), complemento([sites, 'genome-wide', using, chromatin, immunoprecipitation, followed, by, massively, parallel, sequencing, '(', 'ChIP-seq)', as, human, primary, 'CD34(+)', hematopoietic, progenitors, differentiated, progressively, to, late, erythroid, precursors])]). relacion([sujeto(['We', also, performed, whole, transcriptome, analyses, by, 'RNA-seq', to, identify, 'TR4', downstream]), verbo([targets]), complemento([after, 'lentiviral-mediated', 'TR4', shRNA, knockdown, in, erythroid, cells])]). relacion([sujeto(['Analyses', from, combined, 'ChIP-seq', and, 'RNA-seq', datasets, indicate, that, 'DR1', motifs, are, more, prevalent, in, the, proximal, promoters, of, 'TR4', direct]), verbo([target]), complemento(['genes,', which, are, involved, in, basic, biological, functions, '(', e])]). relacion([sujeto(['In', 'contrast,', other, 'non-DR1', repeat, motifs, '(', 'DR4,', 'ER6', and, 'IR1)', are, more, prevalent, at, 'gene-distal', 'TR4']), verbo([binding]), complemento([sites])]). relacion([sujeto(['Of', 'these,', approximately, 50, '%', are, also, marked, with, epigenetic, chromatin, signatures, '(', such, as, 'P300,', 'H3K27ac,', 'H3K4me1', and, 'H3K27me3)']), verbo([associated]), complemento([with, enhancer, function])]). relacion([sujeto(['Thus,', we, hypothesize, that, 'TR4']), verbo([regulates]), complemento([gene, transcription, via, 'gene-proximal', 'DR1', sites, as, 'TR4/TR2', 'heterodimers,', while, it, can, associate, with, novel, nuclear, receptor, partners, '(', such, as, 'RXR)', to, bind, to, distant, 'non-DR1', consensus, sites])]). relacion([sujeto(['In', 'summary,', this, study]), verbo([reveals]), complemento([that, the, 'TR4', regulatory, network, is, far, more, complex, than, previously, appreciated, and, that, 'TR4', regulates, 'basic,', essential, biological, processes, during, the, terminal, differentiation, of, human, erythroid, cells])]). relacion([sujeto(['The', construction, of, network, models, of, 'cis-regulatory', 'elements,', 'therefore,']), verbo([has]), complemento([the, potential, to, generate, fundamental, insights, into, cellular, fate, and, differentiation])]). relacion([sujeto(['Haematopoiesis']), verbo([has]), complemento([long, served, as, a, model, system, to, study, mammalian, 'differentiation,', yet, modelling, based, on, experimentally, informed, 'cis-regulatory', interactions, has, so, far, been, restricted, to, pairs, of, interacting, factors])]). relacion([sujeto(['Here,', we]), verbo([have]), complemento([generated, a, 'Boolean', network, model, based, on, detailed, 'cis-regulatory', functional, data, connecting, 11, haematopoietic, 'stem/progenitor', cell, '(', 'HSPC)', regulator, genes])]). relacion([sujeto(['This', analysis, of, our, model, predicts, that, 'HSPCs', display, heterogeneous, expression, patterns, and, possess, many, intermediate, states, that, can]), verbo([act]), complemento([as, '\'', stepping, 'stones\'', for, the, 'HSPC', to, achieve, a, final, differentiated, state])]). relacion([sujeto(['Importantly,', an, external, perturbation, or, '\'', 'trigger\'', is]), verbo([required]), complemento([to, exit, the, stem, cell, 'state,', with, distinct, triggers, characterizing, maturation, into, the, various, different, lineages])]). relacion([sujeto(['In', 'conclusion,', we, demonstrate, that, an, advanced, mammalian, regulatory, network, model, based, on, experimentally, validated, 'cis-regulatory', interactions]), verbo([has]), complemento([allowed, us, to, make, 'novel,', experimentally, testable, hypotheses, about, transcriptional, mechanisms, that, control, differentiation, of, mammalian, stem, cells])]). relacion([sujeto(['Protein', arginine, methylation, is, emerging, as, a, pivotal, posttranslational, modification]), verbo([involved]), complemento([in, regulating, various, cellular, 'processes;', 'however,', its, role, in, erythropoiesis, is, still, elusive])]). relacion([sujeto(['Deficiency', in, erythroid, differentiation]), verbo([causes]), complemento([anemia, which, compromises, the, quality, of, life])]). relacion([sujeto(['Despite', extensive, 'studies,', the, molecular, events]), verbo([regulating]), complemento([erythropoiesis, are, not, fully, understood])]). relacion([sujeto(['This', study, showed, that, the]), verbo([increase]), complemento([in, protein, arginine, methyltransferase, 1, '(', 'PRMT1)', 'levels,', via, transfection, or, protein, 'transduction,', significantly, promoted, erythroid, differentiation, in, the, bipotent, human, 'K562', cell, line, as, well, as, in, human, primary, hematopoietic, progenitor, 'CD34(+)', cells])]). relacion([sujeto(['PRMT1', expression]), verbo([enhanced]), complemento([the, production, of, hemoglobin, and, the, erythroid, surface, marker, glycophorin, 'A,', and, also, 'up-regulated', several, key, transcription, 'factors,', 'GATA1,', 'NF-E2', and, 'EKLF,', which, are, critical, for, 'lineage-specific', differentiation])]). relacion([sujeto(['The', 'shRNA-mediated', knockdown, of, 'PRMT1']), verbo([suppressed]), complemento([erythroid, differentiation])]). relacion([sujeto(['The', methyltransferase, 'activity-deficient', 'PRMT1G80R', mutant, failed, to]), verbo([stimulate]), complemento(['differentiation,', indicating, the, requirement, of, arginine, methylation, of, target, proteins])]). relacion([sujeto(['Our', results, further, showed, that, a, specific, isoform, of, p38, 'MAPK,', 'p38α,']), verbo([promoted]), complemento([erythroid, 'differentiation,', whereas, p38β, did, not, play, a, role])]). relacion([sujeto(['PRMT1', appeared, to]), verbo([act]), complemento([upstream, of, 'p38α,', since, expression, of, p38α, still, promoted, erythroid, differentiation, in, 'PRMT1-knockdown', 'cells,', and, expression, of, 'PRMT1', enhanced, the, activation, of, p38, 'MAPK'])]). relacion([sujeto(['Importantly,', we, showed, for, the, first, time, that, 'PRMT1', was]), verbo([associated]), complemento([with, p38α, in, cells, by, 'co-immunoprecipitation', and, that, 'PRMT1', directly, methylated, p38α, in, in, vitro, methylation, assays])]). relacion([sujeto(['Taken', 'together,', our, findings, unveil, a, link, between, 'PRMT1', and, p38α, in]), verbo([regulating]), complemento([the, erythroid, differentiation, program, and, provide, evidence, suggesting, a, novel, regulatory, mechanism, for, p38α, through, arginine, methylation])]). relacion([sujeto(['We']), verbo([find]), complemento([that, erythroid, master, regulators, 'GATA1', and, 'TAL1', act, cooperatively, within, active, enhancers, but, confer, little, predictive, value, for, stage, specificity])]). relacion([sujeto(['HDAC1-containing', 'NuRD', complex, is]), verbo([required]), complemento([for, 'GATA-1-mediated', repression, and, activation])]). relacion([sujeto(['GATA-1']), verbo([associated]), complemento([with, acetylated, 'HDAC1-containing', 'NuRD', 'complex,', which, has, no, deacetylase, 'activity,', for, gene, activation])]). relacion([sujeto(['Histone', deacetylases, '(', 'HDACs)', play, important, roles, in]), verbo([regulating]), complemento([cell, proliferation, and, differentiation])]). relacion([sujeto(['The', 'HDAC1-containing', 'NuRD', complex, is, generally, considered, as, a, corepressor, complex, and, is]), verbo([required]), complemento([for, 'GATA-1-mediated', repression])]). relacion([sujeto(['However,', recent, studies, also, show, that, the, 'NuRD', complex, is]), verbo([involved]), complemento([in, 'GATA-1-mediated', gene, activation])]). relacion([sujeto(['We']), verbo([found]), complemento([that, 'GATA-1-associated', deacetylase, activity, gradually, decreased, upon, induction, of, erythroid, differentiation])]). relacion([sujeto(['It']), verbo([has]), complemento([been, demonstrated, earlier, that, acetylated, 'HDAC1', has, no, deacetylase, activity])]). relacion([sujeto(['Indeed,', overexpression, of, an, 'HDAC1', 'mutant,', which, mimics, acetylated, 'HDAC1,']), verbo([promotes]), complemento(['GATA-1-mediated', transcription, and, erythroid, differentiation])]). relacion([sujeto(['Furthermore,', during, erythroid, 'differentiation,', acetylated, 'HDAC1', recruitment, is]), verbo([increased]), complemento([at, 'GATA-1-activated', 'genes,', whereas, it, is, significantly, decreased, at, 'GATA-1-repressed', genes])]). relacion([sujeto(['Interestingly,', deacetylase, activity, is, not]), verbo([required]), complemento([for, 'Mi2', remodeling, 'activity,', suggesting, that, remodeling, activity, may, be, required, for, both, activation, and, repression])]). relacion([sujeto(['Thus,', our, data]), verbo([suggest]), complemento([that, 'NuRD', can, function, as, a, coactivator, or, repressor, and, that, acetylated, 'HDAC1', converts, the, 'NuRD', complex, from, a, repressor, to, an, activator, during, 'GATA-1-directed', erythroid, differentiation])]). relacion([sujeto(['Although', 'MLL-AF9']), verbo([caused]), complemento([by, the, chromosomal, translocation, 't(9;11)', has, a, critical, role, in, acute, myeloid, 'leukemia,', the, molecular, pathogenesis, is, poorly, understood])]). relacion([sujeto(['Recently', we, showed, that, the, forced, expression, of, 'DACH1', in, myeloid, cells]), verbo([induced]), complemento(['p27(Kip1)', and, repressed, 'p21(Cip1),', which, is, a, pivotal, characteristic, of, the, myeloid, progenitor])]). relacion([sujeto(['Moreover,', we, here, identified, an, endogenous, 'HOXA9-DACH1', complex]), verbo([mediated]), complemento([by, the, carboxyl, terminus, of, 'DACH1', in, 't(9;11)', leukemia, cells])]). relacion([sujeto(['qRT-PCR', revealed, that, 'DACH1']), verbo([has]), complemento([a, stronger, 'transcription-promoting', activity, with, 'HOXA9', than, does, 'PBX2', with, 'HOXA9'])]). relacion([sujeto(['Furthermore,', 'C/EBPα', and, 'GATA-1', can, directly]), verbo([bind]), complemento([to, the, promoter, of, 'DACH1', and, act, as, a, transcriptional, suppressor])]). relacion([sujeto(['However,', ectopic, expression, of, 'C/EBPα', 'and/or', 'GATA-1', could, not, abrogate, the, 'over-expression', of, 'DACH1']), verbo([induced]), complemento([by, 'MLL-AF9'])]). relacion([sujeto(['Therefore,', we, postulate, that, the, inability, of, 'C/EBPα', and, 'GATA-1', to, 'down-regulate', 'DACH1', expression]), verbo([induced]), complemento([by, 'MLL-AF9', during, myeloid, differentiation, may, contribute, to, 't(9;11)', leukemogenesis])]). relacion([sujeto(['Here', we, demonstrate, on, a, genome, wide, scale, that, the, hematopoietic, 'GATA', factors, 'GATA-1', and, 'GATA-2']), verbo([bind]), complemento([overlapping, sets, of, 'genes,', often, at, distinct, 'sites,', as, a, means, to, differentially, regulate, target, gene, expression, and, to, regulate, the, balance, between, proliferation, and, differentiation])]). relacion([sujeto(['We', also]), verbo([reveal]), complemento([that, the, 'GATA', 'switch,', which, entails, a, chromatin, occupancy, exchange, between, 'GATA2', and, 'GATA1', in, the, course, of, 'differentiation,', operates, on, more, than, 'one-third', of, 'GATA1', bound, genes])]). relacion([sujeto(['The', switch, is, equally, likely, to]), verbo([lead]), complemento([to, transcriptional, activation, or, 'repression;', and, in, 'general,', 'GATA1', and, 'GATA2', act, oppositely, on, switch, target, genes])]). relacion([sujeto(['Finally,', by, comparing, 'GATA1', occupancy, in, erythroid, cells, and, 'megakaryocytes,', we]), verbo([find]), complemento([that, the, presence, of, 'ETS', factor, motifs, is, a, major, discriminator, of, megakaryocyte, versus, red, cell, specification])]). relacion([sujeto(['Here', we]), verbo([report]), complemento([that, 'GATA-1,', 'SCL,', and, 'Klf1', form, an, erythroid, core, transcriptional, network, by, 'co-occupying', &, 'gt;300', genes])]). relacion([sujeto(['Importantly,', we]), verbo([find]), complemento([that, 'PU'])]). relacion([sujeto(['GATA-1,', 'SCL,', and, 'Klf1']), verbo([act]), complemento([to, 'promote,', whereas, 'PU'])]). relacion([sujeto([1, 'expression,', 'GATA-1', also]), verbo([binds]), complemento([to, and, represses, &, 'gt;100', 'PU'])]). relacion([sujeto([1, 'myelo-lymphoid', gene]), verbo([targets]), complemento([in, erythroid, progenitors])]). relacion([sujeto(['Mathematical', modeling, further, supports, that, this, dual, mechanism, of, repressing, both, the, opposing, upstream, activator, and, its, downstream]), verbo([targets]), complemento([provides, a, 'synergistic,', robust, mechanism, for, lineage, specification])]). relacion([sujeto(['Taken', 'together,', these, results, amalgamate, two, key, developmental, 'principles,', 'namely,', regulation, of, a, core, transcriptional, network, and, repression, of, an, alternative, transcriptional, 'program,', thereby]), verbo([enhancing]), complemento([our, understanding, of, the, mechanisms, that, establish, cellular, identity])]). relacion([sujeto(['The', transcription, factors, that, control, lineage, specification, of, haematopoietic, stem, cells, '(', 'HSCs)']), verbo([have]), complemento([been, well, described, for, the, myeloid, and, lymphoid, 'lineages,', whereas, transcriptional, control, of, erythroid, '(', 'E)', and, megakaryocytic, '(', 'Mk)', fate, is, less, understood])]). relacion([sujeto(['We', here, use, conditional, removal, of, the, 'GATA-1', and, 'FOG-1', transcription, factors, to, identify, 'FOG-1', as]), verbo([required]), complemento([for, the, formation, of, all, committed, 'Mk-', and, 'E-lineage', 'progenitors,', whereas, 'GATA-1', was, observed, to, be, specifically, required, for, 'E-lineage', commitment])]). relacion([sujeto(['These', results, identify, 'FOG-1', and, 'GATA-1', as]), verbo([required]), complemento([for, formation, of, bipotent, 'Mk/E', progenitors, and, their, 'E-lineage', 'commitment,', 'respectively,', and, show, that, 'FOG-1', mediates, transcriptional, 'Mk/E', programming, of, 'HSCs', as, well, as, their, subsequent, 'Mk/E-lineage', commitment])]). relacion([sujeto(['Mice']), verbo([expressing]), complemento([low, levels, of, 'c-Myb', '(', 'c-Myb(low))', have, an, increased, number, of, bone, marrow, megakaryocytes, '(', 'MKs)', and, corresponding, thrombocytosis])]). relacion([sujeto(['In', 'contrast,', mice, engineered, to]), verbo([express]), complemento([low, levels, of, 'GATA-1', '(', 'GATA-1(low))', in, the, megakaryocytic, lineage, exhibit, aberrant, megakaryocytopoiesis, with, hyperproliferation, of, progenitors, and, defective, terminal, differentiation, leading, to, thrombocytopenia])]). relacion([sujeto(['To', determine, how, these, two, transcription, factors]), verbo([act]), complemento([together, to, control, megakaryocytopoiesis, and, platelet, formation])]). relacion([sujeto(['We', used, a, combination, of, cellular, and, molecular, in, vitro, assays, to, examine, the, ability, of, bone, marrow, cells, from, mice]), verbo([expressing]), complemento([low, levels, of, both, 'c-Myb', and, 'GATA-1', '(', referred, to, as, 'double(low))', to, produce, 'MKs', and, platelets])]). relacion([sujeto(['c-Myb', and, 'GATA-1']), verbo([act]), complemento([in, concert, to, achieve, correct, megakaryocytic, differentiation])]). relacion([sujeto(['GATA-1']), verbo([regulates]), complemento([both, the, proliferation, of, megakaryocytic, progenitors, and, their, terminal, maturation])]). relacion([sujeto(['c-Myb', also]), verbo([acts]), complemento([at, the, level, of, the, progenitor, by, influencing, its, commitment, to, 'differentiation,', but, in, contrast, to, 'GATA-1', it, does, not, have, any, effect, on, the, process, of, terminal, differentiation])]). relacion([sujeto(['In', 'zebrafish,', homozygous, deletion, of, the, cdx4, gene, results, in, a, mutant, phenotype, known, as, 'kugelig,', with, aberrant, 'A-P', patterning, and, severe, anemia, characterized, by]), verbo([decreased]), complemento([gata1, expression, in, the, posterior, lateral, mesoderm])]). relacion([sujeto(['To', identify, pathways, that]), verbo([interact]), complemento([with, cdx4, during, primitive, 'hematopoiesis,', we, conducted, a, chemical, genetic, screen, in, the, cdx4, mutant, background, for, compounds, that, increase, gata1, expression, in, cdx4, mutants])]). relacion([sujeto(['The', strongest, rescue, was, observed, with, 'bergapten,', a, psoralen, compound]), verbo([found]), complemento([in, bergamont, oil])]). relacion([sujeto(['Another', member, of, the, psoralen, 'family,', 8, -, 'methoxypsoralen,', was, also]), verbo([found]), complemento([to, rescue, gata1, expression, in, 'cdx4-mutant', embryos])]). relacion([sujeto(['These', compounds, modify, the, 'cdx4-mutant', phenotype, and, will, help, elucidate, signaling, pathways, that]), verbo([act]), complemento([downstream, or, parallel, to, the, 'cdx4-hox', pathway])]). relacion([sujeto(['The', 'TALE-class', homeodomain, transcription, factors, 'Meis', and, 'Pbx', function, to]), verbo([regulate]), complemento([embryonic, 'hematopoiesis,', but, it, is, not, known, where, 'Meis', and, 'Pbx', proteins, participate, in, the, hematopoietic, transcription, factor, cascade])]). relacion([sujeto(['To', address, these, 'questions,', we]), verbo([have]), complemento([ablated, 'Meis1', and, 'Pbx', proteins, in, 'zebrafish,', and, characterized, their, molecular, effects, on, known, markers, of, primitive, hematopoiesis])]). relacion([sujeto(['Concomitant', with, a]), verbo([loss]), complemento([of, 'gata1,', 'Meis1-', and, 'Pbx-depleted', embryos, exhibit, downregulated, embryonic, hemoglobin, '(', 'hbae3)', 'expression,', and, possess, increased, numbers, of, pu])]). relacion([sujeto(['Our', study, conclusively, demonstrates, that, 'Meis1', and, 'Pbx']), verbo([act]), complemento([to, specify, the, erythropoietic, cell, lineage, and, inhibit, myelopoiesis])]). relacion([sujeto([1, /, 'Sfpi1', expression, is]), verbo([regulated]), complemento([by, 'GATA-1', and, 'GATA-2,', a, related, factor, that, is, normally, expressed, at, earlier, stages, of, hematopoiesis])]). relacion([sujeto(['Both', 'GATA', factors]), verbo([bind]), complemento([the, 'PU'])]). relacion([sujeto([1, /, 'Sfpi1', gene, at, 2, highly]), verbo([conserved]), complemento([regions])]). relacion([sujeto(['In', the, absence, of, 'GATA-1,', 'GATA-2']), verbo([binding]), complemento([is, associated, with, an, undifferentiated, 'state,', intermediate, level, 'PU'])]). relacion([sujeto([1, /, 'Sfpi1', 'expression,', and, 'low-level', expression, of, its, downstream, myeloid]), verbo([target]), complemento([genes])]). relacion([sujeto(['Restoration', of, 'GATA-1', function]), verbo([induces]), complemento([erythromegakaryocytic, differentiation])]). relacion([sujeto(['In', 'contrast,', when, 'GATA-1', is, not, 'present,', shRNA, knockdown, of, 'GATA-2']), verbo([increases]), complemento(['PU'])]). relacion([sujeto(['Our', findings, indicate, that, 'GATA', factors]), verbo([act]), complemento([sequentially, to, regulate, lineage, determination, during, 'hematopoiesis,', in, part, by, exerting, variable, repressive, effects, at, the, 'PU'])]). relacion([sujeto(['Although', leukemogenic, tyrosine, kinases, '(', 'LTKs)']), verbo([activate]), complemento([a, common, set, of, downstream, 'molecules,', the, phenotypes, of, leukemia, caused, by, 'LTKs', are, rather, distinct])]). relacion([sujeto(['Here', we]), verbo([report]), complemento([the, molecular, mechanism, underlying, the, development, of, hypereosinophilic, 'syndrome/chronic', eosinophilic, leukemia, by, 'FIP1L1-PDGFRalpha'])]). relacion([sujeto(['When', introduced, into, 'c-Kit(high)Sca-1(+)Lineage(-)', 'cells,', 'FIP1L1-PDGFRalpha']), verbo([conferred]), complemento(['cytokine-independent', growth, on, these, cells, and, enhanced, their, 'self-renewal,', whereas, it, did, not, immortalize, common, myeloid, progenitors, in, in, vitro, replating, assays, and, transplantation, assays])]). relacion([sujeto(['Importantly,', 'FIP1L1-PDGFRalpha', but, not, 'TEL-PDGFRbeta']), verbo([enhanced]), complemento([the, development, of, 'Gr-1(+)IL-5Ralpha(+)', eosinophil, progenitors, from, 'c-Kit(high)Sca-1(+)Lineage(-)', cells])]). relacion([sujeto(['FIP1L1-PDGFRalpha', also]), verbo([promoted]), complemento([eosinophil, development, from, common, myeloid, progenitors])]). relacion([sujeto(['Furthermore,', when]), verbo([expressed]), complemento([in, 'megakaryocyte/erythrocyte', progenitors, and, common, lymphoid, 'progenitors,', 'FIP1L1-PDGFRalpha', not, only, inhibited, differentiation, toward, erythroid, 'cells,', 'megakaryocytes,', and, 'B-lymphocytes', but, aberrantly, developed, eosinophil, progenitors, from, 'megakaryocyte/erythrocyte', progenitors, and, common, lymphoid, progenitors])]). relacion([sujeto(['As', for, the, mechanism, of, 'FIP1L1-PDGFRalpha-induced', eosinophil, 'development,', 'FIP1L1-PDGFRalpha', was]), verbo([found]), complemento([to, more, intensely, activate, 'MEK1/2', and, 'p38(MAPK)', than, 'TEL-PDGFRbeta'])]). relacion([sujeto(['In', 'addition,', a, 'MEK1/2', inhibitor, and, a, 'p38(MAPK)', inhibitor]), verbo([suppressed]), complemento(['FIP1L1-PDGFRalpha-promoted', eosinophil, development])]). relacion([sujeto(['In', 'addition,', short, hairpin, 'RNAs', against, 'C/EBPalpha', and, 'GATA-2', and, 'GATA-3KRR,', which, can]), verbo([act]), complemento([as, a, 'dominant-negative', form, over, all, 'GATA', 'members,', inhibited, 'FIP1L1-PDGFRalpha-induced', eosinophil, development])]). relacion([sujeto(['Furthermore,', 'FIP1L1-PDGFRalpha', and, its, downstream, 'Ras']), verbo([inhibited]), complemento(['PU'])]). relacion([sujeto(['Together,', these, results, indicate, that, 'FIP1L1-PDGFRalpha']), verbo([enhances]), complemento([eosinophil, development, by, modifying, the, expression, and, activity, of, 'lineage-specific', transcription, factors, through, 'Ras/MEK', and, 'p38(MAPK)', cascades])]). relacion([sujeto(['While', some, studies, show, that, highly, constrained, noncoding, regions]), verbo([act]), complemento([to, enhance, 'transcription,', other, studies, show, that, 'DNA', segments, with, biochemical, signatures, of, regulatory, 'regions,', such, as, occupancy, by, a, transcription, 'factor,', are, seemingly, unconstrained, across, mammalian, evolution])]). relacion([sujeto(['DNA', segments]), verbo([bound]), complemento([by, 'GATA1', were, identified, by, hybridization, to, 'high-density', tiling, 'arrays,', validated, by, quantitative, 'PCR,', and, tested, for, gene, regulatory, activity, in, erythroid, cells])]). relacion([sujeto(['Whereas', almost, all, of, the, occupied, segments, contain, canonical, 'WGATAR']), verbo([binding]), complemento([site, motifs, for, 'GATA1,', in, only, 45, '%', of, the, cases, is, the, motif, deeply, preserved, '(', found, at, the, orthologous, position, in, placental, mammals, or, more, distant, 'species)'])]). relacion([sujeto(['Thus,', 'GATA1']), verbo([binding]), complemento([sites, that, regulate, gene, expression, during, erythroid, maturation, are, under, strong, selective, 'constraint,', while, nonconstrained, binding, may, have, only, a, limited, or, indirect, role, in, regulation])]). relacion([sujeto(['The', alpha, and, beta, isoforms, of, the, human, thromboxane, 'A(2)', '(', 'TXA(2))', receptor, '(', 'TP)', are, encoded, by, a, single, gene, but, are, transcriptionally]), verbo([regulated]), complemento([by, distinct, 'promoters,', termed, promoter, 1, '(', 'Prm1)', and, 'Prm3,', respectively])]). relacion([sujeto(['Herein,', it, was, sought, to, identify, factors]), verbo([regulating]), complemento(['Prm1', within, the, megakaryocytic, human, erythroleukemia, 92.1])]). relacion([sujeto(['Electrophoretic', mobility, shift, assays, and, chromatin, immunoprecipitations, confirmed, that, 'Sp1,', 'Egr1,', and, 'NF-E2']), verbo([bind]), complemento([to, elements, within, the, core, 'promoter,', whereas, 'GATA-1', and, 'Ets-1', factors, bind, to, the, upstream, activator, sequence, '(', between, -, 7, ',', 962, and, -, 7, ',', 717, ')'])]). relacion([sujeto(['Collectively,', these, data, establish, that, 'Sp1,', 'Egr1,', and, 'NF-E2']), verbo([regulate]), complemento([core, 'Prm1', activity, in, the, 'megakaryocytic-platelet', progenitor, 'cells,', whereas, 'GATA-1', and, 'Ets-1', act, as, critical, upstream, 'activators,', hence, providing, the, first, genetic, basis, for, the, expression, of, the, human, 'TXA(2)', receptor, '(', 'TP)', within, the, vasculature])]). relacion([sujeto(['The', 'WGATAR', motif, is, a, common, nucleotide, sequence]), verbo([found]), complemento([in, the, transcriptional, regulatory, regions, of, numerous, genes])]). relacion([sujeto(['In', 'vertebrates,', these, motifs, are]), verbo([bound]), complemento([by, one, of, six, factors, '(', 'GATA1', to, 'GATA6)', that, constitute, the, 'GATA', family, of, transcriptional, regulatory, proteins])]). relacion([sujeto(['Although', originally, considered, for, their, roles, in, hematopoietic, cells, and, the, 'heart,', 'GATA', factors, are, now, known, to, be]), verbo([expressed]), complemento([in, a, wide, variety, of, tissues, where, they, act, as, critical, regulators, of, 'cell-specific', gene, expression])]). relacion([sujeto(['Insights', into, the, functional, roles, played, by, 'GATA', factors, in, adult, organ, systems]), verbo([have]), complemento([been, hampered, by, the, early, embryonic, lethality, associated, with, the, different, 'Gata-null', mice])]). relacion([sujeto(['These', 'approaches,', together, with, the]), verbo([increasing]), complemento([number, of, human, 'GATA-related', pathologies, have, greatly, broadened, the, scope, of, 'GATA-dependent', genes, 'and,', 'importantly,', have, shown, that, 'GATA', action, is, not, necessarily, limited, to, early, development])]). relacion([sujeto(['This']), verbo([has]), complemento([been, particularly, evident, in, endocrine, organs, where, 'GATA', factors, appear, to, contribute, to, the, transcription, of, multiple, 'hormone-encoding', genes])]). relacion([sujeto(['This', review]), verbo([provides]), complemento([an, overview, of, the, 'GATA', family, of, transcription, factors, as, they, relate, to, endocrine, function, and, disease])]). relacion([sujeto(['We']), verbo([have]), complemento([shown, previously, that, 'Hls7/Mlf1', imposes, a, monoblastoid, phenotype, on, erythroleukemic, cells])]). relacion([sujeto(['Here', we, show, that, 'Hls5', impedes, erythroid, maturation, by, restricting, proliferation, and]), verbo([inhibiting]), complemento([hemoglobin, 'synthesis;', 'however,', 'Hls5', does, not, influence, the, morphology, of, erythroid, cells])]). relacion([sujeto(['Under', the, influence, of, 'GATA-1,', 'Hls5', relocates, from, cytoplasmic, granules, to, the, nucleus, where, it]), verbo([associates]), complemento([with, both, 'FOG-1', and, 'GATA-1'])]). relacion([sujeto(['In', the, 'nucleus,', 'Hls5', is, able, to]), verbo([suppress]), complemento(['GATA-1-mediated', transactivation, and, reduce, 'GATA-1', binding, to, 'DNA'])]). relacion([sujeto(['We', conclude, that, 'Hls5', and, 'Hls7/Mlf1']), verbo([act]), complemento([cooperatively, to, induce, biochemical, and, phenotypic, changes, associated, with, 'erythroid/myeloid', lineage, switching])]). relacion([sujeto(['Development', in, higher, eukaryotes]), verbo([involves]), complemento([programmed, gene, expression])]). relacion([sujeto(['Higher', eukaryotes]), verbo([have]), complemento([evolved, elegant, mechanisms, by, which, committed, 'gene-expression', states, are, transmitted, through, numerous, cell, divisions])]). relacion([sujeto(['Previous', studies]), verbo([have]), complemento([shown, that, both, 'DNase', 'I-sensitive', sites, and, the, basal, transcription, factor, 'TFIID', remain, on, silenced, mitotic, 'chromosomes,', suggesting, that, certain, 'trans-factors', might, act, as, 'bookmarks,', maintaining, the, information, and, transmitting, it, to, the, next, generation])]). relacion([sujeto(['In', cells]), verbo([arrested]), complemento([in, 'mitosis,', the, 'erythroid-specific', activator, 'NF-E2p45', remained, associated, with, its, binding, sites, on, the, globin, gene, 'loci,', while, the, other, major, erythroid, 'factor,', 'GATA-1,', was, removed, from, chromosome])]). relacion([sujeto(['Our', results, imply, that, certain, kinds, of, specific, protein, factors, and, active, histone, modifications, function, as, cellular, memory, markers, for, both, competent, and, active, genes, during, 'mitosis,', and, serve, as, a]), verbo([reactivated]), complemento([core, for, the, resumption, of, transcription, when, the, cells, exit, mitosis])]). relacion([sujeto(['Mutations', of, the, 'GATA1', gene, on, chromosome, 'X']), verbo([have]), complemento([been, found, in, almost, all, cases, of, transient, myeloproliferative, disorder, and, acute, megakaryoblastic, leukemia, '(', 'AMKL)', accompanying, 'Down', syndrome, '(', 'DS)'])]). relacion([sujeto(['Although', most, 'GATA1', mutations]), verbo([lead]), complemento([to, the, expression, of, 'GATA1s', lacking, the, 'N-terminal', activation, 'domain,', we, recently, found, two, novel, 'GATA1', proteins, with, defects, in, another, 'N-terminal', region])]). relacion([sujeto(['It']), verbo([has]), complemento([been, suggested, that, loss, of, the, 'N-terminal', portion, of, 'GATA1', might, interfere, with, physiological, interactions, with, the, critical, megakaryocytic, transcription, factor, 'RUNX1,', and, this, would, imply, that, 'GATA1s', is, not, able, to, interact, properly, with, 'RUNX1'])]). relacion([sujeto(['In', this, 'study,', we, show, that, 'GATA1']), verbo([binds]), complemento([to, 'RUNX1', through, its, 'zinc-finger', 'domains,', and, that, the, 'C-finger', is, indispensable, for, synergy, with, 'RUNX1'])]). relacion([sujeto(['All', of, the, 'patient-specific', 'GATA1', mutants]), verbo([interacted]), complemento([efficiently, with, 'RUNX1', and, retained, their, ability, to, act, synergistically, with, 'RUNX1', on, the, megakaryocytic, 'GP1balpha', 'promoter,', whereas, the, levels, of, transcriptional, activities, were, diverse, among, the, mutants])]). relacion([sujeto(['Thus,', our, data, indicate, that, physical, interaction, and, synergy, between, 'GATA1', and, 'RUNX1', are]), verbo([retained]), complemento([in, 'DS-AMKL,', although, it, is, still, possible, that, increased, 'RUNX1', activity, plays, a, role, in, the, development, of, leukemia, in, 'DS'])]). relacion([sujeto(['It']), verbo([requires]), complemento([a, potentially, 'multi-step', decision, sequence, which, determines, the, fate, of, the, cells, and, their, successors])]). relacion([sujeto(['It', is, generally, accepted, that, lineage, specification, is]), verbo([regulated]), complemento([by, a, complex, system, of, interacting, transcription, factors])]). relacion([sujeto([1, ',', both, known, to]), verbo([act]), complemento([as, key, regulators, and, potential, antagonists, in, the, erythroid, vs])]). relacion([sujeto(['Whereas']), verbo([increasing]), complemento([transcription, rates, are, sufficient, to, induce, differentiation, in, one, 'scenario,', an, additional, system, perturbation, '(', by, stochastic, fluctuations, or, directed, 'impulses)', of, transcription, factor, levels, is, required, in, the, other, case])]). relacion([sujeto(['Here', we, showed, that, in, erythroid, 'K562', cells, these, 'DNA', motifs]), verbo([bound]), complemento([the, following, three, transcription, 'factors:', ubiquitous, 'NF-Y', and, hematopoietic, 'MZF1', and, 'GATA-2'])]). relacion([sujeto(['These', factors, and, their]), verbo([target]), complemento(['DNA', motifs, exhibited, a, hierarchy, of, 'DNA/protein', and, 'protein/protein', binding, 'affinities:', 'NF-Y/CCAAT', &, 'gt;', 'NF-Y/GATA-2', &, 'gt;', 'NF-Y/MZF1', &, 'gt;', 'MZF1/GTGGGGA;', 'GATA-2/GATA'])]). relacion([sujeto(['Through', 'protein/protein', 'interactions,', 'NF-Y']), verbo([bound]), complemento([at, the, 'CCAAT', motif, recruited, 'MZF1', and, 'GATA-2,', but, not, 'Sp1', and, 'GATA-1,', and, stabilized, their, binding, to, the, neighboring, 'GTGGGGA', and, 'GATA', sites, to, assemble, a, novel, 'LTR', enhancer, 'complex,', 'NF-Y/MZF1/GATA-2'])]). relacion([sujeto(['In', the, 'LTR-HS5-epsilonp-GFP', plasmid, integrated, into, 'K562', 'cells,', mutation, of, the, 'CCAAT', motif, in, the, 'LTR', enhancer, to, abolish, 'NF-Y']), verbo([binding]), complemento([inactivated, the, 'enhancer,', closed, down, the, chromatin, structure, of, the, 'epsilon-globin', 'promoter,', and, silenced, transcription, of, the, green, fluorescent, protein, gene])]). relacion([sujeto(['The', results, indicated, that, 'NF-Y']), verbo([bound]), complemento([at, the, 'CCAAT', motifs, assembled, a, robust, 'LTR', enhancer, 'complex,', which, could, act, over, the, intervening, 'DNA', to, remodel, the, chromatin, structure, and, to, stimulate, the, transcription, of, the, downstream, gene, locus])]). relacion([sujeto(['GATA-1', and, friend, of, 'GATA', '(', 'FOG)', are, 'zinc-finger', transcription, factors, that, physically]), verbo([interact]), complemento([to, play, essential, roles, in, erythroid, and, megakaryocytic, development])]). relacion([sujeto(['Several', naturally, occurring, mutations, in, the, 'GATA-1', gene, that, alter, the, 'FOG-binding', domain]), verbo([have]), complemento([been, reported])]). relacion([sujeto(['The', mutations, are]), verbo([associated]), complemento([with, familial, anemias, and, thrombocytopenias, of, differing, severity])]). relacion([sujeto(['To', elucidate, the, molecular, basis, for, the, 'GATA-1/FOG', 'interaction,', we]), verbo([have]), complemento([determined, the, 'three-dimensional', structure, of, a, complex, comprising, the, interaction, domains, of, these, proteins])]). relacion([sujeto(['The', structure]), verbo([reveals]), complemento([how, zinc, fingers, can, act, as, protein, recognition, motifs])]). relacion([sujeto(['Details', of, the, architecture, of, the, contact, domains, and, their, physical, properties]), verbo([provide]), complemento([a, molecular, explanation, for, how, the, 'GATA-1', mutations, contribute, to, distinct, but, related, genetic, diseases])]). relacion([sujeto(['Both']), verbo([nuclear]), complemento([factor, erythroid, 2, 45, kDa, subunit, '(', 'p45)', and, 'BTB', and, 'CNC', homolog, 1, '(', 'Bach)', transcription, factors, can, form, dimers, with, one, of, the, small, 'Maf', 'proteins,', and, these, heterodimers, bind, to, the, musculoaponeurotic, fibrosarcoma, oncogene, '(', 'Maf)', recognition, element, '(', 'MARE)'])]). relacion([sujeto(['MARE', is, known, to]), verbo([act]), complemento([as, a, critical, 'cis-regulatory', element, of, erythroid, and, megakaryocytic, genes])]). relacion([sujeto(['The', transgenic, mouse, lines, showed, significant, thrombocytopenia]), verbo([associated]), complemento([with, impaired, maturation, of, the, 'megakaryocytes,', and, they, developed, myelofibrosis])]). relacion([sujeto(['Transcription', of, the, p45]), verbo([target]), complemento([genes, was, 'down-regulated', and, we, indeed, found, that, 'BACH1', binds, to, the, thromboxane, synthase, 'gene,', one, of, the, target, genes, for, p45, in, megakaryocytes])]). relacion([sujeto(['These', findings, thus]), verbo([provide]), complemento([evidence, that, 'BACH1', acts, as, a, transcriptional, repressor, in, the, regulation, of, 'MARE-dependent', genes, in, megakaryocytes])]). relacion([sujeto(['Recently,', 'Ski', was, shown, to]), verbo([act]), complemento([in, distinct, signaling, pathways, including, those, involving, nuclear, 'receptors,', transforming, growth, factor, 'beta,', and, tumor, suppressors])]). relacion([sujeto(['These', divergent, roles, of, 'Ski', are, probably, dependent, on, 'Ski\'s', capacity, to]), verbo([bind]), complemento([multiple, partners, with, disparate, functions])]). relacion([sujeto(['In', 'particular,', 'Ski', alters, the, growth, and, differentiation, program, of, erythroid, progenitor, 'cells,']), verbo([leading]), complemento([to, malignant, leukemia])]). relacion([sujeto(['However,', the, mechanism, underlying, this, important, effect]), verbo([has]), complemento([remained, elusive])]). relacion([sujeto(['Here', we, show, that, 'Ski']), verbo([interacts]), complemento([with, 'GATA1,', a, transcription, factor, essential, in, erythropoiesis])]). relacion([sujeto(['Furthermore,', the, repression, of, 'GATA1-mediated', transcription]), verbo([involves]), complemento(['Ski\'s', ability, to, block, 'DNA', binding, of, 'GATA1'])]). relacion([sujeto(['This']), verbo([finding]), complemento([is, in, marked, contrast, to, those, in, previous, reports, on, the, mechanism, of, repression, by, 'Ski,', which, have, described, a, model, involving, the, recruitment, of, corepressors, into, 'DNA-bound', transcription, complexes])]). relacion([sujeto(['Vertebrate', 'GATA', proteins]), verbo([regulate]), complemento([processes, that, are, vital, to, 'development,', and, each, possesses, two, tandem, 'GATA', finger, 'domains:', an, 'N-terminal', 'GATA', finger, and, a, 'C-terminal', 'GATA', finger])]). relacion([sujeto(['These', 'GATA', fingers]), verbo([require]), complemento(['Zn(2+)', to, 'fold,', to, bind, 'DNA', recognition, 'elements,', and, to, regulate, transcription])]). relacion([sujeto(['While', the, 'GATA-1', 'C-terminal', finger, is, necessary, and, sufficient, to]), verbo([bind]), complemento([to, single, 'GATA', 'DNA', 'sites,', the, 'N-terminal', finger, interacts, with, 'DNA', such, that, the, double, finger, unit, '(', 'DF', 'domain)', has, a, binding, and, transactivation, profile, that, is, tuned, by, the, 'DNA-binding', site])]). relacion([sujeto(['Co(2+)', was, used, as, a, spectroscopic, probe, in, a, series, of, competition, titrations, to, determine, the, affinity, of, 'Co(2+)', and, 'Zn(2+)', for, the, 'C-terminal', finger, from, chicken, 'GATA-1', and, the, double, finger, from, human, 'GATA-1', '(', referred, to, in, this]), verbo([report]), complemento([as, 'CF', and, 'DF)'])]). relacion([sujeto(['For', 'DF,', these, experiments, yielded, equilibrium, constants, for, the, process, of, two, 'M(2+)']), verbo([binding]), complemento([to, form, 'M(2+)(2)-DF', of, 'beta(2)(Co)', =, 2.5, '(', +, /, -, 1.6, ')', x, 10, '(', 14, ')', 'M(-2)', and, 'beta(2)(Zn)', =, 6.3, '(', +, /, -, 2.5, ')', x, 10, '(', 20, ')', 'M(-2)'])]). relacion([sujeto(['A', detailed, analysis, of, these, data]), verbo([suggests]), complemento([that, the, 'N-terminal', and, 'C-terminal', fingers, of, 'DF', act, as, independent, and, identical, 'Zn(2+)-binding', sites, and, each, finger, binds, 'Zn(2+)', with, an, affinity, equivalent, to, that, of, 'CF'])]). relacion([sujeto(['The', locus, control, region, of, the, 'beta-globin', gene, cluster]), verbo([has]), complemento([been, used, previously, to, direct, erythroid, expression, of, globin, genes, from, retroviral, vectors, for, the, purpose, of, gene, therapy])]). relacion([sujeto(['In', this, 'work,', we]), verbo([have]), complemento([functionally, studied, an, additional, 'GATA-1', 'enhancer,', 'HS1'])]). relacion([sujeto(['HS1']), verbo([participates]), complemento([in, the, transcriptional, autoregulation, of, 'GATA-1', through, an, essential, 'GATA-binding', site, that, is, footprinted, in, vivo])]). relacion([sujeto(['In', this, work, we, identified, within, 'HS1', a, new, in, vivo, footprinted, 'region,', and, we, showed, that, this, sequence, indeed]), verbo([binds]), complemento([a, nuclear, protein, in, vitro])]). relacion([sujeto(['The', deletion, of, the, newly, identified, footprinted, sequence, in, the, retroviral, construct, further]), verbo([increases]), complemento([expression, up, to, a, level, almost, equal, to, that, of, the, wild, type, retroviral, 'LTR,', without, loss, of, erythroid, 'specificity,', suggesting, that, this, sequence, may, act, as, a, negative, regulatory, element])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, substantial, improvement, of, overall, expression, can, be, achieved, by, the, combination, of, multiple, changes, in, both, regulatory, elements, and, vectors])]). relacion([sujeto(['The', two, proteins]), verbo([bind]), complemento([to, one, another, and, inhibit, each, 'other\'s', function, in, transcriptional, activation, and, promotion, of, their, respective, differentiation, programs])]). relacion([sujeto([1, can, also]), verbo([act]), complemento([as, an, oncoprotein, since, deregulated, expression, of, 'PU'])]). relacion([sujeto([1, in, erythroid, precursors]), verbo([causes]), complemento([erythroleukemias, in, mice])]). relacion([sujeto(['We']), verbo([have]), complemento([investigated, the, mechanism, of, 'PU'])]). relacion([sujeto([1, -]), verbo([mediated]), complemento([repression, of, 'GATA-1'])]). relacion([sujeto(['We']), verbo([report]), complemento([here, that, 'PU'])]). relacion([sujeto([1]), verbo([binds]), complemento([to, 'GATA-1', on, 'DNA'])]). relacion([sujeto([1, to, a, small, acidic, 'N-terminal', domain, that]), verbo([interacts]), complemento([with, the, 'C', pocket, of, 'pRB,', a, 'well-known', transcriptional, corepressor])]). relacion([sujeto([1]), verbo([requires]), complemento(['pRB,', and, pRB, colocalizes, with, 'PU'])]). relacion([sujeto([1, and, 'GATA-1', at, repressed, 'GATA-1']), verbo([target]), complemento([genes])]). relacion([sujeto(['Our', results]), verbo([suggest]), complemento([that, one, of, the, mechanisms, by, which, 'PU'])]). relacion([sujeto([1, antagonizes, 'GATA-1', is, by]), verbo([binding]), complemento([to, it, at, 'GATA-1', target, genes, and, tethering, to, these, sites, a, corepressor, that, blocks, transcriptional, activity, and, thereby, erythroid, differentiation])]). relacion([sujeto(['To', investigate, the, effect, of, the, human, 'A', 'gamma-globin', 'gene-173', 'T-->C', mutation, on, the]), verbo([binding]), complemento([of, transacting, factors, to, the, promoter, and, the, activity, of, the, promoter])]). relacion([sujeto(['The', 'A', 'gamma-globin', 'gene-173', 'T-->C', mutation]), verbo([decreased]), complemento([the, affinity, of, 'GATA-1', to, the, mutant, promoter, fragment, '(', -, 201, '(', -, ')', -, 158, ')', 96, '%', '(', 'P', &, 'lt;', 0.01, ')', and, the, binding, of, 'Oct-1', to, the, same, 'DNA', fragment, 55, '%', '(', 'P', &, 'lt;', 0.05, ')'])]). relacion([sujeto(['The', -, 173, 'T-->C', mutation]), verbo([decreased]), complemento([dramatically, the, binding, of, 'GATA-1,', implicating, that, 'GA-TA-1', may, act, as, a, negative, regulator, of, 'A', 'gamma-globin', gene, in, adults])]). relacion([sujeto(['The', -, 173, 'T-->C', mutation, may]), verbo([enhance]), complemento([the, activity, of, 'A', 'gamma-globin', gene, promoter, in, the, adult, erythroid, cell, environment])]). relacion([sujeto(['Megakaryocytopoiesis']), verbo([involves]), complemento([the, proliferation, and, differentiation, of, megakaryocytic, pro, genitor, cells, into, immature, 'megakaryocytes,', and, the, differentiation, of, immature, megakaryocytes, to, mature, megakaryocytes, which, produce, platelets])]). relacion([sujeto(['The', former, is]), verbo([regulated]), complemento([mainly, by, thrombopoietin, '(', 'TPO)', and, to, a, lesser, degree, by, other, cytokines, such, as, 'interleukin-1', '(', 'IL-1),', 'IL-3', and, 'platelet-derived', growth, factor, '(', 'PDGF),', the, later, by, 'TPO', and, probably, 'IL-6', and, 'IL-11'])]). relacion([sujeto(['A', number, of, transcription, factors]), verbo([have]), complemento([been, implicated, in, the, control, of, megakaryocyte, differentiation])]). relacion([sujeto(['NF-E2']), verbo([regulates]), complemento(['late-stage', of, megakaryocytopoiesis, and, platelet, production])]). relacion([sujeto(['However,', the, platelet]), verbo([release]), complemento([mechanism, is, poorly, understood])]). relacion([sujeto(['Nitric', oxide, '(', 'NO)', may]), verbo([act]), complemento([in, the, stage, of, platelet, release, through, induction, of, apoptosis, in, megakaryocytes])]). relacion([sujeto(['However,', previous, studies, indicate, that, 'FOG-1', may, play, a, 'GATA-1-independent', role, in, early, 'megakaryopoiesis,']), verbo([suggesting]), complemento([that, 'FOG', proteins, might, act, in, a, 'GATA', 'factor-independent', manner])]). relacion([sujeto(['Here,', we]), verbo([have]), complemento([generated, mouse, 'knock-in', '(', 'KI)', mutants, harboring, a, critical, 'valine-to-glycine', substitution, in, the, 'amino-terminal', zinc, fingers, of, 'GATA-1', and, 'GATA-2', to, ablate, 'FOG', interaction])]). relacion([sujeto(['We', conclude, that, 'FOG-1']), verbo([requires]), complemento([an, interaction, with, either, 'GATA-1', or, -, 2, as, part, of, its, essential, role, in, early, megakaryopoiesis])]). relacion([sujeto(['Gene']), verbo([targeting]), complemento([experiments, in, the, mouse, have, demonstrated, key, roles, for, the, basic, 'helix-loop-helix', transcription, factor, 'SCL', and, the, 'GATA-binding', protein, 'GATA-1', in, hematopoiesis])]). relacion([sujeto(['Forced', expression, of, either, factor, in, whole, 'embryos,', 'however,', does, not]), verbo([lead]), complemento([to, ectopic, blood, formation])]). relacion([sujeto(['This', apparent, paradox, between, animal, cap, assays, and, whole, embryo, phenotype]), verbo([has]), complemento([led, to, the, hypothesis, that, additional, factors, are, involved, in, specifying, hematopoietic, mesoderm])]). relacion([sujeto(['SCL', and, 'GATA-1']), verbo([interact]), complemento([in, a, transcriptional, complex, with, the, 'LIM', domain, protein, 'LMO-2'])]). relacion([sujeto(['We']), verbo([have]), complemento([cloned, the, 'Xenopus', homolog, of, 'LMO-2', and, show, that, it, is, expressed, in, a, similar, pattern, to, 'SCL', during, development])]). relacion([sujeto(['SCL', and, 'LMO-2']), verbo([act]), complemento([synergistically, to, expand, the, blood, island, when, overexpressed, in, whole, embryos])]). relacion([sujeto(['Furthermore,', 'co-expression', of, 'GATA-1', with, 'SCL', and, 'LMO-2']), verbo([leads]), complemento([to, embryos, that, are, ventralized, and, have, blood, throughout, the, 'dorsal-ventral', axis])]). relacion([sujeto(['The', synergistic, effect, of, 'SCL,', 'LMO-2', and, 'GATA-1,', taken, together, with, the, findings, that, these, factors, can, form, a, complex, in, 'vitro,']), verbo([suggests]), complemento([that, this, complex, specifies, mesoderm, to, become, blood, during, embryogenesis])]). relacion([sujeto(['We']), verbo([have]), complemento([recently, demonstrated, that, a, testicular, 'GATA-binding', 'protein,', 'GATA-1,', 'up-regulates', the, transcription, of, inhibin, 'alpha-subunit', gene, through, interaction, with, 'GATA', motifs, in, the, promoter, region, in, 'MA-10,', a, mouse, 'Leydig', tumor, cell, line])]). relacion([sujeto(['The', abilities, of, 'GATA-1', and, 'GATA-4']), verbo([interacting]), complemento([with, 'GATA', 'and/or', 'GATA-like', sequences, to, transactivate, the, 'beta-B(4'])]). relacion([sujeto(['Mutations', of, 'GATA', or, 'GATA-like', sequences]), verbo([caused]), complemento([no, apparent, effect, or, only, a, small, decrease, in, the, basal, transcriptional, activity, of, this, promoter])]). relacion([sujeto(['However,', mutation, of, the, 'GATA', motif, at, -, 65, markedly]), verbo([decreased]), complemento([60, -, 70, '%', of, the, effect, of, 'GATA-1', on, the, transactivation, of, 'beta-B(4'])]). relacion([sujeto(['Interestingly,', mutation, of, 'GATT', at, -, 42]), verbo([caused]), complemento([a, 70, -, 90, '%', increase, in, the, transactivation, of, 'beta-B(4'])]). relacion([sujeto(['Electrophoretic', mobility, shift, assay, confirmed, the, above, observations, that, these, 'GATA-binding', proteins]), verbo([interacted]), complemento([with, the, 'GATA', motif, at, -, 65, and, 'GATT', at, -, 42, ',', but, not, with, 'GATC', at, -, 201, or, 'GATT', at, -, 177])]). relacion([sujeto(['Serial', deletion, from, the, 5, '\'', -, end, of, the, basal, 'promoter,', from, -, 226, to, -, 90, ',', markedly]), verbo([decreased]), complemento([the, basal, 'transcription,', but, increased, the, effect, of, 'GATA-1', on, transactivation, of, the, 'beta-B(4'])]). relacion([sujeto(['In', 'summary,', our, observations]), verbo([suggest]), complemento([that, the, two, 'GATA-binding', proteins, transactivate, the, 'beta-B(4'])]). relacion([sujeto(['Both', 'GATA-1', and, 'GATA-4', factors]), verbo([act]), complemento([through, the, 'GATA', motif, at, -, 65, and, 'GATT', at, -, 42, to, positively, and, negatively, regulate, the, transcription, from, this, 'promoter,', respectively])]). relacion([sujeto(['Furthermore,', 'GATA-1', may, also]), verbo([interact]), complemento([directly, or, indirectly, with, 'DNA', sequences, at, -, 180, to, -, 90, to, regulate, the, 'beta-B(4'])]). relacion([sujeto(['We', examined, the, potential, of, mutant, embryonic, stem, cell, lines, harboring]), verbo([targeted]), complemento([deletions, of, the, 'GATA-1,', 'FOG,', 'SCL/tal-1,', or, 'GATA-2', genes, to, differentiate, into, osteoclasts, and, determined, when, these, molecules, function, in, osteoclast, development])]). relacion([sujeto(['In', the, case, of, the]), verbo([loss]), complemento([of, 'GATA-2,', a, small, number, of, osteoclasts, were, generated])]). relacion([sujeto(['Experiments', using, specific, inhibitors, that, block, the, signaling, through, macrophage, 'colony-stimulating', factor, and, osteoclast, differentiation, 'factor/osteoprotegerin', ligand]), verbo([suggested]), complemento([that, 'GATA-2', seems, to, act, earlier, in, osteoclastogenesis, than, these, cytokines])]). relacion([sujeto(['Interestingly,', macrophage, 'colony-forming', units, were, not, severely, reduced, by, the]), verbo([loss]), complemento([of, 'GATA-2', compared, to, osteoclast, progenitors])]). relacion([sujeto(['These', results, indicate, that, osteocalsts, need, 'SCL/tal-1', at, an, early, point, in, 'development,', and, that, 'GATA-2', is]), verbo([required]), complemento([for, generation, of, osteoclast, progenitors, but, not, for, the, later, stages, when, macrophage, 'colony-stimulating', factor, and, osteoclast, differentiation, 'factor/', osteoprotegerin, ligand, are, needed])]). relacion([sujeto(['Members', of, the, 'GATA', family, of, 'zinc-finger', transcription, factors]), verbo([have]), complemento([critical, roles, in, a, variety, of, cell, types])]). relacion([sujeto(['GATA-1,', 'GATA-2', and, 'GATA-3', are]), verbo([required]), complemento([for, proliferation, and, differentiation, of, several, hematopoietic, 'lineages,', whereas, 'GATA-4,', 'GATA-5', and, 'GATA-6', activate, cardiac, and, endoderm, gene, expression, programs])]). relacion([sujeto(['Two', 'GATA', cofactors]), verbo([have]), complemento([recently, been, identified])]). relacion([sujeto(['Friend', of, 'GATA-1', '(', 'FOG-1)']), verbo([interacts]), complemento([with, 'GATA-1', and, is, expressed, principally, in, hematopoietic, 'lineages,', whereas, 'FOG-2', is, expressed, predominantly, in, heart, and, brain])]). relacion([sujeto(['Although', gene]), verbo([targeting]), complemento([experiments, are, consistent, with, an, essential, role, for, 'FOG-1', as, an, activator, of, 'GATA-1', 'function,', reporter, assays, in, transfected, cells, indicate, that, 'FOG-1', and, 'FOG-2', can, act, as, repressors])]). relacion([sujeto(['We']), verbo([have]), complemento([cloned, a, 'Xenopus', laevis, homologue, of, 'FOG', that, is, structurally, most, similar, to, 'FOG-1,', but, is, expressed, predominantly, in, heart, and, 'brain,', as, well, as, the, ventral, blood, island, and, adult, spleen])]). relacion([sujeto(['Ectopic', expression, and, explant, assays, demonstrate, that, 'FOG', proteins, can]), verbo([act]), complemento([as, repressors, in, 'vivo,', in, part, through, interaction, with, the, transcriptional, 'co-repressor,', 'C-terminal', 'Binding', 'Protein', '(', 'CtBP)'])]). relacion([sujeto(['FOG', may]), verbo([regulate]), complemento([the, differentiation, of, red, blood, cells, by, modulating, expression, and, activity, of, 'GATA-1', and, 'GATA-2'])]). relacion([sujeto(['We', propose, that, the, 'FOG', proteins]), verbo([participate]), complemento([in, the, switch, from, progenitor, proliferation, to, red, blood, cell, maturation, and, differentiation])]). relacion([sujeto(['The', 'FLI-1', 'oncogene,', a, member, of, the, 'ETS', family, of, transcription, 'factors,', is]), verbo([associated]), complemento([with, both, normal, and, abnormal, hematopoietic, cell, growth, and, 'lineage-specific', differentiation])]). relacion([sujeto(['We']), verbo([have]), complemento([previously, shown, that, overexpression, of, 'FLI-1', in, pluripotent, human, hematopoietic, cells, leads, to, the, induction, of, a, megakaryocytic, phenotype])]). relacion([sujeto(['In', this]), verbo([report]), complemento([we, show, that, 'FLI-1', also, acts, as, an, inhibitor, of, erythroid, differentiation])]). relacion([sujeto(['Following', the, induction, of, erythroid, 'differentiation,', pluripotent, cells]), verbo([express]), complemento([reduced, levels, of, 'FLI-1'])]). relacion([sujeto(['The', ability, of, 'FLI-1', overexpressing, cells, to]), verbo([respond]), complemento([to, 'erythroid-specific', inducers, such, as, hemin, and, 'Ara-C', is, also, 'inhibited,', and, the, uninduced, cells, show, a, reduced, level, of, the, 'erythroid-associated', 'GATA-1', transcription, factor, mRNA])]). relacion([sujeto(['Furthermore,', expression, of, a, 'GATA-1', 'promoter-driven', reporter, construct, in, 'K562', cells, is]), verbo([inhibited]), complemento([by, 'co-transfection', with, a, construct, expressing, 'FLI-1'])]). relacion([sujeto(['Our', results, support, the, hypothesis, that, 'FLI-1', can]), verbo([act]), complemento([both, positively, and, negatively, in, the, regulation, of, hematopoietic, cell, 'differentiation,', and, that, inhibition, of, 'GATA-1', expression, may, contribute, to, 'FLI-1-mediated', inhibition, of, erythroid, differentiation])]). relacion([sujeto(['Eosinophil', granule, major, basic, protein, '(', 'MBP)', is]), verbo([expressed]), complemento([exclusively, in, eosinophils, and, basophils, in, hematopoietic, cells])]). relacion([sujeto(['Further', analysis, of, the, 'MBP', promoter, region, identified, a, 'C/EBP', '(', 'CCAAT/enhancer-binding', 'protein)', consensus]), verbo([binding]), complemento([site, 6, bp, upstream, of, the, functional, 'GATA-binding', site, in, the, 'MBP', gene])]). relacion([sujeto(['In', the, cell, line, 'HT93A,', which, is, capable, of, differentiating, towards, both, the, eosinophil, and, neutrophil, lineages, in, response, to, retinoic, acid, '(', 'RA),', 'C/EBPalpha', mRNA, expression]), verbo([decreased]), complemento([significantly, concomitant, with, eosinophilic, and, neutrophilic, 'differentiation,', whereas, 'C/EBPbeta', expression, was, markedly, increased])]). relacion([sujeto(['Electrophoretic', mobility, shift, assays, '(', 'EMSAs)', showed, that, recombinant, 'C/EBPbeta', protein, could]), verbo([bind]), complemento([to, the, potential, 'C/EBP-binding', site, '(', bp, -, 90, to, -, 82, ')', in, the, 'MBP', promoter])]). relacion([sujeto(['Furthermore,', we]), verbo([have]), complemento([demonstrated, that, both, 'C/EBPbeta', and, 'GATA-1', can, bind, simultaneously, to, the, 'C/EBP-', and, 'GATA-binding', sites, in, the, 'MBP', promoter])]). relacion([sujeto(['To', determine, the, functionality, of, both, the, 'C/EBP-', and, 'GATA-binding', 'sites,', we, analyzed, whether, 'C/EBPbeta', and, 'GATA-1', can]), verbo([stimulate]), complemento([the, 'MBP', promoter, in, the, 'C/EBPbeta', and, 'GATA-1', negative, 'Jurkat', 'T-cell', line])]). relacion([sujeto(['Cotransfection', with, 'C/EBPbeta', and, 'GATA-1', expression, vectors, produced, a, 5, -, fold]), verbo([increase]), complemento([compared, with, cotransfection, with, the, 'C/EBPbeta', or, 'GATA-1', expression, vectors, individually])]). relacion([sujeto(['Expression', of, 'FOG', '(', riend, 'ATA),', which]), verbo([binds]), complemento([to, 'GATA-1', and, acts, as, a, cofactor, for, 'GATA-binding', 'proteins,', decreased, transactivation, activity, of, 'GATA-1', for, the, 'MBP', promoter, in, a, 'dose-dependent', manner])]). relacion([sujeto(['Our', results]), verbo([provide]), complemento([the, first, evidence, that, both, 'GATA-1', and, 'C/EBPbeta', synergistically, transactivate, the, promoter, of, an, 'eosinophil-specific', granule, protein, gene, and, that, 'FOG', may, act, as, a, negative, cofactor, for, the, eosinophil, 'lineage,', unlike, its, positively, regulatory, function, for, the, erythroid, and, megakaryocyte, lineages])]). relacion([sujeto(['We']), verbo([have]), complemento([identified, a, novel, human, zinc, finger, 'protein,', 'hFOG-2,', which, is, related, to, but, distinct, from, the, murine, transcription, factor, 'Friend-of-GATA-1', '(', 'mFOG-1)'])]). relacion([sujeto(['A', murine, homologue, of, 'hFOG-2', was, also, identified, in, the, mouse]), verbo([expressed]), complemento([sequence, tag, data, 'banks,', indicating, that, a, family, of, 'FOG', genes, exists, in, mammals])]). relacion([sujeto(['hFOG-2', appears, to, be, widely, 'expressed,', while, 'mFOG-1', is]), verbo([expressed]), complemento([primarily, in, erythroid, and, megakaryocytic, cells, and, plays, a, fundamental, role, in, the, development, of, these, lineages])]). relacion([sujeto(['Sequencing', of, the, 'full-length', 'hFOG-2', cDNA, indicates, that, the, interaction, domains, for, transcription, factors, 'GATA-1', and, mCtBP2, are, both]), verbo([conserved]), complemento([and, we, have, shown, that, this, new, 'FOG', protein, also, physically, interacts, with, these, factors])]). relacion([sujeto(['We']), verbo([have]), complemento([demonstrated, that, 'hFOG-2,', like, 'mFOG-1,', can, act, in, concert, with, 'GATA-1', to, activate, gene, expression, from, the, p45, 'NF-E2', promoter, 'region,', but, that, it, can, also, act, to, repress, 'GATA-mediated', activation, of, additional, reporter, constructs])]). relacion([sujeto(['Finally,', we]), verbo([have]), complemento([identified, a, repression, domain, in, 'hFOG-2', and, show, that, repression, is, dependent, upon, the, integrity, of, the, mCtBP2, interaction, motif, 'Pro-Ile-Asp-Leu-Ser'])]). relacion([sujeto(['Malignant', transformation, usually]), verbo([inhibits]), complemento([terminal, cell, differentiation, but, the, precise, mechanisms, involved, are, not, understood])]). relacion([sujeto([1, is, a, 'hematopoietic-specific', 'Ets', family, transcription, factor, that, is]), verbo([required]), complemento([for, development, of, some, lymphoid, and, myeloid, lineages])]). relacion([sujeto([1, can, also]), verbo([act]), complemento([as, an, oncoprotein, as, activation, of, its, expression, in, erythroid, precursors, by, proviral, insertion, or, transgenesis, causes, erythroleukemias, in, mice])]). relacion([sujeto(['Restoration', of, terminal, differentiation, in, the, mouse, erythroleukemia, '(', 'MEL)', cells]), verbo([requires]), complemento([a, decline, in, the, level, of, 'PU'])]). relacion([sujeto(['We']), verbo([find]), complemento([that, 'PU'])]). relacion([sujeto([1]), verbo([interacts]), complemento([directly, with, 'GATA-1,', a, zinc, finger, transcription, factor, required, for, erythroid, differentiation])]). relacion([sujeto([1, and, 'GATA-1']), verbo([requires]), complemento([intact, 'DNA-binding', domains, in, both, proteins])]). relacion([sujeto(['Both', the, 'DNA']), verbo([binding]), complemento([and, transactivation, domains, of, 'PU'])]). relacion([sujeto([1, are]), verbo([required]), complemento([for, repression, and, both, domains, are, also, needed, to, block, terminal, differentiation, in, 'MEL', cells])]). relacion([sujeto(['Our', results, indicate, that, the, stoichiometry, of, directly]), verbo([interacting]), complemento([but, opposing, transcription, factors, may, be, a, crucial, determinant, governing, processes, of, normal, differentiation, and, malignant, transformation])]). relacion([sujeto(['Erythroid', 'Krüppel-like', factor, '(', 'EKLF)', is, a, zinc, finger, transcription, factor]), verbo([required]), complemento([for, 'beta-globin', gene, expression, and, is, implicated, as, one, of, the, key, factors, necessary, for, the, fetal, to, adult, switch, in, globin, gene, expression])]). relacion([sujeto(['In', an, effort, to, identify, factors]), verbo([involved]), complemento([in, the, expression, of, this, important, 'erythroid-specific', regulatory, 'protein,', we, have, isolated, the, mouse, 'EKLF', gene, and, systematically, analyzed, the, promoter, region])]). relacion([sujeto(['We', continued, the, expression, studies, in, erythroid, cells, and]), verbo([have]), complemento([identified, a, sequence, element, consisting, of, two, 'GATA', sites, flanking, an, 'E', box, motif])]). relacion([sujeto(['The', three, sites]), verbo([act]), complemento([in, concert, to, elevate, the, transcriptional, activity, of, the, 'EKLF', promoter])]). relacion([sujeto(['Each', site, is, essential, for, 'EKLF', expression, indicating, that, the, three]), verbo([binding]), complemento([sites, do, not, work, 'additively,', but, rather, function, as, a, unit])]). relacion([sujeto(['We', further, show, that, 'GATA-1']), verbo([binds]), complemento([to, the, two, 'GATA', sites, and, present, evidence, for, binding, of, another, factor, from, erythroid, cell, nuclear, extracts, to, the, 'E', box, motif])]). relacion([sujeto(['These', results, are, consistent, with, the, formation, of, a, quaternary, complex, composed, of, an, 'E', box, dimer, and, two, 'GATA-1', proteins]), verbo([binding]), complemento([at, a, combined, 'GATA-E', 'box-GATA', activator, element, in, the, distal, 'EKLF', promoter])]). relacion([sujeto(['It']), verbo([has]), complemento([been, postulated, that, regulation, occurs, through, physical, interactions, between, factors, bound, to, these, 'elements,', which, are, located, at, considerable, distances, from, each, other])]). relacion([sujeto(['To', identify, the, elements]), verbo([required]), complemento([for, 'promoter-enhancer', interactions, from, a, 'distance,', we, have, investigated, the, expression, of, the, 'wild-type,', 'truncated,', and, mutated, 'gamma-globin', promoters, linked, to, the, 5, '\'', 'HS2', enhancer])]). relacion([sujeto(['We', show, that, in, 'K562', 'cells,', 5, '\'', 'HS2']), verbo([increases]), complemento([activity, approximately, 20, -, fold, from, both, a, 'wild-type', and, truncated, '(', -, 135, -, -, &, 'gt;', +, 25, ')', gamma, promoter, and, that, truncation, or, 'site-directed', mutagenesis, of, the, tandem, 'CCAAT', boxes, eliminated, the, enhancement, by, 5, '\'', 'HS2'])]). relacion([sujeto(['Mutation', of, the, 'gamma-globin', gene, promoter, 'GATA-1']), verbo([binding]), complemento([sites, did, not, decrease, either, promoter, strength, or, enhancement, of, activity, by, 5, '\'', 'HS2'])]). relacion([sujeto(['To', determine, if]), verbo([enhanced]), complemento([expression, of, 'gamma-globin', gene, promoters, carrying, mutations, associated, with, hereditary, persistence, of, fetal, hemoglobin, '(', 'HPFH)', was, due, to, greater, interactions, with, 'enhancers,', we, linked, these, 'HPFH', 'gamma-globin', gene, promoters, to, 5, '\'', 'HS2', and, demonstrated, a, twofold, to, threefold, higher, expression, than, the, corresponding, 'wild-type', promoter, plus, enhancer, in, 'MEL', cells])]). relacion([sujeto(['Addition', of, the, 'Agamma-globin', gene, 3, '\'', enhancer, to, a, plasmid, containing, the, 'gamma-globin', gene, promoter, and, 5, '\'', 'HS2', did, not, further]), verbo([enhance]), complemento([promoter, strength])]). relacion([sujeto(['Furthermore,', we]), verbo([have]), complemento([demonstrated, that, the, previously, identified, core, 5, '\'', 'HS2', enhancer, '(', 46, -, bp, tandem, 'AP-1/NF-E2', 'sites)', increased, expression, only, when, located, 5, '\'', ',', but, not, 3, '\'', ',', to, the, 'gamma-globin-luciferase', reporter, 'gene,', suggesting, that, its, enhancer, effect, is, not, by, 'DNA', looping])]). relacion([sujeto(['Our', results]), verbo([suggest]), complemento([that, 'CCAAT', 'boxes,', but, not, 'GATA', or, 'CACCC', binding, 'sites,', are, required, for, interaction, between, the, 'gamma-globin', promoter, and, the, 'LCR/5\'HS2', and, that, regulatory, elements, in, addition, to, the, core, enhancer, may, be, required, for, the, enhancer, to, act, from, a, distance])]). relacion([sujeto(['In', an]), verbo([increasing]), complemento([number, of, hematopoietic, cytokine, receptor, systems, '(', 'T-cell', 'receptor,', 'B-cell', 'receptor,', and, macrophage, 'colony-stimulating', 'factor,', stem, cell, 'factor,', 'interleukin-3,', and, erythropoietin, '[', 'EPO]', 'receptors),', inhibitory, roles, for, the, protein, tyrosine, phosphatase, hematopoietic, cell, phosphatase, '(', 'HCP;', 'SHPTP1,', 'PTP1C,', and, 'SHP1)', have, been, defined, in, proliferative, signaling])]). relacion([sujeto(['However,', evidence, exists, to]), verbo([suggest]), complemento([that, 'HCP', also, may, exert, important, effects, on, blood, cell, differentiation])]). relacion([sujeto(['To', investigate, possible, roles, for, 'HCP', during, late, erythroid, 'differentiation,', effects, of, manipulating, 'HCP', expression, or, recruitment, on, 'EPO-induced', hemoglobinization, in, erythroleukemic, 'SKT6', cells]), verbo([have]), complemento([been, investigated])]). relacion([sujeto(['No', effects, of, 'EPO', on, levels, of, 'HCP,', 'Syp,', 'Stat5,', the, 'EPO', 'receptor,', or, 'GATA-1', expression, were, observed, during]), verbo([induced]), complemento([differentiation])]). relacion([sujeto(['However,', the, tyrosine, phosphorylation, of, 'JAK2,', the, 'EPO', 'receptor,', and, 'Stat5', was, efficiently, 'activated,', and, 'HCP', was, observed, to]), verbo([associate]), complemento([constitutively, with, the, 'EPO', receptor, in, this, 'differentiation-specific', system])]). relacion([sujeto(['In', studies, of, 'HCP', 'function,', inhibition, of, 'HCP', expression, by, antisense, oligonucleotides]), verbo([enhanced]), complemento(['hemoglobinization,', whereas, the, enforced, ectopic, expression, of, 'wild-type', '(', 'wt)', 'HCP', markedly, inhibited, 'EPO-induced', globin, expression, and, 'Stat5', activation])]). relacion([sujeto(['Based', on, these, 'findings,', epidermal, growth, factor, '(', 'EGF)', 'receptor/EPO', receptor, chimeras, containing, either, the, wt, 'EPO', receptor, cytoplasmic, domain, '(', 'EECA)', or, a, derived, 'HCP']), verbo([binding]), complemento([site, mutant, '(', 'EECA-Y429,431F)', were, expressed, in, 'SKT6', 'cells,', and, their, abilities, to, mediate, differentiation, were, assayed])]). relacion([sujeto(['Each', chimera, supported, 'EGF-induced', 'hemoglobinization,', but, efficiencies, for, 'EECA-Y429,431F', were]), verbo([enhanced]), complemento([400, '%', to, 500, '%'])]). relacion([sujeto(['In', normal, erythroid, progenitor, 'cells,', 'HCP', may]), verbo([act]), complemento([to, prevent, premature, commitment, to, terminal, differentiation])]). relacion([sujeto(['Aclacinomycin', '(', 'ACLA)', and, doxorubicin, '(', 'DOX)', were, used, at, subtoxic, concentrations, to]), verbo([induce]), complemento([erythroid, differentiation, in, the, human, leukemic, cell, line, 'K562'])]). relacion([sujeto(['Cell', hemoglobinization, was, accompanied, by, the]), verbo([increased]), complemento([expression, of, genes, encoding, 'gamma-globin', and, porphobilinogen, deaminase, '(', 'PBGD),', an, enzyme, of, heme, synthesis])]). relacion([sujeto(['By', using, 'run-on', 'assays,', 'ACLA', was, shown, to]), verbo([induce]), complemento([an, enhancement, of, the, transcription, of, erythroid, 'genes,', including, 'gamma-globin,', 'PBGD,', erythropoietin, 'receptor,', and, 'GATA-1', transcription, factor])]). relacion([sujeto(['In', 'addition,', inhibition, of, mRNA, synthesis, with, actinomycin, 'D', indicated, that, 'DOX']), verbo([induced]), complemento([an, increased, stability, of, 'PBGD', and, 'GATA-1', 'mRNAs,', whereas, 'ACLA', did, not, affect, the, 'half-lives', of, these, mRNAs])]). relacion([sujeto(['Because', the]), verbo([increase]), complemento([in, erythroid, mRNA, 'steady-state', level, in, 'anthracycline-treated', cells, was, inhibited, by, 'cycloheximide,', this, suggests, that, transcriptional, activation, in, 'ACLA-treated', cells, and, mRNA, stabilization, in, 'DOX-treated', cells, were, dependent, on, de, novo, protein, synthesis])]). relacion([sujeto(['Finally,', 'GATA-1', protein, level, was, shown, to, be]), verbo([increased]), complemento([in, 'ACLA-treated', but, not, in, 'DOX-treated', cells])]). relacion([sujeto(['These', two, 'anthracyclines,', although, closely, related, in, their, 'structures,', appeared, to]), verbo([act]), complemento([as, differentiation, inducers, by, distinct, mechanisms])]). relacion([sujeto(['Indeed,', erythroid, gene, expression, was, demonstrated, to, be]), verbo([regulated]), complemento([transcriptionally, by, 'ACLA', and, mainly, posttranscriptionally, by, 'DOX'])]). relacion([sujeto(['EVI1', is, a, zinc, finger, oncoprotein, that]), verbo([binds]), complemento([via, fingers, 1, -, 7, to, the, sequence, 'GACAAGATAA'])]). relacion([sujeto(['The']), verbo([target]), complemento([genes, on, which, 'EVI1', acts, are, unknown])]). relacion([sujeto(['This']), verbo([binding]), complemento([motif, overlaps, with, that, for, the, 'GATA', transcription, 'factors,', '(', 'T/A)GATA(A/G),', and, 'GATA-1', can, bind, to, and, activate, transcription, via, a, 'GACAAGATAA', motif])]). relacion([sujeto(['The', possibility]), verbo([has]), complemento([been, raised, 'that,', when, overexpressed, in, 'leukemogenesis,', 'EVI1', may, function, by, interfering, with, the, 'differentiation-promoting', action, of, 'GATA', factors])]). relacion([sujeto(['To', explore, 'this,', we]), verbo([have]), complemento([assessed, the, affinity, of, 'EVI1', for, the, 'GATA', binding, sites, derived, from, 'erythroid-specific', 'GATA-1', target, 'genes,', and, found, only, low, affinity, interactions])]). relacion([sujeto(['We', examined, the, contacts, between, 'EVI1', and, 'DNA', by, methylation, interference, 'studies,', which, revealed, extensive, contacts, between, 'EVI1', and, its]), verbo([binding]), complemento([site])]). relacion([sujeto(['The', importance, of, the, contacts, for, high, affinity]), verbo([binding]), complemento([was, shown, by, in, vitro, quantitative, gel, shift, studies, and, in, vivo, cotransfection, studies])]). relacion([sujeto(['To', examine, what, types, of, sequences, from, mouse, genomic, 'DNA']), verbo([bind]), complemento([to, 'EVI1,', we, isolated, and, sequenced, five, 'EVI1-binding', 'fragments,', and, each, showed, the, 'GACAAGATA', site])]). relacion([sujeto(['The', data, presented, contribute, to, our, knowledge, of, the]), verbo([binding]), complemento([specificity, of, 'EVI1,', and, yield, a, clearer, picture, of, what, sequences, 'can,', and, 'cannot,', act, as, targets, for, 'EVI1', action])]). relacion([sujeto(['The', transcriptional, 'activator,', 'Tax,', of, human, 'T-cell', leukemia, virus, '(', 'HTLV-I)']), verbo([has]), complemento([been, considered, to, interact, with, cellular, proteins, to, act, on, target, enhancer, motifs])]). relacion([sujeto(['Using', oligodeoxyribonucleotides, containing, the, 'tax-responsive', element, '(', 'TAXRE)', of, the, 'HTLV-I', 'enhancer,', we]), verbo([have]), complemento([cloned, multiple, cDNAs, coding, for, 'TAXRE-binding', proteins, '(', 'TAXREB),', and, determined, the, cDNA, and, the, deduced, 200, -, 'amino-acid', sequences, for, 'TAXREB302'])]). relacion([sujeto(['The', recombinant, protein]), verbo([binds]), complemento([to, the, enhancer, 'DNA', by, specific, interaction, to, the, 'CRE-like', sequence])]). relacion([sujeto(['TAXREB302', does, not]), verbo([have]), complemento([structural, features, common, to, the, 'CRE-binding', protein, or, activating, transcription, factor, '(', 'CREB/ATF)', 'family,', but, has, homology, to, chicken, erythroid, transcription, factor, '(', 'Eryf1', or, 'GATA-1),', suggesting, a, possible, 'protein-protein', interaction])]). relacion([sujeto(['The', human, glycoprotein, 'IIB', '(', 'GPIIB)', gene, is]), verbo([expressed]), complemento([only, in, 'megakaryocytes,', and, its, promoter, displays, cell, type, specificity])]). relacion([sujeto(['We', show, that, this, specificity]), verbo([involved]), complemento([two, 'cis-acting', sequences])]). relacion([sujeto(['The', first, 'one,', located, at, -, 55, ',', contains, a, 'GATA']), verbo([binding]), complemento([site])]). relacion([sujeto(['Point', mutations, that, abolish, protein]), verbo([binding]), complemento([on, this, site, decrease, the, activity, of, the, 'GPIIB', promoter, but, do, not, affect, its, tissue, specificity])]). relacion([sujeto(['The', second, 'one,', located, at, -, 40, ',', contains, an, 'Ets', consensus, 'sequence,', and, we, show, that, 'Ets-1', or, 'Ets-2', protein, can]), verbo([interact]), complemento([with, this, -, 40, 'GPIIB', sequence])]). relacion([sujeto(['Point', mutations, that, impair, 'Ets']), verbo([binding]), complemento([decrease, the, activity, of, the, 'GPIIB', promoter, to, the, same, extent, as, do, mutations, that, abolish, 'GATA', binding])]). relacion([sujeto(['A', 'GPIIB', 40, -, bp, 'DNA', fragment, containing, the, 'GATA', and, 'Ets']), verbo([binding]), complemento([sites, can, confer, activity, to, a, heterologous, promoter, in, megakaryocytic, cells])]). relacion([sujeto(['This', activity, is, independent, of, the, 'GPIIB', 'DNA', fragment, 'orientation,', and, mutations, on, each]), verbo([binding]), complemento([site, result, in, decreased, activity])]). relacion([sujeto(['Using', cotransfection, 'assays,', we, show, that, 'c-Ets-1', and, human, 'GATA1', can, transactive, the, 'GPIIB', promoter, in, 'HeLa', cells, and, can]), verbo([act]), complemento([additively])]). relacion([sujeto(['Northern', '(', 'RNA)', blot, analysis, indicates, that, the, 'ets-1', mRNA, level, is]), verbo([increased]), complemento([during, 'megakaryocyte-induced', differentiation, of, 'erythrocytic/megakaryocytic', cell, lines])]). relacion([sujeto(['Gel', retardation, assays, show, that, the, same, 'GATA-Ets', association, is]), verbo([found]), complemento([in, the, human, 'GPIIB', enhancer, and, the, rat, platelet, factor, 4, 'promoter,', the, other, two, characterized, regulatory, regions, of, 'megakaryocyte-specific', genes])]). relacion([sujeto(['In', normal, humans, the, fetal, 'stage-specific', 'gamma-globin', genes, are, silenced, after, birth, and, not]), verbo([expressed]), complemento([in, the, adult])]). relacion([sujeto(['One', class, of, mutations, is]), verbo([associated]), complemento([with, point, mutations, in, the, promoter, of, the, 'gamma-globin', genes, '(', 'non-deletion', 'HPFH),', whereas, others, seem, to, be, caused, by, large, deletions, 3, '\'', to, the, 'gamma-globin', genes])]). relacion([sujeto(['To', test, whether, the, point, mutation]), verbo([found]), complemento([in, the, 'Greek', 'non-deletion', 'HPFH', '(', guanine, to, adenine, at, nucleotide, position, -, 117, ')', is, the, cause, of, the, raised, 'gamma-globin', levels, in, the, adult, stage, and, is, not, just, a, linked, 'polymorphism,', we, engineered, this, mutation, into, a, 'gamma-globin', gene])]). relacion([sujeto(['When', this, gene, was, introduced, into, 'mice,', the, presence, of, the, -, 117, mutation, results, in, persistence, of, 'gamma-globin', expression, at, a, high, level, and, a, concomitant]), verbo([decrease]), complemento([in, 'beta-globin', expression, in, fetal, and, adult, mice])]). relacion([sujeto(['We', show, that, these, changes, correlate, with, the]), verbo([loss]), complemento([of, binding, of, the, transcription, factor, 'GATA1', to, the, 'gamma-globin', 'promoter,', suggesting, that, it, may, act, as, a, negative, regulator, of, the, 'gamma-globin', gene, in, adults])]). relacion([sujeto(['Lysophosphatidic', acid, '(', 'LPA),', a, lipid, growth, factor, was, previously, shown, to, be, a, regulator, for, erythropoietic, process, through]), verbo([activating]), complemento(['LPA', receptor, 3, '(', 'LPA3)'])]). relacion([sujeto(['We', demonstrated, that, 'K562', cells]), verbo([express]), complemento([both, 'LPA2', and, 'LPA3,', and, the, expression, levels, of, 'LPA2', are, higher, than, 'LPA3'])]). relacion([sujeto(['Treatment', with, phorbol, 12, -, myristate, 13, -, 'acetate,', a, commonly, used, inducer, of, 'megakaryopoiesis,', reciprocally]), verbo([regulates]), complemento([the, expressions, of, 'LPA2', and, 'LPA3'])]). relacion([sujeto(['By', pharmacological, blockers, and, knockdown, 'experiments,', we, showed, that, activation, of, 'LPA2']), verbo([suppresses]), complemento(['whereas,', 'LPA3', promotes, megakaryocytic, differentiation, in, 'K562'])]). relacion([sujeto(['Furthermore,', the, hematopoietic, transcriptional, factors, 'GATA-1', and, 'FLI-1,', appear, to, be]), verbo([involved]), complemento([in, these, regulatory, mechanisms])]). relacion([sujeto(['Taken', 'together,', our, results]), verbo([suggested]), complemento([that, 'LPA2', and, 'LPA3', may, function, as, a, molecular, switch, and, play, opposing, roles, during, megakaryopoiesis, of, 'K562', cells])]). relacion([sujeto(['We', observed, 'up-regulation', of, 'ZNF16', during, erythroid, and, megakaryocytic, differentiation, of, the, 'CD34+', 'HSPCs,', and, demonstrated, that, 'ZNF16']), verbo([promotes]), complemento([erythroid, and, megakaryocytic, differentiation, by, 'gain-of-function', and, 'loss-of-function', experiments])]). relacion([sujeto(['Using', a, luciferase, reporter, and, 'ChIP', assays, 'ZNF16', was, demonstrated, to]), verbo([bind]), complemento([to, the, 'c-KIT', gene, promoter, and, inhibit, its, expression, in, 'K562', cells])]). relacion([sujeto(['Significantly']), verbo([decreased]), complemento([levels, of, the, 'c-Kit', protein, were, observed, following, erythroid, and, megakaryocytic, differentiation, of, 'K562', and, 'CD34+', cells])]). relacion([sujeto(['The', knockdown, of, 'c-KIT', partially, rescued, the, differentiation, inhibition]), verbo([caused]), complemento([by, 'ZNF16', knockdown])]). relacion([sujeto(['The', aim, of, this, study, was, to, evaluate, cell, maturation, and, the, platelet, production, capacity, of, the, megakaryoblastic, 'DAMI', cell, 'line,', to, characterize, 'platelet-like', particles, produced, and, to, investigate, the, mechanisms]), verbo([involved]), complemento([in, their, production])]). relacion([sujeto(['DAMI', cell, maturation, was]), verbo([induced]), complemento([by, phorbol, myristate, acetate, '(', 'PMA)', and, thrombopoietin, '(', 'TPO)'])]). relacion([sujeto(['We']), verbo([found]), complemento([that, stimulation, of, 'DAMI', cells, with, high, concentration, of, 'PMA', and, 'TPO', induced, the, expression, of, transcription, factors, 'GATA-1', and, 'Fli-1', followed, by, an, increase, in, the, isoform, a, of, 'NF-E2'])]). relacion([sujeto(['Mature', 'DAMI', cells, give, rise, to, extensions, resembling, proplatelets, and, 'later,', produce, 'platelet-like', particles]), verbo([expressing]), complemento(['GPIIb', and, 'GPIb', on, their, surface, and, containing, dense, and, alpha, 'granules,', which, were, confirmed, by, electron, microscopy])]). relacion([sujeto(['Platelet', functionality, was, demonstrated, by, the]), verbo([increase]), complemento([in, 'P-selectin', membrane, expression, after, thrombin, stimulation, and, by, their, ability, to, spread, on, fibrinogen, matrices])]). relacion([sujeto(['DAMI', cell, line]), verbo([induced]), complemento([to, differentiate, into, mature, megakaryocytes, is, able, to, produce, functional, platelets, providing, a, suitable, model, to, study, the, mechanisms, involved, in, platelet, generation])]). relacion([sujeto(['Specific', interactions, of, transcription, factors, '(', 'TFs)', with, their]), verbo([targets]), complemento([are, crucial, for, specifying, gene, expression, programs, during, cell, differentiation])]). relacion([sujeto(['How', specificity, is]), verbo([maintained]), complemento([despite, limited, selectivity, of, individual, 'TF-DNA', interactions, is, not, fully, understood])]). relacion([sujeto(['We', used, megakaryocytic, cell, lines, to, characterize, the, network, of, 'RUNX1']), verbo([targets]), complemento([and, cooperating, 'TFs', in, differentiating, megakaryocytes, and, demonstrated, how, dynamic, partnerships, between, 'RUNX1', and, cooperating, 'TFs', facilitated, regulatory, plasticity, and, specificity, during, this, process])]). relacion([sujeto(['After', differentiation, 'onset,', 'RUNX1', directly]), verbo([activated]), complemento([a, large, number, of, genes, through, interaction, with, preexisting, and, de, novo, binding, sites])]). relacion([sujeto(['A', significant, number, of, these, de, novo]), verbo([bound]), complemento([sites, lacked, 'RUNX', motif, but, were, occupied, by, 'AP-1', 'TFs'])]). relacion([sujeto(['Reciprocally,', 'AP-1', 'TFs', were, 'up-regulated', by, 'RUNX1', after, 12, -, 'O-tetradecanoylphorbol-13-acetate', induction, and]), verbo([recruited]), complemento([to, 'RUNX1-occupied', sites, lacking, 'AP-1', motifs])]). relacion([sujeto(['The', findings]), verbo([suggest]), complemento([that, in, differentiating, megakaryocytic, cell, 'lines,', 'RUNX1', cooperates, with, 'GATA1,', 'AP-1,', and, 'ETS', to, orchestrate, 'cell-specific', transcription, programs, through, dynamic, 'TF', partnerships])]). relacion([sujeto(['However,', the, molecular, mechanisms]), verbo([involved]), complemento([in, leukemia, cell, differentiation, have, not, been, fully, elucidated])]). relacion([sujeto(['Interleukin', 6, '(', 'IL-6)', is, a, pleiotropic, cytokine]), verbo([acting]), complemento([on, a, variety, of, cell, 'types,', and, plays, important, roles, in, hematopoiesis])]). relacion([sujeto(['GATA']), verbo([binding]), complemento([protein, 1, '(', 'GATA-1)', is, an, important, transcription, factor, involved, in, either, megakaryocytic, or, erythrocytic, differentiation])]). relacion([sujeto(['Herein', we]), verbo([report]), complemento([that, 'Rab7b,', a, late, 'endosome/lysosome-localized', myeloid, small, 'GTPase,', promotes, 'phorbol-12-myristate-13-acetate', '(', 'PMA)-induced', megakaryocytic, differentiation, by, increasing, nuclear, factor, κB, '(', 'NF-κB)-dependent', 'IL-6', production, and, subsequently, enhancing, the, association, of, activated, signal, transducer, and, activator, of, transcription, 3, '(', 'STAT3)', with, 'GATA-1'])]). relacion([sujeto(['We']), verbo([find]), complemento([that, 'Rab7b', can, potentiate, 'PMA-induced', upregulation, of, megakaryocytic, 'markers,', production, of, 'IL-6,', and, activation, of, 'NF-κB'])]). relacion([sujeto(['Therefore,', our, data]), verbo([suggest]), complemento([that, 'Rab7b', may, play, important, roles, in, megakaryopoiesis, by, activating, 'NF-κB', and, promoting, 'IL-6', production])]). relacion([sujeto(['Our', study, also, indicates, that, the, 'IL-6-induced', association, of, 'STAT3', with, 'GATA-1', may]), verbo([regulate]), complemento([megakaryocytic, differentiation])]). relacion([sujeto(['EDAG,', a, hematopoietic, 'tissue-specific', 'protein,', is]), verbo([involved]), complemento([in, the, regulation, of, 'proliferation,', differentiation, and, apoptosis, of, hematopoietic, cells])]). relacion([sujeto(['By', 'oligonucleotide-directed', 'mutagenesis,', 'EMSA,', 'ChIP', and, transient, transfection, 'assays,', we]), verbo([found]), complemento([that, two, tandem, repeat, 'GATA-1', sites, in, the, promoter, of, 'EDAG', gene, played, an, important, role, in, the, 'PMA-mediated', 'down-regulation', of, the, 'EDAG', gene, expression, in, 'K562', cells])]). relacion([sujeto(['Overexpression', of, 'EDAG', in, 'K562', cells]), verbo([inhibited]), complemento([the, megakaryocytic, differentiation, induced, by, 'PMA', which, raised, the, interesting, possibility, that, 'PMA', induced, 'K562', cells, differentiation, toward, megakaryocytic, phenotype, 'through,', at, least, in, 'part,', the, inhibition, of, 'EDAG', expression])]). relacion([sujeto(['In', vivo, analysis, confirmed, that, 'EDAG', was, highly]), verbo([expressed]), complemento([in, primitive, progenitor, cells, and, 'down-regulated', in, megakaryocytes, which, was, consistent, with, the, expression, pattern, of, 'GATA-1'])]). relacion([sujeto(['Furthermore,', 'PKC', and, 'MAPK', specific, inhibitors, treatment, attenuated, the, 'down-regulation', of, 'EDAG']), verbo([induced]), complemento([by, 'PMA'])]). relacion([sujeto(['Taken', 'together,', these, results]), verbo([suggest]), complemento([that, the, inhibition, of, the, 'EDAG', gene, by, 'PMA', is, mediated, through, 'down-regulation', of, transcription, factor, 'GATA-1', and, involved, the, 'PKC/MAPK', signaling, pathway])]). relacion([sujeto(['Activation', of, 'Notch', signals, by, the, intracellular, 'Notch1', or, an, 'estradiol-inducible', form, of, 'Notch1/ER']), verbo([suppressed]), complemento([the, expression, of, the, erythroid, marker, glycophorin, 'A', in, an, 'erythroid/megakaryocytic', cell, line, 'K562'])]). relacion([sujeto(['Although', 'Mock-transfected', 'K562', cells, underwent, megakaryocytic, differentiation, in, response, to, 12, -, 'O-tetradecanoylphorbol-13-acetate', '(', 'TPA),', 'estradiol-activated', 'Notch1/ER']), verbo([induced]), complemento([apoptosis, during, 'TPA', treatment, in, the, 'transfectant,', which, was, accompanied, by, the, reduced, expression, of, an, antiapoptotic, molecule, 'Bcl-XL'])]). relacion([sujeto(['Even', when, apoptosis, was]), verbo([prevented]), complemento([by, the, overexpression, of, 'Bcl-XL,', activated, 'Notch', signals, still, inhibited, 'TPA-induced', megakaryocytic, differentiation])]). relacion([sujeto(['As', for, this, 'mechanism,', 'Notch1/recombination', signal]), verbo([binding]), complemento([protein, 'J-kappa-induced', 'HES1', but, not, 'HES5', was, found, to, inhibit, the, function, of, an, 'erythroid/megakaryocytic', 'lineage-specific', transcription, factor, 'GATA-1'])]). relacion([sujeto(['Although', 'HES1', did, not, affect, the, 'DNA']), verbo([binding]), complemento([activity, of, 'GATA-1', in, gel, shift, and, chromatin, immunoprecipitation, 'assays,', it, directly, bound, to, 'GATA-1', and, dissociated, a, critical, transcriptional, 'cofactor,', 'p300,', from, 'GATA-1'])]). relacion([sujeto(['Furthermore,', overexpressed, 'HES1']), verbo([inhibited]), complemento([the, development, of, erythroid, and, megakaryocytic, cells, in, colony, assays])]). relacion([sujeto(['Also,', the, 'Notch', ligand, 'Jagged1']), verbo([expressed]), complemento([on, 'NIH3T3', cells, suppressed, the, development, of, erythroid, and, megakaryocytic, cells, from, cocultured, 'Lin-Sca-1+', hematopoietic, 'stem/progenitor', cells])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, 'Notch1', inhibits, the, development, of, 'erythroid/megakaryocytic', cells, by, suppressing, 'GATA-1', activity, through, 'HES1'])]). relacion([sujeto(['In', this, 'study,', the, effect, of, tellimagrandin, 'I', on, chemically]), verbo([induced]), complemento([erythroid, and, megakaryocytic, differentiation, was, investigated, using, 'K562', cells, as, differentiation, model])]). relacion([sujeto(['It', was]), verbo([found]), complemento([that, tellimagrandin, 'I', not, only, inhibited, the, hemoglobin, synthesis, in, butyric, acid, '(', 'BA)-', and, 'hemin-induced', 'K562', cells, with, 'IC50', of, 3, and, 40, 'microM,', 'respectively,', but, also, inhibited, other, erythroid, differentiation, marker, including, acetylcholinesterase, '(', 'AChE)', and, glycophorin, 'A', '(', 'GPA)', in, 'BA-induced', 'K562', cells])]). relacion([sujeto(['Tellimagrandin', 'I', also]), verbo([inhibited]), complemento([12, -, 'O-tetradecanoylphorbol-13-acetate', '(', 'TPA)-induced', expression, of, 'CD61', 'protein,', a, megakaryocytic, marker])]). relacion([sujeto(['RT-PCR', analysis, showed, that, tellimagrandin, 'I']), verbo([decreased]), complemento([the, expression, of, erythroid, genes, '(', 'gamma-globin', and, porphobilinogen, deaminase, '(', 'PBGD))', and, related, transcription, factors, '(', 'GATA-1', and, 'NF-E2)', in, 'BA-induced', 'K562', 'cells,', whereas, tellimagrandin, 'I', induced, the, overexpresison, of, 'GATA-2', transcription, factor, that, played, negative, regulation, on, erythroid, differentiation])]). relacion([sujeto(['These', results, indicated, that, tellimagrandin, 'I', had, inhibitory, effects, on, erythroid, and, megakaryocytic, 'differentiation,', which]), verbo([suggested]), complemento([that, tannins, like, tellimagrandin, 'I', might, influence, the, 'anti-tumor', efficiency, of, some, drugs, and, the, hematopoiesis, processes])]). relacion([sujeto(['Results', show, that, 'GSTP1-1', mRNA, as, well, as, protein, expressions, are]), verbo([increased]), complemento([during, 'Aclarubicin', '(', 'Acla)-', and, 'Doxorubicin', '(', 'Dox)-induced', erythroid, differentiation, of, human, 'K562', cells])]). relacion([sujeto(['In', 'contrast,', during, megakaryocytic, differentiation, by, 12, -, 'O-tetradecanoyl', phorbol, 13, -, acetate, '(', 'TPA),', 'GSTP1-1', expression]), verbo([decreased]), complemento([at, both, mRNA, and, protein, levels])]). relacion([sujeto(['In', order, to, clarify, the, molecular, mechanisms]), verbo([leading]), complemento([to, these, 'variations,', we, identified, a, 'GATA', sequence, located, at, -, 1208, relative, to, the, transcriptional, start, site, of, the, 'GSTP1-1', promoter])]). relacion([sujeto(['By', gel, 'shift,', 'competition,', and, supershift, analyses, we, show, here, the, specificity, of, the, 'GATA-1']), verbo([binding]), complemento([regulated, by, both, anthracyclines, and, 'TPA'])]). relacion([sujeto(['In', cell, lines, with, properties, of, 'AML', 'M6/M7', '(', 'K562', and, 'CMK),', differentiation, towards, megakaryopoietic, and, erythropoietic, phenotypes, can, be]), verbo([induced]), complemento([in, vitro])]). relacion([sujeto(['Recently,', mutations, of, the, 'GATA1', transcription, factor]), verbo([have]), complemento([been, identified, in, the, megakaryoblastic, leukemia, of, 'Down', syndrome])]). relacion([sujeto(['In', 'vitro,', terminal, differentiation, towards, a, 'megakaryocyte-like', phenotype, could, be]), verbo([induced]), complemento([by, phorbol, myristate, acetate, '(', 'PMA),', with, typical, morphological, 'features,', upregulation, of, 'platelet-specific', and, downregulation, of, erythroid, 'antigens,', going, along, with, downregulation, of, 'c-myc'])]). relacion([sujeto(['Whether', spontaneous, resolution, of, 'TMD', is, a, process, due, to, terminal, differentiation, is, still, 'open;', 'however,', here, we, give, evidence, that, in, vitro, differentiation, can, be]), verbo([induced]), complemento([even, in, blasts, deriving, from, an, overt, 'AML', 'French-American-British', '(', 'FAB)', 'M7', after, 'TMD'])]). relacion([sujeto(['The', convertase, furin, is]), verbo([involved]), complemento([in, the, maturation, of, key, 'growth/aggregation', mediators, synthesized, by, the, platelet, 'producers,', 'megakaryocytes,', but, the, regulation, of, furin, in, these, cells, remains, unknown])]). relacion([sujeto(['Computer-assisted', search, of, the, furin, promoter, sequence, revealed, multiple, potential]), verbo([binding]), complemento([motifs, for, 'GATA-1,', suggesting, that, furin, is, expressed, and, regulated, in, these, cells])]). relacion([sujeto(['Using', megakaryoblastic, 'Dami', 'cells,', we, observed, that, fur, mRNA, expression]), verbo([increased]), complemento([gradually, on, phorbol, 12, -, myristate, 13, -, 'acetate-induced', 'differentiation,', reaching, maximum, levels, '(', 8.3, -, fold, 'increase)', at, 10, days])]). relacion([sujeto(['Coexpression', of, 'GATA-1', and, its, 'comodulator,', 'Friend', of, 'GATA-1', '(', 'FOG-1),', resulted, in, a, cooperative]), verbo([increase]), complemento([in, 'P1', activity])]). relacion([sujeto(['Point', mutation, of, each, of, the, 2, motifs, indicated, that, the, intactness, of, the, first, 'GATA', site, is]), verbo([required]), complemento([for, full, basal, and, 'GATA-1-stimulated', promoter, activity])]). relacion([sujeto(['Finally,', the, inhibition, of, furin, activity, through, gene, transfer, of, the, inhibitor, 'alpha1-AT-PDX']), verbo([led]), complemento([to, a, block, in, maturation, of, the, furin, substrates, transforming, growth, 'factor-beta1', and, 'platelet-derived', growth, factor])]). relacion([sujeto(['They', also]), verbo([suggest]), complemento([that, proper, regulation, of, the, fur, gene, in, megakaryocytes, has, an, impact, on, the, activation, of, furin, substrates, involved, in, megakaryocyte, maturation, and, platelet, functions])]). relacion([sujeto(['Mona/grb2', related, adapter, downstream, of, shc, is, a, molecular, adapter]), verbo([expressed]), complemento([in, 'platelets,', 'T', lymphocytes, and, myelomonocytic, cells])]). relacion([sujeto(['Using', human, hematopoietic, cell, 'lines,', we]), verbo([have]), complemento([previously, shown, that, 'lineage-specific', 'Mona', expression, is, achieved, through, the, production, of, two, transcripts, '(', named, 1, 'A', and, 1, 'B)', differing, by, their, 5, '\'', untranslated, region, '(', 5, '\'', 'UTR)'])]). relacion([sujeto(['Thus,', platelets, and, megakaryocytic, cell, lines, 'K562', and, 'HEL', '(', 'Human', 'Erythro-Leukemia)', specifically]), verbo([express]), complemento([1, 'B', messenger, 'RNA', '(', 'mRNA)'])]). relacion([sujeto(['We']), verbo([report]), complemento([here, characterization, of, the, '(', -, 2031, /, +, 72, ')', genomic, region, relative, to, the, putative, transcription, start, site, of, 1, 'B', mRNA])]). relacion([sujeto(['We', show, this, region, is, sufficient, to]), verbo([ensure]), complemento([specific, reporter, gene, expression, in, megakaryocytic, cell, 'lines,', and, that, most, promoter, activity, is, contained, in, the, '(', -, 225, /, +, 72, ')', fragment])]). relacion([sujeto(['Electro-mobility', shift, assay, and, mutational, analyses, indicated, that, 'GATA-1', and, a, yet, unidentified, 'E-26', family, member, transcription, factor, are]), verbo([required]), complemento([for, 1, 'B', '(', -, 2031, /, +, 72, ')', promoter, activity])]). relacion([sujeto(['Recently', we, observed, that, the, transcription, factors, 'Sp1', and, 'Sp3']), verbo([bind]), complemento([to, the, 'CTCCTCCTC', sequence, located, between, positions, -, 194, and, -, 172, of, the, alphaV, promoter, region, and, are, directly, involved, in, the, regulation, of, transcriptional, activity, of, the, alphaV, gene, in, human, umbilical, vascular, endothelial, cells, '(', 'HUVECs)', '(', 'Czyz', &, 'amp;', 'Cierniewski,', 1999, ',', 'Eur'])]). relacion([sujeto(['In', this]), verbo([report]), complemento([we, provide, evidence, that, the, 'GATA-1', factor, regulates, alphaV, expression, during, differentiation, of, pluripotent, 'K562', cells, induced, either, by, phorbol, 12, -, myristate, 13, -, acetate, '(', 'PMA)', or, butyric, acid, '(', 'BA)', through, interaction, with, the, 'GATA', element, in, the, alphaV, gene, promoter])]). relacion([sujeto(['DNase', 'I', footprinting, analysis, revealed, that, region, -, 413, to, -, 408, ',', covering, the, 'GATA']), verbo([binding]), complemento(['site,', was, protected, by, nuclear, extract, from, 'K562', cells])]). relacion([sujeto(['There', was, no, protection, of, this, region, by, 'HUVEC']), verbo([nuclear]), complemento([extract])]). relacion([sujeto(['Electrophoretic', mobility, shift, assay, '(', 'EMSA)', analysis, of]), verbo([nuclear]), complemento([extract, of, 'K562', cells, treated, with, 'BA', revealed, an, increase, in, 'GATA', binding, 'activity,', which, was, associated, with, reduced, alphaV, mRNA, and, alphaV, protein, on, the, cell, surface])]). relacion([sujeto(['Stimulation', of, 'K562', cells, with, 'PMA', resulted, in, opposite, 'effects:', lower, expression, of, 'GATA-1', was]), verbo([associated]), complemento([with, increased, levels, of, alphaV])]). relacion([sujeto(['We', conclude, that, the, 'GATA-1', transcription, factor, specifically]), verbo([binds]), complemento([to, the, 'GATA', element, in, the, alphaV, gene, promoter, and, negatively, regulates, alphaV, gene, expression])]). relacion([sujeto(['The', cells]), verbo([stimulated]), complemento([with, 'PMA', in, early, 'S', phase, showed, cell, cycle, arrest, in, 'G2', phase])]). relacion([sujeto(['In', 'addition,', the, cells]), verbo([stimulated]), complemento([with, 'PMA', in, early, 'G1', phase, showed, cell, cycle, arrest, in, late, 'G1'])]). relacion([sujeto(['The', expression, of, 'gpIIb/IIIa,', megakaryocytic, differentiation, 'marker,', was, markedly]), verbo([induced]), complemento([in, 'G2', phase, when, the, cells, were, stimulated, in, early, 'S', 'phase,', and, was, also, induced, in, late, 'G1', phase, when, cells, were, stimulated, in, early, 'G1', phase])]). relacion([sujeto(['Therefore,', the, induction, of, 'gpIIb/IIIa', expression, seems, to, be]), verbo([associated]), complemento([with, cell, cycle, blockage, in, both, 'G2', and, late, 'G1'])]). relacion([sujeto(['Expression', of, the, transcription, factor, 'GATA-1', in, cells]), verbo([stimulated]), complemento([in, early, 'S', phase, was, much, higher, than, that, in, controls, at, 'G2', phase])]). relacion([sujeto(['Furthermore,', 'GATA-1', expression, in, cells]), verbo([stimulated]), complemento([in, early, 'G1', tended, to, be, higher, than, that, in, controls, at, late, 'G1'])]). relacion([sujeto(['These', periods, corresponded, to, the, time, that, the, cell, cycle]), verbo([arrest]), complemento([and, 'gpIIb/IIIa', expression, were, induced, by, 'PMA'])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, the, cell, cycle, in, human, megakaryocytic, lineage, cells, may, have, two, regulation, points, for, differentiation])]). relacion([sujeto(['TPA']), verbo([induced]), complemento(['MC3', cells, to, differentiate, to, an, early, stage, of, megakaryocyte, lineage, exhibiting, an, increase, in, the, expression, of, platelet, glycoproteins, '(', 'GP)', 'IIb/IIIa', '(', 'CD41a),', and, an, increase, in, cell, size, and, nuclear, ploidy])]). relacion([sujeto(['TPA', treatment, also]), verbo([enhanced]), complemento([the, expression, of, 'GPIIb', 'mRNA,', and, induced, the, expression, of, 'interleukin-6', '(', 'IL-6)', and, its, receptor, 'mRNAs,', while, it, did, not, induce, transcripts, of, the, genes, 'IL-11', and, mpl, 'ligand,', and, further, decreased, the, transcript, of, the, mpl, gene])]). relacion([sujeto(['Consistent', with, these, 'findings,', 'MC3', cells, treated, with, 'TPA', showed, an]), verbo([increased]), complemento([expression, of, 'GATA-1,', but, not, 'GATA-3', 'transcripts,', whereas, those, without, 'TPA', treatment, expressed, only, the, 'GATA-2', transcript])]). relacion([sujeto(['These', results]), verbo([provide]), complemento([an, insight, into, the, study, for, the, regulatory, mechanism, of, megakaryocytopoiesis, and, leukemic, cell, differentiation])]). relacion([sujeto(['The', 'NS-Meg', cells, spontaneously, produced, 'platelet-like', particles, which, contained, 'alpha-granules,', mitochondria, and, dense, 'bodies,', strongly]), verbo([suggesting]), complemento([platelet, production])]). relacion([sujeto(['Erythropoietin', '(', 'Epo),', 'granulocyte/macrophage', colony]), verbo([stimulating]), complemento(['factor(GM-CSF),', and, interleukin, 3, '(', 'IL-3)', promoted, the, growth, of, 'NS-Meg', cells])]). relacion([sujeto(['Phorbol-12-myristate-13-acetate']), verbo([increased]), complemento([the, expression, of, both, 'CD41a', and, 'CD61', antigens])]). relacion([sujeto(['Ten-day', exposure, to, 'Epo']), verbo([induced]), complemento([mature, erythroblasts, and, red, cells])]). relacion([sujeto(['Untreated', 'NS-Meg', cells]), verbo([expressed]), complemento([mRNA, for, the, 'Epo', receptor, '(', 'EpoR),', for, 'GATA-1,', and, for, alpha, 1, ',', alpha, 2, and, gamma, globin, genes])]). relacion([sujeto(['With', erythroid, 'differentiation,', committed, progenitor, cells, acquire, the, ability, to]), verbo([respond]), complemento([to, erythropoietin, '(', 'Epo)'])]). relacion([sujeto(['Epo']), verbo([interacts]), complemento([with, target, cells, through, the, 'Epo', receptor, '(', 'Epo-R),', whose, expression, is, tightly, regulated, in, a, 'lineage-specific', fashion])]). relacion([sujeto(['Epo-R', expression, is, presumed, to, be, progressively]), verbo([activated]), complemento([or, repressed, as, cells, progress, along, the, erythroid, or, the, myeloid, 'pathway,', respectively])]). relacion([sujeto(['GATA-1,', the, major, known, transcription, factor]), verbo([involved]), complemento([in, 'Epo-R', gene, 'regulation,', is, not, 'erythroid-specific'])]). relacion([sujeto(['We']), verbo([have]), complemento([studied, the, regulation, of, the, expression, of, the, 'Epo-R', gene, in, two, related, human, 'Epo-responsive', cell, 'lines,', 'UT-7', and, 'UT-7', 'Epo'])]). relacion([sujeto(['These', lines]), verbo([express]), complemento(['Epo-R', at, high, levels, because, of, amplification, of, the, endogenous, 'gene,', which, is, apparently, not, rearranged])]). relacion([sujeto(['Treatment', for, 6, to, 24, hours, with, the, tumor, 'promoter,', phorbol, myristate, acetate, '(', 'PMA),', or, 24, hours, of, growth, factor, starvation, '(', 'Epo', or, 'granulocyte/macrophage', 'colony-stimulating', factor, '[', 'GM-CSF])']), verbo([decreased]), complemento([or, increased, the, levels, of, 'Epo-R', 'mRNA,', respectively])]). relacion([sujeto(['In', the, case, of, growth, factor, 'starvation,', the]), verbo([increase]), complemento(['(', approximately, equal, to, 'threefold)', in, the, level, of, 'Epo-R', mRNA, correlated, directly, with, an, increase, in, the, rate, of, 'Epo-R', gene, transcription, as, measured, by, 'run-off', assay])]). relacion([sujeto(['Both']), verbo([increases]), complemento([were, observed, as, early, as, 3, hours, after, the, growth, factor, was, withdrawn, and, were, 'reversible;', levels, of, mRNA, and, transcription, rates, returned, to, baseline, 3, hours, after, the, cells, were, reexposed, to, growth, factors])]). relacion([sujeto(['The', changes, in, 'Epo-R', expression, after, growth, factor, starvation, were, coordinated, with, changes, in, the, level, of, expression, of, 'GATA-1', that, were, detected, both, at, the, mRNA, and, at, the, gene, transcription, level, under, these, conditions, '(']), verbo([suggesting]), complemento([that, 'GATA-1', was, responsible, for, this, 'upregulation)'])]). relacion([sujeto(['During', 'PMA', 'treatment,', after, a, transient]), verbo([increase]), complemento([in, 'Epo-R', mRNA, at, 1, 'hour,', a, progressive, decline, in, the, level, of, 'Epo-R', mRNA, was, 'observed;', the, level, of, 'Epo-R', mRNA, decreased, by, 50, '%', ',', and, fell, below, the, level, of, detection, by, 6, and, 24, 'hours,', respectively])]). relacion([sujeto(['The', changes, in, transcription, rate, occurred, in, the, absence, of, changes, in, the, level, of, 'GATA-1']), verbo([binding]), complemento([activity])]). relacion([sujeto(['(', 'ABSTRACT', 'TRUNCATED', 'AT', 400, 'WORDS)', 'Phorbol', myristate, acetate, '(', 'PMA)']), verbo([induces]), complemento([the, expression, of, megakaryocyte, 'and/or', platelet, proteins, during, terminal, differentiation, of, human, erythroleukemia, '(', 'HEL)', cells])]). relacion([sujeto(['However,', it, is, not, established, whether, megakaryocytic, differentiation, is, accompanied, by, the, downregulation, of, the, major, erythroid, transcription, factor, 'GATA-1', and, the, concomitant]), verbo([loss]), complemento([of, the, erythrocytic, phenotype])]). relacion([sujeto(['Studies', of, the, molecular, mechanism, of, 'PMA-induced', differentiation, in, 'HEL', cells, showed, that, when, 'HEL', cells, are, treated, with, 'PMA,', they, dramatically]), verbo([decrease]), complemento([the, expression, of, the, 'erythroid-specific', gene, glycophorin, 'A', at, the, mRNA, level, but, apparently, not, at, the, 'steady-state', protein, level])]). relacion([sujeto(['The', coordinated, negative, regulation, of, glycophorin, 'A', mRNA, and, 'GATA-1', expression, after, 'PMA', treatment]), verbo([suggests]), complemento([that, downregulation, of, 'GATA-1', expression, may, be, partially, responsible, for, the, loss, of, the, erythroid, phenotype, during, megakaryocytic, differentiation])]). relacion([sujeto(['The']), verbo([reported]), complemento([data, also, suggest, that, 'GATA-1', activity, may, not, be, essential, for, obtaining, megakaryocytic, phenotype, during, terminal, differentiation, in, 'HEL', cells])]). relacion([sujeto(['Inhibition', of, differentiation]), verbo([has]), complemento([been, proposed, as, an, important, mechanism, for, 'Myc-induced', 'tumorigenesis,', but, the, mechanisms, involved, are, unclear])]). relacion([sujeto(['We']), verbo([have]), complemento([established, a, genetically, defined, differentiation, model, in, human, leukemia, 'K562', cells, by, conditional, expression, of, the, 'cyclin-dependent', kinase, '(', 'Cdk)', inhibitor, p27, '(', inducible, by, 'Zn(2+))', and, 'Myc', '(', activatable, by, 4, -, 'hydroxy-tamoxifen)'])]). relacion([sujeto(['Interestingly,', activation, of, 'Myc']), verbo([inhibited]), complemento(['p27-mediated', erythroid, differentiation, without, affecting, 'p27-mediated', proliferation, arrest])]). relacion([sujeto(['Moreover,', 'Myc', also, blocked, the, upregulation, of, 'Mad1,', a, transcriptional, antagonist, of, 'Myc', that, is, able, to]), verbo([induce]), complemento([erythroid, differentiation])]). relacion([sujeto(['Lead', '(', 'Pb)', and, cadmium, '(', 'Cd)', are, heavy, metal, toxins, that]), verbo([cause]), complemento([many, pathophysiologic, 'effects,', including, anemia])]). relacion([sujeto(['Previous', in, vitro, studies]), verbo([have]), complemento([shown, that, these, metals, are, able, to, replace, coordinated, 'Zinc', '(', 'Zn)', atoms, in, the, 'Zn', fingers, of, transcription, factors, and, that, this, can, alter, the, structure, and, 'DNA-binding', characteristics, of, these, proteins])]). relacion([sujeto(['This']), verbo([has]), complemento([lead, to, the, hypothesis, that, one, mechanism, underlying, the, toxic, effects, of, 'Pb', and, 'Cd', is, their, ability, to, alter, 'Zn', finger, transcription, factor, function, resulting, in, aberrant, target, gene, expression])]). relacion([sujeto(['A', recent]), verbo([report]), complemento([that, 'Pb', is, able, to, replace, 'Zn', in, the, 'Zn', fingers, of, the, hematopoietic, transcription, factor, 'GATA-1', prompted, us, to, address, this, hypothesis, in, the, setting, of, 'MEL', cell, differentiation])]). relacion([sujeto(['If', 'Pb', or, 'Cd', is, able, to]), verbo([inhibit]), complemento(['GATA-1', 'function,', this, should, be, detectable, through, alterations, in, chemically, induced, erythroid, differentiation, and, 'GATA-1-dependent', gene, expression])]). relacion([sujeto(['Despite', a, strong, rationale, for, this, 'hypothesis,', we]), verbo([have]), complemento([found, no, significant, change, in, 'MEL', 'differentiation,', the, expression, of, several, 'GATA-1', target, 'genes,', or, of, in, vitro, and, in, vivo, 'GATA-1', binding, to, 'DNA', at, concentrations, well, above, those, associated, with, toxic, effects, in, humans])]). relacion([sujeto(['EVI1', is, an, aggressive]), verbo([nuclear]), complemento([oncoprotein, deregulated, by, recurring, chromosomal, abnormalities, in, myelodysplastic, syndrome, '(', 'MDS)'])]). relacion([sujeto(['The', expression, of, the, corresponding, gene, is, a, very, poor, prognostic, marker, for, 'MDS', patients, and, is]), verbo([associated]), complemento([with, severe, defects, of, the, erythroid, lineage])]). relacion([sujeto(['We']), verbo([have]), complemento([recently, shown, that, the, constitutive, expression, of, 'EVI1', in, murine, bone, marrow, results, in, a, fatal, disease, with, features, characteristic, of, 'MDS,', including, 'anemia,', 'dyserythropoiesis,', and, dysmegakaryopoiesis])]). relacion([sujeto(['These', lineages, are]), verbo([regulated]), complemento([by, the, 'DNA-binding', transcription, factor, 'GATA1'])]). relacion([sujeto(['EVI1']), verbo([has]), complemento([two, zinc, finger, domains, containing, seven, motifs, at, the, 'N', terminus, and, three, motifs, at, the, 'C', terminus])]). relacion([sujeto(['Here,', 'however,', we, show, that, 'EVI1', is, unable, to]), verbo([bind]), complemento([to, classic, 'GATA1', sites])]). relacion([sujeto(['The', results, indicate, that, 'EVI1']), verbo([interacts]), complemento([directly, with, the, 'GATA1', protein, rather, than, the, 'DNA', sequence])]). relacion([sujeto(['We', further, show, that, this, 'protein-protein', interaction, blocks, efficient, recognition, or]), verbo([binding]), complemento([to, 'DNA', by, 'GATA1'])]). relacion([sujeto(['Point', mutations, that, disrupt, the, geometry, of, two, zinc, fingers, of, 'EVI1', abolish, the, 'protein-protein', 'interaction,']), verbo([leading]), complemento([to, normal, erythroid, differentiation, of, normal, murine, bone, marrow, in, vitro])]). relacion([sujeto(['The', 'Dof', '(', 'DNA-binding', with, one, 'finger)', proteins, are, plant, transcription, factors, that]), verbo([have]), complemento([a, highly, conserved, 'DNA-binding', 'domain,', called, the, 'Dof', domain])]). relacion([sujeto(['The', 'Dof', 'domain,', which, is, composed, of, 52, amino, acid, 'residues,', is, similar, to, the, 'Cys2/Cys2', zinc, finger, 'DNA-binding', domain, of, 'GATA1', and, steroid, hormone, 'receptors,', but]), verbo([has]), complemento([a, longer, putative, loop, than, that, in, the, case, of, these, zinc, finger, domains])]). relacion([sujeto(['The', 'DNA-binding', function, of, ascorbate, oxidase, gene]), verbo([binding]), complemento([protein, '(', 'AOBP),', a, 'Dof', 'protein,', was, investigated, by, gel, retardation, analysis])]). relacion([sujeto(['Furthermore,', heavy, metals, such, as, 'Co(II),', 'Ni(II),', 'Cd(II),', 'Cu(II),', 'Hg(II),', 'Fe(II),', and, 'Fe(III)']), verbo([inhibited]), complemento([the, 'DNA-binding', activity, of, the, 'Dof', domain])]). relacion([sujeto(['Agents', that]), verbo([target]), complemento([the, two, highly, conserved, 'Zn', fingers, of, the, human, immunodeficiency, virus, '(', 'HIV)', nucleocapsid, p7, '(', 'NCp7)', protein, are, under, development, as, antivirals])]). relacion([sujeto(['These', agents, covalently, modify, 'Zn-coordinating', cysteine, thiolates, of, the, 'fingers,']), verbo([causing]), complemento(['Zn', 'ejection,', loss, of, native, protein, structure, and, nucleic, acid, binding, 'capacity,', and, disruption, of, virus, replication])]). relacion([sujeto(['Concentrations', of, three, antiviral, agents, that]), verbo([promoted]), complemento([in, vitro, 'Zn', ejection, from, 'NCp7', and, inhibited, 'HIV', replication, did, not, impact, the, functions, of, cellular, 'Zn', finger, 'proteins,', including, 'poly(ADP-ribose)', polymerase, and, the, 'Sp1', and, 'GATA-1', transcription, 'factors,', nor, did, the, compounds, inhibit, 'HeLa', nuclear, extract, mediated, transcription])]). relacion([sujeto(['Further', modeling, analysis]), verbo([suggests]), complemento([that, the, thiolate, of, 'Cys49', in, the, 'carboxy-terminal', finger, is, the, site, most, susceptible, to, electrophilic, attack])]). relacion([sujeto(['These', data]), verbo([provide]), complemento([the, first, experimental, evidence, and, rationale, for, antiviral, agents, that, selectively, target, retroviral, nucleocapsid, protein, 'Zn', fingers])]). relacion([sujeto(['Here,', we, demonstrate, that, 'GATA1', monovalently]), verbo([binds]), complemento([to, a, single, 'GATA', motif, '(', 'Single-GATA)', while, a, monomeric, 'GATA1', and, a, homodimeric, 'GATA1', bivalently, bind, to, two, 'GATA', motifs, in, palindromic, '(', 'Pal-GATA)', and, 'direct-repeat', '(', 'Tandem-GATA)', 'arrangements,', 'respectively,', and, form, higher, stoichiometric, complexes, on, respective, elements])]). relacion([sujeto(['GATA1', lacking, the, 'N', 'finger-DNA', association, fails, to]), verbo([trigger]), complemento([a, rate, of, target, gene, expression, comparable, to, that, seen, with, the, 'wild-type', 'GATA1,', especially, when, expressed, at, low, level])]). relacion([sujeto(['This', study, revealed, that, 'Pal-GATA', and, 'Tandem-GATA', generate, transcriptional, responses, from, 'GATA1']), verbo([target]), complemento([genes, distinct, from, the, response, of, 'Single-GATA'])]). relacion([sujeto(['Our', results, support, the, notion, that, the, distinct, alignments, in]), verbo([binding]), complemento([motifs, are, part, of, a, critical, regulatory, strategy, that, diversifies, and, modulates, transcriptional, regulation, by, 'GATA1'])]). relacion([sujeto(['Congenital', erythropoietic, porphyria, '(', 'CEP)', is, characterized, in, most, individuals, by, severe, cutaneous, photosensitivity, with, blistering, and]), verbo([increased]), complemento([friability, of, the, skin, over, 'light-exposed', areas])]). relacion([sujeto(['Hemolytic', anemia, is, common, and, can, range, from, mild, to, 'severe,', with, some, affected, individuals]), verbo([requiring]), complemento([chronic, blood, transfusions])]). relacion([sujeto(['Porphyrin', deposition, may]), verbo([lead]), complemento([to, corneal, ulcers, and, 'scarring,', 'reddish-brown', discoloration, of, the, teeth, '(', 'erythrodontia),', and, mild, bone, loss, 'and/or', expansion, of, the, bone, marrow])]). relacion([sujeto(['The', diagnosis, of, 'CEP', is, supported, by, the, biochemical, findings, of, markedly]), verbo([decreased]), complemento([uroporphyrinogen, '(', 'URO)-synthase', activity, in, erythrocytes, 'and/or', markedly, increased, levels, of, urinary, uroporphyrin, 'I', and, coproporphyrin, 'I', isomers])]). relacion([sujeto(['Wound', care, is, necessary, to]), verbo([prevent]), complemento([infection, of, opened, 'blisters;', surgical, intervention, may, be, 'necessary;', blood, transfusions, are, necessary, when, hemolysis, is, significant])]). relacion([sujeto(['In', those, with, hepatic, 'dysfunction:', avoid, drugs, that, may]), verbo([induce]), complemento([cholestasis])]). relacion([sujeto(['Pregnancy', 'management:', 'Protective', filters, for, artificial, lights, should, be, used, in, the, 'delivery/operating', room, to]), verbo([prevent]), complemento([phototoxic, damage, to, the, mother, during, delivery])]). relacion([sujeto(['Other:', 'Neither', 'beta-carotene', nor, phototherapy, with, 'narrow-band', ultraviolet, 'B', radiation]), verbo([has]), complemento([been, beneficial])]). relacion([sujeto(['CEP']), verbo([caused]), complemento([by, biallelic, 'UROS', pathogenic, variants, is, inherited, in, an, autosomal, recessive, '(', 'AR)', manner])]). relacion([sujeto(['CEP']), verbo([caused]), complemento([by, a, 'GATA1', pathogenic, variant, is, inherited, in, an, 'X-linked', '(', 'XL)', manner])]). relacion([sujeto(['At', 'conception,', each, sib, of, an, affected, individual]), verbo([has]), complemento([a, 25, '%', chance, of, being, 'affected,', a, 50, '%', chance, of, being, an, asymptomatic, 'carrier,', and, a, 25, '%', chance, of, being, unaffected, and, not, a, carrier])]). relacion([sujeto(['Carrier', testing, for, 'at-risk', family, members, and, prenatal, testing, for, pregnancies, at]), verbo([increased]), complemento([risk, are, possible, if, the, pathogenic, variants, in, the, family, have, been, identified])]). relacion([sujeto(['Males', who, inherit, the, pathogenic, variant, will, be, 'affected;', females, who, inherit, the, pathogenic, variant, will, be, heterozygotes, and, can, be, either, asymptomatic, or]), verbo([have]), complemento([a, milder, phenotype])]). relacion([sujeto(['The', polarity, protein, 'Scrib', is, highly]), verbo([expressed]), complemento([in, endothelial, cells, and, is, required, for, planar, cell, polarity])]). relacion([sujeto(['Cytokine', treatment, of, human, umbilical, vein, endothelial, cells]), verbo([induced]), complemento([an, inflammatory, response, as, evident, by, the, induction, of, vascular, cell, adhesion, 'molecule-1', '(', 'VCAM-1)'])]). relacion([sujeto(['This', effect, was, specific, for, 'Scrib', and, not]), verbo([mediated]), complemento([by, other, polarity, proteins])]). relacion([sujeto(['Moreover,', it, did, not]), verbo([involve]), complemento([integrin, α5, or, classic, pathways, supporting, inflammatory, 'signaling,', such, as, nuclear, factor, κ, light, chain, enhancer, of, activated, 'B-cells', or, 'MAP', kinases])]). relacion([sujeto(['Co-immunoprecipitation/mass', spectrometry, identified, the, zinc, finger, transcription, factor, 'GATA-like', 'protein-1', as, a, novel, 'Scrib']), verbo([interacting]), complemento([protein])]). relacion([sujeto(['Small', interfering, 'RNA', depletion, of, 'GATA-like', 'protein-1']), verbo([decreased]), complemento([the, tumor, necrosis, 'factor-α-stimulated', 'VCAM-1', induction, to, a, similar, extent, as, loss, of, 'Scrib', did])]). relacion([sujeto(['Scrib', is, a, novel, proinflammatory, regulator, in, endothelial, 'cells,', which]), verbo([maintains]), complemento([the, protein, expression, of, 'GATA-like', 'protein-1'])]). relacion([sujeto(['Eukaryotic', gene, expression, is, developmentally, 'regulated,', in, part, by, chromatin, 'remodelling,', and, its, dysregulation]), verbo([has]), complemento([been, linked, to, cancer])]). relacion([sujeto(['CHD5', encodes, a, protein, with, chromatin, 'remodelling,', helicase, and, 'DNA-binding', motifs, that, is, preferentially]), verbo([expressed]), complemento([in, neural, and, testicular, tissues])]). relacion([sujeto(['To', determine, if, 'CHD5', forms, a, similar, 'complex,', we, performed, studies, on]), verbo([nuclear]), complemento([extracts, from, 'NBLS,', 'SY5Y', '(', both, with, endogenous, 'CHD5', 'expression),', 'NLF', '(', 'CHD5', 'null)', and, 'NLF', cells, stably, transfected, with, 'CHD5', cDNA, '(', 'wild-type', and, 'V5-histidine-tagged)'])]). relacion([sujeto(['CHD5', was, clearly]), verbo([associated]), complemento([with, all, canonical, 'NuRD', 'components,', including, 'metastasis-associated', protein, '(', 'MTA)1/2,', 'GATA', zinc, finger, domain, containing, 2, 'A', '(', 'GATAD2A),', histone, deacetylase, '(', 'HDAC)1/2,', 'retinoblastoma-binding', protein, '(', 'RBBP)4/7', and, methyl, 'DNA-binding', domain, protein, '(', 'MBD)2/3,', as, determined, by, 'Western', blotting, and, 'MS/MS'])]). relacion([sujeto(['Our', data]), verbo([suggest]), complemento(['CHD5', forms, a, 'NuRD', complex, similar, to, 'CHD4'])]). relacion([sujeto(['However,', 'CHD5-NuRD', may, also]), verbo([have]), complemento([unique, protein, associations, that, confer, functional, specificity, and, may, contribute, to, normal, development, and, to, tumour, suppression, in, 'NB', and, other, cancers])]). relacion([sujeto(['GATA1']), verbo([interacts]), complemento([with, the, 'TP53', tumor, suppressor, 'gene,', and, both, 'GATAs', have, been, shown, to, be, involved, in, cell, 'growth,', 'apoptosis,', and, tumorigenesis, of, several, solid, tumors])]). relacion([sujeto(['GATA1', and, 'GATA2', expression, alterations, are]), verbo([associated]), complemento([with, poor, survival, and, adverse, clinicopathology, in, prostate, and, colorectal, 'cancer,', while, the, significance, and, prognostic, value, in, clear, cell, renal, cell, carcinoma, '(', 'ccRCC)', has, not, been, investigated, as, yet])]). relacion([sujeto(['GATA1', and, 'GATA2', expression, levels, were, significantly]), verbo([decreased]), complemento([in, tumor, tissues, compared, with, normal, tissues, '(', p, &, 'lt;', 0.001, ',', paired, t, 'test)'])]). relacion([sujeto(['In', univariate, logistic, regression, 'analysis,']), verbo([decreased]), complemento(['GATA1', and, 'GATA2', expression, levels, were, associated, with, advanced, tumor, disease, '(', p, =, 0.005, and, 0.008, ')', ',', positive, distant, metastasis, '(', p, =, 0.03, and, 0.001, ')', ',', and, lymph, node, metastasis, status, '(', p, =, 0.011, and, 0.038, ')'])]). relacion([sujeto(['Reduced', expression, levels, of, 'GATA1', and, 'GATA2', were]), verbo([associated]), complemento([with, an, increased, risk, of, disease, recurrence, '(', p, =, 0.005, and, 0.006, ;, hazard, ratio, =, 0.05, and, 0.21, ')'])]). relacion([sujeto(['Our', results, support, that, 'GATA1', and, 'GATA2', are]), verbo([involved]), complemento([in, ccRCC, tumor, biology, possibly, affecting, tumor, development, and, aggressiveness])]). relacion([sujeto(['The']), verbo([binding]), complemento([of, 'chromatin-associated', proteins, and, incorporation, of, histone, variants, correlates, with, alterations, in, gene, expression])]). relacion([sujeto(['These', changes]), verbo([have]), complemento([been, particularly, well, analyzed, at, the, mammalian, 'β-globin', 'locus,', where, transcription, factors, such, as, erythroid, 'Krüppel-like', factor, '(', 'EKLF),', which, is, also, known, as, 'Krüppel-like', factor, 1, '(', 'KLF1),', play, a, coordinating, role, in, establishing, the, proper, chromatin, structure, and, inducing, 'high-level', expression, of, adult, 'β-globin'])]). relacion([sujeto(['We', had, previously, shown, that, 'EKLF', preferentially]), verbo([interacts]), complemento([with, histone, 'H3', and, that, the, 'H3'])]). relacion([sujeto([3, variant, is, differentially]), verbo([recruited]), complemento([to, the, 'β-globin', promoter])]). relacion([sujeto(['We', now]), verbo([find]), complemento([that, a, novel, interaction, between, 'EKLF', and, the, histone, cell, cycle, regulation, defective, homolog, 'A', '(', 'HIRA)', histone, chaperone, accounts, for, these, effects])]). relacion([sujeto(['HIRA', is, not, only, critical, for, 'β-globin', expression, but, is, also]), verbo([required]), complemento([for, activation, of, the, erythropoietic, regulators, 'EKLF', and, 'GATA', binding, protein, 1, '(', 'GATA1)'])]). relacion([sujeto(['Our', results]), verbo([provide]), complemento([a, mechanism, by, which, transcription, 'factor-directed', recruitment, of, a, generally, expressed, histone, chaperone, can, lead, to, 'tissue-restricted', changes, in, chromatin, 'components,', 'structure,', and, transcription, at, specific, genomic, sites, during, differentiation])]). relacion([sujeto(['FOG1', is, a, transcriptional, regulator, that]), verbo([acts]), complemento([in, concert, with, the, hematopoietic, master, regulator, 'GATA1', to, coordinate, the, differentiation, of, platelets, and, erythrocytes])]). relacion([sujeto(['Despite', considerable, 'effort,', 'however,', the, mechanisms, through, which, 'FOG1']), verbo([regulates]), complemento([gene, expression, are, only, partially, understood])]). relacion([sujeto(['Here', we]), verbo([report]), complemento([the, discovery, of, a, previously, unrecognized, domain, in, 'FOG1:', a, 'PR', '(', 'PRD-BF1', and, 'RIZ)', domain, that, is, distantly, related, in, sequence, to, the, 'SET', domains, that, are, found, in, many, histone, methyltransferases])]). relacion([sujeto(['We']), verbo([have]), complemento([used, 'NMR', spectroscopy, to, determine, the, solution, structure, of, this, 'domain,', revealing, that, the, domain, shares, close, structural, similarity, with, 'SET', domains])]). relacion([sujeto(['However,', neither, pulldowns, from, mammalian]), verbo([nuclear]), complemento([extracts, nor, yeast, 'two-hybrid', assays, reproducibly, revealed, binding, 'partners,', and, we, were, unable, to, detect, 'nucleic-acid-binding', activity, in, this, domain, using, our, 'high-diversity', 'Pentaprobe', oligonucleotides])]). relacion([sujeto(['GATA', are, a, family, of, transcription, factors, characterized, by, their, ability, to]), verbo([bind]), complemento([to, the, 'DNA', sequence, &, 'quot;GATA",', and, involved, in, a, myriad, of, cellular, processes])]). relacion([sujeto(['GATA1/2/3', factors, are, known, as, the, hematopoietic, 'GATA', 'factors,', which, play, dominated, roles, in]), verbo([regulating]), complemento([hematopoiesis])]). relacion([sujeto(['The', 'full-length', cDNA, of, 'CfGATA', is, of, 2058, bp, encoding, a, predicted, polypeptide, of, 457, amino, acids, with, two]), verbo([conserved]), complemento([zinc, finger, 'domains,', which, shared, high, similarity, with, other, reported, 'GATA1/2/3', proteins])]). relacion([sujeto(['The', mRNA, transcripts, of, 'CfGATA', showed, higher, expression, in, 'gills,', 'hepatopancreas,', hemocytes, and, 'heart,', and, the, 'CfGATA', protein]), verbo([expressed]), complemento([in, 'HEK293', cells, was, found, to, be, localized, specifically, in, the, nuclei])]). relacion([sujeto(['The', recombinant, 'CfGATA', protein, '(', 'rCfGATA)', exhibited, strong, ability, to]), verbo([bind]), complemento([specific, 'WGATAR', 'DNA', sequence, by, electrophoretic, mobility, shift, assay, in, vitro])]). relacion([sujeto(['After', 'CfGATA', gene, was, silenced, by, 'RNA', 'interference,', the, hemocyte, renewal, rate, and, circulating, total, hemocyte, count, '(', 'THC)']), verbo([decreased]), complemento(['significantly,', which, was, 7.85, -, fold, and, 19.46, -, fold, lower, than, that, of, 'PBS', 'control,', respectively, '(', 'P', &, 'lt;', 0.05, ')'])]). relacion([sujeto(['After', 'LPS', 'stimulation,', the, expression, level, of, 'CfGATA', mRNA]), verbo([decreased]), complemento([significantly, in, the, hemocytes, of, 'PBS', or, 'EGFP', dsRNA, treated, 'scallops,', which, was, accompanied, by, the, increase, of, hemocyte, renewal, rate, and, the, reduced, circulating, 'THC', at, 24, h])]). relacion([sujeto(['These', results]), verbo([suggested]), complemento([that, 'CfGATA,', as, a, conserved, 'GATA1/2/3', transcription, 'factor,', plays, essential, roles, in, regulating, hemocyte, production, of, scallop])]). relacion([sujeto(['Promyelocytic', leukemia, protein, '(', 'PML)']), verbo([has]), complemento([been, implicated, as, a, participant, in, multiple, cellular, processes, including, 'senescence,', 'apoptosis,', 'proliferation,', and, differentiation])]). relacion([sujeto(['Studies', of, 'PML', function, in, hematopoietic, differentiation, previously, focused, principally, on, its, myeloid, activities, and, also, indicated, that, 'PML', is]), verbo([involved]), complemento([in, erythroid, colony, formation])]). relacion([sujeto(['In', this, 'report,', we]), verbo([found]), complemento([that, 'PML4,', a, specific, 'PML', isoform, expressed, in, erythroid, 'cells,', promotes, endogenous, erythroid, genes, expression, in, 'K562', and, primary, human, erythroid, cells])]). relacion([sujeto(['We', show, that, the, 'PML4', effect, is, 'GATA']), verbo([binding]), complemento([protein, 1, '(', 'GATA-1)', dependent, using, 'GATA-1', 'knockout/rescued', 'G1E/G1E-ER4', cells])]). relacion([sujeto(['PML4,', but, not, other, detected, 'PML', 'isoforms,', directly]), verbo([interacts]), complemento([with, 'GATA-1', and, can, recruit, it, into, 'PML', nuclear, bodies])]). relacion([sujeto(['Finally,', we, present, evidence, that, 'PML4']), verbo([enhances]), complemento(['GATA-1', occupancy, within, the, globin, gene, cluster, and, stimulates, cooperation, between, 'GATA-1', and, its, coactivator, p300])]). relacion([sujeto(['These', results, demonstrate, that, 'PML4', is, an, important, regulator, of, 'GATA-1', and]), verbo([participates]), complemento([in, erythroid, differention, by, enhancing, 'GATA-1', 'trans-activation', activity])]). relacion([sujeto(['The', 'MED1', subunit, of, the, 'Mediator', transcriptional, coregulator, complex, coactivates, 'GATA1', and]), verbo([induces]), complemento([erythropoiesis])]). relacion([sujeto(['An', 'N-terminal', fragment, of, 'MED1,', 'MED1(1-602),', which, is, incapable, of]), verbo([interacting]), complemento([with, 'GATA1,', enhanced, 'GATA1-targeted', gene, transcription, and, erythroid, 'differentiation,', and, introduction, of, 'MED1(1-602)', into, 'Med1(-/-)', mouse, embryonic, fibroblasts, '(', 'MEFs)', partially, rescued, 'GATA1-mediated', transcription])]). relacion([sujeto(['The', 'C-terminal', 'zinc-finger', domain, of, 'GATA1']), verbo([interacts]), complemento([with, the, 'MED1(1-602)-interacting', coactivator, 'CCAR1,', 'CoCoA', and, 'MED1(681-715)'])]). relacion([sujeto(['CCAR1', and, 'CoCoA', synergistically]), verbo([enhanced]), complemento(['GATA1-mediated', transcription, from, the, 'γ-globin', promoter, in, 'MEFs'])]). relacion([sujeto(['Recombinant', 'GATA1,', 'CCAR1,', 'CoCoA', and, 'MED1(1-602)', formed, a, complex, in, 'vitro,', and, 'GATA1,', 'CCAR1,', 'CoCoA', and, 'MED1', were]), verbo([recruited]), complemento([to, the, 'γ-globin', promoter, in, 'K562', cells, during, erythroid, differentiation])]). relacion([sujeto(['Hematopoiesis', is]), verbo([regulated]), complemento([by, transcription, factors, that, induce, cell, fate, and, differentiation, in, hematopoietic, stem, cells, into, fully, differentiated, hematopoietic, cell, types])]). relacion([sujeto(['The', transcription, factor, zinc, finger, protein, 148, '(', 'Zfp148)']), verbo([interacts]), complemento([with, the, hematopoietic, transcription, factor, 'Gata1', and, has, been, implicated, to, play, an, important, role, in, primitive, and, definitive, hematopoiesis, in, zebra, fish, and, mouse, chimeras])]). relacion([sujeto(['We']), verbo([have]), complemento([recently, created, a, 'gene-trap', knockout, mouse, model, deficient, for, 'Zfp148,', opening, up, for, analyses, of, hematopoiesis, in, a, conventional, 'loss-of-function', model, in, vivo])]). relacion([sujeto(['Here,', we, show, that, 'Zfp148-deficient', neonatal, and, adult, mice]), verbo([have]), complemento([normal, or, slightly, increased, levels, of, 'hemoglobin,', 'hematocrit,', platelets, and, white, blood, 'cells,', compared, to, wild, type, controls])]). relacion([sujeto(['Despite', many, attempts, to]), verbo([find]), complemento([the, in, vivo, role, of, the, 'protein,', the, molecular, function, is, still, largely, unknown])]). relacion([sujeto(['Sertoli', cells, in, testes, lacking, 'Tzfp', display, an]), verbo([increase]), complemento([in, 'Androgen', 'Receptor', '(', 'AR)', 'signaling,', and, several, genes, in, the, 'testis,', including, 'Gata1,', 'Aie1', and, 'Fanc,', show, increased, expression])]). relacion([sujeto(['Our', results, indicate, that, 'Tzfp', function, as, a, transcriptional, regulator, and, that]), verbo([loss]), complemento([of, the, protein, leads, to, alterations, in, 'AR', signaling, and, reduced, number, of, apoptotic, cells, in, the, testicular, tubules])]). relacion([sujeto(['In', concert, with, the, transacting, factor, 'GATA1,', 'KLF1']), verbo([modulates]), complemento([the, coordinate, expression, of, the, genes, encoding, the, 'multi-enzyme', heme, biosynthetic, pathway, during, erythroid, differentiation])]). relacion([sujeto(['To', explore, the, mechanisms, underpinning, 'KLF1', action, at, the, gene, loci]), verbo([regulating]), complemento([the, first, 3, steps, in, this, 'process,', we, have, exploited, the, 'K1-ERp', erythroid, cell, 'line,', in, which, 'KLF1', translocates, rapidly, to, the, nucleus, in, response, to, treatment, with, 4, -, 'OH-Tamoxifen', '(', 4, -, 'OHT)'])]). relacion([sujeto(['KLF1']), verbo([acts]), complemento([as, a, 'differentiation-independent', transcriptional, 'co-regulator', of, 'delta-aminolevulinic', acid, dehydratase, '(', 'Alad),', but, not, 5, -, aminolevulinate, synthase, gene, '(', 'Alas2)', or, porphobilinogen, deaminase, '(', 'Pbgd)'])]). relacion([sujeto(['Similar', to, its, role, at, the, 'β-globin', 'promoter,', 'KLF1']), verbo([induces]), complemento([factor, recruitment, and, chromatin, changes, at, the, 'Alad1b', promoter, in, a, 'temporally-specific', manner])]). relacion([sujeto(['Furthermore,', 'KLF1-dependent', events, were, not]), verbo([modulated]), complemento([by, 'GATA1', factor, promoter, 'co-occupancy', alone])]). relacion([sujeto(['These', results, not, only]), verbo([enhance]), complemento([our, understanding, of, 'erythroid-specific', modulation, of, heme, biosynthetic, regulation, by, 'KLF1,', but, provide, a, model, that, will, facilitate, the, elucidation, of, novel, 'KLF1-dependent', events, at, erythroid, gene, loci, that, are, independent, of, 'GATA1', activity])]). relacion([sujeto(['The', depletion, of, kzp]), verbo([led]), complemento([to, defects, in, primitive, hematopoiesis, including, the, development, of, the, erythroid, and, myeloid, lineages])]). relacion([sujeto(['On', the, other, 'hand,', overexpression, of, kzp]), verbo([caused]), complemento([the, ectopic, expression, of, 'gata1,', 'gata2,', and, pu])]). relacion([sujeto(['Chromosome', immunoprecipitation, assays, revealed, that, 'Kzp', protein, directly]), verbo([binds]), complemento([to, 'gata1,', 'gata2,', and, pu])]). relacion([sujeto([1, to]), verbo([modulate]), complemento([primitive, hematopoiesis])]). relacion([sujeto(['The', zinc, finger, transcription, factors, 'GATA1', and, 'GATA2']), verbo([participate]), complemento([in, mast, cell, development])]). relacion([sujeto(['Although', the, expression, of, these, factors, is]), verbo([regulated]), complemento([in, a, cell, 'lineage-specific', and, differentiation, 'stage-specific', 'manner,', their, regulation, during, mast, cell, development, has, not, been, clarified])]). relacion([sujeto(['Here,', we, show, that, the, 'GATA2', mRNA, level, was, significantly]), verbo([increased]), complemento([while, 'GATA1', was, maintained, at, low, levels, during, the, differentiation, of, mast, cells, derived, from, mouse, bone, marrow, '(', 'BMMCs)'])]). relacion([sujeto(['Chromatin', immunoprecipitation, assays, revealed, that, both, 'GATA', factors]), verbo([bound]), complemento([to, most, of, the, conserved, 'GATA', sites, of, 'Gata1', and, 'Gata2', loci, in, 'BMMCs'])]). relacion([sujeto(['However,', the, 'GATA1', hematopoietic, enhancer, '(', 'G1HE)', of, the, 'Gata1', 'gene,', which, is, essential, for, 'GATA1', expression, in, erythroid, and, megakaryocytic, 'lineages,', was]), verbo([bound]), complemento([only, weakly, by, both, 'GATA', factors, in, 'BMMCs'])]). relacion([sujeto(['Collectively,', these, results, demonstrate, that, the, expression, of, 'GATA', factors, in, mast, cells, is]), verbo([regulated]), complemento([in, a, manner, quite, distinct, from, that, in, erythroid, cells])]). relacion([sujeto(['Recently,', 'GF1', was]), verbo([reported]), complemento([to, have, beneficial, effects, on, skin])]). relacion([sujeto(['However,', there]), verbo([has]), complemento([not, been, a, sound, understanding, of, its, antimelanogenic, effect, and, underlying, molecular, mechanisms])]). relacion([sujeto(['However,', it, did, not]), verbo([suppress]), complemento([intracellular, melanin, 'levels,', tyrosinase, activity, and, expression])]). relacion([sujeto(['Immunofluorescence', assay, showed, that, 'GF1', had, no, effect, on, melanosome, 'transport,', but, significantly]), verbo([induced]), complemento([dendrite, retraction])]). relacion([sujeto(['Pull-down', assay, demonstrated, that, 'GF1', primarily]), verbo([modulates]), complemento([the, 'Rho', family, 'GTPases', resulting, in, dendrite, retraction])]). relacion([sujeto(['Collectively,', these, data]), verbo([suggest]), complemento([that, 'GF1', could, act, as, a, potent, 'skin-whitening', agent])]). relacion([sujeto(['A', dysregulation, of, 'TRPC6', activity]), verbo([causes]), complemento([abnormal, proliferation, of, smooth, muscle, cells, and, glomerulosclerosis])]). relacion([sujeto(['We', showed, that]), verbo([inhibiting]), complemento(['PKC', with, 'GF1', or, activating, it, with, phorbol, 12, -, myristate, 13, -, acetate, potentiated, and, inhibited, 'agonist-induced', 'Ca(2+)', 'entry,', 'respectively,', into, cells, expressing, 'TRPC6'])]). relacion([sujeto(['Similar', results, were, obtained, when, 'TRPC6', was, directly]), verbo([activated]), complemento([with, 1, -, 'oleyl-2-acetyl-sn-glycerol'])]). relacion([sujeto(['Activation', of, the, cells, with, carbachol]), verbo([increased]), complemento([the, phosphorylation, of, 'TRPC6,', an, effect, that, was, prevented, by, the, inhibition, of, 'PKC'])]). relacion([sujeto(['The']), verbo([target]), complemento([residue, of, 'PKC', was, identified, by, an, alanine, screen, of, all, canonical, 'PKC', sites, on, 'TRPC6'])]). relacion([sujeto(['Unexpectedly,', all, the, 'mutants,', including, 'TRPC6(S768A)', '(', a, residue, previously, proposed, to, be, a]), verbo([target]), complemento([for, 'PKC),', displayed, 'PKC-dependent', inhibition, of, channel, activity])]). relacion([sujeto(['Phosphorylation', prediction, software]), verbo([suggested]), complemento([that, 'Ser(448),', in, a, 'non-canonical', 'PKC', consensus, 'sequence,', was, a, potential, target, for, 'PKCδ'])]). relacion([sujeto(['Moreover,', activation, of, 'PKC', did, not]), verbo([enhance]), complemento([the, phosphorylation, state, of, 'TRPC6(S448A)'])]). relacion([sujeto(['Using', 'A7r5', vascular, smooth, muscle, 'cells,', which, endogenously]), verbo([express]), complemento(['TRPC6,', we, observed, that, a, novel, 'PKC', isoform, is, involved, in, the, inhibition, of, the, 'vasopressin-induced', 'Ca(2+)', entry])]). relacion([sujeto(['In', 'summary,', we]), verbo([provide]), complemento([evidence, that, 'PKCδ', exerts, a, negative, feedback, effect, on, 'TRPC6', through, the, phosphorylation, of, 'Ser(448)'])]). relacion([sujeto([23, -, 22, region]), verbo([have]), complemento([shown, instability, and, chimerism, and, are, not, a, reliable, resource, for, determining, physical, distances])]). relacion([sujeto(['A', combined, 'YAC-cosmid', contig, was, constructed, along, the, genomic, map, and, was, used, for, 'fine-mapping', of, 15, polymorphic, microsatellites, and, 30]), verbo([expressed]), complemento([sequence, tags, '(', 'ESTs)', or, sequence, transcribed, sites, '(', 'STSs),', revealing, the, following, 'order:', 'tel-(SYN-TIMP)-(DXS426-ELK1)-ZNF(CA)', 'n-L1-DXS1367-ZNF81-ZNF21-DXS6616-', '(', 'HB3-OATL1pseudogenes-DXS6950)-DXS6949-DXS694', 1, -, 'DXS7464E(MG61)-GW1E(EBP)-', 'DXS7927E(MG81)-RBM-', 'DXS722-DXS7467E(MG21)-DXS1011E-WASP-DXS6940++', +, -, 'DXS7466E(MG44)-GF1-', 'DXS226-DXS1126-DXS1240-HB1-', 'DXS7469E-(DXS6665-DXS1470)-TFE3-DXS7468E-+', +, +, 'SYP-DXS1208-HB2E-DXS573-DXS1331-', 'DXS6666-DXS1039-DXS', 1426, -, 'DXS1416-DXS7647-DXS8222-DXS6850-DXS255++', +, -, 'CIC-5-DXS146-cen'])]). relacion([sujeto(['A', 'sequence-ready', map, was, constructed, for, an, 1100, -, kb, 'gene-rich', interval, flanked, by, the, markers, 'HB3', and, 'DXS1039,', from, which, six, novel, 'ESTs/STSs', were, 'isolated,', thus]), verbo([increasing]), complemento([the, number, of, markers, used, in, this, interval, to, thirty])]). relacion([sujeto(['In', 'addition,', the, map]), verbo([provides]), complemento([the, base, to, delineate, the, corresponding, syntenic, region, in, the, 'mouse,', where, the, mutants, scurfy, and, tattered, are, localized])]). relacion([sujeto(['The', 'Gfi1', gene, encodes, a, zinc, finger, protein, which]), verbo([binds]), complemento(['DNA', and, is, involved, in, transcriptional, regulation])]). relacion([sujeto(['Identification', of, molecular, mechanisms, in, adipogenic, differentiation, pathway, might]), verbo([lead]), complemento([to, development, of, new, strategies, for, 'diagnosis,', prevention, and, therapy, of, obesity, and, associated, diseases])]). relacion([sujeto(['Cytoglobin', '(', 'Cygb),', identified, as, a, new, globin, family, member, 'protein,', is]), verbo([expressed]), complemento([in, various, tissues])]). relacion([sujeto(['Besides,', 'Cygb', overexpression, in, preadipocytes, contributed, to, the, adipogenic, differentiation, as, verified, by, detection, of, higher, lipid, droplets, and]), verbo([increased]), complemento(['PPARγ,', 'CEBPα', and, 'FABP4', expressions, with, respect, to, control, cells])]). relacion([sujeto(['The', transcription, factor, 'Bach1', may, be]), verbo([involved]), complemento([in, their, regulatory, roles, since, it, is, inactivated, by, direct, binding, of, heme])]). relacion([sujeto(['To', address, whether, 'Bach1', is]), verbo([involved]), complemento([in, the, responses, of, erythroblasts, to, iron, 'status,', low, iron, conditions, that, induced, severe, iron, deficiency, in, mice, were, established])]). relacion([sujeto(['Under', iron, 'deficiency,', extensive, gene, expression, changes, and, mitophagy, disorder, were]), verbo([induced]), complemento([during, maturation, of, erythroblasts])]). relacion([sujeto(['In', the, absence, of, 'Bach1,', the, expression, of, globin, genes, and, 'Hmox1', '(', encoding, heme, 'oxygenase-1)', was, 'de-repressed', in, erythroblasts, under, iron, 'deficiency,']), verbo([suggesting]), complemento([that, 'Bach1', represses, these, genes, in, erythroblasts, under, iron, deficiency, to, balance, the, levels, of, heme, and, globin])]). relacion([sujeto(['Moreover,', an]), verbo([increase]), complemento([in, 'genome-wide', 'DNA', methylation, was, observed, in, erythroblasts, of, 'Bach1-/-', mice, under, iron, deficiency])]). relacion([sujeto(['These', findings]), verbo([reveal]), complemento([the, principle, role, of, iron, as, a, regulator, of, gene, expression, in, erythroblast, maturation, and, suggest, that, the, 'iron-heme-Bach1', axis, is, important, for, a, proper, adaptation, of, erythroblast, to, iron, deficiency, to, avoid, toxic, aggregates, of, 'non-heme', globin])]). relacion([sujeto(['Erythroid', progenitors, that]), verbo([respond]), complemento([to, erythropoietin, '(', 'Epo)', are, present, in, the, liver, of, adult, 'Xenopus', laevis])]). relacion([sujeto(['However,', cells]), verbo([responding]), complemento([to, 'Epo', in, the, larval, liver, and, through, the, metamorphosis, period, under, hepatic, remodeling, have, not, been, characterized])]). relacion([sujeto(['Larval', 'β2-globin', was, highly]), verbo([expressed]), complemento([in, 'NF56-derived', 'cells,', while, adult, 'β2-globinwas', detected, in, those, of, 'NF66'])]). relacion([sujeto(['These', results, indicate, that, erythroid, progenitors, that]), verbo([respond]), complemento([to, 'Xenopus', laevis, 'Epo', are, maintained, in, 'pre-', and, 'post-metamorphic', 'liver,', although, the, tissue, architecture, changes, dramatically, during, metamorphosis])]). relacion([sujeto(['The', multiple, sequence, alignment, '(', 'MSA)', of, a, protein, family]), verbo([provides]), complemento([a, wealth, of, information, in, terms, of, the, conservation, pattern, of, amino, acid, residues, not, only, at, each, alignment, site, but, also, between, distant, sites])]). relacion([sujeto(['In', order, to, statistically, model, the, 'MSA', incorporating, both, 'short-range', and, 'long-range', correlations, as, well, as, 'insertions,', 'I']), verbo([have]), complemento([derived, a, lattice, gas, model, of, the, 'MSA', based, on, the, principle, of, maximum, entropy])]). relacion([sujeto(['Using', this, model, with, and, without, 'long-range', 'interactions,', 'I', analyzed, the, globin, and, 'V-set', domains, by]), verbo([increasing]), complemento([the, &, 'quot;temperature"', and, by, &, 'quot;mutating"', a, site])]). relacion([sujeto(['The', correlations, between, residue, conservation, and, various, measures, of, the, 'system\'s', stability, indicate, that, the, 'long-range', interactions, make, the, conservation, pattern, more, specific, to, the, 'structure,', and, increasingly, stabilize, better]), verbo([conserved]), complemento([residues])]). relacion([sujeto(['Tristetraprolin', '(', 'TTP)', is, implicated, in, regulation, of, 'TNF-α', 'expression;', 'however,', whether, 'TTP', is]), verbo([involved]), complemento([in, cigarette, 'smoke-induced', 'TNF-α', expression, has, not, been, determined])]). relacion([sujeto(['To', identify, the, molecular, mechanism, 'involved,', a, construct]), verbo([expressing]), complemento([the, human, 'beta-globin', reporter, mRNA, containing, the, 'TNF-α', 3, '\'', -, untranslated, region, was, generated, to, characterize, the, 'TTP', targeted, site, within, 'TNF-α', mRNA])]). relacion([sujeto(['CSE']), verbo([induced]), complemento(['TTP', 'down-regulation', in, alveolar, macrophages, and, alveolar, epithelial, cells])]). relacion([sujeto(['Reduced', 'TTP', expression, resulted, in, significantly]), verbo([increased]), complemento(['TNF-α', mRNA, stability])]). relacion([sujeto(['Importantly,']), verbo([increased]), complemento(['TNF-α', mRNA, stability, due, to, impaired, 'TTP', function, resulted, in, significantly, increased, 'TNF-α', levels, in, these, cells])]). relacion([sujeto(['Forced', 'TTP', expression, abrogated, the]), verbo([increased]), complemento(['TNF-α', mRNA, stability, and, expression, induced, by, 'CSE'])]). relacion([sujeto(['By', using, the, globin, reporter, construct, containing, 'TNF-α', mRNA, 3, '\'', -, untranslated, 'region,', the, data, indicate, that, 'TTP', directly]), verbo([targets]), complemento([the, 'adenine-', and, 'uridine-rich', region, '(', 'ARE)', of, 'TNF-α', mRNA, and, negatively, regulates, 'TNF-α', expression, at, the, 'post-transcriptional', level])]). relacion([sujeto(['The', data, demonstrate, that, cigarette, smoke, exposure, reduces, 'TTP', expression, and, impairs, 'TTP', 'function,', resulting, in, significantly]), verbo([increased]), complemento(['TNF-α', mRNA, stability, and, excessive, 'TNF-α', expression, in, alveolar, macrophages, and, epithelial, cells])]). relacion([sujeto(['The', data]), verbo([suggest]), complemento([that, 'TTP', is, a, novel, 'post-transcriptional', regulator, and, limits, excessive, 'TNF-α', expression, and, inflammatory, response, induced, by, cigarette, smoke])]). relacion([sujeto(['Allogeneic', hematopoietic, stem, cell, transplantation]), verbo([has]), complemento([been, established, for, several, decades, as, a, gene, replacement, therapy, for, patients, with, thalassemia, major, and, now, offers, very, high, rates, of, cure, to, those, who, are, able, to, access, this, therapy])]). relacion([sujeto(['Outcomes']), verbo([have]), complemento([improved, tremendously, over, the, last, decade, even, in, 'high-risk', patients])]). relacion([sujeto(['The', limited, data, available]), verbo([suggests]), complemento([that, the, 'long-term', outcome, is, also, excellent, with, &, 'gt;90%', survival, but, for, best, 'results,', hematopoietic, stem, cell, transplantation, should, be, offered, early, before, any, end, organ, damage, occurs])]). relacion([sujeto(['Inadequate', hematopoietic, stem, cell, transplantation, services, and, the, cost, of, therapy, are, other, reasons, for, the, 'same,', particularly, in, those, parts, of, the, world, which]), verbo([have]), complemento([a, high, prevalence, of, this, condition])]). relacion([sujeto(['Recently,', gene, correction, in, autologous, hematopoietic, stem, cells]), verbo([has]), complemento([been, successfully, established, using, lentiviral, 'vectors,', and, several, clinical, trials, have, been, initiated])]). relacion([sujeto(['A', gene, editing, approach, to, correct, the, β, globin, mutation, or, disrupt, 'BCL11A', to]), verbo([increase]), complemento([fetal, hemoglobin, production, has, also, been, reported, and, is, expected, to, be, introduced, in, clinical, trials, soon])]). relacion([sujeto(['Although', azanucleoside, 'DNA-hypomethylating', agents, '(', 'HMAs)', are, routinely, used, for, the, treatment, of, myelodysplastic, 'syndrome/acute', myeloid, leukaemia, '(', 'MDS/AML),', very, few, outcome, predictors]), verbo([have]), complemento([been, established])]). relacion([sujeto(['Expression', of, the, 'β-like', globin, gene, locus, is, tightly]), verbo([regulated]), complemento([by, 'DNA', 'methylation,', is, 'HMA-sensitive', 'in vitro,', and, fetal, haemoglobin, '(', 'HbF)', expression, is, under, study, as, a, potential, biomarker, for, response, of, 'MDS', patients, to, azacitidine])]). relacion([sujeto(['Pre-treatment', 'HbF', was, already, elevated, '(', &, 'gt;1·0%', of, total, 'haemoglobin)', in, 7, /, 16, and, 12, /, 36, 'patients,', and, 'HbF', was]), verbo([induced]), complemento([by, 'DAC', in, 81, '%', /, 54, '%', of, 'MDS/AML', 'patients,', respectively])]). relacion([sujeto(['Elevated', 'pre-treatment', 'HbF', was]), verbo([associated]), complemento([with, longer, median, overall, survival, '(', 'OS):', 26, '·6', vs])]). relacion([sujeto(['In', 'conclusion,', we]), verbo([provide]), complemento([first, evidence, for, 'in vivo', 'HbF', induction, by, 'DAC', in, 'MDS/AML,', and, demonstrate, prognostic, value, of, elevated, 'pre-treatment', 'HbF,', warranting, 'prospective,', randomized, studies])]). relacion([sujeto(['Thalassemia', is, an, 'inherited autosomal', recessive, blood, 'disorder,']), verbo([caused]), complemento([by, mutations, in, globin, genes, or, their, regulatory, regions])]). relacion([sujeto(['The', excess, free, 'α-globin', chains, precipitate, in, red, blood, 'cells,']), verbo([leading]), complemento([to, their, destruction, '(', 'haemolysis)', and, ineffective, erythropoiesis])]). relacion([sujeto(['The', conventional, approach, to, treatment, is, based, on, the, correction, of, haemoglobin, status, through]), verbo([regular]), complemento([blood, transfusions, and, iron, chelation, therapy, for, iron, overload])]). relacion([sujeto(['Although', conventional, treatment]), verbo([has]), complemento([the, capacity, to, improve, the, quality, of, life, of, people, with, 'ß-thalassaemia', 'major,', allogeneic, hematopoietic, stem, cell, transplantation, is, the, only, currently, available, procedure, which, has, the, curative, potential])]). relacion([sujeto(['To', evaluate, the, effectiveness, and, safety, of, different, types, of, allogeneic, hematopoietic, stem, cell, 'transplantation,', in, people, with, severe, 'transfusion-dependant', 'ß-thalassaemia', 'major,', 'ß-thalassaemia', intermedia, or, 'ß0/+-', thalassaemia, variants]), verbo([requiring]), complemento([chronic, blood, transfusion])]). relacion([sujeto(['Randomised', controlled, trials, and, 'quasi-randomised', controlled, trials, comparing, allogeneic, hematopoietic, stem, cell, transplantation, with, each, other, or, with, standard, therapy, '(']), verbo([regular]), complemento([transfusion, and, chelation, 'regimen)'])]). relacion([sujeto(['We', were, unable, to, identify, any, randomised, controlled, trials, or, 'quasi-randomised', controlled, trials, on, the, effectiveness, and, safety, of, different, types, of, allogeneic, stem, cell, transplantation, in, people, with, severe, 'transfusion-dependant', 'ß-thalassaemia', major, or, 'ß0/+-', thalassaemia, variants]), verbo([requiring]), complemento([chronic, blood, transfusion])]). relacion([sujeto(['Previous', studies]), verbo([suggest]), complemento([that, habitual, exercise, can, improve, skeletal, mitochondrial, 'function;', 'however,', to, 'date,', the, association, between, exercise, and, mitochondrial, function, in, peripheral, leukocytes, has, not, been, reported])]). relacion([sujeto(['The', aim, of, this, study, was, to, evaluate, the, relationship, between]), verbo([regular]), complemento([exercise, and, mitochondrial, function, by, measuring, leukocyte, mitochondrial, 'DNA', '(', 'mtDNA)', copy, number, in, postmenopausal, women])]). relacion([sujeto(['Stepwise', multiple, regression, analysis, showed, that]), verbo([regular]), complemento([exercise, was, independently, associated, with, mtDNA, copy, number, '(', 'β=0'])]). relacion([sujeto(['Regular', exercise, is]), verbo([associated]), complemento([with, greater, leukocyte, mtDNA, copy, number, in, postmenopausal, women])]). relacion([sujeto(['As', the, disease]), verbo([requires]), complemento(['long-term', 'care,', prevention, of, the, homozygous, state, presents, a, substantial, global, disease, burden])]). relacion([sujeto(['The', comprehensively, preventive, programs]), verbo([involve]), complemento([carrier, 'detections,', molecular, 'diagnostics,', genetic, 'counseling,', and, prenatal, diagnosis])]). relacion([sujeto(['These', are, valuable, procedures, for, couples, at, 'risk,', so, that, they, can, be, offered, options, to]), verbo([have]), complemento([healthy, offspring])]). relacion([sujeto(['The', most, critical, issue, in, any, type, of, prenatal, molecular, testing, is, maternal, cell, contamination, '(', 'MCC),', especially, when, a, fetus, is]), verbo([found]), complemento([to, inherit, a, particular, mutation, from, the, mother])]). relacion([sujeto(['Blood', was, collected, from, patients]), verbo([participating]), complemento([in, this, clinical, trial, and, nucleated, red, blood, 'cell-enriched', mononuclear, cells, were, isolated, to, facilitate, the, extraction, of, 'RNA', and, protein])]). relacion([sujeto(['RT-PCR', was, used, to, monitor, the, expression, of, globin, genes, and, p38, 'MAPK,', and, total, and]), verbo([phosphorylated]), complemento([p38, 'MAPK', expression, was, assessed, using, 'Western', blot, analysis])]). relacion([sujeto(['However,', 'Gγ-globin', mRNA, levels]), verbo([increased]), complemento([significantly, in, both, treatment, groups, '(', when, compared, with, pretreatment, 'levels)', following, 12, weeks, of, treatment])]). relacion([sujeto(['Although', neither, p38, 'MAPK', mRNA, nor, protein, levels, were, affected, by, the, 'treatments,', posttreatment, phosphorylation, of, p38, 'MAPK', was, significantly]), verbo([increased]), complemento([in, the, 'R'])]). relacion([sujeto(['These', data]), verbo([suggest]), complemento([that, the, molecular, mechanisms, that, underpin, the, efficacious, use, of, 'R'])]). relacion([sujeto(['Prenatal', diagnosis, is, the, only, effective, way, to]), verbo([prevent]), complemento([the, birth, of, a, fetus, with, severe, 'thalassemias,', which, include, hemoglobin, 'Bart\'s', hydrops, fetalis, and, thalassemia, major])]). relacion([sujeto(['To', make, a, correct, 'decision,', the, obstetrician, should]), verbo([have]), complemento([a, certain, understanding, of, the, genetics, of, thalassemias])]). relacion([sujeto(['On', the, basis, of, a, thorough, understanding, of, the, above, 'information,', clinicians, should]), verbo([have]), complemento([the, ability, to, precisely, diagnose, thalassemia, patients, and, provide, applicable, genetic, counselling, to, the, affected, families])]). relacion([sujeto(['In', 'addition,', 'NMD']), verbo([regulates]), complemento([the, expression, of, a, number, of, physiological, 'mRNAs,', for, example, transcripts, containing, long, 3, '\'', 'UTRs'])]). relacion([sujeto(['NMD-inhibition', is, not, limited, to, 'PABPC1,', but, can, also, be, achieved, by, peptides, consisting, of, the, 'PABP-interacting', motif, 2, '(', 'PAM2)', of, different, proteins, when]), verbo([recruited]), complemento([to, an, 'NMD-inhibiting', position, of, 'NMD', reporter, transcripts])]). relacion([sujeto(['The', short, 'PAM2', peptides, efficiently]), verbo([suppress]), complemento(['NMD', activated, by, a, long, 3, '\'', 'UTR,', an, 'exon-junction', complex, '(', 'EJC)', and, individual, 'EJC', 'components,', and, stabilize, a, 'PTC-containing', 'β-globin', mRNA])]). relacion([sujeto(['The', present, study, was, an, attempt, to]), verbo([reactivate]), complemento([the, 'γ-globin', gene, by, introducing, a, gene, construct, containing, 'KLF1', binding, sites, to, the, 'K562', cell, line])]). relacion([sujeto(['A', plasmid, containing, a, 192, bp, sequence, with, two, repeats, of, 'KLF1']), verbo([binding]), complemento([sites, on, 'β-globin', and, 'BCL11A', promoters, was, constructed, and, used, to, transfect, the, 'K562', cell, line])]). relacion([sujeto(['The', transfected, cells, significantly]), verbo([increased]), complemento(['γ-globin', expression, after, differentiation, compared, to, untransfected, ones])]). relacion([sujeto(['The', findings, demonstrate, that, the, spongy, effect, of, 'KLF1-binding', site, on, 'BCL11A', and, 'β-globin', promoters, can]), verbo([induce]), complemento(['γ-globin', expression, in, 'K562', cells])]). relacion([sujeto(['Polymorphisms', 'T786C', and, 'G894T', are, reportedly, affecting, eNOS, regulation, and]), verbo([have]), complemento([been, related, to, various, diseases])]). relacion([sujeto(['Moreover', 894, &, 'nbsp;TT S/S', and, 'β(0)/S', patients, tended, to]), verbo([have]), complemento([higher, hematocrit, than, 894, &, 'nbsp;GG', and, 'GT', ones])]). relacion([sujeto(['This', is, the, first]), verbo([report]), complemento([describing, the, effects, of, eNOS, polymorphisms, on, different, forms, of, 'SCD,', the, first, enrolling, 'SCD', patients, of, 'Caucasian', origin, and, the, first, determining, eNOS, mRNA, levels, in, peripheral, blood, from, 'steady-state', 'SCD', patients])]). relacion([sujeto(['Four', globins]), verbo([have]), complemento([been, identified, in, rodent, and, human, brains])]). relacion([sujeto(['Among', 'them,', 'neuroglobin,', cytoglobin, and, hemoglobin, chains, are, constitutively]), verbo([expressed]), complemento([in, normal, 'brain,', while, myoglobin, is, only, expressed, in, some, neurological, disorders])]). relacion([sujeto(['Induction', of, fetal, hemoglobin, '(', 'HbF)']), verbo([has]), complemento([therapeutic, importance, for, patients, with, 'beta-hemoglobin', disorders])]). relacion([sujeto(['Previous', studies, showed, that, 'let-7', microRNAs, '(', 'miRNAs)', are, highly]), verbo([regulated]), complemento([in, erythroid, cells, during, the, 'fetal-to-adult', developmental, 'transition,', and, that, targeting, 'let-7', mediated, the, 'up-regulation', of, 'HbF', to, greater, than, 30, '%', of, the, total, globin, levels, in, human, adult, cultured, erythroblasts])]). relacion([sujeto(['HMGA2', is, a, member, of, the, 'high-mobility', group, 'A', family, of, proteins, and, a, validated]), verbo([target]), complemento([of, the, 'let-7', family, of, miRNAs])]). relacion([sujeto(['Here', we, investigate, whether, expression, of, 'HMGA2', directly]), verbo([regulates]), complemento([fetal, hemoglobin, in, adult, erythroblasts])]). relacion([sujeto(['The', transgene, was]), verbo([regulated]), complemento([by, the, 'erythroid-specific', gene, promoter, region, of, the, human, 'SPTA1', gene, '(', 'HMGA2-OE)'])]). relacion([sujeto(['HMGA2-OE']), verbo([caused]), complemento([significant, increases, in, 'gamma-globin', mRNA, expression, and, 'HbF', to, around, 16, '%', of, the, total, hemoglobin, levels, compared, to, matched, control, transductions])]). relacion([sujeto(['Overall,', our, data]), verbo([suggest]), complemento([that, expression, of, 'HMGA2,', a, downstream, target, of, 'let-7', 'miRNAs,', causes, moderately, increased, 'gamma-globin', gene, and, protein, expression, in, adult, human, erythroblasts])]). relacion([sujeto(['It', is]), verbo([associated]), complemento([with, many, 'complications;', most, of, them, are, related, to, thrombotic, events])]). relacion([sujeto(['Three', milliliters, of, ethylenediamine, tetraacetic, acid, anticoagulated, blood, were, collected, from, each, 'subject,', 'DNA', was, extracted, by, 'salting-out', 'method,', and]), verbo([target]), complemento(['DNA', regions, of, the, 'ACE', gene, were, amplified, using, 'allele-specific', polymerase, chain, reaction])]). relacion([sujeto(['No', statistically, significant, association, was]), verbo([found]), complemento([between, 'ACE', polymorphism, and, complications, of, 'SCA'])]). relacion([sujeto(['The', structural, and, functional, conservation, of, hemoglobin, throughout, mammals]), verbo([has]), complemento([made, the, laboratory, mouse, an, exceptionally, useful, organism, in, which, to, study, both, the, protein, and, the, individual, globin, genes])]). relacion([sujeto(['Early', researchers, looked, to, the, globin, genes, as, an, excellent, model, in, which, to, examine, gene, regulation, -, bountifully]), verbo([expressed]), complemento([and, displaying, a, remarkably, consistent, pattern, of, developmental, activation, and, silencing])]). relacion([sujeto(['In', parallel, with, the, growth, of, research, into, expression, of, the, globin, 'genes,', mutations, within, the, 'β-globin', gene, were, identified, as, the]), verbo([cause]), complemento([of, the, 'β-hemoglobinopathies', such, as, sickle, cell, disease, and, 'β-thalassemia'])]). relacion([sujeto(['These', lines, of, enquiry]), verbo([stimulated]), complemento([the, development, of, transgenic, mouse, 'models,', first, carrying, individual, human, globin, genes, and, then, substantial, human, genomic, fragments, incorporating, the, multigenic, human, 'β-globin', locus, and, regulatory, elements])]). relacion([sujeto(['These', years, of, work]), verbo([have]), complemento([generated, a, group, of, model, animals, that, display, many, features, of, the, 'β-hemoglobinopathies', and, provided, enormous, insight, into, the, mechanisms, of, gene, regulation])]). relacion([sujeto(['Substantive', differences, in, the, expression, of, human, and, mouse, globins, during, development]), verbo([have]), complemento([also, come, to, 'light,', revealing, the, limitations, of, the, mouse, 'model,', but, also, providing, opportunities, to, further, explore, the, mechanisms, of, globin, gene, regulation])]). relacion([sujeto(['In', 'addition,', animal, models, of, 'β-hemoglobinopathies']), verbo([have]), complemento([demonstrated, the, feasibility, of, gene, therapy, for, these, 'conditions,', now, showing, success, in, human, clinical, trials])]). relacion([sujeto(['Here,', we, describe, the, development, of, animal, models, to, investigate, globin, switching, and, the, 'β-hemoglobinopathies,', a, field, that]), verbo([has]), complemento([paralleled, the, emergence, of, modern, molecular, biology, and, clinical, genetics])]). relacion([sujeto(['We']), verbo([report]), complemento([the, case, of, a, 'nine-year-old', 'girl,', of, 'Moroccan', 'origin,', hospitalised, for, fever, and, stomach, ache])]). relacion([sujeto(['The', clinical, and, biological, investigations, showed, merely, a, moderate, enlargement, of, the, spleen]), verbo([associated]), complemento([with, discrete, regenerative, hemolytic, anemia])]). relacion([sujeto(['These', results]), verbo([led]), complemento([to, a, diagnosis, of, β0, thalassemia, associated, with, an, intermediate, 'phenotype,', i])]). relacion([sujeto([108, 'C>A)']), verbo([leading]), complemento([to, the, premature, stop, codon])]). relacion([sujeto(['The', study, of, several, polymorphisms]), verbo([involved]), complemento([in, the, regulation, of, the, expression, of, 'HbF', concords, with, the, intermediate, phenotype, found, in, the, patient])]). relacion([sujeto(['We']), verbo([have]), complemento(['isolated,', via, differential, hybridization, screening, of, a, floral, cDNA, library, from, 'sunflower,', a, cDNA, clone, that, hybridizes, to, a, 1100, 'nucleotide-long', mRNA, found, exclusively, in, mature, pollen, grains])]). relacion([sujeto(['A', similar, organization, is]), verbo([found]), complemento([in, the, 'erythroid-specific', transcription, factor, 'Eryf1', from, chicken, and, its, murine, homolog, 'GF-1'])]). relacion([sujeto(['These', features]), verbo([suggest]), complemento([that, the, 'SF3', protein, is, a, transcription, factor, required, for, the, expression, of, late, pollen, genes])]). relacion([sujeto(['A', genomic, copy, of, the, gene]), verbo([has]), complemento([been, isolated, and, 'sequenced;', it, is, split, by, four, 'short,', 'AT-rich', introns])]). relacion([sujeto(['We']), verbo([have]), complemento([cloned, the, gene, for, the, chicken, erythroid, transcription, factor, 'GATA-1', '(', formerly, 'Eryf1,', 'NF-E1,', or, 'GF-1)'])]). relacion([sujeto(['A', number, of, sequence, motifs, for, known, 'DNA-binding', proteins, are]), verbo([found]), complemento([to, be, protected, in, 'DNase', 'I-footprinting', experiments, by, either, erythroid, or, brain, nuclear, extracts, or, by, both])]). relacion([sujeto(['We']), verbo([find]), complemento([that, the, upstream, region, of, the, gene, functions, as, a, powerful, promoter, when, transfected, into, embryonic, erythroid, cells])]). relacion([sujeto(['In', primary, chicken, embryo, fibroblasts, the, promoter, exhibits, lower, 'activity,', which, is]), verbo([increased]), complemento([when, the, cells, are, cotransfected, with, a, second, plasmid, expressing, the, 'GATA-1', cDNA])]). relacion([sujeto(['The', results]), verbo([suggest]), complemento([that, 'GATA-1', protein, plays, an, autoregulatory, role, in, its, own, expression])]). relacion([sujeto(['The', areA, 'gene,']), verbo([mediating]), complemento([nitrogen, metabolite, repression, in, 'Aspergillus', 'nidulans,', encodes, a, 'positive-acting', regulatory, protein, with, a, single, putative, 'DNA-binding', '\'', zinc, 'finger\'', which, is, remarkably, similar, to, the, two, '\'', zinc, 'fingers\'', of, the, major, regulatory, protein, of, vertebrate, erythroid, cells, '(', 'GF-1/Eryf1/NF-E1)'])]). relacion([sujeto(['We']), verbo([have]), complemento([previously, reported, cloning, and, identification, of, the, human, 'gene,', 'HMT-1,', which, encodes, chitobiosyldiphosphodolichol, 'beta-mannosyltransferase', '(', 'β1,4-MT)', involved, in, the, early, assembly, of, 'DLO'])]). relacion([sujeto(['Here', we, screened, a, 1, &, 'nbsp;kb', region, upstream, from, 'HMT-1', open, reading, frame, '(', 'ORF)', for, transcriptionally, regulatory, sequences, by, using, chloramphenicol, acetyl, transferase, '(', 'CAT)', 'assay,', and]), verbo([found]), complemento([that, the, region, from, -, 33, to, -, 1, positions, might, act, in, 'HMT-1', transcription, at, basal, level, and, that, the, region, from, -, 200, to, -, 42, should, regulate, its, transcription, either, positively, or, negatively])]). relacion([sujeto(['In', 'addition,', results, with, 'CAT', assays]), verbo([suggested]), complemento([the, possibility, that, two, 'GATA-1', motifs, and, an, 'Sp1', motif, within, a, 200, &, 'nbsp;bp', region, upstream, from, 'HMT-1', 'ORF', might, significantly, upregulate, 'HMT-1', transcription])]). relacion([sujeto(['The', control, of, the, 'HMT-1', transcription, by, these, motifs, resided, within, the, 200, &, 'nbsp;bp', region, could, partially, explain, the, variation, of, expression, level, among, various, human, 'tissues,']), verbo([suggesting]), complemento([availability, and, importance, of, this, region, for, regulatory, role, in, 'HMT-1', expression])]). relacion([sujeto(['GATA-1,', a, zinc, finger, transcription, 'factor,']), verbo([has]), complemento([been, demonstrated, to, play, a, key, role, in, the, progression, of, leukemia])]). relacion([sujeto(['We']), verbo([found]), complemento([that, wogonoside, could, induce, growth, inhibition, and, 'G0/G1', cell, cycle, arrest, in, both, normal, and, 'K562r', cells])]). relacion([sujeto(['Wogonoside']), verbo([promotes]), complemento([the, expression, of, 'GATA-1', and, facilitates, the, binding, to, methyl, ethyl, ketone, '(', 'MEK)', and, p21, 'promoter,', thus, inhibiting, 'MEK/extracellular', 'signal-regulated', kinase, signaling, and, cell, cycle, checkpoint, 'proteins,', including, 'CDK2,', 'CDK4,', cyclin, 'A,', and, cyclin, 'D1,', and, increasing, p21, expression])]). relacion([sujeto(['Furthermore,', in, vivo, studies, showed, that, administration, of, wogonoside]), verbo([decreased]), complemento(['CML', cells, and, prolonged, survival, in, 'NOD/SCID', mice, with, 'CML', cell, xenografts])]). relacion([sujeto(['In', 'conclusion,', these, results, clearly, revealed, the, inhibitory, effect, of, wogonoside, on, the, growth, in, 'CML', cells, and]), verbo([suggested]), complemento([that, wogonoside, may, act, as, a, promising, drug, for, the, treatment, of, 'imatinib-resistant', 'CML'])]). relacion([sujeto(['In', inflamed, 'tissues,', eosinophils]), verbo([act]), complemento([as, key, mediators, of, terminal, effector, functions, and, innate, immunity, and, in, linking, to, adaptive, immune, responses])]). relacion([sujeto(['Elucidation', of, the, mechanism, of, eosinophil, development, and, activation, may]), verbo([lead]), complemento([to, selective, elimination, of, eosinophils, in, animals, and, human, subjects])]). relacion([sujeto(['α-Hemoglobin', stabilizing, protein, '(', 'AHSP)', is, a, small, protein, of, 102, residues]), verbo([induced]), complemento([by, 'GATA-1,', 'Oct-1-', and, 'EKLF'])]). relacion([sujeto(['It', is, synthesized, at, a, high, level, in, the, red, blood, cell, precursors, and]), verbo([acts]), complemento([as, a, chaperone, protecting, the, 'α-hemoglobin', '(', 'α-Hb)', chains, against, precipitation])]). relacion([sujeto(['α-Hemoglobin', stabilizing, protein, forms, a, heterodimer, complex, with, 'α-Hb,', then, displaying, modified, oxygen]), verbo([binding]), complemento([kinetics])]). relacion([sujeto(['In', the, absence, of, 'AHSP,', 'α-Hb', oxidizes, and, precipitates, within, the, erythrocyte, precursors, of, bone, marrow]), verbo([leading]), complemento([to, apoptosis, and, defective, erythropoiesis])]). relacion([sujeto(['Several', 'α-Hb', variants, with, a, structural, 'abnormality,', frequently, located, in, the, contact, area, between, 'α-Hb', and, 'AHSP,', exhibit, instability, and, a, 'thalassemia-like', syndrome, when, they, are]), verbo([associated]), complemento([with, another, 'α-thalassemia', '(', 'α-thal)', determinant])]). relacion([sujeto(['We']), verbo([suggest]), complemento([that, this, disorder, could, result, from, a, disturbed, interaction, between, the, abnormal, 'α-Hb', chains, and, 'AHSP'])]). relacion([sujeto(['Conversely,', it, was, hypothesized, from, studies, on, 'knock-out', 'mice,', that, a, defect, affecting, 'AHSP', could]), verbo([cause]), complemento([a, 'thalassemia-like', syndrome])]). relacion([sujeto(['This', was, supported, in, man, by, studies, showing, that, a]), verbo([decreased]), complemento([expression, of, 'AHSP', linked, to, specific, genetic, clades, could, act, as, a, modulating, factor, in, some, thalassemia, phenotypes])]). relacion([sujeto(['This', mutant, 'AHSP', was]), verbo([expressed]), complemento([in, vitro, and, demonstrated, by, biochemical, and, biophysical, studies, to, display, a, clear, defective, interaction, with, 'α-Hb,', which, could, support, the, hypothesis, that, the, reb, blood, cell, '(', 'RBC)', disorders, of, the, child, resulted, from, this, abnormality])]). relacion([sujeto(['It', therefore, appears, that, 'AHSP', is, a, factor, with, a, key, role, in, the, formation, of, 'Hb', tetramers, and, that, structural, 'abnormalities,', either, on, the, 'α-Hb', or, on, the, 'AHSP,', may]), verbo([act]), complemento([as, a, thalassemia, modulating, factor])]). relacion([sujeto(['In', malignant, 'haematopoiesis,', its, ectopic, expression, in, 'T', cells, is]), verbo([involved]), complemento([in, the, pathogenesis, of, leukaemia])]). relacion([sujeto(['LMO2', contains, four, 'zinc-finger', domains, and]), verbo([binds]), complemento([to, the, ubiquitous, nuclear, adaptor, protein, 'Ldb1', via, the, 'LIM-interaction', domain, '(', 'LID)'])]). relacion([sujeto(['Together,', they]), verbo([act]), complemento([as, scaffolding, proteins, and, bridge, important, haematopoietic, transcription, factors, such, as, 'SCL/Tal1,', 'E2A', and, 'GATA-1'])]). relacion([sujeto(['Solving', the, structure, of, the, 'LMO2:Ldb1-LID', complex, would, therefore, be, a, first, step, towards, understanding, how, haematopoietic, specific, protein, complexes, form, and, would, also]), verbo([provide]), complemento([an, attractive, target, for, drug, development, in, anticancer, 'therapy,', especially, for, 'T-cell', leukaemia])]). relacion([sujeto(['Multiple-wavelength', anomalous, dispersion, '(', 'MAD)', data]), verbo([have]), complemento([been, collected, at, the, zinc, 'X-ray', absorption, edge, to, a, resolution, of, 2.8, 'Å', and, the, data, were, used, to, solve, the, structure, of, the, 'LMO2:Ldb1-LID', complex])]). relacion([sujeto(['In', transgenic, mice, we, show, that, the, expression, of, 'HOXA10', is, tightly]), verbo([regulated]), complemento([by, doxycycline])]). relacion([sujeto(['Intermediate', concentrations, of, 'HOXA10']), verbo([induced]), complemento([a, 15, -, fold, increase, in, the, repopulating, capacity, of, hematopoietic, stem, cells, '(', 'HSCs)', after, 13, days, of, in, vitro, culture])]). relacion([sujeto(['The', 'HOXA10-mediated', effects, on, hematopoietic, cells, were]), verbo([associated]), complemento([with, altered, expression, of, genes, that, govern, 'stem-cell', 'self-renewal', and, lineage, commitment, '(', 'eg,', hepatic, leukemia, factor, '[', 'HlF],', 'Dickkopf-1', '[', 'Dkk-1],', growth, factor, 'independent-1', '[', 'Gfi-1],', and, 'Gata-1)'])]). relacion([sujeto(['Interestingly,']), verbo([binding]), complemento([sites, for, 'HOXA10', were, found, in, 'HLF,', 'Dkk-1,', and, 'Gata-1,', and, 'Dkk-1', and, 'Gfi-1', were, transcriptionally, activated, by, 'HOXA10'])]). relacion([sujeto(['These', findings]), verbo([reveal]), complemento([novel, molecular, pathways, that, act, downstream, of, 'HOXA10', and, identify, 'HOXA10', as, a, master, regulator, of, postnatal, hematopoietic, development])]). relacion([sujeto(['Alpha', hemoglobin, stabilizing, protein, '(', 'AHSP)', is, a, small, protein, of, 102, residues]), verbo([induced]), complemento([by, 'GATA-1,', 'Oct-1-', and, 'EKLF'])]). relacion([sujeto(['It', is, synthesized, at, a, high, level, in, the, red, blood, cell, precursors, and]), verbo([acts]), complemento([as, a, chaperone, protecting, the, alpha, hemoglobin, '(', 'alpha-Hb)', chains, against, precipitation])]). relacion([sujeto(['In', the, absence, of, 'AHSP,', 'alpha-Hb', oxidizes, and, precipitates, within, the, erythrocyte, precursors, of, the, bone, marrow]), verbo([leading]), complemento([to, apoptosis, and, defective, erythropoiesis])]). relacion([sujeto(['In', vitro, the]), verbo([binding]), complemento([of, 'AHSP', to, ferrous, 'alpha-Hb', accelerates, oxidation, of, the, heme, iron, in, 'alpha-Hb,', but, the, complex, is, more, resistant, to, protein, unfolding])]). relacion([sujeto(['AHSP', could]), verbo([act]), complemento([as, a, modulating, factor, in, 'beta-thalassemia'])]). relacion([sujeto(['Recent', studies, showed, more, severe, thalassemic, syndromes, in, patients, with]), verbo([decreased]), complemento([levels, of, 'AHSP', and, in, one, patient, who, carried, a, structurally, abnormal, 'AHSP'])]). relacion([sujeto(['We']), verbo([suggest]), complemento([that, this, could, result, from, a, disturbed, interaction, between, 'alpha-Hb', variants, and, 'AHSP'])]). relacion([sujeto(['Using', this, 'approach,', we, investigated, the, alpha42, '(', 'C7),', alpha104, '(', 'G11)', and, alpha119, '(', 'H2)', 'sites,', where, variants, with, some, thalassemic, features]), verbo([have]), complemento([been, described])]). relacion([sujeto(['We']), verbo([have]), complemento([constructed, 'Genetic', 'Regulatory', 'Networks', '(', 'GRNs)', describing, this, 'process,', based, predominantly, on, mouse, data])]). relacion([sujeto([coli, and, yeast, 'GRNs', are]), verbo([found]), complemento([in, combination, in, these, 'GRNs'])]). relacion([sujeto(['The', simultaneous, requirement, for, multiple, regulators, in, 'multi-input', motifs, '(', 'MIMs)']), verbo([provides]), complemento([tight, control, over, expression, of, target, genes])]). relacion([sujeto(['Combinations', of, 'MIMs,', exemplified, by, the, 'SCL/LMO2', 'complexes,', which]), verbo([have]), complemento([variable, content, and, binding, 'sites,', explain, how, individual, regulators, can, have, different, targets, in, 'HSCs', and, erythroid, cells, and, possibly, also, how, 'HSCs', maintain, stem, cell, functions, while, expressing, 'lineage-affiliated', genes, at, low, 'level,', 'so-called', 'multi-lineage', priming])]). relacion([sujeto([1, and, 'GATA-1', and, between, two, of, their]), verbo([target]), complemento(['genes,', 'Fli-1', and, 'EKLF,', with, victory, for, 'GATA-1', and, 'EKLF', leading, to, erythroid, lineage, specification])]). relacion([sujeto(['These', 'GRNs', are, useful, repositories, for, current, regulatory, 'information,', are, accessible, in, interactive, form, via, the, 'internet,', enable, the, consequences, of, perturbation, to, be, 'predicted,', and, can]), verbo([act]), complemento([as, seed, networks, to, organize, the, rapidly, accumulating, microarray, data])]). relacion([sujeto(['The', 5, '\'', -, flanking, region, of, the, first, exon]), verbo([has]), complemento([putative, elements, for, binding, transcription, factors, 'Sp-1,', 'GATA-1,', 'AML-1a,', 'Lyf-1', and, 'Ets-1,', but, there, were, no, 'TATA', or, 'CAAT', boxes, within, a, 226, -, bp, sequence, upstream, from, the, initiation, codon])]). relacion([sujeto(['We']), verbo([found]), complemento([that, 226, bp, of, the, core, promoter, region, exhibited, bidirectional, promoter, activity])]). relacion([sujeto(['The', results, showed, that, both, cell, lines]), verbo([expressed]), complemento(['LTAg', when, the, inducer, was, present, in, the, culture, media])]). relacion([sujeto(['After', 60, 'generations,', 'however,', the, continued, expression, of, 'LTAg', in, the, absence, of, the, hormone, indicated, that, unknown, changes, may]), verbo([have]), complemento([occurred, in, the, genome, of, the, cells])]). relacion([sujeto(['All', cell, lines]), verbo([expressed]), complemento([the, products, of, the, 'Sertoli', 'cell-specific', genes, stem, cell, factor, '(', 'SCF)', and, sulfated, 'glycoprotein-2', '(', 'SGP-2),', in, addition, to, 'alpha-inhibin,', 'GATA-1,', and, steroidogenic, 'factor-1'])]). relacion([sujeto(['Further,', the, lines]), verbo([express]), complemento([growth, and, differentiation, factors, known, to, act, upon, germ, cells, in, vivo, and, in, vitro, such, as, leukemia, inhibitory, factor, '(', 'LIF),', transforming, growth, factor, beta, '(', 'TGF-beta),', and, basic, fibroblast, growth, factor, '(', 'bFGF)'])]). relacion([sujeto(['Moreover,', when, used, as, feeder, layers, in, 'cocultures,', at, least, 2, of, these, lines, are, able, to]), verbo([maintain]), complemento([the, viability, of, type, 'A', spermatogonia, for, at, least, 7, days, and, to, support, the, first, steps, of, spermatogonial, differentiation])]). relacion([sujeto(['The', detailed, examination, of, the, molecular, events, that, control, the, early, stages, of, myeloid, differentiation]), verbo([has]), complemento([been, hampered, by, the, relative, scarcity, of, hematopoietic, stem, cells, and, the, lack, of, suitable, cell, line, models])]). relacion([sujeto(['Representational', difference, analysis, '(', 'RDA)', was, performed, to, identify, differentially]), verbo([expressed]), complemento([genes, in, 'EML'])]). relacion([sujeto(['In', a, search, for, genes, that, were, differentially]), verbo([expressed]), complemento([in, 'EML', cells, during, myeloid, 'differentiation,', six, cDNAs, were, isolated])]). relacion([sujeto(['The', identification, of, three, novel, 'genes,', two, of, which, encode, proteins, that, may]), verbo([act]), complemento([as, regulators, of, hematopoietic, 'differentiation,', suggests, that, 'EML', is, a, useful, model, system, for, the, molecular, analysis, of, hematopoietic, differentiation])]). relacion([sujeto(['They', are]), verbo([expressed]), complemento([exclusively, in, the, erythroid, 'cells,', only, during, defined, periods, of, development, and, in, a, perfectly, tuned, 'way,', 'assuring,', at, any, stage, of, 'ontogeny,', a, correct, balance, in, the, availability, of, 'a-', and, 'b-globin', chains, for, hemoglobin, assembling])]). relacion([sujeto(['All', these, sequences, exert, 'stimulatory,', inhibitory, or, more, complex, activities, by]), verbo([interacting]), complemento([with, transcription, factors, that, bridge, these, regions, of, 'DNA', to, the, 'RNA', polymerase, machinery])]). relacion([sujeto(['Many', of, these, factors]), verbo([have]), complemento([now, been, cloned, and, the, corresponding, mouse, genes, 'inactivated,', shading, new, light, on, the, metabolic, pathways, they, control])]). relacion([sujeto(['It', is, increasingly]), verbo([recognized]), complemento([that, such, factors, are, organized, into, hierarchies, according, to, the, number, of, genes, and, circuits, they, regulate])]). relacion([sujeto(['Some', genes, such, as, 'GATA-1', and, 2, are, master, regulators, that]), verbo([act]), complemento([on, large, numbers, of, genes, at, early, stage, of, differentiation, whereas, 'others,', like, 'EKLF,', stand, on, the, lowest, step, and, control, only, single, or, limited, number, of, genes, at, late, stages, of, differentiation])]). relacion([sujeto(['We']), verbo([have]), complemento([previously, described, the, isolation, of, 'primitive,', 'slow-proliferating', progenitors, from, 'normal,', circulating, 'CD34+', cells, by, using, the, fluorescent, dye, 5, -, 6, -, carboxyfluorescein, diacetate, succinimidyl, ester, '(', 'CFDA-SE)'])]). relacion([sujeto(['In', the, present, work, we, analysed, the, expression, levels, of, a, number, of, proteins]), verbo([involved]), complemento([with, 'differentiation,', proliferation, and, 'survival/apoptosis', in, 'CFDA-SE(bright)/CD34+/slow-proliferating', cells, that, were, previously, defined, as, progenitors, capable, of, differentiating, into, different, lineages])]). relacion([sujeto(['The', aim, of, this, work, was, to]), verbo([gain]), complemento([a, better, understanding, of, our, model, system, in, order, to, define, some, of, the, important, parameters, that, regulate, differentiation, in, haematopoietic, progenitors])]). relacion([sujeto([1, 'RNA', levels, were, similar, in, freshly, isolated, '(', d, 0, ')', 'CD34+', and, in, 'CFDA-SE(bright)', '(', 'bright)', 'cells,', whereas, they]), verbo([increased]), complemento([in, 'CFDA-SE(dim)', '(', 'dim)', cells])]). relacion([sujeto(['Accordingly,', 'Nm23', was]), verbo([expressed]), complemento([at, higher, levels, in, bright, cells])]). relacion([sujeto(['C-myc', and, p53, levels, were, higher, in, bright, cells, than, in, d, 0, 'CD34+', and, dim, 'cells,', and, so, was, 'Bcl-xL,', which, followed, the, trend, we]), verbo([have]), complemento([previously, described, for, 'Bcl-2'])]). relacion([sujeto(['Thus,', bright, 'cells,', despite, having, a, higher, proliferation, rate, than, the, starting, d, 0, 'CD34+', 'population,']), verbo([have]), complemento([strikingly, elevated, levels, of, 'cyclin-dependent', kinase, 'inhibitors,', which, are, likely, to, also, act, as, inhibitors, of, differentiation])]). relacion([sujeto(['FOG', is, a, multitype, zinc, finger, protein, that, is, essential, for, 'megakaryopoiesis,']), verbo([binds]), complemento([to, the, 'amino-terminal', finger, of, 'GATA-1,', and, modulates, the, transcription, of, 'GATA-1', target, genes])]). relacion([sujeto(['In', 'GATA-1-deficient', 'FDCER', cells, '(', in, the, presence, of, endogenous, 'FOG),', ectopically]), verbo([expressed]), complemento(['GATA-1', activated, transcription, 3, -, 10, -, fold, both, from, alpha, 'IIb', templates, and, the, endogenous, alpha, 'IIb', gene])]). relacion([sujeto(['The']), verbo([increased]), complemento([expression, of, 'FOG', increased, reporter, construct, transcription, 30, -, fold, overall])]). relacion([sujeto(['Unexpectedly,', alphaIIb, gene, transcription, also, was]), verbo([stimulated]), complemento([efficiently, upon, the, ectopic, expression, in, of, 'FOG', per, se])]). relacion([sujeto(['This', occurred, in, the, absence, of, any, detectable, expression, of, 'GATA-1', and, was, observed, in, multiple, independent, sublines, for, both, the, endogenous, alpha, 'IIb', gene, and, transfected, constructs, yet, proved, to, depend, largely, upon]), verbo([conserved]), complemento(['GATA', elements, 457, and, 55, base, pairs, upstream, from, the, transcriptional, start, site])]). relacion([sujeto(['In', 293, 'cells,', 'FOG', plus, 'GATA-1', but, not, 'FOG', alone, only, moderately]), verbo([stimulated]), complemento([alpha, 'IIb', 'transcription,', and, no, direct, interactions, of, 'FOG', with, the, alpha, 'IIb', promoter, were, detectable])]). relacion([sujeto(['Thus,', 'FOG']), verbo([acts]), complemento([in, concert, with, 'GATA-1', to, stimulate, alpha, 'IIb', expression, but, also, can, act, via, a, 'GATA-1-independent', 'route,', which, is, proposed, to, involve, additional, 'hematopoietic-restricted', cofactors, '(', possibly, 'GATA-2)'])]). relacion([sujeto(['In', a, heterologous, transcriptional, system, in, which, the, upstream, regions, of, oIFNtau, were, inserted, in, front, of, simian, virus, 40, '(', 'SV40)', 'promoter,', the, regions, between, bases, -, 654, and, -, 555, were, determined, as, being, the, enhancer, region]), verbo([required]), complemento([for, 'oIFNtau-SV40-CAT', transactivation])]). relacion([sujeto(['A', subsequent, study, with, the, 'oIFNtau-CAT', constructs, lacking, the, upstream, region, between, bases, -, 542, and, -, 124, revealed, 'that,', in, addition, to, the, further, upstream, region, between, bases, -, 1000, and, -, 654, ',', the, sequences, from, bases, -, 543, to, -, 452, seemed, to]), verbo([act]), complemento([as, silencer, regions])]). relacion([sujeto(['Furthermore,', gel, 'mobility-shift', assays, revealed, that, 'AP-1', or, other]), verbo([nuclear]), complemento([factors, could, bind, to, these, elements])]). relacion([sujeto(['In', 'co-transfection', 'studies,', the, expression, of, 'c-Jun', plus, 'c-Fos']), verbo([enhanced]), complemento([the, transactivation, of, 'oIFNtau-CAT', but, the, expression, of, 'GATA-1,', 'GATA-2', or, 'GATA-3', did, not])]). relacion([sujeto(['Taken', 'together,', these, results]), verbo([suggest]), complemento([that, the, upstream, region, between, bases, -, 654, and, -, 555, could, be, considered, as, the, enhancer, region, for, oIFNtau, gene, transactivation])]). relacion([sujeto(['We']), verbo([have]), complemento([previously, 'reported,', on, the, basis, of, transfection, 'experiments,', the, existence, of, a, silencer, element, in, the, 5, '\'', -, flanking, region, of, the, human, embryonic, '(', 'epsilon)', globin, 'gene,', located, at, -, 270, base, pairs, 5, '\'', to, the, cap, 'site,', which, provides, negative, regulation, for, this, gene])]). relacion([sujeto(['Experiments', in, transgenic, mice]), verbo([suggest]), complemento([the, physiological, importance, of, this, 'epsilon-globin', 'silencer,', but, also, suggest, that, 'down-regulation', of, 'epsilon-globin', gene, expression, may, involve, other, negative, elements, flanking, the, 'epsilon-globin', gene])]). relacion([sujeto(['We']), verbo([have]), complemento([now, extended, the, analysis, of, 'epsilon-globin', gene, regulation, to, include, the, flanking, region, spanning, up, to, 6, kilobase, pairs, 5, '\'', to, the, locus, control, region, using, reporter, gene, constructs, with, deletion, mutations, and, transient, transfection, assays])]). relacion([sujeto(['We']), verbo([have]), complemento([identified, and, characterized, other, strong, negative, regulatory, 'regions,', as, well, as, several, positive, regions, that, affect, transcription, activation])]). relacion([sujeto(['The', negative, regulatory, regions, at, -, 3, kilobase, pairs, '(', 'epsilonNRA-I', and, 'epsilonNRA-II),', flanked, by, a, positive, control, 'element,']), verbo([has]), complemento([a, strong, effect, on, the, 'epsilon-globin', promoter, both, in, erythroid, 'K562', and, nonerythroid, 'HeLa', cells, and, contains, several, binding, sites, for, transcription, factor, 'GATA-1,', as, evidenced, from, 'DNA-protein', binding, assays])]). relacion([sujeto(['Both', 'epsilonNRA-I', and, 'epsilonNRA-II', are, active, on, a, heterologous, promoter, and, hence, appear, to]), verbo([act]), complemento([as, transcription, silencers])]). relacion([sujeto(['Phylogenetic', 'DNA', sequence, comparisons, with, other, primate, and, other, mammalian, species, show, unusual, degree, of, flanking, sequence, homology, for, the, 'epsilon-globin', 'gene,', including, in, several, of, the, regions, identified, in, these, functional, and, 'DNA-protein']), verbo([binding]), complemento(['analyses,', providing, alternate, evidence, for, their, potential, importance])]). relacion([sujeto(['We']), verbo([suggest]), complemento([that, the, 'down-regulation', of, 'epsilon-globin', gene, expression, as, development, progresses, involves, 'complex,', cooperative, interactions, of, these, negative, regulatory, 'elements,', 'epsilonNRA-I/epsilonNRA-II,', 'epsilonNRB,', the, 'epsilon-globin', silencer, and, probably, other, negative, and, positive, elements, in, the, 5, '\'', -, flanking, region, of, the, 'epsilon-globin', gene])]). relacion([sujeto(['GATA', transcription, factors, are]), verbo([required]), complemento([for, the, differentiation, of, diverse, cell, types, in, several, species])]). relacion([sujeto(['Recent', evidence]), verbo([suggests]), complemento([that, their, biologic, activities, may, be, modulated, through, interaction, with, multitype, zinc, finger, 'proteins,', such, as, 'Friend', of, 'GATA-1', '(', 'FOG)', and, 'U-shaped', '(', 'Ush)'])]). relacion([sujeto(['In', cell, 'culture,', 'FOG', cooperates, with, the, hematopoietic, transcription, factor, 'GATA-1', to]), verbo([promote]), complemento([erythroid, and, megakaryocytic, differentiation])]). relacion([sujeto(['Although', the, 'FOG-/-', erythroid, phenotype, supports, the, proposed, role, of, 'FOG', as, a, 'GATA-1', cofactor, in, 'vivo,', the, latter]), verbo([finding]), complemento([points, to, a, 'pivotal,', 'GATA-1-independent', requirement, for, 'FOG', in, megakaryocyte, development, from, the, bipotential, 'erythroid/megakaryocytic', progenitor])]). relacion([sujeto(['We', speculate, that, 'FOG', and, other, 'FOG-like', proteins, serve, as, complex, cofactors, that]), verbo([act]), complemento([through, both, 'GATA-dependent', and, 'GATA-independent', mechanisms])]). relacion([sujeto(['Studies', of, hematopoietic, progenitor, cell, development, in, 'vivo,', ex, 'vivo,', and, in, 'factor-dependent', cell, lines]), verbo([have]), complemento([shown, that, 'c-kit', promotes, proliferation, through, synergistic, effects, with, at, least, certain, type, 1, cytokine, 'receptors,', including, the, erythropoietin, '(', 'Epo)', receptor])]). relacion([sujeto(['In', this, 'system,', mitogenic, synergy, with, 'c-kit', was, observed, for, ectopically]), verbo([expressed]), complemento(['wild-type', 'Epo', receptors, '(', 'wt-ER),', an, epidermal, growth, factor, '(', 'EGF)', 'receptor/Epo', receptor, 'chimera,', and, a, highly, truncated, 'Epo', receptor, construct, 'ER-Bx1'])]). relacion([sujeto(['Thus,', the, 'Epo', receptor, cytoplasmic, box, 1, subdomain, 'appears,', at, least, in, 'part,', to]), verbo([mediate]), complemento([mitogenic, synergy, with, 'c-kit'])]). relacion([sujeto(['In', studies, of, potential, effectors, of, this, 'response,', 'Jak2', tyrosine, phosphorylation, was, shown, to, be]), verbo([induced]), complemento([by, 'Epo,', but, not, by, stem, cell, factor, '(', 'SCF)'])]). relacion([sujeto(['In', addition, and, in, contrast, to, signaling, in, 'Mo7e', and, 'BM6', cell, 'lines,', in, 'FDC2-ER', cells, 'SCF', and, 'Epo', each, were, shown, to, rapidly]), verbo([activate]), complemento(['Pim', 1, gene, expression])]). relacion([sujeto(['Recently,', roles, also]), verbo([have]), complemento([been, suggested, for, the, nuclear, 'trans-factor', 'GATA-1', in, regulating, progenitor, cell, proliferation])]). relacion([sujeto(['However,', 'GATA-1', expression, did, result, in, a, selective, and, marked, inhibition, in, mitogenic, responsiveness, to, 'SCF', and, to, a]), verbo([decrease]), complemento([in, 'c-kit', transcript, expression])]). relacion([sujeto(['These', studies, of, 'SCF', and, 'Epo', signaling, in, 'FDC2-wt-ER', cells, serve, to, functionally, map, the, 'ERB1', region, as, a, 'c-kit-interactive', 'domain,']), verbo([suggest]), complemento([that, 'Pim1', might, contribute, to, 'SCF', and, 'Epo', mitogenic, synergy, and, support, the, notion, that, 'SCF', and, 'Epo', may, act, in, opposing, ways, during, red, cell, differentiation])]). relacion([sujeto(['In', this, 'system,', enhancers]), verbo([act]), complemento([primarily, to, increase, the, probability, of, rapid, and, efficient, transcription, complex, formation, and, initiation])]). relacion([sujeto(['Repressor', and, activator, proteins]), verbo([binding]), complemento([within, the, 'promoter,', including, 'erythroid-specific', 'GATA-1,', mediate, this, process])]). relacion([sujeto(['Xenopus', 'GATA-6', transcripts, are, first, detected, at, the, beginning, of, gastrulation, in, the, 'mesoderm,', and, subsequent, domains, of, expression, include, the, field, of, cells, shown, to]), verbo([have]), complemento(['heart-forming', potential])]). relacion([sujeto(['In', this, 'region,', 'GATA-6', expression, continues, only, in, those, cells, that, go, on, to, form, the, 'heart;', 'however,', a]), verbo([decrease]), complemento([occurs, prior, to, terminal, differentiation])]). relacion([sujeto(['Artificial', elevation, of, 'GATA-6,', but, not, 'GATA-1,']), verbo([prevents]), complemento([expression, of, both, cardiac, actin, and, 'heart-specific', myosin, light, chain])]). relacion([sujeto(['We', conclude, that, a, reduction, in, the, level, of, 'GATA-6', is, important, for, the, progression, of, the, cardiomyogenic, differentiation, programme, and, that, 'GATA-6', may]), verbo([act]), complemento([to, maintain, heart, cells, in, the, precursor, state])]). relacion([sujeto(['At', later, 'stages,', when, the, elevated, 'GATA-6', levels, had, 'decayed,', differentiation, ensued, but, the, number, of, cells, contributing, to, the, myocardium, had, 'increased,']), verbo([suggesting]), complemento([either, that, the, blocked, cells, had, proliferated, or, that, additional, cells, had, been, recruited])]). relacion([sujeto(['To', study, the, process, of, blood, formation, during, vertebrate, development, we]), verbo([have]), complemento([used, the, expression, of, these, 'GATA', factors, to, locate, haematopoietic, cells, in, 'Xenopus', embryos, and, to, act, as, sensors, for, the, effects, of, 'all-trans', retinoic, acid, '(', 'RA),', a, signalling, molecule, which, influences, both, anteroposterior, patterning, and, haematopoietic, differentiation])]). relacion([sujeto(['GATA', factor, expression, was, detected, in, the]), verbo([leading]), complemento([edge, of, the, gastrulating, 'mesoderm,', in, the, ventral, blood, island, '(', 'VBI)', and, dorsolateral, plate, '(', 'DLP)', mesoderms, and, in, a, population, of, cells, between, the, 'VBI', and, 'DLP'])]). relacion([sujeto(['The', 'VBI', contributes, to, both, embryonic, and, adult, 'blood,', whereas, the, 'DLP', contains, precursors, of, adult, blood, 'only,', which]), verbo([have]), complemento([not, been, identified, previously, with, molecular, markers])]). relacion([sujeto(['Differential', effects, of, 'RA', on, the, expression, of, 'GATA-1', and, 'GATA-2']), verbo([suggest]), complemento([that, 'RA', has, a, direct, action, on, haematopoietic, 'differentiation,', rather, than, on, the, formation, of, haematopoietic, mesoderm])]). relacion([sujeto(['Our', studies, of, the, promoters, of, the, myeloid, 'CSF', receptors, '(', 'M,', 'GM,', and, 'G)', in, cell, lines]), verbo([have]), complemento([led, to, the, findings, that, the, promoters, are, 'small,', and, are, all, activated, by, the, 'PU'])]). relacion([sujeto(['To', 'date,', we]), verbo([have]), complemento([only, found, evidence, for, involvement, of, 'C/EBP', 'alpha,', although, further, experiments, will, be, needed, to, exclude, the, role, of, 'C/EBP', beta, and, 'C/EBP', delta, in, receptor, gene, expression])]). relacion([sujeto(['These', studies]), verbo([suggest]), complemento([a, model, of, hematopoiesis, '(', 'Fig'])]). relacion([sujeto([2, ')', in, which, the, lineage, commitment, decisions, of, multipotential, cells, are, made, by, the, alternative, patterns, of, expression, of, certain, transcription, 'factors,', which, then]), verbo([activate]), complemento([growth, factor, receptors, which, allow, those, cells, to, respond, to, the, appropriate, growth, factor, to, proliferate, and, survive])]). relacion([sujeto(['For', 'example,', expression, of, 'GATA-1']), verbo([activates]), complemento([its, own, 'expression,', as, well, as, that, of, the, erythropoietin, 'receptor,', inducing, these, cells, to, be, capable, of, responding, to, erythropoietin])]). relacion([sujeto([1]), verbo([activates]), complemento([its, own, 'promoter,', and, turns, on, the, three, myeloid, 'CSF', receptors, '(', 'M,', 'GM,', and, 'G),', pushing, these, cells, along, the, pathway, of, myeloid, differentiation])]). relacion([sujeto(['C/EBP', 'proteins,', particularly, 'C/EBP', 'alpha,', are, also, critical, for, myeloid, receptor, promoter, 'function,', and, may, also]), verbo([act]), complemento([via, autoregulatory, mechanisms])]). relacion([sujeto(['Murine', 'C/EBP', alpha]), verbo([has]), complemento([a, 'C/EBP', binding, site, in, its, own, promoter])]). relacion([sujeto(['Human', 'C/EBP', alpha, autoregulates, its, own, expression, in, adipocytes, by]), verbo([activating]), complemento([the, 'USF', transcription, factor])]). relacion([sujeto(['Myeloid', genes]), verbo([expressed]), complemento([later, during, 'differentiation,', such, as, 'CD11b,', are, also, activated, by, 'PU'])]). relacion([sujeto([1, ',', which, is]), verbo([expressed]), complemento([at, highest, levels, in, mature, myeloid, 'cells,', but, not, by, 'C/EBP', 'alpha,', which, is, downregulated, in, a, differentiated, murine, myeloid, cell, line])]). relacion([sujeto([1, in, erythroid, cells, blocks, erythroid, 'differentiation,']), verbo([leading]), complemento([to, 'erythroleukemia,', and, overexpression, of, 'GATA-1', in, a, myeloid, line, blocks, myeloid, differentiation])]). relacion([sujeto(['While', these, findings]), verbo([have]), complemento([provided, some, framework, for, understanding, myeloid, gene, 'regulation,', there, are, a, number, of, critical, questions, to, be, addressed, in, the, near, 'future:', 'What', is, the, pattern, of, expression, of, the, 'C/EBP', proteins, during, the, course, of, myeloid, differentiation, and, activation, of, human, 'CD34+', 'cells?', 'What', is, the, effect, of, targeted, disruption, and, other, mutations, of, the, 'C/EBP', and, 'AML1', proteins, on, myeloid, development, and, receptor, 'expression?', 'What', are, the, interactions, among, these, three, different, types, of, factors, '(', 'ets,', basic, 'region-zipper,', and, 'Runt', domain, 'proteins)', to, activate, the, 'promoters?', 'What', is, the, effect, of, 'translocations,', 'mutations,', and, alterations, in, expression, of, these, 'factors,', particularly, in, different, forms, of, 'AML?', 'To', elucidate, the, mechanisms, underlying, the, 'tissue-restricted', expression, of, 'GATA', factor, 'transcription,', we, have, isolated, and, analyzed, the, genomic, chicken, 'GATA-3', '(', 'cGATA-3)', locus])]). relacion([sujeto(['Two', 'trans-activating', domains, and, two, 'Zn', finger, domains, of, 'cGATA-3', were]), verbo([found]), complemento([to, be, encoded, separately, by, exons, 2, /, 3, and, 4, /, 5, ',', 'respectively,', indicating, that, each, functional, domain, of, 'GATA-3', is, encoded, by, a, discrete, exon])]). relacion([sujeto(['We']), verbo([have]), complemento([determined, 1.7, kb, of, upstream, promoter, sequence, and, found, a, number, of, sequence, motifs, which, match, those, of, known, transcription, factor, binding, sites])]). relacion([sujeto(['The', upstream, region, containing, the, 'GATA', and, 'CACCC', elements, in, close, proximity, '(', -, 1280, to, -, 1152, ')', appeared, to]), verbo([act]), complemento([as, a, negative, transcriptional, 'regulator,', whereas, the, region, -, 1151, to, -, 850, acts, as, a, positive, regulator])]). relacion([sujeto(['Thus,', the, expression, of, 'cGATA-3', gene, is, under, complex, regulation, and, the, mode, of, regulation, of, 'cGATA-3', gene, expression, is]), verbo([suggested]), complemento([to, be, different, from, that, of, 'GATA-1', genes])]). relacion([sujeto(['The', gene, pannier]), verbo([acts]), complemento([as, a, repressor, of, achaete, and, 'scute,', two, transcription, factors, expressed, in, discrete, subsets, of, cells, at, the, sites, where, neural, precursors, develop])]). relacion([sujeto(['Mutants']), verbo([associated]), complemento([with, lesions, in, the, zinc, finger, domain, display, an, overexpression, of, achaete, and, scute, and, the, development, of, extra, neural, precursors])]). relacion([sujeto(['Mutant', proteins, in, which, the, domain, including, the, putative, helices, is, deleted]), verbo([act]), complemento([as, hyperactive, repressor, molecules, causing, a, loss, of, 'achaete/scute', expression, and, a, loss, of, neural, precursors])]). relacion([sujeto(['Other', results]), verbo([suggest]), complemento([that, the, activity, of, pannier, may, be, modulated, by, association, with, 'position-specific', factors])]). relacion([sujeto(['GATA-1,', a, transcription, factor, of, the, '\'', 'zinc-finger\'', 'family,', is]), verbo([required]), complemento([for, the, development, of, mature, erythroid, cells, and, is, also, highly, expressed, in, the, megakaryocytic, and, mast, cell, lineages])]). relacion([sujeto(['The', 'helix-loop-helix', gene, 'SCL', '(', or, 'TAL)', is]), verbo([expressed]), complemento([in, the, same, three, hematopoietic, lineages, as, 'GATA-1'])]). relacion([sujeto(['Enforced', expression, of, 'SCL', at, high, levels, did, not]), verbo([provoke]), complemento(['differentiation,', but, 'GATA-1', induced, the, appearance, of, megakaryocytes, as, assessed, by, 'morphology,', the, presence, of, acetylcholinesterase, and, a, polyploid, 'DNA', content])]). relacion([sujeto(['Although', 'GATA-1', is, thought, to]), verbo([stimulate]), complemento([its, own, transcription, in, 'erythrocytes,', expression, of, the, endogenous, gene, was, not, increased, in, the, megakaryocytic, 'lines;', hence, 'GATA-1', may, not, be, autoregulatory, in, this, lineage])]). relacion([sujeto(['Megakaryocytic', differentiation, was, accompanied, by, a, marked]), verbo([decrease]), complemento([in, the, myeloid, surface, marker, 'Mac-1'])]). relacion([sujeto(['The', absence, of, mast, cell, or, erythroid, differentiation]), verbo([suggests]), complemento([that, 'GATA-1', may, not, be, sufficient, to, provoke, maturation, along, these, lineages, or, that, these, pathways, are, impeded, in, 416, 'B', cells])]). relacion([sujeto(['These', results, demonstrate, that, a, member, of, the, 'GATA', gene, family, can]), verbo([act]), complemento([as, an, important, regulator, of, megakaryocytic, differentiation])]). relacion([sujeto(['Colony-forming', assays, were, used, to, investigate, the, effects, of, 'PDCD2']), verbo([loss]), complemento([on, 'HPC', clonogenic, potential, and, on, 12, -, 'O-tetradecanoyl-phorbol-13-acetate-and', 'arabinofuranosylcytosine-induced', terminal, differentiation])]). relacion([sujeto(['In', 'CD34(+)', clonogenic, 'progenitors,', 'PDCD2', knockdown]), verbo([decreased]), complemento([the, total, number, of, 'colony-forming', 'units,', increased, the, number, of, 'colony-forming', 'units-granulocyte-erythroid-macrophage-megakaryocyte', and, 'burst-forming', 'unit-erythroid', primitive, 'colonies,', and, decreased, the, number, of, 'burst-forming', 'unit-erythroid', mature, colonies])]). relacion([sujeto(['Similar', results, were, observed, in, 'K562', 'cells,']), verbo([suggesting]), complemento([that, 'PDCD2', is, important, for, 'HPC', differentiation, 'and/or', 'survival,', and, for, erythroid, lineage, commitment])]). relacion([sujeto(['The', effects, of, 'PDCD2', knockdown, were, attributed, to, a, cell, cycle]), verbo([arrest]), complemento([at, 'G(0)/G(1),', along, with, increased, messenger, 'RNA', expression, of, early, progenitor, factors, 'c-MYB', and, 'GATA-2,', and, decreased, expression, of, erythroid, factors, 'GATA-1,', 'EpoR,', and, 'γ-globin'])]). relacion([sujeto(['We', conclude, that, 'PDCD2']), verbo([loss]), complemento([of, 'function(s)', impedes, erythroid, differentiation, by, inducing, cell, cycle, arrest, and, increasing, expression, of, early, hematopoietic, progenitor, factors])]). relacion([sujeto(['These', findings]), verbo([suggest]), complemento([that, 'PDCD2', has, a, novel, regulatory, role, in, human, hematopoiesis, and, is, essential, for, erythroid, development])]). relacion([sujeto(['Gel', filtration, chromatography, confirms, the, 'differentiation-dependent']), verbo([binding]), complemento([and, shows, that, it, correlates, with, the, assembly, of, a, complex, also, containing, the, key, megakaryocyte, transcription, factors, 'GATA-1', and, 'Friend', of, 'GATA-1', '(', 'FOG-1)'])]). relacion([sujeto(['Phosphorylation', analysis, of, 'FLI-1', with, uninduced, versus]), verbo([induced]), complemento(['L8057', cells, suggests, the, loss, of, phosphorylation, at, serine, 10, in, the, induced, state])]). relacion([sujeto(['Substitution', of, 'Ser10', with, the, phosphorylation, mimic, aspartic, acid, selectively, impairs, 'RUNX-1', 'binding,', abrogates, transcriptional, synergy, with, 'RUNX-1,', and, dominantly]), verbo([inhibits]), complemento([primary, fetal, liver, megakaryocyte, differentiation, in, vitro])]). relacion([sujeto(['These', findings]), verbo([have]), complemento([implications, for, other, cell, types, where, interactions, between, runx, and, ets, family, proteins, occur])]). relacion([sujeto(['CHRF', cells, constitutively]), verbo([express]), complemento([some, early, 'Mk', genes, including, 'GATA-1'])]). relacion([sujeto(['Expression', patterns, of, 'apoptosis-related', genes]), verbo([suggested]), complemento([that, increased, p53, activity, is, involved, in, 'Mk', 'apoptosis,', and, this, was, confirmed, by, 'p53-DNA-binding', activity, data, and, 'flow-cytometric', analysis, of, the, p53, target, gene, 'BBC3'])]). relacion([sujeto(['Certain', 'Rho', and, 'G-protein-coupled-receptor', signaling, pathway, components, were, 'upregulated,', including, genes, not, previously]), verbo([associated]), complemento([with, 'Mk', cells])]). relacion([sujeto(['This', analysis, of, 'megakaryopoiesis,', which, integrates, dynamic, gene, expression, data, with, protein, abundance, and, activity, 'assays,']), verbo([has]), complemento([identified, a, number, of, genes, and, pathways, that, may, help, govern, megakaryopoiesis])]). relacion([sujeto(['Thrombospondin-1', '(', 'TSP-1),', a, multifunctional, extracellular, matrix, 'protein,']), verbo([inhibits]), complemento([neovascularization, and, is, implicated, in, the, regression, of, tumor, growth, and, metastasis])]). relacion([sujeto(['We']), verbo([found]), complemento([that, the, synthesis, of, 'TSP-1', in, porcine, aortic, endothelial, '(', 'PAE)', cells, was, decreased, in, a, 'dose-dependent', manner, by, phorbol, 12, -, myristate, 13, -, acetate, '(', 'PMA)', treatment, in, porcine, aortic, endothelial, '(', 'PAE)', cells])]). relacion([sujeto(['The', level, of, 'TSP-1', mRNA, was, also]), verbo([decreased]), complemento([by, 'PMA', after, 1, h, and, persisted, that, way, for, at, least, 24, h])]). relacion([sujeto(['PMA', treatment, and, 'c-Jun', overexpression]), verbo([suppressed]), complemento([the, transcription, of, 'TSP-1', 'promotor-luciferase', reporter, gene])]). relacion([sujeto(['Electrophoretic', mobility, shift, assays, showed, that, this, 'PMA', responsive, element, specifically]), verbo([bound]), complemento([a, nuclear, protein, and, that, the, binding, activity, was, diminished, by, 'PMA', treatment, in, 'PAE', cells, but, not, in, 'Hep', 3, 'B', cells])]). relacion([sujeto(['Our', results]), verbo([suggest]), complemento([that, the, repression, of, 'TSP-1', synthesis, by, 'PMA', is, mediated, by, blocking, a, particular, unknown, nuclear, protein, binding, to, the, responsive, site, '(', -, 767, approximately, -, 735, ')', ',', which, is, regulated, by, 'c-Jun'])]). relacion([sujeto(['We']), verbo([have]), complemento([previously, shown, that, the, transcriptional, cofactor, 'CREB-binding', protein, '(', 'CBP)', binds, to, the, zinc, finger, domain, of, 'GATA-1,', markedly, stimulates, the, transcriptional, activity, of, 'GATA-1,', and, is, required, for, erythroid, differentiation])]). relacion([sujeto(['Here', we]), verbo([report]), complemento([that, 'CBP,', but, not, 'p/CAF,', acetylates, 'GATA-1', at, two, highly, conserved, 'lysine-rich', motifs, present, at, the, 'C-terminal', tails, of, both, zinc, fingers])]). relacion([sujeto(['In', 'addition,', we, show, that, 'CBP']), verbo([stimulates]), complemento(['GATA-1', acetylation, in, vivo, in, an, 'E1A-sensitive', 'manner,', thus, establishing, a, correlation, between, acetylation, and, transcriptional, activity, of, 'GATA-1'])]). relacion([sujeto(['Acetylation', in, vitro, did, not, alter, the, ability, of, 'GATA-1', to]), verbo([bind]), complemento(['DNA,', and, mutations, in, either, motif, did, not, affect, 'DNA', binding, of, 'GATA-1', expressed, in, mammalian, cells])]). relacion([sujeto(['Since', certain, functions, of, 'GATA-1', are, revealed, only, in, an, erythroid, 'environment,', 'GATA-1', constructs, were, examined, for, their, ability, to]), verbo([trigger]), complemento([terminal, differentiation, when, introduced, into, a, 'GATA-1-deficient', erythroid, cell, line])]). relacion([sujeto(['We']), verbo([found]), complemento([that, mutations, in, either, acetylation, motif, partially, impaired, the, ability, of, 'GATA-1', to, induce, differentiation, while, mutations, in, both, motifs, abrogated, it, completely])]). relacion([sujeto(['Taken', 'together,', these, data, indicate, that, 'CBP', is, an, important, cofactor, for, 'GATA-1', and]), verbo([suggest]), complemento([a, novel, mechanism, in, which, acetylation, by, 'CBP', regulates, 'GATA-1', activity, in, erythroid, cells])]). relacion([sujeto(['Thrombopoietin', '(', 'TPO)']), verbo([regulates]), complemento([megakaryocytic, '(', 'MK)', maturation, and, platelet, production])]). relacion([sujeto(['The', erythroid, differentiation, of, both, cell, lines, can, be, markedly]), verbo([increased]), complemento([by, 'EPO'])]). relacion([sujeto(['Several', 'UT-7/c-mpl', and, 'TF-1/c-mpl', cell, clones, which]), verbo([express]), complemento([different, levels, of, the, 'c-mpl', protein, '(', 'Mpl)', were, obtained, and, all, became, 'TPO-dependent', for, their, proliferation])]). relacion([sujeto(['This', was, demonstrated, by, the]), verbo([increase]), complemento([in, 'MK', markers, '(', 'GPIIb,', 'GPIIIa,', 'GPIb', 'alpha,', 'GPIX', and, 'vWF),', the, appearance, of, cytoplasmic, 'alpha-granules,', intracellular, membranes, resembling, demarcation, membranes, which, were, immunologically, labeled, with, an, 'GPIIb/IIIa', 'anti-antibody,', and, a, small, percentage, of, polyploid, cells, '(', 8, 'N', and, 16, 'N)'])]). relacion([sujeto(['In', 'contrast,', 'TPO']), verbo([inhibited]), complemento([the, erythroid, program, of, differentiation, '(', glycophorin, 'A,', 'beta-globin', and, 'EPO', 'receptor)', as, well, as, the, differentiative, activity, of, 'EPO', in, both, 'UT-7/c-mpl', and, 'TF-1/c-mpl', clones])]). relacion([sujeto(['It', is, noteworthy, that, the, differentiative, effect, of, 'EPO', in, 'TF-1/c-mpl', cells, was]), verbo([associated]), complemento([with, an, increase, in, 'GATA-1', transcripts, which, was, totally, suppressed, by, 'TPO'])]). relacion([sujeto(['Overall', the, effects, of, 'TPO', are, the, same, as, those, of, phorbol, myristate, acetate, '(', 'PMA)', which, also]), verbo([induces]), complemento(['MK', differentiation, and, inhibits, erythroid, differentiation])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento(['that:', '(', 1, ')', 'Mpl', expression, is, necessary, but, not, sufficient, for, induction, of, 'MK', 'differentiation;', and, '(', 2, ')', induction, of, 'Mk', differentiation, and, inhibition, of, erythroid, differentiation, by, 'TPO', involve, different, signaling, 'pathways;', the, pathway, involved, in, the, inhibition, of, erythroid, differentiation, might, be, related, to, a, downregulation, of, 'GATA-1', expression, in, 'TF-1', cells])]). relacion([sujeto(['Erythropoietin', '(', 'Epo)', is, a, cytokine, known, to]), verbo([stimulate]), complemento([proliferation, and, differentiation, of, erythroid, cells])]). relacion([sujeto(['Accompanying', this, cell, 'death,', an]), verbo([increase]), complemento([in, the, number, of, 'hemoglobin-positive', cells, of, approximately, 2, -, fold, was, observed])]). relacion([sujeto(['This', was]), verbo([associated]), complemento([with, immediate, 'up-regulation', of, the, 'GATA-1:GATA-2', ratio, and, 'down-regulation', of, 'Bcl-xL'])]). relacion([sujeto(['Treatment', with, 'Epo', or, 12, -, 'O-tetradecanoyl-phorbol-13-acetate', '(', 'TPA)', 'up-regulated', expression, of, 'GATA-2', and, 'Bcl-xL,', and, these, elevations, were]), verbo([inhibited]), complemento([by, inhibitors, of, protein, kinase, 'C', '(', 'PKC),', 'H7', and, 'H8'])]). relacion([sujeto(['Therefore,', in, 'AS-E2', 'cells,', it, is, likely, that, 'Epo', plays, a, role, in, '(', 'a)', 'proliferation,', '(', 'b)', inhibition, of, 'differentiation,', and, '(', 'c)', 'survival,', by]), verbo([maintaining]), complemento(['GATA-2', and, 'Bcl-xL', expression, through, activation, of, 'PKC'])]). relacion([sujeto(['However,', ectopic, expression, of, a, conditional, 'GATA-2/estrogen', receptor, chimera, was, shown, to]), verbo([inhibit]), complemento([erythroid, differentiation, in, a, 'hormone-dependent', 'manner,', suggesting, the, negative, regulation, of, erythroid, differentiation, by, 'GATA-2', protein])]). relacion([sujeto(['On', the, basis, of, these, 'measurements,', we, show, that, 'TPA-induced']), verbo([arrest]), complemento([of, erythroid, differentiation, is, coupled, with, the, upregulation, of, 'GATA-2', 'protein,', as, well, as, the, downregulation, of, 'GATA-1', protein])]). relacion([sujeto(['Our', results]), verbo([suggest]), complemento([that, it, is, the, precise, quantitative, balance, of, 'GATA-1', and, 'GATA-2', protein, that, regulates, erythroid, differentiation])]). relacion([sujeto(['Oxidative', stress]), verbo([has]), complemento([been, implicated, as, a, cause, of, various, diseases, such, as, anaemia])]). relacion([sujeto(['We']), verbo([found]), complemento([that, the, 'SOD1', '[', 'Cu,Zn-SOD', '(', superoxide, 'dismutase)]', gene, deficiency, causes, 'anaemia,', the, production, of, autoantibodies, against, 'RBCs', '(', red, blood, 'cells)', and, renal, damage])]). relacion([sujeto(['In', the, present, 'study,', to, further, understand, the, role, of, oxidative, stress, in, the, autoimmune, response]), verbo([triggered]), complemento([by, 'SOD1', 'deficiency,', we, generated, mice, that, had, the, hSOD1, '(', human, 'SOD1)', transgene, under, regulation, of, the, 'GATA-1', 'promoter,', and, bred, the, transgene, onto, the, 'SOD1(-/-)', background, '(', 'SOD1(-/-);hSOD1(tg/+))'])]). relacion([sujeto(['The', production, of, antibodies, against, lipid, peroxidation, 'products,', 4, -, 'hydroxy-2-nonenal', and, 'acrolein,', as, well, as, autoantibodies, against, 'RBCs', and, carbonic, anhydrase, 'II', were, elevated, in, the, 'SOD1(-/-)', 'mice,', but, were]), verbo([suppressed]), complemento([in, the, 'SOD1(-/-);hSOD1(tg/+)', mice])]). relacion([sujeto(['Metabolomic', analysis, indicated, a, shift, in, glucose, metabolism, to, the, pentose, phosphate, pathway, and, a]), verbo([decrease]), complemento([in, the, energy, charge, potential, of, 'RBCs', in, 'SOD1-deficient', mice])]). relacion([sujeto(['We', conclude, that, the]), verbo([increase]), complemento([in, reactive, oxygen, species, due, to, 'SOD1', deficiency, accelerates, 'RBC', destruction, by, affecting, carbon, metabolism, and, increasing, oxidative, modification, of, lipids, and, proteins])]). relacion([sujeto(['The', resulting, oxidation, products, are, antigenic, 'and,', 'consequently,']), verbo([trigger]), complemento([autoantibody, 'production,', leading, to, autoimmune, responses])]). relacion([sujeto(['Here,', we, illustrate, that, 'DC-SCRIPT', is, highly]), verbo([conserved]), complemento([in, evolution, and, report, the, initial, characterization, of, the, murine, ortholog, of, 'DC-SCRIPT,', which, is, also, preferentially, expressed, in, 'DC', as, shown, by, 'real-time', quantitative, polymerase, chain, 'reaction,', and, its, distribution, resembles, that, of, its, human, counterpart])]). relacion([sujeto(['Studies', undertaken, in, human, embryonic, kidney, 293, cells, depict, its]), verbo([nuclear]), complemento([localization, and, reveal, that, the, 'Zn', finger, domain, of, the, protein, is, mainly, responsible, for, nuclear, import])]). relacion([sujeto(['XPA,', an, essential, protein, in, nucleotide, excision, repair, '(', 'NER),']), verbo([interacts]), complemento([with, damaged, 'DNA', and, other, proteins, '(', 'RPA,', 'ERCC1', and, 'TFIIH)', to, remove, a, wide, variety, of, chemically, and, structurally, distinct, 'DNA', lesions, from, the, eukaryotic, genome])]). relacion([sujeto(['To', understand, the, structural, basis, for, the, role, of, 'XPA', in, the, repair, 'process,', the, structure, of, the, minimal, 'DNA']), verbo([binding]), complemento([domain, of, human, 'XPA', '[', 'XPA-MBD', '(', 'M98-F219)]', was, studied, by, 'NMR', spectroscopy])]). relacion([sujeto(['The', 'zinc-associated', core, contains, an, antiparallel, 'beta-sheet', '(', 'Y102-C105', and, 'K110-M113)', and, an, 'alpha-helix', '(', 'C126-K137)', separated, by, a, poorly, defined, 'turn,', reminiscent, of, the, structure, of, the, 'zinc-binding', domain, of, the, chicken, erythroid, transcription, factor, 'GATA-1', when]), verbo([bound]), complemento([to, its, cognate, 'DNA', sequence])]). relacion([sujeto(['The', 'XPA-MBD', structure, is, discussed, in, terms, of, known, 'functions:']), verbo([binding]), complemento(['single-', and, 'double-stranded', 'DNA', and, binding, 'RPA'])]). relacion([sujeto(['A', change, of, a, universally]), verbo([conserved]), complemento([leucine, to, valine, in, the, 'DNA-binding', domain, of, the, 'GATA', factor, 'AreA', results, in, inability, to, activate, some, 'AreA-dependent', 'promoters,', including, that, of, the, uapA, gene, encoding, a, specific, 'urate-xanthine', permease])]). relacion([sujeto(['In', vitro]), verbo([binding]), complemento([studies, of, 'wild-type', and, mutant, 'AreA', proteins, are, completely, consistent, with, the, phenotypes, in, vivo])]). relacion([sujeto(['Molecular', models, of, the, 'wild-type', and, mutant, 'AreA-DNA', complexes, derived, from, the, atomic, coordinates, of, the, 'GATA-1-AGATAA', complex, account, both, for, the, phenotypes, observed, in, vivo, and, the]), verbo([binding]), complemento([differences, observed, in, vitro])]). relacion([sujeto(['Our', work, extends, the, consensus, of, physiologically, relevant]), verbo([binding]), complemento([sites, from, 'WGATAR', to, 'HGATAR,', and, provides, a, rationale, for, the, almost, universal, evolutionary, conservation, of, leucine, at, the, seventh, position, of, the, 'Zn', finger, of, 'GATA', factors])]). relacion([sujeto(['This', work, shows, inter, alia, that, the, sequence, 'CGATAGagAGATAA,', comprising, two, almost, adjacent, 'AreA-binding', 'sites,', is, sufficient, to]), verbo([ensure]), complemento([activation, of, transcription, of, the, uapA, gene])]). relacion([sujeto(['The', 'EVI-1', gene, encodes, a, 'Zn', 'finger,', 'DNA']), verbo([binding]), complemento([protein, previously, detected, in, some, acute, myelogenous, leukemias, '(', 'AML)', and, myelodysplasias, '(', 'MDS),', but, not, in, normal, marrow, or, cord, blood, cells])]). relacion([sujeto(['Experimental', studies]), verbo([suggest]), complemento(['EVI-1', blocks, cellular, differentiation, by, binding, to, 'GATA-1', or, other, specific, 'DNA', sequences, controlling, gene, 'expression,', and, may, be, involved, in, the, pathogenesis, of, some, 'AMLs'])]). relacion([sujeto(['Seven', of, 11, 'APL', cases]), verbo([expressed]), complemento(['EVI-1', 'RNA', detected, by, 'RNA', 'PCR', at, 'diagnosis,', and, expression, was, detected, in, two, additional, cases, after, treatment, with, 'all-trans', retinoic, acid, '(', 'ATRA)'])]). relacion([sujeto(['Two', of, four, cases, studied, at, relapse, also]), verbo([expressed]), complemento(['EVI-1', 'RNA'])]). relacion([sujeto(['NB4', cells, did, not]), verbo([express]), complemento(['EVI-1', under, basal, 'conditions,', but, expressed, 'EVI-1', after, 'ATRA-induced', differentiation])]). relacion([sujeto(['When', 'NB4', cells, were, exposed, to, 'ATRA', and, transferred, to, cultures, with, 'N,N\'-hexamethylene-bis-acetamide', '(', 'HMBA),', differentiation, occurred, but, 'EVI-1', 'RNA', was, not, 'detected,', indicating, that, 'EVI-1', expression, was, not]), verbo([required]), complemento([for, 'terminal,', 'NB4', differentiation])]). relacion([sujeto(['ATRA-resistant', 'NB4', cells, were, obtained, by, continuous, culture, in, gradually]), verbo([increasing]), complemento([concentrations, of, 'ATRA'])]). relacion([sujeto(['These', cells, did, not]), verbo([express]), complemento([markers, of, differentiation, but, continued, to, express, 'EVI-1', for, several, weeks, even, after, 'ATRA', withdrawal])]). relacion([sujeto(['To', assess, whether, expression, of, the, 'APL', 'PML-RAR', alpha, fusion, gene, alone, was, sufficient, for, 'ATRA', induction, of, 'EVI-1,', the, 'PML-RAR', alpha, gene, cDNA, was]), verbo([expressed]), complemento([in, 'U937', histiocytic, lymphoma, cells])]). relacion([sujeto(['ATRA', treatment, of, 'PML-RAR', 'alpha-transfected', or, control, 'U937', cells, did, not]), verbo([induce]), complemento(['EVI-1', expression])]). relacion([sujeto(['In', 'conclusion,', this, study, demonstrates, the, 'EVI-1', gene, is, consistently]), verbo([expressed]), complemento([in, 'APL', cells, either, constitutively, or, after, 'ATRA', treatment])]). relacion([sujeto(['ATRA', represents, the, first, biologically, active, agent, shown, to, specifically]), verbo([regulate]), complemento(['EVI-1', expression, in, blood, cells])]). relacion([sujeto(['In', contrast, to, previous, studies, in, 'AML', and, 'MDS,', the, pattern, of, 'EVI-1', expression]), verbo([suggests]), complemento([it, may, facilitate, rather, than, inhibit, myeloid, differentiation, during, 'ATRA', treatment])]). relacion([sujeto(['While', recent]), verbo([reports]), complemento([have, clearly, demonstrated, that, 'GATA-1', is, involved, in, the, induction, of, erythroid, 'cell-specific', forms, of, 5, -, aminolevulinate, synthase, '(', 'ALAS-2)', and, porphobilinogen, '(', 'PBG)', deaminase, and, that, cellular, iron, status, plays, a, regulatory, role, for, 'ALAS-2,', little, is, known, about, regulation, of, the, remainder, of, the, pathway])]). relacion([sujeto(['In', the, current, 'study,', we]), verbo([have]), complemento([made, use, of, a, stable, 'MEL', cell, mutant, '(', 'MEAN-1)', in, which, 'ALAS-2', enzyme, activity, is, not, induced, by, 'DMSO,', hexamethylene, bisacetamide, '(', 'HMBA),', or, butyric, acid])]). relacion([sujeto(['Addition', of, 75, microM, hemin, alone, to, the, cultures, did, not]), verbo([induce]), complemento([cells, to, terminally, differentiate, or, induce, any, of, the, pathway, enzymes])]). relacion([sujeto(['However,', the, simultaneous, addition, of, 2, '%', 'DMSO', and, 75, microM, hemin]), verbo([caused]), complemento([the, cells, to, carry, out, a, normal, program, of, terminal, erythroid, 'differentiation,', including, the, induction, of, ferrochelatase, and, 'beta-globin'])]). relacion([sujeto(['These', data]), verbo([suggest]), complemento([that, induction, of, the, entire, heme, biosynthetic, pathway, is, biphasic, in, nature, and, that, induction, of, the, terminal, enzymes, may, be, mediated, by, the, end, product, of, the, 'pathway,', heme])]). relacion([sujeto(['We']), verbo([have]), complemento([introduced, mouse, 'ALAS-2', cDNA, into, the, 'ALAS-2', mutant, cell, line, '(', 'MEAN-1)', under, the, control, of, the, mouse, metallothionein, promoter, '(', 'MEAN-RA)'])]). relacion([sujeto(['When', 'Cd', and, 'Zn', are, added, to, cultures, of, 'MEAN-RA', in, the, absence, of, 'DMSO,', 'ALAS-2', is]), verbo([induced]), complemento([but, erythroid, differentiation, does, not, occur, and, cells, continue, to, grow, normally])]). relacion([sujeto(['In', the, presence, of, metallothionein, inducers, and, 'DMSO,', the, 'MEAN-RA', cells]), verbo([induce]), complemento([in, a, fashion, similar, to, that, found, with, the, 'wild-type', 270, 'MEL', cells])]). relacion([sujeto(['In', cultures, of, 'MEAN-RA', where, 'ALAS-2', had, been]), verbo([induced]), complemento([with, 'Cd', plus, 'Zn', 24, h, prior, to, 'DMSO', 'addition,', onset, of, heme, synthesis, occurs, more, rapidly, than, when, 'DMSO', and, 'Cd', plus, 'Zn', are, added, simultaneously])]). relacion([sujeto(['This', study]), verbo([reveals]), complemento([that, induction, of, 'ALAS-2', alone, is, not, sufficient, to, induce, terminal, differentiation, of, the, 'MEAN-RA', 'cells,', and, it, does, not, appear, that, 'ALAS-2', alone, is, the, 'rate-limiting', enzyme, of, the, heme, biosynthetic, pathway, during, 'MEL', cell, differentiation])]). relacion([sujeto(['The', 'three-dimensional', solution, structure, of, a, complex, between, the, 'DNA']), verbo([binding]), complemento([domain, of, the, chicken, erythroid, transcription, factor, 'GATA-1', and, its, cognate, 'DNA', site, has, been, determined, with, multidimensional, heteronuclear, magnetic, resonance, spectroscopy])]). relacion([sujeto(['The', 'DNA']), verbo([binding]), complemento([domain, consists, of, a, core, which, contains, a, zinc, coordinated, by, four, cysteines, and, a, 'carboxyl-terminal', tail])]). relacion([sujeto(['The', core, is, composed, of, two, irregular, antiparallel, beta, sheets, and, an, alpha, 'helix,', followed, by, a, long, loop, that]), verbo([leads]), complemento([into, the, 'carboxyl-terminal', tail])]). relacion([sujeto(['The', 'amino-terminal', part, of, the, 'core,', including, the, 'helix,', is, similar, in, 'structure,', although, not, in, 'sequence,', to, the, 'amino-terminal', zinc, module, of, the, glucocorticoid, receptor, 'DNA']), verbo([binding]), complemento([domain])]). relacion([sujeto(['In', the, other, 'regions,', the, structures, of, these, two, 'DNA']), verbo([binding]), complemento([domains, are, entirely, different])]). relacion([sujeto(['The', 'DNA']), verbo([target]), complemento([site, in, contact, with, the, protein, spans, eight, base, pairs])]). relacion([sujeto(['The', helix, and, the, loop, connecting, the, two, antiparallel, beta, sheets]), verbo([interact]), complemento([with, the, major, groove, of, the, 'DNA'])]). relacion([sujeto(['The', specific, interactions, between, 'GATA-1', and, 'DNA', in, the, major, groove, are, mainly, hydrophobic, in, 'nature,', which, accounts, for, the, preponderance, of, thymines, in, the]), verbo([target]), complemento([site])]). relacion([sujeto(['Insulin-like', androgenic, gland, hormone, gene, '(', 'IAG)', is, a, sex, regulator, specifically]), verbo([expressed]), complemento([in, male, 'crustaceans,', controlling, the, male, sexual, 'differentiation,', spermatogenesis, and, reproductive, strategy])]). relacion([sujeto(['Our', previous, study]), verbo([reported]), complemento([the, cloning, and, characterization, of, the, prawn, 'Macrobrachium', nipponense, 'IAG', '(', 'MnIAG)'])]). relacion([sujeto(['In', this, 'study,', we, further, identified, a, 2214, -, bp, 'MnIAG', 5, '\'', -, flanking, 'region,', and, analyzed, its, transcription, factor]), verbo([binding]), complemento([sites, and, transcriptional, activity])]). relacion([sujeto(['The', results, showed, that, there, were, two, potential, promoter, core, 'sequences,', three, 'TATA', boxes, and, one, 'CAAT', box, existing, in, the, 'MnIAG', 5, '\'', -, flanking, region, as, well, as, many, potential, transcription, factor]), verbo([binding]), complemento(['sites,', such, as, 'SRY,', 'Sox-5,', 'GATA-1,', etc])]). relacion([sujeto(['Notably,', the, transcriptional, activity, was, weak, in, this, 'region,', and, a, negative, regulatory, region, was]), verbo([found]), complemento([in, -, 604, to, -, 231, bp])]). relacion([sujeto([nipponense, yeast, libraries, and, identified, proteins]), verbo([interacting]), complemento([with, the, 'MnIAG', protein, by, yeast, two, hybridization, assay])]). relacion([sujeto(['The', identification, of, 'MnIAG', putative, regulatory, region, and, proteins, that]), verbo([interact]), complemento([with, 'IAG', will, facilitate, our, understanding, of, the, regulatory, role, of, 'MnIAG', and, provide, a, foundation, for, deep, insight, into, the, prawn, sex, differentiation, mechanism, and, signaling, transduction, pathways])]). relacion([sujeto(['We']), verbo([have]), complemento([identified, expression, of, the, gene, encoding, the, transcriptional, coactivator, 'FOG-1', '(', 'Friend', of, 'GATA-1;', 'Zfpm1,', 'Zinc', finger, protein, multitype, 1, ')', in, 'B', lymphocytes])]). relacion([sujeto(['We']), verbo([found]), complemento([that, 'FOG-1', expression, is, directly, or, indirectly, dependent, on, the, 'B', 'cell-specific', coactivator, 'OBF-1', and, that, it, is, modulated, during, 'B', cell, 'development:', expression, is, observed, in, early, but, not, in, late, stages, of, 'B', cell, development])]). relacion([sujeto(['While', overexpression, of, 'FOG-1', in, 'B', cells, did, not, significantly, affect, 'B', cell, development, or, 'function,', we]), verbo([found]), complemento([that, enforced, expression, of, 'FOG-1', throughout, all, hematopoietic, lineages, led, to, a, reduction, in, the, number, of, circulating, 'eosinophils,', confirming, and, extending, to, mammals, the, known, function, of, 'FOG-1', in, this, lineage])]). relacion([sujeto(['The', human, 'ZNF268', gene, encodes, a, typical, 'KRAB-C2H2', zinc, finger, protein, that, may]), verbo([participate]), complemento([in, hematopoiesis, and, leukemogenesis])]). relacion([sujeto(['A', recent, microarray, study, revealed, that, 'ZNF268', expression, continuously]), verbo([decreases]), complemento([during, erythropoiesis])]). relacion([sujeto(['Here', we]), verbo([found]), complemento([that, 'GATA-1,', a, master, regulator, of, 'erythropoiesis,', repressed, the, promoter, activity, and, transcription, of, 'ZNF268'])]). relacion([sujeto(['Electrophoretic', mobility, shift, assays, and, chromatin, immunoprecipitation, assays, showed, that, 'GATA-1', directly]), verbo([bound]), complemento([to, a, 'GATA', binding, site, in, the, 'ZNF268', promoter, in, vitro, and, in, vivo])]). relacion([sujeto(['Knockdown', of, 'ZNF268', in, 'K562', erythroleukemia, cells, with, specific, siRNA, accelerated, cellular, 'proliferation,']), verbo([suppressed]), complemento(['apoptosis,', and, reduced, expression, of, 'erythroid-specific', developmental, markers])]). relacion([sujeto(['It', also]), verbo([promoted]), complemento([growth, of, subcutaneous, 'K562-derived', tumors, in, nude, mice])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, 'ZNF268', is, a, crucial, downstream, target, and, effector, of, 'GATA-1'])]). relacion([sujeto(['They', also]), verbo([suggest]), complemento([the, downregulation, of, 'ZNF268', by, 'GATA-1', is, important, in, promoting, the, growth, and, suppressing, the, differentiation, of, 'K562', erythroleukemia, cells])]). relacion([sujeto([1]), verbo([induces]), complemento([acute, leukemia, in, mice])]). relacion([sujeto(['Recent', data]), verbo([suggest]), complemento([that, the, 'leukemia-associated', fusion, protein, 'pro-myelocytic', 'leukemia/retinoic', acid, receptor, alpha, '(', 'PML/RARα)', inhibits, 'PU'])]). relacion([sujeto([1, ',', but, the, mechanism]), verbo([mediating]), complemento([this, inhibition, is, unclear])]). relacion([sujeto(['We']), verbo([found]), complemento([that, 'X-RARα', proteins, functionally, inactivate, 'PU'])]). relacion([sujeto(['In', 'fact,', 'X-RARα', proteins, directly]), verbo([interact]), complemento([with, 'PU'])]). relacion([sujeto([1, ',']), verbo([leading]), complemento([to, both, the, sequestration, of, 'PU'])]). relacion([sujeto([1, from, its]), verbo([target]), complemento([promoters, and, a, reduction, in, its, serine, 'phosphorylation,', which, is, crucial, for, its, promoter, binding, and, transcriptional, activity])]). relacion([sujeto(['We']), verbo([found]), complemento([that, the, functional, inactivation, of, 'PU'])]). relacion([sujeto([1, in, 'PML/RARα-', or, 'PLZF/RARα-positive', murine, hematopoietic, progenitor, 'cells;', 'evidently,', this, overexpression, rescued, the, leukemic, differentiation, block]), verbo([induced]), complemento([by, 'X-RARα', proteins])]). relacion([sujeto(['Our', data, thus]), verbo([provide]), complemento([strong, evidence, that, 'X-RARα', proteins, functionally, inhibit, 'PU'])]). relacion([sujeto([1, ',', shedding, light, on, the, mechanism, by, which, 'X-RARα', proteins]), verbo([induce]), complemento([leukemogenesis])]). relacion([sujeto(['The', 'LIM', only, protein, 2, '(', 'LMO2)', is, a, key, regulator, of, hematopoietic, stem, cell, development, whose, ectopic, expression, in, 'T', cells]), verbo([leads]), complemento([to, the, onset, of, acute, lymphoblastic, leukemia])]). relacion([sujeto(['Through', its, 'LIM', 'domains,', 'LMO2', is, thought, to, function, as, the, scaffold, for, a, 'DNA-binding', transcription, regulator, 'complex,', including, the, basic, 'helix-loop-helix', proteins, 'SCL/TAL1', and, 'E47,', the, zinc, finger, protein, 'GATA-1,', and, 'LIM-domain']), verbo([interacting]), complemento([protein, 'LDB1'])]). relacion([sujeto(['We', observe, a, largely, unstructured, 'LMO2', kept, in, register, by, the, 'LID']), verbo([binding]), complemento([both, 'LIM', domains])]). relacion([sujeto(['Comparison', of, independently, determined, crystal, structures, of, 'LMO2']), verbo([reveals]), complemento([large, movements, around, a, conserved, hinge, between, the, 'LIM', domains])]). relacion([sujeto(['We', demonstrate, that, such, conformational, flexibility, is, necessary, for]), verbo([binding]), complemento([of, 'LMO2', to, its, partner, protein, 'SCL/TAL1', in, vitro, and, for, the, function, of, this, complex, in, vivo])]). relacion([sujeto(['These', 'results,', together, with, molecular, docking, and, analysis, of, evolutionarily]), verbo([conserved]), complemento(['residues,', yield, the, first, structural, model, of, the, 'DNA-binding', complex, containing, 'LMO2,', 'LDB1,', 'SCL/TAL1,', and, 'GATA-1'])]). relacion([sujeto(['GATA-1,', a, zinc, 'finger-containing', transcription, 'factor,']), verbo([regulates]), complemento([not, only, the, differentiation, of, eosinophils, but, also, the, expression, of, many, 'eosinophil-specific', genes])]). relacion([sujeto(['In', the, current, 'study,', we, dissected, 'CCR3', gene, expression, at, the, molecular, level, using, several, cell, types, that]), verbo([express]), complemento([varying, levels, of, 'GATA-1', and, 'CCR3'])]). relacion([sujeto(['Chromatin', immunoprecipitation, analysis, revealed, that, 'GATA-1', preferentially]), verbo([bound]), complemento([to, sequences, in, both, exon, 1, and, its, proximal, intron, 1])]). relacion([sujeto(['A', reporter, plasmid, assay, showed, that, constructs, harboring, exon, 1, 'and/or', intron, 1, sequences]), verbo([retained]), complemento([transactivation, 'activity,', which, was, essentially, proportional, to, cellular, levels, of, endogenous, 'GATA-1'])]). relacion([sujeto(['Introduction', of, a, 'dominant-negative', 'GATA-1', or, small, interfering, 'RNA', of, 'GATA-1', resulted, in, a]), verbo([decrease]), complemento([in, transcription, activity, of, the, 'CCR3', reporter])]). relacion([sujeto(['Both', point, mutation, and, 'EMSA', analyses, demonstrated, that, although, 'GATA-1']), verbo([bound]), complemento([to, virtually, all, seven, putative, 'GATA', elements, present, in, exon, 1, -, intron, 1, ',', the, first, 'GATA', site, in, exon, 1, exhibited, the, highest, binding, affinity, for, 'GATA-1', and, was, solely, responsible, for, 'GATA-1-mediated', transactivation])]). relacion([sujeto(['Furthermore,', mutation, of, the, seventh, 'GATA', site, '(', present, in, intron, 1, ')']), verbo([increased]), complemento(['transcription,', suggesting, an, inhibitory, role])]). relacion([sujeto(['These', data]), verbo([suggest]), complemento([that, 'GATA-1', controls, 'CCR3', transcription, by, interacting, dynamically, with, the, multiple, 'GATA', sites, in, the, regulatory, region, of, the, 'CCR3', gene])]). relacion([sujeto(['Dominant', mutations, in, coding, regions, of, the, surfactant, 'protein-C', 'gene,', 'SFTPC,']), verbo([cause]), complemento([respiratory, distress, syndrome, '(', 'RDS)', in, infants])]). relacion([sujeto(['Three', promoter, 'SNPs', were, statistically]), verbo([associated]), complemento([with, neonatal, 'RDS', among, 'European', descent, infants])]). relacion([sujeto(['Each', promoter, 'SNP']), verbo([decreased]), complemento(['SFTPC', transcription])]). relacion([sujeto(['The', combination, of, two, variants, in, high, linkage, dysequilibrium, also]), verbo([decreased]), complemento(['SFTPC', transcription])]). relacion([sujeto(['In', silico, evaluation, of, transcription, factor]), verbo([binding]), complemento([demonstrated, that, the, rare, allele, at, g])]). relacion([sujeto([-, 2385, removes, a, 'MZF-1', '(', myeloid, zinc, 'finger)']), verbo([binding]), complemento(['site,', and, at, g])]). relacion([sujeto(['This', combined, 'statistical,', in, 'vitro,', and, in, silico, approach]), verbo([suggests]), complemento([that, reduced, 'SFTPC', transcription, contributes, to, the, genetic, risk, for, neonatal, 'RDS', in, developmentally, susceptible, infants])]). relacion([sujeto(['To', better, understand, 'Gfi1b', regulation, and, to, know, the, implication, of, the, level, of, expression, of, this, gene, in, human, 'pathology,', we]), verbo([have]), complemento([searched, for, promoter, punctual, sequence, variations, in, 214, patients, with, different, hematological, diseases])]). relacion([sujeto(['We']), verbo([found]), complemento([two, previously, unknown, congenital, mutations, at, evolutionary, conserved, 'GATA', and, 'octamer-binding', '(', 'Oct)', transcription, factor, sites])]). relacion([sujeto(['The', 'Oct', site, mutation, was, also]), verbo([found]), complemento([in, five, relatives, of, the, patient])]). relacion([sujeto(['The', 'GATA', motif, mutation, reduced, promoter, activity, by, 50, '%', in, 'vitro,', while, homozygous, patients, with, the, octamer, site, mutation, showed, a, 'four-to-five', times]), verbo([increase]), complemento([of, 'Gfi1b', 'RNA', in, platelets])]). relacion([sujeto(['Electrophoretic', mobility, shift, analyses, demonstrated, that, different, protein, complexes]), verbo([bind]), complemento([to, both, sites, and, that, binding, is, reduced, by, the, mutations])]). relacion([sujeto(['Finally,', we]), verbo([found]), complemento([that, 'GATA-1', and, 'Oct-1', are, the, main, components, of, each, complex])]). relacion([sujeto(['This', study]), verbo([provides]), complemento([evidences, of, a, new, mechanism, for, 'Gfi1b', repression])]). relacion([sujeto(['This', is, also, the, first]), verbo([report]), complemento([of, 'Gfi1b', mutations, with, a, functional, 'implication;', further, investigation, and, 'follow-up', will, clarify, the, involvement, of, these, mutations, in, hematological, disease])]). relacion([sujeto(['The', critical, regulator, of, hematopoiesis, 'GATA-1']), verbo([recruits]), complemento([diverse, coregulators, to, 'chromatin,', which, mediate, transcriptional, activation, and, repression])]). relacion([sujeto(['These', coregulators, include, the, 'cell-type-specific', 'multi-zinc', finger, protein, 'Friend', of, 'GATA-1', '(', 'FOG-1),', the, histone, acetyltransferase, 'CREB']), verbo([binding]), complemento([protein, '(', 'CBP),', and, the, key, component, of, the, 'Mediator', complex, 'Med1'])]). relacion([sujeto(['We', compared, the, capacity, of, 'GATA-1', to]), verbo([recruit]), complemento([and, utilize, 'FOG-1', and, 'Med1', at, activated, and, repressed, target, genes])]). relacion([sujeto(['Similar', to, 'FOG-1,', 'GATA-1']), verbo([recruited]), complemento(['Med1', to, activated, 'genes,', and, the, kinetics, of, 'FOG-1', and, 'Med1', recruitment, were, similar])]). relacion([sujeto(['GATA-1']), verbo([recruited]), complemento(['Med1', in, 'Fog1(-/-)', 'cells,', indicating, that, 'GATA-1-mediated', 'Med1', recruitment, is, 'FOG-1-independent'])]). relacion([sujeto(['However,', the, importance, of, the, 'GC-rich', region, adjacent, to, the, 3, '\'', -, end, of, this, 'GATA', site]), verbo([has]), complemento([been, also, suggested])]). relacion([sujeto(['In', this, 'study,', we, show, that, this, 'GC-rich', region, contains, five, contiguous, deoxyguanosine, residues, '(', 'G(5)', 'string)', that, are]), verbo([bound]), complemento([by, multiple, nuclear, proteins])]). relacion([sujeto(['Interestingly,', deletion, of, one, deoxyguanosine, residue, from, the, 'G(5)', string, '(', 'G(4)', 'mutant)', specifically, eliminates]), verbo([binding]), complemento([to, 'ZBP-89,', a, 'Krüppel-like', transcription, 'factor,', but, not, to, 'Sp3', and, other, binding, factors])]). relacion([sujeto(['We', demonstrate, that, 'GATA-1', and, 'ZBP-89', occupy, chromatin, regions, of, the, 'Gata1', enhancer, and, physically]), verbo([associate]), complemento([in, vitro, through, zinc, finger, domains])]). relacion([sujeto(['Gel', mobility, shift, assays, and, 'DNA', affinity, precipitation, assays]), verbo([suggest]), complemento([that, binding, of, 'ZBP-89', to, this, region, is, reduced, in, the, absence, of, 'GATA-1', binding, to, the, 'G1HE'])]). relacion([sujeto(['Luciferase', reporter, assays, demonstrate, that, 'ZBP-89']), verbo([activates]), complemento([the, 'Gata1', enhancer, depending, on, the, 'G(5)', string, sequence])]). relacion([sujeto(['Finally,', transgenic, mouse, studies]), verbo([reveal]), complemento([that, the, 'G(4)', mutation, significantly, reduced, the, reporter, activity, of, the, 'Gata1', hematopoietic, regulatory, domain, encompassing, an, 8.5, -, kbp, region, of, the, 'Gata1', gene])]). relacion([sujeto(['These', data]), verbo([provide]), complemento([compelling, evidence, that, the, 'G(5)', string, is, necessary, for, 'Gata1', gene, expression, in, vivo, and, 'ZBP-89', is, the, functional, 'trans-acting', factor, for, this, 'cis-acting', region])]). relacion([sujeto(['The', stages, of, mammalian, erythropoiesis, include, global, gene, 'inactivation,']), verbo([nuclear]), complemento(['condensation,', and, enucleation, to, yield, circulating, 'erythrocytes,', and, some, of, the, genes, whose, expression, are, altered, by, 'GATA-1', during, this, process, are, members, of, the, p53, pathway])]). relacion([sujeto(['We', also, show, by, immunoprecipitation, that, the, native, 'GATA-1', and, p53]), verbo([interact]), complemento([in, erythroid, cells, and, that, activation, of, 'p53-responsive', promoters, in, an, erythroid, cell, line, can, be, inhibited, by, the, overexpression, of, 'GATA-1'])]). relacion([sujeto(['Mutational', analysis]), verbo([reveals]), complemento([that, 'GATA-1', inhibition, of, p53, minimally, requires, the, segment, of, the, 'GATA-1', 'DNA-binding', domain, that, interacts, with, p53TAD])]). relacion([sujeto(['This', inhibition, is, 'reciprocal,', as, the, activation, of, a, 'GATA-1-responsive', promoter, can, be]), verbo([inhibited]), complemento([by, p53])]). relacion([sujeto(['The', med, genes, are, transcriptional, regulators, that, are]), verbo([involved]), complemento([in, the, specification, of, the, mesoderm, and, endoderm, precursor, cells, in, nematodes])]). relacion([sujeto(['Unlike', other, 'GATA-type', zinc, fingers, that]), verbo([recognize]), complemento([the, consensus, sequence, '(', 'A/C/T)GATA(A/G),', the, 'MED-1', zinc, finger, '(', 'MED1zf)', binds, the, larger, and, atypical, site, 'GTATACT(T/C)(3)'])]). relacion([sujeto(['We']), verbo([have]), complemento([examined, the, basis, for, this, unusual, 'DNA', specificity, using, a, range, of, biochemical, and, biophysical, approaches])]). relacion([sujeto(['Most', 'strikingly,', we, show, that, although, the, core, of, the, 'MED1zf', structure, is, similar, to, that, of, 'GATA-1,', the, basic, tail, 'C-terminal', to, the, zinc, finger, unexpectedly, adopts, an, 'alpha-helical', structure, upon]), verbo([binding]), complemento(['DNA'])]). relacion([sujeto(['The', promoter, region, contained, many, putative, transcription, factor]), verbo([binding]), complemento([sites, such, as, 'c-Myb,', 'Oct-1,', 'Sp1,', 'Kruppel-like,', 'c-ETS,', 'NFkappaB,', 'GATA-1,', 'AP-1,', and, 'Ubx', binding, sites])]). relacion([sujeto(['Although', a, high, expression, level, of, 'ZNF521', in, human, 'CD34+', progenitors, and, hematopoietic, malignancies]), verbo([has]), complemento([been, 'demonstrated,', the, functional, role, of, 'ZNF521', in, hematopoietic, cell, differentiation, has, not, been, clarified])]). relacion([sujeto(['Down-regulation', of, 'ZNF521']), verbo([mediated]), complemento([by, transient, expression, of, shRNA, for, 'ZNF521', resulted, in, increased, synthesis, of, hemoglobin, in, 'K562', and, 'HEL', cell, lines, as, compared, with, control, cells])]). relacion([sujeto(['K562-derived', clones, in, which, 'ZNF521', was, constitutively, silenced, by, shRNA, also, showed, marked, synthesis, of, hemoglobin, and, an]), verbo([increased]), complemento([expression, level, of, glycophorin, 'A'])]). relacion([sujeto(['GATA-1', activity, was, markedly]), verbo([inhibited]), complemento([by, 'ZNF521', in, a, 'dose-dependent', manner])]). relacion([sujeto(['Deletion', analysis, of, 'ZNF521', showed, that, the, repressive, effect]), verbo([requires]), complemento([an, 'N-terminal', repression, motif])]). relacion([sujeto(['These', results, indicate, that, 'ZNF521']), verbo([modulates]), complemento([erythroid, cell, differentiation, through, direct, binding, with, 'GATA-1'])]). relacion([sujeto(['The', 'alpha-chain', is, a, specific, component, of, 'FcepsilonRI,', which, is, essential, for, the, cell, surface, expression, of, 'FcepsilonRI', and, the]), verbo([binding]), complemento([of, 'IgE'])]). relacion([sujeto(['Recently,', two, single, nucleotide, polymorphisms, '(', 'SNPs)', in, the, 'alpha-chain', 'promoter,', -, 315, 'C>T', and, -, 66, 'T>C,']), verbo([have]), complemento([been, shown, by, statistic, studies, to, associate, with, allergic, diseases])]). relacion([sujeto(['The', effect, of, -, 66, 'SNP', on, 'GATA-1-mediated', promoter, activity]), verbo([has]), complemento([been, already, indicated])]). relacion([sujeto(['EMSA', indicated, that, the, transcription, factor, 'Sp1,', but, not, 'Myc-associated', zinc, finger, protein, '(', 'MAZ),', was]), verbo([bound]), complemento([to, the, -, 315, 'C', allele, probe, and, that, a, transcription, factor, belonging, to, a, high, mobility, 'group-family', bound, to, the, -, 315, 'T', allele, probe])]). relacion([sujeto(['The', chromatin, immunoprecipitation, assay]), verbo([suggested]), complemento([that, high, mobility, group, 1, ',', 2, ',', and, 'Sp1', bound, around, -, 315, of, 'FcepsilonRIalpha', genomic, 'DNA', in, vivo, in, the, human, basophil, cell, line, 'KU812', with, -, 315, 'C/T', and, in, human, peripheral, blood, basophils, with, -, 315, 'C/C,', respectively])]). relacion([sujeto(['When', cell, surface, expression, level, of, 'FcepsilonRI', on, basophils, was, analyzed, by, flow, 'cytometry,', basophils, from, individuals, carrying, -, 315, 'T', allele]), verbo([expressed]), complemento([significantly, higher, amount, of, 'FcepsilonRI', compared, with, those, of, -, 315, 'C/C'])]). relacion([sujeto(['The', findings, demonstrate, that, a, -, 315, 'SNP', significantly, affects, human, 'FcepsilonRI', 'alpha-chain', promoter, activity, and, expression, level, of, 'FcepsilonRI', on, basophils, by]), verbo([binding]), complemento([different, transcription, factors, to, the, 'SNP', site])]). relacion([sujeto(['The', common, thread, among, these, diverse, structures, is, their, 'sequence-specific']), verbo([binding]), complemento([to, essential, promoter, or, other, genetic, regulatory, sequences, with, high, selectivity, and, affinity])]). relacion([sujeto(['This', family, of, 'DNA-binding', proteins, is, characterized, by, the, presence, of, one, or, two, '(', 'Cys)(4)', metal]), verbo([binding]), complemento([sites, which, recognize, the, 'protein\'s', eponymous, binding, 'site,', 'GATA'])]). relacion([sujeto(['Unlike', other]), verbo([conserved]), complemento(['DNA-binding', 'domains,', 'Gata', proteins, appear, to, be, restricted, to, binding, consensus, 'GATA', 'sequences,', or, near, 'variations,', in, 'DNA'])]). relacion([sujeto(['Since', the, architecture, of, the, 'Gata', finger, seems, built, around]), verbo([recognizing]), complemento([this, particular, 'sequence,', we, set, out, to, define, the, allowable, range, of, amino, acid, substitutions, along, the, 'DNA-binding', surface, of, a, 'Gata', finger, that, could, continue, to, support, 'sequence-specific', 'DNA-binding', activity])]). relacion([sujeto(['Mutant', libraries, were, generated, at, five, amino, acids, identified, in, the, 'Gata-DNA', structure, as, likely, to]), verbo([mediate]), complemento(['sequence-specific', contacts, between, the, 'Gata', finger, and, 'DNA'])]). relacion([sujeto(['Screening', and, characterization, of, these, libraries, revealed, several, functional, amino, acid, substitutions, at, two, leucines, which, contact, the, 'DNA', at, the, 3, '\'', and, 5, '\'', flanks, of, the, 'GATA']), verbo([binding]), complemento(['site,', but, no, functional, substituents, for, amino, acids, near, the, core, of, the, binding, site])]). relacion([sujeto(['Classical', zinc, fingers, '(', 'ZFs)', are, traditionally, considered, to]), verbo([act]), complemento([as, 'sequence-specific', 'DNA-binding', domains])]). relacion([sujeto(['More', 'recently,', classical, 'ZFs']), verbo([have]), complemento([been, recognised, as, potential, 'RNA-binding', 'modules,', raising, the, intriguing, possibility, that, 'classical-ZF', transcription, factors, are, involved, in, 'post-transcriptional', gene, regulation, via, direct, 'RNA', binding])]). relacion([sujeto(['To', 'date,', 'however,', only, one, classical, 'ZF-RNA', 'complex,', that]), verbo([involving]), complemento(['TFIIIA,', has, been, structurally, characterised])]). relacion([sujeto(['Yin', 'Yang-1', '(', 'YY1)', is, a, 'multi-functional', transcription, factor]), verbo([involved]), complemento([in, many, regulatory, 'processes,', and, binds, 'DNA', via, four, classical, 'ZFs'])]). relacion([sujeto(['Recent', evidence]), verbo([suggests]), complemento([that, 'YY1', also, interacts, with, 'RNA,', but, the, molecular, nature, of, the, interaction, remains, unknown])]). relacion([sujeto(['In', the, present, 'work,', we, directly, assess, the, ability, of, 'YY1', to]), verbo([bind]), complemento(['RNA', using, in, vitro, assays])]). relacion([sujeto(['Systematic', 'Evolution', of, 'Ligands', by, 'EXponential', enrichment, '(', 'SELEX)', was, used, to, identify, preferred, 'RNA', sequences]), verbo([bound]), complemento([by, the, 'YY1', 'ZFs', from, a, randomised, library, over, multiple, rounds, of, selection])]). relacion([sujeto(['However,', a, strong, motif, was, not, consistently, 'recovered,']), verbo([suggesting]), complemento([that, the, 'RNA', sequence, selectivity, of, these, domains, is, modest])]). relacion([sujeto(['YY1', 'ZF', residues]), verbo([involved]), complemento([in, binding, to, 'single-stranded', 'RNA', were, identified, by, 'NMR', spectroscopy, and, found, to, be, largely, distinct, from, the, set, of, residues, involved, in, 'DNA', 'binding,', suggesting, that, interactions, between, 'YY1', and, ssRNA, constitute, a, separate, mode, of, nucleic, acid, binding])]). relacion([sujeto(['Our', data, are, consistent, with, recent]), verbo([reports]), complemento([that, 'YY1', can, bind, to, 'RNA', in, a, 'low-specificity,', yet, physiologically, relevant, manner])]). relacion([sujeto(['Functional', silencers, are, also]), verbo([found]), complemento([at, similar, locations, within, three, other, animal, mariner, 'elements,', i])]). relacion([sujeto(['We']), verbo([report]), complemento([that, the, silencing, involves, at, least, two, transcription, factors, '(', 'TFs)', that, are, conserved, within, animal, 'species,', 'NFAT-5', and, 'Alx1'])]). relacion([sujeto(['These', cooperatively]), verbo([act]), complemento([with, 'YY1', to, trigger, the, silencing, activity])]). relacion([sujeto(['Four', other, housekeeping, transcription, factors, '(', 'TFs),', neuron, restrictive, silencer, factor, '(', 'NRSF),', 'GAGA', factor, '(', 'GAF)', and, 'GTGT', factor, '(', 'GTF),', were, also]), verbo([found]), complemento([to, have, binding, sites, within, mariner, silencers, but, their, impact, in, modulating, the, silencer, activity, remains, to, be, further, specified])]). relacion([sujeto(['Interestingly,', an, 'NRSF']), verbo([binding]), complemento([site, was, found, to, overlap, a, 30, bp, motif, coding, a, highly, conserved, 'PHxxYSPDLAPxD', peptide, in, mariner, transposases])]). relacion([sujeto(['However,', we, observe, that, when, 'PRC2', is, impaired, another, host, silencing, pathway, potentially, takes, over, to]), verbo([maintain]), complemento([weak, silencer, activity])]). relacion([sujeto(['Mariner', silencers, harbour, features, of, 'Polycomb', 'Response', 'Elements,', which, are, probably, a, way, for, mariner, elements, to, 'self-repress', their, transcription, and, mobility, in, somatic, and, germinal, cells, when, the]), verbo([required]), complemento(['TFs', are, expressed])]). relacion([sujeto(['At', the, evolutionary, 'scale,', mariner, 'elements,', through, their, 'exaptation,', might]), verbo([have]), complemento([been, a, source, of, silencers, playing, a, role, in, the, chromatin, configuration, in, eukaryotic, genomes])]). relacion([sujeto(['There', is, an, urgent, need, to, investigate, the, potential]), verbo([targeted]), complemento([therapy, approach, for, 'triple-negative', breast, cancer, '(', 'TNBC)'])]). relacion([sujeto(['Our', present, study]), verbo([reveals]), complemento([that, histone, deacetylase, inhibitors, '(', 'HDACIs)', suberoyl, anilide, hydroxamic, acid, '(', 'SAHA)', and, sodium, butyrate, '(', 'NaB)', significantly, inhibit, cell, 'proliferation,', arrest, cell, cycle, at, 'G0/G1', 'phase,', and, induce, mitochondrial, related, apoptosis, of, 'TNBC', cells])]). relacion([sujeto(['Further,', 'SAHA', and, 'NaB']), verbo([decrease]), complemento([the, 'phosphorylation,', protein, and, mRNA, levels, of, mutant, p53, '(', 'mtp53)', in, 'TNBC', cells])]). relacion([sujeto(['While', 'SAHA', or, 'NaB']), verbo([has]), complemento([no, similar, inhibition, effect, on, wild, type, p53, '(', 'wtp53)'])]). relacion([sujeto(['The', knockdown, of, 'HDAC8,', while, not, 'HDAC6,']), verbo([inhibits]), complemento([the, transcription, of, mtp53, in, 'TNBC', cells])]). relacion([sujeto(['The', luciferase, assay, and, 'ChIP', analysis]), verbo([reveal]), complemento([that, both, 'SAHA', and, 'NaB', can, reduce, the, binding, of, transcription, factor, 'Yin', 'Yang', 1, '(', 'YY1)', with, the, -, 102, to, -, 96, position, of, human, p53, promoter])]). relacion([sujeto(['Knockdown', of, 'YY1', also, significantly]), verbo([inhibits]), complemento([the, transcription, of, mtp53, in, 'TNBC', cells])]). relacion([sujeto(['Further,', 'SAHA', and, 'NaB', can]), verbo([inhibit]), complemento([the, association, of, 'HDAC8', and, 'YY1,', increase, acetylation, of, residues, 170, -, 200, of, 'YY1,', then, decrease, its, transcription, 'activities,', and, finally, suppress, 'YY1', induced, p53, transcription])]). relacion([sujeto(['Together,', our, data, establish, that, 'SAHA', and, 'NaB', can, be, considered, as, drug, candidates, for, 'TNBC', 'patients,', and, 'HDAC8/YY1/mtp53', signals]), verbo([act]), complemento([as, an, important, target, for, 'TNBC', treatment])]). relacion([sujeto(['Proline/arginine-rich', end, 'leucine-rich', repeat, protein, '(', 'PRELP)', is, a, 'collagen-binding', proteoglycan, highly]), verbo([expressed]), complemento([in, the, developing, bones])]). relacion([sujeto(['Recent', studies, indicated, that, 'PRELP', could]), verbo([inhibit]), complemento([osteoclastogenesis, as, a, 'NF-κB', inhibitor])]). relacion([sujeto(['In', this, 'study,', we, confirmed, that, the, expression, of, 'PRELP']), verbo([increased]), complemento([with, the, osteogenesis, induction, of, preosteoblastic, 'MC3T3-E1', cells])]). relacion([sujeto(['Our', microarray, analysis, data]), verbo([suggested]), complemento([that, 'β-catenin', may, act, as, a, hub, gene, in, the, 'PRELP-mediated', gene, network])]). relacion([sujeto(['We', validated, furtherly, that, 'PRELP', knockdown, could]), verbo([inhibit]), complemento([the, level, of, 'connexin43,', a, key, regulator, of, osteoblast, differentiation, by, affecting, 'β-catenin', protein, 'expression,', and, its, nuclear, translocation, in, 'MC3T3-E1', preosteoblasts])]). relacion([sujeto(['Therefore,', this, study, established, a, new, role, of, 'PRELP', in]), verbo([modulating]), complemento(['β-catenin/connexin43', pathway, and, osteoblast, differentiation])]). relacion([sujeto(['In', this, 'study,', the, opioid, antagonist, 'β-funaltrexamine', '(', 'β-FNA)']), verbo([decreases]), complemento([the, expression, and, release, of, an, inflammatory, 'chemokine,', 'interferon-γ', inducible, 'protein-10', '(', 'CXCL10)', from, normal, human, astrocytes, stimulated, by, interleukin, 1, β, '(', 'IL-1β)'])]). relacion([sujeto(['β-FNA']), verbo([decreased]), complemento(['CXCL10', by, an, unknown, action, that, did, not, involve, the, mu, opioid, receptor, '(', 'MOR)'])]). relacion([sujeto(['As', 'IL-1β']), verbo([acts]), complemento([through, its, receptor, to, activate, 'NF-κB/MAPK', signaling, pathways, which, leads, to, 'CXCL10', expression, and, 'release,', key, steps, in, the, 'IL-1β', signaling, pathways, were, examined, following, 'β-FNA', treatment])]). relacion([sujeto(['IL-1β-induced', activation, of, p38, 'mitogen-activated', protein, kinases, '(', p38, 'MAPK)', was]), verbo([inhibited]), complemento([by, 'β-FNA', as, shown, by, decreased, p38, 'MAPK', phosphorylation, in, treated, cells])]). relacion([sujeto(['β-FNA', also]), verbo([decreased]), complemento([the, levels, of, activated, subunits, of, 'NF-κB', '(', p50, and, 'p65)', in, treated, astrocytes])]). relacion([sujeto(['The', impact, of, 'β-FNA', was, also, observed, in, proteins, that]), verbo([act]), complemento([to, negatively, regulate, 'NF-κB', signaling])]). relacion([sujeto(['IL-1β', upregulated, the, expression, of, 'A20,', a, ubiquitin, '(', 'Ub)-editing', enzyme, that, dampens, 'NF-κB', signaling, by, altering, ubiquination, patterns, on, 'IL-1', receptor, second, 'messengers,', and, the]), verbo([increase]), complemento([in, 'A20', was, significantly, inhibited, by, 'β-FNA', treatment])]). relacion([sujeto(['Inhibition', of, the, 'Ub-activating', enzyme, 'E1', by, the, inhibitor, 'PYR41', also]), verbo([decreased]), complemento(['CXCL10', 'release,', like, 'β-FNA,', and, concurrent, treatment, with, both, 'PYR41', and, 'β-FNA', inhibited, 'CXCL10', more, than, did, either, agent, alone])]). relacion([sujeto(['In', 'mice,', 'lipopolysaccharide-induced', 'CXCL10', expression, in, the, brain, was]), verbo([inhibited]), complemento([by, treatment, with, 'β-FNA'])]). relacion([sujeto(['These', findings]), verbo([suggest]), complemento([that, 'β-FNA', exerts, an, 'anti-inflammatory', action, in, vitro, and, in, vivo, that, is, 'MOR-independent', and, possibly, due, to, the, alkylating, ability, of, 'β-FNA'])]). relacion([sujeto(['Here,', we, use, a, 'Systems', 'Biology', '(', 'SB)', 'approach,', which]), verbo([has]), complemento([been, highly, successful, in, the, dissection, of, cancer, related, 'phenotypes,', to, reverse, engineer, the, transcriptional, regulation, layer, of, human, neuronal, cells, and, interrogate, it, to, infer, candidate, 'Master', 'Regulators', '(', 'MRs)', responsible, for, disease, progression])]). relacion([sujeto(['Interrogation', of, this, 'interactome,', using, the, 'Master', 'Regulator', 'INference', algorithm, '(', 'MARINa),', identified, an, unbiased, set, of, candidate, 'MRs', causally, responsible, for]), verbo([regulating]), complemento([the, transcriptional, signature, of, 'AD', progression])]). relacion([sujeto(['Our', results, additionally, implicate, p53, and]), verbo([loss]), complemento([of, acetylation, homeostasis, in, the, neurodegenerative, process])]). relacion([sujeto(['This', study]), verbo([suggests]), complemento([that, an, 'integrative,', 'SB', approach, can, be, applied, to, 'AD', and, other, neurodegenerative, 'diseases,', and, provide, significant, novel, insight, on, the, disease, progression])]). relacion([sujeto(['Astrocytes', play, a, key, role, in, maintenance, of, neuronal, functions, in, the, central, nervous, system, by, producing, various, 'cytokines,', 'chemokines,', and, growth, 'factors,', which]), verbo([act]), complemento([as, a, molecular, coordinator, of, 'neuron-glia', communication])]). relacion([sujeto(['Non-stimulated', human, astrocytes, in, culture]), verbo([expressed]), complemento([eight, 'cytokines,', including, 'G-CSF,', 'GM-CSF,', 'GROα', '(', 'CXCL1),', 'IL-6,', 'IL-8', '(', 'CXCL8),', 'MCP-1', '(', 'CCL2),', 'MIF', and, 'Serpin', 'E1'])]). relacion([sujeto(['Following', stimulation, with, 'IL-1β', and, 'TNF-α,']), verbo([activated]), complemento([astrocytes, newly, produced, 'IL-1β,', 'IL-1ra,', 'TNF-α,', 'IP-10', '(', 'CXCL10),', 'MIP-1α', '(', 'CCL3)', and, 'RANTES', '(', 'CCL5),', in, addition, to, the, induction, of, 'sICAM-1', and, complement, component, 5])]). relacion([sujeto(['Database', search, indicated, that, most, of, cytokines, and, chemokines, produced, by, 'non-stimulated', and]), verbo([activated]), complemento([astrocytes, are, direct, targets, of, the, transcription, factor, 'NF-kB'])]). relacion([sujeto(['These', results, indicated, that, cultured, human, astrocytes]), verbo([express]), complemento([a, distinct, set, of, 'NF-kB-target', cytokines, and, chemokines, in, resting, and, activated, 'conditions,', suggesting, that, the, 'NF-kB', signaling, pathway, differentially, regulates, gene, expression, of, cytokines, and, chemokines, in, human, astrocytes, under, physiological, and, inflammatory, conditions])]). relacion([sujeto(['Matrix', 'metalloproteinase-9', '(', 'MMP-9)']), verbo([has]), complemento([been, shown, to, be, induced, by, cytokines, including, 'TNF-α', and, may, contribute, to, bone, inflammatory, diseases])]). relacion([sujeto(['However,', the, mechanisms, underlying, 'MMP-9', expression]), verbo([induced]), complemento([by, 'TNF-α', in, 'MC3T3-E1', cells, remain, unclear])]). relacion([sujeto(['D),', translation, '(', 'cycloheximide,', 'CHI),', 'c-Src', '(', 'PP1),', 'MEK1/2', '(', 'U0126),', p38, 'MAPK', '(', 'SB202190),', 'JNK1/2', '(', 'SP600125),', and, 'NF-κB', '(', 'Bay11-7082),', respective, siRNAs, 'transfection,', promoter, 'assay,', immunofluorescence, 'staining,', and, 'ELISA', to, investigate, the, 'MMP-9', expression, and, soluble, 'ICAM-1', '(', 'sICAM-1)']), verbo([release]), complemento([induced, by, 'TNF-α', in, 'MC3T3-E1', cells])]). relacion([sujeto(['TNF-α', 'time-dependently']), verbo([induced]), complemento(['MMP-9', promoter, activity, which, was, also, inhibited, by, 'PP1,', 'U0126,', 'SB202190,', 'SP600125,', or, 'Bay11-7082'])]). relacion([sujeto(['Up-regulation', of, 'MMP-9', was]), verbo([associated]), complemento([with, the, release, of, 'sICAM-1', into, the, cultured, 'medium,', which, was, attenuated, by, the, pretreatment, with, 'MMP-2/9i,', an, 'MMP-9', inhibitor])]). relacion([sujeto(['The', interplay, between, 'MMP-9', expression, and, 'sICAM-1']), verbo([release]), complemento([may, exert, an, important, role, in, the, regulation, of, bone, inflammatory, diseases])]). relacion([sujeto(['TGF-β', evokes, cellular, responses, by, signaling, mainly, through, cell, membrane, receptors, and, transcription, factor, 'R-Smads', and, 'Co-Smad', '(', 'Smad4),', while, an, inhibitory, 'Smad,', 'Smad7,']), verbo([acts]), complemento([as, a, critical, negative, regulator, of, 'TGF-β', signaling])]). relacion([sujeto(['Smad7', antagonizes, 'TGF-β', signaling, by]), verbo([regulating]), complemento([the, stability, or, activity, of, the, receptors, or, blocking, the, 'DNA', binding, of, the, functional, 'R-Smad-Smad4', complex, in, the, nucleus])]). relacion([sujeto(['Yin', 'Yang', 1, '(', 'YY1)', is, a, ubiquitously]), verbo([expressed]), complemento([transcription, factor, with, multiple, functions])]). relacion([sujeto(['It']), verbo([has]), complemento([been, reported, that, 'YY1', can, inhibit, 'Smad-dependent', transcriptional, responses, and, 'TGF-β/BMP-induced', cell, differentiation, independently, of, its, 'DNA', binding, ability])]). relacion([sujeto(['In', this, 'study,', we]), verbo([found]), complemento([that, 'Smad7', interacts, with, 'YY1', and, the, interaction, is, attenuated, by, 'TGF-β', signaling])]). relacion([sujeto(['Reporter', assays, and]), verbo([target]), complemento([gene, expression, analyses, revealed, that, 'Smad7', and, 'YY1', act, in, concert, to, inhibit, 'TGF-β-induced', transcription, in, the, nucleus])]). relacion([sujeto(['Furthermore,', 'Smad7', could]), verbo([enhance]), complemento([the, interaction, of, 'YY1', with, the, histone, deacetylase, 'HDAC1'])]). relacion([sujeto(['Trim28,', a, key, player, in, this, 'silencing,', is, known, to]), verbo([act]), complemento([in, a, large, 'DNA-bound', 'complex,', but, the, other, components, of, the, complex, are, not, fully, characterized])]). relacion([sujeto(['YY1']), verbo([binds]), complemento([to, the, long, terminal, repeat, '(', 'LTR)', region, of, both, exogenous, and, endogenous, retroviruses, '(', 'ERVs)'])]). relacion([sujeto(['Deletion', of, the, 'YY1-binding', site, from, the, retroviral, genome]), verbo([leads]), complemento([to, a, major, loss, of, silencing, in, embryonic, cells, and, a, coordinated, loss, of, repressive, histone, marks, from, the, proviral, chromatin])]). relacion([sujeto(['Finally,', we]), verbo([report]), complemento([an, embryonic, 'cell-specific', interaction, between, 'YY1', and, 'Trim28'])]). relacion([sujeto(['Our', results]), verbo([suggest]), complemento([a, major, role, for, 'YY1', in, the, silencing, of, both, exogenous, retroviruses, and, 'ERVs', in, embryonic, cells])]). relacion([sujeto(['The', 'genome-wide', mapping, of, the, major, gene, expression, 'regulators,', the, transcription, factors, '(', 'TFs)', and, their, 'DNA']), verbo([binding]), complemento(['sites,', is, of, great, importance, for, describing, cellular, behavior, and, phenotypic, diversity])]). relacion([sujeto(['Presently,', the, methods, for, prediction, of, genomic, 'TF']), verbo([binding]), complemento([produce, a, large, number, of, false, 'positives,', most, likely, due, to, insufficient, description, of, the, physiochemical, mechanisms, of, 'protein-DNA', binding])]). relacion([sujeto(['Growing', evidence]), verbo([suggests]), complemento(['that,', in, the, 'cell,', the, 'double-stranded', 'DNA', '(', 'dsDNA)', is, subject, to, local, transient, strands, separations, '(', 'breathing)', that, contribute, to, genomic, functions])]). relacion([sujeto(['By', using, 'site-specific', chromatin, 'immunopecipitations,', gel, 'shifts,', 'BIOBASE', 'data,', and, our, model, that, accurately, describes, the, melting, behavior, and, breathing, dynamics, of, dsDNA, we]), verbo([report]), complemento([a, specific, 'DNA', breathing, profile, found, at, 'YY1', binding, sites, in, cells])]). relacion([sujeto(['We']), verbo([find]), complemento([that, the, genomic, flanking, sequence, variations, and, 'SNPs,', may, exert, 'long-range', effects, on, 'DNA', dynamics, and, predetermine, 'YY1', binding])]). relacion([sujeto(['The', ubiquitous, 'TF', 'YY1']), verbo([has]), complemento([a, fundamental, role, in, essential, biological, processes, by, 'activating,', initiating, or, repressing, transcription, depending, upon, the, sequence, context, it, binds])]). relacion([sujeto(['We', anticipate, that, consensus]), verbo([binding]), complemento([sequences, together, with, the, related, 'DNA', dynamics, profile, may, significantly, improve, the, accuracy, of, genomic, 'TF', binding, sites, and, 'TF', 'binding-related', functional, 'SNPs'])]). relacion([sujeto(['Rex1']), verbo([regulates]), complemento(['muERV-L', expression, in, 'vivo,', as, we, show, altered, levels, upon, transient, 'gain-and-loss', of, 'Rex1', function, in, 'pre-implantation', embryos])]). relacion([sujeto(['We', also]), verbo([find]), complemento(['REX1', can, associate, with, the, 'lysine-demethylase', 'LSD1/KDM1A,', suggesting, they, act, in, concert])]). relacion([sujeto(['Similar', to, 'REX1']), verbo([binding]), complemento([to, retrotransposable, elements, '(', 'REs)', in, 'ES', 'cells,', we, also, detected, binding, of, the, 'REX1', related, proteins, 'YY1', and, 'YY2', to, 'REs,', although, the, binding, preferences, of, the, two, proteins, were, slightly, different])]). relacion([sujeto(['Altogether,', we, show, that, 'Rex1']), verbo([regulates]), complemento(['ERV', expression, in, mouse, 'ES', cells, and, during, 'pre-implantation', development, and, suggest, that, 'Rex1', and, its, relatives, have, evolved, as, regulators, of, endogenous, retroviral, transcription])]). relacion([sujeto(['AMP-activated', protein, kinase, '(', 'AMPK)', is, currently, known, to]), verbo([act]), complemento([as, a, key, regulator, of, metabolic, homeostasis])]). relacion([sujeto(['Several', biosynthetic, enzymes, for, fatty, acid, or, glycogen, are]), verbo([recognized]), complemento([as, the, targets, of, 'AMPK'])]). relacion([sujeto(['IL-1']), verbo([induced]), complemento([phosphorylation, of, 'AMPK-α', '(', 'Thr-172),', which, regulates, 'AMPK', 'activities,', and, 'acetyl-CoA', 'carboxylase,', a, direct, substrate, of, 'AMPK'])]). relacion([sujeto(['Compound', 'C,', an, inhibitor, of, 'AMPK,', which]), verbo([suppressed]), complemento([the, 'IL-1-induced', phosphorylation, of, 'acetyl-CoA', 'carboxylase,', increased, the, release, and, the, mRNA, level, of, 'IL-6', stimulated, by, 'IL-1'])]). relacion([sujeto(['Transfection', of, 'AMPK', 'siRNA-α', also, amplified, the, 'IL-1-stimulated', 'IL-6']), verbo([release]), complemento([compared, to, the, control, cells])]). relacion([sujeto(['On', the, other, 'hand,', 'IL-1', elicited, the, phosphorylation, of, 'IκB,', which]), verbo([caused]), complemento([subsequent, decrease, of, total, level, of, 'IκB'])]). relacion([sujeto(['Wedelolactone,', an, inhibitor, of, 'IκB', 'kinase,', which, reduced, the, phosphorylation, both, of, 'IκB', and, 'NF-κB,', significantly]), verbo([enhanced]), complemento([the, 'IL-1-stimulated', 'IL-6', synthesis])]). relacion([sujeto(['Compound', 'C', remarkably]), verbo([suppressed]), complemento([the, 'IL-1-induced', phosphorylation, of, 'IκB'])]). relacion([sujeto(['These', results, strongly]), verbo([suggest]), complemento([that, 'AMPK', negatively, regulates, 'IL-1-stimulated', 'IL-6', synthesis, through, the, 'IκB/NF-κB', pathway, in, osteoblasts])]). relacion([sujeto(['Methoxyphenolic', compounds, are, purported, to, be, effective, 'anti-inflammatory', 'agents,', but, their, effects, on, the, airway, epithelium]), verbo([have]), complemento([not, been, well, characterized])]). relacion([sujeto(['Human', airway, cells, were]), verbo([stimulated]), complemento([with, 'TNF-α', in, the, presence, or, absence, of, 4, -, substituted, methoxyphenols, and, resveratrol])]). relacion([sujeto(['Activation', of, 'NF-κB', was, measured, by]), verbo([nuclear]), complemento([translocation, and, phosphorylation])]). relacion([sujeto(['Multiple', inflammatory, mediators, were]), verbo([inhibited]), complemento([by, 'methoxyphenols,', 'including:', 'CCL2,', 'CCL5,', 'IL-6,', 'IL-8,', 'ICAM-1,', 'MIF,', 'CXCL1,', 'CXCL10,', and, 'Serpin', 'E1'])]). relacion([sujeto(['However,', methoxyphenols]), verbo([inhibited]), complemento([binding, of, the, 'RNA-binding', protein, 'HuR', to, 'mRNA,', indicating, that, they, may, act, 'post-transcriptionally'])]). relacion([sujeto(['More', potent, compounds, that]), verbo([act]), complemento([via, similar, mechanisms, may, have, therapeutic, potential, as, novel, 'anti-inflammatory', agents])]). relacion([sujeto(['These', are, key, to, cancer, 'development,', as, a, consequence, of, which, its, expression]), verbo([has]), complemento([been, studied, in, an, increasingly, wide, range, of, human, 'cancers,', including, 'lymphoma,', 'breast,', 'prostate,', 'colon,', 'ovarian,', 'cervical,', and, brain, 'cancers,', 'osteosarcoma,', 'rhabdomyosarcoma,', and, leukemia])]). relacion([sujeto(['It', is, a, regulatory, transcription, factor, for, a, wide, range, of, 'genes,', including, genes]), verbo([involved]), complemento([in, control, of, the, cell, cycle, and, 'apoptosis,', and, it, can, act, either, to, upregulate, or, downregulate, downstream, gene, 'expression,', depending, on, the, cellular, 'environment,', 'cofactors,', and, the, gene, targeted])]). relacion([sujeto(['Its', expression]), verbo([has]), complemento([been, associated, with, development, of, a, malignant, phenotype, in, some, human, 'cancers;', tumor, 'progression,', including, 'metastasis;', and, survival])]). relacion([sujeto(['However,', as, data, on, its, prognostic, significance]), verbo([has]), complemento([become, available, for, more, human, 'cancers,', its, role, in, tumor, progression, has, become, 'controversial;', there, is, conflicting, data, on, its, association, with, 'outcome,', with, some, studies, showing, a, favorable, and, others, an, unfavorable, association])]). relacion([sujeto(['These', studies, are, reviewed, to, give, an, overview, of, the, increasingly]), verbo([recognized]), complemento([importance, of, 'YY1', in, human, tumorigenesis])]). relacion([sujeto(['YY1', is, a, ubiquitous, and, multifunctional, 'zinc-finger', transcription, factor, member, of, the, 'Polycomb', group, protein, 'family,', a, group, of, homeobox, gene, receptors, that, can]), verbo([act]), complemento([as, activators, or, repressors, of, transcriptional, activity])]). relacion([sujeto(['Furthermore,', 'YY1', can]), verbo([act]), complemento([as, a, redox, 'sensor,', adaptor, 'molecule,', and, chromatin, structure, and, function, regulator])]). relacion([sujeto(['YY1', also]), verbo([has]), complemento([been, shown, to, undergo, chromatin, remodeling, via, interactions, with, histone, acetyl, transferase, and, histone, deacetylase, complexes])]). relacion([sujeto(['YY1', '(', 'Yin', and, 'Yang', 1, ')', is, a, 'multifunctional,', ubiquitously, 'expressed,', zinc, finger, protein, that, can]), verbo([act]), complemento([as, a, transcriptional, 'activator,', 'repressor,', or, initiator, element, binding, protein])]). relacion([sujeto(['Previous', studies]), verbo([have]), complemento([shown, that, 'YY1', modulates, the, activity, of, reporter, genes, driven, by, the, myelin, 'PLP', '(', proteolipid, 'protein)', '(', 'PLP1/Plp1)', promoter])]). relacion([sujeto(['However,', it, is, known, that, 'Plp1', intron, 1, 'DNA', contains, regulatory, elements, that, are]), verbo([required]), complemento([for, the, dramatic, increase, in, gene, 'activity,', coincident, with, the, active, myelination, period, of, 'CNS', '(', central, nervous, 'system)', development])]). relacion([sujeto(['The', intron, in, mouse, contains, multiple, prospective, 'YY1']), verbo([target]), complemento([sites, including, one, within, a, positive, regulatory, module, called, the, 'ASE', '(', 'anti-silencer/enhancer)', element])]). relacion([sujeto(['Results', presented, here, demonstrate, that, 'YY1']), verbo([has]), complemento([a, negative, effect, on, the, activity, of, a, 'Plp1-lacZ', fusion, gene, '[', 'PLP(+)Z]', in, an, immature, oligodendroglial, cell, line, '(', 'Oli-neu)', that, is, mediated, through, sequences, present, in, 'Plp1', intron, 1, 'DNA'])]). relacion([sujeto(['Yet', 'YY1', does, not]), verbo([bind]), complemento([to, its, alleged, site, in, the, 'ASE', '(', even, though, the, protein, is, capable, of, recognizing, a, target, site, in, the, 'promoter),', indicating, that, the, 'down-regulation', of, 'PLP(+)Z', activity, by, 'YY1', in, 'Oli-neu', cells, does, not, occur, through, a, direct, interaction, of, 'YY1', with, the, 'ASE', sequence])]). relacion([sujeto(['Previous', studies, with, 'Yy1', conditional, knockout, mice]), verbo([have]), complemento([demonstrated, that, 'YY1', is, essential, for, the, differentiation, of, oligodendrocyte, progenitors])]). relacion([sujeto(['Nevertheless,', the, current, study]), verbo([suggests]), complemento([that, 'YY1', functions, as, a, repressor, '(', not, an, 'activator)', of, 'Plp1', gene, expression, in, immature, oligodendrocytes])]). relacion([sujeto([miRNAs]), verbo([have]), complemento([the, potential, to, act, on, diverse, downstream, 'genes,', and, miRNA, signatures, of, 'HPV-infected', tissues, may, provide, insight, into, 'HPV-related', carcinogenesis])]). relacion([sujeto(['We', also]), verbo([found]), complemento([that, 'YY1', and, 'CDK6', were, both, positively, correlated, with, 'E6/E7', 'RNA', expression, and, targeted, by, 'tumour-suppressive', 'miR-29'])]). relacion([sujeto(['Taken', 'together,', our, results]), verbo([suggest]), complemento([that, 'HPVs', have, oncogenic, properties, at, least, in, part, by, reshaping, the, milieu, of, cellular, miRNAs])]). relacion([sujeto(['miR-29', restrains, cell, cycle, progression, and]), verbo([induces]), complemento([apoptosis, via, 'YY1', and, 'CDK6', promoting, malignant, transformation, induced, by, 'HPV,', although, the, abnormality, of, 'miR-29', in, 'HPV-infected', cells, might, be, regulated, in, an, indirect, way])]). relacion([sujeto(['Genomic', imprinting, is, an, evolutionary]), verbo([conserved]), complemento([mechanism, of, epigenetic, gene, regulation, in, placental, mammals, that, results, in, silencing, of, one, of, the, parental, alleles])]). relacion([sujeto(['In', order, to, decipher, interactions, between, 'allele-specific', 'DNA', methylation, of, imprinted, genes, and, evolutionary, 'conservation,', we, performed, a, 'genome-wide', comparative, investigation, of, genomic, sequences, and, highly]), verbo([conserved]), complemento([elements, of, imprinted, genes, in, human, and, mouse])]). relacion([sujeto(['Evolutionarily']), verbo([conserved]), complemento([elements, in, imprinted, regions, differ, from, those, associated, with, autosomal, genes, in, various, ways])]). relacion([sujeto(['Whereas', for, maternally]), verbo([expressed]), complemento([genes, strong, divergence, of, 'protein-encoding', sequences, is, most, 'prominent,', paternally, expressed, genes, exhibit, substantial, conservation, of, coding, and, noncoding, sequences])]). relacion([sujeto(['Interestingly,', paternally, and, maternally]), verbo([expressed]), complemento([genes, can, be, distinguished, by, differences, in, 'G+C', and, 'CpG', contents, that, might, be, associated, with, unusual, epigenetic, features])]). relacion([sujeto(['Especially', noncoding]), verbo([conserved]), complemento([elements, of, paternally, expressed, genes, are, exceptionally, 'G+C', and, 'CpG', rich])]). relacion([sujeto(['We', also]), verbo([found]), complemento([a, moderate, enrichment, of, 'YY1', and, 'CTCF', binding, sites, in, imprinted, regions, and, identified, several, short, sequence, motifs, in, highly, conserved, elements, that, might, act, as, additional, regulatory, elements])]). relacion([sujeto(['We', discovered, several, novel]), verbo([conserved]), complemento(['DNA', features, that, might, be, related, to, 'allele-specific', 'DNA', methylation])]). relacion([sujeto(['Our', results, hint, at, reduced, 'CpG', deamination, rates, in, imprinted, 'regions,', which, affects, mostly, noncoding]), verbo([conserved]), complemento([elements, of, paternally, expressed, genes])]). relacion([sujeto(['Pronounced', differences, between, maternally, and, paternally]), verbo([expressed]), complemento([genes, imply, specific, modes, of, evolution, as, a, result, of, differences, in, epigenetic, features, and, a, special, response, to, selective, pressure])]). relacion([sujeto(['In', 'addition,', our, data, support, the, potential, role, of, intronic, 'CpG', islands, as, epigenetic, key, regulatory, elements, and]), verbo([suggest]), complemento([that, evolutionary, conserved, 'LINE-1', elements, fulfill, regulatory, functions, in, imprinted, regions])]). relacion([sujeto(['The', monoclonal, antibody, rituximab, specifically]), verbo([targets]), complemento([the, 'CD20', antigen, and, sensitizes, 'B-cell', lymphoma, cells, to, standard, anticancer, drugs])]). relacion([sujeto(['In', the, present, 'investigation,', we, 'analyzed,', whether, a, combination, of, rituximab, and, artesunate, may]), verbo([act]), complemento([in, a, complementary, manner, and, eventually, synergize, in, tumor, cell, killing])]). relacion([sujeto(['While', rituximab, alone, was, minimally, 'cytotoxic,', rituximab]), verbo([increased]), complemento([cytotoxicity, to, artesunate, in, 'Ramos', cells])]). relacion([sujeto(['Artesunate']), verbo([induced]), complemento(['apoptosis,', induced, 'Fas/CD95', expression, and, the, formation, of, reactive, oxygen, species, '(', 'ROS)', and, resulted, in, a, breakdown, of, mitochondrial, membrane, potential])]). relacion([sujeto(['Rituximab']), verbo([increased]), complemento(['Fas/CD95', expression, and, 'ROS', formation, and, decreased, mitochondrial, membrane, potential, ultimately, leading, to, increased, apoptosis, induced, by, artesunate])]). relacion([sujeto(['YY1', and, 'Sp1', were, 'down-regulated', and, 'Fas/CD95', was, 'up-regulated', by, rituximab, and, artesunate, indicating, that, artesunate]), verbo([activated]), complemento([the, 'Fas/CD95', pathway, and, that, rituximab, increased, the, susceptibility, of, tumor, cells, to, 'artesunate-induced', apoptosis])]). relacion([sujeto(['The', antibody]), verbo([decreased]), complemento(['artesunate-induced', 'up-regulation', of, catalase, expression, and, increased, 'artesunate-induced', 'down-regulation', of, glutathione, 'S-transferase-phi', expression])]). relacion([sujeto(['In', a, humid, milieu, such, as, mucosal, 'surfaces,', pollen, grains, do, not, only]), verbo([release]), complemento([allergens, but, also, proinflammatory, and, immunomodulatory, 'lipids,', termed, 'pollen-associated', lipid, mediators])]). relacion([sujeto(['Among', 'these,', the, 'E(1)-phytoprostanes', '(', 'PPE(1))', were, identified, to]), verbo([modulate]), complemento([dendritic, cell, '(', 'DC)', 'function:', 'PPE(1)', inhibit, the, 'DC\'s', capacity, to, produce, 'IL-12', and, enhance, 'DC', mediated, 'T(H)2', polarization, of, naive, 'T', cells])]). relacion([sujeto(['The', 'mechanism(s)', by, which, 'PPE(1)']), verbo([act]), complemento([on, 'DC', remained, elusive])]). relacion([sujeto(['Aqueous', birch, pollen, extracts]), verbo([induced]), complemento([a, marked, cAMP, response, in, 'DC', that, could, be, blocked, partially, by, 'EP2', and, 'EP4', antagonists])]). relacion([sujeto(['In', 'contrast,', 'PPE(1)', hardly]), verbo([induced]), complemento([cAMP, and, the, inhibitory, effect, on, 'IL-12', production, was, mostly, independent, of, 'EP2', and, 'EP4'])]). relacion([sujeto(['Instead,', 'PPE(1)']), verbo([inhibited]), complemento([the, 'LPS-induced', production, of, 'IL-12', p70, by, a, mechanism, involving, the, nuclear, receptor, 'PPAR-gamma'])]). relacion([sujeto(['Finally,', 'PPE(1)', efficiently, blocked, 'NF-kappaB', signaling, in, 'DCs', by]), verbo([inhibiting]), complemento(['IkappaB-alpha', 'degradation,', translocation, of, p65, to, the, 'nucleus,', and, binding, to, its, target, 'DNA', elements])]). relacion([sujeto(['We', conclude, that, 'pollen-derived', 'PPE(1)']), verbo([modulate]), complemento(['DC', function, via, 'PPAR-gamma', dependent, pathways, that, lead, to, inhibition, of, 'NFkappaB', activation, and, result, in, reduced, 'DC', 'IL-12', production, and, consecutive, 'T(H)2', polarization])]). relacion([sujeto(['As', already, widely, 'studied,', 'Cyclooxygenase-2', '(', 'COX-2)', is, a, key, enzyme, for, prostaglandin, 'E2', '(', 'PGE(2))', 'production,', which]), verbo([induces]), complemento([the, nuclear, factor, kappa, 'B', '(', 'NFkappaB)', activation, and, is, beneficial, to, fracture, healing])]). relacion([sujeto(['Interestingly,', 'LPS', could]), verbo([induce]), complemento([osteoblasts, proliferation, through, increasing, 'NFkappaB', activation, and, translocation])]). relacion([sujeto(['This', induction, was, not, related, to, 'COX-2', 'expression,']), verbo([suggesting]), complemento([that, 'LPS-induced', 'NFkappaB', activation, is, independent, of, 'COX-2'])]). relacion([sujeto(['It', is, possible, that, low, concentration, of, 'LPS', can]), verbo([act]), complemento([as, a, stimulating, factor, of, the, 'NFkappaB', pathway, in, nonstimulated, cells, such, as, osteoblasts])]). relacion([sujeto(['These', studies]), verbo([provide]), complemento([insight, into, a, potential, mechanism, by, which, 'LPS', can, affect, bone, tissue, repair, in, the, initial, phase, of, inflammation])]). relacion([sujeto(['Human', 'CCAAT/enhancer-binding', protein, delta, '(', 'CEBPD)']), verbo([has]), complemento([been, reported, as, a, tumor, suppressor, because, it, both, induces, growth, arrest, involved, in, differentiation, and, plays, a, crucial, role, as, a, regulator, of, 'pro-apoptotic', gene, expression])]). relacion([sujeto(['Suppressor', of, zeste, 12, '(', 'SUZ12),', a, component, of, the, polycomb, repressive, complex, 2, '(', 'PRC2),', silences, 'CEBPD', promoter, 'activity,']), verbo([enhancing]), complemento([the, methylation, of, exogenous, 'CEBPD', promoter, through, the, proximal, 'CpG', islands])]). relacion([sujeto(['We', further, demonstrated, that, 'Yin-Yang-1', '(', 'YY1)', physically]), verbo([interacts]), complemento([with, 'SUZ12', and, can, act, as, a, mediator, to, recruit, the, polycomb, group, proteins, and, 'DNA', methyltransferases, to, participate, in, the, 'CEBPD', gene, silencing, process])]). relacion([sujeto(['Expression', of, 'VASAP-60', mRNA, showed, a, 2.4, -, fold]), verbo([increase]), complemento(['(', 'P<0'])]). relacion([sujeto(['The', -, 53, /, +, 16, bp, fragment, '(', +, 1, =, transcription, start, 'site)']), verbo([conferred]), complemento([minimal, promoter, activity, whereas, activator, and, repressor, elements, were, located, in, the, -, 200, /, -, 53, bp, and, -, 653, /, -, 200, bp, 'fragments,', respectively])]). relacion([sujeto(['Analysis', of, 'cis-acting', elements, in, the, -, 200, /, -, 53, bp, activation, domain, revealed, by, gel, shift, assays, and, chromatin, immunoprecipitation, assay, that, transcription, factor, 'YY1']), verbo([binds]), complemento([to, 'VASAP-60', promoter])]). relacion([sujeto(['This', study, is, the, first, to]), verbo([report]), complemento([that, 'VASAP-60', is, 'up-regulated', in, granulosa, cells, of, dominant, 'follicles,', to, document, the, primary, structure, of, the, bovine, 'VASAP-60', gene, and, 'promoter,', and, to, demonstrate, that, 'YY1', binds, to, the, 'VASAP-60', proximal, promoter, and, may, act, as, a, positive, transcriptional, regulator])]). relacion([sujeto(['Synaptotagmin', 'XI', '(', 'Syt11)', is, a, member, of, the, synaptotagmin, 'family,', which, is, localized, in, cells, either, in, synaptic, vesicles, or, the, cellular, 'membrane,', and, is, known, to]), verbo([act]), complemento([as, a, calcium, sensor])]). relacion([sujeto(['The', 'Syt11', gene, is, located, on, chromosome, locus, 1, 'q21-q22,', which, was, previously]), verbo([reported]), complemento([as, a, major, susceptibility, locus, of, familial, schizophrenia])]). relacion([sujeto(['We']), verbo([found]), complemento([that, the, transcriptional, activity, of, the, gene, is, affected, by, the, number, of, 33, -, bp, 'repeats,', which, include, an, 'Sp1', binding, 'site,', suggesting, that, the, excessive, expression, of, 'Syt11', can, be, associated, with, schizophrenia])]). relacion([sujeto(['Amelogenin', proteins, are, essential, in, the, control, of, enamel, biomineralization, and, the, amelogenin, gene, therefore, is, spatiotemporally]), verbo([regulated]), complemento([to, ensure, proper, amelogenin, protein, expression])]). relacion([sujeto(['In', this, 'study,', we, examined, the, role, of, sumoylation, to, alter, 'CCAAT/enhancer-binding', protein, alpha, '(', 'C/EBPalpha)', 'activity,', and, performed, a, search, using, a, 'protein/DNA', array, system, for, other, proteins, that]), verbo([act]), complemento(['co-operatively', with, 'C/EBPalpha', to, alter, amelogenin, expression])]). relacion([sujeto(['We', observed, that, 'C/EBPalpha', was, modified, by, 'sumoylation,', and, that, this, modification, played, an, indirect, inhibitory, role, on, the, regulation, of, 'C/EBPalpha', activity, which, appeared, to]), verbo([act]), complemento([through, other, transcription, factors])]). relacion([sujeto(['The', 'protein/DNA', array, allowed, us, to, single, out, the, transcription, 'factor,', 'YY1,', which]), verbo([acts]), complemento([in, the, absence, of, direct, 'DNA', binding, to, repress, both, the, basal, amelogenin, promoter, activity, and, 'C/EBPalpha-mediated', transactivation])]). relacion([sujeto(['The', multifunctional, transcription, factor, 'Yin', 'Yang', 1, '(', 'YY1)', is, a, complex, protein, that]), verbo([has]), complemento([been, shown, to, play, pivotal, roles, in, 'development,', 'differentiation,', cellular, proliferation, and, apoptosis])]). relacion([sujeto(['It', can]), verbo([act]), complemento([as, a, transcriptional, 'repressor,', an, 'activator,', or, an, initiator, element, binding, protein, that, directs, and, initiates, transcription, of, numerous, cellular, and, viral, genes])]). relacion([sujeto(['Because', the, expression, and, function, of, 'YY1', are, known, to, be, intimately]), verbo([associated]), complemento([with, 'cell-cycle', 'progression,', the, physiological, significance, of, 'YY1', activity, has, recently, been, applied, to, models, of, cancer, biology])]). relacion([sujeto(['Several', lines, of, evidence, imply, that, 'YY1', expression, 'and/or', activation, is]), verbo([associated]), complemento([with, 'tumourigenesis,', in, addition, to, its, regulatory, roles, in, normal, biological, processes])]). relacion([sujeto(['Heme', oxygenase, '(', 'HO)-1', is, a, stress, response, 'protein,', which]), verbo([confers]), complemento([cytoprotection, against, oxidative, injury, and, provides, a, vital, function, in, maintaining, tissue, homeostasis])]). relacion([sujeto(['Molecular', mechanisms]), verbo([involved]), complemento([in, the, inducible, transcription, of, 'ho-1', occurring, in, response, to, numerous, and, diverse, stressful, conditions, have, remained, elusive])]). relacion([sujeto(['Since', the, discovery, of, 'E1', and, 'E2,', the, two, upstream, enhancers]), verbo([regulating]), complemento([induction, of, 'ho-1', transcription, in, 1989, ',', there, have, been, many, studies, dealing, with, molecular, mechanisms, involved, in, enhancing, 'HO-1', expression])]). relacion([sujeto(['In', this, 'commentary,', recent, advances, in, our, understanding, of, the, mechanisms]), verbo([involved]), complemento([in, the, induction, of, 'HO-1', expression, in, mammalian, cells, are, summarized, with, some, supportive, results, reported, by, others])]). relacion([sujeto(['Currently', available, data, indicate, that, activation, of, 'ho-1', transcription]), verbo([involves]), complemento([both, the, heme, '(', native, 'substrate)-dependent', selective, alleviation, of, repressor, and, the, oxidative, 'stress-dependent', activation, of, transcriptional, activator])]). relacion([sujeto(['The', 'stress-released', 'free-heme', '(', 'HO-1', 'substrate)', from, hemoproteins]), verbo([involved]), complemento([in, causing, oxidative, stress, itself, appears, to, act, as, a, molecular, switch, controlling, the, 'repressor-', activator, antagonism, on, the, enhancer, sequences, of, 'ho-1'])]). relacion([sujeto(['The', ubiquitous, transcription, factor, 'Yin', 'Yang', 1, '(', 'YY1)', is, known, to]), verbo([have]), complemento([a, fundamental, role, in, normal, biologic, processes, such, as, 'embryogenesis,', 'differentiation,', 'replication,', and, cellular, proliferation])]). relacion([sujeto(['YY1', exerts, its, effects, on, genes]), verbo([involved]), complemento([in, these, processes, via, its, ability, to, 'initiate,', 'activate,', or, repress, transcription, depending, upon, the, context, in, which, it, binds])]). relacion([sujeto(['Mechanisms', of, action, include, direct, activation, or, 'repression,', indirect, activation, or, repression, via, cofactor, 'recruitment,', or, activation, or, repression, by, disruption, of]), verbo([binding]), complemento([sites, or, conformational, 'DNA', changes])]). relacion([sujeto(['YY1', activity, is]), verbo([regulated]), complemento([by, transcription, factors, and, cytoplasmic, proteins, that, have, been, shown, to, abrogate, or, completely, inhibit, 'YY1-mediated', activation, or, 'repression;', 'however,', these, mechanisms, have, not, yet, been, fully, elucidated])]). relacion([sujeto(['Since', expression, and, function, of, 'YY1', are, known, to, be, intimately]), verbo([associated]), complemento([with, progression, through, phases, of, the, cell, 'cycle,', the, physiologic, significance, of, 'YY1', activity, has, recently, been, applied, to, models, of, tumor, biology])]). relacion([sujeto(['The', majority, of, the, data, are, consistent, with, the, hypothesis, that, 'YY1', overexpression, 'and/or', activation, is]), verbo([associated]), complemento([with, unchecked, cellular, 'proliferation,', resistance, to, apoptotic, 'stimuli,', tumorigenesis, and, metastatic, potential])]). relacion([sujeto(['Studies']), verbo([involving]), complemento([hematopoetic, 'tumors,', 'epithelial-based', 'tumors,', endocrine, organ, 'malignancies,', hepatocellular, 'carcinoma,', and, retinoblastoma, support, this, hypothesis])]). relacion([sujeto(['Molecular', mechanisms, that]), verbo([have]), complemento([been, investigated, include, 'YY1-mediated', downregulation, of, p53, 'activity,', interference, with, 'poly-ADP-ribose', 'polymerase,', alteration, in, 'c-myc', and, nuclear, 'factor-kappa', 'B', '(', 'NF-kappaB)', 'expression,', regulation, of, death, genes, and, gene, 'products,', and, differential, 'YY1', binding, in, the, presence, of, inflammatory, mediators])]). relacion([sujeto(['Taken', 'together,', these, findings]), verbo([provide]), complemento([strong, support, of, the, hypothesis, that, 'YY1,', in, addition, to, its, regulatory, roles, in, normal, biologic, 'processes,', may, possess, the, potential, to, act, as, an, initiator, of, tumorigenesis, and, may, thus, serve, as, both, a, diagnostic, and, prognostic, tumor, 'marker;', 'furthermore,', it, may, provide, an, effective, target, for, antitumor, chemotherapy, 'and/or', immunotherapy])]). relacion([sujeto(['Changes', in, the, expression, of, components, that, are, known, to, be, substrates, of, the, 'UbPS', and, that]), verbo([participate]), complemento([in, the, regulation, of, the, cell, death, process, were, also, studied])]). relacion([sujeto(['Addition', of, different, concentrations, of, 'C2', ceramide, to, cultured, 'ASTs', produced, an]), verbo([increase]), complemento([in, the, expression, of, the, 'Ub', gene, and, in, the, gene, that, encodes, 'E1,', one, of, the, enzymes, involved, in, the, ubiquitination, 'process,', without, any, changes, on, cell, viability])]). relacion([sujeto(['Immunocytochemical', studies, showed, an]), verbo([increase]), complemento([in, the, expression, of, 'Bcl-2', with, no, changes, in, cytochrome, c])]). relacion([sujeto(['Also,', there, was, an]), verbo([increase]), complemento([in, the, nuclear, reactivity, of, 'NFkappaB,', suggesting, a, translocation, of, this, factor, towards, the, nucleus])]). relacion([sujeto(['Western', blots, showed, a]), verbo([decrease]), complemento([in, 'IkappaB', and, its, phosphorylated, form, as, well, as, an, increase, in, 'Bcl-2', with, no, changes, in, cytochrome, c])]). relacion([sujeto(['All', of, these, compounds, appear, to, be]), verbo([acting]), complemento([as, possible, modulators, of, 'AST', responses, to, 'C2', ceramide])]). relacion([sujeto(['Our', results]), verbo([suggest]), complemento([that, in, 'AST', primary, 'cultures,', 'C2', 'ceramide,', at, the, concentrations, used, in, this, 'study,', does, not, produce, apoptosis])]). relacion([sujeto(['However,', it]), verbo([induces]), complemento([an, activation, of, the, 'UbPS,', probably, as, a, consequence, of, an, activation, of, phosphatases, and, 'kinases,', or, through, the, generation, of, reactive, oxygen, 'species,', which, act, as, triggering, signals, of, the, 'UbPS'])]). relacion([sujeto(['Prior', work]), verbo([has]), complemento([indicated, that, 'BMP', signals, act, in, concert, with, 'FGF8,', 'WNT11', and, 'WNT', antagonists, to, induce, the, formation, of, cardiac, tissue, in, the, vertebrate, embryo])]). relacion([sujeto(['In', an, effort, to, understand, how, these, signaling, pathways, control, the, expression, of, key, cardiac, 'regulators,', we]), verbo([have]), complemento([characterized, the, 'cis-regulatory', elements, of, the, chick, tinman, homolog, chick, 'Nkx2'])]). relacion([sujeto(['We']), verbo([find]), complemento([that, at, least, three, distinct, cardiac, activating, regions, '(', 'CARs)', of, chick, 'Nkx2'])]). relacion([sujeto([5, cooperate, to]), verbo([regulate]), complemento([early, expression, in, the, cardiac, crescent, and, later, segmental, expression, in, the, developing, heart])]). relacion([sujeto(['Adjacent', 'YY1', and, 'SMAD-binding', sites, within, 'CAR3', constitute, a, minimal, 'BMP', response, 'element,', and, interaction, of, 'SMAD1/4', with, the, 'N', terminus, of, 'YY1', is]), verbo([required]), complemento([for, 'BMP-mediated', induction, of, 'CAR3'])]). relacion([sujeto(['Our', data]), verbo([suggest]), complemento([that, 'BMP-mediated', activation, of, this, regulatory, region, reflects, both, the, induction, of, 'GATA', genes, by, 'BMP', 'signals,', as, well, as, modulation, of, the, transcriptional, activity, of, 'YY1', by, direct, interaction, of, this, transcription, factor, with, 'BMP-activated', 'SMADs'])]). relacion([sujeto(['Polycomb', group, '(', 'PcG)', genes, are]), verbo([required]), complemento([for, the, stable, repression, of, the, homeotic, genes, and, other, developmentally, regulated, genes])]). relacion([sujeto(['Yin', 'Yang', 1, '(', 'YY1),', a, vertebrate, homolog, of, the, 'Drosophila', 'PcG', pleiohomeotic, '(', 'Pho),', is, a, multifunctional, protein, that, can]), verbo([act]), complemento([as, a, repressor, or, activator, of, transcription])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, 'YY1', controls, 'antero-posterior', patterning, of, the, 'CNS', during, 'Xenopus', embryonic, development])]). relacion([sujeto(['Pleiohomeotic', '(', 'Pho),', the, only, known, 'sequence-specific', 'DNA-binding', 'PcG', 'protein,']), verbo([binds]), complemento([to, 'PREs', but, pho, mutants, show, only, mild, phenotypes, compared, with, other, 'PcG', mutants])]). relacion([sujeto(['Pho-like']), verbo([binds]), complemento([to, 'Pho-binding', sites, in, vitro, and, 'pho-like,', pho, double, mutants, show, more, severe, misexpression, of, homeotic, genes, than, do, the, single, mutants])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, 'Pho', and, 'Pho-like', act, redundantly, to, repress, homeotic, genes])]). relacion([sujeto(['Pc,', 'Psc,', 'Scm,', 'E(z)', and, 'Ph', remain]), verbo([bound]), complemento([to, polytene, chromosomes, at, most, sites, in, the, absence, of, 'Pho', and, 'Pho-like'])]). relacion([sujeto(['At', a, few, chromosomal, 'locations,', 'however,', some, of, the, 'PcG', proteins, are, no, longer, present, in, the, absence, of, 'Pho', and, 'Pho-like,']), verbo([suggesting]), complemento([that, 'Pho-like', and, 'Pho', may, anchor, 'PcG', protein, complexes, to, only, a, subset, of, 'PREs'])]). relacion([sujeto(['Alternatively,', 'Pho-like', and, 'Pho', may, not]), verbo([participate]), complemento([in, the, anchoring, of, 'PcG', 'complexes,', but, may, be, necessary, for, transcriptional, repression, mediated, through, 'PREs'])]). relacion([sujeto(['In', contrast, to, 'Pho', and, 'Pho-like,', removal, of, 'Trithorax-like/GAGA', factor, or, 'Zeste,', two, other, 'DNA-binding', proteins, implicated, in, 'PRE', 'function,', does, not]), verbo([cause]), complemento([misexpression, of, homeotic, genes, or, reporter, genes, in, imaginal, disks])]). relacion([sujeto(['Estrogens', can, upregulate, endothelial, nitric, oxide, synthase, '(', 'eNOS)', in, human, endothelial, cells, by]), verbo([increasing]), complemento([eNOS, promoter, activity, and, enhancing, the, binding, activity, of, the, transcription, factor, 'Sp1'])]). relacion([sujeto(['Resveratrol,', a, polyphenolic, phytoalexin]), verbo([found]), complemento([in, grapes, and, 'wine,', has, been, reported, to, act, as, an, agonist, at, the, estrogen, receptor])]). relacion([sujeto([eNOS, protein, expression, and, 'eNOS-derived', 'NO', production, were, also]), verbo([increased]), complemento([after, 'long-term', incubation, with, resveratrol])]). relacion([sujeto(['Resveratrol']), verbo([increased]), complemento([the, activity, of, the, eNOS, promoter, '(', 3.5, -, kb, 'fragment)', in, a, 'concentration-dependent', 'fashion,', with, the, essential, 'trans-stimulated', sequence, being, located, in, the, proximal, 263, bp, of, the, promoter, sequence])]). relacion([sujeto(['In', electrophoretic, mobility, shift, 'assays,']), verbo([nuclear]), complemento([extracts, from, 'resveratrol-incubated', 'EA'])]). relacion([sujeto([hy, 926, cells, showed, no]), verbo([enhanced]), complemento([binding, activity, of, the, eNOS, 'promoter-relevant', transcription, factors, 'Sp1,', 'GATA,', 'PEA3,', 'YY1,', or, 'Elf-1'])]). relacion([sujeto(['In', addition, to, its, 'long-term', effects, on, eNOS, 'expression,', resveratrol, also]), verbo([enhanced]), complemento([the, production, of, bioactive, 'NO', in, the, 'short-term', '(', after, a, 2, -, minute, 'incubation)'])]). relacion([sujeto(['During', 'adeno-associated', virus, '(', 'AAV)', type, 2, productive, 'infections,', the, p19, promoter, of, 'AAV', is]), verbo([activated]), complemento([by, the, 'AAV', 'Rep78', and, 'Rep68', proteins])]). relacion([sujeto(['Rep-induced', activation, of, p19, depends, on, the, presence, of, one, of, several, redundant, 'Rep']), verbo([binding]), complemento([elements, '(', 'RBEs)', within, the, p5, promoter, or, within, the, terminal, repeats, '(', 'TR)'])]). relacion([sujeto(['To', determine, how, a, 'Rep', complex]), verbo([bound]), complemento([at, p5, induces, transcription, at, 'p19,', we, made, a, series, of, p19, promoter, chloramphenicol, acetyltransferase, constructs, in, which, the, p5, 'RBE', was, inserted, at, different, locations, upstream, or, downstream, of, the, p19, mRNA, start, site])]). relacion([sujeto(['The', 'RBE']), verbo([acted]), complemento([like, a, repressor, element, at, most, positions, in, the, presence, of, both, 'Rep', and, adenovirus, '(', 'Ad),', and, the, level, of, repression, increased, dramatically, as, the, 'RBE', was, inserted, closer, to, the, p19, promoter])]). relacion([sujeto(['To', understand, how, the, 'Rep-RBE', complex, within, p5]), verbo([activated]), complemento(['p19,', we, considered, the, possibility, that, its, role, was, to, function, as, an, architectural, protein, whose, purpose, was, to, bring, other, p5, transcriptional, elements, to, the, p19, promoter])]). relacion([sujeto(['In', order, to, address, this, 'possibility,', we, replaced, both, the, p5, 'RBE', and, the, p19, 'Sp1', site, with, 'GAL4']), verbo([binding]), complemento([sites])]). relacion([sujeto(['The', modified, 'GAL4-containing', constructs, were, cotransfected, with, plasmids, that]), verbo([expressed]), complemento(['GAL4', fusion, proteins, capable, of, interacting, through, p53, and, 'T-antigen', '(', 'T-ag)', protein, domains])]). relacion([sujeto(['This']), verbo([suggested]), complemento([that, the, primary, role, of, the, p5, 'RBE', and, the, p19, 'Sp1', sites, was, to, act, as, a, scaffold, for, bringing, transcription, complexes, in, the, p5, promoter, into, close, proximity, with, the, p19, promoter])]). relacion([sujeto(['In', 'addition,', both, basal, p19, activity, and, activity, in, the, presence, of, 'Ad']), verbo([increased]), complemento([when, the, 'YY1-60', site, was, mutated, even, in, the, absence, of, 'Rep', or, 'GAL4', fusion, proteins])]). relacion([sujeto(['Therefore,', there, are, likely, to, be, alternative, 'p5-p19', interactions, that, are, 'Rep', independent, in, which, the, 'YY1-60', complex]), verbo([inhibits]), complemento([p19, transcription])]). relacion([sujeto(['The', functional, role, of, the, osteoblast]), verbo([nuclear]), complemento([matrix, has, been, a, matter, of, supposition])]). relacion([sujeto(['Its', presumed, function, as, an, architectural, agent, of, transcription, derives, primarily, from, the, low, solubility, of]), verbo([nuclear]), complemento([matrix, proteins, and, their, typical, localization, into, discrete, subnuclear, domains])]). relacion([sujeto(['In', addressing, how, the]), verbo([nuclear]), complemento([matrix, regulates, skeletal, 'genes,', the, authors, compare, 'Nmp4,', 'Cbfal,', and, 'YY1', for, the, purpose, of, profiling, osteoblast, nuclear, matrix, transcription, factors])]). relacion([sujeto(['All', three, proteins, contribute, to, the, transcription, of, 'ECM', genes, and, partition, into, the, osteoblast]), verbo([nuclear]), complemento([matrix, via, a, nuclear, matrix, targeting, domain])]). relacion([sujeto(['The', authors, propose, that, osteoblast]), verbo([nuclear]), complemento([matrix, transcription, factors, involved, in, 'ECM', regulation, generally, have, the, capacity, to, alter, 'DNA', geometry, and, reciprocally, respond, to, 'DNA', as, an, allosteric, ligand])]). relacion([sujeto(['This', may, allow, these, proteins, to, adapt, to, the, local]), verbo([nuclear]), complemento([architecture, and, generate, the, pattern, of, regulation, specified, by, that, architecture, via, unmasking, of, the, appropriate, transactivation, domains])]). relacion([sujeto(['Osteoblast']), verbo([nuclear]), complemento([matrix, transcription, factors, may, also, act, as, transcriptional, adaptor, molecules, by, supporting, the, formation, of, higher, order, protein, complexes, along, target, gene, promoters])]). relacion([sujeto(['The', genes, encoding, all, three, proteins, considered, here]), verbo([have]), complemento([trinucleotide, repeat, 'domains,', although, the, significance, of, this, is, unclear])]). relacion([sujeto(['There', is, no, canonical]), verbo([nuclear]), complemento([matrix, binding, 'motif,', but, 'finger-like', structures, may, be, suited, for, anchoring, proteins, to, discrete, subnuclear, domains])]). relacion([sujeto(['Finally,', the, ability, to, leave, the, osteoblast]), verbo([nuclear]), complemento([matrix, may, be, as, important, to, the, function, of, some, nuclear, matrix, transcription, factors, as, their, association, with, this, subcompartment])]). relacion([sujeto(['The', receptor, activator, of]), verbo([nuclear]), complemento([factor, '(', 'NF)-kappaB', ligand, '[', 'RANKL;', also, known, as, tumor, necrosis, 'factor-related', 'activation-induced', 'cytokine,', osteoprotegerin, 'ligand,', and, osteoclast, differentiation, 'factor]', is, known, to, bind, with, the, receptor, activator, of, 'NF-kappaB', '(', 'RANK)', and, act, not, only, as, a, key, factor, for, osteoclastogenesis, but, also, as, a, regulator, of, lymphocyte, development])]). relacion([sujeto(['In', this, 'study,', we]), verbo([found]), complemento([two, additional, isoforms, of, 'RANKL'])]). relacion([sujeto(['RANKL', 2]), verbo([has]), complemento([a, shorter, intracellular, domain, than, the, original, 'RANKL', '(', 'RANKL', 1, ')', ',', and, 'RANKL', 3, lacks, a, transmembrane, domain, and, was, thought, to, act, as, a, soluble, form])]). relacion([sujeto(['In', the, bone, marrow, stromal, cell, line, 'ST2', and, preosteoblastic, cell, line, 'MC3T3-E1,', all, three, 'RANKL', isoforms, were, 'detected,', but, the, expression, of, 'RANKL', 2, was, preferentially]), verbo([suppressed]), complemento([by, treatment, with, 1, 'alpha,25-dihydroxyvitamin', 'D(3)', and, dexamethasone])]). relacion([sujeto(['The', presence, of, multiple, 'RANKL-RANK', pathways]), verbo([suggests]), complemento([a, more, complicated, 'RANKL-RANK', system, for, osteoclastogenesis, or, 'T', cell, differentiation, than, previously, thought])]). relacion([sujeto(['We']), verbo([have]), complemento([previously, shown, that, 'CCAAT', displacement, protein, '(', 'CDP)', binds, the, 'differentiation-induced', 'HPV-6', 'E1', promoter, and, negatively, regulates, its, activity, in, undifferentiated, cells, '(', 'W'])]). relacion([sujeto(['Using', electrophoretic, mobility, shift, assays, '(', 'EMSAs),', we, now]), verbo([report]), complemento([that, 'Yin', 'Yang', 1, '(', 'YY1),', a, multifunctional, protein, that, can, act, as, a, transcriptional, activator, or, repressor, and, that, can, also, inhibit, 'HPV', replication, in, 'vitro,', binds, the, 'HPV-6', 'E1', promoter])]). relacion([sujeto(['EMSAs,', using, subfragments, of, the, promoter, as, 'competitors,', showed, that, the, 'YY1']), verbo([binding]), complemento([site, is, located, at, the, 5, '\'', end, of, the, 'E1', promoter])]). relacion([sujeto(['When', a, putative, 'YY1', site, was, 'mutated,', the, ability, of, 'YY1', to]), verbo([bind]), complemento([was, greatly, decreased])]). relacion([sujeto(['The', activity, of, the, mutated, 'E1', 'promoter,', monitored, with, the, reporter, gene, 'luciferase,', was, threefold, greater, than, that, of, the, 'wild-type', 'promoter,']), verbo([suggesting]), complemento([that, 'YY1', negatively, regulates, 'HPV-6', 'E1', promoter, activity])]). relacion([sujeto(['Nuclear', extracts, from, differentiated, keratinocytes, showed]), verbo([decreased]), complemento([binding, of, 'YY1', to, the, 'wild-type', promoter])]). relacion([sujeto(['Consistent', with, 'this,', in, differentiated, 'keratinocytes,', the, activity, of, the, transfected, luciferase, gene]), verbo([transcribed]), complemento([from, the, mutated, promoter, was, comparable, to, that, of, the, 'wild-type', 'promoter;', both, promoters, were, 'up-regulated', in, differentiated, keratinocytes, compared, to, undifferentiated, cells])]). relacion([sujeto(['These', data]), verbo([suggest]), complemento([that, 'YY1', functions, in, undifferentiated, keratinocytes, but, not, in, differentiated, keratinocytes])]). relacion([sujeto(['Both', the, 'wild-type', and, mutated, promoters, could, be, negatively]), verbo([regulated]), complemento([by, overexpression, of, a, plasmid, encoding, 'CDP'])]). relacion([sujeto(['In', 'contrast,', only]), verbo([binding]), complemento([of, 'CDP', was, detected, using, the, 'E1', promoter, of, the, 'high-risk', 'HPV-31'])]). relacion([sujeto(['Deletion', of, upstream, sequence, from, -, 635]), verbo([increased]), complemento([basal, activity, of, the, promoter, by, at, least, 'four-fold,', an, increase, that, was, maintained, when, 'PU'])]). relacion([sujeto(['Mutagenesis', identified, a, suppressor, element, between, -, 635, and, -, 642, from, the, transcriptional, start, site, and, an, oligonucleotide, representing, this, sequence, was, retarded, by]), verbo([nuclear]), complemento([cell, protein])]). relacion([sujeto(['TNFalpha', '(', 1, 'ng/ml),', 'PTH', '(', 5, 'x10(-8)', 'M),', and, 'IL-1alpha', '(', 100, 'pg/ml),', which]), verbo([increased]), complemento(['MCSF', protein, 'secretion,', failed, to, enhance, the, transcriptional, rate, of, the, 'full-length', promoter])]). relacion([sujeto(['TNFalpha', was, able, to]), verbo([stimulate]), complemento([transcription, of, a, heterologous, reporter, transfected, into, 'COS-7', containing, multiple, copies, of, the, murine, 'MCSF', 'NFkappaB', site, inserted, before, a, minimal, promoter])]). relacion([sujeto(['In', 'contrast,', deletion, of, the, same, 'NFkappaB', response, element]), verbo([increased]), complemento([basal, activity, in, the, native, promoter])]). relacion([sujeto(['Thus,', the, 'NFkappaB', sequence, may]), verbo([act]), complemento([as, a, negative, regulator, in, the, context, of, the, endogenous, promoter])]). relacion([sujeto(['Our', results, indicate, that, constitutive, transcriptional, activity]), verbo([conferred]), complemento([by, the, 'MCSF', promoter, may, be, damped, by, a, suppressor, protein])]). relacion([sujeto(['The', transcription, factor, 'YY1', is, a, complex, protein, that, is]), verbo([involved]), complemento([in, repressing, and, activating, a, diverse, number, of, promoters])]). relacion([sujeto(['Numerous', studies]), verbo([have]), complemento([attempted, to, understand, how, this, one, factor, can, act, both, as, a, repressor, and, an, activator, in, such, a, wide, set, of, different, contexts])]). relacion([sujeto(['The', fact, that, 'YY1']), verbo([interacts]), complemento([with, a, number, of, key, regulatory, proteins, '(', e])]). relacion([sujeto(['TBP,', 'TFIIB,', 'TAFII55,', 'Sp1,', and, 'E1A)']), verbo([has]), complemento([suggested, that, these, interactions, are, important, for, determining, which, particular, function, of, 'YY1', is, displayed, at, a, specific, promoter])]). relacion([sujeto(['Two', groups, of, 'proteins,', previously, known, to, function, as, corepressors, and, 'coactivators,', that, now, seem, likely, to]), verbo([modulate]), complemento(['YY1\'s', 'functions,', are, the, histone, deacetylases, '(', 'HDAC)', and, histone, acetyltransferases, '(', 'HAT)'])]). relacion([sujeto(['When', these, enzymes, are, directed, to, a, promoter, through, a, 'DNA']), verbo([binding]), complemento([factor, such, as, 'YY1,', that, promoter, can, be, activated, or, repressed])]). relacion([sujeto(['This', review, will, discuss, the, recent, work, dealing, with, the, different, proteins, that]), verbo([interact]), complemento([with, 'YY1,', with, particular, emphasis, on, ones, that, modify, 'chromatin,', and, how, they, could, be, involved, in, regulating, 'YY1\'s', activities])]). relacion([sujeto(['PcG', proteins, are, thought, to]), verbo([act]), complemento([by, binding, as, multiprotein, complexes, to, 'DNA', through, 'Polycomb', group, response, elements, '(', 'PREs);', 'however,', specific, 'DNA', binding, has, not, been, demonstrated, for, any, of, the, 'PcG', proteins])]). relacion([sujeto(['We']), verbo([have]), complemento([identified, a, 'sequence-specific', 'DNA', binding, protein, that, interacts, with, a, 'PRE', from, the, 'Drosophila', engrailed, gene])]). relacion([sujeto(['We', propose, that, 'PHO']), verbo([acts]), complemento([to, anchor, 'PcG', protein, complexes, to, 'DNA'])]). relacion([sujeto(['Human', papillomavirus, type, 8, '(', 'HPV-8)', is, a, strictly, cutaneous, oncogenic, virus, known, to]), verbo([induce]), complemento([malignant, skin, lesions, in, epidermodysplasia, verruciformis, patients])]). relacion([sujeto(['Using', 'DNase', 'I', footprinting, and, gel, retardation, tests, it, could, be, demonstrated, that, three, of, these, motifs, indeed]), verbo([act]), complemento([as, 'YY1', binding, sites])]). relacion([sujeto(['To', test, their, functional, relevance, for, 'P175', 'activity,', engineered, 'YY1']), verbo([binding]), complemento([site, mutants, were, analysed, in, the, context, of, a, 'P175', test, vector, using, transient, expression, assays, with, human, keratinocytes])]). relacion([sujeto(['YY1', turned, out, to, exert, both, positive, and, negative, effects, upon, the, activity, of, the, 'HPV-8', 'E6', 'promoter;']), verbo([binding]), complemento([of, 'YY1', to, a, site, upstream, of, the, 'promoter\'s', 'cap-position', '(', 'BS1)', activated, 'transcription,', whereas, the, downstream, site, '(', 'BS2)', mediated, repression])]). relacion([sujeto(['The', second, downstream, 'YY1']), verbo([binding]), complemento([site, '(', 'BS3)', seemed, to, play, an, auxiliary, 'role,', enhancing, the, negative, effect, of, 'YY1', 'BS2'])]). relacion([sujeto(['These', observations, define, 'YY1', as, an, important, cellular, protein]), verbo([involved]), complemento([in, the, control, of, 'E6', oncogene, expression, of, the, 'skin-specific', '\'', high, 'risk\'', 'HPV-8', and, emphasize, the, potential, regulatory, role, of, sequences, located, downstream, of, the, transcription, start, site])]). relacion([sujeto(['Disruption', of, 'Epstein-Barr', virus, latency, is]), verbo([induced]), complemento([by, expression, of, either, the, 'BZLF1', '(', in, 'B', cells, and, epithelial, 'cells)', or, 'BRLF1', '(', in, epithelial, cells, 'only)', 'immediate-early', protein])]). relacion([sujeto(['Regulation', of, 'BZLF1', and, 'BRLF1', transcription, may, therefore]), verbo([modulate]), complemento([the, stringency, of, viral, latency])]). relacion([sujeto(['The', cellular, transcription, factor, 'YY1', negatively]), verbo([regulates]), complemento(['BZLF1', transcription])]). relacion([sujeto(['Here', we, show, that, the, 'BRLF1', promoter, '(', 'Rp)', sequences, from, -, 206, to, -, 227, '(', relative, to, the, mRNA, start, 'site)', and, from, -, 7, to, +, 6, are, directly]), verbo([bound]), complemento([by, 'YY1'])]). relacion([sujeto(['Mutation', of, the, upstream, 'YY1']), verbo([binding]), complemento([site, increases, constitutive, 'Rp', activity, in, epithelial, cells, and, 'B', 'cells,', while, mutation, of, the, downstream, 'YY1', binding, site, does, not, significantly, affect, 'Rp', activity])]). relacion([sujeto(['Negative', regulation, of, 'BZLF1', and, 'BRLF1', transcription, by, 'YY1', may]), verbo([act]), complemento([to, maintain, viral, latency])]). relacion([sujeto(['YY1', is, ubiquitously]), verbo([expressed]), complemento([zinc, finger, 'DNA', binding, protein])]). relacion([sujeto(['It', can]), verbo([act]), complemento([as, a, transcriptional, repressor, or, activator, 'and,', when, binding, at, the, initiator, 'element,', as, a, component, of, the, basal, transcription, complex])]). relacion([sujeto(['Binding', sites, for, 'YY1']), verbo([have]), complemento([been, reported, in, a, wide, variety, of, promoters, and, they, exhibit, substantial, diversity, in, their, sequence])]). relacion([sujeto(['To', better, understand, how, 'YY1']), verbo([interacts]), complemento([with, 'DNA', and, to, be, able, to, predict, the, presence, of, 'YY1', sites, in, a, more, comprehensive, 'fashion,', we, have, selected, 'YY1', binding, sites, from, a, random, pool, of, oligonucleotides])]). relacion([sujeto(['The', sites, display, considerable, 'heterogeneity,', but, contain, a]), verbo([conserved]), complemento([5, '\'', -, 'CAT-3\'', core, flanked, by, variable, 'regions,', generating, the, consensus, 5, '\'', -, '(', 'C/g/a)(G/t)(C/t/a)CATN(T/a)(T/g/c)-3\',', where, the, upper, case, letters, represent, the, preferred, base])]). relacion([sujeto(['We']), verbo([have]), complemento([evaluated, the, potential, role, of, prostaglandins, and, their, 'second-messenger', 'Cyclic', 'Adenosine', 'Monophosphate', '(', 'cAMP)', in, the, activation, of, 'interleukin-6', '(', 'IL-6)', promoter, regulatory, elements, leading, to, 'IL-6', expression, in, monocytic, cells])]). relacion([sujeto(['We', demonstrate, that, prostaglandins, of, the, 'E', series, and, their, 'second-messenger', cAMP]), verbo([induce]), complemento([the, 'IL-6', promoter, in, the, murine, monocytic, cell, line, 'PU5-1'])]). relacion([sujeto(['We', show, that, the, endogenous, 'IL-6', gene, is]), verbo([induced]), complemento([by, cAMP, as, 'well,', even, though, to, a, lesser, extent, than, by, 'LPS,', suggesting, distinctive, effects, of, cAMP, and, 'LPS', on, posttranscriptional, events])]). relacion([sujeto(['Mutations', eliminating, potential, transcription, factor]), verbo([binding]), complemento(['sites,', including, the, 'multiple-response', element, '(', 'MRE),', 'AP-1,', 'NF-IL6,', and, 'NF-kappaB', binding, 'sites,', significantly, 'reduce,', but, do, not, completely, 'abrogate,', inducibility, by, cAMP, or, prostaglandin, 'E1,', whereas, alterations, of, four, additional, putative, regulatory, elements, have, no, effects])]). relacion([sujeto(['In', 'contrast,', 'LPS-induced', promoter, activity, is, almost, completely, abolished, by, mutations, in, the, 'NF-kappaB']), verbo([binding]), complemento(['site,', suggesting, that, a, single, regulatory, element, is, crucial, for, inducibility, by, 'LPS,', whereas, no, individual, element, is, absolutely, essential, for, cAMP, signaling])]). relacion([sujeto(['Induction', of, the, 'AP-1,', 'NF-IL-6,', and, 'NF-kappaB', elements, by, cAMP, is, correlated, with, the, appearance, of, inducible, factors]), verbo([binding]), complemento([to, these, 'sites,', whereas, factors, binding, to, the, 'MRE', are, constitutively, expressed])]). relacion([sujeto(['Our', results]), verbo([suggest]), complemento([that, cAMP, and, prostaglandins, act, through, 'multiple,', partially, 'redundant,', regulatory, elements, to, induce, 'IL-6', expression, in, monocytic, cells])]). relacion([sujeto(['The', mechanism, by, which]), verbo([activated]), complemento([ras, oncogene, expression, leads, to, repression, of, genes, encoding, specific, actin, filament, proteins, is, not, understood])]). relacion([sujeto(['However,', these, changes]), verbo([associated]), complemento([with, loss, of, organized, actin, 'filaments,', are, necessary, to, maintain, the, transformed, phenotype])]). relacion([sujeto(['In', this, 'study,', we, demonstrate, that, two, serum, response, elements, '(', 'SREs)', present, in, the, 'alpha-actin', promoter, are]), verbo([required]), complemento([for, transcriptional, repression, in, 'ras-transformed', cells, and, the, two, 'SREs', act, synergistically, to, repress, heterologous, promoters, in, a, 'ras-transformation', dependent, manner])]). relacion([sujeto(['Serum', response, factor, '(', 'SRF),', which, can]), verbo([bind]), complemento([to, the, sm, 'alpha-actin', 'SREs,', restores, 'alpha-actin', promoter, activity, in, 'ras-transformed', cells])]). relacion([sujeto(['c-Fos,', 'c-Jun', and, 'YY1', also, repress, 'alpha-actin', promoter, through, 'SREs,']), verbo([suggesting]), complemento([that, these, transcription, factors, may, play, a, role, in, repressing, 'alpha-actin', promoter, in, 'ras-transformed', cells])]). relacion([sujeto(['YY1', is, a, zinc, finger, transcription, factor, which]), verbo([acts]), complemento([as, either, a, repressor, or, an, activator, dependent, on, the, promoter, context])]). relacion([sujeto(['The']), verbo([activating]), complemento([activity, of, 'YY1', is, dependent, on, the, presence, of, a, newly, identified, switch, region, located, upstream, of, the, 'YY1', binding, site])]). relacion([sujeto(['Deletion', of, this, region]), verbo([causes]), complemento(['YY1', to, act, as, a, repressor, of, 'HPV-18', promoter, activity])]). relacion([sujeto(['In', vivo, footprinting, of, the, 'HPV-18', 'URR', and, an, in, vitro, electrophoretic, mobility, shift, assay, identified, proteins]), verbo([binding]), complemento([to, the, switch, region])]). relacion([sujeto(['Site-directed', mutagenesis, of, the, switch, region, and, 'YY1']), verbo([binding]), complemento([sites, suggests, that, these, two, regions, work, in, concert, to, yield, 'high-level', 'HPV-18', 'URR', activity, in, 'HeLa', cells, but, not, in, 'HepG2', 'cells,', where, 'HPV-18', is, almost, inactive])]). relacion([sujeto(['These', data, identified, a, novel, mode, of, cell, 'type-specific', regulation, of, 'HPV-18', promoter, activity, by, positive, or, negative, action, of, 'YY1,', determined, by, the, switch, region]), verbo([binding]), complemento(['factor(s)'])]). relacion([sujeto(['The', 'UCRBP', '(', 'YY1,', 'delta,', 'NF-E1)', protein]), verbo([has]), complemento([been, isolated, for, its, ability, to, bind, to, the, 'UCR', '(', upstream, conserved, 'region)', site, present, in, the, conserved, murine, leukemia, virus, long, terminal, repeat])]). relacion([sujeto(['The', present, study]), verbo([reveals]), complemento([the, following, 'results:', '(', 'i)', 'The', 'UCR', site, is, present, in, the, upstream, 'and/or', regulatory, regions, of, numerous, mammalian, cellular, and, viral, genes, to, which, both, recombinant, and, cellular, 'UCRBP', bind])]). relacion([sujeto(['UCR', sites, are, also]), verbo([found]), complemento([in, the, regulatory, regions, of, repetitive, sequences, including, human, 'LINE-1', elements, and, mouse, 'intracisternal-A', particle, sequences])]). relacion([sujeto(['(', 'ii)', 'By', immunological, and, 'UV', 'cross-linking', 'experiments,', we]), verbo([found]), complemento([that, two, 'proteins,', of, approx])]). relacion([sujeto(['(', 'iii)', 'There', is, evidence, that, 'UCRBP']), verbo([acts]), complemento([as, a, phosphoprotein])]). relacion([sujeto(['Eight', consensus, phosphorylation, sites, are]), verbo([found]), complemento([in, the, deduced, 'amino-acid', sequence, of, human, 'UCRBP'])]). relacion([sujeto(['The', cellular, 'UCR-binding', activity, was, abolished, by, phosphatase, 'treatment,', and, there, is, an, incremental]), verbo([increase]), complemento([in, apparent, molecular, mass, between, the, cytoplasmic, and, nuclear, forms, of, the, 'protein,', suggesting, phosphorylation])]). relacion([sujeto(['(', 'iv)', 'Although', 'UCRBP']), verbo([has]), complemento([been, previously, shown, to, act, as, a, transcriptional, 'repressor,', we, show, here, that, 'UCRBP', can, also, act, as, a, positive, transactivator, of, a, reporter, driven, by, 'UCR', elements, when, used, in, 'co-transfection', assays])]). relacion([sujeto(['(', 'ABSTRACT', 'TRUNCATED', 'AT', 250, 'WORDS)', 'Induction', of, 'interleukin-6', '(', 'IL-6)', gene, expression, is]), verbo([mediated]), complemento([by, numerous, agents, involving, all, major, signal, transduction, pathways])]). relacion([sujeto(['We']), verbo([have]), complemento([compared, the, effects, of, prostaglandins, and, their, second, messenger, cyclic, 'AMP', '(', 'cAMP)', with, the, effect, of, lipopolysaccharide, '(', 'LPS)', on, 'IL-6', gene, expression])]). relacion([sujeto(['We', demonstrate, that, secretion, of, 'IL-6', is]), verbo([induced]), complemento([by, cAMP, in, murine, monocytic, 'PU5-1'])]). relacion([sujeto(['Nevertheless,', cAMP, and, prostaglandins, of, the, 'E', series, in, the, presence, of, theophylline]), verbo([induce]), complemento([transcription, of, the, 'IL-6', promoter, more, strongly, than, 'LPS,', suggesting, distinctive, effects, of, cAMP, and, 'LPS', on, posttranscriptional, events])]). relacion([sujeto(['Mutations', within, four, regulatory, 'elements,', 'namely,', the, multiple, response, element, '(', 'MRE),', 'AP-1,', 'NF-IL6,', and, 'NF-kappa', 'B', 'sites,', significantly, 'reduce,', but, do, not, completely, 'abrogate,', inducibility, by, cAMP, and, prostaglandin, 'E1,', whereas, alterations, of, four, additional, sites]), verbo([have]), complemento([no, effects])]). relacion([sujeto(['LPS-induced', promoter, 'activity,', 'however,', is, almost, completely, abolished, by, mutations, in, the, 'NF-kappa', 'B', 'site,']), verbo([suggesting]), complemento([that, a, single, regulatory, element, is, crucial, for, inducibility, by, 'LPS'])]). relacion([sujeto(['Stimulation', by, cAMP, is, correlated, with, the]), verbo([binding]), complemento([of, inducible, factors, to, the, 'AP-1,', 'NF-IL6,', and, 'NF-kappa', 'B', 'elements,', whereas, factors, binding, to, the, 'MRE', are, constitutively, expressed])]). relacion([sujeto(['Recombinant', cAMP, response, 'element-binding', protein]), verbo([binds]), complemento([to, the, 'MRE,', indicating, a, potential, role, for, this, factor, in, the, cAMP, response])]). relacion([sujeto(['Our', results]), verbo([suggest]), complemento([that, cAMP, and, prostaglandins, act, through, 'multiple,', partially, redundant, regulatory, elements, to, induce, 'IL-6', expression, in, monocytic, cells])]). relacion([sujeto(['We', present, evidence, that, this, incompatibility, can, be]), verbo([caused]), complemento([in, part, by, the, dual, activity, of, a, 'Kruppel-related', zinc, 'finger,', 'YY1', '(', formerly, 'F-ACT1),', in, differentially, regulating, oncogene, and, 'muscle-specific', gene, expression])]). relacion([sujeto(['The', 'c-myc', and, skeletal, 'alpha-actin', gene, promoters, contain, 'YY1']), verbo([binding]), complemento([sites, thought, to, act, either, as, positive, or, negative, 'cis-acting', elements])]). relacion([sujeto(['Through', manipulating, the, intracellular, level, of, 'YY1', by, treating, primary, myoblasts, with, bromodeoxyuridine, '(', 'BrdU),', which]), verbo([inhibited]), complemento([myogenesis, and, increased, the, 'YY1', protein, 'content,', or, by, transfecting, 'YY1', cDNA, expression, 'vector,', we, show, that, it, can, simultaneously, inhibit, and, activate, expression, of, the, skeletal, 'alpha-actin', and, 'c-myc', 'genes,', respectively])]). relacion([sujeto(['The', transrepression, activity, of, 'YY1', solely, depends, on, its, 'C-terminal', zinc, finger, region, '(', amino, acids, 297, -, 407, ')', while, its, transactivation, function]), verbo([requires]), complemento([an, additional, 'N-terminal', domain, '(', amino, acids, 1, -, 90, ')', normally, masked, in, the, 'full-length', protein])]). relacion([sujeto(['We', propose, that, the, high, level, of, 'YY1', in, proliferating, myoblasts, might, serve, to]), verbo([maintain]), complemento(['c-myc', expression, and, suppress, muscle, actin, 'expression,', which, can, then, be, gradually, reversed, by, downregulating, 'YY1', activity, toward, myogenesis])]). relacion([sujeto(['The', 'macrophage-derived', cytokine, 'interleukin-1', '(', 'IL-1)', can]), verbo([provide]), complemento([a, second, signal, with, antigen, to, elicit, production, of, 'interleukin-2', '(', 'IL-2)', by, helper, 'T', cells])]). relacion([sujeto(['The', 'pathway(s)']), verbo([involved]), complemento([remains, 'controversial,', with, protein, kinase, 'C', and, cyclic, 'AMP', '(', 'cAMP)', invoked, as, possible, second, messengers])]). relacion([sujeto(['E1,', 'IL-1', could, synergize, with, the, phosphoinositide, 'pathway,', because, the, cells, made, higher, levels, of, 'IL-2', in, the, presence, of, 'IL-1', than, could, be]), verbo([induced]), complemento([by, phorbol, ester, plus, calcium, ionophore, alone])]). relacion([sujeto(['IL-1', is, unlikely, to]), verbo([act]), complemento([through, a, sustained, increase, in, cAMP, in, these, cells, because, it, did, not, raise, cAMP, levels, detectably, and, because, 'IL-1', and, forskolin, had, opposite, effects, on, 'IL-2', gene, expression])]). relacion([sujeto(['Inducible', expression, of, a, transfected, reporter, gene, linked, to, a, cloned, fragment, of, the, murine, 'IL-2', gene, promoter, was, initially]), verbo([increased]), complemento([by, 'IL-1', 'costimulation,', implying, that, 'IL-1', can, increase, the, rate, of, transcription, of, 'IL-2'])]). relacion([sujeto(['The', minimal, promoter, elements]), verbo([required]), complemento([for, 'iL-1', responsiveness, were, located, within, 321, bp, of, the, 'IL-2', 'RNA', cap, 'site,', and, further, upstream, sequences, to, -, 2800, did, not, modify, this, response])]). relacion([sujeto(['IL-1', costimulation, resulted, in]), verbo([enhanced]), complemento([activity, of, both, an, inducible, 'NF-kappa', 'B-like', factor, and, one, of, two, distinct, 'AP-1-like', factors, that, bind, to, 'IL-2', regulatory, sequences])]). relacion([sujeto(['Another', 'AP-1-like', factor, and, 'NFAT-1,', while, inducible, in, other, cell, 'types,', were]), verbo([expressed]), complemento([constitutively, in, the, 'EL4'])]). relacion([sujeto(['The', results, presented, demonstrate, that, exposures, to, the, 'Nrf2', 'activators,', sulforaphane, '(', 'SFN)', and, 'tert-butylhydroquinone', '(', 'tBHQ),', markedly]), verbo([activate]), complemento(['E1b', transcription, in, human, lung, and, liver, cells])]). relacion([sujeto(['In', 'BEAS-2B', 'cells,', the, 'Nrf2', 'effectors,', 'SFN', and, 'tBHQ,', selectively]), verbo([activated]), complemento([the, more, distal, 'HS-2', through, an, antioxidant, response, element, '(', 'ARE)'])]). relacion([sujeto(['The', results, demonstrate, that, 'ARE', 'modulation,', integrated, with, additional, transcriptional, 'complexes,']), verbo([regulates]), complemento([the, 'tissue-specific', expression, of, mEH, and, that, these, processes, likely, coordinate, both, the, protective, and, bioactivation, functions, contributed, by, mEH, activities, in, human, tissues])]). relacion([sujeto(['The', pluripotent, 'P19', embryo, carcinoma, cell, line, was, studied, to, determine, a, signaling, pathway]), verbo([regulating]), complemento(['MeCP2', expression])]). relacion([sujeto(['P19', cells, were]), verbo([induced]), complemento([to, differentiate, into, neurons, by, 'RA', and, express, 'β-III', tubulin, at, one, day, after, induction, and, synaptophysin, by, 7, days])]). relacion([sujeto(['Both', 'Mecp2', e1, and, e2, mRNA, forms, progressively]), verbo([increased]), complemento([in, differentiating, cells])]). relacion([sujeto(['MeCP2', expression, was]), verbo([increased]), complemento([by, tumor, necrosis, factor, '(', 'TNF)', in, early, differentiating, 'cells,', which, was, blocked, by, 'NFκB', inhibitors])]). relacion([sujeto(['TNF', did, not]), verbo([increase]), complemento(['MeCP2', expression, in, naïve, cells])]). relacion([sujeto(['Moreover,', 'TNF', did, not]), verbo([increase]), complemento(['NFκB', reporter, gene, activity, in, naïve, cells, even, though, increases, were, observed, in, early, differentiating, cells])]). relacion([sujeto(['The', protein, kinase, 'C', activator, phorbol, 12, -, myristate, 13, -, acetate, '(', 'PMA)']), verbo([increased]), complemento(['MeCP2', expression, in, naïve, 'P19', 'cells,', which, was, also, blocked, by, 'NFκB', inhibitors])]). relacion([sujeto(['Interestingly,', 'PMA']), verbo([increased]), complemento(['NFκB', reporter, gene, activity, in, naïve, cells])]). relacion([sujeto(['Finally,', 'PMA,', but, not, 'TNF,']), verbo([induced]), complemento(['IκBα', degradation, in, naïve, 'P19', cells])]). relacion([sujeto(['Taken', 'together,', our, data, indicates, that, 'MeCP2', expression, is]), verbo([regulated]), complemento([in, part, by, signaling, pathways, involving, 'NFκB'])]). relacion([sujeto(['The', expression, of, 'RANKL', by, immune, cells, may, contribute, to, bone]), verbo([loss]), complemento([in, 'periodontitis,', 'arthritis,', and, multiple, myeloma])]). relacion([sujeto(['A', recent, discovery]), verbo([reveals]), complemento([that, 'DCs', release, the, chromatin, protein, high, mobility, group, box, 1, '(', 'HMGB1)', as, a, potent, immunomodulatory, cytokine, mediating, the, interaction, between, 'DCs', and, 'T-cells,', via, 'HMGB1', binding, to, the, membrane, receptor, for, advanced, glycation, end, products, '(', 'RAGE)'])]). relacion([sujeto(['To', determine, whether, osteoblasts, or, osteoclasts]), verbo([express]), complemento(['and/or', release, 'HMGB1', into, the, bone, 'microenvironment,', we, analyzed, 'tissue,', 'cells,', and, culture, media, for, the, presence, of, this, molecule])]). relacion([sujeto(['Our', immunohistochemical, and, immunocytochemical, analyses, demonstrate, 'HMGB1', expression, in, primary, osteoblasts, and, osteoclasts, and, that, both, cells]), verbo([express]), complemento(['RAGE'])]). relacion([sujeto(['Parathyroid', hormone, '(', 'PTH),', a, regulator, of, bone, 'remodeling,', attenuates, 'HMGB1']), verbo([release]), complemento([in, cultures, of, primary, osteoblasts, and, 'MC3T3-E1', 'osteoblast-like', cells, but, augments, this, release, in, the, rat, osteosarcoma, cell, line, 'UMR', 106, -, 1, ',', both, responses, primarily, via, activation, of, adenylyl, cyclase])]). relacion([sujeto(['PTH-induced', 'HMGB1', discharge, by, 'UMR', cells, exhibits, similar]), verbo([release]), complemento([kinetics, as, reported, for, activated, macrophages])]). relacion([sujeto(['Principally']), verbo([expressed]), complemento([on, the, surface, of, 'T', 'lymphocytes,', the, chemokine, and, 'HIV', receptor, 'CXCR4', has, been, shown, to, serve, key, roles, in, both, chemotaxis, and, 'HIV-1-entry', into, 'T', cells])]). relacion([sujeto(['Using', an, 'RNase', protection, assay, '(', 'RPA),', we]), verbo([have]), complemento([demonstrated, that, mitogenic, stimulation, of, purified, human, peripheral, blood, 'T', lymphocytes, '(', 'PBL)', decreased, 'CXCR4', mRNA, relative, to, unstimulated, controls, in, a, 'calcineurin-dependent', 'manner;', an, expression, pattern, mimicked, by, the, chemokine, receptor, 'CCR7'])]). relacion([sujeto(['A', change, in, transcriptional, 'activity,', not, in, mRNA, 'stability,', was]), verbo([required]), complemento([for, control, of, 'CXCR4', and, 'CCR7', expression])]). relacion([sujeto(['Changes', in, 'CXCR4', mRNA, expression]), verbo([translated]), complemento([into, a, 'stimulation-', and, 'calcineurin-dependent', decrease, in, cell, surface, 'CXCR4', expression])]). relacion([sujeto(['We']), verbo([have]), complemento([previously, demonstrated, that, 'CXCR4', mRNA, and, protein, is, regulated, by, 'cAMP;', here, we, show, that, calcium, and, calcineurin, signaling, pathways, modify, 'cAMP-driven', changes])]). relacion([sujeto(['Moreover,', we]), verbo([provide]), complemento([data, supporting, a, role, for, the, transcription, factor, 'YY1', in, 'calcineurin-dependent', regulation, of, 'CXCR4', expression])]). relacion([sujeto(['Multiple', signal, transduction, pathways, are, generally]), verbo([triggered]), complemento([simultaneously, by, a, single, extracellular, stimulus])]). relacion([sujeto(['As', a, 'result,', multiple, transcription, factors, '(', 'TFs)', can, be]), verbo([activated]), complemento([downstream, to, mediate, the, inducible, expression, of, target, genes])]). relacion([sujeto(['Tumor', necrosis, factor, alpha, '(', 'TNFalpha)', and, phorbol, 12, -, myristate, 13, -, acetate, '(', 'PMA)']), verbo([mediate]), complemento([many, biological, 'functions,', including, cell, proliferation, and, 'apoptosis,', by, stimulating, signaling, pathways])]). relacion([sujeto(['Two', 'TFs,']), verbo([nuclear]), complemento([factor, kappaB, '(', 'NFkappaB)', and, activating, factor, 1, '(', 'AP1),', have, been, identified, as, targets, of, both, 'TNFalpha', and, 'PMA', activation])]). relacion([sujeto(['Here,', we, describe, the, use, of, a, 'protein/DNA', array, system, to, identify, additional, 'TFs']), verbo([activated]), complemento([by, 'TNFalpha', and, 'PMA', in, 'HeLa', cells])]). relacion([sujeto(['From', a, total, of, 150]), verbo([targeted]), complemento(['TFs,', 'six-CREB,', 'E2F,', 'CETP/CRE,', 'c-Rel,', 'MSP1,', and, 'Pax6-were', identified, whose, 'activities,', like, 'NFkappaB', and, 'AP1,', were, regulated, by, both, 'TNFalpha-', and, 'PMA-induced', pathways])]). relacion([sujeto(['Interestingly,', the, 'TF', 'E47', was, shown, to, be, specifically]), verbo([activated]), complemento([by, 'TNFalpha', but, was, not, affected, by, treatment, with, 'PMA'])]). relacion([sujeto(['In', 'addition,', 'GATA,', 'NF-E1,', and, 'ISRE', were, shown, to, be, specifically]), verbo([activated]), complemento([by, 'PMA', but, not, 'TNFalpha'])]). relacion([sujeto(['These', findings]), verbo([suggest]), complemento([that, 'TNFalpha', and, 'PMA', both, stimulate, unique, signaling, pathways, while, mediating, transcriptional, activation, through, common, pathways])]). relacion([sujeto(['Histone', acetylation, alters, the, chromatin, structure, and]), verbo([activates]), complemento([the, genes, that, are, repressed, by, histone, deacetylation])]). relacion([sujeto(['This', investigation, demonstrates, that, treating, 'P3HR1', cells, with, trichostatin, 'A', '(', 'TSA)']), verbo([activates]), complemento([the, 'Epstein-Barr', virus, '(', 'EBV)', lytic, 'cycle,', allowing, the, virus, to, synthesize, three, viral, lytic, 'proteins-Rta,', 'Zta', and, 'EA-D'])]). relacion([sujeto(['Experimental', results, indicate, that, 'TSA', and, 12, -, 'O:-tetradecanoylphorbol-13-acetate', synergistically]), verbo([activate]), complemento([the, transcription, of, 'BRLF1,', an, 'immediate-early', gene, of, 'EBV'])]). relacion([sujeto(['Chromatin', immunoprecipitation, assay]), verbo([reveals]), complemento([that, histone, 'H4', at, the, 'BRLF1', promoter, is, acetylated, after, 'P3HR1', cells, are, treated, with, 'TSA,', suggesting, that, histone, acetylation, activates, 'BRLF1', transcription])]). relacion([sujeto(['Furthermore,', results, in, this, study, demonstrate, that, mutation, of, a, 'YY1-binding', site, in, the, 'BRLF1', promoter]), verbo([activates]), complemento(['BRLF1', transcription, 1.6, -, and, 2.3, -, fold, in, 'P3HR1', cells, and, 'C33A', 'cells,', respectively])]). relacion([sujeto(['Real', time, 'PCR', analysis]), verbo([reveals]), complemento([that, the, mutation, also, increases, the, histone, acetylation, level, of, the, nucleosomes, at, the, 'BRLF1', promoter, 1])]). relacion([sujeto(['Results', presented, herein]), verbo([suggest]), complemento([that, histone, deacetylation, plays, an, important, role, in, maintaining, the, viral, latency, and, histone, acetylation, at, the, 'BRLF1', promoter, allows, the, virus, to, express, 'Rta', and, to, activate, the, viral, lytic, cycle])]). relacion([sujeto(['The', phorbol, 'ester,', 12, -, 'O-tetradecanoylphorbol-13-acetate', '(', 'TPA),']), verbo([enhances]), complemento([transcription, of, many, eukaryotic, 'genes,', including, that, for, dopamine, 'beta-hydroxylase', '(', 'DBH)'])]). relacion([sujeto(['In', the, present, 'study,', we]), verbo([report]), complemento([identification, and, characterization, of, a, novel, sequence, motif, residing, in, the, 5, '\'', -, flanking, region, of, the, human, 'DBH', 'gene,', which, mediates, transcriptional, induction, by, 'TPA'])]). relacion([sujeto(['In', 'addition,', alteration, of, the, 'YY1-binding', site]), verbo([decreased]), complemento(['TPA-mediated', induction, of, the, 'DBH', promoter, 'activity,', suggesting, that, contiguous, 'cis-regulatory', 'element(s)', cooperate, with, this, novel, sequence, motif])]). relacion([sujeto(['Taken', 'together,', these, data]), verbo([suggest]), complemento([that, transcriptional, 'up-regulation', of, the, human, 'DBH', gene, in, response, to, 'TPA', requires, coordination, of, a, novel, 'TRE', '(', human, 'DBH', 'TRE,', 'hDTRE),', cyclic, 'AMP-responsive', 'element,', and, the, 'YY1-binding', site])]). relacion([sujeto(['Cytomegalovirus', '(', 'CMV)', infection, is, nonpermissive, or, persistent, in, many, lymphoid, and, myeloid, cell, types, but, can, be]), verbo([activated]), complemento([in, differentiated, macrophages])]). relacion([sujeto(['We']), verbo([have]), complemento([shown, elsewhere, that, both, the, major, 'immediate-early', gene, '(', 'MIE)', and, lytic, cycle, infectious, progeny, virus, expression, can, be, induced, in, otherwise, nonpermissive, 'monocyte-like', 'U-937', cell, cultures, infected, with, either, human, 'CMV', '(', 'HCMV)', or, simian, 'CMV', '(', 'SCMV)', by, treatment, with, the, phorbol, ester, 12, -, 'O-tetradecanoylphorbol-13-acetate', '(', 'TPA)'])]). relacion([sujeto(['Two', multicopy, basal, enhancer, motifs, within, the, 'SCMV', 'MIE', 'enhancer,', 'namely,', 11, copies, of, the, 16, -, bp, cyclic, 'AMP', response, element, '(', 'CRE)', and, 3, copies, of, novel, 17, -, bp, serum, response, factor, '(', 'SRF)']), verbo([binding]), complemento([sites, referred, to, as, the, 'SNE', '(', 'SRF/NFkappaB-like', 'element),', as, well, as, four, classical, 'NFkappaB', sites, within, the, 'HCMV', 'version,', contribute, to, 'TPA', responsiveness, in, transient, assays, in, monocyte, and, 'T-cell', types])]). relacion([sujeto(['The', 'SCMV', 'SNE', sites, contain, potential, overlapping, core, recognition]), verbo([binding]), complemento([motifs, for, 'SRF,', 'Rel/NFkappaB,', 'ETS,', and, 'YY1', class, transcription, factors, but, fail, to, respond, to, either, serum, or, tumor, necrosis, factor, alpha])]). relacion([sujeto(['Therefore,', to, evaluate, the, mechanism, of, 'TPA', responsiveness, of, the, 'SNE', motifs, and, of, a, related, 16, -, bp, 'SEE', '(', 'SRF/ETS', 'element)', motif]), verbo([found]), complemento([in, the, 'HCMV', and, chimpanzee, 'CMV', 'MIE', 'enhancers,', we, have, examined, the, functional, responses, and, protein, binding, properties, of, multimerized, 'wild-type', and, mutant, elements, added, upstream, to, the, 'SCMV', 'MIE', or, simian, virus, 40, minimal, promoter, regions, in, the, 'U-937,', 'K-562,', 'HL-60,', 'THP-1,', and, 'Jurkat', cell, lines])]). relacion([sujeto(['Unlike', classical, 'NFkappaB', 'sites,', neither, the, 'SNE', nor, the, 'SEE', motif]), verbo([responded]), complemento([to, phosphatase, inhibition, by, okadaic, acid])]). relacion([sujeto(['However,', the, 'TPA', responsiveness, of, both, 'CMV', elements, proved, to]), verbo([involve]), complemento([synergistic, interactions, between, the, core, 'SRF', binding, site, '(', 'CCATATATGG)', and, the, adjacent, inverted, 'ETS', binding, motifs, '(', 'TTCC),', which, correlated, directly, with, formation, of, a, bound, tripartite, complex, containing, both, the, cellular, 'SRF', and, 'ELK-1', proteins])]). relacion([sujeto(['This', protein, complex, was, more, abundant, in, 'U-937,', 'K-562,', and, 'HeLa', cell, extracts, than, in, 'Raji,', 'HF,', 'BALB/c', 3, 'T3,', or, 'HL-60', 'cells,', but, the]), verbo([binding]), complemento([activity, was, altered, only, twofold, after, 'TPA', treatment])]). relacion([sujeto(['A', 40, -, fold, stimulation, of, chloramphenicol, acetyltransferase, activity]), verbo([mediated]), complemento([by, four, tandem, repeats, of, the, 'SNE', could, be, induced, within, 2, h, '(', and, up, to, 250, -, fold, within, 6, 'h)', after, addition, of, 'TPA', in, 'DNA-transfected', 'U-937', 'cells,', indicating, that, the, stimulation, appeared, likely, to, be, a, true, protein, kinase, 'C-mediated', signal, transduction, event, rather, than, a, differentiation, response])]). relacion([sujeto(['Slight', differences, in, the, sequence, of, the, core, 'SRF']), verbo([binding]), complemento([site, compared, with, that, of, the, classical, 'c-Fos', promoter, serum, response, 'element,', together, with, differences, in, the, spacing, between, the, 'SRF', and, 'ETS', 'motifs,', appear, to, account, for, the, inability, of, the, 'SCMV', 'SNEs', to, respond, to, serum, induction])]). relacion([sujeto(['A', 48, -, bp, 'cis-acting', negative, element, in, the, 'Epstein-Barr', virus, 'BZLF1', gene, 'P1', promoter]), verbo([has]), complemento([been, described, previously])]). relacion([sujeto(['In', this, 'report,', the, cellular, transcription, factor, 'YY1']), verbo([has]), complemento([been, identified, as, a, protein, which, binds, to, both, of, these, 'elements,', now, designated, 'ZIVA', and, 'ZIVB'])]). relacion([sujeto(['Both', 'ZIVA', and, 'ZIVB']), verbo([conferred]), complemento(['cis-acting', negative, regulation, on, an, enhancerless, simian, virus, 40, promoter])]). relacion([sujeto(['In', cotransfection, 'experiments,', overexpression, of, 'YY1']), verbo([caused]), complemento([further, repression, of, the, enhancerless, simian, virus, 40, promoter, containing, either, the, 'ZIVA', or, 'ZIVB', element])]). relacion([sujeto(['Cotransfection', of, a, plasmid]), verbo([expressing]), complemento([antisense, to, 'YY1', increased, the, expression, of, the, heterologous, promoter, containing, 'ZIVA', but, not, 'ZIVB'])]). relacion([sujeto(['In', similar, experiments, carried, out, with, the, 'P1', 'promoter,', overexpression, of, 'YY1']), verbo([caused]), complemento([downregulation, of, 'P1', whereas, antisense, 'RNA', to, 'YY1', caused, a, slight, increase, in, expression])]). relacion([sujeto(['Overexpression', of, 'YY1', also]), verbo([caused]), complemento([downregulation, of, a, 'P1', mutant, with, no, apparent, 'YY1-binding', sites])]). relacion([sujeto(['TPA', treatment, of, 'Raji', cells]), verbo([caused]), complemento([a, temporal, loss, of, 'YY1-binding', activity, but, had, no, effect, on, the, intracellular, levels, of, 'YY1', protein])]). relacion([sujeto(['Serum', induction, of, quiescent, 'B', cells, also]), verbo([caused]), complemento([loss, of, 'YY1', binding, to, the, 'ZIVB', 'site,', which, was, found, to, be, a, weak, serum, response, element])]). relacion([sujeto(['The']), verbo([binding]), complemento([of, 'YY1', to, the, 'cis-acting', negative, elements, in, infected, 'B', cells, may, play, a, pivotal, role, in, the, maintenance, of, 'Epstein-Barr', virus, latency])]). relacion([sujeto(['Elevation', of, cAMP, can]), verbo([cause]), complemento(['gene-specific', inhibition, of, interleukin, 2, '(', 'IL-2)', expression])]). relacion([sujeto(['To', investigate, the, mechanism, of, this, 'effect,', we]), verbo([have]), complemento([combined, electrophoretic, mobility, shift, assays, and, in, vivo, genomic, footprinting, to, assess, both, the, availability, of, putative, 'IL-2', transcription, factors, in, 'forskolin-treated', cells, and, the, functional, capacity, of, these, factors, to, engage, their, sites, in, vivo])]). relacion([sujeto(['E1', cell, 'line,', we]), verbo([report]), complemento([specific, inhibitory, effects, of, cAMP, elevation, both, on, 'NF-kappa', 'B/Rel', family, factors, binding, at, -, 200, 'bp,', and, on, a, 'novel,', biochemically, distinct, &, 'quot;TGGGC"', factor, binding, at, -, 225, bp, with, respect, to, the, 'IL-2', transcriptional, start, site])]). relacion([sujeto(['Neither', 'NF-AT', nor, 'AP-1']), verbo([binding]), complemento([activities, are, detectably, inhibited, in, gel, mobility, shift, assays])]). relacion([sujeto(['Elevation', of, cAMP]), verbo([inhibits]), complemento(['NF-kappa', 'B', activity, with, delayed, kinetics, in, association, with, a, delayed, inhibition, of, 'IL-2', 'RNA', accumulation])]). relacion([sujeto(['Activation', of, cells, in, the, presence, of, forskolin]), verbo([prevents]), complemento([the, maintenance, of, stable, 'protein-DNA', interactions, in, 'vivo,', not, only, at, the, 'NF-kappa', 'B', and, 'TGGGC', sites, of, the, 'IL-2', 'enhancer,', but, also, at, the, 'NF-AT,', 'AP-1,', and, other, sites])]). relacion([sujeto(['This', 'result,', and, similar, results, in, cyclosporin, 'A-treated', 'cells,', imply, that, individual, 'IL-2', transcription, factors, cannot, stably]), verbo([bind]), complemento([their, target, sequences, in, vivo, without, coengagement, of, all, other, distinct, factors, at, neighboring, sites])]). relacion([sujeto(['It', is, proposed, that, 'nonhierarchical,', cooperative, enhancement, of]), verbo([binding]), complemento([is, a, structural, basis, of, combinatorial, transcription, factor, action, at, the, 'IL-2', locus])]). relacion([sujeto(['The', human, papillomavirus, type, 18, '(', 'HPV-18)', promoter, contains, a, 'TPA', responsive, element, '(', 'TRE)', which]), verbo([confers]), complemento(['TPA', responsiveness, on, a, heterologous, promoter])]). relacion([sujeto(['We']), verbo([have]), complemento([identified, a, negative, regulatory, domain, in, the, 'HPV-18', promoter, which, represses, the, constitutive, and, 'TPA-induced', 'AP-1', activity])]). relacion([sujeto(['This', negative, regulatory, sequence]), verbo([has]), complemento([been, mapped, to, 44, nucleotides, '(', 'OL13)'])]). relacion([sujeto(['The', transcriptional, repressor, protein, 'YY1,', which, negatively]), verbo([regulates]), complemento([the, 'P5', 'promoter,', binds, to, the, 'HPV-18', silencer, with, high, affinity])]). relacion([sujeto(['Mutation', of, the, 'YY1']), verbo([binding]), complemento([site, leads, to, an, enhanced, activity, of, the, 'HPV-18', 'promoter,', strongly, suggesting, that, 'YY1', plays, an, important, role, in, controlling, 'HPV-18', early, gene, expression])]). relacion([sujeto(['We']), verbo([have]), complemento([studied, the, elements, involved, in, the, tetradecanoylphorbol, acetate, '(', 'TPA)-mediated', extinction, of, 'erythroid-specific', genes])]). relacion([sujeto(['Examination', of, the, 'DNA']), verbo([binding]), complemento([activity, of, 'trans-acting', factors, involved, in, the, expression, of, the, porphobilinogen, deaminase, erythroid, promoter, showed, '(', 'i)', a, constitutive, expression, of, the, 'CACC', binding, proteins, and, '(', 'ii)', a, decrease, in, 'DNA', binding, activity, of, two, 'tissue-specific', 'factors,', 'NF-E1', and, 'NF-E2'])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, different, 'pathways,', acting, via, different, transcription, 'factors,', are, involved, in, the, 'TPA-mediated', extinction, of, 'erythroid-specific', genes])]). relacion([sujeto(['ALP', activity, was, significantly]), verbo([decreased]), complemento([in, 'TNF-α', 'group,', group, 'B', and, group, 'C', compared, with, control, 'group(P<0'])]). relacion([sujeto(['The', protein, levels, of, 'BMP-2,', 'RUNX2', and, 'Osterix', were, significantly]), verbo([decreased]), complemento([in, 'TNF-α', 'group,', group, 'B', and, group, 'C', compared, with, control, 'group(P<0'])]). relacion([sujeto(['Protein', level, of, 'RANKL', was, significantly]), verbo([increased]), complemento([in, 'TNF-α', 'group,', grope, 'B', and, group, 'C', compared, with, control, 'group(P<0'])]). relacion([sujeto(['The', concentration, of, 10, '(', -, 4, ')', 'mol/L', 'Zn(2+)', can, significantly]), verbo([increase]), complemento([the, expression, of, osteoblastic, proteins, such, as, 'ALP,', 'BMP-2,', 'RUNX2,', 'Osterix', and, decrease, the, expression, of, 'RANKL', in, mice, osteoblasts, in, 'TNF-α', inflammatory, environment])]). relacion([sujeto(['However,', the, formation, of, 'ROS', on, the, titanium, surfaces, might]), verbo([have]), complemento([negative, response, of, the, activity, of, the, surroundings, cells])]). relacion([sujeto([20135, and]), verbo([found]), complemento([to, reduce, the, effects, of, 'LPS-induced', inflammation])]). relacion([sujeto(['The', cells, on, the, titanium, surface, produced, excessive, 'ROS', and]), verbo([decreased]), complemento([the, activity, of, 'Cu/Zn', 'SOD', and, 'Mn', 'SOD'])]). relacion([sujeto(['In', 'addition,', 'MC-3T3', 'E1', 'osteoblast-like', cells]), verbo([promoted]), complemento([osteoclast, differentiation, but, reduced, osteoblast, differentiation, and, mineralization, on, the, titanium, surface])]). relacion([sujeto(['Moreover,', 'Terrein']), verbo([promoted]), complemento([osteoblast, differentiation, and, bone, mineralization, to, elevate, the, activity, of, 'ALP,', 'SPARC', and, 'down-regulate', 'RANKL', expression, after, blocking, 'NF-κB', translocation, from, the, cytosol, to, the, nucleus])]). relacion([sujeto(['In', 'conclusion,', the, presence, of, 'Terrein', on, titanium, surfaces]), verbo([increases]), complemento([osteoblast, cell, growth, without, inflammation])]). relacion([sujeto(['Moreover,', 'Terrein,', as, a, putative, antioxidant, 'agent,', may]), verbo([enhance]), complemento([osseointegration, by, decreasing, the, level, of, 'ROS', and, having, a, potentially, synergistic, effect, on, osteoblast, differentiation])]). relacion([sujeto(['CTCF', is, a]), verbo([nuclear]), complemento([phosphoprotein, capable, of, using, different, subsets, of, its, 11, 'Zn', fingers, '(', 'ZF)', for, 'sequence-specific', binding, to, many, dissimilar, 'DNA', 'CTCF-target', sites])]). relacion([sujeto(['CTCF/DNA-complexes', formed, in, vivo, with, different, 50, -, 'bp-long', sequences]), verbo([mediate]), complemento([diverse, functions, such, as, positive, and, negative, regulation, of, 'promoters,', and, organization, of, all, known, 'enhancer-blocking', elements, '(', &, 'quot;chromatin', 'insulators")', including, constitutive, and, epigenetically, regulated, elements])]). relacion([sujeto(['Transfection', assays, with, luciferase, 'reporter-constructs', identified, a, core, promoter, region, within, 146, bp, immediately, upstream, of, the, transcriptional, start, site, of, zebrafish, 'CTCF', that, is, located, at, a, highly]), verbo([conserved]), complemento(['YY1/Initiator', element])]). relacion([sujeto(['The', preferential, screening, of, cDNA, libraries, derived, from, the, mouse, osteoblastic, cell, line, 'MC3T3-E1']), verbo([has]), complemento([yielded, a, cDNA, clone, encoding, a, 442, -, 'amino-acid', protein, designated, 'STAP', '(', signal, transduction, and, adaptor, 'protein),', which, contains, several, motifs, shared, among, transcription, factors, and, adaptors, such, as, a, 'Zn-finger', like, 'motif,', a, 'proline-rich', 'domain,', and, a, 'PEST', sequence])]). relacion([sujeto(['The', amino, acid, sequence, homology, search, also]), verbo([reveals]), complemento([that, 'STAP', is, identical, to, a, mouse, oxidative, stress, 'protein,', 'A170,', and, has, 90, '%', homology, with, a, human, p62, protein, that, binds, to, the, tyrosine, kinase, 'p56(lck)', 'SH2', domain])]). relacion([sujeto(['In', 'MC3T3-E1', 'cells,', 'STAP', mRNA, was]), verbo([induced]), complemento([by, treatment, with, 'TGF-beta,', but, not, with, 'BMP-2', or, 'GDF-5'])]). relacion([sujeto(['The', transcription, start, site, was, identified, by]), verbo([primer]), complemento([extension, analysis, to, be, located, 35, bp, upstream, from, the, translation, initiation, site])]). relacion([sujeto(['Sequencing', analysis, of, the, 5, '\'', flanking, region, of, the, 'STAP', gene, revealed, multiple, consensus, 'motifs/sequences', for, several, 'DNA']), verbo([binding]), complemento([transcription, factors])]). relacion([sujeto(['Potential', 'Sp1,', 'AP-1,', 'NF-E2,', 'MyoD,', and, 'NF-kappaB']), verbo([binding]), complemento([sites, were, found, in, the, 5, '\'', flanking, region, '(', 1.4, 'kb)', of, the, 'STAP', gene])]). relacion([sujeto(['We']), verbo([have]), complemento([identified, a, new, 'Zn', finger, 'protein,', 'RYBP,', which, interacts, directly, with, both, 'Ring1', proteins, '(', 'Ring1A', and, 'Ring1B)', and, with, 'M33,', two, mutually, interacting, sets, of, proteins, of, the, mammalian, 'Polycomb', complex])]). relacion([sujeto(['Ring1']), verbo([binds]), complemento(['RYBP', and, 'M33', through, the, same, 'C-terminal', 'domain,', whereas, the, 'RYBP-M33', interaction, takes, place, through, an, 'M33', domain, not, involved, in, 'Ring1', binding])]). relacion([sujeto(['RYBP', also]), verbo([interacts]), complemento([directly, with, 'YY1,', a, transcription, factor, partially, related, to, the, product, of, the, 'Drosophila', pleiohomeotic, gene])]). relacion([sujeto(['In', 'addition,', we, show, here, that, 'RYBP']), verbo([acts]), complemento([as, a, transcriptional, repressor, in, transiently, transfected, cells])]). relacion([sujeto(['Taken', 'together,', these, data]), verbo([suggest]), complemento([that, 'RYBP', may, play, a, relevant, role, in, 'PcG', function, in, mammals])]). relacion([sujeto(['Using', an, 'electrophoretic-mobility-shift', assay, and, a, supershift, assay, with, a, specific, 'antibody,', the, 'cis-elements', of, the, 'PRE', and, 'NRE', were, identified, as]), verbo([binding]), complemento([sites, for, transcription, factors, 'Elk1', and, 'YY1', '(', 'Ying-Yang', 1, ')', respectively])]). relacion([sujeto(['Consistent', with, the, presumed, roles, of, the, 'PRE', and, 'NRE,', 'Elk1']), verbo([increased]), complemento(['SOD1', gene, transcription, about, 4, -, 5, -, 'fold,', whereas, 'YY1', exerted, a, negative, effect, of, about, 6, -, fold])]). relacion([sujeto(['Mutations', of, the, 'Elk1-', and, 'YY1-binding', sites]), verbo([led]), complemento([to, diminution, and, elevation, respectively, of, transcriptional, 'activities,', both, in, the, natural, context, and, in, heterologous, promoter, systems])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, the, transcription, factors, 'Elk1', and, 'YY1,', binding, in, the, 'PRE', and, 'NRE', 'respectively,', 'co-ordinate', the, expression, of, the, 'SOD1', gene])]). relacion([sujeto(['Yy2']), verbo([has]), complemento([been, treated, as, a, largely, immaterial, duplication, of, 'Yy1,', as, they, share, high, homology, in, the, 'Zinc', 'Finger-region', and, similar, if, not, identical, in, vitro, binding, sites])]). relacion([sujeto(['Moreover,', the, chromatin]), verbo([binding]), complemento([sites, for, 'YY2,', except, for, its, association, with, transposable, retroviral, elements, '(', 'RE)', and, 'Endogenous', 'Retroviral', 'Elements', '(', 'ERVs),', remain, to, be, identified])]). relacion([sujeto(['As', a, first, step, towards, defining, potential, 'Yy2', functions, matching, or, complementary, to, 'Yy1,', we, considered, in, vivo, 'DNA']), verbo([binding]), complemento([sites, of, 'YY2', in, trophoblast, stem, '(', 'TS)', cells])]). relacion([sujeto(['We']), verbo([report]), complemento([the, presence, of, 'YY2', protein, in, 'mouse-derived', embryonic, stem, '(', 'ES)', and, 'TS', cell, lines])]). relacion([sujeto(['Following', up, on, our, previous]), verbo([report]), complemento([on, 'ERV', binding, by, 'YY2', in, 'TS', 'cells,', we, investigated, the, 'tissue-specificity', of, 'REX1', and, 'YY2', binding, and, confirm, binding, to, 'RE/ERV', targets, in, both, 'ES', cells, and, 'TS', cells])]). relacion([sujeto(['We', used, in, vivo, 'YY2', association, as, a, measure, to, identify, potential]), verbo([target]), complemento([genes])]). relacion([sujeto(['Sequencing', of, chromatin, obtained, in, 'chromatin-immunoprecipitation', '(', 'ChIP)', assays, carried, out, with, αYY2, serum, allowed, us, to, identify, a, limited, number, of, chromatin]), verbo([targets]), complemento([for, 'YY2'])]). relacion([sujeto(['Some', putative]), verbo([binding]), complemento([sites, were, validated, in, regular, 'ChIP', assays, and, gene, expression, of, genes, nearby, was, altered, in, the, absence, of, 'Yy2'])]). relacion([sujeto(['YY2']), verbo([binding]), complemento([to, 'ERVs', is, not, confined, to, 'TS', cells])]). relacion([sujeto(['In', vivo]), verbo([binding]), complemento([sites, share, the, presence, of, a, consensus, binding, motif])]). relacion([sujeto(['Selected', sites, were, uniquely]), verbo([bound]), complemento([by, 'YY2', as, opposed, to, 'YY1,', suggesting, that, 'YY2', exerts, unique, contributions, to, gene, regulation])]). relacion([sujeto(['YY2']), verbo([binding]), complemento([was, not, generally, associated, with, gene, promoters])]). relacion([sujeto(['However,', several, 'YY2']), verbo([binding]), complemento([sites, are, linked, to, long, noncoding, 'RNA', '(', 'lncRNA)', genes, and, we, show, that, the, expression, levels, of, a, few, of, those, are, 'Yy2-dependent'])]). relacion([sujeto(['To', 'date,', many, regulatory, genes]), verbo([involved]), complemento([in, the, 'ABA', response, network, have, been, 'identified;', 'however,', their, roles, have, remained, to, be, fully, elucidated])]). relacion([sujeto(['The', expression, of, 'AtYY1', was]), verbo([induced]), complemento([by, 'ABA', and, stress, conditions, including, high, salt, and, dehydration])]). relacion([sujeto(['AtYY1']), verbo([loss]), complemento([also, enhanced, 'ABA-induced', stomatal, closing, 'and drought', resistance])]). relacion([sujeto(['Moreover,', 'AtYY1', can]), verbo([bind]), complemento([the, 'ABA', 'REPRESSOR1', '(', 'ABR1)', promoter, and, directly, upregulate, 'ABR1', 'expression,', as, well, as, negatively, regulate, 'ABA-', and, 'salt-responsive', gene, expression])]). relacion([sujeto(['Additional', analysis, indicated, that, 'ABA', 'INSENSITIVE4', '(', 'ABI4) might', positively]), verbo([regulate]), complemento(['AtYY1', expression, and, that, 'ABR1', can, antagonize, this, regulation])]). relacion([sujeto(['Our', findings]), verbo([provide]), complemento([direct, evidence, that, 'AtYY1', is, a, novel, negative, regulator, of, the, 'ABA', response, network, and, that, the, 'ABI4-AtYY1-ABR1', regulatory, pathway, may, 'fine-tune', 'ABA-responsive', gene, expression, in, 'Arabidopsis'])]). relacion([sujeto(['Yin', 'Yang', 1, '(', 'YY1)', is, a, ubiquitously]), verbo([expressed]), complemento(['GLI-Kruppel', zinc, 'finger-containing', transcriptional, regulator])]). relacion([sujeto(['YY1', effects, on, the, genes]), verbo([involved]), complemento([in, these, processes, are, mediated, via, 'initiation,', 'activation,', or, repression, of, transcription, depending, upon, the, context, in, which, it, binds])]). relacion([sujeto(['YY1a', is, first]), verbo([expressed]), complemento([0.5, h, 'post-fertilization', '(', 'hpf),', in, the, whole, embryo, 12, 'hpf,', and, in, 'brain,', 'eyes,', and, heart, 72, hpf, by, in, situ, hybridization, assay])]). relacion([sujeto(['The', nucleotide, sequence, of, zebrafish, 'YY1a', transcription, factor, '(', clone, 'zfYY1a;', 'HQ', 166834, ')', was]), verbo([found]), complemento([to, be, similar, to, that, of, zebrafish, 'YY1a', '(', 99, '%', sequence, 'identity;', 'NM', 212617, ')'])]). relacion([sujeto(['With', the, 'loss-of-function', 'assay,', 'YY1a', knockdown, by, a, morpholino, oligonucleotide]), verbo([led]), complemento([to, downregulation, of, the, phosphatidylserine, engulfing, receptor, zfPSR, during, embryonic, segmentation, and, to, the, accumulation, of, a, large, number, of, dead, apoptotic, cells, throughout, the, entire, early, 'embryo,', especially, in, the, posterior, area])]). relacion([sujeto(['Finally,', with, 'gain-of-function', 'assay,', defective, morphants, could, be, rescued, by, injecting, both, 'YY1a', mRNA, and, 'PSR', mRNA, and]), verbo([trigger]), complemento([resumption, of, normal, development])]). relacion([sujeto(['Taken', 'together,', our, results]), verbo([suggest]), complemento([that, 'YY1a', regulates, 'PS', receptor, expression, that, linked, to, function, of, 'PSR-phagocyte', mediated, apoptotic, cell, engulfment, during, 'development,', especially, the, development, of, organs, such, as, the, brain, and, heart])]). relacion([sujeto(['YY1a/PSR-mediated', engulfing, system, may]), verbo([involve]), complemento([in, diseases])]). relacion([sujeto(['Apart', from, a, slight]), verbo([increase]), complemento([in, the, 'protein\'s', 'compactness,', no, changes, in, the, tertiary, structure, were, observed])]). relacion([sujeto(['The', introduced, mutation, significantly, alters, 'DNA-binding', 'properties,', both, the, affinity, and, 'enthalpy-entropy', contribution, of, the, 'process,', which, are, highly, dependent, on, the]), verbo([recognized]), complemento([sequence])]). relacion([sujeto(['Obtained', results, indicate, concerted, rather, than, a]), verbo([modular]), complemento([mode, of, sequence, recognition, by, 'YY1', with, the, significant, impact, of, a, disordered, 'NTF'])]). relacion([sujeto(['Yin', 'Yang', 1, '(', 'YY1)', is, a, zinc, finger, protein, that, functions, as, a, transcriptional, activator, or, repressor, and]), verbo([participates]), complemento([in, multiple, biological, 'processes,', including, development, and, tumorigenesis])]). relacion([sujeto(['When', 'YY1', was, depleted, in, 'CD4(-)CD8(-)', 'double-negative', 'thymocytes,', development, to, the, 'CD4(+)CD8(+)', 'double-positive', stage, was, 'impaired,', due, to]), verbo([increased]), complemento([apoptosis, that, prevented, expansion, of, 'post-β-selection', thymocytes])]). relacion([sujeto(['When', 'YY1', was, depleted, in, 'double-positive', 'thymocytes,', they, underwent]), verbo([increased]), complemento(['cell-autonomous', apoptosis, in, vitro, and, displayed, a, shorter, lifespan, in, 'vivo,', as, judged, by, their, ability, to, undergo, secondary, 'Vα-to-Jα', recombination])]). relacion([sujeto(['Mechanistically,', we]), verbo([found]), complemento([that, the, increased, apoptosis, in, 'YY1-deficient', thymocytes, was, attributed, to, overexpression, of, 'p53,', because, concurrent, loss, of, p53, completely, rescued, the, developmental, defects, of, 'YY1-deficient', thymocytes])]). relacion([sujeto(['These', results, indicated, that, 'YY1', functions, as, a, critical, regulator, of, thymocyte, survival, and, that, it, does, so, by]), verbo([suppressing]), complemento([the, expression, of, p53])]). relacion([sujeto(['Nuclear', factor, '(', 'erythroid-derived', 2, ')', -, like, 2, '(', 'Nrf2)']), verbo([regulates]), complemento([the, induction, of, antioxidant, gene, expression, and, protects, cells, against, oxidative, injury])]). relacion([sujeto(['Irradiation']), verbo([inhibited]), complemento([osteoblast, differentiation, of, 'MC3T3-E1', cells, in, a, 'dose-dependent', manner])]). relacion([sujeto(['This', inhibition, was, evidenced, by, the, 'irradiation-mediated']), verbo([decreases]), complemento([in, 'bone-like', nodule, 'formation,', alkaline, phosphatase, '(', 'ALP)', 'activity,', calcium, 'accumulation,', and, expression, of, osteoblast, 'markers,', such, as, 'ALP,', 'osteocalcin,', 'osteopontin,', bone, 'sialoprotein,', 'osterix,', and, 'Runx2'])]). relacion([sujeto(['These', reductions, were, accompanied, by]), verbo([increased]), complemento([induction, of, 'Nrf2', and, heme, 'oxygenase-1', '(', 'HO-1),', accumulation, of, cellular, 'oxidants,', and, depletion, of, antioxidant, defense, enzymes])]). relacion([sujeto(['siRNA-mediated', silencing, of, 'Nrf2', markedly, reversed, the, negative, effect, of, irradiation, on, osteoblast, differentiation, of, the, 'cells,']), verbo([leading]), complemento([to, a, decrease, in, 'HO-1', and, an, increase, in, 'Runx2', levels])]). relacion([sujeto(['Irradiation-mediated']), verbo([decreases]), complemento([in, the, levels, of, 'Runx2', and, osteocalcin, 'mRNA,', but, not, of, 'Nrf2', 'protein,', were, also, significantly, inhibited, by, 'HO-1', 'inhibitor,', zinc, protoporphyrin, 'IX'])]). relacion([sujeto(['Furthermore,', 'N-acetyl', cysteine, restored, all, of, the, changes]), verbo([induced]), complemento([by, irradiation, to, 'near-normal', levels, in, the, cells])]). relacion([sujeto(['These', results, demonstrate, that, irradiation]), verbo([inhibits]), complemento([osteoblast, differentiation, and, mineralization, of, 'MC3T3-E1', cells, through, the, oxidative, 'stress-mediated', activation, of, 'Nrf2/HO-1', pathway])]). relacion([sujeto(['Interleukin', '(', 'IL)-4']), verbo([acts]), complemento([on, 'T', cells, as, a, growth, and, activation, 'factor,', and, promotes, the, differentiation, of, type, 2, 'T', helper, cells])]). relacion([sujeto(['In', 'T', 'cells,', expression, of, the, gene, encoding, 'IL-4', is]), verbo([regulated]), complemento([by, inducible, or, constitutive, factors])]). relacion([sujeto(['Yin-Yang', '(', 'YY)-1', is, one, of, constitutive, transcription, factors]), verbo([binding]), complemento([to, the, 'IL-4', promoter])]). relacion([sujeto(['YY1', and, 'YY2', were, constitutively]), verbo([expressed]), complemento([in, 'EL4', 'T', 'cells,', and, their, expression, was, not, dependent, on, stimulation])]). relacion([sujeto(['IL-4', promoter, '(', -, 741, /, +, 56, 'fragment)', activity, was]), verbo([enhanced]), complemento([by, 'YY1,', but, inhibited, by, 'YY2'])]). relacion([sujeto(['The']), verbo([enhanced]), complemento(['IL-4', promoter, activity, by, 'YY1', was, reduced, by, simultaneous, expression, of, 'YY2'])]). relacion([sujeto(['In', 'addition,', the, 'DNA']), verbo([binding]), complemento([affinity, of, 'YY1', to, the, 'IL-4', promoter, was, adversely, affected, by, 'YY2'])]). relacion([sujeto(['Our', results]), verbo([suggest]), complemento([that, 'YY1', and, 'YY2', exert, opposing, effects, on, the, 'IL-4', promoter, as, they, compete, for, the, same, 'DNA', binding, sites])]). relacion([sujeto(['Yin', 'Yang', 1, '(', 'YY1)', is, a, multifunctional, 'zinc-finger-containing', transcription, factor, that, plays, crucial, roles, in, numerous, biological, processes, by, selectively]), verbo([activating]), complemento([or, repressing, 'transcription,', depending, upon, promoter, contextual, differences, and, specific, protein, interactions])]). relacion([sujeto(['It', impaired, tracheal, cartilage, 'formation,', altered, cell, 'differentiation,', abrogated, lung, branching, and]), verbo([caused]), complemento([airway, dilation, similar, to, that, seen, in, human, congenital, cystic, lung, diseases])]). relacion([sujeto(['The', cystic, lung, phenotype, in, 'Yy1', mutants, can, be, partly, explained, by, the, reduced, expression, of, 'Shh,', a, transcriptional]), verbo([target]), complemento([of, 'YY1,', in, lung, 'endoderm,', and, the, subsequent, derepression, of, mesenchymal, 'Fgf10', expression])]). relacion([sujeto(['Analysis', of, human, lung, tissues, revealed]), verbo([decreased]), complemento(['YY1', expression, in, children, with, pleuropulmonary, blastoma, '(', 'PPB),', a, rare, pediatric, lung, tumor, arising, during, fetal, development, and, associated, with, 'DICER1', mutations])]). relacion([sujeto(['We', previously, conducted, a, 'genome-wide', association, study, '(', 'GWAS)', and, detected, two, loci]), verbo([associated]), complemento([with, 'AIS'])]). relacion([sujeto(['To', identify, additional, 'loci,', we, extended, our, 'GWAS', by]), verbo([increasing]), complemento([the, number, of, cohorts, '(', 2, ',', 109, affected, subjects, and, 11, ',', 140, control, subjects, in, 'total)', and, conducting, a, 'whole-genome', imputation])]). relacion([sujeto(['The', most, significantly]), verbo([associated]), complemento(['SNPs', were, in, intron, 3, of, 'BNC2,', which, encodes, a, zinc, finger, transcription, 'factor,', 'basonuclin-2'])]). relacion([sujeto(['Expression', quantitative, trait, loci, data]), verbo([suggested]), complemento([that, the, associated, 'SNPs', have, the, potential, to, regulate, the, 'BNC2', transcriptional, activity, and, that, the, susceptibility, alleles, increase, 'BNC2', expression])]). relacion([sujeto(['We', identified, a, functional, 'SNP,', rs10738445, in, 'BNC2,', whose, susceptibility, allele, showed, both, higher]), verbo([binding]), complemento([to, a, transcription, 'factor,', 'YY1', '(', yin, and, yang, 1, ')', ',', and, higher, 'BNC2', enhancer, activity, than, the, 'non-susceptibility', allele])]). relacion([sujeto(['Our', results]), verbo([suggest]), complemento([that, increased, 'BNC2', expression, is, implicated, in, the, etiology, of, 'AIS'])]). relacion([sujeto(['The', mechanism, by, which, 'YY1']), verbo([regulates]), complemento([adipocyte, differentiation, remains, unclear])]). relacion([sujeto(['During', the, early, 'stage,', 'YY1', gene, and, protein, expression, was, transiently, downregulated, upon, the, induction, of, 'differentiation,', 'however,', it, was, consistently]), verbo([induced]), complemento([during, the, later, stage])]). relacion([sujeto(['YY1', overexpression]), verbo([decreased]), complemento([adipocyte, differentiation, and, blocked, cell, differentiation, at, the, preadipocyte, 'stage,', while, 'YY1', knockdown, by, 'RNA', interference, increased, adipocyte, differentiation])]). relacion([sujeto(['YY1', physically]), verbo([interacted]), complemento([with, 'PPARγ', '(', 'Peroxisome', 'proliferator-activated', receptor, 'gamma)', and, 'C/EBPβ', '(', 'CCAAT/enhancer-binding', protein, 'beta)', respectively, in, 3, 'T3-L1', cells])]). relacion([sujeto(['Through', its, interaction, with, 'PPARγ,', 'YY1', directly]), verbo([decreased]), complemento(['PPARγ', transcriptional, activity])]). relacion([sujeto(['YY1', ectopic, expression]), verbo([prevented]), complemento(['C/EBPβ', from, binding, to, the, 'PPARγ', 'promoter,', resulting, in, the, downregulation, of, 'PPARγ', transcriptional, activity])]). relacion([sujeto(['Most', recent, studies, focused, on, the, identification, of, matrix, proteins]), verbo([involved]), complemento([in, shell, 'formation;', 'however,', little, is, known, about, their, transcriptional, regulation, 'mechanism,', especially, the, transcription, factors, involved, in, shell, formation])]). relacion([sujeto(['Pf-YY-1']), verbo([has]), complemento([a, typical, zinc, finger, motif, highly, similar, to, those, in, 'humans,', 'mice,', and, other, higher, 'organisms,', which, indicated, its, 'DNA-binding', capability, and, its, function, as, a, transcription, factor])]). relacion([sujeto(['Pf-YY-1', is, ubiquitously]), verbo([expressed]), complemento([in, many, 'tissues,', but, at, a, higher, level, in, the, 'mantle,', which, suggested, a, role, in, biomineralization])]). relacion([sujeto(['The', expression, pattern, of, 'Pf-YY-1', during, pearl, sac, development, was, quite, similar, 'to,', and, was, synchronized, 'with,', those, of, 'Prisilkin-39,', 'ACCBP,', and, other, genes]), verbo([involved]), complemento([in, 'biomineralization,', which, also, suggested, its, function, in, biomineralization])]). relacion([sujeto(['YY1', is]), verbo([involved]), complemento([in, the, regulation, of, a, broad, spectrum, of, cellular, processes, such, as, 'embryogenesis,', 'proliferation,', 'tumorigenesis,', and, snRNA, transcription])]). relacion([sujeto(['The', more, than, 100]), verbo([reported]), complemento([targets, of, the, 'YY1', protein, suggest, that, it, contains, intrinsically, disordered, regions, that, are, involved, in, such, diverse, interactions])]). relacion([sujeto(['To', facilitate, our, exploration, of, the, 'YY1', 'structure,', the, 'full-length', protein, as, well, as, an, 'N-terminal', fragment, '(', residues, 1, -, 295, ')', and, the, 'C-terminal', 'DNA']), verbo([binding]), complemento([domain, were, used])]). relacion([sujeto(['We']), verbo([found]), complemento([the, 'N-terminus', to, be, a, 'non-compact', fragment, of, 'YY1', with, little, residual, secondary, structure, and, lacking, a, 'well-defined', tertiary, structure])]). relacion([sujeto([microRNAs, '(', 'miRNAs)']), verbo([have]), complemento([been, reported, to, play, important, regulatory, roles, in, cancer, metastasis, and, progression])]). relacion([sujeto(['miR-34a']), verbo([has]), complemento([been, demonstrated, to, be, associated, with, the, development, of, and, metastasis, in, certain, types, of, cancer, via, various, target, 'genes,', but, its, function, and, targets, in, 'ESCC', are, unknown])]). relacion([sujeto(['The', aim, of, this, study, was, to, examine, whether, the, expression, of, 'miR-34a', was, significantly]), verbo([decreased]), complemento([in, 'ESCC', 'tissues,', compared, with, normal, esophageal, tissues, using, 'RT-PCR', and, western, blot, analysis])]). relacion([sujeto(['The', results, showed, that, 'miR-34a', overexpression]), verbo([increased]), complemento([apoptosis, and, decreased, clonogenic, 'formation,', but, inhibited, invasion, and, migration, in, 'ESCC', cells, by, suppressing, 'MMP-2', and, -, 9, expression])]). relacion([sujeto(['Yin', 'Yang-1', '(', 'YY1),', a, widely, distributed, transcription, factor, that, belongs, to, the, 'GLI-Kruppel', class, of, zinc, finger, 'proteins,', was]), verbo([found]), complemento([to, be, a, direct, target, of, 'miR-34a', in, 'ESCC', cell, lines])]). relacion([sujeto(['Rescue', experiments, indicated, that, the, suppressive, effect, of, 'miR-34a', on, invasion, and, migration, was]), verbo([mediated]), complemento([by, activating, 'YY1', expression])]). relacion([sujeto(['Results', of, the, present, study, showed, that, 'miR-34a', is]), verbo([associated]), complemento([with, 'ESCC', migration, and, provides, a, potential, therapeutic, and, diagnostic, target, for, 'ESCC'])]). relacion([sujeto(['Exome', and]), verbo([targeted]), complemento([sequencing, revealed, that, 14, of, 43, insulinomas, harbored, the, identical, somatic, mutation, in, the, 'DNA-binding', zinc, finger, of, the, transcription, factor, 'Yin', 'Yang', 1, '(', 'YY1)'])]). relacion([sujeto(['Chromatin', immunoprecipitation, sequencing, '(', 'ChIP-Seq)', showed, that, this, 'T372R', substitution, changes, the, 'DNA', motif]), verbo([bound]), complemento([by, 'YY1'])]). relacion([sujeto(['Genes', showing, large]), verbo([increases]), complemento([in, expression, in, 'YY1(T372R)', tumors, included, 'ADCY1', '(', an, adenylyl, 'cyclase)', and, 'CACNA2D2', '(', a, 'Ca(2+)', 'channel);', both, are, expressed, at, very, low, levels, in, normal, 'β-cells', and, show, 'mutation-specific', 'YY1', binding, sites])]). relacion([sujeto(['Both', gene, products, are]), verbo([involved]), complemento([in, key, pathways, regulating, insulin, secretion])]). relacion([sujeto(['Expression', of, these, genes, in, rat, 'INS-1', cells, demonstrated, markedly]), verbo([increased]), complemento([insulin, secretion])]). relacion([sujeto(['These', findings, indicate, that, 'YY1(T372R)', mutations, are, 'neomorphic,', resulting, in, constitutive, activation, of, cAMP, and, 'Ca(2+)', signaling, pathways]), verbo([involved]), complemento([in, insulin, secretion])]). relacion([sujeto(['Gene', transcription, is, tightly]), verbo([regulated]), complemento([at, different, levels, to, ensure, that, the, transcriptome, of, the, cell, is, appropriate, for, developmental, stage, and, cell, type])]). relacion([sujeto(['Recent', biochemical, purifications, of, such, complexes]), verbo([have]), complemento([revealed, a, substantial, diversity])]). relacion([sujeto(['On', the, one, 'hand,', complexes, that, were, thought, to, be, unique]), verbo([have]), complemento([been, revealed, to, be, part, of, large, complex, families])]). relacion([sujeto(['On', the, other, 'hand,', protein, subunits, that, were, thought, to, only, exist, in, separate, complexes]), verbo([have]), complemento([been, shown, to, coexist, in, novel, assemblies])]). relacion([sujeto(['In', this, review, we, discuss, our, current, knowledge, of, repressor, complexes, that, contain, 'MBT', domain, proteins, 'and/or', the, 'CoREST', 'co-repressor', and, use, them, as, a, paradigm, to, illustrate, the, unexpected, heterogeneity, and, tool, sharing, of, chromatin]), verbo([regulating]), complemento([protein, complexes])]). relacion([sujeto(['The', 'Transwell', assay, revealed, that, the, overexpression, of, 'YY1']), verbo([promoted]), complemento([the, invasion, ability, of, 'TE-1', cells, and, the, inhibition, of, 'YY1', could, reverse, this, promotion])]). relacion([sujeto(['YY1', expression, was]), verbo([associated]), complemento([with, 'TNM', stage, and, lymph, node, 'metastasis,', suggesting, that, 'YY1', can, influence, human, esophageal, cancer, progression, and, metastasis])]). relacion([sujeto(['The', genomic]), verbo([binding]), complemento([of, 'CTCF', is, highly, conserved, across, 'mammals,', but, the, mechanisms, that, underlie, its, stability, are, poorly, understood])]). relacion([sujeto(['One', transcription, factor, known, to, functionally]), verbo([interact]), complemento([with, 'CTCF', in, the, context, of, 'X-chromosome', inactivation, is, the, ubiquitously, expressed, 'YY1'])]). relacion([sujeto(['Because', combinatorial, transcription, factor]), verbo([binding]), complemento([can, contribute, to, the, evolutionary, stabilization, of, regulatory, 'regions,', we, tested, whether, 'YY1', and, 'CTCF', 'co-binding', could, in, part, account, for, conservation, of, 'CTCF', binding])]). relacion([sujeto(['Combined', analysis, of, 'CTCF', and, 'YY1']), verbo([binding]), complemento([in, lymphoblastoid, cell, lines, from, seven, 'primates,', as, well, as, in, mouse, and, human, 'livers,', reveals, extensive, 'genome-wide', 'co-localization', specifically, at, evolutionarily, stable, 'CTCF-bound', regions])]). relacion([sujeto(['CTCF-YY1', 'co-bound', regions, resemble, regions]), verbo([bound]), complemento([by, 'YY1', 'alone,', as, they, enrich, for, active, histone, 'marks,', 'RNA', polymerase, 'II', and, transcription, factor, binding])]). relacion([sujeto(['Our', results]), verbo([reveal]), complemento([that, these, two, ubiquitously, 'expressed,', 'multi-functional', 'zinc-finger', proteins, collaborate, in, functionally, active, regions, to, stabilize, one, 'another\'s', 'genome-wide', binding, across, primate, evolution])]). relacion([sujeto(['Ying', 'Yang', 1, '(', 'YY1),', a, ubiquitously]), verbo([expressed]), complemento(['GLI-Krüppel', zinc, finger, transcription, 'factor,', plays, a, regulatory, role, in, a, variety, of, fundamental, biological, 'processes,', such, as, embryonic, 'development,', 'growth,', 'apoptosis,', differentiation, and, oncogenic, transformation])]). relacion([sujeto(['We']), verbo([found]), complemento([that, the, expression, of, 'YY1', mRNA, was, significantly, increased, in, the, tumor, 'tissues,', compared, with, the, 'para-tissues', or, normal, esophageal, tissues])]). relacion([sujeto(['The']), verbo([increased]), complemento([expression, of, 'YY1', in, tumor, samples, was, further, confirmed, by, immunohistochemistry])]). relacion([sujeto(['Furthermore,', the, overexpression, of, 'YY1']), verbo([conferred]), complemento([radioresistance, to, the, 'ESCC', 'TE-1', cells, and, resulted, in, markedly, reduced, cell, proliferation])]). relacion([sujeto(['Accordingly,', the, small, interfering, 'RNA-mediated', silencing, of, 'YY1', expression, in, 'TE-1', cells, resulted, in]), verbo([increased]), complemento([proliferation, by, enhancing, the, binding, of, 'P21', to, 'Cyclin', 'D1', and, 'CDK4,', a, protein, complex, known, to, mediate, cell, cycle, progression])]). relacion([sujeto(['Moreover,', besides, 'P21,', heme, 'oxygenase-1', '(', 'HO-1)', was, identified, as, a, 'YY1', downstream, 'effector,', as, 'YY1']), verbo([stimulated]), complemento(['HO-1', expression, in, esophageal, cancer, cells])]). relacion([sujeto(['YY1']), verbo([mediated]), complemento([biological, function, through, transcription, of, 'HO-1'])]). relacion([sujeto(['Forced', expression, of, 'HO-1', could, moderately]), verbo([suppress]), complemento([proliferation, of, 'TE-1', cells])]). relacion([sujeto(['To', investigate, the, role, of, 'IKKβ', in, regulation, of, 'hematopoiesis,', we, employed, 'Mx1-Cre']), verbo([mediated]), complemento(['IKKβ', conditional, knockout, mice])]). relacion([sujeto(['As', previously, 'reported,', deletion, of, 'IKKβ', in, hematopoietic, cells, results, in, 'neutrophilia,', and, we, now, also, noted]), verbo([decreased]), complemento([monocytes, and, modest, anemia])]). relacion([sujeto(['Accordingly,', we]), verbo([found]), complemento([a, significantly, reduced, frequency, of, proerythroblasts, and, basophilic, and, polychromatic, 'erythroblasts,', and, 'IKKβ-deficient', bone, marrow, cells, yielded, a, significantly, decreased, number, of, 'BFU-E', compared, to, wild, type])]). relacion([sujeto(['These', changes, are]), verbo([associated]), complemento([with, elevated, expression, of, 'C/EBPα,', 'Gfi1,', and, 'PU'])]). relacion([sujeto(['In', 'contrast,', no, effect, on, erythropoiesis, or, expression, of, 'lineage-related', transcription, factors, was]), verbo([found]), complemento([in, marrow, lacking, 'NF-κB', p65])]). relacion([sujeto(['Bone', marrow, from, 'IKKβ', knockout, mice]), verbo([has]), complemento([elevated, numbers, of, phenotypic, long, and, short, term, hematopoietic, stem, cells, '(', 'HSC)'])]). relacion([sujeto(['A', similar]), verbo([increase]), complemento([was, observed, when, 'IKKβ', was, deleted, after, marrow, transplantation, into, a, wild, type, 'host,', indicating, cell, autonomous, expansion])]). relacion([sujeto(['Myeloid', progenitors, from, 'IKKβ-', but, not, 'p65-deleted', mice, demonstrate]), verbo([increased]), complemento([serial, replating, in, 'colony-forming', 'assays,', indicating, increased, cell, autonomous, 'self-renewal', capacity])]). relacion([sujeto(['In', 'summary,']), verbo([loss]), complemento([of, 'IKKβ', resulted, in, significant, effects, on, hematopoiesis, not, seen, upon, 'NF-κB', p65, deletion])]). relacion([sujeto(['These', include]), verbo([increased]), complemento([myeloid, and, reduced, erythroid, transcription, 'factors,', skewing, differentiation, towards, myeloid, over, erythroid, 'differentiation,', increased, progenitor, 'self-renewal,', and, increased, number, of, functional, long, term, 'HSCs'])]). relacion([sujeto(['In', the, present, 'research,', we]), verbo([have]), complemento([studied, an, influence, of, enhanced, expression, 'TRIM14', on, alphavirus, 'Sindbis', '(', 'SINV,', 'Togaviridae', 'family)', infection])]). relacion([sujeto(['In', the, 'HEK293', cells, transfected, with, human, trim14, gene, '(', 'HEK-trim14),', 'SINV', yield, after, infection, was]), verbo([decreased]), complemento([1000, -, 10, ',', 0, times, '(', 3, -, 4, lg, of, 'TCD50/ml)', at, 24, h, p])]). relacion([sujeto(['Analysis', of, the, expression, of, 43, genes, directly, or, indirectly]), verbo([involved]), complemento([in, innate, immune, machine, in, 'HEK-trim14', 'non-infected', cells, comparing, with, the, control, '(', 'non-transfected)', 'HEK293', cells, revealed, that, stable, trim14, transfection, in, 'HEK293', cells, caused, increased, transcription, of, 18, genes, '(', 'ifna,', il6, '(', 'ifnβ2),', 'isg15,', 'raf-1,', 'NF-kB', '(', 'nf-kb1,', 'rela,', 'nf-kb2,', 'relb),', 'grb2,', 'grb3-3,', 'traf3ip2,', 'junB,', 'c-myb,', pu])]). relacion([sujeto(['However,', 'SINV', infection, of, 'HEK-trim14', cells]), verbo([caused]), complemento([inhibition, of, the, most, interferon, cascade, genes, as, well, as, subunits, of, transcription, factor, 'NF-κB'])]). relacion([sujeto(['Thus,', stable]), verbo([enhanced]), complemento([expression, of, trim14, gene, in, cells, activates, the, transcription, of, many, immunity, genes, and, suppresses, the, 'SINV', 'reproduction,', but, 'SINV', infection, of, 'HEK-trim14', cells, promotes, inhibition, of, some, genes, involved, in, innate, immune, system])]). relacion([sujeto(['Activin', 'A,', a, member, of, the, transforming, growth, factor, '(', 'TGF)-β', 'superfamily,']), verbo([induces]), complemento([the, erythropoiesis, of, hematopoietic, progenitor, cells])]). relacion([sujeto(['In', this, 'study,', a, luciferase, reporter, assay, showed, that, 'IFN-γ']), verbo([suppressed]), complemento([activin, 'A-induced', 'ζ-globin', promoter, activation, in, 'K562', erythroblast, cells, in, a, 'dose-dependent', manner])]). relacion([sujeto(['IFN-γ', also]), verbo([suppressed]), complemento([the, activation, of, activin, 'A-induced', 'α-globin', promoter])]). relacion([sujeto(['IFN-γ', reduced, the, mRNA, expression, of, 'α-globin,', 'ζ-globin,', 'NF-E2p45,', and, 'GATA-1']), verbo([induced]), complemento([by, activin, 'A'])]). relacion([sujeto(['The', results, also, showed, that, 'IFN-γ']), verbo([induced]), complemento(['c-Jun', expression, when, 'NF-κBp65', and, 'c-Jun', bound, to, two, 'AP-1-binding', sites, on, the, 'c-Jun', promoter])]). relacion([sujeto(['The', luciferase, activity, of, 'α-globin', and, 'ζ-globin', promoters, were]), verbo([enhanced]), complemento([by, 'wild-type', 'c-Jun', and, eliminated, by, 'dominant-negative', '(', 'DN)', 'c-Jun'])]). relacion([sujeto(['The', suppressive, effects, of, 'IFN-γ', on, the, mRNA, expression, of, 'α-globin', and, 'ζ-globin', were, absent, in, cells]), verbo([expressing]), complemento(['DN', 'c-Jun'])]). relacion([sujeto(['The', ability, of, 'NF-E2', to]), verbo([enhance]), complemento([activin, 'A-induced', 'ζ-globin', promoter, activation, decreased, when, 'c-Jun', was, 'present,', and, 'IFN-γ', treatment, further, enhanced, the, decreasing, effect, of, 'c-Jun'])]). relacion([sujeto(['Chromatin', immunoprecipitation, revealed, that, 'NF-E2p45']), verbo([bound]), complemento([to, the, upstream, regulatory, element, '(', 'HS-40)', of, the, 'α-globin', gene, cluster, in, response, to, activin, 'A,', whereas, 'c-Jun', eliminated, this, binding])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, 'IFN-γ', modulates, 'NF-κB/c-Jun', to, antagonize, activin, 'A-mediated', 'NF-E2', transcriptional, activity, on, globin, gene, expression])]). relacion([sujeto(['The', aim, of, this, research, is, to]), verbo([provide]), complemento([an, accurate, phenotypic, characterisation, of, nonsyndromic, 'PRS,', specifically, the, 'PRS-Plus', subgroup])]). relacion([sujeto(['We', sought, to, examine, the, frequency, of, sequence, variants, in, previously, defined]), verbo([conserved]), complemento([noncoding, elements, '(', 'CNEs)', in, the, putative, enhancer, region, upstream, of, 'SOX9,', the, regulation, of, which, has, been, associated, with, 'PRS', phenotypes])]). relacion([sujeto(['We']), verbo([found]), complemento([83, children, with, isolated, 'PRS', and, 58, with, 'PRS-Plus'])]). relacion([sujeto(['The', most, common, 'PRS-Plus', malformations]), verbo([involved]), complemento([the, musculoskeletal, and, ocular, systems])]). relacion([sujeto(['We']), verbo([found]), complemento([a, single, nucleotide, substitution, in, a, putative, 'GATA1-binding', site, in, one, 'patient,', but, it, was, inherited, from, his, phenotypically, unaffected, mother])]). relacion([sujeto(['Terminal', erythroid, differentiation, is, tightly, coordinated, with, cell, cycle, 'exit,', which, is]), verbo([regulated]), complemento([by, 'cyclins,', 'cyclin-dependent', kinases, and, 'cyclin-dependent', kinase, inhibitors, '(', 'CDKI),', yet, their, roles, in, erythropoiesis, remain, to, be, fully, defined])]). relacion([sujeto(['We', show, here, that, 'p19(INK4d),', a, member, of, 'CDKI', 'family,', is, abundantly]), verbo([expressed]), complemento([in, erythroblasts, and, that, 'p19(INK4d)', knockdown, delayed, erythroid, 'differentiation,', inhibited, cell, 'growth,', led, to, increased, apoptosis, and, generation, of, abnormally, nucleated, late, stage, erythroblasts])]). relacion([sujeto(['Rather', it]), verbo([led]), complemento([to, decreased, expression, of, 'GATA1', protein])]). relacion([sujeto(['Importantly,', the, differentiation, and]), verbo([nuclear]), complemento([defects, were, rescued, by, ectopic, expression, of, 'GATA1'])]). relacion([sujeto(['As', 'GATA1', protein, is, protected, by]), verbo([nuclear]), complemento(['HSP70,', we, examined, the, effects, of, 'p19(INK4d)', knockdown, on, 'HSP70', and, found, that, 'p19(INK4d)', knockdown, led, to, decreased, expression, of, 'HSP70', and, its, nuclear, localization])]). relacion([sujeto(['Further', biochemical, analysis, revealed, that, 'p19(INK4d)', directly]), verbo([binds]), complemento([to, 'Raf', kinase, inhibitor, 'PEBP1', and, that, 'p19(INK4d)', knockdown, increased, the, expression, of, 'PEBP1', that, in, turn, led, to, reduced, 'ERK', activation])]). relacion([sujeto(['Thus', we]), verbo([have]), complemento([identified, an, unexpected, role, for, 'p19(INK4d)', via, a, novel, 'PEBP1-pERK-HSP70-GATA1', pathway])]). relacion([sujeto(['These', findings, are, likely, to]), verbo([have]), complemento([implications, for, improved, understanding, of, disordered, erythropoiesis])]). relacion([sujeto(['In', this, 'study,', because, excessive, polycythemia, is, a, predominant, trait, in, some, 'high-altitude', dwellers, '(', chronic, mountain, sickness, '[', 'CMS]', or, 'Monge\'s', 'disease)', but, not, others, living, at, the, same, altitude, in, the, 'Andes,', we, took, advantage, of, this, human, experiment, of, nature, and, used, a, combination, of]), verbo([induced]), complemento([pluripotent, stem, cell, 'technology,', 'genomics,', and, molecular, biology, in, this, unique, population, to, understand, the, molecular, basis, for, 'hypoxia-induced', excessive, polycythemia])]). relacion([sujeto(['As', compared, with, 'sea-level', controls, and, 'non-CMS', subjects, who]), verbo([responded]), complemento([to, hypoxia, by, increasing, their, 'RBCs', modestly, or, not, at, 'all,', 'respectively,', 'CMS', cells, increased, theirs, remarkably, '(', up, to, 60, -, 'fold)'])]). relacion([sujeto(['Although', there, was, a, switch, from, fetal, to, adult, 'HgbA0', in, all, populations, and, a, concomitant, shift, in, oxygen, 'binding,', we]), verbo([found]), complemento([that, 'CMS', cells, matured, faster, and, had, a, higher, efficiency, and, proliferative, potential, than, 'non-CMS', cells])]). relacion([sujeto(['We', also, demonstrated, that, 'GATA1', is, an, essential, downstream]), verbo([target]), complemento([of, 'SENP1', and, that, the, differential, expression, and, response, of, 'GATA1', and, 'Bcl-xL', are, a, key, mechanism, underlying, 'CMS', pathology])]). relacion([sujeto(['GATA1', transcription, factor, is]), verbo([required]), complemento([for, murine, 'DC', 'development,', and, data, suggest, that, it, might, be, involved, in, the, 'fine-tuning', of, the, life, span, and, function, of, activated, 'DCs'])]). relacion([sujeto(['We', generated, 'DC-specific', 'Gata1', knockout, mice, '(', 'Gata1-KO(DC)),', which, presented, a, 20, '%', reduction, of, splenic, 'DCs,', partially, explained, by]), verbo([enhanced]), complemento([apoptosis])]). relacion([sujeto(['RNA', sequencing, analysis, revealed, a, number, of, deregulated, genes]), verbo([involved]), complemento([in, cell, 'survival,', 'migration,', and, function])]). relacion([sujeto(['Interestingly,', we, show, that, 'Gata1-KO(DC)', 'DCs']), verbo([have]), complemento([reduced, polysialic, acid, levels, on, their, 'surface,', which, is, a, known, determinant, for, the, proper, migration, of, 'DCs', toward, 'CCL21'])]). relacion([sujeto(['However,', molecular, mechanisms]), verbo([regulating]), complemento([sequential, generation, of, primitive, erythrocytes, and, multipotent, hematopoietic, progenitors, in, the, yolk, sac, are, largely, unknown])]). relacion([sujeto(['In', this, 'study,', the, transcription, factors]), verbo([involved]), complemento([in, the, development, of, hematopoietic, cells, were, examined, in, purified, progenitor, cell, populations, from, pluripotent, stem, cell, cultures, and, from, the, yolk, sac, of, developing, embryos])]). relacion([sujeto(['We']), verbo([found]), complemento([that, the, earliest, committed, hematopoietic, progenitors, highly, expressed, 'Gata1,', 'Scl/tal1,', and, 'Klf1', genes])]). relacion([sujeto([1, is]), verbo([involved]), complemento([in, the, multipotent, cell, differentiation, through, the, suppression, of, erythroid, transcription, program])]). relacion([sujeto(['Transient', abnormal, myelopoesis, is, mostly, 'self-resolving', and]), verbo([has]), complemento([a, good, 'prognosis,', but, some, patients, subsequently, die, of, liver, fibrosis])]). relacion([sujeto(['We']), verbo([report]), complemento([the, case, of, an, infant, with, 'Down', syndrome, who, developed, 'life-threatening', liver, fibrosis, at, the, same, time, as, the, blasts, were, about, to, disappear])]). relacion([sujeto(['This', patient, also, had, a, marked]), verbo([increase]), complemento([in, 'eosinophils,', which, were, possibly, harboring, a, 'GATA1', mutation, and, were, expressing, a, high, level, of, 'platelet-derived', growth, 'factor-B', 'mRNA;', these, may, have, been, involved, in, the, development, of, liver, fibrosis])]). relacion([sujeto(['Gene', expression, in, mammals, is]), verbo([regulated]), complemento([by, noncoding, elements, that, can, affect, physiology, and, 'disease,', yet, the, functions, and, target, genes, of, most, noncoding, elements, remain, unknown])]). relacion([sujeto(['We', present, a, 'high-throughput', approach, that, uses, clustered, regularly, interspaced, short, palindromic, repeats, '(', 'CRISPR)', interference, '(', 'CRISPRi)', to, discover, regulatory, elements, and, identify, their]), verbo([target]), complemento([genes])]). relacion([sujeto(['Quantitative', features, of, chromatin, state, and, chromosome, conformation, distinguish, the, seven, enhancers, that]), verbo([regulate]), complemento(['MYC', from, other, elements, that, do, 'not,', suggesting, a, strategy, for, predicting, 'enhancer-promoter', connectivity])]). relacion([sujeto(['Increasing', evidence]), verbo([has]), complemento([also, suggested, a, role, for, 'DNMT1', in, repressing, gene, expression, through, interactions, with, specific, transcription, factors])]). relacion([sujeto(['Previously,', we, identified, 'DNMT1', as, an]), verbo([interacting]), complemento([partner, of, the, 'TR2/TR4', nuclear, receptor, heterodimer, in, erythroid, 'cells,', implicated, in, the, developmental, silencing, of, fetal, 'β-type', globin, genes, in, the, adult, stage, of, human, erythropoiesis])]). relacion([sujeto(['We']), verbo([provide]), complemento([evidence, for, 'DNMT1', forming, distinct, protein, subcomplexes, with, specific, transcription, factors, and, propose, the, existence, of, a, &, 'quot;core"', 'DNMT1', complex, with, the, transcription, factors, 'ZBP-89', and, 'ZNF143,', which, is, also, present, in, 'non-hematopoietic', cells])]). relacion([sujeto([')', 'PCNA', 'Binding', 'Domain', '(', 'PBD)', located, near, the, 'N-terminus', of, 'DNMT1', as, being, necessary, for]), verbo([mediating]), complemento([interactions, with, the, transcription, factors, described, herein])]). relacion([sujeto(['Lastly,', we]), verbo([provide]), complemento([evidence, for, 'DNMT1', serving, as, a, 'co-repressor', of, 'ZBP-89', and, 'GATA1', acting, through, upstream, regulatory, elements, of, the, 'PU'])]). relacion([sujeto(['(', 32, ')', 'Recently,', transientness]), verbo([has]), complemento([also, been, reported, in, acute, myeloid, leukemia, patients, with, germline, trisomy, 21, 'mosaicism,', and, even, in, cases, with, somatic, trisomy, 21, ',', with, or, without, 'GATA1', mutations])]). relacion([sujeto(['Lymphatic', system, plays, an, important, role, in]), verbo([maintaining]), complemento([the, fluid, homeostasis, and, normal, immune, 'responses,', anatomic, or, functional, obstruction, of, which, leads, to, 'lymphedema,', and, treatments, for, therapeutic, lymphangiogenesis, are, efficiency, for, secondary, lymphedema])]). relacion([sujeto(['Chen,', which]), verbo([has]), complemento([been, used, as, traditional, 'Chinese', medicine, in, 'China', for, treatment, of, 'cardio-', and, 'cerebro-vascular', diseases])]). relacion([sujeto(['The', role, of, 'phosphatidylinositol-3', '(', 'PI-3)-kinase', '(', 'PI3K),', extracellular, 'signal-regulated', kinase, '(', 'ERK)1/2', 'pathways,', 'c-Jun', 'N-terminal', kinase, '(', 'JNK)', and, 'P38', mitogen]), verbo([activated]), complemento([protein, kinases, '(', 'MAPK)', signaling, in, 'PNS-induced', 'VEGF-C', expression, of, 'LECs', by, using, pharmacological, agents, to, block, each, signal])]). relacion([sujeto(['PNS']), verbo([promotes]), complemento([lymphangiogenesis, of, thoracic, duct, in, zebrafish, with, or, without, 'VEGFR3', 'Kinase', inhibitor, 'pre-impairment'])]). relacion([sujeto(['PNS']), verbo([promotes]), complemento(['proliferation,', migration, and, tube, formation, of, 'LECs'])]). relacion([sujeto(['The', tube, formation]), verbo([induced]), complemento([by, 'PNS', could, be, blocked, by, 'VEGFR3', 'Kinase', inhibitor])]). relacion([sujeto(['PNS']), verbo([induce]), complemento(['VEGF-C', expression, of, 'LEC,', which, could, be, blocked, by, 'ERK1/2,', 'PI3K', and, 'P38MAPK', signaling, inhibitors])]). relacion([sujeto(['PNS']), verbo([activates]), complemento([lymphangiogenesis, both, in, vivo, and, in, vitro, by, 'up-regulating', 'VEGF-C', expression, and, activation, of, 'ERK1/2,', 'PI3K', and, 'P38MAPK', signaling])]). relacion([sujeto(['These', findings]), verbo([provide]), complemento([a, novel, insight, into, the, role, of, 'PNS', in, lymphangiogenesis, and, suggest, that, it, might, be, an, attractive, and, suitable, therapeutic, agent, for, treating, secondary, lymphedema, or, other, lymphatic, system, impairment, related, disease])]). relacion([sujeto(['MiR-592']), verbo([has]), complemento([been, identified, as, a, 'neural-enriched', 'microRNA,', plays, an, important, role, in, mNPCs, 'differentiation,', could, induce, astrogliogenesis, differentiation, arrest, 'or/and', enhance, neurogenesis, in, vitro, 'Previous', studies, showed, that, long, noncoding, 'RNAs', '(', 'lncRNAs)', were, involved, in, the, neuronal, development, and, activity])]). relacion([sujeto(['By', the, microarray, analysis, and, luciferase, reporter, 'assays,', we, demonstrated, that, lncRNA, -, 'AK048794,']), verbo([regulated]), complemento([by, transcription, factor, 'GATA1,', functioned, as, a, competing, endogenous, 'RNA', '(', 'ceRNA)', for, 'miR-592', and, led, to, the, 'de-repression', of, its, endogenous, target, 'FAM91A1,', which, is, involved, in, mESC, pluripotency, maintenance])]). relacion([sujeto(['Taken', 'together,', these, observations, imply, that, 'AK048794']), verbo([modulated]), complemento([the, expression, of, multiple, genes, involved, in, mESC, pluripotency, maintenance, by, acting, as, a, ceRNA, for, 'miR-592,', which, may, build, up, the, link, between, the, regulatory, miRNA, network, and, mESC, pluripotency])]). relacion([sujeto(['Children', with, constitutional, trisomy, 21, '(', 'Down', syndrome, '(', 'DS))']), verbo([have]), complemento([a, unique, predisposition, to, develop, myeloid, leukaemia, of, 'Down', syndrome, '(', 'ML-DS)'])]). relacion([sujeto(['TAM', and, 'ML-DS', are]), verbo([caused]), complemento([by, 'co-operation', between, trisomy, 21, ',', which, itself, perturbs, fetal, haematopoiesis, and, acquired, mutations, in, the, key, haematopoietic, transcription, factor, gene, 'GATA1'])]). relacion([sujeto(['These', mutations, are]), verbo([found]), complemento([in, almost, one, third, of, 'DS', neonates, and, are, frequently, clinically, and, haematologcially, '\'', 'silent\''])]). relacion([sujeto(['Protective', vaccination]), verbo([induces]), complemento(['self-healing', of, otherwise, fatal, 'blood-stage', malaria, of, 'Plasmodium', chabaudi, in, female, 'Balb/c', mice])]). relacion([sujeto(['To', trace, processes, critically]), verbo([involved]), complemento([in, 'self-healing,', the, 'liver,', an, effector, against, 'blood-stage', 'malaria,', is, analyzed, for, possible, changes, of, its, transcriptome, in, 'vaccination-protected', in, comparison, to, 'non-protected', mice, toward, the, end, of, the, crisis, phase])]). relacion([sujeto(['Gene', expression, microarray, analyses]), verbo([reveal]), complemento([that, vaccination, does, not, affect, constitutive, expression, of, mRNA, and, lincRNA])]). relacion([sujeto(['However,', malaria]), verbo([induces]), complemento([significant, '(', p, &, 'lt;', 0.01, ')', differences, in, hepatic, gene, and, lincRNA, expression, in, 'vaccination-protected', vs])]). relacion([sujeto(['In', 'vaccination-protected', 'mice,', infections]), verbo([induce]), complemento(['up-regulations', of, 276, genes, and, 40, lincRNAs, and, 'down-regulations', of, 200, genes, and, 43, 'lincRNAs,', 'respectively,', by, &, 'gt;3-fold', as, compared, to, the, corresponding, constitutive, expressions])]). relacion([sujeto(['Massive', 'up-regulations,', partly, by, &, 'gt;100-fold,', are]), verbo([found]), complemento([for, genes, as, 'RhD,', 'Add2,', 'Ank1,', 'Ermap,', and, 'Slc4a,', which, encode, proteins, of, erythrocytic, surface, 'membranes,', and, as, 'Gata1', and, 'Gfi1b,', which, encode, transcription, factors, involved, in, erythrocytic, development])]). relacion([sujeto(['Also,', 'Cldn13', previously, predicted, to, be]), verbo([expressed]), complemento([on, erythroblast, surfaces, is, 'up-regulated', by, &, 'gt;200-fold,', though, claudins, are, known, as, main, constituents, of, tight, junctions, acting, as, paracellular, barriers, between, epithelial, cells])]). relacion([sujeto(['Other', genes, are, 'up-regulated', by, &, 'lt;100-', and, &, 'gt;10-fold,', which, can, be, subgrouped, in, genes, encoding, proteins, known, to, be]), verbo([involved]), complemento([in, 'mitosis,', in, cell, cycle, 'regulation,', and, in, 'DNA', repair])]). relacion([sujeto(['Our', data]), verbo([suggest]), complemento([that, protective, vaccination, enables, the, liver, to, respond, to, 'P'])]). relacion([sujeto(['Anaemia', or]), verbo([decreased]), complemento([blood, haemoglobin, is, the, most, common, blood, disorder, often, characterized, by, reduced, red, blood, cell, '(', 'RBC)', numbers])]). relacion([sujeto(['A', number, of, additional, players, that, are, critical, for, 'RBC', production]), verbo([have]), complemento([been, identified, in, recent, years])]). relacion([sujeto(['Major', technological, 'advances,', such, as, the, development, of, 'RNA', 'interference,', genetically, modified, 'animals,', including, 'zebrafish,', and, imaging, flow, cytometry]), verbo([have]), complemento([led, to, these, 'discoveries;', the, emergence, of, -, omics, approaches, in, combination, with, the, optimization, of, 'ex vivo', erythroid, cultures, have, also, produced, a, more, comprehensive, understanding, of, erythropoiesis])]). relacion([sujeto(['Here', we, summarize, studies, describing, novel, regulators, of, erythropoiesis, that]), verbo([modulate]), complemento([erythroid, cell, production, in, the, context, of, human, erythroid, disorders, involving, 'hypoxia,', iron, 'regulation,', 'immune-related', 'molecules,', and, the, transcription, factor, 'FOXO3'])]). relacion([sujeto(['Lineage-affiliated', transcription, factors, with, the, capacity, for, lineage, 'reprogramming,', positive, 'auto-regulation', and, mutual, inhibition]), verbo([have]), complemento([been, described, as, being, expressed, in, uncommitted, cell, populations])]). relacion([sujeto(['This']), verbo([led]), complemento([to, the, assumption, that, lineage, choice, is, 'cell-intrinsically', initiated, and, determined, by, stochastic, switches, of, randomly, fluctuating, 'cross-antagonistic', transcription, factors])]). relacion([sujeto(['Rather,', our, findings]), verbo([suggest]), complemento([that, these, transcription, factors, are, only, executing, and, reinforcing, lineage, choice, once, made])]). relacion([sujeto(['Children', with, 'Down', syndrome, '(', 'DS)', are, at]), verbo([increased]), complemento([risk, of, developing, distinctive, clonal, myeloid, 'disorders,', including, transient, abnormal, myelopoiesis, '(', 'TAM)', and, myeloid, leukaemia, of, 'DS', '(', 'ML-DS)'])]). relacion([sujeto(['The', small, interfering, 'RNA', '(', 'siRNA)', and, nonspecific, control, siRNA, were, synthesized, to, silence, the]), verbo([target]), complemento([genes])]). relacion([sujeto(['The', results, indicated, that, knockdown, of, 'LSD1', in, 'K562', cell]), verbo([causes]), complemento([increased, 'H3K4', 'di-methylation', at, 'GATA1', locus, and, activates, 'GATA1', 'expression,', demonstrating, that, 'LSD1', represses, 'GATA1', expression, through, 'LSD1-mediated', histone, demethylation])]). relacion([sujeto(['Upon']), verbo([induced]), complemento([erythroid, differentiation, of, 'K562', 'cells,', the, interaction, between, 'GATA2', and, 'LSD1', is, 'decreased,', consistent, with, a, 'de-repression', of, 'GATA1', expression])]). relacion([sujeto(['Meanwhile,', the, interaction, between, 'TAL1', and, 'LSD1', is, 'increased,', which, forms, a, complex, that, efficiently]), verbo([suppresses]), complemento(['GATA2', expression])]). relacion([sujeto(['In', 'conclusion,', these, observations]), verbo([reveal]), complemento([an, elegant, mechanism, to, modulate, 'GATA1', and, 'GATA2', expression, during, erythroid, differentiation])]). relacion([sujeto(['Myeloid', 'CD71+', cells, were, separated, by, the, density, gradient, centrifugation, combined, with, magnetic]), verbo([activated]), complemento([cell, sorting])]). relacion([sujeto(['The', patient, group, with, detected, mutations, had, a, younger, age, of, disease, 'onset,', a, higher, malformation, 'rate,', and, tended, to]), verbo([have]), complemento([a, lower, remission, rate, and, a, higher, 'transfusion-dependence', rate])]). relacion([sujeto(['We', employed, a, screen, for, transcription, factors, allowing, direct, lineage, reprograming, from, fibroblasts, to]), verbo([induced]), complemento([erythroid, 'progenitors/precursors', '(', 'iEPs)'])]). relacion([sujeto(['Our', results, demonstrate, that, direct, lineage, conversion, is, a, suitable, platform, for, defining, and, studying, the, core, factors]), verbo([inducing]), complemento([the, different, waves, of, erythroid, development])]). relacion([sujeto(['The', transcription, factors, 'GATA1', and, 'GATA2', are, fundamental, regulators, of, hematopoiesis, and]), verbo([have]), complemento([overlapping, expression, profiles])]). relacion([sujeto(['GATA2', is]), verbo([expressed]), complemento([in, hematopoietic, stem, cells, and, early, 'erythroid-megakaryocytic', progenitors, and, activates, a, certain, set, of, 'early-phase', 'genes,', including, the, 'GATA2', gene, itself])]). relacion([sujeto(['In', 'contrast,', 'GATA1', is]), verbo([expressed]), complemento([in, relatively, mature, erythroid, progenitors, and, facilitates, the, expression, of, genes, associated, with, 'differentiation,', including, the, 'GATA1', gene, 'itself;', 'however,', 'GATA1', represses, the, expression, of, 'GATA2'])]). relacion([sujeto(['Loss-of-function', analyses, using, mice, 'in vivo']), verbo([have]), complemento([indicated, that, 'GATA2', and, 'GATA1', are, functionally, nonredundant, and, that, neither, can, compensate, for, the, absence, of, the, other])]). relacion([sujeto(['Recent', hematologic, analyses]), verbo([have]), complemento([suggested, that, disturbances, in, the, balance, of, the, 'GATA', factors, are, associated, with, specific, types, of, hematopoietic, disorders])]). relacion([sujeto(['A', recent]), verbo([report]), complemento([by, 'Banno', 'et al'])]). relacion([sujeto(['(', 2016, ')', sheds, new, light, on, the, mechanism, of, the, synergy, between, these, genetic, alterations, by, modeling, hematopoietic, abnormalities, with, 'patient-derived']), verbo([induced]), complemento([pluripotent, stem, cells])]). relacion([sujeto(['GATA1', is, a, transcription, factor]), verbo([expressed]), complemento([in, several, hematopoietic, lineages, and, essential, for, proper, erythropoiesis, and, megakaryopoiesis])]). relacion([sujeto(['Megakaryocyte-specific', 'genes,', such, as, 'GP1BA,', are, known, to, be, directly]), verbo([regulated]), complemento([by, 'GATA1'])]). relacion([sujeto(['Mutations', in, 'GATA1', can]), verbo([lead]), complemento([to, dyserythropoietic, anemia, and, pseudo, 'gray-platelet', syndrome])]). relacion([sujeto(['Selective']), verbo([loss]), complemento([of, 'Gata1', expression, in, adult, mice, results, in, macrothrombocytopenia, with, platelet, 'dysfunction,', characterized, by, an, excess, of, immature, megakaryocytes])]). relacion([sujeto(['To', specifically, analyze, the, impact, of, 'Gata1']), verbo([loss]), complemento([in, mature, committed, 'megakaryocytes,', we, generated, 'Gata1-Lox|Pf4-Cre', mice, '(', 'Gata1cKOMK)'])]). relacion([sujeto(['Supporting', this, notion, we, demonstrate, that, 'Gata1']), verbo([regulates]), complemento([directly, the, transcription, of, 'Syk,', a, tyrosine, kinase, that, functions, downstream, of, 'Clec2', and, 'GPVI', receptors, in, megakaryocytes, and, platelets])]). relacion([sujeto(['Interestingly,', these, mice, present, a, misbalance, of, the, multipotent, progenitor, compartment, and, the, erythroid, 'lineage,', which]), verbo([translates]), complemento([into, compensatory, stress, erythropoiesis, and, splenomegaly])]). relacion([sujeto(['Despite', the, severe, 'thrombocytopenia,', 'Gata1cKOMK', mice, display, a, mild, reduction, of, 'TPO', plasma, 'levels,', and, 'Gata1cKOMK', megakaryocytes, show, a, mild]), verbo([increase]), complemento([in, 'Pf4', mRNA, 'levels;', such, a, misbalance, might, be, behind, the, general, hematopoietic, defects, 'observed,', affecting, locally, normal, 'TPO', and, 'Pf4', levels, at, hematopoietic, stem, cell, niches])]). relacion([sujeto(['Cellular', repressor, of, 'E1A-stimulated', genes, '(', 'CREG)', is, a, novel, gene]), verbo([reported]), complemento([to, be, involved, in, maintaining, the, homeostasis, of, 'ECs'])]). relacion([sujeto(['Compared', with, normal, arteries, from, 'non-diabetic', 'patients,', reduced, 'CREG', expression, and]), verbo([increased]), complemento([apoptosis, were, found, in, the, endothelium, of, atherosclerotic, lesions, from, patients, with, 'T2DM'])]). relacion([sujeto(['In', vitro, treatment, of, 'HUVECs', with, a, high, 'glucose/high', palmitate, medium, also, resulted, in]), verbo([decreased]), complemento(['CREG', expression, and, increased, apoptosis])]). relacion([sujeto(['Moreover,', high, 'glucose/high', palmitate, 'induced-HUVEC', apoptosis, was]), verbo([increased]), complemento([by, the, 'knock-down', of, 'CREG', and, rescued, by, the, 'over-expression', of, 'CREG'])]). relacion([sujeto(['We', also, demonstrated, that, 'GATA1', was, able, to]), verbo([bind]), complemento([to, the, promoter, of, the, human, 'CREG', gene])]). relacion([sujeto(['A', deletion, mutation, at, -, 297, /, -, 292, in, the, 'CREG', promoter, disrupted, 'GATA1']), verbo([binding]), complemento([and, reduced, the, activation, of, 'CREG', transcription, by, approximately, 83.3, '%'])]). relacion([sujeto(['The', 'over-expression', of, 'CREG']), verbo([inhibits]), complemento([high, 'glucose/high', 'palmitate-induced', apoptosis, in, 'HUVECs'])]). relacion([sujeto(['Thus,', 'CREG', might, be, a, potential, therapeutic]), verbo([target]), complemento([for, intervention, of, vascular, complications, related, to, diabetes])]). relacion([sujeto(['Scl', specifies, lateral, plate, mesoderm, to, a, hematopoietic, fate, and, establishes, boundaries, by]), verbo([inhibiting]), complemento([the, cardiac, lineage])]). relacion([sujeto(['Subsequently,', definitive, hematopoietic, stem, cells, '(', 'HSCs)', emerge, from, the, embryo, proper, via, an, 'endothelial-to-hematopoietic', transition, controlled, by, 'Runx1,']), verbo([acting]), complemento([with, 'Scl', and, 'Gata2'])]). relacion([sujeto(['SCL']), verbo([activates]), complemento([transcription, by, recruiting, a, core, complex, on, 'DNA', that, necessarily, includes, 'E2A/HEB,', 'GATA1-3,', 'LIM-only', proteins, 'LMO1/2,', 'LDB1,', and, an, extended, complex, comprising, 'ETO2,', 'RUNX1,', 'ERG,', or, 'FLI1'])]). relacion([sujeto(['These', interactions]), verbo([confer]), complemento([multifunctionality, to, a, complex, that, can, control, cell, proliferation, in, erythroid, progenitors, or, commitment, to, terminal, differentiation, through, variations, in, single, component])]). relacion([sujeto(['Ectopic', 'SCL', and, 'LMO1/2', expression, in, immature, thymocytes]), verbo([activates]), complemento([of, a, stem, cell, gene, network, and, reprogram, cells, with, a, finite, lifespan, into, 'self-renewing', preleukemic, stem, cells, '(', 'pre-LSCs),', an, initiating, event, in, 'T-cell', acute, lymphoblastic, leukemias])]). relacion([sujeto(['Interestingly,', fate, conversion, of, fibroblasts, to, hematoendothelial, cells]), verbo([requires]), complemento([not, only, 'Scl', and, 'Lmo2', but, also, 'Gata2,', 'Runx1,', and, 'Erg,', indicating, a, necessary, collaboration, between, these, transcription, factors, for, hematopoietic, reprogramming])]). relacion([sujeto(['Nonetheless,', full, reprogramming, into, 'self-renewing', multipotent, 'HSCs', may]), verbo([require]), complemento([additional, factors, and, most, 'likely,', a, permissive, microenvironment])]). relacion([sujeto(['Chromosomal', aneuploidy, and, specific, gene, mutations, are]), verbo([recognized]), complemento([early, hallmarks, of, many, oncogenic, processes])]). relacion([sujeto(['However,', the, net, effect, of, these, abnormalities]), verbo([has]), complemento([generally, not, been, explored])]). relacion([sujeto(['We', focused, on, transient, myeloproliferative, disorder, '(', 'TMD)', in, 'Down', 'syndrome,', which, is, characteristically]), verbo([associated]), complemento([with, somatic, mutations, in, 'GATA1'])]). relacion([sujeto(['To', better, understand, functional, interplay, between, trisomy, 21, and, 'GATA1', mutations, in, 'hematopoiesis,', we, constructed, cellular, disease, models, using, human]), verbo([induced]), complemento([pluripotent, stem, cells, '(', 'iPSCs)', and, 'genome-editing', technologies])]). relacion([sujeto(['Comparative', analysis, of, these, engineered, iPSCs, demonstrated, that, trisomy, 21, perturbed, hematopoietic, development, through, the]), verbo([enhanced]), complemento([production, of, early, hematopoietic, progenitors, and, the, upregulation, of, mutated, 'GATA1,', resulting, in, the, accelerated, production, of, aberrantly, differentiated, cells])]). relacion([sujeto(['These', effects, were]), verbo([mediated]), complemento([by, dosage, alterations, of, 'RUNX1,', 'ETS2,', and, 'ERG,', which, are, located, in, a, critical, 4, -, 'Mb', region, of, chromosome, 21])]). relacion([sujeto(['Our', study]), verbo([provides]), complemento([insight, into, the, genetic, synergy, that, contributes, to, 'multi-step', leukemogenesis])]). relacion([sujeto(['The', 'Inhibitor', of, 'DNA', 'Binding', '(', 'Id)', proteins, play, a, crucial, role, in]), verbo([regulating]), complemento([hematopoiesis, and, are, known, to, interact, with, 'E', proteins, and, the, bHLH, family, of, transcription, factors])]). relacion([sujeto(['Current', efforts, seek, to, elucidate, the, individual, roles, of, 'Id', members, in]), verbo([regulating]), complemento([hematopoietic, development, and, specification])]). relacion([sujeto(['We']), verbo([report]), complemento([that, global, 'Id3', ablation, with, 'Tie2Cre-mediated', conditional, ablation, of, 'Id1', in, both, hematopoietic, and, endothelial, cells, '(', 'Id', 'cDKO)', extends, viability, to, 1, year, but, leads, to, 'multi-lineage', hematopoietic, defects, including, the, emergence, of, anemia, associated, with, defective, erythroid, 'development,', a, novel, phenotype, unreported, in, prior, single, 'Id', knockout, studies])]). relacion([sujeto(['We', observe]), verbo([decreased]), complemento([cell, counts, in, the, bone, marrow, and, splenomegaly, to, dimensions, beyond, what, is, seen, in, single, 'Id', knockout, models])]). relacion([sujeto(['E47', protein, levels, were, elevated, in, 'Id', cDKO, bone, marrow, cell, 'isolates,', but]), verbo([decreased]), complemento([in, the, erythroid, lineage])]). relacion([sujeto(['Chromatin', immunoprecipitation, '(', 'ChIP)', studies]), verbo([reveal]), complemento([increased, occupancy, of, 'E47', and, 'GATA1', at, the, promoter, regions, of, 'β-globin', and, 'E2A'])]). relacion([sujeto(['Bone', marrow, transplantation, studies, highlight, the, importance, of, intrinsic, 'Id', signals, in]), verbo([maintaining]), complemento([hematopoietic, homeostasis, while, revealing, a, strong, extrinsic, influence, in, the, development, of, anemia])]). relacion([sujeto(['Together,', these, findings, demonstrate, that]), verbo([loss]), complemento([of, 'Id', compensation, leads, to, dysregulation, of, the, hematopoietic, transcriptional, network, and, multiple, defects, in, erythropoietic, development, in, adult, mice])]). relacion([sujeto(['Molecular', oxygen, sustains, aerobic, 'life,', but, it, also, serves, as, the, substrate, for, oxidative, 'stress,', which]), verbo([has]), complemento([been, associated, with, the, pathogenesis, of, disease, and, with, aging])]). relacion([sujeto(['Compared', with, mice, housed, in, normoxia, '(', 21, '%', 'O2),', reducing, ambient, oxygen, to, 10, '%', 'O2', '(', 'hypoxia)', resulted, in]), verbo([increased]), complemento([hematopoietic, stem, cell, '(', 'HSC)', function, as, measured, by, bone, marrow, '(', 'BM)', cell, engraftment, onto, lethally, irradiated, recipients])]). relacion([sujeto(['The', number, of, 'BM', 'c-Kit(+)Sca-1(+)Lin(-)', '(', 'KSL)', cells, as, well, as, the, number, of, cells, with, other, hematopoietic, stem, and, progenitor, cell, markers, were]), verbo([increased]), complemento([in, hypoxia, 'mice,', whereas, the, 'BM', 'cells\'', 'colony-forming', capacity, remained, unchanged])]). relacion([sujeto(['KSL', cells, from, hypoxia, mice, showed, a]), verbo([decreased]), complemento([level, of, oxidative, stress, and, increased, expression, of, transcription, factor, 'Gata1', and, cytokine, receptor, 'c-Mpl,', consistent, with, the, observations, of, increased, erythropoiesis, and, enhanced, 'HSC', engraftment])]). relacion([sujeto(['These', observations, demonstrate, the, benefit, of, a, hypoxic, 'HSC', niche, and]), verbo([suggest]), complemento([that, hypoxic, conditions, can, be, further, optimized, to, preserve, stem, cell, integrity, 'in vivo'])]). relacion([sujeto(['Increased', erythropoietic, activity, is]), verbo([required]), complemento([after, 'myelo-suppression', as, a, result, of, 'chemo-radio', therapies])]). relacion([sujeto(['These', results]), verbo([suggested]), complemento([that, 'ESAM', expression, in, hematopoietic, 'cells,', but, not, environmental, 'cells,', is, critical, for, hematopoietic, recovery])]). relacion([sujeto(['We', also]), verbo([found]), complemento([that, 5, -, 'FU', treatment, induces, the, 'up-regulation', of, 'ESAM', in, primitive, erythroid, progenitors, and, macrophages, that, do, not, express, 'ESAM', under, homeostatic, conditions])]). relacion([sujeto(['The', phenotypic, change, seen, in, macrophages, might, be, functionally]), verbo([involved]), complemento([in, the, interaction, between, erythroid, progenitors, and, their, niche, components, during, 'stress-induced', acute, erythropoiesis])]). relacion([sujeto(['However,', the, mechanisms, underlying, defective, erythropoiesis, in, leukemia]), verbo([have]), complemento([not, been, fully, elucidated])]). relacion([sujeto(['In', this, 'study,', we, demonstrated, that, insufficient, erythropoiesis, in, an, immunocompetent, acute, myeloid, leukemia, '(', 'AML)', murine, model, was, due, to, reduced, proliferation, of, megakaryocyte, erythroid, progenitors, and]), verbo([increased]), complemento([apoptosis, of, erythroblasts])]). relacion([sujeto(['Colony-forming', cell, assays, indicated, that, the, leukemic, bone, marrow, '(', 'BM)', plasma]), verbo([inhibited]), complemento([erythroid, colony, 'formation,', whereas, they, had, no, inhibitory, effect, on, other, types, of, colonies])]). relacion([sujeto(['CCL3']), verbo([inhibited]), complemento([erythroid, differentiation, of, hematopoietic, stem, 'cells,', common, myeloid, progenitors, and, especially, 'megakaryocytic-erythroid', progenitors])]). relacion([sujeto(['Mechanistically,', we, observed, an]), verbo([increase]), complemento([of, p38, phosphorylation, and, subsequent, downregulation, of, 'GATA1', after, 'CCL3', treatment])]). relacion([sujeto(['Therefore,', our, results, demonstrate, that, elevated, 'CCL3', in, the, leukemic, environment]), verbo([suppresses]), complemento([erythropoiesis, via, 'CCR1-p38', 'activation,', suggesting, a, novel, mechanism, for, the, erythroid, defects, observed, in, leukemia])]). relacion([sujeto(['The', 'expression,', function, and, therapeutic, significance, of, noncoding, 'RNAs', in, 'AEL']), verbo([have]), complemento([not, been, well, studied])]). relacion([sujeto(['Restoration', of, 'miR-23a,', -, 27, a, and, -, 24, expression]), verbo([induces]), complemento([apoptosis, and, 'erythropoiesis,', inhibits, adverse, growth, and, partly, relieves, the, leukemic, symptoms, of, 'AEL', patients])]). relacion([sujeto(['At', the, 'whole-genome', 'scale,', we, identify, that, 'miR-23a,', -, 27, a, and, -, 24, synergistically]), verbo([target]), complemento([multiple, members, of, the, oncogenic, 'gp130-JAK1-Stat3', 'pathway,', and, thus, reinforce, their, inhibition, on, the, cascade, to, regulate, cell, proliferation, and, apoptosis])]). relacion([sujeto(['Importantly,', 'Ruxolitinib,', a, 'JAK1', 'inhibitor,', could, rescue, the, phenotypic, changes]), verbo([induced]), complemento([by, 'miR-23a,', -, 27, a, and, -, 24, inhibitors])]). relacion([sujeto(['Furthermore,', 'miR-23a', 'cluster-mediated-inactivation', of, the, 'JAK1-Stat3', pathway]), verbo([promotes]), complemento([the, expression, and, activity, of, 'GATA1', via, inhibiting, 'PU'])]). relacion([sujeto(['Collectively,', we]), verbo([reveal]), complemento([an, important, regulatory, circuit, comprising, 'GATA1,', the, 'miR-23a', cluster, and, 'gp130-JAK1-Stat3', 'pathway,', that, synergistically, facilitates, apoptosis, and, erythropoiesis, and, restrains, adverse, 'proliferation,', indicating, the, therapeutic, significance, of, 'miR-23a,', -, 27, a, and, -, 24, for, 'AEL', treatment])]). relacion([sujeto(['DBA', is]), verbo([associated]), complemento([with, an, increased, risk, for, acute, myelogenous, leukemia, '(', 'AML),', myelodysplastic, syndrome, '(', 'MDS),', and, solid, tumors, including, osteogenic, sarcoma])]). relacion([sujeto(['Other']), verbo([causes]), complemento([of, bone, marrow, failure, '(', e])]). relacion([sujeto(['DBA']), verbo([has]), complemento([been, associated, with, pathogenic, variants, in, sixteen, genes, that, encode, ribosomal, proteins, and, in, 'GATA1', and, 'TSR2'])]). relacion([sujeto(['Chemotherapy', must, be, given, cautiously, as, it, may]), verbo([lead]), complemento([to, prolonged, cytopenia, and, subsequent, toxicities])]). relacion([sujeto(['Corticosteroid-related', side, effects, must, also, be, closely, 'monitored,', especially, as, related, to, risk, for, 'infection,', growth, 'retardation,', and]), verbo([loss]), complemento([of, bone, density, in, growing, children])]). relacion([sujeto(['Agents/circumstances', to, 'avoid:', 'Deferiprone', for, the, treatment, of, iron, 'overload,', which]), verbo([has]), complemento([led, to, severe, neutropenia, in, a, few, individuals, with, 'DBA;', infection, '(', especially, those, on, 'corticosteroids)'])]). relacion([sujeto(['Approximately', 40, '%', to, 45, '%', of, individuals, with, autosomal, dominant, 'DBA']), verbo([have]), complemento([inherited, the, pathogenic, variant, from, a, 'parent;', approximately, 55, '%', to, 60, '%', have, a, de, novo, pathogenic, variant])]). relacion([sujeto(['Each', child, of, an, individual, with, autosomal, dominant, 'DBA']), verbo([has]), complemento([a, 50, '%', chance, of, inheriting, the, pathogenic, variant])]). relacion([sujeto(['Women', heterozygous, for, a, 'GATA1', or, 'TSR2', pathogenic, variant]), verbo([have]), complemento([a, 50, '%', chance, of, transmitting, the, pathogenic, variant, in, each, 'pregnancy:', males, who, inherit, the, pathogenic, variant, will, be, 'affected;', females, who, inherit, the, pathogenic, variant, will, be, carriers, and, will, usually, not, be, affected])]). relacion([sujeto(['Carrier', testing, of, 'at-risk', female, relatives, is, possible, if, the, 'GATA1', or, 'TSR2', pathogenic, variant]), verbo([has]), complemento([been, identified, in, the, family])]). relacion([sujeto(['Prenatal', testing, for, pregnancies, at]), verbo([increased]), complemento([risk, is, possible, if, the, familial, pathogenic, variant, has, been, identified])]). relacion([sujeto(['Whole-exome', sequencing]), verbo([has]), complemento([been, incredibly, successful, in, identifying, causal, genetic, variants, and, has, revealed, a, number, of, novel, genes, associated, with, blood, and, other, diseases])]). relacion([sujeto(['Here', we, used, 'CRISPR/Cas9', genome, editing, to, interrogate, three, such, elements, harboring, mutations, in, human, erythroid, 'disorders,', which, in, all, cases, are, predicted, to, disrupt, a, canonical]), verbo([binding]), complemento([motif, for, the, hematopoietic, transcription, factor, 'GATA1'])]). relacion([sujeto(['Deletions', of, as, few, as, two, to, four, nucleotides, resulted, in, a, substantial]), verbo([decrease]), complemento(['(', &, 'gt;80%)', in, target, gene, expression])]). relacion([sujeto(['Isolated', deletions, of, the, canonical, 'GATA1']), verbo([binding]), complemento([motif, completely, abrogated, binding, of, the, cofactor, 'TAL1,', which, binds, to, a, separate, motif])]). relacion([sujeto(['Having', verified, the, functionality, of, these, three, 'GATA1', 'motifs,', we, demonstrate, strong, evolutionary, conservation, of, 'GATA1', motifs, in, regulatory, elements, proximal, to, other, genes, implicated, in, erythroid, 'disorders,', and, show, that]), verbo([targeted]), complemento([disruption, of, such, elements, results, in, altered, gene, expression])]). relacion([sujeto(['By', modeling, transcription, factor]), verbo([binding]), complemento(['patterns,', we, show, that, multiple, transcription, factors, are, associated, with, erythroid, gene, 'expression,', and, have, created, predictive, maps, modeling, putative, disruptions, of, their, binding, sites, at, key, regulatory, elements])]). relacion([sujeto(['Our', study]), verbo([provides]), complemento([insight, into, 'GATA1', transcriptional, activity, and, may, prove, a, useful, resource, for, investigating, the, pathogenicity, of, noncoding, variants, in, human, erythroid, disorders])]). relacion([sujeto(['The', most, common, subgroups, were, 'KMT2A', rearrangement, '(', 29, '%', ')', ',', normal, karyotype, '(', 15, '%', ')', ',', 'RUNX1-RUNX1T1', '(', 10, '%', ')', ',', deletions, of, 5, 'q,', 7, q, 'and/or', 17, p, '(', 9, '%', ')', ',', myeloid, leukaemia]), verbo([associated]), complemento([with, 'Down', syndrome, '(', 7, '%', ')', ',', 'PML-RARA', '(', 7, '%', ')', and, 'CBFB-MYH11', '(', 5, '%', ')'])]). relacion([sujeto(['Single', nucleotide, polymorphism, array, '(', 'SNP-A)', analysis, and, exon, sequencing, of, 100, 'genes,', performed, in, 52, and, 40, 'cases,', respectively, '(', 39, 'overlapping),', revealed, '≥1', aberration, in, 89, '%', ;, when, adding, cytogenetic, 'data,', this, frequency]), verbo([increased]), complemento([to, 98, '%'])]). relacion([sujeto(['Twenty-two', genes, were]), verbo([targeted]), complemento([by, focal, 'CNAs,', including, 'AEBP2', and, 'PHF6', deletions, and, genes, involved, in, 'AML-associated', gene, fusions])]). relacion([sujeto(['In', 'total,', 60, mutations, were]), verbo([found]), complemento([in, 30, 'genes,', primarily, those, encoding, signalling, proteins, '(', 47, '%', ')', ',', transcription, factors, '(', 25, '%', ')', ',', or, epigenetic, modifiers, '(', 13, '%', ')'])]). relacion([sujeto(['Here,', we, assessed, whether, shear, stress]), verbo([modulates]), complemento([trabeculation, to, influence, contractile, function])]). relacion([sujeto(['Subjecting', endothelial, cells, to, pulsatile, flow, in, the, presence, of, the, 'ADAM10', inhibitor, corroborated, shear, 'stress-activated', 'Notch', signaling, to]), verbo([modulate]), complemento([trabeculation])]). relacion([sujeto(['Transcription', factors, 'Runx1,', 'CBFβ', and, 'GATA1/2/3', play, essential, roles, in]), verbo([regulating]), complemento([hematopoietic, development, during, embryogenesis, of, vertebrate])]). relacion([sujeto(['In', previous, 'study,', the, orthologous, genes, of, 'Runt,', 'CBFβ', and, 'GATA1/2/3']), verbo([have]), complemento([been, identified, from, scallop, 'Chlamys', farreri, and, proved, to, have, conserved, function, in, regulating, hemocyte, production])]). relacion([sujeto([1, are, two, important, hematopoietic, transcription, factors, that, mutually]), verbo([inhibit]), complemento([each, other, in, progenitor, cells, to, guide, entrance, into, the, erythroid, or, myeloid, 'lineage,', respectively])]). relacion([sujeto([1, controls, its, own, expression, during, myelopoiesis, by]), verbo([binding]), complemento([to, the, distal, 'URE', 'enhancer,', whose, deletion, leads, to, acute, myeloid, leukemia, '(', 'AML)'])]). relacion([sujeto(['We', herein, present, evidence, that, 'GATA-1']), verbo([binds]), complemento([to, the, 'PU'])]). relacion([sujeto([1, gene, and]), verbo([inhibits]), complemento([its, expression, in, human, 'AML-erythroleukemias', '(', 'EL)'])]). relacion([sujeto(['Furthermore,', 'GATA-1', together, with, 'DNA', methyl, 'Transferase', 'I', '(', 'DNMT1)']), verbo([mediate]), complemento([repression, of, the, 'PU'])]). relacion([sujeto([1, gene]), verbo([involves]), complemento([both, 'DNA', methylation, at, the, 'URE', and, its, histone, 'H3', 'lysine-K9', methylation, and, deacetylation, as, well, as, the, 'H3K27', methylation, at, additional, 'DNA', elements, and, the, promoter])]). relacion([sujeto([1, gene, transcription, in, human, 'AML-EL']), verbo([mediated]), complemento([through, the, 'URE', represents, important, mechanism, that, contributes, to, 'PU'])]). relacion([sujeto(['Anemia', of, critical, illness, is, a, compounding, factor, in, burn, patients, that, necessitates, repeated, 'transfusions,', which, further]), verbo([increase]), complemento([their, susceptibility, to, infections, and, sepsis])]). relacion([sujeto(['In', addition, to, impaired, 'RBC', 'production,', burn, patients, are, prone, to, depletion, of, dendritic, cells, and, an]), verbo([increase]), complemento([in, deactivated, monocytes])]). relacion([sujeto(['We', hypothesized, in, a, mouse, model, of, burn, injury, that, an]), verbo([increase]), complemento([in, 'myeloid-specific', transcription, factor, 'V-maf', musculoaponeurotic, fibrosarcoma, oncogene, homolog, 'B', at, the, common, myeloid, progenitor, stage, steers, their, lineage, potential, away, from, the, megakaryocyte, erythrocyte, progenitor, production, and, drives, the, terminal, fate, of, common, myeloid, progenitors, to, form, macrophages, vs])]). relacion([sujeto(['Results', indicate, 'that,', even, though, burn, injury]), verbo([stimulated]), complemento([bone, marrow, hematopoiesis, by, increasing, multipotential, stem, cell, production, '(', 'Lin(neg)Sca1(pos)cKit(pos)),', the, bone, marrow, commitment, is, shifted, away, from, the, megakaryocyte, erythrocyte, progenitor, and, toward, granulocyte, monocyte, progenitors, with, corresponding, alterations, in, peripheral, blood, 'components,', such, as, 'hemoglobin,', 'hematocrit,', 'RBCs,', 'monocytes,', and, granulocytes])]). relacion([sujeto(['Furthermore,', 'burn-induced', 'V-maf', musculoaponeurotic, fibrosarcoma, oncogene, homolog, 'B', in, common, myeloid, progenitors]), verbo([acts]), complemento([as, a, transcriptional, activator, of, 'M-CSFR', and, a, repressor, of, transferrin, 'receptors,', promoting, macrophages, and, inhibiting, erythroid, differentiations, while, dictating, a, plasmacytoid, dendritic, cell, phenotype])]). relacion([sujeto(['Results', from, small, interfering, 'RNA', and, 'gain-of-function', '(', 'gfp-globin', transcription, factor, 1, 'retrovirus)', studies, indicate, that]), verbo([targeted]), complemento([interventions, to, restore, 'V-maf', musculoaponeurotic, fibrosarcoma, oncogene, homolog, 'B/globin', transcription, factor, 1, balance, can, mitigate, both, immune, imbalance, and, anemia, of, critical, illness])]). relacion([sujeto(['As', well, as, in, the]), verbo([arrest]), complemento([of, 'bleeding,', the, secreted, proteins, participate, in, wound, 'healing,', 'inflammation,', and, innate, immunity, while, in, pathology, they, may, be, actors, in, arterial, thrombosis, and, atherosclerosis, as, well, as, cancer, and, metastasis])]). relacion([sujeto(['For', a, long, 'time,', gray, platelet, syndrome, '(', 'GPS)']), verbo([has]), complemento([been, regarded, as, the, classic, inherited, platelet, disorder, caused, by, an, absence, of, 'α-granules', and, their, contents])]). relacion([sujeto(['Nevertheless,', many, phenotypic, differences, are]), verbo([associated]), complemento([with, mutations, in, these, genes])]). relacion([sujeto(['The', severity, of, clinical, manifestations, is, markedly, heterogeneous, among, 'patients;', and, interdependence, between, disease, severity, and, porphyrin, amount, in, the, tissues]), verbo([has]), complemento([been, pointed, out])]). relacion([sujeto(['A', more, pronounced, endogenous, production, of, porphyrins, concomitant, to, activation, of, 'ALAS2,', the, first, and, 'rate-limiting', of, the, haem, synthesis, enzymes, in, erythroid, 'cells,']), verbo([has]), complemento([also, been, reported])]). relacion([sujeto(['The', 'GATA', family, of, transcription, factors, consists, of, six, proteins, '(', 'GATA1-6)', which, are]), verbo([involved]), complemento([in, a, variety, of, physiological, and, pathological, processes])]). relacion([sujeto(['GATA1/2/3', are]), verbo([required]), complemento([for, differentiation, of, mesoderm, and, 'ectoderm-derived', 'tissues,', including, the, haematopoietic, and, central, nervous, system])]). relacion([sujeto(['Children', with, 'Down', syndrome, '(', 'DS)']), verbo([have]), complemento([a, markedly, increased, risk, of, leukemia])]). relacion([sujeto(['They', are, at, particular, risk, of, acute, megakaryoblastic, 'leukemia,', known, as, myeloid, leukemia]), verbo([associated]), complemento([with, 'DS', '(', 'ML-DS),', the, development, of, which, is, closely, linked, to, a, preceding, temporary, form, of, neonatal, leukemia, called, transient, abnormal, myelopoiesis, '(', 'TAM)'])]). relacion([sujeto(['Findings', from, recent, clinical, and, laboratory, studies]), verbo([suggest]), complemento([that, constitutional, trisomy, 21, and, 'GATA1', 'mutation(s)', cause, 'TAM,', and, that, additional, genetic, 'alteration(s)', including, those, in, epigenetic, regulators, and, signaling, molecules, are, involved, in, the, progression, from, 'TAM', to, 'ML-DS'])]). relacion([sujeto(['The', results]), verbo([suggested]), complemento([that, the, stem, cells, in, the, hematopoietic, tissue, of, 'Chinese', mitten, crab, 'E'])]). relacion([sujeto([&, 'nbsp;sinensis', were]), verbo([regulated]), complemento([by, transcriptional, and, humoral, factors, to, generate, hemocytes])]). relacion([sujeto(['These', small, 'non-coding', 'RNAs']), verbo([participate]), complemento([in, producing, and, maturing, 'erythrocytes,', expressing, hematopoietic, factors, and, regulating, expression, of, globin, genes, by, 'post-tran-', scriptional, gene, silencing])]). relacion([sujeto(['The', changes, in, expression, of, miRs, '(', 'miR-144/-320/-451/-503)', in, 'thalassemic/sickle', cells, compared, with, normal, erythrocytes, may]), verbo([cause]), complemento([clinical, severity])]). relacion([sujeto(['According', to, the, suppressive, effects, of, certain, miRs, '(', 'miR-15a/-16-1/-23a/-26b/-27a/-451)', on, a, number, of, transcription, factors, '[', myeloblastosis, oncogene, '(', 'MYB),', 'B-cell', lymphoma, 11, 'A', '(', 'BCL11A),', 'GATA1,', 'Krüppel-like', factor, 3, '(', 'KLF3)', and, specificity, protein, 1, '(', 'Sp1)]', during, β, globin, gene, 'expression,', 'It']), verbo([has]), complemento([been, possible, to, increasing, γ, globin, gene, expression, and, fetal, hemoglobin, '(', 'HbF)', production])]). relacion([sujeto(['However,', how, transcription, factors]), verbo([interact]), complemento([with, 'histone-modifying', enzymes, to, regulate, 'VEGF', transcription, and, tumor, angiogenesis, remains, unclear])]). relacion([sujeto(['Here,', we, show, that, transcription, factor, 'GATA1']), verbo([associates]), complemento([with, the, histone, methyltransferase, 'SET7', to, promote, 'VEGF', transcription, and, breast, tumor, angiogenesis])]). relacion([sujeto(['Using', chromatin, immunoprecipitation, 'assay,', we]), verbo([found]), complemento([that, 'GATA1', was, required, for, recruitment, of, 'SET7,', 'RNA', polymerase, 'II', and, transcription, factor, 'II', 'B', to, 'VEGF', core, promoter])]). relacion([sujeto(['GATA1']), verbo([enhanced]), complemento([breast, cancer, cell, '(', 'MCF7,', 'ZR75-1', and, 'MDA-MB-231)-secreted', 'VEGF', via, 'SET7,', which, promoted, vascular, endothelial, cell, '(', 'HUVEC)', 'proliferation,', migration, and, tube, formation])]). relacion([sujeto(['SET7', was]), verbo([required]), complemento([for, 'GATA1-induced', breast, tumor, angiogenesis, and, growth, in, nude, mice])]). relacion([sujeto(['Our', data]), verbo([provide]), complemento([novel, insights, into, 'VEGF', transcriptional, regulation, and, suggest, 'GATA1/SET7', as, cancer, therapeutic, targets])]). relacion([sujeto(['Children', with, 'Down', syndrome, '(', 'DS)']), verbo([have]), complemento([a, significantly, increased, risk, of, childhood, 'leukemia,', in, particular, acute, megakaryoblastic, leukemia, '(', 'AMKL)', and, acute, lymphoblastic, leukemia, '(', 'DS-ALL)'])]). relacion([sujeto(['A', 'pre-leukemia,', called, transient, myeloproliferative, disorder, '(', 'TMD),', characterised, by, a, 'GATA']), verbo([binding]), complemento([protein, 1, '(', 'GATA1)', 'mutation,', affects, up, to, 30, '%', of, newborns, with, 'DS'])]). relacion([sujeto(['This', model, represents, an, important, 'multi-step', process, of, 'leukemogenesis,', and, further, study, is]), verbo([required]), complemento([to, identify, therapeutic, targets, to, potentially, prevent, development, of, leukemia])]). relacion([sujeto(['Genetic', and, epigenetic, studies]), verbo([have]), complemento([revealed, likely, candidate, drivers, involved, in, development, of, 'ML-DS', and, 'DS-ALL'])]). relacion([sujeto(['We']), verbo([find]), complemento([that, enhancers, are, modulated, pervasively, and, direct, 'lineage-', and, 'stage-specific', transcription])]). relacion([sujeto(['Despite', indistinguishable, chromatin, 'features,', we]), verbo([reveal]), complemento([through, genomic, editing, the, functional, diversity, of, several, 'GATA', switch, enhancers, in, which, enhancers, with, opposing, functions, cooperate, to, coordinate, transcription])]). relacion([sujeto(['Thus,', 'genome-wide', enhancer, profiling, coupled, with, in, situ, enhancer, editing]), verbo([provide]), complemento([critical, insights, into, the, functional, complexity, of, enhancers, during, development])]). relacion([sujeto([1, and, 'GATA-1', as, 'lineage-specific', transcription, factors, '(', 'TF)', are]), verbo([expressed]), complemento([in, common, myeloid, progenitors])]). relacion([sujeto(['This', concept, in, transdifferentiation, approaches]), verbo([has]), complemento([not, been, well, considered, 'yet,', especially, in, intralineage, conversion, systems])]). relacion([sujeto([1, suppression]), verbo([induces]), complemento([monocyte, lineage, conversion, into, red, blood, 'cells,', a, combination, of, three, 'PU'])]). relacion([sujeto([1, gene, expression, and, generate, the, balance, in, favor, of, 'GATA-1', expression, to]), verbo([induce]), complemento([erythroid, differentiation])]). relacion([sujeto([1, expression, in, mRNA, level, was, significantly]), verbo([decreased]), complemento([until, 0.38, ±, 0.118, when, compared, to, untreated, monocytes, at, 72, &, 'nbsp;h', '(', p, value, '≤0'])]). relacion([sujeto(['Our', results]), verbo([suggest]), complemento([that, manipulating, the, ratio, of, the, two, 'TFs', in, bifurcation, differentiation, pathways, via, applying, siRNA, technology, can, possibly, change, the, 'cells\'', fate, as, a, safe, way, for, therapeutics, application])]). relacion([sujeto(['However,', engrafted, 'TAM-derived', cells, showed, the, emergence, of, divergent, subclones, with, another, 'GATA1', mutation, and, various, 'CNAs,', including, a, 16, q, deletion, and, 1, q, 'gain,', both, of, which, are, clinically]), verbo([associated]), complemento([with, 'ML-DS'])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, genetically, heterogeneous, subclones, with, various, 'leukemia-initiating', potentials, already, exist, in, the, neonatal, 'TAM', 'phase,', and, that, 'ML-DS', may, develop, from, a, pool, of, such, minor, clones, through, clonal, selection])]). relacion([sujeto(['Our', xenograft, model, could, be, a, valuable, tool, for]), verbo([gained]), complemento([insight, into, the, processes, underlying, leukemogenesis])]). relacion([sujeto(['We', show, that, '(', 'i)', this, constellation, of, hematopoietic, abnormalities, was, due, to, a, germline, mutation, within, the, 5, '\'', untranslated, region, '(', 5, '\'', 'UTR)', of, globin, transcription, factor, 1, '(', 'GATA1);', '(', 'ii)', the, mutation, impaired, a, 5, '\'', 'UTR', 'GATA1', splicing, 'site,', with]), verbo([promoted]), complemento([production, of, the, shortened, 'GATA1', isoform, lacking, the, 'N-terminus;', and, '(', 'iii)', expression, of, the, 'GATA1', 'N-terminus', is, restricted, to, erythroblasts, and, megakaryocytes, in, normal, 'marrow,', consistent, with, the, 'patient\'s', abnormal, erythropoiesis, and, megakaryopoiesis])]). relacion([sujeto(['Our', findings]), verbo([provide]), complemento([insights, into, the, clinically, relevant, in, vivo, function, of, the, 'N-terminal', domain, of, 'GATA1', in, human, hematopoiesis])]). relacion([sujeto(['The', combination, of, 'ETV2', and, 'GATA1', or, 'GATA2', 'TFs', is, used, to]), verbo([induce]), complemento(['HE', with, 'pan-myeloid', 'potential,', while, a, combination, of, 'GATA2', and, 'TAL1', transcription, factors, allows, for, the, production, of, 'HE', with, erythroid, and, megakaryocytic, potential])]). relacion([sujeto(['The', addition, of, 'LMO2', to, 'GATA2', and, 'TAL1', combination, substantially, accelerates, differentiation, and]), verbo([increases]), complemento([erythroid, and, megakaryocytic, cells, production])]). relacion([sujeto(['This', method]), verbo([provides]), complemento([an, efficient, and, rapid, means, of, 'HE', induction, from, hPSCs, and, allows, for, the, observation, of, the, 'endothelial-hematopoietic', transition, in, a, culture, dish])]). relacion([sujeto(['SCUBE1', '(', 'S1),', a, secreted, and, 'membrane-bound', 'glycoprotein,']), verbo([has]), complemento([a, modular, protein, structure, composed, of, an, 'N-terminal', signal, peptide, sequence, followed, by, nine, epidermal, growth, factor, '(', 'EGF)-like', 'repeats,', a, spacer, region, and, three, 'cysteine-rich', '(', 'CR)', motifs, with, multiple, potential, 'N-linked', glycosylation, 'sites,', and, one, 'CUB', domain, at, the, 'C-terminus'])]). relacion([sujeto(['Soluble', 'S1', is, a, biomarker, of, platelet, activation, but, an, active, participant, of, thrombosis, via, its, adhesive, 'EGF-like', 'repeats,', whereas, its, 'membrane-associated', form]), verbo([acts]), complemento([as, a, bone, morphogenetic, protein, '(', 'BMP)', 'co-receptor', in, promoting, 'BMP', signal, activity])]). relacion([sujeto(['In', the, present, 'study,', molecular, mapping, analysis, identified, a, polycationic, segment, '(', amino, acids, 501, -, 550, ')', in, the, spacer, region]), verbo([required]), complemento([for, its, membrane, tethering, via, electrostatic, interactions, possibly, with, the, anionic, heparan, sulfate, proteoglycans])]). relacion([sujeto(['We', describe, novel, mechanisms, in]), verbo([targeting]), complemento(['S1', to, the, plasma, membrane, and, demonstrate, that, 'N-glycans', are, required, for, 'S1', functions, during, primitive, haematopoiesis, in, zebrafish])]). relacion([sujeto(['Metal', 'ion-containing', macromolecules]), verbo([have]), complemento([fundamental, roles, in, essentially, all, biological, processes, throughout, the, evolutionary, tree])]). relacion([sujeto(['To', meet, the, intense, demand, for, hemoglobin, assembly, in, red, blood, 'cells,', the, cell, 'type-specific', factor, 'GATA-1']), verbo([activates]), complemento([transcription, of, 'Alas2,', encoding, the, 'rate-limiting', enzyme, in, heme, 'biosynthesis,', 5, -, aminolevulinic, acid, 'synthase-2', '(', 'ALAS-2)'])]). relacion([sujeto(['Bypassing', 'ALAS-2', function, in, 'Alas2', cis, 'element-mutant', cells, by]), verbo([providing]), complemento([its, catalytic, product, 5, -, aminolevulinic, acid, rescues, heme, biosynthesis, and, the, 'GATA-1-dependent', genetic, network])]). relacion([sujeto(['Through', this, dual, 'mechanism,', heme, and, a, master, regulator, collaborate, to, orchestrate, a, cell, 'type-specific', transcriptional, program, that]), verbo([promotes]), complemento([cellular, differentiation])]). relacion([sujeto(['Here,', we, show, that, erythropoietin]), verbo([activates]), complemento(['AKT,', which, phosphorylates, 'GATA-1', at, 'Ser310,', thereby, increasing, 'GATA-1', affinity, for, 'FOG-1'])]). relacion([sujeto(['In', 'turn,', 'FOG-1', displaces, 'pRb/E2F-2', from, 'GATA-1,', ultimately]), verbo([releasing]), complemento(['free,', proproliferative, 'E2F-2'])]). relacion([sujeto(['Mice', bearing, a, 'Gata-1(S310A)', mutation, suffer, from, fatal, anemia, when, a, compensatory, pathway, for, 'E2F-2', production]), verbo([involving]), complemento(['insulin-like', growth, 'factor-1', '(', 'IGF-1)', signaling, is, simultaneously, abolished])]). relacion([sujeto(['In', the, context, of, the, 'GATA-1(V205G)', mutation, resulting, in, lethal, 'anemia,', we, show, that, the, 'Ser310', cannot, be]), verbo([phosphorylated]), complemento([and, that, constitutive, phosphorylation, at, this, position, restores, partial, erythroid, differentiation])]). relacion([sujeto(['Acute', myeloid, leukemia, '(', 'AML)', 1, -, 'Evi-1', is, a, chimeric, gene, generated, by, the, t, '(', 3, ;, 21, ')', '(', 'q26;', 'q22)', 'translocation,', which]), verbo([leads]), complemento([into, malignant, transformation, of, hematopoietic, stem, cells, by, unclear, mechanisms])]). relacion([sujeto(['This', in, vivo, study, aimed, to, establish, a, stable, line, of, zebrafish]), verbo([expressing]), complemento([the, human, 'RUNX1-Evi-1', fusion, gene, under, the, control, of, a, heat, 'stress-inducible', bidirectional, 'promoter,', and, investigate, its, roles, in, hematopoiesis, and, hematologic, malignancies])]). relacion([sujeto(['Consequently,', primitive, hematopoiesis, was]), verbo([enhanced]), complemento([by, upregulation, of, gata2, and, 'scl,', while, erythropoiesis, was, downregulated, due, to, the, suppression, of, gata1])]). relacion([sujeto([1, ',', but, it, was]), verbo([inhibited]), complemento([along, with, the, low, expression, of, mpo])]). relacion([sujeto(['Microarray', analysis, demonstrated, that, 'RUNX1-Evi-1', not, only, upregulated, 'proteasome,', cell, 'cycle,', 'glycolysis/gluconeogenesis,', tyrosine, 'metabolism,', drug, 'metabolism,', and, 'PPAR', 'pathway,', but, also]), verbo([suppressed]), complemento([transforming, growth, factor, 'β,', 'Jak-STAT,', 'DNA', 'replication,', mismatch, 'repair,', p53, 'pathway,', 'JNK', signaling, 'pathway,', and, nucleotide, excision, repair])]). relacion([sujeto(['Factors', in, cell, proliferation, were, obviously]), verbo([suppressed]), complemento([after, 3, -, day, treatment, with, histone, deacetylase, 'inhibitor,', valproic, acid])]). relacion([sujeto(['Accordingly,', higher, proportion, of, 'G1']), verbo([arrest]), complemento([and, apoptosis, were, manifested, by, the, propidium, iodide, staining])]). relacion([sujeto(['RUNX1-Evi-1', may]), verbo([promote]), complemento([proliferation, and, apoptosis, resistance, of, primitive, hematopoietic, 'cell,', and, inhibit, the, differentiation, of, myeloid, cells, with, the, synergy, of, different, pathways, and, factors])]). relacion([sujeto(['VPA', may, be, a, promising, choice, in, the, molecular]), verbo([targeting]), complemento([therapy, of, 'RUNX1-Evi-1-related', leukemia])]). relacion([sujeto(['Recent']), verbo([reports]), complemento([of, recurrent, mutations, in, childhood, acute, myeloid, leukemia, '(', 'AML)', have, identified, potential, targets, for, new, therapeutic, strategies])]). relacion([sujeto(['A', mutation, in, 'GATA1,', common, in, 'AML', of, 'Down', syndrome, '(', 'ML-DS),', renders, cells, more, susceptible, to, cytarabine, and, 'anthracyclines,', thus, permitting]), verbo([targeted]), complemento([dose, reductions, to, preserve, high, survival, rates, while, reducing, toxicity])]). relacion([sujeto(['The', preclinical, and, clinical, data]), verbo([providing]), complemento([a, rationale, for, testing, in, children, of, specific, agents, in, children, is, discussed])]). relacion([sujeto(['Whether', the, expression, of, a, potential]), verbo([target]), complemento([is, sufficient, to, predict, response, to, a, targeted, therapy, is, an, open, question, in, childhood, 'AML'])]). relacion([sujeto(['Development', of, clinical, trials, to, evaluate]), verbo([targeted]), complemento([therapies, in, small, molecularly, defined, subsets, of, 'AML', will, be, the, next, great, challenge, for, all, cooperative, groups, in, 'North', 'America', and, 'Europe'])]). relacion([sujeto(['RBM15,', an, 'RNA']), verbo([binding]), complemento(['protein,', determines, 'cell-fate', specification, of, many, tissues, including, blood])]). relacion([sujeto(['We', demonstrate, that, 'RBM15', is, methylated, by, protein, arginine, methyltransferase, 1, '(', 'PRMT1)', at, residue, 'R578,']), verbo([leading]), complemento([to, its, degradation, via, ubiquitylation, by, an, 'E3', ligase, '(', 'CNOT4)'])]). relacion([sujeto(['At', the, molecular, 'level,', 'RBM15']), verbo([binds]), complemento([to, 'pre-messenger', 'RNA', intronic, regions, of, genes, important, for, megakaryopoiesis, such, as, 'GATA1,', 'RUNX1,', 'TAL1', and, 'c-MPL'])]). relacion([sujeto(['Furthermore,', preferential]), verbo([binding]), complemento([of, 'RBM15', to, specific, intronic, regions, recruits, the, splicing, factor, 'SF3B1', to, the, same, sites, for, alternative, splicing])]). relacion([sujeto(['Therefore,', 'PRMT1']), verbo([regulates]), complemento([alternative, 'RNA', splicing, via, reducing, 'RBM15', protein, concentration])]). relacion([sujeto(['It', is, usually]), verbo([caused]), complemento([by, promoter, variants, or, large, deletions, affecting, the, human, fetal, globin, '(', 'HBG1', and, 'HBG2)', genes])]). relacion([sujeto([-, 158, 'C', &, 'gt;', 'T', favors, a, higher, 'Hb', 'F', 'response,', while, it]), verbo([has]), complemento([little, effect, in, healthy, individuals])]). relacion([sujeto(['We', analyzed, a, previously]), verbo([reported]), complemento([deletion, residing, in, the, promoter, region, of, the, 'HBG1', gene, '(', 'HBG1:', g])]). relacion([sujeto(['Our', results, indicate, that, this, deletion, is, responsible, for]), verbo([decreased]), complemento(['HBG1', gene, expression])]). relacion([sujeto([-, 225, '_-222delAGCA', deletion, creates, additional, transcriptional, 'factors\'']), verbo([binding]), complemento(['sites,', 'which,', we, 'propose,', bind, a, transcriptional, 'repressor,', thus, decreasing, the, 'HBG1', gene, promoter, activity])]). relacion([sujeto(['These', results, are, consistent, with, in, silico, 'analysis,', which, indicated, that, this, deletion, creates, a]), verbo([binding]), complemento([site, for, 'GATA1,', known, to, be, a, repressor, of, the, 'γ-globin', gene, expression])]). relacion([sujeto(['Benzidine', staining, showed, that, simulated, microgravity]), verbo([inhibited]), complemento([erythroid, differentiation, of, 'K562', cells])]). relacion([sujeto(['K562', cells, treated, with, 'Hemin', presented, with]), verbo([increased]), complemento([mRNA, expression, of, 'GATA-1', and, reduced, 'GATA-2', and, 'Ets-1', mRNA, expressions])]). relacion([sujeto(['Exposure', to, simulated, microgravity]), verbo([caused]), complemento([decreased, fluorescence, intensities, of, cytoskeletal, filament, 'F-actin,', 'β-tubulin', and, vimentin, in, the, cells])]). relacion([sujeto(['Simulated', microgravity]), verbo([inhibits]), complemento([erythroid, differentiation, of, 'K562', cells, possibly, by, causing, cytoskeleton, damages, to, result, in, 'down-regulation', of, 'GATA-1', and, 'up-regulation', of, 'GATA-2', and, 'Ets-1', expressions])]). relacion([sujeto(['To', answer, these, 'questions,', we, screened, for, zebrafish, mutants, that]), verbo([have]), complemento([defects, in, the, hemangioblast, expression, of, 'Gata1,', which, is, never, expressed, in, endothelial, progenitors])]). relacion([sujeto(['Our', results]), verbo([suggest]), complemento([that, the, 'LSD1-dependent', shutdown, of, 'Etv2', gene, expression, may, be, a, significant, event, required, for, hemangioblasts, to, initiate, hematopoietic, differentiation])]). relacion([sujeto(['ChIP-seq', experiments, are, widely, used, to, detect, and, study, 'DNA-protein', 'interactions,', such, as, transcription, factor]), verbo([binding]), complemento([and, chromatin, modifications])]). relacion([sujeto(['We', hypothesize, that, statistically, significant, differences, in, peak, shape, might]), verbo([have]), complemento([a, functional, role, and, a, biological, meaning])]). relacion([sujeto(['Our', study, demonstrates, that, 'ChIP-seq', profiles, include, information, regarding, the]), verbo([binding]), complemento([of, other, proteins, beside, the, one, used, for, precipitation])]). relacion([sujeto(['In', 'particular,', peak, shape]), verbo([provides]), complemento([new, insights, into, cooperative, transcriptional, regulation, and, is, correlated, to, gene, expression])]). relacion([sujeto(['Erythroid', development, and, differentiation, from, multiprogenitor, cells, into, red, blood, cells]), verbo([requires]), complemento([precise, transcriptional, regulation])]). relacion([sujeto(['Key', erythroid, transcription, 'factors,', 'GATA1', and, 'TAL1,', 'cooperate,', along, with, other, 'proteins,', to]), verbo([regulate]), complemento([many, aspects, of, this, process])]). relacion([sujeto(['How', 'GATA1', and, 'TAL1', are, juxtaposed, along, the, 'DNA', and, their, cognate, 'DNA']), verbo([binding]), complemento([site, across, the, mouse, genome, remains, unclear])]). relacion([sujeto(['Two', complementary, 'methods,', 'MultiGPS', and, peak, 'pairing,', were, used, to, determine, 'high-confidence']), verbo([binding]), complemento([locations, by, 'ChIP-exo'])]). relacion([sujeto(['Of', 'these,', '∼4,000', locations, were]), verbo([bound]), complemento([by, both, 'GATA1', and, 'TAL1'])]). relacion([sujeto(['Thalidomide', was, shown, to]), verbo([stimulate]), complemento([erythropoiesis, and, increase, hemoglobin, level, in, multiple, myeloma, 'patients,', but, way, of, such, activity, remains, unclear])]). relacion([sujeto(['The', aim, of, the, study, was, to, investigate, the, mechanisms, of, thalidomide]), verbo([stimulating]), complemento([effect, on, erythroid, differentiation])]). relacion([sujeto(['Our', results]), verbo([suggest]), complemento([that, thalidomide, enhances, expression, of, 'STAT5', in, response, of, erythroid, cells, to, erythropoietin, and, as, a, result, of, caspase, 3, suppression])]). relacion([sujeto(['Moreover', it, may, exert, inhibitory, effect, on, an, external, pathway, of, caspases, activation, with, consequent]), verbo([decreased]), complemento([degradation, of, 'GATA-1', transcription, factor, by, downstream, caspases])]). relacion([sujeto(['Here', we, show, that, the, 'γ-secretase']), verbo([activating]), complemento([protein, '(', 'GSAP),', a, key, enzyme, in, 'amyloidogenesis,', is, increased, in, 'DS', brains, and, specifically, regulated, at, the, transcriptional, level, by, 'GATA1', transcription, factor])]). relacion([sujeto(['The', discovery, of, this, novel, pathway]), verbo([has]), complemento([translational, implications, for, 'DS,', because, pharmacological, inhibition, of, 'GSAP', is, an, attractive, and, viable, 'Aβ-lowering', therapeutic, strategy, for, this, disorder])]). relacion([sujeto([1]), verbo([bind]), complemento([in, vitro, and, in, vivo, the, proximal, promoter, region, of, the, 'RPS19', gene, which, is, frequently, mutated, in, 'Diamond-Blackfan', 'Anemia'])]). relacion([sujeto([1, gene]), verbo([targets]), complemento([in, mouse, and, human, erythroid, 'cells,', with, 'GATA1', binding, showing, an, association, with, higher, ribosomal, protein, gene, expression, levels, during, terminal, erythroid, differentiation, in, human, and, mouse])]). relacion([sujeto(['Our', results]), verbo([suggest]), complemento([that, 'RP', gene, expression, and, hence, balanced, ribosome, biosynthesis, may, be, specifically, and, selectively, regulated, by, lineage, specific, transcription, factors, during, 'hematopoiesis,', a, finding, which, may, be, clinically, relevant, to, ribosomopathies])]). relacion([sujeto(['The', spleen, from, 'PMF', patients, contains]), verbo([increased]), complemento([numbers, of, hematopoietic, stem, cells, '(', 'HSC)', and, megakaryocytes, '(', 'MK)'])]). relacion([sujeto(['These', 'MK']), verbo([express]), complemento([high, levels, of, 'P-selectin', '(', 'P-sel)', 'that,', by, triggering, neutrophil, 'emperipolesis,', may, cause, 'TGF-β', release, and, disease, progression])]). relacion([sujeto(['This', hypothesis, was, tested, by, deleting, the, 'P-sel', gene, in, the, myelofibrosis, mouse, model, carrying, the, hypomorphic, 'Gata1(low)', mutation, that]), verbo([induces]), complemento([megakaryocyte, abnormalities, that, recapitulate, those, observed, in, 'PMF'])]). relacion([sujeto(['P-sel(null)', 'Gata1(low)', mice, survived, splenectomy, and, lived, 3, months, longer, than, 'P-sel(WT)', 'Gata1(low)', littermates, and]), verbo([expressed]), complemento([limited, fibrosis, and, osteosclerosis, in, the, marrow, or, splenomegaly])]). relacion([sujeto(['Spleens,', but, not, 'marrow,', of, 'Gata1(low)', mice, contained, numerous, 'cKIT(pos)']), verbo([activated]), complemento(['fibrocytes,', probably, of, dendritic, cell, 'origin,', whose, membrane, protrusions, interacted, with, 'MK', establishing, niches, hosting, immature, 'cKIT(pos)', hematopoietic, cells])]). relacion([sujeto(['These']), verbo([activated]), complemento([fibrocytes, were, not, detected, in, spleens, from, 'P-sel(null)', 'Gata1(low)', or, 'TGF-β-inhibited', 'Gata1(low)', littermates, and, were, observed, in, 'spleen,', but, not, in, 'marrow,', from, 'PMF', patients])]). relacion([sujeto(['Therefore,', in, 'Gata1(low)', 'mice,', and, possibly, in, 'PMF,', abnormal, 'P-sel', expression, in, 'MK', may]), verbo([mediate]), complemento([the, pathological, cell, interactions, that, increase, 'TGF-β', content, in, 'MK', and, favor, establishment, of, a, microenvironment, that, supports, 'myelofibrosis-related', 'HSC', in, spleen])]). relacion([sujeto(['Erythropoietin', is, a, glycoprotein, hormone, that]), verbo([acts]), complemento([principally, on, erythroid, 'progenitors,', stimulating, their, 'survival,', proliferation, and, differentiation])]). relacion([sujeto(['Recombinant', human, erythropoietin, '(', 'rhEPO)']), verbo([has]), complemento([been, widely, used, in, medicine, to, treat, anemia, and, it, is, one, of, the, 'best-selling', biotherapeutics, worldwide])]). relacion([sujeto(['The', recombinant, 'molecule,', industrially, produced, in, 'CHO', 'cells,']), verbo([has]), complemento([the, same, amino, acid, sequence, of, endogenous, human, 'erythropoietin,', but, differs, in, the, glycosylation, pattern])]). relacion([sujeto(['A', significant]), verbo([increase]), complemento([in, 'Stat5', phosphorylation, was, also, assessed, in, embryos, treated, with, rhEPOs, when, compared, with, the, negative, controls])]). relacion([sujeto(['Live', imaging, in, tg, '(', 'kdrl:EGFP;', 'gata1:ds-red)', 'embryos,', 'o-dianisidine', positive, area, quantification, and, cyanomethemoglobin, content, quantification, revealed, a, 1.8, ±, 0.3, fold]), verbo([increase]), complemento([of, erythrocytes, amount, in, embryos, treated, with, rhEPOs, when, compared, with, the, negative, controls])]). relacion([sujeto(['Finally,', we, verified, that, recombinant, human, erythropoietins, did, not]), verbo([cause]), complemento([any, inflammatory, response, in, the, treated, embryos])]). relacion([sujeto(['In', recent, 'years,', several, lines, of, evidence]), verbo([suggested]), complemento([that, certain, 'nutrients,', vitamins, and, flavonoids, may, have, important, roles, in, controlling, the, stem, cell, fate, decision, by, maintaining, their, 'self-renewal', or, stimulating, the, 'lineage-specific', differentiation])]). relacion([sujeto(['Oleuropein', and, the, combination, of, the, three, compounds]), verbo([enhanced]), complemento([the, differentiation, of, 'CD34+', cells, into, myelomonocytic, cells, and, lymphocytes, progenitors, and, inhibited, the, commitment, to, megakaryocytic, and, erythroid, lineages])]). relacion([sujeto(['Treatment', with, 'Lut7G']), verbo([stimulated]), complemento([both, the, erythroid, and, the, myeloid, 'differentiation,', while, treatment, with, 'Api7G', specifically, induced, the, differentiation, of, 'CD34+', cells, towards, the, erythroid, lineage, and, inhibited, the, myeloid, differentiation])]). relacion([sujeto(['Erythroid', differentiation]), verbo([induced]), complemento([by, 'Api7G', and, 'Lut7G', treatments, was, confirmed, by, the, increase, in, hemoglobin, genes, expressions, '(', 'α-hemoglobin,', 'β-hemoglobin', and, 'γ-hemoglobin)', and, erythroid, transcription, factor, 'GATA1', expression])]). relacion([sujeto(['As', revealed, by, microarray, 'analysis,', the, mechanisms, underlying, the, erythroid, 'differentiation-inducing', effect, of, 'Api7G', on, hematopoietic, stem, cells]), verbo([involves]), complemento([the, activation, of, 'JAK/STAT', signaling, pathway])]). relacion([sujeto(['TGF-β1']), verbo([has]), complemento([been, reported, to, suppress, 'FcεRI', and, stem, cell, factor, receptor, 'c-Kit', expression, on, mast, cell, surfaces, and, to, suppress, mast, cell, activation, induced, by, 'cross-linking', of, 'FcεRI'])]). relacion([sujeto(['However,', the, molecular, mechanism, by, which, these, expressions, and, activation, are]), verbo([suppressed]), complemento([by, 'TGF-β1', remains, unclear])]). relacion([sujeto(['In', this, 'study,', we]), verbo([found]), complemento([that, the, expression, of, 'Ets', homologous, factor, '(', 'Ehf),', a, member, of, the, 'Ets', family, transcriptional, 'factors,', is, upregulated, by, 'TGF-β/Smad', signaling, in, mouse, bone, 'marrow-derived', mast, cells, '(', 'BMMCs)'])]). relacion([sujeto(['Additionally,', forced, expression, of, 'Ehf']), verbo([suppressed]), complemento(['FcεRI-mediated', degranulation, and, cytokine, production])]). relacion([sujeto(['Ehf']), verbo([inhibited]), complemento([the, promoter, activity, of, genes, encoding, 'FcεRIα,', 'FcεRIβ,', and, 'c-Kit', by, binding, to, these, gene, promoters])]). relacion([sujeto(['Furthermore,', the, mRNA, levels, of, 'Gata1,', 'Gata2,', and, 'Stat5b', were, lower, in, 'BMMCs', stably]), verbo([expressing]), complemento(['Ehf', compared, with, control, cells])]). relacion([sujeto(['Because', 'GATA-1', and, 'GATA-2', are, positive, regulators, of, 'FcεRI', and, 'c-Kit', 'expression,']), verbo([decreased]), complemento([expression, of, 'GATAs', may, be, also, involved, in, the, reduction, of, 'FcεRI', and, 'c-Kit', expression])]). relacion([sujeto(['In', 'part,', mast, cell, response, to, 'TGF-β1', was, mimicked, by, forced, expression, of, 'Ehf,']), verbo([suggesting]), complemento([that, 'TGF-β1', suppresses, 'FcεRI', and, 'c-Kit', expression, and, suppresses, 'FcεRI-mediated', activation, through, upregulation, of, 'Ehf'])]). relacion([sujeto(['In', a, silico, 'analysis,', we, identify, four, 'GATA-1', putative]), verbo([binding]), complemento([sites, in, 'Nanog', proximal, promoter])]). relacion([sujeto(['Mutation', studies]), verbo([reveal]), complemento([that, one, of, the, four, putative, binding, sites, counts, for, 'GATA-1', repressing, 'Nanog', promoter, activity])]). relacion([sujeto(['Direct']), verbo([binding]), complemento([of, 'GATA-1', on, 'Nanog', proximal, promoter, is, confirmed, by, electrophoretic, mobility, shift, assay, and, chromatin, immunoprecipitation])]). relacion([sujeto(['Our', data]), verbo([provide]), complemento([new, insights, into, the, expanded, regulatory, circuitry, that, coordinates, 'Nanog', expression])]). relacion([sujeto(['To', elucidate, the, 'evo-devo', mechanisms, underpinning, the]), verbo([suppressed]), complemento([erythropoiesis, in, the, 'icefish,', we, conducted, comparative, studies, on, the, transcriptomes, and, microRNAomes, of, the, primary, haematopoietic, tissues, between, an, icefish, '(', 'Chionodraco', 'hamatus)', and, two, 'red-blooded', notothenioids, '(', 'Trematomus', bernacchii, and, 'Gymnodraco', 'acuticeps)'])]). relacion([sujeto(['Experimental', verification, showed, that, erythropoietic, suppression, in, the, icefish, may, be, attributable, to, the, upregulation, of, 'TGF-β', 'signalling,', which, coincides, with, reductions, in, multiple, transcription, factors, essential, for, erythropoiesis, and, the, upregulation, of, hundreds, of, 'microRNAs,', the, majority, '(', &, 'gt;', 80, '%', ')', of, which, potentially]), verbo([target]), complemento([erythropoiesis, regulating, factors])]). relacion([sujeto(['Codon', substitution, analyses, of, the, genes, of, the, 'TGF-β', superfamily, revealed, signs, of, positive, selection, in, 'TGF-β1', and, endoglin, in, the, lineages]), verbo([leading]), complemento([to, 'Antarctic', notothenioids])]). relacion([sujeto(['Most', affected, patients]), verbo([have]), complemento([heterozygous, loss, of, function, mutations, in, ribosomal, protein, genes, but, the, pathogenic, mechanism, is, still, unknown])]). relacion([sujeto(['We', generated]), verbo([induced]), complemento([pluripotent, stem, cells, from, 'DBA', patients, carrying, 'RPS19', or, 'RPL5', mutations])]). relacion([sujeto(['Expression', of, 'TGFβ']), verbo([target]), complemento(['genes,', such, as, 'TGFBI,', 'BAMBI,', 'COL3A1', and, 'SERPINE1', was, significantly, increased, in, the, 'DBA', iPSCs])]). relacion([sujeto(['We', quantified, intermediates, in, canonical, and, 'non-canonical', 'TGFβ', pathways, and, observed, a, significant]), verbo([increase]), complemento([in, the, levels, of, the, 'non-canonical', pathway, mediator, 'p-JNK', in, the, 'DBA', iPSCs])]). relacion([sujeto(['Surprisingly,']), verbo([nuclear]), complemento([levels, of, 'SMAD4,', a, mediator, of, canonical, 'TGFβ', 'signaling,', were, decreased, in, 'DBA', cells, due, to, increased, proteolytic, turnover])]). relacion([sujeto(['We', also, observed, the, 'up-regulation', of, 'TGFβ1R,', 'TGFβ2,', 'CDKN1A', and, 'SERPINE1', 'mRNA,', and, the, significant]), verbo([decrease]), complemento([of, 'GATA1', mRNA, in, the, primitive, multilineage, progenitors])]). relacion([sujeto(['Although', 'Down', syndrome, '(', 'DS)', patients]), verbo([have]), complemento([a, higher, risk, of, developing, transient, myeloproliferative, disorder, '(', 'TMD)', and, acute, 'leukemia,', very, little, data, is, available, on, 'long-term', outcome, in, 'Taiwanese', patients])]). relacion([sujeto(['In', 25, consecutive, 'DS', patients, with, 'TMD', or, 'AL', enrolled, from, 1990, to, 2012, ',', clinical, manifestations, and, treatment, protocols, were, investigated, and, 'GATA1', '(', 'GATA']), verbo([binding]), complemento([protein, 1, ')', mutations, were, identified])]). relacion([sujeto(['With', modification, of, the, treatment, strategy, in, 2008, ',', 'OS']), verbo([increased]), complemento([in, 'Taiwan'])]). relacion([sujeto(['Improvements', in, the, accuracy, of, diagnosing, 'AMegL', as, well, as, interest, in, the, molecular, analysis, of, leukemias]), verbo([have]), complemento([led, to, an, increased, amount, of, data, available, on, this, rare, 'AML', subtype])]). relacion([sujeto(['In', this, 'review,', we, will, analyze, the, diverse, molecular, features, unique, to, 'AMegL', and, how, they]), verbo([have]), complemento([influenced, the, development, of, novel, treatment, 'strategies,', including, polyploidization])]). relacion([sujeto(['The', papulovesicular, eruption, of, 'TMD']), verbo([provides]), complemento([an, important, clue, to, the, diagnosis])]). relacion([sujeto(['In', 'contrast,', 'AMKL', rarely]), verbo([has]), complemento([associated, cutaneous, findings])]). relacion([sujeto(['We']), verbo([report]), complemento([the, case, of, a, 22, -, 'month-old', child, with, trisomy, 21, who, presented, with, the, acute, onset, of, diffusely, scattered, and, crusted, 'papules,', 'plaques,', and, vesicles])]). relacion([sujeto(['Two', weeks, later]), verbo([he]), complemento([was, reassessed, and, found, to, have, a, population, of, blasts, on, repeat, 'CBC'])]). relacion([sujeto(['Subsequent', evaluation, ultimately]), verbo([led]), complemento([to, a, diagnosis, of, 'AMKL'])]). relacion([sujeto(['This', is, the, first]), verbo([reported]), complemento([case, of, a, cutaneous, eruption, in, a, young, child, with, 'Down', syndrome, and, transformed, 'AMKL'])]). relacion([sujeto(['CBFA2T3-GLIS2', is, the, most, frequent, chimeric, oncogene, identified, to, date, in, this, subset, of, patients, and]), verbo([confers]), complemento([a, poor, prognosis])]). relacion([sujeto(['A', significant, proportion, of, recurrent, respiratory, papillomatosis, '(', 'RRP)', is]), verbo([caused]), complemento([by, human, papillomavirus, type, 6, '(', 'HPV-6)'])]). relacion([sujeto(['Differences', in, putative, 'TFs']), verbo([binding]), complemento([sites, among, variants, were, revealed, using, the, 'TRANSFAC', database])]). relacion([sujeto(['Chromatin', immunoprecipation, '(', 'CHIP)', and, luciferase, assays, were, used, to, evaluate, 'TF']), verbo([binding]), complemento([and, impact, upon, 'transcription,', respectively])]). relacion([sujeto(['Active', 'FOXA1,', 'ELF1', and, 'GATA1']), verbo([binding]), complemento([sites, overlap, variable, nucleotide, positions, among, isolates, and, influenced, 'LCR', activity])]). relacion([sujeto(['Multiple', sclerosis, '(', 'MS)', is, an, 'immune-mediated', demyelinating, disease, of, the, 'CNS', that]), verbo([has]), complemento([been, linked, with, defects, in, regulatory, 'T', cell, function])]). relacion([sujeto(['Therefore,', strategies, to, selectively]), verbo([target]), complemento([pathogenic, cells, via, enhanced, regulatory, 'T', cell, activity, may, provide, therapeutic, benefit])]). relacion([sujeto([3, is, a, 'voltage-gated', potassium, channel]), verbo([expressed]), complemento([on, 'myelin-reactive', 'T', cells, from, 'MS', patients])]). relacion([sujeto([3, -, 'KO', 'Th', cells, display, suppressive, capacity]), verbo([associated]), complemento([with, increased, 'IL-10'])]). relacion([sujeto([3, -, 'KO', 'Th', cells, exhibit, a, unique, regulatory, phenotype, characterized, by, high, 'CD25,', 'CTLA4,', 'pSTAT5,', 'FoxO1,', and, 'GATA1', expression, without, a, corresponding]), verbo([increase]), complemento([in, 'Foxp3'])]). relacion([sujeto(['These', phenotypic, changes, result, from]), verbo([increased]), complemento([signaling, through, 'IL-2R'])]). relacion([sujeto([3, and]), verbo([enhances]), complemento([the, understanding, of, the, molecular, mechanism, by, which, these, cells, are, generated])]). relacion([sujeto(['This']), verbo([increased]), complemento([understanding, could, contribute, to, the, development, of, novel, therapies, for, 'MS', patients, that, promote, heightened, immune, regulation])]). relacion([sujeto(['Myeloid', malignancy, with, 'Down', syndrome, '(', 'ML-DS)', is, estimated, to]), verbo([have]), complemento([a, 'step-wise', leukemogenesis, including, 'GATA1', mutation])]). relacion([sujeto(['We']), verbo([report]), complemento([a, female, infant, with, transient, myeloproliferative, disorder, '(', 'TMD)', and, partial, trisomy, 21])]). relacion([sujeto(['With', two, other]), verbo([reported]), complemento(['TMD', cases, having, partial, trisomy, 21, ',', 'DYRK1A,', 'ERG,', and, 'ETS', were, the, most, likely, genes, involved, in, collaboration, with, the, 'GATA1', mutation])]). relacion([sujeto(['The', use, of, in, vitro, colony, assays, in, mammals]), verbo([has]), complemento([contributed, to, identification, of, erythroid, progenitor, cells, such, as, 'burst-forming', 'unit-erythroid', '(', 'BFU-E)', and, 'colony-forming', 'unit-erythroid', '(', 'CFU-E)', 'progenitors,', and, serves, to, examine, functions, of, erythropoietic, growth, factors, like, 'Erythropoietin', '(', 'Epo)', and, 'Kit', ligand])]). relacion([sujeto(['Recombinant', carp, 'Epo']), verbo([induced]), complemento([the, formation, of, 'CFU-E-like', and, 'BFU-E-like', erythroid, 'colonies,', expressing, erythroid, marker, 'genes,', 'β-globin,', epor, and, gata1])]). relacion([sujeto(['Recombinant', carp, 'Kitla', alone]), verbo([induced]), complemento([limited, colony, 'formation,', whereas, a, combination, of, 'Kitla', and, 'Epo', dramatically, enhanced, erythroid, colony, formation, and, colony, cell, 'growth,', as, well, as, stimulated, the, formation, of, 'thrombocytic/erythroid', colonies, expressing, not, only, erythroid, markers, but, also, thrombocytic, 'markers,', cd41, and, 'c-mpl'])]). relacion([sujeto(['Gene', 'synthesis,', in, 'particular,']), verbo([has]), complemento([been, considered, the, main, driver, for, the, emergence, of, this, new, scientific, discipline])]). relacion([sujeto(['Here,', we]), verbo([reveal]), complemento([an, important, 'MYBL2-VDAC2-BECN1-BCL2L1', pathway, linking, autophagy, suppression, in, the, developing, ovary])]). relacion([sujeto(['The', transcription, factors, 'GATA1', and, 'MYBL2', can]), verbo([bind]), complemento([to, and, activate, the, 'Vdac2', promoter])]). relacion([sujeto(['MYBL2']), verbo([regulates]), complemento([the, spatiotemporal, expression, of, 'VDAC2', in, the, developing, ovary])]). relacion([sujeto(['Strikingly,', in, the, 'VDAC2', transgenic, pigs, '(', 'Sus', 'scrofa/Ss),', 'VDAC2', exerts, its, function, by]), verbo([inhibiting]), complemento([autophagy, in, the, ovary])]). relacion([sujeto(['In', 'contrast,', 'Vdac2', knockout]), verbo([promotes]), complemento([autophagy])]). relacion([sujeto(['Moreover,', 'VDAC2-mediated', autophagy, suppression, is, dependent, on, its, interactions, with, both, 'BECN1', and, 'BCL2L1', to, stabilize, the, 'BECN1', and, 'BCL2L1', 'complex,']), verbo([suggesting]), complemento(['VDAC2', as, an, autophagy, suppressor, in, the, pathway])]). relacion([sujeto(['Our', findings]), verbo([provide]), complemento([a, functional, connection, among, the, 'VDAC2,', 'MYBL2,', the, 'BECN1-BCL2L1', pathway, and, autophagy, suppression, in, the, developing, 'ovary,', which, is, implicated, in, improving, female, fecundity])]). relacion([sujeto(['Insulin-like', peptide]), verbo([mediated]), complemento([body, size, plasticity, in, 'Drosophila', melanogaster, has, been, reported])]). relacion([sujeto(['Here,', our, studies, showed, that, 'IIS', pathway, and, nutrition]), verbo([regulate]), complemento([growth, and, maturation, of, the, male, accessory, gland, '(', 'MAG)', in, the, red, flour, 'beetle,', 'Tribolium', castaneum])]). relacion([sujeto(['The', size, of, 'MAG']), verbo([increased]), complemento([from, day, 1, to, day, 5, 'post-adult', emergence, '(', 'PAE)'])]). relacion([sujeto(['This']), verbo([increase]), complemento([in, the, size, of, 'MAG', is, contributed, by, an, increase, in, cell, 'size,', but, not, cell, number])]). relacion([sujeto(['The', growth, of, 'MAG', was, impaired, after, 'double-stranded', 'RNA', '(', 'dsRNA)-mediated', knockdown, in, the, expression, of, genes, coding, for, 'ILP3,', 'InR,', 'Chico,', 'PI3k,', 'AKT,', and, 'GATA1']), verbo([involved]), complemento([in, 'IIS', pathway])]). relacion([sujeto(['These', data]), verbo([suggest]), complemento([that, nutrition, signals, working, through, 'IIS', pathway, regulate, maturation, of, 'MAG', by, promoting, the, growth, of, 'MAG', cells])]). relacion([sujeto(['Defects', in, a, 'myeloid-specific', transcription, 'factor,', 'CCAAT/enhancer']), verbo([binding]), complemento(['protein-ε', '(', 'C/EBPε),', have, been, identified, in, two, cases, in, which, homozygous, frameshift, mutations, led, to, loss, of, the, leucine, zipper, domain])]). relacion([sujeto(['In', this, 'study,', we]), verbo([report]), complemento([a, 55, -, 'y-old', woman, affected, with, 'SGD', caused, by, a, novel, homozygous, 2, -, aa, deletion, '(', 'ΔRS)', in, the, leucine, zipper, domain, of, the, 'C/EBPε', gene])]). relacion([sujeto(['Biochemical', analysis, revealed, 'that,', in, contrast, to, the, two, frameshift, 'mutations,', the, 'ΔRS', mutant]), verbo([maintained]), complemento([normal, cellular, 'localization,', 'DNA-binding', 'activity,', and, 'dimerization,', and, all, three, mutants, exhibited, marked, reduction, in, transcriptional, activity])]). relacion([sujeto(['Thus,', the, 'ΔRS', likely, impairs, 'protein-protein', interaction, with, other, transcription, 'factors,', resulting, in, a]), verbo([loss]), complemento([of, transcriptional, activation])]). relacion([sujeto(['These', results, further, support, the, importance, of, the, leucine, zipper, domain, of, 'C/EBPε', for, its, essential, 'function,', and, indicate, that, multiple, molecular, mechanisms]), verbo([lead]), complemento([to, 'SGD'])]). relacion([sujeto(['Using', gene, disruption, models, of, 'Gata1', and, 'Nfe2,', we, demonstrate, that, perturbing, essential, adult, 'MK', genes]), verbo([causes]), complemento([an, analogous, phenotype, in, the, early, embryo, before, the, onset, of, hematopoietic, 'stem/progenitor', 'cell-driven', '(', 'definitive)', hematopoiesis])]). relacion([sujeto(['Finally,', we, present, the, surprising]), verbo([finding]), complemento([that, 'DPFC', and, 'MK', commitment, from, their, respective, precursors, is, 'MPL', independent, in, vivo, but, that, completion, of, 'MK', differentiation, and, establishment, of, the, prenatal, platelet, mass, is, dependent, on, 'MPL', expression])]). relacion([sujeto(['Non-HIV-infected', individuals, taking, immunosuppressive, drug, regimens]), verbo([targeting]), complemento(['T', cell, activation, are, also, susceptible])]). relacion([sujeto(['In', 'wild-type', 'mice,', a, strong, eosinophil, signature, was, observed, at, day, 14, post, 'Pneumocystis', 'challenge,', and, eosinophils, were]), verbo([increased]), complemento([in, the, bronchoalveolar, lavage, fluid, of, 'wild-type', mice])]). relacion([sujeto(['To', drive, eosinophilia, in, 'vivo,', 'Rag1(-/-)', mice, were, treated, with, a, plasmid]), verbo([expressing]), complemento(['IL-5', '(', 'pIL5)', or, an, empty, plasmid, control, via, hydrodynamic, injection])]). relacion([sujeto(['The', 'pIL5-treated', mice, had]), verbo([increased]), complemento([serum, 'IL-5', and, eosinophilia, in, the, 'lung,', as, well, as, reduced, 'Pneumocystis', 'burden,', compared, with, mice, treated, with, control, plasmid])]). relacion([sujeto(['In', 'addition,', pIL5, treatment, could]), verbo([induce]), complemento([eosinophilia, and, reduce, 'Pneumocystis', burden, in, 'CD4-depleted', 'C57BL/6', and, 'BALB/c', 'mice,', but, not, 'eosinophilopoiesis-deficient', 'Gata1(tm6Sho)/J', mice])]). relacion([sujeto(['Taken', 'together,', these, results, demonstrate, that, an, early, role, of, 'CD4(+)', 'T', cells, is, to]), verbo([recruit]), complemento([eosinophils, to, the, lung, and, that, eosinophils, are, a, novel, candidate, for, future, therapeutic, development, in, the, treatment, of, 'Pneumocystis', pneumonia, in, the, immunosuppressed, population])]). relacion([sujeto(['Regulated', gene, expression, controls, organismal, 'development,', and, variation, in, regulatory, patterns]), verbo([has]), complemento([been, implicated, in, complex, traits])]). relacion([sujeto(['The', level, of]), verbo([binding]), complemento([signal, for, 'TAL1', or, 'GATA1', did, not, help, distinguish, 'TAL1-bound', 'DNA', segments, as, active, versus, inactive, 'enhancers,', nor, did, the, density, of, 'regulation-related', histone, modifications])]). relacion([sujeto(['A', 'meta-analysis', of, results, from, this, and, other, studies, '(', 273, tested, predicted, 'enhancers)', showed, that, the, presence, of, 'TAL1,', 'GATA1,', 'EP300,', 'SMAD1,', 'H3K4', 'methylation,', 'H3K27ac,', and, 'CAGE', tags, at, 'DNase', hypersensitive, sites, gave, the, most, accurate, predictors, of, enhancer, 'activity,', with, a, success, rate, over, 80, '%', and, a, median, threefold]), verbo([increase]), complemento([in, activity])]). relacion([sujeto(['Chromatin', accessibility, assays, and, the, histone, modifications, 'H3K4me1', and, 'H3K27ac', were, sensitive, for]), verbo([finding]), complemento(['enhancers,', but, they, have, high, false, positive, rates, unless, transcription, factor, occupancy, is, also, included])]). relacion([sujeto(['Trisomy', of, the, 'Erg', gene, is]), verbo([required]), complemento([for, myeloproliferation, in, the, 'Ts(1716)65Dn', 'DS', mouse, model])]). relacion([sujeto(['We', demonstrate, here, that, genetic, changes, specifically, attributable, to, trisomy, of, 'Erg']), verbo([lead]), complemento([to, lineage, priming, of, primitive, and, early, multipotential, progenitor, cells, in, 'Ts(1716)65Dn', 'mice,', excess, 'megakaryocyte-erythroid', 'progenitors,', and, malignant, myeloproliferation])]). relacion([sujeto(['Gene', expression, changes, dependent, on, trisomy, of, 'Erg', in, 'Ts(1716)65Dn', multilineage, progenitor, cells, were, correlated, with, those]), verbo([associated]), complemento([with, trisomy, of, 'HSA21', in, human, 'DS', hematopoietic, stem, and, primitive, progenitor, cells])]). relacion([sujeto(['These', data]), verbo([suggest]), complemento([a, role, for, 'ERG', as, a, regulator, of, hematopoietic, lineage, 'potential,', and, that, trisomy, of, 'ERG', in, the, context, of, 'DS', foetal, liver, hemopoiesis, drives, the, 'pre-leukemic', changes, that, predispose, to, subsequent, 'DS-TMD', and, 'DS-AMKL'])]). relacion([sujeto(['The', reproductive, homeobox, 'X-linked,', 'Rhox,', genes, encode, transcription, factors, that, are, selectively]), verbo([expressed]), complemento([in, reproductive, tissues])]). relacion([sujeto(['While', there, are, 33, 'Rhox', genes, in, 'mice,', only, 'Rhox', and, 'Rhox8', are]), verbo([expressed]), complemento([in, 'Sertoli', 'cells,', suggesting, that, they, may, regulate, the, expression, of, 'somatic-cell', gene, products, crucial, for, germ, cell, development])]). relacion([sujeto(['However,', other, 'Sertoli', 'markers,', 'Gata1', and, 'Rhox5,']), verbo([maintained]), complemento([normal, expression, 'patterns,', suggesting, that, the, knockdown, was, specific])]). relacion([sujeto(['Interestingly,', male, 'RHOX8-knockdown', animals, showed, significantly, reduced, spermatogenic, 'output,']), verbo([increased]), complemento([germ, cell, 'apoptosis,', and, compromised, sperm, 'motility,', leading, to, impaired, fertility])]). relacion([sujeto(['This']), verbo([suggests]), complemento([that, while, reduction, in, levels, of, 'RHOX5', and, 'RHOX8', in, 'Sertoli', cells, elicits, similar, 'phenotypes,', these, genes, are, not, entirely, redundant])]). relacion([sujeto(['Taken', 'together,', our, study, underscores, the, importance, of, 'Rhox', genes, in, male, fertility, and]), verbo([suggests]), complemento([that, 'Sertoli', 'cell-specific', expression, of, 'Rhox5', and, 'Rhox8', is, critical, for, complete, male, fertility])]). relacion([sujeto(['Embryonic', stem, '(', 'ES)', and]), verbo([induced]), complemento([pluripotent, stem, '(', 'iPS)', cells, represent, a, potential, source, of, megakaryocytes, and, platelets, for, transfusion, 'therapies;', 'however,', the, majority, of, current, 'ES/iPS', cell, differentiation, protocols, are, limited, by, low, yields, of, hematopoietic, progeny])]). relacion([sujeto(['In', both, mice, and, 'humans,', mutations, in, the, 'gene-encoding', transcription, factor, 'GATA1']), verbo([cause]), complemento([an, accumulation, of, 'proliferating,', developmentally, arrested, 'megakaryocytes,', suggesting, that, 'GATA1', suppression, in, 'ES', and, iPS, 'cell-derived', hematopoietic, progenitors, may, enhance, megakaryocyte, production])]). relacion([sujeto(['Here,', we, engineered, 'ES', cells, from, 'WT', mice, to]), verbo([express]), complemento([a, 'doxycycline-regulated', '(', 'dox-regulated)', shRNA, that, targets, 'Gata1', transcripts, for, degradation])]). relacion([sujeto(['Our', findings]), verbo([provide]), complemento([a, readily, reproducible, strategy, to, exponentially, expand, 'ES', 'cell-derived', 'megakaryocyte-erythroid', progenitors, that, have, the, capacity, to, differentiate, into, functional, 'platelet-producing', megakaryocytes])]). relacion([sujeto(['The', creation, of, a, 'donor-independent', source, of, platelets]), verbo([has]), complemento([been, 'challenging;', 'however,', recent, advances, show, growing, promise, for, alternative, platelet, sources])]). relacion([sujeto(['Pluripotent', stem, cells]), verbo([have]), complemento([the, capacity, to, differentiate, into, mature, megakaryocytes, with, the, ability, to, produce, functional, platelets])]). relacion([sujeto(['In', 'vertebrates,', heart, pumping, is]), verbo([required]), complemento([for, cardiac, morphogenesis, and, altering, myocardial, contractility, leads, to, abnormal, intracardiac, flow, forces, and, valve, defects])]). relacion([sujeto(['Among', the, different, mechanical, cues, generated, in, the, developing, 'heart,', oscillatory, flow]), verbo([has]), complemento([been, proposed, to, be, an, essential, factor, in, instructing, endocardial, cell, fate, toward, valvulogenesis, and, leads, to, the, expression, of, 'klf2a,', a, known, atheroprotective, transcription, factor])]). relacion([sujeto(['Here,', we, establish, that, mechanosensitive, channels, are]), verbo([activated]), complemento([in, response, to, oscillatory, flow, and, directly, affect, valvulogenesis, by, modulating, the, endocardial, cell, response])]). relacion([sujeto(['Furthermore,', we, show, that, an, endocardial, calcium, response, and, the, 'flow-responsive', klf2a, promoter, are]), verbo([modulated]), complemento([by, the, oscillatory, flow, through, 'Trpv4,', a, mechanosensitive, ion, channel, specifically, expressed, in, the, endocardium, during, heart, valve, development])]). relacion([sujeto(['We', made, similar, observations, for, 'Trpp2,', a, known, 'Trpv4', 'partner,', and, show, that, both, the, absence, of, 'Trpv4', or, 'Trpp2']), verbo([leads]), complemento([to, valve, defects])]). relacion([sujeto(['This', work, identifies, a, major, mechanotransduction, pathway]), verbo([involved]), complemento([during, valve, formation, in, vertebrates])]). relacion([sujeto(['The', 'PPP2R5C-siRNA799', was, transduced, into, 'Jurkat', cells, by, 'nucleofection,', the, total, 'RNA', was, isolated, from, treated, 'Jurkat', cells, after, culture, for, 48, 'hours;', the]), verbo([target]), complemento([sequences, were, prepared, by, revevse, transcription, after, mRNA, 'purification,', and, were, hybridized, with, affymetrix, gene, expression, profile, chip, 3, '\'', 'IVT'])]). relacion([sujeto(['The', 'down-regulation', of, 'PPP2R5C', gene, expression, in, 'Jurkat', cells, via, 'RNA', interference, to, a, certain, degree, can]), verbo([inhibit]), complemento(['TAL1', signaling, pathway, 'genes,', thereby, suppresses, the, proliferation, of, 'Jurkat', cells])]). relacion([sujeto(['Diamond', 'Blackfan', anemia, '(', 'DBA)', is, a, genetically, and, clinically, heterogeneous, ribosomopathy, and, inherited, bone, marrow, failure, syndrome, characterized, by, 'anemia,', 'reticulocytopenia,', and]), verbo([decreased]), complemento([erythroid, precursors, in, the, bone, marrow, with, an, increased, risk, of, malignancy, 'and,', in, approximately, 50, '%', ',', physical, abnormalities])]). relacion([sujeto(['Most']), verbo([responded]), complemento([initially, to, 'steroids,', while, 5, responses, were, transient])]). relacion([sujeto(['Mutations', in, 'RP', genes, were, detected, in, 35, of, 57, patients, 'studied:', 15, in, 'RPS19,', 6, in, 'RPL5,', 3, in, 'RPS7,', 3, each, in, 'RPS10,', 'RPS26,', and, 'RPL11', and, 1, each, in, 'RPS24', and, 'RPL35a;', 24, of, these, mutations]), verbo([have]), complemento([not, been, previously, reported])]). relacion([sujeto(['One', patient, had, a, balanced, chromosomal, translocation]), verbo([involving]), complemento(['RPS19'])]). relacion([sujeto(['In', our, cohort, from, an, ethnically, diverse, population, the, distribution, of, mutations, among, 'RP', genes, was, approximately, the, same, as, was]), verbo([reported]), complemento([by, 'others,', although, within, genotypes, most, of, the, mutations, had, not, been, previously, reported])]). relacion([sujeto(['Here,', we]), verbo([report]), complemento([the, outcome, of, 97, pediatric, patients, with, de, novo, 'AMKL', '(', excluding, 'Down', syndrome, '[', 'DS])', enrolled, in, the, prospective, multicenter, studies, 'AML-BFM', 98, and, 'AML-BFM', 4, '(', 1998, -, 2014, ')'])]). relacion([sujeto(['Allogeneic', hematopoietic, stem, cell, transplantation, in, first, remission, did, not]), verbo([provide]), complemento([a, significant, survival, benefit, '(', 5, -, year, 'OS', 70, ±, 11, '%', vs])]). relacion([sujeto(['AMKL', patients, with]), verbo([gain]), complemento([of, chromosome, 21, had, a, superior, 5, -, year, 'OS', '(', 80, ±, 9, '%', ',', 'P', log, rank, =, 0.034, ')', ',', whereas, translocation, 't(1;22)(p13;q13)', was, associated, with, an, inferior, 5, -, year, 'event-free', survival, '(', 38, ±, 17, '%', ',', 'P', log, rank, =, 0.04, ')'])]). relacion([sujeto(['Nevertheless,', with, intensive, therapy, 'regimens,', a, steep]), verbo([increase]), complemento([in, the, survival, rates, was, achieved])]). relacion([sujeto(['However,', concerns]), verbo([have]), complemento([been, raised, regarding, the, potential, deleterious, role, of, high, vitamin, 'D', levels, in, the, development, of, esophageal, adenocarcinoma, '(', 'EAC)'])]). relacion([sujeto(['It', was]), verbo([associated]), complemento([with, an, approximately, 'two-fold', reduced, risk, of, 'RE,', 'BE', and, 'EAC'])]). relacion([sujeto(['The', rs1989969T, allele]), verbo([causes]), complemento([a, 'GATA-1', transcription, factor, binding, site, to, appear])]). relacion([sujeto(['The', rs2238135G, allele, was]), verbo([associated]), complemento([with, a, significantly, reduced, 'VDR', expression, in, 'BE;', for, the, rs1989969T, 'allele,', a, trend, in, reduced, 'VDR', expression, was, observed])]). relacion([sujeto(['We', identified, a, 'VDR', haplotype]), verbo([associated]), complemento([with, reduced, esophageal, 'VDR', expression, and, a, reduced, incidence, of, 'RE,', 'BE', and, 'EAC'])]). relacion([sujeto(['Morphologic', analysis]), verbo([suggested]), complemento([erythropoietic, activity, in, fetal, 'spleen,', but, it, remained, unclear, how, erythropoiesis, was, regulated])]). relacion([sujeto(['To', address, this, 'question,', we, performed, flow, cytometric, analysis, and, observed, that, the, number, of, spleen, erythroid, cells]), verbo([increased]), complemento([18.6, -, fold, from, 16.5, to, 19.5, days, 'post-coitum', '(', 'dpc)'])]). relacion([sujeto(['Among', erythropoietic, 'cytokines,', 'SCF', and, 'IGF-1', were, primarily]), verbo([expressed]), complemento([in, 'hematopoietic,', endothelial, and, 'mesenchymal-like', fetal, spleen, cells])]). relacion([sujeto(['Cultures', treated, with, 'SCF', 'and/or', 'IGF-1R', inhibitors, showed, significantly]), verbo([decreased]), complemento(['CD45-c-Kit-CD71+/-Ter119+', erythroid, cells, and, downregulated, 'Gata1,', 'Klf1', and, 'β-major', globin, expression])]). relacion([sujeto(['Administration', of, these, inhibitors, to, pregnant, mice, significantly]), verbo([decreased]), complemento([the, number, of, 'CD45-c-Kit-CD71+/-Ter119+', cells, and, downregulated, 'β-major', globin, gene, expression, in, embryos, derived, from, these, mice])]). relacion([sujeto(['TFIID,', comprised, of, the, 'TATA']), verbo([binding]), complemento([protein, '(', 'TBP)', and, 13, 'TBP-associated', factors, '(', 'TAFs),', is, the, 'GTF', that, is, thought, to, recognize, the, promoter, sequences, allowing, 'site-specific', 'PIC', assembly])]). relacion([sujeto(['Transcriptional', 'cofactors,', such, as, 'SAGA,', are, also, necessary, for, tightly]), verbo([regulated]), complemento([transcription, initiation])]). relacion([sujeto(['By', ablating, 'TAF10', specifically, in, erythroid, cells, in, 'vivo,', we, observed, a, differentiation, block, accompanied, by, deregulated, 'GATA1']), verbo([target]), complemento(['genes,', including, 'Gata1', 'itself,', suggesting, functional, cross, talk, between, 'GATA1', and, 'TAF10'])]). relacion([sujeto(['Additionally,', we, analyzed, by, mass, spectrometry, the, composition, of, 'TFIID', and, 'SAGA', complexes, in, mouse, and, human, cells, and]), verbo([found]), complemento([that, their, global, integrity, is, 'maintained,', with, minor, 'changes,', during, erythroid, cell, differentiation, and, development])]). relacion([sujeto(['In', agreement, with, our, functional, 'data,', we, show, that, 'TAF10']), verbo([interacts]), complemento([directly, with, 'GATA1', and, that, 'TAF10', is, enriched, on, the, 'GATA1', locus, in, human, fetal, erythroid, cells])]). relacion([sujeto(['The', erythropoietin, '(', 'Epo)', receptor, '(', 'EpoR)', is]), verbo([expressed]), complemento([in, the, brain, and, was, shown, to, have, neuroprotective, effects, against, brain, damage, in, animal, models])]). relacion([sujeto(['Thus,', we, propose, that, 'Klotho', can]), verbo([stimulate]), complemento([the, expression, of, 'EpoR', in, neuronal, cells, to, enhance, 'Epo-mediated', protection])]). relacion([sujeto(['In', 'H19-7', 'cells,', 'Klotho']), verbo([increased]), complemento([the, expression, of, both, the, 'EpoR', protein, and, mRNA])]). relacion([sujeto(['Klotho', also]), verbo([enhanced]), complemento([the, transcription, activity, of, the, 'EpoR', promoter, in, 'H19-7', cells])]). relacion([sujeto(['Finally,', the, silencing, of, 'GATA1', diminished, the, 'Klotho-induced']), verbo([increase]), complemento([in, 'EpoR', protein, and, mRNA, expression, as, well, as, its, promoter, activity])]). relacion([sujeto(['In', 'conclusion,', 'Klotho']), verbo([increased]), complemento(['EpoR', expression, in, neuronal, cells, through, 'GATA1,', thereby, enabling, 'EpoR', to, function, as, a, cytoprotective, protein, against, oxidative, injury])]). relacion([sujeto([1, ',']), verbo([inhibit]), complemento([each, other, but, activate, themselves, so, as, to, regulate, the, choice, between, alternative, cell, fates, have, been, extensively, studied])]). relacion([sujeto(['Here', we, take, a, general, modeling, and, analyzing, approach, and, show, that, the, lateral, inhibition, with, symmetry, and, asymmetry, can]), verbo([lead]), complemento([to, different, bifurcation, dynamics])]). relacion([sujeto(['Our', previous, study, on, the, dynamic, transcriptomes]), verbo([activated]), complemento([during, human, erythropoiesis, suggested, that, transcription, factor, forkhead, box, 'O3', '(', 'FOXO3)', possibly, plays, a, role, in, erythroid, differentiation])]). relacion([sujeto(['Functional', studies, in, human, cell, line, 'TF-1', indicated, that, 'FOXO3', knockdown, repressed, erythropoietin, '(', 'EPO)-induced', erythroid, differentiation, by]), verbo([activating]), complemento([promoter, region, of, 'B-cell', translocation, gene, 1, '(', 'BTG1),', thereby, regulating, its, expression])]). relacion([sujeto(['Further', study]), verbo([suggested]), complemento([that, 'BTG1', is, partially, responsible, for, 'FOXO3', regulation, in, erythroid, differentiation, of, 'TF-1', cells, but, is, inconsequential, in, zebrafish])]). relacion([sujeto(['Taken', 'together,', we]), verbo([found]), complemento([that, 'FOXO3', plays, an, important, role, in, erythroid, differentiation, in, both, human, 'TF-1', cells, and, 'zebrafish,', but, the, mechanism, underlying, this, regulation, still, remains, unclear])]). relacion([sujeto(['Erythropoietin', '(', 'Epo)', and, its, receptor, '(', 'EpoR)', are]), verbo([required]), complemento([for, the, regulation, of, erythropoiesis])]). relacion([sujeto(['Epo']), verbo([binds]), complemento([to, the, 'EpoR', homodimer, on, the, surface, of, erythroid, progenitors, and, 'erythroblasts,', and, positions, the, intracellular, domains, of, the, homodimer, to, be, in, close, proximity, with, each, other])]). relacion([sujeto(['Here,', we, established, a, system, of, chemically]), verbo([regulated]), complemento([erythropoiesis, in, transgenic, mice, expressing, a, modified, 'EpoR', intracellular, domain, '(', amino, acids, 247, -, 406, ')', in, which, dimerization, is, induced, using, a, specific, compound, '(', chemical, inducer, of, 'dimerization,', 'CID)'])]). relacion([sujeto(['Erythropoiesis', is, reversibly]), verbo([induced]), complemento([by, oral, administration, of, the, 'CID', to, the, transgenic, mice])]). relacion([sujeto(['Cell', differentiation, was]), verbo([induced]), complemento([by, hemin, and, the, effect, of, 'pre-incubation', with, 'T3', '(', 0.1, to, 100, 'nM)', was, analyzed, by, measuring, the, 'benzidine-positive', 'rate,', hemoglobin, 'content,', 'CD71', expression, '(', transferrin, 'receptor),', and, mRNA, expression, for, transcription, factors, related, to, erythropoiesis, and, thyroid, hormone, receptors, '(', 'TRs)'])]). relacion([sujeto(['Hemin,', a, promoter, of, erythroid, 'differentiation,']), verbo([increased]), complemento([the, levels, of, mRNAs, for, 'TRα,', 'TRβ,', and, retinoid, 'X', receptor, α, '(', 'RXRα),', as, well, as, those, for, nuclear, 'factor-erythroid', 2, '(', 'NFE2),', 'GATA-binding', protein, 1, '(', 'GATA1)', and, 'GATA-binding', protein, 2, '(', 'GATA2)'])]). relacion([sujeto(['T3', at, 100, nM, did, not, affect, cell, viability, and, 'proliferation,']), verbo([suggesting]), complemento([that, the, abrogation, of, erythropoiesis, enhancement, was, not, due, to, toxicity])]). relacion([sujeto(['T3', at, 100, nM, also, significantly]), verbo([inhibited]), complemento([expression, of, 'GATA2', and, 'RXRα', 'mRNA,', compared, to, 1, nM, 'T3'])]). relacion([sujeto(['Cyclosporin', 'A', '(', 'CSA)']), verbo([suppresses]), complemento([immune, function, by, blocking, the, cyclophilin, 'A', and, 'calcineurin/NFAT', signaling, pathways])]). relacion([sujeto(['In', addition, to, 'immunosuppression,', 'CSA']), verbo([has]), complemento([also, been, shown, to, have, a, wide, range, of, effects, in, the, cardiovascular, system, including, disruption, of, heart, valve, 'development,', smooth, muscle, cell, 'proliferation,', and, angiogenesis, inhibition])]). relacion([sujeto(['Circumstantial', evidence]), verbo([has]), complemento([suggested, that, 'CSA', might, control, 'Notch', signaling, which, is, also, a, potent, regulator, of, cardiovascular, function])]). relacion([sujeto(['We']), verbo([found]), complemento([that, 'CSA', blocked, 'JAG1,', but, not, 'Dll4', mediated, 'Notch1', 'NICD', cleavage, in, transfected, 293, 'T', cells, and, decreased, 'Notch', signaling, in, zebrafish, embryos])]). relacion([sujeto(['CSA', suppression, of, 'Notch', was, linked, to, cyclophilin, 'A', but, not, 'calcineurin/NFAT', inhibition, since, 'N-MeVal-4-CsA', but, not, 'FK506']), verbo([decreased]), complemento(['Notch1', 'NICD', cleavage])]). relacion([sujeto(['Most', 'strikingly,', 'CSA', treated, embryos, exhibited, a, progressive, decline, in, blood, flow, that, was]), verbo([associated]), complemento([with, eventual, collapse, of, vascular, luminal, structures])]). relacion([sujeto(['Vascular', collapse, in, zebrafish, embryos, was, partially, rescued, by, global, 'Notch', inhibition, with, 'DAPT']), verbo([suggesting]), complemento([that, disruption, of, normal, 'Notch', signaling, by, 'CSA', may, be, linked, to, vascular, collapse])]). relacion([sujeto(['However,', multiple, signaling, pathways, likely]), verbo([cause]), complemento([the, vascular, collapse, phenotype, since, both, cyclophilin, 'A', and, 'calcineurin/NFAT', were, required, for, normal, vascular, function])]). relacion([sujeto(['GATA', transcription, factors, are, evolutionarily]), verbo([conserved]), complemento([transcriptional, regulators, that, recognize, promoter, elements, with, a, 'G-A-T-A', core, sequence])]). relacion([sujeto(['We', also, review, 'GATA23,', a, regulator, of, lateral, root, initiation, from, 'Arabidopsis', that, is, closely, related, to, 'GNC', and, 'GNL', but]), verbo([has]), complemento([a, degenerate, 'LLM-domain', that, is, seemingly, specific, for, the, 'Brassicaceae', family])]). relacion([sujeto(['The', 'Brassicaceae-specific', 'GATA23', and, the, 'monocot-specific', 'HAN-domain', 'GATAs']), verbo([provide]), complemento([evidence, that, neofunctionalization, of, 'B-GATAs', was, used, during, plant, evolution, to, expand, the, functional, repertoire, of, these, transcription, factors])]). relacion([sujeto(['We', then, applied, these, definitions, to, 'DBA', and, identified, 'that,', compared, with, 'controls,', 'frequency,', and, clonogenicity, of, 'DBA,', 'EEP', and, 'LEP', are, significantly]), verbo([decreased]), complemento([in, 'transfusion-dependent', but, restored, in, 'corticosteroid-responsive', patients])]). relacion([sujeto(['GATA1', gene, expression, is, strictly]), verbo([regulated]), complemento([at, the, transcriptional, level])]). relacion([sujeto(['While', the, regulatory, mechanisms, governing, mouse, 'Gata1', '(', 'mGata1)', gene, expression]), verbo([have]), complemento([been, studied, 'extensively,', how, expression, of, the, human, 'GATA1', '(', 'hGATA1)', gene, is, regulated, remains, to, be, elucidated])]). relacion([sujeto(['We']), verbo([found]), complemento([a, novel, insulator, element, at, 29, kb, 5, '\'', to, the, hGATA1, gene, and, refer, to, this, element, as, the, 5, '\'', 'CCCTC-binding', factor, '(', 'CTCF)', site])]). relacion([sujeto(['Substitution', mutation, of, the, 5, '\'', 'CTCF', site, in, the, hGATA1, 'BAC', disrupted, the, chromatin, architecture, and]), verbo([led]), complemento([to, a, reduction, of, hGATA1, expression, in, splenic, erythroblasts, under, conditions, of, stress, erythropoiesis])]). relacion([sujeto(['Our', results, demonstrate, that, expression, of, the, hGATA1, gene, is]), verbo([regulated]), complemento([through, the, chromatin, architecture, organized, by, 5, '\'', 'CTCF', 'site-mediated', intrachromosomal, interactions, in, the, hGATA1, locus])]). relacion([sujeto(['CRISPR/Cas9', technology, of, genome, editing]), verbo([has]), complemento([greatly, facilitated, the, targeted, inactivation, of, genes, in, vitro, and, in, vivo, in, a, wide, range, of, organisms])]). relacion([sujeto(['Here,', we]), verbo([report]), complemento([a, simple, and, scalable, 'CRISPR-based', vector, system, for, 'tissue-specific', gene, inactivation, in, zebrafish])]). relacion([sujeto(['Urod']), verbo([targeting]), complemento([yielded, red, fluorescent, erythrocytes, in, zebrafish, 'embryos,', recapitulating, the, phenotype, observed, in, the, yquem, mutant])]). relacion([sujeto(['Celiac', disease, '(', 'CD)', is, an, autoimmune, disease]), verbo([induced]), complemento([by, an, autoimmune, reaction, to, indigested, 'gluten,', which, occurs, in, genetically, predisposed, population])]). relacion([sujeto(['The', etiology, of, 'CD', is, linked, to, innate, and, adaptive, 'immunity,', mostly]), verbo([mediated]), complemento([by, 'lymphocytes,', especially, 'T', 'cells,', infiltrating, into, the, small, intestinal, wall])]). relacion([sujeto(['The', plethora, of, 'T', cell, subtypes]), verbo([activated]), complemento([in, 'CD', leads, to, simultaneous, activation, of, different, signaling, cascades, including, 'GATA1,', 'NF-kB,', 'JAK', or, 'STAT5', the, activity, of, which, may, be, modified, by, diet, or, drugs])]). relacion([sujeto(['This', 'mini-review', will, summarize, the, current, knowledge, on, the, role, of, 'CD4+', 'T', cell, and, 'CD8+', 'T', cell, in, clinical, and, experimental, 'CD', and, will, describe, how, 'T', 'cell-activated', signaling, pathways, and, locally]), verbo([released]), complemento([proteins, may, be, influenced, by, dietary, factors, and, drugs, used, in, 'CD', treatment])]). relacion([sujeto(['These', changes, are]), verbo([caused]), complemento([by, equally, dramatic, alterations, in, gene, 'expression,', which, in, turn, are, driven, by, changes, in, the, abundance, and, binding, patterns, of, transcription, factors, such, as, 'GATA1'])]). relacion([sujeto(['We']), verbo([have]), complemento([studied, the, dynamics, of, 'GATA1', binding, by, 'ChIP-seq', and, the, global, expression, responses, by, 'RNA-seq', in, a, 'GATA1-dependent', mouse, cell, line, model, for, erythroid, 'maturation,', in, both, cases, examining, seven, progressive, stages, during, differentiation])]). relacion([sujeto(['Analyses', of, these, data, should]), verbo([provide]), complemento([insights, both, into, mechanisms, of, regulation, '(', early, versus, late, 'targets)', and, the, consequences, in, cell, physiology, '(', e])]). relacion([sujeto([distinctive, categories, of, genes]), verbo([regulated]), complemento([at, progressive, stages, of, 'differentiation)'])]). relacion([sujeto(['Epithelial-mesenchymal', transition, '(', 'EMT)', is, a, key, process, in, tumor, metastatic, cascade, that, is, characterized, by, the]), verbo([loss]), complemento([of, 'cell-cell', 'junctions,', resulting, in, the, acquisition, of, migratory, and, invasive, properties])]). relacion([sujeto(['E-cadherin', is, a, major, component, of, intercellular, junctions, and, the, reduction, or]), verbo([loss]), complemento([of, its, expression, is, a, hallmark, of, 'EMT'])]). relacion([sujeto(['Transcription', factor, 'GATA1']), verbo([has]), complemento([a, critical, 'anti-apoptotic', role, in, breast, 'cancer,', but, its, function, for, metastasis, has, not, been, investigated])]). relacion([sujeto(['Here,', we]), verbo([found]), complemento([that, 'GATA1,', as, a, novel, 'E-cadherin', 'repressor,', promotes, 'EMT', in, breast, cancer, cells])]). relacion([sujeto(['GATA1']), verbo([binds]), complemento([to, 'E-cadherin', 'promoter,', 'down-regulates', 'E-cadherin', 'expression,', disrupts, intercellular, junction, and, promotes, metastasis, of, breast, cancer, cell, in, vivo])]). relacion([sujeto(['Moreover,', 'GATA1', is, a, new, substrate, of, 'p21-activated', kinase, 5, '(', 'PAK5),', which, is]), verbo([phosphorylated]), complemento([on, serine, 161, and, 187, '(', 'S161', and, 'S187)'])]). relacion([sujeto(['GATA1']), verbo([recruits]), complemento(['HDAC3/4', to, 'E-cadherin', 'promoter,', which, is, reduced, by, 'GATA1', 'S161A', 'S187A', mutant])]). relacion([sujeto(['These', data, indicate, that]), verbo([phosphorylated]), complemento(['GATA1', recruits, more, 'HDAC3/4', to, promote, transcriptional, repression, of, 'E-cadherin,', leading, to, the, 'EMT', of, breast, cancer, cells])]). relacion([sujeto(['Our', findings]), verbo([provide]), complemento([insights, into, the, novel, function, of, 'GATA1,', contributing, to, a, better, understanding, of, the, 'EMT,', indicating, that, 'GATA1', and, its, phosphorylation, may, play, an, important, role, in, the, metastasis, of, breast, cancer])]). relacion([sujeto(['The', 'NFE2', protein, forms, heterodimers, with, small, 'MAF', 'proteins,', and, the, resulting, complex]), verbo([binds]), complemento([to, regulatory, elements, in, a, large, number, of, target, genes])]). relacion([sujeto(['In', contrast, to, other, 'CNC', transcription, family, members, including, 'NFE2L1', '(', 'NRF1),', 'NFE2L2', '(', 'NRF2)', and, 'NFE2L3', '(', 'NRF3),', which, are, widely, 'expressed,', earlier, studies, had]), verbo([suggested]), complemento([that, the, major, sites, of, 'NFE2', expression, are, hematopoietic, cells])]). relacion([sujeto(['Based', on, cell, culture, studies, it, was, proposed, that, this, protein]), verbo([acts]), complemento([as, a, critical, regulator, of, globin, gene, expression])]). relacion([sujeto(['Indeed,', absence, of, 'NFE2']), verbo([led]), complemento([to, severely, impaired, platelet, production])]). relacion([sujeto(['Surprisingly,', it, was, recently]), verbo([found]), complemento([that, 'NFE2', also, has, a, role, in, 'non-hematopoietic', 'tissues,', such, as, the, 'trophoblast,', in, which, it, is, also, 'expressed,', as, well, as, the, 'bone,', opening, the, door, to, new, research, areas, for, this, transcription, factor])]). relacion([sujeto(['Important', strides]), verbo([have]), complemento([been, made, with, respect, to, the, clinical, significance, of, 'NFE2,', linking, this, transcription, factor, to, hematological, disorders, such, as, polycythemias])]). relacion([sujeto(['We', encountered, a, case, of, neonatal, acute, megakaryoblastic, leukemia, not]), verbo([associated]), complemento([with, 'Down', syndrome, '(', 'DS)'])]). relacion([sujeto(['Molecular', cytogenetic, analysis, of, leukemic, blast, cells, indicated, that]), verbo([increased]), complemento([blast, cell, status, was, caused, by, transient, abnormal, myelopoiesis, with, trisomy, 21, and, 'GATA1', mutation])]). relacion([sujeto(['We', used, genomic, and, genetic, approaches, to, examine, 'BET', function, in, a, hematopoietic, maturation, system, driven, by, 'GATA1,', an, acetylated, transcription, factor, previously, shown, to]), verbo([interact]), complemento([with, 'BETs'])]). relacion([sujeto(['We']), verbo([found]), complemento([that, 'BRD2,', 'BRD3,', and, 'BRD4', were, variably, recruited, to, 'GATA1-regulated', 'genes,', with, 'BRD3', binding, the, greatest, number, of, 'GATA1-occupied', sites])]). relacion([sujeto(['Mechanistically,', 'BETs']), verbo([promoted]), complemento([chromatin, occupancy, of, 'GATA1', and, subsequently, supported, transcriptional, activation])]). relacion([sujeto(['Consistent', with, functional, overlap, among, 'BET', 'proteins,', forced, 'BRD3', expression, substantially, rescued, defects]), verbo([caused]), complemento([by, 'BRD2', deficiency])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, pharmacologic, 'BET', inhibition, should, be, interpreted, in, the, context, of, distinct, steps, in, transcriptional, activation, and, overlapping, functions, among, 'BET', family, members])]). relacion([sujeto(['Autophagy', is, a, process, that]), verbo([leads]), complemento([to, the, degradation, of, unnecessary, or, dysfunctional, cellular, components, and, 'long-lived', protein, aggregates])]). relacion([sujeto(['Here,', the, modulators, of, autophagy, that]), verbo([regulate]), complemento([erythroid, differentiation, were, 'summarized,', including, 'autophagy-related', '(', 'Atg)', 'genes,', the, 'B-cell', lymphoma, 2, '(', 'Bcl-2)', family, member, 'Bcl-2/adenovirus', 'E1B', 19, kDa, interacting, protein, 3, -, like, '(', 'Nix/Binp3L),', transcription, factors, globin, transcription, factor, 1, '(', 'GATA1)', and, forkhead, box, 'O3', '(', 'FoxO3),', intermediary, factor, 'KRAB-associated', protein1, '(', 'KAP1),', and, other, 'modulators,', such, as, focal, adhesion, kinase, 'family-interacting', protein, of, 200, -, kDa, '(', 'FIP200),', 'Ca2+', and, 15, -, lipoxygenase])]). relacion([sujeto(['Germ-line', mutations, that]), verbo([cause]), complemento([loss, of, full, length, 'GATA1,', but, allow, for, expression, of, the, short, isoform, '(', 'GATA1s),', are, associated, with, defective, erythropoiesis, in, a, subset, of, patients, with, 'Diamond', 'Blackfan', 'Anemia'])]). relacion([sujeto(['We', discovered, that, compared, to, 'GATA1,', 'GATA1s', is, less, able, to]), verbo([activate]), complemento([the, erythroid, gene, expression, program, and, terminal, differentiation, in, cells, with, dual, 'erythroid-megakaryocytic', differentiation, potential])]). relacion([sujeto(['Moreover,', we]), verbo([found]), complemento([that, 'GATA1s', bound, to, many, of, its, 'erythroid-specific', target, genes, less, efficiently, than, full, length, 'GATA1'])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, the, impaired, ability, of, 'GATA1s', to, promote, erythropoiesis, in, 'DBA', may, be, caused, by, failure, to, occupy, 'erythroid-specific', gene, regulatory, elements])]). relacion([sujeto(['In', 'contrast,', in, postnatal, 'Sf1Cre;', 'Gata4(flox/flox)', 'Gata6(flox/flox)', 'testes,', the, expression, of, the, steroidogenic, markers, 'Star,', 'Cyp11a1,', and, 'Hsd3b6', was, 'increased,', but, a, dramatic, 'down-regulation', of, 'Hsd17b3,', which, is]), verbo([required]), complemento([for, testosterone, 'synthesis,', was, observed])]). relacion([sujeto(['These', data]), verbo([suggest]), complemento([a, lack, of, testis, 'functionality,', with, a, loss, of, normal, steroidogenic, testis, 'function,', concomitant, with, an, expansion, of, the, 'adrenal-like', cell, population, in, postnatal, conditional, double, mutant, testes])]). relacion([sujeto(['These', findings]), verbo([suggest]), complemento([there, are, other, genetic, abnormalities, that, can, lead, to, 'TAM', besides, 'GATA1', mutation, in, the, setting, of, trisomy, 21])]). relacion([sujeto(['Germline', 'GATA1', mutations, that, result, in, the, production, of, an, 'amino-truncated', protein, termed, 'GATA1s', '(', where, s, indicates, 'short)']), verbo([cause]), complemento([congenital, hypoplastic, anemia])]). relacion([sujeto(['In', patients, with, trisomy, 21, ',', similar, somatic, 'GATA1s-producing', mutations]), verbo([promote]), complemento([transient, myeloproliferative, disease, and, acute, megakaryoblastic, leukemia])]). relacion([sujeto(['Here,', we, demonstrate, that]), verbo([induced]), complemento([pluripotent, stem, cells, '(', 'iPSCs)', from, patients, with, 'GATA1-truncating', mutations, exhibit, impaired, erythroid, 'potential,', but, enhanced, megakaryopoiesis, and, 'myelopoiesis,', recapitulating, the, major, phenotypes, of, the, associated, diseases])]). relacion([sujeto(['Similarly,', in, developmentally]), verbo([arrested]), complemento(['GATA1-deficient', murine, 'megakaryocyte-erythroid', progenitors, derived, from, murine, embryonic, stem, cells, '(', 'ESCs),', expression, of, 'GATA1s', promoted, 'megakaryopoiesis,', but, not, erythropoiesis])]). relacion([sujeto(['Transcriptome', analysis, revealed, a, selective, deficiency, in, the, ability, of, 'GATA1s', to]), verbo([activate]), complemento(['erythroid-specific', genes, within, populations, of, hematopoietic, progenitors])]). relacion([sujeto(['Although', its, 'DNA-binding', domain, was, 'intact,', chromatin, immunoprecipitation, studies, showed, that, 'GATA1s']), verbo([binding]), complemento([at, specific, erythroid, regulatory, regions, was, 'impaired,', while, binding, at, many, nonerythroid, 'sites,', including, megakaryocytic, and, myeloid, target, 'genes,', was, normal])]). relacion([sujeto(['Together,', these, observations, indicate, that, 'lineage-specific', 'GATA1', cofactor, associations, are, essential, for, normal, chromatin, occupancy, and]), verbo([provide]), complemento([mechanistic, insights, into, how, 'GATA1s', mutations, cause, human, disease])]). relacion([sujeto(['Among', neonates, with, 'Down', syndrome, '(', 'DS)', and, transient, leukemia, '(', 'TL),', hyperleukocytosis, '(', white, blood, cell, '[', 'WBC]', count, &, 'gt;100', ×, 10, '(', 9, ')', /, 'L)', is]), verbo([associated]), complemento([with, increased, blood, 'viscosity,', respiratory, failure, due, to, pulmonary, 'hypertension,', multiorgan, 'failure,', and, increased, risk, of, early, death])]). relacion([sujeto(['There']), verbo([have]), complemento([been, no, previous, studies, focusing, on, the, effects, of, exchange, transfusion, '(', 'ExT)', on, 'WBC', 'count,', respiratory, 'status,', and, other, parameters, in, 'TL', patients, with, hyperleukocytosis])]). relacion([sujeto(['All', patients]), verbo([required]), complemento([respiratory, support, before, 'ExT'])]). relacion([sujeto(['After', 'ExT,', respiration, status, improved, in, all, five, 'patients:', 'WBC', count, '(', 'mean)']), verbo([decreased]), complemento([by, 85, '%', from, 143, ×, 10, '(', 9, ')', /, 'L', to, 21, ×, 10, '(', 9, ')', /, 'L'])]). relacion([sujeto(['ExT', was, very, effective, in, improving, hyperleukocytosis, and, may]), verbo([have]), complemento([had, favorable, effects, on, respiration])]). relacion([sujeto(['Recent', 'GWAS']), verbo([have]), complemento([revealed, over, 75, loci, associated, with, erythroid, 'traits,', including, the, 4, q27, locus, that, is, associated, with, red, blood, cell, size, '(', mean, corpuscular, 'volume)'])]). relacion([sujeto(['CCNA2', mRNA, is, highly]), verbo([expressed]), complemento([in, human, and, murine, erythroid, progenitor, cells, and, regulated, by, the, essential, erythroid, transcription, factor, 'GATA1'])]). relacion([sujeto(['To', understand, the, role, of, cyclin, 'A2', in, 'erythropoiesis,', we]), verbo([have]), complemento([reduced, expression, of, this, gene, using, short, hairpin, 'RNAs', in, a, primary, murine, erythroid, culture, system])]). relacion([sujeto(['We', demonstrate, that, cyclin, 'A2', levels, affect, erythroid, cell, size, by]), verbo([regulating]), complemento([the, passage, through, cytokinesis, during, the, final, cell, division, of, terminal, erythropoiesis])]). relacion([sujeto(['Our', study]), verbo([provides]), complemento([new, insight, into, cell, cycle, regulation, during, terminal, erythropoiesis, and, more, generally, illustrates, the, value, of, functional, 'GWAS', 'follow-up', to, gain, mechanistic, insight, into, hematopoiesis])]). relacion([sujeto(['Thioredoxin-interacting', protein, '(', 'TXNIP)', is]), verbo([involved]), complemento([in, various, cellular, processes, including, redox, 'control,', 'metabolism,', 'differentiation,', 'growth,', and, apoptosis])]). relacion([sujeto(['With', respect, to, 'hematopoiesis,', 'TXNIP']), verbo([has]), complemento([been, shown, to, play, roles, in, natural, killer, 'cells,', dendritic, 'cells,', and, hematopoietic, stem, cells])]). relacion([sujeto(['We', observed, a, rapid, and, significant]), verbo([increase]), complemento([of, 'TXNIP', transcript, and, protein, levels, in, mouse, erythroleukemia, cells, treated, with, dimethyl, sulfoxide, or, hexamethylene, 'bisacetamide,', inducers, of, erythroid, differentiation])]). relacion([sujeto(['The']), verbo([increase]), complemento([of, 'TXNIP', expression, was, confirmed, in, another, model, of, erythroid, 'differentiation,', 'G1E-ER', 'cells,', which, undergo, differentiation, upon, activation, of, the, 'GATA1', transcription, factor])]). relacion([sujeto(['In', 'addition,', we, showed, that, 'TXNIP', levels, are]), verbo([induced]), complemento([following, inhibition, of, p38, or, 'c-Jun', 'N-terminal', kinase, '(', 'JNK) mitogen-activated', protein, kinases])]). relacion([sujeto(['We', also, observed, an]), verbo([increase]), complemento([in, iron, uptake, and, a, decrease, in, transferrin, receptor, protein, upon, 'TXNIP', 'overexpression,', suggesting, a, role, in, iron, homeostasis])]). relacion([sujeto(['Furthermore,', 'real-time', 'RT-PCR', experiments, showed, that, 'pre-treatment', with, either, 'Resv', or, 'UA']), verbo([suppresses]), complemento([expression, of, 'pro-inflammatory', genes])]). relacion([sujeto(['In', 'conclusion,', our, findings]), verbo([reveal]), complemento([that, 'AA-induced', nephrotoxicities, can, be, attenuated, by, 'pre-treatment', with, either, 'Resv', or, 'UA'])]). relacion([sujeto(['Approximately', 20, '%', -, 30, '%', of, 'TAM', survivors, are, at, risk, of, development, of, acute, myeloid, leukemia, '(', myeloid, leukemia]), verbo([associated]), complemento([with, 'Down', 'syndrome,', 'ML-DS)'])]). relacion([sujeto(['We']), verbo([report]), complemento([unusual, placental, findings, in, a, female, infant, with, trisomy, 21, born, at, 38, weeks, of, gestation])]). relacion([sujeto(['However,', the, 'context-specific', functions]), verbo([associated]), complemento([with, alternative, subunits, remain, largely, unexplored])]). relacion([sujeto(['An', 'erythroid-specific', enhancer]), verbo([mediates]), complemento([transcriptional, activation, of, 'EZH1,', and, a, switch, from, 'GATA2', to, 'GATA1', controls, the, developmental, 'EZH1/2', switch, by, differential, association, with, 'EZH1', enhancers])]). relacion([sujeto(['We', further, examine, the, 'in vivo', stoichiometry, of, the, 'PRC2', complexes, by, quantitative, proteomics, and]), verbo([reveal]), complemento([the, existence, 'of an', 'EZH1-SUZ12', subcomplex, lacking, 'EED'])]). relacion([sujeto(['EZH1', together, with, 'SUZ12', form, a, 'non-canonical', 'PRC2', 'complex,', occupy, active, 'chromatin,', and, positively]), verbo([regulate]), complemento([gene, expression])]). relacion([sujeto(['Loss', of, 'EZH2', expression]), verbo([leads]), complemento([to, repositioning, of, 'EZH1', to, 'EZH2', targets])]). relacion([sujeto(['Thus,', the, 'lineage-', and, developmental, 'stage-specific', regulation, of, 'PRC2', subunit, composition]), verbo([leads]), complemento([to, a, switch, from, canonical, silencing, to, 'non-canonical', functions, during, blood, stem, cell, specification])]). relacion([sujeto(['Laboratories']), verbo([have]), complemento([met, the, challenge, of, transient, and, swiftly, changing, specification, events, from, ventral, mesoderm, through, multipotent, progenitors, and, maturing, 'lineage-restricted', hematopoietic, 'subtypes,', by, developing, powerful, in, vitro, experimental, models, to, interrogate, hematopoietic, ontogeny])]). relacion([sujeto(['Most', 'importantly,', studies, of, differentiating, embryonic, stem, cell, derivatives, in, embryoid, body, and, stromal, coculture, systems]), verbo([have]), complemento([identified, crucial, roles, for, transcription, factor, networks, '(', e])]). relacion([sujeto(['These', and, other, relevant, pathways]), verbo([have]), complemento([pleiotropic, biological, 'effects,', and, are, often, associated, with, early, embryonic, lethality, in, knockout, mice])]). relacion([sujeto(['Further', refinement, in, subsequent, studies]), verbo([has]), complemento([allowed, conditional, expression, of, key, regulatory, 'genes,', and, isolation, of, progenitors, via, cell, surface, markers, '(', e])]). relacion([sujeto(['Despite', numerous, circumstantial, 'evidences,', the, pathogenic, role, of, 'TGF-β', in, primary, myelofibrosis, '(', 'PMF),', the, most, severe, of, the, 'Philadelphia-negative', myeloproliferative, 'neoplasms,', is, still, unclear, because, of, the, modest, '(', 2, -, 'fold)']), verbo([increases]), complemento([in, its, plasma, levels, observed, in, 'PMF', patients, and, in, the, 'Gata1(low)', mouse, model])]). relacion([sujeto(['Whether', myelofibrosis, is]), verbo([associated]), complemento([with, increased, bioavailability, of, 'TGF-β', bound, to, fibrotic, fibres, is, unknown])]). relacion([sujeto(['Additional', 'immuno-TEM', observations, of, spleen, from, 'Gata1(low)', mice, revealed, the, presence, of, numerous]), verbo([activated]), complemento([fibrocytes, establishing, with, their, protrusions, a, novel, cellular, 'interaction,', defined, as, 'peripolesis,', with, megakaryocytes])]). relacion([sujeto(['These', protrusions, infiltrated, the, megakaryocyte, cytoplasm]), verbo([releasing]), complemento([collagen, that, was, eventually, detected, in, its, mature, polymerized, form])]). relacion([sujeto(['Megakaryocytes,', engulfed, with, mature, collagen, 'fibres,', acquired, the, morphology, of, 'para-apoptotic', cells, 'and,', in, the, most, advanced, 'cases,', were]), verbo([recognized]), complemento([as, polylobated, heterochromatic, nuclei, surrounded, by, collagen, fibres, strictly, associated, with, 'TGF-β'])]). relacion([sujeto(['Loss-of-function', studies, indicated, that, peripolesis, between, megakaryocytes, and, fibrocytes]), verbo([required]), complemento([both, 'TGF-β,', possibly, for, inducing, fibrocyte, 'activation,', and, 'P-selectin,', possibly, for, mediating, interaction, between, the, two, cell, types])]). relacion([sujeto(['Loss-of-function', of, 'TGF-β', and, 'P-selectin', also]), verbo([prevented]), complemento([fibrosis])]). relacion([sujeto(['These', observations, identify, that, myelofibrosis, is]), verbo([associated]), complemento([with, pathological, increases, of, 'TGF-β', bioavailability, and, suggest, a, novel, 'megakaryocyte-mediated', mechanism, that, may, increase, 'TGF-β', bioavailability, in, chronic, inflammation])]). relacion([sujeto(['GATA1', is, a, master, regulator, of, 'erythropoiesis,', expression, of, which, is]), verbo([regulated]), complemento([by, multiple, discrete, 'cis-acting', elements])]). relacion([sujeto(['Deletion', of, the, dbGATA, motif]), verbo([led]), complemento([to, significant, reductions, in, 'GFP', expression, in, hematopoietic, 'progenitors,', while, 'GFP', expression, was, maintained, in, erythroblasts])]). relacion([sujeto(['The']), verbo([suppressed]), complemento(['GATA1', expression, was, associated, with, a, compensatory, increase, in, 'GATA2', levels, in, progenitors])]). relacion([sujeto(['When', we, crossed, 'Gata1(ΔdbGATA)', mice, with, 'Gata2', hypomorphic, mutant, mice, '(', 'Gata2(fGN/fGN)', 'mice),', the, 'Gata1(ΔdbGATA)::Gata2(fGN/fGN)', compound, mutant, mice, succumbed, to, a, significant]), verbo([decrease]), complemento([in, the, progenitor, 'population,', whereas, both, groups, of, single, mutant, mice, maintained, progenitors, and, survived, to, 'adulthood,', indicating, the, functional, redundancy, between, 'GATA1', and, 'GATA2', in, progenitors])]). relacion([sujeto(['Meanwhile,', the, effects, of, the, dbGATA, site, deletion, on, 'Gata1', expression, were, subtle, in, 'erythroblasts,', which, showed]), verbo([increased]), complemento(['GATA1', binding, and, enhanced, accumulation, of, active, histone, marks, around, the, 1, 'st-intron', 'GATA', motif, of, the, 'ΔdbGATA', locus])]). relacion([sujeto(['These', results, thus]), verbo([reveal]), complemento([a, novel, role, of, the, dbGATA, motif, in, the, maintenance, of, 'Gata1', expression, in, hematopoietic, progenitors, and, a, functional, compensation, between, the, dbGATA, site, and, the, 1, 'st-intron', 'GATA', motif, in, erythroblasts])]). relacion([sujeto(['Children', with, 'Down', syndrome, '(', 'DS)', are, at]), verbo([increased]), complemento([risk, for, acute, myeloid, leukemias, '(', 'ML-DS)', characterized, by, mixed, megakaryocytic, and, erythroid, phenotype, and, by, acquired, mutations, in, the, 'GATA1', gene, resulting, in, a, short, 'GATA1s', isoform])]). relacion([sujeto(['The', chromosome, 21, microRNA, '(', 'miR)-125b', cluster]), verbo([has]), complemento([been, previously, shown, to, cooperate, with, 'GATA1s', in, transformation, of, fetal, hematopoietic, progenitors])]). relacion([sujeto(['In', this, 'study,', we]), verbo([report]), complemento([that, the, expression, of, 'miR-486-5p', is, increased, in, 'ML-DS', compared, with, 'non-DS', acute, megakaryocytic, leukemias, '(', 'AMKLs)'])]). relacion([sujeto(['miR-486-5p', is]), verbo([regulated]), complemento([by, 'GATA1', and, 'GATA1s', that, bind, to, the, promoter, of, its, host, gene, 'ANK1'])]). relacion([sujeto(['miR-486-5p', is, highly]), verbo([expressed]), complemento([in, mouse, erythroid, precursors, and, knockdown, '(', 'KD)', in, 'ML-DS', cells, reduced, their, erythroid, phenotype])]). relacion([sujeto(['Ectopic', expression, and, 'KD', of, 'miR-486-5p', in, primary, fetal, liver, hematopoietic, progenitors, demonstrated, that, 'miR-486-5p', cooperates, with, 'Gata1s', to]), verbo([enhance]), complemento([their, self, renewal])]). relacion([sujeto(['KLF1', is, an, erythroid, specific, transcription, factor, that]), verbo([binds]), complemento([to, regulatory, regions, of, erythroid, genes])]). relacion([sujeto(['Binding', sites, of, 'KLF1', are, often]), verbo([found]), complemento([near, binding, sites, of, 'GATA-1', and, 'TAL1'])]). relacion([sujeto(['In', the, 'β-globin', 'locus,', 'KLF1', is]), verbo([required]), complemento([for, forming, active, chromatin, 'structure,', although, its, role, is, unclear])]). relacion([sujeto(['To', explore, the, role, of, 'KLF1', in]), verbo([transcribing]), complemento([the, human, 'γ-globin', 'genes,', we, stably, reduced, the, expression, of, 'KLF1', in, erythroid, 'K562', 'cells,', compromising, its, association, in, the, 'β-globin', locus])]). relacion([sujeto(['Interestingly,', 'GATA-1', and, 'TAL1']), verbo([binding]), complemento([was, reduced, in, the, 'β-globin', 'locus,', even, though, their, expressions, were, not, affected, by, 'KLF1', knockdown])]). relacion([sujeto(['The', 'KLF1-dependent', 'GATA-1', and, 'TAL1']), verbo([binding]), complemento([was, observed, in, the, adult, locus, transcribing, the, 'β-globin', gene, and, in, several, erythroid, 'genes,', where, 'GATA-1', occupancy, is, independent, from, 'TAL1'])]). relacion([sujeto(['Simultaneous', analysis, of, multiple, epigenetic, features, in, many, samples, can]), verbo([gain]), complemento([substantial, power, and, specificity, than, analyzing, individual, features, 'and/or', samples, separately])]). relacion([sujeto(['Here,', we, developed, a, novel, approach, to, utilize, the, cooperative, property, of, proteins, to, detect, differential]), verbo([binding]), complemento([given, multivariate, 'ChIP-seq', samples, to, provide, better, 'power,', aiming, for, complementing, existing, approaches, and, providing, new, insights, in, the, method, development, in, this, field])]). relacion([sujeto(['Morphologically,', erythroid, differentiation, proceeds, in, a, nearly, identical, fashion, between, humans, and, 'mice,', but, recent, evidence]), verbo([has]), complemento([shown, that, networks, of, gene, expression, governing, this, process, are, divergent, between, species])]). relacion([sujeto(['Our', analyses]), verbo([suggest]), complemento([that, while, chromatin, structure, across, orthologous, promoters, is, strongly, 'conserved,', subtle, differences, are, associated, with, transcriptional, divergence, between, species])]). relacion([sujeto(['Many', transcription, factor, '(', 'TF)', occupancy, sites, were, poorly]), verbo([conserved]), complemento([across, species, '(', '∼25%', for, 'GATA1,', 'TAL1,', and, 'NFE2)', but, were, more, conserved, between, proerythroblasts, and, cell, lines, derived, from, the, same, species])]). relacion([sujeto(['We']), verbo([found]), complemento([that, certain, 'cis-regulatory', modules, 'co-occupied', by, 'GATA1,', 'TAL1,', and, 'KLF1', are, under, strict, evolutionary, constraint, and, localize, to, genes, necessary, for, erythroid, cell, identity])]). relacion([sujeto(['More', 'generally,', we, show, that]), verbo([conserved]), complemento(['TF', occupancy, sites, are, indicative, of, active, regulatory, regions, and, strong, gene, expression, that, is, sustained, during, maturation])]). relacion([sujeto(['Our', results]), verbo([suggest]), complemento([that, evolutionary, turnover, of, 'TF', binding, sites, associates, with, changes, in, the, underlying, chromatin, 'structure,', driving, transcriptional, divergence])]). relacion([sujeto(['We']), verbo([provide]), complemento([examples, of, how, this, framework, can, be, applied, to, understand, epigenomic, variation, in, specific, regulatory, 'regions,', such, as, the, 'β-globin', gene, locus])]). relacion([sujeto(['Our', findings]), verbo([have]), complemento([important, implications, for, understanding, epigenomic, changes, that, mediate, variation, in, cellular, differentiation, across, 'species,', while, also, providing, a, valuable, resource, for, studies, of, hematopoiesis])]). relacion([sujeto(['We']), verbo([have]), complemento([specifically, ablated, geminin, in, the, developing, murine, hematopoietic, system, and, observed, profound, defects, in, the, generation, of, mature, blood, 'cells,', leading, to, embryonic, lethality])]). relacion([sujeto(['Genome-wide', transcriptome, analysis, identified, key, 'HSC', transcription, factors, as, being, upregulated, upon, geminin, 'deletion,']), verbo([revealed]), complemento([a, gene, network, linked, with, geminin, that, controls, fetal, hematopoiesis])]). relacion([sujeto(['In', order, to, obtain, mechanistic, insight, into, the, ability, of, geminin, to]), verbo([regulate]), complemento(['transcription,', we, examined, 'Hoxa9', as, an, example, of, a, key, gene, in, definitive, hematopoiesis])]). relacion([sujeto(['We', demonstrate, that, in, human, 'K562', cells, geminin, is]), verbo([associated]), complemento([with, 'HOXA9', regulatory, elements, and, its, absence, increases, 'HOXA9', transcription, similarly, to, that, observed, in, vivo])]). relacion([sujeto(['Moreover,', silencing, geminin, reduced, recruitment, of, the, 'PRC2', component, 'SUZ12', to, the, 'HOXA9', locus, and, resulted, in, an]), verbo([increase]), complemento([in, 'RNA', polymerase, 'II', recruitment, and, 'H3K4', trimethylation, '(', 'H3K4me3),', whereas, the, repressive, marks, 'H3K9me3', and, 'H3K27me3', were, reduced])]). relacion([sujeto(['Our', data]), verbo([suggest]), complemento([that, geminin, is, indispensable, for, fetal, hematopoiesis, and, regulates, the, generation, of, a, physiological, pool, of, stem, and, progenitor, cells, in, the, fetal, hematopoietic, system])]). relacion([sujeto(['Children', with, 'Down', syndrome, '(', 'DS)', and, acute, leukemias, acute]), verbo([have]), complemento([unique, 'biological,', 'cytogenetic,', and, intrinsic, factors, that, affect, their, treatment, and, outcome])]). relacion([sujeto(['Myeloid', leukemia, of, 'Down', syndrome, '(', 'ML-DS)', is]), verbo([associated]), complemento([with, high, 'event-free', survival, '(', 'EFS)', rates, and, frequently, preceded, by, a, preleukemia, 'condition,', the, transient, abnormal, hematopoiesis, '(', 'TAM)', present, at, birth])]). relacion([sujeto(['The', disease]), verbo([has]), complemento([been, associated, with, mutations, or, large, deletions, in, 11, ribosomal, protein, genes, including, 'RPS7,', 'RPS10,', 'RPS17,', 'RPS19,', 'RPS24,', 'RPS26,', 'RPS29,', 'RPL5,', 'RPL11,', 'RPL26', and, 'RPL35A', as, well, as, 'GATA1', in, more, than, 50, '%', of, patients])]). relacion([sujeto(['To', identify, new, mutations, responsible, for, 'Diamond-Blackfan', 'anaemia,', we, performed, 'whole-exome', sequencing, analysis, of, 48, patients, with, no, documented, 'mutations/deletions']), verbo([involving]), complemento([known, 'Diamond-Blackfan', anaemia, genes, except, for, 'RPS7,', 'RPL26,', 'RPS29', and, 'GATA1'])]). relacion([sujeto(['Additional', novel, mutations, were]), verbo([found]), complemento([in, eight, 'patients,', including, 'RPL3L,', 'RPL6,', 'RPL7L1T,', 'RPL8,', 'RPL13,', 'RPL14,', 'RPL18A', and, 'RPL31'])]). relacion([sujeto(['In', 'conclusion,', we, identified, novel, germline, mutations, of, two, ribosomal, protein, genes, responsible, for, 'Diamond-Blackfan', 'anaemia,', further, confirming, the, concept, that, mutations, in, ribosomal, protein, genes]), verbo([lead]), complemento([to, 'Diamond-Blackfan', anaemia])]). relacion([sujeto(['X-linked', thrombocytopenia, with, thalassemia, '(', 'XLTT)', is]), verbo([caused]), complemento([by, the, mutation, 216, 'R', &, 'gt;', 'Q', in, exon, 4, of, the, 'GATA1', gene])]). relacion([sujeto(['Additional', comparisons, between, these, disorders, may]), verbo([increase]), complemento([the, understanding, of, mechanisms, behind, 'BM', fibrosis, in, relation, to, pathological, megakaryopoiesis])]). relacion([sujeto(['Mitosis', entails, global, alterations, to, chromosome, structure, and]), verbo([nuclear]), complemento(['architecture,', concomitant, with, transient, silencing, of, transcription])]). relacion([sujeto(['While', many]), verbo([nuclear]), complemento([factors, dissociate, from, mitotic, 'chromosomes,', the, observation, that, certain, nuclear, factors, and, chromatin, features, remain, associated, with, individual, loci, during, mitosis, originated, the, hypothesis, that, such, mitotically, retained, molecular, signatures, could, provide, transcriptional, memory, through, mitosis])]). relacion([sujeto(['However,', mitotic, chromatin, accessibility, is, locally, 'dynamic,', with, individual, loci]), verbo([maintaining]), complemento(['none,', 'some,', or, all, of, their, interphase, accessibility])]). relacion([sujeto(['Mitotic', reduction, in, accessibility, occurs, primarily, within, 'narrow,', highly, 'DNase', hypersensitive, sites, that, frequently, coincide, with, transcription, factor]), verbo([binding]), complemento(['sites,', whereas, broader, domains, of, moderate, accessibility, tend, to, be, more, stable])]). relacion([sujeto(['In', 'mitosis,', proximal, promoters, generally]), verbo([maintain]), complemento([their, accessibility, more, 'strongly,', whereas, distal, regulatory, elements, tend, to, lose, accessibility])]). relacion([sujeto(['Large', domains, of, 'DNA', hypomethylation, mark, a, subset, of, promoters, that]), verbo([retain]), complemento([accessibility, during, mitosis, and, across, many, cell, types, in, interphase])]). relacion([sujeto(['Erythroid', transcription, factor, 'GATA1', exerts, 'site-specific', changes, in, interphase, accessibility, that, are, most, pronounced, at, distal, regulatory, 'elements,', but]), verbo([has]), complemento([little, influence, on, mitotic, accessibility])]). relacion([sujeto(['We', conclude, that, features, of, open, chromatin, are, remarkably, stable, through, 'mitosis,', but, are]), verbo([modulated]), complemento([at, the, level, of, individual, genes, and, regulatory, elements])]). relacion([sujeto(['Moreover,', 'viral-mediated', expression, of, 'hGATA-1', and, 'hGATA-2', in, the, dorsal, hippocampus]), verbo([caused]), complemento(['depressive-like', deficits, in, the, forced, swim, test, and, learned, helplessness, models, of, 'depression,', and, decreased, the, expression, of, several, 'synapse-related', genes, as, well, as, spine, number, in, hippocampal, neurons])]). relacion([sujeto(['Conversely,', shRNA, knockdown, of, 'GATA-2']), verbo([increased]), complemento(['synapse-related', gene, 'expression,', spine, 'number,', and, dendrite, branching])]). relacion([sujeto(['The', results, demonstrate, that, 'hGATA-1', and, 'hGATA-2', expression, in, hippocampus, is, sufficient, to]), verbo([cause]), complemento([depressive, like, behaviors, that, are, associated, with, reduction, in, spine, synapse, density, and, expression, of, 'synapse-related', genes])]). relacion([sujeto(['We', identified, a, 'robust,', 'genome-wide', mechanism, of, 'MEG-specific', lineage, priming, by, a, previously, described, 'stem/progenitor', 'cell-expressed', transcription, factor, heptad, '(', 'GATA2,', 'LYL1,', 'TAL1,', 'FLI1,', 'ERG,', 'RUNX1,', 'LMO2)']), verbo([binding]), complemento([to, 'MEG-associated', 'cis-regulatory', modules, '(', 'CRMs)', in, multipotential, progenitors])]). relacion([sujeto(['This', is, followed, by, 'genome-wide', 'GATA', factor, switching, that]), verbo([mediates]), complemento([further, induction, of, 'MEG-specific', genes, following, lineage, commitment])]). relacion([sujeto(['Our', findings]), verbo([reveal]), complemento([important, new, insights, into, how, 'ERY', and, 'MEG', lineages, arise, from, a, common, bipotential, progenitor, via, overlapping, and, divergent, functions, of, shared, hematopoietic, transcription, factors])]). relacion([sujeto(['We']), verbo([found]), complemento([that, sites, of, occupancy, shift, dramatically, during, commitment, to, the, erythroid, 'lineage,', vary, further, during, terminal, 'maturation,', and, are, strongly, associated, with, changes, in, gene, expression])]). relacion([sujeto(['In', multilineage, 'progenitors,', the, likely]), verbo([target]), complemento([genes, are, enriched, for, hematopoietic, growth, and, functions, associated, with, the, mature, cells, of, specific, daughter, lineages, '(', such, as, 'megakaryocytes)'])]). relacion([sujeto(['In', 'contrast,']), verbo([target]), complemento([genes, in, erythroblasts, are, specifically, enriched, for, red, cell, functions])]). relacion([sujeto(['Furthermore,', shifts, in, 'TAL1', occupancy, during, erythroid, differentiation, are]), verbo([associated]), complemento([with, gene, repression, '(', 'dissociation)', and, induction, '(', 'co-occupancy', with, 'GATA1)'])]). relacion([sujeto(['Based', on, both, enrichment, for, transcription, factor]), verbo([binding]), complemento([site, motifs, and, 'co-occupancy', determined, by, 'ChIP-seq,', recruitment, by, 'GATA', transcription, factors, appears, to, be, a, stronger, determinant, of, 'TAL1', binding, to, chromatin, than, the, canonical, 'E-box', binding, site, motif])]). relacion([sujeto(['Studies', of, additional, proteins]), verbo([lead]), complemento([to, the, model, that, 'TAL1', regulates, expression, after, being, directed, to, a, distinct, subset, of, genomic, binding, sites, in, each, cell, type, via, its, association, with, different, complexes, containing, master, regulators, such, as, 'GATA2,', 'ERG,', and, 'RUNX1', in, multilineage, cells, and, the, 'lineage-specific', master, regulator, 'GATA1', in, erythroblasts])]). relacion([sujeto(['However,', there, is, substantial, 'inter-individual', variation, in, hepatic, gene, 'expression,', and, although, numerous, genetic, factors]), verbo([have]), complemento([been, 'identified,', less, is, known, about, the, epigenetic, factors])]). relacion([sujeto(['By', analyzing, the, methylomes, and, transcriptomes, of, 14, fetal, and, 181, adult, 'livers,', we, identified, 657, differentially, methylated, genes, with, 'adult-specific', 'expression,', these, genes, were, enriched, for, transcription, factor]), verbo([binding]), complemento([sites, of, 'HNF1A', and, 'HNF4A'])]). relacion([sujeto(['We', also, identified, 1, ',', 0, genes, specific, to, fetal, 'liver,', which, were, enriched, for, 'GATA1,', 'STAT5A,', 'STAT5B', and, 'YY1']), verbo([binding]), complemento([sites])]). relacion([sujeto(['Of', the, 526, unique, eQTL]), verbo([associated]), complemento(['genes,', 293, correlated, significantly, not, only, with, genetic, variation, but, also, with, methylation, levels])]). relacion([sujeto(['Our', analyses, generated, a, comprehensive, resource, of, factors]), verbo([involved]), complemento([in, the, regulation, of, hepatic, gene, 'expression,', and, allowed, us, to, estimate, the, proportion, of, variation, in, gene, expression, that, could, be, attributed, to, genetic, and, epigenetic, 'variation,', both, crucial, to, understanding, differences, in, drug, response, and, the, etiology, of, liver, diseases])]). relacion([sujeto(['Approximately', 25, '%', of, 'DBA', patients]), verbo([have]), complemento([a, mutation, in, 'RPS19,', which, encodes, a, component, of, the, 40, 'S', ribosomal, subunit])]). relacion([sujeto(['We']), verbo([found]), complemento([that, 'RPS19', deficiency, in, hematopoietic, progenitor, cells, leads, to, decreased, 'GATA1', expression, in, the, erythroid, progenitor, population, and, 'p53-dependent', upregulation, of, tumor, necrosis, 'factor-α', '(', 'TNF-α)', in, nonerythroid, cells])]). relacion([sujeto(['The']), verbo([decrease]), complemento([in, 'GATA1', expression, was, 'mediated,', at, least, in, 'part,', by, activation, of, p38, 'MAPK', in, erythroid, cells, and, rescued, by, inhibition, of, 'TNF-α', or, p53])]). relacion([sujeto(['Our', data]), verbo([reveal]), complemento([that, 'RPS19', deficiency, leads, to, 'inflammation,', 'p53-dependent', increase, in, 'TNF-α,', activation, of, p38, 'MAPK,', and, decreased, 'GATA1', 'expression,', suggesting, a, novel, mechanism, for, the, erythroid, defects, observed, in, 'DBA'])]). relacion([sujeto(['Metastasis', is, the, main]), verbo([cause]), complemento([of, 'cancer-related', death, and, thus, understanding, the, molecular, and, cellular, mechanisms, underlying, this, process, is, critical])]). relacion([sujeto(['Here,', our, data, 'demonstrate,', contrary, to, established, 'dogma,', that]), verbo([loss]), complemento([of, 'haematopoietic-derived', focal, adhesion, kinase, '(', 'FAK)', is, sufficient, to, enhance, tumour, metastasis])]). relacion([sujeto(['Using', both, experimental, and, spontaneous, metastasis, 'models,', we, show, that, genetic, ablation, of, haematopoietic, 'FAK', does, not, affect, primary, tumour, growth, but]), verbo([enhances]), complemento([the, incidence, of, metastasis, significantly])]). relacion([sujeto(['At', a, molecular, 'level,', haematopoietic, 'FAK', deletion, results, in, an]), verbo([increase]), complemento([in, 'PU-1', levels, and, decrease, in, 'GATA-1', levels, causing, a, shift, of, hematopoietic, homeostasis, towards, a, myeloid, commitment])]). relacion([sujeto(['The', subsequent]), verbo([increase]), complemento([in, circulating, granulocyte, 'number,', with, an, increase, in, serum, 'CXCL12', and, granulocyte, 'CXCR4', 'levels,', was, required, for, augmented, metastasis, in, mice, lacking, haematopoietic, 'FAK'])]). relacion([sujeto(['Overall', our, findings]), verbo([provide]), complemento([a, mechanism, by, which, haematopoietic, 'FAK', controls, cancer, metastasis])]). relacion([sujeto(['Somatic', 'GATA1', mutations, are, believed, to, be, pivotal, in, the, development, of, transient, abnormal, myelopoiesis, and]), verbo([have]), complemento([proven, to, be, a, marker, of, clonal, identity, in, its, evolution, to, megakaryoblastic, leukemia])]). relacion([sujeto(['GATA1', mutations, are]), verbo([found]), complemento([almost, exclusively, in, children, with, myeloid, proliferations, related, to, 'Down', syndrome, '(', 'DS)'])]). relacion([sujeto(['Here,', we]), verbo([report]), complemento([two, phenotypically, and, cytogenetically, normal, children, with, acute, megakaryoblastic, leukemia, '(', 'AMKL)', whose, blasts, had, both, acquired, trisomy, 21, and, 'GATA1', mutation])]). relacion([sujeto(['Following', spontaneous, improvement, of, the, 'disease,', leukemic, blasts]), verbo([increased]), complemento([7, &, 'nbsp;months', later])]). relacion([sujeto(['He', received, less, intensive, 'chemotherapy,', and]), verbo([he]), complemento([is, now, 6, &, 'nbsp;years', old, in, complete, remission])]). relacion([sujeto(['Although']), verbo([he]), complemento([received, intensive, chemotherapy, and, a, cord, blood, 'transplantation,', he, died, without, gaining, remission])]). relacion([sujeto(['Based', on, a, literature, 'review,', we, identified]), verbo([reports]), complemento([describing, 14, 'non-DS', 'AMKL', with, 'GATA1', mutation, and, acquired, trisomy, 21])]). relacion([sujeto(['These', cases]), verbo([suggest]), complemento([that, 'GATA1', mutation, may, cooperate, with, the, additional, chromosome, 21, in, developing, myeloid, proliferations, even, in, 'non-DS', patients])]). relacion([sujeto(['Congenital', erythropoietic, porphyria, '(', 'CEP)', is, a, rare, genetic, disease, that, is, characterized, by, a, severe, cutaneous, photosensitivity]), verbo([causing]), complemento([unrecoverable, 'deformities,', chronic, hemolytic, anemia, requiring, blood, transfusion, 'program,', and, by, fatal, systemic, complications])]). relacion([sujeto(['A', correct, and, early, diagnosis, is]), verbo([required]), complemento([to, develop, a, management, plan, that, is, appropriate, to, the, 'patient\'s', needs])]). relacion([sujeto(['Here,', we]), verbo([have]), complemento([characterized, two, novel, 'X-linked', 'CEP', 'patients,', both, with, misleading, hematological, phenotypes, that, include, dyserythropoietic, 'anemia,', 'thrombocytopenia,', and, hereditary, persistence, of, fetal, hemoglobin])]). relacion([sujeto(['We', compare, the, previously]), verbo([reported]), complemento([case, to, ours, and, propose, a, diagnostic, paradigm, for, this, variant, of, 'CEP'])]). relacion([sujeto(['Congenital', myeloproliferative, disorders, and, transient, leukemic, disorders]), verbo([have]), complemento([been, described, in, the, perinatal, period, in, infants, with, trisomy, 21, '(', 'Down', 'syndrome)'])]). relacion([sujeto(['We']), verbo([report]), complemento([a, novel, case, of, a, neonate, with, trisomy, 21, with, 'GATA1-mutated', congenital, myeloproliferative, disorder, complicated, by, placental, fetal, thrombotic, vasculopathy, featuring, chorionic, vessel, leukemic, 'thrombi,', fetal, circulation, vascular, 'injuries,', and, large, aggregates, of, avascular, villi])]). relacion([sujeto(['These', thrombotic, and, vasculopathic, changes, within, the, placenta, are, likely, a, reflection, of, the, hypercoagulable, state]), verbo([caused]), complemento([by, the, myeloproliferative, disorder])]). relacion([sujeto(['Placental', fetal, thrombotic, vasculopathy, is]), verbo([associated]), complemento([with, adverse, outcomes, for, the, 'infant,', and, should, be, documented, during, formal, pathological, examination, of, the, placenta])]). relacion([sujeto(['GATA-1', mutations]), verbo([have]), complemento([been, associated, with, various, 'diseases,', such, as, 'X-linked', thrombocytopenia])]). relacion([sujeto(['ALAS2', is, an, 'X-linked', 'erythroid-specific', isoenzyme]), verbo([expressed]), complemento([during, erythropoiesis])]). relacion([sujeto(['Mutations', of, 'ALAS2', were]), verbo([associated]), complemento([with, 'X-linked', sideroblastic, anemia])]). relacion([sujeto(['We']), verbo([report]), complemento([a, case, of, newborn, twin, boy, with, anemia, and, thrombocytopenia, at, birth])]). relacion([sujeto(['Gene', sequencing, study, showed, a, previously]), verbo([reported]), complemento([mutation, in, 'GATA-1', at, c])]). relacion([sujeto(['Children', with, 'Down', syndrome, '(', 'DS)', are, at, a, substantially]), verbo([increased]), complemento([risk, to, develop, acute, myeloid, leukemia, '(', 'AML)'])]). relacion([sujeto(['This']), verbo([increase]), complemento([in, incidence, is, 'tempered,', 'however,', by, favorable, overall, survival, rates, of, approximately, 80, '%', ',', whereas, survival, for, 'non-DS', children, with, similar, leukemic, subtypes, is, &, 'lt;35%'])]). relacion([sujeto(['In', this, 'review,', the, clinical, studies, that]), verbo([have]), complemento([contributed, to, this, overall, high, survival, will, be, presented, and, their, individual, successes, will, be, discussed])]). relacion([sujeto(['While', we]), verbo([have]), complemento([considerable, understanding, of, the, transcriptional, networks, controlling, mammalian, cell, 'differentiation,', our, knowledge, of, posttranscriptional, regulatory, events, is, very, limited])]). relacion([sujeto(['Using', differentiation, of, primary, erythroid, cells, as, a, 'model,', we, show, 'that the', 'sequence-specific', 'mRNA-binding', protein, 'Cpeb4', is, strongly]), verbo([induced]), complemento([by, the, 'erythroid-important', transcription, factors, 'Gata1', and, 'Tal1', and, is, essential, for, terminal, erythropoiesis])]). relacion([sujeto(['By']), verbo([interacting]), complemento([with, the, translation, initiation, factor, 'eIF3,', 'Cpeb4', represses, the, translation, of, a, large, set, of, 'mRNAs,', including, its, own, mRNA])]). relacion([sujeto(['Thus,', transcriptional, induction, and, translational, repression, combine, to, form, a, negative, feedback, loop, to, control, 'Cpeb4', protein, levels, within, a, specific, range, that, is]), verbo([required]), complemento([for, terminal, erythropoiesis])]). relacion([sujeto(['Our', study]), verbo([provides]), complemento([an, example, of, how, translational, control, is, integrated, with, transcriptional, regulation, to, precisely, control, gene, expression, during, mammalian, cell, differentiation])]). relacion([sujeto(['Expanded', knowledge, of, the, molecular, control, of, hemoglobin, synthesis, will]), verbo([provide]), complemento([a, basis, for, rational, design, of, therapies, for, 'β-hemoglobinopathies'])]). relacion([sujeto(['Here,', we, utilize, 'UCB-CD34+', stem, cells]), verbo([induced]), complemento([to, undergo, erythroid, differentiation, to, characterize, the, transcriptome, and, transcription, factor, networks, '(', 'TFNs)', associated, with, the, 'γ/β-globin', switch, during, fetal, erythropoiesis])]). relacion([sujeto(['To']), verbo([gain]), complemento([insights, into, transcription, factors, involved, in, globin, gene, 'regulation,', microarray, analysis, was, performed, on, 'RNA', isolated, from, 'UCB-CD34+', 'cell-derived', erythroid, progenitors, harvested, on, day, 21, ',', 42, ',', 49, and, 56, using, the, 'HumanHT-12', 'Expression', 'BeadChip'])]). relacion([sujeto(['Forty-five', 'TFs', were, silenced, by, day, 56, '(', 'Profile-1)', and, 30, 'TFs', were]), verbo([activated]), complemento([by, day, 56, '(', 'Profile-2)'])]). relacion([sujeto(['GATA-1(low/low)', mice]), verbo([have]), complemento([an, increase, in, megakaryocytes, '(', 'MKs)', and, trabecular, bone])]). relacion([sujeto(['The', latter, is, thought, to, result, from, 'MKs', directly]), verbo([stimulating]), complemento([osteoblastic, bone, formation, while, simultaneously, inhibiting, osteoclastogenesis])]). relacion([sujeto(['Osteoprotegerin', '(', 'OPG)', is, known, to]), verbo([inhibit]), complemento([osteoclastogenesis, and, 'OPG(-/-)', mice, have, reduced, trabecular, and, cortical, bone, due, to, increased, osteoclastogenesis])]). relacion([sujeto(['Interestingly,', 'GATA-1(low/low)', mice]), verbo([have]), complemento([increased, 'OPG', levels])]). relacion([sujeto(['GATA-1(low/low)', ×, 'OPG(-/-)', mice]), verbo([have]), complemento([increased, cortical, bone, 'porosity,', similar, to, 'OPG(-/-)', mice])]). relacion([sujeto(['Both', 'OPG(-/-)', and, 'GATA-1(low/low)', ×, 'OPG(-/-)', 'mice,', were]), verbo([found]), complemento([to, have, increased, osteoclasts, localized, to, cortical, 'bone,', possibly, producing, the, observed, elevated, porosity])]). relacion([sujeto(['Notably,', 'GATA-1(low/low)', ×, 'OPG(-/-)', mice, had, trabecular, bone, parameters, that, were, not, different, from, 'C57BL/6', 'values,']), verbo([suggesting]), complemento([that, 'GATA-1', deficiency, can, partially, rescue, the, trabecular, bone, loss, observed, with, 'OPG', deficiency])]). relacion([sujeto(['The', fact, that, 'GATA-1', deficiency, appears, to, be, able, to, partially, rescue, the, 'trabecular,', but, not, the, cortical, bone, phenotype]), verbo([suggests]), complemento([that, 'MKs', can, locally, enhance, trabecular, bone, 'volume,', but, that, 'MK', secreted, factors, cannot, access, cortical, bone, sufficiently, to, inhibit, osteoclastogenesis, or, that, 'OPG', itself, is, required, to, inhibit, osteoclastogenesis, in, cortical, bone])]). relacion([sujeto(['To', verify, 'Ig', diversity, achieved, during, the, production, of, 'B', 'cells,', 'V(D)J', segments, were, sequenced, in, primary, lymphoid, organs, of, the, equine, fetus, and, adult, 'horse,']), verbo([revealed]), complemento([that, similar, heavy, chain, 'VDJ', segments, and, 'CDR3', lengths, were, most, frequently, used, independent, of, life, stage])]). relacion([sujeto(['Our', data]), verbo([suggest]), complemento([that, the, 'B', cells, produced, in, the, liver, and, bone, marrow, of, the, equine, fetus, generate, a, wide, repertoire, of, 'pre-immune', 'Igs', for, 'protection,', and, the, more, diverse, use, of, different, lambda, variable, gene, segments, in, fetal, life, may, provide, the, neonate, an, opportunity, to, respond, to, a, wider, range, of, antigens, at, birth])]). relacion([sujeto(['A', 'GATA1', mutation]), verbo([leading]), complemento([to, the, production, of, 'N-terminally', truncated, 'GATA1', '(', 'GATA1s)', in, early, 'megakaryocyte/erythroid', progenitors, is, linked, to, the, onset, of, 'TAM', and, cooperated, with, the, effect, of, trisomy, 21, '(', 'Ts21)'])]). relacion([sujeto(['To']), verbo([gain]), complemento([insights, into, the, underlying, mechanisms, of, the, progression, to, 'TAM', in, 'DS', 'patients,', we, generated, human, pluripotent, stem, cells, harbouring, 'Ts21', 'and/or', 'GATA1s', by, combining, 'microcell-mediated', chromosome, transfer, and, genome, editing, technologies])]). relacion([sujeto(['Thus,', the, 'DS', model, cells, generated, by, these, two, technologies, are, useful, in, assessing, how, 'GATA1s', mutation, is]), verbo([involved]), complemento([in, the, onset, of, 'TAM', in, patients, with, 'DS'])]). relacion([sujeto(['β-Thalassaemia', major, '(', 'β-TM)', is, an, inherited, haemoglobinopathy]), verbo([caused]), complemento([by, a, quantitative, defect, in, the, synthesis, of, 'β-globin', chains, of, 'haemoglobin,', leading, to, the, accumulation, of, free, 'α-globin', chains, that, form, toxic, aggregates])]). relacion([sujeto(['Despite', extensive, knowledge, of, the, molecular, defects]), verbo([causing]), complemento(['β-TM,', little, is, known, of, the, mechanisms, responsible, for, the, ineffective, erythropoiesis, observed, in, the, 'condition,', which, is, characterized, by, accelerated, erythroid, 'differentiation,', maturation, arrest, and, apoptosis, at, the, polychromatophilic, stage])]). relacion([sujeto(['We']), verbo([have]), complemento([previously, demonstrated, that, normal, human, erythroid, maturation, requires, a, transient, activation, of, 'caspase-3', at, the, later, stages, of, maturation])]). relacion([sujeto(['We']), verbo([have]), complemento([shown, 'that,', in, human, 'erythroblasts,', the, chaperone, heat, shock, protein70, '(', 'HSP70)', is, constitutively, expressed, 'and,', at, later, stages, of, 'maturation,', translocates, into, the, nucleus, and, protects, 'GATA-1', from, 'caspase-3', cleavage])]). relacion([sujeto(['The', primary, role, of, this, ubiquitous, chaperone, is, to]), verbo([participate]), complemento([in, the, refolding, of, proteins, denatured, by, cytoplasmic, 'stress,', thus, preventing, their, aggregation])]). relacion([sujeto(['Here', we, show, in, vitro, that, during, the, maturation, of, human, 'β-TM', 'erythroblasts,', 'HSP70']), verbo([interacts]), complemento([directly, with, free, 'α-globin', chains])]). relacion([sujeto(['As', a, 'consequence,', 'HSP70', is, sequestrated, in, the, cytoplasm, and, 'GATA-1', is, no, longer, 'protected,', resulting, in, 'end-stage', maturation]), verbo([arrest]), complemento([and, apoptosis])]). relacion([sujeto(['Transduction', of, a, 'nuclear-targeted', 'HSP70', mutant, or, a, 'caspase-3-uncleavable', 'GATA-1', mutant, restores, terminal, maturation, of, 'β-TM', 'erythroblasts,', which, may]), verbo([provide]), complemento([a, rationale, for, new, targeted, therapies, of, 'β-TM'])]). relacion([sujeto(['TAM', is]), verbo([caused]), complemento([by, cooperation, between, cT21, and, acquired, somatic, 'N-terminal', truncating, mutations, in, the, key, haematopoietic, transcription, factor, 'GATA1'])]). relacion([sujeto(['These', 'mutations,', which, are, not, leukaemogenic, in, the, absence, of, 'cT21,', are]), verbo([found]), complemento([in, almost, 'one-third', of, neonates, with, 'DS'])]). relacion([sujeto(['Although', studies, in, mouse, models]), verbo([have]), complemento([suggested, a, pathogenic, role, of, deregulated, expression, of, several, chromosome, 21, -, encoded, 'genes,', their, role, in, human, leukaemogenesis, remains, unclear])]). relacion([sujeto(['Wogonin,', a, flavonoid, derived, from, 'Scutellaria', baicalensis, 'Georgi,']), verbo([has]), complemento([been, demonstrated, to, be, highly, effective, in, treating, hematologic, malignancies])]). relacion([sujeto(['Wogonin', 'up-regulated', transcription, factor, 'GATA-1', and]), verbo([enhanced]), complemento([binding, between, 'GATA-1', and, 'FOG-1,', thereby, increasing, expression, of, 'erythroid-differentiation', genes])]). relacion([sujeto(['Wogonin', also, 'up-regulated', the, expression, of, p21, and]), verbo([induced]), complemento([cell, cycle, arrest])]). relacion([sujeto(['Studies', employing, benzidine, staining, and, analyses, of, cell, surface, markers, glycophorin, 'A', '(', 'GPA)', and, 'CD71', indicated, that, wogonin]), verbo([promoted]), complemento([differentiation, of, 'K562,', 'imatinib-resistant', 'K562,', and, primary, 'patient-derived', 'CML', cells])]). relacion([sujeto(['Wogonin', also]), verbo([enhanced]), complemento([binding, between, 'GATA-1', and, 'MEK,', resulting, in, inhibition, of, the, growth, of, 'CML', cells])]). relacion([sujeto(['Additionally,', in, vivo, studies, showed, that, wogonin]), verbo([decreased]), complemento([the, number, of, 'CML', cells, and, prolonged, survival, of, 'NOD/SCID', mice, injected, with, 'K562', and, 'imatinib-resistant', 'K562', cells])]). relacion([sujeto(['These', data]), verbo([suggested]), complemento([that, wogonin, induces, cycle, arrest, and, erythroid, differentiation, in, vitro, and, inhibits, proliferation, in, vivo])]). relacion([sujeto(['Although', transcription, factor]), verbo([binding]), complemento([events, show, substantial, variation, across, 'species,', most, computational, approaches, to, study, regulatory, elements, focus, primarily, upon, highly, conserved, 'sites,', and, rely, heavily, upon, multiple, sequence, alignments])]). relacion([sujeto(['However,', sequence, conservation, based, approaches]), verbo([have]), complemento([limited, ability, to, detect, 'lineage-specific', elements, that, could, contribute, to, 'species-specific', traits])]). relacion([sujeto(['In', this, 'paper,', we, describe, a, novel, framework, that, utilizes, a, 'birth-death', model, to, trace, the, evolution, of, 'lineage-specific']), verbo([binding]), complemento([sites, without, relying, on, detailed, 'base-by-base', 'cross-species', alignments])]). relacion([sujeto(['Our', model, was, applied, to, analyze, the, evolution, of]), verbo([binding]), complemento([sites, based, on, the, 'ChIP-seq', data, for, six, transcription, factors, '(', 'GATA1,', 'SOX2,', 'CTCF,', 'MYC,', 'MAX,', 'ETS1)', along, the, lineage, toward, human, after, 'human-mouse', common, ancestor])]). relacion([sujeto(['We', estimate, that, a, substantial, fraction, of]), verbo([binding]), complemento([sites, '(', '∼58-79%', for, each, 'factor)', in, humans, have, origins, since, the, divergence, with, mouse])]). relacion([sujeto(['Over', 15, '%', of, all]), verbo([binding]), complemento([sites, are, unique, to, hominids])]). relacion([sujeto(['Such', elements, are, often, enriched, near, genes]), verbo([associated]), complemento([with, specific, 'pathways,', and, harbor, more, common, 'SNPs', than, older, binding, sites, in, the, human, genome])]). relacion([sujeto(['Firstly,', the, differentially]), verbo([expressed]), complemento([genes, '(', 'DEGs)', were, obtained, with, the, thresholds, of, '|', 'logFC|>1'])]). relacion([sujeto(['Secondly,', pathway, enrichment, analysis, for, 'DCGs', was, performed, by, the, 'Database', for, 'Annotation,', 'Visualization', and, 'Integrated', 'Discovery', and, the, 'DCLs']), verbo([associated]), complemento([with, 'RA', were, selected, by, comparing, the, obtained, 'DCLs', with, known, transcription, factor, '(', 'TF)-targets', in, the, 'TRANSFAC', database])]). relacion([sujeto(['A', number, of, 'TF-target', relations, in, the, constructed, network, were, not, within, 'DCLs', when, the, 'TF', and]), verbo([target]), complemento([gene, were, 'DCGs'])]). relacion([sujeto(['The', identified, 'TFs', may]), verbo([have]), complemento([an, important, role, in, the, pathogenesis, of, 'RA', and, have, the, potential, to, be, used, as, biomarkers, for, the, development, of, novel, diagnostic, and, therapeutic, strategies, for, 'RA'])]). relacion([sujeto(['Previously,', we, described, a, role, for, the, master, regulator, of, 'erythropoiesis,', 'GATA-1,', in]), verbo([inducing]), complemento([genes, encoding, components, of, the, autophagy, machinery])]). relacion([sujeto(['GATA-1/Foxo3', repressed, expression, of, 'Exosc8,', a, pivotal, component, of, the, exosome, 'complex,', which]), verbo([mediates]), complemento(['RNA', surveillance, and, epigenetic, regulation])]). relacion([sujeto(['Strikingly,', downregulating, 'Exosc8,', or, additional, exosome, complex, 'components,', in, primary, erythroid, precursor, cells]), verbo([induced]), complemento([erythroid, cell, maturation])]). relacion([sujeto(['We', identified, known, critical, 'genes,', such, as, 'HBD', and, 'GATA1,', and, functional, connections, during, erythropoiesis, using, these, dynamic, 'networks,', while, the, traditional, static, network, was, not, able, to]), verbo([provide]), complemento([such, information])]). relacion([sujeto(['Docking', protein, 2, '(', 'Dok2)', is, an, adapter, protein, which, is]), verbo([involved]), complemento([in, hematopoiesis])]). relacion([sujeto(['To', address, this, 'issue,', we, 'knocked-down', 'Dok2', mRNA, in, mouse, erythroleukemia, cells, which, highly]), verbo([express]), complemento(['Dok2', intrinsically])]). relacion([sujeto(['Mouse', erythroleukemia, cells, were, transfected, with, 'Dok2', siRNA, for, 24, h, and, gene, expression, of, erythroid, 'differentiation-related', 'genes,', such, as, 'GATA']), verbo([binding]), complemento([protein, 1, '(', 'Gata1),', 'Krüppel-like', factor, 1, '(', 'Klf1),', 'α-globin', and, 'β-globin', were, assessed, by, 'real-time', polymerase, chain, reaction])]). relacion([sujeto(['Among', the, tested, 'genes,', expression, of, 'Klf1', exhibited, a, 1.94, -, fold]), verbo([increase]), complemento([when, compared, to, the, control, 24, h, after, transfection])]). relacion([sujeto(['Immunocytochemistry', and, chromatin, immunoprecipitation, assays, revealed, that, 'Dok2', protein, localizes, in, the, nucleus, and]), verbo([binds]), complemento([to, the, promoter, region, of, 'Klf1', gene])]). relacion([sujeto(['Dok2', is, able, to, control, 'Klf1', expression, by, transcriptional, regulation, through, directly]), verbo([binding]), complemento([to, its, promoter, region])]). relacion([sujeto(['Their', implementation, in, therapy, will]), verbo([require]), complemento([standards, for, quality, 'control,', including, appropriate, selection, criteria, for, functional, analysis, and, efficacy, determination])]). relacion([sujeto(['NB4', and, 'MV-4-11']), verbo([express]), complemento([high, levels, of, 'CCAAT/enhancer-binding', 'protein-alpha', '(', 'CEBPα)', and, differentiate, from, myeloblasts, to, 'pro-monocytes', and, 'myeloblasts,', respectively])]). relacion([sujeto(['Our', study, gives, a, useful, guideline, of, standards, for, appropriate, usage, of, leukemia, cell, lines, for, examining, novel]), verbo([targets]), complemento([in, vitro])]). relacion([sujeto(['Growth', factor, independence, 1, '(', 'Gfi-1)', is, a, part, of, the, transcriptional, network, that]), verbo([regulates]), complemento([the, development, of, adult, hematopoietic, stem, and, progenitor, cells])]). relacion([sujeto(['Gfi-1-null', '(', 'Gfi-1(-/-))', mice]), verbo([have]), complemento([reduced, numbers, of, hematopoietic, stem, cells, '(', 'HSCs),', impaired, radioprotective, function, of, hematopoietic, progenitor, cells, '(', 'HPCs),', and, myeloid, and, erythroid, hyperplasia])]). relacion([sujeto(['We']), verbo([found]), complemento([that, the, development, of, 'HPCs', and, 'erythropoiesis,', but, not, 'HSC', 'function,', was, rescued, by, reducing, the, expression, of, inhibitor, of, 'DNA-binding', protein, 2, '(', 'Id2)', in, 'Gfi-1(-/-)', mice])]). relacion([sujeto(['Reduction', of, 'Id2', expression, in, 'Gfi-1(-/-)', mice]), verbo([increased]), complemento([the, expression, of, 'Gata1,', 'Eklf,', and, 'EpoR,', which, are, required, for, proper, erythropoiesis])]). relacion([sujeto(['These', data]), verbo([provide]), complemento([new, evidence, that, 'Gfi-1', is, linked, to, the, erythroid, gene, regulatory, network, by, repressing, 'Id2', expression])]). relacion([sujeto(['α-Synuclein', is, highly]), verbo([expressed]), complemento([in, neural, tissue, and, during, 'erythropoiesis,', where, the, key, erythroid, regulator, 'GATA1', has, been, found, to, modulate, its, expression])]). relacion([sujeto(['While', specific, 'α-synuclein', '(', 'SNCA)', mutations, are, known, to]), verbo([cause]), complemento([autosomal, dominant, familial, 'Parkinson\'s', 'disease,', its, 'wild-type', function, remains, under, debate])]). relacion([sujeto(['Our', findings, show, that, while, bone, marrow, and, spleen, erythropoiesis, and, peripheral, blood, erythrocyte, survival, in, 'Snca(-/-)', mice, was, comparable, to, 'controls,', the, levels, of, 'ROS', and, of, 'NOS-2', were, significantly]), verbo([decreased]), complemento([in, mature, erythrocytes, in, these, animals])]). relacion([sujeto(['These', results, indicate, a, role, for, 'α-synuclein', in]), verbo([regulating]), complemento([oxidative, stress, in, erythrocytes, in, vivo, and, could, open, new, avenues, for, the, investigation, of, its, function, in, 'non-neural', tissue])]). relacion([sujeto(['The', 'JAK2V617F', mutation, is]), verbo([found]), complemento([in, the, majority, of, patients, with, myeloproliferative, neoplasms, '(', 'MPNs)'])]). relacion([sujeto(['Transgenic', expression, of, the, mutant, gene]), verbo([causes]), complemento(['MPN-like', phenotypes, in, mice])]). relacion([sujeto(['We']), verbo([have]), complemento([produced, 'JAK2V617F', mice, with, p53, null, background])]). relacion([sujeto(['When', transplanted, into, 'C57Bl/6', 'mice,', 'J53Z1', cells]), verbo([induced]), complemento([acute, erythroleukemia, with, massive, infiltration, of, tumor, cells, in, the, spleen, and, liver])]). relacion([sujeto(['J53Z1', cells, were, responsive, to, stimulation, with, erythropoietin, and, stem, cell, factor, and, were, selectively]), verbo([inhibited]), complemento([by, 'JAK2', inhibitors, which, induced, apoptosis, of, the, cells])]). relacion([sujeto(['Together,', 'J53Z1', cells, belong, to, the, erythroid, 'lineage,', and, they, may, be, useful, for, studying, the, role, of, 'JAK2V617F', in, proliferation, and, differentiation, of, erythroid, cells, and, for, identifying, potential, therapeutic, drugs]), verbo([targeting]), complemento(['JAK2'])]). relacion([sujeto(['In', this, issue, of, 'Blood,', 'Gagne', et, al, describe, a, cohort, of, 362, patients, clinically, classified, as, having, 'Diamond-Blackfan', anemia, '(', 'DBA),', in, which, 175, '(', 48, '%', ')', were]), verbo([found]), complemento([to, have, mutations, and, deletions, in, ribosomal, protein, genes, or, 'GATA1,', and, 8, of, the, remaining, patients, '(', 2.2, '%', 'overall)', had, mitochondrial, gene, deletions, consistent, with, 'Pearson', 'marrow-pancreas', syndrome, '(', 'PS)'])]). relacion([sujeto(['Somatic', gene, mutations]), verbo([associated]), complemento([with, acute, leukemia, including, 'FLT3,', 'RAS', and, 'PTPN11', were, revisited])]). relacion([sujeto(['There', were, 42, cases, of, congenital, leukemia]), verbo([associated]), complemento([with, 'Down', syndrome, '(', 'DS)', and, 39, of, these, cases, presented, features, of, acute, myeloid, leukemia, '(', 'AML)-M7'])]). relacion([sujeto(['GATA1', mutations, were]), verbo([found]), complemento([in, 70, '%', of, these, cases])]). relacion([sujeto(['The', 'FLT3', mutation, was, not, 'found,', while, 'RAS', '(', n, =, 4, ')', and, 'PTPN11', '(', n, =, 2, ')', mutations, were, identified, and]), verbo([reported]), complemento([for, the, first, time, in, 'NL'])]). relacion([sujeto(['Emerging', evidence]), verbo([has]), complemento([shown, that, microRNAs, have, key, roles, in, regulating, various, normal, physiological, 'processes,', whereas, their, deregulated, expression, is, correlated, with, various, diseases])]). relacion([sujeto(['Recent', work, indicated, that, 'miR-146a']), verbo([has]), complemento([a, close, relationship, with, inflammation, and, autoimmune, diseases])]). relacion([sujeto(['miR-146-deficient', mice]), verbo([have]), complemento([developed, some, abnormal, hematopoietic, 'phenotypes,', suggesting, the, potential, functions, of, 'miR-146', in, hematopoietic, development])]). relacion([sujeto(['In', this, 'study,', we]), verbo([found]), complemento([that, 'miR-146b', was, consistently, 'up-regulated', in, both, 'K562', and, 'CD34(+)', hematopoietic, 'stem/progenitor', cells, '(', 'HSPCs)', undergoing, either, erythroid, or, megakaryocytic, differentiation])]). relacion([sujeto(['Remarkably,', erythroid, and, megakaryocytic, maturation, of, 'K562', cells, was]), verbo([induced]), complemento([by, excess, 'miR-146b', but, inhibited, by, decreased, 'miR-146b', levels])]). relacion([sujeto(['More', 'importantly,', an, mRNA, encoding, receptor, tyrosine, 'kinase,', namely, 'platelet-derived', growth, factor, receptor, α, '(', 'PDGFRA),', was, identified, and, validated, as, a, direct]), verbo([target]), complemento([of, 'miR-146b', in, hematopoietic, cells])]). relacion([sujeto(['miR-146b', could, ultimately, affect, the, expression, of, the, 'GATA-1', 'gene,', which, is]), verbo([regulated]), complemento([by, 'HEY1', '(', 'Hairy/enhancer-of-split', related, with, 'YRPW', motif, protein, 1, ')', ',', a, transcriptional, 'repressor,', via, inhibition, of, the, 'PDGFRA/JNK/JUN/HEY1', pathway])]). relacion([sujeto(['Lentivirus-mediated', gene, transfer, also, demonstrated, that, the, overexpression, of, 'miR-146b']), verbo([promoted]), complemento([erythropoiesis, and, megakaryocytopoiesis, of, 'HSPCs', via, its, regulation, on, the, 'PDGFRA', gene, and, effects, on, 'GATA-1', expression])]). relacion([sujeto(['Moreover,', we, confirmed, that, the]), verbo([binding]), complemento([of, 'GATA-1', to, the, 'miR-146b', promoter, and, induction, of, 'miR-146b', during, hematopoietic, maturation, were, dependent, on, 'GATA-1'])]). relacion([sujeto(['Therefore,', 'miR-146b,', 'PDGFRA,', and, 'GATA-1', formed, a, regulatory, circuit, to]), verbo([promote]), complemento([erythroid, and, megakaryocytic, differentiation])]). relacion([sujeto(['Previously,', we]), verbo([reported]), complemento([that, 'Runx1(+)', cells, in, embryonic, day, 7.5, '(', 'E7'])]). relacion([sujeto(['This']), verbo([suggests]), complemento([a, developmental, trajectory, from, 'Runx1(+)', cells, in, the, 'E7'])]). relacion([sujeto(['In', zebrafish, 'embryos,', it]), verbo([has]), complemento([been, suggested, that, primitive, neutrophils, may, originate, in, two, distinct, 'sites,', the, anterior, '(', 'ALPM)', and, posterior, lateral, plate, mesoderm, '(', 'PLPM)'])]). relacion([sujeto(['An', 'ETS-family', transcription, factor, 'Etsrp/Etv2/ER71']), verbo([has]), complemento([been, implicated, in, vasculogenesis, and, hematopoiesis, in, multiple, vertebrates])]). relacion([sujeto(['Here', we, demonstrate, using, zebrafish, embryos, that, 'Etv2']), verbo([has]), complemento([a, specific, 'cell-autonomous', function, during, primitive, neutropoiesis, in, the, anterior, lateral, plate, mesoderm, '(', 'ALPM)', but, has, little, effect, on, erythropoiesis, or, the, posterior, lateral, plate, mesoderm, '(', 'PLPM)', expression, of, neutrophil, marker, myeloperoxidase, 'mpo/mpx'])]). relacion([sujeto(['Yet,', how, mutations, in, genes, encoding, ubiquitously]), verbo([expressed]), complemento([proteins, such, as, these, result, in, 'cell-type-', and, 'tissue-specific', defects, remains, unknown])]). relacion([sujeto(['Here,', we, identify, mutations, in, 'GATA1,', encoding, the, critical, hematopoietic, transcription, factor, 'GATA-binding', 'protein-1,', that, reduce, levels, of, 'full-length', 'GATA1', protein, and]), verbo([cause]), complemento(['DBA', in, rare, instances])]). relacion([sujeto(['We', show, that, ribosomal, protein, 'haploinsufficiency,', the, more, common]), verbo([cause]), complemento([of, 'DBA,', can, lead, to, decreased, 'GATA1', mRNA, 'translation,', possibly, resulting, from, a, higher, threshold, for, initiation, of, translation, of, this, mRNA, in, comparison, with, other, mRNAs])]). relacion([sujeto(['In', primary, hematopoietic, cells, from, patients, with, mutations, in, 'RPS19,', encoding, ribosomal, protein, 'S19,', the, amplitude, of, a, transcriptional, signature, of, 'GATA1']), verbo([target]), complemento([genes, was, globally, and, specifically, 'reduced,', indicating, that, the, 'activity,', but, not, the, mRNA, 'level,', of, 'GATA1', is, decreased, in, patients, with, 'DBA', associated, with, mutations, affecting, ribosomal, proteins])]). relacion([sujeto(['Moreover,', the, defective, hematopoiesis, observed, in, patients, with, 'DBA']), verbo([associated]), complemento([with, ribosomal, protein, haploinsufficiency, could, be, partially, overcome, by, increasing, 'GATA1', protein, levels])]). relacion([sujeto(['Our', results]), verbo([provide]), complemento([a, paradigm, by, which, selective, defects, in, translation, due, to, mutations, affecting, ubiquitous, ribosomal, proteins, can, result, in, human, disease])]). relacion([sujeto(['Patients', with, physical, findings, suggestive, of, 'Treacher', 'Collins', syndrome, '(', 'TCS)', or, mandibulofacial, dysostosis, '(', 'MFD)', and, macrocytic, anemia, diagnostic, of, 'Diamond-Blackfan', anemia, '(', 'DBA)']), verbo([have]), complemento([been, reported])]). relacion([sujeto(['Disease-causing', genes]), verbo([have]), complemento([been, identified, for, 'TCS', and, other, 'MFDs'])]). relacion([sujeto(['However,', no, 'disease-causing', mutation, had, been, identified, in, the]), verbo([reported]), complemento([patients, with, the, combination, of, 'TCS/MFD', and, 'DBA', 'phenotype,', and, we, hypothesized, that, pathogenic, mutations, in, a, single, gene, could, be, identified, using, whole, exome, analysis])]). relacion([sujeto(['One', variant, was, predicted, to, affect, mRNA, 'splicing,', and, the, other, to]), verbo([lead]), complemento([to, protein, truncation])]). relacion([sujeto(['In', another, family, a, likely, pathogenic, 'X-linked', mutation, affecting, a, highly]), verbo([conserved]), complemento([residue, was, found, in, 'TSR2,', which, encodes, a, direct, binding, partner, of, 'RPS26'])]). relacion([sujeto(['De', novo, mutations, affecting, the, 'RPS28', start, codon, were]), verbo([found]), complemento([in, two, unrelated, 'probands,', identifying, 'RPS28', as, a, novel, disease, gene])]). relacion([sujeto(['Each', of, the, pathogenic, variants, identified, is, predicted, to, impede, ribosome, 'biogenesis,', which, in, turn, could, result, in, altered, cell, growth, and, 'proliferation,']), verbo([causing]), complemento([abnormal, embryologic, 'development,', defective, erythropoiesis, and, reduced, growth])]). relacion([sujeto(['This', clone]), verbo([leads]), complemento([to, a, full, malignant, tumor, through, additional, mutations, and, selection, processes])]). relacion([sujeto(['The', 'over-expression', of, 'GATA1', in, the, megakaryocytic, lineage, in, 'DS', fetal, liver, cells, is, proposed, to, be, the]), verbo([cause]), complemento([of, targeted, 'GATA1', somatic, mutations])]). relacion([sujeto(['C/EBPα', is]), verbo([expressed]), complemento([preferentially, in, myeloid, compared, with, lymphoid, or, erythroid, cells, and, directs, myeloid, lineage, specification])]). relacion([sujeto(['C/EBPα', is, also]), verbo([expressed]), complemento([at, lower, levels, in, 'HSCs', and, in, several, nonhematopoietic, tissues])]). relacion([sujeto(['The', 'Cebpa', gene]), verbo([has]), complemento([a, 'conserved,', 450, -, bp, segment, at, +, 37, kb, that, harbors, 'enhancer-specific', epigenetic, marks, and, is, activate, in, a, myeloid, cell, line])]). relacion([sujeto(['Herein,', we, characterize, transgenic, 'C57BL/6', 'mice,', in, which, the, 'Cebpa', enhancer, and, 845, -, bp, promoter]), verbo([regulate]), complemento([a, hCD4, reporter])]). relacion([sujeto(['FACS', 'analysis,', in, vitro, colony, 'assays,', and, in, vivo, competitive, and, secondary, transplantation, revealed, that, myeloid, but, not, 'MEPs', or, lymphoid, progenitors, and, also, functional, 'LT-HSCs', are]), verbo([found]), complemento([almost, exclusively, in, the, 'Cebpa-hCD4(+)', compared, with, 'hCD4(-)', marrow, population])]). relacion([sujeto([1, 'RNAs', were, preferentially]), verbo([expressed]), complemento([in, 'hCD4(+)', 'CMP,', 'Scl,', 'Gata2,', 'Gata1,', 'Klf1,', 'Ets1,', and, 'Fli1', predominated, in, 'hCD4(-)', 'CMP,', and, 'Runx1,', 'Myb,', 'HoxA9,', and, 'Erg', levels, were, similar, in, both])]). relacion([sujeto(['However,', a, limited, number, of, patients, with, 'TMD', but, without, 'Down', syndrome]), verbo([have]), complemento([been, 'reported,', all, with, a, blast, population, with, numeric, or, rarely, structural, chromosome, 21, abnormalities])]). relacion([sujeto(['This', case]), verbo([report]), complemento([suggests, that, unknown, disease, mechanisms, may, provoke, or, mimic, 'TMD'])]). relacion([sujeto(['This', case]), verbo([report]), complemento([is, followed, by, a, concise, review, of, the, literature, discussing, the, different, entities, and, pathomechanisms, of, 'TMD', and, acute, megakaryocytic, leukaemia, in, patients, with, or, without, 'Down', syndrome])]). relacion([sujeto(['The', directed, differentiation, toward, erythroid, '(', 'E)', or, megakaryocytic, '(', 'MK)', lineages, by, the, 'MK-E', progenitor, '(', 'MEP)', could]), verbo([enhance]), complemento([the, ex, vivo, generation, of, red, blood, cells, and, platelets, for, therapeutic, transfusions])]). relacion([sujeto(['Although', many, 'TFs']), verbo([have]), complemento([been, 'implicated,', 'E', or, 'MK', differentiation, is, a, complex, process, requiring, multiple, 'days,', and, the, dynamics, of, 'TF', activities, during, commitment, and, terminal, maturation, are, relatively, unexplored])]). relacion([sujeto(['Dynamic', 'TF', activity, profiles]), verbo([associated]), complemento([with, differentiation, towards, each, lineage, were, 'identified,', and, validated, with, previous, reports])]). relacion([sujeto(['From', these, activity, 'profiles,', we, show, that, 'GATA-1', is, an, important, hub, during, early, 'hemin-', and, 'PMA-induced', 'differentiation,', and]), verbo([reveal]), complemento([several, characteristic, 'TF', interactions, for, 'E', and, 'MK', differentiation, that, confirm, regulatory, mechanisms, documented, in, the, literature])]). relacion([sujeto(['Furthermore,', we, investigated, the, mechanism, by, which, nicotinamide, '(', 'NIC)']), verbo([promoted]), complemento([terminal, 'MK', maturation, using, an, 'MK-committed', cell, 'line,', 'CHRF-288-11', '(', 'CHRF)'])]). relacion([sujeto(['Concomitant', with, its, enhancement, of, 'ploidy,', 'NIC', strongly]), verbo([enhanced]), complemento([the, activity, of, three, 'TFs', with, known, involvement, in, terminal, 'MK', 'maturation:', 'FLI-1,', 'NF-E2,', and, p53])]). relacion([sujeto(['The', 'interferon-γ', '(', 'IFNγ)/signal', transducer, and, activator, of, transcription, 1, '(', 'Stat1)', pathway, shows, higher, activity, in, patients, with, essential, thrombocythemia, '(', 'ET)', than, in, polycythemia, vera, '(', 'PV)', and, was, proposed, to, be]), verbo([promoting]), complemento([the, 'ET', phenotype])]). relacion([sujeto(['We', explored, the, phenotypic, consequences, of, 'Stat1', deficiency, on, the, effects, of, 'Janus', kinase, 2, '(', 'JAK2)-V617F', in, vivo, by, crossing, mice]), verbo([expressing]), complemento(['JAK2-V617F', with, 'Stat1', knockout, mice])]). relacion([sujeto(['Bone', marrow, transplantation, reproduced, these, phenotypic, changes, in, 'wild-type', 'recipients,', demonstrating, that, the, effect, of, 'Stat1', is, 'cell-intrinsic', and, does, not]), verbo([require]), complemento([a, 'Stat1-deficient', microenvironment])]). relacion([sujeto(['Deletion', of, 'Stat1']), verbo([increased]), complemento(['burst-forming', 'unit-erythroid', and, reduced, 'colony-forming', 'unit-megakaryocyte', colony, formation, driven, by, 'JAK2-V617F,', but, was, not, sufficient, to, completely, normalize, the, platelet, count])]). relacion([sujeto(['Gata1,', a, key, regulator, of, megakaryopoiesis, and, 'erythropoiesis,', was]), verbo([decreased]), complemento([in, 'Stat1-deficient', platelets])]). relacion([sujeto(['Together,', these, results, support, the, concept, that]), verbo([activating]), complemento(['Stat1', in, the, presence, of, 'JAK2-V617F,', for, 'example,', through, 'IFNγ,', constrains, erythroid, differentiation, and, promotes, megakaryocytic, 'development,', resulting, in, 'ET', phenotype])]). relacion([sujeto(['Hematopoiesis', is, an, exquisitely]), verbo([regulated]), complemento([process, in, which, stem, cells, in, the, developing, embryo, and, the, adult, generate, progenitor, cells, that, give, rise, to, all, blood, lineages])]). relacion([sujeto(['Master', regulatory, transcription, factors, control, hematopoiesis, by, integrating, signals, from, the, microenvironment, and, dynamically, establishing, and]), verbo([maintaining]), complemento([genetic, networks])]). relacion([sujeto(['Transformative', technologic, advances]), verbo([involving]), complemento([the, coupling, of, 'next-generation', 'DNA', sequencing, technology, with, the, chromatin, immunoprecipitation, assay, '(', 'ChIP-seq)', have, enabled, 'genome-wide', mapping, of, factor, occupancy, patterns])]). relacion([sujeto(['It']), verbo([has]), complemento([become, en, vogue, to, map, transcription, factor, occupancy, patterns, 'genome-wide,', while, using, powerful, statistical, tools, to, establish, correlations, to, inform, biology, and, mechanisms])]). relacion([sujeto(['This', review, focuses, on, key, discoveries, that]), verbo([have]), complemento([emerged, during, the, path, from, single, loci, to, 'genome-wide', 'analyses,', specifically, in, the, context, of, hematopoietic, transcriptional, mechanisms])]). relacion([sujeto(['Growth', factor, independence, 1, b, '(', 'GFI1B)', is, a, 'DNA']), verbo([binding]), complemento([repressor, of, transcription, with, vital, functions, in, hematopoiesis])]). relacion([sujeto(['To', analyze, the, full, functionality, of, 'Gfi1b,', we, used, conditionally, deficient, mice, that, harbor, floxed, 'Gfi1b', alleles, and, inducible, '(', 'Mx-Cre,', 'Cre-ERT)', or, erythroid, specific, '(', 'EpoR-Cre)', 'Cre']), verbo([expressing]), complemento([transgenes])]). relacion([sujeto(['In', contrast, to, the, germline, 'knockout,', 'EpoR-Cre']), verbo([mediated]), complemento([erythroid, specific, ablation, of, 'Gfi1b', allows, full, 'gestation,', but, causes, perinatal, lethality, with, very, few, mice, surviving, to, adulthood])]). relacion([sujeto(['Both', the, embryonic, deletion, of, 'Gfi1b', by, 'EpoR-Cre', and, the, deletion, in, adult, mice, by, 'Mx-Cre', or, 'Cre-ERT']), verbo([leads]), complemento([to, reduced, numbers, of, erythroid, 'precursors,', perturbed, and, delayed, erythroid, 'maturation,', anemia, and, extramedullary, erythropoiesis])]). relacion([sujeto([and, an]), verbo([increased]), complemento([level, of, 'Hbb-bh1', and, 'Hbb-y', embryonic, globin, gene, expression, was, even, maintained, in, adult, 'Gfi1b', deficient, mice])]). relacion([sujeto(['While', the, expression, of, 'Bcl11a,', a, regulator, of, embryonic, globin, expression, was, not, affected, by, 'Gfi1b', 'deficiency,', the, expression, of, 'Gata1', was, reduced, and, the, expression, of, 'Sox6,', also]), verbo([involved]), complemento([in, globin, 'switch,', was, almost, entirely, lost, when, 'Gfi1b', was, absent])]). relacion([sujeto(['We']), verbo([report]), complemento([a, rare, case, of, transient, abnormal, myelopoiesis, '(', 'TAM)', in, a, phenotypically, normal, neonate])]). relacion([sujeto(['Further', analysis, identified, a, mutation, in, 'GATA1', along, with, the, unique]), verbo([finding]), complemento([of, two, different, trisomic, cell, 'lines,', detected, upon, 'karyotyping;', one, with, trisomy, 21, 'only,', and, one, with, trisomies, 21, and, 22, ',', which, was, present, in, a, subpopulation, of, peripheral, blood, cells])]). relacion([sujeto(['Abstract', 'Endothelial', progenitor, cells, '(', 'EPCs)']), verbo([have]), complemento([been, demonstrated, to, be, effective, for, the, treatment, of, cardiovascular, diseases])]). relacion([sujeto(['However,', the, differentiation, process, from, circulation, to, adhesion]), verbo([has]), complemento([not, been, clarified, because, circulating, 'EPCs', rarely, attached, to, dishes, in, 'EPC', cultures, previously])]). relacion([sujeto(['The', bioactivities, of, 'adhesion,', 'proliferation,', 'migration,', tube, 'formation,', and, differentiated, type, of, 'EPC', colony, formation]), verbo([increased]), complemento([in, 'EPCs', exposed, to, dextran])]). relacion([sujeto(['The', surface, protein, expression, rate, of, the, endothelial, markers, vascular, endothelial, growth, factor, '(', 'VEGF)-R1/2,', 'VE-cadherin,', 'Tie2,', 'ICAM1,', 'VCAM1,', and, integrin, 'αv/β3']), verbo([increased]), complemento([in, 'EPCs', exposed, to, dextran])]). relacion([sujeto(['The', mRNA, levels, of, 'VEGF-R1/2,', 'VE-cadherin,', 'Tie2,', endothelial, nitric, oxide, 'synthase,', 'MMP9,', and, 'VEGF']), verbo([increased]), complemento([in, 'EPCs', treated, with, dextran])]). relacion([sujeto(['Those', of, 'endothelium-related', transcription, factors, 'ID1/2,', 'FOXM1,', 'HEY1,', 'SMAD1,', 'FOSL1,', 'NFkB1,', 'NRF2,', 'HIF1A,', 'EPAS1']), verbo([increased]), complemento([in, 'dextran-treated', 'EPCs;', 'however,', those, of, 'hematopoietic-', and, 'antiangiogenic-related', transcription, factors, 'TAL1,', 'RUNX1,', 'c-MYB,', 'GATA1/2,', 'ERG,', 'FOXH1,', 'HHEX,', 'SMAD2/3', decreased, in, 'dextran-exposed', 'EPCs'])]). relacion([sujeto(['Inhibitor', analysis, showed, that, 'PI3K/Akt,', 'ERK1/2,', 'JNK,', and, p38, signal, transduction, pathways, are]), verbo([involved]), complemento([in, the, differentiation, in, response, to, dextran])]). relacion([sujeto(['In', 'conclusion,', dextran]), verbo([induces]), complemento([differentiation, of, circulating, 'EPCs', in, terms, of, 'adhesion,', 'migration,', 'proliferation,', and, vasculogenesis])]). relacion([sujeto(['The', differentiation, mechanism, in, response, to, dextran, is]), verbo([regulated]), complemento([by, multiple, signal, transductions, including, 'PI3K/Akt,', 'ERK1/2,', 'JNK,', and, p38])]). relacion([sujeto(['Trisomy', 21, alters, fetal, liver, hematopoiesis, 'and,', in, combination, with, somatic, globin, transcription, factor, 1, '(', 'GATA1)', 'mutations,']), verbo([leads]), complemento([to, development, of, transient, myeloproliferative, disease, in, newborns])]). relacion([sujeto(['However,', little, is, known, about, the, morphological, hematopoietic, changes]), verbo([caused]), complemento([by, trisomy, 21, in, the, 'fetus,', and, to, 'date,', the, exact, onset, of, 'GATA1', mutations, remains, uncertain])]). relacion([sujeto(['Our', results]), verbo([suggest]), complemento([that, 'GATA1', exon, 2, mutations, occur, late, in, trisomy, 21, fetal, hematopoiesis])]). relacion([sujeto(['However,', trisomy, 21, alone]), verbo([provides]), complemento([a, proliferative, stimulus, of, fetal, megakaryopoiesis, and, erythropoiesis])]). relacion([sujeto(['CD34-positive', precursor, cells, are, not]), verbo([increased]), complemento([in, trisomy, 21, fetal, livers])]). relacion([sujeto(['Erythroid', 'differentiation-associated', gene, '(', 'EDAG)']), verbo([has]), complemento([been, considered, to, be, a, transcriptional, regulator, that, controls, hematopoietic, cell, 'differentiation,', 'proliferation,', and, apoptosis])]). relacion([sujeto(['In', this, 'study,', we]), verbo([found]), complemento([that, 'EDAG', is, highly, expressed, in, 'CMPs', and, 'MEPs', and, upregulated, during, the, erythroid, differentiation, of, 'CD34(+)', cells, following, erythropoietin, '(', 'EPO)', treatment])]). relacion([sujeto(['Overexpression', of, 'EDAG']), verbo([induced]), complemento([erythroid, differentiation, of, 'CD34(+)', cells, in, vitro, and, in, vivo, using, immunodeficient, mice])]). relacion([sujeto(['Detailed', mechanistic, analysis]), verbo([suggested]), complemento([that, 'EDAG', forms, complex, with, 'GATA1', and, p300, and, increases, 'GATA1', acetylation, and, transcriptional, activity, by, facilitating, the, interaction, between, 'GATA1', and, p300])]). relacion([sujeto(['EDAG', deletion, mutants, lacking, the]), verbo([binding]), complemento([domain, with, 'GATA1', or, p300, failed, to, enhance, erythroid, 'differentiation,', suggesting, that, 'EDAG', regulates, erythroid, differentiation, partly, through, forming, 'EDAG/GATA1/p300', complex])]). relacion([sujeto(['Microarray', analysis]), verbo([suggested]), complemento([that, 'EDAG', knockdown, selectively, inhibits, 'GATA1-activated', target, genes])]). relacion([sujeto(['These', data]), verbo([provide]), complemento([novel, insights, into, 'EDAG', in, regulation, of, erythroid, differentiation])]). relacion([sujeto(['Pearson', marrow, pancreas, syndrome, '(', 'PS)', is, a, multisystem, disorder]), verbo([caused]), complemento([by, mitochondrial, 'DNA', '(', 'mtDNA)', deletions])]). relacion([sujeto(['Diamond-Blackfan', anemia, '(', 'DBA)', is, a, congenital, hypoproliferative, anemia, in, which, mutations, in, ribosomal, protein, genes, and, 'GATA1']), verbo([have]), complemento([been, implicated])]). relacion([sujeto(['Because', of, the, overlapping, features, and, relative, rarity, of, 'PS,', we, hypothesized, that, some, patients, in, whom, the]), verbo([leading]), complemento([clinical, diagnosis, is, 'DBA', actually, have, 'PS'])]). relacion([sujeto(['Here,', we, evaluated, patient, 'DNA', samples, submitted, for, 'DBA', genetic, studies, and]), verbo([found]), complemento([that, 8, '(', 4.6, '%', ')', of, 173, genetically, uncharacterized, patients, contained, large, mtDNA, deletions])]). relacion([sujeto(['Anemia', ranges, from, minimal, '(', mild, 'dyserythropoiesis)', to, severe, '(', hydrops, fetalis]), verbo([requiring]), complemento([in, utero, 'transfusion)'])]). relacion([sujeto(['At', the, extreme, end, of, the, clinical, 'spectrum,', severe, hemorrhage, 'and/or', erythrocyte, transfusion, dependence, are, life, 'long;', at, the, milder, 'end,', anemia, and, the, risk, for, bleeding]), verbo([decrease]), complemento([spontaneously, with, age])]). relacion([sujeto(['Female', carriers, may]), verbo([have]), complemento([mild, to, moderate, 'symptoms,', such, as, menorrhagia])]). relacion([sujeto(['In', some, cases, electron, microscopy]), verbo([reveals]), complemento([reduced, numbers, of, platelet, alpha, granules, and, dysplastic, features, in, platelets, and, megakaryocytes])]). relacion([sujeto(['GATA1', is, the, only, gene, in, which, pathogenic, variants, are, known, to]), verbo([cause]), complemento(['GATA1-related', cytopenia])]). relacion([sujeto(['Evaluation', of, relatives, at, 'risk:', 'If', a, 'GATA1', pathogenic, variant]), verbo([has]), complemento([been, identified, in, the, 'family,', complete, blood, counts, and, molecular, genetic, testing, of, 'at-risk', relatives, can, be, offered])]). relacion([sujeto(['At-risk', relatives, who, choose, not, to]), verbo([have]), complemento([molecular, genetic, testing, should, have, complete, blood, counts, to, evaluate, for, 'thrombocytopenia,', 'anemia,', or, neutropenia])]). relacion([sujeto(['If', the, mother, of, an, affected, male]), verbo([has]), complemento([a, 'GATA1', pathogenic, 'variant,', the, chance, of, transmitting, it, in, each, pregnancy, is, 50, '%'])]). relacion([sujeto(['Carrier', testing, for, 'at-risk', family, members, and, prenatal, testing, for, pregnancies, at]), verbo([increased]), complemento([risk, are, possible, once, the, pathogenic, variant, has, been, identified, in, the, family])]). relacion([sujeto(['Protein', tyrosine, phosphatases, '(', 'PTPs)', are]), verbo([involved]), complemento([in, 'hematopoiesis,', but, the, function, of, many, 'PTPs', is, not, well, characterized, in, vivo])]). relacion([sujeto(['Here,', we]), verbo([have]), complemento([identified, 'Ptpn9a,', an, ortholog, of, human, 'PTPN9,', as, a, crucial, regulator, of, erythroid, cell, development, in, zebrafish, embryos])]). relacion([sujeto(['ptpn9a,', but, not, 'ptpn9b,', was]), verbo([expressed]), complemento([in, the, posterior, lateral, plate, mesoderm, and, intermediate, cell, mass, -, two, primitive, hematopoietic, sites, during, zebrafish, embryogenesis])]). relacion([sujeto(['Morpholino-mediated', knockdown, of, ptpn9a]), verbo([caused]), complemento([erythrocytes, to, be, depleted, by, inhibiting, erythroid, cell, maturation, without, affecting, erythroid, proliferation, and, apoptosis])]). relacion([sujeto(['Consistently,', both, 'dominant-negative', 'PTPN9', '(', with, mutation, 'C515S)', and, siRNA, against, 'PTPN9']), verbo([inhibited]), complemento([erythroid, differentiation, in, human, 'K562', cells])]). relacion([sujeto(['Mechanistically,', depletion, of, ptpn9, in, zebrafish, embryos, in, vivo, or, in, 'K562', cells, in, vitro]), verbo([increased]), complemento([phosphorylated, 'STAT3,', and, the, 'hyper-phosphorylated', 'STAT3', entrapped, and, prevented, the, transcription, factors, 'GATA1', and, 'ZBP-89', '(', also, known, as, 'ZNF148)', from, regulating, erythroid, gene, expression])]). relacion([sujeto(['These', findings, imply, that, 'PTPN9', plays, an, important, role, in, erythropoiesis, by, disrupting, an, inhibitory, complex, of]), verbo([phosphorylated]), complemento(['STAT3,', 'GATA1', and, 'ZBP-89,', providing, new, cellular, and, molecular, insights, into, the, role, of, ptpn9a, in, developmental, hematopoiesis])]). relacion([sujeto(['For', 'example,', we, recently]), verbo([found]), complemento([that, 'CD86(-)', 'CD150(+)', 'CD48(-)', 'HSCs', have, limited, potential, for, lymphocyte, production])]). relacion([sujeto(['Here,', we, analyzed, 'HSC', subsets, with, a, series, of, stem, cell, markers, in, 'JAK2V617F', transgenic, '(', 'Tg)', 'mice,', where, the, mutation, is, sufficient, to]), verbo([cause]), complemento([myeloproliferative, neoplasia, with, lymphocyte, deficiency])]). relacion([sujeto(['Careful', analysis]), verbo([suggested]), complemento([the, accumulation, involved, multiple, 'HSC', 'subsets,', but, particularly, those, characterized, as, 'CD150(HI)', 'CD86(-)', 'CD18(L)°CD41(+)', and, excluding, 'Hoechst', dye])]). relacion([sujeto(['Real-Time', 'PCR', analysis, of, their, 'HSC', revealed, that, the, erythropoiesis]), verbo([associated]), complemento([gene, transcripts, 'Gata1,', 'Klf1', and, 'Epor', were, particularly, high])]). relacion([sujeto(['Flow', cytometry, analyses, based, on, two, differentiation, schemes, for, multipotent, progenitors, '(', 'MPP)', also]), verbo([suggested]), complemento([alteration, by, 'JAK2', signals])]). relacion([sujeto(['The', low, 'CD86', on, 'HSC', and, multipotent, progenitors, paralleled, the, large, reductions, we]), verbo([found]), complemento([in, lymphoid, 'progenitors,', but, the, few, that, were, produced, functioned, normally, when, sorted, and, placed, in, culture])]). relacion([sujeto(['Either', of, two, 'HSC', subsets]), verbo([conferred]), complemento([disease, when, transplanted])]). relacion([sujeto(['As', with, the, other, rare, inherited, bone, marrow, failure, 'syndromes,', the, study, of, these, disorders]), verbo([provides]), complemento([important, insights, into, basic, biology, 'and,', in, the, case, of, 'DBA,', ribosome, 'biology;', the, disruption, of, which, characterizes, the, disorder])]). relacion([sujeto(['Thus', 'DBA', serves, as, a, paradigm, for, translational, medicine, in, which, the, efforts, of, clinicians, to, manage, 'DBA']), verbo([have]), complemento([informed, laboratory, scientists, 'who,', in, 'turn,', have, stimulated, clinical, researchers, to, utilize, scientific, discovery, to, provide, improved, care])]). relacion([sujeto(['In', this, review, we, describe, the, clinical, syndrome, 'Diamond', 'Blackfan', anemia, 'and,', in, 'particular,', we, demonstrate, how, the, study, of, 'DBA']), verbo([has]), complemento([allowed, scientific, inquiry, to, create, opportunities, for, progress, in, its, understanding, and, treatment])]). relacion([sujeto(['Most', heritable, anemias, are]), verbo([caused]), complemento([by, mutations, in, genes, encoding, 'globins,', red, blood, cell, '(', 'RBC)', membrane, 'proteins,', or, enzymes, in, the, glycolytic, and, hexose, monophosphate, shunt, pathways])]). relacion([sujeto(['A', less, common, class, of, genetic, anemia, is]), verbo([caused]), complemento([by, mutations, that, alter, the, functions, of, erythroid, transcription, factors, '(', 'TFs)'])]). relacion([sujeto(['Many', 'TF', mutations]), verbo([associated]), complemento([with, heritable, anemia, cause, truncations, or, amino, acid, 'substitutions,', resulting, in, the, production, of, functionally, altered, proteins])]). relacion([sujeto(['Characterization', of, these, mutant, proteins]), verbo([has]), complemento([provided, insights, into, mechanisms, of, gene, 'expression,', hematopoietic, 'development,', and, human, disease])]). relacion([sujeto(['Mutations', within, promoter, or, enhancer, regions, that, disrupt, 'TF']), verbo([binding]), complemento([to, essential, erythroid, genes, also, cause, anemia, and, heritable, variations, in, 'RBC', 'traits,', such, as, fetal, hemoglobin, content])]). relacion([sujeto(['Defining', the, latter, may]), verbo([have]), complemento([important, clinical, implications, for, 'de-repressing', fetal, hemoglobin, synthesis, to, treat, sickle, cell, anemia, and, β, thalassemia])]). relacion([sujeto(['Findings', obtained, through, such, studies, of, 'RBCs', and]), verbo([associated]), complemento([diseases, are, likely, generalizable, to, many, human, diseases, and, quantitative, traits])]). relacion([sujeto([1, ',', 'GATA1,', and, 'GATA2', into, the, human, mast, cell, 'line,', 'LAD2,']), verbo([caused]), complemento([significant, downregulation, of, cell, surface, expression, of, 'FcεRI'])]). relacion([sujeto([1, ',', 'GATA1,', and, 'GATA2', siRNAs]), verbo([suppressed]), complemento([the, α, 'transcript,', whereas, the, amount, of, β, mRNA, was, reduced, in, only, 'GATA2', siRNA, transfectants])]). relacion([sujeto([1, ',', 'GATA1,', and, 'GATA2']), verbo([bind]), complemento([to, the, promoter, region, of, 'FCER1A', '(', encoding, 'FcεRIα)', and, that, 'GATA2', binds, to, the, promoter, of, 'MS4A2', '(', encoding, 'FcεRIβ)'])]). relacion([sujeto(['These', knockdowns, of, transcription, factors, also]), verbo([suppressed]), complemento([the, 'IgE-mediated', degranulation, activity, of, 'LAD2'])]). relacion([sujeto(['Similarly,', all, three, knockdowns]), verbo([suppressed]), complemento(['FcεRI', expression, in, primary, mast, 'cells,', especially, 'PU'])]). relacion([sujeto([1, siRNA, and, 'GATA2', 'siRNA,', which]), verbo([target]), complemento(['FcεRIα', and, 'FcεRIβ,', respectively])]). relacion([sujeto([1, and, 'GATA1', are]), verbo([involved]), complemento([in, 'FcεRIα', transcription, through, recruitment, to, its, 'promoter,', whereas, 'GATA2', positively, regulates, 'FcεRIβ', transcription])]). relacion([sujeto(['Suppression', of, these, transcription, factors]), verbo([leads]), complemento([to, downregulation, of, 'FcεRI', expression, and, 'IgE-mediated', degranulation, activity])]). relacion([sujeto(['GATA1', is, indispensable, for, survival, and, terminal, differentiation, of, 'erythroid,', megakaryocytic, and, eosinophilic, 'progenitors,', whereas, 'GATA2']), verbo([regulates]), complemento([proliferation, and, maintenance, of, hematopoietic, stem, and, progenitor, cells])]). relacion([sujeto(['Expression', levels, of, 'GATA1', and, 'GATA2', are, primarily]), verbo([regulated]), complemento([at, the, transcriptional, level, through, 'auto-', and, reciprocal, regulatory, networks, formed, by, these, 'GATA', factors])]). relacion([sujeto(['The', dynamic, and, strictly, controlled, change, of, expression, from, 'GATA2', to, 'GATA1', during, erythropoiesis]), verbo([has]), complemento([been, referred, to, as, 'GATA', factor, 'switching,', which, plays, a, crucial, role, in, erythropoiesis])]). relacion([sujeto(['The', regulatory, network, comprising, 'GATA1', and, 'GATA2', gives, rise, to, the, 'stage-specific', changes, in, 'Gata1', and, 'Gata2', gene, expression, during, erythroid, 'differentiation,', which]), verbo([ensures]), complemento([specific, expression, of, early, and, late, erythroid, genes, at, each, stage])]). relacion([sujeto(['Recent', studies]), verbo([have]), complemento([also, shed, light, on, the, 'genome-wide', binding, profiles, of, 'GATA1', and, 'GATA2,', and, the, significance, of, epigenetic, modification, of, 'Gata1', gene, during, erythroid, differentiation])]). relacion([sujeto(['Some', 'Kampo', medicines, that, are, herbal, and, traditional, in, 'Japan']), verbo([have]), complemento([had, beneficial, effects, when, given, to, patients, with, anemia])]). relacion([sujeto(['Among', 'them,', 'NYT', was, most, effective, in]), verbo([stimulating]), complemento([cell, proliferation, and, 'up-regulating', 'Myc', expression])]). relacion([sujeto(['Flow', cytometry, analysis, indicated, 'that,', among, hematopoietic, components, of, those, 'cultures,', myeloid, cells]), verbo([expressing]), complemento(['CD45/Mac-1/Gr-1/F4/80', increased, in, 'number,', but, 'Ter119/CD71', erythroid, cells, did, not])]). relacion([sujeto(['Overall,', these, findings]), verbo([provide]), complemento([molecular, evidence, that, 'NYT', accelerates, myelopoiesis, but, not, erythropoiesis, in, vitro])]). relacion([sujeto(['Although', previous, studies]), verbo([have]), complemento([shown, that, 'GATA1', is, required, for, mast, cell, 'differentiation,', the, effects, of, the, complete, ablation, of, 'GATA1', in, mast, cells, have, not, been, examined])]). relacion([sujeto(['Using', conditional, 'Gata1', knockout, mice, '(', 'Gata1(-/y)),', we, demonstrate, here, that, the, complete, ablation, of, 'GATA1']), verbo([has]), complemento([a, minimal, effect, on, the, number, and, distribution, of, peripheral, tissue, mast, cells, in, adult, mice])]). relacion([sujeto(['Microarray', analyses, showed, that, the, repression, of, 'GATA1', in, bone, marrow, mast, cells, '(', 'BMMCs)']), verbo([has]), complemento([a, small, impact, on, the, mast, 'cell-specific', gene, expression, in, most, cases])]). relacion([sujeto([3, were, uniformly, reduced, in, the, 'GATA1', knockdown, 'cells,', and, 'GATA1', was]), verbo([found]), complemento([to, bind, to, a, 500, -, bp, region, at, the, 5, '\'', end, of, this, locus])]). relacion([sujeto(['Revealing', a, sharp, contrast, to, that, observed, in, the, 'Gata1-null', 'BMMCs,', 'GATA2', deficiency, resulted, in, a, significant]), verbo([loss]), complemento([of, the, 'c-Kit(+)', 'FcεRIα(+)', mast, cell, fraction, and, a, reduced, expression, of, several, mast, 'cell-specific', genes])]). relacion([sujeto(['Although', studies]), verbo([have]), complemento([identified, several, miRNAs, that, regulate, erythroid, commitment, and, 'differentiation,', we, do, not, understand, the, mechanism, by, which, the, crucial, erythroid, transcription, 'factors,', 'GATA-1and', 'NF-E2', directly, regulate, and, control, differentiation, via, miRNA, pathways])]). relacion([sujeto(['Furthermore,', the]), verbo([increase]), complemento([of, 'miR-199b-5p', in, erythroid, cells, occurred, in, a, 'GATA-1-', and, 'NF-E2-dependent', manner, during, erythrocyte, maturation])]). relacion([sujeto(['Both', 'GATA-1', and, 'NF-E2']), verbo([bound]), complemento([upstream, of, the, 'miR-199b', gene, locus, and, activated, its, transcription])]). relacion([sujeto(['Moreover,', we, identified, 'c-Kit', as, a, direct]), verbo([target]), complemento([of, 'miR-199b-5p', in, erythroid, cells])]). relacion([sujeto(['Taken', 'together,', our, results, establish, a, functional, link, among, the, erythroid, transcription, factors, 'GATA-1/NF-E2,', 'miR-199b-5p', and, 'c-Kit,', and]), verbo([provide]), complemento([new, insights, into, the, coupling, of, transcription, and, 'post-transcription', regulation, in, erythroid, differentiation])]). relacion([sujeto(['Key', transcriptional, regulators, of, terminal, 'erythropoiesis,', such, as, 'GATA-binding', factor, 1, '(', 'GATA1)', and, 'T-cell', acute, lymphocytic, leukemia, protein, 1, '(', 'TAL1),']), verbo([have]), complemento([been, well, 'characterized,', but, transcription, factors, and, cofactors, and, their, expression, modulations, have, not, yet, been, explored, on, a, global, scale])]). relacion([sujeto(['Here,', we, use, global, gene, expression, analysis, to, identify, 28, transcription, factors, and, 19, transcriptional, cofactors]), verbo([induced]), complemento([during, terminal, erythroid, differentiation, whose, promoters, are, enriched, for, binding, by, 'GATA1', and, 'TAL1'])]). relacion([sujeto(['TFDP2', is, a, critical, cofactor]), verbo([required]), complemento([for, proper, cell, cycle, control, and, gene, expression])]). relacion([sujeto(['GATA1', and, 'TAL1', are]), verbo([bound]), complemento([to, the, regulatory, regions, of, 'Tfdp2', and, upregulate, its, expression, and, knockdown, of, 'Tfdp2', results, in, significantly, reduced, rates, of, proliferation, as, well, as, reduced, upregulation, of, many, 'erythroid-important', genes])]). relacion([sujeto(['Loss', of, 'Tfdp2', also, globally]), verbo([inhibits]), complemento([the, normal, downregulation, of, many, 'E2F2', target, 'genes,', including, those, that, regulate, the, cell, 'cycle,', causing, cells, to, accumulate, in, 'S', phase, and, resulting, in, increased, erythrocyte, size])]). relacion([sujeto(['By', 'contrast,', 'HDAC4', content, drastically]), verbo([decreased]), complemento([and, 'HDAC5', remained, constant, in, content, but, decreased, in, activity])]). relacion([sujeto(['Treatment', of, erythroleukemic, cells, with, inhibitors, of, 'ERK', phosphorylation, reduced, by, &, 'gt;90%', the, total, and]), verbo([nuclear]), complemento([content, of, 'HDAC5,', 'GATA1', and, 'EKLF,', suggesting, that, 'ERK', phosphorylation, is, required, for, the, formation, of, this, complex])]). relacion([sujeto(['Based', on, the, function, of, class, 'IIa', 'HDACs', as, chaperones, of, other, proteins, to, the, nucleus, and, the, 'erythroid-specificity', of, 'HDAC5', 'localization,', this, novel, 'HDAC', complex, was, named]), verbo([nuclear]), complemento([remodeling, shuttle, erythroid, '(', 'NuRSERY)'])]). relacion([sujeto(['Exposure', of, erythroid, cells, to, the, class, 'II-selective', 'HDAC', inhibitor, '(', 'HDACi)', 'APHA9']), verbo([increased]), complemento(['γ/(γ+β)', globin, expression, ratios, '(', 'Mai', et, al])]). relacion([sujeto([',', 2007, ')', ',']), verbo([suggesting]), complemento([that, 'NuRSERY', may, regulate, globin, gene, expression])]). relacion([sujeto(['Since', exposure, to, 'APHA9', did, not, affect, survival, rates, or, p21, 'activation,', 'NuRSERY', may, represent, a, 'novel,', possibly, less, 'toxic,']), verbo([target]), complemento([for, epigenetic, therapies, of, hemoglobinopaties, and, other, disorders])]). relacion([sujeto(['We', propose, a, 'two-step', workflow, based, on, linear, model, to, investigate, the, significant, differences, between, 'MCF7', and, 'OHT', cells]), verbo([stimulated]), complemento([by, 17, 'β-estradiol', '(', 'E2)', respect, to, regulatory, transcription, factors, '(', 'TFs)', and, their, interactions])]). relacion([sujeto(['We', additionally, compared, predicted, regulatory, 'TFs', based, on, 'RNA', polymerase, 'II', '(', 'PolII)']), verbo([binding]), complemento([quantity, data, and, gene, expression, 'data,', which, were, taken, from, 'MCF7/MCF7+E2', and, 'OHT/OHT+E2', cell, lines, following, the, same, analysis, workflow])]). relacion([sujeto(['The', results, showed, 'PolII', data, could]), verbo([provide]), complemento([more, information, and, predict, more, recognizably, important, regulatory, 'TFs'])]). relacion([sujeto(['Large', differences, in, 'TF', regulatory, mode, were]), verbo([found]), complemento([between, two, cell, lines])]). relacion([sujeto(['Through', verified, through, 'GO', 'annotation,', enrichment, analysis, and, related, literature, regarding, these, 'TFs,', we]), verbo([found]), complemento([some, regulatory, 'TFs', such, as, 'AP-1,', 'C/EBP,', 'FoxA1,', 'GATA1,', 'Oct-1', and, 'NF-κB,', maintained, 'OHT', cells, through, molecular, interactions, or, signaling, pathways, that, were, different, from, the, surviving, 'MCF7', cells])]). relacion([sujeto(['Notably,', we]), verbo([found]), complemento([the, regulatory, patterns, of, different, motifs, of, the, same, 'TF', were, very, different, from, one, another, sometimes])]). relacion([sujeto(['The', 'TFs', that, were]), verbo([involved]), complemento([in, both, 'protein-protein', interactions, and, signaling, pathways, could, be, one, of, the, key, resistant, mechanisms, of, endocrine, therapy, and, thus, also, could, be, new, treatment, targets, for, endocrine, resistance])]). relacion([sujeto(['First,', 'MRHMMs']), verbo([provides]), complemento([a, diverse, set, of, emission, probability, 'structures,', including, mixture, of, multivariate, normal, distributions, and, '(', 'logistic)', regression, models])]). relacion([sujeto(['net/projects/mrhmms/', 'Previous', studies]), verbo([have]), complemento([shown, that, 'ZBP-89', '(', 'Zfp148)', plays, a, critical, role, in, erythroid, lineage, 'development,', with, its, loss, at, the, embryonic, stage, causing, lethal, anemia, and, thrombocytopenia])]). relacion([sujeto(['Its', role, in, adult, hematopoiesis]), verbo([has]), complemento([not, been, described])]). relacion([sujeto(['We', now, show, that, conditional, deletion, of, 'ZBP-89', in, adult, mouse, hematopoietic, 'stem/progenitor', cells, '(', 'HSPC)']), verbo([causes]), complemento([anemia, and, thrombocytopenia, that, are, transient, in, the, steady, 'state,', but, readily, uncovered, following, chemically, induced, 'erythro/megakaryopoietic', stress])]). relacion([sujeto(['Unexpectedly,', stress]), verbo([induced]), complemento([by, bone, marrow, transplantation, of, 'ZBP89(-/-)', 'HSPC', also, resulted, in, a, 'myeloid-to-B', lymphoid, lineage, switch, in, bone, marrow, recipients])]). relacion([sujeto(['The', erythroid, and, 'myeloid/B', lymphoid, lineage, anomalies, in, 'ZBP89(-/-)', 'HSPC', are, reproduced, in, vitro, in, the, 'ZBP-89-silenced', multipotent, hematopoietic, cell, line, 'FDCP-Mix', 'A4,', and, are]), verbo([associated]), complemento([with, the, upregulation, of, 'PU'])]). relacion([sujeto(['These', data, identify, an, important, role, for, 'ZBP-89', in]), verbo([regulating]), complemento([stress, hematopoiesis, in, adult, mouse, bone, marrow])]). relacion([sujeto(['Mammals']), verbo([express]), complemento([thousands, of, long, noncoding, '(', 'lnc)', 'RNAs,', a, few, of, which, are, known, to, function, in, tissue, development])]). relacion([sujeto(['We', used, 'RNA', sequencing, to, identify, 1109, polyadenylated, lncRNAs]), verbo([expressed]), complemento([in, 'erythroblasts,', 'megakaryocytes,', and, 'megakaryocyte-erythroid', precursors, of, 'mice,', and, 594, in, erythroblasts, of, humans])]). relacion([sujeto(['Analysis', of, the, mouse, 'erythro-megakaryocytic', polyadenylated, lncRNA, transcriptome, indicates, that, '~75%', arise, from, promoters, and, 25, '%', from, 'enhancers,', many, of, which, are]), verbo([regulated]), complemento([by, key, transcription, factors, including, 'GATA1', and, 'TAL1'])]). relacion([sujeto(['Erythroid', lncRNA, expression, is, largely]), verbo([conserved]), complemento([among, 8, different, mouse, 'strains,', yet, only, 15, '%', of, mouse, lncRNAs, are, expressed, in, humans, and, vice, 'versa,', reflecting, dramatic, 'species-specificity'])]). relacion([sujeto(['RNA', interference, assays, of, 21, abundant, 'erythroid-specific', murine, lncRNAs, in, primary, mouse, erythroid, precursors, identified, 7, whose, knockdown]), verbo([inhibited]), complemento([terminal, erythroid, maturation])]). relacion([sujeto(['At', least, 6, of, these, 7, functional, lncRNAs]), verbo([have]), complemento([no, detectable, expression, in, human, 'erythroblasts,', suggesting, that, lack, of, conservation, between, mammalian, species, does, not, predict, lack, of, function])]). relacion([sujeto(['The', neutropenia]), verbo([caused]), complemento([by, 'TR', depletion, is, independent, of, telomere, length, and, telomerase, activity])]). relacion([sujeto(['Genetic', analysis, shows, that, 'TR']), verbo([modulates]), complemento([the, 'myeloid-erythroid', fate, decision, by, controlling, the, levels, of, the, master, myeloid, and, erythroid, transcription, factors, spi1, and, 'gata1,', respectively])]). relacion([sujeto(['Our', model, of, 'TR', deficiency, in, the, zebrafish, illuminates, the, 'non-canonical', roles, of, 'TR,', and, could, establish, therapeutic]), verbo([targets]), complemento([for, 'DC'])]). relacion([sujeto(['However,', recent, studies, indicate, that, 'EPO']), verbo([regulates]), complemento([multiple, aspects, of, terminal, maturation, of, primitive, murine, and, human, erythroid, 'precursors,', including, cell, 'survival,', 'proliferation,', and, the, rate, of, terminal, maturation])]). relacion([sujeto(['Flow', 'cytometry-based', 'methodologies,', developed, to, purify, murine, and, human, 'stage-specific', erythroid, 'precursors,']), verbo([have]), complemento([enabled, comparative, global, gene, expression, studies, and, are, providing, new, insights, into, the, biology, of, erythroid, maturation])]). relacion([sujeto(['TAL1', is, a, key, hematopoietic, transcription, factor, that]), verbo([binds]), complemento([to, regulatory, regions, of, a, large, cohort, of, erythroid, genes, as, part, of, a, complex, with, 'GATA-1,', 'LMO2', and, 'Ldb1'])]). relacion([sujeto(['The', complex]), verbo([mediates]), complemento(['long-range', interaction, between, the, 'β-globin', locus, control, region, '(', 'LCR)', and, active, globin, 'genes,', and, although, 'TAL1', is, one, of, the, two, 'DNA-binding', complex, 'members,', its, role, is, unclear])]). relacion([sujeto(['In', the, 'TAL1', knockdown, 'cells,', the, 'γ-globin', transcription, was, reduced, to, 35, '%', and, chromatin, looping, of, the, '(', 'G)γ-globin', gene, with, the, 'LCR', was, disrupted, with]), verbo([decreased]), complemento([occupancy, of, the, complex, member, 'Ldb1', and, 'LMO2', in, the, locus])]). relacion([sujeto(['However,', 'GATA-1', 'binding,', 'DNase', 'I', hypersensitive, site, formation, and, several, histone, modifications, were, largely]), verbo([maintained]), complemento([across, the, 'β-globin', locus])]). relacion([sujeto(['In', 'addition,', overexpression, of, 'TAL1']), verbo([increased]), complemento([the, 'γ-globin', transcription, and, increased, interaction, frequency, between, the, '(', 'G)γ-globin', gene, and, 'LCR'])]). relacion([sujeto(['In', this, issue, of, 'Blood,', 'Alvarez-Dominguez', et, al, use, a, combination, of, genomics, 'technology,', 'bioinformatics,', and, functional, analyses, to]), verbo([provide]), complemento([new, insights, into, our, understanding, of, the, role, of, long, noncoding, 'RNAs', '(', 'lncRNAs)', in, erythropoiesis])]). relacion([sujeto([lncRNAs]), verbo([have]), complemento([recently, emerged, as, 'critical,', multifunctional, regulators, of, cellular, gene, expression])]). relacion([sujeto(['Mutations', in, exon, 2, interfere, with, the, synthesis, of, the, 'full-length', isoform, of, 'GATA-1', and]), verbo([lead]), complemento([to, the, production, of, a, shortened, 'isoform,', 'GATA-1s'])]). relacion([sujeto(['These', mutations]), verbo([have]), complemento([been, found, in, patients, with, 'Diamond-Blackfan', anemia, '(', 'DBA),', a, congenital, erythroid, aplasia, typically, caused, by, mutations, in, genes, encoding, ribosomal, proteins])]). relacion([sujeto([2, 'T', &, 'gt;', 'C', mutation, in, the, initiation, codon]), verbo([leading]), complemento([to, the, loss, of, the, 'full-length', 'GATA-1', isoform])]). relacion([sujeto(['It', is, a, process, tightly]), verbo([regulated]), complemento([by, many, intrinsic, and, extrinsic, 'factors,', including, transcriptional, factors, and, signaling, molecules])]). relacion([sujeto(['Here', we, show, that, 'miR-144']), verbo([regulates]), complemento([hematopoiesis, and, vascular, development, in, zebrafish])]). relacion([sujeto(['Overexpression', of, 'miR-144']), verbo([inhibited]), complemento([primitive, hematopoiesis, as, demonstrated, by, a, reduced, number, of, circulating, blood, 'cells,', reduced, 'o-dianisidine', staining, of, 'hemoglobin,', and, reduced, expression, of, 'hbαe1,', 'hbβe1,', gata1, and, pu])]). relacion([sujeto(['Overexpression', of, 'miR-144', also]), verbo([inhibited]), complemento([definitive, hematopoiesis, as, shown, by, reduced, expression, of, runx1, and, 'c-myb'])]). relacion([sujeto(['Mechanistically,', 'miR-144']), verbo([regulates]), complemento([hematopoiesis, by, repressing, expression, of, meis1, involved, in, hematopoiesis])]). relacion([sujeto(['Bioinformatic', analysis, predicts, a]), verbo([target]), complemento([binding, sequence, for, 'miR-144', at, the, 3, '\'', -, 'UTR', of, meis1])]). relacion([sujeto(['Deletion', of, the, 'miR-144']), verbo([target]), complemento([sequence, eliminated, the, repression, of, meis1, expression, mediated, by, 'miR-144'])]). relacion([sujeto(['Finally,', because, meis1, is]), verbo([involved]), complemento([in, vascular, 'development,', we, tested, the, effect, of, 'miR-144', on, vascular, development])]). relacion([sujeto(['These', findings, establish, 'miR-144', as, a, novel, miRNA, that]), verbo([regulates]), complemento([hematopoiesis, and, vascular, development, by, repressing, expression, of, meis1])]). relacion([sujeto(['Studies', implicate, a, potential, role, for, 'EAF1', in, 'MLL-ELL']), verbo([induced]), complemento(['leukemogenesis;', however, the, biological, function, of, 'EAF1', in, this, process, remains, unknown])]). relacion([sujeto(['In', this, 'study,', we, show, that, knockdown, of, zebrafish, eaf1, by, morpholinos]), verbo([caused]), complemento([serious, defects, in, both, primitive, and, definitive, hematopoiesis])]). relacion([sujeto(['Using', microarray, 'analysis,', we, identified, foxo3b, as, a]), verbo([target]), complemento([gene, suppressed, by, eaf1])]). relacion([sujeto(['Ectopic', expression, of, foxo3b, in, embryos, mimicked, the, phenotypes, exhibited, in, eaf1, 'morphants,', except, that, foxo3b, had, no, effect, on, runx1, and, 'c-myb', expression, while, eaf1, morphants, did, not]), verbo([express]), complemento([these, markers, in, the, ventral, wall, of, dorsal, aorta])]). relacion([sujeto(['Subsequent', experiments, showed, that, a, dominant, negative, form, of, 'Foxo3b', '(', 'dn-foxo3b)', partially, restored, primitive, hematopoietic, defects, in, eaf1, 'morphants,']), verbo([suggesting]), complemento([that, foxo3b, might, serve, as, a, key, factor, for, mediating, eaf1, function, in, primitive, hematopoiesis])]). relacion([sujeto(['Furthermore,', we, observed, that, foxo3b]), verbo([inhibited]), complemento([the, transcriptional, activity, of, gata1, and, spi1, through, 'protein-protein', interaction])]). relacion([sujeto(['Our', findings, not, only]), verbo([suggest]), complemento([a, function, of, eaf1, on, hematopoiesis, in, 'vivo,', but, also, reveal, a, novel, regulatory, 'pathway,', 'eaf1-foxo3b-gata1/spi1,', that, may, shed, light, on, the, role, of, 'EAF1', in, 'MLL-ELL', induced, leukemogenesis])]). relacion([sujeto(['The', regulatory, consequences, of, 'DNA', methylation, is, context, 'dependent;', it, can, 'induce,', 'enhance,', and]), verbo([suppress]), complemento([gene, 'expression,', or, have, no, effect, on, gene, regulation])]). relacion([sujeto(['Therefore,', it, is, essential, to, account, for, the, genomic, location, of, its, occurrence, and, the, protein, factors, it]), verbo([associates]), complemento([with, to, improve, our, understanding, of, its, function, and, effects])]). relacion([sujeto(['We']), verbo([found]), complemento([compelling, evidence, that, methylation, status, of, 'DNA', sequences, at, 'ERα', binding, sites, is, tightly, coupled, with, 'ERα', activity])]). relacion([sujeto(['Furthermore,', we, predicted, several, transcription, factors, including, 'FOXA1,', 'GATA1,', and, 'SUZ12', to, be]), verbo([associated]), complemento([with, breast, cancer, by, examining, the, methylation, status, of, their, binding, sites, in, breast, cancer])]). relacion([sujeto(['Lastly,', we, determine, that, methylated, 'CpGs', highly, correlated, with, gene, expression, are, enriched, in, regions, 1, kb, or, more, downstream, of, 'TSSs,']), verbo([suggesting]), complemento([more, significant, regulatory, roles, for, 'CpGs', distal, to, gene, 'TSSs'])]). relacion([sujeto(['Our', study]), verbo([provides]), complemento([novel, insights, into, the, role, of, 'ERα', in, breast, cancers])]). relacion([sujeto(['The', 'RNA-binding', protein, 'Elavl1', '(', also, known, as, 'HuR)']), verbo([regulates]), complemento([gene, expression, at, the, posttranscriptional, level])]). relacion([sujeto(['Knockdown', of, 'Elavl1a', using, specific, morpholinos, resulted, in, a, striking]), verbo([loss]), complemento([of, primitive, embryonic, erythropoiesis])]). relacion([sujeto(['The', 3, '\'', -, untranslated, region, '(', 'UTR)', of, gata1, contains, putative, 'Elavl1a-binding', sites, that, support, robust, expression, levels, when, fused, to, a, transfected, luciferase, reporter, 'gene,', and, 'Elavl1a']), verbo([binds]), complemento([the, gata1, 3, '\'', -, 'UTR', sequences, in, a, manner, dependent, on, these, sites])]). relacion([sujeto(['Moreover,', expression, of, a, transgenic, reporter, specifically, in, developing, embryonic, erythroid, cells, is]), verbo([enhanced]), complemento([by, addition, of, the, gata1, 3, '\'', 'UTR', with, intact, 'Elavl1-binding', sites])]). relacion([sujeto(['Injection', of, gata1, messenger, 'RNA', partially, rescues, the, erythropoiesis, defect]), verbo([caused]), complemento([by, 'Elavl1', knockdown])]). relacion([sujeto(['Our', study]), verbo([reveals]), complemento([a, posttranscriptional, regulatory, mechanism, by, which, 'RNA-binding', protein, 'Elavl1a', regulates, embryonic, erythropoiesis, by, maintaining, appropriate, levels, of, gata1, expression])]). relacion([sujeto(['GATA1', mutations, are, tightly]), verbo([associated]), complemento([with, transient, myeloproliferative, disorder, '(', 'TMD)', and, acute, megakaryoblstic, leukemia, '(', 'AMKL)', in, children, with, 'Down', syndrome])]). relacion([sujeto(['Ectopic', expression, of, 'PSTPIP2', impaired, megakaryocytic, differentiation, as, evidenced, by, a]), verbo([decrease]), complemento([of, 'CD41', expression, and, reduced, 'DNA', content, in, 'K562', cells])]). relacion([sujeto(['PSTPIP2', overexpression, also]), verbo([caused]), complemento([enhanced, activation, of, 'Src', family, kinases, and, subsequently, reduced, 'ERK', phosphorylation])]). relacion([sujeto(['Moreover,', the, 'W232A', mutant, of, 'PSTPIP2,', defective, in, its, interaction, with, 'PEST', family, phosphatases, that]), verbo([recruit]), complemento(['c-Src', terminal, kinase, '(', 'CSK)', to, suppress, 'Src', family, 'kinases,', failed, to, inhibit, differentiation, and, lost, its, ability, to, enhance, 'Src', family, kinases, or, reduce, 'ERK', phosphorylation])]). relacion([sujeto(['In', 'fact,', the, 'W232A', mutant, of, 'PSTPIP2']), verbo([promoted]), complemento([megakaryocyte, differentiation])]). relacion([sujeto(['These', observations]), verbo([suggest]), complemento([that, 'PSTPIP2', recruiting, 'PEST', phosphatases, somehow, blocked, 'CSK', activity, and, led, to, enhanced, activation, of, 'Src', family, kinases, and, reduced, 'ERK', 'phosphorylation,', which, ultimately, repressed, megakaryocyte, differentiation])]). relacion([sujeto(['Supporting', this, 'idea,', 'PSTPIP2']), verbo([interacted]), complemento([with, 'LYN', and, the, expression, of, a, dominant, negative, 'LYN', '(', 'LYN', 'DN)', overwhelmed, the, inhibitory, effect, of, 'PSTPIP2', on, differentiation, and, 'ERK', signaling])]). relacion([sujeto(['In', 'addition,', a, constitutively, active, 'LYN', '(', 'LYN', 'CA)', normalized, the]), verbo([enhanced]), complemento([megakaryocyte, differentiation, and, repressed, 'ERK', signaling, in, 'PSTPIP2', knockdown, cells])]). relacion([sujeto(['Finally,', we]), verbo([found]), complemento([that, 'PSTPIP2', repressed, 'ERK', 'signaling,', 'differentiation,', and, proliferation, and, verified, that, 'PSTPIP2', upregulation, repressed, megakaryocyte, development, in, primary, mouse, bone, marrow, cells])]). relacion([sujeto(['Our', study, thus]), verbo([reveals]), complemento([a, novel, mechanism, by, which, dysregulation, of, 'PSTPIP2', due, to, 'GATA-1', deficiency, may, contribute, to, abnormal, megakaryocyte, proliferation, and, differentiation, in, pathogenesis, of, related, diseases])]). relacion([sujeto(['Mutations', in, the, gene, 'RPSA,', which, encodes, ribosomal, protein, 'SA,']), verbo([cause]), complemento([more, than, half, of, the, cases, of, isolated, congenital, asplenia])]). relacion([sujeto(['These', 'disease-causing', mutations]), verbo([lead]), complemento([to, haploinsufficiency, of, 'RPSA'])]). relacion([sujeto(['Haploinsufficiency', of, genes, encoding, other, ribosomal, proteins]), verbo([have]), complemento([been, reported, to, cause, other, developmental, defects, in, 'humans,', and, in, model, organisms, like, the, fly, or, the, mouse])]). relacion([sujeto(['One', hypothesis, is, that, the, 'ribosome,', and, ribosomal, proteins, in, 'particular,']), verbo([regulate]), complemento([the, expression, of, specific, genes, during, development])]). relacion([sujeto(['Using', critical, factors, to]), verbo([induce]), complemento([imERYPCs, provides, a, model, of, erythrocyte, biogenesis, that, could, potentially, contribute, to, a, stable, supply, of, erythrocytes, for, 'donor-independent', transfusion])]). relacion([sujeto(['P-TEFb', activation, classically, occurs, by, a, 'feedback-regulated', process, of, 'signal-induced,', reversible]), verbo([release]), complemento([of, active, 'Cdk9-cyclin', 'T', modules, from, 'large,', inactive, 7, 'SK', small, nuclear, ribonucleoprotein, particle, '(', 'snRNP)', complexes])]). relacion([sujeto(['Here,', we]), verbo([have]), complemento([identified, an, alternative, pathway, of, irreversible, 'P-TEFb', activation, in, megakaryopoiesis, that, is, mediated, 'by dissolution', of, the, 7, 'SK', snRNP, complex])]). relacion([sujeto(['In', this, 'pathway,', calpain, 2, cleavage, of, the, core, 7, 'SK', snRNP, component, 'MePCE']), verbo([promoted]), complemento(['P-TEFb', release, and, consequent, upregulation, of, a, cohort, of, cytoskeleton, remodeling, 'factors,', including, 'α-actinin-1'])]). relacion([sujeto(['Restoring', calpain, 2, expression, in, 'GATA1s', mutant, megakaryocytes, rescued, normal, 'development,', implicating, this, morphogenetic, pathway, as, a]), verbo([target]), complemento([in, human, leukemogenesis])]). relacion([sujeto(['Small', asymmetries, and, stochasticity, intrinsically, present, in, all, genetic, switches]), verbo([lead]), complemento([to, the, effect, of, delayed, bifurcation, which, will, change, the, differentiation, result, according, to, the, timing, of, the, process, and, affect, the, proportion, of, erythroid, versus, myeloid, cells])]). relacion([sujeto(['This', conversion, may]), verbo([have]), complemento([important, contributions, to, the, immune, system, when, the, bias, is, in, favor, of, the, attractor, which, gives, rise, to, 'non-immune', cells])]). relacion([sujeto(['Here,', we]), verbo([report]), complemento([that, the, 'PIAS1', epigenetic, pathway, plays, an, important, role, in, regulating, 'HSC', 'self-renewal', and, differentiation])]). relacion([sujeto(['PIAS1', is]), verbo([required]), complemento([for, maintaining, the, quiescence, of, dormant, 'HSCs', and, the, 'long-term', repopulating, capacity, of, 'HSC'])]). relacion([sujeto(['Pias1', disruption]), verbo([caused]), complemento([the, abnormal, expression, of, 'lineage-associated', genes])]). relacion([sujeto(['As', a, 'result,', 'Pias1', disruption]), verbo([caused]), complemento([the, inappropriate, induction, of, 'Gata1', in, 'HSCs', and, common, lymphoid, progenitors, '(', 'CLPs)'])]). relacion([sujeto(['The', expression, of, other, myeloerythroid, genes, was, also]), verbo([enhanced]), complemento([in, 'CLPs', and, 'lineage-negative', 'progenitors,', with, a, concurrent, repression, of, 'B', 'cell-specific', genes])]). relacion([sujeto(['Consistently,', 'Pias1', disruption]), verbo([caused]), complemento([enhanced, 'myeloerythroid,', but, reduced, 'B', lymphoid, lineage, differentiation])]). relacion([sujeto(['These', results, identify, a, novel, role, of, 'PIAS1', in]), verbo([maintaining]), complemento([the, quiescence, of, dormant, 'HSCs', and, in, the, epigenetic, repression, of, the, myeloerythroid, program])]). relacion([sujeto(['ETV7', is, a, human, oncoprotein, that, cooperates, with, 'Eμ-MYC', to]), verbo([promote]), complemento(['pre-B-cell', leukemia, in, mice])]). relacion([sujeto(['It', is, normally]), verbo([expressed]), complemento([in, the, bone, marrow, and, fetal, liver, and, is, upregulated, in, primary, 'leukemia,', suggesting, that, it, is, involved, in, proper, hematopoiesis, and, leukemogenesis])]). relacion([sujeto(['ETV7']), verbo([has]), complemento([been, deleted, in, most, 'rodents,', but, is, conserved, in, all, other, 'vertebrates,', including, the, 'zebrafish,', 'Danio', rerio])]). relacion([sujeto(['Our', results, demonstrate, that, etv7]), verbo([regulates]), complemento([the, expression, of, the, zebrafish, lanosterol, synthase, '(', 'lss)', 'gene,', an, essential, gene, in, the, cholesterol, synthesis, pathway])]). relacion([sujeto(['Furthermore,', morpholino, knockdown, of, etv7]), verbo([leads]), complemento([to, loss, of, 'hemoglobin-containing', red, blood, 'cells,', a, phenotype, that, can, be, rescued, by, injection, of, exogenous, cholesterol])]). relacion([sujeto(['Vascular', complications, are, the]), verbo([leading]), complemento([cause, of, mortality, and, morbidity, in, patients, with, diabetes])]). relacion([sujeto(['The', zebrafish, model, with, 'HCD-HG', treatment, was, characterized, by, significantly]), verbo([increased]), complemento([tissue, levels, of, 'insulin,', 'glucagon,', 'glucose,', total, triglyceride, and, cholesterol])]). relacion([sujeto(['Confocal', microscopic, analysis, further, revealed, that, the, diabetic, larvae, developed, clearly, thickened, endothelial, 'layers,', distinct, perivascular, lipid, 'depositions,', substantial, accumulations, of, inflammatory, cells, in, the, injured, 'vasculature,', and, a]), verbo([decreased]), complemento([velocity, of, blood, flow])]). relacion([sujeto(['A', combination, of, high, cholesterol, diet, and, high, glucose, exposure]), verbo([induces]), complemento([a, rapid, onset, of, vascular, complications, in, zebrafish, similar, to, the, early, atherosclerotic, vascular, injuries, in, mammalian, diabetic, 'models,', suggesting, that, zebrafish, may, be, used, as, a, novel, animal, model, for, diabetic, vasculopathy])]). relacion([sujeto(['Transient', leukemia, '(', 'TL)', is, evident, in, 5, -, 10, '%', of, all, neonates, with, 'Down', syndrome, '(', 'DS)', and]), verbo([associated]), complemento([with, 'N-terminal', truncating, 'GATA1', mutations, '(', 'GATA1s)'])]). relacion([sujeto(['Here', we]), verbo([report]), complemento([that, 'TL-cell', clones, generate, abundant, eosinophils, in, a, substantial, fraction, of, patients])]). relacion([sujeto(['Similarly,', ectopic, expression, of, 'Gata1s,', but, not, 'Gata1,', in, 'wild-type', 'CD34(+)-hematopoietic', stem, and, progenitor, cells]), verbo([induced]), complemento([hyperproliferation, of, eosinophil, promyelocytes, in, vitro])]). relacion([sujeto(['Although', 'GATA1s']), verbo([retained]), complemento([the, function, of, 'GATA1', to, induce, eosinophil, genes, by, occupying, their, promoter, 'regions,', 'GATA1s', was, impaired, in, its, ability, to, repress, oncogenic, 'MYC', and, the, 'pro-proliferative', 'E2F', transcription, network])]). relacion([sujeto(['In', 'agreement,', terminal, eosinophil, maturation, was, blocked, in, 'Gata1(Δe2)', knockin, 'mice,', exclusively]), verbo([expressing]), complemento(['Gata1s,', leading, to, accumulation, of, eosinophil, precursors, in, blood, and, bone, marrow])]). relacion([sujeto(['These', data]), verbo([suggest]), complemento([a, direct, relationship, between, the, 'N-terminal', truncating, mutations, of, 'GATA1', and, clonal, eosinophilia, in, 'DS', patients])]). relacion([sujeto(['In', this, issue, of, 'Blood,', 'Roberts', et, al]), verbo([report]), complemento([the, comprehensive, screening, of, a, large, cohort, of, 'Down', syndrome, neonates, for, the, transient, abnormal, myelopoiesis, '(', 'TAM)', disorder, based, on, blood, cell, morphology, review, and, screening, for, 'GATA1', 'mutations,', the, signature, genetic, marker, of, 'TAM'])]). relacion([sujeto(['Transcription', factor, '(', 'TF)']), verbo([binding]), complemento([to, 'DNA', can, be, modeled, in, a, number, of, different, ways])]). relacion([sujeto(['In', this, study, a, linear, 'k-mer', model, proposed, for, predicting, 'TF', specificity, in, protein]), verbo([binding]), complemento([microarrays, '(', 'PBM)', is, applied, to, a, 'high-throughput', 'SELEX', data, and, the, question, of, how, to, choose, the, most, informative, 'k-mers', to, the, binding, model, is, studied])]). relacion([sujeto(['We', also]), verbo([found]), complemento([that, the, later, 'SELEX', enrichment, cycles, provide, a, much, better, discrimination, between, bound, and, unbound, sequences, as, model, prediction, accuracies, increased, for, all, proteins, together, with, the, cycle, number])]). relacion([sujeto(['Elucidation', of, the, genetic, pathways, that, control, red, blood, cell, development]), verbo([has]), complemento([been, a, central, goal, of, erythropoiesis, research, over, the, past, decade])]). relacion([sujeto(['Notably,', data, from, several, recent, studies]), verbo([have]), complemento([provided, new, insights, into, the, regulation, of, erythroid, gene, transcription])]). relacion([sujeto(['Transcription', profiling, demonstrates, that, erythropoiesis, is, mainly, controlled, by, a, small, group, of, 'lineage-restricted', transcription, factors, '[', 'Gata']), verbo([binding]), complemento([protein, 1, '(', 'Gata1),', 'T', cell, acute, lymphocytic, leukemia, 1, protein, '(', 'Tal1),', and, 'Erythroid', 'Kruppel-like', factor, '(', 'EKLF;', henceforth, referred, to, as, 'Klf1)]'])]). relacion([sujeto(['Binding-site', mapping, using, 'ChIP-Seq', indicates, that, most, 'DNA-bound', 'Gata1', and, 'Tal1', proteins, are, contained, within, higher, order, complexes, '(', 'Ldb1', 'complexes)', that, include, the]), verbo([nuclear]), complemento([adapters, 'Ldb1', and, 'Lmo2'])]). relacion([sujeto(['Ldb1', complexes]), verbo([regulate]), complemento(['Klf1,', and, 'Ldb1', 'complex-binding', sites, frequently, colocalize, with, 'Klf1', at, erythroid, genes, and, 'cis-regulatory', 'elements,', indicating, strong, functional, synergy, between, 'Gata1,', 'Tal1,', and, 'Klf1'])]). relacion([sujeto(['Together', with, new, data, demonstrating, that, 'Ldb1', can]), verbo([mediate]), complemento(['long-range', 'promoter-enhancer', 'interactions,', these, findings, provide, a, foundation, for, the, first, comprehensive, models, of, the, global, regulation, of, erythroid, gene, transcription])]). relacion([sujeto(['Here', we, show, that, aggf1]), verbo([acts]), complemento([at, the, top, of, the, genetic, regulatory, hierarchy, in, the, specification, of, hemangioblasts, in, zebrafish])]). relacion([sujeto(['Knockdown', of, aggf1, expression]), verbo([decreases]), complemento([expression, of, endothelial, 'cell-specific', markers, '(', 'cdh5,', 'admr)', and, disrupts, primitive, hematopoiesis, as, shown, by, a, decreased, number, of, erythroid, cells, and, reduced, expression, of, gata1, '(', marker, for, erythroid, 'progenitors)', and, pu])]). relacion([sujeto(['Aggf1', knockdown, also]), verbo([decreases]), complemento([expression, of, runx1, and, 'c-myb,', indicating, that, it, is, required, for, specification, of, hematopoietic, stem, cells, '(', definitive, 'hematopoiesis)'])]). relacion([sujeto(['Aggf1', knockdown]), verbo([led]), complemento([to, dramatically, reduced, expression, of, hemangioblast, markers, 'fli1,', 'etsrp,', 'lmo2,', and, 'scl,', and, 'hematopoietic/endothelial', defects, in, aggf1, morphants, were, rescued, by, messenger, 'RNA', for, 'scl,', 'fli-vp16,', or, etsrp])]). relacion([sujeto(['Taken', 'together,', these, data, indicate, that, aggf1, is]), verbo([involved]), complemento([in, differentiation, of, both, hematopoietic, and, endothelial, lineages, and, that, aggf1, acts, upstream, of, 'scl,', 'fli1,', and, etsrp, in, specification, of, hemangioblasts])]). relacion([sujeto(['We']), verbo([report]), complemento([here, the, unusual, case, of, a, newborn, without, 'Down', syndrome, who, presented, neonatal, transient, leukemia, and, who, achieved, spontaneously, complete, remission])]). relacion([sujeto(['CD235', '(', 'glycophorin)', 'expression,', a, marker, of, erythroid, 'differentiation,', was, significantly]), verbo([increased]), complemento([by, 'NH2Cl', and, 'U0126,', along, with, an, increase, in, cd235, mRNA, levels])]). relacion([sujeto(['Other', erythroid, markers, such, as, 'γ-globin', and, 'CD71', '(', transferrin, 'receptor)', were, also]), verbo([increased]), complemento([by, 'NH2Cl', and, 'U0126'])]). relacion([sujeto(['In', 'contrast,', 'CD61', '(', integrin, 'β3)', and, 'CD42b', '(', 'GP1bα)', 'expression,', markers, of, megakaryocytic, 'differentiation,', was]), verbo([increased]), complemento([by, 'staurosporine,', but, did, not, change, significantly, by, 'NH2Cl', and, 'U0126'])]). relacion([sujeto(['NH2Cl', retarded, cell, proliferation, without, a, marked]), verbo([loss]), complemento([of, viability])]). relacion([sujeto(['Paradoxically,', 'NH2Cl', and, 'staurosporine,', but, not, 'U0126,']), verbo([induced]), complemento([large, cells, with, multiple, or, lobulated, 'nuclei,', which, was, characteristic, to, megakaryocytes])]). relacion([sujeto(['NH2Cl']), verbo([increased]), complemento([the, mRNA, levels, of, gata1, and, 'scl,', decreased, that, of, 'gata2,', and, did, not, change, those, of, pu])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, 'NH2Cl', induces, the, bidirectional, differentiation, of, 'K562'])]). relacion([sujeto(['Oxidative', stress, may, be, effective, in]), verbo([inducing]), complemento([leukemic, cell, differentiation])]). relacion([sujeto(['In', this, issue, of, 'Blood,', 'Takai', et, al]), verbo([provide]), complemento([some, tantalizing, clues, on, how, expression, of, the, 'GATA1', transcription, 'factor,', a, master, regulator, of, 'erythroid/megakaryocytic', 'differentiation,', is, suppressed, in, the, hematopoietic, 'stem/progenitor', cell, '(', 'HSPC)', compartment])]). relacion([sujeto(['It']), verbo([has]), complemento([been, reported, that, patients, with, 'Down', syndrome, '(', 'DS)', frequently, develop, transient, myeloproliferative, disorder, '(', 'TMD)', and, less, commonly, myeloid, leukemia, in, 'DS', '(', 'ML-DS)'])]). relacion([sujeto(['To', better, understand, the, events, that]), verbo([lead]), complemento([to, 'TAL1', expression, in, hematopoiesis, and, in, 'T-ALL,', we, studied, looping, interactions, at, the, 'TAL1', locus])]). relacion([sujeto(['Loss', of, 'GATA1', results, in, disassembly, of, the, hub, and]), verbo([loss]), complemento([of, 'CTCF/RAD21', from, one, of, its, insulators])]). relacion([sujeto(['We', identified, looping, patterns, unique, to, 'TAL1-expressing', 'T-ALL', 'cells,', 'and,', 'intriguingly,', loops, occurring, between, the, 'TAL1', and, 'STIL', genes, at, the, common, 'TAL1/STIL', breakpoints]), verbo([found]), complemento([in, 'T-ALL'])]). relacion([sujeto(['Erythropoiesis', is]), verbo([regulated]), complemento([at, multiple, levels, to, ensure, the, proper, generation, of, mature, red, cells, under, multiple, physiological, conditions])]). relacion([sujeto(['By', integrating, 'genome-wide', surveys, of, chromatin, 'states,', transcription, factor, 'occupancy,', and, tissue, expression, 'patterns,', we, identify, multiple, lncRNAs, that, are, dynamically]), verbo([expressed]), complemento([during, 'erythropoiesis,', show, epigenetic, 'regulation,', and, are, targeted, by, key, erythroid, transcription, factors, 'GATA1,', 'TAL1,', or, 'KLF1'])]). relacion([sujeto(['We', focus, on, 12, such, candidates, and]), verbo([find]), complemento([that, they, are, 'nuclear-localized', and, exhibit, complex, developmental, expression, patterns])]). relacion([sujeto(['Depleting', them, severely, impaired, erythrocyte, 'maturation,']), verbo([inhibiting]), complemento([cell, size, reduction, and, subsequent, enucleation])]). relacion([sujeto(['One', of, 'them,', 'alncRNA-EC7,', is]), verbo([transcribed]), complemento([from, an, enhancer, and, is, specifically, needed, for, activation, of, the, neighboring, gene, encoding, 'BAND', 3])]). relacion([sujeto(['Our', study]), verbo([provides]), complemento([an, annotated, catalog, of, erythroid, 'lncRNAs,', readily, available, through, an, online, 'resource,', and, shows, that, diverse, types, of, lncRNAs, participate, in, the, regulatory, circuitry, underlying, erythropoiesis])]). relacion([sujeto(['Patients', with, 'Down\'s', 'Syndrome']), verbo([have]), complemento([a, higher, risk, of, developing, acute, megakaryoblastic, leukemia, '(', 'AML)'])]). relacion([sujeto(['Ten', per, cent, of, newborn, infants, with, this, syndrome]), verbo([have]), complemento([transient, abnormal, myelopoiesis, '(', 'TAM),', indistinguishable, from, 'AML,', which, generally, remits, spontaneously])]). relacion([sujeto(['The', transcription, factors, 'SCL/TAL1,', 'RUNX1,', 'RUNX2', and, 'GATA2', were]), verbo([expressed]), complemento([in, both, the, 'CD45(+)', and, 'CD45(-)', 'SVF', 'populations;', 'however,', in, contrast, to, our, observations, in, the, 'CD34(+)', cells, from, 'CB', and, adult, 'PB,', 'GATA1', was, not, detected])]). relacion([sujeto(['The', analysis, of, 'BFU-E-derived', colonies, revealed, that, virtually, all, erythroid, cells, produced, by, 'SVF', cells]), verbo([expressed]), complemento([fetal, 'hemoglobin,', and, the, 'γ-globin', mRNA, levels, ranged, between, those, obtained, in, the, 'adult-', and, 'neonatal-derived', erythroid, cells])]). relacion([sujeto(['Our', results, demonstrate, that, hematopoietic, progenitors, in, 'SVF']), verbo([have]), complemento([molecular, and, functional, features, that, differ, from, those, exhibited, by, circulating, 'progenitors,', suggesting, the, possibility, of, a, different, origin])]). relacion([sujeto(['Patients', with, primary, myelofibrosis]), verbo([have]), complemento([increased, risk, for, bleeding, and, thrombosis])]). relacion([sujeto(['It', is, debated, whether, propensity, to, thrombosis, is, due, to]), verbo([increased]), complemento([numbers, of, platelet, microparticles, 'and/or', to, pathological, 'platelet-neutrophil', interactions])]). relacion([sujeto(['Platelet', neutrophil, interactions, are]), verbo([mediated]), complemento([by, 'P-selectin', and, even, though, the, megakaryocytes, of, myelofibrosis, patients, express, normal, levels, of, 'P-selectin,', it, remains, abnormally, localized, to, the, demarcation, membrane, system, rather, than, being, assembled, into, the, 'α-granules', in, platelets])]). relacion([sujeto(['Mice', carrying, the, hypomorphic, 'Gata1(low)', mutation]), verbo([express]), complemento([the, same, megakaryocyte, abnormalities, presented, by, primary, myelofibrosis, 'patients,', including, abnormal, 'P-selectin', localization, to, the, 'DMS', and, develop, with, age, 'myelofibrosis,', a, disease, that, closely, resembles, human, primary, myelofibrosis])]). relacion([sujeto(['Whether', these, mice, would, also, develop, thrombosis]), verbo([has]), complemento([not, been, investigated, as, yet])]). relacion([sujeto(['Taken', together, these, data, indicate, that, abnormal, localization, of, 'P-selectin,']), verbo([induced]), complemento([by, the, 'Gata1(low)', 'mutation,', and, 'thus,', increased, pathological, interactions, with, 'leucocytes,', is, responsible, for, the, increased, presence, of, thrombosis, seen, in, these, mice])]). relacion([sujeto(['GATA-1,', the, founding, member, of, the, 'GATA', family, of, transcription, 'factors,']), verbo([has]), complemento([been, demonstrated, to, play, crucial, roles, in, the, differentiation, of, erythroid, 'cells,', 'magakaryocytes,', 'eosinophils,', and, mast, cells])]). relacion([sujeto(['Here', we, show, that, basophils, abundantly]), verbo([express]), complemento(['Gata1', 'mRNAs,', and, that, 'siRNA-mediated', knockdown, of, 'Gata1', resulted, in, impaired, production, of, 'IL-4', by, basophils, in, response, to, the, stimulation, with, 'IgE', plus, antigens])]). relacion([sujeto(['ΔdblGATA', mice, that, carry, the, mutated, 'Gata1', promoter, and, are, widely, used, for, functional, analysis, of, eosinophils, owing, to, their, selective]), verbo([loss]), complemento([of, eosinophils, showed, a, decreased, number, of, basophils, with, reduced, expression, of, 'Gata1', mRNAs])]). relacion([sujeto(['ΔdblGATA', basophils]), verbo([responded]), complemento([poorly, ex, vivo, to, stimulation, with, 'IgE', plus, antigens, compared, with, 'wild-type', basophils, as, assessed, by, degranulation, and, production, of, 'IL-4', and, 'IL-6'])]). relacion([sujeto(['The', stem, cell, protein, 'SALL4', plays, a, critical, role, in, hematopoiesis, by]), verbo([regulating]), complemento([the, cell, fate])]). relacion([sujeto(['In', primitive, hematopoietic, 'precursors,', it]), verbo([activates]), complemento([or, represses, important, genes, via, recruitment, of, various, epigenetic, factors, such, as, 'DNA', 'methyltransferases,', and, histone, deacylases])]). relacion([sujeto(['Here,', we, demonstrate, that, 'LSD1,', a, histone, lysine, 'demethylase,', also]), verbo([participates]), complemento([in, the, 'trans-repressive', effects, of, 'SALL4'])]). relacion([sujeto(['Based', on, luciferase, 'assays,', the, amine, oxidase, domain, of, 'LSD1', is, important, in]), verbo([suppressing]), complemento(['SALL4-mediated', reporter, transcription])]). relacion([sujeto(['In', freshly, isolated, adult, mouse, bone, 'marrows,', both, 'SALL4', and, 'LSD1', proteins, are, preferentially]), verbo([expressed]), complemento([in, undifferentiated, progenitor, cells, and, 'co-localize', in, the, nuclei])]). relacion([sujeto(['Further', sequential, chromatin, immunoprecipitation, assay, confirmed, that, these, two, factors, share, the, same]), verbo([binding]), complemento([sites, at, the, promoter, regions, of, important, hematopoietic, regulatory, genes, including, 'EBF1,', 'GATA1,', and, 'TNF'])]). relacion([sujeto(['In', 'addition,', studies, from, both, 'gain-', and, 'loss-of-function', models, revealed, that, 'SALL4', dynamically, controls, the]), verbo([binding]), complemento([levels, of, 'LSD1,', which, is, accompanied, by, a, reversely, changed, histone, 3, dimethylated, lysine, 4, at, the, same, promoter, regions])]). relacion([sujeto(['Finally,', 'shRNA-mediated', knockdown, of, 'LSD1', in, hematopoietic, precursor, cells, resulted, in, altered, 'SALL4', downstream, gene, expression, and]), verbo([increased]), complemento([cellular, activity])]). relacion([sujeto(['Thus,', our, data, revealed, that, histone, demethylase, 'LSD1', may, negatively]), verbo([regulate]), complemento(['SALL4-mediated', 'transcription,', and, the, dynamic, regulation, of, 'SALL4-associated', epigenetic, factors, cooperatively, modulates, early, hematopoietic, precursor, proliferation])]). relacion([sujeto(['The', discovery, that, an, abnormally]), verbo([activated]), complemento(['JAK-STAT', signaling, pathway, is, central, to, the, pathogenesis, of, myeloproliferative, neoplasms, has, promoted, the, clinical, development, of, 'small-molecule', 'JAK2', inhibitors])]). relacion([sujeto(['These', agents]), verbo([have]), complemento([shown, remarkable, efficacy, in, disease, 'control,', but, do, not, induce, molecular, 'remission;', on, the, other, 'hand,', interferon, holds, the, promise, to, target, the, putative, hematopoietic, progenitor, cell, initiating, the, disease])]). relacion([sujeto(['The', presence, of, additional, molecular, abnormalities, indicates, a, high, molecular, complexity, of, myeloproliferative, 'neoplasms,', and, the, need, for, simultaneously]), verbo([targeting]), complemento([different, targets])]). relacion([sujeto([1, axis, to, 'explore,', at, the, systems, 'level,', dynamic, relationships, between, transcription, factor, '(', 'TF)']), verbo([binding]), complemento([and, global, gene, expression, programs, as, multipotent, cells, differentiate])]). relacion([sujeto(['Our', analysis]), verbo([reveals]), complemento(['(', 1, ')', differential, complexity, of, sequence, motifs, bound, by, 'GATA1,', 'GATA2,', and, 'PU'])]). relacion([sujeto([1, ;, '(', 2, ')', the, scope, and, interplay, of, 'GATA1', and, 'GATA2', programs, 'within,', and, during, transitions, 'between,', different, cell, 'compartments,', and, the, extent, of, their, 'hard-wiring', by, 'DNA', 'motifs;', '(', 3, ')', the, potential, to, predict, gene, expression, trajectories, based, on, global, associations, between, 'TF-binding', data, and]), verbo([target]), complemento([gene, 'expression;', and, '(', 4, ')', how, dynamic, modeling, of, 'DNA-binding', and, gene, expression, data, can, be, used, to, infer, regulatory, logic, of, 'TF', circuitry])]). relacion([sujeto(['Gata1', hematopoietic, regulatory, domain, '(', 'G1HRD)']), verbo([has]), complemento([been, shown, to, recapitulate, endogenous, 'Gata1', gene, expression, in, transgenic, mouse, assays, in, vivo])]). relacion([sujeto(['Mutation', of, 'CP2-binding', sites, also, moderately]), verbo([decreased]), complemento(['G1HRD', activity])]). relacion([sujeto(['The', combined, mutation, of, the, 'CP2-binding', sites, and, the, 'GATA-palindrome', motif, resulted, in, complete]), verbo([loss]), complemento([of, 'G1HRD', activity])]). relacion([sujeto(['This']), verbo([leads]), complemento([to, autoimmune, responses, against, 'RBCs', in, aged, mice, that, are, similar, to, autoimmune, hemolytic, anemia, '(', 'AIHA)'])]). relacion([sujeto(['We', examined, whether, a, 'SOD1', deficiency, 'and/or', the, human, 'SOD1', transgene, '(', 'hSOD1)', would, affect, phenotypes, of, 'AIHA-prone', 'New', 'Zealand', 'Black', '(', 'NZB)', mice, by, establishing, three, congenic, 'strains:', those, lacking, 'SOD1,', those]), verbo([expressing]), complemento([hSOD1, under, a, 'GATA-1', 'promoter,', and, those, lacking, mouse, 'SOD1', but, expressing, hSOD1])]). relacion([sujeto(['These', data]), verbo([suggest]), complemento([that, oxidative, stress, in, 'RBCs', may, be, an, underlying, mechanism, for, autoimmune, responses, in, 'NZB', mice])]). relacion([sujeto(['These', results, were, consistent, with, the, hypothetical, role, of, reactive, oxygen, species, in]), verbo([triggering]), complemento([the, autoimmune, reaction, in, 'RBCs', and, may, provide, a, novel, approach, to, mitigating, the, progression, of, 'AIHA', by, reducing, oxidative, stress])]). relacion([sujeto(['The', prognostic, impact, of, mutations, in, the, 'CCAAT/enhancer']), verbo([binding]), complemento([protein, α, '(', 'CEBPA)', gene, was, evaluated, in, the, context, of, concomitant, molecular, mutations, and, cytogenetic, aberrations, in, acute, myeloid, leukemia, '(', 'AML)'])]). relacion([sujeto(['Pathogenesis', of, these, 'Down', 'syndrome-related', myeloid, disorders, is, poorly, 'understood,', except, for, 'GATA1', mutations]), verbo([found]), complemento([in, most, cases])]). relacion([sujeto(['Here', we]), verbo([report]), complemento([genomic, profiling, of, 41, 'TAM,', 49, 'DS-AMKL', and, 19, 'non-DS-AMKL', 'samples,', including, 'whole-genome', 'and/or', 'whole-exome', sequencing, of, 15, 'TAM', and, 14, 'DS-AMKL', samples])]). relacion([sujeto(['TAM', appears, to, be]), verbo([caused]), complemento([by, a, single, 'GATA1', mutation, and, constitutive, trisomy, 21])]). relacion([sujeto(['Subsequent', 'AMKL', evolves, from, a, 'pre-existing', 'TAM', clone, through, the, acquisition, of, additional, 'mutations,', with, major, mutational]), verbo([targets]), complemento([including, multiple, cohesin, components, '(', 53, '%', ')', ',', 'CTCF', '(', 20, '%', ')', ',', and, 'EZH2,', 'KANSL1', and, other, epigenetic, regulators, '(', 45, '%', ')', ',', as, well, as, common, signaling, 'pathways,', such, as, the, 'JAK', family, 'kinases,', 'MPL,', 'SH2B3', '(', 'LNK)', and, multiple, 'RAS', pathway, genes, '(', 47, '%', ')'])]). relacion([sujeto(['The', aim, of, the, present, study, was, to, investigate, the, role, of, each, estrogen, receptors, on, the, regulation, of, proteins]), verbo([involved]), complemento([with, proliferation, and, differentiation, of, 'Sertoli', cells, from, 15, -, 'day-old', rats])]). relacion([sujeto(['Activation', of, 'ESR1', by, 17, 'β-estradiol', '(', 'E2)', and, 'ESR1-selective', agonist, 'PPT']), verbo([increased]), complemento(['CCND1', 'expression,', and, this, effect, was, dependent, on, 'NF-kB', activation])]). relacion([sujeto(['Analyzing', the, expression, of, 'ESR1', and, 'ESR2', in, different, stages, of, development, of, 'Sertoli', 'cells,', we, observed, that, the, 'ESR1/ESR2', ratio]), verbo([decreased]), complemento([with, 'age,', and, this, ratio, seems, to, be, important, to, determine, the, end, of, cell, proliferation, and, the, start, of, cell, differentiation])]). relacion([sujeto(['In', 'Sertoli', cells, from, 15, -, 'day-old', 'rats,', the, 'ESR1/ESR2', ratio, favors, the, effect, of, 'ESR1', and, the, activation, of, this, receptor]), verbo([increased]), complemento(['[', 'Methyl-(3)H]thymidine', incorporation])]). relacion([sujeto(['We', propose, that, in, 'Sertoli', cells, from, 15, -, 'day-old', rats, 'E2']), verbo([modulates]), complemento(['Sertoli', cell, proliferation, through, 'ESR1/NF-kB-mediated', increase, of, 'CCND1,', and, cell, cycle, exit, and, differentiation, through, 'ESR2/CREB-mediated', increase, of, 'CDKN1B,', 'GATA-1', and, 'DMRT1'])]). relacion([sujeto(['By', 'now,', considerable, progress]), verbo([has]), complemento([been, made, in, elucidating, 'GATA', 'factor-dependent', genetic, networks, that, control, red, blood, cell, development])]). relacion([sujeto(['Here', we]), verbo([reported]), complemento([that, 'GATA-1', and, 'GATA-2', 'co-regulated', the, expression, of, two, microRNA, 'genes,', 'microRNA-27a', and, 'microRNA-24,', with, critical, roles, in, regulating, erythroid, differentiation])]). relacion([sujeto(['As', erythropoiesis, 'proceeded,', 'GATA-1', directly]), verbo([activated]), complemento(['miR-27a≈24', 'transcription,', and, this, involved, a, 'GATA-1-mediated', displacement, of, 'GATA-2', from, 'chromatin,', a, process, termed, '\'', 'GATA', 'switch\''])]). relacion([sujeto(['Furthermore,', the, mature, 'miR-27a', and, 'miR-24', cooperatively]), verbo([inhibited]), complemento(['GATA-2', translation, and, favoured, the, occupancy, switch, from, 'GATA-2', to, 'GATA-1,', thus, completing, a, positive, feedback, loop, to, promote, erythroid, maturation])]). relacion([sujeto(['In', line, with, the, essential, role, of, 'GATA', 'factors,', ectopic, expression, of, 'miR-27a', or, 'miR-24']), verbo([promoted]), complemento([erythropoiesis, in, human, primary, 'CD34+', haematopoietic, progenitor, cells, and, 'mice,', whereas, attenuated, 'miR-27', or, 'miR-24', level, led, to, impaired, erythroid, phenotypes, in, haematopoietic, progenitor, cells, and, zebrafish])]). relacion([sujeto(['Taken', 'together,', these, data, integrated, micro, 'RNA', expression, and, function, into, 'GATA', factor, coordinated, networks, and]), verbo([provided]), complemento([mechanistic, insight, into, a, regulatory, circuit, that, comprised, 'GATA1/2', switch, and, 'miR-27a/24', in, erythropoiesis])]). relacion([sujeto(['However,', the, 'GFP', expression, was, aberrantly]), verbo([increased]), complemento([in, the, 'HSCs', and, was, associated, with, decreases, in, 'DNA', methylation, and, abundant, 'GATA2', binding, to, the, transgenic, 'MG-GFP', allele])]). relacion([sujeto(['The', 3.2, -, kb, sequences, interspaced, between, the, 'Gata1', hematopoietic, enhancer, and, the, double, 'GATA-motif', were, able, to]), verbo([recruit]), complemento(['DNA', methyltransferase, 1, ',', thereby, exerting, a, 'cis-repressive', function, in, the, 'HSC-like', cell, line])]). relacion([sujeto(['These', results, indicate, that, the, 3.2, -, kb, interspacing, sequences, inactivate, 'Gata1', by]), verbo([maintaining]), complemento(['DNA-methylation', in, the, 'HSCs'])]). relacion([sujeto(['Furthermore', 'low-abundance', 'GATA1', mutant, clones, were, detected, by]), verbo([targeted]), complemento(['next-generation', resequencing, '(', 'NGS)', in, 18, of, 88, '(', 20.4, '%', ;, sensitivity, '∼0'])]). relacion([sujeto(['We']), verbo([suggest]), complemento([the, term, &, 'quot;silent', 'TAM"', for, neonates, with, 'DS', with, 'GATA1', mutations, detectable, only, by, 'NGS'])]). relacion([sujeto(['To', identify, all, babies, at, risk, of, 'ML-DS,', we]), verbo([suggest]), complemento(['GATA1', mutation, and, blood, count, and, smear, analyses, should, be, performed, in, 'DS', neonates])]). relacion([sujeto(['The', development, of, 'DS-TMD', and, 'DS-AMKL']), verbo([requires]), complemento([not, only, the, presence, of, the, trisomy, 21, but, also, that, of, 'GATA1', mutations])]). relacion([sujeto(['Despite', extensive, studies, into, the, genetics, of, 'DS-AMKL,', the, importance, of, epigenetic, deregulation, in, this, disease]), verbo([has]), complemento([been, unexplored])]). relacion([sujeto(['These', early, changes, are, characterized, by, marked]), verbo([loss]), complemento([of, 'DNA', methylation, at, genes, associated, with, developmental, 'disorders,', including, those, affecting, the, 'cardiovascular,', 'neurological,', and, endocrine, systems])]). relacion([sujeto(['This', is, followed, by, a, second, wave, of, changes, detected, in, 'DS-TMD', and, 'DS-AMKL,', characterized, by]), verbo([gains]), complemento([of, methylation])]). relacion([sujeto(['This', new, wave, of, hypermethylation]), verbo([targets]), complemento([a, distinct, set, of, genes, involved, in, hematopoiesis, and, regulation, of, cell, growth, and, proliferation])]). relacion([sujeto(['Our', previous, study, demonstrated, that, benzene, 'metabolites,', including, phenol, and, 'hydroquinone,']), verbo([inhibited]), complemento(['hemin-induced', erythroid, differentiation, of, 'K562', cells])]). relacion([sujeto(['In', present, 'study,', to, elucidate, the, role, of, 'DNA', methylation, in, benzene, 'metabolites-induced', inhibition, on, erythroid, 'differentiation,', it, was, investigated, whether, 'DNA', methyltransferase, 'inhibitor,', 5, -, 'aza-2\'-deoxycytidine', '(', 5, -, 'aza-CdR),', was, able, to]), verbo([prevent]), complemento([benzene, metabolites, inhibiting, 'hemin-induced', erythroid, differentiation, in, 'K562', 'cells,', and, the, methylation, levels, of, 'erythroid-specific', genes, in, benzene, 'metabolites-treated', 'K562', cells, were, analyzed, by, 'Quantitative', 'MassARRAY', methylation, analysis, platform])]). relacion([sujeto(['It', was]), verbo([found]), complemento([that, treatment, of, 'K562', cells, with, 5, -, 'aza-CdR', completely, prevented, phenol, and, hydroquinone, inhibiting, 'hemin-induced', hemoglobin, synthesis, and, 'hemin-induced', expression, of, erythroid, specific, 'genes,', including, 'α-', and, 'β-globin,', erythroid, porphobilinogen, deaminase, and, 'GATA', binding, protein, 1, '(', 'GATA-1)'])]). relacion([sujeto(['Consistently,', the, exposure, to, benzene, metabolites]), verbo([caused]), complemento([an, increase, in, 'DNA', methylation, levels, at, a, few, 'CpG', sites, in, some, erythroid, specific, 'genes,', including, 'α-globin', gene, and, 'α-cluster', 'HS40', 'element,', 'β-globin', gene, and, 'HS', core, sequence, in, 'LCR', of, 'β-globin', gene, 'cluster,', erythroid, porphobilinogen, deaminase, 'gene,', and, 'GATA-1', gene])]). relacion([sujeto(['These', results, indicated, that, 'DNA', methylation, played, a, role, in, benzene, metabolites]), verbo([inhibiting]), complemento(['hemin-induced', erythroid, differentiation, of, 'K562', cells, via, 'down-regulating', transcription, of, some, erythroid, related, genes])]). relacion([sujeto(['The', establishment, and, maintenance, of, cell, 'type-specific', transcriptional, programs]), verbo([require]), complemento([an, ensemble, of, broadly, expressed, chromatin, remodeling, and, modifying, enzymes])]). relacion([sujeto(['We']), verbo([have]), complemento([been, addressing, this, problem, in, the, context, of, erythrocyte, development, driven, by, the, transcription, factor, 'GATA-1', and, its, coregulator, 'Friend', of, 'GATA-1', '(', 'FOG-1)'])]). relacion([sujeto(['As', certain, 'GATA-1']), verbo([target]), complemento([genes, have, little, to, no, 'FOG-1', requirement, for, 'expression,', presumably, additional, coregulators, can, mediate, 'GATA-1', function])]). relacion([sujeto(['GATA-1', selectively]), verbo([induced]), complemento(['H4', monomethylated, lysine, 20, at, 'repressed,', but, not, 'activated,', 'loci,', and, endogenous, 'SetD8', mediated, 'GATA-1-dependent', repression, of, a, cohort, of, its, target, genes])]). relacion([sujeto(['GATA-1', used, different, combinations, of, 'SetD8,', 'FOG-1,', and, the, 'FOG-1-interacting', nucleosome, remodeling, and, deacetylase, complex, component, 'Mi2β', to, repress, distinct]), verbo([target]), complemento([genes])]). relacion([sujeto(['Implicating', 'SetD8', as, a, 'context-dependent', 'GATA-1', corepressor, expands, the, repertoire, of, coregulators]), verbo([mediating]), complemento(['establishment/maintenance', of, the, erythroid, cell, genetic, 'network,', and, provides, a, biological, framework, for, dissecting, the, cell, 'type-specific', functions, of, this, important, coregulator])]). relacion([sujeto(['We', propose, a, coregulator, matrix, model, in, which, distinct, combinations, of, chromatin, regulators, are]), verbo([required]), complemento([at, different, 'GATA-1', target, 'genes,', and, the, unique, attributes, of, the, target, loci, mandate, these, combinations])]). relacion([sujeto(['Erythroid-specific', 5, -, aminolevulinate, synthase, '(', 'ALAS2)', is, the, 'rate-limiting', enzyme, for, heme, biosynthesis, in, erythroid, 'cells,', and, a, missense, mutation, of, the, 'ALAS2', gene, is]), verbo([associated]), complemento([with, congenital, sideroblastic, anemia])]). relacion([sujeto(['The', newly, identified, enhancer, contains, a, 'cis-acting', element, that, is]), verbo([bound]), complemento([by, the, 'erythroid-specific', transcription, factor, 'GATA1,', as, confirmed, by, chromatin, immunoprecipitation, analysis, in, vivo, and, by, electrophoretic, mobility, shift, assay, in, vitro])]). relacion([sujeto(['A', promoter, activity, assay, in, 'K562', human, erythroleukemia, cells, revealed, that, the, presence, of, this, 130, -, base, pair, region]), verbo([increased]), complemento([the, promoter, activity, of, the, 'ALAS2', gene, by, 10, -, 15, -, fold])]). relacion([sujeto(['Moreover,', 'GATA1', failed, to]), verbo([bind]), complemento([to, each, mutant, sequence, at, the, 'GATA-binding', 'site,', and, each, mutation, abolished, the, enhancer, function, on, 'ALAS2', promoter, activity, in, 'K562', cells])]). relacion([sujeto(['Thus,', a, mutation, at, the, 'GATA-binding', site, in, this, enhancer, may]), verbo([cause]), complemento([congenital, sideroblastic, anemia])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, the, newly, identified, intronic, enhancer, is, essential, for, the, expression, of, the, 'ALAS2', gene, in, erythroid, cells])]). relacion([sujeto(['Recent', work, using, primary, human, foetal, liver, and, bone, marrow, 'cells,', human, embryonic, stem, cells, and, iPS, cells, shows, that, prior, to, acquisition, of, 'GATA1', 'mutations,', trisomy, 21, itself, alters, human, foetal, haematopoietic, stem, cell, and, progenitor, cell, biology]), verbo([causing]), complemento([multiple, abnormalities, in, myelopoiesis, and, 'B-lymphopoiesis'])]). relacion([sujeto(['Eosinophil-produced', cytokines]), verbo([have]), complemento([been, shown, to, participate, in, the, maintenance, of, 'antigen-specific', plasma, cells, '(', 'PC)', in, bone, marrow, '(', 'BM),', suggesting, that, eosinophils, are, required, in, the, development, 'and/or', maintenance, of, alloantibody, responses, posttransplant])]). relacion([sujeto(['These', differences, were]), verbo([associated]), complemento([with, modestly, lower, titers, of, serum, 'DSA', 4, and, 12, weeks, after, sensitization, but, secondary, immunizations, induced, similar, increases, in, both, groups])]). relacion([sujeto(['Therefore,', eosinophils, are, not]), verbo([required]), complemento([for, alloantibody, formation, or, maintenance, in, mice, and, are, thus, unlikely, to, be, effective, targets, for, antibody, desensitization])]). relacion([sujeto(['Transcription', factor, 'GATA2', is, highly]), verbo([expressed]), complemento([in, hematopoietic, stem, cells, and, 'progenitors,', whereas, its, expression, declines, after, erythroid, commitment, of, progenitors])]). relacion([sujeto(['In', 'contrast,', the, start, of, 'GATA1', expression, coincides, with, the, erythroid, commitment, and]), verbo([increases]), complemento([along, with, the, erythroid, differentiation])]). relacion([sujeto(['In', 'Gata1-knockdown', embryos, that, concomitantly]), verbo([express]), complemento(['Gata2-GFP', 'reporter,', 'high-level', expression, of, 'GFP', reporter, was, detected, in, accumulated, immature, hematopoietic, cells, with, impaired, 'differentiation,', demonstrating, that, 'GATA1', represses, 'Gata2', gene, expression, in, hematopoietic, progenitors, in, vivo])]). relacion([sujeto(['We']), verbo([have]), complemento([conducted, chromatin, immunoprecipitation, '(', 'ChIP)', on, microarray, analyses, of, 'GATA2', and, 'GATA1,', and, results, indicate, that, the, 'GATA1-binding', sites, widely, overlap, with, the, sites, 'pre-occupied', by, 'GATA2', before, the, 'GATA1', expression])]). relacion([sujeto(['Importantly,', erythroid, genes, harboring, 'GATA', boxes]), verbo([bound]), complemento([by, both, 'GATA1', and, 'GATA2', tend, to, be, expressed, in, immature, erythroid, 'cells,', whereas, those, harboring, 'GATA', boxes, to, which, 'GATA1', binds, highly, but, 'GATA2', binds, only, weakly, are, important, for, the, mature, erythroid, cell, function])]). relacion([sujeto(['Our', results, thus, support, the, contention, that, preceding]), verbo([binding]), complemento([of, 'GATA2', helps, the, following, binding, of, 'GATA1', and, thereby, secures, smooth, expression, of, the, 'transient-phase', genes])]). relacion([sujeto(['It']), verbo([has]), complemento([been, found, that, 'Gata1', gene, knockdown, heterozygous, female, '(', 'Gata1(G1'])]). relacion([sujeto(['In', this, 'study,', we]), verbo([have]), complemento([generated, a, novel, 'Gata1', knockdown, erythroblastic, cell, 'line,', designated, 'GAK14,', from, the, leukemia, cells, in, the, 'Gata1(G1'])]). relacion([sujeto(['Although', 'GAK14', cells]), verbo([maintain]), complemento([immature, phenotype, on, 'OP9', stromal, cells, in, the, presence, of, erythropoietin, and, stem, cell, 'factor,', the, cells, produce, 'Gr-1-,', 'Mac1-,', 'B220-,', 'CD3e-', or, 'CD49b-positive', hematopoietic, cells, when, 'co-cultured', with, 'DAS104-8', feeder, cells])]). relacion([sujeto(['It']), verbo([has]), complemento([been, previously, shown, that, acute, myeloid, leukemia, '(', 'AML)', patients, with, higher, levels, of, 'GATA1', expression, have, poorer, outcomes])]). relacion([sujeto(['Furthermore,', pediatric, 'Down', syndrome, '(', 'DS)', patients, with, acute, megakaryocytic, leukemia, '(', 'AMKL),', whose, blast, cells, almost, universally, harbor, somatic, mutations, in, exon, 2, of, the, transcription, factor, gene, 'GATA1,', demonstrate]), verbo([increased]), complemento([overall, survival, relative, to, 'non-DS', pediatric, 'patients,', suggesting, a, potential, role, for, 'GATA1', in, chemotherapy, response])]). relacion([sujeto(['ShRNA', knockdown, of, 'GATA1', in, the, megakaryocytic, cell, line, 'Meg-01', resulted, in, significantly]), verbo([increased]), complemento([cytarabine, '(', 'ara-C)', and, daunorubicin, 'anti-proliferative', sensitivities, and, decreased, 'Bcl-xL', transcript, and, protein, levels])]). relacion([sujeto(['Chromatin', immunoprecipitation, '(', 'ChIP)', and, reporter, gene, assays, demonstrated, that, the, 'Bcl-x', gene, '(', which]), verbo([transcribes]), complemento([the, 'Bcl-xL', 'transcripts)', is, a, bona, fide, 'GATA1', target, gene, in, 'AMKL', cells])]). relacion([sujeto(['Treatment', of, the, 'Meg-01', cells, with, the, histone, deacetylase, inhibitor, valproic, acid, resulted, in, 'down-regulation', of, both, 'GATA1', and, 'Bcl-xL', and, significantly]), verbo([enhanced]), complemento(['ara-C', sensitivity])]). relacion([sujeto(['Furthermore,', additional, 'GATA1']), verbo([target]), complemento([genes, were, identified, by, oligonucleotide, microarray, and, 'ChIP-on-Chip', analyses])]). relacion([sujeto(['Our', findings, demonstrate, a, role, for, 'GATA1', in, chemotherapy, resistance, in, 'non-DS', 'AMKL', 'cells,', and, identified, additional, 'GATA1']), verbo([target]), complemento([genes, for, future, studies])]). relacion([sujeto(['Somatic', mutations]), verbo([leading]), complemento([to, the, exclusive, production, of, a, short, 'GATA1', isoform, '(', 'GATA1s)', occur, in, all, cases, of, 'DS-TMD', and, 'DS-AMKL'])]). relacion([sujeto(['Mice', engineered, to, exclusively, produce, 'GATA1s']), verbo([have]), complemento([marked, megakaryocytic, progenitor, '(', 'MkP)', hyperproliferation, during, early, fetal, liver, '(', 'FL)', 'hematopoiesis,', but, not, during, postnatal, 'BM', 'hematopoiesis,', mirroring, the, spontaneous, resolution, of, 'DS-TMD'])]). relacion([sujeto(['Here,', we]), verbo([report]), complemento([a, striking, upregulation, of, type, 'I', 'IFN-responsive', gene, expression, in, prospectively, isolated, mouse, 'BM-', versus, 'FL-derived', 'MkPs'])]). relacion([sujeto(['Conversely,', deletion, of, the, 'α/β', 'IFN', receptor, 1, '(', 'Ifnar1)', gene, or, injection, of, neutralizing, 'IFN-α/β', antibodies]), verbo([increased]), complemento([the, proliferation, of, 'BM-derived', 'MkPs', of, 'GATA1s', mice, beyond, the, initial, postnatal, period])]). relacion([sujeto(['We', also]), verbo([found]), complemento([that, these, differences, existed, in, human, 'FL', versus, 'BM', megakaryocytes, and, that, primary, 'DS-TMD', cells, expressed, type, 'I', 'IFN-responsive', genes])]). relacion([sujeto(['We', propose, that]), verbo([increased]), complemento([type, 'I', 'IFN', signaling, contributes, to, the, developmental, 'stage-specific', effects, of, 'GATA1s', and, possibly, the, spontaneous, resolution, of, 'DS-TMD'])]). relacion([sujeto(['Current', analytical, approaches, for, 'ChIP-seq', analysis, are, largely, geared, towards, 'single-sample', 'investigations,', and]), verbo([have]), complemento([limited, applicability, in, comparative, settings, that, aim, to, identify, combinatorial, patterns, of, enrichment, across, multiple, datasets])]). relacion([sujeto(['The', physiological, switch, in, expression, of, the, 'embryonic,', 'fetal,', and, adult, 'β-like', globin, genes]), verbo([has]), complemento([garnered, enormous, attention, from, investigators, interested, in, transcriptional, mechanisms, and, the, molecular, basis, of, hemoglobinopathies])]). relacion([sujeto(['These', efforts]), verbo([have]), complemento([led, to, the, discovery, of, cell, 'type-specific', transcription, 'factors,', unprecedented, mechanisms, of, transcriptional, coregulator, 'function,', genome, biology, 'principles,', unique, contributions, of, nuclear, organization, to, transcription, and, cell, 'function,', and, promising, therapeutic, targets])]). relacion([sujeto(['Given', the, vast, literature, accrued, on, this, 'topic,', this, article, will, focus, on, the, master, regulator, of, erythroid, cell, development, and, function, 'GATA-1,', its]), verbo([associated]), complemento(['proteins,', and, its, frontline, role, in, controlling, hemoglobin, synthesis])]). relacion([sujeto(['The', disease]), verbo([has]), complemento([been, associated, with, point, mutations, and, large, deletions, in, ten, ribosomal, protein, '(', 'RP)', genes, 'RPS19,', 'RPS24,', 'RPS17,', 'RPL35A,', 'RPL5,', 'RPL11,', 'RPS7,', 'RPS10,', 'RPS26,', and, 'RPL26', and, 'GATA1', in, about, 60, -, 65, '%', of, patients])]). relacion([sujeto(['Here,', we]), verbo([report]), complemento([a, novel, large, deletion, in, 'RPL15,', a, gene, not, previously, implicated, to, be, causative, in, 'DBA'])]). relacion([sujeto(['Like', 'RPL26,', 'RPL15', presents, the, distinctive, feature, of, being]), verbo([required]), complemento([both, for, 60, 'S', subunit, formation, and, for, efficient, cleavage, of, the, internal, transcribed, spacer, 1])]). relacion([sujeto(['In', 'addition,', we, detected, five, deletions, in, 'RP', genes, in, which, mutations]), verbo([have]), complemento([been, previously, shown, to, cause, 'DBA:', one, each, in, 'RPS19,', 'RPS24,', and, 'RPS26,', and, two, in, 'RPS17'])]). relacion([sujeto(['Pre-ribosomal', 'RNA', processing, was, affected, in, cells, established, from, the, patients, bearing, these, 'deletions,']), verbo([suggesting]), complemento([a, possible, molecular, basis, for, their, pathological, effect])]). relacion([sujeto(['These', data, identify, 'RPL15', as, a, new, gene]), verbo([involved]), complemento([in, 'DBA', and, further, support, the, presence, of, large, deletions, in, 'RP', genes, in, 'DBA', patients])]). relacion([sujeto(['Hypermethylation', of, the, promoter, regions, of, the, two, main, human, 'LTBP4', transcriptional, 'forms,', 'LTBP4L', and, 'LTBP4S,', was]), verbo([found]), complemento([to, be, involved, in, 'LTBP4', silencing])]). relacion([sujeto(['Detailed', investigations, of, the, methylation, patterns, of, the, promoter, regions, of, 'LTBP4L', and, 'LTBP4S', identified, 'GATA1,', 'SP1,', 'E2F4', and, 'SMAD3', as, potential, transcription, factors]), verbo([involved]), complemento([in, 'LTBP4', expression])]). relacion([sujeto(['Data']), verbo([suggest]), complemento([that, 'GATA1', mutations, alone, are, sufficient, for, clonal, 'expansions,', and, additional, driver, mutations, at, the, 'TMD', stage, do, not, necessarily, predict, 'AMKL', progression])]). relacion([sujeto(['Later', in, 'infancy,', leukemic, progression]), verbo([requires]), complemento([&, 'quot;third-hit', 'driver"', 'mutations/somatic', 'copy-number', alterations, found, in, 'non-DS', leukemias])]). relacion([sujeto(['Putative', driver, mutations, affecting, 'WNT', '(', 'wingless-related', integration, 'site),', 'JAK-STAT', '(', 'Janus', 'kinase/signal', transducer, and, activator, of, 'transcription),', or, 'MAPK/PI3K', '(', 'mitogen-activated', 'kinase/phosphatidylinositol-3', 'kinase)', pathways, were]), verbo([found]), complemento([in, all, 'cases,', aberrant, activation, of, which, converges, on, overexpression, of, 'MYC'])]). relacion([sujeto(['Erythropoiesis', is, a, tightly]), verbo([regulated]), complemento([process, which, becomes, decoupled, from, its, normal, differentiation, program, in, patients, with, polycythemia, vera, '(', 'PV)'])]). relacion([sujeto(['Somatic', mutations, in, 'JAK2', are, commonly]), verbo([associated]), complemento([with, this, myeloid, proliferative, disorder])]). relacion([sujeto(['To']), verbo([gain]), complemento([insight, into, the, molecular, events, that, are, required, for, abnormally, developing, erythroid, cells, to, escape, dependence, on, normal, growth, 'signals,', we, performed, in, vitro, expansion, of, mature, erythroblasts, '(', 'ERY)', from, seven, normal, healthy, donors, and, from, seven, polycythemic, patients, in, the, presence, of, 'IL3,', 'EPO,', 'SCF', for, 10, ',', 11, ',', or, 13, days])]). relacion([sujeto(['Normal', 'ERYs']), verbo([required]), complemento([exposure, to, the, glucocorticoid, dexamethasone, '(', 'Dex)', for, 'expansion,', while, 'PV-derived', 'ERYs', expanded, in, the, absence, of, dexamethasone])]). relacion([sujeto(['Our', results, show, that, normal, 'ERYs', displayed, greater, levels, of, phosphorylation, of, 'EGFR,', 'PDGFRβ,', 'TGFβ,', and, 'cKit,', while, 'PV-derived', 'ERYs', were, characterized, by]), verbo([increased]), complemento([phosphorylation, of, cytoplasmic, kinases, in, the, 'JAK/STAT,', 'PI3K,', and, 'GATA1', pathways])]). relacion([sujeto(['Together', these, data]), verbo([suggest]), complemento([that, 'PV', erythroblast, expansion, and, maturation, may, be, maintained, and, enriched, in, the, absence, of, dexamethasone, through, reduced, 'TAL1', expression, and, by, accessing, additional, signaling, cascades])]). relacion([sujeto(['Members', of, this, acquired, repertoire, may]), verbo([provide]), complemento([important, insight, into, the, pathogenesis, of, aberrant, erythropoiesis, in, myeloproliferative, neoplasms, such, as, polycythemia, vera])]). relacion([sujeto(['It', is]), verbo([caused]), complemento([by, an, expansion, of, fetal, 'megakaryocyte-erythroid', progenitors, '(', 'MEPs)', triggered, by, trisomy, of, chromosome, 21, and, is, further, enhanced, by, the, somatic, acquisition, of, a, mutation, in, 'GATA1'])]). relacion([sujeto(['To', examine, the, hypothesis, that, the, 'Hsa21', 'ETS', transcription, factor, 'ERG', cooperates, with, 'GATA1s', in, this, 'process,', we, generated, 'double-transgenic', mice]), verbo([expressing]), complemento([hERG, and, 'Gata1s'])]). relacion([sujeto(['We', show, that]), verbo([increased]), complemento([expression, of, 'ERG', by, itself, is, sufficient, to, induce, expansion, of, 'MEPs', in, fetal, livers])]). relacion([sujeto(['Gata1s', expression, synergizes, with, 'ERG', in]), verbo([enhancing]), complemento([the, expansion, of, fetal, 'MEPs', and, megakaryocytic, 'precursors,', resulting, in, hepatic, 'fibrosis,', transient, postnatal, 'thrombocytosis,', 'anemia,', a, gene, expression, profile, that, is, similar, to, that, of, human, 'TMD', and, progression, to, progenitor, myeloid, leukemia, by, 3, months, of, age])]). relacion([sujeto(['The', human, relevance, of, this]), verbo([finding]), complemento([is, underscored, by, the, recent, discovery, of, similar, mutations, in, 'GATA1', in, patients, with, 'Diamond-Blackfan', anemia])]). relacion([sujeto(['We', previously]), verbo([reported]), complemento([that, 'IL-3', signaling, induces, phosphorylation, of, 'GATA-1', at, the, 'serine²⁶', 'position,', which, contributes, to, 'IL-3-mediated', 'anti-apoptotic', response])]). relacion([sujeto(['Here,', we, demonstrate, that, phosphorylation, of, 'GATA-1', at, 'serine²⁶', is, also, transiently]), verbo([induced]), complemento([in, cells, of, the, erythroid, lineage, '(', primary, erythroblasts, and, 'erythrocyte-committed', progenitors, '[', 'EPs])', by, erythropoietin, '(', 'EPO),', the, principal, cytokine, regulating, erythropoiesis])]). relacion([sujeto(['To', examine, whether, phosphorylation, of, 'GATA-1', at, 'serine²⁶', would]), verbo([have]), complemento([any, impact, on, 'erythropoiesis,', mutant, mice, carrying, either, a, glutamic, acid, '(', 'GATA-1(S26E))', or, alanine, '(', 'GATA-1(S26A))', substitution, at, 'serine²⁶', were, generated])]). relacion([sujeto(['However,', a, moderate, reduction, in, the, 'CFU-E', progenitor, population, was, consistently, observed, in, the, bone, marrow, of, 'GATA-1(S26E),', but, not, 'GATA-1(S26A)', 'mice,']), verbo([suggesting]), complemento([that, such, defect, was, compensated, for, within, the, bone, marrow])]). relacion([sujeto(['Taken', 'together,', these, results]), verbo([suggest]), complemento([that, 'EPO-induced', transient, phosphorylation, of, 'GATA-1', at, 'serine²⁶', is, dispensable, for, erythropoiesis])]). relacion([sujeto(['Hematopoiesis', -, the, process, by, which, blood, cells, are, formed, -]), verbo([has]), complemento([been, studied, intensely, for, over, a, century, using, a, variety, of, model, systems])]). relacion([sujeto(['Over', the, last, 'decade,', the, zebrafish]), verbo([has]), complemento([come, to, the, forefront, as, a, new, model, in, hematopoiesis, 'research,', as, it, allows, the, use, of, 'large-scale', 'genetics,', chemical, screens, and, transgenics])]). relacion([sujeto(['This', comparative, approach, to, understanding, hematopoiesis]), verbo([has]), complemento([led, to, fundamental, knowledge, about, the, process, and, to, the, development, of, new, therapies, for, disease])]). relacion([sujeto(['Here,', we]), verbo([provide]), complemento([a, broad, overview, of, vertebrate, hematopoiesis])]). relacion([sujeto(['We', investigated, how, these, alterations]), verbo([cause]), complemento([distinct, clinical, phenotypes, by, combining, 'structural,', 'biochemical,', and, genomic, approaches, with, gene, complementation, systems, that, examine, 'GATA1', function, in, biologically, relevant, cellular, contexts])]). relacion([sujeto(['Substitutions', that, disrupt, 'FOG1', cofactor]), verbo([binding]), complemento([impair, both, gene, activation, and, repression, and, are, associated, with, pronounced, clinical, phenotypes])]). relacion([sujeto(['Surprisingly,', 2, mutations, shown, to, impair, 'DNA']), verbo([binding]), complemento([of, 'GATA1', in, vitro, did, not, measurably, affect, in, vivo, target, gene, occupancy])]). relacion([sujeto(['Rather,', one, of, these, disrupted]), verbo([binding]), complemento([to, the, 'TAL1', 'complex,', implicating, it, in, diseases, caused, by, 'GATA1', mutations])]). relacion([sujeto(['Notably,', different, substitutions, at, the, same, amino, acid, can, selectively]), verbo([inhibit]), complemento(['TAL1', complex, or, 'FOG1', 'binding,', producing, distinct, cellular, and, clinical, phenotypes])]). relacion([sujeto(['Erythropoiesis', is, finely]), verbo([regulated]), complemento([by, two, major, 'cytokines,', stem, cell, factor, '(', 'SCF)', and, erythropoietin, '(', 'Epo)'])]). relacion([sujeto(['Therefore,', molecular, abnormalities]), verbo([associated]), complemento([with, decrease, of, 'HSP70', expression, in, the, nucleus, may, result, in, ineffective, erythropoiesis, characterized, by, apoptosis, and, impaired, maturation, of, erythroid, precursors])]). relacion([sujeto(['These', findings, open, new, potential]), verbo([targeted]), complemento([therapies, for, erythroid, disorders])]). relacion([sujeto(['Real', time, reverse, 'transcription-ploymerase', chain, reaction, analysis, indicated, that, overexpression, of, lmo2]), verbo([increased]), complemento([the, expression, of, hematopoietic, 'genes(gata1,', 'tal1,', 'Β-h1,', and, 'Β-major', 'globin)', during, 'EB', formation])]). relacion([sujeto(['LMO2']), verbo([enhances]), complemento([the, proliferation, and, differentiation, of, hemangioblasts])]). relacion([sujeto(['However,', the, molecular, mechanisms, underlying, the, maintenance, and, differentiation, of, 'HSCs']), verbo([have]), complemento([not, been, fully, elucidated])]). relacion([sujeto(['Here,', we, show, that, zebrafish, 'Ddx46,', encoding, a, 'DEAD-box', 'RNA', 'helicase,', is]), verbo([expressed]), complemento([in, 'HSCs', of, the, caudal, hematopoietic, tissue, '(', 'CHT)'])]). relacion([sujeto(['The', number, of, 'HSCs']), verbo([expressing]), complemento([the, molecular, markers, cmyb, or, 'T-cell', acute, lymphocytic, leukemia, 1, '(', 'tal1)', was, markedly, reduced, in, 'Ddx46', mutants])]). relacion([sujeto(['We']), verbo([found]), complemento([that, myelopoiesis, 'occurred,', but, erythropoiesis, and, lymphopoiesis, were, 'suppressed,', in, 'Ddx46', mutants])]). relacion([sujeto(['Taken', 'together,', our, results]), verbo([provide]), complemento([the, first, genetic, evidence, that, zebrafish, 'Ddx46', is, required, for, the, multilineage, differentiation, of, 'HSCs', during, 'development,', through, the, regulation, of, specific, gene, expressions])]). relacion([sujeto(['Several', erythroid, genes]), verbo([have]), complemento([been, shown, to, require, all, 3, factors, for, their, 'expression,', suggesting, that, they, function, 'synergistically;', 'however,', there, is, little, direct, evidence, for, widespread, cooperation])]). relacion([sujeto(['Ldb1', proteins, are, capable, of, 'coassociation,', and, 'long-range', 'Ldb1-mediated', oligomerization, of, 'enhancer-', and, 'promoter-bound', 'Ldb1', complexes]), verbo([has]), complemento([been, shown, to, be, required, for, 'β-globin', gene, expression])]). relacion([sujeto(['In', this, 'study,', we, generated, a, genomewide, map, of, 'Ldb1', complex]), verbo([binding]), complemento([sites, that, revealed, widespread, binding, at, erythroid, genes, and, at, known, erythroid, enhancer, elements])]). relacion([sujeto(['Ldb1', complex]), verbo([binding]), complemento([sites, frequently, colocalized, with, 'Klf1', binding, sites, and, with, consensus, binding, motifs, for, other, erythroid, transcription, factors])]). relacion([sujeto(['Transcriptomic', analysis, demonstrated, a, strong, correlation, between, 'Ldb1', complex]), verbo([binding]), complemento([and, 'Ldb1', dependency, for, gene, expression, and, identified, a, large, cohort, of, genes, coregulated, by, 'Ldb1', complexes, and, 'Klf1'])]). relacion([sujeto(['Together,', these, results]), verbo([provide]), complemento([a, foundation, for, defining, the, mechanism, and, scope, of, 'Ldb1', complex, activity, during, erythropoiesis])]). relacion([sujeto(['Here', we, show, that, platelet, integrin, 'CD41', '(', 'αIIb),', currently, thought, to, only, transiently, mark, fetal, 'HSCs,', is]), verbo([expressed]), complemento([on, an, adult, 'HSC', subtype, that, accumulates, with, age])]). relacion([sujeto(['CD41-knockout', '(', 'KO)', mice, displayed, multilineage, hematopoietic, defects, coupled, with]), verbo([decreased]), complemento([quiescence, and, survival, of, 'HSCs,', suggesting, that, 'CD41', is, functionally, relevant, for, 'HSC', maintenance, and, hematopoietic, homeostasis])]). relacion([sujeto(['Transplantation', experiments, indicated, that, 'CD41-KO-associated', defects, are, 'long-term', 'transplantable,', 'HSC-derived', 'and,', in, 'part,']), verbo([mediated]), complemento([through, the, loss, of, platelet, mass, leading, to, decreases, in, 'HSC', exposure, to, important, platelet, released, 'cytokines,', such, as, transforming, growth, factor, β1])]). relacion([sujeto(['In', 'summary,', our, data]), verbo([provide]), complemento([a, novel, marker, to, identify, a, 'myeloid-biased', 'HSC', subtype, that, becomes, prevalent, with, age, and, highlights, the, dogma, of, 'HSC', regulation, by, their, progeny])]). relacion([sujeto(['Recently,', an, erythroid, 'cell-specific', regulatory, element]), verbo([has]), complemento([been, identified, in, the, first, intron, of, 'ABO', using, luciferase, reporter, assays, with, 'K562', cells])]). relacion([sujeto(['In', 'addition,', partial, deletion, of, 'Intron', 1, including, the, element, was, observed, in, genomic, 'DNAs', obtained, from, 111, 'Bm', and, 'ABm', 'individuals,', except, for, 'one,', whereas, the, deletion, was, never]), verbo([found]), complemento([among, 1005, individuals, with, the, common, phenotypes])]). relacion([sujeto(['In', this, 'study,', further, investigation, was, performed, to]), verbo([reveal]), complemento([the, underlying, mechanism, responsible, for, reduction, of, 'B', antigen, expression, in, the, exceptional, 'Bm', individual])]). relacion([sujeto(['Electrophoretic', mobility, assays, and, promoter, assays, were, performed, to, examine, whether, a, nucleotide, substitution, reduced, the]), verbo([binding]), complemento([of, a, transcription, factor, and, induced, loss, of, function, of, the, element])]). relacion([sujeto(['The', electrophoretic, mobility, shift, assays, showed, that, the, mutation, abolished, the]), verbo([binding]), complemento([of, 'GATA', transcription, 'factors,', and, the, promoter, assays, demonstrated, complete, loss, of, enhancer, activity, of, the, element])]). relacion([sujeto(['These', observations]), verbo([suggest]), complemento([that, the, mutation, in, the, 'GATA', motif, of, the, 'erythroid-specific', regulatory, element, may, diminish, the, binding, of, 'GATA', transcription, factors, and, down, regulate, transcriptional, activity, of, the, element, on, the, 'B', 'allele,', leading, to, reduction, of, 'B', antigen, expression, in, erythroid, lineage, cells, of, the, 'Bm', individual])]). relacion([sujeto(['Amplification', of, 'MYCN', '(', 'N-Myc)', oncogene]), verbo([has]), complemento([been, reported, as, a, frequent, event, and, a, poor, prognostic, marker, in, human, acute, myeloid, leukemia, '(', 'AML)'])]). relacion([sujeto(['N-Myc', downstream]), verbo([regulated]), complemento([gene, 1, '(', 'NDRG1),', negatively, controlled, by, 'MYCN', in, human, and, functionally, involved, in, neutrophil, 'maturation,', was, significantly, 'under-expressed', in, this, model])]). relacion([sujeto(['Using', peripheral, blood, smear, 'detection,', histological, section, and, flow, cytometric, analysis, of, single, cell, suspension, from, kidney, and, 'spleen,', we]), verbo([found]), complemento([that, 'MYCN', overexpression, promoted, cell, 'proliferation,', enhanced, the, repopulating, activity, of, myeloid, cells, and, the, accumulation, of, immature, hematopoietic, blast, cells])]). relacion([sujeto(['MYCN']), verbo([enhanced]), complemento([primitive, hematopoiesis, by, upregulating, scl, and, lmo2, expression, and, promoted, myelopoiesis, by, inhibiting, gata1, expression, and, inducing, pu])]). relacion([sujeto(['The', above, results]), verbo([induced]), complemento([by, overexpression, of, 'MYCN', closely, resemble, the, main, aspects, of, human, 'AML,', suggesting, that, 'MYCN', plays, a, role, in, the, etiology, of, 'AML'])]). relacion([sujeto(['MYCN', reprograms, hematopoietic, cell, fate, by]), verbo([regulating]), complemento(['NDRG1', and, several, 'lineage-specific', hematopoietic, transcription, factors])]). relacion([sujeto(['Epidermal', 'Langerhans', cells, '(', 'LC)']), verbo([expressing]), complemento([the, 'high-affinity', receptor, for, 'IgE', '(', 'FcεRI)', play, a, key, role, in, atopic, dermatitis, '(', 'AD)'])]). relacion([sujeto(['To', study, a, putative, impact, of, 'TLR2', signaling, on, 'FcεRI,', we, analyzed, 'FcεRI', and, known, transcription, factors, of, the, receptor, after, ligand]), verbo([binding]), complemento([to, 'TLR2'])]). relacion([sujeto(['We', generated, 'LC', from, 'CD34(+)', progenitors, in, vitro, '(', 'CD34LC)']), verbo([expressing]), complemento(['FcεRI', and, 'TLR2', as, well, as, its, partners, 'TLR1', and, 'TLR6'])]). relacion([sujeto([1, ',', thus]), verbo([suggesting]), complemento([that, 'FcεRI', is, controlled, by, 'PU'])]). relacion([sujeto(['Leishmania', donovani, is, a, parasite, that]), verbo([causes]), complemento([visceral, leishmaniasis, by, infecting, and, replicating, in, macrophages, of, the, bone, 'marrow,', 'spleen,', and, liver])]). relacion([sujeto(['Severe', anemia, and, leucopenia, is]), verbo([associated]), complemento([with, the, disease])]). relacion([sujeto(['Although', immune, defense, mechanisms, against, the, parasite]), verbo([have]), complemento([been, 'studied,', we, have, a, limited, understanding, of, how, 'L'])]). relacion([sujeto(['Anemia', was]), verbo([associated]), complemento([with, increased, levels, of, serum, 'erythropoietin,', which, indicates, the, hamsters, respond, to, the, anemia, by, producing, erythropoietin])]). relacion([sujeto(['We']), verbo([found]), complemento([that, infection, also, increased, numbers, of, 'BFU-E', and, 'CFU-E', progenitor, populations, in, the, spleen, and, bone, marrow, and, differentially, altered, erythroid, gene, expression, in, these, organs])]). relacion([sujeto(['In', the, bone, 'marrow,', the, mRNA, expression, of, erythroid, differentiation, genes, '(', 'α-globin,', 'β-globin,', 'ALAS2)', were]), verbo([inhibited]), complemento([by, 50, '%', ',', but, mRNA, levels, of, erythroid, receptor, '(', 'c-kit,', 'EpoR)', and, transcription, factors, '(', 'GATA1,', 'GATA2,', 'FOG1)', were, not, affected, by, the, infection])]). relacion([sujeto(['This']), verbo([suggests]), complemento([that, infection, has, a, negative, effect, on, differentiation, of, erythroblasts])]). relacion([sujeto(['In', the, 'spleen,', erythroid, gene, expression, was]), verbo([enhanced]), complemento([by, 'infection,', indicating, that, the, anemia, activates, a, stress, erythropoiesis, response, in, the, spleen])]). relacion([sujeto(['Analysis', of, cytokine, mRNA, levels, in, spleen, and, bone, marrow]), verbo([found]), complemento([that, 'IFN-γ', mRNA, is, highly, increased, by, 'L'])]). relacion([sujeto(['Since', 'TRAIL']), verbo([induces]), complemento([erythroblasts, 'apoptosis,', apoptosis, of, bone, marrow, erythroblasts, from, infected, hamsters, was, examined, by, flow, cytometry])]). relacion([sujeto(['Percentage', of, erythroblasts, that, were, apoptotic, was, significantly]), verbo([increased]), complemento([by, 'L'])]). relacion([sujeto(['Together,', our, results]), verbo([suggest]), complemento([that, 'L'])]). relacion([sujeto([donovani, infection]), verbo([inhibits]), complemento([erythropoiesis, in, the, bone, marrow, by, 'cytokine-mediated', apoptosis, of, erythroblasts])]). relacion([sujeto(['We']), verbo([report]), complemento([the, genomic, occupancy, profiles, of, the, key, hematopoietic, transcription, factor, 'GATA-1', in, 'pro-erythroblasts', and, mature, erythroid, cells, fractionated, from, day, 'E12'])]). relacion([sujeto(['Integration', of, 'GATA-1', occupancy, profiles, with, available, 'genome-wide', transcription, factor, and, epigenetic, profiles, assayed, in, fetal, liver, cells, enabled, as, to, evaluate, 'GATA-1', involvement, in]), verbo([modulating]), complemento([local, chromatin, structure, of, target, genes, during, erythroid, differentiation])]). relacion([sujeto(['Our', results]), verbo([suggest]), complemento([that, 'GATA-1', associates, preferentially, with, changes, of, specific, epigenetic, 'modifications,', such, as, 'H4K16,', 'H3K27', acetylation, and, 'H3K4', 'di-methylation'])]). relacion([sujeto(['Furthermore,', we, used, random, forest, '(', 'RF)', 'non-linear', regression, to, predict, changes, in, the, expression, levels, of, 'GATA-1']), verbo([target]), complemento([genes, based, on, the, genomic, features, available, for, 'pro-erythroblasts', and, mature, fetal, 'liver-derived', erythroid, cells])]). relacion([sujeto(['Thus,', our, study, of, 'GATA-1', 'genome-wide', occupancy, profiles, in, mouse, primary, erythroid, cells, and, their, integration, with, global, epigenetic, marks]), verbo([reveals]), complemento([three, clusters, of, 'GATA-1', gene, targets, that, are, associated, with, specific, epigenetic, signatures, and, functional, characteristics])]). relacion([sujeto(['Compared', to, 'wild-type', 'littermates,', 'Pim1-Tx', mice, showed]), verbo([enhanced]), complemento([hematopoiesis, as, demonstrated, by, increased, numbers, of, 'Lin(-)', 'Sca-1', '(', +, ')', 'c-Kit', '(', +, ')', '(', 'LSK)', hematopoietic, 'stem/progenitor', cells, and, cobblestone, area, forming, 'cells,', higher, 'BrdU', incorporation, in, 'long-term', 'HSC', 'population,', and, a, better, ability, to, reconstitute, lethally, irradiated, mice])]). relacion([sujeto(['Mechanistic', studies, demonstrated, an, important, role, of, 'Pim1', kinase, in]), verbo([regulating]), complemento(['HSC', cell, proliferation, and, survival])]). relacion([sujeto(['Our', data]), verbo([provide]), complemento([the, first, direct, evidence, for, the, important, role, of, 'Pim1', kinase, in, the, regulation, of, 'HSCs'])]). relacion([sujeto(['However,', in, serial, 'transplantations,', engrafted, 'TAM-derived', cells, showed, the, emergence, of, divergent, subclones, with, another, 'GATA1', mutation, and, various, 'CNAs,', including, a, 16, q, deletion, and, 1, q, 'gain,', which, are, clinically]), verbo([associated]), complemento([with, 'ML-DS'])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, genetically, heterogeneous, subclones, with, varying, 'leukemia-initiating', potential, already, exist, in, the, neonatal, 'TAM', 'phase,', and, 'ML-DS', may, develop, from, a, pool, of, such, minor, clones, through, clonal, selection])]). relacion([sujeto(['Our', xenograft, model, of, 'TAM', may]), verbo([provide]), complemento([unique, insight, into, the, evolutionary, process, of, leukemia])]). relacion([sujeto(['Erythropoietin', is, the, principal, regulator, of, erythropoiesis, and]), verbo([promotes]), complemento([the, 'survival,', proliferation, and, differentiation, of, erythroid, progenitor, cells, in, mammals])]). relacion([sujeto(['In', this, study, we]), verbo([report]), complemento([on, the, molecular, and, functional, characterization, of, erythropoietin, from, the, goldfish])]). relacion([sujeto(['There', was, no, marked, change, of, epo, expression, in, goldfish, primary, kidney, macrophage, 'cultures,', as, progenitor, cell, to, macrophage, development, 'progressed,', indicating, that, erythropoietin, is, not]), verbo([involved]), complemento([in, monopoiesis])]). relacion([sujeto(['Recombinant', goldfish, erythropoietin]), verbo([induced]), complemento([proliferation, of, progenitor, cells, in, a, 'dose-dependent', 'manner,', and, 'up-regulated', the, expression, of, erythroid, transcription, factors, gata1, and, lmo2, in, progenitor, cells])]). relacion([sujeto(['Furthermore,', recombinant, goldfish, erythropoietin]), verbo([stimulated]), complemento([erythroid, colony, formation, in, a, 'dose-dependent', manner, and, promoted, survival, of, erythroid, progenitor, cells, as, 'colony-forming', cells])]). relacion([sujeto(['Our', results, demonstrate, that, the, function, of, erythropoietin, in, the, goldfish, is, similar, to, that, of, mammals, and]), verbo([suggest]), complemento([a, highly, conserved, mechanism, of, early, erythrocyte, development, in, lower, and, higher, vertebrates])]). relacion([sujeto(['Primary', myelofibrosis, '(', 'PMF)', is, characterized, by, 'fibrosis,', ineffective, hematopoiesis, in, 'marrow,', and, hematopoiesis, in, extramedullary, sites, and, is]), verbo([associated]), complemento([with, abnormal, megakaryocyte, '(', 'MK)', development, and, increased, transforming, growth, factor, '(', 'TGF)-β1', release])]). relacion([sujeto(['David-pathway', analyses, identified, alterations, of, 'TGF-β1,', 'Hedgehog,', and, p53, signaling, in, marrow, and, spleen, and, of, mammalian]), verbo([target]), complemento([of, rapamycin, '(', 'mTOR)', in, spleen, only, and, predicted, that, these, alterations, would, induce, consequences, consistent, with, the, 'Gata1(low)', phenotype, '(', increased, apoptosis, and, 'G1', arrest, both, in, marrow, and, spleen, and, increased, osteoblast, differentiation, and, reduced, 'ubiquitin-mediated', proteolysis, in, marrow, 'only)'])]). relacion([sujeto(['These', data, identify, altered, expression, signatures, of, 'TGF-β1', signaling, that, may, be, responsible, for, 'MF', in, 'Gata1(low)', mice, and, may, represent, additional]), verbo([targets]), complemento([for, therapeutic, intervention, in, 'PMF'])]). relacion([sujeto(['The', intense, physiologic, demand, to, generate, vast, numbers, of, red, blood, cells]), verbo([requires]), complemento([the, establishment, of, a, complex, genetic, network, by, the, master, regulatory, transcription, factor, 'GATA-1', and, its, coregulators])]). relacion([sujeto(['In', addition, to, the, crucial, 'GATA-1', coregulator, 'Friend', of, 'GATA-1', '(', 'FOG-1),', a, component, of, the, 'Mediator', 'complex,', 'Med1,', facilitates, 'GATA-1-dependent', transcription, at, select]), verbo([target]), complemento([genes, and, controls, erythropoiesis])]). relacion([sujeto(['It', is, not, known, to, what, extent, 'Med1', contributes, to, 'GATA-1', function, or, whether, 'Med1', controls, a, large, or, restricted, cohort, of, genes, that, are, not]), verbo([regulated]), complemento([by, 'GATA-1'])]). relacion([sujeto(['Using', a, genetic, complementation, assay, in, 'GATA-1-null', erythroid, 'cells,', we, demonstrate, that, 'Med1', and, another, 'Mediator', 'component,', 'Med25,']), verbo([regulate]), complemento([a, restricted, cohort, of, genes, that, are, predominantly, not, controlled, by, 'GATA-1'])]). relacion([sujeto(['Most', of, these, genes, were, not]), verbo([regulated]), complemento([by, 'Med1', in, fibroblasts])]). relacion([sujeto(['Loss-of-function', analyses, with, 'GATA-1-independent', 'Med1']), verbo([target]), complemento([genes, indicate, that, 'Rrad,', which, encodes, a, small, 'GTPase', induced, during, human, 'erythropoiesis,', conferred, erythroid, cell, survival])]). relacion([sujeto(['Children', with, 'Down', syndrome]), verbo([have]), complemento([an, increased, incidence, of, transient, abnormal, myelopoiesis, '(', 'TAM)', and, acute, megakaryoblastic, leukemia])]). relacion([sujeto(['The', majority, of, these, cases, harbor, somatic, mutations, in, the, 'GATA1', 'gene,', which, results, in, the]), verbo([loss]), complemento([of, 'full-length', 'GATA1'])]). relacion([sujeto(['We']), verbo([found]), complemento([through, genetic, studies, of, 106, patients, with, 'TAM', that, internally, deleted, 'GATA1', proteins, '(', 'GATA1-IDs)', lacking, amino, acid, residues, 77, -, 119, or, 74, -, 88, '(', created, by, splicing, 'mutations)', contributed, to, the, genesis, of, 'TAM', in, 6, patients])]). relacion([sujeto(['In', 'contrast,', 'GATA1-S']), verbo([promoted]), complemento([megakaryocyte, proliferation, more, profoundly, than, that, induced, by, 'GATA1', deficiency])]). relacion([sujeto(['These', results, indicate, that, the, internally, deleted, regions, play, important, roles, in, megakaryocyte, proliferation, and, that, perturbation, of, this, mechanism, is]), verbo([involved]), complemento([in, the, pathogenesis, of, 'TAM'])]). relacion([sujeto(['The', 'NXF', '(']), verbo([nuclear]), complemento([export, 'factor)', family, members, are, implicated, in, the, transport, of, mRNA, from, the, nucleus, to, the, cytoplasm])]). relacion([sujeto(['Recently,', some, members, of, the, 'NXF', family]), verbo([have]), complemento([been, reported, to, play, divergent, functional, 'roles,', such, as, 'post-transcriptional', 'regulation,', translational, 'control,', regulation, of, mRNA, stability, and, trafficking])]). relacion([sujeto(['In', the, present, 'study,', we]), verbo([found]), complemento([that, mouse, 'NXF3,', specifically, expressed, in, principal, cells, in, segment, 'II', of, the, caput, 'epididymis,', as, well, as, 'Sertoli', cells, in, the, mouse, 'testis,', was, required, to, mediate, 'TGF-β', '(', transforming, growth, factor, 'β)-induced', 'down-regulation', of, 'Tgfb3/TGF-β3', mRNA, expression, and, protein, secretion, in, 'Sertoli', cells])]). relacion([sujeto(['In', 'addition,', 'NXF3', was, also]), verbo([involved]), complemento([in, 'TGF-β-induced', transcriptional, regulation, of, other, genes, associated, with, 'Sertoli', cell, maturation, and, the, restructuring, of, the, 'Sertoli', cell, 'BTB', '(', 'blood-testis', 'barrier),', such, as, 'Gata1', '(', 'GATA-binding', protein, 1, ')', ',', 'Wt1', '(', 'Wilms\'s', tumour, homologue, 1, ')', ',', 'Cldn11', '(', 'claudin11)', and, 'Cdkn1a', '(', 'cyclin-dependent', kinase, inhibitor, 1, 'A', or, 'p21(Cip1))'])]). relacion([sujeto(['The', transcriptional, regulation, of, 'NXF3', was]), verbo([mediated]), complemento([through, physical, interaction, with, 'STRAP', '(', 'serine/threonine', kinase, 'receptor-associated', 'protein),', where, 'NXF3', inhibited, the, complex, formation, among, 'Smad7,', 'STRAP', and, activated, type, 'I', 'TGF-β', receptor])]). relacion([sujeto(['Taken', 'together,', our, data]), verbo([provide]), complemento([mechanistic, insights, into, the, roles, of, 'NXF3', in, 'TGF-β-mediated', expression, of, 'Tgfb3', and, other, genes])]). relacion([sujeto(['Dicer,', a, member, of, the, 'RNase', 'III', 'family,', is, the, key, enzyme]), verbo([required]), complemento([for, the, biogenesis, of, microRNAs, and, small, interfering, 'RNAs'])]). relacion([sujeto(['Recent', evidence, indicates, that, 'DICER1', expression, levels, vary, among, different, solid, tumors, and]), verbo([decreased]), complemento([or, increased, 'DICER1', expression, has, been, associated, with, aggressive, cancers])]). relacion([sujeto(['A', functional, assay, demonstrated, that, the, silencing, of, 'DICER1']), verbo([inhibited]), complemento([cell, proliferation, and, promoted, apoptosis, in, leukemia, cell, lines])]). relacion([sujeto(['These', data]), verbo([suggest]), complemento([that, 'DICER1', plays, an, important, role, in, 'AML', and, the, finding, that, the, upregulation, of, 'DICER1', is, induced, by, 'GATA1', may, provide, a, framework, for, the, understanding, of, differential, 'DICER1', expression, levels, in, multiple, types, of, cancer])]). relacion([sujeto(['As', an, important, step, towards, this, 'goal,', we]), verbo([report]), complemento([the, differentiation, of, human, embryonic, stem, cells, '(', 'hESCs)', towards, the, megakaryocyte, '(', 'Mk)', lineage, using, a, '\'', spin, embryoid, 'body\'', method, in, 'serum-free', differentiation, medium])]). relacion([sujeto(['Immunophenotypic', analyses, of, differentiating, hESC, identified, a, subpopulation, of, cells]), verbo([expressing]), complemento([high, levels, of, 'CD41a', that, expressed, other, markers, associated, with, the, 'Mk', 'lineage,', including, 'CD110,', 'CD42b', and, 'CD61'])]). relacion([sujeto(['Differentiated', 'Mk', cells, produced, 'platelet-like', particles, which]), verbo([expressed]), complemento(['CD42b', and, were, activated, by, 'ADP,', similar, to, platelets, generated, from, precursors, in, cord, blood])]). relacion([sujeto(['These', studies, were, complemented, by, real, time, 'PCR', analyses, showing, that, subsets, of, cells, enriched, for, 'CD41a⁺', 'Mk', precursors]), verbo([expressed]), complemento([high, levels, of, 'Mk', associated, genes, such, as, 'PF4', and, 'MPL'])]). relacion([sujeto(['Although', several, miRNAs]), verbo([regulate]), complemento([erythroid, 'differentiation,', how, the, key, erythroid, 'regulator,', 'GATA-1,', directly, orchestrates, differentiation, through, miRNA, pathways, remains, unclear])]). relacion([sujeto(['In', primary, human, 'CD34+', hematopoietic, progenitor, 'cells,', 'miR-23a']), verbo([increased]), complemento([in, a, 'GATA-1-dependent', manner, during, erythroid, differentiation])]). relacion([sujeto(['Furthermore,', a, protein, tyrosine, 'phosphatase,', 'SHP2,', was, identified, as, a, downstream]), verbo([target]), complemento([of, 'miR-23a', that, mediated, its, regulation, of, erythropoiesis])]). relacion([sujeto(['The', role, of, 'DNA', methylation, in, the, regulation, of, catabolic, genes, such, as, 'MMP13', and, 'IL1B,', which]), verbo([have]), complemento([sparse, 'CpG', 'islands,', is, poorly, understood, in, the, context, of, musculoskeletal, diseases])]). relacion([sujeto(['We']), verbo([report]), complemento([that, demethylation, of, specific, 'CpG', sites, at, -, 110, bp, and, -, 299, bp, of, the, proximal, 'MMP13', and, 'IL1B', 'promoters,', 'respectively,', detected, by, in, situ, methylation, analysis, of, chondrocytes, obtained, directly, from, human, 'cartilage,', strongly, correlated, with, higher, levels, of, gene, expression])]). relacion([sujeto(['Methylation', of, the, -, 110, bp, 'CpG', site, in, the, 'MMP13', promoter]), verbo([inhibited]), complemento([its, 'HIF-2α-driven', transactivation, and, decreased, 'HIF-2α', binding, to, the, 'MMP13', proximal, promoter, in, chromatin, immunoprecipitation, assays])]). relacion([sujeto(['However,', unlike, the, 'MMP13', 'promoter,', 'IL1B', was, not, susceptible, to, 'HIF-2α', 'transactivation,', indicating, that, the, -, 299, 'CpG', site, in, the, 'IL1B', promoter, must]), verbo([interact]), complemento([with, other, transcription, factors, to, modulate, 'IL1B', transcriptional, activity])]). relacion([sujeto(['Taken', 'together,', our, data]), verbo([reveal]), complemento([that, the, methylation, of, different, 'CpG', sites, in, the, proximal, promoters, of, the, human, 'MMP13', and, 'IL1B', genes, modulates, their, transcription, by, distinct, mechanisms])]). relacion([sujeto(['The', requirement, that, leukemic, 'Gata1', mutations, be, present, in, cells, harboring, trisomy, 21]), verbo([led]), complemento([to, the, discovery, that, overexpression, of, 'ERG', drives, aberrant, megakaryopoiesis])]). relacion([sujeto(['We', discovered, that, constitutive, 'AKT', signaling, is]), verbo([associated]), complemento([with, a, dramatic, increase, in, apoptosis, of, 'WT', megakaryocytes, '(', 'MKs),', but, that, overexpression, of, 'ERG', blocks, 'AKT-induced', death])]). relacion([sujeto(['We', further]), verbo([found]), complemento([that, 'Gata1', mutations, protect, 'MKs', from, activated, 'AKT-induced', apoptosis])]). relacion([sujeto(['As', a, 'consequence,', 'however,', the]), verbo([enhanced]), complemento([signaling, inhibits, differentiation, of, 'Gata1', 'mutant,', but, not, 'WT,', 'MKs'])]). relacion([sujeto(['Gata1', mutant, cells, that, overexpress, 'ERG', with, hyperactive, 'AKT', are, characterized, by, diminished, 'FOXO1/3a', expression, and, an]), verbo([increased]), complemento([dependency, on, the, 'c-Jun', pathway, similar, to, that, seen, in, acute, megakaryoblastic, leukemia, '(', 'AMKL)', cell, 'lines,', acute, myeloid, leukemia, '(', 'AML)', with, knockdown, of, 'FOXO3a,', or, 'AML', with, expression, of, myristoylated, 'Akt'])]). relacion([sujeto(['Additionally,', we]), verbo([found]), complemento([that, the, 'AKT', allosteric, inhibitor, 'MK2206', caused, reduced, cell, viability, and, proliferation, of, 'AMKL', cell, lines])]). relacion([sujeto(['The', contribution, of, aberrant, 'AKT', signaling, during, the, ontogeny, of, 'Down', 'syndrome-transient', myeloproliferative, 'disorder/AMKL', indicates, that, 'AKT', is, a, therapeutic]), verbo([target]), complemento([in, this, form, of, 'AML'])]). relacion([sujeto(['Mice', deficient, in, 'GATA-1', or, 'NF-E2,', transcription, factors]), verbo([required]), complemento([for, normal, megakaryocyte, '(', 'MK)', 'development,', have, increased, numbers, of, 'MKs,', reduced, numbers, of, 'platelets,', and, a, striking, high, bone, mass, phenotype])]). relacion([sujeto(['We']), verbo([found]), complemento([that, the, outer, geometry, of, the, mutant, bones, was, similar, to, 'controls,', but, that, both, mutants, had, a, striking, increase, in, total, bone, area, '(', up, to, a, 35, '%', 'increase)', and, trabecular, bone, area, '(', up, to, a, 19, '%', 'increase)'])]). relacion([sujeto(['Interestingly,', only, the, 'NF-E2', deficient, mice, had, a, significant]), verbo([increase]), complemento([in, cortical, bone, area, '(', 21, '%', ')', and, cortical, thickness, '(', 27, '%', ')', ',', which, is, consistent, with, the, increase, in, bone, mineral, density, '(', 'BMD)', seen, only, in, the, 'NF-E2', deficient, femurs])]). relacion([sujeto(['Both', mutant, femurs, exhibited, significant]), verbo([increases]), complemento([in, several, biomechanical, properties, including, peak, load, '(', up, to, a, 32, '%', 'increase)', and, stiffness, '(', up, to, a, 13, '%', 'increase)'])]). relacion([sujeto(['Although', none, of, the, parameters, measured, were, different, between, the, 'NF-E2', deficient, and, control, 'mice,', an]), verbo([increase]), complemento([in, calcium, '(', 21, '%', ')', and, an, increase, in, the, 'mineral/matrix', ratio, '(', 32, '%', ')', was, observed, in, 'GATA-1', deficient, mice])]). relacion([sujeto(['These', findings, appear, to, contradict, biomechanical, 'findings,']), verbo([suggesting]), complemento([the, need, for, further, research, into, the, mechanisms, by, which, 'GATA-1', and, 'NF-E2', deficiency, alter, the, material, properties, of, bone])]). relacion([sujeto(['We', hypothesized, that, a, unique, set, of, enhancers]), verbo([regulates]), complemento([gene, expression, in, human, erythroid, 'cells,', a, highly, specialized, cell, type, evolved, to, provide, adequate, amounts, of, oxygen, throughout, the, body])]). relacion([sujeto(['Consistent', with, their, predicted, function, as, candidate, 'enhancers,', there, was, statistically, significant, enrichment, of, p300, and, combinations, of, 'co-localizing', erythroid, transcription, factors, within, 1, -, 50, kb, of, the, transcriptional, start, site, '(', 'TSS)', of, genes, highly]), verbo([expressed]), complemento([in, erythroid, cells])]). relacion([sujeto(['Fourteen', candidate, 'enhancers,', representing, 10, genetic, 'loci,', mapped, to, sites]), verbo([associated]), complemento([with, biologically, relevant, erythroid, traits])]). relacion([sujeto(['Identification', of, enhancers, in, human, erythroid, cells, will, allow, a, better, understanding, of, erythroid, cell, 'development,', 'differentiation,', 'structure,', and, function, and]), verbo([provide]), complemento([insights, into, inherited, and, acquired, hematologic, disease])]). relacion([sujeto(['The', transcription, factor, 'Ikaros']), verbo([regulates]), complemento([the, development, of, hematopoietic, cells])]). relacion([sujeto(['Recently,']), verbo([loss]), complemento([of, 'Ikaros', was, associated, with, progression, of, myeloproliferative, neoplasms, to, acute, myeloid, leukemia, and, increasing, evidence, shows, that, 'Ikaros', is, also, critical, for, the, regulation, of, myeloid, development])]). relacion([sujeto(['Previous', studies, showed, that, 'Ikaros-deficient', mice]), verbo([have]), complemento([increased, 'megakaryopoiesis,', but, the, molecular, mechanism, of, this, phenomenon, remains, unknown])]). relacion([sujeto(['Here,', we, show, that, 'Ikaros', overexpression]), verbo([decreases]), complemento(['NOTCH-induced', megakaryocytic, 'specification,', and, represses, expression, of, several, megakaryocytic, genes, including, 'GATA-1', to, block, differentiation, and, terminal, maturation])]). relacion([sujeto(['We', also, demonstrate, that, 'Ikaros', expression, is, differentially]), verbo([regulated]), complemento([by, 'GATA-2', and, 'GATA-1', during, megakaryocytic, differentiation, and, reveal, that, the, combined, loss, of, 'Ikzf1', and, 'Gata1', leads, to, synthetic, lethality, in, vivo, associated, with, prominent, defects, in, erythroid, cells, and, an, expansion, of, megakaryocyte, progenitors])]). relacion([sujeto(['Cell', 'type-specific', transcription, factors]), verbo([regulate]), complemento([the, repertoire, of, genes, expressed, in, a, cell, and, thereby, determine, its, phenotype])]). relacion([sujeto(['Differentiation', of, hematopoietic, stem, cells, to, red, cells]), verbo([requires]), complemento([coordinated, expression, of, numerous, erythroid, genes, and, is, characterized, by, nuclear, condensation, and, extrusion, during, terminal, development])]). relacion([sujeto(['We', observed, widespread, epigenetic, differences, between, early, and, late, stages, of, erythropoiesis, with, progressive]), verbo([loss]), complemento([of, methylation, being, the, dominant, change, during, differentiation])]). relacion([sujeto(['Epigenetic', changes, at, transcription, factor]), verbo([binding]), complemento([sites, correlated, significantly, with, changes, in, gene, expression, and, were, enriched, for, binding, motifs, for, 'SCL,', 'MYB,', 'GATA,', and, other, factors, not, previously, implicated, in, erythropoiesis])]). relacion([sujeto(['Demethylation', at, gene, promoters, was]), verbo([associated]), complemento([with, increased, expression, of, 'genes,', whereas, epigenetic, changes, at, gene, bodies, correlated, inversely, with, gene, expression])]). relacion([sujeto(['Important', gene, networks, encoding, erythrocyte, membrane, 'proteins,', surface, 'receptors,', and, heme, synthesis, proteins, were]), verbo([found]), complemento([to, be, regulated, by, 'DNA', methylation])]). relacion([sujeto([1]), verbo([binding]), complemento([site, in, intron, 1, of, the, 'GATA1', gene])]). relacion([sujeto(['This', intronic, site, was]), verbo([found]), complemento([to, be, conserved, across, species, and, was, validated, to, be, a, novel, 'PU'])]). relacion([sujeto([1]), verbo([binding]), complemento([site, by, quantitative, 'ChIP', in, erythroid, cells])]). relacion([sujeto(['Altogether,', our, study]), verbo([provides]), complemento([a, comprehensive, analysis, of, methylomic, and, transcriptomic, changes, during, erythroid, differentiation, and, demonstrates, that, human, terminal, erythropoiesis, is, surprisingly, associated, with, hypomethylation, of, the, genome])]). relacion([sujeto(['Thus,', it, follows, that, the, 'converse,', alleviation, of, 'repression,', would, be, equally, 'effective,', since, the, net, result, would, be, the, 'same:', an]), verbo([increase]), complemento([in, fetal, hemoglobin])]). relacion([sujeto(['A', 'GATA-1-FOG-1-Mi2', repressor, complex, was, recently, demonstrated, to, be]), verbo([recruited]), complemento([to, the, -, 566, 'GATA', motif, of, the, '(', 'A)γ-globin', gene])]). relacion([sujeto(['In', 'addition,']), verbo([increased]), complemento([expression, of, '(', 'A)γ-globin', was, detected, in, adult, blood, from, 'β-YAC', transgenic, mice, containing, a, 'T>G', 'HPFH', point, mutation, at, the, -, 566, 'GATA', silencer, site])]). relacion([sujeto(['ChIP', experiments, demonstrated, that, 'GATA-1', is]), verbo([recruited]), complemento([to, this, silencer, at, day, 'E16,', followed, by, recruitment, of, 'FOG-1', and, 'Mi2', at, day, 'E17', in, 'wild-type', 'β-YAC', transgenic, mice])]). relacion([sujeto(['Our', data]), verbo([suggest]), complemento([that, a, temporal, repression, mechanism, is, operative, in, the, silencing, of, 'γ-globin', gene, expression, and, that, either, a, 'trans-acting', 'Mi2β', knockout, deletion, mutation, or, the, 'cis-acting', -, 566, '(', 'A)γ-globin', 'HPFH', point, mutation, disrupts, establishment, of, 'repression,', resulting, in, continued, 'γ-globin', gene, transcription, during, adult, definitive, erythropoiesis])]). relacion([sujeto([scube1, '(', signal, 'peptide-CUB', '(', complement, protein, 'C1r/C1s,', 'Uegf,', and, 'Bmp1)-EGF', 'domain-containing', protein, 1, ')', ',', the, founding, member, of, a, novel, secreted, and, cell, surface, 'SCUBE', protein, 'family,', is]), verbo([expressed]), complemento([predominantly, in, various, developing, tissues, in, mice])]). relacion([sujeto(['Whole-mount', in, situ, hybridization, revealed, that, zebrafish, scube1, mRNA, is, maternally]), verbo([expressed]), complemento([and, widely, distributed, during, early, embryonic, development])]). relacion([sujeto(['Knockdown', of, scube1, by, 'morpholino-oligonucleotide', 'down-regulated', the, expression, of, marker, genes]), verbo([associated]), complemento([with, early, primitive, hematopoietic, precursors, '(', 'scl)', and, erythroid, '(', gata1, and, 'hbbe1),', as, well, as, early, '(', pu])]). relacion([sujeto(['Our', results]), verbo([suggest]), complemento([that, scube1, is, critical, for, and, functions, at, the, top, of, the, regulatory, hierarchy, of, primitive, hematopoiesis, by, modulating, 'BMP', activity, during, zebrafish, embryogenesis])]). relacion([sujeto(['Abnormal', expression, of, microRNAs, '(', 'miRNAs)']), verbo([has]), complemento([been, implicated, in, carcinogenesis])]). relacion([sujeto(['Here', we]), verbo([report]), complemento([a, novel, 'BCR', '(', breakpoint, cluster, 'region)-ABL', '(', 'c-abl', oncogene, 1, ',', 'non-receptor', tyrosine, 'kinase)/GATA1/microRNA-138', '(', 'miR-138)', circuitry, in, chronic, myeloid, leukemia, '(', 'CML)'])]). relacion([sujeto(['The', tumor, suppressor, activity, of, 'miR-138', is, demonstrated, by, the, induction, of, cell, cycle]), verbo([arrest]), complemento([at, 'G0/G1,', inhibition, of, cell, proliferation, and, colony, forming, unit, 'granulocyte-macrophage', colony, formation, and, enhanced, 'imatinib-induced', apoptosis, in, 'K562', and, 'Ku812', cells, overexpressing, 'miR-138'])]). relacion([sujeto(['Moreover,', overexpression, of, 'miR-138']), verbo([led]), complemento([to, the, downregulation, of, 'BCR-ABL'])]). relacion([sujeto(['Based', on, luciferase, 'assay,', 'ABL', and, 'BCR-ABL', are, shown, to, be, the]), verbo([target]), complemento([genes, regulated, by, 'miR-138'])]). relacion([sujeto(['Furthermore,', 'miR-138']), verbo([binding]), complemento([to, 'ABL', was, shown, to, localize, to, the, coding, region, instead, of, 3, '\'', -, untranslated, regions, '(', 3, '\'', -, 'UTR)', of, 'ABL', mRNA])]). relacion([sujeto(['In', 'addition,', 'CCND3', is, another]), verbo([target]), complemento([of, 'miR-138,', which, represses, 'CCND3', expression, by, binding, to, its, 3, '\'', -, 'UTR'])]). relacion([sujeto(['Finally,', upregulation, of, 'miR-138', upon, imatinib, treatment, is]), verbo([associated]), complemento([with, the, enhancement, of, 'GATA1', 'activity,', which, binds, to, the, 'miR-138', promoter])]). relacion([sujeto(['miR-138', represses, expression, of, both, 'BCR-ABL', and, 'CCND3', via]), verbo([binding]), complemento([to, the, coding, region, and, 3, '\'', -, 'UTR,', respectively])]). relacion([sujeto(['miR-138', expression, is]), verbo([activated]), complemento([by, 'GATA1,', which, in, turn, is, repressed, by, 'BCR-ABL'])]). relacion([sujeto(['Histone', deacetylases, '(', 'HDACs)']), verbo([regulate]), complemento([multiple, developmental, processes, and, cellular, functions])]). relacion([sujeto(['However,', their, roles, in, blood, development]), verbo([have]), complemento([not, been, 'determined,', and, in, 'Xenopus', laevis, a, specific, function, for, 'HDACs', has, yet, to, be, identified])]). relacion([sujeto(['Here,', we, employed, the, class, 'I', selective, 'HDAC', 'inhibitor,', valproic, acid, '(', 'VPA),', to, show, that, 'HDAC', activity, is]), verbo([required]), complemento([for, primitive, hematopoiesis])]). relacion([sujeto(['These', effects, of, 'VPA', were, mimicked, by, 'Trichostatin', 'A', '(', 'TSA),', a, 'well-established', 'pan-HDAC', 'inhibitor,', but, not, by, 'valpromide,', which, is, structurally, similar, to, 'VPA', but, does, not]), verbo([inhibit]), complemento(['HDACs'])]). relacion([sujeto(['VPA', also]), verbo([caused]), complemento([a, 'marked,', 'dose-dependent', loss, of, primitive, erythroid, progenitors, in, mouse, yolk, sac, explants, at, clinically, relevant, concentrations])]). relacion([sujeto(['In', 'addition,', 'VPA', treatment]), verbo([inhibited]), complemento([erythropoietic, development, downstream, of, bmp4, and, gata1, in, 'Xenopus', ectodermal, explants])]). relacion([sujeto(['These', findings]), verbo([suggest]), complemento([an, important, role, for, class, 'I', 'HDACs', in, primitive, hematopoiesis])]). relacion([sujeto(['Our', work, also, demonstrates, that, specific, developmental, defects]), verbo([associated]), complemento([with, exposure, to, 'VPA,', a, significant, teratogen, in, 'humans,', arise, through, inhibition, of, class, 'I', 'HDACs'])]). relacion([sujeto(['To', test, what, percentages, of, 'ETO2-repressed', genes, could, be, direct]), verbo([target]), complemento([genes, of, 'GATA-1', in, 'K562', 'cells,', we, merged, the, microarray, results, with, 'ChIP-seq', profile, '(', 'n = 5,749),', demonstrating, that, 23.1, '%', of, 'ETO2-repressed', genes, contained, significant, 'GATA-1', in, their, loci])]). relacion([sujeto([1]), verbo([target]), complemento([genes, among, 'ETO2-repressed', genes])]). relacion([sujeto(['Quantitative', chromatin, immunoprecipitation, and, 'ETO2', knockdown, analyses, confirmed, that, 'ETO2', directly]), verbo([regulates]), complemento([globin, genes, in, 'K562', cells])]). relacion([sujeto(['Furthermore,', short, hairpin, 'RNA-mediated', knockdown, and, retroviral, 'vector-mediated', overexpression, of, 'ETO2', in, primary, erythroblasts]), verbo([suggested]), complemento([that, 'ETO2', significantly, represses, 'HBB,', 'HBA,', and, 'ALAS2', expression])]). relacion([sujeto(['In', 'summary,', 'ETO2']), verbo([regulates]), complemento(['GATA-1', target, genes, critical, for, erythroid, 'differentiation,', and, the, decrease, of, 'ETO2', levels, during, erythroid, differentiation, would, contribute, to, the, activation, of, these, targets])]). relacion([sujeto(['We', defined, a, 170, -, bp, region, within, the, promoter, and, showed, that, it, is]), verbo([involved]), complemento([in, repression, of, 'Ccna1', in, cultured, cells])]). relacion([sujeto(['Within', this, region, we, identified, known, 'cis-acting', transcription, factor]), verbo([binding]), complemento(['sequences,', including, an, 'Sp1-binding', site, and, two, 'GATA1-binding', sites])]). relacion([sujeto(['Neither', 'Sp1', nor, 'GATA1', is]), verbo([expressed]), complemento([in, pachytene, spermatocytes, and, later, stages, of, germ, cell, differentiation])]). relacion([sujeto(['Site-directed', mutagenesis, demonstrated, that, neither, factor, alone, was, sufficient, to, significantly, repress, expression, driven, by, the, 'Ccna1', 'promoter,', while, concurrent]), verbo([binding]), complemento([of, 'Sp1,', and, most, likely, 'GATA1', and, possibly, additional, factors, was, inhibitory])]). relacion([sujeto(['In', contrast, with, many, other, 'testis-specific', 'genes,', the, 'CpG', island, methylation, status, of, the, 'Ccna1', promoter, was, similar, among, various, tissues, 'examined,', irrespective, of, whether, 'Ccna1', was, transcriptionally, 'active,']), verbo([suggesting]), complemento([that, this, regulatory, mechanism, is, not, involved, in, the, restricted, expression, of, 'Ccna1'])]). relacion([sujeto(['By', using, the, 'GSE19650', affymetrix, microarray, data, accessible, from, 'Gene', 'Expression', 'Omnibus', '(', 'GEO)', 'database,', we, first, identified, the, differentially]), verbo([expressed]), complemento([genes, '(', 'DEGs)', between, 'IPMA', and, 'IPMC,', followed, by, the, 'protein-protein', interaction, and, 'single-nucleotide', polymorphism, '(', 'SNP)', analysis, of, the, 'DEGs'])]). relacion([sujeto(['Our', study, identified, thousands, of, 'DEGs', which]), verbo([involved]), complemento([regulation, of, cell, cycle, and, apoptosis, in, this, progression, from, 'IPMA', to, 'IPMC'])]). relacion([sujeto(['Protein-protein', interaction, network, construction]), verbo([found]), complemento([that, 'MYC,', 'IL6ST,', 'NR3C1,', 'CREBBP,', 'GATA1', and, 'LRP1', might, play, an, important, role, in, the, progression])]). relacion([sujeto(['In', 'conclusion,', our, data]), verbo([provide]), complemento([a, comprehensive, bioinformatics, analysis, of, genes, and, pathways, which, may, be, involved, in, the, progression, of, 'IPMN', from, 'IPMA', to, 'IPMC'])]). relacion([sujeto(['A', 'myofibroblast-like', 'CAF', cell, line]), verbo([expressing]), complemento([high, levels, of, smooth, muscle, actin, was, compared, to, normal, mammary, fibroblasts, before, and, after, induction])]). relacion([sujeto(['Induction', of, 'CAFs', by, exposure, of, normal, fibroblasts, to, conditioned, medium, from, 'MDA-MB-231', cells, resulted, in]), verbo([increased]), complemento([activation, of, reporters, for, 'HIF1,', several, 'STAT', 'TFs,', and, 'proliferation-related', 'TFs', such, as, 'AP1'])]). relacion([sujeto(['Myofibroblast-like', 'CAFs', and]), verbo([induced]), complemento([normal, mammary, fibroblasts, promoted, invasion, of, breast, cancer, cells, by, distinct, 'mechanisms,', consistent, with, their, distinct, patterns, of, 'TF', activation])]). relacion([sujeto(['The', 'TF', activity, profiles, of, 'CAF', subtypes]), verbo([provide]), complemento([an, overview, of, intracellular, signaling, associated, with, the, induction, of, a, 'pro-invasive', 'stroma,', and, provide, a, mechanistic, link, between, the, microenvironmental, stimuli, and, phenotypic, response])]). relacion([sujeto(['The', human, 'embryonic,', fetal, and, adult, 'β-like', globin, genes]), verbo([provide]), complemento([a, paradigm, for, 'tissue-', and, developmental, 'stage-specific', gene, regulation])]). relacion([sujeto(['The', fetal, 'γ-globin', gene, is]), verbo([expressed]), complemento([in, fetal, erythroid, cells, but, is, repressed, in, adult, erythroid, cells])]). relacion([sujeto(['We']), verbo([found]), complemento([that, the, proximal, 'γ-globin', promoter, complex, is, assembled, by, a, developmentally, 'regulated,', general, transcription, activator, 'NF-Y', bound, strongly, at, the, tandem, 'CCAAT', motifs, near, the, 'TATA', box])]). relacion([sujeto(['NF-Y']), verbo([recruits]), complemento([to, neighboring, 'DNA', motifs, the, developmentally, 'regulated,', erythroid, transcription, activator, 'GATA-2', and, general, repressor, 'BCL11A,', which, in, turn, recruit, erythroid, repressor, 'GATA-1', and, general, repressor, 'COUP-TFII', to, form, respectively, the, 'NF-Y/GATA-2', transcription, activator, hub, and, the, 'BCL11A/COUP-TFII/GATA-1', transcription, repressor, hub])]). relacion([sujeto(['Through', changes, in, their, levels, and, respective, interactions, with, the, 'co-activators', and, 'co-repressors', during, erythroid, 'development,', the, activator, and, the, repressor, hubs]), verbo([modulate]), complemento(['erythroid-', and, developmental, 'stage-specific', transcription, of, 'γ-globin', gene])]). relacion([sujeto(['Even', though, mutations, in, epigenetic, regulators, frequently, occur, in, myeloproliferative, 'neoplasms,', their, effects, on, the, epigenome]), verbo([have]), complemento([not, been, well, studied])]). relacion([sujeto(['Furthermore,', even, though, primary, myelofibrosis, '(', 'PMF)']), verbo([has]), complemento([a, markedly, worse, prognosis, than, essential, thrombocytosis, or, polycythemia, 'vera,', the, molecular, distinctions, between, these, subgroups, are, not, well, elucidated])]). relacion([sujeto(['The', differentially, methylated, genes, in, polycythemia, vera, and, essential, thrombocytosis, were]), verbo([involved]), complemento([predominantly, in, cell, signaling, pathways, and, were, enriched, for, binding, sites, of, 'GATA1', and, other, transcription, factors])]). relacion([sujeto(['In', 'contrast,', aberrantly, methylated, genes, in, 'PMF', were]), verbo([involved]), complemento([in, inflammatory, pathways, and, were, enriched, for, 'NF1,', 'LEF1,', and, other, transcription, factors])]). relacion([sujeto(['Within', the, 'PMF', 'subgroup,', cases, with, 'ASXL1', disruptions, formed, an, epigenetically, distinct, subgroup, with, relatively]), verbo([increased]), complemento([methylation])]). relacion([sujeto(['Cases', of, myeloproliferative, neoplasms, '(', 'MPN)', with, 'TET2', mutations, showed]), verbo([decreased]), complemento([levels, of, hydroxymethylation, and, distinct, set, of, hypermethylated, genes])]). relacion([sujeto(['These', results, show, epigenetic, differences, between, 'PMF', and, polycythemia, 'vera/essential', thrombocytosis, and]), verbo([reveal]), complemento([methylomic, signatures, of, 'ASXL1', and, 'TET2', mutations])]). relacion([sujeto(['The', 40, -, fold]), verbo([increase]), complemento([in, childhood, 'megakaryocyte-erythroid', and, 'B-cell', leukemia, in, 'Down', syndrome, implicates, trisomy, 21, '(', 'T21)', in, perturbing, fetal, hematopoiesis])]). relacion([sujeto(['Commensurately,', 'HSC', and, 'megakaryocyte-erythroid', progenitors, show, higher, 'clonogenicity,', with]), verbo([increased]), complemento(['megakaryocyte,', 'megakaryocyte-erythroid,', and, replatable, blast, colonies])]). relacion([sujeto(['Therefore,', 'T21', itself]), verbo([causes]), complemento([multiple, distinct, defects, in, 'FL', 'myelo-', and, lymphopoiesis])]). relacion([sujeto(['Acute', megakaryoblastic, leukemia, '(', 'AMKL)', is, a, heterogeneous, disease, generally]), verbo([associated]), complemento([with, poor, prognosis])]). relacion([sujeto(['Gene', expression, profiles, indicate, the, existence, of, distinct, molecular, 'subgroups,', and, several, genetic, alterations]), verbo([have]), complemento([been, characterized, in, the, past, 'years,', including, the, 't(1;22)(p13;q13)', and, the, trisomy, 21, associated, with, 'GATA1', mutations])]). relacion([sujeto(['In', this, 'study,', using, a, xenotransplantation, 'approach,', we]), verbo([have]), complemento([modeled, human, pediatric, 'AMKL', in, immunodeficient, mice])]). relacion([sujeto(['One', subgroup, of, patients, presented, with, 'MLL', or, 'NUP98', fusion, genes]), verbo([leading]), complemento([to, 'up-regulation', of, the, 'HOX', 'A', cluster, genes])]). relacion([sujeto(['A', novel, 'CBFA2T3-GLIS2', fusion, gene, resulting, from, a, cryptic, inversion, of, chromosome, 16, was, identified, in, another, subgroup, of, 31, '%', of, 'non-Down', syndrome, 'AMKL', and, strongly]), verbo([associated]), complemento([with, a, gene, expression, signature, of, 'Hedgehog', pathway, activation])]). relacion([sujeto(['These', molecular, data]), verbo([provide]), complemento([useful, markers, for, the, diagnosis, and, follow, up, of, patients])]). relacion([sujeto(['Glucocorticoid', action, in, neurons, is]), verbo([mediated]), complemento([by, glucocorticoid, receptors, '(', 'GR)', that, operate, as, transcription, factors, in, the, regulation, of, gene, expression, and, either, bind, directly, to, genomic, glucocorticoid, response, elements, '(', 'GREs)', or, indirectly, to, the, genome, via, interactions, with, bound, transcription, factors])]). relacion([sujeto(['The', objective, of, the, present, study, was, to, identify, 'genome-wide', glucocorticoid, receptor]), verbo([binding]), complemento([sites, in, neuronal, 'PC12', cells, using, 'Chromatin', 'ImmunoPrecipitation', combined, with, next, generation, sequencing, '(', 'ChIP-Seq)'])]). relacion([sujeto(['In', total, we, identified, 1183, genomic]), verbo([binding]), complemento([sites, of, 'GR,', the, majority, of, which, were, novel, and, not, identified, in, other, 'ChIP-Seq', studies, on, 'GR', binding])]). relacion([sujeto(['More', than, half, '(', 58, '%', ')', of, the]), verbo([binding]), complemento([sites, contained, a, 'GRE'])]). relacion([sujeto(['The', remaining, 42, '%', of, the, 'GBS', did, not, harbour, a, 'GRE', and, therefore, likely]), verbo([bind]), complemento(['GR', via, an, intermediate, transcription, factor, tethering, 'GR', to, the, 'DNA'])]). relacion([sujeto(['While', the, 'GRE-containing']), verbo([binding]), complemento([sites, were, more, often, located, nearby, genes, involved, in, general, cell, functions, and, processes, such, as, 'apoptosis,', cell, 'motion,', protein, dimerization, activity, and, vasculature, 'development,', the, binding, sites, without, a, 'GRE', were, located, nearby, genes, with, a, clear, role, in, neuronal, processes, such, as, neuron, projection, 'morphogenesis,', neuron, projection, 'regeneration,', synaptic, transmission, and, catecholamine, biosynthetic, process])]). relacion([sujeto(['A', closer, look, at, the, sequence, of, the, 'GR']), verbo([binding]), complemento([sites, revealed, the, presence, of, several, motifs, for, transcription, factors, that, are, highly, divergent, from, those, previously, linked, to, 'GR-signaling,', including, 'Gabpa,', 'Prrx2,', 'Zfp281,', 'Gata1', and, 'Zbtb3'])]). relacion([sujeto(['These', results]), verbo([provide]), complemento([an, exciting, first, global, view, into, neuronal, 'GR', targets, and, the, 'neuron-specific', modes, of, 'GR', action, and, potentially, contributes, to, our, understanding, of, glucocorticoid, action, in, the, brain])]). relacion([sujeto(['In', red, cell, 'development,', the, differentiation, program, directed, by, the, transcriptional, regulator, 'GATA1']), verbo([requires]), complemento([signaling, by, the, cytokine, 'erythropoietin,', but, the, mechanistic, basis, for, this, signaling, requirement, has, remained, unknown])]). relacion([sujeto(['Here', we, show, that, erythropoietin]), verbo([regulates]), complemento(['GATA1', through, protein, kinase, 'D', 'activation,', promoting, histone, deacetylase, 5, '(', 'HDAC5)', dissociation, from, 'GATA1,', and, subsequent, 'GATA1', acetylation])]). relacion([sujeto(['In', ex, vivo, 'studies,', 'HDAC5(-/-)', progenitors, display]), verbo([enhanced]), complemento([entry, into, and, passage, through, the, erythroid, 'lineage,', as, well, as, evidence, of, 'erythropoietin-independent', differentiation])]). relacion([sujeto(['These', results]), verbo([reveal]), complemento([a, molecular, pathway, that, contributes, to, cytokine, regulation, of, hematopoietic, differentiation, and, offer, a, potential, mechanism, for, fine, tuning, of, 'lineage-restricted', transcription, factors, by, 'lineage-specific', cytokines])]). relacion([sujeto(['During', 'erythropoiesis,', erythropoietin]), verbo([stimulates]), complemento([induction, of, erythroid, transcription, factors, that, activate, expression, of, erythroid, genes, including, the, erythropoietin, receptor, '(', 'EPO-R)', that, results, in, increased, sensitivity, to, erythropoietin])]). relacion([sujeto(['DNA']), verbo([binding]), complemento([of, the, basic, 'helix-loop-helix', transcription, 'factor,', 'TAL1/SCL,', is, required, for, normal, erythropoiesis])]). relacion([sujeto(['A', link, between, elevated, 'TAL1', and, excessive, erythrocytosis, is]), verbo([suggested]), complemento([by, erythroid, progenitor, cells, from, a, patient, that, exhibits, unusually, high, sensitivity, to, erythropoietin, with, concomitantly, elevated, 'TAL1', and, 'EPO-R', expression])]). relacion([sujeto(['We']), verbo([found]), complemento([that, 'TAL1', regulates, 'EPO-R', expression, mediated, via, three, conserved, 'E-box', binding, motifs, '(', 'CAGCTG)', in, the, 'EPO-R', 5, '\'', untranslated, transcribed, region])]). relacion([sujeto(['TAL1']), verbo([increases]), complemento([association, of, the, 'GATA-1·TAL1·LMO2·LDB1', transcription, activation, complex, to, the, region, that, includes, the, transcription, start, site, and, the, 5, '\'', 'GATA', and, 3, '\'', 'E-box', motifs, flanking, the, 'EPO-R', transcription, start, site, suggesting, that, 'TAL1', promotes, accessibility, of, this, region])]). relacion([sujeto(['Nucleosome', shifting]), verbo([has]), complemento([been, demonstrated, to, facilitate, 'TAL1', but, not, 'GATA-1', binding, to, regulate, target, gene, expression])]). relacion([sujeto(['Accordingly,', we, observed, that, with]), verbo([induced]), complemento([expression, of, 'EPO-R', in, hemotopoietic, progenitor, 'cells,', nucleosome, phasing, shifts, to, increase, the, linker, region, containing, the, 'EPO-R', transcription, start, site, and, 'TAL1', binds, to, the, flanking, 5, '\'', 'GATA', and, 3, '\'', 'E-box', regions, of, the, promoter])]). relacion([sujeto(['These', data]), verbo([suggest]), complemento([that, 'TAL1', binds, to, the, 'EPO-R', promoter, to, activate, 'EPO-R', expression, and, provides, a, potential, link, to, elevated, 'EPO-R', expression, leading, to, hypersensitivity, to, erythropoietin, and, the, resultant, excessive, erythrocytosis])]). relacion([sujeto(['Children', with, trisomy, 21]), verbo([have]), complemento([a, unique, predisposition, to, develop, a, megakaryoblastic, proliferative, disease, of, varying, severity, during, their, first, 3, &, 'nbsp;months', of, life])]). relacion([sujeto(['The', identification, that, 'GATA1', mutations, are, the, leukaemogenic, source, along, with, three, recently]), verbo([reported]), complemento([prospective, clinical, trials, now, provide, a, clearer, understanding, of, this, haematopoietic, disorder])]). relacion([sujeto(['The', transcription, factor, 'Foxp3']), verbo([participates]), complemento([dominantly, in, the, specification, and, function, of, 'Foxp3(+)CD4(+)', regulatory, 'T', cells, '(', 'T(reg)', 'cells)', but, is, neither, strictly, necessary, nor, sufficient, to, determine, the, characteristic, 'T(reg)', cell, signature])]). relacion([sujeto(['Enforced', expression, of, 'Helios', or, 'Xbp1', elicited, distinct, 'signatures,', but, 'Eos,', 'IRF4,', 'Satb1,', 'Lef1', and, 'GATA-1', elicited, exactly, the, same, 'outcome,']), verbo([acting]), complemento([in, synergy, with, 'Foxp3', to, activate, expression, of, most, of, the, 'T(reg)', cell, 'signature,', including, key, transcription, 'factors,', and, enhancing, occupancy, by, 'Foxp3', at, its, genomic, targets])]). relacion([sujeto(['Growth', 'Factor', 'Independence', '(', 'Gfi)', transcription, factors, play, essential, roles, in, 'hematopoiesis,', differentially]), verbo([activating]), complemento([and, repressing, transcriptional, programs, required, for, hematopoietic, 'stem/progenitor', cell, '(', 'HSPC)', development, and, lineage, specification])]). relacion([sujeto(['In', 'mammals,', 'Gfi1a']), verbo([regulates]), complemento([hematopoietic, stem, cells, '(', 'HSC),', myeloid, and, lymphoid, 'populations,', while, its, 'paralog,', 'Gfi1b,', regulates, 'HSC,', megakaryocyte, and, erythroid, development])]). relacion([sujeto(['Here,', we]), verbo([report]), complemento([the, isolation, and, characterization, of, an, additional, hematopoietic, gfi, 'factor,', gfi1b])]). relacion([sujeto(['We', show, that, gfi1aa, and, gfi1b, are]), verbo([expressed]), complemento([in, the, primitive, and, definitive, sites, of, hematopoiesis, in, zebrafish])]). relacion([sujeto(['Our', functional, analyses, demonstrate, that, gfi1aa, and, gfi1b]), verbo([have]), complemento([distinct, roles, in, regulating, primitive, and, definitive, hematopoietic, 'progenitors,', respectively])]). relacion([sujeto(['Conversely,']), verbo([loss]), complemento([of, gfi1b, silences, 'runx-1,', 'c-myb,', ikaros, and, 'cd41,', indicating, that, gfi1b, is, required, for, definitive, hematopoiesis])]). relacion([sujeto(['Transcription', factors]), verbo([bind]), complemento([in, a, combinatorial, fashion, to, specify, the, 'on-and-off', states, of, 'genes;', the, ensemble, of, these, binding, events, forms, a, regulatory, 'network,', constituting, the, wiring, diagram, for, a, cell])]). relacion([sujeto(['To', examine, the, principles, of, the, human, transcriptional, regulatory, 'network,', we, determined, the, genomic]), verbo([binding]), complemento([information, of, 119, 'transcription-related', factors, in, over, 450, distinct, experiments])]). relacion([sujeto(['We']), verbo([found]), complemento([the, 'combinatorial,', 'co-association', of, transcription, factors, to, be, highly, context, 'specific:', distinct, combinations, of, factors, bind, at, specific, genomic, locations])]). relacion([sujeto(['In', 'particular,', there, are, significant, differences, in, the]), verbo([binding]), complemento([proximal, and, distal, to, genes])]). relacion([sujeto(['We', organized, all, the, transcription, factor]), verbo([binding]), complemento([into, a, hierarchy, and, integrated, it, with, other, genomic, information, '(', for, 'example,', microRNA, 'regulation),', forming, a, dense, 'meta-network'])]). relacion([sujeto(['Factors', at, different, levels]), verbo([have]), complemento([different, 'properties;', for, 'instance,', 'top-level', transcription, factors, more, strongly, influence, expression, and, 'middle-level', ones, 'co-regulate', targets, to, mitigate, 'information-flow', bottlenecks])]). relacion([sujeto(['Finally,', more, connected, network, components, are, under, stronger, selection, and, exhibit, a, greater, degree, of, 'allele-specific', activity, '(', that, 'is,', differential]), verbo([binding]), complemento([to, the, two, parental, 'alleles)'])]). relacion([sujeto(['This', review, describes, the, genetics, of, unusual, blood, group, 'phenotypes,', particularly, those, with, altered, expression, of, 'Lutheran', 'antigens,', and, how, this, area, of, study]), verbo([has]), complemento([informed, our, understanding, of, erythropoiesis, in, general, and, haemoglobin, switching, in, particular])]). relacion([sujeto(['Mutations', in, erythroid, transcription, factors, 'GATA1', '(', 'GATA1']), verbo([binding]), complemento([protein, 1, ')', and, 'KLF1', '(', 'Kruppel-like', factor, 1, ')', cause, benign, and, disease, phenotypes, in, humans, '[', 'X-linked', 'Lu(a-b-)', 'phenotype,', 'In(Lu)', blood, group, 'phenotype,', hereditary, persistence, of, foetal, 'haemoglobin,', borderline, 'HbA(2),', and, congenital, dyserythropoietic, anaemia, '(', 'CDA)]'])]). relacion([sujeto(['Subsequently,', numerous, additional, mutations]), verbo([have]), complemento([been, 'described,', one, of, which, causes, a, rare, form, of, 'CDA'])]). relacion([sujeto(['The', apparent, sensitivity, of, the, 'Lutheran', glycoprotein, to, alterations, in, 'GATA1', and, 'KLF1', activity]), verbo([suggest]), complemento([that, it, could, be, a, useful, biomarker, of, erythroid, transcription, factor, mutation])]). relacion([sujeto(['In', 'mammals,', hematopoietic, homeostasis, is]), verbo([maintained]), complemento([by, a, 'fine-tuned', balance, among, the, 'self-renewal,', 'proliferation,', differentiation, and, survival, of, hematopoietic, stem, cells, and, their, progenies])]). relacion([sujeto(['GATA1', is, a, transcription, factor, that, comprehensively]), verbo([regulates]), complemento([the, genes, that, are, important, for, the, development, of, erythroid, and, megakaryocytic, cells])]). relacion([sujeto(['In', 'particular,', the, somatic, mutation, of, the, 'GATA1', 'gene,', which]), verbo([leads]), complemento([to, the, production, of, 'N-terminally', truncated, 'GATA1,', contributes, to, the, genesis, of, transient, myeloproliferative, disorder, and, acute, megakaryoblastic, leukemia, in, infants, with, 'Down', syndrome])]). relacion([sujeto(['Similarly,', a, mutation, in, the, 'GATA1', regulatory, region, that, reduces, 'GATA1', expression, is]), verbo([involved]), complemento([in, the, onset, of, erythroid, leukemia, in, mice])]). relacion([sujeto(['In', both, 'cases,', the, accumulation, of, immature, progenitor, cells]), verbo([caused]), complemento([by, 'GATA1', dysregulation, underlies, the, pathogenesis, of, the, leukemia])]). relacion([sujeto(['This', review]), verbo([provides]), complemento([a, summary, of, 'multi-step', leukemogenesis, with, a, focus, on, 'GATA1', dysfunction])]). relacion([sujeto(['Human', erytholeukemia, 'K562', cells, are]), verbo([induced]), complemento([to, differentiate, along, the, erythroid, lineage, by, a, variety, of, chemical, 'compounds,', including, 'hemin,', sodium, butyrate, and, 1, -, 'β-d-arabinofuranosylcytosine'])]). relacion([sujeto(['We']), verbo([have]), complemento([investigated, the, induction, of, erythroid, differentiation, of, 'K562', cells, by, glutamine, depletion])]). relacion([sujeto(['This', induction, was, dependent, on, the, temporally, marked]), verbo([decrease]), complemento([of, intracellular, level, of, 'glutathione,', followed, by, the, marked, activation, of, p38MAPK, and, 'SAPK/JNK,', but, not, 'ERK'])]). relacion([sujeto(['The', transcriptional, activity, of, 'β-globin', gene, 'promoter-reporter', was, markedly]), verbo([enhanced]), complemento([by, these, 'treatments,', indicating, that, glutamine, deficiency, in, combination, with, sodium, butyrate, treatment, gives, high, efficiency, of, 'chemical-induced', differentiation, in, the, hematopoiesis, process])]). relacion([sujeto(['Severe', congenital, anemia, '(', hemoglobin, 72, 'g/L),', thrombocytopenia, '(', 42, '×G/L)', and, profound, platelet, dysfunction]), verbo([led]), complemento([a, stem, cell, defect, to, be, suspected])]). relacion([sujeto(['Because', the, interaction, between, 'omega-3', fatty, acids, and, mast, cells]), verbo([has]), complemento([remained, largely, unknown, in, 'allergies,', we, investigated, whether, 'omega-3', fatty, acids, affect, the, activation, of, mast, cells, by, examining, 'Th2-associated', cytokine, production, and, possible, molecular, mechanisms])]). relacion([sujeto(['Alpha-linolenic', acid, and, its, metabolites, including, eicosapentaenoic, acid, and, decosahexaenoic, acid]), verbo([induced]), complemento([a, dramatic, decrease, in, the, production, of, interleukin, '(', 'IL)-4,', 'IL-5', and, 'IL-13', in, a, 'dose-dependent', 'manner,', as, well, as, mRNA, expression, of, their, 'genes,', in, activated, 'MC/9', mast, cells, and, bone, 'marrow-derived', mast, cells])]). relacion([sujeto(['Nuclear', expression, of, 'GATA']), verbo([binding]), complemento(['protein-1', '(', 'GATA-1)', and, 'GATA', binding, 'protein-2', '(', 'GATA-2),', essential, transcription, factors, for, mast, cell, 'activation,', was, also, greatly, suppressed])]). relacion([sujeto(['In', 'P815', mast, 'cells,', which, do, not]), verbo([express]), complemento(['GATA-1,', the, suppressive, effects, on, cytokines, were, abolished])]). relacion([sujeto(['On', the, 'contrary,', 'omega-3', fatty, acids, had, less, significant, effects, on, 'IL-4', and, 'IL-5', and, resulted, in, a, slight]), verbo([decrease]), complemento([in, 'IL-13', production, in, 'EL-4', 'T', cells])]). relacion([sujeto(['The', number, of, cells]), verbo([expressing]), complemento(['CD117(+)', and, 'FcεRIα(+)', was, greatly, decreased, and, 'GATA-1', expression, in, the, cells, was, also, diminished])]). relacion([sujeto(['Taken', 'together,', 'omega-3', fatty, acids, might]), verbo([target]), complemento([mast, cells, to, a, greater, extent, than, 'T', cells, to, suppress, 'Th2', cytokine, expression, by, inhibiting, 'GATAs', for, alleviation, of, allergic, disease])]). relacion([sujeto(['Tissue-specific', transcription, patterns, are, preserved, throughout, cell, divisions, to]), verbo([maintain]), complemento([lineage, fidelity])]). relacion([sujeto(['Live-cell', imaging, revealed, that, a, fraction, of, 'GATA1', is]), verbo([retained]), complemento([focally, within, mitotic, chromatin])]). relacion([sujeto(['The', 'GATA1', coregulators, 'FOG1', and, 'TAL1', dissociate, from, mitotic, 'chromatin,']), verbo([suggesting]), complemento([that, 'GATA1', functions, as, platform, for, their, postmitotic, recruitment])]). relacion([sujeto(['Mitotic', 'GATA1']), verbo([target]), complemento([genes, tend, to, reactivate, more, rapidly, upon, entry, into, 'G1', than, genes, from, which, 'GATA1', dissociates])]). relacion([sujeto(['Mitosis-specific', destruction, of, 'GATA1', delays, reactivation, selectively, of, genes, that]), verbo([retain]), complemento(['GATA1', during, mitosis])]). relacion([sujeto(['These', studies]), verbo([suggest]), complemento([a, requirement, of, mitotic, &, 'quot;bookmarking"', by, 'GATA1', for, the, faithful, propagation, of, 'cell-type-specific', transcription, programs, through, cell, division])]). relacion([sujeto(['The', joint, application, of, clinical, and, genetic, investigation, to, patients, with, inherited, 'thrombocytopenias,', as, well, as, the, availability, of, new, methods, for, studying, 'megakaryopoiesis,']), verbo([has]), complemento([greatly, expanded, the, knowledge, of, these, disorders, in, the, last, few, years, with, regard, to, their, 'etiology,', pathogenesis, and, clinical, aspects])]). relacion([sujeto(['In', 'particular,', new, diseases]), verbo([have]), complemento([been, 'described,', as, deriving, from, mutations, in, the, genes, 'FLNA,', 'TUBB1,', 'ITGA2/ITGB3,', 'ANKRD26,', 'CYCS,', and, 'ABCG5', or, 'ABCG8'])]). relacion([sujeto(['Moreover,', forms, previously, considered, separate, entities, were]), verbo([found]), complemento([to, be, different, clinical, aspects, of, a, single, disease])]). relacion([sujeto(['For', 'instance,', identification, of, 'MYH9', as, the, gene, whose, mutations]), verbo([cause]), complemento([the, 'May-Hegglin', anomaly, led, to, the, recognition, that, 'Sebastian', platelet, 'syndrome,', 'Epstein', 'syndrome,', and, 'Fechtner', syndrome, derive, from, mutations, of, the, same, gene, and, describe, overlapping, disorders])]). relacion([sujeto(['Despite', these, 'advances,', knowledge, of, hereditary, thrombocytopenias, is, still, far, from, satisfactory, because, for, approximately, half, of, the, patients, it, is, not, possible, to, formulate, a, definite, diagnosis, in, that, their, illnesses]), verbo([has]), complemento([not, yet, been, described])]). relacion([sujeto(['In', this, 'review,', we]), verbo([provide]), complemento([a, systematic, description, of, hereditary, thrombocytopenias, as, we, know, them, 'today,', giving, special, attention, to, genetic, aspects])]). relacion([sujeto(['Previous', imaging, and, postmortem, studies]), verbo([have]), complemento([reported, a, lower, brain, volume, and, a, smaller, size, and, density, of, neurons, in, the, dorsolateral, prefrontal, cortex, '(', 'dlPFC)', of, subjects, with, major, depressive, disorder, '(', 'MDD)'])]). relacion([sujeto(['These', findings]), verbo([suggest]), complemento([that, synapse, number, and, function, are, decreased, in, the, dlPFC, of, patients, with, 'MDD'])]). relacion([sujeto(['However,', there]), verbo([has]), complemento([been, no, direct, evidence, reported, for, synapse, loss, in, 'MDD,', and, the, gene, expression, alterations, underlying, these, effects, have, not, been, identified])]). relacion([sujeto(['Here', we, use, microarray, gene, profiling, and, electron, microscopic, stereology, to]), verbo([reveal]), complemento([lower, expression, of, 'synaptic-function–related', genes, '(', 'CALM2,', 'SYN1,', 'RAB3A,', 'RAB4B', and, 'TUBB4)', in, the, dlPFC, of, subjects, with, 'MDD', and, a, corresponding, lower, number, of, synapses])]). relacion([sujeto(['We', also, identify, a, transcriptional, 'repressor,', 'GATA1,', expression, of, which, is, higher, in, 'MDD', and, 'that,', when]), verbo([expressed]), complemento([in, 'PFC', 'neurons,', is, sufficient, to, decrease, the, expression, of, 'synapse-related', 'genes,', cause, loss, of, dendritic, spines, and, 'dendrites,', and, produce, depressive, behavior, in, rat, models, of, depression])]). relacion([sujeto(['A', role, for, 'GATA1', as, a, cell, proliferation, regulator]), verbo([has]), complemento([been, 'proposed,', as, some, of, its, bona, fide, targets, comprise, global, 'regulators,', such, as, 'c-KIT', or, 'c-MYC,', or, cell, cycle, 'factors,', i])]). relacion([sujeto(['In', this, 'study,', we, describe, that, 'GATA1', directly]), verbo([regulates]), complemento([the, expression, of, replication, licensing, factor, 'CDC6'])]). relacion([sujeto(['Using', reporter, 'transactivation,', electrophoretic, mobility, shift, and, chromatin, immunoprecipitation, 'assays,', we, show, that, 'GATA1']), verbo([stimulates]), complemento(['CDC6', transcription, by, binding, to, a, canonical, binding, site, located, within, a, 166, bp, enhancer, region, upstream, 'CDC6', promoter])]). relacion([sujeto(['This', evolutionary]), verbo([conserved]), complemento(['GATA', binding, site, conforms, to, recently, described, chromatin, occupancy, 'rules,', i])]). relacion([sujeto(['We', also]), verbo([found]), complemento([adjacent, conserved, binding, sites, for, ubiquitously, expressed, transcription, factor, 'CP2,', needed, for, 'GATA', activity, on, 'CDC6', enhancer])]). relacion([sujeto(['Our', results, add, to, the, growing, evidence, for, 'GATA1']), verbo([acting]), complemento([as, a, direct, transcriptional, regulator, of, the, cell, cycle, 'machinery,', thus, linking, cell, proliferation, control, and, specific, gene, expression, programs, during, lineage, differentiation])]). relacion([sujeto(['Studies']), verbo([have]), complemento([shown, that, monocytes, are, hyporesponsive, and, that, dendritic, cells, '(', 'DCs)', are, depleted, in, burn, patients])]). relacion([sujeto(['We']), verbo([have]), complemento([recently, shown, in, a, mouse, model, that, burn, injury, alters, the, transcriptional, regulation, in, bone, marrow, progenitors, and, inhibits, 'myeloid-derived', 'DC', '(', 'mDC)', production])]). relacion([sujeto(['In', the, present, 'study,', using, human, burn, patient, peripheral, blood, mononuclear, 'cells,', we]), verbo([have]), complemento([shown, an, overexpression, of, 'MafB', with, a, corresponding, reduction, in, peripheral, blood, mononuclear, 'cell-derived', mDCs])]). relacion([sujeto(['The', mDC, fraction, was, identified, by, the, expression, of, human, leukocyte, antigen, '(', 'HLA)-DR+CD11c+,', and, we]), verbo([found]), complemento([a, significant, reduction, in, 'HLA-DR+', leukocytes, for, up, to, 4, weeks, postburn])]). relacion([sujeto(['MafB', gene, silencing, improved, the, differentiation, potential, of, 'CD14+', cells, into, 'mDCs,']), verbo([increasing]), complemento([the, percentage, of, mDCs, by, &, 'gt;75%'])]). relacion([sujeto(['Furthermore,', 'GATA-1+', and, 'HLA-DR+', mDCs, were]), verbo([increased]), complemento([following, 'MafB', silencing])]). relacion([sujeto(['Signaling', from, 'IL1RL1/ST2']), verbo([induced]), complemento([by, 'IL-33', binding, was, recently, identified, as, a, modulator, of, the, 'Th2', response])]). relacion([sujeto(['The']), verbo([target]), complemento([cells, for, 'IL-33', are, restricted, in, some, hematopoietic, 'lineages,', including, mast, 'cells,', 'basophils,', 'eosinophils,', 'Th2', 'cells,', natural, killer, 'cells,', and, dendritic, cells])]). relacion([sujeto(['Reporter', assays]), verbo([suggested]), complemento([that, two, 'GATA', motifs, just, upstream, of, the, transcription, start, site, in, the, 'ST2', promoter, are, critical, for, transcriptional, activity])]). relacion([sujeto(['These', two, 'GATA', motifs, possess, the, capacity, to]), verbo([bind]), complemento(['GATA1', and, 'GATA2', in, 'EMSA'])]). relacion([sujeto(['ChIP', assay, showed, that, 'GATA2,', but, not, 'GATA1,']), verbo([bound]), complemento([to, the, 'ST2', promoter, in, 'LAD2', cells, and, that, histone, 'H3', at, the, 'ST2', promoter, was, acetylated, in, 'LAD2', 'cells,', whereas, binding, of, 'GATA1', and, 'GATA2', to, the, 'ST2', promoter, was, detected, in, 'KU812', cells])]). relacion([sujeto(['Although', 'GATA1', is, one, of, the, most, extensively, studied, haematopoietic, transcription, factors, little, is, currently, known, about, the, physiological, functions, of, its, naturally, occurring, isoforms, 'GATA1s', and, 'GATA1FL', in, 'humans-particularly', whether, the, isoforms]), verbo([have]), complemento([distinct, roles, in, different, lineages, and, whether, they, have, 'non-redundant', roles, in, haematopoietic, differentiation])]). relacion([sujeto(['As', well, as, being, of, general, interest, to, understanding, of, 'haematopoiesis,', 'GATA1', isoform, biology, is, important, for, children, with, 'Down', syndrome]), verbo([associated]), complemento([acute, megakaryoblastic, leukaemia, '(', 'DS-AMKL)', where, 'GATA1FL', mutations, are, an, essential, driver, for, disease, pathogenesis])]). relacion([sujeto(['K562', cells]), verbo([expressing]), complemento(['GATA1s', or, 'GATA1FL', transgenes, were, used, to, model, the, effects, of, the, two, isoforms, on, in, vitro, haematopoietic, differentiation])]). relacion([sujeto(['We']), verbo([found]), complemento([no, evidence, for, lineage, specific, use, of, 'GATA1', 'isoforms;', however, 'GATA1s', 'transcripts,', but, not, 'GATA1FL', 'transcripts,', are, 'down-regulated', during, in, vitro, induction, of, terminal, megakaryocytic, and, erythroid, differentiation, in, the, cell, line, 'K562'])]). relacion([sujeto(['In', 'addition,', transgenic, 'K562-GATA1s', and, 'K562-GATA1FL', cells]), verbo([have]), complemento([distinct, gene, expression, profiles, both, in, steady, state, and, during, terminal, erythroid, 'differentiation,', with, 'GATA1s', expression, characterised, by, lack, of, repression, of, 'MYB,', 'CCND2', and, 'SKI'])]). relacion([sujeto(['In', addition, our, data]), verbo([suggest]), complemento([that, 'SKI', may, be, a, potential, therapeutic, target, for, the, treatment, of, children, with, 'DS-AMKL'])]). relacion([sujeto(['KLF1', '(', formerly, known, as, 'EKLF)']), verbo([regulates]), complemento([the, development, of, erythroid, cells, from, 'bi-potent', progenitor, cells, via, the, transcriptional, activation, of, a, diverse, set, of, genes])]). relacion([sujeto(['We']), verbo([have]), complemento([recently, described, the, full, repertoire, of, 'KLF1', binding, sites, in, vivo, by, performing, 'KLF1', 'ChIP-seq', in, primary, erythroid, tissue, '(', 'E14'])]). relacion([sujeto(['This']), verbo([has]), complemento([revealed, novel, target, genes, not, previously, obtainable, by, traditional, microarray, 'technology,', and, provided, novel, insights, into, the, function, of, 'KLF1', as, a, transcriptional, activator])]). relacion([sujeto(['We', define, a, 'cis-regulatory', module]), verbo([bound]), complemento([by, 'KLF1,', 'GATA1,', 'TAL1,', and, 'EP300', that, coordinates, a, core, set, of, erythroid, genes])]). relacion([sujeto(['We', also, describe, a, novel, set, of, 'erythroid-specific', promoters, that, drive, 'high-level', expression, of, otherwise, ubiquitously]), verbo([expressed]), complemento([genes, in, erythroid, cells])]). relacion([sujeto(['Our', study]), verbo([has]), complemento([identified, two, novel, lncRNAs, that, are, dynamically, expressed, during, erythroid, 'differentiation,', and, discovered, a, role, for, 'KLF1', in, directing, apoptotic, gene, expression, to, drive, the, terminal, stages, of, erythroid, maturation])]). relacion([sujeto(['Chloroplasts', develop, from, proplastids, in, a, process, that]), verbo([requires]), complemento([the, interplay, of, nuclear, and, chloroplast, 'genomes,', but, key, steps, in, this, developmental, process, have, yet, to, be, elucidated])]). relacion([sujeto(['Here,', we, show, that, the, 'nucleus-localized', transcription, factors, 'GATA', 'NITRATE-INDUCIBLE', 'CARBON-METABOLISM-INVOLVED', '(', 'GNC)', and, 'CYTOKININ-RESPONSIVE', 'GATA1', '(', 'CGA1)']), verbo([regulate]), complemento([chloroplast, 'development,', 'growth,', and, division, in, 'Arabidopsis', '(', 'Arabidopsis', 'thaliana)'])]). relacion([sujeto(['GNC', and, 'CGA1', are, highly]), verbo([expressed]), complemento([in, green, 'tissues,', and, the, phytohormone, cytokinin, regulates, their, expression])]). relacion([sujeto(['Ectopic', overexpression, of, either, 'GNC', or, 'CGA1']), verbo([promotes]), complemento([chloroplast, biogenesis, in, hypocotyl, cortex, and, root, pericycle, 'cells,', based, on, increases, in, the, number, and, size, of, the, 'chloroplasts,', and, also, results, in, expanded, zones, of, chloroplast, production, into, the, epidermis, of, hypocotyls, and, cotyledons, and, into, the, cortex, of, roots])]). relacion([sujeto(['Ectopic', overexpression, also]), verbo([promotes]), complemento([the, development, of, etioplasts, from, proplastids, in, 'dark-grown', 'seedlings,', subsequently, enhancing, the, deetiolation, process])]). relacion([sujeto(['Inducible', expression, of, 'GNC', demonstrates, that, 'GNC-mediated', chloroplast, biogenesis, can, be]), verbo([regulated]), complemento(['postembryonically,', notably, so, for, chloroplast, production, in, cotyledon, epidermal, cells])]). relacion([sujeto(['Analysis', of, the, gnc, cga1, 'loss-of-function', and, overexpression, lines, supports, a, role, for, these, transcription, factors, in]), verbo([regulating]), complemento([the, effects, of, cytokinin, on, chloroplast, division])]). relacion([sujeto(['These', data, support, a, model, in, which, 'GNC', and, 'CGA1', serve, as, two, of, the, master, transcriptional, regulators, of, chloroplast, 'biogenesis,']), verbo([acting]), complemento([downstream, of, cytokinin, and, mediating, the, development, of, chloroplasts, from, proplastids, and, enhancing, chloroplast, growth, and, division, in, specific, tissues])]). relacion([sujeto(['Deficiency', of, the, transcription, factor, 'MafB,', which, is, normally]), verbo([expressed]), complemento([in, 'macrophages,', can, underlie, cellular, dysfunction, associated, with, a, range, of, autoimmune, diseases, and, arteriosclerosis])]). relacion([sujeto(['MafB']), verbo([has]), complemento([important, roles, in, cell, differentiation, and, regulation, of, target, gene, 'expression;', 'however,', the, mechanisms, of, this, regulation, and, the, identities, of, other, transcription, factors, with, which, 'MafB', interacts, remain, uncertain])]). relacion([sujeto(['Bioinformatics', methods]), verbo([provide]), complemento([a, valuable, approach, for, elucidating, the, nature, of, these, interactions, with, transcriptional, regulatory, elements, from, a, large, number, of, 'DNA', sequences])]). relacion([sujeto(['Here,', the, directional, relationships, among, several, functional, motifs, were, evaluated, using, the, 'Log-linear', 'Graphical', 'Model', '(', 'LGM)', after, extraction, and, search, for, evolutionarily]), verbo([conserved]), complemento([motifs])]). relacion([sujeto(['GATA-1', motifs, and, 'MafB', motifs, could]), verbo([regulate]), complemento([expression, of, these, genes, in, both, a, negative, and, positive, 'manner,', respectively])]). relacion([sujeto(['GATA-1', was]), verbo([found]), complemento([to, inhibit, the, activity, of, the, 'C1qa', promoter, with, the, 'GATA-1', motifs, and, 'MafB', motifs])]). relacion([sujeto(['These', observations]), verbo([suggest]), complemento([that, both, the, 'GATA-1', motifs, and, 'MafB', motifs, are, important, for, lineage, specific, expression, of, 'C1qa'])]). relacion([sujeto(['In', 'addition,', these, findings, show, that, analysis, of, combinations, of, evolutionarily]), verbo([conserved]), complemento([motifs, can, be, successfully, used, to, identify, patterns, of, gene, regulation])]). relacion([sujeto(['RUNX1']), verbo([has]), complemento([been, shown, to, be, part, of, a, large, transcription, factor, 'complex,', together, with, 'LDB1,', 'GATA1,', 'TAL1,', and, 'ETO2', '(', 'N'])]). relacion([sujeto(['We', used, a, tagging, strategy, to, show, that, 'RUNX1']), verbo([interacts]), complemento([with, two, novel, protein, 'partners,', 'LSD1', and, 'MYEF2,', in, erythroid, cells])]). relacion([sujeto(['MYEF2', is]), verbo([bound]), complemento([in, undifferentiated, cells, and, is, lost, upon, 'differentiation,', whereas, 'LSD1', is, bound, in, differentiated, cells])]). relacion([sujeto(['Chromatin', immunoprecipitation, followed, by, sequencing, '(', 'ChIP-seq)', and, microarray, expression, analysis, were, used, to, show, that, 'RUNX1']), verbo([binds]), complemento([approximately, 9, ',', 0, target, sites, in, erythroid, cells, and, is, primarily, active, in, the, undifferentiated, state])]). relacion([sujeto(['Functional', analysis, shows, that, a, subset, of, the]), verbo([target]), complemento([genes, is, suppressed, by, 'RUNX1', via, the, newly, identified, partner, 'MYEF2'])]). relacion([sujeto(['Using', mouse, erythroleukemia, 'cells,', we]), verbo([found]), complemento([that, the, 'RNA', interference, '(', 'RNAi)-mediated', depletion, of, 'HES1', enhances, erythroid, cell, 'differentiation,', suggesting, that, this, protein, opposes, terminal, erythroid, differentiation])]). relacion([sujeto(['This', is, also, supported, by, the]), verbo([decreased]), complemento([primary, erythroid, cell, differentiation, upon, 'HES1', upregulation, in, 'Ikaros-deficient', mice])]). relacion([sujeto(['A', comprehensive, analysis]), verbo([led]), complemento([us, to, determine, that, 'Ikaros', favors, 'Hes1', repression, in, erythroid, cells, by, facilitating, recruitment, of, the, master, regulator, of, erythropoiesis, 'GATA-1', alongside, 'FOG-1,', which, mediates, 'Hes1', repression])]). relacion([sujeto(['GATA-1', is, then, necessary, for, the, chromatin]), verbo([binding]), complemento([of, the, 'NuRD', remodeling, complex, 'ATPase', 'MI-2,', the, transcription, factor, 'GFI1B,', and, the, histone, 'H3K27', methyltransferase, 'EZH2', along, with, 'Polycomb', repressive, complex, 2])]). relacion([sujeto(['We', show, that, 'EZH2', is]), verbo([required]), complemento([for, the, transient, repression, of, 'Hes1', in, erythroid, cells])]). relacion([sujeto(['In', 'aggregate,', our, results, describe, a, mechanism, whereby, 'GATA-1', utilizes, 'Ikaros', and, 'Polycomb', repressive, complex, 2, to]), verbo([promote]), complemento(['Hes1', repression, as, an, important, step, in, erythroid, cell, differentiation])]). relacion([sujeto(['Myeloid', leukemia, in, 'Down', syndrome, '(', 'ML-DS)', is]), verbo([associated]), complemento([with, good, response, to, chemotherapy, and, favorable, prognosis])]). relacion([sujeto(['Because', little, research]), verbo([has]), complemento([been, focused, on, 'refractory/relapsed', '(', 'R/R)', 'cases,', we, conducted, a, retrospective, analysis, for, 'R/R', 'ML-DS'])]). relacion([sujeto(['Thirteen', of, the, 26, patients, achieved, complete, remission, with, various, kinds, of, reinduction, 'chemotherapies;', 2, of, 8, survived, without, further, recurrence, after, receiving, allogeneic, hematopoietic, stem, cell, 'transplantation,', and, 4, of, 5]), verbo([maintained]), complemento([complete, remissions, with, chemotherapy, alone])]). relacion([sujeto(['Treatment', failures, mostly, were]), verbo([associated]), complemento([with, disease, progression, rather, than, 'treatment-related', toxicities])]). relacion([sujeto(['GATA-1', and, its, cofactor, 'FOG-1', are]), verbo([required]), complemento([for, the, differentiation, of, erythrocytes, and, megakaryocytes])]). relacion([sujeto(['In', 'contrast,', mast, cell, development]), verbo([requires]), complemento(['GATA-1', and, the, absence, of, 'FOG-1'])]). relacion([sujeto(['Through', 'genome-wide', comparison, of, the, chromatin, occupancy, of, 'GATA-1', and, a, naturally, occurring, mutant, that, cannot]), verbo([bind]), complemento(['FOG-1', '(', 'GATA-1(V205G)),', we, reveal, that, 'FOG-1', intricately, regulates, the, chromatin, occupancy, of, 'GATA-1'])]). relacion([sujeto(['We', identified, 'GATA1-selective', and, 'GATA-1(V205G)-selective']), verbo([binding]), complemento([sites, and, show, that, 'GATA-1,', in, the, absence, of, 'FOG-1,', occupies, 'GATA-1(V205G)-selective', 'sites,', but, not, 'GATA1-selective', sites])]). relacion([sujeto(['By', integrating, 'ChIP-seq', and, gene, expression, 'data,', we, discovered, that, 'GATA-1(V205G)']), verbo([binds]), complemento([and, activates, mast, 'cell-specific', genes, via, 'GATA-1(V205G)-selective', sites])]). relacion([sujeto(['We', further, show, that, exogenous, expression, of, 'FOG-1', in, mast, cells]), verbo([leads]), complemento([to, displacement, of, 'GATA-1', from, mast, 'cell-specific', genes, and, causes, their, downregulation])]). relacion([sujeto(['Together', these, findings, establish, a, mechanism, of, gene, regulation, whereby, a, 'non-DNA']), verbo([binding]), complemento([cofactor, directly, modulates, the, occupancy, of, a, transcription, factor, to, control, lineage, specification])]). relacion([sujeto(['Anemia', is, a, hematologic, disorder, with]), verbo([decreased]), complemento([number, of, erythrocytes])]). relacion([sujeto(['Erythropoiesis,', the, process, by, which, red, blood, cells, 'differentiate,', are]), verbo([conserved]), complemento([in, 'humans,', mice, and, zebrafish])]). relacion([sujeto(['Ginger', '(', 'Zingiber', 'officinale)']), verbo([has]), complemento([been, widely, used, in, traditional, 'medicine;', 'however,', to, date, there, is, no, scientific, research, documenting, the, potential, of, ginger, to, stimulate, hematopoiesis])]). relacion([sujeto(['We', confirmed, that, ginger, and, 10, -, gingerol]), verbo([promote]), complemento([the, expression, of, gata1, in, erythroid, cells, and, increase, the, expression, of, hematopoietic, progenitor, markers, cmyb, and, scl])]). relacion([sujeto(['We', also, demonstrated, that, ginger, and, 10, -, gingerol, can]), verbo([promote]), complemento([the, hematopoietic, recovery, from, acute, hemolytic, anemia, in, 'zebrafish,', by, quantifying, the, number, of, circulating, erythroid, cells, in, the, dorsal, aorta, using, video, microscopy])]). relacion([sujeto(['We']), verbo([found]), complemento([that, ginger, and, 10, -, gingerol, treatment, during, gastrulation, results, in, an, increase, of, bmp2b, and, bmp7a, 'expression,', and, their, downstream, 'effectors,', gata2, and, eve1])]). relacion([sujeto(['At', later, stages, ginger, and, 10, -, gingerol, can]), verbo([induce]), complemento(['bmp2b/7a,', 'cmyb,', scl, and, lmo2, expression, in, the, caudal, hematopoietic, tissue, area])]). relacion([sujeto(['We', further, confirmed, that, 'Bmp/Smad', pathway]), verbo([mediates]), complemento([this, hematopoiesis, promoting, effect, of, ginger, by, using, the, 'Bmp-activated', 'Bmp', type, 'I', receptor, kinase, inhibitors, 'dorsomorphin,', 'LND193189', and, 'DMH1'])]). relacion([sujeto(['Our', study]), verbo([provides]), complemento([a, strong, foundation, to, further, evaluate, the, molecular, mechanism, of, ginger, and, its, bioactive, components, during, hematopoiesis, and, to, investigate, their, effects, in, adults])]). relacion([sujeto(['Our', results, will]), verbo([provide]), complemento([the, basis, for, future, research, into, the, effect, of, ginger, during, mammalian, hematopoiesis, to, develop, novel, erythropoiesis, promoting, agents])]). relacion([sujeto(['It', is, also, the, most, frequent]), verbo([target]), complemento([of, genetic, alterations, in, human, leukemia])]). relacion([sujeto(['Here,', we]), verbo([report]), complemento([that, 'RUNX1', is, phosphorylated, by, 'Src', family, kinases, '(', 'SFKs)', and, that, this, occurs, on, multiple, tyrosine, residues, located, within, its, negative, regulatory, 'DNA-binding', and, autoinhibitory, domains])]). relacion([sujeto(['We', also, demonstrate, that, the, nonreceptor, tyrosine, phosphatase, 'Shp2']), verbo([binds]), complemento([directly, to, 'RUNX1', and, contributes, to, its, dephosphorylation])]). relacion([sujeto(['Last,', we, show, that, 'RUNX1', tyrosine, phosphorylation, correlates, with, reduced, 'GATA1', and]), verbo([enhanced]), complemento(['SWI/SNF', interactions])]). relacion([sujeto(['Increasing', evidence, points, to, endoglin, '(', 'Eng),', an, accessory, receptor, for, the, transforming, growth, 'factor-β', superfamily, commonly]), verbo([associated]), complemento([with, the, endothelial, 'lineage,', as, an, important, regulator, of, the, hematopoietic, lineage])]). relacion([sujeto(['We']), verbo([have]), complemento([shown, that, lack, of, 'Eng', results, in, reduced, numbers, of, primitive, erythroid, colonies, as, well, as, downregulation, of, key, hematopoietic, genes])]). relacion([sujeto(['Our', results, demonstrate, that, induction, of, 'Eng', during, embryoid, body, differentiation]), verbo([leads]), complemento([to, a, significant, increase, in, the, frequency, of, hematopoietic, 'progenitors,', in, 'particular,', the, erythroid, 'lineage,', which, correlated, with, upregulation, of, 'Scl,', 'Gata1,', 'Runx1,', and, embryonic, globin])]). relacion([sujeto(['Eng-induced']), verbo([enhanced]), complemento([erythroid, activity, was, accompanied, by, high, levels, of, 'Smad1', phosphorylation])]). relacion([sujeto(['Among', the, 'BMPs,', 'BMP4', is, well, known, for, its, role, in, hematopoietic, specification, from, mesoderm, by]), verbo([promoting]), complemento([expression, of, several, hematopoietic, 'genes,', including, 'Scl'])]). relacion([sujeto(['Scl', expression, in, 'Eng-deficient', embryonic, stem, cells, resulted, in]), verbo([increased]), complemento([erythroid, 'colony-forming', activity, and, upregulation, of, 'Gata1', and, 'Gata2,', positioning, 'Eng', upstream, of, 'Scl'])]). relacion([sujeto(['Taken', 'together,', these, findings, support, the, premise, that, 'Eng']), verbo([modulates]), complemento([the, hematopoietic, transcriptional, 'network,', most, likely, through, regulation, of, 'BMP4', signaling])]). relacion([sujeto(['These', findings]), verbo([provide]), complemento([insight, into, the, pathogenesis, of, 'DBA,', showing, that, the, reduction, in, erythropoiesis, associated, with, the, disease, can, arise, from, causes, other, than, defects, in, ribosomal, protein, genes])]). relacion([sujeto(['They', identified, two, unrelated, pedigrees, in, which, the, disease, is]), verbo([associated]), complemento([with, mutations, in, 'GATA1,', which, encodes, an, essential, hematopoietic, transcription, factor, with, no, known, mechanistic, links, to, ribosomes])]). relacion([sujeto(['The', progression, of, 'CML', is]), verbo([associated]), complemento([with, genomic, instability])]). relacion([sujeto(['Etoposide-induced', 'DNA', damage, was, chosen, and, the, concentration, and, time, of, exposure, determined, such, that, apoptosis, was, not]), verbo([associated]), complemento([with, the, study])]). relacion([sujeto(['Hemogen', is, a, transcriptional]), verbo([target]), complemento([of, 'HOXB4', and, 'GATA1,', two, transcription, factors, involved, in, haemopoietic, 'development,', and, is, overexpressed, in, acute, myeloid, leukaemia])]). relacion([sujeto(['Furthermore', we]), verbo([found]), complemento([that, multiple, protein, phosphorylation, changes, mediated, by, 'BCR/ABL', were, connected, to, the, increased, activation, of, 'NFκB,', a, key, survival, transcription, 'factor,', after, etoposide, exposure])]). relacion([sujeto(['In', erythroid, 'cells,', the, locus, control, region, '(', 'LCR)', and, 'β-globin', promoter, form, a, chromatin, loop, that]), verbo([requires]), complemento([transcription, factor, 'GATA1', and, the, associated, molecule, 'Ldb1'])]). relacion([sujeto(['Remarkably,']), verbo([targeting]), complemento(['Ldb1', or, only, its, 'self-association', domain, to, the, 'β-globin', promoter, substantially, activated, 'β-globin', transcription, in, the, absence, of, 'GATA1'])]). relacion([sujeto(['Promoter-tethered', 'Ldb1']), verbo([interacted]), complemento([with, endogenous, 'Ldb1', complexes, at, the, 'LCR', to, form, a, chromatin, 'loop,', causing, recruitment, and, phosphorylation, of, 'RNA', polymerase, 'II'])]). relacion([sujeto(['We']), verbo([have]), complemento([investigated, the, role, of, erythroid, transcription, factors, mRNA, expression, in, patients, with, acute, myeloid, leukemia, '(', 'AML)', in, the, context, of, cytogenetic, and, other, prognostic, molecular, 'markers,', such, as, 'FMS-like', 'Tyrosine', 'Kinase', 3, '(', 'FLT3),', 'Nucleophosmin', 1, '(', 'NPM1),', and, 'CCAAT/enhance-binding', protein, α, '(', 'CEBPA)', mutations])]). relacion([sujeto(['We', evaluated, 'GATA']), verbo([binding]), complemento([protein, 1, '(', 'GATA1),', 'GATA', binding, protein, 2, '(', 'GATA2),', 'EKLF', and, 'Myeloproliferative', 'Leukemia', virus, oncogen, homology, '(', 'cMPL)', gene, mRNA, expression, in, the, bone, marrow, of, 65, 'AML', patients, at, 'diagnosis,', and, assessed, any, correlation, with, 'NPM1,', 'FLT3', and, 'CEBPA', mutations])]). relacion([sujeto(['EKLF-positive', 'AML', was]), verbo([associated]), complemento([with, lower, 'WBC', in, peripheral, blood, '(', 'P', =, 0.049, ')', ',', a, higher, percentage, of, erythroblasts, in, bone, marrow, '(', p, =, 0.057, ')', ',', and, secondary, 'AMLs', '(', 'P', =, 0.036, ')'])]). relacion([sujeto(['Patients']), verbo([expressing]), complemento(['EKLF', had, longer, 'Overall', 'Survival', '(', 'OS)', and, 'Event', 'Free', 'Survival', '(', 'EFS)', than, those, patients, not, expressing, 'EKLF', '(', median, 'OS', was, 35.61, months, and, 19.31, 'months,', 'respectively,', 'P', =, 0.0241, ;, median, 'EFS', was, 19.8, months, and, 8.03, 'months,', 'respectively,', 'P', =, 0.014, ')'])]). relacion([sujeto(['In', 'conclusion,', we]), verbo([have]), complemento([validated, 'EKLF', mRNA, expression, as, an, independent, predictor, of, outcome, in, 'AML,', and, its, expression, is, not, associated, with, 'FLT3-ITD', and, 'NPM1', mutations])]). relacion([sujeto(['It']), verbo([has]), complemento([been, reported, that, the, phosphatidylinositol, 3, -, kinase, '(', 'PI3K)-AKT', signaling, pathway, regulates, erythropoietin, '(', 'EPO)-induced', 'survival,', 'proliferation,', and, maturation, of, early, erythroid, progenitors])]). relacion([sujeto(['Erythroid', cell, proliferation, and, survival]), verbo([have]), complemento([also, been, related, to, activation, of, the, 'JAK-STAT', pathway])]). relacion([sujeto(['The', goal, of, this, study, was, to, observe, the, function, of, 'EPO', activation, of, 'JAK-STAT', and, 'PI3K/AKT', pathways, in, the, development, of, erythroid, progenitors, from, hematopoietic, 'CD34+', progenitor, 'cells,', as, well, as, to, distinguish, early, 'EPO']), verbo([target]), complemento([genes, in, human, erythroid, progenitors, during, ontogeny])]). relacion([sujeto(['We']), verbo([have]), complemento([used, microarray, analysis, to, examine, 'JAK-STAT', and, 'PI3K/AKT', related, 'genes,', as, well, as, broad, gene, expression, modulation, in, these, human, erythroid, progenitor, cells])]). relacion([sujeto(['In', microarray, 'studies,', a, total, of, 1755, genes, were]), verbo([expressed]), complemento([in, fetal, 'liver,', 3844, in, cord, 'blood,', 1770, in, adult, bone, 'marrow,', and, 1325, genes, in, peripheral, 'blood-derived', erythroid, progenitor, cells])]). relacion([sujeto(['In', 'addition,', some, 'JAK-STAT', pathway, related, genes, are, differentially]), verbo([expressed]), complemento([only, in, some, stages, of, ontogeny, '(', 'STATs,', 'GRB2,', 'CREBB)'])]). relacion([sujeto(['Beside', the, continuously, upregulated, '(', 'AKT1,', 'PPP2CA,', 'CHUK,', 'NFKB1)', and, downregulated, '(', 'FOXO1,', 'PDPK1,', 'PIK3CG)', genes, in, the, 'PI3K-AKT', signaling, 'pathway,', we, also, observed, intermittently]), verbo([regulated]), complemento([gene, expression, '(', 'NFKBIA,', 'YWHAH)'])]). relacion([sujeto(['This', broad, overview, of, gene, expression, in, erythropoiesis, revealed, transcription, factors, differentially]), verbo([expressed]), complemento([in, some, stages, of, ontogenesis])]). relacion([sujeto(['Finally,', our, results, show, that, 'EPO-mediated', proliferation, and, survival, of, erythroid, progenitors, occurs, mainly, through, modulation, of, 'JAK-STAT', pathway]), verbo([associated]), complemento(['STATs,', 'GRB2', and, 'PIK3', 'genes,', as, well, as, 'AKT', 'pathway-coupled', 'NFKBIA', and, 'YWHAH', genes])]). relacion([sujeto(['We']), verbo([have]), complemento([analyzed, publicly, available, 'K562', 'Hi-C', 'data,', which, enable, 'genome-wide', unbiased, capturing, of, chromatin, 'interactions,', using, a, 'Mixture', 'Poisson', 'Regression', 'Model', and, a, 'power-law', decay, background, to, define, a, highly, specific, set, of, interacting, genomic, regions])]). relacion([sujeto(['We', classified, 12, different, sets, '(', 'clusters)', of]), verbo([interacting]), complemento([loci, that, can, be, distinguished, by, their, chromatin, modifications, and, which, can, be, categorized, into, two, types, of, chromatin, linkages])]). relacion([sujeto(['As', 'expected,', many, of, the, transcription, factors, show]), verbo([binding]), complemento([patterns, specific, to, clusters, composed, of, interacting, loci, that, encompass, promoters, or, enhancers])]). relacion([sujeto(['However,', cluster, 9, ',', which, is, distinguished, by, marks, of, open, chromatin, but, not, by, active, enhancer, or, promoter, 'marks,', was, not]), verbo([bound]), complemento([by, most, transcription, factors, but, was, highly, enriched, for, three, transcription, factors, '(', 'GATA1,', 'GATA2', and, 'c-Jun)', and, three, chromatin, modifiers, '(', 'BRG1,', 'INI1', and, 'SIRT6)'])]). relacion([sujeto(['We']), verbo([found]), complemento([that, knockdown, of, the, 'GATA', factors, not, only, alters, the, expression, of, genes, having, a, nearby, bound, 'GATA', but, also, affects, expression, of, genes, in, interacting, loci])]). relacion([sujeto(['Our', 'work,', in, combination, with, previous, studies, linking, regulation, by, 'GATA', factors, with, 'c-Jun', and, 'BRG1,']), verbo([provides]), complemento(['genome-wide', evidence, that, 'Hi-C', data, identify, sets, of, biologically, relevant, interacting, loci])]). relacion([sujeto(['Possible', explanations, for, these, outcomes, include, immunologic, response, to, sepsis, by, a, 'leukemia-specific', 'T-cell', response, or, the]), verbo([release]), complemento([of, various, 'cytokines,', such, as, tumor, necrosis, factor, and, 'interleukin-2,', during, infections])]). relacion([sujeto(['Natural', killer, and, cytotoxic, 'T', cells, transfused, with, blood, products, might]), verbo([have]), complemento([also, triggered, an, immune, response])]). relacion([sujeto(['Carbonic', anhydrase, 1, '(', 'Car1),', an, early, specific, marker, of, the, erythroid, 'differentiation,']), verbo([has]), complemento([been, used, to, distinguish, fetal, and, adult, erythroid, cells, since, its, production, closely, follows, the, 'γ-', to, 'β-globin', 'transition,', but, the, molecular, mechanism, underlying, transcriptional, regulation, of, 'Car1', is, unclear])]). relacion([sujeto(['Here,', we, show, that, 'Car1', mRNA]), verbo([decreases]), complemento([significantly, when, erythroid, differentiation, is, induced, in, 'MEL', cells])]). relacion([sujeto(['The', 'Ldb1', protein, complex, including, 'GATA1/SCL/LMO2']), verbo([binds]), complemento([to, the, 'Car1', promoter, in, uninduced, cells, and, reduced, enrichment, of, the, complex, during, differentiation, correlates, with, loss, of, 'Car1', expression])]). relacion([sujeto(['Knockdown', of, 'Ldb1', results, in, a, reduction, of, 'Ser2']), verbo([phosphorylated]), complemento(['RNA', 'Pol', 'II', and, 'Cdk9', at, the, 'Car1', promoter, 'region,', suggesting, that, 'Ldb1', is, required, for, recruitment, of, 'Pol', 'II', as, well, as, the, transcription, regulator, 'P-TEFb', to, enhance, elongation, of, 'Car1', transcripts])]). relacion([sujeto(['Taken', 'together,', these, data, show, that, 'Ldb1', forms, a, regulatory, complex, to]), verbo([maintain]), complemento(['Car1', expression, in, erythroid, cells])]). relacion([sujeto(['The', goal, of, the, study, was, to, assess, whether, pulsatile, atheroprone, shear, stress]), verbo([modulates]), complemento([the, expression, of, transient, receptor, potential, '(', 'TRP)', 'channels,', 'TRPC3,', 'TRPC6,', 'TRPM7,', and, 'TRPV1', 'mRNA,', in, human, umbilical, vascular, endothelial, cells])]). relacion([sujeto(['Exposure', of, cultured, vascular, endothelial, cells, to, defined, shear, 'stress,', producing, a, constant, laminar, flow, '(', generating, a, shear, stress, of, 6, 'dyne/cm(2)),', laminar, pulsatile, atheroprotective, flow, '(', with, a, mean, shear, stress, of, 20, 'dyne/cm(2)),', or, laminar, atheroprone, bidirectional, flow, '(', with, a, mean, shear, stress, of, 0, 'dyne/cm(2))', differentially]), verbo([induced]), complemento(['TRPC6', and, 'TRPV1', mRNA, as, measured, by, quantitative, 'real-time', 'RT-PCR', and, normalized, to, 'GAPDH', expression])]). relacion([sujeto(['Thereby,', 'TRPC6', and, 'TRPV1', mRNA, expressions, were, significantly]), verbo([increased]), complemento([after, 24, hours, of, exposure, to, an, atheroprone, flow, profile, compared, with, an, atheroprotective, flow, profile])]). relacion([sujeto(['No-flow', and, atheroprone, flow, conditions, are, equally, characterized, by, an]), verbo([increase]), complemento([in, the, expression, of, tumor, necrosis, 'factor-α;', 'however,', 'inflammation-associated', endothelial, cell, reactions, may, be, further, aggravated, at, atheroprone, flow, conditions, by, the, increase, of, 'TRPV1', and, 'TRPC6,', as, observed, in, our, study])]). relacion([sujeto(['Hyperthermia', treatment]), verbo([has]), complemento([at, times, been, associated, with, increased, platelet, levels, in, humans])]). relacion([sujeto(['The', heat, shock, protein, 'HSP70,', which, can, be]), verbo([induced]), complemento([by, hyperthermia, in, megakaryocytes, and, 'erythrocytes,', was, recently, shown, to, protect, 'GATA-1', from, degradation, and, to, be, required, for, erythroid, differentiation])]). relacion([sujeto(['Cell', growth, and, erythroid, differentiation]), verbo([increased]), complemento([dramatically, in, cord, blood, 'CD34(+)', cell, cultures, incubated, under, 'MH'])]). relacion([sujeto(['Erythroid', maturation, was, also, strongly, 'promoted,', which, resulted, in, an]), verbo([increased]), complemento([proportion, of, hemoglobinized, and, enucleated, erythroids])]). relacion([sujeto(['The', molecular, basis, for, this, potent, synergy, appears, to, originate, from, the, capacity, of, 'MH', to]), verbo([increase]), complemento([the, basal, activation, of, several, signaling, molecules, downstream, of, the, 'EPO', receptor, and, the, transcriptional, activity, of, 'GATA-1'])]). relacion([sujeto(['Moreover,', the, potent, impact, of, 'MH', on, erythroid, development, was]), verbo([found]), complemento([be, dependent, on, increased, intracellular, levels, of, reactive, oxygen, species])]). relacion([sujeto(['Thus,', 'fever-like', temperatures, can]), verbo([promote]), complemento([the, differentiation, of, progenitors, along, the, erythroid, lineage, and, accelerate, their, maturation, through, normal, regulatory, circuitry])]). relacion([sujeto(['Nfil3,', a, transcription, factor, that]), verbo([has]), complemento([an, array, of, functions, in, immune, 'cells,', has, been, described, as, key, regulator, of, 'CD8α(+)', dendritic, cell, and, natural, killer, cell, development, in, mice])]). relacion([sujeto(['In', this]), verbo([report]), complemento([we, show, that, 'Nfil3', is, enriched, in, the, myeloid, compartment, of, adult, zebrafish, including, eosinophils])]). relacion([sujeto(['Using', mpx, and, 'fms-fluorescent', transgenic, fish, we]), verbo([found]), complemento([that, all, myeloid, cell, 'lineages,', and, in, particular, 'macrophages,', had, reduced, numbers, at, 4, days, 'post-fertilization'])]). relacion([sujeto(['Collectively,', these, results, describe, a]), verbo([conserved]), complemento([expression, pattern, of, 'Nfil3', in, evolutionarily, divergent, species, and, indicate, that, 'Nfil3', is, central, to, myeloid, lineage, commitment])]). relacion([sujeto(['Transcription', factor, 'GATA1']), verbo([regulates]), complemento([the, expression, of, a, cluster, of, genes, important, for, hematopoietic, cell, differentiation, toward, erythroid, and, megakaryocytic, lineages])]). relacion([sujeto(['Three', functional, domains]), verbo([have]), complemento([been, identified, in, 'GATA1,', a, transactivation, domain, located, in, the, 'N', terminus, '(', 'N-TAD)', and, two, zinc, finger, domains, located, in, the, middle, of, the, molecule])]). relacion([sujeto(['Although', 'N-TAD', is, known, as, a, solitary, transactivation, domain, for, 'GATA1,', clinical, observations, in, 'Down', syndrome, leukemia]), verbo([suggest]), complemento([that, there, may, be, additional, transactivation, domains])]). relacion([sujeto(['In', this, 'study,', we]), verbo([found]), complemento([in, reporter, 'co-transfection', assays, that, transactivation, activity, of, 'GATA1', was, markedly, reduced, by, deletion, of, the, 'C-terminal', 95, amino, acids, without, significant, attenuation, of, the, 'DNA', binding, activity, or, 'self-association', potential])]). relacion([sujeto(['We', therefore, generated, transgenic, mouse, lines, that]), verbo([expressed]), complemento(['GATA1', lacking, the, 'C-terminal', region, '(', 'GATA1-ΔCT)'])]). relacion([sujeto(['When', we, crossed, these, transgenic, mouse, lines, to, the, 'Gata1-deficient', 'mouse,', we]), verbo([found]), complemento([that, the, 'GATA1-ΔCT', transgene, rescued, 'Gata1-deficient', mice, from, embryonic, lethality])]). relacion([sujeto(['Distinct', sets, of]), verbo([target]), complemento([genes, were, affected, in, the, embryos, rescued, by, 'GATA1-ΔCT', and, 'GATA1-ΔNT'])]). relacion([sujeto(['We', also]), verbo([found]), complemento([attenuated, 'GATA1', function, in, cell, cycle, control, of, immature, megakaryocytes, in, both, lines, of, rescued, embryos])]). relacion([sujeto(['These', results, thus, demonstrate, that, 'GATA1']), verbo([has]), complemento([two, independent, transactivation, 'domains,', 'N-TAD', and, 'C-TAD'])]). relacion([sujeto(['Both', 'N-TAD', and, 'C-TAD']), verbo([retain]), complemento([redundant, as, well, as, specific, activities, for, proper, hematopoiesis, in, vivo])]). relacion([sujeto(['Globin', gene, switching, is, a, 'complex,', highly]), verbo([regulated]), complemento([process, allowing, expression, of, distinct, globin, genes, at, specific, developmental, stages])]). relacion([sujeto(['Here,', for, the, first, 'time,', we]), verbo([have]), complemento([characterized, all, of, the, zebrafish, globins, based, on, the, completed, genomic, sequence])]). relacion([sujeto(['A']), verbo([conserved]), complemento([regulatory, 'element,', the, locus, control, region, '(', 'LCR),', was, revealed, by, analyzing, 'DNase', 'I', hypersensitive, 'sites,', 'H3K4', trimethylation, marks, and, 'GATA1', binding, sites])]). relacion([sujeto(['Motifs', within, the, zebrafish, 'LCR', include, 'CACCC,', 'GATA,', and, 'NFE2', 'sites,']), verbo([suggesting]), complemento([functional, interactions, with, known, transcription, factors, but, not, the, same, 'LCR', architecture])]). relacion([sujeto(['Our', studies]), verbo([provide]), complemento([a, comprehensive, characterization, of, the, zebrafish, globin, loci, and, clarify, the, regulation, of, globin, switching])]). relacion([sujeto(['The', fetal, and, adult, globin, genes, in, the, human, 'β-globin', cluster, on, chromosome, 11, are, sequentially]), verbo([expressed]), complemento([to, achieve, normal, hemoglobin, switching, during, human, development])]). relacion([sujeto(['For', 'profile-1', 'genes,', where, expression]), verbo([decreased]), complemento([from, day, 7, to, day, 28, ',', we, identified, 2, ',', 102, genes, 'down-regulated', &, 'gt;', 1.5, -, fold])]). relacion([sujeto(['Ingenuity', pathway, analysis, '(', 'IPA)', for, 'profile-1', genes, demonstrated, involvement, of, the, 'Cdc42,', phospholipase, 'C,', 'NF-Kβ,', 'Interleukin-4,', and, p38, mitogen]), verbo([activated]), complemento([protein, kinase, '(', 'MAPK)', signaling, pathways])]). relacion([sujeto(['Transcription', factors, known, to, be]), verbo([involved]), complemento([in, 'γ-and', 'β-globin', regulation, were, identified])]). relacion([sujeto(['The', transcriptome, analysis, completed, with, erythroid, progenitors, grown, in, vitro, identified, groups, of, genes, with, distinct, expression, 'profiles,', which, function, in, metabolic, pathways]), verbo([associated]), complemento([with, cell, 'survival,', 'hematopoiesis,', blood, cells, 'activation,', and, inflammatory, responses])]). relacion([sujeto(['This', study, represents, the, first]), verbo([report]), complemento([of, a, transcriptome, analysis, in, human, primary, erythroid, progenitors, to, identify, transcription, factors, involved, in, hemoglobin, switching])]). relacion([sujeto(['Our', results, also, demonstrate, that, the, in, vitro, liquid, culture, system, is, an, excellent, model, to, define, mechanisms, of, global, gene, expression, and, the, 'DNA-binding', protein, and, signaling, pathways]), verbo([involved]), complemento([in, globin, gene, regulation])]). relacion([sujeto(['Much', remains, unknown, about, the, signals, that]), verbo([induce]), complemento([early, mesoderm, to, initiate, hematopoietic, differentiation])]). relacion([sujeto(['This', coincided, with, severely, reduced, expression, of, embryonic, globin, and, key, bone, morphogenic, protein, '(', 'BMP)']), verbo([target]), complemento(['genes,', including, the, hematopoietic, regulators, 'Scl,', 'Gata1,', 'Gata2,', and, 'Msx-1'])]). relacion([sujeto(['Eng(+)Flk-1(+)', progenitors, coexpressed, 'TGFβ', and, 'BMP', receptors, and]), verbo([target]), complemento([genes])]). relacion([sujeto([5, represents, mesodermal, cells, competent, to]), verbo([respond]), complemento([to, 'TGFβ1,', 'BMP4,', or, 'BMP2,', shaping, their, hematopoietic, 'development,', and, that, 'Eng', acts, as, a, critical, regulator, in, this, process, by, modulating, 'TGF/BMP', signaling])]). relacion([sujeto(['In', children, without, stigmata, the, special, morphology, and, immunophenotype, of, blasts]), verbo([triggered]), complemento([the, screening, for, 'GATA1', mutation, and, trisomy, 21, mosaic])]). relacion([sujeto(['Due', to, clinical, symptoms]), verbo([caused]), complemento([by, the, leukemic, 'blasts,', in, 3, children, 'low-dose', cytarabine, was, applied])]). relacion([sujeto(['GATA1s']), verbo([associated]), complemento([leukemia, has, to, be, excluded, in, all, young, children, with, 'AMKL', '(', &, 'lt;5', years, 'old)', to, prevent, overtreatment])]). relacion([sujeto(['From', our, in, 'situ-based', 'screening,', we]), verbo([have]), complemento([identified, a, novel, 'factor,', 'Vap', '(', 'Vascular', 'Associated', 'Protein)', that, is, predominantly, expressed, in, the, 'ICM,', and, subsequently, enriched, in, endothelial, cells])]). relacion([sujeto(['Vap', expression, in, the, 'ICM', was, drastically]), verbo([suppressed]), complemento([in, the, cloche, mutant, that, has, defects, in, both, vasculogenesis, and, 'hematopoiesis,', whereas, 'Vap', expression, was, not, affected, in, the, vlad, 'tepes/gata1', mutant])]). relacion([sujeto(['Knockdown', of, 'Vap', using, 'anti-sense', morpholinos, '(', 'VAP-MO)', not, only, resulted, in]), verbo([decreased]), complemento([numbers, of, erythrocytes, but, also, in, the, strong, suppression, of, hemoglobin, production])]). relacion([sujeto(['Further,', we]), verbo([found]), complemento([that, 'Vap', knockdown, caused, the, disorganization, of, the, intersegmental, vessels, '(', 'ISVs),', which, show, irregular, branching])]). relacion([sujeto(['In', a, subset, of, 'cells,', both, proteins, are, 'co-expressed', and, immunoreactivities, appear, mutually, excluded, within]), verbo([nuclear]), complemento([spaces])]). relacion([sujeto([',', the, 'aorta-gonad-mesonephros', '(', 'AGM)', and, the, fetal, liver, at, 10.5, -, 11.5, 'dpc,', and]), verbo([found]), complemento([that, only, a, rare, number, of, cells, displayed, this, character])]). relacion([sujeto(['Based', on, this, 'spatial-temporal', 'argument,', we, propose, that, the, earliest, blood, progenitors, emerge, either, directly, from, the, epiblast, or, through, segregation, within, the, allantoic, core, domain, '(', 'ACD)', through, reduction, of, cell, adhesion, and, 'pSmad1/5']), verbo([nuclear]), complemento(['signaling,', followed, by, a, stochastic, decision, toward, a, blood, or, endothelial, fate, that, involves, 'GATA1', and, 'HoxB4,', respectively])]). relacion([sujeto(['A', third, form, in, which]), verbo([binding]), complemento([distributions, are, balanced, may, represent, a, common, condition, shared, by, hemangioblasts, and, 'HSCs'])]). relacion([sujeto(['Children', with, 'Down', syndrome, '(', 'DS)']), verbo([have]), complemento([an, increased, risk, of, 'Acute', 'Myeloid', 'Leukaemia', '(', 'ML-DS),', particularly, megakaryoblastic, 'leukaemia,', which, is, clonally, -, related, to, the, neonatal, myeloproliferative, 'syndrome,', 'Transient', 'Abnormal', 'Myelopoiesis', '(', 'TAM)', unique, to, infants, with, 'DS'])]). relacion([sujeto(['We']), verbo([have]), complemento([briefly, discussed, the, role, of, 'population-based', screening, for, 'TAM', and, development, of, treatment, strategies, to, eliminate, the, preleukaemic, 'TAM', 'clone,', thereby, preventing, 'ML-DS'])]). relacion([sujeto(['The', discovery, of, the, 'JAK2V617F', mutation, in, most, patients, with, 'Ph-negative', myeloproliferative, neoplasms]), verbo([has]), complemento([led, to, the, development, of, 'JAK2', kinase, inhibitors])]). relacion([sujeto(['However,', 'JAK2', inhibitor, therapy]), verbo([has]), complemento([shown, limited, efficacy, and, 'dose-limiting', hematopoietic, toxicities, in, clinical, trials])]). relacion([sujeto(['In', the, present, 'study,', we, describe, the, effects, of, 'vorinostat,', a, 'small-molecule', inhibitor, of, histone, 'deacetylase,', against, cells]), verbo([expressing]), complemento(['JAK2V617F', and, in, an, animal, model, of, polycythemia, vera, '(', 'PV)'])]). relacion([sujeto(['We']), verbo([found]), complemento([that, vorinostat, markedly, inhibited, proliferation, and, induced, apoptosis, in, cells, expressing, 'JAK2V617F'])]). relacion([sujeto(['In', 'addition,', vorinostat, significantly]), verbo([inhibited]), complemento(['JAK2V617F-expressing', mouse, and, human, 'PV', hematopoietic, progenitors])]). relacion([sujeto(['Vorinostat', treatment, also]), verbo([decreased]), complemento([the, mutant, allele, burden, in, mice])]). relacion([sujeto(['Our', results]), verbo([suggest]), complemento([that, vorinostat, may, have, therapeutic, potential, for, the, treatment, of, 'PV', and, other, 'JAK2V617F-associated', myeloproliferative, neoplasms])]). relacion([sujeto(['However,', the, mechanisms]), verbo([regulating]), complemento([human, 'ABO', gene, expression, remain, obscure])]). relacion([sujeto(['This', element, was, shown, to]), verbo([enhance]), complemento(['ABO', promoter, activity, in, an, erythroid, 'cell-specific', manner])]). relacion([sujeto(['Electrophoretic', 'mobility-shift', assays, demonstrated, that, it]), verbo([bound]), complemento([to, the, 'tissue-restricted', transcription, factor, 'GATA-1'])]). relacion([sujeto(['Mutation', of, the, 'GATA', motifs, to, abrogate]), verbo([binding]), complemento([of, this, factor, reduced, the, regulatory, activity, of, the, element])]). relacion([sujeto(['Therefore,', 'GATA-1', appears, to, be]), verbo([involved]), complemento([in, the, 'cell-specific', activity, of, the, element])]). relacion([sujeto(['Furthermore,', we]), verbo([found]), complemento([that, a, partial, deletion, in, intron, 1, involving, the, element, was, associated, with, 'B(m)', phenotypes])]). relacion([sujeto(['Therefore,', it, is, plausible, that, deletion, of, the, erythroid, 'cell-specific', regulatory, element, could, 'down-regulate', transcription, in, the, 'B(m)', 'allele,']), verbo([leading]), complemento([to, reduction, of, 'B-antigen', expression, in, cells, of, erythroid, 'lineage,', but, not, in, 'mucus-secreting', cells])]). relacion([sujeto(['These', results, support, the, contention, that, the, 'enhancer-like', element, in, intron, 1, of, 'ABO']), verbo([has]), complemento([a, significant, function, in, erythroid, cells])]). relacion([sujeto(['Genes']), verbo([involved]), complemento([in, 'host-pathogen', interactions, are, often, strongly, affected, by, positive, natural, selection])]). relacion([sujeto(['The', 'Duffy', antigen, also]), verbo([acts]), complemento([as, a, receptor, for, chemokines, and, is, expressed, in, red, blood, cells, and, many, other, tissues, of, the, body])]). relacion([sujeto(['Because', of, this, dual, 'role,', we, sequenced, a, '~3,000-bp', region, encompassing, the, entire, 'DARC', gene, as, well, as, part, of, its, 5, '\'', and, 3, '\'', flanking, regions, in, a, phylogenetic, sample, of, primates, and, used, statistical, methods, to, evaluate, the, nature, of, selection, pressures]), verbo([acting]), complemento([on, the, gene, during, its, evolution])]). relacion([sujeto(['However,', the, maximum, likelihood, test, in, which, the, gene, was, subdivided, into, different, structural, regions, showed, that, the, known]), verbo([binding]), complemento([region, for, 'P'])]). relacion([sujeto(['In', 'fact,', most, of, the, gene, appears, to, be, under, strong, purifying, 'selection,', but, this, is, not, evident, in, the]), verbo([binding]), complemento([region])]). relacion([sujeto(['We']), verbo([suggest]), complemento([that, the, binding, region, is, under, the, influence, of, two, opposing, selective, 'pressures,', positive, selection, possibly, exerted, by, the, parasite, and, purifying, selection, exerted, by, chemokines])]). relacion([sujeto(['Mast', cell, degranulation, is, a, 'dynamic,', highly, organized, process]), verbo([involving]), complemento([numerous, signaling, molecules, and, enzymes])]). relacion([sujeto(['Although', the, molecular, mechanisms, underlying, 'antigen-mediated', mast, cell, degranulation]), verbo([have]), complemento([been, studied, 'intensively,', little, is, known, about, the, transcriptional, control, of, this, process])]). relacion([sujeto(['Here,', we, show, that, the, hematopoietic, transcription, factors, 'GATA1', and, 'GATA2', are]), verbo([involved]), complemento([in, mast, cell, degranulation, through, the, control, of, phospholipase, 'C-γ1', '(', 'PLC-γ1)', expression])]). relacion([sujeto(['RT-PCR', analyses, showed, that, 'PLC-γ1', expression, was, significantly]), verbo([decreased]), complemento([by, this, 'GATA', factor, repression])]). relacion([sujeto(['Other', 'GATA', factor, 'targets,', such, as, the, previously]), verbo([reported]), complemento([α, and, β, subunits, of, the, 'high-affinity', 'IgE', receptor, '(', 'FcεRI),', were, unaffected])]). relacion([sujeto(['Chromatin', immunoprecipitation, and, luciferase, reporter, assays, demonstrated, that, 'GATA', factors, directly]), verbo([activate]), complemento(['PLC-γ1', gene, transcription, through, a, conserved, 'GATA-binding', motif, that, resides, in, the, 5, '\'', -, upstream, sequence])]). relacion([sujeto(['Furthermore,', we, show, evidence, that, the, 'PLC-γ1', expression, is]), verbo([regulated]), complemento([by, 'GATA2', in, mast, cells, derived, from, mouse, bone, marrow])]). relacion([sujeto(['These', data, indicate, that, 'PLC-γ1', is, a]), verbo([target]), complemento([gene, of, 'GATA', factors, in, mast, cells, and, provide, evidence, that, 'GATA1', and, 'GATA2', control, 'antigen-mediated', mast, cell, degranulation, by, regulating, the, expression, of, 'PLC-γ1'])]). relacion([sujeto(['Individuals', with, 'Down', syndrome, '(', 'DS;', also, known, as, trisomy, 21, ')']), verbo([have]), complemento([a, markedly, increased, risk, of, leukemia, in, childhood, but, a, decreased, risk, of, solid, tumors, in, adulthood])]). relacion([sujeto(['Individuals', who, do, not]), verbo([have]), complemento(['DS', but, bear, germline, 'GATA1', mutations, analogous, to, those, detected, in, individuals, with, 'TMD', and, 'DS-AMKL', are, not, predisposed, to, leukemia])]). relacion([sujeto(['To', better, understand, the, functional, contribution, of, trisomy, 21, to, 'leukemogenesis,', we, used, mouse, and, human, cell, models, of, 'DS', to, reproduce, the, multistep, pathogenesis, of, 'DS-AMKL', and, to, identify, chromosome, 21, genes, that]), verbo([promote]), complemento([megakaryoblastic, leukemia, in, children, with, 'DS'])]). relacion([sujeto(['Furthermore,', through, a, functional, screening, of, the, trisomic, 'genes,', we, demonstrated, that, 'DYRK1A,', which, encodes, 'dual-specificity', 'tyrosine-(Y)-phosphorylation-regulated', kinase, 1, 'A,', was, a, potent, megakaryoblastic, 'tumor-promoting', gene, that, contributed, to, leukemogenesis, through, dysregulation, of]), verbo([nuclear]), complemento([factor, of, activated, 'T', cells, '(', 'NFAT)', activation])]). relacion([sujeto(['Given', that, 'calcineurin/NFAT', pathway, inhibition]), verbo([has]), complemento([been, implicated, in, the, decreased, tumor, incidence, in, adults, with, 'DS,', our, results, show, that, the, same, pathway, can, be, both, proleukemic, in, children, and, antitumorigenic, in, adults])]). relacion([sujeto(['We']), verbo([have]), complemento([reported, the, characterization, of, the, wide, type, of, human, 'IRF-3', 'promoter,', but, the, characterization, of, the, spliced, variant, of, human, 'IRF-3', 'Int2V1', promoter, has, not, been, systematically, analyzed])]). relacion([sujeto(['To', observe, the, spliced, variant, of, human, 'IRF-3', 'promoter,', we]), verbo([have]), complemento([cloned, the, human, 'IRF-3', gene, promoter, region, containing, 300, nucleotides, upstream, the, transcription, start, site, '(', 'TSS)'])]). relacion([sujeto(['This', region, contains, 'GATA1', and, specific, 'protein-1', '(', 'Sp1)', transcription, factor]), verbo([binding]), complemento([sites])]). relacion([sujeto(['However,', overexpression, of, 'Sp1']), verbo([increased]), complemento([the, transcription, activity, by, 2.4, -, fold])]). relacion([sujeto(['Chromosome', 21, gene, dosage, effects, and, truncating, mutations, of, the, 'X-chromosomal', transcription, factor, 'GATA1', synergize, to]), verbo([trigger]), complemento(['TMD', and, 'AMKL', in, most, patients])]). relacion([sujeto(['Here,', we]), verbo([report]), complemento([the, occurrence, of, 'TMD,', which, spontaneously, remitted, and, later, progressed, to, 'AMKL', in, a, patient, without, 'DS', but, with, a, distinct, dysmorphic, syndrome])]). relacion([sujeto(['Genomic', context, analysis, of, proteins, encoded, by, genes, that, are, included, in, the, 'microdeletion,', chromosome, 21, -, encoded, proteins, and, 'GATA1']), verbo([suggests]), complemento([that, the, microdeletion, may, trigger, leukaemogenesis, by, disturbing, the, balance, of, a, hypothetical, regulatory, network, of, normal, megakaryopoiesis, involving, 'PML,', 'SUMO3', and, 'GATA1'])]). relacion([sujeto(['Trib1']), verbo([has]), complemento([been, identified, as, a, myeloid, oncogene, in, a, murine, leukemia, model])]). relacion([sujeto(['This', 'R107L', mutation, remained, in, leukocytes, of, the, remission, stage, in, which, 'GATA1', mutation, 'disappeared,']), verbo([suggesting]), complemento([the, 'TRIB1', mutation, is, an, earlier, genetic, event, in, leukemogenesis])]). relacion([sujeto(['The', bone, marrow, transfer, experiment, showed, that, acute, myeloid, leukemia, development, was, accelerated, by, transducing, murine, bone, marrow, cells, with, the, 'R107L', mutant, in, which, enhancement, of, 'ERK', phosphorylation, and, 'C/EBPα', degradation, by, 'Trib1', expression, was, even, greater, than, in, those]), verbo([expressing]), complemento(['wild-type'])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, 'TRIB1', may, be, a, novel, important, oncogene, for, 'Down', 'syndrome-related', acute, megakaryocytic, leukemia])]). relacion([sujeto(['Substitution', mutations, in, 'GATA1-Nf,', such, as, 'GATA1(V205M)', that, diminish, the, 'GATA1-FOG1', 'association,']), verbo([have]), complemento([been, identified, in, human, thrombocytopenia, and, anemia, cases])]). relacion([sujeto(['A', mouse, model, of, human, thrombocytopenia]), verbo([has]), complemento([been, established, using, a, transgenic, complementation, rescue, 'approach;', 'GATA1-deficient', mice, were, successfully, rescued, from, embryonic, lethality, by, excess, expression, of, 'GATA1(V205G),', but, rescued, adult, mice, suffered, from, severe, thrombocytopenia])]). relacion([sujeto(['Lack', of, these, membrane, proteins]), verbo([provoked]), complemento([perturbation, of, membrane, skeleton])]). relacion([sujeto(['Importantly,', the, red, cells, exhibited]), verbo([increased]), complemento([reactive, oxygen, species, accumulation])]). relacion([sujeto(['These', results, thus, demonstrate, that, the]), verbo([loss]), complemento([of, the, 'GATA1-FOG1', interaction, causes, a, unique, combination, of, membrane, protein, deficiency, and, disturbs, the, function, of, 'GATA1', in, maintaining, erythroid, homeostasis])]). relacion([sujeto(['ZNF143', is, a, 'sequence-specific', 'DNA-binding', protein, that]), verbo([stimulates]), complemento([transcription, of, both, small, 'RNA', genes, by, 'RNA', polymerase, 'II', or, 'III,', or, 'protein-coding', genes, by, 'RNA', polymerase, 'II,', using, separable, activating, domains])]). relacion([sujeto(['We', describe, phenotypic, effects, following, knockdown, of, this, protein, in, developing, 'Danio', rerio, '(', 'zebrafish)', embryos, by, injection, of, morpholino, antisense, oligonucleotides, that]), verbo([target]), complemento([znf143, mRNA])]). relacion([sujeto(['The']), verbo([loss]), complemento([of, function, phenotype, is, pleiotropic, and, includes, a, broad, array, of, abnormalities, including, defects, in, 'heart,', 'blood,', ear, and, midbrain, hindbrain, boundary])]). relacion([sujeto(['The', zebrafish, pax2a, gene, proximal, promoter, contains, two]), verbo([binding]), complemento([sites, for, 'ZNF143,', and, reporter, gene, transcription, driven, by, this, promoter, in, transfected, cells, is, activated, by, this, protein])]). relacion([sujeto(['Normal', development, of, zebrafish, embryos]), verbo([requires]), complemento(['ZNF143'])]). relacion([sujeto(['Furthermore,', the, pax2a, gene, is, probably, one, example, of, many, 'protein-coding', gene]), verbo([targets]), complemento([of, 'ZNF143', during, zebrafish, development])]). relacion([sujeto(['The', transcription, factor, p45]), verbo([nuclear]), complemento(['factor-erythroid-derived', 2, '(', 'NF-E2)', plays, major, roles, in, erythroid, and, megakaryocytic, lineages])]). relacion([sujeto(['Absence', of, p45, 'NF-E2', in, mice]), verbo([leads]), complemento([to, a, twofold, increase, in, serum, erythropoietin, levels])]). relacion([sujeto(['In', the, bone, marrow, of, these, 'animals,', we]), verbo([found]), complemento([a, different, distribution, of, precursor, populations, compared, to, 'wild-type', 'mice,', suggesting, abnormal, differentiation])]). relacion([sujeto(['Loss', of, p45, 'NF-E2', was, also]), verbo([associated]), complemento([with, an, increase, in, splenic, 'erythropoiesis,', as, evidenced, by, an, accumulation, of, early, 'precursors,', 'namely,', late, basophilic, and, polychromatic, erythroblasts])]). relacion([sujeto(['Analysis', of, bone, marrow, samples, revealed]), verbo([increased]), complemento(['GATA1', 'levels,', as, well, as, an, increased, proportion, of, erythroid, cells, arrested, at, the, 'G(1)', stage, of, cell, cycle, in, p45, 'NF-E2-deficient', mice])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, p45, 'NF-E2', is, required, for, the, differentiation, of, erythroid, precursors])]). relacion([sujeto(['Gene', expression, profiling, of, airway, epithelial, and, inflammatory, cells, can, be, used, to, identify, genes]), verbo([involved]), complemento([in, environmental, asthma])]). relacion([sujeto(['LPS', stimulation, resulted, in, pronounced, transcriptional, response, across, all, subjects, in, both, airway, epithelia, and, 'BAL', 'cells,', with, strong, association, to]), verbo([nuclear]), complemento(['factor-κB', and, 'IFN-inducible', genes, as, well, as, signatures, of, other, transcription, factors, '(', 'NRF2,', 'C/EBP,', and, 'E2F1)', and, histone, proteins])]). relacion([sujeto(['DNA', methylation, may]), verbo([regulate]), complemento([gene, expression, by, restricting, the, access, of, transcription, factors])]). relacion([sujeto(['We']), verbo([have]), complemento([previously, demonstrated, that, 'GATA-1', regulates, the, transcription, of, the, 'CCR3', gene, by, dynamically, interacting, with, both, positively, and, negatively, acting, 'GATA', elements, of, high, affinity, binding, in, the, proximal, promoter, region, including, exon, 1])]). relacion([sujeto(['Exon', 1]), verbo([has]), complemento([three, 'CpG', 'sites,', two, of, which, are, positioned, at, the, negatively, acting, 'GATA', elements])]). relacion([sujeto(['We', hypothesized, that, the, methylation, of, these, two, 'CpGs', sites, might, preclude, 'GATA-1']), verbo([binding]), complemento([to, the, negatively, acting, 'GATA', elements, 'and,', as, a, 'result,', increase, the, availability, of, 'GATA-1', to, the, positively, acting, 'GATA', 'element,', thereby, contributing, to, an, increase, in, 'GATA-1-mediated', transcription, of, the, gene])]). relacion([sujeto(['Our', results, demonstrated, that, methylation, of, 'CpG', sites, at, the, negatively]), verbo([acting]), complemento(['GATA', elements, severely, reduced, 'GATA-1', binding, and, augmented, transcription, activity, in, vitro])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, methylation, of, 'CpG', sites, at, the, 'GATA', elements, in, the, regulatory, regions, 'fine-tunes', 'CCR3', transcription])]). relacion([sujeto(['Pre-B-cell', leukemia, homeobox]), verbo([interacting]), complemento([protein, 1, or, human, 'PBX1', interacting, protein, '(', 'PBXIP1/HPIP)', is, a, 'co-repressor', of, 'pre-B-cell', leukemia, homeobox, 1, '(', 'PBX1)', and, is, also, known, to, regulate, estrogen, receptor, functions, by, associating, with, the, microtubule, network])]). relacion([sujeto(['Here,', we, show, that, 'lentivirus-mediated', overexpression, of, 'HPIP', in, human, 'CD34(+)', cells]), verbo([enhances]), complemento([hematopoietic, colony, formation, in, 'vitro,', whereas, 'HPIP', knockdown, leads, to, a, reduction, in, the, number, of, such, colonies])]). relacion([sujeto(['In', 'addition,', forced, expression, of, 'HPIP', in, 'K562', 'cells,', a, multipotent, 'erythro-megakaryoblastic', leukemia, cell, 'line,']), verbo([led]), complemento([to, an, induction, of, erythroid, differentiation])]). relacion([sujeto(['HPIP', overexpression, in, both, 'CD34(+)', and, 'K562', cells, was]), verbo([associated]), complemento([with, increased, activation, of, the, 'PI3K/AKT', 'pathway,', and, corresponding, treatment, with, a, 'PI3K-specific', 'inhibitor,', 'LY-294002,', caused, a, reduction, in, clonogenic, progenitor, number, in, 'HPIP-expressing', 'CD34(+)', cells, and, decreased, 'K562', cell, differentiation])]). relacion([sujeto(['Combined,', these, findings, point, to, an, important, role, of, the, 'PI3K/AKT', pathway, in]), verbo([mediating]), complemento(['HPIP-induced', effects, on, the, growth, and, differentiation, of, hematopoietic, cells])]). relacion([sujeto(['Interestingly,', 'HPIP', gene, expression, was]), verbo([found]), complemento([to, be, induced, in, 'K562', cells, in, response, to, erythroid, differentiation, signals, such, as, 'DMSO', and, erythropoietin])]). relacion([sujeto(['The', erythroid, 'lineage-specific', transcription, factor, 'GATA1']), verbo([binds]), complemento([to, the, 'HPIP', promoter, and, activates, 'HPIP', gene, transcription, in, a, 'CCCTC-binding', factor, '(', 'CTCF)-dependent', manner])]). relacion([sujeto(['Together,', this, study]), verbo([provides]), complemento([evidence, that, 'HPIP', is, a, target, of, 'GATA1', and, 'CTCF', in, erythroid, cells, and, plays, an, important, role, in, erythroid, differentiation, by, modulating, the, 'PI3K/AKT', pathway])]). relacion([sujeto(['Gene', therapy, of, genetic, diseases]), verbo([requires]), complemento([persistent, and, 'position-independent', expression, of, a, therapeutic, transgene])]). relacion([sujeto(['Transcriptional', enhancers]), verbo([binding]), complemento(['chromatin-remodeling', and, modifying, complexes, may, play, a, role, in, shielding, transgenes, from, repressive, chromatin, effects])]). relacion([sujeto(['The', 'GATA1-HS2-modified', vector, allowed, correction, of, murine, 'β-thalassemia', at, low, copy, number, without]), verbo([inducing]), complemento([clonal, selection, of, erythroblastic, progenitors])]). relacion([sujeto(['Chromatin', immunoprecipitation, studies, showed, that, 'GATA1', and, the, 'CBP', acetyltransferase]), verbo([bind]), complemento([to, 'GATA1-HS2,', significantly, increasing, 'CBP-specific', histone, acetylations, at, the, 'LTRs', and, 'β-globin', promoter])]). relacion([sujeto(['Recruitment', of, 'CBP', by, the, 'LTRs', thus, establishes, an, open, chromatin, domain, encompassing, the, entire, 'provirus,', and]), verbo([increases]), complemento([the, therapeutic, efficacy, of, 'β-globin', gene, transfer, by, reducing, expression, variegation, and, epigenetic, silencing])]). relacion([sujeto(['The', system, is, set, up, specifically, for, 'non-invasive', tracking, of, both, stationary, and, circulating, cells, in, adult, zebrafish, '(', 'casper)', that]), verbo([have]), complemento([been, engineered, to, be, optically, transparent])]). relacion([sujeto(['We', demonstrate, initial, testing, of, this, novel, instrument, by, imaging, the, transparent, adult, zebrafish, casper, vasculature, and, tracking, circulating, cells, in, 'CD41-GFP/Gata1-DsRed', transgenic, fish, whose, 'thrombocytes/erythrocytes']), verbo([express]), complemento([the, green, and, red, fluorescent, proteins])]). relacion([sujeto(['Erythroid', cell, dysplasia, observed, in, early, myelodysplastic, syndromes, '(', 'MDS)']), verbo([involves]), complemento([impairment, of, differentiation, and, excess, of, apoptosis, with, a, burst, of, caspase, activation])]). relacion([sujeto(['Analysis', of, gene, expression, in, 'MDS', erythroblasts, obtained, by, ex, vivo, cultures, demonstrates, the, 'down-regulation', of, a, set, of, 'GATA-1', transcriptional]), verbo([target]), complemento(['genes,', including, 'GYPA', that, encodes, glycophorin, 'A', '(', 'GPA),', and, the, 'up-regulation', of, members, of, the, 'HSP70', family])]). relacion([sujeto(['GATA-1', protein, expression, is]), verbo([decreased]), complemento([in, 'MDS', 'erythroblasts,', but, restores, in, the, presence, of, a, 'pan-caspase', inhibitor])]). relacion([sujeto(['In', proliferating, cells]), verbo([expressing]), complemento(['Myb,', enhancers, within, the, 'Myb-Hbs1l', intergenic, region, were, shown, to, form, an, active, chromatin, hub, '(', 'ACH)', containing, the, 'Myb', promoter, and, first, intron])]). relacion([sujeto(['This', first, intron, was]), verbo([found]), complemento([to, harbour, the, transition, site, from, transcription, initiation, to, 'elongation,', which, takes, place, around, a, conserved, 'CTCF', site])]). relacion([sujeto(['We', propose, a, model, for, 'Myb', activation, by, distal, enhancers, dynamically]), verbo([bound]), complemento([by, 'KLF1', and, the, 'GATA1/TAL1/LDB1', 'complex,', which, primarily, function, as, a, transcription, elongation, element, through, chromatin, looping])]). relacion([sujeto(['Although', adults, with, 'Down', syndrome, '(', 'DS)', show, a]), verbo([decreased]), complemento([incidence, of, cancer, compared, to, individuals, without, 'DS,', children, with, 'DS', are, at, an, increased, risk, of, leukemia])]). relacion([sujeto(['Given', that, trisomy, 21, is, a, relatively, common, event, in, hematologic, 'malignancies,', greater, knowledge, of, how, the, genes, on, chromosome, 21, contribute, to, 'DS-AMKL', will]), verbo([increase]), complemento([our, understanding, of, a, broader, class, of, patients, with, leukemia])]). relacion([sujeto(['Polo-like', kinase, 2, '(', 'Plk2)', is, a, member, of, the, 'serine/threonine', protein, kinase, family]), verbo([involved]), complemento([in, 'cell-cycle', regulation, and, cellular, response, to, stresses])]). relacion([sujeto(['Moreover,', using, the, electrophoresis, mobility, shift, assay, and, chromatin, immunoprecipitation, 'assay,', we, identified, two, 'GATA-1', responsive, elements, at, positions, -, 1051, and, -, 949, ',', to, which, 'GATA-1']), verbo([binding]), complemento([was, enhanced, by, 'TSA', under, in, vitro, and, in, vivo, conditions])]). relacion([sujeto(['Immunoprecipitation', and, 'Western', blot, showed, that, the, levels, of, acetylated, 'GATA-1', were]), verbo([increased]), complemento([with, 'TSA', in, 'MG-63', 'cells,', consistent, with, their, binding, affinities, to, the, 'GATA-1', responsive, elements])]). relacion([sujeto(['The', transcriptional, events, that]), verbo([induce]), complemento([etsrp, expression, and, angioblast, specification, are, not, well, understood])]). relacion([sujeto(['To', investigate, the, mechanisms, that, initiate, angioblast, cell, transcription, during, 'embryogenesis,', we]), verbo([have]), complemento([performed, promoter, analysis, of, the, etsrp, locus, in, zebrafish])]). relacion([sujeto(['The', deletion, of, all, 3, regulatory, regions]), verbo([led]), complemento([to, a, near, complete, loss, of, endothelial, expression, from, the, etsrp, promoter])]). relacion([sujeto(['One', of, the, 'enhancers,', located, 2.3, kb, upstream, of, etsrp, contains, a, consensus, 'FOX']), verbo([binding]), complemento([site, that, binds, 'Foxc1a', and, 'Foxc1b', in, vitro, by, 'EMSA', and, in, vivo, using, 'ChIP'])]). relacion([sujeto(['Combined', knockdown, of, 'foxc1a/b,', using, 'morpholinos,']), verbo([led]), complemento([to, a, significant, decrease, in, etsrp, expression, at, early, developmental, stages, as, measured, by, quantitative, reverse, 'transcriptase-polymerase', chain, reaction, and, in, situ, hybridization])]). relacion([sujeto(['TAM', usually, resolves, 'spontaneously,', but, several, studies]), verbo([have]), complemento([associated, this, condition, with, early, 'death,', focusing, on, the, development, of, effective, treatments])]). relacion([sujeto(['We']), verbo([report]), complemento([the, case, of, a, neonate, with, 'DS', who, had, 'TAM', and, novel, 'GATA1', mutation])]). relacion([sujeto(['We']), verbo([have]), complemento([analysed, these, subgroups, of, patients, '(', 11, children, with, 'DS-AMKL,', 12, children, and, four, adults, with, 'non-DS-AMKL)', for, the, presence, of, molecular, 'lesions,', including, mutations, and, chromosomal, abnormalities, studied, by, sequencing, and, single, nucleotide, polymorphism, 'array-based', 'karyotyping,', respectively])]). relacion([sujeto(['In', 'children,', 'AMKL', was]), verbo([associated]), complemento([with, trisomy, 21, '(', somatic, in, 'non-DS-AMKL),', while, numerical, aberrations, of, chromosome, 21, were, only, rarely, associated, with, adult, 'AMKL'])]). relacion([sujeto(['DS-AMKL', was, also]), verbo([associated]), complemento([with, recurrent, somatic, gains, of, 1, q, '(', 4, /, 11, 'DS-AMKL', 'patients)'])]). relacion([sujeto(['In', contrast, to, trisomy, 21, and]), verbo([gains]), complemento([of, 1, 'q,', other, additional, chromosomal, lesions, were, evenly, distributed, between, children, and, adults, with, 'AMKL'])]). relacion([sujeto(['A', mutational, screen]), verbo([found]), complemento(['GATA1', mutations, in, 11, /, 12, 'DS-AMKL,', but, mutations, were, rare, in, paediatric, 'non-DS-AMKL', '(', 1, /, 12, ')', and, adult, 'AMKL', '(', 0, /, 4, ')'])]). relacion([sujeto(['JAK3', '(', 1, /, 11, ')', ',', 'JAK2', '(', 1, /, 11, ')', ',', and, 'TP53', mutations, '(', 1, /, 11, ')', were]), verbo([found]), complemento([only, in, patients, with, 'DS-AMKL'])]). relacion([sujeto(['ASXL1,', 'IDH1/2,', 'DNMT3A,', 'RUNX1', and, 'CBL', mutations, were, not]), verbo([found]), complemento([in, any, of, the, patient, group, 'studied,', while, 'NRAS', mutation, was, identified, in, two, patients, with, paediatric, 'non-DS-AMKL'])]). relacion([sujeto(['Several', infectious, agents]), verbo([have]), complemento([been, related, with, 'SAT'])]). relacion([sujeto(['We', propose, 'that,', the, events, occurring, in, the, patient, may, be, explained, as, result, of, complex, interactions, between, the, individual, genetic, background, and, environmental, exposure, to, infectious, agents, that, generated, a, 'pro-inflammatory', 'status,', where, the, vaccine, was, the]), verbo([trigger]), complemento([for, the, subsequent, alterations, in, thyroid, and, bone, marrow])]). relacion([sujeto(['These', findings, highlight, the, importance, of, immunogenetic, factors]), verbo([involved]), complemento([in, response, to, vaccination, that, is, the, central, theme, in, the, growing, field, of, '\'', 'vaccinomics\''])]). relacion([sujeto(['Acute', megakaryocytic, leukemia, '(', 'AMkL)', in, 'Down', syndrome, '(', 'DS)', children, is, uniformly]), verbo([associated]), complemento([with, somatic, 'GATA1', 'mutations,', which, result, in, the, synthesis, of, a, shorter, protein, '(', 'GATA1s)', with, altered, transactivation, activity, compared, to, the, 'wild-type', 'GATA1'])]). relacion([sujeto(['It', is, not, fully, established, whether, leukemogenesis, and, therapeutic, responses, in, 'DS', 'AMkL', patients, are, due, to]), verbo([loss]), complemento([of, the, 'wild-type', 'GATA1', or, due, to, a, unique, function, of, 'GATA1s'])]). relacion([sujeto(['Stable', clones, of, 'CMK', cells, with]), verbo([decreased]), complemento(['GATA1s', or, 'Bcl-2', levels, were, generated, by, using, 'GATA1-', or, 'BCL-2-specific', lentivirus, shRNAs])]). relacion([sujeto(['In', vivo]), verbo([binding]), complemento([of, 'GATA1s', to, 'IL1A', promoter, was, determined, by, chromatin, immunoprecipitation, assays])]). relacion([sujeto(['Lentivirus', shRNA, knockdown, of, the, 'GATA1', gene, in, the, 'DS', 'AMkL', cell, 'line,', 'CMK', '(', harbors, a, mutated, 'GATA1', gene, and, only]), verbo([expresses]), complemento(['GATA1s),', resulting, in, lower, 'GATA1s', protein, 'levels,', promoted, cell, differentiation, towards, the, megakaryocytic, lineage, and, repressed, cell, proliferation])]). relacion([sujeto(['Our', results]), verbo([suggest]), complemento([that, 'GATA1s', may, facilitate, leukemogenesis, and, potentially, impact, therapeutic, responses, in, 'DS', 'AMkL', by, promoting, proliferation, and, 'survival,', and, by, repressing, megakaryocytic, lineage, 'differentiation,', potentially, by, regulating, expression, of, 'Bcl-2', protein, and, other, relevant, genes])]). relacion([sujeto(['The', 'GATA', family, of, transcription, 'factors,', including, the, founding, 'member,', 'GATA-1,']), verbo([have]), complemento([an, important, role, in, gene, regulation])]). relacion([sujeto(['AMP-activated', protein, kinase, '(', 'AMPK),', a, key, regulator, for, controlling, energy, 'metabolism,', is]), verbo([activated]), complemento([in, response, to, 'ATP-exhausting', stress])]). relacion([sujeto(['We', investigated, whether, cellular, energy, homeostasis, is]), verbo([associated]), complemento([with, maintenance, of, 'self-renewal', and, pluripotency, in, mouse, 'ESCs', '(', 'mESCs)', by, using, 5, -, 'aminoimidazole-4-carboxyamide', ribonucleoside, '(', 'AICAR)', as, an, activator, of, 'AMPK'])]). relacion([sujeto(['We', demonstrate, that, 'AICAR', treatment]), verbo([activates]), complemento([the, 'p53/p21', pathway, and, markedly, inhibits, proliferation, of, 'R1', mESCs, by, inducing, 'G(1)', /, 'S-phase', cell, cycle, 'arrest,', without, influencing, apoptosis])]). relacion([sujeto(['H9', human, 'ESCs', also]), verbo([responded]), complemento([to, 'AICAR', with, induction, of, p53, activation, and, repression, of, 'Nanog', expression])]). relacion([sujeto(['AICAR', reduced, 'Nanog', mRNA, levels, in, mESCs, 'transiently,', an, effect, not, due, to, expression, of, 'miR-134', which, can]), verbo([suppress]), complemento(['Nanog', expression])]). relacion([sujeto(['AICAR']), verbo([induced]), complemento(['Nanog', 'degradation,', an, effect, inhibited, by, 'MG132,', a, proteasome, inhibitor])]). relacion([sujeto(['Although', 'AICAR', reduced, embryoid, body, formation, from, 'mESCs,', it]), verbo([increased]), complemento([expression, levels, of, erythroid, cell, lineage, markers, '(', 'Ter119,', 'GATA1,', 'Klf1,', 'Hbb-b,', and, 'Hbb-bh1)'])]). relacion([sujeto(['Although', erythroid, differentiation, was]), verbo([enhanced]), complemento([by, 'AICAR,', endothelial, lineage, populations, were, remarkably, reduced, in, 'AICAR-treated', cells])]). relacion([sujeto(['Our', results]), verbo([suggest]), complemento([that, energy, metabolism, regulated, by, 'AMPK', activity, may, control, the, balance, of, 'self-renewal', and, differentiation, of, 'ESCs'])]). relacion([sujeto(['Previous', cytogenetic, studies, of, myeloid, and, acute, lymphoblastic, leukemias, in, children, with, 'Down', syndrome, '(', 'ML-DS', and, 'DS-ALL)']), verbo([have]), complemento([revealed, significant, differences, in, abnormality, patterns, between, such, cases, and, acute, leukemias, in, general])]). relacion([sujeto(['In', the, 'ML-DS', 'cases,', a, total, of, 29, imbalances, '(', 20]), verbo([gains]), complemento([and, nine, 'losses)', and, two, partial, uniparental, isodisomies, '(', 'pUPDs)', were, detected])]). relacion([sujeto(['In', 'contrast,', several, frequent, changes, were, identified, in, the, 'DS-ALL', 'cases,', which, harbored, 82, imbalances, '(', 30]), verbo([gains]), complemento([and, 52, 'losses)', and, four, pUPDs])]). relacion([sujeto(['Of', the, 40, large, 'changes,', 28, were]), verbo([gains]), complemento([and, 12, 'losses,', with, +, 'X,', 'dup(Xq),', 'dup(1q),', 'del(7p),', 'dup(8q),', 'del(9p),', 'dup(9p),', 'del(12p),', 'dup(17q),', and, +, 21, being, recurrent])]). relacion([sujeto(['Of', the, 40, microdeletions, 'identified,', several]), verbo([targeted]), complemento([specific, 'genes,', with, the, following, being, repeatedly, 'deleted:', 'BTG1', and, 'CDKN2A/B', '(', 29, '%', of, 'cases),', 'ETV6,', 'IKZF1,', 'PAX5', and, 'SERP2', '(', 18, '%', ')', ',', and, 'BTLA,', 'INPP4B,', 'P2RY8,', and, 'RB1', '(', 12, '%', ')'])]). relacion([sujeto(['Loss', of, the, 'SERP2', and, 'INPP4B', 'genes,', encoding, the, 'stress-associated', endoplasmic, reticulum, protein, family, member, 2, and, the, inositol, polyphosphate, 4, -, 'phosphatase-II,', 'respectively,']), verbo([has]), complemento([previously, never, been, implicated, in, leukemia])]). relacion([sujeto(['Although', deletions, of, the, other, genes]), verbo([have]), complemento([been, associated, with, 'ALL,', the, high, frequency, of, 'BTG1', loss, is, a, novel, finding])]). relacion([sujeto(['In', 'conclusion,', 'ML-DS', and, 'DS-ALL', are, genetically, 'distinct,', with, mainly]), verbo([gains]), complemento([in, 'ML-DS', and, deletions, in, 'DS-ALL'])]). relacion([sujeto(['Furthermore,', 'DS-ALL', is, characterized, by, several, recurrent, gene, 'deletions,', with, 'BTG1']), verbo([loss]), complemento([being, particularly, frequent])]). relacion([sujeto(['Hypoxia-inducible', factor]), verbo([promotes]), complemento([erythropoiesis, through, coordinated, cell, 'type-specific', hypoxia, responses])]). relacion([sujeto(['In', this, 'study,', we, show, that, 'hypoxia-induced', 'GATA1', expression, is]), verbo([mediated]), complemento([by, 'HIF1', in, erythroid, cells])]). relacion([sujeto(['Under', hypoxic, 'conditions,', significantly]), verbo([increased]), complemento(['GATA1', mRNA, and, protein, levels, were, detected, in, 'K562', cells, and, erythroid, induction, cultures, of, 'CD34(+)', haematopoietic, 'stem/progenitor', cells])]). relacion([sujeto(['Enforced', 'HIF1α', expression]), verbo([increased]), complemento(['GATA1', 'expression,', while, 'HIF1α', knockdown, by, 'RNA', interference, decreased, 'GATA1', expression])]). relacion([sujeto(['The', results, from, reporter, gene, and, mutation, analysis]), verbo([suggested]), complemento([that, this, element, is, necessary, for, hypoxic, response])]). relacion([sujeto(['Chromatin', immunoprecipitation, '(', 'ChIP)-PCR', showed, that, the, putative, 'HRE', was]), verbo([recognized]), complemento([and, bound, by, 'HIF1', in, vivo])]). relacion([sujeto(['These', results, demonstrate, that, the, 'up-regulation', of, 'GATA1', during, hypoxia, is, directly]), verbo([mediated]), complemento([by, 'HIF1'])]). relacion([sujeto(['The', mRNA, expression, of, some, erythroid, differentiation, markers, was]), verbo([increased]), complemento([under, hypoxic, 'conditions,', but, decreased, with, 'RNA', interference, of, 'HIF1α', or, 'GATA1'])]). relacion([sujeto(['Flow', cytometry, analysis, also, indicated, that, 'hypoxia,', desferrioxamine, or, 'CoCl(2)']), verbo([induced]), complemento([expression, of, erythroid, surface, markers, 'CD71', and, 'CD235a,', while, expression, repression, of, 'HIF1α', or, 'GATA1', by, 'RNA', interference, led, to, a, decreased, expression, of, 'CD235a'])]). relacion([sujeto(['These', results]), verbo([suggested]), complemento([that, 'HIF1-mediated', 'GATA1', 'up-regulation', promotes, erythropoiesis, in, order, to, satisfy, the, needs, of, an, organism, under, hypoxic, conditions])]). relacion([sujeto(['Here,', we, show, that, regeneration, of, hematopoietic, lineages, following, acute, injury, depends, on, the, activation, of, each, of, these, signaling, pathways, to]), verbo([induce]), complemento([expression, of, key, blood, genes])]). relacion([sujeto(['In', 'addition,', both, 'SMAD1', and, 'TCF7L2', follow, the]), verbo([binding]), complemento([of, the, predominant, lineage, regulator, during, differentiation, from, multipotent, hematopoietic, progenitor, cells, to, erythroid, cells])]). relacion([sujeto(['Furthermore,', induction, of, the, myeloid, lineage, regulator, 'C/EBPα', in, erythroid, cells, shifts]), verbo([binding]), complemento([of, 'SMAD1', to, sites, newly, occupied, by, 'C/EBPα,', whereas, expression, of, the, erythroid, regulator, 'GATA1', directs, 'SMAD1', loss, on, nonerythroid, targets])]). relacion([sujeto(['We', conclude, that, the, regenerative, response]), verbo([mediated]), complemento([by, 'BMP', and, 'Wnt', signaling, pathways, is, coupled, with, the, lineage, master, regulators, to, control, the, gene, programs, defining, cellular, identity])]). relacion([sujeto(['Developmental', and, homeostatic, remodeling, of, cellular, organelles, is]), verbo([mediated]), complemento([by, a, complex, process, termed, autophagy])]). relacion([sujeto(['We', demonstrate, that, the, master, regulator, of, 'hematopoiesis,', 'GATA-1,', directly]), verbo([activates]), complemento([transcription, of, genes, encoding, the, essential, autophagy, component, 'microtubule-associated', protein, 1, light, chain, 3, 'B', '(', 'LC3B)', and, its, homologs, '(', 'MAP1LC3A,', 'GABARAP,', 'GABARAPL1,', and, 'GATE-16)'])]). relacion([sujeto(['In', 'addition,', 'GATA-1', directly]), verbo([activates]), complemento([genes, involved, in, the, 'biogenesis/function', of, 'lysosomes,', which, mediate, autophagic, protein, turnover])]). relacion([sujeto(['We', demonstrate, that, 'GATA-1', utilizes, the, forkhead, protein, 'FoxO3', to]), verbo([activate]), complemento([select, autophagy, genes])]). relacion([sujeto(['GATA-1-dependent', 'LC3B', induction, is, tightly, coupled, to, accumulation, of, the, active, form, of, 'LC3B', and, 'autophagosomes,', which]), verbo([mediate]), complemento([mitochondrial, clearance, as, a, critical, step, in, erythropoiesis])]). relacion([sujeto(['Prx5', is, ubiquitously]), verbo([expressed]), complemento([in, various, tissues, including, mitochondria, and, 'peroxisomes,', implying, that, 'Prx5', functions, as, a, regulator, of, the, cellular, oxidation, state])]). relacion([sujeto(['Prx5', plays, a, critical, role, in, protecting, cells, from, oxidative, stress, by]), verbo([inhibiting]), complemento([the, accumulation, of, reactive, oxygen, species, and, cell, death])]). relacion([sujeto(['Overexpression', of, 'Prx5', in, mammary, tissue, is]), verbo([associated]), complemento([with, poor, prognosis, of, breast, cancer])]). relacion([sujeto(['Analysis', of, the, promoter, region, of, the, 'Prx5', gene, and, reporter, gene, assays, revealed, the, promoter, region, critical, for, 'Prx5', gene, regulation, to, which, the, novel, negative, transcription, 'regulator,', 'GATA1']), verbo([binds]), complemento([in, human, breast, cancer, cell, lines])]). relacion([sujeto(['GATA1', was, further, confirmed, as, a, potential, transcription, factor, for, 'Prx5', gene, expression, in, another, set, of, transfection, assays, using, a, reporter, gene, construct, that, contained, a, mutated, 'GATA1']), verbo([binding]), complemento([site])]). relacion([sujeto(['Direct']), verbo([binding]), complemento([of, 'GATA1', to, the, 'Prx5', promoter, was, demonstrated, using, chromatin, immunoprecipitation, and, electrophoretic, mobility, shift, assays])]). relacion([sujeto(['Finally,', functions, of, 'Prx5']), verbo([associated]), complemento([with, apoptosis, were, examined, in, two, human, breast, cancer, cell, lines, displaying, high, levels, of, either, 'Prx5', or, 'GATA1', expression])]). relacion([sujeto(['Knockdown', of, 'GATA1']), verbo([led]), complemento([to, increased, expression, of, 'Prx5', and, inhibition, of, apoptosis])]). relacion([sujeto(['Our', data]), verbo([suggest]), complemento([that, 'Prx5', may, protect, cells, from, oxidative, 'stress-mediated', apoptosis, in, a, 'GATA1-regulated', manner])]). relacion([sujeto(['The', 'Ldb1/GATA-1/TAL1/LMO2', complex]), verbo([mediates]), complemento(['long-range', interaction, between, the, 'β-globin', locus, control, region, '(', 'LCR)', and, gene, in, adult, mouse, erythroid, 'cells,', but, whether, this, complex, mediates, chromatin, interactions, at, other, developmental, stages, or, in, human, cells, is, unknown])]). relacion([sujeto(['In', addition, to, the, 'LCR,', we]), verbo([found]), complemento([robust, 'NLI', complex, occupancy, at, a, site, downstream, of, the, '(', 'A)γ-globin', gene, within, sequences, of, 'BGL3,', an, intergenic, 'RNA', transcript])]). relacion([sujeto(['In', cells, primarily]), verbo([transcribing]), complemento(['β-globin,', 'BGL3', is, not, transcribed, and, 'BGL3', sequences, are, occupied, by, 'NLI', core, complex, 'members,', together, with, corepressor, 'ETO2', and, by, 'γ-globin', repressor, 'BCL11A'])]). relacion([sujeto(['In', 'contrast,', when, 'γ-globin', transcription, is]), verbo([reactivated]), complemento([in, these, 'cells,', 'ETO2', participation, in, the, 'NLI', complex, at, 'BGL3', is, 'diminished,', as, is, 'BCL11A', 'occupancy,', and, both, 'BGL3', and, 'γ-globin', are, transcribed])]). relacion([sujeto(['We', conclude, that, alternative, 'NLI', complexes]), verbo([mediate]), complemento(['γ-globin', transcription, or, silencing, through, 'long-range', 'LCR', interactions, involving, an, intergenic, site, of, noncoding, 'RNA', transcription, and, that, 'ETO2', is, critical, to, this, process])]). relacion([sujeto(['Understanding', platelet, biology]), verbo([has]), complemento([been, aided, by, studies, of, mice, with, mutations, in, key, megakaryocytic, transcription, factors])]). relacion([sujeto(['We']), verbo([have]), complemento([shown, that, point, mutations, in, the, 'GATA1', cofactor, 'FOG1', that, disrupt, binding, to, the, nucleosome, remodeling, and, deacetylase, '(', 'NuRD)', complex, have, erythroid, and, megakaryocyte, lineages, defects])]). relacion([sujeto(['Mice', that, are, homozygous, for, a, 'FOG1', point, mutation, '(', 'ki/ki),', which, ablates, 'FOG1-NuRD', 'interactions,']), verbo([have]), complemento([platelets, that, display, a, gray, platelet, syndrome, '(', 'GPS)-like', macrothrombocytopenia])]). relacion([sujeto(['These', platelets]), verbo([have]), complemento([few, 'α-granules', and, an, increased, number, of, 'lysosomal-like', vacuoles, on, electron, 'microscopy,', reminiscent, of, the, platelet, in, patients, with, 'GATA1-related', 'X-linked', 'GPS'])]). relacion([sujeto(['We']), verbo([found]), complemento([markedly, deficient, levels, of, 'P-selectin', protein, limited, to, megakaryocytes, and, platelets])]). relacion([sujeto(['Other', 'α-granule', proteins, were]), verbo([expressed]), complemento([at, normal, levels, and, were, appropriately, localized, to, 'α-granule-like', structures])]). relacion([sujeto(['Treatment', of, 'ki/ki', platelets, with, thrombin, failed, to]), verbo([stimulate]), complemento(['Akt', 'phosphorylation,', resulting, in, poor, granule, secretion, and, platelet, aggregation])]). relacion([sujeto(['These', studies, show, that, disruption, of, the, 'GATA1/FOG1/NuRD', transcriptional, system, results, in, a, 'complex,', pleiotropic, platelet, defect, beyond, 'GPS-like', macrothrombocytopenia, and]), verbo([suggest]), complemento([that, this, transcriptional, complex, regulates, not, only, megakaryopoiesis, but, also, 'α-granule', generation, and, signaling, pathways, required, for, granule, secretion])]). relacion([sujeto(['Hmgn2', '(', high, mobility, group, nucleosomal, 2, ')', ',', a, ubiquitous, 'nucleosome-binding', protein, that, unfolds, chromatin, fibres, and]), verbo([enhances]), complemento(['DNA', 'replication,', reportedly, regulates, differentiation, of, epithelial, and, mesenchymal, cells])]). relacion([sujeto(['To', investigate, how, 'Hmgn2']), verbo([regulates]), complemento(['HC', '(', haemopoietic, 'cell)', 'differentiation,', we, quantified, 'Hmgn2', expression, in, 'HCs', of, mouse, 'FL', '(', fetal, 'liver)', during, erythroid, differentiation])]). relacion([sujeto(['Hmgn2', expression, levels, were, &, 'gt;10-fold', higher, in, immature, erythroid, progenitors, than, in, mature, erythroid, 'cells,']), verbo([suggesting]), complemento([that, 'Hmgn2', antagonizes, erythroid, differentiation])]). relacion([sujeto(['There', was, a, 3.3, -, fold]), verbo([decrease]), complemento([in, relatively, mature, 'c-Kit(+)/CD71(+)', erythroid, 'cells,', a, 2.9, -, fold, increase, in, immature, 'c-Kit(+)/CD71(-)', erythroid, cells, in, transfected, 'Friend', 'cells,', a, 1.1, -, fold, decrease, in, relatively, mature, 'CD71(+)/Ter119(+)', erythroid, 'cells,', and, a, 1.7, -, fold, increase, in, relatively, immature, 'c-Kit(+)/CD71(+)', erythroid, cells, in, 'FL', 'HCs', accompanied, by, 'down-regulation', of, genes, encoding, the, erythroid, transcription, 'factors,', 'Gata1', and, 'Klf1'])]). relacion([sujeto(['We']), verbo([have]), complemento([previously, shown, that, perturbed, bone, marrow, progenitor, development, promotes, hyporesponsive, monocytes, following, experimental, burn, sepsis])]). relacion([sujeto(['Clinical', and, experimental, sepsis, is]), verbo([associated]), complemento([with, monocyte, deactivation, and, depletion, of, mDCs])]). relacion([sujeto(['Decrease', in, circulating, 'DCs', is]), verbo([reported]), complemento([in, burn, patients, who, develop, sepsis])]). relacion([sujeto(['In', our, 15, '%', 'TBSA', scald, burn, 'model,', we, demonstrate, a, significant, reduction, in, the, circulating, 'MHC-II(+)', population, and, mDCs, '(', 'Gr1(neg)CD11b(+)CD11c(+))', with, a, corresponding]), verbo([decrease]), complemento([in, bone, marrow, 'MHC-II(+)', cells, and, mDCs, for, up, to, 14, days, following, burn])]). relacion([sujeto(['We', explored, the, underlying, 'mechanism(s)', that]), verbo([regulate]), complemento([bone, marrow, development, of, monocytes, and, 'DCs', following, burn, injury])]). relacion([sujeto(['We']), verbo([found]), complemento([a, robust, bone, marrow, response, with, a, significant, increase, in, multipotential, 'HSCs', '(', 'LSK)', and, bipotential, 'GMPs', following, burn, injury])]). relacion([sujeto(['GMPs', from, burn, mice, exhibit, a, significant, reduction, in, 'GATA-1,', which, is, essential, for, 'DC', 'development,', but]), verbo([express]), complemento([high, levels, of, 'MafB', and, 'M-CSFRs,', both, associated, with, monocyte, production])]). relacion([sujeto(['Monocytes', and, 'DCs']), verbo([expressed]), complemento([50, '%', less, 'MHC-II', in, burn, versus, sham])]). relacion([sujeto(['Transient', silencing, of, 'MafB', '(', 'siRNA)', in, 'GMP-derived', monocytes, from, burn, mice, partially, restored, 'DC', differentiation, deficits, and]), verbo([increased]), complemento(['GATA-1', expression])]). relacion([sujeto(['We']), verbo([provide]), complemento([evidence, that, high, 'MafB', following, burn, plays, an, inhibitory, role, in, 'monocyte-derived', 'DC', differentiation, by, regulating, 'M-CSFR', and, 'GATA-1', expressions])]). relacion([sujeto(['Repetitive', sequences, consist, of, &, 'gt;50%', of, mammalian, genomic, 'DNAs', and, among, these, 'SINEs', '(', short, interspersed]), verbo([nuclear]), complemento(['elements),', e])]). relacion([sujeto(['In', an, effort, to, delineate, the, molecular, 'mechanism(s)']), verbo([involved]), complemento([in, the, blockade, of, the, in, vitro, differentiation, program, of, 'MEL', '(', murine, 'erythroleukaemia)', cells, by, treatment, with, methylation, 'inhibitors,', we, detected, a, 'DNA', region, of, 559, bp, in, chromosome, 7, located, downstream, of, the, 3, '\'', -, end, of, the, 'β(major)', globin, gene, '(', designated, 'B1-559)', with, unique, characteristics])]). relacion([sujeto(['We']), verbo([have]), complemento([fully, characterized, this, 'B1-559', region, that, includes, a, 'B1', 'element,', several, repeats, of, 'ATG', initiation, codons, and, consensus, 'DNA-binding', sites, for, 'erythroid-specific', transcription, factors, 'NF-E2', '(', nuclear, 'factor-erythroid-derived', 2, ')', ',', 'GATA-1', and, 'EKLF', '(', erythroid, 'Krüppel-like', 'factor)'])]). relacion([sujeto(['Fragments', derived, from, 'B1-559', incubated, with]), verbo([nuclear]), complemento([extracts, form, protein, complexes, in, both, undifferentiated, and, differentiated, 'MEL', cells])]). relacion([sujeto(['Notch', signaling]), verbo([has]), complemento([been, linked, to, impaired, erythropoietic, and, megakaryopoietic, development, of, 'CD34+', progenitor, 'cells,', but, its, role, in, 'MDS', is, unclear])]). relacion([sujeto(['We']), verbo([have]), complemento([analyzed, the, transcriptional, activity, of, 'Notch', pathway, elements, and, its, association, with, the, key, erythroid, factor, globin, transcription, factor, 1, '(', 'GATA1)', and, the, apoptosis, regulatory, gene, 'B-cell', 'lymphoma-xl', '(', 'BCLxl)', in, 'MDS'])]). relacion([sujeto(['The', methylation, of, 'GATA1', erythroid, promoter, 'CpG', dinucleotides, flanking, 'cis-regulatory', 'elements,', including, an, 'N-box', suppressor]), verbo([binding]), complemento([site, for, 'HES1', and, a, 'GATA-box', binding, 'site,', was, examined, in, normal, and, 'MDS', erythropoiesis])]). relacion([sujeto(['We']), verbo([have]), complemento([generated, a, kinetic, in, vitro, model, of, 'MDS', erythropoiesis, using, 'CD34+', bone, marrow, cells, from, healthy, donors, '(', n, =, 7, ')', and, patients, with, 'MDS', '(', low, 'risk:', 'RA/n', =, 6, ',', 'RARS/n', =, 3, ;, high, 'risk:', 'RAEB/n', =, 4, ',', 'RAEB-T/n', =, 2, ')'])]). relacion([sujeto(['For', the, 'Notch', pathway, 'elements,', no, conclusive, expression, differences, were]), verbo([found]), complemento([between, 'MDS', and, normal, erythropoiesis])]). relacion([sujeto(['But', we]), verbo([found]), complemento([steadily, 'up-regulated', 'RNA', expression, of, 'GATA1', and, of, 'BCLxl', during, late, normal, erythropoietic, differentiation])]). relacion([sujeto(['In', 'contrast,', during, 'MDS,', erythropoiesis, a]), verbo([loss]), complemento([of, typical, 'up-regulation', of, 'GATA1', and, 'BCLxl', was, observed])]). relacion([sujeto(['Hypermethylation', of, 'CpG', dinucleotides, flanking, the, repressor, 'HES1']), verbo([binding]), complemento([site, within, the, 5, '\'', region, of, 'GATA1', was, detected, particularly, during, late, 'MDS', erythropoiesis])]). relacion([sujeto(['The', higher, residual, 5, '\'', -, 'GATA1', methylation, values, in, 'MDS', erythropoiesis, but, decremental]), verbo([loss]), complemento([thereof, in, normal, erythropoiesis, suggest, a, gene, dose, effect, for, 'GATA1', during, erythropoiesis, being, finely, tuned, by, 'CpG', methylation])]). relacion([sujeto(['Aquaporin', 1, '(', 'Aqp1)', is, a, water, channel, 'protein,']), verbo([expressed]), complemento([widely, in, microvascular, endothelial, cells, and, implicated, in, mammalian, tumor, angiogenesis])]). relacion([sujeto(['However,', its, developmental, expression]), verbo([has]), complemento([not, yet, been, characterized, in, great, detail])]). relacion([sujeto(['An', insertional, 'Et(GBT-B1)tpl1', line, was, identified, that]), verbo([has]), complemento([reporter, insertion, in, the, vicinity, of, the, aqp1a, gene])]). relacion([sujeto(['We', further, show, that, gata1, and, 'etsrp/etv2', function, is]), verbo([required]), complemento([for, hematopoietic, and, endothelial, aqp1a, 'expression,', respectively])]). relacion([sujeto(['β-Lapachone']), verbo([has]), complemento([antitumor, and, wound, 'healing-promoting', activities])]). relacion([sujeto(['To', address, the, potential, influences, of, various, chemicals, on, heart, development, of, zebrafish, 'embryos,', we, previously, treated, zebrafish, embryos, with, chemicals, from, a, 'Sigma', 'LOPAC1280™', library, and]), verbo([found]), complemento([several, chemicals, including, 'β-lapachone', that, affected, heart, morphogenesis])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, the, induction, of, apoptosis, of, endocardium, and, erythrocytes, by, 'β-lapachone', is, mediated, through, an, 'NQO1-', and, 'calcium-dependent', pathway])]). relacion([sujeto(['The', novel]), verbo([finding]), complemento([of, this, study, is, that, 'β-lapachone', affects, heart, morphogenesis, and, function, through, the, induction, of, apoptosis, of, endocardium, and, erythrocytes])]). relacion([sujeto(['Furthermore,', previous, studies, addressing, this, issue]), verbo([have]), complemento([mainly, focused, on, cases, in, which, +, 21, was, part, of, a, complex, karyotype])]). relacion([sujeto(['Partial', uniparental, disomies, '(', 'UPDs)', were]), verbo([found]), complemento([in, five, 'cases;', two, recurrent, 'UPDs', were, 'identified,', namely, 'UPD4q', and, 'UPD7q'])]). relacion([sujeto(['The', 'TET2', mutation, was]), verbo([found]), complemento([in, one, of, the, cases, with, 'UPD4q'])]). relacion([sujeto(['STAT1']), verbo([mediates]), complemento([response, to, interferons, and, regulates, 'immunity,', cell, 'proliferation,', 'apoptosis,', and, sensitivity, of, 'Fanconi', 'Anemia', cells, to, apoptosis, after, interferon, 'signaling;', the, roles, of, 'STAT1', in, 'embryos,', 'however,', are, not, understood])]). relacion([sujeto(['Zebrafish', stat1a, encodes, all, five, domains, of, the, human, 'STAT1-alpha', splice, form, 'but,', like, the, human, 'STAT1-beta', splice, 'variant,', stat1b, lacks, a, complete, transactivation, 'domain;', 'thus,', two, unlinked, zebrafish, paralogs, encode, protein, forms]), verbo([translated]), complemento([from, two, splice, variants, of, a, single, human, 'gene,', as, expected, by, 'sub-functionalization', after, genome, duplication])]). relacion([sujeto(['Phylogenetic', and]), verbo([conserved]), complemento([synteny, studies, showed, that, stat1b, and, stat1a, arose, as, duplicates, in, the, teleost, genome, duplication, '(', 'TGD)', and, clarified, the, evolutionary, origin, of, 'STAT1,', 'STAT2,', 'STAT3,', 'STAT4,', 'STAT5A,', 'STAT5B', and, 'STAT6', by, tandem, and, genome, duplication])]). relacion([sujeto(['Morpholino', knockdown, of, 'stat1b,', but, not, 'stat1a,']), verbo([decreased]), complemento([expression, of, the, myeloid, and, granulocyte, markers, spi, and, mpo, and, increased, expression, of, the, hematopoietic, progenitor, marker, 'scl,', the, erythrocyte, marker, 'gata1,', and, hemoglobin])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, zebrafish, 'Stat1b', promotes, myeloid, development, at, the, expense, of, erythroid, development])]). relacion([sujeto(['A', 'state-dependent', dynamic, network, is, a, collection, of, elements, that]), verbo([interact]), complemento([through, a, 'network,', whose, geometry, evolves, as, the, state, of, the, elements, changes, over, time])]). relacion([sujeto(['We', correlated, these, results, with, the]), verbo([nuclear]), complemento([distribution, of, 'EKLF,', 'RNA-Seq', analysis, of, the, 'transcriptome,', and, the, occupancy, of, other, erythroid, transcription, factors])]). relacion([sujeto(['In', progenitor, 'cells,', 'EKLF', is]), verbo([found]), complemento([predominantly, at, the, periphery, of, the, 'nucleus,', where, 'EKLF', primarily, occupies, the, promoter, regions, of, genes, and, acts, as, a, transcriptional, activator])]). relacion([sujeto(['In', progenitor, 'cells,', 'EKLF']), verbo([modulates]), complemento([general, cell, growth, and, cell, cycle, regulatory, 'pathways,', whereas, in, erythroblasts, 'EKLF', is, associated, with, repression, of, these, pathways])]). relacion([sujeto(['The', 'EKLF', interactome, shows, very, little, overlap, with, the, interactomes, of, 'GATA1,', 'GATA2,', or, 'TAL1,']), verbo([leading]), complemento([to, a, model, in, which, 'EKLF', directs, programs, that, are, independent, of, those, regulated, by, the, 'GATA', factors, or, 'TAL1'])]). relacion([sujeto(['Hematopoietic', stem, cells, '(', 'HSCs)', must, exhibit, tight, regulation, of, both, 'self-renewal', and, differentiation, to]), verbo([maintain]), complemento([homeostasis, of, the, hematopoietic, system, as, well, as, to, avoid, aberrations, in, growth, that, may, result, in, leukemias, or, other, disorders])]). relacion([sujeto([&, 'quot;', 'FSE', cells, had]), verbo([increased]), complemento(['megakaryocyte/platelet', potential, in, culture, and, transplant, settings, and, exhibited, a, higher, clonal, frequency, of, 'colony-forming', 'unit-spleen', activity, compared, with, 'Flk(+)', 'CD150(-)', 'cells,', suggesting, functional, consequences, of, 'GATA1', upregulation, in, promoting, megakaryocyte, and, erythroid, lineage, priming])]). relacion([sujeto(['We']), verbo([provide]), complemento([a, mechanistic, rationale, for, 'megakaryocyte/erythroid', bias, within, 'KLS', 'Flk2(+)', 'cells,', and, demonstrate, how, assessment, of, intracellular, factors, and, signaling, events, can, be, used, to, refine, our, understanding, of, lineage, commitment, during, early, definitive, hematopoiesis])]). relacion([sujeto([miRNA, formation, seems, to, be, dependent, upon, multiple, factors, besides, 'Drosha', and, 'Dicer,', in, a, 'tissue/stage-specific', 'manner,', with, interplay, of, several, specific]), verbo([binding]), complemento([factors])]). relacion([sujeto(['In', the, present, 'study,', we]), verbo([have]), complemento([investigated, transcription, factor, binding, sites, in, and, around, the, genomic, sequences, of, precursor, miRNAs, and, 'RNA-binding', protein, '(', 'RBP)', sites, in, miRNA, precursor, 'sequences,', analysed, and, tested, in, comprehensive, manner])]). relacion([sujeto(['Here,', we]), verbo([report]), complemento([that, miRNA, precursor, regions, are, positionally, enriched, for, binding, of, transcription, factors, as, well, as, 'RBPs', around, the, 3, '\'', end, of, mature, miRNA, region, in, 5, '\'', arm])]). relacion([sujeto(['When', compared, with, 1, kb, 'upstreamregions,', a, sudden, sharp, peak, for]), verbo([binding]), complemento([sites, arises, in, the, enriched, zone, near, the, mature, miRNA, region])]). relacion([sujeto(['Some', specific, groups, of]), verbo([binding]), complemento([factors, and, associated, miRNAs, were, identified])]). relacion([sujeto(['We', also, identified, some, of, the, overrepresented, transcription, factors, and]), verbo([associated]), complemento([miRNAs, with, high, expression, correlation, values, which, could, be, useful, in, 'cancer-related', studies])]). relacion([sujeto(['The', highly, correlated, groups, were]), verbo([found]), complemento([to, host, experimentally, validated, composite, regulatory, 'modules,', in, which, 'Lmo2-GATA1', appeared, as, the, predominant, one])]). relacion([sujeto(['For', many, of, 'RBP-miRNAs', 'associations,', coexpression, similarity, was, also, evident, among, the]), verbo([associated]), complemento([miRNA, common, to, given, 'RBPs,', supporting, the, 'Regulon', 'model,', suggesting, a, common, role, and, common, control, of, these, miRNAs, by, the, associated, 'RBPs'])]). relacion([sujeto(['Most', 'GATA1-regulated', events]), verbo([require]), complemento(['GATA1', to, bind, 'FOG1,', and, essentially, all, 'GATA1-activated', genes, are, cooccupied, by, a, 'TAL1/E2A/LMO2/LDB1', 'complex;', 'however,', it, is, not, known, whether, 'FOG1', and, 'TAL1/E2A/LMO2/LDB1', are, simultaneously, recruited, by, 'GATA1'])]). relacion([sujeto(['Our', structural, data]), verbo([reveal]), complemento([that, the, 'FOG1-binding', domain, of, 'GATA1,', the, 'N', 'finger,', can, also, directly, contact, 'LMO2', and, show, 'that,', despite, the, small, size, '(', &, 'lt; 50', 'residues)', of, the, 'GATA1', 'N', 'finger,', both, 'FOG1', and, 'LMO2', can, simultaneously, bind, this, domain])]). relacion([sujeto(['Taken', 'together,', our, data]), verbo([provide]), complemento([the, first, structural, snapshot, of, multiprotein, complex, formation, at, 'GATA1-dependent', genes, and, support, a, model, in, which, 'FOG1', and, 'TAL1/E2A/LMO2/LDB1', can, cooccupy, 'E-box/WGATAR', sites, to, facilitate, 'GATA1-mediated', activation, of, gene, activation])]). relacion([sujeto(['NUP98-HOXA9', '[', 't(7;11)', '(', 'p15;p15)]', is]), verbo([associated]), complemento([with, inferior, prognosis, in, de, novo, and, 'treatment-related', acute, myeloid, leukaemia, '(', 'AML)', and, contributes, to, blast, crisis, in, chronic, myeloid, leukaemia, '(', 'CML)'])]). relacion([sujeto(['We']), verbo([have]), complemento([engineered, an, inducible, transgenic, zebrafish, harbouring, human, 'NUP98-HOXA9', under, the, zebrafish, 'spi1(pu'])]). relacion([sujeto(['Markers']), verbo([associated]), complemento([with, more, differentiated, myeloid, 'cells,', 'lcp1,', 'lyz,', and, mpx, were, also, 'elevated,', but, to, a, lesser, extent, than, 'spi1,', suggesting, differentiation, of, early, myeloid, progenitors, may, be, impaired, by, 'NUP98-HOXA9'])]). relacion([sujeto(['Following', 'irradiation,', 'NUP98-HOXA9-expressing', embryos, showed]), verbo([increased]), complemento([numbers, of, cells, in, 'G2-M', transition, compared, to, controls, and, absence, of, a, normal, apoptotic, 'response,', which, may, result, from, an, upregulation, of, bcl2])]). relacion([sujeto(['These', data]), verbo([suggest]), complemento(['NUP98-HOXA9-induced', oncogenesis, may, result, from, a, combination, of, defects, in, haematopoiesis, and, an, aberrant, response, to, 'DNA', damage])]). relacion([sujeto(['In', 'summary,', we]), verbo([have]), complemento([identified, an, embryonic, haematopoietic, phenotype, in, a, transgenic, zebrafish, line, that, subsequently, develops, 'MPN'])]). relacion([sujeto(['This', tool]), verbo([provides]), complemento([a, unique, opportunity, for, 'high-throughput', in, vivo, chemical, modifier, screens, to, identify, novel, therapeutic, agents, in, high, risk, 'AML'])]). relacion([sujeto(['Abnormalities', of, pathways]), verbo([involving]), complemento([glycoprotein, '(', 'GP)', mediators, of, adhesion, '(', 'Bernard-Soulier', 'syndrome,', 'platelet-type', von, 'Willebrand', 'disease)', and, aggregation, '(', 'Glanzmann', 'thrombasthenia)', are, the, most, studied, and, affect, the, 'GPIb-IX-V', complex, and, integrin, 'αIIbβ3,', respectively])]). relacion([sujeto(['Defects', of, secretion, from, 'δ-granules', are, accompanied, by, pigment, defects, in, the, 'Hermansky-Pudlak', and, 'Chediak-Higashi', 'syndromes;', they, concern, multiple, genes, and, protein, complexes]), verbo([involved]), complemento([in, secretory, organelle, biogenesis, and, function])]). relacion([sujeto(['Quebec', syndrome, is, linked, to, a, tandem, duplication, of, the, urokinase, plasminogen, activator, '(', 'PLAU)', gene, while, locus, assignment, to, chromosome, 3, p]), verbo([has]), complemento([advanced, the, search, for, the, 'gene(s)', responsible, for, 'α-granule', deficiency, in, the, gray, platelet, syndrome])]). relacion([sujeto(['Defects', of, 'α-granule', biosynthesis, also]), verbo([involve]), complemento([germline, 'VPS33B', mutations, in, the, 'ARC', '(', 'arthrogryposis,', renal, dysfunction, and, 'cholestasis)', syndrome])]). relacion([sujeto(['A', mutation, in, transmembrane, protein, 16, 'F', '(', 'TMEM16F)']), verbo([has]), complemento([been, linked, to, a, defective, procoagulant, activity, and, phosphatidylserine, expression, in, the, 'Scott', syndrome])]). relacion([sujeto(['Interplays', among, 'lineage-specific']), verbo([nuclear]), complemento(['proteins,', chromatin, modifying, 'enzymes,', and, the, basal, transcription, machinery, govern, cellular, 'differentiation,', but, their, dynamics, of, action, and, coordination, with, transcriptional, control, are, not, fully, understood])]). relacion([sujeto(['To', determine, the, predominant, roles, of, chromatin, states, and, factor, occupancy, in, directing, gene, regulation, during, 'differentiation,', we, mapped, chromatin, 'accessibility,', histone, 'modifications,', and]), verbo([nuclear]), complemento([factor, occupancy, 'genome-wide', during, mouse, erythroid, differentiation, dependent, on, the, master, regulatory, transcription, factor, 'GATA1'])]). relacion([sujeto(['Notably,', despite, extensive, changes, in, gene, 'expression,', the, chromatin, state, profiles, '(', proportions, of, a, gene, in, a, chromatin, state, dominated, by]), verbo([activating]), complemento([or, repressive, histone, 'modifications)', and, accessibility, remain, largely, unchanged, during, 'GATA1-induced', erythroid, differentiation])]). relacion([sujeto(['In', 'contrast,', gene, induction, and, repression, are, strongly]), verbo([associated]), complemento([with, changes, in, patterns, of, transcription, factor, occupancy])]). relacion([sujeto(['These', determine, permissiveness, for, 'expression,', with, subsequent, induction, or, repression]), verbo([mediated]), complemento([by, distinctive, combinations, of, transcription, factors])]). relacion([sujeto(['Enhancers', of, transcription]), verbo([activate]), complemento([transcription, via, binding, of, 'sequence-specific', transcription, factors, to, their, target, sites, in, chromatin])]). relacion([sujeto(['In', this, 'report,', we, identify, 'GATA1-bound', distal, sites, 'genome-wide', and]), verbo([find]), complemento([a, global, reorganization, of, the, nucleosomes, at, these, potential, enhancers, during, differentiation, of, hematopoietic, stem, cells, '(', 'HSCs)', to, erythrocytes])]). relacion([sujeto(['Intriguingly,', we]), verbo([find]), complemento([that, the, nucleosome, shifting, specifically, facilitates, binding, of, 'TAL1', but, not, 'GATA1', and, is, linked, to, subsequent, transcriptional, regulation, of, target, genes])]). relacion([sujeto(['Chromatin', immunoprecipitation, followed, by, 'high-throughput', sequencing, '(', 'ChIP-seq)', is, rapidly, replacing, chromatin, immunoprecipitation, combined, with, 'genome-wide', tiling, array, analysis, '(', 'ChIP-chip)', as, the, preferred, approach, for, mapping, 'transcription-factor']), verbo([binding]), complemento([sites, and, chromatin, modifications])]). relacion([sujeto(['This', can]), verbo([lead]), complemento([to, the, omission, of, up, to, 30, '%', of, alignable, reads])]). relacion([sujeto(['Using', human, 'STAT1', and, mouse, 'GATA1', 'ChIP-seq', 'datasets,', we, illustrate, that, incorporation, of, 'multi-reads', significantly]), verbo([increases]), complemento([sequencing, 'depths,', leads, to, detection, of, novel, peaks, that, are, not, otherwise, identifiable, with, 'uni-reads,', and, improves, detection, of, peaks, in, mappable, regions])]). relacion([sujeto(['Overall,', peaks, from, 'multi-read', analysis]), verbo([have]), complemento([similar, characteristics, to, peaks, that, are, identified, by, 'uni-reads', except, that, the, majority, of, them, reside, in, segmental, duplications])]). relacion([sujeto(['We', further, validate, a, number, of, 'GATA1', 'multi-read', only, peaks, by, independent, quantitative, 'real-time', 'ChIP', analysis, and, identify, novel]), verbo([target]), complemento([genes, of, 'GATA1'])]). relacion([sujeto(['These', computational, and, experimental, results, establish, that, 'multi-reads', can, be, of, critical, importance, for, studying, transcription, factor]), verbo([binding]), complemento([in, highly, repetitive, regions, of, genomes, with, 'ChIP-seq', experiments])]). relacion([sujeto(['Overexpression', of, 'pro-inflammatory', 'cytokines,', including, tumour, necrosis, factor, alpha, '(', 'TNFα),']), verbo([has]), complemento([been, implicated, in, the, pathogenesis, of, anaemia, of, inflammation])]). relacion([sujeto(['TNFα']), verbo([suppresses]), complemento([erythroid, colony, formation, via, both, direct, and, indirect, effects, on, haematopoietic, 'progenitors,', often, involving, activation, of, nuclear, factor, '(', 'NF)-κB', signalling, resulting, in, downregulation, of, transcription, factors, critical, for, erythropoiesis])]). relacion([sujeto(['Resveratrol', is, a, flavanol]), verbo([found]), complemento([in, red, wine, grapes, that, possesses, potent, 'anti-inflammatory', 'properties,', but, studies, of, its, impact, on, human, erythropoiesis, have, proven, contradictory])]). relacion([sujeto(['We']), verbo([found]), complemento([that, resveratrol, partially, reverses, the, erythroid, suppressive, effects, of, 'TNFα,', leading, to, significant, recovery, in, burst, forming, 'unit-erythroid', colony, formation, in, human, 'CD34(+)', cells])]). relacion([sujeto(['CD34(+)', cells, 'pre-incubated', with, resveratrol, for, 72, h, in, the, presence, of, 'TNFα']), verbo([inhibited]), complemento(['NF-κB', activation, via, decreased, 'NF-κB', nuclear, localization, without, altering, total, 'NF-κB', protein, levels, and, independent, of, 'IκB', degradation])]). relacion([sujeto(['In', 'conclusion,', resveratrol, may]), verbo([inhibit]), complemento(['TNFα-mediated', 'NF-κB', activation, and, promote, erythropoiesis, in, primary, human, 'CD34(+)', cells])]). relacion([sujeto(['Bromodomain-containing', protein, 1, '(', 'BRD1),', also, known, as, 'BRPF2,']), verbo([has]), complemento([been, considered, a, subunit, of, the, 'MOZ/MORF', 'H3', 'HAT', complex, based, on, analogy, with, 'BRPF1', and, 'BRPF3'])]). relacion([sujeto(['Here', we, show, that, 'BRD1', forms, a, novel, 'HAT', complex, with, 'HBO1', and]), verbo([regulates]), complemento([erythropoiesis])]). relacion([sujeto(['Genome-wide', mapping, in, erythroblasts, demonstrated, that, 'BRD1', and, 'HBO1', largely, colocalize, in, the, genome, and]), verbo([target]), complemento([key, developmental, regulator, genes])]). relacion([sujeto(['Of', 'note,', levels, of, global, acetylation, of, histone, 'H3', at, lysine, 14, '(', 'H3K14)', were, profoundly]), verbo([decreased]), complemento([in, 'Brd1-deficient', erythroblasts, and, depletion, of, 'Hbo1', similarly, affected, 'H3K14', acetylation])]). relacion([sujeto(['Our', findings]), verbo([suggest]), complemento([that, the, 'Hbo1-Brd1', complex, is, the, major, 'H3K14', 'HAT', required, for, transcriptional, activation, of, erythroid, developmental, regulator, genes])]). relacion([sujeto(['In', this, 'study,', we]), verbo([have]), complemento([characterized, the, sequence, 'homology,', gene, 'expression,', hematopoietic, 'functions,', and, regulation, of, sox, genes, in, 'F', group, '(', 'SoxF)', in, zebrafish, embryos])]). relacion([sujeto(['All', 'members,', except, 'sox17,', contained, a, putative, 'β-catenin']), verbo([binding]), complemento([site])]). relacion([sujeto([sox7, and, 18]), verbo([expressed]), complemento([primarily, in, the, vasculature])]). relacion([sujeto([sox17]), verbo([expressed]), complemento([in, the, intermediate, cell, mass, and, its, knockdown, significantly, reduced, primitive, erythropoiesis, at, 18, hours, 'post-fertilization', '(', 'hpf)'])]). relacion([sujeto(['These', defects, could, be]), verbo([prevented]), complemento([by, delaying, its, knockdown, using, a, caged, sox32, morpholino, uncaged, at, 10, hpf])]). relacion([sujeto([sox17, helped, to]), verbo([maintain]), complemento([primitive, 'hematopoiesis,', whereas, sox7, and, sox18, regulated, angiogenesis, and, vasculogenesis])]). relacion([sujeto(['Mammalian', genomes, contain, numerous, regulatory, 'DNA', sites, with, unknown]), verbo([target]), complemento([genes])]). relacion([sujeto(['We', used, mice, with, an, extra, 'β-globin', locus, control, region, '(', 'LCR)', to, investigate, how, a, regulator, searches, the, genome, for]), verbo([target]), complemento([genes])]). relacion([sujeto(['We']), verbo([find]), complemento([that, the, 'LCR', samples, a, restricted, nuclear, 'subvolume,', wherein, it, preferentially, contacts, genes, controlled, by, shared, transcription, factors])]). relacion([sujeto(['This', demonstrates, genetically, that, mammalian, trans, activation, is, 'possible,', but]), verbo([suggests]), complemento([that, it, will, be, rare])]). relacion([sujeto(['Therefore,', 'cell-specific', 'long-range', 'DNA', contacts, can]), verbo([cause]), complemento([variegated, expression])]). relacion([sujeto(['Neonates', with, 'Down', syndrome, '(', 'DS)', are, predisposed, to, developing, transient, abnormal, myelopoiesis, '(', 'TAM)', and, acute, myeloid, leukemia, '(', 'AML)']), verbo([associated]), complemento([with, 'DS'])]). relacion([sujeto(['The', molecular, analysis, of, the, 'GATA1', gene, performed, in, 10, patients, '(', three, 'TAM,', three, 'AML']), verbo([associated]), complemento([with, 'DS', at, 'diagnosis,', one, remission, case, of, 'AML', associated, with, 'DS', and, three, 'DS', without, 'TAM', or, 'AML)'])]). relacion([sujeto(['East', 'Asian', 'DS', neonates, showed, low, frequency, of, 'thrombocytopenia,', uncommon, neutrophilia, and, higher, prevalence, rate, of, 'TAM', compared, to, previous]), verbo([reports]), complemento([from, western, countries])]). relacion([sujeto(['GATA1', mutations, were, identified, in, almost, all, 'TAM', and, 'AML']), verbo([associated]), complemento([with, 'DS', 'samples,', but, were, not, detected, in, the, samples, from, 'DS', without, 'TAM', or, 'AML', associated, with, 'DS'])]). relacion([sujeto(['The', 'c-Jun', 'coactivator,', 'Jun', 'activation-domain']), verbo([binding]), complemento([protein, 1, '(', 'Jab1)', also, known, as, the, fifth, component, of, the, 'COP9', signalosome, complex, '(', 'CSN5),', is, a, novel, candidate, oncogene, whose, aberrant, expression, contributes, to, the, progression, of, breast, carcinoma, and, other, human, cancers])]). relacion([sujeto(['We', identified]), verbo([binding]), complemento([sequences, for, the, 'CCAAT/enhancer', binding, protein, '(', 'C/EBP)', and, 'GATA,', as, well, as, a, signal, transducer, and, activator, of, 'transcription-3', '(', 'Stat3)', consensus, sequence, overlapping, the, 'C/EBP', 'site,', using, 5, '\'', -, deletion, analysis, and, a, gene, reporter, assay])]). relacion([sujeto(['Mutational', analysis, of, these]), verbo([binding]), complemento([sites, was, performed, to, confirm, their, roles, in, promoting, 'Jab1', transcription, in, breast, cancer, cells])]). relacion([sujeto(['We', further, confirmed, these]), verbo([binding]), complemento([sites, using, electrophoretic, mobility, shift, assays, '(', 'EMSAs)', and, chromatin, immunoprecipitation, '(', 'ChIP)', assays])]). relacion([sujeto(['We', also, analyzed, whether, the, 'siRNA-mediated', inactivation, of, 'Stat3', and, 'Src', could, reduce, 'Jab1-promoter', activity, and, whether, 'interleukine-6', '(', 'IL-6)', could]), verbo([mediate]), complemento([increased, 'Jab1', expression, through, 'Stat3', signaling])]). relacion([sujeto(['We', identified]), verbo([binding]), complemento([sequences, for, 'C/EBP,', 'GATA,', as, well, as, a, 'Stat3', consensus, sequence, overlapping, the, 'C/EBP', site, in, the, promoter, region, of, 'Jab1'])]). relacion([sujeto(['C/EBP-beta2', is, a, potential, transcriptional, activator, of, 'Jab1', and, mutation, of, the, 'C/EBP/Stat3']), verbo([binding]), complemento([site, significantly, reduced, 'Jab1-promoter', activity])]). relacion([sujeto(['In', 'addition,']), verbo([inhibiting]), complemento(['Stat3', significantly, reduced, 'Jab1-promoter', activation])]). relacion([sujeto(['EMSA', and, 'ChIP', assays, confirmed, that, 'C/EBP,', 'GATA1', and, 'Stat3']), verbo([bind]), complemento([to, 'Jab1', promoter, in, breast, carcinoma, cells])]). relacion([sujeto(['We', also]), verbo([found]), complemento([that, 'Src,', an, activator, of, 'Stat3,', is, involved, in, 'Jab1-promoter', activation])]). relacion([sujeto([siRNA, knockdown, of, 'Src', reduced, the, 'Jab1-promoter', 'activity,', similar, to, the, results, seen, when, 'Stat3', was]), verbo([inhibited]), complemento([in, breast, carcinoma, cells])]). relacion([sujeto(['Interestingly,', reactivation, of, 'Stat3', in, normal, mammary, epithelial, cells, '(', 'MCF-10A,', 'MCF-10F)', is, sufficient, to]), verbo([reactivate]), complemento(['Jab1', expression])]). relacion([sujeto(['Treatment', with, the, cytokine, 'IL-6', resulted, in]), verbo([increased]), complemento(['Jab1', expression, that, was, blocked, by, inhibition, of, 'Stat3'])]). relacion([sujeto(['These', findings]), verbo([reveal]), complemento([a, novel, mechanism, of, 'Jab1', gene, regulation, and, provide, functional, and, mechanistic, links, between, the, 'Src/Stat3', and, 'IL-6/Stat3', signaling, axes, that, are, involved, in, the, activation, of, 'Jab1', transcription, and, regulation, of, this, novel, oncogenic, protein])]). relacion([sujeto(['Here', we]), verbo([report]), complemento([the, detailed, characterization, of, a, putative, interaction, between, two, transcription, factor, 'proteins,', 'GATA-1', and, 'Krüppel-like', factor, 3, '(', 'KLF3/BKLF)', that, show, robust, interactions, in, 'GST-pulldown', experiments])]). relacion([sujeto(['Attempts', to, map, the, interaction, interface, of, 'GATA-1', on, 'KLF3', using, a, mutagenic, screening, approach, did, not, yield, a, contiguous]), verbo([binding]), complemento([face, on, 'KLF3,', suggesting, that, the, interaction, might, be, 'non-specific'])]). relacion([sujeto(['NMR', experiments, showed, that, the, proteins, do, not]), verbo([interact]), complemento([at, protein, concentrations, of, 50, -, 100, μM])]). relacion([sujeto(['Rather,', the, 'GST', tag, can]), verbo([cause]), complemento([part, of, 'KLF3', to, misfold])]). relacion([sujeto(['In', addition, to, 'misfolding,', the, fact, that, both, proteins, are, 'DNA-binding', domains, appears, to, introduce]), verbo([binding]), complemento([artifacts, '(', possibly, nucleic, acid, 'bridging)', that, cannot, be, resolved, by, the, addition, of, nucleases, or, ethidium, bromide, '(', 'EtBr)'])]). relacion([sujeto(['The', microgravity, environment, of, spaceflight]), verbo([leads]), complemento([to, a, series, of, changes, in, the, human, blood, system])]). relacion([sujeto(['The', aim, of, the, present, study, was, to, examine, the, influence, of, simulated, microgravity, on, the, differentiation, of, 'CD34+', cells, and, to, explore, whether, transcription, factor, 'GATA-1,']), verbo([required]), complemento([for, the, terminal, differentiation, of, committed, erythroid, progenitor, 'cells,', is, involved, in, this, process])]). relacion([sujeto(['CONCLUSIONSs:', 'The', differentiation, of, 'CD3+', 'cells,', and, especially, erythroid, 'differentiation,', was]), verbo([inhibited]), complemento([by, simulated, microgravity, by, a, mechanism, that, appears, to, involve, the, suppression, of, 'GATA-1', mRNA, expression])]). relacion([sujeto(['GATA-1', and, 'NF-E2', are, erythroid, specific, activators, that]), verbo([bind]), complemento([to, the, 'β-globin', locus])]). relacion([sujeto(['GATA-1', or, 'p45/NF-E2', knockdown]), verbo([inhibited]), complemento([the, transcription, of, the, 'γ-globin', 'genes,', hypersensitive, site, '(', 'HS)', formation, in, the, 'LCR', and, chromatin, loop, formation, of, the, 'β-globin', 'locus,', but, histone, acetylation, across, the, locus, was, decreased, only, in, the, case, of, 'GATA-1', knockdown])]). relacion([sujeto(['In', 'p45/NF-E2', knockdown, 'cells,', 'GATA-1']), verbo([binding]), complemento([was, maintained, at, the, 'LCR', 'HSs', and, 'γ-globin', 'promoter,', but, 'NF-E2', binding, at, the, 'LCR', 'HSs', was, reduced, by, 'GATA-1', knockdown, regardless, of, the, amount, of, 'p45/NF-E2', in, 'K562', cells])]). relacion([sujeto(['These', results, indicate, that, histone, acetylation, is, dependent, on, 'GATA-1', 'binding,', but, the]), verbo([binding]), complemento([of, 'GATA-1', is, not, sufficient, for, the, 'γ-globin', 'transcription,', 'HS', formation, and, chromatin, loop, formation, and, 'NF-E2', is, required])]). relacion([sujeto(['This', idea, is, supported, by, the, distinctive]), verbo([binding]), complemento([pattern, of, 'CBP', and, 'Brg1', in, the, 'β-globin', locus])]). relacion([sujeto(['Furthermore', 'GATA-1-dependent', loop, formation, between, 'HS5', and, 3, '\'', 'HS1']), verbo([suggests]), complemento([correlation, between, histone, modifications, and, chromatin, looping])]). relacion([sujeto(['Hematopoiesis']), verbo([involves]), complemento([an, elaborate, regulatory, network, of, transcription, factors, that, coordinates, the, expression, of, multiple, downstream, 'genes,', and, maintains, homeostasis, within, the, hematopoietic, system, through, the, accurate, orchestration, of, cellular, 'proliferation,', differentiation, and, survival])]). relacion([sujeto(['The', 'GATA', family, of]), verbo([nuclear]), complemento([regulatory, proteins, serves, as, a, prototype, for, the, action, of, 'lineage-restricted', transcription, factors])]). relacion([sujeto(['GATA1', and, 'GATA2', are]), verbo([expressed]), complemento([principally, in, hematopoietic, 'lineages,', and, have, essential, roles, in, the, development, of, multiple, hematopoietic, 'cells,', including, erythrocytes, and, megakaryocytes])]). relacion([sujeto(['Hematopoiesis', is, evolutionarily]), verbo([conserved]), complemento([from, zebrafish, to, 'mammals,', and, this, includes, both, primitive, and, definitive, waves, during, embryogenesis])]). relacion([sujeto(['We', show, here, that, the]), verbo([loss]), complemento([of, 6, small, 'ubiquitin-related', modifier, '(', 'SUMO)', paralogs, triggers, a, sharp, 'up-regulation', of, the, 'myeloid-specific', marker, mpo, and, 'down-regulation', of, the, 'erythroid-specific', marker, gata1, in, 'myelo-erythroid', progenitor, cells, '(', 'MPCs)', in, the, intermediate, cell, mass, '(', 'ICM)', during, primitive, hematopoiesis])]). relacion([sujeto(['A', 'SUMO-CCAAT/enhancer-binding', protein, α, '(', 'SUMO-C/ebpα)', fusion, restores, the, normal, 'myelopoiesis/erythropoiesis', 'balance,']), verbo([suggesting]), complemento([that, sumoylation, status, of, 'C/ebpα', contributes, to, 'myelo-erythroid', lineage, determination])]). relacion([sujeto(['Our', results, therefore, implicate, sumoylation, in, early, lineage, determination, and]), verbo([reveal]), complemento([the, possible, molecular, mechanism, underlying, the, puzzling, biased, primitive, hematopoiesis, in, vertebrates])]). relacion([sujeto(['Here,', we]), verbo([report]), complemento([the, 'genome-wide', binding, sites, for, the, five, key, hematopoietic, transcription, 'factors--GATA1,', 'GATA2,', 'RUNX1,', 'FLI1,', and, 'TAL1/SCL--in', primary, human, megakaryocytes])]). relacion([sujeto(['Statistical', analysis, of, the, 17, ',', 263, regions]), verbo([bound]), complemento([by, at, least, one, factor, demonstrated, that, simultaneous, binding, by, all, five, factors, was, the, most, enriched, pattern, and, often, occurred, near, known, hematopoietic, regulators])]). relacion([sujeto(['Eight', genes, not, previously, appreciated, to, function, in, hematopoiesis, that, were]), verbo([bound]), complemento([by, all, five, factors, were, shown, to, be, essential, for, thrombocyte, 'and/or', erythroid, development, in, zebrafish])]). relacion([sujeto(['Recent', data, demonstrate, that, small, synthetic, compounds, specifically]), verbo([targeting]), complemento([bromodomain, proteins, can, modulate, the, expression, of, 'cancer-related', or, inflammatory, genes])]). relacion([sujeto(['Although', these, studies]), verbo([have]), complemento([focused, on, the, ability, of, bromodomains, to, recognize, acetylated, 'histones,', it, is, increasingly, becoming, clear, that, 'histone-like', modifications, exist, on, other, important, 'proteins,', such, as, transcription, factors])]). relacion([sujeto(['However,', our, understanding, of, the, molecular, mechanisms, through, which, these, modifications]), verbo([modulate]), complemento([protein, function, is, far, from, complete])]). relacion([sujeto(['We']), verbo([have]), complemento([recently, identified, the, 'bromodomain-containing', protein, 'Brd3', as, a, cofactor, that, interacts, with, acetylated, 'GATA1', and, shown, that, this, interaction, is, essential, for, the, targeting, of, 'GATA1', to, chromatin])]). relacion([sujeto(['Our', data]), verbo([reveal]), complemento([for, the, first, time, the, molecular, details, of, an, interaction, between, a, transcription, factor, bearing, multiple, acetylation, modifications, and, its, cognate, recognition, module])]). relacion([sujeto(['We', also, show, that, this, interaction, can, be]), verbo([inhibited]), complemento([by, an, acetyllysine, 'mimic,', highlighting, the, importance, of, further, increasing, the, specificity, of, compounds, that, target, bromodomain, and, extraterminal, '(', 'BET)', bromodomains, in, order, to, fully, realize, their, therapeutic, potential])]). relacion([sujeto(['Ribosomal', proteins, '(', 'RPs),', structural, components, of, the, ribosome]), verbo([involved]), complemento([in, protein, 'synthesis,', are, of, significant, importance, in, all, organisms])]). relacion([sujeto(['Previous', studies]), verbo([have]), complemento([suggested, that, some, 'RPs', may, have, other, functions, in, addition, to, assembly, of, the, ribosome])]). relacion([sujeto(['The', small, ribosomal, subunits, 'RPS7,']), verbo([has]), complemento([been, reported, to, modulate, the, 'mdm2-p53', interaction])]). relacion([sujeto(['In', 'RPS7-deficient', 'embryos,', p53, was, 'activated,', and, its, downstream]), verbo([target]), complemento([genes, and, biological, events, were, 'induced,', including, apoptosis, and, cell, cycle, arrest])]). relacion([sujeto(['The', matrix, metalloproteinase, '(', 'mmp)', family, genes, were, also]), verbo([activated]), complemento([in, 'RPS7', 'morphants,', indicating, that, improper, cell, migration, might, also, cause, development, defects])]). relacion([sujeto(['These', results, strengthen, the, hypothesis, that, specific, ribosomal, proteins]), verbo([regulate]), complemento([p53, and, that, their, deficiency, affects, hematopoiesis])]). relacion([sujeto(['These', specific, functions, of, 'RPS7', may]), verbo([provide]), complemento([helpful, clues, to, study, the, roles, of, 'RPs', in, human, disease])]). relacion([sujeto(['Here', we, present, a, unique, genetic, profile, that, includes, 'bi-allelic', deletions, within, 13, 'q14,', where, the, retinoblastoma, tumor, suppressor, gene, '(', 'RB1)', 'resides,', as, well, as, isolated, trisomy, 21, without, a, concomitant, mutation, in, the, hematopoietic, transcription, factor, 'GATA1s', and, translocation, '(', 17, ;, 22, ')', ',', that, does, not]), verbo([involve]), complemento([the, megakaryoblastic, leukemia, 1, '(', 'MKL1)', gene, located, on, chromosome, 22])]). relacion([sujeto(['Acetylation', of, histones]), verbo([triggers]), complemento([association, with, 'bromodomain-containing', proteins, that, regulate, diverse, 'chromatin-related', processes])]). relacion([sujeto(['Although', acetylation, of, transcription, factors]), verbo([has]), complemento([been, appreciated, for, some, 'time,', the, mechanistic, consequences, are, less, well, understood])]). relacion([sujeto(['The', hematopoietic, transcription, factor, 'GATA1', is, acetylated, at]), verbo([conserved]), complemento([lysines, that, are, required, for, its, stable, association, with, chromatin])]). relacion([sujeto(['We', show, that, the, 'BET', family, protein, 'Brd3']), verbo([binds]), complemento([via, its, first, bromodomain, '(', 'BD1)', to, 'GATA1', in, an, 'acetylation-dependent', manner, in, vitro, and, in, vivo])]). relacion([sujeto(['Mutation', of, a, single, residue, in, 'BD1', that, is]), verbo([involved]), complemento([in, 'acetyl-lysine', binding, abrogated, recruitment, of, 'Brd3', by, 'GATA1,', demonstrating, that, acetylation, of, 'GATA1', is, essential, for, 'Brd3', association, with, chromatin])]). relacion([sujeto(['Notably,', 'Brd3', is]), verbo([recruited]), complemento([by, 'GATA1', to, both, active, and, repressed, target, genes, in, a, fashion, seemingly, independent, of, histone, acetylation])]). relacion([sujeto(['Anti-Brd3', 'ChIP', followed, by, massively, parallel, sequencing, in, 'GATA1-deficient', erythroid, precursor, cells, and, those, that, are, 'GATA1', replete, revealed, that, 'GATA1', is, a, major, determinant, of, 'Brd3', recruitment, to, genomic]), verbo([targets]), complemento([within, chromatin])]). relacion([sujeto(['A', pharmacologic, compound, that, occupies, the, 'acetyl-lysine']), verbo([binding]), complemento([pockets, of, 'Brd3', bromodomains, disrupts, the, 'Brd3-GATA1', 'interaction,', diminishes, the, chromatin, occupancy, of, both, 'proteins,', and, inhibits, erythroid, maturation])]). relacion([sujeto(['Together', these, findings]), verbo([provide]), complemento([a, mechanism, for, 'GATA1', acetylation, and, suggest, that, 'Brd3', &, 'quot;reads"', acetyl, marks, on, nuclear, factors, to, promote, their, stable, association, with, chromatin])]). relacion([sujeto(['Protein', 'Inhibitor', of, 'Activated', 'Signal', 'Transducer', and, 'Activators', of, 'Transcription', 3, '(', 'PIAS3)', is, a, molecule, that]), verbo([regulates]), complemento(['STAT3', and, has, antiproliferative, properties])]). relacion([sujeto(['We', identify, novel, transcription, factor]), verbo([binding]), complemento([partners, for, 'PIAS3', including, 'ETS,', 'EGR1,', 'NR1I2,', and, 'GATA1'])]). relacion([sujeto(['PIAS3']), verbo([binds]), complemento([to, these, factors, and, regulates, their, transcriptional, effects, resulting, in, alterations, in, canonical, pathways, including, 'Wnt/β-catenin', signaling, and, functions, such, as, cell, death, and, proliferation])]). relacion([sujeto(['A', model, is, proposed, by, which, 'PIAS3', effects, 'EGR1']), verbo([regulated]), complemento([pathways])]). relacion([sujeto(['Bone', morphogenetic, protein, '(', 'BMP)', signaling]), verbo([regulates]), complemento([embryonic, hematopoiesis, via, 'receptor-mediated', activation, of, downstream, 'SMAD', 'proteins,', including, 'SMAD1'])]). relacion([sujeto(['In', previous, 'work,', we, showed, that, 'Smad1', expression, is, sufficient, to]), verbo([enhance]), complemento([commitment, of, mesoderm, to, hemangioblast, fate])]). relacion([sujeto(['We', also]), verbo([found]), complemento([indirect, evidence, to, support, a, subsequent, repressive, function, for, 'Smad1', in, hematopoiesis])]). relacion([sujeto(['This']), verbo([involves]), complemento([enhanced, expression, levels, for, genes, specific, to, 'hematopoiesis,', including, 'Gata1,', 'Runx1', and, 'Eklf,', rather, than, factors, required, for, earlier, specification, of, the, hemangioblast])]). relacion([sujeto(['The', phenotype, correlates, with]), verbo([increased]), complemento([nuclear, 'SMAD2', 'activity,', indicating, molecular, 'cross-regulation', between, the, 'BMP', and, 'TGF-β', signaling, pathways])]). relacion([sujeto(['Consistent', with, this, 'mechanism,', hematopoiesis, was]), verbo([enhanced]), complemento([when, 'Smad2', was, directly, expressed, during, this, same, developmental, window])]). relacion([sujeto(['Therefore,', this, study]), verbo([reveals]), complemento([a, temporally, defined, function, for, 'Smad1', in, restricting, the, expansion, of, early, hematopoietic, progenitors])]). relacion([sujeto(['Many', physiological, perturbations, can]), verbo([cause]), complemento([anemia])]). relacion([sujeto(['In', cancer, 'patients,', activation, of, the, immune, system]), verbo([leads]), complemento([to, the, production, of, proinflammatory, cytokines, including, tumor, necrosis, factor, alpha, '(', 'TNFα),', that, have, been, shown, to, inhibit, 'red-cell', production, via, poorly, understood, mechanisms])]). relacion([sujeto(['Treatment', of, anemia, by, human, recombinant, erythropoietin, '(', 'EPO)', is, strongly, suspected, to]), verbo([induce]), complemento([tumor, growth])]). relacion([sujeto(['This', study, focuses, on, the, mechanisms]), verbo([involved]), complemento([in, 'TNFα-mediated', inhibition, of, erythropoiesis])]). relacion([sujeto(['Erythropoiesis', was, achieved, in, vitro, by]), verbo([stimulating]), complemento([cells, with, 'EPO'])]). relacion([sujeto(['The', amount, of, 'hemoglobin-producing', cells, as, well, as, the, expression, of, 'GATA-1']), verbo([target]), complemento(['erythro-specific', genes, '(', 'EPO', 'receptor,', glycophorin, 'A', and, 'globins)', was, found, decreased, after, 'TNFα', treatment, of, 'HSPC'])]). relacion([sujeto(['In', 'correlation,', 'TNFα']), verbo([induced]), complemento([the, expression, of, the, transcription, factors, 'GATA-2', and, 'PU'])]). relacion([sujeto(['In', this, 'regard,', 'TNFα']), verbo([promoted]), complemento([the, formation, of, the, 'GATA-1/PU'])]). relacion([sujeto([1, complex, that]), verbo([has]), complemento([been, reported, to, block, the, transcriptional, activity, of, 'GATA-1'])]). relacion([sujeto(['Our', results, clearly, demonstrate, that, 'TNFα']), verbo([prevents]), complemento(['EPO-mediated', erythropoiesis, of, 'HSPC', as, an, early, 'event,', by, directly, affecting, erythroid, cell, development])]). relacion([sujeto(['No', known, recurrent, cytogenetic, abnormality, is]), verbo([associated]), complemento([with, this, leukemia])]). relacion([sujeto(['Rare', cases, of, 't(X;6)(p11;q23)', translocation]), verbo([have]), complemento([been, described, but, these, were, sporadic])]). relacion([sujeto(['We']), verbo([report]), complemento([here, 4, cases, of, 'ABL', with, a, 't(X;6)(p11;q23)', translocation, occurring, in, male, infants])]). relacion([sujeto(['Recent', studies]), verbo([suggest]), complemento([that, the, hematopoietic, and, cardiac, lineages, have, close, ontogenic, 'origins,', and, that, an, early, mesodermal, cell, population, has, the, potential, to, differentiate, into, both, lineages])]). relacion([sujeto(['Studies', also]), verbo([suggest]), complemento([that, specification, of, these, lineages, is, inversely, regulated])]). relacion([sujeto(['Here,', we, show, that, 'Nkx2-5']), verbo([regulates]), complemento([the, 'hematopoietic/erythroid', fate, of, the, mesoderm, precursors, early, during, cardiac, morphogenesis])]). relacion([sujeto(['Using', transgenic, technologies, to, isolate, 'Nkx2-5']), verbo([expressing]), complemento(['cells,', we, observed, an, induction, of, the, erythroid, molecular, 'program,', including, 'Gata1,', in, the, 'Nkx2-5-null', embryos])]). relacion([sujeto(['We', further, observed, that, overexpression, of, 'Nkx2-5', with, an, 'Nkx2-5-inducible', embryonic, stem, cell, system, significantly, repressed, 'Gata1', gene, expression, and]), verbo([suppressed]), complemento([the, 'hematopoietic/erythroid', 'potential,', but, not, the, endothelial, 'potential,', of, the, embryonic, stem, cells])]). relacion([sujeto(['In', 'addition,', we, demonstrated, that, 'Nkx2-5']), verbo([binds]), complemento([to, the, 'Gata1', gene, enhancer, and, represses, the, transcriptional, activity, of, the, 'Gata1', gene])]). relacion([sujeto(['Our', results, demonstrate, that, the, 'hematopoietic/erythroid', cell, fate, is]), verbo([suppressed]), complemento([via, 'Nkx2-5', during, mesodermal, fate, 'determination,', and, that, the, 'Gata1', gene, is, one, of, the, targets, that, are, suppressed, by, 'Nkx2-5'])]). relacion([sujeto(['Specifically', they, are, thought, to]), verbo([regulate]), complemento([the, differentiation, of, progenitor, cells, into, the, 'granulocyte/macrophage', lineage, and, the, 'erythrocyte/megakaryocite', lineage])]). relacion([sujeto(['While', several, mathematical, models]), verbo([have]), complemento([been, proposed, to, investigate, the, interaction, between, the, transcription, factors, in, recent, 'years,', there, is, still, debate, about, the, nature, of, the, progenitor, state, in, the, dynamical, 'system,', and, whether, the, existing, models, adequately, capture, new, knowledge, about, the, interactions, gleaned, from, experimental, data])]). relacion([sujeto(['In', this, paper, we, analyse, the, four, existing, 'models,', and, propose, an, alternative, model, which, is, shown, to, demonstrate, a, rich, variety, of, dynamical, systems, behaviours]), verbo([found]), complemento([across, the, existing, 'models,', including, both, bistability, and, tristability, required, for, modelling, the, undifferentiated, progenitors])]). relacion([sujeto(['Classical', swine, fever, '(', 'CSF)']), verbo([causes]), complemento([severe, disease, in, 'pigs,', characterized, by, 'hemorrhage,', 'fever,', and, leucopenia])]). relacion([sujeto(['A', primary]), verbo([target]), complemento([of, the, virus, is, endothelial, 'cells,', where, a, 'pro-inflammatory', and, 'pro-coagulant', response, occurs, with, downregulation, of, gap, junctional, 'communication;', these, changes, establish, a, basis, for, haemostatic, imbalance])]). relacion([sujeto(['The', aim, of, this, study, was, to]), verbo([gain]), complemento([an, understanding, of, the, effect, of, classical, swine, fever, virus, '(', 'CSFV)', on, endothelial, nitric, oxide, synthase, '(', 'eNOS)', expression, and, nitric, oxide, '(', 'NO)', bioavailability])]). relacion([sujeto(['Without', influence, from, the, progeny, virus, 'titer,', the]), verbo([decrease]), complemento([in, eNOS, protein, was, reversed, by, an, 'ERK', inhibitor, '(', 'PD98059)', and, two, 'PI3/Akt', inhibitors, '(', 'LY294002', and, 'wortmannin)'])]). relacion([sujeto(['In', 'addition,', we]), verbo([found]), complemento([that, the, transcription, factors, 'AP1,', 'Sp1,', and, 'GATA1/2', may, be, involved, in, the, downregulation, of, eNOS, promoter, activity])]). relacion([sujeto(['Use', of, iPSC, lines, for, future, hematotherapy, will]), verbo([require]), complemento([examination, of, their, hematopoietic, potential])]). relacion([sujeto(['Overall,', we]), verbo([find]), complemento([that, mesodermal, and, hematopoietic, potential, varies, among, iPSCs, from, an, identical, tissue, source, and, that, 'c-Myc', expression, likely, underlies, these, differences])]). relacion([sujeto(['Identification', of, hematopoietic, progenitor, cells, in, the, zebrafish, '(', 'Danio', 'rerio)']), verbo([has]), complemento([been, hindered, by, a, lack, of, functional, assays, to, gauge, proliferative, potential, and, differentiation, capacity])]). relacion([sujeto(['From', adult, whole, kidney, 'marrow,', erythropoietin, was]), verbo([required]), complemento([to, support, erythroid, colony, 'formation,', and, granulocyte, 'colony-stimulating', factor, was, required, to, support, the, formation, of, colonies, containing, 'neutrophils,', 'monocytes,', and, macrophages])]). relacion([sujeto(['Together,', these, experiments]), verbo([provide]), complemento([the, first, report, of, clonal, hematopoietic, progenitor, assays, in, the, zebrafish, and, establish, the, 'number,', 'characteristics,', and, kinetics, of, myeloerythroid, progenitors, during, both, 'steady-state', and, stress, hematopoiesis])]). relacion([sujeto(['After', the, treatment, with, these, benzene, metabolites, at, the, concentrations, with, no, obvious, 'cytotoxicity,', the, 'hemin-induced', hemoglobin, synthesis, in, 'K562', cells]), verbo([decreased]), complemento([in, a, 'concentration-', and, 'time-dependent', 'manner,', and, the, expression, of, 'CD71', and, 'GPA', protein, on, the, surface, of, 'K562', cells, was, also, inhibited])]). relacion([sujeto(['The', 'hemin-induced', expression, of, globin, 'genes,', including, 'α-,', 'β-', and, 'γ-globin', 'genes,', and, the, gene, encoding, the, heme, synthesis, enzyme, porphobilinogen, deaminase, was]), verbo([inhibited]), complemento([by, benzene, metabolites])]). relacion([sujeto(['When', the, 'K562', cells, were, pretreated, with, benzene, 'metabolites,', the, 'hemin-induced', expression, of, two, transcription, factor, genes, 'GATA-1', and, 'NF-E2', was, distinctly, 'reduced,', and, the, 'pre-treatment', with, benzene, metabolites]), verbo([promoted]), complemento([the, decrease, of, the, mRNA, level, of, transcription, factor, gene, 'GATA-2', by, hemin])]). relacion([sujeto(['These', results, indicated, that, benzene, metabolites]), verbo([inhibited]), complemento([the, 'hemin-induced', erythroid, differentiation, through, affecting, the, transcription, of, the, erythroid, related, genes])]). relacion([sujeto(['Such', changes, appear, to, be, important, for]), verbo([regulating]), complemento(['transcription,', although, many, questions, remain, regarding, how, loci, reversibly, transit, in, and, out, of, their, territories, and, the, functional, significance, of, subnuclear, transitions])]). relacion([sujeto(['In', a, genetic, complementation, assay, in, 'GATA-1-null', 'cells,', 'GATA-1', expels, 'FOG-1-dependent']), verbo([target]), complemento([genes, from, the, nuclear, periphery, during, erythroid, 'maturation,', but, the, underlying, mechanisms, are, unknown])]). relacion([sujeto(['We', demonstrate, that, 'GATA-1']), verbo([induces]), complemento([extrusion, of, the, 'β-globin', locus, away, from, its, chromosome, territory, at, the, nuclear, 'periphery,', and, extrusion, precedes, the, 'maturation-associated', transcriptional, surge, and, morphological, transition])]). relacion([sujeto(['FOG-1', and, its, interactor, 'Mi-2β,', a, chromatin, remodeling, factor, commonly, linked, to, 'repression,', were]), verbo([required]), complemento([for, locus, extrusion])]). relacion([sujeto(['Erythroid', 'Krüppel-like', 'factor,', a, pivotal, regulator, of, erythropoiesis, that, often, 'co-occupies', chromatin, with, 'GATA-1,', also]), verbo([promoted]), complemento([locus, extrusion])]). relacion([sujeto(['These', results]), verbo([lead]), complemento([to, a, model, for, how, a, master, developmental, regulator, relocalizes, a, locus, into, a, new, subnuclear, neighborhood, that, is, permissive, for, high, level, transcription, as, an, early, step, in, establishing, a, cell, 'type-specific', genetic, network])]). relacion([sujeto(['These', early, fetal, liver, erythroblasts]), verbo([express]), complemento([predominantly, adult, 'β-globins', and, the, definitive, 'erythroid-specific', transcriptional, modifiers, 'c-myb,', 'Sox6,', and, 'Bcl11A'])]). relacion([sujeto(['Surprisingly,', they, also]), verbo([express]), complemento([low, levels, of, &, 'quot;embryonic"', 'βH1-,', but, not, 'εy-,', globin, transcripts])]). relacion([sujeto(['Consistent', with, these, 'results,', 'RNA', polymerase, and, highly, modified, histones, are]), verbo([found]), complemento([associated, with, 'βH1-', and, adult, 'globin,', but, not, 'εy-globin,', genes])]). relacion([sujeto([5, definitive, proerythroblasts, from, mice, transgenic, for, the, human, 'β-globin', 'locus,', like, human, fetal, 'erythroblasts,']), verbo([express]), complemento([predominately, human, 'γ-,', low, 'β-,', and, no, 'ε-globin', transcripts])]). relacion([sujeto([5, yolk, 'sac-derived', 'EMPs', cultured, in, vitro]), verbo([have]), complemento([similar, murine, and, human, transgenic, globin, expression, patterns])]). relacion([sujeto(['Later', liver, proerythroblasts]), verbo([express]), complemento([low, levels, of, 'γ-globin,', while, adult, marrow, proerythroblasts, express, only, 'β-globin', transcripts])]). relacion([sujeto(['We', conclude, that, yolk, 'sac-derived', 'EMPs,', the, first, of, 2, origins, of, definitive, 'erythropoiesis,']), verbo([express]), complemento([a, unique, pattern, of, globin, genes, as, they, generate, the, first, definitive, erythrocytes, in, the, liver, of, the, mammalian, embryo])]). relacion([sujeto(['Glucocorticoid', receptor, '(', 'GR)', agonists]), verbo([increase]), complemento([erythropoiesis, in, vivo, and, in, vitro])]). relacion([sujeto(['To', clarify, the, effect, of, the, dominant, negative, 'GRβ', isoform, '(', unable, to]), verbo([bind]), complemento(['STAT-5)', on, 'erythropoiesis,', erythroblast, '(', 'EB)', expansion, cultures, of, mononuclear, cells, from, 18, healthy, '(', 'nondiseased)', donors, '(', 'NDs)', and, 16, patients, with, polycythemia, vera, '(', 'PV)', were, studied])]). relacion([sujeto(['GRβ', was]), verbo([expressed]), complemento([in, all, 'PV', 'EBs', but, only, in, 'EBs', from, 1, 'ND'])]). relacion([sujeto(['Dexamethasone', stimulation, of, 'ND', cultures]), verbo([increased]), complemento([the, number, of, immature, 'EBs', characterized, by, low, 'GATA1', and, 'β-globin', 'expression,', but, 'PV', cultures, generated, great, numbers, of, immature, 'EBs', with, low, levels, of, 'GATA1', and, 'β-globin', irrespective, of, dexamethasone, stimulation])]). relacion([sujeto(['In', 'ND', 'EBs,', 'STAT-5', was, not]), verbo([phosphorylated]), complemento([after, dexamethasone, and, erythropoietin, treatment, and, did, not, form, transcriptionally, active, complexes, with, 'GRα,', whereas, in, 'PV', 'EBs,', 'STAT-5', was, constitutively, 'phosphorylated,', but, the, formation, of, 'GR/STAT-5', complexes, was, prevented, by, expression, of, 'GRβ'])]). relacion([sujeto(['These', data, indicate, that, 'GRβ', expression, and, the, presence, of, 'A3669G', likely, contribute, to, development, of, erythrocytosis, in, 'PV', and]), verbo([provide]), complemento([a, potential, target, for, identification, of, novel, therapeutic, agents])]). relacion([sujeto(['Steroid', hormone, biosynthesis]), verbo([requires]), complemento([the, steroidogenic, acute, regulatory, protein, '(', 'STAR)'])]). relacion([sujeto(['Several', transcription, factors]), verbo([participate]), complemento([to, direct, the, proper, spatiotemporal, and, hormonal, regulation, of, the, 'Star', gene, in, 'Leydig', cells])]). relacion([sujeto(['Mechanistically,', this, is, believed, to]), verbo([involve]), complemento([the, functional, interplay, between, many, of, these, factors])]). relacion([sujeto(['Here', we]), verbo([report]), complemento([a, novel, transcriptional, cooperation, between, 'GATA', factors, and, cJUN, on, the, mouse, 'Star', and, human, 'STAR', promoters, in, 'MA-10', 'Leydig', cells])]). relacion([sujeto(['GATA/cJUN', transcriptional, cooperation, on, the, 'Star', promoter, is]), verbo([mediated]), complemento([via, closely, juxtaposed, 'GATA', and, 'AP-1', binding, motifs])]). relacion([sujeto(['Mutation', of, all, functional, 'GATA', and, cJUN, elements, abolished, 'GATA/cJUN', 'cooperation,', which, is, in, agreement, with, previous, data]), verbo([reporting]), complemento([a, direct, interaction, between, 'GATA4', and, cJUN, in, a, heterologous, system])]). relacion([sujeto(['In', this, 'study,', we]), verbo([have]), complemento([systematically, tested, this, paradigm, in, 'blood-producing', populations, in, zebrafish, 'embryos,', including, the, haematopoietic, stem, cells, '(', 'HSCs),', and, found, that, it, takes, a, different, form, in, each, population])]). relacion([sujeto(['In', 'addition,', we]), verbo([have]), complemento([added, a, third, member, to, this, regulatory, 'kernel,', tif1γ, '(', transcription, intermediate, 'factor-1γ)'])]). relacion([sujeto(['We', show, that, tif1γ]), verbo([modulates]), complemento([the, erythroid, versus, myeloid, fate, outcomes, from, 'HSCs', by, differentially, controlling, the, levels, of, gata1, and, pu])]). relacion([sujeto(['By', 'contrast,', tif1γ, positively]), verbo([regulates]), complemento([both, gata1, and, pu])]). relacion([sujeto([1, paradigm, for, lineage, decisions, takes, different, forms, in, different, cellular, contexts, and, is]), verbo([modulated]), complemento([by, tif1γ])]). relacion([sujeto(['Mast', cells, constitutively]), verbo([express]), complemento(['Notch1', and, 'Notch2', on, the, cell, surface])]). relacion([sujeto(['Notch', ligand, 'Dll1', '(', 'Delta-like', 1, ')', stimulation]), verbo([induces]), complemento(['MHC', class, 'II', expression, in, mast, cells, and, renders, them, as, 'antigen-presenting', cells])]). relacion([sujeto(['However,', nothing, is, known, about, the, mechanism, by, which, 'Notch', signaling]), verbo([induces]), complemento(['MHC', class, 'II', expression, in, mast, cells])]). relacion([sujeto(['MHC', class, 'II', genes, are]), verbo([regulated]), complemento([by, the, class, 'II', transactivator, '(', 'CIITA)'])]). relacion([sujeto(['Here,', we, show, that, 'CIITA', expression]), verbo([induced]), complemento([by, 'Dll1', stimulation, in, mouse, bone, 'marrow-derived', mast, cells, '(', 'BMMCs)', depends, critically, on, the, signal, mediated, by, 'Notch1', and, that, the, most, dominant, promoter, in, 'Notch', 'signaling-mediated', 'CIITA', expression, in, 'BMMCs', is, 'pIII,', which, is, a, lymphoid, 'lineage-specific', promoter])]). relacion([sujeto(['ChIP', assays, indicated, that, 'Notch', signaling]), verbo([increased]), complemento([the, binding, of, the, transcription, factor, 'PU'])]). relacion([sujeto([1, expression, using, a, specific, siRNA]), verbo([suppressed]), complemento(['Notch', 'signaling-mediated', 'CIITA', 'expression,', suggesting, that, 'PU'])]). relacion([sujeto([1, contributes, to, the, expression, of, 'MHC', class, 'II']), verbo([induced]), complemento([by, 'Notch', signaling, in, mast, cells])]). relacion([sujeto(['Furthermore,', we, show, that, a, portion, of, freshly, isolated, splenic, mast, cells]), verbo([express]), complemento(['MHC', class, 'II', and, that, the, most, dominant, promoter, of, 'CIITA', in, mast, cells, is, pIII])]). relacion([sujeto(['We']), verbo([have]), complemento([previously, shown, that, neonatal, megakaryocyte, '(', 'MK)', progenitors, are, hyperproliferative, and, give, rise, to, 'MKs', smaller, and, of, lower, ploidy, than, adult, 'MKs'])]). relacion([sujeto(['Based', on, these, 'characteristics,', neonatal, 'MKs']), verbo([have]), complemento([been, considered, immature])]). relacion([sujeto(['This', pattern, is]), verbo([associated]), complemento([with, 'up-regulated', thrombopoietin, '(', 'TPO)', signaling, through, mammalian, target, of, rapamycin, '(', 'mTOR)', and, elevated, levels, of, 'full-length', 'GATA-1', and, its, targets])]). relacion([sujeto(['Blocking', of, mTOR, with, rapamycin]), verbo([suppressed]), complemento([the, maturation, of, neonatal, 'MKs', without, affecting, 'ploidy,', in, contrast, to, the, synchronous, inhibition, of, polyploidization, and, cytoplasmic, maturation, in, adult, 'MKs'])]). relacion([sujeto(['We', propose, that, these, mechanisms, allow, 'fetuses/neonates', to, populate, their, rapidly, expanding, bone, marrow, and, intravascular, spaces, while]), verbo([maintaining]), complemento([normal, platelet, 'counts,', but, also, set, the, stage, for, disorders, restricted, to, 'fetal/neonatal', 'MK', 'progenitors,', including, the, 'Down', 'syndrome-transient', myeloproliferative, disorder, and, the, thrombocytopenia, absent, radius, syndrome])]). relacion([sujeto(['To']), verbo([report]), complemento([clinical, experiences, and, cytogenetic, findings, of, transient, myeloproliferative, disorder, '(', 'TMD)', in, neonates, with, and, without, 'Down', syndrome, '(', 'DS)'])]). relacion([sujeto(['Three', other, patients]), verbo([have]), complemento([not, developed, true, leukemia, after, 'follow-up', of, 8, ',', 9, ',', and, 70, 'months,', respectively])]). relacion([sujeto(['The', transcription, factor, 'GATA1']), verbo([regulates]), complemento([multiple, genes, in, erythroid, lineage, cells])]). relacion([sujeto(['However,', the, means, by, which, 'GATA1']), verbo([regulates]), complemento([the, expression, of, target, genes, during, erythropoiesis, remains, to, be, elucidated])]). relacion([sujeto(['Three', mechanisms]), verbo([have]), complemento([been, postulated, for, the, regulation, of, genes, by, 'GATA1'])]). relacion([sujeto(['First,', individual]), verbo([target]), complemento([genes, may, have, multiple, discrete, thresholds, for, cellular, 'GATA1'])]). relacion([sujeto(['GATA1']), verbo([has]), complemento([a, dynamic, expression, profile, during, 'erythropoiesis,', thus, the, expression, of, a, set, of, 'GATA1', target, genes, may, be, triggered, at, a, given, stage, of, differentiation, by, cellular, 'GATA1'])]). relacion([sujeto(['Second,', the, expression, of, 'GATA1']), verbo([target]), complemento([genes, may, be, 'modified,', at, least, in, 'part,', by, 'GATA2', occupying, the, 'GATA-binding', motifs])]). relacion([sujeto(['GATA2', is]), verbo([expressed]), complemento([earlier, in, erythropoiesis, than, 'GATA1,', and, prior, 'GATA2', binding, may, afford, 'GATA1', access, to, 'GATA', motifs, through, epigenetic, remodeling, and, thus, facilitate, target, gene, expression])]). relacion([sujeto(['Third,', other, regulatory, molecules, specific, to, each]), verbo([target]), complemento([gene, may, function, cooperatively, with, 'GATA1'])]). relacion([sujeto(['If', 'GATA1', is]), verbo([required]), complemento([for, the, expression, of, such, 'cofactors,', a, regulatory, network, will, be, formed, and, relevant, gene, expression, will, be, delayed])]). relacion([sujeto(['IL-1R', antagonist, '(', 'IL-1Ra)', is]), verbo([required]), complemento([for, adequate, host, defense, in, invasive, pneumococcal, disease, '(', 'IPD)'])]). relacion([sujeto(['The', minor, allele, of, an, 'IL1RN', gene, '(', 'C/T)', promoter, polymorphism, '(', 'rs4251961)']), verbo([has]), complemento([been, shown, to, be, associated, with, decreased, 'IL-1Ra', production, in, healthy, adults])]). relacion([sujeto(['Plasma', 'IL-1Ra', concentrations, were, significantly, higher, in, nonsurvivors, compared, with, survivors, '(', p, &, 'lt;', 0.0005, ')', ',', and, the, 'C', allele, of, rs4251961, was]), verbo([associated]), complemento([with, a, significant, increase, in, plasma, 'IL-1Ra', concentrations, '(', p, =, 0.01, ')', during, the, acute, illness, of, 'IPD'])]). relacion([sujeto(['Functional', analyses, demonstrated, that, the, activity, of, the, promoter, constructs, containing, the, 'T', allele]), verbo([increased]), complemento(['~6-fold', as, compared, with, basal, 'activity,', and, that, containing, the, 'C', allele, by, '~9-fold', '(', p, &, 'lt;', 0.001, ')', in, the, presence, of, 'GATA-1'])]). relacion([sujeto(['Our', findings]), verbo([suggest]), complemento([that, the, 'IL-1Ra', 'single-nucleotide', polymorphism, rs4251961, plays, a, key, role, in, the, pathophysiology, of, 'IPD', and, in, other, human, infections])]). relacion([sujeto(['Using', knockdowns, with, morpholinos, and, cell, sorting, analysis, in, transgenic, zebrafish, 'embryos,', we, show, that, 'GATA-1', directly]), verbo([regulates]), complemento([the, expression, of, 'Mfrn1'])]). relacion([sujeto(['Mutagenesis', of, individual, 'GATA-1']), verbo([binding]), complemento([cis, elements, '(', 'GBE)', demonstrated, that, at, least, two, of, the, three, 'GBE', within, this, 'CRM', are, functionally, required, for, 'GATA-mediated', transcription, of, 'Mfrn1'])]). relacion([sujeto(['Our', results]), verbo([provide]), complemento([new, insights, into, the, genetic, regulation, of, mitochondrial, function, and, iron, homeostasis, 'and,', more, 'generally,', illustrate, the, utility, of, 'genome-wide', 'ChIP', analysis, combined, with, zebrafish, transgenesis, for, identifying, 'long-range', transcriptional, enhancers, that, regulate, tissue, development])]). relacion([sujeto(['Ikaros', is]), verbo([associated]), complemento([with, both, gene, transcriptional, activation, and, repression, in, lymphocytes])]). relacion([sujeto(['Ikaros']), verbo([acts]), complemento([also, as, repressor, of, human, 'γ-globin', '(', 'huγ-)', gene, transcription, in, fetal, and, adult, erythroid, cells])]). relacion([sujeto(['Molecular', analysis, in, primary, cells, revealed, that, 'Ikaros']), verbo([interacts]), complemento([with, 'Gata-1', and, favors, 'Brg1', recruitment, to, the, human, 'β-globin', 'Locus', 'Control', 'Region', and, the, 'huγ-promoters,', supporting, 'long-range', chromatin, interactions, between, these, regions])]). relacion([sujeto(['Additionally,', we, demonstrate, that, 'Ikaros', contributes, to, transcription, initiation, and, elongation, of, the, 'huγ-genes,', since, it, is, not, only]), verbo([required]), complemento([for, 'TBP', and, 'RNA', 'Polymerase', 'II', '(', 'Pol', 'II)', assembly, at, the, 'huγ-promoters', but, also, for, conversion, of, 'Pol', 'II', into, the, 'elongation-competent', phosphorylated, form])]). relacion([sujeto(['In', agreement, with, the, 'latter,', we, show, that, 'Ikaros']), verbo([interacts]), complemento([with, 'Cyclin-dependent', kinase, 9, '(', 'Cdk9),', which, contributes, to, efficient, transcription, elongation, by, phosphorylating, the, 'C-terminal', domain, of, the, large, subunit, of, 'Pol', 'II', on, 'Serine', 2, ',', and, favours, 'Cdk9', recruitment, to, 'huγ-promoters'])]). relacion([sujeto(['Our', results, show, that, 'Ikaros', exerts, dual, functionality, during, gene, 'activation,', by]), verbo([promoting]), complemento([efficient, transcription, initiation, and, elongation])]). relacion([sujeto(['To', investigate, whether, 'α-hemoglobin', stabilizing, protein, '(', 'AHSP),', the, 'α-globin-specific', molecular, 'chaperone,', is]), verbo([regulated]), complemento([by, erythroid, transcription, factor, 'NF-E2'])]). relacion([sujeto(['Western', 'blot,', 'real-time', polymerase, chain, 'reaction,', and, chromatin, immunoprecipitation, '(', 'ChIP)', analysis, were, performed, to, detect, the, expression, of, 'AHSP,', the, histone, modifications, at, 'AHSP', gene, 'locus,', and, the]), verbo([binding]), complemento([of, 'GATA-1', at, the, 'AHSP', promoter, with, 'NF-E2p45', deficiency])]). relacion([sujeto(['ChIP', was, also, carried, out, in, dimethyl, sulfoxide, '(', 'DMSO)-induced', 'DS19', cells, and, 'estrogen-induced', 'G1E-ER4', cells, to, examine, 'NF-E2']), verbo([binding]), complemento([to, the, 'AHSP', gene, locus, and, its, changes, during, cell, erythroid, differentiation])]). relacion([sujeto(['We']), verbo([found]), complemento([that, 'AHSP', expression, was, highly, dependent, on, 'NF-E2p45'])]). relacion([sujeto(['NF-E2']), verbo([bound]), complemento([to, the, regions, across, 'AHSP', gene, locus, in, 'vivo,', and, the, transcription, of, 'AHSP', was, transactivated, by, exogenous, 'NF-E2p45'])]). relacion([sujeto(['In', 'addition,', we, observed, the]), verbo([decrease]), complemento([of, 'H3K4', trimethylation, and, 'GATA-1', occupancy, at, the, 'AHSP', gene, locus, in, 'NF-E2p45-deficient', cells])]). relacion([sujeto(['Restoration', of, 'GATA-1', in, 'G1E-ER4', cells, in, turn]), verbo([led]), complemento([to, increased, 'DNA', binding, of, 'NF-E2p45'])]). relacion([sujeto(['NF-E2', may, play, an, important, role, in, 'AHSP', gene, 'regulation,']), verbo([providing]), complemento([new, insights, into, the, molecular, mechanisms, underlying, the, 'erythroid-specific', expression, of, 'AHSP', as, well, as, new, possibilities, for, 'β-thalassemia', treatment])]). relacion([sujeto(['Hemoglobin', 'A2', '(', 'HbA2,', 'α₂δ₂)', and, fetal, hemoglobin, '(', 'HbF,', 'α₂γ₂)', both]), verbo([inhibit]), complemento([the, polymerization, of, hemoglobin, 'S,', which, results, in, erythrocyte, sickling])]). relacion([sujeto(['In', an, effort, to, 'up-regulate', 'δ-globin', to]), verbo([increase]), complemento(['HbA2', 'expression,', we, created, a, series, of, 'EKLF-GATA1', fusion, constructs, composed, of, the, transactivation, domain, of, 'EKLF', and, the, 'DNA-binding', domain, of, 'GATA1,', and, then, tested, their, effects, on, hemoglobin, expression])]). relacion([sujeto(['EKLF-GATA1', fusion, proteins]), verbo([activated]), complemento(['δ-,', 'γ-,', and, 'β-globin', promoters, in, 'K562', 'cells,', and, significantly, 'up-regulated', 'δ-', and, 'γ-globin', 'RNA', transcript, and, protein, expression, in, 'K562', 'and/or', 'CD34(+)', cells])]). relacion([sujeto(['The']), verbo([binding]), complemento([of, 'EKLF-GATA1', fusion, proteins, at, the, 'GATA1', consensus, site, in, the, 'δ-globin', promoter, was, confirmed, by, chromatin, immunoprecipitation, assay])]). relacion([sujeto(['Our', studies, demonstrate, that, 'EKLF-GATA1', fusion, proteins, can]), verbo([enhance]), complemento(['δ-globin', expression, through, interaction, with, the, 'δ-globin', 'promoter,', and, may, represent, a, new, genetic, therapeutic, approach, to, 'β-hemoglobinopathies'])]). relacion([sujeto(['The', protein, levels]), verbo([expressed]), complemento([by, these, genes, are, thought, to, be, regulated, by, a, 'self-excitatory', feedback, loop, for, each, gene, and, a, 'cross-inhibitory', feedback, loop, between, the, two, genes])]). relacion([sujeto(['A', mathematical, model, that, captures, the, dynamical, interaction, between, these, two, genes]), verbo([reveals]), complemento([that, constant, levels, of, 'self-excitation', and, 'cross-inhibition', allow, the, most, 'self-exciting', or, 'cross-inhibiting', gene, to, dominate, the, system])]). relacion([sujeto(['These', 'time-dependent', parameters]), verbo([lead]), complemento([to, new, 'phenomena,', including, the, development, of, new, limit, cycles, and, basins, of, attraction])]). relacion([sujeto(['Our', findings]), verbo([suggest]), complemento([that, even, small, perturbations, in, the, 'PU'])]). relacion([sujeto(['These', 'time-dependent', parameter, models, may, also]), verbo([have]), complemento([implications, for, other, gene, systems, and, provide, new, ways, to, understand, the, mechanisms, of, cellular, differentiation])]). relacion([sujeto(['Recent', studies]), verbo([have]), complemento([showed, that, transcription, elongation, factors, regulate, early, development])]). relacion([sujeto(['Foggy/Spt5', is, a, subunit, of, 'DRB', 'sensitivity-inducing', 'factor,', which, negatively, and, positively]), verbo([regulates]), complemento([transcription, elongation])]). relacion([sujeto(['Here,', we]), verbo([report]), complemento([that, the, positive, function, of, 'Foggy/Spt5', is, required, for, gata1, expression, during, zebrafish, embryonic, hematopoiesis])]). relacion([sujeto(['Antisense', morpholino, oligonucleotide, '(', 'MO)-mediated', knockdown, of, 'foggy/spt5']), verbo([has]), complemento([led, to, a, reduction, in, the, expression, of, gata1, and, the, gata1, target, genes, alas2, and, hbae3, and, inhibited, proper, hemoglobin, production])]). relacion([sujeto(['By', 'contrast,', expression, of, hematopoietic, stem, cell, and, endothelial, 'markers,', including, 'scl,', 'lmo2,', 'gata2,', 'fli-1,', and, 'flk-1,', and, expression, of, 'biklf,', whose, product, directs, gata1, expression, via, its, direct]), verbo([binding]), complemento([to, the, gata1, 'promoter,', were, 'unaltered,', suggesting, that, gata1, is, a, functionally, important, target, gene, of, 'Foggy/Spt5'])]). relacion([sujeto(['Therefore,', this, study]), verbo([provides]), complemento([evidence, that, 'Foggy/Spt5', plays, an, important, role, in, gata1, gene, expression, and, erythropoiesis, through, its, transcriptional, activation, domain])]). relacion([sujeto(['Microtubules', play, important, roles, in, mitotic, spindle, assembly, and, chromosome, segregation, to]), verbo([maintain]), complemento([normal, cell, cycle, progression])]). relacion([sujeto(['A', number, of, 'microtubule-associated', proteins]), verbo([have]), complemento([been, identified, in, epithelial, and, neural, cell, 'cultures;', 'however,', their, physiological, significance, is, not, well, characterized, due, to, the, lack, of, appropriate, in, vivo, animal, models])]). relacion([sujeto(['Nucleolar', 'spindle-associated', protein, '(', 'NuSAP)', is, a, 'microtubule-binding', protein, and, is]), verbo([reported]), complemento([to, be, involved, in, mitosis, by, cell, culture, studies])]). relacion([sujeto(['Using', in, situ, 'hybridization,', we, demonstrated, that, transcripts, of, zebrafish, nusap1, are, specifically]), verbo([expressed]), complemento([in, the, 'retina,', 'forebrain,', hindbrain, and, neural, crest])]). relacion([sujeto(['Mechanistic', studies, revealed, that, nusap1, morphants]), verbo([have]), complemento([an, altered, expression, pattern, of, neural, crest, markers, crestin, and, 'sox9b,', but, normal, expression, of, blood, vessel, and, notochord, markers, gata1, and, shh])]). relacion([sujeto(['In', 'addition,', nusap1, mRNA, injection]), verbo([caused]), complemento([serious, apoptosis, in, retina, and, hindbrain, 'tissue,', and, these, phenotypes, can, be, rescued, by, 'co-injection', of, morpholino, against, nusap1])]). relacion([sujeto(['These', observations, not, only]), verbo([suggest]), complemento([a, role, for, 'Nusap1', in, connecting, apoptosis, with, cell, 'migration,', but, also, provide, strong, evidences, that, 'Nusap1', is, potentially, involved, in, morphogenesis, in, vertebrates])]). relacion([sujeto(['Notch', signaling, is, an, evolutionarily]), verbo([conserved]), complemento([regulatory, circuitry, implicated, in, cell, fate, determination, in, various, developmental, processes, including, hematopoietic, stem, cell, 'self-renewal', and, differentiation, of, blood, lineages])]). relacion([sujeto(['Known', endogenous, inhibitors, of, 'Notch', activity, are, 'Numb-Nb', and, 'Numblike-Nbl,', which, play, partially, redundant, functions, in, specifying, and]), verbo([maintaining]), complemento([neuronal, differentiation])]). relacion([sujeto(['Nb', and, 'Nbl', are]), verbo([expressed]), complemento([in, most, tissues, including, embryonic, and, adult, hematopoietic, tissues, in, mice, and, 'humans,', suggesting, possible, roles, for, these, proteins, in, hematopoiesis])]). relacion([sujeto(['Our', results, indicate, that, 'Notch', activity, is]), verbo([increased]), complemento([in, embryos, injected, with, 'nb/nbl', 'morpholino,', and, we, show, that, inhibition, of, 'Notch', activation, can, partially, rescue, the, hematopoietic, phenotype])]). relacion([sujeto(['Our', results]), verbo([provide]), complemento([the, first, in, vivo, evidence, of, an, involvement, of, 'Numb', and, 'Numblike', in, zebrafish, erythroid, differentiation, during, primitive, hematopoiesis])]). relacion([sujeto(['Furthermore,', we]), verbo([found]), complemento(['that,', at, least, in, 'part,', the, 'nb/nbl', morphant, phenotype, is, due, to, enhanced, 'Notch', activation, within, hematopoietic, 'districts,', which, in, turn, results, in, primitive, erythroid, differentiation, defects])]). relacion([sujeto(['We', show, here, that, 'HoxA3,', a, gene, uniquely]), verbo([expressed]), complemento([in, the, embryonic, but, not, yolk, sac, 'vasculature,', restrains, haematopoietic, differentiation, of, the, earliest, endothelial, 'progenitors,', and, induces, reversion, of, the, earliest, haematopoietic, progenitors, into, 'CD41-negative', endothelial, cells])]). relacion([sujeto(['This', reversible, modulation, of, 'endothelial-haematopoietic', state, is, accomplished, by]), verbo([targeting]), complemento([key, haematopoietic, transcription, factors, for, 'downregulation,', including, 'Runx1,', 'Gata1,', 'Gfi1B,', 'Ikaros,', and, 'PU'])]). relacion([sujeto(['Through', 'loss-of-function,', and, 'gain-of-function', epistasis, 'experiments,', and, the, identification, of, antipodally]), verbo([regulated]), complemento(['targets,', we, show, that, among, these, 'factors,', 'Runx1', is, uniquely, able, to, erase, the, endothelial, program, set, up, by, 'HoxA3'])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([both, why, a, frank, endothelium, does, not, precede, haematopoiesis, in, the, yolk, 'sac,', and, why, haematopoietic, stem, cell, generation, requires, 'Runx1', expression, only, in, endothelial, cells])]). relacion([sujeto(['Furthermore,', expression, of, 2, 'HG-producing', 'IDH', alleles, in, cells]), verbo([induced]), complemento([global, 'DNA', hypermethylation])]). relacion([sujeto(['In', the, 'AML', 'cohort,', 'IDH1/2', mutations, were, mutually, exclusive, with, mutations, in, the, 'α-ketoglutarate-dependent', enzyme, 'TET2,', and, 'TET2', 'loss-of-function', mutations, were]), verbo([associated]), complemento([with, similar, epigenetic, defects, as, 'IDH1/2', mutants])]). relacion([sujeto(['Finally,', either, expression, of, mutant, 'IDH1/2', or, 'Tet2', depletion, impaired, hematopoietic, differentiation, and]), verbo([increased]), complemento(['stem/progenitor', cell, marker, 'expression,', suggesting, a, shared, proleukemogenic, effect])]). relacion([sujeto(['Activated', leukocyte, cell, adhesion, molecule, '(', 'ALCAM/CD166)', is]), verbo([expressed]), complemento([by, hematopoietic, stem, cells])]). relacion([sujeto(['However,', its, role, in, hematopoietic, differentiation]), verbo([has]), complemento([not, previously, been, defined])]). relacion([sujeto(['In', agreement, with, this, 'finding,', the, 'ALCAM', promoter, is, occupied, by, 'GATA-1', in, 'vivo,', and, a, cognate, motif, at, -, 850]), verbo([inhibited]), complemento([promoter, activity, in, 'K562', and, 'MEG-01', cells])]). relacion([sujeto(['Gain-of-function', studies, showed, that, 'ALCAM', clusters, 'K562', cells, in, a, process, that]), verbo([requires]), complemento(['PKC'])]). relacion([sujeto(['Induction', of, megakaryocytic, differentiation, in, 'K562', clones]), verbo([expressing]), complemento(['ALCAM', activated, 'PKC-δ', and, triggered, apoptosis])]). relacion([sujeto(['Marked', apoptosis, of, 'ALCAM-expressing', 'K562', clones, treated, with, 'PMA']), verbo([suggests]), complemento([that, aberrant, 'ALCAM', expression, in, erythromegakaryocytic, progenitors, may, contribute, to, megakaryocytopenia])]). relacion([sujeto(['Oogenesis', and, primordial, follicle, formation, are, tightly, linked, 'processes,']), verbo([requiring]), complemento([organized, and, precisely, timed, communication, between, somatic, and, germ, cells])]). relacion([sujeto(['Deviations', in, ovarian, cell, cross, 'talk,', or, aberrant, gene, expression, within, one, of, the, cell, 'populations,', can]), verbo([lead]), complemento([to, follicle, loss, or, 'dysfunction,', resulting, in, infertility])]). relacion([sujeto(['Expression', of, 'GATA-like', 'protein-1', '(', 'GLP-1)', in, ovarian, somatic, cells, is]), verbo([required]), complemento([for, normal, fertility, in, female, 'mice,', as, 'GLP-1', deficiency, leads, to, the, absence, of, oocytes, at, birth])]). relacion([sujeto(['However,', the, timing, and, nature, of, this, germ, cell]), verbo([loss]), complemento([is, not, well, understood])]). relacion([sujeto(['In', this, 'study,', we, characterize, the, embryonic, germ, cell]), verbo([loss]), complemento([in, 'GLP-1', null, mice])]). relacion([sujeto(['Quantitative', 'PCR', demonstrates, that, ovarian, 'Glp-1', mRNA, is]), verbo([expressed]), complemento([in, a, bimodal, pattern, during, 'embryogenesis,', peaking, at, 'E13'])]). relacion([sujeto(['In', 'contrast,', adult, ovaries]), verbo([express]), complemento([low, but, detectable, levels, of, 'Glp-1', mRNA])]). relacion([sujeto(['Upon', arrival, at, the, 'gonad,', precocious]), verbo([loss]), complemento([of, germ, cells, begins, at, around, 'E13'])]). relacion([sujeto(['This']), verbo([loss]), complemento([is, completed, by, birth, and, is, accompanied, by, defects, in, the, expression, of, genes, associated, with, meiotic, entry])]). relacion([sujeto(['Interestingly,', somatic, pregranulosa, cells, still, form, basement, membranes, surrounding, germ, line, cysts, and]), verbo([express]), complemento([mRNA, encoding, paracrine, signaling, molecules, that, communicate, with, 'oocytes,', albeit, at, lower, levels, than, normal])]). relacion([sujeto(['Together,', these, data, imply, that, the, somatic, cell, protein, 'GLP-1', is, not, necessary, for, many, pregranulosa, cell, functions, but, is]), verbo([required]), complemento([for, germ, cell, survival])]). relacion([sujeto(['The', 'Gα13b', morphants, 'don\'t', show, complete]), verbo([loss]), complemento([of, expression, of, 'gata1,', pu])]). relacion([sujeto([1, or, flk, until, 35, hpf]), verbo([suggests]), complemento([that, 'Gα13b', is, closely, related, to, the, development, of, hematopoietic, cells])]). relacion([sujeto(['Further', studies]), verbo([reveal]), complemento([that, blood, cells, and, vascular, endothelial, cells, have, undergone, apoptosis, through, a, 'p53-dependent', pathway, in, 'Gα13b-depleted', embryos])]). relacion([sujeto(['Although', several, types, of, histamine, 'H(1)', receptor, antagonist, '(', 'antihistamine)']), verbo([have]), complemento([been, developed, and, used, for, the, treatment, of, allergic, 'diseases,', the, influence, of, antihistamines, on, 'TARC', and, 'MDC', production, is, not, well, understood])]). relacion([sujeto(['CD14+', cells, prepared, from, patients, with, pollinosis, to, 'Japanese', cedar, pollen, were]), verbo([stimulated]), complemento([with, specific, allergen, extracted, from, 'Japanese', cedar, pollen, '(', 'Cry', j, 1, ')', in, the, presence, of, azelastine, '(', 'AZE),', ketotifen, '(', 'KET),', fexofenadine, '(', 'FEX)', and, oxatomide, '(', 'OXA)', for, 6, days])]). relacion([sujeto(['FEX', at, 250, 'ng/ml,', which, is, almost, equal, to, therapeutic, blood, 'levels,']), verbo([caused]), complemento([a, significant, inhibition, of, 'TARC', and, 'MDC', production])]). relacion([sujeto(['However,', 'AZE,', 'OXA', and, 'KET']), verbo([required]), complemento([higher, concentrations, than, their, therapeutic, blood, levels, to, suppress, production, of, these, factors])]). relacion([sujeto(['FEX', at, 250, 'ng/ml', also]), verbo([suppressed]), complemento(['NF-κB', 'activation,', phosphorylation, of, p38, 'MAPK', and, extracellular, 'signal-regulated', kinases, 1, and, 2, and, expression, of, mRNA, for, 'TARC', and, 'MDC'])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, 'antihistamines,', especially, 'FEX,', suppress, 'CC', chemokine, production, from, 'CD14+', cells, through, interference, with, 'antigen-mediated', signaling, and, result, in, favorable, modification, of, allergic, disease, states, or, conditions])]). relacion([sujeto(['A', relatively, small, cadre, of, 'lineage-restricted', transcription, factors, largely, orchestrates, 'erythropoiesis,', but, how, these]), verbo([nuclear]), complemento([factors, interact, to, regulate, this, complex, biology, is, still, largely, unknown])]). relacion([sujeto(['Human', '(', 'h)']), verbo([induced]), complemento([pluripotent, stem, cells, '(', 'iPSCs)', are, a, potentially, abundant, source, of, blood, 'cells,', but, how, best, to, select, iPSC, clones, suitable, for, this, purpose, from, among, the, many, clones, that, can, be, simultaneously, established, from, an, identical, source, is, not, clear])]). relacion([sujeto(['During', 'differentiation,', reduction, of, 'c-MYC', expression, after, initial, reactivation, of, 'c-MYC', expression, in, selected, hiPSC, clones, was]), verbo([associated]), complemento([with, more, efficient, in, vitro, generation, of, 'CD41a(+)CD42b(+)', platelets])]). relacion([sujeto(['In', 'contrast,', sustained, and, excessive, 'c-MYC', expression, in, megakaryocytes, was, accompanied, by]), verbo([increased]), complemento([p14, '(', 'ARF)', and, p16, '(', 'INK4A)', 'expression,', decreased, 'GATA1', 'expression,', and, impaired, production, of, functional, platelets])]). relacion([sujeto(['These', findings]), verbo([suggest]), complemento([that, the, pattern, of, 'c-MYC', 'expression,', particularly, its, later, 'decline,', is, key, to, producing, functional, platelets, from, selected, iPSC, clones])]). relacion([sujeto(['DS', patients, with, 'AML,', and, in, particular, 'AMkL,']), verbo([have]), complemento(['event-free', survival, rates, of, 80, -, 100, '%', in, contrast, to, 'event-free', survival, rates, of, less, than, 35, '%', for, 'non-DS', children, with, 'AMkL'])]). relacion([sujeto(['DS', children, with, acute, lymphoblastic, leukemia]), verbo([have]), complemento([a, more, heterogeneous, 'disease,', with, approximately, 30, '%', of, the, patients, having, somatic, 'JAK2', 'mutations,', heightened, methotrexate, sensitivity, and, higher, rates, of, 'treatment-related', toxicities])]). relacion([sujeto(['We', identified, a, total, of, 368, genes, that, were, differentially]), verbo([expressed]), complemento([in, women, with, preeclampsia, compared, to, normal, controls, with, false, discovery, rate, '(', 'FDR)', controlled, at, 10, '%'])]). relacion([sujeto(['In', follow, up, experiments, we, further, analyzed, the, expression, levels, of, a, number, of, genes, that, were, identified, as, altered, by, the, microarray, data, including, survivin, '(', 'BIRC5),', caveolin, '(', 'CAV1),', 'GATA']), verbo([binding]), complemento(['protein-1', '(', 'GATA1),', signal, tranducer, and, activator, of, transcription, 1, '(', 'STAT1),', 'E2F', transcription, 'factor-1', '(', 'E2F1),', 'fibronectin-1', '(', 'FN1),', 'interleukin-4', '(', 'IL-4),', matrix, 'metalloprotease-9', '(', 'MMP-9)', and, 'WAP', four, disulfide, domain, protein, '(', 'WFDC-1)', by, 'QRTPCR'])]). relacion([sujeto(['We']), verbo([have]), complemento([characterized, the, 'genome-wide', mRNA, expression, changes, associated, with, 'preeclampsia-specific', genes, in, circulating, maternal, blood, cells, at, the, time, of, delivery])]). relacion([sujeto(['In', addition, to]), verbo([providing]), complemento([information, relating, to, the, biological, basis, of, the, preeclampsia, 'phenotype,', our, data, provide, a, number, of, potential, biomarkers, for, use, in, the, further, characterization, of, this, disease])]). relacion([sujeto(['Developmental', control, mechanisms, often, use, multimeric, complexes, containing, transcription, 'factors,', 'coregulators,', and, additional, 'non-DNA']), verbo([binding]), complemento([components])]). relacion([sujeto(['We', analyzed, the, function, of, components, of, a, complex, containing, master, regulators, of, hematopoiesis, '(', 'GATA-1', and, 'Scl/TAL1)', and, the, 'non-DNA']), verbo([binding]), complemento([components, 'ETO2,', the, 'LIM', domain, protein, 'LMO2,', and, the, chromatin, looping, factor, 'LDB1'])]). relacion([sujeto(['Surprisingly,', we, discovered, that, 'ETO2', and, 'LMO2']), verbo([regulate]), complemento([distinct, 'target-gene', ensembles, in, erythroid, cells])]). relacion([sujeto(['ETO2', commonly, repressed, 'GATA-1', function, via]), verbo([suppressing]), complemento([histone, 'H3', 'acetylation,', although, it, also, regulated, methylation, of, histone, 'H3', at, lysine, 27, at, select, loci])]). relacion([sujeto(['Prior', studies, defined, multiple, modes, by, which, 'GATA-1']), verbo([regulates]), complemento([target, genes, with, or, without, the, coregulator, 'Friend', of, 'GATA-1', '(', 'FOG-1)'])]). relacion([sujeto(['As', 'LMO2', controls, 'hematopoiesis,', its, dysregulation, is, 'leukemogenic,', and, its, influence, on, 'GATA', factor, function, is, 'unknown,', this, mechanistic, link]), verbo([has]), complemento([important, biological, and, pathophysiological, implications])]). relacion([sujeto(['The', demonstration, that, 'ETO2', and, 'LMO2', exert, qualitatively, distinct, functions, at, endogenous, loci, illustrates, how, components, of, complexes, containing, master, developmental, regulators, can, impart, the, capacity, to]), verbo([regulate]), complemento([unique, cohorts, of, target, 'genes,', thereby, diversifying, complex, function])]). relacion([sujeto(['The', most, common, translocation, in, childhood, 'T-cell', acute, lymphoblastic, leukemia, '(', 'T-ALL)']), verbo([involves]), complemento([the, 'LMO2', 'locus,', resulting, in, ectopic, expression, of, the, 'LMO2', gene, in, human, thymocytes])]). relacion([sujeto(['The', 'LMO2', gene, was, also]), verbo([activated]), complemento([in, patients, with, 'X-linked', 'Severe', 'Combined', 'Immune', 'Deficiency', treated, with, gene, therapy, because, of, retroviral, insertion, in, the, 'LMO2', locus])]). relacion([sujeto(['The', 'LIM', '(', 'Lin', 11, ',', 'Isl-1,', 'Mec-3)', domain, containing, 'LMO2', protein]), verbo([regulates]), complemento([erythropoiesis, as, part, of, a, large, transcriptional, complex, consisting, of, 'LMO2,', 'TAL1,', 'E47,', 'GATA1', and, 'LDB1', that, recognizes, bipartite, 'E-box-GATA1', sites, on, target, genes])]). relacion([sujeto(['To', address, the, 'mechanism(s)', of, 'Tal1/Lmo2', synergy, in, 'leukemia,', we, generated, 'Lmo2', transgenic, mice, and, mated, them, with, mice, that]), verbo([express]), complemento(['wild-type', 'Tal1', or, a, 'DNA-binding', mutant, of, 'TAL1'])]). relacion([sujeto(['These', data, demonstrate, that, the, 'DNA-binding', activity, of, 'Tal1', is, not]), verbo([required]), complemento([to, cooperate, with, 'Lmo2', to, cause, leukemia, in, mice, and, suggest, that, 'Lmo2', may, cooperate, with, 'Tal1', to, interfere, with, 'E47/HEB', 'function(s)'])]). relacion([sujeto(['Using', antisense, morpholino, oligomers, to, interrupt, meis1, expression, we]), verbo([found]), complemento(['that,', although, primitive, macrophage, development, could, occur, 'unhampered,', posterior, erythroid, differentiation, required, 'meis1,', and, its, absence, resulted, in, a, severe, decrease, in, the, number, of, mature, erythrocytes])]). relacion([sujeto(['In', 'addition,', meis1, morpholino, 'knock-down']), verbo([led]), complemento([to, dramatic, single, arteriovenous, tube, formation])]). relacion([sujeto(['We', also]), verbo([found]), complemento([that, 'knock-down', of, pbx1, resulted, in, a, phenotype, that, was, strikingly, similar, to, that, of, meis1, 'knock-down', zebrafish])]). relacion([sujeto(['These', results, imply, that, 'meis1,', jointly, with, 'pbx1,']), verbo([regulates]), complemento([primitive, hematopoiesis, as, well, as, vascular, development])]). relacion([sujeto(['In', the, present, study, we]), verbo([provide]), complemento([evidence, that, 'CDDO-Im', exerts, in, vitro, a, potent, inhibitory, effect, on, erythroid, cell, proliferation, and, survival, and, a, stimulatory, action, on, megakaryocytic, differentiation])]). relacion([sujeto(['The', effect, of, 'CDDO-Im', on, erythroid, and, megakaryocytic, differentiation, was, evaluated, both, on, normal, hemopoietic, progenitor, cells, '(', 'HPCs)']), verbo([induced]), complemento([to, selective, erythroid, '(', 'E)', or, megakaryocytic, '(', 'Mk)', differentiation, and, on, erythroleukemic, cell, lines, 'HEL', and, 'TF1'])]). relacion([sujeto(['Among', the, 259, and, 511, altered, transcripts, at, both, 'concentrations,', 'respectively,', the, expressions, of, genes]), verbo([involved]), complemento([in, the, circadian, rhythm, were, further, investigated])]). relacion([sujeto(['Angiogenesis', was, analyzed, in, 'double-transgenic', zebrafish, embryos, 'Tg(fli1a:EGFP)y1;Tg(gata1:dsRed)sd2;', no, major, defects, were]), verbo([induced]), complemento([by, 'PKC412', treatment, at, both, concentrations])]). relacion([sujeto(['Apoptosis', occurred, in, olfactory, placodes, of, embryos, exposed, to, 40, 'μg/l,', and, 'DNA', damage, was]), verbo([induced]), complemento([at, both, 'PKC412', concentrations])]). relacion([sujeto(['This', study]), verbo([leads]), complemento([to, the, conclusion, that, 'PKC412-induced', alterations, of, gene, transcripts, are, partly, paralleled, by, physiological, effects, at, 'high,', but, not, at, low, 'PKC412', concentrations, expected, to, be, of, environmental, relevance])]). relacion([sujeto(['Although', aldehyde, dehydrogenase, '(', 'ALDH)', activity]), verbo([has]), complemento([become, a, surrogate, of, hematopoietic, stem, and, progenitor, cells, '(', 'HSPCs),', its, function, during, hematopoiesis, was, unclear])]). relacion([sujeto(['MOs']), verbo([targeting]), complemento([aldhs, were, injected, between, 1, and, 4, -, cell, stage])]). relacion([sujeto(['DEAB', treatment, between, 0, and, 18, hpf]), verbo([increased]), complemento([gene, expression, associated, with, 'HSPC', '(', 'scl,', 'lmo2),', erythropoiesis, '(', 'gata1,', 'α-', and, 'β-eHb)', and, myelopoiesis, '(', 'spi1)', as, well, as, 'gfp(+)', cells, in, dissociated, 'Tg(gata1:gfp)', embryos])]). relacion([sujeto(['In', 'all,', 14, out, of, 15, zebrafish, aldhs, were, detectable, by, reverse, transcription, 'PCR', in, 18, hpf, 'embryos,', of, which, only, aldh1a2, and, aldh16a1, were]), verbo([expressed]), complemento([in, sites, pertinent, to, hematopoiesis])]). relacion([sujeto(['Molecular']), verbo([targeting]), complemento([by, 'MOs', was, demonstrated, for, 15, 'aldhs,', but, none, of, 'them,', even, in, combined, aldh1a2, and, aldh1a3, 'knockdown,', recapitulated, the, hematopoietic, expansion, in, 'DEAB-treated', embryos])]). relacion([sujeto(['The', transcriptional, regulator, 'GATA1', is, crucially]), verbo([involved]), complemento([in, megakaryocytopoiesis, and, erythropoiesis])]). relacion([sujeto(['Mutations', of, the, gene, which, is, located, on, the, 'X', chromosome]), verbo([have]), complemento([been, associated, with, platelet, and, red, blood, cell, abnormalities])]). relacion([sujeto(['We', identified, a, family, with, a, 'GATA1', '(', 'G208R)', mutation, in, whom, a, low, male, birth, rate, and, frequent, miscarriages, among, heterozygous, females]), verbo([suggested]), complemento([increased, fetal, death, in, male, hemizygotes])]). relacion([sujeto(['Platelets', were, 'dimorphous,', and, thrombocytopenia, was]), verbo([associated]), complemento([with, erythroblastosis])]). relacion([sujeto(['Survivin', is, an, inhibitor, of, apoptosis, protein, family, member, that]), verbo([has]), complemento([an, essential, role, in, cellular, proliferation, as, a, component, of, the, chromosome, passenger, complex])]). relacion([sujeto(['Survivin', is, highly]), verbo([expressed]), complemento([in, embryos, and, in, proliferating, adult, 'tissues,', but, it, is, not, expressed, in, most, differentiated, cells])]). relacion([sujeto(['Although', many, studies]), verbo([have]), complemento([shown, that, survivin, is, required, for, cancer, 'cells,', the, extent, to, which, survivin, contributes, to, the, initiation, of, tumors, is, unknown])]). relacion([sujeto(['Here', we, show, that, transgenic, mice, that, overexpress, survivin, in, hematopoietic, cells, are, at, an]), verbo([increased]), complemento([risk, of, hematologic, tumors])]). relacion([sujeto(['We', conclude, that, survivin, may]), verbo([promote]), complemento([tumorigenesis, by, imparting, a, survival, advantage, to, cells, that, acquire, additional, genetic, lesions])]). relacion([sujeto(['In', most, 'cases,', transient, myeloproliferative, disorders]), verbo([require]), complemento([no, 'treatment,', while, acute, megakaryoblastic, leukaemia, of, 'Down\'s', syndrome, is, characterised, by, an, increased, sensitivity, to, chemotherapy, and, its, treatment, should, be, adapted, with, a, reduction, in, dose, intensity])]). relacion([sujeto(['We']), verbo([found]), complemento([abnormal, 'GATA1', mutated, clones, in, each, 'case,', and, a, specific, point, mutation, at, exón, 2, was, detected, in, three, cases])]). relacion([sujeto(['We', conclude, that, 'GATA1', mutational, study, is, a, useful, tool, for, the, diagnosis, and, management, of, trisomy, 21]), verbo([associated]), complemento([myeloproliferative, disorders])]). relacion([sujeto(['The', patient, received, three, courses, of, chemotherapy]), verbo([leading]), complemento([to, complete, remission])]). relacion([sujeto(['This', case, emphasizes, the, significance, of, trisomy, 21, as, the]), verbo([cause]), complemento([of, transient, abnormal, myelopoiesis, in, 'Down', syndrome])]). relacion([sujeto(['Gene', regulation, commonly]), verbo([involves]), complemento([interaction, among, 'DNA,', proteins, and, biochemical, conditions])]). relacion([sujeto(['Computational', methods, that, detect, weak, 'protein-binding', signals, and, simultaneously]), verbo([maintain]), complemento([a, high, specificity, yet, remain, to, be, challenging])]). relacion([sujeto(['We', call, the, additional, data, related, with, the]), verbo([target]), complemento([protein, binding, as, supporting, tracks])]). relacion([sujeto(['We', demonstrate, that, utilizing, biologically, related, information, can, significantly]), verbo([increase]), complemento([the, discovery, of, true, 'protein-binding', 'sites,', while, still, maintaining, a, desired, level, of, false, positive, calls])]). relacion([sujeto(['To', dissect, the, roles, of, functional, domains, in, 'Fli1,', we, recently, generated, mutant, 'Fli1', mice, that]), verbo([express]), complemento([a, truncated, 'Fli1', protein, '(', 'Fli1(ΔCTA))', that, lacks, the, 'carboxy-terminal', regulatory, '(', 'CTA)', domain])]). relacion([sujeto(['Heterozygous', 'Fli1(ΔCTA)', mice, are, 'viable,', while, homozygous, mice]), verbo([have]), complemento([reduced, viability])]). relacion([sujeto(['The', peripheral, blood, of, these, viable, 'Fli1(ΔCTA)/Fli1(ΔCTA)', homozygous, mice]), verbo([has]), complemento([reduced, platelet, numbers])]). relacion([sujeto(['Analysis', of, mRNA, from, total, bone, marrow, and, purified, megakaryocytes, from, 'Fli1(ΔCTA)/Fli1(ΔCTA)', mice, revealed, downregulation, of, genes]), verbo([associated]), complemento([with, megakaroyctic, 'development,', including, 'c-mpl,', 'gpIIb,', 'gpIV,', 'gpIX,', 'PF4,', 'NF-E2,', 'MafG,', and, 'Rab27B'])]). relacion([sujeto(['While', 'Fli1', and, 'GATA-1', synergistically]), verbo([regulate]), complemento([the, expression, of, multiple, megakaryocytic, 'genes,', the, level, of, 'GATA-1', present, on, a, subset, of, these, promoters, is, reduced, in, vivo, in, the, 'Fli1(ΔCTA)/Fli1(ΔCTA)', 'mice,', providing, a, possible, mechanism, for, the, impared, transcription, observed])]). relacion([sujeto(['Collectively,', these, data, showed, for, the, first, time, a, hemostatic, defect]), verbo([associated]), complemento([with, the, loss, of, a, specific, functional, domain, of, the, transcription, factor, 'Fli1', and, suggest, previously, unknown, in, vivo, roles, in, megakaryocytic, cell, differentiation])]). relacion([sujeto(['However,', there, are, no]), verbo([reports]), complemento([on, the, expression, levels, of, 'GATA1s', in, 'TAM', 'blasts,', and, the, risk, factors, for, the, progression, to, 'ML-DS', are, unidentified])]). relacion([sujeto(['Phenotypic', analyses, of, 66, 'TAM', patients, with, 'GATA1', mutations, revealed, that, 'GATA1s', low, mutations, were, significantly]), verbo([associated]), complemento([with, a, risk, of, progression, to, 'ML-DS', '(', 'P', &, 'lt;'])]). relacion([sujeto(['Our', study, indicates, that, quantitative, differences, in, mutant, protein, levels]), verbo([have]), complemento([significant, effects, on, the, phenotype, of, 'TAM', and, warrants, further, investigation, in, a, prospective, study])]). relacion([sujeto(['FlnA(loxP/y)', 'GATA1-Cre', males]), verbo([have]), complemento([a, macrothrombocytopenia, and, increased, tail, bleeding, times])]). relacion([sujeto(['FlnA-null', platelets]), verbo([have]), complemento([decreased, expression, and, altered, surface, distribution, of, 'GPIbalpha', because, they, lack, the, normal, cytoskeletal, linkage, of, 'GPIbalpha', to, underlying, actin, filaments])]). relacion([sujeto(['FlnA-null', platelets, fail, to, spread, and]), verbo([have]), complemento([decreased, 'alpha-granule', 'secretion,', integrin, alphaIIbbeta3, 'activation,', and, protein, tyrosine, 'phosphorylation,', particularly, that, of, the, protein, tyrosine, kinase, 'Syk', and, phospholipase, 'C-gamma2,', in, response, to, stimulation, through, the, collagen, receptor, 'GPVI', and, the, 'C-type', 'lectin-like', receptor, 2])]). relacion([sujeto(['This', signaling, defect, was, traced, to, the]), verbo([loss]), complemento([of, a, novel, 'FlnA-Syk', 'interaction,', as, 'Syk', binds, to, 'FlnA', at, 'immunoglobulin-like', repeat, 5])]). relacion([sujeto(['Our', findings]), verbo([reveal]), complemento([that, the, interaction, between, 'FlnA', and, 'Syk', regulates, 'ITAM-', and, 'ITAM-like-containing', receptor, signaling, and, platelet, function])]). relacion([sujeto(['These']), verbo([have]), complemento([led, to, the, discovery, of, previously, unknown, players, in, 'hematopoiesis,', as, well, as, helped, our, understanding, of, hematopoietic, development])]). relacion([sujeto(['In', this, 'review,', we, will, summarize, hematopoiesis, in, the, zebrafish, and, discuss, how, genetic, approaches, using, the, zebrafish, system]), verbo([have]), complemento([helped, to, build, our, current, knowledge, in, the, field, of, hematopoiesis])]). relacion([sujeto(['These', precursors, undergo, progressive, maturation, in, the, 'bloodstream,', characterized, by]), verbo([nuclear]), complemento([condensation, and, embryonic, hemoglobin, accumulation])]). relacion([sujeto(['Targeted', disruption, of, genes, in, the, mouse, that, result, in, failure, of, the, emergence, or, maturation, of, the, primitive, erythroid, lineage]), verbo([leads]), complemento([to, early, fetal, 'death,', indicating, that, the, primitive, erythroid, lineage, is, necessary, for, survival, of, the, mammalian, embryo])]). relacion([sujeto(['While', it, was, thought, for, over, a, century, that, primitive, erythroid, cells, were, uniquely, nucleated, mammalian, red, 'cells,', it, is, now]), verbo([recognized]), complemento([that, 'they,', like, their, definitive, erythroid, 'counterparts,', enucleate, to, form, reticulocytes, and, pyrenocytes])]). relacion([sujeto(['This', surprising]), verbo([finding]), complemento([indicates, that, the, primitive, erythroid, lineage, is, indeed, 'mammalian,', rather, than, 'non-mammalian,', in, character])]). relacion([sujeto(['HZ']), verbo([mediates]), complemento([peroxidation, of, unsaturated, fatty, acids, and, production, of, bioactive, aldehydes, such, as, 4, -, hydroxynonenal, '(', 'HNE)'])]). relacion([sujeto(['HZ-laden', human, monocytes]), verbo([inhibited]), complemento([growth, of, cocultivated, human, erythroid, cells, and, produced, 'HNE', that, diffused, to, adjacent, cells, generating, 'HNE-protein', adducts])]). relacion([sujeto(['Cocultivation', with, 'HZ', or, treatment, with, low, micromolar, 'HNE']), verbo([inhibited]), complemento([growth, of, erythroid, cells, interfering, with, cell, cycle, without, apoptosis])]). relacion([sujeto(['After', 'HZ/HNE', 'treatment,', 2, critical, proteins, in, 'cell-cycle', 'regulation,', p53, and, 'p21,', were]), verbo([increased]), complemento([and, the, retinoblastoma, 'protein,', central, regulator, of, 'G₁-to-S-phase', 'transition,', was, consequently, 'hypophosphorylated,', while, 'GATA-1,', master, transcription, factor, in, erythropoiesis, was, reduced])]). relacion([sujeto(['The', resultant]), verbo([decreased]), complemento([expression, of, cyclin, 'A', and, 'D2', retarded, 'cell-cycle', progression, in, erythroid, cells, and, the, 'K562', cell, line])]). relacion([sujeto(['As', a, second, major, 'effect,', 'HZ', and, 'HNE']), verbo([inhibited]), complemento([protein, expression, of, crucial, receptors, '(', 'R):', 'transferrinR1,', stem, cell, 'factorR,', 'interleukin-3R,', and, erythropoietinR])]). relacion([sujeto(['The', reduced, receptor, expression, and, the, impaired, 'cell-cycle', activity]), verbo([decreased]), complemento([the, production, of, cells, expressing, 'glycophorin-A', and, hemoglobin])]). relacion([sujeto(['Present', data, confirm, the, inhibitory, role, of, 'HZ,', identify, 'HNE', as, one, 'HZ-generated', inhibitory, molecule, and, describe, molecular]), verbo([targets]), complemento([of, 'HNE', in, erythroid, progenitors, possibly, involved, in, erythropoiesis, inhibition, in, malaria, anemia])]). relacion([sujeto(['Oncogene-mediated', transformation, of, hematopoietic, cells]), verbo([has]), complemento([been, studied, 'extensively,', but, little, is, known, about, the, molecular, basis, for, restriction, of, oncogenes, to, certain, target, cells, and, differential, cellular, 'context-specific', requirements, for, oncogenic, transformation, between, infant, and, adult, leukemias])]). relacion([sujeto(['Understanding', cell, 'type-specific', interplay, of, signaling, pathways, and, oncogenes, is, essential, for, developing]), verbo([targeted]), complemento([cancer, therapies])]). relacion([sujeto(['Failure', of, a, direct, 'GATA1-E2F', interaction, in, mutated, 'GATA1s', converges, with, overactive, 'IGF', signaling, to]), verbo([promote]), complemento([cellular, transformation, of, 'DS', fetal, 'progenitors,', revealing, a, 'complex,', fetal, 'stage-specific', regulatory, network])]). relacion([sujeto(['Considerable', progress]), verbo([has]), complemento([been, made, in, elucidating, 'GATA', 'factor-dependent', genetic, networks, that, control, blood, cell, development])]). relacion([sujeto(['GATA-2', is]), verbo([required]), complemento([for, the, genesis, 'and/or', function, of, hematopoietic, stem, 'cells,', whereas, 'GATA-1', drives, the, differentiation, of, hematopoietic, progenitors, into, a, subset, of, the, blood, cell, lineages])]). relacion([sujeto(['GATA-1', directly, represses, 'Gata2', 'transcription,', and, this]), verbo([involves]), complemento(['GATA-1-mediated', displacement, of, 'GATA-2', from, 'chromatin,', a, process, termed, a, 'GATA', switch])]). relacion([sujeto(['Hemangioblasts,', which]), verbo([have]), complemento([a, differentiation, potential, for, both, endothelial, and, hematopoietic, 'lineages,', arise, in, the, primitive, streak, and, migrate, into, the, yolk, sac, to, form, blood, 'islands,', where, primitive, hematopoiesis, occurs])]). relacion([sujeto(['ZFAT', '(', a, 'zinc-finger', gene, in, autoimmune, thyroid, disease, susceptibility, 'region/an', 'immune-related', transcriptional, regulator, containing, 18, 'C(2)H(2)-type', 'zinc-finger', domains, and, one, 'AT-hook)', was, originally, identified, as, an, 'immune-related', transcriptional, regulator, containing, 18, 'C(2)H(2)-type', 'zinc-finger', domains, and, one, 'AT-hook,', and, is, highly]), verbo([conserved]), complemento([among, species])]). relacion([sujeto(['ZFAT', is, thought, to, be, a, critical, transcription, factor]), verbo([involved]), complemento([in, 'immune-regulation', and, 'apoptosis;', 'however,', developmental, roles, for, 'ZFAT', remain, unknown])]). relacion([sujeto(['Expression', levels, of, 'Tal1,', 'Lmo2,', and, 'Gata1', in, 'Zfat(-/-)', yolk, sacs, are, much, reduced, compared, with, those, of, 'wild-type', 'mice,', and, 'ChIP-PCR', analysis, revealed, that, 'ZFAT']), verbo([binds]), complemento([promoter, regions, for, these, genes, in, vivo])]). relacion([sujeto(['Taken', 'together,', these, results]), verbo([suggest]), complemento([that, 'ZFAT', is, indispensable, for, mouse, embryonic, development, and, functions, as, a, critical, transcription, factor, for, primitive, hematopoiesis, through, 'direct-regulation', of, 'Tal1,', 'Lmo2,', and, 'Gata1'])]). relacion([sujeto(['Elucidation', of, 'ZFAT', functions, in, hematopoiesis, might]), verbo([lead]), complemento([to, a, better, understanding, of, transcriptional, networks, in, differentiation, and, cellular, programs, of, hematopoietic, lineage, and, provide, useful, information, for, applied, medicine, in, stem, cell, therapy])]). relacion([sujeto(['Sulfatase', modifying, factor, 1, '(', 'SUMF1)']), verbo([activates]), complemento([the, 'Sulf1', and, 'Sulf2', sulfatases, that, remodel, the, 'HSPGs,', and, is, mutated, in, patients, with, multiple, sulfatase, deficiency])]). relacion([sujeto(['Here,', we, show, that, the, 'FGF', signaling, pathway, is, constitutively]), verbo([activated]), complemento([in, 'Sumf1(-/-)', 'HSCs', and, hematopoietic, stem, progenitor, cells, '(', 'HSPCs)'])]). relacion([sujeto(['These', cells, show]), verbo([increased]), complemento(['p-extracellular', 'signal-regulated', kinase, 'levels,', which, in, turn, promote, 'beta-catenin', accumulation])]). relacion([sujeto(['Transplantation', of, 'Sumf1(-/-)', 'HSPCs', into, 'wild-type', mice, reconstituted, the, phenotype, of, the, 'donors,']), verbo([suggesting]), complemento([a, cell, autonomous, defect])]). relacion([sujeto(['Despite', some, differences, in, molecular, 'organization,', teleost, 'G6F-like', and, tetrapod, 'G6F', seem, orthologous, as, they, map, to, similar, genomic, 'location,', share, typical, motifs, in, transmembrane, and, cytoplasmic, 'regions,', and, are, both]), verbo([expressed]), complemento([by, 'thrombocytes/platelets'])]). relacion([sujeto(['In', the, crucian, carps, goldfish, '(', 'Carassius', auratus, 'auratus)', and, ginbuna, '(', 'Carassius', auratus, 'langsdorfii),', 'G6F-like', was]), verbo([found]), complemento([expressed, not, only, by, thrombocytes, but, also, by, 'erythrocytes,', supporting, that, erythroid, and, thromboid, cells, in, teleost, fish, form, a, hematopoietic, lineage, like, they, do, in, mammals])]). relacion([sujeto(['The', 'ITAM-bearing', of, 'G6F-like']), verbo([suggests]), complemento([that, the, molecule, plays, an, important, role, in, cell, 'activation,', and, 'G6F-like', expression, by, erythrocytes, suggests, that, these, cells, have, functional, overlap, potential, with, thrombocytes])]). relacion([sujeto(['We', present, the, first, transcriptional, regulatory, element]), verbo([found]), complemento([in, a, 'PAH', gene, intron])]). relacion([sujeto(['The', element, is, located, in, the, 'PAH', gene, intron, 8, ',']), verbo([acts]), complemento([as, an, enhancer, specifically, in, the, hepatoma, cell, 'line,', and, binds, 'GATA-1', transcription, factor])]). relacion([sujeto(['FOG1,', a, 'GATA1-interaction', 'partner,', is, critical, for, 'GATA1', function, in, several, contexts, by, bringing, multiple, complexes, into, association, with, 'GATA1', to, facilitate, activation, or, repression, of]), verbo([target]), complemento([genes])]). relacion([sujeto(['We']), verbo([found]), complemento([that, 'FOG1', is, 'SUMOylated', and, phosphorylated, in, erythroid, cells, in, a, 'differentiation-dependent', manner])]). relacion([sujeto(['Removal', of, the, 'SUMOylation', sites, in, 'FOG1', does, not, impair]), verbo([nuclear]), complemento(['localization,', protein, 'stability,', or, chromatin, occupancy])]). relacion([sujeto(['However,', 'SUMOylation', of, 'FOG1']), verbo([modulates]), complemento([interactions, with, 'C-terminal', binding, protein, family, 'members,', specifically, promoting, 'CTBP1', binding])]). relacion([sujeto(['Phosphorylation', of, 'FOG1']), verbo([modulates]), complemento(['SUMOylation', 'and,', 'therefore,', indirectly, regulates, the, 'CTBP', interaction])]). relacion([sujeto(['Post-translational', modification, of, 'FOG1', may, contribute, to, control, of, 'co-occupancy', by, 'CTBP', family, 'members,', the, 'NuRD', 'complex,', and, 'GATA1', at, differentially]), verbo([regulated]), complemento([genes])]). relacion([sujeto(['Here,', we]), verbo([have]), complemento([evaluated, whether, anagrelide, interferes, with, the, major, signal, transduction, cascades, stimulated, by, thrombopoietin, in, the, hematopoietic, cell, line, 'UT-7/mpl', and, in, cultured, 'CD34(+)', -, derived, human, hematopoietic, cells])]). relacion([sujeto(['In', 'addition,', we]), verbo([have]), complemento([used, quantitative, mRNA, expression, analysis, to, assess, whether, the, drug, affects, the, levels, of, known, transcription, factors, that, control, megakaryocytopoiesis])]). relacion([sujeto(['Anagrelide']), verbo([suppresses]), complemento([megakaryocytopoiesis, by, reducing, the, expression, levels, of, 'GATA-1', and, 'FOG-1', via, a, 'PDEIII-independent', mechanism, that, is, differentiation, 'context-specific', and, does, not, involve, inhibition, of, 'MPL-mediated', early, signal, transduction, events])]). relacion([sujeto(['Ldb1', and, erythroid, partners, 'SCL,', 'GATA-1,', and, 'LMO2', form, a, complex, that, is]), verbo([required]), complemento([to, establish, spatial, proximity, between, the, 'β-globin', locus, control, region, and, gene, and, for, transcription, activation, during, erythroid, differentiation])]). relacion([sujeto(['In', 'addition,', 'Ldb1', is, necessary, for, enrichment, of, key, transcriptional, components, in, the, 'locus,', including, 'P-TEFb,', which]), verbo([phosphorylates]), complemento(['Ser2', of, the, 'RNA', polymerase, 'C-terminal', domain, for, efficient, elongation])]). relacion([sujeto(['Furthermore,', reduction, of, 'Ldb1', results, in, the, inability, of, the, locus, to, migrate, away, from, the]), verbo([nuclear]), complemento(['periphery,', which, is, necessary, to, achieve, robust, transcription, of, 'β-globin', in, nuclear, transcription, factories])]). relacion([sujeto(['These', results, implicate, 'Ldb1', as, a, factor, that, facilitates]), verbo([nuclear]), complemento([relocation, for, transcription, activation])]). relacion([sujeto(['The', basic, 'helix-loop-helix', hemopoietic, transcriptional, regulator, 'TAL1', '(', formerly, 'SCL)', is]), verbo([required]), complemento([for, terminal, differentiation, of, red, blood, cells])]). relacion([sujeto(['To']), verbo([gain]), complemento([insight, into, 'TAL1', function, and, mechanisms, of, action, in, 'erythropoiesis,', we, performed, 'ChIP-sequencing', and, gene, expression, analyses, from, primary, fetal, liver, erythroid, cells])]). relacion([sujeto(['The', majority, of, 'TAL1\'s', genomic]), verbo([targets]), complemento([require, direct, 'DNA-binding', activity])]). relacion([sujeto(['However,', 'one-fifth', of, 'TAL1\'s']), verbo([target]), complemento(['sequences,', mainly, among, those, showing, high, affinity, for, 'TAL1,', can, recruit, the, factor, independently, of, its, 'DNA', binding, activity])]). relacion([sujeto(['An', unbiased, 'DNA', motif, search, of, sequences]), verbo([bound]), complemento([by, 'TAL1', identified, 'CAGNTG', as, 'TAL1-preferred', 'E-box', motif, in, erythroid, cells])]). relacion([sujeto(['Novel', motifs, were, also, characterized, that, may, help, distinguish]), verbo([activated]), complemento([from, repressed, genes, and, suggest, a, new, mechanism, by, which, 'TAL1', may, be, recruited, to, 'DNA'])]). relacion([sujeto(['Finally,', analysis, of, recruitment, of, 'GATA1,', a, protein, partner, of, 'TAL1,', to, sequences, occupied, by, 'TAL1']), verbo([suggests]), complemento([that, 'TAL1\'s', binding, is, necessary, prior, or, simultaneous, to, that, of, 'GATA1'])]). relacion([sujeto(['This', work]), verbo([provides]), complemento([the, framework, to, study, regulatory, networks, leading, to, erythroid, terminal, maturation, and, to, model, mechanisms, of, action, of, 'tissue-specific', transcription, factors])]). relacion([sujeto(['Erythroid', 'differentiation-associated', gene, '(', 'EDAG),', a, hematopoietic, 'tissue-specific', transcription, 'regulator,', plays, a, key, role, in]), verbo([maintaining]), complemento([the, homeostasis, of, hematopoietic, lineage, commitment])]). relacion([sujeto(['However,', the, mechanism, and, genes]), verbo([regulated]), complemento([by, 'EDAG', remain, unknown])]). relacion([sujeto(['In', this, 'study,', we, showed, that, overexpression, of, 'EDAG', in, a, myeloid, cell, line, 32, 'D']), verbo([led]), complemento([to, an, erythroid, phenotype, with, increased, number, of, 'benzidine-positive', cells, and, 'up-regulation', of, erythroid, specific, surface, marker, 'TER119'])]). relacion([sujeto(['The', megakaryocytic, specific, marker, 'CD61', was, also]), verbo([induced]), complemento([significantly])]). relacion([sujeto(['Using', a, 'genome-wide', microarray, analysis, and, a, twofold, change, 'cutoff,', we, identified, 332, genes, with, reduced, expression, and, 288, genes, with]), verbo([increased]), complemento([expression])]). relacion([sujeto(['Among', 'up-regulation', 'genes,', transcription, factor, 'GATA-1', and, its]), verbo([target]), complemento([genes, including, 'EKLF,', 'NF-E2,', 'Gfi-1b,', 'hemogen,', 'SCL,', hemoglobin, 'alpha,', beta, and, megakaryocytic, gene, 'GPIX', were, increased])]). relacion([sujeto(['Taken', 'together,', 'EDAG', functions, as, a, positive, regulator, of, 'erythroid/megakaryocytic', differentiation, in, 32, 'D', cells]), verbo([associated]), complemento([with, the, induction, of, 'GATA-1', and, its, target, genes])]). relacion([sujeto(['To', determine, the, role, of, vascular, endothelial, growth, factor, '(', 'Vegf)', in, embryonic, erythroid, development, we]), verbo([have]), complemento([deleted, or, overexpressed, 'Vegf', specifically, in, the, erythroid, lineage, using, the, 'EpoR-iCre', transgenic, line, in, combination, with, 'Cre/loxP', conditional, gain, and, loss, of, function, 'Vegf', alleles])]). relacion([sujeto(['Conditional', deletion, of, 'Vegf', within, the, erythroid, lineage, was]), verbo([associated]), complemento([with, increased, 'Gata1', levels, and, increased, erythroid, differentiation])]). relacion([sujeto(['Expression', of, a, 'ROSA26-based', 'GATA2', transgene, rescued, 'Gata1', mRNA, levels, and]), verbo([target]), complemento([genes, and, restored, erythroid, differentiation, in, our, 'Vegf', gain, of, function, model])]). relacion([sujeto(['These', results, demonstrate, that, 'Vegf']), verbo([modulates]), complemento(['Gata1', expression, levels, in, vivo, and, provides, new, molecular, insight, into, 'Vegf\'s', ability, to, modulate, erythropoiesis])]). relacion([sujeto(['Reduced', levels, of, 'BCL11A']), verbo([have]), complemento([been, shown, to, delay, switching, from, fetal, to, adult, 'hemoglobin,', suggesting, that, it, acts, as, a, 'stage-specific', repressor, of, gamma, globin, expression])]). relacion([sujeto(['We']), verbo([have]), complemento([carried, out, a, survey, of, 'BCL11A', binding, in, the, 'globin,', 'BCL11A', and, 'GATA1', loci, by, 'ChIP-on-chip', analysis, in, primary, human, erythroid, cells])]). relacion([sujeto(['We']), verbo([found]), complemento([strong, occupancy, in, both, alpha, and, beta, globin, upstream, regulatory, regions, as, well, as, in, regions, involved, in, switching, and, hereditary, persistence, of, fetal, hemoglobin])]). relacion([sujeto(['Genetic', studies]), verbo([have]), complemento([identified, a, restricted, 14, kb, region, in, 'BCL11A', intron, 2, as, being, highly, associated, with, 'HbF', levels])]). relacion([sujeto(['Strong', 'GATA-1']), verbo([binding]), complemento([and, acetylated, histone, 'H3', was, found, in, this, 'area,', which, could, be, indicative, of, a, regulatory, 'element,', changes, in, which, might, be, responsible, for, the, overall, regulation, of, 'BCL11A'])]). relacion([sujeto(['We', also, observed, 'BCL11A', and, 'GATA-1']), verbo([binding]), complemento([in, a, known, 'auto-regulatory', promoter, element, of, the, 'GATA1', locus])]). relacion([sujeto(['Helper', 'T', '(', 'Th)', cells, are, deeply]), verbo([involved]), complemento([in, the, pathophysiology, of, bronchial, 'asthma,', such, as, eosinophilic, 'inflammation,', bronchial, hyperresponsiveness, '(', 'BHR),', airflow, limitation, and, remodeling])]). relacion([sujeto(['The', number, of, 'BALF', eosinophils, was, significantly]), verbo([increased]), complemento([in, 'WT', 'mice,', but, not, detectable, in, 'Delta', dblGATA, mice])]). relacion([sujeto(['BHR', was, also]), verbo([induced]), complemento([in, 'WT', 'mice,', but, significantly, attenuated, in, 'Delta', dblGATA, mice])]). relacion([sujeto(['Eosinophils', are]), verbo([involved]), complemento([in, 'T-cell-mediated', 'BHR'])]). relacion([sujeto(['KLF1']), verbo([regulates]), complemento([a, diverse, suite, of, genes, to, direct, erythroid, cell, differentiation, from, bipotent, progenitors])]). relacion([sujeto(['We']), verbo([found]), complemento([at, least, 945, sites, in, the, genome, of, 'E14'])]). relacion([sujeto(['Our', data]), verbo([suggests]), complemento(['KLF1', directly, regulates, most, aspects, of, terminal, erythroid, differentiation, including, production, of, 'alpha-', and, 'beta-globin', protein, 'chains,', heme, 'biosynthesis,', coordination, of, proliferation, and, 'anti-apoptotic', 'pathways,', and, construction, of, the, red, cell, membrane, and, cytoskeleton, by, functioning, primarily, as, a, transcriptional, activator])]). relacion([sujeto(['Additionally,', we]), verbo([suggest]), complemento([new, mechanisms, for, 'KLF1', cooperation, with, other, transcription, 'factors,', in, particular, the, erythroid, transcription, factor, 'GATA1,', to, maintain, homeostasis, in, the, erythroid, compartment])]). relacion([sujeto(['Previously,', we]), verbo([found]), complemento([that, the, 'oxygen-binding', protein, hemoglobin, is, expressed, in, alveolar, 'Type', 'II', cells, '(', 'ATII)'])]). relacion([sujeto(['Here,', we]), verbo([report]), complemento([that, 'ATII', cells, also, express, a, number, of, highly, specific, transcription, factors, and, other, genes, normally, associated, with, hemoglobin, biosynthesis, in, erythroid, precursors])]). relacion([sujeto(['Because', 'hypoxia-inducible', factors, '(', 'HIFs)', were, shown, to, play, a, role, in, 'hypoxia-induced', changes, in, 'ATII', 'homeostasis,', we, hypothesized, that, the, 'hypoxia-induced']), verbo([increase]), complemento([in, intracellular, 'HIF', exerts, a, concomitant, effect, on, 'ATII', hemoglobin, expression])]). relacion([sujeto(['Treatment', of, cells, from, the, 'ATII-like', immortalized, mouse, lung, epithelial, cell, 'line-15', '(', 'MLE-15)', with, hypoxia, for, 20, hours, resulted, in, dramatic]), verbo([increases]), complemento([in, cellular, levels, of, 'HIF-2α', protein, and, parallel, significant, increases, in, hemoglobin, messenger, 'RNA', '(', 'mRNA)', and, protein, 'expression,', as, compared, with, that, of, control, cells, cultured, in, normoxia])]). relacion([sujeto(['Significant']), verbo([increases]), complemento([in, the, mRNA, of, 'globin-associated', transcription, factors, were, also, 'observed,', and, 'RNA', interference, '(', 'RNAi)', experiments, demonstrated, that, the, expression, of, hemoglobin, is, at, least, partially, dependent, on, the, cellular, levels, of, 'globin-associated', transcription, factor, isoform, 1, '(', 'GATA-1)'])]). relacion([sujeto(['Conversely,', levels, of, prosurfactant, proteins, 'B', and, 'C', significantly]), verbo([decreased]), complemento([in, the, same, cells, after, exposure, to, hypoxia])]). relacion([sujeto(['The', treatment, of, 'MLE-15', cells, cultured, in, normoxia, with, prolyl, 4, -, hydroxylase, 'inhibitors,', which, mimic, the, effects, of, 'hypoxia,', resulted, in]), verbo([increases]), complemento([of, hemoglobin, and, decreases, of, surfactant, proteins])]). relacion([sujeto(['Taken', 'together,', these, results]), verbo([suggest]), complemento([a, relationship, between, 'hypoxia,', 'HIFs,', and, the, expression, of, 'hemoglobin,', and, imply, that, hemoglobin, may, be, involved, in, the, 'oxygen-sensing', pathway, in, alveolar, epithelial, cells])]). relacion([sujeto(['Its', role, in]), verbo([regulating]), complemento(['erythroid-specific', genes, has, been, extensively, 'studied,', whereas, its, role, in, controlling, genes, that, regulate, cell, proliferation, is, less, understood])]). relacion([sujeto(['Ectopic', expression, of, 'GATA-1', in, erythroleukemia, cells]), verbo([releases]), complemento([the, block, to, their, differentiation, and, leads, to, terminal, cell, division])]). relacion([sujeto(['Remarkably,', ectopic, expression, of, p21, also]), verbo([induces]), complemento([the, erythroleukemia, cells, to, differentiate])]). relacion([sujeto(['We', now]), verbo([report]), complemento([that, 'GATA-1', directly, regulates, transcription, of, the, p21, gene, in, both, erythroleukemia, cells, and, normal, erythroid, progenitors])]). relacion([sujeto(['Using', 'reporter,', electrophoretic, mobility, 'shift,', and, chromatin, immunoprecipitation, 'assays,', we, show, that, 'GATA-1']), verbo([stimulates]), complemento([p21, gene, transcription, by, binding, to, consensus, binding, sites, in, the, upstream, region, of, the, p21, gene, promoter])]). relacion([sujeto(['This', activity, is, also, dependent, on, a]), verbo([binding]), complemento([site, for, 'Sp1/KLF-like', factors, near, the, transcription, start, site])]). relacion([sujeto(['Our', findings, indicate, that, p21, is, a, crucial, downstream, gene]), verbo([target]), complemento([and, effector, of, 'GATA-1', during, red, blood, cell, terminal, differentiation])]). relacion([sujeto(['The', 'Eight-Twenty-One', '(', 'ETO)']), verbo([nuclear]), complemento(['co-repressor', gene, belongs, to, the, 'ETO', homologue, family, also, containing, 'Myeloid', 'Translocation', 'Gene', on, chromosome, 16, '(', 'MTG16)', and, myeloid, translocation, 'Gene-Related', protein, 1, '(', 'MTGR1)'])]). relacion([sujeto(['Normal', functions, of, 'ETO', homologues]), verbo([have]), complemento([as, yet, not, been, examined])]). relacion([sujeto(['Strong', 'ETO', promoter, activity, was, specifically, observed, upon, transfection, of, a, promoter, reporter, construct, into, 'erythroid/megakaryocytic', 'cells,', which]), verbo([have]), complemento([endogeneous, 'ETO', gene, activity])]). relacion([sujeto(['An', evolutionary]), verbo([conserved]), complemento([region, of, 228, bp, revealed, potential, 'cis-elements', involved, in, transcription, of, 'ETO'])]). relacion([sujeto(['Disruption', of, the, evolutionary]), verbo([conserved]), complemento(['GATA', -, 636, consensus, binding, site, repressed, transactivation, and, disruption, of, the, 'ETS1', -, 705, consensus, binding, site, enhanced, activity, of, the, 'ETO', promoter])]). relacion([sujeto(['The', promoter, was]), verbo([stimulated]), complemento([by, overexpression, of, 'GATA-1', into, 'erythroid/megakaryocytic', cells])]). relacion([sujeto(['Electrophoretic', mobility, shift, assay, with, 'erythroid/megakaryocytic', cells, showed, specific]), verbo([binding]), complemento([of, 'GATA-1', to, the, 'GATA', -, 636, site])]). relacion([sujeto(['Furthermore,', results, from, chromatin, immunoprecipitation, showed, 'GATA-1']), verbo([binding]), complemento([in, vivo, to, the, conserved, region, of, the, 'ETO', promoter, containing, the, -, 636, site])]). relacion([sujeto(['The', results]), verbo([suggest]), complemento([that, the, 'GATA', -, 636, site, may, have, a, role, in, activation, of, the, 'ETO', gene, activity, in, cells, with, 'erythroid/megakaryocytic', potential])]). relacion([sujeto(['Leukemia']), verbo([associated]), complemento(['AML1-ETO', strongly, suppressed, an, 'ETO', promoter, reporter, in, 'erythroid/megakaryocytic', cells])]). relacion([sujeto(['We', demonstrate, that, the, 'GATA-1', transcription, factor]), verbo([binds]), complemento([and, transactivates, the, 'ETO', proximal, promoter, in, an, 'erythroid/megakaryocytic-specific', manner])]). relacion([sujeto(['The', dynamic, properties, of, these, elements, determine, the, functionality, of, genetic, networks]), verbo([regulating]), complemento([differentiation, and, development])]). relacion([sujeto(['We', also, show, that, the, triad]), verbo([acts]), complemento([as, a, 'low-pass', filter, by, switching, between, steady, states, only, in, response, to, signals, that, persist, for, longer, than, a, minimum, duration, threshold])]). relacion([sujeto(['We']), verbo([have]), complemento([found, that, the, 'auto-regulation', loops, connecting, the, 'slow-degrading', 'Scl', to, 'Gata2', and, 'Fli1', are, crucial, for, this, 'low-pass', filtering, property])]). relacion([sujeto(['Taken', together, our, analysis, not, only]), verbo([reveals]), complemento([new, insights, into, hematopoietic, stem, cell, regulatory, network, functionality, but, also, provides, a, novel, and, widely, applicable, strategy, to, incorporate, experimental, measurements, into, dynamical, network, models])]). relacion([sujeto(['The', discovery, of, 'JAK2', mutations, in, 'Philadelphia-negative', myeloproliferative, neoplasms]), verbo([has]), complemento([prompted, investigators, to, evaluate, 'mutation-targeted', treatments, to, restore, hematopoietic, cell, functions, in, these, diseases])]). relacion([sujeto(['However,', the, results, of, the, first, clinical, trials, with, 'JAK2', inhibitors, are, not, as, promising, as, 'expected,', prompting, a, search, for, additional, drugable]), verbo([targets]), complemento([to, treat, these, disorders])]). relacion([sujeto(['In', this, 'paper,', we, used, the, hypomorphic, 'Gata1(low)', mouse, model, of, primary, myelofibrosis, '(', 'PMF),', the, most, severe, of, these, 'neoplasms,', to, test, the, hypothesis, that, defective, marrow, hemopoiesis, and, development, of, extramedullary, hematopoiesis, in, myelofibrosis, is, due, to, insufficient, 'p27(Kip1)', activity, and, is, treatable, by, 'Aplidin,', a, cyclic, depsipeptide, that]), verbo([activates]), complemento(['p27(Kip1)', in, several, cancer, cells])]). relacion([sujeto(['Aplidin', restored, expression, of, 'Gata1', and, 'p27(Kip1)', in, 'Gata1(low)', hematopoietic, 'cells,', proliferation, of, marrow, progenitor, cells, in, vitro, and, maturation, of, megakaryocytes, in, vivo, '(', reducing, 'TGF-beta/VEGF', levels]), verbo([released]), complemento([in, the, microenvironment, by, immature, 'Gata1(low)', 'megakaryocytes)'])]). relacion([sujeto(['These', results, indicate, that, 'Aplidin', effectively, alters, the, natural, history, of, myelofibrosis, in, 'Gata1(low)', mice, and]), verbo([suggest]), complemento([this, drug, as, candidate, for, clinical, evaluation, in, 'PMF'])]). relacion([sujeto(['Small', 'ubiquitin-like', modifier, '(', 'SUMO)', modification, of, proteins, '(', 'SUMOylation)', and, deSUMOylation]), verbo([have]), complemento([emerged, as, important, regulatory, mechanisms, for, protein, function])]). relacion([sujeto(['We']), verbo([have]), complemento([created, 'SENP1', knockout, '(', 'KO)', mice, based, on, a, 'Cre-loxP', system])]). relacion([sujeto(['Global', deletion, of, 'SENP1', '(', 'SENP1', 'KO)']), verbo([causes]), complemento([anemia, and, embryonic, lethality, between, embryonic, day, 13.5, and, postnatal, day, 1, ',', correlating, with, erythropoiesis, defects, in, the, fetal, liver])]). relacion([sujeto(['Bone', marrow, transplantation, of, 'SENP1', 'KO', fetal, liver, cells, to, irradiated, adult, recipients]), verbo([confers]), complemento([erythropoiesis, defects])]). relacion([sujeto(['We', further, show, that, 'SENP1', can, directly, deSUMOylate, 'GATA1,']), verbo([regulating]), complemento(['GATA1-dependent', gene, expression, and, erythropoiesis, by, in, vitro, assays])]). relacion([sujeto(['Collectively,', we, conclude, that, 'SENP1']), verbo([promotes]), complemento(['GATA1', activation, and, subsequent, erythropoiesis, by, deSUMOylating, 'GATA1'])]). relacion([sujeto(['By']), verbo([expressing]), complemento(['EVI1', in, murine, bone, marrow, '(', 'BM),', we, previously, described, a, myelodysplastic, syndrome, '(', 'MDS)', model, characterized, by, 'pancytopenia,', 'dysmegakaryopoiesis,', 'dyserythropoiesis,', and, 'BM', failure])]). relacion([sujeto(['Here,', we, show, that, a, double, point, mutant, 'EVI1-(1+6Mut),', unable, to]), verbo([bind]), complemento(['Gata1,', abrogates, the, onset, of, 'MDS', in, the, mouse, and, 're-establishes', normal, 'megakaryopoiesis,', 'erythropoiesis,', 'BM', 'function,', and, peripheral, blood, profiles])]). relacion([sujeto(['These', normal, features, were]), verbo([maintained]), complemento([in, the, reconstituted, mice, until, the, study, was, ended, at, 21, months, after, 'BMT'])]). relacion([sujeto(['We', also]), verbo([report]), complemento([that, 'EVI1', deregulates, several, genes, that, control, cell, division, and, cell, 'self-renewal'])]). relacion([sujeto(['In', 'particular,', the, silencing, of, 'miRNA-124', by, 'DNA', methylation, is]), verbo([associated]), complemento([with, 'EVI1', 'expression,', but, not, that, of, the, 'EVI1', 'mutant,', and, appears, to, play, a, key, role, in, the, 'up-regulation', of, cell, division, in, murine, 'BM', cells, and, in, the, hematopoietic, cell, line, 32, 'Dcl3'])]). relacion([sujeto(['The', results, presented, here, demonstrate, that, 'EVI1']), verbo([induces]), complemento(['MDS', in, the, mouse, through, two, major, 'pathways,', both, of, which, require, the, interaction, of, 'EVI1', with, other, 'factors:', 'one,', results, from, 'EVI1-Gata1', 'interaction,', which, deregulates, erythropoiesis, and, leads, to, fatal, 'anemia,', whereas, the, other, occurs, by, interaction, of, 'EVI1', with, unidentified, factors, causing, perturbation, of, the, cell, cycle, and, 'self-renewal,', as, a, consequence, of, silencing, 'miRNA-124', by, 'EVI1', 'and,', 'ultimately,', ensues, in, 'BM', failure])]). relacion([sujeto(['The', human, 'beta-globin', genes, are]), verbo([expressed]), complemento([in, a, developmentally, controlled, fashion])]). relacion([sujeto(['Studies', on, the, molecular, mechanisms, underlying, the, 'stage-specific', regulation, of, globin, genes]), verbo([have]), complemento([been, fueled, by, the, clinical, benefit, of, elevated, fetal, 'gamma-globin', expression, in, patients, with, sickle, cell, anemia, and, thalassemia])]). relacion([sujeto(['Recent']), verbo([reports]), complemento([suggested, a, role, of, the, hematopoietic, transcription, factor, 'GATA-1,', its, cofactor, 'FOG-1,', and, the, associated, chromatin, remodeling, complex, 'NuRD', in, the, developmental, silencing, of, 'HBG1', and, 'HBG2', gene, expression])]). relacion([sujeto(['We']), verbo([found]), complemento([that, the, 'FOG-1/NuRD', interaction, is, dispensable, for, the, silencing, of, human, 'HBG1', and, 'HBG2', expression])]). relacion([sujeto(['In', 'contrast,', a, significant, reduction, of, 'adult-type', human, and, murine, globin, gene, expression, was]), verbo([found]), complemento([in, adult, bone, marrows, of, mutant, animals])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento(['that,', 'unexpectedly,', 'NuRD', is, required, for, 'FOG-1-dependent', activation, of, 'adult-type', globin, gene, expression, but, is, dispensable, for, human, 'gamma-globin', silencing, in, vivo])]). relacion([sujeto(['A', high, incidence, of, chromosomal, 'abnormalities,', in, particular, trisomy, 21, ',']), verbo([has]), complemento([been, described, in, fetuses, with, pericardial, effusion])]). relacion([sujeto(['To', our, 'knowledge,', only, one, such, case]), verbo([has]), complemento([been, reported, to, date])]). relacion([sujeto(['The', mechanism, that, sorts, the, 'alpha-granule', components, into, distinct, structures, and]), verbo([mediates]), complemento([their, release, in, response, to, specific, stimuli, is, now, emerging])]). relacion([sujeto(['P-selectin', and, von, 'Willebrand', factor, are, two, proteins, present, in, the, 'alpha-granules', that]), verbo([recognize]), complemento(['P-selectin', glycoprotein, ligand, on, neutrophils, and, collagen, in, the, subendothelial, matrix])]). relacion([sujeto(['These', proteins, may, play, an, important, role, in, determining, the, differential]), verbo([release]), complemento([of, the, 'alpha-granule', contents, in, response, to, external, stimuli])]). relacion([sujeto(['To', clarify, this, 'question,', we, analyzed, by, immunoelectron, microscopy, the, localization, of, von, 'Willebrand', factor, and, 'P-selectin', during, the, maturation, of, 'wild-type', and, 'Gata1(low)', megakaryocytes]), verbo([induced]), complemento([in, vivo, by, treating, animals, with, thrombopoietin])]). relacion([sujeto(['The', maturation, block]), verbo([induced]), complemento([by, this, mutation, is, partially, rescued, by, treatment, in, vivo, with, thrombopoietin])]). relacion([sujeto(['These', observations, support, the, hypothesis, that, 'P-selectin', and, von, 'Willebrand', factor, may]), verbo([ensure]), complemento([differential, release, of, the, 'alpha-granule', content, in, response, to, external, stimuli])]). relacion([sujeto(['Hematopoietic', development, during, embryogenesis]), verbo([involves]), complemento([the, interaction, of, extrinsic, signaling, pathways, coupled, to, an, intrinsic, cell, fate, that, is, regulated, by, 'cell-specific', transcription, factors])]). relacion([sujeto(['Retinoic', acid, '(', 'RA)']), verbo([has]), complemento([been, linked, to, stem, cell, 'self-renewal', in, adults, and, also, participates, in, yolk, sac, blood, island, formation])]). relacion([sujeto(['Here,', we, demonstrate, that, 'RA']), verbo([decreases]), complemento([gata1, expression, and, blocks, primitive, hematopoiesis, in, zebrafish, '(', 'Danio', 'rerio)', 'embryos,', while, increasing, expression, of, the, vascular, 'marker,', fli1])]). relacion([sujeto(['Treatment', with, an, inhibitor, of, 'RA', biosynthesis, or, a, retinoic, acid, receptor, antagonist]), verbo([increases]), complemento(['gata1(+)', erythroid, progenitors, in, the, posterior, mesoderm, of, 'wild-type', embryos, and, anemic, 'cdx4(-/-)', 'mutants,', indicating, a, link, between, the, 'cdx-hox', signaling, pathway, and, 'RA'])]). relacion([sujeto(['Overexpression', of, 'scl,', a, 'DNA']), verbo([binding]), complemento([protein, necessary, for, hematopoietic, 'development,', rescues, the, block, of, hematopoiesis, induced, by, 'RA'])]). relacion([sujeto(['We', show, that, these, effects, of, 'RA', and, 'RA', pathway, inhibitors, are]), verbo([conserved]), complemento([during, primitive, hematopoiesis, in, murine, yolk, sac, explant, cultures, and, embryonic, stem, cell, assays])]). relacion([sujeto(['Taken', 'together,', these, data, indicate, that, 'RA']), verbo([inhibits]), complemento([the, commitment, of, mesodermal, cells, to, hematopoietic, 'fates,', functioning, downstream, of, cdx4, and, upstream, of, scl])]). relacion([sujeto(['Our', studies, establish, a, new, connection, between, 'RA', and, scl, during, development, that, may]), verbo([participate]), complemento([in, stem, cell, 'self-renewal', and, hematopoietic, differentiation])]). relacion([sujeto(['Heat', shock, protein, 27, '(', 'HSP27)', is, a, chaperone, whose, cellular, expression]), verbo([increases]), complemento([in, response, to, various, stresses, and, protects, the, cell, either, by, inhibiting, apoptotic, cell, death, or, by, promoting, the, ubiquitination, and, proteasomal, degradation, of, specific, proteins])]). relacion([sujeto(['In', 2, models, of, erythroid, 'differentiation;', that, 'is,', in, the, human, erythroleukemia, cell, 'line,', 'K562']), verbo([induced]), complemento([to, differentiate, into, erythroid, cells, on, hemin, exposure, and, 'CD34(+)', human, cells, ex, vivo, driven, to, erythroid, differentiation, in, liquid, 'culture,', depletion, of, 'HSP27', provokes, an, accumulation, of, 'GATA-1', and, impairs, terminal, maturation])]). relacion([sujeto(['More', 'specifically,', we, demonstrate, 'that,', in, the, late, stages, of, the, erythroid, differentiation, 'program,', 'HSP27', is]), verbo([phosphorylated]), complemento([in, a, 'p38-dependent', 'manner,', enters, the, 'nucleus,', binds, to, 'GATA-1,', and, induces, its, ubiquitination, and, proteasomal, 'degradation,', provided, that, the, transcription, factor, is, acetylated])]). relacion([sujeto(['To', evaluate, the, effects, of, the, transcription, factor, 'GATA-1', on, determining, cell, fate, between, dendritic, cell, '(', 'DC)', and, mast, cell, '(', 'MC)', 'lineages,', 'GATA-1', was, exogenously]), verbo([expressed]), complemento([in, bone, 'marrow-derived', '(', 'BM)', 'DCs'])]). relacion([sujeto(['Exogenous', expression, of, 'GATA-1', by, a, retrovirus, in, 'BMDCs']), verbo([inhibited]), complemento([expression, of, 'CD11c,', 'CD80,', 'CD86,', and, major, histocompatibility, complex, class, 'II', with, suppression, of, 'antigen-presenting', ability, and, morphological, changes, toward, 'granulocyte-like', cells])]). relacion([sujeto(['These', results, indicate, that, 'GATA-1']), verbo([suppresses]), complemento(['PU'])]). relacion([sujeto(['Thus,', 'GATA-1', appears, to, determine, cell, fate, by]), verbo([regulating]), complemento([several, 'cell-specific', transcription, factors])]). relacion([sujeto(['BCL11A']), verbo([binds]), complemento([the, upstream, locus, control, region, '(', 'LCR),', 'epsilon-globin,', and, the, intergenic, regions, between, 'gamma-globin', and, 'delta-globin', genes])]). relacion([sujeto(['A', chromosome, conformation, capture, '(', 3, 'C)', assay, shows, that, 'BCL11A', reconfigures, the, 'beta-globin', cluster, by]), verbo([modulating]), complemento([chromosomal, loop, formation])]). relacion([sujeto(['We', also, show, that, 'BCL11A', and, the, 'HMG-box-containing', transcription, factor, 'SOX6']), verbo([interact]), complemento([physically, and, functionally, during, erythroid, maturation])]). relacion([sujeto(['These', findings, collectively, demonstrate, that, transcriptional, silencing, of, 'gamma-globin', genes, by, 'BCL11A']), verbo([involves]), complemento(['long-range', interactions, and, cooperation, with, 'SOX6'])]). relacion([sujeto(['Our', findings]), verbo([provide]), complemento([insight, into, the, mechanism, of, 'BCL11A', action, and, new, clues, for, the, developmental, gene, regulatory, programs, that, function, at, the, 'beta-globin', locus])]). relacion([sujeto(['In', 'total,', 42, differentially]), verbo([expressed]), complemento([proteins, from, the, progeny, of, irradiated, cells, were, 'screened,', of, which, 17, were, identified, by, matrix, assistant, laser, desorption, 'ion-top', 'flight-mass', spectrometry, '(', 'MALDI-TOF-MS)', analysis])]). relacion([sujeto(['Database', search, revealed, that, these, differentially]), verbo([expressed]), complemento([proteins, may, function, in, cell, cycle, 'regulation,', cytoskeleton, 'maintenance,', stress, 'response,', and, tumor, 'metastasis,', indicating, an, effect, of, 'radiation-induced', genomic, instability, '(', 'RIGI)', in, the, progeny, of, irradiated, cells])]). relacion([sujeto(['Analysis', on, functional, roles, of, the, screened, proteins, may]), verbo([provide]), complemento([insight, into, further, mechanistic, investigations, underlying, molecular, events, induced, by, 'RIGI'])]). relacion([sujeto(['Although', the, anticancer, activities, of, histone, deacetylase, '(', 'HDAC)', inhibitors]), verbo([have]), complemento([been, 'studied,', a, role, for, 'HDAC', in, normal, hematopoiesis, has, not, been, clearly, defined])]). relacion([sujeto(['Previous', studies]), verbo([have]), complemento([shown, that, the, potent, 'HDAC', inhibitor, 'FK228', stimulates, interleukin, '(', 'IL)-3-mediated', erythropoiesis])]). relacion([sujeto(['In', the, 'serum-free', cultures, containing, 'IL-3+stem', cell, factor, '(', 'SCF),', 'VPA', significantly]), verbo([increased]), complemento([generation, of, 'CD61(+)GPA(-)', megakaryocytic, and, a, 'CD61(+)GPA(+)', mixture, of, megakaryocytic, and, erythroid, precursors, from, 'CD34(+)', hematopoietic, precursors, at, a, pharmacological, concentration, '(', 100, 'microg/mL)'])]). relacion([sujeto(['The']), verbo([increase]), complemento([in, generation, of, megakaryocytic, and, erythroid, precursors, by, 'VPA', was, confirmed, by, replating, cultured, cells, with, 'thrombopoietin+SCF', and, 'erythropoietin+SCF,', respectively])]). relacion([sujeto(['In', cultures, with, 'granulocyte-macrophage', 'colony-stimulating', 'factor+SCF,', where, 'CD61(-)GPA(+)', erythroid, precursors, were, mostly, 'developed,', 'VPA', mainly]), verbo([enhanced]), complemento([the, generation, of, 'CD61(-)GPA(+)', erythroid, precursors])]). relacion([sujeto(['Furthermore,', these]), verbo([stimulating]), complemento([effects, of, 'VPA', were, observed, by, incubating, 'CD34(+)', cells, from, patients, with, myelodysplastic, syndrome])]). relacion([sujeto(['Quantitative', reverse, transcription, polymerase, chain, reaction, showed, that, 'VPA']), verbo([enhanced]), complemento(['GATA-2,', but, not, 'GATA-1,', messenger, 'RNA', expression, with, 'IL-3+SCF'])]). relacion([sujeto(['These', results, indicate, a, novel, role, for, 'VPA', in]), verbo([enhancing]), complemento([the, potential, of, 'IL-3', to, stimulate, megakaryopoiesis, as, well, as, erythropoiesis, and, suggest, a, new, therapeutic, approach, of, epigenetic, therapy, for, hematological, disease])]). relacion([sujeto(['The', authors]), verbo([report]), complemento([the, first, case, of, transient, myeloproliferative, disorder, '(', 'TMD)', in, a, neonate, with, trisomy, 12])]). relacion([sujeto(['The', condition]), verbo([has]), complemento([been, described, in, association, with, 'Down', syndrome, '(', trisomy, 21, ')', but, never, with, trisomy, 12])]). relacion([sujeto(['This', is, extremely, important, because, most, cases, of, 'TMD', resolve, spontaneously, within, a, few, weeks, to, months, and, do, not]), verbo([require]), complemento([treatment, other, than, supportive, measures])]). relacion([sujeto(['A', search, of, the, literature, did, not]), verbo([reveal]), complemento([any, similar, case])]). relacion([sujeto([')', as, an, injury, agent, for]), verbo([inducing]), complemento([transient, suppression, of, hematopoiesis, in, a, murine, experimental, model, during, 10, days])]). relacion([sujeto(['The', aim, of, this, study, focuses, on, erythropoietin, '(', 'EPO)', 'receptor,', 'GATA']), verbo([binding]), complemento([protein, 1, '(', globin, transcription, factor, 1, ')', '(', 'GATA-1)', and, erythroid, 'Krüppel-like', factor, '(', 'EKLF)', expressions, related, to, the, apoptotic, events, triggered, by, paclitaxel, in, bone, marrow, and, the, subsequent, in, vivo, erythropoietic, recovery])]). relacion([sujeto(['Results', showed, a, massive, impairment, of, erythropoiesis, early, post, paclitaxel, administration, '(', 1, -, 2, 'days),', which]), verbo([involved]), complemento([induction, of, high, 'Bax/Bcl-x(L)', 'ratio,', 'caspase-3', 'activation,', disruptions, of, the, medullar, niche, and, cell, death, by, both, apoptosis, and, necrosis])]). relacion([sujeto(['This', study]), verbo([suggests]), complemento([that, 'EPO', receptor, recovery, is, necessary, for, the, subsequent, bone, marrow, ability, to, accomplish, the, erythroid, program, through, the, modulation, of, apoptotic, and, survival, events, after, a, single, paclitaxel, insult])]). relacion([sujeto(['These', findings, contribute, to, new, insights, into, the, molecular, mechanisms]), verbo([involved]), complemento([during, in, vivo, erythropoiesis, post, paclitaxel, administration])]). relacion([sujeto(['Therefore,', the, detailed, knowledge, of, the, injury, elicited, by, this, drug, on, red, blood, cell, production, may]), verbo([have]), complemento([clinical, relevance, to, explore, new, therapeutic, approaches])]). relacion([sujeto(['Primary', myelofibrosis, '(', 'PMF)', belongs, to, the, 'Philadelphia-negative', myeloproliferative, neoplasms, and, is, a, hematological, disorder]), verbo([caused]), complemento([by, abnormal, function, of, the, hematopoietic, stem, cells])]). relacion([sujeto(['In', an, attempt, to, investigate, the, role, of, abnormal, megakaryocytopoiesis, in, the, pathogenesis, of, 'PMF,', several, transgenic, mouse, models]), verbo([have]), complemento([been, generated])]). relacion([sujeto(['These', models, are, based, either, on, mutations, that, interfere, with, the, extrinsic, '(', thrombopoietin, and, its, 'receptor,', 'MPL)', and, intrinsic, '(', the, 'GATA1', transcription, 'factor)', control, of, normal, 'megakaryocytopoiesis,', or, on, known, genetic, lesions]), verbo([associated]), complemento([with, the, human, disease])]). relacion([sujeto(['Here', we]), verbo([provide]), complemento([an, 'up-to-date', review, on, the, insights, into, the, pathobiology, of, human, 'PMF', achieved, by, studying, these, animal, 'models,', with, particular, emphasis, on, results, obtained, with, 'Gata1(low)', mice])]). relacion([sujeto(['Whereas', 'GATA1', is, known, to]), verbo([regulate]), complemento([the, p45, 'gene,', details, of, the, 'GATA1', contribution, to, the, spatiotemporal, expression, of, the, p45, gene, remain, to, be, elucidated])]). relacion([sujeto(['We', established, transgenic, mouse, lines]), verbo([expressing]), complemento([p45, under, 'G1HRD', regulation, and, crossed, the, mice, with, 'p45-null', mice])]). relacion([sujeto(['Compound', mutant, mice, displayed, normal, platelet, counts, and, no, sign, of, 'hemorrhage,', indicating, that, 'G1HRD']), verbo([has]), complemento([the, ability, to, express, p45, in, a, spatiotemporally, correct, manner])]). relacion([sujeto(['However,', deletion, of, 38, amino, acids, from, the, 'N-terminal', region, of, p45, abrogated, the, p45, rescue, 'function,']), verbo([suggesting]), complemento([the, presence, of, an, essential, transactivation, activity, in, the, region])]). relacion([sujeto(['The', 'G1HRD-p45', transgene, was, insufficient, for, complete, rescue, of, the, 'Gata1(Delta)(neo)(Delta)(HS)', 'megakaryocytes,']), verbo([suggesting]), complemento([that, 'GATA1', or, other, factors, regulated, by, 'GATA1', are, required, to, cooperate, with, p45, for, normal, megakaryopoiesis])]). relacion([sujeto(['This', study, thus]), verbo([provides]), complemento([a, unique, in, vivo, validation, of, the, hierarchical, relationship, between, 'GATA1', and, p45, in, megakaryocytes])]). relacion([sujeto(['Previously,', we]), verbo([have]), complemento([shown, that, overexpression, of, an, activated, mutant, of, signal, transducer, and, activator, of, 'transcription-5', '(', 'STAT5)', induces, 'erythropoiesis,', impaired, 'myelopoiesis,', and, an, increase, in, 'long-term', proliferation, of, human, hematopoietic, 'stem/progenitor', cells])]). relacion([sujeto(['Because', 'GATA1', is, a, key, transcription, factor]), verbo([involved]), complemento([in, 'erythropoiesis,', the, involvement, of, 'GATA1', in, 'STAT5-induced', phenotypes, was, studied, by, 'shRNA-mediated', knockdown, of, 'GATA1'])]). relacion([sujeto(['CD34(+)', cord, blood, cells, were, double, transduced, with, a, conditionally, active, 'STAT5', mutant, and, a, lentiviral, vector]), verbo([expressing]), complemento([a, short, hairpin, against, 'GATA1'])]). relacion([sujeto(['Interestingly,', early, cobblestone, formation, was, only, modestly, 'affected,', and, 'long-term', growth, of, 'STAT5-positive', cells, was]), verbo([increased]), complemento([in, the, absence, of, 'GATA1,', whereby, high, progenitor, numbers, were, maintained])]). relacion([sujeto(['Gene', expression, profiling, allowed, the, identification, of, 'GATA1-dependent', and, 'GATA1-independent', 'STAT5']), verbo([target]), complemento(['genes,', and, these, studies, revealed, that, several, 'proliferation-related', genes, were, 'up-regulated', by, 'STAT5', independent, of, 'GATA1,', whereas, several, erythroid, 'differentiation-related', genes, were, found, to, be, 'GATA1', as, well, as, 'STAT5', dependent])]). relacion([sujeto(['Eosinophil/basophil', '(', 'Eo/B)', progenitor, phenotype, and, function, in, cord, blood, '(', 'CB)', are]), verbo([associated]), complemento([with, atopic, risk, at, birth, and, infant, clinical, outcomes])]). relacion([sujeto(['Stimulation', of, the, 'non-adherent', mononuclear, cells, with, 'IL-5', resulted, in, early, 'up-regulation', of, 'GATA-1,', peaking, at, 48, 'h,', followed, by]), verbo([decreasing]), complemento([expression, and, 'down-regulation', by, 96, h])]). relacion([sujeto(['Total', 'IL-5R', alpha, expression, appeared, stable, over, the, 'time-course,']), verbo([mediated]), complemento([by, differential, expression, of, the, soluble, and, transmembrane, isoforms, '(', i])]). relacion([sujeto([',', initial]), verbo([increase]), complemento([in, the, transmembrane, contribution, followed, by, a, predominance, of, the, soluble, isoform, by, 48, -, 72, 'h)'])]). relacion([sujeto(['The', 'non-adherent', mononuclear, cell, population]), verbo([provides]), complemento([a, surrogate, signal, for, the, 'CD34+', progenitor, population])]). relacion([sujeto([1, and, 'GATA-1', is]), verbo([required]), complemento([for, proper, specification, of, the, mast, cell, 'lineage;', 'however,', in, the, myeloid, and, erythroid, 'lineages,', 'PU'])]). relacion([sujeto(['In', this, 'study,', we]), verbo([report]), complemento([a, transcriptional, network, in, which, 'PU'])]). relacion([sujeto([1, positively]), verbo([regulates]), complemento(['GATA-1', expression, in, mast, cell, development])]). relacion([sujeto(['Using', reporter, 'assays,', we, identify, an, enhancer, flanking, the, 'IB', exon, that, is]), verbo([activated]), complemento([by, 'PU'])]). relacion([sujeto([1, ',', possibly, in, concert, with, 'GATA-2,']), verbo([activates]), complemento(['GATA-1', expression, in, mast, cells, in, a, pathway, distinct, from, that, seen, in, the, erythroid, and, megakaryocytic, lineages])]). relacion([sujeto([cDC, maturation, was]), verbo([associated]), complemento([with, 'bell-shaped', changes, in, 'Gata1', expression, that, peaked, in, cDCs, precursors, from, blood])]). relacion([sujeto(['The', 'Gata1(low)', mutation, did, not, affect, 'Gata1', expression, in, cDC, precursors, and, these, cells]), verbo([expressed]), complemento([the, 'HS2-driven', 'reporter,', indicating, that, 'Gata1', expression, is, 'HS2-driven', in, these, cells])]). relacion([sujeto(['By', 'contrast,', the, 'Gata1(low)', mutation, reduced, 'Gata1', expression, in, mature, cDCs, and, these, cells, did, not]), verbo([express]), complemento(['GFP,', indicating, that, mature, cDCs, express, 'Gata1', driven, by, 'HS1'])]). relacion([sujeto(['In', 'blood,', the, number, of, cDC, precursors]), verbo([expressing]), complemento(['CD40/CD80', was, reduced, in, 'Gata1(low)', 'mice,', while, 'CD40(pos)/CD80(pos)', cDC, precursors, from, 'wild-type', mice, expressed, the, 'HS2-GFP', 'reporter,', suggesting, that, 'Gata1', expression, in, these, cells, is, both, 'HS1-', and, 'HS2-driven'])]). relacion([sujeto(['In', 'addition,', the, antigen, and, accessory, molecules, presentation, process]), verbo([induced]), complemento([by, lipopolysaccharide, in, ex, 'vivo-generated', 'wild-type', 'DC', was, associated, with, increased, acetylated, histone, 4, occupancy, of, 'HS1,', while, ex, 'vivo-generated', 'Gata1(low)', cDCs, failed, to, respond, to, 'lipopolysaccharide,', suggesting, that, 'HS1', activation, is, required, for, cDC, maturation])]). relacion([sujeto(['These', results, identify, a, dynamic, pattern, of, 'Gata1', regulation, that, switches, from, an, 'HS1', to, an, 'HS2-dependent', phase, during, the, maturation, of, cDCs]), verbo([associated]), complemento([with, the, 'antigen-presentation', process, in, the, blood])]). relacion([sujeto(['Our', retrospective, study]), verbo([reveals]), complemento([that, patients, with, mosaic, 'DS', and, 'AMKL', have, a, good, prognosis])]). relacion([sujeto(['We']), verbo([report]), complemento([here, a, novel, enhancer, activity, in, 5, '\'', 'HS1', that, appears, to, be, potent, in, transfected, 'K562', cells])]). relacion([sujeto(['Deletion', analyses, identified, a, core]), verbo([activating]), complemento([element, that, bound, to, 'GATA-1,', and, a, 'two-nucleotide', mutation, that, disrupted, 'GATA-1', binding, in, vitro, abrogated, 5, '\'', 'HS1', enhancer, activity, in, transfection, experiments])]). relacion([sujeto(['Using', an, 'NOD/SCID', 'model,', we]), verbo([found]), complemento([that, cells, initiating, 'DS-ML', 'engrafted,', disseminated, to, distant, bone, marrow, 'sites,', and, propagated, the, leukemic, clone, in, secondary, recipients])]). relacion([sujeto(['We']), verbo([found]), complemento([some, evidence, of, genomic, progression, with, 1, of, 9, 'DS-ML', samples, and, none, of, 11, 'TL', samples, harboring, a, mutation, of, 'N-RAS'])]). relacion([sujeto(['The', findings, of, this, pilot, study]), verbo([provide]), complemento([evidence, for, the, functional, impact, of, second, events, underlying, the, transformation, of, 'TL', into, 'DS-ML', and, a, needed, experimental, tool, for, the, functional, testing, of, these, promoting, events])]). relacion([sujeto(['Efforts']), verbo([have]), complemento([been, made, to, understand, how, erythroid, differentiation, is, 'regulated,', and, recent, discoveries, have, clarified, that, 'lineage-specific', transcription, factor, networks, are, essential, for, proper, differentiation, of, erythroid, cells])]). relacion([sujeto(['The', transcription, factors, 'GATA1', and, 'GATA2', are]), verbo([involved]), complemento([in, such, networks, that, regulate, erythroid, gene, expression])]). relacion([sujeto(['Gata1', and, 'Gata2', genes, are]), verbo([regulated]), complemento([by, multiple, transcription, 'factors,', including, their, own, products, 'GATA1', and, 'GATA2'])]). relacion([sujeto(['GATA1', and, 'GATA2']), verbo([recognize]), complemento([specific, regulatory, 'GATA', 'motifs,', and, their, expression, levels, change, dynamically, during, erythroid, 'differentiation,', leading, to, diversified, gene, expression, during, erythropoiesis])]). relacion([sujeto(['It']), verbo([has]), complemento([been, shown, in, transgenic, mouse, analyses, that, 'cis-acting', 'GATA', binding, motifs, are, critical, for, the, expression, of, 'Gata1', and, 'Gata2', genes])]). relacion([sujeto(['Furthermore,', expression, of, 'Gata1', and, 'Gata2', genes, along, with, a, set, of, erythroid, genes, appeared, to, be]), verbo([regulated]), complemento([by, 'GATA', factor, switching])]). relacion([sujeto(['The', factors, on, human, chromosome, 21, '(', 'Hsa21)', that]), verbo([confer]), complemento([this, predisposing, 'effect,', especially, in, synergy, with, consistently, mutated, transcription, factor, 'GATA1', '(', 'GATA1s),', remain, poorly, understood])]). relacion([sujeto(['We', identified, a, function, of, 'miR-125b-2', in]), verbo([increasing]), complemento([proliferation, and, 'self-renewal', of, human, and, mouse, megakaryocytic, progenitors, '(', 'MPs)', and, 'megakaryocytic/erythroid', progenitors, '(', 'MEPs)'])]). relacion([sujeto(['The', proproliferative, effect, of, 'miR-125b-2', on, 'MEPs', accentuated, the, 'Gata1s', 'mutation,', whereas, growth, of, 'DS-AMKL/TL', cells, was, impaired, upon, 'miR-125b', 'repression,']), verbo([suggesting]), complemento([synergism, during, leukemic, transformation, in, 'GATA1s-mutated', 'DS-AMKL/TL'])]). relacion([sujeto(['Integrative', transcriptome, analysis, of, hematopoietic, cells, upon, modulation, of, 'miR-125b', expression, levels, uncovered, a, set, of, 'miR-125b']), verbo([target]), complemento(['genes,', including, 'DICER1', and, 'ST18', as, direct, targets])]). relacion([sujeto(['Gene', 'Set', 'Enrichment', 'Analysis', revealed, that, this]), verbo([target]), complemento([gene, set, is, 'down-regulated', in, 'DS-AMKL', patients, highly, expressing, 'miR-125b'])]). relacion([sujeto(['Thus,', we, propose, 'miR-125b-2', as, a, positive, regulator, of, megakaryopoiesis, and, an, oncomiR]), verbo([involved]), complemento([in, the, pathogenesis, of, trisomy, 21, -, associated, megakaryoblastic, leukemia])]). relacion([sujeto(['To', identify, genetic, factors, that]), verbo([interact]), complemento([with, social, environments, to, impact, human, 'health,', we, used, a, bioinformatic, strategy, that, couples, expression, 'array-based', detection, of, environmentally, responsive, transcription, factors, with, in, silico, discovery, of, regulatory, polymorphisms, to, predict, genetic, loci, that, modulate, transcriptional, responses, to, stressful, environments])]). relacion([sujeto(['Tests', of, one, predicted, interaction, locus, in, the, human, 'IL6', promoter, '(', 'SNP', 'rs1800795)', verified, that, it]), verbo([modulates]), complemento([transcriptional, response, to, 'beta-adrenergic', activation, of, the, 'GATA1', transcription, factor, in, vitro])]). relacion([sujeto(['In', vivo, validation, studies, confirmed, links, between, adverse, social, conditions, and]), verbo([increased]), complemento([transcription, of, 'GATA1', target, genes, in, primary, 'neural,', 'immune,', and, cancer, cells])]). relacion([sujeto(['Epidemiologic', analyses, verified, the, health, significance, of, those, molecular, interactions, by, documenting]), verbo([increased]), complemento([10, -, year, mortality, risk, associated, with, 'late-life', depressive, symptoms, that, occurred, solely, for, homozygous, carriers, of, the, 'GATA1-sensitive', 'G', allele, of, rs1800795])]). relacion([sujeto(['Gating', of, 'depression-related', mortality, risk, by, 'IL6', genotype, pertained, only, to, 'inflammation-related']), verbo([causes]), complemento([of, death, and, was, associated, with, increased, chronic, inflammation, as, indexed, by, plasma, 'C-reactive', protein])]). relacion([sujeto(['DS', children]), verbo([have]), complemento([greatly, increased, rates, of, acute, lymphoblastic, leukemia, and, acute, megakaryoblastic, leukemia, '(', 'AMKL);', 'DS', newborns, present, with, transient, myeloproliferative, disorder, '(', 'TMD),', a, preleukemic, form, of, 'AMKL'])]). relacion([sujeto(['TMD', and, 'DS-AMKL', almost, always, carry, an, acquired, mutation, in, 'GATA1', resulting, in, exclusive, synthesis, of, a, truncated, protein, '(', 'GATA1s),']), verbo([suggesting]), complemento([that, both, trisomy, 21, and, 'GATA1', mutations, are, required, for, leukemogenesis])]). relacion([sujeto(['To']), verbo([gain]), complemento([further, understanding, of, how, 'Hsa21', contributes, to, hematopoietic, 'abnormalities,', we, examined, the, 'Tc1', mouse, model, of, 'DS,', which, carries, an, almost, complete, freely, segregating, copy, of, 'Hsa21,', and, is, the, most, complete, model, of, 'DS', available])]). relacion([sujeto(['We', show, that, although, 'Tc1', mice, do, not, develop, 'leukemia,', they]), verbo([have]), complemento([macrocytic, anemia, and, increased, extramedullary, hematopoiesis])]). relacion([sujeto(['Introduction', of, 'GATA1s', into, 'Tc1', mice, resulted, in, a, synergistic]), verbo([increase]), complemento([in, 'megakaryopoiesis,', but, did, not, result, in, leukemia, or, a, 'TMD-like', 'phenotype,', demonstrating, that, 'GATA1s', and, trisomy, of, approximately, 80, '%', of, 'Hsa21', perturb, megakaryopoiesis, but, are, insufficient, to, induce, leukemia])]). relacion([sujeto(['Precise', spatiotemporal, control, of, 'Gata1', expression, is]), verbo([required]), complemento([in, both, early, hematopoietic, progenitors, to, determine, 'erythroid/megakaryocyte', versus, 'granulocyte/monocyte', lineage, output, and, in, the, subsequent, differentiation, of, erythroid, cells, and, megakaryocytes])]). relacion([sujeto(['However,']), verbo([loss]), complemento([of, this, element, ablates, only, 'megakaryocytes,', implying, that, an, additional, element, has, erythroid, specificity])]). relacion([sujeto(['It']), verbo([binds]), complemento([an, activating, transcription, factor, complex, in, erythroid, cells, where, it, also, makes, physical, contact, with, the, 'Gata1', promoter])]). relacion([sujeto([5, in, embryonic, stem, cells]), verbo([has]), complemento([only, a, modest, effect, on, in, vitro, erythroid, 'differentiation,', whereas, loss, of, both, elements, ablates, both, primitive, and, definitive, erythropoiesis, with, an, almost, complete, loss, of, 'Gata1', expression])]). relacion([sujeto(['Surprisingly,', 'Gata2', expression, was, also, concomitantly, 'low,']), verbo([suggesting]), complemento([a, more, complex, interaction, between, these, 2, factors, than, currently, envisaged])]). relacion([sujeto([5, and, 'mHS-25/6', collectively]), verbo([regulate]), complemento([erythroid, 'Gata1', 'expression,', demonstrating, 'lineage-specific', differences, in, 'Gata1', 'cis-element', use, important, for, development, of, these, 2, cell, types])]). relacion([sujeto(['The', functions, of, parathyroid, 'hormone-related', protein, '(', 'PTHrP)', on, 'morphogenesis,', cell, 'proliferation,', 'apoptosis,', and, calcium, homeostasis]), verbo([have]), complemento([been, attributed, to, its, 'N', terminus])]). relacion([sujeto(['Evidence']), verbo([suggests]), complemento([that, many, of, these, effects, are, not, mediated, by, the, 'N', terminus, but, by, the, 'midregion,', a, nuclear, localization, sequence, '(', 'NLS),', and, 'C', terminus, of, the, protein])]). relacion([sujeto(['These', results, establish, that, the, 'midregion,', 'NLS,', and, 'C', terminus, of, 'PTHrP', are, crucial, for, the, commitment, of, osteogenic, and, hematopoietic, precursors, to, their, 'lineages,', and, for, 'survival,', and, many, of, the, effects, of, 'PTHrP', on, development, are, not]), verbo([mediated]), complemento([by, its, 'N', terminus])]). relacion([sujeto(['To', elaborate, further, the, 'DNA', elements, which, control, its, 'regulation,', we, used, genomic, tiling, microarrays, covering, 256, kb, of, the, human, 'SCL', locus, to, perform, a, concerted, analysis, of, chromatin, structure, and]), verbo([binding]), complemento([of, regulatory, proteins, in, human, haematopoietic, cell, lines])]). relacion([sujeto(['This', approach, allowed, us, to, characterise, further, or, redefine, known, human, 'SCL', regulatory, elements, and]), verbo([led]), complemento([to, the, identification, of, six, novel, elements, with, putative, regulatory, function, both, up, and, downstream, of, the, 'SCL', gene])]). relacion([sujeto(['They']), verbo([bind]), complemento([a, number, of, haematopoietic, transcription, factors, '(', 'GATA1,', 'E2A', 'LMO2,', 'SCL,', 'LDB1),', 'CTCF', or, components, of, the, transcriptional, machinery, and, are, associated, with, relevant, histone, 'modifications,', accessible, chromatin, and, low, nucleosomal, density])]). relacion([sujeto(['Functional', characterisation, shows, that, these, novel, elements, are, able, to]), verbo([enhance]), complemento([or, repress, 'SCL', promoter, 'activity,', have, endogenous, promoter, function, or, 'enhancer-blocking', insulator, function])]). relacion([sujeto(['However,', it, is, difficult, to, fractionate, living, eosinophils, by, flow, cytometry, because, these, granulocytes]), verbo([express]), complemento([multiple, cell, surface, markers, that, are, shared, by, other, cells, of, hematopoietic, or, 'non-hematopoietic', origin])]). relacion([sujeto(['To', fractionate, these, cell, 'types,', we, used, transgenic, mouse, lines, that]), verbo([express]), complemento([fluorescent, proteins, under, control, of, the, 'Gata1', gene, hematopoietic, regulatory, region, '(', 'Gata1-HRD),', which, is, exclusively, active, in, 'Gata1-expressing', hematopoietic, 'cells,', including, eosinophils])]). relacion([sujeto(['The', expression, of, these, 'eosinophil-specific', genes]), verbo([increased]), complemento([as, the, cells, differentiated])]). relacion([sujeto(['Here,', the, dynamics, of, the, composition, of, the, 'complex-in', 'particular,', the]), verbo([binding]), complemento([of, the, negative, regulators, 'Eto2', and, 'Mtgr1-are', 'studied,', in, the, context, of, their, 'genome-wide', targets])]). relacion([sujeto(['This', shows, that, the, complex]), verbo([acts]), complemento([almost, exclusively, as, an, 'activator,', binding, a, very, specific, combination, of, 'sequences,', with, a, positioning, relative, to, transcription, start, 'site,', depending, on, the, type, of, the, core, promoter])]). relacion([sujeto(['The', activation, is, accompanied, by, a, net]), verbo([decrease]), complemento([in, the, relative, binding, of, 'Eto2', and, 'Mtgr1'])]). relacion([sujeto(['A', 'Chromosome', 'Conformation', 'Capture', sequencing, '(', 3, 'C-seq)', assay, also, shows, that, the]), verbo([binding]), complemento([of, the, 'Ldb1', complex, marks, genomic, interaction, sites, in, vivo])]). relacion([sujeto(['This', establishes, the, 'Ldb1', complex, as, a, positive, regulator, of, the, final, steps, of, erythroid, differentiation, that]), verbo([acts]), complemento([through, the, shedding, of, negative, regulators, and, the, active, interaction, between, regulatory, sequences])]). relacion([sujeto(['The', 'X-linked', 'Gata1(low)', mutation, in, mice]), verbo([induces]), complemento(['strain-restricted', myeloproliferative, disorders, characterized, by, extramedullary, hematopoiesis, in, spleen, '(', 'CD1', and, 'DBA/2)', and, liver, '(', 'CD1', 'only)'])]). relacion([sujeto(['However,', progenitor, cells, prospectively, isolated, from, 'spleen,', but, not, from, 'marrow,', of, 'Gata1(low)', mice]), verbo([expressed]), complemento(['colony-forming', function, in, vitro])]). relacion([sujeto(['This', observation, indicates, that, 'Gata1(low)', hematopoiesis, is, favored, by, the, spleen, and, is, in, agreement, with, our, previous]), verbo([report]), complemento([that, removal, of, this, organ, induces, 'wild-type', hematopoiesis, in, heterozygous, 'Gata1(low/+)', females, '(', 'Migliaccio', et, al])]). relacion([sujeto(['To', clarify, if, rescue, of, 'wild-type', hematopoiesis, by, splenectomy]), verbo([prevented]), complemento([extramedullary, hematopoiesis, in, 'liver,', marrow, cytokine, expression, profile, and, liver, histopathology, of, splenectomized, 'Gata1(low/+)', females, were, investigated])]). relacion([sujeto(['Therefore,', in, the, absence, of, the, 'spleen,', 'Gata1(low)', hematopoiesis, is, supported, by, the, liver]), verbo([suggesting]), complemento([that, treatment, of, myelofibrosis, in, these, animals, requires, the, rescue, of, both, stem, cell, and, microenvironmental, functions])]). relacion([sujeto(['We']), verbo([found]), complemento([two, discrete, populations, of, thrombocytes, verified, by, 'morphology,', labeled, with, 'GFP', in, both, 'G1-GM2', and, 'TG(fli1:EGFP)y1', 'lines:', '(', 1, ')', the, more, intensely, labeled, 'GFP+', 'thrombocyte,', and, '(', 2, ')', the, less, intensely, labeled, 'GFP+', thrombocytes])]). relacion([sujeto(['These', results, showed, that, young, thrombocytes]), verbo([have]), complemento([higher, 'GATA1', promoter, 'activity,', while, mature, thrombocytes, have, more, 'FLI1', gene, promoter, transcription])]). relacion([sujeto(['This']), verbo([finding]), complemento([suggests, that, there, is, a, gradual, loss, of, 'GATA1', and, gain, of, 'FLI1', expression, as, the, thrombocytes, 'mature,', and, this, overexpression, of, 'FLI1', may, help, maintain, the, thrombocyte, lineage])]). relacion([sujeto(['Furthermore,', the, presence, of, transcriptional, factors, similar, to, those]), verbo([found]), complemento([in, megakaryocytes, raises, the, possibility, that, vertebrate, thrombocytes, may, be, the, forerunners, of, mammalian, megakaryocytes, 'and,', 'therefore,', could, serve, as, a, model, to, study, megakaryocyte, maturation])]). relacion([sujeto(['Children', with, 'Down', syndrome, '(', 'DS)']), verbo([have]), complemento([a, unique, form, of, acute, megakaryocytic, leukemia, '(', 'AMKL)', characterized, by, the, presence, of, mutations, in, the, 'GATA1', gene, leading, to, increased, chemosensitivity, and, a, favorable, outcome])]). relacion([sujeto(['The', patient, was, treated, according, to, the, 'DS-AML-regimen', but, his, disease, progressed, and]), verbo([he]), complemento([succumbed, 9, months, later])]). relacion([sujeto(['This', rare, case, of, 'DS', 'AMKL', without, a, 'GATA1', mutation, with, an, unfavorable, outcome]), verbo([suggests]), complemento([that, 'GATA1', testing, may, play, a, useful, role, in, initial, stratification])]). relacion([sujeto(['This', polymorphism, creates, a]), verbo([binding]), complemento([site, for, the, transcription, factor, 'GATA-1', inducing, a, second, 'GATA-1-binding', site, in, survivin, promoter])]). relacion([sujeto(['Transfection', of, 'wild-type', and, different, constitutively, active, 'GATA-1', mutants, '(', serine, 26, ',', 178, or, 310, ')', showed, that, only, 'phospho-serine', 26, 'GATA-1', was, able, to]), verbo([increase]), complemento([survivin, expression])]). relacion([sujeto(['This']), verbo([increase]), complemento([was, higher, in, 'G235A', than, in, 'G235G', cell, lines])]). relacion([sujeto(['Phospho-serine', 26, 'GATA-1']), verbo([bound]), complemento([directly, survivin, 'promoter,', with, a, stronger, interaction, in, 'G235A', than, in, 'G235G', polymorphism, indicating, that, both, 'GATA-1-binding', sites, are, functional])]). relacion([sujeto(['These', data, identify, 'GATA-1', as, a, key, feature, in, tumour, aggressiveness, by]), verbo([enhancing]), complemento([survivin, expression, and, delineate, its, targeting, as, a, possible, new, therapeutic, strategy, in, breast, carcinomas])]). relacion([sujeto(['Phenotypic', rescue, experiments]), verbo([have]), complemento([been, commonly, used, in, zebrafish, since, it, is, convenient, to, study, the, causality, of, mutant, phenotypes, just, by, injecting, mRNA, into, embryos])]). relacion([sujeto(['For', later, developmental, 'stages,', 'DNA', constructs, are, used, to]), verbo([express]), complemento([exogenous, 'genes,', while, it, is, usually, ineffective, owing, to, the, problem, of, mosaicism])]). relacion([sujeto(['As', a, model, 'case,', we, used, vlad, tepes, '(', 'vlt),', a, zebrafish, gata1, 'mutant,', whose, phenotypes]), verbo([have]), complemento([never, been, able, to, be, rescued, at, later, stages, by, transient, rescue, experiments])]). relacion([sujeto(['Nuclear', factors]), verbo([regulate]), complemento([the, development, of, complex, tissues, by, promoting, the, formation, of, one, cell, lineage, over, another])]). relacion([sujeto(['The', cofactor, 'FOG1']), verbo([interacts]), complemento([with, transcription, factors, 'GATA1', and, 'GATA2', to, control, erythroid, and, megakaryocyte, '(', 'MK)', differentiation])]). relacion([sujeto(['In', 'contrast,', 'FOG1', antagonizes, the, ability, of, 'GATA', factors, to]), verbo([promote]), complemento([mast, cell, '(', 'MC)', development])]). relacion([sujeto(['Normal', 'FOG1', function, in, 'late-stage', erythroid, cells, and, 'MK']), verbo([requires]), complemento([interaction, with, the, chromatin, remodeling, complex, 'NuRD'])]). relacion([sujeto(['Here,', we]), verbo([report]), complemento([that, mice, in, which, the, 'FOG1/NuRD', interaction, is, disrupted, '(', 'Fog(ki/ki))', produce, 'MK-erythroid', progenitors, that, give, rise, to, significantly, fewer, and, less, mature, 'MK', and, erythroid, colonies, in, vitro, while, retaining, multilineage, 'capacity,', capable, of, generating, 'MCs', and, other, myeloid, lineage, cells])]). relacion([sujeto(['Using', a, 'GATA1-dependent', committed, erythroid, cell, 'line,', select, 'MC', genes, were]), verbo([found]), complemento([to, be, occupied, by, 'NuRD,', suggesting, a, direct, mechanism, of, repression])]). relacion([sujeto(['Together,', these, observations]), verbo([suggest]), complemento([that, a, simple, heritable, silencing, mechanism, is, insufficient, to, permanently, repress, 'MC', genes])]). relacion([sujeto(['Instead,', the, continuous, presence, of, 'GATA1,', 'FOG1,', and, 'NuRD', is]), verbo([required]), complemento([to, maintain, lineage, fidelity, throughout, 'MK-erythroid', ontogeny])]). relacion([sujeto(['We', demonstrate, that, sumoylation, of, 'GATA-1', 'K137']), verbo([promotes]), complemento([transcriptional, activation, only, at, target, genes, requiring, the, coregulator, 'Friend', of, 'GATA-1', '(', 'FOG-1)'])]). relacion([sujeto(['A', mutation, of, 'GATA-1', 'V205G', that, disrupts, 'FOG-1']), verbo([binding]), complemento([and, 'K137', mutations, yielded, similar, 'phenotypes,', although, sumoylation, was, 'FOG-1', 'independent,', and, 'FOG-1', binding, did, not, require, sumoylation])]). relacion([sujeto(['While', 'FOG-1-', and, 'SUMO-1-dependent', genes, migrated, away, from, the]), verbo([nuclear]), complemento([periphery, upon, erythroid, 'maturation,', 'FOG-1-', and, 'SUMO-1-independent', genes, persisted, at, the, periphery])]). relacion([sujeto(['These', results, illustrate, a, mechanism, that, controls, 'trans-acting', factor, function, in, a, 'locus-specific', 'manner,', and, differentially]), verbo([regulated]), complemento([members, of, the, target, gene, ensemble, reside, in, distinct, subnuclear, compartments])]). relacion([sujeto(['Mutations', of, 'GATA1,']), verbo([leading]), complemento([to, aberrant, expression, of, a, truncated, form, of, 'GATA1', '(', called, 'GATA1s),', are, present, in, transient, leukaemia, '(', 'TL)', in, neonates, with, 'Down', syndrome])]). relacion([sujeto(['Interleukin-3,', stem, cell, factor, and, 'granulocyte-macrophage', 'colony-stimulating', factor, potently]), verbo([stimulated]), complemento([the, growth, of, 'TL', blast, progenitors, and, induced, differentiation, towards, 'basophil/mast', cell, 'lineages,', whereas, thrombopoietin, induced, differentiation, towards, megakaryocytes])]). relacion([sujeto(['GATA1s', was]), verbo([expressed]), complemento([in, 'TL', blasts, in, all, five, patients, examined, but, was, 'down-regulated', during, differentiation, induced, by, these, 'HGFs,', while, 'full-length', 'GATA1', was, not, expressed, throughout, the, culture])]). relacion([sujeto(['These', data, indicate, that, 'TL', blasts]), verbo([have]), complemento([the, potential, to, grow, and, differentiate, towards, particular, hematopoietic, lineages, in, the, presence, of, specific, 'HGFs', and, that, the, 'down-regulation', of, 'GATA1s', might, be, involved, in, blast, cell, differentiation])]). relacion([sujeto(['Recent', data]), verbo([suggest]), complemento([that, megakaryocytes, '(', 'MKs)', play, a, role, in, skeletal, homeostasis])]). relacion([sujeto(['In', vitro, and, in, vivo, data, show, that, 'MKs']), verbo([stimulate]), complemento([osteoblast, '(', 'OB)', proliferation, and, inhibit, osteoclast, '(', 'OC)', 'formation,', thus, favoring, net, bone, deposition])]). relacion([sujeto(['One', such, model, that, our, group]), verbo([has]), complemento([extensively, studied, is, 'GATA-1', deficient, mice])]). relacion([sujeto(['GATA-1', is, a, transcription, factor]), verbo([required]), complemento([for, normal, 'megakaryopoiesis,', and, mice, deficient, in, 'GATA-1', have, increases, in, immature, 'MK', number, and, a, striking, increase, in, bone, mass])]). relacion([sujeto(['While', the]), verbo([increased]), complemento([bone, mass, could, simply, be, a, result, of, increased, 'MK', 'number,', here, we, take, a, more, in, depth, look, at, the, 'MKs', of, these, mice, to, see, if, there, is, a, unique, factor, inherent, to, 'GATA-1', deficient, 'MKs', that, favors, increased, bone, deposition])]). relacion([sujeto(['We', show, that]), verbo([increased]), complemento(['MK', number, does, correspond, with, increased, 'OB', proliferation, and, decreased, 'OC', formation, that, stage, of, maturation, does, not, alter, the, effect, of, 'MKs', on, bone, cell, lineages, beyond, the, megakaryoblast, 'stage,', and, that, 'GATA-1', deficient, 'MKs', survive, longer, than, 'wild-type', controls])]). relacion([sujeto(['So', while]), verbo([increased]), complemento(['MK', number, in, 'GATA-1', deficient, mice, likely, contributes, to, the, high, bone, mass, 'phenotype,', we, propose, that, the, increased, longevity, of, this, lineage, also, plays, a, role])]). relacion([sujeto(['Down', syndrome, '(', 'DS),', which, occurs, once, in, every, 800, 'births,', is]), verbo([associated]), complemento([with, a, trisomy, on, locus, 21])]). relacion([sujeto(['Among', the, many, aberrations]), verbo([caused]), complemento([by, 'DS,', including, shortened, stature, and, distorted, 'facies,', are, several, blood, 'dyscrasias,', including, childhood, 'leukemias-namely,', acute, myeloid, leukemia, '(', 'AML)', and, acute, 'lymphoblastic,', or, 'lymphocytic,', leukemia, '(', 'ALL)'])]). relacion([sujeto(['ALL', is]), verbo([associated]), complemento([with, an, inherited, trisomy, 21, in, 'DS', children, '(', 'ALL-DS)', and, with, acquired, 'trisomies,', +, 21, ',', 8, ',', and, 13, ',', in, 'non-DS', children, '(', 'ALL-NDS)'])]). relacion([sujeto(['Other', mutations, are, the, gene, fusion, at, 'TEL/AML1,', and, a, new, mutation, 'found,', which, labels, the, 'Janus', 'Kinase', gene, or, 'JAK2', as, on, oncogenic, 'precursor,', which, when]), verbo([associated]), complemento([with, the, 'B-cell', precursor, gene, or, 'BCP', is, highly, leukomogenic])]). relacion([sujeto(['The', treatments, for, the, 2, groups]), verbo([have]), complemento([been, based, on, quality, of, 'risk,', with, 'ALL-DS', children, having, the, highest, risk, along, with, the, poorest, 'prognosis,', but, alterations, in, medication, regimens, have, brought, treatment, outcomes, to, near, equality])]). relacion([sujeto(['It', is, worthwhile, to, study, the, trisomy, 21, because, in, the, future, it, may]), verbo([provide]), complemento([an, understanding, of, all, blood, dyscrasias])]). relacion([sujeto(['In', vitro, studies]), verbo([have]), complemento([suggested, that, connexin43, '(', 'cx43)', expression, is, of, particular, importance, during, establishment, and, regeneration, of, the, mammalian, hematopoietic, system])]). relacion([sujeto(['In', this, 'study,', we, observed, that, zebrafish, cx43, is, not, only]), verbo([expressed]), complemento([in, the, 'eyes,', 'cerebellum,', 'heart,', and, 'vasculature,', but, also, 'expressed,', albeit, at, low, 'levels,', in, intermediate, cell, mass, '(', 'ICM,', the, primitive, hematopoietic, 'site)'])]). relacion([sujeto(['Knockdown', of, cx43]), verbo([leads]), complemento([to, vacuolization, in, the, wedge, of, the, 'ICM', and, an, apparent, reduction, in, the, number, of, circulating, blood, 'cells,', but, does, not, affect, their, cellular, morphology])]). relacion([sujeto(['Whole-mount', in, situ, hybridization, analysis, revealed, that, the, hemangioblastic, marker, 'flk-1', and, the, primitive, hematopoietic, markers, lmo2, and, scl, are, basically]), verbo([maintained]), complemento([at, normal, levels, in, cx43, morphant, embryos, at, 12, -, 13, &, 'nbsp;h', postfertilization, '(', 'hpf)', compared, with, the, 'con-MO', injected, embryos])]). relacion([sujeto(['The', transcriptional, 'co-factor', 'Friend', of, 'GATA1', '(', 'FOG-1)']), verbo([has]), complemento([been, shown, to, interact, with, subunits, of, the, nucleosome, remodelling, and, histone, deacetylase, '(', 'NuRD)', complex, through, a, specific, motif, located, at, its, 'N-terminus'])]). relacion([sujeto(['Homozygous', 'FOG-1(R3K5A)', mice, were]), verbo([found]), complemento([to, have, 'splenomegaly,', extramedullary, 'erythropoiesis,', granulocytosis, and, thrombocytopaenia, secondary, to, a, block, in, megakaryocyte, maturation])]). relacion([sujeto(['FOG-1(R3K5A/R3K5A)', megakaryocytes, and, erythroid, progenitors]), verbo([expressed]), complemento([increased, levels, of, 'GATA2,', showing, that, 'FOG-1/NuRD', interaction, is, required, for, the, earlier, described, '\'', 'GATA', 'Switch\''])]). relacion([sujeto(['In', 'addition,', ablation, of, 'FOG-1/NuRD', interaction]), verbo([led]), complemento([to, inappropriate, expression, of, mast, cell, and, 'eosinophil-specific', genes, in, the, megakaryocyte, and, erythroid, lineages])]). relacion([sujeto(['Chromatin', immunoprecipitation, experiments, revealed, that, the, 'NuRD', complex, was, not, properly]), verbo([recruited]), complemento([to, a, mast, cell, gene, promoter, in, 'FOG-1(R3K5A/R3K5A)', 'megakaryocytes,', suggesting, that, 'FOG-1/NuRD', interaction, is, required, for, the, direct, suppression, of, mast, cell, gene, expression])]). relacion([sujeto(['Down', syndrome, is, characterized, by, multiple, phenotypic, manifestations]), verbo([associated]), complemento([with, trisomy, of, chromosome, 21])]). relacion([sujeto(['The', transient, myeloproliferative, disorder, and, acute, megakaryocytic, leukemia]), verbo([associated]), complemento([with, 'Down', syndrome, are, uniquely, associated, with, mutations, in, the, transcription, factor, 'GATA1;', 'however,', the, identity, of, trisomic, genes, on, chromosome, 21, that, predispose, to, these, hematologic, disorders, remains, unknown])]). relacion([sujeto(['Our', data]), verbo([provide]), complemento([genetic, evidence, establishing, the, need, for, 'Erg', trisomy, for, myeloproliferation, in, 'Ts(17(16))65Dn', mice, and, imply, that, increased, 'ERG', gene, dosage, may, be, a, key, consequence, of, trisomy, 21, that, can, predispose, to, malignant, hematologic, disorders, in, 'Down', syndrome])]). relacion([sujeto(['Expression', of, a, 'CALM-AF10', transgene, results, in, 'leukemia,', with, prolonged, latency, and, incomplete, 'penetrance,']), verbo([suggesting]), complemento([that, additional, events, are, necessary, for, leukemic, transformation])]). relacion([sujeto(['A', total, of, 26, '%', '(', 11, of, 42, ')', of, the, mice, had, retroviral, integrations, near, 'Zeb2,', a, transcriptional, corepressor]), verbo([leading]), complemento([to, overexpression, of, the, 'Zeb2-transcript'])]). relacion([sujeto(['A', total, of, 91, '%', '(', 10, of, 11, ')', of, mice, with, 'Zeb2', insertions, developed, 'B-lineage', acute, lymphoblastic, 'leukemia,']), verbo([suggesting]), complemento([that, 'Zeb2', activation, promotes, the, transformation, of, 'CALM-AF10', hematopoietic, precursors, toward, 'B-lineage', leukemias])]). relacion([sujeto(['More', than, half, of, the, mice, with, 'Zeb2', integrations, also, had, 'Nf1', 'integrations,']), verbo([suggesting]), complemento([cooperativity, among, 'CALM-AF10,', 'Zeb2,', and, 'Ras', pathway, mutations])]). relacion([sujeto(['Three', mutations, were, 'identified,', all, of, which, occurred, in, mice, with, 'Zeb2', 'integrations,', consistent, with, the, hypothesis, that, 'Zeb2', and, 'Ras', pathway, activation]), verbo([promotes]), complemento(['B-lineage', leukemic, transformation, in, concert, with, 'CALM-AF10'])]). relacion([sujeto(['Gfi-1B', is, a, transcriptional, repressor, that, is, crucial, for, erythroid, 'differentiation:', inactivation, of, the, 'GFI1B', gene, in, mice]), verbo([leads]), complemento([to, embryonic, death, due, to, failure, to, produce, differentiated, red, cells])]). relacion([sujeto(['Accordingly,', 'GFI1B', expression, is, tightly]), verbo([regulated]), complemento([during, 'erythropoiesis,', but, the, mechanisms, involved, in, such, regulation, remain, partially, understood])]). relacion([sujeto(['HMGB2']), verbo([binds]), complemento([to, the, 'GFI1B', promoter, in, vivo, and, 'up-regulates', its, 'trans-activation', most, likely, by, enhancing, the, binding, of, 'Oct-1', 'and,', to, a, lesser, 'extent,', of, 'GATA-1', and, 'NF-Y', to, the, 'GFI1B', promoter])]). relacion([sujeto(['HMGB2', expression]), verbo([increases]), complemento([during, erythroid, differentiation, concomitantly, to, the, increase, of, 'GfI1B', transcription])]). relacion([sujeto(['Importantly,', knockdown, of, 'HMGB2', in, immature, hematopoietic, progenitor, cells]), verbo([leads]), complemento([to, decreased, 'Gfi-1B', expression, and, impairs, their, erythroid, differentiation])]). relacion([sujeto([1, is, strongly]), verbo([associated]), complemento([with, 'Friend', 'virus-induced', erythroleukemia])]). relacion([sujeto([1]), verbo([inhibits]), complemento([erythroid, differentiation, by, binding, to, and, inhibiting, 'GATA-1'])]). relacion([sujeto([1, also, may, be]), verbo([involved]), complemento([in, controlling, proliferation, of, erythroid, cells])]). relacion([sujeto(['We']), verbo([reported]), complemento([previously, that, the, 'G(1)', 'phase-specific', 'cyclin-dependent', kinase, 6, '(', 'CDK6)', also, blocks, erythroid, differentiation])]). relacion([sujeto(['We', now]), verbo([report]), complemento([that, 'PU'])]). relacion([sujeto([1, directly]), verbo([stimulates]), complemento([transcription, of, the, cdk6, gene, in, both, normal, erythroid, progenitors, and, erythroleukemia, 'cells,', as, well, as, in, macrophages])]). relacion([sujeto([1, coordinates, proliferation, and, differentiation, in, immature, erythroid, cells, by]), verbo([inhibiting]), complemento([the, 'GATA-1-mediated', gene, expression, program, and, also, by, regulating, expression, of, genes, that, control, progression, through, the, 'G(1)', phase, of, the, cell, 'cycle,', the, period, during, which, the, decision, to, differentiate, is, made])]). relacion([sujeto(['The', transcription, factor, 'GATA-1', is]), verbo([required]), complemento([for, terminal, erythroid, maturation, and, functions, as, an, activator, or, repressor, depending, on, gene, context])]). relacion([sujeto(['Yet', its, in, vivo, site, selectivity, and, ability, to, distinguish, between]), verbo([activated]), complemento([versus, repressed, genes, remain, incompletely, understood])]). relacion([sujeto(['Bound', and, differentially]), verbo([expressed]), complemento([genes, contain, a, greater, number, of, 'GATA-binding', 'motifs,', a, higher, frequency, of, palindromic, 'GATA', 'sites,', and, closer, occupancy, to, the, transcriptional, start, site, versus, nondifferentially, expressed, genes])]). relacion([sujeto(['Moreover,', we, show, that, the, transcription, factor, 'Zbtb7a', occupies, 'GATA-1-bound', regions, of, some, direct, 'GATA-1']), verbo([target]), complemento(['genes,', that, the, presence, of, 'SCL/TAL1', helps, distinguish, transcriptional, activation, versus, 'repression,', and, that, polycomb, repressive, complex, 2, '(', 'PRC2)', is, involved, in, epigenetic, silencing, of, a, subset, of, 'GATA-1-repressed', genes])]). relacion([sujeto(['These', data]), verbo([provide]), complemento([insights, into, 'GATA-1-mediated', gene, regulation, in, vivo])]). relacion([sujeto(['GATA', factors]), verbo([interact]), complemento([with, simple, 'DNA', motifs, '(', 'WGATAR)', to, regulate, critical, 'processes,', including, 'hematopoiesis,', but, very, few, 'WGATAR', motifs, are, occupied, in, genomes])]). relacion([sujeto(['Coupled', with, genetic, complementation, analysis, and, transcriptional, 'profiling,', these, studies, revealed, a, rich, collection, of]), verbo([targets]), complemento([containing, a, characteristic, binding, motif, of, greater, complexity, than, 'WGATAR'])]). relacion([sujeto(['Mechanistic', analyses]), verbo([provided]), complemento([evidence, for, crossregulatory, and, autoregulatory, interactions, among, components, of, this, 'complex,', including, 'GATA-2', induction, of, the, hematopoietic, corepressor, 'ETO-2', and, an, 'ETO-2-negative', autoregulatory, loop])]). relacion([sujeto(['GATA', transcription, factors]), verbo([interact]), complemento([with, 'FOG', proteins, to, regulate, tissue, development, by, activating, and, repressing, transcription])]). relacion([sujeto(['FOG-1', '(', 'ZFPM1),', a, 'co-factor', for, the, haematopoietic, factor, 'GATA-1,']), verbo([binds]), complemento([to, the, 'NuRD', 'co-repressor', complex, through, a, conserved, 'N-terminal', motif])]). relacion([sujeto(['Surprisingly,', we, detected, 'NuRD', components, at, both, repressed, and, active, 'GATA-1/FOG-1']), verbo([target]), complemento([genes, in, vivo])]). relacion([sujeto(['In', 'addition,', while, 'NuRD', is]), verbo([required]), complemento([for, transcriptional, repression, in, certain, 'contexts,', we, show, a, direct, requirement, of, 'NuRD', also, for, 'FOG-1-dependent', transcriptional, activation])]). relacion([sujeto(['Gene', expression, analysis, in, primary, mutant, erythroid, cells, and, megakaryocytes, '(', 'MKs)', revealed, an, essential, function, for, 'NuRD', during, both, the, repression, and, activation, of, select, 'GATA-1/FOG-1']), verbo([target]), complemento([genes])]). relacion([sujeto(['These', results, show, that, 'NuRD', is, a, critical, 'co-factor', for, 'FOG-1', and, underscore, the, versatile, use, of, 'NuRD', by, 'lineage-specific', transcription, factors, to]), verbo([activate]), complemento([and, repress, gene, transcription, in, the, appropriate, cellular, and, genetic, context])]). relacion([sujeto(['Earlier', studies]), verbo([have]), complemento([described, the, cellular, changes, that, happen, during, recovery, from, irradiation, by, means, of, histology])]). relacion([sujeto(['We']), verbo([have]), complemento([earlier, generated, gene, expression, profiles, during, induction, of, spermatogenesis, in, mouse, postnatal, developing, testes, and, found, a, correlation, between, profiles, and, the, expressing, cell, types])]). relacion([sujeto(['Irradiation', of, mice, testis, created, a, gap, in, 'spermatogenesis,', which, was, initiated, by]), verbo([loss]), complemento([of, 'A1', to, 'B-spermatogonia', and, lasted, for, approximately, 10, days])]). relacion([sujeto(['The', data, indicates, that, recovery, of, spermatogenesis, can, be, monitored, by, means, of, gene, 'expression,', which, could, aid, in, designing, radiation, treatment, regimes, for, cancer, patients]), verbo([leading]), complemento([to, better, restoration, of, spermatogenesis])]). relacion([sujeto(['We', describe, a, 'patient,', who, developed, during, the, first, week, of, life, petechiae, and, hematomas]), verbo([caused]), complemento([by, severe, thrombocytopenia, and, gastrointestinal, bleeding, due, to, multiple, small, gastric, hemangiomata])]). relacion([sujeto(['In', vitro, culturing, of, normal, 'CD34', cells, with, purified, patient, 'Igs', showed, a]), verbo([decreased]), complemento([number, of, megakaryocyte, colonies, but, an, increased, overall, size, of, the, colonies, compared, with, control, 'Igs'])]). relacion([sujeto(['In', 'conclusion,', this, study, is, the, first]), verbo([report]), complemento([of, an, 'anti-GATA1', autoantibody, leading, to, severe, thrombocytopenia, and, gastrointestinal, bleeding, from, multiple, pinpoint, hemangiomata])]). relacion([sujeto(['Experiments', in, multiple, model, systems]), verbo([have]), complemento([emphasized, the, importance, of, the, 'GATA', family, members, 4, -, 6, in, the, development, of, the, endoderm, and, mesoderm])]). relacion([sujeto(['We']), verbo([have]), complemento([generated, a, new, 'Gata5', mutant, allele, lacking, exons, 2, and, 3, that, encodes, both, zinc, finger, domains, '(', 'Gata5(tm)(2)(Eem)),', and, we, show, that, although, 'Gata5(-/-)', mice, are, 'viable,', 'Gata4(+/-)5(-/-)', mutants, die, at, 'mid-gestation', and, exhibit, profound, cardiovascular, 'defects,', including, abnormalities, of, cardiomyocyte, proliferation, and, cardiac, chamber, maturation])]). relacion([sujeto(['The', transcription, factor, 'GATA1']), verbo([regulates]), complemento([an, extensive, program, of, gene, activation, and, repression, during, erythroid, development])]). relacion([sujeto(['However,', the]), verbo([associated]), complemento(['mechanisms,', including, the, contributions, of, distal, versus, proximal, 'cis-regulatory', 'modules,', 'co-occupancy', with, other, transcription, 'factors,', and, the, effects, of, histone, 'modifications,', are, poorly, understood])]). relacion([sujeto(['Virtually', all, occupied, 'DNA', segments]), verbo([have]), complemento([high, levels, of, 'H3K4', monomethylation, and, low, levels, of, 'H3K27me3', around, the, canonical, 'GATA', binding, 'motif,', regardless, of, whether, the, nearby, gene, is, induced, or, repressed])]). relacion([sujeto(['Induced', genes, tend, to, be]), verbo([bound]), complemento([by, 'GATA1', close, to, the, transcription, start, site, '(', most, frequently, in, the, first, 'intron),', have, multiple, 'GATA1-occupied', segments, that, are, also, bound, by, 'TAL1,', and, show, evolutionary, constraint, on, the, 'GATA1-binding', site, motif])]). relacion([sujeto(['In', 'contrast,', repressed, genes, are, further, away, from, 'GATA1-occupied', 'segments,', and, a, subset, shows, reduced, 'TAL1', occupancy, and]), verbo([increased]), complemento(['H3K27me3', at, the, transcription, start, site])]). relacion([sujeto(['Our', data, expand, the, repertoire, of, 'GATA1', action, in, erythropoiesis, by, defining, a, new, cohort, of]), verbo([target]), complemento([genes, and, determining, the, spatial, distribution, of, 'cis-regulatory', modules, throughout, the, genome])]). relacion([sujeto(['In', 'addition,', we, begin, to, establish, functional, criteria, and, mechanisms, that, distinguish, 'GATA1', activation, from, repression, at, specific]), verbo([target]), complemento([genes])]). relacion([sujeto(['By', 'contrast,', in, the, erythroid, 'lineage,', 'Gata1', mRNA, was]), verbo([expressed]), complemento([abundantly, utilizing, alternative, first, exons])]). relacion([sujeto(['Especially,', the, 'IEb/c', and, newly, identified, 'IEd', exons, were]), verbo([transcribed]), complemento([at, a, level, comparable, with, that, of, the, 'IE', exon, in, control, mice])]). relacion([sujeto(['The', present, study, demonstrates, that, the, 'IE', exon, is, instrumental, to, adult, erythropoiesis, by]), verbo([regulating]), complemento([the, proper, level, of, transcription, and, selecting, the, correct, transcription, start, site, of, the, 'Gata1', gene])]). relacion([sujeto(['Suppression', of, programmed, cell, death, is, also, thought, to, be, critical, for, this, 'process;', 'however,', the, link, between, these, two, features, of, erythropoiesis]), verbo([has]), complemento([remained, elusive])]). relacion([sujeto(['Here,', we, show, that, the, 'POZ-Krüppel', family, transcription, 'factor,', 'LRF', '(', also, known, as, 'Zbtb7a/Pokemon),', is, a, direct]), verbo([target]), complemento([of, 'GATA1', and, plays, an, essential, antiapoptotic, role, during, terminal, erythroid, differentiation])]). relacion([sujeto(['We']), verbo([find]), complemento([that, loss, of, 'Lrf', leads, to, lethal, anemia, in, 'embryos,', due, to, increased, apoptosis, of, 'late-stage', erythroblasts])]). relacion([sujeto(['This', programmed, cell, death, is, 'Arf', and, p53, independent, and, is, instead]), verbo([mediated]), complemento([by, upregulation, of, the, proapoptotic, factor, 'Bim'])]). relacion([sujeto(['In', strong, support, of, this, 'mechanism,', genetic, 'Bim']), verbo([loss]), complemento([delays, the, lethality, of, 'Lrf-deficient', embryos, and, rescues, their, anemia, phenotype])]). relacion([sujeto(['Thus,', our, data, define, a, key, transcriptional, cascade, for, effective, 'erythropoiesis,', whereby, 'GATA-1']), verbo([suppresses]), complemento(['BIM-mediated', apoptosis, via, 'LRF'])]). relacion([sujeto(['The', transcription, factor, 'Gata1', is]), verbo([required]), complemento([for, the, development, of, erythrocytes, and, megakaryocytes])]). relacion([sujeto(['Previous', studies, with, a, complementation, rescue, approach, showed, that, the, zinc, finger, domains, are]), verbo([required]), complemento([for, both, primitive, and, definitive, hematopoiesis])]). relacion([sujeto(['Here', we]), verbo([report]), complemento([a, novel, zebrafish, gata1, mutant, with, an, 'N-ethyl-N-nitrosourea-induced', point, mutation, in, the, 'C-finger', '(', 'gata1(T301K))'])]). relacion([sujeto(['The', 'Gata1', protein, with, this, mutation]), verbo([bound]), complemento([to, its, 'DNA', target, sequence, with, reduced, affinity, and, transactivated, inefficiently, in, a, reporter, assay])]). relacion([sujeto(['gata1(T301K/T301K)', fish, had, a]), verbo([decreased]), complemento([number, of, erythrocytes, during, primitive, hematopoiesis, but, normal, adult, hematopoiesis])]). relacion([sujeto(['We', crossed, the, 'gata1(T301K/T301K)', fish, with, those, carrying, the, 'R339X', 'mutation,', also, known, as, vlad, tepes, '(', 'vlt),', which, abolishes, 'DNA']), verbo([binding]), complemento([and, transactivation, activities])]). relacion([sujeto(['As', we]), verbo([reported]), complemento(['previously,', 'gata1(vlt/vlt)', embryos, were, &, 'quot;bloodless"', and, died, approximately, 11, to, 15, days, after, fertilization])]). relacion([sujeto(['Our', findings]), verbo([suggest]), complemento([that, the, impact, of, 'Gata1', on, hematopoiesis, correlates, with, its, 'DNA-binding', ability, and, that, primitive, hematopoiesis, is, more, sensitive, to, reduction, in, 'Gata1', function, than, definitive, hematopoiesis])]). relacion([sujeto([1]), verbo([bind]), complemento([each, other, on, 'DNA', to, block, transcriptional, programs, of, undesired, lineage, during, hematopoietic, commitment])]). relacion([sujeto([1, are, blocked, at, the, blast, stage, but]), verbo([respond]), complemento([to, molecular, removal, '(', 'downregulation)', of, 'PU'])]). relacion([sujeto([1, or, addition, '(', 'upregulation)', of, 'GATA-1', by]), verbo([inducing]), complemento([terminal, erythroid, differentiation])]). relacion([sujeto([1, in, 'MEL', 'cells,', we]), verbo([have]), complemento([conditionally, activated, a, transgenic, 'PU'])]). relacion([sujeto([1, -, dependent, transcriptome, negatively]), verbo([regulated]), complemento([by, 'GATA-1', in, 'MEL', 'cells,', including, 'CCAAT/enhancer', binding, protein, alpha, '(', 'Cebpa)', and, 'core-binding', 'factor,', beta, subunit, '(', 'Cbfb),', which, encode, two, key, hematopoietic, transcription, factors])]). relacion([sujeto([1]), verbo([target]), complemento([genes])]). relacion([sujeto([1, and, 'GATA-1']), verbo([involves]), complemento([quantitative, increases, in, a, transcriptionally, active, chromatin, 'mark:', acetylation, of, histone, 'H3K9'])]). relacion([sujeto([1, or, inhibition, of, 'GATA-1', efficiently, reverses, the, transcriptional, block, imposed, by, 'GATA-1', and]), verbo([leads]), complemento([to, the, activation, of, a, myeloid, transcriptional, program, directed, by, 'PU'])]). relacion([sujeto(['Splenectomized', mice]), verbo([express]), complemento([progressively, increased, numbers, of, platelets, in, the, blood, and, reduced, numbers, of, megakaryocytes, in, the, marrow, with, age])]). relacion([sujeto(['The', megakaryocytes, in, the, marrow, of, these, animals]), verbo([express]), complemento([reduced, levels, of, 'Gata1,', a, transcription, factor, necessary, for, their, maturation])]). relacion([sujeto(['In', 'addition,', the, marrow, from, these, animals]), verbo([expresses]), complemento([greater, levels, of, cytokines, '(', 'TGF-beta,', 'PDGF-alpha,', and, 'VEGF)', known, to, be, produced, at, high, levels, by, megakaryocytes, expressing, reduced, levels, of, 'Gata1'])]). relacion([sujeto(['This', high, level, of, cytokine, expression, is, in, turn]), verbo([associated]), complemento([with, active, osteoblast, proliferation, localized, to, areas, of, the, 'femur,', where, megakaryocytes, expressing, reduced, 'Gata1', levels, are, also, found])]). relacion([sujeto(['These', results, confirm, the, role, of, megakaryocytes, as, regulator, of, bone, formation, in, mice, and]), verbo([suggest]), complemento([that, a, 'cross-talk', between, the, spleen, and, marrow, may, regulate, the, total, numbers, of, hemopoietic, niches, present, in, an, animal])]). relacion([sujeto(['Although', early, studies, showed, that, hematopoietic, stem, cells, choose, either, the, 'myeloid-erythroid', or, the, lymphoid, 'pathway,', recent, data]), verbo([suggest]), complemento([that, 'myelo-lymphoid', precursors, lacking, erythroid, potential, exist, in, early, hematopoiesis, before, cells, are, fully, committed, to, the, lymphoid, lineage])]). relacion([sujeto(['Injection', with, 'jak2a(V581F)', mRNA, significantly]), verbo([increased]), complemento(['erythropoiesis,', as, enumerated, by, flow, cytometry, based, on, 'gfp(+)', population, in, dissociated, 'Tg(gata1:gfp)', embryos])]). relacion([sujeto([26, ')', and]), verbo([increased]), complemento([stat5, phosphorylation])]). relacion([sujeto(['The', zebrafish, 'jak2a(V581F)', model, shared, many, features, with, human, 'PV', and, might]), verbo([provide]), complemento([us, with, mechanistic, insights, of, this, disease])]). relacion([sujeto(['DNA', sequence, motifs, and, epigenetic, modifications, contribute, to, specific]), verbo([binding]), complemento([by, a, transcription, 'factor,', but, the, extent, to, which, each, feature, determines, occupancy, in, vivo, is, poorly, understood])]). relacion([sujeto(['Combining', motifs, to, pair, a, 'WGATAR', motif, with, a]), verbo([binding]), complemento([site, motif, for, 'GATA1,', 'EKLF', or, 'SP1', improves, discriminative, power])]). relacion([sujeto(['Combining', primary, sequence, and, epigenetic, determinants, captures, 52, '%', of, the, 'GATA1-occupied', 'DNA', segments, and, substantially]), verbo([increases]), complemento([the, 'specificity,', to, one, out, of, seven, segments, with, the, required, motif, combination, and, epigenetic, signals, being, bound])]). relacion([sujeto(['Transcription', of, the, 'HDAC1', gene, was, repressed, by, 'CCAAT/enhancer']), verbo([binding]), complemento([proteins, during, myeloid, 'differentiation,', and, activated, by, 'GATA-1', during, 'erythro-megakaryocytic', differentiation])]). relacion([sujeto(['Small', interfering, 'RNA-mediated', knockdown, of, 'HDAC1']), verbo([enhanced]), complemento([myeloid, differentiation, in, immature, hematopoietic, cell, lines, and, perturbed, erythroid, differentiation, in, progenitor, cells])]). relacion([sujeto(['These', findings]), verbo([suggest]), complemento([that, 'HDAC', is, not, merely, an, auxiliary, factor, of, genetic, elements, but, plays, a, direct, role, in, the, cell, fate, decision, of, hematopoietic, progenitors])]). relacion([sujeto(['The']), verbo([nuclear]), complemento([protein, 'FOG-1', binds, transcription, factor, 'GATA-1', to, facilitate, erythroid, and, megakaryocytic, maturation])]). relacion([sujeto(['However,', little, is, known, about, the, function, of, 'FOG-1', during, myeloid, and, lymphoid, development, or, how, 'FOG-1', expression, is]), verbo([regulated]), complemento([in, any, tissue])]). relacion([sujeto(['Zebrafish', 'FOG-1', is]), verbo([expressed]), complemento([in, early, hematopoietic, 'cells,', as, well, as, 'heart,', 'viscera,', and, paraspinal, 'neurons,', suggesting, that, it, has, multifaceted, functions, in, organogenesis])]). relacion([sujeto(['We']), verbo([found]), complemento([that, 'FOG-1', is, dispensable, for, endoderm, specification, but, is, required, for, endoderm, patterning, affecting, the, expression, of, 'late-stage', 'T-cell', 'markers,', independent, of, 'GATA-1'])]). relacion([sujeto(['The', suppression, of, 'FOG-1,', in, the, presence, of, normal, 'GATA-1', 'levels,']), verbo([induces]), complemento([severe, anemia, and, thrombocytopenia, and, expands, 'myeloid-progenitor', 'cells,', indicating, that, 'FOG-1', is, required, during, 'erythroid/myeloid', commitment])]). relacion([sujeto(['To', functionally, interrogate, whether, 'GATA-1']), verbo([regulates]), complemento(['FOG-1', in, 'vivo,', we, used, bioinformatics, combined, with, transgenic, assays])]). relacion([sujeto(['Two', major, pathways, of, human, myeloid, dendritic, cell, '(', 'DC)', subset, differentiation]), verbo([have]), complemento([previously, been, delineated])]). relacion([sujeto(['Langerhans', cells, '(', 'LCs)', reside, in, epithelia, in, the, steady, 'state,', whereas, monocytes, can]), verbo([provide]), complemento([dendritic, cells, '(', 'DCs)', on, demand, in, response, to, inflammatory, signals])]). relacion([sujeto(['Here,', we, demonstrate, that, the, vitamin, 'D(3)', receptor, '(', 'VDR)', is]), verbo([induced]), complemento([by, transforming, growth, factor, beta1, during, 'LC', lineage, commitment, and, exerts, a, positive, role, during, 'LC', generation])]). relacion([sujeto(['GATA-1', is]), verbo([induced]), complemento([by, 'IL-4', in, moDCs])]). relacion([sujeto(['Forced', inducible, expression, of, 'GATA-1', mimics, 'IL-4', in, redirecting, moDC, differentiation, and, vice, 'versa,', 'GATA-1', knockdown]), verbo([arrests]), complemento([moDC, differentiation, at, the, monocyte, stage])]). relacion([sujeto(['In', 'summary,', human, myeloid, 'DC', subset, differentiation, is, inversely]), verbo([regulated]), complemento([by, 'GATA-1', and, 'VDR'])]). relacion([sujeto(['GATA-1']), verbo([mediates]), complemento([the, repression, of, 'VDR', and, enables, 'IL-4-dependent', moDC, differentiation])]). relacion([sujeto(['Conversely,', 'VDR', is]), verbo([induced]), complemento([downstream, of, transforming, growth, factor, beta1, and, is, functionally, involved, in, promoting, 'LC', differentiation])]). relacion([sujeto(['DS', children]), verbo([have]), complemento([a, approximately, 10, -, to, 20, -, fold, higher, risk, for, developing, acute, lymphoblastic, leukemia, and, acute, myeloid, leukemia, '(', 'AML),', as, compared, with, 'non-DS', 'children,', although, they, do, not, have, a, uniformly, increased, risk, of, developing, solid, tumors])]). relacion([sujeto(['DS', children, also, develop, 'AML', with, unique, features, and]), verbo([have]), complemento([a, 500, -, fold, increased, risk, of, developing, the, 'AML', 'subtype,', acute, megakaryocytic, leukemia, '(', 'AMkL;', 'M7)'])]). relacion([sujeto(['In', 'addition,', somatic, mutations, of, the, 'GATA1', gene]), verbo([have]), complemento([been, detected, in, nearly, all, 'DS', 'TMD', and, 'AMkL', cases, and, not, in, leukemia, cases, in, 'non-DS', children])]). relacion([sujeto(['Examining', leukemogenesis, in, 'DS', children, may, identify, factors, linked, to, the, general, development, of, childhood, leukemia, and]), verbo([lead]), complemento([to, potential, new, therapeutic, strategies, to, fight, this, disease])]). relacion([sujeto(['Previously', published, data]), verbo([suggested]), complemento([that, the, promoter, regions, of, 'alpha-globin', genes, contain, the, complete, information, for, proper, developmental, regulation])]). relacion([sujeto(['We', also]), verbo([found]), complemento([that, 'DNA', methylation, and, histone, deacetylation, play, key, roles, in, silencing, the, expression, of, the, embryonic, pi, gene, in, definitive, erythrocytes])]). relacion([sujeto(['However,', 'drug-mediated', reactivation, of, the, embryonic, gene, during, definitive, erythropoiesis, dramatically, impaired, the, expression, of, the, adult, 'genes,']), verbo([suggesting]), complemento([gene, competition, or, interference, for, enhancer, elements])]). relacion([sujeto(['Erythrocyte', membrane, protein, genes, serve, as, excellent, models, of, complex, gene, locus, structure, and, 'function,', but, their, study]), verbo([has]), complemento([been, complicated, by, both, their, large, size, and, their, complexity])]). relacion([sujeto(['Unexpectedly,', most, regions, of, 'GATA-1', and, 'NF-E2']), verbo([binding]), complemento([were, remote, from, gene, promoters, and, transcriptional, start, 'sites,', located, primarily, in, introns])]). relacion([sujeto(['Cooccupancy', with, 'FOG-1,', 'SCL,', and, 'MTA-2', was]), verbo([found]), complemento([at, all, regions, of, 'GATA-1', 'binding,', with, cooccupancy, of, 'SCL', and, 'MTA-2', also, found, at, regions, of, 'NF-E2', binding])]). relacion([sujeto(['Cooccupancy', of, 'GATA-1', and, 'NF-E2', was]), verbo([found]), complemento([frequently])]). relacion([sujeto(['A', common, signature, of, histone, 'H3', trimethylation, at, lysine, 4, ',', 'GATA-1,', 'NF-E2,', 'FOG-1,', 'SCL,', and, 'MTA-2']), verbo([binding]), complemento([and, consensus, 'GATA-1-E-box', binding, motifs, located, 34, to, 90, bp, away, from, 'NF-E2', binding, motifs, was, found, frequently, in, erythroid, 'cell-expressed', genes])]). relacion([sujeto(['These', results]), verbo([provide]), complemento([insights, into, our, understanding, of, membrane, protein, gene, regulation, in, erythropoiesis, and, the, regulation, of, complex, genetic, loci, in, erythroid, and, nonerythroid, cells, and, identify, numerous, candidate, regions, for, mutations, associated, with, 'membrane-linked', hemolytic, anemia])]). relacion([sujeto(['Two', 'GATA1-related', leukemias]), verbo([have]), complemento([been, 'described:', one, is, an, erythroleukemia, that, develops, in, mice, as, a, consequence, of, diminished, expression, of, 'wild-type', 'GATA1,', whereas, the, other, is, an, acute, megakaryoblastic, leukemia, '(', 'AMKL)', that, arises, in, 'Down', syndrome, children, as, a, consequence, of, somatic, 'N-terminal', truncation, '(', 'DeltaNT)', of, 'GATA1'])]). relacion([sujeto(['We', discovered, that, mice]), verbo([expressing]), complemento([the, shortened, 'GATA1', protein, '(', 'DeltaNTR', 'mice)', phenocopies, the, human, transient, myeloproliferative, disorder, '(', 'TMD)', that, precedes, 'AMKL', in, 'Down', syndrome, children])]). relacion([sujeto(['Previous', work]), verbo([has]), complemento([shown, that, 'FOG1', recruits, two, 'multi-protein', 'complexes,', the, nucleosome, remodeling, domain, '(', 'NuRD)', complex, and, a, 'C-terminal', binding, protein, '(', 'CTBP)-containing', 'complex,', into, association, with, 'GATA1', to, mediate, activation, and, repression, of, target, genes])]). relacion([sujeto(['To', elucidate, mechanisms, that, might, differentially]), verbo([regulate]), complemento([the, association, of, 'FOG1,', as, well, as, 'GATA1,', with, these, two, 'complexes,', we, characterized, a, previously, unrecognized, translational, isoform, of, 'FOG1'])]). relacion([sujeto(['We']), verbo([found]), complemento([that, an, 'N-terminally', truncated, version, of, 'FOG1', is, produced, from, an, internal, 'ATG', and, that, this, 'isoform,', designated, 'FOG1S,', lacks, the, nucleosome, remodeling, 'domain-binding', 'domain,', altering, the, complexes, with, which, it, interacts])]). relacion([sujeto(['Both', isoforms]), verbo([interact]), complemento([with, the, 'C-terminal', binding, protein, 'complex,', which, we, show, also, contains, 'lysine-specific', demethylase, 1, '(', 'LSD1)'])]). relacion([sujeto(['These', data]), verbo([reveal]), complemento([two, novel, mechanisms, for, the, regulation, of, 'GATA1', interaction, with, 'FOG1-dependent', protein, complexes, through, the, production, of, two, translational, isoforms, with, differential, interaction, profiles, and, independent, nuclear, localization, controls])]). relacion([sujeto(['Down', syndrome, '(', 'DS)', children]), verbo([have]), complemento([a, unique, genetic, susceptibility, to, develop, 'leukemia,', in, 'particular,', acute, megakaryocytic, leukemia, '(', 'AMkL)', associated, with, somatic, 'GATA1', mutations])]). relacion([sujeto(['The', study, of, this, genetic, susceptibility, with, the, use, of, 'DS', as, a, model, of, leukemogenesis]), verbo([has]), complemento([broad, applicability, to, the, understanding, of, leukemia, in, children, overall])]). relacion([sujeto(['This', mutational, spectrum, points, to, potential, oxidative, stress, and, aberrant, folate, metabolism, secondary, to, genes, on, chromosome, 21, '(', 'eg,', 'cystathionine-beta-synthase,', superoxide, 'dismutase)', as, potential]), verbo([causes]), complemento([of, 'GATA1', mutations])]). relacion([sujeto(['Furthermore,', 'DNA', repair, capacity, evaluated, in, 'DS', and, 'non-DS', patient, samples]), verbo([provided]), complemento([evidence, that, the, base, excision, repair, pathway, is, compromised, in, 'DS', 'tissues,', suggesting, that, inability, to, repair, 'DNA', damage, also, may, play, a, critical, role, in, the, unique, susceptibility, of, 'DS', children, to, develop, leukemia])]). relacion([sujeto(['Several', anticancer, drugs, with, diverse, chemical, structures, can]), verbo([induce]), complemento([differentiation, of, cancer, cells])]). relacion([sujeto(['Treatment', of, 'K562', cells, with, low, concentrations, of, the, tested, drugs]), verbo([activated]), complemento(['caspase-3', but, did, not, trigger, detectable, apoptosis])]). relacion([sujeto(['Instead,', elevated, levels, of, 'haemoglobin-positive', and, glycophorin, 'A/caspase-3-double-positive', cells, were, 'observed,']), verbo([suggesting]), complemento([involvement, of, 'caspase-3', in, 'drug-induced', differentiation])]). relacion([sujeto(['Inhibition', of, 'caspase-3', activity, significantly, reduced, the, ability, of, 'K562', cells, to]), verbo([execute]), complemento([the, differentiation, programme])]). relacion([sujeto(['Binding', activity, of, 'GATA-1,', transcription, factor, responsible, for, differentiation, and, cell, 'survival,', was, not, diminished, by]), verbo([increased]), complemento(['caspase-3', activity, during, 'drug-stimulated', differentiation])]). relacion([sujeto(['Our', results, could, explain, how, anticancer, 'drugs,', with, diverse, structures, and, modes, of, 'action,', can]), verbo([stimulate]), complemento([erythroid, differentiation, in, leukaemic, cells, with, appropriate, genetic, backgrounds])]). relacion([sujeto(['Our', findings, imply, that, some, similarities, exist, between, 'pharmacologically-induced', differentiation, of, erythroleukaemic, cells, and, normal, 'erythropoiesis,', both]), verbo([involving]), complemento(['caspase-3', activation, at, high, levels, of, 'anti-apoptotic', protein, 'Bcl-X(L)', and, chaperone, protein, 'Hsp70', '(', heat, shock, protein, 70, ')'])]). relacion([sujeto(['GATA-2', is, an, essential, transcription, factor, that]), verbo([regulates]), complemento([multiple, aspects, of, hematopoiesis])]). relacion([sujeto(['Here,', we, show, that, 'GATA-2', is]), verbo([required]), complemento([for, normal, megakaryocyte, development, as, well, as, aberrant, megakaryopoiesis, in, 'Gata1', mutant, cells])]). relacion([sujeto(['Genome-wide', microarray, analysis, and, chromatin, immunoprecipitation, studies, revealed, that, 'GATA-2']), verbo([regulates]), complemento([a, wide, set, of, 'genes,', including, cell, cycle, regulators, and, 'megakaryocyte-specific', genes])]). relacion([sujeto(['Surprisingly,', 'GATA-2', also, negatively]), verbo([regulates]), complemento([the, expression, of, crucial, myeloid, transcription, 'factors,', such, as, 'Sfpi1', and, 'Cebpa'])]). relacion([sujeto(['In', the, absence, of, 'GATA-1,', 'GATA-2']), verbo([prevents]), complemento([induction, of, a, latent, myeloid, gene, expression, program])]). relacion([sujeto(['Moreover,', our, data]), verbo([reveal]), complemento([that, overexpression, of, 'GATA-2', facilitates, aberrant, megakaryopoiesis])]). relacion([sujeto(['The', aim, of, the, present, study]), verbo([has]), complemento([been, to, establish, 'serum-free', culture, conditions, for, ex, vivo, expansion, and, differentiation, of, human, 'CD34(+)', cells, into, erythroid, lineage, and, to, study, the, chromatin, 'structure,', gene, 'expression,', and, transcription, factor, recruitment, at, the, 'alpha-globin', locus, in, the, developing, erythron])]). relacion([sujeto(['We', observe, distinct, patterns, of, the, histone, modifications, and, transcription, factor]), verbo([binding]), complemento([at, the, 'alpha-globin', locus, during, erythroid, differentiation, of, 'CD34(+)', cells])]). relacion([sujeto(['Nuclear', factor, 'erythroid-derived', 2, '(', 'NF-E2)', was, present, at, upstream, activator, sites, even, before, addition, of, erythropoietin, '(', 'EPO),', while]), verbo([bound]), complemento(['GATA-1', was, only, detectable, after, 'EPO', treatment])]). relacion([sujeto(['After', 7, days, of, 'EPO', 'treatment,', 'H3K4Me2', modification, uniformly]), verbo([increases]), complemento([throughout, the, 'alpha-globin', locus])]). relacion([sujeto(['Acetylation', at, 'H3K9', and]), verbo([binding]), complemento([of, 'Pol', 'II,', 'NF-E2,', and, 'GATA-1', were, restricted, to, certain, hypersensitive, sites, of, the, enhancer, and, theta, 'gene,', and, were, conspicuously, low, at, the, 'alpha-like', globin, promoters])]). relacion([sujeto(['Rearrangement', of, the, insulator]), verbo([binding]), complemento([factor, 'CTCF', took, place, at, and, around, the, 'alpha-globin', locus, as, 'CD34(+)', cells, differentiated, into, erythroid, pathway])]). relacion([sujeto(['Activation', of, 'alpha-globin', genes, upon, 'EPO', treatment]), verbo([involves]), complemento([initial, binding, of, 'Pol', 'II,', downregulation, of, 'pre-existing', factors, like, 'NF-E2,', removal, of, 'CTCF', from, the, 'locus,', then, rebinding, of, 'CTCF', in, an, altered, 'pattern,', and, concurrent, or, subsequent, binding, of, transcription, factors, like, 'GATA-1'])]). relacion([sujeto(['Hematopoiesis,', the, dynamic, process, of, blood, cell, 'development,', is]), verbo([regulated]), complemento([by, the, activity, of, the, bone, morphogenetic, protein, '(', 'BMP)', signaling, pathway, and, by, many, transcription, factors])]). relacion([sujeto(['However,', the, molecules, and, mechanisms, that]), verbo([regulate]), complemento(['BMP/Smad', signaling, in, hematopoiesis, are, largely, unknown])]). relacion([sujeto(['Here,', we, show, that, the, 'Integrator', 'complex,', an, evolutionarily]), verbo([conserved]), complemento([group, of, 'proteins,', functions, in, zebrafish, hematopoiesis, by, modulating, 'Smad/BMP', signaling])]). relacion([sujeto(['The', 'Integrator', complex, proteins, are, known, to, directly]), verbo([interact]), complemento([with, 'RNA', polymerase, 'II', to, mediate, 3, '\'', end, processing, of, 'U1', and, 'U2', snRNAs])]). relacion([sujeto(['We']), verbo([have]), complemento([identified, several, subunits, of, the, 'Integrator', complex, in, zebrafish])]). relacion([sujeto(['Antisense', 'morpholino-mediated', knockdown, of, the, 'Integrator', subunit, 5, '(', 'Ints5)', in, zebrafish, embryos, affects, 'U1', and, 'U2', snRNA, 'processing,']), verbo([leading]), complemento([to, aberrant, splicing, of, smad1, and, smad5, 'RNA,', and, reduced, expression, of, the, hematopoietic, genes, stem, cell, leukemia, '(', 'scl,', also, known, as, 'tal1)', and, gata1])]). relacion([sujeto(['Blood', smears, from, ints5, morphant, embryos, show]), verbo([arrested]), complemento([red, blood, cell, 'differentiation,', similar, to, 'scl-deficient', embryos])]). relacion([sujeto(['Interestingly,']), verbo([targeting]), complemento([other, 'Integrator', subunits, also, leads, to, defects, in, smad5, 'RNA', splicing, and, arrested, 'hematopoiesis,', suggesting, that, the, 'Ints', proteins, function, as, a, complex, to, regulate, the, 'BMP', pathway, during, hematopoiesis])]). relacion([sujeto(['Our', work, establishes, a, link, between, the, 'RNA', processing, machinery, and, the, downstream, effectors, of, 'BMP', 'signaling,', and]), verbo([reveals]), complemento([a, new, group, of, proteins, that, regulates, the, switch, from, primitive, hematopoietic, stem, cell, identity, and, blood, cell, differentiation, by, modulating, 'Smad', function])]). relacion([sujeto(['Children', with, 'Down', syndrome, '(', 'DS)']), verbo([have]), complemento([a, marked, increase, in, susceptibility, to, 'Acute', 'Megakaryoblastic', 'Leukaemia', '(', 'DS-AMKL)', and, the, closely, linked, neonatal, preleukaemic, 'syndrome,', 'Transient', 'Myeloproliferative', 'Disorder', '(', 'DS-TMD)'])]). relacion([sujeto(['The', distinct, stages, of, 'DS-TMD', and, 'DS-AMKL']), verbo([provide]), complemento([an, excellent, tractable, model, to, study, leukaemogenesis])]). relacion([sujeto(['The', findings, from, these, studies]), verbo([suggest]), complemento([that, mutations, in, the, key, haemopoietic, regulator, 'GATA1', '(', 'GATA', binding, protein, 1, ')', in, 'DS-AMKL', and, 'DS-TMD', may, be, useful, in, diagnosis, and, assessing, minimal, residual, disease])]). relacion([sujeto(['These', findings, raise, the, possibility, of, 'population-based', screening, strategies, for, 'DS-TMD', and, the, development, of, treatment, to, eliminate, the, preleukaemic, 'TMD', clone, to]), verbo([prevent]), complemento(['DS-AMKL'])]). relacion([sujeto(['These', findings]), verbo([have]), complemento([implications, for, leukaemia, biology, more, broadly, given, the, frequency, of, acquired, trisomy, in, other, human, leukaemias])]). relacion([sujeto(['In', our, 'report,', we]), verbo([have]), complemento([demonstrated, that, the, approximate, developmental, status, of, erythrocytes, and, the, progression, of, blood, formation, can, be, studied, 'non-invasively', in, 'GATA-1:DsRed', transgenic, zebrafish, '(', 'Danio', 'rerio)', embryo, and, larva, by, characterization, of, fluorescence, luminance, spectra])]). relacion([sujeto(['The', study, was, carried, out, for, animals]), verbo([maintained]), complemento([under, normoxic, and, hypoxic, '(', 152, and, 20, torr, 'PO(2)', 'respectively)', conditions, up, to, 10, days, 'post-fertilization', '(', 'dpf)', and, total, blood, cell, concentrations, and, fluorescent, 'cells\'', percentage, were, determined, for, this, purpose])]). relacion([sujeto(['The', luminescent, cells, with, medium, intensities, '(', 'IS3)', in, normoxic, animals, were]), verbo([found]), complemento([throughout, 2, to, 10, dpf, although, in, lower, quantity, while, in, hypoxic, group, they, appeared, from, 5, dpf, to, 10, dpf, showing, a, maximum, of, 15, '%', of, the, total, luminescent, cells, at, 8, dpf])]). relacion([sujeto(['The', total, blood, cell, concentration, dropped, after, 8, dpf, in, contrast, to, hypoxic, group, which, showed, further]), verbo([increasing]), complemento([trend])]). relacion([sujeto(['Rigorously', defined, reconstitution, assays, developed, in, recent, years]), verbo([have]), complemento([allowed, recognition, of, the, delicate, relationship, that, exists, between, hematopoietic, stem, cells, and, their, niches])]). relacion([sujeto(['This', balance]), verbo([ensures]), complemento([that, hematopoiesis, occurs, in, the, marrow, under, 'steady-state', conditions])]). relacion([sujeto(['By', analyzing, the, mechanism, that, rescues, hematopoiesis, in, mice, carrying, this, 'mutation,', we]), verbo([provide]), complemento([evidence, that, extramedullary, microenvironments, sustain, maturation, of, stem, cells, that, would, be, otherwise, incapable, of, maturing, in, the, marrow])]). relacion([sujeto(['AGGF1', is, an, angiogenic, 'factor,', and, its, deregulation, is]), verbo([associated]), complemento([with, a, vascular, malformation, consistent, with, 'Klippel-Trenaunay', syndrome, '(', 'KTS)'])]). relacion([sujeto(['Analyses', of, 5, '\'', -, and, 3, '\'', -, serial, promoter, deletions, defined, the, core, 'promoter/regulatory', 'elements,', including, two, repressor, sites, '(', from, -, 1971, to, -, 3990, and, from, -, 7521, to, -, 8391, ',', 'respectively)', and, two, activator, sites, '(', a, 'GATA1', consensus]), verbo([binding]), complemento([site, from, -, 295, to, -, 300, and, a, second, activator, site, from, -, 129, to, -, 159, ')'])]). relacion([sujeto(['A', similar, expression, profile, was]), verbo([found]), complemento([for, 'GATA1', and, 'AGGF1', in, cells, '(', including, various, endothelial, 'cells)', and, tissues])]). relacion([sujeto(['Electrophoretic', mobility, shift, assay, and, chromatin, immunoprecipitation, assays, demonstrated, that, 'GATA1', was, able, to]), verbo([bind]), complemento([to, the, 'AGGF1', 'DNA', in, vitro, and, in, vivo])]). relacion([sujeto(['Overexpression', of, 'GATA1']), verbo([increased]), complemento([expression, of, 'AGGF1'])]). relacion([sujeto(['We', identified, one, rare, polymorphism, -, 294, 'C>T', in, a, sporadic, 'KTS', 'patient,', which, is, located, in, the, 'GATA1', 'site,', disrupts]), verbo([binding]), complemento([of, 'GATA1', to, 'DNA,', and, abolishes, the, 'GATA1', stimulatory, effect, on, transcription, of, 'AGGF1'])]). relacion([sujeto(['These', results, demonstrate, that, 'GATA1']), verbo([regulates]), complemento([expression, of, 'AGGF1', and, reveal, a, novel, role, for, 'GATA1', in, endothelial, cell, biology, and, angiogenesis])]). relacion([sujeto(['Transient', myeloproliferative, disorder, '(', 'TMD)', is, a, hematologic, abnormality, usually]), verbo([associated]), complemento([with, 'Down', syndrome, that, may, present, with, a, skin, eruption, in, addition, to, typical, systemic, findings])]). relacion([sujeto(['We']), verbo([report]), complemento([a, case, of, a, patient, with, 'TMD', and, a, vesiculopustular, eruption, without, the, phenotypic, characteristics, of, 'Down', syndrome, who, was, found, to, have, mosaic, trisomy, 21])]). relacion([sujeto(['Mutations', of, the, globin, transcription, factor, 1, 'gene,', 'GATA1,', are]), verbo([associated]), complemento([with, both, 'TMD', and, acute, megakaryocytic, leukemia])]). relacion([sujeto(['The', tumor, antigen, 'PRAME', '(', preferentially]), verbo([expressed]), complemento([antigen, in, 'melanoma)', may, serve, as, a, marker, for, leukemic, transformation])]). relacion([sujeto(['We']), verbo([report]), complemento([an, illustrative, case, to, alert, clinicians, about, this, uncommon, cause, of, vesiculopustular, eruption, in, a, neonate, without, the, phenotypic, characteristics, of, 'Down', syndrome, and, review, the, clinical, findings, and, laboratory, studies, that, aid, in, accurate, diagnosis])]). relacion([sujeto(['HBS1L-MYB', intergenic, polymorphism, '(', 'HMIP)', on, chromosome, 6, q23, is]), verbo([associated]), complemento([with, elevated, fetal, hemoglobin, levels, and, has, pleiotropic, effects, on, several, hematologic, parameters])]). relacion([sujeto(['To', investigate, potential, regulatory, activity, in, the, 'region,', we]), verbo([have]), complemento([measured, sensitivity, of, the, sequences, to, 'DNase', 'I', cleavage, that, identified, 3, 'tissue-specific', 'DNase', 'I', hypersensitive, sites, in, the, core, intergenic, interval])]). relacion([sujeto(['We']), verbo([suggest]), complemento([that, 'HMIP', contains, regulatory, sequences, that, could, be, important, in, hematopoiesis, by, controlling, 'MYB', expression])]). relacion([sujeto(['This', study]), verbo([provides]), complemento([the, functional, link, between, genetic, association, of, 'HMIP', with, control, of, fetal, hemoglobin, and, other, hematologic, parameters])]). relacion([sujeto(['The', data]), verbo([suggest]), complemento([that, 'GATA-1', regulates, numerous, genes, of, various, functions, on, chromosome, 6, q])]). relacion([sujeto(['Here,', we, show, that, 'Gfi-1', transcription, is, positively]), verbo([regulated]), complemento([early, after, induction, of, erythroid, differentiation, and, remains, highly, active, to, late, erythroblasts])]). relacion([sujeto(['Using', chromatin, immunoprecipitation, assays, in, 'CD34+', cells, from, human, cord, 'blood,', we]), verbo([found]), complemento([that, 'Gfi-1', and, 'GATA-2', in, immature, progenitors, and, then, 'Gfi-1B', and, 'GATA-1', in, erythroblasts, are, bound, to, the, 'Gfi-1B', promoter, as, well, as, to, the, promoter, of, 'c-myc,', a, known, 'Gfi-1B', target, gene])]). relacion([sujeto(['Surprisingly,', this, 'Gfi-1/GATA-2-Gfi-1B/GATA-1', switch, observed, at, erythroblast, stages, is]), verbo([associated]), complemento([to, an, increase, in, the, 'Gfi-1B', transcription, whereas, it, triggers, repression, of, 'c-myc', transcription])]). relacion([sujeto(['Accordingly,', analysis, of, chromatin, modification, patterns, shows, that, 'HDAC,', 'CoREST,', and, 'LSD1', are]), verbo([recruited]), complemento([to, the, 'c-myc', promoter, leading, to, appearance, of, repressive, chromatin, marks])]). relacion([sujeto(['In', 'contrast,', the, 'Gfi-1B', promoter, remains]), verbo([associated]), complemento([with, a, transcriptionally, active, chromatin, configuration, as, highlighted, by, an, increase, in, histone, 'H3', acetylation, and, concomitant, release, of, the, 'LSD1', and, 'CoREST', corepressors])]). relacion([sujeto(['The', repressive, function, of, 'Gfi-1B', therefore, depends, on, the, nature, of, the, proteins]), verbo([recruited]), complemento([to, the, target, gene, promoters, and, on, chromatin, modifications])]). relacion([sujeto(['This', interaction]), verbo([requires]), complemento([a, 'LXCXE', motif, that, is, evolutionary, conserved, among, 'GATA-1', orthologs, yet, absent, from, the, other, 'GATA', family, members])]). relacion([sujeto(['A', 'GATA-1', mutant, unable, to]), verbo([bind]), complemento([pRb, fails, to, inhibit, cell, proliferation, and, results, in, mouse, embryonic, lethality, by, anemia])]). relacion([sujeto(['These', findings, clarify, the, previously, suspected, 'cell-autonomous', role, of, pRb, during, erythropoiesis, and, may]), verbo([provide]), complemento([a, unifying, molecular, mechanism, for, several, mouse, phenotypes, and, human, diseases, associated, with, 'GATA-1', mutations])]). relacion([sujeto(['Although', 'TAp73alpha', and, -, beta, proteins, are, capable, of]), verbo([inducing]), complemento([cell, cycle, 'arrest,', 'apoptosis,', and, 'differentiation,', 'DeltaNp73', acts, in, many, cell, types, as, a, 'dominant-negative', repressor, of, p53, and, 'TAp73'])]). relacion([sujeto(['It']), verbo([has]), complemento([been, proposed, that, p73, is, involved, in, myeloid, 'differentiation,', and, its, altered, expression, is, involved, in, leukemic, degeneration])]). relacion([sujeto(['However,', there, is, little, evidence, as, to, which, p73, variants, '(', 'TA', or, 'DeltaN)', are]), verbo([expressed]), complemento([during, differentiation, and, whether, specific, p73, isoforms, have, the, capacity, to, 'induce,', or, 'hinder,', this, differentiation, in, leukemia, cells])]). relacion([sujeto(['In', this, study, we, identify, 'GATA1', as, a, direct, transcriptional]), verbo([target]), complemento([of, 'TAp73alpha'])]). relacion([sujeto(['Furthermore,', 'TAp73alpha']), verbo([induces]), complemento(['GATA1', 'activity,', and, it, is, required, for, erythroid, differentiation])]). relacion([sujeto(['Moreover,', the, impaired, expression, of, 'GATA1', and, other, erythroid, genes, in, the, liver, of, p73KO, 'embryos,', together, with, the, moderated, anemia, observed, in, p73KO, young, 'mice,']), verbo([suggests]), complemento([a, physiological, role, for, 'TP73', in, erythropoiesis])]). relacion([sujeto(['In', this, 'study,', we]), verbo([have]), complemento([evaluated, the, dHPLC, screening, method, and, direct, sequencing, for, the, detection, of, 'GATA1', mutations, in, peripheral, blood, and, bone, marrow, aspirates, samples, from, children, with, 'Down', syndrome, '(', 'DS)'])]). relacion([sujeto(['Recently,', 'GATA-1,', a, key, transcription, factor]), verbo([involved]), complemento([in, hematopoietic, cell, 'development,', was, shown, to, directly, inhibit, 'STAT3', activity, in, vivo])]). relacion([sujeto(['Chromatin', immunoprecipitation, assay, was, used, to, ascertain, in, vivo, protein]), verbo([binding]), complemento([at, the, 'gamma-globin', 5, '\'', untranslated, region, '(', 5, '\'', 'UTR);', 'protein-protein', interactions, were, examined, by, coimmunoprecipitation, analysis])]). relacion([sujeto(['In', vitro, 'protein-DNA']), verbo([binding]), complemento([were, completed, using, surface, plasmon, resonance, and, electrophoretic, mobility, shift, assay])]). relacion([sujeto(['A', consensus, 'STAT3', 'DNA', probe]), verbo([inhibited]), complemento(['GATA-1-binding', in, a, 'concentration-dependent', 'manner,', and, the, converse, was, also, true])]). relacion([sujeto(['Enforced', 'STAT3', expression, augmented, its]), verbo([binding]), complemento([at, the, 'gamma-globin', 5, '\'', 'UTR', in, vivo, and, silenced, 'gamma-promoter-driven', luciferase, activity])]). relacion([sujeto(['These', data]), verbo([provide]), complemento([evidence, that, 'GATA-1', can, reverse, 'STAT3-mediated', 'gamma-globin', gene, silencing, in, erythroid, cells])]). relacion([sujeto(['It', was]), verbo([found]), complemento([that, total, and, reticulated, platelet, 'numbers,', plasma, thrombopoietin, '(', 'TPO)', concentration, and, the, mean, size, of, mature, megakaryocytes, were, circadian, but, not, entrained, by, food, intake])]). relacion([sujeto(['These', findings, imply, that, circadian, clock, gene, expression]), verbo([regulates]), complemento([platelet, turnover, in, mammals])]). relacion([sujeto(['A', subsequent, biochemical, study, of, the, 'MTC', cytoskeletal, proteins, using, polyacrylamide, gel, electrophoresis, and, western, blot, analysis, revealed, the, 'MTC', were, deficient, in, the, 'high-molecular', 'weight,', actin]), verbo([binding]), complemento(['protein,', talin])]). relacion([sujeto(['The', present, study]), verbo([has]), complemento([used, immunofluorescent, techniques, to, further, characterize, the, talin, deficiency])]). relacion([sujeto(['Results', confirm, that, the, 'GATA-1,', 'G208S', 'MTC', are, deficient, in, 'talin,', and, what, little, is, present, relocates, to, the, undersurface, of, the, plasma, membrane, following, activations, where, it]), verbo([associates]), complemento([with, adhesion, plaques])]). relacion([sujeto(['ARR19', '(', androgen, receptor, corepressor, of, 19, 'kDa),', which, encodes, for, a, 'leucine-rich', 'protein,', is]), verbo([expressed]), complemento([abundantly, in, the, testis])]). relacion([sujeto(['Further', analyses, revealed, that, 'ARR19', was]), verbo([expressed]), complemento([in, 'Leydig', 'cells,', and, its, expression, was, differentially, regulated, during, 'Leydig', cell, development])]). relacion([sujeto(['Adenovirus-mediated', overexpression, of, 'ARR19', in, 'Leydig', cells]), verbo([inhibited]), complemento([testicular, 'steroidogenesis,', 'down-regulating', the, expression, of, steroidogenic, 'enzymes,', which, suggests, that, 'ARR19', is, an, antisteroidogenic, factor])]). relacion([sujeto(['Interestingly,', 'cAMP/luteinizing', hormone, attenuated, 'ARR19', expression, in, a, fashion, similar, to, that, of, 'GATA-1,', which, was, previously]), verbo([reported]), complemento([to, be, 'down-regulated', by, cAMP])]). relacion([sujeto(['Sequence', analysis, of, the, 'Arr19', promoter, revealed, the, presence, of, two, putative, 'GATA-1']), verbo([binding]), complemento([motifs])]). relacion([sujeto(['Further', analyses, with, 5, '\'', deletion, and, point, mutants, of, putative, 'GATA-1']), verbo([binding]), complemento([motifs, showed, that, these, 'GATA-1', binding, sites, were, critical, for, high, promoter, activity])]). relacion([sujeto(['CREB-binding', protein, coactivated, 'GATA-1', and, markedly]), verbo([increased]), complemento([the, activity, of, the, 'Arr19', promoter])]). relacion([sujeto(['Altogether,', these, findings, demonstrate, that, 'ARR19', is, the]), verbo([target]), complemento([gene, of, 'GATA-1', and, suggest, that, 'ARR19', gene, expression, in, testicular, 'Leydig', cells, is, regulated, by, luteinizing, 'hormone/cAMP', signaling, via, the, control, of, 'GATA-1', 'expression,', resulting, in, the, control, of, testicular, steroidogenesis])]). relacion([sujeto(['We']), verbo([report]), complemento([a, male, infant, with, 'Down', syndrome, who, had, a, transient, myeloproliferative, disorder, associated, with, skin, lesions])]). relacion([sujeto(['On', 'PD', 10, ',', the, eruptions, resolved, spontaneously, and, the, population, of, blast, cells, in, peripheral, blood]), verbo([decreased]), complemento([to, 1, '%'])]). relacion([sujeto(['The', number, of, blast, cells, in, pustules]), verbo([decreased]), complemento([markedly, after, three, days])]). relacion([sujeto(['Chromatin', immunoprecipitation]), verbo([has]), complemento([been, widely, used, to, determine, the, status, of, histone, covalent, modifications, and, also, to, investigate, 'DNA-protein', and, 'protein-protein', associations, to, a, particular, genomic, location, in, vivo])]). relacion([sujeto(['Generally,', 'DNA', regulatory, elements, nucleate, the, interaction, of, several, transcription, factors, in, conjunction, with, ubiquitous, 'and/or', 'tissue-specific', cofactors, in, order, to]), verbo([regulate]), complemento([gene, transcription])]). relacion([sujeto(['Therefore,', it]), verbo([has]), complemento([become, relevant, to, determine, the, cohabitation, of, several, proteins, in, a, particular, developmental, stage, and, cell, type])]). relacion([sujeto(['Furthermore,', multiple, 'post-translational', histone, modifications, can, be, analyzed, on, the, same, genomic, location, with, the, aim, of, deciphering, the, combinatorial, pattern, of, histone, modifications]), verbo([associated]), complemento([to, specific, transcriptional, stages, during, cell, commitment])]). relacion([sujeto(['Here', we, describe, the, 'ChIP-reChIP', assay, that, represents, a, direct, strategy, to, determine, the, in, vivo, colocalization, of, proteins]), verbo([interacting]), complemento([or, in, close, contact, in, a, chromatinized, template, on, the, basis, of, double, and, independent, rounds, of, immunoprecipitations, with, 'high-quality', 'ChIP', grade, antibodies])]). relacion([sujeto(['In', 'cattle,', anaemia, is, the, key, feature, of, disease, and, persists, after, parasitaemia]), verbo([has]), complemento([declined, to, low, or, undetectable, 'levels,', but, treatment, to, clear, the, parasites, usually, resolves, the, anaemia])]). relacion([sujeto(['Furthermore,', functional, 'T', lymphocytes, are, not]), verbo([required]), complemento([for, the, induction, of, 'anaemia,', since, suppression, of, 'T', cell, activity, with, 'Cyclosporin', 'A', had, neither, an, effect, on, the, course, of, infection, nor, on, anaemia])]). relacion([sujeto(['Expression', of, genes]), verbo([involved]), complemento([in, erythropoiesis, and, iron, metabolism, was, followed, in, 'spleen,', liver, and, kidney, tissues, in, the, three, strains, of, mice, using, microarrays])]). relacion([sujeto(['However,', the, expression, of, transcription, factors, and, genes]), verbo([involved]), complemento([in, erythropoiesis, and, haemolysis, did, correlate, with, the, expression, of, the, inflammatory, cytokines, 'Il6', and, 'Ifng'])]). relacion([sujeto(['The', innate, immune, response, appears, to, be, the, major, contributor, to, the, inflammation]), verbo([associated]), complemento([with, anaemia, since, suppression, of, 'T', cells, with, 'CsA', had, no, observable, effect])]). relacion([sujeto(['Several', transcription, factors]), verbo([regulating]), complemento(['haematopoiesis,', 'Tal1,', 'Gata1,', 'Zfpm1', and, 'Klf1', were, expressed, at, consistently, lower, levels, in, 'C57BL/6', mice, suggesting, that, these, mice, have, a, lower, haematopoietic, capacity, and, therefore, less, ability, to, recover, from, haemolysis, induced, anaemia, after, infection])]). relacion([sujeto(['The', inclusion, of, chromatin, insulators, into, vectors]), verbo([has]), complemento([been, proposed, to, counteract, this, 'position-dependent', variegation, of, transgene, expression])]). relacion([sujeto(['Here,', we, show, that, the]), verbo([sea]), complemento([urchin, chromatin, 'insulator,', 'sns5,', protects, a, recombinant, 'gamma-retroviral', vector, from, the, negative, influence, of, chromatin, in, erythroid, milieu])]). relacion([sujeto(['This', element]), verbo([increases]), complemento([the, probability, of, vector, expression, at, different, chromosomal, integration, 'sites,', which, reduces, both, silencing, and, 'PEV'])]). relacion([sujeto(['By', chromatin, immunoprecipitation, '(', 'ChIP)', 'analysis,', we, demonstrated, the, specific]), verbo([binding]), complemento([of, 'GATA1', and, 'OCT1', transcription, factors, and, the, enrichment, of, hyperacetylated, nucleosomes, to, sns5, sequences])]). relacion([sujeto(['The', results]), verbo([suggest]), complemento([that, this, new, insulator, is, able, to, maintain, a, euchromatin, state, inside, the, provirus, locus, with, mechanisms, that, are, common, to, other, characterized, insulators])]). relacion([sujeto(['On', the, basis, of, its, ability, to, function, as, barrier, element, in, erythroid, milieu, and, to]), verbo([bind]), complemento([the, erythroid, specific, factor, 'GATA1,', the, inclusion, of, sns5, insulator, in, viral, vectors, may, be, of, practical, benefit, in, gene, transfer, applications, 'and,', in, 'particular,', for, gene, therapy, of, erythroid, disorders])]). relacion([sujeto(['One', such, signaling, pathway]), verbo([involves]), complemento(['RUNX1,', a, transcription, factor, upregulated, in, megakaryocytes, and, downregulated, in, erythroid, cells])]). relacion([sujeto(['The']), verbo([nuclear]), complemento([location, and, relocation, of, genes, play, crucial, regulatory, roles, in, gene, expression])]). relacion([sujeto(['SATB1,', a, 'MAR-binding', 'protein,']), verbo([has]), complemento([been, found, to, regulate, 'beta-like', globin, genes, through, chromatin, remodeling])]). relacion([sujeto(['In', this, 'study,', we, generated, 'K562', cells, 'over-expressing', 'wild-type', or]), verbo([nuclear]), complemento([matrix, targeting, sequences, '(', 'NMTS)-deficient', 'SATB1', and, found, that, like, 'wild-type', 'SATB1,', 'NMTS-deficient', 'SATB1', induces, out, loop, of, 'beta-globin', cluster, from, its, chromosome, territory, '(', 'CT),', while, it, is, unable, to, associate, the, cluster, with, the, nuclear, matrix, as, 'wild-type', 'SATB1', does, and, had, no, regulatory, functions, to, the, 'beta-globin', cluster])]). relacion([sujeto(['These', results, indicate, that, 'SATB1']), verbo([regulates]), complemento(['beta-like', globin, genes, at, the, nuclear, level, interlaced, with, chromatin, and, 'DNA', 'level,', and, emphasize, the, nuclear, matrix, binding, activity, of, 'SATB1', to, its, regulatory, function])]). relacion([sujeto([5, gene, knockdown, 'mice,', 'Gata1', expression, deteriorates, to, 5, '%', of, 'wild-type', allelic, 'expression,', a, level, insufficient, for, supporting, normal, erythropoiesis, and, one, that]), verbo([leads]), complemento([to, accumulation, of, erythroid, progenitors, that, are, readily, transformed, into, erythroblastic, leukemia])]). relacion([sujeto([5, 'leukemia,', which]), verbo([have]), complemento([a, potential, to, reestablish, leukemia, in, mice])]). relacion([sujeto(['In', 'cell-cycle', 'analyses,', 'LSP', cells, were, quiescent, like, 'HSCs,', but, reentry, into, the, cell, cycle, was]), verbo([stimulated]), complemento([by, 5, -, 'FU', treatment])]). relacion([sujeto(['Based', on, this, 'observation,', distinct, 'self-renewal', regulatory, mechanisms, in, 'LSCs', may, be, considered, as, one, of, the]), verbo([causes]), complemento([of, worsening, of, the, features, of, leukemia, after, injury, and, relapse])]). relacion([sujeto(['Tel', is, essential, for]), verbo([maintaining]), complemento([hematopoietic, stem, cells, in, the, bone, marrow])]). relacion([sujeto(['To', understand, the, role, of, 'TEL', in, 'erythropoiesis,', we, generated, transgenic, mice]), verbo([expressing]), complemento([human, 'TEL', under, the, control, of, 'Gata1', promoter, that, is, activated, during, the, course, of, the, 'erythroid-lineage', differentiation, '(', 'GATA1-TEL', transgenic, 'mice)'])]). relacion([sujeto(['In', transgenic, 'mice,']), verbo([enhanced]), complemento([expression, of, 'Alas-e', and, 'beta-major', globin, genes, was, observed, in, 'erythroid-committed', cells])]). relacion([sujeto(['When', embryonic, stem, cells]), verbo([expressing]), complemento([human, 'TEL', under, the, same, 'Gata1', promoter, were, differentiated, into, hematopoietic, 'cells,', immature, erythroid, precursor, increased, better, compared, to, controls, as, judged, from, the, numbers, of, 'burst-forming', unit, of, erythrocytes])]). relacion([sujeto(['Our', findings]), verbo([suggest]), complemento([some, roles, of, 'TEL', in, expanding, erythroid, precursors, and, accumulating, hemoglobin])]). relacion([sujeto(['The', transcription, factors, 'GATA-1', and, 'GATA-2']), verbo([have]), complemento([been, implicated, in, promoting, differentiation, of, eosinophilic, leukocytes])]). relacion([sujeto(['In', this, 'study,', we, examined, the, roles, of, 'GATA-1', and, 'GATA-2', in]), verbo([activating]), complemento([transcription, of, the, secretory, 'ribonuclease,', the, 'eosinophil-derived', neurotoxin, '(', 'EDN/RNase', 2, ')'])]). relacion([sujeto(['Antibody-augmented', electrophoretic, mobility, shift, and, chromatin, immunoprecipitation, analyses, indicate, that, 'GATA-1', and, 'GATA-2', proteins]), verbo([bind]), complemento([to, both, functional, 'GATA', consensus, sequences, in, the, 'EDN', promoter])]). relacion([sujeto(['Taken', 'together,', our, data]), verbo([suggest]), complemento([that, 'GATA-2', functions, directly, via, interactions, with, the, 'EDN', promoter, and, also, 'indirectly,', via, its, ability, to, regulate, the, expression, of, 'GATA-1', in, differentiating, eosinophils, and, eosinophil, cell, lines])]). relacion([sujeto(['We']), verbo([report]), complemento([a, 'sixteen-year-old', boy, with, 'Down', syndrome, and, relapse, of, 'AML', '(', 'M7),', who, has, been, in, complete, remission, '(', 'CR)', more, than, 12, months, after, bone, marrow, transplantation, '(', 'BMT)', from, an, 'HLA-matched', sibling, donor])]). relacion([sujeto(['Because', monosomy, 7, was, detected, at, onset, of, 'AML', and]), verbo([he]), complemento([experienced, relapse, after, the, treatment, of, 'AML', 99, 'Down', 'protocol,', his, prognosis, was, considered, very, poor])]). relacion([sujeto(['However,']), verbo([he]), complemento([achieved, 'CR', following, chemotherapy, that, included, 'high-dose', 'AraC', and, 'BMT', from, an, 'HLA-matched', sibling, donor, without, severe, complication])]). relacion([sujeto(['He']), verbo([has]), complemento([remained, in, 'CR', for, more, than, 12, months, after, 'BMT'])]). relacion([sujeto(['In', this, 'case,', 'GATA1', mutation, was, not, detected, at, either, onset, or, relapse, of, 'AML', and, it, is]), verbo([suggested]), complemento([that, this, case, is, in, a, different, risk, group, than, the, usual, 'Down', syndrome, patient, with, 'AML', showing, 'GATA1', mutation])]). relacion([sujeto(['Children', with, 'Down', syndrome, and, acute, megakaryoblastic, leukemia, '(', 'DS-AMKL)']), verbo([have]), complemento([been, shown, to, have, increased, sensitivity, to, cytarabine, based, chemotherapy])]). relacion([sujeto(['The', excellent, prognosis, in, patients, with, 'DS-AMKL', may, be, due, to, mutations, in, the, 'GATA1', gene]), verbo([leading]), complemento([to, reduced, expression, of, the, enzyme, cytidine, deaminase])]). relacion([sujeto(['This']), verbo([leads]), complemento([to, a, decreased, ability, to, convert, cytarabine, into, its, inactive, 'metabolite,', resulting, in, high, intracellular, concentration, of, this, cytotoxic, agent])]). relacion([sujeto(['We']), verbo([report]), complemento([two, cases, of, 'DS-AMKL', with, 'GATA1', mutations, who, had, poor, outcome])]). relacion([sujeto(['All-trans', retinoic, acid, '(', 'ATRA)']), verbo([induces]), complemento([granulocytic, maturation, of, 'WEHI-3B', 'D+', leukemia, cells, and, 'LiCl', enhances, this, 'maturation,', while, 'WEHI-3B', 'D-', cells, are, 'non-responsive', to, 'ATRA'])]). relacion([sujeto(['Transfection', of, 'SCL,']), verbo([expressed]), complemento([in, 'D-', but, absent, in, 'D+', 'cells,', into, 'D+', 'cells,', caused, resistance, to, 'ATRA,', while, transfection, of, 'GATA-1', into, 'D+', cells, produced, resistance, to, the, combination, of, 'ATRA', and, 'LiCl'])]). relacion([sujeto(['SCL', expression, in, 'D+', cells, did, not]), verbo([induce]), complemento([the, expression, of, 'c-Kit,', a, putative, target, gene, for, 'SCL'])]). relacion([sujeto(['LiCl,', known, to]), verbo([inhibit]), complemento([some, kinases, by, displacing, 'Mg2+,', did, not, affect, tyrosine, kinase, activity, of, the, cytoplasmic, domain, of, 'c-Kit'])]). relacion([sujeto(['The', hematopoietic, transcription, factor, 'GATA-1']), verbo([regulates]), complemento([the, expression, of, several, genes, associated, with, differentiation, of, erythroid, cells])]). relacion([sujeto(['We', show, here, the, inhibitory, effect, of, tumor, necrosis, factor, alpha, '(', 'TNFalpha),', a, proinflammatory, 'cytokine,', on, hemoglobinization, and, erythroid, transcription, factor, 'GATA-1', expression, in, erythroleukemia, '(', 'HEL)', as, well, as, in, chronic, myelogenous, leukemia, '(', 'K562)', 'cells,', which, were]), verbo([induced]), complemento([to, differentiate, towards, the, erythroid, lineage, after, aclacinomycin, '(', 'Acla),', doxorubicin, '(', 'Dox)', or, hemin, '(', 'HM)', treatment])]). relacion([sujeto(['As', a, 'result,', we, observed, 'i)', a]), verbo([decreased]), complemento([expression, of, 'Friend', of, 'GATA-1', '(', 'FOG-1),', an, essential, cofactor, of, 'GATA-1', transcription, 'factor,', 'ii)', a, downregulation, of, 'GATA-1', by, proteasomal, degradation, and, 'iii)', a, reduced, acetylation, level, of, 'GATA-1', in, 'HM-induced', 'K562', cells, after, 'TNF', treatment])]). relacion([sujeto(['As', a, 'result,', these, modifications, 'i)']), verbo([decreased]), complemento([the, level, of, 'GATA-1/FOG-1', 'complex,', 'ii)', unsettled, the, 'GATA-1/GATA-2', 'balance,', 'iii)', reduced, 'GATA-1', transcriptional, activity, and, 'iv)', inhibited, erythroid, marker, gene, expression, '(', glycophorin, 'A,', erythropoietin, 'receptor,', 'gamma-globin)', independently, of, the, cell, line, or, the, inducer, used])]). relacion([sujeto(['These', data]), verbo([provided]), complemento([new, insights, into, the, role, of, 'GATA-1', regulation, in, 'TNFalpha-mediated', inhibition, of, erythroid, differentiation, in, erythroleukemia])]). relacion([sujeto(['Although', oncogenic, functions, and, the, clinical, significance, of, 'Wilms', tumor, 1, '(', 'WT1)']), verbo([have]), complemento([been, extensively, studied, in, acute, 'leukemia,', the, regulatory, mechanism, of, its, transcription, still, remains, to, be, determined])]). relacion([sujeto(['We']), verbo([found]), complemento([a, significant, correlation, among, the, amounts, of, 'WT1,', 'GATA-1', and, 'GATA-2', mRNAs, from, leukemia, and, solid, tumor, cell, lines])]). relacion([sujeto(['Overexpression', and, small, interfering, 'RNA', '(', 'siRNA)', transfection, experiments, of, 'GATA-1', and, 'GATA-2', showed, that, these, 'GATA', transcription, factors, could]), verbo([induce]), complemento(['WT1', expression])]). relacion([sujeto(['The', 3, '\'', 'enhancer,', especially, the, distal, sites, out, of, six, putative, 'GATA']), verbo([binding]), complemento([sites, located, within, the, 'region,', but, not, the, intron, 3, 'enhancer,', were, essential, for, the, 'WT1', mRNA, level])]). relacion([sujeto(['Electrophoretic', mobility, shift, assay, '(', 'EMSA)', showed, both, 'GATA-1', and, 'GATA-2']), verbo([bound]), complemento([to, these, 'GATA', sites])]). relacion([sujeto(['Taken', 'together,', these, results]), verbo([suggest]), complemento([that, 'GATA-1', 'and/or', 'GATA-2', binding, to, a, 'GATA', site, of, the, 3, '\'', enhancer, of, 'WT1', played, an, important, role, in, 'WT1', gene, expression])]). relacion([sujeto(['TAM', receptors, '(', 'Tyro3,', 'Axl', and, 'Mer)', are]), verbo([expressed]), complemento([in, hematopoietic, tissues])]). relacion([sujeto(['We', investigated, the, role, of, 'TAM', receptors, in]), verbo([regulating]), complemento([erythropoiesis])]). relacion([sujeto(['Axl', and, 'Mer,', but, not, 'Tyro3,', were, constitutively]), verbo([expressed]), complemento([in, developing, erythroid, cells])]). relacion([sujeto(['We']), verbo([found]), complemento([an, inhibition, of, differentiation, at, the, transition, from, erythroid, progenitors, to, proerythroblasts, in, 'Axl(-/-)Mer(-/-)', mice])]). relacion([sujeto(['These', mice, exhibited, a, low, rate, of, erythropoietic, response, to, acute, anemia]), verbo([induced]), complemento([by, phenylhydrazine])]). relacion([sujeto(['Axl', and, 'Mer', play, an, important, role, in]), verbo([regulating]), complemento([erythropoiesis])]). relacion([sujeto(['This']), verbo([finding]), complemento([provides, a, novel, insight, into, the, mechanism, of, erythropoiesis])]). relacion([sujeto(['EVI1', is, an, oncogene, inappropriately]), verbo([expressed]), complemento([in, the, bone, marrow, '(', 'BM)', of, approximately, 10, '%', of, myelodysplastic, syndrome, '(', 'MDS)', patients])]). relacion([sujeto(['This', disease, is, characterized, by, severe, anemia, and, multilineage, myeloid, dysplasia, that, are, thought, to, be, a, major]), verbo([cause]), complemento([of, mortality, in, 'MDS', patients])]). relacion([sujeto(['We', earlier]), verbo([reported]), complemento([on, a, mouse, model, that, constitutive, expression, of, 'EVI1', in, the, 'BM', led, to, fatal, anemia, and, myeloid, 'dysplasia,', as, observed, in, 'MDS', 'patients,', and, we, subsequently, showed, that, 'EVI1', interaction, with, 'GATA1', blocks, proper, erythropoiesis])]). relacion([sujeto(['Whereas', this, interaction, could]), verbo([provide]), complemento([the, basis, for, the, erythroid, defects, in, 'EVI1-positive', 'MDS,', it, does, not, explain, the, alteration, of, myeloid, differentiation])]). relacion([sujeto(['Here,', we]), verbo([have]), complemento([examined, the, expression, of, several, genes, activated, during, terminal, myelopoiesis, in, 'BM', cells, and, identified, a, group, of, them, that, are, altered, by, 'EVI1'])]). relacion([sujeto(['We']), verbo([report]), complemento([here, that, 'EVI1', interacts, with, 'PU'])]). relacion([sujeto(['EVI1', does, not, seem, to]), verbo([inhibit]), complemento(['PU'])]). relacion([sujeto([1]), verbo([binding]), complemento([to, 'DNA,', but, rather, to, block, its, association, with, the, coactivator, 'c-Jun'])]). relacion([sujeto([1, -, 'EVI1', interaction, 'sites,', we, show, that, an, 'EVI1', point, 'mutant,', unable, to]), verbo([bind]), complemento(['PU'])]). relacion([sujeto([1, -]), verbo([regulated]), complemento([genes, and, allows, a, normal, differentiation, of, 'BM', progenitors, in, vitro])]). relacion([sujeto(['Chromatin', immunoprecipitation, '(', 'ChIP)', assays, coupled, to, genome, arrays, '(', 'Chip-on-chip)', or, massive, parallel, sequencing, '(', 'ChIP-seq)']), verbo([lead]), complemento([to, the, genome, wide, identification, of, binding, sites, of, chromatin, associated, proteins])]). relacion([sujeto(['Epitope', tags]), verbo([have]), complemento([often, been, used, as, more, reliable, alternatives])]). relacion([sujeto(['In', 'addition,', we]), verbo([have]), complemento([employed, protein, in, vivo, biotinylation, tagging, as, a, very, high, affinity, alternative, to, antibodies])]). relacion([sujeto(['In', this, paper, we, describe, the, optimization, of, biotinylation, tagging, for, 'ChIP', and, its, coupling, to, a, known, epitope, tag, in]), verbo([providing]), complemento([a, reliable, and, efficient, alternative, to, antibodies])]). relacion([sujeto(['We']), verbo([find]), complemento([that, the, omission, of, 'SDS', during, 'sonication,', the, use, of, fish, skin, gelatin, as, blocking, agent, and, choice, of, streptavidin, beads, can, lead, to, significantly, improved, 'ChIP', enrichments, and, lower, background, compared, to, antibodies])]). relacion([sujeto(['The', combined, use, of, the, very, high, affinity, biotin, tag, with, the, less, sensitive, to, crosslinking, 'V5', tag]), verbo([provides]), complemento([for, a, flexible, 'ChIP', platform, with, potential, implications, in, 'ChIP', sequencing, outcomes])]). relacion([sujeto(['The', conclusions]), verbo([have]), complemento([broader, implications, for, the, modelling, of, 'cell-fate', selection])]). relacion([sujeto(['This', study]), verbo([has]), complemento([used, the, same, technology, to, evaluate, macrothrombocytes, from, a, patient, with, the, 'GATA-1,', 'R216Q', mutation])]). relacion([sujeto(['The', dynamic, packaging, of, 'DNA', into, chromatin, is, a, fundamental, step, in, the, control, of, diverse]), verbo([nuclear]), complemento([processes])]). relacion([sujeto(['Whereas', certain, transcription, factors, and, chromosomal, components]), verbo([promote]), complemento([the, formation, of, 'higher-order', chromatin, 'loops,', the, 'co-regulator', machinery, mediating, loop, assembly, and, disassembly, is, unknown])]). relacion([sujeto(['Molecular', analysis, with, a, conditional, allele, of, 'GATA-1,', a, key, regulator, of, 'hematopoiesis,', in, a, novel, 'cell-based', system]), verbo([provided]), complemento([additional, evidence, that, 'BRG1', functions, early, in, chromatin, domain, activation, to, mediate, looping])]). relacion([sujeto(['Although', the, paradigm, in, which, chromatin, remodelers]), verbo([induce]), complemento([nucleosome, structural, transitions, is, well, 'established,', our, results, demonstrating, an, essential, role, of, 'BRG1', in, the, genesis, of, specific, chromatin, loops, expands, the, repertoire, of, their, functions])]). relacion([sujeto(['ETS2', and, 'ERG', are, transcription, 'factors,', encoded, on, human, chromosome, 21, '(', 'Hsa21),', that]), verbo([have]), complemento([been, implicated, in, human, cancer])]). relacion([sujeto(['DS-AMKL', blasts, harbor, a, mutation, in, 'GATA1,', which]), verbo([leads]), complemento([to, loss, of, 'full-length', protein, but, expression, of, the, 'GATA-1s', isoform])]). relacion([sujeto(['To', assess, the, consequences, of, 'ETS', protein, misexpression, on, 'megakaryopoiesis,', we]), verbo([expressed]), complemento(['ETS2,', 'ERG,', and, the, related, protein, 'FLI-1', in, 'wild-type', and, 'Gata1', mutant, murine, fetal, liver, progenitors])]). relacion([sujeto(['Although', overexpression, of, 'ETS', proteins]), verbo([increased]), complemento([the, proportion, of, 'CD41(+)', cells, generated, from, 'Gata1s-knockin', 'progenitors,', their, expression, led, to, a, significant, reduction, in, the, more, mature, 'CD42', fraction])]). relacion([sujeto(['These', findings]), verbo([provide]), complemento([evidence, for, synergy, between, alterations, in, 'GATA-1', and, overexpression, of, 'ETS', proteins, in, aberrant, megakaryopoiesis])]). relacion([sujeto(['We', develop, a, computational, model, for, the, hematopoietic, 'erythroid-myeloid', lineage, 'decision,', which, is, determined, by, a, genetic, switch]), verbo([involving]), complemento([the, genes, 'PU'])]). relacion([sujeto(['We', therefore]), verbo([suggest]), complemento([a, new, mechanism, involving, a, cofactor, that, is, regulated, as, well, as, recruited, by, one, of, the, master, genes, to, bind, to, the, antagonistic, partner, that, is, necessary, for, bistability, and, hence, 'switch-like', behavior])]). relacion([sujeto(['An', interesting, fallout, from, this, architecture, is, that, suppression, of, the, cofactor, through, external, means, can]), verbo([lead]), complemento([to, a, loss, of, 'cooperativity,', and, hence, to, a, primed, state, for, 'PU'])]). relacion([sujeto([1, -, 'GATA-1', switch, also]), verbo([interacts]), complemento([with, another, mutually, antagonistic, 'pair,', 'C/EBPalpha-FOG-1'])]). relacion([sujeto(['The', latter, pair, inherits, the, state, of, its, upstream, master, genes, and, further, reinforces, the, decision, due, to, several, feedback, 'loops,', thereby]), verbo([leading]), complemento([to, irreversible, commitment])]). relacion([sujeto(['The', genetic, 'switch,', which, handles, the, 'erythroid-myeloid', lineage, 'decision,', is, an, example, of, a, network, that, implements, both, a, primed, and, a, committed, state, by]), verbo([regulating]), complemento([cooperativity, through, recruitment, of, cofactors])]). relacion([sujeto(['Perturbing', the, feedback, between, the, master, regulators, and, downstream]), verbo([targets]), complemento([suggests, potential, reprogramming, strategies])]). relacion([sujeto(['Survivin1', '(', 'sur1)']), verbo([has]), complemento([been, shown, to, mediate, angiogenesis, but, not, hematopoiesis])]). relacion([sujeto([sur2, was]), verbo([expressed]), complemento([predominantly, in, the, intermediate, cell, mass, '(', 'ICM,', site, of, primitive, 'hematopoiesis)'])]). relacion([sujeto(['Morpholino', '(', 'MO)']), verbo([targeting]), complemento([at, 'intron1-exon2', junction, of, sur2, significantly, reduced, green, fluorescent, 'protein(+)', '(', 'erythroid)', cell, population, in, transgenic, 'Tg', '(', 'gata1:gfp)', embryos, at, 18, h, 'post-fertilization', '(', h])]). relacion([sujeto(['Molecular']), verbo([targeting]), complemento([was, confirmed, by, reverse, 'transcription-PCR', and, 'MO', specificity, by, successful, sur2, mRNA, rescue])]). relacion([sujeto([sur2, 'MO', also, downregulated, genes]), verbo([associated]), complemento([with, hematopoietic, stem, cells, '(', 'scl,', 'lmo2),', erythroid, '(', 'gata1,', 'alpha-', and, 'beta-embryonic', 'hemoglobins)', as, well, as, early, '(', pu])]). relacion([sujeto(['This', was]), verbo([associated]), complemento([with, an, increase, in, apoptosis, in, the, 'ICM', and, alteration, of, 'cell-cycle', status, of, erythroid, cells])]). relacion([sujeto(['In', 'conclusion,', sur2, is, important, in]), verbo([maintaining]), complemento([hematopoietic, stem, and, lineage, committed, cells, during, zebrafish, 'development,', by, virtue, of, its, antiapoptotic, activity, in, a, caspase, dependent, and, cell, autonomous, fashion])]). relacion([sujeto(['Moreover,', hematologists]), verbo([have]), complemento([also, noted, that, these, children, commonly, show, 'macrocytosis,', abnormal, platelet, 'counts,', and, an, increased, incidence, of, transient, myeloproliferative, disease, '(', 'TMD),', acute, megakaryocytic, leukemia, '(', 'AMKL),', and, acute, lymphoid, leukemia, '(', 'ALL)'])]). relacion([sujeto(['In', this, 'review,', we, summarize, the, clinical, manifestations, and, characteristics, of, these, 'leukemias,']), verbo([provide]), complemento([an, update, on, therapeutic, strategies, and, patient, 'outcomes,', and, discuss, the, most, recent, advances, in, 'DS-leukemia', research])]). relacion([sujeto(['With', the]), verbo([increased]), complemento([knowledge, of, the, way, in, which, trisomy, 21, affects, hematopoiesis, and, the, specific, genetic, mutations, that, are, found, in, 'DS-associated', 'leukemias,', we, are, well, on, our, way, toward, designing, improved, strategies, for, treating, both, myeloid, and, lymphoid, malignancies, in, this, 'high-risk', population])]). relacion([sujeto(['Somatic', 'CD34+', hematopoietic, 'stem/precursor', cells, '(', 'HSPCs)', give, rise, to, hematopoietic, cells, and, endothelial, cells, and]), verbo([have]), complemento([been, used, in, clinical, applications])]). relacion([sujeto(['Understanding', the, genes, responsible, for, stemness, and, how, they]), verbo([interact]), complemento([with, each, other, will, help, us, to, manipulate, these, cells, more, efficiently, in, the, future])]). relacion([sujeto(['Systems', biology, and, advanced, bioinformatics, tools, were, used, to, help, clarify, the, genetic, networks]), verbo([associated]), complemento([with, these, stem, cell, genes])]). relacion([sujeto(['We', identified, 'CD34+', 'HSPC', genes, and]), verbo([found]), complemento([that, they, were, involved, in, critical, biologic, processes, such, as, cell, cycle, 'regulation,', chromosome, 'organization,', and, 'DNA', repair])]). relacion([sujeto(['Analysis', of, 'HSPC-enriched', genes, using, systems, biology, tools, revealed, a, complex, genetic, network, functioning, in, 'CD34+', 'cells,', in, which, several, genes]), verbo([acted]), complemento([as, hubs, to, maintain, the, stability, '(', such, as, 'GATA1)', or, connectivity, '(', such, as, hepatic, growth, 'factor)', of, the, whole, network])]). relacion([sujeto(['This', study]), verbo([provides]), complemento([the, foundation, for, a, more, detailed, understanding, of, 'CD34+', 'HSPCs'])]). relacion([sujeto(['Although', acquired, mutations, in, the, 'GATA1', gene]), verbo([have]), complemento([been, reported, for, 'Down', 'syndrome-related', acute, megakaryoblastic, leukemia, '(', 'DS-AMKL)', in, 'Caucasians,', this, is, the, first, report, of, a, 'Korean', 'Down', syndrome, patient, with, 'AMKL', carrying, a, novel, mutation, of, the, 'GATA1', gene])]). relacion([sujeto(['This', mutation]), verbo([caused]), complemento([a, premature, termination, at, codon, 67, and, expression, of, an, abnormal, 'GATA-1', protein, with, a, defective, 'N-terminal', activation, 'domain,', and, the, absence, of, 'full-length', 'GATA-1', protein])]). relacion([sujeto(['An']), verbo([increased]), complemento([cell, 'death,', together, with, decreased, cell, 'proliferation,', decreased, expression, of, 'erythroid-specific', genes, including, 'GATA1,', and, a, delay, in, fetal, to, adult, globin, switching, were, observed])]). relacion([sujeto(['At', the, same, 'time,', myeloid, differentiation, was, slightly, favoured, thus]), verbo([suggesting]), complemento([that, 'Ikaros', could, be, involved, in, the, control, of, the, 'myeloid/erythroid', commitment])]). relacion([sujeto(['During', development, and, 'erythropoiesis,', globin, gene, expression, is, finely]), verbo([modulated]), complemento([through, an, important, network, of, transcription, factors, and, chromatin, modifying, activities])]). relacion([sujeto(['In', this]), verbo([report]), complemento([we, provide, in, vivo, evidence, that, endogenous, 'Ikaros', is, recruited, to, the, human, 'beta-globin', locus, and, targets, the, histone, deacetylase, 'HDAC1', and, the, chromatin, remodeling, protein, 'Mi-2', to, the, human, 'gamma-gene', 'promoters,', thereby, contributing, to, 'gamma-globin', gene, silencing, at, the, time, of, the, 'gamma-', to, 'beta-globin', gene, transcriptional, switch])]). relacion([sujeto(['We', show, for, the, first, time, that, 'Ikaros']), verbo([interacts]), complemento([with, 'GATA-1', and, enhances, the, binding, of, the, latter, to, different, regulatory, regions, across, the, locus])]). relacion([sujeto(['The', expression, of, 'FGF1', was, firstly]), verbo([found]), complemento([in, visceral, mesoderm, around, periphery, of, yolk, sac, blood, island, at, day, 16, ',', while, was, little, inside, it])]). relacion([sujeto(['KDR', was, not, or, lowly]), verbo([expressed]), complemento([and, 'CD34', and, 'CD133', were, not, expressed, then])]). relacion([sujeto(['The', expression, 'increased,', gray, value]), verbo([decreased]), complemento([and, staining, enhanced, at, day, 21])]). relacion([sujeto(['Strong', staining, of, 'CD34+,', 'CD133+', and, 'KDR+', cells, were]), verbo([found]), complemento([in, blood, island, and, mesoderm, at, day, 30, ',', their, gray, values, changed, from, 156, +, /, -, 16, ',', 173, +, /, -, 18, and, 160, +, /, -, 14, to, 53, +, /, -, 7, ',', 52, +, /, -, 6, and, 69, +, /, -, 8, respectively])]). relacion([sujeto(['Moderate', expression, of, 'CD34+,', 'CD133+,', 'KDR+', cells]), verbo([increased]), complemento([at, day, 45, ',', the, cells, aggregated, into, mass, in, blood, island, and, 'FGF1+', cells, did, the, same, in, blood, 'island,', while, little, in, mesoderm])]). relacion([sujeto(['After', 7, 'weeks,', 'CD133+,', 'KDR+,', 'CD34+', cells, significantly]), verbo([decreased]), complemento([their, gray, values, 'increased,', the, staining, became, week])]). relacion([sujeto(['FGF1', was, weakly]), verbo([expressed]), complemento([in, yolk, sac, and, its, gray, value, increased, to, 179, +, /, -, 22])]). relacion([sujeto(['RT-PCR', showed, 'Ihh,', 'SCL,', 'GATA-1', and, 'GATA-2', were]), verbo([expressed]), complemento([at, different, time, in, yolk, sac])]). relacion([sujeto([1, were, not]), verbo([expressed]), complemento([at, day, 16, ',', and, then, expressed])]). relacion([sujeto(['The', 'FGF', pathway]), verbo([regulates]), complemento([primitive, hematopoiesis, by, modulating, transcription, factors, such, as, 'Gata1', expression, level, and, activity])]). relacion([sujeto(['To']), verbo([gain]), complemento([insight, into, the, mechanisms, responsible, for, these, 'abnormalities,', we, analyzed, the, hematopoietic, development, of, the, 'Ts1Cje', mouse, model, of, 'DS'])]). relacion([sujeto(['Despite', these, 'defects,', the, 'Ts1Cje', mice, do, not, develop, disease, resembling, either, 'TMD', or, 'AMKL,', and, this, was, not, altered, by, a]), verbo([loss]), complemento([of, function, allele, of, 'Gata1'])]). relacion([sujeto(['Thus,']), verbo([loss]), complemento([of, 'Gata1', and, partial, trisomy, of, chromosome, 21, 'orthologs,', when, 'combined,', do, not, appear, to, be, sufficient, to, induce, 'TMD', or, 'AMKL-like', phenotypes, in, mice])]). relacion([sujeto(['To', examine, how, 'Gata1', gene, expression, is]), verbo([regulated]), complemento([in, a, 'stage-specific', 'manner,', transgenic, mouse, lines, expressing, green, fluorescent, protein, '(', 'GFP)', reporter, from, the, 'Gata1', locus, in, a, bacterial, artificial, chromosome, '(', 'G1BAC-GFP)', were, prepared])]). relacion([sujeto(['We']), verbo([found]), complemento([that, the, 'GFP', reporter, expression, faithfully, recapitulated, 'Gata1', gene, expression])]). relacion([sujeto(['We', examined, the, functions, of, the, 'Gata1', gene, hematopoietic, enhancer, '(', 'G1HE)', and, the, highly]), verbo([conserved]), complemento(['GATA', box, in, the, enhancer, core])]). relacion([sujeto(['Both', deletion, of, the, 'G1HE', and, substitution, mutation, of, the, 'GATA', box]), verbo([caused]), complemento([almost, complete, loss, of, 'GFP', expression, in, the, 'BREP', 'fraction,', but, the, 'CREP', stage, expression, was, suppressed, only, 'partially,', indicating, the, critical, contribution, of, the, 'GATA', box, to, the, 'BREP', stage, expression, of, 'Gata1'])]). relacion([sujeto(['Consistently,']), verbo([targeted]), complemento([deletion, of, 'G1HE', from, the, chromosomal, 'Gata1', locus, provoked, suppressed, expression, of, the, 'Gata1', gene, in, the, 'BREP', 'fraction,', which, led, to, aberrant, accumulation, of, 'BREP', stage, hematopoietic, progenitor, cells])]). relacion([sujeto(['Gata-1', overexpression, was, related, to, advanced, age, and, a, low, percentage, of, bone, marrow, blasts, and, was]), verbo([associated]), complemento([with, the, expression, of, 'CD34', antigen, and, lymphoid, 'T', markers])]). relacion([sujeto(['The', negative, impact, of, 'Gata-1', expression, on, the, probability, of, achieving, complete, remission]), verbo([has]), complemento([been, confirmed])]). relacion([sujeto(['Gata-2', overexpression, was]), verbo([associated]), complemento([with, a, low, percentage, of, blasts, in, 'BM', and, males])]). relacion([sujeto(['Expression', of, 'c-MPL', was]), verbo([associated]), complemento([with, 'CD34+', 'AML', and, 'M2', 'FAB', 'AML', subtype])]). relacion([sujeto(['A', higher, expression, of, 'EKLF', was]), verbo([found]), complemento([in, secondary, 'AML', versus, primary, 'AML'])]). relacion([sujeto(['Nevertheless,', patients]), verbo([expressing]), complemento(['EKLF', had, a, longer, overall, survival, and, event, free, survival, than, those, patients, that, did, not, express, 'EKLF'])]). relacion([sujeto(['Our', study]), verbo([has]), complemento([identified, expression, of, 'EKLF', as, a, factor, with, a, favorable, impact, on, prognosis, in, 'AML'])]). relacion([sujeto(['New', drugs, and, strategies, aimed, at]), verbo([preventing]), complemento([infections, could, further, improve, the, outcome, of, 'APS', and, other, autoimmune, diseases])]). relacion([sujeto(['A', 'Brazilian', network, integrating, hospitals, and, scientific, institutions, from, all, country, regions]), verbo([has]), complemento([been, established])]). relacion([sujeto(['The', unique, characteristics, of, the, 'Brazilian', population, combined, with, a, large, clinical, and, epidemiologic, framework, for, patient, ascertainment]), verbo([has]), complemento([enabled, 'large-scale', epidemiological, studies, on, childhood, leukemia, in, 'Brazil'])]). relacion([sujeto(['Genetic', association, studies]), verbo([have]), complemento([identified, sequence, variants, in, the, gene, 'BCL11A', that, influence, 'HbF', levels])]). relacion([sujeto(['The', 'high-HbF', 'BCL11A', genotype, is]), verbo([associated]), complemento([with, reduced, 'BCL11A', expression])]). relacion([sujeto(['Down-regulation', of, 'BCL11A', expression, in, primary, adult, erythroid, cells]), verbo([leads]), complemento([to, robust, 'HbF', expression])]). relacion([sujeto(['Consistent', with, a, direct, role, of, 'BCL11A', in, globin, gene, 'regulation,', we]), verbo([find]), complemento([that, 'BCL11A', occupies, several, discrete, sites, in, the, 'beta-globin', gene, cluster])]). relacion([sujeto(['BCL11A', emerges, as, a, therapeutic]), verbo([target]), complemento([for, reactivation, of, 'HbF', in, 'beta-hemoglobin', disorders])]). relacion([sujeto(['Mechanisms', explaining, the, cellular, basis, for, 'D6', function]), verbo([have]), complemento([been, based, on, 'D6', expression, by, lymphatic, endothelial, cells])]). relacion([sujeto(['In', this, 'study,', we, demonstrate, that, functional, 'D6', is, also]), verbo([expressed]), complemento([by, murine, and, human, hemopoietic, cells, and, that, this, expression, can, be, regulated, by, 'pro-', and, 'anti-inflammatory', agents])]). relacion([sujeto(['We', propose, a, model, for, 'D6', function, in, which, 'leukocytes,', within, inflamed, 'sites,']), verbo([activate]), complemento(['D6', expression, and, thus, trigger, resolution, of, inflammatory, responses])]). relacion([sujeto(['Our', data, on, 'D6', expression, by, circulating, 'DCs', and, 'B', cells, also]), verbo([suggest]), complemento([alternative, roles, for, 'D6,', perhaps, in, the, coordination, of, innate, and, adaptive, immune, responses])]). relacion([sujeto(['These', data, therefore, alter, our, models, of, in, vivo, 'D6', function, and]), verbo([suggest]), complemento([possible, 'discrete,', and, 'novel,', roles, for, 'D6', on, lymphatic, endothelial, cells, and, leukocytes])]). relacion([sujeto(['GATA-1', controls, hematopoietic, development, by]), verbo([activating]), complemento([and, repressing, gene, 'transcription,', yet, the, in, vivo, mechanisms, that, specify, these, opposite, activities, are, unknown])]). relacion([sujeto(['By', examining, the, composition, of, 'GATA-1-associated', protein, complexes, in, a, conditional, erythroid, rescue, system, as, well, as, through, the, use, of, tiling, arrays, we, detected, the, 'SCL/TAL1,', 'LMO2,', 'Ldb1,', 'E2A', complex, at, all, positively]), verbo([acting]), complemento(['GATA-1-bound', elements, examined])]). relacion([sujeto(['Similarly,', the, 'SCL', complex, is, present, at, all]), verbo([activating]), complemento(['GATA', elements, in, megakaryocytes, and, mast, cells])]). relacion([sujeto(['A', 'DNA-binding', defective, form, of, 'SCL']), verbo([maintains]), complemento([association, with, a, subset, of, active, 'GATA', elements, indicating, that, 'GATA-1', is, a, key, determinant, for, 'SCL', recruitment])]). relacion([sujeto(['An', 'X-linked', mutation, in, the, 'GATA-1', transcription, 'factor,', 'G208S,']), verbo([causes]), complemento([macrothrombocytopenia, and, serious, bleeding, problems, in, affected, male, family, members])]). relacion([sujeto(['The', present, investigation]), verbo([has]), complemento([evaluated, the, cytoskeletal, proteins, of, the, 'GATA-1,', 'G208S', macrothrombocytes, of, two, male, patients, by, page, gel, electrophoresis, and, 'Western', blot, analysis])]). relacion([sujeto(['Functions', for, this, pathway, in, adult, hematopoiesis]), verbo([have]), complemento([been, challenging, to, probe, in, other, models])]). relacion([sujeto(['Third,', we, generated, a, transgenic, line, that]), verbo([targets]), complemento([the, expression, of, a, 'dominant-negative', 'BMP', receptor, to, 'adult-stage', 'Gata1+', progenitor, cells])]). relacion([sujeto(['Adult', fish, with, a, strong, mutant, smad5, allele, are, anemic, at, steady, state, 'and,', in, 'addition,']), verbo([respond]), complemento([to, hemolytic, anemia, with, kinetics, that, are, altered, compared, to, 'wild-type', fish])]). relacion([sujeto(['Fish']), verbo([expressing]), complemento([a, mutant, 'BMP', receptor, in, early, 'Gata1+', definitive, progenitors, generate, excessive, eosinophils])]). relacion([sujeto(['Our', study]), verbo([provides]), complemento([proof, of, principle, that, regulation, of, adult, hematopoiesis, can, be, studied, in, zebrafish, by, altering, specific, pathways])]). relacion([sujeto(['We', show, that, the, 'BMP', signaling, pathway, is, relevant, for, adult, hematopoiesis, to]), verbo([maintain]), complemento([steady, state, 'erythropoiesis,', control, the, erythropoietic, response, following, stress, 'anemia,', and, to, generate, normal, numbers, of, eosinophils])]). relacion([sujeto(['The', results, showed, that, this, complex, prescription]), verbo([increased]), complemento([the, 'gamma-globin,', 'EpoR,', 'Spi', and, 'FKLF', expression, and, decreased, the, 'Ckit,', 'GATA1', and, 'GATA2', expression])]). relacion([sujeto(['Even', 'that,', this, study, results, indicated, that, the, 'YiSui', 'ShenXu', 'Granule']), verbo([has]), complemento([its, molecular, pharmacological, basis, in, treating, 'beta-thalassemia'])]). relacion([sujeto(['Enhanced', differentiation, of, human, embryonic, stem, cells, '(', 'HESCs),']), verbo([induced]), complemento([by, genetic, modification, could, potentially, generate, a, vast, number, of, diverse, cell, types])]). relacion([sujeto(['Such', genetic, modifications]), verbo([have]), complemento([frequently, been, achieved, by, 'over-expression', of, individual, regulatory, proteins])]). relacion([sujeto(['However,', careful, evaluation, of, the, expression, levels, is, 'critical,', since, this, might]), verbo([have]), complemento([important, implications, for, the, differentiation, potential, of, 'HESCs'])]). relacion([sujeto(['To', 'date,', attempts, to]), verbo([promote]), complemento([osteogenesis, by, means, of, gene, transfer, into, 'HESCs', using, the, early, bone, &, 'quot;master"', transcription, factor, osterix, '(', 'Osx)', have, not, been, reported])]). relacion([sujeto(['In', this, 'study,', we, attained, 'HESC', subpopulations]), verbo([expressing]), complemento([two, significantly, different, levels, of, 'Osx,', following, lentiviral, gene, transfer])]). relacion([sujeto(['Both', subpopulations, exhibited, spontaneous, differentiation, and, reduced, expression, of, markers, characteristic, of, the, pluripotent, 'phenotype,', such, as, 'SSEA3,', 'Tra1-60,', and, 'Nanog,', 'In', order, to]), verbo([promote]), complemento([bone, 'differentiation,', the, cells, were, treated, with, ascorbic, 'acid,', 'beta-glycerophosphate', and, dexamethasone])]). relacion([sujeto(['The', high, level, of, 'Osx,', compared, to, endogenous, levels]), verbo([found]), complemento([in, primary, human, 'osteoblasts,', did, not, enhance, osteogenic, 'differentiation,', and, did, not, 'up-regulate', collagen, 'I', expression])]). relacion([sujeto(['We', show, that, the, high, 'Osx', levels, instead]), verbo([induced]), complemento([the, commitment, towards, the, 'hematopoietic-endothelial', 'lineage-by', 'up-regulating', the, expression, of, 'CD34', and, 'Gata1'])]). relacion([sujeto(['Conversely,', forced, high, level, expression, of, the, homeobox, transcription, factor, 'HoxB4,', a, known, regulator, for, early, 'hematopoiesis,']), verbo([promoted]), complemento([osteogenesis, in, 'HESCs,', while, low, levels, of, 'HoxB4', lead, to, hematopoietic, gene, expression])]). relacion([sujeto(['In', the, past, few, 'decades,', the, crucial, role, of, 'GATA-1', in, normal, human, hematopoiesis]), verbo([has]), complemento([been, delineated])]). relacion([sujeto(['As', would, be, 'expected,', mutations, in, 'GATA-1']), verbo([have]), complemento([subsequently, been, found, to, have, important, clinical, 'significance,', and, are, directly, linked, to, deregulated, formation, of, certain, blood, cell, lineages])]). relacion([sujeto(['These', five, human, diseases, 'are:', 'X-linked', thrombocytopenia, '(', 'XLT),', 'X-linked', thrombocytopenia, with, thalassemia, '(', 'XLTT),', congenital, erythropoietic, porphyria, '(', 'CEP),', transient, myeloproliferative, disorder, '(', 'TMD)', and, acute, megarakaryoblastic, leukemia, '(', 'AMKL)']), verbo([associated]), complemento([with, 'Trisomy', 21, ',', 'and,', 'lastly,', a, particular, subtype, of, anemia, associated, with, the, production, of, 'GATA-1s,', a, 'shortened,', mutant, isoform, of, the, 'wild-type', 'GATA-1'])]). relacion([sujeto(['The', different, phenotypic, expressions]), verbo([associated]), complemento([with, 'GATA-1', mutations, illustrate, the, integral, function, of, the, transcription, factor, in, overall, body, homeostasis])]). relacion([sujeto(['Furthermore,', these, direct, 'genotype-phenotype', correlations, reinforce, the, importance, of, unraveling, the, human, 'genome,', as, such, connections, may]), verbo([lead]), complemento([to, important, therapeutic, or, preventive, therapies])]). relacion([sujeto(['Children', with, 'Down', syndrome, '(', 'DS)']), verbo([have]), complemento([a, greatly, increased, risk, of, acute, megakaryoblastic, leukemia, '(', 'AMKL)', and, acute, lymphoblastic, leukemia, '(', 'ALL)'])]). relacion([sujeto(['Both', 'DS-AMKL', and, the, related, transient, myeloproliferative, disorder, '(', 'TMD)']), verbo([have]), complemento(['GATA1', mutations, as, 'obligatory,', early, events])]). relacion([sujeto(['These', results, infer, a, complex, molecular, pathogenesis, for, 'DS-ALL', 'leukemogenesis,', with, trisomy, 21, as, an, initiating, or, first, hit, and, with, chromosome, 'aneuploidy,', gene, 'deletions,', and]), verbo([activating]), complemento(['JAK2', mutations, as, complementary, genetic, events])]). relacion([sujeto(['Furthermore,', our, data]), verbo([suggest]), complemento([that, one, main, source, of, definitive, erythropoietic, cells, is, the, 'pre-existing', vascular, endothelial, cells])]). relacion([sujeto(['Maltose']), verbo([binding]), complemento([protein, '(', 'MBP)', pull, down, and, mammalian, 'two-hybrid', assay, '(', 'MTHA)', were, used, to, identify, the, interaction, partners, of, 'LMO2-C', in, 'K562', cells])]). relacion([sujeto(['MBP-LMO2-C', fusion, protein, was]), verbo([expressed]), complemento([and, purified, in, soluble, form, successfully])]). relacion([sujeto(['Endogenous', 'GATA1', and, 'LDB1', proteins, were, confirmed, to]), verbo([bind]), complemento([to, 'LMO2-C', by, 'MBP', pull, down, analysis])]). relacion([sujeto(['The', 'MTHA', also, showed, that, 'LMO2-C', had, comparable]), verbo([binding]), complemento([affinities, to, 'LDB1', with, 'LMO2-L,', and, over, expression, of, 'LMO2-C', prevented, 'LMO2-L', from, binding, to, 'LDB1,', the, inhibition, rate, being, '(', 81.13, +, /, -, 0.68, ')', '%'])]). relacion([sujeto(['LMO2-C', can]), verbo([bind]), complemento([endogenous, 'GATA1', and, 'LDB1', protein, in, 'K562', cells, and, down, regulates, the, expression, of, 'GPA'])]). relacion([sujeto(['Transient', leukemia, '(', 'TL)']), verbo([has]), complemento([been, observed, in, approximately, 10, '%', of, newborn, infants, with, 'Down', syndrome, '(', 'DS)'])]). relacion([sujeto(['Stem', cell, factor, '(', 'SCF)']), verbo([stimulated]), complemento([the, proliferation, of, the, 'TL', cells, from, five, patients, and, treatment, with, the, tyrosine, kinase, inhibitor, imatinib, suppressed, the, proliferation, effectively, in, vitro])]). relacion([sujeto(['Withdrawal', of, 'SCF', or, treatment, with, imatinib]), verbo([induced]), complemento([apoptosis, of, 'KPAM1', cells])]). relacion([sujeto(['SCF']), verbo([activated]), complemento([the, 'RAS/MAPK', and, 'PI3K/AKT', 'pathways,', followed, by, downregulation, of, the, 'pro-apoptotic', factor, 'BIM', and, upregulation, of, the, 'anti-apoptotic', factor, 'MCL1'])]). relacion([sujeto(['Although', we]), verbo([found]), complemento([novel, missense, mutations, of, 'KIT', in, 2, of, 14, 'TL', 'patients,', neither, mutation, led, to, 'KIT', activation, and, neither, reduced, the, cytotoxic, effects, of, imatinib])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([the, essential, role, of, 'SCF/KIT', signaling, in, the, proliferation, of, 'DS-related', leukemia, and, the, possibility, of, therapeutic, benefits, of, imatinib, for, 'TL', patients])]). relacion([sujeto(['While', altered, 'GATA1']), verbo([inhibits]), complemento(['erythro-megakaryocytic', 'development,', less, is, known, about, how, trisomy, 21, impacts, blood, 'formation,', particularly, in, the, human, fetus, where, 'TMD', and, 'AMKL', originate])]). relacion([sujeto(['Remarkably,', trisomy, 21, progenitors, exhibited]), verbo([enhanced]), complemento([production, of, erythroid, and, megakaryocytic, cells, that, proliferated, excessively])]). relacion([sujeto(['Our', findings, indicate, that, trisomy, 21, itself, is]), verbo([associated]), complemento([with, 'cell-autonomous', expansion, of, 'erythro-megakaryocytic', progenitors])]). relacion([sujeto(['This', may, predispose, to, 'TMD', and, 'AMKL', by]), verbo([increasing]), complemento([the, pool, of, cells, susceptible, to, malignant, transformation, through, acquired, mutations, in, 'GATA1', and, other, cooperating, genes])]). relacion([sujeto(['To', evaluate, the, prognostic, significance, of, 'CEBPA', mutations, in, the, context, of, established, molecular, markers, in, cytogenetically, normal, '(', 'CN)', acute, myeloid, leukemia, '(', 'AML)', and]), verbo([gain]), complemento([biologic, insights, into, leukemogenesis, of, the, 'CN-AML', molecular, 'high-risk', subset, '(', 'FLT3', internal, tandem, duplication, '[', 'ITD]', positive, 'and/or', 'NPM1', wild, 'type)', that, has, a, significantly, higher, incidence, of, 'CEBPA', mutations, than, the, molecular, 'low-risk', subset, '(', 'FLT3-ITD', negative, and, 'NPM1', 'mutated)'])]). relacion([sujeto([9, ')', independently, of, other, molecular, and, clinical, characteristics, and, were]), verbo([associated]), complemento([with, unique, gene, and, miRNA, expression, profiles])]). relacion([sujeto(['The', major, features, of, these, profiles, were, upregulation, of, genes, '(', 'eg,', 'GATA1,', 'ZFPM1,', 'EPOR,', and, 'GFI1B)', and, miRNAs, '(', 'ie,', the, 'miR-181', 'family)']), verbo([involved]), complemento([in, erythroid, differentiation, and, downregulation, of, homeobox, genes])]). relacion([sujeto(['The', gene, and, miRNA, expression, profiling]), verbo([provided]), complemento([insights, into, leukemogenesis, of, the, 'CN-AML', molecular, 'high-risk', 'group,', indicating, that, 'CEBPA', mutations, are, associated, with, partial, erythroid, differentiation])]). relacion([sujeto(['Children', with, 'Down\'s', syndrome]), verbo([have]), complemento([a, greatly, increased, risk, of, acute, megakaryoblastic, and, acute, lymphoblastic, leukaemias])]). relacion([sujeto(['We', tested, the, hypothesis, that, mutations, in, 'JAK2', might, be, a, common, molecular, event, in, acute, lymphoblastic, leukaemia]), verbo([associated]), complemento([with, 'Down\'s', syndrome])]). relacion([sujeto(['Five', mutant, alleles, were, 'identified,', each, affecting, a, highly]), verbo([conserved]), complemento([arginine, residue, '(', 'R683)'])]). relacion([sujeto(['These', mutations, immortalised, primary, mouse, haematopoietic, progenitor, cells, in, 'vitro,', and]), verbo([caused]), complemento([constitutive, 'Jak/Stat', activation, and, 'cytokine-independent', growth, of, 'BaF3', 'cells,', which, was, sensitive, to, pharmacological, inhibition, with, 'JAK', inhibitor, 'I'])]). relacion([sujeto(['In', modelling, studies, of, the, 'JAK2', pseudokinase, 'domain,', 'R683', was, situated, in, an, exposed]), verbo([conserved]), complemento([region, separated, from, the, one, implicated, in, myeloproliferative, disorders])]). relacion([sujeto(['Somatically', acquired, 'R683', 'JAK2', mutations, define, a, distinct, acute, lymphoblastic, leukaemia, subgroup, that, is, uniquely]), verbo([associated]), complemento([with, trisomy, 21])]). relacion([sujeto(['The', proinflammatory, cytokine, tumor, necrosis, factor, alpha, '(', 'TNFalpha)']), verbo([has]), complemento([been, linked, to, 'inflammation-', and, 'cancer-related', 'anemia,', which, reduces, both, quality, of, life, and, prognosis, of, patients])]). relacion([sujeto(['The', aim, of, this, study, was, to]), verbo([reveal]), complemento([molecular, mechanisms, linked, to, the, inhibition, of, erythroid, differentiation, by, 'TNFalpha'])]). relacion([sujeto(['In', this, 'study,', we, showed, that, the, inhibition, of, erythropoietin, '(', 'Epo)-mediated', differentiation, by, 'TNFalpha']), verbo([lead]), complemento([to, a, downregulation, of, hemoglobin, synthesis, and, was, correlated, to, a, modulation, of, key, erythroid, transcription, factors])]). relacion([sujeto(['Thus,', a, reverse, of, the, transcription, factor, 'GATA-1/GATA-2', balance, normally, present, during, 'erythropoiesis,', as, well, as, a, downregulation, of, the, cofactor, of, 'GATA-1,', friend, of, 'GATA-1', '(', 'FOG-1),', and, the, coregulating, transcription, factor]), verbo([nuclear]), complemento([factor, erythroid, 2, '(', 'NF-E2)', was, observed, after, 'TNFalpha', treatment])]). relacion([sujeto(['These', changes]), verbo([led]), complemento([to, an, inhibition, of, erythroid, gene, expression, including, 'Epo', receptor, '(', 'EpoR),', 'alpha-', and, 'gamma-globin,', 'erythroid-associated', factor, '(', 'ERAF),', hydroxymethylbilane, synthetase, '(', 'HMBS),', and, glycophorin, 'A', '(', 'GPA)'])]). relacion([sujeto(['IFN', consensus, sequence]), verbo([binding]), complemento([protein, '(', 'Icsbp)', '(', 'IFN', response, 'factor-8)', is, a, hematopoietic, transcription, factor, with, dual, functions, in, myelopoiesis, and, immunity])]). relacion([sujeto(['In', this, 'study,', we]), verbo([report]), complemento([a, novel, role, of, 'Icsbp', in, regulating, the, development, of, eosinophils])]). relacion([sujeto(['Loss', of, 'Icsbp', in, mice]), verbo([leads]), complemento([to, a, reduction, of, eosinophils, in, different, tissues])]). relacion([sujeto(['Numbers', of, phenotypically, defined, eosinophil, progenitors, are]), verbo([decreased]), complemento([and, those, progenitors, 'have,', on, a, 'per-cell', 'basis,', reduced, eosinophil, differentiation, potential])]). relacion([sujeto(['The', transcription, factor, 'Gata1,', crucial, for, eosinophil, 'development,', is, reduced]), verbo([expressed]), complemento([in, committed, eosinophil, progenitors, in, wells, as, mature, eosinophils])]). relacion([sujeto(['With-no-lysine', 'kinase-4', '(', 'WNK4),', a, member, of, the, 'serine-threonine', protein, kinase, 'family,']), verbo([acts]), complemento([as, a, multifunctional, regulator, of, diverse, ion, transporters])]). relacion([sujeto(['We']), verbo([have]), complemento([previously, demonstrated, that, glucocorticoid, downregulates, human, 'WNK4', '(', 'hWNK4)', expression, through, the, negative, glucocorticoid, responsive, element])]). relacion([sujeto(['Analysis', of, the, transcriptional, activity, of, a, series, of, the, truncated, hWNK4, promoters, by, luciferase, assay, indicated, that, the, region, -, 484, to, -, 337, of, the, hWNK4, promoter, was, sensitive, to, 'TSA,', and, a, 'GATA-1']), verbo([binding]), complemento([motif, was, identified, at, position, -, 426, using, 'TRANSFAC-TESS', program])]). relacion([sujeto(['Moreover,', using, electrophoresis, mobility, shift, assay, and, chromatin, immunoprecipitation, 'assay,', the, 'GATA-1']), verbo([binding]), complemento([affinity, to, the, hWNK4, promoter, was, shown, to, increase, with, 'TSA', under, in, vitro, and, in, vivo, conditions])]). relacion([sujeto(['Immunoprecipitation', and, 'Western', blot, analyses, showed, that, the, levels, of, acetylated, 'GATA-1', were]), verbo([increased]), complemento([with, 'TSA,', in, agreement, with, changes, in, its, 'DNA-binding', affinity])]). relacion([sujeto(['These', findings, indicate, that, 'TSA']), verbo([induces]), complemento([hWNK4, 'expression,', at, least, in, 'part,', by, increasing, 'GATA-1', 'acetylation,', and, thereby, its, binding, to, the, 'GATA-1', responsive, 'element,', within, the, hWNK4, promoter])]). relacion([sujeto(['Proteins']), verbo([associated]), complemento([with, 'ODAG', were, isolated, by, 'pull-down', assay, in, conjugation, with, mass, spectrometry])]). relacion([sujeto(['EGFP', was]), verbo([expressed]), complemento([highly, in, the, presumptive, outer, nuclear, layer, and, weakly, in, the, presumptive, inner, nuclear, layer, in, the, 'ODAG', 'Tg', retina])]). relacion([sujeto(['Deregulated', expression, of, 'ODAG', in, the, eye]), verbo([induces]), complemento([elevated, intraocular, pressure, and, optic, nerve, atrophy, and, impairs, retinal, 'development,', possibly, by, interfering, with, the, 'Rab6/Rab6-GAP-mediated', signaling, pathway])]). relacion([sujeto(['These', results]), verbo([provide]), complemento([new, insights, into, the, mechanisms, regulating, ocular, 'development,', and, 'ODAG', 'Tg', would, be, a, novel, animal, model, for, human, diseases, caused, by, ocular, hypertension])]). relacion([sujeto(['The', transcription, factor, 'GATA-1']), verbo([participates]), complemento([in, programming, the, differentiation, of, multiple, hematopoietic, lineages])]). relacion([sujeto(['In', 'megakaryopoiesis,']), verbo([loss]), complemento([of, 'GATA-1', function, produces, complex, developmental, abnormalities, and, underlies, the, pathogenesis, of, megakaryocytic, leukemia, in, 'Down', syndrome])]). relacion([sujeto(['Megakaryocytic', induction, was]), verbo([associated]), complemento([with, dynamic, changes, in, endogenous, 'P-TEFb', 'composition,', including, recruitment, of, 'GATA-1', and, dissociation, of, 'HEXIM1,', a, 'Cdk9', inhibitor])]). relacion([sujeto(['P-TEFb']), verbo([has]), complemento([previously, been, implicated, in, promoting, elongation, of, paused, 'RNA', polymerase, 'II', and, in, programming, hypertrophic, differentiation, of, cardiomyocytes])]). relacion([sujeto(['Pulldown', assay, is, an, in, vitro, method, for, studies, of, 'protein-protein', 'interactions,', in, which, tagged, proteins, are, usually]), verbo([expressed]), complemento([as, the, bait, to, enrich, other, proteins, that, could, bind, to, them])]). relacion([sujeto(['In', most, 'cases,', the, 'GST', tag, could]), verbo([increase]), complemento([the, hydrophility, of, the, fusion, protein, and, help, to, avoid, the, formation, of, inclusion, bodies])]). relacion([sujeto(['However,', in, the, other, few, 'cases,', the]), verbo([target]), complemento([protein, may, be, strongly, hydrophobic, or, have, complicated, structures, that, were, hard, to, fold, and, assemble, in, correct, conformations, without, 'champerons,', and, even, the, existence, of, 'GST', tag, could, not, make, them, soluble])]). relacion([sujeto(['These', proteins, were, always]), verbo([expressed]), complemento([as, inclusion, bodies, and, had, no, functions])]). relacion([sujeto(['LMO2', was, a, small, molecular, weight, and, insoluble, 'protein,', in, this, 'study,', 'GST', system, and, 'MBP', system, were, used, to]), verbo([express]), complemento(['GST-LMO2', and, 'MBP-LMO2', fusion, 'proteins,', respectively])]). relacion([sujeto(['We']), verbo([found]), complemento([that, 'GST-LMO2', fusion, protein, was, expressed, as, inclusion, bodies, whereas, 'MBP-LMO2', fusion, protein, was, expressed, in, soluble, form])]). relacion([sujeto(['Western', blot, analyses, showed, that, both, of, these, proteins, could]), verbo([bind]), complemento([to, endogenous, 'GATA1', in, 'K562', 'cells,', but, recovered, 'GATA1', protein, by, 'MBP-LMO2', fusion, protein, was, much, more, than, 'GST-LMO2', fusion, protein])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, using, of, 'MBP', system, is, a, helpful, attempt, in, the, case, of, studying, small, molecular, 'weight,', strong, hydrophobic, proteins])]). relacion([sujeto(['Mechanisms', explaining, the, cellular, basis, for, 'D6', function]), verbo([have]), complemento([been, based, on, 'D6', expression, by, lymphatic, endothelial, cells])]). relacion([sujeto(['In', this, 'study,', we, demonstrate, that, functional, 'D6', is, also]), verbo([expressed]), complemento([by, murine, and, human, hemopoietic, cells, and, that, this, expression, can, be, regulated, by, 'pro-', and, 'anti-inflammatory', agents])]). relacion([sujeto(['We', propose, a, model, for, 'D6', function, in, which, 'leukocytes,', within, inflamed, 'sites,']), verbo([activate]), complemento(['D6', expression, and, thus, trigger, resolution, of, inflammatory, responses])]). relacion([sujeto(['Our', data, on, 'D6', expression, by, circulating, 'DCs', and, 'B', cells, also]), verbo([suggest]), complemento([alternative, roles, for, 'D6,', perhaps, in, the, coordination, of, innate, and, adaptive, immune, responses])]). relacion([sujeto(['These', data, therefore, alter, our, models, of, in, vivo, 'D6', function, and]), verbo([suggest]), complemento([possible, 'discrete,', and, 'novel,', roles, for, 'D6', on, lymphatic, endothelial, cells, and, leukocytes])]). relacion([sujeto(['Human', parvovirus, 'B19', infection, is, responsible, for, a, wide, range, of, human, diseases, ranging, from, mild, erythema, infectiosum, in, immunocompetent, children, to, fetal]), verbo([loss]), complemento([in, primary, infected, pregnant, women, and, aplastic, anemia, or, lethal, cytopenias, in, adult, immunocompromised, patients])]). relacion([sujeto(['Since', persistent, viral, infection, is, responsible, for, an, autoimmune, response, and, clinical, symptoms, can, mimic, autoimmune, inflammatory, 'disorders,', parvovirus, 'B19', is, the, object, of, intense, efforts, to, clarify, whether, it, is, also, able, to]), verbo([trigger]), complemento([autoimmune, diseases])]). relacion([sujeto(['Indeed', the, virus]), verbo([has]), complemento([been, implicated, as, the, causative, or, the, precipitating, agent, of, several, autoimmune, disorders, including, rheumatoid, 'arthritis,', systemic, 'lupus,', antiphospholipid, 'syndrome,', systemic, sclerosis, and, vasculitides])]). relacion([sujeto(['Molecular', mimicry, between, host, and, viral, proteins, seems, to, be, the, main, mechanism]), verbo([involved]), complemento([in, the, induction, of, autoimmunity])]). relacion([sujeto(['By', means, of, a, random, peptide, library, 'approach,', we]), verbo([have]), complemento([identified, a, peptide, that, shares, homology, with, parvovirus, 'VP1', protein, and, with, human, cytokeratin])]). relacion([sujeto(['Our', data, show, that, despite]), verbo([expressing]), complemento([similar, hESC, markers, under, 'self-renewing', conditions, and, initiating, mesodermal, differentiation, under, spontaneous, differentiation, 'conditions,', marked, differences, in, subsequent, hematopoietic, differentiation, potential, among, these, lines, existed])]). relacion([sujeto(['Interestingly,', 'H1', and, 'BG02', displayed, remarkable, similarities, in, their, kinetics, of, hematopoietic, marker, 'expression,', hematopoietic, colony, 'formation,', erythroid, 'differentiation,', and, globin, 'expression,']), verbo([suggesting]), complemento([that, a, 'similar,', predetermined, differentiation, sequence, is, followed])]). relacion([sujeto(['Down', syndrome, '(', 'DS)', children]), verbo([have]), complemento([a, high, frequency, of, acute, megakaryoblastic, leukemia, '(', 'AMKL)', in, early, childhood])]). relacion([sujeto(['In', all, 'DS', fetal, livers, '(', 'FLs),', but, not, 'marrows,', 'megakaryocyte-erythroid', progenitor, frequency, was]), verbo([increased]), complemento(['(', 55.9, '%', +, /, -, 4, '%', vs, 17.1, '%', +, /, -, 3, '%', ',', 'CD34(+)CD38(+)', 'cells;', 'P', &, 'lt;'])]). relacion([sujeto(['Clonogenicity', of, 'DS-FL', versus, normal, 'FL', 'CD34(+)', cells, was, markedly]), verbo([increased]), complemento(['(', 78, '%', +, /, -, 7, '%', vs, 15, '%', +, /, -, 3, '%', ')', affecting, 'megakaryocyte-erythroid', '(', approximately, 7, -, fold, 'higher)', and, 'GM', and, 'colony-forming', 'unit-granulocyte,', erythrocyte, 'macrophage,', megakaryocyte, '(', 'CFU-GEMM)', progenitors])]). relacion([sujeto(['These', data, indicate, that, 'T21', itself, profoundly, disturbs, 'FL', hemopoiesis, and, they]), verbo([provide]), complemento([a, testable, hypothesis, to, explain, the, increased, susceptibility, to, 'GATA1', mutations, in, 'DS-AMKL', and, 'DS-associated', transient, myeloproliferative, disorder])]). relacion([sujeto(['Expression', of, either, 'K-rasC40', that, links, to, phosphoinositide, 3, -, kinase, '(', 'PI3K)', 'activation,', or, 'Akt2', that]), verbo([acts]), complemento([downstream, of, 'PI3K,', could, rescue, both, hematopoietic, and, angiogenic, defects, in, the, 'K-ras', knockdown])]). relacion([sujeto(['Consistently,', the, functional, rescue, by, 'k-ras', mRNA, was, significantly]), verbo([suppressed]), complemento([by, 'wortmannin,', a, 'PI3K-specific', inhibitor])]). relacion([sujeto(['Our', results]), verbo([provide]), complemento([direct, evidence, that, 'PI3K-Akt', plays, a, crucial, role, in, mediating, 'K-ras', signaling, during, hematopoiesis, and, angiogenesis, in, 'vivo,', thus, offering, new, targets, and, alternative, vertebrate, model, for, studying, these, processes, and, their, related, diseases])]). relacion([sujeto(['This', study]), verbo([found]), complemento([that, that, in, iron, 'deficiency,', fetal, definitive, erythropoiesis, is, inhibited, at, the, basophilic, erythroblast, stage, with, increased, proliferation, and, elevated, apoptosis])]). relacion([sujeto(['Microarray', gene, profiling, analysis, showed, that, 'HRI', was]), verbo([required]), complemento([for, adaptive, gene, expression, in, erythroid, precursors, during, chronic, iron, deficiency])]). relacion([sujeto(['Many', of, these, genes, are]), verbo([regulated]), complemento([by, 'Gata1', and, 'Fog1'])]). relacion([sujeto(['We', demonstrate, for, the, first, time, that, 'Gata1', expression, in, developing, erythroid, precursors, is]), verbo([decreased]), complemento([in, iron, 'deficiency,', and, is, decreased, further, in, combined, iron, and, 'HRI', deficiencies])]). relacion([sujeto(['Additionally,', 'Fog1', expression, is]), verbo([decreased]), complemento([in, combined, 'deficiencies,', but, not, in, iron, or, 'HRI', deficiency, alone])]). relacion([sujeto(['Our', results, indicate, that, 'HRI']), verbo([confers]), complemento([adaptive, gene, expression, in, developing, erythroblasts, during, iron, deficiency, through, maintaining, 'Gata1/Fog1', expression])]). relacion([sujeto(['Chromatin', from, different, regions, of, the, genome, frequently, forms, steady, associations, that, play, important, roles, in]), verbo([regulating]), complemento([gene, expression])]). relacion([sujeto(['Here,', we, describe, a, new, 'strategy,', quantitative]), verbo([associated]), complemento([chromatin, trap, '(', 'QACT),', which, incorporates, a, modified, 3, 'C', method, and, a, quantitative, assay, 'tool,', to, capture, and, quantitatively, analyzes, all, possible, associated, chromatin, partners, '(', 'ACPs)', of, a, given, chromatin, fragment])]). relacion([sujeto(['Using', 'QACT,', we]), verbo([have]), complemento([analyzed, the, chromatin, conformation, of, the, mouse, 'alpha-globin', gene, cluster, and, proved, the, extensive, interaction, between, 'HS26', and, 'alpha-globin', genes])]). relacion([sujeto(['In', 'addition,', we]), verbo([have]), complemento([identified, a, candidate, 'alpha1-globin', gene, specific, silencer, 475, 'A8', which, shows, the, 'differentiation-stage', specific, 'DNase', 'I', hypersensitivity])]). relacion([sujeto(['Functional', analysis]), verbo([suggests]), complemento([that, 475, 'A8', may, regulate, the, 'alpha1-globin', gene, during, terminal, differentiation, of, committed, erythroid, progenitor, cells])]). relacion([sujeto(['ChIP', '(', chromatin, 'immunoprecipitation)', and, cotransfection, assays, demonstrate, that, 'GATA-1,', a, hemopoietic, specific, transcriptional, 'factor,', may]), verbo([increase]), complemento(['alpha1-globin', gene, expression, by, suppressing, the, function, of, 475, 'A8', in, terminally, differentiated, erythroid, cells])]). relacion([sujeto(['Gene', expression, analyses]), verbo([have]), complemento([led, to, a, better, understanding, of, growth, control, of, prostate, cancer, cells])]). relacion([sujeto(['We', and, others]), verbo([have]), complemento([identified, the, presence, of, several, zinc, finger, transcription, factors, in, the, neoplastic, 'prostate,', suggesting, a, potential, role, for, these, genes, in, the, regulation, of, the, prostate, cancer, transcriptome])]). relacion([sujeto(['To', rapidly, identify, coordinately]), verbo([expressed]), complemento([prostate, cancer, growth, control, genes, that, may, be, regulated, by, 'WT1,', we, used, an, in, silico, approach])]). relacion([sujeto(['Evolutionary']), verbo([conserved]), complemento([transcription, factor, binding, sites, '(', 'TFBS)', recognized, by, 'WT1,', 'EGR1,', 'SP1,', 'SP2,', 'AP2', and, 'GATA1', were, identified, in, the, promoters, of, 24, differentially, expressed, prostate, cancer, genes, from, eight, mammalian, species])]). relacion([sujeto(['To', test, the, relationship, between, sequence, conservation, and, 'function,', chromatin, of, 'LNCaP', prostate, cancer, and, kidney, 293, cells, were, tested, for, 'TF']), verbo([binding]), complemento([using, chromatin, immunoprecipitation, '(', 'ChIP)'])]). relacion([sujeto(['Multiple', putative, 'TFBS', in, gene, promoters, of, placental, mammals, were]), verbo([found]), complemento([to, be, shared, with, those, in, human, gene, promoters, and, some, were, conserved, between, genomes, that, diverged, about, 170, million, years, ago, '(', i])]). relacion([sujeto([',', primates, and, 'marsupials),', therefore, implicating, these, sites, as, candidate]), verbo([binding]), complemento([sites])]). relacion([sujeto(['Among', those, genes, coordinately]), verbo([expressed]), complemento([with, 'WT1', was, the, 'kallikrein-related', peptidase, 3, '(', 'KLK3)', gene, commonly, known, as, the, prostate, specific, antigen, '(', 'PSA)', gene])]). relacion([sujeto(['This', analysis, located, several, potential, 'WT1', 'TFBS', in, the, 'PSA', gene, promoter, and]), verbo([led]), complemento([to, the, rapid, identification, of, a, novel, putative, binding, site, confirmed, in, vivo, by, 'ChIP'])]). relacion([sujeto(['Conversely', for, two, prostate, growth, control, 'genes,', androgen, receptor, '(', 'AR)', and, vascular, endothelial, growth, factor, '(', 'VEGF),', known, to, be, transcriptionally]), verbo([regulated]), complemento([by, 'WT1,', regulatory, sequence, conservation, was, observed, and, 'TF', binding, in, vivo, was, confirmed, by, 'ChIP'])]). relacion([sujeto(['Overall,', this]), verbo([targeted]), complemento([approach, rapidly, identified, important, candidate, 'WT1-binding', elements, in, genes, coordinately, expressed, with, 'WT1', in, prostate, cancer, 'cells,', thus, enabling, a, more, focused, functional, analysis, of, the, most, likely, target, genes, in, prostate, cancer, progression])]). relacion([sujeto(['Loss', of, 'GATA1', function, results, in, excessive, megakaryocyte, proliferation, and, disordered, terminal, platelet, 'maturation,']), verbo([leading]), complemento([to, thrombocytopenia, and, leukemia, in, patients])]). relacion([sujeto(['We']), verbo([have]), complemento([used, in, vivo, biotinylated, 'GATA1', to, isolate, megakaryocyte, 'GATA1-partner', proteins])]). relacion([sujeto(['Here,', several, independent, approaches, show, that, 'GATA1']), verbo([interacts]), complemento([with, several, proteins, in, the, megakaryocyte, cell, line, 'L8057', and, in, primary, megakaryocytes])]). relacion([sujeto(['Knockdown', of, 'ETO2', expression]), verbo([promotes]), complemento([megakaryocyte, differentiation, and, enhances, expression, of, select, genes, expressed, in, terminal, megakaryocyte, 'maturation,', 'eg,', platelet, factor, 4, '(', 'Pf4)'])]). relacion([sujeto(['ETO2-dependent', direct, repression, of, the, 'Pf4', proximal, promoter, is]), verbo([mediated]), complemento([by, 'GATA-binding', sites, and, an, 'E-Box', motif])]). relacion([sujeto(['Consistent', with, 'this,', endogenous, 'ETO2,', 'GATA1,', and, the, 'SCL', pentameric, complex, all, specifically]), verbo([bind]), complemento([the, promoter, in, vivo])]). relacion([sujeto(['Finally,', as, 'ETO2', expression, is, restricted, to, immature, 'megakaryocytes,', these, data]), verbo([suggest]), complemento([that, 'ETO2', directly, represses, inappropriate, early, expression, of, a, subset, of, terminally, expressed, megakaryocyte, genes, by, binding, to, 'GATA1', and, 'SCL'])]). relacion([sujeto(['Semenogelin', '(', 'SEMG)', 'I', is, a, 'cancer-testis', antigen]), verbo([expressed]), complemento([in, myeloma, cells])]). relacion([sujeto(['We']), verbo([found]), complemento([that, nucleotide, sequences, spanning, the, two, putative, 'GATA-1', binding, domains, are, vital, for, the, primary, regulation, of, 'SEMG', 'I', promoter, function, while, the, other, parts, of, the, promoter, sequence, are, responsible, for, the, fine, adjustment, of, the, core, promoter, function])]). relacion([sujeto(['The', core, promoter, sequence, is, responsive, to, the]), verbo([enhancing]), complemento([effect, of, 'IL-4', and, 'IL-6'])]). relacion([sujeto(['The', 'Runx1/AML1', transcription, factor, is]), verbo([required]), complemento([for, the, generation, of, hematopoietic, stem, cells, and, is, one, of, the, most, frequently, targeted, genes, in, human, leukemia])]). relacion([sujeto(['This', observation, sheds, new, light, on, the, 'mechanism(s)', that]), verbo([regulate]), complemento([the, activity, of, 'Runx', transcription, factors])]). relacion([sujeto(['GATA-1', is, an, erythroid, activator, that]), verbo([binds]), complemento(['beta-globin', gene, promoters, and, 'DNase', 'I', hypersensitive, sites, '(', 'HSs)', of, the, 'beta-globin', locus, control, region, '(', 'LCR)'])]). relacion([sujeto(['We', investigated, the, direct, role, of, 'GATA-1', interaction, at, the, 'LCR', 'HS2', enhancer, by, mutating, its]), verbo([binding]), complemento([sites, within, minichromosomes, in, erythroid, cells])]). relacion([sujeto(['Loss', of, 'GATA-1', in, 'HS2', did, not, compromise, interaction, of, 'NF-E2,', a, second, activator, that]), verbo([binds]), complemento([to, 'HS2,', nor, was, 'DNase', 'I', hypersensitivity, at, 'HS2', or, the, promoter, of, a, linked, 'epsilon-globin', gene, altered])]). relacion([sujeto(['Transcription', of, 'epsilon-globin', was, severely, compromised, with]), verbo([loss]), complemento([of, 'RNA', pol, 'II', from, the, transcription, start, site, and, reduction, of, 'H3', acetylation, and, 'H3K4', 'di-', and, 'tri-methylation', in, coding, sequences])]). relacion([sujeto(['In', 'contrast,', widespread, detection, of, 'H3K4', 'mono-methylation', was, unaffected, by]), verbo([loss]), complemento([of, 'GATA-1', in, 'HS2'])]). relacion([sujeto(['These', results, support, the, idea, that, 'GATA-1', interaction, in, 'HS2']), verbo([has]), complemento([a, prominent, and, direct, role, in, 'co-activator', and, pol, 'II', recruitment, conferring, active, histone, tail, modifications, and, transcription, activation, to, a, target, gene, but, that, it, does, 'not,', by, 'itself,', play, a, major, role, in, establishing, 'DNase', 'I', hypersensitivity])]). relacion([sujeto(['The', adult, erythron, is]), verbo([maintained]), complemento([via, dynamic, modulation, of, erythroblast, survival, potentials])]). relacion([sujeto(['Stage-to-stage']), verbo([modulated]), complemento([genes, were, then, functionally, 'categorized,', with, a, focus, on, apoptotic, factors])]). relacion([sujeto(['Among', hematopoietic, 'lineages,', 'DAPK2', was]), verbo([expressed]), complemento([predominantly, in, erythroid, cells])]). relacion([sujeto(['In', 'UT7epo', 'cells,', siRNA, 'knock-down', of, 'DAPK2']), verbo([enhanced]), complemento([survival, due, to, cytokine, 'withdrawal,', and, 'DAPK2\'s', phosphorylation, and, kinase, activity, also, were, erythropoietin, '(', 'EPO)-modulated'])]). relacion([sujeto(['Inhibitors', of, 'DNA']), verbo([binding]), complemento(['(', 'Id)', family, members, are, key, regulators, of, cellular, differentiation, and, proliferation])]). relacion([sujeto(['As', negative, regulators, of, 'E', 'proteins,', 'Id', proteins]), verbo([have]), complemento([been, implicated, in, lymphocyte, development])]). relacion([sujeto(['Overexpression', of, 'Id1,', 'Id2,', or, 'Id3']), verbo([has]), complemento([similar, effects, on, lymphocyte, development])]). relacion([sujeto(['Knock-down', of, 'Id2', by, shRNA, in, hematopoietic, progenitor, cells]), verbo([promoted]), complemento(['B-cell', differentiation, and, induced, the, expression, of, 'B-cell', 'lineage-specific', genes])]). relacion([sujeto(['Overexpression', of, 'Id2']), verbo([enhanced]), complemento([erythroid, 'development,', and, decreased, level, of, 'Id2', impaired, normal, erythroid, development])]). relacion([sujeto(['Id2', regulation, of, erythroid, development, is]), verbo([mediated]), complemento([via, interacting, with, transcription, factor, 'PU'])]). relacion([sujeto([1, and]), verbo([modulating]), complemento(['PU'])]). relacion([sujeto(['We', conclude, that, 'Id2']), verbo([regulates]), complemento([lymphoid, and, erythroid, development, via, interaction, with, different, target, proteins])]). relacion([sujeto([cDNAs, encoding, for, the, angiogenic, markers, fli1, and, 'flk1,', and, for, the, hematopoietic, markers, gata1, and, 'gata2,', were, identified, from, an]), verbo([expressed]), complemento([sequence, tag, library, of, rainbow, trout])]). relacion([sujeto(['Results', show, that, 'fli1,', flk1, and, gata2, are]), verbo([activated]), complemento([in, bilateral, bands, of, the, lateral, trunk, mesoderm, before, the, onset, of, 'somitogenesis,', shortly, followed, by, gata1])]). relacion([sujeto(['Subsequent', axial, vasculogenesis, and, initial, blood, cell, formation]), verbo([involve]), complemento([a, clear, spatial, separation, of, fli1, and, gata, gene, expression])]). relacion([sujeto(['Fli1', staining, is, most, intense, within, the, axial, vessel, '(', dorsal, 'aorta,', posterior, cardinal, 'vein)', forming, and, lateral, 'ICM', 'cells,', whereas]), verbo([binding]), complemento([of, gata1, and, gata2, probes, becomes, confined, to, the, central, portion, of, 'ICM', cells, beneath, the, dorsal, aorta])]). relacion([sujeto(['Further', angiogenesis, and, hematopoiesis, are]), verbo([activated]), complemento([in, the, &, 'quot;posterior', 'ICM"', of, the, tail])]). relacion([sujeto([1, reduced, expression, of, 'scl,', 'lmo2,', 'c-myb,', 'mpo,', 'rag1,', gata1, and, hemoglobin, alpha, 'embryonic-1', '(', 'hbae1),', as, well, as, the, total, amount, of, embryonic, 'hemoglobin,', but]), verbo([increased]), complemento([expression, of, pu])]). relacion([sujeto(['Under', the, same, 'conditions,', 'MO', injection, did, not, affect, the, markers]), verbo([involved]), complemento([in, vascular, and, pronephric, development])]). relacion([sujeto([1, via, mRNA, injection]), verbo([enhanced]), complemento([expression, of, gata1, but, inhibited, expression, of, pu])]). relacion([sujeto(['These', findings]), verbo([suggest]), complemento([that, 'Gfi1'])]). relacion([sujeto([1, plays, a, critical, role, in]), verbo([regulating]), complemento([the, balance, of, embryonic, erythroid, and, myeloid, lineage, 'determination,', and, is, also, required, for, the, differentiation, of, lymphocytes, and, granulocytes, during, zebrafish, embryogenesis])]). relacion([sujeto(['This', slow, relaxation, is, described, by, a, gaussian, mixture, model, that, incorporates, 'noise-driven', transitions, between, discrete, 'subpopulations,']), verbo([suggesting]), complemento([hidden, 'multi-stability', within, one, cell, type])]). relacion([sujeto(['Although', their, unique, gene, expression, profiles, eventually, reverted, to, that, of, the, median, 'cells,']), verbo([revealed]), complemento([an, attractor, 'state,', they, lasted, long, enough, to, confer, a, greatly, different, proclivity, for, choosing, either, the, erythroid, or, the, myeloid, lineage])]). relacion([sujeto(['Preference', in, lineage, choice, was]), verbo([associated]), complemento([with, increased, expression, of, 'lineage-specific', transcription, 'factors,', such, as, a, &, 'gt;200-fold', increase, in, 'Gata1', '(', ref])]). relacion([sujeto([10, ')', among, the, 'erythroid-prone', 'cells,', or, a, &, 'gt;15-fold']), verbo([increased]), complemento(['PU'])]). relacion([sujeto(['Eosinophils']), verbo([have]), complemento([been, implicated, as, playing, a, major, role, in, allergic, airway, responses])]). relacion([sujeto(['However,', the, importance, of, these, cells, to, the, development, of, this, disease]), verbo([has]), complemento([remained, ambiguous, despite, many, 'studies,', partly, because, of, lack, of, appropriate, model, systems])]). relacion([sujeto(['We']), verbo([report]), complemento(['that,', in, contrast, to, results, obtained, on, a, 'BALB/c', 'background,', 'eosinophil-deficient', 'C57BL/6', 'Delta', dblGATA, mice, '(', 'eosinophil-null', mice, via, the, 'Delta', 'DblGATA1', 'mutation)', have, reduced, airway, 'hyperresponsiveness,', and, cytokine, production, of, interleukin, '(', 'IL)-4,', -, 5, ',', and, -, 13, in, 'ovalbumin-induced', allergic, airway, inflammation])]). relacion([sujeto(['This', was]), verbo([caused]), complemento([by, reduced, 'T', cell, recruitment, into, the, 'lung,', as, these, mouse, lungs, had, reduced, expression, of, 'CCL7/MCP-3,', 'CC11/eotaxin-1,', and, 'CCL24/eotaxin-2'])]). relacion([sujeto(['These', studies, indicate, that, on, the, 'C57BL/6', 'background,', eosinophils, are, integral, to, the, development, of, airway, allergic, responses, by]), verbo([modulating]), complemento([chemokine, 'and/or', cytokine, production, in, the, 'lung,', leading, to, 'T', cell, recruitment])]). relacion([sujeto(['Comparison', of, normal, erythroblasts, and, erythroblasts, from, persons, with, the, rare, 'In(Lu)', type, of, 'Lu(a-b-)', blood, group, phenotype, showed]), verbo([increased]), complemento([transcription, levels, for, 314, genes, and, reduced, levels, for, 354, genes, in, 'In(Lu)', cells])]). relacion([sujeto(['Many', 'erythroid-specific', genes, '(', including, 'ALAS2,', 'SLC4A1)', had, reduced, transcript, 'levels,']), verbo([suggesting]), complemento([the, phenotype, resulted, from, a, transcription, factor, abnormality])]). relacion([sujeto(['One', mutation, abolished, a, 'GATA1']), verbo([binding]), complemento([site, in, the, 'EKLF', promoter, '(', -, 124, 'T>C)'])]). relacion([sujeto(['Two', mutations, '(', 'Leu127X;', 'Lys292X)', resulted, in, premature, termination, 'codons,', 2, '(', 'Pro190LeufsX47;', 'Arg319GlufsX34)', in, 'frameshifts,', and, 4, in, amino, acid, substitution, of]), verbo([conserved]), complemento([residues, in, zinc, finger, domain, 1, '(', 'His299Tyr)', or, domain, 2, '(', 'Arg328Leu;', 'Arg328His;', 'Arg331Gly)'])]). relacion([sujeto(['Persons', with, the, 'In(Lu)', phenotype]), verbo([have]), complemento([no, reported, 'pathology,', indicating, that, one, functional, 'EKLF', allele, is, sufficient, to, sustain, human, erythropoiesis])]). relacion([sujeto(['These', data]), verbo([provide]), complemento([the, first, description, of, inactivating, mutations, in, human, 'EKLF', and, the, first, demonstration, of, a, blood, group, phenotype, resulting, from, mutations, in, a, transcription, factor])]). relacion([sujeto(['Apoptosis', '(', 'TUNEL', 'assay),', 'BM', architecture, organization, '(', scanning, electronic, 'microscopy),', proliferation, '(', 'DNA', 'assay),', differentiation, '(', clonogenic, 'cultures),', expression, of, survival, erythroid, related, proteins, '(', 'EPO-R,', 'GATA-1,', 'Bcl-xL)', as, well, as, the, expression, of, 'apoptotic-', related, proteins, '(', 'Bax,']), verbo([activated]), complemento(['Caspase-3)', by, 'Western', 'blotting,', were, evaluated])]). relacion([sujeto(['Experimental', data, showed, that, 'apoptosis,']), verbo([arrest]), complemento([of, cell, proliferation, and, disruptions, of, 'BM', architecture, were, maximal, within, the, first, period, of, acute, stress, '(', 1, -, 3, 'days)'])]). relacion([sujeto(['Moreover,', from, day, 5, upon, drug, challenge, 'BM']), verbo([responds]), complemento([to, acute, stress, through, the, 'EPO-EPO-R', 'system,', prompting, expressions, of, 'GATA-1', and, 'Bcl-xL'])]). relacion([sujeto(['Erythroid', proliferation, rates, and, 'red-cell-committed', progenitors]), verbo([enhanced]), complemento([in, a, coordinated, way, to, restore, the, size, and, function, of, the, red, cell, compartment])]). relacion([sujeto(['Together,', these, results, indicate, that, in, response, to, acute, stress, a, dramatic]), verbo([increase]), complemento([in, 'CFU-E', '(', erythroid, colony, forming, 'units)', population, is, concomitant, with, upregulation, of, 'EPO-R,', 'GATA-1', and, 'Bcl-xL', in, the, 'BM', erythroid, 'compartment,', and, that, these, concurrent, processes, are, crucial, for, acquiring, proper, erythroid, cell, functionality, without, delayed, response, to, tissular, hypoxia])]). relacion([sujeto(['We']), verbo([have]), complemento([analyzed, single, nucleotide, polymorphisms, '(', 'SNPs)', in, the, 'XPC,', 'XPA,', and, 'XPG', genes, of, the, nucleotide, excision, repair, '(', 'NER)', pathway, in, the, 'Indian', population])]). relacion([sujeto(['In', silico, 'PCR', analysis, demonstrated, that, all, three, novel, polymorphisms, lie, within, a, putative, 'CpG', island, and, that, the, variation, at, position, 1418, falls, within, the, potential, 'GATA1/2/3', transcription, 'factor(s)']), verbo([binding]), complemento([site, and, also, within, the, negative, control, element])]). relacion([sujeto(['We', performed, a, gel, retardation, assay, with, 'HeLa', cell]), verbo([nuclear]), complemento([extract, with, an, oligonucleotide, encompassing, this, region])]). relacion([sujeto(['One', of, the, alleles]), verbo([found]), complemento([at, position, 1458, of, the, 'XPA', gene, showed, a, significant, change, in, 'protein-DNA', interaction])]). relacion([sujeto(['In', the, 'XPG', gene, we]), verbo([found]), complemento([five, polymorphisms, in, the, coding, region, and, one, each, in, the, 5, '\'', 'UTR', of, exon, 1, and, in, intron, 13])]). relacion([sujeto(['Experimental', perturbation, of, signaling, or, transcription, factor, networks]), verbo([has]), complemento([been, used, to, study, the, developmental, potential, of, lymphoid, 'progenitors,', 'lineage-committed', precursors, and, mature, lymphocytes])]). relacion([sujeto(['Forced', 'C/EBPalpha', expression, furthermore]), verbo([induces]), complemento([direct, transdifferentiation, of, immature, thymocytes, or, 'B', cells, into, macrophages])]). relacion([sujeto(['Together', these, experiments]), verbo([have]), complemento([uncovered, an, unanticipated, developmental, plasticity, of, 'lymphocytes,', which, may, account, for, lineage, switches, observed, in, human, malignancies])]). relacion([sujeto(['According', to, the, currently, prevailing, 'perception,', sporadic, cancer, arises, as, a, result, of, somatic, mutations, in, a, cell, that]), verbo([lead]), complemento([to, its, uncontrolled, proliferation])]). relacion([sujeto(['For', 'instance,', evidence, gathered, from, 'Down', syndrome, '(', 'DS)', individuals]), verbo([has]), complemento([challenged, the, above, perceived, explanation, since, somatic, mutations, in, these, patients, markedly, differ, from, those, arisen, in, the, general, 'population,', and, do, not, seem, to, occur, at, random])]). relacion([sujeto(['There', is, no, global]), verbo([increase]), complemento([or, decrease, of, somatic, mutations, in, all, genes, in, 'DS'])]). relacion([sujeto(['Instead,', specific, mutations]), verbo([have]), complemento([been, detected, on, particular, 'loci,', depending, on, the, tissue, type, and, the, age, of, the, 'DS', person])]). relacion([sujeto(['In', the, context, of, constitutional, trisomy, 21, ',', where, cancer]), verbo([have]), complemento([a, very, particular, and, striking, 'distribution,', 'biochemical,', physiological, and, architectural, imbalances, in, specific, tissues, may, be, responsible, for, a, vulnerable, state, leading, to, carcinogenesis])]). relacion([sujeto(['Conversely,', in, tissues, of, 'DS', patients, which, seem, resistant, to, 'cancer,', the, proliferative, and, maturation, state, of, the, cells, would]), verbo([lead]), complemento([to, a, refractory, state, of, neoplastic, transformation])]). relacion([sujeto(['Experimentally,', we, observed, that, the, proliferation, of, tumor, cells, in, extracellular, matrix, produced, by, trisomic, 21, fibroblasts, appears, to, be]), verbo([inhibited]), complemento([when, compared, to, that, of, those, placed, on, an, extracellular, matrix, produced, by, euploid, fibroblasts])]). relacion([sujeto(['These', observations, challenge, the, current, somatic, mutation, theory, of, 'carcinogenesis,', and, strongly]), verbo([suggest]), complemento([instead, a, critical, role, of, cells, and, tissues, in, the, microenvironment, where, carcinogenesis, occurs])]). relacion([sujeto(['The', hierarchical, progression, of, stem, and, progenitor, cells, to, their, 'more-committed', progeny, is]), verbo([mediated]), complemento([through, 'cell-to-cell', signaling, pathways, and, intracellular, transcription, factor, activity])]). relacion([sujeto(['Applying', phylogenetic, footprinting, and, in, vivo]), verbo([binding]), complemento([studies, in, combination, with, newly, developed, 'loss-of-function', technology, in, embryoid, 'bodies,', we, find, that, 'Gata2', and, 'Smad5', cooperate, to, induce, 'Eklf', in, a, progenitor, 'population,', followed, by, a, switch, to, 'Gata1-controlled', regulation, of, 'Eklf', transcription, upon, erythroid, commitment])]). relacion([sujeto(['Thus,', understanding, the, regulation, of, 'gamma-globin', gene, expression, and, its, silencing, in, adults]), verbo([has]), complemento([potential, therapeutic, implications])]). relacion([sujeto(['We', studied, a, father, and]), verbo([son]), complemento([in, an, 'Iranian-American', family, who, had, elevated, 'Hb', 'F', levels, and, found, a, novel, 'T-to-G', transversion, at, nucleotide, '(', 'nt)', -, 567, of, the, 'HBG2', promoter])]). relacion([sujeto(['This', mutation, alters, a, 'GATA-1']), verbo([binding]), complemento([motif, to, a, 'GAGA', sequence, located, within, a, previously, identified, silencing, element])]). relacion([sujeto(['DNA-protein']), verbo([binding]), complemento([assays, showed, that, the, 'GATA', motif, of, interest, is, capable, of, binding, 'GATA-1', transcription, factor, in, vitro, and, in, vivo])]). relacion([sujeto(['In', 'addition,', the, 'T-to-G', mutation, at, the, 'GATA', motif]), verbo([increased]), complemento([the, promoter, activity, by, 'two-', to, threefold, in, transiently, transfected, erythroid, cell, lines])]). relacion([sujeto(['The']), verbo([binding]), complemento([motif, is, uniquely, conserved, in, simian, primates, with, a, fetal, pattern, of, 'gamma-globin', gene, expression])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, the, 'GATA', motif, under, study, has, a, functional, role, in, silencing, 'gamma-globin', gene, expression, in, adults])]). relacion([sujeto(['The', 'T-to-G', mutation, in, this, motif, disrupts, 'GATA-1']), verbo([binding]), complemento([and, the, associated, repressor, 'complex,', abolishing, its, silencing, effect, and, resulting, in, the, 'up-regulation', of, 'gamma-globin', gene, expression, in, adults])]). relacion([sujeto(['Although', it]), verbo([has]), complemento([been, proposed, that, the, common, myeloid, progenitor, gives, rise, to, 'granulocyte/monocyte', progenitors, and, 'megakaryocyte/erythroid', progenitors, '(', 'MEP),', little, is, known, about, molecular, switches, that, determine, whether, 'MEPs', develop, into, either, erythrocytes, or, megakaryocytes])]). relacion([sujeto(['We']), verbo([have]), complemento([identified, signal, transducer, and, activator, of, transcription, 5, '(', 'STAT5)', as, a, critical, denominator, that, determined, lineage, commitment, between, erythroid, and, megakaryocytic, cell, fates])]). relacion([sujeto(['Depletion', of, 'STAT5', from, 'CD34(+)', cells, by, a, lentiviral, 'RNAi', approach, in, the, presence, of, thrombopoietin, and, stem, cell, factor, resulted, in, an]), verbo([increase]), complemento([in, megakaryocytic, progenitors, '(', 'CFU-Mk),', whereas, erythroid, progenitors, '(', 'BFU-E)', were, decreased])]). relacion([sujeto(['Furthermore,', an]), verbo([increase]), complemento([in, cells, expressing, megakaryocytic, markers, 'CD41', and, 'CD42b', was, observed, in, 'STAT5', 'RNAi', 'cells,', as, was, an, increase, in, the, percentage, of, polyploid, cells])]). relacion([sujeto(['Reversely,', overexpression, of]), verbo([activated]), complemento(['STAT5A(1*6)', mutants, severely, impaired, megakaryocyte, development, and, induced, a, robust, erythroid, differentiation])]). relacion([sujeto(['Microarray', and, quantitative, reverse, 'transcription-polymerase', chain, reaction, analysis, revealed, changes, in, expression, of, a, number, of, 'genes,', including, 'GATA1,', which, was, downmodulated, by, 'STAT5', 'RNAi', and, upregulated, by]), verbo([activated]), complemento(['STAT5'])]). relacion([sujeto(['Absence', of, mast, cells, in, animal, models, can]), verbo([lead]), complemento([to, impairment, in, the, innate, immune, response, to, parasites, and, bacterial, infections])]). relacion([sujeto(['Understanding', mast, cell, differentiation]), verbo([provides]), complemento([important, insights, into, mechanisms, of, lineage, selection, during, hematopoiesis, and, can, provide, targets, for, new, drug, development, to, treat, mast, cell, disorders])]). relacion([sujeto(['We']), verbo([report]), complemento([a, case, of, pediatric, acute, megakaryocytic, leukemia, '(', 'AMKL)', showing, 48, ',', 'XX,+21,+21', as, a, sole, acquired, cytogenetic, abnormality, without, the, mutation, of, 'GATA1', gene])]). relacion([sujeto(['We', could, not]), verbo([find]), complemento([any, 'mutations,', including, known, 'polymorphisms,', which, are, known, to, be, involved, in, transient, myeloproliferative, disorder, and, acute, megakaryocytic, leukemia, of, 'Down', syndrome])]). relacion([sujeto(['Through', the, analysis, of, the, hematopoietic, potential, of, primitive, cord, blood, cells, in, which, 'MLLT3', expression]), verbo([has]), complemento([been, knocked, 'down,', we, identify, a, requirement, for, 'MLLT3', in, the, elaboration, of, the, erythroid, and, megakaryocytic, lineages])]). relacion([sujeto(['Conversely,', forced, expression, of, 'MLLT3']), verbo([promotes]), complemento([the, output, of, erythroid, and, megakaryocytic, 'progenitors,', and, analysis, of, 'MLLT3', mutants, suggests, that, this, capacity, of, 'MLLT3', depends, on, its, transcriptional, regulatory, activity])]). relacion([sujeto(['Gene', expression, and, 'cis-regulatory', element, analyses]), verbo([reveal]), complemento([crossregulatory, interactions, between, 'MLLT3', and, 'E/Meg-affiliated', transcription, factor, 'GATA-1'])]). relacion([sujeto(['A', hierarchical, hematopoietic, development, with, myeloid, versus, lymphoid, bifurcation]), verbo([has]), complemento([been, proposed, downstream, of, the, multipotent, progenitor, '(', 'MPP)', 'stage,', based, on, prospective, isolation, of, progenitors, capable, of, generating, only, myeloerythroid, cells, '(', common, myeloid, 'progenitor,', 'CMP)', or, only, lymphocytes, '(', common, lymphoid, 'progenitor,', 'CLP)'])]). relacion([sujeto(['Two', independent, populations]), verbo([expressing]), complemento([either, 'GATA-1', or, 'PU'])]). relacion([sujeto(['The', journeys, that, hematopoietic, cells, take, to, differentiate, from, 'long-term', stem, cells, into, committed, cells]), verbo([have]), complemento([recently, been, a, topic, of, debate])]). relacion([sujeto(['(', 2007, ')']), verbo([provide]), complemento([new, insights, into, the, paths, traveled, by, hematopoietic, progenitors])]). relacion([sujeto(['In', a, mouse, experimental, asthma, 'model,', the, administration, of, bacterial, lipopolysaccharide, '(', 'LPS),', particularly, at, low, 'doses,']), verbo([enhances]), complemento([the, levels, of, ovalbumin, '(', 'OVA)-induced', eosinophilic, airway, inflammation])]). relacion([sujeto(['In', an, effort, to, clarify, the, cellular, and, molecular, basis, for, the, 'LPS', 'effect,', we, demonstrate, that, the, 'OVA-induced', eosinophilic, inflammation, in, the, lung, is, dramatically]), verbo([increased]), complemento([by, administration, of, 'LPS', at, the, priming, phase, in, 'wild-type', 'mice,', whereas, such, an, increase, was, not, observed, in, mast, cell, deficient, mice])]). relacion([sujeto(['Adoptive', transfer, of, bone, 'marrow-derived', mast, cells, '(', 'BMMC)', from, wild, type, but, not, from, 'Toll-like', receptor, 4, '(', 'TLR4)-deficient', mice, restored, the]), verbo([increased]), complemento([eosinophilic, inflammation, in, mast, 'cell-deficient', mice])]). relacion([sujeto(['Moreover,', in, vitro, analysis, revealed, that, treatment, of, 'BMMC', with, 'LPS', resulted, in, sustained, 'up-regulation', of, 'GATA1', expression, and]), verbo([increased]), complemento([production, of, 'Th2', cytokines, '(', 'IL-4,', 'IL-5,', and, 'IL-13)', upon, restimulation])]). relacion([sujeto(['Thus,', mast, cells, appear, to, control, allergic, airway, inflammation, after, their, activation, and, modulation, through, 'TLR4-mediated', induction, of, 'GATA1', proteins, and, subsequent]), verbo([increase]), complemento([in, 'Th2', cytokine, production])]). relacion([sujeto(['Similarly,', 'Gata1', knockdown, to, 5, '%', of, its, 'wild-type', level]), verbo([causes]), complemento([high, incidence, of, erythroid, leukaemia, in, mice])]). relacion([sujeto(['The', 'GATA1-related', leukaemias, in, both, human, and, mouse, could]), verbo([provide]), complemento([important, insights, into, the, mechanism, of, 'multi-step', leukaemogenesis])]). relacion([sujeto(['This', fragment, reduced, reporter, gene, expression, in, 'K562', 'cells,', and, 'GATA-1', was, shown, to]), verbo([bind]), complemento([within, this, sequence, at, the, -, 566, 'GATA', site])]). relacion([sujeto(['Chromatin', immunoprecipitation, of, fetal, liver, tissue, from, 'beta-YAC', transgenic, mice, demonstrated, that, 'GATA-1,', 'FOG-1,', and, 'Mi2', were]), verbo([recruited]), complemento([to, the, '(', 'A)gamma-globin', -, 566, or, '(', 'G)gamma-globin', -, 567, 'GATA', site, when, 'gamma-globin', expression, was, low, '(', day, 18, ')', but, not, when, 'gamma-globin', was, expressed, '(', day, 12, ')'])]). relacion([sujeto(['These', data]), verbo([suggest]), complemento([that, during, definitive, 'erythropoiesis,', 'gamma-globin', gene, expression, is, 'silenced,', in, 'part,', by, binding, a, protein, complex, containing, 'GATA-1,', 'FOG-1,', and, 'Mi2', at, the, -, 566, /, -, 567, 'GATA', sites, of, the, proximal, 'gamma-globin', promoters])]). relacion([sujeto(['A', major, 'hurdle,', 'however,', is, to]), verbo([promote]), complemento([the, directed, and, efficient, differentiation, of, 'ES', cells, toward, a, specific, lineage])]). relacion([sujeto(['Each', of, these, factors, appears, to]), verbo([regulate]), complemento([a, step, of, the, 'process:', 'Bmp4', promotes, the, very, efficient, formation, of, 'mesoderm;', bFGF, and, activin, 'A', induce, the, differentiation, of, these, mesodermal, precursors, to, the, hemangioblast, 'fate;', and, 'VEGF', is, required, for, the, production, of, fully, committed, hematopoietic, progenitors])]). relacion([sujeto(['The', stimulation, of, mesodermal, precursors, by, bFGF, and, activin, 'A', switches, on, very, rapidly, the, hematopoietic, 'program,', allowing, us, to, dissect, the, molecular, events]), verbo([leading]), complemento([to, the, formation, of, the, hemangioblast])]). relacion([sujeto(['Interestingly,']), verbo([increased]), complemento([expression, levels, of, genes, such, as, 'cMyb,', 'Pu'])]). relacion([sujeto(['This', stepwise, control, of, differentiation, is, extremely, 'efficient,', giving, rise, to, a, very, high, frequency, of, hematopoietic, 'precursors,', and]), verbo([provides]), complemento([an, optimal, system, for, understanding, the, molecular, machineries, involved, in, blood, progenitor, commitment])]). relacion([sujeto(['Evidences', indicate, that, locus, control, region, '(', 'LCR)', of, 'beta-globin', spatially, closes, to, the, downstream, active, gene, promoter, to]), verbo([mediate]), complemento([the, transcriptional, activation, by, looping])]). relacion([sujeto(['DNA']), verbo([binding]), complemento([proteins, may, play, an, important, role, in, the, looping, formation])]). relacion([sujeto(['To', shed, light, on, whether, 'NF-E2', is]), verbo([involved]), complemento([in, this, 'process,', 'DS19MafKsiRNA', cell, pools, were, established, by, specifically, knocked, down, the, expression, of, 'MafK/NF-E2', 'p18,', one, subunit, of, 'NF-E2', heterodimer])]). relacion([sujeto(['H3', 'acetylation,', 'H3-K4', methylation, and, the, deposition, of, 'RNA', polymerase, 'II,', but, not, the, recruitment, of, 'GATA-1,', were, also]), verbo([found]), complemento([reduced, at, the, 'beta-globin', gene, cluster])]). relacion([sujeto(['Chromosome', 'Conformation', 'Capture', '(', 3, 'C)', assay, showed, that, the, 'cross-linking', frequency, between, the, main, 'NF-E2']), verbo([binding]), complemento([site, 'HS2', and, downstream, structural, genes, was, reduced, compared, to, the, normal, cell])]). relacion([sujeto(['This', result, demonstrated, that, 'MafK/NF-E2', p18, recruitment, was]), verbo([involved]), complemento([in, the, physical, proximity, of, 'LCR', and, active, 'beta-globin', genes, upon, 'beta-globin', gene, transcriptional, activation])]). relacion([sujeto(['We', used, a, gene, complementation, strategy, combined, with, microarray, screening, to, identify, miRNAs]), verbo([involved]), complemento([in, the, formation, of, erythroid, '(', red, 'blood)', cells])]). relacion([sujeto(['Two']), verbo([conserved]), complemento(['miRNAs,', miR, 144, and, miR, 451, ',', emerged, as, direct, targets, of, the, critical, hematopoietic, transcription, factor, 'GATA-1'])]). relacion([sujeto(['In', 'vivo,', 'GATA-1']), verbo([binds]), complemento([a, distal, upstream, regulatory, element, to, activate, 'RNA', polymerase, 'II-mediated', transcription, of, a, single, common, precursor, 'RNA', '(', 'pri-miRNA)', encoding, both, mature, miRNAs])]). relacion([sujeto(['These', results]), verbo([reveal]), complemento([a, miRNA, locus, that, is, required, for, erythropoiesis, and, uncover, a, new, regulatory, axis, through, which, 'GATA-1', controls, this, process])]). relacion([sujeto(['The', zinc, finger, transcription, factor, 'GATA-1']), verbo([requires]), complemento([direct, physical, interaction, with, the, cofactor, friend, of, 'GATA-1', '(', 'FOG-1)', for, its, essential, role, in, erythroid, and, megakaryocytic, development])]). relacion([sujeto(['They', also]), verbo([provide]), complemento([evidence, for, lineage, instability, during, early, stages, of, hematopoietic, lineage, commitment])]). relacion([sujeto(['The', histone, 'H3', lysine, 79, methyltransferase, 'DOT1L/KMT4', can]), verbo([promote]), complemento([an, oncogenic, pattern, of, gene, expression, through, binding, with, several, 'MLL', fusion, partners, found, in, acute, leukemia])]). relacion([sujeto(['Here', we]), verbo([report]), complemento([that, 'DOT1L', recruitment, is, ubiquitously, coupled, with, active, transcription, in, diverse, mammalian, cell, types])]). relacion([sujeto(['DOT1L', preferentially, occupies, the, proximal]), verbo([transcribed]), complemento([region, of, active, 'genes,', correlating, with, enrichment, of, 'H3K79', 'di-', and, trimethylation])]). relacion([sujeto(['ChIP-chip', tiling, arrays, revealed, that, levels, of, all, degrees, of, genic, 'H3K79', methylation, correlate, with, mRNA, abundance, and, dynamically]), verbo([respond]), complemento([to, changes, in, gene, activity])]). relacion([sujeto(['Our', findings, highlight, several, similarities, between, the, patterning, of, 'H3K4', methylation, and, that, of, 'H3K79', methylation, in, mammalian, 'chromatin,']), verbo([suggesting]), complemento([a, widespread, mechanism, for, parallel, or, sequential, recruitment, of, 'DOT1L', and, 'MLL', to, genes, in, their, normal, &, 'quot;on"', state])]). relacion([sujeto(['Twenty-four', patients, '(', 53, '%', ')', had, 'AMKL']), verbo([associated]), complemento([with, 'Down', syndrome, '(', 'DS-AMKL)', and, 21, '(', 47, '%', ')', had, 'non-DS-AMKL'])]). relacion([sujeto(['The', transcription, factor, 'Gata1', is]), verbo([expressed]), complemento([in, several, hematopoietic, lineages, and, plays, essential, roles, in, normal, hematopoietic, development, during, embryonic, stages])]). relacion([sujeto(['The', lethality, of, 'Gata1-null', embryos]), verbo([has]), complemento([precluded, determination, of, its, role, in, adult, erythropoiesis])]). relacion([sujeto(['Here', we]), verbo([have]), complemento([examined, the, effects, of, 'Gata1', loss, in, adult, erythropoiesis, using, conditional, 'Gata1', knockout, mice, expressing, either, 'interferon-', or, 'tamoxifen-inducible', 'Cre', recombinase, '(', 'Mx-Cre', and, 'Tx-Cre,', 'respectively)'])]). relacion([sujeto(['Mx-Cre-mediated', 'Gata1', 'recombination,', although, 'incomplete,', resulted, in, maturation]), verbo([arrest]), complemento([of, 'Gata1-null', erythroid, cells, at, the, proerythroblast, 'stage,', 'thrombocytopenia,', and, excessive, proliferation, of, megakaryocytes, in, the, spleen])]). relacion([sujeto(['Furthermore,', on, treatment, with, a, hemolytic, 'agent,', these, mice, failed, to]), verbo([activate]), complemento([a, stress, erythropoietic, 'response,', despite, the, rising, erythropoietin, levels])]). relacion([sujeto(['While', some, key, megakaryocytic, transcription, factors]), verbo([have]), complemento([been, 'identified,', the, complete, network, of, megakaryocytic, transcriptional, control, is, poorly, understood])]). relacion([sujeto(['This', approach, identified, 199, differentially]), verbo([expressed]), complemento([transcription, factors, or, transcriptional, regulators])]). relacion([sujeto(['Furthermore,', many, genes, with, transcription, factor, activity, or, transcription, factor]), verbo([binding]), complemento([activity, were, identified, in, megakaryocytes, that, had, not, previously, been, associated, with, that, 'lineage,', including, 'BTEB1,', 'NR4A2,', 'FOXO1A,', 'MEF2C,', 'HDAC5,', 'VDR,', and, several, genes, associated, with, the, tumor, suppressor, p53, '(', 'HIPK2,', 'FHL2,', and, 'TADA3L)'])]). relacion([sujeto(['Protein', expression, and]), verbo([nuclear]), complemento([localization, were, confirmed, in, megakaryocytic, cells, for, four, of, the, novel, candidate, megakaryocytic, transcription, 'factors:', 'FHL2,', 'MXD1,', 'E2F3,', and, 'RFX5'])]). relacion([sujeto(['In', light, of, the, hypothesis, that, transcription, factors]), verbo([expressed]), complemento([in, a, particular, differentiation, program, are, important, contributors, to, such, a, 'program,', these, data, substantially, expand, our, understanding, of, transcriptional, regulation, in, megakaryocytic, differentiation, of, stem, and, progenitor, cells])]). relacion([sujeto(['Targeted', disruption, of, the, 'Runx1/', 'AML1', gene, in, mice]), verbo([has]), complemento([demonstrated, that, it, is, required, for, the, emergence, of, definitive, hematopoietic, cells, but, that, it, is, not, essential, for, the, formation, of, primitive, erythrocytes])]). relacion([sujeto(['These', findings]), verbo([led]), complemento([to, the, conclusion, that, 'Runx1', is, a, 'stage-specific', transcription, factor, acting, only, during, definitive, hematopoiesis])]). relacion([sujeto(['However,', the, zebrafish, and, 'Xenopus', homologs, of, 'Runx1']), verbo([have]), complemento([been, shown, to, play, roles, in, primitive, 'hematopoiesis,', suggesting, that, mouse, 'Runx1', might, also, be, involved, in, the, development, of, primitive, lineages])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, mouse, 'Runx1', plays, a, role, in, the, development, of, both, primitive, and, definitive, hematopoietic, cells])]). relacion([sujeto(['A', complete, understanding, of, the, transcriptional, regulation, of, developmental, lineages]), verbo([requires]), complemento([that, all, relevant, factors, be, identified])]). relacion([sujeto(['Here,', we]), verbo([have]), complemento([taken, a, proteomic, approach, to, identify, novel, proteins, associated, with, 'GATA-1,', a, 'lineage-restricted', zinc, finger, transcription, factor, required, for, terminal, erythroid, and, megakaryocytic, maturation])]). relacion([sujeto(['We', identify, the, 'Krüppel-type', zinc, finger, transcription, factor, 'ZBP-89', as, being, a, component, of, multiprotein, complexes]), verbo([involving]), complemento(['GATA-1', and, its, essential, cofactor, 'Friend', of, 'GATA-1', '(', 'FOG-1)'])]). relacion([sujeto(['These', findings, identify, 'ZBP-89', as, being, a, novel, transcription, factor]), verbo([involved]), complemento([in, erythroid, and, megakaryocytic, development, and, suggest, that, it, serves, a, cooperative, function, with, 'GATA-1', 'and/or', 'FOG-1', in, a, developmental, 'stage-specific', manner])]). relacion([sujeto(['The', level, of, survivin, was]), verbo([reported]), complemento([to, be, scarce, in, mouse, megakaryocytes, '(', 'MKs)', compared, with, erythroid, cells])]). relacion([sujeto(['Considering', this]), verbo([finding]), complemento([and, previously, reported, in, vitro, data, showing, decreased, 'MK', ploidy, upon, 'retroviral-mediated', overexpression, of, 'survivin,', we, sought, to, examine, whether, ectopic, survivin, expression, in, the, 'MK', lineage, might, alter, ploidy, level, in, vivo])]). relacion([sujeto(['Here', we]), verbo([report]), complemento([the, generation, of, 2, tissue, specific, hematopoietic, transgenic, mouse, 'models,', one, expressing, survivin, in, both, the, erythroid, and, 'MK', lineages, and, the, other, expressing, survivin, solely, in, the, 'MK', lineage])]). relacion([sujeto(['The', specification, and, differentiation, of, hematopoietic, stem, cells, into, red, blood, cells]), verbo([requires]), complemento([precise, coordination, by, multiple, transcription, factors])]). relacion([sujeto(['Most', genes, important, for, erythroid, maturation, are]), verbo([regulated]), complemento([by, the, 'Gata', family, of, 'DNA-binding', proteins])]). relacion([sujeto(['Previously,', we, identified, three, novel, genes, 'kelch-repeat', containing, protein, '(', 'krcp),', 'kiaa0650,', and, 'testhymin/glucocorticoid', inducible, transcript, 1, '(', 'glcci1)', to, be]), verbo([expressed]), complemento([in, erythroid, cells, in, a, 'Gata-independent', 'manner,', and, we, sought, to, further, understand, how, these, transcripts, are, regulated, during, zebrafish, hematopoiesis])]). relacion([sujeto(['Upon', examination, of, embryos, deficient, for, 'Gata1,', 'Gata2,', 'Biklf,', 'and/or', 'Scl,', we]), verbo([found]), complemento([distinct, gene, combinations, were, required, for, expression, of, the, novel, genes])]). relacion([sujeto(['While', krcp, expression, was, dependent, upon, 'Gata1', and, 'Biklf,', kiaa0650, expression, was, greatly, reduced, and, glcci1, was]), verbo([maintained]), complemento([in, 'Gata1/Gata2/Biklf-deficient', embryos])]). relacion([sujeto(['As', with, the, gata1, 'gene,', kiaa0650, and, krcp]), verbo([required]), complemento(['Scl', for, blood, expression])]). relacion([sujeto(['Although', 'reduced,', glcci1, was]), verbo([expressed]), complemento([in, posterior, blood, precursors, in, the, absence, of, 'Scl', and, 'Gata2'])]). relacion([sujeto(['This', work, identifies, glcci1, as, having, 'Scl-independent', expression, in, the, posterior, hematopoietic, 'mesoderm,']), verbo([suggesting]), complemento([that, its, posterior, expression, is, activated, by, factors, upstream, or, parallel, to, 'Scl', and, 'Gata2'])]). relacion([sujeto(['Additionally,', these, studies, establish, that, blood, gene, expression, programs, are]), verbo([regulated]), complemento([by, transcription, factors, acting, in, combination, during, erythroid, maturation])]). relacion([sujeto(['Enhancers', can]), verbo([regulate]), complemento([designate, promoters, over, long, distances, by, forming, chromatin, loops])]). relacion([sujeto(['We', examined, the, chromosome, conformation, of, the, 'Kit', gene, that, is]), verbo([expressed]), complemento([during, early, erythropoiesis, but, is, downregulated, upon, cell, maturation])]). relacion([sujeto(['In', immature, 'cells,', a, distal, enhancer]), verbo([bound]), complemento([by, 'GATA-2', is, in, physical, proximity, with, the, active, 'Kit', promoter])]). relacion([sujeto(['Upon', cell, 'maturation,', 'GATA-1', displaces, 'GATA-2', and]), verbo([triggers]), complemento([a, loss, of, the, 'enhancer/promoter', interaction])]). relacion([sujeto(['Moreover,', 'GATA-1', reciprocally]), verbo([increases]), complemento([the, proximity, in, nuclear, space, among, distinct, downstream, 'GATA', elements])]). relacion([sujeto(['GATA-1-induced', transitions, in, chromatin, conformation, are, not, simply, the, consequence, of, transcription, inhibition, and]), verbo([require]), complemento([the, cofactor, 'FOG-1'])]). relacion([sujeto(['This', work, shows, that, a, 'GATA', factor, exchange, reconfigures, 'higher-order', chromatin, 'organization,', and]), verbo([suggests]), complemento([that, de, novo, chromatin, loop, formation, is, employed, by, nuclear, factors, to, specify, repressive, outcomes])]). relacion([sujeto(['In', addition, to, its, immunosuppressive, 'activity,', 'HDAC', inhibitors, block, 'GATA']), verbo([binding]), complemento(['protein-1', '(', 'GATA-1)', gene, expression, in, megakaryocytes, and, elicit, thrombocytopenia])]). relacion([sujeto(['In', this]), verbo([report]), complemento([we, state, that, for, a, given, immunosuppressive, dose, of, 'HDAC', 'inhibitor,', the, ratio, of, 'GATA-1', reporter, gene, activity, relative, to, 'IL-2', reporter, gene, assay, '(', 'G/I', ratio, of, measured, 'IC(50))', can, be, predictive, of, a, 'HDAC', 'inhibitor\'s', thrombocytopenic, effect])]). relacion([sujeto(['To', assess, whether, alterations, in, the, stromal, 'cell-derived', 'factor-1', '(', 'SDF-1)/CXCR4', occur, in, patients, with, primary, myelofibrosis, '(', 'PMF)', and, in, 'Gata1', low, 'mice,', an, animal, model, for, 'myelofibrosis,', and, whether, these, abnormalities, might, account, for]), verbo([increased]), complemento(['stem/progenitor', cell, trafficking])]). relacion([sujeto(['Furthermore,', 'SDF-1', immunostaining, of, marrow, sections, progressively]), verbo([increased]), complemento([with, age])]). relacion([sujeto(['In', 'fact,', plasma, 'SDF-1', levels, in, 'PMF', patients, were, significantly, higher, '(', by, 'twofold)', than, normal, '(', p, &, 'lt;', 0.01, ')', and, 'SDF-1', immunostaining, of, marrow, biopsy, specimens, demonstrated]), verbo([increased]), complemento(['SDF-1', deposition, in, specific, areas])]). relacion([sujeto(['Similar', to, what, already]), verbo([has]), complemento([been, reported, for, 'PMF', 'patients,', the, marrow, from, 'Gata1', low, mice, contained, fewer, 'CXCR4', pos, 'CD117', pos, cells, and, these, cells, expressed, low, levels, of, 'CXCR4', mRNA, and, protein])]). relacion([sujeto(['We']), verbo([suggest]), complemento([that, these, abnormalities, contribute, to, the, increased, 'stem/progenitor', cell, trafficking, observed, in, this, mouse, model, as, well, as, patients, with, 'PMF'])]). relacion([sujeto(['Multiple', putative, transcription, factor]), verbo([binding]), complemento([sites, were, identified, in, the, promoter, from, the, -, 860, to, the, -, 1, base, pair, '(', 'bp)'])]). relacion([sujeto(['A', region, between, -, 221, and, -, 128, bp]), verbo([retains]), complemento([most, of, the, transcriptional, activity, of, the, 'full-length', promoter])]). relacion([sujeto(['In', vitro, experiments, of, electrophoretic, mobility, shifts, and, in, vivo, studies, using, chromatin, 'immuno-precipitation', '(', 'ChIP)', assays, show, that, the, 'Sp1/Sp3', proteins]), verbo([bind]), complemento([the, 'CACCC', site, in, the, nuclei, of, 'K562', cells])]). relacion([sujeto(['Co-transfection', of, 'Sp1', expression, plasmids, and, plasmids, with, a, 'wild-type', promoter, showed]), verbo([enhanced]), complemento([reporter, gene, activity, in, a, 'dose-dependent', manner])]). relacion([sujeto(['The', combined, data, demonstrate, that, 'Sp1/Sp3,', but, not, 'EKLF,', is]), verbo([involved]), complemento([in, the, activation, of, the, 'GATA-1', erythroid, 'promoter,', and, that, histones, 'H3', and, 'H4', are, highly, acetylated, in, this, promoter, region, for, an, actively, transcribed, 'GATA-1', gene, in, 'K562', cells, in, which, 'EKLF', is, barely, detectable])]). relacion([sujeto(['This', gene, encodes, protoporphyrinogen, 'oxidase,', which, is]), verbo([involved]), complemento([in, synthesizing, heme, for, red, blood, cells, and, heme, as, a, cofactor, for, the, respiratory, cytochromes])]). relacion([sujeto(['In', vitro, luciferase, transfection, assays, in, human, uninduced, and, hemin]), verbo([induced]), complemento([erythroleukemic, 'K562', cells, showed, that, the, presence, of, exon, 1, increased, promoter, activity, fourfold, as, compared, to, reporter, constructs, lacking, this, exon])]). relacion([sujeto(['This', transcriptional, regulation, was]), verbo([mediated]), complemento([by, two, 'GATA-1', sites, in, exon, 1])]). relacion([sujeto(['Electrophoretic', mobility, shift, and, chromatin, immunoprecipitation, assays, demonstrated, that, both, 'GATA', sites, were, able, to]), verbo([bind]), complemento(['GATA-1', in, vitro, and, in, vivo])]). relacion([sujeto(['Exon', 1, did, not, affect, promoter, activity, in, human, hepatoma, 'HepG2', cells, and, 'U937', monocytic, cells, but, its, presence]), verbo([decreased]), complemento([promoter, activity, in, 'HeLa', human, cervical, carcinoma, cells])]). relacion([sujeto(['We', conclude, that, the, 'GATA-1']), verbo([binding]), complemento([sites, in, exon, 1, constitute, key, regulatory, elements, in, differential, expression, of, 'PPOX', in, erythroid, and, 'non-erythroid', cells])]). relacion([sujeto(['Most', bilaterian, animals]), verbo([have]), complemento([evolved, a, through, gut, that, is, regionally, specialized, along, the, 'anterior-posterior', axis])]). relacion([sujeto(['Members', of, the, 'Fox', and, 'GATA', families, of, transcription, factors]), verbo([have]), complemento([conserved, functions, in, patterning, ectodermal, and, endodermal, gut, components])]). relacion([sujeto(['We']), verbo([have]), complemento([isolated, and, characterized, expression, of, one, 'FoxA', gene, '(', 'CapI-foxA)', and, four, 'GATA', genes, '(', 'CapI-gataB1,', 'CapI-gataB2,', 'CapI-gataB3,', and, 'CapI-gataA1)', from, 'Capitella', sp])]). relacion([sujeto(['Both', gene, families, are]), verbo([expressed]), complemento([in, the, developing, gut, of, this, polychaete])]). relacion([sujeto(['CapI-foxA,', an, ortholog, of, the, 'FoxA', 'subgroup,', is]), verbo([expressed]), complemento([in, vegetal, hemisphere, micromeres, of, 'cleavage-stage', 'embryos,', in, multiple, blastomeres, within, and, surrounding, the, blastopore, during, 'gastrulation,', and, throughout, morphogenesis, of, the, 'pharynx,', 'esophagus,', and, hindgut])]). relacion([sujeto(['The', 'CapI-gataB', genes, group, within, the, vertebrate, 'GATA4/5/6', 'subfamily,', appear, to, be, products, of, 'lineage-specific', gene, 'duplication,', and, are]), verbo([expressed]), complemento([in, specific, domains, of, endomesoderm])]). relacion([sujeto(['CapI-gataB1', is]), verbo([expressed]), complemento([in, endoderm, precursors, and, throughout, developing, midgut, 'endoderm,', and, is, particularly, prominent, at, anterior, and, posterior, midgut, boundaries])]). relacion([sujeto(['CapI-gataB2', is, 'co-expressed', with, 'CapI-gataB1', in, midgut, 'endoderm,', and, is, also]), verbo([expressed]), complemento([in, visceral, mesoderm])]). relacion([sujeto(['CapI-gataA1', groups, within, the, vertebrate, 'GATA1/2/3', subfamily, and, is]), verbo([expressed]), complemento([primarily, in, ectodermal, tissues, of, the, 'brain,', ventral, nerve, 'cord,', lateral, 'trunk,', and, both, pharyngeal, and, esophageal, regions, of, the, foregut])]). relacion([sujeto(['AML1-ETO', is, one, of, the, most, common, chromosomal, translocation, products]), verbo([associated]), complemento([with, acute, myelogenous, leukemia, '(', 'AML)'])]). relacion([sujeto(['Induced', 'AML1-ETO', expression, in, embryonic, zebrafish]), verbo([causes]), complemento([a, phenotype, that, recapitulates, some, aspects, of, human, 'AML'])]). relacion([sujeto(['This', fate, change, is, characterized, by, a]), verbo([loss]), complemento([of, gata1, expression, and, an, increase, in, pu])]). relacion([sujeto(['These', results, demonstrate, that, scl, is, an, important, mediator, of, the, ability, of, 'AML1-ETO', to, reprogram, hematopoietic, cell, fate, 'decisions,']), verbo([suggesting]), complemento([that, scl, may, be, an, important, contributor, to, 'AML1-ETO-associated', leukemia])]). relacion([sujeto(['In', 'addition,', treatment, of, 'AML1-ETO', transgenic, zebrafish, embryos, with, a, histone, deacetylase, 'inhibitor,', 'Trichostatin', 'A,', restores, scl, and, gata1, 'expression,', and, ameliorates, the, accumulation, of, granulocytic, cells]), verbo([caused]), complemento([by, 'AML1-ETO'])]). relacion([sujeto(['Studies', with, 'GATA', factor, mutants, and, novel, chimeric, 'GATA', factors]), verbo([provided]), complemento([evidence, that, both, 'GATA-1', and, 'GATA-2', have, highly, unstable, zinc, finger, core, modules])]). relacion([sujeto(['The', 'GATA-1', and, 'GATA-2', 'N-termini', both]), verbo([confer]), complemento([stabilization, to, their, respective, zinc, finger, core, modules])]). relacion([sujeto(['In', 'contrast,', the, 'GATA-1', and, 'GATA-2', 'C-termini']), verbo([confer]), complemento([stabilization, and, 'destabilization,', respectively])]). relacion([sujeto(['As', 'GATA-2', stabilization, via, proteasome, inhibition, impairs, the, capacity, of, 'GATA-1', to, displace, 'GATA-2', from, endogenous, chromatin, 'sites,', we, propose, that, differential, 'GATA', factor, stability, is, an, important, determinant, of, chromatin]), verbo([target]), complemento([site, occupancy, and, therefore, the, establishment, of, genetic, networks, that, control, hematopoiesis])]). relacion([sujeto(['Acute', myeloid, leukemia, '(', 'AML)', in, 'Down', syndrome, '(', 'DS)', children]), verbo([has]), complemento([several, unique, features, including, a, predominance, of, the, acute, megakaryocytic, leukemia, '(', 'AMkL)', 'phenotype,', higher, 'event-free', survivals, compared, to, 'non-DS', children, using, cytosine, arabinoside, '(', 'ara-C)/anthracycline-based', protocols, and, a, uniform, presence, of, somatic, mutations, in, the, 'X-linked', transcription, factor, 'gene,', 'GATA1'])]). relacion([sujeto(['In', the, 'K562pTet-on/ETS2', 'cells,', 'ETS2', induction]), verbo([conferred]), complemento([differences, in, sensitivities, to, 'ara-C', and, 'daunorubicin,', depending, on, 'GATA1', levels])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, 'ETS2', expression, is, linked, to, the, biology, of, 'AMkL', in, both, 'DS', and, 'non-DS', 'children,', and, that, 'ETS2', acts, by, regulating, expression, of, hematopoietic, lineage, and, transcription, factor, genes, involved, in, erythropoiesis, and, 'megakaryopoiesis,', and, in, chemotherapy, sensitivities])]). relacion([sujeto(['Long-range', interactions, between, distant, regulatory, 'elements,', such, as, 'enhancers,', and, their]), verbo([target]), complemento([genes, underlie, the, specificity, of, gene, expression, in, many, developmentally, regulated, gene, families])]). relacion([sujeto(['NLI/Ldb1,', a, widely]), verbo([expressed]), complemento([nuclear, 'factor,', is, a, potential, mediator, of, 'long-range', interactions])]). relacion([sujeto(['Here,', we, show, that, 'NLI/Ldb1', and, 'erythroid-binding', partners, 'GATA-1/SCL/LMO2']), verbo([bind]), complemento([in, vivo, to, the, 'beta-globin', locus, control, region, '(', 'LCR)'])]). relacion([sujeto(['The', 'C-terminal', 'LIM', interaction, domain, of, 'NLI', is]), verbo([required]), complemento([for, formation, of, the, complex, on, chromatin])]). relacion([sujeto(['Loss', of, the, 'LIM', domain, converts, 'NLI', into, a, 'dominant-negative', inhibitor, of, globin, gene, 'expression,', and, knockdown, of, 'NLI', by, using, shRNA, results, in, failure, to]), verbo([activate]), complemento(['beta-globin', expression])]). relacion([sujeto(['Kinetic', studies]), verbo([reveal]), complemento([that, the, 'NLI/GATA-1/SCL/LMO2', complex, is, detected, at, the, 'beta-globin', promoter, coincident, with, 'RNA', 'Pol', 'II', 'recruitment,', 'beta-globin', 'transcription,', and, chromatin, loop, formation, during, erythroid, 'differentiation,', providing, evidence, that, 'NLI', facilitates, 'long-range', gene, activation])]). relacion([sujeto(['To']), verbo([find]), complemento([out, how, 'GATA-1', and, 'GATA-2', behave, in, the, bone, marrow, of, patients, with, 'Monge\'s', disease])]). relacion([sujeto(['(', 1, ')', 'All', patients, and, controls]), verbo([expressed]), complemento(['GATA-1', mRNA, '(', 'Monge\'s', disease, 1.033, +, /, -, 0.146, ',', 'Control', 0.458, +, /, -, 0.076, ')', and, 'GATA-2', mRNA, '(', 'Monge\'s', disease, 0.451, +, /, -, 0.073, ',', 'Control', 0.185, +, /, -, 0.074, ')'])]). relacion([sujeto(['All', patients]), verbo([expressed]), complemento([both, 'GATA-1', '(', positive, cell, counts, 77.3, +, /, -, 33.3, ',', positive, score, 135.4, +, /, -, 75.4, ')', and, 'GATA-2', '(', positive, cell, counts, 29.4, +, /, -, 11.4, ',', positive, score, 48.4, +, /, -, 19.7, ')'])]). relacion([sujeto(['All', the, controls]), verbo([expressed]), complemento(['GATA-1', '(', positive, cell, counts, 18.1, +, /, -, 11.3, ',', positive, score, 24.2, +, /, -, 13.4, ')', while, 12, of, 20, controls, expressed, 'GATA-2', '(', positive, cell, counts, 5.4, +, /, -, 3.0, ',', positive, score, 7.3, +, /, -, 4.2, ')'])]). relacion([sujeto(['Two', of, inherent, 'genes,', 'GATA-1', and, 'GATA-2', which, were]), verbo([expressed]), complemento([at, higher, levels, in, patients, with, 'Monge\'s', disease, than, in, controls, might, play, significant, roles, in, the, pathogenesis, of, 'Monge\'s', disease])]). relacion([sujeto(['Available', data]), verbo([suggest]), complemento([that, gene, regulation, by, the, 'Gata-1', 'Hematopoietic', 'Regulatory', 'Domain', '(', 'Gata-1-HRD)', is, limited, to, cells, derived, from, the, erythroid, lineage])]). relacion([sujeto(['To', characterize, the, specificity, of, 'Gata-1', 'HRD', regulation, of, 'cre,', transgenic, mice]), verbo([expressing]), complemento([improved, cre, recombinase, '(', 'iCre)', under, the, control, of, 'Gata-1-HRD', were, generated])]). relacion([sujeto(['The', founders, were, crossbred, with, mice, that]), verbo([have]), complemento([an, inactive, 'loxP-containing', 'beta-galactosidase', gene, that, can, be, rescued, by, the, cre, recombinase])]). relacion([sujeto(['To', identify, the, cre]), verbo([expressing]), complemento([cells, in, 'marrow,', 'double-immunostaining', of, marrow, sections, with, 'anti-beta-galactosidase,', and, antibodies, against, various, hematopoietic, lineage, markers, or, erythropoietin, receptor, '(', 'epor)', was, performed])]). relacion([sujeto(['The', epor, positive, cells, in, marrow]), verbo([expressed]), complemento(['beta-galactosidase,', but, megakaryocytic, precursors, and, nonerythroid, 'epor-positive', cells, in, brain, and, spleen, did, not])]). relacion([sujeto(['The', prognosis, of, leukemia, developed, in, 'Down', syndrome, '(', 'DS)', patients]), verbo([has]), complemento([improved, markedly])]). relacion([sujeto(['Mutations', in, the, 'GATA1', gene]), verbo([have]), complemento([been, found, in, almost, all, 'DS', patients, with, 'AMKL'])]). relacion([sujeto(['In', 'contrast,', it]), verbo([has]), complemento([been, shown, that, occurrence, of, 'DS', acute, myeloid, leukemia, '(', 'DS-AML)', after, 3, years, of, age, may, indicate, a, higher, risk, for, a, poor, 'prognosis,', but, its, frequency, is, very, low])]). relacion([sujeto(['The', prognostic, factor, of, gene, alterations]), verbo([has]), complemento([not, been, reported, in, older, 'DS-AML', patients])]). relacion([sujeto(['The', patient]), verbo([has]), complemento([lived, for, more, than, 5, years, after, treatment, on, the, 'AML99-Down', protocol, in, 'Japan'])]). relacion([sujeto(['This']), verbo([suggests]), complemento([that, a, patient, lacking, these, genes, alterations, might, belong, to, a, subgroup, of, older, 'DS-AML', patients, with, good, prognosis])]). relacion([sujeto(['Friend', of, 'GATA-1', '(', 'FOG-1)', is, a]), verbo([binding]), complemento([partner, of, 'GATA-1,', a, zinc, finger, transcription, factor, with, crucial, roles, in, 'erythroid,', 'megakaryocytic,', and, 'mast-cell', differentiation])]). relacion([sujeto(['FOG-1', is, indispensable, for, the, function, of, 'GATA-1', during, 'erythro/megakaryopoiesis,', but, 'FOG-1', is, not]), verbo([expressed]), complemento([in, mast, cells])]). relacion([sujeto(['Expression', of, 'FOG-1', during, the, progenitor, period]), verbo([inhibited]), complemento([the, differentiation, of, mast, cells, and, enhanced, the, differentiation, of, neutrophils])]). relacion([sujeto([1, ',', a, transcription, factor, that, positively, or, negatively, cooperates, with, 'GATA-1,', revealed, that, this, lineage, skewing, was]), verbo([caused]), complemento([by, disrupted, binding, between, 'GATA-1', and, 'PU'])]). relacion([sujeto(['However,', 'FOG-1', expression, in, mature, mast, cells, brought, approximately, a, reversible]), verbo([loss]), complemento([of, the, 'mast-cell', phenotype])]). relacion([sujeto(['In', contrast, to, the, lineage, 'skewing,', the]), verbo([loss]), complemento([of, the, 'mast-cell', phenotype, was, caused, by, 'down-regulation', of, 'MITF,', a, basic, 'helix-loop-helix', transcription, factor, required, for, 'mast-cell', differentiation, and, maturation])]). relacion([sujeto(['These', results, indicate, that, 'FOG-1']), verbo([inhibits]), complemento(['mast-cell', differentiation, in, a, differentiation, 'stage-dependent', 'manner,', and, its, effects, are, produced, via, different, molecular, mechanisms])]). relacion([sujeto(['Thrombocytosis', is]), verbo([associated]), complemento([with, 'inflammation,', and, certain, inflammatory, 'cytokines,', including, 'IFN-gamma,', stimulate, megakaryocyte, and, platelet, production])]). relacion([sujeto(['We', previously]), verbo([reported]), complemento([that, 'STAT1', expression, was, significantly, downregulated, in, 'Gata1-knockdown', murine, 'megakaryocytes,', which, also, have, impaired, terminal, maturation])]). relacion([sujeto(['Here,', we, show, that, ectopic, expression, of, 'STAT1,', or, its]), verbo([target]), complemento([effector, 'IRF-1,', rescued, multiple, defects, in, 'Gata1-deficient', megakaryopoiesis, in, 'mice,', inducing, polyploidization, and, expression, of, a, subset, of, 'platelet-expressing', genes])]). relacion([sujeto(['Enforced', expression, of, 'STAT1,', 'IRF-1,', or, 'GATA-1']), verbo([enhanced]), complemento([phosphorylation, of, 'STAT1,', 'STAT3,', and, 'STAT5', in, cultured, 'Gata1-deficient', murine, 'megakaryocytes,', with, concomitant, megakaryocyte, maturation])]). relacion([sujeto(['In', 'contrast,']), verbo([enhanced]), complemento([thrombopoietin, 'signaling,', conferred, by, enforced, expression, of, constitutively, active, 'JAK2', or, 'c-MPL,', induced, phosphorylation, of, 'STAT3', and, 'STAT5,', but, not, 'STAT1,', and, failed, to, rescue, megakaryocyte, maturation])]). relacion([sujeto(['Together,', these, findings]), verbo([reveal]), complemento([a, unique, role, for, 'STAT1', in, megakaryopoiesis, and, provide, new, insights, into, how, 'GATA-1', regulates, this, process])]). relacion([sujeto(['Our', studies, elucidate, potential, mechanisms, by, which, various, inflammatory, disorders, can]), verbo([cause]), complemento([elevated, platelet, counts])]). relacion([sujeto(['Previous', investigations, from, our, laboratory]), verbo([have]), complemento([characterized, the, ultrastructural, and, cytochemical, pathology, of, platelets, in, male, members, of, a, family, with, 'X-linked', 'GATA-1', 'G208S', macrothrombocytoenia])]). relacion([sujeto(['The', present, study]), verbo([has]), complemento([examined, one, obligate, and, three, potential, female, carriers, in, this, family])]). relacion([sujeto(['The', ability, of, their, platelets, to]), verbo([bind]), complemento([multimers, of, 'vWF,', in, contrast, to, male, family, 'members,', did, not, differ, from, normal, controls])]). relacion([sujeto(['Near', normal, as, well, as, normal, platelet, counts, and, the, ability, of, their, platelets, to]), verbo([bind]), complemento([vWF, multimers, may, protect, them, from, the, serious, bleeding, problems, of, males, with, the, 'X-linked', 'GATA-1', 'G208S', mutation])]). relacion([sujeto(['Megakaryocytes', and, platelets]), verbo([express]), complemento([the, 'Gs-coupled', 'VPAC1', 'receptor,', for, which, the, pituitary, adenylyl, 'cyclase-activating', peptide, '(', 'PACAP)', and, the, vasointestinal, peptide, '(', 'VIP)', are, agonists])]). relacion([sujeto(['A', total, of, 2, patients, with, trisomy, 18, p, with, 'PACAP', overexpression, and, transgenic, mice, overexpressing, 'PACAP', in, megakaryocytes]), verbo([have]), complemento(['thrombopathy,', a, mild, 'thrombocytopenia,', and, a, reduced, number, of, mature, megakaryocytes, in, their, bone, marrow])]). relacion([sujeto(['The', addition, of, 'PACAP,', 'VIP,', or, the, adenylyl, cyclase, activator, forskolin, to, 'CD34(+)', cells]), verbo([inhibits]), complemento([megakaryocyte, differentiation])]). relacion([sujeto(['In', 'contrast,', neutralizing, monoclonal, 'anti-PACAP', '(', 'PP1A4)', or, 'anti-VPAC1', '(', 23, 'A11)', antibodies]), verbo([inhibit]), complemento([cAMP, formation, and, stimulate, megakaryopoiesis, in, a, 'thrombopoietin-independent', manner])]). relacion([sujeto(['Moreover,', 'wild-type', mice, obtain, an]), verbo([increased]), complemento([platelet, count, after, subcutaneous, injection, of, 'PP1A4', or, 23, 'A11'])]). relacion([sujeto(['Furthermore,', 23, 'A11']), verbo([stimulates]), complemento([the, in, vitro, megakaryocyte, differentiation, of, both, normal, and, 'GATA1-deficient', human, 'CD34(+)', cells])]). relacion([sujeto(['Together,', our, data, strongly]), verbo([suggest]), complemento([that, 'VPAC1', signaling, tempers, normal, 'megakaryopoiesis,', and, that, inhibition, of, this, pathway, stimulates, megakaryocyte, 'differentiation,', enhancing, platelet, recovery, after, myelosuppressive, therapy, and, in, 'GATA1', deficiency])]). relacion([sujeto(['Surprisingly,', the, majority, of, the, excessive, numbers, of, mast, cell, progenitors, in, chimeric, 'GATA-1(Plt13/+)', mice, were]), verbo([transcribing]), complemento([the, inactive, 'Plt13', allele, of, 'GATA-1,', suggesting, that, 'GATA-1', normally, acts, to, restrict, the, emergence, of, committed, mast, cell, progenitors])]). relacion([sujeto(['In', sharp, 'contrast,', all, eosinophil, progenitors, in, these, mice, were]), verbo([transcribing]), complemento([the, normal, 'GATA-1', allele])]). relacion([sujeto(['No', excess, tissue, mast, cells, were, observed, in, 'GATA-1(Plt13/+)', 'mice,']), verbo([suggesting]), complemento([that, the, excess, mast, cell, progenitors, in, these, mice, might, be, generating, mast, cells, with, a, defective, in, vivo, proliferative, or, tissue, homing, capacity])]). relacion([sujeto(['Children', with, 'Down', syndrome, '(', 'DS)']), verbo([have]), complemento([an, approximately, 20, -, fold, higher, incidence, of, leukemia, than, unaffected, 'children,', and, most, leukemia, cases, with, 'DS', present, as, acute, megakaryocytic, leukemia, '(', 'AMKL)'])]). relacion([sujeto(['We', describe, a, child, with, 'DS', who, developed, 'TMD', followed, by, 'AMKL', and]), verbo([have]), complemento([identified, different, mutations, in, the, 'GATA1', gene, during, the, course, of, 'TMD', and, 'AMKL'])]). relacion([sujeto(['Distinct', clones, were]), verbo([associated]), complemento([with, the, development, of, 'TMD', and, 'AMKL', in, this, patient])]). relacion([sujeto(['We']), verbo([found]), complemento([a, characteristic, and, 'erythrocyte-specific', structure, between, the, previously, defined, silencer, and, the, 'enhancer,', defined, by, two, nuclease, hypersensitive, 'sites,', which, appear, when, the, enhancer, is, active, during, erythroid, differentiation])]). relacion([sujeto(['We', detected, a, progressive, enrichment, of, histone, acetylation, on, critical, enhancer]), verbo([nuclear]), complemento([factor, binding, 'sites,', in, correlation, with, the, formation, of, an, apparent, 'nucleosome-free', region])]). relacion([sujeto(['On', the, basis, of, these, 'results,', we, propose, that, the, local, chromatin, structure, of, the, chicken, 'alpha-globin', enhancer, plays, a, central, role, in, its, capacity, to, differentially]), verbo([regulate]), complemento(['alpha-globin', gene, expression, during, erythroid, differentiation, and, development])]). relacion([sujeto(['When', the, orphan]), verbo([nuclear]), complemento([receptors, 'TR2', and, 'TR4,', the, 'DNA-binding', subunits, of, the, 'DRED', repressor, 'complex,', are, forcibly, expressed, in, erythroid, cells, of, transgenic, 'mice,', embryos, exhibit, a, transient, 'mid-gestational', anemia, as, a, consequence, of, a, reduction, in, the, number, of, primitive, erythroid, cells])]). relacion([sujeto(['GATA-1', mRNA, is, specifically, diminished, in, the, erythroid, cells, of, these, 'TR2/TR4', transgenic, embryos, as, it, is, in, human, 'CD34(+)', progenitor, cells, transfected, with, forcibly]), verbo([expressed]), complemento(['TR2/TR4'])]). relacion([sujeto(['An', evolutionarily]), verbo([conserved]), complemento([direct, repeat, '(', 'DR)', 'element,', a, canonical, binding, site, for, nuclear, 'receptors,', was, identified, in, the, 'GATA1', hematopoietic, enhancer, '(', 'G1HE),', and, 'TR2/TR4', binds, to, that, site, in, vitro, and, in, vivo])]). relacion([sujeto(['Mutation', of, that, 'DR', element]), verbo([led]), complemento([to, elevated, 'Gata1', promoter, 'activity,', and, reduced, promoter, responsiveness, to, cotransfected, 'TR2/TR4'])]). relacion([sujeto(['Thus,', 'TR2/TR4', directly, represses, 'Gata1/GATA1', transcription, in, murine, and, human, erythroid, progenitor, cells, through, an, evolutionarily]), verbo([conserved]), complemento([binding, site, within, a, 'well-characterized,', 'tissue-specific', 'Gata1', 'enhancer,', thereby, providing, a, mechanism, by, which, 'Gata1', can, be, directly, silenced, during, terminal, erythroid, maturation])]). relacion([sujeto(['It', is, known, that, the, adhesion, molecule, 'ALCAM', '(', 'CD166)']), verbo([mediates]), complemento([metastasis, of, malignant, cells, and, organogenesis, in, embryos])]). relacion([sujeto([5, ')', murine, yolk, sac, cells]), verbo([express]), complemento(['ALCAM', protein, and, that, 'ALCAM', expression, can, be, used, to, define, endothelial, and, cardiac, precursors, from, hematopoietic, precursors, in, 'E8'])]). relacion([sujeto([5, ',', and, the, endothelial, marker, 'VE-cadherin', are]), verbo([expressed]), complemento([in, the, 'ALCAM', 'high+', 'fraction,', whereas, the, hematopoietic, marker, 'GATA1', and, 'Runx1', are, expressed, in, the, 'ALCAM', 'low+/-', fraction])]). relacion([sujeto(['Altogether,', these, results, indicate, that, cells]), verbo([retaining]), complemento([a, potential, to, differentiate, to, the, cardiac, lineage, are, present, in, 'E8'])]). relacion([sujeto(['Our']), verbo([report]), complemento([provides, novel, insights, into, the, origin, and, differentiation, process, of, cardiac, cells, in, the, formation, of, the, circulatory, system])]). relacion([sujeto(['In', 'zebrafish,', like, other, 'vertebrates,', hematopoietic, development]), verbo([has]), complemento([been, roughly, divided, into, two, 'waves,', termed, primitive, and, definitive])]). relacion([sujeto(['Based', on, previous, gene, expression, 'studies,', definitive, hematopoiesis]), verbo([has]), complemento([been, suggested, to, begin, with, the, generation, of, presumptive, hematopoietic, stem, cells, '(', 'HSCs)', along, the, dorsal, aorta, that, express, 'c-myb', and, runx1])]). relacion([sujeto(['EMPs', isolated, by, coexpression, of, fluorescent, transgenes, driven, by, the, lmo2, and, gata1, promoters, exhibit, an, 'immature,', blastic, morphology, and]), verbo([express]), complemento([only, erythroid, and, myeloid, genes])]). relacion([sujeto(['Additional', fate, mapping, of, mesodermal, derivatives, in, 'mid-somitogenesis', embryos]), verbo([suggests]), complemento([that, 'EMPs', are, born, directly, in, the, 'PBI'])]). relacion([sujeto(['These', studies]), verbo([provide]), complemento([phenotypic, and, functional, analyses, of, the, first, hematopoietic, progenitors, in, the, zebrafish, embryo, and, demonstrate, that, definitive, hematopoiesis, proceeds, through, two, distinct, waves, during, embryonic, development])]). relacion([sujeto(['Children', with, 'Down', syndrome, '(', 'DS)']), verbo([have]), complemento([a, 10, -, to, 20, -, fold, increased, risk, of, developing, acute, leukemia])]). relacion([sujeto(['Administration', of, prohibited, substances, to]), verbo([enhance]), complemento([athletic, performance, represents, an, emerging, 'medical,', 'social,', ethical, and, legal, issue])]). relacion([sujeto(['Some', candidate, genes, were]), verbo([found]), complemento([significantly, and, consistently, modulated, by, treatments])]). relacion([sujeto(['Ikaros--a', factor, that, positively, or, negatively, controls, gene, 'transcription--is', active, in, murine, adult, erythroid, 'cells,', and]), verbo([involved]), complemento([in, fetal, to, adult, globin, switching])]). relacion([sujeto(['Mice', with, 'Ikaros', mutations]), verbo([have]), complemento([defects, in, erythropoiesis, and, anemia])]). relacion([sujeto(['In', this, 'paper,', we]), verbo([have]), complemento([studied, the, role, of, 'Ikaros', in, human, erythroid, development, for, the, first, time])]). relacion([sujeto(['Using', a, 'gene-transfer', 'strategy,', we]), verbo([expressed]), complemento(['Ikaros', 6, '(', 'Ik6)--a', known, 'dominant--negative', protein, that, interferes, with, normal, 'Ikaros', 'activity-in', cord, blood, or, apheresis, 'CD34(+)', cells, that, were, induced, to, differentiate, along, the, erythroid, pathway])]). relacion([sujeto(['Lentivirally']), verbo([induced]), complemento(['Ik6-forced', expression, resulted, in, increased, cell, 'death,', decreased, cell, 'proliferation,', and, decreased, expression, of, 'erythroid-specific', 'genes,', including, 'GATA1', and, fetal, and, adult, globins])]). relacion([sujeto(['In', 'contrast,', we, observed, the, maintenance, of, a, residual, myeloid, population, that, can, be, detected, in, this, culture, 'system,', with, a, relative]), verbo([increase]), complemento([of, myeloid, gene, 'expression,', including, 'PU1'])]). relacion([sujeto(['In', secondary, 'cultures,', expression, of, 'Ik6', favored, reversion, of, sorted, and, phenotypically, defined, erythroid, cells, into, myeloid, 'cells,', and]), verbo([prevented]), complemento([reversion, of, myeloid, cells, into, erythroid, cells])]). relacion([sujeto(['We', conclude, that, 'Ikaros', is]), verbo([involved]), complemento([in, human, adult, or, fetal, erythroid, differentiation, as, well, as, in, the, commitment, between, erythroid, and, myeloid, cells])]). relacion([sujeto(['Since', only, 20, to, 30, '%', cells, incubated, with, 'ATRA', became, positive, for, 'CCR3,', 'CCR3(+)', population, was, enriched, by, a, magnetic]), verbo([activated]), complemento([cell, sorter, '(', 'MACS)'])]). relacion([sujeto(['Finally,', 'ATRA-induced', differentiation, and, 'eotaxin-2/CCL24', production, were, greatly]), verbo([enhanced]), complemento([in, the, 'GATA-1-overexpressed', clones])]). relacion([sujeto(['We']), verbo([report]), complemento([a, new, case, of, transient, myeloproliferative, disorder, '(', 'TMD)', in, a, non, 'Down', syndrome, neonate])]). relacion([sujeto(['A', survey, by, periodic, cytological, examinations, of, peripheral, blood, cells, and, 'GATA1', mutation, analysis, was, instituted, since, three, years, and]), verbo([has]), complemento([not, detected, up, to, date, acute, leukaemia])]). relacion([sujeto(['The', 'Entamoeba', histolytica, 'EhrabB', gene, encodes, for, a, 'Rab', 'GTPase']), verbo([involved]), complemento([in, phagocytosis])]). relacion([sujeto(['It', is, located, at, a, virulence, locus, where, the, 'Ehcp112', gene, is, in, the, complementary, strand, at, 332, bp, of, 'EhrabB', start, 'codon,']), verbo([suggesting]), complemento([a, finely, regulated, transcription, of, both, genes])]). relacion([sujeto(['It', also]), verbo([has]), complemento([sequences, with, homology, to, 'C/EBP', and, 'GATA1', binding, 'sites,', and, heat, shock, elements, '(', 'HSE)'])]). relacion([sujeto(['Primer', extension, experiments, revealed, that, 'EhrabB']), verbo([has]), complemento([at, least, four, transcription, initiation, sites])]). relacion([sujeto(['EhrabB', transcription, is, negatively]), verbo([regulated]), complemento([by, a, sequence, located, between, positions, -, 491, to, -, 428, with, respect, to, the, first, transcription, initiation, site])]). relacion([sujeto(['We', also, showed, that, the, 'URE1-like', motif]), verbo([activates]), complemento(['EhrabB', transcription])]). relacion([sujeto(['In', 'addition,', heat, shock]), verbo([activated]), complemento([the, 'EhrabB', promoter, in, episomal, constructs, and, lead, to, an, increase, in, de, novo, 'EhrabB', transcription])]). relacion([sujeto(['The', data]), verbo([suggest]), complemento([that, 'EhrabB', transcription, is, controlled, negatively, by, an, unidentified, 'sequence,', but, it, is, activated, by, an, 'URE1-like', motif])]). relacion([sujeto(['The', fusion, gene, combines, sequences, encoding, a, strong, transactivating, domain, from, the, 'EWS', protein, with, the, 'DNA']), verbo([binding]), complemento([domain, of, 'FLI-1,', an, 'ETS', transcription, factor])]). relacion([sujeto(['A', related, 'fusion,', 'TLS/ERG,']), verbo([has]), complemento([been, found, in, myeloid, leukemia])]). relacion([sujeto(['When', crossed, with, 'Mx1-cre', 'mice,', 'Cre-mediated', activation, of, 'EWS/FLI-1', resulted, in, the, rapid, development, of, 'myeloid/erythroid', leukemia, characterized, by, expansion, of, primitive, mononuclear, cells]), verbo([causing]), complemento(['hepatomegaly,', 'splenomegaly,', severe, 'anemia,', and, death])]). relacion([sujeto(['Gene', expression, profiles, of, primary, and, transplanted, animals, were, highly, 'similar,']), verbo([suggesting]), complemento([that, activation, of, 'EWS/FLI-1', was, the, primary, event, leading, to, disease, in, this, model])]). relacion([sujeto(['The', 'Cre-inducible', 'EWS/FLI-1', mouse]), verbo([provides]), complemento([a, novel, model, system, to, study, the, contribution, of, this, oncogene, to, malignant, disease, in, vivo])]). relacion([sujeto(['As', more, mammalian, 'P450', crystal, structures]), verbo([have]), complemento(['emerged,', computational, modeling, has, become, a, major, tool, to, predict, drug, metabolism, and, interactions])]). relacion([sujeto(['Using', isothermal, titration, calorimetry, '(', 'ITC)', we, successfully, evaluated, the, conformational, flexibility, of, 'P450', 2, 'B4', in]), verbo([binding]), complemento([imidazole, inhibitors, of, different, size, and, chemistry, and, dissected, the, stoichiometry, and, energetics, of, ligand, binding, allostery, in, 'P450eryF'])]). relacion([sujeto(['A', previous, investigation, detailed, the, pathology, of, platelets, in, a, family, with, the, 'X-linked', 'GATA-1', 'G208S', mutation]), verbo([causing]), complemento([dyserythropoiesis, and, megathrombocytopenia])]). relacion([sujeto(['The', present, study]), verbo([has]), complemento([used, ultrastructural, 'immunocytochemistry,', 'cytochemistry,', and, tannic, acid, staining, to, answer, questions, raised, in, the, original, investigation])]). relacion([sujeto(['Fully', spread, 'GATA-1', platelets, incubated, with, fibrinogen, coated, gold, '(', 'Fgn/Au)', particles, before, or, after, fixation]), verbo([bound]), complemento([as, many, 'Fgn/Au', particles, as, normal, spread, platelets, and, moved, the, 'Fgn/Au-', 'GPIIb/IIIa', complexes, from, peripheral, margins, to, cell, centers, and, into, channels, of, the, 'OCS', as, efficiently])]). relacion([sujeto(['Spread', 'GATA-1', platelets]), verbo([bound]), complemento([very, few, vWF, 'multimers,', which, were, much, smaller, in, size, than, those, on, normal, spread, 'cells,', but, were, able, to, move, then, to, cell, centers])]). relacion([sujeto(['The', marked]), verbo([decrease]), complemento([in, the, number, and, abnormal, distribution, of, 'GPIb/IX', receptors, may, play, a, role, in, 'GATA-1', megathrombocyte, formation])]). relacion([sujeto(['Genetic', alterations, of, each, are]), verbo([associated]), complemento([with, abnormal, platelet, 'development,', as, well, as, predisposition, to, leukemia])]). relacion([sujeto(['In', 'addition,', in, vitro, and, animal, studies, indicate, that, both, factors, are]), verbo([involved]), complemento([in, megakaryopoiesis])]). relacion([sujeto(['We', and, others]), verbo([have]), complemento([previously, shown, that, 'RUNX1', and, 'GATA-1', physically, interact, and, cooperate, in, the, activation, of, megakaryocytic, promoters, such, as, alpha, 'IIb', integrin, and, glycoprotein, 'Ibalpha'])]). relacion([sujeto(['Moreover,', transcriptional, cooperation, of, 'RUNX1', with, 'GATA-1', is]), verbo([conserved]), complemento([back, to, 'Drosophila', in, which, 'RUNX1', and, 'GATA-1', homologs, cooperate, in, crystal, cell, development])]). relacion([sujeto(['In', 'particular,', we, will, elaborate, on, recent, data, which]), verbo([suggest]), complemento([that, 'GATA-1', targets, 'RUNX1', for, 'modification,', in, particular, phosphorylation, by, 'cyclin-dependent', kinases])]). relacion([sujeto(['Furthermore,']), verbo([targeting]), complemento([of, 'RUNX1', by, 'GATA-1', for, phosphorylation, may, convert, 'RUNX1', from, a, repressor, to, an, activator])]). relacion([sujeto(['HOXA10', is, a, member, of, the, 'HOX', family, of, regulatory, genes, that, are]), verbo([involved]), complemento([in, hematopoiesis])]). relacion([sujeto(['Its', role, in, megakaryopoiesis]), verbo([has]), complemento([been, suggested, by, its, expression, in, immature, megakaryocytes, and, by, the, proliferation, of, 'megakaryocyte-primitive', blast, colonies, upon, 'HOXA10', overexpression])]). relacion([sujeto(['Analysis', of, the, 5, '\'', untranslated, region, and, transfection, of, 'promoter/plasmids', into, human, tissue, culture, cell, lines, identified, transcriptionally, active, sequences, that, contain, 'GATA-1', and, 'Ets-1', sites, and, a, putative]), verbo([binding]), complemento([site, for, its, neighboring, 'gene,', 'HOXA11'])]). relacion([sujeto(['Mutation', of, the, 'GATA-1', and, the, 'Ets-1', motifs, amplified, the, expression, of, 'HOXA10', in, 'HEL', and, 'K562', 'cells,', confirming, the, importance, of, these, 'cis-acting', elements, in]), verbo([regulating]), complemento(['HOXA10', expression, in, megakaryocytic, cells])]). relacion([sujeto(['Chromatin', immunoprecipitation, '(', 'ChIP)', and, chloramphenicol, acetyl, transferase, '(', 'CAT)', assays, confirm, that, 'HOXA11']), verbo([binds]), complemento([to, the, putative, binding, 'site,', resulting, in, repression, of, 'HOXA10', expression])]). relacion([sujeto(['Activated', mast, cells, produce, 'Th2', cytokines, that]), verbo([regulate]), complemento([allergic, inflammation])]). relacion([sujeto(['We']), verbo([have]), complemento([previously, shown, that, thymoquinone, '(', 'TQ)', attenuated, airway, inflammation, in, a, mouse, model, of, allergic, airway, inflammation])]). relacion([sujeto(['RBL-2H3', cells, were]), verbo([stimulated]), complemento([for, 12, h, with, 0.1, 'microg/ml', 'LPS', in, the, presence, or, absence, of, 10, microM, 'TQ'])]). relacion([sujeto(['The', in, vivo]), verbo([binding]), complemento([of, 'GATA,', 'AP-1', and, 'NF-AT', transcription, factors, to, 'IL-5', promoter, was, assessed, by, chromatin, immunoprecipitation, analysis])]). relacion([sujeto([5, ')']), verbo([inhibited]), complemento(['LPS-induced', 'IL-5', and, 'IL-13', mRNA, expression, and, protein, production])]). relacion([sujeto(['GATA', transcription, factors, are]), verbo([involved]), complemento([in, the, transcription, of, 'IL-5', and, 'IL-13'])]). relacion([sujeto(['Chromatin', immunoprecipitation, revealed, that, 'GATA,', 'AP-1', and, 'NF-AT']), verbo([binding]), complemento([to, 'IL-5', promoter, was, induced, by, 'LPS', stimulation, and, that, 'TQ', inhibited, 'GATA', binding, at, the, 'IL-5', promoter, but, did, not, affect, 'AP-1', and, 'NF-AT', binding])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, 'TQ', inhibits, 'LPS-induced', proinflammatory, cytokine, production, in, 'RBL-2H3', cells, by, blocking, 'GATA', transcription, factor, expression, and, promoter, binding, which, demonstrates, the, 'anti-inflammatory', effect, of, 'TQ'])]). relacion([sujeto(['To', investigate, 'this,', we, developed, models, of, arteriogenesis, using, the, zebrafish, 'embryo,', which]), verbo([gains]), complemento([sufficient, oxygenation, via, diffusion, to, prevent, ischemia, in, response, to, arterial, occlusion])]). relacion([sujeto(['In', many, developing, 'tissues,', signaling]), verbo([mediated]), complemento([by, activation, of, the, transmembrane, receptor, 'Notch', influences, 'cell-fate', 'decisions,', 'differentiation,', 'proliferation,', and, cell, survival])]). relacion([sujeto(['Notch', receptors, are]), verbo([expressed]), complemento([on, hematopoietic, cells, and, cognate, ligands, on, bone, marrow, stromal, cells])]). relacion([sujeto(['Multipotent', 'FDCP-mix', cell, lines, engineered, to, permit, the, conditional, induction, of, the, constitutively, active, intracellular, domain, of, mNotch1, '(', 'mN1(IC))', by, the, 4, -, hydroxytamoxifen, '(', 'OHT)-inducible', system, were, used, to, analyze, the, effects, of]), verbo([activated]), complemento([mNotch1, on, erythroid, differentiation, and, on, expression, of, 'Gata1,', 'Fog1,', 'Eklf,', 'NF-E2,', and, 'beta-globin'])]). relacion([sujeto(['Induction', of, 'mN1(IC)', by, 'OHT', resulted, in]), verbo([increased]), complemento([and, accelerated, differentiation, of, 'FDCP-mix', cells, along, the, erythroid, lineage])]). relacion([sujeto(['Erythroid', maturation, was]), verbo([induced]), complemento([by, activated, 'Notch1', also, under, conditions, that, normally, promote, 'self-renewal,', but, required, the, presence, of, erythropoietin, for, differentiation, to, proceed])]). relacion([sujeto(['Concomitantly', with, erythroid, 'differentiation,']), verbo([activated]), complemento([mNotch1, upregulated, 'beta-globin', 'RNA'])]). relacion([sujeto(['Notch', signaling, transactivated, a, reporter, construct, harboring, a]), verbo([conserved]), complemento(['RBP-J', '(', 'CBF1)', binding, site, in, the, hypersensitive, site, 2, '(', 'HS2)', of, human, 'beta-globin'])]). relacion([sujeto(['Transactivation', by]), verbo([activated]), complemento(['Notch', was, completely, abolished, when, this, 'RBP-J', site, was, mutated, to, prevent, 'RBP-J', binding])]). relacion([sujeto(['Our', results, show, that, activation, of, mNotch1]), verbo([induces]), complemento([erythroid, differentiation, in, cooperation, with, erythropoietin, and, upregulates, 'beta-globin', expression])]). relacion([sujeto(['Here,', we]), verbo([report]), complemento([that, 'GATA-1', and, 10, haematopoietic, factors, '(', 'SCL,', 'NF-E2,', 'EKLF,', 'Pleckstrin,', 'Thrombin-R,', 'LMO2,', 'PU'])]). relacion([sujeto([98, ')', ',', and, putative, 'GATA-1-binding', sites, are]), verbo([found]), complemento([in, almost, all, promoters, of, these, genes])]). relacion([sujeto(['In', 'addition,', luciferase, reporter, assays]), verbo([reveal]), complemento([that, mutations, of, 'GATA-1-binding', sites, in, the, 'GATA-1', promoter, abolish, its, sensitivity, to, 'HDAC', 'inhibitor-mediated', 'down-regulation', in, 'HEL', cells])]). relacion([sujeto(['Further,', this]), verbo([report]), complemento([also, asserts, that, 'HDAC', inhibitor, increases, megakaryocyte, counts, and, inhibits, 'GATA-1', gene, expression, in, rat, spleen])]). relacion([sujeto(['Together,', these, results]), verbo([suggest]), complemento([that, 'HDAC', inhibitors, inhibit, 'GATA-1', gene, expression, by, decreasing, the, transactivation, function, of, 'GATA-1', 'itself,', and, that, this, may, in, turn, lead, to, a, delay, in, megakaryocyte, maturation, and, finally, cause, thrombocytopenia])]). relacion([sujeto(['SET-CAN']), verbo([associated]), complemento([with, the, 't(9;9)', in, acute, undifferentiated, leukemia, encodes, almost, the, entire, sequence, of, 'SET', and, the, 'C-terminal', 'two-third', portion, of, 'CAN,', including, the, 'FG', repeat, region])]). relacion([sujeto(['To', clarify, a, 'role(s)', of, 'SET-CAN', in, 'leukemogenesis,', we, developed, transgenic, mice]), verbo([expressing]), complemento(['SET-CAN', under, the, control, of, the, 'Gata1', gene, hematopoietic, regulatory, domain, that, is, active, in, distinct, sets, of, hematopoietic, cells])]). relacion([sujeto(['We']), verbo([found]), complemento([that, a, significant, number, of, 'c-kit+', myeloid, cells, appeared, in, peripheral, blood, in, transgenic, mice])]). relacion([sujeto(['Molecules']), verbo([involved]), complemento([in, this, process, are, members, of, highly, conserved, families, of, proteins, that, exert, conserved, functions, across, species])]). relacion([sujeto(['Bone', morphogenetic, proteins, '(', 'BMP)', are, extracellular, factors, that, are]), verbo([regulated]), complemento([by, extracellular, modulators, and, bind, to, 'BMP', 'receptors,', which, in, turn, activate, intracellular, signaling, cascades])]). relacion([sujeto(['It', is]), verbo([expressed]), complemento([at, sites, of, high, 'BMP', 'activity,', including, vascular, precursor, cells, located, in, the, aortic, arches, and, the, intermediate, cell, mass, during, zebrafish, embryonic, development])]). relacion([sujeto(['Knockdown', of, zbmper, results, in, a, dorsalized, 'phenotype,', a, reduced, number, of, gata1]), verbo([expressing]), complemento([hematopoietic, precursor, cells, and, of, circulating, blood, cells, as, well, as, in, a, vascular, phenotype])]). relacion([sujeto(['The', generation, of, the, caudal, vein, is, compromised, and, the, pattern, guiding, of, the, intersomitic, vessels, is, 'disturbed,', indicating, that, zbmper, is]), verbo([required]), complemento([for, early, steps, in, vascular, pattern, formation, and, hematopoiesis, in, zebrafish])]). relacion([sujeto(['To']), verbo([gain]), complemento([insight, into, 'host-microbe', interactions, in, a, piglet, 'model,', a, functional, genomics, approach, was, used, to, address, the, working, hypothesis, that, transcriptionally, regulated, genes, associated, with, promoting, epithelial, barrier, function, are, activated, as, a, defensive, response, to, the, intestinal, microbiota])]). relacion([sujeto(['Consistent', with, our, 'hypothesis,', resident, microbiota]), verbo([induced]), complemento([the, expression, of, genes, contributing, to, intestinal, epithelial, cell, 'turnover,', mucus, 'biosynthesis,', and, priming, of, the, immune, system])]). relacion([sujeto(['Furthermore,', differential, expression, of, genes]), verbo([associated]), complemento([with, antigen, presentation, '(', pan, 'SLA', class, 'I,', 'B2M,', 'TAP1', and, 'TAPBP)', demonstrated, that, microbiota, induced, immune, responses, using, a, distinct, regulatory, mechanism, common, for, these, genes])]). relacion([sujeto(['Specifically,', gene, network, analysis, revealed, that, microbial, colonization]), verbo([activated]), complemento([both, type, 'I', '(', 'IFNAR)', and, type, 'II', '(', 'IFNGR)', interferon, receptor, mediated, signaling, cascades, leading, to, enhanced, expression, of, signal, transducer, and, activator, of, transcription, 1, '(', 'STAT1),', 'STAT2', and, 'IFN', regulatory, factor, 7, '(', 'IRF7)', transcription, factors, and, the, induction, of, 'IFN-inducible', genes, as, a, reflection, of, intestinal, epithelial, inflammation])]). relacion([sujeto(['In', 'addition,']), verbo([activated]), complemento(['RNA', expression, of, 'NF-kappa-B', inhibitor, alpha, '(', 'NFkappaBIA;', a])]). relacion([sujeto([a, 'I-kappa-B-alpha,', 'IKBalpha)', and, toll]), verbo([interacting]), complemento([protein, '(', 'TOLLIP),', both, inhibitors, of, 'inflammation,', along, with, downregulated, expression, of, the, immunoregulatory, transcription, factor, 'GATA', binding, 'protein-1', '(', 'GATA1)', is, consistent, with, the, maintenance, of, intestinal, homeostasis])]). relacion([sujeto(['This', study, supports, the, concept, that, the, intestinal, epithelium]), verbo([has]), complemento([evolved, to, maintain, a, physiological, state, of, inflammation, with, respect, to, continuous, microbial, 'exposure,', which, serves, to, sustain, a, tight, intestinal, barrier, while, preventing, overt, inflammatory, responses, that, would, compromise, barrier, function])]). relacion([sujeto(['Capsaicin,', the, pungent, component, of, chilli, 'peppers,', is, known, to]), verbo([induce]), complemento([mediators, of, hematopoiesis])]). relacion([sujeto(['Treatment', of, mouse, bone, marrow, cells, with, capsaicin]), verbo([induced]), complemento([the, formation, of, colony, of, 'burst-forming', 'units-erythroid', '(', 'BFU-E)'])]). relacion([sujeto(['We', also]), verbo([found]), complemento([that, the, number, of, erythropoietin, receptor, '(', 'EpoR)-positive', cells, was, increased, by, capsaicin])]). relacion([sujeto(['Quantitative', 'RT-PCR', analysis, revealed, that, capsaicin]), verbo([stimulated]), complemento([the, expression, of, the, 'erythroid-specific', genes, encoding, 'EpoR,', glycophorin, 'A', '(', 'GPA),', 'beta-globin', '(', 'Hbb-b1),', 'GATA-1,', 'PU'])]). relacion([sujeto([1, ',']), verbo([nuclear]), complemento([factor, 'erythroid-derived', 2, '(', 'NF-E2),', and, 'Krüppel-like', factor, 1, '(', 'KLF1)', in, the, 'BFU-E', colonies])]). relacion([sujeto(['Furthermore,', capsaicin, could, effectively]), verbo([stimulate]), complemento([the, transfected, 'GATA-1', promoter, in, 'K562', cells])]). relacion([sujeto(['Our', results, show, that, development, of, the, erythroid, lineage, from, bone, marrow, cells, can, be]), verbo([induced]), complemento([by, treatment, with, 'capsaicin,', and, that, 'GATA-1', seems, to, play, a, role, in, this, induced, erythroid, maturation])]). relacion([sujeto(['A', 34, -, 'year-old', woman, was, referred, for, evaluation, of, a, recent, stillborn, male, 'fetus,', gestational, age, 27, 6, /, 7, 'weeks,']), verbo([found]), complemento([to, have, congenital, myeloid, leukemia, at, autopsy])]). relacion([sujeto([1, was]), verbo([suppressed]), complemento([in, the, resistant, clones, albeit, the, 'spleen-focus', forming, virus, was, still, integrated, in, the, proximity, of, the, 'Sfpi-1', locus])]). relacion([sujeto(['Exposure', to, 5, -, 'Aza-2\'-deoxycytidine']), verbo([activates]), complemento(['PU'])]). relacion([sujeto([1, expression]), verbo([suggesting]), complemento([that, the, 'PU'])]). relacion([sujeto(['Altogether', these, results]), verbo([suggest]), complemento([that, 'PU'])]). relacion([sujeto(['Erythropoietin', '(', 'Epo)', and, its, cognate, receptor, '(', 'EpoR)', are]), verbo([required]), complemento([for, maintaining, adequate, levels, of, circulating, erythrocytes, during, embryogenesis, and, adulthood])]). relacion([sujeto(['Here,', we]), verbo([report]), complemento([the, functional, characterization, of, the, zebrafish, epo, and, epor, genes])]). relacion([sujeto(['The', expression, of, epo, and, epor, was, evaluated, by, quantitative, reverse, 'transcriptase-polymerase', chain, reaction, '(', 'RT-PCR)', and, 'whole-mount', in, situ, 'hybridization,']), verbo([revealed]), complemento([marked, parallels, between, zebrafish, and, mammalian, gene, expression, patterns])]). relacion([sujeto(['Examination', of, the, hypochromic, 'mutant,', 'weissherbst,', and, adult, 'hypoxia-treated', hearts, indicate, that, zebrafish, epo, expression, is]), verbo([induced]), complemento([by, anemia, and, hypoxia])]). relacion([sujeto(['Overexpression', of, epo, mRNA, resulted, in, severe, 'polycythemia,', characterized, by, a, striking]), verbo([increase]), complemento([in, the, number, of, cells, expressing, 'scl,', 'c-myb,', 'gata1,', 'ikaros,', 'epor,', and, 'betae1-globin,', suggesting, that, both, the, erythroid, progenitor, and, mature, erythrocyte, compartments, respond, to, epo])]). relacion([sujeto(['Morpholino-mediated', knockdown, of, the, epor]), verbo([caused]), complemento([a, slight, decrease, in, primitive, and, complete, block, of, definitive, erythropoiesis])]). relacion([sujeto(['Together,', the, characterization, of, zebrafish, epo, and, epor, demonstrates, the, conservation, of, an, ancient, program, that]), verbo([ensures]), complemento([proper, red, blood, cell, numbers, during, normal, homeostasis, and, under, hypoxic, conditions])]). relacion([sujeto(['PGE(2)', is]), verbo([involved]), complemento([in, a, wide, variety, of, physiological, and, pathological, 'processes;', 'however,', deciphering, its, role, in, early, mammalian, development, has, been, difficult, due, to, the, maternal, contribution, of, 'PGE(2)'])]). relacion([sujeto(['To', overcome, this, limitation, we]), verbo([have]), complemento([investigated, the, role, of, 'PGE(2)', during, 'T', cell, development, in, zebrafish])]). relacion([sujeto(['In', this, 'study,', we, show, that, zebrafish, 'ep4a,', a, 'PGE(2)', receptor, isoform, of, 'EP4,', is]), verbo([expressed]), complemento([at, 26, h, postfertilization, in, the, dorsal, 'aorta-posterior', cardinal, vein, joint, 'region,', which, has, a, high, homology, with, the, mammal, 'aorta-gonad-mesonephros', area, and, where, definitive, hemopoiesis, arises])]). relacion([sujeto(['Furthermore,', it, is]), verbo([expressed]), complemento([in, the, presumptive, thymus, rudiment, by, 48, h, postfertilization])]). relacion([sujeto(['Supplementation', of, 'PGE(2)', results, in, a, strong]), verbo([increase]), complemento([in, rag1, levels, and, cell, proliferation, in, the, thymus])]). relacion([sujeto(['An', in, utero, origin, of, the, 'GATA1', mutation]), verbo([suggests]), complemento([it, is, an, early, leukemogenic, event])]). relacion([sujeto(['Hispanic', newborns, were, 2.6, times, more, likely, to]), verbo([have]), complemento([a, mutated, 'GATA1', gene, than, 'non-Hispanics', '(', 'P', =])]). relacion([sujeto(['Two', newborns, with, a, 'GATA1', mutation, subsequently, developed, 'AMKL,', and, none, of, the, infants, without, a, functional, 'GATA1', mutation, were]), verbo([reported]), complemento([to, have, developed, leukemia])]). relacion([sujeto(['In', addition, to, screening, for, 'TL,', a, 'GATA1', mutation, at, birth, might, serve, as, a, biomarker, for, an]), verbo([increased]), complemento([risk, of, 'DS-related', 'AMKL'])]). relacion([sujeto(['Furthermore,', 'GATA-1', expression, levels, were]), verbo([found]), complemento([to, correlate, with, the, disease, progression])]). relacion([sujeto(['MDS', patients, in, 'high/INT-2', 'IPSS', risk, group]), verbo([expressed]), complemento([significantly, higher, 'GATA-1', mRNA, 'levels,', in, both, 'CD34(+)', and, 'CD71(+)', 'cells,', as, opposed, to, 'low/INT-1', patients, '(', 'P', &, 'lt;', 0.001, ')'])]). relacion([sujeto(['Moreover,', the, former, displayed]), verbo([increased]), complemento([apoptosis, in, the, 'CD71(+)', cells, and, significantly, reduced, neutrophil, and, platelet, numbers, and, hemoglobin, levels, compared, with, the, latter])]). relacion([sujeto(['We', conclude, that, 'MDS', patients, display, an]), verbo([increase]), complemento([of, 'GATA-1', mRNA, expression, in, 'BM', 'cells,', with, 'high/INT-2', patients, showing, significantly, higher, levels])]). relacion([sujeto(['These', findings]), verbo([suggest]), complemento([that, the, 'up-regulation', of, 'GATA-1', may, be, responsible, for, the, peripheral, cytopenias, in, 'MDS'])]). relacion([sujeto(['It']), verbo([regulates]), complemento([many, haematopoietic, genes, and, interacts, with, a, number, of, other, transcription, factors])]). relacion([sujeto(['Its', functions, are, mostly]), verbo([conserved]), complemento([among, vertebrates])]). relacion([sujeto(['These', observations]), verbo([suggest]), complemento([the, importance, of, regulation, on, the, expression, level, and, timing, of, 'GATA1'])]). relacion([sujeto(['Janus', kinase, 2, '(', 'Jak2)', transduces, signals, from, hematopoietic, 'cytokines,', and, a, 'gain-of-function', mutation, '(', 'Jak2(617V>F))', is]), verbo([associated]), complemento([with, myeloproliferative, 'diseases,', particularly, polycythemia, vera])]). relacion([sujeto(['In', this, 'study,', we, examined, the, role, of, jak2a, in, zebrafish, embryos, in, 'knock-down', and, overexpression, studies, using, morpholinos, '(', 'MOs)']), verbo([targeting]), complemento([the, 5, '\'', untranslated, region, '(', 'UTR)', '(', 'jak2a(UTR)-MO)', and, 'splice-site', junction, '(', 'jak2a(SS)-MO)', of, 'jak2a,', a, 'Jak', inhibitor, 'AG490', and, a, 'constitutive-active', form, of, jak2a, '(', 'jak2a(ca))'])]). relacion([sujeto(['At', 18, and, 24, hours, after, fertilization, '(', 'hpf),', jak2a, is]), verbo([expressed]), complemento([predominantly, in, the, intermediate, cell, mass, '(', 'ICM;', site, of, primitive, 'hematopoiesis)', of, 'wild-type', and, chordin, morphant, embryos, '(', characterized, by, expansion, of, 'ICM)'])]). relacion([sujeto(['Both', jak2a, 'MOs', and, 'AG490', reduced, 'gata1(+)', '(', 'erythroid)', cells, in, 'Tg(gata1:GFP)', 'embryos,', signal, transducer, and, activation, of, transcription, 5, '(', 'stat5)', 'phosphorylation,', and, gene, expression]), verbo([associated]), complemento([with, early, progenitors, '(', scl, and, 'lmo2)', and, erythroid, '(', 'gata1,', alphahe1, and, 'betahe1)', and, myeloid, '(', spi1, '[', 'early]', and, mpo, '[', 'late])', lineages])]). relacion([sujeto(['The', chordin, morphant, is]), verbo([associated]), complemento([with, increased, stat5, 'phosphorylation,', and, both, jak2a, 'MOs', and, treatment, with, 'AG490', significantly, ameliorated, 'ICM', expansion, and, hematopoietic, gene, 'up-regulation', in, these, embryos])]). relacion([sujeto(['Injection', of, plasmid, encoding, 'jak2a(ca)', significantly]), verbo([increased]), complemento([erythropoiesis, and, expression, of, 'gata1,', alphahe1, and, 'betahe1,', 'spi1,', 'mpo,', and, 'l-plastin'])]). relacion([sujeto(['In', 'conclusion,', zebrafish, jak2a, is]), verbo([involved]), complemento([in, primitive, hematopoiesis, under, normal, and, deregulated, conditions])]). relacion([sujeto(['The', present, study]), verbo([has]), complemento([carried, out, detailed, ultrastructural, studies, of, abnormal, platelet, morphology, in, 'one,', previously, described, family, with, a, 'GATA-1', 'G208S', mutation])]). relacion([sujeto(['The', unique, pathology, of, the, 'GATA-1', family, platelets]), verbo([found]), complemento([in, this, study, involved, features, never, observed, previously, in, normal, or, abnormal, platelets])]). relacion([sujeto(['GATA-1', platelets, within, platelets, and, attached, to, 'platelets,', as, well, as, giant, 'platelets,']), verbo([suggest]), complemento([that, proplatelet, formation, may, be, 'abnormal,', or, that, 'GATA-1', platelets, are, unable, to, pinch, off, from, megakaryocyte, proplatelets, in, a, normal, manner])]). relacion([sujeto(['Extra', copies, of, chromosome, 21, are, often]), verbo([found]), complemento([in, sporadic, leukemias])]). relacion([sujeto(['Constitutional', trisomy, 21, of, 'Down', syndrome, '(', 'DS)', is]), verbo([associated]), complemento([with, markedly, increased, risk, for, childhood, leukemia])]). relacion([sujeto(['Recent', studies, of, the, megakaryoblastic, leukemias, of, 'Down', syndrome]), verbo([have]), complemento([uncovered, a, developmental, leukemogenic, mechanism, characterized, by, a, unique, 'pre-natal', collaboration, between, overexpressed, genes, from, chromosome, 21, and, an, acquired, mutation, in, the, transcription, factor, 'GATA1'])]). relacion([sujeto(['The', base, of, the, markedly]), verbo([enhanced]), complemento([risk, for, acute, lymphoblastic, leukemia, conferred, by, trisomy, 21, is, still, unclear])]). relacion([sujeto(['Dendritic', cell, commitment, and, function]), verbo([require]), complemento([orchestrated, regulation, of, transcription])]). relacion([sujeto(['Gata1', is, a, transcription, factor]), verbo([expressed]), complemento([in, several, hematopoietic, lineages])]). relacion([sujeto(['However,', 'Gata1', function]), verbo([has]), complemento([not, been, explored, in, the, monocytic, or, dendritic, cell, compartment])]). relacion([sujeto(['Here,', we, show, that, 'Gata1', is]), verbo([expressed]), complemento([in, myeloid, and, plasmacytoid, dendritic, cells, and, that, 'Gata1', ablation, affects, the, survival, of, dendritic, cells])]). relacion([sujeto(['Furthermore,', lipopolysaccharide, '(', 'LPS)', stimulation, of, dendritic, cells, prompts, 'Gata1', 'up-regulation,', which, is, accompanied, by]), verbo([increased]), complemento([levels, of, 'BclX', and, 'Ifng'])]). relacion([sujeto(['Our', findings, show, that, 'Gata1', is, a, transcriptional, regulator, of, dendritic, cell, differentiation, and]), verbo([suggest]), complemento([that, 'Gata1', is, involved, in, the, dendritic, cell, and, macrophage, lineage, separation])]). relacion([sujeto(['In', the, two, mouse, models, of, myelofibrosis]), verbo([caused]), complemento([by, targeting, 'megakaryocytopoesis,', 'wide,', 'pericyte-coated', and, morphologically, aberrant, vessels, were, detected])]). relacion([sujeto(['Mast', cell, differentiation, in, the, marrow, is]), verbo([activated]), complemento([as, part, of, the, body, response, to, parasites])]). relacion([sujeto(['The', rapidly]), verbo([increasing]), complemento([availability, of, 'microarray-derived', global, gene, expression, data, 'sets,', coupled, with, genome, sequence, information, from, multiple, 'species,', has, driven, the, development, of, computational, methods, to, reverse, engineer, and, dynamically, model, genetic, regulatory, networks])]). relacion([sujeto(['Using', complementation, analysis, with, 'GATA-1-null', cells, and, mice, containing, a, hypomorphic, allele, of, the, chromatin, remodeler, 'BRG1,', we, dissected, the, pathway, from, 'GATA-1']), verbo([binding]), complemento([to, cofactor, 'recruitment,', chromatin, loop, 'formation,', and, transcriptional, activation])]). relacion([sujeto(['Analysis', of, 'GATA-1-mediated', activation, of, the, 'beta-globin', 'locus,', in, which, 'GATA-1', assembles, dispersed, complexes, at, the, promoters, and, the, distal, locus, control, region, '(', 'LCR),', revealed, molecular, 'intermediates,', including, 'GATA-1-independent', and, 'GATA-1-containing', 'LCR', 'subcomplexes,', both, defective, in]), verbo([promoting]), complemento([loop, formation])]). relacion([sujeto(['An', additional, intermediate, consisted, of, an, apparently, normal, 'LCR', complex, and, a, promoter, complex, with, reduced, levels, of, total, 'RNA', polymerase, 'II', '(', 'Pol', 'II)', and, 'Pol', 'II']), verbo([phosphorylated]), complemento([at, serine, 5, of, the, 'carboxy-terminal', domain])]). relacion([sujeto(['Reduced', 'BRG1', activity, solely, compromised, 'Pol', 'II', and, serine, 5, -]), verbo([phosphorylated]), complemento(['Pol', 'II', occupancy, at, the, 'promoter,', phenocopying, the, 'LCR-deleted', mouse])]). relacion([sujeto(['Single-stranded', 'DNA-binding', proteins, '(', 'SSBPs)', were, recently, shown, to]), verbo([interact]), complemento([with, 'Ldb1', and, are, also, important, in, developmental, programs])]). relacion([sujeto(['We', establish, here, that, two, mammalian, 'SSBPs,', 'SSBP2', and, 'SSBP3,', contribute, to, an, erythroid, 'DNA-binding', complex, that, contains, the, transcription, factors, 'Tal1', and, 'GATA-1,', the, 'LIM', domain, protein, 'Lmo2,', and, 'Ldb1', and]), verbo([binds]), complemento([a, bipartite, 'E-box-GATA', 'DNA', sequence, motif])]). relacion([sujeto(['In', 'addition,', 'SSBP2', was]), verbo([found]), complemento([to, augment, transcription, of, the, 'Protein', 4.2, '(', 'P4'])]). relacion([sujeto([2, ')', 'gene,', a, direct]), verbo([target]), complemento([of, the, 'E-box-GATA-binding', 'complex,', in, an, 'Ldb1-dependent', manner, and, to, increase, endogenous, 'Ldb1', and, 'Lmo2', protein, 'levels,', 'E-box-GATA', 'DNA-binding', 'activity,', and, 'P4'])]). relacion([sujeto(['Finally,', 'SSBP2', was, demonstrated, to]), verbo([inhibit]), complemento(['Ldb1', and, 'Lmo2', interaction, with, the, 'E3', ubiquitin, ligase, 'RLIM,', prevent, 'RLIM-mediated', 'Ldb1', 'ubiquitination,', and, protect, 'Ldb1', and, 'Lmo2', from, proteasomal, degradation])]). relacion([sujeto(['These', results, define, a, novel, biochemical, function, for, 'SSBPs', in]), verbo([regulating]), complemento([the, abundance, of, 'LIM', domain, and, 'LIM', 'domain-binding', proteins])]). relacion([sujeto(['Upon', 'I/11', cell, 'induction,', histone, modifications, 'changed,', the, 'ACH', was, 'formed,', and, the, 'beta-globin-like', genes, were]), verbo([transcribed]), complemento([at, rates, similar, to, those, observed, in, vivo])]). relacion([sujeto(['Moreover,', we, used, 'knock-out', mice, to, show, that, the, erythroid, transcription, factor, p45, 'NF-E2,', which]), verbo([has]), complemento([been, implicated, in, 'beta-globin', gene, 'regulation,', is, dispensable, for, 'beta-globin', 'ACH', formation])]). relacion([sujeto(['The', 'erythroid-specific', transcriptional, network, that]), verbo([regulates]), complemento(['Bcl-x(L)', expression, in, erythropoiesis, remains, unclear])]). relacion([sujeto(['The', activation, of, the, central, erythropoietic, transcriptional, 'factor,', 'GATA-1,']), verbo([leads]), complemento([to, the, 'early,', transient, induction, of, a, transcription, 'repressor,', 'Gfi-1B,', followed, by, the, late, induction, of, 'Bcl-x(L)', during, erythroid, maturation, in, 'G1ER', cells])]). relacion([sujeto(['Chromatin', immunoprecipitation, assays, demonstrated, that, a, constant, level, of, 'GATA-1']), verbo([binds]), complemento([to, the, 'Bcl-x', promoter, throughout, the, entire, induction, 'period,', while, 'Gfi-1B', is, transiently, associated, with, the, promoter, in, the, early, phase])]). relacion([sujeto(['Here,', we, present, evidence, that, 'GATA-1']), verbo([binds]), complemento([to, the, noncanonical, 'GATT', motif, of, the, 'Bcl-x', promoter, for, 'trans-activation'])]). relacion([sujeto(['Gfi-1B']), verbo([expressed]), complemento([at, increased, levels, is, recruited, to, the, 'Bcl-x', promoter, through, its, association, with, 'GATA-1,', suppressing, 'Bcl-x(L)', transcription])]). relacion([sujeto(['Furthermore,', we, show, that, the, inhibition, of, 'Bcr-Abl', kinase, by, treatment, with, imatinib]), verbo([caused]), complemento([the, 'up-regulation', of, 'Gfi-1B', in, 'K562', 'cells,', where, 'Gfi-1B', also, cooperated, with, 'GATA-1', to, repress, 'Bcl-x(L)', transcription])]). relacion([sujeto([1, ',', which]), verbo([regulate]), complemento([the, choice, between, erythroid, and, myelomonocytic, fates])]). relacion([sujeto([1, mRNA, and, transcriptome, dynamics, of, differentiating, progenitor, cells, confirm, that, commitment, occurs, in, two, 'stages,', as]), verbo([suggested]), complemento([by, the, 'model:', 'first,', the, progenitor, state, is, destabilized, in, an, almost, symmetrical, bifurcation, 'event,', resulting, in, a, poised, state, at, the, boundary, between, the, two, 'lineage-specific', 'attractors;', 'second,', the, cell, is, driven, to, the, 'respective,', now, accessible, attractors])]). relacion([sujeto(['We', previously]), verbo([reported]), complemento([a, new, 'megakaryocytic-erythroid', cell, 'line,', 'JAS-R'])]). relacion([sujeto(['Adhesion', of, 'JAS-RAD', was]), verbo([inhibited]), complemento([by, treatment, with, 'RGDS', oligopeptide])]). relacion([sujeto(['Microarray', analysis, and, 'RT-PCR', revealed, that, 'JAS-RAD', cells]), verbo([expressed]), complemento([four, major, 'alpha-granule', genes, and, 'JAS-REN', cells, expressed, 'beta-globin'])]). relacion([sujeto(['With', regard, to, transcription, 'factors,', it, was, shown, that, 'GFI1,', 'FLI1', and, 'RUNX1', were, strongly]), verbo([expressed]), complemento([in, 'JAS-RAD', cells, while, 'GATA1,', 'FOG1', and, 'NFE2', were, equally, expressed, by, both, types])]). relacion([sujeto(['GATA-1', possesses, the, ability, to, 'self-associate,', and, this, characteristic]), verbo([has]), complemento([been, suggested, to, be, important, for, 'GATA-1', function])]). relacion([sujeto(['We', generated, transgenic, mouse, lines, that]), verbo([express]), complemento([these, 'GATA-1', mutants, utilizing, the, 'Gata1', hematopoietic, regulatory, 'domain,', and, crossed, the, mice, to, 'Gata1', knockdown, '(', 'GATA-1'])]). relacion([sujeto(['These', results]), verbo([provide]), complemento([the, first, convincing, line, of, evidence, that, the, 'self-association', of, 'GATA-1', is, important, for, proper, mammalian, erythroid, development, in, vivo])]). relacion([sujeto(['The', mechanism, of, osteosclerosis]), verbo([associated]), complemento([with, myelofibrosis, in, megakaryocyte, '(', 'MK)-related', myeloproliferative, disorders, is, largely, unknown])]). relacion([sujeto(['However,', growth, factors]), verbo([released]), complemento([from, the, bone, marrow, 'cells,', including, from, 'MKs,', have, been, implicated, in, 'myelofibrosis,', 'osteosclerosis,', and, angiogenesis])]). relacion([sujeto(['GATA-1', is, a, transcription, factor]), verbo([required]), complemento([for, normal, 'MK', development])]). relacion([sujeto(['GATA-1', deficiency, in, mice, '(', 'GATA-1(low))']), verbo([leads]), complemento([to, increased, megakaryocytic, 'proliferation,', followed, by, osteosclerosis, and, myelofibrosis])]). relacion([sujeto(['Presence', of, 'BMP', protein, in, the, bone, marrow, of, 'GATA-1(low)', mice, was, more, than, that, seen, in, 'controls,', owing, to, an]), verbo([increased]), complemento([number, of, 'MKs', and, osteoblasts])]). relacion([sujeto(['The']), verbo([increased]), complemento([levels, of, 'BMPs', appear, to, be, a, result, of, increased, numbers, of, 'MKs', in, 'GATA-1(low)', mice, and, 'may,', in, 'part,', account, for, the, stimulation, of, osteoblastic, activity, and, resulting, osteosclerosis])]). relacion([sujeto(['Two', transcripts, of, 'LMO2', gene, '(', 'LMO2-a', and, 'LMO2-b)']), verbo([have]), complemento([been, reported, to, encode, a, same, 158, -, 'amino-acid', protein])]). relacion([sujeto(['We']), verbo([have]), complemento([previously, reported, a, novel, transcript, of, human, 'LMO2', gene, '(', 'LMO2-c)', encoding, a, 151, -, 'amino-acid', 'protein,', and, defined, its, promoter, region])]). relacion([sujeto(['We']), verbo([found]), complemento([that, 'LMO2-c', expression, is, regulated, by, the, cooperation, of, two, essential, hematopoietic, transcription, factors, 'GATA-1', and, 'PU'])]). relacion([sujeto([1, in, various, hematopoietic, cell, 'lines,']), verbo([suggesting]), complemento([an, important, functional, role, for, 'LMO2-c', in, the, hematopoietic, system])]). relacion([sujeto(['More', 'importantly,', we, demonstrated, that, 'LMO2-c']), verbo([acts]), complemento([as, an, antagonist, of, 'LMO2-a/b', binding, to, its, 'partners,', therefore, blocking, the, transactivation, of, 'LMO2-a/b', on, its, target, genes])]). relacion([sujeto(['These', findings]), verbo([provide]), complemento([novel, evidence, to, the, functions, of, 'LMO2', gene, in, the, hematopoietic, system, and, leukemia])]). relacion([sujeto(['For', 'example,', 'GATA-1', and, 'GATA-2', occupy, five]), verbo([conserved]), complemento([regions, over, approximately, 100, kb, of, the, 'Gata2', locus, in, the, transcriptionally, repressed, and, active, 'states,', 'respectively,', in, erythroid, cells])]). relacion([sujeto(['Since', it, is, unknown, whether, the, individual, complexes, exert, qualitatively, distinct, or, identical, functions, to]), verbo([regulate]), complemento(['Gata2', transcription, in, 'vivo,', we, compared, the, activity, of, the, -, 3.9, and, +, 9.5, kb, sites, of, the, 'Gata2', locus, in, transgenic, mice])]). relacion([sujeto(['Surprisingly,', whereas, this, 'GATA-E-box', composite, motif, was, sufficient, for, enhancer, activity, in, an, erythroid, precursor, cell, 'line,', its, enhancer, function, in, primary, human, endothelial, cells]), verbo([required]), complemento([additional, regulatory, modules])]). relacion([sujeto(['These', results, identify, the, first, molecular, determinant, of, 'Gata2', transcription, in, vascular, 'endothelium,', composed, of, a, core, enhancer, module, active, in, both, endothelial, and, hematopoietic, cells, and, regulatory, modules, preferentially]), verbo([required]), complemento([in, endothelial, cells])]). relacion([sujeto(['The', 'GATA-1-interacting', protein, 'Friend', 'Of', 'GATA-1', '(', 'FOG-1)', is, essential, for, the, proper, transcriptional, activation, and, repression, of, numerous, 'GATA-1']), verbo([target]), complemento([genes])]). relacion([sujeto(['Although', 'FOG-1-independent', activation, by, 'GATA-1']), verbo([has]), complemento([been, 'described,', all, known, examples, of, 'GATA-1-mediated', repression, are, 'FOG-1', dependent])]). relacion([sujeto(['In', the, 'GATA-1-null', 'G1E', cell, 'line,', estrogen, receptor, ligand]), verbo([binding]), complemento([domain, '(', 'ER)', chimeras, of, either, 'wild-type', 'GATA-1', or, a, 'FOG-1-binding', defective, mutant, of, 'GATA-1', repressed, several, genes, similarly, upon, activation, with, 'beta-estradiol'])]). relacion([sujeto(['Repression', also, occurred, in, a, 'FOG-1-null', cell, line]), verbo([expressing]), complemento(['ER-GATA-1', and, during, ex, vivo, erythropoiesis])]). relacion([sujeto(['At', the, 'Lyl1', and, 'Rgs18', 'loci,', we]), verbo([found]), complemento([highly, restricted, occupancy, by, 'GATA-1', and, 'GATA-2,', indicating, that, these, genes, are, direct, targets, of, 'GATA', factor, regulation])]). relacion([sujeto(['The', nucleotide, excision, repair, '(', 'NER)', pathway, and, its]), verbo([leading]), complemento([gene, 'excision-repair', 'cross-complementary', 1, '(', 'ERCC1)', have, been, shown, to, be, 'up-regulated', in, hepatocellular, carcinomas, even, in, the, absence, of, treatment, with, chemotherapeutics])]). relacion([sujeto(['The', aim, of, this, study, was, to, determine, the, mechanism]), verbo([involved]), complemento([in, 'NER', regulation, during, the, liver, cell, growth, observed, in, hepatocellular, carcinoma])]). relacion([sujeto(['Both', 'NER', activity, and, 'ERCC1', expression, were]), verbo([increased]), complemento([after, exposure, to, the, epidermal, growth, factor, '(', 'EGF)', in, cultured, normal, and, tumoral, human, hepatocytes])]). relacion([sujeto(['These']), verbo([increases]), complemento([correlated, with, the, activation, of, the, kinase, signaling, pathway, 'mitogen-activated', 'protein/extracellular', 'signal-regulated', kinase, '(', 'ERK)', kinase, '(', 'MEK)/ERK', that, is, known, to, be, a, key, regulator, in, the, 'G(1)', phase, of, the, hepatocyte, cell, cycle])]). relacion([sujeto(['Moreover,', 'EGF-mediated', activation, of, 'ERCC1', was, specifically]), verbo([inhibited]), complemento([by, either, the, addition, of, 'U0126,', a, 'MEK/ERK', inhibitor, or, small, interfering, 'RNA-mediated', knockdown, of, 'ERK2'])]). relacion([sujeto(['Basal', expression, of, 'ERCC1', was]), verbo([decreased]), complemento([in, the, presence, of, the, 'phosphoinositide-3-kinase', '(', 'PI3K)', inhibitor, and, small, hairpin, 'RNA', '(', 'shRNA)', against, the, 'PI3K', pathway, kinase, 'FKBP12-rapamycin-associated', protein, or, mammalian, target, of, rapamycin])]). relacion([sujeto(['Transient', transfection, of, human, hepatocytes, with, constructs, containing, different, sizes, of, the, 5, '\'', -, flanking, region, of, the, 'ERCC1', gene, upstream, of, the, luciferase, reporter, gene, showed, an]), verbo([increase]), complemento([in, luciferase, activity, in, 'EGF-treated', 'cells,', which, correlated, with, the, presence, of, the, nuclear, transcription, factor, 'GATA-1', recognition, sequence])]). relacion([sujeto(['Endomitosis', is, a, unique, form, of, cell, cycle, used, by, 'megakaryocytes,', in, which, the, latter, stages, of, mitosis, are, bypassed, so, that, the, cell, can]), verbo([increase]), complemento([its, 'DNA', content, and, size])]). relacion([sujeto(['Although', several, transcription, 'factors,', including, 'GATA-1', and, 'RUNX-1,']), verbo([have]), complemento([been, implicated, in, this, 'process,', the, link, between, transcription, factors, and, polyploidization, remains, undefined])]). relacion([sujeto(['Here', we, show, that, 'GATA-1-deficient', 'megakaryocytes,', which, display, reduced, size, and, 'polyploidization,']), verbo([express]), complemento([nearly, 10, -, fold, less, cyclin, 'D1', and, 10, -, fold, increased, levels, of, p16, compared, with, their, 'wild-type', counterparts])]). relacion([sujeto(['We', further, demonstrate, that, cyclin, 'D1', is, a, direct, 'GATA-1']), verbo([target]), complemento([in, 'megakaryocytes,', but, not, erythroid, cells])]). relacion([sujeto(['Restoration', of, cyclin, 'D1', 'expression,', when, accompanied, by, ectopic, overexpression, of, its, partner, 'Cdk4,', resulted, in, a, dramatic]), verbo([increase]), complemento([in, megakaryocyte, size, and, 'DNA', content])]). relacion([sujeto(['Finally,', consistent, with, an, additional, defect]), verbo([conferred]), complemento([by, increased, levels, of, 'p16,', inhibition, of, cyclin, 'D-Cdk4', complexes, with, a, 'TAT-p16', fusion, peptide, significantly, blocked, polyploidization, of, 'wild-type', megakaryocytes])]). relacion([sujeto(['Together,', these, data, show, that, 'GATA-1', controls, growth, and, polyploidization, by]), verbo([regulating]), complemento([cyclin, 'D-Cdk4', kinase, activity])]). relacion([sujeto(['Phospholipase', 'C', '(', 'PLC)', gamma, 1]), verbo([has]), complemento([been, shown, to, mediate, signal, transduction, of, tyrosine, kinases, and, affect, function, of, hematopoietic, cells])]). relacion([sujeto(['In', this, 'study,', we, examined, this, issue, using, morpholino, '(', 'MO)', gene, knockdown, in, zebrafish, embryos, 'MO']), verbo([targeting]), complemento([at, the, 'exon-1-intron-1', junction, of, zebrafish, 'PLC-gamma1', was, injected, into, embryos, at, the, 'one-', to, 'four-cell', stage, '(', referred, herein, 'zPLC-gamma1(MO)', 'embryos)'])]). relacion([sujeto(['PLC-gamma1', is]), verbo([involved]), complemento([in, the, regulation, of, primitive, hematopoiesis, in, zebrafish, 'embryos,', which, is, distinct, from, its, later, effect, on, vascular, formation])]). relacion([sujeto(['In', the, stabilized, 'samples,', we]), verbo([found]), complemento([very, high, pairwise, correlation, in, gene, expression, '(', 'DeltaDeltaC(T)', 0.16, -, 0.53, ')', for, the, analyzed, genes, '(', 'GATA1,', 'RUNX1,', 'NCAM1,', and, 'SPI1)', after, 48, -, h, storage, compared, with, immediate, preparation, of, 'RNA', '(', 2, h, after, 'BM', 'collection)'])]). relacion([sujeto(['However,', we]), verbo([found]), complemento([major, differences, in, half, of, the, analyzed, genes, using, the, reference, 'RNA', isolation, procedure, '(', 'DeltaDeltaC(T)', 1.07, and, 1.32, ')'])]). relacion([sujeto(['Zebrafish', cebpa, is]), verbo([expressed]), complemento([in, the, anterior, and, posterior, lateral, plate, mesoderm, at, 12, hours, 'postfertilization,', along, with, 'scl,', pu])]). relacion([sujeto(['In', 'vitro,', the, deletion, mutation, of, cebpa, '(', 'zD420)']), verbo([prevents]), complemento([expression, of, the, 'full-length', 'protein,', allowing, the, expression, of, truncated, isoforms, from, internal, translational, initiation, sites])]). relacion([sujeto(['As', in, the, 'human,', the, truncated, zebrafish, 'C/EBPalpha', proteins, did, not]), verbo([activate]), complemento([the, expression, of, known, target, granulocytic, 'genes,', and, in, fact, suppressed, transactivation, that, was, induced, in, vitro, by, the, 'full-length', protein])]). relacion([sujeto(['Forced', expression, of, the, zD420, mRNA, in, zebrafish, embryos]), verbo([led]), complemento([to, an, expansion, of, primitive, 'erythropoiesis,', without, a, discernible, effect, on, granulopoiesis])]). relacion([sujeto(['The', 'GATA', family, of, transcription, factors, appears, to]), verbo([retain]), complemento([conserved, roles, in, early, germ, layer, patterning, in, 'most,', if, not, 'all,', 'animals;', 'however,', the, number, and, structure, of, 'GATA', factor, genes, varies, substantially, when, different, animal, genomes, are, compared])]). relacion([sujeto(['We', identified, two, highly]), verbo([conserved]), complemento(['GATA', factor, genes, in, a, marine, 'annelid,', the, polychaete, 'Platynereis', dumerilii])]). relacion([sujeto(['We', also, identified]), verbo([conserved]), complemento([motifs, within, each, 'GATA', 'class,', and, assigned, the, divergent, 'Caenorhabditiselegans', and, 'Drosophila', melanogaster, 'GATA', factor, genes, to, the, vertebrate, classes])]). relacion([sujeto(['Our', results, show, that, distinct, orthologs, of, the, two, vertebrate, 'GATA', factor, classes, exist, in, a, protostome, 'invertebrate,']), verbo([suggesting]), complemento([that, bilaterian, 'GATA', factors, originated, from, 'GATA1/2/3', and, 4, /, 5, /, 6, ancestral, orthologs])]). relacion([sujeto(['Moreover,', our, results, indicate, that, the, 'GATA', gene, duplication, and, the, functional, divergence, that]), verbo([led]), complemento([to, these, two, ancestral, 'GATA', factor, genes, occurred, after, the, split, of, the, bilaterian, stem, group, from, the, cnidarians])]). relacion([sujeto(['Studies', within, the, past, 'year,', described, within, this, 'review,']), verbo([have]), complemento([provided, tremendous, insights, into, the, role, of, 'GATA1', mutations, in, these, malignancies])]). relacion([sujeto(['In', the, past, 'year,', our, understanding, of, the, molecular, and, cellular, consequences, of, 'GATA1', mutations]), verbo([has]), complemento([been, greatly, enhanced])]). relacion([sujeto(['Most', 'importantly,', we]), verbo([have]), complemento([learned, that, these, 'mutations,', which, result, in, the, exclusive, production, of, the, short, 'GATA1', isoform, named, 'GATA1s,', have, a, distinct, effect, on, fetal, liver, progenitors])]). relacion([sujeto(['In', 'addition,', multiple, studies]), verbo([have]), complemento([shown, that, 'GATA1s', can, substitute, for, 'GATA1', in, many, aspects, of, megakaryocytic, maturation])]). relacion([sujeto(['Finally,', an, important, clinical, study]), verbo([has]), complemento([revealed, that, 'GATA1', mutations, alone, are, insufficient, for, leukemia])]). relacion([sujeto(['Leukemia', in, children, with, 'Down', syndrome]), verbo([requires]), complemento([at, least, three, cooperating, 'events--trisomy', 21, ',', a, 'GATA1', 'mutation,', and, a, 'third,', as, yet, 'undefined,', genetic, alteration])]). relacion([sujeto(['Recent', studies]), verbo([have]), complemento([provided, tremendous, insights, into, the, 'GATA1', side, of, the, story])]). relacion([sujeto(['Future', experiments, with, human, patient, samples, and, mouse, models, will, likely]), verbo([increase]), complemento([our, awareness, of, the, role, of, trisomy, 21, in, transient, myeloproliferative, disorder, and, acute, megakaryocytic, leukemia])]). relacion([sujeto(['Hematopoiesis', in, vertebrate, development]), verbo([involves]), complemento([an, 'embryonic,', primitive, wave, and, a, 'later,', definitive, wave, in, which, embryonic, blood, cells, are, replaced, with, adult, blood, cells])]). relacion([sujeto(['We', here, show, that, zebrafish, fgf1, is]), verbo([involved]), complemento([in, vivo, in, primitive, hematopoiesis])]). relacion([sujeto(['Fibroblast', growth, 'factor-1', '(', 'FGF1)', morpholino, knockdown]), verbo([leads]), complemento([to, abnormal, accumulation, of, blood, cells, in, the, posterior, intermediate, cell, mass, at, 32, hr, postfertilization])]). relacion([sujeto(['Expression', of, the, erythroid, markers, gata1, and, 'ika,', normally, diminishing, in, differentiating, erythrocytes, at, this, 'stage,', is]), verbo([maintained]), complemento([at, abnormally, high, levels, in, primitive, blood, cells])]). relacion([sujeto(['Zebrafish', fgf1, is, syntenic, to, human, 'FGF1,', which, maps, to, a, critically, deleted, region, in, human, 'del(5q)', syndrome, posing, an]), verbo([increased]), complemento([risk, of, leukemia, to, patients])]). relacion([sujeto(['As', its, knockdown, in, zebrafish, changes, expression, of, 'gata1,', a, gene]), verbo([involved]), complemento([in, hematopoietic, stem, cell, 'decisions,', 'FGF1', should, be, considered, to, play, a, role, in, the, pathogenesis, of, 'del(5q)', syndrome])]). relacion([sujeto(['This', mutation, was, previously, described, as, a]), verbo([cause]), complemento([of, 'X-linked', thrombocytopenia, with, thalassemia, '(', 'XLTT)', but, not, of, gray, platelet, syndrome])]). relacion([sujeto(['Our', findings]), verbo([suggest]), complemento([that, 'XLTT', is, within, a, spectrum, of, disorders, constituting, the, gray, platelet, 'syndrome,', and, we, propose, that, 'GATA1', is, an, upstream, regulator, of, the, genes, required, for, platelet, 'alpha-granule', biogenesis])]). relacion([sujeto(['This', early, death]), verbo([prevents]), complemento([the, analysis, of, the, role, of, 'Runx1', in, the, development, of, sensory, ganglia])]). relacion([sujeto(['In', 'Runx1-deficient', 'mice,', the, total, number, of, dorsal, root, ganglion, '(', 'DRG)', neurons, was, 'increased,', probably, because, of, an]), verbo([increased]), complemento([proliferative, activity, of, 'DRG', progenitor, cells, and, decreased, apoptosis])]). relacion([sujeto(['Our', results]), verbo([suggest]), complemento([that, 'Runx1', is, involved, in, the, cell, fate, specification, of, cutaneous, 'neurons,', as, well, as, their, projections, to, central, and, peripheral, targets])]). relacion([sujeto(['The', function, of, several, transcription, factors]), verbo([has]), complemento([been, reported, in, hematopoietic, stem, cell, differentiation])]). relacion([sujeto(['The', 'Zfpm-1', siRNA, transfected, 'HSCs', contained, 20, '%', more, 'GPA+', cells, than, the, mock, transfected, 'cells,', and, showed, repressed, expression, of, the, hematopoietic, transcription, 'factors,', 'c-myc', and, 'c-myb,', but]), verbo([increased]), complemento([expression, of, 'GATA-1'])]). relacion([sujeto(['GATA-1', is, a, hematopoietic, transcription, factor]), verbo([expressed]), complemento([in, 'erythroid,', 'megakaryocytic,', mast, cell, and, eosinophil, lineages])]). relacion([sujeto(['It', is]), verbo([required]), complemento([for, normal, erythroid, 'differentiation,', the, expression, of, 'erythroid-specific', genes, and, for, the, establishment, of, an, active, chromatin, structure, throughout, the, 'beta-globin', gene, locus])]). relacion([sujeto(['To', determine, whether, 'GATA-1', was, sufficient, to, direct, formation, of, the, locus, control, region, '(', 'LCR)', and, an, erythroid, pattern, of, gene, 'expression,', we]), verbo([expressed]), complemento(['GATA-1', in, the, 'non-hematopoietic', 'HeLa', cell, line, that, does, not, express, other, hematopoietic, transcription, factors, but, does, express, 'GATA-2,', 'GATA-3,', and, 'GATA-6'])]). relacion([sujeto(['We']), verbo([found]), complemento([that, production, of, the, 'GATA-1', protein, resulted, in, the, formation, of, 'LCR', 'DNase', 'I', 'HSs', 1, -, 4, in, their, normal, 'locations,', and, that, histones, became, hyperacetylated, within, these, regulatory, elements])]). relacion([sujeto(['Transcription', of, several, 'erythroid-specific', genes, was]), verbo([activated]), complemento([in, 'HeLa', cells, expressing, 'GATA-1,', including, those, coding, for, 'alpha-globin,', 'beta-globin,', the, erythropoietin, 'receptor,', the, erythroid, 'krüpple-like', factor, and, p45, 'NF-E2'])]). relacion([sujeto(['Despite']), verbo([increased]), complemento([expression, of, these, genes, at, the, mRNA, 'level,', their, protein, products, were, not, detected])]). relacion([sujeto(['GATA', transcriptional, factors, such, as, 'GATA-1', and, 'GATA-2', are]), verbo([expressed]), complemento([in, mast, 'cells,', and, recent, studies, have, revealed, that, both, 'GATA-1', and, 'GATA-2', are, required, for, mast, cell, development])]). relacion([sujeto(['However,', the, role, of, 'GATA', transcriptional, factors, in, differentiated, mast, cells]), verbo([has]), complemento([remained, largely, unknown])]). relacion([sujeto(['Surprisingly,', the, repression, of, 'GATA', activity, in, differentiated, mast, cells]), verbo([led]), complemento([to, the, impairment, of, cell, 'survival,', 'IgE-induced', 'degranulation,', and, cytokine, production])]). relacion([sujeto(['These', results, identify, that, 'GATA']), verbo([has]), complemento([a, critical, role, in, the, activation, of, mast, cell])]). relacion([sujeto(['In', response, to, erythropoietin, '(', 'Epo),', erythroid, progenitors, undergo, differentiation, in, vitro, and]), verbo([express]), complemento(['erythroid-specific', genes, such, as, 'betamajor-globin,', 'Alas2,', 'MafK,', 'p45,', 'Eklf,', and, 'Gata1'])]). relacion([sujeto(['Expression', of, these, genes, was]), verbo([decreased]), complemento([in, the, presence, of, 'NAC,', whereas, the, expression, of, 'c-myb,', which, is, downregulated, during, erythroid, 'differentiation,', remained, constant])]). relacion([sujeto(['Moreover,', 'NAC', treatment]), verbo([inhibited]), complemento([an, increase, in, the, number, of, cells, expressing, high, levels, of, 'erythroid-specific', antigen, 'TER119'])]). relacion([sujeto(['Treatment', with, another, 'antioxidant,', pyrrolidine, 'dithiocarbamate,', also]), verbo([caused]), complemento([the, attenuation, of, 'TER119', expression])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, reactive, oxygen, species, are, involved, in, 'Epo-mediated', erythroid, differentiation])]). relacion([sujeto(['Caspase-3', is]), verbo([activated]), complemento([during, both, terminal, differentiation, and, 'erythropoietin-starvation-induced', apoptosis, of, human, erythroid, precursors])]). relacion([sujeto(['The', transcription, factor, 'GATA-1,', which, performs, an, essential, function, in, erythroid, differentiation, by, positively]), verbo([regulating]), complemento([promoters, of, erythroid, and, 'anti-apoptotic', 'genes,', is, cleaved, by, caspases, in, erythroid, precursors, undergoing, cell, death, upon, erythropoietin, starvation, or, engagement, of, the, death, receptor, 'Fas'])]). relacion([sujeto(['At', the, onset, of, caspase, 'activation,', 'Hsp70', 'co-localizes', and]), verbo([interacts]), complemento([with, 'GATA-1', in, the, nucleus, of, erythroid, precursors, undergoing, terminal, differentiation])]). relacion([sujeto(['In', 'contrast,', erythropoietin, starvation]), verbo([induces]), complemento([the, nuclear, export, of, 'Hsp70', and, the, cleavage, of, 'GATA-1'])]). relacion([sujeto(['The', use, of, 'RNA-mediated', interference, to]), verbo([decrease]), complemento([the, 'Hsp70', content, of, erythroid, precursors, cultured, in, the, presence, of, erythropoietin, leads, to, 'GATA-1', 'cleavage,', a, decrease, in, haemoglobin, 'content,', downregulation, of, the, expression, of, the, 'anti-apoptotic', protein, 'Bcl-X(L),', and, cell, death, by, apoptosis])]). relacion([sujeto(['Thus,', in, erythroid, precursors, undergoing, terminal, 'differentiation,', 'Hsp70']), verbo([prevents]), complemento([active, 'caspase-3', from, cleaving, 'GATA-1', and, inducing, apoptosis])]). relacion([sujeto(['These', results]), verbo([provide]), complemento([evidence, of, the, presence, of, 'GATA-1(+)', hemangioblastic, cells, in, the, 'extra-embryonic', region, and, also, their, functional, contribution, to, hematopoiesis, in, the, embryo])]). relacion([sujeto(['There', is, an]), verbo([increased]), complemento([risk, of, myeloid, malignancy, in, individuals, with, 'Down\'s', syndrome, '(', 'DS),', which, is, associated, with, a, mutation, in, exon, 2, of, the, transcription, factor, 'GATA-1'])]). relacion([sujeto(['It', is]), verbo([recognized]), complemento([that, there, is, accelerated, telomere, shortening, in, blood, cells, of, children, with, 'DS', similar, to, that, in, conditions, such, as, 'Fanconi', anemia, and, dyskeratosis, congenita])]). relacion([sujeto(['The', latter, conditions, are]), verbo([associated]), complemento([with, stem, cell, deficiency, and, clonal, 'change,', including, acute, myeloid, leukemia])]). relacion([sujeto(['In', this, study, we, address, the, questions, 1, ')', whether, the, accelerated, telomere, shortening, is]), verbo([associated]), complemento([with, 'progenitor/stem', cell, deficiency, in, individuals, with, 'DS,', predisposing, to, clonal, change, and, 2, ')', whether, the, occurrence, of, reduced, numbers, of, 'stem/progenitor', cells, precede, the, incidence, of, mutations, in, exon, 2, of, 'GATA-1'])]). relacion([sujeto(['We']), verbo([found]), complemento([that, hematopoietic, 'stem/progenitor', cell, deficiency, and, telomere, shortening, occurs, in, individuals, with, 'DS', in, fetal, life])]). relacion([sujeto(['Moreover,', the, presence, of, a, low, number, of, progenitor, cells, was, not]), verbo([associated]), complemento([with, mutations, in, exon, 2, of, 'GATA-1'])]). relacion([sujeto(['Deficiency', of, 'UROS', results, in, excess, uroporphyrin, 'I,', which]), verbo([causes]), complemento([photosensitization])]). relacion([sujeto(['No', 'UROS', or, 'alpha-', and, 'beta-globin', mutations, were]), verbo([found]), complemento([in, the, child, or, the, parents])]). relacion([sujeto(['This', is, the, first]), verbo([report]), complemento([of, a, human, porphyria, due, to, a, mutation, in, a, 'trans-acting', factor, and, the, first, association, of, 'CEP', with, thalassemia, and, thrombocytopenia])]). relacion([sujeto(['The', 'Hb', 'F', level, of, 59.5, '%']), verbo([suggests]), complemento([a, role, for, 'GATA-1', in, globin, switching])]). relacion([sujeto(['Mediator', subunit, 'Med1/TRAP220', is, a, key, component, of, 'Mediator', originally]), verbo([found]), complemento([to, associate, with, nuclear, hormone, receptors])]). relacion([sujeto(['Med1', deficiency]), verbo([causes]), complemento([lethality, at, embryonic, day, 11.5, because, of, defects, in, heart, and, placenta, development])]). relacion([sujeto(['Here', we, show, that, 'Med1-deficient', 10.5, days, postcoitum, embryos, are, anemic, but]), verbo([have]), complemento([normal, numbers, of, hematopoietic, progenitor, cells])]). relacion([sujeto(['Med1-deficient', progenitor, cells]), verbo([have]), complemento([a, defect, in, forming, erythroid, 'burst-forming', units, '(', 'BFU-E)', and, 'colony-forming', units, '(', 'CFU-E),', but, not, in, forming, myeloid, colonies])]). relacion([sujeto(['At', the, molecular, 'level,', we, demonstrate, that, 'Med1']), verbo([interacts]), complemento([physically, with, the, erythroid, master, regulator, 'GATA-1'])]). relacion([sujeto(['In', transcription, 'assays,', 'Med1', deficiency]), verbo([leads]), complemento([to, a, defect, in, 'GATA-1-mediated', transactivation])]). relacion([sujeto(['In', chromatin, immunoprecipitation, 'experiments,', we]), verbo([find]), complemento(['Mediator', components, at, 'GATA-1-occupied', enhancer, sites])]). relacion([sujeto(['Thus,', we, conclude, that, 'Mediator', subunit, 'Med1']), verbo([acts]), complemento([as, a, pivotal, coactivator, for, 'GATA-1', in, erythroid, development])]). relacion([sujeto(['Platelets', are, produced, by, megakaryocytes, in, a, process, that]), verbo([involves]), complemento([the, formation, of, platelet, precursors, called, proplatelets, and, subsequent, release, of, these, proplatelets, into, the, circulation])]). relacion([sujeto(['However,', several, groups]), verbo([have]), complemento([contributed, evidence, to, unveil, the, role, of, thrombopoietin, '(', 'TPO),', the, principal, regulator, of, megakaryopoiesis, in, vivo])]). relacion([sujeto(['Several', transcription, factors]), verbo([have]), complemento([also, been, implicated, in, megakaryopoiesis, 'including,', 'GATA-1,', friend, of, 'GATA-1', '(', 'FOG-1),', nuclear, 'factor-erythroid', 2, '(', 'NF-E2),', and, 'Fli-1'])]). relacion([sujeto(['In', 'fact,', interactions, among, some, of, the, transcription, factors]), verbo([have]), complemento([been, reported, to, produce, synergistic, effects])]). relacion([sujeto(['Mutations', in, the, vWF, complex, and, alphaIIb, beta3]), verbo([have]), complemento([been, linked, to, disorders, such, as, 'Bernard-Soulier', syndrome, and, 'Glazmann', thrombasthenia, respectively])]). relacion([sujeto(['Therefore,', a, more, comprehensive, understanding, of, the, transcriptional, control, of, megakaryopoiesis, may]), verbo([lead]), complemento([to, more, effective, treatments, of, 'platelet-related', disorders])]). relacion([sujeto(['EF-2']), verbo([regulates]), complemento([the, outcome, of, protein, synthesis, in, mammalian, cells])]). relacion([sujeto(['This']), verbo([report]), complemento([demonstrates, that, chicken, 'EF-2', protein, levels, are, dependent, on, transcription, in, 8, -, 'bromo-cAMP,', insulin, and, phorbol, 'ester-treated', cells])]). relacion([sujeto(['The', region, between, -, 700, and, -, 550]), verbo([has]), complemento([a, negative, regulatory, region, and, two, regulatory, proteins, '(', 'I,', 'II)'])]). relacion([sujeto([8, -, 'bromo-cAMP']), verbo([increased]), complemento([chicken, 'EF-2', promoter, activity, '(', -, 700, /, +, 102, ')', in, 'Rat', 1, 'HIR', fibroblast, cells, more, than, insulin, and, phorbol, ester, treatment])]). relacion([sujeto(['Binding', of, protein, 'I', and, 'II', were]), verbo([decreased]), complemento([by, 8, -, 'bromo-cAMP', but, restored, by, a, protein, kinase, 'A', inhibitor, '(', 'KT5720)'])]). relacion([sujeto(['GATA', consensus, sequence, oligonucleotide, and, fragment, -, 86, /, -, 50]), verbo([prevented]), complemento([protein, 'II', binding, of, fragment, -, 700, /, -, 550])]). relacion([sujeto(['This', result]), verbo([suggested]), complemento([that, protein, 'II', is, a, 'GATA-like', protein])]). relacion([sujeto(['These', observations]), verbo([provide]), complemento([a, novel, regulatory, mechanism, for, the, 'EF-2', promoter])]). relacion([sujeto(['The', 'Duffy', blood, group, 'Ag', '(', 'dfy)']), verbo([binds]), complemento([selective, 'CXC', and, 'CC', chemokines, at, high, affinity, and, is, expressed, on, erythrocytes, and, endothelial, cells])]). relacion([sujeto(['We', hypothesized, that, dfy, functions, as, a, chemokine, reservoir, and]), verbo([regulates]), complemento([inflammation, by, altering, soluble, chemokine, concentrations, in, the, blood, and, tissue, compartments])]). relacion([sujeto(['We', determined, whether, 'Duffy', 'Ag', &, 'quot;loss-of-function"', phenotypes, '(', human, and, 'murine)', are]), verbo([associated]), complemento([with, alterations, in, plasma, chemokine, concentrations, during, the, innate, inflammatory, response, to, 'LPS'])]). relacion([sujeto(['Mice', lacking, erythrocyte, dfy, had, higher, 'MIP-2', and, keratinocyte, chemoattractant, concentrations, in, the, lung, tissue, vascular, 'space,', but, lower, plasma, chemokine, concentrations]), verbo([associated]), complemento([with, attenuated, neutrophil, recruitment, into, the, airspaces])]). relacion([sujeto(['These', data, indicate, that, dfy, alters, soluble, chemokine, concentrations, in, blood, and, local, tissue, compartments, and]), verbo([enhances]), complemento([systemic, bioavailability, of, chemokines, produced, during, local, tissue, inflammation])]). relacion([sujeto(['Ldb1,', a, ubiquitously]), verbo([expressed]), complemento(['LIM', domain, binding, 'protein,', is, essential, in, a, number, of, tissues, during, development])]). relacion([sujeto(['It']), verbo([interacts]), complemento([with, 'Gata1,', 'Tal1,', 'E2A', and, 'Lmo2', to, form, a, transcription, factor, complex, regulating, late, erythroid, genes])]). relacion([sujeto(['We', identify, a, number, of, novel, 'Ldb1']), verbo([interacting]), complemento([proteins, in, erythroleukaemic, 'cells,', in, particular, the, repressor, protein, 'Eto-2', '(', and, its, family, member, 'Mtgr1),', the, 'cyclin-dependent', kinase, 'Cdk9,', and, the, bridging, factor, 'Lmo4'])]). relacion([sujeto(['Human', chronic, myelogenous, leukemia, '(', 'CML)', cell, line, 'K562', can, be, chemically]), verbo([induced]), complemento([to, differentiate, and, express, embryonic, and, fetal, globin, genes])]). relacion([sujeto(['Our', results, revealed, that, 'DOX,', 'EDOX', and, their, derivatives]), verbo([caused]), complemento([irreversible, differentiation, of, 'K562', cells, into, more, mature, 'hemoglobin-containing', cells])]). relacion([sujeto(['An']), verbo([increase]), complemento([of, 'gamma-globin', mRNA, level, caused, both, by, high, transcription, rate, and, by, mRNA, 'stabilization,', as, well, as, an, enhancement, of, expression, but, not, activity, of, erythroid, transcription, factor, 'GATA-1', were, observed])]). relacion([sujeto(['Over', the, last, four, years, there]), verbo([has]), complemento([been, considerable, progress, in, our, understanding, of, 'DS', 'AMKL'])]). relacion([sujeto(['These', are, the, minimum]), verbo([required]), complemento([events, for, 'TMD', to, develop])]). relacion([sujeto(['In', approximately, 30, '%', of, 'TMD', 'patients,', additional, as, yet, unidentified, '(', 'epi)genetic', mutations, are]), verbo([required]), complemento([for, progression, to, 'AMKL'])]). relacion([sujeto(['Thus,', 'DS', 'TMD', and, 'AMKL']), verbo([provide]), complemento([a, unique, model, of, childhood, leukaemia, where, the, preleukaemic, and, leukaemic, phases, are, ascertainable, and, separable, allowing, distinct, steps, in, leukaemogenesis, to, be, studied, individually])]). relacion([sujeto(['These', findings, also]), verbo([have]), complemento([implications, for, the, clinical, management, of, 'DS', 'TMD', and, 'AMKL', specifically, and, also, of, childhood, leukaemia, more, generally])]). relacion([sujeto(['Increased', erythrocyte, mean, corpuscular, volume, '(', 'MCV)', is, frequently]), verbo([found]), complemento([among, 'DS', infants, and, remains, elevated, throughout, life, in, 'two-thirds', of, 'patients,', making, interpretation, of, red, cell, indices, for, diagnosis, of, nutritional, anemias, or, bone, marrow, failure, disorders, more, challenging])]). relacion([sujeto(['Transient', myeloproliferative, disorder, '(', 'TMD)']), verbo([associated]), complemento([with, 'pancytopenia,', 'hepatosplenomegaly,', and, circulating, immature, 'WBCs,', is, found, almost, exclusively, in, 'DS', infants, with, an, incidence, of, approximately, 10, '%'])]). relacion([sujeto(['There', is, an]), verbo([increased]), complemento([risk, of, leukemia, with, an, equal, incidence, of, lymphoid, and, myeloid, leukemia])]). relacion([sujeto(['Somatic', mutations, of, the, gene, encoding, the, hematopoetic, growth, factor, 'GATA1']), verbo([have]), complemento([been, shown, to, be, specific, for, 'TMD', and, 'AMKL', in, children, with, 'DS'])]). relacion([sujeto(['Children', with, 'DS', and, leukemia, are, more, sensitive, to, some, chemotherapeutic, agents, such, as, methotrexate, than, other, children, which]), verbo([requires]), complemento([careful, monitoring, for, toxicity])]). relacion([sujeto(['Although', the, risk, for, leukemia, is, higher, in, individuals, with, 'DS,', these, patients]), verbo([have]), complemento([a, lower, risk, of, developing, solid, 'tumors,', with, the, exception, of, germ, cell, 'tumors,', and, perhaps, retinoblastoma, and, lymphoma])]). relacion([sujeto(['Megakaryocyte', '(', 'MK)', differentiation, is, well, described, in, morphologic, terms, but, its, molecular, counterparts, and, the, basis, for, platelet]), verbo([release]), complemento([are, incompletely, understood])]). relacion([sujeto(['Genes']), verbo([associated]), complemento([with, 'DNA', replication, are, highly, expressed, in, young, 'MKs,', in, parallel, with, endomitosis])]). relacion([sujeto(['Intermediate', stages, are, characterized, by, disproportionate, expression, of, genes]), verbo([associated]), complemento([with, the, 'cytoskeleton,', cell, 'migration,', and, 'G-protein', 'signaling,', whereas, terminally, mature, 'MKs', accumulate, hemostatic, 'factors,', including, many, membrane, proteins])]). relacion([sujeto(['Computational', analysis, of, the, promoters, of, 'late-expressed', 'MK', genes, identified, new, candidate]), verbo([targets]), complemento([for, 'NF-E2,', a, critical, transcriptional, regulator, of, platelet, release])]). relacion([sujeto(['One', such, gene, encodes, the, kinase, adaptor, protein, 'LIMS1/PINCH1,', which, is, highly]), verbo([expressed]), complemento([in, 'MKs', and, platelets, and, significantly, reduced, in, 'NF-E2-deficient', cells])]). relacion([sujeto(['Transactivation', studies, and, chromatin, immunoprecipitation, implicate, 'Lims1', as, a, direct]), verbo([target]), complemento([of, 'NF-E2', regulation])]). relacion([sujeto(['Such', a, change, might, affect, the, full, ensemble, of]), verbo([target]), complemento([genes, for, a, factor, or, only, uniquely, sensitive, targets])]). relacion([sujeto(['We', investigated, the, relationship, among, activity, of, the, hematopoietic, transcription, factor, 'GATA-1,', chromatin, 'occupancy,', and]), verbo([target]), complemento([gene, sensitivity])]). relacion([sujeto(['Thus,', cells]), verbo([expressing]), complemento([different, levels, of, a, cell, 'type-specific', activator, can, have, qualitatively, distinct, target, gene, expression, 'patterns,', and, factor, mutations, preferentially, deregulate, 'low-sensitivity', genes])]). relacion([sujeto(['Unlike', other]), verbo([target]), complemento(['genes,', 'GATA-1-mediated', 'Tac-2', regulation, was, 'bimodal,', with, activation, followed, by, 'repression,', and, the, coregulator, 'Friend', of, 'GATA-1', '(', 'FOG-1)', selectively, mediated, repression])]). relacion([sujeto(['A', 'GATA-1', mutant, defective, in, 'FOG-1']), verbo([binding]), complemento([occupied, a, 'Tac-2', regulatory, region, at, levels, higher, than, 'wild-type', 'GATA-1,', whereas, 'FOG-1', facilitated, chromatin, occupancy, at, a, distinct, target, site])]). relacion([sujeto(['These', results, indicate, that, 'FOG-1', is, a, determinant, of, 'GATA', factor]), verbo([target]), complemento([gene, sensitivity, by, either, facilitating, or, opposing, chromatin, occupancy])]). relacion([sujeto(['Myeloid', leukemia, of, 'Down\'s', syndrome, '(', 'ML-DS)']), verbo([has]), complemento([characteristic, biological, features, '(', e])]). relacion([sujeto(['We', analyzed, 134, bone, marrow, specimens, from, 64, children, with, 'ML-DS', and, 'non-DS', 'AML', during, chemotherapy, and, 7, specimens, from, 'DS', children, 'with-', out, 'leukemia,who', did, not, receive, any, 'chemotherapy,The', specimens, were, analyzed, by, multiparameter, flow, cytometry, and, quantitative, reverse, transcriptase, polymerase, chain, reaction, for, transcription, factors]), verbo([involved]), complemento([in, hematopoiesis])]). relacion([sujeto(['Samples', taken, from, children, with, 'ML-DS', in, complete, remission, during, chemotherapy, aberrantly]), verbo([expressed]), complemento(['CD56', '(', 'NCAM)', at, the, surface, of, monocytic, and, granulocytic, cells])]). relacion([sujeto(['A', significant]), verbo([decrease]), complemento([of, the, amount, of, 'CD33+/CD56+', cells, was, observed, during, and, after, maintenance, therapy])]). relacion([sujeto(['An']), verbo([increased]), complemento([number, of, 'CD33+/CD56+', cells, was, also, present, '(', &, 'gt;85%)', in, children, with, 'DS', who, did, not, receive, 'chemotherapy,', but, showed, a, 'left-shift', '(', due, to, 'infection),', compared, with, 'DS', children, without, 'left-shift', '(', &, 'lt;10%', 'CD33+/CD56+', 'cells)'])]). relacion([sujeto(['We', predict, 'CRMs', for, mammalian, genes]), verbo([expressed]), complemento([in, red, blood, cells, by, combining, two, properties, gleaned, from, 'aligned,', noncoding, genome, 'sequences:', a, positive, regulatory, potential, '(', 'RP)', 'score,', which, detects, similarity, to, patterns, in, alignments, distinctive, for, regulatory, 'regions,', and, conservation, of, a, binding, site, motif, for, the, essential, erythroid, transcription, factor, 'GATA-1'])]). relacion([sujeto(['Within', eight]), verbo([target]), complemento(['loci,', we, tested, 75, noncoding, segments, by, reporter, gene, assays, in, transiently, transfected, human, 'K562', cells, 'and/or', after, 'site-directed', integration, into, murine, erythroleukemia, cells])]). relacion([sujeto(['Segments', with, a, high, 'RP', score, and, a]), verbo([conserved]), complemento([exact, match, to, the, binding, site, consensus, are, validated, at, a, good, rate, '(', 50, '%', -, 100, '%', ',', with, rates, increasing, at, higher, 'RP),', whereas, segments, with, lower, 'RP', scores, or, nonconsensus, binding, motifs, tend, to, be, inactive])]). relacion([sujeto(['Thus,', high, 'RP', in, combination, with, another, feature, of, a, 'CRM,', such, as, a]), verbo([conserved]), complemento([transcription, factor, binding, 'site,', is, a, good, predictor, of, functional, 'CRMs'])]). relacion([sujeto(['Genome-wide', predictions, based, on, 'RP', and, a, large, set, of, 'well-defined', transcription, factor]), verbo([binding]), complemento([sites, are, available, through, servers, at, 'http://www'])]). relacion([sujeto(['Recent', evidence]), verbo([suggests]), complemento([that, mutations, in, the, 'Gata1', gene, may, alter, the, 'proliferation/differentiation', potential, of, hemopoietic, progenitors])]). relacion([sujeto(['By', 'single-cell', cloning, and, sequential, replating, experiments, of, prospectively, isolated, progenitor, 'cells,', we, demonstrate, here, that, the, hypomorphic, 'Gata1low', mutation]), verbo([increases]), complemento([the, proliferation, potential, of, a, unique, class, of, progenitor, 'cells,', similar, in, phenotype, to, adult, common, 'erythroid/megakaryocytic', progenitors, '(', 'MEPs),', but, with, the, &, 'quot;unique"', capacity, to, generate, 'erythroblasts,', 'megakaryocytes,', and, mast, cells, in, vitro])]). relacion([sujeto(['These', results, confirm, the, crucial, role, played, by, 'Gata1', in, hematopoietic, commitment, and, 'identify,', as, a, new]), verbo([target]), complemento([for, the, 'Gata1', 'action,', the, restriction, point, at, which, common, myeloid, progenitors, become, either, 'MEPs', or, 'MCPs'])]). relacion([sujeto(['These', observations]), verbo([suggest]), complemento([that, a, minor, clone, rather, than, the, predominant, clone, at, the, time, of, 'TMD', may, give, rise, to, 'AMKL', later, on])]). relacion([sujeto(['We']), verbo([have]), complemento([previously, reported, that, human, chronic, myeloid, leukemia, '(', 'CML)', 'KU812', and, 'K562', cells, show, inhibited, cellular, proliferation, in, response, to, treatment, with, activin, 'A,', a, member, of, 'TGF-beta', superfamily])]). relacion([sujeto(['Apoptosis', and, erythroid, differentiation, can, be]), verbo([induced]), complemento([in, 'KU812', and, 'K562', 'cells,', respectively])]). relacion([sujeto(['We']), verbo([report]), complemento([herein, that, activin, 'A', induced, the, expression, of, p27KIP1, in, 'CML', cells, along, with, the, induction, of, cellular, differentiation, and, apoptosis])]). relacion([sujeto(['There', are, putative]), verbo([binding]), complemento([sequences, of, 'erythroid-related', transcription, factor, 'GATA-1', in, the, promoter, region, of, the, human, p27KIP1, gene])]). relacion([sujeto(['In', 'addition,', 'ERK', protein, was, rapidly, and, transiently]), verbo([activated]), complemento([with, activin, 'A', in, both, types, of, 'CML', 'cells,', suggesting, that, phosphorylation, of, 'ERK', is, required, for, activin, 'A', signaling, in, 'CML', cells])]). relacion([sujeto(['DS-TL', neonates]), verbo([have]), complemento([a, approximately, 15, '%', risk, of, developing, potentially, fatal, liver, disease, and, show, &, 'lt;10%', incidence, of, hydrops, fetalis])]). relacion([sujeto(['The', pathogenesis, of, 'DS-TL', '(', and, of, subsequent, acute, 'leukemia)']), verbo([involves]), complemento([mutation, of, 'GATA1', '(', on, chromosome, 'X),', which, normally, encodes, a, transcription, factor, integral, to, normal, development, of, 'erythroid,', 'megakaryocytic,', and, 'basophilic/mast', cell, lines])]). relacion([sujeto(['Though', indications, for, chemotherapy, in, 'DS-TL']), verbo([have]), complemento([not, been, firmly, 'established,', the, blasts, of, 'DS-TL', are, sensitive, to, 'low-dose', cytosine, arabinoside])]). relacion([sujeto(['Mouse', gonadal, development, is]), verbo([regulated]), complemento([by, a, variety, of, transcription, factors])]). relacion([sujeto(['Here', we]), verbo([report]), complemento([the, identification, and, characterization, of, a, novel, nuclear, zinc, finger, protein, called, 'GATA', like, 'protein-1', '(', 'GLP-1),', which, is, expressed, at, high, levels, in, the, somatic, cells, of, the, developing, 'gonads,', including, 'Leydig', cells, in, the, testes, and, granulosa, cells, in, the, ovaries])]). relacion([sujeto(['Biochemical', analysis, of, 'GLP-1', shows, that, it]), verbo([acts]), complemento([as, a, transcriptional, repressor, of, 'GATA', factor, function])]). relacion([sujeto(['Loss', of, 'GLP-1']), verbo([leads]), complemento([to, defective, sperm, development, in, males, with, a, marked, reduction, in, mature, spermatids, observed, as, early, as, postnatal, week, 1])]). relacion([sujeto(['In', 'females,']), verbo([loss]), complemento([of, 'GLP-1', leads, to, a, severe, block, in, germ, cell, development, as, early, as, 'E17'])]). relacion([sujeto(['Together,', these, data, identify, 'GLP-1', as, a, critical]), verbo([nuclear]), complemento([repressor, in, somatic, cells, of, the, gonad, that, is, required, for, germ, cell, 'development,', and, highlight, the, importance, of, 'somatic-germ', cell, interactions, in, the, regulation, of, this, critical, process])]). relacion([sujeto(['Whereas', 'Gata2', is, preferentially]), verbo([transcribed]), complemento([early, in, 'hematopoiesis,', elevated, 'GATA-1', levels, result, in, 'GATA-1', occupancy, at, sites, upstream, of, the, 'Gata2', locus, and, transcriptional, repression])]). relacion([sujeto(['GATA-2', occupies, these, sites, in, the, transcriptionally, active, 'locus,']), verbo([suggesting]), complemento([that, a, &, 'quot;GATA', 'switch"', abrogates, 'GATA-2-mediated', positive, autoregulation])]). relacion([sujeto(['Chromatin', immunoprecipitation, '(', 'ChIP)', coupled, with, genomic, microarray, analysis, and, quantitative, 'ChIP', analysis, with, 'GATA-1-null', cells]), verbo([expressing]), complemento([an, estrogen, receptor, ligand, binding, domain, fusion, to, 'GATA-1', revealed, additional, 'GATA', switches, 77, kb, upstream, of, 'Gata2', and, within, intron, 4, at, +, 9.5, kb])]). relacion([sujeto(['GATA-1']), verbo([induced]), complemento([histone, deacetylation, at, and, near, 'Gata2', but, not, at, the, -, 77, kb, region])]). relacion([sujeto(['The', -, 77, kb, 'region,', which, was, 'DNase', 'I', hypersensitive, in, both, active, and, inactive, 'states,']), verbo([conferred]), complemento([equivalent, enhancer, activities, in, 'GATA-1-', and, 'GATA-2-expressing', cells])]). relacion([sujeto(['These', results, indicate, that, dispersed, 'GATA', factor, complexes, function, via, 'long-range', chromatin, interactions, and, qualitatively, distinct, activities, to]), verbo([regulate]), complemento(['Gata2', transcription])]). relacion([sujeto(['We']), verbo([have]), complemento([generated, mice, from, a, 'N-ethyl-N-nitrosourea', mutagenesis, screen, that, carry, a, mutation, in, the, translation, initiation, codon, of, 'Gata-1,', termed, 'Plt13,', which, is, equivalent, to, mutations, found, in, patients, with, acute, megakaryoblastic, leukemia, and, 'Down', syndrome])]). relacion([sujeto(['Adult', 'Gata-1Plt13/+', females, were, not, 'anemic,', but, they, were, thrombocytopenic, and, accumulated, abnormal, megakaryocytes, without, a, concomitant]), verbo([increase]), complemento([in, megakaryocyte, progenitor, cells])]). relacion([sujeto(['The', hematopoietic, 'GATA', factors, 'GATA-1', and, 'GATA-2,', which]), verbo([have]), complemento([distinct, and, overlapping, roles, to, regulate, blood, cell, 'development,', are, reciprocally, expressed, during, erythropoiesis])]). relacion([sujeto(['GATA-1', directly, represses, 'Gata2', 'transcription,', and, reduced, 'GATA-2', synthesis]), verbo([promotes]), complemento([red, blood, cell, development])]). relacion([sujeto(['Gata2', repression]), verbo([involves]), complemento([&, 'quot;GATA', 'switches"', in, which, 'GATA-1', displaces, 'GATA-2', from, 'Gata2', regulatory, regions])]). relacion([sujeto(['We', show, that, extragenic, 'GATA', switch, sites, occupied, by, 'GATA-2']), verbo([associate]), complemento([with, as, much, 'RNA', polymerase, 'II', '(', 'Pol', 'II)', and, basal, transcription, factors, as, present, at, the, active, 'Gata2', promoters])]). relacion([sujeto(['Pol', 'II']), verbo([bound]), complemento([to, 'GATA', switch, sites, in, the, active, locus, was, phosphorylated, on, serine, 5, of, the, 'carboxyl-terminal', 'domain,', indicative, of, elongation, competence])]). relacion([sujeto(['These', results, indicate, that, 'GATA-2-bound', extragenic, regulatory, elements]), verbo([recruit]), complemento(['Pol', 'II,', 'GATA-1', binding, expels, 'Pol', 'II,', and, despite, the, persistent, 'TFIIB-chromatin', 'complexes,', 'Pol', 'II', recruitment, is, blocked])]). relacion([sujeto(['The', development, of, mature, blood, cells, from, hematopoietic, stem, cells, is]), verbo([regulated]), complemento([by, transcription, factors, that, control, and, coordinate, the, expression, of, 'lineage-specific', genes])]). relacion([sujeto(['Among', 'them,', 'GATA-1', is]), verbo([expressed]), complemento([in, 'erythroid,', 'megakaryocytic,', eosinophil, and, mast, cell, 'lineages,', and, 'GATA-2', is, expressed, in, stem, and, progenitor, 'cells,', at, more, immature, stage, compared, with, 'GATA-1'])]). relacion([sujeto(['Based', on, the, characteristic, phenotypes, of, 'GATA-1', and, 'GATA-2', mutant, 'mice,', it]), verbo([has]), complemento([been, suggested, that, mutations, of, these, 'GATA', genes, in, humans, may, result, in, the, onset, of, certain, clinical, diseases])]). relacion([sujeto(['To', 'date,', mutations, of, 'GATA-1', gene]), verbo([have]), complemento([been, found, in, inherited, anemia, and, 'thrombocytopenia,', and, 'Down', 'syndrome-related', acute, 'leukemia,', which, exhibits, megakaryocytic, phenotypes, and, frequently, occurs, in, patients, with, 'Down', syndrome])]). relacion([sujeto(['In', 'contrast,', no, mutation, of, 'GATA-2', gene]), verbo([has]), complemento([been, identified, in, hematological, 'diseases;', 'however,', we, found, the, expression, level, of, 'GATA-2', is, significantly, decreased, in, 'CD34', positive, cells, in, patients, with, aplastic, anemia])]). relacion([sujeto(['Since', 'GATA-2', functions, in, the, proliferation, of, hematopoietic, stem, 'cells,', the, reduction, of, 'GATA-2', expression, in, 'CD34', positive, cells, may, result, in, the]), verbo([decreased]), complemento([number, of, hematopoietic, stem, 'cells,', which, is, the, characteristic, feature, of, aplastic, anemia])]). relacion([sujeto(['The', interactions, of, two, 2, -, mercaptobenzamide, thioester, compounds, with, six, diverse, 'zinc-binding', domains, '(', 'ZBDs)']), verbo([have]), complemento([been, analyzed, by, 'UV/visible', 'spectroscopy,', 'NMR', 'spectroscopy,', and, nucleic, acid, binding, assays])]). relacion([sujeto(['In', all, 'cases,', zinc, ejection]), verbo([led]), complemento([to, a, loss, of, protein, structure])]). relacion([sujeto(['Interestingly,', 'GATA-1', was, resistant, to, reaction, with, the, thioester, compounds, when]), verbo([bound]), complemento([to, its, target, 'DNA', sequence])]). relacion([sujeto(['These', studies, not, only]), verbo([provide]), complemento([information, regarding, the, relative, reactivity, of, cysteine, residues, within, structural, 'ZBDs', but, also, are, crucial, for, the, design, of, future, therapeutic, agents, that, selectively, target, 'ZBDs,', such, as, those, that, occur, in, the, 'HIV-1', nucleocapsid, protein])]). relacion([sujeto(['Developmental', studies, support, a, common, origin, for, blood, and, endothelial, 'cells,', while, studies, of, adult, angiogenic, responses]), verbo([suggest]), complemento([that, the, hematopoietic, system, can, be, a, source, of, endothelial, cells, later, in, life])]). relacion([sujeto(['Here', we, demonstrate, that, expression, of, 'GFPSlp-76', in, a, subset, of, hematopoietic, cells, rescues, this, 'phenotype,', and, that, deficient, cells]), verbo([confer]), complemento([focal, vascular, phenotypes, in, chimeric, embryos, consistent, with, a, 'cell-autonomous', mechanism])]). relacion([sujeto(['Endogenous', 'Syk', and, 'Slp-76,', as, well, as, transgenic, 'GFPSlp-76,', are]), verbo([expressed]), complemento([in, circulating, cells, previously, proposed, to, be, endothelial, 'precursors,', supporting, a, causal, role, for, these, cells])]). relacion([sujeto(['These', studies]), verbo([provide]), complemento([genetic, evidence, for, hematopoietic, contribution, to, vascular, development, and, suggest, that, hematopoietic, tissue, can, provide, a, source, of, vascular, endothelial, progenitor, cells, throughout, life])]). relacion([sujeto(['Vertebrate', 'GATA', transcription, factors]), verbo([have]), complemento([been, classified, into, two, 'subgroups;', 'GATA-1,', 'GATA-2,', and, 'GATA-3', are, expressed, in, hematopoietic, 'cells,', whereas, 'GATA-4,', 'GATA-5,', and, 'GATA-6', are, expressed, in, 'mesoendoderm-derived', tissues])]). relacion([sujeto(['In', 'contrast,', a, 'GATA-4-GATA-1', chimeric, protein, prepared, by, linking, the, 'N-terminal', region, of, 'GATA-4', to, the, 'C-terminal', region, of, 'GATA-1', significantly]), verbo([promoted]), complemento([the, differentiation, and, survival, of, primitive, erythroid, 'cells,', although, this, protein, is, still, insufficient, for, rescuing, 'Gata1'])]). relacion([sujeto(['These', data, thus, show, a, functional, incompatibility, between, hematopoietic, and, endodermal, 'GATA', factors, in, vivo, and]), verbo([provide]), complemento([evidence, indicating, specific, roles, of, the, 'C-terminal', region, of, 'GATA-1', in, primitive, erythropoiesis])]). relacion([sujeto(['Here,', we]), verbo([report]), complemento([that, the, expression, of, these, 'EC', markers, is, initiated, in, the, extraembryonic, region, at, the, 'late-streak', stage, '(', nominal, stage, 'E6'])]). relacion([sujeto(['In', 'contrast,', 'GATA1,', a, marker, for, primitive, erythropoietic, 'progenitors,', is]), verbo([expressed]), complemento([in, a, more, restricted, subset, of, 'Flk1-positive', cells])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, primitive, hematopoietic, cells, arise, from, 'EC', 'marker-positive', cells])]). relacion([sujeto(['Thus,', 'VE-cadherin,', 'PECAM-1,', 'CD34,', 'endoglin,', and, 'Tie2', are]), verbo([expressed]), complemento([not, only, in, adult, and, embryonic, 'ECs', but, in, extraembryonic, 'Flk1-positive', cells, during, gastrulation])]). relacion([sujeto(['The', latter, cell, population, includes, progenitors, that, give, rise, to, primitive, hematopoietic, 'cells,']), verbo([suggesting]), complemento([that, primitive, and, definitive, hematopoietic, cells, in, the, mouse, embryo, arise, from, 'EC', 'marker-positive', cells])]). relacion([sujeto(['Previously,', we]), verbo([reported]), complemento([that, introduction, of, a, transgene, encoding, the, secreted, form, of, rainbow, trout, '(', 'rt)', 'Ea4-peptide', or, human, '(', 'h)', 'Eb-peptide', into, newly, fertilized, eggs, of, medaka, '(', 'Oryzias', 'latipes)', and, zebrafish, '(', 'Danio', 'rerio)', resulted, in, developmental, defects, in, 'heart,', red, blood, cells, and, vasculature])]). relacion([sujeto(['In', addition, to, vasculature, and, red, blood, cell, developmental, 'defects,', multiple, phenocopies, of, heart, developmental, defects, categorized, by, developmental]), verbo([arrest]), complemento([at, 'cardiomyocyte,', heart, tube, and, heart, looping, stages, were, also, observed])]). relacion([sujeto(['Although', a, 'dose-dependent', developmental, defect, in, 'heart,', vasculature, and, red, blood, cells, was, observed, in, embryos, microinjected, with, 'rtEa4-peptide', at, 1.5, and, 2.5, 'hpf,', the, heart, development, in, all, of, the, microinjected, embryos, was]), verbo([arrested]), complemento([at, the, cardiomyocyte, stage])]). relacion([sujeto(['These', results, confirm, our, previous, findings, that, 'rtEa4-', or, 'hEb-peptide', exhibits, pleiotropic, effects, in]), verbo([inhibiting]), complemento(['heart,', vasculature, and, red, blood, cell, development, in, zebrafish, embryos])]). relacion([sujeto(['The', identification, of, short, peptide, tags, that, are, efficiently, biotinylated, by, the, bacterial, 'BirA', biotin, ligase]), verbo([led]), complemento([to, an, approach, for, the, 'single-step', purification, of, transcription, factor, complexes, by, specific, in, vivo, biotinylation, tagging])]). relacion([sujeto(['The', direct]), verbo([binding]), complemento([to, streptavidin, of, biotinylated, 'GATA-1', in, nuclear, extracts, resulted, in, the, 'single-step', capture, of, the, tagged, factor, and, associated, 'proteins,', which, were, eluted, and, identified, by, mass, spectrometry])]). relacion([sujeto(['This']), verbo([led]), complemento([to, the, characterization, of, several, distinct, 'GATA-1', complexes, with, other, transcription, factors, and, chromatin, remodeling, 'cofactors,', which, are, involved, in, activation, and, repression, of, gene, targets])]). relacion([sujeto(['High', 'FGF', activity]), verbo([inhibits]), complemento([primitive, blood, differentiation, and, promotes, endothelial, cell, fate])]). relacion([sujeto(['Conversely,', inhibition, of, 'FGFR', activity]), verbo([leads]), complemento([to, ectopic, blood, formation, and, 'down-regulation', of, endothelial, markers])]). relacion([sujeto(['Expression', and, functional, analyses, indicate, that, 'FGFR2', is, the, key, receptor]), verbo([mediating]), complemento([these, effects])]). relacion([sujeto(['The', 'FGF', pathway]), verbo([regulates]), complemento([primitive, hematopoiesis, by, modulating, 'Gata1', expression, level, and, activity])]). relacion([sujeto(['We', propose, that, the, 'FGF', pathway]), verbo([mediates]), complemento([repression, of, globin, gene, expression, and, that, its, removal, is, essential, before, terminal, differentiation, can, occur])]). relacion([sujeto(['The', 5, '\'', -, 'HS4', chicken, 'beta-globin', insulator, functions, as, a, positional, enhancer, blocker, on, chromatinized, episomes, in, human, 'cells,', blocking, the, 'HS2', enhancer, of, the, human, 'beta-globin', locus, control, region, from]), verbo([activating]), complemento([a, downstream, 'epsilon-globin', gene])]). relacion([sujeto([5, '\'', -, 'HS4', interrupted, formation, of, a, domain, of, histone, 'H3', and, 'H4', acetylation, encompassing, the, 6, -, kb, minilocus, and]), verbo([inhibited]), complemento([transfer, of, 'RNA', polymerase, from, the, enhancer, to, the, gene, promoter])]). relacion([sujeto(['We']), verbo([found]), complemento([that, the, enhancer, blocking, phenotype, was, amplified, when, the, insulated, locus, contained, a, weakened, 'HS2', enhancer, in, which, clustered, point, mutations, eliminated, interaction, of, the, transcription, factor, 'GATA-1'])]). relacion([sujeto(['Nucleosome', depletion, at, 5, '\'', -, 'HS4', was, dependent, on, interaction, of, the, insulator, protein, 'CCCTC-binding', factor, '(', 'CTCF)', and, was]), verbo([required]), complemento([for, enhancer, blocking])]). relacion([sujeto(['These', findings]), verbo([provide]), complemento([evidence, that, a, domain, of, active, chromatin, is, formed, by, spreading, from, an, enhancer, to, a, target, gene, and, can, be, blocked, by, a, 'nucleosome-free', gap, in, an, insulator])]). relacion([sujeto(['The', two, proteins]), verbo([have]), complemento([been, shown, to, function, in, an, antagonistic, 'fashion,', with, 'GATA-1', repressing, 'PU'])]). relacion([sujeto(['It']), verbo([has]), complemento([also, become, clear, that, this, functional, antagonism, involves, direct, interactions, between, the, two, proteins])]). relacion([sujeto(['We']), verbo([have]), complemento([used, a, range, of, biophysical, methods, to, define, the, molecular, details, of, the, 'GATA-1-PU'])]). relacion([sujeto(['Surprisingly,', the, interaction, cannot, be, disrupted, by, single, alanine, substitution, 'mutations,']), verbo([suggesting]), complemento([that, binding, is, distributed, over, an, extended, interface])]). relacion([sujeto(['The', 'C-terminal', basic, tail, region, of, 'CF', appears, to, be, sufficient, to]), verbo([mediate]), complemento([an, interaction, with, 'PU'])]). relacion([sujeto([1]), verbo([interacting]), complemento([motif, from, 'c-Jun,', suggesting, that, 'GATA-1', and, 'c-Jun', might, compete, to, bind, 'PU'])]). relacion([sujeto(['Taken', 'together,', our, data]), verbo([provide]), complemento([a, molecular, perspective, on, the, 'GATA-1-PU'])]). relacion([sujeto([1, 'interaction,', resolving, several, issues, in, the, existing, data, and]), verbo([providing]), complemento([insight, into, the, mechanisms, through, which, these, two, proteins, combine, to, regulate, blood, development])]). relacion([sujeto(['Regulation', of, transcription]), verbo([requires]), complemento([mechanisms, to, both, activate, and, terminate, transcription, factor, activity])]). relacion([sujeto(['GATA-1', is, a, key, haemopoietic, transcription, factor, whose, activity, is]), verbo([increased]), complemento([by, acetylation])]). relacion([sujeto(['We', show, here, that, acetylated, 'GATA-1', is]), verbo([targeted]), complemento([for, degradation, via, the, 'ubiquitin/proteasome', pathway])]). relacion([sujeto(['Acetylation', positively, signals, 'ubiquitination,']), verbo([suggesting]), complemento([that, activation, by, acetylation, simultaneously, marks, 'GATA-1', for, degradation])]). relacion([sujeto(['Promoter-specific', 'MAPK', phosphorylation, then, cooperates, with, acetylation, to]), verbo([execute]), complemento([protein, loss])]). relacion([sujeto(['The', requirement, for, both, modifications, is, novel, and]), verbo([suggests]), complemento([a, way, by, which, degradation, of, the, active, protein, can, be, specifically, regulated, in, response, to, external, 'phosphorylation-mediated', signalling])]). relacion([sujeto(['As', many, transcription, factors, are]), verbo([activated]), complemento([by, 'acetylation,', we, suggest, that, this, might, be, a, general, mechanism, to, control, transcription, factor, activity])]). relacion([sujeto(['Recently,', acquired, mutations, in, the, megakaryocytic, regulator, 'GATA1']), verbo([have]), complemento([been, found, in, essentially, all, cases, of, acute, megakaryoblastic, leukemia, '(', 'AMkL)', in, children, with, 'Down', syndrome, and, in, the, closely, related, malignancy, transient, myeloproliferative, disorder])]). relacion([sujeto(['In', all, 'cases,', mutations, in, 'GATA1']), verbo([lead]), complemento([to, the, expression, of, a, shorter, isoform, of, 'GATA-1,', named, 'GATA-1s'])]). relacion([sujeto(['Because', 'GATA-1s']), verbo([retains]), complemento([both, 'DNA', binding, zinc, 'fingers,', but, is, missing, the, 'N-terminal', transactivation, 'domain,', it, has, been, predicted, that, the, inability, of, 'GATA-1s', to, regulate, its, normal, class, of, megakaryocytic, target, genes, is, the, mechanism, by, which, mutations, in, 'GATA1', contribute, to, the, disease])]). relacion([sujeto(['Indeed,', several, recent]), verbo([reports]), complemento([have, confirmed, that, 'GATA-1s', fails, to, properly, regulate, the, growth, of, megakaryocytic, 'precursors,', likely, through, aberrant, transcriptional, regulation])]). relacion([sujeto(['Although', the, specific]), verbo([target]), complemento([genes, of, 'GATA-1', 'mis-regulated', by, 'GATA-1s', that, drive, this, abnormal, growth, remain, 'undefined,', multiple, candidate, genes, have, been, identified, via, gene, array, studies])]). relacion([sujeto(['Finally,', the, inability, of, 'GATA-1s', to]), verbo([promote]), complemento([expression, of, important, metabolic, 'genes,', such, as, cytadine, 'deaminase,', likely, contributes, to, the, remarkable, hypersensitivity, of, 'AMkL', blasts, to, cytosine, arabinoside])]). relacion([sujeto(['Future', studies, to, define, the, entire, class, of, genes, dysregulated, by, mutations, in, 'GATA1', will]), verbo([provide]), complemento([important, insights, into, the, etiology, of, these, malignancies])]). relacion([sujeto(['We']), verbo([have]), complemento([developed, an, animal, model, to, investigate, the, mechanisms, underlying, an, acute, exacerbation, of, chronic, asthma])]). relacion([sujeto(['Compared', with, animals, receiving, chronic, challenge, 'alone,', mice, in, the, acute, exacerbation, group, exhibited, a, more, marked, inflammatory, 'response,', with, involvement, of, intrapulmonary, airways, and, lung, 'parenchyma,', and]), verbo([increased]), complemento([numbers, of, lymphocytes, and, eosinophils, in, bronchoalveolar, lavage, fluid])]). relacion([sujeto(['They', also, developed, airway, hyperreactivity, '(', 'AHR)', to, 'methacholine,', demonstrable, as]), verbo([increased]), complemento([transpulmonary, resistance, and, decreased, compliance])]). relacion([sujeto(['However,', compared, with, animals, receiving, a, single, 'moderate-level', 'challenge,', inflammation, and, 'AHR', were]), verbo([induced]), complemento([more, rapidly, in, the, acute, exacerbation, group])]). relacion([sujeto(['We', conclude, that, in, mice, with, 'pre-existing', airway, lesions, resembling, mild, chronic, 'asthma,', exposure, to, a, moderately, high, concentration, of, inhaled, antigen]), verbo([induces]), complemento([features, of, an, acute, exacerbation])]). relacion([sujeto(['The', inflammatory, response]), verbo([involves]), complemento([distal, airways, and, is, associated, with, a, distinct, pattern, of, 'AHR,', which, develops, independent, of, the, enhanced, eosinophilic, inflammation])]). relacion([sujeto(['Acquired', somatic, mutations, in, exon, 2, of, the, hematopoietic, transcription, factor, 'GATA-1']), verbo([have]), complemento([been, found, in, individuals, with, 'Down', syndrome, with, both, transient, myeloproliferative, disorder, and, acute, megakaryoblastic, leukemia])]). relacion([sujeto(['These', mutations]), verbo([prevent]), complemento([the, synthesis, of, the, 'full-length', protein, but, allow, the, synthesis, of, its, short, 'isoform,', 'GATA-1s'])]). relacion([sujeto(['Experiments', in, mice]), verbo([suggest]), complemento([that, 'GATA-1s', supports, normal, adult, 'megakaryopoiesis,', platelet, formation, and, erythropoiesis])]). relacion([sujeto(['Here', we]), verbo([report]), complemento([a, 'mutation,', 332, 'G', -, -, &, 'gt;', 'C,', in, exon, 2, of, 'GATA1,', leading, to, the, synthesis, of, only, the, short, isoform, in, seven, affected, males, from, two, generations, of, a, family])]). relacion([sujeto(['Altogether,', data]), verbo([suggest]), complemento([that, 'GATA-1s', 'alone,', produced, in, low, or, normal, 'levels,', is, not, sufficient, to, support, normal, erythropoiesis])]). relacion([sujeto(['Moreover,', this, is, the, first, study, to, indicate, that, a, germline, splicing, mutation, does, not]), verbo([lead]), complemento([to, leukemia, in, the, absence, of, other, cooperating, 'events,', such, as, 'Down', syndrome])]). relacion([sujeto(['We', investigated, the, degree, of, terminal, differentiation, of, splenic, erythroblasts, obtained, from, mice, during, the, acute, phase, of, disease]), verbo([caused]), complemento([by, the, 'anemia-inducing', 'FVAstrain', of, 'Friend', virus])]). relacion([sujeto(['We', also]), verbo([have]), complemento([examined, the, 'Ca2+', 'concentration,', the, distribution, and, amount, of, 'F-actin,', important, cellular, components, such, as, nucleic, 'acids,', 'lipids,', and, 'proteins,', and, the, adhesion, of, precursor, cells, of, 'RBC', at, different, stages, to, vascular, endothelium])]). relacion([sujeto(['These', alternations]), verbo([caused]), complemento([changes, in, biophysical, properties, of, the, 'cell,', such, as, membrane, fluidity, and, deformability])]). relacion([sujeto(['Expression-based', studies, of, multipotential, hematopoietic, progenitor, cells]), verbo([has]), complemento([shown, that, these, cells, express, 'lineage-restricted', genes, from, multiple, lineages, at, low, 'levels,', and, that, they, are, in, effect, '\'', 'primed\'', to, develop, into, all, hematopoietic, cell, types])]). relacion([sujeto(['Expression', profiling, of, oligopotent, and, committed, progenitor, cells]), verbo([has]), complemento([further, shown, that, commitment, to, the, erythroid, lineage, is, associated, with, a, progressive, decline, in, the, number, of, expressed, genes])]). relacion([sujeto(['Lineage', commitment, is]), verbo([regulated]), complemento([by, 'lineage-restricted', transcription, 'factors,', and, studies, show, that, the, erythroid, transcription, factor, 'GATA1,', in, addition, to, activating, a, subset, of, 'genes,', has, global, repressive, effects, on, gene, expression])]). relacion([sujeto(['Terminal', erythroid, differentiation, is]), verbo([associated]), complemento([with, further, reduction, in, the, number, of, expressed, genes])]). relacion([sujeto(['Expression', profiling]), verbo([provides]), complemento([the, means, to, identify, novel, targets, for, the, therapy, of, erythrocytes, 'disorders,', and, to, obtain, insights, into, the, mechanisms, of, cellular, differentiation])]). relacion([sujeto(['In', these, 'patients,', 'AMKL', is]), verbo([associated]), complemento([with, somatic, mutations, in, the, 'X-linked', transcription, factor, 'gene,', 'GATA1'])]). relacion([sujeto(['AMKL', also]), verbo([has]), complemento([been, described, after, 'TMD', in, children, without, 'DS'])]). relacion([sujeto(['We']), verbo([report]), complemento([on, a, 'non-DS', child, identified, with, trisomy, 21, mosaicism, and, a, 'GATA1', mutation, in, the, original, blast, cells, who, has, been, followed, for, 2, years, without, exhibiting, 'AMKL'])]). relacion([sujeto(['The', development, of, embryonic, stem, cell, '(', 'ESC)', therapies]), verbo([requires]), complemento([the, establishment, of, efficient, methods, to, differentiate, 'ESCs', into, specific, cell, lineages])]). relacion([sujeto(['Here,', we]), verbo([report]), complemento([the, in, vitro, differentiation, of, common, marmoset, '(', 'CM)', '(', 'Callithrix', 'jacchus)', 'ESCs', into, hematopoietic, cells, after, exogenous, gene, transfer, using, vesicular, stomatitis, 'virus-glycoprotein-pseudotyped', lentiviral, vectors])]). relacion([sujeto(['By', immunochemical, and, morphological, 'analyses,', we, demonstrated, that, overexpression, of, 'tal1/scl,', but, not, the, remaining, 'genes,', dramatically]), verbo([increased]), complemento([hematopoiesis, of, 'CM', 'ESCs,', resulting, in, multiple, 'blood-cell', lineages])]). relacion([sujeto(['Furthermore,', flow, cytometric, analysis, demonstrated, that, 'CD34,', a, hematopoietic, 'stem/progenitor', cell, 'marker,', was, highly]), verbo([expressed]), complemento([in, 'tal1/scl-overexpressing', embryoid, body, cells])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, transduction, of, exogenous, 'tal1/scl', cDNA, into, 'ESCs', is, a, promising, method, to, induce, the, efficient, differentiation, of, 'CM', 'ESCs', into, hematopoietic, 'stem/progenitor', cells])]). relacion([sujeto(['Peptidase', inhibitor, 3, '(', 'PI3)']), verbo([inhibits]), complemento([neutrophil, elastase, and, 'proteinase-3,', and, has, a, potential, role, in, skin, and, lung, diseases, as, well, as, in, cancer])]). relacion([sujeto(['Genome-wide', expression, profiling, of, chorioamniotic, membranes, revealed]), verbo([decreased]), complemento([expression, of, 'PI3', in, women, with, preterm, premature, rupture, of, membranes])]). relacion([sujeto(['To', elucidate, the, molecular, mechanisms, contributing, to, the]), verbo([decreased]), complemento([expression, in, amniotic, 'membranes,', the, 'PI3', gene, was, searched, for, sequence, variations, and, the, functional, significance, of, the, identified, promoter, variants, was, studied])]). relacion([sujeto(['Putative', transcription, factor]), verbo([binding]), complemento([sites, as, detected, by, in, silico, search, were, verified, by, electrophoretic, mobility, shift, assay, '(', 'EMSA)', using, nuclear, extract, from, 'Hela', and, amnion, cell, nuclear, extract])]). relacion([sujeto(['Eleven', variants, were, in, the, promoter, 'region;', several, putative, transcription, factor]), verbo([binding]), complemento([sites, were, found, at, these, sites, by, database, searches])]). relacion([sujeto(['Differential']), verbo([binding]), complemento([of, transcription, factors, was, demonstrated, at, two, polymorphic, sites, by, electrophoretic, mobility, shift, 'assays,', both, in, amniotic, and, 'HeLa', cell, nuclear, extracts])]). relacion([sujeto(['Differential']), verbo([binding]), complemento([of, the, transcription, factor, 'GATA1', at, -, 689, 'C>G', site, was, confirmed, by, a, supershift])]). relacion([sujeto(['The', promoter, sequences, of, 'PI3']), verbo([have]), complemento([a, high, degree, of, variability])]). relacion([sujeto(['Functional', promoter, variants]), verbo([provide]), complemento([a, possible, mechanism, for, explaining, the, differences, in, 'PI3', mRNA, expression, levels, in, the, chorioamniotic, 'membranes,', and, are, also, likely, to, be, useful, in, elucidating, the, role, of, 'PI3', in, other, diseases])]). relacion([sujeto(['Yisui', 'Shengxue', 'Granules', could, not, only, obviously, improve, the, clinical, symptoms, of, patients, with, 'beta-thalassemia', 'intermedia,', but, also, obviously]), verbo([increased]), complemento([the, contents, of, 'Hb,', 'RBC,', 'HbF', and, 'Ret', '(', 'P<0'])]). relacion([sujeto(['The', expression, levels, of, 'AHSP', and, 'GATA-1', mRNAs, also, significantly]), verbo([increased]), complemento([after, treatment, as, compared, with, those, before, treatment, '(', 'P<0'])]). relacion([sujeto(['The', results, revealed, that, one, of, the, possible, molecular, mechanism, of, the, effects]), verbo([caused]), complemento([by, 'Yisui', 'Shengxue', 'Granules', is, that, it, can, 'up-regulate', the, expression, levels, of, 'AHSP', and, erythroid, transcription, factor, 'GATA-1', 'mRNAs,', enhance, the, protein, synthesis, of, 'AHSP', which, can, bind, the, relative, excess, free, 'alpha-globin,', prevent, the, formation, of, alpha, -, 'globin-cytotoxic', precipitates, in, red, blood, cells, and, decrease, the, hemolysis])]). relacion([sujeto(['We', observed, that]), verbo([binding]), complemento([sites, for, the, ubiquitously, expressed, transcription, factor, 'CP2', were, present, in, regulatory, regions, of, multiple, erythroid, genes])]). relacion([sujeto(['In', these, 'regions,', the, 'CP2']), verbo([binding]), complemento([site, was, adjacent, to, a, site, for, the, erythroid, factor, 'GATA-1'])]). relacion([sujeto(['In', 'particular,', 'CP2']), verbo([binds]), complemento([to, the, 'GATA-1', 'HS2', 'enhancer,', generating, a, ternary, complex, with, 'GATA-1', and, 'DNA'])]). relacion([sujeto(['Chromatin', immunoprecipitation, with, 'K562', cells, showed, that, 'CP2']), verbo([binds]), complemento([in, vivo, to, all, three, regulatory, elements, and, that, both, 'GATA-1', and, 'CP2', were, present, on, the, same, 'GATA-1', and, 'EKLF', regulatory, elements])]). relacion([sujeto(['This', may, contribute, to, the, functional, cooperation, between, these, factors, and]), verbo([provide]), complemento([an, explanation, for, the, important, role, of, ubiquitous, 'CP2', in, the, regulation, of, erythroid, genes])]). relacion([sujeto(['It', is]), verbo([associated]), complemento([with, a, number, of, human, lymphoid, and, epithelial, tumors, and, lymphoproliferative, diseases, in, immunocompromised, patients])]). relacion([sujeto(['A', subset, of, latent, 'EBV', antigens, is]), verbo([required]), complemento([for, immortalization, of, primary, 'B-lymphocytes'])]). relacion([sujeto(['The', metastatic, suppressor, 'Nm23-H1', which, is, downregulated, in, human, invasive, breast, carcinoma, reduces, the, migration, and, metastatic, activity, of, breast, carcinoma, cells, when]), verbo([expressed]), complemento([from, a, heterologous, promoter])]). relacion([sujeto(['Interestingly,', the, 'EBV']), verbo([nuclear]), complemento([antigen, 3, 'C', '(', 'EBNA3C)', reverses, these, activities, of, 'Nm23-H1'])]). relacion([sujeto(['The', alpha, 'V', integrins]), verbo([recognize]), complemento([a, variety, of, ligands, for, signaling, and, are, involved, in, cell, migration, and, proliferation, and, also, serve, as, major, receptors, for, 'extracellular-matrix-mediated', cell, adhesion, and, migration])]). relacion([sujeto(['The', goal, of, this, study, was, to, determine, if, 'Nm23-H1', and, 'EBNA3C', can]), verbo([modulate]), complemento([alpha, 'V', integrin, expression, and, downstream, activities])]). relacion([sujeto(['Furthermore,', the, study, showed, that, the, association, of, the, 'Sp1', and, 'GATA', transcription, factors, with, 'Nm23-H1', is]), verbo([required]), complemento([for, modulation, of, the, alpha, 'V', integrin, activity])]). relacion([sujeto(['Thus,', these, results]), verbo([suggest]), complemento([a, direct, correlation, between, the, alpha, 'V', integrin, expression, and, the, interaction, of, 'Nm23-H1', with, 'EBNA3C'])]). relacion([sujeto(['It']), verbo([has]), complemento([been, reported, that, somatic, mutations, in, the, 'X-linked', 'GATA1', gene, are, present, in, hematological, clonal, disorders, in, children, with, 'Down', syndrome, '(', 'DS)'])]). relacion([sujeto(['We']), verbo([have]), complemento([overexpressed, 'VEGF122', or, 'VEGF170,', which, are, equivalent, to, mouse, 'VEGF120', and, 'VEGF164,', in, developing, 'Xenopus', embryos])]). relacion([sujeto(['These', results]), verbo([suggested]), complemento([both, that, injection, of, 'VEGF170', resulted, in, disturbance, of, vasculogenesis, in, the, posterior, portion, of, the, blood, 'island,', with, excessive, production, of, endothelial, cells, at, the, expense, of, blood, 'cells,', and, that, the, anterior, and, posterior, portions, of, the, 'VBI', may, have, distinct, characteristics])]). relacion([sujeto(['When', exposed, to, a, 'pathogen,', a, naive, 'CD4(+)', 'T', cell, is, forced, to, make, a, cell, fate, decision, that]), verbo([leads]), complemento([to, a, polarized, population, of, 'Th1', 'IFN-gamma-', or, 'Th2', 'IL-4-', producing, cells])]). relacion([sujeto(['Although', 'IL-4']), verbo([has]), complemento([traditionally, been, considered, a, factor, that, promotes, 'Th2', cell, 'differentiation,', recent, evidence, has, demonstrated, that, the, site, and, timing, of, 'IL-4', expression, in, an, immune, response, determines, its, ultimate, effects, on, 'CD4(+)', 'T', cell, fate])]). relacion([sujeto(['Using', a, mast, cell, '(', 'MC)', reconstitution, 'model,', we, demonstrate, that, 'MC-derived', 'IL-4']), verbo([promoted]), complemento(['Th1', responses, in, vivo])]). relacion([sujeto(['The', hierarchy, of, 'IL-4', expression, potential, was, directly]), verbo([associated]), complemento([with, the, degree, of, basal, chromatin, accessibility, at, 'cis-regulatory', elements, conserved, noncoding, 'sequence-1', and, 'V(A)', enhancer, within, the, 'Th2', locus])]). relacion([sujeto(['GATA1/2', and, 'Ikaros,', factors, with, opposing, roles, in, chromatin, 'remodeling,']), verbo([acted]), complemento([at, these, sites])]). relacion([sujeto(['We', propose, that, 'GATA', and, 'Ikaros', proteins, coordinately, 'fine-tune', accessibility, at, the, 'Il4', locus, during, development, to, variably]), verbo([regulate]), complemento(['IL-4', expression])]). relacion([sujeto(['Failure', to, specify, the, cytologic, origin, of, the, stromal, cell]), verbo([has]), complemento([precluded, the, development, of, nonsurgical, therapies, and, limits, understanding, of, its, basic, biology])]). relacion([sujeto(['We']), verbo([report]), complemento([that, the, stromal, cells, express, proteins, '(', 'Scl,', 'brachyury,', 'Csf-1R,', 'Gata-1,', 'Flk-1,', and, 'Tie-2)', that, characterize, embryonic, progenitor, cells, with, hemangioblastic, differentiation, potential, and, conclude, that, embryonic, progenitors, with, hemangioblast, potential, represent, a, possible, cytologic, equivalent, of, the, stromal, cell])]). relacion([sujeto(['We', also, identified, a, new, 'autocrine/paracrine', stimulatory, loop, between, the, receptor, 'Tie-2', and, the, 'hypoxia-inducible', factor]), verbo([target]), complemento(['Ang-1,', 'which,', combined, with, previous, 'observations,', suggests, that, a, variety, of, autocrine, loops, may, be, initiated, in, 'hemangioblastomas,', depending, on, the, differentiation, status, of, the, tumor, cells, and, the, extent, of, 'HIF', downstream, activation])]). relacion([sujeto(['The', 'lineage-determining', transcription, factor, 'CCAAT', enhancer]), verbo([binding]), complemento([protein, alpha, '(', 'C/EBPalpha)', is, required, for, myeloid, differentiation])]). relacion([sujeto(['Decreased', function, or, expression, of, 'C/EBPalpha', is, often]), verbo([found]), complemento([in, human, acute, myeloid, leukemia])]). relacion([sujeto(['However,', the, precise, impact, of, 'C/EBPalpha', deficiency, on, the, maturation]), verbo([arrest]), complemento([in, leukemogenesis, is, not, well, understood])]). relacion([sujeto(['The', expression, of, 'bcr/abl', in, 'C/EBPalphapos', fetal, liver, cells]), verbo([led]), complemento([to, a, chronic, myeloid, 'leukemia-like', disease])]). relacion([sujeto(['Surprisingly,', 'bcr/abl-expressing', 'C/EBPalpha-/-', fetal, liver, cells, failed, to]), verbo([induce]), complemento([a, myeloid, disease, in, transplanted, 'mice,', but, caused, a, 'fatal,', transplantable, erythroleukemia, instead])]). relacion([sujeto(['Accordingly,']), verbo([increased]), complemento([expression, of, the, transcription, factors, 'SCL', and, 'GATA-1', in, hematopoietic, precursor, cells, of, 'C/EBPalpha-/-R01-EY-11298', ')', fetal, livers, was, found])]). relacion([sujeto(['Id1,', an, inhibitor, of, erythroid, 'differentiation,', was, identified, as, a, critical, direct]), verbo([target]), complemento([of, 'C/EBPalpha'])]). relacion([sujeto(['Taken', 'together,', our, study]), verbo([provides]), complemento([evidence, that, myeloid, lineage, identity, of, malignant, hematopoietic, progenitor, cells, requires, the, residual, expression, of, 'C/EBPalpha'])]). relacion([sujeto(['Specification', and, differentiation, of, the, megakaryocyte, and, erythroid, lineages, from, a, common, bipotential, progenitor]), verbo([provides]), complemento([a, well, studied, model, to, dissect, binary, cell, fate, decisions])]). relacion([sujeto(['To', understand, how, the, distinct, 'megakaryocyte-', and, 'erythroid-specific', gene, programs, 'arise,', we]), verbo([have]), complemento([examined, the, transcriptional, regulation, of, the, megakaryocyte, erythroid, transcription, factor, 'GATA1'])]). relacion([sujeto(['Hemopoietic-specific', mouse, '(', 'm)GATA1', expression]), verbo([requires]), complemento([the, mGata1, enhancer, 'mHS-3'])]). relacion([sujeto([5, are]), verbo([required]), complemento([for, megakaryocyte, but, not, red, cell, expression])]). relacion([sujeto([5]), verbo([binds]), complemento([key, hemopoietic, transcription, factors, in, vivo, and, is, required, to, maintain, histone, acetylation, at, the, mGata1, locus, in, primary, megakaryocytes])]). relacion([sujeto(['In', vitro, three, 'DNA']), verbo([binding]), complemento([activities, 'A,', 'B,', and, 'C', bind, to, the, core, of, the, 25, -, bp, 'element,', and, these, binding, sites, are, conserved, through, evolution])]). relacion([sujeto(['Activity', 'A', is, the, zinc, finger, transcription, factor, 'ZBP89', that, also]), verbo([binds]), complemento([to, other, cis, elements, in, the, mGata1, locus])]). relacion([sujeto(['Furthermore,', mutation, analysis, in, transgenic, mice]), verbo([reveals]), complemento([activity, 'B', is, required, for, 'megakaryocyte-specific', enhancer, function])]). relacion([sujeto(['Bioinformatic', analysis, shows, sequence, corresponding, to, the]), verbo([binding]), complemento([site, for, activity, 'B', is, a, previously, unrecognized, 'motif,', present, in, the, cis, elements, of, the, 'Fli1', 'gene,', another, important, 'megakaryocyte-specific', transcription, factor])]). relacion([sujeto(['In', 'summary,', we]), verbo([have]), complemento([identified, a, motif, and, a, 'DNA', binding, activity, likely, to, be, important, in, directing, a, megakaryocyte, gene, expression, program, that, is, distinct, from, that, in, red, cells])]). relacion([sujeto(['GATA-1,', a, zinc, finger, transcription, 'factor,']), verbo([has]), complemento([been, believed, to, be, indispensable, for, the, survival, of, proerythroblasts])]). relacion([sujeto(['However,', we]), verbo([found]), complemento([that, 'GATA-1-null', proerythroblasts, could, survive, and, proliferate, on, 'OP9', stroma, cells, in, the, presence, of, erythropoietin])]). relacion([sujeto(['Furthermore,', myeloid, and, mast, cells, were]), verbo([induced]), complemento([from, the, 'GATA-1-null', proerythroblasts, by, the, stimulation, of, 'granulocyte-macrophage', 'colony-stimulating', factor, '(', 'GM-CSF)', and, 'interleukin-3', '(', 'IL-3),', 'respectively,', but, lymphoid, differentiation, was, not, achieved, by, in, vivo, transfer])]). relacion([sujeto(['Thus,', without, activity, of, the, transcription, factor]), verbo([required]), complemento([for, terminal, 'differentiation,', even, relatively, mature, and, committed, cells, proliferate, continuously, with, the, differentiation, capacity, to, other, lineages])]). relacion([sujeto(['Our', data]), verbo([suggest]), complemento([that, 'GATA-1', is, a, critical, transcription, factor, to, fix, erythroid, progenitors, to, the, erythroid, lineage])]). relacion([sujeto(['Human', acute, myeloid, leukemias, with, the, 't(8;21)', translocation]), verbo([express]), complemento([the, 'AML1-ETO', fusion, protein, in, the, hematopoietic, stem, cell, compartment, and, show, impairment, in, erythroid, differentiation])]). relacion([sujeto(['This', clinical]), verbo([finding]), complemento([is, reproduced, in, multiple, murine, and, cell, culture, model, systems, in, which, 'AML1-ETO', specifically, interferes, with, erythroid, maturation])]). relacion([sujeto(['Using', purified, normal, human, early, hematopoietic, progenitor, 'cells,', we]), verbo([find]), complemento([that, 'AML1-ETO', impedes, the, earliest, discernable, steps, of, erythroid, lineage, commitment])]). relacion([sujeto(['Furthermore,', the, 'E1A-GATA-1', 'fusion,', but, not, 'wild-type', 'GATA-1,', rescues, erythroid, lineage, commitment, in, primary, human, progenitors]), verbo([expressing]), complemento(['AML1-ETO'])]). relacion([sujeto(['Erythroid', progenitors]), verbo([have]), complemento([the, potential, to, proliferate, rapidly, in, response, to, environmental, stimuli])]). relacion([sujeto(['This', was, achieved, by, our, development, of, a, noninvasive, 'real-time', monitoring, system, for, erythropoiesis, using, transgenic, mouse, lines]), verbo([expressing]), complemento([luciferase, under, the, control, of, the, mouse, 'Gata1', hematopoietic, regulatory, domain, '(', 'G1-HRD-luc)', or, human, 'beta-globin', locus, control, region, '(', 'Hbb-LCR-luc)'])]). relacion([sujeto(['Optical', bioluminescence, images, revealed, that, the, luciferase, was, specifically]), verbo([expressed]), complemento([in, spleen, and, bone, marrow, and, was, induced, rapidly, in, response, to, anemia, and, hypoxia, stimuli])]). relacion([sujeto(['Increased', plasma, 'EPO', concentration, preceded, an]), verbo([increase]), complemento([in, 'G1-HRD-luc,', supporting, our, contention, that, 'EPO', acts, as, the, key, upstream, signal, in, stress, erythropoiesis])]). relacion([sujeto(['Hence,', we, conclude, that, 'G1-HRD-luc', and, 'Hbb-LCR-luc', reporters, are, differentially]), verbo([activated]), complemento([during, stress, erythropoiesis, and, that, the, transgenic, mouse, lines, used, serve, as, an, important, means, for, understanding, the, homeostatic, regulation, of, erythropoiesis])]). relacion([sujeto(['Recent', studies]), verbo([have]), complemento([suggested, that, endogenous, erythropoietin, '(', 'Epo)', plays, an, important, role, in, the, mobilization, of, bone, 'marrow-derived', endothelial, progenitor, cells, '(', 'EPCs)'])]). relacion([sujeto(['Hypoxia']), verbo([enhanced]), complemento([the, expression, of, 'EpoR', on, pulmonary, endothelial, cells, in, 'wild-type', but, not, 'EpoR(-/-)', rescued, mice])]). relacion([sujeto(['Finally,', hypoxia]), verbo([activated]), complemento([endothelial, nitric, oxide, synthase, in, the, lungs, in, 'wild-type', mice, but, not, in, 'EpoR(-/-)', rescued, mice])]). relacion([sujeto(['These', results, indicate, that, the, endogenous, 'Epo/EpoR', system, plays, an, important, role, in, the, recruitment, of, 'EPCs', and]), verbo([prevents]), complemento([the, development, of, 'PH', during, chronic, hypoxia, in, mice, in, 'vivo,', suggesting, the, therapeutic, importance, of, the, system, for, the, treatment, of, 'PH'])]). relacion([sujeto(['In', separate, expression, pattern, and, 'micro-array', screens, the, zinc, finger, containing, 'factor,', 'znfl2,']), verbo([has]), complemento([been, previously, implicated, in, hematopoiesis])]). relacion([sujeto([znfl2, expression, in, the, hematopoietic, intermediate, mesoderm, and, derived, erythrocytes]), verbo([required]), complemento([early, genes, cloche, and, 'spadetail,', but, not, gata1])]). relacion([sujeto(['Expression', was, 'up-regulated', in, scl, 'gain-of-function', 'embryos,', identifying, znfl2, as, an, early, erythroid, factor, that, is]), verbo([regulated]), complemento([upstream, or, independently, of, gata1])]). relacion([sujeto(['Furthermore,', we, identified, a, duplicate, znfl2, gene, in, the, genome, '(', 'znfl2b)', which, was]), verbo([expressed]), complemento([in, early, mesendoderm, and, weakly, in, the, lateral, plate, 'mesoderm,', overlapping, in, expression, with, znfl2])]). relacion([sujeto(['The', production, of, 'loss-of-function', models, for, 'znfl2,', znfl2b, and, 'znfl2/znfl2b', together]), verbo([suggested]), complemento([that, these, erythrocyte, specific, zinc, finger, genes, are, dispensible, for, erythropoiesis])]). relacion([sujeto(['The', transcription, factor, scl]), verbo([acts]), complemento([upstream, of, both, gata1, and, pu])]). relacion([sujeto([1, in, these, precursor, 'pools,']), verbo([activating]), complemento([a, series, of, conserved, transcription, factors, that, 'cell-autonomously', specify, either, myeloid, or, erythroid, fates])]). relacion([sujeto(['We', show, here, that, the, 'Bmp', receptor, 'lost-a-fin/alk8', is]), verbo([required]), complemento([for, rostral, pu])]). relacion([sujeto(['Introducing', a, constitutively, active, version, of, the, 'Alk8', receptor]), verbo([led]), complemento([to, increased, pu])]). relacion([sujeto(['The', 'Crim1', gene, encodes, a, transmembrane, protein, containing, six, 'cysteine-rich', repeats, similar, to, those]), verbo([found]), complemento([in, the, 'BMP', 'antagonist,', chordin, '(', 'chd)'])]). relacion([sujeto(['To', investigate, its, physiological, 'role,', zebrafish, crim1, was, cloned, and, shown, to, be, both, maternally, and, zygotically]), verbo([expressed]), complemento([during, zebrafish, development, in, sites, including, the, 'vasculature,', intermediate, cell, 'mass,', 'notochord,', and, otic, vesicle])]). relacion([sujeto(['This', was, accompanied, by, a]), verbo([loss]), complemento([of, muscle, pioneer, cells])]). relacion([sujeto(['Analysis', of, the, crim1, morphant, phenotype, in, 'Tg(fli:EGFP)', fish, showed, a, clear, reduction, in, the, endothelial, cells, forming, the, intersegmental, vessels, and, a]), verbo([loss]), complemento([of, the, dorsal, longitudinal, anastomotic, vessel, '(', 'DLAV)'])]). relacion([sujeto(['Cell-type-specific', transcription, of, mouse, 'high-affinity', 'IgE', receptor, '(', 'FcepsilonRI)', 'beta-chain', is, positively]), verbo([regulated]), complemento([by, the, transcription, factor, 'GATA-1'])]). relacion([sujeto(['Although', 'GATA-1', is]), verbo([expressed]), complemento([in, erythroid, 'cells,', 'megakaryocytes,', and, mast, 'cells,', the, expression, of, mouse, 'FcepsilonRI', 'beta-chain', is, restricted, to, mast, cells])]). relacion([sujeto(['A', transient, reporter, assay, demonstrated, that, the, 'beta-chain', promoter, functioned, in, 'PT18', but, not, in, 'Ba/F3', and, that, the, transcription, activity, of, the, 'beta-chain', promoter, in, 'PT18', was, markedly]), verbo([suppressed]), complemento([by, overexpression, of, 'FOG-1'])]). relacion([sujeto(['Although', the, activity, of, the, 'beta-chain', 'promoter,', which, was, upregulated, by, coexpression, of, 'GATA-1,', was, significantly]), verbo([suppressed]), complemento([by, coexpression, of, 'FOG-1', in, the, simian, kidney, 'CV-1', cells, '(', 'beta-chain(-),', 'GATA-1(-),', and, 'FOG-1(-)),', the, transactivation, of, the, 'beta-chain', promoter, by, the, 'GATA-1', mutant, 'V205G,', which, cannot, bind, 'FOG-1,', was, not, affected, by, coexpression, of, 'FOG-1'])]). relacion([sujeto(['Further,', overexpression, of, 'FOG-1', in, 'PT18', resulted, in]), verbo([decreases]), complemento([in, cell, surface, expression, of, 'FcepsilonRI', and, 'beta-chain', transcription])]). relacion([sujeto(['Finally,', suppression, of, 'FOG-1', expression, using, an, siRNA, approach, resulted, in]), verbo([increased]), complemento(['beta-chain', promoter, activity, in, 'Ba/F3'])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, 'FOG-1', expression, level, regulates, the, 'GATA-1-dependent', 'FcepsilonRI', 'beta-chain', promoter])]). relacion([sujeto(['To']), verbo([gain]), complemento([insight, into, gene, expression, differences, in, 'AMKL,', we, compared, 24, 'DS', and, 39, 'non-DS', 'AMKL', samples])]). relacion([sujeto(['We']), verbo([found]), complemento([that, 'non-DS-AMKL', samples, cluster, in, two, 'groups,', characterized, by, differences, in, expression, of, 'HOX/TALE', family, members])]). relacion([sujeto(['To', explore, alterations, of, the, 'GATA1', 'transcriptome,', we, used, 'cross-species', comparison, with, genes]), verbo([regulated]), complemento([by, 'GATA1', expression, in, murine, erythroid, precursors])]). relacion([sujeto(['Genes', repressed, after, 'GATA1', induction, in, the, murine, 'system,', most, notably, 'GATA-2,', 'MYC,', and, 'KIT,', show]), verbo([increased]), complemento([expression, in, 'DS-AMKL,', suggesting, that, 'GATA1s', fail, to, repress, this, class, of, genes])]). relacion([sujeto(['Only', a, subset, of, genes, that, are, 'up-regulated', upon, 'GATA1', induction, in, the, murine, system, show]), verbo([increased]), complemento([expression, in, 'DS-AMKL,', including, 'GATA1', and, 'BACH1,', a, probable, negative, regulator, of, megakaryocytic, differentiation, located, on, chromosome, 21])]). relacion([sujeto(['Our', results, identify, relevant, signatures, for, distinct, 'AMKL', entities, and]), verbo([provide]), complemento([insight, into, gene, expression, changes, associated, with, these, related, leukemias])]). relacion([sujeto(['Although', biochemical, features, of, heme, synthesis, enzymes]), verbo([have]), complemento([been, well, 'characterized,', the, function, of, these, enzymes, in, early, embryogenesis, is, not, fully, understood])]). relacion([sujeto(['We']), verbo([found]), complemento([that, the, sixth, heme, synthesis, 'enzyme,', coproporphyrinogen, oxidase, '(', 'CPO),', is, predominantly, expressed, in, the, intermediate, cell, mass, '(', 'ICM)', that, is, a, major, site, of, zebrafish, primitive, hematopoiesis])]). relacion([sujeto(['Knockdown', of, zebrafish, 'CPO', using, 'anti-sense', morpholinos, '(', 'CPO-MO)']), verbo([leads]), complemento([to, a, significant, suppression, of, hemoglobin, production, without, apparent, reduction, of, blood, cells])]). relacion([sujeto(['Furthermore,', expression, of, 'CPO', in, the, 'ICM', is, severely]), verbo([suppressed]), complemento([in, both, vlad, 'tepes/gata1', mutants, and, in, 'biklf-MO-injected', embryos])]). relacion([sujeto(['In', 'contrast,', 'over-expression', of, biklf, and, gata1, significantly]), verbo([induces]), complemento([ectopic, 'CPO', expression])]). relacion([sujeto(['The', function, of, 'CPO', in, heme, biosynthesis, is, apparently]), verbo([conserved]), complemento([between, zebrafish, and, 'human,', suggesting, that, 'CPO-MO-injected', zebrafish, embryos, might, be, a, useful, in, vivo, assay, system, to, measure, the, biological, activity, of, human, 'CPO', mutations])]). relacion([sujeto(['Exposure', to, ethanol, during, human, embryonic, period]), verbo([has]), complemento([severe, teratogenic, effects, on, the, cardiovascular, system])]). relacion([sujeto(['The', effective, concentration, to]), verbo([cause]), complemento([50, '%', malformations, '(', 'EC50)', was, 182.5, 'mmol/L'])]). relacion([sujeto(['It', is]), verbo([found]), complemento([that, 400, 'mmol/L', ethanol, pulse, exposure, can, induce, circulatory, defects, in, 43, '%', treated, embryos])]). relacion([sujeto(['By', employing, in, situ, hybridization, with, endothelial, biomarker, '(', 'Flk-1),', we, revealed, that, ethanol, disrupts, the, establishment, of, trunk, axial, 'vasculature,', but]), verbo([has]), complemento([no, effect, on, cranial, vessels])]). relacion([sujeto(['Combined', with, the, results, of, 'semi-thin', histological, 'sections,', the, in, situ, hybridization, experiments, with, arterial, and, venous, biomarkers, '(', 'ephrinB2,', 'ephB4)']), verbo([suggested]), complemento([that, ethanol, mainly, interrupts, the, development, of, dorsal, aorta, while, has, little, effect, on, axial, vein])]). relacion([sujeto(['These', results]), verbo([provide]), complemento([important, clues, to, the, study, of, adverse, effects, of, ethanol, on, the, cardiovascular, development, in, human, fetus])]). relacion([sujeto(['Erythroid', differentiation]), verbo([involves]), complemento([the, transcription, factor, 'GATA-1', that, positively, regulates, promoters, of, erythroid, genes, '(', including, 'haemoglobin,', 'glycophorin,', erythropoietin, 'receptor)', and, of, erythropoietin])]). relacion([sujeto(['Upon', erythropoietin, starvation, or, engagement, of, the, death, receptor, 'Fas,', caspases, are]), verbo([activated]), complemento([in, erythroid, precursors, and, cleave, 'GATA-1,', thus, inducing, maturation, arrest, and, apoptosis, of, immature, erythroblasts])]). relacion([sujeto(['We']), verbo([have]), complemento([recently, demonstrated, 'that,', upon, erythropoietin, 'stimulation,', 'caspase-3', was, also, 'activated,', an, event, required, for, human, terminal, erythroblast, maturation])]). relacion([sujeto(['Proteins', cleaved, by, caspases, in, erythroid, cells, undergoing, terminal, differentiation, include, 'Lamin', 'B', and, 'Acinus,', which, are]), verbo([involved]), complemento([in, chromatin, condensation])]). relacion([sujeto(['Therefore,', there, are, some, mechanisms, underlying, the, selective, protection, of, 'caspase-3']), verbo([targets]), complemento([during, erythropoiesis])]). relacion([sujeto(['This', model, in, which, caspases, activation, is]), verbo([required]), complemento([for, differentiation, may, apply, to, other, haematopoietic, or, non, haematopoietic, cellular, systems, which, are, described, in, this, review])]). relacion([sujeto(['In', a, mouse, experimental, asthma, 'model,', the, administration, of, bacterial, lipopolysaccharide, '(', 'LPS),', particularly, at, low, 'doses,']), verbo([enhances]), complemento([the, levels, of, ovalbumin, '(', 'OVA)-induced', eosinophilic, airway, inflammation])]). relacion([sujeto(['In', an, effort, to, clarify, the, cellular, and, molecular, basis, for, the, 'LPS', 'effect,', we, demonstrate, that, the, 'OVA-induced', eosinophilic, inflammation, in, the, lung, is, dramatically]), verbo([increased]), complemento([by, the, administration, of, 'LPS', in, 'wild-type', 'mice,', whereas, such, increase, was, not, observed, in, 'mast-cell-deficient', mice, or, 'Toll-like', receptor, '(', 'TLR)4-deficient', mice])]). relacion([sujeto(['Adoptive', transfer, of, 'bone-marrow-derived', mast, cells, '(', 'BMMCs)', from, 'wild-type,', but, not, from, 'TLR4-deficient,', mice, restored, the]), verbo([increased]), complemento([eosinophilic, inflammation, in, 'mast-cell-deficient', mice])]). relacion([sujeto(['Moreover,', in, vitro, analysis, revealed, that, the, treatment, of, 'BMMCs', with, 'LPS', resulted, in, 'NF-kappaB', 'activation,', sustained, 'up-regulation', of, 'GATA1', and, -, 2, 'expression,', and]), verbo([increased]), complemento([the, capability, to, produce, 'IL-5', and, -, 13])]). relacion([sujeto(['Dramatic']), verbo([increases]), complemento([in, the, expression, of, 'IL-5', and, -, 13, and, 'Eotaxin', 2, were, detected, in, 'LPS-treated', 'BMMCs', after, costimulation, with, 'LPS', and, 'IgE/Ag'])]). relacion([sujeto(['Overexpression', of, 'GATA1,', but, not, 'GATA2,', in, 'MC9', mast, cells, resulted, in]), verbo([increased]), complemento([transcriptional, activity, of, 'IL-4,', -, 5, ',', and, -, 13])]). relacion([sujeto(['Furthermore,', the, levels, of, transcription, of, 'Th2', cytokines, in, 'BMMCs', were]), verbo([decreased]), complemento([by, the, introduction, of, small, interfering, 'RNA', for, 'GATA1'])]). relacion([sujeto(['Thus,', mast, cells, appear, to, control, allergic, airway, inflammation, after, their, activation, and, modulation, through, 'TLR4-mediated', induction, of, 'GATA1', and, subsequent]), verbo([increase]), complemento([in, 'Th2', cytokine, production])]). relacion([sujeto(['Hemgn', '(', a, gene, symbol, for, hemogen, in, 'mouse,', 'EDAG', in, human, and, 'RP59', in, 'rat)', encodes, a]), verbo([nuclear]), complemento([protein, that, is, highly, expressed, in, hematopoietic, tissues, and, acute, leukemia])]). relacion([sujeto(['To', characterize, its, regulatory, 'mechanisms,', we, examined, the, activities, of, a, 'Hemgn', promoter, containing, 2975, bp, of, 5, '\'', flanking, sequence, and, 196, bp, of, 5, '\'', untranslated, region, '(', 5, '\'', 'UTR)', sequence, both, in, vitro, and, in, 'vivo:', this, promoter, is, preferentially]), verbo([activated]), complemento([in, a, hematopoietic, cell, 'line,', not, in, nonhematopoietic, cell, 'lines,', and, is, sufficient, to, drive, the, transcription, of, a, lacZ, transgene, in, hematopoietic, tissues, in, transgenic, mice])]). relacion([sujeto(['Mutagenesis', analyses, showed, that, the, 5, '\'', 'UTR', including, two, highly]), verbo([conserved]), complemento(['GATA', boxes, is, critical, for, the, promoter, activity])]). relacion([sujeto(['GATA1,', not, 'GATA2,']), verbo([binds]), complemento([to, the, 'GATA', binding, sites, and, transactivates, the, 'Hemgn', promoter, in, a, 'dose-dependent', manner])]). relacion([sujeto(['This', study]), verbo([suggests]), complemento([that, the, 'Hemgn', promoter, contains, critical, regulatory, elements, for, its, transcription, in, hematopoietic, tissues, and, 'Hemgn', is, a, direct, target, of, 'GATA1', in, leukemia, cells])]). relacion([sujeto(['Currently', available, 'systems,', 'however,', often]), verbo([have]), complemento([limited, in, vivo, functionality, because, of, 'leakiness,', insufficient, levels, of, 'induction,', lack, of, tissue, specificity, or, prohibitively, complicated, designs])]). relacion([sujeto(['This', system]), verbo([has]), complemento([great, robustness, and, 'versatility,', governing, tightly, controlled, gene, expression, in, cell, 'lines,', in, embryonic, or, hematopoietic, stem, 'cells,', in, human, tumors, xenotransplanted, into, nude, 'mice,', in, the, brain, of, rats, injected, intraparenchymally, with, the, 'vector,', and, in, transgenic, mice, generated, by, infection, of, fertilized, oocytes])]). relacion([sujeto(['The', transcriptional, regulation, of, the, human, reduced, folate, carrier, '(', 'hRFC),']), verbo([involved]), complemento([in, cellular, uptake, of, methotrexate, and, reduced, 'folates,', was, studied, in, childhood, acute, lymphoblastic, leukemia, '(', 'ALL)'])]). relacion([sujeto(['The', hRFC, gene, is]), verbo([regulated]), complemento([by, six, noncoding, exons, '(', 'A1/A2', and, 'A', to, 'E)', and, multiple, promoters])]). relacion([sujeto(['For', the, 'xenografts,', gel, shift, and, chromatin, immunoprecipitation, assays, assessed, transcription, factor]), verbo([binding]), complemento([to, the, 'hRFC-A1/A2', and, 'hRFC-B', promoters])]). relacion([sujeto(['By', chromatin, immunoprecipitation, and, gel, shift, 'assays,']), verbo([binding]), complemento([was, confirmed, for, 'USF1', and, 'GATA1', for, 'hRFC-A1/A2,', and, for, 'Sp1,', 'USF1,', and, 'Ikaros', for, 'hRFC-B'])]). relacion([sujeto(['Our', results, show, a, complex, regulation, of, hRFC, in, 'ALL']), verbo([involving]), complemento([the, 'hRFC-A1/A2', and, 'hRFC-B', promoters, and, noncoding, exons])]). relacion([sujeto(['The', 'Myb', 'proto-oncogene', encodes, a, transcription, factor, '(', 'c-Myb)', that, is, essential, for, normal, hematopoiesis, and, is, thought, to]), verbo([regulate]), complemento([hematopoietic, cell, proliferation, and, differentiation, by, regulating, expression, of, specific, target, genes])]). relacion([sujeto(['We', identify, the, mouse, 'erythroid-specific', carbonic, anhydrase, 'I', promoter, '(', 'CAIe)', as, a]), verbo([target]), complemento([of, 'c-Myb', activity, and, demonstrate, that, 'Myb', activity, is, critical, for, carbonic, anhydrase, 'I', '(', 'CAI)', expression, in, 'C19', 'MEL', cells])]). relacion([sujeto(['Coexpression', of, 'GATA-1', with, 'c-Myb', results, in, synergistic, activation, of, transcription, from, the, 'CAIe', promoter, and, both, transcription, factors]), verbo([interact]), complemento([with, the, 'CAIe', promoter, in, vivo])]). relacion([sujeto(['We', identify, a, novel, 20, bp, sequence, in, the, 'CAIe', promoter, that, is, sufficient, to]), verbo([mediate]), complemento([synergistic, activation, of, the, 'CAIe', promoter, by, 'c-Myb', and, 'GATA-1'])]). relacion([sujeto(['c-Myb', and, 'GATA-1']), verbo([interact]), complemento([with, this, 'DNA', sequence, suggesting, that, 'c-Myb', and, 'GATA-1', may, be, contained, in, a, complex, that, interacts, with, this, region, of, the, 'CAIe', promoter])]). relacion([sujeto(['Forced', expression, of, 'CAI', delayed, 'HMBA-induced', differentiation, of, 'MEL', cells, and]), verbo([maintained]), complemento([them, in, a, proliferating, state])]). relacion([sujeto(['These', data, strongly]), verbo([suggest]), complemento([that, 'CAI', is, a, 'c-Myb', target, and, is, involved, in, regulating, 'MEL', cell, proliferation, and, differentiation])]). relacion([sujeto(['Sertoli', cell, number, is, considered, to, be, stable, and, unmodifiable, by, hormones, after, puberty, in, 'mammals,', although, recent, data, using, the, seasonal, breeding, adult, 'Djungarian', hamster, '(', 'Phodopus', 'sungorus)', model, challenged, this, assertion, by, demonstrating, a]), verbo([decrease]), complemento([in, 'Sertoli', cell, number, after, gonadotropin, depletion, and, a, return, to, control, levels, following, 7, days, of, 'FSH', replacement])]). relacion([sujeto(['Adult', 'long-day', '(', 'LD)', photoperiod, '(', 16, 'L:8D)', hamsters, were, exposed, to, 'short-day', '(', 'SD)', photoperiod, '(', 8, 'L:16D)', for, 11, wk, to]), verbo([suppress]), complemento([gonadotropins, and, then, received, exogenous, 'FSH', for, up, to, 10, days])]). relacion([sujeto(['Sertoli', cell, proliferation, was, assessed, by, immunofluorescence, by, the, colocalization, of, 'GATA4', and, proliferating, cell]), verbo([nuclear]), complemento([antigen, and, quantified, by, stereology])]). relacion([sujeto(['The', indispensable, 'zinc-finger', transcription, 'factor,', 'Gata1,', is]), verbo([phosphorylated]), complemento([constitutively, at, 6, serine, residues, '(', 26, ',', 49, ',', 72, ',', 142, ',', 178, ',', 187, ')', ',', and, at, a, seventh, '(', 310, ')', following, induction, of, erythroid, differentiation])]). relacion([sujeto(['To', address, this, 'issue,', we, generated, mice, with, 'serine-to-alanine', mutations, at, the, inducibly]), verbo([phosphorylated]), complemento([serine, 310, alone, or, at, conserved, serine, residues, 72, ',', 142, ',', and, 310, together])]). relacion([sujeto(['Analysis', of, hematopoietic, progenitor, populations, during, ontogeny, and, into, adulthood, showed, a, moderate]), verbo([decrease]), complemento([in, erythroid, 'burst-forming', unit, '(', 'BFU-E)', and, erythroid, 'colony-forming', unit, '(', 'CFU-E)', numbers, only, in, the, adult, bone, marrow, of, the, triple, mutant])]). relacion([sujeto(['This']), verbo([suggests]), complemento([that, any, molecular, consequences, associated, with, loss, of, phosphorylation, at, residues, 72, ',', 142, ',', and, 310, can, be, compensated, for, in, the, in, vivo, environment])]). relacion([sujeto(['The', possibility, that, this, mode, might, underlie, 'Down', 'syndrome-related', leukemias]), verbo([caused]), complemento([by, trisomy, of, chromosome, 21, is, discussed])]). relacion([sujeto(['The', chromosomal, translocation, 't(8;21),', generating, the, 'AML1-ETO', fusion, 'protein,', is, frequently]), verbo([associated]), complemento([with, 'French-American-British', '(', 'FAB)', type, 'M2', acute, myeloid, leukemia, '(', 'AML)'])]). relacion([sujeto(['AML1-ETO']), verbo([inhibits]), complemento([normal, definitive, hematopoiesis, and, blocks, erythroid, differentiation])]). relacion([sujeto(['Several', mechanistic, models, for, the, role, of, 'AML1-ETO', in, leukemia, development]), verbo([have]), complemento([emerged, over, the, last, decade])]). relacion([sujeto(['Most', of, these, models]), verbo([have]), complemento([emphasized, the, capacity, of, the, fusion, protein, to, redirect, repressive, 'cofactors,', such, as, histone, deacetylases, '(', 'HDACs)', and, 'DNA', methyltransferases, '(', 'DNMTs),', to, 'RUNX', target, 'genes,', thereby, reversing, the, hematopoietic, transcriptional, program, activated, by, 'wild-type', 'RUNX1a', phenomenon, referred, to, collectively, in, this, review, as, the, &, 'quot;classical"', corepressor, model])]). relacion([sujeto(['Taking', a, candidate, gene, 'approach,', we]), verbo([found]), complemento([no, statistically, significant, differences, between, the, mild, and, severe, patients, groups, in, allelic, or, genotypic, frequencies, for, single, nucleotide, polymorphisms, within, five, genes, known, to, influence, globin, gene, expression, and, erythropoiesis])]). relacion([sujeto(['Alpha', 'hemoglobin-stabilizing', protein, '(', 'AHSP)', is, an, abundant, erythroid, protein, that, specifically]), verbo([binds]), complemento([free, 'alphaHb,', stabilizes, its, 'structure,', and, limits, its, ability, to, participate, in, chemical, reactions, that, generate, reactive, oxygen, species])]). relacion([sujeto(['Gene', ablation, studies, in, mice, demonstrate, that, 'AHSP', is]), verbo([required]), complemento([for, normal, erythropoiesis])]). relacion([sujeto(['AHSP']), verbo([binds]), complemento([the, 'G', and, 'H', helices, of, alphaHb, on, a, surface, that, largely, overlaps, with, the, 'alpha1-beta1', interface, of, 'HbA'])]). relacion([sujeto(['Remarkably,']), verbo([binding]), complemento([of, 'AHSP', to, oxygenated, alphaHb, induces, dramatic, conformational, changes, and, converts, the, 'heme-bound', iron, to, an, oxidized, hemichrome, state, in, which, all, six, coordinate, positions, are, occupied])]). relacion([sujeto(['This', structure, limits, the, reactivity, of, heme, 'iron,']), verbo([providing]), complemento([a, mechanism, by, which, 'AHSP', stabilizes, alphaHb])]). relacion([sujeto(['These', findings]), verbo([suggest]), complemento([a, biochemical, pathway, through, which, 'AHSP', might, participate, in, normal, 'Hb', synthesis, and, modulate, the, severity, of, thalassemias])]). relacion([sujeto(['Moreover,', understanding, how, 'AHSP', stabilizes, alphaHb]), verbo([provides]), complemento([a, theoretical, basis, for, new, strategies, to, inhibit, the, damaging, effects, of, free, alphaHb, that, accumulates, in, 'beta-thalassemia'])]). relacion([sujeto(['We']), verbo([have]), complemento([described, the, application, of, a, simple, biotinylation, tagging, approach, for, the, direct, purification, of, tagged, transcription, factor, 'complexes,', based, on, the, use, of, artificial, short, peptide, tags, that, are, specifically, and, efficiently, biotinylated, by, the, bacterial, 'BirA', biotin, 'ligase,', which, is, 'co-expressed', in, cells, with, the, tagged, factor])]). relacion([sujeto(['We', also]), verbo([provide]), complemento([evidence, that, distinct, 'GATA-1', complexes, are, associated, with, specific, 'GATA-1', functions, in, erythroid, 'differentiation,', for, 'example,', 'GATA-1/Gfi-1b', with, the, suppression, of, cell, proliferation, and, 'GATA-1/FOG-1/MeCP1', with, the, repression, of, other, hematopoietic, transcription, programs])]). relacion([sujeto(['Last,', we, are, in, the, process, of, applying, the, same, technology, to, characterize, the, factors, that, are]), verbo([bound]), complemento([to, the, suppressed, 'gamma-globin', promoter, in, vivo])]). relacion([sujeto(['No', single, gene, responsible, for, the, commitment, of, mesenchymal, cells, to, the, angioblast, cell, fate]), verbo([has]), complemento([been, identified, as, yet])]). relacion([sujeto(['Here', we]), verbo([report]), complemento([characterization, and, functional, studies, of, 'Etsrp,', a, novel, zebrafish, 'ETS', domain, protein])]). relacion([sujeto(['Overexpression', of, etsrp, 'RNA']), verbo([caused]), complemento([multiple, cell, types, to, express, vascular, endothelial, markers])]). relacion([sujeto([etsrp, gene, function, was, also]), verbo([required]), complemento([for, endothelial, marker, induction, by, the, vascular, endothelial, growth, factor, '(', 'vegf)', and, stem, cell, leukemia, '(', 'scl/tal1)'])]). relacion([sujeto(['Ets-1', is, a, widely]), verbo([expressed]), complemento([transcription, factor, implicated, in, 'development,', tumorigenesis, and, hematopoiesis])]). relacion([sujeto(['During', erythroid, 'maturation,', 'Ets-1', is, downmodulated, and, exported, from, the, nucleus, into, the, cytoplasm, through, an, active, mechanism]), verbo([mediated]), complemento([by, a, 'leucine-rich', nuclear, export, signal])]). relacion([sujeto(['In', 'contrast,', during, megakaryocytopoiesis, 'Ets-1']), verbo([increases]), complemento([and, remains, localized, in, the, nucleus, up, to, terminal, maturation])]). relacion([sujeto(['Overexpression', of, 'Ets-1', in, erythroid, cells, blocks, maturation, at, the, polychromatophilic, 'stage,']), verbo([increases]), complemento(['GATA-2', and, decreases, both, 'GATA-1', and, erythropoietin, receptor, expression])]). relacion([sujeto(['Conversely,', 'Ets-1', overexpressing, megakaryocytes, are, characterized, by]), verbo([enhanced]), complemento([differentiation, and, 'maturation,', coupled, with, upmodulation, of, 'GATA-2', and, 'megakaryocyte-specific', genes])]). relacion([sujeto(['We', show, that, 'Ets-1']), verbo([binds]), complemento([to, and, activates, the, 'GATA-2', 'promoter,', in, vitro, and, in, 'vivo,', indicating, that, one, of, the, pathways, through, which, 'Ets-1', blocks, erythroid, and, promotes, 'MK', differentiation, is, via, upmodulation, of, 'GATA-2', expression])]). relacion([sujeto(['Cis', elements, that]), verbo([mediate]), complemento([transcription, factor, binding, are, abundant, within, 'genomes,', but, the, rules, governing, occupancy, of, such, motifs, in, chromatin, are, not, understood])]). relacion([sujeto(['The', transcription, factor, 'GATA-1', that]), verbo([regulates]), complemento([red, blood, cell, development, binds, with, high, affinity, to, 'GATA', 'motifs,', and, initial, studies, suggest, that, these, motifs, are, often, unavailable, for, occupancy, in, chromatin])]). relacion([sujeto(['Whereas', 'GATA-2']), verbo([regulates]), complemento([the, differentiation, of, all, blood, cell, lineages, via, 'GATA', motif, 'binding,', the, specificity, of, 'GATA-2', chromatin, occupancy, has, not, been, studied])]). relacion([sujeto(['We']), verbo([found]), complemento([that, conditionally, active, 'GATA-1', '(', 'ER-GATA-1)', and, 'GATA-2', occupy, only, a, small, subset, of, the, conserved, 'GATA', motifs, within, the, murine, 'beta-globin', locus])]). relacion([sujeto(['Subsequently,', 'ER-GATA-1']), verbo([increased]), complemento([promoter, accessibility, and, occupied, the, betamajor, promoter])]). relacion([sujeto(['ER-GATA-1']), verbo([increased]), complemento([erythroid, 'Krüppel-like', factor, and, 'SWI/SNF', chromatin, remodeling, complex, occupancy, at, restricted, 'LCR', sites])]). relacion([sujeto(['This', cytokine, was, shown, to, contribute, to, inhibition, of, erythroid, maturation, mechanisms, which, are, characterized, by, the, expression, of, specific, genes]), verbo([regulated]), complemento([by, 'GATA-1', and, 'NF-E2', transcription, factors])]). relacion([sujeto(['Here,', we, assessed, the]), verbo([inhibiting]), complemento([effect, of, 'TNFalpha', on, erythroid, differentiation, using, 'K562', cells, which, can, be, chemically, induced, to, differentiate, towards, the, erythroid, pathway, by, aclacinomycin, 'A,', an, anthracyclin])]). relacion([sujeto(['Results', show, that]), verbo([induced]), complemento([hemoglobinization, of, 'K562', cells, as, well, as, 'gamma-globin', and, erythropoietin, receptor, gene, expression, are, decreased, by, 'TNFalpha', via, the, inhibition, of, 'GATA-1', at, its, mRNA, and, protein, expression, level])]). relacion([sujeto(['Additionally,', both, constitutive, and]), verbo([induced]), complemento([binding, activity, of, 'GATA-1', is, abolished, and, induced, activation, of, a, 'GATA-1', driven, luciferase, reporter, construct, is, inhibited])]). relacion([sujeto(['Altogether,', our, results]), verbo([provide]), complemento([insight, into, the, molecular, mechanisms, of, 'inflammation-induced', inhibition, of, erythroid, differentiation])]). relacion([sujeto(['The', pattern, of, the, external, sensory, organs, '(', 'SO)', in, 'Drosophila', depends, on, the, activity, of, the, basic, 'helix-loop-helix', '(', 'bHLH)', transcriptional, activators, 'Achaete/Scute', '(', 'Ac/Sc)', that, are]), verbo([expressed]), complemento([in, clusters, of, cells, '(', 'pro-neural', 'clusters)', and, provide, the, cells, with, the, potential, to, develop, a, neural, fate])]). relacion([sujeto(['In', the, 'mesothorax,', the, 'GATA1', transcription, factor, 'Pannier', '(', 'Pnr),', together, with, its, cofactor, 'Chip,']), verbo([activates]), complemento(['ac/sc', genes, directly, through, binding, to, the, 'dorso-central', enhancer, '(', 'DC)', of, 'ac/sc'])]). relacion([sujeto(['Overexpression', of, 'Isl']), verbo([decreases]), complemento(['pro-neural', expression, and, suppresses, bristle, development])]). relacion([sujeto(['Children', with, 'Down', syndrome, '(', 'DS)', with, acute, megakaryocytic, leukemia, '(', 'AMkL)']), verbo([have]), complemento([very, high, survival, rates, compared, with, 'non-DS', 'AMkL', patients])]). relacion([sujeto(['Somatic', mutations, identified, in, the, 'X-linked', transcription, factor, 'gene,', 'GATA1,', in, essentially, all, 'DS', 'AMkL', cases, result, in, the, synthesis, of, a, shorter, '(', 40, 'kDa)', protein, '(', 'GATA1s)', with, altered, transactivation, activity, and, may]), verbo([lead]), complemento([to, altered, expression, of, 'GATA1', target, genes])]). relacion([sujeto(['Using', the, 'Affymetrix', 'U133A', microarray, 'chip,', we, identified, 551, differentially]), verbo([expressed]), complemento([genes, between, 'DS', and, 'non-DS', 'AMkL', samples])]). relacion([sujeto(['Transcripts', for, the, bone, marrow, 'stromal-cell', antigen, 2, '(', 'BST2)', 'gene,', encoding, a, transmembrane, glycoprotein, potentially]), verbo([involved]), complemento([in, interactions, between, leukemia, cells, and, bone, marrow, stromal, 'cells,', were, 7.3, -, fold, higher, '(', validated, by, 'real-time', polymerase, chain, 'reaction)', in, the, 'non-DS', compared, with, the, 'DS', group])]). relacion([sujeto(['Additional', studies, confirmed, 'GATA1', protein]), verbo([binding]), complemento([and, transactivation, of, the, 'BST2', 'promoter;', 'however,', stimulation, of, 'BST2', promoter, activity, by, 'GATA1s', was, substantially, reduced, compared, with, the, 'full-length', 'GATA1'])]). relacion([sujeto(['Transient', myeloproliferative, disorder, '(', 'TMD)', is]), verbo([found]), complemento([in, 10, '%', of, newborns, with, 'Down', syndrome, '(', 'DS)'])]). relacion([sujeto(['Krüppel-like', factor, 6, '(', 'KLF6)', is, a, member, of, a, growing, family, of, transcription, factors, that, share, a, common, 3, 'C2H2', zinc, finger, 'DNA']), verbo([binding]), complemento([domain, and, have, broad, activity, in, regulating, proliferation, and, development])]). relacion([sujeto(['We']), verbo([have]), complemento([previously, established, that, 'Klf6', is, expressed, in, neuronal, 'tissue,', 'hindgut,', 'heart,', 'lung,', 'kidney,', and, limb, buds, during, midgestation])]). relacion([sujeto(['To', explore, the, potential, role, of, 'Klf6', in, mouse, 'development,', we, analyzed, 'Klf6-/-', mice, and]), verbo([found]), complemento([that, the, homozygous, mutation, is, embryonic, lethal, by, embryonic, day, '(', 'E)', 12.5, and, associated, with, markedly, reduced, hematopoiesis, and, poorly, organized, yolk, sac, vascularization])]). relacion([sujeto(['Prolongation', of, 'epiblast-like', cells, and, delays, in, mesoderm, induction, were, also, observed, in, the, 'Klf6-/-', 'EBs,']), verbo([associated]), complemento([with, delayed, expression, of, 'Brachyury,', 'Klf1,', and, 'Gata1'])]). relacion([sujeto(['Forced', expression, of, 'KLF6', using, a, 'tet-inducible', system]), verbo([enhanced]), complemento([the, hematopoietic, potential, of, 'wild-type', 'EBs'])]). relacion([sujeto(['The', human, reduced, folate, carrier, '(', 'hRFC)', gene]), verbo([has]), complemento([a, complex, regulation, involving, 6, alternatively, spliced, 'non-coding', exons, and, promoters, '(', 'A1/A2,', 'A,', 'B,', 'C,', 'D,', and, 'E)'])]). relacion([sujeto(['The', 'hRFC-A1/A2', promoter, is, unique, in, that, it]), verbo([transcribes]), complemento([a, novel, transcript, with, an, 'in-frame', 'AUG', in, 'non-coding', exon, 'A1/A2', that, encodes, a, modified, hRFC, protein, with, altered, transport, function])]). relacion([sujeto(['Gel', shift, assays, identified, transcription, factor]), verbo([binding]), complemento([to, three, 'E-box', elements, and, one, 'GATA', site, within, this, region])]). relacion([sujeto(['By', real, time, 'PCR', analysis, of, transfected, 'HepG2', 'cells,', 'USF1', and, 'GATA1']), verbo([increased]), complemento([endogenous, 'hRFC-A1/A2', transcripts])]). relacion([sujeto(['Our', results, further, establish, the, complexity, of, hRFC, 'regulation,', as, a, means, of]), verbo([ensuring]), complemento([adequate, folate, cofactor, transport, for, cell, proliferation])]). relacion([sujeto(['We']), verbo([have]), complemento([established, an, innovative, culture, system, for, the, efficient, differentiation, of, hematopoietic, and, endothelial, cells, from, primate, embryonic, stem, '(', 'ES)', cells, without, feeder, 'cells,', embryoid, 'bodies,', or, 'cell-sorting', processes])]). relacion([sujeto(['These', hematopoietic, cells, showed, the, morphology, of, immature, hematopoietic, 'cells,', formed, blast, cell, colonies, with, high, 'efficiency,', and, were, positive, for, 'CD34', 'antigen,', 'KDR,', 'TAL1,', and, 'GATA']), verbo([binding]), complemento([protein, 1, ',', suggesting, that, these, blast, cells, are, equivalent, to, the, multipotent, hematopoietic, progenitor, cells])]). relacion([sujeto(['The', 'finger-like', 'cells,', putative, mesodermal, progenitors, 'and/or', 'hemangioblasts,', actively, proliferated, and, repetitively, produced, hematopoietic, cells, as, long, as, they, were]), verbo([maintained]), complemento([on, the, original, dish])]). relacion([sujeto(['Our', method]), verbo([provides]), complemento([a, highly, controllable, culture, protocol, for, repetitive, production, of, hematopoietic, and, endothelial, cells, from, 'feeder-free', monolayer, cultivation, of, primate, 'ES', cells])]). relacion([sujeto(['VWF,', 'GATA1', and, 'RUNX1', were, strongly]), verbo([expressed]), complemento([in, megakaryocytes, in, both, normal, spleen, and, 'MKL', as, analyzed, by, immunohistochemistry, '(', 'IHC)'])]). relacion([sujeto(['This', is, the, first]), verbo([report]), complemento([of, spontaneous, 'MKL', in, 'mice,', defining, 'VWF', as, a, biomarker, for, diagnosis, and, suggesting, possible, involvement, of, a, series, of, genes, in, disease, pathogenesis])]). relacion([sujeto(['Ablation', of, 'Scl', resulted, in, the]), verbo([loss]), complemento([of, primitive, and, definitive, 'hematopoiesis,', consistent, with, its, essential, role, in, these, processes])]). relacion([sujeto(['Interestingly,', in, embryos, with, severely, reduced, 'Scl', 'levels,', erythroid, progenitors]), verbo([expressing]), complemento([gata1, and, embryonic, globin, developed])]). relacion([sujeto(['Erythroid', maturation, was, deficient, in, these, 'Scl', 'hypomorphs,', supporting, that, 'Scl', was]), verbo([required]), complemento([both, for, the, erythroid, specification, and, for, the, maturation, 'steps,', with, maturation, requiring, higher, 'Scl', levels, than, specification])]). relacion([sujeto(['Although', all, hematopoietic, functions, were, rescued, by, 'wild-type', 'Scl', 'mRNA,', an, 'Scl', 'DNA']), verbo([binding]), complemento([mutant, rescued, primitive, and, definitive, hematopoiesis, but, did, not, rescue, primitive, erythroid, maturation])]). relacion([sujeto(['Together,', we, showed, that, there, is, a, distinct, 'Scl', hypomorphic, phenotype, and, demonstrated, that, distinct, functions, are]), verbo([required]), complemento([for, the, roles, of, 'Scl', in, the, specification, and, differentiation, of, primitive, and, definitive, hematopoietic, lineages])]). relacion([sujeto(['Our', results, revealed, that, 'Scl']), verbo([participates]), complemento([in, multiple, processes, requiring, different, levels, and, functions])]). relacion([sujeto(['Epo-receptor', '(', 'EpoR)', signaling, and, 'GATA-1']), verbo([regulate]), complemento(['proliferation,', 'survival,', 'differentiation,', and, maturation, of, erythroid, cells])]). relacion([sujeto(['Whether', any, signal, that, is, generated, by, 'EpoR']), verbo([targets]), complemento(['GATA-1', or, affects, 'GATA-1', transcriptional, activity, is, not, known])]). relacion([sujeto(['AKT', serine, threonine, kinase]), verbo([phosphorylates]), complemento(['GATA-1S310', in, vitro, and, in, erythroid, cells, and, enhances, 'GATA-1', transcriptional, activity])]). relacion([sujeto(['These', data, demonstrate, that, 'EpoR', signaling]), verbo([phosphorylates]), complemento(['GATA-1', and, modulates, its, activity, via, the, 'PI3-kinase/AKT', signaling, pathway])]). relacion([sujeto(['The', primary, genetic, 'lesion(s),', as, well, as, the, biological, processes, responsible, for, the, typical, structural, changes, of, the, bone, marrow, microenvironment, in, idiopathic, 'myelofibrosis,', are, still, poorly, 'understood,', although, a, central, role, in, disease, pathogenesis]), verbo([has]), complemento([been, attributed, to, the, clonal, proliferation, and, defective, maturation, of, megakaryocytes])]). relacion([sujeto(['Two', animal, models, of, the, disease]), verbo([have]), complemento([been, 'described,', that, in, the, last, few, years, significantly, contributed, to, the, elucidation, of, some, of, the, pathogenetic, steps, of, the, human, 'disease;', these, are, represented, by, mice, genetically, modified, to, overexpress, thrombopoietin, and, by, 'knock-down', mice, with, defective, 'GATA-1', expression, in, megakaryocytes, '(', 'GATA-1(low)', 'mice)'])]). relacion([sujeto(['This', review, will, outline, these, murine, 'models,', both, characterized, by, extensive, accumulation, of, megakaryocytes, in, hematopoietic, 'tissues,', and, illustrate, how, they]), verbo([provided]), complemento([insights, into, the, identification, of, some, of, the, molecules, and, mechanisms, responsible, for, the, development, of, fibrosis, and, osteosclerosis, that, present, major, similarities, with, those, observed, in, patients, with, idiopathic, myelofibrosis])]). relacion([sujeto(['The', remarkable, high, affinity, '(', 'Kd', approximately, 10, '(', -, 15, ')', 'M)', of, 'avidin/streptavidin', for, biotin]), verbo([has]), complemento([been, extensively, exploited, in, purification, methodologies])]). relacion([sujeto(['Recently', a, small, peptide, sequence, '(', 'Avi-tag)']), verbo([has]), complemento([been, defined, that, can, be, specifically, and, efficiently, biotinylated, by, the, bacterial, 'BirA', biotin, ligase])]). relacion([sujeto(['Fusion', of, this, small, peptide, sequence, to, a, protein, of, interest, and, 'co-expression', with, the, 'BirA', gene, in, mammalian, cells, allowed, purification, of, the, biotinylated, protein, together, with, its]), verbo([associated]), complemento([proteins, and, other, molecules])]). relacion([sujeto(['To', make, this, approach, feasible, for, a, large, variety, of, proteins, we, developed, a, mouse, strain, that]), verbo([expresses]), complemento([the, 'BirA', gene, ubiquitously, by, inserting, it, in, the, 'ROSA26', locus])]). relacion([sujeto(['We', demonstrate, that, the, 'BirA', protein, is, indeed]), verbo([expressed]), complemento([in, all, tissues, tested])]). relacion([sujeto(['To', observe, the, 'differentiation-inducing', properties, of, the, novel, erythroid, differentiation, related, gene, 'EDRF1,', and, demonstrate, its, functioning, pathway]), verbo([involved]), complemento([in, regulation, of, 'alpha-', and, 'gamma-globin', gene, expression])]). relacion([sujeto(['In', antisense, 'EDRF1', overexpressed, 'HEL', 'cells,', significant]), verbo([loss]), complemento([of, 'alpha-', and, 'gamma-globin', mRNA, synthesis, was, observed])]). relacion([sujeto(['No', significant, change, was]), verbo([found]), complemento([in, expression, of, transcription, factors, 'GATA-1', and, 'NF-E2', in, 'HEL', cells, transfected, with, empty, 'carrier,', sense, expression, 'carrier,', and, antisense, expression, carrier])]). relacion([sujeto(['EDRF1']), verbo([regulates]), complemento(['alpha-', and, 'gamma-globin', gene, synthesis, by, modulating, 'DNA-binding', activity, of, 'GATA-1', transcription, factor])]). relacion([sujeto(['Overexpression', and, underexpression, of, 'EDRF1', do, not, significantly]), verbo([regulate]), complemento([the, expression, of, 'GATA-1', and, 'NF-E2', mRNA])]). relacion([sujeto(['Alpha-hemoglobin-stabilizing', protein, '(', 'AHSP)', is, an, erythroid, protein, that]), verbo([binds]), complemento([and, stabilizes, 'alpha-hemoglobin', during, normal, erythropoiesis, and, in, pathological, states, of, 'alpha-hemoglobin', excess])]). relacion([sujeto(['AHSP']), verbo([has]), complemento([been, proposed, as, a, candidate, gene, in, some, 'Heinz', body, hemolytic, anemias, and, as, a, modifier, gene, in, the, 'beta-thalassemia', syndromes])]). relacion([sujeto(['To']), verbo([gain]), complemento([additional, insight, into, the, molecular, mechanisms, controlling, the, 'erythroid-specific', expression, of, the, 'AHSP', gene, and, provide, the, necessary, tools, for, further, genetic, studies, of, these, 'disorders,', we, have, initiated, identification, and, characterization, of, the, regulatory, elements, controlling, the, human, 'AHSP', gene])]). relacion([sujeto(['In', vitro, studies, using, transfection, of, 'promoter/reporter', plasmids, in, human, tissue, culture, cell, 'lines,', 'DNase', 'I', footprinting, analyses, and, gel, mobility, shift, 'assays,', identified, an, 'AHSP', gene, erythroid, promoter, with, functionally, important]), verbo([binding]), complemento([sites, for, 'GATA-1-', and, 'Oct-1-related', proteins])]). relacion([sujeto(['In', transgenic, 'mice,', a, reporter, gene, directed, by, a, minimal, human, 'AHSP', promoter, was]), verbo([expressed]), complemento([in, bone, 'marrow,', 'spleen,', and, 'reticulocytes,', but, not, in, nonerythroid, tissues])]). relacion([sujeto(['The', 'AHSP', promoter, is, an, excellent, candidate, region, for, mutations]), verbo([associated]), complemento([with, decreased, 'AHSP', gene, expression])]). relacion([sujeto(['We']), verbo([have]), complemento([previously, described, the, characterization, of, a, 265, bp, insulator, 'element,', termed, 'sns,', localized, at, the, 3, '\'', end, of, the, early, histone, 'H2A', gene, of, the, sea, urchin, 'Paracentrotus', lividus])]). relacion([sujeto(['This', sequence, contains, three, 'cis-acting', elements, '(', 'Box', 'A,', 'Box', 'B,', and, 'Box', 'C', +, 'T)', all, needed, for, the, 'enhancer-blocking', activity, in, both]), verbo([sea]), complemento([urchin, and, human, cells])]). relacion([sujeto(['The', goal, of, this, study, was, to, further, characterize, the]), verbo([sea]), complemento([urchin, sns, insulator, in, the, erythroid, environment])]). relacion([sujeto(['We']), verbo([found]), complemento([that, the, sns, sequence, displays, directional, 'enhancer-blocking', activity])]). relacion([sujeto(['By', the, use, of, antibodies, against, known, 'DNA']), verbo([binding]), complemento(['proteins,', in, electrophoretic, mobility, shift, 'assays,', we, demonstrated, the, binding, of, the, 'erythroid-specific', 'GATA-1', and, the, ubiquitous, 'Oct-1', and, 'Sp1', transcription, factors])]). relacion([sujeto(['These', factors]), verbo([bind]), complemento([to, 'Box', 'A,', 'Box', 'B,', and, 'Box', 'C', +, 'T,', 'respectively,', in, both, 'K562', and, 'MEL', nuclear, extracts])]). relacion([sujeto(['These', results, may]), verbo([have]), complemento([significant, implications, for, the, conservation, of, insulator, function, in, evolutionary, distant, organisms, and, may, prove, to, be, of, practical, benefit, in, gene, transfer, applications, for, erythroid, disorders, such, as, hemoglobinopathies, and, thalassemias])]). relacion([sujeto(['Our', laboratory]), verbo([has]), complemento([previously, defined, the, human, 'Gfi-1B', promoter, region, and, shown, that, 'GATA-1', mediates, 'erythroid-specific', 'Gfi-1B', transcription])]). relacion([sujeto(['By', further, investigating, the, regulation, of, the, 'Gfi-1B', 'promoter,', here, we]), verbo([report]), complemento([that, '(', 'i)', 'Gfi-1B', transcription, is, negatively, regulated, by, its, own, gene, 'product,', '(', 'ii)', 'GATA-1,', instead, of, 'Gfi-1B,', binds, directly, to, the, 'Gfi-1-like', sites, in, the, 'Gfi-1B', promoter, and, '(', 'iii)', 'Gfi-1B', suppresses, 'GATA-1-mediated', stimulation, of, 'Gfi-1B', promoter, through, their, protein, interaction])]). relacion([sujeto(['These', results, not, only, demonstrate, that, interaction, of, 'GATA-1', and, 'Gfi-1B']), verbo([participates]), complemento([in, a, feedback, regulatory, pathway, in, controlling, the, expression, of, the, 'Gfi-1B', 'gene,', but, also, provide, the, first, evidence, that, 'Gfi-1B', can, exert, its, repression, function, by, acting, on, 'GATA-1-mediated', transcription, without, direct, binding, to, the, 'Gfi-1', site, of, the, target, genes])]). relacion([sujeto(['To', define, the, roles, of, 'GATA-1', in, the, production, and, differentiation, of, primitive, and, definitive, 'erythrocytes,', we, established, 'GATA-1-null', embryonic, stem, cell, lines, in, which, 'GATA-1', was, able, to, be, conditionally]), verbo([expressed]), complemento([by, using, the, tetracycline, conditional, gene, expression, system])]). relacion([sujeto(['We']), verbo([expressed]), complemento(['GATA-1', in, the, course, of, primitive, and, definitive, erythropoiesis, and, analyzed, the, ability, of, 'GATA-1', to, rescue, the, defective, erythropoiesis, caused, by, the, 'GATA-1', null, mutation])]). relacion([sujeto(['The', 'early-stage', expression, of, 'GATA-1', during, both, primitive, and, definitive, erythropoiesis, was, sufficient, to]), verbo([promote]), complemento([the, proliferation, of, red, blood, cells])]). relacion([sujeto(['The', 'DNA-binding', hemopoietic, zinc, finger, transcription, factor, 'GATA1']), verbo([promotes]), complemento([terminal, megakaryocyte, differentiation, and, restrains, abnormal, immature, megakaryocyte, expansion])]). relacion([sujeto(['Previous', studies, of, synthetic, and, naturally, occurring, mutant, 'GATA1', molecules, demonstrate, that, 'DNA-binding', and, interaction, with, the, essential, 'GATA1', cofactor, 'FOG-1', '(', via, the, 'N-terminal', 'finger)', are]), verbo([required]), complemento([for, gene, expression, in, terminally, differentiating, megakaryocytes, and, for, platelet, production])]). relacion([sujeto(['In', this, 'study,', we]), verbo([have]), complemento([systematically, dissected, 'GATA1', domains, required, for, platelet, release, and, control, of, megakaryocyte, growth, by, ectopically, expressing, modified, 'GATA1', molecules, in, primary, 'GATA1-deficient', fetal, megakaryocyte, progenitors])]). relacion([sujeto(['In', addition, to, 'DNA', 'binding,', distinct, 'N-terminal', 'regions,', including, residues, in, the, first, 84, amino, 'acids,']), verbo([promote]), complemento([platelet, release, and, restrict, megakaryocyte, growth])]). relacion([sujeto(['In', 'contrast,', abrogation, of, 'GATA1-FOG-1', interaction]), verbo([leads]), complemento([to, loss, of, 'differentiation,', but, growth, of, blocked, immature, megakaryocytes, is, controlled])]). relacion([sujeto(['Thus,', distinct, 'GATA1', domains]), verbo([regulate]), complemento([terminal, megakaryocyte, gene, expression, leading, to, platelet, release, and, restrain, megakaryocyte, 'growth,', and, these, processes, can, be, uncoupled])]). relacion([sujeto(['GATA-1,', one, of, the, hematopoietically]), verbo([expressed]), complemento(['members,', is, required, for, normal, erythroid, and, megakaryocytic, differentiation])]). relacion([sujeto(['Over', the, past, few, 'years,', mutations, in, the, gene, encoding, 'GATA-1']), verbo([have]), complemento([been, linked, to, several, human, hematologic, 'disorders,', including, 'X-linked', dyserythropoietic, anemia, and, 'thrombocytopenia,', 'X-linked', thrombocytopenia, and, 'beta-thalassemia,', and, 'Down', syndrome, acute, megakaryoblastic, leukemia])]). relacion([sujeto(['Here,', we]), verbo([have]), complemento([studied, how, transcription, of, alpha, globin, is, placed, in, the, broader, context, of, apoptosis])]). relacion([sujeto(['GATA-1', was]), verbo([expressed]), complemento([at, low, levels, and, was, weakly, induced, while, 'GATA-3', was, completely, absent])]). relacion([sujeto(['Transduction', of, antisense, 'GATA-2']), verbo([prevented]), complemento([both, increase, of, 'GATA-2', and, alpha, globin, under, apoptotic, conditions, and, delayed, cell, death])]). relacion([sujeto(['We']), verbo([suggest]), complemento([a, role, of, 'GATA-2', in, apoptosis, besides, its, function, in, maintenance, and, proliferation, of, immature, hematopoietic, progenitors])]). relacion([sujeto(['Two', murine, bipotent, 'erythroid/megakaryocytic', 'cells,', the, progenitor, '(', 'MEP)', and, precursor, '(', 'PEM)', 'cells,', recently]), verbo([have]), complemento([been, identified, on, the, basis, of, the, phenotypes, of, 'linnegc-kitposSca-1neg', 'CD16/CD32lowCD34low', and, 'TER119pos4A5pos', or, 2, 'D5pos,', respectively])]). relacion([sujeto(['MEP', 'cells,', but, not, 'PEM', 'cells,']), verbo([express]), complemento(['c-kit,', respond, to, stem, cell, factor, in, 'vitro,', and, form, spleen, colonies, in, vivo])]). relacion([sujeto(['PEM', cells]), verbo([increase]), complemento([10, -, to, 20, -, fold, under, acute, and, chronic, 'stress,', whereas, 'MEP', cell, increases, '(', 21, '%', -, 84, '%', ')', are, observed, only, in, acutely, stressed, animals])]). relacion([sujeto(['These', data]), verbo([suggest]), complemento([that, 'MEP', and, 'PEM', cells, represent, distinct, cell, populations, that, may, exist, in, an, 'upstream-downstream', differentiation, relationship, under, conditions, of, stress])]). relacion([sujeto(['Whereas', the, dynamics, of, both, populations, are, altered, by, stress, 'induction,', the, differential, response, to, acute, and, chronic, stress]), verbo([suggests]), complemento([different, regulatory, mechanisms])]). relacion([sujeto(['Murine', gene]), verbo([targeting]), complemento([and, analysis, of, naturally, occurring, human, mutations, demonstrate, that, 'GATA-1', drives, the, maturation, of, committed, erythroid, precursors, and, megakaryocytes])]). relacion([sujeto(['Prior', studies, also]), verbo([suggest]), complemento(['additional,', poorly, 'defined,', roles, for, 'GATA-1', at, earlier, stages, of, erythromegakaryocytic, differentiation])]). relacion([sujeto(['To', investigate, these, functions, 'further,', we]), verbo([stimulated]), complemento(['Gata1-', murine, embryonic, 'stem-cell-derived', hematopoietic, cultures, with, 'thrombopoietin,', a, multistage, cytokine])]). relacion([sujeto(['However,', these, were, rapidly, overgrown, by, a, unique, population, of, 'thrombopoietin-dependent', blasts, that]), verbo([express]), complemento([immature, markers, and, proliferate, indefinitely])]). relacion([sujeto(['Importantly,', on, restoration, of, 'GATA-1', 'function,', these, cells, differentiated, into, both, erythroid, and, megakaryocytic, 'lineages,']), verbo([suggesting]), complemento([that, they, represent, bipotential, progenitors])]). relacion([sujeto(['Our', findings, indicate, that]), verbo([loss]), complemento([of, 'GATA-1', impairs, the, maturation, of, 'megakaryocyte-erythroid', progenitors])]). relacion([sujeto(['This', defines, a, new, role, for, 'GATA-1', at, a, relatively, early, stage, of, hematopoiesis, and]), verbo([provides]), complemento([potential, insight, into, recent, discoveries, that, human, 'GATA1', mutations, promote, acute, megakaryoblastic, 'leukemia,', a, clonal, malignancy, with, features, of, both, erythroid, and, megakaryocyte, maturation])]). relacion([sujeto(['Platelet', factor, 4, '(', 'PF4)', is]), verbo([expressed]), complemento([exclusively, in, megakaryocytes, and, platelets, and, serves, as, a, 'lineage-specific', marker, of, megakaryocytic, differentiation])]). relacion([sujeto(['Recently,', we]), verbo([have]), complemento([determined, the, novel, regulatory, element, termed, &, 'quot;TME"', in, the, 'PF4', promoter, and, identified, a, group, of, binding, proteins, from, megakaryocytic, 'HEL', cells])]). relacion([sujeto(['Acquired', additions, of, chromosome, 21, are, a, common]), verbo([finding]), complemento([in, 'leukemias,', suggesting, a, contributory, role, to, leukemogenesis])]). relacion([sujeto(['We', and, others]), verbo([have]), complemento([shown, acquired, mutations, in, the, 'X', chromosome, gene, 'GATA1', in, all, these, cases])]). relacion([sujeto(['The', gene, or, genes, on, chromosome, 21, whose, overexpression]), verbo([promote]), complemento([the, megakaryoblastic, phenotype, are, presently, unknown])]). relacion([sujeto(['We', show, that, 'ERG', is]), verbo([expressed]), complemento([in, hematopoietic, stem, 'cells,', megakaryoblastic, cell, 'lines,', and, in, primary, leukemic, cells, from, 'Down', syndrome, patients])]). relacion([sujeto(['ERG', expression, is]), verbo([induced]), complemento([upon, megakaryocytic, differentiation, of, the, erythroleukemia, cell, lines, 'K562', and, 'UT-7,', and, forced, expression, of, 'ERG', in, 'K562', cells, induces, erythroid, to, megakaryoblastic, phenotypic, switch])]). relacion([sujeto(['We', also, show, that, 'ERG']), verbo([activates]), complemento([the, gpIb, megakaryocytic, promoter, and, binds, the, gpIIb, promoter, in, vivo])]). relacion([sujeto(['Furthermore,', both, 'ERG', and, 'ETS2']), verbo([bind]), complemento([in, vivo, the, hematopoietic, enhancer, of, 'SCL/TAL1,', a, key, regulator, of, hematopoietic, stem, cell, and, megakaryocytic, development])]). relacion([sujeto(['We', propose, that, trisomy, 21, facilitates, the, occurrence, of, megakaryoblastic, leukemias, through, a, shift, toward, the, megakaryoblastic, lineage]), verbo([caused]), complemento([by, the, excess, expression, of, 'ERG,', and, possibly, by, other, chromosome, 21, 'genes,', such, as, 'RUNX1', and, 'ETS2,', in, hematopoietic, progenitor, 'cells,', coupled, with, a, differentiation, arrest, caused, by, the, acquisition, of, mutations, in, 'GATA1'])]). relacion([sujeto(['The', abnormal, megakaryocytopoiesis]), verbo([associated]), complemento([with, idiopathic, myelofibrosis, '(', 'IM)', plays, a, role, in, its, pathogenesis])]). relacion([sujeto(['We', conclude, that, megakaryocytes, from, 'IM', patients]), verbo([have]), complemento([reduced, 'GATA-1', 'content,', possibly, contributing, to, disease, pathogenesis, as, in, the, 'GATA-1(low)', mice, and, also, representing, a, novel, 'IM-associated', marker])]). relacion([sujeto(['Selective', expression, of, viral, receptors]), verbo([has]), complemento([the, potential, to, attenuate, infection, of, susceptible, tissues, by, redirecting, virus, to, cells, that, cannot, support, viral, replication])]). relacion([sujeto(['To', test, this, 'hypothesis,', we, generated, a, transgenic, 'mouse,', termed, globin, transcription, factor, 1, '(', 'GATA1)-coxsackie', and, adenovirus, receptor, '(', 'CAR),', that]), verbo([expressed]), complemento([the, 'CAR', on, erythrocytes])]). relacion([sujeto(['Although', all, the, 'Gata1low', mice, developed, fibrosis, at, 12, to, 13, 'months,', variegations, were, observed, in, the, severity, of, the, phenotype]), verbo([expressed]), complemento([by, mutants, of, different, backgrounds])]). relacion([sujeto(['In', 'C57BL/6', 'mice,', the, mutation, was, no, longer, inherited, in, a, 'Mendelian', 'fashion,', and, fibrosis, was]), verbo([associated]), complemento([with, massive, osteosclerosis])]). relacion([sujeto(['Instead,', 'DBA/2', 'mutants,', although, severely, 'anemic,']), verbo([expressed]), complemento([limited, fibrosis, and, osteosclerosis, and, did, not, present, 'tear-drop', poikilocytes, in, blood, or, extramedullary, hemopoiesis, in, liver, up, to, 20, months, of, age])]). relacion([sujeto(['We', propose, that, the, variegation, in, myelofibrosis]), verbo([expressed]), complemento([by, 'Gata1low', mutants, of, different, strains, might, represent, a, model, to, study, the, variability, of, the, clinical, picture, of, the, human, disease])]). relacion([sujeto(['The', contribution, of, erythropoietin, to, the, differentiation, of, the, red, blood, cell, lineage, remains, 'elusive,', and, the, demonstration, of, a, molecular, link, between, erythropoietin, and, the, transcription, of, genes]), verbo([associated]), complemento([with, erythroid, differentiation, is, lacking])]). relacion([sujeto(['We']), verbo([report]), complemento([here, that, erythropoietin, regulates, the, transcription, of, the, 'TIMP-1', gene, upon, binding, to, its, receptor, in, erythroid, cells, by, triggering, the, activation, of, phosphatidylinositol, 3, -, kinase, '(', 'PI3K)/Akt'])]). relacion([sujeto(['We']), verbo([found]), complemento([that, 'Akt', directly, phosphorylates, the, transcription, factor, 'GATA-1', at, serine, 310, and, that, this, 'site-specific', phosphorylation, is, required, for, the, transcriptional, activation, of, the, 'TIMP-1', promoter])]). relacion([sujeto(['Conversely,', 'TIMP-1', secretion, is, profoundly]), verbo([decreased]), complemento([in, erythroid, cells, from, fetal, livers, of, transgenic, 'knock-in', mice, homozygous, for, a, 'GATA(S310A)', 'gene,', which, encodes, a, 'GATA-1', mutant, that, cannot, be, phosphorylated, at, 'Ser(310)'])]). relacion([sujeto(['Furthermore,', 'retrovirus-mediated', expression, of, 'GATA(S310A)', into, 'GATA-1(null)-derived', embryonic, stem, cells]), verbo([decreases]), complemento([the, rate, of, hemoglobinization, by, more, than, 50, '%', compared, to, expressed, 'wild-type', 'GATA-1'])]). relacion([sujeto(['These', findings]), verbo([provide]), complemento([the, first, example, of, a, chain, of, coupling, mechanisms, between, the, binding, of, erythropoietin, to, its, receptor, and, 'GATA-1-dependent', gene, expression])]). relacion([sujeto(['Hematopoiesis', is, a, complex, process]), verbo([regulated]), complemento([by, nuclear, proteins, that, coordinate, 'lineage-specific', patterns, of, gene, expression])]). relacion([sujeto(['Targeted', mutagenesis]), verbo([has]), complemento([revealed, critical, roles, for, the, 'X-linked', transcription, factor, 'GATA-1', in, erythrocyte, and, megakaryocyte, differentiation])]). relacion([sujeto(['GATA-1']), verbo([has]), complemento([two, zinc, fingers, essential, for, normal, function])]). relacion([sujeto(['The', 'N-terminal', finger]), verbo([mediates]), complemento([interaction, with, 'FOG-1,', a, cofactor, for, 'GATA-1'])]). relacion([sujeto(['Here', we]), verbo([report]), complemento([a, family, with, a, novel, single, base, mutation, that, results, in, an, amino, acid, substitution, '(', 'Gly208Arg)', within, the, highly, conserved, portion, of, the, 'GATA-1', 'N-terminal', finger, 'domain,', leading, to, dyserythropoietic, anemia, and, macrothrombocytopenia])]). relacion([sujeto(['Another', mutation, described, at, the, same, codon, '(', 208, ')']), verbo([has]), complemento([been, found, to, be, associated, with, thrombocytopenia, only])]). relacion([sujeto([1, ',', a, hematopoietic, 'Ets', transcription, 'factor,', is]), verbo([required]), complemento([for, development, of, the, lymphoid, and, myeloid, lineages])]). relacion([sujeto(['We']), verbo([have]), complemento([previously, shown, that, 'PU'])]). relacion([sujeto([1, is, responsible, for, switching, its, association, between, 'co-activators', and, 'co-repressors,', we, examined, whether, acetylation]), verbo([regulates]), complemento([the, physical, and, functional, activities, of, 'PU'])]). relacion([sujeto([1]), verbo([induced]), complemento([differentiation, 'block,', growth, 'inhibition,', and, apoptotic, cell, death, in, 'MEL', erythroleukemia, cells, as, we, reported, 'previously,', overexpression, of, the, 'mutant-acetylation', motif, 'PU'])]). relacion([sujeto(['Taken', 'together,', our, data]), verbo([suggest]), complemento([that, acetylation, might, regulate, the, biological, functions, of, 'PU'])]). relacion([sujeto(['GATA-1']), verbo([regulates]), complemento([the, expression, of, many, genes, within, these, lineages, and, its, functionality, depends, upon, its, ability, to, bind, both, 'DNA', and, protein, partners])]). relacion([sujeto(['Disruption', of, either, of, these, functions]), verbo([causes]), complemento([severe, hematopoietic, dysfunction, and, results, in, blood, 'disorders,', such, as, thrombocytopenia, and, anemia])]). relacion([sujeto(['They', depended, on, 'TPO', for, survival, and, proliferation, 'and,', although]), verbo([retaining]), complemento([the, capacity, to, grow, in, 'IL-3,', did, not, respond, to, either, 'EPO,', 'G-CSF', or, 'GM-CSF'])]). relacion([sujeto([32, 'D', 'TPO', cells]), verbo([expressed]), complemento(['Mk-specific', markers, by, 'FACS', '(', 'CD41,', 'CD61', and, 2, 'D5)', and, 'RT-PCR', '(', acetyl, cholinesterase, 'E', and, platelet, factor, 4, ')', and, their, unique, 'profile,', by, gene, array, 'analysis,', included, expression, of, urokinase, plasminogen, activator, surface, receptor, '(', 'CD87', or, 'uPAR),', plasminogen, activator, inhibitor, and, coagulation, factor, 'II', '(', 'thrombin)', receptor, '(', 'Cf2r)'])]). relacion([sujeto(['In', 'addition,', by, quantitative, 'RT-PCR,', 32, 'D', 'TPO', clones]), verbo([expressed]), complemento([levels, of, 'Gata1', similar, to, those, expressed, by, freshly, isolated, 'Mks', '(', 'DeltaCt', approximately, 4.7, in, both, 'cases)'])]). relacion([sujeto(['We', investigated, the, expression, of, proliferative, cell]), verbo([nuclear]), complemento([antigen, '(', 'PCNA)', in, zebrafish, to, delineate, the, proliferative, hematopoietic, component, during, adult, and, embryonic, hematopoiesis])]). relacion([sujeto(['Immunostaining', for, 'PCNA', and]), verbo([enhanced]), complemento([green, fluorescence, protein, '(', 'eGFP)', was, performed, in, 'wild-type', and, 'fli1-eGFP', '(', endothelial, 'marker)', and, 'gata1-eGFP', '(', erythroid, cell, 'marker)', transgenic, fish])]). relacion([sujeto(['PCNA', was]), verbo([expressed]), complemento([in, hematopoietic, progenitor, cells, but, not, in, mature, 'neutrophils,', eosinophils, or, erythroid, cells])]). relacion([sujeto(['Some', 'PCNA+', cells, are, scattered, in, the, hematopoietic, compartment, of, the, kidney, while, others, are, closely]), verbo([associated]), complemento([with, renal, tubular, cells])]). relacion([sujeto(['PCNA', was, also]), verbo([expressed]), complemento([in, spermatogonial, stem, cells, and, intestine, 'crypts,', consistent, with, its, role, in, cell, proliferation, and, 'DNA', synthesis])]). relacion([sujeto(['In', 'embryos,', 'PCNA', is]), verbo([expressed]), complemento([in, the, 'brain,', spinal, cord, and, intermediate, cell, mass, '(', 'ICM)', at, 24, 'h-post', fertilization])]). relacion([sujeto(['Therefore,', 'PCNA', can, be, used, to, mark, cell, proliferation, in, zebrafish, hematopoietic, tissues, and, to, identify, a, population, of, progenitor, cells, whose, significance, would]), verbo([have]), complemento([to, be, further, investigated])]). relacion([sujeto(['We', examined, how, these, proteins]), verbo([interact]), complemento([functionally, in, 'G1E', 'cells,', a, 'GATA-1(-)', erythroblast, line, that, proliferates, in, an, 'SCF-dependent', fashion, 'and,', upon, restoration, of, 'GATA-1', 'function,', undergoes, 'GATA-1', proliferation, arrest, and, 'Epo-dependent', terminal, maturation])]). relacion([sujeto(['We', show, that, 'SCF-induced', cell, cycle, progression, is]), verbo([mediated]), complemento([via, activation, of, the, 'Src', 'kinase/c-Myc', pathway])]). relacion([sujeto(['Restoration', of, 'GATA-1', activity]), verbo([induced]), complemento(['G1', cell, cycle, arrest, coincident, with, repression, of, 'c-Kit', and, its, downstream, effectors, 'Vav1,', 'Rac1,', and, 'Akt'])]). relacion([sujeto(['Sustained', expression, of, each, of, these, individual, signaling, components]), verbo([inhibited]), complemento(['GATA-1-induced', cell, cycle, arrest, to, various, degrees, but, had, no, effects, on, the, expression, of, 'GATA-1-regulated', erythroid, maturation, markers])]). relacion([sujeto(['Chromatin', immunoprecipitation, analysis, revealed, that, 'GATA-1', occupies, a, defined, 'Kit', gene, regulatory, element, in, 'vivo,']), verbo([suggesting]), complemento([a, direct, mechanism, for, gene, repression])]). relacion([sujeto(['Hence,', in, addition, to, its, 'well-established', function, as, an, activator, of, erythroid, 'genes,', 'GATA-1', also]), verbo([participates]), complemento([in, a, distinct, genetic, program, that, inhibits, cell, proliferation, by, repressing, the, expression, of, multiple, components, of, the, 'c-Kit', signaling, axis])]). relacion([sujeto(['Our', findings]), verbo([reveal]), complemento([a, novel, aspect, of, molecular, cross, talk, between, essential, transcriptional, and, cytokine, signaling, components, of, hematopoietic, development])]). relacion([sujeto(['In', the, 'rat,', the, 'alpha2B-adrenergic', receptor, '(', 'alpha2B-AR)', is, encoded, by, the, rat, 'non-glycosylated', '(', 'RNG)', gene, and, is, primarily]), verbo([expressed]), complemento([in, the, 'kidney,', brain, and, liver, of, adult, animals])]). relacion([sujeto(['High', levels, of, 'alpha2B-AR', are, also]), verbo([found]), complemento([during, fetal, life, in, the, 'placenta,', liver, and, 'blood,', where, it, is, borne, by, cells, of, the, erythropoietic, lineage])]). relacion([sujeto(['EMSA', showed, specific]), verbo([binding]), complemento([of, 'GATA1', and, 'NF-E2', to, these, elements])]). relacion([sujeto(['Taken', 'together,', the, results]), verbo([suggest]), complemento([that, the, chromatin, environment, in, the, vicinity, of, these, boxes, plays, a, critical, role, for, 'alpha2B-AR', expression, during, fetal, life])]). relacion([sujeto(['(', 'Rutaceae),']), verbo([has]), complemento([been, tested, on, the, erythroleukemic, cell, line, 'K562', in, order, to, explain, some, previous, results, on, cell, differentiation])]). relacion([sujeto(['In', this, study, we, showed, that, fagaronine]), verbo([induces]), complemento([a, significant, hemoglobinization, of, the, human, erythroleukemic, cell, line, 'K562'])]). relacion([sujeto(['This', hemoglobin, synthesis, was, accompanied, by, a, strong]), verbo([increase]), complemento([of, erythroid, mRNA, expression, such, as, 'gamma-', and, 'alpha-globin,', and, 'PBGD,', an, enzyme, of, heme, synthesis])]). relacion([sujeto(['In', 'addition,', the, 'Epo-R', transcripts, were, also]), verbo([stimulated]), complemento([indicating, that, cells, are, engaged, in, a, maturation, process])]). relacion([sujeto(['Both', transcription, factors, 'GATA-1', and, 'NF-E2,', which, play, an, important, role, in, the, regulation, of, genes]), verbo([involved]), complemento([in, the, erythroid, 'differentiation,', were, also, transcriptionally, 'up-regulated'])]). relacion([sujeto(['To', elucidate, the, possible, role, of, 'GATA-1', in, the, 'FAG-induced', differentiation, of, 'K562', 'cells,', we, transfected, reporter, constructs, containing, regulatory, regions, of, erythroid, genes, encompassing, 'GATA-1']), verbo([binding]), complemento([sites])]). relacion([sujeto(['After', 48, hours, of, 'treatment,', 'FAG']), verbo([stimulated]), complemento([the, 'EPO-R', and, 'gamma-globin', promoters, by, 2, -, to, 3, -, fold, and, the, 'promoter/enhancer', region, of, 'GATA-1', gene, by, 3.2, -, fold])]). relacion([sujeto(['A', mutation, within, the, 'GATA-1']), verbo([binding]), complemento([sites, strongly, decreased, the, promoter, activation, induced, by, 'FAG'])]). relacion([sujeto(['Taken', 'together,', our, results, represent, a, demonstration, that, 'FAG', exerts, its, differentiating, activity, by, a, specific, activation, of, the]), verbo([regulating]), complemento(['GATA-1', regions, of, genes, involved, in, the, erythroid, phenotype, expression])]). relacion([sujeto(['In', the, interleukin, 3, -, dependent, hematopoietic, cell, line, 'Ba/F3,', inhibition, of, 'mitogen-activated', protein, 'kinase,', a, member, of, the, 'MAPK/c-Jun', 'N-terminal', 'kinase/stress-activated', protein, kinase, kinase, family, that, plays, an, important, role, in, cell, growth, and, death, 'control,', rapidly]), verbo([leads]), complemento([to, severe, apoptosis])]). relacion([sujeto(['Here', we]), verbo([report]), complemento(['that,', upon, 'interleukin-3', stimulation, of, 'Ba/F3', 'cells,', the, transcription, factor, 'GATA-1', is, strongly, phosphorylated, at, residue, serine, 26, by, a, 'MAPK-dependent', pathway])]). relacion([sujeto(['Phosphorylation', of, 'GATA-1']), verbo([increases]), complemento(['GATA-1-mediated', transcription, of, the, 'E4bp4', survival, gene, without, significantly, changing, the, 'DNA-binding', affinity, of, 'GATA-1'])]). relacion([sujeto(['Further', characterization, of, 'GATA-1', phosphorylation, site, mutants, revealed, that, the, antiapoptotic, function, of, 'GATA-1', is, strongly, dependent, upon, its, phosphorylation, at, the, 'Ser-26', position, and, is, probably]), verbo([mediated]), complemento([through, its, 'up-regulation', of, 'Bcl-X(L)', expression])]). relacion([sujeto(['The', concentration, of, 'GATA-1', 'is,', in, 'turn,']), verbo([regulated]), complemento([by, specific, sequences, within, the, 'GATA-1', locus])]). relacion([sujeto(['On', the, basis, of, its, levels, of, 'expression,', the, 'GATA-1', protein, becomes]), verbo([associated]), complemento([with, suitable, partners, forming, transcription, complexes, 'that,', by, binding, to, 'lineage-specific', 'enhancers,', activate, the, expression, of, the, corresponding, target, genes])]). relacion([sujeto(['Instrumental', to, our, understanding, of, the, role, of, 'GATA-1', in, hemopoietic, differentiation]), verbo([has]), complemento([been, the, generation, of, genetically, engineered, mutant, mice, and, the, discovery, of, naturally, occurring, mutations, associated, with, either, inherited, or, acquired, human, pathologies])]). relacion([sujeto(['Within', the, 'short-term', culture, of, 'GMPs,', the, eosinophil, potential, was]), verbo([found]), complemento([exclusively, in, cells, activating, the, transgenic, reporter, for, 'GATA-1,', a, transcription, factor, capable, of, instructing, eosinophil, lineage, commitment])]). relacion([sujeto(['EoPs', significantly]), verbo([increased]), complemento([in, number, in, response, to, helminth, 'infection,', suggesting, that, the, 'EoP', stage, is, physiologically, involved, in, eosinophil, production, in, vivo])]). relacion([sujeto(['EoPs']), verbo([expressed]), complemento(['eosinophil-related', 'genes,', such, as, the, eosinophil, peroxidase, and, the, major, basic, 'protein,', but, did, not, express, 'basophil/mast', 'cell-related', mast, cell, proteases])]). relacion([sujeto(['The', enforced, retroviral, expression, of, 'IL-5Ralpha', in, 'GMPs', did, not]), verbo([enhance]), complemento([the, frequency, of, eosinophil, lineage, 'read-outs,', whereas, 'IL-5Ralpha(+)', 'GMPs', displayed, normal, 'neutrophil/monocyte', differentiation, in, the, presence, of, 'IL-5', alone])]). relacion([sujeto(['Thus,', 'IL-5Ralpha', might, be]), verbo([expressed]), complemento([specifically, at, the, 'EoP', stage, as, a, result, of, commitment, into, the, eosinophil, lineage])]). relacion([sujeto(['The', newly, identified, 'EoPs', could, be, the, cellular]), verbo([target]), complemento([in, the, treatment, of, a, variety, of, disorders, mediated, by, eosinophils])]). relacion([sujeto(['The', multidrug, resistance, 'EhPgp1', gene, is, constitutively]), verbo([expressed]), complemento([in, drug, resistant, trophozoites, from, 'Entamoeba', histolytica])]). relacion([sujeto(['It']), verbo([has]), complemento([been, demonstrated, that, two, 'CCAAT/enhancer', binding, sites, located, in, the, 'EhPgp1', gene, promoter, control, its, transcriptional, activation])]). relacion([sujeto(['Further', investigations, are, currently, in, progress, to, determine, the, identity, of, these]), verbo([nuclear]), complemento([factors, and, how, they, are, interacting, with, the, 'EhPgp1', gene, promoter])]). relacion([sujeto(['Vanadium', complexes, are, known, to, possess, potent, 'insulin-mimetic', 'effects,', high, affinity, for, several, enzymes, and, anticancer, 'activity,', which, deserve]), verbo([increasing]), complemento([attention, for, application, to, biomedical, sciences])]). relacion([sujeto(['Different', vanadium, complexes]), verbo([have]), complemento([been, found, to, be, more, effective, than, the, simple, 'vanadium-(IV)', and, -, '(', 'V)', salts, in, experiments, performed, both, in, vitro, and, in, vivo])]). relacion([sujeto(['Application', of, polyoxometalates, as, potential, drugs, against, 'Herpes', 'Simplex', 'Virus', and, 'AIDS']), verbo([have]), complemento([also, increased, the, interest, to, study, the, association, between, vanadium, containing, species, and, proteins])]). relacion([sujeto(['The', aim, of, our, research, was, to, investigate, the, in, vitro, antiproliferative, activity, of, a, variety, of, 'vanadium-containing', 'compounds,', and, study, their, ability, to, interfere, with, the, molecular, interactions, between, 'GATA-1', and, 'NF-kappaB', transcription, factors, and]), verbo([target]), complemento(['DNA', 'elements,', employing, electrophoretic, mobility, shift, assays])]). relacion([sujeto(['All', of, the, used, vanadium, compounds, were]), verbo([found]), complemento([to, exhibit, antiproliferative, 'activity,', despite, with, differences, in, efficacy])]). relacion([sujeto(['Inhibition', of, 'K562', cell, growth, was, not]), verbo([associated]), complemento([with, 'differentiation,', but, with, activation, of, apoptosis])]). relacion([sujeto(['Vanadium', complexes, with, a, +, 5, oxidation, state, and, their, discrete, anionic, units, appear, essential, for, the, respective, effects, on, 'K562', 'cells;', a, +, 4, oxidation, state, appears, to, be, important, in]), verbo([inhibiting]), complemento([transcription, 'factors/DNA', interactions])]). relacion([sujeto(['Changes', in]), verbo([nuclear]), complemento([receptor, transcription, factors, '(', 'THRalpha1,', 'RORalpha4,', 'HNF4alpha,', 'NUR77),', other, transcription, factors, '(', 'GATA1,', 'AP-2alpha,', 'OCT1,', 'ATF6alpha,', 'ZFP161,', 'ZNF354A,', 'PDCD2),', and, transcription, cofactors, '(', 'PC4,', 'PCAF,', 'MTA1,', 'TCEA1,', 'JMY)', are, indicative, of, 'major,', 'co-ordinated', changes, in, transcription])]). relacion([sujeto(['Proteins']), verbo([involved]), complemento([in, 'DNA', 'repair/recombination,', ribosomal, 'RNA', 'synthesis,', 'RNA', 'processing,', nuclear, 'transport,', nuclear, 'organization,', protein, 'translation,', 'glycolysis,', lipid, 'metabolism,', several, protein, kinases, '(', 'PKCdelta,', 'MAP3K4,', 'GRK3),', as, well, as, proteins, with, no, established, functional, role, were, also, observed])]). relacion([sujeto(['The', observed, proteins]), verbo([suggest]), complemento([nuclear, regulatory, roles, for, proteins, involved, in, cytosolic, processes, such, as, glycolysis, and, fatty, acid, 'metabolism,', and, roles, in, overall, nuclear, 'structure/organization', for, proteins, previously, associated, with, meiosis, 'and/or', spermatogenesis, '(', synaptonemal, complex, proteins, 1, and, 2, '(', 'SYCP1,', 'SYCP2),', 'meiosis-specific', nuclear, structural, protein, 1, '(', 'MNS1),', 'LMNC2,', zinc, finger, protein, 99, '(', 'ZFP99))'])]). relacion([sujeto(['Proteins']), verbo([associated]), complemento([with, cytoplasmic, membrane, functions, '(', 'ACTN4,', hyaluronan, mediated, motility, receptor, '(', 'RHAMM),', 'VLDLR,', 'GRK3)', 'and/or', endocytosis, '(', 'DNM2)', were, also, seen])]). relacion([sujeto(['Comparison', with, proteins]), verbo([involved]), complemento([in, cell, 'death,', 'cancer,', and, 'testis/meiosis/spermatogenesis', suggests, 'commonalities,', which, may, reflect, fundamental, mechanisms, for, 'down-regulation', of, cellular, function])]). relacion([sujeto(['At', diagnosis, of, 't-AML,', 282, '(', 92, '%', ')', had, clonal, abnormalities]), verbo([involving]), complemento([chromosome, 5, '(', 'n=63),', chromosome, 7, '(', 'n=85),', both, chromosomes, 5, and, 7, '(', 'n=66),', recurring, balanced, rearrangements, '(', 'n=31),', or, other, clonal, abnormalities, '(', 'n=39);', 24, had, a, normal, karyotype])]). relacion([sujeto(['Patients', presenting, with, acute, leukemia, were, more, likely, to]), verbo([have]), complemento([a, balanced, rearrangement, than, those, presenting, with, myelodysplasia, '(', 28, '%', versus, 4, '%', ',', 'p<0'])]). relacion([sujeto(['To']), verbo([gain]), complemento([insights, into, the, molecular, basis, of, this, 'disease,', we, performed, gene, expression, profiling, of, 'CD34+', hematopoietic, progenitor, cells, from, 't-AML', patients])]). relacion([sujeto(['We']), verbo([found]), complemento([distinct, subtypes, of, 't-AML', that, have, characteristic, gene, expression, patterns])]). relacion([sujeto(['Common', to, each, of, the, subgroups, are, gene, expression, patterns, typical, of]), verbo([arrested]), complemento([differentiation, in, early, progenitor, cells])]). relacion([sujeto(['Leukemias', with, a, -, 5, /, 'del(5q)']), verbo([have]), complemento([a, higher, expression, of, genes, involved, in, cell, cycle, control, '(', 'CCNA2,', 'CCNE2,', 'CDC2),', checkpoints, '(', 'BUB1),', or, growth, '(', 'MYC),', and, loss, of, expression, of, the, gene, encoding, interferon, consensus, 'sequence-binding', protein, '(', 'ICSBP)'])]). relacion([sujeto(['A', second, subgroup, of, 't-AML', is, characterized, by, 'down-regulation', of, transcription, factors]), verbo([involved]), complemento([in, early, hematopoiesis, '(', 'TAL1,', 'GATA1,', and, 'EKLF)', and, overexpression, of, proteins, involved, in, signaling, pathways, in, myeloid, cells, '(', 'FLT3)', and, cell, survival, '(', 'BCL2)'])]). relacion([sujeto(['Establishing', the, molecular, pathways]), verbo([involved]), complemento([in, 't-AML', may, facilitate, the, identification, of, selectively, expressed, genes, that, can, be, exploited, for, the, development, of, targeted, therapies])]). relacion([sujeto(['It']), verbo([acts]), complemento([as, an, activator, and, repressor, of, different, target, 'genes,', for, 'example,', in, erythroid, cells, it, represses, cell, proliferation, and, early, hematopoietic, genes, while, activating, erythroid, 'genes,', yet, it, is, not, clear, how, both, of, these, functions, are, mediated])]). relacion([sujeto(['Importantly,', we, show, that, 'FOG-1']), verbo([mediates]), complemento(['GATA-1', interactions, with, the, 'MeCP1', 'complex,', thus, providing, an, explanation, for, the, overlapping, functions, of, these, two, factors, in, erythropoiesis])]). relacion([sujeto(['We', also, show, that, subsets, of, 'GATA-1', gene]), verbo([targets]), complemento([are, bound, in, vivo, by, distinct, 'complexes,', thus, linking, specific, 'GATA-1', partners, to, distinct, aspects, of, its, functions])]). relacion([sujeto(['Based', on, these, 'findings,', we]), verbo([suggest]), complemento([a, model, for, the, different, roles, of, 'GATA-1', in, erythroid, differentiation])]). relacion([sujeto(['Transcription', factor, 'GATA-1', and, its, cofactor, 'FOG-1', coordinate, erythroid, cell, maturation, by]), verbo([activating]), complemento(['erythroid-specific', genes, and, repressing, genes, associated, with, the, undifferentiated, state])]). relacion([sujeto(['Here', we, show, that, 'FOG-1']), verbo([binds]), complemento([to, the, 'NuRD', corepressor, complex, in, vitro, and, in, vivo])]). relacion([sujeto(['The', interaction, is]), verbo([mediated]), complemento([by, a, small, conserved, domain, at, the, extreme, 'N-terminus', of, 'FOG-1', that, is, necessary, and, sufficient, for, 'NuRD', binding])]). relacion([sujeto(['This', domain, defines, a, novel, repression, module]), verbo([found]), complemento([in, diverse, transcriptional, repressors])]). relacion([sujeto(['Point', mutations, near, the, 'N-terminus', of, 'FOG-1', that, abrogate, 'NuRD']), verbo([binding]), complemento([block, gene, repression, by, 'FOG-1'])]). relacion([sujeto(['Finally,', the, ability, of, 'GATA-1', to, repress, transcription, was, impaired, in, erythroid, cells]), verbo([expressing]), complemento([mutant, forms, of, 'FOG-1', that, are, defective, for, 'NuRD', binding])]). relacion([sujeto(['Deletion', of, the, 'LIM2', 'domain,', but, not, of, the, 'LIM1', 'domain,', abolished, its]), verbo([binding]), complemento([of, 'GATA', proteins])]). relacion([sujeto(['Overexpression', of, 'wild-type', 'LMO2', is, known, to]), verbo([have]), complemento([dominant, negative, inhibitory, effects, on, erythropoietic, development])]). relacion([sujeto(['Enforced', expression, of, 'LMO2', constructs, with, mutant, or, absent, 'LIM2', but, with, an, intact, 'LIM1', domain, resulted, in, fetal, 'death,', small, livers, and, 'hearts,', and]), verbo([decreased]), complemento(['hematopoiesis,', as, well, as, a, hypoplastic, thymus])]). relacion([sujeto(['DMSO-induced', erythroid, differentiation, of, the, 'MEL', cells, was]), verbo([inhibited]), complemento([by, the, overexpressed, 'LMO2', with, mutant, 'LIM2', but, not, by, the, 'LMO2', with, modified, 'LIM1'])]). relacion([sujeto(['Overexpression', of, the, 'LMO2', with, modified, 'LIM2']), verbo([inhibited]), complemento([hematopoiesis, probably, by, interfering, with, the, formation, of, the, physiological, complex, or, by, replacing, the, functional, 'LMO2', with, mutants, with, reduced, affinity, to, 'GATA', proteins])]). relacion([sujeto(['Acquired', mutations, in, the, hematopoietic, transcription, factor, 'GATA']), verbo([binding]), complemento(['protein-1', '(', 'GATA1)', are, found, in, megakaryoblasts, from, nearly, all, individuals, with, 'Down', syndrome, with, transient, myeloproliferative, disorder, '(', 'TMD,', also, called, transient, 'leukemia)', and, the, related, acute, megakaryoblastic, leukemia, '(', 'DS-AMKL,', also, called, 'DS-AML', 'M7)'])]). relacion([sujeto(['These', mutations]), verbo([lead]), complemento([to, production, of, a, variant, 'GATA1', protein, '(', 'GATA1s)', that, is, truncated, at, its, 'N', terminus])]). relacion([sujeto(['To', understand, the, biological, properties, of, 'GATA1s', and, its, relation, to, 'DS-AMKL', and, 'TMD,', we, used, gene]), verbo([targeting]), complemento([to, generate, 'Gata1', alleles, that, express, 'GATA1s', in, mice])]). relacion([sujeto(['We', show, that, the, dominant, action, of, 'GATA1s']), verbo([leads]), complemento([to, hyperproliferation, of, a, 'unique,', previously, unrecognized, yolk, sac, and, fetal, liver, 'progenitor,', which, we, propose, accounts, for, the, transient, nature, of, 'TMD', and, the, restriction, of, 'DS-AMKL', to, infants])]). relacion([sujeto(['Our', observations, raise, the, possibility, that, the]), verbo([target]), complemento([cells, in, other, leukemias, of, infancy, and, early, childhood, are, distinct, from, those, in, adult, leukemias, and, underscore, the, interplay, between, specific, oncoproteins, and, potential, target, cells])]). relacion([sujeto(['We', conclude, that, blf, plays, an, important, role, in]), verbo([regulating]), complemento([morphogenetic, movements, during, gastrulation, and, neurulation, while, its, role, in, hematopoiesis, may, be, redundant])]). relacion([sujeto(['Second,', children, with, 'Down', syndrome, who, develop, acute, megakaryoblastic, leukemia, harbor, mutations, in, 'GATA1', that]), verbo([lead]), complemento([to, the, exclusive, expression, of, a, shorter, isoform, named, 'GATA-1s'])]). relacion([sujeto(['In', 'contrast,', megakaryocytes, that]), verbo([expressed]), complemento(['V205G', 'GATA-1', exhibited, reduced, 'proliferation,', but, failed, to, undergo, maturation])]). relacion([sujeto(['These', studies, show, that, 'GATA-1', is]), verbo([required]), complemento([for, both, normal, regulation, of, proliferation, and, terminal, maturation, of, 'megakaryocytes,', and, 'further,', that, these, functions, can, be, uncoupled, by, mutations, in, 'GATA1'])]). relacion([sujeto(['Children', with, 'Down', 'Syndrome', '(', 'DS)']), verbo([have]), complemento([a, 20, -, 40, fold, increased, risk, of, developing, acute, myeloid, leukemia, '(', 'AML),', mainly, of, the, megakaryoblastic, subtype, '(', 'AMKL)'])]). relacion([sujeto(['In', 'addition,', an]), verbo([increased]), complemento([dose, of, 'RUNX1', is, suggested, as, a, basis, for, several, kinds, of, leukemias])]). relacion([sujeto(['Amplifications', of, chromosome, 21, or, the, 'RUNX1', gene, are, shown, to, be]), verbo([associated]), complemento([with, leukemias, with, lymphoid, 'lineage,', whereas, its, involvement, in, myeloid, lineage, remains, unclear])]). relacion([sujeto(['In', this, 'study,', we, generated, 'GATA-1', 'promoter-driven', 'Runx1', transgenic, '(', 'Tg)', 'mice,', which, showed, a, transient, mild]), verbo([increase]), complemento([of, megakaryocyte, 'marker-positive', myeloid, cells, but, no, spontaneous, leukemia])]). relacion([sujeto(['These', mice, were, then, crossed, with, 'BXH2', 'mice,', which]), verbo([have]), complemento([a, 'replication-competent', retrovirus, in, the, mouse, and, develop, myeloid, leukemia, due, to, insertional, mutagenesis, by, random, integration, of, the, virus])]). relacion([sujeto(['Overexpressed', 'Runx1', transgene, in, 'BXH2', mice, resulted, in, shortening, of, the, latency, of, leukemia, with]), verbo([increased]), complemento([frequency, of, megakaryoblastic, 'leukemia,', suggesting, that, increased, 'Runx1', dosage, is, leukemogenic, in, myeloid, lineage])]). relacion([sujeto(['Gene', expression, analysis, of, differentiating, hEBs, revealed, that, initiation, of, hematopoiesis, correlated, with]), verbo([increased]), complemento([levels, of, 'SCL/TAL1,', 'GATA1,', 'GATA2,', 'CD34,', 'CD31,', and, the, homeobox, 'gene-regulating', factor, 'CDX4', 'These', data, indicate, that, hematopoietic, differentiation, of, hESCs, models, the, earliest, events, of, embryonic, and, definitive, hematopoiesis, in, a, manner, resembling, human, yolk, sac, 'development,', thus, providing, a, valuable, tool, for, dissecting, the, earliest, events, in, human, 'HSPC', genesis])]). relacion([sujeto(['Hematopoiesis']), verbo([involves]), complemento([the, production, of, stem, 'cells,', followed, by, the, orchestrated, differentiation, of, the, blood, lineages])]). relacion([sujeto(['Genetic', screens, in, zebrafish]), verbo([have]), complemento([identified, mutants, with, defects, that, disrupt, specific, stages, of, hematopoiesis, and, 'vasculogenesis,', including, the, 'cloche,', spadetail, '(', 'tbx16),', moonshine, '(', 'tif1g),', 'bloodless,', and, vlad, tepes, '(', 'gata1)', mutants])]). relacion([sujeto(['These', were]), verbo([found]), complemento([to, correlate, with, the, transcriptional, program, of, hematopoietic, progenitor, 'cells,', as, well, as, of, the, 'erythroid,', 'myeloid,', and, vascular, lineages])]). relacion([sujeto(['A', specific, regulation, was]), verbo([found]), complemento([for, myeloid, 'genes,', as, they, were, more, strongly, expressed, in, vlt, mutants, compared, with, other, erythroid, mutants])]). relacion([sujeto(['A', unique, gene, expression, pattern, of, 'up-regulated', isoprenoid, synthesis, genes, was]), verbo([found]), complemento([in, cloche, and, 'scl(mo),', possibly, in, migrating, cells])]). relacion([sujeto(['Several']), verbo([reports]), complemento([suggest, that, 'GATA-1', plays, multiple, roles, in, 'survival,', 'proliferation,', and, differentiation, of, erythroid, cells])]). relacion([sujeto([5, proerythroblasts, accumulated, in, 'S', phase, and]), verbo([expressed]), complemento([lower, levels, of, 'p16(INK4A)', than, 'WT', 'ES', 'cell-derived', proerythroblasts])]). relacion([sujeto(['We', concluded, that, 'GATA-1', must, achieve, a, critical, threshold, activity, to, achieve, selective, activation, of, specific]), verbo([target]), complemento(['genes,', thereby, influencing, the, developmental, decision, of, an, erythroid, progenitor, cell, to, undergo, 'apoptosis,', 'proliferation,', or, terminal, differentiation])]). relacion([sujeto(['Less', well, defined, is, whether, 'GATA-2']), verbo([participates]), complemento([in, adult, 'stem-cell', 'regulation,', an, issue, we, addressed, using, 'GATA-2', heterozygote, mice, that, express, reduced, levels, of, 'GATA-2', in, hematopoietic, cells])]). relacion([sujeto(['While', 'GATA-2+/-', mice, demonstrated]), verbo([decreases]), complemento([in, some, 'colony-forming', 'progenitors,', the, most, prominent, changes, were, observed, within, the, 'stem-cell', compartment])]). relacion([sujeto(['Furthermore,', a, 'stem-cell-enriched', population, from, 'GATA1+/-', marrow, was, more, quiescent, and, exhibited, a, greater, frequency, of, apoptotic, cells]), verbo([associated]), complemento([with, decreased, expression, of, the, 'anti-apoptotic', gene, 'Bcl-xL'])]). relacion([sujeto(['Thus,', 'GATA-2', dose]), verbo([regulates]), complemento([adult, 'stem-cell', homeostasis, by, affecting, select, aspects, of, stem, cell, function])]). relacion([sujeto(['CC', 'Chemokine', 'Receptor', 3, '(', 'CCR3),', the, major, chemokine, receptor]), verbo([expressed]), complemento([on, 'eosinophils,', binds, promiscuously, to, several, ligands, including, eotaxins, 1, ',', 2, ',', and, 3])]). relacion([sujeto(['Even', though, the, only, cells, that, consistently, accumulate, following, eotaxin, administration, in, vivo, are, myeloid, cells, '(', primarily, 'eosinophils),', other, cell, types]), verbo([have]), complemento([recently, been, shown, to, express, 'CCR3'])]). relacion([sujeto(['It', is, therefore, important, to, elucidate, the, molecular, mechanisms]), verbo([regulating]), complemento([receptor, expression])]). relacion([sujeto(['Coupled', with, our, previous, data, implicating, exon, 1, in, 'CCR3', 'transcription,', we, hypothesized, that, transcription, factors]), verbo([bind]), complemento([to, 'exon-1'])]). relacion([sujeto(['Electrophoretic', mobility, shift, analysis, revealed, that]), verbo([nuclear]), complemento([proteins, in, eosinophilic, cells, bound, to, exon, 1])]). relacion([sujeto(['Furthermore,', antibody, interference, and, mutation, studies, demonstrated, 'GATA-1']), verbo([binding]), complemento([to, exon, 1])]). relacion([sujeto(['In', order, to, test, the, 1.6, -, kb, 'CCR3', promoter, element, '(', that, includes, exon, 1, ')', for, in, vivo, 'function,', this, region, was, used, to, generate, transgenic, mice, that]), verbo([expressed]), complemento([a, reporter, protein])]). relacion([sujeto(['Strong', transgene, expression, was, 'achieved,', with, the, pattern, of, expression]), verbo([suggesting]), complemento([a, broad, acting, promoter])]). relacion([sujeto(['The', transcription, factor, 'GATA-1']), verbo([binds]), complemento([to, 'CCR3', exon, 1])]). relacion([sujeto(['To', discover, novel, genes, potentially]), verbo([involved]), complemento([in, hematopoietic, and, vascular, 'development,', we, performed, microarray, analysis, of, more, than, 15, ',', 0, zebrafish, genes, or, expressed, sequence, tags, '(', 'ESTs)', in, clo, mutant, embryos])]). relacion([sujeto(['Dual', specificity, phosphatase, 5, '(', 'dusp5),', cadherin, 5, '(', 'cdh5;', 'VE-cadherin),', aquaporin, 8, '(', 'aqp8),', adrenomedullin, receptor, '(', 'admr),', complement, receptor, 'C1qR-like', '(', 'crl),', scavenger, receptor, class, 'F,', member, 1, '(', 'scarf1),', and, 'ETS1-like', protein, '(', 'etsrp)', were, specifically]), verbo([expressed]), complemento([in, the, vascular, endothelial, 'cells,', while, retinol, binding, protein, 4, '(', 'rbp4)', was, expressed, in, the, yolk, syncytial, layer, and, the, hypochord])]). relacion([sujeto(['Further', functional, studies, of, these, novel, genes, should, help, to, elucidate, critical, early, steps]), verbo([leading]), complemento([to, the, formation, of, vertebrate, blood, vessels])]). relacion([sujeto(['GATA', proteins, are, transcription, factors, that]), verbo([bind]), complemento(['GATA', 'DNA', elements, through, 'Cys4', structural, 'zinc-binding', domains, and, play, critical, regulatory, roles, in, neurological, and, urogenital, development, and, the, development, of, cardiac, disease])]). relacion([sujeto(['To', evaluate, 'GATA', proteins, as, potential]), verbo([targets]), complemento([for, 'lead,', spectroscopically, monitored, 'metal-binding', titrations, were, used, to, measure, the, affinity, of, 'Pb2+', for, the, 'C-terminal', 'zinc-binding', domain, from, chicken, 'GATA-1', '(', 'CF)', and, the, 'double-finger', domain, from, human, 'GATA-1', '(', 'DF)'])]). relacion([sujeto(['These', studies]), verbo([reveal]), complemento([that, 'Pb2+', forms, tight, complexes, with, cysteine, residues, in, the, 'zinc-binding', sites, in, 'GATA', 'proteins,', beta1Pb, =, 6.4, '(', +, /, -, 2.0, ')', x, 10, '(', 9, ')', 'M(-1)', for, 'CF', and, beta2, =, 6.3, '(', +, /, -, 6.3, ')', x, 10, '(', 19, ')', 'M(-2)', for, 'Pb(2+)2-DF,', and, within, an, order, of, magnitude, of, the, affinity, of, 'Zn2+', for, these, proteins])]). relacion([sujeto(['Furthermore,', 'Pb2+', was, able, to, displace]), verbo([bound]), complemento(['Zn2+', from, 'CF', and, 'DF'])]). relacion([sujeto(['Upon', addition, of, 'Pb2+,', 'GATA', shows, a]), verbo([decreased]), complemento([ability, to, bind, to, 'DNA', and, subsequently, activate, transcription])]). relacion([sujeto(['Therefore,', the, 'DNA']), verbo([binding]), complemento([and, transcriptional, activity, of, 'GATA', proteins, are, most, likely, to, be, targeted, by, 'Pb2+', in, cells, and, tissues, that, sequester, 'Pb2+', in, 'vivo,', which, include, the, brain, and, the, heart])]). relacion([sujeto(['Early', erythroblasts, from, patients, with, refractory, anemia, '(', 'RA)', and, 'RA', with, ringed, sideroblasts, '(', 'RARS)', show, constitutive, mitochondrial]), verbo([release]), complemento([of, cytochrome, c])]). relacion([sujeto(['Whereas', none, or, few, cultured, erythroid, cells, from, healthy, individuals, and, 'RA', patients]), verbo([expressed]), complemento(['MtF,', those, from, 'RARS', patients, showed, 'MtF', expression, at, an, early, 'stage,', when, cells, were, 'CD34+', and, without, morphologic, signs, of, erythroid, differentiation])]). relacion([sujeto(['The', proportion, of, 'RARS', erythroblasts, that, were, 'MtF+']), verbo([increased]), complemento([further, upon, in, vitro, maturation])]). relacion([sujeto(['Genes']), verbo([involved]), complemento([in, erythroid, differentiation, were, also, dysregulated, in, 'MDS', cells])]). relacion([sujeto(['Importantly,', 'GATA-1', expression]), verbo([increased]), complemento([during, normal, erythroid, 'maturation,', but, remained, low, in, 'MDS', 'cultures,', indicating, a, block, of, erythroid, maturation, at, the, transcriptional, level])]). relacion([sujeto(['In', 'conclusion,', aberrant, 'MtF', expression, in, 'RARS', erythroblasts, occurs, at, a, very, early, stage, of, erythroid, differentiation, and, is, paralleled, by, an, 'up-regulation', of, genes]), verbo([involved]), complemento([in, this, process])]). relacion([sujeto(['The', dominant, expression, of, 'GATA-2', gene, was]), verbo([found]), complemento([in, the, 'BMSCs', from, 'AML,', 'CML', or, normal, controls])]). relacion([sujeto(['Core']), verbo([binding]), complemento([factor, '(', 'CBF)', participates, in, specification, of, the, hematopoietic, stem, cell, and, functions, as, a, critical, regulator, of, hematopoiesis])]). relacion([sujeto(['AML1-FOG2']), verbo([retains]), complemento([a, motif, that, recruits, the, corepressor, 'C-terminal', binding, protein, '(', 'CtBP)', and, these, proteins, associate, in, a, protein, complex])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([a, central, role, for, 'CtBP', in, 'AML1-FOG2', transcriptional, repression, and, implicate, coordinated, disruption, of, the, 'AML1', and, 'GATAdevelopmental', programs, in, the, pathogenesis, of, myelodysplasia])]). relacion([sujeto(['Defects', in, the, 'X-linked', 'DNA-binding', megakaryocyte, transcription, factor, 'GATA1']), verbo([cause]), complemento([thrombocytopenia, and, abnormal, platelet, function])]). relacion([sujeto(['Here,', we, studied, platelets, from, 'GATA1-deficient', mice, and, from, a, male, patient, '(', 'S14)', with, a, bleeding, diathesis, attributed, to, a, single, amino, acid, substitution, '(', 'R216Q)', in, the, 'N-terminal', 'GATA1', zinc, finger, that, alters]), verbo([binding]), complemento([to, 'DNA'])]). relacion([sujeto(['In', both, cases, there, was, inhibition, of, aggregation, to, collagen, and]), verbo([decreased]), complemento([tyrosine, phosphorylation, of, glycoprotein, 'VI', '(', 'GPVI)-signaling', proteins])]). relacion([sujeto(['This', effect, was, more, marked, in, 'GATA1-deficient', murine, 'platelets,', where, it, was]), verbo([associated]), complemento([with, a, significant, reduction, in, surface, 'GPVI', expression])]). relacion([sujeto(['Moreover,', both, human, and, murine, 'GATA1-mutant', platelets, showed, reduced, adhesion, and, aggregate, formation, on, a, collagen, matrix, at, an, intermediate, rate, of, 'shear,', although, this, could, not, be, accounted, solely, by, the, thrombocytopenia, and, altered, 'GPVI', 'expression,', indicating, that, 'GATA1']), verbo([regulates]), complemento([additional, factors, important, for, platelet, activation, under, shear])]). relacion([sujeto(['Our', results, are, consistent, with, 'GATA1']), verbo([regulating]), complemento([some, but, not, all, pathways, of, platelet, 'activation,', leading, to, an, impairment, of, aggregate, formation, under, 'flow,', which, cannot, be, attributed, solely, to, the, thrombocytopenia])]). relacion([sujeto(['Recent', evidence]), verbo([suggests]), complemento([that, 'long-range', enhancers, and, gene, promoters, are, in, close, 'proximity,', which, might, reflect, the, formation, of, chromatin, loops])]). relacion([sujeto(['By', using, chromosome, conformation, capture, '(', 3, 'C),', we, show, that, the, hematopoietic, transcription, factor, 'GATA-1', and, its, cofactor, 'FOG-1', are]), verbo([required]), complemento([for, the, physical, interaction, between, the, 'beta-globin', locus, control, region, '(', 'LCR)', and, the, 'beta-major', globin, promoter])]). relacion([sujeto(['Kinetic', studies]), verbo([reveal]), complemento([that, 'GATA-1-induced', loop, formation, correlates, with, the, onset, of, 'beta-globin', transcription, and, occurs, independently, of, new, protein, synthesis])]). relacion([sujeto(['GATA-1', occupies, the, 'beta-major', globin, promoter, normally, in, fetal, liver, erythroblasts, from, mice, lacking, the, 'LCR,']), verbo([suggesting]), complemento([that, 'GATA-1', binding, to, the, promoter, and, 'LCR', are, independent, events, that, occur, prior, to, loop, formation])]). relacion([sujeto(['Together,', these, data, demonstrate, that, 'GATA-1', and, 'FOG-1', are, essential, anchors, for, a, 'tissue-specific', chromatin, 'loop,']), verbo([providing]), complemento([general, insights, into, 'long-range', enhancer, function])]). relacion([sujeto(['Down', syndrome, children, with, acute, megakaryocytic, leukemia, '(', 'AMkL)']), verbo([have]), complemento([higher, cure, rates, than, 'non-Down', syndrome, acute, myeloid, leukemia, '(', 'AML)', patients, treated, with, cytosine, arabinoside, '(', 'ara-C)'])]). relacion([sujeto(['Somatic', mutations, in, the, 'GATA1', transcription, factor]), verbo([have]), complemento([been, detected, exclusively, and, almost, uniformly, in, 'Down', syndrome, 'AMkL', 'patients,', suggesting, a, potential, linkage, to, the, chemotherapy, sensitivity, of, 'Down', syndrome, megakaryoblasts])]). relacion([sujeto(['Stable', transfection, of, 'wild-type', 'GATA1', cDNA, into, the, 'Down', syndrome, 'AMkL', cell, line, 'CMK', resulted, in]), verbo([decreased]), complemento(['(', 8, -, to, 17, -, 'fold)', 'ara-C', sensitivity, and, a, 'threefold-lower', generation, of, the, active, 'ara-C', metabolite, 'ara-CTP', compared, with, that, for, 'mock-transfected', 'CMK', cells])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, 'GATA1', transcriptionally, upregulates, cytidine, deaminase, and, that, the, presence, or, absence, of, 'GATA1', mutations, in, 'AML', blasts, likely, confers, differences, in, 'ara-C', sensitivities, due, to, effects, on, cytidine, deaminase, gene, 'expression,', 'which,', in, 'turn,', contributes, to, the, high, cure, rate, of, 'Down', syndrome, 'AMkL', patients])]). relacion([sujeto(['We', previously]), verbo([reported]), complemento([two, rare, neonates, without, 'DS', who, had, 'TMD,', one, of, whom, progressed, to, 'AMKL'])]). relacion([sujeto(['We', now, show, that, the, blood, cells, at, presentation, of, 'TMD', harboured, 'GATA1', genomic, 'DNA', 'mutations,']), verbo([suggesting]), complemento([a, requirement, for, trisomy, 21, in, haematopoietic, 'cells,', rather, than, other, cell, 'types,', for, development, of, 'TMD/AMKL'])]). relacion([sujeto(['Although', 'GATA-1', and, 'GATA-2', were, shown, to, be, essential, for, the, development, of, hematopoietic, cells, by, gene]), verbo([targeting]), complemento(['experiments,', they, were, also, reported, to, inhibit, the, growth, of, hematopoietic, cells])]). relacion([sujeto(['On', the, other, 'hand,', it, drastically]), verbo([inhibited]), complemento(['TPO-dependent', growth, and, 'gp130-mediated', 'growth/survival', of, 'Ba/F3'])]). relacion([sujeto(['As', for, this, 'mechanism,', we]), verbo([found]), complemento([that, both, 'GATA-1', and, 'GATA-2', directly, bound, to, 'STAT3', both, in, vitro, and, in, vivo, and, inhibited, its, 'DNA-binding', activity, in, gel, shift, assays, and, chromatin, immunoprecipitation, 'assays,', whereas, they, hardly, affected, 'STAT5', activity])]). relacion([sujeto(['In', 'addition,', endogenous, 'GATA-1', was]), verbo([found]), complemento([to, interact, with, 'STAT3', in, normal, 'megakaryocytes,', suggesting, that, 'GATA-1', may, inhibit, 'STAT3', activity, in, normal, hematopoietic, cells])]). relacion([sujeto(['Furthermore,', we]), verbo([found]), complemento([that, 'GATA-1', suppressed, 'STAT3', activity, through, its, 'N-zinc', finger, domain])]). relacion([sujeto(['Together,', these, results]), verbo([suggest]), complemento(['that,', besides, the, roles, as, transcription, 'factors,', 'GATA', family, proteins, modulate, cytokine, signals, through, 'protein-protein', 'interactions,', thereby, regulating, the, growth, and, survival, of, hematopoietic, cells])]). relacion([sujeto(['GATA-binding', motifs]), verbo([have]), complemento([been, found, in, the, regulatory, regions, of, various, 'erythroid-specific', 'genes,', suggesting, that, 'GATA-1', contributes, to, gene, regulation, during, the, entire, process, of, erythropoiesis])]). relacion([sujeto(['These', mice, were, extremely, sensitive, to, phenylhydrazine, '(', 'PHZ),', an, agent, that]), verbo([induces]), complemento(['hemolysis,', and, their, 'RBCs', were, osmotically, fragile])]). relacion([sujeto(['Importantly,', the, hemolytic, response, to, 'PHZ', was, partially, restored, by, the, simultaneous, expression, of, 'wild-type', 'GATA-1', with, the, 'DeltaNF', 'mutant,', supporting, our, contention, that, 'DeltaNF', protein, competitively]), verbo([inhibits]), complemento([the, function, of, endogenous, 'GATA-1'])]). relacion([sujeto(['These', data]), verbo([provide]), complemento([the, first, in, vivo, evidence, that, the, 'NF', domain, contributes, to, the, gene, regulation, that, is, critical, for, differentiation, and, survival, of, mature, 'RBCs', in, postnatal, erythropoiesis])]). relacion([sujeto(['Idiopathic', myelofibrosis, '(', 'IM)', is, a, disease, characterized, by, marrow, 'fibrosis,', abnormal, 'stem/progenitor', cell, 'trafficking,', and, extramedullary, hematopoiesis, frequently]), verbo([associated]), complemento([with, alterations, in, megakaryocytes, '(', 'Mks)'])]). relacion([sujeto(['The', 'relationship,', if, 'any,', between, the, pathobiologic, mechanism]), verbo([leading]), complemento([to, the, development, of, myelofibrosis, in, the, 2, animal, models, is, not, understood])]). relacion([sujeto(['In', both, animal, 'models,', development, of, myelofibrosis, was]), verbo([associated]), complemento([with, high, transforming, growth, factor, beta1, '(', 'TGF-beta1)', content, in, extracellular, fluids, of, marrow, and, spleen])]). relacion([sujeto(['These', data, indicate, that, the, 'TPO(high)', and, 'GATA-1(low)', alterations, are, linked, in, an, 'upstream-downstream', relationship, along, a, pathobiologic, pathway]), verbo([leading]), complemento([to, development, of, myelofibrosis, in, mice, 'and,', 'possibly,', of, 'IM', in, humans])]). relacion([sujeto(['GATA-1', and, 'GATA', family, member, 'GATA-2', are]), verbo([expressed]), complemento([in, erythroid, and, megakaryocytic, 'lineages,', in, which, they, play, a, crucial, role, in, cell, maturation, and, differentiation])]). relacion([sujeto(['GATA-1']), verbo([regulates]), complemento([the, transcription, of, many, specific, and, nonspecific, erythroid, genes, by, binding, to, 'DNA', at, the, consensus, sequence, 'WGATAR,', which, is, recognized, by, all, of, the, 'GATA', family, of, transcription, factors])]). relacion([sujeto(['The', 'GATA-1', protein, structure]), verbo([has]), complemento([been, well, described, and, includes, two, zinc, fingers, that, are, directly, involved, in, the, interaction, with, 'DNA', and, other, proteins, in, vivo])]). relacion([sujeto(['GATA-1', mutations, in, the, zinc, fingers, can]), verbo([cause]), complemento([deregulation, of, required, interactions, and, lead, to, severe, dysfunction, in, the, hematopoietic, system])]). relacion([sujeto(['Furthermore,', few, would]), verbo([have]), complemento([guessed, that, missense, mutations, in, 'GATA1', would, cause, inherited, blood, 'disorders,', while, acquired, mutations, would, be, found, associated, with, essentially, all, cases, of, acute, megakaryoblastic, leukemia, '(', 'AMKL)', in, children, with, 'Down', syndrome, '(', 'DS)'])]). relacion([sujeto(['In', this, 'review,', 'I', will, summarize, our, current, knowledge, of, the, role, of, 'GATA-1', in, normal, 'development,', and, discuss, how, mutations, in, 'GATA1']), verbo([lead]), complemento([to, abnormal, and, malignant, hematopoiesis])]). relacion([sujeto(['Recent', discoveries]), verbo([have]), complemento([divulged, the, 'GATA', factors, as, central, to, the, genetic, control, of, hematopoiesis])]). relacion([sujeto(['An', advanced, experimental, genetic, approach]), verbo([has]), complemento([provided, evidence, that, abnormalities, in, this, network, may, result, in, a, variety, of, blood, disorders])]). relacion([sujeto(['The', most, striking, new]), verbo([finding]), complemento([is, the, novel, pathogenesis, arising, from, 'GATA-1', dysfunction, that, leads, to, leukemia])]). relacion([sujeto(['The', authors]), verbo([report]), complemento([an, unusual, case, of, a, newborn, without, constitutional, trisomy, 21, who, developed, undifferentiated, leukemia, and, subsequently, achieved, clinical, and, molecular, remission, without, chemotherapy])]). relacion([sujeto(['Cytogenetics', and, molecular, analysis]), verbo([have]), complemento([shown, trisomy, 21, and, 'GATA1', mutation, restricted, to, leukemic, cells])]). relacion([sujeto(['Transient', megakaryoblastic, leukaemia, is]), verbo([found]), complemento([in, 10, '%', of, newborns, with, 'Down', 'syndrome,', characterized, by, constitutional, trisomy, 21])]). relacion([sujeto(['While', 'loss-of-function', analysis, shows, that, gata1, is, necessary, for, terminal, erythroid, 'differentiation,', no, study]), verbo([has]), complemento([demonstrated, that, loss, of, gata1, alters, myeloid, differentiation, during, ontogeny])]). relacion([sujeto(['Here', we]), verbo([provide]), complemento([in, vivo, evidence, that, loss, of, 'Gata1,', but, not, 'Gata2,', transforms, primitive, blood, precursors, into, myeloid, 'cells,', resulting, in, a, massive, expansion, of, granulocytic, neutrophils, and, macrophages, at, the, expense, of, red, blood, cells])]). relacion([sujeto(['In', addition, to, this, fate, 'change,', expression, of, many, erythroid, genes, was]), verbo([found]), complemento([to, be, differentially, dependent, on, 'Gata1', 'alone,', on, both, 'Gata1', and, 'Gata2,', or, independent, of, both, 'Gata', 'factors,', suggesting, that, multiple, pathways, regulate, erythroid, gene, expression])]). relacion([sujeto([1, in, the, bloodless, mutant, cloche, resulted, in, myelopoietic, 'rescue,']), verbo([providing]), complemento([intriguing, evidence, that, this, gene, can, function, in, the, absence, of, some, stem, cell, 'genes,', such, as, 'scl,', in, governing, myelopoiesis])]). relacion([sujeto(['The', 'T', to, 'C', substitution, at, position, -, 175, of, the, 'gamma-globin', gene]), verbo([has]), complemento([been, identified, in, some, individuals, with, 'non-deletion', hereditary, persistence, of, fetal, hemoglobin, '(', 'HPFH)'])]). relacion([sujeto(['In', this, 'study,', the, 'HPFH', phenotype, was, reestablished, in, transgenic, mice, carrying, the, 'mu\'LCRAgamma(-175)psibetadeltabeta', 'construct,', which, contained, a, 3.1, -, kb, 'mu\'LCR', cassette, linked, to, a, 29, -, kb, fragment, from, the, 'Agamma-to', 'beta-globin', gene, with, the, natural, chromosome, arrangement, but, with, the, -, 175, 'mutation,', which]), verbo([provided]), complemento([evidence, for, this, single, mutation, as, the, cause, of, this, form, of, 'HPFH'])]). relacion([sujeto(['In', vitro, experiments, proved, that, the, -, 175, mutation, significantly, reduced]), verbo([binding]), complemento([of, 'Oct-1', but, not, 'GATA-1,', whereas, the, -, 173, mutation, dramatically, decreased, binding, of, 'GATA-1', but, not, 'Oct-1'])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, abrogation, of, either, 'GATA-1', or, 'Oct-1', binding, to, this, promoter, region, may, result, in, the, 'HPFH', phenotype])]). relacion([sujeto(['An', in, vivo, footprinting, assay, revealed, that, either, the, -, 175, mutation, or, the, -, 173, mutation, significantly]), verbo([decreased]), complemento([overall, protein, binding, to, this, promoter, region, in, adult, erythrocytes, of, transgenic, mice])]). relacion([sujeto(['Up', to, seven, mammalian, 'DYRK', isoforms]), verbo([have]), complemento([been, 'reported,', but, only, the, 'DYRK1A', gene, '(', and, its, 'products)', has, been, well, characterized])]). relacion([sujeto(['In', 'addition,', a, 1930, -, bp, 'DYRK3', promoter, drives, erythroid, expression, and, transcript, expression, is]), verbo([inhibited]), complemento([sharply, on, 'GATA1-induced', 'G1E', cell, differentiation])]). relacion([sujeto(['We']), verbo([have]), complemento([recently, reported, that, 'Cdc6', levels, are, maintained, in, megakaryoblastic, 'HEL', 'cells,', but, severely, downregulated, by, ectopic, expression, of, transcriptional, repressor, 'Drosophila', melanogaster, escargot])]). relacion([sujeto(['Ectopic', 'Escargot', could]), verbo([bind]), complemento([this, regulatory, element, in, vitro, and, endogenous, 'GATA-1', and, 'E2A', formed, specific, complexes, in, megakaryoblastic, cells, as, well, as, in, primary, megakaryocytes])]). relacion([sujeto(['Altogether,', these, data]), verbo([suggest]), complemento([that, cdc6, expression, could, be, actively, maintained, during, megakaryocytic, differentiation, through, transcriptional, mechanisms, involving, specific, 'cis-', and, 'trans-regulatory', elements])]). relacion([sujeto(['We']), verbo([found]), complemento([that, 'GATA-1', gene, knockdown, female, '(', 'GATA-1'])]). relacion([sujeto([5, /, 'X)', mice, frequently, develop, a, hematopoietic, disorder, resembling, myelodysplastic, syndrome, that, is, characterized, by, the, accumulation, of, progenitors]), verbo([expressing]), complemento([low, levels, of, 'GATA-1'])]). relacion([sujeto(['In', the, hematopoietic, progenitors, with, the, latter, 'allele,', 'low-level', 'GATA-1', expression, is, sufficient, to, support, survival, and, proliferation, but, not, 'differentiation,']), verbo([leading]), complemento([to, the, accumulation, of, progenitors, that, are, easily, targeted, by, oncogenic, stimuli])]). relacion([sujeto(['Since', such, leukemia]), verbo([has]), complemento([not, been, observed, in, 'GATA-1-null/X', mutant, 'mice,', we, conclude, that, the, residual, 'GATA-1', activity, in, the, knockdown, mice, contributes, to, the, development, of, the, malignancy])]). relacion([sujeto(['This', de, novo, model, recapitulates, the, acute, crisis]), verbo([found]), complemento([in, preleukemic, conditions, in, humans])]). relacion([sujeto(['A', proliferation, 'marker,', proliferating, cell]), verbo([nuclear]), complemento([antigen, '(', 'PCNA),', a, 'Sertoli', cell, specific, transcription, 'factor,', 'GATA-1', and, the, male, germ, cell, 'specific,', 'RNA', binding, motif, '(', 'RBM),', were, used, to, identify, different, cellular, populations, during, postnatal, development, of, the, mouse, testis])]). relacion([sujeto(['PCNA', was]), verbo([expressed]), complemento([in, 'pre-Sertoli', and, germ, cells, on, the, day, of, birth])]). relacion([sujeto(['Both', 'pre-meiotic', germ, cells, and, spermatocytes]), verbo([expressed]), complemento(['RBM', throughout, postnatal, development])]). relacion([sujeto(['From', 42, days, 'onward,', there, was, a, dramatic]), verbo([decrease]), complemento([in, 'RBM', expression, in, individual, 'pre-meiotic', and, meiotic, germ, cells])]). relacion([sujeto(['The', majority, of, germ, cells, start, active, proliferation, once, they]), verbo([have]), complemento([migrated, to, the, basement, membrane, or, immediately, before])]). relacion([sujeto(['RBM', is, more, highly]), verbo([expressed]), complemento([during, the, first, wave, of, spermatogenesis, versus, subsequent, 'waves,', suggesting, that, there, may, be, a, change, in, the, activity, of, 'RBM'])]). relacion([sujeto(['In', vitro, studies]), verbo([have]), complemento([implicated, the, 'Lyn', tyrosine, kinase, in, erythropoietin, signaling])]). relacion([sujeto(['In', this, 'study,', we, show, that, 'J2E', erythroid, cells, lacking, 'Lyn']), verbo([have]), complemento([impaired, signaling, and, reduced, levels, of, transcription, factors, 'STAT5a,', 'EKLF', and, 'GATA-1'])]). relacion([sujeto(['Since', mice, lacking, 'STAT5,', 'EKLF', or, 'GATA-1']), verbo([have]), complemento([red, cell, 'abnormalities,', this, study, also, examined, the, erythroid, compartment, of, 'Lyn(-/-)', mice])]). relacion([sujeto(['Given', the, simplicity, of, the, 'DNA', sequence, that]), verbo([mediates]), complemento([binding, of, 'GATA', transcription, 'factors,', 'GATA', motifs, reside, throughout, chromosomal, 'DNA'])]). relacion([sujeto(['However,', chromatin, immunoprecipitation, analysis]), verbo([has]), complemento([revealed, that, 'GATA-1', discriminates, exquisitely, among, these, sites])]). relacion([sujeto(['We']), verbo([have]), complemento([used, high, resolution, chromatin, immunoprecipitation, to, show, that, 'GATA-1', and, 'GATA-2', occupy, two, additional, 'regions,', -, 3.9, and, -, 1.8, kb, of, the, 'GATA-2', locus])]). relacion([sujeto(['Activation', of, an, estrogen, receptor, fusion, to, 'GATA-1', '(', 'ER-GATA-1)']), verbo([induced]), complemento([similar, kinetics, of, 'ER-GATA-1', occupancy, and, 'GATA-2', displacement, at, the, sites])]). relacion([sujeto(['Transient', transfection, analysis]), verbo([provided]), complemento([evidence, that, the, -, 3.9, -, kb, region, functions, distinctly, from, the, -, 2.8, -, and, -, 1.8, -, kb, regions])]). relacion([sujeto(['We', propose, that, 'GATA-2', transcription, is]), verbo([regulated]), complemento([via, the, collective, actions, of, complexes, assembled, at, the, -, 2.8, -, and, -, 1.8, -, kb, 'regions,', which, share, similar, 'properties,', and, through, a, qualitatively, distinct, activity, of, the, -, 3.9, -, kb, complex])]). relacion([sujeto(['Blood', group, 'Duffy', gene, '(', 'FY)', promoter, in, 'Duffy-negative', individuals, contains, a, point, mutation, in, the, 'GATA1', 'protein-binding', 'motif,', which, was]), verbo([suggested]), complemento([to, be, responsible, for, erythroid, suppression, of, 'FY'])]). relacion([sujeto(['Transgenic', mice, with, 'FY', from, 'Duffy-positive', phenotype]), verbo([expressed]), complemento(['Duffy', protein, both, in, red, blood, cells, '(', 'RBCs)', and, 'non-erythroid', tissues])]). relacion([sujeto(['Transgenic', mice, with, 'FY', from, 'Duffy-negative', phenotype, did, not]), verbo([express]), complemento(['Duffy', protein, in, 'RBCs,', but, it, was, expressed, in, 'non-erythroid', tissues])]). relacion([sujeto(['Fli-1', and, 'GATA-1', transcription, factors, are]), verbo([required]), complemento([for, development, of, megakaryocytes, and, promoter, analysis, has, defined, in, vitro, functional, binding, sites, for, these, factors, in, several, megakaryocytic, 'genes,', including, 'GPIIb,', 'GPIX,', and, 'C-MPL'])]). relacion([sujeto(['Whereas', 'GPIIb', is]), verbo([expressed]), complemento([in, both, 'Meg-01', and, 'CMK11-5', 'cells,', 'GPIX', and, 'C-MPL', are, only, expressed, in, the, more, differentiated, 'CMK11-5', cells])]). relacion([sujeto(['Thus,', in, vivo, occupancy, by, an, 'Ets', factor, is, not, sufficient, to]), verbo([promote]), complemento([transcription, of, some, megakaryocytic, genes])]). relacion([sujeto(['GATA-1', and, 'Fli-1', are, both]), verbo([expressed]), complemento([in, 'CMK11-5', cells, and, 'co-occupy', the, 'GPIX', and, 'C-MPL', promoters])]). relacion([sujeto(['Transcription', of, all, three, megakaryocytic, genes, is, correlated, with, the, presence, of, acetylated, histone, 'H3', and]), verbo([phosphorylated]), complemento(['RNA', polymerase, 'II', on, their, promoters])]). relacion([sujeto(['We', also, show, that, exogenous, expression, of, 'GATA-1', in, 'Meg-01', cells]), verbo([leads]), complemento([to, the, expression, of, endogenous, 'c-mpl', and, gpIX, mRNA])]). relacion([sujeto(['Whereas', 'GPIIb,', 'GPIX,', and, 'C-MPL', are, direct]), verbo([target]), complemento([genes, for, 'Fli-1,', both, 'Fli-1', and, 'GATA-1', are, required, for, formation, of, an, active, transcriptional, complex, on, the, 'C-MPL', and, 'GPIX', promoters, in, vivo])]). relacion([sujeto(['We']), verbo([have]), complemento([now, identified, a, region, 3, '\'', of, the, core, promoter, that, contains, a, 'DNase', 'I', hypersensitive, site, and, directs, high, 'level,', 'erythroid-specific', expression, in, reporter, 'gene/transfection', assays])]). relacion([sujeto(['Both', 'GATA-1', sites, were]), verbo([required]), complemento([for, full, 'activity,', suggesting, that, elements, binding, to, each, site, interact, in, a, combinatorial, manner])]). relacion([sujeto(['These', results, demonstrate, that, a, region, 3, '\'', of, the, 'alpha-spectrin', core, promoter, contains, a, 'GATA-1-dependent', positive, regulatory, element, that, is]), verbo([required]), complemento([in, its, proper, genomic, orientation])]). relacion([sujeto(['This', is, an, excellent, candidate, region, for, mutations]), verbo([associated]), complemento([with, decreased, 'alpha-spectrin', gene, expression, in, patients, with, hereditary, spherocytosis, and, hereditary, pyropoikilocytosis])]). relacion([sujeto(['Although', physicians]), verbo([have]), complemento([known, for, many, decades, that, children, with, 'Down', syndrome, are, predisposed, to, developing, transient, myeloproliferative, disorder, '(', 'TMD)', and, acute, megakaryoblastic, leukemia, '(', 'AMKL),', many, questions, regarding, these, disorders, remain, unresolved])]). relacion([sujeto(['First,', what, is, the, relationship, between, 'TMD', and, 'AMKL?', 'Second,', what, specific, genetic, alterations, contribute, to, the, leukemic, 'process?', 'Finally,', what, factors]), verbo([lead]), complemento([to, the, increased, predisposition, to, these, myeloid, 'disorders?', 'In', this, review, 'I', will, summarize, important, new, insights, into, the, biology, of, 'TMD', and, 'AMKL', gained, from, the, recent, discovery, that, 'GATA1,', a, gene, that, encodes, an, essential, hematopoietic, transcription, 'factor,', is, mutated, in, the, leukemic, blasts, from, nearly, all, patients, with, these, malignancies])]). relacion([sujeto(['Future', research, aimed, at, defining, the, activity, of, mutant, 'GATA-1', protein, and, identifying]), verbo([interacting]), complemento([factors, encoded, by, chromosome, 21, will, likely, lead, to, an, even, greater, understanding, of, this, intriguing, leukemia])]). relacion([sujeto(['It']), verbo([has]), complemento([been, recognized, that, chromosomal, abnormalities, in, childhood, 'leukemia,', are, linked, to, both, leukemogenesis, and, segregate, patients, into, prognostic, treatment, groups])]). relacion([sujeto(['This', is, best, exemplified, in, cases, of, children, with, 'Down', syndrome, '(', 'DS),', who]), verbo([have]), complemento([significantly, higher, risks, of, developing, leukemia, compared, to, 'non-DS', children, and, distinctive, treatment, 'outcomes,', particularly, in, cases, of, acute, myeloid, leukemia, '(', 'AML)'])]). relacion([sujeto(['The', high, 'event-free', survival, '(', 'EFS)', rates, of, 'DS', 'AML', patients, and, in, 'particular,', patients, with, megakaryocytic, leukemia, '(', 'AMkL),', at, least, in, part, reflects, an]), verbo([increased]), complemento([sensitivity, to, cytosine, arabinoside, '(', 'ara-C)', secondary, to, increased, expression, of, the, chromosome, 21, -, localized, 'gene,', 'cystathionine-beta-synthase,', and, potentially, global, mechanisms, which, increase, the, susceptibility, of, cells, to, undergo, apoptosis])]). relacion([sujeto(['Somatic', mutations, of, the, 'X-linked', transcription, factor, 'gene,', 'GATA1,']), verbo([have]), complemento([been, detected, uniformly, and, exclusively, in, 'DS', 'AMkL', 'cases,', which, may, lead, to, altered, expression, of, 'GATA1', target, genes, and, alter, the, metabolism, of, drugs, including, 'ara-C'])]). relacion([sujeto(['This', is, on, account, of]), verbo([increased]), complemento([intracellular, transport, of, 'MTX', via, the, reduced, folate, carrier, '(', 'RFC)', whose, gene, is, localized, to, chromosome, 21, and, may, also, account, for, the, increased, 'MTX-associated', toxicity, of, 'DS', 'ALL', patients])]). relacion([sujeto(['Microarray', technology, should]), verbo([lead]), complemento([to, the, identification, of, additional, gene, targets, linked, to, the, treatment, response, of, specific, cytogenetic, leukemia, subgroups])]). relacion([sujeto(['Infants', with, constitutional, trisomy, 21, are, at]), verbo([increased]), complemento([risk, of, developing, transient, and, acute, megakaryoblastic, leukemia, '(', 'AMKL)'])]). relacion([sujeto(['Mutations', in, 'GATA1']), verbo([have]), complemento([been, identified, in, trisomy, 21, patients, with, 'AMKL,', and, this, lesion, is, thought, to, be, an, initial, event, by, virtue, of, its, presence, during, transient, leukemia])]). relacion([sujeto(['We']), verbo([report]), complemento([a, phenotypically, normal, infant, with, tetrasomy, 21, transient, 'leukemia,', 'GATA1', mutation, within, exon, 2, ',', and, trisomy, 21, mosaicism, restricted, to, the, hematopoietic, tissue])]). relacion([sujeto(['Embryonic', stem, '(', 'ES)', cells]), verbo([have]), complemento([the, potential, to, serve, as, an, alternative, source, of, hematopoietic, precursors, for, transplantation, and, for, the, study, of, hematopoietic, cell, development])]). relacion([sujeto(['The', hES, 'cell-derived', 'CD34+', cells, were, highly, enriched, in, 'colony-forming', 'cells,', cells]), verbo([expressing]), complemento(['hematopoiesis-associated', genes, 'GATA-1,', 'GATA-2,', 'SCL/TAL1,', and, 'Flk-1,', and, retained, clonogenic, potential, after, in, vitro, expansion])]). relacion([sujeto(['Most', studies]), verbo([have]), complemento([only, examined, the, core, region, of, 'HS-2'])]). relacion([sujeto(['In', this, 'study,', using, an, electrophoretic, mobility, shift, assay, '(', 'EMSA)', and, 'DNase', 'I', 'footprinting,', we, confirmed, that, 'GATA-1']), verbo([binds]), complemento([in, vitro, at, the, 3, '\'', -, end, of, 'HS-2'])]). relacion([sujeto(['An', additional, 'GATA-1', site, was]), verbo([found]), complemento([to, bind, 'GATA-1', in, vitro, at, a, site, positioned, 40, bp, upstream])]). relacion([sujeto(['DNA-protein', interactions, were, examined, in, three, distal, and, one, proximal, promoter, elements, in]), verbo([nuclear]), complemento([extracts, belonging, to, neuronal, and, 'non-neuronal', cells])]). relacion([sujeto(['Characterization', of, the, 'APP', regulatory, 'region\'s', interaction, with, cell, 'type-specific']), verbo([nuclear]), complemento(['factor(s)', is, important, to, understand, 'tissue-specific', expression, of, 'APP', seen, in, 'AD', subjects])]). relacion([sujeto(['Hematopoiesis', is, precisely, orchestrated, by, 'lineage-specific', 'DNA-binding', proteins, that]), verbo([regulate]), complemento([transcription, in, concert, with, coactivators, and, corepressors])]). relacion([sujeto(['We']), verbo([report]), complemento([that, mon, encodes, the, zebrafish, ortholog, of, mammalian, transcriptional, intermediary, factor, 1, gamma, '(', 'TIF1gamma)', '(', or, 'TRIM33),', a, member, of, the, 'TIF1', family, of, coactivators, and, corepressors])]). relacion([sujeto(['During', 'development,', hematopoietic, progenitor, cells, in, mon, mutants, fail, to]), verbo([express]), complemento([normal, levels, of, hematopoietic, transcription, 'factors,', including, 'gata1,', and, undergo, apoptosis])]). relacion([sujeto(['Transplantation', studies]), verbo([reveal]), complemento([that, tif1gamma, functions, in, a, 'cell-autonomous', manner, during, the, differentiation, of, erythroid, precursors])]). relacion([sujeto(['Studies', in, murine, erythroid, cell, lines, demonstrate, that, 'Tif1gamma', protein, is, localized, within, novel]), verbo([nuclear]), complemento(['foci,', and, expression, decreases, during, erythroid, cell, maturation])]). relacion([sujeto(['Although', 'Jun', upregulation, and, activation]), verbo([have]), complemento([been, established, as, critical, to, 'oncogenesis,', the, relevant, downstream, pathways, remain, incompletely, characterized])]). relacion([sujeto(['In', this, 'study,', we]), verbo([found]), complemento([that, 'c-Jun', blocks, erythroid, differentiation, in, primary, human, hematopoietic, progenitors, 'and,', 'correspondingly,', that, 'Jun', factors, block, transcriptional, activation, by, 'GATA-1,', the, central, regulator, of, erythroid, differentiation])]). relacion([sujeto(['Mutagenesis', of, 'c-Jun']), verbo([suggested]), complemento([that, its, repression, of, 'GATA-1', occurs, through, a, transcriptional, mechanism, involving, activation, of, downstream, genes])]). relacion([sujeto(['Furthermore,', transduction, of, 'HERP2', into, primary, human, hematopoietic, progenitors]), verbo([inhibited]), complemento([erythroid, differentiation])]). relacion([sujeto(['Furthermore,', these, results, establish, a, connection, between, the, 'Notch', signaling, 'pathway,', of, which, the, 'HERP', factors, are, a, critical, 'component,', and, the, 'GATA', 'family,', which]), verbo([participates]), complemento([in, programming, of, cellular, differentiation])]). relacion([sujeto(['Hemoglobin', production, during, differentiation, was, followed, by, a, significant]), verbo([increase]), complemento([in, 'GSTP1-1', mRNA, '(', 1.7, -, 'fold,', 'P', &, 'lt;', 0.01, ')', and, protein, '(', 1.2, -, 'fold,', 'P', &, 'lt;', 0.01, ')', after, 4, days, of, induction])]). relacion([sujeto(['This']), verbo([increase]), complemento([in, mRNA, production, was, not, due, to, transcriptional, 'up-regulation', by, 'GATA-1', previously, shown, to, regulate, 'GSTP1-1', during, erythroid, and, megakaryocytic, differentiation])]). relacion([sujeto(['Moreover,', a, drastic]), verbo([decrease]), complemento([in, 'differentiation-specific', 'GATA-1', mRNA, expression, was, correlated, to, a, reduction, in, 'GATA-1', promoter, binding, activity])]). relacion([sujeto(['Neither', 'AP-1', nor, 'NF-kappaB', transcription, factor]), verbo([binding]), complemento([activities, could, provide, an, explanation, to, the, 'GSTP1-1', mRNA, overexpression, in, 'hemin-treated', cells])]). relacion([sujeto(['In', this, 'paper,', we]), verbo([report]), complemento([new, observations, related, to, the, mechanism, of, the, negative, regulation, of, the, important, adult, 'beta-globin', gene, in, the, erythroid, cells, at, the, 'embryonic-fetal', stage, of, their, development])]). relacion([sujeto(['We', focused, on, the, role, of, the, silencer, 'II', region, located, upstream, of, the, 'beta-globin', 'gene,', which, along, with, its, cognate]), verbo([binding]), complemento([protein, 'BP1,', negatively, regulates, 'beta-globin', transcription])]). relacion([sujeto(['We', prepared, plasmid, constructs, containing, the, 'wild-type', silencer, 'II', 'sequence,', a, mutated, silencer, 'II', 'sequence,', or, a, mutated, control, sequence, in, the, 'beta-globin', promoter, 690, -, bp, 'insert,', which, in, turn, was, linked, to, an]), verbo([enhanced]), complemento([green, fluorescent, protein, '(', 'EGFP)', reporter, gene])]). relacion([sujeto(['Flow', cytometry, and, fluorescence, digital, imaging, showed, about, threefold]), verbo([increase]), complemento([in, the, 'beta-globin', promoter, activity, of, the, mutated, silencer, 'II', construct])]). relacion([sujeto(['Introduction', of, a, small, interfering, 'RNA', '(', 'siRNA)', complementary, to, 'BP1', into, the, cells]), verbo([caused]), complemento([a, 75, '%', decrease, in, 'BP1', expression, and, a, simultaneous, approximately, 40, '%', elevation, of, 'beta-globin', promoter, activity, as, well, as, an, increase, in, 'beta-globin', mRNA, 'levels,', as, compared, with, controls])]). relacion([sujeto(['A', better, understanding, of, this, mechanism, may, lay, the, groundwork, for, novel, gene, therapy, approaches, to]), verbo([inhibit]), complemento([the, expression, of, abnormal, structural, variants, of, adult, beta, 'globin,', such, as, sickle, hemoglobin])]). relacion([sujeto(['Transcription', factor, 'GATA-1', is]), verbo([required]), complemento([for, 'erythropoiesis,', yet, its, full, actions, are, unknown])]). relacion([sujeto(['First,', the, large, number, of, genes]), verbo([responding]), complemento([quickly, to, restoration, of, 'GATA-1', extends, the, repertoire, of, its, potential, targets])]). relacion([sujeto(['Third,', 'up-regulation', of, some, known, 'GATA-1']), verbo([targets]), complemento([was, 'delayed,', suggesting, that, auxiliary, factors, are, required])]). relacion([sujeto(['For', 'example,', induction, of, the, direct, 'GATA-1']), verbo([target]), complemento([gene, beta, major, globin, was, late, 'and,', 'surprisingly,', required, new, protein, synthesis])]). relacion([sujeto(['In', 'contrast,', the, gene, encoding, 'Fog1,', which, cooperates, with, 'GATA-1', in, beta, globin, 'transcription,', was, rapidly]), verbo([induced]), complemento([independently, of, protein, synthesis])]). relacion([sujeto(['The', block, in, maturation, includes, failure, to, properly, organize, alpha, granules, because, von, 'Willebrand', factor, is, barely, detectable, in, mutant, 'MKs,', and, 'P-selectin,', although, normally, 'expressed,', is]), verbo([found]), complemento([frequently, associated, with, the, demarcation, membrane, system, '(', 'DMS)', instead, of, within, granules])]). relacion([sujeto(['The', 'neutrophil-embedded', 'GATA-1(low)', 'MKs']), verbo([have]), complemento([morphologic, features, '(', high, electron, density, and, negativity, to, 'TUNEL', 'staining)', compatible, with, those, of, cells, dying, from, 'para-apoptosis'])]). relacion([sujeto(['We']), verbo([suggest]), complemento([that, such, an, increased, and, pathologic, neutrophil, emperipolesis, may, represent, one, of, the, mechanisms, leading, to, myelofibrosis, by, releasing, fibrogenic, 'MK', cytokines, and, neutrophil, proteases, in, the, microenvironment])]). relacion([sujeto(['We']), verbo([have]), complemento([determined, the, transcription, start, site, of, the, human, 'Gfi-1B', gene, and, located, its, first, 'non-coding', exon, approximately, 7.82, kb, upstream, of, the, first, coding, exon])]). relacion([sujeto(['The', genomic, sequence, preceding, this, first, 'non-coding', exon]), verbo([has]), complemento([been, identified, to, be, its, 'erythroid-specific', promoter, region, in, 'K562', cells])]). relacion([sujeto(['Using', 'gel-shift', and, chromatin, immunoprecipitation, '(', 'ChIP)', 'assays,', we]), verbo([have]), complemento([demonstrated, that, 'NF-Y', and, 'GATA-1', directly, participate, in, transcriptional, activation, of, the, 'Gfi-1B', gene, in, 'K562', cells])]). relacion([sujeto(['Ectopic', expression, of, 'GATA-1', markedly]), verbo([stimulates]), complemento([the, activity, of, the, 'Gfi-1B', promoter, in, a, 'non-erythroid', cell, line, 'U937'])]). relacion([sujeto(['Interestingly,', our, results]), verbo([have]), complemento([indicated, that, this, 'GATA-1-mediated', 'trans-activation', is, dependent, on, 'NF-Y', binding, to, the, 'CCAAT', site])]). relacion([sujeto(['From', analysis, of, a, limited, number, of]), verbo([conserved]), complemento([gene, 'loci,', sequence, comparison, has, proved, a, robust, and, efficient, way, to, locate, 'cis-elements'])]). relacion([sujeto(['Human', and, mouse, 'GATA1', genes, encode, a, critical, hematopoietic, transcription, factor]), verbo([conserved]), complemento([in, expression, and, function])]). relacion([sujeto(['Proper', control, of, 'GATA1', transcription, is, critical, in]), verbo([regulating]), complemento([myeloid, lineage, specification, and, maturation])]). relacion([sujeto(['Here,', we, compared, sequence, and, systematically, mapped, position, of, 'DNase', 'I', hypersensitive, 'sites,', acetylation, status, of, histone, 'H3/H4,', and, in, vivo]), verbo([binding]), complemento([of, transcription, factors, over, approximately, 120, kilobases, flanking, the, human, 'GATA1', gene, and, the, corresponding, region, in, mice])]). relacion([sujeto(['Despite', lying, in, approximately, 10, megabase, '(', 'Mb)']), verbo([conserved]), complemento([syntenic, 'segment,', the, chromatin, structures, of, the, 2, homologous, loci, are, strikingly, different])]). relacion([sujeto(['The', 2, previously, unidentified, hematopoietic, 'cis-elements,', one, in, each, 'species,', are, not]), verbo([conserved]), complemento([in, position, and, sequence, and, have, enhancer, activity, in, erythroid, cells])]). relacion([sujeto(['In', 'vivo,', they, both]), verbo([bind]), complemento([the, transcription, factors, 'GATA1,', 'SCL,', 'LMO2,', and, 'Ldb1'])]). relacion([sujeto(['These', findings]), verbo([suggest]), complemento([that, some, 'cis-elements', regulating, human, and, mouse, 'GATA1', genes, differ])]). relacion([sujeto(['We']), verbo([have]), complemento([previously, shown, that, gamma, interferon, '(', 'IFN-gamma)', induction, of, 'HLA-E', gene, transcription, is, mediated, through, a, distinct, 'IFN-gamma-responsive', 'element,', the, 'IFN', response, region, '(', 'IRR),', in, all, cell, types, studied])]). relacion([sujeto(['We']), verbo([have]), complemento([now, identified, and, characterized, a, cell, 'type-restricted', enhancer, of, 'IFN-gamma-mediated', induction, of, 'HLA-E', gene, 'transcription,', designated, the, upstream, interferon, response, region, '(', 'UIRR),', which, is, located, immediately, upstream, of, the, 'IRR'])]). relacion([sujeto(['The', 'UIRR']), verbo([mediates]), complemento([a, 'three-', to, eightfold, enhancement, of, 'IFN-gamma', induction, of, 'HLA-E', transcription, in, some, cell, lines, but, not, in, 'others,', and, it, functions, only, in, the, presence, of, an, adjacent, 'IRR'])]). relacion([sujeto(['The', 'UIRR', contains, a, variant, 'GATA']), verbo([binding]), complemento([site, '(', 'AGATAC)', that, is, critical, to, both, 'IFN-gamma', responsiveness, and, to, the, formation, of, a, specific, binding, complex, containing, 'GATA-1', in, 'K562', cell, nuclear, extracts])]). relacion([sujeto(['The']), verbo([binding]), complemento([of, 'GATA-1', to, this, site, in, response, to, 'IFN-gamma', was, confirmed, in, vivo, in, a, chromatin, immunoprecipitation, assay])]). relacion([sujeto(['Forced', expression, of, 'GATA-1', in, nonexpressing, 'U937', cells, resulted, in, a, 'four-', to, fivefold, enhancement, of, the, 'IFN-gamma', response, from, 'HLA-E', promoter, constructs, containing, a, 'wild-type', but, not, a, 'GATA-1', mutant, 'UIRR', sequence, and]), verbo([increased]), complemento([the, 'IFN-gamma', response, of, the, endogenous, 'HLA-E', gene])]). relacion([sujeto(['Knockdown', of, 'GATA-1', expression, in, 'K562', cells, resulted, in, a, approximately, 4, -, fold]), verbo([decrease]), complemento([in, the, 'IFN-gamma', response, of, the, endogenous, 'HLA-E', 'gene,', consistent, with, loss, of, the, increase, in, 'IFN-gamma', response, of, 'HLA-E', 'promoter-driven', constructs, containing, the, 'UIRR', in, 'wild-type', 'K562', cells])]). relacion([sujeto(['Coexpression', of, 'wild-type', and, mutant, adenovirus, 'E1a', proteins, that, sequester, 'p300/CBP', eliminated, 'IFN-gamma-mediated', enhancement, through, the, 'UIRR,', but, only, partially, reduced, induction, through, the, 'IRR,', implicating, 'p300/CBP']), verbo([binding]), complemento([to, 'Stat-1alpha', at, the, 'IRR', in, the, recruitment, of, 'GATA-1', to, mediate, the, cooperation, between, the, 'UIRR', and, 'IRR'])]). relacion([sujeto(['The', genetic, 'lesion(s)', underlying, chronic, idiopathic, 'myelofibrosis,', as, well, as, the, mechanisms]), verbo([leading]), complemento([to, the, typical, 'fibro-osteosclerotic', changes, of, the, bone, marrow, 'microenvironment,', are, still, undefined])]). relacion([sujeto(['Recently,', animal, models, of, the, disease]), verbo([have]), complemento([been, described])]). relacion([sujeto(['We', will, briefly, review, the, characteristics, of, these, 'models,', the, 'thrombopoietin-overexpressing', mice, and, the, 'GATA-1(low)', mice, '(', mice, deficient, for, 'GATA-1', expression, in, 'megakaryocytes),', and, illustrate, how, they]), verbo([provided]), complemento([insights, into, pathogenetic, mechanisms, of, 'myelofibrosis,', with, special, regard, to, the, role, of, abnormal, megakaryocyte, proliferation, and, maturation])]). relacion([sujeto(['How', does, an, emerging, transcriptional, programme]), verbo([regulate]), complemento([individual, genes, as, stem, cells, undergo, lineage, 'commitment,', differentiation, and, 'maturation?', 'To', answer, 'this,', we, have, analysed, the, dynamic, 'protein/DNA', interactions, across, 130, kb, of, chromatin, containing, the, mouse, 'alpha-globin', cluster, in, cells, representing, all, stages, of, differentiation, from, stem, cells, to, mature, erythroblasts])]). relacion([sujeto(['In', committed, erythroid, 'progenitors,', 'GATA-2', is, replaced, by, 'GATA-1', and]), verbo([binding]), complemento([is, extended, to, additional, sites, including, the, 'alpha-globin', promoters])]). relacion([sujeto(['Both', 'GATA-1', and, 'GATA-2', nucleate, the]), verbo([binding]), complemento([of, various, protein, complexes, including, 'SCL/LMO2/E2A/Ldb-1', and, 'NF-E2'])]). relacion([sujeto(['Changes', in, 'protein/DNA']), verbo([binding]), complemento([are, accompanied, by, sequential, alterations, in, 'long-range', histone, acetylation, and, methylation])]). relacion([sujeto(['The', recruitment, of, polymerase, 'II,', which, ultimately]), verbo([leads]), complemento([to, a, rapid, increase, in, 'alpha-globin', 'transcription,', occurs, late, in, maturation])]). relacion([sujeto(['These', studies]), verbo([provide]), complemento([detailed, evidence, for, the, more, general, hypothesis, that, commitment, and, differentiation, are, primarily, driven, by, the, sequential, appearance, of, key, transcriptional, 'factors,', which, bind, chromatin, at, 'specific,', 'high-affinity', sites])]). relacion([sujeto(['Recently,', it, was, demonstrated, that, 'CRMP-2']), verbo([binds]), complemento([to, tubulin, heterodimers, to, promote, microtubule, assembly, that, is, critical, for, axonal, differentiation, and, growth, during, development])]). relacion([sujeto(['Here', we, show, that, glial, cell, 'line-derived', neurotrophic, factor, '(', 'GDNF)']), verbo([enhances]), complemento(['CRMP-2', expression, in, 'TGW', human, neuroblastoma, cells, via, activation, of, 'RET', receptor, tyrosine, kinase])]). relacion([sujeto(['GDNF-mediated', 'CRMP-2', expression, was]), verbo([regulated]), complemento([mainly, by, the, extracellular, regulated, kinase, '(', 'ERK)', 'pathway,', but, was, independent, of, activation, of, phosphatidylinositol, 3, -, kinase, and, 'Src', family, kinases])]). relacion([sujeto(['The', 'SP1,', 'E2F,', and, 'GATA1/2']), verbo([binding]), complemento([sites, appeared, to, play, some, roles, in, regulation, of, 'CRMP-2', expression])]). relacion([sujeto(['However,', neuritogenesis, of, 'TGW', cells, was, mostly, dependent, on, 'Src', family, kinase, activity, and, not, 'ERK', 'activity,', indicating, that, the]), verbo([increased]), complemento([expression, of, 'CRMP-2', alone, was, not, sufficient, for, neuritogenesis])]). relacion([sujeto(['Recent', studies]), verbo([have]), complemento([revealed, that, acquired, alterations, in, genes, that, regulate, normal, haematopoiesis, are, frequently, detected, in, leukaemia])]). relacion([sujeto(['The', progression, to, leukaemia, depends, on, additional, mutations, that]), verbo([promote]), complemento([the, survival, of, developmentally, arrested, cells])]). relacion([sujeto(['The', cell]), verbo([nuclear]), complemento([proteins, were, extracted, and, analyzed, by, 'Western', blot, with, antibodies, against, 'GATA-1,', 'GATA-2'])]). relacion([sujeto(['Electrophoretic', mobility, shift, assay, '(', 'EMSA)', and, antibody, gel, supershift, assay, was, performed, using, '(', 32, ')', 'P', labeled, 'GATA', consensus, oligonucleotide, which, contains]), verbo([binding]), complemento([site, for, 'GATA', transcription, factors])]). relacion([sujeto(['PNS', could]), verbo([promote]), complemento([the, proliferation, of, 'CFU-GM', and, 'CFU-E', and, induce, the, expression, of, 'GATA-1,', 'GATA-2'])]). relacion([sujeto(['The']), verbo([nuclear]), complemento([proteins, of, both, 'GATA-1', and, 'GATA-2', in, 'K562,', 'CHRF-288', and, 'Meg-01', cells, treated, by, 'PNS', were, increased, by, '(', 1.5, -, 2.8, ')', and, '(', 2.0, -, 3.1, ')', -, fold, over, untreated, cells, respectively])]). relacion([sujeto(['GATA']), verbo([binding]), complemento([activity, initiated, by, 'PNS', was, apparently, elevated, to, form, higher, density, band, of, 'GATA-DNA', complex])]). relacion([sujeto(['The', predominant, 'GATA']), verbo([binding]), complemento([complex, was, mainly, attributable, to, both, 'GATA-1', and, 'GATA-2', proteins, being, in, phosphorylated, status])]). relacion([sujeto(['PNS', can]), verbo([induce]), complemento([the, synthesis, of, transcription, factors, 'GATA-1', and, 'GATA-2', and, enhance, their, 'DNA', binding, 'activity,', which, could, play, a, role, in, the, 'up-regulation', of, the, expression, genes, related, to, proliferation, and, differentiation, in, hematopoietic, cells])]). relacion([sujeto(['The', 'TMD', and, 'AMKL', blasts, are, morphologically, and, 'immuno-phenotypically', 'identical,', and]), verbo([have]), complemento([the, same, acquired, mutations, in, 'GATA1'])]). relacion([sujeto(['Among', the, significant, 'differences,', 'CDKN2C,', the, effector, of, 'GATA1-mediated', cell, cycle, 'arrest,', was]), verbo([increased]), complemento([in, 'AMKL', but, not, 'TMD,', despite, the, similar, level, of, 'GATA1'])]). relacion([sujeto(['In', 'contrast,', 'MYCN', '(', 'neuroblastoma-derived', 'oncogene)', was]), verbo([expressed]), complemento([in, 'TMD', at, a, significantly, greater, level, than, in, 'AMKL'])]). relacion([sujeto(['MYCN']), verbo([has]), complemento([not, previously, been, described, in, leukaemogenesis])]). relacion([sujeto(['This', study]), verbo([provides]), complemento([markers, discriminating, 'TMD', from, 'AMKL-M7', in, 'DS'])]). relacion([sujeto(['These', markers]), verbo([have]), complemento([the, potential, as, 'predictive,', diagnostic, and, therapeutic, targets])]). relacion([sujeto(['In', 'addition,', the, study]), verbo([provides]), complemento([further, clues, into, the, pathomechanisms, discerning, 'self-regressive', from, the, progressive, phenotype])]). relacion([sujeto(['We']), verbo([have]), complemento([proposed, a, 'model,', whereby, a, signal, generated, by, 'wild-type', cells, '(', red, cell, differentiation, 'signal;', 'REDS)', overcomes, the, intrinsic, defect, in, 'Gata1-overexpressing', erythroid, cells])]). relacion([sujeto(['To', substantiate, this, 'notion,', we]), verbo([have]), complemento([exploited, a, tissue, specific, 'Cre/loxP', system, and, the, process, of, 'X-inactivation', to, generate, mice, that, overexpress, 'Gata1', in, half, the, erythroid, cells, and, are, 'Gata1', null, in, the, other, half])]). relacion([sujeto(['This', study, demonstrates, the, importance, of, intercellular, signalling, in]), verbo([regulating]), complemento(['Gata1', activity, and, that, this, homotypic, signalling, between, erythroid, cells, is, crucial, to, normal, differentiation])]). relacion([sujeto(['The', activity, of, transcription, factors, is, tightly]), verbo([modulated]), complemento([by, posttranslational, modifications, affecting, 'stability,', 'localization,', and, 'protein-protein', interactions])]). relacion([sujeto(['Conjugation', to, 'SUMO', is, a, reversible, posttranslational, modification, that]), verbo([has]), complemento([been, shown, to, regulate, important, transcription, factors, involved, in, cell, 'proliferation,', 'differentiation,', and, tumor, suppression])]). relacion([sujeto(['Here,', we, demonstrate, that, the, erythroid, transcription, factor, 'GATA-1', is, sumoylated, in, vitro, and, in, vivo, and, map, the, single, lysine, residue]), verbo([involved]), complemento([in, 'SUMO-1', attachment])]). relacion([sujeto(['We', show, that, the]), verbo([nuclear]), complemento(['RING', finger, protein, 'PIASy', promotes, sumoylation, of, 'GATA-1', and, dramatically, represses, its, transcriptional, activity])]). relacion([sujeto(['We', present, evidence, that, a, nonsumoylatable, 'GATA-1', mutant, is, indistinguishable, from, the, 'WT', protein, in, its, ability, to, transactivate, a, reporter, gene, in, mammalian, cells, and, in, its, ability, to]), verbo([trigger]), complemento([endogenous, globin, expression, in, 'Xenopus', explants])]). relacion([sujeto(['Gene-targeting', experiments, in, transgenic, mice]), verbo([have]), complemento([revealed, an, essential, role, for, 'GATA-1', in, the, normal, differentiation, and, development, of, erythroid, cells])]). relacion([sujeto(['GATA-1', is]), verbo([phosphorylated]), complemento([in, vivo, on, seven, of, its, serine, 'residues;', the, regulation, and, function, of, 'GATA-1', 'phosphorylation,', 'however,', is, not, understood])]). relacion([sujeto(['We', show, that, 'EGF-induced', 'MAPK', signalling, results, in, the, phosphorylation, of, ectopically]), verbo([expressed]), complemento(['GATA-1', in, 'COS', cells])]). relacion([sujeto(['This', phosphorylation, can, be, positively, or, negatively]), verbo([regulated]), complemento([by, genetic, manipulation, of, the, 'MAPK', pathway, through, expression, of, constitutively, 'activated,', or, 'dominant-negative,', mutants, of, 'MAPK', kinase, '(', 'MAPKK),', an, upstream, regulator, of, 'MAPK', activity])]). relacion([sujeto(['In', vitro, phosphorylation, experiments, using, purified, 'MAPK', and, either, recombinant, 'GATA-1', or, synthetic, 'GATA-1', peptides]), verbo([suggest]), complemento([that, 'GATA-1', is, a, 'MAPK', substrate, with, 'MAPK', phosphorylation, occurring, primarily, on, 'Ser26', and, 'Ser178'])]). relacion([sujeto(['We', also, show, that, 'GATA-1', is]), verbo([phosphorylated]), complemento([in, 'factor-dependent', haemopoietic, progenitor, cells, in, response, to, 'cytokine-induced', signalling])]). relacion([sujeto(['Finally,', we, demonstrate, that, mutation, of, serines, 26, and, 178, compromises, the, ability, of, 'GATA-1', to]), verbo([interact]), complemento([with, the, 'LIM-only', protein, 'LMO2', when, both, proteins, are, expressed, in, 'COS', cells])]). relacion([sujeto(['Chronic', myelogenous, leukemia, '(', 'CML)', results, from, a, 't(9,22)', 'translocation,', producing, the, 'p210(BCR-ABL)', 'oncoprotein,', a, tyrosine, kinase, that]), verbo([causes]), complemento([transformation, and, chemotherapy, resistance])]). relacion([sujeto(['To', further, understand, mechanisms]), verbo([mediating]), complemento([chemotherapy, 'resistance,', we, identified, 556, differentially, regulated, genes, in, 'HL-60', cells, stably, expressing, 'p210(BCR-ABL)', versus, those, expressing, an, empty, vector, using, cDNA, 'macro-', and, oligonucleotide, microarrays])]). relacion([sujeto(['In', 'HL-60/BCR-ABL', and, 'K562', cells, '(']), verbo([expressing]), complemento(['p210(BCR-ABL)),', abundant, cytoplasmic, 'Hsp70', expression, was, detected, by, immunoblot, analysis])]). relacion([sujeto(['Moreover,', cells, isolated, from, bone, marrow, aspirates, of, patients, in, different, stages, of, 'CML', '(', 'chronic,', 'aggressive,', and, blast, 'crisis)']), verbo([express]), complemento(['Hsp70'])]). relacion([sujeto(['Expression', of, 'p210(BCR-ABL)', in, 'BCR-ABL', negative, cells]), verbo([induced]), complemento([transcription, of, the, proximal, 'Hsp70', promoter])]). relacion([sujeto(['Mutational', analysis, mapped, the, major, 'p210(BCR-ABL)', responsive, element, to, a, high, affinity, 5, '\'', '(', 'A/T)GATA(A/G)-3\'', &, 'quot;GATA"', response, element, '(', 'GATA-RE)', that]), verbo([binds]), complemento(['GATA-1', in, 'CML', cells])]). relacion([sujeto(['The', 'GATA-RE', was, sufficient, to]), verbo([confer]), complemento(['p210(BCR-ABL)-', and, 'p185(BCR-ABL)-mediated', 'trans-activation', to, an, inert, promoter])]). relacion([sujeto(['Short', interfering, 'RNA']), verbo([mediated]), complemento([&, 'quot;knockdown"', of, 'Hsp70', expression, in, 'K562', cells, induced, marked, sensitivity, to, 'paclitaxel-induced', apoptosis])]). relacion([sujeto(['Together', these, findings, indicate, that, 'BCR-ABL']), verbo([confers]), complemento([chemotherapeutic, resistance, through, intracellular, signaling, to, the, 'GATA-RE', element, found, in, the, promoter, region, of, the, 'anti-apoptotic', 'Hsp70', protein])]). relacion([sujeto(['We']), verbo([suggest]), complemento([that, 'down-regulation', of, the, 'GATA-Hsp70', pathway, may, be, useful, in, the, treatment, of, 'chemotherapy-resistant', 'CML'])]). relacion([sujeto(['Patients', with, 3, q21q26, rearrangements, seem, to, share, similar, clinicopathologic, features, and, a, common, molecular, 'mechanism,']), verbo([leading]), complemento([to, myelodysplasia, or, acute, myeloid, leukemia, '(', 'AML)'])]). relacion([sujeto(['The', ectopic, expression, of, 'EVI1', '(', 3, 'q26)']), verbo([has]), complemento([been, implicated, in, the, dysplasia, that, characterizes, this, subset, of, myeloid, neoplasias])]). relacion([sujeto(['However,', lack, of, 'EVI1', expression]), verbo([has]), complemento([been, reported, in, several, 'cases,', and, overexpression, of, 'EVI1', was, detected, in, 9, '%', of, 'AML', cases, without, 3, q26, abnormalities])]). relacion([sujeto(['We']), verbo([report]), complemento([the, molecular, characterization, of, seven, patients, with, 'inv(3)(q21q26),', 't(3;3)(q21;q26)', or, related, abnormalities])]). relacion([sujeto(['GATA2', '(', 3, 'q21)', was]), verbo([found]), complemento([to, be, overexpressed, in, 5, of, the, 7, patients])]). relacion([sujeto(['GATA2', is, highly]), verbo([expressed]), complemento([in, stem, 'cells,', and, its, expression, dramatically, decreases, when, erythroid, and, megakaryocytic, differentiation, proceeds])]). relacion([sujeto(['No', mutations, in, 'GATA1', were]), verbo([found]), complemento([in, any, 'patient,', excluding, loss, of, function, of, 'GATA1', as, the, cause, of, 'GATA2', overexpression])]). relacion([sujeto(['We']), verbo([report]), complemento([finding, molecular, heterogeneity, in, patients, with, 3, q21q26, rearrangements, in, both, breakpoints, and, in, the, expression, pattern, of, the, genes, near, these, breakpoints])]). relacion([sujeto(['Our', data]), verbo([suggest]), complemento([that, a, unique, mechanism, is, not, likely, to, be, involved, in, 3, q21q26, rearrangements])]). relacion([sujeto(['Mutations', in, the, 'GATA-1', gene]), verbo([have]), complemento([been, identified, in, patients, with, familial, macrothrombocytopenia, and, 'Down\'s', syndrome, patients, with, a, transient, myeloproliferative, disorder, 'and/or', acute, megakaryoblastic, leukemia])]). relacion([sujeto(['We']), verbo([found]), complemento([that, 'GATA-1', strongly, activates, transcription, of, the, 'Tac-2', 'gene,', which, encodes, 'proneurokinin-B,', a, precursor, of, 'neurokinin-B', '(', 'NK-B)'])]). relacion([sujeto(['Neurokinins', function, through, 'G', 'protein-coupled', transmembrane, receptors, to]), verbo([mediate]), complemento([diverse, physiological, responses, including, pain, perception, and, the, control, of, vascular, tone])]). relacion([sujeto(['Tac-2', was]), verbo([expressed]), complemento([in, normal, murine, erythroid, cells, and, was, induced, upon, ex, vivo, erythropoiesis])]). relacion([sujeto(['An', estrogen, receptor, fusion, to, 'GATA-1', '(', 'ER-GATA-1)', and, endogenous, 'GATA-1', both, occupied, a, region, of, 'Tac-2', 'intron-7,', which, contains, two]), verbo([conserved]), complemento(['GATA', motifs])]). relacion([sujeto(['Genetic', complementation, analysis, in, 'GATA-1-null', 'G1E', cells, revealed, that, endogenous, 'GATA-2', occupied, the, same, region, of, 'intron-7,', and, expression, of, 'ER-GATA-1', displaced, 'GATA-2', and]), verbo([activated]), complemento(['Tac-2', transcription])]). relacion([sujeto(['Erythroid', cells, did, not]), verbo([express]), complemento([neurokinin, 'receptors,', whereas, aortic, and, yolk, sac, endothelial, cells, differentially, expressed, neurokinin, receptor, subtypes])]). relacion([sujeto(['Since', 'NK-B']), verbo([induced]), complemento([cAMP, accumulation, in, yolk, sac, endothelial, 'cells,', these, results, suggest, a, new, mode, of, vascular, regulation, in, which, 'GATA-1', controls, 'NK-B', synthesis, in, erythroid, cells])]). relacion([sujeto(['These', transcription, factors, influence, the, expression, of, their, own]), verbo([target]), complemento(['genes,', leading, to, megakaryocyte, maturation, and, platelet, release])]). relacion([sujeto(['Families', with, hereditary, thrombocytopenia]), verbo([have]), complemento([been, described, due, to, mutations, in, the, 'GATA1', 'gene,', and, target, genes, were, studied])]). relacion([sujeto(['The', final]), verbo([release]), complemento([of, platelets, from, the, megakaryocyte, is, strongly, dependent, on, the, formation, of, 'so-called', proplatelets])]). relacion([sujeto(['The', formation, of, pseudopodia]), verbo([requires]), complemento([the, presence, of, microtubuli])]). relacion([sujeto(['Bone', marrow, '(', 'BM)', 'SP', cells, uniformly]), verbo([express]), complemento([the, 'pan-hematopoietic', marker, 'CD45,', whereas, tissue, 'SP', cells, are, heterogeneous, in, 'CD45', expression])]). relacion([sujeto(['In', previous, 'studies,', we]), verbo([found]), complemento([that, 'CD45', is, expressed, on, 75, '%', of, lung, 'SP', cells])]). relacion([sujeto(['By', immunostaining, for, 'alpha-smooth', muscle, actin, and, 'cytokeratin,', we]), verbo([found]), complemento([significant, differences, in, the, relative, expression, patterns, of, these, markers, in, lung, and, marrow, 'SP', cell, subtypes])]). relacion([sujeto(['However,', little, is, known, regarding, the, mechanisms, that]), verbo([modulate]), complemento([their, interaction, within, cells])]). relacion([sujeto(['In', the, present, 'study,', we]), verbo([have]), complemento([identified, 'TACC3', as, a, 'FOG-1-interacting', protein])]). relacion([sujeto(['Transforming', acidic, 'coiled-coil', protein, 3, '(', 'TACC3),', a, protein, that, is, highly]), verbo([expressed]), complemento([in, hematopoietic, 'cells,', has, been, reported, to, have, a, critical, role, in, the, expansion, of, immature, hematopoietic, progenitors])]). relacion([sujeto(['We', show, that, 'TACC3', affects, 'FOG-1']), verbo([nuclear]), complemento(['localization,', altering, the, interaction, between, 'GATA-1', and, 'FOG-1'])]). relacion([sujeto(['We', observe, that, high, levels, of, 'TACC3']), verbo([inhibit]), complemento([the, function, of, 'FOG-1', as, a, transcriptional, cofactor, of, 'GATA-1'])]). relacion([sujeto(['Furthermore,', forced, expression, of, 'TACC3', to, levels, similar, to, those]), verbo([found]), complemento([in, progenitor, cells, delays, terminal, maturation, of, 'MEL', and, 'G1ER', 'cells,', two, cell, models, of, erythroid, cell, development])]). relacion([sujeto(['We']), verbo([suggest]), complemento([a, role, for, 'TACC3', in, regulating, the, cellular, distribution, of, 'FOG-1', and, thus, the, direct, interaction, of, 'GATA-1', and, 'FOG-1', as, a, mechanism, to, control, the, transition, between, expansion, of, multipotential, progenitor, cell, populations, and, final, stages, of, erythroid, maturation])]). relacion([sujeto(['Expression', of, the, myeloid, transcription, factor, 'GATA1', is]), verbo([required]), complemento([for, early, stages, of, eosinophil, differentiation])]). relacion([sujeto(['Defining', mechanisms]), verbo([regulating]), complemento([eosinophil, 'GATA1', expression, will, be, important, to, understand, development, of, this, lineage])]). relacion([sujeto(['However,', the, 'cis-elements']), verbo([required]), complemento([for, eosinophil, 'GATA1', expression, are, not, fully, characterized])]). relacion([sujeto(['In', 'eosinophils,', 'GATA1', and, 'CCAAT/enhancer']), verbo([binding]), complemento([protein, epsilon, '(', 'C/EBP', 'epsilon)', do, not, bind, 'HS', 1, but, bind, selectively, a, 'cis-element', in, the, first, 'GATA1', intron])]). relacion([sujeto(['Thus,', 'HS', 1, is, not]), verbo([required]), complemento([for, eosinophil, 'GATA1', expression])]). relacion([sujeto(['Instead,', this, study]), verbo([suggests]), complemento([a, previously, unsuspected, role, for, the, 'GATA1', intron, element, for, this, function])]). relacion([sujeto(['Mice', deficient, in, 'GATA-1', or, 'NF-E2']), verbo([have]), complemento([a, 200, -, 300, '%', increase, in, bone, volume, and, formation, parameters])]). relacion([sujeto(['Osteoblast', proliferation]), verbo([increased]), complemento([up, to, 6, -, fold, when, cultured, with, megakaryocytes])]). relacion([sujeto(['A', 'megakaryocyte-osteoblast', interaction, plays, a, role, in, the]), verbo([increased]), complemento([bone, formation, in, these, mice])]). relacion([sujeto(['GATA-1', and, 'NF-E2', are, transcription, factors]), verbo([required]), complemento([for, the, differentiation, of, megakaryocytes])]). relacion([sujeto(['Mice', deficient, in, these, factors]), verbo([have]), complemento([phenotypes, characterized, by, markedly, increased, numbers, of, immature, 'megakaryocytes,', a, concomitant, drastic, reduction, of, 'platelets,', and, a, striking, increased, bone, mass])]). relacion([sujeto(['The', similar, bone, phenotype, in, both, animal, models]), verbo([led]), complemento([us, to, explore, the, interaction, between, osteoblasts, and, megakaryocytes])]). relacion([sujeto(['A', marked, 2, -, to, 3, -, fold]), verbo([increase]), complemento([in, trabecular, bone, volume, and, bone, formation, indices, were, observed, in, these, mice])]). relacion([sujeto(['A', 20, -, to, 150, -, fold]), verbo([increase]), complemento([in, trabecular, bone, volume, was, measured, for, the, entire, femoral, medullary, canal])]). relacion([sujeto(['The']), verbo([increased]), complemento([bone, mass, phenotype, in, these, animals, was, not, caused, by, osteoclast, 'defects,', because, osteoclast, number, and, function, were, not, compromised, in, vitro, or, in, vivo])]). relacion([sujeto(['When', wildtype, or, mutant, osteoblasts, were, cultured, with, megakaryocytes, from, 'GATA-1-', or, 'NF-E2-deficient', 'mice,', osteoblast, proliferation]), verbo([increased]), complemento([over, 3, -, to, 6, -, fold, by, a, mechanism, that, required, 'cell-to-cell', contact])]). relacion([sujeto(['These', observations, show, an, interaction, between, megakaryocytes, and, 'osteoblasts,', which, results, in, osteoblast, proliferation, and]), verbo([increased]), complemento([bone, 'mass,', and, may, represent, heretofore, unrecognized, anabolic, pathways, in, bone])]). relacion([sujeto(['The', mechanism, of, 'IL-1beta', on, thrombocytosis, and, megakaryocytopoiesis]), verbo([has]), complemento([remained, controversial])]). relacion([sujeto(['In', previous, 'reports,', we]), verbo([have]), complemento([demonstrated, the, expression, of, 'IL-1', receptors, '(', 'IL-1RI', and, 'IL-1RII)', and, enhancing, effects, of, 'IL-1beta', on, primary, human, megakaryocytic, '(', 'MK)', cells])]). relacion([sujeto(['In', this, 'study,', we, investigated, the, possible, direct, effects, of, 'IL-1beta', on, the, expression, of, thrombopoietin, '(', 'TPO)', and, transcription, factors, 'c-Jun,', 'c-Fos,', 'GATA-1,', and, p45]), verbo([nuclear]), complemento(['factor-E2', '(', 'NF-E2)', in, 'MK', cell, lines, 'CHRF', and, 'Meg-01'])]). relacion([sujeto(['In', 'CHRF', 'cells,', 'mRNA:', 'c-Jun', '[', 3.4, -, 'fold,', peaked, at, 15, 'minutes],', 'c-Fos', '[', 4.2, -, 'fold,', 15, 'minutes],', 'GATA-1', '[', 4.0, -, 'fold,', 60, 'minutes],', 'NF-E2', '[', 3.2, -, 'fold,', 120, 'minutes]', and, protein, 'expression:', 'c-Jun', '[', 3.0, -, 'fold,', 30, 'minutes],', 'c-Fos', '[', 1.7, -, 'fold,', 30, 'minutes],', 'GATA-1', '[', 11.5, -, 'fold,', 60, 'minutes],', 'NF-E2', '[', 12.5, -, 'fold,', 120, 'minutes]', were, evidently]), verbo([enhanced]), complemento([after, treatment, with, 'IL-1beta'])]). relacion([sujeto(['The', response, to, 'IL-1beta', was, consistent, in, the, total, cell, and]), verbo([nuclear]), complemento([extracts, and, was, significantly, reduced, by, pretreatment, with, actinomycin, 'D', or, cycloheximide])]). relacion([sujeto(['An', 'IL-1-receptor', antagonist, '(', 'IL-1RA)']), verbo([inhibited]), complemento([the, stimulatory, effects, of, 'IL-1beta', on, these, transcription, factors, by, as, much, as, 78, '%'])]). relacion([sujeto(['TPO', expression, was]), verbo([increased]), complemento([by, more, than, 9.9, -, fold, on, stimulation, with, 'IL-1beta'])]). relacion([sujeto(['The', mechanism, might, be]), verbo([mediated]), complemento([by, 'IL-1beta', receptors, and, require, transcription, or, protein, synthesis])]). relacion([sujeto(['The', direct, involvement, of, 'IL-1beta', in, the, 'MK', lineage, may]), verbo([provide]), complemento([an, explanation, for, the, phenomenon, of, thrombocytosis, during, inflammatory, responses])]). relacion([sujeto(['During', erythroid, differentiation]), verbo([induced]), complemento([by, butyric, acid, '(', 'BA)', or, 'hemin,', chebulinic, acid, not, only, inhibited, the, hemoglobin, synthesis, of, 'BA-', and, 'hemin-treated', 'K562', cells, in, 'concentration-dependent', manner, with, 'IC50', of, 4, 'micromol/L', and, 40, 'micromol/L', 'respectively,', but, also, inhibited, another, erythroid, differentiation, marker, acetylcholinesterase, at, the, concentration, of, 50, 'micromol/L', in, the, cells, either, treated, or, untreated, with, each, erythroid, differentiation, 'inducers,', whereas, chebulinic, acid, 50, 'micromol/L', did, not, change, 'GPA', protein, expression, in, these, cells, significantly])]). relacion([sujeto(['When', 'K562', cells, were, treated, with, 'TPA', 50, 'microg/L', for, 72, h, to]), verbo([induce]), complemento([megakaryocytic, 'differentiation,', the, presence, of, chebulinic, acid, 50, 'micromol/L', slightly, provoked, the, decrease, of, 'GPA', protein, expression, induced, by, 'TPA'])]). relacion([sujeto(['Chebulinic', acid, had, inhibitory, effect, on, erythroid, differentiation, likely, through, changing, transcriptional, activation, of, differentiation, relative, 'genes,', which]), verbo([suggests]), complemento([that, chebulinic, acid, or, other, tannins, might, influence, the, efficiency, of, some, 'anti-tumor', 'drugs-induced', differentiation, or, the, hematopoiesis, processes])]). relacion([sujeto(['Paclitaxel', '(', 'Px)', is, a, cancer, chemotherapeutic, agent, that]), verbo([causes]), complemento([bone, marrow, '(', 'BM)', cytotoxicity, by, microtubule, stabilization, and, by, modifications, in, the, expression, of, several, genes])]). relacion([sujeto(['Apoptosis', '(', 24, +, /, -, 0.81, '%', ',', 'P', &, 'lt;', 0.01, ')', ',', inhibition, of, colony, growth, '(', 'burst-forming', 'units-erythroid', '[', 'BFU-E]', and, 'granulocyte-erythroid-macrophage', '[', 'GEM]),', and]), verbo([decrease]), complemento([in, 'BM', cellularities, '(', 28, +, /, -, 4.2, '%', of, 'control)', were, maximal, at, 24, h, following, 'Px'])]). relacion([sujeto(['Thus,', cells, that, survive, injury, seem, to, be]), verbo([stimulated]), complemento([to, produce, early, '(', 24, -, 48, 'h)', 'erythroid-related', and, antiapoptotic, proteins])]). relacion([sujeto(['Therefore,', the, results]), verbo([suggest]), complemento([an, in, vivo, interplay, between, specific, transcription, factors, and, 'Bcl-x(L)', during, progenitor, cell, survival, and, 'proliferation;', mechanisms, triggered, to, restore, size, and, composition, of, the, erythroid, compartment])]). relacion([sujeto(['Here', we, identify, the, erythroid, 'cell-specific', glycophorin, 'A', gene, '(', 'GPA)', as, a]), verbo([target]), complemento([of, 'SCL', in, primary, hematopoietic, cells, and, show, that, 'SCL', occupies, the, 'GPA', locus, in, vivo])]). relacion([sujeto(['In', 'addition,', our, observations]), verbo([suggest]), complemento([functional, specialization, within, this, 'complex,', as, 'SCL', provides, its, 'HLH', protein, interaction, 'motif,', 'GATA-1', exerts, a, 'DNA-tethering', function, through, its, binding, to, a, critical, 'GATA', element, in, the, 'GPA', 'promoter,', and, 'E47', requires, its, 'N-terminal', moiety, '(', most, likely, entailing, a, transactivation, 'function)'])]). relacion([sujeto(['Together,', these, observations]), verbo([reveal]), complemento([the, functional, complementarities, of, transcription, factors, within, the, 'SCL', complex, and, the, essential, role, of, 'SCL', as, a, nucleation, factor, within, a, 'higher-order', complex, required, to, activate, gene, 'GPA', expression])]). relacion([sujeto(['Overexpression', of, 'CDA', in, 'non-DS', 'THP-1', cells, was]), verbo([associated]), complemento([with, a, 100, -, fold, decreased, 'ara-C', sensitivity, and, 40, -, fold, decreased, 'ara-CTP', generation])]). relacion([sujeto(['The', presence, of, several, 'GATA1']), verbo([binding]), complemento([sites, in, the, 'CDAsf', promoter, and, the, uniform, detection, of, 'GATA1', mutations, in, 'DS', megakaryocytic, leukemia, suggested, the, potential, role, of, 'GATA1', in, regulating, 'CDA', transcription, and, the, 'CDAsf', promoter, acting, as, an, enhancer])]). relacion([sujeto(['Transfection', of, 'GATA1', into, 'Drosophila', 'Mel-2', cells]), verbo([stimulated]), complemento([the, 'CDAlf', promoter, in, a, 'dose-dependent', fashion])]). relacion([sujeto(['Additional', identification, of, the, mechanisms, of, differential, expression, of, genes, encoding, enzymes]), verbo([involved]), complemento([in, 'ara-C', metabolism, between, 'DS', and, 'non-DS', myeloblasts, may, lead, to, improvements, in, 'AML', therapy])]). relacion([sujeto(['These', observations, indicate, that, during, embryonic, 'development,', different, thresholds, of, 'VEGF', are]), verbo([required]), complemento([for, the, migration, and, clonal, expansion, of, hematopoietic, precursors])]). relacion([sujeto(['Strikingly,', 'gain-of-function', of, 'SCL', partially, complements, the, hematopoietic, defect]), verbo([caused]), complemento([by, the, hypomorph, 'Vegf(lo)', 'allele,', and, 're-establishes', the, survival, of, erythroid, cells, and, the, expression, of, erythroid, genes, '(', 'Gata1', and, 'betaH1)'])]). relacion([sujeto(['This', indicates, that, 'SCL', functions, downstream, of, 'VEGF', to]), verbo([ensure]), complemento([an, expansion, of, the, hematopoietic, compartment])]). relacion([sujeto(['The', transcription, factor, 'GATA-1,', together, with, its, cofactor, 'FOG-1,']), verbo([regulates]), complemento([erythropoiesis, and, megakaryocytopoiesis])]). relacion([sujeto(['Mutations', in, the, 'DNA', or, 'FOG-1']), verbo([binding]), complemento([sites, of, its, 'N-terminal', zinc, finger, result, in, different, illnesses])]). relacion([sujeto(['Alterations', of, the, 'FOG-1', face, are, responsible, for, dyserythropoietic, anemia, with, thrombocytopenia, while, 'R216Q,', the, only, mutation, identified, in, the, 'DNA', 'face,']), verbo([induces]), complemento(['X-linked', thrombocytopenia, with, thalassemia, '(', 'XLTT)'])]). relacion([sujeto(['The', former, disorder]), verbo([has]), complemento([been, studied, in, detail, whereas, little, is, known, about, the, latter, since, only, one, family, has, been, investigated])]). relacion([sujeto(['However,', a, thalassemia, minor, phenotype]), verbo([has]), complemento([only, been, described, in, patients, with, 'XLTT', whereas, severe, anemia, and, thrombocytopenia, with, evident, defects, of, platelet, composition, and, function, may, be, observed, only, in, dyserythropoietic, anemia, with, thrombocytopenia])]). relacion([sujeto(['The', transcription, factor, 'GATA-1', plays, a, significant, role, in, erythroid, differentiation, and, association, with, 'CBP']), verbo([stimulates]), complemento([its, activity, by, acetylation])]). relacion([sujeto(['In', the, present, 'study,', we, investigated, whether, class, 'I', and, class, 'II', 'HDACs']), verbo([interact]), complemento([with, 'GATA-1', to, regulate, its, function, and, 'indeed,', 'GATA-1', is, directly, associated, with, 'HDAC3,', 'HDAC4', and, 'HDAC5'])]). relacion([sujeto(['The', expression, profiling, and, our, previous, observation, that, 'GATA-2']), verbo([interacts]), complemento([with, members, of, the, 'HDAC', family, prompted, us, to, investigate, further, the, biological, relevance, of, the, interaction, between, 'GATA-1', and, 'HDAC5'])]). relacion([sujeto(['Coexpression', of, 'HDAC5']), verbo([suppressed]), complemento([the, transcriptional, potential, of, 'GATA-1'])]). relacion([sujeto(['Furthermore,', a, portion, of, 'HDAC5', moved, to, the, cytoplasm, concomitant, with, 'MEL', cell, erythroid, 'differentiation,', which, was]), verbo([induced]), complemento([by, treatment, with, 'N,N\'-hexamethylenebisacetamide'])]). relacion([sujeto(['These', observations, support, the, suggestion, that, control, of, the, 'HDAC5', nucleocytoplasmic, distribution, might, be]), verbo([associated]), complemento([with, 'MEL', cell, 'differentiation,', possibly, through, regulated, 'GATA-1', transactivation])]). relacion([sujeto(['Members', of, the, 'GATA', and, 'RUNX', families, of, genes, appear, to]), verbo([have]), complemento([conserved, functions, during, hematopoiesis, from, 'Drosophila', to, mammals])]). relacion([sujeto(['In', 'Drosophila,', the, 'GATA', factor, 'Serpent', '(', 'Srp)', is]), verbo([required]), complemento([in, blood, cell, progenitors, for, the, formation, of, the, two, populations, of, blood, cells, '(', plasmatocytes, and, crystal, 'cells),', while, the, 'RUNX', factor, 'Lozenge', '(', 'Lz)', is, specifically, required, for, crystal, cell, development])]). relacion([sujeto(['Our', results, indicate, that, 'Lz', can]), verbo([trigger]), complemento([crystal, cell, development])]). relacion([sujeto(['Interestingly,', we, show, that, 'Lz', function, is, strictly, dependent, on, the, presence, of, functional, 'Srp', and, that, 'Srp', and, 'Lz', cooperate, to]), verbo([induce]), complemento([crystal, cell, differentiation, in, vivo])]). relacion([sujeto(['Furthermore,', we, show, that, 'Srp', and, 'Lz', directly]), verbo([interact]), complemento([in, vitro, and, that, this, interaction, is, conserved, between, 'Drosophila', and, mammals])]). relacion([sujeto(['Moreover,', both, 'Srp', and, mouse, 'GATA1', synergize, with, mouse, 'RUNX1', to]), verbo([activate]), complemento([transcription])]). relacion([sujeto(['We', propose, that, interaction, and, cooperation, between, 'GATA', and, 'RUNX', factors, may, play, an, important, role, in]), verbo([regulating]), complemento([blood, cell, formation, from, 'Drosophila', to, mammals])]). relacion([sujeto(['To', assess, functions, of, 'GATA-1-FOG-1', association, during, mouse, 'development,', we, used, the, 'GATA-1', hematopoietic, regulatory, domain, to, generate, transgenic, mouse, lines]), verbo([expressing]), complemento([a, mutant, 'GATA-1,', which, contains, a, substitution, of, glycine, 205, for, valine, '(', 'V205G)', that, abrogates, its, association, with, 'FOG-1'])]). relacion([sujeto(['In', 'high-expressor', lines, we, observed, that, the, 'GATA-1(V205G)', rescues, 'GATA-1-deficient', mice, from, embryonic, lethality, at, the, expected, 'frequency,']), verbo([revealed]), complemento([that, excess, 'GATA-1(V205G)', can, eliminate, the, lethal, anemia, that, is, due, to, 'GATA-1', deficiency])]). relacion([sujeto(['Our', findings]), verbo([reveal]), complemento([an, indispensable, role, for, the, association, of, 'GATA-1', and, 'FOG-1', during, 'late-stage', megakaryopoiesis, and, provide, a, unique, model, for, 'X-linked', thrombocytopenia, with, inherited, 'GATA-1', mutation])]). relacion([sujeto(['Acquired', mutations, in, megakaryocyte, transcription, factor, 'GATA1']), verbo([have]), complemento([recently, been, reported, in, 'Down', syndrome, '(', 'DS),', transient, myeloproliferative, disorder, '(', 'TMD),', and, acute, megakaryoblastic, leukemia, '(', 'AMKL)'])]). relacion([sujeto(['To']), verbo([provide]), complemento([novel, insight, into, 'GATA1', mutations, in, 'DS,', genomic, 'DNA', was, assayed, from, 12, 'AMKL', and, 4, 'TMD', cases, '(', including, 'neonatal,', prediagnosis, samples, in, 4, of, 16, ')', ',', neonatal, blood, spots, from, 21, 'DS', children, without, clinically, evident, 'TMD', or, 'AMKL,', and, 62, 'non-DS', cord, blood, 'samples,', using, techniques, not, previously, employed, with, such, samples])]). relacion([sujeto(['They', were, present, at, birth, in, 2, of, 21, 'DS', 'neonates,', who]), verbo([have]), complemento([not, 'yet,', but, could, 'still,', develop, 'AMKL', '(', now, 26, and, 31, 'months)'])]). relacion([sujeto(['The', findings]), verbo([have]), complemento([implications, for, pathogenesis, of, 'DS', 'TMD', and, 'AMKL', and, highlight, parallels, between, 'DS', 'AMKL', and, other, childhood, leukemias])]). relacion([sujeto(['The', early, genetic, 'pathway(s)']), verbo([triggering]), complemento([the, pathogenesis, of, coronary, artery, disease, '(', 'CAD)', and, myocardial, infarction, '(', 'MI)', remain, largely, unknown])]). relacion([sujeto(['Here,', we, describe, an, autosomal, dominant, form, of, 'CAD/MI', '(', 'adCAD1)', that, is]), verbo([caused]), complemento([by, the, deletion, of, seven, amino, acids, in, transcription, factor, 'MEF2A'])]). relacion([sujeto(['The', deletion, disrupts]), verbo([nuclear]), complemento([localization, of, 'MEF2A,', reduces, 'MEF2A-mediated', transcription, 'activation,', and, abolishes, synergistic, activation, by, 'MEF2A', and, by, the, transcription, factor, 'GATA-1', through, a, 'dominant-negative', mechanism])]). relacion([sujeto(['Mutations', in, transcription, factors, often, contribute, to, human, leukemias, by]), verbo([providing]), complemento([a, block, to, normal, differentiation])]). relacion([sujeto(['To', determine, whether, mutations, in, the, hematopoietic, transcription, factor, 'GATA1', are]), verbo([associated]), complemento([with, 'leukemia,', we, assayed, for, alterations, in, the, 'GATA1', gene, in, bone, marrow, samples, from, patients, with, various, subtypes, of, acute, leukemia])]). relacion([sujeto(['We', did, not]), verbo([find]), complemento([mutations, in, 'GATA1', in, leukemic, cells, of, 'DS', patients, with, other, types, of, acute, 'leukemia,', or, in, other, patients, with, 'AMKL', who, did, not, have, 'DS'])]). relacion([sujeto(['GATA', transcription, 'factors,', together, with, 'Friend', of, 'GATA', '(', 'FOG)', 'cofactors,', are]), verbo([required]), complemento([for, the, differentiation, of, diverse, cell, types])]). relacion([sujeto(['FOG-2', and, 'GATA-4', are]), verbo([required]), complemento([for, cardiac, development])]). relacion([sujeto(['Here', we]), verbo([have]), complemento([characterized, the, 'blood-forming', system, of, adult, zebrafish])]). relacion([sujeto(['These', results]), verbo([provide]), complemento([a, cellular, context, in, which, to, study, the, genetics, of, hematopoiesis])]). relacion([sujeto(['The', 'LIM', domain, protein, 'Lmo2', and, the, basic, 'helix-loop-helix', transcription, factor, 'Scl/Tal1', are]), verbo([expressed]), complemento([in, early, haematopoietic, and, endothelial, progenitors, and, interact, with, each, other, in, haematopoietic, cells])]). relacion([sujeto(['While', 'loss-of-function', studies]), verbo([have]), complemento([shown, that, 'Lmo2', and, 'Scl/Tal1', are, essential, for, haematopoiesis, and, angiogenic, remodelling, of, the, 'vasculature,', 'gain-of-function', studies, have, suggested, an, earlier, role, for, 'Scl/Tal1', in, the, specification, of, 'haemangioblasts,', putative, bipotential, precursors, of, blood, and, endothelium])]). relacion([sujeto(['In', zebrafish, 'embryos,', 'Scl/Tal1', can]), verbo([induce]), complemento([these, progenitors, from, early, mesoderm, mainly, at, the, expense, of, the, somitic, paraxial, mesoderm])]). relacion([sujeto(['We', show, that, this, restriction, to, the, somitic, paraxial, mesoderm, correlates, well, with, the, ability, of, 'Scl/Tal1', to]), verbo([induce]), complemento([ectopic, expression, of, its, interaction, partner, 'Lmo2'])]). relacion([sujeto(['Co-injection', of, lmo2, mRNA, with, 'scl/tal1', dramatically, extends, its, effect, to, 'head,', 'heart,', pronephros, and, pronephric, duct, mesoderm]), verbo([inducing]), complemento([early, blood, and, endothelial, genes, all, along, the, anteroposterior, axis])]). relacion([sujeto(['This', restriction, correlates, well, with, activation, of, gata1, transcription, and, 'co-injection', of, gata1, mRNA, along, with, 'scl/tal1', and, lmo2]), verbo([induces]), complemento([erythropoiesis, more, broadly, without, ventralising, or, posteriorising, the, embryo])]). relacion([sujeto(['While', no, ectopic, myeloid, development, from, the, 'Scl/Tal1-Lmo2-induced', haemangioblasts, was, 'observed,', a, dramatic]), verbo([increase]), complemento([in, the, number, of, endothelial, cells, was, found])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento(['that,', in, the, absence, of, inducers, of, erythroid, or, myeloid, 'haematopoiesis,', 'Scl/Tal1-Lmo2-induced', haemangioblasts, differentiate, into, endothelial, cells])]). relacion([sujeto(['Gata1', is, a, prototype, transcription, factor, that]), verbo([regulates]), complemento(['hematopoiesis,', yet, the, molecular, mechanisms, by, which, 'Gata1', transactivates, its, target, genes, in, vivo, remain, unclear])]). relacion([sujeto(['Of', the, tested, 'mutations,', replacement, of, six, lysine, residues, with, alanine, '(', 'Gata1KA6),', which]), verbo([inhibited]), complemento(['self-association', activity, of, 'Gata1,', reduced, the, 'Gata1-dependent', induction, of, reporter, gene, expression, driven, by, the, zebra, fish, gata1, hematopoietic, regulatory, domain, '(', gata1, 'HRD)'])]). relacion([sujeto(['Interestingly,', both, 'GATA', sites, in, the, double, 'GATA', motif, in, gata1, 'HRD', were, critical, for, the, promoter, activity, and, for]), verbo([binding]), complemento([of, the, 'self-associated', 'Gata1', 'complex,', whereas, only, the, 3, '\'', -, 'GATA', site, was, required, for, 'Gata1', monomer, binding])]). relacion([sujeto(['These', results, thus]), verbo([provide]), complemento([the, first, in, vivo, evidence, that, the, ability, of, 'Gata1', to, 'self-associate', critically, contributes, to, the, autoregulation, of, the, gata1, gene])]). relacion([sujeto(['Although', presumed, to]), verbo([regulate]), complemento(['transcription,', its, target, genes, are, largely, unknown])]). relacion([sujeto(['We', show, here, that, a]), verbo([nuclear]), complemento([complex, containing, 'TAL1,', its, 'DNA-binding', partner, 'E47,', zinc, finger, transcription, factor, 'GATA-1,', 'LIM', domain, protein, 'LMO2,', and, 'LIM', 'domain-binding', protein, 'Ldb1', transactivates, the, protein, 4.2, '(', 'P4'])]). relacion([sujeto(['Maximal', transcription, in, transiently, transfected, cells]), verbo([required]), complemento([both, 'E', box, 'GATA', elements, and, expression, of, all, five, components, of, the, complex])]). relacion([sujeto(['This', 'DNA-linking', activity]), verbo([required]), complemento(['Ldb1', and, increased, with, dimethyl, 'sulfoxide-induced', differentiation, of, murine, erythroleukemia, '(', 'MEL)', cells])]). relacion([sujeto(['In', 'contrast,', enforced, expression, in, 'MEL', cells, of, 'dimerization-defective', mutant, 'Ldb1,', as, well, as, 'wild-type', 'Ldb1,', significantly]), verbo([decreased]), complemento(['E', box, 'GATA', 'DNA-binding', 'activities,', 'P4'])]). relacion([sujeto(['These', studies, define, a, physiologic]), verbo([target]), complemento([for, a, 'TAL1-', and, 'GATA-1-containing', ternary, complex, and, reveal, a, positive, role, for, 'Ldb1', in, erythroid, gene, expression, and, differentiation])]). relacion([sujeto(['Oncogenic', transformation, usually]), verbo([inhibits]), complemento([normal, cell, differentiation, processes])]). relacion([sujeto([1, ',', which]), verbo([binds]), complemento([to, and, represses, 'GATA-1,', a, key, transcriptional, stimulator, of, red, blood, cell, differentiation])]). relacion([sujeto(['We']), verbo([report]), complemento([here, that, the, block, to, differentiation, in, 'MEL', cells, can, be, overcome, by, providing, the, cells, with, additional, 'GATA-1'])]). relacion([sujeto(['A', conditionally, active, form, of, 'GATA-1', can]), verbo([trigger]), complemento([the, cells, to, 'differentiate,', undergo, terminal, cell, 'division,', and, lose, their, tumorigenicity])]). relacion([sujeto(['We', also, show, that, the, gene, for, the, cell, cycle, inhibitor, p21, is, transcriptionally]), verbo([regulated]), complemento([by, 'GATA-1', and, is, a, likely, downstream, effector, of, 'GATA-1', that, helps, to, promote, differentiation, and, proliferation, arrest])]). relacion([sujeto(['Mutations', of, 'Wilms\'', tumour, gene, 1, '(', 'WT1)', in, 'AML', are, rare, and, 'WT1', expression, may, be]), verbo([increased]), complemento([by, other, transcription, factors])]). relacion([sujeto(['PAX2', expression, was]), verbo([found]), complemento([in, 11, of, 43, 'AML', 'samples,', with, a, clear, correlation, of, 'PAX2', with, 'WT1', expression, levels, observed])]). relacion([sujeto(['PAX8', expression, was]), verbo([found]), complemento([in, two, additional, samples])]). relacion([sujeto(['GATA-1', is, the, founding, member, of, a, transcription, factor, family, that]), verbo([regulates]), complemento([growth, and, maturation, of, a, diverse, set, of, tissues])]). relacion([sujeto(['GATA-1', is]), verbo([expressed]), complemento([primarily, in, hematopoietic, cells, and, is, essential, for, proper, development, of, erythroid, 'cells,', 'megakaryocytes,', 'eosinophils,', and, mast, cells])]). relacion([sujeto(['Although']), verbo([loss]), complemento([of, 'GATA-1', leads, to, differentiation, arrest, and, apoptosis, of, erythroid, 'progenitors,', absence, of, 'GATA-1', promotes, accumulation, of, immature, megakaryocytes])]). relacion([sujeto(['Recently,', we, and, others]), verbo([have]), complemento([reported, that, mutagenesis, of, 'GATA1', is, an, early, event, in, 'Down', syndrome, '(', 'DS)', leukemogenesis])]). relacion([sujeto(['Future', studies, to, define, the, mechanism, that, results, in, the, high, frequency, of, 'GATA1', mutations, in, 'DS', and, the, role, of, altered, 'GATA1', in, 'TMD', and, 'DS-AMKL', will, shed, light, on, the, multistep, pathway, in, human, leukemia, and, may]), verbo([lead]), complemento([to, an, increased, understanding, of, why, children, with, 'DS', are, markedly, predisposed, to, leukemia])]). relacion([sujeto(['Transcription', factors, 'GATA-1', and, 'GATA-2', are]), verbo([required]), complemento([for, normal, hematopoiesis])]). relacion([sujeto(['The']), verbo([loss]), complemento([of, either, leads, to, embryonic, lethality, in, knockout, mice, because, of, the, failure, of, erythroid, maturation, and, the, expansion, of, 'progenitors,', respectively])]). relacion([sujeto(['As', shown, 'here,', we]), verbo([have]), complemento([analyzed, 'double-knockout', embryos, at, the, yolk, sac, stage, of, development, and, have, shown, that, the, combined, absence, of, these, 'GATA', factors, virtually, ablates, primitive, erythroid, cell, formation])]). relacion([sujeto(['Moreover,', a, 'GATA', 'factor,', either, 'GATA-1', or, 'GATA-2,', is]), verbo([required]), complemento([to, initiate, blood, formation, in, the, embryo])]). relacion([sujeto(['Enforced', expression, of, 'GATA-1', in, hematopoietic, stem, cells]), verbo([led]), complemento([to, loss, of, 'self-renewal', activity, and, the, exclusive, generation, of, 'MegE', lineages])]). relacion([sujeto(['Strikingly,', ectopic, 'GATA-1', reprogrammed, common, lymphoid, progenitors, as, well, as, 'granulocyte/monocyte', '(', 'GM)', progenitors, to, differentiate, into, 'MegE', 'lineages,', while]), verbo([inhibiting]), complemento([normal, lymphoid, or, 'GM', differentiation])]). relacion([sujeto(['GATA-1', upregulated, critical, 'MegE-related', transcription, factors, such, as, 'FOG-1', and, 'GATA-2', in, lymphoid, and, 'GM', 'progenitors,', and, their, 'MegE', development, did, not]), verbo([require]), complemento([&, 'quot;permissive"', erythropoietin, signals])]). relacion([sujeto(['Furthermore,', 'GATA-1']), verbo([induced]), complemento([apoptosis, of, proB, and, myelomonocytic, 'cells,', which, could, not, be, prevented, by, enforced, permissive, 'Bcl-2', or, myeloid, cytokine, signals])]). relacion([sujeto(['Thus,', 'GATA-1', specifically, instructs, 'MegE', commitment, while, excluding, other, fate, outcomes, in, stem, and, progenitor, 'cells,']), verbo([suggesting]), complemento([that, regulation, of, 'GATA-1', is, critical, in, maintaining, multilineage, homeostasis])]). relacion([sujeto(['Mesenchymal', stem, cells, '(', 'MSCs),', precursors, of, diverse, stromal, 'cells,', can, support, hematopoiesis, in, vitro, and, can]), verbo([promote]), complemento([the, implantation, of, hematopoietic, stem, cells, in, vivo, when, 'co-transplanted', with, 'CD34(+)', cells])]). relacion([sujeto(['After']), verbo([maintaining]), complemento([culture, on, mouse, embryonic, 'fibroblasts,', 'CCE', cells, were, plated, in, suspended, culture, system, with, only, differentiation, inductive, agents, and, 'co-culture', system, in, which, 'MSCs', were, added])]). relacion([sujeto(['Compared', with, 'CCE', cell, suspended, 'culture,', the, cells, differentiated, into, embryoid, body, were, obviously]), verbo([enhanced]), complemento([and, there, were, no, 'colony-forming', cells, in, the, 'co-culture', system, of, 'ES', cells, and, 'MSCs'])]). relacion([sujeto(['In', 'addition,', transcription, factor, 'Oct-4', in, 'co-cultured', 'CCE', cells, was]), verbo([expressed]), complemento([and, hematopoietic, 'markers,', 'Flk-1,', 'GATA-1', and, 'beta-H1,', were, negative])]). relacion([sujeto(['It', is, concluded, that, 'MSCs']), verbo([inhibit]), complemento([the, initial, differentiation, of, 'ESC', and, enhance, hematopoietic, differentiation, ability, of, the, 'co-cultured', 'ES', cells])]). relacion([sujeto(['Outside', the, haematopoietic, 'system,', 'Gata1', is, only]), verbo([expressed]), complemento([in, the, 'Sertoli', cells, of, the, testis])]). relacion([sujeto(['Surprisingly,', 'Gata1', null, testes, developed, to, be, morphologically, 'normal,', spermatogenesis, was, not, obviously, affected, and, expression, levels, of, putative, 'Gata1']), verbo([target]), complemento(['genes,', and, other, 'Gata', 'factors,', were, not, altered])]). relacion([sujeto(['Smad7,', an, inhibitor, of, transforming, growth, factor, beta, superfamily, 'signaling,', is]), verbo([induced]), complemento([by, bone, morphogenetic, protein, '(', 'BMP)', in, an, inhibitory, feedback, loop])]). relacion([sujeto(['One', of, these, contains, several]), verbo([conserved]), complemento(['Smad1', and, 'Smad4', binding, sites, that, cooperate, to, mediate, 'BMP-dependent', 'induction,', most, likely, in, the, absence, of, 'DNA', binding, partners])]). relacion([sujeto(['The', third, 'BRE', '(', 'I-BRE)', resides, in, the, first, intron, and, contains, 'GATA', factor]), verbo([binding]), complemento([sites])]). relacion([sujeto(['GATA-1,', -, 5, ',', or, -, 6, is]), verbo([required]), complemento([for, strong, activation, of, 'I-BRE,', and, we, show, that, they, assemble, with, 'Smad1', on, the, 'I-BRE', in, living, cells])]). relacion([sujeto(['Activation', of, the, 'I-BRE', is]), verbo([mediated]), complemento([by, a, specific, region, in, 'GATA-5', and, -, 6, but, does, not, require, direct, physical, interaction, with, 'Smad1'])]). relacion([sujeto(['This', correlates, with, regulation, of, the, 'Smad7', 'gene,', which, is]), verbo([induced]), complemento([at, lower, 'BMP', concentrations, in, 'GATA-expressing', cell, lines, compared, to, 'non-GATA-expressing', lines])]). relacion([sujeto(['We']), verbo([found]), complemento([a, novel, 'polymorphism,', -, 66, 'T/C,', in, the, promoter, region, of, human, 'FcepsilonRIalpha,', the, specific, component, of, the, high, affinity, receptor, for, 'IgE', '(', 'FcepsilonRI),', which, is, essential, for, the, cell, surface, expression, of, 'FcepsilonRI', and, the, binding, of, 'IgE', 'Ab'])]). relacion([sujeto(['When', the, effect, of, the, single, nucleotide, replacement, on, the, promoter, function, was, 'analyzed,', the, transcription, activity, of, the, 'T', allele, promoter, was]), verbo([found]), complemento([to, be, higher, than, that, of, the, 'C', allele, 'promoter,', and, was, markedly, 'up-regulated', by, the, overexpression, of, 'GATA-1', when, compared, with, the, 'C', allele, promoter])]). relacion([sujeto(['This', is, probably, because, the, promoter, with, 'T', at, -, 66]), verbo([has]), complemento([an, additional, 'GATA-1-binding', motif, in, the, 'region,', which, may, assure, higher, affinity, of, the, transcription, factor, to, the, promoter])]). relacion([sujeto(['In', accordance, with, 'this,', 'EMSA', actually, indicated, that, 'GATA-1']), verbo([bound]), complemento([to, the, 'T', allele, probe, '(', -, 80, /, -, 59, ')', with, the, affinity, higher, than, that, to, the, 'C', allele, probe])]). relacion([sujeto(['Statistical', analysis]), verbo([suggested]), complemento([that, a, significant, portion, of, nonallergic, individuals, has, heterozygous, -, 66, 'T/C', 'genotype,', while, most, of, allergic, individuals, have, homozygous, -, 66, 'T/T', genotype, in, 'Japanese', population])]). relacion([sujeto(['Ets-family', genes]), verbo([have]), complemento([been, implicated, in, 'leukemia,', as, well, as, in, normal, hematopoiesis])]). relacion([sujeto(['ERF', is, an, 'ets-related', gene, that, represses, transcription, and, is]), verbo([regulated]), complemento([by, 'MAPK', phosphorylation, through, its, effect, on, 'ERF', 'sub-cellular', localization])]). relacion([sujeto(['K562', and, 'HEL', cells]), verbo([expressing]), complemento(['ERF', expressed, elevated, levels, of, the, 'erythroid-specific', markers, 'CD71', and, 'Glycophorin', 'A,', as, well, as, hemoglobin, and, 'GATA1'])]). relacion([sujeto(['Treatment', with, the, 'Erk', kinase, inhibitor, 'PD98058', further]), verbo([enhanced]), complemento([the, erythroid, phenotype, in, 'ERF-expressing', cells, and, cells, expressing, a, 'non-phosphorylatable', 'ERF', mutant, exhibited, an, even, more, enhanced, phenotype])]). relacion([sujeto(['These', results, are, consistent, with, the, fact, that, 'ERF', function, is]), verbo([regulated]), complemento([by, 'MAPK,', and, suggest, that, the, effect, of, the, 'MAPK', pathway, in, erythroid, differentiation, is, partially, mediated, by, 'ERF'])]). relacion([sujeto(['The', effect, of, 'ERF', is, similar, to, the, one, shown, for, 'ETS1', and, opposite, to, the, 'FLI1', function, in, these, 'cells,']), verbo([suggesting]), complemento([that, several, ets, genes, may, play, key, roles, in, hematopoietic, differentiation])]). relacion([sujeto(['To', ascertain, whether, strict, control, of, 'GATA-1', expression, level, is, necessary, for, achieving, proper, 'erythropoiesis,', we, established, transgenic, mouse, lines]), verbo([expressing]), complemento([green, fluorescent, protein, '(', 'GFP)', under, the, control, of, the, 'GATA-1', gene, hematopoietic, regulatory, domain])]). relacion([sujeto(['We', examined, the, 'GATA-1', expression, level, by, exploiting, the, transgenic, mice, and]), verbo([found]), complemento([2, 'GFP-positive', hematopoietic, progenitor, fractions, in, the, bone, marrow])]). relacion([sujeto(['Since', the, intensity, of, green, fluorescence, correlates, well, with, the, expression, level, of, 'GATA-1,', these, results, indicate, that, 'GATA-1', is, highly]), verbo([expressed]), complemento([in, erythroid, 'colony-forming', unit, '(', 'CFU-E)', but, low, in, erythroid, 'burst-forming', unit, '(', 'BFU-E),', suggesting, that, the, incremental, expression, of, 'GATA-1', is, required, for, the, formation, of, erythroid, progenitors])]). relacion([sujeto(['SCL/Tal-1', is, a, 'helix-loop-helix', '(', 'HLH)', transcription, factor]), verbo([required]), complemento([for, blood, cell, 'development,', whose, abnormal, expression, is, responsible, for, induction, of, 'T-cell', acute, lymphoblastic, leukemia])]). relacion([sujeto(['We', show, here, that, 'SCL/Tal-1', is, a, key]), verbo([target]), complemento([of, caspases, in, developing, erythroblasts])]). relacion([sujeto(['Expression', of, a, 'caspase-resistant', 'SCL/Tal-1', in, erythroid, progenitors, was, able, to]), verbo([prevent]), complemento([amplification, of, caspase, 'activation,', 'GATA-1', degradation, and, impaired, erythropoiesis, induced, by, growth, factor, deprivation, or, death, receptor, triggering])]). relacion([sujeto(['The', potent, proerythropoietic, activity, of, uncleavable, 'SCL/Tal-1', was, clearly, evident, in, the, absence, of, 'erythropoietin,', a, condition, that, did, not, allow, survival, of, normal, erythroid, cells, or, expansion, of, erythroblasts]), verbo([expressing]), complemento(['caspase-resistant', 'GATA-1'])]). relacion([sujeto(['In', the, absence, of, 'erythropoietin,', cells]), verbo([expressing]), complemento(['caspase-resistant', 'SCL/Tal-1', maintain, high, levels, of, 'Bcl-X(L),', which, inhibits, amplification, of, the, caspase, cascade, and, mediates, protection, from, apoptosis])]). relacion([sujeto(['Although', 'GATA-2']), verbo([regulates]), complemento([hematopoietic, stem, cell, 'function,', mechanisms, controlling, 'GATA-2', expression, are, undefined])]). relacion([sujeto(['Using', chromatin, immunoprecipitation, 'analysis,', we, show, that, 'GATA-1']), verbo([binds]), complemento([a, highly, restricted, upstream, region, of, the, approximately, 70, -, kb, 'GATA-2', 'domain,', despite, &, 'gt;80', 'GATA', sites, throughout, the, domain])]). relacion([sujeto(['GATA-2', also]), verbo([binds]), complemento([this, region, in, the, absence, of, 'GATA-1'])]). relacion([sujeto(['GATA-1', also, displaces, 'CREB-binding', protein, '(', 'CBP),', despite, the, fact, that, 'GATA-1']), verbo([binds]), complemento(['CBP', in, other, contexts])]). relacion([sujeto(['The', erythroid, transcription, factor, 'GATA-1', is, also]), verbo([expressed]), complemento([in, 'Sertoli', cells, of, the, testis])]). relacion([sujeto(['The', testicular, expression, of, 'GATA-1', is]), verbo([regulated]), complemento([in, a, developmental, and, spermatogenic, 'stage-specific', manner])]). relacion([sujeto(['We']), verbo([found]), complemento([that, 'GATA-1', expression, in, 'Sertoli', cells, is, markedly, decreased, concomitant, with, the, emergence, of, elongated, spermatids, in, the, seminiferous, tubules])]). relacion([sujeto(['Oncogenes']), verbo([involved]), complemento([in, the, development, of, hematological, malignancies, were, first, discovered, through, the, study, of, experimental, leukemias, induced, in, animals, by, retroviruses])]). relacion([sujeto(['The', discovery, that, some, of, these, genes, were, located, at, the, breakpoints, of, chromosome, rearrangements, in, human, 'malignancies,', such, as, the, 'MYC', gene, in, 'Burkitt\'s', lymphoma, and, the, 'ABL', gene, in, chronic, myeloid, leukemia, '(', 'CML)']), verbo([has]), complemento([suggested, that, chromosome, abnormalities, were, causally, implicated, in, the, pathogenesis, of, human, diseases])]). relacion([sujeto(['Numerous', nonrandom, somatically, acquired, chromosomal, translocations, or, inversions]), verbo([have]), complemento([been, identified, in, human, leukemias])]). relacion([sujeto(['Chromosome', translocations, can]), verbo([lead]), complemento([to, the, deregulated, expression, of, a, normal, gene, 'product,', but, in, most, cases, of, 'leukemia,', chromosome, rearrangements, result, in, the, expression, of, a, chimeric, fusion, protein])]). relacion([sujeto(['Oncogene', products]), verbo([associated]), complemento([with, acute, leukemias, are, often, transcription, factors, while, tyrosine, kinases, and, antiapoptotic, proteins, are, more, commonly, activated, or, overexpressed, in, chronic, leukemias, and, in, lymphomas])]). relacion([sujeto(['But', the, most, exciting]), verbo([finding]), complemento([was, the, discovery, of, activating, point, mutations, in, tyrosine, kinase, receptors, such, as, 'FLT3', and, 'c-KIT', in, acute, leukemia])]). relacion([sujeto(['Treatment', of, leukemia, could, therefore, benefit, from, new, therapeutic, approaches]), verbo([targeting]), complemento([the, function, of, specific, oncogene, products, as, already, demonstrated, for, 'CML', and, acute, promyelocytic, leukemia])]). relacion([sujeto(['Recently,', acquired, mutations, in, the, 'N-terminal', activation, domain, of, the, 'GATA-1', 'gene,', encoding, the, 'erythroid/megakaryocytic', transcription, factor, 'GATA-1,']), verbo([have]), complemento([been, reported, in, 'Down', 'syndrome-related', 'AMKL', '(', 'DS-AMKL)'])]). relacion([sujeto(['In', the, 'DS-AMKL', cell, 'line,', 'MGS,', which, itself]), verbo([expresses]), complemento([only, a, truncated, mutant, of, 'GATA-1,', expression, of, 'full-length', 'GATA-1', induced, the, differentiation, toward, the, erythroid, lineage])]). relacion([sujeto(['However,', expression, of, the, short, form, of, 'GATA-1', did, not]), verbo([induce]), complemento([erythroid, differentiation])]). relacion([sujeto(['The', developmentally]), verbo([regulated]), complemento([mammalian, 'beta-globin', genes, are, activated, by, a, distant, locus, control, 'region/enhancer'])]). relacion([sujeto(['The', 'HS2', 'MAREs', are]), verbo([required]), complemento([for, nucleosome, mobilization, and, histone, hyperacetylation, at, the, distant, promoter])]). relacion([sujeto(['Nucleosome', mobilization, also]), verbo([requires]), complemento([the, promoter, 'TATA', 'box,', and, is, independent, of, histone, hyperacetylation])]). relacion([sujeto(['In', 'contrast,', promoter, hyperacetylation]), verbo([requires]), complemento([the, promoter, 'GATA-1,', and, 'CACC-factor', activator, 'motifs,', as, well, as, the, 'TATA', box])]). relacion([sujeto(['ChIP', analysis]), verbo([reveals]), complemento([that, 'NF-E2', is, associated, with, the, active, 'epsilon-globin', 'promoter,', which, lacks, an, 'NF-E2', binding, 'sequence,', in, a, 'TATA', box, and, 'HS2/MARE-dependent', fashion])]). relacion([sujeto(['The', results, emphasize, 'MARE-TATA', box, interactions, in, the, recruitment, of, complexes, modifying, promoter, chromatin, for, transcription, activation, and, imply, close, physical, interaction, between, widely, separated, regulatory, sequences]), verbo([mediated]), complemento([through, these, sites])]). relacion([sujeto(['As', most, transcription, 'factors,', 'GATA-1', activities, are]), verbo([mediated]), complemento([by, interactions, with, multiple, proteins])]). relacion([sujeto(['Those', identified, so, far]), verbo([associate]), complemento([with, the, 'zinc-finger', domain, 'and/or', surrounding, sequences])]). relacion([sujeto(['In', 'contrast,', no, proteins]), verbo([interacting]), complemento([with, the, 'N-terminal', domain, have, been, identified, although, several, evidences, suggest, its, involvement, in, the, control, of, hematopoiesis])]). relacion([sujeto(['In', an, attempt, to, identify, proteins, that]), verbo([interact]), complemento([with, the, 'N-terminal', transactivation, domain, of, 'GATA-1,', a, random, phage, peptide, library, was, screened, with, recombinant, 'GATA-1', protein, and, the, sequence, of, a, selected, peptide, was, used, for, database, protein, sequence, retrieval])]). relacion([sujeto(['We', show, that, 'Nef']), verbo([binds]), complemento(['GATA-1', and, 'GATA-3', in, vitro, in, virtue, of, its, sequence, homology, with, pep5])]). relacion([sujeto(['Asthma', is, characterized, by, an]), verbo([increased]), complemento([production, of, 'eosinophil-active', 'C-C', chemokines, by, the, airway, epithelium])]). relacion([sujeto(['Recent', studies]), verbo([have]), complemento([identified, the, presence, of, important, quantities, of, labile, zinc, in, the, conducting, airways])]). relacion([sujeto(['DMPS', and, 'TPEN', specifically]), verbo([inhibited]), complemento([the, production, of, 'eotaxin,', regulated, on, 'activation,', normal, 'T-cell', 'expressed,', and, presumably, 'secreted,', and, monocyte, chemotactic, 'protein-1', in, 'TNF-alpha-stimulated', respiratory, epithelial, cells, and, fibroblasts, through, labile, zinc, chelation])]). relacion([sujeto(['The', inhibitory, effects, of, 'DMPS', and, 'TPEN', were]), verbo([associated]), complemento([with, the, decreased, binding, of, the, 'zinc-finger', transcription, factor, 'GATA-1,', whereas, no, change, in, 'NF-kappaB', activation, was, observed])]). relacion([sujeto(['Together', these, results, demonstrate, that, modulation, of, the, labile, pool, of, zinc, can]), verbo([regulate]), complemento([gene, expression, and, protein, synthesis, of, 'C-C', chemokines, in, lung, epithelial, cells, and, fibroblasts])]). relacion([sujeto(['Mutations', in, 'GATA1']), verbo([have]), complemento([been, reported, in, acute, megakaryoblastic, leukaemia, in, 'Down\'s', syndrome])]). relacion([sujeto(['Friend', leukemia, integration, 1, '(', 'Fli-1)', is, a, member, of, the, 'Ets', family, of, transcriptional, activators, that]), verbo([has]), complemento([been, shown, to, be, an, important, regulator, during, megakaryocytic, differentiation])]). relacion([sujeto(['We', undertook, a, 'two-hybrid', screen, of, a, 'K562', cDNA, library, to, identify, transcription, factors, that]), verbo([interacted]), complemento([with, 'Fli-1', and, were, potential, regulators, of, megakaryocyte, development])]). relacion([sujeto(['Here', we]), verbo([report]), complemento([the, physical, interaction, of, 'Fli-1', with, 'GATA-1,', a, 'well-characterized,', zinc, finger, transcription, factor, critical, for, both, erythroid, and, megakaryocytic, differentiation])]). relacion([sujeto(['We', map, the, minimal, domains]), verbo([required]), complemento([for, the, interaction, and, show, that, the, zinc, fingers, of, 'GATA-1', interact, with, the, 'Ets', domain, of, 'Fli-1'])]). relacion([sujeto(['GATA-1']), verbo([has]), complemento([previously, been, shown, to, interact, with, the, 'Ets', domain, of, the, 'Fli-1-related', protein, 'PU'])]). relacion([sujeto([1, ',', and, the, two, proteins, appear, to]), verbo([inhibit]), complemento([each, 'other\'s', activity])]). relacion([sujeto(['In', 'contrast,', we, demonstrate, that, 'GATA-1', and, 'Fli-1', synergistically]), verbo([activate]), complemento([the, 'megakaryocyte-specific', promoters, 'GPIX', and, 'GPIbalpha', in, transient, transfections])]). relacion([sujeto(['Quantitative', electrophoretic, mobility, shift, assays, using, oligonucleotides, derived, from, the, 'GPIX', promoter, containing, 'Ets', and, 'GATA']), verbo([binding]), complemento([motifs, reveal, that, 'Fli-1', and, 'GATA-1', exhibit, cooperative, 'DNA', binding, in, which, the, binding, of, 'GATA-1', to, 'DNA', is, increased, approximately, 26, -, fold, in, the, presence, of, 'Fli-1', '(', from, 4.2, to, 0.16, 'nM),', providing, a, mechanism, for, the, observed, transcriptional, synergy])]). relacion([sujeto(['Overexpression', of, 'Fli-1']), verbo([induced]), complemento([the, expression, of, the, endogenous, 'GPIX', and, 'GPIbalpha', genes, as, measured, by, 'Northern', blot, and, 'fluorescence-activated', cell, sorter, analysis])]). relacion([sujeto(['This', work]), verbo([suggests]), complemento([that, 'Fli-1', and, 'GATA-1', work, together, to, activate, the, expression, of, genes, associated, with, the, terminal, differentiation, of, megakaryocytes])]). relacion([sujeto(['YY1', is, a, ubiquitously]), verbo([expressed]), complemento([multifunctional, transcription, factor, that, is, involved, in, both, positive, and, negative, regulation, of, gene, expression, as, well, as, initiation, of, transcription])]). relacion([sujeto(['When', residues, 114, -, 193, ',', which, sequence, includes, a, portion, of, the, activation, region, and, most, of, the, 'Gly/Lys-rich', 'region,', were, 'lacking,', transactivation, activity]), verbo([decreased]), complemento(['somewhat,', but, the, further, deletion, in, the, activation, region, '(', of, residues, 56, -, 113, ')', did, not, cause, further, decrease, of, the, activity])]). relacion([sujeto(['On', the, other, 'hand,', 'N-terminus', of, the, activation, region, '(', 1, -, 78, /, 100, -, 106, ')', did, not]), verbo([have]), complemento([transactivation, activity, by, itself, as, well, as, synergistic, activity, with, an, erythroid, specific, transcription, factor, 'GATA-1'])]). relacion([sujeto([32, 'D', cells, grown, for, 1, year, in, 'interleukin-3', '(', 'IL-3)', and, granulocyte, 'colony-stimulating', factor, '(', 'G-CSF)', generated, the, 32, 'D', 'Ro', cell, line, which]), verbo([retained]), complemento([the, parental, mast, cell, phenotype, but, lost, ability, to, generate, erythroid, cells, in, response, to, erythropoietin, '(', 'EPO)'])]). relacion([sujeto(['In', order, to, clarify, the, mechanisms, underlying, such, 'restriction,', we, compared, 32, 'D', and, 32, 'D', 'Ro', cells, for, their, capacity, to]), verbo([express]), complemento(['erythroid-specific', transcription, factors, '(', 'Gata1,', 'Gata2,', 'Scl,', 'Nef2,', 'Eklf,', and, 'Id)', and, the, capacity, of, short, exposure, to, 5, -, azacytidine, '(', 5, -, 'AzaC)', to, reactivate, erythroid, differentiation, potential, in, 32, 'D', 'Ro', cells])]). relacion([sujeto(['By', 'Northern', 'analysis,', the, two, cell, lines]), verbo([expressed]), complemento([similar, levels, of, all, these, genes])]). relacion([sujeto(['All', the, 10, 'EPO-responsive', cell, lines, independently, isolated, from, 5, -, 'AzaC-treated', 32, 'D', 'Ro', cells, had, erythroid, morphology, and]), verbo([expressed]), complemento([high, levels, of, 'alpha-', and, 'beta-globin'])]). relacion([sujeto(['Therefore,', 5, -, 'AzaC', treatment]), verbo([reactivates]), complemento([the, potential, of, the, 'myeloid-restricted', 32, 'D', 'Ro', cells, to, generate, 'EPO-responsive', erythroid, clones, suggesting, that, gene, methylation, played, an, important, role, in, the, 'G-CSF-mediated', 'restriction/activation', of, the, differentiation, potential, of, these, cells])]). relacion([sujeto(['Here', we]), verbo([have]), complemento([employed, a, culture, 'system,', that, faithfully, recapitulates, red, blood, cell, differentiation, in, 'vitro,', to, follow, the, kinetics, of, 'GATA-1', and, 'c-myb', expression])]). relacion([sujeto(['We', show, that, 'c-myb', 'proto-oncogene', expression, is, high, in, progenitors, and, effectively, downregulated, at, the, time, when]), verbo([nuclear]), complemento(['GATA-1', accumulates, and, cells, differentiate, into, erythrocytes])]). relacion([sujeto(['Additionally,', we, identified, two, 'GATA-1']), verbo([binding]), complemento([sites, within, the, 'c-myb', promoter, and, demonstrate, that, 'GATA-1', protein, binds, to, these, sites, in, vitro])]). relacion([sujeto(['Furthermore,', 'GATA-1', represses, 'c-myb', expression, through, one, of, the, 'GATA-1']), verbo([binding]), complemento([sites, in, transient, transfection, experiments, and, this, requires, 'FOG-1'])]). relacion([sujeto(['Thus,', our, study]), verbo([provides]), complemento([evidence, for, a, direct, molecular, link, between, 'GATA-1', activity, and, 'c-myb', 'proto-oncogene', expression, during, terminal, red, cell, differentiation])]). relacion([sujeto(['In', previous, 'reports,', we, demonstrated, the, expression, of, 'PDGF', receptors, on, platelets, and, megakaryocytic, cells, and, that, 'PDGF']), verbo([enhanced]), complemento([the, proliferation, of, megakaryocytic, progenitor, cells])]). relacion([sujeto(['RT-PCR/Southern', blot, analysis, and, 'Real-time', 'PCR', demonstrated, that, 'PDGF']), verbo([increased]), complemento([the, mRNA, expression, of, 'c-Fos,', 'GATA-1', and, 'NF-E2,', but, not, 'PU'])]). relacion([sujeto(['The', activation, was, confirmed, at, the, protein, level, by, 'Western', blot, analysis, of, both, total, cell, and]), verbo([nuclear]), complemento([lysates])]). relacion([sujeto(['The', addition, of]), verbo([increasing]), complemento([concentrations, of, 'Tyrphostin', 'AG1295,', an, inhibitor, of, 'PDGF', receptor, 'kinase,', blocked, the, stimulatory, effect, of, 'PDGF', on, the, mRNA, and, protein, expressions, of, these, transcription, factors])]). relacion([sujeto(['The', 'up-regulation', of, 'c-Fos,', 'GATA-1', and, 'NF-E2', protein, by, 'PDGF', was]), verbo([inhibited]), complemento([by, actinomycin, 'D', and, 'cycloheximide,', suggesting, that, mRNA, and, protein, synthesis, might, be, involved, in, the, mechanism])]). relacion([sujeto(['Our', data]), verbo([suggest]), complemento([a, direct, stimulatory, effect, of, 'PDGF', on, 'c-Fos,', 'GATA-1', and, 'NF-E2', expressions, and, we, speculate, that, these, transcription, factors, might, be, involved, in, the, signal, transduction, of, 'PDGF', on, the, regulation, of, megakaryocytopoiesis])]). relacion([sujeto(['Recently,', acquired, mutations, in, exon, 2, of, 'GATA1,', an, 'X-linked', gene, encoding, a, transcription, factor, that]), verbo([promotes]), complemento([megakaryocytic, 'differentiation,', were, described, in, 6, 'DS', patients, with, 'AMKL'])]). relacion([sujeto(['The', mutations]), verbo([prevent]), complemento([the, synthesis, of, the, 'full-length', 'GATA1,', but, allow, the, synthesis, of, a, shorter, 'GATA1', protein, '(', 'GATA1s)', that, lacks, the, transactivation, domain])]). relacion([sujeto(['To', test, whether, mutated, 'GATA1', is]), verbo([involved]), complemento([in, the, initiation, of, clonal, megakaryoblastic, proliferation, or, in, the, progression, to, 'AMKL,', we, screened, 35, 'DS', patients, with, either, 'AMKL', or, 'TMD', and, 7, 'non-DS', children, with, 'AMKL', for, mutations, in, exon, 2, of, 'GATA1'])]). relacion([sujeto(['Analysis', revealed, various, types, of, mutations, in, 'GATA1,', including, 'deletion/insertions,', splice, 'mutations,', and, nonsense, and, missense, point, 'mutations,', all, of, which]), verbo([prevent]), complemento([the, generation, of, 'full-length', 'GATA1,', but, preserve, the, translation, of, 'GATA1s'])]). relacion([sujeto(['These', findings]), verbo([suggest]), complemento([that, acquired, intrauterine, inactivating, mutations, in, 'GATA1', and, generation, of, 'GATA1s', cooperate, frequently, with, trisomy, 21, in, initiating, megakaryoblastic, 'proliferation,', but, are, insufficient, for, progression, to, 'AMKL'])]). relacion([sujeto(['GATA-1', is, a, transcription, factor, essential, for, erythroid, cell, 'development,', and, knockdown, of, 'GATA-1', gene, results, in, maturation]), verbo([arrest]), complemento([and, transformation, of, erythroblasts])]). relacion([sujeto(['To', clarify, the, mechanism, that, gives, rise, to, this, abnormal, 'phenotype,', genes, that, are, aberrantly]), verbo([expressed]), complemento([in, the, spleen, of, heterozygous, 'GATA-1', knockdown, mutant, mouse, '(', referred, to, as, 'GATA-1', mutant, 'mouse)', were, identified, by, using, cDNA, array])]). relacion([sujeto(['One', of, these, 'genes,', 'YB-1,', was]), verbo([found]), complemento([to, be, highly, expressed, in, the, spleen, of, 'GATA-1', mutant, mouse])]). relacion([sujeto(['Furthermore,', both, 'GATA-1', and, 'GATA-2,', which, were, transiently]), verbo([expressed]), complemento([in, 'COS-7', 'cells,', bound, to, this, element, and, activated, the, 'YB-1', promoter, through, this, element])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, 'YB-1', functions, under, the, regulation, of, 'GATA', factors, in, erythroid, differentiation, and, aberrant, expression, of, 'YB-1', gene, may, result, in, dyserythropoiesis])]). relacion([sujeto(['We']), verbo([have]), complemento([reported, that, a, novel, 'c-Myc', binding, 'protein,', 'AMY-1,', stimulated, the, transcription, activity, of, 'c-Myc', and, was, translocated, from, the, cytoplasm, to, the, nucleus, in, a, 'c-Myc-dependent', manner])]). relacion([sujeto(['Sp1', in, both, cell, lines, and, 'GATA-1', only, in, 'K562', cells, were, identified, as, proteins]), verbo([binding]), complemento([to, these, sites, by, a, mobility, shift, assay])]). relacion([sujeto(['Furthermore,', it, was]), verbo([found]), complemento([that, 'GATA-1', stimulated, 'AMY-1', expression, synergistically, with, 'Sp1', in, ectopically, expressed, insect, cells, and, that, both, proteins, were, associated, in, 'K562', cells])]). relacion([sujeto(['To', further, characterize, the, differentiation]), verbo([inducing]), complemento([properties, of, 'EDRF1', and, demonstrate, its, functional, pathway, involved, in, regulation, of, globin, gene, expression])]). relacion([sujeto(['In', antisense, 'EDRF1,', overexpression, of, 'HEL', 'cells,', significant]), verbo([loss]), complemento([of, 'alpha-,', 'gamma-globin', mRNA, synthesis, was, observed])]). relacion([sujeto(['The', transcription, of, endogenous, 'GATA-1', and, 'NF-E2', mRNA, expression, were]), verbo([maintained]), complemento([at, the, same, levels, compared, with, control, experiments])]). relacion([sujeto(['The', results]), verbo([suggested]), complemento([that, 'EDRF1', regulated, 'alpha-', and, 'gamma-globin', gene, synthesis, by, modulating, 'DNA-binding', activity, of, 'GATA-1', transcription, factor])]). relacion([sujeto(['We']), verbo([have]), complemento([cloned, the, genomic, 'DNA', encoding, the, human, 'NeuAc', 'alpha2,3Gal', 'beta1,3GalNAc', 'alpha2,6-sialyltransferase', '(', hST6GalNAc, 'IV)', and, analysed, its, structure])]). relacion([sujeto(['The', hST6GalNAc, 'IV', gene, was]), verbo([found]), complemento([to, span, about, 9, kb, and, to, be, composed, of, six, exons])]). relacion([sujeto(['Sequence', analysis, of, the, 5, '\'', -, flanking, region, of, this, gene, lacked, canonical, 'TATA', and, 'CAAT', 'boxes,', but, contained, several, putative]), verbo([binding]), complemento([sites, for, transcription, factors, 'SP1,', 'MZF1,', 'GATA1,', 'LMO2COM,', 'NFAT,', 'HFH8', and, 'USF,', etc])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([cell, 'type-specific', regulation, of, the, basal, hST6GalNAc, 'IV', promoter, activity])]). relacion([sujeto(['The', platelet, marginal, band, consists, of, a, single, peripheral, microtubule, '(', 'MT)', that, is, wound, in, 8, to, 12, coils, and]), verbo([maintains]), complemento([discoid, cell, shape])]). relacion([sujeto(['beta1-tubulin+/-', platelets]), verbo([have]), complemento([normal, ratios, of, 'beta-tubulin', isotypes, but, the, marginal, band, is, half, the, normal, 'thickness,', which, is, sufficient, to, maintain, elliptical, cell, shape])]). relacion([sujeto(['Thus,', a, threshold, 50, '%', or, less, of, the, normal, amount, of, 'beta1-tubulin', is]), verbo([required]), complemento([to, preserve, marginal, band, integrity, and, cell, shape])]). relacion([sujeto(['beta1-tubulin-/-', platelets]), verbo([have]), complemento([normal, size, and, contents, and, show, no, defects, in, serotonin, release, or, aggregation])]). relacion([sujeto(['Together,', these, findings, highlight, the, essential, requirements, of, the, 'MK/platelet-restricted', 'beta1-tubulin', isoform, in, platelet, structure, and]), verbo([suggest]), complemento([that, spherocytosis, does, not, impair, many, aspects, of, platelet, function])]). relacion([sujeto(['Children', with, constitutional, trisomy, 21, '(', 'Down', 'syndrome)']), verbo([have]), complemento([an, approximately, 500, -, fold, increased, risk, of, developing, acute, megakaryoblastic, leukemia, '(', 'AMKL),', a, form, of, acute, myeloid, leukemia])]). relacion([sujeto(['These', findings]), verbo([suggest]), complemento([a, model, of, malignant, transformation, in, 'Down', syndrome, 'AMKL', in, which, 'GATA1', mutations, are, an, early, event, and, 'AMKL', arises, from, latent, 'TL', clones, following, initial, apparent, remission])]). relacion([sujeto(['To', investigate, the, action, of, 'Ginsenosides', '(', 'GS)', in]), verbo([inducing]), complemento([transcription, factor, 'c-fos', and, 'GATA-1', to, explore, the, mechanism, of, 'GS', in, hematopoietic, cells])]). relacion([sujeto(['The', combining, reaction, of, transcription, factors, 'c-fos', and, 'GATA-1', with]), verbo([nuclear]), complemento([protein, antigen, were, analyzed, by, 'Western', 'Blot', after, being, treated, by, 'GS'])]). relacion([sujeto(['(', 1, ')', 'GS', '(', 10, 'micrograms/ml)', could]), verbo([stimulate]), complemento([and, promote, proliferation, of, 3, cell, lines, with, significant, difference, between, 'GS', and, 'non-GS', control, '(', 'P', &, 'lt;', 0.05, in, 'all)', in, both, 'MTT', test, and, colony, assay])]). relacion([sujeto(['(', 2, ')', 'After', treatment, with, 'GS,', 'c-fos', protein, in, 'HL-60,', 'K562', and, 'Meg-01', cell, lines, was]), verbo([increased]), complemento([by, 1.5, ',', 2.0, and, 2.5, fold, 'respectively,', while, 'U937', cell, did, not, express, 'c-fos'])]). relacion([sujeto(['(', 3, ')', 'Except', that, 'U937', cell, 'hadn\'t']), verbo([expressed]), complemento(['GATA-1,', the, other, cell, lines, after, the, treatment, by, 'GS,', the, 'GATA-1', protein, level, was, elevated, to, 1.5, ',', 2.1, and, 1.3, fold, of, that, before, treatment])]). relacion([sujeto(['The', proliferation, of, three, lines, initiated, by, 'GS', was]), verbo([involved]), complemento([in, transcription, factor, 'c-fos', or, 'GATA-1,', which, could, pay, the, role, in, the, 'GS', induced, 'up-regulation', correlated, with, proliferation, and, differentiation, of, hematopoiesis])]). relacion([sujeto(['To', identify, such, 'factors,', we, used, the, 'K562', system, in, which, megakaryocyte, lineage, commitment, is, dependent, on, sustained, extracellular, regulatory, kinase, '(', 'ERK)', activation, and, is]), verbo([inhibited]), complemento([by, stromal, cell, contact])]). relacion([sujeto(['Enforced', 'RUNX1', expression, in, 'K562', cells]), verbo([enhanced]), complemento([the, induction, of, the, megakaryocytic, integrin, proteins, alphaIIb, and, alpha2])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, 'RUNX1', may, participate, in, the, programming, of, megakaryocytic, lineage, commitment, through, functional, and, physical, interactions, with, 'GATA', transcription, factors])]). relacion([sujeto(['Here', it, is, shown, that, the, phenotype, of, adult, mice, lacking, the, first, enhancer, '(', 'DNA', hypersensitive, site, 'I)', and, the, distal, promoter, of, the, 'GATA-1', gene, '(', neo, 'Delta', 'HS', or, 'GATA-1(low)', 'mutants)']), verbo([reveals]), complemento([defects, in, mast, cell, development])]). relacion([sujeto(['We', recently]), verbo([reported]), complemento([that, mutations, in, the, transcription, factor, 'GATA1', are, associated, with, 'DS-AMKL'])]). relacion([sujeto(['Here', we]), verbo([report]), complemento([that, 'GATA1', is, mutated, in, the, 'TMD', blasts, from, every, infant, examined])]). relacion([sujeto(['We', show, here, that, 'FLI-1', represses, the, transcriptional, activity, of, the, 'beta-globin', gene, promoter, in, 'MEL', cells, and]), verbo([interacts]), complemento([with, two, of, its, critical, 'transactivators,', 'GATA-1', and, 'EKLF'])]). relacion([sujeto(['Unexpectedly,', 'FLI-1']), verbo([enhances]), complemento([the, stimulating, activity, of, 'GATA-1', on, a, 'GATA-1-responsive', promoter, but, represses, that, of, 'EKLF', on, 'beta-globin', and, an, 'EKLF-responsive', artificial, promoters])]). relacion([sujeto(['This', repressive, effect, of, 'FLI-1']), verbo([requires]), complemento([the, 'ETS', 'DNA', binding, domain, and, its, association, with, either, the, 'N-', or, 'C-terminal', 'domain,', which, themselves, interact, with, 'EKLF', but, not, with, 'GATA-1'])]). relacion([sujeto(['Furthermore,', the, 'FLI-1', 'ETS', domain, alone, behaves, as, an, autonomous, repression, domain, when, linked, to, the, 'Gal4', 'DNA']), verbo([binding]), complemento([domain])]). relacion([sujeto(['Reciprocally,', we, also, show, that, 'EKLF', itself, represses, the, 'FLI-1-dependent', megakaryocytic, 'GPIX', gene, 'promoter,', thus, further]), verbo([suggesting]), complemento([that, functional, 'cross-antagonism', between, 'FLI-1', and, 'EKLF', might, be, involved, in, the, control, of, the, erythrocytic, versus, megakaryocytic, differentiation, of, bipotential, progenitors])]). relacion([sujeto(['In', erythroid, 'cells,', the, 'beta-globin', gene, cluster, undergoes, developmentally]), verbo([regulated]), complemento([hyperacetylation, of, histones, at, the, active, globin, genes, and, the, locus, control, region, '(', 'LCR)'])]). relacion([sujeto(['Restoration', of, 'GATA-1', activity, in, 'G1E', cells]), verbo([led]), complemento([to, a, substantial, increase, in, acetylation, of, histones, 'H3', and, 'H4', at, the, 'beta-globin', promoter, and, the, 'LCR'])]). relacion([sujeto(['Moreover,']), verbo([increases]), complemento([in, histone, acetylation, correlated, with, occupancy, of, 'GATA-1', and, the, acetyltransferase, 'CBP', at, the, locus, in, vivo])]). relacion([sujeto(['Together,', these, results]), verbo([suggest]), complemento([that, 'GATA-1', and, its, cofactor, 'CBP', are, essential, for, the, formation, of, an, 'erythroid-specific', acetylation, pattern, that, is, permissive, for, high, levels, of, gene, expression])]). relacion([sujeto(['HEL', 'cells,', a, human, erythroleukemia, cell, 'line,']), verbo([expressing]), complemento([mainly, the, 'gamma-globin', 'genes,', small, amount, of, 'epsilon-globin', 'gene,', but, not, 'beta-globin', gene])]). relacion([sujeto(['Our', previous, studies, demonstrated, that, 'beta-globin', gene, could, be]), verbo([expressed]), complemento([in, 'HEL', cells, induced, by, hydroxyurea])]). relacion([sujeto(['Here', the]), verbo([binding]), complemento([patterns, of, 'GATA', factors, '(', 'GATA-1', and, 'GATA-2)', to, the, regulatory, elements, of, human, 'beta-globin', gene, were, examined, with, the, nuclear, extracts, from, 'hydroxyurea-induced', and, uninduced, 'HEL', cells])]). relacion([sujeto(['Our', results, showed, in, 'EMSA', assay, that, 'GATA', factors, could]), verbo([bind]), complemento([to, the, core, sequence, of, 'HS2(-10681', to, -, 10971, 'bp),', the, 3, '\'', flanking, sequence, of, 'HS2', 'core(-10323', to, -, 10680, 'bp)', and, the, promoter, of, human, 'beta-globin', 'gene(+20', to, -, 112, 'bp)'])]). relacion([sujeto(['However,', the]), verbo([binding]), complemento([patterns, between, 'hydroxyurea-induced', and, uninduced, 'HEL', cells, were, different])]). relacion([sujeto(['Furthermore,', by, using, 'Western-blot', 'analysis,', our, data, showed, that, the, amount, of, 'GATA-2', was]), verbo([decreased]), complemento([in, 'hydroxyurea-induced', 'HEL', cells])]). relacion([sujeto(['In', contrast, to, 'GATA-2,', the, amount, of, 'GATA-1', was]), verbo([increased]), complemento([in, 'hydroxyurea-induced', 'HEL', cells])]). relacion([sujeto(['GATA-1', may]), verbo([stimulate]), complemento([the, differentiation, of, 'HEL', 'cells,', while, 'GATA-2', can, probably, inhibit, the, differentiation, of, 'HEL', cells])]). relacion([sujeto(['These', mice]), verbo([express]), complemento(['C/EBP', 'alpha,', 'C/EBP', 'beta,', and, 'C/EBP', delta, in, the, bone, marrow, at, levels, similar, to, those, of, their, 'wild-type', 'counterparts,', suggesting, a, lack, of, functional, redundancy, among, the, family, in, vivo])]). relacion([sujeto(['Stable', inducible, expression, of, 'C/EBP', epsilon, and, 'C/EBP', alpha, in, the, murine, fibroblast, cell, line, 'NIH', 3, 'T3']), verbo([activated]), complemento([expression, of, mRNAs, for, 'B9,', 'MCLP,', 'NC,', and, 'NGAL', but, not, for, 'LF'])]). relacion([sujeto(['In', transient, transfections, of, 'C/EBP', epsilon, and, 'C/EBP', 'alpha,', 'B9', was, strongly]), verbo([induced]), complemento([with, weaker, induction, of, the, other, genes])]). relacion([sujeto(['C/EBP', beta, and, 'C/EBP', delta, proteins, weakly]), verbo([induced]), complemento(['B9', 'expression,', but, 'C/EBP', delta, induced, 'NC', expression, more, efficiently, than, the, other, 'C/EBPs'])]). relacion([sujeto(['The', expression, of, 'MBP', was, inefficiently]), verbo([induced]), complemento([by, 'C/EBP', epsilon, alone, and, weakly, induced, with, 'C/EBP', epsilon, and, 'GATA-1,', but, the, addition, of, 'PU'])]). relacion([sujeto(['Gel-shift', analysis, demonstrated]), verbo([binding]), complemento([of, 'PU'])]). relacion([sujeto(['WT1', gene, encodes, a, zinc, finger, transcription, factor, that]), verbo([regulates]), complemento([transcription, of, its, downstream, genes])]). relacion([sujeto(['Some', of]), verbo([target]), complemento([genes, for, 'WT1', are, involved, in, regulating, both, cell, cycle, and, cellular, proliferation, and, differentiation])]). relacion([sujeto(['However,', 'WT1', itself, is]), verbo([regulated]), complemento([by, its, upstream, genes, such, as, 'NF-kappaB', and, 'GATA-1'])]). relacion([sujeto(['Thus', there, exists, a, pathway, of, transcriptional, regulation]), verbo([mediated]), complemento([by, 'WT1,', which, controls, development, of, hematopoietic, system])]). relacion([sujeto(['The', transient, reporter, assay, indicated, that, -, 69, /, +, 4, region, is]), verbo([required]), complemento([for, cell, 'type-specific', transcriptional, regulation, of, mouse, 'beta-chain', gene])]). relacion([sujeto(['EMSA', using, 'Abs', against, transcription, factors, or, competitive, oligonucleotides, demonstrated, that, -, 58, /, -, 40, region, '(', containing, overlapping, three, 'GATA-1', 'sites,', -, 53, /, -, 48, ',', -, 46, /, -, 51, ',', and, -, 42, /, -, 47, ')', and, -, 31, /, -, 26, region, '(', containing, one, 'GATA-1', 'site)', are]), verbo([recognized]), complemento([by, 'GATA-1'])]). relacion([sujeto(['The', promoter, activity, of, 'beta-chain', was]), verbo([decreased]), complemento([by, nucleotide, replacements, of, the, 'GATA-1', sites, in, mouse, mast, cell, line, 'PT18'])]). relacion([sujeto(['Furthermore,', exogenously, produced, 'GATA-1', 'up-regulated', the, promoter, activity, in, 'CV-1', 'cells,', which, are, negative, in, the, 'beta-chain', production, and, the, 'up-regulation', was, apparently]), verbo([suppressed]), complemento([by, 'GATA-1', site, mutations])]). relacion([sujeto(['These', results, indicate, that, cell, 'type-specific', transcription, of, mouse, 'beta-chain', gene, is]), verbo([regulated]), complemento([by, 'GATA-1'])]). relacion([sujeto(['The', levels, of, expression, of, 'GATA-1', and, 'gamma-globin', mRNA, were, significantly]), verbo([increased]), complemento([in, cells, treated, with, progesterone, compared, to, untreated, cells, '(', 1.7, -, to, 2.0, -, 'fold)'])]). relacion([sujeto(['Using', 'anti-transferrin', receptor, and, 'anti-glycophorin', 'A', 'antibodies,', we, verified, that, addition, of, progesterone, did, not]), verbo([cause]), complemento([any, change, in, erythroid, proliferation, and, differentiation])]). relacion([sujeto(['In', 'conclusion,', it, is, possible, that, the]), verbo([increased]), complemento([expression, of, 'gamma-globin', mRNA, after, progesterone, treatment, observed, in, this, study, may, be, related, to, the, increased, 'GATA-1', mRNA, expression])]). relacion([sujeto(['Interactions', of, the, steroid, receptors, with, the, basal, transcriptional, machinery, and, with, transcription, factors, might]), verbo([mediate]), complemento([their, transcriptional, effects])]). relacion([sujeto(['Anthracycline', antitumor, drugs]), verbo([induce]), complemento([erythroid, differentiation, of, the, 'K562', erythroleukemic, cell, line, at, subtoxic, concentrations])]). relacion([sujeto(['Aclacinomycin', '(', 'ACM)']), verbo([stimulates]), complemento([this, process, by, activating, the, erythroid, transcription, factor, 'GATA-1,', that, controls, genes, involved, in, hemoglobin, biosynthesis])]). relacion([sujeto(['The', 'GATA-1', transcription, factor, was, then, monitored, during, erythroid, differentiation]), verbo([induced]), complemento([by, aclacinomycin])]). relacion([sujeto(['It']), verbo([suggests]), complemento([that, anthracyclines, can, induce, the, erythroid, differentiation, of, neoplastic, cells, by, activating, the, transcription, factor, 'GATA-1,', probably, via, its, clustering, into, nuclear, foci])]). relacion([sujeto(['However,', 'G1HE', is, not, sufficient, to]), verbo([confer]), complemento([tissue, specificity, on, the, 'GATA-1', gene, in, 'vivo,', indicating, that, additional, regulatory, sequences, are, necessary])]). relacion([sujeto(['The', minigene]), verbo([activated]), complemento([the, transcription, of, a, reporter, gene, from, either, the, endogenous, or, an, exogenous, thymidine, kinase, 'promoter,', retaining, cell, 'type-specificity'])]). relacion([sujeto(['Moreover,', a, line, of, transgenic, mouse, that]), verbo([expressed]), complemento(['GATA-1', cDNA, under, the, control, of, the, complete, 979, bp, minigene, rescued, 'GATA-1', germ, line, mutant, mice, from, embryonic, lethality])]). relacion([sujeto(['Erythroid', and, megakaryocytic, lineage, differentiation, and, maturation, are]), verbo([regulated]), complemento([via, cooperation, between, transcription, factor, 'GATA1', and, its, essential, cofactor, 'friend-of-GATA1', '(', 'FOG1)'])]). relacion([sujeto(['The', interaction, between, these, two, murine, proteins, is, well, studied, in, vitro, and, depends, on, the]), verbo([binding]), complemento([of, 'Fog1', to, the, 'N-terminal', zinc, finger, '(', 'N-finger)', of, 'Gata1'])]). relacion([sujeto(['We', identified, the, human, 'FOG1', gene, on, chromosome, 16, q24, and]), verbo([found]), complemento([expression, mainly, in, hematopoietic, cells, and, also, in, several, other, tissues])]). relacion([sujeto(['Ex', vivo]), verbo([binding]), complemento([studies, demonstrated, that, 'FOG1', interacts, with, both, 'GATA1', and, 'GATA2'])]). relacion([sujeto(['We', and, others]), verbo([have]), complemento([described, patients, with, mutations, in, the, 'GATA1', 'N-finger', '(', 'V205', 'M,', 'D218G,', 'D218Y,', or, 'G208S),', who, suffer, from, macrothrombocytopenia, and, erythrocyte, abnormalities])]). relacion([sujeto(['Hydroxyurea', '(', 'HU)']), verbo([has]), complemento([been, shown, to, increase, the, proportion, of, fetal, haemoglobin, '(', 'HbF)', in, most, sickle, cell, patients])]). relacion([sujeto(['A', 'low-dosage', regimen]), verbo([increased]), complemento([total, haemoglobin, '(', 'Hb)', levels, in, some, thalassaemia, intermedia, patients, by, preferentially, increasing, 'beta-globin', biosynthesis])]). relacion([sujeto(['Low', doses, '(', from, 5, to, 25, micro, 'mol/l)']), verbo([increased]), complemento(['Hb', levels, by, up, to, 2.7, -, 'fold,', and, a, high, dose, '(', 100, micro, 'mol/l)', increased, 'Hb', levels, when, added, at, d, 3, -, 6, of, phase, 'II,', with, no, significant, changes, in, response, to, 'HU', during, the, late, stage, of, phase, 'II', culture, '(', &, 'gt;', or, =, 9, 'd)'])]). relacion([sujeto(['HU', exposure, during, d, 0, -, 3, of, phase, 'II', culture]), verbo([increased]), complemento([the, number, of, erythroid, colonies, to, a, maximum, of, fivefold, at, 5, micro, 'mol/l', 'HU'])]). relacion([sujeto(['Our', results]), verbo([suggest]), complemento([that, 'HU', exerts, 'concentration-dependent', effects, on, 'HbF', production, and, erythropoiesis, and, that, these, two, effects, are, mediated, by, distinct, molecular, mechanisms])]). relacion([sujeto(['Core-binding', factor, beta, '(', 'CBFbeta,', also, called, polyomavirus, enhancer]), verbo([binding]), complemento([protein, 2, beta, '(', 'PEBP2B))', is, associated, with, an, inversion, of, chromosome, 16, and, is, associated, with, acute, myeloid, leukemia, in, humans])]). relacion([sujeto(['CBFbeta', forms, a, heterodimer, with, 'RUNX1', '(', 'runt-related', transcription, factor, 1, ')', ',', which]), verbo([has]), complemento([a, 'DNA', binding, domain, homologous, to, the, 'pair-rule', protein, runt, in, 'Drosophila', melanogaster])]). relacion([sujeto(['Haploinsufficiency', of, another, 'runt-related', 'protein,', 'RUNX2', '(', also, called, 'CBFA1),']), verbo([causes]), complemento([cleidocranial, dysplasia, in, humans, and, is, essential, in, skeletal, development, by, regulating, osteoblast, differentiation, and, chondrocyte, maturation])]). relacion([sujeto(['Mice', deficient, in, 'Cbfb', '(', 'Cbfb(-/-))', die, at, 'midgestation,', so, the, function, of, 'Cbfbeta', in, skeletal, development]), verbo([has]), complemento([yet, to, be, ascertained])]). relacion([sujeto(['Electrophoretic', mobility, shift, assays, and, reporter, assays, showed, that, 'Cbfbeta', was, necessary, for, the, efficient, 'DNA']), verbo([binding]), complemento([of, 'Runx2', and, for, 'Runx2-dependent', transcriptional, activation])]). relacion([sujeto(['These', findings, indicate, that, 'Cbfbeta', is]), verbo([required]), complemento([for, the, function, of, 'Runx2', in, skeletal, development])]). relacion([sujeto(['Both', 'GATA-1', and, 'GATA-2', are]), verbo([regulated]), complemento([in, a, 'cell-type-specific', 'manner,', their, expression, being, strictly, controlled, during, the, development, and, differentiation, of, erythroid, cells])]). relacion([sujeto(['Closer', examination, revealed, a, 'cross-regulatory', mechanism, by, which, 'GATA-1', can, control, the, expression, of, 'GATA-2', and, vice, 'versa,', possibly, via, essential, 'GATA']), verbo([binding]), complemento([sites, in, their, 'cis-acting', elements])]). relacion([sujeto(['In', 'addition,', recent, studies, identified, several, human, inherited, hematopoietic, disorders, that, are]), verbo([caused]), complemento([by, mutations, in, 'cis-acting', 'GATA', binding, motifs, or, mutations, in, 'GATA-1', itself])]). relacion([sujeto(['The', expression, of, the, two, enzymes, is, differentially]), verbo([regulated]), complemento([in, various, 'cells,', but, little, is, known, about, the, regulatory, mechanisms])]). relacion([sujeto(['Whereas', phGPx, is]), verbo([expressed]), complemento([at, low, levels, in, many, 'organs,', snGPx, was, only, detected, in, 'testis,', 'kidney,', and, in, the, human, embryonic, kidney, cell, line, 'HEK293'])]). relacion([sujeto(['However,', it, strongly]), verbo([suppresses]), complemento([the, activity, of, the, 'ph/snGPx', promoter])]). relacion([sujeto(['These', data]), verbo([suggest]), complemento([negative, regulatory, elements, in, the, first, intron, of, the, 'ph/snGPx', 'gene,', and, 'DNase', protection, assays, revealed, the, existence, of, several, 'protein-binding', sites])]). relacion([sujeto(['The', corresponding, 'trans-regulatory', proteins, '(', 'SP1,', 'ERG1,', 'GATA1,', 'SREBP1,', 'USF1,', and, 'CREBP1)', were, 'identified,', and, in, vivo]), verbo([binding]), complemento([of, 'EGR1', and, 'SREBP1', was, shown, by, chromatin, immunoprecipitation])]). relacion([sujeto(['These', data, indicate, for, the, first, time, somatic, expression, of, the, snGPx, and]), verbo([provide]), complemento([evidence, for, the, existence, of, intronic, negative, 'cis-regulatory', elements, in, the, 'ph/snGPx', gene])]). relacion([sujeto(['Our', failure, to, detect, an, alternative, snGPx, promoter]), verbo([suggests]), complemento([that, transcription, of, the, 'ph/snGPx', gene, may, be, regulated, by, a, joint, basic, promoter])]). relacion([sujeto(['The', 'decision,', which, 'GPx', isoform, is]), verbo([expressed]), complemento([in, a, given, 'cell,', appears, to, be, made, by, alternative, splicing, of, a, joint, primary, transcript])]). relacion([sujeto(['To']), verbo([gain]), complemento([insights, into, the, molecular, basis, of, this, 'disease,', we, performed, gene, expression, profiling, of, 'CD34(+)', hematopoietic, progenitor, cells, from, 't-AML', patients])]). relacion([sujeto(['Our', analysis, revealed, that, there, are, distinct, subtypes, of, 't-AML', that]), verbo([have]), complemento([a, characteristic, gene, expression, pattern])]). relacion([sujeto(['Common', to, each, of, the, subgroups, are, gene, expression, patterns, typical, of]), verbo([arrested]), complemento([differentiation, in, early, progenitor, cells])]). relacion([sujeto(['Leukemias', with, a, -, 5, /, 'del(5q)']), verbo([have]), complemento([a, higher, expression, of, genes, involved, in, cell, cycle, control, '(', 'CCNA2,', 'CCNE2,', 'CDC2),', checkpoints, '(', 'BUB1),', or, growth, '(', 'MYC),', and, loss, of, expression, of, the, gene, encoding, 'IFN', consensus, 'sequence-binding', protein, '(', 'ICSBP)'])]). relacion([sujeto(['A', second, subgroup, of, 't-AML', is, characterized, by, 'down-regulation', of, transcription, factors]), verbo([involved]), complemento([in, early, hematopoiesis, '(', 'TAL1,', 'GATA1,', and, 'EKLF)', and, overexpression, of, proteins, involved, in, signaling, pathways, in, myeloid, cells, '(', 'FLT3)', and, cell, survival, '(', 'BCL2)'])]). relacion([sujeto(['Establishing', the, molecular, pathways]), verbo([involved]), complemento([in, 't-AML', may, facilitate, the, identification, of, selectively, expressed, genes, that, can, be, exploited, for, the, development, of, urgently, needed, targeted, therapies])]). relacion([sujeto(['The', recently, identified, zebrafish, 'T-box', gene, hrT, is]), verbo([expressed]), complemento([in, the, developing, heart, and, in, the, endothelial, cells, forming, the, dorsal, aorta])]). relacion([sujeto(['Orthologs', of, hrT, are]), verbo([expressed]), complemento([in, cardiovascular, cells, from, 'Drosophila', to, 'mouse,', suggesting, that, the, function, of, hrT, is, evolutionarily, conserved])]). relacion([sujeto(['The', role, of, hrT, in, cardiovascular, 'development,', 'however,']), verbo([has]), complemento([not, thus, far, been, determined, in, any, animal, model])]). relacion([sujeto(['Using', morpholino, antisense, 'oligonucleotides,', we, show, that, zebrafish, embryos, lacking, hrT, function]), verbo([have]), complemento([dysmorphic, hearts, and, an, absence, of, blood, circulation])]). relacion([sujeto(['In', 'particular,', we]), verbo([found]), complemento([that, the, loss, of, hrT, function, led, to, a, dramatic, upregulation, of, 'tbx5,', a, gene, required, for, normal, heart, morphogenesis])]). relacion([sujeto(['Conversely,', we, show, that, overexpression, of, hrT]), verbo([causes]), complemento([a, significant, downregulation, of, 'tbx5,', indicating, that, one, key, role, of, hrT, is, to, regulate, the, levels, of, tbx5])]). relacion([sujeto(['Secondly,', we]), verbo([found]), complemento([that, 'HrT', is, required, to, inhibit, the, expression, of, the, blood, lineage, markers, gata1, and, gata2, in, the, most, posterior, lateral, plate, mesoderm])]). relacion([sujeto(['Finally,', we, show, that, 'HrT', is]), verbo([required]), complemento([for, vasculogenesis, in, the, 'trunk,', leading, to, similar, vascular, defects, to, those, observed, in, midline, mutants, such, as, floating, head])]). relacion([sujeto(['Among', the, cell, lines, 'derived,', some, were, able, to, spontaneously, generate, adherent, 'stromal-like', cells, capable, of, taking, up, acetylated, 'low-density', 'lipoprotein,', and, they, could, be]), verbo([induced]), complemento([to, form, tubelike, structures, when, cultured, on, 'Matrigel'])]). relacion([sujeto(['They', also]), verbo([expressed]), complemento([the, transcription, factors, 'SCL,', 'GATA2,', 'GATA1,', 'PU'])]). relacion([sujeto(['Human', 'beta-globin', transgenes]), verbo([regulated]), complemento([by, the, locus, control, region, '(', 'LCR)', express, at, all, integration, sites, in, transgenic, mice])]). relacion([sujeto(['For', such, 'LCR', activity, at, ectopic, 'sites,', the, 5, '\'', 'HS3', element]), verbo([requires]), complemento([the, presence, of, the, 'AT-rich', region, '(', 'ATR)', in, 'beta-globin', 'intron-2'])]). relacion([sujeto(['Here,', we, examine, the, dependence, of, 5, '\'', 'HS3', 'LCR', activity, on, transcription, factor]), verbo([binding]), complemento([sites, in, the, 'ATR'])]). relacion([sujeto(['Transgenes', with, double, mutant, sites]), verbo([expressed]), complemento([at, all, sites, of, 'integration,', but, mean, expression, levels, in, transgenic, mice, were, reduced, from, 64, '%', per, copy, '(', 'BGT50)', to, 37, '%', '(', 'P', &, 'lt;'])]). relacion([sujeto(['We', conclude, that, the, ability, of, 5, '\'', 'HS3', to]), verbo([activate]), complemento([expression, from, all, transgene, integration, sites, is, dependent, on, sequences, in, the, 'ATR', that, are, not, bound, at, high, affinity, by, transcription, factors])]). relacion([sujeto(['In', 'addition,', the, 'Oct-1', site, in, the, 'ATR', is]), verbo([required]), complemento([for, 'high-level', 5, '\'', 'HS3', 'beta/gamma-globin', transgene, expression, and, should, be, retained, in, 'LCRbeta-globin', expression, cassettes, designed, for, gene, therapy])]). relacion([sujeto(['Vertebrate', hematopoiesis, is]), verbo([regulated]), complemento([by, distinct, 'cell-specific', transcription, factors, such, as, 'GATA-1', and, 'SCL'])]). relacion([sujeto(['Mammalian', 'p45-NFE2', was, characterized, for, its, ability, to]), verbo([bind]), complemento([the, hypersensitive, sites, of, the, globin, locus, control, region])]). relacion([sujeto(['NFE2', is, a, member, of, a, 'cap\'n\'collar', '(', 'CNC)', and, basic, zipper, '(', 'BZIP)', superfamily, that]), verbo([regulates]), complemento([gene, transcription])]). relacion([sujeto(['It']), verbo([has]), complemento([been, implicated, in, diverse, processes, such, as, globin, gene, 'expression,', oxidative, 'stress,', and, platelet, lineage, differentiation])]). relacion([sujeto(['Here,', we]), verbo([have]), complemento([isolated, the, zebrafish, ortholog, of, 'NFE2'])]). relacion([sujeto(['Mapping', the, zebrafish, 'NFE2', to, linkage, group, 23, establishes, a, region, of, chromosomal, synteny, with, human, chromosome, 12, ',', further]), verbo([suggesting]), complemento([evolutionary, conservation])]). relacion([sujeto(['During', 'embryogenesis,', the, zebrafish, gene, is]), verbo([expressed]), complemento([specifically, in, erythroid, cells, and, also, in, the, developing, ear])]). relacion([sujeto(['NFE2', expression, is, lacking, in, zebrafish, mutants, that]), verbo([have]), complemento([no, hematopoietic, cells])]). relacion([sujeto(['An', analysis, of, the, sauternes, 'mutant,', which, carries, a, mutation, in, the, 'ALAS-2', gene, and, thus]), verbo([has]), complemento([defective, heme, 'synthesis,', demonstrates, higher, levels, of, 'NFE2', expression, than, normal])]). relacion([sujeto(['Posttranslational', modification, of, histones, through, 'acetylation,', 'methylation,', and, phosphorylation, is, a, common, mode, of]), verbo([regulating]), complemento([chromatin, structure, 'and,', 'therefore,', diverse, nuclear, processes])]). relacion([sujeto(['Whereas', activators, directly]), verbo([recruit]), complemento(['acetyltransferases,', the, process, whereby, 'H3-meK4', is, established, is, unknown])]). relacion([sujeto(['We', tested, whether, the, 'hematopoietic-specific', activators, 'NF-E2', and, 'GATA-1,', which]), verbo([mediate]), complemento([transactivation, of, the, 'beta-globin', 'genes,', induce, both, histone, acetylation, and, 'H3-meK4'])]). relacion([sujeto(['Through', the, use, of, 'NF-E2-', and, 'GATA-1-null', cell, 'lines,', we, show, that, both, activators]), verbo([induce]), complemento(['H3', acetylation, at, the, promoter, upon, transcriptional, activation])]). relacion([sujeto(['However,', analysis, of, 'H3-mek4', revealed, that, 'NF-E2', and, 'GATA-1', differentially]), verbo([regulate]), complemento([chromatin, modifications, at, the, betamajor, promoter])]). relacion([sujeto(['NF-E2,', but, not, 'GATA-1,']), verbo([induces]), complemento(['H3-meK4', at, the, promoter])]). relacion([sujeto(['Thus,', under, conditions, in, which, 'NF-E2', and, 'GATA-1']), verbo([activate]), complemento([the, transcription, of, an, endogenous, gene, at, least, 570, -, 'fold,', these, activators, differ, in, their, capacity, to, induce, 'H3-meK4'])]). relacion([sujeto(['Despite', strong, 'H3-meK4', at, hypersensitive, site, 2, of, the, upstream, locus, control, 'region,', neither, factor, was]), verbo([required]), complemento([to, establish, 'H3-meK4', at, this, site])]). relacion([sujeto(['As', 'GATA-1']), verbo([induced]), complemento(['H3', 'acetylation,', but, not, 'H3-meK4,', at, the, 'promoter,', 'H3', acetylation, and, 'H3-meK4', components, of, a, composite, histone, modification, pattern, can, be, established, independently])]). relacion([sujeto(['Platelet', glycoprotein, 'VI', is, a, collagen, receptor, belonging, to, the, 'immunoglobulin-like', protein, family, that, is, essential, for, platelet, interactions, with, collagen, and, is, exclusively]), verbo([expressed]), complemento([in, the, megakaryocytic, lineage])]). relacion([sujeto(['We', next, subcloned, the, 5, '\'', regulatory, region, of, 'GP6', into, 'pGL3-basic', '[', 'pGL3(-1576)]', and, used, deletion, mutagenesis, to, identify, important, regulatory, 'regions,', comparing, the, activity, of, transiently]), verbo([expressed]), complemento(['promoter-luciferase', constructs, in, 'Dami', and, 'HeLa', cells])]). relacion([sujeto(['We']), verbo([found]), complemento([that, megakaryocyte, 'lineage-specific', transcription, is, largely, controlled, within, the, segment, -, 191, /, -, 39])]). relacion([sujeto(['We']), verbo([have]), complemento([determined, that, the, 'GP6', sequence, -, 191, to, -, 39, represents, the, core, promoter, and, that, transcription, is, driven, largely, by, 'GATA-1', '(', -, 176, ')', and, 'c-Ets-1', '(', -, 45, ')', sites, within, this, segment])]). relacion([sujeto(['The', platelet, collagen, receptor, glycoprotein, '(', 'GP)(1)', 'VI', plays, a, crucial, role, in, platelet, activation, and, thrombus, formation, and]), verbo([decreased]), complemento([levels, or, defective, 'GPVI', may, lead, to, excessive, bleeding])]). relacion([sujeto(['In', this, study, we, investigate, the, regulation, of, 'GPVI', expression, and, show, that, thrombopoietin]), verbo([induces]), complemento([its, expression, in, the, megakaryocytic, cell, line, 'UT-7/TPO'])]). relacion([sujeto(['A', 5, '\'', -, region, flanking, the, transcription, start, point, of, the, 'GPVI', gene, was, cloned, '(', -, 694, to, +, 29, ')', and, we]), verbo([report]), complemento([that, this, putative, 'GPVI', promoter, bestows, 'megakaryocye-specific', expression])]). relacion([sujeto(['We', show, that, transcription, factors, 'GATA-1,', 'Fli-1,', and, 'Sp1', can]), verbo([bind]), complemento([to, and, activate, this, promoter])]). relacion([sujeto(['Finally,', 'GPVI', mRNA, was, detected, only, in, megakaryocytic, cell, lines]), verbo([expressing]), complemento([both, 'Fli-1', and, 'GATA-1,', and, we, show, that, overexpression, of, 'Fli-1', in, a, stable, cell, line, '(', which, expresses, endogenous, 'GATA-1', and, 'Sp1)', results, in, expression, of, the, endogenous, 'GPVI', gene])]). relacion([sujeto(['FOG-1', can]), verbo([stimulate]), complemento([or, inhibit, 'GATA-1', activity, depending, on, cell, and, promoter, context])]). relacion([sujeto(['FOG-1']), verbo([stimulates]), complemento(['GATA-1-dependent', alphaIIb, gene, expression, in, a, manner, that, requires, their, direct, physical, interaction])]). relacion([sujeto(['Transcriptional', output, by, the, 'GATA-1-FOG-1', complex, is, determined, by, the, hematopoietic, 'Ets', protein, 'Fli-1', that]), verbo([binds]), complemento([to, an, adjacent, 'Ets', element])]). relacion([sujeto(['We', investigated, the, expression, of, the, 'PLZF', gene, in, purified, human, hematopoietic, progenitors]), verbo([induced]), complemento([to, unilineage, 'erythroid,', granulocytic, or, megakaryocytic, differentiation, and, maturation, in, 'serum-free', culture])]). relacion([sujeto(['PLZF', is]), verbo([expressed]), complemento([in, quiescent, 'progenitors:', the, expression, level, progressively, rises, through, megakaryocytic, 'development,', whereas, it, gradually, declines, in, erythroid, and, granulopoietic, culture])]). relacion([sujeto(['PLZF', overexpression, upmodulates, the, megakaryocytic, specific, markers, '(', 'CD42a,', 'CD42b,', 'CD61,', 'PF4)', and]), verbo([induces]), complemento([the, thrombopoietin, receptor, '(', 'TpoR)'])]). relacion([sujeto(['The', proximal, promoter, of, the, 'TpoR', gene, is]), verbo([activated]), complemento([in, 'PLZF-expressing', 'TF1', 'cells:', in, this, promoter, 'region,', a, 'PLZF', 'DNA-binding', site, was, identified, by, deletion, constructs, studies])]). relacion([sujeto(['Interestingly,', 'PLZF', and, 'GATA1', proteins, coimmunoprecipitate, in, 'PLZF-expressing', 'TF1', 'cells:', enforced, expression, of, both, 'PLZF', and, 'GATA1', in, 'TF1', cells, results, in]), verbo([increased]), complemento([upregulation, of, megakaryocytic, 'markers,', as, compared, to, exogenous, 'PLZF', or, 'GATA1', 'alone,', suggesting, a, functional, role, for, the, 'PLZF/GATA1', complex])]). relacion([sujeto(['Our', data, indicate, that, 'PLZF', plays, a, significant, stimulatory, role, in, megakaryocytic, 'development,', seemingly]), verbo([mediated]), complemento([in, part, by, induction, of, 'TpoR', expression, at, transcriptional, level])]). relacion([sujeto(['The', transcription, factors, 'GATA-1', and, 'GATA-4']), verbo([have]), complemento([been, implicated, in, the, regulation, of, testicular, development, and, function])]). relacion([sujeto(['Their', cofactors, 'FOG-1', and, 'FOG-2', are]), verbo([expressed]), complemento([in, the, 'gonads,', but, their, 'cell-specific', and, developmental, expression, in, the, testis, remains, unresolved])]). relacion([sujeto(['GATA-4', and, 'FOG-2,', but, not, 'GATA-1', or, 'FOG-1,', were]), verbo([expressed]), complemento([as, early, as, in, the, male, urogenital, ridge])]). relacion([sujeto(['FOG-1', was]), verbo([expressed]), complemento([from, 'E15'])]). relacion([sujeto(['In', the, postnatal, 'testis,', 'FOG-2', was, abundantly]), verbo([expressed]), complemento([immediately, after, 'birth,', but, in, adult, testis, its, expression, was, predominantly, restricted, to, stage, 'VII-XII', seminiferous, tubules])]). relacion([sujeto(['Stage', specificity, was, also]), verbo([found]), complemento([for, 'FOG-1,', 'which,', similarly, to, 'GATA-1,', was, abundantly, expressed, in, stage, 'VII-XII', tubules, during, adulthood])]). relacion([sujeto(['Our', results, indicate, that, 'FOG-2,', in, addition, to, 'GATA-4,']), verbo([has]), complemento([a, role, in, early, gonadal, development, and, sexual, 'differentiation,', and, 'FOG-1', at, later, fetal, 'stages,', while, 'GATA-1', executes, its, action, postnatally])]). relacion([sujeto(['The', findings]), verbo([suggest]), complemento(['that,', in, contrast, to, the, hematopoietic, system, and, the, 'heart,', 'GATA-1', and, 'GATA-4', do, not, use, 'FOG-1', and, 'FOG-2', respectively, as, their, only, cofactors, during, the, early, stages, of, testicular, development])]). relacion([sujeto([1]), verbo([have]), complemento([been, reported, to, functionally, antagonize, one, another, in, the, regulation, of, erythroid, versus, myeloid, gene, transcription, and, development])]). relacion([sujeto(['The', 'CCAAT', enhancer]), verbo([binding]), complemento([protein, epsilon, '(', 'C/EBPepsilon)', is, expressed, as, multiple, isoforms, and, has, been, shown, to, be, essential, to, myeloid, '(', 'granulocyte)', terminal, differentiation])]). relacion([sujeto(['We']), verbo([have]), complemento([defined, a, novel, 'synergistic,', as, opposed, to, 'antagonistic,', combinatorial, interaction, between, 'GATA-1', and, 'PU'])]). relacion([sujeto([1, consensus, sites, that]), verbo([bind]), complemento([these, factors, in, nuclear, extracts, of, the, eosinophil, myelocyte, cell, 'line,', 'AML14'])]). relacion([sujeto([1, 'synergy,', and, repressor, activity, of, 'C/EBPepsilon(27)', are]), verbo([mediated]), complemento([via, 'protein-protein', interactions, through, the, 'C/EBP', 'and/or', 'GATA-binding', sites, but, not, the, 'PU'])]). relacion([sujeto([3, 'D10', eosinophils, show, that, both, 'C/EBPepsilon(32/30)', and, 'epsilon(27)', physically]), verbo([interact]), complemento([in, vivo, with, 'PU'])]). relacion([sujeto(['The', 'N', finger]), verbo([mediates]), complemento([interaction, with, 'FOG-1,', a, cofactor, for, 'GATA-1,', and, also, modulates, 'DNA-binding', 'affinity,', notably, at, complex, or, palindromic, 'GATA', sites])]). relacion([sujeto(['Strong', sequence, conservation, of, residues, facing, 'DNA']), verbo([suggests]), complemento([that, this, other, surface, may, also, have, an, important, role])]). relacion([sujeto(['We']), verbo([report]), complemento([here, that, a, syndrome, of, 'X-linked', thrombocytopenia, with, thalassemia, in, humans, is, caused, by, a, missense, mutation, '(', 'Arg216Gln)', in, the, 'GATA-1', 'N', finger])]). relacion([sujeto(['Compared', with, 'wild-type', 'GATA-1,', 'Arg216Gln', 'GATA-1', shows, comparable, affinity, to, single, 'GATA', sites, but]), verbo([decreased]), complemento([affinity, to, palindromic, sites])]). relacion([sujeto(['Arg216Gln', 'GATA-1']), verbo([interacts]), complemento([with, 'FOG-1', similarly, with, 'wild-type', 'GATA-1'])]). relacion([sujeto(['Together,', these, findings]), verbo([suggest]), complemento([that, residues, of, the, 'N', finger, of, 'GATA-1-facing', 'DNA', contribute, to, 'GATA-1', function, apart, from, interaction, with, the, cofactor, 'FOG-1'])]). relacion([sujeto(['This', is, also, the, first, example, of, 'beta-thalassemia', in, humans]), verbo([caused]), complemento([by, a, mutation, in, an, erythroid, transcription, factor])]). relacion([sujeto(['alpha-Spectrin', is, a, highly]), verbo([expressed]), complemento([membrane, protein, critical, for, the, flexibility, and, stability, of, the, erythrocyte])]). relacion([sujeto(['Using', transfection, of, 'promoter/reporter', plasmids, in, human, tissue, culture, cell, 'lines,', in, vitro, 'DNase', 'I', footprinting, 'analyses,', and, gel, mobility, shift, 'assays,', an, 'alpha-spectrin', gene, erythroid, promoter, with]), verbo([binding]), complemento([sites, for, 'GATA-1-', and, 'NF-E2-related', proteins, was, identified])]). relacion([sujeto(['Both']), verbo([binding]), complemento([sites, were, required, for, full, promoter, activity])]). relacion([sujeto(['In', transgenic, 'mice,', a, reporter, gene, directed, by, the, 'alpha-spectrin', promoter, was]), verbo([expressed]), complemento([in, yolk, 'sac,', fetal, 'liver,', and, erythroid, cells, of, bone, marrow, but, not, adult, reticulocytes])]). relacion([sujeto(['Targeted', disruption, of, vascular, endothelial, growth, factor, '(', 'VEGF)', or, its, receptor, kdr, '(', 'flk1,', 'VEGFR2)', in, mouse, embryos, results, in, a, severe, reduction, of, all, blood, 'vessels,', while, the, complete]), verbo([loss]), complemento([of, flt1, '(', 'VEGFR1)', leads, to, an, increased, number, of, hemangioblasts, and, a, disorganized, vasculature])]). relacion([sujeto(['Analysis', of, mRNA, expression, in, flk1, mutant, embryos, showed, that, flk1, expression, was, severely, 'downregulated,', while, the, expression, of, other, genes, '(', 'scl,', 'gata1,', and, 'fli1)']), verbo([involved]), complemento([in, vasculogenesis, or, hematopoiesis, was, unchanged])]). relacion([sujeto(['Overexpression', of, 'vegf(121+165)']), verbo([led]), complemento([to, the, formation, of, additional, vessels, only, in, sibling, 'larvae,', not, in, flk1, mutants])]). relacion([sujeto(['We', demonstrate, that, flk1, is, not]), verbo([required]), complemento([for, proper, vasculogenesis, and, hematopoiesis, in, zebrafish, embryos])]). relacion([sujeto(['The', hematopoietic, transcription, factor, 'GATA-1']), verbo([regulates]), complemento([erythropoiesis, and, 'beta-globin', expression])]). relacion([sujeto(['Although', consensus, 'GATA-1']), verbo([binding]), complemento([sites, exist, throughout, the, murine, 'beta-globin', 'locus,', we, found, that, 'GATA-1', discriminates, among, these, sites, in, vivo])]). relacion([sujeto(['GATA-1']), verbo([induced]), complemento(['RNA', polymerase, 'II', '(', pol, 'II)', recruitment, to, subregions, of, the, locus, control, region, and, to, the, 'beta-globin', promoters])]). relacion([sujeto(['The', hematopoietic, factor, 'NF-E2', cooperated, with, 'GATA-1', to]), verbo([recruit]), complemento([pol, 'II', to, the, promoters])]). relacion([sujeto(['Children', with, 'Down', syndrome]), verbo([have]), complemento([a, 10, -, 20, -, fold, elevated, risk, of, developing, 'leukemia,', particularly, acute, megakaryoblastic, leukemia, '(', 'AMKL)'])]). relacion([sujeto(['While', a, subset, of, pediatric, 'AMKLs', is]), verbo([associated]), complemento([with, the, 1, ;, 22, translocation, and, expression, of, a, mutant, fusion, 'protein,', the, genetic, alterations, that, promote, 'Down', 'syndrome-related', 'AMKL', '(', 'DS-AMKL)', have, remained, elusive])]). relacion([sujeto(['Here', we, show, that, leukemic, cells, from, every, individual, with, 'DS-AMKL', that, we, examined, contain, mutations, in, 'GATA1,', encoding, the, essential, hematopoietic, transcription, factor, 'GATA1', '(', 'GATA']), verbo([binding]), complemento([protein, 1, or, globin, transcription, factor, 1, ')'])]). relacion([sujeto(['These', mutations]), verbo([prevent]), complemento([synthesis, of, 'full-length', 'GATA1,', but, not, synthesis, of, a, shorter, variant, that, is, initiated, downstream])]). relacion([sujeto(['We', show, that, the, shorter, 'GATA1', 'protein,', which, lacks, the, 'N-terminal', activation, 'domain,']), verbo([binds]), complemento(['DNA', and, interacts, with, its, essential, cofactor, 'Friend', of, 'GATA1', '(', 'FOG1;', encoded, by, 'ZFPM1)', to, the, same, extent, as, does, 'full-length', 'GATA1,', but, has, a, reduced, transactivation, potential])]). relacion([sujeto(['Although', some]), verbo([reports]), complemento([suggest, that, the, activation, domain, is, dispensable, in, 'cell-culture', models, of, 'hematopoiesis,', one, study, has, shown, that, it, is, required, for, normal, development, in, vivo])]). relacion([sujeto(['Together,', these, findings, indicate, that]), verbo([loss]), complemento([of, wildtype, 'GATA1', constitutes, one, step, in, the, pathogenesis, of, 'AMKL', in, 'Down', syndrome])]). relacion([sujeto(['The', phenotype]), verbo([induced]), complemento([by, the, 'GATA-1(low)', '(', 'neodeltaHS)', mutation, is, here, further, characterized, by, analyzing, the, hemopoietic, system, during, the, aging, '(', up, to, 20, 'months)', of, a, 'GATA-1(low)', colony, '(', 135, mutants, and, 40, normal, 'littermates)'])]). relacion([sujeto(['Mutants']), verbo([expressed]), complemento([normal, hematocrit, values, '(', 'Hct', =, 45.9, +, /, -, 4.0, ')', until, 12, months, but, became, anemic, from, 15, months, on, '(', 'Hct', =, 30.9, +, /, -, 3.9, ;, 'P', &, 'lt;'])]). relacion([sujeto(['Anemia', was]), verbo([associated]), complemento([with, several, markers, of, myelofibrosis, such, as, the, presence, of, 'tear-drop', poikilocytes, and, progenitor, cells, in, the, 'blood,', collagen, fibers, in, the, marrow, and, in, the, 'spleen,', and, hemopoietic, foci, in, the, liver])]). relacion([sujeto(['Semiquantitative', reverse, 'transcription-polymerase', chain, reaction, showed, that, growth, factor, genes, implicated, in, the, development, of, myelofibrosis, '(', such, as, 'osteocalcin,', transforming, growth, 'factor-beta1,', 'platelet-derived', growth, 'factor,', and, vascular, endothelial, growth, 'factor)', were, all]), verbo([expressed]), complemento([in, the, marrow, from, the, mutants, at, higher, levels, than, in, corresponding, normal, tissues])]). relacion([sujeto(['Previous', studies]), verbo([have]), complemento([established, that, protein, kinase, 'C-zeta', '(', 'PKC-zeta)', is, critical, for, neuronal, cell, differentiation])]). relacion([sujeto(['In', this, 'study,', we]), verbo([have]), complemento([investigated, the, influence, of, 'PKC-zeta', overexpression, on, the, phenotype, of, the, human, monocytic, 'U937', leukaemic, cells])]). relacion([sujeto(['PKC-zeta-overexpressing', 'U937', cells, exhibited, an, erythroid, phenotype, characterized, by, high, levels, of, glycophorin, 'A,', cell, 'haemoglobinization,']), verbo([increased]), complemento(['GATA-1', transcripts, and, protein, 'expression,', compared, with, controls])]). relacion([sujeto(['Immunoprecipitation', studies, revealed, that, 'GATA-1', protein, was, constitutively]), verbo([phosphorylated]), complemento([in, 'PKC-zeta-overexpressing', cells])]). relacion([sujeto(['Moreover,', 'GATA-1', did, not]), verbo([interact]), complemento([with, 'PKC-zeta', but, interacted, with, 'ERK1,', which, was, constitutively, activated, and, accumulated, in, the, nucleus, of, 'U937', zetaJ])]). relacion([sujeto(['Collectively,', these, results]), verbo([suggest]), complemento([a, model, in, which, 'PKC-zeta', induces, 'MEK-dependent', 'ERK1', 'activation,', 'ERK1', translocation, to, the, 'nucleus,', 'GATA-1/ERK1', interaction, and, 'ERK1-independent', 'GATA-1', phosphorylation, resulting, in, 'GATA-1', accumulation])]). relacion([sujeto(['To', 'conclude,', this, study]), verbo([provides]), complemento([evidence, for, the, role, of, 'PKC-zeta', in, erythroid, gene, regulation])]). relacion([sujeto(['Molecular', chaperones, that]), verbo([regulate]), complemento([globin, subunit, 'stability,', folding, or, assembly, have, been, proposed, to, exist, but, have, never, been, identified])]). relacion([sujeto(['Here', we, identify, a, protein, stabilizing, free, 'alpha-haemoglobin', by, using, a, screen, for, genes]), verbo([induced]), complemento([by, the, essential, erythroid, transcription, factor, 'GATA-1', '(', refs, 4, ',', 5, ')'])]). relacion([sujeto(['Hence,', 'AHSP', is]), verbo([required]), complemento([for, normal, 'erythropoiesis,', probably, acting, to, block, the, deleterious, effects, of, free, 'alpha-haemoglobin', precipitation])]). relacion([sujeto(['Accordingly,', 'AHSP', gene, dosage, is, predicted, to]), verbo([modulate]), complemento([pathological, states, of, 'alpha-haemoglobin', 'excess,', such, as, 'beta-thalassaemia'])]). relacion([sujeto(['GATA-1', is, essential, for, maturation, of, erythroid, and, megakaryocytic, 'precursors,', as, revealed, by, gene]), verbo([targeting]), complemento([in, mice])]). relacion([sujeto(['Here', we, demonstrate, that, deletion, of, a, 'high-affinity', 'GATA-binding', site, in, the, 'GATA-1', 'promoter,', an, element, presumed, to]), verbo([mediate]), complemento([positive, autoregulation, of, 'GATA-1', 'expression,', leads, to, selective, loss, of, the, eosinophil, lineage])]). relacion([sujeto(['These', findings]), verbo([suggest]), complemento([that, 'GATA-1', is, required, for, specification, of, this, lineage, during, hematopoietic, development])]). relacion([sujeto(['A', high, level, of, 'GATA-1', and, 'GATA-2', expression]), verbo([has]), complemento([been, observed, in, 'eosinophils,', but, their, roles, in, eosinophil, development, remain, uncertain, both, in, vitro, and, in, vivo])]). relacion([sujeto(['Expression', of, 'GATA-1', exclusively]), verbo([promotes]), complemento([development, and, terminal, maturation, of, eosinophils])]). relacion([sujeto(['GATA-1', and, 'GATA-2', could, be, novel, molecular]), verbo([targets]), complemento([for, therapeutic, approaches, to, allergic, inflammation])]). relacion([sujeto(['Previous', work]), verbo([has]), complemento([demonstrated, that, 'lineage-specific', transcription, factors, play, essential, roles, in, red, blood, cell, development])]). relacion([sujeto(['More', recent, studies]), verbo([have]), complemento([shown, that, these, factors, participate, in, critical, 'protein-protein', interactions, in, addition, to, binding, 'DNA'])]). relacion([sujeto(['The', zinc, finger, transcription, factor, 'GATA-1,', a, central, mediator, of, erythroid, gene, 'expression,']), verbo([interacts]), complemento([with, multiple, proteins, including, 'FOG-1,', 'EKLF,', 'SP1,', 'CBP/p300', and, 'PU'])]). relacion([sujeto(['However,', several, new, findings]), verbo([have]), complemento([provided, further, insight, into, the, functional, significance, of, some, of, these, interactions])]). relacion([sujeto(['Studies']), verbo([involving]), complemento([point, mutants, of, 'GATA-1', have, shown, that, a, direct, physical, interaction, between, 'GATA-1', and, 'FOG-1', is, essential, for, normal, human, erythroid, and, megakaryocyte, maturation, in, vivo])]). relacion([sujeto(['In', 'addition,', evidence]), verbo([has]), complemento([emerged, that, physical, interaction, between, 'GATA-1', and, the, 'myeloid/lymphoid', specific, factor, 'PU'])]). relacion([sujeto([1, ',', an, oncogene, implicated, in, murine, 'erythroleukemia,']), verbo([acts]), complemento([to, functionally, 'cross-antagonize', one, another])]). relacion([sujeto(['This']), verbo([provides]), complemento([a, possible, mechanism, by, which, dysregulated, expression, of, hematopoietic, transcription, factors, leads, to, lineage, maturation, arrest, in, leukemias])]). relacion([sujeto(['FOG-1,', like, its]), verbo([interacting]), complemento([partner, 'GATA-1,', is, required, for, normal, differentiation, of, erythroid, and, megakaryocytic, cells])]). relacion([sujeto(['Here,', we]), verbo([have]), complemento([developed, a, functional, assay, for, 'FOG-1', based, on, its, ability, to, rescue, erythroid, and, megakaryocytic, maturation, of, a, genetically, engineered, 'FOG-1(-/-)', cell, line])]). relacion([sujeto(['We', demonstrate, that, interaction, through, only, one, of, 'FOG-1\'s', four, 'GATA-binding', zinc, fingers, is, sufficient, for, 'rescue,']), verbo([providing]), complemento([evidence, against, a, model, in, which, 'FOG-1', acts, to, bridge, multiple, 'GATA-binding', 'DNA', elements])]). relacion([sujeto(['Importantly,', we]), verbo([find]), complemento([that, distinct, regions, of, 'FOG-1', differentially, influence, erythroid, versus, megakaryocyte, maturation])]). relacion([sujeto(['As', 'such,', we, propose, that, 'FOG-1', may]), verbo([modulate]), complemento([the, fate, of, a, bipotential, 'erythroid/megakaryocytic', precursor, cell])]). relacion([sujeto(['In', this, 'study,', we, demonstrated, that, 'E4bp4', is]), verbo([regulated]), complemento([by, 'IL-3', mainly, at, the, transcriptional, level])]). relacion([sujeto(['Gel', shift, assays, demonstrated, that, both, 'GATA-1', and, 'GATA-2', proteins]), verbo([bind]), complemento([to, the, 'E4bp4', 'GATA', site, in, 'vitro,', and, the, chromatin, immunoprecipitation, assay, further, confirmed, the, in, vivo, binding, of, 'GATA-1', to, the, 'E4bp4', promoter])]). relacion([sujeto(['Last,', we, demonstrated, that, alteration, of, 'GATA-1']), verbo([binding]), complemento([to, the, 'GATA', site, by, stably, overexpressing, 'GATA-1', or, a, 'GATA-1', mutant, containing, only, the, 'DNA-binding', domain, not, only, modulates, the, expression, of, the, 'E4bp4', gene, but, also, influences, apoptosis, induced, by, 'IL-3', removal])]). relacion([sujeto(['Taken', 'together,', our, results]), verbo([suggest]), complemento([that, the, 'GATA', factors, play, an, important, role, in, transducing, the, survival, signal, of, 'IL-3,', and, one, of, their, cellular, targets, is, 'E4bp4'])]). relacion([sujeto(['It']), verbo([has]), complemento([been, reported, in, transgenic, experiments, that, 'HS3', preferentially, regulates, 'epsilon-globin', gene, expression])]). relacion([sujeto(['In', order, to, elucidate, the, regulatory, function, of, 'HS3', in, the, expression, of, globin, 'gene,']), verbo([nuclear]), complemento([extracts, from, mouse, hematopoietic, tissues, at, several, developmental, stages, were, prepared, and, the, binding, of, the, nuclear, factors, to, 'HS3', was, analysed, by, using, electrophoresis, mobility, shift, 'assay(EMSA)'])]). relacion([sujeto(['Our', results, showed, that, the]), verbo([binding]), complemento([patterns, of, 'HS3', with, nuclear, extracts, of, mouse, hematopoietic, tissues, at, day, 13, and, day, 18, of, gestation, were, completely, 'different;', 'furthermore,', by, 'Southwestern', 'Blot,', the, distinction, between, both, stages, was, also, demonstrated])]). relacion([sujeto(['It']), verbo([has]), complemento([been, known, that, 'GATA', and, 'CACCC', binding, motifs, are, contained, within, 'HS3', core, region])]). relacion([sujeto(['Using', competitive, 'gel-retardation', 'assay,', we]), verbo([found]), complemento([that, no, shift, bands, could, be, competed, by, using, 'CACCC', motif, as, a, competitor])]). relacion([sujeto(['We']), verbo([suggested]), complemento([that, the, shift, 'bands,', which, could, not, be, competed, by, both, 'motifs,', might, be, novel, and, 'stage-specific', factors])]). relacion([sujeto(['In', 'addition,', by, using, 'Western', 'Blot,', we, demonstrated, that, the, two, shift, bands, at, day, 13, and, day, 18, of, 'gestation,', competed, by, 'GATA', 'motif,', were, 'GATA-2', and, 'GATA-1', 'respectively:', 'GATA-1', was]), verbo([expressed]), complemento([in, mouse, hematopoietic, tissues, at, day, 18, of, gestation, and, not, expressed, at, day, 13, of, 'gestation;', 'however,', 'GATA-2', was, only, expressed, in, mouse, hematopoietic, tissues, at, day, 13, of, gestation])]). relacion([sujeto(['According', to, these, 'results,', we, speculated, that, 'HS3', might, play, an, important, role, in, regulation, of, 'stage-specific', expression, of, globin, genes, through, interaction, between, 'stage-specific']), verbo([nuclear]), complemento([factors, and, 'HS3'])]). relacion([sujeto([1]), verbo([inhibits]), complemento([erythroid, cell, differentiation, and, contributes, to, the, formation, of, murine, erythroleukemias, '(', 'MEL)'])]). relacion([sujeto([1, specifically, and, efficiently]), verbo([inhibits]), complemento(['CBP-mediated', acetylation, of, several, nuclear, 'proteins,', including, the, hematopoietic, transcription, factors, 'GATA-1,', 'NF-E2,', and, erythroid, 'Krüppel-like', factor])]). relacion([sujeto(['CBP', acetyltransferase, activity]), verbo([increases]), complemento([during, 'MEL', cell, differentiation, as, 'PU'])]). relacion([sujeto([1, levels, decline, and, is]), verbo([inhibited]), complemento([by, sustained, 'PU'])]). relacion([sujeto([1]), verbo([inhibits]), complemento([the, 'differentiation-associated', increase, in, histone, acetylation, at, an, 'erythroid-specific', gene, locus, in, vivo])]). relacion([sujeto(['Together,', these, findings]), verbo([suggest]), complemento([that, aberrant, expression, of, 'PU'])]). relacion([sujeto([1, and, possibly, other, members, of, the, 'Ets', family, of, oncoproteins, subverts, normal, cellular, differentiation, in, part, by]), verbo([inhibiting]), complemento([the, acetylation, of, critical, nuclear, factors, involved, in, balancing, cellular, proliferation, and, maturation])]). relacion([sujeto([1]), verbo([bound]), complemento([to, the, region, close, to, that, recognized, by, 'Elf-1'])]). relacion([sujeto(['The', 'alpha-chain', promoter, activity, was, 'up-regulated', approximately, 2, -, fold, by, exogenously]), verbo([expressed]), complemento(['YY1', or, 'PU'])]). relacion([sujeto([1, or, 'YY1', dramatically]), verbo([activated]), complemento([the, promoter, approximately, 41, -, or, approximately, 27, -, 'fold,', respectively])]). relacion([sujeto([1, was, 'surprising,', because, these, transcription, factors, are, known, to]), verbo([inhibit]), complemento([the, respective, transactivating, activities, of, each, other])]). relacion([sujeto([1, and, 'YY1', with, 'GATA-1', were]), verbo([inhibited]), complemento([by, overexpression, of, 'Elf-1,', indicating, that, 'Elf-1', serves, as, a, repressor, for, the, 'alpha-chain', gene, expression])]). relacion([sujeto(['The', signal, transducer, and, activator, of, transcription, 3, '(', 'Stat3),', a, member, of, the, 'Stat', family, of, 'proteins,', is, commonly]), verbo([activated]), complemento([by, thrombopoietic, cytokines, including, thrombopoietin, '(', 'TPO),', interleukin, '(', 'IL)-6,', and, 'interleukin-11'])]). relacion([sujeto(['This']), verbo([finding]), complemento([strongly, suggested, that, 'Stat3', has, an, important, role, in, megakaryopoiesis, and, thrombopoiesis])]). relacion([sujeto(['To', clarify, the, functional, role, of, 'Stat3', in, in, vivo, megakaryopoiesis, and, 'thrombopoiesis,', we, generated, transgenic, mice, overexpressing, a, 'dominant-negative', 'Stat3,', 'Stat3F,', to]), verbo([suppress]), complemento([the, function, of, endogenous, 'Stat3'])]). relacion([sujeto(['To', accomplish, the, selective, expression, of, 'Stat3F', in, megakaryocytic, lineage, 'cells,', we, used, the, regulatory, gene, region, of, 'GATA-1', transcription, factor, selectively]), verbo([expressed]), complemento([in, megakaryocytic, and, erythroid, lineage, cells])]). relacion([sujeto(['It', was, confirmed, by, 'Western', blotting, analysis, that, 'Stat3F', proteins, were, highly]), verbo([expressed]), complemento([in, the, platelets, from, the, 'Tg', mice])]). relacion([sujeto(['In', 'addition,', it, was]), verbo([found]), complemento([that, 'Stat3', activation, induced, by, 'TPO', stimulation, was, drastically, suppressed, in, these, 'Tg', mice, compared, with, littermates])]). relacion([sujeto(['Platelet', counts, were, within, the, normal, range, in, 'steady-state', conditions, and, were, recovered, normally, from, transient, thrombocytopenia]), verbo([induced]), complemento([by, antiplatelet, serum, injection])]). relacion([sujeto(['Collectively,', our, results, strongly]), verbo([suggest]), complemento([that, 'Stat3', plays, an, important, role, in, the, early, stage, of, 'megakaryopoiesis,', presumably, through, the, expansion, of, megakaryocytic, progenitor, cells])]). relacion([sujeto(['We', now]), verbo([report]), complemento([characterization, of, the, mutant, phenotype, and, the, identification, of, the, gene, mutated, in, 'vlt(m651)'])]). relacion([sujeto(['The', nonsense, mutation, was, located, 'C-terminal', to, the, two, zinc, fingers, and, resulted, in, a, truncated, protein, that, was, unable, to]), verbo([bind]), complemento(['DNA', or, mediate, 'GATA-specific', transactivation])]). relacion([sujeto(['Gene', therapy, of, many, genetic, diseases]), verbo([requires]), complemento([permanent, gene, transfer, into, 'self-renewing', stem, cells, and, restriction, of, transgene, expression, to, specific, progenies])]). relacion([sujeto(['We', developed, a, strategy, for, transcriptional]), verbo([targeting]), complemento([of, lentiviral, vectors, based, on, replacing, the, viral, long, terminal, repeat, '(', 'LTR)', enhancer, with, cell, 'lineage-specific,', genomic, control, elements])]). relacion([sujeto(['The', modified, 'LTR', was, used, to, drive, the, expression, of, a, reporter, gene, '(', the, green, fluorescent, protein, '[', 'GFP]', 'gene),', while, a, second, gene, '(', a, truncated, form, of, the, p75, nerve, growth, factor, receptor, '[', 'DeltaLNGFR])', was, placed, under, the, control, of, an, internal, constitutive, promoter, to, monitor, cell, 'transduction,', or, to, immunoselect, transduced, 'cells,', independently, from, the, expression, of, the]), verbo([targeted]), complemento([promoter])]). relacion([sujeto(['The', transcriptionally]), verbo([targeted]), complemento([vectors, were, used, to, transduce, cell, 'lines,', human, 'CD34+', hematopoietic, 'stem-progenitor', 'cells,', and, murine, bone, marrow, '(', 'BM)-repopulating', stem, cells])]). relacion([sujeto(['Cloning', of, the, woodchuck, hepatitis, virus, posttranscriptional, regulatory, element, at, a, defined, position, in, the]), verbo([targeted]), complemento([vector, allowed, selective, accumulation, of, the, genomic, transcripts, with, respect, to, the, internal, 'RNA', 'transcript,', with, no, loss, of, 'cell-type', restriction])]). relacion([sujeto(['A', critical, advantage, of, this]), verbo([targeting]), complemento([strategy, is, the, use, of, a, 'spliced,', major, viral, transcript, to, express, a, therapeutic, gene, and, that, of, an, 'internal,', independently, regulated, promoter, to, express, an, additional, gene, for, either, cell, marking, or, in, vivo, selection, purposes])]). relacion([sujeto(['The', expression, of, the, 'beta-like', globin, genes, is, intricately]), verbo([regulated]), complemento([by, a, series, of, both, general, and, 'tissue-restricted', transcription, factors])]). relacion([sujeto(['The', hemapoietic, 'lineage-specific', transcription, factor, 'GATA-1', is, important, for, erythroid, differentiation, and]), verbo([has]), complemento([been, implicated, in, regulating, the, expression, of, the, 'erythroid-specific', genes, including, the, genes, of, the, 'beta-globin', locus])]). relacion([sujeto(['In', the, human, erythroleukemic, 'K562', cell, 'line,', only, one, 'DNA', region]), verbo([has]), complemento([been, identified, previously, as, a, putative, site, of, 'GATA-1', interaction, by, in, vivo, footprinting, studies])]). relacion([sujeto(['We', mapped, 'GATA-1']), verbo([binding]), complemento([throughout, the, 'beta-globin', locus, by, using, 'chIp-chip', analysis, of, 'K562', cells])]). relacion([sujeto(['We']), verbo([found]), complemento([that, 'GATA-1', binds, in, a, region, encompassing, the, 'HS2', core, 'element,', as, was, previously, 'identified,', and, an, additional, region, of, 'GATA-1', binding, upstream, of, the, gammaG, gene])]). relacion([sujeto(['This', approach, will, be, of, general, utility, for, mapping, transcription, factor]), verbo([binding]), complemento([sites, within, the, 'beta-globin', locus, and, throughout, the, genome])]). relacion([sujeto(['The', distal, locus, control, region, '(', 'LCR)', is]), verbo([required]), complemento([for, 'high-level', expression, of, the, complex, of, genes, '(', 'HBBC)', encoding, the, 'beta-like', globins, of, mammals, in, erythroid, cells])]). relacion([sujeto(['Sequence', conservation, and, direct, experimental, evidence]), verbo([have]), complemento([implicated, sequences, within, and, between, the, 'HS', cores, in, function, of, the, 'LCR'])]). relacion([sujeto(['In', this]), verbo([report]), complemento([we, confirm, the, mapping, of, a, minor, 'HS', between, 'HS3', and, 'HS4,', called, 'HS3'])]). relacion([sujeto([2, ',', and, show, that, sequences, including, it]), verbo([increase]), complemento([the, number, of, random, integration, sites, at, which, a, drug, resistance, gene, is, expressed])]). relacion([sujeto(['We', also, show, that]), verbo([nuclear]), complemento([proteins, including, 'GATA1', and, 'Oct1', bind, specifically, to, sequences, within, 'HS3'])]). relacion([sujeto(['However,', the, protein, 'Pbx1,', whose]), verbo([binding]), complemento([site, is, the, best, match, to, one, highly, conserved, 'sequence,', does, not, bind, strongly])]). relacion([sujeto(['GATA1', and, 'Oct1', also]), verbo([bind]), complemento([in, the, 'HS', cores, of, the, 'LCR', and, to, promoters, in, 'HBBC'])]). relacion([sujeto(['Their']), verbo([binding]), complemento([to, this, minor, 'HS', suggests, that, they, may, be, used, in, assembly, of, a, large, complex, containing, multiple, regulatory, sequences])]). relacion([sujeto(['Unexpectedly,', 'FSH', negatively]), verbo([regulated]), complemento(['GATA-1', '(', but, not, 'GATA-4)', mRNA, in, a, 'dose-dependent', manner, in, primary, cultures, of, rat, 'Sertoli', cells, isolated, from, 21, -, 'd-old', animals])]). relacion([sujeto(['GATA-1', mRNA, was, also, negatively]), verbo([regulated]), complemento([by, cAMP, in, a, 'dose-', and, 'time-dependent', manner, in, 'MA-10,', a, mouse, 'Leydig', tumor, cell, line])]). relacion([sujeto(['Inhibin', 'alpha-subunit', 'mRNA,', on, the, other, 'hand,', was, evidently]), verbo([increased]), complemento([by, cAMP, treatment, in, both, 'MA-10', and, 'Sertoli', cells])]). relacion([sujeto(['The', 'GATA-1', mRNA]), verbo([expressed]), complemento([in, 'MEL,', a, mouse, erythroid, leukemia, cell, 'line,', was, not, affected, by, cAMP])]). relacion([sujeto(['The', reduction, of, 'GATA-1', mRNA, by, cAMP, can, be]), verbo([prevented]), complemento([when, a, translational, 'inhibitor,', 'cycloheximide,', is, added])]). relacion([sujeto(['In', 'summary,', we, demonstrated, that, gonadotropins, via, cAMP, negatively]), verbo([regulate]), complemento([the, mRNA, and, protein, levels, of, 'GATA-1,', but, not, 'GATA-4,', in, testicular, cells])]). relacion([sujeto(['Genes', that, are]), verbo([required]), complemento([specifically, for, the, definitive, 'program,', or, for, both, phases, of, 'hematopoiesis,', have, been, described])]). relacion([sujeto(['However,', a, specific, regulator, of, primitive, hematopoiesis]), verbo([has]), complemento([yet, to, be, reported])]). relacion([sujeto(['The', zebrafish, bloodless, '(', 'bls)', mutation]), verbo([causes]), complemento([absence, of, embryonic, erythrocytes, in, a, dominant, but, incompletely, penetrant, manner])]). relacion([sujeto(['Expression', analysis, of, hematopoietic, genes]), verbo([suggests]), complemento([that, formation, of, primitive, hematopoietic, precursors, is, deficient, in, bls, mutants, and, those, few, blood, precursors, that, are, specified, fail, to, differentiate, and, undergo, apoptosis])]). relacion([sujeto(['Overexpression', of, 'scl,', but, not, bmp4, or, 'gata1,', can]), verbo([lead]), complemento([to, partial, rescue, of, embryonic, blood, cells, in, bls])]). relacion([sujeto(['These', observations, demonstrate, that, the, bls, gene, product, is, uniquely]), verbo([required]), complemento([in, a, 'non-cell', autonomous, manner, for, primitive, 'hematopoiesis,', potentially, acting, via, regulation, of, scl])]). relacion([sujeto(['Multiple', myeloma, '(', 'MM)', is]), verbo([associated]), complemento([with, severe, 'normochromic/normocytic', anemia])]). relacion([sujeto(['This', study, demonstrates, that, the, abnormal, 'up-regulation', of, apoptogenic, 'receptors,', including, both, 'Fas', ligand, '(', 'L)', and, tumor, necrosis, 'factor-related', 'apoptosis-inducing', ligand, '(', 'TRAIL),', by, highly, malignant, myeloma, cells, is]), verbo([involved]), complemento([in, the, pathogenesis, of, the, ineffective, erythropoiesis, and, chronic, exhaustion, of, the, erythroid, matrix])]). relacion([sujeto(['The', evidence, that, 'Fas-L(+)/TRAIL(+)', malignant, plasma, cells, prime, erythroblast, apoptosis, by, direct, cytotoxicity, was, also, supported, by, the]), verbo([increase]), complemento([of, 'FLICE', in, fresh, immature, 'GpA(+dim)', erythroid, 'cells,', whereas, 'ICE', and, 'caspase-10', increased, in, subsequent, maturative, forms])]). relacion([sujeto(['Thus,', defining, the, mechanisms, by, which, the, 'GATA-1', gene, and, protein, are]), verbo([regulated]), complemento([should, provide, important, clues, regarding, the, establishment, of, erythroid, and, megakaryocytic, programs, of, gene, expression, in, committed, cells, and, their, maintenance, thereafter, in, maturing, precursors])]). relacion([sujeto(['Such', research, is, expected, to]), verbo([provide]), complemento([insights, into, the, mechanisms, involved, in, hematopoietic, commitment])]). relacion([sujeto(['GATA1', is, the, 'X-linked', transcriptional, activator]), verbo([required]), complemento([for, megakaryocyte, and, erythrocyte, differentiation])]). relacion([sujeto(['Missense', mutations, in, the, 'N-terminal', zinc, finger, '(', 'Nf)', of, 'GATA1', result, in, abnormal, 'hematopoiesis,', as, documented, in, four, 'families:', the, mutation, 'V205M']), verbo([leads]), complemento([to, both, severe, macrothrombocytopenia, and, dyserythropoietic, 'anemia,', 'D218G', to, macrothrombocytopenia, and, mild, dyserythropoiesis, without, 'anemia,', 'G208S', to, macrothrombocytopenia, and, 'R216Q', to, macrothrombocytopenia, with, 'beta-thalassemia'])]). relacion([sujeto(['The', three, first, 'GATA1', mutants, display, a, disturbed]), verbo([binding]), complemento([to, their, essential, transcription, cofactor, 'FOG1,', whereas, the, fourth, mutant, shows, an, abnormal, direct, 'DNA', binding])]). relacion([sujeto(['Zinc', finger, interaction, studies, revealed, a, stronger]), verbo([loss]), complemento([of, affinity, of, 'D218Y-GATA1', than, of, 'D218G-GATA1', for, 'FOG1', and, a, disturbed, 'GATA1', 'self-association'])]). relacion([sujeto(['The', 'D218Y', allele, '(', as, opposed, to, the, 'D218G', 'allele)', was, not]), verbo([expressed]), complemento([in, the, platelets, of, a, female, carrier, while, her, leukocytes, showed, a, skewed, 'X-inactivation', pattern])]). relacion([sujeto(['We', conclude, that, the, nature, of, the, amino, acid, substitution, at, position, 218, of, the, 'Nf', of, 'GATA1', is, of, crucial, importance, in, determining, the, severity, of, the, phenotype, in, 'X-linked', macrothrombocytopenia, patients, and, possibly, also, in]), verbo([inducing]), complemento([skewed, 'X', inactivation])]). relacion([sujeto(['Human', parvovirus, 'B19', '(', 'B19)', infection, during, pregnancy, is]), verbo([associated]), complemento([with, the, adverse, foetal, outcome, known, as, 'non-immune', hydrops, fetalis, '(', 'NIHF)'])]). relacion([sujeto(['Although', 'B19', is, known, to, infect, 'erythroid-lineage', cells, in, vivo, as, well, as, in, 'vitro,', the, mechanism]), verbo([leading]), complemento([to, the, occurrence, of, 'NIHF', is, not, clear])]). relacion([sujeto(['To', investigate, the, possible, involvement, of, the, 'B19', 'non-structural', protein, 'NS1', in, 'NIHF,', three, independent, lines, of, transgenic, mice, were, generated, that]), verbo([expressed]), complemento(['NS1', under, the, control, of, the, 'Cre-loxP', system, and, the, 'GATA1', promoter])]). relacion([sujeto(['Two', of, the, three, lines]), verbo([expressed]), complemento(['NS1', in, 'erythroid-lineage', cells])]). relacion([sujeto(['Most', of, the, transgenic, mice, died, at, the, embryonic, 'stage,', some, of, which, developed, hydropic, changes]), verbo([caused]), complemento([by, severe, anaemia, at, embryonic, day, 15.5, '(', 'E15'])]). relacion([sujeto(['The', 'NS1-transgenic', mouse, lines, established, here]), verbo([provide]), complemento([an, animal, model, for, human, 'NIHF', and, suggest, that, 'NS1', plays, a, crucial, role, in, the, adverse, outcome, associated, with, intrauterine, 'B19', infection, in, humans])]). relacion([sujeto(['Their', early, 'expression,', already, in, evidence, within, multipotential, hematopoietic, cell, 'lines,']), verbo([has]), complemento([made, it, difficult, to, determine, what, extracellular, effectors, and, transduction, mechanisms, might, be, directing, the, onset, of, their, own, transcription, during, embryogenesis])]). relacion([sujeto(['To', circumvent, this, 'problem,', we]), verbo([have]), complemento([taken, the, novel, approach, of, investigating, whether, the, ability, of, embryonic, stem, '(', 'ES)', cells, to, mimic, early, developmental, patterns, of, cellular, expression, during, embryoid, body, '(', 'EB)', differentiation, can, address, this, issue])]). relacion([sujeto(['Surprisingly,', in, addition, to, 'mesoderm,', these, cells]), verbo([expressed]), complemento([hemangioblast, and, hematopoietic, markers])]). relacion([sujeto(['However,', they, did, not]), verbo([express]), complemento([the, committed, erythroid, markers, 'EKLF', and, 'GATA1,', nor, the, terminally, differentiated, 'beta-like', globin, markers])]). relacion([sujeto(['Using', this, 'system,', we, determined, that, 'EB', differentiation, in, 'BMP4', was, necessary, and, sufficient, to, recover, 'EKLF', and, 'GATA1', expression, and, could, be, further]), verbo([stimulated]), complemento([by, the, inclusion, of, 'VEGF,', 'SCF,', erythropoietin, and, thyroid, hormone])]). relacion([sujeto(['EBs', were, competent, to]), verbo([respond]), complemento([to, 'BMP4', only, until, day, 4, of, 'differentiation,', which, coincides, with, the, normal, onset, of, 'EKLF', expression])]). relacion([sujeto(['The', direct, involvement, of, the, 'BMP/Smad', pathway, in, this, induction, process, was, further, verified, by, showing, that, erythroid, expression, of, a, dominant, negative, 'BMP1B', receptor, or, of, the, inhibitory, 'Smad6', protein]), verbo([prevented]), complemento([induction, of, 'EKLF', or, 'GATA1', even, in, the, presence, of, serum])]). relacion([sujeto(['Although', 'Smad1,', 'Smad5', and, 'Smad8', are, all]), verbo([expressed]), complemento([in, the, 'EBs,', 'BMP4', induction, of, 'EKLF', and, 'GATA1', transcription, is, not, immediate])]). relacion([sujeto(['These', data, implicate, the, 'BMP/Smad', induction, system, as, being, a, crucial, pathway, to, direct, the, onset, of, 'EKLF', and, 'GATA1', expression, during, hematopoietic, differentiation, and, demonstrate, that, 'EB', differentiation, can, be, manipulated, to, study, induction, of, specific, genes, that, are]), verbo([expressed]), complemento([early, within, a, lineage])]). relacion([sujeto(['Red', cell, development, depends, on, the]), verbo([binding]), complemento([of, erythropoietin, '(', 'EPO)', to, receptors, expressed, by, erythroid, 'colony-forming', units, '(', 'CFUe)', and, the, subsequent, activation, of, 'receptor-bound', 'Janus', kinase, '(', 'Jak2)'])]). relacion([sujeto(['Jak2', then]), verbo([mediates]), complemento([the, phosphorylation, of, receptor, tyrosine, sites, and, the, recruitment, of, 25, or, more, 'Src', homology, 2, 'domain-encoding', proteins, and, associated, factors])]). relacion([sujeto(['Previous', studies]), verbo([have]), complemento([shown, that, an, 'EPO', receptor, form, containing, 'Jak2-binding', domains, plus, a, single, 'phosphotyrosine(343)', '(', 'PY(343))-STAT5-binding', site, provides, all, signals, needed, for, erythroid, cell, development])]). relacion([sujeto(['To', study, activities, of, a, 'PY-null', 'EPO', receptor, in, primary, cells, while, avoiding, compensatory, 'mechanisms,', a, form]), verbo([retaining]), complemento([domains, for, 'Jak2', binding, and, 'activation,', but, lacking, all, cytoplasmic, tyrosine, 'sites,', was, expressed, in, transgenic, mice, from, a, 'GATA1', 'gene-derived', vector, as, a, human, epidermal, growth, factor, 'receptor-', murine, 'EPO', receptor, chimera, '(', 'EE-T-Y343F)'])]). relacion([sujeto(['Interestingly,', this, 'PY-null', 'EPO', receptor, form, supported, 'CFUe', development, '(', in, the, absence, of, detectable, 'STAT5', 'activation)', at, efficiencies, within, 3, -, fold, of, those, levels]), verbo([mediated]), complemento([by, either, an, 'EE-T-Y343', form, or, the, endogenous, 'EPO', receptor])]). relacion([sujeto(['In', tests, of, cosignaling, with, 'c-Kit,', 'EE-T-Y343F', nonetheless]), verbo([retained]), complemento([full, capacity, to, synergize, with, 'c-Kit', in, promoting, erythroid, progenitor, cell, proliferation])]). relacion([sujeto(['HEL', 'cells,', a, human, erythroleukemia, cell, 'line,', mainly]), verbo([express]), complemento([the, fetal, '(', 'gamma)', globin, gene, and, trace, amount, of, the, embryonic, '(', 'epsilon)', globin, 'gene,', but, not, adult, '(', 'beta)', globin, gene])]). relacion([sujeto(['Here', we, show, that, hydroxyurea, '(', 'HU)', can]), verbo([induce]), complemento(['HEL', cells, to, express, adult, '(', 'beta)', globin, gene, and, lead, these, cells, to, terminal, differentiation])]). relacion([sujeto(['Results', showed, in, 'Gel', mobility, shift, assays, that, 'GATA', factors, could, specifically]), verbo([bind]), complemento([to, the, regulatory, elements, of, human, 'beta-globin', 'gene,', including, the, proximal, regulatory, element, '(', the, 'beta-promoter)', and, the, distal, regulatory, elements, '(', the, 'DNase', 'I', hypersensitive, sites, in, the, 'LCR,', 'HS2-HS4', core, 'sequences)'])]). relacion([sujeto(['However,', the, 'DNA']), verbo([binding]), complemento([patterns, of, 'GATA', factors, were, quite, different, between, 'HU-induced', and, uninduced, 'HEL', cells])]). relacion([sujeto(['Western-blot', analysis, of]), verbo([nuclear]), complemento([extracts, from, both, the, uninduced, and, 'HU-induced', 'HEL', cells, revealed, that, the, level, of, 'GATA-2', transcription, factor, 'decreased,', whereas, the, level, of, 'GATA-1', transcription, factor, increased, following, the, time, of, hydroxyurea, induction])]). relacion([sujeto(['Furthermore,', using, 'RT-PCR', analysis, the, expression, of, human, 'beta-globin', gene, in, 'HU-induced', 'HEL', cells, could, be, blocked, again, when, 'HEL', cells, were, incubated, in, the, presence, of, antisense, oligonucleotides, for, 'hGATA-1,']), verbo([suggesting]), complemento([that, the, upregulation, of, 'hGATA-1', transcription, factor, might, be, critical, for, the, expression, of, human, 'beta-globin', gene, in, 'HU-induced', 'HEL', cells])]). relacion([sujeto(['The', objective, of, this, work, was, to, 'identify,', in, the, context, of, chromosomally, integrated, 'DNA,', the, contribution, of, defined, transcription, factor]), verbo([binding]), complemento([motifs, to, the, function, of, a, complex, retrovirus, enhancer, in, hematopoietic, cells, in, vivo])]). relacion([sujeto(['Repopulating', murine, hematopoietic, cells, were, transduced, with, equal, gene, dosages, of, 'replication-incompetent', retrovirus, vectors, encoding]), verbo([enhanced]), complemento([green, fluorescent, protein])]). relacion([sujeto(['Destruction', of, 'GC-rich', sites, representing, overlapping]), verbo([targets]), complemento([for, 'SP1', or, 'EGR1', uniformly, attenuated, gene, expression, '(', approximately, 25, to, 70, '%', of, 'wild-type', 'levels)', in, all, hematopoietic, 'lineages,', as, shown, by, multicolor, flow, cytometry, of, peripheral, blood, and, bone, marrow, cells, at, various, time, points, posttransplantation])]). relacion([sujeto(['In', 'contrast,', a, point, mutation, within, a, dual, 'ETS/GATA', motif, that, abolished, transactivation, by, 'ETS', factors, but, not, by, 'GATA-1', slightly]), verbo([increased]), complemento([activity, in, erythroid, cells, and, significantly, attenuated, enhancer, function, in, 'T', lymphocytes])]). relacion([sujeto(['This', study, shows, that, controlled, gene, transfer, in, transplantable, hematopoietic, cells, allows, a, functional, analysis, of, distinct, cis, elements, within, a, complex, retrovirus, 'enhancer,', as]), verbo([required]), complemento([for, the, characterization, and, engineering, of, various, cellular, and, viral, regulatory, sequences, in, basic, research, and, gene, therapy])]). relacion([sujeto(['Although', erythropoietin, '(', 'EPO)', and, its, receptor, '(', 'EPOR)', are, crucial, for, the, 'proliferation,', 'survival,', and, terminal, differentiation, of, erythroid, 'progenitors,', it, remains, to, be, elucidated, whether, 'EPOR-unique', signaling, is]), verbo([required]), complemento([for, erythropoiesis])]). relacion([sujeto(['In', methylcellulose, clonal, culture, of, fetal, liver, '(', 'FL)', cells, of, generated, 'hGMR-expressing', 'EPOR(-/-)', embryos, at, embryonic, day, '(', 'E)', 12.5, of, 'gestation,', 'hGM-CSF']), verbo([stimulated]), complemento([erythroid, colony, formation, under, 'serum-containing', and, 'serum-free', conditions])]). relacion([sujeto([5, 'FL', 'cells;']), verbo([enhanced]), complemento(['adult,', but, not, 'embryonic,', globin, 'synthesis;', and, induced, increase, of, 'GATA-1', expression, and, decrease, of, erythroid, 'Kruppel-like', factor, and, cMyb, expression, in, the, 'FL', cells])]). relacion([sujeto([0, yolk, sac, 'erythropoiesis,', both, substances, had, a, similar, effect, on, erythroid, colony, 'formation,', but, 'hGM-CSF']), verbo([induced]), complemento([an, increase, of, 'beta-major', globin, 'expression,', while, 'EPO', did, not])]). relacion([sujeto(['All', 'together,', the, results, of, the, present, study, demonstrated, that, 'hGM-CSF', can]), verbo([stimulate]), complemento([the, proliferation, and, differentiation, of, primitive, and, definitive, erythroid, cells, independently, of, 'EPOR', signal, if, they, express, 'hGMR,', and, the, activity, is, comparable, to, that, of, 'EPO', in, 'definitive,', but, not, 'primitive,', erythropoiesis])]). relacion([sujeto(['The', developmental, processes]), verbo([leading]), complemento([from, the, mesoderm, to, primitive, and, definitive, haematopoietic, and, endothelial, 'lineages,', although, of, great, 'importance,', are, still, poorly, defined])]). relacion([sujeto(['Recent', studies]), verbo([have]), complemento([suggested, a, model, in, which, common, precursors, give, rise, to, endothelial, progenitors, and, haematopoietic, 'progenitors,', the, latter, subsequently, generating, both, primitive, and, definitive, haematopoietic, lineages])]). relacion([sujeto(['However,', this, model, is, contradicted, by, findings, that]), verbo([suggest]), complemento([the, emergence, of, haematopoietic, cells, from, the, endothelial, lineage])]). relacion([sujeto(['We']), verbo([found]), complemento([sequential, steps, in, the, differentiation, of, 'FLK1+', mesoderm, into, haematopoietic, and, endothelial, lineages, in, an, in, vitro, differentiation, system, of, embryonic, stem, '(', 'ES)', 'cells:', '(', 'i)', the, 'GATA-1+', subset, of, 'FLK1+', mesodermal, cells, loses, the, capacity, to, give, rise, to, endothelial, cells, and, is, restricted, to, primitive, 'erythroid,', macrophage, and, definitive, erythroid, 'progenitors;', '(', 'ii)', the, remaining, 'GATA-1-', cells, give, rise, to, 'VE-cadherin+', endothelial, 'cells;', and, subsequently, '(', 'iii)', multiple, definitive, haematopoietic, progenitors, and, endothelial, cells, branch, off, from, a, subset, of, 'VE-cadherin+', cells])]). relacion([sujeto(['These', observations, strongly]), verbo([suggest]), complemento([that, the, divergence, of, primitive, and, multilineage, definitive, 'haematopoietic/endothelial', lineages, occurs, 'first,', and, then, multilineage, definitive, haematopoietic, progenitors, arise, from, 'VE-cadherin+', endothelial, cells, in, the, development, of, haematopoietic, and, endothelial, cells])]). relacion([sujeto(['Microsatellite', linkage, analysis, identified, a, region, of, the, 'X', chromosome, including, the, 'GATA-1', 'gene,', which, encodes, a, critical, transcription, factor]), verbo([involved]), complemento([in, erythrocyte, and, megakaryocyte, development])]). relacion([sujeto(['By', sequencing, the, entire, coding, region, of, 'GATA-1,', a, 2, -, base, mutation, was, detected, that, results, in, a, single, amino, acid, substitution, '(', glycine, 208, to, 'serine)', within, a, highly]), verbo([conserved]), complemento([portion, of, the, 'N-terminal', zinc, finger, domain])]). relacion([sujeto(['Although', not]), verbo([required]), complemento([for, 'DNA', 'binding,', 'Gly208', of, 'GATA-1', is, involved, in, direct, interaction, with, 'Friend', of, 'GATA-1', '(', 'FOG),', a, cofactor, required, for, normal, megakaryocytic, and, erythroid, development])]). relacion([sujeto(['These', results, demonstrate, that, the, 'GATA-1-FOG', interaction, is, partially, disrupted, by, the, mutation, and, that, the, greatest, effect]), verbo([involves]), complemento([contact, with, the, 'FOG', zinc, finger, 9])]). relacion([sujeto(['These', findings, help, describe, a, novel, mutation, of, 'GATA-1', in, humans, as, a]), verbo([cause]), complemento([of, 'X-linked', 'thrombocytopenia,', and, they, confirm, the, vital, role, played, by, this, transcription, factor, during, in, vivo, megakaryocyte, development])]). relacion([sujeto(['Two', isoforms, that, differ, in, the, presence, of, exons, 6, and, 7, ',', 'Vegf(165)', and, 'Vegf(121),', are, the, dominant, forms]), verbo([expressed]), complemento([in, zebrafish, embryo])]). relacion([sujeto(['Simultaneous', overexpression, of, both, isoforms, in, the, embryo, results, in]), verbo([increased]), complemento([production, of, 'flk1,', 'tie1,', 'scl,', and, gata1, 'transcripts,', indicating, a, stimulation, of, both, endothelial, and, hematopoietic, lineages])]). relacion([sujeto(['We', also, demonstrate, that, vegf, can]), verbo([stimulate]), complemento([hematopoiesis, in, zebrafish, by, promoting, the, formation, of, terminally, differentiated, red, blood, cells])]). relacion([sujeto(['Simultaneous', overexpression, of, both, isoforms, also]), verbo([causes]), complemento([ectopic, vasculature, and, blood, cells, in, many, of, the, injected, embryos, as, well, as, pericardial, edema, in, later, stage, embryos])]). relacion([sujeto(['Overexpression', of, vegf, also, resulted, in, earlier, onset, of, 'flk1,', 'tie1,', 'scl,', and, gata1, expression, in, the, 'embryo,', indicating, a, possible, role, of, vegf, in]), verbo([stimulating]), complemento([the, differentiation, of, both, vascular, and, hematopoietic, lineages])]). relacion([sujeto(['Co-injection', of, 'RNAs', for, both, isoforms, results, in]), verbo([increased]), complemento([expression, of, three, of, these, markers, over, and, above, that, observed, when, either, 'RNA', is, singly, injected, and, analysis, of, vegf, expression, in, the, notochord, mutants, no, tail, and, floating, head, suggests, that, the, notochord, patterns, the, formation, of, the, dorsal, aorta, by, stimulating, adjacent, somite, cells, to, express, 'vegf,', which, in, turn, functions, as, a, signal, in, dorsal, aorta, patterning])]). relacion([sujeto(['These', results, show, that, in, the, zebrafish, 'embryo,', vegf, can, not, only]), verbo([stimulate]), complemento([endothelial, cell, differentiation, but, also, hematopoiesis])]). relacion([sujeto(['Patients', with, paroxysmal, nocturnal, hemoglobinuria, '(', 'PNH)']), verbo([have]), complemento([blood, cells, deficient, in, glycosyl, phosphatidylinositol, '(', 'GPI)-linked', proteins, owing, to, a, somatic, mutation, in, the, 'X-linked', 'PIGA', gene])]). relacion([sujeto(['To']), verbo([target]), complemento(['Piga', recombination, to, the, 'erythroid/megakaryocytic', lineage, in, 'mice,', the, 'Cre/loxP', system, was, 'used,', and, 'Cre', was, expressed, under, the, transcriptional, regulatory, sequences, of, 'GATA-1'])]). relacion([sujeto(['Breeding', of, 'GATA1-cre', '(', 'G)', transgenic, mice, with, mice, carrying, a, floxed, 'Piga', '(', 'L)', allele, was]), verbo([associated]), complemento([with, high, embryonic, lethality])]). relacion([sujeto(['The']), verbo([loss]), complemento([of, 'GPI-linked', proteins, on, the, cell, surface, occurred, late, in, erythroid, 'differentiation,', causing, a, proportion, of, red, cells, to, express, low, residual, levels, of, 'GPI-linked', proteins])]). relacion([sujeto(['In', 'summary,', 'GATA1-Cre']), verbo([causes]), complemento(['high-efficiency', 'Piga', gene, inactivation, in, a, 'GATA-1-specific', pattern])]). relacion([sujeto(['For', the, first, 'time,', mice, were, generated, that]), verbo([have]), complemento([almost, 100, '%', of, red, cells, deficient, in, 'GPI-linked', proteins])]). relacion([sujeto(['To', investigate, the, contribution, of, individual, domains, of, 'GATA-1', to, its, 'activity,', transgenic, mice]), verbo([expressing]), complemento([either, an, 'N-terminus,', or, an, 'N-', or, 'C-terminal', zinc, finger, deletion, of, 'GATA-1', '(', 'Delta', 'NT,', 'Delta', 'NF', or, 'Delta', 'CF,', 'respectively)', were, generated, and, crossed, to, 'GATA-1', germline, mutant, '(', 'GATA-1'])]). relacion([sujeto(['However,', transgenic, mice]), verbo([expressing]), complemento(['Delta', 'NT,', but, not, the, 'Delta', 'NF', 'protein,', were, able, to, rescue, definitive, hematopoiesis])]). relacion([sujeto(['Thus,', 'lineage-specific', transgenic, rescue, of, the, 'GATA-1', mutant, mouse, revealed, novel, properties, that, are]), verbo([conferred]), complemento([by, specific, domains, of, 'GATA-1', during, primitive, and, definitive, 'erythropoiesis,', and, demonstrate, that, the, 'NT', and, 'NF', moieties, lend, 'complementary,', but, distinguishable, properties, to, the, function, of, 'GATA-1'])]). relacion([sujeto(['Genetic', studies]), verbo([have]), complemento([recently, provided, rich, insights, into, the, molecular, and, transcriptional, regulation, of, megakaryocyte, differentiation, and, thrombopoiesis])]). relacion([sujeto(['The', putative, transcriptional]), verbo([targets]), complemento([of, these, 'regulators,', including, the, 'NF-E2-dependent', 'hematopoietic-specific', 'beta-tubulin', isoform, 'beta1,', deepen, our, understanding, of, molecular, mechanisms, in, platelet, biogenesis])]). relacion([sujeto(['The', study, of, rare, syndromes, of, inherited, thrombocytopenia, in, mice, and, man]), verbo([has]), complemento([also, refined, the, emerging, picture, of, megakaryocyte, maturation])]). relacion([sujeto(['Synthesis', of, 'platelet-specific', organelles, is]), verbo([mediated]), complemento([by, a, variety, of, regulators, of, intracellular, vesicle, membrane, 'fusion,', and, platelet, release, is, coordinated, through, extensive, and, dynamic, reorganization, of, the, actin, and, microtubule, cytoskeletons])]). relacion([sujeto(['As', in, other, aspects, of, 'hematopoiesis,', characterization, of, recurrent, chromosomal, translocations, in, human, leukemias]), verbo([provides]), complemento([an, added, dimension, to, the, molecular, underpinnings, of, megakaryocyte, differentiation])]). relacion([sujeto(['The', 'Krüppel-like', transcription, factor, 'Biklf', is, preferentially]), verbo([expressed]), complemento([in, blood, islands, throughout, zebrafish, 'embryogenesis,', marking, the, region, of, future, erythropoiesis, '[', 1, ']'])]). relacion([sujeto(['In', this, 'paper,', we, show, that, expression, of, biklf, is, significantly]), verbo([suppressed]), complemento([in, the, 'blood-less', mutants, vampire, and, m683, in, which, primitive, hematopoiesis, is, impaired])]). relacion([sujeto(['Knockdown', of, biklf, using, 'morpholino-based', antisense, oligonucleotides, '(', 'biklf-MO)']), verbo([led]), complemento([to, a, potent, reduction, in, the, number, of, circulating, blood, cells, and, deficiency, in, hemoglobin, production])]). relacion([sujeto(['Consistently,', we]), verbo([found]), complemento([that, the, expression, of, 'beta(e3)globin', is, strongly, suppressed, in, 'biklf-MO-injected', 'embryos,', while, gata1, expression, is, partly, inhibited, at, the, 10, -, somite, stage])]). relacion([sujeto(['In', 'addition,', analysis, of, reporter, constructs, driven, by, the, 'GATA1', and, 'beta-globin', promoters, showed, that, 'Biklf', can, positively]), verbo([regulate]), complemento([both, genes])]). relacion([sujeto(['These', results, indicate, that, 'Biklf', is]), verbo([required]), complemento([for, erythroid, cell, differentiation, in, zebrafish])]). relacion([sujeto(['We']), verbo([have]), complemento([shown, previously, that, the, tyrosine, kinase, 'Lyn', is, involved, in, differentiation, signals, emanating, from, an, activated, erythropoietin, receptor])]). relacion([sujeto(['Here', we, demonstrate, that, 'Lyn']), verbo([interacts]), complemento([with, thyroid, hormone, 'receptor-interacting', protein, 1, '(', 'Trip-1),', a, transcriptional, regulator, associated, with, the, 'T(3)', 'receptor,', providing, a, link, between, the, 'Epo', and, 'T(3)', signaling, pathways])]). relacion([sujeto(['Trip-1', 'co-localized', with, 'Lyn', and, the, 'T(3)', receptor, alpha, in, the, 'cytoplasm/plasma', membrane, of, erythroid, cells, but, translocated, to, discrete]), verbo([nuclear]), complemento([foci, shortly, after, 'Epo-induced', differentiation])]). relacion([sujeto(['Our', data]), verbo([reveal]), complemento([that, 'T(3)', stimulated, the, proliferation, of, immature, erythroid, 'cells,', and, inhibited, maturation, promoted, by, erythropoietin])]). relacion([sujeto(['Removal', of, 'T(3)', reduced, cell, division, and]), verbo([enhanced]), complemento([terminal, differentiation])]). relacion([sujeto(['This', was, accompanied, by, large]), verbo([increases]), complemento([in, the, cell, cycle, inhibitor, 'p27(Kip1)', and, by, increasing, expression, of, erythroid, transcription, factors, 'GATA-1,', 'EKLF,', and, 'NF-E2'])]). relacion([sujeto(['Strikingly,', a, truncated, 'Trip-1']), verbo([inhibited]), complemento([both, 'erythropoietin-induced', maturation, and, 'T(3)-initiated', cell, division])]). relacion([sujeto(['This', mutant, 'Trip-1']), verbo([acted]), complemento([in, a, dominant, negative, fashion, by, eliminating, endogenous, 'Lyn,', elevating, 'p27(Kip1),', and, blocking, 'T(3)', response, elements])]). relacion([sujeto(['These', data, demonstrate, that, 'Trip-1', can, simultaneously]), verbo([modulate]), complemento([responses, involving, both, cytokine, and, nuclear, receptors])]). relacion([sujeto(['During', erythrocytic, differentiation, of, murine, erythroleukemia, '(', 'MEL)', cells]), verbo([induced]), complemento([by, 'dimethylsulfoxide,', expression, of, 'TfR1', 'increased,', whereas, 'TfR2', decreased])]). relacion([sujeto(['In', 'MEL', 'cells,', expression, of, 'TfR1', was]), verbo([induced]), complemento([by, 'desferrioxamine,', an, iron, 'chelator,', and, it, was, reduced, by, ferric, nitrate])]). relacion([sujeto(['Reporter', assay, showed, that, 'GATA-1,', an, 'erythroid-specific', transcription, factor, essential, for, erythrocytic, differentiation, at, relatively, early, 'stages,']), verbo([enhanced]), complemento(['TfR2', promoter, activity])]). relacion([sujeto(['Interestingly,', 'FOG-1,', a, cofactor, of, 'GATA-1']), verbo([required]), complemento([for, erythrocyte, 'maturation,', repressed, the, enhancement, of, the, activity, by, 'GATA-1'])]). relacion([sujeto(['Also,', 'CCAAT-enhancer']), verbo([binding]), complemento(['protein,', which, is, abundant, in, 'liver,', enhanced, the, promoter, activity])]). relacion([sujeto(['Expression', profiles, of, 'TfR2', were, different, from, those, of, 'TfR1,']), verbo([suggesting]), complemento([unique, functions, for, 'TfR2,', which, may, be, involved, in, iron, 'metabolism,', hepatocyte, 'function,', and, erythrocytic, differentiation])]). relacion([sujeto(['Expression', of, gata1, is]), verbo([regulated]), complemento([through, multiple, 'cis-acting', 'GATA', motifs])]). relacion([sujeto(['To', elucidate, regulatory, mechanisms, of, the, gata1, 'gene,', we]), verbo([have]), complemento([used, zebrafish])]). relacion([sujeto(['To', examine, whether, 'GATA1']), verbo([regulates]), complemento([its, own, gene, 'expression,', we, microinjected, into, embryos, a, 'GFP', reporter, gene, linked, successively, to, the, gata1, gene, regulatory, region, and, to, 'GATA1', mRNA])]). relacion([sujeto(['Surprisingly,', ectopic, expression, of, the, reporter, gene, was]), verbo([induced]), complemento([at, the, site, of, 'GATA1', overexpression, and, was, dependent, on, the, distal, double, 'GATA', motif])]). relacion([sujeto(['Functional', domain, analyses, using, transgenic, fish, lines, that, harbor, the, 'gata1-GFP', reporter, construct, revealed, that, both, the, 'N-', and, 'C-terminal', 'zinc-finger', domains, of, 'GATA1,', hence, intact, 'GATA1', 'function,', are]), verbo([required]), complemento([for, the, ectopic, 'GFP', expression])]). relacion([sujeto(['These', results]), verbo([provide]), complemento([the, first, in, vivo, evidence, that, gata1, gene, expression, undergoes, positive, autoregulation])]). relacion([sujeto(['The', 'follicle-stimulating', hormone, receptor, '(', 'FSHR)', gene, is]), verbo([expressed]), complemento([in, 'Sertoli', cells, in, males, and, in, granulosa, cells, in, females])]). relacion([sujeto(['Cis-acting', sequences, and]), verbo([associated]), complemento([binding, factors, responsible, for, the, transcription, of, the, 'TATA-less', 'FSHR', gene, in, 'Sertoli', cells, were, analyzed, with, dimethylsulfate, '(', 'DMS)', footprinting, assays, and, electrophoretic, mobility, shift, assay, '(', 'EMSA)'])]). relacion([sujeto(['In', vivo, footprints, in, the, core, promoter, using]), verbo([nuclear]), complemento([proteins, from, 'Sertoli', cells, identified, several, protected, 'sequences,', including, an, inverted, 'GATA', '(', 'TATC,', -, 88, /, -, 85, ')', ',', and, an, 'E2F', '(', 'TTTCGCG,', -, 45, /, -, 39, ')', motif])]). relacion([sujeto(['EMSA', showed, the, presence, of, one, or, more, 'sequence-specific', proteins]), verbo([interacting]), complemento([with, these, potential, regulatory, elements])]). relacion([sujeto(['Antibody-supershift', assays, as, well, as, competition, assays, further, revealed, that, 'testis-specific', 'GATA-1']), verbo([recognized]), complemento([the, inverted, 'GATA', element])]). relacion([sujeto(['The', mutational, analysis, indicated, that, the, 'GATA', and, 'E2F', elements, were, each]), verbo([required]), complemento([for, optimal, promoter, activity])]). relacion([sujeto(['The', mammalian, transcription, factor, 'GATA-1', is]), verbo([required]), complemento([for, normal, erythroid, and, megakaryocytic, development])]). relacion([sujeto(['GATA-1', contains, two, zinc, 'fingers,', the, 'C-terminal', 'finger,', which, is, known, to]), verbo([bind]), complemento(['(', 'A/T)GATA(A/G)', motifs, in, 'DNA', and, the, 'N-finger,', which, is, important, for, interacting, with, 'co-regulatory', proteins, such, as, 'Friend', of, 'GATA', '(', 'FOG)'])]). relacion([sujeto(['We', now, show, 'that,', like, the, 'C-finger,', the, 'N-finger', of, 'GATA-1', is, also, capable, of]), verbo([binding]), complemento(['DNA', but, recognizes, distinct, sequences, with, the, core, 'GATC'])]). relacion([sujeto(['We', demonstrate, that, the, 'GATA-1', 'N-finger', can]), verbo([bind]), complemento([these, sequences, in, vitro, and, that, in, cellular, 'assays,', 'GATA-1', can, activate, promoters, containing, 'GATC', motifs])]). relacion([sujeto(['Experiments', with, mutant, 'GATA-1', proteins, confirm, the, importance, of, the, 'N-finger,', as, the, 'C-finger', is, not]), verbo([required]), complemento([for, transactivation, from, 'GATC', sites])]). relacion([sujeto(['Recently', four, naturally, occurring, mutations, in, 'GATA-1']), verbo([have]), complemento([been, shown, to, be, associated, with, familial, blood, disorders])]). relacion([sujeto(['We']), verbo([have]), complemento([investigated, the, effect, of, these, mutations, on, the, recognition, of, 'GATC', sites, by, the, 'N-finger', and, show, that, one, mutation, 'R216Q', abolishes, 'DNA', 'binding,', whereas, the, others, have, only, minor, effects])]). relacion([sujeto(['The', molecular, basis, for, the, observed, phenotype, is, a, substitution, of, glycine, for, aspartate, in, the, strictly]), verbo([conserved]), complemento([codon, 218, '(', 'D218G)', of, the, 'amino-terminal', zinc, finger, loop, of, the, transcription, factor, 'GATA1'])]). relacion([sujeto(['Zinc', finger, interaction, studies, demonstrated, that, this, mutation, results, in, a, weak]), verbo([loss]), complemento([of, affinity, of, 'GATA1', for, its, essential, cofactor, 'FOG1,', whereas, direct, 'D218G-GATA1', binding, to, 'DNA', was, normal])]). relacion([sujeto(['The', phenotypic, effects, of, this, mutation, in, the, 'patients\'', platelets]), verbo([have]), complemento([been, studied])]). relacion([sujeto(['Semiquantitative', 'RNA', 'analysis,', normalized, for, 'beta-actin', messenger, 'RNA,', showed, extremely, low, transcription, of, the, 'GATA1']), verbo([target]), complemento([genes, 'GPIbbeta', and, 'GPIX', but, also, a, significantly, lower, expression, of, the, nondirectly, 'GATA1-regulated', 'Gsalpha', 'gene,', suggestive, of, incomplete, megakaryocyte, maturation])]). relacion([sujeto(['In', 'conclusion,', 'GATA1', mutations, can]), verbo([lead]), complemento([to, isolated, 'X-linked', macrothrombocytopenia, without, anemia])]). relacion([sujeto(['Among', various, 'cytokines,', 'interleukin-3', '(', 'IL-3)']), verbo([induced]), complemento([erythroid, precursor, cells, that, expressed, the, 'erythroid-specific', 'GATA-1', and, 'beta-major', globin])]). relacion([sujeto(['SCF', and, 'IL-3']), verbo([induced]), complemento([stepwise, generation, of, erythroid, precursor, cells, from, an, 'A-6', hematopoietic, stem, cell, line])]). relacion([sujeto([1, ')', but]), verbo([have]), complemento([a, normal, hematocrit, '(', 'Hct)', '(', approximately])]). relacion([sujeto(['Both', the, 'GATA-1(low)', and, the, normal, mice]), verbo([respond]), complemento([to, 'PHZ', and, 'EPO', with, similar, '(', 2, -, to, 3, -, 'fold)', increases, in, size, and, cellularity, of, the, spleen, '(', increases, are, limited, mostly, to, 'cells,', both, progenitor, and, 'precursor,', of, the, erythroid, 'lineage)'])]). relacion([sujeto(['However,', in, spite, of, the, similar, relative, cellular, 'increases,', the]), verbo([increases]), complemento([of, all, these, cell, populations, are, significantly, 'higher,', in, absolute, cell, 'numbers,', in, the, mutant, than, in, the, 'wild-type', mice])]). relacion([sujeto(['In', 'conclusion,', the, 'GATA-1(low)', mutation]), verbo([increases]), complemento([the, magnitude, of, the, response, to, erythroid, stimuli, as, a, consequence, of, the, expansion, of, the, erythroid, progenitor, cells, in, their, spleen])]). relacion([sujeto(['Cathepsin', 'E', is, an, intracellular, aspartic, proteinase, that, is, considered, to]), verbo([have]), complemento([a, number, of, physiological, roles, including, antigen, processing])]). relacion([sujeto(['Quantitation', of, procathepsin, 'E', mRNA, by, 'LightCyclertrade', mark, technology, indicated, that, the, gene, was]), verbo([transcribed]), complemento([in, lung, but, not, in, kidney, of, both, human, and, mouse, origin])]). relacion([sujeto(['Regulation', of, human, and, mouse, procathepsin, 'E', gene, expression, was, shown, not, to, be, influenced, by, the, extent, of, 'CpG', methylation, but, depended, on, the, recognition, of, potential]), verbo([binding]), complemento([motifs, in, each, promoter, region, by, transcription, factors, such, as, 'GATA1,', 'PU1', and, 'YY1,', as, revealed, by, functional, analysis, using, a, series, of, 'promoter/luciferase', reporter, gene, fusion, constructs])]). relacion([sujeto(['Thus', the, extent, to, which, the, procathepsin, 'E', gene, is]), verbo([expressed]), complemento([in, a, particular, cell, type, may, depend, on, the, balance, between, the, effects, produced, by, 'positive-acting,', 'cell-specific', transcription, factors, such, as, 'GATA1', and, 'PU1', and, the, negative, influence, of, the, ubiquitous, 'YY1', factor])]). relacion([sujeto(['We']), verbo([found]), complemento([that, the, population, of, megakaryocyte, progenitors, in, the, fetal, 'liver,', yolk, 'sac,', and, peripheral, blood, of, jumonji, homozygotes, increased])]). relacion([sujeto(['This', abnormality, is]), verbo([caused]), complemento([by, delayed, growth, arrest, in, the, progeny])]). relacion([sujeto(['The', megakaryocytes, of, jumonji, homozygotes]), verbo([expressed]), complemento(['PF4,', 'CD62P,', and, 'GATA-1,', obtained, cytoplasmic, 'maturation,', extended, 'proplatelet-like', 'processes,', and, underwent, endomitosis])]). relacion([sujeto(['The']), verbo([loss]), complemento([of, the, jumonji, gene, causes, an, increase, in, the, number, of, megakaryocyte, lineage, cells])]). relacion([sujeto(['Our', data]), verbo([suggest]), complemento([that, the, jumonji, gene, regulates, proliferation, but, not, differentiation, of, megakaryocyte, lineage, cells])]). relacion([sujeto(['Although', normal, megakaryocytic, development]), verbo([has]), complemento([been, shown, to, require, the, presence, of, functional, 'GATA-1', and, 'NF-E2', transcription, factors, in, 'vivo,', the, roles, of, other, members, of, the, 'GATA', binding, factors, and, 'NF-E2', family, during, megakaryocytic, differentiation, are, unclear])]). relacion([sujeto([the, present, 'study,', the, expression, of, 'GATA', family, 'members,', 'GATA-1', and, 'GATA-2,', a, 'GATA-binding', 'factor,', 'EVI-1,', the, large, subunit, of, 'NF-E2', 'factor,', p45, and, the, related, 'factors,', 'Nrf1,', 'Nrf2,', 'Nrf3,', 'BACH1,', 'BACH2,', and, the, small, subunit, of, 'NF-E2,', 'MAFK', and, 'MAFG']), verbo([has]), complemento([been, examined, in, human, megakaryocytic, and, erythroid, cells, by, reverse, 'transcriptase-polymerase', chain, reaction])]). relacion([sujeto(['CD34+', cells, isolated, from, human, cord, blood, were]), verbo([induced]), complemento([to, unilineage, megakaryocytic, or, erythroid, differentiation, in, liquid, suspension, culture, in, the, presense, of, thrombopoietin, or, 'erythropoietin,', respectively])]). relacion([sujeto(['In', megakaryocytic, 'culture,', 'p45,', 'Nrf1,', 'Nrf2,', 'BACH1,', 'MAFK', and, 'MAFG', mRNAs, were]), verbo([induced]), complemento([similarly, to, erythroid, culture])]). relacion([sujeto(['BACH2', was]), verbo([induced]), complemento([only, in, megakaryocytic, 'culture,', although, the, level, of, expression, was, low])]). relacion([sujeto(['Furthermore,', the, profiles, of, transcription, factors]), verbo([involved]), complemento([in, 'hematopoiesis,', 'EVI-1', and, 'Ets-1', mRNAs, were, induced, only, in, megakaryocytic, culture])]). relacion([sujeto(['The', dynamic, changes, in, the, levels, of, different, transcription, factors, that, occur, during, primary, megakaryocytic, differentiation]), verbo([suggest]), complemento([that, the, levels, of, these, factors, may, influence, the, progression, to, specific, hematopoietic, pathways])]). relacion([sujeto(['Sequencing', the, recently, discovered, 'erythroid-specific', promoter, in, six, patients, with, a, single, undefined, allele, identified, four, novel, mutations, clustered, in, a, 20, -, bp, 'region:', '(', 'a)', a, -, 70, 'T', to, 'C', transition, in, a, putative, 'GATA-1', consensus]), verbo([binding]), complemento(['element,', '(', 'b)', a, -, 76, 'G', to, 'A', 'transition,', '(', 'c)', a, -, 86, 'C', to, 'A', transversion, in, three, unrelated, 'patients,', and, '(', 'd)', a, -, 90, 'C', to, 'A', transversion, in, a, putative, 'CP2', binding, motif])]). relacion([sujeto(['When', transfected, into, 'K562', erythroid, 'cells,', these, constructs, yielded, 3, +, /, -, 1, ',', 54, +, /, -, 3, ',', 43, +, /, -, 6, ',', and, 8, +, /, -, 1, '%', ',', 'respectively,', of, the, reporter, activity]), verbo([conferred]), complemento([by, the, 'wild-type', promoter])]). relacion([sujeto(['Thus,', these, four, pathogenic, erythroid, promoter, mutations, impaired, 'erythroid-specific', 'transcription,']), verbo([caused]), complemento(['CEP,', and, identified, functionally, important, 'GATA1', and, 'CP2', transcriptional, binding, elements, for, 'erythroid-specific', heme, biosynthesis])]). relacion([sujeto(['GATA', transcription, factors]), verbo([bind]), complemento([the, consensus, sequence, 'WGATAR,', present, in, the, flanking, regions, of, most, erythroid, specific, genes])]). relacion([sujeto(['Conserved', 'GATA', sites, were]), verbo([found]), complemento([in, each, of, the, hypersensitive, sites, in, both, 'beta-and', alpha, clusters, and, in, proximal, regulatory, regions, of, the, 'zeta-,', 'epsilon-', and, 'gamma-globin', but, not, the, 'alpha,', delta, or, 'beta-globin', genes])]). relacion([sujeto(['We', then, tested, the, effect, of]), verbo([increasing]), complemento([levels, of, 'GATA-1', and, 'GATA-2', on, the, expression, of, endogenous, globin, genes, in, human, erythroid, cells])]). relacion([sujeto(['Increasing', 'GATA-1', levels, in, 'K562', cells]), verbo([decreased]), complemento([the, levels, of, 'epsilon-globin', mRNA, but, had, no, effect, on, the, levels, of, expression, of, 'gamma,', zeta, or, 'alpha-globin', genes])]). relacion([sujeto(['Increasing', 'GATA-2', levels]), verbo([increased]), complemento(['epsilon-globin', and, 'gamma-globin', transcripts])]). relacion([sujeto(['Increasing', levels, of, 'GATA-1', also]), verbo([caused]), complemento([a, decrease, in, the, expression, of, endogenous, 'GATA-2,', while, increased, levels, of, 'GATA-2', had, no, effect, on, 'GATA-1', mRNA])]). relacion([sujeto(['Our', results, indicate, a, differential, role, of, 'GATA-1', and, -, 2, transcription, factors, on, globin, transcripts, and]), verbo([suggest]), complemento([a, correlation, between, the, conservation, of, 'GATA', sites, in, the, regulatory, regions, and, the, ability, of, endogenous, globin, genes, to, respond, to, 'GATA', transcription, factors])]). relacion([sujeto(['They', also]), verbo([suggest]), complemento([that, quantitative, changes, in, the, levels, of, 'GATA-1', or, 'GATA-2', can, result, in, alterations, of, globin, target, gene, expression, and, may, participate, in, the, ontogenic, control, of, the, globin, genes])]). relacion([sujeto(['The', 'GATA-1', transcription, factor, is, capable, of]), verbo([suppressing]), complemento([the, myeloid, gene, expression, program, when, ectopically, expressed, in, myeloid, cells])]). relacion([sujeto(['We']), verbo([found]), complemento([that, 'GATA-1', is, capable, of, suppressing, the, myeloid, phenotype, without, interfering, with, 'PU'])]). relacion([sujeto([1, gene, 'expression,', but, instead, was, capable, of]), verbo([inhibiting]), complemento([the, activity, of, the, 'PU'])]). relacion([sujeto(['This', inhibition, was, independent, of, the, ability, of, 'GATA-1', to]), verbo([bind]), complemento(['DNA,', suggesting, that, it, is, mediated, by, 'protein-protein', interaction])]). relacion([sujeto([1, to]), verbo([interact]), complemento([with, 'GATA-1', and, found, a, direct, interaction, between, the, 'PU'])]). relacion([sujeto([1, 'ETS', domain, with, the, 'GAL4', 'DNA-binding', domain, removed, the, ability, of, 'GATA-1', to]), verbo([inhibit]), complemento(['PU'])]). relacion([sujeto([1, 'DNA-binding', 'domain,', rather, than, the, transactivation, 'domain,', is, the]), verbo([target]), complemento([for, 'GATA-1-mediated', repression])]). relacion([sujeto(['We', therefore, propose, that, 'GATA-1', represses, myeloid, gene, 'expression,', at, least, in, 'part,', through, its, ability, to, directly]), verbo([interact]), complemento([with, the, 'PU'])]). relacion([sujeto([2000, ;, 95, :, 2543, -, 2551, ')', 'Using', a, combination, of, mouse, bacterial, artificial, chromosome, '(', 'BAC)', genomic, library, 'screening,', 'long-range', polymerase, chain, reaction, '(', 'PCR)', 'amplification,', genomic, walking, and, 'DNA', 'sequencing,', we]), verbo([have]), complemento([characterized, the, 'intron/exon', 'boundaries,', the, sizes, of, each, intron, and, 5, '\'', flanking, region, of, the, mouse, 'PFK-C', gene])]). relacion([sujeto(['However,', 'PFK-C']), verbo([has]), complemento([much, larger, intronic, sequences, throughout, the, gene])]). relacion([sujeto(['Sequence', analysis, of, the, 'PFK-C', 5, '\'', flanking, region, revealed, that, it, is, devoid, of, 'TATA', and, 'CAAT', boxes, at, the, usual, 'positions,', but, it, contained, several, putative]), verbo([binding]), complemento([sites, for, transcription, factors, 'AP1,', 'GATA1,', 'NKX2'])]). relacion([sujeto(['The', 5, '\'', flanking, region, was, not, enriched, in, 'GC', dinucleotides, and, lacked, 'CpG', islands, and, putative]), verbo([binding]), complemento([sites, for, 'SP1'])]). relacion([sujeto(['Four', transcription, initiation, sites]), verbo([have]), complemento([been, identified, by, 'full-length', 'RNA', 'ligase-mediated', rapid, amplification, of, cDNA, ends, '(', 'RLM-RACE)', between, -, 61, and, -, 32, bp, from, the, translation, initiation, codon])]). relacion([sujeto(['PFK-A', mRNA, was, more, abundantly]), verbo([expressed]), complemento([in, all, tissues, than, were, the, 'PFK-B', and, 'PFK-C', genes])]). relacion([sujeto(['Based', on, the, mouse, 'PFK-C', signal, normalized, to, 18, 'S', 'rRNA,', the, 'PFK-C', mRNA, was]), verbo([expressed]), complemento([at, the, highest, levels, in, the, 'brain,', 'heart,', thymus, and, 'testicles,', whereas, low, levels, were, observed, in, the, 'kidney,', 'liver,', 'muscle,', and, lung])]). relacion([sujeto(['The', transcriptional, coactivator, 'CREB']), verbo([binding]), complemento([protein, '(', 'CBP)', possesses, intrinsic, histone, acetyltransferase, '(', 'HAT)', activity, that, is, important, for, gene, regulation])]). relacion([sujeto(['CBP']), verbo([binds]), complemento([to, and, cooperates, with, numerous, nuclear, factors, to, stimulate, 'transcription,', but, it, is, unclear, if, these, factors, modulate, 'CBP', 'HAT', activity])]). relacion([sujeto(['Our', previous, work, showed, that, 'CBP']), verbo([interacts]), complemento([with, the, 'Epstein-Barr', 'virus-encoded', basic, region, zipper, '(', 'b-zip)', 'protein,', 'Zta,', and, augments, its, transcriptional, activity])]). relacion([sujeto(['Here', we]), verbo([report]), complemento([that, 'Zta', strongly, enhances, 'CBP-mediated', acetylation, of, nucleosomal, histones])]). relacion([sujeto(['Zta']), verbo([stimulated]), complemento([the, 'HAT', activity, of, 'CBP', that, had, been, partially, purified, or, immunoprecipitated, from, mammalian, cells, as, well, as, from, 'affinity-purified,', baculovirus, expressed, 'CBP'])]). relacion([sujeto(['Stimulation', of, nucleosome, acetylation]), verbo([required]), complemento([the, 'CBP', 'HAT', 'domain,', the, 'Zta', 'DNA', binding, and, transcription, activation, 'domain,', and, nucleosomal, 'DNA'])]). relacion([sujeto(['In', addition, to, 'Zta,', we]), verbo([found]), complemento([that, two, other, 'b-zip', 'proteins,', 'NF-E2', and, 'C/EBPalpha,', strongly, stimulated, nucleosomal, 'HAT', activity])]). relacion([sujeto(['In', 'contrast,', several, 'CBP-binding', 'proteins,', including, 'phospho-CREB,', 'JUN/FOS,', 'GATA-1,', 'Pit-1,', and, 'EKLF,', failed, to]), verbo([stimulate]), complemento(['HAT', activity])]). relacion([sujeto(['These', results, demonstrate, that, a, subset, of, transcriptional, activators]), verbo([enhance]), complemento([the, 'nucleosome-directed', 'HAT', activity, of, 'CBP', and, suggest, that, nuclear, factors, may, regulate, transcription, by, altering, substrate, recognition, 'and/or', the, enzymatic, activity, of, chromatin, modifying, coactivators])]). relacion([sujeto(['We']), verbo([have]), complemento([previously, reported, that, 'CDV', '(', carnitine, 'deficiency-associated', gene, expressed, in, 'ventricle)-1', was, a, downregulated, gene, in, the, hypertrophied, ventricle, of, 'carnitine-deficient', juvenile, visceral, steatosis, mice, and, that, the, related, gene, '(', 'CDV-1R)', showed, no, tissue, specificity, and, no, sensitivity, to, carnitine, deficiency])]). relacion([sujeto(['We']), verbo([found]), complemento([that, the, 'CDV-1/1R', gene, consisted, of, at, least, 19, exons, and, encompassed, approximately, 48, kb])]). relacion([sujeto(['The', presumed, promoter, sequence, for, 'CDV-1', located, in, the, intron, 14, of, 'CDV-1R', contained, the, common, 'TATA', box, and, consensus]), verbo([binding]), complemento([sites, for, various, transcription, factors, '(', 'Nkx-2'])]). relacion([sujeto(['In', the, upstream, region, of, the, 'CDV-1', 'promoter,', we]), verbo([found]), complemento([two, 'VNTRs,', 13, repeats, of, 'GATA1,', and, 16, copies, of, 'STRE', involved, in, yeast, stress, response])]). relacion([sujeto(['All', these, data, revealed, that, two, mRNA, 'species,', 'CDV-1', and, 'CDV-1R,', are]), verbo([expressed]), complemento(['tissue-specifically', by, using, promoters, peculiar, to, each, transcript, in, a, single, gene])]). relacion([sujeto(['Human', 'FcgammaRIIA,']), verbo([expressed]), complemento([on, 'platelets,', 'neutrophils,', and, 'macrophages,', plays, a, major, role, in, platelet, activation, and, immune, clearance])]). relacion([sujeto(['EMSA', analyses, demonstrate, specific]), verbo([binding]), complemento([of, both, 'GATA-1', and, 'GATA-2', to, labeled, oligonucleotides, containing, the, putative, 'GATA', site, with, 'HEL', but, not, 'U937', '(', 'myelomonocytic)', nuclear, extracts])]). relacion([sujeto(['Antibodies', to, 'NF-Y', supershift, the, specific, -, 119, 'NF-Y', complex, with, 'HEL,', 'U937,', 'Jurkat', '(', 'T-lymphocytic),', and, 'HeLa', '(', 'nonhematopoietic)']), verbo([nuclear]), complemento([extracts])]). relacion([sujeto(['Comparison', of, the, activity, of, 'GATA', and, 'NF-Y', mutant, constructs, in, 'HEL', and, 'U937', demonstrates, that, while, either, 'GATA', or, 'NF-Y', mutation, results, in, a, large]), verbo([decrease]), complemento([in, the, promoter, activity, '(', 2.2, -, and, 2.3, -, 'fold,', 'respectively)', in, 'HEL', 'cells,', neither, mutation, is, effective, in, reducing, activity, in, 'U937', cells])]). relacion([sujeto(['This', is, the, first, example, of, a, promoter, active, in, the, megakaryocyte, lineage, in, which, 'NF-Y', cooperates, additively, with, 'GATA', factors, to]), verbo([regulate]), complemento([transcription])]). relacion([sujeto(['Luciferase', reporter, assays, demonstrated, that, the, housekeeping, promoter, was, active, in, both, erythroid, 'K562', and, 'HeLa', 'cells,', while, the, erythroid, promoter, was, active, only, in, erythroid, cells, and, its, activity, was]), verbo([increased]), complemento([during, 'hemin-induced', erythroid, differentiation])]). relacion([sujeto(['Thus,', human, 'URO-synthase', expression, is]), verbo([regulated]), complemento([during, erythropoiesis, by, an, 'erythroid-specific', alternative, promoter])]). relacion([sujeto(['Mammalian', 'CBFB', encodes, a, transcription, factor, '(', 'CBF', 'beta)', that, in, combination, with, 'CBF', alpha, 2]), verbo([binds]), complemento([to, specific, 'DNA', sequences, and, regulates, expression, of, a, number, of, hematopoietic, genes])]). relacion([sujeto(['CBFB', is]), verbo([associated]), complemento([with, human, leukemias, through, a, chromosome, 16, inversion, and, is, essential, for, definitive, hematopoiesis, during, mouse, embryo, development])]). relacion([sujeto(['We']), verbo([have]), complemento([isolated, a, zebrafish, cbfb, complementary, 'DNA', '(', 'cDNA)', clone, from, a, zebrafish, kidney, cDNA, library])]). relacion([sujeto(['In', biochemical, 'analyses,', cbfbeta]), verbo([binds]), complemento([to, human, 'CBF', alpha, 2, and, enhances, its, 'DNA', binding])]). relacion([sujeto(['During', zebrafish, 'development,', cbfb, is]), verbo([expressed]), complemento([in, the, lateral, plate, mesoderm, at, tail, bud, stage, and, in, the, intermediate, cell, mass, '(', 'ICM,', the, location, of, embryonic, 'hematopoiesis)', between, the, 21, -, to, 26, -, somite, stages])]). relacion([sujeto(['The', cbfb, is, also]), verbo([expressed]), complemento([in, 'Rohon-Beard', 'cells,', cranial, nerve, 'ganglia,', 'hindbrain,', 'retina,', branchial, 'arches,', 'jaw,', and, fin, buds])]). relacion([sujeto(['Expression', of, cbfb, is]), verbo([decreased]), complemento([or, absent, in, the, 'ICM', and, 'Rohon-Beard', cells, in, some, hematopoietic, mutants, and, is, unaffected, in, others])]). relacion([sujeto(['We']), verbo([have]), complemento([also, analyzed, the, expression, of, scl, and, 'gata-1', in, the, same, hematopoietic, mutants, to, ascertain, the, relative, order, of, these, transcription, factors, to, cbfb, in, zebrafish, hematopoiesis])]). relacion([sujeto(['Our', results, indicate, that, cbfb, is]), verbo([expressed]), complemento([in, early, hematopoietic, progenitors, and, that, its, expression, pattern, in, the, hematopoietic, mutants, is, similar, to, that, of, scl])]). relacion([sujeto(['To', define, how, 'GATA-1']), verbo([regulates]), complemento([megakaryocyte, cell, growth, we, searched, for, mRNA, transcripts, expressed, in, primary, 'wild-type,', but, not, 'GATA-1(-),', megakaryocytes])]). relacion([sujeto(['One', differentially]), verbo([expressed]), complemento([transcript, encodes, inositol, polyphosphate, 4, -, phosphatase, type, 'I', '(', 4, -, 'Ptase', 'I)'])]). relacion([sujeto(['This', enzyme, hydrolyses, phosphatidylinositol, 3, ',', 4, -, bisphosphate, and, also]), verbo([has]), complemento([lesser, activity, against, soluble, analogues, of, this, 'lipid,', inositol, 3, ',', 4, -, bisphosphate, and, inositol, 1, ',', 3, ',', 4, -, triphosphate])]). relacion([sujeto(['Reintroduction', of, 4, -, 'Ptase', 'I', into, both, primary, 'GATA-1(-)', and, 'wild-type', megakaryocytes, significantly, retards, cell, 'growth,']), verbo([suggesting]), complemento([that, absence, of, 4, -, 'Ptase', 'I', may, contribute, to, the, hyperproliferative, phenotype, of, 'GATA-1(-)', megakaryocytes])]). relacion([sujeto(['Zinc', finger, domains]), verbo([have]), complemento([traditionally, been, regarded, as, 'sequence-specific', 'DNA', binding, motifs])]). relacion([sujeto(['However,', recent, evidence, indicates, that, many, zinc, fingers]), verbo([mediate]), complemento([specific, 'protein-protein', interactions])]). relacion([sujeto(['For', 'instance,', several, zinc, fingers, from, 'FOG', family, proteins]), verbo([have]), complemento([been, shown, to, interact, with, the, 'N-terminal', zinc, finger, of, 'GATA-1'])]). relacion([sujeto(['We']), verbo([have]), complemento([used, 'NMR', spectroscopy, to, determine, the, first, structures, of, two, 'FOG', family, zinc, fingers, that, are, involved, in, 'protein-protein', 'interactions:', fingers, 1, and, 9, from, 'U-shaped'])]). relacion([sujeto(['[', 15, 'N,(1)H]-HSQC', titrations]), verbo([have]), complemento([been, used, to, define, the, 'GATA', binding, surface, of, 'USH-F1,', and, comparison, with, other, 'FOG', family, proteins, indicates, that, the, recognition, mechanism, is, conserved, across, species])]). relacion([sujeto(['The', surface, of, 'FOG-type', fingers, that]), verbo([interacts]), complemento([with, 'GATA-1', overlaps, substantially, with, the, surface, through, which, classical, fingers, typically, recognize, 'DNA'])]). relacion([sujeto(['This']), verbo([suggests]), complemento([that, these, fingers, could, not, contact, both, 'GATA', and, 'DNA', simultaneously])]). relacion([sujeto(['In', 'addition,', results, from, 'NMR,', gel, 'filtration,', and, sedimentation, equilibrium, experiments]), verbo([suggest]), complemento([that, the, interactions, are, of, moderate, affinity])]). relacion([sujeto(['Our', results, demonstrate, unequivocally, that, zinc, fingers, comprising, the, classical, betabetaalpha, fold, are, capable, of]), verbo([mediating]), complemento([specific, contacts, between, proteins])]). relacion([sujeto(['The', existence, of, this, alternative, function]), verbo([has]), complemento([implications, for, the, prediction, of, protein, function, from, sequence, data, and, for, the, evolution, of, protein, function])]). relacion([sujeto(['The', transcriptional, coactivator, 'CREB-binding', protein, '(', 'CBP)']), verbo([binds]), complemento([via, its, 'KIX', domain, to, the, activation, domain, of, 'c-Myb', and, mediates, 'c-Myb-dependent', transcriptional, activation])]). relacion([sujeto(['Here', we, demonstrate, that, the, 'C/H2', domain, of, 'CBP,', which, is, critical, for, the, acetyltransferase, 'activity,', also, directly]), verbo([interacts]), complemento([with, the, negative, regulatory, domain, '(', 'NRD)', of, 'c-Myb'])]). relacion([sujeto(['In', 'addition,', 'CBP', acetylated, 'c-Myb', in, vivo, not, only, at, the, sites]), verbo([found]), complemento([in, this, study, but, also, at, the, 'p300-induced', acetylation, sites, reported, recently])]). relacion([sujeto(['Replacement', of, lysine, by, arginine, at, all, of, these, sites, dramatically]), verbo([decreased]), complemento([the, 'trans-activating', capacity, of, 'c-Myb'])]). relacion([sujeto(['The', results, of, transcriptional, activation, assays, with, 'c-Myb', acetylation, site, mutants]), verbo([suggested]), complemento([that, acetylation, of, 'c-Myb', at, each, of, these, five, sites, synergistically, enhances, 'c-Myb', activity])]). relacion([sujeto(['Thus,', acetylation, of, 'c-Myb', by, 'CBP']), verbo([increases]), complemento([the, 'trans-activating', capacity, of, 'c-Myb', by, enhancing, its, association, with, 'CBP'])]). relacion([sujeto(['The', 'CCAAT', boxes, of, the, 'beta-like', globin, genes]), verbo([interact]), complemento([with, three, 'proteins:', 'NF-Y,', 'GATA-1', and, 'NFE-6'])]). relacion([sujeto(['Elevated', levels, of, 'C/EBPgamma,', but, not, 'C/EBPgammaDeltaB,']), verbo([increase]), complemento([expression, of, the, '(', 'fetal)', 'gamma-globin', relative, to, the, '(', 'adult)', 'beta-globin', gene])]). relacion([sujeto(['Interestingly,', fetal, liver, erythropoiesis, is, ablated, when, the, 'C/EBPgamma', and, 'C/EBPgammaDeltaB', levels, are, further]), verbo([increased]), complemento([in, homozygous, transgenics])]). relacion([sujeto(['We']), verbo([suggest]), complemento([that, targeted, expression, of, 'dominant-negative', leucine, zipper, proteins, is, a, generally, applicable, approach, to, ablate, specific, tissues, in, mice])]). relacion([sujeto(['Mutations', in, the, 'PKLR', gene, responsible, for, pyruvate, kinase, '(', 'PK)-deficient', anaemia, are, mainly, located, in, the, coding, 'regions:', 11, are, in, the, splicing, sites, 'and,', 'recently,', three, mutations]), verbo([have]), complemento([been, described, in, the, promoter, region])]). relacion([sujeto(['We', now]), verbo([report]), complemento([a, novel, point, mutation, 'A-->G', on, nucleotide, 72, ',', upstream, from, the, initiation, codon, of, the, 'PKLR', 'gene,', in, four, 'Portuguese', 'PK-deficient', patients])]). relacion([sujeto(['The', mRNA, level, was, about, five, times, lower, than, in, normal, 'controls,', demonstrating, that, the, 'PKLR', gene, transcription, is, severely, 'affected,', most, probably, because, the, -, 72, 'A-->G', point, mutation, disables, the]), verbo([binding]), complemento([of, the, erythroid, transcription, factor, 'GATA-1', to, the, 'GATA-A', element])]). relacion([sujeto(['Optimal', production, of, red, cells, in, vivo]), verbo([requires]), complemento([collaboration, between, 'c-Kit,', erythropoietin, receptor, '(', 'Epo-R),', and, 'GATA-1'])]). relacion([sujeto(['Utilizing', an, embryonic, stem, 'cell-derived', erythroid, progenitor, cell, line, from, mice, deficient, in, 'GATA-1,', we]), verbo([have]), complemento([examined, the, role, of, 'c-Kit', and, 'Epo-R', in, erythroid, cell, 'proliferation,', 'survival,', and, differentiation])]). relacion([sujeto(['In', 'addition,', we, demonstrate, that, 'Epo-R', and, 'Stat5', are]), verbo([regulated]), complemento([by, a, 'second,', novel, mechanism])]). relacion([sujeto(['We', demonstrate, that, 'c-Kit', stimulation, by, stem, cell, factor, is, essential, for, the, maintenance, of, 'Epo-R', and, 'Stat5', protein, 'expression,', which, results, in, significantly]), verbo([enhanced]), complemento(['Bcl-x(L)', induction, and, survival, of, erythroid, progenitors, in, response, to, 'Epo', stimulation])]). relacion([sujeto(['Restoration', of, 'GATA-1', function, results, in, terminal, erythroid, maturation, and, 'up-regulation', of, 'Epo-R', and, 'Bcl-x(L)', 'expression,']), verbo([leading]), complemento([also, to, significantly, enhanced, survival, of, terminally, differentiating, erythroid, progenitors, in, the, presence, of, only, 'Epo'])]). relacion([sujeto(['These', results, demonstrate, that, 'c-Kit', and, 'Epo-R']), verbo([have]), complemento([unique, 'role(s)', during, distinct, phases, of, erythroid, 'maturation,', and, both, stem, cell, factor, and, 'Epo', contribute, to, the, regulation, of, the, 'Epo-R-Stat5-Bcl-x(L)', pathway, to, ensure, optimal, 'survival,', 'proliferation,', and, differentiation, of, erythroid, progenitors])]). relacion([sujeto(['The', 'HEL', 'cells,', a, human, erythroleukemia, cell, 'line,']), verbo([express]), complemento([mainly, the, fetal, globin, gene, and, small, amount, of, the, embryonic, '(', 'epsilon)', globin, 'gene,', but, not, the, adult, '(', 'beta)', globin, gene])]). relacion([sujeto(['Hydroxyurea,', a, small, organic, 'compound,']), verbo([has]), complemento([been, successfully, used, to, treat, sickle, cell, anemia, and, 'beta-thalessaemia'])]). relacion([sujeto(['Our', data, demonstrated, that, the, growth, rate, of, 'HEL', cell, proliferation, was]), verbo([inhibited]), complemento([by, different, doses, of, hydroxyurea, '(', from, 50, 'mumol/L', to, 200, 'mumol/L)'])]). relacion([sujeto(['Using', both, routine, 'RT-PCR', and, quantitative, 'PCR', 'analyses,', we, revealed, that, the, expression, of, 'beta-globin', gene, was, sharply]), verbo([activated]), complemento([and, 'alpha-globin', gene, was, almost, completely, silenced, when, 'HEL', cells, were, induced, for, 3, or, 5, days])]). relacion([sujeto(['Meanwhile,', 'gamma-globin', gene, was]), verbo([expressed]), complemento([with, no, much, difference, between, induced, and, uninduced, 'HEL', cells])]). relacion([sujeto(['We', also, demonstrated, that, the, expression, of, 'GATA-1', and, 'NF-E', 2, ',', which, were, two, of, the, most, important, transcription, factors, in, erythrocyte, 'development,', was]), verbo([activated]), complemento([about, 3, folds, in, the, induced, cells])]). relacion([sujeto(['We']), verbo([suggested]), complemento([that, the, induction, of, 'GATA-1', and, 'NF-E', 2, expression, by, hydroxyurea, might, lead, to, activation, of, the, adult, 'beta-globin', gene, through, some, pathways, of, signal, 'transduction,', 'therefore,', hydroxyurea, might, play, a, role, to, induce, 'HEL', cells, to, terminal, differentiation])]). relacion([sujeto([1, can, physically]), verbo([interact]), complemento([to, inhibit, each, 'other\'s', 'function,', but, the, mechanism, of, repression, of, 'GATA-1', function, by, 'PU'])]). relacion([sujeto([1]), verbo([has]), complemento([not, been, elucidated])]). relacion([sujeto([1, can, physically]), verbo([interact]), complemento([with, the, 'C-terminal', zinc, finger, of, 'GATA-1'])]). relacion([sujeto([1, 'N', 'terminus,', but, not, the, 'C', 'terminus,', is]), verbo([required]), complemento([for, inhibiting, 'GATA-1', function])]). relacion([sujeto([1, does, not, affect, the, expression, of, 'GATA-1', messenger, 'RNA,', 'protein,', or]), verbo([nuclear]), complemento([localization])]). relacion([sujeto(['However,', 'GATA-1', 'DNA']), verbo([binding]), complemento([decreases, dramatically])]). relacion([sujeto([1, had, a, similar, effect, in, the, 'G1ER', cell, 'line,', in, which, the, 'GATA-1', null, erythroid, cell, line, 'G1E']), verbo([has]), complemento([been, transduced, with, a, 'GATA-1-estrogen', receptor, fusion, 'gene,', which, is, directly, dependent, on, induction, of, the, 'GATA-1', fusion, protein, to, effect, erythroid, maturation])]). relacion([sujeto(['Consistent', with, in, vitro]), verbo([binding]), complemento(['assays,', overexpression, of, 'PU'])]). relacion([sujeto([1, blocked, 'DNA']), verbo([binding]), complemento([of, the, 'GATA-1', fusion, protein, as, well, as, 'GATA-1-mediated', erythroid, differentiation, of, these, 'G1ER', cells])]). relacion([sujeto(['These', results, demonstrate, a, novel, mechanism, by, which, function, of, a, 'lineage-specific', transcription, factor, is]), verbo([inhibited]), complemento([by, another, 'lineage-restricted', factor, through, direct, 'protein-protein', interactions])]). relacion([sujeto(['These', findings, contribute, to, understanding, how, 'protein-protein', interactions]), verbo([participate]), complemento([in, hematopoietic, differentiation, and, leukemogenesis])]). relacion([sujeto([2000, ;, 96, :, 2641, -, 2648, ')', 'Multiple', studies]), verbo([have]), complemento([shown, that, intracellular, signal, transduction, by, the, protein, kinase, 'C', '(', 'PKC)', family, participates, in, the, initiation, of, megakaryocyte, differentiation])]). relacion([sujeto(['Pharmacologic', profiles, of, induction, and, inhibition, of, megakaryocytic, differentiation, in, both, cell, lines]), verbo([suggested]), complemento([a, role, for, the, 'calcium-independent', novel, 'PKCs,', in, particular, 'PKC-epsilon'])]). relacion([sujeto(['The', functional, cooperation, between, 'GATA-1', and, 'PKC-epsilon', displayed, dependence, on, cellular, 'milieu,', as, well, as, on, the, promoter, context, of, 'GATA']), verbo([binding]), complemento([sites])]). relacion([sujeto(['In', 'aggregate,', the, data]), verbo([suggest]), complemento([that, 'PKC-epsilon', specifically, participates, in, megakaryocytic, lineage, commitment, through, functional, cooperation, with, 'GATA-1', in, the, activation, of, megakaryocytic, promoters])]). relacion([sujeto(['Targeted', gene, disruption, of, two, distinct, 'lineage-restricted', hematopoietic, transcription, factors]), verbo([has]), complemento([provided, useful, insights, into, the, transcriptional, control, of, platelet, production])]). relacion([sujeto(['Absence', of, either, the, basic, 'leucine-zipper', protein, 'NF-E2', or, of, the, 'zinc-finger', protein, 'GATA-1', in, vivo, results, in, severe, thrombocytopenia, secondary, to, distinct, patterns, of]), verbo([arrested]), complemento([megakaryocyte, cytoplasmic, 'maturation;', in, 'addition,', 'megakaryocyte-selective', loss, of, 'GATA-1', expression, leads, to, dysregulated, proliferation, of, progenitor, cells])]). relacion([sujeto(['The', ultrastructure, of, the, defective, megakaryocytes]), verbo([suggests]), complemento([that, absence, of, the, respective, transcription, factors, impairs, biogenesis, of, 'platelet-specific', granules, and, proper, development, and, organization, of, demarcation, membranes])]). relacion([sujeto(['In', 'particular,', transcriptional]), verbo([targets]), complemento([of, 'NF-E2', may, be, implicated, in, the, very, final, stages, of, megakaryocyte, 'differentiation,', which, involve, the, organization, and, release, of, platelets])]). relacion([sujeto(['Preliminary', characterization, of, genes, that, are, downregulated, in, 'NF-E2-/-', megakaryocytes, is, in, progress, and, is, likely, to]), verbo([lead]), complemento([to, mechanistic, insights, into, thrombocytopoiesis])]). relacion([sujeto(['The', transcription, factor, 'GATA-1', is, specifically]), verbo([expressed]), complemento([in, hematopoietic, lineages])]). relacion([sujeto(['Prior', gene, knockout, experiments, established, an, essential, role, for, 'GATA-1', in, red, blood, cell, 'production,', but, could, not]), verbo([provide]), complemento([direct, evidence, with, respect, to, a, requirement, in, megakaryopoiesis])]). relacion([sujeto(['We', summarize, here, recent, 'lineage-selective', gene]), verbo([targeting]), complemento([in, mice, that, establishes, critical, functions, for, 'GATA-1', in, controlling, megakaryocyte, growth, and, 'maturation,', and, platelet, production])]). relacion([sujeto(['Several', genes, that, affect, the, differentiation, 'of,', or, are]), verbo([expressed]), complemento([early, 'in,', both, the, endothelial, and, blood, lineages, may, in, fact, function, at, the, level, of, the, hemangioblast])]). relacion([sujeto(['The', transcription, factor, gene, scl, is]), verbo([expressed]), complemento([in, both, endothelial, and, blood, lineages, from, an, early, stage, and, can, regulate, their, differentiation])]). relacion([sujeto(['Here', we]), verbo([report]), complemento([that, in, zebrafish, the, homeobox, gene, hhex, '(', previously, called, 'hex)', is, also, expressed, in, endothelial, and, blood, lineages, from, an, early, stage])]). relacion([sujeto(['We']), verbo([find]), complemento([that, hhex, expression, in, these, lineages, is, significantly, reduced, in, cloche, mutant, 'embryos,', indicating, that, hhex, functions, downstream, of, cloche, to, regulate, endothelial, and, blood, differentiation])]). relacion([sujeto(['Ectopic', expression, of, hhex, through, injection, of, a, 'DNA', construct]), verbo([leads]), complemento([to, the, premature, and, ectopic, expression, of, early, endothelial, and, blood, differentiation, genes, such, as, 'fli1,', flk1, and, 'gata1,', indicating, that, 'Hhex', can, positively, regulate, endothelial, and, blood, differentiation])]). relacion([sujeto(['However,', analysis, of, a, hhex, deficiency, allele, shows, that, hhex, is, not, essential, for, early, endothelial, and, blood, 'differentiation,']), verbo([suggesting]), complemento([that, another, 'gene,', perhaps, 'scl,', compensates, for, the, absence, of, 'Hhex', function])]). relacion([sujeto(['Furthermore,', we]), verbo([find]), complemento([that, hhex, and, scl, can, induce, each, 'other\'s', 'expression,', suggesting, that, these, two, genes, 'cross-regulate', each, other, during, early, endothelial, and, blood, differentiation])]). relacion([sujeto(['Together,', these, data]), verbo([provide]), complemento([the, initial, framework, of, a, pathway, that, can, be, used, to, further, integrate, the, molecular, events, regulating, hemangioblast, differentiation])]). relacion([sujeto(['In', a, previous, 'study,', it, was, demonstrated, that, 'Ras', activation, was]), verbo([involved]), complemento([in, 'thrombopoietin-induced', megakaryocytic, differentiation])]). relacion([sujeto(['However,', the, introduction, of, 'GATA-1']), verbo([led]), complemento([to, reprogramming, of, 32, 'D', cl3, toward, 'erythrocytic/megakaryocytic', lineage, and, enabled, it, to, undergo, megakaryocytic, differentiation, in, response, to, 'H-ras(G12V)'])]). relacion([sujeto(['Endogenous', 'GATA-1', activities, were, markedly]), verbo([suppressed]), complemento([in, 'PU'])]). relacion([sujeto([1, were]), verbo([found]), complemento([to, associate, through, their, 'DNA-binding', domains, and, to, inhibit, the, respective, 'DNA-binding', activities, of, each, other])]). relacion([sujeto(['In', 'addition,', 'c-Myb']), verbo([bound]), complemento([to, 'GATA-1', and, inhibited, its, 'DNA-binding', activities])]). relacion([sujeto([1, that]), verbo([retained]), complemento([their, own, transcriptional, activities, but, could, not, inhibit, the, reciprocal, partner, were, less, effective, in, changing, the, lineage, phenotype, of, 32, 'D', cl3, and, 'K562'])]). relacion([sujeto(['These', results]), verbo([suggested]), complemento([that, 'GATA-1', activities, may, be, crucial, for, 'Ras-mediated', megakaryocytic, differentiation, and, that, its, activities, may, be, regulated, by, the, direct, interaction, with, other, 'lineage-specific', transcription, factors, such, as, 'PU'])]). relacion([sujeto(['Induction', of, specific, gene, expression, may]), verbo([provide]), complemento([an, alternative, or, a, support, to, conventional, cytotoxic, chemotherapy, of, 'cancer,', as, well, as, to, therapy, for, sickle, cell, diseases])]). relacion([sujeto(['Erythroid', differentiation, and, inhibition, of, proliferation, of, the, human, 'CML', 'K562', cell, line, was]), verbo([induced]), complemento([by, guanosine, 5, '\'', -, triphosphate, '(', 'GTP)'])]). relacion([sujeto(['The', hemoglobin, production, in, cells, was, correlated, to, an]), verbo([increase]), complemento([in, 'alpha-', and, 'gamma-globin', mRNA, expression])]). relacion([sujeto(['At', the, transcriptional, 'level,', we, showed, that, both, the, expression, of, the, major, erythroid, transcription, factor, 'GATA-1', '(', protein, and, 'mRNA)', and, its]), verbo([binding]), complemento([capacity, to, the, 'gamma-globin', gene, promoter, was, transiently, increased])]). relacion([sujeto(['Moreover,', 'GTP', moderately]), verbo([stimulated]), complemento([the, 'gamma-globin', gene, promoter, after, 48, h, of, treatment])]). relacion([sujeto(['At', the, 'post-transcriptional', 'level,', 'GTP', treatment]), verbo([led]), complemento([to, a, drastic, increase, of, the, 'gamma-globin', mRNA, 'half-life'])]). relacion([sujeto(['This', stabilizing, effect, of, 'GTP', was]), verbo([mediated]), complemento([via, the, 3, '\'', -, untranslated, region, '(', 3, '\'', -, 'UTR)', of, the, 'gamma-globin', mRNA])]). relacion([sujeto(['Here', we, show, that, overexpression, of, 'GATA-1', in, erythroid, cells]), verbo([inhibits]), complemento([their, 'differentiation,', leading, to, a, lethal, anaemia])]). relacion([sujeto(['Gel', shift, experiments, show, 'that,', although, the, murine, and, the, human, 'GATA', sequences, both]), verbo([bind]), complemento(['GATA-1,', the, murine, sequence, alone, forms, an, additional, complex, '(', 'B)', not, detected, with, the, human, sequence])]). relacion([sujeto(['A', 'G', nucleotide, 3, to, 'GATA', appears, crucial, because, its, substitution, abrogates, 'B', but, not, 'GATA-1']), verbo([binding]), complemento([and, restores, megakaryocyte, specificity, to, the, murine, promoter])]). relacion([sujeto(['Conversely,', substitution, of, the, human, 'GATA-1']), verbo([binding]), complemento([sequence, by, its, murine, homologue, that, binds, both, 'GATA-1', and, complex, 'B', induces, an, abnormal, activity, for, the, human, promoter, in, 'K562', cells])]). relacion([sujeto(['Altogether,', our, data]), verbo([suggest]), complemento([that, limited, changes, in, the, 'GATA-containing', enhancer, of, the, 'GPIIb', promoter, can, induce, the, recruitment, of, accessory, proteins, that, could, be, involved, in, alteration, of, a, 'megakaryocyte-restricted', gene, activation, program])]). relacion([sujeto(['Band', shift, experiments, show, that, the, 'GATA-1', protein]), verbo([binds]), complemento([to, both, 5, a, and, the, mutant, 5, a, and, forms, a, large, protein, complex])]). relacion([sujeto(['Together,', the, results]), verbo([suggest]), complemento([that, 'GATA-1', bound, at, 5, a, is, a, 'strong,', proximal, repressor, of, 'HS2', enhancer, activity])]). relacion([sujeto(['We']), verbo([have]), complemento([investigated, the, ability, of, 'double-stranded', 'RNA', '(', 'dsRNA)', to, inhibit, gene, expression, in, a, 'vertebrate,', the, 'zebrafish,', 'Danio', rerio])]). relacion([sujeto(['Injection', of, dsRNA, corresponding, to, the, 'T-box', gene, 'tbx16/spadetail', '(', 'spt)', into, early, 'wild-type', embryos]), verbo([caused]), complemento([a, rapid, and, dramatic, loss, of, 'tbx16/spt', mRNA, in, the, blastula])]). relacion([sujeto(['The', 'DNA']), verbo([binding]), complemento([domain, of, 'GATA-1', consists, of, two, adjacent, homologous, zinc, 'fingers,', of, which, only, the, 'C-terminal', finger, binds, 'DNA', independently])]). relacion([sujeto(['Solution', structure, studies]), verbo([have]), complemento([shown, that, the, 'DNA', is, bent, by, about, 15, degrees, in, the, complex, formed, with, the, single, 'C-terminal', finger, of, 'GATA-1'])]). relacion([sujeto(['The', 'N-terminal', finger, stabilizes, 'DNA']), verbo([binding]), complemento([at, some, sites])]). relacion([sujeto(['To', determine, whether, it, contributes, to, 'DNA', 'bending,', we]), verbo([have]), complemento([performed, circular, permutation, 'DNA', bending, experiments, with, a, variety, of, 'DNA-binding', sites, recognized, by, 'GATA-1'])]). relacion([sujeto(['We', propose, that, the, 'N-', and, 'C-terminal', fingers, of, 'GATA-1', adopt, different, orientations, when]), verbo([bound]), complemento([to, different, cognate, 'DNA', sites])]). relacion([sujeto(['GATA-1', and, other, vertebrate, 'GATA', factors, contain, a, 'DNA']), verbo([binding]), complemento([domain, composed, of, two, adjacent, homologous, zinc, fingers])]). relacion([sujeto(['Whereas', only, the, 'C-terminal', finger, of, 'GATA-1', is, capable, of, independent]), verbo([binding]), complemento([to, the, 'GATA', recognition, 'sequence,', double, 'GATA', sites, that, require, both, fingers, for, high, affinity, interaction, are, found, in, several, genes])]). relacion([sujeto(['We', propose, a, mechanism, whereby, adjacent, zinc, fingers]), verbo([interact]), complemento([to, influence, the, binding, and, transactivation, properties, of, 'GATA-1', at, a, subset, of, 'DNA-binding', sites])]). relacion([sujeto(['By', using, two, such, double, 'GATA', sites, we, demonstrate, that, the, 'N-terminal', finger, and, adjacent, linker, region, can, alter, the]), verbo([binding]), complemento([specificity, of, the, 'C-terminal', finger, sufficiently, to, prevent, it, from, recognizing, some, consensus, 'GATA', sequences])]). relacion([sujeto(['Therefore,', the, two, zinc, fingers, form, a, composite]), verbo([binding]), complemento([domain, having, a, different, 'DNA', binding, specificity, from, that, shown, by, the, constituent, single, 'C-terminal', finger])]). relacion([sujeto(['Furthermore,', we, compare, two, of, these, double, sites, and, show, that, high, affinity]), verbo([binding]), complemento([of, 'GATA-1', to, a, reporter, gene, does, not, necessarily, induce, 'transactivation,', namely, the, sequence, of, the, 'DNA-binding', site, can, alter, the, ability, of, 'GATA-1', to, stimulate, transcription])]). relacion([sujeto(['GATA-binding', sites, are, consistently]), verbo([found]), complemento([in, promoters, or, enhancers, of, genes, expressed, selectively, in, erythroid, cells])]). relacion([sujeto(['By', subtractive, 'analysis,', we, identified, a, new, 'ATP-binding', cassette, '(', 'ABC)', transporter, that, is, strongly, and, rapidly]), verbo([induced]), complemento([by, 'GATA-1'])]). relacion([sujeto(['This', 'protein,', named, 'ABC-me', '(', for, 'ABC-mitochondrial', 'erythroid),', localizes, to, the, mitochondrial, inner, membrane, and, is]), verbo([expressed]), complemento([at, particularly, high, levels, in, erythroid, tissues, of, embryos, and, adults])]). relacion([sujeto(['ABC-me', is]), verbo([induced]), complemento([during, erythroid, maturation, in, cell, lines, and, primary, hematopoietic, 'cells,', and, its, overexpression, enhances, hemoglobin, synthesis, in, erythroleukemia, cells])]). relacion([sujeto(['The', 'ABC', proteins]), verbo([participate]), complemento([in, diverse, physiological, processes, by, coupling, 'ATP', hydrolysis, to, the, transport, of, a, variety, of, substrates, across, cell, membranes])]). relacion([sujeto(['We', speculate, that, 'ABC-me,', a, newly, identified, 'erythroid-expressed', 'ABC', superfamily, 'member,', may]), verbo([mediate]), complemento([critical, mitochondrial, transport, functions, related, to, heme, biosynthesis])]). relacion([sujeto(['Anti-Müllerian', hormone, '(', 'AMH),', also, known, as, 'Müllerian']), verbo([inhibiting]), complemento([substance, '(', 'MIS),', is, one, of, the, earliest, and, 'best-known', markers, of, 'Sertoli', cell, differentiation, and, is, expressed, until, around, puberty])]). relacion([sujeto(['The', present, study, is, aimed, at, the, better, understanding, of, the, molecular, pathways]), verbo([involved]), complemento([in, testicular, development, and, establishment, of, adult, functions, with, regards, to, 'AMH', regulation])]). relacion([sujeto(['We', 'found,', within, the, mouse, 'AMH', 'promoter,', putative, 'GATA', motifs, '(', 'A/T)GATA(A/G),', known, to, be, specifically]), verbo([bound]), complemento([by, members, of, the, 'GATA', transcription, factor, family])]). relacion([sujeto(['We', then, carried, out, 'RNase', protection, assays, and, immunohistochemical, techniques, aimed, at, comparing, precisely, the, chronological, expression, patterns, of, 'AMH', and, 'GATA-1,', this, latter, being]), verbo([expressed]), complemento([in, the, testis, after, birth])]). relacion([sujeto(['Using', both, approaches, we]), verbo([found]), complemento([an, inverse, and, close, relationship, between, 'AMH', and, 'GATA-1', mRNA, and, protein, expression, during, the, 'pre-pubertal', period])]). relacion([sujeto(['These', results, allowed, us, to, define, a, transitory, 4, -, 5, -, day, 'period,', starting, from, 3, dpp, when, both, proteins, are, heterogeneously]), verbo([expressed]), complemento([in, 'Sertoli', cells, and, showed, that, the, appearance, of, 'GATA-1', is, associated, with, the, decrease, of, 'AMH', expression, in, these, cells])]). relacion([sujeto(['Furthermore', 'DNA-protein', interaction, in, in, vitro, studies, showed, first, that, 'GATA-1']), verbo([binds]), complemento([with, various, affinities, on, sites, found, in, the, 'AMH', promoter, and, second, that, the, proximity, of, the, two, strongest, affinity, sites, leads, to, a, synergistic, binding, effect])]). relacion([sujeto(['Altogether,', the, present, study]), verbo([suggests]), complemento([that, 'GATA-1', participates, in, 'AMH', gene, repression, during, the, 'pre-pubertal', period])]). relacion([sujeto(['The', zinc, finger, protein, 'GATA-1', functions, in, a, 'concentration-dependent', fashion, to]), verbo([activate]), complemento([the, transcription, of, erythroid, and, megakaryocytic, genes])]). relacion([sujeto(['Less', is, 'understood,', 'however,', regarding, factors, that]), verbo([regulate]), complemento([the, 'GATA-1', gene])]). relacion([sujeto([8, -, 'Luc)', the, deletion, of, a, central, subdomain, of, intron, 1]), verbo([inhibited]), complemento([transcription, &, 'gt;/=10-fold', in, transiently, transfected, erythroid, 'SKT6', 'cells,', and, likewise, inhibited, 'high-level', transcription, in, erythroid, 'FDCW2ER-GATA1', cells])]). relacion([sujeto(['Within', intron, 1, ',', repeated, 'GATA', and, 'Ap1', consensus, elements, in, a, central, region, are, described, which, when, linked, directly, to, reporter, cassettes]), verbo([promote]), complemento([transcription, in, erythroid, 'SKT6', and, 'FDCER-GATA1', cells, at, high, rates])]). relacion([sujeto(['Moreover,', 'GATA-1']), verbo([activated]), complemento([transcription, from, this, subdomain, in, 293, 'cells,', and, in, 'SKT6', cells, this, subdomain, footprinted, in, vivo])]). relacion([sujeto([8, -, 'pEGFP;', activity, was]), verbo([decreased]), complemento([by, 43, and, 56, '%', ',', 'respectively,', by, the, deletion, of, either, 'motif;', and, the, above, 1800, -, base, pair, region, of, intron, 1, per, se, was, transcribed, at, rates, uniformly, greater, than, 'G6'])]). relacion([sujeto(['GATA4', is, a, transcriptional, activator, of, 'cardiac-restricted', promoters, and, is]), verbo([required]), complemento([for, normal, cardiac, morphogenesis])]). relacion([sujeto(['Friend', of, 'GATA-2', '(', 'FOG-2)', is, a, multizinc, finger, protein, that]), verbo([associates]), complemento([with, 'GATA4', and, represses, 'GATA4-dependent', transcription])]). relacion([sujeto(['The', results, demonstrated, that, 1, ')', zinc, fingers, 1, and, 6, of, 'FOG-2', are, each, capable, of]), verbo([interacting]), complemento([with, evolutionarily, conserved, motifs, within, the, 'N-terminal', zinc, finger, of, mammalian, 'GATA', 'proteins,', 2, ')', a, nuclear, localization, signal, '(', 'RKRRK)', '(', amino, acids, 736, -, 740, ')', is, required, to, program, nuclear, targeting, of, 'FOG-2,', and, 3, ')', 'FOG-2', can, interact, with, the, transcriptional, 'co-repressor,', 'C-terminal-binding', 'protein-2', via, a, conserved, sequence, motif, in, 'FOG-2', '(', 'PIDLS)'])]). relacion([sujeto(['Surprisingly,', 'however,', this, interaction, with, 'C-terminal-binding', 'protein-2', is, not]), verbo([required]), complemento([for, 'FOG-2-mediated', repression, of, 'GATA4-dependent', transcription])]). relacion([sujeto(['Instead,', we]), verbo([have]), complemento([identified, a, novel, 'N-terminal', domain, of, 'FOG-2', '(', amino, acids, 1, -, 247, ')', that, is, both, necessary, and, sufficient, to, repress, 'GATA4-dependent', transcription])]). relacion([sujeto(['This', 'N-terminal', repressor, domain, is, functionally]), verbo([conserved]), complemento([in, the, related, 'protein,', 'Friend', of, 'GATA1'])]). relacion([sujeto(['Taken', 'together,', these, results, define, a, set, of, evolutionarily]), verbo([conserved]), complemento([mechanisms, by, which, 'FOG', proteins, repress, 'GATA-dependent', transcription, and, thereby, form, the, foundation, for, genetic, studies, designed, to, elucidate, the, role, of, 'FOG-2', in, cardiac, development])]). relacion([sujeto(['The', 'Notch', signal, transduction, pathway, is, a, highly]), verbo([conserved]), complemento([regulatory, system, that, controls, multiple, developmental, processes])]). relacion([sujeto(['We']), verbo([have]), complemento([established, an, erythroleukemia, cell, model, to, study, how, 'Notch', regulates, cell, fate, and, erythroleukemic, cell, differentiation])]). relacion([sujeto(['K562', and, 'HEL', cells]), verbo([expressed]), complemento([the, 'Notch-1', receptor, and, the, 'Notch', ligand, 'Jagged-1'])]). relacion([sujeto(['The', stable, expression, of, the, constitutively, active, intracellular, domain, of, 'Notch-1', '(', 'NIC-1)', in, 'K562', cells]), verbo([inhibited]), complemento([erythroid, without, affecting, megakaryocytic, maturation])]). relacion([sujeto(['Expression', of, antisense, 'Notch-1']), verbo([induced]), complemento([spontaneous, erythroid, maturation])]). relacion([sujeto(['Microarray', gene, expression, analysis, identified, genes]), verbo([activated]), complemento([during, erythroid, 'maturation,', and, 'NIC-1', disrupted, the, 'maturation-dependent', changes, in, the, expression, of, these, genes])]). relacion([sujeto(['These', results, show, that, 'NIC-1', alters, the, pattern, of, gene, expression, in, 'K562', cells]), verbo([leading]), complemento([to, a, block, in, erythroid, maturation, and, therefore, suggest, that, 'Notch', signaling, may, control, the, developmental, potential, of, normal, and, malignant, erythroid, progenitor, cells])]). relacion([sujeto(['The', 'erythroid-enriched', transcription, factor, 'NF-E2', is, composed, of, two, 'subunits,', p45, and, 'p18,', the, former, of, which, is, mainly]), verbo([expressed]), complemento([in, the, hematopoietic, system])]). relacion([sujeto(['We']), verbo([have]), complemento([isolated, and, characterized, the, mouse, p45, 'NF-E2', 'gene;', we, show, here, 'that,', similar, to, the, human, 'gene,', the, mouse, gene, has, two, alternative, 'promoters,', which, are, differentially, active, during, development, and, in, different, hematopoietic, cells])]). relacion([sujeto(['Transfection', experiments, show, that, proximal, promoter, 1, b]), verbo([has]), complemento([a, strong, activity, in, erythroid, 'cells,', which, is, completely, dependent, on, the, integrity, of, a, palindromic, 'GATA-1', binding, site])]). relacion([sujeto(['When', the, promoter, 1, b, is, placed, 3, '\'', to, the, promoter, 1, a, and, reporter, 'gene,', in, an, arrangement, that, resembles, the, natural, 'one,', it]), verbo([acts]), complemento([as, an, enhancer, to, stimulate, the, activity, of, the, upstream, promoter, la])]). relacion([sujeto(['The', glycoprotein, 'gp91(phox)', is, an, essential, component, of, the, phagocyte, 'NADPH', oxidase, and, is]), verbo([expressed]), complemento([in, 'eosinophils,', 'neutrophils,', 'monocytes,', and, 'B-lymphocytes'])]). relacion([sujeto(['We', previously]), verbo([suggested]), complemento([an, 'eosinophil-specific', mechanism, of, 'gp91(phox)', gene, expression])]). relacion([sujeto(['A', 10, -, base, pair, '(', 'bp)', region, from, bp, -, 105, to, -, 96, of, the, promoter]), verbo([activated]), complemento([transcription, of, the, gene, in, eosinophilic, 'cells,', but, not, in, 'neutrophilic,', 'monocytic,', or, 'B-lymphocytic', cells])]). relacion([sujeto(['Gel', shift, assays, using, a, 'GATA', competitor, and, specific, antibodies, demonstrated, that, both, 'GATA-1', and, 'GATA-2', specifically]), verbo([bound]), complemento([to, the, -, 98, 'GATA', site, with, similar, affinities])]). relacion([sujeto(['Individual', transfection, of, 'GATA-1', and, 'GATA-2', into, 'Jurkat', 'cells,', which]), verbo([have]), complemento([neither, endogenous, 'GATA-1', nor, 'GATA-2,', activated, the, -, 105, /, +, 12, construct, in, a, -, 98, 'GATA', 'site-dependent', manner])]). relacion([sujeto(['Combined', transfection, of, 'GATA-1', and, 'GATA-2']), verbo([activated]), complemento([the, promoter, less, than, transfection, of, 'GATA-1', alone])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, 'GATA-1', is, an, activator, and, that, 'GATA-2', is, a, relative, competitive, inhibitor, of, 'GATA-1', in, the, expression, of, the, 'gp91(phox)', gene, in, human, eosinophils])]). relacion([sujeto(['Haematopoietic', development, is]), verbo([regulated]), complemento([by, nuclear, protein, complexes, that, coordinate, 'lineage-specific', patterns, of, gene, expression])]). relacion([sujeto(['Targeted', mutagenesis, in, embryonic, stem, cells, and, mice]), verbo([has]), complemento([revealed, roles, for, the, 'X-linked', gene, 'Gata1', in, erythrocyte, and, megakaryocyte, differentiation])]). relacion([sujeto(['GATA-1', is, the, founding, member, of, a, family, of, 'DNA-binding', proteins, that]), verbo([recognize]), complemento([the, motif, 'WGATAR', through, a, conserved, multifunctional, domain, consisting, of, two, 'C4-type', zinc, fingers])]). relacion([sujeto(['This', highly]), verbo([conserved]), complemento([valine, is, necessary, for, interaction, of, the, 'amino-terminal', zinc, finger, of, 'GATA-1', with, its, essential, 'cofactor,', 'FOG-1', '(', for, friend, of, 'GATA-1;', refs, 9, -, 12, ')'])]). relacion([sujeto(['We', show, that, the, 'V205M', mutation, abrogates, the, interaction, between, 'Gata-1', and, 'Fog-1,']), verbo([inhibiting]), complemento([the, ability, of, 'Gata-1', to, rescue, erythroid, differentiation, in, an, erythroid, cell, line, deficient, for, 'Gata-1', '(', 'G1E)'])]). relacion([sujeto(['Our', findings, underscore, the, importance, of, 'FOG-1:Gata-1', associations, in, both, megakaryocyte, and, erythroid, 'development,', and]), verbo([suggest]), complemento([that, other, 'X-linked', anaemias, or, thrombocytopenias, may, be, caused, by, defects, in, 'GATA1'])]). relacion([sujeto(['This', zinc, finger, transcription, factor, is]), verbo([required]), complemento([for, expression, of, the, adult, beta, globin, 'gene,', and, it, has, been, suggested, that, it, plays, an, important, role, in, the, developmental, switch, from, fetal, gamma, to, adult, beta, globin, gene, expression])]). relacion([sujeto(['We']), verbo([have]), complemento([previously, described, a, sequence, element, in, the, distal, promoter, region, of, the, mouse, 'EKLF', gene, that, is, critical, for, the, expression, of, this, transcription, factor])]). relacion([sujeto(['The', element, consists, of, an, 'E', box, motif, flanked, by, 2, 'GATA-1']), verbo([binding]), complemento([sites])]). relacion([sujeto([2000, ;, 95, :, 1652, -, 1655, ')', 'Cytokines', exert, pleiotropic, effects, on]), verbo([target]), complemento([cells, in, a, manner, dependent, on, the, cell, type, or, stage, of, differentiation])]). relacion([sujeto(['During', 'IL-6-induced', macrophage, differentiation, of, 'M1', 'cells,', 'IL-6', 'down-regulated', cyclin, 'D1', expression, and]), verbo([induced]), complemento(['p19(INK4D)', 'expression,', leading, to, reduction, in, cdk4, activities])]). relacion([sujeto(['Both', 'IL-6-induced', macrophage, differentiation, and, apoptosis, were, significantly, abrogated, by, coexpression, of, cyclin, 'D1', and, 'bcl-2,', whereas, overexpressions, of, cyclin, 'D1', or, 'bcl-2']), verbo([inhibited]), complemento([only, differentiation, or, 'apoptosis,', respectively])]). relacion([sujeto(['These', results]), verbo([suggested]), complemento([that, 'GATA-1', may, not, only, reprogram, the, lineage, phenotype, of, 'M1', cells, but, also, disrupt, the, biologic, effects, of, 'IL-6', through, the, sustained, expression, of, cyclin, 'D1', and, 'bcl-2'])]). relacion([sujeto(['At', a, clinically, relevant, concentration, of, 1, 'microM,', 'AZT']), verbo([inhibited]), complemento([specifically, erythroid, cell, growth, by, approximately, 58, '%', as, compared, with, untreated, cells])]). relacion([sujeto(['The', percentage, of, cells, synthesizing, hemoglobin, was]), verbo([decreased]), complemento([also, by, 47, '%', in, 'AZT-treated', cells, with, 'beta-globin', mRNA, levels, accounting, for, 0.27, pmol, in, treated, cells, as, compared, with, 1.44, under, control, conditions, while, 'beta-actin', levels, remained, unchanged])]). relacion([sujeto(['Under', the, same, 'conditions,', 'AZT']), verbo([inhibited]), complemento([the, 'beta-globin', chain, synthesis, by, approximately, 60, '%', as, compared, with, the, control])]). relacion([sujeto(['Consistent', with, the, data, described, above, was, the]), verbo([finding]), complemento([that, a, concentration, as, low, as, 0.1, microM, of, 'AZT', decreased, by, almost, 40, '%', the, binding, level, of, the, 'erythroid-specific', transcription, factor, 'GATA-1'])]). relacion([sujeto(['These', findings, demonstrate, that, 'AZT,', at, clinical, relevant, 'concentrations,', specifically]), verbo([inhibits]), complemento(['beta-globin', gene, expression, in, human, erythroid, progenitor, liquid, cell, culture])]). relacion([sujeto(['Transcripts', with, 5, '\'', -, 'UTR', exon, 1, 'A', alone, or, fused, to, exon, 1, 'B', were, ubiquitously]), verbo([expressed]), complemento(['(', 'housekeeping),', whereas, transcripts, with, 5, '\'', -, 'UTR', exon, 2, 'A', were, only, present, in, erythroid, cells, '(', 'erythroid-specific)'])]). relacion([sujeto(['Analysis', of, the, 'TATA-less', housekeeping, promoter, upstream, of, exon, 1, 'A', revealed]), verbo([binding]), complemento([sites, for, ubiquitously, expressed, transcription, factors, 'Sp1,', 'NF1,', 'AP1,', 'Oct1,', and, 'NRF2'])]). relacion([sujeto(['The', 'TATA-less', 'erythroid-specific', promoter, upstream, of, exon, 2, 'A', had, nine, putative, 'GATA1', erythroid, enhancer]), verbo([binding]), complemento([sites])]). relacion([sujeto(['Site-specific', mutagenesis, of, the, first, 'GATA1']), verbo([binding]), complemento([site, markedly, reduced, luciferase, activity, in, 'K562', cells, '(', &, 'lt;5%', of, wild, 'type)'])]). relacion([sujeto(['Thus,', housekeeping, and, 'erythroid-specific', transcripts, are]), verbo([expressed]), complemento([from, alternative, promoters, of, a, single, mouse, 'URO-synthase', gene])]). relacion([sujeto(['Gene']), verbo([targeting]), complemento([experiments, have, revealed, that, transcription, factors, such, as, 'c-Myb', and, 'GATA-1', play, crucial, roles, during, hematopoietic, differentiation])]). relacion([sujeto(['In', 'addition,', 'CREB-binding', protein, '(', 'CBP)']), verbo([acts]), complemento([as, a, transcriptional, adapter, for, various, transcription, 'factors,', including, 'c-Myb', and, 'GATA-1'])]). relacion([sujeto(['In', this, 'paper,', we, show, that, the, transcription, factors, 'c-Myb', and, 'GATA-1', each]), verbo([inhibit]), complemento([the, transcriptional, activity, of, the, other, and, that, any, possible, bipartite, complexes, 'c-Myb,', 'GATA-1,', and, 'CBP', could, be, 'formed,', but, the, tripartite, complex, was, hardly, formed])]). relacion([sujeto(['The', exclusive]), verbo([binding]), complemento([of, 'GATA-1', and, 'c-Myb', to, 'CBP', is, probably, the, molecular, basis, for, the, mutual, inhibition, of, their, transcriptional, activity])]). relacion([sujeto(['Our', data]), verbo([suggest]), complemento([that, 'cross-talk', between, these, three, factors, might, be, important, for, hematopoietic, differentiation, and, that, 'CBP', functions, as, a, key, molecule, during, the, process])]). relacion([sujeto(['In', transfection, 'analyses,', this, region]), verbo([activated]), complemento([reporter, gene, expression, from, an, artificial, promoter, in, a, 'position-', and, 'orientation-independent', 'manner,', indicating, that, the, region, functions, as, the, 'GATA-1', gene, hematopoietic, enhancer, '(', 'G1HE)'])]). relacion([sujeto(['However,', when, analyzed, in, transgenic, embryos, in, 'vivo,', 'G1HE', activity, was, orientation, dependent, and, also]), verbo([required]), complemento([the, presence, of, the, endogenous, 'GATA-1', gene, hematopoietic, promoter])]). relacion([sujeto(['We', show, that, 'G1HE', contains, a, 149, -, bp, core, region, which, is, critical, for, 'GATA-1', gene, expression, in, both, primitive, and, definitive, erythroid, cells, but, that, expression, in, megakaryocytes]), verbo([requires]), complemento([the, core, plus, additional, sequences, from, 'G1HE'])]). relacion([sujeto(['These', results, thus, demonstrate, the, presence, of, a, critical, network, of, 'GATA', factors, and, 'GATA']), verbo([binding]), complemento([sites, that, controls, the, expression, of, this, gene])]). relacion([sujeto(['A', systemic, approach, is, 'proposed,', which, makes, it, possible, to]), verbo([increase]), complemento([the, accuracy, of, recognition, of, functional, sites, in, arbitrary, 'DNA', sequences])]). relacion([sujeto(['The', approach, was, used, to, study, the]), verbo([binding]), complemento([sites, of, 'GATA-1', and, 'C/EBP', transcription, factors])]). relacion([sujeto(['It', was]), verbo([found]), complemento([that, the, averaged, recognition, of, these, sites, is, more, precise, than, each, of, specific, 'recognitions,', which, just, follows, from, the, 'Central', limit, theorem])]). relacion([sujeto(['The', 'beta-globin', locus, control, region, '(', 'LCR)', is, a, cis, regulatory, element, that, is, located, in, the, 5, '\'', part, of, the, locus, and]), verbo([confers]), complemento(['high-level', erythroid, 'lineage-specific', and, 'position-independent', expression, of, the, globin, genes])]). relacion([sujeto(['To']), verbo([gain]), complemento([insights, into, its, 'function,', mouse, 'HS5', was, cloned, and, sequenced])]). relacion([sujeto(['Comparison', of, the, 'HS5', sequences, of, 'mouse,', 'human,', and, galago, revealed, two, extensively]), verbo([conserved]), complemento(['regions,', designated, 'HS5A', and, 'HS5B'])]). relacion([sujeto(['The', positions, of, each, of, these, 'HSs', colocalize, with, either, 'GATA-1', or, 'Ap1/NF-E2', 'motifs,']), verbo([suggesting]), complemento([that, these, protein, binding, sites, are, implicated, in, the, formation, of, 'HS5'])]). relacion([sujeto(['Gel', retardation, assays, indicated, that, the, 'Ap1/NF-E2', motifs, identified, in, murine, 'HS5A', and, 'HS5B']), verbo([interact]), complemento([with, 'NF-E2', or, similar, proteins])]). relacion([sujeto(['HS5', was, detected, in, murine, brain, but, not, in, murine, kidney, or, adult, 'liver,']), verbo([suggesting]), complemento([that, this, site, is, not, ubiquitous])]). relacion([sujeto(['The', presence, of, 'GATA-1', and, 'NF-E2', motifs, '(', which, are, common, features, of, the, 'DNase', 'I', hypersensitive, sites, of, the, 'LCR)']), verbo([suggests]), complemento([that, the, 'HS5', is, organized, in, a, manner, similar, to, that, of, the, other, 'HSs'])]). relacion([sujeto(['Taken', 'together,', our, results]), verbo([suggest]), complemento([that, 'HS5', is, an, inherent, component, of, the, 'beta-globin', locus, control, region])]). relacion([sujeto(['Fli-1', is, a, 'proto-oncogene', which, is, rearranged, in, tumors]), verbo([induced]), complemento([by, three, different, 'retroviruses,', 'Cas-Br-E,', 'F-MuLV,', and, 10, 'A1'])]). relacion([sujeto(['This', gene, is, a, member, of, the, 'Ets', gene, 'family,', a, class, of, transcription, factors, that]), verbo([recognize]), complemento([and, bind, to, a, 'DNA', motif, known, as, the, 'Ets', binding, site, '(', 'EBS)'])]). relacion([sujeto(['Our', laboratory]), verbo([has]), complemento([previously, cloned, and, characterized, the, promoter, region, of, both, human, and, mouse, 'Fli-1', genes])]). relacion([sujeto(['We', had, then, identified, several, regulatory, elements]), verbo([conserved]), complemento([between, the, two, species])]). relacion([sujeto(['EMSA', analysis, performed, with]), verbo([nuclear]), complemento([extracts, from, different, cell, lines, showed, that, the, 'EBS', element, in, intron, 1, '(', 'EBSi)', was, bound, by, one, potential, 'Ets-related', ubiquitous, factor])]). relacion([sujeto(['The', 'GATA/EBS', element, was]), verbo([bound]), complemento([by, several, factors, that, seemed, 'Ets-related,', one, of, which, was, found, to, be, specifically, expressed, in, hematopoietic, cells])]). relacion([sujeto(['A', human, 'Fli-1-derived', genomic, fragment, containing, the, 'GATA/EBS']), verbo([led]), complemento([to, enhanced, transcription, when, positioned, upstream, of, the, 'SV40', promoter, in, the, erythroleukemic, 'HEL', cell, line])]). relacion([sujeto(['In', 'addition,', an]), verbo([increasing]), complemento([number, of, 'GATA/EBS', oligonucleotides, upstream, of, this, same, promoter, resulted, in, a, copy, 'number-dependent', increase, in, luciferase, activity, which, was, greatly, reduced, when, the, 'EBS', consensus, sequence, was, mutated])]). relacion([sujeto(['One', of, the, factors]), verbo([binding]), complemento([to, the, 'GATA/EBS', region, was, identified, to, be, 'Spi-1', by, supershift, analysis, and, was, also, shown, to, bind, to, the, 'EBS', element, of, the, human, 'Ets-2', gene])]). relacion([sujeto(['Supershift', analysis, also, demonstrated, the]), verbo([binding]), complemento([of, the, 'GATA-1', factor, to, the, 'GATA/EBS', dual, element])]). relacion([sujeto(['Our', results]), verbo([suggest]), complemento([that, 'Spi-1', and, 'GATA-1', might, play, a, key, role, in, the, regulation, of, 'Fli-1'])]). relacion([sujeto(['Activation', of, globin, genes, during, development, is, accompanied, by, localized, alterations, of, chromatin, 'structure,', and, 'CACCC']), verbo([binding]), complemento([factors, and, 'GATA-1,', which, interact, with, both, globin, promoters, and, the, 'LCR,', are, believed, to, be, critical, for, globin, gene, transcription, activation])]). relacion([sujeto(['We']), verbo([found]), complemento([that, an, 'HS2', element, mutated, in, its, 'GATA', motif, failed, to, remodel, the, 'epsilon-globin', promoter, or, activate, transcription, yet, 'HS2', nuclease, accessibility, did, not, change])]). relacion([sujeto(['The', results, indicate, that, the, 'epsilon-globin', promoter, and, 'HS2']), verbo([interact]), complemento([both, structurally, and, functionally, and, that, both, upstream, activators, and, the, basal, transcription, apparatus, contribute, to, the, interaction])]). relacion([sujeto(['The', production, of, red, blood, cells, follows, the, sequential, formation, of, proerythroblasts, and, 'basophilic,', polychromatophilic, and, orthochromatic, 'erythroblasts,', and, is]), verbo([promoted]), complemento([by, the, hormone, erythropoietin, '(', 'Epo)', in, response, to, tissue, hypoxia])]). relacion([sujeto(['Death', receptors, are, a, family, of, surface, molecules, that]), verbo([trigger]), complemento([caspase, activation, and, apoptosis, in, a, variety, of, cell, types])]). relacion([sujeto(['Here', we, show, that, immature, erythroid, cells]), verbo([express]), complemento([several, death, receptors, whose, ligands, are, produced, by, mature, erythroblasts])]). relacion([sujeto(['Exposure', of, erythroid, progenitors, to, mature, erythroblasts, or, 'death-receptor', ligands, resulted, in, 'caspase-mediated', degradation, of, the, transcription, factor, 'GATA-1,', which, is]), verbo([associated]), complemento([with, impaired, erythroblast, development])]). relacion([sujeto(['Expression', of, a, 'caspase-resistant', 'GATA-1', 'mutant,', but, not, of, the, 'wild-type', 'gene,', completely, restored, erythroid, expansion, and, differentiation, following, the]), verbo([triggering]), complemento([of, death, 'receptors,', indicating, that, there, is, regulatory, feedback, between, mature, and, immature, erythroblasts, through, 'caspase-mediated', cleavage, of, 'GATA-1'])]). relacion([sujeto(['Similarly,', erythropoiesis, blockade, following, 'Epo', deprivation, was, largely]), verbo([prevented]), complemento([by, the, expression, of, 'caspase-inhibitory', proteins, or, 'caspase-resistant', 'GATA-1', in, erythroid, progenitors])]). relacion([sujeto(['Gata1', is]), verbo([expressed]), complemento([from, either, one, of, two, alternative, 'promoters,', the, erythroid, '(', proximal, to, the, 'AUG)', and, the, testis, '(', distal, to, the, 'AUG)', 'promoter,', both, used, by, hemopoietic, cells])]). relacion([sujeto(['The', levels, of, total, and, of, 'distal,', but, not, of, 'proximal,', 'Gata1', transcripts]), verbo([increased]), complemento([by, 'five-', to, eightfold, during, in, vivo, and, in, vitro, differentiation, of, 'FVA', and, 'PHZ', cells])]). relacion([sujeto(['The']), verbo([increase]), complemento([in, expression, was, temporally, associated, with, an, increase, in, the, expression, of, 'Eklf,', 'Scl,', and, 'Nfe2,', three, genes, required, for, erythroid, 'differentiation,', and, preceded, by, 24, h, the, repression, of, 'Gata2', and, 'Myb', expression])]). relacion([sujeto(['The', day, 1, 'PHZ', cells, that, survived, 18, h, in, the, absence, of, 'EPO', do, not]), verbo([express]), complemento([globin, genes, and, express, detectable, levels, of, distal, but, not, of, proximal, 'Gata1', transcripts])]). relacion([sujeto(['These', cells]), verbo([activate]), complemento([the, expression, of, the, globin, genes, within, 2, h, when, exposed, to, 'EPO'])]). relacion([sujeto(['Therefore,', during, erythroid, differentiation, of, primary, 'cells,']), verbo([increased]), complemento([expression, of, distal, 'Gata1', transcripts, underlies, the, increase, in, the, expression, of, total, 'Gata1', associated, with, the, establishment, of, the, erythroid, differentiation, program])]). relacion([sujeto(['The', transcription, factor, 'GATA-2', is]), verbo([expressed]), complemento([in, hematopoietic, stem, and, progenitor, cells, and, is, functionally, implicated, in, their, survival, and, proliferation])]). relacion([sujeto(['We']), verbo([have]), complemento([used, estrogen, and, 'tamoxifen-inducible', forms, of, 'GATA-2', to, modulate, the, levels, of, 'GATA-2', in, the, 'IL-3-dependent', multipotential, hematopoietic, progenitor, cell, model, 'FDCP', mix])]). relacion([sujeto(['However,', induction, of, 'GATA-2', activity, in, cells, cultured, in, 'IL-3', blocked, 'factor-dependent', 'self-renewal', but, not, 'factor-dependent', 'survival:', 'Cells', undergo, cell, cycle]), verbo([arrest]), complemento([and, cease, proliferating, but, do, not, apoptose])]). relacion([sujeto(['Differentiation', occurred, in, the, presence, of, 'IL-3', and, did, not]), verbo([require]), complemento([addition, of, exogenous, differentiation, growth, factors, such, as, 'G-CSF', or, 'GM-CSF', normally, required, to, induce, granulomonocytic, differentiation, of, 'FDCP-mix', cells])]). relacion([sujeto(['Conversely,', 'EPO-dependent', erythroid, differentiation, was]), verbo([inhibited]), complemento([by, 'GATA-2', activation])]). relacion([sujeto(['These', biological, effects, were, obtained, with, levels, of, exogenous, 'GATA-2', representing, less, than, twofold]), verbo([increases]), complemento([over, endogenous, 'GATA-2', levels, and, were, not, observed, in, cells, overexpressing, 'GATA-1/ER'])]). relacion([sujeto(['Taken', 'together,', these, data]), verbo([suggest]), complemento([that, threshold, activities, of, 'GATA-2', in, hematopoietic, progenitor, cells, are, a, critical, determinant, in, influencing, 'self-renewal', versus, differentiation, outcomes])]). relacion([sujeto(['The', process, through, which, multipotential, hematopoietic, cells, commit, to, distinct, lineages]), verbo([involves]), complemento([the, induction, of, specific, transcription, factors])]). relacion([sujeto([1, 'Ets', domain, '(', the, winged, 'helix-turn-helix', 'wing)']), verbo([interacts]), complemento([with, the, conserved, 'carboxyl-terminal', zinc, finger, of, 'GATA-1', and, 'GATA-2', and, that, 'GATA', proteins, inhibit, 'PU'])]). relacion([sujeto([1, transactivation, of, critical, myeloid]), verbo([target]), complemento([genes])]). relacion([sujeto(['We', demonstrate, further, that, 'GATA']), verbo([inhibits]), complemento([binding, of, 'PU'])]). relacion([sujeto([1, protein, can]), verbo([inhibit]), complemento([both, 'GATA-1', and, 'GATA-2', transactivation, function])]). relacion([sujeto(['Our', results]), verbo([suggest]), complemento([that, interactions, between, 'PU'])]). relacion([sujeto([2, ')', is, an, important, component, in, the, erythrocyte, membrane, skeletal, network, that]), verbo([regulates]), complemento([the, stability, and, flexibility, of, erythrocytes])]). relacion([sujeto(['Recently,', we]), verbo([provided]), complemento([the, evidence, for, specific, 'P4'])]). relacion([sujeto([2, gene, was]), verbo([found]), complemento([to, be, induced, during, erythroid, differentiation])]). relacion([sujeto([2, promoter, is, 'TATA-less', and, contains, multiple, potential]), verbo([binding]), complemento([sites, for, erythroid, transcription, factors, 'GATA-1,', 'NF-E2,', 'EKLF,', and, 'tal-1/SCL'])]). relacion([sujeto([2, promoter, fused, with, the, luciferase, coding, regions, was]), verbo([induced]), complemento([in, 'DMSO-treated', 'MEL', cells])]). relacion([sujeto([2, promoter, 'DNA', '(', nucleotide, position, -, 88, to, +, 171, relative, to, the, major, transcription, initiation, site, designated, +, 1, ')', ',', containing, a, 'GATA-binding', site, at, position, -, 29, to, -, 24, ',', could, still]), verbo([respond]), complemento([to, the, induction, in, differentiated, 'MEL', cells])]). relacion([sujeto(['Electrophoretic', mobility, shift, assay, revealed, that, 'GATA-1', could]), verbo([bind]), complemento([to, the, -, 29, /, -, 24, 'GATA', motif, and, this, was, confirmed, by, the, observation, that, the, nuclear, protein, bound, to, the, motif, was, supershifted, by, an, 'anti-GATA-1', monoclonal, antibody])]). relacion([sujeto(['Taken', 'together,', these, results]), verbo([suggest]), complemento([that, the, erythroid, transcription, factor, 'GATA-1', plays, an, important, role, in, the, induction, of, 'P4'])]). relacion([sujeto(['Two', 'regions,', -, 74, /, -, 69, and, -, 55, /, -, 47, ',', which, contained]), verbo([binding]), complemento([motifs, for, proteins, belonging, to, the, 'Ets', family, and, the, 'GATA', 'family,', 'respectively,', were, shown, to, be, necessary, for, the, activation, of, the, 'alpha-chain', promoter])]). relacion([sujeto(['Both', the, regulatory, elements]), verbo([enhanced]), complemento([the, promoter, activity, only, in, 'alpha-chain-producing', cells, 'PT18', and, 'RBL-2H3', '(', mast, cell, 'lines),', indicating, that, the, elements, required, specific, 'trans-acting', proteins, present, in, the, 'alpha-chain-producing', cells])]). relacion([sujeto(['EMSA', using]), verbo([nuclear]), complemento([extracts, and, in, 'vitro-translated', proteins, revealed, that, 'Elf-1', and, 'GATA-1', bound, to, the, enhancer, elements])]). relacion([sujeto(['This', is, the, first]), verbo([report]), complemento([describing, the, regulation, in, the, expression, of, the, 'FcepsilonRI', 'alpha-chain'])]). relacion([sujeto(['Here', we]), verbo([report]), complemento([that, in, erythroid, 'cells,', 'GATA-1', strongly, induces, the, expression, of, the, 'anti-apoptotic', protein, 'bcl-xL,', but, not, the, related, proteins, 'bcl-2', and, 'mcl-1'])]). relacion([sujeto(['Consistent', with, a, role, for, 'bcl-xL', in]), verbo([mediating]), complemento(['GATA-1-induced', erythroid, cell, 'survival,', in, 'vitro-differentiated', 'bcl-xL-/-', embryonic, stem, cells, fail, to, generate, viable, mature, definitive, erythroid, 'cells,', a, phenotype, resembling, that, of, 'GATA-1', gene, disruption])]). relacion([sujeto(['In', 'addition,', we, show, that, 'erythropoietin,', which, is, also]), verbo([required]), complemento([for, erythroid, cell, 'survival,', cooperates, with, 'GATA-1', to, stimulate, 'bcl-xL', gene, expression, and, to, maintain, erythroid, cell, viability, during, terminal, maturation])]). relacion([sujeto(['Together,', our, data, show, that, 'bcl-xL', is, essential, for, normal, erythroid, development, and]), verbo([suggest]), complemento([a, regulatory, hierarchy, in, which, 'bcl-xL', is, a, critical, downstream, effector, of, 'GATA-1', and, 'erythropoietin-mediated', signals])]). relacion([sujeto(['Various', strategies]), verbo([led]), complemento([to, the, identification, of, transcription, factors, that, take, part, to, the, control, of, different, steps, during, the, formation, of, new, blood, 'vessels:', the, description, of, the, expression, pattern, of, genes, encoding, these, factors, during, embryonic, development, for, 'ETS-1,', 'ERG', and, 'FLI,', 'SCL/TAL,', 'GATA1', and, 2, ',', the, description, of, the, phenotype, of, embryos, obtained, after, gene, inactivation, by, homologous, recombination, for, 'ARNT', or, 'LKLF,', and, the, study, of, transcriptional, regulation, in, cultured, endothelial, cells, for, 'EGR1', or, 'HOX-D3'])]). relacion([sujeto(['Rather,', factors, controlling, gene, expression]), verbo([induced]), complemento([by, 'hypoxia,', 'shear-stress', or, growth, factors, take, part, in, the, morphogenesis, of, the, vascular, tree])]). relacion([sujeto(['The', study, of, these, factors, may, allow, to, identify, potential, therapeutic]), verbo([targets]), complemento([for, treatments, aimed, at, inhibiting, or, stimulating, the, development, of, new, blood, vessels])]). relacion([sujeto(['The', analysis, of, functional, 'DNA', regulatory, sequences]), verbo([involved]), complemento([in, transcriptional, control, is, critical, to, establishing, which, proteins, mediate, 'cell-specific', gene, expression])]). relacion([sujeto(['As', in, situ]), verbo([binding]), complemento([to, these, sites, is, determined, by, the, accessibility, of, these, regulatory, regions, in, native, chromatin, and, the, availability, of, relevent, 'cell-specific', and, ubiquitous, 'factors,', in, vivo, footprinting, was, used, to, define, protein, 'DNA', interactions, in, human, globin, 'LCRs'])]). relacion([sujeto(['To', further]), verbo([enhance]), complemento([the, detection, of, protein, contacts, with, this, 'technique,', we, have, modified, the, dimethyl, 'sulfate-based', 'ligation-mediated', 'PCR', in, vivo, footprinting, procedure, to, permit, the, assessment, of, protein, binding, at, guanine, and, adenine, 'resides,', rather, than, exclusively, at, guanines])]). relacion([sujeto(['Moreover,', 'GA-LMPCR', in, vivo, footprinting]), verbo([provided]), complemento(['high-resolution', analysis, of, 'AP-1/NF-E2', elements, and, revealed, protein, contacts, at, sequences, that, are, not, coincident, with, previously, described, regulatory, motifs])]). relacion([sujeto(['A', comprehensive, discussion, of, this, modification, and, sample, illustrations, from, our, studies]), verbo([have]), complemento([been, presented, to, demonstrate, the, enhanced, detection, and, resolution, obtained, with, this, procedure])]). relacion([sujeto(['WT1', transcription, is]), verbo([regulated]), complemento([in, erythroid, and, myeloid, lineages, by, the, transcription, factor, 'GATA-1'])]). relacion([sujeto(['K562', was, used, as, reference, positive, control, for, this, cell, line]), verbo([expresses]), complemento([both, 'WT1', and, 'GATA-1'])]). relacion([sujeto(['Among', 'MDS', 'patients,']), verbo([increased]), complemento(['WT1', expression, was, found, in, refractory, anemia, with, excess, blast, '(', 'RAEB)', and, 'RAEB', in, transformation, '(', 'RAEB-T)', subtypes, compared, to, the, normal, 'controls,', whereas, 'WT1', expression, in, refractory, anemia, '(', 'RA)', was, not, different, from, the, normal, control, level])]). relacion([sujeto(['All', of, 'AML', cases, of, subtypes, 'M0,', 'M1,', 'M2', and, 'M3']), verbo([expressed]), complemento(['WT1', more, than, three, times, the, normal, 'WT1', level])]). relacion([sujeto(['Subtypes', 'M4', to, 'M7', showed, significantly, lower, 'WT1', levels, than, 'M1', to, 'M3', and, 'AML', cases, with, 'CD14+']), verbo([expressed]), complemento([less, 'WT1', than, 'CD14-'])]). relacion([sujeto(['Higher', than, normal, 'WT1', levels, were, also]), verbo([expressed]), complemento([in, cases, of, 'ALL'])]). relacion([sujeto(['This', reorganization]), verbo([requires]), complemento([the, globin, locus, control, region, and, is, associated, with, normal, expression, of, the, 'beta-like', globin, genes])]). relacion([sujeto(['To', determine, whether, it, is, possible, to, artificially]), verbo([enhance]), complemento([the, opening, of, the, chromatin, structure, of, a, minimal, 'beta-globin', 'promoter,', we, placed, a, 101, 'bp,', 'erythroid-specific', 'DNase', 1, hypersensitive, 'site-forming', element, '(', 'HSFE)', immediately, upstream, of, the, 'beta-globin', promoter, and, gene])]). relacion([sujeto(['This', element, includes]), verbo([binding]), complemento([sites, for, 'NF-E2,', 'AP-1,', 'GATA-1', and, 'Sp-1'])]). relacion([sujeto(['The', 'HSFE']), verbo([induced]), complemento([an, area, of, enhanced, 'DNase', 1, hypersensitivity, extending, from, the, transcriptional, start, site, to, -, 300, bp, of, the, artificial, promoter, and, significantly, increased, the, proportion, of, 'beta-globin', promoters, in, an, open, chromatin, configuration])]). relacion([sujeto(['This', remodeling, of, promoter, chromatin, structure, resulted, in, 3, -, fold]), verbo([increases]), complemento([in, 'beta-globin', gene, transcription, and, 'induction,', and, inhibited, 'long-term', 'beta-globin', gene, silencing])]). relacion([sujeto(['These', results, indicate, that, a, relatively, small, 'cis-acting', element, is, able, to]), verbo([enhance]), complemento([remodeling, of, promoter, chromatin, structure, resulting, in, increased, 'beta-globin', gene, expression])]). relacion([sujeto(['The', 'lineage-restricted', transcription, factor, 'GATA-1', is]), verbo([required]), complemento([for, differentiation, of, erythroid, and, megakaryocytic, cells])]). relacion([sujeto(['We']), verbo([have]), complemento([localized, a, 317, base, pair, 'cis-acting', regulatory, 'element,', 'HS', 'I,', associated, with, a, 'hematopoietic-specific', 'DNase', 'I', hypersensitive, 'site,', which, lies, approx])]). relacion([sujeto([63, '%', nucleotide, identity, with, a, more]), verbo([conserved]), complemento([core, of, 169, base, pairs, '(', 86, '%', 'identity)'])]). relacion([sujeto(['The', composite, motif]), verbo([binds]), complemento([a, 'multi-protein', 'hematopoietic-specific', transcription, factor, complex, which, includes, 'GATA-1,', 'SCL/tal-1,', 'E2A,', 'Lmo2', and, 'Ldb-1'])]). relacion([sujeto(['Strict', dependence, of, 'HS', 'I', activity, on, a, 'GATA', site, implies, that, assembly, of, a, protein, complex, containing, a, 'GATA-factor,', presumably, 'GATA-1', or, 'GATA-2,', is, critical, to]), verbo([activating]), complemento([or, maintaining, its, function])]). relacion([sujeto(['Further', dissection, of, the, 317, base, pair, region, demonstrates, 'that,', whereas, all, 317, base, pairs, are]), verbo([required]), complemento([for, expression, in, 'megakaryocytes,', only, the, 5, '\'', 62, base, pairs, are, needed, for, 'erythroid-specific', reporter, expression])]). relacion([sujeto(['Vertebrate', embryonic, hematopoiesis, is, a, complex, process, that]), verbo([involves]), complemento([a, number, of, cellular, 'interactions,', notably, those, occurring, between, endothelial, and, blood, cells])]). relacion([sujeto(['Cell', transplantation, studies]), verbo([have]), complemento([revealed, that, the, endocardial, defect, in, cloche, is, 'cell-autonomous:', 'wild-type', cells, can, form, endocardium, in, mutant, 'hosts,', but, mutant, cells, never, contribute, to, the, endocardium, in, 'wild-type', or, mutant, hosts])]). relacion([sujeto(['Alternatively,', cloche, could, be]), verbo([required]), complemento(['cell-autonomously', in, the, blood, cells, themselves])]). relacion([sujeto(['We']), verbo([found]), complemento([that, transplanted, 'wild-type', cells, were, much, more, likely, than, mutant, cells, to, contribute, to, circulating, blood, in, a, 'wild-type', host])]). relacion([sujeto(['These', data, indicate, that, cloche, is]), verbo([required]), complemento(['cell-autonomously', in, blood, cells, for, their, differentiation, 'and/or', proliferation])]). relacion([sujeto(['When', we, assessed, early, expression, of, the, erythropoietic, gene, 'gata-1', in, transplant, 'recipients,', we]), verbo([found]), complemento([that, mutant, blastomeres, were, as, likely, as, 'wild-type', blastomeres, to, give, rise, to, 'gata-1-expressing', cells, in, a, 'wild-type', host])]). relacion([sujeto(['Together,', these, two, sets, of, data, argue, that, cloche, is, not]), verbo([required]), complemento(['cell-autonomously', for, the, differentiation, of, red, blood, 'cells,', as, assayed, by, 'gata-1', 'expression,', but, rather, for, their, proliferation, 'and/or', 'survival,', as, assayed, by, their, contribution, to, circulating, blood])]). relacion([sujeto(['In', 'addition,', we]), verbo([found]), complemento([that, transplanted, 'wild-type', cells, were, less, likely, to, express, 'gata-1', in, a, mutant, environment, than, in, a, 'wild-type', 'one,', suggesting, that, cloche, also, acts, 'non-autonomously', in, red, blood, cell, differentiation])]). relacion([sujeto(['Thus,', cloche, appears, to, be]), verbo([required]), complemento([in, erythropoiesis, cell, 'non-autonomously', at, a, step, prior, to, 'gata-1', 'expression,', and, 'cell-autonomously', subsequently])]). relacion([sujeto(['Friend', of, 'GATA-1', '(', 'FOG-1)', is, a, zinc, finger, protein, that]), verbo([has]), complemento([been, shown, to, interact, physically, with, the, erythroid, 'DNA-binding', protein, 'GATA-1', and, modulate, its, transcriptional, activity])]). relacion([sujeto(['Recently,', two, new, members, of, the, 'FOG', family]), verbo([have]), complemento([been, 'identified:', a, mammalian, 'protein,', 'FOG-2,', that, also, associates, with, 'GATA-1', and, other, mammalian, 'GATA', 'factors;', and, 'U-shaped,', a, 'Drosophila', protein, that, interacts, with, the, 'Drosophila', 'GATA', protein, 'Pannier'])]). relacion([sujeto(['FOG', proteins, contain, multiple, zinc, fingers, and, it]), verbo([has]), complemento([been, shown, previously, that, the, sixth, finger, of, 'FOG-1', interacts, specifically, with, the, 'N-finger', but, not, the, 'C-finger', of, 'GATA-1'])]). relacion([sujeto(['Here', we, show, that, fingers, 1, ',', 5, and, 9, of, 'FOG-1', also]), verbo([interact]), complemento([with, the, 'N-finger', of, 'GATA-1', and, that, 'FOG-2', and, 'U-shaped', also, contain, multiple, 'GATA-interacting', fingers])]). relacion([sujeto(['We', define, the, key, contact, residues, and, show, that, these, residues, are, highly]), verbo([conserved]), complemento([in, 'GATA-interacting', fingers])]). relacion([sujeto(['We', examine, the, effect, of, selectively, mutating, the, four]), verbo([interacting]), complemento([fingers, of, 'FOG-1', and, show, that, each, contributes, to, 'FOG-1\'s', ability, to, modulate, 'GATA-1', activity])]). relacion([sujeto(['Finally,', we, show, that, 'FOG-1', can, repress, 'GATA-1-mediated', activation, and, present, evidence, that, this, ability]), verbo([involves]), complemento([the, recently, described, 'CtBP', 'co-repressor', proteins, that, recognize, all, known, 'FOG', proteins])]). relacion([sujeto(['The', replaced, enhancer, is, propagated, to, the, 5, '\'', 'LTR', upon, integration, into, the]), verbo([target]), complemento([cell, genome])]). relacion([sujeto(['Packaging', of, viral, 'particles,', integration, into, the]), verbo([target]), complemento(['genome,', and, stability, of, the, integrated, provirus, are, not, affected, by, the, 'LTR', modification])]). relacion([sujeto(['Enhancer', replacement, is, therefore, an, effective, strategy, to]), verbo([target]), complemento([expression, of, a, retroviral, transgene, to, a, specific, progeny, of, transduced, hematopoietic, stem, cells])]). relacion([sujeto(['In', the, absence, of, the, hematopoietic, transcription, factor, 'GATA-1,', mice, develop, thrombocytopenia, and, an]), verbo([increased]), complemento([number, of, megakaryocytes, characterized, by, marked, ultrastructural, abnormalities])]). relacion([sujeto(['To', begin, to, address, 'this,', we]), verbo([have]), complemento([performed, a, more, detailed, examination, of, the, megakaryocytes, and, platelets, produced, in, mice, that, lack, 'GATA-1', in, this, lineage])]). relacion([sujeto(['Our', analysis, demonstrates, that, compared, with, their, normal, 'counterparts,', 'GATA-1-deficient', primary, megakaryocytes, exhibit, significant, hyperproliferation, in, liquid, 'culture,']), verbo([suggesting]), complemento([that, the, megakaryocytosis, seen, in, animals, is, nonreactive])]). relacion([sujeto(['Morphologically,', these, mutant, megakaryocytes, are, small, and, show, evidence, of, retarded]), verbo([nuclear]), complemento([and, cytoplasmic, development])]). relacion([sujeto(['A', significant, proportion, of, these, cells, do, not, undergo, endomitosis, and]), verbo([express]), complemento([markedly, lower, levels, of, mRNA, of, all, 'megakaryocyte-associated', genes, 'tested,', including, 'GPIbalpha,', 'GPIbbeta,', platelet, factor, 4, '(', 'PF4),', 'c-mpl,', and, p45, 'NF-E2'])]). relacion([sujeto(['However,', a, number, of, recent]), verbo([reports]), complemento([have, implicated, particular, 'ZnFs', in, the, mediation, of, 'protein-protein', interactions])]). relacion([sujeto(['The', 'N-terminal', 'ZnF', of, 'GATA-1', '(', 'NF)', is, one, such, 'finger,', having, been, shown, to]), verbo([interact]), complemento([with, a, number, of, other, 'proteins,', including, the, recently, discovered, transcriptional, 'co-factor', 'FOG'])]). relacion([sujeto(['Comparisons', of, the, 'NF', structure, with, those, of, other, 'C4-type', zinc]), verbo([binding]), complemento(['motifs,', including, hormone, receptor, and, 'LIM', 'domains,', also, reveal, substantial, structural, homology])]). relacion([sujeto(['FOG,', a, zinc, finger, 'protein,']), verbo([interacts]), complemento([with, the, amino, '(', 'N)', finger, of, 'GATA-1', and, cooperates, with, 'GATA-1', to, promote, differentiation])]). relacion([sujeto(['To', determine, whether, this, interaction, is, critical, for, 'GATA-1', 'action,', we, selected, 'GATA-1', mutants, in, yeast, that, fail, to]), verbo([interact]), complemento([with, 'FOG', but, retain, normal, 'DNA', 'binding,', as, well, a, compensatory, 'FOG', mutant, that, restores, interaction])]). relacion([sujeto(['These', novel, 'GATA-1', mutants, do, not]), verbo([promote]), complemento([erythroid, differentiation, of, 'GATA-1-', erythroid, cells])]). relacion([sujeto(['These', findings]), verbo([provide]), complemento([a, paradigm, for, dissecting, 'protein-protein', associations, involved, in, mammalian, development])]). relacion([sujeto(['We']), verbo([have]), complemento([investigated, by, electrophoretic, mobility, shift, assay, '(', 'EMSA)', the, level, of, 'GATA-1', 'DNA-binding', activity, in, nuclear, extracts, prepared, from, the, human, erythroleukaemic, cell, 'line,', 'K562,', after, erythroid, induction, by, 'hemin,', sodium, butyrate, '(', 'NaB)', or, 'Trichostatin', 'A', or, treatment, with, 'N', -, acetylcysteine, '(', 'NAC)'])]). relacion([sujeto(['Relative', to, extract, from, untreated, 'cells,', 'GATA-1']), verbo([binding]), complemento([activity, increased, markedly, in, all, cases])]). relacion([sujeto(['Incubation', of]), verbo([induced]), complemento([but, not, uninduced, 'K562', extracts, with, phosphatase, prior, to, 'EMSA', weakened, the, binding, 'activity,', suggesting, that, the, increase, in, 'GATA-1', binding, following, induction, of, 'K562', cells, was, a, consequence, of, phosphorylation])]). relacion([sujeto(['When', the, mouse, erythroleukaemic, cell, line, 'MEL', was]), verbo([induced]), complemento([with, dimethylsulphoxide, '(', 'DMSO),', 'NaB', or, 'NAC,', 'GATA-1', binding, activity, fell, with, 'DMSO,', rose, significantly, with, 'NaB', and, remained, at, about, the, same, level, in, 'NAC-induced', cells])]). relacion([sujeto(['The', 'DNA-binding', activities, of]), verbo([induced]), complemento([and, uninduced, 'MEL', cell, nuclear, extracts, were, decreased, by, incubation, with, 'phosphatase,', showing, that, 'phosphoryl-ation', and, 'DNA', binding, of, 'GATA-1', are, already, optimalin, these, cells])]). relacion([sujeto(['Furthermore,', when, a, comparison, was, made, by, 'EMSA', of]), verbo([nuclear]), complemento([extracts, prepared, from, 'K562', and, 'MEL', cells, untreated, or, incubated, with, okadaic, 'acid,', a, phosphatase, 'inhibitor,', 'GATA-1', binding, was, seen, to, increase, with, 'K562', 'cells,', whereas, with, 'MEL', cells, there, was, no, change, in, 'GATA-1', binding])]). relacion([sujeto(['Overall', the, results]), verbo([suggest]), complemento([that, the, level, of, 'GATA-1', phosphorylation, increases, after, the, induction, of, 'K562,', but, not, 'MEL', 'cells,', where, 'GATA-1', is, already, highly, phosphorylated])]). relacion([sujeto(['Furthermore,', phosphorylation]), verbo([increases]), complemento([the, binding, affinity, of, 'GATA-1', for, a, canonical, binding, site])]). relacion([sujeto(['Butyric', acid, '(', 'BA)', is, known, to]), verbo([induce]), complemento([overexpression, of, fetal, hemoglobin, and, then, erythroid, differentiation])]). relacion([sujeto(['Nevertheless,', the, molecular, mechanisms]), verbo([involved]), complemento([in, 'BA-induced', differentiation, remain, largely, unknown])]). relacion([sujeto(['Previous']), verbo([reports]), complemento([have, shown, that, 'BA-induced', overexpression, of, erythroid, genes, occurred, at, the, transcriptional, 'level,', suggesting, the, involvement, of, erythroid, transcription, factors])]). relacion([sujeto(['Time-course', experiments, showed, that]), verbo([nuclear]), complemento([levels, of, 'GATA-1', and, p45, 'NF-E2', proteins, increased, during, 'BA', treatment])]). relacion([sujeto(['Moreover,', antisense, oligodeoxynucleotides]), verbo([targeting]), complemento([either, 'GATA-1', or, p45, 'NF-E2', proteins, inhibited, both, protein, expression, and, 'BA-induced', differentiation])]). relacion([sujeto(['These', results]), verbo([provide]), complemento([the, first, direct, evidence, for, the, requirement, of, 'GATA-1', and, 'NF-E2', in, 'BA-induced', differentiation, process])]). relacion([sujeto(['GATA-1', is, a, transcription, factor]), verbo([required]), complemento([for, development, of, erythroid, cells])]). relacion([sujeto(['We']), verbo([report]), complemento([here, the, identification, of, distinct, 'cis-acting', elements, that, cooperate, to, confer, on, 'GATA-1', its, hematopoietic, expression, pattern])]). relacion([sujeto(['A', distal, double, 'GATA', element, is]), verbo([required]), complemento([for, maintaining, and, enhancing, the, hematopoietic, expression, of, 'GATA-1'])]). relacion([sujeto(['The', 'erythroid-specific', activity, of, the, 'GATA-1', promoter, is, also]), verbo([enhanced]), complemento([by, a, 49, -, bp, sequence, element, located, 218, bp, upstream, of, the, 'CACCC', element, and, a, 'CCAAT', box, adjacent, to, the, double, 'GATA', motif])]). relacion([sujeto(['Finally,', the, hematopoietic, specificity, of, the, 'GATA-1', promoter, is, secured, by, a, negative, 'cis-acting', element, that]), verbo([inhibits]), complemento([expression, in, the, notochord])]). relacion([sujeto(['In', the, rat, platelet, factor, 4, '(', 'PF4)', 'promoter,', 'Ets', motifs, and, 'GATA', motifs, are, located, at, positions, -, 880, ',', -, 75, and, -, 135, ',', -, 30, ',', 'respectively,', and, their, motifs, are]), verbo([found]), complemento([in, the, promoter, region, of, most, megakaryocyte, protein, genes])]). relacion([sujeto(['A', single, disruption, of, either, -, '75Ets,', -, 135, 'GATA,', or, -, 30, 'GATA', significantly, reduced, 'PF4', promoter, 'activity,', and, double, disruptions]), verbo([involving]), complemento([these, motifs, completely, abolished, it])]). relacion([sujeto(['Furthermore,', 'gel-retardation', assays, revealed, that, 'Ets-1', and, 'GATA-1', proteins, from, 'HEL', and, 'MEG-01', cells]), verbo([bound]), complemento([to, the, 'Ets', motifs, and, 'GATA', 'motifs,', respectively])]). relacion([sujeto(['Co-transfection', experiments, showed, that, the, overexpression, of, 'Ets-1', 'and/or', 'GATA-1']), verbo([enhanced]), complemento([the, expression, of, the, 'PF4', promoter, reporter, gene])]). relacion([sujeto(['When', 'HEL', cells, were, treated, with, dimethylsulfoxide, in, order, to]), verbo([induce]), complemento([differentiation, into, 'megakaryocytes,', the, mRNA, level, of, 'ets-1', increased, 10, -, 'fold,', which, might, be, directly, correlated, with, the, significant, increase, in, 'PF4', mRNA, level, induced, by, dimethylsulfoxide])]). relacion([sujeto(['All', these, results, strongly]), verbo([suggest]), complemento([that, both, 'Ets-1', and, 'GATA-1', play, key, roles, in, the, positive, regulation, of, 'PF4', gene, expression])]). relacion([sujeto(['A', unique, 'A/T-rich', sequence, '(', 5, '\'', -, 'AAAAAGTAAAAA-GTAAAAAAGTAAAAAG-3),', referred, to, as, the, 'AGTA', 'repeat,', is]), verbo([found]), complemento([in, the, silencer, region, of, the, pumpkin, ascorbate, oxidase, gene])]). relacion([sujeto(['A', cDNA, for, protein, '(', 'AOBP)', that]), verbo([binds]), complemento([to, the, 'AGTA', repeat, was, isolated, from, pumpkin, by, the, southwestern, method])]). relacion([sujeto(['The', 'AOBP', protein]), verbo([has]), complemento([a, new, class, of, 'zinc/DNA-binding', domain, named, 'Dof/MOA', domain, that, is, highly, conserved, in, many, plant, proteins, and, is, significantly, related, to, those, of, steroid, hormone, receptors, and, 'GATA1'])]). relacion([sujeto(['Gel', retardation, analysis, indicated, that, 'AOBP']), verbo([bound]), complemento([to, the, 'AGTA', repeat, through, the, 'Dof/MOA', domain])]). relacion([sujeto(['Metal', 'chelators,', 1, ',', 10, -, phenanthroline, and, 'EDTA,', specifically]), verbo([inhibited]), complemento([the, 'DNA', binding, of, 'AOBP,', indicating, that, metal, coordination, plays, an, important, role, in, 'DNA', binding, of, 'AOBP'])]). relacion([sujeto(['Thus,', the, 'Dof/MOA', domain]), verbo([acts]), complemento([as, a, 'zinc/DNA-binding', domain, in, 'AOBP'])]). relacion([sujeto(['Gel', retardation, analysis, with, mutated, oligonucleotides]), verbo([suggested]), complemento([that, the, 'Dof/MOA', domain, recognized, the, 'AGTA', core, sequence])]). relacion([sujeto(['AOBP', mRNA, was]), verbo([expressed]), complemento([in, mature, tissues, of, 'pumpkin,', but, was, expressed, only, in, small, amounts, or, was, not, expressed, in, growing, tissues])]). relacion([sujeto(['Modification', of, 'histones,', 'DNA-binding', proteins]), verbo([found]), complemento([in, 'chromatin,', by, addition, of, acetyl, groups, occurs, to, a, greater, degree, when, the, histones, are, associated, with, transcriptionally, active, 'DNA'])]). relacion([sujeto(['A', breakthrough, in, understanding, how, this, acetylation, is]), verbo([mediated]), complemento([was, the, discovery, that, various, transcriptional, 'co-activator', proteins, have, intrinsic, histone, acetyltransferase, activity, '(', for, 'example,', 'Gcn5p,', 'PCAF,', 'TAF(II)250', and, 'p300/CBP'])]). relacion([sujeto(['It', is]), verbo([associated]), complemento([in, vivo, with, the, acetyltransferase, 'p300/CBP'])]). relacion([sujeto(['Here', we]), verbo([report]), complemento([that, 'GATA-1', is, acetylated, in, vitro, by, p300])]). relacion([sujeto(['This', significantly]), verbo([increases]), complemento([the, amount, of, 'GATA-1', bound, to, 'DNA', and, alters, the, mobility, of, 'GATA-1-DNA', 'complexes,', suggestive, of, a, conformational, change, in, 'GATA-1'])]). relacion([sujeto(['GATA-1', is, also, acetylated, in, vivo, and, acetylation, directly]), verbo([stimulates]), complemento(['GATA-1-dependent', transcription])]). relacion([sujeto(['These', processes, are, controlled, in, large, part, by, 'cell-restricted', transcription, factors, which, cooperate, with, more, widely]), verbo([expressed]), complemento([factors, to, direct, 'lineage-specific', gene, expression])]). relacion([sujeto(['Candidate', hematopoietic, transcriptional, regulators]), verbo([have]), complemento([been, identified, by, characterizing, factors, mediating, 'cell-specific', gene, transcription, and, by, defining, genes, involved, in, chromosomal, rearrangements, in, leukemia])]). relacion([sujeto(['The', application, of, transgenic, and, embryonic, stem, cell, methods]), verbo([have]), complemento([provided, insights, into, their, in, vivo, functions, and, suggested, mechanisms, by, which, lineage, selection, may, be, achieved])]). relacion([sujeto(['Herein', studies, of, 'GATA-1', are, reviewed, to, illustrate, how, manipulations, of, its, locus, in, the, mouse]), verbo([have]), complemento([contributed, to, current, understanding, in, unique, and, unexpected, ways])]). relacion([sujeto(['In', 'particular,', zinc, 'fingers,', usually, regarded, as, 'DNA-binding', 'domains,', are, now, also, known, to, be]), verbo([involved]), complemento([in, mediating, contacts, between, proteins])]). relacion([sujeto(['We']), verbo([have]), complemento([investigated, the, interaction, between, the, erythroid, transcription, factor, 'GATA-1', and, its, 'partner,', the, 9, zinc, finger, 'protein,', 'FOG', '(', 'Friend', 'Of', 'GATA)'])]). relacion([sujeto(['Using', a, scanning, substitution, strategy, we, identify, key, residues, within, the, 'GATA-1', 'N-finger', which, are]), verbo([required]), complemento([for, 'FOG', binding])]). relacion([sujeto(['These', residues, are]), verbo([conserved]), complemento([in, the, 'N-fingers', of, all, 'GATA', proteins, known, to, bind, 'FOG,', but, are, not, found, in, the, respective, 'C-fingers'])]). relacion([sujeto(['Although', the, importance, of, 'GATA-1', in, both, primitive, and, definitive, hematopoietic, lineages]), verbo([has]), complemento([been, shown, in, 'vivo,', the, precise, roles, played, by, 'GATA-1', during, definitive, hematopoiesis, have, not, yet, been, clarified])]). relacion([sujeto(['In', vitro, differentiation, of, embryonic, stem, '(', 'ES)', cells, using, 'OP9', stroma, cells, can, generate, primitive, and, definitive, hematopoietic, cells, 'separately,', and, we]), verbo([have]), complemento([introduced, a, method, that, separates, hematopoietic, progenitors, and, differentiated, cells, produced, in, this, system])]). relacion([sujeto(['Closer', examination, showed, that, the, expression, of, erythroid, transcription, factors, in, this, system, is]), verbo([regulated]), complemento([in, a, differentiation, 'stage-specific', manner])]). relacion([sujeto([5, mutant, 'ES', cells, along, both, primitive, and, definitive, lineages, was]), verbo([arrested]), complemento([in, this, 'ES', cell, culture, system])]). relacion([sujeto(['Although', the, 'maturation-arrested', primitive, lineage, cells, did, not]), verbo([express]), complemento([detectable, amounts, of, 'epsilony-globin', 'mRNA,', the, blastlike, cells, accumulated, in, the, definitive, stage, showed, 'beta-globin', mRNA, expression, at, approximately, 70, '%', of, the, wild, type])]). relacion([sujeto(['Importantly,', the, 'TER119', antigen, was]), verbo([expressed]), complemento([and, porphyrin, was, accumulated, in, the, definitive, 'cells,', although, the, levels, of, both, were, reduced, to, approximately, 10, '%', ',', indicating, that, maturation, of, definitive, erythroid, cells, is, arrested, by, the, lack, of, 'GATA-1', with, different, timing, from, that, of, the, primitive, erythroid, cells])]). relacion([sujeto(['We', also]), verbo([found]), complemento([that, the, hematopoietic, progenitor, fraction, of, 'GATA-1'])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, the, 'GATA-1'])]). relacion([sujeto(['Previously', we]), verbo([have]), complemento([shown, that, overexpression, of, 'PU'])]). relacion([sujeto(['In', this, 'study,', we, examined, the, dynamics, of, 'GATA-1', and, 'NF-E2', hematopoietic, transcription, factors, during, the, induction, of, 'apoptosis,', because, 'GATA-1']), verbo([has]), complemento([been, shown, to, be, implicated, in, survival, of, erythroid, cells])]). relacion([sujeto(['Complex', formation, in]), verbo([nuclear]), complemento([extracts, of, parental, 'MEL', cells, was, reduced, when, they, were, mixed, with, those, of, apoptotic, 'cells,', suggesting, that, apoptotic, cells, may, contain, a, 'factor(s)', preventing, 'GATA-1', from, binding, to, 'DNA'])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, reduction, of, the, 'DNA-binding', activity, of, 'GATA-1', may, partly, account, for, 'PU'])]). relacion([sujeto([1, -]), verbo([mediated]), complemento([apoptosis, in, 'MEL', cells])]). relacion([sujeto(['We']), verbo([have]), complemento([isolated, and, characterized, a, human, glutathione, transferase, 'A4', '(', 'hGSTA4)', subunit, gene, from, a, yeast, artificial, chromosome, containing, several, other, glutathione, transferase, alpha, genes, and, pseudogenes])]). relacion([sujeto(['The', homodimeric, protein, 'hGSTA4-4,', is]), verbo([involved]), complemento([in, the, detoxification, of, 4, -, hydroxynonenal, and, other, reactive, electrophiles, produced, by, oxidative, 'metabolism,', and, may, have, a, significant, role, in, protecting, intracellular, components, from, oxidative, damage])]). relacion([sujeto(['The', hGSTA4, gene, spans, nearly, 18, 'kb,', contains, seven, 'exons,', maps, onto, chromosome, 6, 'p12,', and, lies, in, close, proximity, to, the, 7, 'SK', small]), verbo([nuclear]), complemento(['RNA', gene, in, a, 'head-to-tail', orientation])]). relacion([sujeto(['The', transcription, initiation, site]), verbo([has]), complemento([been, determined, by, primer, extension, analysis, and, is, located, 135, bp, upstream, of, intron, 1])]). relacion([sujeto(['Isolation', and, sequencing, of, the, hGSTA4, gene, 5, '\'', -, flanking, region, revealed, it, to, be, devoid, of, 'TATA', or, 'CCAAT', boxes, but, it, does, contain, an, initiator, element, overlapping, the, transcription, start, 'site,', a, 'GC', box, and, putative]), verbo([binding]), complemento([sites, for, transcription, factors, 'AP1,', 'STAT,', 'GATA1', and, 'NF-kappaB'])]). relacion([sujeto(['Reverse', 'transcription-PCR', analysis, revealed, that, hGSTA4, mRNA, was, present, in, all, the, tissues, 'tested,', although, in, low, 'amounts,']), verbo([suggesting]), complemento([that, this, subunit, may, be, ubiquitously, expressed])]). relacion([sujeto(['GATA-1', may, be]), verbo([involved]), complemento([in, the, expression, of, an, erythroid, phenotype, in, acute, leukemia])]). relacion([sujeto(['We', generated, 'HL-60', transfectants, exogenously]), verbo([expressing]), complemento(['GATA-1'])]). relacion([sujeto(['The', majority, of, 'HL-60', cells]), verbo([expressing]), complemento(['GATA-1', lacked, azurophilic, 'granules,', and, electron, microscopic, analysis, revealed, that, myeloperoxidase, activity, was, negative])]). relacion([sujeto(['These', findings]), verbo([suggest]), complemento([that, besides, 'GATA-1,', a, third, factor, may, be, required, for, the, expression, of, mature, erythroid, phenotypes])]). relacion([sujeto(['In', 'addition,', our, results, indicate, that, 'GATA-1', is]), verbo([involved]), complemento([in, inactivation, of, myeloperoxidase, and, activation, of, the, platelet, peroxidase])]). relacion([sujeto(['Zinc', fingers, are]), verbo([recognized]), complemento([as, small, protein, domains, that, bind, to, specific, 'DNA', sequences])]). relacion([sujeto(['Recently', 'however,', zinc, fingers, from, a, number, of, 'proteins,', in, particular, the, 'GATA', family, of, transcription, 'factors,']), verbo([have]), complemento([also, been, implicated, in, specific, 'protein-protein', interactions])]). relacion([sujeto(['The', erythroid, protein, 'GATA-1', contains, two, zinc, 'fingers:', the, 'C-finger,', which, is, sufficient, for, 'sequence-specific', 'DNA-binding,', and, the, 'N-finger,', which, appears, both, to]), verbo([modulate]), complemento(['DNA-binding', and, to, interact, with, other, transcription, factors])]). relacion([sujeto(['We']), verbo([have]), complemento([expressed, and, purified, the, 'N-finger', domain, and, investigated, its, involvement, in, the, 'self-association', of, 'GATA-1'])]). relacion([sujeto(['We', demonstrate, that, this, domain, does, not, homodimerize, but, instead, makes, intermolecular, contacts, with, the, 'C-finger,']), verbo([suggesting]), complemento([that, 'GATA', dimers, are, maintained, by, reciprocal, 'N-finger-C-finger', contacts])]). relacion([sujeto(['Moreover,', mutations, that, impair, 'GATA-1', 'self-association', also, interfere, with, its, ability, to]), verbo([activate]), complemento([transcription, in, transfection, studies])]). relacion([sujeto(['Despite', the, major, functions, of, the, basic, 'helix-loop-helix', transcription, factor, 'TAL-1', in, hematopoiesis, and, 'T-cell', 'leukemogenesis,', no, 'TAL-1']), verbo([target]), complemento([gene, has, been, identified])]). relacion([sujeto(['Using', immunoprecipitation, of, genomic, fragments]), verbo([bound]), complemento([to, 'TAL-1', in, the, chromatin, of, murine, 'erythro-leukemia', '(', 'MEL)', 'cells,', we, found, that, 10, '%', of, the, immunoselected, fragments, contained, a, 'CAGATG', or, a, 'CAGGTG', 'E-box,', followed, by, a, 'GATA', site])]). relacion([sujeto(['We', studied, one, of, these, fragments, containing, two, 'E-boxes,', 'CAGATG', and, 'CAGGTC,', followed, by, a, 'GATA', 'motif,', and, showed, that, 'TAL-1']), verbo([binds]), complemento([to, the, 'CAGGTG', 'E-box', with, an, affinity, modulated, by, the, 'CAGATG', or, the, 'GATA', 'site,', and, that, the, 'CAGGTG-GATA', motif, exhibits, positive, transcriptional, activity, in, 'MEL', but, not, in, 'HeLa', cells])]). relacion([sujeto(['This', immunoselected, sequence, is, located, within, an, intron, of, a, new, gene, 'co-expressed', with, 'TAL-1', in, endothelial, and, erythroid, 'cells,', but, not]), verbo([expressed]), complemento([in, fibroblasts, or, adult, liver, where, no, 'TAL-1', mRNA, was, detected])]). relacion([sujeto(['Finally,', in, vitro, differentiation, of, embryonic, stem, cells, towards, the, 'erythro/megakaryocytic', pathways, showed, that, the, 'TAL-1']), verbo([target]), complemento([gene, expression, followed, 'TAL-1', and, 'GATA-1', expression])]). relacion([sujeto(['These', results, establish, that, 'TAL-1', is, likely, to]), verbo([activate]), complemento([its, target, genes, through, a, complex, that, binds, an, 'E-box-GATA', motif, and, define, the, first, gene, regulated, by, 'TAL-1'])]). relacion([sujeto(['Mechanisms', of, platelet, production, and]), verbo([release]), complemento([by, mammalian, megakaryocytes, are, poorly, understood])]). relacion([sujeto(['Proplatelets', are, filamentous, extensions, of, terminally, differentiated, megakaryocytes, that, are, thought, to, represent, one, mechanism, of, platelet, 'release;', 'however,', these, structures]), verbo([have]), complemento([largely, been, recognized, in, cultured, cells, and, there, has, been, no, correlation, between, thrombocytopoiesis, in, vivo, and, proplatelet, formation])]). relacion([sujeto(['Mice', lacking, transcription, factor, 'NF-E2']), verbo([have]), complemento([a, late, arrest, in, megakaryocyte, 'maturation,', resulting, in, profound, thrombocytopenia])]). relacion([sujeto(['Similarly,', megakaryocytes, from, thrombocytopenic, mice, with, 'lineage-selective']), verbo([loss]), complemento([of, transcription, factor, 'GATA-1', produce, proplatelets, very, rarely])]). relacion([sujeto(['These', findings, establish, a, significant, correlation, between, thrombocytopoiesis, and, proplatelet, formation, and]), verbo([suggest]), complemento([that, the, latter, represents, a, physiologic, mechanism, of, platelet, release])]). relacion([sujeto(['pombe)', 'GATA', 'factors,', we]), verbo([have]), complemento([isolated, the, 'gaf1+', gene, '(', 'GATA-factor', like, 'gene)', in, 'S'])]). relacion([sujeto(['The', predicted, amino, acid, '(', 'aa)', sequence, of, 'Gaf1']), verbo([reveals]), complemento([a, single, zinc, finger, domain, typical, of, fungal, 'GATA', 'factors,', and, the, zinc, finger, exhibits, 60, '%', aa, identity, to, that, of, human, 'GATA-1'])]). relacion([sujeto(['Disruption', of, this, gene]), verbo([has]), complemento([no, effect, on, cell, viability, and, growth, rate])]). relacion([sujeto(['The', 'GST-Gaf1', fusion, protein]), verbo([binds]), complemento([specifically, to, 'GATA', motifs, of, its, own, promoter, as, well, as, 'DAL7', 'UAS,', a, canonical, 'GATA', motif, of, 'Saccharomyces', cerevisiae, '(', 'S'])]). relacion([sujeto(['cerevisiae)', 'The', specific, 'DNA-binding', activity, resides, within, the, 'N-terminal', half, of, 'Gaf1', '(', 'Gaf1N;', aa, 1, -, 120, ')', containing, the, zinc, 'finger,', whereas, the, 'C-terminal', half, '(', 'Gaf1C;', aa, 121, -, 290, ')', contains, transactivation, sequences, that]), verbo([induce]), complemento([the, expression, of, the, lacZ, reporter, when, fused, to, the, 'GAL4', 'DNA', binding, domain])]). relacion([sujeto(['Transcriptional', initiation, in, fibroblasts, is]), verbo([regulated]), complemento([by, 'c-Fos', and, gives, rise, to, a, rare, 5, -, kb, mRNA, and, an, abundant, 2.7, -, kb, mRNA])]). relacion([sujeto(['These', transcripts, are]), verbo([translated]), complemento([into, a, 'receptor-like', 'membrane-anchored', protein, and, a, secreted, protein, consisting, only, of, the, ectodomain])]). relacion([sujeto(['c-Fos', and, a, 'T1', 'enhancer,', which]), verbo([have]), complemento([previously, been, identified, to, be, essential, for, 'T1', expression, in, 'fibroblasts,', were, not, required, for, calcium, 'ionophore-mediated', 'T1', gene, upregulation])]). relacion([sujeto(['Overexpression', of, the, transcription, factor, 'GATA-1', in, mast, cells]), verbo([caused]), complemento([elevated, 'T1', synthesis])]). relacion([sujeto(['Mutational', analysis, revealed, that, all, three, 'GATA', elements, are]), verbo([involved]), complemento([in, 'T1', gene, expression])]). relacion([sujeto(['Point', mutations, within, the, middle, 'GATA', element, eliminated, promoter, activity, 'completely,', while, mutations, of, the, distal, and, proximal, 'GATA']), verbo([binding]), complemento([sites, reduced, promoter, strength, by, factors, of, 2, and, 5, ',', respectively])]). relacion([sujeto(['Exogenous', expression, of, 'GATA-1', was, not, sufficient, to]), verbo([activate]), complemento([the, mast, 'cell-specific', promoter, in, 'NIH', 3, 'T3', fibroblasts])]). relacion([sujeto(['With', the, screening, of, a, human, genomic, library, and, the, combination, of]), verbo([primer]), complemento([walking, and, 'PCR', 'sequencing,', we, found, that, the, entire, 'TR2', orphan, receptor, gene, coding, region, and, 5, '\'', -, untranslated, region, feature, 13, introns, and, 14, 'exons,', and, that, the, consensus, splice, sequences, '(', 'GT-AG)', are, present, in, all, 'intron-exon', boundaries])]). relacion([sujeto(['Within', the, region, that, codes, for, the, 'DNA']), verbo([binding]), complemento(['domain,', 'TR2', orphan, receptor, gene, has, a, distinct, 'intron-exon', junction])]). relacion([sujeto(['Whereas', all, other, known, steroid, receptors]), verbo([have]), complemento([one, splice, site, that, separates, their, first, and, second, zinc, fingers, in, the, 'DNA', binding, 'domain,', 'TR2', orphan, receptor, has, a, rare, splice, site, located, in, the, middle, of, its, first, zinc, finger])]). relacion([sujeto(['Sequence', analysis, of, a, 2.7, -, kb, 'DNA', fragment, upstream, of, the, 'TR2', orphan, receptor, translation, start, codon, unveiled, several, potential, 'cis-acting', 'elements,', such, as, 'AP-1,', 'HNF-5,', 'GATA1']), verbo([binding]), complemento(['sites,', and, 'GC', boxes])]). relacion([sujeto(['Using', fluorescence, in, situ, hybridization, combined, with, a, 'high-resolution', 'G-banding', 'technique,', we]), verbo([found]), complemento([that, the, 'TR2', orphan, receptor, gene, was, mapped, to, human, chromosome, 12, at, band, 'q22,', whereas, the, structurally, closely, related, 'TR4', orphan, receptor, gene, was, mapped, to, human, chromosome, 3, at, band, q24])]). relacion([sujeto(['The', 'TAL1', gene, is, disrupted, by, translocation, or, deletion, '(', 'tal(d))', in, up, to, 30, '%', of, 'T-cell', acute, lymphoblastic, leukaemia, '(', 'T-ALL),']), verbo([leading]), complemento([to, aberrant, transcriptional, 'activation,', as, a, 'SIL-TAL1', fused, transcript, in, 'tal(d)'])]). relacion([sujeto(['It']), verbo([has]), complemento([been, suggested, that, 'TAL1', transcription, occurs, in, approximately, 50, '%', of, a, 'T-ALLs', without, apparent, rearrangement])]). relacion([sujeto(['To', investigate, the, cellular, origin, of, 'TAL1', we, exploited, the, fact, that, 'GATA1', and, 'TAL1', are, 'co-ordinately']), verbo([expressed]), complemento([in, 'non-lymphoid', haemopoietic, 'cells,', whereas, only, the, latter, is, found, in, 'T-ALL'])]). relacion([sujeto(['GATA1', was, detected, in, 10, /, 23, '(', 43, '%', ')', 'TAL1-negative', 'T-ALLs', but, in, 17, /, 19, '(', 89, '%', ')', '\'', 'unexplained\'', 'TAL1-positive', 'cases,']), verbo([suggesting]), complemento([a, common, 'non-lymphoid', cellular, origin])]). relacion([sujeto(['Immunocytochemical', analysis, with, a, 'TAL1-specific', monoclonal, antibody, showed]), verbo([nuclear]), complemento([expression, in, the, blasts, of, 10, /, 34, '(', 29, '%', ')', 'cases,', including, 8, /, 10, 'SIL-TAL1+', and, two, 'RT-PCR', 'TAL1+,', 'SIL-TAL1-', cases])]). relacion([sujeto(['We', therefore]), verbo([suggest]), complemento([that, appropriate, diagnostic, evaluation, of, 'T-ALL', should, include, molecular, detection, of, 'SIL-TAL1', transcripts, and, in, situ, immunocytochemical, detection, of, 'TAL1', protein, expression, by, leukaemic, blasts])]). relacion([sujeto(['Little', is, known, about, the, transcription, factors, that]), verbo([mediate]), complemento([lineage, commitment, of, multipotent, hematopoietic, precursors])]). relacion([sujeto([1, ',', which, is]), verbo([expressed]), complemento([in, myeloid, and, 'B', cells, and, is, required, for, the, development, of, both, these, lineages])]). relacion([sujeto(['This']), verbo([involves]), complemento([not, only, the, 'up-regulation', of, 'myeloid-specific', cell, surface, antigens, and, the, acquisition, of, myeloid, 'growth-factor', dependence, but, also, the, 'down-regulation', of, 'progenitor/thrombocyte-specific', 'cell-surface', markers, and, 'GATA-1'])]). relacion([sujeto(['Both', effects]), verbo([require]), complemento([an, intact, 'PU'])]). relacion([sujeto(['Whereas', sustained, activation, of, an, inducible, form, of, the, factor]), verbo([leads]), complemento([to, myeloid, lineage, 'commitment,', 'short-term', activation, leads, to, the, formation, of, immature, 'eosinophils,', indicating, the, existence, of, a, bilineage, intermediate])]). relacion([sujeto(['Our', results]), verbo([suggest]), complemento([that, 'PU'])]). relacion([sujeto([1]), verbo([induces]), complemento([myeloid, lineage, commitment, by, the, suppression, of, a, master, regulator, of, nonmyeloid, genes, '(', such, as, 'GATA-1)', and, the, concomitant, activation, of, multiple, myeloid, genes])]). relacion([sujeto(['AOBP,', a, 'DNA-binding', protein, in, 'pumpkin,', contains, a, 'Dof', domain, that, is, composed, of, 52, amino, acid, residues, and, is, highly]), verbo([conserved]), complemento([in, several, 'DNA-binding', proteins, of, higher, plants])]). relacion([sujeto(['The', 'Dof', domain]), verbo([has]), complemento([a, significant, resemblance, to, 'Cys2/Cys2', zinc, finger, 'DNA-binding', domains, of, steroid, hormone, receptors, and, 'GATA1,', but, has, a, longer, putative, loop, where, an, extra, 'Cys', residue, is, conserved])]). relacion([sujeto(['We', show, that, the, 'Dof', domain, in, 'AOBP', functions, as, a, zinc, finger, 'DNA-binding', domain, and]), verbo([suggest]), complemento([that, the, 'Cys', residue, uniquely, conserved, in, the, putative, loop, might, negatively, regulate, the, binding, to, 'DNA'])]). relacion([sujeto(['The', 'GATA-1', gene, encodes, a, transcription, factor]), verbo([expressed]), complemento([in, early, multipotent, haemopoietic, 'progenitors,', in, more, mature, cells, of, the, 'erythroid,', megakaryocytic, and, other, 'lineages,', but, not, in, late, myeloid, 'precursors;', its, function, is, essential, for, the, normal, development, of, the, erythroid, and, megakaryocytic, system])]). relacion([sujeto(['The', site, 1, enhancer, activity, depends, both, on, a, 'GATA-binding', site, '(', also, footprinted, in, 'vivo)', and, on, several, sites, capable, of]), verbo([binding]), complemento([relatively, ubiquitous, factors])]). relacion([sujeto(['Sites', 4, and, 5, ',', located, in, the, first, large, 'intron,']), verbo([have]), complemento([no, enhancer, 'activity;', they, include, a, long, array, of, potential, 'Ets-binding', sites])]). relacion([sujeto(['Although', these, sites, are, present, in, all, 'GATA-1-expressing', cells, 'studied,', they, are, the, only, strong, sites, detectable, in, 'FDCP-mix', multipotent, progenitor, 'cells,', most, of, which, do, not, yet]), verbo([express]), complemento(['GATA-1'])]). relacion([sujeto(['The', data, indicate, that, appropriate, 'GATA-1', regulation, may]), verbo([require]), complemento([the, 'co-operation', of, different, regulatory, elements, acting, at, different, stages, of, development, and, cell, differentiation])]). relacion([sujeto(['AC)', carrying, an]), verbo([activated]), complemento(['v-Ha-ras', oncogene, fused, to, the, embryonic, 'zeta-globin', promoter, develops, an, array, of, spontaneous, epithelial, and, mesenchymal, neoplasms])]). relacion([sujeto(['In', this]), verbo([report]), complemento([we, describe, the, 'morphological,', 'immunophenotypic,', and, molecular, features, of, a, unique, hematopoietic, neoplasm, in, these, mice])]). relacion([sujeto(['In', the, peripheral, 'blood,', there, is, a, marked]), verbo([increase]), complemento([in, the, number, of, metarubricytes, and, other, less, differentiated, erythroid, progenitor, cells])]). relacion([sujeto(['Leukemic', cells, stain, positively, with, an, 'erythroid-associated']), verbo([nuclear]), complemento([transcription, factor, '(', 'GATA-1)'])]). relacion([sujeto([ras, transgene, expression, 'is,', 'however,', detected, only, in, normal, bone, marrow, and, leukemic, tissues, of, transgenic, 'mice,', and, 5, '\'', mapping, experiments, using, 'S1', protection, analysis, of, total, 'RNA', from, leukemic, tissue, indicates, that, transcription, of, the, transgene, mRNA, is, initiated, from, the, natural, 'zeta-globin', promoter, start, 'site,', supporting, the, belief, that, the, 'zeta-globin', promoter, directs, 'v-Ha-ras', expression, in, erythroid, progenitor, 'cells,', ultimately]), verbo([leading]), complemento([to, leukemic, transformation])]). relacion([sujeto(['To', elucidate, the, contributions, of, 'GATA-1', to, definitive, hematopoiesis, in, 'vivo,', we]), verbo([have]), complemento([examined, adult, mice, that, were, rendered, genetically, defective, in, 'GATA-1', synthesis, '(', 'Takahashi', et, 'al,', 'J', 'Biol', 'Chem', 272, :, 12611, ',', 1997, ')'])]). relacion([sujeto([5, ')', 'GATA-1', 'allele,', consequently]), verbo([leading]), complemento([to, variable, anemic, severity])]). relacion([sujeto(['Proerythroblasts', and, megakaryocytes, massively, accumulated, in, the, spleens, of, the, 'heterozygotes,', and, we, showed, that, the, neomycin, resistance, gene, '(', which, is, the, positive, selection, marker, in, 'ES', 'cells)', was]), verbo([expressed]), complemento([profusely, in, the, abnormally, abundant, cells, generated, in, the, 'GATA-1'])]). relacion([sujeto(['These', data]), verbo([suggest]), complemento([that, a, small, number, of, 'GATA-1'])]). relacion([sujeto([5, mutant, hematopoietic, progenitor, cells, begin, to, proliferate, vigorously, during, early, 'adulthood,', but, because, the, cells, are, unable, to, terminally, 'differentiate,', this]), verbo([leads]), complemento([to, progenitor, proliferation, in, the, spleen, and, consequently, death])]). relacion([sujeto(['This', promoter, is, 'TATA-less,', and]), verbo([binds]), complemento([trancription, factors, of, the, 'Ets,', 'C/EBP,', 'GATA', and, 'Myb', families])]). relacion([sujeto(['The', 'Ets-1/Fli-1', and, 'C/EBPalpha', proteins, were, the, most, potent, 'activators,', and]), verbo([acted]), complemento([with, high, synergy, through, juxtaposed, binding, sites, located, approximately, 60, bp, upstream, of, the, transcription, start, site])]). relacion([sujeto(['The', 'Ets-1', and, 'C/EBPalpha', proteins, were]), verbo([found]), complemento([to, associate, physically, via, their, 'DNA-binding', domains, and, to, bind, their, combined, binding, site, cooperatively])]). relacion([sujeto(['GATA-1', showed, biphasic, regulation, of, the, 'EOS47', 'promoter,']), verbo([activating]), complemento([at, low, and, repressing, at, high, protein, concentrations])]). relacion([sujeto(['Transcription', factors]), verbo([regulating]), complemento([the, process, of, megakaryocyte, development, remain, largely, unclarified])]). relacion([sujeto(['Under', these, 'conditions,', we, analyzed, the, expression, of, the, transcription, factors, and, observed, that, the, expression, of, 'NF-E2', 'p45,', but, not, those, of, 'GATA-1,', 'GATA-2,', 'Tal-1/SCL,', 'Evi-1,', and, 'MafK,', was]), verbo([increased]), complemento([after, 'TPO', and, 'K252a', stimulation])]). relacion([sujeto(['Gel-shift', assay, confirmed, the]), verbo([enhanced]), complemento([binding, activity, to, the, 'NF-E2', site])]). relacion([sujeto(['The', abolishment, of, 'NF-E2', p45, with, 'NF-E2', antisense, oligomers]), verbo([inhibited]), complemento(['TPO', plus, 'K252a-induced', polyploidization])]). relacion([sujeto(['These', findings]), verbo([suggest]), complemento([that, 'NF-E2', p45, is, essential, for, the, polyploidization, of, megakaryocytic, cells])]). relacion([sujeto(['Erythrocyte', development]), verbo([has]), complemento([previously, been, shown, to, depend, upon, the, expression, of, the, 'lineage-restricted', 'trans-acting', factor, 'GATA-1'])]). relacion([sujeto(['Despite', predicted, roles, for, this, factor, during, early, 'development,', 'GATA-1-deficient', cells, in, chimeric, mice, and, embryonic, stem, cell, cultures, mature, to, a, late, proerythroblast, stage, and]), verbo([express]), complemento([at, least, certain, genes, that, normally, are, thought, to, be, regulated, by, 'GATA-1', '(', including, erythroid, 'Krüppel-like', factor, '[', 'EKLF]', and, the, erythropoietin, '[', 'Epo]', 'receptor)'])]). relacion([sujeto(['In', the, present, 'study,', in, an, alternate, approach, to, test, the, function, of, 'GATA-1,', 'GATA-1']), verbo([has]), complemento([been, expressed, together, with, the, 'Epo', receptor, in, myeloid, 'FDCW2', cells, and, the, resulting, effects, on, 'cytokine-dependent', proliferation, and, erythroid, gene, expression, have, been, assessed])]). relacion([sujeto(['Upon', expression, of, 'GATA-1', at]), verbo([increased]), complemento(['levels,', proliferation, in, response, to, 'Epo,', 'interleukin-3', '(', 'IL-3),', and, stem, cell, factor, was, attenuated, and, endogenous, 'GATA-1,', 'EKLF', and, 'betamaj-globin', gene, expression, was, activated])]). relacion([sujeto(['Finally,', in, 'FDCW2', cells]), verbo([expressing]), complemento([increased, levels, of, 'GATA-1', and, a, 'carboxyl-terminally', truncated, 'Epo', 'receptor,', 'Epo', '(', with, respect, to, 'IL-3', as, a, 'control)', was, shown, to, markedly, promote, globin, transcript, expression])]). relacion([sujeto(['The', solution, structure, of, a, complex, between, the, 'DNA']), verbo([binding]), complemento([domain, of, a, fungal, 'GATA', factor, and, a, 13, 'base-pair', oligonucleotide, containing, its, physiologically, relevant, 'CGATAG', target, sequence, has, been, determined, by, multidimensional, nuclear, magnetic, resonance, spectroscopy])]). relacion([sujeto(['The', 'AREA', 'DNA']), verbo([binding]), complemento(['domain,', from, 'Aspergillus', 'nidulans,', possesses, a, single, 'Cys2-Cys2', zinc, finger, module, and, a, basic, 'C-terminal', 'tail,', which, recognize, the, 'CGATAG', element, via, an, extensive, network, of, hydrophobic, interactions, with, the, bases, in, the, major, groove, and, numerous, 'non-specific', contacts, along, the, 'sugar-phosphate', backbone])]). relacion([sujeto(['The', zinc, finger, core, of, the, 'AREA', 'DNA']), verbo([binding]), complemento([domain, has, the, same, global, fold, as, that, of, the, 'C-terminal', 'DNA', binding, domain, of, chicken, 'GATA-1'])]). relacion([sujeto(['In', contrast, to, the, complex, with, the, 'DNA']), verbo([binding]), complemento([domain, of, 'GATA-1', in, which, the, basic, 'C-terminal', tail, wraps, around, the, 'DNA', and, lies, in, the, minor, 'groove,', the, structure, of, complex, with, the, 'AREA', 'DNA', binding, domain, reveals, that, the, 'C-terminal', tail, of, the, fungal, domain, runs, parallel, with, the, sugar, phosphate, backbone, along, the, edge, of, the, minor, groove])]). relacion([sujeto(['This', difference, is, principally, attributed, to, amino, acid, substitutions, at, two, positions, of, the, 'AREA', 'DNA']), verbo([binding]), complemento([domain, '(', 'Val55,', 'Asn62)', relative, to, that, of, 'GATA-1', '(', 'Gly55,', 'Lys62)'])]). relacion([sujeto(['The', impact, of, the, different, 'C-terminal', tail]), verbo([binding]), complemento([modes, on, the, affinity, and, specificity, of, 'GATA', factors, is, discussed])]). relacion([sujeto(['Granule', major, basic, protein, '(', 'MBP)', is]), verbo([expressed]), complemento([exclusively, in, 'eosinophils,', 'basophils,', and, placental, trophoblasts])]). relacion([sujeto(['To', identify, the, 'cis-elements', and, transcription, factors]), verbo([involved]), complemento([in, regulating, 'MBP', 'expression,', we, subcloned, 3.2, kb, of, sequence, upstream, of, the, exon, 9, transcriptional, start, site, '(', 'P2', 'promoter)', and, serial, 5, '\'', deletions, into, the, pXP2, luciferase, reporter, vector])]). relacion([sujeto(['To', identify, transcription, factors, that]), verbo([bind]), complemento([to, and, transactivate, through, the, bp, -, 117, to, -, 67, 'region,', we, first, compared, the, upstream, genomic, sequences, of, human, and, murine, 'MBP;', a, potential, 'GATA', binding, consensus, site, was, conserved, in, the, 50, -, bp, region, between, the, two, genes])]). relacion([sujeto(['To', determine, which, 'GATA', proteins]), verbo([bind]), complemento([this, consensus, 'site,', we, performed, electrophoretic, mobility, shift, assays, '(', 'EMSAs),', which, showed, that, both, 'GATA-1', and, 'GATA-2', can, bind, to, this, consensus, site])]). relacion([sujeto(['In', 'contrast,', combined, cotransfection, of, 'GATA-1', and, 'GATA-2']), verbo([decreased]), complemento([the, ability, of, 'GATA-1', to, transactivate, the, 'MBP', promoter, by, approximately, 50, '%'])]). relacion([sujeto(['Our', results]), verbo([provide]), complemento([the, first, evidence, for, a, 'GATA-1', target, gene, in, 'eosinophils,', a, negative, regulatory, role, for, 'GATA-2', in, 'MBP', 'expression,', and, possibly, eosinophil, gene, transcription, in, general, during, myelopoiesis])]). relacion([sujeto(['While', mast, cells]), verbo([have]), complemento([been, previously, shown, to, express, both, 'GATA-1', and, 'GATA-2', 'mRNAs,', individual, functions, for, these, related, factors, during, their, course, of, differentiation, within, the, mast, cell, lineage, have, not, yet, been, defined])]). relacion([sujeto(['GATA-2', protein, was, abundantly]), verbo([expressed]), complemento([in, all, three, mast, cell, lines, and, in, 'BMMCs,', but, only, weakly, in, some, of, 'PMCs'])]). relacion([sujeto(['In', 'contrast,', 'GATA-1', protein, was]), verbo([expressed]), complemento([in, 'PMCs', and, 'BMMCs', after, culture, in, the, presence, of, 'IL3', and, 'SCF'])]). relacion([sujeto(['We', also]), verbo([found]), complemento([the, presence, of, 'Alcian', blue, 'staining-positive', but, berberine, 'staining-negative', mast, cells, in, the, skin, of, mice, heterozygous, to, 'GATA-1', 'knock-down', allele])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, the, expression, of, 'GATA', 'factor-dependent', genes, is, regulated, by, 'GATA-2', during, mast, cell, development, and, that, 'GATA-1', is, required, for, the, specification, of, differentiated, mast, cell, phenotypes])]). relacion([sujeto(['CCR5', promoter, activity, was, 'up-regulated', by, 'PMA,', and, a, region, spanning, -, 417, to, +, 61, relative, to, the, transcription, start, site, was, sufficient, for, the, basal, and]), verbo([induced]), complemento([activity])]). relacion([sujeto(['DNase', 'I', footprinting, assays, demonstrated, several, protected, areas, within, this, 'region,', and, gel, shift, assays, determined]), verbo([binding]), complemento([sites, for, transcriptional, factors, 'Oct-1,', 'Oct-2,', 'T', cell, factor, 1, 'alpha,', and, 'GATA1'])]). relacion([sujeto(['CCR5', promoter, activity, was, also]), verbo([induced]), complemento([by, 'IL-2', or, 'anti-CD3', 'Ab,', while, stimulation, with, 'anti-CD28', 'Ab', markedly, reduced, 'CD3-mediated', 'up-regulation', of, the, 'CCR5', promoter])]). relacion([sujeto(['GATA-1']), verbo([participates]), complemento([in, the, transcription, of, virtually, all, 'erythroid-specific', 'genes,', blocks, apoptosis, of, precursor, 'cells,', and, controls, the, balance, between, proliferation, and, cell, cycle, arrest])]). relacion([sujeto(['Prior', studies]), verbo([suggest]), complemento([that, the, function, of, 'GATA-1', is, mediated, in, part, through, association, with, transcriptional, cofactors])]). relacion([sujeto(['CREB-binding', protein, '(', 'CBP)', and, its, close, relative, p300, serve, as, coactivators, for, a, variety, of, transcription, factors]), verbo([involved]), complemento([in, growth, control, and, differentiation])]). relacion([sujeto(['We']), verbo([report]), complemento([here, that, 'CBP', markedly, stimulates, 'GATA-1\'s', transcriptional, activity, in, transient, transfection, experiments, in, nonhematopoietic, cells])]). relacion([sujeto(['GATA-1', and, 'CBP', also, coimmunoprecipitate, from]), verbo([nuclear]), complemento([extracts, of, erythroid, cells])]). relacion([sujeto(['Expression', of, a, conditional, form, of, adenovirus, 'E1A', in, murine, erythroleukemia, cells, blocks, differentiation, and, expression, of, endogenous, 'GATA-1']), verbo([target]), complemento(['genes,', whereas, mutant, forms, of, 'E1A', unable, to, bind, 'CBP/p300', have, no, effect])]). relacion([sujeto(['The', collagenase, 'B', type, 'IV', '(', 'Col4B)', gene, is, highly]), verbo([expressed]), complemento([in, the, 'osteoclast,', the, primary, 'bone-resorbing', cell])]). relacion([sujeto(['However,', factors, that]), verbo([regulate]), complemento([expression, of, the, 'Col4B', gene, are, not, well, characterized])]). relacion([sujeto(['Putative', transcription, factors, such, as, 'SRY,', 'Lyf-1,', and, 'GATA1', and, 2, ',']), verbo([binding]), complemento([motifs, were, identified, by, sequence, analysis, in, this, promoter, region])]). relacion([sujeto(['This', promoter]), verbo([provides]), complemento([a, valuable, tool, for, targeting, gene, expression, to, the, osteoclast])]). relacion([sujeto(['We']), verbo([have]), complemento([previously, demonstrated, that, the, basal, transcription, of, rat, inhibin, 'alpha-subunit', gene, in, a, mouse, testicular, 'Leydig', tumor, cell, 'line,', 'MA-10,', depends, upon, a, 67, -, bp, 'DNA', fragment, at, the, position, of, -, 163, to, -, 97])]). relacion([sujeto(['Testis-specific', 'GATA-1', 'mRNA,', which, is]), verbo([transcribed]), complemento([from, a, promoter, 8, kb, upstream, to, the, erythroid, exon, 'I', of, mouse, 'GATA-1', 'gene,', was, also, identified, in, 'MA-10', cells])]). relacion([sujeto(['Mutations', of, 'GATA', sequences, in, 'alpha-subunit', promoter, markedly]), verbo([decreased]), complemento([the, transcriptional, activity, of, 'alpha-subunit', gene, when, measured, by, their, ability, of, transient, expression, of, a, bacterial, reporter, 'gene,', chloramphenicol, acetyltransferase, '(', 'CAT),', in, 'MA-10', cells])]). relacion([sujeto(['The', transactivation, by, 'GATA-1', was]), verbo([inhibited]), complemento([if, 'GATA', sequences, in, 'alpha-subunit', promoter, were, mutated])]). relacion([sujeto(['Furthermore,', electrophoretic, mobility, shift, assay, demonstrated, that, 'GATA-binding', proteins, present, in]), verbo([nuclear]), complemento([extracts, of, 'MA-10', cells, and, rat, testis, interacted, with, the, 'GATA', motifs, in, 'alpha-subunit', 'promoter,', and, the, 'GATA-1', in, these, nuclear, extracts, formed, a, supershifted, immunocomplex, with, antibody, raised, against, mouse, 'GATA-1', protein])]). relacion([sujeto(['In', 'summary,', we]), verbo([have]), complemento([provided, the, first, evidence, of, the, functional, role, of, a, 'GATA-binding', protein, in, the, regulation, of, testicular, gene, expression])]). relacion([sujeto(['Rh50', 'glyco-protein', is, the, membrane, protein, tightly]), verbo([associated]), complemento([with, 'Rh', polypeptides, and, is, critical, for, expression, of, 'Rh', antigens])]). relacion([sujeto(['The', inverse, 'GATA', motif, was, the]), verbo([target]), complemento([sequence, of, 'GATA-1', 'protein,', and, disruption, of, the, motif, abolished, the, transactivating, activity, of, erythroid, cells])]). relacion([sujeto(['These', studies, confirm, the, 'erythroid-specific', expression, of, 'Rh', 'antigens,', but]), verbo([suggest]), complemento([distinct, regulatory, mechanisms, for, 'RH', vs, 'RH50', genes])]). relacion([sujeto(['In', this, 'study,', we, investigated, the, effect, of, 'ER', alpha, '(', referred, to, throughout, as, 'ER)', on, 'DNA-binding', activities, of, transcription, factors]), verbo([involved]), complemento([in, regulating, the, expression, of, 'erythroid-specific', 'genes,', 'and,', in, 'particular,', the, histone, 'H5', gene])]). relacion([sujeto(['Using', electrophoretic, mobility, shift, 'assays,', we]), verbo([found]), complemento([that, in, the, presence, of, rabbit, reticulocyte, 'lysate,', human, 'ER', reduced, the, binding, activities, of, chicken, immature, erythrocyte, nuclear, extracted, proteins, to, 'GATA', and, 'CACCC', sites, in, the, 'H5', promoter, and, enhancer])]). relacion([sujeto(['In', 'contrast,', the]), verbo([binding]), complemento([activities, of, 'NF1', and, 'Sp1', were, not, affected, by, 'ER'])]). relacion([sujeto(['Binding', of, 'ER', to, an, estrogen, response, element, was]), verbo([enhanced]), complemento([by, addition, of, rabbit, reticulocyte, lysate])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, additional, 'factor(s)', are, necessary, for, full, 'ER', function])]). relacion([sujeto(['Both', 'GATA-1', and, 'CACCC-binding', proteins, are, critical, for, the, developmentally]), verbo([regulated]), complemento([expression, of, 'erythroid-specific', genes])]). relacion([sujeto(['We', hypothesize, that, interference, in, 'DNA-binding', activities, of, 'GATA-1', and, 'CACCC-binding', proteins, is, the, mechanism, by, which, the, 'ER']), verbo([inhibits]), complemento([regulation, of, these, genes])]). relacion([sujeto(['It', is, also]), verbo([expressed]), complemento([in, cells, of, other, hematopoietic, lineages, including, 'megakaryocytes,', mast, 'cells,', and, eosinophils])]). relacion([sujeto(['To', further, analyze, the, role, of, 'GATA-1', in, controlling, differentiation, from, hematopoietic, stem, 'cells,', we, investigated, the, phenotypic, changes]), verbo([induced]), complemento([by, the, overexpression, of, murine, 'GATA-1', in, the, murine, myeloid, leukemic, cell, 'line,', 'M1'])]). relacion([sujeto(['Forced', expression, of, 'GATA-1']), verbo([induced]), complemento([the, appearance, of, erythroid, cells, and, megakaryocytes, as, assessed, by, cellular, 'morphology,', acetylcholinesterase, 'activity,', and, expression, of, platelet, factor, 4, and, 'beta-globin', mRNA, synthesis])]). relacion([sujeto(['The', 'c-mpl', ligand, mRNA, was, equally]), verbo([expressed]), complemento([both, in, parental, 'M1', cells, and, in, those, transfected, with, the, 'GATA-1', expression, vector])]). relacion([sujeto(['In', 'contrast,', the, mRNA, expression, of, 'c-mpl', was]), verbo([increased]), complemento([only, in, 'GATA-1', expressing, 'M1', cells, differentiated, towards, erythroid, and, megakaryocyte, lineages])]). relacion([sujeto(['The']), verbo([increased]), complemento([expression, of, 'c-mpl', mRNA, induced, by, 'GATA-1', raised, the, question, as, to, whether, or, not, 'GATA-1', transactivated, the, 'c-mpl', promoter])]). relacion([sujeto(['The', activity, of, the, 'c-mpl', promoter, in, the, presence, of, cotransfected, 'GATA-1', was, significantly]), verbo([increased]), complemento([compared, with, that, of, the, control])]). relacion([sujeto(['These', findings]), verbo([suggest]), complemento([that, the, upregulation, of, 'c-mpl', induced, by, 'GATA-1', expression, in, 'M1', cells, is, closely, associated, with, erythroid, and, megakaryocytic, differentiation])]). relacion([sujeto(['Germline', transgenic, fish, obtained, from, the, injected, founders, continued, to]), verbo([express]), complemento([green, fluorescent, protein, in, erythroid, cells, in, the, 'F1', and, 'F2', generations])]). relacion([sujeto(['These', transgenic, fish]), verbo([have]), complemento([allowed, us, to, 'isolate,', by, 'fluorescence-activated', cell, 'sorting,', the, earliest, erythroid, progenitor, cells, from, developing, embryos, for, in, vitro, studies])]). relacion([sujeto(['The', 'Wilms\'', tumor, 1, gene, '(', 'WT1)', encodes, a, 'zinc-finger', transcription, factor, which, is]), verbo([expressed]), complemento([in, a, 'tissue-specific', manner])]). relacion([sujeto(['Our', studies, indicate, that, in, addition, to, the, 'promoter,', other, regulatory, elements, are]), verbo([required]), complemento([for, 'tissue-specific', expression, of, this, gene])]). relacion([sujeto(['A', 258, -, base, pair, hematopoietic, specific, enhancer, in, intron, 3, of, the, 'WT1', gene]), verbo([increased]), complemento([the, transcriptional, activity, of, the, 'WT1', promoter, by, 8, -, 10, -, fold, in, 'K562', and, 'HL60', cells])]). relacion([sujeto(['Mutation', of, the, 'GATA', motif]), verbo([decreased]), complemento([the, enhancer, activity, by, 60, '%', in, 'K562', cells])]). relacion([sujeto(['Electrophoretic', mobility, shift, assays, showed, that, the, 'GATA-1', protein, in, 'K562']), verbo([nuclear]), complemento([extracts, binds, to, this, motif])]). relacion([sujeto(['Cotransfection', of, the, enhancer, containing, reporter, construct, with, a, 'GATA-1', expression, vector, showed, that, 'GATA-1', transactivated, this, 'enhancer,']), verbo([increasing]), complemento([the, 'CAT', reporter, activity, 10, -, 15, -, fold])]). relacion([sujeto(['A', 'DNase', 'I-hypersensitive', site]), verbo([has]), complemento([also, been, mapped, in, the, 258, -, base, pair, enhancer, region])]). relacion([sujeto(['These', data]), verbo([suggest]), complemento([that, 'GATA-1', and, 'c-Myb', are, responsible, for, the, activity, of, this, enhancer, in, hematopoietic, cells, and, may, bind, to, the, enhancer, in, vivo])]). relacion([sujeto(['Butyric', acid, '(', 'BA)', was, shown, to]), verbo([induce]), complemento([hemoglobinization, of, 'K562', cells, in, a, 'dose-', and, 'time-dependent', manner])]). relacion([sujeto(['The', maximal, differentiation, '(', 54, '%', of, hemoglobinized, 'cells)', was, obtained, with, the, 0.5, mM, 'concentration,', which]), verbo([induced]), complemento([a, 60, '%', inhibition, of, cell, growth, at, day, 3, without, cytotoxicity])]). relacion([sujeto(['Parallel', to, the, kinetics, of, 'hemoglobinization,', a, rapid]), verbo([increase]), complemento([in, 'gamma-globin', and, porphobilinogen, deaminase, '(', 'PBGD)', mRNAs, was, observed, in, 'BA-treated', cells])]). relacion([sujeto(['This']), verbo([increase]), complemento([was, 'time-dependent', and, higher, for, 'gamma-globin', than, for, 'PBGD', '(', 'six-', and, 'two-fold', at, day, 3, ',', 'respectively)'])]). relacion([sujeto(['Analysis', of, erythroid, transcription, factor, mRNA, levels, during, the, time, course, of, 'BA', treatment, 'showed,', for, the, first, 'time,', an, early, and, marked, '(', up, to, 'three-fold)']), verbo([increase]), complemento([in, p45, 'NF-E2', 'mRNA,', contrasting, with, that, of, 'GATA-1', mRNA, '(', &, 'lt;1'])]). relacion([sujeto(['Taken', 'together,', these, results, showed, the, rapid, differentiating, effect, of, 'BA', and]), verbo([suggest]), complemento([the, involvement, of, the, 'NF-E2', transcription, factor])]). relacion([sujeto(['The', 'Wilms\'-tumor', gene, 'WT1', may]), verbo([have]), complemento([a, different, function, from, a, 'tumor-suppressor', gene, in, some, leukemias])]). relacion([sujeto(['Using', the, 7, ',', 12, -, 'dimethylbenz[a]anthracene', '(', 'DMBA)-induced', rat, leukemia, 'system,', we, examined, whether, 'WT1', expression, was]), verbo([involved]), complemento([during, 'leukemogenesis,', since, this, model, enabled, us, to, analyze, cells, altered, by, 'DMBA', at, various, stages, of, leukemogenesis])]). relacion([sujeto(['Among', 15, 'WT1-expressing', 'leukemias,', 'GATA-1,', which, is, an, 'erythroid-specific', transcription, factor, and, might]), verbo([regulate]), complemento(['WT1', 'expression,', was, also, expressed, in, 13, cases, '(', p, &, 'lt;', 0.05, ')'])]). relacion([sujeto(['These', results, showed, that, cells, with, a, high, expression, level, of, 'WT1', tended, to, develop, into, leukemia, and, that, 'WT1', contributed, to, leukemogenesis, in, the, late, 'stage,']), verbo([suggesting]), complemento([that, the, expression, of, 'WT1', plays, an, important, role, in, cell, proliferation, and, in, maintaining, the, viability, of, some, leukemia, cells])]). relacion([sujeto(['The', transcription, factor, 'GATA-1,', which, is]), verbo([expressed]), complemento([in, several, hematopoietic, lineages, and, multipotential, 'progenitors,', is, required, for, the, development, of, red, blood, cells, and, platelets])]). relacion([sujeto(['Transgenes', with, 2.7, kb, of, promoter, sequences, are]), verbo([expressed]), complemento([infrequently, and, only, within, adult, '(', 'definitive)', erythroid, cells])]). relacion([sujeto(['We', show, that, inclusion, of, an, upstream, hypersensitive, site, '(', 'HS', 'I)', markedly]), verbo([enhances]), complemento([the, frequency, of, expressing, transgenic, lines, and, activates, expression, in, primitive, erythroid, cells])]). relacion([sujeto(['By', breeding, a, 'GATA-1/lacZ', transgene, into, a, 'GATA-1(-)', 'background,', we, also]), verbo([have]), complemento([shown, that, the, activation, or, maintenance, of, 'GATA-1', expression, does, not, require, the, presence, of, 'GATA-1', 'itself,', thereby, excluding, simple, models, of, positive, autoregulation])]). relacion([sujeto(['The', transgene, cassette]), verbo([reported]), complemento([here, should, be, useful, in, directing, expression, of, foreign, sequences, at, the, onset, of, hematopoiesis, in, the, embryo, and, may, assist, in, the, identification, of, upstream, regulators, of, the, 'GATA-1', gene])]). relacion([sujeto(['Using', the]), verbo([conserved]), complemento([zinc, finger, 'DNA-binding', domain, of, 'GATA-1', in, the, yeast, 'two-hybrid', 'system,', we, have, identified, a, 'novel,', multitype, zinc, finger, 'protein,', 'Friend', of, 'GATA-1', '(', 'FOG),', which, binds, 'GATA-1', but, not, a, functionally, inactive, mutant, lacking, the, amino, '(', 'N)', finger])]). relacion([sujeto(['Furthermore,', 'FOG', and, 'GATA-1', synergistically]), verbo([activate]), complemento([transcription, from, a, 'hematopoietic-specific', regulatory, region, and, cooperate, during, both, erythroid, and, megakaryocytic, cell, differentiation])]). relacion([sujeto(['These', findings, indicate, that, 'FOG']), verbo([acts]), complemento([as, a, cofactor, for, 'GATA-1', and, provide, a, paradigm, for, the, regulation, of, cell, 'type-specific', gene, expression, by, 'GATA', transcription, factors])]). relacion([sujeto(['GATA-1', is, also]), verbo([expressed]), complemento([in, 'megakaryocytes,', mast, 'cells,', 'eosinophils,', multipotential, hematopoietic, progenitors, and, 'Sertoli', cells, of, the, 'testis,', where, its, functions, have, been, elusive])]). relacion([sujeto(['This', resulted, in, generation, of, mice, with, selective]), verbo([loss]), complemento([of, megakaryocyte, 'GATA-1', 'expression,', yet, sufficient, erythroid, cell, levels, to, avoid, lethal, anemia])]). relacion([sujeto(['The', mutant, mice]), verbo([have]), complemento([markedly, reduced, platelet, 'numbers,', associated, with, deregulated, megakaryocyte, proliferation, and, severely, impaired, cytoplasmic, maturation])]). relacion([sujeto(['These', findings]), verbo([reveal]), complemento([a, critical, role, for, 'GATA-1', in, megakaryocyte, growth, regulation, and, platelet, 'biogenesis,', and, illustrate, how, targeted, mutation, of, 'cis-elements', can, generate, 'lineage-specific', knockout, mice])]). relacion([sujeto(['The', 'hematopoietic-restricted', transcription, factor, 'GATA-1', is]), verbo([required]), complemento([for, both, mammalian, erythroid, cell, and, megakaryocyte, differentiation])]). relacion([sujeto(['Studies', of, the, consequences, of, these]), verbo([targeted]), complemento([mutations, provide, novel, insights, into, 'GATA-1', function, in, erythroid, cells])]). relacion([sujeto(['First,', the, neoDeltaHS, mutation]), verbo([leads]), complemento([to, a, marked, impairment, in, the, rate, or, efficiency, of, erythroid, cell, maturation, due, to, a, modest, '(', 4, -, to, 5, -, 'fold)', decrease, in, 'GATA-1', expression])]). relacion([sujeto(['Finally,', despite, the, potency, of, the, upstream, sequences, in]), verbo([conferring]), complemento(['high-level,', developmentally, appropriate, expression, of, transgenes, in, 'mice,', other, 'cis-regulatory', elements, within, the, 'GATA-1', compensate, for, its, absence, in, erythroid, cells])]). relacion([sujeto(['Our', work, illustrates, the, usefulness, of]), verbo([targeted]), complemento([mutations, to, create, knockdown, mutations, that, may, uncover, important, quantitative, contributions, of, gene, function, not, revealed, by, conventional, knockouts])]). relacion([sujeto(['We']), verbo([have]), complemento(['investigated,', by, semiquantitative, 'RT-PCR,', the, kinetics, of, activation, of, hematopoietic, receptors, and, differentiation, markers, in, partially, purified, murine, hematopoietic, stem, cells, '(', 'HSC)', induced, to, differentiate, in, 'serum-free', culture, with, combinations, of, growth, factor, '(', 'GF)'])]). relacion([sujeto(['The', following, pattern, of, expression, was, 'observed:', the, alpha, subunit, of, the, 'IL-3', receptor, clearly, was]), verbo([expressed]), complemento([in, both, 'Rho-bright', and, 'Rho-dull', cells, at, the, 'outset,', and, its, expression, did, not, change, over, time, in, culture])]). relacion([sujeto(['The', beta, subunits, of, the, 'IL-3', and, 'GM-CSF', 'receptor,', the, alpha, subunit, of, the, 'GM-CSF', 'receptor,', the, 'Epo', and, 'G-CSF', receptors, and, 'Fms', barely, were]), verbo([expressed]), complemento([in, purified, 'Rho-bright', and, 'Rho-dull', 'cells,', but, their, expression, increased, in, cells, cultured, both, in, erythroid, and, in, myeloid, 'GF', combinations])]). relacion([sujeto(['Gata1', was]), verbo([expressed]), complemento([maximally, in, 'Rho-bright', cells, but, was, below, the, level, of, detection, in, 'Rho-dull', cells])]). relacion([sujeto(['Rho-dull', cells]), verbo([expressed]), complemento(['Gata1', when, cultured, both, in, erythroid, and, in, myeloid, 'GF', combinations])]). relacion([sujeto(['In', 'contrast,', 'alpha-', and, 'beta-globin,', which, also, were, not]), verbo([expressed]), complemento([in, the, purified, 'cells,', were, induced, only, in, cells, stimulated, with, 'Epo'])]). relacion([sujeto(['These', results, indicate, that, the, genes, for, all, the, 'GF', receptors, investigated, '(', with, the, exception, of, the, alpha, subunit, of, the, 'IL-3', 'receptor)', are]), verbo([expressed]), complemento([at, low, 'levels,', if, 'any,', in, purified, 'Rho-bright', or, 'Rho-dull', 'cells,', but, are, expressed, in, their, progeny, cultured, either, in, erythroid, or, myeloid, 'GF', combinations])]). relacion([sujeto(['The', expression, of, the, 'Epo', 'receptor,', in, 'particular,', is]), verbo([activated]), complemento([both, in, erythroid, '(', 'alpha-', and, 'beta-globin', positive, and, in, myeloid, '(', 'alpha-', and, 'beta-globin', 'negative)', cells])]). relacion([sujeto(['Male', offspring, of, chimeras, bearing, the]), verbo([targeted]), complemento([mutation, were, found, to, die, by, 12.5, days, post, coitus, due, to, severe, anemia, while, heterozygous, females, displayed, characteristics, ranging, from, severe, anemia, to, normal, erythropoiesis])]). relacion([sujeto(['When', female, heterozygotes, were, crossed, with, transgenic, males, carrying, a, reporter, 'gene,', which, specifically, marks, primitive, erythroid, 'progenitors,', massive, accumulation, of, undifferentiated, erythroid, cells, were, observed, in, the, yolk, sacs, of, the, 'GATA-1-mutant', 'embryos,', demonstrating, that, 'GATA-1', is]), verbo([required]), complemento([for, the, terminal, differentiation, of, primitive, erythroid, cells, in, vivo])]). relacion([sujeto(['Transcription', factor, 'GATA-1', is]), verbo([required]), complemento([for, the, terminal, differentiation, of, both, the, primitive, and, definitive, erythroid, cell, 'lineages,', and, yet, the, regulatory, mechanisms, of, 'GATA-1', itself, are, not, well, understood])]). relacion([sujeto(['We']), verbo([found]), complemento([that, a, transcriptional, control, element, located, between, -, 3.9, and, -, 2.6, kb, 5, '\'', to, the, erythroid, first, exon, serves, as, an, activating, element, and, that, this, sequence, alone, is, sufficient, to, recapitulate, the, expression, of, 'GATA-1', '(', but, uniquely, in, primitive, erythroid, 'cells)'])]). relacion([sujeto(['Addition', of, sequences, from, the, 'GATA-1', first, intron, to, this, upstream, element]), verbo([provides]), complemento([a, necessary, and, sufficient, condition, for, complete, recapitulation, of, 'GATA-1', expression, in, both, primitive, and, definitive, erythroid, cells])]). relacion([sujeto(['The', first, intron, element, does, not, possess, intrinsic, transcriptional, activation, potential, when, linked, to, the, 'GATA-1', gene, promoter, but, rather]), verbo([requires]), complemento([the, upstream, activating, element, for, its, activity])]). relacion([sujeto(['These', experiments, show, that, 'GATA-1', gene, expression, is]), verbo([regulated]), complemento([by, discrete, transcriptional, control, elements, during, definitive, and, primitive, 'erythropoiesis:', 'The', 5, '\'', element, displays, properties, anticipated, for, a, primitive, erythroid, 'cell-specific', activating, 'element,', and, the, novel, element, within, the, 'GATA-1', first, intron, specifically, augments, this, activity, in, definitive, erythroid, cells])]). relacion([sujeto([3.3, ')', ',', the, sixth, enzyme, of, heme, 'biosynthesis,']), verbo([transcribed]), complemento([from, a, single, promoter, is, markedly, induced, during, erythroid, differentiation])]). relacion([sujeto(['CPO', is, ubiquitously]), verbo([expressed]), complemento([in, all, cells])]). relacion([sujeto(['To', determine, 'cis-acting', elements, of, the, human, 'CPO', 'gene,', the, promoter, region, of, the, gene, was, 'isolated,', and, three, potential, 'GATA-1', motifs, and, four, 'GC', boxes, were]), verbo([found]), complemento([within, this, fragment])]). relacion([sujeto(['In', a, functional, analysis, of, various, deletion, 'mutants,', we]), verbo([found]), complemento([that, the, 'GATA-1', binding, site, at, -, 143, to, -, 138, was, essential, for, basic, and, inducible, expressions, of, the, 'CPO', gene, in, mouse, erythroleukemia, '(', 'MEL)', cells])]). relacion([sujeto(['Gel', mobility, shift, assay, revealed, that, 'GATA-1']), verbo([bound]), complemento([to, the, region, is, required, for, the, expression, and, this, was, confirmed, by, observations, that, the, nuclear, protein, bound, to, the, 'GATA-1', motif, was, supershifted, with, anti, 'GATA-1', 'antibody,', by, gel, mobility, shift, assay])]). relacion([sujeto(['Furthermore,', 'co-expression', of, mouse, 'GATA-1', in, 'MEL', cells]), verbo([led]), complemento([to, an, increase, in, the, promoter, 'activity,', which, was, markedly, increased, by, dimethyl, 'sulfoxide-treatment'])]). relacion([sujeto(['Microcell', fusion, is, a, versatile, technique, which]), verbo([has]), complemento([been, utilized, in, characterizing, and, mapping, genes, involved, in, tumor, 'suppression,', cell, 'senescence,', and, certain, aspects, of, differentiation])]). relacion([sujeto(['Microcell', fusion]), verbo([has]), complemento([the, potential, to, contribute, to, the, understanding, of, hematopoietic, 'differentiation;', 'however,', application, of, this, technique, is, limited, by, the, need, to, use, adherent, cells, as, microcell, 'donors,', by, the, need, to, tag, candidate, chromosomes, with, a, selectable, 'marker,', and, by, the, need, for, prolonged, selection, of, fused, cells, prior, to, characterization, of, their, phenotype])]). relacion([sujeto(['We']), verbo([found]), complemento([that, microcell, fusion, induced, the, nonerythroid, recipient, cells, to, express, 'alpha-globin', mRNA, in, a, 'dose-dependent', manner])]). relacion([sujeto(['They', also]), verbo([expressed]), complemento(['RNA', for, 'beta-globin,', 'GATA-1,', and, 'NF-E2'])]). relacion([sujeto(['We', conclude, that, microcells, from, erythroid, cells, contain, all, the, information, necessary, to]), verbo([induce]), complemento([expression, of, multiple, erythroid, genes])]). relacion([sujeto(['A', possible, role, for, 'Lmo2', in, transcription, during, erythropoiesis]), verbo([has]), complemento([been, investigated])]). relacion([sujeto(['This', data]), verbo([suggest]), complemento([that, variations, in, amounts, of, complexes, involving, 'Lmo2,', 'Tall,', and, 'GATA-1', could, be, important, for, erythroid, differentiation])]). relacion([sujeto(['The', 'DLX', gene, family, is, a, family, of, divergent, homeobox, genes, which, are, related, to, the, 'Drosophila', 'distal-less', '(', 'Dll)', gene, and]), verbo([has]), complemento([been, reported, to, be, expressed, primarily, in, the, forebrain, and, craniofacial, structures])]). relacion([sujeto(['We']), verbo([have]), complemento([previously, identified, a, new, member, of, this, 'family,', 'DLX-7'])]). relacion([sujeto(['We', now]), verbo([report]), complemento([that, this, gene, is, expressed, in, normal, hematopoietic, cells, and, leukemia, cell, lines, with, erythroid, characteristics])]). relacion([sujeto(['We', used, an, antisense, oligonucleotide]), verbo([targeted]), complemento([against, the, translation, start, site, of, 'DLX-7', mRNA, to, inhibit, its, expression, in, a, human, erythroleukemia, cell, line, 'K562,', which, expresses, 'DLX-7', at, a, high, level])]). relacion([sujeto(['Inhibition', of, 'DLX-7', expression]), verbo([decreased]), complemento([the, plating, efficiency, by, approximately, 70, '%', compared, with, control])]). relacion([sujeto(['The', antisense, treatment]), verbo([caused]), complemento(['apoptosis,', as, shown, by, the, terminal, deoxynucleotidyl, 'transferase-mediated', deoxyuridine, 'triphosphate-digoxigenin', nick, end, labeling, '(', 'TUNEL)', method])]). relacion([sujeto(['Down-regulation', of, 'DLX-7', expression, by, antisense, treatment, was]), verbo([associated]), complemento([with, a, reduction, in, 'GATA-1', and, 'c-myc', mRNA, levels])]). relacion([sujeto(['Thus,', we, conclude, that, 'DLX-7', is]), verbo([expressed]), complemento([in, hematopoietic, cells, and, that, the, inhibition, of, its, expression, results, in, the, decreased, levels, of, 'GATA-1', and, 'c-myc', 'genes,', with, an, accompanying, induction, of, apoptosis])]). relacion([sujeto(['To', test, whether, human, 'GATA-1', '(', 'hGATA-1)', is]), verbo([involved]), complemento([in, the, transcriptional, control, of, globin, gene, 'switching,', we, produced, transgenic, mice, overexpressing, 'hGATA-1,', crossed, them, with, mice, carrying, a, human, 'beta-globin', locus, yeast, artificial, chromosome, '(', beta, 'YAC),', and, analyzed, globin, gene, expression, in, their, progeny])]). relacion([sujeto(['Mice', carrying, both, the, 'hGATA-1', and, the, beta, 'YAC', transgenes, had, normal, levels, of, 'gamma-', and, 'beta-globin', mRNA, and, no, distortion, in, the, rate, or, in, the, timing, of, 'gamma-to-beta', 'switch,', indicating, that, 'hGATA-1', is, not]), verbo([involved]), complemento([in, the, developmental, control, of, 'gamma-', and, 'beta-globin', genes])]). relacion([sujeto(['These', results]), verbo([provide]), complemento([direct, in, vivo, evidence, that, 'hGATA-1', is, a, specific, repressor, of, human, epsilon, gene, expression])]). relacion([sujeto(['Our', findings, also]), verbo([suggest]), complemento([that, binary, transgenic, mouse, systems, based, on, overexpression, of, transcriptional, factors, can, be, used, to, investigate, the, trans, control, of, human, globin, gene, switching])]). relacion([sujeto(['EVI1,', located, at, chromosome, band, 3, 'q26,', encodes, a, 1051, amino, acid, zinc, finger, protein, inappropriately]), verbo([expressed]), complemento([in, the, leukemic, cells, of, 2, -, 5, '%', of, acute, myeloid, leukemia, '(', 'AML)', and, myelodysplastic, syndrome, '(', 'MDS)', patients])]). relacion([sujeto(['The', activation, of, 'EVI1', often, follows, a, chromosomal, rearrangement]), verbo([involving]), complemento([band, 3, 'q26,', and, the, two, most, frequent, rearrangements, are, the, 't(3;3)(q21;q26)', and, the, 'inv(3)(q21q26)'])]). relacion([sujeto(['Both', genes, are]), verbo([expressed]), complemento([at, very, low, levels, in, the, normal, bone, marrow])]). relacion([sujeto(['The', majority, of, the, chromosomal, breakpoints, at, the, 5, '\'', end, of, 'EVI1', in, the, 't(3;3)', resulting, in, 'EVI1', activation]), verbo([have]), complemento([been, mapped, in, this, region])]). relacion([sujeto(['As', a, consequence, of, the, 't(3;3),', the, cell, would, be, unable, to]), verbo([express]), complemento(['MDS1/EVI1,', although, it, would, express, 'EVI1'])]). relacion([sujeto(['We']), verbo([have]), complemento([compared, the, transcriptional, activity, of, 'MDS1/EVI1', and, 'EVI1,', and, we, show, that, 'MDS1/EVI1', is, a, strong, activator, of, promoters, containing, the, 'AGATA', 'motif,', whereas, 'EVI1', is, a, repressor])]). relacion([sujeto(['We']), verbo([have]), complemento([also, examined, the, relative, expression, of, the, two, genes, in, normal, bone, marrow, and, in, the, bone, marrow, of, leukemia, patients, with, 3, q26, rearrangements])]). relacion([sujeto(['We', propose, that, rearrangements, at, 3, q26]), verbo([involving]), complemento(['EVI1', could, result, in, leukemia, by, a, 'two-step', process, involving, first, transcriptional, disruption, of, 'MDS1/EVI1,', and, next, by, inappropriately, activating, expression, of, 'EVI1'])]). relacion([sujeto(['Patients', with, myelodysplastic, syndrome, '(', 'MDS)']), verbo([have]), complemento([ineffective, in, vivo, and, in, vitro, 'erythropoiesis,', characterized, by, an, impaired, response, to, erythropoietin, '(', 'Epo)'])]). relacion([sujeto(['Epo-dependent', 'DNA', synthesis, as, well, as, induction, of, 'GATA-1']), verbo([binding]), complemento([activity, in, marrow, cells, from, 15, 'MDS', cases, were, severely, reduced, as, compared, with, normal, bone, marrow, '(', 'NBM)'])]). relacion([sujeto(['Additionally,', the, appearance, of, morphologically, identifiable, erythroid, cells, was]), verbo([decreased]), complemento([in, 'MDS', cell, cultures])]). relacion([sujeto(['In', all, 15, 'MDS', samples, 'tested,', 'STAT5', activation, was, absent, or, greatly]), verbo([suppressed]), complemento([in, response, to, 'Epo'])]). relacion([sujeto(['In', 'contrast,', 'interleukin-3']), verbo([induced]), complemento([a, normal, 'STAT5', response, in, 'MDS', cells])]). relacion([sujeto(['In', its, 'absence,', committed, erythroid, precursors]), verbo([arrest]), complemento([at, the, proerythroblast, stage, of, development, and, undergo, apoptosis])]). relacion([sujeto(['At', least, two, major, differences, were, established, between, domains]), verbo([required]), complemento([in, 'G1E', cells, and, those, required, in, nonhematopoietic, cells])]). relacion([sujeto(['Second,', the, amino, '(', 'N)', zinc, 'finger,', which, is, nonessential, for]), verbo([binding]), complemento([to, the, vast, majority, of, 'GATA', 'DNA', 'motifs,', is, strictly, required, for, 'GATA-1-mediated', erythroid, differentiation])]). relacion([sujeto(['Our', data]), verbo([lead]), complemento([us, to, propose, a, model, in, which, a, nuclear, 'cofactor(s)', interacting, with, the, 'N-finger', facilitates, transcriptional, action, by, 'GATA-1', in, erythroid, cells])]). relacion([sujeto(['Platelet/endothelial', cell, adhesion, 'molecule-1', '(', 'PECAM-1)', is, a, 130, -, kD, member, of, the, 'Ig', gene, superfamily, that, is]), verbo([expressed]), complemento([on, 'platelets,', endothelial, 'cells,', and, certain, leukocyte, subsets])]). relacion([sujeto(['Analysis', of, the, sequence, immediately, upstream, from, the, transcription, initiation, site, '(', 'TIS)', showed, no, canonical, 'TATA', or, 'CAAT', 'elements,', however, an, initiator, element, commonly]), verbo([found]), complemento([in, 'TATA-less', promoters, encompassed, the, 'TIS'])]). relacion([sujeto(['Putative', 'cis-acting', control, elements, present, within, a, 300, -, bp, core, promoter, included, two, ets, 'sites,', an, 'Sp1', 'site,', tandem, 'E-box', 'domains,', two, 'GATA-associated', sites, '(', 'CACCC),', an, 'AP-2']), verbo([binding]), complemento(['site,', and, a, 'GATA', element, at, -, 24])]). relacion([sujeto(['Mutational', analysis, showed, that, optimal, transcriptional, activity]), verbo([required]), complemento([the, 'GATA', sequence, at, position, -, 24, ',', and, 'gel-shift', assays, further, showed, that, the, 'GATA-2', transcription, 'factor,', but, not, 'GATA-1,', bound, to, this, region, of, the, 'PECAM-1', promoter])]). relacion([sujeto(['Understanding', the, 'cis-', and, transacting, factors, that]), verbo([regulate]), complemento([the, 'tissue-specific', expression, of, 'PECAM-1', should, increase, our, understanding, of, the, mechanisms, by, which, 'vascular-specific', gene, expression, is, achieved])]). relacion([sujeto(['We']), verbo([found]), complemento([that, the, treatment, of, 'UT-7', cells, with, 'EPO', resulted, in, a, transient, decrease, of, the, 'EPOR', mRNA, level])]). relacion([sujeto(['This', transient, downregulation, was, also]), verbo([induced]), complemento([by, stimulation, with, 'granulocyte-macrophage', 'colony-stimulating', factor, '(', 'GM-CSF),', another, stimulator, of, 'UT-7', cell, growth])]). relacion([sujeto(['Moreover,', it, was]), verbo([found]), complemento([that, 'EPO-induced', downregulation, of, 'EPOR', mRNA, level, was, preceded, by, a, transient, downregulation, of, 'GATA-1', mRNA])]). relacion([sujeto(['Both', 'EPOR', and, 'GATA-1', mRNA, 'levels,', but, not, the, 'GATA-2', mRNA, 'level,', concomitantly]), verbo([decreased]), complemento([at, the, 'G0/G1', phase, and, increased, at, the, 'S', and, 'G2/M', phases])]). relacion([sujeto(['These', findings]), verbo([suggest]), complemento([that, the, regulation, of, 'EPOR', mRNA, level, is, mainly, associated, with, 'GATA-1', gene, expression, in, 'UT-7', cells, undergoing, 'proliferation,', and, that, these, serial, events, are, under, the, control, 'of,', or, related, 'to,', the, cell, cycle])]). relacion([sujeto(['VYS', erythropoiesis, is]), verbo([decreased]), complemento([or, abrogated, by, targeted, disruption, of, the, hematopoietic, transcription, factors, 'tal-1,', 'rbtn2,', 'GATA-1,', and, 'GATA-2'])]). relacion([sujeto(['Each', of, these, genes, was]), verbo([expressed]), complemento([in, extraembryonic, 'mesoderm,', from, which, blood, islands, are, derived])]). relacion([sujeto(['GATA-1', is, a, transcription, factor]), verbo([expressed]), complemento([both, in, the, hematopoietic, system, and, in, the, 'Sertoli', cells, of, the, 'testis,', and, is, essential, for, correct, erythropoiesis])]). relacion([sujeto(['Hematopoietic', and, 'Sertoli', cells]), verbo([transcribe]), complemento(['GATA-1', from, two, different, 'promoters:', the, proximal, '(', 'erythroid)', is, active, in, hematopoietic, 'cells;', the, distal, '(', 'testis)', is, active, in, 'Sertoli', cells])]). relacion([sujeto(['We', investigated, by, 'RT-PCR', the, possibility, that, 'GATA-1', might, be]), verbo([transcribed]), complemento([from, the, testis, promoter, also, in, hematopoietic, cells])]). relacion([sujeto(['Purified', multipotent, 'progenitors,', fractionated, into, populations]), verbo([expressing]), complemento([low, or, high, levels, of, 'GATA-1,', do, not, contain, any, &, 'quot;testis"', transcripts])]). relacion([sujeto(['However,', when, grown, in, 'vitro,', they, rapidly]), verbo([express]), complemento(['GATA-1', from, the, testis, promoter, in, the, presence, of, 'Erythropoietin', '(', 'Epo)', but, not, in, that, of, other, growth, factors])]). relacion([sujeto(['Indeed,', immortalized, progenitor, cell, lines, which]), verbo([respond]), complemento([to, both, 'Epo', and, 'SCF,', continue, to, express, 'testis-derived', transcripts, when, switched, from, 'Epo', to, 'SCF'])]). relacion([sujeto(['We']), verbo([have]), complemento([utilized, 'Aspergillus', nidulans, as, a, model, system, for, the, characterization, of, the, major, vertebrate, transcription, factor, 'GATA-1'])]). relacion([sujeto(['This']), verbo([has]), complemento([been, achieved, both, by, analysing, the, function, of, murine, 'GATA-1', directly, and, by, using, direct, gene, replacement, to, introduce, chimaeric, 'areA::GATA-1', derivatives, at, the, areA, 'locus,', which, encodes, a, 'GATA', factor, involved, in, regulating, nitrogen, metabolism, in, 'A'])]). relacion([sujeto(['Although', 'GATA-1', shows, only, limited, function, when]), verbo([expressed]), complemento([in, 'A'])]). relacion([sujeto(['nidulans,', the, 'C-terminal', 'GATA', 'DNA-binding', domain, can, replace, the, native, 'GATA', domain, of, 'AREA', and]), verbo([retain]), complemento([near, 'wild-type', function])]). relacion([sujeto(['Surprisingly,', inclusion, of, the, 'N-terminal', 'DNA-binding', domain, of, 'GATA-1']), verbo([has]), complemento([a, major, role, in, determining, the, function, of, 'areA::GATA', constructs, in, 'vivo,', leading, to, a, general, loss, of, activation])]). relacion([sujeto([nidulans, as, a, model, system, for, the, molecular, and, genetic, characterization, of, heterologous, 'GATA', factors, while, also]), verbo([providing]), complemento([insights, into, native, 'Aspergillus', regulatory, components])]). relacion([sujeto(['It', is]), verbo([expressed]), complemento([predominantly, in, erythrocytes])]). relacion([sujeto(['Consensus']), verbo([binding]), complemento([sites, for, 'GATA-1', have, been, found, in, the, regulatory, elements, of, all, 'erythroid-specific', genes, examined])]). relacion([sujeto(['GATA-1', protein, is]), verbo([required]), complemento([for, erythroid, differentiation, beyond, the, proerythroblast, stage])]). relacion([sujeto(['Hence,', there, is, no, induction, of, globin, gene, transcription, and, the, cells, do, not]), verbo([arrest]), complemento([in, the, 'G1', phase, of, the, cell, cycle])]). relacion([sujeto(['To']), verbo([gain]), complemento([insight, into, the, mechanism, of, this, 'effect,', we, studied, the, levels, and, activities, of, regulators, of, 'cell-cycle', progression, during, 'DMSO-induced', differentiation])]). relacion([sujeto(['A']), verbo([decrease]), complemento([in, cyclin, 'D-dependent', kinase, activity, was, observed, during, the, induction, of, both, control, and, 'GATA-1-overexpressing', 'MEL', cells])]). relacion([sujeto(['However,', cyclin, 'E-dependent', kinase, activity]), verbo([decreased]), complemento([more, than, 20, -, fold, in, control, but, less, than, 2, -, fold, in, 'GATA-1-overexpressing', 'MEL', cells, upon, induction])]). relacion([sujeto(['Thus', 'GATA-1', may, exert, its, effects, by]), verbo([regulating]), complemento([cyclin, 'E-dependent', kinase, activity])]). relacion([sujeto(['We', also, show, that, 'GATA-1']), verbo([binds]), complemento([to, the, retinoblastoma, protein, in, 'vitro,', but, not, to, the, related, protein, 'p107,', which, may, indicate, that, 'GATA-1', interacts, directly, with, specific, members, of, the, 'cell-cycle', machinery, in, vivo])]). relacion([sujeto(['We', conclude, that, 'GATA-1']), verbo([regulates]), complemento([cell, 'fate,', in, terms, of, differentiation, or, 'proliferation,', by, affecting, the, 'cell-cycle', apparatus])]). relacion([sujeto(['To', elucidate, the, regulatory, mechanisms, underlying, the, erythroid, gene, 'regulation,', it, is, essential, to, understand, how, individual, transcription, factors, contribute, to, the, regulation, of, specific]), verbo([target]), complemento(['genes,', and, how, these, erythroid, transcription, factor, genes, are, regulated, in, turn])]). relacion([sujeto(['These', key, issues, of, mammalian, development]), verbo([have]), complemento([been, addressed, by, examining, the, activities, controlling, the, prototype, transcription, 'factor,', 'GATA-1'])]). relacion([sujeto(['The', transcriptional, regulation, of, 'GATA-1']), verbo([has]), complemento([been, intensively, 'investigated,', thereby, leading, to, the, identification, of, its, developmental, 'stage-specific', regulatory, sequences])]). relacion([sujeto(['Loss-of-function', mutant, 'animals,', combined, with, specific, marking, of, the, primitive, and, definitive, erythroid, lineages]), verbo([have]), complemento([also, shed, new, insight, into, how, 'GATA-1', activity, is, required, in, vivo, at, specific, developmental, stages])]). relacion([sujeto(['Procedures']), verbo([have]), complemento([also, been, developed, for, ascertaining, whether, or, not, the, 'GATA-1', protein, actually, binds, in, vivo, to, regulatory, 'GATA', motifs, in, candidate, target, genes])]). relacion([sujeto(['Transcription', factor, 'GATA-1', was, first, identified, in, erythroid, 'cells,', but, was, later, shown, to, also, be]), verbo([expressed]), complemento([in, 'Sertoli', cells, of, the, mouse, testis])]). relacion([sujeto(['GATA-1', transcription, in, testis, initiates, from, a, different, first, exon, '(', exon, 'IT)', than, the, erythroid, mRNA, '(']), verbo([transcribed]), complemento([from, exon, 'IE)'])]). relacion([sujeto(['To', begin, to, address, the, question, of, how, expression, of, 'GATA-1', might, be, differentially]), verbo([regulated]), complemento([in, 'Sertoli', and, erythroid, 'cells,', we, have, cloned, and, determined, the, structure, of, the, 'IT', promoters, of, both, the, rat, and, mouse, 'GATA-1', genes])]). relacion([sujeto(['Two', 'GATA']), verbo([binding]), complemento([sites, in, the, 'IT', promoter, were, found, to, be, required, for, 'GATA', 'factor-mediated', activation, in, 'fibroblasts:', 'GATA-IT-directed', reporter, gene, expression, was, activated, only, after, 'co-transfection', with, 'GATA-1,', implying, that, transcriptional, activation, of, 'GATA-1', in, the, testis, might, be, at, least, partially, mediated, through, these, 'GATA', regulatory, elements])]). relacion([sujeto(['We', also]), verbo([found]), complemento([that, the, endogenous, 'GATA-1', gene, was, silent, in, primary, culture, and, two, different, 'Sertoli', cell, 'lines,', and, that, the, repression, of, 'co-transfected', 'GATA-1', reporter, genes, could, not, be, relieved, by, forced, expression, of, 'GATA-1', in, 'Sertoli', cells])]). relacion([sujeto(['Thus', the, 'GATA-IT', promoter, may, be, under, the, control, of, a, regulatory, network, in, 'Sertoli', cells, which]), verbo([involves]), complemento([both, positive, and, negative, regulation, of, 'transcription,', and, conserved, 'GATA', motifs, found, in, the, 'IT', promoter, may, be, required, for, transducing, these, effects])]). relacion([sujeto(['We']), verbo([have]), complemento([set, out, to, test, a, model, for, 'tissue-specific', gene, expression, that, relies, on, the, early, replication, of, expressed, genes, to, sequester, limiting, activating, transcription, factors])]). relacion([sujeto(['Using', an, erythroid, cell, 'line,', we]), verbo([have]), complemento([tested, the, changes, in, the, 'DNA', binding, activity, of, the, 'lineage-restricted', transcription, factor, 'GATA-1', through, the, cell, cycle])]). relacion([sujeto(['We']), verbo([find]), complemento([that, 'GATA-1', activity, is, low, in, 'G1,', peaks, in, 'mid-S', 'phase,', and, then, decreases, in, 'G2/M'])]). relacion([sujeto(['In', 'contrast,', the]), verbo([binding]), complemento([activities, of, two, ubiquitous, transcription, 'factors,', 'Oct1', and, 'Sp1,', remain, high, in, 'G2/M'])]). relacion([sujeto(['GATA-1', protein, and, mRNA, vary, in, a, similar, manner, through, the, cell, 'cycle,']), verbo([suggesting]), complemento([that, the, expression, of, the, gene, or, the, stability, of, its, message, is, regulated])]). relacion([sujeto(['Although', a, number, of, transcription, factors]), verbo([involved]), complemento([in, the, control, of, the, cell, cycle, or, 'DNA', replication, have, been, shown, to, peak, in, 'S', 'phase,', this, is, the, first, example, of, a, 'lineage-restricted', transcription, factor, displaying, 'S', 'phase-specific', 'DNA', binding, activity])]). relacion([sujeto(['One', interpretation, of, these, data]), verbo([leads]), complemento([to, a, model, in, which, the, peak, in, 'GATA-1', 'DNA', binding, amplifies, the, effect, of, early, replication, on, the, activation, of, 'erythroid-specific', genes, at, the, same, time, as, preventing, activation, of, 'non-erythroid', genes, containing, 'GATA-responsive', elements])]). relacion([sujeto(['Through', the, ectopic, expression, of, receptor, mutants, in, lymphoid, and, myeloid, cell, 'lines,', insight]), verbo([has]), complemento([been, gained, regarding, effectors, that, regulate, 'Epo-induced', proliferation])]). relacion([sujeto(['In', 'contrast,', effectors, that]), verbo([regulate]), complemento(['Epo-induced', differentiation, events, '(', e])]). relacion([sujeto(['For', in, vitro, studies, of, this, 'pathway,', erythroleukemic, 'SKT6', cell, sublines]), verbo([have]), complemento([been, isolated, which, stably, and, efficiently, hemoglobinize, in, response, to, 'Epo'])]). relacion([sujeto(['Epo', rapidly]), verbo([activated]), complemento(['Jak2,', 'STAT5', and, detectably, 'STATs', 1, and, 3, ',', while, no, effects, on, 'GATA-1,', 'EKLF', or, 'STAT5', expression, were, observed])]). relacion([sujeto(['Finally,', efficient, hemoglobinization, of, 'SKT6', cells, was, shown, to, be]), verbo([mediated]), complemento([by, chimeric, receptors, comprised, of, the, 'EGF', receptor, extracellular, domain, and, truncated, cytoplasmic, subdomains, of, either, the, 'Epo', receptor, or, the, prolactin, 'Nb2', receptor])]). relacion([sujeto(['This', work, further, establishes, 'SKT6', cells, as, an, important, model, for, studies, of, 'Epo-stimulated', 'differentiation,', and, shows, that, this, signaling, pathway, is]), verbo([promoted]), complemento([by, a, limited, set, of, 'membrane-proximal', receptor, domains, and, effectors])]). relacion([sujeto(['During', 15, days, of, treatment, of, 'K562', cells, with, sodium, 'phenylacetate,', we, observed, an]), verbo([increase]), complemento([in, the, cellular, hemoglobin, concentration, with, a, similar, increase, in, the, expression, of, 'gamma-globin', mRNA])]). relacion([sujeto(['Likewise,', the, level, of, expression, of, the, erythroid, transcription, factors, 'GATA-1,', 'GATA-2,', 'NF-E2,', 'SCL', and, 'RBTN2,', all]), verbo([expressed]), complemento([in, untreated, 'K562', 'cells,', did, not, increase, during, sodium, phenylacetate, induced, erythroid, differentiation])]). relacion([sujeto(['The', expression, of, the]), verbo([nuclear]), complemento([factors, 'Evi-1', and, 'c-myb,', known, to, inhibit, erythroid, 'differentiation,', did, not, decrease])]). relacion([sujeto(['We', conclude, that, sodium, phenylacetate, treatment, of, 'K562', cells]), verbo([increases]), complemento(['gamma-globin', mRNA, and, induces, cell, maturation, as, judged, by, morphology, without, affecting, the, expression, of, the, erythroid, transcription, 'factors,', some, of, which, are, known, to, be, involved, in, the, regulation, of, 'beta-like', globin, genes])]). relacion([sujeto(['The', 'cells,', cultured, for, 1, week, in, the, peritoneal, cavity, of, syngenic, 'BDF1', 'mice,', proliferate, and]), verbo([express]), complemento([high, levels, of, 'L-histidine', decarboxylase, '(', 'HDC)', and, mouse, mast, cell, protease, '(', 'MMCP)-6', 'mRNAs,', indicating, the, ability, of, 'P815', cells, to, differentiate, toward, mature, connective, tissue, mast, cells])]). relacion([sujeto(['Peritoneal', fluid, aspirated, from, 'P815-inoculated', 'BDF1', mouse, and, added, to, cultured, 'P815', cells, in, vitro, was, also]), verbo([found]), complemento([to, induce, 'HDC', mRNA, 'expression,', suggesting, that, at, least, some, of, the, humoral, factors, in, the, peritoneal, fluid, induce, 'HDC', mRNA, transcription])]). relacion([sujeto(['Among', the, erythroid, transcription, 'factors,', 'P815', cells]), verbo([expressed]), complemento(['GATA-2', but, not, 'GATA-1', mRNA, before, and, after, the, intraperitoneal, incubation])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, 'NF-E2', is, also, an, important, transcription, factor, in, mast, cell, differentiation])]). relacion([sujeto(['Acute', megakaryoblastic, leukemia, '(', 'AML-M7)', and, transient, myeloproliferative, disorder, in, 'Down\'s', syndrome, '(', 'TMD)', are, characterized, by, rapid, growth, of, abnormal, blast, cells, which]), verbo([express]), complemento([megakaryocytic, markers])]). relacion([sujeto(['These', blast, cells]), verbo([express]), complemento(['lineage-specific', transcription, factors, such, as, 'GATA-1', common, to, these, lineages, and, frequently, express, 'erythroid-specific', mRNAs, such, as, 'gamma-globin', and, erythroid, 'delta-aminolevulinate', synthase, '(', 'ALAS-E),', indicating, that, most, of, the, blasts, in, 'M7', and, 'TMD', cases, have, erythroid, and, megakaryocytic, phenotypes])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, blasts, in, 'M7', and, 'TMD', may, correspond, to, progenitors, of, both, erythroid, and, megakaryocytic, lineages])]). relacion([sujeto(['Among', the, known, transcription, 'factors,', both, 'GATA-1', and, 'SCL', play, roles, in, the, cellular, differentiation, of, erythrocytic, and, megakaryocytic, 'lineages,', while, 'GATA-2', is, thought, to]), verbo([maintain]), complemento([and, promote, the, proliferation, of, early, hematopoietic, progenitors])]). relacion([sujeto(['AML', patients, with, both, 'GATA-1', and, 'SCL', expression]), verbo([have]), complemento([a, poor, prognosis, and, have, some, characteristic, clinical, and, hematologic, features])]). relacion([sujeto(['The', 'EVI1', gene, may, be]), verbo([expressed]), complemento([through, at, least, two, pathways, in, hematologic, 'malignancies;', one, is, related, to, chromosomal, changes, at, 3, 'q26,', while, the, other, is, related, to, myelodysplasia, regardless, of, chromosomal, changes, at, 3, q26, region])]). relacion([sujeto(['These', findings]), verbo([suggest]), complemento([that, the, pattern, of, expression, in, transcription, factors, in, abnormal, hematopoietic, cells, is, reflected, in, the, malignant, phenotype, and, play, a, role, in, the, pathogenesis, of, the, disease])]). relacion([sujeto(['Much', of, our, understanding, of, the, process, by, which, enhancers]), verbo([activate]), complemento([transcription, has, been, gained, from, 'transient-transfection', studies, in, which, the, 'DNA', is, not, assembled, with, histones, and, other, chromatin, proteins, as, it, is, in, the, cell, nucleus])]). relacion([sujeto(['The', minichromosomes, replicate, and, are]), verbo([maintained]), complemento([at, stable, copy, number, in, human, erythroid, cells])]). relacion([sujeto(['Expression', of, the, minichromosomal, 'epsilon-globin', gene]), verbo([requires]), complemento([the, presence, of, 'beta-globin', 'LCR', elements, in, 'cis,', as, is, the, case, for, the, chromosomal, gene])]). relacion([sujeto(['In', minichromosomes, with, a, '(', 'mu)LCR', or, 'DNase', 'I-hypersensitive', site, 2, '(', 'HS2)', which, actively]), verbo([transcribe]), complemento([the, 'epsilon-globin', 'gene,', the, nucleosome, at, the, promoter, is, altered, or, disrupted, while, positioning, of, nucleosomes, in, the, rest, of, the, locus, is, retained])]). relacion([sujeto(['Transcriptional', activation, and, promoter, 'remodeling,', as, well, as, formation, of, the, 'HS2', structure, 'itself,', depended, on, the, presence, of, the, 'NF-E2']), verbo([binding]), complemento([motif, in, 'HS2'])]). relacion([sujeto(['The', simple, availability, of, erythroid, transcription, factors, that]), verbo([recognize]), complemento([these, motifs, is, insufficient, to, allow, expression])]). relacion([sujeto(['These', observations, are, consistent, with, the, idea, that, one, role, of, the, 'beta-globin', 'LCR', is, to]), verbo([maintain]), complemento([promoters, free, of, nucleosomes])]). relacion([sujeto(['The', restricted, structural, change, observed, upon, transcriptional, activation, may, indicate, that, the, 'LCR', need, only, make, a, specific, contact, with, the, proximal, gene, promoter, to]), verbo([activate]), complemento([transcription])]). relacion([sujeto(['The', 'X', 'chromosome-linked', transcription, factor, 'GATA-1', is]), verbo([expressed]), complemento([specifically, in, 'erythroid,', 'mast,', 'megakaryocyte,', and, eosinophil, 'lineages,', as, well, as, in, hematopoietic, progenitors])]). relacion([sujeto(['Prior', studies, revealed, that, 'gene-disrupted', 'GATA-1-', embryonic, stem, cells, give, rise, to, adult, '(', or, 'definitive)', erythroid, precursors]), verbo([arrested]), complemento([at, the, proerythroblast, stage, in, vitro, and, fail, to, contribute, to, adult, red, blood, cells, in, chimeric, mice, but, did, not, clarify, a, role, in, embryonic, '(', or, yolk, sac, 'derived)', erythroid, cells])]). relacion([sujeto(['To', examine, the, consequences, of, 'GATA-1']), verbo([loss]), complemento([on, embryonic, erythropoiesis, in, 'vivo,', we, inactivated, the, 'GATA-1', locus, in, embryonic, stem, cells, by, gene, targeting, and, transmitted, the, mutated, allele, through, the, mouse, germ, line])]). relacion([sujeto([5, ',', 'GATA-1-', embryos, exhibit, extreme, pallor, yet, contain, embryonic, erythroid, cells]), verbo([arrested]), complemento([at, an, early, 'proerythroblast-like', stage, of, their, development])]). relacion([sujeto(['Embryos', stain, weakly, with, benzidine, 'reagent,', and, yolk, sac, cells]), verbo([express]), complemento([globin, 'RNAs,', indicating, globin, gene, activation, in, the, absence, of, 'GATA-1'])]). relacion([sujeto(['However,', these, mice, recover, during, the, neonatal, 'period,', presumably, as, a, result, of, in, vivo, selection, for, progenitors, able, to]), verbo([express]), complemento(['GATA-1'])]). relacion([sujeto(['Moreover,', the, recovery, of, 'GATA-1+/-', mice, from, anemia, seen, at, birth]), verbo([provides]), complemento([evidence, indicating, a, role, for, 'GATA-1', at, the, hematopoietic, progenitor, cell, level])]). relacion([sujeto(['The', 'X-linked', mouse, mutant, 'phenotype,', tattered, '(', 'Td),', is]), verbo([associated]), complemento([with, prenatal, lethality, of, males, and, has, been, mapped, previously, to, the, proximal, region, of, the, mouse, 'X', chromosome])]). relacion([sujeto(['We']), verbo([report]), complemento([here, a, refined, position, for, 'Td', and, demonstrate, that, it, lies, in, the, approximately, 0.9, -, cM, interval, between, 'DXMit55', and, 'Xkh'])]). relacion([sujeto(['Histological', analysis, of, dorsal, skin, taken, from, 5, -, 'day-old', heterozygous, animals, revealed, that, the, mutation, was]), verbo([associated]), complemento([with, patches, of, hyperkeratinzation, in, the, epidermis, and, in, the, hair, 'follicles,', accompanied, by, a, mild, inflammatory, infiltrate, in, the, underlying, dermis])]). relacion([sujeto(['To', determine, if, recombinant, human, '(', 'rh)', 'TPO']), verbo([has]), complemento(['proliferation-supporting', and, 'differentiation-inducing', activities, in, 'AML', 'cells,', 15, cases, of, 'AML', cells, that, were, exclusively, composed, of, undifferentiated, leukemia, cells, and, showed, growth, response, to, rhTPO, in, a, 'short-term', culture, '(', 72, 'hours)', were, subjected, to, 'long-term', suspension, culture, with, or, without, rhTPO])]). relacion([sujeto(['In', addition, to, the, 'proliferation-supporting', 'activity,', rhTPO, was]), verbo([found]), complemento([to, induce, 'AML', cells, to, progress, to, some, degree, of, megakaryocytic, differentiation, at, both, morphologic, and, 'surface-phenotypic', level, in, 2, 'AML', cases, with, 'M0', and, 'M7', subtypes])]). relacion([sujeto(['By', 'contrast,', the, expression, of, 'erythroid/megakaryocyte-specific', transcription, factors, '(', 'GATA-1,', 'GATA-2,', and, 'NF-E2)', was, markedly]), verbo([induced]), complemento([or, enhanced, in, only, 2, 'AML', cases, that, showed, megakaryocytic, differentiation, in, response, to, rhTPO])]). relacion([sujeto(['These', results]), verbo([suggested]), complemento(['that,', at, least, in, a, fraction, of, 'AML', 'cases,', 'TPO', could, not, only, support, the, proliferation, of, 'AML', cells, irrespective, of, 'AML', 'subtypes,', but, could, also, induce, megakaryocytic, 'differentiation,', possibly, through, activation, of, 'GATA-1,', 'GATA-2,', and, 'NF-E2'])]). relacion([sujeto(['DNase', 'I', hypersensitive, sites, are, thought, to, represent, 'nucleosome-free', regions, of, 'DNA', which, are]), verbo([bound]), complemento([by, 'trans-acting', factors])]). relacion([sujeto(['Of', the, four, hypersensitive, sites, only, 'HS2']), verbo([acts]), complemento([as, a, transcriptional, enhancer])]). relacion([sujeto(['In', this, 'study,', we, examine, the]), verbo([binding]), complemento([of, an, erythroid, protein, to, its, site, within, 'HS2', in, chromatin, in, vitro])]). relacion([sujeto(['NF-E2']), verbo([binds]), complemento([two, tandem, 'AP1-like', sites, in, 'HS2', which, form, the, core, of, its, enhancer, activity])]). relacion([sujeto(['In', this, 'study,', we, show, that, when]), verbo([bound]), complemento([to, in, 'vitro-reconstituted', 'chromatin,', 'NF-E2', forms, a, 'DNase', 'I', hypersensitive, site, at, 'HS2', similar, to, the, site, observed, in, vivo])]). relacion([sujeto(['Moreover,', 'NF-E2']), verbo([binding]), complemento([in, vitro, results, in, a, disruption, of, nucleosome, structure, which, can, be, detected, 200, bp, away])]). relacion([sujeto(['Interestingly,', the, hematopoietic, 'cell-specific', 'subunit,', 'p45,', is, necessary, for]), verbo([binding]), complemento([to, chromatin, but, not, to, naked, 'DNA'])]). relacion([sujeto(['Interaction', of, 'NF-E2', with, its, site, in, 'chromatin-reconstituted', 'HS2', allows, a, second, erythroid, 'factor,', 'GATA-1,', to]), verbo([bind]), complemento([its, nearby, sites])]). relacion([sujeto(['Lastly,', nucleosome, disruption, by, 'NF-E2', is, an, 'ATP-dependent', 'process,']), verbo([suggesting]), complemento([the, involvement, of, 'energy-dependent', nucleosome, remodeling, factors])]). relacion([sujeto(['Bernard-Soulier', 'Syndrome', '(', 'BSS)', is, a, rare, congenital, bleeding, disorder, due, to, absent, or]), verbo([decreased]), complemento([expression, of, the, glycoprotein, 'Ib-IX-V', '(', 'GpIb-IX-V)', receptor, complex, on, the, platelet, surface])]). relacion([sujeto(['To', 'date,', only, mutations, in, 'GpIbalpha', or, 'GpIX']), verbo([have]), complemento([been, reported, in, patients, with, 'BSS'])]). relacion([sujeto(['GpIbbeta', differs, from, the, other, proteins, in, this, receptor, in, that, the, gene, is, more, 'complex,', and, an, alternative, form, is]), verbo([expressed]), complemento([in, cells, of, 'non-megakaryocytic', 'lineage,', including, endothelial, cells])]). relacion([sujeto(['It', appears, that, the, megakaryocytic, and, endothelial, cell, mRNA, species, are]), verbo([transcribed]), complemento([from, different, start, sites, and, have, different, proximal, promoter, regions])]). relacion([sujeto(['We']), verbo([have]), complemento([identified, a, patient, with, 'BSS', who, has, a, deletion, on, one, chromosome, 22, ',', resulting, in, velocardiofacial, syndrome])]). relacion([sujeto(['The', 'GpIbbeta', gene]), verbo([has]), complemento([been, mapped, to, this, deleted, '(', 22, q11])]). relacion([sujeto(['The', patient]), verbo([has]), complemento([greatly, reduced, levels, of, 'GpIbbeta', mRNA, and, no, detectable, platelet, 'GpIbbeta', 'protein,', suggesting, that, his, 'BSS', results, from, a, mutation, in, his, remaining, 'GpIbbeta', allele])]). relacion([sujeto(['The', mutation, changes, a, 'GATA', consensus]), verbo([binding]), complemento(['site,', disrupts, 'GATA-1', binding, to, the, mutated, 'site,', and, decreases, promoter, activity, by, 84, '%'])]). relacion([sujeto(['Thus,', in, this, 'patient,', 'Bernard-Soulier', syndrome, results, from, a, deletion, of, one, copy, of, 'GpIbbeta', and, a, mutated, 'GATA']), verbo([binding]), complemento([site, in, the, promoter, of, the, remaining, 'allele,', resulting, in, decreased, promoter, function, and, 'GpIbbeta', gene, transcription])]). relacion([sujeto(['The', 'myb-ets-containing', 'ME26', virus]), verbo([causes]), complemento([erythroleukemia, in, mice, by, a, novel, mechanism, involving, the, inappropriate, activation, of, 'erythroid-specific', genes, in, hematopoietic, precursor, cells])]). relacion([sujeto(['We']), verbo([have]), complemento([previously, shown, that, the, 'ME26', viral, protein, can, transactivate, the, 'GATA-1', promoter, in, transient, transactivation, assays, carried, out, in, mouse, fibroblasts])]). relacion([sujeto(['The', mouse, 'GATA-1', 'promoter,', whose, activity, is]), verbo([regulated]), complemento([by, the, 'GATA-1', protein, 'itself,', contains, a, double, 'GATA', consensus, sequence, at, its, 5, '\'', end, and, two, 'CACCC', elements, at, its, 3, '\'', 'end,', both, of, which, are, crucial, for, promoter, activity, in, erythroid, 'cells,', as, well, as, a, nonconsensus, 'GATA', sequence, and, several, putative, 'c-myb', and, 'c-ets', binding, sites])]). relacion([sujeto(['In', order, to, determine, which, sequences, in, the, 'GATA-1', promoter, are, crucial, for, activation, by, the, 'ME26', viral, 'protein,', we, made, deletions, of, the, 'promoter,', cloned, them, into, a, luciferase, expression, vector, and, tested, their, activity, in, mouse, 'fibroblasts,', which, do, not]), verbo([express]), complemento(['GATA-1'])]). relacion([sujeto(['However,', we, could, detect, the, ubiquitous, transcription, factor, 'Sp1']), verbo([bound]), complemento([to, this, sequence])]). relacion([sujeto(['These', data, demonstrate, that, the, 'CACCC', element, is, necessary, for, 'GATA-1', promoter, transactivation, by, 'ME26', virus, and, that, the, viral, protein, may, indirectly, transactivate, the, promoter, by]), verbo([binding]), complemento([to, 'Sp1'])]). relacion([sujeto(['In', an, effort, to, understand, how, the, heme, biosynthetic, pathway, is, uniquely]), verbo([regulated]), complemento([in, erythroid, 'cells,', we, examined, the, structure, of, the, gene, encoding, murine, 'delta-aminolevulinate', dehydratase, '(', 'ALAD;', 'EC4'])]). relacion([sujeto(['Each', first, exon]), verbo([has]), complemento([its, own, promoter])]). relacion([sujeto(['In', 'contrast,', the, exon, 1, 'B', promoter, bears, regulatory, sequences, similar, to, those]), verbo([found]), complemento([for, 'beta-globin', and, other, 'erythroid-specific', genes])]). relacion([sujeto(['Tissue', distribution, studies]), verbo([reveal]), complemento([that, 'ALAD', mRNA, containing, axon, 1, 'A', is, 'ubiquitous,', whereas, mRNA, containing, axon, 1, 'B', is, found, only, in, erythroid, tissues])]). relacion([sujeto(['This', 'finding,', together, with, our, further, observation, that, 'GATA-1', mRNA, levels]), verbo([increase]), complemento([3, -, fold, during, maturation, of, murine, erythroid, progenitor, 'cells,', may, help, explain, simultaneous, 3, -, fold, increases, in, exon, 1, 'B', expression])]). relacion([sujeto(['The', unexpected, result, that, axon, 1, 'A', expression, also]), verbo([increases]), complemento([3, -, fold, during, 'CFU-E', maturation, may, be, attributable, to, the, action, of, 'NF-E2,', since, there, is, a, potential, binding, site, in, a, position, analogous, to, the, 'NF-E2', site, in, the, locus, control, region, of, the, 'beta-globin', gene, cluster])]). relacion([sujeto(['We', quantitated, 'WT1', expression, levels, in, 62, acute, myelogenous, leukemia, '(', 'AML)', samples, and]), verbo([found]), complemento([that, 82, '%', strongly, expressed, 'WT1'])]). relacion([sujeto(['WT1', was, strongly]), verbo([expressed]), complemento([in, normal, 'CD34+', bone, marrow, '(', 'BM)', stem, cells, but, only, weakly, or, not, expressed, in, normal, mature, blood, cells])]). relacion([sujeto(['This']), verbo([suggests]), complemento([that, 'WT1', gene, expression, is, associated, with, immature, 'cells,', which, have, high, proliferative, capacities])]). relacion([sujeto(['Previous', studies, of, 'WT1', gene, regulation, showed, that, 'GATA-1', may]), verbo([regulate]), complemento(['WT1', expression])]). relacion([sujeto(['Overall,', 'AML', samples]), verbo([expressed]), complemento([significant, amounts, of, both, 'WT1', and, 'GATA-1'])]). relacion([sujeto(['However,', 'AML', samples, with, 16, q22, 'abnormalities,', presumably, interrupting, the, core]), verbo([binding]), complemento([factor, '(', 'CBF)', beta, gene, expressed, lower, than, normal, levels, of, 'GATA-1', but, high, levels, of, 'WT1'])]). relacion([sujeto(['Our', data]), verbo([suggest]), complemento([that, the, transcription, factor, 'CBF', beta, may, be, important, for, 'GATA-1', gene, regulation])]). relacion([sujeto(['Previous', comparisons, of, gene, location, in, the, three, major, groups, of, mammals, '(', 'eutherians,', 'marsupials,', and, 'monotremes)']), verbo([have]), complemento([suggested, that, the, long, arm, of, the, human, 'X', represents, the, ancestral, mammalian, 'X', 'chromosome,', whereas, the, short, arm, represents, an, autosomal, 'region(s)', recently, added, to, the, eutherian, 'X', chromosome])]). relacion([sujeto(['To', identify, the, fusion, point, of, this, ancient, 'X-autosome', 'rearrangement,', we]), verbo([have]), complemento([mapped, four, 'genes,', three, of, which, map, near, the, centromere, of, the, human, 'Xp,', in, marsupials, and, in, a, monotreme])]). relacion([sujeto(['We']), verbo([found]), complemento([that, 'ARAF1,', 'ALAS2,', and, 'GATA1', are, located, on, the, 'X', chromosome, in, 'marsupials,', and, 'ALAS2', and, 'GATA1', are, also, located, on, the, 'X', in, the, platypus])]). relacion([sujeto(['The', fusion, point, between, the]), verbo([conserved]), complemento([region, and, the, recently, added, regions, therefore, maps, to, human, 'Xp11'])]). relacion([sujeto([23, ',', although, gene, order, on, the, human, 'X', indicates, that, there]), verbo([has]), complemento([been, some, rearrangement, of, this, region])]). relacion([sujeto(['To', characterize, the, 'protein-DNA', interactions, important, for, the, developmental, control, of, the, human, 'beta-globin', 'locus,', we, analyzed, by, in, vivo, dimethyl, sulfate, footprinting, erythroid, cells]), verbo([expressing]), complemento([either, the, fetal, or, the, adult, globin, developmental, program])]). relacion([sujeto(['In', 'contrast,', in, vivo, footprints, on, 'GT', '(', 'CACCC)', motifs, differed, between, the, cells]), verbo([expressing]), complemento([the, fetal, or, the, adult, globin, program])]). relacion([sujeto(['In', promoter, 'regions,', the, actively]), verbo([transcribed]), complemento([genes, demonstrated, extensive, and, consistent, footprints, over, the, canonical, 'elements,', such, as, 'CACCC', and, 'CCAAT', motifs])]). relacion([sujeto(['The', adult, globin]), verbo([expressing]), complemento([cells, displayed, more, extensive, footprints, than, the, fetal, globin, expressing, cells, in, the, 3, '\'', regulatory, sequences, of, both, the, 'Agamma-', and, the, 'beta-globin', 'genes,', suggesting, a, role, of, these, 3, '\'', elements, in, 'beta-globin', gene, expression])]). relacion([sujeto(['Our', results]), verbo([suggest]), complemento([that, the, bulk, of, 'protein-DNA', interactions, that, underlies, the, developmental, control, of, globin, genes, takes, place, in, the, 'gamma-', and, 'beta-globin', gene, 'promoters,', and, that, 'GT', motifs, of, the, 'beta-globin', locus, 'LCR', may, play, a, role, in, the, developmental, regulation, of, human, 'beta-globin', gene, 'expression,', perhaps, by, increasing, the, probability, of, interaction, of, the, 'LCR', holocomplex, with, the, fetal, or, the, adult, globin, gene])]). relacion([sujeto(['The', far, upstream, region, '(', -, 1.2, -, 0.9, kilobase, 'pairs)', of, the, mouse, glycophorin, gene, contains, the, locus, control, region, '(', 'LCR)-like', 'region,', which]), verbo([acts]), complemento([as, an, 'erythroid-specific', enhancer, dependent, on, chromosomal, integration, in, murine, erythroleukemia, '(', 'MEL)', cells])]). relacion([sujeto(['In', the, present, 'study,', we, demonstrated, that, this, region]), verbo([binds]), complemento([six, nuclear, factors])]). relacion([sujeto(['The']), verbo([binding]), complemento([of, 'GATA-1', to, corresponding, sites, did, not, show, any, change, before, or, after, induction, with, dimethyl, 'sulfoxide,', but, the, binding, of, 'Spi-1/PU'])]). relacion([sujeto([l, and, an, unidentified, factor, called, glycophorin, regulatory, element]), verbo([binding]), complemento([factor, '(', 'GRBF)', showed, a, change, during, induction])]). relacion([sujeto(['While']), verbo([binding]), complemento([activity, of, 'Spi-l/PU'])]). relacion([sujeto([l, dropped, soon, after, 'induction,', the, 'GRBF', activity]), verbo([increased]), complemento([after, induction, when, expression, of, the, glycophorin, gene, began])]). relacion([sujeto(['After', identification, of, the, consensus]), verbo([binding]), complemento([site, of, 'GRBF,', we, cloned, cDNA, for, that, factor, by, 'Southwestern', 'method,', and, it, was, identified, as, a, previously, reported, transcription, 'factor,', 'delta,', a, murine, form, of, 'YY-l', which, is, a, versatile, transcription, factor])]). relacion([sujeto(['Mutation', analysis, in, the, 'delta/YY-1']), verbo([binding]), complemento([site, within, the, 'LCR-like', region, indicated, that, 'delta/YY-1', acts, as, a, regulatory, protein, in, combination, with, the, 'E-box-binding', protein, that, binds, to, the, neighboring, sequence])]). relacion([sujeto(['This', fragment, can]), verbo([bind]), complemento([several, 'trans-acting', factors, in, 'vitro,', including, 'GATA-1', and, members, of, the, 'Ets', family])]). relacion([sujeto(['GATA-1']), verbo([binds]), complemento([with, low, affinity, to, a, unique, 'GATA', motif, at, -, 70, in, the, 'MPL', 'promoter,', and, destruction, of, this, site, yields, only, a, modest, decrease, in, expression, level, in, 'HEL', cells])]). relacion([sujeto(['Ets', proteins, also]), verbo([bind]), complemento([with, low, affinity, to, two, sites])]). relacion([sujeto(['We']), verbo([found]), complemento([that, 'UT-7/GM,', which, is, a, subline, of, 'UT-7,', but, neither, 'UT-7', nor, 'UT-7/EPO,', can, proliferate, in, response, to, 'TPO'])]). relacion([sujeto(['UT-7/TPO', can, be]), verbo([maintained]), complemento([by, 'TPO', 'alone,', with, a, doubling, time, of, 24, hours, in, log, growth, phase])]). relacion([sujeto(['Thus,', 'UT-7/TPO']), verbo([has]), complemento([an, absolute, dependence, on, 'TPO', for, growth, and, survival, and, has, mature, megakaryocytic, features])]). relacion([sujeto(['The', mRNA, level, of, 'NF-', 'E2', 'p45,']), verbo([reported]), complemento([to, be, an, 'erythroid-specific', transcription, 'factor,', was, upregulated, in, 'UT-7/TPO,', whereas, it, was, 'down-regulated', in, the, erythroid, 'subline,', 'UT-7/EPO'])]). relacion([sujeto(['Not', only, 'EPO', but, also, 'TPO']), verbo([induced]), complemento([the, tyrosine, phosphorylation, of, 'JAK2', tyrosine, kinase, and, 'STAT5-related', protein])]). relacion([sujeto(['A', comprehensive, physical, contig, of, yeast, artificial, chromosomes, '(', 'YACs)', and, cosmid, clones, between, 'ZNF21', and, 'DXS255']), verbo([has]), complemento([been, 'constructed,', spanning, 2, 'Mb', within, the, region, 'Xp11'])]). relacion([sujeto(['As', a, portion, of, the, region, was]), verbo([found]), complemento([to, be, particularly, unstable, in, 'yeast,', the, integrity, of, the, contig, is, dependent, on, additional, information, provided, by, the, 'sequence-tagged', site, '(', 'STS)', content, of, cosmid, clones, and, 'DNA', marker, retention, in, conventional, and, radiation, hybrids])]). relacion([sujeto(['The', relative, order, of, previously, known, genes, and]), verbo([expressed]), complemento([sequence, tags, in, this, region, is, predicted, to, be, 'Xpter-ZNF21-DXS7465E', '(', 'MG66)-DXS7927E', '(', 'MG81)-WASP,', 'DXS1011E,', 'DXS7467E', '(', 'MG21)-DXS-', '7466E', '(', 'MG44)-GATA1-DXS7469E', '(', 'Xp664)-TFE3-SYP', '(', 'DXS1007E)-Xcen'])]). relacion([sujeto(['This', contig, extends, the, coverage, in, 'Xp11', and]), verbo([provides]), complemento([a, framework, for, the, future, identification, and, mapping, of, new, 'genes,', as, well, as, the, resources, for, developing, 'DNA', sequencing, templates])]). relacion([sujeto(['GATA-1,', a, transcription, factor, essential, for, the, development, of, the, erythroid, 'lineage,', contains, two, adjacent, highly]), verbo([conserved]), complemento([zinc, finger, motifs])]). relacion([sujeto(['The', 'carboxy-terminal', finger, is, necessary, and, sufficient, for, specific]), verbo([binding]), complemento([to, the, consensus, 'GATA', recognition, 'sequence:', mutant, proteins, containing, only, the, 'amino-terminal', finger, do, not, bind])]). relacion([sujeto(['The', site, occurs, in, the, 'GATA-1', gene, promoters, of, 'chickens,', 'mice,', and, humans, but, occurs, very, infrequently, in, other, vertebrate, genes, known, to, be]), verbo([regulated]), complemento([by, 'GATA', proteins])]). relacion([sujeto(['GATA-1,', mainly]), verbo([expressed]), complemento([during, erythroid, 'differentiation,', has, been, shown, to, regulate, the, genes, specifically, expressed, in, the, late, stages, of, erythropoiesis, and, to, protect, erythroid, cells, from, 'apoptosis,', suggesting, that, it, might, interfere, with, the, cell, cycle])]). relacion([sujeto(['By']), verbo([expressing]), complemento([the, retrovirally, transduced, human, 'GATA-1', cDNA, in, 'NIH3T3', 'fibroblasts,', we, have, shown, that, 'GATA-1', alone, was, unable, to, transactivate, its, 'erythroid-specific', target, genes, in, these, nonerythroid, cells])]). relacion([sujeto(['The', cloning, efficiency, of, the, 'GATA-1-expressing', fibroblasts, was]), verbo([maintained]), complemento([but, their, 'S', phase, was, greatly, elongated, and, their, 'G1', and, 'G2/M', phases, were, 'reduced,', impairing, substantially, their, proliferation])]). relacion([sujeto(['GATA-1-expressing', fibroblasts]), verbo([expressed]), complemento(['D1,', 'A,', and, 'B1', cyclin, mRNAs, under, conditions, of, serum, starvation, or, at, 'confluence,', whereas, these, cyclin, mRNAs, were, downregulated, in, the, parental, 'NIH3T3', cells, cultured, under, the, same, conditions])]). relacion([sujeto(['Steroid', hormones]), verbo([regulate]), complemento([diverse, biological, 'functions,', including, programmed, cell, death, '(', 'apoptosis)'])]). relacion([sujeto(['Although', steroid, receptors]), verbo([have]), complemento([been, studied, 'extensively,', relatively, little, is, known, regarding, the, cellular, targets, through, which, apoptosis, is, triggered])]). relacion([sujeto(['We', show, here, that, the, 'ligand-activated', estrogen, receptor, '(', 'ER)']), verbo([induces]), complemento([apoptosis, in, an, erythroid, cell, line, by, binding, 'to,', and, consequently, inhibiting, the, activity, 'of,', 'GATA-1,', an, erythroid, transcription, factor, essential, for, the, survival, and, maturation, of, erythroid, precursor, cells])]). relacion([sujeto(['GATA-1', inhibition, is, reflected, in, the, downregulation, of, presumptive, 'GATA-1']), verbo([target]), complemento([genes])]). relacion([sujeto(['Induction', of, apoptosis, by, a, mutant, 'ER', defective, in]), verbo([binding]), complemento([to, the, estrogen, response, element, but, active, in, 'GATA-1', inhibition, suggests, that, 'ER-mediated', inhibition, of, 'GATA-1', is, direct, and, does, not, require, estrogen, response, 'element-dependent', transcriptional, activation])]). relacion([sujeto(['Thus,', a, 'lineage-restricted', transcription, 'factor,', such, as, 'GATA-1,', constitutes, one, cellular]), verbo([target]), complemento([through, which, steroid, hormones, may, control, apoptosis])]). relacion([sujeto(['Human', erythroleukemic, 'K', 562, cells, were]), verbo([induced]), complemento([to, were, induced, to, differentiate, along, the, erythroid, lineage, by, anthracycline, antitumor, 'drugs,', such, as, aclacinomycin, '(', 'ACLA)', and, doxorubicin, '(', 'DOX)'])]). relacion([sujeto(['Subsequent', stimulation, of, heme, and, globin, synthesis]), verbo([led]), complemento([to, a, differential, quantitative, expression, of, hemoglobins])]). relacion([sujeto(['Although', 'ACLA', and, 'DOX']), verbo([increased]), complemento([both, the, expression, of, 'gamma-globin', and, porphobilinogen, deaminase, 'mRNAs,', striking, differences, were, observed, in, the, expression, of, erythropoietin, receptor, mRNAs, and, in, erythroid, transcription, factors, 'GATA-1', and, 'NF-E2,', known, to, play, a, key, role, in, erythroid, gene, regulation])]). relacion([sujeto(['Indeed,', 'ACLA']), verbo([induces]), complemento([an, increase, either, in, the, binding, capacity, of, 'GATA-1', and, 'NF-E2', or, in, the, accumulation, of, erythropoietin, 'receptor,', 'GATA-1', and, 'NF-E2', transcripts])]). relacion([sujeto(['In', 'contrast,', their, expression, with, 'DOX', was, not, significantly, modified, compared, to, uninduced, 'cells,', except, for, a, slight]), verbo([decrease]), complemento([in, 'NF-E2', expression, on, day, 3])]). relacion([sujeto([increased, expression, of, erythroid, transcription, factors, and, erythroid, genes, are]), verbo([associated]), complemento([only, with, 'ACLA', 'treatment,', and, 2])]). relacion([sujeto([although, cytotoxicity, of, both, 'ACLA', and, 'DOX', is, certainly, dependent, on, 'DNA', 'intercalation,', regulation, of, differentiation, processes, by, these, two, drugs]), verbo([involves]), complemento([distinct, mechanisms])]). relacion([sujeto(['To']), verbo([provide]), complemento([insight, into, the, mechanisms, by, which, 'c-myb', regulates, 'hematopoiesis,', we, analyzed, the, expression, of, markers, for, multiple, hematopoietic, lineages, in, differentiating, parental, embryonic, stem, '(', 'ES)', cells, and, in, 'ES', cells, transfected, with, 'c-myb', or, with, a, mutant, 'c-myb', deficient, in, 'DNA', binding, and, assessed, the, ability, of, these, cells, to, undergo, hematopoietic, commitment, and, colony, formation])]). relacion([sujeto(['Undifferentiated', 'ES', cells, transfected, with, intact, 'c-myb,', but, not, cells, transfected, with, mutant, 'c-myb,']), verbo([expressed]), complemento(['CD34,', 'c-kit,', 'GATA1,', and, flt3, mRNA, as, well, as, surface, 'CD34,', 'c-kit,', and, flt3, product])]). relacion([sujeto(['Transient', expression, assays]), verbo([suggested]), complemento([transactivation, of, gene, expression, dependent, on, interaction, with, 'Myb', binding, sites, in, the, 'CD34', and, 'GATA1', 5, '\'', flanking, regions])]). relacion([sujeto(['Colony', formation, was]), verbo([suppressed]), complemento([by, treatment, with, antisense, oligodeoxynucleotides, specifically, downregulating, 'c-kit', and, 'flt-3', expression])]). relacion([sujeto(['These', findings, indicate, that, 'c-myb']), verbo([regulates]), complemento([hematopoietic, commitment, and, progenitor, cell, proliferation, and, differentiation, through, the, activation, of, certain, genes, that, define, the, 'stem/progenitor', cell, compartment])]). relacion([sujeto(['Using', 'Drosophila', 'S2', 'cells,', the, actions, of, 'GATA1,', 'Sp1,', and, erythroid, 'Kruppel-like', factor, '(', 'EKLF)', at, these, elements, within, model, erythroid, promoters]), verbo([have]), complemento([been, assessed])]). relacion([sujeto(['For', each, promoter, studied, '(', erythroid, pyruvate, 'kinase,', glycophorin, 'B,', and, a, murine, betamaj, 'globin-derived', 'construct,', 'GCT)', 'Sp1', and, 'EKLF', each]), verbo([activated]), complemento([transcription, despite, differences, in, 'CACC', element, 'sequence,', 'orientation,', and, positioning])]). relacion([sujeto(['However,', 'GATA1']), verbo([acted]), complemento([in, apparent, cooperativity, with, 'Sp1', at, the, pyruvate, kinase, 'promoter;', with, 'EKLF', at, the, betamaj, 'globin-derived', 'GCT', 'promoter;', and, with, either, 'Sp1', or, 'EKLF', at, the, glycophorin, 'B', promoter])]). relacion([sujeto(['Thus,', 'GATA1', may, functionally]), verbo([interact]), complemento([with, each, of, these, 'Krüppel-like', factors, depending, on, promoter, 'context;', and, at, the, 'GCT', 'promoter,', transcriptional, activation, by, 'GATA1', and, 'EKLF', was, &, 'gt;', or, =, 10, -, fold, higher, than, levels, attributable, to, additive, effects])]). relacion([sujeto(['The', possibility, that, interactions, between, these, activators, may, be, direct, was, supported, by, the, specific]), verbo([binding]), complemento([of, 'baculoviral-expressed', 'EKLF', to, 'GATA1'])]). relacion([sujeto(['This']), verbo([report]), complemento([underlines, the, likelihood, that, discrete, roles, exist, for, 'Sp1', and, 'EKLF', in, erythroid, gene, 'activation,', and, supports, a, mechanism, of, direct, cooperativity, for, 'EKLF', and, 'GATA1', as, coregulators])]). relacion([sujeto(['For', 'example,', a, transfected, 'beta-globin', gene, is]), verbo([expressed]), complemento([in, an, inducible, manner, in, mouse, erythroleukemia, '(', 'MEL)', cells, while, a, transfected, 'alpha-globin', gene, is, constitutively, expressed, at, a, high, level, in, induced, and, uninduced, 'MEL', cells])]). relacion([sujeto(['Interestingly,', when, the, 'alpha-globin', gene, is, transferred, into, 'MEL', cells, as, part, of, human, chromosome, 16, ',', it, is, appropriately]), verbo([expressed]), complemento([in, an, inducible, manner])]). relacion([sujeto(['The', addition, of, each, of, these]), verbo([binding]), complemento([sites, to, the, 'alpha-globin', promoter, separately, did, not, result, in, inducibility, in, 'MEL', cells])]). relacion([sujeto(['This']), verbo([suggests]), complemento([that, erythroid, 'non-responsiveness', of, the, 'alpha-globin', gene, results, from, the, lack, of, erythroid, binding, sites, and, is, not, necessarily, a, function, of, the, constitutively, 'active,', 'GC', rich, promoter])]). relacion([sujeto(['Two', regions, are, hypersensitive, to, 'DNase', 'I', in, nuclei, of, cells, that]), verbo([express]), complemento(['MPL:', the, promoter, and, a, portion, of, intron, 6])]). relacion([sujeto(['This', fragment, can]), verbo([bind]), complemento([several, transacting, factors, in, 'vitro,', including, 'GATA-1', and, members, of, the, 'Ets', family])]). relacion([sujeto(['GATA-1']), verbo([binds]), complemento([with, low, affinity, to, a, unique, 'GATA', motif, at, -, 70, in, the, 'MPL', 'promoter,', and, destruction, of, this, site, yields, only, a, modest, decrease, in, expression, level, in, human, erythroleukemia, '(', 'HEL)', cells])]). relacion([sujeto(['Ets', proteins, also]), verbo([bind]), complemento([with, low, affinity, to, two, sites])]). relacion([sujeto(['Finally,', we, describe, other]), verbo([nuclear]), complemento([factor, binding, sites, that, may, be, involved, in, the, 'cell-type-specific', expression, of, 'MPL'])]). relacion([sujeto(['Low-density', marrow, cells, which]), verbo([bind]), complemento([to, wheat, germ, 'agglutinin,', but, not, to, the, antibody, 15.1])]). relacion([sujeto([1, ',', and, which, either, do, or, do, not]), verbo([retain]), complemento([the, dye, 'rhodamine-123', '(', 'Rho-bright', and, 'Rho-dull,', 'respectively),', were, purified])]). relacion([sujeto(['Multilineage,', 'erythroid-restricted', or, 'myeloid-restricted', differentiation, is, observed, when, the, cultures, are]), verbo([stimulated]), complemento([with, stem, cell, factor, '(', 'SCF)', +, interleukin, '(', 'IL)-3,', 'SCF', +, 'IL-3', +, 'Epo,', or, 'SCF', +, 'IL-3', +, 'granulocyte-colony-stimulating', 'factor,', respectively])]). relacion([sujeto(['Rho-dull', cells]), verbo([have]), complemento([barely, detectable, reconstitution, potential, at, day, 5, of, culture])]). relacion([sujeto(['None', of, the, genes, examined, were]), verbo([expressed]), complemento([in, purified, 'Rho-bright', or, 'Rho-dull', cells])]). relacion([sujeto(['The', only, exception, was, 'GATA1', which, was]), verbo([expressed]), complemento([at, maximal, levels, in, 'Rho-bright', cells, at, the, onset, of, culture])]). relacion([sujeto(['Rho-dull', cells, did, not]), verbo([express]), complemento(['GATA1', before, day, 3, of, culture, '(', maximal, expression, at, days, 10, -, 15, ')'])]). relacion([sujeto(['Activation', of, 'GATA1', and, 'EpoR', was, observed, in, all, growth, of, mRNA, for, the, two, genes]), verbo([expressed]), complemento([by, the, cells])]). relacion([sujeto(['These', results, indicate, that, 'GATA1', is]), verbo([activated]), complemento([at, the, transition, point, between, 'HSCs', and, pluripotent, progenitor, cells, and, 'erythroid-specific', 'GATA1', regulation, involves, activation, of, the, distal, 'GATA1', promoter])]). relacion([sujeto(['The', present, study, examines, genetic, 'mechanism(s)', possibly]), verbo([involved]), complemento([in, the, observed, 3, '\'', -, 'azido-3\'-deoxythymidine', '(', 'AZT)-induced', inhibition, of, globin, gene, transcription, by, evaluating, the, direct, phenotypic, erythroid, effects, of, 'AZT', on, 'erythroid-specific', transcription, factors, which, regulate, globin, gene, promoters])]). relacion([sujeto(['In', vitro]), verbo([binding]), complemento([of, 'GATA-1', or, 'NFE-2', to, its, consensus, sequence, was, decreased, in, the, presence, of, 'AZT', reaching, a, maximum, inhibition, as, early, as, 24, h, after, 'AZT', treatment])]). relacion([sujeto(['Nuclear', extracts, from, butyric, 'acid-induced', 'K562', cells, treated, with, an, 'IC50', concentration, of, 'AZT', exhibited, a]), verbo([decrease]), complemento([in, 'GATA-1', and, 'NFE-2', binding, by, approximately, 30, '%', and, 35, '%'])]). relacion([sujeto(['In', 'contrast,', 2, '\'', ',', 3, '\'', -, dideoxycytidine, which]), verbo([inhibits]), complemento([cell, growth, without, affecting, hemoglobin, 'synthesis,', had, no, effect, on, binding, of, 'GATA-1', and, 'NFE-2', factors])]). relacion([sujeto(['Northern', blot, analysis, revealed, a, 25, '%']), verbo([decrease]), complemento([by, 'AZT', in, 'GATA-1', mRNA, 'steady-state', levels, at, 24, h, and, this, inhibitory, effect, was, maintained, until, 72, h, after, drug, addition])]). relacion([sujeto(['A', similar]), verbo([decrease]), complemento([in, 'NFE-2', mRNA, 'steady-state', levels, was, observed, at, 72, h, after, 'AZT', treatment])]). relacion([sujeto(['This', study]), verbo([suggests]), complemento([that, 'AZT', inhibition, of, erythroid, differentiation, is, subsequent, to, a, decrease, of, nuclear, factors, gene, expression, which, affect, their, 'DNA', binding])]). relacion([sujeto(['The', 'GATA-1', proteins, share, identical]), verbo([binding]), complemento([activity, and, form, heterodimers, in, erythroleukemic, cells, but, differ, in, their, transactivation, potential, and, in, their, expression, in, developing, mouse, embryos])]). relacion([sujeto(['Differentiation', of, murine, erythroleukemia, '(', 'MEL)', cells]), verbo([induced]), complemento([by, hexamethylene, bisacetamide, '(', 'HMBA)', and, 'DMSO', was, inhibited, by, several, structurally, unrelated, nitric, oxide, '(', 'NO)-releasing', agents, and, two, 'membrane-permeable', cGMP, analogues])]). relacion([sujeto(['Since', the, effect, of, the, 'NO-releasing', agents, was, augmented, by, a, cGMP, phosphodiesterase, 'inhibitor,', at, least, some, of, their, effect, appeared, to, be]), verbo([mediated]), complemento([by, activation, of, cytosolic, guanylate, cyclase])]). relacion([sujeto(['In', 'HMBA-treated', 'cells,', the, 'NO-releasing', agents, and, cGMP, analogues, reduced, 'beta-globin', and, 'delta-aminolevulinate', synthetase, mRNA, expression, and]), verbo([inhibited]), complemento([the, late, 'down-regulation', of, 'c-myb', mRNA, that, is, required, for, 'HMBA-induced', differentiation, of, 'MEL', 'cells;', the, regulation, of, 'c-myc', mRNA, was, not, changed, by, the, drugs])]). relacion([sujeto(['Nuclear', 'run-off', analyses, showed, that, the, drugs]), verbo([inhibited]), complemento([the, 'HMBA-induced', changes, in, 'beta-globin', and, 'c-myb', transcription, 'rates,', and, transient, transfection, of, a, reporter, gene, construct, demonstrated, that, the, drugs, inhibited, 'HMBA-inducible', enhancer, function, of, the, 'alpha-globin', control, 'region,', which, contains, binding, sites, for, the, erythroid, transcription, factors, 'NF-E2', and, 'GATA-1'])]). relacion([sujeto(['The', 'NO-releasing', agents, and, cGMP, analogues, largely]), verbo([prevented]), complemento(['HMBA-induced', increases, in, 'DNA', binding, of, 'NF-E2,', whereas, 'DNA', binding, of, 'GATA-1', and, 'SP-1', was, not, affected])]). relacion([sujeto([2, 'region,', we]), verbo([have]), complemento([identified, a, novel, gene, '(', 'RBM3)', that, encodes, a, polypeptide, with, high, sequence, similarity, to, a, group, of, proteins, that, bind, to, 'RNA'])]). relacion([sujeto(['Its', putative, 'RNA-binding', domain, most, closely, resembles, that, of, two, previously, characterized, human, 'RNA-binding', 'proteins,', 'YRRM,', the, gene, for, which]), verbo([has]), complemento([been, implicated, in, 'azoospermia,', and, hnRNP, 'G,', a, 'glycoprotein,', also, identified, as, an, 'auto-antigen'])]). relacion([sujeto(['The', homology, of, 'RMB3', in, both, sequence, and, size, to, an, 'RNA']), verbo([binding]), complemento([protein, from, 'maize,', 'AAIP', ',', suggests, that, it, functions, in, a, fundamental, pathway, conserved, from, plants, to, mammals])]). relacion([sujeto(['Retrovirus-mediated', gene, transfer, was, used, to, study, the, effects, of, dysregulated, expression, of, the, 'zinc-finger', transcription, 'factor,', 'GATA-1,', which]), verbo([has]), complemento([been, shown, to, be, required, for, erythropoiesis])]). relacion([sujeto(['At', 16, weeks, 'posttransplant,', animals, that, received, cells, transduced, by, the, 'GATA-1', virus]), verbo([maintained]), complemento([a, lower, white, blood, cell, '(', 'WBC)', count, and, absolute, neutrophil, count, '(', 'ANC)', and, a, higher, red, blood, cell, '(', 'RBC)', count, than, control, animals, that, received, cells, transduced, with, a, virus, containing, a, neor, gene])]). relacion([sujeto(['Erythropoiesis', was]), verbo([stimulated]), complemento([in, 'GATA-1', and, control, animals, by, phlebotomy])]). relacion([sujeto(['GATA-1', animals]), verbo([required]), complemento([more, extensive, phlebotomy, to, reach, a, hematocrit, less, than, 25, and, their, hematocrit, returned, to, normal, levels, sooner, than, control, animals])]). relacion([sujeto(['These', data]), verbo([suggest]), complemento([that, dysregulated, expression, of, 'GATA-1', in, primitive, hematopoietic, cells, enlarges, the, pool, of, 'epo-responsive', erythroid, progenitor, cells])]). relacion([sujeto(['Extraembryonic', migration]), verbo([has]), complemento([previously, been, 'documented,', but, the, origin, and, migration, of, intraembryonic, hematopoietic, cells, have, not, been, visualized])]). relacion([sujeto(['In', this, 'report,', we]), verbo([have]), complemento([isolated, cDNAs, encoding, zebrafish, homologs, of, the, hematopoietic, transcription, factors, 'GATA-1', and, 'GATA-2', and, have, used, these, markers, to, determine, that, the, 'IM', is, formed, from, mesodermal, cells, in, a, 'posterior-lateral', position, on, the, yolk, syncytial, layer, of, the, gastrula, yolk, sac])]). relacion([sujeto(['Two', major, subpopulations, were, 'identified:', '(', 1, ')', 'CD33+CD42b+', cells, with, platelet, peroxidase, 'activity,', the, commitment, of, which, to, megakaryocytic, lineage, was, supported, by, an]), verbo([increased]), complemento([expression, of, 'GATA-1', 'mRNA;', '(', 2, ')', 'CD33+CD34+CD7+CD4+', cells, with, immature, 'ultrastructure,', which, could, be, either, immature, megakaryocytic, or, myeloid, cells, with, aberrant, differentiation])]). relacion([sujeto(['Mixed', colonies, containing, megakaryocytes, and, 'monocyte/macrophages', in, the, peripheral, blood]), verbo([suggested]), complemento([the, presence, of, progenitors, common, to, these, subpopulations])]). relacion([sujeto(['None', of, the, patients, with, 'ALL', or, 'CML-lymphoid-BC']), verbo([expressed]), complemento(['SCL'])]). relacion([sujeto(['Among', the, patients, with, 'AML', not]), verbo([expressing]), complemento(['SCL,', a, high, percentage, of, patients, with, 'CD7+', 'AML', and, 'CD19+', 'AML', had, detectable, 'GATA-1,', while, patients, with, 'GATA-1-negative', 'AML', had, the, best, 'CR', rate, '(', 87.5, '%', ')'])]). relacion([sujeto(['Our', results]), verbo([suggest]), complemento([that, the, expression, pattern, of, transcription, factors, reflects, the, lineage, potential, of, leukemia, 'cells,', and, 'GATA-1', and, 'SCL', gene, expression, may, have, prognostic, value, for, the, outcome, of, patients, with, 'AML'])]). relacion([sujeto(['The', transcription, factor, 'GATA-1']), verbo([recognizes]), complemento([a, consensus, motif, present, in, regulatory, regions, of, numerous, 'erythroid-expressed', genes])]). relacion([sujeto(['In', vitro, differentiation, of, 'GATA-1-', embryonic, stem, cells, gives, rise, to, a, population, of, committed, erythroid, precursors, that, exhibit, developmental]), verbo([arrest]), complemento([and, death])]). relacion([sujeto(['This', process, occurs, despite, normal, expression, of, all, known, 'GATA']), verbo([target]), complemento([genes, 'examined,', including, the, erythropoietin, 'receptor,', and, independent, of, detectable, accumulation, of, the, tumor, suppressor, protein, p53])]). relacion([sujeto(['Thus,', in, addition, to, its, established, role, in]), verbo([regulating]), complemento([genes, that, define, the, erythroid, 'phenotype,', 'GATA-1', also, supports, the, viability, of, red, cell, precursors, by, suppressing, apoptosis])]). relacion([sujeto(['These', results, illustrate, the, multifunctional, nature, of, 'GATA-1', and]), verbo([suggest]), complemento([a, mechanism, by, which, other, hematopoietic, transcription, factors, may, ensure, the, development, of, specific, lineages])]). relacion([sujeto(['A', possible, role, for, 'RBTN2', in, transcription, during, erythropoiesis]), verbo([has]), complemento([been, investigated])]). relacion([sujeto(['By', using, mammalian, 'two-hybrid', 'analysis,', complexes]), verbo([involving]), complemento(['RBTN2,', 'TAL1,', and, 'GATA1,', together, with, 'E47,', the, basic, 'helix-loop-helix', heterodimerization, partner, of, 'TAL1,', could, be, demonstrated])]). relacion([sujeto(['Thus,', a, molecular, link, exists, between, three, proteins, crucial, for, 'erythropoiesis,', and, the, data]), verbo([suggest]), complemento([that, variations, in, amounts, of, complexes, involving, 'RBTN2,', 'TAL1,', and, 'GATA1', could, be, important, for, erythroid, differentiation])]). relacion([sujeto(['We']), verbo([have]), complemento([examined, binding, of, the, nuclear, protein, 'HMG-I', to, the, human, 'gamma-globin', promoter])]). relacion([sujeto(['We']), verbo([find]), complemento([that, 'HMG-I', binds, preferentially, to, the, more, 3, '\'', of, a, pair, of, 'GATA', motifs, in, the, 'gamma-globin', 'promoter;', this, paired, motif, is, bound, by, the, erythroid, factor, 'GATA-1'])]). relacion([sujeto(['A', naturally, occurring, mutation, '(', -, 175, 'T-C)', in, the, area]), verbo([bound]), complemento([by, 'HMG-I', results, in, overexpression, of, 'gamma-globin', in, adult, red, blood, cells, '(', 'HPFH)', and, 'up-regulation', of, the, 'gamma-globin', promoter, in, in, vitro, expression, 'assays;', 'HMG-I', does, not, bind, to, this, mutant, sequence])]). relacion([sujeto(['A', survey, of, 'GATA', motifs, from, other, globin, 'cis-elements', demonstrates, 'HMG-I']), verbo([binding]), complemento([to, most, of, them])]). relacion([sujeto(['These', findings, implicate, 'HMG-I', in, the, 'HPFH', 'phenotype;', we, speculate, that, it, may]), verbo([participate]), complemento([in, the, formation, of, multiprotein, complexes, that, regulate, globin, gene, expression])]). relacion([sujeto(['We']), verbo([have]), complemento([constructed, two, 'YAC', contigs, in, the, 'Xp11'])]). relacion([sujeto(['We']), verbo([have]), complemento([used, plasmid, 'rescue,', inverse, 'PCR,', and, 'Alu-PCR', to, generate, 20, novel, markers, from, this, 'region,', 1, of, which, is, 'polymorphic,', and, have, positioned, these, relative, to, one, another, on, the, basis, of, 'YAC', analysis])]). relacion([sujeto(['In', 'addition,', we]), verbo([have]), complemento([constructed, a, 'rare-cutter', restriction, map, for, a, 710, -, kb, region, of, the, 'DXS255-DXS146', contig, and, have, identified, three, 'CPG', islands])]). relacion([sujeto(['These', contigs, and, new, markers, will]), verbo([provide]), complemento([a, useful, resource, for, more, detailed, analysis, of, 'Xp11'])]). relacion([sujeto(['The', mouse, 'WASP', 'gene,', the, homolog, of, the, gene, mutated, in, 'Wiskott-Aldrich', 'syndrome,']), verbo([has]), complemento([been, isolated, and, sequenced])]). relacion([sujeto(['The', genomic, structure, of, the, mouse, 'WASP', gene, is]), verbo([expressed]), complemento([as, an, approximately, 2.4, -, kb, mRNA, in, thymus, and, spleen])]). relacion([sujeto(['This', localization, makes, 'Wasp', a, candidate, for, involvement, in, 'scurfy,', a, 'T', 'cell-mediated', fatal, lymphoreticular, disease, of, mice, that]), verbo([has]), complemento([previously, been, proposed, as, a, mouse, homolog, of, 'Wiskott-Aldrich', syndrome])]). relacion([sujeto(['Thrombopoietin', '(', 'Tpo)', is, a, cytokine, that, specifically]), verbo([regulates]), complemento([megakaryocyte, maturation, and, platelet, production])]). relacion([sujeto(['To', study, 'Tpo-induced', megakaryocyte, 'differentiation,', a, mouse, cell, line, 'FD-TPO,', which]), verbo([responds]), complemento([and, grows, with, 'Tpo,', was, established, from, a, 'interleukin-3-dependent', hematopoietic, progenitor, cell, line, 'FDC-P2'])]). relacion([sujeto(['The', 'FD-TPO', 'cells,']), verbo([expressing]), complemento([endogenous, 'Tpo', 'receptor,', grew, with, 'Tpo', in, a, 'dose-dependent', manner])]). relacion([sujeto(['Further,', 'Tpo', stimulation, dramatically]), verbo([induced]), complemento([expression, of, 'megakaryocyte/erythroid-specific', transcription, factors, 'GATA-1', and, 'NF-E2', in, 'FD-TPO', cells])]). relacion([sujeto(['Flow', cytometry, analysis, demonstrated, that, expression, of, 'platelet-specific', cell, surface, antigens, including, 'CD61', '(', 'GPIIIa)', dramatically]), verbo([increased]), complemento([in, 'Tpo-stimulated', 'FD-TPO', cells, and, that, expression, of, 'myeloid-specific', 'antigens,', 'Gr-1', and, 'Mac-1,', decreased])]). relacion([sujeto(['Therefore,', we, concluded, that, the]), verbo([binding]), complemento([of, 'Tpo', to, 'FD-TPO', cells, induces, not, only, cell, growth, but, also, differentiation, into, mature, 'megakaryocyte-like', 'cells,', and, thus, this, cell, line, was, found, to, be, useful, for, the, study, of, 'Tpo', 'receptor-mediated', growth, and, differentiation, signals])]). relacion([sujeto(['The', 'SCL/TAL-1', gene, encodes, a, basic, 'helix-loop-helix', transcription, factor, that, is]), verbo([expressed]), complemento([in, multipotent, hematopoietic, progenitors, before, lineage, commitment])]). relacion([sujeto(['Its', expression, is]), verbo([maintained]), complemento([during, differentiation, along, 'erythroid,', 'mast,', and, megakaryocytic, 'lineages,', but, is, repressed, after, commitment, to, nonexpressing, lineages])]). relacion([sujeto(['To', begin, to, address, the, molecular, mechanisms, underlying, this, complex, pattern, of, 'expression,', we]), verbo([have]), complemento([studied, the, regulation, of, the, murine, 'SCL', promoter, in, erythroid, and, 'T-cell', lines])]). relacion([sujeto(['Conserved', 'GATA', '(', -, 37, ')', ',', 'MAZ', '(', +, 242, ')', ',', and, 'ETS', '(', +, 264, ')', motifs, were, all, shown, to, contribute, to, 'SCL', promoter, activity, in, erythroid, 'cells,', but, several, other, motifs, were, not]), verbo([required]), complemento([for, full, promoter, activity])]). relacion([sujeto(['The', pattern, of, complexes]), verbo([binding]), complemento([to, the, +, 242, 'MAZ', and, +, 264, 'ETS', sites, were, the, same, in, erythroid, and, 'T', cells])]). relacion([sujeto(['However,', 'GATA-1']), verbo([bound]), complemento([the, -, 37, 'GATA', site, in, erythroid, 'cells,', whereas, in, 'T', cells, 'GATA-3', was, only, able, to, bind, 'weakly,', if, at, all])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, inactivity, of, 'SCL', promoter, 1, a, in, 'T', cells, reflected, the, absence, of, 'GATA-1', rather, than, the, presence, of, 'trans-dominant', negative, regulators])]). relacion([sujeto(['Erythropoietin', '(', 'Epo),', the, primary, regulator, of, the, production, of, erythroid, 'cells,']), verbo([acts]), complemento([by, binding, to, a, cell, surface, receptor, '(', 'EpoR)', on, erythroid, progenitors])]). relacion([sujeto(['In', erythroid, cells, most, of, the, transcription, activity, was, contained, in, a, 150, bp, promoter, fragment, with]), verbo([binding]), complemento([sites, for, transcription, factors, 'AP2,', 'Sp1', and, the, 'erythroid-specific', 'GATA-1'])]). relacion([sujeto(['The', 'GATA-1', and, 'Sp1']), verbo([binding]), complemento([sites, in, this, promoter, lacking, a, 'TATA', sequence, were, necessary, for, a, high, level, of, transcription, activation])]). relacion([sujeto(['Protein-DNA']), verbo([binding]), complemento([studies, suggested, that, 'Sp1', and, two, other, 'CCGCCC', binding, proteins, from, erythroid, and, 'non-erythroid', cells, could, bind, to, the, 'Sp1', binding, motif])]). relacion([sujeto(['By']), verbo([increasing]), complemento(['GATA-1', levels, via, 'co-transfection,', we, were, able, to, transactivate, the, hEpoR, promoter, in, 'K562', cells, and, 'non-erythroid', 'cells,', but, not, in, the, highly, active, 'OCIM1', 'cells,', although, 'GATA-1', mRNA, levels, were, comparable, in, 'OCIM1', and, 'K562'])]). relacion([sujeto(['Interestingly,', when, we, mutated, the, 'Sp1', 'site,', resulting, in, a, marked]), verbo([decrease]), complemento([in, hEpoR, promoter, 'activity,', we, could, restore, transactivation, by, increasing, 'GATA-1', levels, in, 'OCIM1', cells])]). relacion([sujeto(['These', data]), verbo([suggest]), complemento([that, while, 'GATA-1', can, transactivate, the, 'EpoR', 'promoter,', the, level, of, hEpoR, gene, expression, does, not, depend, on, 'GATA-1', alone])]). relacion([sujeto(['Rather,', hEpoR, transcription, activity, depends, on, coordination, between, 'Sp1', and, 'GATA-1', with, other, 'cell-specific', 'factors,', including, possibly, other, 'Sp1-like']), verbo([binding]), complemento(['proteins,', to, provide, high, 'level,', 'tissue-specific', expression])]). relacion([sujeto(['The', murine, homologues, of, the, loci, for, 'McLeod', syndrome, '(', 'XK),', 'Dent\'s', disease, '(', 'CICN5),', and, synaptophysin, '(', 'SYP)']), verbo([have]), complemento([been, mapped, to, the, proximal, region, of, the, mouse, 'X', chromosome, and, positioned, with, respect, to, other, conserved, loci, in, this, region, using, a, total, of, 948, progeny, from, two, separate, 'Mus', musculus, x, 'Mus', spretus, backcrosses])]). relacion([sujeto(['In', the, 'mouse,', the, order, of, loci, and, evolutionary, breakpoints, '(', 'EB)']), verbo([has]), complemento([been, established, as, 'centromere-(DXWas70,', 'DXHXF34h)-EB-Clcn5-(Syp,', 'DXMit55,', 'DXMit26)-Tfe3-Gata1-EB-Xk-Cybb-telomere'])]). relacion([sujeto(['In', the, proximal, region, of, the, human, 'X', chromosome, short, 'arm,', the, position, of, evolutionary, breakpoints, with, respect, to, key, loci]), verbo([has]), complemento([been, established, as, 'DMD-EB-XK-PFC-EB-GATA1-C1CN5-EB-DXS1272E-ALAS2-E', 'B-DXF34-centromere'])]). relacion([sujeto(['These', data]), verbo([have]), complemento([enabled, us, to, construct, a, 'high-resolution', genetic, map, for, the, approximately, 3, -, cM, interval, between, 'DXWas70', and, 'Cybb', on, the, mouse, 'X', 'chromosome,', which, encompasses, 10, loci])]). relacion([sujeto(['This', detailed, map, demonstrates, the, power, of, 'high-resolution', genetic, mapping, in, the, mouse, as, a, means, of, determining, locus, order, in, a, small, chromosomal, region, and, of]), verbo([providing]), complemento([an, accurate, framework, for, the, construction, of, physical, maps])]). relacion([sujeto(['The', 'EVI1', gene, is]), verbo([activated]), complemento([by, chromosomal, translocations, and, inversions, in, approximately, 5, '%', of, human, acute, myeloid, leukemia, '(', 'AML)', and, by, retroviral, insertion, in, approximately, 20, '%', of, murine, myeloid, leukemias])]). relacion([sujeto(['EVI1', encodes, a]), verbo([nuclear]), complemento(['DNA-binding', protein, having, 10, zinc, finger, motifs, in, two, noncontiguous, domains, consisting, of, an, 'amino-terminal', domain, of, seven, fingers, and, a, carboxyl, domain, containing, three, fingers])]). relacion([sujeto(['To', evaluate, the, sequence, specificity, of, 'Evi-1']), verbo([binding]), complemento([and, potentially, identify, genomic, 'targets,', 'whole-genome', 'PCR', was, utilized, to, isolate, multiple, 'Sau3A', fragments, which, specifically, bind, to, the, 'amino-terminal', zinc, finger, domain])]). relacion([sujeto(['The', majority, of, these, clones, represented, single, copy, sequences, and, virtually, all, contained, variable, numbers, of, repeats, of, the, 'GATA', 'motif,', the]), verbo([target]), complemento([sequence, for, the, 'erythroid-specific', transcription, factor, 'GATA-1'])]). relacion([sujeto(['GST/Evi-1', fusion, proteins, containing, the, 'amino-terminal', domain, of, zinc, fingers]), verbo([bound]), complemento([the, 'GATA', motif, in, these, clones, as, well, as, to, those, present, in, the, human, 'gamma-globin', 'promoter,', similar, to, the, binding, of, purified, 'GATA-1', protein])]). relacion([sujeto(['By', obtaining, corresponding, large, genomic, clones, for, eight, of, these, 'fragments,', transcription, units, were]), verbo([found]), complemento([associated, with, two])]). relacion([sujeto(['The', second, is, a, novel, gene, whose, expression, is, repressed, in, murine, myeloid, cell, lines, that]), verbo([express]), complemento(['Evi-1'])]). relacion([sujeto(['Thus', studies, on, the, transcriptional, regulation, of, this, gene, may]), verbo([provide]), complemento([helpful, information, on, the, mechanisms, controlling, cell, specificity, and, differentiation, of, this, lineage])]). relacion([sujeto(['In', previous, 'experiments,', the, promoter, of, 'GPIIb', gene, was, isolated, and, we]), verbo([have]), complemento([shown, that, a, fragment, extending, 643, bp, upstream, the, transcription, start, site, was, able, to, control, the, cell, specificity, of, a, reporter, gene, in, transfection, experiments, of, different, permanent, cell, lines])]). relacion([sujeto(['Most', of, the, transcriptional, activity, is, contained, in, an, enhancer, containing]), verbo([binding]), complemento([sites, for, members, of, the, 'GATA', and, ets, transcription, factors, families])]). relacion([sujeto(['The', transcription, factor, 'GATA1', is, not, only, a, major, regulator, of, the, transcription, of, erythroid, 'genes,', but, it, also]), verbo([regulates]), complemento([the, expression, of, 'GPIIb', and, other, megakaryocytic, genes])]). relacion([sujeto(['We']), verbo([suggest]), complemento([that, the, lineage, specificity, and, the, temporal, activation, of, 'GPIIb', gene, during, hematopoiesis, rely, on, the, activity, of, a, repressor, that, has, been, identified, on, the, promoter])]). relacion([sujeto(['To', test, this, 'hypothesis,', we]), verbo([have]), complemento([developed, a, cell, model, allowing, the, study, of, the, megakaryocytes, differentiation, from, very, immature, progenitors, to, fully, differentiated, cells])]). relacion([sujeto(['We']), verbo([have]), complemento([obtained, megakaryocytes, together, with, erythrocytic, and, 'granulo-macrophagic', cells])]). relacion([sujeto(['The', transfection, in, these, 'ES', cells, of, 'GPIIb', promoter, constructs, mutated, or, not, on, different, 'regions,', including, the, repressor, element, will]), verbo([provide]), complemento([important, information, on, the, mechanisms, controlling, gene, activation, or, repression, during, megakaryocyte, differentiation])]). relacion([sujeto(['Northern', blot, analysis, of, 'PB', cells, from, five, 'JCML', patients, indicated, levels, of, 'GATA-1', transcripts, much, higher, than, those, usually]), verbo([found]), complemento([in, other, types, of, leukemic, 'cells,', and, 'S1', nuclease, protection, assay, detected, significantly, increased, expression, of, 'gamma-globin', mRNA])]). relacion([sujeto(['Acute', megakaryoblastic, leukaemia, '(', 'M7)', and, transient, myeloproliferative, disorder, in, 'Down\'s', syndrome, '(', 'TMD)', are, characterized, by, rapid, growth, of, abnormal, blast, cells, which]), verbo([express]), complemento([megakaryocytic, markers])]). relacion([sujeto(['Erythroid-specific', mRNAs, encoding, 'gamma-globin', and, erythroid, 'delta-aminolevulinate', synthase, were]), verbo([found]), complemento([to, be, expressed, in, blasts, from, most, of, these, 'cases,', indicating, that, majorities, of, the, blasts, in, 'M7', and, 'TMD', cases, have, erythroid, and, megakaryocytic, phenotypes])]). relacion([sujeto(['We', also]), verbo([found]), complemento([that, mRNAs, encoding, 'GATA-1', and, 'GATA-2', are, expressed, in, all, these, cases])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, 'M7', blasts, and, 'TMD', blasts, correspond, to, the, 'erythroid/megakaryocytic', bipotential, progenitor, cells])]). relacion([sujeto(['Chromosomal', abnormalities, at, the, 3, q26, 'region,', where, the, 'EVI1', gene, is, 'located,', were]), verbo([found]), complemento([in, one, patient, with, 'MDS', and, two, patients, with, 'CML', myelomegakaryoblast, crisis, who, had, 'EVI1', expression])]). relacion([sujeto(['In', patients, with, 'post-MDS', 'AML,', 'EVI1', expression, was, not, always]), verbo([associated]), complemento([with, a, 3, q26, 'abnormality,', whereas, 'EVI1', expression, in, 'CML', myelomegakaryoblast, crisis, was, often, linked, to, a, 3, q26, abnormality])]). relacion([sujeto(['Our', results]), verbo([suggest]), complemento([that, the, leukemogenic, role, of, 'EVI1', expression, may, differ, between, 'post-MDS', 'AML', and, 'leukemia,', with, 'EVI1', expression, associated, with, a, 3, q26, abnormality])]). relacion([sujeto(['High-dose', estrogen, administration]), verbo([induces]), complemento([anemia, in, mammals])]). relacion([sujeto(['In', 'chickens,', estrogens]), verbo([stimulate]), complemento([outgrowth, of, bone, 'marrow-derived', erythroid, progenitor, cells, and, delay, their, maturation])]). relacion([sujeto(['This', delay, is]), verbo([associated]), complemento([with, 'down-regulation', of, many, erythroid, 'cell-specific', 'genes,', including, 'alpha-', and, 'beta-globin,', band, 3, ',', band, 4.1, ',', and, the, erythroid, 'cell-specific', histone, 'H5'])]). relacion([sujeto(['To', address, potential, mechanisms, by, which, estrogens]), verbo([suppress]), complemento(['erythropoiesis,', we, have, examined, their, effects, on, 'GATA-1,', an, erythroid, transcription, factor, that, participates, in, the, regulation, of, the, majority, of, erythroid, 'cell-specific', genes, and, is, necessary, for, full, maturation, of, erythrocytes])]). relacion([sujeto(['ER-mediated', repression, of, 'GATA-1', activity, occurs, on, an, artificial, promoter, containing, a, single, 'GATA-binding', 'site,', as, well, as, in, the, context, of, an, intact, promoter, which, is, normally]), verbo([regulated]), complemento([by, 'GATA-1'])]). relacion([sujeto(['GATA-1', and, 'ER']), verbo([bind]), complemento([to, each, other, in, vitro, in, the, absence, of, 'DNA'])]). relacion([sujeto(['In', coimmunoprecipitation, experiments, using, transfected, 'COS', 'cells,', 'GATA-1', and, 'ER']), verbo([associate]), complemento([in, a, 'ligand-dependent', manner])]). relacion([sujeto(['Mapping', experiments, indicate, that, 'GATA-1', and, the, 'ER', form, at, least, two, 'contacts,', which]), verbo([involve]), complemento([the, finger, region, and, the, 'N-terminal', activation, domain, of, 'GATA-1'])]). relacion([sujeto(['We', speculate, that, estrogens, exert, effects, on, erythropoiesis, by]), verbo([modulating]), complemento(['GATA-1', activity, through, 'protein-protein', interaction, with, the, 'ER'])]). relacion([sujeto(['Interference', with, 'GATA-binding', proteins, may, be, one, mechanism, by, which, steroid, hormones]), verbo([modulate]), complemento([cellular, differentiation])]). relacion([sujeto(['The', mRNA, for, the, 'Duffy', blood, group, 'antigen,', the, erythrocyte, receptor, for, the, 'Plasmodium', vivax, malaria, 'parasite,']), verbo([has]), complemento([recently, been, cloned, and, shown, to, encode, a, widely, expressed, chemokine, receptor])]). relacion([sujeto(['This', mutation, impairs, the, promoter, activity, in, erythroid, cells, by, disrupting, a]), verbo([binding]), complemento([site, for, the, 'GATA1', erythroid, transcription, factor])]). relacion([sujeto(['With', the, recent, characterization, of, the, 'FY*A', and, 'FY*B', 'alleles,', these, findings]), verbo([provide]), complemento([the, molecular, basis, of, the, 'Duffy', blood, group, system, and, an, explanation, for, the, 'erythroid-specific', repression, of, the, 'DARC', gene, in, 'Duffy-negative', individuals])]). relacion([sujeto(['We']), verbo([have]), complemento([studied, gene, expression, of, 'GATA-1,', 'GATA-2,', and, 'SCL,', which, are, known, as, 'cell-specific', transcription, 'factors,', in, 110, various, leukemias, consisted, of, 76, patients, with, acute, myeloid, leukemia, '(', 'AML),', 19, with, acute, lymphoblastic, leukemia, '(', 'ALL),', and, 15, with, chronic, myeloid, leukemia, '(', 'CML)', in, blast, crisis, by, the, revearse, 'transcription-polymerase', chain, reaction, assay])]). relacion([sujeto(['Leukemia', in, this, group, is, considered, to]), verbo([have]), complemento([a, capability, to, differentiate, into, myeloid, and, lymphoid, lineages])]). relacion([sujeto(['Our', data]), verbo([suggest]), complemento([that, the, expression, pattern, of, transcription, factors, reflects, lineage, potential, in, leukemia, 'cells,', leading, to, classification, of, leukemias])]). relacion([sujeto(['The', expression, of, the, major, erythroid, 'DNA-binding', protein, 'GATA-1', was, studied, during, erythropoietin, and, chemically]), verbo([induced]), complemento([erythroid, differentiation, of, 'J2E', and, murine, erythroleukemia, '(', 'MEL)', cells])]). relacion([sujeto(['An']), verbo([increase]), complemento([in, 'GATA-1', mRNA, levels, was, observed, shortly, after, hormonal, stimulation, of, 'J2E', 'cells,', due, to, increased, transcription, and, not, stabilization, of, the, 'short-lived', transcripts])]). relacion([sujeto(['Concomitantly,', an]), verbo([increase]), complemento([in, protein, capable, of, binding, to, the, 'GATA', motif, was, detected])]). relacion([sujeto(['Similarly,', dimethyl, sulphoxide, induction, of, 'MEL', cells, produced, a, transient]), verbo([decrease]), complemento([in, 'GATA-1', mRNA])]). relacion([sujeto(['Surprisingly,', these]), verbo([decreases]), complemento([in, mRNA, were, not, reflected, in, alterations, to, 'GATA-1', protein, 'content,', or, the, ability, of, the, transcription, factor, to, bind, 'DNA'])]). relacion([sujeto(['We', used, reverse, transcriptase, polymerase, chain, reaction, to, assay, the, 'c-kitBR', subset, and, the, subsets]), verbo([expressing]), complemento([low, '(', 'c-kitDULL)', and, no, '(', 'c-kitNEG)', 'c-kit', receptor, for, expression, of, mRNA, encoding, hematopoietic, growth, factor, receptors, and, transcription, factors])]). relacion([sujeto(['The', 'c-kitDULL', cells, had, 47, -, 58, '%', of, the, 'c-kit', mRNA]), verbo([found]), complemento([in, 'c-kitBR', cells, and, the, 'c-kitNEG', cells, had, 4, -, 9, '%', of, the, 'c-kit', mRNA, present, in, 'c-kitBR', cells])]). relacion([sujeto(['We', conclude, from, these, findings, that, 'PHSCs', are, programmed, to]), verbo([interact]), complemento([with, stem, cell, 'factor,', 'IL-3,', and, 'IL-6', but, not, with, granulocyte, or, macrophage, 'colony-stimulating', factor])]). relacion([sujeto(['These', findings, also, indicate, that, 'GATA-2,', p45, 'NF-E2,', and, 'c-myb', activities, may, be]), verbo([involved]), complemento([in, 'PHSC', maintenance, or, proliferation])]). relacion([sujeto(['An', unresolved, aspect, of, current, understanding, of, erythroid, 'cell-specific', gene, expression, relates, to, how, a, limited, number, of, transcriptional, factors, cooperate, to, direct, 'high-level', expression]), verbo([mediated]), complemento([by, 'cis-regulatory', elements, separated, over, large, distances, within, globin, loci])]). relacion([sujeto(['In', this, 'report,', we]), verbo([provide]), complemento([evidence, that, 'GATA-1,', the, major, erythroid, transcription, 'factor,', activates, transcription, in, a, synergistic, fashion, with, two, 'Krüppel', family, 'factors,', the, ubiquitous, protein, 'Sp1', and, the, 'erythroid-restricted', factor, 'EKLF', '(', erythroid, 'Krüppel-like', 'factor),', which, recognize, 'GC', 'and/or', 'GT/CACC', motifs])]). relacion([sujeto(['Binding', sites, for, both, 'GATA-1', and, these, 'Krüppel', proteins, '(', especially, 'Sp1)', are]), verbo([found]), complemento([in, close, association, in, the, promoters, and, enhancers, of, numerous, erythroid, 'cell-expressed', genes, and, appear, to, cooperate, in, directing, their, expression])]). relacion([sujeto(['We']), verbo([have]), complemento([shown, that, 'GATA-1', interacts, physically, with, 'Sp1', and, 'EKLF', and, that, interactions, are, mediated, through, their, respective, 'DNA-binding', domains])]). relacion([sujeto(['Finally,', the, formation, of, 'GATA-1-SP1', complexes, was, demonstrated, in, vivo, by, the, ability, of, 'Sp1', to]), verbo([recruit]), complemento(['GATA-1', to, a, promoter, in, the, absence, of, 'GATA-binding', sites])]). relacion([sujeto(['These', experiments]), verbo([provide]), complemento([the, first, evidence, for, functionally, important, 'protein-protein', interactions, involved, in, erythroid, 'cell-specific', expression, and, suggest, a, mechanism, by, which, 'DNA', loops, between, locus, control, regions, and, globin, promoters, '(', or, 'enhancers)', might, be, formed, or, stabilized])]). relacion([sujeto(['We']), verbo([have]), complemento([explored, the, expression, of, the, transcription, factors, 'GATA-1,', 'GATA-2,', and, 'NF-E2', in, purified, early, hematopoietic, progenitor, cells, '(', 'HPCs)', induced, to, gradual, unilineage, erythroid, or, granulocytic, differentiation, by, growth, factor, stimulus])]). relacion([sujeto(['GATA-2', mRNA, and, 'protein,', already]), verbo([expressed]), complemento([in, quiescent, 'HPCs,', is, rapidly, induced, as, early, as, 3, h, after, growth, factor, 'stimulus,', but, then, declines, in, advanced, erythroid, and, granulocytic, differentiation, and, maturation])]). relacion([sujeto(['NF-E2', and, 'GATA-1', mRNAs, and, 'proteins,', though, not, detected, in, quiescent, 'HPCs,', are, gradually]), verbo([induced]), complemento([at, 24, -, 48, h, in, both, erythroid, and, granulocytic, culture])]). relacion([sujeto(['Beginning', at, late, 'differentiation/early', maturation, 'stage,', both, transcription, factors, are, further, accumulated, in, the, erythroid, 'pathway,', whereas, they, are]), verbo([suppressed]), complemento([in, the, granulopoietic, series])]). relacion([sujeto(['Similarly,', the, erythropoietin, receptor, '(', 'EpR)', is]), verbo([induced]), complemento([and, sustainedly, expressed, during, erythroid, 'differentiation,', although, beginning, at, later, times, '(', i])]). relacion([sujeto([',', day, 5, ')', ',', whereas, it, is, barely]), verbo([expressed]), complemento([in, the, granulopoietic, pathway])]). relacion([sujeto(['In', the, first, series, of, functional, 'studies,', 'HPCs', were, treated, with, antisense, oligomers]), verbo([targeted]), complemento([to, transcription, factor, 'mRNA:', inhibition, of, 'GATA-2', expression, caused, a, decreased, number, of, both, erythroid, and, 'granulocyte-monocytic', 'clones,', whereas, inhibition, of, 'NF-E2', or, 'GATA-1', expression, induced, a, selective, impairment, of, erythroid, colony, formation])]). relacion([sujeto(['In', a, second, series, of, functional, 'studies,', 'HPCs', treated, with, retinoic, acid, were]), verbo([induced]), complemento([to, shift, from, erythroid, to, granulocytic, differentiation, '(', 'Labbaye', et, al])]). relacion([sujeto([83, :, 651, -, 656, ')', ;, this, was, coupled, with, abrogation, of, 'GATA-1,', 'NF-E2,', and, 'EpR', expression, and, conversely]), verbo([enhanced]), complemento(['GATA-2', levels])]). relacion([sujeto(['Conversely,', 'NF-E2', and, 'GATA-1', expression, and, function, are, apparently, restricted, to, erythroid, differentiation, and, 'maturation:', their, expression, precedes, that, of, the, 'EpR,', and, their, function, may, be, in, part]), verbo([mediated]), complemento([via, the, 'EpR'])]). relacion([sujeto(['When', transfected, into, 'K562', 'cells,', which]), verbo([express]), complemento(['zeta-globin,', comparable, amounts, of, activity, were, obtained, from, the, -, 557, and, -, 417, 'zeta-luciferase', constructs, and, the, 'alpha-luciferase', constructs, when, no, enhancers, or, the, 'alpha-globin', locus, enhancers, were, used])]). relacion([sujeto(['When', the, constructs, were, transfected, into, 'OCIM1', 'cells,', which, do, not]), verbo([express]), complemento(['zeta-globin,', the, 'zeta-globin', promoters, were, at, best, 20, '%', as, active, as, the, 'alpha-globin', promoters])]). relacion([sujeto(['Electrophoretic', mobility, shift, assays, indicated, that, the, -, 230, 'GATA-1', site]), verbo([has]), complemento([a, relatively, low, affinity, for, 'GATA-1'])]). relacion([sujeto(['This', element]), verbo([requires]), complemento(['GATA-1', and, additional, unknown, factors, for, maximal, activity])]). relacion([sujeto(['To', study, oncogenesis, in, the, erythroid, 'lineage,', we]), verbo([have]), complemento([generated, transgenic, mice, carrying, the, human, 'c-MYC', 'proto-oncogene', under, the, control, of, mouse, 'GATA-1', regulatory, sequences])]). relacion([sujeto(['Six', transgenic, lines]), verbo([expressed]), complemento([the, transgene, and, displayed, a, clear, oncogenic, phenotype])]). relacion([sujeto(['Transgenic', progeny, of, the, sixth, 'founder,', while, also]), verbo([expressing]), complemento([the, 'transgene,', remained, asymptomatic, for, more, than, 8, 'mo,', whereupon, members, of, this, line, began, to, develop, late, onset, erythroleukemia])]). relacion([sujeto(['Cell', lines, were, established, from, five, of, the, six, leukemic, animals, and, these, 'lines,', designated, 'erythroleukemia/c-MYC', '(', 'EMY),', displayed, proerythroblast, morphology, and]), verbo([expressed]), complemento([markers, characteristic, of, the, erythroid, 'lineage,', including, the, erythropoietin, receptor, and, 'beta-globin'])]). relacion([sujeto(['Studies', in, the, surviving, transgenic, line, indicated, 'that,', contrary, to, our, 'expectations,', the, transgene, was, not]), verbo([expressed]), complemento([in, the, mast, cell, lineage])]). relacion([sujeto(['That,', coupled, with, the, exclusive, occurrence, of, erythroleukemia, in, all, the, transgenic, 'lines,']), verbo([suggests]), complemento([that, the, 'GATA-1', promoter, construct, we, have, used, includes, regulatory, sequences, necessary, for, in, vivo, erythroid, expression, only])]). relacion([sujeto(['Additional', sequences, would, appear, to, be]), verbo([required]), complemento([for, expression, in, mast, cells])]). relacion([sujeto(['Further,', our, results, show, that, 'c-MYC', can, efficiently, transform, erythroid, precursors, if]), verbo([expressed]), complemento([at, a, vulnerable, stage, of, their, development])]). relacion([sujeto(['We']), verbo([found]), complemento([a, deletion, of, the, distal, part, of, one, chromosome, 11, '[', 'del(11)q23'])]). relacion([sujeto([3, -, -, &, 'gt;qter]', that, was, detected, by, cytogenetic, analysis, and, confirmed, by, chromosome, painting, in, the, two, patients, and, also, an]), verbo([increased]), complemento([number, of, bone, marrow, megakaryocytes, '(', 'MKs),', including, numerous, micromegakaryocytes, '(', 'mMKs)', associated, with, a, normal, platelet, life, span])]). relacion([sujeto(['A', normal, number, of, 'MK', colonies, in, culture, was, observed, with, one, third, of, them, containing, a, few, large, 'MKs;', 'however,', these, were, always]), verbo([associated]), complemento([with, mMKs, identified, by, immunologic, staining])]). relacion([sujeto(['These', giant, 'alpha-granules', were, unable, to]), verbo([release]), complemento([their, contents, after, stimulation, by, 'thrombin,', in, contrast, to, platelets, with, normal, morphology])]). relacion([sujeto(['Abnormalities', in, bone, marrow, 'MK', maturation, that, were, detected, at, the, electron, microscopic, level, and, that]), verbo([led]), complemento([to, lysis, of, numerous, 'MKs', were, responsible, for, thrombocytopenia, and, were, similar, in, both, patients])]). relacion([sujeto(['In', 'conclusion,', the, association, of, all, these, abnormalities, constitutes, a, new, familial, platelet, disorder, and, may, present, a, valuable, model, for, exploring, the, role, of, some, genes]), verbo([involved]), complemento([in, the, regulation, of, thrombopoiesis])]). relacion([sujeto(['Tattered', '(', 'Td)', is, an, 'X-linked', dominant, mouse, mutation, that]), verbo([causes]), complemento([prenatal, lethality, in, affected, males])]). relacion([sujeto(['Pedigree', analysis, of, these, animals]), verbo([suggests]), complemento([a, gene, order, of, 'cen-DXWas70-(Td,', 'DXMit26,', 'Gata1,', 'Tcfe3)-(Cybb,', 'Otc)-tel,', where, 'Tcfe3', is, a, transcription, factor, homologous, to, a, gene, involved, in, the, murine, microphthalmia, '(', 'mi)', mutation, '[', 'Hodgkinson', et, al])]). relacion([sujeto(['To', evaluate, 'Tcfe3', as, a, candidate, for, 'Td,', heterozygous, tattered, females, were, crossed, to, xid, males, to, obtain, females, in, which, &, 'gt;', 95, '%', of, 'B', cells]), verbo([expressed]), complemento([genes, solely, from, the, 'Td', 'X', 'Chromosome', '(', 'Chr)'])]). relacion([sujeto(['Fluorescent']), verbo([activated]), complemento([cell, sorting, '(', 'FACS)', analysis, and, 'Western', blotting, of, isolated, splenocytes, from, 'Td/xid', double, heterozygotes, rule, out, 'Tcfe3', as, a, likely, candidate, for, the, 'Td', mutation])]). relacion([sujeto(['Using', 'J2E', cells, and, the, murine, beta, 'maj-globin', promoter, as, a, 'model,', we]), verbo([have]), complemento([performed, the, first, direct, analyses, of, erythropoietin, '(', 'EPO)-activated', transcription, from, defined, templates])]). relacion([sujeto(['The', -, 346, to, +, 26, beta, maj, promoter, was, shown, to, comprise, a]), verbo([target]), complemento([for, maximal, activation])]). relacion([sujeto(['Mutagenesis', of, a, -, 215, -, bp, 'AGATAA', element, within, this, domain, showed, that, this, effect, did, not]), verbo([require]), complemento(['GATA-1', binding])]). relacion([sujeto(['In', 'contrast,', a, critical, role, for, 'GATA-1', at, a, -, 60, -, bp, '(', 'G)GATAG', element, was, defined, by, mutagenesis, '(', 'GGg-TAG', and, 'TGATAG),', complementation, with, a, synthetic, 'TGATAA', 'element,', and, the, demonstrated, specific]), verbo([binding]), complemento([of, 'GATA-1'])]). relacion([sujeto(['Remarkably,', the, '[', 'TGATAA]4-TATA', 'promoter,', but, not, the, 'TGATAA-CACCC-TATA', 'promoter,', was]), verbo([induced]), complemento([efficiently, by, 'EPO', in, 'J2E', 'cells,', whereas, the, 'TGATAA-CACCC-TATA', promoter, was, highly, induced, by, 'Me2SO', in, 'F-MEL', cells])]). relacion([sujeto(['These', findings]), verbo([suggest]), complemento([that, mechanisms, of, 'EPO-induced', transcription, in, 'J2E', cells, involve, 'GATA-1', and, differ, from, chemically, activated, mechanisms, studied, previously, in, 'F-MEL', cells])]). relacion([sujeto(['Globin', induction, in, 'J2E', cells, was, not]), verbo([associated]), complemento([with, effects, of, 'EPO', on, levels, or, nuclear, translocation, of, 'GATA-1'])]). relacion([sujeto(['However,', hemoglobinization, was]), verbo([induced]), complemento([by, okadaic, 'acid,', 8, -, 'Br-cAMP,', and, 'forskolin,', a, finding, consistent, with, induction, mechanisms, that, may, involve, modulated, 'serine/threonine', phosphorylation])]). relacion([sujeto(['The', onset, of, flowering, is]), verbo([promoted]), complemento([by, long, 'photoperiods,', but, the, constans, '(', 'co)', mutant, flowers, later, than, wild, type, under, these, conditions])]). relacion([sujeto([co, mutations, were, shown, to, affect, amino, acids, that, are]), verbo([conserved]), complemento([in, both, fingers])]). relacion([sujeto(['Some', transgenic, plants, containing, extra, copies, of, 'CO', flowered, earlier, than, wild, 'type,']), verbo([suggesting]), complemento([that, 'CO', activity, is, limiting, on, flowering, time])]). relacion([sujeto(['Double', mutants, were, constructed, containing, co, and, mutations, affecting, gibberellic, acid, 'responses,', meristem, 'identity,', or, phytochrome, 'function,', and, their, phenotypes]), verbo([suggested]), complemento([a, model, for, the, role, of, 'CO', in, promoting, flowering])]). relacion([sujeto(['The', 'Wilms\'', tumor, 'gene,', 'WT1,', is, believed, to, play, a, role, in, hematopoiesis, as, it, is]), verbo([expressed]), complemento([in, the, spleen, and, in, immature, leukemias, in, addition, to, the, developing, genitourinary, system])]). relacion([sujeto(['The', modulation, of, 'WT1', expression, was, examined, in, many, cell, 'types,', and, a, 'hematopoietic-specific', enhancer, element]), verbo([has]), complemento([been, identified])]). relacion([sujeto(['We']), verbo([found]), complemento(['co-expression', of, 'WT1', and, 'GATA-1', mRNA, in, 'K562', cells, and, in, mouse, 'spleen,', suggesting, potential, interactions, between, these, two, transcription, factors])]). relacion([sujeto(['We']), verbo([find]), complemento([that, the, activity, of, the, 3, '\'', 'WT1', enhancer, is, positively, correlated, with, the, expression, of, 'GATA-1'])]). relacion([sujeto(['Gel', shift, competition, experiments, and, transactivation, studies, revealed, that, this, functional, activity, is]), verbo([mediated]), complemento([via, binding, at, a, 'GATA-binding', site, in, the, 'WT1', enhancer])]). relacion([sujeto(['Remarkably,', within, the, hematopoietic, 'compartment,', genes, of, the, 'HOXB', complex, are]), verbo([expressed]), complemento([specifically, in, erythromegakaryocytic, cell, lines, 'and,', for, some, of, 'them,', in, hematopoietic, progenitors])]). relacion([sujeto(['Here,', we]), verbo([report]), complemento([the, study, of, 'HOXB2', gene, transcriptional, regulation, in, hematopoietic, 'cells,', an, initial, step, in, understanding, the, 'lineage-specific', expression, of, the, whole, 'HOXB', complex, in, these, cells])]). relacion([sujeto(['We']), verbo([have]), complemento([isolated, the, 'HOXB2', 5, '\'', -, flanking, sequence, and, have, characterized, a, promoter, fragment, extending, 323, base, pairs, upstream, from, the, transcriptional, start, 'site,', 'which,', in, transfection, 'experiments,', was, sufficient, to, direct, the, 'tissue-specific', expression, of, 'HOXB2', in, the, erythroid, cell, line, 'K562'])]). relacion([sujeto(['In', this, 'fragment,', we]), verbo([have]), complemento([identified, a, potential, 'GATA-binding', site, that, is, essential, to, the, promoter, activity, as, demonstrated, by, point, mutation, experiments])]). relacion([sujeto(['Gel', shift, analysis, revealed, the, formation, of, a, specific, complex, in, both, erythroleukemic, lines, 'K562', and, 'HEL', that, could, be]), verbo([prevented]), complemento([by, the, addition, of, a, specific, antiserum, raised, against, 'GATA-1', protein])]). relacion([sujeto(['These', findings]), verbo([suggest]), complemento([a, regulatory, hierarchy, in, which, 'GATA-1', is, upstream, of, the, 'HOXB2', gene, in, erythroid, cells])]). relacion([sujeto(['Understanding', the, mechanism, of, developmental, regulation, of, hemoglobin, switching]), verbo([has]), complemento([scientific, as, well, as, clinical, relevance, because, of, the, influence, of, fetal, hemoglobin, '(', 'HbF)', production, in, adulthood, on, the, clinical, manifestation, of, thalassemia, and, sickle, cell, anemia])]). relacion([sujeto(['We']), verbo([have]), complemento([previously, found, that, the, normal, developmental, patterns, of, globin, gene, expression, are, recapitulated, in, an, experimental, system, of, primary, cultures, that, support, differentiation, of, erythroid, progenitors])]). relacion([sujeto(['We', further]), verbo([found]), complemento([that, high, activities, of, the, transcriptional, 'activators,', 'GATA-1', and, 'SP1,', are, associated, with, normal, adult, erythroid, differentiation])]). relacion([sujeto(['In', the, present, 'work,', we]), verbo([have]), complemento(['studied,', the, activities, of, 'GATA-1', and, 'SP1', during, differentiation, of, cultured, erythroid, progenitors, derived, from, cord, blood, and, from, fetal, 'livers,', as, well, as, from, beta, 'zero-thalassemia', patients])]). relacion([sujeto(['The', results, showed, high, 'GATA-1']), verbo([binding]), complemento([activity, and, very, low, 'SP1', activity, in, the, fetal, liver, cultures])]). relacion([sujeto(['The', proacrosin, gene, is]), verbo([transcribed]), complemento([in, diploid, spermatogenic, cells, and, translated, in, haploid, round, spermatids])]). relacion([sujeto(['In', order, to, evaluate, sequences, which, are]), verbo([involved]), complemento([in, proacrosin, gene, 'transcription,', 'DNA-protein', interactions, were, analyzed, in, 1.2, kb, of, the, 5, '\'', flanking, region, of, the, rat, gene])]). relacion([sujeto([13, protein]), verbo([binding]), complemento([sites, were, identified, by, 'DNase', 'I', footprinting, using, nuclear, extracts, from, rat, testis, and, 'brain,', respectively])]). relacion([sujeto(['Five', footprints, '(', 'F1,', 'F3,', 'F7,', 'TS2,', 'TS3)', which]), verbo([suggest]), complemento([an, interaction, with, testis, specific, nuclear, factors, were, further, examined, by, gel, retardation, assays])]). relacion([sujeto(['Three', testis, specific]), verbo([binding]), complemento([sites, '(', 'F1,', 'F7,', 'TS2,', located, 472, 'bp,', 697, bp, and, 1004, bp, upstream, of, 'ATG,', 'respectively)', could, be, identified, with, both, methods])]). relacion([sujeto(['The']), verbo([binding]), complemento([site, 'F1', contains, a, motif, which, is, similar, to, a, testis, specific, footprint, found, in, mouse, protamine, 1, gene])]). relacion([sujeto(['The', nucleotide, sequence, of, 'F7', contains, the, recognition, motif, of, an, isoform, of, the, transcription, factor, 'GATA1,', which, is]), verbo([expressed]), complemento([in, testis])]). relacion([sujeto(['The', human, 'epsilon-globin', gene, is]), verbo([transcribed]), complemento([in, erythroid, cells, only, during, the, embryonic, stages, of, development])]). relacion([sujeto(['Expression', of, 'epsilon-globin', 'gene,', 'however,', can, be]), verbo([maintained]), complemento([in, adult, transgenic, mice, following, removal, of, 'DNA', positioned, between, -, 467, and, -, 182, bp, upstream, of, the, 'epsilon-globin', cap, site])]). relacion([sujeto(['We']), verbo([have]), complemento([identified, three, protein, binding, regions, within, this, 'silencer;', a, 'CCACC', motif, around, -, 379, ',', two, overlapping, motifs, for, 'YY1', and, 'GATA', around, -, 269, and, a, 'GATA', motif, around, -, 208, and, we, have, analyzed, their, function, during, development, by, studying, several, mutants, in, transgenic, mice])]). relacion([sujeto(['Mutation', of, the, -, 208, 'GATA', motif, allows, high, 'epsilon-globin', transgene, expression, in, the, adult]), verbo([suggesting]), complemento(['that,', in, addition, to, its, positive, effects, on, 'transcription,', 'GATA-1', also, plays, a, negative, role, in, the, regulation, of, globin, gene, expression, during, development])]). relacion([sujeto(['Repression', of, epsilon, gene, expression, in, the, adult, also]), verbo([requires]), complemento([a, functional, 'YY1', binding, site, at, position, -, 269])]). relacion([sujeto(['Thus,', multiple, 'proteins,', including, 'GATA-1,']), verbo([participate]), complemento([in, the, formation, of, the, epsilon, gene, repressor, complex, that, may, disrupt, the, interaction, between, the, proximal, 'epsilon-promoter', and, the, locus, control, region, '(', 'LCR)', in, definitive, erythroid, cells])]). relacion([sujeto(['The', 'GATA-1', and, 'GATA-2', transcription, 'factors,', which, each, contain, two, homologous, zinc, 'fingers,', are, important, hematopoietic, regulators]), verbo([expressed]), complemento([within, the, 'erythroid,', mast, 'cell,', and, megakaryocytic, lineages])]). relacion([sujeto(['Enforced', expression, of, either, factor, in, the, primitive, myeloid, line, 416, 'B']), verbo([induces]), complemento([megakaryocytic, differentiation])]). relacion([sujeto(['The', features, of, their, structure]), verbo([required]), complemento([for, this, activity, have, been, explored])]). relacion([sujeto(['The', ability, of, 12, 'GATA-1', mutants, to]), verbo([promote]), complemento([416, 'B', maturation, was, compared, with, their, 'DNA-binding', activity, and, transactivation, potential])]). relacion([sujeto(['Differentiation', did, not]), verbo([require]), complemento([any, of, the, seven, serine, residues, that, are, phosphorylated, in, 'vivo,', an, 'N-terminal', region, bearing, the, major, transactivation, 'domain,', or, a, 'C-terminal', segment, beyond, the, fingers])]). relacion([sujeto(['Removal', of, a, consensus]), verbo([nuclear]), complemento([localization, signal, following, the, second, finger, did, not, block, differentiation, or, nuclear, translocation])]). relacion([sujeto(['Remarkably,', only, 69, residues, spanning, the, 'C-terminal', finger, were]), verbo([required]), complemento([to, induce, limited, megakaryocytic, differentiation])]). relacion([sujeto(['Analysis', of, three, 'GATA-2', mutants]), verbo([led]), complemento([to, the, same, conclusion])]). relacion([sujeto(['Endogenous', 'GATA-1', mRNA, was]), verbo([induced]), complemento([by, most, mutants, and, may, contribute, to, differentiation])]). relacion([sujeto(['Because', the, 'GATA-1', 'C-terminal', finger, could]), verbo([bind]), complemento([its, target, site, but, not, transactivate, a, minimal, 'reporter,', it, may, direct, megakaryocytic, maturation, by, derepressing, specific, genes, 'and/or', by, interacting, with, another, protein, which, provides, the, transactivation, function])]). relacion([sujeto(['The', 'beta-like', globin, genes]), verbo([require]), complemento([the, upstream, locus, control, region, '(', 'LCR)', for, proper, expression])]). relacion([sujeto(['We']), verbo([have]), complemento([used, 5, '\'', 'HS4', as, a, model, to, study, the, formation, of, these, 'HSs'])]). relacion([sujeto(['Previously,', we, identified, a, 101, bp, element, that, is]), verbo([required]), complemento([for, the, formation, of, this, 'HS'])]). relacion([sujeto(['This', element]), verbo([binds]), complemento([six, proteins, in, vitro])]). relacion([sujeto(['We', now]), verbo([report]), complemento([a, mutational, analysis, of, the, 'HS4', 'HS-forming', element, '(', 'HSFE)'])]). relacion([sujeto(['This', analysis, indicates, that]), verbo([binding]), complemento([sites, for, the, hematopoietic, transcription, factors, 'NF-E2', and, 'GATA-1', are, required, for, the, formation, of, the, characteristic, chromatin, structure, of, the, 'HS', following, stable, transfection, into, murine, erythroleukemia, cells])]). relacion([sujeto(['Similarly', arranged, 'NF-E2', and, 'GATA']), verbo([binding]), complemento([sites, are, present, in, the, other, 'HSs', of, the, human, 'LCR,', as, well, as, in, the, homologous, mouse, and, goat, sequences, and, the, chicken, 'beta-globin', enhancer])]). relacion([sujeto(['Other', members, of, the, 'GATA', 'family,', which, can]), verbo([bind]), complemento([to, the, same, 'DNA', sequence, 'motif,', are, 'co-expressed', in, several, of, these, hemopoietic, 'lineages,', raising, the, possibility, of, overlap, in, function])]). relacion([sujeto(['To', examine, the, specific, roles, of, 'GATA-1', in, hematopoietic, cell, 'differentiation,', we]), verbo([have]), complemento([tested, the, ability, of, embryonic, stem, 'cells,', carrying, a, targeted, mutation, in, the, 'X-linked', 'GATA-1', 'gene,', to, contribute, to, various, blood, cell, types, when, used, to, produce, chimeric, embryos, or, mice])]). relacion([sujeto(['Previously,', we]), verbo([reported]), complemento([that, 'GATA-1-', mutant, cells, failed, to, contribute, to, the, mature, red, blood, cell, 'population,', indicating, a, requirement, for, this, factor, at, some, point, in, the, erythroid, lineage, '(', 'L'])]). relacion([sujeto(['In', this, 'study,', we]), verbo([have]), complemento([used, in, vitro, colony, assays, to, identify, the, stage, at, which, mutant, erythroid, cells, are, 'affected,', and, to, examine, the, requirement, for, 'GATA-1', in, other, lineages])]). relacion([sujeto(['We']), verbo([found]), complemento([that, the, development, of, erythroid, progenitors, in, embryonic, yolk, sacs, was, unaffected, by, the, 'mutation,', but, that, the, cells, failed, to, mature, beyond, the, proerythroblast, 'stage,', an, early, point, in, terminal, differentiation])]). relacion([sujeto(['GATA-1-', colonies, contained, phenotypically, normal, 'macrophages,', neutrophils, and, 'megakaryocytes,', indicating, that, 'GATA-1', is, not]), verbo([required]), complemento([for, the, in, vitro, differentiation, of, cells, in, these, lineages])]). relacion([sujeto(['GATA-1-', megakaryocytes, were, abnormally, abundant, in, chimeric, fetal, 'livers,']), verbo([suggesting]), complemento([an, alteration, in, the, kinetics, of, their, formation, or, turnover])]). relacion([sujeto(['The', lack, of, a, block, in, terminal, megakaryocyte, differentiation, was, shown, by, the, in, vivo, production, of, platelets]), verbo([expressing]), complemento([the, 'ES', 'cell-derived', 'GPI-1C', isozyme])]). relacion([sujeto(['Mutant', and, 'wild-type', mast, cells, displayed, similar, growth, and, histochemical, staining, properties, after, culture, under, conditions, that]), verbo([promote]), complemento([the, differentiation, of, cells, resembling, mucosal, or, serosal, mast, cells])]). relacion([sujeto([2, ')']), verbo([has]), complemento([been, reported, in, cases, of, papillary, renal, cell, tumors, arising, in, males])]). relacion([sujeto(['In', this, study, two, cell, lines, derived, from, this, tumor, type]), verbo([have]), complemento([been, used, to, indicate, the, breakpoint, region, on, the, 'X', chromosome])]). relacion([sujeto(['Both', cell, lines]), verbo([have]), complemento([the, translocation, in, addition, to, other, rearrangements, and, one, is, derived, from, the, first, female, case, to, be, reported, with, the, 't(X;1)(p11'])]). relacion([sujeto(['Fluorescence', in, situ, hybridization, '(', 'FISH)']), verbo([has]), complemento([been, used, to, position, 'YACs', belonging, to, contigs, in, the, 'Xp11'])]). relacion([sujeto([2, region, the, position, of, the, breakpoint, in, both, cell, lines, was]), verbo([suggested]), complemento([as, 'follows:', 'Xpter-->Xp11'])]). relacion([sujeto(['In', 'Aspergillus', nidulans, the, regulatory, gene, areA, is, responsible, for]), verbo([mediating]), complemento([nitrogen, metabolite, repression])]). relacion([sujeto(['The', areA, product, '(', 'AREA)', represents, an, example, of, the, 'GATA', family, of, 'DNA']), verbo([binding]), complemento(['proteins,', which, are, characterised, by, the, presence, of, a, 'GATA', domain, consisting, of, a, zinc, finger, within, a, highly, conserved, region, of, 52, amino, acids])]). relacion([sujeto(['In', order, to, demonstrate, high, specificity]), verbo([binding]), complemento([of, native, 'AREA', to, 'DNA', containing, the, sequence, -, 'GATA-,', and, investigate, the, presence, in, 'A'])]). relacion([sujeto([nidulans, of, other, proteins, with, related, 'specificities,', we]), verbo([have]), complemento([used, gel, mobility, shift, assays])]). relacion([sujeto(['Both', 'AREA-dependent', and, independent, complexes]), verbo([have]), complemento([been, identified])]). relacion([sujeto(['Strains', bearing, the, 'areA::NC-GATA', 'construct,', which, includes, the, sequence, encoding, both, the, 'N', and, 'C-terminal', domains, of, 'GATA-1,']), verbo([leads]), complemento([to, a, pronounced, increase, in, one, of, two, 'AREA-dependent', complexes, and, implicates, the, 'N-terminal', domain, of, 'GATA-1', in, mediating, 'protein-protein', interactions])]). relacion([sujeto(['We']), verbo([have]), complemento([isolated, and, characterized, the, 5, '\'', -, flanking, region, of, the, gene, for, human, ferrochelatase, '(', 'HFC),', the, last, enzyme, of, the, heme, biosynthetic, pathway])]). relacion([sujeto(['Recognition', sites, for, the, ubiquitous, 'Sp1', family, of, transcription, 'factors,', as, well, as, for, the, 'erythroid-specific', 'trans-acting', factors, 'NF-E2', and, 'GATA-1', were, 'found,', and]), verbo([binding]), complemento([of, regulatory, proteins, to, these, elements, was, analyzed, by, in, vitro, 'DNase', 'I', protection, assays])]). relacion([sujeto(['However,', elimination, of, a, repressor, sequence, lying, between, the, minimal, promoter, and, the, 'erythroid-specific', elements, resulted, in, high, levels, of, expression, in, human, erythroleukemic, 'K562', cells, only, when, the, cis, elements]), verbo([recognized]), complemento([by, 'GATA-1', and, 'NF-E2', were, 'present,', suggesting, that, the, activity, of, these, factors, is, regulated, by, a, downstream, repressor, in, erythroid, cells])]). relacion([sujeto(['GATA-1', is, a, 'cys-2/cys-2', zinc, finger, transcriptional, activator, that, is]), verbo([required]), complemento([for, erythrocyte, development, in, chimeric, mice, and, contributes, to, the, expression, of, all, erythroid, genes, studied, to, 'date,', including, the, erythropoietin, 'receptor,', glycophorin, 'B,', and, porphobilinogen, deaminase, genes])]). relacion([sujeto(['Transactivation', by, 'GATA-1', is]), verbo([mediated]), complemento([by, either, an, 'amino-terminal', acidic, 'domain,', 'R1,', or, an, independent, adjacent, 'domain,', 'R2,', and, may, involve, the, coordinate, action, of, cofactors, '(', 'NF-E2,', 'EKLF,', and, 'Sp1)', which, bind, adjacent, 'cis-elements'])]). relacion([sujeto(['To', directly, assess, mechanisms, of, 'transactivation,', we]), verbo([have]), complemento([developed, an, efficient, 'cell-free', transcription, system, using, recombinant, human, 'GATA-1', '(', 'rhGATA-1)', expressed, in, 'SF9', cells])]). relacion([sujeto(['Factors', from, each, source, were, essentially, equivalent, in, molecular, weight, and, 'DNA']), verbo([binding]), complemento(['properties,', and, highly, similar, in, phosphotryptic, peptide, composition])]). relacion([sujeto(['Notably,', 'DNA']), verbo([binding]), complemento([was, inhibited, following, treatment, with, alkaline, phosphatase])]). relacion([sujeto(['This', work, establishes, an, efficient, in, vitro, system, for, direct, analyses, of, 'mechanisms,', 'cofactors,', and, functional, domains, of, 'GATA-1', which]), verbo([regulate]), complemento([transcription, at, defined, proximal, promoters])]). relacion([sujeto(['The', 'DNA-binding', domain, of, the, erythroid, transcription, factor, 'GATA-1', consists, of, two, closely, 'related,', but, distinct, 'zinc-fingers', which, are, highly]), verbo([conserved]), complemento([among, the, members, of, the, growing, family, of, 'GATA-like', factors])]). relacion([sujeto(['The', 'DNA-binding', domain, of, the, human, 'GATA-1', '(', 'F1F2)', was]), verbo([expressed]), complemento([as, a, 'histidine-tagged', fusion, protein, in, 'Escherichia', coli])]). relacion([sujeto(['F1F2', displayed, 'GATA-1', specific]), verbo([binding]), complemento([activity, toward, its, 'DNA', recognition, sequences, within, the, hypersensitive, site, 3, of, the, human, locus, control, region, and, the, human, 'gamma-globin', promoter])]). relacion([sujeto(['In', contrast, to, 'GATA-1', protein, purified, from, 'K562', 'nuclei,', the, recombinant, 'F1F2']), verbo([bound]), complemento([also, the, 'CCAAT-box', region, of, the, human, 'gamma-globin', promoter])]). relacion([sujeto(['When', the, supplemented, cytokine, was, switched, from, 'GM-CSF', to, 'EPO,', hemoglobin, synthesis, in, 'M-TAT/GM-CSF', cells]), verbo([increased]), complemento([rapidly, '(', within, 5, 'h),', and, the, level, of, 'GATA-1', mRNA, increased])]). relacion([sujeto(['In', 'contrast,', the, addition, of, 'GM-CSF', to, the, 'M-TAT/EPO', cell, culture]), verbo([decreased]), complemento([the, amount, of, 'hemoglobin,', even, in, the, presence, of, 'EPO,', indicating, that, the, 'EPO', signal, for, erythroid, differentiation, is, suppressed, by, 'GM-CSF'])]). relacion([sujeto(['Thus,', erythroid, development, of, 'M-TAT', cells, is]), verbo([promoted]), complemento([by, 'EPO', and, suppressed, by, 'GM-CSF'])]). relacion([sujeto(['These', results, support, the, hypothesis, that, 'EPO', actively, influences, the, programming, of, gene, expression]), verbo([required]), complemento([for, erythroid, progenitor, cell, differentiation])]). relacion([sujeto(['Recently,', we, demonstrated, that, a, 'DNA-binding', 'protein(s)', is]), verbo([involved]), complemento([in, transcriptional, repression, of, the, rat, serine, dehydratase, gene, in, fetal, liver])]). relacion([sujeto(['Here,', we]), verbo([report]), complemento([that, a, 'GAT(A/T)', motif, is, the, target, sequence, for, the, 'DNA-binding', protein])]). relacion([sujeto(['Rat', 'GATA-1']), verbo([expressed]), complemento([as, a, 'GST-fusion', protein, in, 'E'])]). relacion([sujeto([coli]), verbo([bound]), complemento([to, the, 'GAT(A/T)', motif, in, the, serine, dehydratase, gene])]). relacion([sujeto(['Northern', analysis, show, that, 'GATA-1', and, 'GATA-4', mRNAs, are]), verbo([expressed]), complemento([in, fetal, hepatocytes])]). relacion([sujeto(['The', previously, defined, core, fragment, consists, of, 6, footprinted, 'regions,', with, multiple]), verbo([binding]), complemento([sites, for, the, 'erythroid-specific', factor, 'GATA-1', and, 'G-rich', motifs, that, can, interact, with, ubiquitous, factors, such, as, 'Sp1', and, 'TEF-2'])]). relacion([sujeto(['A', fragment, containing, footprints, 1, -, 4, can]), verbo([stimulate]), complemento([transcription, of, a, linked, human, 'beta-globin', gene, to, levels, of, about, 40, '%', of, that, obtained, with, footprints, 1, -, 6])]). relacion([sujeto(['We', further, show, that]), verbo([binding]), complemento([sites, for, the, 'erythroid-specific', factor, 'NF-E2', can, 'co-operatively', interact, with, parts, of, the, 'HS3', core, 'fragment,', and, that, 'HS3', requires, elements, upstream, from, -, 103, in, the, human, 'beta-globin', promoter, for, full, activity])]). relacion([sujeto(['The', transcription, factor, 'GATA-1', is]), verbo([required]), complemento([for, the, normal, development, of, erythroid, cells])]). relacion([sujeto(['GATA-1', is, also]), verbo([expressed]), complemento([in, other, hemopoietic, 'cells,', suggesting, that, it, might, be, initially, activated, in, a, multipotent, progenitor])]). relacion([sujeto(['Epo', dependent, cells]), verbo([express]), complemento(['hemoglobin,', high, levels, of, 'GATA-1,', 'GATA-2', and, 'NF-E2', p45, 'mRNAs,', and, are, positive, for, stem, cell, antigen, 2, '(', 'Sca-2)', and, the, early, myeloid, marker, 'ER-MP12'])]). relacion([sujeto(['IL-3', dependent, cells, can, be, derived, from, 'Epo', dependent, 'lines,', and, are, 'hemoglobin-,', 'Sca-2-', and, 'ER-MP12-negative,']), verbo([have]), complemento([low, 'GATA-1', and, 'NF-E2', p45, mRNA, 'levels,', and, express, myeloid, markers, 'Mac-1,', 'F4/80', and, 'Gr-1'])]). relacion([sujeto(['Brief', treatment, of, 'Epo', dependent, cells, with, myeloid, growth, factors, '(', plus, 'Epo)']), verbo([leads]), complemento([to, the, induction, of, 'Mac-1,', 'F4/80', and, 'Gr-1,', concomitant, with, the, disappearance, from, most, cells, of, 'Sca-2,', 'ER-MP12', and, 'GATA-1', driven, 'T', antigen, nuclear, expression])]). relacion([sujeto(['Thus,', the, immortalized, 'Epo', dependent, cells]), verbo([have]), complemento([the, property, of, a, progenitor, capable, of, differentiation, towards, either, the, erythroid, or, myeloid, lineages])]). relacion([sujeto(['These', cells, initiate, transcription, of, a, proportion, of, 'GATA-1', 'RNA', molecules, at, an, upstream, 'promoter,', previously, known, to, be]), verbo([expressed]), complemento([only, in, testis, cells])]). relacion([sujeto(['We']), verbo([have]), complemento([established, a, hemopoietic, cell, 'line,', 'BL3,', that, possesses, a, rearranged, retroviral, 'genome,', which, we, used, as, a, genetic, tag, for, their, engraftment, into, lethally, irradiated, mice])]). relacion([sujeto(['They']), verbo([express]), complemento(['GATA-1', and, are, able, to, develop, &, 'quot;cobblestones"', with, stromal, cells])]). relacion([sujeto(['They', do, not]), verbo([express]), complemento([and, respond, to, several, hemopoietic, growth, factors, known, to, facilitate, marrow, recovery])]). relacion([sujeto(['However,', they, are, negatively]), verbo([regulated]), complemento([by, 'TGF', beta, and, can, be, stimulated, by, 'mitogen-stimulated', spleen, 'cell-conditioned', medium])]). relacion([sujeto(['The', 'tal-1', 'gene,', which, is, frequently]), verbo([activated]), complemento([in, human, 'T', cell, acute, leukemias, '(', 'T-ALLs),', codes, for, a, protein, of, the, basic, 'helix-loop-helix', family, '(', 'b-HLH)', and, potentially, a, transcription, factor])]). relacion([sujeto(['In', human, and, murine, hematopoiesis, 'tal-1', is]), verbo([expressed]), complemento([during, the, differentiation, of, the, 'erythroid,', megakaryocytic, and, mastocytic, cell, lineages])]). relacion([sujeto(['The', expression, of, 'tal-1', appears, to, be, comodulated, with, that, of, the, transcription, factor, 'GATA-1', 'gene,']), verbo([suggesting]), complemento([that, the, 'GATA-1', protein, may, regulate, the, 'tal-1', gene, activity, in, these, hematopoietic, lineages])]). relacion([sujeto(['To', get, further, insights, into, the, molecular, mechanisms, that, control, 'tal-1', 'expression,', we]), verbo([have]), complemento([isolated, 5, '\'', sequences, of, the, murine, gene, and, compared, them, to, their, human, counterparts])]). relacion([sujeto([gene, segment, -, 122, to, +, 1, ')', contains, two, 'GATA-motifs', '(', at, -, 65, and, -, 33, ')', and, one, 'SP-1', consensus]), verbo([binding]), complemento([site, '(', -, 59, ')'])]). relacion([sujeto(['Mobility', shift, assays, demonstrate, that, 'GATA', proteins, are, able, to]), verbo([interact]), complemento([with, both, 'GATA-motifs', in, a, sequence, specific, 'fashion,', but, with, different, efficiencies])]). relacion([sujeto(['Moreover', transfection, studies, show, that, the, 'GATA-1', protein, directly]), verbo([mediates]), complemento(['tal-1', transcription, by, interacting, with, the, -, 122, /, +, 1, 'fragment,', defined, as, a, minimal, promoter, in, erythroid, cells])]). relacion([sujeto(['Mutagenesis', of, the, promoter, establishes, that, the, -, 33, 'GATA-binding', site, present, in, this, fragment, is, critical, for, 'tal-1', expression, in, erythroid, 'cells,', but, by, itself, does, not]), verbo([lead]), complemento([to, full, promoter, activity])]). relacion([sujeto(['Indeed,', further, mutations, show, that, the, second, -, 65, 'GATA-binding', site, and, the]), verbo([binding]), complemento([motif, for, 'SP1', '(', -, 59, ')', significantly, contribute, to, the, overall, activity, of, the, proximal, 'tal-1', promoter])]). relacion([sujeto(['Altogether,', our, data]), verbo([provide]), complemento([evidence, that, 'GATA-1', cooperates, with, the, transcription, factor, 'SP1', to, mediate, the, 'erythroid-specific', expression, of, the, 'tal-1', gene])]). relacion([sujeto(['To', define, critical, 'cis-acting', elements, that]), verbo([regulate]), complemento([this, 'enhancer,', a, series, of, deletions, from, the, 5, '\'', and, 3, '\'', ends, of, the, 'Bgl', 'II', fragment, were, generated])]). relacion([sujeto(['Both', are]), verbo([required]), complemento([for, full, enhancer, activity])]). relacion([sujeto(['Sequences', identical, to, previously, defined, 'DNA-binding', sites, for, 'SP1', and, 'GATA', are, present, within, 'E1,', and, an, ets]), verbo([binding]), complemento([site, is, located, within, 'E2'])]). relacion([sujeto(['Proteins', that]), verbo([associate]), complemento([with, the, 'IL-4', intronic, 'GATA', and, ets, sites, were, detected, in, mast, cell, nuclear, extracts, by, 'mobility-shift', assays])]). relacion([sujeto([1, exhibit, 'cell-specific', 'expression,']), verbo([suggesting]), complemento([that, these, proteins, play, a, critical, role, in, the, 'lineage-restricted', activity, of, the, 'IL-4', intronic, enhancer, in, mast, cells])]). relacion([sujeto(['In', order, to, elucidate, the, role, of, 'c-myb', gene, in, erythroid, differentiation, of, 'K562', cell]), verbo([induced]), complemento([by, hemin, '(', 'Hm)', and, erythropoietin, '(', 'Epo),', we, constructed, recombinant, plasmid, that, could, produce, antisense, myb, 'RNA', after, induction, with, dexamethasone])]). relacion([sujeto(['During', treatment, with, 'Hm,', 'K562', cells, constitutively]), verbo([expressed]), complemento(['c-myb', 'mRNA,', and, 50, '%', of, them, began, to, synthesize, hemoglobin, '(', 'Hb)'])]). relacion([sujeto(['Expression', of, antisense, myb, 'RNA', reduced, the, amount, of, 'c-myb', 'mRNA,', and, the, percentage, of, 'Hb-synthesizing', cells, was]), verbo([decreased]), complemento([to, 20, '%'])]). relacion([sujeto(['It', is]), verbo([suggested]), complemento([that, constitutive, expression, of, 'c-myb', mRNA, is, necessary, for, 'Hm-induced', 'differentiation,', and, that, a, decrease, in, the, amount, of, 'c-myb', mRNA, induced, by, antisense, myb, 'RNA', expression, suppresses, 'Hm-induced', differentiation])]). relacion([sujeto(['The', amount, of, 'c-myb', mRNA, in, 'K562', cells, was, reduced, during, the, differentiation]), verbo([induced]), complemento([by, 'Epo'])]). relacion([sujeto(['Expression', of, 'GATA-1', mRNA, was, almost, constant, during, 'Hm-induced', 'differentiation,', but]), verbo([increased]), complemento([during, 'Epo', treatment])]). relacion([sujeto(['We']), verbo([have]), complemento([studied, 'GATA-1,', 'GATA-2,', and, stem, cell, leukemia, '(', 'SCL)', gene, expression, in, 30, patients, with, acute, myeloid, leukemia, '(', 'AML)', by, the, reverse, 'transcription-polymerase', chain, reaction, assay])]). relacion([sujeto(['In', 'AML', both, 'GATA-1', and, 'SCL', genes, were, commonly]), verbo([expressed]), complemento([in, 'M6', and, 'M7', 'leukemias,', and, also, in, leukemias, bearing, the, 'platelet-associated', antigen])]). relacion([sujeto(['We']), verbo([found]), complemento([some, 'AML', patients, with, 'GATA-1,', but, not, 'SCL', expression])]). relacion([sujeto(['Our', data]), verbo([suggest]), complemento([that, the, expression, pattern, of, transcription, factors, may, help, to, define, distinct, phenotypes, of, 'AML', cells])]). relacion([sujeto(['GATA-1', is, an, essential, factor, for, the, transcriptional, activation, of, 'erythroid-specific', 'genes,', and, is, also, abundantly]), verbo([expressed]), complemento([in, a, discrete, subset, of, cells, bordering, the, seminiferous, epithelium, in, tubules, of, the, murine, testis])]). relacion([sujeto(['In', examining, normal, and, 'germ-line', defective, mutant, 'mice,', we, show, here, that, 'GATA-1', is]), verbo([expressed]), complemento([only, in, the, 'Sertoli', cell, lineage, in, mouse, testis])]). relacion([sujeto(['GATA-1', expression, in, 'Sertoli', cells, is]), verbo([induced]), complemento([concomitantly, with, the, first, wave, of, 'spermatogenesis,', and, 'GATA-1-positive', cells, are, uniformly, distributed, among, all, tubules, during, prepubertal, testis, development])]). relacion([sujeto(['However,', the, number, of, 'GATA-1-positive', cells, declines, thereafter, and, were]), verbo([found]), complemento([only, in, the, peripheral, zone, of, seminiferous, tubules, in, stages, 'VII,', 'VIII', and, 'IX', of, spermatogenesis, in, the, adult, mouse, testis])]). relacion([sujeto(['In', 'contrast,', virtually, every, 'Sertoli', cell, in, mutant, 'W/Wv,', 'jsd/jsd', or, cryptorchid, mice, '(', all, of, which, lack, significant, numbers, of, germ, 'cells)']), verbo([expresses]), complemento(['GATA-1,', thus, showing, that, the, expression, of, this, transcription, factor, is, negatively, controlled, by, the, maturing, germ, cells])]). relacion([sujeto(['These', observations]), verbo([suggest]), complemento([that, transcription, factor, 'GATA-1', is, a, developmental, 'stage-', and, spermatogenic, 'cycle-specific', regulator, of, gene, expression, in, 'Sertoli', cells])]). relacion([sujeto(['GATA-1', is, a, zinc, finger, 'DNA-binding', protein, thought, to, be]), verbo([involved]), complemento([in, the, expression, of, the, vast, majority, of, erythroid, specific, genes])]). relacion([sujeto(['We']), verbo([have]), complemento([examined, the, phosphorylation, of, 'GATA-1', in, murine, erythroleukemia, '(', 'MEL)', cells, and, have, mapped, the, sites, of, phosphorylation, by, overexpression, of, 'GATA-1', in, monkey, kidney, 'COS', cells])]). relacion([sujeto(['We', show, that, 'GATA-1', is]), verbo([phosphorylated]), complemento([on, 6, serines, within, its, amino, terminus, in, uninduced, 'MEL', cells, and, that, a, 7, th, 'site,', serine, 310, ',', becomes, phosphorylated, after, 'MEL', cells, are, induced, to, differentiate, by, exposure, to, dimethyl, sulfoxide])]). relacion([sujeto(['This', site, lies, near, the, carboxyl, boundary, of, the, 'DNA-binding', domain, in, a]), verbo([conserved]), complemento([region, of, the, protein, believed, to, be, involved, in, 'DNA', bending])]). relacion([sujeto(['Erythroid', 'Kruppel-like', factor, '(', 'EKLF)', is, an, 'erythroid-specific', transcription, factor, that]), verbo([binds]), complemento([a, 'CACCC', motif, found, in, the, human, 'beta-globin', gene, promoter])]). relacion([sujeto(['We']), verbo([have]), complemento([studied, the, promoter, of, the, 'EKLF', gene, and, identified, binding, sites, for, the, transcription, factors, 'GATA-1', and, 'CCAAT-binding', 'Protein', 1, '(', 'CP1)'])]). relacion([sujeto(['We', show, that, both, types, of]), verbo([binding]), complemento([sites, are, required, for, full, 'activity,', and, that, the, 'GATA', motif, at, -, 60, is, essential])]). relacion([sujeto(['The', 'EKLF', promoter, can, be, directly]), verbo([activated]), complemento([in, nonerythroid, cells, in, cotransfection, experiments, by, forced, expression, of, 'GATA-1'])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, 'EKLF', is, dependent, on, 'GATA-1', for, its, expression, and, lies, downstream, 'of,', or, coincident, 'with,', 'GATA-1', in, a, regulatory, hierarchy, in, erythroid, development])]). relacion([sujeto(['Expression', of, the, transcription, factor, 'GATA-1,', which]), verbo([regulates]), complemento([several, erythroid, specific, genes, and, possibly, also, some, megakaryocytic, 'genes,', has, been, previously, detected, in, normal, 'erythroblasts,', 'megakaryocytes,', and, 'basophils,', and, in, some, myeloid, cell, lines])]). relacion([sujeto(['It']), verbo([has]), complemento([been, suggested, that, 'GATA-1', may, be, first, expressed, in, a, common, progenitor, and, then, further, activated, during, 'erythroid-megakaryocytic', and, basophilic, differentiation, and, repressed, during, myeloid, maturation])]). relacion([sujeto(['We']), verbo([found]), complemento(['GATA-1', expression, in, five, of, five, myeloid, and, in, one, megakaryocytic, blast, crisis, of, 'CML,', in, four, of, six, cases, of, myelomonocytic, leukemias, '(', 'M4', according, to, 'FAB', 'classification),', in, one, case, of, erythroleukemia, '(', 'M6),', whereas, lymphoid, blast, crisis, of, 'CML', and, all, other, 'FAB', groups, were, completely, negative])]). relacion([sujeto(['In', 'addition,', a, low, level, of, 'GATA-1', mRNA, was, also]), verbo([expressed]), complemento([by, the, 'GF-D8', cell, line])]). relacion([sujeto(['These', data, further, support, the, hypothesis, that, 'GATA-1', expression, may, occur, not, only, in, erythroid, and, megakaryocytic, 'progenitors,', but, also, in, early, myeloid, 'progenitors,', and, then, be, further]), verbo([regulated]), complemento([during, 'lineage-specific', maturation])]). relacion([sujeto(['This', element, is, localized, 26, kb, upstream, of, the, mouse, embryonic, globin, gene, '(', 'Hba-x)', and, is, highly]), verbo([conserved]), complemento([at, the, protein, binding, sites])]). relacion([sujeto(['However,', three, of, four, 'CACC', boxes, and, one, 'GATA-1']), verbo([binding]), complemento(['site,', identified, in, the, human, 'alpha-LCR,', are, not, conserved, in, the, mouse])]). relacion([sujeto(['Interestingly,', we, identified, a, highly]), verbo([conserved]), complemento([putative, transcription, factor, binding, sequence, '(', 'AAAGG)', that, may, play, an, important, role, in, 'LCR', function])]). relacion([sujeto(['GATA-1']), verbo([binds]), complemento([to, 'WGATAR', consensus, motifs, in, the, regulatory, regions, of, virtually, all, erythroid, 'cell-specific', genes])]). relacion([sujeto(['Analyses', with, cultured, cells, and, 'cell-free', systems]), verbo([have]), complemento([provided, strong, evidence, that, 'GATA-1', is, involved, in, control, of, globin, gene, expression, during, erythroid, differentiation])]). relacion([sujeto(['Targeted', mutagenesis, of, the, 'GATA-1', gene, in, embryonic, stem, cells]), verbo([has]), complemento([demonstrated, its, requirement, in, normal, erythroid, development])]). relacion([sujeto(['Efficient', rescue, of, the, defect]), verbo([requires]), complemento([an, intact, 'GATA', element, in, the, distal, 'promoter,', suggesting, autoregulatory, control, of, 'GATA-1', transcription])]). relacion([sujeto(['To', examine, whether, 'GATA-1', expression]), verbo([involves]), complemento([additional, regulatory, factors, or, is, maintained, entirely, by, an, autoregulatory, 'loop,', we, have, used, a, transient, heterokaryon, system, to, test, the, ability, of, erythroid, factors, to, activate, the, 'GATA-1', gene, in, nonerythroid, nuclei])]). relacion([sujeto(['We', show, here, that, proerythroblasts, and, mature, erythroid, cells, contain, a, diffusible, activity, '(', 'TAG)', capable, of, transcriptional, activation, of, 'GATA-1', and, that, this, activity]), verbo([decreases]), complemento([during, the, terminal, differentiation, of, erythroid, cells])]). relacion([sujeto(['Nuclei', from, 'GATA-1-', mutant, embryonic, stem, cells, can, still, be, reprogrammed, to]), verbo([express]), complemento([their, globin, genes, in, erythroid, 'heterokaryons,', indicating, that, de, novo, induction, of, 'GATA-1', is, not, required, for, globin, gene, activation, following, cell, fusion])]). relacion([sujeto(['The', human, 'beta-globin', 'Locus', 'Control', 'Region', '(', 'LCR)']), verbo([has]), complemento([two, important, activities])]). relacion([sujeto(['Previous', experiments, demonstrated, that, a, 1.9, kb, fragment, containing, the, 5, '\'', 'HS', 2, site]), verbo([confers]), complemento(['position-independent', expression, in, transgenic, mice, and, enhances, human, 'beta-globin', gene, expression, 100, -, fold])]). relacion([sujeto(['Further', analysis, of, this, region, demonstrates, that, multiple, sequences, are]), verbo([required]), complemento([for, maximal, enhancer, 'activity;', deletion, of, 'SP1,', 'NF-E2,', 'GATA-1', or, 'USF', binding, sites, significantly, decrease, 'beta-globin', gene, expression])]). relacion([sujeto(['In', 'contrast,', no, single, site, is]), verbo([required]), complemento([for, 'position-independent', transgene, 'expression;', all, mice, with, 'site-specific', mutations, in, 5, '\'', 'HS', 2, express, human, 'beta-globin', mRNA, regardless, of, the, site, of, transgene, integration])]). relacion([sujeto(['Apparently,', multiple, combinations, of, protein]), verbo([binding]), complemento([sites, in, 5, '\'', 'HS', 2, are, sufficient, to, prevent, chromosomal, position, effects, that, inhibit, transgene, expression])]). relacion([sujeto(['In', order, to]), verbo([gain]), complemento([further, insights, of, the, regulatory, mechanisms, of, human, 'beta-like', globin, gene, switch, during, erythroid, 'development,', we, have, studied, 'protein-DNA', interaction, in, vivo, at, the, human, adult, beta, and, fetal, gamma, globin, promoters, and, their, upstream, 'enhancer,', 5, '\'', 'HS-2,', in, purified, human, adult, 'erythroblasts,', in, which, the, 'beta,', but, not, gamma, or, 'epsilon,', globin, gene, is, actively, transcribing])]). relacion([sujeto(['Protein-DNA']), verbo([binding]), complemento([in, the, beta, globin, 'promoter,', in, particular, at, the, two, 'CACC', promoter, boxes, and, the, 'CCAAT', 'box,', is, detectable, only, in, the, adult, erythroblasts])]). relacion([sujeto(['As', 'expected,', the, gamma, globin, promoters, were]), verbo([bound]), complemento([with, specific, nuclear, factors, in, the, expressing, 'K562', 'cells,', but, not, in, 'non-erythroid', tissues, or, cell, lines])]). relacion([sujeto(['Relatively', weak, protein]), verbo([binding]), complemento([could, also, be, detected, in, the, vicinities, of, the, two, 'CCAAT', boxes, of, the, inactive, gamma, globin, promoters, in, the, adult, erythroblasts])]). relacion([sujeto(['Although', the, patterns, of]), verbo([nuclear]), complemento(['factor-DNA', interaction, in, vivo, at, the, 'NF-E2/AP1,', 'GATA-1,', and, 'GT-I', motifs, of, 5, '\'', 'HS-2', enhancer, in, adult, erythroblasts, are, similar, to, those, in, 'K562', 'cells,', we, have, identified, a, previously, undetected, 'factor-binding', motif, of, 5, '\'', 'HS-2', that, is, protected, only, in, the, adult, erythroblasts])]). relacion([sujeto(['This', motif, is, identical, in, sequence, to, the, 3, '\'', -, 'CACC', box, of, the, human, beta, globin, 'promoter,', and, it, is, well]), verbo([conserved]), complemento([at, the, same, location, among, all, mammalian, 5, '\'', 'HS-2', 'enhancers,', suggesting, an, important, regulatory, role, of, this, element, in, human, beta, globin, gene, transcription, in, adult, erythroblasts])]). relacion([sujeto(['All', of, the, above, four, motifs, of, 5, '\'', 'HS-2', are, free, of]), verbo([nuclear]), complemento([factor, binding, in, 'non-erythroid', 'tissues,', but, two, of, 'them,', 'NF-E2/AP1', and, 'GT-I,', are, bound, with, factors, in, some, 'non-erythroid', cell, lines, but, not, in, others])]). relacion([sujeto(['Among', a, series, of, 5, '\'', flanking, restriction, fragments, linked, to, a, reporter, 'gene,', a, 83, -, bp, fragment, that, includes]), verbo([binding]), complemento([sites, for, the, transcription, factors, 'GATA-1', and, 'Sp-1', gave, low, levels, of, 'erythroid-specific', 'activity,', and, a, 256, -, bp, fragment, that, 'includes,', in, 'addition,', two, sites, for, the, putative, 'CACCC-binding', protein, gave, the, highest, level, of, 'erythroid-specific', transcription])]). relacion([sujeto(['DNase', 'I', footprinting, showed]), verbo([binding]), complemento([of, a, constitutive, factor, to, the, proximal, 'CACCC-binding', 'site,', and, deletion, or, mutation, of, this, site, significantly, reduced, the, overall, expression, while, maintaining, 'tissue-specificity'])]). relacion([sujeto(['A', 0.8, -, kb, restriction, fragment, spanning, the, distal, site]), verbo([caused]), complemento([approximately, a, 'four-fold', rise, in, transcription, from, the, endogenous, or, a, heterologous, promoter, in, 'MEL', cells, independent, of, its, orientation, and, up, to, 1.5, -, fold, rise, in, 'CB-5', 'cells,', but, it, was, inactive, in, 'COS-1', cells, that, were, cotransfected, with, an, expression, plasmid, encoding, 'GATA-1'])]). relacion([sujeto(['These', results, show, that, '(', 1, ')', basal, activity, as, well, as, tissue, specificity, of, the, 'EpoR', promoter, can, be, accounted, for, by, its, interaction, with, 'GATA-1,', and, '(', 2, ')', upstream, sites]), verbo([regulate]), complemento([the, strength, of, the, promoter])]). relacion([sujeto(['Expression', of, the, distal, 'DNase', 'I', hypersensitive, site, and, the, corresponding, enhancer, activity, in, 'MEL', cells]), verbo([suggests]), complemento([a, role, for, this, element, in, 'stage-specific', transcriptional, control])]). relacion([sujeto(['The', recent, development, of, a, whole, panoply, of, multidimensional, 'heteronuclear-edited', and, -, filtered, 'NMR', experiments]), verbo([has]), complemento([revolutionized, the, field, of, protein, structure, determination, by, 'NMR,', making, it, possible, to, extend, the, methodology, from, the, 10, -, kDa, limit, of, conventional, 2, -, dimensional, 'NMR', to, systems, up, to, potentially, 35, -, 40, kDa])]). relacion([sujeto(['The', basic, strategy, for, solving, 3, -, dimensional, structures, of, larger, proteins, and, 'protein-ligand', complexes, in, solution, using, 3, -, and, 4, -, dimensional, 'NMR', spectroscopy, is, 'summarized,', and, the, power, of, these, methods, is, illustrated, using, 3, 'examples:', 'interleukin-1', 'beta,', the, complex, of, calmodulin, with, a]), verbo([target]), complemento(['peptide,', and, the, specific, complex, of, the, transcription, factor, 'GATA-1', with, its, cognate, 'DNA', target, site])]). relacion([sujeto(['All-trans', retinoic, acid, '(', 'RA)', is, an, important, morphogen, in, vertebrate, 'development,', a, normal, constituent, in, human, adult, blood, and, is, also]), verbo([involved]), complemento([in, the, control, of, cell, growth, and, differentiation, in, acute, promyelocytic, leukemia])]). relacion([sujeto(['We']), verbo([have]), complemento([examined, the, effects, of, 'RA', on, normal, hematopoiesis, by, using, early, hematopoietic, progenitor, cells, '(', 'HPC)', stringently, purified, from, adult, peripheral, blood])]). relacion([sujeto(['In', clonogenetic, fetal, calf, 'serum-supplemented', '(', 'FCS+)', or, -, nonsupplemented, '(', 'FCS-)', culture, treated, with, saturating, levels, of, 'interleukin-3', '(', 'IL-3)', 'granulocyte-macrophage', 'colony-stimulating', factor, '(', 'GM-CSF)', and, erythropoietin, '(', 'Ep)', '(', combined, with, 'c-kit', ligand, in, 'FCS(-)-culture', 'conditions),', 'RA']), verbo([induces]), complemento([a, dramatic, 'dose-dependent', shift, from, erythroid, to, granulomonocytic, colony, 'formation,', the, latter, colonies, being, essentially, represented, by, granulocytic, clones])]). relacion([sujeto(['This', shift, is, apparently, not]), verbo([caused]), complemento([by, a, recruitment, 'phenomenon,', because, in, 'FCS+', 'culture,', the, total, number, of, colonies, is, not, significantly, modified, by, 'RA', addition])]). relacion([sujeto(['In', 'FCS-', 'liquid-suspension', culture, supplemented, with, saturating, 'Ep', level, and, 'low-dose', 'IL-3/GM-CSF,', adult, 'HPC', undergo, unilineage, erythropoietic, 'differentiation:', 'Here', 'again,', treatment, with, 'high-dose', 'RA']), verbo([induces]), complemento([a, shift, from, the, erythroid, to, granulocytic, differentiation, pathway])]). relacion([sujeto(['We', then, analyzed, the, expression, of, the, master, 'GATA1', 'gene,', which, encodes, a, finger, transcription, factor]), verbo([required]), complemento([for, normal, erythroid, 'development;', addition, of, 'RA', to, 'HPC', stimulated, into, unilineage, erythropoietic, differentiation, in, liquid, culture, caused, a, virtually, complete, inhibition, of, 'GATA1', mRNA, induction])]). relacion([sujeto(['These', results, indicate, that, 'RA', directly]), verbo([inhibits]), complemento([the, erythroid, differentiation, program, at, the, level, of, early, adult, 'HPC,', and, may, lead, to, a, shift, from, the, erythroid, to, granulocytic, differentiation, pathway])]). relacion([sujeto(['Previous', studies]), verbo([have]), complemento([demonstrated, the, expression, of, 'GATA-1', '(', a, 'DNA-binding', nuclear, 'protein)', in, 'erythrocytes,', 'megakaryocytes,', 'eosinophils,', 'basophils,', mast, 'cells,', early, marrow, progenitor, cells, and, in, mouse, and, human, erythroid, leukaemia, cell, lines])]). relacion([sujeto(['Two']), verbo([conserved]), complemento(['loci,', 'DXHX674h', and, 'DXHX679h,', which, map, to, 'Xp11'])]). relacion([sujeto([21, on, the, human, 'X', chromosome, short, 'arm,']), verbo([have]), complemento([been, positioned, between, the, loci, for, proteolipid, protein, '(', 'Plp)', and, the, 'E1a', subunit, of, pyruvate, dehydrogenase, '(', 'Pdha1)', in, the, distal, region, of, the, mouse, 'X', chromosome, using, 'Mus', musculus, x, 'Mus', spretus, interspecific, backcrosses])]). relacion([sujeto(['These', 'data,', together, with, previous, comparative, mapping, studies, on, another]), verbo([conserved]), complemento([locus, '(', 'DXF34)', and, the, locus, that, encodes, the, erythroid, transcription, factor, '(', 'GATA1),', reveal, that, loci, that, map, to, the, proximal, region, of, the, human, 'X', chromosome, short, arm, lie, in, four, different, regions, of, the, mouse, 'X', chromosome, and, that, the, human, and, mouse, 'X', chromosomes, contain, a, minimum, of, eight, conserved, segments])]). relacion([sujeto(['In', the, case, of, the, 'PF4', 'gene,', this, site]), verbo([has]), complemento([been, shown, to, play, a, critical, role, in, restricting, transcription, to, the, megakaryocyte, lineage])]). relacion([sujeto(['Our', studies, show, that, the, 'TATA-binding', protein, of, 'TFIID', is]), verbo([required]), complemento([for, initiation, of, transcription, from, the, 'GATA', 'box-containing', promoters])]). relacion([sujeto(['GATA-1']), verbo([interacts]), complemento([with, the, core, promoter, 'GATA', motif, and, inhibits, generation, of, preinitiation, complexes])]). relacion([sujeto(['The', functional, significance, of, the, inhibition, of, preinitiation, complexes, is, supported, by, in, vitro, transcription, assays, in, which, transcription, from, the, 'PF4', and, erythropoietin, core, promoters, is]), verbo([suppressed]), complemento([by, 'GATA-1'])]). relacion([sujeto(['We', also, demonstrate, that, 'GATA-2']), verbo([inhibits]), complemento([initiation, of, transcription, from, the, 'PF4', core, promoter])]). relacion([sujeto(['Erythropoietin', '(', 'Epo)', is, a, cytokine, which, specifically]), verbo([regulates]), complemento([differentiation, and, proliferation, of, erythroid, progenitor, cells])]). relacion([sujeto(['We']), verbo([report]), complemento([here, that, 'Epo', receptor, expressed, in, interleukin, 3, -, dependent, lymphoid, 'Ba/F3', cells, transmits, both, differentiation, and, growth, signals])]). relacion([sujeto(['Epo', stimulation, of, these, cells]), verbo([leads]), complemento([to, activation, of, transcription, 'and/or', translation, of, the, 'erythroid-specific', transcription, factors, 'GATA-1', and, 'SCL,', followed, by, the, accumulation, of, both, 'alpha-', and, 'beta-globin', chains])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, expression, and, activation, of, the, 'Epo', receptor, regulates, 'erythroid-specific', gene, expression, and, might, play, a, role, in, determining, a, cell, lineage, in, vivo, and, that, 'GATA-1', and, 'SCL', may, exert, their, effects, after, 'Epo', binds, to, its, receptor])]). relacion([sujeto(['It', was, further]), verbo([found]), complemento([that, chimeric, receptors, composed, of, extracellular, domains, of, 'Epo', receptor, and, cytoplasmic, domains, of, interleukin, 2, or, interleukin, 3, receptors, could, also, induce, 'erythroid-specific', gene, expression, in, 'Ba/F3', cells])]). relacion([sujeto(['The', 'GATA-1', transcription, factor]), verbo([has]), complemento([been, shown, to, be, important, in, the, regulation, of, globin, and, 'non-globin', genes, in, 'erythroid,', megakaryocytic, and, mast, cell, lineages])]). relacion([sujeto(['It', is, a, member, of, a, family, of, 'GATA', proteins, which, both, overlap, in, their, expression, patterns, and]), verbo([bind]), complemento([the, motif, '(', 'A/T)GATA(A/G)'])]). relacion([sujeto(['The', 'GATA', family, of, proteins, are, also, members, of, the, superfamily, of, zinc, 'finger-like', domain, proteins, and]), verbo([have]), complemento([two, similar, domains, of, the, type, 'Cys-X2-Cys-X17-Cys-X2-Cys', which, direct, the, 'DNA', binding, of, the, protein])]). relacion([sujeto(['A', random, oligonucleotide, selection, procedure]), verbo([has]), complemento([been, employed, to, further, elucidate, the, mechanism, of, 'GATA-1-DNA', recognition])]). relacion([sujeto(['The', resulting, oligonucleotides, were, tested, for]), verbo([binding]), complemento([activity, to, both, 'wild-type', and, mutant, 'GATA-1', proteins])]). relacion([sujeto(['Two', classes, of, 'GATA-1-DNA', interaction]), verbo([have]), complemento([been, 'defined,', the, first, requiring, only, the, carboxy, finger, of, 'GATA-1', to, bind, and, having, the, motif, 'GAT(A/T),', the, second, requiring, both, finger, domains, to, bind, and, having, the, core, motif, '(', 'T/C)AAG'])]). relacion([sujeto(['By', using, sequence, comparison, and, depurination, analysis, it, is, concluded, that, the, two, 'finger-like', domains, of, 'GATA-1']), verbo([have]), complemento([different, 'DNA', binding, recognition, motifs])]). relacion([sujeto(['Binding', of, 'GATA-1', to, 'GAT(A/T)', motifs, is]), verbo([associated]), complemento([with, transcriptional, activation, of, linked, genes])]). relacion([sujeto(['The', only, known, '(', 'T/C)AAG', motif, is, in, the, distal, 'CAAT-box', promoter, region, of, the, human, 'A', 'gamma-globin', gene, where, the]), verbo([binding]), complemento([of, 'GATA-1', appears, to, regulate, the, correct, developmental, suppression, of, 'gamma-globin', expression])]). relacion([sujeto(['Four', distinct, factors, in, extracts, from, murine, erythroleukemia, '(', 'MEL)', cells]), verbo([interacted]), complemento([with, the, human, 'beta-globin', gene, promoter, 'CAAT', 'box:', 'CP1,', 'GATA-1,', and, two, novel, 'factors,', denoted, a, and, 'b,', one, of, which, is, highly, inducible, in, the, 'MEL', system])]). relacion([sujeto(['GATA-1']), verbo([binding]), complemento([to, the, 'CAAT', element, was, very, unstable, '(', 'half-life', &, 'lt;', 1, 'min),', whereas, bindings, of, 'a,', 'b,', and, 'CP1', were, comparatively, 'stable,', with, 'half-lives', of, 18, ',', 19, ',', and, 3.5, 'min,', respectively])]). relacion([sujeto(['Stable', transfections, of, 'MEL', cells, showed, that, in, the, presence, of, the, 'beta-globin', locus, control, region, '(', 'LCR),', the, 'wild-type', 'CAAT', 'box,', a, mutant, which]), verbo([bound]), complemento([to, 'GATA-1', with, increased, stability, over, the, normal, 'sequences,', and, a, mutant, which, bound, 'a,', 'b,', and, 'CP1', specifically, could, all, stimulate, transcription, greater, than, ninefold, over, that, induced, by, a, null, 'CAAT', mutation, in, both, uninduced, and, terminally, differentiated, 'MEL', cells])]). relacion([sujeto(['A', mutant, which]), verbo([bound]), complemento([the, a, and, b, factors, specifically, gave, only, a, twofold, stimulation, of, promoter, 'activity,', and, this, lower, activity, correlated, with, a, decrease, in, the, stability, of, binding, of, the, b, protein])]). relacion([sujeto(['On', the, other, 'hand,', 'CP1']), verbo([binding]), complemento([alone, did, not, stimulate, transcription])]). relacion([sujeto(['Taken', 'together,', these, results]), verbo([suggest]), complemento([that, in, the, context, of, the, 'wild-type', 'beta-globin', 'CAAT', element, the, b, factor, stimulates, transcription, directed, by, the, 'LCR', in, 'MEL', 'cells,', although, the, 'LCR', can, also, function, through, more, stable, 'GATA-1-binding', sequences])]). relacion([sujeto(['However,', in, 'K562', 'cells,', the, 'wild-type', 'beta-globin', 'CAAT', box, alone, was, unable, to]), verbo([stimulate]), complemento([gene, expression, directed, by, the, 'LCR', and, high, levels, of, transcription, were, obtained, only, upon, inclusion, of, more, upstream, 'beta-globin', promoter, sequences])]). relacion([sujeto(['We']), verbo([have]), complemento([previously, shown, that, a, fragment, extending, 643, base, pairs, upstream, the, transcription, start, site, of, the, human, 'GPIIb', promoter, was, able, to, control, the, 'tissue-specific', expression, of, the, 'CAT', gene, in, transfection, experiments])]). relacion([sujeto(['Gel', shift, analysis, revealed, that]), verbo([nuclear]), complemento([extracts, from, the, erythroleukemic, cell, line, 'HEL', contain, a, 'DNA-binding', protein, that, recognizes, these, 'GATA', sites])]). relacion([sujeto(['Using', an, antiserum, raised, to, an, hydrophilic, region, of, the, transcription, factor, 'GATA-1,', the, 'HEL', 'GATA-binding', protein, was]), verbo([found]), complemento([to, be, 'GATA-1'])]). relacion([sujeto(['The', -, 463, 'GATA', motif, located, in, an, enhancer, region, is, essential, for, full, transcription, activity, and, was]), verbo([found]), complemento([to, be, dominant, upon, the, other, 'GATA', motifs])]). relacion([sujeto(['The', use, of, recombinant, 'adeno-associated', virus, '(', 'rAAV)', vectors]), verbo([provides]), complemento([a, new, strategy, to, investigate, the, role, of, specific, regulatory, elements, and, 'trans-acting', factors, in, globin, gene, expression])]). relacion([sujeto(['The', vector, also, contains, the, phosphotransferase, gene, that]), verbo([confers]), complemento([resistance, to, neomycin, '(', 'NeoR)'])]). relacion([sujeto(['HS2', region, mutations, within, the, 'NF-E2', motifs]), verbo([prevented]), complemento(['NF-E2', binding, while, preserving, 'AP-1', binding])]). relacion([sujeto(['Another', set, in, the, 'GATA-1', motif]), verbo([prevented]), complemento([binding, of, the, factor])]). relacion([sujeto(['In', uninduced, 'K562', 'cells,', 'mut-NFE2', clones]), verbo([expressed]), complemento(['A', 'gamma*', mRNA, at, the, same, level, as, the, 'WT', 'clones,', compared, with, a, lack, of, 'A', 'gamma*', signal, in, the, '(', -, ')', 'HS2', clones])]). relacion([sujeto(['However,', hemin, induction, of, 'mut-NFE2', clones, did, not, result, in, an]), verbo([increase]), complemento([in, the, 'A', 'gamma*', signal, above, the, level, seen, in, uninduced, cells])]). relacion([sujeto(['Mut-GATA1', clones]), verbo([expressed]), complemento([the, 'A', 'gamma*', mRNA, at, the, same, level, as, 'WT', clones, in, both, uninduced, and, induced, cells])]). relacion([sujeto(['Thus,', 'GATA-1']), verbo([binding]), complemento([to, this, site, does, not, appear, to, be, required, for, the, enhancing, function, of, 'HS2', in, this, context])]). relacion([sujeto(['In', the, present, work, we]), verbo([have]), complemento([studied, the, kinetics, of, its, expression, and, activity, during, development, of, normal, human, erythroid, 'progenitors,', grown, in, primary, cultures])]). relacion([sujeto(['The']), verbo([binding]), complemento([activity, of, the, ubiquitous, factor, 'SP1', showed, a, biphasic, 'pattern;', its, second, peak, usually, coincided, with, the, 'GATA-1', 'peak,', suggesting, that, 'SP1', also, plays, a, specific, role, in, erythroid, maturation])]). relacion([sujeto(['The', highest, activity, of, 'GATA-1', per, erythroid, cell, was]), verbo([found]), complemento([on, day, 6, -, 8, ',', immediately, preceding, the, major, rise, in, globin, gene, mRNA, and, in, the, number, of, hemoglobinized, cells])]). relacion([sujeto(['The', results, imply, that, a, high, level, of, 'GATA-1', activity, is, necessary, for, globin, gene, expression, and, erythroid, 'maturation,']), verbo([suggesting]), complemento([that, a, requirement, for, a, threshold, concentration, of, 'GATA-1', is, part, of, the, mechanism, that, determines, the, final, steps, of, erythroid, maturation])]). relacion([sujeto(['Although', the, formation, of, terminally, differentiated, erythroid, cells]), verbo([has]), complemento([been, shown, to, require, the, presence, of, a, functional, 'GATA-1', gene, in, 'vivo,', the, role, of, this, transcription, factor, and, other, members, of, the, 'GATA', family, at, earlier, stages, of, erythroid, differentiation, is, unclear])]). relacion([sujeto(['In', this, 'report,', the, expression, of, 'GATA-1,', 'GATA-2,', and, 'GATA-3']), verbo([has]), complemento([been, examined, in, enriched, peripheral, blood, progenitors, before, and, after, culture, in, a, 'well-characterized', liquid, culture, system])]). relacion([sujeto(['Erythroleukemic', cell, lines]), verbo([express]), complemento([little, or, no, 'GATA-3,', but, high, levels, of, 'GATA-1', and, 'GATA-2'])]). relacion([sujeto(['When', they, are]), verbo([induced]), complemento([to, display, the, terminal, erythroid, 'phenotype,', little, change, in, the, level, of, 'GATA-1', is, detected, but, a, significant, decline, in, the, levels, of, 'GATA-2', is, observed, commensurate, with, the, degree, of, maturation, achieved, by, the, cells])]). relacion([sujeto(['Enrichment', of, erythroid, progenitors, from, peripheral, blood]), verbo([leads]), complemento([to, selection, of, cells, that, express, both, 'GATA-1', and, 'GATA-2'])]). relacion([sujeto(['These', results, indicate, that, 'GATA-1', upregulation, is]), verbo([associated]), complemento([with, both, the, initiation, and, the, maintenance, of, the, erythroid, 'program,', but, that, these, two, processes, appear, to, be, under, separate, regulatory, control])]). relacion([sujeto(['Thus,', the, dynamic, changes, in, the, levels, of, different, 'GATA', factors, that, occur, during, primary, erythroid, differentiation]), verbo([suggest]), complemento([that, the, levels, of, these, factors, may, influence, the, progression, to, specific, hematopoietic, pathways])]). relacion([sujeto(['Inappropriate', expression, of, the, 'Evi-1', 'zinc-finger', gene, in, hematopoietic, cells]), verbo([has]), complemento([been, associated, with, acute, myelogenous, leukemia, and, myelodysplastic, syndromes, in, murine, models, and, in, humans])]). relacion([sujeto(['Consistent', with, 'this,', previous, studies]), verbo([have]), complemento([shown, that, aberrant, expression, of, the, 'Evi-1', gene, in, a, myeloid, progenitor, cell, line, blocks, granulocytic, differentiation])]). relacion([sujeto(['Erythroid', differentiation]), verbo([has]), complemento([been, shown, to, require, the, 'GATA-1', transcription, factor, that, binds, to, a, sequence, contained, within, the, consensus, binding, sequence, identified, for, 'Evi-1'])]). relacion([sujeto(['Together', the, data, support, the, hypothesis, that, inappropriate, expression, of, the, 'Evi-1', gene, blocks, erythropoiesis, by, repressing, the, transcription, of, a, subset, of, 'GATA-1']), verbo([target]), complemento([genes])]). relacion([sujeto(['Ets', family, proteins]), verbo([activate]), complemento([transcription, via, binding, to, the, 'GGAA', core, sequence, located, in, the, 'promoter/enhancer', elements, of, many, cellular, and, viral, genes])]). relacion([sujeto(['The', promoter, of, the, chicken, 'GATA-1', gene, contains, multiple, ets]), verbo([binding]), complemento([sites, '(', 'EBS),', two, of, them, are, present, in, palindromic, form])]). relacion([sujeto(['The', 'GATA-1', promoter]), verbo([has]), complemento([been, shown, to, be, activated, by, the, 'E26', virus])]). relacion([sujeto(['In', this, 'study,', we]), verbo([have]), complemento([analysed, whether, the, palidromic, 'EBS', of, the, chicken, 'GATA-1', promoter, is, a, target, for, binding, and, activation, by, members, of, the, cellular, ets, gene, family, products])]). relacion([sujeto(['The', results, herein, indicate, that, both, 'EBS', in, the, palindrome, are]), verbo([required]), complemento([for, 'DNA-binding', because, mutations, in, either, site, reduces, the, activity, by, at, least, 95, '%'])]). relacion([sujeto(['Moreover,', 'DNA']), verbo([binding]), complemento([of, 'ETS1', to, the, 'EBS', palindrome, is, dramatically, stabilized, in, the, presence, of, a, specific, monoclonal, antibody, whose, epitope, maps, between, amino, acid, positions, 240, -, 260])]). relacion([sujeto(['Although', each, of, the, single, sites, 'bind,', the, efficiency, of]), verbo([binding]), complemento([is, extremely, low])]). relacion([sujeto(['Furthermore,', for, efficient]), verbo([binding]), complemento([the, two, sites, must, be, in, an, inverted, configuration, because, of, the, fact, that, the, oligonucleotide, containing, the, left, and, right, 'EBS', in, the, same, orientation, binds, 10, -, fold, less, than, the, oligonucleotide, containing, the, 'EBS', palindrome])]). relacion([sujeto(['Additionally,', we, show, that, the, transcription, of, a, reporter, gene, '(', 'CAT)', either, linked, to, the, 'GATA-1', 'EBS', palindrome, or, 'GATA-1', promoter, can, be]), verbo([activated]), complemento([by, cotransfection, with, 'ETS1,', 'alternatively-spliced', 'ETS1,', 'ETS2', or, 'ERGB/Hu-FLI-1', expression, vectors])]). relacion([sujeto(['Erythroid', differentiation]), verbo([involves]), complemento([the, activation, of, a, number, of, 'erythroid-specific', 'genes,', most, of, 'which,', including, the, globin, genes, and, the, erythropoietin, receptor, '(', 'Epo-R)', 'gene,', 'are,', at, least, in, 'part,', regulated, by, the, transcription, factor, 'GATA-1'])]). relacion([sujeto(['The', results, were, compared, to, those, obtained, with, the, parental, 'granulocyte-macrophage', 'colony-stimulating', factor, '(', 'GM-CSF)-dependent', cell, 'line,', 'UT-7,', which]), verbo([has]), complemento([a, predominantly, megakaryoblastic, phenotype, and, is, unable, to, proliferate, continuously, in, the, presence, of, 'Epo'])]). relacion([sujeto(['UT-7', 'Epo', and, 'UT-7']), verbo([expressed]), complemento([similar, levels, of, 'GATA-1', mRNA, and, binding, activity])]). relacion([sujeto(['The', two, lines, also]), verbo([expressed]), complemento([comparable, levels, of, 'Epo-R', mRNA, while, the, number, of, 'Epo-binding', sites, on, 'UT-7', 'Epo', cells, was, 'one-sixth', the, number, of, 'UT-7', cells, '(', 2400, +, /, -, 3, vs])]). relacion([sujeto(['This', difference, in, the, number, of]), verbo([binding]), complemento([sites, could, be, due, to, differences, in, cell, surface, '(', 'UT-7', cells, are, 20, '%', smaller, than, the, parental, 'UT-7', 'cells)', or, in, receptor, turnover])]). relacion([sujeto(['By', 'Northern', 'analysis,', 'UT-7', cells]), verbo([expressed]), complemento([detectable, levels, of, 'beta-', and, 'gamma-globin', but, not, 'alpha-globin'])]). relacion([sujeto(['In', 'comparison,', 'UT-7', 'Epo', cells]), verbo([expressed]), complemento(['alpha-globin', and, higher, levels, of, 'gamma-globin', '(', 5, -, 'fold)', and, 'beta-globin', '(', from, barely, to, clearly, 'detectable)'])]). relacion([sujeto(['The', frequency, of, the, cells, which]), verbo([expressed]), complemento(['beta-', and, 'gamma-globin', genes, in, the, two, cell, populations, was, measured, by, immunofluorescence, with, 'beta-', and, 'gamma-specific', antibodies])]). relacion([sujeto(['The', number, of, 'gamma-positive', cells, and, their, fluorescence, intensity, were, higher, in, 'UT-7', 'Epo', than, in, 'UT-7', cells, '(', 0, to, 17, '%', barely, positive, cells, and, 23, to, 40, '%', clearly, positive, 'cells,', 'respectively),', indicating, that, the]), verbo([increase]), complemento([in, globin, mRNA, observed, in, 'UT-7', 'Epo', is, due, to, both, an, increase, of, gene, expression, per, cell, and, an, increase, in, numbers, of, cells, containing, 'gamma-globin'])]). relacion([sujeto(['The', levels, of, 'GATA-1,', 'Epo-R', and, globin, mRNA]), verbo([expressed]), complemento([were, not, affected, by, a, 24, -, hour, incubation, of, either, cell, line, with, 'Epo,', 'GM-CSF', or, 'interleukin-3', '(', 'IL-3)'])]). relacion([sujeto(['(', 'ABSTRACT', 'TRUNCATED', 'AT', 400, 'WORDS)', 'Treatment', of, mouse, erythroleukemia, '(', 'MEL)', cells, with, hexamethylene, bisacetamide]), verbo([induces]), complemento([a, program, of, 'erythrodifferentiation,', as, judged, by, an, increase, in, the, synthesis, of, globins, and, other, 'erythroid-specific', products])]). relacion([sujeto(['This', induction, can, be]), verbo([inhibited]), complemento([by, 'glucocorticoids,', e])]). relacion([sujeto(['GATA-1', is, highly]), verbo([expressed]), complemento([in, erythroid, 'cells,', including, 'MEL', cells])]). relacion([sujeto(['We', noted, a, glucocorticoid, receptor, '(', 'GR)', response, element, motif, near, a, 'GATA-RE', motif, in, the, promoter, region, of, the, mouse, 'beta-major', and, 'beta-minor', globin, genes, and, about, 130, bases, away, from, a, 'GATA-RE', in, the, alpha, 1, -, globin, gene, promoter, 'and,', 'therefore,', investigated, the, possibility, that, the, 'dexamethasone-induced', inhibition, of]), verbo([induced]), complemento(['MEL', cell, differentiation, may, involve, effects, of, the, 'GR', on, 'GATA-1', activity])]). relacion([sujeto(['Evidence', obtained, from, transfection, assays, and, 'DNA', electrophoretic, mobility, shift, assays, indicates, that, the, 'GR']), verbo([binds]), complemento(['GATA-1', and, interferes, with, its, function, before, any, interaction, with, 'DNA,', but, that, the, presence, of, a, glucocorticoid, response, element, near, a, 'GATA-RE', augments, the, 'GR', effect])]). relacion([sujeto(['The', 'N-terminal', 106, -, amino, acid, domain, of, the, 'GR', was]), verbo([found]), complemento([to, be, essential, for, the, 'effect,', possibly, by, binding, to, 'GATA-1'])]). relacion([sujeto([it]), verbo([has]), complemento([been, shown, by, others, to, bind, to, its, own, promoter, and, 'up-regulate', its, own, 'transcription,', the, finding, that, activated, 'GR', can, interfere, with, 'GATA-1', function, may, provide, an, explanation, for, the, inhibition, by, glucocorticoids, of, the, entire, program, of, erythroid, differentiation, in, 'MEL', cells])]). relacion([sujeto(['That', 'is,', by, interfering, with, 'GATA-1', 'function,', the, 'GR']), verbo([inhibits]), complemento([not, only, the, expression, of, erythroid, structural, 'genes,', but, may, also, inhibit, the, expression, of, a, primary, erythroid, regulatory, 'gene,', 'GATA-1'])]). relacion([sujeto(['It', was, also, shown, that, the, 'GATA-RE', in, each, of, the, 'beta-globin', promoters]), verbo([responds]), complemento([to, mouse, 'GATA-1', in, a, functional, transfection, assay])]). relacion([sujeto(['The', 'sequence-specific', 'DNA-binding', protein, factor, 'F6,', which]), verbo([binds]), complemento([upstream, of, the, cluster, of, the, chicken, 'alpha-globin', 'genes,', has, previously, been, found, to, interact, with, a, 'DNA', fragment, containing, a, replication, origin, and, a, nuclear, matrix, binding, site])]). relacion([sujeto(['This', protein]), verbo([has]), complemento([been, partially, characterized])]). relacion([sujeto(['Based', on, its, molecular, weight, and]), verbo([binding]), complemento(['affinity,', 'F6', belongs, to, a, family, of, 'GATA', 'proteins,', the, chicken, equivalent, of, transcription, factor, 'NFE-1'])]). relacion([sujeto(['An', oligonucleotide, including, the]), verbo([binding]), complemento([site, for, 'F6', competes, for, binding, of, the, 'above-mentioned', 'DNA', fragment, to, the, nuclear, matrix])]). relacion([sujeto(['This', indicates, an, involvement, of, this, protein, in, the, interaction, between, 'DNA', and, the]), verbo([nuclear]), complemento([matrix])]). relacion([sujeto(['The', transcription, factor, 'GATA-1', is, a, fundamental, regulator, of, genes, in, haematopoietic, cell, lineages, and, belongs, to, a, family, of, factors, that]), verbo([bind]), complemento([to, the, consensus, sequence, 'WGATAR'])]). relacion([sujeto(['The', 'GATA', motif, was, originally, identified, in, 'cis-regulatory', regions, of, globin, and, other, 'erythroid-specific', 'genes,', but, the, range, of, genes, controlled, by, the, 'GATA', factors]), verbo([has]), complemento([since, expanded])]). relacion([sujeto(['Members', of, the, 'GATA', transcription, factor, family, share, a]), verbo([conserved]), complemento(['zinc-finger', 'DNA-binding', 'domain,', but, the, expression, profile, of, each, 'GATA', factor, is, distinct])]). relacion([sujeto(['Here', we, show, that, a, testis, form, of, murine, '(', 'm)GATA-1', messenger, 'RNA', is]), verbo([transcribed]), complemento([from, a, promoter, located, 5, '\'', to, the, erythroid, first, 'exon,', and, the, remaining, exons, '(', which, encode, the, 'mGATA-1', 'protein)', are, used, in, common, by, both, testis, and, erythroid, transcripts])]). relacion([sujeto(['We', use, an, 'anti-mGATA-1', monoclonal, antibody, to, show, that, the, factor]), verbo([expressed]), complemento([in, erythroid, cells, is, the, same, as, that, found, in, the, seminiferous, tubules, of, murine, testis])]). relacion([sujeto(['The', 'GATA-1-expressing', cells, in, 10, -, 'week-old', testis, were]), verbo([found]), complemento([only, in, contact, with, the, basement, membrane, of, seminiferous, 'tubules,', suggesting, that, 'GATA-1', regulates, genes, during, the, earliest, stages, of, spermatogenesis])]). relacion([sujeto(['Although', sequences, located, between, -, 559, and, -, 88, of, the, zeta, 2, globin, gene, were, dispensable, for, its, expression, on, enhancerless, 'plasmids,', they, were]), verbo([required]), complemento([for, the, 'HS-40', 'enhancer-mediated', activity, of, the, zeta, 2, globin, promoter])]). relacion([sujeto(['Site-directed', mutagenesis, demonstrated, that, this, 'HS-40', 'enhancer-zeta', 2, globin, promoter, interaction, is]), verbo([mediated]), complemento([by, the, two, 'GATA-1', factor, binding, motifs, located, at, -, 230, and, -, 104, ',', respectively])]). relacion([sujeto(['Bal', 31, deletion, mapping, data]), verbo([suggested]), complemento([that, one, 'GATA-1', 'motif,', one, 'GT', 'motif,', and, two, 'NF-E2/AP1', motifs, together, formed, the, functional, core, of, 'HS-40', in, the, 'erythroid-specific', activation, of, the, zeta, 2, globin, promoter])]). relacion([sujeto(['Site-directed', mutagenesis, further, demonstrated, that, the, enhancer, function, of, one, of, the, two, 'NF-E2/AP1', motifs, of, 'HS-40', is]), verbo([mediated]), complemento([through, its, binding, to, 'NF-E2', but, not, 'AP1', transcription, factor])]). relacion([sujeto(['All', sequence, motifs, within, the, functional, core, of, 'HS-40,', as, mapped, by, transient, expression, 'analysis,', appeared, to]), verbo([bind]), complemento([a, nuclear, 'factor(s)', in, living, 'K562', cells, but, not, in, nonerythroid, cells])]). relacion([sujeto(['On', the, other, 'hand,', only, one, of, the, apparently, nonfunctional, sequence, motifs, was]), verbo([bound]), complemento([with, factors, in, vivo])]). relacion([sujeto(['In', comparison, to, 'K562,', nucleated, erythroblasts, from, adult, human, bone, marrow, exhibited, a, similar, but, nonidentical, pattern, of]), verbo([nuclear]), complemento([factor, binding, in, vivo, at, the, 'HS-40', region])]). relacion([sujeto(['These', data]), verbo([suggest]), complemento([that, transcriptional, activation, of, human, embryonic, zeta, 2, globin, gene, and, the, 'fetal/adult', alpha, globin, genes, is, mediated, by, erythroid, 'cell-specific', and, developmental, 'stage-specific', nuclear, 'factor-DNA', complexes, which, form, at, the, enhancer, '(', 'HS-40)', and, the, globin, promoters])]). relacion([sujeto(['We']), verbo([report]), complemento([the, characterization, of, the, 'cis-', and, 'trans-acting', elements, involved, in, the, 'tissue-specific', activity, of, the, 'L', gene, erythroid, promoter])]). relacion([sujeto(['A', 'R-PK', 'DNA', fragment, extending, from, -, 870, to, +, 54, relative, to, the, cap, site]), verbo([confers]), complemento([erythroid, specificity, to, a, reporter, gene])]). relacion([sujeto(['Within', this, 'region,', we, define, a, minimal, promoter, '(', -, 62, to, +, 54, ')', that, displays, 'erythroid-specific', activity, and, contains, two, 'DNA']), verbo([binding]), complemento([sites])]). relacion([sujeto(['One,', located, at, -, 50, ',']), verbo([binds]), complemento([members, of, the, 'CCACC/Sp1', family, and, the, 'other,', located, at, -, 20, ',', binds, the, erythroid, factor, 'GATA-1'])]). relacion([sujeto(['Although', the, -, 20, 'GATA']), verbo([binding]), complemento([site, '(', 'AGATAA)', is, also, a, potential, 'TFIID', binding, 'site,', it, does, not, bind, 'TFIID'])]). relacion([sujeto(['Furthermore,', the, substitution, of, this, 'GATA']), verbo([binding]), complemento([site, by, a, canonical, 'TFIID', binding, site, suppresses, the, promoter, activity])]). relacion([sujeto(['Mutations', and, deletions, of, both, sites, indicate, that, only, the, association, of, 'CCACC/Sp1', and, 'GATA']), verbo([binding]), complemento([sites, can, drive, efficient, and, 'tissue-specific', expression, of, this, 'R-PK', minimal, promoter])]). relacion([sujeto(['Finally,', by, 'co-transfection', 'experiments,', we, study, the, elements]), verbo([involved]), complemento([in, the, 'hGATA-1', transactivation, of, the, 'R-PK', promoter, in, 'HeLa', cells])]). relacion([sujeto(['Previous', studies]), verbo([have]), complemento([shown, that, a, -, 112, to, +, 78, 'DNA', fragment, from, the, erythroid, promoter, of, the, human, porphobilinogen, deaminase, '(', 'PBGD)', gene, has, 'erythroid-specific', activity])]). relacion([sujeto(['This', 'PBGD-(-112', to, +, 78, ')', promoter, contains, a, 'CCACC']), verbo([binding]), complemento([site, '(', position, -, 100, ')', ',', a, 'GATA', binding, site, '(', position, -, 70, ')', and, an, initiator, element, around, the, cap, site])]). relacion([sujeto(['Using', a, cotransfection, 'assay,', we]), verbo([find]), complemento([that, the, human, factor, 'GATA-1', 'trans-activates', the, 'PBGD-(-112', to, +, 78, ')', promoter, in, 'non-erythroid', cells])]). relacion([sujeto(['We', show, 'that,', if, 'trans-activation', is, abolished, by, mutations, that, destroy, either, the, -, 100, 'CCACC']), verbo([binding]), complemento([or, the, -, 70, 'GATA', binding, 'sites,', replacement, of, the, -, 100, 'CCACC', binding, site, by, a, 'simian-virus-40-protein-1', '(', 'Sp1)', binding, site, maintains, both, the, 'erythroid-specific', activity, of, this, promoter, and, the, human, 'GATA-1', 'trans-activation'])]). relacion([sujeto(['Thus,', human, 'GATA-1']), verbo([acts]), complemento([on, the, 'PBGD', promoter, in, association, with, 'Sp1', or, 'CCACC', binding, proteins])]). relacion([sujeto(['This', 'PBGD-(-112', to, +, 78, ')', promoter, is]), verbo([activated]), complemento([20, -, fold, by, a, 'cis-linked', 5, '\'', hypersensitive, site, 2, '(', 5, '\'', 'HS-2)', of, the, human, 'beta-globin', locus, control, region])]). relacion([sujeto(['This', activation, depends, on, the, -, 70, 'GATA', and, -, 100, 'CCACC', or, 'Sp1']), verbo([binding]), complemento([sites])]). relacion([sujeto(['Thus,', the, -, 100, 'CCACC']), verbo([binding]), complemento([site, is, indispensable, for, the, correct, activity, and, sensitivity, of, the, human, 'PBGD', promoter, to, the, 5, '\'', 'HS-2', 'enhancer,', whereas, the, -, 70, 'GATA', binding, site, can, functionally, be, replaced, by, upstream, 'cis-acting', elements])]). relacion([sujeto(['Recently,', many, investigators]), verbo([have]), complemento([been, interested, in, the, study, on, eosinophil, biology, since, genes, association, with, eosinophils, such, as, 'interleukin-5', or, eosinophil, granule, proteins, '(', 'EPO,', 'ECP,', 'EDN,', 'MBP,', and, 'CLC),', were, isolated])]). relacion([sujeto(['However,', the, molecular, basis, for, the, commitment, of, progenitors, to, the, eosinophil, lineage]), verbo([has]), complemento([not, been, determined])]). relacion([sujeto(['ECP,', 'EDN,', 'EPO,', 'MBP,', and, 'CLC)', are]), verbo([expressed]), complemento([and, regulated, during, eosinophilopoiesis, is, also, unknown])]). relacion([sujeto(['In', this, 'paper,', 'I', described, the, characterization, of, genes, encoding, eosinophil, granule, proteins, and, the, mRNA, expression, of, 'GATA-1']), verbo([binding]), complemento([transcription, factor, during, eosinophil, differentiation])]). relacion([sujeto(['We']), verbo([have]), complemento([analysed, a, small, region, of, the, 'LCR', '(', 'HS3)', in, transgenic, animals, to, determine, the, minimal, interactions, that, are, required, for, this, property])]). relacion([sujeto(['The', results, show, that, a, specific, combination, of, a, 'G-rich', sequence, flanked, on, each, side, by, one]), verbo([binding]), complemento([site, for, the, transcription, factor, 'GATA1', is, essential, to, obtain, 'position-independent', expression, of, a, linked, beta, globin, gene, in, erythroid, cells])]). relacion([sujeto(['The', overall, transcriptional, activity, of, 'HS3', is, achieved, through, synergy, with, other, combinations, of, similar]), verbo([binding]), complemento([sites])]). relacion([sujeto(['Anthracycline', antitumor, 'drugs,', particularly, aclacinomycin, '(', 'ACM)']), verbo([have]), complemento([been, shown, to, be, potent, inducers, of, erythroid, differentiation, in, human, leukemic, 'K562', cells])]). relacion([sujeto(['Here', we]), verbo([report]), complemento([that, such, an, event, is, associated, with, an, overexpression, of, the, 'erythroid-specific', transcription, factors, 'GATA-1', and, 'NFE-2'])]). relacion([sujeto(['Using', the, electrophoretic, mobility, shift, 'assay,', during, differentiation, over, 3, days, of, 'culture,', we]), verbo([have]), complemento([observed, an, increase, in, the, binding, either, of, 'GATA-1', to, the, promoter, of, the, 'gamma-globin', gene, '(', region, -, 201, to, -, 156, ')', or, 'NFE-2', to, the, promotor, of, the, porphobilinogen, deaminase, gene, '(', region, -, 170, to, -, 142, ')'])]). relacion([sujeto(['Enhanced']), verbo([binding]), complemento([capacity, of, 'GATA-1', was, confirmed, by, an, increase, in, its, mRNAs])]). relacion([sujeto(['Moreover,', 'GATA-1', and, 'NFE-2', overexpression]), verbo([has]), complemento([been, shown, to, be, specific, of, the, differentiating, effect, of, the, drug, and, not, of, its, growth, inhibitory, effect])]). relacion([sujeto(['In', 'contrast,', no, change, was, observed, in, the]), verbo([binding]), complemento([of, the, ubiquitous, factors, 'OTF-1', and, 'AP-1,', except, on, day, 3, ',', where, 'AP-1', decreased])]). relacion([sujeto(['Although', 'ACM', is, a, 'DNA-intercalating', 'agent,', it, did, not, directly, affect, transcription, factors]), verbo([binding]), complemento([to, their, 'cis-sequences', as, assessed, by, the, preincubation, of, the, oligonucleotides, probes, with, increasing, concentrations, of, 'ACM'])]). relacion([sujeto(['Taken', 'together,', these, results, strongly]), verbo([suggest]), complemento([that, 'ACM', could, exert, their, 'erythroid-differentiating', activity, by, modulating, the, expression, of, transcription, factors, which, specifically, regulate, the, transcription, of, erythroid, genes])]). relacion([sujeto(['Erythroid', differentiation]), verbo([leads]), complemento([to, the, production, of, red, blood, cells, that, contain, a, high, level, of, hemoglobin])]). relacion([sujeto(['This', level, is, mainly]), verbo([regulated]), complemento([by, globin, gene, transcription, during, development, and, differentiation])]). relacion([sujeto(['Although', numerous, 'cis-acting', sequences, are]), verbo([involved]), complemento([in, transcriptional, activity, of, globin, 'genes,', combinations, of, three, 'motifs,', 'CCACC,', 'SP1', and, 'GATA', represent, the, core, elements, of, their, regulatory, sequences])]). relacion([sujeto(['These', combinations, are, also]), verbo([found]), complemento([in, promoters, 'and/or', enhancers, of, 'non-globin', genes, specifically, expressed, in, the, late, stages, of, erythroid, differentiation])]). relacion([sujeto(['The', 'CCACC', and, 'SP1', sequences]), verbo([bind]), complemento([proteins, that, do, not, display, erythrocytic, 'specificity,', and, the, 'GATA', sequences, bind, a, family, of, transacting, factors, recently, cloned])]). relacion([sujeto(['The', 'GATA', family, members, are, distinctive, for, a, highly, homologous, 'DNA']), verbo([binding]), complemento([domain, that, exists, in, two, zinc, fingers, reminiscent, of, those, of, the, glucocorticoid, receptor])]). relacion([sujeto(['The', 'GATA/SP1', and, 'GATA/CCACC', associations, are, present, in, 'positive,', negative, or, inducible, regulatory, sequences]), verbo([suggesting]), complemento([that, other, elements, control, the, fine, tuning, of, erythroid, gene, expression])]). relacion([sujeto(['NF-E2,', which, is, a, major, transcriptional, 'activator,', members, of, the, ets, family, which, are, implicated, in, the, early, stages, of, erythropoiesis, and, finally, 'c-erbA', which, directly]), verbo([regulates]), complemento([a, set, of, 'erythroid-specific', genes, are, proteins, that, bind, these, latter, regulatory, motifs])]). relacion([sujeto(['We']), verbo([have]), complemento([used, 'site-directed', mutagenesis, and, 'DNA-protein', binding, assays, to, define, the, active, motifs, of, this, 'epsilon-globin', silencer])]). relacion([sujeto(['DNase', 'I', 'foot-printing', of, the, silencer, region, with, 'K562', cell]), verbo([nuclear]), complemento([extracts, defined, a, 'sequence,', which, we, designate, as, the, 'epsilon-globin', silencer, motif, or, epsilon, 'GSM', '(', epsilon, -, 278, to, -, 258, base, pairs, '(', 'bp))', containing, a, region, '(', epsilon, -, 270, to, -, 258, ')', with, 90, '%', homology, to, the, yeast, mating, type, 'silencer,', 'ABF-1', '(', autonomous, replicating, sequence, binding, factor, 'one)', and, which, also, overlaps, at, '(', epsilon, -, 269, to, -, 262, ')', with, the, human, 'YY1', consensus, 'sequence,', an, element, which, mediates, transcription, repression, and, activation, of, 'viral,', 'mouse,', and, human, genes])]). relacion([sujeto(['In', gel, mobility, shift, 'assays,', two, specific, proteins, '(', 'A', and, 'B)', in]), verbo([nuclear]), complemento([extracts, from, erythroleukemia, 'K562', cells, bound, to, the, 'DNase', 'I-footprinted', region])]). relacion([sujeto(['Protein', 'B,']), verbo([associated]), complemento([with, 'epsilon-globin', silencer, activity, in, 'vitro,', required, an, intact, epsilon, 'GSM', sequence, for, binding])]). relacion([sujeto(['Mutation', of, 5, bases, within, the, epsilon, 'GSM', in, an, 'epsilon-globin', 'promoter-containing', fragment, extending, upstream, to, 1400, bp, in, transient, transfection, assays]), verbo([increased]), complemento([activity, by, 3.0, -, fold, compared, with, the, native, 'sequence,', suggesting, that, the, silencer, activity, was, mediated, by, the, epsilon, 'GSM', sequence])]). relacion([sujeto(['We']), verbo([found]), complemento([that, protein, 'A', could, be, displaced, by, a, competitor, containing, the, 'GATA-1', consensus, 'sequence,', suggesting, that, protein, 'A', is, a, 'GATA-like', protein])]). relacion([sujeto(['The', region, from, -, 267, to, -, 271, within, the, epsilon, 'GSM', and, 'GATA-1', homology, region, was, important, for]), verbo([binding]), complemento([of, both, proteins, 'A', and, 'B'])]). relacion([sujeto(['These', data]), verbo([suggest]), complemento([that, protein, binding, to, the, epsilon, 'GSM', and, 'GATA', motifs, mediate, the, negative, effect, of, the, silencer, on, 'transcription,', possibly, via, direct, competition, for, binding, to, this, 'DNA', region])]). relacion([sujeto(['Recombinant', yeast, 'ABF-1', and, human, 'YY1']), verbo([bound]), complemento([to, the, epsilon, 'GSM'])]). relacion([sujeto(['Mutating', three, bases, '(', epsilon, -, 259, ',', -, 262, ',', -, 264, ')', in, the, epsilon, 'GSM']), verbo([decreased]), complemento([the, binding, affinity, of, protein, 'B', and, recombinant, human, 'YY1', but, increased, the, binding, affinity, of, recombinant, yeast, 'ABF-1'])]). relacion([sujeto(['We']), verbo([have]), complemento([established, the, essential, nature, of, 'GATA-1', during, both, primitive, and, definitive, erythropoiesis])]). relacion([sujeto(['We', can, now, study, regulatory, regions, and, functional, domains, of, the, protein, in, the, context, of, a, true, erythroid, 'environment,', experiments, that]), verbo([have]), complemento([not, been, possible, heretofore])]). relacion([sujeto(['Although', the, assay]), verbo([involves]), complemento([the, dramatic, loss, of, red, cell, 'production,', it, should, be, possible, to, define, important, regulatory, domains, that, can, then, be, assayed, using, less, stringent, 'systems,', such, as, 'cell-free', extracts, for, in, vitro, transcription])]). relacion([sujeto(['However,', these, cells]), verbo([have]), complemento([been, impossible, to, generate, given, the, requirement, of, 'GATA-1', for, 'Epo', receptor, expression, and, red, cell, viability, '(', 'C'])]). relacion([sujeto(['It', may, be, possible, to, produce, such, cells, by, first]), verbo([expressing]), complemento([the, 'Epo', receptor, under, the, influence, of, a, constitutive, promoter, and, then, targeting, the, 'GATA-1', gene])]). relacion([sujeto(['If', 'GATA-1-', red, cells, were, 'available,', the, analyses, would]), verbo([involve]), complemento([the, actual, transcription, of, or, chromatin, structure, surrounding, the, globin, genes])]). relacion([sujeto(['However,', the, 'ES', cell, system, can, be, used, as, an, alternative, until]), verbo([targeted]), complemento([erythroleukemia, cells, become, available])]). relacion([sujeto(['Other', applications]), verbo([involve]), complemento([the, introduction, of, other, 'GATA-binding', protein, family, members, to, determine, whether, they, rescue, the, mutation])]). relacion([sujeto(['How', does, 'GATA-1']), verbo([regulate]), complemento([red, cell, genes, like, globin, or, the, 'Epo', 'receptor?', 'Once', we, identify, the, functional, domains, of, the, 'GATA-binding', 'proteins,', we, hope, to, learn, what, proteins, 'GATA-1', binds, to, in, the, basic, transcription, machinery, or, in, chromatin])]). relacion([sujeto(['Is', 'GATA-1', necessary, for, globin, gene, 'switching?', 'GATA-1', may, be, modified, differently, during, development, so, that, the, locus, control, region, can]), verbo([interact]), complemento([with, different, globin, promoters])]). relacion([sujeto(['We', may]), verbo([find]), complemento([that, one, region, of, the, protein, is, required, for, embryonic, expression, and, another, for, adult, globin, gene, expression])]). relacion([sujeto(['Mutations', that, abolished, 'GATA-1']), verbo([binding]), complemento([at, a, single, position, in, the, promoter, prevented, interaction, with, 'enhancers,', whereas, elimination, of, a, second, more, distal, promoter, 'GATA-1', site, had, no, effect])]). relacion([sujeto(['Deletion', or, mutation, of, the, 'GATA-1', sites, in, either, the, human, 'beta-globin', locus, control, region, 'DNase-hypersensitive', site, 'II', enhancer, or, the, chicken, beta, 'A/epsilon-globin', enhancer, did, not, diminish, the, ability, of, the, enhancers, to]), verbo([interact]), complemento([with, the, promoter])]). relacion([sujeto(['In', vitro, transcription, of, these, constructs, was, promoter, dependent, and, was, not, sensitive, to, abolition, of, 'GATA-1']), verbo([binding]), complemento([in, the, 'promoter,', consistent, with, the, role, of, 'GATA-1', solely, as, a, mediator, of, the, enhancer, effect])]). relacion([sujeto(['Thus,', 'GATA-1']), verbo([regulates]), complemento([the, response, of, the, 'epsilon-globin', gene, to, enhancers, through, a, specific, site, in, the, promoter, and, requires, enhancer, 'AP-1/NF-E2', binding, to, transduce, the, enhancer, effect, on, transcription])]). relacion([sujeto(['Tal-1', rearrangements, are]), verbo([associated]), complemento([with, nearly, 30, '%', of, human, 'T', acute, lymphoblastic, leukemia])]). relacion([sujeto(['Tal-1', gene, encodes, a, putative, transcription, factor, with, a, basic, 'helix-loop-helix', domain, and, is, known, to, be, predominantly]), verbo([expressed]), complemento([in, hematopoietic, cells])]). relacion([sujeto(['Both', methods, demonstrated, that, the, 'tal-1', gene, is]), verbo([expressed]), complemento([in, megakaryocytes, and, erythroblasts, as, well, as, in, basophilic, granulocytes])]). relacion([sujeto(['We']), verbo([found]), complemento([that, 'GATA-1', and, 'tal-1', genes, are, coexpressed, in, these, three, lineages])]). relacion([sujeto(['In', 'contrast,', 'GATA-2', is, strongly]), verbo([expressed]), complemento([in, both, most, primitive, and, committed, progenitors, 'cells,', whereas, 'GATA-3', is, mostly, detected, in, most, primitive, ones])]). relacion([sujeto(['Altogether', our, results, strongly]), verbo([suggest]), complemento([that, 'GATA-1', modulates, the, transcription, of, 'tal-1', during, the, differentiation, of, the, 'erythroid,', 'megakaryocytic,', and, basosophilic, lineages])]). relacion([sujeto(['The', locus, for, the, erthyroid, transcription, 'factor,', 'GATA1,']), verbo([has]), complemento([been, positioned, in, the, small, interval, between, 'DXS255', and, 'TIMP', on, the, proximal, short, arm, of, the, human, 'X', 'Chromosome', '(', 'Chr)', by, use, of, a, partial, human, cDNA, clone, and, a, 'well-characterized', somatic, cell, hybrid, panel])]). relacion([sujeto(['These', data, imply, that, a, partial, inversion, of, gene, order]), verbo([has]), complemento([occurred, within, the, conserved, segment, that, represents, 'Xp21'])]). relacion([sujeto(['Furthermore,', they, indicate, that, the, mouse, mutant, scurfy, and, the, human, genetic, disorder, 'Wiskott-Aldrich', 'syndrome,', which]), verbo([have]), complemento([been, mapped, to, the, same, regions, as, 'GATA1/Gf-1', in, both, 'species,', may, indeed, be, homologous, disorders])]). relacion([sujeto(['We']), verbo([have]), complemento([investigated, interactions, between, the, erythroid, transcription, factor, 'GATA-1', and, factors, binding, two, 'cis-acting', elements, commonly, linked, to, 'GATA', sites, in, erythroid, control, elements])]). relacion([sujeto(['GATA-1', is, present, at, all, stages, of, erythroid, 'differentiation,', is, necessary, for, 'erythropoiesis,', and]), verbo([binds]), complemento([sites, in, all, erythroid, control, elements])]). relacion([sujeto(['A', mutation, of, 'T', to, 'C', at, position, -, 175, in, the, 'gamma-globin', promoter, 'GATA', 'site,']), verbo([associated]), complemento([with, hereditary, persistence, of, fetal, hemoglobin, '(', 'HPFH),', increased, expression, of, these, promoters, in, both, fetal, and, adult, cells])]). relacion([sujeto(['These', studies]), verbo([suggest]), complemento([that, erythroid, control, elements, are, formed, by, the, interactions, of, at, least, three, transcription, 'factors,', none, of, which, functions, alone])]). relacion([sujeto(['We']), verbo([have]), complemento([performed, a, detailed, analysis, of, the, 'cis-acting', sequences, involved, in, the, 'erythroid-specific', expression, of, the, human, glycophorin, 'B', '(', 'GPB)', promoter, and, found, that, this, promoter, could, be, divided, into, two, regions])]). relacion([sujeto(['The', proximal, 'region,', -, 1, to, -, 60, ',', contains, a, 'GATA']), verbo([binding]), complemento([sequence, around, -, 37, and, an, 'SP1', binding, sequence, around, -, 50])]). relacion([sujeto(['The', distal, 'region,', -, 60, to, -, 95, ',', contains, two, overlapping, protein]), verbo([binding]), complemento([sites, around, -, 75, ',', one, for, 'hGATA-1', and, one, for, ubiquitous, proteins])]). relacion([sujeto(['Using', site, directed, 'mutagenesis,', we, show, that, the, -, 37, 'GATA', and, the, -, 50, 'SP1']), verbo([binding]), complemento([sites, are, necessary, for, efficient, activity, of, the, -, 95, 'GPB', construct])]). relacion([sujeto(['Mutations', that, impair, the, -, 75, 'GATA-1']), verbo([binding]), complemento([result, in, extinction, of, the, -, 95, 'GPB', construct, activity, if, the, -, 75, ubiquitous, binding, site, is, not, 'altered,', or, in, loss, of, erythroid, specificity, if, the, -, 75, ubiquitous, binding, site, is, also, mutated])]). relacion([sujeto(['Using', a, cotransfection, 'assay,', we]), verbo([found]), complemento([that, 'hGATA-1', can, efficiently, activate, transcription, of, the, -, 95, 'GPB', construct, in, 'non-erythroid', cells])]). relacion([sujeto(['Mutations', that, impair, the, -, 75, 'GATA-1']), verbo([binding]), complemento([and, still, allow, the, -, 75, ubiquitous, binding, also, abolish, the, transactivation, of, the, -, 95, 'GPB', 'construct,', indicating, that, 'hGATA-1', can, remove, repression, of, the, 'GPB', promoter, by, displacement, of, the, ubiquitous, proteins])]). relacion([sujeto(['We']), verbo([found]), complemento([that, '(', 'i)', the, 'SCL', promoter, for, exon, 'Ia', contains, a, potential, recognition, site, for, 'GATA-binding', transcription, 'factors,', '(', 'ii)', 'SCL', mRNA, is, expressed, in, all, erythroid, tissues, and, cell, lines, 'examined,', and, '(', 'iii)', 'SCL', mRNA, increases, upon, induced, differentiation, of, murine, erythroleukemia, '(', 'MEL)', 'cells,', and, inferred, that, 'SCL', may, play, a, physiologic, role, in, erythroid, differentiation])]). relacion([sujeto(['We', used, gel, shift, and, transfection, assays, to, demonstrate, that, the, 'GATA', motif, in, the, 'SCL', promoter]), verbo([binds]), complemento(['GATA-1', '(', and, 'GATA-2),', and, also, mediates, transcriptional, transactivation])]). relacion([sujeto(['Increasing', the, level, of, 'SCL', expression, in, two, independent, 'MEL', lines, '(', 'F4-6', and, 'C19,', a, 745, 'derivative)', and, 'K562', cells]), verbo([increased]), complemento([the, rate, of, spontaneous, '(', i])]). relacion([sujeto(['Conversely,']), verbo([induced]), complemento([differentiation, was, inhibited, in, 'MEL', transfectants, expressing, either, antisense, 'SCL', cDNA, or, a, mutant, 'SCL', lacking, the, basic, domain])]). relacion([sujeto(['Our', experiments]), verbo([suggest]), complemento([that, the, 'SCL', gene, can, be, a, target, for, the, erythroid, transcription, factor, 'GATA-1', and, that, the, 'SCL', gene, product, serves, as, a, positive, regulator, of, erythroid, differentiation])]). relacion([sujeto(['Since', the, mutation, '(', 'TTATCT-TCATCT)', is, located, within, the, inverted]), verbo([binding]), complemento([motif, of, 'GATA-1', '(', 'T', or, 'A-G-A-T-A-G', or, 'A),', an, erythroid, 'cell-specific', transcription, 'factor,', we, did, gel, retardation, assays, using, nuclear, extracts, from, the, erythroid, cells])]). relacion([sujeto(['We']), verbo([found]), complemento([that, 'GATA-1', binds, the, oligonucleotide, spanning, positions, -, 61, to, -, 90, ',', but, does, not, bind, to, the, oligonucleotide, with, the, mutation, at, position, -, 77])]). relacion([sujeto(['Competition', gel, retardation, assays, showed, that, 'GATA-1']), verbo([binding]), complemento([can, be, competed, out, by, the, fragment, with, the, 'GATA-1', 'motif,', but, not, with, the, mutant, oligonucleotide])]). relacion([sujeto(['Analysis', of, the, transient, expression, of, the, 'CAT', gene, linked, to, the, 'delta-globin', gene, promoter, region, demonstrated, that, the, construct, with, the, mutant, promoter, region, was]), verbo([expressed]), complemento([about, 20, -, fold, less, compared, with, the, normal, one])]). relacion([sujeto(['Thus,', the, mutation, at, position, -, 77, impairs, 'delta-globin', gene, expression, by, abolishing, 'GATA-1']), verbo([binding]), complemento([to, the, 'AGATAA', sequence, of, the, promoter, region, of, the, 'delta-globin', gene])]). relacion([sujeto(['This']), verbo([provides]), complemento([a, good, example, of, involvement, of, 'tissue-specific', transacting, factors, in, the, molecular, pathogenesis, of, hereditary, diseases])]). relacion([sujeto(['The', 'CACCC', region, and, the, region, containing, the]), verbo([binding]), complemento([sites, for, protein, 'GATA-1', behaved, as, activator, domains])]). relacion([sujeto(['The', programmed, 'activation/repression', of, transcription, factors, in, early, hematopoietic, differentiation]), verbo([has]), complemento([not, yet, been, explored])]). relacion([sujeto(['The', 'DNA-binding', protein, 'GATA-1', is]), verbo([required]), complemento([for, normal, erythroid, development, and, regulates, 'erythroid-expressed', genes, in, maturing, erythroblasts])]). relacion([sujeto(['We', analyzed, 'GATA-1', expression, in, early, human, adult, hematopoiesis, by, using, an, in, vitro, system, in, which, &, 'quot;pure"', early, hematopoietic, progenitors, are]), verbo([induced]), complemento([to, gradual, and, synchronized, differentiation, selectively, along, the, erythroid, or, 'granulocyte-macrophage', pathway, by, differential, treatment, with, hematopoietic, growth, factors])]). relacion([sujeto(['The', 'GATA-1', 'gene,', though, virtually, silent, in, quiescent, 'progenitors,', is]), verbo([activated]), complemento([after, entrance, into, the, cell, cycle, upon, stimulation, with, hematopoietic, growth, factors])]). relacion([sujeto(['Subsequently,']), verbo([increasing]), complemento([expression, along, the, erythroid, pathway, contrasts, with, an, abrupt, downregulation, in, the, 'granulocyte-macrophage', lineage])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([a, 'microenvironment-directed,', 'two-step', model, for, 'GATA-1', expression, in, differentiating, hematopoietic, progenitors, that, involves, '(', 'i)', 'cycle-dependent', initiation, and, '(', 'ii)', 'lineage-dependent', maintenance, or, suppression])]). relacion([sujeto(['Thus,', studies, on, the, regulation, of, this, gene, may]), verbo([provide]), complemento([helpful, information, on, the, mechanisms, controlling, cell, specificity, and, differentiation, in, this, lineage])]). relacion([sujeto(['A', region, extending, from, nucleotides, -, 414, to, -, 554, was]), verbo([found]), complemento([to, be, extremely, important, for, the, promoter, function])]). relacion([sujeto(['Deletion', of, this, region, results, in, a, 70, '%']), verbo([decrease]), complemento([of, the, promoter, 'activity,', as, measured, in, 'CAT', assays])]). relacion([sujeto(['This', region]), verbo([has]), complemento([the, properties, of, an, enhancer])]). relacion([sujeto(['It', is, able, to]), verbo([activate]), complemento([a, heterologous, 'promoter,', in, a, 'distance-', and, 'orientation-independent', 'manner,', in, both, megakaryocytic, and, erythroid, cells])]). relacion([sujeto(['This', enhancer, contains]), verbo([binding]), complemento([sites, for, nuclear, factors, and, mutation, of, these, 'sites,', individually, or, 'together,', abolish, the, enhancer, activity])]). relacion([sujeto(['These']), verbo([nuclear]), complemento([factors, are, present, in, megakaryocytic, and, erythroid, cell, 'lineages,', but, they, are, absent, in, the, other, tested, cells])]). relacion([sujeto(['One', of, the, 'sites,', named, domain, 'D,', contains, a, 'TTATC', motif, that, may]), verbo([interact]), complemento([with, the, transcription, factor, 'GATA1,', active, in, erythroid, and, megakaryocytic, cells])]). relacion([sujeto(['We']), verbo([have]), complemento([recently, shown, that, 'ME26', virus, can, induce, erythropoietin, '(', 'Epo)', responsiveness, in, hematopoietic, cells])]). relacion([sujeto(['In', 'vitro,', 'ME26', virus, specifically]), verbo([induces]), complemento(['Epo', responsiveness, in, the, 'interleukin-3-dependent', myeloid, cell, line, 'FDC-P2', by, enhancing, expression, of, the, 'Epo', receptor, '(', 'EpoR)'])]). relacion([sujeto(['In', the, present, study, we, demonstrate, that, 'ME26', virus, infection, of, 'FDC-P2', cells, also, results, in]), verbo([enhanced]), complemento([expression, of, 'beta-globin', and, the, 'erythroid-specific', transcription, factor, 'GATA-1,', a, protein, which, can, transactivate, both, the, 'EpoR', promoter, and, globin, genes])]). relacion([sujeto(['Our', results, indicate, that, while, 'ME26', virus, did, not, directly]), verbo([enhance]), complemento([expression, from, the, 'EpoR', 'promoter,', both, it, and, its, avian, 'parent,', 'E26,', transactivated, the, 'GATA-1', promoter])]). relacion([sujeto(['Furthermore,', 'ME26', virus, cooperates, with, the, 'GATA-1', protein, to]), verbo([enhance]), complemento([expression, of, the, 'EpoR', gene])]). relacion([sujeto(['We', propose, that, the, mechanism, by, which, 'ME26', virus]), verbo([induces]), complemento([erythroleukemia, involves, transactivation, of, the, 'GATA-1', 'gene,', thus, positively, regulating, the, expression, of, the, 'EpoR', and, leading, to, the, proliferation, of, a, unique, population, of, 'Epo-responsive', cells])]). relacion([sujeto(['By', specifically]), verbo([inducing]), complemento(['Epo', responsiveness, in, hematopoietic, cells, via, transactivation, of, a, transcription, 'factor,', 'ME26', virus, utilizes, a, novel, mechanism, for, retrovirus, pathogenesis])]). relacion([sujeto(['Development', of, definitive, '(', fetal, 'liver-derived)', red, cells, is, blocked, by, a]), verbo([targeted]), complemento([mutation, in, the, gene, encoding, the, transcription, factor, 'GATA-1'])]). relacion([sujeto(['We', used, in, vitro, differentiation, of, 'GATA-1-', mouse, embryonic, stem, '(', 'ES)', cells, to]), verbo([reveal]), complemento([a, requirement, for, 'GATA-1', during, primitive, '(', yolk, 'sac-derived)', erythropoiesis, and, to, establish, a, rescue, assay])]). relacion([sujeto(['Use', of, in, vitro, differentiated, 'ES', cells, bridges, a, gap, between, conventional, approaches, to, gene, function, in, cell, lines, and, analysis, of]), verbo([loss]), complemento([of, function, mutations, in, the, whole, animal])]). relacion([sujeto(['The', 'SCL', gene, encodes, a, putative, transcription, factor, with, a, basic, 'helix-loop-helix', '(', 'B-HLH)', motif, and, is, known, to, be, predominantly]), verbo([expressed]), complemento([in, erythroid, cells])]). relacion([sujeto(['SCL', is, therefore]), verbo([expressed]), complemento([in, the, same, three, lineages, as, 'GATA-1,', a, 'well-recognized', hemopoietic, transcription, factor])]). relacion([sujeto(['Thus', 'SCL', and, 'GATA-1', are, coordinately]), verbo([expressed]), complemento([in, multiple, hemopoietic, lineages, and, coordinately, regulated, during, induced, erythroid, and, myeloid, differentiation])]). relacion([sujeto(['This']), verbo([suggests]), complemento([a, previously, unexpected, role, for, 'SCL', in, neural, differentiation])]). relacion([sujeto(['The', principal, regulator, of, erythropoiesis, is, the, glycoprotein, 'erythropoietin,', which]), verbo([interacts]), complemento([with, a, specific, cell, surface, receptor, '(', 'EpoR)'])]). relacion([sujeto(['A', study, aimed, at, analyzing, 'EpoR', gene, regulation]), verbo([has]), complemento([shown, that, both, pluripotent, embryonal, stem, cells, and, early, multipotent, hematopoietic, cells, express, 'EpoR', transcripts])]). relacion([sujeto([',', macrophage, or, 'lymphocytic)', results, in, the, shutdown, of, 'EpoR', gene, 'expression,', whereas, commitment, to, the, erythroid, lineage, is, concurrent, with, or, followed, by, dramatic]), verbo([increases]), complemento([in, 'EpoR', transcription])]). relacion([sujeto(['In', 'addition,', a, third, major, 'HSS', also, located, within, the, first, intron, of, the, 'EpoR', gene, is, uniquely, present, in, erythroid, cells, that]), verbo([express]), complemento([high, levels, of, 'EpoR'])]). relacion([sujeto(['Transfection', assays, show, that, sequences, surrounding, this, major, 'HSS', impart, erythroid, 'cell-specific', enhancer, activity, to, a, heterologous, promoter, and, that, this, activity, is, at, least, in, part]), verbo([mediated]), complemento([by, 'GATA-1'])]). relacion([sujeto(['We']), verbo([have]), complemento([previously, described, a, family, of, 'Northern', 'Sardinian', descent, in, which, the, propositus, was, affected, by, thalassemia, major, resulting, from, compound, heterozygosity, for, codon, 39, nonsense, mutation, and, the, beta, +, 'IVS', 'II', nt, 745, mutation, and, in, which, all, heterozygotes, for, the, beta, +, 'IVS', 'II', nt, 745, mutation, had, normal, hemoglobin, '(', 'Hb)', 'A2', levels])]). relacion([sujeto(['The', normal, 'G', at, position, 69, is, part, of, a, sequence, very, similar, to, the, core, 'DNA', '(', 'A/T)GATA(A/G)', motif, '(', 'GATA', 'box)', that, is, a]), verbo([binding]), complemento([site, for, the, 'GATA-1', protein])]). relacion([sujeto(['Gel-retardation', assay]), verbo([has]), complemento([shown, that, a, 'DNA', fragment, containing, the, 'GATA', motif, with, the, 'G----A', at, position, +, 69, has, increased, binding, affinity, for, 'erythroid-specific', 'DNA', binding, 'protein(s)', as, compared, with, the, 'wild-type', sequence])]). relacion([sujeto(['These', findings, may]), verbo([suggest]), complemento([that, the, delta, +, 69, mutation, is, responsible, for, the, deficient, function, of, the, in, cis, 'delta-globin', gene])]). relacion([sujeto(['Some', of, the, elements]), verbo([involved]), complemento([in, the, 'erythroid-specific', transcriptional, regulation, of, the, human, 'gamma-', and, 'beta-globin', genes, and, located, inside, or, in, the, immediate, proximity, of, these, genes, have, been, identified, as, sequences, which, bind, 'erythroid-specific', factors])]). relacion([sujeto(['In', the, present, 'study,', we]), verbo([found]), complemento([two, regions, located, within, 1, kb, in, 5, '\'', to, the, alpha, 2, -, and, in, 3, '\'', to, the, alpha, 1, -, globin, genes, which, contribute, to, the, induction, of, human, 'alpha-globin', genes, following, erythroid, differentiation, in, stable, 'MEL', transformants])]). relacion([sujeto(['GATA-1', is]), verbo([expressed]), complemento([widely, among, the, 'nonerythroid,', 'factor-dependent', subclones, of, the, interleukin, 3, -, dependent, mouse, cell, line, 32, 'D'])]). relacion([sujeto(['Consequently,', to, determine, whether, 'GATA-1', and, 'EpoR', gene, expression, are, linked, even, in, nonerythroid, 'cells,', we]), verbo([have]), complemento([studied, the, correlation, of, 'GATA-1', expression, with, expression, and, function, of, 'EpoR', in, these, cell, lines])]). relacion([sujeto(['However,', only, 32, 'D', 'Epo', cells]), verbo([bound]), complemento([125, 'I-labeled', 'Epo', and, expressed, 'EpoR', protein, on, the, cell, 'surface,', as, determined, by, immunoprecipitation, of, 'surface-labeled', proteins])]). relacion([sujeto(['Erythropoietin']), verbo([interacts]), complemento([with, 'high-affinity', cell, surface, receptors, '(', 'EpoR)', present, on, developing, progenitors, and, is, required, for, their, survival])]). relacion([sujeto(['Previously', we, characterized, the, gene, for, 'EpoR', and, demonstrated, that, its, promoter]), verbo([acts]), complemento([in, a, 'cell-specific', manner])]). relacion([sujeto(['Hence,', 'GATA-1,', which]), verbo([participates]), complemento([in, transcriptional, control, of, the, majority, of, 'erythroid-expressed', 'genes,', also, acts, on, the, promoter, of, an, essential, 'lineage-restricted', receptor, '(', 'EpoR)'])]). relacion([sujeto(['This', central, contribution, of, 'GATA-1', to, 'EpoR', promoter, function]), verbo([provides]), complemento([a, mechanism, whereby, a, 'cell-restricted', regulator, may, ensure, the, viability, and, subsequent, maturation, of, progenitor, cells, during, hematopoietic, differentiation])]). relacion([sujeto(['The', transcription, factor, 'GATA-1', is]), verbo([expressed]), complemento([in, a, subset, of, hemopoietic, 'cells,', where, it, mediates, the, 'cell-type', specific, expression, of, several, genes])]). relacion([sujeto(['We']), verbo([have]), complemento([cloned, the, mouse, and, human, 'GATA-1', genes])]). relacion([sujeto(['A', region, upstream, to, the, first, 'exon,', and, highly]), verbo([conserved]), complemento([between, mouse, and, 'man,', acts, as, an, erythroid, specific, enhancer, in, transient, 'assays,', if, linked, to, the, 'GATA-1', or, to, the, 'SV40', promoter])]). relacion([sujeto(['The', activity, of, the, enhancer, is, almost, completely, dependent, on, the, integrity, of, a, dimeric, 'GATA-1']), verbo([binding]), complemento([site])]). relacion([sujeto(['Presence', in, cis, of, 5, '\'', 'HS-2']), verbo([confers]), complemento([a, high, level, of, erythroid, 'cell-specific', and, developmentally, regulated, promoter, activities, of, human, globin, genes, in, transfected, cell, cultures, and, in, transgenic, mice])]). relacion([sujeto(['Combining', the, use, of, the, methylation, protection, assay, and, polymerase, chain, 'reaction,', we]), verbo([have]), complemento([studied, nuclear, 'factor-DNA', interactions, of, the, 5, '\'', 'HS-2', enhancer, in, vitro, and, in, vivo])]). relacion([sujeto(['First,', a, 'GATA-1', motif, was]), verbo([found]), complemento([to, bind, nuclear, 'factor(s),', presumably, the, 'GATA-1', 'factor,', present, in, 'K-562', cell, extracts, and, in, living, 'K-562', cells])]). relacion([sujeto(['No', such]), verbo([binding]), complemento([was, seen, in, nonerythroid, 'HeLa', cells, or, extract])]). relacion([sujeto(['A', second, 'motif,', 'NF-E2/AP1', '(']), verbo([nuclear]), complemento(['factor-erythroid', 2, /, activator, protein, 1, ')', ',', consists, of, tandemly, arranged, dimers, of, 'AP1', binding, consensus])]). relacion([sujeto(['In', vivo, methylation, protection, patterns, of, this, motif, parallel, those, observed, in, 'vitro,']), verbo([suggesting]), complemento([that, it, is, also, bound, by, 'NF-E2', in, 'K-562', cells, and, by, 'AP1', in, 'HeLa', cells])]). relacion([sujeto(['Finally,', a, 'GT-I', motif]), verbo([binds]), complemento([apparently, to, one, or, more, similar, factors, in, both, types, of, nuclear, 'extracts,', but, the, in, vivo, methylation, protection, patterns, are, not, identical, between, living, 'HeLa', and, 'K-562', cells])]). relacion([sujeto(['These', data]), verbo([provide]), complemento([direct, evidence, that, specific, nuclear, 'factor-DNA', complexes, form, in, vivo, at, functionally, important, sequence, motifs, of, the, 5, '\'', 'HS-2', enhancer, in, erythroid, cells])]). relacion([sujeto(['The', detection, of, conformationally, different]), verbo([nuclear]), complemento(['factor-DNA', complexes, at, the, same, sequence, motifs, in, 'HeLa', and, 'Raji', cell, lines, also, raises, interesting, questions, regarding, the, origin, and, function, of, these, complexes, in, nonerythroid, cells])]). relacion([sujeto(['Erythropoietin', is, a, cytokine, which, specifically]), verbo([regulates]), complemento([the, proliferation, and, differentiation, of, erythroid, progenitor, cells])]). relacion([sujeto(['Furthermore,', 'Northern', blot, analysis, revealed, that, erythropoietin, 'receptor-mediated', signals, strongly]), verbo([enhanced]), complemento(['GATA-1', gene, expression, in, accordance, with, the, appearance, of, 'hemoglobin-positive', cells])]). relacion([sujeto(['Taken', together, with, other, 'observations,', these, results]), verbo([suggested]), complemento([the, following, scheme, of, erythroid, 'differentiation:', 1, ')', 'GATA-1', is, expressed, in, the, early, stage, of, blood, cell, 'development;', 2, ')', 'GATA-1', transactivates, the, erythropoietin, receptor, 'gene;', 3, ')', erythropoietin, binds, its, receptor, and, the, 'receptor-mediated', signals, enhance, 'GATA-1', gene, expression, in, erythroid, progenitor, 'cells;', and, 4, ')', 'GATA-1', finally, transactivates, hemoglobin, 'synthesis-related', genes, and, globin, genes, in, relatively, matured, erythroid, cells])]). relacion([sujeto(['It', can, be, deduced, that, the, erythroid, 'ALAS', precursor, protein]), verbo([has]), complemento([a, molecular, weight, of, 64.6, 'kd,', and, is, similar, in, size, to, the, previously, isolated, human, housekeeping, 'ALAS', precursor, of, molecular, weight, 70.6, kd])]). relacion([sujeto(['The', mature, mitochondrial, forms, of, the, erythroid, and, housekeeping, 'ALAS', isozymes, are, predicted, to]), verbo([have]), complemento([molecular, weights, of, 59.5, kd, and, 64.6, 'kd,', respectively])]). relacion([sujeto(['The', two, isozymes, show, little, amino, acid, identity, in, their, 'N-terminal', signal, sequences, but]), verbo([have]), complemento([considerable, sequence, identity, in, the, 'C-terminal', 'two-thirds', of, their, proteins])]). relacion([sujeto(['An', analysis, of, the, immediate, promoter, of, the, human, erythroid, 'ALAS', gene, revealed, several, putative, 'erythroid-specific', 'cis-acting', elements, including, both, a, 'GATA-1', and, an, 'NF-E2']), verbo([binding]), complemento([site])]). relacion([sujeto(['An', 'iron-responsive', element, '(', 'IRE)', motif]), verbo([has]), complemento([been, identified, in, the, 5, '\'', -, untranslated, region, of, the, human, erythroid, 'ALAS', 'mRNA,', but, is, not, present, in, the, housekeeping, 'ALAS', mRNA])]). relacion([sujeto(['Gel', retardation, experiments, established, that, this, 'IRE', motif, formed, a, protein, -, 'RNA', complex, with, cytosolic, extracts, from, human, 'K562', cells, and, this]), verbo([binding]), complemento([was, strongly, competed, with, 'IRE', transcripts, from, ferritin, or, transferrin, receptor, mRNAs])]). relacion([sujeto(['A', transcript, of, the, 'ALAS', 'IRE,', mutated, in, the]), verbo([conserved]), complemento([loop, of, the, 'IRE,', did, not, readily, form, this, protein, -, 'RNA', complex])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, the, 'IRE', motif, in, the, 'ALAS', mRNA, is, functional, and, imply, that, translation, of, the, mRNA, is, controlled, by, cellular, iron, availability, during, erythropoiesis])]). relacion([sujeto(['We']), verbo([report]), complemento([here, the, cloning, of, a, human, cDNA, for, a, new, member, of, this, family])]). relacion([sujeto(['This', 'member,', called, 'hGATA3,']), verbo([has]), complemento([85, '%', amino, acid, homology, with, hGATA1, in, the, 'DNA-binding', domain, and, no, homology, elsewhere, in, the, protein])]). relacion([sujeto(['The', encoded, hGATA3, 'protein,', made, in, an, in, vitro, 'transcription-translation', 'assay,']), verbo([binds]), complemento([the, 'WGATAR', motif, present, in, the, human, 'T-cell', receptor, '(', 'TCR)', delta, gene, enhancer, 'and,', by, transfection, in, 'HeLa', 'cells,', we, show, that, hGATA3, can, transactivate, this, 'TCR', delta, gene, enhancer])]). relacion([sujeto(['Interestingly', this, enhancer]), verbo([binds]), complemento([and, is, also, transactivated, by, hGATA1])]). relacion([sujeto(['Conversely,', the, promoter, of, the, human, glycophorin, 'B', '(', 'GPB),', which, is, 'erythroid-specific', and, contains, two, 'WGATAR', 'motifs,']), verbo([binds]), complemento([and, is, transactivated, by, hGATA1, 'and,', to, a, lesser, 'extent,', by, hGATA3])]). relacion([sujeto(['These', results, indicate, that, the, activation, of, specific, genes, by, hGATA1, or, hGATA3, is, partly, governed, by, the, lineage, expression, of, these, two, factors, during, haematopoiesis, and, 'that,', in, the, 'T-cell', 'lineage,', hGATA3]), verbo([binds]), complemento([the, human, 'TCR', delta, gene, enhancer, and, is, involved, in, its, expression])]). relacion([sujeto(['Transcription', of, 'erythroid-expressed', genes, and, normal, erythroid, development, in, vivo, are, dependent, on, a, regulatory, protein, '(', 'GATA-1)', that]), verbo([recognizes]), complemento([a, consensus, 'GATA', motif])]). relacion([sujeto(['During', cellular, maturation, the, levels, of, 'GATA-1', 'RNA', and, protein]), verbo([increase]), complemento([progressively])]). relacion([sujeto(['In', an, effort, to, delineate, mechanisms, by, which, this, pivotal, transcription, factor, is, itself]), verbo([regulated]), complemento([we, have, characterized, the, mouse, 'GATA-1', gene, and, 'cis-elements', within, its, promoter])]). relacion([sujeto(['We']), verbo([find]), complemento([that, the, isolated, promoter, retains, cell, specificity, exhibited, by, the, intact, gene])]). relacion([sujeto(['Full', promoter, activity]), verbo([requires]), complemento([the, presence, of, proximal, 'CACCC', box, sequences, and, an, 'upstream,', double, 'GATA', motif, that, binds, a, single, 'GATA-1', molecule, in, an, asymmetric, fashion])]). relacion([sujeto(['Using', in, vivo, footprinting, of, mouse, erythroleukemic, cells, we, detect, protein]), verbo([binding]), complemento([in, vivo, to, both, 'cis-elements'])]). relacion([sujeto(['On', the, basis, of, these, findings, we, propose, that, a, positive, feedback, loop]), verbo([mediated]), complemento([through, 'GATA-1', serves, two, complementary, 'functions:', maintenance, of, the, differentiated, state, by, locking, the, promoter, into, an, &, 'quot;on"', 'state,', and, programming, the, progressive, increase, in, protein, content, throughout, cellular, maturation])]). relacion([sujeto(['The', 'epsilon-globin', gene, is, the, first, of, the, human, 'beta-like', globin, genes, to, be]), verbo([expressed]), complemento([during, development])]). relacion([sujeto(['We']), verbo([have]), complemento([analyzed, 'protein-DNA', interactions, in, the, 'epsilon-globin', promoter, region, by, 'DNase', 'I', footprinting, and, electrophoretic, mobility, shift, experiments, using, nuclear, extracts, from, 'K562', human, erythroid, cells, and, from, nonerythroid, 'HeLa', cells])]). relacion([sujeto(['A', restricted, set, of, ubiquitous, 'proteins,', including, 'Sp1,']), verbo([bound]), complemento([to, regions, of, the, promoter, including, the, 'CACCC', and, 'CCAAT', sites])]). relacion([sujeto(['Three', 'interactions,', at, positions, -, 213, ',', -, 165, ',', and, +, 3, relative, to, the, transcription, start, 'site,', were, erythroid, specific, and, corresponded, to]), verbo([binding]), complemento([of, 'GATA-1,', a, transcription, factor, highly, restricted, to, the, erythroid, lineage])]). relacion([sujeto(['Interestingly,', the, 'GATA-1', site, at, -, 165]), verbo([has]), complemento([been, conserved, in, the, promoters, of, 10, mammalian, embryonic, globin, genes])]). relacion([sujeto(['Point', mutations, demonstrate, that, 'GATA-1']), verbo([binding]), complemento([to, this, site, is, necessary, for, interaction, with, an, 'erythroid-specific', enhancer, but, that, in, the, absence, of, an, 'enhancer,', 'GATA-1', does, not, increase, transcription])]). relacion([sujeto(['The', 'TCR', alpha, enhancer, contains, four]), verbo([nuclear]), complemento([protein, binding, sites, called, 'T', alpha, 1, -, 'T', alpha, 4])]). relacion([sujeto(['In', this]), verbo([report]), complemento([we, describe, the, identification, and, characterization, of, a, novel, human, 'cDNA,', 'hGATA-3', that, binds, to, the, 'T', alpha, 3, element, of, the, human, 'TCR', alpha, enhancer])]). relacion([sujeto(['hGATA-3', contains, a, zinc, finger, domain, that, is, highly, related, to, the, 'DNA-binding', domain, of, the, 'erythroid-specific', transcription, 'factor,', 'GATA-1,', and]), verbo([binds]), complemento([to, a, region, of, 'T', alpha, 3, that, contains, a, consensus, 'GATA', binding, site, '(', 'AGATAG)'])]). relacion([sujeto(['Northern', blot, analyses, of, hematopoietic, cell, lines, demonstrate, that, 'hGATA-3', is]), verbo([expressed]), complemento([exclusively, in, 'T', cells])]). relacion([sujeto(['Overexpression', of, 'hGATA-3', in, 'HeLa', cells, or, human, 'B', cells, specifically]), verbo([activated]), complemento([transcription, from, a, 'co-transfected', reporter, plasmid, containing, two, copies, of, the, 'T', alpha, 3, binding, site, located, upstream, of, the, minimal, 'SV40', promoter])]). relacion([sujeto(['Taken', together, these, results, demonstrate, that, 'hGATA-3', is, a, novel, 'lineage-specific', hematopoietic, transcription, factor, that, appears, to, play, an, important, role, in]), verbo([regulating]), complemento([the, 'T', 'cell-specific', expression, of, the, 'TCR', alpha, gene])]). relacion([sujeto(['The', 'LCR']), verbo([confers]), complemento([copy, number, dependent, high, levels, of, erythroid, specific, expression, to, a, linked, 'transgene,', independent, of, the, site, of, integration])]). relacion([sujeto(['To', assess, the, role, of, the, individual, hypersensitive, sites, of, the, 'LCR,', we]), verbo([have]), complemento([localized, 'HSS4', to, a, 280, bp, fragment, that, is, functional, both, in, murine, erythroleukaemia, '(', 'MEL)', cells, and, in, transgenic, mice])]). relacion([sujeto(['Bandshift', analysis, shows, that, these, footprints, correspond, to]), verbo([binding]), complemento([sites, for, the, erythroid, specific, proteins, 'GATA1', and, 'NF-E2', and, a, number, of, ubiquitous, 'proteins,', including, 'jun/fos,', 'Sp1', and, 'TEF2'])]). relacion([sujeto(['The', 'zinc-finger', transcription, factor, 'GATA-1', '(', previously, known, as, 'GF-1,', 'NF-E1', or, 'Eryf', 1]), verbo([binds]), complemento([to, 'GATA', consensus, elements, in, regulatory, regions, of, the, 'alpha-', and, 'beta-globin', gene, clusters, and, other, erythroid, 'cell-specific', genes])]). relacion([sujeto(['Analysis', of, the, effects, of, mutations, in, 'GATA-binding', sites, in, cell, culture, and, in]), verbo([binding]), complemento([assays, in, 'vitro,', as, well, as, transactivation, studies, with, 'GATA-1', expression, vectors, in, heterologous, 'cells,', have, provided, indirect, evidence, that, this, factor, is, involved, in, the, activation, of, globin, and, other, genes, during, erythroid, cell, maturation])]). relacion([sujeto(['GATA-1', is, also]), verbo([expressed]), complemento([in, megakaryocytes, and, mast, 'cells,', but, not, in, other, blood, cell, lineages, or, in, 'non-haemopoietic', cells])]). relacion([sujeto(['This', demonstrates, that, 'GATA-1', is]), verbo([required]), complemento([for, the, normal, differentiation, of, erythroid, 'cells,', and, that, other, 'GATA-binding', proteins, cannot, compensate, for, its, absence])]). relacion([sujeto(['The', transcriptional]), verbo([binding]), complemento([protein, 'NFE-1', '(', also, called, 'GF-1', and, 'Ery-f1)', is, thought, to, play, a, 'necessary,', but, not, 'sufficient,', role, in, the, regulation, of, 'differentiation-related', gene, expression, in, a, subset, of, hematopoietic, lineages, '(', 'erythroid,', 'megakaryocytic,', and, 'basophil-mast', 'cell)'])]). relacion([sujeto(['In', order, to, clarify, the, mechanism, which, underlies, the, 'lineage-specificity', of, the, 'NFE-1', 'expression,', as, well, as, the, relationship, between, the, expression, of, this, factor, and, growth, factor, 'responsiveness,', we]), verbo([have]), complemento([evaluated, the, capacity, of, erythropoietin, '(', 'Epo)-,', granulomonocytic, '(', 'GM)-colony', stimulating, factor, '(', 'CSF)-,', and, granulocyte, '(', 'G)-CSF-dependent', subclones, derived, from, the, interleukin, 3, '(', 'IL-3)-dependent', cell, line, 32, 'D,', to, express, 1, ')', 'NFE-1', 'mRNA,', 2, ')', 'NFE-1-related', nuclear, 'proteins,', and, 3, ')', chloramphenicol, acetyl, transferase, '(', 'CAT)', activity, when, transfected, with, a, 'CAT', gene, under, the, control, of, 'NFE-1', cognate, sequences])]). relacion([sujeto(['NFE-1', mRNA, was]), verbo([found]), complemento([to, be, expressed, not, only, in, cells, with, mast, cell, '(', 'IL-3-dependent', 32, 'D)', and, erythroid, '(', 'Epo-dependent', 32, 'D', 'Epo1)', 'phenotypes,', but, also, in, cells, with, predominantly, 'granulocyte/macrophage', 'properties,', such, as, the, 'GM-CSF-', '(', early, 'myelomonocytic)', and, 'G-CSF-', '(', 'myelocytic)', dependent, subclones, of, 32, 'D'])]). relacion([sujeto(['However,', a, gradient, of, 'expression,', correlating, with, the, 'lineage,', the, stage, of, 'differentiation,', and, the, growth, factor, responsiveness, of, the, cell, 'lines,', was]), verbo([found]), complemento([among, the, different, 'subclones:', 'Epo', greater, than, or, equal, to, 'IL-3', greater, than, 'GM-CSF', greater, than, 'G-CSF'])]). relacion([sujeto(['Human', glycophorin, 'C', '(', 'GPC)', is, an, integral, membrane, protein]), verbo([found]), complemento([in, many, cell, types, but, which, exhibits, increased, expression, in, red, cells])]). relacion([sujeto(['We']), verbo([have]), complemento([investigated, the, in, vitro, binding, of, nuclear, protein, factors, to, the, 'GPC', gene, 5, '\'', -, flanking, region, which, was, transcriptionally, active, when, transfected, into, erythroid, and, 'non-erythroid', cells])]). relacion([sujeto(['We']), verbo([found]), complemento([that, in, addition, to, known, ubiquitous, or, erythroid, 'trans-acting', 'factors,', a, presently, uncharacterized, 'erythroid/megakaryocyte-specific', protein, binds, the, 'GPC', promoter])]). relacion([sujeto(['These', data]), verbo([suggest]), complemento([that, 'NFE-6,', like, the, well, characterized, 'NFE-1', 'factor,', is, 'tissue-', but, not, 'stage-specific', and, is, conserved, across, species])]). relacion([sujeto(['It', is, proposed, that, 'NFE-6', might, be]), verbo([involved]), complemento([in, the, quantitative, change, in, the, expression, of, the, 'house-keeping', 'GPC', gene, related, to, red, cell, specialization])]). relacion([sujeto(['We']), verbo([have]), complemento([used, 'DNAase', 'I', footprinting, and, the, gel, mobility, shift, assay, to, study, proteins, which, bind, to, promoter, elements, located, between, -, 140, and, -, 382, upstream, of, the, human, 'A', gamma, globin, gene])]). relacion([sujeto(['Footprints', are]), verbo([found]), complemento([with, both, erythroid, and, nonerythroid, nuclear, extracts, at, three, 'sites:', from, -, 294, to, -, 264, ',', -, 242, to, -, 227, ',', and, -, 189, to, -, 172, from, the, transcription, initiation, site])]). relacion([sujeto(['We', demonstrate, that, two, known, transcription, 'factors,', the, ubiquitous, 'octamer-binding', protein, 'OTF-1', and, the, erythroid, regulatory, factor, 'NFE-1,']), verbo([bind]), complemento([to, the, -, 194, to, -, 172, region, and, that, their, footprints, overlap])]). relacion([sujeto(['Binding', of, 'OTF-1', to, this, region, is, reduced, by, a, mutation, at, -, 175]), verbo([associated]), complemento([with, a, form, of, 'non-deletion', hereditary, persistence, of, fetal, hemoglobin])]). relacion([sujeto(['We', conclude, that, 'OTF-1', may, compete, with, 'NFE-1', for, the, -, 175]), verbo([binding]), complemento(['site,', possibly, functioning, as, a, repressor, of, gamma, globin, transcription])]). relacion([sujeto(['Human', parturition, is]), verbo([associated]), complemento([with, many, 'pro-inflammatory', mediators, which, are, regulated, by, the, nuclear, 'factor-kappaB', '(', 'NF-κB)', family, of, transcription, factors])]). relacion([sujeto(['DNA', sequences, in, these, 'regions,', from, both, unstimulated, or, 'TNF-stimulated', 'PHM1-31', 'cultures,', were]), verbo([associated]), complemento([with, genic, regions, including, 'IκBα,', 'COX-2,', 'IL6RN,', 'Jun', and, 'KCNMB3'])]). relacion([sujeto(['TNF-induced']), verbo([binding]), complemento([events, at, a, consensus, κB, site, numbered, 1667, ;, these, were, represented, by, 112, different, instances, of, the, consensus, κB, motif])]). relacion([sujeto(['In', unstimulated, 'PHM1-31', 'cells,', 'anti-RelA-serum-enriched', regions, were]), verbo([associated]), complemento([with, sequences, corresponding, to, open, reading, frames, of, ion, channel, subunit, genes, including, 'CACNB3', and, 'KCNB1'])]). relacion([sujeto(['Parallel', expression, array, analyses, in, 'PHM1-31', cultures, demonstrated, that, 'TNF']), verbo([stimulated]), complemento([a, &, 'gt;2-fold', induction, in, 51, genes, and, a, fold, repression, of, &, 'gt;1'])]). relacion([sujeto(['We', identified, 14, 'anti-RelA-serum-enriched', genomic, regions, that, correlated, with, 17, 'TNF-inducible', 'genes,', such, as, 'COX2,', 'Egr-1,', 'Jun,', 'IκBα', and, 'IL6,', as, well, as, five, regions]), verbo([associated]), complemento([with, 'TNF-mediated', gene, 'repression,', including, 'Col1A2'])]). relacion([sujeto(['Astrocyte', elevated, 'gene-1', '(', 'AEG-1),', a, novel, human, immunodeficiency, virus, '(', 'HIV)-1', and, tumor, necrosis, factor, '(', 'TNF)-α-inducible', 'oncogene,']), verbo([has]), complemento([generated, significant, interest, in, the, field, of, cancer, research, as, a, therapeutic, target, for, many, metastatic, aggressive, tumors])]). relacion([sujeto(['Immunohistochemical', analyses, of, 'HIV-1', 'Tat', transgenic, mouse, brain, tissues, also, showed, a, marked]), verbo([increase]), complemento([in, 'AEG-1', staining])]). relacion([sujeto(['Similar', to, in, vivo, 'observations,', cultured, astrocytes]), verbo([expressing]), complemento(['HIV-1', 'Tat', also, revealed, 'AEG-1', and, cytokine, 'up-regulation'])]). relacion([sujeto(['Astrocytes', treated, with, 'HAND-relevant', 'stimuli,', 'TNF-α,', interleukin, '(', 'IL)-1β,', and, 'HIV-1,', also, significantly]), verbo([induced]), complemento(['AEG-1', expression, and, nuclear, translocation, via, activation, of, the, nuclear, factor, '(', 'NF)-κB', pathway])]). relacion([sujeto(['AEG-1', knockdown]), verbo([decreased]), complemento(['NF-κB', 'activation,', nuclear, 'translocation,', and, transcriptional, output, in, 'TNF-α-treated', astrocytes])]). relacion([sujeto(['Moreover,', 'IL-1β', treatment, of, 'AEG-1-overexpressing', astrocytes, significantly, lowered, expression, of, excitatory, amino, acid, transporter, 2, ',']), verbo([increased]), complemento([expression, of, excitatory, amino, acid, transporter, 2, repressor, ying, yang, 1, ',', and, reduced, glutamate, 'clearance,', a, major, transducer, of, excitotoxic, neuronal, damage])]). relacion([sujeto(['Peripheral', 'endothelin-1', '(', 'ET-1)', levels, are]), verbo([increased]), complemento([in, chronic, systemic, disorders, such, as, congestive, cardiac, 'failure,', diabetes, and, chronic, renal, failure])]). relacion([sujeto(['Bone', infections, are, also]), verbo([associated]), complemento([with, poor, prognoses, in, these, conditions])]). relacion([sujeto(['In', the, present, 'study,', we, examined, the, alterations, in, 'Toll-like', receptor, 2, '(', 'TLR2)', signaling]), verbo([induced]), complemento([by, 'ET-1', in, an, in, vitro, osteoblast, cell, model])]). relacion([sujeto(['ET-1']), verbo([suppressed]), complemento([cell, surface, expression, of, 'TLR2,', 'NF-κB', phosphorylation, and, 'IL-6', production])]). relacion([sujeto(['As', 'TLR2', represents, an, important, mechanism, by, which, osteoblasts]), verbo([recognize]), complemento([bacterial, 'pathogens,', a, continuously, elevated, 'ET-1', status, may, impair, pathogenic, recognition, by, osteoblasts, and, consequently, affect, bone, metabolism, during, infections])]). relacion([sujeto(['Impairment', of, astrocytic, glutamate, transporter, '(', 'GLT-1;', 'EAAT2)', function, is]), verbo([associated]), complemento([with, multiple, neurodegenerative, 'diseases,', including, 'Parkinson\'s', disease, '(', 'PD)', and, 'manganism,', the, latter, being, induced, by, chronic, exposure, to, high, levels, of, manganese, '(', 'Mn)'])]). relacion([sujeto(['Mn']), verbo([decreases]), complemento(['EAAT2', promoter, activity, and, mRNA, and, protein, 'levels,', but, the, molecular, mechanism, of, 'Mn-induced', 'EAAT2', repression, at, the, transcriptional, level, has, yet, to, be, elucidated])]). relacion([sujeto(['We']), verbo([reveal]), complemento([that, transcription, factor, 'Yin', 'Yang', 1, '(', 'YY1)', is, critical, in, repressing, 'EAAT2', and, mediates, the, effects, of, negative, 'regulators,', such, as, 'Mn', and, tumor, necrosis, factor, alpha, '(', 'TNF-α),', on, 'EAAT2'])]). relacion([sujeto(['YY1', overexpression, in, astrocytes, reduced, 'EAAT2', promoter, 'activity,', while, 'YY1', knockdown, or, mutation, of, the, 'YY1', consensus, site, of, the, 'EAAT2', promoter]), verbo([increased]), complemento([its, promoter, activity, and, attenuated, the, 'Mn-induced', repression, of, 'EAAT2'])]). relacion([sujeto(['Mn']), verbo([increased]), complemento(['YY1', promoter, activity, and, mRNA, and, protein, levels, via, 'NF-κB', activation])]). relacion([sujeto(['This']), verbo([led]), complemento([to, increased, 'YY1', binding, to, the, 'EAAT2', promoter, region])]). relacion([sujeto(['Epigenetically,', histone, deacetylase, '(', 'HDAC)', classes, 'I', and, 'II', served, as, corepressors, of, 'YY1,', 'and,', 'accordingly,', 'HDAC', inhibitors]), verbo([increased]), complemento(['EAAT2', promoter, activity, and, reversed, the, 'Mn-induced', repression, of, 'EAAT2', promoter, activity])]). relacion([sujeto(['Taken', 'together,', our, findings]), verbo([suggest]), complemento([that, 'YY1,', with, 'HDACs', as, 'corepressors,', is, a, critical, negative, transcriptional, regulator, of, 'EAAT2', and, mediates, 'Mn-induced', 'EAAT2', repression])]). relacion([sujeto(['Multiple', 'Myeloma', '(', 'MM)', is, an, incurable, plasma, cell, cancer, that, is]), verbo([caused]), complemento([by, several, chromosomal, translocations, and, gene, deletions])]). relacion([sujeto(['Although', deregulation, of, several, signaling, pathways, including, the, 'Nuclear', 'Factor-Kappa', 'B', '(', 'NF-κB)', pathway]), verbo([has]), complemento([been, reported, in, 'MM,', the, molecular, requirement, and, the, crosstalk, between, 'NF-κB', and, its, target, genes, in, 'MM', cell, survival, has, been, largely, unclear])]). relacion([sujeto(['Here,', we]), verbo([report]), complemento([that, 'Yin', 'Yang1', '(', 'YY1),', a, target, gene, for, 'NF-κB,', is, hyperexpressed, in, most, 'MM', tumor, cells, obtained, from, human, 'patients,', exhibits, constitutive, nuclear, 'localization,', and, is, essential, for, survival, of, 'MM', cells])]). relacion([sujeto(['Mechanistically,', we]), verbo([report]), complemento([a, novel, 'YY1-RelA', complex, 'formation,', which, is, essential, to, transcriptionally, repress, a, proapoptotic, gene, 'Bim'])]). relacion([sujeto(['Moreover,', both, 'YY1', and, 'RelA', are]), verbo([recruited]), complemento([to, the, 'Bim', promoter, and, are, required, to, repress, the, 'Bim', promoter])]). relacion([sujeto(['Importantly,', depletion, of, 'YY1', or, 'RelA', almost, completely, impaired, the, colony, forming, ability, of, 'MM', progenitor, cells]), verbo([suggesting]), complemento([that, both, 'RelA', and, 'YY1', are, essential, for, the, survival, and, growth, of, 'MM', progenitor, cells])]). relacion([sujeto(['Moreover,', depletion, of, either, 'YY1', or, 'RelA', completely]), verbo([inhibited]), complemento(['MM', tumor, growth, in, xenograft, models, for, human, myeloma])]). relacion([sujeto(['Thus,', a, novel, 'RelA-YY1', transcriptional, repression, complex, is, an, attractive, drug]), verbo([target]), complemento([in, 'MM'])]). relacion([sujeto(['Tumor', necrosis, factor, 'receptor-associated', periodic, syndrome, '(', 'TRAPS)', is, an, autosomal, dominant, autoinflammatory, condition]), verbo([caused]), complemento([by, mutations, in, the, 'TNFRSF1A', gene, which, encodes, the, tumor, necrosis, factor, '(', 'TNF)', 'receptor,', 'TNFR1'])]). relacion([sujeto(['Interestingly,', high, p65, activity, was]), verbo([associated]), complemento([with, elevated, 'IL-8', 'secretion,', whereas, high, 'c-Rel', activity, increased, 'IL-1β', and, 'IL-12', secretion])]). relacion([sujeto(['In', 'conclusion,', while, all, six, 'TNFRSF1A', mutations, showed]), verbo([enhanced]), complemento(['NF-κB', 'activity,', different, mutations, stimulated, distinct, 'NF-κB', family, subunit, 'activities,', and, this, in, turn, resulted, in, the, generation, of, unique, cytokine, secretory, profiles])]). relacion([sujeto(['Pancreatic', mRNA, expression, of, 'cytokines,', the, monocyte, chemoattractant, 'protein,', and, 'GLUT2', were, evaluated, as, well, as, pancreas]), verbo([nuclear]), complemento([factor, '(', 'NF)-κB', p65, and, inhibitor, of, κB, '(', 'IκB)', protein, expression])]). relacion([sujeto(['STZ-induced', 'fat-1', mice, did, not, develop, hyperglycemia, compared, with, 'wild-type', 'mice,', and, 'β-cell', destruction, was]), verbo([prevented]), complemento([as, evidenced, by, lack, of, histological, pancreatic, damage, or, reduced, insulin, level])]). relacion([sujeto(['The', prevention, of, 'β-cell', destruction, was]), verbo([associated]), complemento([with, no, proinflammatory, cytokine, induction, '(', tumor, necrosis, 'factor-α,', 'interleukin-1β,', inducible, nitric, oxide, 'synthase)', in, the, 'pancreas,', a, decreased, 'NF-κB,', and, increased, 'IκB', pancreatic, protein, expression])]). relacion([sujeto(['In', the, 'fat-1-treated', 'mice,', proinflammatory, 'arachidonic-derived', mediators, as, prostaglandin, 'E₂', and, 12, -, hydroxyeicosatetraenoic, acid, were]), verbo([decreased]), complemento([and, the, 'anti-inflammatory', lipoxin, 'A₄', was, detected])]). relacion([sujeto(['Ubiquitin', 'carboxyl-terminal', hydrolase, 'L1', '(', 'UCH-L1)', is, a, deubiquitinating, enzyme, that, plays, a, regulatory, role, in]), verbo([targeting]), complemento([proteins, for, proteasomal, degradation])]). relacion([sujeto(['UCH-L1', is, highly]), verbo([expressed]), complemento([in, neurons, and, has, been, demonstrated, to, promote, cell, viability, and, maintain, neuronal, integrity])]). relacion([sujeto(['Reduced', 'UCH-L1', levels]), verbo([have]), complemento([been, observed, in, various, neurodegenerative, 'diseases,', and, expression, of, 'UCH-L1', can, rescue, synaptic, dysfunction, and, memory, deficits, in, 'Alzheimer\'s', 'Disease', model, mice])]). relacion([sujeto(['However,', the, mechanisms]), verbo([regulating]), complemento(['UCH-L1', expression, have, not, been, determined])]). relacion([sujeto(['Expression', of, 'NF-κB']), verbo([suppressed]), complemento(['UCH-L1', gene, transcription])]). relacion([sujeto(['Furthermore,', activation, of, 'NF-κB', signaling, by, the, inflammatory, stimulator, lipopolysaccharide, and, 'TNFα', resulted, in, a]), verbo([decrease]), complemento([of, 'UCH-L1', gene, expression, by, inhibiting, its, transcription])]). relacion([sujeto(['As', 'NF-κB', is, an, important, signaling, module, in, inflammatory, 'response,', our, study]), verbo([suggests]), complemento([a, possibility, that, inflammation, might, compromise, neuronal, functions, via, the, interaction, of, 'NF-κB', and, 'UCH-L1'])]). relacion([sujeto(['A', better, understanding, of, the, 'NF-κB-regulated', 'UCH-L1', transcription, will]), verbo([provide]), complemento([insights, to, the, role, of, inflammatory, responses, in, 'Alzheimer\'s', disease, and, 'Parkinson\'s', disease])]). relacion([sujeto(['Bone', morphogenetic, proteins, '(', 'BMPs)']), verbo([induce]), complemento([not, only, bone, formation, in, vivo, but, also, osteoblast, differentiation, of, mesenchymal, cells, in, vitro])]). relacion([sujeto(['Tumor', necrosis, factor, alpha, '(', 'TNFalpha)']), verbo([inhibits]), complemento([both, osteoblast, differentiation, and, bone, formation, induced, by, 'BMPs'])]). relacion([sujeto(['In', this, 'study,', we]), verbo([found]), complemento([that, 'TNFalpha', inhibited, the, alkaline, phosphatase, activity, and, markedly, reduced, 'BMP2-', and, 'Smad-induced', reporter, activity, in, 'MC3T3-E1', cells])]). relacion([sujeto(['TNFalpha', had, no, effect, on, the, phosphorylation, of, 'Smad1,', 'Smad5,', and, 'Smad8', or, on, the]), verbo([nuclear]), complemento([translocation, of, the, 'Smad1-Smad4', complex])]). relacion([sujeto(['In', 'p65-deficient', mouse, embryonic, 'fibroblasts,', overexpression, of, 'p65,', a, subunit, of, 'NF-kappaB,']), verbo([inhibited]), complemento(['BMP2-', and, 'Smad-induced', reporter, activity, in, a, 'dose-dependent', manner])]). relacion([sujeto(['Although', 'TNFalpha', failed, to, affect, 'receptor-dependent', formation, of, the, 'Smad1-Smad4', 'complex,', p65]), verbo([associated]), complemento([with, the, complex])]). relacion([sujeto(['Chromatin', immunoprecipitation, and, electrophoresis, mobility, shift, assays, revealed, that, 'TNFalpha']), verbo([suppressed]), complemento([the, 'DNA', binding, of, 'Smad', proteins, to, the, target, gene])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, 'TNFalpha', inhibits, 'BMP', signaling, by, interfering, with, the, 'DNA', binding, of, 'Smads', through, the, activation, of, 'NF-kappaB'])]). relacion([sujeto(['Analysis', of, the, microarray, data, indicated, that, copper]), verbo([modulates]), complemento([multiple, signal, transduction, 'pathways,', including, those, mediated, by, 'NF-kappaB'])]). relacion([sujeto(['Luciferase', 'assays,', quantitative, reverse, transcription, 'real-time', 'PCR,', and, chemical, inhibition, in, 'HepG2', cells, validated, the, microarray, results, and, confirmed, that, 'NF-kappaB', was]), verbo([activated]), complemento([by, 'stress-inducible', concentrations, of, copper])]). relacion([sujeto(['In', the, past, few, 'decades,', the, use, of, natural, 'compounds,', such, as, 'flavonoids,', as, 'anti-inflammatory', agents]), verbo([has]), complemento([gained, much, attention])]). relacion([sujeto(['Treatment', of, 'RINm5F', '(', 'RIN)', rat, insulinoma, cells, with, interleukin, 1, beta, '(', 'IL-1beta)', and, interferon, gamma, '(', 'IFN-gamma)']), verbo([induced]), complemento([cell, damage])]). relacion([sujeto(['Incubation', with, 'quercetin,', 'apigenin,', and, luteolin, resulted, in, a, significant, reduction, in, 'IL-1beta-', and, 'IFN-gamma-induced', nitric, oxide, 'production,', a]), verbo([finding]), complemento([that, correlated, well, with, reduced, levels, of, the, inducible, form, of, 'NO', synthase, messenger, 'RNA', and, protein])]). relacion([sujeto(['The', molecular, mechanism, by, which, 'quercetin,', 'apigenin,', and, luteolin]), verbo([inhibited]), complemento([inducible, 'NO', synthase, gene, expression, appeared, to, involve, the, inhibition, of, nuclear, factor, kappaB, '(', 'NF-kappaB)', activation])]). relacion([sujeto(['The', 'IL-1beta-', and, 'IFN-gamma-stimulated', 'RIN', cells, showed]), verbo([increases]), complemento([in, 'NF-kappaB', binding, 'activity,', p50, and, p65, subunit, levels, in, 'nucleus,', and, 'IkappaB', alpha, degradation, in, cytosol, compared, with, unstimulated, cells])]). relacion([sujeto(['Quercetin,', 'apigenin,', and, luteolin, also]), verbo([prevented]), complemento(['IL-1beta-', and, 'IFN-gamma-mediated', inhibition, of, insulin, secretion])]). relacion([sujeto(['Quercetin,', 'apigenin,', and, luteolin]), verbo([inhibited]), complemento([cytotoxicity, in, 'RIN', cells, and, attenuated, the, decrease, of, 'glucose-stimulated', insulin, secretion, in, islets, by, 'IL-1beta', and, 'IFN-gamma'])]). relacion([sujeto(['OX40', is, a, member, of, the, 'TNFR', superfamily, '(', 'CD134;', 'TNFRSF4)', that, is]), verbo([expressed]), complemento([on, activated, 'T', cells, and, regulates, 'T', 'cell-mediated', immune, responses])]). relacion([sujeto(['In', this, 'study,', we]), verbo([have]), complemento([examined, the, regulation, of, 'OX40', gene, expression, in, 'T', cells])]). relacion([sujeto(['We']), verbo([have]), complemento([shown, in, this, study, that, basal, 'OX40', promoter, activity, is, regulated, by, constitutively, expressed, 'Sp1/Sp3', and, 'YY1', transcription, factors])]). relacion([sujeto(['NF-kappaB', '(', p50, and, 'p65)', also]), verbo([binds]), complemento([to, the, 'OX40', promoter, 'region,', but, the, level, of, direct, enhancement, of, the, 'OX40', promoter, activity, by, this, transcription, factor, is, not, sufficient, to, account, for, the, observed, 'up-regulation', of, 'OX40', mRNA, expression, associated, with, activation])]). relacion([sujeto(['We']), verbo([have]), complemento([detected, by, chromatin, immunoprecipitation, that, histone, 'H4', molecules, in, the, 'OX40', promoter, region, are, highly, acetylated, by, activation, and, 'NF-kappaB', binds, to, the, 'OX40', promoter, in, vivo])]). relacion([sujeto(['These', findings]), verbo([suggest]), complemento([that, 'OX40', gene, expression, is, regulated, by, chromatin, 'remodeling,', and, that, 'NF-kappaB', might, be, involved, in, initiation, of, chromatin, remodeling, in, the, 'OX40', promoter, region, in, activated, 'T', cells])]). relacion([sujeto(['CD4(+)CD25(+)', regulatory, 'T', '(', 'Treg)', cells, also]), verbo([express]), complemento(['OX40', at, high, 'levels,', and, signaling, through, this, receptor, can, neutralize, suppressive, activity, of, this, 'Treg', cell])]). relacion([sujeto(['To']), verbo([gain]), complemento([insight, into, these, 'mechanisms,', gene, expression, profiling, was, examined, in, 'C2C12', myoblasts, devoid, of, 'NF-kappaB', activity])]). relacion([sujeto(['Interestingly,', even, in, proliferating, 'myoblasts,', the, absence, of, 'NF-kappaB']), verbo([caused]), complemento([the, pronounced, induction, of, several, myofibrillar, 'genes,', suggesting, that, 'NF-kappaB', functions, as, a, negative, regulator, of, 'late-stage', muscle, differentiation])]). relacion([sujeto(['Although', several, myofibrillar, promoters, contain, predicted, 'NF-kappaB']), verbo([binding]), complemento(['sites,', functional, analysis, using, the, 'troponin-I2', gene, as, a, model, revealed, that, 'NF-kappaB-mediated', repression, does, not, occur, through, direct, 'DNA', binding])]). relacion([sujeto(['While', inducers, of, 'NF-kappaB']), verbo([stimulated]), complemento(['YY1', expression, in, multiple, cell, 'types,', genetic, ablation, of, the, 'RelA/p65', subunit, of, 'NF-kappaB', in, both, cultured, cells, and, adult, skeletal, muscle, correlated, with, reduced, 'YY1', transcripts, and, protein])]). relacion([sujeto(['NF-kappaB', regulation, of, 'YY1', occurred, at, the, transcriptional, 'level,']), verbo([mediated]), complemento([by, direct, binding, of, the, 'p50/p65', heterodimer, complex, to, the, 'YY1', promoter])]). relacion([sujeto(['Furthermore,', 'YY1', was]), verbo([found]), complemento([associated, with, multiple, myofibrillar, promoters, in, 'C2C12', myoblasts, containing, 'NF-kappaB', activity])]). relacion([sujeto(['Based', on, these, 'results,', we, propose, that, 'NF-kappaB', regulation, of, 'YY1', and, transcriptional, silencing, of, myofibrillar, genes, represent, a, new, mechanism, by, which, 'NF-kappaB', functions, in, myoblasts, to]), verbo([modulate]), complemento([skeletal, muscle, differentiation])]). relacion([sujeto(['Activation', of, the, transcriptional, factor, 'NF-kappaB', is]), verbo([triggered]), complemento([by, 'signal-dependent', degradation, of, its, inhibitor, protein, 'IkappaB', through, the, ubiquitin, '(', 'Ub)-proteasome', pathway])]). relacion([sujeto(['We']), verbo([found]), complemento([here, that, a, phosphorylated, 'IkappaBalpha', immunoprecipitated, '(', 'IP-pIkappaBalpha)', from, the, crude, extract, of, 'HeLa', cells, which, had, been, treated, with, tumor, necrosis, 'factor-alpha', '(', 'TNFalpha)', caused, a, dramatic, ubiquitination, of, 'itself,', termed, 'autoubiquitination,', when, incubated, with, 'ATP,', 'Ub,', and, 'E1-activating', and, 'E2-conjugating', enzymes])]). relacion([sujeto(['IP-pIkappaBalpha', also, catalyzed, ubiquitination, of, an, in, vitro, synthesized, 35, 'S-IkappaBalpha', previously]), verbo([phosphorylated]), complemento([by, 'IkappaB-kinase', '(', 'IKK)', which, is, referred, to, as, transubiquitination])]). relacion([sujeto(['Moreover,', the, putative, 'IkappaBalpha-Ub', ligase, '(', 'IkappaBalpha-E3)', present, in, 'HeLa', cell, cytosol]), verbo([associated]), complemento([in, vitro, with, an, 'IKK-phosphorylated', recombinant, 'IkappaBalpha,', a, process, independent, of, 'NF-kappaB', binding, to, 'IkappaBalpha', or, 'TNFalpha', stimulation])]). relacion([sujeto(['Replacement', of, the, two, 'Ser', residues, at, positions, 32, and, 36, corresponding, to, 'IKK', phosphorylation, sites, by, 'Ala', resulted, in, almost, complete, prevention, of]), verbo([binding]), complemento([of, an, 'IkappaBalpha-E3', to, 'IkappaBalpha'])]). relacion([sujeto(['These', results, indicate, that, phosphorylation, of, 'IkappaBalpha', is, necessary, and, sufficient, for, recruitment, of, this, 'IkappaBalpha-E3', to]), verbo([associate]), complemento([with, 'IkappaBalpha'])]). relacion([sujeto(['These', mice]), verbo([have]), complemento([thyrotrope, hypertrophy, and, hyperplasia, and, develop, thyrotrope, adenoma])]). relacion([sujeto(['We']), verbo([report]), complemento([that, cell, proliferation, is, 'increased,', but, the, expression, of, most, stem, cell, markers, is, unchanged])]). relacion([sujeto(['The', 'α-subunit', is]), verbo([required]), complemento([for, secretion, of, the, glycoprotein, hormone, 'β-subunits,', and, mutants, exhibit, elevated, expression, of, many, genes, involved, in, the, unfolded, protein, 'response,', consistent, with, dilation, and, stress, of, the, endoplasmic, reticulum])]). relacion([sujeto(['Mutants']), verbo([have]), complemento([elevated, expression, of, transcription, factors, that, are, important, in, thyrotrope, 'function,', such, as, 'Gata2', and, 'Islet', 1, ',', and, those, that, stimulate, 'proliferation,', including, 'Nupr1,', 'E2f1,', and, 'Etv5'])]). relacion([sujeto(['Stable', expression, of, 'Tceal5', in, a, pituitary, progenitor, cell, line, is, sufficient, to]), verbo([increase]), complemento([cell, proliferation])]). relacion([sujeto(['Thus,', 'Tceal5', may]), verbo([act]), complemento([as, a, 'proto-oncogene'])]). relacion([sujeto(['This', study]), verbo([provides]), complemento([a, rich, resource, for, comparing, pituitary, transcriptomes, and, an, analysis, of, gene, expression, networks])]). relacion([sujeto(['Genome-wide', association, studies, '(', 'GWAS)']), verbo([have]), complemento([prioritized, a, transcription, 'factor,', nuclear, receptor, 2, family, 2, '(', 'NR2F2),', as, being, associated, with, essential, hypertension, in, humans])]). relacion([sujeto(['Here', we]), verbo([provide]), complemento([evidence, that, validates, this, association, and, indicates, that, 'Nr2f2', is, a, genetic, determinant, of, blood, pressure, '(', 'BP)'])]). relacion([sujeto(['Using', the, 'zinc-finger', nuclease, 'technology,', the, generation, of, a]), verbo([targeted]), complemento(['Nr2f2-edited', rat, model, is, reported])]). relacion([sujeto(['The', resulting, 'gene-edited', rats]), verbo([have]), complemento([a, 15, bp, deletion, in, exon, 2, leading, to, a, 'five-amino-acid', deletion, in, the, hinge, region, of, the, mutant, 'Nr2f2', protein])]). relacion([sujeto(['Because', the, hinge, region, of, 'Nr2f2', is]), verbo([required]), complemento([for, interaction, with, 'Friend', of, 'Gata2', '(', 'Fog2),', 'protein-protein', interaction, is, examined])]). relacion([sujeto(['Here,', we, show, that, a, combinatorial, interaction, between, the, bHLH, transcription, factors, 'Ascl1', and, 'Helt', is]), verbo([required]), complemento([for, acquiring, thalamic, progenitor, identity])]). relacion([sujeto(['Furthermore,', we, show, that, the, prethalamic, factors, 'Dlxs', upregulated, by, 'Ascl1/Helt', deficiency, play, unique, roles, in]), verbo([regulating]), complemento([thalamic, progenitor, 'specification,', and, that, derepression, of, 'Dlx2', and, 'Dlx5', suppress, generation, of, 'TH-R', neurons])]). relacion([sujeto(['Taken', 'together,', our, results]), verbo([suggest]), complemento([a, model, whereby, the, combined, activity, of, two, distinct, bHLH, factors, plays, a, key, role, in, the, development, of, discrete, classes, of, thalamic, interneurons])]). relacion([sujeto(['However,', the, nucleic, acid, secondary, and, tertiary, structure, can, also]), verbo([act]), complemento([as, a, recognition, site, for, the, transcription, factor, in, a, process, known, as, indirect, 'read-out,', although, this, is, much, less, understood])]). relacion([sujeto(['We']), verbo([have]), complemento([previously, identified, such, a, transcriptional, control, mechanism, in, early, 'Xenopus', development, where, the, interaction, of, the, transcription, factor, ilf3, and, the, gata2, promoter, requires, the, presence, of, both, an, unusual, 'A-form', 'DNA', structure, and, a, 'CCAAT', sequence])]). relacion([sujeto(['Rapid', identification, of, such, promoters, elsewhere, in, the, 'Xenopus', and, other, genomes, would]), verbo([provide]), complemento([insight, into, a, less, studied, area, of, gene, 'regulation,', although, currently, there, are, few, tools, to, analyse, genomes, in, such, ways])]). relacion([sujeto(['In', this, paper, we]), verbo([report]), complemento([the, implementation, of, a, novel, bioinformatics, approach, that, has, identified, 86, such, putative, promoters, in, the, 'Xenopus', genome])]). relacion([sujeto(['We']), verbo([have]), complemento([shown, that, five, of, these, sites, are, 'A-form', in, 'solution,', bind, to, transcription, factors, and, fully, validated, one, of, these, newly, identified, promoters, as, interacting, with, the, ilf3, containing, complex, 'CBTF'])]). relacion([sujeto(['This', interaction]), verbo([regulates]), complemento([the, transcription, of, a, previously, uncharacterised, downstream, gene, that, is, active, in, early, development])]). relacion([sujeto(['A', 'Perl', program, '(', 'APTE)']), verbo([has]), complemento([located, a, number, of, potential, 'A-form', 'DNA', promotor, elements, in, the, 'Xenopus', 'genome,', five, of, these, putative, targets, have, been, experimentally, validated, as, 'A-form', and, as, targets, for, specific, 'DNA', binding, 'proteins;', one, has, also, been, shown, to, interact, with, the, 'A-form', binding, transcription, factor, ilf3])]). relacion([sujeto(['In', addition, to]), verbo([providing]), complemento([energy, and, constituting, cell, 'membrane,', fatty, acids, also, play, an, important, role, in, adipocyte, differentiation, and, lipid, metabolism])]). relacion([sujeto(['As', an, important, member, of, monounsaturated, fatty, 'acids,', 'oleate,', together, with, other, 'components,', is, widely, used, to]), verbo([induce]), complemento([chicken, preadipocyte, differentiation])]). relacion([sujeto(['However,', it, is, not, clear, whether, oleate, alone, can]), verbo([induce]), complemento([chicken, preadipocyte, differentiation])]). relacion([sujeto(['After', treatment, of, oleate, on, chicken, 'preadipocytes,', apparent, lipid, droplet, formation, and, lipid, accumulation, were, 'observed,', accompanied, by]), verbo([increasing]), complemento([expression, of, peroxisome, 'proliferator-activated', 'receptor-γ', '(', 'PPARγ)', and, adipocyte, fatty, 'acid-binding', protein, '(', 'AFABP),', but, decreasing, level, of, 'GATA', binding, protein, 2, '(', 'GATA2)'])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, exogenous, oleate, alone, can, act, as, an, inducer, of, preadipocyte, differentiation, into, adipocytes])]). relacion([sujeto(['Lymphedema', is]), verbo([caused]), complemento([by, dysfunction, of, lymphatic, 'vessels,', leading, to, disabling, swelling, that, occurs, mostly, on, the, extremities])]). relacion([sujeto(['Nine', mutated, genes]), verbo([have]), complemento([been, identified, in, different, isolated, or, syndromic, forms, of, lymphedema])]). relacion([sujeto(['Twelve', mutations, were]), verbo([found]), complemento([that, explain, 8, '%', of, the, cases])]). relacion([sujeto(['Still', unidentified, is, the, genetic]), verbo([cause]), complemento([of, primary, lymphedema, in, 64, '%', of, patients, with, a, family, history, and, 92, '%', of, sporadic, cases])]). relacion([sujeto(['Interestingly,', most, of, the, proteins, that, are, encoded, by, the, genes, mutated, in, primary, lymphedema, seem, to]), verbo([act]), complemento([in, a, single, functional, pathway, involving, 'VEGFR3', signaling])]). relacion([sujeto(['This', underscores, the, important, role, this, pathway, plays, in, lymphatic, development, and, function, and]), verbo([suggests]), complemento([that, the, unknown, genes, also, have, a, role])]). relacion([sujeto(['The', 'MED1', subunit, of, the, 'Mediator', transcriptional, coregulator, complex, is, a]), verbo([nuclear]), complemento(['receptor-specific', coactivator])]). relacion([sujeto(['A', negative, feedback, mechanism, of, 'thyroid-stimulating', hormone, '(', 'TSH,', or, 'thyrotropin)', expression, in, the, thyrotroph, in, the, presence, of, triiodothyronine, '(', 'T3)', is, employed, by, liganded, thyroid, hormone, receptor, β, '(', 'TRβ)', on, the, 'TSHβ', gene, 'promoter,', where, conventional, 'histone-modifying', coactivators]), verbo([act]), complemento([as, corepressors])]). relacion([sujeto(['We', now]), verbo([provide]), complemento([evidence, that, 'MED1', is, a, 'ligand-dependent', positive, cofactor, on, this, promoter])]). relacion([sujeto(['TSHβ', gene, transcription, was, attenuated, in, 'MED1', mutant, mice, in, which, the]), verbo([nuclear]), complemento(['receptor-binding', ability, of, 'MED1', was, specifically, disrupted])]). relacion([sujeto(['MED1']), verbo([stimulated]), complemento(['GATA2-', and, 'Pit1-mediated', 'TSHβ', gene, promoter, activity, in, a, 'ligand-independent', manner, in, cultured, cells])]). relacion([sujeto(['MED1', also]), verbo([stimulated]), complemento([transcription, from, the, 'TSHβ', gene, promoter, in, a, 'T3-dependent', manner])]). relacion([sujeto(['The', transcription, was, further]), verbo([enhanced]), complemento([when, the, 'T3-dependent', corepressors, 'SRC1,', 'SRC2,', and, 'HDAC2', were, downregulated])]). relacion([sujeto(['Pituitary', adenylate, 'cyclase-activating', polypeptide, 1, '(', 'PACAP', or, 'ADCYAP1)']), verbo([regulates]), complemento([gonadotropin, biosynthesis, and, 'secretion,', both, alone, and, in, conjunction, with, 'GNRH'])]). relacion([sujeto(['Initially', identified, as, a, 'hypothalamic-releasing', 'factor,', 'ADCYAP1', subsequently]), verbo([has]), complemento([been, identified, in, pituitary, 'gonadotropes,', suggesting, it, may, act, as, an, 'autocrine-paracrine', factor, in, this, tissue])]). relacion([sujeto(['GNRH']), verbo([has]), complemento([been, shown, to, increase, pituitary, 'Adcyap1', gene, expression, through, the, interaction, of, 'CREB', and, 'jun/fos', with, 'CRE/AP1', 'cis-elements', in, the, proximal, promoter])]). relacion([sujeto(['In', these, 'studies,', we, were, interested, in, identifying, additional, transcription, factors, and, cognate, 'cis-elements', which]), verbo([regulate]), complemento(['Adcyap1', gene, promoter, activity, and, chose, to, focus, on, the, 'GATA', family, of, transcription, factors, known, to, be, critical, for, both, pituitary, cell, differentiation, and, gonadotropin, subunit, expression])]). relacion([sujeto(['By', transient, transfection, and, electrophoretic, mobility, shift, assay, 'analysis,', we, demonstrate, that, 'GATA2', and, 'GATA4']), verbo([stimulate]), complemento(['Adcyap1', promoter, activity, via, a, 'GATA', 'cis-element', located, at, position, -, 191, in, the, rat, 'Adcyap1', gene, promoter])]). relacion([sujeto(['Conversely,', blunting, 'GATA', expression, with, specific, siRNA]), verbo([inhibits]), complemento([the, ability, of, 'GNRH', to, stimulate, 'ADCYAP1', mRNA, levels, in, these, cells])]). relacion([sujeto(['These', data, demonstrate, a, complex, interaction, between, 'GNRH', and, 'GATA', on, 'ADCYAP1', 'expression,']), verbo([providing]), complemento([important, new, insights, into, the, regulation, of, gonadotrope, function])]). relacion([sujeto(['We', show, that, 'VEGFA', produced, in, the, somites, is]), verbo([required]), complemento([to, initiate, adult, haemangioblast, programming, in, the, adjacent, 'DLP', by, establishing, endogenous, 'VEGFA', signalling])]). relacion([sujeto(['Scl', activation]), verbo([requires]), complemento([synergy, between, this, 'VEGFA-controlled', pathway, and, a, 'VEGFA-independent', pathway, controlled, by, 'Fli1,', 'Gata2', and, 'Etv2/Etsrp/ER71,', which, also, drives, expression, of, the, 'Scl', partner, 'Lmo2'])]). relacion([sujeto(['Furthermore,', 'Gata2', is, initially]), verbo([activated]), complemento([by, 'Fli1', but, later, maintained, by, another, 'ETS', 'factor,', 'Etv2'])]). relacion([sujeto(['We', also, establish, that, 'Flk1', and, 'Etv2']), verbo([act]), complemento([independently, in, the, two, pathways, to, 'Scl', activation])]). relacion([sujeto(['Thus,', detailed, 'temporal,', epistatic, measurements, of, key, 'TFs', and, 'VEGFA', plus, its, receptor]), verbo([have]), complemento([enabled, us, to, build, a, 'Xenopus', adult, haemangioblast, 'GRN'])]). relacion([sujeto(['Here', we, show, that, the, transcription, factor, 'Gata2', is]), verbo([expressed]), complemento([anteriorly, before, this, stage])]). relacion([sujeto(['However,', although, 'Vg1', is]), verbo([required]), complemento([for, streak, 'formation,', 'Gata2', does, not, act, as, an, absolute, anterior, 'specifier,', but, provides, an, anterior, bias])]). relacion([sujeto(['EVI1', is, a, member, of, a, group, of, transcription, factors, with, 'C-terminal']), verbo([binding]), complemento([protein, '(', 'CtBP)-binding', motifs, that, act, as, transcriptional, 'co-repressors;', 'however,', we, recently, found, that, 'EVI1', directly, activates, 'GATA2', 'transcription,', which, is, an, important, gene, for, the, maintenance, of, hematopoietic, stem, cells])]). relacion([sujeto(['We', show, here, that, 'EVI1-activated', 'GATA2', transcripts, derive, from, exon, 1, 'S', of, 'GATA2,', which, is, specifically]), verbo([activated]), complemento([in, neural, and, hematopoietic, cells])]). relacion([sujeto(['Acetylation', at, 'Lys(564),', which, is, adjacent, to, the, 'CtBP-binding', consensus, sequence, of, 'EVI1,', was]), verbo([found]), complemento([to, be, important, for, transcriptional, activation, of, 'GATA2'])]). relacion([sujeto(['Mutation', of, 'Lys(564)', to, alanine, '(', 'K564A)', markedly, reduced, the, ability, of, 'EVI1', to]), verbo([bind]), complemento(['DNA', and, activate, transcription, of, 'GATA2'])]). relacion([sujeto(['Thus,', acetylation, of, 'EVI1', at, 'Lys(564)', by, 'P/CAF']), verbo([enhances]), complemento([the, 'DNA', binding, capacity, of, 'EVI1', and, thereby, contributes, to, the, activation, of, 'GATA2'])]). relacion([sujeto(['A', 'T', &, 'gt;', 'C', transition, occurring, in, the, second, repeat, of, each, 'VNTR', allele, implies, the, 'presence/absence', of, a, putative, 'GATA']), verbo([binding]), complemento([motif])]). relacion([sujeto(['Aims', of, the, present, study, 'were:', 1, ')', to, verify, if, 'GATA', and, 'AP-1', sites, could]), verbo([bind]), complemento(['GATA2', and, 'c-Jun/c-Fos', 'factors,', 'respectively;', 2, ')', to, investigate, whether, such, sites, modulate, the, enhancer, activity, of, the, 'SIRT3-VNTR', alleles])]). relacion([sujeto(['DAPA', assay, proved, that, 'GATA2', and, 'c-Jun/c-Fos', factors, are, able, to]), verbo([bind]), complemento([the, corresponding, sites])]). relacion([sujeto(['Furthermore,', we, established, that, 'GATA2', and, 'c-Jun/c-Fos']), verbo([act]), complemento([additively, in, modulating, the, 'SIRT3-VNTR', enhancer, function])]). relacion([sujeto(['Clenbuterol']), verbo([increased]), complemento([the, size, of, both, fast, and, slow, fibers, in, utero, which, was, associated, with, a, decreased, 'DNA:protein', ratio, '(', 28, '%', ')', and, an, increased, 'RNA:DNA', ratio, '(', 36, '%', ')'])]). relacion([sujeto(['Additionally,', drug, treatment, in, utero]), verbo([induced]), complemento([a, decrease, in, the, 'fast:slow', fiber, ratio, '(', 38, '%', ')'])]). relacion([sujeto(['These', myogenic, changes, were, correlated, with, an]), verbo([increase]), complemento([in, the, 'GATA-2', hypertrophic, transcription, factor, at, both, 17.5, dg, '(', by, 250, '%', ')', and, 19.5, dg, '(', by, 40, '%', ')', in, fetuses, from, clenbuterol, treated, dams])]). relacion([sujeto(['In', 'addition,', drug, treatment, resulted, in]), verbo([increased]), complemento([membrane, association, of, 'PKC-micro', at, 17.5, dg, '(', 325, '%', ')', and, increased, 'PKC-alpha', cytosolic, abundance, '(', 40, '%', ')', and, 'PKC-theta', membrane, abundance, at, 19.5, dg, '(', 250, '%', ')'])]). relacion([sujeto(['These', results, are, the, first, demonstration, that, 'beta(2)-agonists', such, as, clenbuterol, may]), verbo([act]), complemento([through, upregulating, the, 'GATA-2', transcription, factor, and, implicate, certain, 'PKC', isoforms, in, the, 'drug-induced', regulation, of, skeletal, muscle, development])]). relacion([sujeto(['Mediator', '(', 'MED)', 220, /, thyroid, 'receptor-associated', protein, '(', 'TRAP)', 220, is, a, transcriptional, mediator, that]), verbo([interacts]), complemento([with, liganded, 'thyroid/steroid', hormone, receptors])]). relacion([sujeto(['MED220', haploinsufficient, heterozygotes, exhibited, hypothyroidism, and, reduced, 'TSHbeta', 'transcripts,']), verbo([suggesting]), complemento([a, specific, function, for, 'TSHbeta', transcription])]). relacion([sujeto(['We', previously, demonstrated, that, 'Pit-1', and, 'GATA-2', can]), verbo([bind]), complemento([to, a, composite, element, within, the, proximal, 'TSHbeta', promoter, and, synergistically, activate, transcription])]). relacion([sujeto(['Cotransfections', in, 'CV-1', cells, showed, that, 'Pit-1,', 'GATA-2,', or, 'MED220', alone, did, not, markedly]), verbo([stimulate]), complemento([the, 'TSHbeta', promoter])]). relacion([sujeto(['Glutathione-S-transferase', interaction, studies, showed, that, 'MED220', or, 'GATA-2', each]), verbo([bound]), complemento([the, homeodomain, of, 'Pit-1,', whereas, 'MED220', interacted, independently, with, each, zinc, finger, of, 'GATA-2', but, not, with, either, terminus])]). relacion([sujeto(['MED220']), verbo([interacted]), complemento([with, 'GATA-2', and, 'Pit-1', over, a, broad, region, of, its, 'N', terminus])]). relacion([sujeto(['Coimmunoprecipitation', confirmed, that, all, three, factors, can]), verbo([interact]), complemento([in, thyrotropes, and, chromatin, immunoprecipitation, demonstrated, in, vivo, occupancy, on, the, proximal, 'TSHbeta', promoter])]). relacion([sujeto(['Thus,', the, 'TSHbeta', gene, is, maximally]), verbo([activated]), complemento([by, a, combination, of, three, thyrotrope, transcription, factors, that, act, via, both, 'protein-DNA', and, 'protein-protein', interactions])]). relacion([sujeto(['The', transcription, factors, 'c-myb', and, 'GATA-2', are, both]), verbo([required]), complemento([for, blood, cell, development, in, vivo, and, in, vitro])]). relacion([sujeto(['We']), verbo([report]), complemento([here, that, embryonic, stem, '(', 'ES)', cells, transfected, with, 'c-myb', or, 'GATA-2', 'cDNAs,', individually, or, in, 'combination,', underwent, hematopoietic, commitment, and, differentiation, in, the, absence, of, added, hematopoietic, growth, factors, but, that, stimulation, with, 'c-kit', and, 'flt-3', ligands, enhanced, colony, formation, only, in, the, 'c-myb', transfectants])]). relacion([sujeto(['Transfection', of, 'ES', cells, with, either, a, 'c-myb', or, a, 'GATA-2', antisense, construct, abrogated, erythromyeloid, 'colony-forming', ability, in, methyl, 'cellulose;', 'however,', introduction, of, a, 'full-length', 'GATA-2', or, 'c-myb', 'cDNA,', 'respectively,', rescued, the, 'hematopoiesis-deficient', 'phenotype,', although, only, 'c-myb-rescued', 'ES', cells]), verbo([expressed]), complemento(['c-kit', and, 'flt-3', surface, receptors, and, formed, increased, numbers, of, hematopoietic, colonies, upon, stimulation, with, the, cognate, ligands])]). relacion([sujeto(['Of', greater, 'importance,', our, studies]), verbo([suggest]), complemento([that, 'GATA-2', and, 'c-myb', exert, their, roles, in, hematopoietic, gene, regulation, through, distinct, mechanisms, of, action, in, nonoverlapping, pathways])]). relacion([sujeto(['Beyond', 'enumeration,', circulating, tumor, cells, '(', 'CTCs)', can]), verbo([provide]), complemento([genetic, information, from, metastatic, cancer, that, may, facilitate, a, greater, understanding, of, tumor, biology, and, enable, a, precision, medicine, approach])]). relacion([sujeto(['We', compiled, copy]), verbo([gains]), complemento([and, 'losses,', with, a, particular, focus, on, those, genes, highly, implicated, in, mCRPC, progression, and, previously, validated, as, being, aberrant, in, metastatic, tissue, samples, and, genomic, studies, of, reference, mCRPC, datasets])]). relacion([sujeto(['Genomic']), verbo([gains]), complemento([in, &, 'gt;25%', of, 'CTCs', were, observed, in, 'AR,', 'FOXA1,', 'ABL1,', 'MET,', 'ERG,', 'CDK12,', 'BRD4,', and, 'ZFHX3,', while, common, genomic, losses, involved, 'PTEN,', 'ZFHX3,', 'PDE4DIP,', 'RAF1,', and, 'GATA2'])]). relacion([sujeto(['Analysis', of, aCGH, in, a, sample, with, sequential, enzalutamide, resistant, visceral, progression, showed, acquired]), verbo([loss]), complemento([of, 'AR', amplification, concurrent, with, gain, of, 'MYCN,', consistent, with, evolution, toward, a, 'neuroendocrine-like,', 'AR-independent', clone])]). relacion([sujeto(['Genomic', analysis, of, pooled, 'CTCs', in, men, with, mCRPC]), verbo([suggests]), complemento([a, 'reproducible,', but, highly, complex, molecular, profile, that, includes, common, aberrations, in, 'AR,', 'ERG,', 'c-MET,', and, 'PI3K', signaling, during, mCRPC, 'progression,', which, may, be, useful, for, predictive, biomarker, development])]). relacion([sujeto(['Hyperosmolarity']), verbo([decreases]), complemento(['claudin-2', expression, in, renal, tubular, epithelial, 'cells,', but, the, molecular, mechanism, remains, undefined])]). relacion([sujeto(['Here,', we]), verbo([found]), complemento([that, the, 'hyperosmolarity-induced', decrease, in, 'claudin-2', expression, is, inhibited, by, 'Go6983,', a, 'non-selective', protein, kinase, 'C', '(', 'PKC)', 'inhibitor,', and, 'PKCβ', specific, inhibitor, in, 'Madin-Darby', canine, kidney, 'II', cells])]). relacion([sujeto(['Hyperosmolarity']), verbo([increased]), complemento([intracellular, free, 'Ca(2+)', concentration, and, phosphorylated, 'PKCβ', 'level,', which, were, inhibited, by, 'RN-1734,', an, antagonist, of, transient, receptor, potential, vanilloid, 4, channel])]). relacion([sujeto(['Phorbol', 12, -, myristate, 13, -, 'acetate,', a, 'PKC', 'activator,']), verbo([decreased]), complemento(['claudin-2', expression])]). relacion([sujeto(['These', results, indicate, hyperosmolarity]), verbo([decreases]), complemento(['claudin-2', expression, mediated, by, the, activation, of, 'RN-1734-sensitive', channel, and, 'PKCβ'])]). relacion([sujeto(['Hyperosmolarity']), verbo([decreased]), complemento([promoter, activity, of, 'claudin-2,', which, was, inhibited, by, 'Go6983', and, 'PKCβ', inhibitor, similar, to, those, in, 'real-time', 'PCR', and, 'Western', blotting])]). relacion([sujeto(['Claudin-2']), verbo([has]), complemento(['hyperosmolarity-sensitive', region, in, its, 'promoter,', which, includes, 'GATA', binding, site])]). relacion([sujeto(['Hyperosmolarity']), verbo([decreased]), complemento([the, nuclear, level, of, 'GATA-2,', which, was, inhibited, by, 'Go6983', and, 'PKCβ', inhibitor])]). relacion([sujeto(['Mutation', of, 'GATA']), verbo([binding]), complemento([site, decreased, the, basal, promoter, activity, and, inhibited, the, effect, of, hyperosmolarity])]). relacion([sujeto(['In', 'contrast,', the, 'hyperosmolarity-induced']), verbo([decrease]), complemento([in, reporter, activity, and, 'claudin-2', expression, were, rescued, by, 'over-expression', of, wild, type, 'GATA-2'])]). relacion([sujeto(['Chromatin', immunoprecipitation, assay, showed, that, 'GATA-2']), verbo([bound]), complemento([to, promoter, region, of, 'claudin-2'])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, hyperosmolarity, decreases, the, expression, level, of, 'claudin-2', via, a, decrease, in, 'PKCβ-dependent', 'GATA-2', transcriptional, activity, in, renal, tubular, epithelial, cells])]). relacion([sujeto(['The', extensive, network, of, signaling, molecules, and, transcription, factors]), verbo([required]), complemento([for, determination, and, terminal, differentiation, of, specific, cell, types, is, still, not, fully, understood])]). relacion([sujeto(['The', 'SRY-like', 'HMG-box', '(', 'SOX)', transcription, factor, 'Sox4', plays, important, roles, in, many, developmental, processes, and]), verbo([has]), complemento([two, homologs, in, 'zebrafish,', 'Sox4a', and, 'Sox4b'])]). relacion([sujeto(['We', show, that, the, sox4b, gene, is]), verbo([expressed]), complemento([in, the, pituitary, anlagen, starting, at, 24, h, after, fertilization, '(', 'hpf)', and, later, in, the, entire, head, region, including, the, pituitary])]). relacion([sujeto(['Loss', of, 'Sox4b', 'function,', using, morpholino, knockdown, or, expression, of, a, 'dominant-negative', 'Sox4', 'mutant,']), verbo([leads]), complemento([to, a, drastic, decrease, in, tshβ, and, gsuα, expression, and, reduced, levels, of, 'gh,', whereas, other, anterior, pituitary, gland, markers, including, 'prl,', 'slβ,', 'pomc,', and, lim3, are, not, affected])]). relacion([sujeto(['Sox4b', is, also]), verbo([required]), complemento([for, expression, of, gata2a, in, the, pituitary])]). relacion([sujeto(['Knockdown', of, gata2a]), verbo([leads]), complemento([to, decreased, tshβ, and, gsuα, expression, at, 48, 'hpf,', similar, to, sox4b, morphants])]). relacion([sujeto(['Finally,', sox4b, or, gata2a, knockdown]), verbo([causes]), complemento([a, significant, decrease, of, gonadotropin, expression, '(', lhβ, and, 'fshβ)', at, 4, d, after, fertilization])]). relacion([sujeto(['In', 'summary,', our, results, indicate, that, 'Sox4b', is]), verbo([expressed]), complemento([in, zebrafish, during, pituitary, development, and, plays, a, crucial, role, in, the, differentiation, of, thyrotrope, and, gonadotrope, cells, through, induction, of, gata2a, expression, in, the, developing, pituitary])]). relacion([sujeto(['Thyrotropin-releasing', hormone, '(', 'TRH)']), verbo([activates]), complemento([not, only, the, secretion, of, thyrotropin, '(', 'TSH)', but, also, the, transcription, of, 'TSHβ', and, 'α-glycoprotein', '(', 'αGSU)', subunit, genes])]). relacion([sujeto(['TSHβ', expression, is]), verbo([maintained]), complemento([by, two, transcription, 'factors,', 'Pit1', and, 'GATA2,', and, is, negatively, regulated, by, thyroid, hormone, '(', 'T3)'])]). relacion([sujeto(['Our', prior, studies]), verbo([suggest]), complemento([that, the, main, activator, of, the, 'TSHβ', gene, is, 'GATA2,', not, 'Pit1', or, unliganded, 'T3', receptor, '(', 'TR)'])]). relacion([sujeto(['In', previous, studies, on, the, mechanism, of, 'TRH-induced', activation, of, the, 'TSHβ', 'gene,', the, involvements, of, 'Pit1', and, 'TR']), verbo([have]), complemento([been, 'investigated,', but, the, role, of, 'GATA2', has, not, been, clarified])]). relacion([sujeto(['Using', 'kidney-derived', 'CV1', cells, and, 'pituitary-derived', 'GH3', and, 'TαT1', 'cells,', we, demonstrate, here, that, 'TRH', signaling]), verbo([enhances]), complemento(['GATA2-dependent', activation, of, the, 'TSHβ', promoter, and, that, 'TRH-induced', activity, is, abolished, by, amino, acid, substitution, in, the, 'GATA2-Zn', finger, domain, or, mutation, of, 'GATA-responsive', element, in, the, 'TSHβ', gene])]). relacion([sujeto(['In', 'CV1', cells, transfected, with, 'TRH', receptor, expression, 'plasmid,', 'GATA2-dependent', transactivation, of, αGSU, and, 'endothelin-1', promoters, was]), verbo([enhanced]), complemento([by, 'TRH'])]). relacion([sujeto(['While', inhibition, by, 'T3', is, dominant, over, 'TRH-induced', 'activation,', unliganded, 'TR', or, the, putative, negative, 'T3-responsive', element, are, not]), verbo([required]), complemento([for, 'TRH-induced', stimulation])]). relacion([sujeto(['Studies', using, 'GH3', cells, showed, that, 'TRH-induced', activity, of, the, 'TSHβ', promoter, depends, on, protein, kinase, 'C', but, not, the, 'mitogen-activated', protein, 'kinase,']), verbo([suggesting]), complemento([that, the, signaling, pathway, is, different, from, that, in, the, prolactin, gene])]). relacion([sujeto(['Much', is, known, about, how, genes]), verbo([regulated]), complemento([by, nuclear, receptors, '(', 'NRs)', are, switched, on, in, the, presence, of, a, ligand])]). relacion([sujeto(['More', 'recently,', 'cell-based', assays]), verbo([have]), complemento([shown, that, the, 'Zn-finger', region, of, 'GATA2', '(', 'GATA2-Zf)', has, an, important, role, in, 'down-regulation', of, the, thyrotropin, gene, '(', 'TSHβ)', by, liganded, thyroid, hormone, receptor, '(', 'TR)'])]). relacion([sujeto(['In', an, effort, to, better, understand, the, mechanism, that, drives, 'TSHβ', 'down-regulation', by, a, liganded, 'TR', and, 'GATA2,', we]), verbo([have]), complemento([carried, out, equilibrium, binding, assays, using, fluorescence, anisotropy, to, study, the, interaction, of, recombinant, 'TR', and, 'GATA2-Zf', with, regulatory, elements, present, in, the, 'TSHβ', promoter])]). relacion([sujeto(['Surprisingly,', we, observed, that, ligand, '(', 'T3)', weakens, 'TR']), verbo([binding]), complemento([to, a, negative, regulatory, element, '(', 'NRE)', present, in, the, 'TSHβ', promoter])]). relacion([sujeto(['We', also, show, that, 'TR', may]), verbo([interact]), complemento([with, 'GATA2-Zf', in, the, absence, of, 'ligand,', but, 'T3', is, crucial, for, increasing, the, affinity, of, this, complex, for, different, 'GATA', response, elements, '(', 'GATA-REs)'])]). relacion([sujeto(['Importantly,', these, results, indicate, that, 'TR', complex, formation]), verbo([enhances]), complemento(['DNA', binding, of, the, 'TR-GATA2', in, a, 'ligand-dependent', manner])]). relacion([sujeto(['Our', findings, extend, previous, results, obtained, in, 'vivo,', further, improving, our, understanding, of, how, liganded]), verbo([nuclear]), complemento([receptors, 'down-regulate', gene, 'transcription,', with, the, cooperative, binding, of, transcription, factors, to, 'DNA', forming, the, core, of, this, process])]). relacion([sujeto(['GATA2', 'Zn', finger, 'domain,', which, is, known, to]), verbo([recognize]), complemento(['GATA-responsive', elements, '(', 'GATA-REs),', is, essential, for, cooperation, by, 'PIT1'])]). relacion([sujeto(['Transactivation', of, 'TSHbeta', promoter]), verbo([requires]), complemento(['PIT1-binding', site, upstream, to, 'GATA-REs', '(', 'PIT1-US),', and, the, spacing, between, 'PIT1-US', and, 'GATA-REs', strictly, determines, the, cooperation, between, 'PIT1', and, 'GATA2'])]). relacion([sujeto(['The', deleted, region, '(', nt, -, 82, /, -, 52, ')', designated, as, a, suppressor, region, '(', 'SR)', was, considered, to]), verbo([inhibit]), complemento([transactivation, by, 'GATA2'])]). relacion([sujeto(['Electrophoretic', mobility, shift, assay]), verbo([suggested]), complemento([that, some, nuclear, factor, exists, in, 'CV1', 'cells,', which, binds, with, 'SR', and, this, interaction, was, blocked, by, recombinant, 'PIT1'])]). relacion([sujeto(['Transcriptional', repression, of, the, 'TSH-specific', beta, subunit, '(', 'TSHbeta)', gene]), verbo([has]), complemento([been, regarded, to, be, specific, to, thyroid, hormone, '(', 'tri-iodothyronine,', 'T(3))', and, its, receptors, '(', 'TRs)', in, physiological, conditions])]). relacion([sujeto(['However,', 'TSHbeta', mRNA, levels, in, the, pituitary, were]), verbo([reported]), complemento([to, decrease, in, the, administration, of, pharmacologic, doses, of, estrogen, '(', 17, -, 'beta-estradiol,', 'E(2))', and, increase, in, 'E(2)', receptor, '(', 'ER)-alpha', null, mice])]). relacion([sujeto(['In', 'kidney-derived', 'CV1', 'cells,', transcriptional, activity, of, the, 'TSHbeta', promoter, was]), verbo([stimulated]), complemento([by, 'GATA2', and, suppressed, by, 'THRBs', and, 'ERalpha', in, a, 'ligand-dependent', fashion])]). relacion([sujeto(['Overexpression', of, 'PIT1', diminished, the, 'E(2)-ERalpha-induced', 'inhibition,']), verbo([suggesting]), complemento([that, 'PIT1', may, protect, 'GATA2', from, 'E(2)-ERalpha', targeting, by, forming, a, stable, complex, with, 'GATA2'])]). relacion([sujeto(['E(2)-dependent', inhibition]), verbo([requires]), complemento([the, 'ERalpha', 'amino-terminal', domain, but, not, the, tertiary, structure, of, the, second, 'Zn', finger, motif, in, 'E(2)-ERalpha-DBD'])]). relacion([sujeto(['Previously', we]), verbo([reported]), complemento([that, the, negative, regulation, of, the, 'TSHbeta', gene, by, 'T(3)', and, its, receptor, '[', thyroid, hormone, receptor, '(', 'TR)]', is, observed, in, 'CV1', cells, when, 'GATA2', and, 'Pit1', are, introduced])]). relacion([sujeto(['The', negative, regulatory, element, '(', 'NRE),', which, had, been]), verbo([reported]), complemento([to, mediate, 'T(3)-bound', 'TR', '(', 'T(3)-TR)-dependent', 'inhibition,', is, 'dispensable,', because, deletion, or, mutation, of, 'NRE', did, not, impair, suppression])]). relacion([sujeto(['The', reporter, 'construct,', 'TSHbeta-D4-chloramphenicol', 'acetyltransferase,', which, possesses, only, the]), verbo([binding]), complemento([sites, for, 'Pit1', and, 'GATA2,', was, activated, by, 'GATA2', 'alone,', and, this, transactivation, was, specifically, inhibited, by, 'T(3)-TR'])]). relacion([sujeto(['The', 'Zn', finger, region, of, 'GATA2']), verbo([interacts]), complemento([with, the, 'DNA-binding', domain, of, 'TR', in, a, 'T(3)-independent', manner])]). relacion([sujeto(['Chromatin', immunoprecipitation, assays, with, a, thyrotroph, cell, 'line,', 'TalphaT1,', revealed, that, 'T(3)', treatment]), verbo([recruited]), complemento([histone, deacetylase, 3, ',', reduced, the, acetylation, of, histone, 'H4,', and, caused, the, dissociation, of, 'TRAP220', within, 15, -, 30, min])]). relacion([sujeto(['In', the, negative, regulation, of, the, 'TSHbeta', gene, by, 'T(3)-TR', we]), verbo([report]), complemento([that, 1, ')', 'GATA2', is, the, major, transcriptional, activator, of, the, 'TSHbeta', 'gene,', 2, ')', the, putative, 'NRE', previously, reported, is, not, 'required,', 3, ')', 'TR-DNA-binding', domain, directly, interacts, with, the, 'Zn', finger, region, of, 'GATA2,', and, 4, ')', histone, deacetylation, and, 'TRAP220', dissociation, are, important])]). relacion([sujeto(['Structure', prediction, analysis, revealed, that, most, of, the, 'GATA2', mutations, were, located, at, the, 'DNA-binding', 'N-terminal', 'zinc-finger', near, the, 'DNA-binding', 'interface,']), verbo([suggesting]), complemento([that, mutations, could, result, in, at, least, partial, inactivation, of, 'GATA2', protein])]). relacion([sujeto(['On', 'co-transfection', of, a, 'GATA-responsive', reporter, construct, together, with, plasmids]), verbo([expressing]), complemento([either, 'GATA2', 'wild-type', or, 'GATA2', 'ZF1', mutants, '(', 'P304H,', 'L321P', and, 'R330X)', in, 293, 'T', 'cells,', we, found, a, reduced, transcriptional, activation, in, cells, transfected, with, 'GATA2', mutants])]). relacion([sujeto(['To', determine, whether, reduced, 'GATA2', function, is]), verbo([involved]), complemento([in, leukemogenesis, of, 'AEL,', we, transfected, 32, 'D', cells, with, 'GATA2', mutants, and, evaluated, the, impact, of, 'GATA2', mutations, on, erythroid, differentiation])]). relacion([sujeto(['Our', data, revealed, an]), verbo([increased]), complemento([expression, of, 'erythroid-related', antigens, 'Ter-119,', 'β-globin', and, 'βh1-globin,', as, well, as, increased, hemoglobin, positivity, in, 32, 'D', cells, transfected, with, 'GATA2', mutants, compared, with, control, cells])]). relacion([sujeto(['Our', results]), verbo([suggest]), complemento([that, the, decline, of, 'GATA2', resulting, from, mutations, contributes, to, the, erythroid, 'commitment,', differentiation, and, the, development, of, 'AEL'])]). relacion([sujeto(['Mutation', in, 'GATA2', results, in, the]), verbo([loss]), complemento([of, function, or, even, gain, of, 'function,', including, abnormal, proliferation, of, white, blood, cells, that, may, predispose, to, acute, myeloid, leukemia])]). relacion([sujeto(['Our', results, showed, that, the, codon, usage, in, 'GATA2']), verbo([has]), complemento([been, influenced, by, 'GC', mutation, bias, where, nature, has, highly, favored, fourteen, most, over, represented, codons, but, disfavored, the, 'ATA', codon, across, five, mammals])]). relacion([sujeto(['Purifying', natural, selection]), verbo([has]), complemento([affected, 'GATA2', gene, in, human, and, other, mammals, to, maintain, its, protein, function, during, the, period, of, evolution])]). relacion([sujeto(['Our', findings]), verbo([report]), complemento([an, insight, into, the, codon, usage, patterns, in, gaining, the, clues, for, codon, optimization, to, alter, the, translational, efficiency, as, well, as, for, the, functional, conservation, of, gene, expression, and, the, significance, of, nucleotide, composition, in, 'GATA2', gene, within, mammals])]). relacion([sujeto(['In', vitro, studies]), verbo([suggest]), complemento([that, 'Gata2', modulates, adipocyte, differentiation, and, mesenchymal, stem, cell, '(', 'MSC)', proliferation])]). relacion([sujeto(['To', systematically, determine, the, in, vivo, functions, of, 'Gata2', in, the, 'MSC', lineage, commitment, and, 'development,', we]), verbo([have]), complemento([generated, three, mouse, models, in, which, 'Gata2', is, specifically, deleted, in, 'MSCs,', 'adipocytes,', or, osteoblasts])]). relacion([sujeto(['During', the, 'MSC', expansion, 'stage,', 'Gata2']), verbo([promotes]), complemento([proliferation, and, attenuates, 'differentiation;', thereby, 'Gata2', loss, in, 'MSCs', results, in, enhanced, differentiation, of, both, adipocytes, and, osteoblasts])]). relacion([sujeto(['During', the, differentiation, 'stage,', 'Gata2', also, plays, 'MSC-independent', roles, to, impede, lineage, 'commitment;', 'hence,', 'Gata2']), verbo([loss]), complemento([in, adipocyte, or, osteoblast, lineages, also, augments, adipogenesis, and, 'osteoblastogenesis,', respectively])]). relacion([sujeto(['These', findings]), verbo([reveal]), complemento(['Gata2', as, a, crucial, rheostat, of, 'MSC', fate, to, control, osteoblast, and, adipocyte, lineage, development])]). relacion([sujeto(['Heterozygous', mutations, in, the, transcriptional, regulator, 'GATA-2']), verbo([associate]), complemento([with, multilineage, 'immunodeficiency,', myelodysplastic, syndrome, '(', 'MDS),', and, acute, myeloid, leukemia, '(', 'AML)'])]). relacion([sujeto(['The', majority, of, these, mutations, localize, in, the, zinc, finger, '(', 'ZnF)', 'domains,', which]), verbo([mediate]), complemento(['GATA-2', 'DNA', binding])]). relacion([sujeto(['Upon', 'Gata2', 'C-ZnF', 'deletion,', we, observed, rapid, peripheral, 'cytopenia,', bone, marrow, 'failure,', and]), verbo([decreased]), complemento(['c-Kit', expression, on, hematopoietic, progenitors])]). relacion([sujeto(['Transplant', studies, indicated, 'GATA-2']), verbo([has]), complemento([a, 'cell-autonomous', role, in, bone, marrow, hematopoiesis])]). relacion([sujeto(['Moreover,', myeloid, lineage, populations, were, particularly, sensitive, to, 'Gata2', 'hemizygosity,', while, molecular, assays, indicated, 'GATA-2']), verbo([regulates]), complemento(['c-Kit', expression, in, multilineage, progenitor, cells])]). relacion([sujeto(['Enforced', 'c-Kit', expression, in, 'Gata2', 'C-ZnF-deficient', hematopoietic, progenitors]), verbo([enhanced]), complemento([myeloid, colony, 'activity,', suggesting, 'GATA-2', sustains, myelopoiesis, via, a, cell, intrinsic, role, involving, maintenance, of, 'c-Kit', expression])]). relacion([sujeto(['Our', results]), verbo([provide]), complemento([insight, into, mechanisms, regulating, hematopoiesis, in, bone, marrow, and, may, contribute, to, a, better, understanding, of, immunodeficiency, and, bone, marrow, failure, associated, with, 'GATA-2', mutation])]). relacion([sujeto(['Heterozygous', germline, mutations, in, the, zinc, finger, transcription, factor, 'GATA2']), verbo([have]), complemento([recently, been, shown, to, underlie, a, range, of, clinical, 'phenotypes,', including, 'Emberger', 'syndrome,', a, disorder, characterized, by, lymphedema, and, predisposition, to, myelodysplastic, 'syndrome/acute', myeloid, leukemia, '(', 'MDS/AML)'])]). relacion([sujeto(['Despite', 'well-defined', roles, in, 'hematopoiesis,', the, functions, of, 'GATA2', in, the, lymphatic, vasculature, and, the, mechanisms, by, which, 'GATA2', mutations, result, in, lymphedema]), verbo([have]), complemento([not, been, characterized])]). relacion([sujeto(['Here,', we]), verbo([have]), complemento([provided, a, molecular, explanation, for, lymphedema, predisposition, in, a, subset, of, patients, with, germline, 'GATA2', mutations])]). relacion([sujeto(['Specifically,', we, demonstrated, that, 'Emberger-associated', 'GATA2', missense, mutations, result, in, complete]), verbo([loss]), complemento([of, 'GATA2', 'function,', with, respect, to, the, capacity, to, regulate, the, transcription, of, genes, that, are, important, for, lymphatic, vessel, valve, development])]). relacion([sujeto(['We', identified, a, putative, enhancer, element, upstream, of, the, key, lymphatic, transcriptional, regulator, 'PROX1', that, is]), verbo([bound]), complemento([by, 'GATA2,', and, the, transcription, factors, 'FOXC2', and, 'NFATC1'])]). relacion([sujeto(['Emberger', 'GATA2', missense, mutants, had, a, profoundly, reduced, capacity, to]), verbo([bind]), complemento([this, element])]). relacion([sujeto(['Conditional', 'Gata2', deletion, in, mice, revealed, that, 'GATA2', is]), verbo([required]), complemento([for, both, development, and, maintenance, of, lymphovenous, and, lymphatic, vessel, valves])]). relacion([sujeto(['The', transcriptional, regulation, of, the, gene, encoding, 'α-synuclein', '(', 'SNCA)', is, thought, to, play, a, critical, role, in, the, pathogenesis, of, 'Parkinson\'s', disease, '(', 'PD),', as, common, genetic, variability, in, this, gene, is]), verbo([associated]), complemento([with, an, elevated, risk, of, developing, 'PD'])]). relacion([sujeto(['So', 'far,', only, few, proteins]), verbo([have]), complemento([been, identified, as, transcription, factors, '(', 'TFs)', of, 'SNCA', in, cellular, models])]). relacion([sujeto(['Here', we, show, that, two, of, these, 'TFs']), verbo([bind]), complemento([to, the, 'DNA', in, human, brain, 'tissue:', the, zinc, finger, protein, 'ZSCAN21', occupies, a, region, within, 'SNCA', intron, 1, ',', as, described, 'before,', while, 'GATA2', occupies, a, specific, region, within, intron, 2, ',', where, we, have, identified, a, new, binding, site, within, the, complex, structure, of, the, 5, '\'', -, promoter, region, of, 'SNCA'])]). relacion([sujeto(['Electrophoretic', mobility, shift, assays, confirmed, these]), verbo([binding]), complemento([sites])]). relacion([sujeto(['Heterozygous', familial, or, sporadic, 'GATA2', mutations]), verbo([cause]), complemento([a, multifaceted, 'disorder,', encompassing, susceptibility, to, 'infection,', pulmonary, 'dysfunction,', 'autoimmunity,', lymphoedema, and, malignancy])]). relacion([sujeto(['Although', often, healthy, in, 'childhood,', carriers, of, defective, 'GATA2', alleles, develop, progressive]), verbo([loss]), complemento([of, mononuclear, cells, '(', dendritic, 'cells,', 'monocytes,', 'B', and, 'Natural', 'Killer', 'lymphocytes),', elevated, 'FLT3', 'ligand,', and, a, 90, '%', risk, of, clinical, 'complications,', including, progression, to, myelodysplastic, syndrome, '(', 'MDS)', by, 60, years, of, age])]). relacion([sujeto(['Mutations', appear, to]), verbo([cause]), complemento(['haplo-insufficiency,', which, is, known, to, impair, haematopoietic, stem, cell, survival, in, animal, models])]). relacion([sujeto(['Our', goal, was, to, identify, any, differences, in, microRNA, '(', 'miRNA)', expression, profiles, of, gingival, tissue, in, periodontitis, when, obesity, is, 'present,', which, may]), verbo([suggest]), complemento([novel, molecular, pathways, that, this, miRNA, network, may, affect])]). relacion([sujeto(['In', silico, identification, of, previously, confirmed, miRNA, gene]), verbo([targets]), complemento([was, conducted, through, miRTarBase, and, miRWalk, 'databases,', and, pathway, enrichment, analysis, identified, enriched, miRNA, gene, sets])]). relacion([sujeto(['The', gingival, tissue, miRNA, profile, of, obese, 'patients,', compared, to, that, of, normal, weight, 'patients,', showed, 13, upregulated, and, 22, downregulated, 'miRNAs,', among, which, 'miR-200b', was, validated, by, 'qRT-PCR', to, be, significantly]), verbo([increased]), complemento([in, obesity])]). relacion([sujeto(['Functional', analysis, of, 51, experimentally, validated, 'miR-200b', gene]), verbo([targets]), complemento([identified, enrichment, of, genes, involved, in, cell, 'motility,', 'differentiation,', 'DNA', 'binding,', response, to, 'stimulus,', and, vasculature, development, pathways, not, previously, identified, in, the, 'obesity-specific', disease, profile])]). relacion([sujeto(['Furthermore,', the, expression, of, the, 'miR-200b', gene]), verbo([targets]), complemento(['ZEB1/2,', 'GATA2,', and, 'KDR', was, confirmed, by, 'qRT-PCR', as, being, lower, in, obese, patients, with, periodontitis, versus, normal, weight, 'patients,', suggesting, a, role, of, 'miR-200b', in, regulation, of, a, set, of, gene, targets, and, biological, pathways, relevant, to, wound, healing, and, angiogenesis])]). relacion([sujeto(['Functional', studies, to, explore, the, role, of, 'miR-200b', in, the, above, processes, may, offer, new, insights, on, putative, therapeutic]), verbo([targets]), complemento([for, this, group, of, patients])]). relacion([sujeto(['The', 'CXXC5', gene, encodes, a, transcriptional, activator, with, a, 'zinc-finger', 'domain,', and, high, expression, in, human, acute, myeloid, leukemia, '(', 'AML)', cells, is]), verbo([associated]), complemento([with, adverse, prognosis])]). relacion([sujeto(['High', 'CXXC5', expression, was, also]), verbo([associated]), complemento([with, high, mRNA, expression, of, several, stem, 'cell-associated', transcriptional, 'regulators,', the, strongest, associations, being, with, 'WT1,', 'GATA2,', 'RUNX1,', 'LYL1,', 'DNMT3,', 'SPI1,', and, 'MYB'])]). relacion([sujeto(['Finally,', 'CXXC5', knockdown, in, human, 'AML', cell, lines]), verbo([caused]), complemento([significantly, increased, expression, of, the, potential, tumor, suppressor, gene, 'TSC22', and, genes, encoding, the, growth, factor, receptor, 'KIT,', the, cytokine, 'Angiopoietin', 1, and, the, 'selenium-containing', glycoprotein, 'Selenoprotein', 'P'])]). relacion([sujeto(['GATA2', deficiency, is, a, germline, disease, that]), verbo([causes]), complemento([a, wide, spectrum, of, phenotypes, including, viral, and, bacterial, 'infections,', 'cytopenias,', 'myelodysplasia,', myeloid, 'leukemias,', pulmonary, alveolar, proteinosis, and, lymphedema])]). relacion([sujeto(['GATA2', mutations]), verbo([have]), complemento([been, found, in, up, to, 10, '%', of, those, with, congenital, neutropenia, 'and/or', aplastic, anemia])]). relacion([sujeto(['Heterozygous', mutations, appear, to]), verbo([cause]), complemento([haploinsufficiency, due, to, either, protein, dysfunction, or, uniallelic, reduced, transcription])]). relacion([sujeto(['Bone', marrow, transplantation]), verbo([has]), complemento([been, successful, for, both, hematopoietic, and, pulmonary, alveolar, proteinosis, repair])]). relacion([sujeto(['GATA2', deficiency, is]), verbo([caused]), complemento([by, a, variety, of, mutations, in, the, 'GATA2', gene, and, can, have, variable, 'presentation,', onset, and, outcome])]). relacion([sujeto(['Recently,', mutations, of, the, 'GATA']), verbo([binding]), complemento([protein, 2, '(', 'GATA2)', gene, were, identified, in, acute, myeloid, leukemia, '(', 'AML)', patients, with, 'CEBPA', double, mutations, '(', 'CEBPA', '(', 'double-mut)),', but, the, interaction, of, this, mutation, with, other, genetic, alterations, and, its, dynamic, changes, during, disease, progression, remain, to, be, determined])]). relacion([sujeto(['In', this, 'study,', 14, different, missense, 'GATA2', 'mutations,', which, were, all, clustered, in, the, highly]), verbo([conserved]), complemento(['N-terminal', zinc, finger, 1, 'domain,', were, identified, in, 27.4, ',', 6.7, ',', and, 1, &, 'nbsp;%', of, patients, with, 'CEBPA', '(', 'double-mut),', 'CEBPA', '(', 'single-mut),', and, 'CEBPA', wild, 'type,', respectively])]). relacion([sujeto(['GATA2', mutations, were, closely]), verbo([associated]), complemento([with, younger, 'age,', 'FAB', 'M1', 'subtype,', 'intermediate-risk', 'cytogenetics,', expression, of, 'HLA-DR,', 'CD7,', 'CD15,', or, 'CD34', on, leukemic, 'cells,', and, 'CEBPA', 'mutation,', but, negatively, associated, with, 'FAB', 'M4', 'subtype,', 'favorable-risk', 'cytogenetics,', and, 'NPM1', mutation])]). relacion([sujeto(['She']), verbo([has]), complemento([history, of, thrombocytopenia, for, 25, &, 'nbsp;years', and, a, significant, family, history, of, 'thrombocytopenia,', affecting, her, 'mother,', siblings, and, their, 'children,', as, well, as, her, own, children])]). relacion([sujeto(['Given', the, 'patient\'s', family, history, and, clinical, 'manifestation,', this, was, interpreted, as, an, acute, myeloid, leukemia, with, heritable, 'GATA2', mutations]), verbo([associated]), complemento([with, familial, 'AML-MDS'])]). relacion([sujeto(['Germline', 'GATA2', mutations, are]), verbo([involved]), complemento([in, a, group, of, complex, syndromes, with, overlapping, clinical, features, of, immune, 'deficiency,', lymphedema, and, propensity, to, acute, myeloid, leukemia, or, myelodysplastic, syndrome, '(', 'AML-MDS)'])]). relacion([sujeto(['Here', we]), verbo([reported]), complemento([a, case, of, familial, 'AML-MDS', with, two, novel, 'GATA2', mutations])]). relacion([sujeto(['This', case, illustrates, the, importance, of]), verbo([recognizing]), complemento([the, clinical, features, for, this, rare, category, of, 'AML-MDS', and, performing, the, appropriate, molecular, testing])]). relacion([sujeto(['The', diagnosis, of, heritable, gene, mutations]), verbo([associated]), complemento([familial, 'AML-MDS', has, significant, clinical, implication, for, the, patients, and, affected, families])]). relacion([sujeto(['The', 'GATA2', gene, encodes, a, 'zinc-finger', transcription, factor, that]), verbo([acts]), complemento([as, a, master, regulator, of, normal, hematopoiesis])]). relacion([sujeto(['Mutations', in, 'GATA2']), verbo([have]), complemento([been, implicated, in, the, development, of, myelodysplastic, syndrome, and, acute, myeloid, leukemia, '(', 'AML)'])]). relacion([sujeto(['Using', 'RNA', sequencing, we, now]), verbo([report]), complemento([that, 'GATA2', is, either, mutated, with, a, functional, 'consequence,', or, expressed, at, low, levels, in, the, majority, of, normal, karyotype, 'AML', '(', 'NK-AML)'])]). relacion([sujeto(['From', a, broader, 'perspective,', this, work]), verbo([suggests]), complemento([for, the, first, time, that, determinants, of, 'ASE', likely, have, a, key, role, in, human, leukemia])]). relacion([sujeto(['Here', we]), verbo([found]), complemento([that, 'GATA-2', negatively, regulated, 'TGF-β', signaling, pathway, in, 'Smad4-dependent', manner])]). relacion([sujeto(['GATA-2', specifically]), verbo([interacts]), complemento([with, 'Smad4', with, its, 'N-terminal', while, the, zinc, finger, domain, of, 'GATA-2', is, essential, for, negative, regulation, of, 'TGFβ'])]). relacion([sujeto(['Although', 'GATA-2', did, not, affect, the, phosphorylation, of, 'Smad2/3', and, the, complex, 'Smad2/3/4', formation, in, response, to, 'TGFβ,', the, 'DNA']), verbo([binding]), complemento([activity, of, 'Smad4', was, decreased, significantly, by, 'GATA-2', overexpression])]). relacion([sujeto(['Overexpression', of, 'GATA-2', in, 'K562', cells]), verbo([led]), complemento([to, reduced, 'TGFβ-induced', erythroid, differentiation, while, knockdown, of, 'GATA-2', enhanced, 'TGFβ-induced', erythroid, differentiation])]). relacion([sujeto(['All', these, results]), verbo([suggest]), complemento([that, 'GATA-2', is, a, novel, negative, regulator, of, 'TGFβ', signal, pathway])]). relacion([sujeto(['A350_N351ins8-GATA2', did, not, show, a, 'dominant-negative', effect, over, 'wild-type', '(', 'Wt)-GATA2', by, the, reporter, 'assay,', it, might, be]), verbo([involved]), complemento([in, the, pathophysiology, of, 'AML', by, impairing, myeloid, differentiation, because, of, little, 'Wt-GATA2', expression, in, primary, 'AML', cells, harboring, the, p])]). relacion([sujeto(['Since', 2010, ',', the, year, the, 'Patient', 'Protection', and, 'Affordable', 'Care', 'Act', '(', 'ACA)', became, 'law,', the, roundtable]), verbo([has]), complemento([convened, two, workshops, related, to, this, topic, as, well, as, commissioned, two, 'papers,', and, several, members, have, prepared, individually, written, perspectives])]). relacion([sujeto(['The', 'roundtable\'s', attention, to, the, topic, of, health, insurance, is, appropriate, because, health, reform]), verbo([has]), complemento([created, major, changes, in, the, health, care, system, in, this, country])]). relacion([sujeto(['It']), verbo([has]), complemento([brought, millions, of, people, into, the, system, that, previously, did, not, have, access])]). relacion([sujeto(['In', 'addition,', many, of, these, individuals]), verbo([have]), complemento([limited, experience, with, health, care, and, health, insurance, and, are, from, populations, that, traditionally, have, high, rates, of, low, health, literacy])]). relacion([sujeto(['Once', immunological, tests, are]), verbo([suggesting]), complemento([a, latent, tuberculosis, infection, it, should, be, considered, that, pregnant, women, have, an, increased, risk, of, developing, active, tuberculosis, with, potential, health, threats, for, the, unborn, child])]). relacion([sujeto(['Further', examinations, '(', such, as, 'ultrasound)', to, rule, out, extrapulmonary, 'TB', should, be, 'undertaken,', once, active, pulmonary, 'TB']), verbo([has]), complemento([been, ruled, out])]). relacion([sujeto(['A', treatment, indication, is, given, for, pregnant, women, during, 'pregnancy,', once, active, 'TB']), verbo([has]), complemento([been, veryfied])]). relacion([sujeto(['Up', to, 'now,', just, 'gain-of-function', mutations, of, 'KISS1/KISS1R', and, 'loss-of-function', mutations, of, the, maternally, imprinted, gene, 'MKRN3', are, the, known, genetic]), verbo([causes]), complemento([of, 'ICPP'])]). relacion([sujeto(['Our', intention, is, to, evaluate, variants, present, in, genes, related, to, the, pubertal, onset, pathway, that, could]), verbo([act]), complemento([as, 'disease-causing', or, predisposing, variants])]). relacion([sujeto(['In', a, &, 'quot;sporadic', 'case,"', we]), verbo([found]), complemento([a, missense, variant, in, 'MKRN3', 'NM_005664'])]). relacion([sujeto([203, 'G>A,']), verbo([causing]), complemento([the, protein, change, 'NP_005655'])]). relacion([sujeto(['We', did, not]), verbo([find]), complemento([any, pathogenic, variants, in, 'KISS1,', 'KISS1R,', 'LIN28,', 'GNRH,', 'GNRHR,', 'TACR3,', and, 'TAC3'])]). relacion([sujeto(['MKRN3', is, the, most, frequent, genetic]), verbo([cause]), complemento([of, familial, 'ICPP,', so, it, is, wise, to, screen, for, 'MKRN3', mutations, in, all, patients, with, familial, 'ICPP', and, in, patients, with, an, unclear, paternal, pubertal, history])]). relacion([sujeto(['Because', cannabis, use, is, a, major, public, health, concern, and, cannabis, is, known, to]), verbo([act]), complemento([on, central, 'neurotransmission,', studying, the, retinal, ganglion, cells, in, individuals, who, regularly, use, cannabis, is, of, interest])]). relacion([sujeto(['To', determine, whether, the]), verbo([regular]), complemento([use, of, cannabis, could, alter, the, function, of, retinal, ganglion, cells, in, humans])]). relacion([sujeto(['Twenty-eight', of, the, 52, participants, were]), verbo([regular]), complemento([cannabis, users, '(', 24, men, and, 4, 'women;', median, 'age,', 22, years, '[', 95, '%', 'CI,', 21, -, 24, 'years]),', and, the, remaining, 24, were, controls, '(', 20, men, and, 4, 'women;', median, 'age,', 24, years, '[', 95, '%', 'CI,', 23, -, 27, 'years])'])]). relacion([sujeto(['After', adjustment, for, the, number, of, years, of, education, and, alcohol, 'use,', there, was, a, significant]), verbo([increase]), complemento([for, cannabis, users, of, the, 'N95', implicit, time, on, results, of, pattern, electroretinography, '(', 'median,', 98.6, milliseconds, '[', 95, '%', 'CI,', 93.4, -, 99.5, ']', ')', compared, with, controls, '(', 'median,', 88.4, milliseconds, '[', 95, '%', 'CI,', 85.0, -, 91.1, ']', ')', ',', with, 8.4, milliseconds, as, the, median, of, the, differences, '(', 95, '%', 'CI,', 4.9, -, 11.5, ;, 'P', &, 'lt;'])]). relacion([sujeto(['Our', results, demonstrate, a, delay, in, transmission, of, action, potentials, by, the, ganglion, cells, in]), verbo([regular]), complemento([cannabis, 'users,', which, could, support, alterations, in, vision])]). relacion([sujeto(['Electronic', cigarette, '(', 'e-cigarette)', simulates, the]), verbo([act]), complemento([of, tobacco, smoking, by, vaporizing, a, mixture, of, propylene, 'glycol,', 'nicotine,', and, flavoring, agents])]). relacion([sujeto(['e-cigarette']), verbo([has]), complemento([been, proposed, as, a, product, able, to, aid, to, stop, smoking])]). relacion([sujeto(['The', aim, of, the, study, is, to, verify, the, clinical, variations, of, periodontal, health]), verbo([induced]), complemento([by, 'e-cigarettes', use, 'and,', 'moreover,', to, investigate, about, the, awareness, of, the, 'e-smokers', about, their, health, variations, and, about, their, hypothetical, need, to, turn, back, to, smoke, combustible, cigarettes])]). relacion([sujeto(['This', clinical, observational, pilot, study]), verbo([involved]), complemento([110, out, of, 350, 'smokers,', who, switched, to, 'e-cigarette'])]). relacion([sujeto(['A', questionnaire, to, 'self-assess', the, variations, of, some, parameters, of, general, 'health,', and, to, 'self-assess', the, need, to, smoke, combustible, 'cigarettes,', was, distributed, to, such, subjects]), verbo([involved]), complemento([in, the, study])]). relacion([sujeto(['Finally,', many, patients]), verbo([reported]), complemento([an, interesting, reduction, in, the, need, to, smoke])]). relacion([sujeto(['Dendritic', cells, '(', 'DCs)', and, monocytes, develop, from, a, series, of, 'bone-marrow-resident', progenitors, in, which, lineage, potential, is]), verbo([regulated]), complemento([by, distinct, transcription, factors])]). relacion([sujeto(['Zeb2', is, an, 'E-box-binding', protein]), verbo([associated]), complemento([with, 'epithelial-mesenchymal', transition, and, is, widely, expressed, among, hematopoietic, lineages])]). relacion([sujeto(['Previously,', we, observed, that, 'Zeb2', expression, is, differentially]), verbo([regulated]), complemento([in, progenitors, committed, to, classical, 'DC', '(', 'cDC)', subsets, in, vivo])]). relacion([sujeto(['In', 'addition,', we, confirm, a, requirement, for, 'Zeb2', in, development, of, plasmacytoid, 'DCs', but]), verbo([find]), complemento([that, 'Zeb2', is, not, required, for, cDC2, development])]). relacion([sujeto(['Instead,', 'Zeb2', may]), verbo([act]), complemento([to, repress, cDC1, progenitor, specification, in, the, context, of, inflammatory, signals])]). relacion([sujeto(['Rapid', 'Alkalinization', 'Factor', 1, '(', 'RALF1),', a, 'plant-derived', small, regulatory, 'peptide,']), verbo([inhibits]), complemento([cell, elongation, through, suppression, of, rhizosphere, acidification, in, plants])]). relacion([sujeto(['Although', a, 'receptor-like', 'kinase,', 'FERONIA', '(', 'FER),']), verbo([has]), complemento([been, shown, to, act, as, a, receptor, for, 'RALF1,', the, signaling, mechanism, remains, unknown])]). relacion([sujeto(['In', this, 'study,', we, identified, a, 'receptor-like', cytoplasmic, kinase, '(', 'RPM1-induced', protein, 'kinase,', 'RIPK),', a, plasma, 'membrane-associated', member, of, the, 'RLCK-VII', 'subfamily,', that, is]), verbo([recruited]), complemento([to, the, receptor, complex, through, interacting, with, 'FER', in, response, to, 'RALF1'])]). relacion([sujeto(['RALF1']), verbo([triggers]), complemento([the, phosphorylation, of, both, 'FER', and, 'RIPK', in, a, mutually, dependent, manner])]). relacion([sujeto(['Genetic', analysis, of, the, 'fer-4', and, ripk, mutants]), verbo([reveals]), complemento(['RIPK,', as, well, as, 'FER,', to, be, required, for, 'RALF1', response, in, roots])]). relacion([sujeto(['Our', results, demonstrate, that, '(', 'i)', active, mariner, elements, are, highly, invasive, and, characterized, by, an, elevated, transposition, 'rate,', confirming, their, capacity, to, spread, in, 'populations,', as, predicted, by, the, &, 'quot;selfish-DNA"', 'mechanism;', '(', 'ii)', nonautonomous, copies]), verbo([act]), complemento([as, parasites, of, autonomous, mariner, elements, by, hijacking, the, transposition, machinery, produced, by, active, 'mariner,', which, can, be, considered, as, a, case, of, 'hyperparasitism;', '(', 'iii)', this, behavior, resulted, in, a, failure, of, active, copies, to, amplify, which, systematically, drove, the, whole, family, to, extinction, in, less, than, 100, generations])]). relacion([sujeto(['The', protein, p63]), verbo([has]), complemento([been, identified, as, a, homolog, of, the, tumor, suppressor, protein, p53, and, is, capable, of, inducing, 'apoptosis,', cell, cycle, 'arrest,', or, senescence])]). relacion([sujeto([p63]), verbo([has]), complemento([at, least, six, 'isoforms,', which, can, be, divided, into, two, major, 'groups:', the, 'TAp63', variants, that, contain, the, 'N-terminal', transactivation, domain, and, the, 'ΔNp63', variants, that, lack, the, 'N-terminal', transactivation, domain])]). relacion([sujeto(['The', 'TAp63', variants, are, generally, considered, to, be, tumor, suppressors]), verbo([involved]), complemento([in, activating, apoptosis, and, suppressing, metastasis])]). relacion([sujeto(['ΔNp63', variants, cannot]), verbo([induce]), complemento([apoptosis, but, can, act, as, dominant, negative, inhibitors, to, block, the, function, of, 'TAp53,', 'TAp73,', and, 'TAp63'])]). relacion([sujeto([p63, is, rarely, mutated, in, human, tumors, and, is, predominately]), verbo([regulated]), complemento([at, the, 'post-translational', level, by, phosphorylation, and, ubiquitination])]). relacion([sujeto(['Here', we, show, that, splenic, 'or,', 'unexpectedly,', 'blood-borne', 'MDSC']), verbo([execute]), complemento(['far-reaching', immune, suppression, by, reducing, expression, of, the, 'L-selectin', lymph, node, '(', 'LN)', homing, receptor, on, naïve, 'T', and, 'B', cells])]). relacion([sujeto(['MDSC-induced', 'L-selectin']), verbo([loss]), complemento([occurs, through, a, 'contact-dependent,', 'post-transcriptional', mechanism, that, is, independent, of, the, major, 'L-selectin', 'sheddase,', 'ADAM17,', but, results, in, significant, elevation, of, circulating, 'L-selectin', in, 'tumor-bearing', mice])]). relacion([sujeto(['Furthermore,', 'T', cells, preconditioned, by, 'MDSC']), verbo([have]), complemento([diminished, responses, to, subsequent, antigen, 'exposure,', which, in, conjunction, with, reduced, 'trafficking,', severely, diminishes, 'antigen-driven', expansion, in, 'widely-dispersed', 'LN'])]). relacion([sujeto(['These', results, establish, novel, mechanisms, for, 'MDSC-mediated', immunosuppression, that]), verbo([have]), complemento([unanticipated, implications, for, systemic, cancer, immunity])]). relacion([sujeto(['This', study, aims, '(', 'a)', to, evaluate, the, prevalence, of, 'PTG', in, 'PICU', 'staff,', and, whether, their, scores, are, different, from, those]), verbo([reported]), complemento([by, professionals, working, in, other, pediatric, 'units,', '(', 'b)', to, explore, the, role, of, resilience, and, coping, strategies, in, predicting, 'PTG,', and, '(', 'c)', to, explore, the, relation, of, demographic, and, 'work-related', variables, with, 'PTG'])]). relacion([sujeto(['They', completed, the, 'Brief', 'Resilience', 'Scale,', a, 'Coping', 'Strategies', 'Questionnaire,', the, 'Posttraumatic', 'Growth', 'Inventory', '(', 'PTGI),', and]), verbo([provided]), complemento([demographic, and, 'work-related', information])]). relacion([sujeto(['Higher', 'PTG', was]), verbo([reported]), complemento([following, the, death, of, a, child, or, after, a, recent, conflict, with, a, work, colleague])]). relacion([sujeto(['Work-related', trauma, can]), verbo([act]), complemento([as, a, catalyst, for, positive, posttrauma, changes])]). relacion([sujeto(['Under', polluted, 'conditions,', rain, formation, is]), verbo([suppressed]), complemento([and, the, 'non-precipitating', clouds, act, to, warm, the, lower, part, of, the, cloudy, layer, '(', where, there, is, net, 'condensation)', and, cool, and, moisten, the, upper, part, of, the, cloudy, layer, '(', where, there, is, net, 'evaporation),', thereby, destabilizing, the, layer])]). relacion([sujeto(['Under', clean, 'conditions,', precipitation]), verbo([causes]), complemento([net, warming, of, the, cloudy, layer, and, net, cooling, of, the, 'sub-cloud', layer, '(', driven, by, rain, 'evaporation),', which, together, act, to, stabilize, the, atmosphere, with, time])]). relacion([sujeto(['Previous', studies]), verbo([have]), complemento([examined, different, aspects, of, the, effects, of, clouds, on, their, environment])]). relacion([sujeto(['Many', cohort, studies]), verbo([have]), complemento([shown, that, consumption, of, diets, containing, a, higher, composition, of, foods, derived, from, plants, reduces, mortality, from, coronary, heart, disease, '(', 'CHD)'])]). relacion([sujeto(['In', a, 'short-term', myocardial, infarction, '(', 'MI)', 'model,', intake, of, wheat, extract, '(', 'WE),', the, representative, cardioprotectant, identified, by, screening, approximately, 4, ',', 0, 'samples,', reduced, myocardial, injury, by]), verbo([inhibiting]), complemento(['apoptosis,', enhancing, 'ATP', 'production,', and, maintaining, protein, homeostasis])]). relacion([sujeto(['Finally,', the, food, components, of, 'plant-based', diets, that, contained, cell, wall, polysaccharides, rich, in, 'arabinose,', 'xylose,', and, possibly, fucose, were]), verbo([found]), complemento([to, confer, protection, against, myocardial, injury])]). relacion([sujeto(['These', results, show, for, the, first, time, that, specific, monosaccharides]), verbo([found]), complemento([in, the, cell, wall, polysaccharides, in, 'plant-based', diets, can, act, as, active, ingredients, that, reduce, 'CHD', by, inhibiting, postocclusion, 'steps,', including, 'MI', and, heart, failure])]). relacion([sujeto(['The', 'NET', '(', for, 'NocA,', 'Nlz,', 'Elbow,', 'TLP-1)', protein, family, is, a, group, of]), verbo([conserved]), complemento([zinc, finger, proteins, linked, to, embryonic, development, and, recently, associated, with, breast, cancer])]). relacion([sujeto(['The', members, of, this, family]), verbo([act]), complemento([as, transcriptional, repressors, interacting, with, both, class, 'I', histone, deacetylases, and, 'Groucho/TLE', 'co-repressors'])]). relacion([sujeto(['Here,', we, show, that, 'NET', family, members, are, present, and]), verbo([expressed]), complemento([in, multiple, metazoan, 'lineages,', from, cnidarians, to, vertebrates])]). relacion([sujeto(['We', identified, several, protein, domains]), verbo([conserved]), complemento([in, all, metazoan, species, or, in, specific, taxonomic, groups])]). relacion([sujeto(['Our', phylogenetic, analysis]), verbo([suggests]), complemento([that, the, 'NET', family, emerged, in, the, last, common, ancestor, of, cnidarians, and, bilaterians, and, that, several, rounds, of, independent, events, of, gene, duplication, occurred, throughout, evolution])]). relacion([sujeto(['Overall,', we]), verbo([provide]), complemento([novel, data, on, the, expression, and, evolutionary, history, of, the, 'NET', family, that, can, be, relevant, to, understanding, its, biological, role, in, both, normal, conditions, and, disease])]). relacion([sujeto(['In', 'sarcoidosis,', the, proinflammatory, cytokines, interferon, 'gamma,', tumour, necrosis, factor, and, 'interleukin-6', are]), verbo([released]), complemento([by, 'monocyte-derived', macrophages, and, lymphocytes, in, the, lungs, and, other, affected, tissues])]). relacion([sujeto(['Regulatory', receptors]), verbo([expressed]), complemento([on, monocytes, and, macrophages, act, to, suppress, cytokine, 'production,', and, reduced, expression, of, regulatory, receptors, may, thus, promote, tissue, inflammation])]). relacion([sujeto(['Cytokine']), verbo([release]), complemento([in, response, to, stimulation, of, whole, blood, was, measured, in, healthy, controls, and, 'Caucasian', 'non-smoking', patients, with, sarcoidosis, who, were, not, taking, disease, modifying, therapy])]). relacion([sujeto(['In', functional, 'studies,', blocking, the, 'CD200', axis]), verbo([increased]), complemento([production, of, 'TNF', and, 'IL-6'])]). relacion([sujeto(['Axonal', injury, is, a, common, feature, of, central, nervous, system, insults, that, culminates, with, the, death, of, the, affected, 'neurons,', and, an, irreversible]), verbo([loss]), complemento([of, function])]). relacion([sujeto(['Inflammation', is, an, important, component, of, the, neurodegenerative, 'process,', where, the, microglia, plays, an, important, role, by]), verbo([releasing]), complemento([proinflammatory, factors, as, well, as, clearing, the, death, neurons, by, phagocytosis])]). relacion([sujeto(['Here', we]), verbo([have]), complemento([identified, the, purinergic, signaling, through, the, 'P2X7', receptor, as, an, important, component, for, the, neuronal, death, in, a, model, of, optic, nerve, axotomy])]). relacion([sujeto(['We']), verbo([have]), complemento([found, that, in, 'P2X7', receptor, deficient, mice, there, is, a, delayed, loss, of, retinal, ganglion, cells, and, a, decrease, of, phagocytic, microglia, at, early, times, points, after, axotomy])]). relacion([sujeto(['In', contralateral, to, the, axotomy, 'retinas,', 'P2X7', receptor, controlled, the, numbers, of, phagocytic, 'microglia,']), verbo([suggesting]), complemento([that, extracellular, 'ATP', could, act, as, a, danger, signal, activating, the, 'P2X7', receptor, in, mediating, the, loss, of, neurons, in, contralateral, retinas])]). relacion([sujeto(['Thus,', our, work, demonstrates, that, 'P2X7', receptor, signaling, is]), verbo([involved]), complemento([in, neuronal, cell, death, after, axonal, 'injury,', being, 'P2X7', receptor, antagonism, a, potential, therapeutic, strategy])]). relacion([sujeto(['There', is]), verbo([increasing]), complemento([theoretical, interest, in, this, 'distinction,', but, little, is, known, about, perceived, emotion, genuineness, for, existing, facial, expression, databases])]). relacion([sujeto(['We', present, a, new, method, for, rating, perceived, genuineness, using, a, 'neutral-midpoint', scale, '(', -, 7, =, completely, 'fake;', 0, =, 'don\'t', 'know;', +, 7, =, completely, 'genuine)', 'that,', unlike, previous, 'methods,']), verbo([provides]), complemento([data, on, both, relative, and, absolute, perceptions])]). relacion([sujeto(['Normative', ratings, from, typically, developing, adults, for, five, emotions, '(', 'anger,', 'disgust,', 'fear,', 'sadness,', and, 'happiness)']), verbo([provide]), complemento([three, key, contributions])]). relacion([sujeto(['Second,', we]), verbo([provide]), complemento(['genuine/fake', norms, for, 558, faces, from, several, sources, '(', 'PoFA,', 'RaFD,', 'KDEF,', 'Gur,', 'FacePlace,', 'McLellan,', 'News', 'media),', including, a, list, of, 143, stimuli, that, are, 'event-elicited', '(', rather, than, 'posed)', 'and,', 'congruently,', perceived, as, reflecting, genuine, emotion])]). relacion([sujeto(['Typical', dicots, possess, 'equal-sized', cotyledons, and, 'leaf-bearing', shoots, topped, with, a, shoot, apical, meristem, '(', 'SAM),', the, source, of, lateral, 'organs,', and, where, 'KNOX1', homeobox, genes]), verbo([act]), complemento([as, key, regulators])]). relacion([sujeto(['In', all, examined, 'Lamiales', 'samples,', unlike, 'Arabidopsis,', 'BM', activity, accompanied, by, 'STM', expression, was]), verbo([found]), complemento([in, both, cotyledons, in, early, stages])]). relacion([sujeto(['An', extension, of, 'BM', activity, was]), verbo([found]), complemento([following, a, phylogenetic, trajectory, towards, 'one-leaf', plants, where, it, is, active, throughout, the, lifetime, of, the, macrocotyledon])]). relacion([sujeto(['Our', results]), verbo([suggest]), complemento([that, 'KNOX1', involvement, in, early, cotyledon, expansion, originated, early, on, in, the, diversification, of, 'Lamiales', and, is, proposed, as, the, prerequisite, for, the, evolution, of, vegetative, diversity, in, 'Gesneriaceae'])]). relacion([sujeto(['Different', 'stimuli,']), verbo([acting]), complemento([at, sites, remote, from, the, heart, '(', remote, 'conditioning),', activate, molecular, 'self-defense', mechanisms, at, the, target, organ, heart, as, well, as, in, other, parenchymal, organs])]). relacion([sujeto(['Remote', conditioning, of, the, heart]), verbo([has]), complemento([been, established, in, many, experimental, studies, and, successfully, translated, to, patients])]). relacion([sujeto(['The', present, review, focuses, on, three, levels, of, remote, conditioning, and, its, resulting, 'cardioprotection:', 'I)', at, the, stimulus, 'level,', electrical, 'stimulation,', 'chemical/pharmacological', 'substances,', mechanical, trauma, and, cycles, of, 'ischemia/reperfusion']), verbo([act]), complemento([at, sites, remote, from, the, 'heart,', 'II)', at, the, transfer, 'level,', neuronal, and, humoral, mediators, transfer, the, protective, signal, from, the, periphery, to, the, 'heart,', and, 'III)', at, the, target, 'level,', receptor, activation, and, intracellular, signal, transduction, ultimately, affect, protection, of, the, myocardium, and, other, 'organs,', as, established, in, different, animal, models, and, 'humans/patients'])]). relacion([sujeto(['Further', mechanistic, understanding, is, mandatory, to]), verbo([translate]), complemento([the, protection, by, remote, conditioning, more, successfully, to, patients, with, cardiovascular, disease])]). relacion([sujeto(['We', studied, the, 'predator-prey', interactions, between, heterotrophic, protists, and, endospores, of, 'Bacillus', cereus, group, 'bacteria,', in, order, to]), verbo([gain]), complemento([insight, on, survival, and, dispersal, of, 'B'])]). relacion([sujeto(['It']), verbo([has]), complemento([been, hypothesised, that, the, spore, stage, protects, against, digestion, by, predating, protists])]). relacion([sujeto(['These', observations, support, that, protists, can]), verbo([act]), complemento([as, a, potential, breeding, ground, for, 'B'])]). relacion([sujeto(['Unsettled', knowledge, as, to, whether, scrapie, transmits, prenatally, in, sheep, and, goats, and, transmits, by, semen, and, preimplantation, embryos]), verbo([has]), complemento([a, potential, to, compromise, measures, for, 'controlling,', preventing, and, eliminating, the, disease])]). relacion([sujeto(['Systematic', reviews]), verbo([have]), complemento([clearly, formulated, 'questions,', can, identify, relevant, studies, and, appraise, their, quality, and, can, summarise, evidence, and, reasoning, with, an, explicit, methodology])]). relacion([sujeto(['It']), verbo([leads]), complemento([to, the, second, 'question,', which, concerns, the, sanitary, safety, of, artificial, breeding, 'technologies,', and, is, whether, scrapie, transmits, in, sheep, and, goats, by, means, of, semen, and, washed, or, unwashed, in, vivo, derived, embryos])]). relacion([sujeto(['Objective:', 'Suicide', attempt, may, follow, a, process, right, from, the, inception, of, the, first, information, about, '‎suicide', until, the]), verbo([act]), complemento([itself])]). relacion([sujeto(['‎', 'Method:', 'In', this, hospital, based, 'cross-sectional', 'study,', 168, consecutive, admitted, participants, with, a, '‎suicide', attempt, were, 'screened,', and, 109, who, met, the, study, criteria, were]), verbo([recruited]), complemento([to, '‎participate', in, this, study, before, discharge])]). relacion([sujeto(['The', 'Cronbach\'s', '‎alpha', coefficient, value, of, this, questionnaire]), verbo([found]), complemento([to, be, 0.84, in, the, reliability, analysis])]). relacion([sujeto(['A', statistically, significant, negative, correlation, was]), verbo([found]), complemento([between, the, '‎source', of, the, first, information, and, education, '(', 'p<01),', any, psychiatric, diagnosis, and, duration, '‎since', the, first, death, wish, '(', 'p<01)'])]). relacion([sujeto(['One', of, the, factors]), verbo([regulating]), complemento([the, tumor, microenvironment, is, 'TNF-α,', a, pleiotropic, cytokine, that, plays, key, roles, in, 'apoptosis,', 'angiogenesis,', inflammation, and, immunity])]). relacion([sujeto(['TNF-α', can]), verbo([have]), complemento([both, 'pro-', and, 'anti-tumoral', effects, and, these, are, transmitted, via, two, major, 'receptors,', the, 55, kDa, 'TNFR1', and, the, 75, kDa, 'TNFR2', that, have, 'distinct,', as, well, as, overlapping, functions])]). relacion([sujeto(['TNFR1', is, ubiquitously]), verbo([expressed]), complemento([while, the, expression, of, 'TNFR2', is, more, 'restricted,', mainly, to, immune, cells])]). relacion([sujeto(['One', of, its, main, functions, is, to]), verbo([act]), complemento([as, a, survival, factor, and, moderate, the, 'pro-apoptotic', effects, of, 'TNFR1,', particularly, in, immune, cells])]). relacion([sujeto(['We', show, how, the, 'TNF', receptors, each, contribute, to, these, processes, by]), verbo([regulating]), complemento([and, shaping, the, tumor, microenvironment])]). relacion([sujeto(['Current', evidence, and, concepts, on, the, potential, use, of, 'TNF']), verbo([targeting]), complemento([agents, for, cancer, prevention, and, therapy, are, discussed])]). relacion([sujeto(['Independent', courses, of, experimental, evolution, with, a, recombinant, strain, lacking, 'E3L', revealed, several, high, frequency, point, mutations, in]), verbo([conserved]), complemento([poxvirus, 'genes,', suggesting, important, roles, for, essential, poxvirus, proteins, in, innate, immune, subversion])]). relacion([sujeto(['Two', distinct, mutations, were, identified, in, the, viral, 'RNA', polymerase, gene, 'A24R,', which, seem, to]), verbo([act]), complemento([through, different, mechanisms, to, increase, virus, replication])]). relacion([sujeto(['Specifically,', a, 'Leu18Phe', substitution, in, 'A24R']), verbo([conferred]), complemento([fitness, 'tradeoffs,', including, increased, activation, of, the, antiviral, factor, 'Protein', kinase, 'R', '(', 'PKR)'])]). relacion([sujeto(['Intriguingly,', this, 'A24R', variant, underwent, a, drastic, selective, sweep, during, 'passaging,', despite]), verbo([enhanced]), complemento(['PKR', activity])]). relacion([sujeto(['This', study]), verbo([reveals]), complemento([how, rapid, bouts, of, gene, copy, number, amplification, during, accrual, of, distant, point, mutations, can, potently, facilitate, poxvirus, adaptation, to, host, defenses])]). relacion([sujeto(['In', this, 'study,', we, uncovered, a, means, of, vaccinia, virus, adaptation]), verbo([involving]), complemento([the, accumulation, of, distinct, genetic, variants, within, a, single, population])]). relacion([sujeto(['We', identified, adaptive, point, mutations, in, the, viral, 'RNA', polymerase, gene, 'A24R,', and, 'surprisingly,']), verbo([found]), complemento([that, one, of, these, mutations, activates, the, nucleic, acid, sensing, factor, 'PKR'])]). relacion([sujeto(['We', also]), verbo([found]), complemento([that, gene, copy, number, variation, '(', 'CNV)', can, provide, dual, benefits, to, evolving, virus, 'populations,', including, evidence, that, 'CNV', facilitates, the, accumulation, of, a, point, mutation, distant, from, the, expanded, locus])]). relacion([sujeto(['Our', data]), verbo([suggest]), complemento([that, transient, 'CNV', can, accelerate, the, fixation, of, mutations, conferring, modest, 'benefits,', or, even, fitness, 'tradeoffs,', and, highlight, how, structural, variation, might, aid, poxvirus, adaptation, through, both, direct, and, indirect, action])]). relacion([sujeto(['Plant', 'growth,', development, and, interaction, with, the, environment]), verbo([involve]), complemento([the, action, of, multiple, phytohormones])]). relacion([sujeto(['Transcription', factors, '(', 'TFs)', of, diverse, families, play, essential, roles, in, the, signalling, cascades]), verbo([triggered]), complemento([by, the, perception, of, a, particular, hormone])]). relacion([sujeto(['TFs', may]), verbo([act]), complemento([alone, or, in, a, combinatorial, fashion, with, other, 'TFs,', and, may, act, specifically, in, a, single, hormonal, signalling, cascade, or, as, signalling, hubs, for, multiple, hormones])]). relacion([sujeto(['In', the, signalling, cascades]), verbo([triggered]), complemento([by, the, phytohormone, jasmonate, '(', 'JA),', which, modulates, a, 'diverse,', but, 'specific,', range, of, aspects, of, plant, 'growth,', development, and, 'defence,', the, 'TFs', of, the, basic, 'helix-loop-helix', '(', 'bHLH)', family, play, an, essential, and, often, conserved, role, in, the, plant, kingdom])]). relacion([sujeto(['Here,', we, first, discuss, the, bHLH, 'TFs']), verbo([involved]), complemento([in, all, kinds, of, 'JA-modulated', processes, in, the, model, plant, 'Arabidopsis', thaliana, 'Secondly,', we, elaborate, on, the, identity, and, role, of, bHLH, 'TFs', in, the, conserved, 'JA-mediated', elicitation, of, specialized, metabolism, of, medicinal, and, crop, species])]). relacion([sujeto(['Finally,', we, discuss, which, directions, future, fundamental, research, on, the, functioning, of, bHLH, 'TFs', in, 'JA', signalling, may, head, for, and, how, this, research, can, be]), verbo([translated]), complemento([from, model, plants, into, crop, and, medicinal, plant, species, to, engineer, traits, of, agronomical, and, industrial, interest])]). relacion([sujeto(['Anthocyanins,', a, class, of, 'flavonoids,', are, responsible, for, the, orange, to, blue, coloration, of, flowers, and]), verbo([act]), complemento([as, visual, attractors, to, aid, pollination, and, seed, dispersal])]). relacion([sujeto(['Previous', studies]), verbo([have]), complemento([suggested, that, 'malonyl-CoA', is, formed, almost, exclusively, by, 'acetyl-CoA', 'carboxylase,', which, catalyzes, the, 'ATP-dependent', formation, of, 'malonyl-CoA', from, 'acetyl-CoA', and, bicarbonate])]). relacion([sujeto(['Virus-induced', gene, silencing, of, petunia, 'PhAAE13', significantly, reduced, anthocyanin, 'accumulation,', fatty, acid, 'content,', and, cuticular, wax, components, 'content,', and]), verbo([increased]), complemento([malonic, acid, content, in, flowers])]). relacion([sujeto(['This', study]), verbo([provides]), complemento([strong, evidence, indicating, that, 'PhAAE13,', among, clade, 'VII', of, the, 'AAE', 'superfamily,', is, specifically, involved, in, anthocyanin, biosynthesis, in, petunia, flowers])]). relacion([sujeto(['Social', interventions]), verbo([targeted]), complemento([at, people, with, severe, mental, illness, '(', 'SMI)', often, include, volunteers])]). relacion([sujeto(['However,', the, families, often, doubted, their, personal, judgement, and, relied, on, mental, health, workers, to]), verbo([act]), complemento([as, safety, net])]). relacion([sujeto(['This', article, discusses, how, to, recognise, and, approach, the, diagnosis, of, patients, suspected, to]), verbo([have]), complemento([symptoms, of, abnormal, mast, cell, activation])]). relacion([sujeto(['Given', the, highly, varied, and, often, complex, symptomatology, of, such, 'patients,', we, advocate, applying, a, logical, 'step-wise', approach, to, investigating, these, patients, to]), verbo([ensure]), complemento([the, correct, diagnosis, is, made])]). relacion([sujeto(['Treatments', of, mast, cell, activation, disorders, are, 'discussed,', dividing, them, into, those, that, ameliorate, the, effects, of, mast, cell, mediators, and, those, that]), verbo([act]), complemento([to, stabilise, the, mast, cell])]). relacion([sujeto(['Whether', 'non-nutrient', secretagogues]), verbo([stimulate]), complemento([mitochondria, as, part, of, the, molecular, mechanism, to, promote, insulin, secretion, is, not, known])]). relacion([sujeto(['A', range, of, inhibitors, of, novel, 'PKC', isoforms]), verbo([prevent]), complemento([phorbol, 'ester-induced', respiration])]). relacion([sujeto(['Enhanced', respiration, was, observed, even, when, glycolysis, was, bypassed, or, fatty, acid, transport, was, 'blocked,', which]), verbo([suggested]), complemento([that, 'PKC', regulates, mitochondrial, processes, rather, than, upstream, catabolic, fluxes])]). relacion([sujeto(['A', phosphoproteome, study, of, phorbol, 'ester-stimulated', 'INS-1E', cells]), verbo([maintained]), complemento([under, resting, '(', 2.5, 'mM)', glucose, revealed, a, large, number, of, phosphorylation, sites, that, were, altered, during, 'short-term', activation, of, 'PKC', signaling])]). relacion([sujeto(['The', data, set, was, enriched, for, proteins, that, are]), verbo([involved]), complemento([in, gene, 'expression,', cytoskeleton, 'remodeling,', secretory, vesicle, 'transport,', and, exocytosis])]). relacion([sujeto(['Prevention', of, 'ERK1/2', signaling, by, using, a, 'MEK1', inhibitor]), verbo([caused]), complemento([a, marked, decreased, in, phorbol, 12, -, myristate, 13, -, 'acetate-induced', mitochondrial, respiration])]). relacion([sujeto(['We', conclude, that, 'non-nutrient', secretagogues, 'act,', in, 'part,', via, 'PKC', and, downstream, 'ERK1/2', signaling, to]), verbo([stimulate]), complemento([mitochondrial, energy, production, to, compensate, for, energy, expenditure, that, is, linked, to, 'β-cell', activation])]). relacion([sujeto(['Coordinated', activation, of, mitochondrial, respiration, and, exocytosis]), verbo([mediated]), complemento([by, 'PKC', signaling, in, pancreatic, 'β-cells'])]). relacion([sujeto(['Retrospective', review, of, prospectively]), verbo([maintained]), complemento([database])]). relacion([sujeto(['Because', of, posterior, element, abnormality, in, 'myelomeningocele,', the, extensor, muscles]), verbo([act]), complemento([as, perverted, 'flexors,', driving, progressive, kyphosis, that, resulted, in, 'sitting,', 'respiratory,', and, skin, breakdown, problems])]). relacion([sujeto(['The', median, surgical, time, was, 245, minutes, '(', 165, -, 285, ')', ',', with, an, estimated, blood]), verbo([loss]), complemento([of, 700, mL, '(', 500, -, 2, ',', 550, ')'])]). relacion([sujeto(['Although', an, infrequent, presentation, 'today,', severe, kyphosis, in, myelomeningocele, patients]), verbo([causes]), complemento([not, only, a, major, functional, impairment, but, threat, to, their, life, with, apical, pressure, sores])]). relacion([sujeto(['National', 'Notifiable', 'Diseases', 'Surveillance', 'System', data, were, analysed, for, the, period, 1991, -, 2014, ',', along, with]), verbo([enhanced]), complemento([risk, factor, data, from, notified, cases, in, the, states, of, 'New', 'South', 'Wales', and, 'Queensland,', to, examine, changes, in, the, epidemiology, of, 'Q', fever, in, 'Australia'])]). relacion([sujeto(['The', national, 'Q', fever, notification, rate, reduced, by, 20, '%', '[', incident, rate, ratio, '(', 'IRR)', 0, '·82]', following, the, end, of, the, 'National', 'Q', fever, 'Management', 'Program', in, 2006, ',', and]), verbo([has]), complemento([increased, since, 2009, '(', 'IRR', 1, '·01-1·34)'])]). relacion([sujeto(['The', age, of, 'Q', fever, cases, and, proportion, of, females]), verbo([increased]), complemento([over, the, study, period])]). relacion([sujeto(['Based', on, the]), verbo([enhanced]), complemento([risk, factor, 'data,', the, most, frequently, listed, occupation, for, 'Q', fever, cases, involved, contact, with, 'livestock,', followed, by, '\'', no, known, 'risk\'', occupations])]). relacion([sujeto(['More', complete, and, comparable]), verbo([enhanced]), complemento([risk, factor, 'data,', at, the, 'State/Territory', and, national, 'levels,', would, aid, in, further, understanding, of, the, epidemiology, of, 'Q', fever])]). relacion([sujeto(['Wheat', stem, 'rust,']), verbo([caused]), complemento([by, 'Puccinia', graminis, f])]). relacion([sujeto(['tritici,', is, a, major, wheat, disease, which, is, mainly, controlled, through, the]), verbo([release]), complemento([of, resistant, cultivars, containing, one, or, several, resistance, genes])]). relacion([sujeto(['Considerable', effort]), verbo([has]), complemento([been, put, into, the, discovery, of, new, resistance, 'genes,', but, knowledge, of, their, mechanisms, of, action, is, often, lacking])]). relacion([sujeto(['In', this, 'study,', the, mechanism, of, resistance]), verbo([conferred]), complemento([by, a, recently, discovered, stem, rust, resistance, locus, on, wheat, chromosome, 7, 'AL', was, investigated, through, microscopic, observations, and, 'RNA-sequencing,', using, the, susceptible, line, 'Columbus', and, the, 'independent,', 'backcrossed,', resistant, lines, 'Columbus-NS765', and, 'Columbus-NS766'])]). relacion([sujeto(['Microscopic', observations, of, infected, leaves, revealed, that, the, resistance]), verbo([conferred]), complemento([by, the, 7, 'AL', resistance, locus, was, initiated, 2, &, 'nbsp;days', 'post-inoculation,', upon, the, fungus, entry, into, the, plant, through, the, stoma])]). relacion([sujeto(['Occasionally,', similar, observations, were, made, in, the, susceptible, 'line,']), verbo([suggesting]), complemento([that, the, resistance, response, was, the, same, in, all, 'genotypes,', but, enhanced, in, the, resistant, lines])]). relacion([sujeto(['Transcriptomic', 'analysis,', combined, with, assignment, of, genes, to, wheat, 'chromosomes,', revealed, a, disproportionately, high, number, of, differentially]), verbo([expressed]), complemento([genes, were, located, on, chromosomes, 7, 'AL', and, 6, 'A'])]). relacion([sujeto(['The', results, also, indicated, the, presence, of, a, large, introgression, on, chromosome, 6, 'A', in, both, resistant, 'lines,', but, whether, it]), verbo([has]), complemento([any, role, in, the, resistance, response, is, unclear])]). relacion([sujeto(['This', study, represents, the, first, investigation, on, the, resistance, mechanism]), verbo([conferred]), complemento([by, the, wheat, 7, 'AL', stem, rust, resistance, locus])]). relacion([sujeto(['The', resistance, response, was]), verbo([associated]), complemento([with, 'pre-haustorial', cell, 'death,', and, the, transcriptome, analysis, suggested, putative, 'receptor-like', cytoplasmic, kinases, as, candidate, resistance, genes, for, further, investigation])]). relacion([sujeto(['Health', and, fitness, applications, '(', 'apps)']), verbo([have]), complemento([gained, popularity, in, interventions, to, improve, 'diet,', physical, activity, and, sedentary, behaviours, but, their, efficacy, is, unclear])]). relacion([sujeto(['Twenty-three', studies]), verbo([targeted]), complemento([adults, '(', 17, showed, significant, health, 'improvements)', and, four, studies, targeted, children, '(', two, demonstrated, significant, health, 'improvements)'])]). relacion([sujeto(['Twenty-one', studies]), verbo([targeted]), complemento([physical, activity, '(', 14, showed, significant, health, 'improvements),', 13, studies, targeted, diet, '(', seven, showed, significant, health, 'improvements)', and, five, studies, targeted, sedentary, behaviour, '(', two, showed, significant, health, 'improvements)'])]). relacion([sujeto(['More', studies, '(', n, =, 12, ;, 63, '%', ')', of, those]), verbo([reporting]), complemento([significant, effects, detected, 'between-group', improvements, in, the, health, behaviour, or, related, health, 'outcomes,', whilst, fewer, studies, '(', n, =, 8, ;, 42, '%', ')', reported, significant, 'within-group', improvements])]). relacion([sujeto(['Eleven', studies]), verbo([reported]), complemento([app, usage, 'statistics,', and, three, of, them, demonstrated, that, higher, app, usage, was, associated, with, improved, health, outcomes])]). relacion([sujeto(['This', review]), verbo([provided]), complemento([modest, evidence, that, 'app-based', interventions, to, improve, 'diet,', physical, activity, and, sedentary, behaviours, can, be, effective])]). relacion([sujeto(['(', 'Asteraceae)']), verbo([has]), complemento([been, reported, to, be, a, nerve, tonic, and, has, been, used, to, treat, epilepsy, in, folk, medicine])]). relacion([sujeto([alba, and, evaluates, its, antiepileptic, potential, in, chemically]), verbo([induced]), complemento([acute, and, chronic, models, in, mice])]). relacion([sujeto(['Kindling', was]), verbo([induced]), complemento([by, chronic, administration, of, 'PTZ', '(', 35, 'mg/kg)', on, every, alternate, day, '(', 48, 'days)'])]). relacion([sujeto([')', was]), verbo([found]), complemento([to, be, effective, in, an, acute, 'PTZ', model, '(', 100, '%', protection, from, 'mortality)', and, it, did, not, exhibit, any, effect, on, motor, coordination, at, the, same, doses])]). relacion([sujeto(['PTZ-induced', kindling, was, significantly, '(', p, &, 'lt;', 0.001, ')']), verbo([prevented]), complemento([by, luteolin, '(', 5, ',', 10, ',', 20, 'mg/kg,', i])]). relacion([sujeto(['Luteolin', restored, levels, of, reduced, 'GSH', '(', p, &, 'lt;', 0.001, ')', and]), verbo([decreased]), complemento([the, level, of, 'MDA', '(', p, &, 'lt;', 0.001, ')', ',', a, marker, of, lipid, peroxidation])]). relacion([sujeto(['Luteolin', exhibited, and, inhibitory, effect, on, the, course, of, kindling, and]), verbo([associated]), complemento([oxidative, stress, and, hence, could, be, a, potential, molecule, in, the, treatment, of, epilepsy])]). relacion([sujeto(['NURSES', 'COULD', face, legal, risks, under, the, 'Human', 'Rights', 'Act', by, using, '\'', pain, 'compliance\'', techniques, to, restrain, 'patients,', a]), verbo([leading]), complemento([researcher, has, warned])]). relacion([sujeto(['Nurses', do, not, need, to]), verbo([have]), complemento([responsibilities, 'delegated;', they, must, be, able, to, carry, out, assessments, and, provide, care, and, treatment, in, their, own, right])]). relacion([sujeto(['This', will, work, better]), verbo([provided]), complemento([that, nurses, recognise, and, act, on, the, importance, of, '\'', 'real\'', professional, skills, development])]). relacion([sujeto(['Last', january, the, 'Guardian']), verbo([reported]), complemento([that, '\'', the, 'NHS', is, in, an, impossible, situation, which, endless, reforms, have, failed, to, 'address\''])]). relacion([sujeto(['It', explores, the, impact, the, 'Act', will]), verbo([have]), complemento([on, key, areas, such, as, health, 'law,', ethics, and, 'patients\'', rights])]). relacion([sujeto(['This', collateral, damage, to, cellular, proteins]), verbo([has]), complemento([been, termed, '\'', 'bystander\'', mechanism])]). relacion([sujeto(['How', a, single, misfolded, protein, overwhelms, the, 'proteostasis,', and, how, 'broadly-expressed', mutant, proteins]), verbo([cause]), complemento([cell, 'type-selective', phenotypes, in, disease, are, open, questions])]). relacion([sujeto(['DAF-28(R37C)', is, broadly, 'expressed,', but, only]), verbo([causes]), complemento([dysfunction, in, one, specific, 'neuron,', 'ASI,', leading, to, a, distinct, developmental, phenotype])]). relacion([sujeto(['We']), verbo([find]), complemento([that, this, phenotype, is, caused, by, selective, disruption, of, normal, biogenesis, of, an, unrelated, endogenous, 'protein,', 'DAF-7/TGF-β'])]). relacion([sujeto(['Using', 'functional,', 'fluorescently-tagged', 'protein,', we]), verbo([find]), complemento(['that,', in, animals, with, mutant, 'DAF-28/IGF,', the, 'wild-type', 'DAF-7/TGF-β', is, mislocalized, to, and, accumulates, in, the, proximal, axon, of, the, 'ASI', neuron])]). relacion([sujeto(['Activation', of, two, different, branches, of, the, unfolded, protein, response, can]), verbo([modulate]), complemento([both, the, developmental, phenotype, and, 'DAF-7', mislocalization, in, 'DAF-28(R37C)', 'animals,', but, appear, to, act, through, divergent, mechanisms])]). relacion([sujeto(['Our']), verbo([finding]), complemento([that, bystander, targeting, of, 'TGF-β', explains, the, phenotype, caused, by, a, folding, mutation, in, an, 'IGF-like', protein, suggests, 'that,', in, conformational, 'diseases,', bystander, misfolding, may, specify, the, distinct, phenotypes, caused, by, different, folding, mutations])]). relacion([sujeto(['Using', chemical, genetic, and, optogenetic, 'tools,', we, demonstrate, that, the, association, of, 'ECT2', with, the, plasma, membrane, during, anaphase, is]), verbo([required]), complemento([and, sufficient, for, cytokinesis])]). relacion([sujeto(['Local', membrane]), verbo([targeting]), complemento([of, 'ECT2', leads, to, unilateral, 'furrowing,', highlighting, the, importance, of, local, 'ECT2', activity])]). relacion([sujeto(['ECT2', mutations, that]), verbo([prevent]), complemento([centralspindlin, binding, compromise, concentration, of, 'ECT2', at, the, midzone, and, equatorial, membrane, but, sustain, cytokinesis])]). relacion([sujeto(['While', the, association, of, 'ECT2', with, the, plasma, membrane, is, essential, for, 'cytokinesis,', our, data]), verbo([suggest]), complemento([that, 'ECT2', recruitment, to, the, spindle, midzone, is, insufficient, to, account, for, equatorial, furrowing, and, may, act, redundantly, with, 'yet-uncharacterized', signals])]). relacion([sujeto(['In', developing, 'epithelia,', the, core, planar, polarity, proteins, physically]), verbo([interact]), complemento([with, each, other, and, localize, asymmetrically, at, opposite, cell, 'ends,', forming, intercellular, complexes, that, link, the, polarity, of, neighboring, cells])]). relacion([sujeto(['Using', quantitative, imaging, to, examine, the, composition, of, the, core, protein, complex, 'in vivo,', we]), verbo([find]), complemento([that, complex, composition, is, unexpectedly, plastic])]). relacion([sujeto(['Exploring', the, functional, consequences, of, 'this,', we, show, that, robust, cell, polarization, is, achieved, over, a, range, of, complex, stoichiometries, but, is, dependent, on]), verbo([maintaining]), complemento([appropriate, levels, of, the, components, 'Frizzled', and, 'Strabismus'])]). relacion([sujeto(['We', propose, that, the, core, proteins, assemble, into, 'signalosome-like', 'structures,', where, stable, association, is, not, dependent, on, 'one-to-one', interactions, with]), verbo([binding]), complemento(['partners,', and, signaling, functions, can, act, over, a, wide, range, of, complex, compositions])]). relacion([sujeto(['Plant', glutamate, receptor, homologs, '(', 'GLRs)']), verbo([have]), complemento([long, been, proposed, to, function, as, 'ligand-gated', 'Ca(2+)', 'channels,', but, no, in, planta, evidence, has, been, provided])]). relacion([sujeto([5, form, 'Ca(2+)', channels]), verbo([activated]), complemento([by, 'L-methionine', '(', 'L-Met)', at, physiological, concentrations, and, regulate, stomatal, apertures, and, plant, growth])]). relacion([sujeto([1, /, 3.5, mutations, resulted, in, a, lower, cytosolic, 'Ca(2+)', 'level,', defective, 'Ca(2+)-induced', stomatal, 'closure,', and, 'Ca(2+)-deficient', growth, 'disorder,', all, of, which]), verbo([involved]), complemento(['L-Met'])]). relacion([sujeto([1, /, 3.5, 'Ca(2+)', channels, are]), verbo([activated]), complemento([specifically, by, 'L-Met,', with, the, activation, abolished, in, glr3])]). relacion([sujeto([1, /, 3.5, 'Ca(2+)', channels, are, distinct, from, previously, characterized, 'ROS-activated', 'Ca(2+)', channels, and]), verbo([act]), complemento([upstream, of, 'ROS,', providing, 'Ca(2+)', transients, necessary, for, the, activation, of, 'NADPH', oxidases])]). relacion([sujeto([1, /, 3.5, constitute, 'L-Met-activated', 'Ca(2+)', channels, responsible, for]), verbo([maintaining]), complemento([basal, '[', 'Ca(2+)]cyt,', play, a, pivotal, role, in, plant, 'growth,', and, act, upstream, of, 'ROS,', thereby, regulating, stomatal, aperture])]). relacion([sujeto(['Studies', were, excluded, if, they, were, conducted, outside, the, 'United', 'States,', focused, on, recent, immigrant, 'populations,', or, 'didn\'t']), verbo([have]), complemento([an, 'English-language', abstract])]). relacion([sujeto(['A', total, of, 7, studies, was]), verbo([retained]), complemento([for, 'review-3', on, the, experience, of, patients, and, 4, on, the, experience, of, providers])]). relacion([sujeto(['Racism', and, 'midwifery\'s', lack, of, racial, diversity]), verbo([act]), complemento([as, a, barrier, to, people, of, color, completing, midwifery, education, programs, and, fully, participating, in, midwifery, professional, organizations])]). relacion([sujeto(['Both', patients, and, midwives, of, color, identified, midwives, of, color, as, uniquely, positioned, to]), verbo([provide]), complemento(['high-quality', care, for, communities, of, color])]). relacion([sujeto(['The', midwifery, profession, and, its, patients, stand, to, substantially, benefit, from, diversification, of, the, 'field,', which]), verbo([requires]), complemento([addressing, racism, within, the, profession])]). relacion([sujeto(['New', 'quality-based', reimbursements, tied, to, readmissions, call, for, a, better, understanding, of, the]), verbo([causes]), complemento([of, readmission, after, procedures, such, as, lumbar, discectomy])]). relacion([sujeto(['Factors', most]), verbo([associated]), complemento([with, readmission, after, lumbar, discectomy, were, higher, 'ASA', class, '(', 'Relative', risk, '[', 'RR]', =, 1.49, ',', p, &, 'lt;', 0.001, ')', and, prolonged, operative, time, '(', 'RR', =, 1.41, ',', p, =, 0.002, ')'])]). relacion([sujeto(['Environmental', 'stress,', such, as, oxidative, or, heat, 'stress,']), verbo([induces]), complemento([the, activation, of, the, heat, shock, response, '(', 'HSR)', and, leads, to, an, increase, in, the, heat, shock, proteins, '(', 'HSPs)', level])]). relacion([sujeto(['These', 'HSPs']), verbo([act]), complemento([as, molecular, chaperones, to, maintain, cellular, proteostasis])]). relacion([sujeto(['Germ', 'line-specific', genes, are]), verbo([activated]), complemento([in, somatic, cells, during, 'tumorigenesis,', and, are, accordingly, referred, to, as, cancer, germline, genes])]). relacion([sujeto(['Such', genes, that]), verbo([act]), complemento([on, piRNA, '(', 'Piwi-interacting', 'RNA)', processing, play, an, important, role, in, the, progression, of, cancer, cells])]). relacion([sujeto(['Here,', we, show, that, the, spermatogenic, transposon, silencer, maelstrom, '(', 'Mael),', a, 'piRNA-processing', 'factor,', is]), verbo([required]), complemento([for, malignant, transformation, and, survival, of, cancer, cells])]). relacion([sujeto(['A', specific, 'Mael', isoform, was, distinctively, overexpressed, in, diverse, human, cancer, cell, lines, and, its, depletion, resulted, in, 'cancer-specific', cell, 'death,', characterized, by, apoptosis, and, 'senescence,', accompanied, by, an]), verbo([increase]), complemento([in, reactive, 'oxygen-species', and, 'DNA', damage])]). relacion([sujeto(['These', biochemical, changes, and, death, phenotypes]), verbo([induced]), complemento([by, 'Mael', depletion, were, dependent, on, 'ATM'])]). relacion([sujeto(['Interestingly', 'Mael', was, essential, for, 'Myc/Ras-induced', 'transformation,', and, its, overexpression]), verbo([inhibited]), complemento(['Ras-induced', senescence])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, 'Mael', depletion, induces, 'ATM-dependent', 'DNA', 'damage,', consequently, leading, to, cell, death, specifically, in, cancer, cells])]). relacion([sujeto(['Over', the, last, couple, of, 'decades,', a, body, of, theories]), verbo([has]), complemento([emerged, that, explains, when, and, why, people, are, motivated, to, act])]). relacion([sujeto(['Multiple', disciplines]), verbo([have]), complemento([investigated, the, origins, and, consequences, of, motivated, 'behavior,', and, have, done, so, largely, in, parallel])]). relacion([sujeto(['Only', recently]), verbo([have]), complemento([different, 'disciplines,', like, psychology, and, 'economics,', begun, to, consolidate, their, 'knowledge,', attempting, to, integrate, findings])]). relacion([sujeto(['Though', monetary, incentives, are, pivotal, in, traditional, economic, 'theory,', biological, and, psychological, theories, ascribe, less, significance, to, monetary, incentives, and]), verbo([suggest]), complemento([alternative, drivers, for, motivation])]). relacion([sujeto(['The', amount, of, precompression, needed, to]), verbo([decrease]), complemento([the, number, of, color, pixels, by, 50, '%', and, 100, '%', was, calculated])]). relacion([sujeto(['The', mean, percentages, of, precompression, ±, 'SD', needed, to]), verbo([decrease]), complemento([the, number, of, color, voxels, by, 50, '%', in, were, 15.9, '%', ±, 6.43, '%', '(', 'range,', 8, '%', -, 30, '%', ')', for, benign, lesions, and, 14.0, '%', ±, 4.17, '%', '(', 'range,', 8, '%', -, 20, '%', ')', for, malignant, lesions, '(', 'P', =])]). relacion([sujeto(['The', percentages, of, precompression, needed, to]), verbo([decrease]), complemento([the, number, of, color, pixels, by, 100, '%', in, were, 34.7, '%', ±, 12.33, '%', '(', 'range,', 23, '%', -, 62, '%', ')', for, benign, lesions, and, for, malignant, lesions, 26.7, '%', ±, 3.89, '%', '(', 'range,', 18, '%', -, 31, '%', ')', ',', which, were, statistically, significant, '(', 'P', =])]). relacion([sujeto(['The', amount, of, precompression, normally, used, when, obtaining, 'B-mode', images, can, substantially]), verbo([decrease]), complemento([the, number, of, color, voxels, on, power, 'Doppler', sonography])]). relacion([sujeto(['Replacing', formic, acid, with, molecular, hydrogen, or, isopropanol]), verbo([decreased]), complemento([the, oil, yield, to, a, considerable, 'degree,', increased, the, solid, yield, and, altered, the, nature, of, the, 'bio-oil'])]). relacion([sujeto(['The', differences]), verbo([induced]), complemento([by, the, presence, of, molecular, hydrogen, were, comparable, to, the, ones, observed, in, the, isopropanol, 'system,', suggesting, similar, lignin, conversion, mechanisms, for, both, systems])]). relacion([sujeto(['Additional', 'semi-batch', experiments, confirmed, that, formic, acid, does, not]), verbo([act]), complemento([merely, as, an, in, situ, hydrogen, source, or, hydrogen, donor, molecule])]). relacion([sujeto(['On', the, 'contrary,', formic, acid, seems, to, react, with, lignin, through, a, 'formylation-elimination-hydrogenolysis', mechanism, that]), verbo([leads]), complemento([to, the, 'de-polymerization', of, the, biopolymer])]). relacion([sujeto(['To', the, best, of, our, 'knowledge,', this, is, the, first, time, that, the, distinctive, 'role/mechanism', of, formic, acid]), verbo([has]), complemento([been, observed, in, the, conversion, of, real, lignin, feedstock])]). relacion([sujeto(['Current', methods, of, measuring, constructs, in, the, 'PWM', rely, on, 'self-report,', thus]), verbo([require]), complemento([a, level, of, conscious, deliberation])]). relacion([sujeto(['The', study]), verbo([involved]), complemento([a, 'cross-sectional', design])]). relacion([sujeto(['Evidence', also]), verbo([suggests]), complemento([that, risky, drinking, in, young, people, may, be, influenced, by, implicit, attitudes, towards, 'alcohol,', which, develop, with, repeated, exposure, to, alcohol, over, time])]). relacion([sujeto(['One', criticism, of, the, 'PWM', is, that, prototypes, and, willingness, are, usually, measured, using, explicit, measures, which, may, not, adequately, capture, young, 'people\'s', spontaneous, evaluations, of, 'prototypes,', or, their, propensity, to]), verbo([act]), complemento([without, forethought, in, a, social, context])]). relacion([sujeto(['Findings']), verbo([suggest]), complemento([that, adding, implicit, alcohol, attitudes, into, the, 'PWM', might, be, able, to, explain, the, shift, from, reactive, to, intentional, drinking, behaviours, with, age, and, experience])]). relacion([sujeto(['Genes', encoding, cellular, membrane, trafficking, 'components,', namely, 'RAB7L1', and, 'RAB39B,', are, more, recently]), verbo([recognized]), complemento([factors, associated, with, 'Parkinson\'s', disease, '(', 'PD)'])]). relacion([sujeto(['Encoded', by, a, gene, within, the, 'PARK16', 'locus,', 'RAB7L1']), verbo([interacts]), complemento([with, 'Leucine-rich', repeat, kinase, 2, '(', 'LRRK2)', to, act, in, intracellular, transport, processes, that, are, likely, important, in, neuronal, survival, and, function])]). relacion([sujeto(['LRRK2', also, directly]), verbo([phosphorylates]), complemento([a, number, of, other, 'Rab', proteins])]). relacion([sujeto(['The', cellular, or, neuronal, functions, of, 'RAB39B', are, not, yet, known, with, 'certainty,', but, it]), verbo([has]), complemento([recently, been, shown, to, play, a, role, in, glutamate, receptor, trafficking])]). relacion([sujeto(['In', this, 'review,', we, discuss, the, association, of, 'Rabs', with, 'PD', 'pathology,', and, potential, etiological, mechanisms, whereby, defects, or, deficiencies, in, certain, 'Rab', proteins, could]), verbo([lead]), complemento([to, 'PD', susceptibility])]). relacion([sujeto(['The', objective, was, to, determine, whether, 'CD52', lymphocyte, depletion, can]), verbo([act]), complemento([to, promote, immunological, tolerance, induction, via, intravenous, antigen, administration, such, that, it, could, be, used, to, 'either:', improve, efficiency, of, inhibition, of, 'MS', or, to, inhibit, secondary, autoimmunities, that, may, occur, following, alemtuzumab, use, in, multiple, sclerosis])]). relacion([sujeto(['Relapsing', experimental, autoimmune, encephalomyelitis, was]), verbo([induced]), complemento([in, 'ABH', mice, and, immune, cell, depletion, was, therapeutically, applied, using, mouse, 'CD52', or, 'CD4', '(', in, conjunction, with, 'CD8', or, 'CD20)', depleting, monoclonal, antibodies])]). relacion([sujeto(['Immunological', unresponsiveness, was, then, subsequently]), verbo([induced]), complemento([using, intravenous, central, nervous, system, antigens, and, responses, assessed, clinically])]). relacion([sujeto(['However,', more, marked, '(', '~75-90%)', physical, depletion, 'CD4', 'T', cells, via, 'CD4', and, 'CD52', depleting, antibodies]), verbo([inhibited]), complemento([relapsing, disease])]). relacion([sujeto(['Surprisingly', in, contrast, to, 'CD4', 'depletion,', 'CD52', depletion, blocked, robust, immunological, unresponsiveness, via, a, mechanism]), verbo([involving]), complemento(['CD8', 'T', cells])]). relacion([sujeto(['Although', efficacy, was, related, to, the, level, of, 'CD4', 'T', cell, 'depletion,', the, observations, that, 'CD52', depletion, of, 'CD19', 'B', cells, was, less, marked, in, lymphoid, organs, than, in, the, blood]), verbo([provides]), complemento([a, rational, for, the, rapid, 'B', cell, 'hyper-repopulation', that, occurs, following, alemtuzumab, administration, in, 'MS'])]). relacion([sujeto(['That', 'B', cells, repopulate, in, the, relative, absence, of, 'T', cell, regulatory, mechanisms, that]), verbo([promote]), complemento([immune, tolerance, may, account, for, the, secondary, 'B', cell, 'autoimmunities,', which, occur, following, alemtuzumab, treatment, of, multiple, sclerosis])]). relacion([sujeto(['Toxoplasma', gondii, is, an, intracellular, protozoan, with, worldwide, distribution, and, dogs]), verbo([act]), complemento([as, sentinels, of, human, infection])]). relacion([sujeto([gondii, in, dogs, of, the, communities, on, the, 'Cuiabá', 'River,', 'Mato', 'Grosso', and, variables]), verbo([associated]), complemento([with, infection])]). relacion([sujeto(['The', prevalence, and, factors]), verbo([associated]), complemento([with, infection, were, calculated, by, 'chi-squared', test, '(', 'χ2)', or, 'Fisher\'s', exact, 'test,', and, univariate, and, multiple, analysis])]). relacion([sujeto(['As', for, the]), verbo([associated]), complemento(['factors,', the, only, statistically, significant, factor, was, that, of, dogs, living, with, cats, '(', p, =, 0.02, ')', ',', with, approximately, twice, the, risk, of, acquiring, infection])]). relacion([sujeto(['In', 'conclusion,', the, seroprevalence, in, dogs, of, riverside, communities, in, the, 'Baixada', 'Cuiabana', demonstrated, that, high, rates, of, 'infection,', being, the, factor]), verbo([associated]), complemento([with, 'infection,', contact, with, domestic, cats])]). relacion([sujeto(['Neighborhood', dogs, may]), verbo([act]), complemento([as, reservoirs, for, several, zoonotic, protozoan, 'infections,', particularly, in, urban, 'areas,', thus, constituting, a, potential, public, health, threat])]). relacion([sujeto(['Pathogen', seroreactivity, was, not]), verbo([associated]), complemento([with, the, daily, human, movements, or, other, epidemiological, variables, investigated, '(', p, &, 'gt;', 0.05, ')'])]). relacion([sujeto(['The', homeodomain, transcription, factor, 'distal-less', homeobox, 3, gene, '(', 'DLX3)', is]), verbo([required]), complemento([for, 'hair,', tooth, and, skeletal, development])]). relacion([sujeto(['DLX3', mutations]), verbo([have]), complemento([been, found, to, be, responsible, for, 'Tricho-Dento-Osseous', '(', 'TDO)', 'syndrome,', characterized, by, kinky, 'hair,', 'thin-pitted', enamel, and, increased, bone, density])]). relacion([sujeto([533, 'A>G;', 'Q178R)', attenuates, osteogenic, potential, and, senescence, of, bone, mesenchymal, stem, cells, '(', 'BMSCs)', isolated, from, a, 'TDO', 'patient,']), verbo([providing]), complemento([a, molecular, explanation, for, abnormal, increased, bone, density])]). relacion([sujeto(['Furthermore,', the, attenuated, skeletal, aging, and, bone]), verbo([loss]), complemento([in, 'DLX3', '(', 'Q178R)', transgenic, mice, not, only, reconfirmed, that, 'DLX3', mutation, '(', 'Q178R)', delayed, cellular, 'senescence,', but, also, prevented, 'aging-mediated', bone, loss])]). relacion([sujeto(['Taken', 'together,', these, results, indicate, that, 'DLX3', mutations]), verbo([act]), complemento([as, a, loss, of, function, in, senescence])]). relacion([sujeto(['The', delayed, senescence, of, 'BMSCs']), verbo([leads]), complemento([to, increased, bone, formation, by, compensating, decreased, osteogenic, potentials, with, more, generations, and, extended, functional, lifespan])]). relacion([sujeto(['Our', findings, in, the, rare, human, genetic, disease, unravel, a, novel, mechanism, of, 'DLX3']), verbo([involving]), complemento([the, senescence, regulation, of, bone, formation])]). relacion([sujeto(['Because', torque, teno, virus, '(', 'TTV)']), verbo([has]), complemento([been, implicated, in, tumorigenesis, as, a, 'cocarcinogen,', we, studied, 'TTV', prevalence, in, saliva, and, biopsy, samples, from, head, and, neck, cancer, '(', 'HNCC)', 'patients,', patients, with, premalignant, lesions, of, oral, 'cancer,', and, controls])]). relacion([sujeto(['By', phylogenetic, 'analysis,', 'TTV', belonging, mostly, to, genotypes, 1, and, 2, was]), verbo([found]), complemento([in, 'HNCC', patients])]). relacion([sujeto(['Our', data, are, compatible, with, the, idea, that, 'TTV', might]), verbo([act]), complemento([as, a, cocarcinogen, in, certain, cases, of, 'HNCC'])]). relacion([sujeto(['Alcohol', dependency]), verbo([has]), complemento([deleterious, effects, on, empathy, 'ability,', and, cognitive, and, emotional, functions])]). relacion([sujeto(['Empathy', ability]), verbo([has]), complemento([strong, relationships, with, cognitive, and, emotional, functions])]). relacion([sujeto(['The', past, three, decades]), verbo([have]), complemento([witnessed, an, enormous, progress, in, the, elucidation, of, the, 'ERK/MAPK', signaling, pathway, and, its, involvement, in, various, cellular, processes])]). relacion([sujeto(['Because', of, its, importance, and, complex, 'wiring,', the, 'ERK', pathway]), verbo([has]), complemento([been, an, intensive, subject, for, mathematical, 'modeling,', which, facilitates, the, unraveling, of, key, dynamic, properties, and, behaviors, of, the, pathway])]). relacion([sujeto(['Recently,', 'however,', it, became, evident, that, the, pathway, does, not]), verbo([act]), complemento([in, isolation, but, closely, interacts, with, many, other, pathways, to, coordinate, various, cellular, outcomes, under, different, pathophysiological, contexts])]). relacion([sujeto(['This']), verbo([has]), complemento([led, to, an, increasing, number, of, 'integrated,', 'large-scale', models, that, link, the, 'ERK', pathway, to, other, functionally, important, pathways])]). relacion([sujeto(['We', then, use, three, examples, of, 'integrated,', multipathway, models, to, investigate, how, crosstalk, of, 'ERK', signaling, with, other, pathways]), verbo([regulates]), complemento(['cell-fate', 'decision-making', in, various, physiological, and, disease, contexts])]). relacion([sujeto(['We', conclude, that, integrated, modeling, in, combination, with, 'wet-lab', experimentation]), verbo([have]), complemento([been, and, will, be, instrumental, in, gaining, an, 'in-depth', understanding, of, 'ERK', signaling, in, multiple, biological, contexts])]). relacion([sujeto(['The', ubiquitous, role, of, microRNAs, '(', 'miRNAs)', in, a, number, of, pathological, processes]), verbo([has]), complemento([suggested, that, they, could, act, as, potential, drug, targets])]). relacion([sujeto(['RNA-binding', small, molecules, offer, an, attractive, means, for]), verbo([modulating]), complemento([miRNA, function])]). relacion([sujeto(['The', availability, of, bioassay, data, sets, for, a, variety, of, biological, assays, and, molecules, in, public, domain]), verbo([provides]), complemento([a, new, opportunity, toward, utilizing, them, to, create, models, and, further, utilize, them, for, in, silico, virtual, screening, approaches, to, prioritize, or, assign, potential, functions, for, small, molecules])]). relacion([sujeto(['Here,', we, describe, a, computational, strategy, based, on, machine, learning, for, creation, of, predictive, models, from, 'high-throughput', biological, screens, for, virtual, screening, of, small, molecules, with, the, potential, to]), verbo([inhibit]), complemento([microRNAs])]). relacion([sujeto(['With', the, number, of, stem, 'cell-based', therapies, emerging, on, the, 'increase,', the, need, for, novel, and, efficient, delivery, technologies, to, enable, therapies, to, remain, in, damaged, tissue, and, exert, their, therapeutic, benefit, for, extended, 'periods,']), verbo([has]), complemento([become, a, key, requirement, for, their, translation])]). relacion([sujeto(['Hydrogels,', and, in, 'particular,', thermoresponsive, 'hydrogels,']), verbo([have]), complemento([the, potential, to, act, as, such, delivery, systems])]). relacion([sujeto(['Thermoresponsive', 'hydrogels,', which, are, polymer, solutions, that, transform, into, a, gel, upon, a, temperature, 'increase,']), verbo([have]), complemento([a, number, of, applications, in, the, biomedical, field, due, to, their, tendency, to, maintain, a, liquid, state, at, room, 'temperature,', thereby, enabling, minimally, invasive, administration, and, a, subsequent, ability, to, form, a, robust, gel, upon, heating, to, physiological, temperature])]). relacion([sujeto(['However,', various, hurdles, must, be, overcome, to]), verbo([increase]), complemento([the, clinical, translation, of, hydrogels, as, a, stem, cell, delivery, 'system,', with, barriers, including, their, low, tensile, strength, and, their, inadequate, support, of, cell, viability, and, attachment])]). relacion([sujeto(['We', demonstrate, that, human, mesenchymal, stem, cells, '(', 'hMSCs)', encapsulated, within, the, gel, remained, viable, and, showed, raised, levels, of, dsDNA, at]), verbo([increasing]), complemento([time, 'points,', an, indication, of, cell, proliferation])]). relacion([sujeto([force]), verbo([required]), complemento([for, delivery, of, the, polymer, solution, through, devices, such, as, a, 'syringe,', needle, or, catheter])]). relacion([sujeto(['An', engineer, who, becomes, an, educator, in, a, school, of, software, engineering]), verbo([has]), complemento([the, mission, to, teach, how, to, design, and, construct, software, 'systems,', therein, applying, his, or, her, knowledge, and, expertise])]). relacion([sujeto(['However,', due, to, their, engineering, 'background,', engineers, may, forget, that, educating, a, person, is, not, the, same, as, designing, a, 'machine,', since, a, machine]), verbo([has]), complemento([a, 'well-defined', 'goal,', whilst, a, person, is, capable, to, 'self-propose', his, or, her, own, objectives])]). relacion([sujeto(['However,', the, 'dis-analogy', between, educating, students, and, programming, robots, may]), verbo([have]), complemento([a, particular, appeal, to, software, engineers, and, computer, scientists])]). relacion([sujeto(['We', think, the, consideration, of, three, different, stages, in, the, educational, process, may, be, useful, to, engineers, when, they]), verbo([act]), complemento([as, educators])]). relacion([sujeto(['The']), verbo([increasing]), complemento([demand, which, requires, ascertaining, the, legal, age, of, undocumented, individuals, who, reach, the, various, countries, of, the, 'European', 'Community', means, that, new, lines, of, research, must, be, developed, which, help, respond, to, questions, posed, by, the, 'Justice', 'Administration'])]). relacion([sujeto(['For', this, 'reason,', this, study]), verbo([has]), complemento([been, designed, on, the, basis, of, fusion, times, of, the, proximal, humeral, epiphysis])]). relacion([sujeto(['Moreover,', the, ultrasound, scan]), verbo([has]), complemento([been, used, as, the, diagnostic, method])]). relacion([sujeto(['Many', sesquiterpenes, are, volatile, compounds, and, it]), verbo([act]), complemento([as, chemical, messenger, in, plant, 'signalling,', particularly, in, the, defense, mechanism, against, biotic, and, abiotic, stresses])]). relacion([sujeto(['Panax', ginseng, 'Meyer', is, important, medicinal, herbs, with, various]), verbo([reported]), complemento([pharmacological, efficacies, in, which, its, triterpenoid, 'saponins,', called, 'ginsenosides,', were, mostly, studied])]). relacion([sujeto(['However,', there]), verbo([have]), complemento([been, few, studies, on, volatile, sesquiterpenes, compounds, regulation, on, 'P'])]). relacion([sujeto(['qRT-PCR', and, 'GC-MS', analysis, showed, that, two, 'elicitors-', salicylic, acid, '(', 'SA)', and, methyl, jasmonate, '(', 'MeJA)']), verbo([triggered]), complemento(['PgSTS', expression, at, different, time, points, and, significantly, induced, 'mono-,', sesquiterpene, yield])]). relacion([sujeto(['Overexpression', of, 'PgSTS', in, 'Arabidopsis', also]), verbo([induced]), complemento([high, terpene, content, and, conferred, tolerance, against, 'Pseudomonas', syringae, pv])]). relacion([sujeto(['These', results]), verbo([suggested]), complemento([that, 'PgSTS', transcripts, are, involved, in, terpenoid, biosynthesis, in, response, to, environmental, stress, mediated, by, 'MeJA', and, 'SA', 'elicitors;', 'thus,', generate, tolerance, against, pathogen, attack])]). relacion([sujeto(['In', 'plants,', various, 'phloem-mobile', macromolecules, including, noncoding, 'RNAs,', mRNAs, and, proteins, are]), verbo([suggested]), complemento([to, act, as, important, 'long-distance', signals, in, regulating, crucial, physiological, and, morphological, transition, processes, such, as, 'flowering,', plant, growth, and, stress, responses])]). relacion([sujeto(['Given', recent, advances, in, 'high-throughput', sequencing, 'technologies,', numerous, mobile, macromolecules]), verbo([have]), complemento([been, identified, in, diverse, plant, species, from, different, plant, families])]). relacion([sujeto(['To', facilitate, study, of, the, mobile, signaling, 'macromolecules,', we, compiled, the, 'PlaMoM', '(', 'Plant', 'Mobile', 'Macromolecules)', 'database,', a, resource, that]), verbo([provides]), complemento([convenient, and, interactive, search, tools, allowing, users, to, 'retrieve,', to, analyze, and, also, to, predict, mobile, 'RNAs/proteins'])]). relacion([sujeto(['Furthermore,', 'PlaMoM']), verbo([provides]), complemento([a, 'built-in', tool, to, identify, potential, 'RNA', mobility, signals, such, as, 'tRNA-like', structures])]). relacion([sujeto(['The', 'Tobacco', 'Control', 'Act']), verbo([requires]), complemento([public, disclosure, of, information, about, toxic, constituents, in, cigarette, smoke])]). relacion([sujeto(['Constituents', most, likely, to, discourage, respondents, from, wanting, to, smoke, were, 'ammonia,', 'arsenic,', 'formaldehyde,', hydrogen, 'cyanide,']), verbo([lead]), complemento([and, uranium])]). relacion([sujeto(['Respondents', more, often]), verbo([reported]), complemento([being, discouraged, by, constituents, that, they, had, heard, are, in, cigarette, smoke, '(', all, 'p<0'])]). relacion([sujeto(['Constituents', that, may, most, discourage, cigarette, smoking]), verbo([have]), complemento([familiar, 'names,', like, arsenic, and, formaldehyde, and, do, not, start, with, a, number, or, end, in, 'ene/ine'])]). relacion([sujeto(['How', 'Prp43', is]), verbo([regulated]), complemento([by, its, cofactors, to, discard, selectively, only, 'intron-lariat', spliceosomes, '(', 'ILS)', and, defective, spliceosomes, and, to, prevent, disassembly, of, earlier, and, properly, 'assembled/wild-type', spliceosomes, remains, unclear])]). relacion([sujeto(['First,', we, show, that, 'Ntr1\'s', 'G-patch', motif, '(', 'Ntr1GP)', can, be, replaced, by, the, 'GP', motif, of, 'Pfa1/Sqs1,', a, 'Prp43\'s', cofactor, in, ribosome, 'biogenesis,', demonstrating, that, the, specific, function, of, 'Ntr1GP', is, to]), verbo([activate]), complemento(['Prp43', for, spliceosome, disassembly, and, not, to, guide, 'Prp43', to, its, binding, site, in, the, spliceosome])]). relacion([sujeto(['Furthermore,', we, show, that, 'Ntr1\'s', 'C-terminal', domain, '(', 'CTD)', plays, a, safeguarding, role, by]), verbo([preventing]), complemento(['Prp43', from, disrupting, 'wild-type', spliceosomes, other, than, the, 'ILS'])]). relacion([sujeto(['In', both, type, of, 'spliceosomes,', 'Ntr1-CTD', impedes, 'Prp43-mediated', disassembly, while, the, 'Ntr1GP']), verbo([promotes]), complemento([disassembly])]). relacion([sujeto(['Our', data, indicate, that, 'Ntr1', and, 'Ntr2']), verbo([act]), complemento([as, '\'', 'doorkeepers\'', and, suggest, that, both, cofactors, inspect, the, 'RNP', structure, of, spliceosomal, complexes, thereby, targeting, suboptimal, spliceosomes, for, 'Prp43-mediated', disassembly])]). relacion([sujeto(['MYD88', 'mutations,', notably, the, recurrent, 'gain-of-function', 'L265P', 'variant,', are, a, distinguishing, feature, of, 'Activated', 'B-Cell', like, '(', 'ABC)', 'Diffuse', 'Large', 'B', 'Cell', 'Lymphoma', '(', 'DLBCL),']), verbo([leading]), complemento([to, constitutive, 'NFkB', pathway, activation])]). relacion([sujeto(['A', cohort, of, 361, 'DLBCL', cases, '(', 94, 'MYD88', mutant, and, 267, 'MYD88', 'wild-type)', was, submitted, to, next, generation, sequencing, '(', 'NGS)', focusing, on, 34, genes, in, order, to, analyze]), verbo([associated]), complemento([mutations, and, copy, number, 'variations,', as, well, as, gene, expression, 'profiling,', and, clinical, and, prognostic, analyses])]). relacion([sujeto(['Clustering', analysis, also, segregated, subgroups, according, to]), verbo([associated]), complemento([genetic, alterations, among, patients, with, the, same, 'MYD88', mutation])]). relacion([sujeto(['We', showed, that]), verbo([associated]), complemento(['CD79B', and, 'MYD88', 'L265P', mutations, act, synergistically, to, increase, 'NFkB', pathway, 'activation,', although, the, majority, of, 'MYD88', 'L265P', mutant, cases, harbor, downstream, 'NFkB', 'alterations,', which, can, predict, 'BTK', inhibitor, resistance])]). relacion([sujeto(['Finally,', although, the, 'MYD88', 'L265P', variant, was, not, an, independent, prognostic, factor, in, 'ABC', 'DLBCL,']), verbo([associated]), complemento(['CD79B', mutations, significantly, improved, the, survival, of, 'MYD88', 'L265P', mutant, 'ABC', 'DLBCL', in, our, cohort])]). relacion([sujeto(['This', study, highlights, the, relative, heterogeneity, of, 'MYD88', mutant, 'DLBCBL,', adding, to, the, 'field\'s', knowledge, of, the, theranostic, importance, of, 'MYD88', 'mutations,', but, also, of]), verbo([associated]), complemento(['alterations,', emphasizing, the, usefulness, of, genomic, profiling, to, best, stratify, patients, for, targeted, therapy])]). relacion([sujeto(['The', modulation, exerted, by, glucocorticoids, in, physiological, responses, to, stressors, is, essential, for]), verbo([maintaining]), complemento(['short-term', homeostasis])]). relacion([sujeto(['However,', highly, frequent, 'and/or', prolonged, activation, of, the, 'hypothalamic-pituitary-adrenal/interrenal', axis, may]), verbo([inhibit]), complemento([processes, that, are, important, to, 'long-term', fitness, and, 'health,', including, reproduction, and, immunocompetence])]). relacion([sujeto(['ACTH']), verbo([increased]), complemento(['CORT', levels, whilst, decreasing, 'T', and, 'MEL', levels, at, 1, h, 'post-treatment'])]). relacion([sujeto(['ACTH', treatment, did, not, significantly]), verbo([modulate]), complemento([the, immune, measures, over, the, 'time-range', sampled])]). relacion([sujeto(['The', hormonal, changes, observed, in, response, to, 'ACTH', treatment]), verbo([suggest]), complemento([that, stressors, could, act, as, inhibitors, of, reproductive, 'activity,', as, well, as, differentially, modulating, melatonin, levels, at, different, 'time-points'])]). relacion([sujeto(['MitoNEET,', a, primary]), verbo([target]), complemento([of, type, 'II', diabetes, drug, 'pioglitazone,', has, an, essential, role, in, regulating, energy, 'metabolism,', iron, 'homeostasis,', and, production, of, reactive, oxygen, species, in, mitochondria])]). relacion([sujeto(['Here', we]), verbo([report]), complemento([that, the, reduced, flavin, nucleotides, can, rapidly, reduce, the, mitoNEET, '[', 2, 'Fe-2S]', clusters, under, anaerobic, or, aerobic, conditions])]). relacion([sujeto(['The', electron, paramagnetic, resonance, '(', 'EPR)', measurements, show, that, flavin, mononucleotide, '(', 'FMN),', but, not, flavin, adenine, dinucleotide, '(', 'FAD),']), verbo([has]), complemento([a, specific, interaction, with, mitoNEET])]). relacion([sujeto(['Molecular', docking, models, further]), verbo([reveal]), complemento([that, flavin, mononucleotide, binds, mitoNEET, at, the, region, between, the, 'N-terminal', transmembrane, 'α-helix', and, the, '[', 2, 'Fe-2S]', cluster, binding, domain])]). relacion([sujeto(['The', closest, distance, between, the, '[', 2, 'Fe-2S]', cluster, and, the]), verbo([bound]), complemento([flavin, mononucleotide, in, mitoNEET, is, about, 10, 'Å,', which, may, facilitate, rapid, electron, transfer, from, the, reduced, flavin, nucleotide, to, the, '[', 2, 'Fe-2S]', cluster, in, mitoNEET])]). relacion([sujeto(['The', results]), verbo([suggest]), complemento([that, flavin, nucleotides, may, act, as, electron, shuttles, to, reduce, the, mitoNEET, '[', 2, 'Fe-2S]', clusters, and, regulate, mitochondrial, functions, in, human, cells])]). relacion([sujeto(['Toxicological', studies, of, defined, chemical, mixtures, assist, human, health, risk, assessment, by, establishing, how, chemicals]), verbo([interact]), complemento([with, one, another, to, induce, an, effect])]). relacion([sujeto(['The', reviewed, studies, compare, observed, mixture, data, to, mathematical, mixture, model, predictions, based, on, dose, addition, or, response, addition, to, determine, how, the, individual, chemicals, in, a, mixture]), verbo([interact]), complemento(['(', e])]). relacion([sujeto(['Phthalate', mixtures, were, observed, to]), verbo([act]), complemento([in, a, dose, additive, manner, based, on, the, relative, potency, of, the, individual, phthalates, to, suppress, fetal, testosterone, production])]). relacion([sujeto(['Similar', dose, additive, effects]), verbo([have]), complemento([been, reported, for, mixtures, of, phthalates, with, antiandrogenic, pesticides, of, differing, mechanisms, of, action])]). relacion([sujeto(['We', previously, demonstrated, the, presence, of, sonic, hedgehog, '(', 'Shh)', in, nasal, mucus, in, normal, subjects, and, in, patients, with, smell]), verbo([loss]), complemento(['(', 'hyposmia)'])]). relacion([sujeto(['Nasal', mucus, 'Shh', levels, were]), verbo([found]), complemento([significantly, diminished, in, untreated, hyposmic, patients, of, multiple, etiologies])]). relacion([sujeto(['Since', treatment, with, oral, theophylline]), verbo([has]), complemento([been, previously, associated, with, improvement, in, smell, function, we, wished, to, study, if, such, treatment, increased, nasal, mucus, 'Shh', as, well, as, improved, smell, function, in, patients, with, hyposmia])]). relacion([sujeto(['There', was, 'consistent,', significant, improvement, in, subjective, responses, in, 'smell,', taste, and, flavor, perception, and, in, olfactometry]), verbo([associated]), complemento([with, increased, nasal, mucus, 'Shh', and, serum, theophylline, after, theophylline, treatment])]). relacion([sujeto(['Results', are, consistent, with, a, successful, role, for, theophylline, in, improvement, of, smell, function, in, hyposmic, patients, of, multiple, etiologies]), verbo([associated]), complemento([with, increased, nasal, mucus, 'Shh', which, can, act, as, a, biochemical, marker, for, smell, function])]). relacion([sujeto(['In', the, 'Netherlands', in, 2006, a, major, health, care, reform, was, 'introduced,', aimed, at, reinforcing]), verbo([regulated]), complemento([competition, in, the, health, care, sector])]). relacion([sujeto(['Health', insurers, were]), verbo([provided]), complemento([with, strong, incentives, to, compete, and, more, room, to, negotiate, and, selectively, contract, with, health, care, providers])]). relacion([sujeto(['They']), verbo([have]), complemento([been, very, successful, in, mobilizing, public, support, against, unfavorable, contracting, practices, of, health, insurers, and, enforcement, of, the, competition, act])]). relacion([sujeto(['Due', to, ongoing, horizontal, 'consolidation,', hospital, markets, in, the, 'Netherlands']), verbo([have]), complemento([become, highly, concentrated])]). relacion([sujeto(['Despite', the, highly, concentrated, health, insurance, 'market,', it, is, unclear, whether, insurers, will]), verbo([have]), complemento([sufficient, countervailing, buyer, power, 'vis-à-vis', 'GPs', and, hospitals, to, effectively, fulfill, their, role, as, prudent, buyer, of, 'care,', as, envisioned, in, the, reform])]). relacion([sujeto(['To']), verbo([prevent]), complemento([further, consolidation, and, anticompetitive, 'coordination,', strict, enforcement, of, competition, policy, is, crucially, important, for, safeguarding, the, potential, for, effective, 'insurer-provider', negotiations, about, quality, and, price])]). relacion([sujeto([miRNAs, can]), verbo([act]), complemento([as, tumour, suppressors, or, 'oncogenes,', and, aberrant, expression, of, miRNAs, has, been, reported, in, several, human, cancers, and, has, been, associated, with, cancer, initiation, and, progression])]). relacion([sujeto(['Recent', evidence]), verbo([suggests]), complemento([that, miRNAs, play, a, major, role, in, thyroid, carcinogenesis])]). relacion([sujeto(['In', 'Germany,', psychotherapeutic, care, of, adolescent, refugees, is]), verbo([provided]), complemento([by, specialized, treatment, centers, and, 'Child', and, 'Adolescent', psychiatries, with, specialized, 'consultation-hours', for, refugees])]). relacion([sujeto(['Many', therapists]), verbo([have]), complemento([reservations, and, uncertainties, regarding, an, appropriate, therapy, for, refugees, due, to, a, lack, of, experience])]). relacion([sujeto(['This', means, that, only, a, fraction, of, the, young, refugees, with, 'trauma-related', disorders]), verbo([find]), complemento([an, ambulatory, therapist])]). relacion([sujeto(['Significance', 'Redox', signaling, is, one, of, the, key, elements]), verbo([involved]), complemento([in, cardiovascular, diseases])]). relacion([sujeto(['Interestingly,', 'Nrf2', and, 'Trx-1', can]), verbo([act]), complemento([together, as, well, as, independently, of, each, other, in, protection, against, atherosclerosis, and, ischemia, and, reperfusion, injury])]). relacion([sujeto(['Critical', 'Issues', 'In', 'principle,', pharmacological, activation, of, a, transcription, factor, like, 'Nrf2', can, be, 'dangerous,', since, a, transcription, regulator]), verbo([has]), complemento([multiple, targets, and, the, pleiotropic, effects, of, such, activation, should, not, be, ignored])]). relacion([sujeto(['Future', 'Directions', 'Therefore,', length, of, treatment, with, 'Nrf2', activators, 'and/or', 'Trx-1']), verbo([has]), complemento([first, to, be, studied, in, more, detail, in, cardiovascular, disorders])]). relacion([sujeto([of, 'Chemical', 'Substances', '(', 'ARECS)\'', or, the, new, '\'', 'Biocidal', 'Product', 'Act\'', must, not, only, address, the, blind, areas, in, the, management, system, for, chemical, and, product, 'safety,', but, also]), verbo([prevent]), complemento([a, second, 'HDD'])]). relacion([sujeto(['To']), verbo([prevent]), complemento([another, 'HDD,', an, integrated, 'registration,', 'evaluation,', and, management, system, for, chemicals, and, consumer, products, must, be, incorporated, into, the, '\'', 'ARECS\'', as, an, essential, part, for, chemical, safety, in, consumer, products])]). relacion([sujeto(['Like', everyone, who, 'cares,', we, search, for, an, answer, to, the, reason, why, a, fellow, human, could, carry, out, such, a, senseless]), verbo([act]), complemento([as, the, 'Soho', bombing])]). relacion([sujeto(['We', are, horrified, 'because,', as, 'Paul', 'Boateng,', the, home, minister, 'said,', we]), verbo([have]), complemento([a, right, to, be, different, in, a, pluralistic, society])]). relacion([sujeto(['MINISTERS', 'SHOULD', urge, the, 'European', 'Union', to, overturn, a, decision, that, will, allow, '\'', 'underqualified\'', 'Polish', nurses, the, automatic, right, to, practise, in, the, 'UK,', nursing, organisations]), verbo([have]), complemento([said])]). relacion([sujeto(['So,', 'it\'s', 'official,', even, unto, the, wife, of, the, prime, minister, -, a, lifestyle, guru]), verbo([has]), complemento([become, an, essential, prerequisite, to, happiness])]). relacion([sujeto(['Having', someone, in, your, life, to, help, you, look, 'right,', speak, right, and]), verbo([act]), complemento([right, is, now, as, necessary, as, that, not, so, subtly, hidden, designer, label, or, the, particular, holiday, destination, that, is, '\'', 'in\'', this, year])]). relacion([sujeto(['In', response, to, replication, stress, cells]), verbo([activate]), complemento([the, 'intra-S', 'checkpoint,', induce, 'DNA', repair, 'pathways,', increase, nucleotide, 'levels,', and, inhibit, origin, firing])]). relacion([sujeto(['Here,', we]), verbo([report]), complemento([that, 'Rrm3', associates, with, a, subset, of, replication, origins, and, controls, 'DNA', synthesis, during, replication, stress])]). relacion([sujeto(['The', 'N-terminal', domain]), verbo([required]), complemento([for, control, of, 'DNA', synthesis, maps, to, residues, 186, -, 212, that, are, also, critical, for, binding, 'Orc5', of, the, origin, recognition, complex])]). relacion([sujeto(['Deletion', of, this, domain, is, lethal, to, cells, lacking, the, replication, checkpoint, mediator, 'Mrc1', and]), verbo([leads]), complemento([to, mutations, upon, exposure, to, the, replication, stressor, hydroxyurea])]). relacion([sujeto(['Using', quantitative, mass, spectrometry, and, genetic, 'analyses,', we]), verbo([find]), complemento([that, the, homologous, recombination, factor, 'Rdh54', and, 'Rad5-dependent', 'error-free', 'DNA', damage, bypass, act, as, independent, mechanisms, on, 'DNA', lesions, that, arise, when, 'Rrm3', catalytic, activity, is, disrupted, whereas, these, mechanisms, are, dispensable, for, 'DNA', damage, tolerance, when, the, replication, function, is, 'disrupted,', indicating, that, the, 'DNA', lesions, generated, by, the, loss, of, each, 'Rrm3', function, are, distinct])]). relacion([sujeto(['Although', both, lesion, types]), verbo([activate]), complemento([the, 'DNA-damage', 'checkpoint,', we, find, that, the, resultant, increase, in, nucleotide, levels, is, not, sufficient, for, continued, 'DNA', synthesis, under, replication, stress])]). relacion([sujeto(['Together,', our, findings]), verbo([suggest]), complemento([a, role, of, 'Rrm3,', via, its, 'Orc5-binding', 'domain,', in, restricting, 'DNA', synthesis, that, is, genetically, and, physically, separable, from, its, established, catalytic, role, in, facilitating, fork, progression, through, replication, blocks])]). relacion([sujeto(['The', 'Americans', 'With', 'Disabilities', 'Act']), verbo([requires]), complemento([that, nursing, programs, not, discriminate, against, students, with, disabilities])]). relacion([sujeto(['The', 'Mental', 'Capacity', 'Act', '(', 'MCA)', is, statutory, legislation, introduced, in, 2007, to, protect, and, empower, people, to, make, decisions, for, themselves, and, those, who, were, deemed, as, unable, to, make, choices, would]), verbo([have]), complemento([decisions, made, on, their, 'behalf,', often, by, health, professionals])]). relacion([sujeto(['Yet', a, scrutiny]), verbo([report]), complemento([by, the, 'House', of, 'Lords', concluded, this, legislation, was, 'under-used', with, a, lack, of, knowledge, among, professionals, regarding, applying, the, legislation, in, practice])]). relacion([sujeto(['While', findings]), verbo([suggest]), complemento([clear, examples, of, 'self-appraised', confidence, and, excewllent, patient, 'care,', there, is, also, scope, for, development, regarding, the, knowledge, and, utilisation, of, the, 'MCA', in, the, clinical, practice, of, community, nurses])]). relacion([sujeto(['The', pristine, graphene, sheets, did, not, disrupt, the, packing, of, the, liquid, crystals, while, being, in, sufficiently, intimate, contact, to]), verbo([provide]), complemento([localized, heating, and, induce, phase, transitions])]). relacion([sujeto(['The', phase, progressions]), verbo([induced]), complemento([through, heating, using, 'NIR', irradiation, of, the, entrained, graphene, particles, within, the, bulk, liquid, crystal, were, studied, using, 'SAXS', and, confirmed, using, polarized, optical, microscopy])]). relacion([sujeto(['Furthermore,', while, such, autophagosomes, can, fuse, with, 'lysosomes,', their, degradation, is, 'delayed,', and, this, is]), verbo([associated]), complemento([with, delayed, destruction, of, the, inner, autophagosomal, double, 'membrane,', highlighting, a, new, role, for, proteins, thought, to, act, exclusively, in, the, formation, of, autophagosomes, in, late, stages, of, the, autophagic, itinerary, within, autolysosomes])]). relacion([sujeto(['Ordering', a, genetic, test, is, a, complex, process]), verbo([involving]), complemento([consideration, of, many, basic, ethical, principles, including, 'autonomy,', 'beneficence,', and, 'nonmaleficence,', as, well, as, the, 'physician\'s', duty, to, act, in, the, 'patient\'s', best, interest])]). relacion([sujeto(['Physicians']), verbo([have]), complemento([many, choices, regarding, what, tests, to, 'order,', and, they, must, develop, the, knowledge, and, skills, to, best, discuss, genetic, testing, with, their, patients])]). relacion([sujeto(['Integration', of, core, ethical, principles, into, these, processes, will, permit, physicians, to, best, serve, their, patients, when, obtaining, informed, 'consent,', considering, advantages, and, harms, of, potential, 'results,', disclosing, those, 'results,', and]), verbo([providing]), complemento(['follow-up'])]). relacion([sujeto(['Generally,', under, 'Health', 'Insurance', 'Portability', and, 'Accountability', 'Act,', personal, representatives]), verbo([have]), complemento([the, same, authority, to, receive, information, that, patients, would, otherwise, have])]). relacion([sujeto(['Persons']), verbo([involved]), complemento([in, the, 'patient\'s', care, also, may, be, given, information, relevant, to, the, episode, of, care, unless, the, patient, objects])]). relacion([sujeto(['ICUs', should, develop, policies, for, handling, the, issues, we, identify, about, such, information, 'sharing,', including, policies, for]), verbo([responding]), complemento([to, telephone, inquiries, and, methods, for, giving, patients, the, opportunity, to, object, to, sharing, information, with, individuals, involved, in, their, care])]). relacion([sujeto(['Indirect', evidence]), verbo([suggests]), complemento([that, the, uptake, and, effectiveness, of, cCBT, can, be, increased, if, facilitated, by, 'telephone,', but, this, is, not, routinely, offered, in, the, 'NHS'])]). relacion([sujeto(['Participants', were]), verbo([recruited]), complemento([from, 'GP', practices, in, 'Bristol,', 'Manchester,', 'Sheffield,', 'Hull', and, the, 'north-east', of, 'England'])]). relacion([sujeto(['Potential', participants, were, eligible, to]), verbo([participate]), complemento([in, the, trial, if, they, were, adults, with, depression, scoring, '≥', 10, on, the, 'Patient', 'Health', 'Questionnaire-9', '(', 'PHQ-9)'])]). relacion([sujeto(['There', were]), verbo([gains]), complemento([in, 'quality-adjusted', 'life-years', at, reduced, cost, when, telephone, facilitation, was, added, to, 'MoodGYM'])]). relacion([sujeto(['Participants\'', depression, was, assessed, with, the, 'PHQ-9,', cCBT, use, was, quite, low, and, there, was, a, slightly, greater, than, anticipated]), verbo([loss]), complemento([to, 'follow-up'])]). relacion([sujeto(['Increasing', evidence]), verbo([suggests]), complemento([that, these, enzymes, exert, their, effect, rather, through, molecular, recognition, of, acetylated, proteins, and, recruiting, other, proteins, like, 'HDAC3', to, the, desired, target, location])]). relacion([sujeto(['Accordingly,', class, 'IIa', 'HDACs', like, bromodomains]), verbo([have]), complemento([been, suggested, to, act, as, &, 'quot;Readers"', of, acetyl, 'marks,', whereas, enzymatically, active, 'HDACs', from, class, 'I', or, 'IIb', are, called, &, 'quot;Erasers"', to, highlight, their, capability, to, remove, acetyl, groups, from, acetylated, histones, or, other, proteins])]). relacion([sujeto(['Small', molecule, ligands, of, class, 'IIa', histone, deacetylases, '(', 'HDACs)', gained, tremendous, attention, during, the, last, decade, and, were]), verbo([suggested]), complemento([as, pharmaceutical, target, in, several, indication, areas, such, as, 'cancer,', 'Huntington\'s', disease, or, muscular, atrophy])]). relacion([sujeto(['Up', to, now, only, enzyme, activity, assays, with, artificial, chemically]), verbo([activated]), complemento([trifluoroacetylated, substrates, are, in, use, for, the, identification, and, characterization, of, new, active, compounds, against, class, 'IIa', 'HDACs'])]). relacion([sujeto(['Here,', we, describe, the, first]), verbo([binding]), complemento([assay, for, this, class, of, 'HDAC', enzymes, with, simple, 'mix-and-measure', procedure, and, extraordinary, robust, fluorescence, lifetime, readout, based, on, '[', 1, ',', 3, ']', 'dioxolo[4,5-f]benzodioxole-based', ligand, probes])]). relacion([sujeto(['While', noise, always, tends, to, synchronize, the, phase, 'oscillators,', the, repulsive, coupling, can]), verbo([act]), complemento([against, 'synchrony,', and, we, focus, on, this, nontrivial, situation])]). relacion([sujeto(['For', oscillators, with, a, distribution, of, natural, 'frequencies,', we]), verbo([report]), complemento([on, a, 'counter-intuitive', effect, of, dispersion, '(', instead, of, usual, 'convergence)', of, the, oscillators, frequencies, at, 'synchrony;', the, latter, effect, disappears, if, noise, vanishes])]). relacion([sujeto(['We']), verbo([report]), complemento([the, unprecedented, 'Lapita', exploitation, and, subsequent, extinction, of, large, megafauna, tortoises, '(', ?, 'Meiolania', 'damelipi)', on, tropical, islands, during, the, late, 'Holocene', over, a, 281, ',', 0, 'km(2)', region, of, the, southwest, 'Pacific', spanning, from, the, 'Vanuatu', archipelago, to, 'Viti', 'Levu', in, 'Fiji'])]). relacion([sujeto(['Zooarchaeological', analyses]), verbo([have]), complemento([identified, seven, early, archaeological, sites, with, the, remains, of, this, distinctive, hornless, 'tortoise,', unlike, the, 'Gondwanan', horned, meiolaniid, radiation, to, the, southwest])]). relacion([sujeto(['These', large, tortoise, radiations, in, the, 'Pacific', may]), verbo([have]), complemento([contributed, to, the, rapid, dispersal, of, early, mobile, 'Neolithic', hunters, throughout, southwest, 'Melanesia', and, on, to, western, 'Polynesia'])]). relacion([sujeto(['Subsequent', rapid, extinctions, of, these, terrestrial, herbivorous, megafauna, are, likely, to]), verbo([have]), complemento([led, to, significant, changes, in, ecosystems, that, help, explain, changes, in, current, archaeological, patterns, from, 'Post-Lapita', contexts, in, the, region])]). relacion([sujeto(['We', study, the]), verbo([enhanced]), complemento([dewetting, of, ultrathin, 'Polystyrene', '(', 'PS)/Poly', '(', methyl, 'methacrylate)', '(', 'PMMA)', blend, films, in, a, mixed, 'solution,', and, reveal, the, dewetting, can, act, as, a, simple, and, effective, method, to, fabricate, 'large-area', 'surface-enhanced', 'Raman', scattering, '(', 'SERS)', substrate])]). relacion([sujeto(['The']), verbo([enhanced]), complemento([dewetting, of, polymer, blend, films, broadens, the, application, of, dewetting, of, polymer, 'films,', especially, in, the, 'nanotechnology,', and, may, open, a, new, approach, for, the, fabrication, of, 'large-area', 'SERS', substrate, to, promote, the, application, of, 'SERS', substrate, in, the, rapid, sensitive, detection, of, trace, molecules])]). relacion([sujeto(['In', 'addition,', molecular, docking, revealed, that, 'benzo[h]quinolines', can, correctly, dock, into, the, hydrophobic, pocket, of, the]), verbo([targets]), complemento([receptor, protein, aromatase, and, 'CDK2,', while, their, 'bioavailability/drug-likeness', was, predicted, to, be, acceptable, but, requires, future, optimization])]). relacion([sujeto(['These', findings]), verbo([reveal]), complemento([that, 'benzo[h]quinolines', act, as, 'anti-cancer', agents, by, inducing, oxidative, 'stress-mediated', 'DNA', damage])]). relacion([sujeto(['Physical', exercise, can, reduce, adverse, conditions, during, 'aging,', while, both, exercise, and, aging]), verbo([act]), complemento([as, metabolism, modifiers])]). relacion([sujeto(['Fecal', samples, and, cecal, extracts, were, analyzed, by]), verbo([targeted]), complemento([and, untargeted, metabolic, profiling, methods, '(', 'GC-MS', and, 'LC-MS/MS)'])]). relacion([sujeto(['The', present, generation, of, women, of, childbearing, age, more, frequently, suffer, from, 'overweight,', 'obesity,', initial, as, well, as, fully, established, metabolic, 'syndrome,', which, together, with, postponing, motherhood, until, the, third, decade, in, life, plays, an, important, role, in, the]), verbo([increasing]), complemento([incidence, of, gestational, diabetes, '(', 'GDM)', that, currently, affects, about, 1, /, 5, of, pregnant, women])]). relacion([sujeto(['It', is, a, positive, sign, that, the, 'Czech', professional, associations]), verbo([have]), complemento([adopted, new, international, criteria, for, diagnosing, 'GDM', 'which,', as, opposed, to, those, valid, 'earlier,', better, reflect, the, risk, of, 'pregnancy-related', and, perinatal, complications])]). relacion([sujeto(['The', care, for, gestational, patients, with, diabetes, at, a, low, risk, '(', due, to, satisfactory, glycemic, control, through, a, diet, or, small, pharmacotherapeutic, 'doses,', with, an, eutrophic, fetus, and, without]), verbo([associated]), complemento(['complications)', is, provided, by, an, outpatient, gynecologist, and, a, diabetes, 'specialist,', they, can, give, birth, in, standard, maternity, hospitals])]). relacion([sujeto(['The', base, for, therapy, is, formed, by, 'regimen-related', 'measures:', the, therapeutic, diet, and]), verbo([increased]), complemento([physical, activity])]). relacion([sujeto(['The', best, results, of, the, dietary, therapy, are, achieved, with, foods, low, on, glycemic, index, and, glycemic, load, that, can, also]), verbo([act]), complemento([as, efficient, prevention, of, 'GDM', and, subsequent, development, of, 'T2DM'])]). relacion([sujeto(['A', small, number, of, cases]), verbo([require]), complemento([adding, of, pharmacological, 'therapy:', insulin, and, newly, also, metformin])]). relacion([sujeto([due, to, obesity, or, a, great, weight, 'gain,', may]), verbo([lead]), complemento([to, macrosomia, and, epigenetic, changes])]). relacion([sujeto(['Polyamines', '(', 'PAs)', and, nitric, oxide, '(', 'NO)', are, vital, signals, in]), verbo([modulating]), complemento([plant, response, to, abiotic, stress])]). relacion([sujeto(['Spd']), verbo([increased]), complemento(['NO', release, via, the, nitric, oxide, synthase, '(', 'NOS)-like', and, nitrate, reductase, '(', 'NR)', enzymatic, pathways, in, the, 'seedlings,', whereas, 'Put', had, no, such, effect])]). relacion([sujeto(['Moreover,', 'H2O2', might]), verbo([act]), complemento([as, an, upstream, signal, to, stimulate, 'NO', production])]). relacion([sujeto(['Both', exogenous, 'NO', donor, '(', sodium, nitroprusside, '(', 'SNP))', and, 'Spd']), verbo([enhanced]), complemento([chilling, tolerance, in, 'tomato,', thereby, protecting, the, photosynthetic, system, from, damage])]). relacion([sujeto(['Compared', to, chilling, treatment, 'alone,', 'Spd']), verbo([enhanced]), complemento([the, gene, expressions, of, superoxide, dismutase, '(', 'SOD),', peroxidase, '(', 'POD),', catalase, '(', 'CAT),', and, ascorbate, peroxidase, '(', 'APX),', and, their, enzyme, activities, in, tomato, leaves])]). relacion([sujeto(['However,', a, scavenger, or, inhibitor, of, 'NO', abolished, 'Spd-induced', chilling, tolerance, and, blocked, the]), verbo([increased]), complemento([expression, and, activity, due, to, 'Spd', of, these, antioxidant, enzymes, in, tomato, leaves, under, chilling, stress])]). relacion([sujeto(['The', results, showed, that, 'NO']), verbo([induced]), complemento([by, 'Spd', plays, a, crucial, role, in, 'tomato\'s', response, to, chilling, stress])]). relacion([sujeto(['To', explain, the, effects, of, peptides, of, intermolecular, 'processes,', the, hypothesis, that, a, synactonal, mechanism, underlies, the, action, of, regulatory, 'peptides,', exemplified, by, the, heptapeptide, 'Semax,']), verbo([has]), complemento([been, proposed])]). relacion([sujeto(['These', peptides]), verbo([have]), complemento([their, own, binding, sites, with, similar, although, differing, characteristics])]). relacion([sujeto(['Together', with, 'Semax,', they, constitute, a, single, complex, of, bioregulators]), verbo([acting]), complemento([in, a, certain, sequence, and, in, 'interaction,', 'ie,', synacton])]). relacion([sujeto(['Specific', interactions, between, some, 'tritium-labeled', peptides, '(', basic, constituents, of, the, 'Semax', 'synacton)', and, plasma, membranes, of, neurons]), verbo([have]), complemento([been, characterized])]). relacion([sujeto(['Only', a, few, peptides, of, the, 'Semax', synacton, showed, competitive, activity, for, the, 'Semax']), verbo([binding]), complemento([sites])]). relacion([sujeto(['So', the, intermolecular, interactions, of, these, peptides, with, plasma, membranes, of, neuronal, brain]), verbo([targets]), complemento([are, probably, not, limited, by, specific, binding, at, orthosteric, sites])]). relacion([sujeto(['The', effect, of, peptides, that]), verbo([act]), complemento([in, the, synacton, considerably, extends, the, regulatory, potential, of, the, initial, molecule])]). relacion([sujeto(['The', case, here]), verbo([reported]), complemento([involves, a, schizophrenic, 19, -, 'year-old', girl, under, treatment, with, 'clotiapine,', which, was, well, tolerated, except, for, a, moderate, dry, mouth])]). relacion([sujeto(['The', woman, ingested, a, whole, sole, '(', 'Solea', 'solea),', which]), verbo([caused]), complemento([a, very, rapid, death, by, choking])]). relacion([sujeto(['At', 'autopsy,', the, sole, was, wedged, in, the, esophagus]), verbo([causing]), complemento([a, choking, ab, extrinseco])]). relacion([sujeto(['The', peculiarity, of, this, case, is, represented, by, two, 'factors:', one, is, the, choking, by, fish, and, the, second, was, the, adverse, affect]), verbo([caused]), complemento([by, 'clotiapine,', which, induced, a, condition, of, dry, mouth, making, the, act, of, swallowing, even, more, 'difficult,', thereby, contributing, to, a, very, rapid, mechanical, asphyxia, and, the, death, of, the, young, woman])]). relacion([sujeto(['Recent', studies]), verbo([have]), complemento([identified, 'Engrailed-2', '(', 'EN-2),', a, 'homeobox-containing', transcription, 'factor,', as, a, candidate, oncogene, in, prostate, cancer, '(', 'PC)'])]). relacion([sujeto(['Therapeutic']), verbo([targeting]), complemento([on, 'EN-2,', 'however,', is, limited, because, the, mechanism, underlying, 'EN-2', overexpression, in, prostatic, cancer, cells, is, unknown])]). relacion([sujeto(['miR-33a', overexpression]), verbo([suppresses]), complemento([prostate, cancer, cell, survival, and, metastasis])]). relacion([sujeto(['miR-33a', can, directly]), verbo([act]), complemento([on, 'EN-2', expression, by, binding, to, 3, '\'', 'UTR', of, its, mRNA])]). relacion([sujeto(['Also,', 'miR-33a', negatively]), verbo([regulated]), complemento(['EN-2', mRNA, and, protein, expression])]). relacion([sujeto(['The', pivotal, role, of, 'miR-33a', in]), verbo([inhibiting]), complemento([prostate, tumor, growth, was, confirmed, in, xenograft, models, of, prostate, cancer])]). relacion([sujeto(['Our', data]), verbo([suggest]), complemento([that, the, functional, interaction, of, 'miR-33a', and, 'EN-2', is, involved, in, tumorigenesis, of, prostate, cancer])]). relacion([sujeto(['Also', in, this, process, 'EN-2', serves, as, a, negative]), verbo([responder]), complemento([for, 'miR-33a'])]). relacion([sujeto(['Volitional', action, and, 'self-control-feelings', of]), verbo([acting]), complemento([according, to, 'one\'s', own, intentions, and, in, being, control, of, 'one\'s', own, 'actions-are', fundamental, aspects, of, human, conscious, experience])]). relacion([sujeto(['In', this, 'study,', we, manipulated, free, choice, decisions, to]), verbo([act]), complemento([or, withhold, an, action, by, subliminally, presenting, emotional, 'faces:', 'In', a, novel, version, of, the, 'Go/NoGo', 'paradigm,', participants, made, speeded, 'button-press', responses, to, 'Go', 'targets,', withheld, responses, to, 'NoGo', 'targets,', and, made, 'spontaneous,', free, choices, to, execute, or, withhold, the, response, for, 'Choice', targets])]). relacion([sujeto(['After', replicating, the, behavioural, results]), verbo([found]), complemento([in, 'Experiment', 1, ',', we, identified, a, 'frontal-midline', theta, 'component-associated', with, cognitive, control, 'processes-which', is, present, for, volitional, 'decisions,', and, is, modulated, by, subliminal, angry, faces])]). relacion([sujeto(['This']), verbo([suggests]), complemento([a, mechanism, whereby, subliminally, presented, &, 'quot;threat"', stimuli, affect, conscious, control, processes])]). relacion([sujeto(['In', 'summary,', nonconscious, perception, of, angry, faces]), verbo([increases]), complemento([choices, to, 'inhibit,', and, subliminal, influences, on, volitional, action, are, deep, seated, and, ecologically, embedded])]). relacion([sujeto(['Difficulties', in, the, supervisor, relationship, and, problematic, personal, and, professional, skills, often, become, the, focus, of]), verbo([targeted]), complemento([supervision, efforts, after, the, effects, of, deficits, '(', e])]). relacion([sujeto(['The', primary, purpose, of, this, paper, is, to]), verbo([provide]), complemento([guidance, to, the, 'supervisor\'s', effort, to, identify, and, address, barriers, to, successful, supervision, related, to, a, damaged, supervisory, relationship, and, persistent, interpersonal, and, professional, skills, of, the, supervisee])]). relacion([sujeto(['A', secondary, purpose, of, this, paper, is, to]), verbo([act]), complemento([as, a, general, call, to, supervisors, to, continually, and, thoughtfully, reflect, on, their, own, 'history,', 'repertoires,', and, 'behavior,', such, that, they, may, continue, professional, growth, as, supervisors])]). relacion([sujeto(['Rationale:', 'Current', 'first-line', treatments, for, 'stress-related', disorders, such, as, major, depressive, disorder, '(', 'MDD)']), verbo([act]), complemento([on, monoaminergic, systems, and, take, weeks, to, achieve, a, therapeutic, effect, with, poor, response, and, low, remission, rates])]). relacion([sujeto(['Recent', research]), verbo([has]), complemento([implicated, the, 'GABAergic', system, in, the, pathophysiology, of, 'depression,', including, deficits, in, interneurons, targeting, the, dendritic, compartment, of, cortical, pyramidal, cells])]). relacion([sujeto(['Objectives:', 'The', present, study, evaluates, whether, 'SH-053-2\'F-R-CH3', '(', denoted, &, 'quot;α5-PAM"),', a, positive, allosteric, modulator, selective, for, 'α5-subunit', containing, 'GABAA', receptors]), verbo([found]), complemento([predominantly, on, cortical, pyramidal, cell, 'dendrites,', has, 'anti-stress', effects])]). relacion([sujeto(['Results:', 'Acute', and, chronic, 'α5-PAM', treatments, produce, a, pattern, of]), verbo([decreased]), complemento(['stress-induced', behaviors, '(', denoted, as, &, 'quot;behavioral', 'emotionality")', across, various, tests, in, 'female,', but, not, in, male, mice])]). relacion([sujeto(['Behavioral', 'Z-scores', calculated, across, a, panel, of, tests, designed, to, best, model, the, range, and, heterogeneity, of, human, symptomatology, confirmed, that, acute, and, chronic, 'α5-PAM', treatments, consistently, produce, significant]), verbo([decreases]), complemento([in, behavioral, emotionality, in, several, independent, cohorts, of, females])]). relacion([sujeto(['In', mice, exposed, to, 'UCMS,', expression, of, the, 'Gabra5', gene, was]), verbo([increased]), complemento([in, the, frontal, cortex, after, acute, treatment, and, in, the, hippocampus, after, chronic, treatment, with, 'α5-PAM', in, females, 'only,', and, these, expression, changes, correlated, with, behavioral, emotionality])]). relacion([sujeto(['Conclusion:', 'We', showed, that, acute, and, chronic, positive, modulation, of, α5, 'subunit-containing', 'GABAA', receptors, elicit, 'anti-stress', effects, in, a, 'sex-dependent', 'manner,']), verbo([suggesting]), complemento([novel, therapeutic, modalities])]). relacion([sujeto(['A', 50, -, 'year-old', male, with, advanced, 'non-small-cell', lung, cancer, was, unable, to]), verbo([have]), complemento(['standard-of-care', molecular, testing, performed, at, diagnosis, as, a, result, of, inadequacy, of, the, available, tissue])]). relacion([sujeto(['A', subsequently, performed, commercial, liquid, tumor, biopsy, '(', 'Foundation', 'ACT(®))', revealed, an, epidermal, growth, factor, receptor, exon, 19, 'deletion,', but, due, to, the, progression, of, the, tumor, and, rapid, deterioration, in, the, 'patient\'s', performance, 'status,', a, meaningful, attempt, at, therapy, directed, to, this]), verbo([recognized]), complemento([therapeutic, target, was, not, possible])]). relacion([sujeto(['This', case]), verbo([provides]), complemento([important, support, for, the, relevance, of, liquid, tumor, biopsies, in, documenting, highly, clinically, relevant, molecular, 'targets,', particularly, in, the, setting, where, limited, solid, tumor, tissue, is, available, for, analysis])]). relacion([sujeto(['Second,', we, review, a, strategy, for, mitigating, imbalance]), verbo([associated]), complemento([with, vestibular, pathology, and, fostering, readaptation])]). relacion([sujeto(['In', discussing, the, first, strategy, '(', for, imbalance, 'assessment),', we, review, a, pilot, study, wherein, imbalance, was, elicited, '(', among, healthy, 'subjects)', via, an, adaptive, challenge, that]), verbo([caused]), complemento([a, 'temporary/reversible', disruption])]). relacion([sujeto(['The', surrogate, vestibular, deficit, was]), verbo([caused]), complemento([by, a, brief, period, of, 'movement-induced', adaptation, to, an, altered, '(', 'rotating)', gravitoinertial, frame, of, reference])]). relacion([sujeto(['This', elicited, adaptation, and]), verbo([caused]), complemento([imbalance, when, head, movements, were, made, after, reentry, into, the, normal, '(', 'non-rotating)', frame, of, reference])]). relacion([sujeto([',', a, prototype, tactile, sway, feedback, device, for, aiding, 'balance/recovery', after, disruptions]), verbo([caused]), complemento([by, vestibular, pathology])]). relacion([sujeto(['Thyroid', cancer, is, the, most, frequent, malignancies, of, the, endocrine, 'system,', and, it]), verbo([has]), complemento([became, the, fastest, growing, type, of, cancer, worldwide])]). relacion([sujeto(['Studies']), verbo([have]), complemento([found, that, some, certain, relationship, between, 'ARAP3', and, human, cancer])]). relacion([sujeto(['However,', the, role, of, 'ARAP3', in, thyroid, cancer]), verbo([has]), complemento([not, been, well, explained])]). relacion([sujeto(['Using', 'next-generation', sequence, and, bioinformatics, 'analysis,', we]), verbo([found]), complemento(['ARAP3', genes, may, play, an, important, role, in, thyroid, cancer])]). relacion([sujeto(['Downregulation', of, 'ARAP3', significantly]), verbo([suppressed]), complemento(['PTC', cell, lines, '(', 'TPC1,', 'BCPAP,', and, 'KTC-1),', cell, 'proliferation,', colony, 'formation,', 'migration,', and, invasion])]). relacion([sujeto(['This', study, indicated, that, 'ARAP3', genes]), verbo([have]), complemento([important, biological, implications, and, may, act, as, a, potentially, drugable, target, in, 'PTC'])]). relacion([sujeto(['The', 'Affordable', 'Care', 'Act']), verbo([requires]), complemento([state, 'Medicaid', programs, to, cover, substance, use, disorder, treatment, for, their, 'Medicaid', expansion, population, but, allows, states, to, decide, which, individual, services, are, reimbursable])]). relacion([sujeto(['To', examine, how, states]), verbo([have]), complemento([defined, substance, use, disorder, benefit, 'packages,', we, used, data, from, 2013, -, 14, that, we, collected, as, part, of, an, ongoing, nationwide, survey, of, state, 'Medicaid', programs])]). relacion([sujeto(['Many', states, did, not, cover, all, levels, of, care]), verbo([required]), complemento([for, effective, substance, use, disorder, treatment, or, medications, required, for, effective, opioid, use, disorder, treatment, as, defined, by, 'American', 'Society', of, 'Addiction', 'Medicine', 'criteria,', which, could, result, in, lack, of, access, to, needed, services, for, 'low-income', populations])]). relacion([sujeto(['This', study]), verbo([provides]), complemento([a, 'forward-thinking', assessment, of, the, factors, likely, to, affect, future, trends, in, dental, care, in, the, 'United', 'States'])]). relacion([sujeto(['Our', forecasts]), verbo([suggest]), complemento([that, the, medical, and, dental, insurance, reforms, instituted, under, the, 'Affordable', 'Care', 'Act', will, increase, rates, of, dental, care, use, and, the, number, of, dental, 'visits,', with, utilization, rates, reaching, 47, &, 'nbsp;percent', in, 2026, and, the, number, of, visits, reaching, 334, &, 'nbsp;million,', under, optimistic, assumptions, about, 'take-up', of, pediatric, dental, coverage])]). relacion([sujeto(['Our', forecasting, model, also, indicates, that, visits, for, preventive, dental, care, will]), verbo([increase]), complemento([in, the, 'future,', while, visits, for, dental, treatment, will, decline])]). relacion([sujeto(['Our', forecasts, can, be, used, to, infer, future, need, for, different, types, of, dental, care, providers, and, to]), verbo([provide]), complemento([policy, makers, with, the, information, needed, to, consider, the, expansion, of, mandates, for, dental, benefit, coverage, to, adult, populations, covered, by, 'Medicaid,', 'Medicare,', and, individual, and, 'small-group', plans, sold, on, health, insurance, exchanges])]). relacion([sujeto(['As', a, 'result,', even, with, the, recent, health, insurance, 'expansion,', many, 'Americans', face, financial, barriers, to, receiving, dental, care, that]), verbo([lead]), complemento([to, unmet, oral, health, needs])]). relacion([sujeto(['We']), verbo([found]), complemento([that, irrespective, of, 'age,', income, 'level,', and, type, of, 'insurance,', more, people, reported, financial, barriers, to, receiving, dental, 'care,', compared, to, any, other, type, of, health, care])]). relacion([sujeto(['Inter-molecule', disulfide, bonds, are, present, in, the, tetramer, but, are, not]), verbo([required]), complemento([for, the, octamer, assembly, and, necroptosis])]). relacion([sujeto(['MLKL', forms, oligomers, in, the, 'necrosome,', and, is, then]), verbo([released]), complemento([from, the, necrosome, before, or, during, its, membrane, translocation])]). relacion([sujeto(['These', data, allowed, us, to, propose, a, 180, °, symmetry, model, of, the, 'MLKL', octamer, and, concluded, that, the, fully, assembled, 'MLKL', 'octamers,', but, not, the, previously, described, tetramers]), verbo([act]), complemento([as, effectors, of, necroptosis])]). relacion([sujeto(['Most', 'EPEC', and, 'non-O157', 'EHEC', strains]), verbo([express]), complemento([lymphostatin, '(', also, known, as, 'LifA),', a, 'chromosomally-encoded', 365, kDa, protein])]). relacion([sujeto(['Using', purified, recombinant, 'protein,', we, demonstrated, that, lymphostatin]), verbo([inhibits]), complemento(['mitogen-activated', proliferation, of, bovine, 'T', 'cells,', and, to, a, lesser, extent, proliferation, of, 'cytokine-stimulated', 'B', 'cells,', but, not, 'NK', cells])]). relacion([sujeto(['It', broadly, affected, the, 'T', cell, 'compartment,']), verbo([inhibiting]), complemento([all, cell, subsets, '(', 'CD4,', 8, ',', 'WC-1', and, 'γδ-TCR)', and, cytokines, examined, '(', 'IL-2,', -, 4, ',', -, 10, ',', -, 17, 'A', and, 'IFN-γ),', and, rendered, 'T', cells, refractory, to, mitogen, for, a, least, 18, hours, after, transient, exposure])]). relacion([sujeto(['Lymphostatin', was, also, able, to]), verbo([inhibit]), complemento([proliferation, of, 'T', cells, stimulated, by, 'IL-2', and, by, antigen, presentation, using, a, 'Theileria-transformed', cell, line, and, autologous, 'T', cells, from, 'Theileria-infected', cattle])]). relacion([sujeto(['We', conclude, that, lymphostatin, is, likely, to]), verbo([act]), complemento([early, in, 'T', cell, 'activation,', as, stimulation, of, 'T', cells, with, concanavilin, 'A,', but, not, phorbol, 12, -, myristate, 13, -, acetate, combined, with, 'ionomycin,', was, inhibited])]). relacion([sujeto([coli, 'O157:H7', '(', 'ToxB,', 'L7095)', was, also]), verbo([found]), complemento([to, possess, comparable, inhibitory, activity, against, 'T', 'cells,', indicating, a, potentially, conserved, strategy, for, interference, in, adaptive, responses, by, attaching, and, effacing, 'E'])]). relacion([sujeto(['The', 'BBB', separates, blood, components, from, the, brain, 'microenvironment,']), verbo([regulating]), complemento([the, entry, and, exit, of, 'ions,', 'nutrients,', 'macromolecules,', and, energy, metabolites])]). relacion([sujeto(['Over', the, last, two, 'decades,', physiological, studies, of, cerebral, blood, flow, dynamics]), verbo([have]), complemento([demonstrated, that, substantial, intercellular, communication, occurs, between, cells, of, the, vasculature, and, the, neurons, and, glia, that, abut, the, vasculature])]). relacion([sujeto(['These', findings]), verbo([suggest]), complemento([that, the, 'BBB', does, not, function, 'independently,', but, as, a, module, within, the, greater, context, of, a, multicellular, neurovascular, unit, '(', 'NVU)', that, includes, 'neurons,', 'astrocytes,', 'pericytes,', and, microglia, as, well, as, the, blood, vessels, themselves])]). relacion([sujeto(['Here,', we, describe, the, roles, of, these, 'NVU', components, as, well, as, how, they]), verbo([act]), complemento([in, concert, to, modify, cerebrovascular, function, and, permeability, in, health, and, select, diseases])]). relacion([sujeto(['The', updated, guidance, states, that, '\'', '[', 'c]ountry', health, programmes, should]), verbo([ensure]), complemento(['that…', '[', 'i]n', order, to, prevent, adverse, pregnancy, and, fetal, 'outcomes,', men, and, women, of, reproductive, 'age,', living, in, areas, where, local, transmission, of, 'Zika', virus, is, known, to, 'occur,', be, correctly, informed, and, oriented, to, consider, delaying, 'pregnancy\''])]). relacion([sujeto(['While', the, media]), verbo([has]), complemento([reported, this, advice, as, 'WHO', telling, couples, in, 'Zika-affected', regions, to, avoid, 'pregnancy,', 'WHO', states, that, they, are, not, doing, that])]). relacion([sujeto(['In', this, 'statement,', the, 'WHO\'s', spokesperson, distinguishes, between, actively, directing, individuals, to, delay, pregnancy, and, advising, 'them,', which, is, portrayed, as, a, merely, informative]), verbo([act]), complemento([that, facilitates, but, does, not, direct, an, 'individual\'s', final, decision])]). relacion([sujeto(['Cell', signaling, pathways]), verbo([mediated]), complemento([by, 'leucine-rich', repeat, 'receptor-like', kinases, '(', 'LRR-RLK)', are, essential, for, plant, 'growth,', development, and, defense])]). relacion([sujeto(['Here,', we, show, that, 'SERK1', '(', 'SOMATIC', 'EMBRYOGENESIS', 'RECEPTOR-LIKE', 'KINASE1)', and, 'SERK2', 'LRR-RLKs']), verbo([act]), complemento([redundantly, as, 'co-regulatory', and, physical, partners, of, 'EMS1'])]). relacion([sujeto(['Bimolecular', fluorescence, complementation, '(', 'BiFC),', 'Förster', resonance, energy, transfer, '(', 'FRET),', and, 'co-immunoprecipitation', '(', 'co-IP)', approaches, revealed, that, 'SERK1', biochemically]), verbo([interacted]), complemento([with, 'EMS1'])]). relacion([sujeto(['Trans-phosphorylation', of, 'EMS1', by, 'SERK1']), verbo([enhances]), complemento(['EMS1', kinase, activity])]). relacion([sujeto(['Among', twelve, in, vitro, 'auto-', and, 'trans-phosphorylation', sites, identified, by, tandem, mass, 'spectrometry,', seven, of, them, were]), verbo([found]), complemento([to, be, critical, for, 'EMS1', 'auto-phosphorylation', activity])]). relacion([sujeto(['Furthermore,', complementation, test, results]), verbo([suggest]), complemento([that, phosphorylation, of, 'EMS1', is, required, for, its, function, in, anther, development])]). relacion([sujeto(['Collectively,', these, data]), verbo([provide]), complemento([genetic, and, biochemical, evidence, on, the, interaction, and, phosphorylation, between, 'SERK1/2', and, 'EMS1', in, anther, development])]). relacion([sujeto(['In', 'monkeys,', motor, outputs, from, premotor, cortex, '(', 'PM)']), verbo([involve]), complemento(['cortico-cortical', connections, with, primary, motor, cortex, '(', 'M1)'])]). relacion([sujeto(['vlPM-BA6', was]), verbo([found]), complemento([to, be, less, 'excitable,', with, significantly, longer, 'MEP', latencies, than, 'M1'])]). relacion([sujeto(['The', longer, latency, of, 'vlPM-BA6', 'MEPs']), verbo([suggests]), complemento([that, human, vlPM, could, act, on, spinal, motoneurons, either, directly, through, more, slowly, conducting, 'CST', fibers, or, via, less, direct, pathways, through, 'M1,', 'brainstem,', or, spinal, mechanisms])]). relacion([sujeto(['Even', though, splicing, repression, by, hnRNP, complexes]), verbo([bound]), complemento([to, exonic, sequences, is, 'well-documented,', the, responsible, effector, domains, of, hnRNP, proteins, have, been, described, for, only, a, select, number, of, hnRNP, constituents])]). relacion([sujeto(['We', also, show, that, all, four, hnRNP, 'D', isoforms, can]), verbo([act]), complemento([as, genuine, splicing, repressors, when, bound, to, exonic, positions])]). relacion([sujeto(['Moreover,', we, demonstrate, that, hnRNP, 'D', proteins]), verbo([associate]), complemento([with, the, 'HIV-1', 'ESSV', silencer, 'complex,', probably, through, direct, recognition, of, &, 'quot;UUAG"', sequences, overlapping, with, the, previously, described, &, 'quot;UAGG"', motifs, bound, by, hnRNP, 'A1'])]). relacion([sujeto(['Consequently,', this, spatial, proximity, seems, to]), verbo([cause]), complemento([mutual, interference, between, hnRNP, 'A1', and, hnRNP, 'D'])]). relacion([sujeto([1, ')', from, strain, 'Leuconostoc', mesenteroides, 326, ',', which, synthesizes, dextran, and, 'oligosaccharides,', which]), verbo([act]), complemento([as, 'prebiotics,', are, popularly, used, in, such, industries, as, food, and, medicine])]). relacion([sujeto(['The', novel, enzyme, '(', 'MW:', 110, 'kDa)']), verbo([loss]), complemento(['activity,', when, sucrose, was, used, as, only, substrate])]). relacion([sujeto(['After', adding, an, 'acceptor,', 'DSR-S1-ΔA', was, fully]), verbo([activated]), complemento([but, with, heavily, impaired, polysaccharide, synthesis, ability])]). relacion([sujeto(['Since', the, ratio, between, the, two, forms, of, glutathione, '(', 'GSH/GSSG)', is, important, for, the, optimal, function, of, 'GSH', to]), verbo([act]), complemento([as, an, antioxidant, against, 'H2O2,', the, contribution, of, 'GSR', as, an, enzymatic, regulatory, agent, to, maintain, the, proper, ratio, is, essential])]). relacion([sujeto(['Abalones', are, marine, mollusks, that, frequently, encounter, environmental, factors, that, can]), verbo([trigger]), complemento([the, overproduction, of, reactive, oxygen, species, '(', 'ROS)', such, as, 'H2O2'])]). relacion([sujeto(['Therefore,', we, conducted, the, current, study, to]), verbo([reveal]), complemento([the, molecular, and, functional, properties, of, a, 'GSR', homolog, in, the, disk, 'abalone,', 'Haliotis', discus, discus])]). relacion([sujeto(['The', identified, cDNA, sequence, '(', 2325, 'bp)']), verbo([has]), complemento([a, 1356, bp, long, open, reading, frame, '(', 'ORF),', coding, for, a, 909, bp, long, amino, acid, 'sequence,', which, harbors, a, pyridine, 'nucleotide-disulfide', oxidoreductase, domain, '(', 171, -, 246, 'aa),', a, pyridine, 'nucleotide-disulfide', oxidoreductase, dimerization, 'domain,', and, a, 'NAD(P)(+)-binding', 'Rossmann', fold, superfamily, signature, domain])]). relacion([sujeto(['Four', functional, 'residues:', the, 'FAD']), verbo([binding]), complemento(['site,', glutathione, binding, 'site,', 'NADPH', binding, 'motif,', and, assembly, domain, were, identified, to, be, conserved, among, the, other, species])]). relacion([sujeto(['The', optimum, pH, and, optimal, temperature, for, the, reaction, were]), verbo([found]), complemento([to, be, 7.0, and, 50, &, 'nbsp;°C,', 'respectively,', while, the, ionic, strength, of, the, medium, had, no, effect])]). relacion([sujeto(['The', enzymatic, reaction, was, vastly]), verbo([inhibited]), complemento([by, 'Cu(+2)', and, 'Cd(+2)', ions])]). relacion([sujeto(['Furthermore,', 'AbGSR', was]), verbo([found]), complemento([to, be, ubiquitously, distributed, in, different, types, of, abalone, tissues])]). relacion([sujeto(['Taken', 'together,', the, results, of, the, current, study]), verbo([suggest]), complemento([that, 'AbGSR', plays, an, important, role, in, 'antioxidant-mediated', host, defense, mechanisms, and, also, provide, insights, into, the, immunological, contribution, of, 'AbGSR'])]). relacion([sujeto(['Programmed', cell, clearance, is, a, highly]), verbo([regulated]), complemento([physiological, process, of, elimination, of, dying, cells, that, occurs, rapidly, and, efficiently, in, healthy, organisms])]). relacion([sujeto(['It', thus]), verbo([ensures]), complemento([proper, development, as, well, as, homeostasis])]). relacion([sujeto(['Recent', studies]), verbo([have]), complemento([disclosed, a, considerable, degree, of, conservation, of, cell, clearance, pathways, between, nematodes, and, higher, organisms])]). relacion([sujeto(['The', externalization, of, the, anionic, phospholipid, phosphatidylserine, '(', 'PS)']), verbo([has]), complemento([emerged, as, an, important, &, 'quot;eat-me"', signal, for, phagocytes, and, its, exposition, on, apoptotic, cells, is, controlled, by, phospholipid, translocases, and, scramblases])]). relacion([sujeto(['However,', there, is, mounting, evidence, that, 'PS', exposure, occurs, not, only, in, 'apoptosis,', but, may, also, be, actively]), verbo([expressed]), complemento([on, the, surface, of, cells, undergoing, other, forms, of, cell, death, including, 'necrosis;', 'PS', is, also, expressed, on, the, surface, of, engulfing, cells])]). relacion([sujeto(['Additionally,', 'PS', may]), verbo([act]), complemento([as, a, &, 'quot;save-me"', signal, during, axonal, regeneration])]). relacion([sujeto(['It']), verbo([has]), complemento([many, 'functions,', including, neural, induction, and, patterning, of, the, ectoderm, and, mesoderm])]). relacion([sujeto(['Here', we, undertake, a, functional, screen, to, discover, new, secreted, factors]), verbo([expressed]), complemento([by, the, node, at, this, time, of, development])]). relacion([sujeto(['We', show, that, in, addition, to, its, known, functions, in, intracellular, 'Calcium', regulation, and, protein, 'folding,', 'Calreticulin', is, 'secreted,', it, can]), verbo([bind]), complemento([to, 'BMP4', and, act, as, a, 'BMP', antagonist, in, vivo, and, in, vitro])]). relacion([sujeto(['To', 'date,', many, striking, results]), verbo([have]), complemento([demonstrated, serpins, are, involved, in, the, invertebrate, immune, system, by, regulating, the, proteolytic, cascades])]). relacion([sujeto(['Sequence', alignments]), verbo([have]), complemento([indicated, that, 'Apserpin-3', might, regulate, the, melanization, reaction, via, inhibiting, 'prophenoloxidases-activating', 'protease(s)', in, plasma])]). relacion([sujeto(['Furthermore,', it, was, detected, to, be, primarily]), verbo([transcribed]), complemento([within, the, fat, 'body,', epidermis, and, hemocytes, with, significant, induction, following, 'immune-challenge'])]). relacion([sujeto(['Further', studies]), verbo([have]), complemento([shown, that, the, knockdown, of, 'serpin-3', 'up-regulated', the, prophenoloxidases, cascade, stimulated, by, pathogen, in, 'hemolymph,', while, the, addition, of, recombinant, 'serpin-3', along, with, the, same, elicitor, led, to, the, suppressed, activation, of, prophenoloxidase])]). relacion([sujeto(['Besides,', the, injection, of, dsRNA, of, 'serpin-3']), verbo([caused]), complemento([the, elevated, expression, of, antimicrobial, peptides])]). relacion([sujeto(['Altogether,', we, arrived, at, a, conclusion, that, 'serpin-3', might]), verbo([act]), complemento([as, a, 'negative-regulator', in, prophenoloxidases, activation, and, inhibit, the, production, of, antimicrobial, peptides, in, 'Antheraea', pernyi, larvae])]). relacion([sujeto(['Distal', vessel, calcification]), verbo([has]), complemento([been, shown, to, be, a, major, factor, in, causing, 'CHI'])]). relacion([sujeto(['Obtaining', good, outflow, to, the, fingers, is, critical, for, wound, healing, and]), verbo([preventing]), complemento([amputation])]). relacion([sujeto(['The', magnitude, of, the, clinical, benefits, produced, by, inhibitors, of, the, 'renin-angiotensin', system, in, heart, failure]), verbo([has]), complemento([been, 'modest,', possibly, because, of, the, ability, of, 'renin-angiotensin', activity, to, escape, from, suppression, during, 'long-term', treatment])]). relacion([sujeto(['Efforts', to, intensify, pharmacological, blockade, by, use, of, dual, inhibitors, that, interfere, with, the, 'renin-angiotensin', system, at, multiple, sites]), verbo([have]), complemento([not, yielded, consistent, incremental, clinical, 'benefits,', but, have, been, associated, with, serious, adverse, reactions])]). relacion([sujeto(['By', 'contrast,', potentiation, of, endogenous, compensatory, vasoactive, peptides, can]), verbo([act]), complemento([to, enhance, the, survival, effects, of, inhibitors, of, the, 'renin-angiotensin', 'system,', as, evidenced, by, trials, that, have, compared, 'angiotensin-converting', enzyme, inhibitors, with, drugs, that, inhibit, both, the, 'renin-angiotensin', system, and, neprilysin])]). relacion([sujeto(['Several', endogenous, vasoactive, peptides]), verbo([act]), complemento([as, adaptive, 'mechanisms,', and, their, augmentation, could, help, to, broaden, the, benefits, of, 'renin-angiotensin', system, inhibitors, for, patients, with, heart, failure])]). relacion([sujeto(['Initially,', the, 'FDA', authority, was, restricted, to, issues, of, safety, and, only, later, did, the, documentation, of, efficacy, become, part, of, the, review, process]), verbo([required]), complemento([for, approval])]). relacion([sujeto(['However,', all, drugs]), verbo([have]), complemento([the, potential, for, causing, harm, at, some, dose, level, to, all, and, at, lower, doses, in, certain, patients, with, vulnerability, to, the, particular, pharmacology, of, the, agent])]). relacion([sujeto(['As', new, drugs]), verbo([have]), complemento([been, designed, to, manage, disorders, that, are, 'uncommon,', but, of, significant, 'consequence,', they, may, have, adverse, effects, that, are, acceptable, only, because, they, are, so, uniquely, beneficial, to, these, specific, conditions])]). relacion([sujeto(['The', approval, of, this, category, of, drugs]), verbo([has]), complemento([grown, rapidly, since, definition, of, a, mechanism, of, action, to, manage, and, modify, the, risk, has, been, provided, by, a, process, known, as, known, as, 'Risk', 'Evaluation', and, 'Mitigation', 'Strategy', or, &, 'quot;REMS'])]). relacion([sujeto([&, 'quot;', 'In', 2007, ',', the, 'Food', and, 'Drug', 'Administration', 'Amendments', 'Act', '(', 'FDAAA)', allowed, the, 'FDA', to]), verbo([require]), complemento([postmarketing, studies, and, the, authority, to, mandate, the, implementation, of, a, 'REMS', for, drugs, with, efficacy, but, documented, potential, for, harm])]). relacion([sujeto(['Two', relatively, new, drugs, useful, in, the, management, of, severe, elevations, of, 'low-density', lipoprotein, cholesterol]), verbo([have]), complemento([been, approved, under, a, requirement, for, a, 'REMS'])]). relacion([sujeto(['We', assessed, the, presence, and, severity, of, fatigue, in, patients, with, 'JIA,', including, factors, presumed]), verbo([associated]), complemento([with, fatigue, '(', e])]). relacion([sujeto(['The', current, study, used, baseline, data, of, 80, patients, with, 'JIA', '(', age, 8, -, 13, ')', who]), verbo([participated]), complemento([in, an, intervention, aimed, at, promoting, physical, activity])]). relacion([sujeto(['Self-efficacy', was, a, predictor, of, fatigue, but, did, not]), verbo([act]), complemento([as, moderator])]). relacion([sujeto(['Interventions', aimed, at, reducing, perceived, 'disability,']), verbo([stimulating]), complemento([physical, 'activity,', and, enhancing, 'self-efficacy', might, reduce, fatigue, and, thereby, enhance, participation])]). relacion([sujeto(['The', implementation, of, nutrition, policies, in, schools]), verbo([has]), complemento([been, recommended, as, a, strategy, to, improve, child, dietary, intake])]). relacion([sujeto(['Internationally,', research]), verbo([suggests]), complemento([that, the, majority, of, schools, do, not, implement, these, policies])]). relacion([sujeto(['In', 'New', 'South', 'Wales', '(', 'NSW),', 'Australia,', the, 'NSW', 'Healthy', 'School', 'Canteen', 'Policy']), verbo([requires]), complemento([that, school, canteens, prohibit, the, sale, of, '\'', 'red\'', foods, '(', i])]). relacion([sujeto(['Intervention', schools, received, an, initial, face, to, face, contact, and, up, to, four, cycles, of, audit, and, feedback, '(', consisting, of, a, menu, 'audit,', written, feedback]), verbo([report]), complemento([and, telephone, 'feedback)', over, a, 12, -, month, period])]). relacion([sujeto(['Intervention', schools, were, significantly, more, likely, to]), verbo([have]), complemento([a, lower, percentage, of, '\'', 'red\'', items, '(', 'p-value:', 0.007, ')', and, a, higher, percentage, of, '\'', 'green\'', items, on, the, menu, '(', 'p-value:', 0.014, ')'])]). relacion([sujeto(['While', there, was, insufficient, statistical, evidence, to]), verbo([suggest]), complemento([that, this, multicomponent, audit, and, feedback, intervention, was, effective, in, improving, primary, 'schools\'', compliance, with, a, healthy, canteen, 'policy,', the, intervention, demonstrated, some, positive, impact, in, reducing, the, availability, of, '\'', 'red\'', items, on, the, menu])]). relacion([sujeto(['The', recent]), verbo([finding]), complemento([of, asbestos, fibres, in, drinking, water, '(', up, to, 700.0, 'fibres/litres)', in, 'Tuscany', '(', 'Central', 'Italy)', leads, to, concerns, about, health, risks, in, exposed, communities])]). relacion([sujeto(['Exposure', to, asbestos]), verbo([has]), complemento([been, linked, with, cancer, at, several, levels, of, the, gastrointestinal, 'tract,', and, it, has, been, 'documented,', in, an, animal, 'model,', a, direct, cytotoxic, effect, of, asbestos, fibres, on, the, ileum])]). relacion([sujeto(['It']), verbo([has]), complemento([been, recently, described, a, possible, link, between, asbestos, and, intrahepatic, 'cholangiocarcinoma,', and, asbestos, fibres, have, been, detected, in, humans, in, histological, samples, from, colon, cancer, and, in, gallbladder, bile])]). relacion([sujeto(['Taken', 'together,', these, findings]), verbo([suggest]), complemento([the, possibility, of, an, enterohepatic, translocation, of, asbestos, 'fibres,', alternative, to, lymphatic, translocation, from, lungs])]). relacion([sujeto(['In', animal, 'models,', asbestos, fibres, ingested, with, drinking, water]), verbo([act]), complemento([as, a, 'co-carcinogen', in, the, presence, of, 'benzo(a)', pyrene, 'and,', according, to, the, 'International', 'Agency', for, 'Research', on, 'Cancer', '(', 'IARC', ')', ',', there, is, evidence, pointing, to, a, causal, effect, of, ingested, asbestos, on, gastric, and, colorectal, cancer])]). relacion([sujeto(['Furthermore,', the, exposure, to, asbestos, by, ingestion, could, explain, the, epidemiological]), verbo([finding]), complemento([of, mesothelioma, in, subjects, certainly, unexposed, by, inhalation])]). relacion([sujeto(['In', 'conclusion,', several, findings]), verbo([suggest]), complemento([that, health, risks, from, asbestos, could, not, exclusively, derive, from, inhalation, of, fibres])]). relacion([sujeto(['Health', professionals, face, serious, legal, risks, if, they]), verbo([act]), complemento([as, 'go-betweens', for, researchers, seeking, participants, for, clinical, 'trials,', the, 'RCN', 'Research', 'Society\'s', conference, was, told])]). relacion([sujeto(['A', study]), verbo([has]), complemento([shown, that, patients])]). relacion([sujeto(['Two', recent]), verbo([reports]), complemento([offer, an, interesting, contrast, regarding, provision, of, mental, health, services])]). relacion([sujeto(['One', supports, the, idea, of, legislation, to, improve, 'services,', whereas, the, other, calls, upon, services, to, get, their]), verbo([act]), complemento([together])]). relacion([sujeto(['Because', 'PSA', glycosylation, is, altered, by, prostate, 'cancer,', detecting, glycosylation, changes, could]), verbo([increase]), complemento(['PSA', specificity, as, a, prostate, cancer, marker])]). relacion([sujeto(['To']), verbo([have]), complemento([access, to, most, of, the, 'PSA,', the, complexed, 'PSA', has, to, be, released, as, free, 'PSA', '(', 'fPSA);', in, 'addition,', this, total, fPSA, must, be, purified, from, the, serum, matrix, so, that, it, can, be, analyzed, using, 'CZE'])]). relacion([sujeto(['Ten', national, level, male, water, polo, players]), verbo([executed]), complemento([eggbeater, kicks, at, maximum, effort, for, the, duration, of, the, test])]). relacion([sujeto(['A']), verbo([decrease]), complemento([in, 'CCI', was, observed, with, fatigue, for, 'FLX2', while, 'AV', was, reduced, for, all, phases])]). relacion([sujeto(['During', the, cycle, 'RF', and, 'BF']), verbo([act]), complemento([as, 'agonist/antagonist', to, accelerate, and, decelerate, knee, 'flexion/extension'])]). relacion([sujeto(['The', high, 'AV', and, low, 'CCI', levels, observed, for, 'EXT2', might]), verbo([increase]), complemento([joint, instability, and, consequent, risk, of, injury])]). relacion([sujeto(['This', knowledge]), verbo([provides]), complemento([a, better, understanding, of, the, mechanisms, involved, in, stabilizing, and, controlling, the, knee, during, underwater, movement])]). relacion([sujeto(['After', sudden, traumatic, brain, 'injuries,', secondary, injuries, may, occur, during, the, following, days, or, 'weeks,', which]), verbo([leads]), complemento([to, the, accumulation, of, reactive, oxygen, species, '(', 'ROS)'])]). relacion([sujeto(['Zinc', finger, protein, 179, '(', 'Znf179)', was, shown, to]), verbo([act]), complemento([as, a, neuroprotective, 'factor,', but, the, regulation, of, gene, expression, under, oxidative, stress, remains, unknown])]). relacion([sujeto(['In', this, 'study,', we, demonstrated, an]), verbo([increase]), complemento([in, 'Znf179', protein, levels, in, both, in, vitro, model, of, hydrogen, peroxide, '(', 'H2O2)-induced', 'ROS', accumulation, and, animal, models, of, traumatic, brain, injury])]). relacion([sujeto(['Additionally,', we, examined, the, 'sub-cellular', localization, of, 'Znf179,', and, demonstrated, that, oxidative, stress]), verbo([increases]), complemento(['Znf179', nuclear, shuttling, and, its, interaction, with, specificity, protein, 1, '(', 'Sp1)'])]). relacion([sujeto(['The', upregulation, of, 'Sp1', transcriptional, activity]), verbo([induced]), complemento([by, the, treatment, with, nerve, growth, factor, '(', 'NGF)', led, to, an, increase, in, 'Znf179', 'levels,', which, further, protected, cells, against, 'H2O2-induced', damage])]). relacion([sujeto(['However,', 'Sp1', 'inhibitor,', mithramycin, 'A,', was, shown, to]), verbo([inhibit]), complemento(['NGF', 'effects,', leading, to, a, decrease, in, 'Znf179', expression, and, lower, cellular, protection])]). relacion([sujeto(['Mosquitoes']), verbo([act]), complemento([as, vectors, of, key, pathogens, and, parasites])]). relacion([sujeto(['Plant', essential, oils]), verbo([have]), complemento([been, recognized, as, important, sources, of, 'biopesticides,', which, do, not, induce, resistance, and, have, limited, toxic, effects, on, human, health, and, 'non-target', organisms])]). relacion([sujeto(['Voltage-gated', inward, 'Ca(2+)', currents, '(', 'ICa)', are]), verbo([triggered]), complemento([by, cell, depolarization, and, commonly, produce, transient, increases, in, the, cytoplasmic, free, 'Ca(2+)', concentration])]). relacion([sujeto(['Stem', cells, from, the, apical, papilla, '(', 'SCAPs)']), verbo([has]), complemento([a, capacity, for, differentiation, into, the, 'odontoblastic-like', cells, in, vitro, and, dentin, forming, in, 'vivo,', which, makes, 'SCAPs', advantages, in, tissue, engineering, and, regenerative, endodontic])]). relacion([sujeto(['The', transfected, apical, papilla, cells, were]), verbo([induced]), complemento([to, differentiate, into, the, 'odontoblast-like', 'cells,', and, the, expression, of, markers, for, odontoblastic, differentiation, were, analyzed, by, alizarin, red, 'staining,', 'Real-time', 'Polymerase', chain, reaction, '(', 'RT-PCR),', and, 'Western', blot, analysis])]). relacion([sujeto([2, and, excess, expression, of, 'DCT', both]), verbo([suppressed]), complemento([the, expression, of, 'DSPP,', 'ALP', in, mRNA, level, and, the, formation, of, calcium, nodules])]). relacion([sujeto(['Our', results]), verbo([suggest]), complemento([that, 'CaV1'])]). relacion([sujeto([2, and, 'DCT', play, important, roles, in, the, differentiation, of, 'rSCAPs,', 'DCT', might]), verbo([act]), complemento([as, a, transcription, factor, and, regulate, the, differentiation, of, rSCAPs])]). relacion([sujeto(['Resistance', to, benznidazole, in, certain, strains, of, 'Trypanosoma', cruzi, may, be]), verbo([caused]), complemento([by, the, increased, production, of, enzymes, that, act, on, the, oxidative, 'metabolism,', such, as, mitochondrial, tryparedoxin, peroxidase, '(', 'mTcTXNPx)', which, catalyses, the, reduction, of, peroxides])]). relacion([sujeto(['The', last, four, strains]), verbo([have]), complemento([been, recently, isolated, from, triatominae, and, mammalian, host, '(', domestic, 'cat)'])]). relacion([sujeto(['The', expression, of, the, 25.5, kDa, polypeptide, of, mTcTXNPx, did, not]), verbo([increase]), complemento([in, strains, that, were, more, resistant, to, the, ferrocenyl, compounds, '(', 'SI8', and, 'SIGR3)'])]). relacion([sujeto(['In', 'addition,', a, 58, kDa, polypeptide, was, also]), verbo([recognized]), complemento([in, all, strains])]). relacion([sujeto(['Ferrocenyl', diamine, hydrochlorides, showed, trypanocidal, activity, and, the, expression, of, 25.5, kDa, mTcTXNPx, is, not, necessarily]), verbo([increased]), complemento([in, some, 'T'])]). relacion([sujeto(['Most', 'likely,', other, 'mechanisms,', in, addition, to, the, over, expression, of, this, antioxidative, 'enzyme,', should, be]), verbo([involved]), complemento([in, the, escape, of, parasites, from, cytotoxic, oxidant, agents])]). relacion([sujeto([5, ')', for, heart, 'rate,', sympathovagal, balance, and, body, fat, percentage, '(', 'BF%)', such, that, all, significantly]), verbo([decreased]), complemento(['(', 'P<0'])]). relacion([sujeto([5, ')', ;, and, 'R-R', intervals, which, significant]), verbo([increased]), complemento(['(', 'P<0'])]). relacion([sujeto(['The', improvement, in, 'BF%', partially, explained, the]), verbo([decrease]), complemento([in, sympathovagal, balance])]). relacion([sujeto(['Since', obese, and, older, individuals, are, at]), verbo([increased]), complemento([risk, of, developing, cardiovascular, 'diseases,', they, could, potentially, benefit, from, 'WBVT'])]). relacion([sujeto(['Class', 1]), verbo([involved]), complemento([higher, initial, levels, of, 'MVPA', and, linear, decreases, in, 'MVPA', over, 'time,', whereas, 'Class', 2, involved, lower, initial, levels, of, 'MVPA', and, linear, increases, in, 'MVPA', over, time])]). relacion([sujeto(['Levels', of, 'MVPA', change, over, time, in, persons, with, 'RRMS', and, the, pattern, of, change]), verbo([suggests]), complemento([that, behavioral, physical, activity, interventions, for, persons, with, 'MS', might, target, men, and, those, with, lower, disability])]). relacion([sujeto(['We', investigated, the, differences, and, over, time, changes, in, recommended, physical, activity, among, 'foreign-born', '(', 'FB)', from, 'English', speaking, countries, '(', 'ESC)', and, 'non-English', speaking, countries, '(', 'NESC)', relative, to, 'native-born', '(', 'NB)', 'Australians,', and, whether, the, association, between, nativity, and, duration, of, residence, '(', 'DoR)', and, physical, activity, is]), verbo([mediated]), complemento([by, 'English', language, 'proficiency,', 'socio-economic', status, and, social, 'engagement/membership'])]). relacion([sujeto(['We', also]), verbo([found]), complemento([a, mediating, role, of, 'English', language, proficiency, on, immigrants, physical, activities])]). relacion([sujeto([1, 'Low', physical, activity]), verbo([has]), complemento([been, associated, with, 'non-communicable', disease, risk, factors, and, previous, research, suggests, that, urbanicity, might, be, an, important, determinant, of, physical, activity])]). relacion([sujeto(['The', aim, of, this, study, was, to, measure, urbanicity, in, 'Mexico', and, assess, if, it, is]), verbo([associated]), complemento([with, physical, activity, and, sitting, time])]). relacion([sujeto(['The', 'sub-scores', of, 'demographic,', economic, 'activity,', diversity, and, communication, were, negatively]), verbo([associated]), complemento([with, physical, activity])]). relacion([sujeto(['Sitting', time, was, positively]), verbo([associated]), complemento([with, the, overall, 'urbanicity,', and, the, demographic, and, health, 'sub-scores'])]). relacion([sujeto(['Our', findings]), verbo([suggest]), complemento([that, the, 'PAQ', can, reasonably, be, used, in, this, 'oldest-old', population, to, rank, their, 'PA', level])]). relacion([sujeto(['PA', was, negatively]), verbo([associated]), complemento([with, depressive, symptoms, for, the, overall, sample, '(', 'ηp(2)=', 0.04, ',', 'p<0'])]). relacion([sujeto(['For', people, who, were, healthy, '(', 'BMI', 18.5, -, 24.9, ')', or, overweight, '(', 'BMI', 25, -, 29.9, ')', ',', high, amounts, of, 'PA', were, significantly]), verbo([associated]), complemento([with, fewer, depressive, 'symptoms;', for, adults, who, were, obese, '(', 'BMI', '≥', 30, ')', 'however,', both, moderate, and, high, amounts, were, associated, with, fewer, depressive, symptoms])]). relacion([sujeto(['PA', is]), verbo([associated]), complemento([with, fewer, depressive, symptoms, among, adults, with, 'Type', 2, 'DM,', however, the, amount, of, 'PA', associated, with, fewer, depressive, symptoms, varies, according, to, weight, status])]). relacion([sujeto(['Lower', amounts, of, 'PA', might, be]), verbo([required]), complemento([for, people, who, are, obese, to, achieve, meaningful, reductions, in, depressive, symptoms, compared, to, those, who, are, healthy, weight, or, overweight])]). relacion([sujeto(['Sedentary', behavior, '(', 'SB)']), verbo([increases]), complemento([throughout, 'adolescence,', and, is, associated, with, adverse, health, outcomes])]). relacion([sujeto(['Screen', time, was]), verbo([associated]), complemento([with, greater, screen, time, 'enjoyment,', lower, 'self-efficacy,', and, 'friends\'', screen, time, '(', 'r(2)='])]). relacion([sujeto(['Interventions', should, place, an, emphasis, on, encouraging, less, screen, 'time,', and]), verbo([providing]), complemento([opportunities, for, adolescents, and, their, friends, to, engage, in, activities, that, promote, physical, activity, rather, than, 'SB'])]). relacion([sujeto(['This', study, examined, associations, between, sedentary, 'time,', physical, activity, '(', 'PA),', and, executive, function, among, youth]), verbo([participating]), complemento([in, the, 'Study', of, 'Early', 'Child', 'Care', and, 'Youth', 'Development'])]). relacion([sujeto(['Sedentary', time, at, 9, yrs, predicted, fluid, intelligence, at, 15, yrs, '(', 'B', =, 0.031, ')', ',', whereas]), verbo([increased]), complemento([sedentary, time, from, 9, to, 15, yrs, predicted, higher, inhibition, '(', 'B', =, 0.003, ')', ',', working, memory, '(', 'B', =, 0.074, ')', ',', and, fluid, intelligence, '(', 'B', =, 0.029, ')'])]). relacion([sujeto(['Relatively', lower, levels, of, working, memory, at, 15, yrs, were, predicted, from]), verbo([increased]), complemento([levels, of, light, 'PA,', moderate, 'PA,', and, 'MVPA', from, 9, to, 15, yrs, '(', 'B', =, -, 0.075, ',', -, 0.293, ',', and, -, 0.173, ',', 'respectively)'])]). relacion([sujeto(['At', 15, 'yrs,', 'inhibition,', working, 'memory,', and, fluid, intelligence, were, significantly]), verbo([associated]), complemento([with, sedentary, time, '(', 'B', =, 0.003, ',', 0.055, ',', and, 0.045, ',', 'respectively)'])]). relacion([sujeto(['Few', studies]), verbo([have]), complemento([examined, the, associations, among, social, 'cohesion,', physical, 'activity,', and, obesity, in, older, adults])]). relacion([sujeto(['Neighborhood', social, cohesion, was, not]), verbo([associated]), complemento([with, obesity, for, older, adults])]). relacion([sujeto(['Aging(Plus)', is, an, 8, -, week, 'multi-component', motivational, program, which]), verbo([promotes]), complemento([increased, physical, activity, by, targeting, 'adults\'', negative, views, on, aging, '(', 'NVOA)', and, perceptions, of, 'control,', two, known, psychological, barriers, to, physical, exercise])]). relacion([sujeto([62, 'adults,', ages, 50, -, 82, 'years,']), verbo([participated]), complemento([in, this, feasibility, study])]). relacion([sujeto(['These', findings]), verbo([provide]), complemento([promising, support, for, the, feasibility, and, efficacy, of, the, 'Aging(Plus)', program])]). relacion([sujeto(['The', prevalence, of, knowledge, about, sufficient, 'PA', to, meet, national, guidelines]), verbo([increased]), complemento(['(', 31, '%', to, 57, '%', ')'])]). relacion([sujeto(['Most', adults, '(', 66, '%', ')']), verbo([reported]), complemento([having, many, safe, places, to, walk, locally])]). relacion([sujeto(['Having', policies, to, encourage, walking, and, cycling, when, redeveloping, communities]), verbo([increased]), complemento([by, community, size, '(', 5, '%', to, 37, '%', ')'])]). relacion([sujeto(['Most', parents, '(', 64, '%', ')']), verbo([provided]), complemento([transportation, to, support, their, 'child\'s', 'PA'])]). relacion([sujeto(['The', prevalence, of, policies, mandating, daily, 'PE']), verbo([increased]), complemento([2001, -, 2011, '(', 36, '%', to, 55, '%', ')', ',', as, did, having, no, policy, to, hire, qualified, 'PE', teachers, '(', 25, '%', to, 34, '%', ')'])]). relacion([sujeto(['Canada\'s', surveillance, system]), verbo([has]), complemento([provided, information, for, guiding, policy, 'planning,', resource, 'allocation,', setting, and, tracking, national, 'goals,', assessing, changes, in, 'PA', 'determinants,', and, evaluating, national, 'campaigns,', naturally, occurring, 'experiments,', and, innovative, policies])]). relacion([sujeto(['Private', 'schools,', which, serve, about, five, million, 'US', children, and, 'adolescents,', may, be, falling, short, in]), verbo([providing]), complemento([quality, 'PE'])]). relacion([sujeto(['Recommended', levels, of, recreation, activity, and, moderate, levels, of, transportation, activity, were]), verbo([associated]), complemento([with, normal, sleep, duration, '(', 'Odds', 'Ratio', '(', 'OR):', =, 1.33, ',', 95, '%', 'Confidence', 'Interval', '(', 'CI)', =, 1.08, ',', 1.65, ;, 'OR=', 1.28, ',', 95, '%', 'CI=', 1.02, ',', 1.62, ',', 'respectively)'])]). relacion([sujeto(['High', occupation, physical, activity, was]), verbo([associated]), complemento([with, shorter, sleep, duration, '(', 'OR', =, 0.59, ',', 95, '%', 'CI', =, 0.49, ',', 0.71, ')'])]). relacion([sujeto(['White', individuals, who, engaged, in, some, recreation, 'activity,', relative, to, being, 'inactive,', had, more, favorable, sleep, 'duration;', 'whereas,', high, levels, of, occupation, activity, were]), verbo([associated]), complemento([with, worse, sleep, duration, among, 'White', and, 'Black', individuals])]). relacion([sujeto(['Physical', activity, was, not]), verbo([associated]), complemento([with, sleep, duration, among, 'Hispanics'])]). relacion([sujeto(['Physical', activity, during, pregnancy]), verbo([has]), complemento([numerous, 'benefits,', but, the, influence, on, the, duration, of, labor, is, unclear])]). relacion([sujeto(['CNDs']), verbo([act]), complemento([as, the, nucleus, to, attract, these, reactive, ions, and, provide, the, luminescent, centers, in, the, hybrid, phosphors])]). relacion([sujeto(['The', new, cationic, '[', '(', 3, -, 'iminophosphine)nickel(allyl)]+', catalysts]), verbo([have]), complemento([been, fully, characterized, and, act, regioselectively, in, the, catalytic, hydroamination, of, allenes, with, secondary, amines, at, room, temperature])]). relacion([sujeto(['Since', dysregulation, of, the, sonic, hedgehog, pathway, plays, an, important, role, in, 'carcinogenesis,', we, aimed, to, assess, whether, members, of, the, sonic, 'hedgehog-signaling', pathway, may]), verbo([act]), complemento([as, prognostic, factors, in, patients, with, 'HPV', negative, head, and, neck, squamous, cell, carcinoma])]). relacion([sujeto(['Cox-multivariate', analysis, showed, that, overexpression, of, 'Gli-2', correlated, independently, '(', 'HR', 0.4, ',', 95, '%', 'CI', 0.16, -, 0.95, ',', p, =, 0.03, ')', with]), verbo([increased]), complemento([overall, survival])]). relacion([sujeto(['Within', 'Drosophila,', 'O-GlcNAc', transferase, '(', 'OGT)', is, one, of, the, 'Polycomb', group, proteins, '(', 'PcGs)', that]), verbo([act]), complemento([through, 'Polycomb', group, response, elements, '(', 'PREs)', to, silence, homeotic, '(', 'HOX)', and, other, 'PcG', target, genes])]). relacion([sujeto(['We']), verbo([find]), complemento([that, 'O-GlcNAc', is, distributed, to, specific, genomic, loci, both, in, cells, and, in, vivo])]). relacion([sujeto(['Loss', of, 'OGT']), verbo([leads]), complemento([to, altered, gene, expression, not, only, at, loci, containing, 'PREs', but, also, at, loci, lacking, 'PREs,', including, several, heterochromatic, genes])]). relacion([sujeto(['These', data]), verbo([suggest]), complemento([that, 'O-GlcNAc', acts, through, multiple, mechanisms, to, regulate, gene, expression, in, 'Drosophila'])]). relacion([sujeto(['Indoor', air, pollution, is, an]), verbo([increasing]), complemento([health, 'concern,', especially, in, enclosed, environments, such, as, underground, subway, stations, because, of, increased, global, usage, by, urban, populations])]). relacion([sujeto(['Results', showed, that, the, 'CO₂,', 'CO', and, 'HCHO', levels, met, the, stipulated, standards, as]), verbo([regulated]), complemento([by, 'Taiwan\'s', 'Indoor', 'Air', 'Quality', 'Management', 'Act', '(', 'TIAQMA)'])]). relacion([sujeto(['TVOCs', and, bacterial, concentrations, at, some, stations, measured, in, summer, were, higher, than, the]), verbo([regulated]), complemento([standards, stipulated, by, 'Taiwan\'s', 'Environmental', 'Protection', 'Administration'])]). relacion([sujeto(['Implementation', of, the, 'Affordable', 'Care', 'Act', '(', 2010, ')', enabled, more, than, 30, million, people, to]), verbo([have]), complemento([new, access, to, primary, care, services])]). relacion([sujeto(['This', imbalance, is, expected, to, 'worsen,', as, the, aging, population]), verbo([requires]), complemento([more, health, care, resources])]). relacion([sujeto(['In', 'addition,', more, patients, are]), verbo([requiring]), complemento([critical, care, services, and, physician, numbers, are, not, keeping, with, this, growing, need])]). relacion([sujeto(['Restrictions', on, resident, physician, practice, hours]), verbo([have]), complemento([impacted, inpatient, care, as, well])]). relacion([sujeto(['Currently,', 21, states, and, the, 'District', of, 'Columbia']), verbo([have]), complemento([adopted, 'FPA', for, 'NPs,', with, 15, more, states, planning, legislation, in, 2016])]). relacion([sujeto(['Given', the, imminent, retirement, of, baby, boomer, 'physicians,', implementation, of, the, 'Affordable', 'Care', 'Act,', and, the]), verbo([increased]), complemento([utilization, of, health, care, services, by, an, 'ever-aging', 'population,', the, supply, of, providers, cannot, keep, pace, with, the, demand, for, services])]). relacion([sujeto(['This']), verbo([has]), complemento([led, to, an, increased, utilization, of, advanced, clinical, practitioners, '(', 'ACPs)'])]). relacion([sujeto(['The', growing, number, of, open, 'ACP', 'positions,', along, with, the, reluctance, to, employ, novice, and, new, graduate, 'ACPs,']), verbo([led]), complemento([to, the, development, of, a, postgraduate, transition, to, practice, fellowship, program])]). relacion([sujeto(['While', the, 'APRN', role, is, more, commonly, accepted, in, primary, 'care,', ambiguity, persists, in, how, to, best, use, the, role, along, the, continuum, of, care, to, achieve, the, 'cost-effective', solutions]), verbo([required]), complemento([in, 'today\'s', health, care, environment])]). relacion([sujeto(['Successful', health, care, systems, of, today, and, tomorrow, are, those, that]), verbo([act]), complemento([boldly, in, a, strategic, direction])]). relacion([sujeto(['Nurse', executives, and, their, nursing, leadership, colleagues, must]), verbo([lead]), complemento([with, evidence, in, hand, to, create, infrastructures, that, support, true, 'integration,', 'optimization,', and, engagement, of, all, members, of, the, provider, team, to, better, serve, our, patients, and, communities])]). relacion([sujeto(['DTSA', can]), verbo([act]), complemento([as, a, potential, host, molecule, with, suitable, guest, molecules, to, develop, new, inclusion, compounds])]). relacion([sujeto(['We']), verbo([report]), complemento([here, the, crystal, structures, of, three, new, polymorphs, of, the, inclusion, compound, of, 'DTSA', and, 'trimethylamine,', namely, trimethylazanium, 2, -, '[', '(', 2, -, 'carboxyphenyl)disulfanyl]benzoate', 2, ',', 2, '\'', -, '(', 'disulfanediyl)dibenzoic', acid, 'monosolvate,', 'C3H10N(+)·C14H9O4S2(-)·C14H10O4S2,', '(', 1, ')', ',', 'tetrakis(trimethylazanium)', 'bis{2-[(2-carboxyphenyl)disulfanyl]benzoate}', 2, ',', 2, '\'', -, '(', 'disulfanediyl)dibenzoate', 2, ',', 2, '\'', -, '(', 'disulfanediyl)dibenzoic', acid, 'monosolvate,', 4, 'C3H10N(+)·2C14H9O4S2(-)·C14H8O4S2(2-)·C14H10O4S2,', '(', 2, ')', ',', and, trimethylazanium, 2, -, '[', '(', 2, -, 'carboxyphenyl)disulfanyl]benzoate,', 'C3H10N(+)·C14H9O4S2(-),', '(', 3, ')'])]). relacion([sujeto(['The', central, 'N', atoms, of, the, guest, amine, molecules, accept, 'H', atoms, from, 'DTSA', molecules, to, give, the, corresponding, 'cations,', which]), verbo([act]), complemento([as, 'counter-ions', to, produce, the, stable, crystal, structures, via, 'N-H'])]). relacion([sujeto(['Using', pharmacological, and, genetic, 'approaches,', we]), verbo([found]), complemento([that, '(', 1, ')', encoding, and, retrieval, of, contextual, memory, requires, mAChR, in, the, dorsal, hippocampus, '(', 'DH)', and, retrosplenial, cortex, '(', 'RSC),', '(', 2, ')', memory, formation, requires, hippocampal, 'M3', and, cooperative, activity, of, 'RSC', 'M1', and, 'M3,', and, '(', 3, ')', memory, retrieval, is, more, impaired, by, inactivation, of, multiple, 'M1-M4', mAChR, in, 'DH', or, 'RSC', than, inactivation, of, individual, receptor, subtypes])]). relacion([sujeto(['Contrary', to, the, view, that, acetylcholine, supports, learning, but, is, detrimental, to, memory, 'retrieval,', we]), verbo([found]), complemento([that, coactivation, of, multiple, mAChR, is, required, for, retrieval, of, both, recently, and, remotely, acquired, context, memories])]). relacion([sujeto(['Manipulations', with, higher, receptor, specificity, were, generally, less, potent, than, manipulations]), verbo([targeting]), complemento([multiple, receptor, 'subtypes,', suggesting, that, mAChR, act, in, synergy, to, regulate, memory, processes])]). relacion([sujeto(['These', findings]), verbo([provide]), complemento([unique, insight, into, the, development, of, therapies, for, amnestic, 'symptoms,', suggesting, that, broadly, 'acting,', rather, than, 'receptor-specific,', mAchR, agonists, and, positive, allosteric, modulators, may, be, the, most, effective, therapeutic, approach])]). relacion([sujeto(['A', cue, with, multiple, sensory, 'qualities,', such, as, a, moving, 'lever-CS,', may]), verbo([activate]), complemento([numerous, neural, pathways, that, process, auditory, and, visual, 'information,', resulting, in, 'CRs', that, vary, both, within, and, between, individuals])]). relacion([sujeto(['We']), verbo([found]), complemento([that, the, multimodal, sensory, features, of, the, 'lever-CS', were, important, to, the, development, and, expression, of, 'sign-tracking'])]). relacion([sujeto(['This', plasticity, in, behavioral]), verbo([responding]), complemento([observed, in, 'STs', closely, resembled, behaviors, normally, seen, in, rats, classified, as, &, 'quot;intermediates'])]). relacion([sujeto([&, 'quot;', 'Furthermore,', the, ability, of, both, the, 'lever-CS', and, the, 'reward-delivery', to, evoke, dopamine]), verbo([release]), complemento([in, the, nucleus, accumbens, was, also, altered, by, covering, the, 'lever-dopamine', signaling, in, 'STs', resembled, neurotransmission, observed, in, rats, that, normally, only, 'GT'])]). relacion([sujeto(['These', data]), verbo([suggest]), complemento([that, while, the, visible, 'lever-CS', was, 'attractive,', 'wanted,', and, had, incentive, value, for, 'STs,', when, presented, in, 'isolation,', the, auditory, component, of, the, cue, was, simply, predictive, of, 'reward,', lacking, incentive, salience])]). relacion([sujeto(['Therefore,', the, specific, sensory, features, of, cues, may, differentially, contribute, to]), verbo([responding]), complemento([and, ensure, behavioral, flexibility])]). relacion([sujeto(['The', growth, of, social, media, and, 'user-created', content, on, online, sites]), verbo([provides]), complemento([unique, opportunities, to, study, models, of, human, declarative, memory])]). relacion([sujeto(['Word', order, was, not]), verbo([found]), complemento([to, be, a, strong, predictor, of, tag, 'use,', and, the, random, permutation, model, performed, comparably, to, the, 'Bayesian', model, without, including, word, order])]). relacion([sujeto(['The', results, of, the, 'large-scale', exploration, show, how, the, architecture, of, the, 2, memory, models, can, be, modified, to, significantly, improve, 'accuracy,', and, may]), verbo([suggest]), complemento(['task-independent', general, modifications, that, can, help, improve, model, fit, to, human, data, in, a, much, wider, range, of, domains])]). relacion([sujeto(['(', 'PsycINFO', 'Database', 'Record', 'Bacterial', spoilage, of, food, products, is]), verbo([regulated]), complemento([by, density, dependent, communication, system, called, quorum, sensing, '(', 'QS)'])]). relacion([sujeto(['QS', control, biofilm, formation, in, numerous, food, pathogens, and, 'Biofilms', formed, on, food, surfaces]), verbo([act]), complemento([as, carriers, of, bacterial, contamination, leading, to, spoilage, of, food, and, health, hazards])]). relacion([sujeto(['Agents']), verbo([inhibiting]), complemento([or, interfering, with, bacterial, 'QS', and, biofilm, are, gaining, importance, as, a, novel, class, of, 'next-generation', food, 'preservatives/packaging', material])]). relacion([sujeto(['Synthesized', nanostructures]), verbo([inhibited]), complemento(['QS', regulated, functions, of, 'C'])]). relacion([sujeto(['NS-ZnNPs', at, 'sub-inhibitory', concentrations]), verbo([inhibited]), complemento([the, biofilm, formation, of, 'four-food', pathogens, viz])]). relacion([sujeto(['Moreover,', 'NS-ZnNPs', was]), verbo([found]), complemento([effective, in, inhibiting, 'pre-formed', mature, biofilms, of, the, four, pathogens])]). relacion([sujeto(['However,', there, is, some, evidence]), verbo([suggesting]), complemento([that, arabinofuranosidases, are, 'substrate-specific,', being, unable, to, display, a, debranching, activity, on, different, polysaccharides])]). relacion([sujeto(['Here,', the, structure, of, 'Clostridium', thermocellum, arabinofuranosidase, 43, 'A', '(', 'CtAbf43A),', which]), verbo([has]), complemento([been, shown, to, act, in, the, removal, of, arabinose, side, chains, from, arabinoxylan, but, not, from, pectic, 'arabinan,', is, reported])]). relacion([sujeto(['CtAbf43A', belongs, to, 'GH43', subfamily, 16, ',', the, members, of, which]), verbo([have]), complemento([a, restricted, capacity, to, attack, xylans])]). relacion([sujeto(['Analysis', of, 'CtAbf43A', along, with, the, other, member, of, 'GH43', subfamily, 16, with, known, 'structure,', the, 'Bacillus', subtilis, arabinofuranosidase, 'BsAXH-m2,3,']), verbo([suggests]), complemento([that, the, specificity, of, subfamily, 16, for, arabinoxylan, is, conferred, by, a, long, surface, 'substrate-binding', cleft, that, is, complementary, to, the, xylan, backbone])]). relacion([sujeto(['The', lack, of, a, 'curved-shaped', 'carbohydrate-interacting', platform, precludes, 'GH43', subfamily, 16, enzymes, from]), verbo([interacting]), complemento([with, the, nonlinear, arabinan, scaffold, and, therefore, from, deconstructing, this, polysaccharide])]). relacion([sujeto(['Temperature', sensitivity, is]), verbo([found]), complemento([in, all, multicelleular, 'organisms,', as, well, as, in, most, primitive, life, forms])]). relacion([sujeto(['Previous', studies]), verbo([have]), complemento([shown, that, 'temperature-based', regulation, is, present, in, the, transcriptional, process, '[', 2, ']'])]). relacion([sujeto(['RNA', 'Thermometers,', 'temperature-sensitive', 'sequences,']), verbo([have]), complemento([been, shown, to, act, on, 'heat-shock', genes, to, regulate, 'temperature-dependant', systems, in, many, organisms, '[', 3, ',', 4, ']'])]). relacion([sujeto(['In', 'addition,', using, the, principle, of, transcriptional, 'thermoregulation,', an, automated, 'temperature-responsive', system]), verbo([stimulating]), complemento([inverse, endothermic, and, exothermic, enzymatic, reactions, for, heat, stabilization, was, proposed])]). relacion([sujeto(['This', system, would, also]), verbo([provide]), complemento([a, synthetic, solution, to, thermoregulation, and, the, current, systems, employed, today])]). relacion([sujeto(['We', are, of, the, view, that, the, framework, does]), verbo([confer]), complemento([protection, for, adolescent, boys, while, enabling, access, to, male, 'circumcision;', 'however,', we, identify, ambiguities, and, tensions, that, exist, between, the, 'Children\'s', 'Act,', regulations, and, national, guidelines])]). relacion([sujeto(['Each', centre, selected, two, speech, and, language, therapists, to]), verbo([act]), complemento([as, knowledge, brokers, whose, role, was, to, raise, awareness, of, 'CPT', in, the, team, and, to, facilitate, getting, partners, of, people, with, aphasia, into, the, programme])]). relacion([sujeto(['Seven', centres, were, successful, in, reaching, the]), verbo([target]), complemento([inclusion, of, six, dyads, in, total])]). relacion([sujeto(['From', a, recruitment, pool, of, 504, 'dyads,', 41, dyads, were]), verbo([recruited]), complemento([and, 34, partners, completed, the, implementation, study, of, the, 'PACT'])]). relacion([sujeto(['The', motivation, of, professionals, to]), verbo([involve]), complemento([partners, in, the, rehabilitation, process, assisted, with, the, introduction, of, 'PACT', in, practice])]). relacion([sujeto(['Implications', for, 'Rehabilitation', 'The', integration, of, a, new, treatment, method, that, reaches, beyond, the, boundaries, of, one, group, of, professionals, needs, to, be, facilitated, by]), verbo([providing]), complemento([time, to, all, team, members, involved, to, discuss, and, think, through, the, consequences, of, that, approach, for, clinical, decision, making, within, the, care, trajectory, of, a, client, and, 'his/her', significant, other])]). relacion([sujeto(['As', part, of, the, 'Healthy,', 'Hunger-Free', 'Kids', 'Act,', 'snacks,', and, desserts, sold, in, 'K-12', schools, as, of, the, 2014, -, 2015, school, year, are]), verbo([required]), complemento([to, meet, the, &, 'quot;Smart', 'Snacks"', nutritional, guidelines])]). relacion([sujeto(['Many', districts, across, the, country]), verbo([have]), complemento([made, headway, in, complying, with, the, 'Smart', 'Snack', 'guidelines,', though, gaps, remain])]). relacion([sujeto(['The', recent, growth, of, 'ROMP', activities]), verbo([has]), complemento([created, an, ethical, and, regulatory, gray, zone, with, significant, implications, for, the, oversight, of, human, subjects, research])]). relacion([sujeto(['Our', study, revealed, that, 'IRB', members, are, unclear, or, divided, on, the, central, questions, at, stake, in, the, current, policy, debate, over, ethical, oversight, of, 'ROMP:', 'IRB', members, struggle, to, make, a, clear, distinction, between, clinical, research, and, medical, practice, 'improvement,', lack, consensus, on, when, 'ROMP']), verbo([requires]), complemento(['IRB', review, and, 'oversight,', and, are, uncertain, about, what, constitutes, incremental, risk, when, patients, are, randomized, to, different, 'treatments,', any, of, which, may, be, offered, in, usual, care])]). relacion([sujeto(['They', characterized, the, central, challenge, as, a, balancing, 'act,', 'between,', on, the, one, 'hand,', making, information, fully, transparent, to, patients, and]), verbo([providing]), complemento([adequate, 'oversight,', and, on, the, other, 'hand,', avoiding, a, chilling, effect, on, the, research, process, or, harming, the, 'physician-patient', relationship])]). relacion([sujeto(['Evidence-based', guidance, that, supports, 'IRB', members, in]), verbo([providing]), complemento([adequate, and, effective, oversight, of, 'ROMP', without, impeding, the, research, process, or, harming, the, 'physician-patient', relationship, is, necessary, to, realize, the, full, benefits, of, the, learning, health, system])]). relacion([sujeto(['Macroautophagy', '(', hereafter, referred, to, as, 'autophagy)', is, a, housekeeping, process, constitutively]), verbo([executed]), complemento([at, basal, level, in, all, cells, to, promote, cellular, homeostasis, by, regulating, organelle, and, protein, turnover])]). relacion([sujeto(['However,', autophagy, deregulation]), verbo([caused]), complemento([by, several, stress, 'factors,', such, as, 'hypoxia,', is, prevalent, in, many, cancers])]). relacion([sujeto(['It', is, now, well, established, that, autophagy, can]), verbo([act]), complemento([as, tumor, suppressor, or, tumor, promoter, depending, on, tumor, 'type,', 'stage,', and, genetic, context])]). relacion([sujeto(['In', developed, 'tumors,', autophagy]), verbo([promotes]), complemento([the, survival, of, cancer, cells, and, therefore, operates, as, a, cell, resistance, mechanism])]). relacion([sujeto(['Emerging', evidence, point, to, the, prominent, role, of, autophagy, in, disabling, the, antitumor, immune, response, by, multiple, overlapping, mechanisms]), verbo([leading]), complemento([to, tumor, escape, from, immune, cell, attack, mediated, by, both, natural, killer, cells, and, cytotoxic, 'T-lymphocytes'])]). relacion([sujeto(['Such', a, role]), verbo([has]), complemento([inspired, significant, interest, in, applying, 'anti-autophagy', therapies, as, an, entirely, new, approach, to, overcome, tumor, escape, from, immune, 'surveillance,', which, constitutes, so, far, a, major, challenge, in, developing, more, effective, cancer, immunotherapies])]). relacion([sujeto(['In', this, 'review,', we, will, summarize, recent]), verbo([reports]), complemento([describing, how, tumor, 'cells,', by, activating, 'autophagy,', manage, to, hijack, the, immune, system])]). relacion([sujeto(['In', keeping, with, 'this,', we, strongly, believe, that, autophagy, represents, an, attractive, future, therapeutic]), verbo([target]), complemento([to, develop, innovative, and, effective, cancer, immunotherapeutic, approaches])]). relacion([sujeto(['It']), verbo([has]), complemento([been, demonstrated, that, microRNAs, '(', miRNAs, or, 'miRs)', can, act, as, prognostic, and, diagnostic, 'markers,', and, potential, therapeutic, targets])]). relacion([sujeto(['miR-95-3p']), verbo([has]), complemento([been, reported, to, be, downregulated, in, osteosarcoma, 'tissues,', but, its, potential, as, a, serum, biomarker, has, not, been, assessed, in, human, osteosarcoma])]). relacion([sujeto(['Compared', to, healthy, 'controls,', the, expression, levels, of, 'miR-95-3p', in, serum, of, osteosarcoma, patients, were, significantly]), verbo([decreased]), complemento(['(', 'P < 0'])]). relacion([sujeto(['Our', findings]), verbo([suggested]), complemento([that, 'down-expression', of, serum, 'miR-95-3p', might, be, associated, with, poor, prognosis, of, osteosarcoma, 'patients,', suggesting, that, decreased, expression, of, serum, 'miR-95-3p', may, serve, as, a, valuable, 'diagnostic/prognostic', marker, for, osteosarcoma, patients])]). relacion([sujeto(['An', atomistic, understanding, of, the, feldspar, structure, and, its, interaction, with, water, is, therefore, 'desirable,', not, least, because, feldspar]), verbo([has]), complemento([been, shown, to, dominate, ice, nucleation, by, mineral, dusts, in, 'Earth\'s', atmosphere])]). relacion([sujeto(['The', complexity, of, the, 'ice/feldspar', interface, arising, from, the, numerous, chemical, motifs]), verbo([expressed]), complemento([on, the, surface, makes, it, a, challenging, system])]). relacion([sujeto(['Here', we]), verbo([report]), complemento([a, comprehensive, study, of, this, challenging, system, with, ab, initio, density, functional, theory, calculations])]). relacion([sujeto(['We', 'do,', 'however,', identify, contact, layer, structures, of, water, that]), verbo([induce]), complemento(['ice-like', ordering, in, the, second, overlayer])]). relacion([sujeto(['This']), verbo([suggests]), complemento([that, even, substrates, without, an, apparent, match, with, the, ice, structure, may, still, act, as, excellent, ice, nucleating, agents])]). relacion([sujeto(['Plant', growth]), verbo([promoting]), complemento([rhizobacteria, produce, chemical, compounds, with, different, benefits, for, the, plant])]). relacion([sujeto(['Among', 'them,', 'HCN', is]), verbo([recognized]), complemento([as, a, biocontrol, 'agent,', based, on, its, ascribed, toxicity, against, plant, pathogens])]). relacion([sujeto(['Based', on, several, past, studies, questioning, the, validity, of, this, 'hypothesis,', we]), verbo([have]), complemento(['re-addressed', the, issue, by, designing, a, new, set, of, in, vitro, 'experiments,', to, test, if, 'HCN-producing', rhizobacteria, could, inhibit, the, growth, of, phytopathogens])]). relacion([sujeto(['We', developed, a, new, 'concept,', in, which, 'HCN', does, not]), verbo([act]), complemento([as, a, biocontrol, 'agent,', but, rather, is, involved, in, geochemical, processes, in, the, substrate, '(', e])]). relacion([sujeto([',', chelation, of, 'metals),', indirectly]), verbo([increasing]), complemento([the, availability, of, phosphate])]). relacion([sujeto(['Since', this, scenario, can, be, important, for, the, pioneer, plants, living, in, oligotrophic, alpine, 'environments,', we, inoculated, 'HCN', producing, bacteria, into, sterile, mineral, sand, together, with, germinating, plants, and, showed, that, the, growth, of, the, pioneer, plant, 'French', sorrel, was]), verbo([increased]), complemento([on, 'granite-based', substrate])]). relacion([sujeto(['To', support, our, 'concept,', we, used, 'KCN', and, mineral, sand, and, showed, that, mineral, mobilization, and, phosphate]), verbo([release]), complemento([could, be, caused, by, cyanide, in, vitro])]). relacion([sujeto(['We', propose, that, in, oligotrophic, alpine, 'environments,', and, possibly, 'elsewhere,', the, main, contribution, of, 'HCN', is, in, the, sequestration, of, metals, and, the, consequential, indirect]), verbo([increase]), complemento([of, nutrient, 'availability,', which, is, beneficial, for, the, rhizobacteria, and, their, plant, hosts])]). relacion([sujeto(['Avatars', are, digital, 'self-representations,', which, enable, individuals, to]), verbo([interact]), complemento([with, each, other, in, 'computer-based', virtual, environments])]). relacion([sujeto(['In', this, narrative, 'review,', we, examine, the, psychotherapeutic, applications, of, avatars, that]), verbo([have]), complemento([been, investigated, and, trialed, to, date])]). relacion([sujeto(['Across', these, 'applications,', avatars, appeared, to, serve, several, functions, conducive, to, treatment, engagement, by, '(', 1, ')', facilitating, the, development, of, a, virtual, therapeutic, 'alliance;', '(', 2, ')', reducing, communication, 'barriers;', '(', 3, ')']), verbo([promoting]), complemento(['treatment-seeking', through, 'anonymity;', '(', 4, ')', promoting, expression, and, exploration, of, client, 'identity;', and, '(', 5, ')', enabling, therapists, to, control, and, manipulate, treatment, stimuli])]). relacion([sujeto(['The', 'contextual,', 'ecological,', and, organizational, factors, are, those]), verbo([associated]), complemento([with, 'RHCs,', not, hospitals])]). relacion([sujeto(['We', cannot, infer, how, the, variability, in, hospital, practices, in, 'RHC', service, areas, may]), verbo([have]), complemento([contributed, to, the, disparities, in, admissions])]). relacion([sujeto(['The', '{', 'Cu(NO₃)(H₂O)}(HTae)(4,4\'-Bpy)', '(', 'H₂Tae', =, 1, ',', 1, ',', 2, ',', 2, -, 'tetraacetylethane,', 4, ',', 4, '\'', -, 'Bpy', =, 4, ',', 4, '\'', -, 'Dipyridyl)', 1, 'D', coordination, polymer]), verbo([has]), complemento([been, obtained, by, slow, evaporation])]). relacion([sujeto(['These', open, metal, sites, could]), verbo([act]), complemento([as, 'Lewis', acid, active, sites, in, several, heterogeneous, catalytic, reactions])]). relacion([sujeto(['The', dehydrated, 'compound,', 'CuHTaeBpy_HT,']), verbo([has]), complemento([been, tested, as, a, heterogeneous, recoverable, catalyst, for, 'Knoevenagel', condensation, reactions])]). relacion([sujeto(['The', catalyst, suffers, a, partial]), verbo([loss]), complemento([of, activity, when, reusing, 'it,', but, can, be, reused, at, least, four, times])]). relacion([sujeto(['Malodorous', pollution]), verbo([has]), complemento([previously, been, associated, with, aggravated, physical, and, psychological, 'health,', and, in, persons, affected, by, a, 'trauma,', an, 'incidence-related', odour, can, act, as, a, traumatic, reminder])]). relacion([sujeto(['Participants', in, the, high, odour, score, group, '(', 'n=233)']), verbo([reported]), complemento([more, 'SHC', and, 'PTSS', than, those, in, the, low, odour, score, group, '(', 'n=253),', before, and, even, after, the, pollution, was, eliminated])]). relacion([sujeto(['The', data, presented, in, this, article]), verbo([provide]), complemento([evidence, that, 'enkephalin,', and, not, 'NPY,', could, act, upon, the, majority, of, 'IGL', neurons])]). relacion([sujeto(['Moreover,', we, investigated, the, type, of, opioid, receptor]), verbo([activated]), complemento([by, enkephalin, and, showed, that, the, 'μ-receptor', is, functionally, predominant, in, the, 'IGL'])]). relacion([sujeto(['The', application, of, 'met-enkephalin', not, only, robustly, hyperpolarized, 'IGL', neurons, '(', both, putatively, 'NPY-synthesizing', and, putatively, enkephalinergic, 'neurons),', but, it, also, was, able, to]), verbo([inhibit]), complemento(['GABAergic', and, glutamatergic, synaptic, transmission])]). relacion([sujeto(['Based', on, this, and, previous, 'studies,', we, hypothesize, that, 'IGL', enkephalinergic, neurons, may]), verbo([act]), complemento([as, powerful, interneurons, that, inhibit, themselves, and, 'NPY-synthesizing', 'neurons,', also, in, the, contralaterally, located, 'IGL'])]). relacion([sujeto(['In', the, present, 'work,', the]), verbo([release]), complemento([mechanisms, of, active, pharmaceutical, ingredients, '(', 'APIs)', enclosed, in, 'self-pore', forming, regenerated, cellulose, '(', 'RC)', 'two-piece', hard, shell, capsules, are, described])]). relacion([sujeto(['Drug']), verbo([release]), complemento([characteristics, from, 'RC', capsules, were, evaluated, using, potassium, 'chloride,', diphenhydramine, 'hydrochloride,', tramadol, 'hydrochloride,', 'niacinamide,', acetaminophen, and, ketoprofen, as, model, 'APIs'])]). relacion([sujeto(['The', 'RC', capsules]), verbo([act]), complemento([as, a, barrier, coated, reservoir, device, that, releases, the, enclosed, 'API', at, a, zero, order, release, rate])]). relacion([sujeto(['When', comparing, all, the, 'API\'s']), verbo([release]), complemento([behavior, from, 'RC', 'capsules,', a, 'power-law', relationship, was, observed, between, their, 'zero-order', release, rates, and, their, respective, aqueous, solubilities])]). relacion([sujeto(['Osmotic', as, well, as, diffusive, mechanisms, are]), verbo([involved]), complemento([in, the, release, of, the, enclosed, 'API'])]). relacion([sujeto(['The', osmotic, 'mechanism\'s', contribution, to, zero, order]), verbo([release]), complemento([rate, increases, as, the, aqueous, solubility, of, the, tested, 'APIs', inside, the, capsule, increases])]). relacion([sujeto(['The', osmotic]), verbo([mediated]), complemento([flux, and, the, apparent, diffusivity, of, the, 'APIs', through, the, capsule, wall, is, a, competitive, process, and, the, osmotic, mediated, flux, of, the, enclosed, 'API', begins, to, override, its, diffusivity, through, the, capsule, wall, as, the, 'API', solubility, increases])]). relacion([sujeto(['Botanical-mediated', synthesis, of, nanomaterials, is, currently, emerging, as, a, cheap, and, 'eco-friendly', 'nanotechnology,', since, it, does, not]), verbo([involve]), complemento([the, use, of, toxic, chemicals])]). relacion([sujeto(['Light', and, confocal, laser, scanning, microscopic, observation, evidenced, that, the, 'MPPE-AuNPs', effectively]), verbo([inhibited]), complemento([the, biofilm, of, 'E'])]). relacion([sujeto(['Cytotoxicity', studies, demonstrated, that, 'MPPE-AuNPs', were, effective, in]), verbo([inhibiting]), complemento([the, viability, of, human, 'A549', lung, cancer, cells, at, higher, concentrations, of, 100, &, 'nbsp;μg ml(-1)'])]). relacion([sujeto(['This', study, concludes, that, 'MPPE-AuNPs', are, 'non-toxic,', 'eco-friendly', and]), verbo([act]), complemento([as, potential, biomaterial, for, biomedical, applications])]). relacion([sujeto(['Alongside', uric, acid, 'formation,']), verbo([increased]), complemento([xanthine, oxidase, activity, also, results, in, the, formation, of, oxidative, free, radicals, and, superoxide, particles])]). relacion([sujeto(['Allopurinol,', a, competitive, xanthine, oxidase, 'inhibitor,', in, addition, to, reducing, serum, uric, acid, 'levels,', can]), verbo([act]), complemento([as, a, free, radical, scavenger])]). relacion([sujeto(['Although', traditionally, used, for, the, management, of, 'gout,', there]), verbo([has]), complemento([been, renewed, interest, in, the, role, of, allopurinol, in, the, management, of, cardiovascular, disease])]). relacion([sujeto(['A', number, of, small, clinical, studies]), verbo([have]), complemento([shown, a, beneficial, effect, of, allopurinol, in, reducing, 'ischemia-reperfusion', injury, in, the, setting, of, bypass, surgery, and, coronary, angioplasty])]). relacion([sujeto(['Whilst', this, cheap, and, readily, available, pharmacological, option, may, offer, a, very, cost, effective, therapeutic, 'option,', 'large-scale', prospective, studies, are]), verbo([required]), complemento([to, better, delineate, its, role, in, reducing, hard, clinical, 'end-points'])]). relacion([sujeto(['We', hypothesized, that, whereas, the, vast, majority, of, women, ultimately]), verbo([have]), complemento([no, imaging, explanation, for, their, breast, 'pain,', a, small, percentage, of, patients, may, have, a, correlative, imaging, finding, and, confirm, the, current, 'American', 'College', of, 'Radiology', 'Appropriateness', 'Criteria', recommendations])]). relacion([sujeto(['No', imaging, correlates, were]), verbo([found]), complemento([in, women, with, 'noncyclical,', nonfocal, 'pain,', supporting, the, 'American', 'College', of, 'Radiology', 'Appropriateness', 'Criteria', ratings])]). relacion([sujeto(['There', was, no, radiological, imaging]), verbo([finding]), complemento([to, explain, the, etiology, of, mastalgia, in, most, women])]). relacion([sujeto(['Therapeutic', strategies, that]), verbo([act]), complemento([by, eliciting, and, enhancing, antitumor, immunity, have, been, clinically, validated, as, an, effective, treatment, modality, but, may, benefit, from, the, induction, of, both, cell, death, and, immune, activation, as, primary, stimuli])]). relacion([sujeto(['Using', our, 'AdRGD-PG', adenovector, 'platform,', we, show, here, for, the, first, time, that, in, situ, gene, transfer, of, p19Arf, and, 'interferon-β', '(', 'IFNβ)', in, the, 'LLC1', mouse, model, of, lung, carcinoma]), verbo([acts]), complemento([as, an, immunotherapy])]). relacion([sujeto(['Although', p19Arf, is, sufficient, to]), verbo([induce]), complemento([cell, 'death,', only, its, pairing, with, 'IFNβ', significantly, induced, markers, of, immunogenic, cell, death])]). relacion([sujeto(['In', situ, gene, therapy, with, 'IFNβ,', either, alone, or, in, combination, with, 'p19Arf,', could, retard, tumor, 'progression,', but, only, the, combined, treatment, was]), verbo([associated]), complemento([with, a, protective, immune, response])]). relacion([sujeto(['Specifically', in, the, case, of, combined, intratumoral, gene, 'transfer,', we, identified, 167, differentially]), verbo([expressed]), complemento([genes, when, using, microarray, to, evaluate, tumors, that, were, treated, in, vivo, and, confirmed, the, activation, of, 'CCL3,', 'CXCL3,', 'IL1α,', 'IL1β,', 'CD274,', and, 'OSM,', involved, in, immune, response, and, chemotaxis])]). relacion([sujeto(['In', 'all,', in, situ, gene, transfer, with, p19Arf, and, 'IFNβ']), verbo([acts]), complemento([as, an, immunotherapy, involving, recruitment, of, 'neutrophils,', a, desirable, but, previously, untested, 'outcome,', and, this, approach, may, be, allied, with, 'chemotherapy,', thus, providing, significant, antitumor, activity, and, warranting, further, development, for, the, treatment, of, lung, carcinoma])]). relacion([sujeto(['Thirty-two', percent, '(', 579, /, 1815, ')', of, practice, group, leaders]), verbo([responded]), complemento([to, the, survey, and, of, 'these,', 73, '%', '(', 432, /, 579, ')', answered, 'FMLA', 'questions,', with, 15, '%', of, those, '(', 64, /, 432, ')', answering, affirmatively, that, a, radiologist, in, their, practice, had, taken, 'FMLA', leave])]). relacion([sujeto(['Canonical', growth, factors]), verbo([act]), complemento([indirectly, via, 'receptor-mediated', signal, transduction, pathways])]). relacion([sujeto(['Here,', we]), verbo([report]), complemento([on, an, autonomous, pathway, in, which, a, growth, factor, is, 'internalized,', has, its, localization, regulated, by, 'phosphorylation,', and, ultimately, uses, intrinsic, catalytic, activity, to, effect, epigenetic, change])]). relacion([sujeto(['Angiogenin', '(', 'ANG),', a, secreted, vertebrate, 'ribonuclease,', is, known, to]), verbo([promote]), complemento([cell, 'proliferation,', leading, to, neovascularization, as, well, as, neuroprotection, in, mammals])]). relacion([sujeto(['Upon', entering, 'cells,', 'ANG', encounters, the, cytosolic, ribonuclease, inhibitor, 'protein,', which]), verbo([binds]), complemento([with, femtomolar, affinity])]). relacion([sujeto(['We']), verbo([find]), complemento([that, protein, kinase, 'C', and, 'cyclin-dependent', kinase, phosphorylate, 'ANG,', enabling, 'ANG', to, evade, its, inhibitor, and, enter, the, nucleus])]). relacion([sujeto(['After', migrating, to, the, 'nucleolus,', 'ANG', cleaves, 'promoter-associated', 'RNA,', which]), verbo([prevents]), complemento([the, recruitment, of, the, nucleolar, remodeling, complex, to, the, ribosomal, 'DNA', promoter])]). relacion([sujeto(['The', ensuing, derepression, of, rDNA, transcription]), verbo([promotes]), complemento([cell, proliferation])]). relacion([sujeto(['The', biochemical, basis, for, this, unprecedented, mechanism, of, signal, transduction]), verbo([suggests]), complemento([new, modalities, for, the, treatment, of, cancers, and, neurological, disorders])]). relacion([sujeto(['Lipids', are, structural, components, of, 'cells,']), verbo([act]), complemento([as, a, source, of, 'energy,', and, function, as, signaling, mediators])]). relacion([sujeto(['Alterations', in, lipid, metabolism, are]), verbo([involved]), complemento([in, the, onset, and, progression, of, a, variety, of, 'diseases,', including, metabolic, syndrome, and, cancer])]). relacion([sujeto(['Because', of, 'this,', interest, in, 'lipidomics,', the, comprehensive, characterization, of, the, lipidome, by, mass, 'spectrometry,']), verbo([has]), complemento([intensified, in, recent, years])]). relacion([sujeto(['However,', obtaining, a, truly, complete, overview, of, all, lipids, in, a, sample]), verbo([has]), complemento([remained, very, challenging, due, to, their, enormous, structural, diversity])]). relacion([sujeto(['Here,', we]), verbo([provide]), complemento([an, overview, of, the, collection, of, analytical, approaches, used, to, study, various, lipid, 'classes,', emphasizing, innovations, in, sample, preparation, and, liquid, 'chromatography-mass', spectrometry, '(', 'LC-MS)'])]). relacion([sujeto(['Additionally,', we]), verbo([provide]), complemento([practical, suggestions, for, increasing, the, coverage, of, the, lipidome])]). relacion([sujeto(['Cognitive', behavioral, therapy, '(', 'CBT)', and, acceptance, and, commitment, therapy, '(', 'ACT)']), verbo([have]), complemento([both, garnered, empirical, support, for, the, effective, treatment, of, social, anxiety, disorder])]). relacion([sujeto(['Public', speaking, avoidance, was]), verbo([found]), complemento([to, be, a, robust, moderator, of, outcome, 'measures,', with, more, avoidant, individuals, generally, benefitting, more, from, 'CBT', than, 'ACT', by, 12, -, month, 'follow-up'])]). relacion([sujeto(['In', 'contrast,', 'clinician-rated', social, avoidance, was, not]), verbo([found]), complemento([to, be, a, significant, moderator, of, any, outcome, measure])]). relacion([sujeto(['Results', were]), verbo([found]), complemento([only, at, 12, -, month, 'follow-up'])]). relacion([sujeto(['Findings', inform, personalized, 'medicine,']), verbo([suggesting]), complemento([that, social, avoidance, measured, behaviorally, via, a, public, speaking, task, may, be, a, more, robust, factor, in, treatment, prescription, compared, to, 'clinician-rated', social, avoidance])]). relacion([sujeto(['For', 'example,', exposure, to, 'thin,', 'human-like', sculptures, by, the, artist, 'Alberto', 'Giacometti']), verbo([has]), complemento([been, found, to, promote, healthy, snack, choices, at, a, vending, machine])]). relacion([sujeto(['Whether', 'health-', or, 'weight-related', processes, drive, such, effects]), verbo([has]), complemento([not, yet, been, determined])]). relacion([sujeto(['However,', a, detailed, understanding, of, the, 'content-related', drivers, of, environmental, 'cues\'', effects]), verbo([provides]), complemento([the, first, indications, regarding, a, 'cue\'s', possible, use])]). relacion([sujeto(['Overall,', these, studies]), verbo([suggest]), complemento([that, the, thin, sculptures, are, primarily, 'weight-related', cues, and, particularly, helpful, for, restrained, eaters])]). relacion([sujeto(['Environmental', 'weight-control', cues, such, as, the, 'Giacometti', sculptures, could]), verbo([act]), complemento([as, a, counterforce, to, our, obesogenic, environment, and, help, restrained, eaters, pursue, their, 'weight-control', goal])]). relacion([sujeto(['Bt', toxins, ingested, by, insect, pests, can]), verbo([bind]), complemento([to, midgut, receptors, and, cause, 'death,', although, several, steps, in, this, process, remain, unclear])]). relacion([sujeto(['Multiple', 'Bt', toxin, receptors]), verbo([have]), complemento([been, identified, in, 'Lepidoptera,', including, a, 'cadherin-like', protein, '(', 'CaLP),', which, is, central, to, several, models, explaining, 'Bt', 'toxins\'', mode, of, action])]). relacion([sujeto(['Mutations', in, the, 'Plutella', xylostella, 'ATP-dependent']), verbo([binding]), complemento([cassette, transporter, 'C2', '(', 'Px-abcc2),', rather, than, 'CaLP,', are, genetically, linked, with, 'Bt', 'Cry1Ac', resistance])]). relacion([sujeto(['Here', we]), verbo([expressed]), complemento(['Px-abcc2', in, 'Drosophila', and, performed, larval, bioassays, to, determine, whether, this, protein, acts, as, an, effective, 'Bt', receptor])]). relacion([sujeto(['Cry1Ac', had, no, effect, on, larvae]), verbo([expressing]), complemento(['Px-abcc2', in, salivary, 'glands,', yet, larvae, expressing, 'Px-abcc2', in, the, midgut, were, highly, susceptible, to, both, 'Cry1Ac', protoxin, and, trypsin, activated, toxin])]). relacion([sujeto(['Furthermore,', the, 'CaLP', orthologue]), verbo([has]), complemento([been, lost, from, the, 'Drosophila', 'genome,', making, this, a, useful, system, for, investigating, the, role, of, 'CaLP', peptides, from, 'Manduca', sexta, '(', 'CR12-MPED),', which, are, known, to, act, as, 'Bt', synergists, in, larval, feeding, assays])]). relacion([sujeto(['Drosophila', larvae]), verbo([expressing]), complemento(['Px-ABCC2', in, the, midgut, were, fed, 'LD50', concentrations, of, 'Cry1Ac', toxin, or, 'protoxin,', plus, purified, 'CR12-MPED', cloned, from, 'M'])]). relacion([sujeto([&, 'nbsp;sexta', 'CR12-MPED', protein]), verbo([acted]), complemento([synergistically, with, 'Cry1Ac', protoxin, and, activated, toxin, significantly, more, effectively, than, the, 'P'])]). relacion([sujeto(['However,', the, effects, of, 'ACT', treatment, on, gastric, cancer]), verbo([have]), complemento([little, been, known])]). relacion([sujeto(['However,', gastric, cancer, cells, receiving, 'ACT', were, sensitive, to, 'TRAIL-triggered', apoptotic, response, by]), verbo([enhancing]), complemento(['Caspases', 'cleavage,', due, to, elevation, of, decoy, receptor, 1, and, 2, '(', 'DcR1', and, 'DcR2)', dependent, on, p53])]). relacion([sujeto(['Bcl-2', family, members, of, 'Bcl-2', and, 'Mcl-1,', belonging, to, 'anti-apoptosis,', were, 'decreased,', whereas, 'Bad', and, 'Bak,', as, 'pro-apoptotic', 'members,', were]), verbo([increased]), complemento([for, 'ACT', and, 'TRAIL', combined, treatment])]). relacion([sujeto(['Additionally,', the, mouse, xenograft, model]), verbo([suggested]), complemento([that, 'ACT', and, 'TRAIL', in, combination, markedly, inhibited, gastric, cancer, growth, in, comparison, to, 'ACT', or, 'TRAIL', monotherapy, without, toxicity])]). relacion([sujeto(['The', present, study, revealed, a, dramatically, therapeutic, strategy, for]), verbo([promoting]), complemento(['TRAIL-induced', 'anti-cancer', effects, on, gastric, cancer, cells, via, 'ACT', combination])]). relacion([sujeto(['The', 'US', 'Food', and, 'Drug', 'Administration', '(', 'FDA)', 'Amendments', 'Act', of, 2007, granted, the, 'FDA', new, authorities, to]), verbo([enhance]), complemento([drug, safety, by, requiring, application, holders, to, submit, a, proposed, 'Risk', 'Evaluation', and, 'Mitigation', 'Strategy', '(', 'REMS)'])]). relacion([sujeto(['A', 'REMS', is, a]), verbo([required]), complemento([risk, management, plan, that, uses, tools, beyond, the, package, insert])]). relacion([sujeto(['An', implementation, system, is]), verbo([required]), complemento([for, an, 'REMS', that, includes, the, 'ETASUs'])]). relacion([sujeto(['With', approximately, eight, years, of, experience, with, 'REMS', 'programs,', many, health, care, settings]), verbo([have]), complemento([created, systems, to, manage, 'REMS', and, also, to, integrate, 'REMS', into, their, practice, settings])]). relacion([sujeto(['At', the, same, 'time,', there, are, issues]), verbo([associated]), complemento([with, the, development, and, implementation, of, 'REMS'])]). relacion([sujeto(['This', review, attempts, to, share, our, 'company\'s', experience, with, the, 'REMS', 'program,', and, to]), verbo([provide]), complemento([updates, on, 'FDA\'s', efforts, to, improve, 'REMS', 'communication,', to, standardize, 'REMS', 'process,', to, reduce, 'REMS', program, burdens, and, to, build, a, common, 'REMS', platform])]). relacion([sujeto(['Our', model]), verbo([suggests]), complemento([that, if, 'LAFA', estimates, were, actually, 'consumed,', reference, individuals, would, have, lost, '~1-4kg/y', from, 1971, -, 1980, '(', an, accumulated, loss, of, '~12', to, '~36kg),', and, gained, '~3-7kg/y', from, 1988, -, 2010, '(', an, accumulated, gain, of, '~42', to, '~98kg)'])]). relacion([sujeto(['The', 'USDA', 'LAFA', data]), verbo([provided]), complemento(['inconsistent,', divergent, estimates, of, per, capita, caloric, consumption, over, its, 39, -, year, history])]). relacion([sujeto(['The', 'large,', variable, misestimation]), verbo([suggests]), complemento([that, the, 'USDA', 'LAFA', per, capita, caloric, intake, estimates, lack, validity, and, should, not, be, used, to, inform, public, policy])]). relacion([sujeto([absolute, 10, &, 'nbsp;year', risk, was, presented, as, a, thermometer, and]), verbo([expressed]), complemento([as, a, 'percentage,', natural, frequency, and, '\'', heart, 'age\''])]). relacion([sujeto(['We', 'tape-recorded', and]), verbo([transcribed]), complemento([the, interviews, and, focus, groups, and, analysed, them, using, thematic, analysis])]). relacion([sujeto(['An', 'interactive,', user, 'friendly,', goal, setting, based, lifestyle, website, can]), verbo([act]), complemento([as, a, trigger, to, initiate, moderate, lifestyle, 'changes,', regardless, of, concerns, about, risk, scores])]). relacion([sujeto(['Global', constitutionalism, is, a, way, of, looking, at, the, 'world,', at, global, rules, and, how, they, are, 'made,', as, if, there, was, a, global, 'constitution,', empowering, global, institutions, to]), verbo([act]), complemento([as, a, global, 'government,', setting, rules, which, bind, all, states, and, people])]). relacion([sujeto(['This', essay, employs, global, constitutionalism, to, examine, how, and, why, global, health, 'governance,', as, currently, 'structured,']), verbo([has]), complemento([struggled, to, advance, the, right, to, 'health,', a, fundamental, human, rights, obligation, enshrined, in, the, 'International', 'Covenant', on, 'Economic,', 'Social', and, 'Cultural', 'Rights'])]). relacion([sujeto(['Improving', assessment, guidance, and, feedback, for, students]), verbo([has]), complemento([become, an, international, priority, within, higher, education])]). relacion([sujeto(['Podcasts']), verbo([have]), complemento([been, proposed, as, a, tool, for, enhancing, 'teaching,', learning, and, assessment])]). relacion([sujeto(['To', consider, how, these, podcasts, shaped, beliefs, about, their, ability, to, successfully, engage, 'with,', and]), verbo([act]), complemento(['on,', assessment, guidance, and, feedback, 'Design', 'Exploratory', qualitative, study])]). relacion([sujeto(['Purposive', sampling, was, utilised, to]), verbo([recruit]), complemento([participants, of, different, 'ages,', 'gender,', levels, of, 'self-assessed', information, technology, skills, and, levels, of, academic, achievement])]). relacion([sujeto(['Further', analysis, revealed, that, 'Self-Efficacy', 'Theory']), verbo([provided]), complemento([deeper, theoretical, insights, into, how, the, 'content,', structure, and, delivery, of, podcasts, can, be, shaped, to, promote, more, successful, engagement, with, assessment, guidance, and, feedback, from, students])]). relacion([sujeto(['The', 'structured,', logical, approach, of, assessment, guidance, podcasts, appeared, to, strengthen, 'self-efficacy', by]), verbo([providing]), complemento([readily, accessible, support, and, by, helping, students, convert, intentions, into, action])]). relacion([sujeto(['Students', with, high, 'self-efficacy', in, relation, to, tasks]), verbo([associated]), complemento([with, assessment, were, more, likely, to, engage, with, 'feedback,', whereas, those, with, low, 'self-efficacy', tended, to, overlook, opportunities, to, access, feedback, due, to, feelings, of, helplessness, and, futility])]). relacion([sujeto(['Adopting', 'well-structured', podcasts, as, an, educational, 'tool,', based, around, the, four, major, sources, of, information, '(', performance, 'accomplishments,', vicarious, 'experience,', social, 'persuasion,', and, physiological, and, emotional, 'states),']), verbo([has]), complemento([potential, to, promote, self, efficacy, for, 'individuals,', as, well, as, groups, of, 'students,', in, terms, of, assessment, guidance, and, feedback])]). relacion([sujeto(['In', the, past, 'years,', 'multi-atlas', 'patch-based', label, fusion, methods]), verbo([have]), complemento([achieved, a, great, success, in, medical, image, segmentation])]). relacion([sujeto(['To', address, this, 'issue,', we, propose, a, novel, label, fusion, framework, to, seek, for, the, suitable, label, fusion, weights, by, progressively, constructing, a, dynamic, dictionary, in, a, 'layer-by-layer', 'manner,', where, the, intermediate, dictionaries]), verbo([act]), complemento([as, a, sequence, of, guidance, to, steer, the, transition, of, '(', 'patch)', representation, coefficients, from, the, image, domain, to, the, label, domain])]). relacion([sujeto(['IL-18', can]), verbo([act]), complemento([as, a, cofactor, for, 'Th2', cell, development, and, 'IgE', production, and, also, plays, an, important, role, in, the, differentiation, of, 'Th1', cells])]). relacion([sujeto(['Recent', work, identified, an, 'IL-18', association, with, the, pathogenesis, of, 'asthma,', wherein]), verbo([increased]), complemento(['IL-18', expression, was, found, in, the, serum, of, patients])]). relacion([sujeto(['Furthermore,', 'IL-18', polymorphisms, with, susceptibility, to, asthma, were, 'reported,']), verbo([suggesting]), complemento([that, 'IL-18', may, be, therapeutically, relevant, to, asthma])]). relacion([sujeto(['On', 'average,', 'boy\'s', 'H-I', behaviours, showed, temporal, stability, while, for, girls, 'H-I']), verbo([decreased]), complemento([over, time, with, a, slower, rate, of, decrease, with, age])]). relacion([sujeto(['Neither', the, shape, nor, rate, of, change, of, 'H-I', problems, were]), verbo([associated]), complemento([with, language, status])]). relacion([sujeto(['Parental', hostility, was]), verbo([associated]), complemento([with, the, rate, of, growth, only, for, boys, with, typical, language])]). relacion([sujeto(['The', findings, indicate, that, having, a, language, difficulty, at, school, entry, is]), verbo([associated]), complemento([with, persistently, higher, levels, of, 'H-I', problems, across, childhood, and, moderates, the, rate, of, their, growth, in, some, circumstances])]). relacion([sujeto(['The', direct, oral, anticoagulants, '(', 'DOACs)']), verbo([have]), complemento([emerged, as, a, good, alternative, for, the, treatment, of, thromboembolic, 'diseases,', and, their, use, in, clinical, practice, is, increasing, rapidly])]). relacion([sujeto(['The', 'DOACs']), verbo([act]), complemento([by, blocking, the, activity, of, one, single, step, in, the, coagulation, cascade])]). relacion([sujeto(['These', drugs]), verbo([act]), complemento([downstream, in, the, common, pathway, of, the, coagulation, cascade, by, directly, antagonising, the, action, of, thrombin, or, factor, 'Xa'])]). relacion([sujeto(['The', scanning, model, for, eukaryotic, mRNA, translation, initiation, states, that, the, small, ribosomal, 'subunit,', along, with, initiation, 'factors,']), verbo([binds]), complemento([at, the, cap, structure, at, the, 5, '\'', end, of, the, mRNA, and, scans, the, 5, '\'', untranslated, region, '(', 5, '\'', 'UTR)', until, an, initiation, codon, is, found])]). relacion([sujeto(['However,', under, conditions, that, impair, canonical, 'cap-dependent', 'translation,', the, synthesis, of, some, proteins, is, kept, by, alternative, mechanisms, that, are]), verbo([required]), complemento([for, cell, survival, and, stress, recovery])]). relacion([sujeto(['Recent', evidence, uncovered, a, distinct, mechanism, through, which, mRNAs, containing, 'N', '(', 6, ')', -, methyladenosine, '(', 'm(6)A)', residues, in, their, 5, '\'', 'UTR', directly]), verbo([bind]), complemento([eukaryotic, initiation, factor, 3, '(', 'eIF3)', and, the, 40, 'S', ribosomal, subunit, in, order, to, initiate, translation, in, the, absence, of, the, 'cap-binding', proteins])]). relacion([sujeto(['This', review, focuses, on, the, important, role, of, 'cap-independent', translation, mechanisms, in, human, cells, and, how, these, alternative, mechanisms, can, either]), verbo([act]), complemento([individually, or, cooperate, with, other, 'cis-acting', 'RNA', regulons, to, orchestrate, specific, translational, responses, triggered, upon, several, cellular, stress, 'states,', and, diseases, such, as, cancer])]). relacion([sujeto(['Elucidation', of, these, 'non-canonical', mechanisms]), verbo([reveals]), complemento([the, complexity, of, translational, control, and, points, out, their, potential, as, prospective, novel, therapeutic, targets])]). relacion([sujeto(['Cysteine-rich', peptides, 'LUREs', secreted, from, the, synergid, cells, on, either, side, of, the, egg, cell]), verbo([act]), complemento([as, ovular, attractants, of, pollen, tubes])]). relacion([sujeto(['We', recently]), verbo([reported]), complemento([that, ovular, 4, -, 'O-methyl-glucuronosyl', arabinogalactan, 'AMOR', induces, competency, of, the, pollen, tube, to, respond, to, ovular, attractant, 'LURE', peptides, in, 'Torenia', fournieri])]). relacion([sujeto(['However,', critical, and, 'non-critical', structures, in, the, disaccharide]), verbo([have]), complemento([not, been, dissected, deeply])]). relacion([sujeto(['Herein,', we]), verbo([report]), complemento([the, synthesis, of, new, 'AMOR', analogs, and, the, 'structure-activity', relationships, '(', 'SAR)', for, 'AMOR', activity, in, the, presence, of, these, synthesized, analogs])]). relacion([sujeto(['This', study, represents, the, first, 'SAR', study, of, sugar, molecule]), verbo([involved]), complemento([in, plant, 'reproduction,', which, opens, a, way, for, modification, of, the, molecule, without, loss, of, activity])]). relacion([sujeto(['Successful', male, gametogenesis]), verbo([involves]), complemento([orchestration, of, sequential, gene, regulation, for, somatic, differentiation, in, 'pre-meiotic', anthers])]). relacion([sujeto(['We']), verbo([report]), complemento([here, the, cloning, of, 'Male', 'Sterile23', '(', 'Ms23),', encoding, an, 'anther-specific', predicted, basic, 'helix-loop-helix', '(', 'bHLH)', transcription, factor, required, for, tapetal, 'differentiation;', transcripts, localize, initially, to, the, precursor, secondary, parietal, cells, then, predominantly, to, daughter, tapetal, cells])]). relacion([sujeto(['RNA-seq', and, proteomics, data, together, with, yeast, 'two-hybrid', assays]), verbo([suggest]), complemento([that, 'MS23', along, with, 'MS32,', 'bHLH122,', and, bHLH51, act, sequentially, as, either, 'homo-', or, heterodimers, to, choreograph, tapetal, development])]). relacion([sujeto(['In', 'contrast,', 'MS32', is, constitutive, and, independently]), verbo([regulated]), complemento([and, is, required, later, than, 'MS23', in, tapetal, differentiation])]). relacion([sujeto(['Aspirin']), verbo([has]), complemento([the, potential, to, acetylate, other, 'amino-acid', 'side-chains,', leading, to, the, possibility, that, 'aspirin-mediated', lysine, acetylation, could, explain, some, of, its, 'as-yet', unexplained, drug, actions, or, 'side-effects'])]). relacion([sujeto(['Although', aspirin, amplifies, endogenous, acetylation, signals, at, the, majority, of, detectable, endogenous, 'sites,', cells, tolerate, aspirin]), verbo([mediated]), complemento([acetylation, very, well, unless, cellular, deacetylases, are, inhibited])]). relacion([sujeto(['This', work, shows, that, while, aspirin]), verbo([has]), complemento([enormous, potential, to, alter, protein, 'function,', in, the, majority, of, cases, 'aspirin-mediated', acetylations, do, not, accumulate, to, levels, likely, to, elicit, biological, effects])]). relacion([sujeto(['These', findings, are, consistent, with, an, emerging, model, for, cellular, acetylation, whereby, stoichiometry, correlates, with, biological, 'relevance,', and, deacetylases]), verbo([act]), complemento([to, minimize, the, biological, consequences, 'non-specific', chemical, acetylations])]). relacion([sujeto(['Over', 60, papers]), verbo([have]), complemento([been, published, covering, key, challenges, reported, by, 'participants:', financial, 'problems,', loneliness, and, social, 'isolation,', 'unemployment,', poor, physical, 'health,', uncontrolled, symptoms, of, mental, 'illness,', and, lack, of, 'stable,', suitable, housing])]). relacion([sujeto(['The', rate, of, cardiometabolic, disease, was, well, above, the, general, population, 'rate,', and]), verbo([associated]), complemento([risk, factors, were, present, from, a, very, young, age])]). relacion([sujeto(['Meeting', these, challenges]), verbo([has]), complemento([the, potential, to, reduce, costs, to, government, and, 'society,', as, well, as, promote, recovery])]). relacion([sujeto(['The', canonical, view, about, the, effect, of, thyroid, hormones, '(', 'THs)', on, thermogenesis, assumes, that, the, hypothalamus]), verbo([acts]), complemento([merely, as, a, modulator, of, the, sympathetic, outflow, on, brown, adipose, tissue, '(', 'BAT)'])]). relacion([sujeto(['Recent', data]), verbo([have]), complemento([challenged, that, vision, by, demonstrating, that, 'THs', act, on, the, ventromedial, nucleus, of, the, hypothalamus, '(', 'VMH)', to, inhibit, 'AMP-activated', protein, kinase, '(', 'AMPK),', which, regulates, the, thermogenic, program, in, 'BAT,', leading, to, increased, thermogenesis, and, weight, loss])]). relacion([sujeto(['Current', data]), verbo([have]), complemento([shown, that, in, addition, to, activation, of, brown, 'fat,', the, browning, of, white, adipose, tissue, '(', 'WAT)', might, be, also, an, important, thermogenic, mechanism])]). relacion([sujeto(['Here,', we, show, that, 3, ',', 3, '\'', ',', 5, ',', 5, '\'', tetraiodothyroxyne, '(', 'T4)-induced', hyperthyroidism]), verbo([promotes]), complemento([a, marked, browning, of, 'WAT'])]). relacion([sujeto(['Overall,', these, data, indicate, that, 'THs']), verbo([induce]), complemento([browning, of, 'WAT', and, that, this, mechanism, is, mediated, via, the, central, effects, of, 'THs', on, energy, balance])]). relacion([sujeto(['Total', nominal, 'US', health, care, spending]), verbo([increased]), complemento([5.8, &, 'nbsp;percent', and, reached, '$3'])]). relacion([sujeto(['On', a, per, person, 'basis,', spending, on, health, care]), verbo([increased]), complemento([5.0, &, 'nbsp;percent,', reaching, '$9,990'])]). relacion([sujeto(['The', system, accounts, here, for, both, matched, and, unmatched, unknown, uncertainties, that, can]), verbo([act]), complemento([as, plant, as, well, as, input, effectiveness, failures, or, damages])]). relacion([sujeto(['It', is, capable, of, adjusting, a, sudden, change, in, system, dynamics, without, depending, on, high, adaptation]), verbo([gains]), complemento([and, can, satisfy, exponential, parameter, error, convergence, under, certain, conditions, in, the, presence, of, structured, matched, and, unmatched, uncertainties, as, well])]). relacion([sujeto(['It']), verbo([provides]), complemento([a, 'closed-form', control, solution])]). relacion([sujeto(['Cascade', regression, is, a, popular, face, alignment, 'approach,', and, it]), verbo([has]), complemento([achieved, good, performances, on, the, wild, databases])]). relacion([sujeto(['Also,', the, occlusion, levels, of, the, landmarks]), verbo([act]), complemento([as, adaptive, weights, on, the, 'shape-indexed', features, to, decrease, the, noise, on, the, 'shape-indexed', features])]). relacion([sujeto(['At', the, same, 'time,', an, exemplarbased, shape, prior, is, designed, to]), verbo([suppress]), complemento([the, influence, of, local, image, corruption])]). relacion([sujeto(['Histone', deacetylases, '(', 'HDACs)(2)', play, important, roles, in, the, epigenetic, regulation, of, gene, expression, in, cells, and, are, emerging, therapeutic]), verbo([targets]), complemento([for, treating, a, wide, range, of, diseases])]). relacion([sujeto(['HDAC', inhibitors, '(', 'HDACi)(3)', that]), verbo([act]), complemento([on, multiple, 'HDAC', enzymes, have, been, used, clinically, to, treat, a, number, of, solid, and, hematological, malignancies])]). relacion([sujeto(['HDACi', are, currently, being, studied, also, for, their, efficacy, in, 'non-malignant', 'diseases,', including, pathologic, bone, 'loss,', but, this]), verbo([has]), complemento([necessitated, a, better, understanding, of, the, roles, of, individual, 'HDAC', 'enzymes,', particularly, the, eleven, 'zinc-containing', isozymes])]). relacion([sujeto(['Isozyme-specific', 'HDACi', promise, to]), verbo([have]), complemento([greater, efficacy, and, reduced, side, 'effects,', as, required, for, treating, chronic, disease, over, extended, periods, of, time])]). relacion([sujeto(['Past', studies, show, that, mu, and, delta, opioid, receptors]), verbo([regulate]), complemento([behaviors, associated, with, social, ascension, or, defeat])]). relacion([sujeto(['Opioids', also]), verbo([act]), complemento([at, kappa, 'receptors,', with, dynorphin, binding, with, the, highest, 'affinity;', 'however,', the, role, of, these, opioids, in, social, behavior, has, not, been, well, studied])]). relacion([sujeto(['We', observed, flocks, of, male, starlings, during, the, breeding, season, and, ran, quantitative, 'real-time', polymerase, chain, reaction, '(', 'qPCR)', to, measure, expression, of, kappa, opioid, receptors, '(', 'OPRK1)', and, prodynorphin, '(', 'PDYN)', in, brain, regions]), verbo([involved]), complemento([in, social, behavior, and, motivation, '(', ventral, tegmental, area, '[', 'VTA],', medial, preoptic, nucleus, '[', 'mPOA])', and, vocal, behavior, '(', 'Area', 'X)'])]). relacion([sujeto(['OPRK1', expression, in, 'VTA', correlated, negatively, with, 'sexual/agonistic', 'behaviors,', consistent, with, past, studies, showing, kappa, receptors, in, 'VTA', to]), verbo([inhibit]), complemento([sociosexual, behaviors])]). relacion([sujeto(['Distinct', patterns, of, 'OPRK1', and, 'PDYN', expression, in, 'VTA,', 'mPOA,', and, 'Area', 'X', related, to, gonad, 'volume,']), verbo([suggesting]), complemento([that, breeding, condition, may, modify, '(', or, be, modified, 'by)', 'OPRK1', and, 'PDYN', expression])]). relacion([sujeto(['The', immune, system, plays, an, important, role, in]), verbo([enhancing]), complemento([an, 'individual\'s', ability, to, survive, in, a, world, inhabited, by, pathogens, and, parasites])]). relacion([sujeto(['The', innate, immune, system, is]), verbo([regulated]), complemento([by, processes, encoded, in, an, 'individual\'s', 'genome,', providing, an, avenue, for, selection, to, act, on, this, 'system,', as, well, as, the, phenotypic, relationships, generated, between, this, system, and, other, traits, of, interest])]). relacion([sujeto(['testosterone)']), verbo([have]), complemento([been, reported, often, in, the, 'literature,', these, relationships, are, complex, and, may, differ, under, varying, environmental, conditions])]). relacion([sujeto(['This', review, revealed, a, very, limited, number, of, repeatability, 'estimates,', with, a, large, range, '(', 0.0, -, 0.9, ')', ;, estimates, were, exclusively, from, livestock, that]), verbo([have]), complemento([undergone, strong, artificial, selection])]). relacion([sujeto(['This', observation, of, the, present, literature]), verbo([suggests]), complemento([more, work, is, needed, in, 'non-domesticated', and, 'free-living', animals, to, begin, to, understand, the, underlying, genetic, contribution, of, innate, immune, function, to, phenotypic, correlations, of, interest, '(', e])]). relacion([sujeto(['The', main, goal, of, the, drug, therapy, in, 'MS', is, to, take, control, of, the, inflammation, which]), verbo([leads]), complemento([to, the, destruction, of, myelin, and, axons, in, nerve, cell, and, thus, prevent, and, stop, the, progression, of, the, disease])]). relacion([sujeto(['Fingolimod', '(', 'FTY720)', is, an, orally, active, immunomodulatory, drug, that]), verbo([has]), complemento([been, used, for, the, treatment, of, 'relapsing-remitting', multiple, sclerosis])]). relacion([sujeto(['It', is, a, 'sphingosine-1-phosphate', receptor, modulator, which]), verbo([prevents]), complemento([lymphocytes, from, contributing, to, an, autoimmune, reaction, by, inhibiting, egress, of, lymphocytes, them, from, lymph, nodes])]). relacion([sujeto(['In', this, 'study,', we]), verbo([have]), complemento([computer, 'designed,', synthesized, and, characterized, two, novel, derivatives, of, 'FTY720,', 'F1-12h', and, 'F2-9,', and, have, determined, their, underlying, mechanism, of, their, beneficial, effect, in, 'SH-SY5Y,', 'SK-N-SH,', and, 'U-118', 'MG', cell, lines])]). relacion([sujeto(['Then,', we]), verbo([have]), complemento([determined, their, effect, on, 'MS-', and, 'GPCR-related', gene, expression, profiles, using, custom, arrays, along, with, 'FTY720', treatment, at, 'non-toxic', doses, '(', 'EC10)'])]). relacion([sujeto(['It', was]), verbo([found]), complemento([that, both, derivatives, significantly, activate, 'CRE', and, increase, cAMP, concentration, in, all, three, cell, 'lines,', indicating, that, they, activate, cAMP, pathway, through, cell, surface, receptors, as, 'FTY720', does])]). relacion([sujeto(['Furthermore,', 'F1-12h', and, 'F2-9']), verbo([modulate]), complemento([the, expression, of, the, pathway, related, genes, that, are, important, in, inflammatory, 'signaling,', cAMP, signaling, 'pathway,', cell, migration, as, well, as, diverse, receptor, and, transcription, factors])]). relacion([sujeto(['Expression', of, the, genes]), verbo([involved]), complemento([in, myelination, was, also, increased, by, the, treatment, with, 'F1-12h', and, 'F2-9'])]). relacion([sujeto(['In', 'summary,', our, data, demonstrate, that, the, two, novel, 'FTY720', derivatives]), verbo([act]), complemento([as, 'anti-inflammatory', ultimately, by, influencing, the, gene, expression, via, the, cAMP, and, downstream, transcription, factor, 'CRE', pathway])]). relacion([sujeto([1, ')', ',', to, be]), verbo([associated]), complemento([with, high, 'ComMed', quality])]). relacion([sujeto(['Hospitals\'', small, 'bed-size,', 'physician/non-profit', 'ownership,', 'critical-access', 'type,', absent, 'ED', 'services,', and, 100, -, 299, 'HCAHPS', completed, surveys, were, more, likely, to, be]), verbo([associated]), complemento([with, high, 'ComMed', quality])]). relacion([sujeto(['One', of, the, first, national, studies]), verbo([found]), complemento([significant, variations, in, 'ComMed', quality, across, 'U'])]). relacion([sujeto(['With', this, baseline, 'data,', hospital, providers, and, policymakers, can, 'design,', 'implement,', and, evaluate, service, programs, with, pharmacists, and, 'HIT', to]), verbo([enhance]), complemento(['ComMed', quality, in, the, future, delivery, of, 'patient-centered', care])]). relacion([sujeto(['The', study, was, carried, out, to, address, a, method, for, separation, of, terrestrial, and, marine, biogenic, silica, '(', 'BSi)', in, estuaries, based, on, 'BSi', compositions, and, 'δ(13)C', values, in, 'BSi']), verbo([associated]), complemento([organic, matter, '(', 'δ(13)CBSi)'])]). relacion([sujeto(['Thus,', the, variation, of, 'δ(13)C', within, 'BSi', organic, matter, can]), verbo([provide]), complemento([terrestrial, source, information, on, the, biogeochemistry, of, silicon, in, estuaries, and, the, adjacent, shelf])]). relacion([sujeto(['The', 'δ(13)CBSi', combination, could, potentially]), verbo([act]), complemento([as, an, efficient, tool, to, study, environmental, change, in, coastal, areas, on, decadal, 'time-scales', since, this, index, may, respond, to, variable, terrestrial, fluxes, from, 'land,', as, well, as, to, changed, phytoplankton, assemblages, in, the, coastal, ocean])]). relacion([sujeto(['Critical', care, patients, are, at]), verbo([increased]), complemento([risk, of, infection])]). relacion([sujeto(['Near-patient', surfaces]), verbo([act]), complemento([as, reservoirs, of, microbial, 'soil,', which, may, contain, pathogens])]). relacion([sujeto(['Ten', 1, &, 'nbsp;h', covert, audits, of, 'hand-touch', frequency, of, these, sites, were, performed, in, order, to]), verbo([provide]), complemento([an, average, 'hand-touch', 'count,', which, was, modelled, against, soil, levels, obtained, from, microbiological, screening])]). relacion([sujeto(['Seven', of, 10, staphylococci, were]), verbo([found]), complemento([in, conjunction, with, gross, contamination, of, a, specific, site, '(', 'P=0'])]). relacion([sujeto(['We', suspected, that, customary, placement, of, alcohol, gel, containers, on, bed, tables, may]), verbo([have]), complemento([reduced, microbiological, yield])]). relacion([sujeto(['Surface', bioburden, at, 'near-patient', sites, in, 'ICU', is]), verbo([associated]), complemento([with, 'hand-contact', frequencies, by, staff, and, visitors])]). relacion([sujeto(['This', supports, the, need, for]), verbo([targeted]), complemento([hygienic, cleaning, in, a, 'high-risk', healthcare, environment])]). relacion([sujeto(['Few']), verbo([reports]), complemento([showed, its, effect, on, anxiety, behaviors])]). relacion([sujeto(['It']), verbo([increased]), complemento([the, time, that, mice, visited, open, arms, and, light, box, area, in, elevated, plus, maze, and, 'light-dark', box, tests, after, acute, and, chronic, 'YYO', exposures])]). relacion([sujeto(['It']), verbo([decreased]), complemento([the, dopamine, '(', 'DA)', concentration, in, the, striatum, and, increased, the, 5, -, hydroxytryptamine, '(', 5, -, 'HT)', concentration, in, the, hippocampus, of, the, male, mice])]). relacion([sujeto(['Moreover,', it]), verbo([decreased]), complemento([the, ratio, of, 5, -, 'HIAA/5-HT', in, the, hippocampus])]). relacion([sujeto(['YYO', and, its, major, constituent, benzyl, benzoate, might]), verbo([act]), complemento([on, the, 5, -, 'HTnergic', and, 'DAnergic', pathways])]). relacion([sujeto(['For', this, 'reason,', the, 'US', 'FDA']), verbo([has]), complemento([promulgated, the, 'Produce', 'Rule,', mandating, the, testing, of, irrigation, water, sources, for, many, farms])]). relacion([sujeto(['The', rule]), verbo([requires]), complemento([the, collection, and, analysis, of, at, least, 20, water, samples, over, two, to, four, years, to, adequately, evaluate, the, quality, of, water, intended, for, produce, irrigation])]). relacion([sujeto(['We']), verbo([found]), complemento([that, weather, conditions, of, a, specific, year, may, strongly, affect, the, evaluation, of, microbial, quality, and, that, the, 'long-term', assessment, of, microbial, water, quality, may, be, quite, different, from, the, evaluation, based, on, 'short-term', observations])]). relacion([sujeto(['Two', of, 'these,']), verbo([increased]), complemento([resource, availability, and, enemy, 'release,', may, act, in, concert, to, increase, exotic, success, in, plant, communities, '(', 'Resource-Enemy', 'Release', 'Hypothesis,', 'R-ERH)'])]). relacion([sujeto(['Second,', fertilization]), verbo([increased]), complemento([foliar, damage, on, native, 'species,', but, not, exotic, species])]). relacion([sujeto(['When', both, conditions, are, 'fulfilled,', 'R-ERH', predicts, that]), verbo([increasing]), complemento([resource, availability, will, increase, exotic, abundance, only, in, the, presence, of, enemies])]). relacion([sujeto(['Our', results, fully, supported, this, prediction, for, vertebrate, 'herbivores:', fertilization]), verbo([increased]), complemento([exotic, cover, only, in, communities, exposed, to, vertebrate, herbivores])]). relacion([sujeto(['Recent', studies]), verbo([suggest]), complemento([that, head, 'lice,', as, is, the, case, of, body, 'lice,', can, act, as, a, vector, for, 'louse-borne', diseases])]). relacion([sujeto(['Here,', we]), verbo([report]), complemento([the, results, of, the, first, molecular, screening, of, 'pygmies\'', head, lice, in, the, 'Republic', of, 'Congo', for, seven, pathogens, and, an, analysis, of, lice, mitochondrial, clades])]). relacion([sujeto(['We', identified, the, presence, of, a, dangerous, human, 'pathogen,', 'Borrelia', 'recurrentis,', the, causative, agent, of, relapsing, 'fever,', in, ten, clade, 'A', head, 'lice,', which, was, not]), verbo([reported]), complemento([in, the, 'Republic', of, 'Congo,', and, 'B'])]). relacion([sujeto(['This', study, is, also, the, first, to]), verbo([report]), complemento([the, presence, of, 'DNAs', of, 'B'])]). relacion([sujeto(['In', vitro, prediction, of, the, probable, rapid, emergence, of, resistance, to, a, drug, in, tumors, could]), verbo([act]), complemento([to, winnow, out, potential, candidates, for, further, costly, development])]). relacion([sujeto(['We']), verbo([have]), complemento([developed, a, microfluidic, device, consisting, of, '∼500', hexagonal, microcompartments, that, provides, a, complex, ecology, with, wide, ranges, of, drug, and, nutrient, gradients, and, local, populations])]). relacion([sujeto(['This', ecology, of, a, fragmented, metapopulation]), verbo([induced]), complemento([the, drug, resistance, in, stage, 'IV', 'U87', glioblastoma, cells, to, doxorubicin, in, 7, d])]). relacion([sujeto(['Exome', and, transcriptome, sequencing, of, the, resistant, cells, identified, mutations, and, differentially]), verbo([expressed]), complemento([genes])]). relacion([sujeto(['Specifically,', we, identified, '(', 'i)', a, 'frame-shift', insertion, in, the, 'filamin-A', 'gene,', which]), verbo([regulates]), complemento([the, influx, and, efflux, of, topoisomerase, 'II', 'poisons;', '(', 'ii)', the, overexpression, of, 'aldo-keto', reductase, 'enzymes,', which, convert, doxorubicin, into, 'doxorubicinol;', and, '(', 'iii)', activation, of, 'NF-κB', via, alterations, in, the, 'nucleotide-binding', oligomerization, domain, '(', 'NOD)-like', receptor, signaling, pathway, from, mutations, in, three, genes, '(', 'CARD6,', 'NSD1,', and, 'NLRP13)', and, the, overexpression, of, inflammatory, cytokines])]). relacion([sujeto(['Our', findings]), verbo([suggest]), complemento(['that,', given, the, rapid, evolution, of, resistance, and, the, focused, 'response,', this, technology, could, act, as, a, rapid, screening, modality, for, genetic, aberrations, leading, to, resistance, to, chemotherapy, as, well, as, counter, selection, of, drugs, unlikely, to, be, successful, ultimately])]). relacion([sujeto([',', by, fluorination, or, 'methylation,', we]), verbo([have]), complemento([recently, designed, and, biosynthesized, biologically, more, active, 'TSR', analogs])]). relacion([sujeto(['Using', these, analogs, as, chemical, 'probes,', we, uncovered, an, unusual, indirect, mechanism, of, 'TSR-type', 'thiopeptides,', which, are, able, to]), verbo([act]), complemento([against, intracellular, pathogens, through, host, autophagy, induction, in, addition, to, direct, targeting, of, bacterial, ribosome])]). relacion([sujeto(['Herein,', we]), verbo([report]), complemento([the, accumulation, of, 6, '\'', -, 'fluoro-7\',', 8, '\'', -, 'epoxy-TSR,', a, key, intermediate, in, the, preparation, of, the, analog, 6, '\'', -, 'fluoro-TSR'])]). relacion([sujeto(['This', unexpected]), verbo([finding]), complemento([led, to, unveiling, of, the, 'TSR', maturation, 'process,', which, involves, an, unusual, dual, activity, of, 'TsrI,', an, 'α/β-hydrolase', fold, 'protein,', for, cascade, 'C-N', bond, cleavage, and, formation, during, 'side-ring', system, construction])]). relacion([sujeto(['These', two, functions, of, 'TsrI', rely, on, the, same, catalytic, 'triad,', 'Ser72-His200-Asp191,', which, first]), verbo([mediates]), complemento([endopeptidyl, hydrolysis, that, occurs, selectively, between, the, residues, 'Met-1', and, 'Ile1', for, removal, of, the, leader, peptide, and, then, triggers, epoxide, ring, opening, for, closure, of, the, 'QA-containing', 'side-ring', system, in, a, 'regio-', and, 'stereo-specific', manner])]). relacion([sujeto(['The', former, reaction, likely]), verbo([requires]), complemento([the, formation, of, an, 'acyl-Ser72', enzyme, 'intermediate;', in, 'contrast,', the, latter, is, independent, of, 'Ser72'])]). relacion([sujeto(['Rho', 'GTPases,', including, the, 'Rho,', 'Cdc42,', 'Rac,', and, 'ROP', 'subfamilies,']), verbo([act]), complemento([as, pivotal, signaling, switches, in, various, growth, and, developmental, processes])]). relacion([sujeto(['In', a, mutant, screen, for, phenotypic, enhancers, of, transgenic, 'Arabidopsis', plants]), verbo([expressing]), complemento([a, constitutively, active, form, of, 'ROP2', '(', designated, 'CA1-1),', we, identified, 'RNA', polymerase, 'II', '(', 'Pol', 'II)', 'C-terminal', domain, '(', 'CTD)', 'phosphatase-like', 1, '(', 'CPL1)', as, a, transcriptional, regulator, of, 'ROP2', signaling])]). relacion([sujeto(['We', show, that, 'ROP2', activation]), verbo([inhibits]), complemento(['CPL1', activity, by, promoting, its, 'degradation,', leading, to, an, increase, in, 'CTD', 'Ser5', and, 'Ser2', phosphorylation])]). relacion([sujeto(['We', also, observed, similar, modulation, of, 'CTD', phosphorylation, by, yeast, 'Cdc42', 'GTPase', and]), verbo([enhanced]), complemento([degradation, of, the, yeast, 'CTD', phosphatase, 'Fcp1', by, activated, 'ROP2', signaling])]). relacion([sujeto(['Taken', 'together,', our, results]), verbo([suggest]), complemento([that, modulation, of, the, 'Pol', 'II', 'CTD', code, by, 'Rho', 'GTPase', signaling, represents, an, evolutionarily, conserved, mechanism, in, both, unicellular, and, multicellular, eukaryotes])]). relacion([sujeto(['At', chemical, 'synapses,', presynaptic, action, potentials, '(', 'APs)']), verbo([activate]), complemento(['voltage-gated', calcium, 'channels,', allowing, calcium, to, enter, and, trigger, neurotransmitter, release])]). relacion([sujeto(['The', 'duration,', peak, 'amplitude,', and, shape, of, the, 'AP', falling, phase, alter, calcium, 'entry,', which, can, affect, neurotransmitter]), verbo([release]), complemento([significantly])]). relacion([sujeto(['We', hypothesized, that, presynaptic, afterpotentials, should, alter, neurotransmitter]), verbo([release]), complemento([by, affecting, the, electrical, driving, force, for, calcium, entry, and, calcium, channel, gating])]). relacion([sujeto(['Surprisingly,', presynaptic, afterpotentials, after, 'AP', stimuli, did, not, alter, calcium, channel, responses, or, neurotransmitter]), verbo([release]), complemento([appreciably])]). relacion([sujeto(['We', show, that, the, 'AP', repolarization, time, course]), verbo([causes]), complemento(['afterpotential-induced', changes, in, calcium, driving, force, and, changes, in, calcium, channel, gating, to, effectively, cancel, each, other, out])]). relacion([sujeto(['This', 'mechanism,', in, which, electrical, driving, force, is, balanced, by, channel, 'gating,']), verbo([prevents]), complemento([changes, in, calcium, influx, from, occurring, at, the, end, of, the, 'AP', and, therefore, acts, to, stabilize, synaptic, transmission])]). relacion([sujeto(['In', 'addition,', this, mechanism, can]), verbo([act]), complemento([to, stabilize, neurotransmitter, release, when, the, presynaptic, resting, potential, changes])]). relacion([sujeto(['We', show, that, the, 'AP', falling, phase]), verbo([causes]), complemento(['afterpotential-induced', changes, in, electrical, driving, force, and, calcium, channel, gating, to, cancel, each, other, out])]). relacion([sujeto(['This', mechanism]), verbo([regulates]), complemento([calcium, entry, at, the, end, of, 'APs', and, therefore, stabilizes, synaptic, transmission])]). relacion([sujeto(['The', patient, should, therefore, take, these, drugs, for, the, rest, of, 'his/her', 'life,', which, can]), verbo([cause]), complemento(['drug-resistance', and, adverse, effects])]). relacion([sujeto(['Therefore,', more, durable, therapeutic, strategies, should, be, 'considered,', such, as, a, stable, gene, therapy, to, protect, the]), verbo([target]), complemento(['T', cells, against, 'HIV-1', infection])]). relacion([sujeto(['These', mechanisms, attack, different, forms, of, the, viral, 'genome,', the, 'RNA', and, 'DNA,', 'respectively,', but, both, mechanisms]), verbo([act]), complemento([in, a, strictly, 'sequence-specific', manner])]). relacion([sujeto(['Such', therapy, failure, can, be]), verbo([prevented]), complemento([by, the, design, of, a, combinatorial, 'RNAi', attack, on, the, virus, and, this, gene, therapy, is, currently, being, tested, in, a, preclinical, humanized, mouse, model])]). relacion([sujeto(['Recent', 'CRISPR-Cas', studies, also, document, robust, virus, 'inhibition,', but]), verbo([suggest]), complemento([a, novel, viral, escape, route, that, is, induced, by, the, cellular, nonhomologous, end, joining, 'DNA', repair, 'pathway,', which, is, activated, by, 'CRISPR-Cas-induced', 'DNA', breaks])]). relacion([sujeto(['Mitochondrial', oxidative, damage]), verbo([has]), complemento([long, been, known, to, contribute, to, damage, in, conditions, such, as, 'ischaemia-reperfusion', '(', 'IR)', injury, in, heart, attack])]). relacion([sujeto(['Over', the, past, 'years,', we]), verbo([have]), complemento([developed, a, series, of, 'mitochondria-targeted', compounds, designed, to, ameliorate, or, determine, how, this, damage, occurs])]). relacion([sujeto(['I', will, outline, some, of, this, 'work,', from, 'MitoQ', to, the, 'mitochondria-targeted', 'S-nitrosating', 'agent,', called, 'MitoSNO,', that, we, showed, was, effective, in]), verbo([preventing]), complemento([reactive, oxygen, species, '(', 'ROS)', formation, in, 'IR', injury, with, therapeutic, implications])]). relacion([sujeto(['In', 'addition,', the, protection, by, this, compound]), verbo([suggested]), complemento([that, 'ROS', production, in, 'IR', injury, was, mainly, coming, from, complex, 'I'])]). relacion([sujeto(['This']), verbo([led]), complemento([us, to, investigate, the, mechanism, of, the, 'ROS', production, and, using, a, metabolomic, 'approach,', we, found, that, the, 'ROS', production, in, 'IR', injury, came, from, the, accumulation, of, succinate, during, ischaemia, that, then, drove, mitochondrial, 'ROS', production, by, reverse, electron, transport, at, complex, 'I', during, reperfusion])]). relacion([sujeto(['This', surprising, mechanism]), verbo([led]), complemento([us, to, develop, further, new, therapeutic, approaches, to, have, an, impact, on, the, damage, that, mitochondrial, 'ROS', do, in, pathology, and, also, to, explore, how, mitochondrial, 'ROS', can, act, as, redox, signals])]). relacion([sujeto(['I', will, discuss, how, these, approaches]), verbo([have]), complemento([led, to, a, better, understanding, of, mitochondrial, oxidative, damage, in, pathology, and, also, to, the, development, of, new, therapeutic, strategies])]). relacion([sujeto(['PM10', particles, may]), verbo([act]), complemento([as, carriers, of, adsorbed, allergens, possibly, transporting, them, to, the, lower, respiratory, 'tract,', where, they, could, trigger, allergic, reactions])]). relacion([sujeto(['So', far, the, allergen, content, of, 'PM10']), verbo([has]), complemento([been, studied, by, means, of, enzyme, linked, immunosorbent, assays, '(', 'ELISAs)', and, scanning, electron, microscopy])]). relacion([sujeto(['In', conjunction, with, clinical, 'data,', the, presented, method, offers, the, opportunity, to, test, in, future, experiments, whether, allergic, reactions, to, birch, pollen, antigens, are]), verbo([associated]), complemento([with, the, 'Bet', v, 1, allergen, content, of, 'PM10', particles, &, 'gt;0'])]). relacion([sujeto(['Studies']), verbo([have]), complemento([reported, that, the, presence, of, a, third, party, observer, '(', 'TPO)', during, neuropsychological, assessments, negatively, affects, the, test, performance, of, the, examinee])]). relacion([sujeto(['A', sample, of, college, students, was]), verbo([recruited]), complemento(['(', 'n = 318)', and, then, 80, participants, were, selected, to, represent, the, high, and, low, trait, anxiety, groups])]). relacion([sujeto(['These', findings]), verbo([provide]), complemento([support, for, the, hypotheses, of, 'ACT', regarding, the, relation, between, observer, presence, and, poorer, performance, on, neuropsychological, 'tests,', with, individuals, with, higher, trait, anxiety, showing, greater, negative, effects])]). relacion([sujeto(['Self-regulation', constrains, the, expression, of, 'prejudice,', but, when, 'self-regulation', 'falters,', the, immediate, environment, can]), verbo([act]), complemento([as, an, external, source, of, prejudice, regulation])]). relacion([sujeto(['Across', four, studies, we]), verbo([found]), complemento([support, for, this, complementary, model, of, prejudice, regulation])]). relacion([sujeto(['Finally,', in, 'Study', 4, 'self-regulatory', fatigue]), verbo([increased]), complemento([prejudice, when, social, pressure, was, weak, but, not, when, it, was, strong])]). relacion([sujeto(['To', further]), verbo([enhance]), complemento([the, intensity, of, deep, tumor, drug, delivery, and, integrate, a, combined, 'therapy,', we, herein, report, on, a, 'core-shell', nanocarrier, that, could, simultaneously, overcome, the, double, barriers, of, the, extracellular, matrix, '(', 'ECM)', and, multiple, layers, of, tumor, cells, '(', 'MLTC)'])]). relacion([sujeto(['The', swelling, of, the, core, resulted, in, the, rapid]), verbo([release]), complemento([of, chemotherapeutics, to, kill, 'autophagy-inhibited', cells])]). relacion([sujeto(['After', leaving, the, dead, 'cells,', the, shrinking, core, could]), verbo([act]), complemento([on, neighboring, cells, that, were, closer, to, the, center, of, the, tumor])]). relacion([sujeto(['DNA', metabolization, of, thiated, prodrugs, can]), verbo([lead]), complemento([to, cell, death, upon, exposure, to, a, low, dose, of, 'UVA', light])]). relacion([sujeto(['In', this, 'work,', we]), verbo([have]), complemento([combined, femtosecond, broadband, transient, absorption, experiments, with, 'state-of-the-art', molecular, simulations, to, provide, mechanistic, insights, for, the, ultrafast, and, efficient, population, of, the, 'triplet-state', in, the, 'UVA-activated', pyrimidine, anticancer, 'drug:', 4, -, thiothymine])]). relacion([sujeto(['The', triplet, state, is, thought, to]), verbo([act]), complemento([as, a, precursor, to, the, 'DNA', lesions, and, the, reactive, oxygen, species, responsible, for, 4, -, thiothymine, photocytotoxicity])]). relacion([sujeto(['The', 'electronic-structure', and, mechanistic, results, presented, in, this, contribution]), verbo([reveal]), complemento([key, molecular, design, criteria, that, can, assist, in, developing, alternative, chemotherapeutic, agents, that, may, overcome, some, of, the, primary, deficiencies, of, classical, photosensitizers])]). relacion([sujeto(['Thrombomodulin', '(', 'TM)']), verbo([modulates]), complemento([the, activation, of, protein, 'C', and, coagulation])]). relacion([sujeto(['Additionally,', 'TM']), verbo([regulates]), complemento([monocyte, migration, and, inflammation])]). relacion([sujeto(['First,', we]), verbo([found]), complemento([that, 'TM', was, increased, when, 'THP-1', cells, were, treated, with, 'phorbol-12-myristate-13-acetate', '(', 'PMA)'])]). relacion([sujeto(['Overexpression', of, 'TM']), verbo([enhanced]), complemento([the, macrophage, 'markers,', 'CD14', and, 'CD68', expression, in, 'PMA-induced', 'THP-1'])]). relacion([sujeto(['TM', siRNA, depressed, the, 'PMA-induced']), verbo([increase]), complemento([of, 'p21(Cip1/WAF1)', via, 'ERK1/2-NF-kB', p65, signaling])]). relacion([sujeto(['TM']), verbo([regulated]), complemento([cytoskeletal, reorganization, via, its, interaction, with, 'paxillin,', 'cofilin,', 'LIMK1,', and, 'PYK2'])]). relacion([sujeto(['In', 'addition,', 'PMA-induced', 'p21(Cip1/WAF1)', 'expression,', 'CD14-positive', cell, labeling, intensity, and, 'ERK1/2', phosphorylation, were, markedly]), verbo([inhibited]), complemento([when, protein, kinase, 'C-δ', '(', 'PKCδ)', was, knocked, down])]). relacion([sujeto(['We', identified, that, 'TM', directly]), verbo([interacts]), complemento([with, 'PKCδ'])]). relacion([sujeto(['PKCδ', was, highly]), verbo([expressed]), complemento([in, human, atherosclerotic, arteries, and, colocalized, with, 'TM', in, 'CD68-positive', infiltrated, macrophages, of, 'plaques,', indicating, that, the, coordination, between, 'TM', and, 'PKCδ', in, macrophages, participated, in, atherogenesis])]). relacion([sujeto(['TM', may]), verbo([act]), complemento([as, a, scaffold, for, 'PKCδ', 'docking,', which, keeps, 'PKCδ', in, the, region, close, to, the, monocyte, membrane, to, promote, the, activation, of, 'ERK1/2'])]). relacion([sujeto(['Taken', 'together,', our, findings]), verbo([suggest]), complemento([that, 'TM-PKCδ', interaction, may, contribute, to, cardiovascular, disorders, by, affecting, monocye, 'differentiation,', which, may, develop, future, therapeutic, applications])]). relacion([sujeto(['Mesenchymal', stem, cells, '(', 'MSCs)', are, speculated, to]), verbo([act]), complemento([at, 'macrophage-injury', interfaces, to, mediate, efficient, repair])]). relacion([sujeto(['MSCs']), verbo([promoted]), complemento([macrophage, 'differentiation,', enhanced, respiratory, burst, and, potentiated, microbicidal, responses, in, naïve, macrophages, '(', 'Mφ)'])]). relacion([sujeto(['Functional', attenuation, of, inflammatory, 'M1', macrophages, was]), verbo([associated]), complemento([with, a, concomitant, shift, towards, alternatively, activated, 'M2', state, in, 'MSC-M1', 'co-cultures'])]). relacion([sujeto(['In', 'contrast,', alternate, macrophage, '(', 'M2)', activation, was]), verbo([enhanced]), complemento([in, 'MSC-M2', 'co-cultures'])]). relacion([sujeto(['Functional', significance, of, 'MSC-mediated', macrophage, activation, shifts, was, further, validated, on, human, endothelial, cells, prone, to, 'M1']), verbo([mediated]), complemento([injury])]). relacion([sujeto(['In', 'conclusion,', we, propose, a, novel, role, for, 'MSC', secreted, factors]), verbo([induced]), complemento([at, the, 'MSC-macrophage', interface, in, 're-educating', macrophages, by, manipulating, metabolic, programs, in, differentially, polarized, macrophages])]). relacion([sujeto(['In', 'Alzheimer\'s', 'disease,', the, microtubule, cytoskeleton, is, 'compromised,']), verbo([leading]), complemento([to, neuronal, dysfunction, and, eventually, cell, death])]). relacion([sujeto(['NAP']), verbo([prevented]), complemento([as, well, as, reversed, these, phenotypes, even, after, they, had, become, established])]). relacion([sujeto(['We']), verbo([found]), complemento([that, 'SAL', mimicked, 'NAP\'s', protective, 'effects,', by, preventing, axonal, transport, disruption, and, improving, behavioural, 'deficits,', suggesting, both, 'NAP', and, 'SAL', may, act, via, a, common, mechanism])]). relacion([sujeto(['Our', data]), verbo([suggests]), complemento([this, domain, may, be, central, to, the, microtubule, stabilising, function, of, both, peptides, and, the, mechanism, by, which, they, rescue, phenotypes, in, this, model, of, tauopathy])]). relacion([sujeto(['However,', drug]), verbo([targets]), complemento([are, often, poorly, defined, in, the, 'literature,', both, for, launched, drugs, and, for, potential, therapeutic, agents, in, discovery, and, development])]). relacion([sujeto(['Here,', we, present, an, updated, comprehensive, map, of, molecular]), verbo([targets]), complemento([of, approved, drugs])]). relacion([sujeto(['These', biomolecules, include, 667, 'human-genome-derived', proteins]), verbo([targeted]), complemento([by, drugs, for, human, disease])]). relacion([sujeto(['Analysis', of, these, drug]), verbo([targets]), complemento([indicates, the, continued, dominance, of, privileged, target, families, across, disease, 'areas,', but, also, the, growth, of, novel, 'first-in-class', 'mechanisms,', particularly, in, oncology])]). relacion([sujeto(['Through', the, collaboration, of, three, independent, 'teams,', we, highlight, some, of, the, ongoing, challenges, in, accurately, defining, the]), verbo([targets]), complemento([of, molecular, therapeutics, and, present, conventions, for, deconvoluting, the, complexities, of, molecular, pharmacology, and, drug, efficacy])]). relacion([sujeto(['The', commercial, strains, of, broiler, chickens]), verbo([have]), complemento([genetically, selected, to, reach, market, weight, at, younger, ages])]). relacion([sujeto(['In', order, to, sustain]), verbo([increased]), complemento([growth, rate, requires, an, efficient, assimilation, of, nutrients, from, the, intestinal, 'lumen,', which, is, permitted, through, nutrient, assimilation, through, the, enterocytes, that, is, facilitated, by, many, nutrient, transporter, proteins])]). relacion([sujeto(['These', 'trans-membrane', proteins]), verbo([have]), complemento([specific, 'action,', well, known, kinetics, and, assist, in, the, partitioning, of, nutrients, among, tissues])]). relacion([sujeto(['Amino', acids, are, transported, across, the, plasma, membrane, as, free, amino, acids, or, short, chain, peptides, through, several, independent, systems, encoded, by, various, nutrient, transporter, gene, 'products,', and, these, systems, may]), verbo([act]), complemento([on, multiple, substrates])]). relacion([sujeto(['Any', deficiency, in, amino, acid, and, peptide, transportation, results, in, metabolic, 'disorders,', illustrating, crucial, roles, being, played, by, the, 'body\'s', ability, to]), verbo([maintain]), complemento([amino, acid, homeostasis])]). relacion([sujeto(['The', ability, of, tissues, to, adapt, to, changes, in, input, of, amino, acids, related, to, numerous, external, factors, that, negatively, affect, amino, acids, utilization, appears, to, result, from, responses, that, alter, nutrient, transporter, protein, mRNA, expression, mandated, for, to]), verbo([maintain]), complemento([amino, acid, and, protein, homeostasis])]). relacion([sujeto(['Immune', checkpoint, blockaders, '(', 'ICBs)']), verbo([act]), complemento([by, unbalancing, the, immune, 'system,', thus, favoring, the, development, of, an, 'immune-mediated', antitumor, effect])]). relacion([sujeto(['ICBs']), verbo([targeting]), complemento([the, programmed, cell, death, 'receptor-1', '(', 'PD-1)', have, recently, been, investigated, in, a, number, of, advanced, 'tumors,', including, 'non-small', cell, lung, cancer, '(', 'NSCLC)'])]). relacion([sujeto(['Nivolumab,', a, fully, human, 'IgG4', kappa, directed, against, 'PD-1,']), verbo([has]), complemento([been, the, first, 'ICB', to, be, approved, for, 'second-line', treatment, of, advanced, 'NSCLC'])]). relacion([sujeto(['In', 'addition,', we, summarize, the, most, common, types, of, 'immune-related', adverse, events, '(', 'irAEs)']), verbo([associated]), complemento([with, 'nivolumab,', mainly, due, to, organ, inflammation, secondary, to, autoimmunity])]). relacion([sujeto(['IrAEs']), verbo([associated]), complemento([with, nivolumab, are, rarely, severe, in, 'intensity,', and, often, resolve, with, prompt, management])]). relacion([sujeto(['This', structure, is, presumably]), verbo([triggered]), complemento([by, an, inadvertent, 'plasma-wall', interaction, in, module, 4, resulting, in, a, high, impurity, influx, that, terminates, some, discharges, by, radiation, cooling])]). relacion([sujeto(['It', is]), verbo([suggested]), complemento([that, the, difference, in, the, polarization, angle, between, components, is, from, a, change, in, the, ellipticity, of, the, emitted, light, across, the, 'Stark', components, coupled, with, imperfect, polarization, preservation, from, an, 'in-vessel', mirror])]). relacion([sujeto(['According', to, stoichiometric, as, well, as, catalytic, 'experiments,', the, intramolecular, germylene, 'Lewis', pair]), verbo([acts]), complemento([as, a, catalyst, in, the, hydroboration, of, aldehydes, and, ketones])]). relacion([sujeto(['The', homologous, stannylene, 'Lewis', pair, forms, a, reactive, tin, hydride, during, the, 'catalysis,', which, can, also]), verbo([act]), complemento([as, a, catalyst, in, this, transformation])]). relacion([sujeto(['While', developmental, surveillance, programs]), verbo([promote]), complemento([early, identification, of, child, developmental, 'problems,', evidence, has, indicated, suboptimal, uptake])]). relacion([sujeto(['Developmental', surveillance, rates, may, be]), verbo([increased]), complemento([by, the, addition, of, targeted, parental, and, professional, support, within, current, universal, frameworks])]). relacion([sujeto(['Defects', in, the, orexin, system]), verbo([lead]), complemento([to, narcolepsy, with, cataplexy, in, humans, and, dogs, and, can, be, experimentally, reproduced, in, rodents])]). relacion([sujeto(['At', least, six, orexin, receptor, antagonists]), verbo([have]), complemento([reached, 'Phase', 'II', or, 'Phase', 'III', clinical, trials, in, 'insomnia,', five, of, which, are, dual, orexin, receptor, antagonists, '(', 'DORAs)', that, target, both, 'OX1', and, 'OX2', receptors, '(', 'OX2Rs)'])]). relacion([sujeto(['All', clinically, tested, 'DORAs']), verbo([induce]), complemento([and, maintain, 'sleep:', 'suvorexant,', recently, registered, in, the, 'USA', and, 'Japan', for, 'insomnia,', represents, the, first, hypnotic, principle, that, acts, in, a, completely, different, manner, from, the, current, standard, medications])]). relacion([sujeto(['It', is, 'clear,', 'however,', that, in, the, 'clinic,', all, 'DORAs']), verbo([promote]), complemento([sleep, primarily, by, increasing, rapid, eye, movement, '(', 'REM)', and, are, almost, devoid, of, effects, on, 'slow-wave', '(', 'SWS)', sleep])]). relacion([sujeto(['At', 'present,', there, is, no, consensus, on, whether, the, sole, promotion, of, 'REM', sleep]), verbo([has]), complemento([a, negative, impact, in, patients, suffering, from, insomnia])]). relacion([sujeto(['However,', sleep, onset, 'REM', '(', 'SOREM),', which]), verbo([has]), complemento([been, documented, with, 'DORAs,', is, clearly, an, undesirable, 'effect,', especially, for, narcoleptic, patients, and, also, in, fragile, populations, '(', e])]). relacion([sujeto([elderly, 'patients)', where, 'REM-associated']), verbo([loss]), complemento([of, muscle, tone, may, promote, an, elevated, risk, of, falls])]). relacion([sujeto(['Debate', thus, remains, as, to, the, ideal, orexin, agent, to, achieve, a, balanced]), verbo([increase]), complemento([in, 'REM', and, 'non-rapid', eye, movement, '(', 'NREM)', sleep])]). relacion([sujeto(['Rodent', sleep, experiments, show, that, the, 'OX2R', is, the, primary]), verbo([target]), complemento([of, orexin, receptor, antagonists, in, sleep, modulation])]). relacion([sujeto(['Furthermore,', an, 'OX2R', antagonist, 'should,', in, 'theory,']), verbo([have]), complemento([a, lower, 'narcoleptic/cataplexic', potential])]). relacion([sujeto(['In', the, 'clinic,', the, situation, remains, 'equivocal,', since, 'OX2R', antagonists, are, in, early, 'stages:', 'MK-1064']), verbo([has]), complemento([completed, 'Phase', 'I,', and, 'MIN202', is, currently, in, clinical, 'Phase', 'II/III', trials])]). relacion([sujeto(['However,', data, from, insomnia, patients]), verbo([have]), complemento([not, yet, been, released])]). relacion([sujeto(['Promotional', material]), verbo([suggests]), complemento([that, balanced, sleep, is, indeed, induced, by, 'MIN-202,', whereas, in, volunteers, 'MK-1064', has, been, reported, to, act, similarly, to, 'DORAs'])]). relacion([sujeto(['This', work, revealed, that, wild, soybeans, in, 'China', also]), verbo([act]), complemento([as, important, 'SMV', hosts, and, play, a, role, in, the, transmission, and, diversity, of, 'SMVs'])]). relacion([sujeto(['Telephone', interviews, were, 'recorded,', 'de-identified,']), verbo([transcribed]), complemento([and, thematically, analysed])]). relacion([sujeto(['Cancer', 'Information', and, 'Support', nurses, internationally]), verbo([act]), complemento([as, expert, 'navigators,', educators, and, compassionate, communicators, who, '\'', listen, between, the, 'lines\'', to, enable, callers, to, better, understand, and, contextualise, their, situation, and, discuss, it, with, their, healthcare, team, and, family, and, friends])]). relacion([sujeto(['The', expression, of, 'microRNA 21', '(', 'miR-21)']), verbo([has]), complemento([been, reported, to, be, upregulated, in, various, types, of, 'cancer,', including, malignant, gliomas])]). relacion([sujeto(['The', present, study, determined, that]), verbo([increased]), complemento([expression, of, 'miR‑21', significantly, promoted, the, migration, and, invasion, of, glioma, 'cells,', which, was, accompanied, by, an, upregulated, expression, of, the, 'Sox2', protein])]). relacion([sujeto(['Sox2', overexpression, also]), verbo([promoted]), complemento([glioma, cell, migration, and, 'invasion,', whereas, 'Sox2', siRNA, markedly, reduced, the, 'miR‑21‑enhanced', migration, and, invasion, of, glioma, 'cells,', indicating, 'Sox2', may, act, as, a, crucial, mediator, of, 'miR‑21', function])]). relacion([sujeto(['BIO,', a, 'β‑catenin', specific, 'agonist,']), verbo([enhanced]), complemento([migration, and, invasion, of, glioma, cells])]). relacion([sujeto(['XAV‑939,', an, inhibitor, of, 'β‑catenin', 'signaling,', markedly]), verbo([inhibited]), complemento([the, migration, and, invasion, of, glioma, 'cells,', suggesting, that, 'β‑catenin', may, be, associated, with, 'miR‑21‑', and, 'Sox2‑induced', invasion, of, glioma, cells])]). relacion([sujeto(['Notably,', 'BIO', restored, the, migration, and, invasion, potential, of, glioma, 'cells,', which, were]), verbo([inhibited]), complemento([by, 'Sox2', siRNA, and, 'anti‑miR‑21'])]). relacion([sujeto(['Therefore,', the, present, study, identified, the, 'miR‑21/Sox2/β‑catenin', signaling, 'pathway,', which, may]), verbo([regulate]), complemento([the, migration, and, invasion, of, human, glioma, cells])]). relacion([sujeto(['Silent', brain, lesions, due, to, thrombogenicity, of, the, procedure, represent]), verbo([recognized]), complemento([side, effects, of, atrial, fibrillation, '(', 'AF)', catheter, ablation])]). relacion([sujeto(['Embolic', risk, is, higher, if, anticoagulation, is, inadequate, and, recent, studies]), verbo([suggest]), complemento([that, uninterrupted, 'anticoagulation,', 'ACT', levels, above, 300, seconds, and, administration, of, a, 'pre-transeptal', bolus, of, heparin, might, significantly, reduce, the, incidence, of, silent, cerebral, ischemia, '(', 'SCI)', to, 2, '%'])]). relacion([sujeto(['Asymptomatic', new, lesions, during, 'AF', ablation, should]), verbo([suggest]), complemento([worse, neuropsychological, outcome, as, a, result, of, the, association, between, silent, cerebral, infarcts, and, increased, 'long-term', risk, of, dementia, in, 'non-ablated', 'AF', patients])]). relacion([sujeto(['To', 'date,', no, study]), verbo([has]), complemento([definitely, linked, 'post-operative', asymptomatic, cerebral, events, to, a, decline, in, neuropsychological, performance])]). relacion([sujeto(['Larger', volumes, of, cerebral, lesions]), verbo([have]), complemento([been, associated, with, cognitive, decline, but, are, uncommon, findings, acutely, in, 'post-ablation', 'AF', patients])]). relacion([sujeto(['Of', 'note,', the, majority, of, acute, lesions]), verbo([have]), complemento([a, small, or, medium, size, and, often, regress, at, a, 'medium-term', 'follow-up'])]). relacion([sujeto(['Successful', 'AF', ablation]), verbo([has]), complemento([the, potential, to, reduce, the, risk, of, larger, 'SCI', that, may, be, considered, as, part, of, the, natural, course, of, 'AF'])]). relacion([sujeto(['In', contrast, to, the]), verbo([increased]), complemento([research, interest, in, the, benefits, of, mindfulness, and, 'self-compassion,', relatively, few, studies, have, examined, their, unique, and, combined, effects, in, predicting, affect])]). relacion([sujeto(['Five', 'FFMQ', facets, were, 'explored:', 'observe,', 'describe,']), verbo([act]), complemento([with, 'awareness,', 'non-judgment,', and, 'non-reactivity'])]). relacion([sujeto(['When', simultaneously, examining, all, seven, facets, of, mindfulness, and, 'self-compassion,', three, of, the, five, 'FFMQ', facets, and, 'SCS', 'Neg', significantly, predicted, both, depressive, symptoms, and, negative, 'affect,', with, 'SCS', 'Neg', and]), verbo([act]), complemento([with, awareness, being, the, strongest, predictors])]). relacion([sujeto(['These', findings]), verbo([suggest]), complemento([that, a, harsh, attitude, towards, oneself, and, a, lack, of, attention, when, acting, have, the, greatest, value, in, predicting, the, presence, of, psychological, symptoms])]). relacion([sujeto(['With', respect, to, positive, 'affect,', four, of, the, five, 'FFMQ', facets, '(', except, 'non-judgment)', were, significant, 'predictors,', with, no, unique, predictive, value, of, the, two, 'SCS\'s', 'facets,']), verbo([suggesting]), complemento([that, mindfulness, is, a, more, important, predictor, of, positive, affect, than, 'self-compassion,', as, measured, by, the, 'FFMQ', and, 'SCS'])]). relacion([sujeto(['The', theory]), verbo([suggests]), complemento(['that,', following, an, information, 'scent,', the, information, seeker, must, optimize, the, tradeoff, between, exploration, by, repeated, steps, in, the, search, space, vs])]). relacion([sujeto(['Our', findings, from, an, 'eye-tracking', study, of, 'experts\'', interactions, with, novel, search, interfaces, in, the, biomedical, domain]), verbo([suggest]), complemento([that, user, traits, of, cognitive, styles, and, perceived, search, task, difficulty, are, significantly, correlated, with, eye, gaze, and, search, behavior])]). relacion([sujeto(['Since', the, pattern, of, behavior, in, information, foraging, is, quintessentially, 'sequential,', risk, and, ambiguity, minimization, cannot, happen, 'simultaneously,']), verbo([leading]), complemento([to, a, fundamental, limit, on, how, good, such, a, tradeoff, can, be])]). relacion([sujeto(['No']), verbo([increase]), complemento([in, tumour, grade, was, seen, at, time, of, recurrence])]). relacion([sujeto(['Based', on, this, 'study,', we]), verbo([have]), complemento([been, able, to, classify, the, 'post-operative', 'MRI', appearances, into, four, groups])]). relacion([sujeto(['These', groups, differ, in, 'follow-up,', and]), verbo([have]), complemento([a, different, risk, of, recurrence, of, the, lesion])]). relacion([sujeto(['While', migraine, can, be, treated, using, 'CGRP', antagonists, that]), verbo([act]), complemento(['peripherally,', the, relevant, sites, of, 'CGRP', action, remain, unknown])]). relacion([sujeto(['Following', 'IP', 'CGRP,', motility, was]), verbo([decreased]), complemento([in, the, dark, 'only,', similar, to, motility, changes, following, 'ICV', 'CGRP'])]). relacion([sujeto(['In', 'addition,', as, with, 'ICV', 'CGRP,', there, was, no, general]), verbo([increase]), complemento([in, anxiety, as, measured, in, an, open, field, assay, following, 'IP', 'CGRP'])]). relacion([sujeto(['To', begin, to, address, the, mechanism, of, peripheral, 'CGRP', 'action,', we, used, transgenic, 'CGRP-sensitized', mice, that]), verbo([have]), complemento([elevated, levels, of, the, 'CGRP', receptor, hRAMP1, subunit, in, nervous, tissue, '(', 'nestin/hRAMP1)'])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, 'CGRP', can, act, in, both, the, periphery, and, the, brain, by, distinct, mechanisms, and, that, 'CGRP', actions, may, be, transmitted, to, the, 'CNS', via, indirect, sensitization, of, peripheral, nerves])]). relacion([sujeto(['Some', preclinical, studies]), verbo([have]), complemento([pointed, to, central, sites, in, the, brain, and, brainstem])]). relacion([sujeto(['However,', a, peripheral, site, of, action, is, indicated, by, the, ability, of, intravenous, 'CGRP', to]), verbo([trigger]), complemento([migraine, in, humans, and, the, efficacy, of, 'CGRP', receptor, antagonists, that, evidently, do, no, penetrate, the, 'CNS', in, effective, amounts])]). relacion([sujeto(['Resolving', this, issue, is, particularly, important, given, recent, clinical, trials, showing, that, 'anti-CGRP', monoclonal, antibodies, can, reduce, and, even]), verbo([prevent]), complemento([migraine, attacks])]). relacion([sujeto(['In', this, 'study,', we]), verbo([report]), complemento([that, 'CGRP', can, act, in, both, the, brain, and, the, periphery, of, the, mouse, to, cause, 'migraine-like', photophobia, by, apparently, distinct, mechanisms])]). relacion([sujeto(['A', significant, fraction, of, those, proteins, are, predicted, to]), verbo([have]), complemento([catalytic, properties])]). relacion([sujeto(['Here', we, aimed, at, identifying, the, function, of, the, 'Saccharomyces', cerevisiae, 'Ydr109c', protein, and, of, its, human, homolog, 'FGGY,', both, of, which, belong, to, the, broadly]), verbo([conserved]), complemento(['FGGY', family, of, carbohydrate, kinases])]). relacion([sujeto(['Functionally', identified, members, of, this, family]), verbo([phosphorylate]), complemento([3, -, to, 7, -, carbon, sugars, or, sugar, 'derivatives,', but, the, endogenous, substrate, of, 'S'])]). relacion([sujeto([cerevisiae, 'Ydr109c', and, human, 'FGGY']), verbo([has]), complemento([remained, unknown])]). relacion([sujeto(['In', human, 'HEK293', 'cells,', ribulose, could, only, be, detected, when, ribitol, was, added, to, the, cultivation, medium, and, under, this, 'condition,', 'FGGY', silencing]), verbo([led]), complemento([to, ribulose, accumulation])]). relacion([sujeto([cerevisiae, 'Ydr109c', and, human, 'FGGY', could]), verbo([act]), complemento([as, metabolite, repair, 'enzymes,', serving, to, 're-phosphorylate', free, 'D-ribulose', generated, by, promiscuous, phosphatases, from, 'D-ribulose-5-phosphate'])]). relacion([sujeto(['In', human, 'cells,', 'FGGY', can, additionally]), verbo([participate]), complemento([in, ribitol, metabolism])]). relacion([sujeto(['Of', the, three, classes, of, enzymes]), verbo([involved]), complemento([in, 'ubiquitination,', 'ubiquitin-conjugating', enzymes, '(', 'E2)', have, been, often, incorrectly, considered, to, play, merely, an, auxiliary, role, in, the, process, and, few, 'E2', enzymes, have, been, investigated, in, plants])]). relacion([sujeto(['To']), verbo([reveal]), complemento([the, role, of, 'E2', in, plant, innate, immunity, we, identified, and, cloned, forty, tomato, genes, encoding, 'E2', proteins])]). relacion([sujeto(['Phylogenetic', analysis, classified, the, forty, tomato, 'E2', into, thirteen, 'groups,', of, which, members, of, group, 'III', were]), verbo([found]), complemento([to, interact, and, act, specifically, with, 'AvrPtoB,', a, 'Pseudomonas', syringae, pv])]). relacion([sujeto([tomato, '(', 'Pst)', effector, that, uses, its, ubiquitin, ligase, '(', 'E3)', activity, to]), verbo([suppress]), complemento([host, immunity])]). relacion([sujeto(['By', 'contrast,', 'PCD']), verbo([induced]), complemento([by, several, 'ETI', elicitors, was, not, affected, on, 'group-III-silenced', plants])]). relacion([sujeto(['Functional', characterization]), verbo([suggested]), complemento([redundancy, among, group, 'III', members, for, their, role, in, the, suppression, of, plant, immunity, by, 'AvrPtoB', and, in, 'PTI', and, identified, 'UBC11,', 28, ',', 29, ',', 39, and, 40, as, playing, a, more, significant, role, in, 'PTI', than, other, group, 'III', members])]). relacion([sujeto(['Our', work, builds, a, foundation, for, further, characterization, of, 'E2s', in, plant, immunity, and]), verbo([reveals]), complemento([that, 'AvrPtoB', has, evolved, a, strategy, for, suppressing, host, immunity, that, is, difficult, for, the, plant, to, thwart])]). relacion([sujeto(['Transforming', growth, factor, β, '(', 'TGF-β)', family, signaling, dictates, highly, complex, programs, of, gene, expression, 'responses,', which, are, extensively]), verbo([regulated]), complemento([at, multiple, levels, and, vary, depending, on, the, physiological, context])]). relacion([sujeto([',', the, 'TGF-β', receptor, complexes, and, the, 'Smad', complexes, that]), verbo([act]), complemento([as, central, mediators, of, 'TGF-β', 'signaling)', are, direct, targets, for, posttranslational, regulation])]). relacion([sujeto(['Dysfunction', of, these, complexes, often]), verbo([leads]), complemento([or, contributes, to, pathogenesis, in, cancer, and, fibrosis, and, in, 'cardiovascular,', and, autoimmune, diseases])]). relacion([sujeto(['It', is, now, evident, that, these, modifications]), verbo([act]), complemento([as, decisive, factors, in, defining, the, intensity, and, versatility, of, 'TGF-β', responsiveness])]). relacion([sujeto(['Here', we]), verbo([find]), complemento(['that,', in, colonic, crypt, 'cultures,', the, 'GLP-1', secretion, induced, by, such, 'Gq + Gs', 'GPR40', agonists, is, indeed, inhibited, by, blockers, of, both, 'Gq', and, 'Gs', and, is, eliminated, by, combining, these])]). relacion([sujeto(['GPR119', and, 'TGR5']), verbo([provide]), complemento([more, than, additive, 'GLP-1', secretion, both, ex, vivo, and, in, vivo, in, mice])]). relacion([sujeto([long, chain, fatty, acids, and, 2, -, monoacyl, glycerol, plus, bile, 'acids,']), verbo([act]), complemento([synergistically, through, their, respective, 'receptors,', 'GPR40,', 'GPR119', and, 'TGR5', to, stimulate, 'GLP-1', secretion, robustly, by, combining, 'Gq', and, 'Gs', signaling, pathways])]). relacion([sujeto(['In', this, 'regard,', some, dietary, components, from, a]), verbo([regular]), complemento([human, meal, might, have, various, 'DNA-damaging', compounds])]). relacion([sujeto(['Given', that, not, every, person, endure, 'cancer,', the, colonic, malignancy, develops, throughout, 'decades,', and, persistent, 'DNA', damage]), verbo([promotes]), complemento([cancer, when, induced, at, the, proper, 'intensity,', a, critical, discussion, of, possible, novel, mechanisms, by, which, carcinogens, promote, these, tumors, is, urgently, needed])]). relacion([sujeto(['Robust', genomic, sequencing, analyses, showed, that, low, and, late, cell, cycle]), verbo([expressed]), complemento([genes, are, prone, to, undergo, mutation])]). relacion([sujeto(['Moreover,', detection, and, repair, mechanisms]), verbo([have]), complemento([a, particular, threshold, to, be, activated, throughout, the, 'G2/M', 'phase,', and, reactivation, of, these, devices, during, the, 'M', phase, promotes, genomic, instability])]). relacion([sujeto(['Conditions', of, combined, exposure, to, 'non-genotoxic', concentrations, of, various, carcinogens, seem, to]), verbo([act]), complemento([effectively, through, these, weaknesses, in, genomic, repair, mechanisms])]). relacion([sujeto(['Therefore,', we]), verbo([suggest]), complemento([that, the, natural, tolerance, of, body, defence, mechanisms, eventually, become, overwhelmed, by, the, chronic, exposure, to, different, combinations, and, intensities, of, dietary, mutagens, leading, to, the, high, incidence, of, colon, cancer, in, modern, society])]). relacion([sujeto(['In', the, present, study, we]), verbo([have]), complemento([synthesized, a, new, class, of, 4, -, aminoquinolines, and, evaluated, against, 'Plasmodium', falciparum, in, vitro, '(', 3, 'D7-sensitive', strain, &, 'amp;', 'K1-resistant', 'strain)', and, 'Plasmodium', yoelii, in, vivo, '(', 'N-67', 'strain)'])]). relacion([sujeto(['Further,', biophysical, studies]), verbo([suggest]), complemento([that, this, series, of, compounds, act, on, heme, polymerization, target])]). relacion([sujeto(['International', recommendations, set, out, numerous, precautions, which, must, be, taken, to]), verbo([ensure]), complemento([that, donors, act, with, their, free, will])]). relacion([sujeto(['Oxidative', stress]), verbo([caused]), complemento([by, a, sharp, growth, of, free, radicals, in, the, organism, is, a, major, cause, underlying, the, occurrence, of, all, kinds, of, malignant, formations])]). relacion([sujeto(['Selenium', is, an, important, essential, trace, element]), verbo([found]), complemento([in, selenoproteins, in, the, form, of, 'selenocysteine,', an, amino, acid, differing, from, cysteine, for, the, presence, of, selenium, instead, of, sulfur, and, making, such, proteins, highly, active])]). relacion([sujeto(['To', date, the, role, of, selenium]), verbo([has]), complemento([been, extensively, investigated, through, studying, the, functions, of, selenoproteins, in, carcinogenesis])]). relacion([sujeto(['Analysis', of, the, obtained, results, clearly, demonstrates, that, selenoproteins, can]), verbo([act]), complemento([as, 'oncosuppressors,', but, can, 'also,', on, the, 'contrary,', favor, the, formation, of, malignant, tumors])]). relacion([sujeto(['Although', some, studies, in, animal, models]), verbo([reported]), complemento([no, damage, to, 'DA', nerve, endings, in, the, striatum, and, no, significant, changes, in, brain, monoamine, 'levels,', some, others, suggested, a, rapid, reduction, in, 5, -, 'HT', and, 'DA', transporter, function])]). relacion([sujeto(['Oxidative', stress, cytotoxicity, and, an]), verbo([increase]), complemento([in, frontal, cortex, lipid, peroxidation, were, also, reported])]). relacion([sujeto(['In', vitro, cytotoxic, properties, were, also, 'observed,']), verbo([suggesting]), complemento([that, mephedrone, may, act, as, a, reductant, agent, and, can, also, determine, changes, in, mitochondrial, respiration])]). relacion([sujeto(['nucifera)', was, one, of, the, versatile, trees, in, tropical, regions, which, also, can]), verbo([act]), complemento([as, a, thrust, quencher, in, all, over, the, world])]). relacion([sujeto(['Eco-friendly']), verbo([mediated]), complemento(['Pd', 'NPs', were, further, subjected, to, several, biological, applications, like, larvicidal, against, 'Aedes', aegypti, '(', 'A'])]). relacion([sujeto(['Recent']), verbo([reports]), complemento([indicate, that, 'model-based', iterative, reconstruction, methods, may, improve, image, quality, in, computed, tomography, '(', 'CT)'])]). relacion([sujeto(['Unfortunately,', this, approach]), verbo([requires]), complemento([the, selection, of, a, preferred, objective, function, and, does, not, provide, clear, information, on, features, that, are, intrinsic, to, the, model])]). relacion([sujeto(['Task-based', assessment, appears, to, be]), verbo([required]), complemento([to, appreciate, the, differences, in, 'noise;', the, estimation, task, the, authors, selected, showed, that, these, differences, balance, out, to, yield, similar, performance])]). relacion([sujeto(['Some', scenarios, highlighted, merits, for, the, 'distance-driven', method, in, terms, of, bias, but, with, an]), verbo([increase]), complemento([in, computational, cost])]). relacion([sujeto(['The', 'distance-driven', method, offers, the, possibility, to, reduce, bias, but, with, an]), verbo([increase]), complemento([in, computational, cost])]). relacion([sujeto(['Last,', strong, 'edge-preserving', penalty, can]), verbo([act]), complemento([as, a, compensator, for, insufficiencies, in, the, forward, projection, 'model,', bringing, all, models, to, similar, levels, in, the, most, challenging, imaging, scenarios])]). relacion([sujeto(['Also,', the, authors]), verbo([find]), complemento([that, their, evaluation, methodology, helps, appreciating, how, 'model,', statistical, 'weights,', and, penalty, term, interplay, together])]). relacion([sujeto(['On', 'January', 28, ',', 2015, a, depredation, event, was, recorded, 14, m, from, an, integrated, 'GoPro', 'camera,', 'hydrophone,', and, 'accelerometer,']), verbo([revealed]), complemento([that, false, killer, whales, depredate, bait, and, generate, clicks, and, whistles, under, good, visibility, conditions])]). relacion([sujeto(['The']), verbo([act]), complemento([of, plucking, bait, off, a, hook, generated, a, distinctive, 15, 'Hz', line, vibration])]). relacion([sujeto(['Predicted', detection, ranges, of, the, most, intense, whistles, are, 10, to, 25, km, at, respective]), verbo([sea]), complemento([states, of, 4, and, 1, ',', with, click, detection, ranges, being, 5, times, smaller, than, whistles])]). relacion([sujeto(['These', detection, range, analyses]), verbo([provide]), complemento([insight, into, how, passive, acoustic, monitoring, might, be, used, to, both, quantify, and, avoid, depredation, encounters])]). relacion([sujeto(['Synthetic', progestins]), verbo([act]), complemento([as, endocrine, disrupters, in, fish, but, their, risk, to, the, environment, is, not, sufficiently, known])]). relacion([sujeto(['First,', we, studied, agonistic, and, antagonistic, activities, of, 'CMA,', 'CPA,', and, 17, 'α-ethinylestradiol', '(', 'EE2),', in, recombinant, yeast]), verbo([expressing]), complemento([either, the, human, progesterone, '(', 'PGR),', androgen, '(', 'AR),', or, estrogen, receptor])]). relacion([sujeto(['The', same, compounds, were, also, investigated, in, vitro, in, a, stable, transfection, cell, system]), verbo([expressing]), complemento([rainbowfish, nuclear, steroid, receptors])]). relacion([sujeto(['CMA']), verbo([led]), complemento([to, slight, 'down-regulation', of, the, ar, 'transcript,', while, 'CPA', 'down-regulated', ar, and, pgr, transcripts])]). relacion([sujeto(['Our', study, demonstrates, that, 'CMA', and, 'CPA']), verbo([interact]), complemento([distinctly, with, human, and, rainbowfish, 'receptors,', suggesting, that, activities, of, these, and, possibly, additional, environmental, steroids, determined, with, yeast, expressing, human, receptors, cannot, simply, be, translated, to, fish])]). relacion([sujeto(['The', lack, of, agonistic, activities, of, both, progestins, to, rainbowfish, 'PGR', and, 'AR', is, the, probable, reason, for, the, low, activity]), verbo([found]), complemento([in, zebrafish, 'eleuthero-embryos'])]). relacion([sujeto(['The', oxidation, of, 's-triazines', '(', using, atrazine, '(', 'ATZ)', as, a, model, 'compound)', by, a, 'solar-enhanced', 'Fenton-like', process]), verbo([involving]), complemento([persulfate, and, ferrous, ion, was, studied])]). relacion([sujeto(['The', 'solar-enhanced', oxidative, system]), verbo([involving]), complemento([ferrous, ion, and, persulfate, '(', 'Solar/S2O8(2-)/Fe(2+))', showed, the, highest, 'ATZ', degradation, efficiency, when, compared, with, other, treatments, '(', unactivated, 'S2O8(2-),', 'Solar', -, sunlight, 'only,', 'S2O8(2-)/Fe(2+),', 'Solar/S2O8(2-))'])]). relacion([sujeto(['The', in, situ, generated, '(', '•', ')', 'ОН', and, 'SO4(-•)', radicals, were, shown, to, be]), verbo([involved]), complemento([in, 'ATZ', oxidation, using, the, radical, scavengers, methanol, and, 'tert-butyl', alcohol])]). relacion([sujeto(['Furthermore,', iron, compounds, were, shown, to]), verbo([act]), complemento([not, only, as, catalysts, but, also, as, 'photo-sensitizers,', as, the, introduction, of, ferrous, ion, into, the, reaction, mixture, led, to, an, increased, absorbance, of, the, solution, and, expansion, of, the, absorption, spectrum, into, the, longer, wavelength, spectral, region])]). relacion([sujeto([oryzae, '(', 'Xoo)']), verbo([causes]), complemento([the, serious, bacterial, blight, disease, of, rice])]). relacion([sujeto([',', which]), verbo([act]), complemento([on, various, components, of, the, rice, cell, wall])]). relacion([sujeto(['The', major, cellulases, and, xylanases, secreted, by, 'Xoo']), verbo([have]), complemento([been, identified, and, their, role, in, virulence, has, been, determined])]). relacion([sujeto(['In', this, 'study,', we]), verbo([have]), complemento([identified, some, of, the, pectin, degrading, enzymes, of, 'Xoo', and, assessed, their, role, in, virulence])]). relacion([sujeto(['There', was, no, difference, in, the, expression, of, 'pglA,', pmt, and, pel, genes, by, laboratory, wild, type, 'Xoo', strain, '(', 'BXO43)', grown, in, either, nutrient, rich, 'PS', medium, or, in, plant, mimic, 'XOM2', medium, whereas, the, expression, of, pelL, gene, was]), verbo([induced]), complemento([in, 'XOM2', medium, as, indicated, by, 'qRT-PCR', experiments])]). relacion([sujeto(['Mutations', in, the, 'pglA,', 'pmt,', pel, and, pelL, genes]), verbo([have]), complemento([minimal, effects, on, virulence])]). relacion([sujeto(['This']), verbo([suggests]), complemento(['that,', as, compared, to, cellulases, and, 'xylanases,', the, 'HG', degrading, enzymes, may, not, have, a, major, role, in, the, pathogenicity, of, 'Xoo'])]). relacion([sujeto(['After', 3, 'months,', compared, to, patients, who, received, education, 'alone,', those, in, the, 'group-based', acceptance, and, commitment, therapy, condition, were, more, likely, to, use, effective, coping, 'strategies,']), verbo([reported]), complemento([better, diabetes, 'self-care,', and, optimum, glycated, hemoglobin, '(', 'HbA1C)', levels, in, the, target, range])]). relacion([sujeto(['Consideration', of, the, role, of, coping, style, for, a, more, accurate, evaluation, of, the, effects, of, acceptance, and, commitment, therapy, may, be, a, useful, addition, to, services]), verbo([provided]), complemento([for, patients, with, type, 2, diabetes])]). relacion([sujeto(['To', be, eligible, for, 'inclusion,', patients, had, to]), verbo([have]), complemento([a, high, clinical, suspicion, of, an, 'infection,', together, with, a, systemic, inflammatory, response, '(', 'sepsis)', and, evidence, of, acute, organ, dysfunction, 'and/or', shock, '(', severe, 'sepsis)'])]). relacion([sujeto(['Multivariable', logistic, regression, analysis, identified, higher, 'National', 'Early', 'Warning', 'Score,', 'diabetes,', 'COPD,', heart, 'failure,', malignancy, and, current, or, previous, smoking, habits, as, independent, variables]), verbo([suggesting]), complemento([the, diagnosis, of, sepsis])]). relacion([sujeto(['We', observed, that, sepsis, is, more, prevalent, in, the, general, ward, and, 'ED', than, previously]), verbo([suggested]), complemento([before, and, that, screening, and, effective, treatment, for, sepsis, and, severe, sepsis, is, far, from, being, operationalized, in, this, 'environment,', leading, to, high, 90, days, mortality])]). relacion([sujeto(['Exercise', is, one, lifestyle, factor, that]), verbo([has]), complemento([been, identified, as, a, potential, means, of, reducing, or, delaying, progression, of, the, symptoms, of, 'dementia,', maximizing, function, and, independence])]). relacion([sujeto(['To']), verbo([increase]), complemento([trustworthiness, the, study, used, triangulation, within, investigators, and, member, checking])]). relacion([sujeto(['The', core, category, &, 'quot;Discover', and]), verbo([act]), complemento([in, the, 'moment-learn', over, 'time"', reflects, how, the, 'PTs', continuously, developed, their, own, learning, in, an, iterative, process])]). relacion([sujeto(['Accumulating', studies]), verbo([have]), complemento([demonstrated, that, long, noncoding, 'RNAs', '(', 'lncRNAs)', act, a, crucial, role, in, the, development, of, tumors])]). relacion([sujeto(['Ectopic', expression, of, 'RMRP']), verbo([promoted]), complemento([lung, adenocarcinoma, cell, 'proliferation,', colony, formation, and, invasion])]). relacion([sujeto(['In', 'addition,', overexpression, of, 'RMRP']), verbo([inhibited]), complemento([the, 'miR-206', expression, in, the, 'H1299', cell, and, increased, the, 'KRAS,', 'FMNL2', and, 'SOX9', 'expression,', which, were, the, target, genes, of, 'miR-206'])]). relacion([sujeto(['Our', data, proved, that, 'RMRP']), verbo([acted]), complemento([as, an, oncogene, 'LncRNA', to, promote, the, expression, of, 'KRAS,', 'FMNL2', and, 'SOX9', by, inhibiting, 'miR-206', expression, in, lung, cancer])]). relacion([sujeto(['These', data]), verbo([suggested]), complemento([that, 'RMRP', might, serve, as, a, therapeutic, target, in, lung, adenocarcinoma])]). relacion([sujeto(['This']), verbo([increase]), complemento([in, urbanization, poses, new, challenges, for, the, spread, and, control, of, communicable, diseases, such, as, malaria])]). relacion([sujeto(['Interestingly', 'India,', as, opposed, to, 'Africa,', harbors, a, mosquito, 'vector,', 'Anopheles', 'stephensi,', which, thrives, in, the, 'man-made', environments, of, cities, and]), verbo([acts]), complemento([as, the, vector, for, both, 'Plasmodium', vivax, and, 'Plasmodium', 'falciparum,', making, the, malaria, problem, a, truly, urban, phenomenon])]). relacion([sujeto(['Malaria', risk, is, then, shown, to, be]), verbo([associated]), complemento([with, socioeconomic, indicators, and, environmental, 'parameters,', temperature, and, humidity])]). relacion([sujeto(['Climate', forcing, and, 'socio-economic', heterogeneity]), verbo([act]), complemento([synergistically, at, local, scales, on, the, population, dynamics, of, urban, malaria, in, this, city])]). relacion([sujeto(['The', stationarity, of, malaria, risk, patterns]), verbo([provides]), complemento([a, basis, for, more, targeted, 'intervention,', such, as, vector, 'control,', based, on, transmission, '\'', 'hotspots\''])]). relacion([sujeto(['It']), verbo([has]), complemento([been, claimed, that, many, of, the, 'law\'s', reforms, are, now, so, integrated, in, the, health, system, that, full, repeal, would, be, 'impractical,', while, others, including, 'President', 'Elect', 'Trump', have, rejected, that, idea, and, called, for, full, repeal, and, replacement, claiming, 'ACA', law, cannot, be, fixed])]). relacion([sujeto(['A', tsunami, of]), verbo([increasing]), complemento([regulatory, burden, over, the, past, 8, 'years,', the, current, health, care, milieu, has, moved, independent, practitioners, towards, hospital, employment, in, great, numbers])]). relacion([sujeto(['In', 'addition,', public, opinion]), verbo([has]), complemento([been, slowly, climbing, against, 'ObamaCare', with, 54, '%', of, 'Americans', now, opposing, the, law])]). relacion([sujeto(['President', 'Obama']), verbo([has]), complemento([indicated, that, the, law, has, accomplished, many, of, its, 'goals,', including, increasing, 'accessibility,', 'affordability,', and, quality, of, health, care])]). relacion([sujeto(['However,', others]), verbo([have]), complemento([contradicted, these, assertions, and, described, the, 'ACA', as, &, 'quot;insurance', for, many, with, coverage, for, few])]). relacion([sujeto(['The', 'President-elect']), verbo([has]), complemento([described, the, problems, he, perceives, with, the, 'ACA;', rapidly, rising, premiums, and, 'deductibles,', narrow, 'networks,', and, limits, of, coverage, imposed, by, health, insurance, companies])]). relacion([sujeto(['The', 'President-elect']), verbo([has]), complemento([indicated, that, his, goal, will, be, to, create, a, 'patient-centered', health, care, system, that, promotes, 'choice,', 'quality,', and, affordability, with, health, insurance, and, health, 'care,', and, take, any, needed, action, to, alleviate, the, burdens, imposed, on, 'American', families, and, businesses, by, law])]). relacion([sujeto(['Policymakers', are, poised, to]), verbo([act]), complemento([and, 1, proposal, entails, reorganizing, the, current, 'OPTN', of, 11, regions, into, 8, districts])]). relacion([sujeto(['However,', redistricting]), verbo([has]), complemento([the, shortcomings, that, 'OPOs', are, disconnected, from, their, immediate, neighbors, by, district, borders, and, that, it, is, not, easily, responsive, to, uncertainty, resulting, from, variability, in, donor, and, listing, rates])]). relacion([sujeto(['We', introduce, the, notion, of, an, 'OPO\'s', neighborhood, -, a, collection, of, 'DSAs', surrounding, the, 'OPO', that]), verbo([acts]), complemento([as, the, 'OPO\'s', region, in, the, current, 'local-regional-national', framework])]). relacion([sujeto(['Orexin-1', and, 'orexin-2', receptors, '(', 'Ox1r', and, 'Ox2r)', are]), verbo([found]), complemento([at, high, density, in, the, ventrolateral, periaqueductal, gray, matter, '(', 'vlPAG)'])]). relacion([sujeto(['Our', previous, study, showed, that, chemical, stimulation, of, the, lateral, hypothalamus, with, carbachol]), verbo([induces]), complemento([antinociception, in, the, 'tail-flick', 'test,', a, model, of, acute, 'pain,', and, 'Ox1r-mediated', antinociception, in, the, vlPAG, is, modulated, by, the, activity, of, vlPAG, 'CB1', receptors])]). relacion([sujeto(['The', findings, showed, that, the, antinociceptive, effect, of, orexin, is, partially]), verbo([mediated]), complemento([by, activation, of, vlPAG, 'Ox2', receptors])]). relacion([sujeto(['It', seems, that, 'Ox2', and, 'CB1', receptors]), verbo([act]), complemento([through, different, pathways, and, 'Ox2r-mediated', antinociception, is, not, dependent, on, 'CB1', receptor, activity])]). relacion([sujeto(['Although', 'uricase-knockout', '(', 'Uox', 'KO)', mice, are]), verbo([reported]), complemento([to, develop, uric, acid, '(', 'UA)', 'nephropathy,', those, that, mature, without, severe, nephropathy, could, be, useful, for, research, into, purine, metabolism, in, humans])]). relacion([sujeto(['UA', is, thought, to]), verbo([act]), complemento([as, an, 'anti-oxidizing', agent, in, 'humans;', 'thus,', these, results, show, that, 'Uox', 'KO', mice, are, potential, animal, models, for, research, into, human, purine, metabolism])]). relacion([sujeto(['Scaffolds', produced, by, electrospinning]), verbo([act]), complemento([as, supports, for, cell, proliferation, and, 'differentiation,', improved, through, the, release, of, neurotrophic, factors])]). relacion([sujeto(['This', final, rule, continues, our, efforts, to, assist, states, in, implementing, 'Medicaid', and, 'CHIP', 'eligibility,', 'appeals,', and, enrollment, changes]), verbo([required]), complemento([by, the, 'Affordable', 'Care', 'Act'])]). relacion([sujeto(['This', action, is, based, on, a]), verbo([finding]), complemento([by, the, 'Administrator', that, the, placement, of, furanyl, fentanyl, into, schedule, 'I', of, the, 'Controlled', 'Substances', 'Act', is, necessary, to, avoid, an, imminent, hazard, to, the, public, safety])]). relacion([sujeto(['This', final, rule, supplements, the, time, and, extent, application, '(', 'TEA)', process, for, 'OTC', drugs, by, establishing, timelines, and, performance, metrics, for, 'FDA\'s', review, of, 'non-sunscreen', 'TEAs,', as]), verbo([required]), complemento([by, the, 'Sunscreen', 'Innovation', 'Act', '(', 'SIA)'])]). relacion([sujeto(['African', 'Americans', with, head, and, neck, squamous, cell, carcinoma, '(', 'HNSCC)']), verbo([have]), complemento([a, lower, survival, rate, than, whites])]). relacion([sujeto(['Genotypes', containing, the, 'African', allele, were]), verbo([associated]), complemento([with, poor, 'OS/DFS', in, comparison, with, homozygous, genotypes, harboring, the, white, allele])]). relacion([sujeto(['Analyses', show, that, 'ancestry-related', alleles, could]), verbo([act]), complemento([as, eQTLs, in, 'HNSCC', and, support, the, association, of, 'ancestry-related', genetic, factors, with, survival, disparities, in, patients, diagnosed, with, oral, cavity, and, laryngeal, cancer])]). relacion([sujeto(['We', describe, a, detailed, procedure, for, the, use, of, 'LOVTRAP,', an, approach, to, reversibly, sequester, and]), verbo([release]), complemento([proteins, from, cellular, membranes, using, light])]). relacion([sujeto(['In', the, application, described, 'here,', proteins, that]), verbo([act]), complemento([at, the, plasma, membrane, are, held, at, mitochondria, in, the, 'dark,', and, reversibly, released, by, irradiation])]). relacion([sujeto(['The', technique, relies, on]), verbo([binding]), complemento([of, an, engineered, 'Zdk', domain, to, a, 'LOV2', 'domain,', with, affinity, &, 'lt;30', nM, in, the, dark, and, &, 'gt;500', nM, upon, irradiation, between, 400, and, 500, nm])]). relacion([sujeto(['LOVTRAP', can, be, applied, to, diverse, 'proteins,', as, it]), verbo([requires]), complemento([attaching, only, one, member, of, the, 'Zdk/LOV2', pair, to, the, target, 'protein,', and, the, other, to, the, membrane, where, the, target, protein, is, to, be, sequestered])]). relacion([sujeto(['Light-induced', protein]), verbo([release]), complemento([occurs, in, less, than, a, 'second,', and, the, 'half-life', of, return, can, be, adjusted, using, 'LOV', point, mutations, '(', '∼2', to, 500, 'sec)'])]). relacion([sujeto(['The', use, of, femtosecond, lasers, to, introduce, controlled, stress, states]), verbo([has]), complemento([recently, been, demonstrated, in, silica, glass])]). relacion([sujeto(['Using', this, 'approach,', we, achieve, sufficient, retardance, to]), verbo([act]), complemento([as, a, 'quarter-wave', plate])]). relacion([sujeto(['The', stress, distribution, within, the, clear, aperture, is, analyzed, and, 'modeled,']), verbo([providing]), complemento([a, generic, template, that, can, be, used, as, a, set, of, design, rules, for, 'laser-machined', polarization, devices])]). relacion([sujeto(['Thus,', purified, 'SWCNTs,', even, bearing, oxygen, functional, 'groups,']), verbo([act]), complemento([as, inert, particles, in, the, cell, culture, medium])]). relacion([sujeto(['FTIR', spectra, confirmed, presence, of, proteins]), verbo([bound]), complemento([to, 'AgNPs', act, as, reducing, agent])]). relacion([sujeto(['Zone', of, inhibition]), verbo([increased]), complemento([with, increasing, concentration, of, 'AgNPs', with, maximum, of, 19, mm, against, 'E'])]). relacion([sujeto(['The', results, of, the, present, study]), verbo([suggest]), complemento([that, 'AgNPs', can, be, synthesised, rapidly, under, optimised, conditions, and, show, strong, antimicrobial, property, against, 'MDR', pathogens, without, having, toxicity, effect, on, human, epithelial, cells])]). relacion([sujeto(['Although', these, dietary, behaviours, may]), verbo([increase]), complemento([future, risk, of, chronic, 'disease,', limited, research, has, investigated, correlates, of, meal, skipping, in, young, adults])]). relacion([sujeto(['Correlates', were, defined, as, any, factor, that, was, either]), verbo([associated]), complemento([with, meal, skipping, or, was, 'self-reported', by, the, participant, to, have, an, influence, on, meal, skipping])]). relacion([sujeto(['Multiple', methodological, and]), verbo([reporting]), complemento([weaknesses, were, apparent, in, the, reviewed, studies, with, 28, of, the, 35, studies, scoring, a, negative, rating, in, the, risk, of, bias, assessment])]). relacion([sujeto(['Meal', skipping, '(', any, 'meal),', defined, as, the, skipping, of, any, meal, throughout, the, 'day,', was]), verbo([reported]), complemento([in, 12, studies, with, prevalence, ranging, between, 5, and, 83, '%'])]). relacion([sujeto(['Lack', of, time, was, consistently]), verbo([reported]), complemento([as, an, important, correlate, of, meal, 'skipping,', compared, with, correlates, such, as, cost, and, weight, 'control,', while, sex, was, the, most, commonly, reported, associated, correlate])]). relacion([sujeto(['Future', research, would, benefit, from, stronger, design, and]), verbo([reporting]), complemento(['strategies,', using, a, standardised, approach, for, measuring, and, defining, meal, skipping])]). relacion([sujeto(['This', action, is, based, on, a]), verbo([finding]), complemento([by, the, 'Administrator', that, the, placement, of, 'U-47700', into, schedule, 'I', of, the, 'Controlled', 'Substances', 'Act', is, necessary, to, avoid, an, imminent, hazard, to, the, public, safety])]). relacion([sujeto(['Delayed', maturation, 'can,', 'however,', still]), verbo([lead]), complemento([to, other, detrimental, morphological, and, physiological, changes, that, become, apparent, later, in, adulthood, '(', e])]). relacion([sujeto(['We']), verbo([found]), complemento([that, a, 'male\'s', diet, early, in, life, significantly, influenced, his, sperm, reserves, and, sperm, replenishment, rate])]). relacion([sujeto(['Although', delaying, maturation, to, reach, the, same, body, size, as, well, fed, juveniles, can, ameliorate, some, costs, of, a, poor, start, in, 'life,', our, findings]), verbo([suggest]), complemento([that, costs, might, still, arise, because, of, sexual, selection, against, these, males])]). relacion([sujeto(['It', should, be, 'noted,', 'however,', that, the, observed, effects, are, modest, '(', 'Hedges\'', g, =, 0.2, -, 0.36, ')', ',', and, the, assumption, that, lower, sperm, production]), verbo([translates]), complemento([into, a, decline, in, fitness, under, sperm, competition, remains, unconfirmed])]). relacion([sujeto(['Alternative', 'Payment', 'Models', are, payment, 'approaches,', developed, in, partnership, with, the, clinician, 'community,', that]), verbo([provide]), complemento([added, incentives, to, deliver, 'high-quality', and, 'cost-efficient', care])]). relacion([sujeto(['In', this, final, rule, with, comment, period, we]), verbo([have]), complemento([rebranded, key, terminology, based, on, feedback, from, 'stakeholders,', with, the, goal, of, selecting, terms, that, will, be, more, easily, identified, and, understood, by, our, stakeholders])]). relacion([sujeto(['This', rule, will, better]), verbo([prevent]), complemento([and, protect, survivors, of, family, 'violence,', domestic, 'violence,', and, dating, 'violence,', by, clarifying, that, all, survivors, must, have, access, to, services, and, programs, funded, under, the, 'Family', 'Violence', 'Prevention', and, 'Services', 'Act'])]). relacion([sujeto(['More', 'specifically,', the, rule]), verbo([enhances]), complemento([accessibility, and, 'non-discrimination', 'provisions,', clarifies, confidentiality, 'rules,', promotes, coordination, among, 'community-based', 'organizations,', 'State', 'Domestic', 'Violence', 'Coalitions,', 'States,', and, 'Tribes,', as, well, as, incorporates, new, discretionary, grant, programs])]). relacion([sujeto(['The', rule, also]), verbo([increases]), complemento([clarity, and, reduces, potential, confusion, over, statutory, and, regulatory, standards])]). relacion([sujeto(['The', rule, codifies, standards, already, used, by, the, program, in, the, 'Funding', 'Opportunity', 'Announcements', and, 'awards,', in, technical, 'assistance,', in]), verbo([reporting]), complemento(['requirements,', and, in, 'sub-regulatory', guidance])]). relacion([sujeto([&, 'quot;Buck"', 'McKeon', 'National', 'Defense', 'Authorization', 'Act', for, 'Fiscal', 'Year', 2015, which, states, that, beginning, 'October', 1, ',', 2015, ',', the, pharmacy, benefits, program, shall]), verbo([require]), complemento([eligible, covered, beneficiaries, generally, to, refill, 'non-generic', prescription, maintenance, medications, through, military, treatment, facility, pharmacies, or, the, national, 'mail-order', pharmacy, program])]). relacion([sujeto(['The', 'TRICARE', 'For', 'Life', 'Pilot', 'Program', described, in, section, 716, '(', 'f)', of, the, 'National', 'Defense', 'Authorization', 'Act', for, 'Fiscal', 'Year', 2013, ',', was, a, pilot, program, which, began, in, 'March', 2014]), verbo([requiring]), complemento(['TRICARE', 'For', 'Life', beneficiaries, to, refill, 'non-generic', prescription, maintenance, medications, through, military, treatment, facility, pharmacies, or, the, national, 'mail-order', pharmacy, program])]). relacion([sujeto(['In', these, 'dyads,', carbazole, '(', 'Cz)', and, oxadiazole, '(', 'Oz)', moieties]), verbo([act]), complemento([as, an, electron, donor, and, 'acceptor,', respectively])]). relacion([sujeto(['The', emission, maxima, of, dyads, 1, and, 3, 'red-shifted', with, the]), verbo([increase]), complemento([in, 'polarity,', which, could, be, attributed, to, the, 'ICT', process])]). relacion([sujeto(['Moreover,', the, emission, at, 470, nm]), verbo([increased]), complemento([simultaneously, with, the, diminishing, of, the, fluorescence, at, 380, nm])]). relacion([sujeto(['Based', on, the, 'fs-TA', 'studies,', it, was]), verbo([found]), complemento([that, the, dynamics, and, mechanisms, for, the, electron, '(', or, 'charge)', transfer, were, strongly, affected, by, the, variation, of, the, 'π-conjugation', of, the, linker])]). relacion([sujeto(['In', 'eukaryotes,', up, to, 'one-third', of, cellular, proteins, are]), verbo([targeted]), complemento([to, the, endoplasmic, 'reticulum,', where, they, undergo, 'folding,', 'processing,', sorting, and, trafficking, to, subsequent, endomembrane, compartments])]). relacion([sujeto(['Targeting', to, the, endoplasmic, reticulum]), verbo([has]), complemento([been, shown, to, occur, 'co-translationally', by, the, signal, recognition, particle, '(', 'SRP)', pathway, or, 'post-translationally', by, the, mammalian, transmembrane, recognition, complex, of, 40, kDa, '(', 'TRC40)', and, homologous, yeast, guided, entry, of, 'tail-anchored', proteins, '(', 'GET)', pathways])]). relacion([sujeto(['We', set, out, to, uncover, additional]), verbo([targeting]), complemento([proteins, using, unbiased, 'high-content', screening, approaches])]). relacion([sujeto(['To', this, 'end,', we, performed, a, systematic, visual, screen, using, the, yeast, 'Saccharomyces', 'cerevisiae,', and, uncovered, three, uncharacterized, proteins, whose]), verbo([loss]), complemento([affected, targeting])]). relacion([sujeto(['We']), verbo([suggest]), complemento([that, these, proteins, work, together, and, demonstrate, that, they, function, in, parallel, with, 'SRP', and, 'GET', to, target, a, broad, range, of, substrates, to, the, endoplasmic, reticulum])]). relacion([sujeto(['The', three, 'proteins,', which, we, name, 'Snd1,', 'Snd2', and, 'Snd3', '(', for, 'SRP-independent', 'targeting),', can, synthetically, compensate, for, the]), verbo([loss]), complemento([of, both, the, 'SRP', and, 'GET', 'pathways,', and, act, as, a, backup, targeting, system])]). relacion([sujeto(['This', explains, why, it]), verbo([has]), complemento([previously, been, difficult, to, demonstrate, complete, loss, of, targeting, for, some, substrates])]). relacion([sujeto(['Our', discovery, thus, puts, in, place, an, essential, piece, of, the, endoplasmic, reticulum]), verbo([targeting]), complemento(['puzzle,', highlighting, how, the, targeting, apparatus, of, the, eukaryotic, cell, is, 'robust,', interlinked, and, flexible])]). relacion([sujeto(['Classical', methods, for]), verbo([enhancing]), complemento([the, electromagnetic, field, from, substrates, for, spectroscopic, 'applications,', such, as, 'surface-enhanced', 'Raman', spectroscopy, '(', 'SERS),', have, involved, the, generation, of, hotspots, through, directed, 'self-assembly', of, nanoparticles, or, by, patterning, nanoscale, features, using, expensive, nanolithography, techniques])]). relacion([sujeto(['A', novel, 'large-area,', 'cost-effective', soft, lithographic, technique]), verbo([involving]), complemento([glancing, angle, deposition, '(', 'GLAD)', of, silver, on, polymer, gratings, is, reported, here])]). relacion([sujeto(['The', uniform, ordered, and, patterned, nanostructures]), verbo([provide]), complemento([extraordinary, field, enhancements, that, serve, as, excitatory, hotspots, and, are, herein, interrogated, by, 'SERS'])]). relacion([sujeto(['The', enhancement, was, shown, to]), verbo([have]), complemento([a, critical, dependence, on, the, underlying, nanostructure, via, the, surface, energy, landscape, and, 'GLAD', angles, for, a, fixed, deposition, 'thickness,', as, evidenced, by, atomic, force, microscopy, and, scanning, electron, microscopy, surface, analysis, of, the, substrate])]). relacion([sujeto(['The', nanostructured, surface]), verbo([leads]), complemento([to, an, extremely, concentrated, electromagnetic, field, at, sharp, nanoscale, 'peaks,', here, referred, to, as, '\'', 'nano-protrusions\',', due, to, the, coupling, of, surface, plasmon, resonance, '(', 'SPR)', with, localized, 'SPR'])]). relacion([sujeto(['These', 'nano-protrusions']), verbo([act]), complemento([as, hotspots, which, provide, 'Raman', enhancement, factors, as, high, as, 10, '(', 8, ')', over, a, comparable, 'SAM', on, silver])]). relacion([sujeto(['Alcohol', dependence, represents, a]), verbo([leading]), complemento([cause, of, mortality, and, morbidity])]). relacion([sujeto(['An', overlap, between, factors, that, may, predispose, people, to, become, obese, and, those, that, may]), verbo([increase]), complemento([the, risk, of, alcohol, dependence, may, exist])]). relacion([sujeto(['In', a, 'case-control', study, with, 829, 'participants,', factors]), verbo([involved]), complemento([with, metabolism, and, obesity, were, 'assessed,', including, biochemical, lipid, and, liver, 'markers,', and, the, fat, mass, and, 'obesity-associated', '(', 'FTO)', single, nucleotide, polymorphism, '(', 'SNP)', rs8050136])]). relacion([sujeto(['Increased', 'triglycerides,', having, one, or, two, minor, 'A', alleles, for, rs8050136, and, being, a, smoker, were]), verbo([associated]), complemento([with, increased, risk, of, alcohol, 'dependence,', while, increased, 'low-density', lipoprotein, cholesterol, was, associated, with, decreased, risk])]). relacion([sujeto(['In', 'addition,', having, abnormal, 'gamma-glutamyl', transferase, and, being, female, were, factors]), verbo([associated]), complemento([with, an, increased, severity, of, alcohol, dependence])]). relacion([sujeto(['Our', preliminary, findings]), verbo([suggest]), complemento([a, link, between, alcohol, dependence, and, 'obesity-related', biochemical, and, genetic, factors])]). relacion([sujeto(['Future', studies, are, needed, to, better, understand, if, these, factors, may, play, a, predictive, role, 'and/or', may]), verbo([act]), complemento([as, biomarkers, for, treatment, response])]). relacion([sujeto(['Dietary', polyphenols, such, as, proanthocyanidins, '(', 'PAC)', may, reduce, 'inflammation,', and, we, therefore, hypothesized, that, 'PAC', may]), verbo([suppress]), complemento([lipopolysaccharide, '(', 'LPS)', -, induced, responses, in, human, 'DCs', and, subsequent, 'T', helper, type, 1, '(', 'Th1)', -, type, responses, in, naive, 'T', cells])]). relacion([sujeto(['Moreover,', we, proposed, 'that,', because, 'DCs', are, likely, to, be, exposed, to, multiple, 'stimuli,', the, activity, of, 'PAC', may, synergise, with, other, bioactive, molecules, that]), verbo([have]), complemento(['anti-inflammatory', 'activity,', e])]). relacion([sujeto(['We', show, that, 'PAC', are, endocytosed, by, 'monocyte-derived', 'DCs', and, selectively]), verbo([induce]), complemento(['CD86', expression])]). relacion([sujeto(['Subsequently,', 'PAC']), verbo([suppress]), complemento([the, 'LPS-induced', secretion, of, 'interleukin-6', '(', 'IL-6)', and, 'IL-12p70,', while, enhancing, secretion, of, 'IL-10'])]). relacion([sujeto(['Co-pulsing', 'DCs', with, 'TsSP', and, 'PAC', synergistically, reduced, secretion, of, tumour, necrosis, 'factor-α,', 'IL-6', and, 'IL-12p70', while]), verbo([increasing]), complemento(['IL-10', secretion])]). relacion([sujeto(['Moreover,', both, 'TsSP', and, 'PAC', alone]), verbo([induced]), complemento(['Th2-associated', 'OX40L', expression, in, 'DCs,', and, together, synergized, to, 'up-regulate', 'OX40L'])]). relacion([sujeto(['These', data]), verbo([suggest]), complemento([that, 'PAC', induce, an, 'anti-inflammatory', phenotype, in, human, 'DCs', that, selectively, 'down-regulates', 'Th1', response, in, naive, 'T', 'cells,', and, that, they, also, act, cooperatively, with, 'TsSP'])]). relacion([sujeto(['Our', results, indicate, a, novel, interaction, between, dietary, compounds, and, parasite, products, to, influence, immune, 'function,', and, may]), verbo([suggest]), complemento([that, combinations, of, 'PAC', and, 'TsSP', can, have, therapeutic, potential, for, inflammatory, disorders])]). relacion([sujeto(['A', number, of, factors]), verbo([act]), complemento([synergistically, to, reduce, the, live, coral, cover, and, threaten, the, existence, of, reefs])]). relacion([sujeto(['In', 'GoM,', the]), verbo([loss]), complemento([of, live, coral, cover, was, estimated, to, be, 16.5, '%', due, to, 'C'])]). relacion([sujeto(['In', 'combination,', results, of, this, study]), verbo([suggested]), complemento([that, the, recovery, of, a, coral, reef, after, a, macroalgal, bloom, largely, depends, on, coral, species, composition, and, the, frequency, of, stress, events])]). relacion([sujeto(['A', further, study, linking, macroalgal, bloom, to, its, specific]), verbo([cause]), complemento([is, essential, for, the, successful, intervention, and, management])]). relacion([sujeto(['After', adjusting, for, 'demographics,', race, was, significantly]), verbo([associated]), complemento([with, patient, 'activation,', working, 'alliance,', and, medication, adherence, scores])]). relacion([sujeto(['Patient', activation, was, also]), verbo([associated]), complemento([with, working, alliance])]). relacion([sujeto(['These', results]), verbo([provide]), complemento([support, for, the, consideration, of, race, and, ethnicity, in, facilitating, patient, engagement, and, patient, activation, in, mental, healthcare])]). relacion([sujeto(['Minority', patients, may, benefit, from]), verbo([targeted]), complemento([efforts, to, improve, their, active, engagement, in, mental, healthcare])]). relacion([sujeto(['Cilia']), verbo([act]), complemento([primarily, in, the, generation, of, directional, fluid, flow, and, sensory, 'reception,', both, of, which, are, utilized, for, a, broad, spectrum, of, cellular, processes])]). relacion([sujeto(['Sfr1', is, part, of, a, large, family, of, 13, proteins, in, 'Tetrahymena', that, contain, 'Sfi1', repeats, '(', 'SFRs),', a, motif, originally, identified, in, 'Saccharomyces', cerevisiae, 'Sfi1', that]), verbo([binds]), complemento([centrin])]). relacion([sujeto(['Complete', genomic, knockout, of, 'SFR1', '(', 'sfr1Δ)']), verbo([causes]), complemento([a, significant, increase, in, both, cortical, row, basal, body, density, and, the, number, of, cortical, 'rows,', contributing, to, an, overall, overproduction, of, basal, bodies])]). relacion([sujeto(['Reintroduction', of, 'Sfr1', into, sfr1Δ, mutant, cells]), verbo([leads]), complemento([to, a, marked, reduction, of, cortical, row, basal, body, density, and, the, total, number, of, cortical, row, basal, bodies])]). relacion([sujeto(['Therefore,', 'Sfr1', directly]), verbo([modulates]), complemento([cortical, row, basal, body, production])]). relacion([sujeto(['This', study]), verbo([reveals]), complemento([an, inhibitory, role, for, 'Sfr1,', and, potentially, 'centrins,', in, 'Tetrahymena', basal, body, production])]). relacion([sujeto(['IMPORTANCE', 'Basal', bodies, and, centrioles, are, structurally, similar, 'and,', when, rendered, dysfunctional, as, a, result, of, improper, assembly, or, 'maintenance,', are]), verbo([associated]), complemento([with, human, diseases])]). relacion([sujeto(['Centrins', are]), verbo([conserved]), complemento([and, abundant, components, of, both, structures, whose, basal, body, and, centriolar, functions, remain, incompletely, understood])]). relacion([sujeto(['In', this, 'study,', we]), verbo([found]), complemento([that, 'Sfr1', localizes, to, all, 'Tetrahymena', basal, bodies, and, complete, genetic, deletion, of, 'SFR1', leads, to, overproduction, of, basal, bodies])]). relacion([sujeto(['The', uncovered, inhibitory, role, of, 'Sfr1', in, basal, body, production]), verbo([suggests]), complemento([that, 'centrin-binding', 'proteins,', as, well, as, 'centrins,', may, influence, basal, body, number, both, positively, and, negatively])]). relacion([sujeto(['Valiant', efforts, to, drug, mutant, 'K-Ras', and, related, proteins, for, the, treatment, of, cancers, with, 'Ras', mutations]), verbo([have]), complemento([been, elusive])]). relacion([sujeto(['The', need, thus, persists, for, therapies, to]), verbo([target]), complemento([and, suppress, the, hyperactive, 'K-Ras', mutant, proteins, to, normal, levels, of, activity])]). relacion([sujeto(['The', potential, for, 'PCAIs', to, serve, as]), verbo([targeted]), complemento([anticancer, agents, for, pancreatic, cancer, was, evaluated, in, pancreatic, ductal, adenocarcinoma, '(', 'PDAC)', cell, lines, expressing, mutant, '(', 'MIAPaCa-2', and, 'Panc-1)', and, wild, type, '(', 'BxPC-3)', 'K-Ras', proteins])]). relacion([sujeto(['The', 'PCAIs']), verbo([inhibited]), complemento(['MIAPaCa-2', and, 'BxPC-3', cell, viability, and, induced, apoptosis, with, 'EC50', values, as, low, as, 1.9, µM])]). relacion([sujeto(['The', 'PCAIs,', at, 0.5, 'µM,']), verbo([inhibited]), complemento(['MIAPaCa-2', cell, migration, by, 50, '%', ',', inhibited, colony, formation, and, disrupted, 'F-actin', filament, organization])]). relacion([sujeto(['These', results]), verbo([reveal]), complemento([that, the, 'PCAIs', disrupt, pertinent, biological, processes, that, lead, to, pancreatic, cancer, progression, and, thus, have, the, potential, to, act, as, targeted, effective, treatments, for, pancreatic, cancer])]). relacion([sujeto(['Tongxinluo', '(', 'TXL),', a, traditional, 'Chinese', 'medicine,', can, ameliorate, neointimal, formation, via]), verbo([suppressing]), complemento([vascular, inflammatory, response, induced, by, vascular, injury])]). relacion([sujeto(['The', aim, of, present, study, was, to, examine, whether, the, expression, and, 'post-translational', modification, of, 'KLF5', were]), verbo([involved]), complemento([in, the, vasoprotective, effects, of, 'TXL'])]). relacion([sujeto(['In', 'vivo,', 'TXL']), verbo([inhibited]), complemento([neointimal, formation, induced, by, carotid, artery, injury])]). relacion([sujeto(['In', 'vitro,', 'TNF-α', treatment, of, macrophages, resulted, in, the]), verbo([increased]), complemento([proliferation, and, 'migration,', but, the, effects, of, 'TNF-α', on, macrophages, were, blocked, by, 'TXL', treatment])]). relacion([sujeto(['Intimal', hyperplasia, was, strongly, reduced, in, 'macrophage-specific', 'KLF5', knockout, '(', 'KLF5(ly-/-))', 'mice,', indicating, that, 'TXL']), verbo([inhibits]), complemento([intimal, hyperplasia, by, suppression, of, 'KLF5', expression])]). relacion([sujeto(['Furthermore,', besides, 'down-regulating', 'KLF5', expression, in, 'macrophages,', 'TXL', also]), verbo([regulated]), complemento(['KLF5', stability, by, ubiquitination, and, sumoylation, of, 'KLF5'])]). relacion([sujeto(['Finally,', 'TNF-α']), verbo([induced]), complemento(['KLF5', sumoylation, via, 'PI3K/Akt', 'signaling,', whereas, 'TXL', inhibited, 'Akt', phosphorylation, induced, by, 'TNF-α'])]). relacion([sujeto(['We', conclude, that, the, multiple, ingredients, in, 'TXL', may]), verbo([act]), complemento([on, different, 'targets,', which, in, turn, generates, a, range, of, actions, that, manifest, as, a, comprehensively, vasoprotective, effect])]). relacion([sujeto(['This', study, aimed, to, investigate, the, potential, molecular, mechanism, underlying, the, 'T3']), verbo([induced]), complemento([vascular, calcification, and, phenotype, transformation, of, vascular, smooth, muscle, cells, '(', 'VSMCs)'])]). relacion([sujeto(['When', compared, with, normal, control, 'group,', the, osteocalcin, 'content,', 'ALP', 'activity,', 'Osterix', and, 'Runx2', mRNA, expression, and, 'OPN', protein, expression]), verbo([increased]), complemento([significantly, '(', 'P<0'])]). relacion([sujeto(['When', compared, with, calcification, 'group,', 'Osterix', and, 'Runx2', mRNA, expression, and, 'OPN', protein, expression]), verbo([increased]), complemento([markedly, '(', 'P<0'])]). relacion([sujeto(['In', 'addition,', the, protein, expression, of, 'ERK1/2,', 'p-ERK,', 'Akt', and, 'p-Akt']), verbo([increased]), complemento([significantly, in, calcification, group])]). relacion([sujeto(['In', the, presence, of, integrin, 'αvβ3/ERK', blocker, '(', 'PD98059)', 'and/or', 'PI3K/Akt', antagonist, '(', 'LY294002),', 'T3', was, still, able, to]), verbo([inhibit]), complemento([the, 'calcification,', and, this, effect, was, similar, to, that, after, treatment, with, inhibitors, alone])]). relacion([sujeto(['T3', may]), verbo([act]), complemento([on, 'PI3K/Akt', signaling, pathway, to, inhibit, the, phenotype, transformation, of, 'VSMC,', which, then, suppresses, the, 'calcium/phosphate', induced, calcification, of, rat, 'VSMCs'])]). relacion([sujeto(['We', demonstrated, that, 'SphK1', is, highly]), verbo([expressed]), complemento([in, 'SK-NEP-1', and, 'G401', 'cells,', and, through, annexin, 'V/propidium', iodide, staining, and, flow, cytometry, 'analysis,', we, detected, cell, apoptosis])]). relacion([sujeto(['Treatment', with, 'SKI-5C']), verbo([inhibited]), complemento([proliferation, and, induced, apoptosis, of, 'SK-NEP-1', and, 'G401', cells, in, a, 'dose-dependent', manner])]). relacion([sujeto(['Moreover,', 'SKI-5C', treatment]), verbo([inhibited]), complemento([the, growth, of, 'SK-NEP-1', xenograft, tumors, in, nude, 'mice,', with, few, side, effects])]). relacion([sujeto(['Our', microarray, analysis, revealed, that, 'SKI-5C-treated', 'SK-NEP-1', cells, mostly, downregulated, 'PRKACA', and, significantly]), verbo([inhibited]), complemento([phosphorylation, of, 'ERK1/2', and, 'NF-κB', p65])]). relacion([sujeto(['These', results, imply, that, 'SKI-5C']), verbo([induces]), complemento([apoptosis, of, 'SK-NEP-1', cells, through, the, 'PRKACA/MAPK/NF-κB', pathway])]). relacion([sujeto(['While,', further, research, is]), verbo([required]), complemento([to, determine, the, underlying, 'details,', these, results, provide, new, clues, for, the, molecular, mechanism, of, cell, death, induced, by, 'SKI-5C', and, suggest, that, 'SKI-5C', may, act, as, new, candidate, drug, for, 'Wilms\'', tumor])]). relacion([sujeto(['Surrogate', markers, simple, enough, to, be, used, by, primary, care, workers]), verbo([have]), complemento([not, been, closely, investigated, by, the, community, experts, in, rural, 'Uttar', 'Pradesh'])]). relacion([sujeto(['Greater,']), verbo([targeted]), complemento([efforts, are, needed, to, identify, 'at-risk', elderly, people, living, in, the, community])]). relacion([sujeto(['These', predictors, would]), verbo([act]), complemento([as, surrogate, markers, and, can, be, easily, used, by, primary, care, workers, to, plan, and, provide, services, to, the, elderly, people, in, rural, communities])]). relacion([sujeto(['Techniques', to, reduce, abdominal, wall, surgical, 'trauma,', such, as, minilaparoscopy, and, needlescopic, 'graspers,', can, be, combined, effectively, in, colonic, 'resections,', and, may]), verbo([act]), complemento([synergistically, to, reduce, postoperative, pain, and, improve, outcomes])]). relacion([sujeto(['Research', over, the, past, decade]), verbo([suggested]), complemento([critical, roles, for, circular, 'RNAs', in, the, natural, growth, and, disease, progression])]). relacion([sujeto(['However,', it, remains, poorly, defined, whether, the, circular, 'RNAs']), verbo([participate]), complemento([in, 'Hirschsprung', disease, '(', 'HSCR)'])]). relacion([sujeto(['Here,', we]), verbo([reported]), complemento([that, the, 'cir-ZNF609', was, 'down-regulated', in, 'HSCR', compared, with, normal, bowel, tissues])]). relacion([sujeto(['Furthermore,', suppression, of, 'cir-ZNF609']), verbo([inhibited]), complemento([the, proliferation, and, migration, of, cells])]). relacion([sujeto(['Finally,', 'RNA', immunoprecipitation, and, luciferase, reporter, assays, demonstrated, that, 'cir-ZNF609', may]), verbo([act]), complemento([as, a, sponge, for, 'miR-150-5p', to, modulate, the, expression, of, 'AKT3'])]). relacion([sujeto(['Long', 'non-coding', 'RNAs', '(', 'lncRNAs)']), verbo([have]), complemento([been, implicated, in, pathogenesis, of, various, 'cancers,', including, lung, squamous, cell, carcinoma, '(', 'LUSC)', and, lung, adenocarcinoma, '(', 'LUAD)'])]). relacion([sujeto(['LncRNAs', that]), verbo([act]), complemento([as, oncogenes, and, 'lncRNA-regulating', transcription, factors, provide, novel, targets, for, 'anti-lung', cancer, therapeutics])]). relacion([sujeto(['The', questionnaire, revealed, a, substantial, amount, of, clinical, research, was, conducted, in, the, 'UK,', with, over, 200, veterinary, surgeons]), verbo([involved]), complemento([in, the, year, of, the, 'survey,', with, at, least, 170, academic, papers, involving, clinical, research, published, by, respondents, in, the, same, year])]). relacion([sujeto(['All', 'UK', veterinary, schools]), verbo([required]), complemento([ethical, review, of, clinical, research])]). relacion([sujeto(['The', oncogenic, transcription, factor, 'MYC', and, its]), verbo([binding]), complemento([partner, 'MAX', regulate, gene, expression, by, binding, to, 'DNA', at, 'enhancer-box', '(', 'E-box)', elements, 5, '\'', -, 'CACGTG-3\''])]). relacion([sujeto(['In', mammalian, 'genomes,', the, central, 'E-box', 'CpG']), verbo([has]), complemento([the, potential, to, be, methylated, at, the, 5, -, position, of, cytosine, '(', 5, 'mC),', or, to, undergo, further, oxidation, to, the, 5, -, hydroxymethyl, '(', 5, 'hmC),', 5, -, formyl, '(', 5, 'fC),', or, 5, -, carboxyl, '(', 5, 'caC)', forms])]). relacion([sujeto(['We']), verbo([find]), complemento([that, 'MAX', exhibits, the, greatest, affinity, for, a, 5, caC, or, unmodified, 'C-containing', 'E-box,', and, much, reduced, affinities, for, the, corresponding, 5, 'mC,', 5, hmC, or, 5, fC, forms])]). relacion([sujeto(['Crystallization', of, 'MAX', with, a, 5, caC, modified, 'E-box', oligonucleotide, revealed, that, 'MAX', 'Arg36']), verbo([recognizes]), complemento([5, caC, using, a, 5, 'caC-Arg-Guanine', 'triad,', with, the, next, nearest, residue, to, the, carboxylate, group, being, 'Arg60'])]). relacion([sujeto(['In', vitro]), verbo([binding]), complemento([studies, showed, that, whereas, mutation, of, 'Arg36', '(', 'R36W)', or, 'Arg35', '(', 'R35H/L)', completely, abolished, 'DNA', 'binding,', mutation, of, 'Arg60', '(', 'R60Q)', significantly, reduced, 'DNA', 'binding,', but, retained, a, preference, for, the, 5, caC, modified, 'E-box'])]). relacion([sujeto(['Together', these, data, indicate, that, 'MAX', can]), verbo([act]), complemento([as, a, direct, epigenetic, sensor, of, 'E-box', cytosine, modification, states, and, that, local, 'CpG', modification, and, 'MAX', variants, converge, to, modulate, the, 'MAX-MYC', transcriptional, network])]). relacion([sujeto(['However,', few, studies]), verbo([have]), complemento([explored, this, relation, in, breast, tissue])]). relacion([sujeto(['For', all, 'women,', a, negative, correlation, was]), verbo([found]), complemento([between, total, zinc, intakes, and, 'IL-10', '(', r, =, -, 0.26, ',', 'P', =])]). relacion([sujeto(['Our', findings]), verbo([suggest]), complemento([that, consumption, of, specific, 'antioxidants,', including, 'β-tocopherol,', 'zinc,', and, 'selenium,', may, act, on, the, breast, tissue, through, mechanisms, affecting, the, expression, of, some, inflammation, 'markers,', particularly, among, postmenopausal, women])]). relacion([sujeto(['In', 'fact,', some, studies]), verbo([have]), complemento([suggested, modifications, in, the, phosphorylation, status, of, key, enzymes, in, the, dark, compared, with, the, 'light,', or, when, photosynthesis, varies])]). relacion([sujeto(['We', show, that, 'light/dark,', 'CO2', and, 'O2', mole, fraction]), verbo([have]), complemento([differential, effects, on, enzyme, phosphorylation])]). relacion([sujeto(['Phosphorylation', events, that, appear, to, be, the, most, important, to]), verbo([regulate]), complemento([metabolite, contents, when, photosynthesis, varies, are, those, associated, with, sugar, and, pyruvate, 'metabolism:', sucrose, and, starch, synthesis, are, major, 'phosphorylation-controlled', steps, but, pyruvate, utilization, '(', by, phosphoenolpyruvate, carboxylase, and, pyruvate, 'dehydrogenase)', and, pyruvate, reformation, '(', by, pyruvate, orthophosphate, 'dikinase)', are, also, subjected, to, phosphorylation, control])]). relacion([sujeto(['PML']), verbo([nuclear]), complemento([bodies, '(', 'NBs)', are, accumulations, of, cellular, proteins, embedded, in, a, 'scaffold-like', structure, built, by, 'SUMO-modified', 'PML/TRIM19'])]). relacion([sujeto(['PML', and, other, 'NB', proteins]), verbo([act]), complemento([as, cellular, restriction, factors, against, human, cytomegalovirus, '(', 'HCMV),', 'however,', this, intrinsic, defense, is, counteracted, by, the, 'immediate-early', protein, 1, '(', 'IE1)', of, 'HCMV'])]). relacion([sujeto(['IE1', directly]), verbo([interacts]), complemento([with, the, 'PML', 'coiled-coil', domain, via, its, globular, core, region, and, disrupts, 'NB', foci, by, inducing, a, loss, of, 'PML', 'SUMOylation'])]). relacion([sujeto(['Here,', we, demonstrate, that, 'IE1']), verbo([acts]), complemento([via, abrogating, the, de, novo, 'SUMOylation', of, 'PML'])]). relacion([sujeto(['Interestingly,', we, observed, that, 'IE1', expression, did, not, affect, preSUMOylated, 'PML,', 'however,', it, clearly]), verbo([prevented]), complemento([de, novo, 'SUMO', conjugation])]). relacion([sujeto(['Furthermore,', 'IE1']), verbo([acts]), complemento([in, a, selective, manner, since, 'K160', was, identified, as, the, main, target, lysine])]). relacion([sujeto(['This', is, strengthened, by, the, fact, that, 'IE1', also]), verbo([prevents]), complemento(['As2O3-mediated', hyperSUMOylation, of, 'K160', thereby, blocking, 'PML', degradation])]). relacion([sujeto(['Since', 'IE1', did, not, interfere, with, 'coiled-coil']), verbo([mediated]), complemento(['PML', dimerization, we, propose, that, 'IE1', either, affects, 'PML', autoSUMOylation, by, directly, abrogating, 'PML', 'E3', ligase, function, or, by, preventing, the, access, to, 'SUMO', sites])]). relacion([sujeto(['Thus,', our, data]), verbo([suggest]), complemento([a, novel, mechanism, how, a, viral, protein, counteracts, a, cellular, restriction, factor, by, selectively, preventing, the, de, novo, 'SUMOylation', at, specific, lysine, residues, without, affecting, global, protein, 'SUMOylation'])]). relacion([sujeto(['The', human, cytomegalovirus, 'IE1', protein]), verbo([acts]), complemento([as, an, important, antagonist, of, a, cellular, restriction, mechanism, that, is, mediated, by, a, subnuclear, structure, termed, 'PML', nuclear, bodies])]). relacion([sujeto(['This', function, of, 'IE1', is]), verbo([required]), complemento([for, efficient, viral, replication, and, thus, constitutes, a, potential, target, for, antiviral, strategies])]). relacion([sujeto(['We', show, that, tight]), verbo([binding]), complemento([of, 'IE1', to, 'PML', interferes, with, the, de, novo, 'SUMOylation', of, a, distinct, lysine, residue, that, is, also, the, target, of, 'stress-mediated', hyperSUMOylation, of, 'PML'])]). relacion([sujeto(['Furthermore,', it, highlights, the, possibility, to, develop, small, molecules, that, specifically, abrogate, this, 'PML-antagonistic', activity, of, 'IE1', and, thus]), verbo([inhibit]), complemento([viral, replication])]). relacion([sujeto(['Strong', social, bonds, form, between, individuals, in, many, 'group-living', 'species,', and, these, relationships, can]), verbo([have]), complemento([important, fitness, benefits])]). relacion([sujeto(['When']), verbo([responding]), complemento([to, vocalizations, produced, by, 'groupmates,', receivers, are, expected, to, adjust, their, behaviour, depending, on, the, nature, of, the, bond, they, share, with, the, signaller])]). relacion([sujeto(['Using', 'field-based', playback, experiments, on, a, habituated, population, of, wild, dwarf, mongooses, '(', 'Helogale', 'parvula),', we, first, demonstrate, that, a, particular, vocalization, given, on, detecting, predatory, snakes, does]), verbo([act]), complemento([as, a, recruitment, 'call;', receivers, were, more, likely, to, 'look,', approach, and, engage, in, mobbing, behaviour, than, in, response, to, control, close, calls])]). relacion([sujeto(['We', then, show, that, individuals]), verbo([respond]), complemento([more, strongly, to, these, recruitment, calls, if, they, are, from, groupmates, with, whom, they, are, more, strongly, bonded, '(', those, with, whom, they, preferentially, groom, and, 'forage)'])]). relacion([sujeto(['Our', 'study,', 'therefore,']), verbo([provides]), complemento([novel, evidence, about, the, 'anti-predator', benefits, of, close, bonds, within, social, groups])]). relacion([sujeto(['How', species, will]), verbo([respond]), complemento([to, these, changes, depends, on, their, capacity, for, plastic, and, adaptive, responses])]). relacion([sujeto(['We']), verbo([found]), complemento([that, 'multi-generational', exposure, to, warming, alone, caused, an, increase, 'in:', juvenile, developmental, 'rate,', reactive, oxygen, species, production, and, mitochondrial, density, and, decreases, 'in:', average, reproductive, body, 'size,', fecundity, and, fluctuations, in, mitochondrial, 'capacity,', relative, to, control, conditions])]). relacion([sujeto(['Remarkably,', when, both, drivers, of, global, change, were, 'present,', only, mitochondrial, capacity, was, significantly, 'affected,']), verbo([suggesting]), complemento([that, ocean, warming, and, acidification, act, as, opposing, vectors, of, stress, across, multiple, generations])]). relacion([sujeto(['Methylglyoxal', is, detoxified, by, the, 'Glyoxalase', 'system,', consisting, of, two, 'enzymes,', 'Glo1', and, 'Glo2,', that]), verbo([act]), complemento([sequentially, to, convert, 'MG', into, 'D-lactate'])]). relacion([sujeto(['Recently,', the, 'Parkinsonism-associated', protein, 'DJ-1', was, described, in, vitro, to]), verbo([have]), complemento([glyoxalase, 'activity,', thereby, detoxifying, the, 'MG', 'metabolite,', or, deglycase, 'activity,', thereby, removing, the, adduct, formed, by, 'MG', on, proteins])]). relacion([sujeto(['Furthermore,', we]), verbo([provide]), complemento([data, suggesting, that, the, previously, reported, deglycation, activity, of, 'DJ-1', can, be, ascribed, to, a, 'TRIS', buffer, artefact])]). relacion([sujeto(['In', this, 'study,', we, '(', 1, ')', collected, morphological, data, on, the, bristles, of, 23, species, of, 'Mymaridae', by, analyzing, 'high-resolution', photographs, and, '(', 2, ')', used, the, immersed, boundary, method, to, determine, via, numerical, simulation, whether, bristled, wings, reduced, the, force]), verbo([required]), complemento([to, fling, the, wings, apart, while, still, maintaining, lift])]). relacion([sujeto(['In', the, morphological, 'study,', we]), verbo([found]), complemento([that, as, the, body, length, of, 'Mymaridae', 'decreases,', the, diameter, and, gap, between, bristles, decreases, and, the, percentage, of, the, wing, area, covered, by, bristles, increases])]). relacion([sujeto(['In', the, numerical, 'study,', we]), verbo([found]), complemento([that, a, bristled, wing, experiences, less, force, than, a, solid, wing])]). relacion([sujeto(['The']), verbo([decrease]), complemento([in, force, with, increasing, gap, to, diameter, ratio, is, greater, at, higher, angles, of, attack, than, at, lower, angles, of, 'attack,', suggesting, that, bristled, wings, may, act, more, like, solid, wings, at, lower, angles, of, attack, than, they, do, at, higher, angles, of, attack])]). relacion([sujeto(['In', 'wing-wing', 'interactions,', bristled, wings, significantly]), verbo([decrease]), complemento([the, drag, required, to, fling, two, wings, apart, compared, with, solid, 'wings,', especially, at, lower, 'Reynolds', numbers])]). relacion([sujeto(['Baicalin', and, scutellarin, are, similar, in, structure, except, scutellarin]), verbo([has]), complemento([an, additional, hydroxyl, at, composition, 'C-4\''])]). relacion([sujeto(['In', this, 'work,', we, observed, that, baicalin, and, scutellarin]), verbo([promoted]), complemento([glucose, disposal, in, mice, and, in, adipocytes])]). relacion([sujeto(['Baicalin', selectively]), verbo([increased]), complemento([phosphorylation, of, 'AMP-activated', kinase, '(', 'AMPK),', while, scutellarin, selectively, enhanced, 'Akt', phosphorylation])]). relacion([sujeto(['Both', of, them]), verbo([increased]), complemento(['AS160', phosphorylation, and, glucose, uptake, in, basal, condition])]). relacion([sujeto(['In', 'contrast,', 'Akt', inhibitor, and, knockdown, of, 'Akt', with, siRNA]), verbo([decreased]), complemento(['scutellarin-stimulated', glucose, uptake, but, had, no, effects, on, baicalin])]). relacion([sujeto(['The', molecular, dynamic, simulations, analysis, showed, that, the]), verbo([binding]), complemento([energy, of, baicalin, to, 'AMPK', '(', -, 34.3, 'kcal/mol)', was, more, favorable, than, scutellarin, '(', -, 21.27, 'kcal/mol),', while, the, binding, energy, of, scutellarin, '(', -, 29.81, 'kcal/mol)', to, 'Akt', was, much, more, favorable, than, baicalin, '(', 4.04, 'kcal/mol)'])]). relacion([sujeto(['Interestingly,', a, combined, treatment, with, baicalin, and, scutellarin]), verbo([act]), complemento([synergistically, to, enhance, glucose, uptake, in, adipocytes, '(', combination, 'index:', 0.94, -, 0.046, ')'])]). relacion([sujeto(['In', 'conclusion,', baicalin, and, 'scutellarin,', though, structurally, 'similar,']), verbo([promoted]), complemento([glucose, disposal, in, adipocytes, by, differential, regulation, on, 'AMPK', and, 'Akt', activity])]). relacion([sujeto(['Our', data]), verbo([provide]), complemento([insight, that, multicomponent, herbal, medicines, may, act, synergistically, and, cooperatively, on, multiple, targets])]). relacion([sujeto(['Supra/interspinous', ligaments, connect, adjacent, spinous, processes, and]), verbo([act]), complemento([as, a, stabilizer, of, the, spine])]). relacion([sujeto(['However,', few]), verbo([report]), complemento([have, discussed, ossification, 'supra/interspinous', ligaments, '(', 'OSIL),', so, its, epidemiology, remains, unknown])]). relacion([sujeto(['The', sum, of, the, levels]), verbo([involved]), complemento([by, 'OPLL', '(', 'OP-index)', and, 'OSIL', '(', 'OSI-index)', as, well, as, the, prevalence, of, ossification, of, the, nuchal, ligament, '(', 'ONL)', were, also, investigated])]). relacion([sujeto(['We']), verbo([found]), complemento([a, significant, positive, correlation, between, the, 'OP-index', grade, and, 'OSI-index'])]). relacion([sujeto(['Rapid', response, team, '(', 'RRT)', responders, would, benefit, from, 'training,', to]), verbo([ensure]), complemento([competent, and, efficient, management, of, the, deteriorating, patient])]). relacion([sujeto(['Responses', were, 'positive,', with, 79.8, '%', of, responses, '(', 912, /, 1143, ')', agreeing, that, the, participants, had, learnt, something, 'new,', that, the, course, would]), verbo([increase]), complemento([their, confidence, and, competence, during, 'RRT', 'calls,', and, that, it, had, assisted, them, as, an, educator])]). relacion([sujeto(['There', was, unanimous, agreement, by, participants, for, further, development, of, a, formalised, 'RRT', training, course, for]), verbo([responding]), complemento([to, the, deteriorating, patient])]). relacion([sujeto(['Interest']), verbo([has]), complemento([slowly, waned, for, 'ACT', implementation])]). relacion([sujeto(['This', review, highlights, the, evidence, for, 'ACT', to, improve, general, medical, 'outcomes,', reduce, treatment, 'costs,', and]), verbo([increase]), complemento([access, to, treatment])]). relacion([sujeto(['No', studies]), verbo([reported]), complemento([on, clinical, outcomes, of, general, medical, comorbidities, or, on, mortality, of, 'ACT', clients])]). relacion([sujeto(['Half', of, the, studies]), verbo([reporting]), complemento([utilization, '(', three, of, 'six)', found, a, decrease, in, emergency, room, 'usage,', and, three, of, four, studies, identified, an, increase, in, outpatient, primary, care, visits])]). relacion([sujeto(['Most', studies]), verbo([found]), complemento([no, increase, in, overall, medical, care, costs])]). relacion([sujeto(['Of', the, few, studies]), verbo([reporting]), complemento([on, quality, of, 'life,', most, found, mild, to, moderate, improvements])]). relacion([sujeto(['To', 'date,', rigorous, scientific, examination, of, the, effect, of, 'ACT', on, the, general, health, of, the, populations, it, serves]), verbo([has]), complemento([not, been, undertaken])]). relacion([sujeto(['Snails', of, the, genus, 'Biomphalaria']), verbo([act]), complemento([as, intermediate, host, for, 'S'])]). relacion([sujeto(['Biomphalaria', straminea, is, not, indigenous, in, 'China', but, was, accidentally, introduced, to, 'Hong', 'Kong', from, 'South', 'America', and]), verbo([has]), complemento([spread, to, other, habitats, in, the, southern, parts, of, the, country])]). relacion([sujeto(['In', this, 'connection,', although, no, such, infection]), verbo([has]), complemento([been, recorded, in, the, field, so, 'far,', the, continuous, expansion, of, 'China\'s', projects, in, endemic, areas, of, 'Africa', and, import, of, the, infection, via, returning, workers, or, visitors, deserve, attention])]). relacion([sujeto(['Risk', areas, were]), verbo([found]), complemento([in, southeastern, 'China', and, it, is, expected, that, they, will, guide, policies, and, control, programmes, to, potential, areas, area, of, snail, abundance, and, used, for, spatial, targeting, of, control, interventions, for, this, invasive, species])]). relacion([sujeto(['Fragile', 'X', syndrome, '(', 'FXS)', is, the, most, common, form, of, familial, mental, retardation, and, one, of, the]), verbo([leading]), complemento([known, causes, of, autism])]). relacion([sujeto(['Leptin', may, be, considered, a, 'cytokine-like', hormone, with, pleiotropic, actions, since, it, may, be]), verbo([involved]), complemento([in, the, regulation, of, neuroendocrine, functions, and, the, immune, system, 'response,', in, addition, to, playing, a, role, in, development])]). relacion([sujeto(['Leptin', and, adiponectin, may]), verbo([act]), complemento([in, parallel, as, opposing, metabolic, counterparts])]). relacion([sujeto(['Adiponectin', levels, in, 'FXS', patients, were, significantly, lower, than, those]), verbo([found]), complemento([in, controls, '(', p, &, 'lt;', 0.04, ')'])]). relacion([sujeto(['Leptin', levels, in, 'FXS', patients, were, significantly, higher, than, those]), verbo([found]), complemento([in, controls, '(', p, =, 0.03, ')'])]). relacion([sujeto(['Adipokines', may, be]), verbo([involved]), complemento([in, the, psychiatric, features, observed, in, 'FXS', patients])]). relacion([sujeto(['Attaching', polar, pharmacological, modifiers, to, molecular, imaging, probes, is, a, common, strategy, to]), verbo([modulate]), complemento([their, pharmacokinetic, profiles, to, improve, such, parameters, as, the, clearance, rate, of, radiotracers, 'and/or', 'metabolites,', and, to, enhance, 'signal-to-background', ratios])]). relacion([sujeto(['Control', experiments]), verbo([suggest]), complemento([that, this, may, be, the, result, of, unspecific, accumulation, of, metabolites, in, which, the, glucuronic, acid, moiety, does, not, act, as, an, innocent, pharmacological, modifier])]). relacion([sujeto(['Recent', studies, in, tropical, alpine, environments, demonstrated, how, pioneer, plant, species, defined, as, &, 'quot;ecosystem', 'engineers"', are, capable, of]), verbo([enhancing]), complemento(['landscape-level', richness, by, adding, new, species, to, the, community, through, the, modification, of, 'microhabitats,', and, also, provided, hints, about, the, alternation, of, different, ecosystem, engineers, over, time])]). relacion([sujeto(['Focusing', on, the, altitudinal, limit, of, 'Peruvian', 'Dry', 'Puna', 'vegetation,', we, hypothesized, that, positive, interactions, structure, plant, communities, by, facilitation, cascades]), verbo([involving]), complemento([different, ecosystem, 'engineers,', determining, the, evolution, of, the, microhabitat, patches, in, terms, of, abiotic, resources, and, beneficiary, species, hosted])]). relacion([sujeto([nitrogen, and, organic, matter, 'content,', and, 'temperature),', was, the, main, driver, of, species, assemblage, at, the, community, 'scale,']), verbo([enhancing]), complemento([species, richness])]). relacion([sujeto(['Cushion', plants]), verbo([act]), complemento([as, 'pioneers,', by, starting, the, successional, processes, that, continue, with, shrubs, and, tussocks])]). relacion([sujeto(['Tussock', grasses]), verbo([have]), complemento([sometimes, been, found, to, be, capable, of, creating, microhabitat, patches, independently])]). relacion([sujeto(['The', dynamics, of, species, assemblage, seem, to, follow, the, nested, assemblage, 'mechanism,', in, which, the, first, foundation, species, to, colonize, a, habitat]), verbo([provides]), complemento([a, novel, substrate, for, colonization, by, other, foundation, species, through, a, facilitation, cascade, process])]). relacion([sujeto(['American', pikas, '(', 'Ochotona', 'princeps)']), verbo([have]), complemento([been, heralded, as, indicators, of, 'montane-mammal', response, to, contemporary, climate, change])]). relacion([sujeto(['Conversely,', pikas]), verbo([have]), complemento([exhibited, higher, rates, of, occupancy, and, persistence, in, 'Rocky', 'Mountain', and, 'Sierra', 'Nevada', montane, '\'', 'mainlands\''])]). relacion([sujeto(['Research', and, monitoring, efforts, on, pikas, across, the, western, 'USA']), verbo([have]), complemento([collectively, shown, the, nuance, and, complexity, with, which, climate, will, often, act, on, species, in, diverse, topographic, and, climatic, contexts])]). relacion([sujeto(['However,', to, date, no, studies]), verbo([have]), complemento([investigated, 'habitat,', 'distribution,', and, abundance, of, pikas, across, hundreds, of, sites, within, a, remote, wilderness, area])]). relacion([sujeto(['Additionally,', relatively, little, is, known, about, whether, climate]), verbo([acts]), complemento([most, strongly, on, pikas, through, direct, or, indirect, '(', e])]). relacion([sujeto(['During', 2007, -, 2009, ',', we, collectively, hiked, &, 'gt;16,000', km, throughout, the, 410, ',', 77, -]), verbo([ha]), complemento(['Glacier', 'National', 'Park,', 'Montana,', 'USA,', in, an, effort, to, identify, 'topographic,', 'microrefugial,', and, vegetative, characteristics, predictive, of, pika, abundance])]). relacion([sujeto(['Ranking', of, alternative, 'logistic-regression', models, based, on, 'AICc', scores, revealed, that, 'short-term', pika, abundances, were, positively]), verbo([associated]), complemento([with, intermediate, 'elevations,', greater, cover, of, 'mosses,', and, taller, 'forbs,', and, decreased, each, 'year,', for, a, total, decline, of, 68, '%', during, the, 'three-year', 'study;', whereas, 'longer-term', abundances, were, associated, only, with, static, variables, '(', 'longitude,', 'elevation,', 'gradient)', and, were, lower, on, 'north-facing', slopes])]). relacion([sujeto(['not)', were]), verbo([associated]), complemento([with, lower, observed, pika, abundance])]). relacion([sujeto(['Limited', studies]), verbo([have]), complemento([been, conducted, to, examine, the, issue, of, patient, access, to, spine, surgeons, based, on, different, insurance, types, '(', 'Medicaid', vs])]). relacion([sujeto(['The', waiting, period, was, studied, in, the, context, of, comparing, states, that]), verbo([have]), complemento([expanded, 'Medicaid', eligibility, to, ones, that, have, 'not,', and, the, surgical, training, of, the, spine, surgeon, '(', orthopaedic, surgeons, vs])]). relacion([sujeto(['Overall,', this, study]), verbo([suggests]), complemento([that, increased, coverage, resulting, from, 'Medicaid', expansion, does, not, necessarily, equate, to, increased, access, to, care])]). relacion([sujeto(['Competitive', endogenous, 'RNAs', '(', 'ceRNAs)']), verbo([act]), complemento([as, molecular, sponges, for, microRNAs, '(', 'miRNAs),', and, are, associated, with, tumorigenesis, in, various, 'cancers,', including, laryngeal, cancer, '(', 'LC)'])]). relacion([sujeto(['In', 'IceNet,', ceRNAs]), verbo([targeting]), complemento(['inflammation-related', genes, tended, to, be, network, hubs])]). relacion([sujeto(['Gene', 'Ontology', and, 'Kyoto', 'Encyclopedia', of, 'Genes', and, 'Genomes', pathway, analyses, indicated, that, 'IceNet', molecules, are]), verbo([associated]), complemento([with, multiple, 'cancer-related', functions, and, signaling, pathways])]). relacion([sujeto(['This', 18, -, mRNA, and, 'one-lncRNA', module]), verbo([provides]), complemento([a, novel, mechanism, for, potentially, improving, 'LC', patient, prognostic, predictions])]). relacion([sujeto(['Frequent']), verbo([loss]), complemento([of, multiple, regions, in, short, arm, of, chromosome, 3, is, found, in, various, tumors, including, gastric, cancer, '(', 'GC)'])]). relacion([sujeto(['RNA']), verbo([binding]), complemento(['motif,', 'single-stranded', interacting, protein, 3, '(', 'RBMS3)', is, a, tumor, suppressor, gene, located, in, this, region, and, mediates, cancer, angiogenesis])]). relacion([sujeto(['We']), verbo([found]), complemento([that, 'RBMS3', level, was, 'decreased,', whereas, 'HIF1A', was, elevated, in, 'GC'])]). relacion([sujeto(['Furthermore,', we, demonstrated, that, 'RBMS3', was, an, independent, prognostic, factor, and, the, levels, of, 'RBMS3', and, 'HIF1A', were]), verbo([associated]), complemento([with, 'GC', angiogenesis, and, histopathological, 'differentiation:', patients, with, lower, 'RBMS3', level, and, higher, nuclear, 'HIF1A', expression, had, poorer, prognosis])]). relacion([sujeto(['These', findings, implicated, that, 'RBMS3', and]), verbo([nuclear]), complemento(['HIF1A', could, act, as, prognostic, biomarkers, and, therapeutic, targets, for, 'GC'])]). relacion([sujeto(['Raf', kinase, inhibitor, protein, '(', 'RKIP)']), verbo([has]), complemento([been, shown, to, be, a, suppressor, of, the, 'mitogen-activated', protein, kinase, pathway, and, is, reported, to, be, involved, in, human, malignancy])]). relacion([sujeto(['However,', the, molecular, mechanism, of, hepatitis, 'B', virus, '(', 'HBV)', in]), verbo([regulating]), complemento(['RKIP', expression, is, not, yet, clarified])]). relacion([sujeto(['Among', seven, 'HBV-encoded', 'proteins,', we]), verbo([found]), complemento(['HBV', 'X', '(', 'HBX)', protein, could, significantly, inhibit, the, expression, level, of, 'RKIP,', indicating, that, 'HBV', could, suppress, 'RKIP', expression, through, regulating, 'HBX'])]). relacion([sujeto(['Our', results, showed, that, 'HBX', can]), verbo([interact]), complemento([with, 'AP1', protein, to, inhibit, the, 'RKIP', transcription])]). relacion([sujeto(['Moreover,', we, observed, that, the, promoter, methylation, level, of, 'RKIP', could, be]), verbo([enhanced]), complemento([by, 'HBV'])]). relacion([sujeto(['In', 'conclusion,', our, study, revealed, that, 'RKIP', could]), verbo([act]), complemento([as, a, molecular, marker, for, 'HBV-infected', liver, 'cancer,', but, had, no, 'tumor-suppressing', effect])]). relacion([sujeto(['Autophagy', is, a, tightly]), verbo([regulated]), complemento([catabolic, process, that, leads, to, the, degradation, of, cytoplasmatic, components, such, as, 'aggregated/misfolded', proteins, and, organelles, through, the, lysosomal, machinery])]). relacion([sujeto(['Recent', studies]), verbo([suggest]), complemento([that, autophagy, plays, such, a, role, in, the, context, of, the, 'anti-tumor', immune, 'response,', make, it, an, attractive, target, for, cancer, immunotherapy])]). relacion([sujeto(['In', blood, cancer, 'cells,', autophagy, can, either, result, in, chemoresistance, or]), verbo([induce]), complemento([autophagic, cell, death, that, may, act, as, immunogenic])]). relacion([sujeto(['Loss', of, the, genes, depletes, the, 'cell\'s', reserve, of, antitoxin, and, allows, the, toxin, to]), verbo([act]), complemento([upon, the, cell])]). relacion([sujeto(['PSK', benefits, mobile, elements, when, it]), verbo([increases]), complemento([reproductive, success, relative, to, other, mobile, competitors])]). relacion([sujeto(['Most', 'PSK', systems, use, a, cytoplasmic, 'toxin,', but, the, external, toxins, of, bacteriocins, also]), verbo([have]), complemento([a, 'PSK-like', effect])]). relacion([sujeto(['The', secreted, ribonuclease, barnase, and, its, protein, inhibitor, barstar]), verbo([have]), complemento([features, in, common, with, 'PSK', 'modules,', though, their, native, context, is, chromosomal])]). relacion([sujeto(['However,', barnase, toxicity, did, not, occur, under, the, conditions, 'tested,']), verbo([suggesting]), complemento([that, barnase, is, toxic, to, neighbouring, cells, only, under, very, specific, conditions])]). relacion([sujeto(['Bacteriocins', are, only, produced, under, some, 'conditions,', and, some, conditionality, on, toxin, function, or]), verbo([release]), complemento([may, be, advantageous, in, general, to, 'PSKs', with, external, toxins, because, it, would, prevent, killing, of, potential, 'plasmid-naïve', hosts])]). relacion([sujeto(['Too', much, 'conditionality,', 'however,', would, limit, how, advantageous, the, gene, pair, was, to, mobile, 'elements,', making, the, genes, unlikely, to, be]), verbo([recruited]), complemento([as, a, 'PSK', system])]). relacion([sujeto(['Diadenosine', polyphosphates, '(', 'ApnA)', are, thought, to]), verbo([act]), complemento([as, signaling, molecules, regulating, stress, responses, and, biofilm, formation, in, prokaryotes])]). relacion([sujeto(['In', both, 'wild-type', and, apaH, mutant, cells, cultured, on, starvation, medium, '(', 'CF', 'agar),', the, levels, of, intracellular, diadenosine, tetraphosphate, '(', 'Ap4A)', and, pentaphosphate, '(', 'Ap5A)']), verbo([increased]), complemento([several, fold, during, the, first, 16, h, of, 'development,', and, decreased, gradually, thereafter])]). relacion([sujeto(['ApnA', hydrolase, activity, of, the, 'wild-type', strain]), verbo([increased]), complemento([1.5, -, fold, during, the, first, 8, h, of, 'development,', and, then, gradually, decreased])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([the, possibility, that, high, intracellular, levels, of, 'Ap4A', 'and/or', 'Ap5A', may, inhibit, 'M'])]). relacion([sujeto(['Pyriculol', was, isolated, from, the, rice, blast, fungus, 'Magnaporthe', oryzae, and]), verbo([found]), complemento([to, induce, lesion, formation, on, rice, leaves])]). relacion([sujeto(['These', findings]), verbo([suggest]), complemento([that, it, could, be, involved, in, virulence])]). relacion([sujeto(['Inactivation', of, a, putative, 'oxidase-encoding', gene, 'MoC19OXR1,', which, was]), verbo([found]), complemento([to, be, located, in, the, genome, close, to, 'MoPKS19,', resulted, in, a, mutant, exclusively, producing, dihydro, pyriculol, and, 'Dihydro', pyriculariol])]). relacion([sujeto(['The', 'MoPKS19', 'cluster,', 'furthermore,', comprises, two, transcription, factors, 'MoC19TRF1', and, 'MoC19TRF2,', which, were, both]), verbo([found]), complemento([individually, to, act, as, negative, regulators, repressing, gene, expression, of, 'MoPKS19'])]). relacion([sujeto(['Additionally,', extracts, of, 'ΔMopks19', and, 'ΔMoC19OXR1', made, from, axenic, cultures, failed, to]), verbo([induce]), complemento([lesions, on, rice, leaves, compared, to, extracts, of, the, wild, type, strain])]). relacion([sujeto(['Consequently,', pyriculol, and, its, isomer, pyriculariol, appear, to, be, the, only, lesion]), verbo([inducing]), complemento([secondary, metabolites, produced, by, 'MoWT', under, these, culture, conditions])]). relacion([sujeto(['Interestingly,', the, mutants, unable, to, produce, pyriculol, and, pyriculariol, were, as, pathogenic, as, 'MoWT,', demonstrating, that, pyriculol, is, not]), verbo([required]), complemento([for, infection])]). relacion([sujeto(['Guidance', issued, by, the, 'Nursing', and, 'Midwifery', 'Council', '(', 'NMC)', clearly, states, that, nurses, who]), verbo([act]), complemento([in, an, unprofessional, or, unlawful, way, on, social, media, put, their, registration, at, risk])]). relacion([sujeto(['The', announcement, of, nursing, degree, apprenticeships]), verbo([has]), complemento([been, criticised, as, an, '\'', act, of, 'amnesia\'', by, a, leading, nurse, professor])]). relacion([sujeto(['The', 'Mental', 'Capacity', 'Act', 2005, was, enacted, with, the, aim, of, improving, the, protection]), verbo([provided]), complemento([by, the, law, to, the, most, vulnerable, people, in, society])]). relacion([sujeto(['The', principles, of, the]), verbo([act]), complemento([specify, to, whom, the, act, can, be, 'applied,', and, how, to, ensure, these, individuals, are, placed, at, the, centre, of, 'decision-making', about, their, treatment, and, care])]). relacion([sujeto(['Appropriate', application, of, the]), verbo([act]), complemento([should, ensure, all, treatment, and, care, planned, for, vulnerable, people, is, in, those, 'individuals\'', best, interests])]). relacion([sujeto(['A', 'best-interests', decision]), verbo([involves]), complemento([considering, the, 'person\'s', past, and, current, written, and, spoken, 'wishes,', listening, carefully, to, those, close, to, the, individual, and, being, aware, of, biases, that, might, influence, the, consultation, process])]). relacion([sujeto(['Nurses']), verbo([have]), complemento([an, important, role, in, this, process, because, of, their, unique, position, in, the, healthcare, team])]). relacion([sujeto(['This', extension]), verbo([provides]), complemento([us, the, time, necessary, to, take, all, of, the, administrative, actions, we, need, to, take, in, order, to, reinstate, uniform, use, of, medical, and, psychological, consultants])]). relacion([sujeto(['An']), verbo([increasing]), complemento([number, of, studies, show, bactericidal, activity, of, natural, treatments, in, aquaculture])]). relacion([sujeto(['Colloidal', silver, gave, a, 'MIC', of, 2, mg, 'ml-1,', and, the, inhibitory, halos, were]), verbo([found]), complemento([to, be, between, 11.8, and, 18.8, 'mm,', depending, on, treatment, concentrations])]). relacion([sujeto(['An', in, vivo, challenge, test, was, conducted, on, white, shrimp, postlarvae, cultured, at, low, salinity, '(', 5, practical, salinity, 'units,', 'PSU),', and, a, significant]), verbo([increase]), complemento(['(', p, &, 'lt;', 0.05, ')', in, survival, was, demonstrated, in, the, presence, of, the, aqueous, extracts, '(', oregano, 64, '%', ',', neem, 76, '%', and, colloidal, silver, 90, '%', ')', ',', when, compared, to, the, control, '(', 0, '%', ')', in, the, challenge, test])]). relacion([sujeto(['However,', no, significant, differences, were, observed, between, 'treatments,']), verbo([suggesting]), complemento([that, they, all, act, as, alternative, bactericidal, source, agents, against, 'V'])]). relacion([sujeto(['Totally,', 16, controlled, trials, '(', 1898, 'cases)']), verbo([involving]), complemento([angiogenesis, inhibitors, plus, chemotherapy, '(', 'ACT', 'group)', versus, chemotherapy, alone, group, '(', 'CT', 'group)', were, identified, from, 'PubMed,', 'EMBASE,', 'Cochrane', 'Library', and, 'Wanfang', 'Data', before, 'March', 2016])]). relacion([sujeto(['Remarkably,', subgroup, analysis, showed, that, the, antibodies]), verbo([targeting]), complemento(['VEGF', significantly, prolonged, 'PFS', '(', 'HR', =, 0.76, ;, 95, '%', 'CI', =, 0.64, -, 0.9, ;, 'P', =, 0.001, ')'])]). relacion([sujeto(['Compared', with, chemotherapy, 'alone,', antibodies]), verbo([targeting]), complemento(['VEGF', plus, chemotherapy, significantly, improved, 'ORR', and, prolonged, 'PFS', with, an, acceptable, toxicity, profile, for, patients, with, 'SCLC'])]). relacion([sujeto(['Therefore,', angiogenesis, 'inhibitors,', especially, antibodies]), verbo([targeting]), complemento(['VEGF,', combining, with, chemotherapy, may, be, a, potential, promising, strategy, in, managing, 'SCLC'])]). relacion([sujeto(['The']), verbo([increase]), complemento([in, geomagnetic, activity, '(', 'GMA),', radio, and, 'X-ray', fluxes, and, solar, 'X-ray', flares, were, negatively, correlated, with, cell, numbers])]). relacion([sujeto(['Cell']), verbo([losses]), complemento([were, observed, in, the, short, 'experiment,', but, not, in, the, longest, one])]). relacion([sujeto(['The', differential, action, windows, might, be, indicative, of, two, differential, disruptive, 'mechanisms:', 'EMR', might]), verbo([act]), complemento([on, 'DNA', synthesis, and, mitosis, phases, of, the, cell, cycle, '(', taking, place, in, the, dark, 'period)', and, 'GMA', might, be, more, disruptive, at, the, end, of, mytosis, or, cytokinesis, phases, taking, place, in, the, light, period])]). relacion([sujeto(['Formation', of, long, chains, '(', &, 'gt;', 4, 'cells/chain)', was, reduced, with, salinity, and, with, temperatures, above, 27, º, 'C', but]), verbo([increased]), complemento([with, 'EMR', and, 'GMA,', particularly, when, grown, at, the, highest, temperatures, recorded, during, the, study, period, '(', '≥28ºC)'])]). relacion([sujeto(['However,', this, relationship]), verbo([has]), complemento([been, little, evaluated, across, stages, of, hyperglycemia, and, for, a, broad, range, of, common, mental, disorders, '(', 'CMDs)'])]). relacion([sujeto(['Cross-sectional', study, conducted, among, civil, servants, aged, 35, -, 74, years]), verbo([participating]), complemento([in, the, 'ELSA-Brasil', cohort])]). relacion([sujeto(['For', individuals, with, previously, known, diabetes, and, newly, classified, 'diabetes,', for, every, 1, '%']), verbo([increase]), complemento([in, 'HbA1c,', the, prevalence, of, depressive, disorders, 'became,', 'respectively,', 12, '%', and, 23, '%', greater, '(', 'PR:', 1.12, ;, 95, '%', 'CI:', 1.0, -, 1.26, ;, and, 'PR:', 1.23, ;, 95, '%', 'CI:', 1.04, -, 1.44, ')'])]). relacion([sujeto(['No', relationship, between, intermediate, hyperglycemia, and, 'CMDs', was, 'observed,', thus]), verbo([suggesting]), complemento([that, causal, processes, relating, to, 'CMDs,', if, 'present,', must, act, more, proximally, to, diabetes, onset])]). relacion([sujeto(['Amino', 'ester-based', 'benzene-1,3,5-tricarboxamides', '(', 'BTAs)', are, widely, studied, experimentally, for, their, facile, 'self-assembly,', which]), verbo([leads]), complemento([to, strong, 'three-fold', hydrogen, bonded, supramolecular, polymers])]). relacion([sujeto(['AA', dimers, form, three, hydrogen, bonds, between, the, two, 'molecules,', are, typical, of, 'BTA', 'stacks,', and]), verbo([act]), complemento([as, a, basic, building, block, of, assembly])]). relacion([sujeto(['We']), verbo([find]), complemento([that, at, zero, 'Kelvin,', the, 'AC', dimer, is, more, stable, than, the, 'AA', dimer, by, roughly, 20, kcal, 'mol(-1)'])]). relacion([sujeto(['The', 'PIM', family, of, 'serine/threonine', kinases]), verbo([has]), complemento([three, highly, conserved, isoforms, '(', 'PIM1,', 'PIM2', and, 'PIM3)'])]). relacion([sujeto(['PIM', proteins, are]), verbo([regulated]), complemento([through, transcription, and, stability, by, 'JAK/STAT', pathways, and, are, overexpressed, in, hematological, malignancies, and, solid, tumors])]). relacion([sujeto(['The', 'PIM', kinases, possess, weak, oncogenic, 'abilities,', but]), verbo([enhance]), complemento([other, genes, or, chemical, carcinogens, to, induce, tumors])]). relacion([sujeto(['We']), verbo([found]), complemento([an, increase, in, alterations, of, sexual, organs, and, hyperplasia, in, the, transgenic, mice, correlating, with, inflammation])]). relacion([sujeto(['We', also]), verbo([found]), complemento([that, 'PIM1/2', are, overexpressed, in, a, subset, of, human, male, germ, cells, and, prostate, tumors, correlating, with, inflammatory, features, and, stem, cell, markers])]). relacion([sujeto(['Our', data]), verbo([suggest]), complemento([that, 'PIM1/2', kinase, overexpression, is, a, common, feature, of, male, reproductive, organs, 'tumors,', which, provoke, tissue, alterations, and, a, large, inflammatory, response, that, may, act, synergistically, during, the, process, of, tumorigenesis])]). relacion([sujeto(['There', is, also, a, correlation, with, markers, of, cancer, stem, 'cells,', which, may, contribute, to, the, therapy, resistance]), verbo([found]), complemento([in, tumors, overexpressing, 'PIM', kinases])]). relacion([sujeto(['Here', we, show, that, disorder, in, the, form, of, random, gauge, fields, that]), verbo([act]), complemento([directly, on, particle, phases, can, also, drive, localization])]). relacion([sujeto(['Netrins,', a, family, of, 'laminin-related', 'molecules,']), verbo([have]), complemento([been, proposed, to, act, as, guidance, cues, either, during, nervous, system, development, or, the, establishment, of, the, vascular, system])]). relacion([sujeto(['Here,', we, present, the, 'high-resolution', structure, of, 'netrin-4,', which, shows, unique, features, in, comparison, with, 'netrin-1,', and, show, that, it, does, not]), verbo([bind]), complemento([directly, to, any, of, the, known, 'netrin-1', receptors])]). relacion([sujeto(['We', show, that, 'netrin-4', disrupts, laminin, networks, and, basement, membranes, '(', 'BMs)', through, 'high-affinity']), verbo([binding]), complemento([to, the, laminin, γ1, chain])]). relacion([sujeto(['It', is, necessary, to]), verbo([increase]), complemento([our, knowledge, in, this, field, to, improve, the, quality, of, care, and, social, support, for, this, vulnerable, group, of, patients])]). relacion([sujeto(['The', main]), verbo([finding]), complemento([indicated, that, participants, experienced, frustration, and, discrimination, because, they, were, required, to, provide, sexual, partners, with, information, about, their, 'HIV', 'status,', which, is, compulsory, under, the, 'Swedish', 'Disease', 'Act'])]). relacion([sujeto(['The', 'HIV-positive', migrants, appreciated, the, free, access, to, antiviral, 'therapy,', but, wished, to]), verbo([have]), complemento([more, time, for, 'patient-physician', communications])]). relacion([sujeto(['One', quarter, of, gay, or, bisexual, men, and, half, of, lesbian, or, bisexual, women]), verbo([have]), complemento(['children,', compared, with, 90, '%', of, heterosexual, women, and, 'men,', which, means, 'LGBT', older, adults, are, more, likely, to, reside, in, care, homes])]). relacion([sujeto(['Older', 'LGBT', people, may, be, unwilling, to]), verbo([express]), complemento([their, sexual, identities, in, care, settings, and, this, can, affect, their, care])]). relacion([sujeto(['Members', of, older, 'people\'s', informal, care, networks, must, be, recognised, to]), verbo([ensure]), complemento([their, involvement, in, the, lives, of, residents, in, care, settings, continues])]). relacion([sujeto(['To', the, best, of, the, 'knowledge,', there]), verbo([have]), complemento([been, no, studies, related, to, the, 'intra-articular', injection, of, methotrexate, '(', 'Met)-loaded', 'click-cross-linkable', 'SIS', '(', 'Met-loaded', 'Cx-SIS)', for, 'RA', treatment])]). relacion([sujeto(['The', formed, 'Cx-SIS', depot, is]), verbo([maintained]), complemento([in, the, articular, joint, over, an, extended, 'period,', while, 'SIS', alone, rapidly, disappears])]). relacion([sujeto(['Collectively,', these, results, indicate, that, the, 'Met-loaded', 'Cx-SIS', depot, is, successfully, formed, after, 'intra-articular', injection, of, 'click-cross-linkable', 'SIS,', and, that, this, formulation]), verbo([induces]), complemento(['long-lasting', 'Met', release, and, allows, 'Met', to, act, effectively, in, the, articular, 'joint,', resulting, in, 'RA', repair])]). relacion([sujeto(['When', grown, on, copper, 'supports,', these, films]), verbo([have]), complemento([preferred, orientation, of, the, constituent, 'crystallites,', translating, into, markedly, different, wetting, properties, of, the, 'film\'s', two, surfaces, '(', 'water-pinning', vs])]). relacion([sujeto(['In', 'addition,', the, films, exhibit, differential, sorption, of, various, organic, 'solvents,', can, recover, oil, spills, from, 'seawater,', and, can, also]), verbo([act]), complemento([as, active, layers, of, chemical, sensors])]). relacion([sujeto(['This', study]), verbo([reports]), complemento([for, the, first, time, that, compounds, of, 'Ge', '(', 'II)', can, function, as, superbases])]). relacion([sujeto(['These', 'DFT', calculations, showed, better, agreement, of, geometrical, parameters, for, the]), verbo([reported]), complemento([stable, germylene, compound, 1, than, previously, reported, calculations, at, the, 'B3LYP/6-31G(2d,p)', and, 'PBE/DZP', level, of, theory])]). relacion([sujeto(['The', 'σ-donating', substituents, attached, to, the, 'Ge', '(', 'II)', center]), verbo([enhance]), complemento([the, basicity, to, a, much, higher, extent, compared, to, the, combination, of, π, and, 'σ-donor', substituents])]). relacion([sujeto(['The', stabilities, of, these, designed, superbases]), verbo([have]), complemento([been, examined, with, dimerization, energy, and, 'singlet-triplet', state, energy, difference, '(', '∆ES-T)'])]). relacion([sujeto(['The', energetics, for, the, reaction, with, 'BH3', and, 'AlMe3', further]), verbo([suggest]), complemento([that, the, lone, pair, of, 'Ge', '(', 'II)', can, act, as, a, 'Lewis', base, and, display, higher, 'donor-acceptor', bond, strengths])]). relacion([sujeto(['Vacuolar', processing, enzymes, '(', 'VPEs)', are, cysteine, proteinases, that]), verbo([act]), complemento([as, crucial, mediators, of, programmed, cell, death, '(', 'PCD)', in, plants])]). relacion([sujeto(['Survival', rate, and, chlorophyll, retention, analyses, showed, that, suppression, of, 'OsVPE3', clearly]), verbo([enhanced]), complemento([salt, stress, tolerance, in, transgenic, rice, compared, with, wild, type])]). relacion([sujeto(['Furthermore,', fragmentation, of, genomic, 'DNA', was]), verbo([inhibited]), complemento([in, plants, with, 'down-regulated', 'OsVPE3'])]). relacion([sujeto(['Notably,', overexpression, of, 'OsVPE3']), verbo([promoted]), complemento([vacuole, 'rupture,', whereas, suppression, of, 'OsVPE3', attenuated, or, delayed, the, disintegration, of, vacuolar, membranes])]). relacion([sujeto(['Moreover,', we]), verbo([found]), complemento([that, suppression, of, 'OsVPE3', caused, decreased, leaf, width, and, guard, cell, length, in, rice])]). relacion([sujeto(['Taken', 'together,', these, results, indicated, that, suppression, of, 'OsVPE3']), verbo([enhances]), complemento([salt, tolerance, by, attenuating, vacuole, rupture, during, 'PCD'])]). relacion([sujeto(['Many']), verbo([reports]), complemento([document, a, common, perception, of, colors, as, more, 'saturated,', with, increased, brightness, and, contrast, in, the, environment, '(', &, 'quot;Visual', 'Intensifications")'])]). relacion([sujeto(['This', wide, assortment, of, visual, phenomena]), verbo([suggests]), complemento([that, one, single, neuropsychopharmacological, mechanism, is, unlikely, to, explain, such, vast, phenomenological, diversity])]). relacion([sujeto(['Starting', with, mechanisms, that]), verbo([act]), complemento([at, the, cellular, 'level,', the, key, role, of, 5, -, 'HT2A', receptor, activation, and, the, subsequent, increased, cortical, excitation, will, be, considered])]). relacion([sujeto(['Next,', it, will, be, shown, that, area, specific, anatomical, and, dynamical, features, link]), verbo([increased]), complemento([excitation, to, the, specific, visual, contents, of, hallucinations])]). relacion([sujeto(['The']), verbo([decrease]), complemento([of, alpha, oscillations, by, hallucinogens, will, then, be, introduced, as, a, systemic, mechanism, for, amplifying, 'internal-driven', excitation, that, overwhelms, 'stimulus-induced', excitations])]). relacion([sujeto(['Finally,', the, 'hallucinogen-induced', parallel]), verbo([decrease]), complemento([of, the, 'N170', visual, evoked, potential, and, increased, medial, 'P1', potential, will, be, discussed, as, key, mechanisms, for, inducing, a, dysbalance, between, global, integration, and, early, visual, gain, that, may, explain, several, 'hallucinogen-induced', visual, 'experiences,', including, visual, 'hallucinations,', 'illusions,', and, intensifications])]). relacion([sujeto(['Findings', also, highlight, the, ways, in, which, providers]), verbo([act]), complemento([to, reinforce, and, subvert, these, policies, while, mitigating, risk, in, this, service, setting])]). relacion([sujeto(['Recommendations', for]), verbo([enhancing]), complemento([the, recovery, orientation, of, supportive, housing, and, implications, for, the, design, of, the, homeless, service, system, are, discussed])]). relacion([sujeto(['Epac', proteins, are]), verbo([involved]), complemento([in, the, regulation, of, several, physiological, processes])]). relacion([sujeto(['In', particular, 'Epac1']), verbo([mediates]), complemento([the, regulation, of, molecular, processes, underlying, cell, adhesion, and, mobility])]). relacion([sujeto(['In', the, pancreas, activation, of, 'Epac2', potentiates, the]), verbo([release]), complemento([of, 'glucose-induced', insulin, secretion, and, received, attention, as, a, putative, target, for, antidiabetic, treatment])]). relacion([sujeto(['While', the, regulation, of, 'Epac', by, cAMP]), verbo([has]), complemento([been, analysed, in, structural, and, biochemical, 'detail,', less, is, known, on, the, interaction, of, 'Epac', with, 'non-canonical', cyclic, nucleotides])]). relacion([sujeto(['This', chapter, will, discuss, to, what, extent, other, cyclic, purines, than, cAMP, or, cyclic, pyrimidine, could]), verbo([act]), complemento([as, 'Epac', agonists, or, antagonists])]). relacion([sujeto(['Prolactin', treatment, of, adult, female, mice, for, a, period, equivalent, to, pregnancy, and, the, first, week, of, lactation]), verbo([increased]), complemento([immune, cell, flux, through, the, mammary, 'gland,', as, reflected, in, the, number, of, immune, cells, in, mammary, 'gland-draining,', but, not, other, lymph, nodes])]). relacion([sujeto(['Prolactin', did, not]), verbo([act]), complemento([as, a, direct, 'chemo-attractant,', but, through, effects, on, luminal, mammary, epithelial, 'cells,', increased, the, 'chemo-attractant', properties, of, conditioned, medium])]). relacion([sujeto(['Depletion', of, 'CCL2', and, 'CXCL1', from, conditioned, medium, reduced, 'chemo-attraction', of, monocytes, and, 'neutrophils,', and, prolactin]), verbo([increased]), complemento([expression, of, these, two, chemokines, in, mammary, epithelial, cells])]). relacion([sujeto(['We', conclude, that, prolactin, is, an, important, player, in, the, recruitment, of, immune, cells, to, the, mammary, gland, both, through, its, activities, to]), verbo([increase]), complemento([epithelial, cell, number, as, well, as, production, of, 'chemo-attractants', on, a, per, cell, basis])]). relacion([sujeto(['Several', lines, of, evidence]), verbo([suggest]), complemento([that, pituitary, adenylate, 'cyclase-activating', polypeptide, '(', 'PACAP)', is, a, neuropeptide, playing, an, important, role, as, a, neuromodulator])]). relacion([sujeto(['It']), verbo([has]), complemento([been, indicated, that, 'PACAP', is, associated, with, mental, 'diseases,', and, that, regulation, of, the, 'PACAPergic', signals, could, be, a, potential, target, for, the, treatment, of, such, psychiatric, states, as, schizophrenia])]). relacion([sujeto(['Recent', studies]), verbo([have]), complemento([suggested, that, action, of, neuroleptic, drugs, is, mediated, not, only, by, dopaminergic, and, serotonergic, 'neurotransmission,', but, also, via, neuropeptides, which, may, act, both, as, neurotransmitters, and, as, neuromodulators])]). relacion([sujeto(['PAC1', mRNA, expression, fell, after, 24, -, h, incubation, with, haloperidol, or, 'olanzapine;', however, the, effect, was, not]), verbo([maintained]), complemento([after, 72, &, 'nbsp;h,', and, haloperidol, even, 'up-regulated', 'PAC1', mRNA, expression, in, a, 'dose-dependent', manner])]). relacion([sujeto(['All', the, examined, drugs]), verbo([decreased]), complemento(['VPAC2', mRNA, 'expression,', especially, after, 72, -, h, incubation])]). relacion([sujeto(['In', 'addition,', 'PACAP']), verbo([increased]), complemento(['PAC1', and, 'VPAC2', mRNA, expression])]). relacion([sujeto(['In', 'conclusion,', our, findings]), verbo([suggest]), complemento(['PACAP', receptors, may, be, involved, in, the, mechanism, of, typical, and, atypical, neuroleptic, drugs])]). relacion([sujeto(['The', study, of, enzyme, function, often]), verbo([involves]), complemento([a, 'multi-disciplinary', approach])]). relacion([sujeto(['Additionally,', structures, can, be, used, to]), verbo([modulate]), complemento([or, improve, functional, activity, of, enzymes, by, the, production, of, small, molecules, that, act, as, 'substrates/cofactors', or, by, engineering, selected, mutants, with, enhanced, biological, activity])]). relacion([sujeto(['Results', indicated, that, traxoprodil, potentiated, activity, of, all, antidepressants, examined, in, 'FST', and, the, observed, effects, were, not, due, to, the]), verbo([increase]), complemento([in, locomotor, activity])]). relacion([sujeto(['Only', in, the, case, of, 'co-administration', of, traxoprodil, and, 'bupropion,']), verbo([increased]), complemento([bupropion, concentrations, in, brain, tissue, were, observed])]). relacion([sujeto(['All', tested, agents]), verbo([increased]), complemento([the, traxoprodil, levels, in, the, brain])]). relacion([sujeto(['Administration', of, a, 'sub-active', dose, of, traxoprodil, with, antidepressants, from, different, chemical, 'groups,', which]), verbo([act]), complemento([via, enhancing, monoaminergic, 'transduction,', caused, the, 'antidepressant-like', effect, in, 'FST', in, mice])]). relacion([sujeto(['Diverse', molecules]), verbo([mediate]), complemento(['cross-kingdom', communication, between, bacteria, and, their, eukaryotic, partners, and, determine, pathogenic, or, symbiotic, relationships])]). relacion([sujeto(['N-acyl-L-homoserine', 'lactone-dependent', 'quorum-sensing', signaling, represses, the, biosynthesis, of, bacterial, cyclodipeptides, '(', 'CDPs)', that]), verbo([act]), complemento([as, auxin, signal, mimics, in, the, host, plant, 'Arabidopsis', thaliana])]). relacion([sujeto(['In', this, 'work,', we, performed, 'bioinformatics,', 'biochemical,', and, plant, growth, analyses, to, identify, 'non-ribosomal', peptide, synthase, '(', 'NRPS)', proteins, of, 'Pseudomonas', 'aeruginosa,', which, are]), verbo([involved]), complemento([in, 'CDP', synthesis])]). relacion([sujeto(['When', analyzing, the, bioactivity, of, 'purified,', naturally, produced, 'CDPs,', it, was]), verbo([found]), complemento([that, 'cyclo(L-Pro-L-Tyr)', and, 'cyclo(L-Pro-L-Val)', were, capable, of, antagonizing, 'quorum-sensing-LasR', '(', 'QS-LasR)-dependent', signaling, in, a, contrasting, manner, in, the, 'cell-free', supernatants, of, the, selected, 'NRPS', 'mutants,', which, showed, 'QS', induction])]). relacion([sujeto(['The', results, indicate, that, although, relatively, high, levels, of, 'return-to-sport', outcomes, were, achieved, at, 24, months, compared, with, those, previously]), verbo([reported]), complemento([in, the, 'literature,', correlations, between, objective, clinical, tests, and, 'return-to-sport', outcomes, may, not, occur])]). relacion([sujeto(['Clinical', outcome, measures, may]), verbo([provide]), complemento([suitable, baseline, 'information;', 'however,', the, results, of, this, study, suggest, that, clinicians, may, need, to, place, greater, emphasis, on, other, outcome, measures, when, seeking, to, objectively, promote, safe, return, to, sport])]). relacion([sujeto(['MicroRNA', '(', 'miR)-133b']), verbo([has]), complemento([been, reported, to, act, as, a, tumor, suppressor, in, multiple, types, of, human, 'cancers,', including, non, small, cell, lung, cancer, '(', 'NSCLC)'])]). relacion([sujeto(['However,', the, underlying, mechanism, by, which, 'miR-133b']), verbo([inhibits]), complemento(['NSCLC', metastasis, remains, largely, unclear])]). relacion([sujeto(['The', expression, level, of, 'miR-133b', was]), verbo([found]), complemento([to, be, significantly, downregulated, in, 'NSCLC', cell, lines, compared, with, normal, lung, epithelial, 'BEAS-2B', cells])]). relacion([sujeto(['Further', investigation, identified, fascin1, '(', 'FSCN1)', as, a, direct]), verbo([target]), complemento([of, 'miR-133b', in, 'NSCLC', cells])]). relacion([sujeto(['The', expression, of, 'FSCN1', was, significantly]), verbo([increased]), complemento([in, 'NSCLC', cell, lines, compared, with, 'BEAS-2B', 'cells,', and, its, protein, expression, was, negatively, regulated, by, 'miR-133b', in, 'NSCLC', 'A549', cells])]). relacion([sujeto(['Further', investigation, showed, that, the, upregulation, of, 'miR-133b', notably]), verbo([inhibited]), complemento(['NSCLC', cell, migration, and, 'invasion,', while, the, overexpression, of, 'FSCN1', significantly, promoted, 'NSCLC', cell, migration, and, invasion])]). relacion([sujeto(['Accordingly,', the, present, study]), verbo([suggests]), complemento([that, 'miR-133b', inhibits, the, migration, and, invasion, of, 'NSCLC', cells, via, directly, targeting, 'FSCN1,', and, thus, may, be, used, for, the, treatment, of, 'NSCLC', metastasis])]). relacion([sujeto(['Ubenimex,', an, aminopeptidase, 'N', 'inhibitor,', is, widely, used, as, an, adjunct, therapy, after, surgery, to]), verbo([enhance]), complemento([the, function, of, immunocompetent, cells, and, confer, antitumor, effects])]). relacion([sujeto(['Our', previous, study, demonstrated, that, ubenimex]), verbo([induces]), complemento([autophagic, cell, death, in, 'RCC', cells])]). relacion([sujeto(['Recently,', the, molecular, mechanism, of, autophagy, induction]), verbo([has]), complemento([been, associated, with, radiosensitivity, in, 'RCC', cells])]). relacion([sujeto(['In', the, present, 'study,', the, ability, of, ubenimex, to]), verbo([enhance]), complemento(['RCC', cell, sensitivity, to, radiation, via, the, induction, of, autophagic, cell, death, was, 'determined,', and, the, mechanism, of, action, of, this, effect, was, investigated])]). relacion([sujeto(['The', 'AO-EB', staining, and, flow, cytometry, of, the, 'OS-RC-2', cells, indicated, that, the, combined, treatment, significantly]), verbo([enhanced]), complemento([autophagic, cell, death, compared, with, ubenimex, or, 'IR', alone])]). relacion([sujeto(['Therefore,', treatment, with, ubenimex, did, not, significantly, alter, cell, cycle, progression, but]), verbo([increased]), complemento([cell, death, when, combined, with, radiation])]). relacion([sujeto(['An', 'Akt', agonist, could, significantly, weaken, this, 'effect,', indicating, that, ubenimex, may]), verbo([act]), complemento([as, an, 'Akt', inhibitor])]). relacion([sujeto(['Furthermore,', the, western, blot, analysis, indicated, that, the, combined, treatment]), verbo([inhibited]), complemento([the, 'Akt', signaling, pathway, compared, with, ubenimex, treatment, or, 'IR', alone])]). relacion([sujeto(['Ubenimex', may]), verbo([enhance]), complemento(['RCC', cell, sensitivity, to, radiation, by, inducing, cell, autophagy])]). relacion([sujeto(['This', induction, changes, the, role, of, autophagy, from, protective, to, lethal, in, 'vitro,', and, this, switch, is]), verbo([associated]), complemento([with, the, inhibition, of, the, 'Akt', signaling, pathway])]). relacion([sujeto(['Exposure', to, environmental, 'chemicals,', such, as, 'dioxin,', is, known, to]), verbo([have]), complemento([adverse, effects, on, the, homeostasis, of, gonadal, 'steroids,', thereby, potentially, altering, the, sexual, differentiation, of, the, brain, to, express, autistic, traits])]). relacion([sujeto(['Dioxin-like', chemicals]), verbo([act]), complemento([on, the, aryl, hydrocarbon, receptor, '(', 'AhR),', 'polymorphisms,', and, mutations, of, 'AhR-related', gene, may, exert, pathological, influences, on, sexual, differentiation, of, the, 'brain,', causing, autistic, traits])]). relacion([sujeto(['Although', no, statistically, significant, difference, was]), verbo([found]), complemento([between, autism, spectrum, disorder, '(', 'ASD)', patients, and, control, individuals, for, the, genotypic, distribution, of, any, of, the, polymorphisms, studied, 'herein,', a, significant, difference, in, the, total, score, of, severity, was, observed, in, rs2228099, 'polymorphism,', suggesting, that, the, polymorphism, modifies, the, severity, of, 'ASD', symptoms, but, not, 'ASD', susceptibility])]). relacion([sujeto(['Moreover,', we]), verbo([found]), complemento([that, a, significant, difference, in, the, social, communication, score, of, severity, was, observed])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, the, rs2228099, polymorphism, is, possibly, associated, with, the, severity, of, social, communication, impairment, among, the, diverse, 'ASD', symptoms])]). relacion([sujeto(['Arginine', and, 'Glutamate-Rich', protein, 1, '(', 'ARGLU1)', is, a, protein, whose, function, is, poorly, 'understood,', but, may]), verbo([act]), complemento([in, both, transcription, and, 'pre-mRNA', splicing])]). relacion([sujeto(['We', demonstrate, that, the, 'ARGLU1', gene]), verbo([expresses]), complemento([at, least, three, distinct, 'RNA', splice, isoforms, -, a, fully, spliced, isoform, coding, for, the, 'protein,', an, isoform, containing, a, retained, intron, that, is, detained, in, the, 'nucleus,', and, an, isoform, containing, an, alternative, exon, that, targets, the, transcript, for, nonsense, mediated, decay])]). relacion([sujeto(['Furthermore,', 'ARGLU1', contains, a, 'long,', highly, evolutionarily]), verbo([conserved]), complemento([sequence, known, as, an, 'Ultraconserved', 'Element', '(', 'UCE)', that, is, within, the, retained, intron, and, overlaps, the, alternative, exon])]). relacion([sujeto(['Further,', overexpression, of, the, 'ARGLU1', protein, shifted, the, splicing, of, endogenous, 'ARGLU1', 'mRNA,', resulting, in, an]), verbo([increase]), complemento([in, the, retained, intron, isoform, and, nonsense, mediated, decay, susceptible, isoform, and, a, decrease, in, the, fully, spliced, isoform])]). relacion([sujeto(['Taken', together, with, data, showing, that, functional, protein, knockout, shifts, splicing, toward, the, fully, spliced, 'isoform,', our, data, are, consistent, with, a, model, in, which, unproductive, splicing, complexes, assembled, at, the, alternative, exon]), verbo([lead]), complemento([to, inefficient, splicing, and, intron, retention])]). relacion([sujeto(['Unplanned', extubations, can]), verbo([lead]), complemento([to, iatrogenic, injury, and, have, the, potential, to, contribute, to, serious, safety, events])]). relacion([sujeto(['A', voice, of, the, customer, survey, ascertained, perceptions, regarding, unplanned, extubation]), verbo([causes]), complemento([and, impact, on, care])]). relacion([sujeto(['Descriptive', statistics, were, used, to]), verbo([report]), complemento([survey, results])]). relacion([sujeto(['We', noted, a, statistically, significant]), verbo([decrease]), complemento([in, the, number, of, intubated, days, between, the, 'pre-', and, 'post-improvement', groups, '(', 'P', &, 'lt;'])]). relacion([sujeto(['Staff', underestimated, the, prevalence, of, unplanned, extubations, but]), verbo([recognized]), complemento([the, need, for, improvement])]). relacion([sujeto(['The']), verbo([decrease]), complemento([in, intubated, days, may, have, been, a, 'by-product', of, the, 'post-improvement', phase, 'improvements,', which, encouraged, practice, changes])]). relacion([sujeto(['While', international, research, shows, that, receipt, of, welfare, benefits, is]), verbo([associated]), complemento([with, poor, mental, 'health,', less, is, known, about, the, relationship, between, welfare, receipt, and, mental, health, service, use])]). relacion([sujeto(['We', investigate, whether, 'within-person', change, in, welfare, recipient, status, is]), verbo([associated]), complemento([with, change, in, mental, health, service, use])]). relacion([sujeto(['Individuals', were, more, likely, to]), verbo([report]), complemento([greater, mental, health, service, use, at, times, of, welfare, receipt])]). relacion([sujeto(['The']), verbo([increase]), complemento([in, mental, health, service, use, associated, with, a, transition, onto, welfare, benefits, was, much, greater, than, the, decline, in, service, use, associated, with, the, transition, off, benefits])]). relacion([sujeto(['Within', 'individuals,', welfare, receipt, is]), verbo([associated]), complemento([with, greater, mental, health, service, use])]). relacion([sujeto(['The', extracellular, loops, '(', 'ECLs)', of, 'G', 'protein-coupled', receptors, '(', 'GPCRs)', can]), verbo([bind]), complemento([directly, to, docked, orthosteric, or, allosteric, 'ligands,', they, can, contain, transient, contact, points, for, ligand, entry, into, the, transmembrane, '(', 'TM)', bundle, and, they, can, regulate, the, activation, of, the, receptor, signalling, pathways])]). relacion([sujeto(['This']), verbo([has]), complemento([been, shown, through, biochemical, techniques, and, has, been, supported, by, the, many, subsequent, crystal, structures, of, 'GPCRs', bound, to, both, agonists, and, antagonists])]). relacion([sujeto(['ECL2', shares, common, structural, features, between, '(', and, sometimes, 'across)', receptor, 'sub-families', and, can, facilitate, ligand, entry, to, the, 'TM', core, or]), verbo([act]), complemento([directly, as, a, surface, of, the, 'ligand-binding', pocket])]). relacion([sujeto(['Structural', similarities, seem, to, underpin, common]), verbo([binding]), complemento(['mechanisms;', 'however,', where, these, 'exist,', variations, in, primary, sequence, ensure, 'ligand-binding', specificity])]). relacion([sujeto(['Increasing', evidences]), verbo([have]), complemento([demonstrated, that, the, dysregulation, of, long, 'non-coding', 'RNAs', '(', 'lncRNAs)', may, act, as, an, important, role, in, tumor, progression])]). relacion([sujeto(['The', long, 'non-coding', 'RNA', 'SPRY4', intronic, transcript, 1, '(', 'SPRY4-IT1)']), verbo([has]), complemento([been, reported, in, some, cancer, including, regulating, cell, 'growth,', 'differentiation,', 'apoptosis,', and, cancer, progression])]). relacion([sujeto(['We']), verbo([found]), complemento([that, 'SPRY4-IT1', was, 'up-regulated', in, 'HCC', cell, lines])]). relacion([sujeto(['Further', function, analysis, demonstrated, that, knockdown, of, 'SPRY4-IT1', significantly]), verbo([inhibited]), complemento(['HCC', cells, proliferation, and, 'invasion,', but, 'over-expression', of, 'SPRY4-IT1', had, the, opposite, effects, on, 'HCC', cells, in, vitro])]). relacion([sujeto(['Moreover,', our, results, also, indicated, that, 'SPRY4-IT1', 'over-expression', significantly]), verbo([promoted]), complemento([the, 'epithelial-mesenchymal', transition, '(', 'EMT)', by, 'up-regulating', the, transcription, factor, 'Twist1', and, 'EMT', marker, 'Vimentin', and, inhibited, the, 'E-cadherin', expression, in, 'MHCC97L', cell])]). relacion([sujeto(['Whereas,', knockdown, of, 'SPRY4-IT1']), verbo([suppressed]), complemento([the, transcription, factor, 'Twist1', and, 'EMT', marker, 'Vimentin', and, increased, the, 'E-cadherin', expression, in, 'MHCC97H', cells])]). relacion([sujeto(['Mechanisms', investigations, showed, that, 'SPRY4-IT1']), verbo([interacted]), complemento([with, the, 'EZH2', and, epigenetically, repressed, the, 'E-cadherin', expression])]). relacion([sujeto(['In', 'vivo,', we, also, demonstrated, that, the, tumor, growth, was]), verbo([inhibited]), complemento([in, 'SPRY4-IT1', knockdown, group, compared, with, the, control, group])]). relacion([sujeto(['These', results]), verbo([suggested]), complemento([that, lncRNA, 'SPRY4-IT1', might, be, considered, as, a, therapeutic, target, in, 'HCC'])]). relacion([sujeto(['As', regards, causal, 'factors,', a, review, of, the, confabulation, literature]), verbo([suggests]), complemento([that, neither, amnesia, nor, executive, impairment, can, be, the, sole, '(', or, perhaps, even, the, 'primary)', cause, of, all, delusional, beliefs, -, though, they, may, act, in, concert, with, other, factors])]). relacion([sujeto(['A', key, perspective, in, the, modern, literature, is, that, many, delusions]), verbo([have]), complemento([an, emotionally, positive, or, '\'', 'wishful\'', 'element,', that, may, serve, to, modulate, or, manage, emotional, experience])]). relacion([sujeto(['Some', authors]), verbo([have]), complemento([referred, to, this, perspective, as, the, '\'', emotion, 'dysregulation\'', hypothesis])]). relacion([sujeto(['In', this, article, we, review, the, theoretical, underpinnings, of, this, 'approach,', and, develop, the, idea, by]), verbo([suggesting]), complemento([that, the, positive, aspects, of, confabulatory, states, may, have, a, role, in, perpetuating, the, imbalance, between, cognitive, control, and, emotion])]). relacion([sujeto(['These', findings]), verbo([suggest]), complemento([that, the, emotions, that, we, want, to, feel, '(', or, do, not, want, to, 'feel)', can, influence, the, way, we, reconstruct, past, experiences, and, generate, a, sense, of, self, -, a, proposition, that, bears, on, a, unified, theory, of, delusional, belief, states])]). relacion([sujeto(['To', address, this, we]), verbo([have]), complemento([developed, a, massively, parallel, sequencing, targeted, 'DSD', gene, panel, which, allows, us, to, sequence, all, 64, known, diagnostic, 'DSD', genes, and, candidate, genes, simultaneously])]). relacion([sujeto(['We', analyzed, 'DNA', from, the, largest]), verbo([reported]), complemento([international, cohort, of, patients, with, 'DSD', '(', 278, patients, with, 46, ',', 'XY', 'DSD', and, 48, with, 46, ',', 'XX', 'DSD)'])]). relacion([sujeto(['Our']), verbo([targeted]), complemento([gene, panel, compares, favorably, with, other, sequencing, platforms])]). relacion([sujeto(['We']), verbo([found]), complemento([a, total, of, 28, diagnostic, genes, that, are, implicated, in, 'DSD,', highlighting, the, genetic, spectrum, of, this, disorder])]). relacion([sujeto(['In', many, cases, our, findings, are, informative, as, to, the, likely]), verbo([cause]), complemento([of, the, 'DSD,', which, will, facilitate, clinical, management])]). relacion([sujeto(['Our', massively, parallel, sequencing]), verbo([targeted]), complemento(['DSD', gene, panel, represents, an, economical, means, of, improving, the, genetic, diagnostic, capability, for, patients, affected, by, 'DSD'])]). relacion([sujeto(['Implementation', of, this, panel, in, a, large, cohort, of, patients]), verbo([has]), complemento([expanded, our, understanding, of, the, underlying, genetic, etiology, of, 'DSD'])]). relacion([sujeto(['The', inclusion, of, research, candidate, genes, also]), verbo([provides]), complemento([an, invaluable, resource, for, future, identification, of, novel, genes])]). relacion([sujeto(['The', aim, of, this]), verbo([report]), complemento([was, to, assess, the, added, benefit, of, the, drug, combination, dolutegravir, /, abacavir, /, lamivudine, '(', 'DTG', /, 'ABC', /, 3, 'TC)', compared, with, the, appropriate, comparator, therapy, '(', 'ACT)', in, adults, and, adolescents, above, 12, years, of, age, infected, with, human, immunodeficiency, virus, '(', 'HIV)'])]). relacion([sujeto(['The', aim, of, this]), verbo([report]), complemento([was, to, assess, the, added, benefit, of, aflibercept, in, comparison, with, ranibizumab, or, grid, laser, therapy, as, appropriate, comparator, therapy, '(', 'ACT)', in, adult, patients, with, visual, impairment, due, to, macular, oedema, following, branch, retinal, vein, occlusion, '(', 'BRVO)'])]). relacion([sujeto(['The', assessment, was, conducted, based, on, 'patient-relevant', outcomes, and, on, the, data]), verbo([provided]), complemento([by, the, company, in, the, dossier])]). relacion([sujeto(['The', aim, of, the, present]), verbo([report]), complemento([is, to, assess, the, added, benefit, of, apremilast, in, comparison, with, adalimumab, or, infliximab, or, ustekinumab, as, appropriate, comparator, therapy, '(', 'ACT)', in, adult, patients, with, moderate, to, severe, chronic, plaque, psoriasis, who, failed, to, respond, to, or, who, have, a, contraindication, 'to,', or, are, intolerant, to, other, systemic, therapy, including, 'cyclosporine,', methotrexate, or, psoralen, and, 'ultraviolet-A', light, '(', 'PUVA)'])]). relacion([sujeto(['The', aim, of, the, present]), verbo([report]), complemento([was, to, assess, the, added, benefit, of, dulaglutide, for, the, treatment, of, adults, with, type, 2, diabetes, mellitus, in, comparison, with, the, appropriate, comparator, therapy, '(', 'ACT)', specified, by, the, 'Federal', 'Joint', 'Committee', '(', 'G-BA)'])]). relacion([sujeto(['The', assessment, was, conducted, based, on, 'patient-relevant', outcomes, and, on, the, data]), verbo([provided]), complemento([by, the, company, in, the, dossier])]). relacion([sujeto(['The', aim, of, the, present]), verbo([report]), complemento([is, to, assess, the, added, benefit, of, aclidinium, bromide, /, formoterol, '(', hereinafter, referred, to, as, '“', aclidinium, /, 'formoterol”)', as, a, maintenance, bronchodilator, treatment, for, relief, of, symptoms, in, adult, patients, with, chronic, obstructive, pulmonary, disease, '(', 'COPD)', in, comparison, with, the, appropriate, comparator, therapy, '(', 'ACT)'])]). relacion([sujeto(['The', assessment, was, conducted, based, on, 'patient-relevant', outcomes, and, on, the, data]), verbo([provided]), complemento([by, the, company, in, the, dossier])]). relacion([sujeto(['The', aim, of, this]), verbo([report]), complemento([is, to, assess, the, added, benefit, of, nintedanib, in, combination, with, docetaxel, in, comparison, with, the, appropriate, comparator, therapy, '(', 'ACT)', in, adult, patients, with, locally, 'advanced,', metastatic, or, locally, recurrent, 'non-small', cell, lung, cancer, '(', 'NSCLC)', of, adenocarcinoma, tumour, histology, after, 'first-line', chemotherapy])]). relacion([sujeto(['The', assessment, was, conducted, based, on, 'patient-relevant', outcomes, and, on, the, evidence]), verbo([provided]), complemento([by, the, company, in, the, dossier])]). relacion([sujeto(['The', aim, of, the, present]), verbo([report]), complemento([was, to, assess, the, added, benefit, of, enzalutamide, versus, the, appropriate, comparator, therapy, '(', 'ACT)', for, treatment, of, adult, men, with, metastatic, 'castration-resistant', prostate, cancer, '(', 'mCRPC)', who, are, asymptomatic, or, mildly, symptomatic, after, failure, of, androgen, deprivation, therapy, '(', 'ADT)', in, whom, chemotherapy, is, not, yet, clinically, indicated])]). relacion([sujeto(['The', 'G-BA', specified, the, following, options, for, the, 'ACT:watchful', waiting, while]), verbo([maintaining]), complemento([ongoing, conventional, 'ADT;', 'or,', if, 'applicable,combined', maximal, androgen, blockade, with, a, 'non-steroidal', 'anti-androgen', '(', 'flutamide,', 'bicalutamide);', 'or:', abiraterone, acetate, while, maintaining, ongoing, 'ADT'])]). relacion([sujeto(['The', company, concurred, with, the, 'G-BA’s', specification, and, chose, watchful, waiting, while]), verbo([maintaining]), complemento([conventional, 'ADT', from, the, options, mentioned])]). relacion([sujeto(['The', assessment, was, conducted, based, on, 'patient-relevant', outcomes, and, on, the, evidence]), verbo([provided]), complemento([by, the, company, in, the, dossier])]). relacion([sujeto(['The', aim, of, the, present]), verbo([report]), complemento([was, the, assessment, of, the, added, benefit, of, vildagliptin, in, dual, oral, therapy, in, combination, with, a, sulfonylurea, in, comparison, with, the, appropriate, comparator, therapy, '(', 'ACT)', in, adult, patients, with, type, 2, diabetes, mellitus, with, insufficient, glycaemic, control, despite, monotherapy, with, maximal, tolerated, dose, of, a, sulfonylurea, and, for, whom, metformin, is, inappropriate, due, to, contraindications, or, intolerance])]). relacion([sujeto(['The', aim, of, this]), verbo([report]), complemento([was, to, assess, the, added, benefit, of, lurasidone, compared, with, the, appropriate, comparator, therapy, '(', 'ACT)', in, adult, patients, with, schizophrenia])]). relacion([sujeto(['The', aim, of, the, present]), verbo([report]), complemento([was, to, assess, the, added, benefit, of, simoctocog, alfa, compared, with, the, appropriate, comparator, therapy, '(', 'ACT)', in, the, treatment, and, prophylaxis, of, bleeding, in, patients, with, haemophilia, 'A', '(', congenital, factor, 'VIII', 'deficiency)'])]). relacion([sujeto(['The', assessment, was, conducted, based, on, 'patient-relevant', outcomes, and, on, the, evidence]), verbo([provided]), complemento([by, the, company])]). relacion([sujeto(['The', aim, of, this]), verbo([report]), complemento([was, to, assess, the, added, benefit, of, sucroferric, oxyhydroxide, versus, sevelamer, as, appropriate, comparator, therapy, '(', 'ACT)', for, the, control, of, serum, phosphorus, levels, in, adult, chronic, kidney, disease, '(', 'CKD)', patients, on, haemodialysis, or, peritoneal, dialysis])]). relacion([sujeto(['The', aim, of, this]), verbo([report]), complemento([was, to, assess, the, added, benefit, of, albiglutide, for, the, treatment, of, adults, with, type, 2, diabetes, mellitus, in, the, following, approved, 'subindications:', 'Monotherapy', 'When', diet, and, exercise, alone, do, not, provide, adequate, glycaemic, control, in, patients, for, whom, use, of, metformin, is, considered, inappropriate, due, to, contraindications, or, intolerance])]). relacion([sujeto(['Combination', therapy, 'In', combination, with, other, 'glucose-lowering', medicinal, products, including, basal, 'insulin,', when, 'these,', together, with, diet, and, 'exercise,', do, not]), verbo([provide]), complemento([adequate, glycaemic, control])]). relacion([sujeto(['The', aim, of, this]), verbo([report]), complemento([was, to, assess, the, added, benefit, of, idelalisib, compared, with, the, appropriate, comparator, therapy, '(', 'ACT)', specified, by, the, 'Federal', 'Joint', 'Committee', '(', 'G-BA)', for, adult, patients, with, chronic, lymphocytic, leukaemia, '(', 'CLL):', who, have, received, at, least, one, prior, 'therapy,', or, as, 'first-line', treatment, in, the, presence, of, 17, p, deletion, or, 'TP53', mutation, in, patients, unsuitable, for, 'chemo-immunotherapy'])]). relacion([sujeto(['The', following, deviations, versus, the, 'ACT', specified, by, the, 'G-BA', result, from, the, different, division, of, the]), verbo([target]), complemento([population, by, the, company, for, research, question, 1, 'c:The', company, named, chemotherapy, in, combination, with, rituximab, specified, by, the, physician, and, under, consideration, of, the, approval, status, as, 'ACT', for, patients, with, refractory, 'CLL', for, whom, antineoplastic, treatment, including, chemotherapy, is, indicated])]). relacion([sujeto(['The', aim, of, this]), verbo([report]), complemento([was, to, assess, the, added, benefit, of, nalmefene, in, comparison, with, the, appropriate, comparator, therapy, '(', 'ACT)', in, patients, with, alcohol, dependence, who, have, a, high, drinking, risk, level, '(', 'DRL),', without, physical, withdrawal, symptoms, and, who, do, not, require, immediate, detoxification])]). relacion([sujeto(['Nalmefene', should, be, initiated, only, in, patients, who, continue, to]), verbo([have]), complemento([a, high, 'DRL', 2, weeks, after, initial, assessment])]). relacion([sujeto(['The', aim, of, this]), verbo([report]), complemento([is, to, assess, the, added, benefit, of, propranolol, in, comparison, with, the, appropriate, comparator, therapy, '(', 'ACT)', in, patients, with, proliferating, infantile, haemangioma, requiring, systemic, 'therapy:', 'life-', or, 'function-threatening', 'haemangioma,', ulcerated, haemangioma, with, pain, and, /, or, lack, of, response, to, simple, wound, care, 'measures,', haemangioma, with, a, risk, of, permanent, scars, or, disfigurement])]). relacion([sujeto(['The', aim, of, the, present]), verbo([report]), complemento([is, to, assess, the, added, benefit, of, apixaban, compared, with, the, appropriate, comparator, therapy, '(', 'ACT)', for, the, treatment, of, deep, vein, thrombosis, '(', 'DVT)', and, pulmonary, embolism, '(', 'PE),', and, prevention, of, recurrent, 'DVT', and, 'PE', in, adults])]). relacion([sujeto(['The', aim, of, this]), verbo([report]), complemento([was, to, assess, the, added, benefit, of, the, fixed, combination, of, canagliflozin, and, metformin, '(', hereinafter, referred, to, as, canagliflozin, /, 'metformin)', for, the, treatment, of, adults, with, type, 2, diabetes, mellitus, in, comparison, with, the, 'ACT', in, the, following, approved, 'subindications:canagliflozin/metformin:', in, patients, with, inadequate, glycaemic, control, on, their, maximum, tolerated, dose, of, metformin, 'alone;', 'canagliflozin/metformin', in, combination, with, other, 'blood-glucose', lowering, drugs, including, 'insulin:', in, patients, with, inadequate, glycaemic, control, on, their, maximum, tolerated, dose, of, metformin, together, with, other, 'blood-glucose', lowering, drugs, including, insulin])]). relacion([sujeto(['The', aim, of, the, present, assessment, module, is, the, assessment, of, the, added, benefit, of, vedolizumab, in, comparison, with, the, appropriate, comparator, therapy, '(', 'ACT)', in, adult, patients, with, moderately, to, severely, active, ulcerative, colitis, who]), verbo([have]), complemento([had, an, inadequate, response, 'with,', lost, response, 'to,', or, are, intolerant, to, either, conventional, therapy, or, a, tumour, necrosis, factor, alpha, '(', 'TNFα)', antagonist])]). relacion([sujeto(['This', deviated, from, the, 'company’s', 'approach,', which, specified, insulin, analogues, as, comparator, therapy, without]), verbo([providing]), complemento([sufficient, justification, for, this, approach])]). relacion([sujeto(['The', aim, of, this]), verbo([report]), complemento([was, to, assess, the, added, benefit, of, dolutegravir, compared, with, the, appropriate, comparator, therapy, '(', 'ACT)', in, adults, and, adolescents, above, 12, years, of, age, infected, with, human, immunodeficiency, virus, type, 1, '(', 'HIV-1)'])]). relacion([sujeto(['The', aim, of, this]), verbo([report]), complemento([was, to, assess, the, added, benefit, of, the, fixed, combination, of, dapagliflozin, and, metformin, '(', hereinafter, referred, to, as, '“', dapagliflozin, /, 'metformin”)', for, the, treatment, of, adult, patients, with, type, 2, diabetes, mellitus, in, comparison, with, the, appropriate, comparator, therapy, '(', 'ACT)', in, the, following, approved, 'subindications:dapagliflozin', /, 'metformin:', in, patients, with, inadequate, glycaemic, control, on, their, maximum, tolerated, dose, of, metformin, 'alone;', dapagliflozin, /, metformin, in, combination, with, other, 'blood-glucose-lowering', drugs, including, 'insulin:', in, patients, with, inadequate, glycaemic, control, with, metformin, and, these, drugs])]). relacion([sujeto(['The', aim, of, the, present]), verbo([report]), complemento([is, to, assess, the, added, benefit, of, turoctocog, alfa, compared, with, the, appropriate, comparator, therapy, '(', 'ACT)', in, the, treatment, and, prophylaxis, of, bleeding, in, patients, with, haemophilia, 'A', '(', congenital, factor, 'VIII', 'deficiency)'])]). relacion([sujeto(['According', to, the, 'G-BA’s', 'specification,', all, products, containing, the, drug, octocog, alfa, would]), verbo([have]), complemento([to, be, considered])]). relacion([sujeto(['The', aim, of, the, present]), verbo([report]), complemento([was, to, assess, the, added, benefit, of, the, drug, combination, rilpivirine, /, emtricitabine, /, tenofovir, disoproxil, '(', hereinafter, referred, to, as, 'RPV', /, 'FTC', /, 'TDF)', for, the, new, therapeutic, indication, of, 'RPV', /, 'FTC', /, 'TDF', approved, in, 'November', 2013, in, comparison, with, the, appropriate, comparator, therapy, '(', 'ACT)'])]). relacion([sujeto(['The', assessment, referred, to, adults, infected, with, human, immunodeficiency, virus, type, 1, '(', 'HIV-1)', without, known, mutations]), verbo([associated]), complemento([with, resistance, to, the, 'non-nucleoside', reverse, transcriptase, inhibitor, '(', 'NNRTI)', 'class,', tenofovir, or, 'emtricitabine,', and, with, a, viral, load, '≤', 100, 0, 'HIV-1', ribonucleic, acid, '(', 'RNA)', 'copies/mL', who, have, received, previous, antiretroviral, treatment])]). relacion([sujeto(['Only', studies, with, a, minimum, duration, of, 48, weeks, '(', patients, with, previous, antiretroviral, treatment, with, several, treatment, options, after, treatment, 'failure)', or, 2, years, '(', patients, with, previous, antiretroviral, treatment, who]), verbo([respond]), complemento([to, their, current, 'treatment)', were, to, be, included])]). relacion([sujeto(['The', aim, of, this]), verbo([report]), complemento([is, to, assess, the, added, benefit, of, 'radium-223', dichloride, '(', hereinafter, referred, to, as, '“', 'radium-223”)', in, comparison, with, the, appropriate, comparator, therapy, '(', 'ACT)', in, patients, with, 'castration-resistant', prostate, 'cancer,', symptomatic, bone, metastases, and, no, known, visceral, metastases])]). relacion([sujeto(['The', aim, of, the, present]), verbo([report]), complemento([is, to, assess, the, added, benefit, of, trastuzumab, emtansine, in, patients, with, human, epidermal, growth, factor, receptor, 2, '(', 'HER2)-positive,', 'unresectable,', locally, advanced, or, metastatic, breast, cancer, who, previously, received, trastuzumab, and, a, 'taxane,', separately, or, in, combination])]). relacion([sujeto(['Patients', should]), verbo([have]), complemento([either, received, prior, treatment, for, locally, advanced, or, metastatic, 'disease,', or, developed, disease, recurrence, during, or, within, 6, months, of, completing, adjuvant, therapy])]). relacion([sujeto(['It', used, lapatinib, +, capecitabine, as, comparator, therapy, for, the, total]), verbo([target]), complemento([population])]). relacion([sujeto(['The', dossier, assessment, was, conducted, with, the, 'ACTs', specified, by, the, 'G-BA', because, the, company, did, not]), verbo([provide]), complemento([sufficient, reasons, for, deviating, from, the, 'ACTs'])]). relacion([sujeto(['The', aim, of, this, benefit, assessment, is, to, assess, the, added, benefit, of, afatinib, in, epidermal, growth, factor, receptor, '(', 'EGFR)', 'tyrosine-kinase', inhibitor, '(', 'TKI)-naive', adult, patients, with, locally, advanced, and, /, or, metastatic, 'non-small', cell, lung, cancer, '(', 'NSCLC)', with]), verbo([activating]), complemento(['EGFR', mutations])]). relacion([sujeto(['The', aim, of, this]), verbo([report]), complemento([is, to, assess, the, added, benefit, of, indacaterol, /, glycopyrronium, in, comparison, with, the, appropriate, comparator, therapy, '(', 'ACT)', in, adult, patients, with, chronic, obstructive, pulmonary, disease, '(', 'COPD)', for, maintenance, bronchodilator, treatment, to, relieve, symptoms])]). relacion([sujeto(['The', aim, of, this]), verbo([report]), complemento([is, to, assess, the, added, benefit, of, teriflunomide, in, comparison, with, the, appropriate, comparator, therapy, '(', 'ACT)', in, adult, patients, with, relapsing, remitting, multiple, sclerosis, '(', 'RRMS)'])]). relacion([sujeto(['A', search]), verbo([targeted]), complemento([at, the, comparison, with, 'Rebif', would, not, identify, studies, on, the, comparison, with, other, preparations, of, this, drug, group])]). relacion([sujeto(['The', aim, of, this]), verbo([report]), complemento([was, to, assess, the, added, benefit, of, aflibercept, '(', 'Eylea)', for, the, treatment, of, adults, with, visual, impairment, due, to, macular, oedema, secondary, to, central, retinal, vein, occlusion, '(', 'CRVO)', in, comparison, with, the, appropriate, comparator, therapy, '(', 'ACT)'])]). relacion([sujeto(['The', aim, of, this]), verbo([report]), complemento([is, to, assess, the, added, benefit, of, vemurafenib, versus, dacarbazine, as, appropriate, comparator, therapy, '(', 'ACT)', in, the, treatment, of, adult, patients, with, 'BRAF', 'V600', 'mutation-positive,', unresectable, or, metastatic, melanoma])]). relacion([sujeto(['Accordingly,', the, specific, research, question, for, the, present, assessment, was, to, what, extent, new, data, and, findings, were, presented, in, the, available, 'dossier,', and, what, influence, these]), verbo([have]), complemento([on, the, assessment, of, the, added, benefit, of, vemurafenib, from, 13, 'June', 2012])]). relacion([sujeto(['The', aim, of, this]), verbo([report]), complemento([is, to, assess, the, added, benefit, of, saxagliptin, in, comparison, with, the, appropriate, comparator, therapy, '(', 'ACT)', for, the, treatment, of, adult, patients, aged, 18, years, and, older, with, type, 2, diabetes, mellitus, for, the, therapeutic, indication, of, the, monotherapy, that, was, newly, approved, in, 'July', 2013, :, as, monotherapy, in, patients, inadequately, controlled, by, diet, and, exercise, alone, and, for, whom, metformin, is, inappropriate, due, to, contraindications, or, intolerance])]). relacion([sujeto(['The', objective, of, this]), verbo([report]), complemento([is, to, assess, the, added, benefit, of, vismodegib, in, patients, 'with:', symptomatic, metastatic, basal, cell, carcinoma, '(', 'BCC);', locally, advanced, 'BCC', inappropriate, for, surgery, or, radiotherapy])]). relacion([sujeto(['The', aim, of, this]), verbo([report]), complemento([is, to, assess, the, added, benefit, of, 'EVG', /, 'COBI', /, 'FTC', /, 'TDF', compared, with, the, appropriate, comparator, therapy, '(', 'ACT)', in, adults, infected, with, human, immunodeficiency, virus, type, 1, '(', 'HIV-1)'])]). relacion([sujeto(['The', aim, of, this]), verbo([report]), complemento([was, to, assess, the, added, benefit, of, lisdexamfetamine, as, part, of, a, comprehensive, treatment, programme, for, attention, deficit, /, hyperactivity, disorder, '(', 'ADHD)', in, children, aged, 6, years, of, age, and, over, when, response, to, previous, methylphenidate, treatment, is, considered, clinically, 'inadequate,', in, comparison, with, the, appropriate, comparator, therapy, '(', 'ACT)', atomoxetine])]). relacion([sujeto(['The', aim, of, this]), verbo([report]), complemento([is, to, assess, the, added, benefit, of, linaclotide, compared, with, the, appropriate, comparator, therapy, '(', 'ACT)', '(', medically, advised, dietary, changes, and, 'symptom-orientated', treatment, '[', 'constipation,', 'bloating,', 'cramping,', 'pain])', in, patients, with, moderate, to, severe, irritable, bowel, syndrome, with, constipation, '(', 'IBS-C)'])]). relacion([sujeto(['The', aim, of, this]), verbo([report]), complemento([is, to, assess, the, added, benefit, of, ocriplasmin, compared, with, the, appropriate, comparator, therapy, '(', 'ACT)', according, to, the, approval, for, the, following, therapeutic, 'indication:', treatment, of, vitreomacular, traction, '(', 'VMT)', in, 'adults,', including, when, associated, with, a, macular, hole, of, diameter, '≤', 400, microns])]). relacion([sujeto(['The', aim, of, this]), verbo([report]), complemento([is, to, assess, the, added, benefit, of, colestilan, for, the, treatment, of, hyperphosphataemia, in, adult, patients, with, chronic, kidney, disease, receiving, haemodialysis, or, peritoneal, dialysis, '(', hereinafter, referred, to, as, 'CKD', 5, 'D)'])]). relacion([sujeto([',', triple, combination, 'therapy)', as, an, adjunct, to, diet, and, exercise, to, improve, glycaemic, control, in, adult, patients, aged, 18, years, and, older, with, type, 2, diabetes, mellitus, when, the, maximally, tolerated, dose, of, both, metformin, and, the, sulfonylurea, does, not]), verbo([provide]), complemento([adequate, glycaemic, control])]). relacion([sujeto(['The', benefit, assessment, of, lixisenatide, was, conducted, according, to, the, approval, status, for, the, following, therapeutic, 'indication:', treatment, of, adults, with, type, 2, diabetes, mellitus, in, combination, with, oral, 'glucose-lowering', medicinal, products, 'and/or', basal, insulin, when, 'these,', together, with, diet, and, 'exercise,', do, not]), verbo([provide]), complemento([adequate, glycaemic, control])]). relacion([sujeto(['The', aim, of, this]), verbo([report]), complemento([is, to, assess, the, added, benefit, of, aflibercept, in, combination, with, a, chemotherapy, consisting, of, irinotecan, /, 5, -, fluorouracil, /, folinic, acid, '(', 'FOLFIRI)', in, comparison, with, 'FOLFIRI', as, appropriate, comparator, therapy, '(', 'ACT)', in, adult, patients, with, metastatic, colorectal, cancer, '(', 'mCRC)', that, has, progressed, during, or, after, an, 'oxaliplatin-containing', regimen])]). relacion([sujeto(['A', comparison, of, ingenol, mebutate, vehicle, and, hyaluronic, acid, gel, conducted, in, 'RCTs', would]), verbo([have]), complemento([been, 'necessary,', 'however,', to, draw, a, valid, conclusion, on, added, benefit, on, the, basis, of, the, method, chosen, by, the, company])]). relacion([sujeto(['In', the, subindication, &, 'quot;sitagliptin', plus, insulin, with, or, without, 'metformin"', '(', research, question, 'E),', the, company, defined, conventional, insulin, treatment, '(', 'CT),', intensified, conventional, insulin, treatment, '(', 'ICT)', and, insulin, dose]), verbo([increase]), complemento([as, comparator, therapies])]). relacion([sujeto(['One', aim, of, this]), verbo([report]), complemento([is, therefore, to, assess, the, added, benefit, of, apixaban, in, comparison, with, 'VKA', '(', phenprocoumon, or, 'warfarin)', in, patients, suitable, for, treatment, with, 'VKA,', in, the, indication, 'NVAF', with, one, or, more, risk, factors])]). relacion([sujeto(['Another', aim, of, this]), verbo([report]), complemento([is, to, assess, the, added, benefit, of, apixaban, in, comparison, with, 'ASA', '(', at, the, approved, dosage, of, 50, mg, to, 250, mg, 'daily)', in, patients, unsuitable, for, treatment, with, 'VKA,', in, the, indication, 'NVAF', with, one, or, more, risk, factors])]). relacion([sujeto(['Adverse', 'events:', 'bleeds:', 'combination:', major, bleeds, and, clinically, relevant, 'non-major', 'bleeds;', major, bleeds, '(', intracranial, and, extracranial, major, 'bleeds);', clinically, relevant, 'non-major', 'bleeds;', overall, rate, of, adverse, events, '(', 'AEs);', overall, rate, of, serious, adverse, events, '(', 'SAEs);', overall, rate, of, 'AEs', that]), verbo([led]), complemento([to, treatment, discontinuation])]). relacion([sujeto(['The', aim, of, this]), verbo([report]), complemento([is, to, assess, the, added, benefit, of, aflibercept, compared, with, ranibizumab, as, appropriate, comparator, therapy, '(', 'ACT)', in, adult, patients, with, wet, 'age-related', macular, degeneration, '(', 'AMD)'])]). relacion([sujeto(['These', analyses, include, an, unpublished, mathematical, simulation, by, the, manufacturer, of, ranibizumab, from, an, assessment]), verbo([report]), complemento([of, the, 'European', 'Medicines', 'Agency', '(', 'EMA),', as, well, as, extrapolations, made, by, the, company, on, the, risk, of, an, ocular, adverse, event, '(', 'AE)', of, each, intravitreal, 'injection,', and, an, analysis, called, &, 'quot;descriptive', indirect, 'comparison"'])]). relacion([sujeto(['The', appropriate, comparator, therapy, '(', 'ACT)', specified, by, the, 'Federal', 'Joint', 'Committee', '(', 'G-BA)', is, the, individual, therapy, assigned, by, the, treating, 'physician,', particularly, treatment, containing, 'bleomycin,', 'cyclophosphamide,', 'etoposide,', 'ifosfamide,', 'methotrexate,', 'mitoxantrone,', 'rituximab,', 'trofosfamide,', 'vinblastine,', 'vincristine,', or, 'vindesine,']), verbo([provided]), complemento([that, prior, therapy, allows, further, treatment, with, these, 'drugs,', and, under, consideration, of, the, respective, 'German', approval, status, and, the, approved, dosages])]). relacion([sujeto(['It']), verbo([has]), complemento([to, be, examined, for, these, studies, whether, the, study, results, are, applicable, to, a, treatment, situation, within, the, 'German', approval, 'status,', i])]). relacion([sujeto(['This']), verbo([requires]), complemento(['plausible,', 'data-based', considerations, on, why, the, therapy, chosen, in, the, study, is, an, adequate, option, for, the, 'patients,', and, is, at, least, not, inferior, to, the, 'ACT'])]). relacion([sujeto(['The', aim, of, this]), verbo([report]), complemento([is, to, assess, the, added, benefit, of, axitinib, compared, with, sorafenib, as, appropriate, comparator, therapy, '(', 'ACT)', in, patients, with, advanced, renal, cell, carcinoma, '(', 'RCC)', after, failure, of, prior, treatment, with, a, cytokine, '(', cytokine, 'population)', and, everolimus, as, 'ACT', after, failure, of, prior, treatment, with, sunitinib, '(', sunitinib, 'population)'])]). relacion([sujeto(['The', aim, of, this]), verbo([report]), complemento([is, to, assess, the, added, benefit, of, aclidinium, bromide, '(', hereinafter, abbreviated, to, '“', 'aclidinium”)', according, to, the, approval, status, for, the, following, therapeutic, 'indication:', maintenance, bronchodilator, treatment, to, relieve, symptoms, in, adult, patients, with, chronic, obstructive, pulmonary, disease, '(', 'COPD)'])]). relacion([sujeto(['Topiramate', is, appropriate, for, use, as, comparator, therapy, if, it, is, given, as, 'add-on', therapy, to, a, 'lamotrigine-containing', basic, 'therapy,']), verbo([provided]), complemento([perampanel, is, also, given, as, 'add-on', therapy, to, a, 'lamotrigine-containing', basic, therapy])]). relacion([sujeto(['The', aim, of, this]), verbo([report]), complemento([is, to, assess, the, added, benefit, of, 'linagliptin:', in, monotherapy, in, comparison, with, sulfonylureas, '(', 'glimepiride,', 'glibenclamide),', in, dual, therapy, with, metformin, in, comparison, with, sulfonylureas, '(', 'glimepiride,', 'glibenclamide)', plus, metformin, and, in, triple, therapy, with, metformin, and, a, sulfonylurea, in, comparison, with, metformin, plus, human, 'insulin;', in, each, case, as, appropriate, comparator, therapy, '(', 'ACT)', in, patients, with, type, 2, diabetes, mellitus])]). relacion([sujeto(['The', aim, of, this]), verbo([report]), complemento([is, to, assess, the, added, benefit, of, vandetanib, compared, to, best, supportive, care, '(', 'BSC)', as, appropriate, comparator, therapy, '(', 'ACT)', in, patients, with, aggressive, and, symptomatic, medullary, thyroid, carcinoma, '(', 'MTC)', with, 'unresectable,', locally, advanced, or, metastatic, disease])]). relacion([sujeto(['The', aim, of, this]), verbo([report]), complemento([is, to, assess, the, added, benefit, of, vemurafenib, versus, dacarbazine, as, appropriate, comparator, therapy, '(', 'ACT)', in, the, treatment, of, adult, patients, with, 'BRAF', 'V600', 'mutation-positive,', unresectable, or, metastatic, melanoma])]). relacion([sujeto(['The', aim, of, this]), verbo([report]), complemento([was, to, assess, the, added, benefit, of, ipilimumab, compared, to, best, supportive, care, '(', 'BSC)', as, appropriate, comparator, therapy, '(', 'ACT)', in, adult, patients, with, advanced, '(', unresectable, or, 'metastatic)', 'melanoma,', who, have, received, prior, therapy])]). relacion([sujeto(['Patients', were, also]), verbo([required]), complemento([to, receive, optimized, standard, therapy, for, 'MS', '(', including, symptomatic, treatment, with, 'spasmolytics,', if, 'necessary)'])]). relacion([sujeto(['Secondly,', the, company, gave, no, details, about, the]), verbo([required]), complemento([optimized, standard, therapy, for, 'MS'])]). relacion([sujeto(['The', aim, of, this]), verbo([report]), complemento([is, to, assess, the, added, benefit, of, rilpivirine, compared, to, efavirenz, as, appropriate, comparator, therapy, '(', 'ACT)', for, the, '“', treatment, of, human, immunodeficiency, virus, type, 1, '(', 'HIV-1)', infection, in, antiretroviral, 'treatment-naïve', adult, patients, with, a, viral, load, '≤', 100, ',', 0, 'HIV-1', 'RNA', 'copies/mL”'])]). relacion([sujeto(['The', aim, of, this]), verbo([report]), complemento([is, to, assess, the, added, benefit, of, belatacept, compared, to, ciclosporin, 'A', as, the, appropriate, comparator, therapy, '(', 'ACT)', for, prophylaxis, of, graft, rejection, in, adults, receiving, a, renal, transplant])]). relacion([sujeto([symptom, improvement, in, patients, with, moderate, to, severe, spasticity, due, to, multiple, sclerosis, '(', 'MS)', who]), verbo([have]), complemento([not, responded, adequately, to, other, 'anti-spasticity', medication, and, who, demonstrate, clinically, significant, improvement, in, spasticity, related, symptoms, during, an, initial, trial, of, 'therapy”', '(', 'Summary', of, 'Product', 'Characteristics)'])]). relacion([sujeto(['At', least, 2, previous, trials, of, therapy, were, to]), verbo([have]), complemento([taken, 'place,', in, each, of, which, different, oral, spasmolytics, -, at, least, one, of, which, had, to, be, a, product, containing, baclofen, or, tizanidine, -, were, used, in, an, optimum, way])]). relacion([sujeto(['The', aim, of, this]), verbo([report]), complemento([is, therefore, to, assess, the, added, benefit, of, 'THC/CBD', in, comparison, with, an, optimized, standard, therapy, '(', as, specified, by, the, 'G-BA)', in, patients, with, spasticity, due, to, 'MS', '(', as, described, in, the, approval, 'status)'])]). relacion([sujeto(['The', benefit, assessment, of, apixaban, was, undertaken, in, accordance, with, the, approval, status, in, the, following, therapeutic, 'indication:', '“', 'Prevention', of, venous, thromboembolic, events, '(', 'VTE)', in, adult, patients, who]), verbo([have]), complemento([undergone, elective, hip, or, knee, replacement, 'surgery”'])]). relacion([sujeto(['BSC', means, the, therapy, that]), verbo([provides]), complemento([the, patient, with, the, best, possible, individually, optimized, supportive, treatment, to, alleviate, symptoms, and, improve, the, quality, of, life])]). relacion([sujeto(['The', first, objective, of, the, present]), verbo([report]), complemento([is, therefore, to, assess, the, added, benefit, of, cabazitaxel, in, combination, with, prednisone, or, prednisolone, compared, to, 'dexamethasone,', 'prednisone,', prednisolone, or, methylprednisolone, as, well, as, 'BSC', in, patients, with, 'metastatic,', 'hormone-', refractory, prostate, 'cancer,', for, whom, further, treatment, with, docetaxel, is, no, longer, an, option])]). relacion([sujeto(['A', further, objective, of, the, present]), verbo([report]), complemento([is, therefore, to, assess, the, added, benefit, of, cabazitaxel, in, combination, with, prednisone, or, prednisolone, compared, to, docetaxel, in, combination, with, prednisone, or, prednisolone, in, patients, with, 'metastatic,', 'hormone-refractory', prostate, 'cancer,', for, whom, further, treatment, with, docetaxel, is, still, an, option])]). relacion([sujeto(['BSC', refers, to, the, therapy, that]), verbo([provides]), complemento([the, patient, with, the, best, possible, individually, optimized, supportive, treatment, to, alleviate, symptoms, and, improve, the, quality, of, life])]). relacion([sujeto(['The', first, objective, of, the, present]), verbo([report]), complemento([is, therefore, to, assess, the, added, benefit, of, abiraterone, acetate, in, combination, with, prednisone, or, prednisolone, compared, with, 'dexamethasone,', 'prednisone,', prednisolone, or, methylprednisolone, as, well, as, 'BSC', in, patients, with, mCRPC, who, are, not, eligible, for, further, treatment, with, docetaxel])]). relacion([sujeto(['A', further, objective, of, the, present]), verbo([report]), complemento([is, therefore, to, assess, the, added, benefit, of, abiraterone, acetate, in, combination, with, prednisone, or, prednisolone, compared, with, docetaxel, in, combination, with, prednisone, or, prednisolone, in, patients, with, mCRPC, who, are, not, eligible, for, further, treatment, with, docetaxel])]). relacion([sujeto(['A', failure, of, the, 'PGCs', and, 'SGPs', to, form, a, gonad, with, the, proper, architecture, not, only, affects, germ, cell, 'development,', but, can, also]), verbo([lead]), complemento([to, infertility])]). relacion([sujeto(['Therefore,', it, is, critical, to, identify, the, molecular, mechanisms, that, function, within, both, the, 'PGCs', and, 'SGPs', to]), verbo([promote]), complemento([gonad, morphogenesis])]). relacion([sujeto(['We']), verbo([have]), complemento([characterized, the, phenotypes, of, two, 'genes,', longitudinals, lacking, '(', 'lola)', and, ribbon, '(', 'rib),', that, are, required, for, the, coalescence, and, compaction, of, the, embryonic, gonad, in, 'Drosophila', melanogaster])]). relacion([sujeto([rib, and, lola, are]), verbo([expressed]), complemento([in, the, 'SGPs', of, the, developing, 'gonad,', and, genetic, interaction, analysis, suggests, these, proteins, cooperate, to, regulate, gonad, development])]). relacion([sujeto(['Both', genes, encode, proteins, with, 'DNA']), verbo([binding]), complemento([motifs, and, a, conserved, 'protein-protein', interaction, 'domain,', known, as, the, 'Broad', 'complex,', 'Tramtrack,', 'Bric-à-brac', '(', 'BTB)', domain])]). relacion([sujeto(['Through', molecular, modeling, and, 'yeast-two', hybrid, 'studies,', we, demonstrate, that, 'Rib', and, 'Lola', 'homo-', and]), verbo([heterodimerize]), complemento([via, their, 'BTB', domains])]). relacion([sujeto(['In', 'addition,', analysis, of, the, colocalization, of, 'Rib', and, 'Lola', with, marks, of, transcriptional, activation, and, repression, on, polytene, chromosomes]), verbo([reveals]), complemento([that, 'Rib', and, 'Lola', colocalize, with, both, repressive, and, activating, marks, and, with, each, other])]). relacion([sujeto(['While', previous, studies]), verbo([have]), complemento([identified, 'Rib', and, 'Lola', targets, in, other, 'tissues,', we, find, that, 'Rib', and, 'Lola', are, likely, to, function, via, different, downstream, targets, in, the, gonad])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, 'Rib', and, 'Lola', act, as, 'dual-function', transcription, factors, to, cooperatively, regulate, embryonic, gonad, morphogenesis])]). relacion([sujeto(['Radical', environmental, groups, and, their, members]), verbo([have]), complemento([a, wide, and, varied, agenda, which, often, encompasses, both, local, and, global, issues])]). relacion([sujeto(['To', obtain, these, varied, 'objectives,', radical, environmental, organizations, must, harness, their, 'networks,', which]), verbo([have]), complemento([an, important, spatial, component, that, structures, their, ability, to, 'communicate,', coordinate, and, act, on, any, given, agenda, item])]). relacion([sujeto(['Here,', we, analyze, a, network, built, from, communications, and, information]), verbo([provided]), complemento([by, the, 'semi-annual', &, 'quot;Do', or, 'Die"', '(', 'DoD)', magazine, published, in, the, 'UK', over, a, 10, year, period, in, the, late, 1990, s, and, early, 2000, s])]). relacion([sujeto(['Using', this, 'designation,', we, then, compare, the, spatial, structure, of, these, 'groups,']), verbo([finding]), complemento([that, violent, groups, are, especially, likely, to, engage, in, coordination, 'and/or', communication, if, they, are, sufficiently, 'close,', but, exhibit, a, quickly, decreasing, probability, of, interaction, over, even, a, few, kilometers])]). relacion([sujeto(['Further,', violent, and, nonviolent, groups, each]), verbo([have]), complemento([a, higher, probability, of, coordination, with, their, own, group, than, across, groups, over, even, short, distances])]). relacion([sujeto(['This']), verbo([suggests]), complemento([that, nonviolent, environmental, groups, seek, each, other, out, over, both, large, and, short, distances, for, communication, and, 'coordination,', but, violent, groups, tend, to, be, highly, localized])]). relacion([sujeto(['BACKGROUND', 'Muscle', atrophy, due, to, disuse, occurs, along, with, adverse, physiological, and, functional, 'changes,', but, bone, marrow, stromal, cells, '(', 'MSCs)', may, be, able, to]), verbo([act]), complemento([as, muscle, satellite, cells, to, restore, myofibers])]). relacion([sujeto(['Thus,', we, investigated, whether, 'MSCs', could]), verbo([enhance]), complemento([the, proliferation, of, satellite, cells, and, suppress, myonuclear, apoptosis, during, immobilization])]). relacion([sujeto(['CONCLUSIONS', 'MSCs', injected, during, hind, limb, immobilization, can]), verbo([maintain]), complemento([satellite, cell, activity, by, suppressing, myonuclear, apoptosis])]). relacion([sujeto(['Standardising', a, dual, 'x-ray', absorptiometry, '(', 'DXA)', protocol, is, thought, to]), verbo([provide]), complemento([a, reliable, measurement, of, body, composition])]). relacion([sujeto(['Eighteen', 'well-trained', male, cyclists, undertook, a, parallel, group, application, of, creatine, loading, '(', 'n=9)', '(', 20, 'g/d', for, 5, d, 'loading;', 3, 'g/d', 'maintenance)', or, placebo, '(', 'n=9)', with, crossover, application, of, glycogen, loading, '(', 12, v, 6, 'g/kg', 'BM/d', for, 48, 'h)', as, part, of, a, larger, study]), verbo([involving]), complemento([a, 'glycogen-depleting', exercise, protocol])]). relacion([sujeto(['Glycogen', 'loading,', both, with, and, without, creatine, 'loading,', resulted, in, substantial]), verbo([increases]), complemento([in, estimates, of, lean, body, mass, '(', mean, ±, 'SD;', 3.0, ±, 0.7, '%', and, 2.0, ±, 0.9, '%', ')', and, leg, lean, mass, '(', 3.1, ±, 1.8, '%', and, 2.6, ±, 1.0, '%', ')', respectively])]). relacion([sujeto(['A', substantial]), verbo([decrease]), complemento([in, leg, lean, mass, was, observed, following, the, glycogen, depleting, condition, '(', -, 1.4, ±, 1.6, '%', ')'])]). relacion([sujeto(['Total', body, water, showed, substantial]), verbo([increases]), complemento([following, glycogen, loading, '(', 2.3, ±, 2.3, '%', ')', ',', creatine, loading, '(', 1.4, ±, 1.9, '%', ')', and, the, combined, treatment, '(', 2.3, ±, 1.1, '%', ')'])]). relacion([sujeto(['Corin', is, a, transmembrane, protease, that]), verbo([activates]), complemento([atrial, natriuretic, peptide, '(', 'ANP),', an, important, hormone, in, regulating, 'salt-water', balance, and, blood, pressure])]). relacion([sujeto(['Proprotein', convertase, 'subtilisin/kexin-6']), verbo([has]), complemento([been, identified, as, a, primary, enzyme, that, converts, zymogen, corin, to, an, active, protease])]). relacion([sujeto(['Genetic', variants, that, impair, corin, intracellular, 'trafficking,', cell, surface, 'expression,', and, zymogen, activation]), verbo([have]), complemento([been, found, in, patients, with, 'hypertension,', cardiac, 'hypertrophy,', and, 'pre-eclampsia'])]). relacion([sujeto(['Reduced', corin, expression]), verbo([has]), complemento([been, detected, in, animal, models, of, cardiomyopathies, and, in, human, failing, hearts])]). relacion([sujeto(['Low', levels, of, circulating, soluble, corin]), verbo([have]), complemento([been, reported, in, patients, with, heart, disease, and, stroke])]). relacion([sujeto(['Corin,', 'ANP', and, natriuretic, peptide, 'receptor-A', 'mRNAs,', and, proteins]), verbo([have]), complemento([been, colocalized, in, human, renal, 'segments,', suggesting, a, 'corin-ANP', autocrine, function, in, the, kidney])]). relacion([sujeto(['The', latest, findings, indicate, that, 'corin-mediated', 'ANP', production, may]), verbo([act]), complemento([in, a, 'tissue-specific', manner, to, regulate, cardiovascular, and, renal, function])]). relacion([sujeto(['Long', 'non-coding', 'RNAs', '(', 'lncRNAs)']), verbo([have]), complemento([been, reported, to, play, pivotal, roles, in, multiple, tumors, and, can, act, as, tumor, biomarkers])]). relacion([sujeto(['DGCR5', was]), verbo([found]), complemento(['down-regulated', in, 'HCC', tissues, '(', 'P<0'])]). relacion([sujeto(['Our', results]), verbo([suggest]), complemento([that, 'DGCR5', may, be, a, participator, in, 'HCC', and, can, serve, as, potential, biomarker, for, the, diagnosis, and, prognosis, in, 'HCC'])]). relacion([sujeto(['Improved', micropollutant, '(', 'MP)', biotransformation, during, biological, wastewater, treatment]), verbo([has]), complemento([been, associated, with, high, ammonia, oxidation, 'activities,', suggesting, 'co-metabolic', biotransformation, by, ammonia, oxidizing, bacteria, as, an, underlying, mechanism])]). relacion([sujeto(['The', goal, of, this, study, was, to, clarify, the, contribution, of, ammonia, oxidizing, bacteria, to]), verbo([increased]), complemento(['MP', degradation, in, nitrifying, activated, sludge, '(', 'NAS)', communities, using, a, series, of, inhibition, experiments])]). relacion([sujeto(['To', this, 'end,', we, treated, a, 'NAS', community, with, two, different, ammonia, oxidation, 'inhibitors,', namely, octyne, '(', 'OCT),', a, mechanistic, inhibitor, that, covalently]), verbo([binds]), complemento([to, ammonia, 'monooxygenases,', and, allylthiourea, '(', 'ATU),', a, copper, chelator, that, depletes, copper, ions, from, the, active, center, of, ammonia, monooxygenases])]). relacion([sujeto(['Of', 'these,', 31, compounds, were, significantly]), verbo([inhibited]), complemento([by, either, 'ATU', 'and/or', 'OCT'])]). relacion([sujeto(['This', was, particularly, the, case, for, almost, all, thioether, and, phenylurea, compounds, 'tested,']), verbo([suggesting]), complemento([that, in, nitrifying, activated, sludge, 'communities,', 'ATU', does, not, exclusively, act, as, an, inhibitor, of, bacterial, ammonia, oxidation])]). relacion([sujeto(['Rather,', 'ATU', also]), verbo([inhibited]), complemento([enzymes, contributing, to, 'MP', biotransformation, but, not, to, bulk, ammonia, oxidation])]). relacion([sujeto(['Thus,', inhibition, studies, with, 'ATU', tend, to, overestimate, the, contribution, of, 'ammonia-oxidizing', bacteria, to, 'MP', biotransformation, in, nitrifying]), verbo([activated]), complemento([sludge, communities])]). relacion([sujeto(['Biolog', tests, revealed, only, minor, effects, of, 'ATU', on, the, heterotrophic, respiration, of, common, organic, substrates, by, the, sludge, 'community,']), verbo([suggesting]), complemento([that, 'ATU', did, not, affect, enzymes, that, were, essential, in, energy, conservation, and, central, metabolism, of, heterotrophs])]). relacion([sujeto(['By', comparing, 'ATU-', and, 'OCT-treated', 'samples,', as, well, as, before, and, after, ammonia, oxidation, was, recovered, in, 'OCT-treated', 'samples,', we, were, able, to, demonstrate, that, 'ammonia-oxidizing', bacteria, were, highly]), verbo([involved]), complemento([in, the, biotransformation, of, four, 'compounds:', 'asulam,', 'clomazone,', monuron, and, trimethoprim])]). relacion([sujeto(['The', capability, of, clostridia, spores, to]), verbo([act]), complemento([as, pathogen, indicators, in, sewage, sludge, treatment, was, investigated])]). relacion([sujeto([coli, levels, were, monitored, during, waste]), verbo([activated]), complemento([sludge, 'pre-treatments', '(', alkali, and, 'ultrasound)', and, its, subsequent, mesophilic, anaerobic, digestion])]). relacion([sujeto([coli, was]), verbo([maintained]), complemento([or, reduced, depending, on, treatment, type, and, intensity])]). relacion([sujeto(['However,', alkali, 'pre-treatment', '(', 35.3, 'gNaOH/kgTS)', by, itself, and, alkali, '(', 157, 'gNaOH/kgTS)', and, ultrasound, '(', 27, ',', 0, 'kJ/kgTS)', 'pre-treatments', followed, by, anaerobic, digestion]), verbo([provoked]), complemento([reproducible, clostridia, increases])]). relacion([sujeto(['Having', rejected, the, hypotheses, of, sporulation, and, floc, 'dissipation,', the, most, plausible, explanation, for, these, clostridia]), verbo([increases]), complemento([is, 're-growth'])]). relacion([sujeto(['These', results, question, the, suitability, of, clostridia, spores, as, indicators, of, sludge, treatment, and, other, biological, treatments, where, clostridia, may]), verbo([have]), complemento([a, role])]). relacion([sujeto(['Worldwide,', the, sustainability, of, public, health, systems, is, challenged, by, the]), verbo([increasing]), complemento([number, and, cost, of, personalized, therapies])]). relacion([sujeto(['Quality', biological, samples, stored, in, biobanks, are, essential, for, the, provision, of, appropriate, health, services, and, also]), verbo([act]), complemento([as, a, reservoir, for, the, development, of, precision, medicine, and, biotechnological, innovation])]). relacion([sujeto(['Abnormal', redox, homeostasis, and, oxidative, stress]), verbo([have]), complemento([been, proposed, to, play, a, role, in, the, etiology, of, several, neuropsychiatric, spectrum, disorders])]). relacion([sujeto(['Emerging', interest]), verbo([has]), complemento([recently, focused, on, markers, of, oxidative, stress, and, neuroinflammation, in, schizophrenic, spectrum, 'disorders,', at, least, in, particular, subgroups, of, patients])]). relacion([sujeto(['Altered', expression, of, genes, related, to, oxidative, 'stress,', oxidative, damage, to, 'DNA,', protein, and, 'lipids,', as, well, as, reduced, glutathione, levels, in, central, and, peripheral, tissues, could]), verbo([act]), complemento(['synergistically,', and, contribute, to, the, course, of, the, disease])]). relacion([sujeto(['We', address, modulation, of, endogenous, cellular, defense, mechanisms, as, a, potentially, innovative, approach, to, therapeutics, for, 'schizophrenia,', and, other, neuropsychiatric, conditions, that, are]), verbo([associated]), complemento([with, neuroinflammation])]). relacion([sujeto(['Finally', we, introduce, the, hormetic, dose, response, concept, as, relevant, and, important, to, 'neuroprotection,', and, review, hormetic, mechanisms, as, possible, approaches, to, manipulation, of, neuroinflammatory]), verbo([targets]), complemento([that, may, be, viable, for, treating, schizophrenia, spectrum, disorders])]). relacion([sujeto(['The', importance, of, 'Glucagon', like, peptide, 1, '(', 'GLP-1)', for, metabolic, control, and, insulin]), verbo([release]), complemento([sparked, the, evolution, of, genes, mimicking, 'GLP-1', action, in, venomous, species, '(', e])]). relacion([sujeto(['We', discovered, that, platypus, and, echidna]), verbo([express]), complemento([a, single, 'GLP-1', peptide, in, both, intestine, and, venom])]). relacion([sujeto(['Specific', changes, in, 'GLP-1', of, monotreme, mammals, result, in, resistance, to, 'DPP-4', cleavage, which, is, also, observed, in, the, 'GLP-1', like, 'Exendin-4']), verbo([expressed]), complemento([in, 'Heloderma', venom])]). relacion([sujeto(['We', also, show, that, monotreme, 'GLP-1']), verbo([stimulates]), complemento([insulin, release, in, cultured, rodent, 'islets,', but, surprisingly, shows, low, receptor, affinity, and, bias, toward, 'Erk', signaling])]). relacion([sujeto(['This']), verbo([provides]), complemento([novel, insight, into, the, remarkably, different, metabolic, control, mechanism, and, venom, function, in, monotremes, and, an, unique, example, of, how, different, selective, pressures, act, upon, a, single, gene, in, the, absence, of, gene, duplication])]). relacion([sujeto([restrictus, strain, 'PER-K23,', strains, 'CF', and, 'DCA']), verbo([require]), complemento(['arginine,', histidine, and, threonine, for, 'growth,', although, the, corresponding, biosynthesis, pathways, are, predicted, to, be, functional])]). relacion([sujeto(['Consistent', with, 'annotation,', strain, 'CF', possesses, a, functional, corrinoid, biosynthesis, 'pathway,', demonstrated, by]), verbo([increasing]), complemento([corrinoid, content, during, growth, and, guided, cobalamin, biosynthesis, in, 'corrinoid-free', medium])]). relacion([sujeto(['Heme', detection, in, strain, 'CF', cell, extracts]), verbo([suggests]), complemento([the, '\'', 'archaeal\'', heme, biosynthesis, pathway, also, functions, in, anaerobic, 'Firmicutes'])]). relacion([sujeto(['This', strategy]), verbo([leads]), complemento([to, an, upregulation, of, several, 'exercise-responsive', signaling, 'proteins,', but, the, chronic, effect, on, performance, has, received, less, attention])]). relacion([sujeto(['The', improvement, was]), verbo([associated]), complemento([with, a, change, in, pacing, strategy, with, higher, power, output, during, the, second, part, of, the, test])]). relacion([sujeto(['Lipid', peroxidation, 'products,', such, as, 7, -, ketocholesterol, '(', 7, 'KC),', may, be]), verbo([increased]), complemento([in, the, body, fluids, and, tissues, of, patients, with, neurodegenerative, diseases, and, trigger, microglial, dysfunction, involved, in, neurodegeneration])]). relacion([sujeto(['We', determined, the, impact, of, 7, 'KC', on, murine, microglial, 'BV-2', 'cells,', especially, its, ability, to]), verbo([trigger]), complemento([mitochondrial, and, peroxisomal, 'dysfunction,', and, evaluated, the, protective, effects, of, 'α-', and, 'γ-tocopherol,', 'Trolox,', and, oleic, acid, '(', 'OA)'])]). relacion([sujeto(['However,', only, 'α-tocopherol,', 'γ-tocopherol', and, 'OA', were, able, to, impair, 7, 'KC-induced']), verbo([loss]), complemento([of, mitochondrial, transmembrane, 'potential,', which, is, associated, with, increased, permeability, to, propidium, 'iodide,', an, indicator, of, cell, death])]). relacion([sujeto(['In', 'addition,', 'α-and', 'γ-tocopherol,', and, 'OA', were, able, to]), verbo([prevent]), complemento([the, decrease, in, 'Abcd3', protein, 'levels,', which, allows, the, measurement, of, peroxisomal, 'mass,', and, in, mRNA, levels, of, 'Abcd1', and, 'Abcd2,', which, encode, for, two, transporters, involved, in, peroxisomal, 'β-oxidation'])]). relacion([sujeto(['Thus,', 7, 'KC-induced', side, effects, are]), verbo([associated]), complemento([with, mitochondrial, and, peroxisomal, dysfunction, which, can, be, inversed, by, natural, 'compounds,', thus, supporting, the, hypothesis, that, the, composition, of, the, diet, can, act, on, the, function, of, organelles, involved, in, neurodegenerative, diseases])]). relacion([sujeto(['A', growing, body, of, evidence]), verbo([has]), complemento([demonstrated, that, multiple, sources, of, salience, tune, attentional, sets, toward, aspects, of, the, 'environment,', including, affectively, and, motivationally, significant, categories, of, stimuli, such, as, angry, faces, and, 'reward-associated', target, locations])]). relacion([sujeto(['Recent', evidence, further, indicates, that, objects, that]), verbo([have]), complemento([gained, personal, significance, through, ownership, can, elicit, similar, attentional, prioritization])]). relacion([sujeto(['To', begin, to, address, this, 'gap,', we, propose, the, 'Self', as, 'Ownership', in, 'Attentional', 'Prioritization', '(', 'SOAP)', framework, to, explain, how, ownership]), verbo([increases]), complemento([salience, through, attention, to, external, representations, of, 'self-identity', '(', i])]). relacion([sujeto([',', self, as, 'object)', and, attention, to, contextually]), verbo([mediated]), complemento([permission, to, act, '(', i])]). relacion([sujeto(['Additionally,', these, cytokines, may]), verbo([act]), complemento([as, autocrine, growth, factors, in, pancreatic, cancer, cells])]). relacion([sujeto(['We', hypothesize, that, 'IL-4,', 'IL-13,', and, their, corresponding, receptors, are]), verbo([involved]), complemento([in, mechanism, of, cancer, cachexia])]). relacion([sujeto(['We', speculate, that, suppression, of, 'IL-4', is]), verbo([involved]), complemento([in, cancer, 'cachexia,', although, the, exact, mechanisms, have, to, be, further, elucidated])]). relacion([sujeto(['Taken', 'altogether,', our, results, indicate, that, ageing, in, sedentary, men, is]), verbo([associated]), complemento([with, '(', 'i)', complex, changes, in, muscle, phenotype, preferentially, affecting, type, 'IIa', 'fibres;', '(', 'ii)', a, decline, in, mitochondrial, content, affecting, all, fibre, 'types;', and, '(', 'iii)', an, increase, in, lipid, content, in, type, 'I', fibres])]). relacion([sujeto(['Police']), verbo([have]), complemento([historically, been, responsible, for, transporting, people, during, a, mental, health, crisis, in, 'Australia'])]). relacion([sujeto(['Double-side', 'Pt-decoration', of, the, tube, membranes]), verbo([leads]), complemento([to, higher, 'H2', generation, rates, '(', independent, of, tube, and, light, irradiation, 'configuration)', compared, to, membranes, decorated, at, only, one, side, with, similar, overall, 'Pt', amounts])]). relacion([sujeto(['The', results]), verbo([suggest]), complemento([that, this, effect, is, not, ascribed, to, the, overall, amount, of, 'Pt', cocatalyst, as, such, but, rather, to, its, distribution, at, both, tube, extremities])]). relacion([sujeto(['This']), verbo([leads]), complemento([to, optimized, light, absorption, and, electron, 'diffusion/transfer', 'dynamics:', the, central, part, of, the, membranes, act, as, light, harvesting, zone, and, electrons, therein, generated, can, diffuse, towards, the, 'Pt/TiO2', active, zones, '(', tube, 'extremities)', where, they, can, react, with, the, environment, and, generate, 'H2', gas])]). relacion([sujeto(['These', findings, indicate, that, 'ActIV', is, a, bifunctional, 'CYC-TE', and]), verbo([provide]), complemento(['clear-cut', evidence, for, the, release, timing, of, the, intermediate, from, the, 'ACP', anchor])]). relacion([sujeto(['In', 'addition,', electron, doping, can]), verbo([act]), complemento([as, another, means, to, influence, 'MoS2-substrate', interactions, and, enable, further, phase, engineering, of, 'MoS2'])]). relacion([sujeto(['However,', it]), verbo([has]), complemento([recently, been, claimed, that, lonsdaleite, does, not, exist, as, a, 'well-defined', material, but, is, instead, defective, cubic, diamond, formed, under, high, pressure, and, high, temperature, conditions])]). relacion([sujeto(['Here', we]), verbo([report]), complemento([the, synthesis, of, almost, pure, lonsdaleite, in, a, diamond, anvil, cell, at, 100, 'GPa', and, 400, °, 'C'])]). relacion([sujeto(['This', strain]), verbo([induced]), complemento([transformation, of, the, graphitic, planes, of, the, precursor, to, hexagonal, diamond, is, supported, by, first, principles, calculations, of, transformation, pathways, and, explains, why, the, new, phase, is, found, in, an, annular, region])]). relacion([sujeto(['Our', findings, establish, that, high, purity, lonsdaleite, is, readily, formed, under, strain, and, hence, does, not]), verbo([require]), complemento([meteoritic, impacts])]). relacion([sujeto(['The', goal, of, this, project, was, to, characterize, the, molecular, and, cellular, roles, of, various, gene]), verbo([targets]), complemento([regulated, by, 8, miRNAs, in, differentiating, macrophages])]). relacion([sujeto(['Among', a, number, of, miRNAs, that, are]), verbo([found]), complemento([to, be, expressed, in, avian, 'macrophages,', we, focused, on, eight, specific, miRNAs, '(', 'miR-1618,', 'miR-1586,', 'miR-1633,', 'miR-1627,', 'miR-1646,', 'miR-1649,', 'miR-1610,', 'miR-1647)', associated, with, macrophage, activation, through, 'Wnt', 'signaling,', 'ubiquitination,', 'PPAR', mediated, macrophage, 'function,', vesicle, mediated, cytokine, 'trafficking,', and, 'WD40', domain, proteins, in, macrophage, differentiation])]). relacion([sujeto(['The', results, of, our, analysis, identified, a, global, theme, for, macrophage, 'function:', 'Differentiation', and, activation, of, macrophages]), verbo([requires]), complemento([a, comprehensive, redistribution, of, the, 'cell\'s', protein, repertoire])]). relacion([sujeto(['This', redistribution]), verbo([involves]), complemento([two, 'processes:', 1, ')', the, degradation, and, recycling, of, unneeded, cytoplasmic, and, membrane, components, and, 2, ')', the, mobilization, of, newly, synthesized, cellular, components, via, vesicular, trafficking])]). relacion([sujeto(['Ultimately,', this]), verbo([leads]), complemento([to, a, change, in, the, membrane, surface, expression, profile, of, the, cell, as, well, as, to, a, change, in, proteins, regulating, phagosomal, and, lysosomal, compartments, facilitating, increased, efficiency, of, phagocytic, activity])]). relacion([sujeto(['Once', a, monocyte, arrives, to, a, site, of, 'infection,', local, signals]), verbo([induce]), complemento([a, redistribution, of, resources, into, a, 'pro-phagocytic', phenotype])]). relacion([sujeto(['This', may]), verbo([involve]), complemento([upregulating, pathogen, pattern, recognizing, receptors, and, increasing, the, efficiency, of, lysosomal, 'biogenesis,', while, simultaneously, recycling, components, involved, in, circulatory, migration, and, leukocyte, extravasation])]). relacion([sujeto(['In', 'parallel,', 'Wnt', and, 'NF-κB', signal, transduction]), verbo([induces]), complemento([expression, of, cytokine, signals, that, act, in, an, autocrine, and, paracrine, 'manner,', driving, this, process, of, 'self-differentiation', as, well, as, inducing, differentiation, of, nearby, monocytes, into, macrophages])]). relacion([sujeto(['In', this, study, we, focused, on, two, main, 'phases:', miRNA]), verbo([associated]), complemento([with, genes, modulating, monocyte, to, macrophage, differentiation, and, miRNA, mediating, macrophage, 'function/response', to, infection, or, inflammation])]). relacion([sujeto(['Among', the, hundreds, of, genes, that, these, miRNA, 'target,', our, analysis, identified, a, set, of, them, that]), verbo([provide]), complemento([insight, into, avian, macrophage, biology])]). relacion([sujeto(['Glioblastoma', multiforme, '(', 'GBM)', is, the, most, common, and, fatal, intracranial, cancer, in, humans, and, exhibits, intense, and, aberrant, angiogenesis, that, sustains, its, malignancy, and]), verbo([involves]), complemento([several, angiogenic, signals])]). relacion([sujeto(['Different', cells, appear, to]), verbo([act]), complemento([as, triggers, of, the, aberrant, 'angiogenesis,', 'and,', among, 'them,', platelets, act, as, key, participants])]). relacion([sujeto(['In', order, to]), verbo([provide]), complemento([further, insights, into, the, platelet, features, and, angiogenic, role, in, 'GBM,', this, study, investigated, the, effects, of, platelet, releasate, on, 'GBM-derived', endothelial, cells, '(', 'GECs)', and, the, levels, of, 'VEGF', and, 'endostatin,', as, 'pro-', and, 'anti-angiogenic', components, of, platelet, releasate, from, 'GBM', patients])]). relacion([sujeto(['We', demonstrate, for, the, first, time, 'that:', 1, ')', platelet, releasate, exerts, powerful, 'pro-angiogenic', effect, on, 'GECs,']), verbo([suggesting]), complemento([it, might, exert, a, role, in, the, aberrant, angiogenesis, of, 'GBM;', 2, ')', 'ADP', and, thrombin, stimulation, leads, to, significantly, higher, level, of, 'VEGF,', but, not, of, 'endostatin,', in, the, releasate, of, platelets, from, 'GBM', patients, than, those, from, healthy, 'subjects;', and, 3, ')', the, intraplatelet, concentrations, of, 'VEGF', were, significantly, elevated, in, 'GBM', patients, as, compared, to, controls])]). relacion([sujeto(['Moreover,', we]), verbo([found]), complemento([a, direct, correlation, between, 'platelet-released', 'VEGF', and, overall, survival, in, our, patient, cohort])]). relacion([sujeto(['The', treatment, of, 'B', cell, malignancies, by, adoptive, cell, transfer, '(', 'ACT)', of, 'anti-CD19', chimeric, antigen, receptor, 'T', cells, '(', 'CD19', 'CAR-T)']), verbo([has]), complemento([proven, to, be, a, highly, successful, therapeutic, modality, in, several, clinical, 'trials<sup>1-6</sup>'])]). relacion([sujeto(['In', this, 'study,', we]), verbo([report]), complemento([a, procedure, for, generating, 'CD19', 'CAR-T', cells, in, 6, 'days,', using, a, predominantly, closed, manufacturing, process, and, 'defined,', 'serum-free', medium])]). relacion([sujeto(['Electronic', health, records, '(', 'EHRs)']), verbo([have]), complemento([become, a, vital, source, of, patient, outcome, data, but, the, widespread, prevalence, of, missing, data, presents, a, major, challenge])]). relacion([sujeto(['Different']), verbo([causes]), complemento([of, missing, data, in, the, 'EHR', data, may, introduce, unintentional, bias])]). relacion([sujeto(['With', continued, rapid, growth, in, the, number, and, quality, of, fully, sequenced, and, accurately, annotated, bacterial, 'genomes,', we]), verbo([have]), complemento([unprecedented, opportunities, to, understand, metabolic, diversity])]). relacion([sujeto(['The', presence, or, absence, of, these, variants]), verbo([act]), complemento([as, a, metabolic, signature, for, each, of, the, 'bacteria,', which, can, then, be, used, to, understand, similarities, and, differences, between, and, across, bacterial, groups])]). relacion([sujeto(['The', positive, results, of, this, manual, curation, effort, and, novel, method, development]), verbo([suggest]), complemento([that, future, work, is, needed, to, further, expand, the, set, of, bacteria, to, which, this, approach, is, applied, and, use, the, resulting, tree, to, test, broad, questions, about, metabolic, diversity, and, complexity, across, the, bacterial, tree, of, life])]). relacion([sujeto(['Several', methods]), verbo([have]), complemento([been, developed, to, identify, suitable, models, of, evolution, for, phylogenetic, analysis, of, alignments, of, nucleotide, or, amino, acid, sequences, and, some, of, these, methods, are, now, firmly, embedded, in, the, phylogenetic, protocol])]). relacion([sujeto(['If', an, agent, did, not, know, and, could, not]), verbo([have]), complemento([known, that, her, action, would, realize, some, bad, 'outcome,', then, it, is, plausible, to, maintain, that, she, is, not, to, blame, for, realizing, that, 'outcome,', even, when, the, act, that, leads, to, this, outcome, is, wrong])]). relacion([sujeto(['This', general, thought, can, be, brought, to, bear, in, the, context, of, climate, change, insofar, as, we, think, '(', 'a)', that, the, actions, of, individual, agents, play, some, role, in, realizing, climate, harms, and, '(', 'b)', that, these, actions, are, apt]), verbo([targets]), complemento([for, being, considered, right, or, wrong])]). relacion([sujeto(['We', used, conventional, content, analysis, to, conduct, a, 'cross-case', comparison, to, identify, common, features, of, rural, counties, that, successfully, implemented, and, sustained, their]), verbo([target]), complemento(['evidence-based', health, promotion, program])]). relacion([sujeto(['The', proof, that, several, genetic, loci, are, responsible, for, rare, 'Mendelian', forms]), verbo([has]), complemento([represented, a, revolutionary, 'breakthrough,', enabling, to, reveal, molecular, mechanisms, underlying, this, debilitating, still, incurable, condition])]). relacion([sujeto(['While', single, nucleotide, polymorphisms, '(', 'SNPs)', and, small, indels, constitute, the, most, commonly, investigated, 'DNA', variations, accounting, for, only, a, limited, number, of, 'PD', 'cases,', larger, genomic, molecular, rearrangements]), verbo([have]), complemento([emerged, as, significant, 'PD-causing', 'mutations,', including, submicroscopic, 'Copy', 'Number', 'Variations', '(', 'CNVs)'])]). relacion([sujeto(['CNVs', constitute, a, prevalent, source, of, genomic, variations, and, substantially]), verbo([participate]), complemento([in, each, 'individual\'s', genomic, makeup, and, phenotypic, outcome])]). relacion([sujeto(['However,', the, majority, of, genetic, studies]), verbo([have]), complemento([focused, their, attention, on, single, 'candidate-gene', mutations, or, on, common, variants, reaching, a, significant, statistical, level, of, acceptance])]). relacion([sujeto(['We', will, analyze, the, most, frequent, copy, number, changes, in, familiar, 'PD', genes, and]), verbo([provide]), complemento([a, &, 'quot;systems', 'biology"', overview, of, rare, individual, rearrangements, that, could, functionally, act, on, commonly, deregulated, molecular, pathways])]). relacion([sujeto(['Assessing', the, global, 'genome-wide', burden, of, 'CNVs', in, 'PD', patients, may]), verbo([reveal]), complemento([new, 'disease-related', molecular, 'mechanisms,', and, open, the, window, to, a, new, possible, genetic, scenario, in, the, unsolved, 'PD', puzzle])]). relacion([sujeto(['In', compliance, with, the, present, 'Asylum', 'Seekers', 'Benefits', 'Act,', the, national, healthcare, system, can, be, expected, to]), verbo([have]), complemento([1.5, &, 'nbsp;million', new, members, by, early, 2017])]). relacion([sujeto(['The', circumstances, of, the, flight, combined, with, the, foreign, linguistic, and, 'socio-cultural', background]), verbo([increase]), complemento([the, severity, of, the, cases, and, the, difficulties, of, treatment])]). relacion([sujeto(['No', procedures, or, guidelines, for, treatment]), verbo([have]), complemento([yet, been, established, to, ensure, 'a standardized,', 'cost-efficient', and, therapeutically, effective, treatment, of, patients, with, this, background])]). relacion([sujeto(['This', approach, is, based, on, national, and, international, treatment, guidelines, and, aims, to]), verbo([provide]), complemento(['target-group', 'specific,', culturally, sensitive, methods, of, diagnosis, and, treatment])]). relacion([sujeto(['The', most, trusted, hypothesis, to, explain, how, 'α2-adrenergic', agonists, may, preserve, pulmonary, functions, in, critically, ill, patients, is, that, they, directly]), verbo([act]), complemento([on, macrophages, by, interfering, with, an, 'autocrine/paracrine', adrenergic, system, that, controls, cytokine, release, through, locally, synthetized, noradrenaline, and, 'α1-', and, 'α2-adrenoreceptors'])]). relacion([sujeto(['To', evaluate, whether, α2, adrenoreceptors, controlled, cytokine]), verbo([release]), complemento([from, 'HMLs,', we, measured, 'IL-6,', 'IL-8', and, 'TNF-α', concentrations, in, the, culture, medium, in, basal, conditions, and, after, preincubation, with, several, 'α2-adrenergic', agonists, or, antagonists])]). relacion([sujeto(['Neither', the, pretreatment, with, the, 'α2-adrenergic', agonists, 'clonidine,', medetomidine, or, dexdemetomidine, or, with, the, 'α2-adrenergic', antagonist, yohimbine]), verbo([caused]), complemento([significant, changes, in, the, response, of, any, of, these, cytokines, to, 'LPS'])]). relacion([sujeto(['These', results, show, 'that,', different, from, what]), verbo([reported]), complemento([in, 'rodents,', clonidine, and, dexdemetomidine, do, not, directly, suppress, cytokine, release, from, human, pulmonary, macrophages])]). relacion([sujeto(['This']), verbo([suggests]), complemento([that, alternative, mechanisms, such, as, effects, on, immune, cells, activation, or, the, modulation, of, autonomic, neurotransmission, could, be, responsible, for, the, beneficial, effects, of, these, drugs, on, lung, function, in, critical, patients])]). relacion([sujeto(['Melanoma']), verbo([has]), complemento([emerged, as, a, paradigm, of, a, highly, aggressive, and, plastic, 'cancer,', capable, to, 'co-opt', the, tumor, stroma, in, order, to, adapt, to, the, hostile, 'microenvironment,', suppress, immunosurveillance, 'mechanisms,', and, disseminate])]). relacion([sujeto(['Research', over, the, past, decade]), verbo([has]), complemento([indicated, that, alterations, in, key, nodes, of, these, proteostasis, pathways, act, in, conjunction, with, crucial, oncogenic, drivers, to, increase, intrinsic, adaptations, of, melanoma, cells, against, proteotoxic, 'stress,', modulate, the, high, metabolic, demand, of, these, cancer, cells, and, the, interface, with, other, stromal, 'cells,', through, the, heightened, release, of, soluble, factors, or, exosomes])]). relacion([sujeto(['Here,', we, overview, and, discuss, how, key, proteostasis, pathways, and, vesicular, trafficking, mechanisms, are, turned, into, vital, conduits, of, melanoma, 'progression,', by, supporting, cancer, 'cell\'s', adaptation, to, the, 'microenvironment,', limiting, or]), verbo([modulating]), complemento([the, ability, to, respond, to, therapy, and, fueling, melanoma, dissemination])]). relacion([sujeto(['A', pressure, sore, wound, is, often, extensive, or, complicated, by, local, infection]), verbo([involving]), complemento([adjacent, soft, tissue, and, bone])]). relacion([sujeto(['The', large, soft, tissue, defect, with, significant, depth, was, reconstructed, with, a, free, latissimus, dorsi, musculocutaneous, 'flap,', which, was, expected, to]), verbo([act]), complemento([as, a, local, barrier, from, vertical, infection, and, provide, tensionless, skin, coverage, upon, hip, flexion])]). relacion([sujeto(['This', study, investigated, the, occurrence, and, types, of, adverse, effects]), verbo([associated]), complemento([with, exposure, to, fragranced, products, in, 'Australia,', and, opportunities, for, prevention])]). relacion([sujeto(['Overall,', 33, '%', of, 'Australians']), verbo([report]), complemento([health, 'problems,', such, as, migraine, headaches, and, asthma, 'attacks,', when, exposed, to, fragranced, products])]). relacion([sujeto(['Additionally,', 7.7, '%', of, 'Australians']), verbo([have]), complemento([lost, workdays, or, a, job, due, to, illness, from, fragranced, product, exposure, in, the, 'workplace,', 16.4, '%', reported, health, problems, when, exposed, to, air, fresheners, or, 'deodorizers,', 15.3, '%', from, being, in, a, room, after, it, was, cleaned, with, scented, 'products,', and, 16.7, '%', would, enter, but, then, leave, a, business, as, quickly, as, possible, due, to, fragranced, products])]). relacion([sujeto(['This', is, the, first, study, in, 'Australia', to, assess, the, extent, of, adverse, effects]), verbo([associated]), complemento([with, exposure, to, common, fragranced, products])]). relacion([sujeto(['It']), verbo([provides]), complemento([compelling, evidence, for, the, importance, and, value, of, reducing, fragranced, product, exposure, in, order, to, reduce, and, prevent, adverse, health, effects, and, costs])]). relacion([sujeto(['The', present, study]), verbo([found]), complemento(['that,', similarly, to, 5, -, 'fluorouracil,', low, concentrations, '(', 1, -, 10, 'µM)', of, 9, -, aminoacridine, '(', 9, -, 'AAA)', inhibited, the, growth, of, the, two, rat, prostate, cancer, 'AT-2', and, 'Mat-LyLu', cell, lines, and, the, human, melanoma, 'A375', cell, line])]). relacion([sujeto(['The', differences, between, the, cellular, responses, of, the, 'AT-2', and, 'Mat-LyLu', cell, 'lines,', which, differ, in, 'malignancy,', were]), verbo([found]), complemento([to, be, relatively, small, compared, with, the, differences, between, normal, 'HSFs', and, the, cancer, cell, lines])]). relacion([sujeto(['Visible', effects, on, the, cell, growth, and, survival, of, tumor, cell, lines, were, observed, after, 24, -, 48, h, of, treatment, with, 9, -, 'AAA,', and]), verbo([increased]), complemento([over, time])]). relacion([sujeto(['The', inhibition, of, cancer, cell, growth, was]), verbo([found]), complemento([to, be, due, to, the, gradually, increasing, number, of, cells, dying, by, 'apoptosis,', which, was, observed, using, two, 'methods,', direct, counting, and, 'FlowSight', analysis])]). relacion([sujeto(['Simultaneously,', cell, motile, activity]), verbo([decreased]), complemento([to, the, same, degree, in, cancer, and, normal, cells, within, the, first, 8, h, of, incubation, in, the, presence, of, 9, -, 'AAA'])]). relacion([sujeto(['The', results, presented, in, the, current, study]), verbo([suggest]), complemento([that, 'short-lasting', tests, for, potential, anticancer, substances, can, be, 'insufficient;', which, may, result, in, cell, 'type-dependent', differences, in, the, responses, of, cells, to, tested, compounds, that, act, with, a, delay, being, overlooked])]). relacion([sujeto(['Main', known, mechanism, of, action, of, aminoglycosides, is, to]), verbo([inhibit]), complemento([the, protein, synthesis, by, inhibiting, the, normal, functioning, of, ribosome])]). relacion([sujeto(['Primary']), verbo([target]), complemento([of, aminoglycosides, are, the, ribosomal, 'RNA', and, its, associated, proteins])]). relacion([sujeto(['Various', mechanisms]), verbo([have]), complemento([been, proposed, for, aminoglycosides, resistance, but, still, some, are, unsolved])]). relacion([sujeto(['As', proteins, are]), verbo([involved]), complemento([in, most, of, the, biological, 'processes,', these, act, as, a, potential, diagnostic, markers, and, drug, targets])]). relacion([sujeto(['Twenty', protein, spots, were]), verbo([found]), complemento([to, have, over, expressed, in, resistant, isolates, and, were, identified])]). relacion([sujeto(['Docking', results, showed, that, 'AK', and, 'KM']), verbo([binds]), complemento([to, the, conserved, domain, '(', 'DUF,', 'USP-A,', 'Luciferase,', 'PEBP', and, 'Polyketidecyclase/dehydrase', 'domain)', of, these, hypothetical, proteins, and, over, expression, of, these, proteins, might, 'neutralize/modulate', the, effect, of, drug, molecules])]). relacion([sujeto(['String', analysis, also]), verbo([suggested]), complemento([that, over, expressed, proteins, along, with, their, interactive, partners, might, be, involved, in, aminoglycosides, resistance])]). relacion([sujeto(['Cumulative', effect, of, these, over]), verbo([expressed]), complemento([proteins, could, be, involved, in, 'AK', and, 'KM', resistance, by, mitigating, the, 'toxicity,', repression, of, drug, target, and, neutralizing, affect])]). relacion([sujeto(['Graves\'', hyperthyroidism, is]), verbo([caused]), complemento([by, autoantibodies, directed, against, the, 'thyroid-stimulating', hormone, receptor, '(', 'TSHR)', that, mimic, the, action, of, 'TSH'])]). relacion([sujeto(['The', establishment, of, 'Graves\'', hyperthyroidism, in, experimental, animals]), verbo([has]), complemento([proven, to, be, an, important, approach, to, dissect, the, mechanisms, of, 'self-tolerance', breakdown, that, lead, to, the, production, of, 'thyroid-stimulating', 'TSHR', autoantibodies, '(', 'TSAbs)'])]). relacion([sujeto([&, 'quot;Shimojo\'s', 'model"', was, the, first, successful, 'Graves\'', animal, 'model,', wherein, immunization, with, fibroblasts, cells]), verbo([expressing]), complemento(['TSHR', and, a, major, histocompatibility, complex, '(', 'MHC)', class, 'II', 'molecule,', but, not, either, 'alone,', induced, 'TSAb', production, in, 'AKR/N', '(', 'H-2(k))', mice])]). relacion([sujeto(['These', data, are, also, in, agreement, with, the, observation, that, 'Graves\'', thyrocytes, often, aberrantly]), verbo([express]), complemento(['MHC', class, 'II', antigens, via, mechanisms, that, remain, unclear])]). relacion([sujeto(['Our', group, demonstrated, that, cytosolic, 'self-genomic', 'DNA', fragments, derived, from, sterile, injured, cells, can]), verbo([induce]), complemento([aberrant, 'MHC', class, 'II', expression, and, production, of, multiple, inflammatory, cytokines, and, chemokines, in, thyrocytes, in, 'vitro,', suggesting, that, severe, cell, injury, may, initiate, immune, responses, in, a, way, that, is, relevant, to, thyroid, autoimmunity, mediated, by, cytosolic, 'DNA', signaling])]). relacion([sujeto(['This', review, focuses, on, evidence]), verbo([suggesting]), complemento([that, cell, 'injury-derived', 'self-DNA', fragments, could, act, as, 'Graves\'', disease, triggers])]). relacion([sujeto(['Genetic', improvement, of, photosynthetic, performance, of, cereal, crops, and]), verbo([increasing]), complemento([the, efficiency, with, which, solar, radiation, is, converted, into, biomass, has, recently, become, a, major, focus, for, crop, physiologists, and, breeders])]). relacion([sujeto(['The', pulse, amplitude]), verbo([modulated]), complemento([chlorophyll, fluorescence, technique, '(', 'PAM)', allows, quantitative, leaf, level, monitoring, of, the, utilization, of, energy, for, photochemical, light, conversion, and, 'photo-protection', in, natural, 'environments,', potentially, over, the, entire, crop, lifecycle])]). relacion([sujeto(['These', sites]), verbo([expressed]), complemento([the, enduring, mandate, of, the, 'Scottish', 'Poor', 'Law', 1845, over, the, domain, of, '\'', 'madness\''])]). relacion([sujeto(['Cognate', interactions, between, 'T', follicular, helper, '(', 'Tfh)', cells, and, 'B', cells, are, essential, for]), verbo([promoting]), complemento([protective, 'Ab', responses])]). relacion([sujeto(['Whereas', costimulatory, receptors, such, as, 'ICOS', are, accepted, as, being, important, for, the, induction, of, 'Tfh', cell, fate, 'decision,', other, molecules, may, play, key, roles, in, amplifying, or]), verbo([maintaining]), complemento([the, 'Tfh', phenotype])]). relacion([sujeto(['In', this, 'study,', with, vaccinia, virus, infection, in, 'mice,', we, show, that, 'OX40', was]), verbo([expressed]), complemento([on, 'Tfh', cells, that, accumulated, at, the, 'T/B', borders, in, the, white, pulp, of, the, spleen, and, that, 'OX40-dependent', signals, directly, shaped, the, magnitude, and, quality, of, the, their, response, to, viral, 'Ags'])]). relacion([sujeto(['Most', 'significantly,', we]), verbo([found]), complemento([that, sustained, interactions, between, 'OX40', and, its, 'ligand,', 'OX40L,', beyond, the, time, of, initial, encounter, with, dendritic, cells, were, required, for, the, persistence, of, high, numbers, of, 'Tfh', and, 'GC', 'B', cells])]). relacion([sujeto(['Thus,', 'OX40', and, 'ICOS']), verbo([act]), complemento([in, a, 'cooperative,', nonredundant, manner, to, maximize, and, prolong, the, 'Tfh', response, that, is, generated, after, acute, virus, infection])]). relacion([sujeto(['Malignant', features, such, as, sustained, 'proliferation,', refractoriness, to, growth, 'suppressors,', resistance, to, cell, death, or, aberrant, motility, and, metastasis, can, be]), verbo([triggered]), complemento([by, a, variety, of, mutations, and, signaling, adaptations])]). relacion([sujeto(['Signaling', nodes, can]), verbo([act]), complemento([as, 'cancer-associated', factors, by, cooperating, with, 'oncogene-governed', pathways, or, participating, in, compensatory, transduction, networks, to, strengthen, tumor, properties])]). relacion([sujeto(['Via', its, complex, network, of, connections, with, other, cellular, 'proteins,', 'GRK2', contributes, to, the, modulation, of, basic, cellular, functions, such, as, cell, 'proliferation,', survival, or, 'motility,', and, is]), verbo([involved]), complemento([in, metabolic, 'homeostasis,', inflammation, or, angiogenic, processes])]). relacion([sujeto(['Moreover,', altered, 'GRK2', levels, are, starting, to, be]), verbo([reported]), complemento([in, different, tumoral, contexts, and, shown, to, promote, breast, tumorigenesis, or, to, trigger, the, tumoral, angiogenic, switch])]). relacion([sujeto(['The', ability, to]), verbo([modulate]), complemento([several, of, the, hallmarks, of, cancer, puts, forward, 'GRK2', as, an, 'onco-modifier,', able, to, modulate, carcinogenesis, in, a, 'cell-type', specific, way])]). relacion([sujeto(['For', several, 'decades,', glucocorticoids]), verbo([have]), complemento([been, used, empirically, to, treat, rapid, progressive, 'GN'])]). relacion([sujeto(['It', is, commonly, assumed, that, glucocorticoids]), verbo([act]), complemento([primarily, by, dampening, the, immune, 'response,', but, the, mechanisms, remain, incompletely, understood])]). relacion([sujeto(['In', mice, treated, with, nephrotoxic, serum, to]), verbo([induce]), complemento([crescentic, nephritis, '(', rapidly, progressive, 'GN),', this, genetic, inactivation, of, the, 'GR', in, kidney, epithelial, cells, exerted, renal, 'benefits,', including, inhibition, of, albuminuria, and, cellular, crescent, 'formation,', similar, to, the, renal, benefits, observed, with, 'high-dose', prednisolone, in, control, mice])]). relacion([sujeto(['However,', genetic, inactivation, of, the, 'GR', in, kidney, epithelial, cells, did, not]), verbo([induce]), complemento([the, immunosuppressive, effects, observed, with, prednisolone])]). relacion([sujeto(['In', 'vitro,', prednisolone, and, the, pharmacologic, 'GR', antagonist, mifepristone, each]), verbo([acted]), complemento([directly, on, primary, cultures, of, parietal, epithelial, 'cells,', inhibiting, cellular, outgrowth, and, proliferation])]). relacion([sujeto(['Collectively,', these, data, show, that, glucocorticoids]), verbo([act]), complemento([directly, on, activated, glomerular, parietal, epithelial, cells, in, crescentic, nephritis])]). relacion([sujeto(['We', showed, that, 'J113863', and, its, enantiomer, 'UCB35625,', initially, identified, as, 'high-affinity', antagonists, for, 'CCR1', and, 'CCR3,', also]), verbo([bind]), complemento([with, low, affinity, to, the, closely, related, receptors, 'CCR2', and, 'CCR5'])]). relacion([sujeto(['Unlike', 'chemokines,', the, compounds, did, not]), verbo([activate]), complemento(['G12'])]). relacion([sujeto(['Binding', of, 'J113863', to, 'CCR2', or, 'CCR5', also]), verbo([induced]), complemento([the, recruitment, of, 'β-arrestin', 2, whereas, 'UCB35625', did, not])]). relacion([sujeto(['UCB35625']), verbo([induced]), complemento([the, chemotaxis, of, 'L1'])]). relacion([sujeto([2, cells]), verbo([expressing]), complemento(['CCR2', or, 'CCR5'])]). relacion([sujeto(['In', 'contrast,', 'J113863']), verbo([induced]), complemento([the, migration, of, 'L1'])]). relacion([sujeto([33, 'H', substitution, strongly]), verbo([increased]), complemento([the, activation, of, 'G', proteins, and, 'β-arrestin', 2, by, 'J113863'])]). relacion([sujeto(['These', results, highlight, the, biased, nature, of, the, 'J113863', and, 'UCB35625', that]), verbo([act]), complemento([either, as, 'antagonist,', partial, agonist, or, full, agonist, according, to, the, 'receptor,', the, enantiomer, considered, and, the, signaling, pathway, investigated])]). relacion([sujeto(['Transcriptional', enhancers, are, critical, for]), verbo([maintaining]), complemento([cell, 'type-specific', gene, expression, and, driving, cell, fate, changes, during, development])]). relacion([sujeto(['Highly']), verbo([transcribed]), complemento([genes, are, often, associated, with, a, cluster, of, individual, enhancers, such, as, those, found, in, locus, control, regions])]). relacion([sujeto(['Recently', these]), verbo([have]), complemento([been, termed, stretch, enhancers, or, 'super-enhancers,', which, have, been, predicted, to, regulate, critical, cell, identity, genes])]). relacion([sujeto(['Our', results]), verbo([reveal]), complemento([that, the, effect, of, deleting, 'ECs,', also, classified, as, 'ES', cell, 'super-enhancers,', is, highly, 'variable,', resulting, in, target, gene, expression, reductions, ranging, from, 12, '%', to, as, much, as, 92, '%'])]). relacion([sujeto(['Partial', deletions, of, these, 'ECs', which, removed, only, one, enhancer, or, a, 'sub-cluster', of, enhancers, revealed, partially, redundant, control, of, the]), verbo([regulated]), complemento([gene, by, multiple, enhancers, within, the, larger, cluster])]). relacion([sujeto(['Many', highly]), verbo([transcribed]), complemento([genes, in, 'ES', cells, are, not, associated, with, a, 'super-enhancer;', 'furthermore,', 'super-enhancer', predictions, ignore, 81, '%', of, the, potentially, active, regulatory, elements, predicted, by, 'co-binding', of, 5, or, more, 'pluripotency-associated', transcription, factors])]). relacion([sujeto(['In', 'addition,', select, 'super-enhancers', and, enhancers, were, identified, which]), verbo([regulated]), complemento([clusters, of, paralogous, genes])]). relacion([sujeto(['We', conclude, that, whereas, robust, transcriptional, output, can, be, achieved, by, an, isolated, 'enhancer,', clusters, of, enhancers]), verbo([acting]), complemento([on, a, common, target, gene, act, in, a, partially, redundant, manner, to, fine, tune, transcriptional, output, of, their, target, genes])]). relacion([sujeto(['The', prevalence, of, active, cigarette, smokers]), verbo([decreased]), complemento([from, 'mid-1990s', onwards, among, women, aged, '≥30', 'years,', probably, due, to, the, ban, of, cigarette, smoking, in, most, workplaces])]). relacion([sujeto(['Compared', with, 'non-smokers,', women, who, undisclosed, smoking, were, more, likely, to, be, 'young,', 'unmarried,']), verbo([have]), complemento([a, socioeconomic, status, lower, than, 'white-collar', worker, and, have, a, preterm, birth])]). relacion([sujeto(['Herbal', medicine, is, a, concoction, of, numerous, chemical, 'ingredients,', and, it, exhibits, polypharmacological, effects, to]), verbo([act]), complemento([on, multiple, pharmacological, 'targets,', regulating, different, biological, mechanisms, and, treating, a, variety, of, diseases])]). relacion([sujeto(['Thus,', this, complexity, is, impossible, to, deconvolute, by, the, reductionist, method, of, extracting, one, active, ingredient]), verbo([acting]), complemento([on, one, biological, target])]). relacion([sujeto(['To', dissect, the, polypharmacological, effects, of, herbal, medicines, and, their, underling, pharmacological]), verbo([targets]), complemento([as, well, as, their, corresponding, active, ingredients])]). relacion([sujeto(['The', myocardial, ischemia, model, was]), verbo([induced]), complemento([by, 'Ameroid', constriction, of, the, left, anterior, descending, coronary, in, 'Ba-Ma', miniature, pigs])]). relacion([sujeto(['RNA-seq', analysis, was, utilized, to]), verbo([find]), complemento([the, differential, genes, induced, by, myocardial, ischemia, in, pigs, treated, with, formula, 'QSKL'])]). relacion([sujeto(['A', 'transcriptome-based', inference, method, was, used, to]), verbo([find]), complemento([the, landmark, drugs, with, similar, mechanisms, to, 'QSKL'])]). relacion([sujeto(['Then,', based, on, the, landmark, 'drugs,', 155, potential, pharmacological]), verbo([targets]), complemento([and, 57, indications, were, identified, for, 'QSKL'])]). relacion([sujeto(['Our', results, demonstrate, the, power, of, a, combined, approach, for, exploring, the, pharmacological]), verbo([target]), complemento([and, chemical, space, of, herbal, medicines])]). relacion([sujeto(['We', hope, that, our, method, could]), verbo([enhance]), complemento([our, understanding, of, the, molecular, mechanisms, of, herbal, systems, and, further, accelerate, the, exploration, of, the, value, of, traditional, herbal, medicine, systems])]). relacion([sujeto(['Participants', were]), verbo([required]), complemento([to, meet, criteria, for, schizophrenia, and, major, depression])]). relacion([sujeto(['A', further, 'large-scale', definitive, randomised, controlled, trial, is]), verbo([required]), complemento([to, determine, effectiveness])]). relacion([sujeto(['We', evaluated, the, literature, to]), verbo([find]), complemento([out, if, these, metals, act, in, humans, as, genotoxic, carcinogens, and, if, their, health, effects, can, be, predicted, by, use, of, micronucleus, '(', 'MN)', assays, with, lymphocytes, 'and/or', with, other, genotoxicity, tests])]). relacion([sujeto(['Numerous', studies, showed, that]), verbo([lead]), complemento([and, mercury, induce, cancer, in, humans, and, also, in, 'animals,', in, vitro, experiments, with, cultured, cells, indicate, that, they, cause, 'DNA', damage, via, different, molecular, mechanisms, including, release, of, reactive, oxygen, species, and, interactions, with, 'DNA', repair, processes])]). relacion([sujeto(['Also', in, most, human, 'studies,', positive, results, were, obtained, in, 'MN', tests, with, lymphocytes, '(', all, 15, occupational, studies, with]), verbo([lead]), complemento([yielded, positive, 'results,', with, mercury, 6, out, of, 7, investigations, were, 'positive)'])]). relacion([sujeto(['For', 'cadmium,', there, is, clear, evidence, that, it]), verbo([causes]), complemento([cancer, in, 'humans;', 'however,', induction, of, chromosomal, damage, was, only, seen, in, high, dose, experiments, with, mammalian, cells, while, results, of, animal, and, human, studies, yielded, conflicting, results, '(', only, in, 2, of, 5, 'MN', trials, with, humans, positive, findings, were, 'reported)'])]). relacion([sujeto(['The', findings, of, 'MN', studies, with]), verbo([lead]), complemento([and, mercury, are, in, excellent, agreement, with, results, which, were, obtained, with, other, endpoints, '(', e])]). relacion([sujeto(['Important', future, tasks, will, be, the, realization, of, larger, studies, with, a, uniform, standardized, 'protocol,', the, additional, evaluation, of, anomalies, other, than, 'MN', '(']), verbo([nuclear]), complemento([buds, and, 'bridges)', and, the, combination, of, such, trials, with, investigations, which, allow, to, define, the, molecular, mechanisms, relevant, for, exposed, humans])]). relacion([sujeto(['It']), verbo([has]), complemento([been, suggested, that, heavy, exercise, might, increase, oxidative, 'stress,', causing, mitochondrial, 'DNA', '(', 'mtDNA)', mutations, as, well, as, 'DNA', mutations, and, changes, in, the, mtDNA, copy, number, in, cells])]). relacion([sujeto(['We', hypothesize, association, between, exercise]), verbo([induced]), complemento([oxidative, stress, and, mtDNA, damage, in, peripheral, blood, lymphocytes, '(', 'PBLs)', of, highly, trained, swimmers])]). relacion([sujeto(['Even', though, an]), verbo([increase]), complemento([in, mtDNA4977, deletion, was, found, in, all, study, 'groups,', the, difference, was, not, statistically, significant, '(', 'p=0'])]). relacion([sujeto(['The', mtDNA, copy, numbers, were]), verbo([found]), complemento([to, be, surprisingly, high, in, highly, trained, swimmers, compared, to, normal, trained, swimmers, and, 'non-athlete', subjects, by, 4.03, fold, '(', 'p=', 0.0002, ')', and, 5.58, fold, '(', 'p=0'])]). relacion([sujeto(['No', significant, differences, were]), verbo([found]), complemento([between, groups, by, means, of, intracellular, 'ATP', levels, '(', 'p=0'])]). relacion([sujeto([&, 'nbsp;', 'No', correlation, was]), verbo([found]), complemento([between, mtDNA, copy, number, and, intracellular, 'ATP', content, of, the, 'PBLs', '(', 'p=0'])]). relacion([sujeto(['Our', results]), verbo([suggest]), complemento([that, heavy, training, does, not, have, a, specific, effect, on, mtDNA4977, deletion, but, it, may, be, affecting, mitochondrial, copy, numbers, which, may, act, as, a, compensatory, mechanism, related, to, 'ATP', levels, in, blood])]). relacion([sujeto(['Australian', 'Indigenous', children, and, their, carers, '(', 'N', 1230, ')']), verbo([participating]), complemento([in, the, 'Longitudinal', 'Study', of, 'Indigenous', 'Children'])]). relacion([sujeto(['Almost', half, '(', 45, '%', ;, n, 555, /, 1230, ')', of, carers]), verbo([reported]), complemento([barriers, to, their, 'children\'s', fruit, and, vegetable, intake])]). relacion([sujeto(['Dislike', of, fruit, and, vegetables, was, the, most, common, 'barrier,']), verbo([reported]), complemento([by, 32, '·9', '%', of, 'carers;', 'however,', we, identified, few, factors, associated, with, dislike])]). relacion([sujeto(['Carers', were, more, than, ten, times, less, likely, to]), verbo([report]), complemento([barriers, to, accessing, fruit, and, vegetables, if, they, lived, large, cities, v])]). relacion([sujeto(['Within', urban, and, inner, regional, 'areas,', child, and, carer, 'well-being,', financial, 'security,', suitable, housing, and, community, cohesion]), verbo([promoted]), complemento([access, to, fruit, and, vegetables])]). relacion([sujeto(['In', this, national, 'Indigenous', 'Australian', 'sample,', almost, half, of, carers, faced, barriers, to]), verbo([providing]), complemento([their, children, with, a, healthy, diet])]). relacion([sujeto(['The', aim, of, this, study, was, to, investigate, the, effect, of, a, behavioral, intervention, of, diet, and, physical, activity, advice, on, dietary, patterns, in, obese, pregnant, woman]), verbo([participating]), complemento([in, the, 'UPBEAT', 'study,', and, to, explore, associations, of, dietary, patterns, with, pregnancy, outcomes])]). relacion([sujeto(['Four', distinct, baseline, dietary, patterns, were, 'defined;', 'Fruit', and, 'vegetables,', 'African/Caribbean,', 'Processed,', and, 'Snacks,', which, were, differently]), verbo([associated]), complemento([with, social, and, demographic, factors])]). relacion([sujeto(['In', the, adjusted, 'model,', baseline, scores, for, the, 'African/Caribbean', '(', quartile, 4, compared, with, quartile, 1, :, 'OR', =, 2.46, ;, 95, '%', 'CI', 1.41, ',', 4.3, ')', and, 'Processed', '(', quartile, 4, compared, with, quartile, 1, :, 'OR', =, 2.05, ;, 95, '%', 'CI', 1.23, ',', 3.41, ')', patterns, in, the, entire, cohort, were]), verbo([associated]), complemento([with, increased, risk, of, gestational, diabetes])]). relacion([sujeto(['African/Caribbean', and, 'Processed', patterns, were]), verbo([associated]), complemento([with, an, increased, risk, of, gestational, 'diabetes,', and, provide, potential, targets, for, future, interventions])]). relacion([sujeto(['Proteins']), verbo([involved]), complemento([in, tumor, cell, migration, can, potentially, serve, as, markers, of, invasive, disease])]). relacion([sujeto(['Activated', 'Leukocyte', 'Cell', 'Adhesion', 'Molecule', '(', 'ALCAM)']), verbo([promotes]), complemento(['adhesion,', while, shedding, of, its, extracellular, domain, is, associated, with, migration])]). relacion([sujeto(['While', 'ALCAM', mRNA, expression, was, 'unchanged,', histological, detection, of, 'ALCAM']), verbo([decreased]), complemento([with, increasing, stage, '(', 'P', =, 0.004, ')'])]). relacion([sujeto(['These', findings, demonstrate, that, markers]), verbo([reporting]), complemento([on, cell, motility, can, act, as, prognostic, indicators])]). relacion([sujeto(['Fatigue', in, hospital, nurses, is]), verbo([associated]), complemento([with, decreased, nurse, 'satisfaction,', increased, turnover, and, negative, patient, outcomes])]). relacion([sujeto(['Addressing', fatigue, in, nurses]), verbo([has]), complemento([been, identified, as, a, priority, by, many, organizations, worldwide, in, an, effort, to, promote, both, a, culture, of, patient, safety, and, a, healthy, nursing, workforce])]). relacion([sujeto(['Twenty-two', nurses, working, in, intensive, care, and, 'medical-surgical', units, within, a, large, academic, medical, center, in, the, 'United', 'States']), verbo([participated]), complemento([in, the, interviews])]). relacion([sujeto(['These', 'values,', 'beliefs,', and, behaviors, define, the, specific, aspects, of, nursing, professional, culture, that, can]), verbo([act]), complemento([as, barriers, to, fatigue, risk, management, programs, and, achieving, safety, culture, in, hospital, organizations])]). relacion([sujeto(['Nurse', fatigue, and, attributes, of, nurse, professional, culture, also]), verbo([have]), complemento([implications, for, nurse, satisfaction, and, retention])]). relacion([sujeto(['Future', work, is, needed, to, identify, and, evaluate, innovative, culture, change, models, and, strategies, to]), verbo([target]), complemento([these, barriers])]). relacion([sujeto(['Both', obesity, '(', body, mass, index, '≥', 30, ')', and, educational, attainment]), verbo([have]), complemento([increased, dramatically, in, the, 'United', 'States', since, the, 1970, s])]). relacion([sujeto(['In', the, total, 'population,', obesity]), verbo([increased]), complemento([from, 15.7, '%', to, 38.8, '%', ',', and, there, were, increases, in, the, greater, obese, probabilities, of, 'non-college', graduates, relative, to, 'four-year', college, graduates])]). relacion([sujeto(['The']), verbo([increase]), complemento([in, obesity, would, have, been, lower, by, 10, '%', '(', 2.2, percentage, 'points)', if, educational, inequalities, in, obesity, had, stayed, at, their, 1970, values, and, lower, by, one, third, '(', 7.9, 'points)', if, obesity, inequalities, had, been, eliminated])]). relacion([sujeto(['As', a, 'result,', the, impact, of, obesity, inequalities, on, the, obesity, trend, was, largest, among, white, females, '(', a, 47, '%', reduction, in, the, obesity]), verbo([increase]), complemento([if, obesity, inequalities, had, been, 'eliminated),', and, virtually, zero, among, black, males])]). relacion([sujeto(['On', the, other, 'hand,', without, educational, 'improvements,', the, obesity]), verbo([increase]), complemento([would, have, been, 9, '%', more, in, the, total, 'population,', 23, '%', more, among, white, females, and, not, different, in, the, other, three, subpopulations])]). relacion([sujeto(['Results', indicate, that, obesity, inequalities, made, sizable, contributions, to, the, obesity, 'trends,', and, the, obesity, reductions]), verbo([associated]), complemento([with, educational, improvements, were, more, limited])]). relacion([sujeto(['Only', '~15%', of, repeats, are, present, in, any, known, functional, 'domain,', while, '~74%', of, repeats, are, present, in, the, disordered, 'regions,']), verbo([suggesting]), complemento([that, 'SAARs', add, to, the, functionality, of, proteins, by, providing, 'flexibility,', stability, and, act, as, linker, elements, between, domains])]). relacion([sujeto(['Comparison', of, 'SAAR', containing, proteins, across, species]), verbo([reveals]), complemento([that, while, shorter, repeats, are, conserved, among, 'orthologs,', proteins, with, longer, 'repeats,', &, 'gt;15', amino, 'acids,', are, unique, to, the, respective, organism])]). relacion([sujeto(['Lysine', repeats, are, well]), verbo([conserved]), complemento([among, orthologs, with, respect, to, their, length, and, number, of, occurrences, in, a, protein])]). relacion([sujeto(['Other', amino, acids, such, as, glutamic, 'acid,', 'proline,', serine, and, alanine, repeats, are, generally]), verbo([conserved]), complemento([among, the, orthologs, with, varying, repeat, lengths])]). relacion([sujeto(['These', findings]), verbo([suggest]), complemento([that, 'SAARs', have, accumulated, in, the, proteome, under, positive, selection, pressure, and, that, they, provide, flexibility, for, optimal, folding, of, 'functional/structural', domains, of, proteins])]). relacion([sujeto(['Trust']), verbo([has]), complemento([been, considered, the, &, 'quot;cement"', of, a, society, and, is, much, studied, in, sociology, and, other, social, sciences])]). relacion([sujeto(['Most', 'studies,', 'however,']), verbo([have]), complemento([neglected, one, important, aspect, of, 'trust:', it, involves, an, act, of, forgiving, and, showing, tolerance, toward, 'another\'s', failure])]). relacion([sujeto(['First,', we, introduce, two, types, of, 'uncertainties:', uncertainty, as, to, whether, trustees]), verbo([have]), complemento([the, intention, to, 'cooperate,', and, uncertainty, as, to, whether, trustees, have, enough, competence, to, accomplish, the, entrusted, tasks])]). relacion([sujeto(['Second,', we, examine, the, manner, in, which, trust, functions, in, a, broader, social, 'context,', one, that]), verbo([involves]), complemento([matching, and, commitment, processes])]). relacion([sujeto(['Second,', we, investigate, socially, embedded, trust, relationships, in, contexts]), verbo([involving]), complemento([the, matching, and, commitment, 'processes,', using, 'agent-based', simulation])]). relacion([sujeto(['However,', all, drugs]), verbo([targeting]), complemento([these, receptors, bind, to, the, extracellular, 'ligand-binding', domain, of, the, 'receptors,', which, inherently, is, associated, with, perturbation, of, the, basic, physiological, action])]). relacion([sujeto(['Here', we, pursue, a, fundamentally, different, 'approach,', by, instead]), verbo([targeting]), complemento([the, intracellular, 'receptor-gephyrin', interaction])]). relacion([sujeto(['Finally,', we, demonstrate, that, the, gephyrin, 'super-binding', peptides]), verbo([act]), complemento([as, acute, intracellular, modulators, of, fast, synaptic, inhibition, by, modulating, receptor, 'clustering,', thus, being, conceptually, novel, modulators, of, inhibitory, neurotransmission])]). relacion([sujeto(['This']), verbo([report]), complemento([demonstrates, a, unique, case, of, conjunctival, melanoma, harboring, a, 'BRAF', 'V600E', mutation, responsive, to, systemic, therapy, with, 'BRAF', and, 'MEK', inhibitors])]). relacion([sujeto(['While', systemic, therapy, would, not, be, appropriate, in, patients, with, local, disease, 'alone,', it, may]), verbo([act]), complemento([therapeutically, in, cases, of, higher, stage, ocular, surface, and, eyelid, melanoma])]). relacion([sujeto(['Improving', patient, care, through]), verbo([enhanced]), complemento([electronic, communication, among, health, care, providers, is, aimed, at, reducing, the, number, of, medication, and, medical, errors])]). relacion([sujeto(['In', addition, to, 'ARRA,', 'Congress', presented, another, initiative, to, further, advance, the, delivery, of, 'high-quality', health, 'care,', the, 'Health', 'Information', 'Technology', for, 'Economic', and, 'Clinical', 'Health', 'Act', '(', 'HITECH),']), verbo([leading]), complemento([to, the, authorization, of, '$27', billion, to, encourage, health, care, providers, to, achieve, meaningful, use, of, the, electronic, health, record])]). relacion([sujeto(['However,', the, conversion, of, the, paper, medical, records, to, an, electronic, version]), verbo([has]), complemento([been, 'challenging,', particularly, in, specialty, departments])]). relacion([sujeto(['A', project, 'plan,', developed, in, 2009, prior, to, the, electronic, medical, record, going, 'live,']), verbo([involved]), complemento([a, multidisciplinary, 'team,', consisting, of, 'providers,', 'nurses,', and, information, system, builders, who, came, together, to, determine, how, to, capture, the, totality, of, the, burn, unit, documentation])]). relacion([sujeto(['The', goal, of, the, project, was, to, develop, an, electronic, documentation, tool, and]), verbo([provide]), complemento([a, system, to, accurately, and, efficiently, evaluate, documentation, compliance, with, the, staff])]). relacion([sujeto(['This', tool]), verbo([has]), complemento([been, regarded, by, most, health, care, organizations, as, being, the, most, accurate, in, measuring, the, extent, and, degree, of, the, burn])]). relacion([sujeto(['The', electronic, version, and, availability, of, the, tool]), verbo([increased]), complemento([compliance, to, 100, '%', in, the, fourth, quarter, of, 2015])]). relacion([sujeto(['Glioblastoma', multiforme, '(', 'GBM)', continues, to, be]), verbo([associated]), complemento([with, a, dismal, prognosis, despite, aggressive, treatment])]). relacion([sujeto(['Nanoparticles', can]), verbo([act]), complemento([directly, on, cancer, cells, or, as, drug, carriers, to, enhance, the, cancer, therapeutic, effect])]). relacion([sujeto(['They', also, showed, the, ability, to]), verbo([enhance]), complemento([the, 'drug-sensitivity', of, 'TMZ', on, 'U251', cells])]). relacion([sujeto(['Our', results, revealed, that, 'AgNPs', could]), verbo([have]), complemento([a, potential, application, in, enhancing, chemotherapy, for, glioma])]). relacion([sujeto(['Taking', their, inspiration, from, a, case, 'history,', the, authors, explore, the, effects, of, a, writing, workshop]), verbo([led]), complemento([by, a, professional, writer, for, patients, in, a, psychiatric, hospital])]). relacion([sujeto(['This', workshop, allowed, different, modes, of, transference, to, 'unfold:', transference, to, the, 'analyst-therapist,', transference, to, the, writer, who]), verbo([led]), complemento([the, 'workshop,', and, transference, to, the, other, members, of, the, group])]). relacion([sujeto(['The', writing, activity, created, conditions, in, which, there, could, be, a, movement, from, hallucination, to, 'delusion-a', delusion]), verbo([expressed]), complemento([in, fiction, through, the, act, of, writing])]). relacion([sujeto(['The', packaging, of, genetic, information, in, form, of, chromatin, within, the, nucleus]), verbo([provides]), complemento([cells, with, the, ability, to, store, and, protect, massive, amounts, of, information, within, a, compact, space])]). relacion([sujeto(['Storing', information, within, chromatin, allows, selective, access, to, specific, 'DNA', sequences, by]), verbo([regulating]), complemento([the, various, levels, of, chromatin, structure, from, 'nucleosomes,', to, chromatin, 'fibers,', loops, and, topological, associating, domains, '(', 'TADs)', using, mechanisms, that, are, being, progressively, unravelled])]). relacion([sujeto(['However,', a, relatively, unexplored, aspect, is, the, energetic, cost, of, changing, the, chromatin, configuration, to]), verbo([gain]), complemento([access, to, 'DNA', information])]). relacion([sujeto(['Among', the, enzymes, responsible, for]), verbo([regulating]), complemento([chromatin, access, are, the, 'ATP-dependent', chromatin, remodellers, that, act, on, nucleosomes, and, use, the, energy, of, 'ATP', hydrolysis, to, make, chromatin, 'DNA', more, accessible])]). relacion([sujeto(['It', is, assumed, that, the, 'ATP', used, by, these, enzymes, is]), verbo([provided]), complemento([by, the, mitochondria, or, by, cytoplasmic, glycolysis])]). relacion([sujeto(['We', hypothesize, that, though, this, may, be, the, case, for, cells, in, steady, 'state,', when, gene, expression]), verbo([has]), complemento([to, be, globally, reprogramed, in, response, to, externals, signals, or, stress, 'conditions,', the, cell, directs, energy, production, to, the, cell, 'nucleus,', where, rapid, chromatin, reorganization, is, needed, for, cell, survival])]). relacion([sujeto(['We', discovered, that, in, response, to, hormones, a]), verbo([nuclear]), complemento(['ATP', synthesis, mechanism, is, activated, that, utilizing, 'ADP-ribose', and, pyrophosphate, as, substrates])]). relacion([sujeto(['(', 1, ')', 'This', extra, view, aims, to, put, this, process, within, its, historical, 'context,', to, describe, the, enzymatic, steps, in, 'detail,', to, propose, a, possible, structure, of, the, 'ATP', synthesising, 'enzyme,', and, to, shed, light, on, how, this, may, link, to, other, reactions, within, the, cell]), verbo([providing]), complemento([a, perspective, for, future, lines, of, investigation])]). relacion([sujeto(['Sleep', spindles]), verbo([act]), complemento([as, a, powerful, marker, of, individual, differences, in, cognitive, ability])]). relacion([sujeto(['While', some, studies]), verbo([have]), complemento([specifically, demonstrated, the, relationship, between, sleep, spindles, and, intelligence, in, young, 'children,', our, previous, work, in, older, subjects, revealed, sex, differences, in, the, sleep, spindle, correlates, of, 'IQ,', which, was, never, investigated, in, small, children, before])]). relacion([sujeto(['Determining', the, extent, of, the, impact, that, consanguinity, impose, upon, the, progeny, paves, the, way, for, convincing, healthcare, policy, makers, in, highly, consanguineous, communities, to]), verbo([act]), complemento([more, diligently, in, informing, the, masses, about, the, consequences, of, practicing, inbreeding])]). relacion([sujeto(['Atmospheric', 'CO2', enrichment, is, expected, to, often, benefit, plant, 'growth,', despite]), verbo([causing]), complemento([global, warming, and, nitrogen, '(', 'N)', dilution, in, plants])]). relacion([sujeto(['Most', plants, primarily, procure, 'N', as, inorganic, nitrate, '(', 'NO3(-)', ')', or, ammonium, '(', 'NH4(+)', ')', ',', using, 'membrane-localized', transport, proteins, in, 'roots,', which, are, key]), verbo([targets]), complemento([for, improving, 'N', use])]). relacion([sujeto(['Though', interactive, effects, of, elevated, 'CO2', ',', chronic, 'warming,', and, 'N', form, on, 'N', relations, are, 'expected,', these]), verbo([have]), complemento([not, been, studied])]). relacion([sujeto(['Elevated', 'CO2', plus, chronic, warming, severely]), verbo([inhibited]), complemento([plant, 'growth,', regardless, of, 'N', 'form,', while, individually, they, had, smaller, effects, on, growth])]). relacion([sujeto(['Although', '%', 'N', in, roots, was, similar, among, all, 'treatments,', elevated, 'CO2', plus, warming]), verbo([decreased]), complemento(['(', 1, ')', 'N', uptake, rate, by, 'roots,', '(', 2, ')', total, protein, concentration, in, 'roots,', indicating, an, inhibition, of, 'N', 'assimilation,', and, '(', 3, ')', shoot, '%', 'N,', indicating, a, potential, inhibition, of, 'N', translocation, from, roots, to, shoots])]). relacion([sujeto(['Under', elevated, 'CO2', plus, 'warming,', reduced, 'NO3(-)', uptake, rate, per, g, root, was, correlated, with, a]), verbo([decrease]), complemento([in, the, concentration, of, 'NO3(-)', -, uptake, proteins, per, g, 'root,', reduced, 'NH4(+)', uptake, was, correlated, with, decreased, activity, of, 'NH4(+)', -, uptake, 'proteins,', and, reduced, 'N', assimilation, was, correlated, with, decreased, concentration, of, 'N-assimilatory', proteins])]). relacion([sujeto(['These', results, indicate, that, elevated, 'CO2', and, chronic, warming, can]), verbo([act]), complemento([synergistically, to, decrease, plant, 'N', uptake, and, 'assimilation;', 'hence,', future, global, warming, may, decrease, both, plant, growth, and, food, quality, '(', '%', 'N)'])]). relacion([sujeto(['Active,', nationally, 'representative,', public, health, surveillance, in, 58, 'EDs', located, in, the, 'United', 'States', and]), verbo([participating]), complemento([in, the, 'National', 'Electronic', 'Injury', 'Surveillance', 'System-Cooperative', 'Adverse', 'Drug', 'Event', 'Surveillance', project])]). relacion([sujeto(['Since', 2005, -, 2006, ',', the, proportions, of, 'ED', visits, for, adverse, drug, events, from, anticoagulants, and, diabetes, agents]), verbo([have]), complemento(['increased,', whereas, the, proportion, from, antibiotics, has, decreased])]). relacion([sujeto(['Of', all, the, 'employment-related', actions, taken, by, 'employers,', the]), verbo([act]), complemento([of, termination, creates, the, greatest, risk, of, legal, liability])]). relacion([sujeto(['Many', claims, of, employment, discrimination, filed, with, the, 'Equal', 'Employment', 'Opportunity', 'Commission', arise, from, the]), verbo([act]), complemento([of, termination])]). relacion([sujeto(['However,', most, employees, sue, because, they]), verbo([have]), complemento([lost, their, job, or, fear, they, will, lose, their, job])]). relacion([sujeto(['Because', these, individuals]), verbo([have]), complemento([virtually, nothing, to, 'lose,', they, often, see, filing, a, claim, with, the, 'Equal', 'Employment', 'Opportunity', 'Commission', or, filing, a, lawsuit, as, the, only, viable, 'option-often', suing, for, wrongful, discharge])]). relacion([sujeto(['The', infection]), verbo([caused]), complemento([by, the, zoonotic, opportunistic, pathogen, 'Mycobacterium', avium, subsp])]). relacion([sujeto([hominissuis, '(', 'Mah)', was]), verbo([reported]), complemento([for, the, first, time, in, a, pet, ferret])]). relacion([sujeto(['Ferrets', can]), verbo([act]), complemento([as, reservoirs, of, mycobacteria, exposing, their, owners, to, the, 'infection,', which, is, of, major, concern, in, immunodeficient, 'individuals,', as, those, 'HIV-infected'])]). relacion([sujeto(['Mosquitoes']), verbo([act]), complemento([as, vectors, of, devastating, pathogens, and, 'parasites,', representing, a, key, threat, for, millions, of, humans, and, animals, worldwide])]). relacion([sujeto(['We', proposed, a, novel, method, of, 'fern-mediated', biosynthesis, of, silver, nanoparticles, '(', 'AgNP)', using, 'Dicranopteris', 'linearis,']), verbo([acting]), complemento([as, a, reducing, and, capping, agent])]). relacion([sujeto([linearis, extract, and, 'AgNP', '(', 10, '×LC50)']), verbo([led]), complemento([to, 100, '%', larval, reduction, after, 72, h])]). relacion([sujeto(['(', 'Chrysobalanaceae)']), verbo([has]), complemento([been, used, for, the, treatment, of, abdominal, pain, and, cramps])]). relacion([sujeto([')', '(', group, with, 7, -, 8, 'mice)', and, the, analgesic, profile, was, assessed, employing, the, acetic, 'acid-induced', 'writhing,', 'formalin,', hot, plate, tests, and, hyperalgesia]), verbo([induced]), complemento([by, carrageenan, '(', 'CG)', or, tumour, necrosis, 'factor-alpha'])]). relacion([sujeto(['Our', results]), verbo([suggest]), complemento([that, 'AEC', act, against, inflammatory, pain])]). relacion([sujeto(['Building', upon, the, 'Foucauldian', insight, that, sexuality, is, a, discourse, and, thereby, refusing, to, be, chained, to, the, 'Freudian', repressive, 'hypothesis,', this, paper, aims, to, ascertain, how, the, closet, is, made, and, how, the, homosexual, comes, to, be, seen, in, the]), verbo([act]), complemento([of, reading, the, literary, 'text,', &, 'quot;The', 'Beast', in, the, 'Jungle,"', written, by, 'Henry', 'James'])]). relacion([sujeto(['The', antitumoral, effect, of, 'D-Fraction']), verbo([has]), complemento([long, been, exclusively, attributed, to, their, immunostimulatory, capacity])]). relacion([sujeto(['However,', in, recent, years]), verbo([increasing]), complemento([evidence, showed, that, 'D-Fraction', directly, affects, the, viability, of, canine, and, human, tumor, 'cells,', independent, of, the, immune, system])]). relacion([sujeto(['Previously,', we]), verbo([have]), complemento([reported, that, 'D-Fraction', modulates, the, expression, of, genes, associated, with, cell, 'proliferation,', cell, 'death,', 'migration,', 'invasion,', and, metastasis, in, 'MCF7', human, breast, cancer, cells])]). relacion([sujeto(['Therefore,', the, purpose, of, the, current, study, is, to, investigate, if, this, modulation, of, gene, expression, by, 'Maitake', 'D-Fraction', really]), verbo([modulates]), complemento([tumor, progression])]). relacion([sujeto(['In', the, present, 'work,', we, demonstrate, for, the, first, time, that, 'Maitake', 'D-Fraction', is, able, to]), verbo([act]), complemento([directly, on, mammary, tumor, 'cells,', modulating, different, cellular, processes, involved, in, the, development, and, progression, of, cancer])]). relacion([sujeto(['We', demonstrate, that, 'D-Fraction']), verbo([decreases]), complemento([cell, 'viability,', increases, cell, 'adhesion,', and, reduces, the, migration, and, invasion, of, mammary, tumor, 'cells,', generating, a, less, aggressive, cell, behavior])]). relacion([sujeto(['In', concordance, with, these, 'results,', we, also, demonstrate, that, 'D-Fraction']), verbo([decreases]), complemento([tumor, burden, and, the, number, of, lung, metastases, in, a, murine, model, of, breast, cancer])]). relacion([sujeto(['It', was]), verbo([found]), complemento([that, the, synthetic, analog, dihydroavenanthramide, 'D', '(', 'DHAvD)', can, interact, with, the, 'neurokinin-1', receptor, '(', 'NK1R)', and, inhibit, mast, cell, degranulation])]). relacion([sujeto(['Our', findings, indicate, that, 'DHAvD', may]), verbo([act]), complemento([as, a, 'NK1R', inhibitor, and, could, be, a, promising, candidate, for, topical, treatments, of, chronic, pruritus])]). relacion([sujeto(['We', used, small, palladium, clusters, to]), verbo([act]), complemento([as, the, catalyst, supported, on, the, substrate, '(', comprised, of, pyridinic, and, pyrrolic, nitrogen, doped, 'graphene),', in, order, to, study, hydrogen, 'dissociation,', migration, and, diffusion])]). relacion([sujeto(['Charge', transfer, and, strong]), verbo([binding]), complemento([between, the, catalyst, and, the, substrate, lead, to, dissociated, states, of, 'H2', and, prevent, clusters, from, detaching, and, coalescing])]). relacion([sujeto(['Subsequently,', it, was]), verbo([found]), complemento([that, thermal, desorption, does, not, limit, chemisorbed, hydrogen, diffusion, on, the, substrate])]). relacion([sujeto(['This', work, may, thus, help, to, determine, experimental, strategies, with, the, capacity, to]), verbo([enhance]), complemento([hydrogen, storage])]). relacion([sujeto(['Structural', details]), verbo([provide]), complemento([new, insights, into, 'sub-steps', during, the, catalysis, of, peroxide, 'reduction,', enabling, the, transition, from, an, 'FF', to, a, 'LU', conformation])]). relacion([sujeto(['Complementary', to, mutational, and, enzymatic, 'results,', these, data, unravel, the, essential, role, of, the, 'C-terminal', tail, of, bacterial, 'Prxs', to]), verbo([act]), complemento([as, a, molecular, 'switch,', mediating, the, transition, from, an, 'FF', to, a, 'LU', state])]). relacion([sujeto(['In', 'addition,', we, propose, that, the, 'C-terminal', tail]), verbo([has]), complemento([influence, on, the, propensity, of, the, disulphide, bond, 'formation,', indicating, that, as, a, consequence, on, the, robustness, and, sensitivity, to, 'over-oxidation'])]). relacion([sujeto(['Epigenetic', inactivation, of, 'GPX3']), verbo([has]), complemento([been, identified, in, various, cancers, including, leukemia])]). relacion([sujeto(['Moreover,', aberrant, 'DNA', methylation, was, also]), verbo([found]), complemento([as, a, dominant, mechanism, of, disease, progression, in, myelodysplastic, syndrome, '(', 'MDS)'])]). relacion([sujeto(['Moreover,', 'Cox', regression, analysis, revealed, that, 'GPX3', methylation, might]), verbo([act]), complemento([as, an, independent, prognostic, indicator, in, 'MDS', '(', 'HR = 1'])]). relacion([sujeto(['GPX3', methylation, density, was, significantly]), verbo([increased]), complemento([during, the, progression, from, 'MDS', to, secondary, acute, myeloid, leukemia, '(', 'sAML)', in, three, 'follow-up', paired, patients])]). relacion([sujeto(['Our', study, concludes, that, 'GPX3', methylation, in, bone, marrow, is]), verbo([associated]), complemento([with, adverse, prognosis, and, leukemia, transformation, in, 'MDS'])]). relacion([sujeto(['We', identified, research, areas, where, limited, process, knowledge]), verbo([prevents]), complemento([inclusion, of, physiological, phenomena, in, current, 'TBMs', and, research, areas, where, data, are, urgently, needed, for, model, parameterization, or, evaluation])]). relacion([sujeto(['We']), verbo([provide]), complemento([a, roadmap, for, new, science, needed, to, improve, the, representation, of, photosynthesis, in, the, next, generation, of, terrestrial, biosphere, and, 'Earth', system, models])]). relacion([sujeto(['There', are, two, types, of, cryptochromes, in, the, animal, 'kingdom:', 'Drosophila-like', 'CRYs', that]), verbo([act]), complemento([as, 'non-visual', photopigments, linking, circadian, rhythms, to, the, environmental, 'light/dark', 'cycle,', and, 'vertebrate-like', 'CRYs', that, do, not, appear, to, sense, light, 'directly,', but, control, the, generation, of, circadian, rhythms, by, acting, as, transcriptional, repressors])]). relacion([sujeto(['Some', animals]), verbo([have]), complemento([both, types, of, 'CRYs,', while, others, possess, only, one])]). relacion([sujeto(['Cryptochromes']), verbo([have]), complemento([two, 'domains,', the, photolyase, homology, region, '(', 'PHR)', and, an, 'extended,', intrinsically, disordered, 'C-terminus'])]). relacion([sujeto(['Recently,', cryptochrome, function]), verbo([has]), complemento([been, shown, to, extend, beyond, its, pivotal, role, in, circadian, 'clocks,', participating, in, regulation, of, the, 'DNA', damage, 'response,', cancer, 'progression,', and, glucocorticoid, 'signaling,', as, well, as, being, implicated, as, possible, magnetoreceptors])]). relacion([sujeto(['In', this, 'review,', we]), verbo([provide]), complemento([a, historical, perspective, on, the, discovery, of, animal, 'cryptochromes,', examine, similarities, and, differences, of, the, two, types, of, animal, 'cryptochromes,', and, explore, some, of, the, divergent, roles, for, this, class, of, proteins])]). relacion([sujeto(['Recently', we]), verbo([have]), complemento([shown, that, celastrol, prevents, 'Cd-induced', neuronal, cell, death, partially, by, suppressing, 'Akt/mTOR', pathway])]). relacion([sujeto(['Celastrol']), verbo([prevented]), complemento(['Cd-induced', neuronal, apoptosis, by, inhibiting, 'Akt-mediated', mTOR, 'pathway,', as, inhibition, of, 'Akt', with, 'Akt', inhibitor, 'X', or, ectopic, expression, of, dominant, negative, 'Akt', reinforced, 'celastrol\'s', prevention, of, 'Cd-induced', phosphorylation, of, 'S6K1/4E-BP1', and, cell, apoptosis])]). relacion([sujeto(['Furthermore,', chelating, intracellular, 'Ca(2+)', with, 'BAPTA/AM', or]), verbo([preventing]), complemento(['[', 'Ca(2+)', ']', i, elevation, using, 'EGTA', potentiated, 'celastrol\'s', repression, of, 'Cd-induced', '[', 'Ca(2+)', ']', i, elevation, and, consequential, activation, of, 'Akt/mTOR', pathway, and, cell, apoptosis])]). relacion([sujeto(['Moreover,', celastrol, blocked, 'Cd-elicited', phosphorylation, of, 'CaMKII,', and, pretreatment, with, 'BAPTA/AM', or, 'EGTA']), verbo([enhanced]), complemento(['celastrol\'s', suppression, of, 'Cd-increased', phosphorylation, of, 'CaMKII', in, neuronal, 'cells,', implying, that, celastrol, hinders, '[', 'Ca(2+)', ']', i, -, mediated, 'CaMKII', phosphorylation])]). relacion([sujeto(['Taken', 'together,', these, data, demonstrate, that, celastrol, attenuates, 'Cd-induced', neuronal, apoptosis, via]), verbo([inhibiting]), complemento(['Ca(2+)', -, 'CaMKII-dependent', 'Akt/mTOR', pathway])]). relacion([sujeto(['Our', findings, underscore, that, celastrol, may]), verbo([act]), complemento([as, a, neuroprotective, agent, for, the, prevention, of, 'Cd-induced', neurodegenerative, disorders])]). relacion([sujeto(['Clostridium', difficile]), verbo([causes]), complemento(['nosocomial/antibiotic-associated', diarrhoea, and, pseudomembranous, colitis])]). relacion([sujeto(['The', major, virulence, factors, are, toxin, 'A', and, toxin, 'B', '(', 'TcdB),', which, inactivate, 'GTPases', by, 'monoglucosylation,']), verbo([leading]), complemento([to, cytopathic, '(', cytoskeleton, 'alteration,', cell, 'rounding)', and, cytotoxic, effects, '(', 'cell-cycle', 'arrest,', 'apoptosis)'])]). relacion([sujeto([difficile, toxins, breaching, the, intestinal, epithelial, barrier, can]), verbo([act]), complemento([on, underlying, 'cells,', 'enterocytes,', 'colonocytes,', and, enteric, 'neurons,', as, described, in, vitro, and, in, 'vivo,', but, until, now, no, data, have, been, available, on, enteric, glial, cell, '(', 'EGC)', susceptibility])]). relacion([sujeto(['EGCs', are, crucial, for]), verbo([regulating]), complemento([the, enteric, nervous, 'system,', gut, 'homeostasis,', the, immune, and, inflammatory, 'responses,', and, digestive, and, extradigestive, diseases])]). relacion([sujeto(['TcdB']), verbo([induces]), complemento([the, following, in, 'EGCs:', '(', 1, ')', early, cell, rounding, with, 'Rac1', 'glucosylation;', '(', 2, ')', early, 'G2/M', 'cell-cycle', arrest, by, cyclin, 'B1/Cdc2', complex, inactivation, caused, by, p27, 'upregulation,', the, downregulation, of, cyclin, 'B1', and, 'Cdc2', phosphorylated, at, 'Thr161', and, 'Tyr15;', and, '(', 3, ')', apoptosis, by, a, 'caspase-dependent', but, 'mitochondria-independent', pathway])]). relacion([sujeto(['Most', 'importantly,', the, stimulation, of, 'EGCs', with, 'TNF-α', plus, 'IFN-γ', 'before,', concomitantly, or, after, 'TcdB', treatment, strongly]), verbo([increased]), complemento(['TcdB-induced', apoptosis])]). relacion([sujeto(['Furthermore,', 'EGCs', that, survived, the, cytotoxic, effect, of, 'TcdB', did, not, recover, completely, and, showed, not, only, persistent, 'Rac1', 'glucosylation,', 'cell-cycle']), verbo([arrest]), complemento([and, low, apoptosis, but, also, increased, production, of, glial, 'cell-derived', neurotrophic, 'factor,', suggesting, 'self-rescuing', mechanisms])]). relacion([sujeto(['In', 'conclusion,', the, high, susceptibility, of, 'EGCs', to, 'TcdB', in, 'vitro,', the]), verbo([increased]), complemento([sensitivity, to, inflammatory, cytokines, related, to, apoptosis, and, the, persistence, of, altered, functions, in, surviving, cells, suggest, an, important, in, vivo, role, of, 'EGCs', in, the, pathogenesis, of, 'C'])]). relacion([sujeto(['Sodium', hypochlorite, '(', 'NaOCl),', the, most, commonly, used, 'irrigant,']), verbo([has]), complemento([many, potential, properties, like, its, unique, ability, to, dissolve, pulp, 'tissue,', excellent, antimicrobial, 'activity,', but, has, a, cytotoxic, effect, when, injected, into, periapical, tissues])]). relacion([sujeto(['Facultative', organisms, such, as, 'Enterococcus', faecalis, and, aerobes, like, 'Staphylococcus', aureus, are, considered, to, be, the, most, resistant, species, and, one, of, the, possible]), verbo([causes]), complemento([of, root, canal, treatment, failure])]). relacion([sujeto(['So', there, is, a, need, to]), verbo([find]), complemento([an, alternative, to, sodium, hypochlorite, to, act, against, these, resistant, microorganisms])]). relacion([sujeto(['It']), verbo([has]), complemento([been, used, in, many, tissue, types, as, an, adjunct, or, replacement, for, frozen, 'section/', intra, operative, consultation])]). relacion([sujeto(['We', conclude, that, scrape, cytology, can]), verbo([act]), complemento([as, a, useful, adjunct, to, 'FNAC', and, is, a, good, procedure, for, 'intra-operative', consultation])]). relacion([sujeto(['This', case]), verbo([report]), complemento([summarizes, the, first, use, of, intravenous, vitamin, 'C', employed, as, an, adjunctive, interventional, agent, in, the, therapy, of, recurrent, acute, respiratory, distress, syndrome, '(', 'ARDS)'])]). relacion([sujeto(['The', patient, became, recurrently, septic, with, 'Gram', positive, cocci, which]), verbo([led]), complemento([to, two, instances, of, 'ARDS'])]). relacion([sujeto(['This']), verbo([report]), complemento([describes, the, 'broad-based', general, critical, care, of, a, septic, patient, with, acute, respiratory, failure, that, includes, fluid, 'resuscitation,', 'broad-spectrum', 'antibiotics,', and, vasopressor, support])]). relacion([sujeto(['Vitamin', 'C', when, used, as, a, parenteral, agent, in, high, doses]), verbo([acts]), complemento([&, 'quot;pleiotropically"', to, attenuate, proinflammatory, mediator, 'expression,', to, improve, alveolar, fluid, 'clearance,', and, to, act, as, an, antioxidant])]). relacion([sujeto(['Despite', decades, of, 'studying,', the, mechanisms]), verbo([maintaining]), complemento([high, diversity, in, the, genes, of, the, 'Major', 'Histocompatibility', 'Complex', '(', 'MHC)', are, still, puzzling, scientists])]). relacion([sujeto(['In', addition, to, pathogen, recognition, and, other, 'functions,', 'MHC', molecules, may]), verbo([act]), complemento([prenatally, in, mate, choice, and, in, 'maternal-foetal', interactions])]). relacion([sujeto(['These', interactions, are, potential, selective, mechanisms, that]), verbo([increase]), complemento([genetic, diversity, in, the, 'MHC'])]). relacion([sujeto(['During', 'pregnancy,', immune, response]), verbo([has]), complemento([a, dual, 'role:', the, foetus, represents, foreign, tissue, compared, to, 'mother,', but, 'histo-incompatibility', is, required, for, successful, pregnancy])]). relacion([sujeto(['We']), verbo([have]), complemento([studied, the, prenatal, selection, in, 'MHC', class, 'II', loci, '(', 'DLA-DQA1,', 'DLA-DQB1', and, 'DLA-DRB1)', in, domestic, dogs, by, comparing, the, observed, and, expected, offspring, genotype, proportions, in, 110, dog, families])]). relacion([sujeto(['Several', potential, selection]), verbo([targets]), complemento([were, 'addressed,', including, the, 'peptide-binding', 'site,', the, 'MHC', 'locus,', 'three-locus', haplotype, and, supertype, levels])]). relacion([sujeto(['In', 'addition,', if, the, father, shared, a, 'DLA-DRB1', allele, with, the, 'mother,', that, allele, was, inherited, by, the, offspring, more, frequently, than, 'expected,']), verbo([suggesting]), complemento([the, selective, advantage, of, a, 'histo-compatible', 'foetus,', in, contrast, to, our, expectations])]). relacion([sujeto(['But', due, to, no, indication, of, selection, at, 'locus,', 'three-locus,', or, supertype, 'levels,', we, estimated, that, the, prenatal, selection, coefficient, is, less, than, 0.3, in, domestic, dogs, and, very, likely, other, factors, are, more, important, in]), verbo([maintaining]), complemento([the, genetic, diversity, in, 'MHC', loci])]). relacion([sujeto(['Autism', spectrum, disorder, '(', 'ASD)', is, a, developmental, condition, that, affects, approximately, four, times, as, many, males, as, 'females,', a, strong, sex, bias, that]), verbo([has]), complemento([not, yet, been, fully, explained])]). relacion([sujeto(['Understanding', the]), verbo([causes]), complemento([of, this, biased, prevalence, may, highlight, novel, avenues, for, treatment, development, that, could, benefit, patients, with, diverse, genetic, 'backgrounds,', and, the, expertise, of, sex, differences, researchers, will, be, invaluable, in, this, endeavor])]). relacion([sujeto(['Though', males, consistently, outnumber, females, in, 'ASD', prevalence, 'studies,', prevalence, estimates, generated, using, different, approaches]), verbo([report]), complemento(['male/female', ratios, of, variable, magnitude, that, suggest, that, ascertainment, or, diagnostic, biases, may, contribute, to, the, male, skew, in, 'ASD'])]). relacion([sujeto(['Lastly,', 'I', describe, work, investigating, several, 'sex-differential', biological, factors, and, pathways, that, may, be, responsible, for, 'females\'', protection, 'and/or', 'males\'']), verbo([increased]), complemento([risk, predicted, by, the, 'female protective', effect, 'model,', including, sex, steroid, hormone, exposure, and, regulation, and, 'sex-differential', activity, of, certain, neural, cell, types])]). relacion([sujeto(['However,', much, future, work, from, both, the, 'ASD', and, sex, differences, research, communities, will, be]), verbo([required]), complemento([to, flesh, out, our, understanding, of, how, these, factors, act, to, influence, the, developing, brain, and, modulate, 'ASD', risk])]). relacion([sujeto(['We']), verbo([found]), complemento([that, 'XZ166', responded, to, high, 'NaCl', concentration, '(', 200, 'mM)', with, more, 'HsCBL8', transcripts, than, 'CM72,', a, cultivated, barley, line, known, for, salinity, tolerance])]). relacion([sujeto(['Notably,', 'HsCBL8', did, not]), verbo([act]), complemento([on, some, genes, downstream, of, the, rice, 'CBL', family, 'genes,', suggesting, an, interesting, interaction, between, 'HsCBL8', and, unknown, factors, to, be, further, investigated])]). relacion([sujeto(['Cytotoxic', 'NK', cells, not, only, directly, kill, tumor, cells, without, previous, stimulation, by, cytotoxic, effector, 'molecules,', such, as, perforin, and, granzymes, or, via, death, receptor, 'interactions,', but, also]), verbo([act]), complemento([as, regulatory, cells, for, the, immune, system, by, secreting, cytokines, and, chemokines])]). relacion([sujeto(['The', aim, of, this, review, is, to, highlight, therapeutic, strategies, utilizing, autologous, and, allogenic, 'NK', 'cells,', combinations, of, 'NK', cells, with, monoclonal, antibodies, to]), verbo([induce]), complemento(['antibody-dependent', cellular, 'cytotoxicity,', or, immune, checkpoint, inhibitors])]). relacion([sujeto(['Superior', and, inferior, clival, 'lines,', supracondylar, 'groove,', hypoglossal, 'canal,', arch, of, atlas, and, body, of, 'axis,', and, occipitocervical, joint]), verbo([act]), complemento([as, useful, bony, landmarks, whereas, longus, capitis, and, rectus, capitis, anterior, are, related, muscles, to, this, approach])]). relacion([sujeto(['Clinical', neuroscience]), verbo([has]), complemento([made, tremendous, advances, over, the, last, century])]). relacion([sujeto(['Encouragingly,', the, patient, and, their, caregivers, are, now, increasingly, willing, to, be, actively]), verbo([involved]), complemento([in, making, decisions])]). relacion([sujeto(['A', society, that, is, orienting, itself, toward, &, 'quot;rating"', and, &, 'quot;feedback"']), verbo([has]), complemento([made, this, 'doctor-patient', 'relationship,', a, 'consumer-service', provider, relationship])]). relacion([sujeto(['Moreover,', a, rapid, influx, of, information, from, potential, erroneous, sources, such, as, the, 'Internet']), verbo([has]), complemento([also, made, patient, and, caregivers, not, being, hesitant, to, taking, legal, course, in, the, case, of, adverse, events, during, treatment, or, simply, because, of, dissatisfaction])]). relacion([sujeto(['However,', it, is, not, clearly, established, if, monetary, benefits, acquired]), verbo([lead]), complemento([to, better, opportunities, for, recovery, of, the, patient])]). relacion([sujeto(['The', consumer, protection]), verbo([act]), complemento([and, commercialization, of, medical, services, may, well, have, an, adverse, effect, on, the, doctor, and, patient, relationship])]). relacion([sujeto(['The', 'Tamil', 'Nadu', model, of, public, health, is, renowned, for, its, success, in]), verbo([providing]), complemento([quality, health, services, at, an, affordable, cost, especially, to, the, rural, people])]). relacion([sujeto(['Tamil', 'Nadu']), verbo([has]), complemento([gained, significant, ground, in, the, various, aspects, of, health, in, the, last, few, decades, largely, because, of, the, significant, reforms, in, its, health, sector, which, dates, back, to, 1980, s, which, saw, rigorous, expansion, of, rural, health, infrastructure, in, the, state, besides, deployment, of, thousands, of, multipurpose, health, workers, as, village, health, nurses, in, rural, areas])]). relacion([sujeto(['Effective', implementation, of, 'Universal', 'Immunization', 'Programme,', formation, of, 'Tamil', 'Nadu', 'Medical', 'Services', 'Corporation', for]), verbo([regulating]), complemento([the, drug, procurement, and, promoting, generic, 'drugs,', early, incorporation, of, indigenous, system, of, medicine, into, health, care, 'service,', formulation, of, a, health, policy, in, 2003, by, the, state, with, special, emphasis, on, 'low-income,', disadvantaged, communities, alongside, efficient, implementation, of, 'The', 'Tamil', 'Nadu', 'Health', 'Systems', 'Project', '(', 'TNHSP)', are, the, major, factors, which, contributed, for, the, success, of, the, state])]). relacion([sujeto(['The', importance, of, good, political, commitment, and, leadership, in, the, health]), verbo([gains]), complemento([of, the, state, warrants, special, mention])]). relacion([sujeto(['Moreover,', the, economic, growth, of, the, 'state,', improved, literacy, 'rate,', gender, 'equality,', and, lowered, fertility, rate, in, the, last, few, decades, and, contributions, from, the, private, sector]), verbo([have]), complemento([their, share, in, the, public, health, success, of, the, state])]). relacion([sujeto(['Carcinogenesis']), verbo([caused]), complemento([by, human, papillomavirus, '(', 'HPV)', leads, to, 'over-expression', of, p16, protein])]). relacion([sujeto([p16, may]), verbo([act]), complemento([as, a, marker, of, 'HPV', integration, with, host, genome, and, serve, as, a, surrogate, marker, of, 'HPV', oncogenesis])]). relacion([sujeto([p16, immunostaining, with, greater, specificity, for, 'high-grade', lesions, may, improve, the, diagnostic, 'accuracy,', especially, for, 'high-grade', lesions, which]), verbo([have]), complemento([a, high, risk, of, progression, to, malignancy, and, thereby, necessitate, treatment])]). relacion([sujeto(['Molecular', assemblies, of, 'C18AA', exhibit, distinctive, thermal, 'responsiveness;', 'namely,', 'C18AA', can, form, a, gel, with, apolar, organic, 'solvents,', while, 'O/W', emulsions, of, 'C18AA']), verbo([act]), complemento([as, a, 'heat-induced', gelator, that, undergoes, a, phase, transition, from, solution, to, gel, upon, heating])]). relacion([sujeto(['Given', the, significant, time, and, financial, costs, of, developing, a, commercial, 'drug,', it, remains, important, to, constantly, reform, the, drug, discovery, pipeline, with, novel, technologies, that, can, narrow, the, candidates, down, to, the, most, promising]), verbo([lead]), complemento([compounds, for, clinical, testing])]). relacion([sujeto(['The', past, decade]), verbo([has]), complemento([witnessed, tremendous, growth, in, computational, capabilities, that, enable, in, silico, approaches, to, expedite, drug, discovery, processes])]). relacion([sujeto(['Molecular', dynamics, '(', 'MD)']), verbo([has]), complemento([become, a, particularly, important, tool, in, drug, design, and, discovery])]). relacion([sujeto(['In', the, present, 'study,', we]), verbo([have]), complemento([screened, for, nutraceuticals, '(', 'n=30)', that, would, act, at, low, micromolar, range, against, phenotypically, distinct, breast, cancer, cell, 'lines,', namely, 'MCF-7', '(', 'ER(+),', 'PR(+/-),', 'HER2(-)),', 'MDA-MB-231', '(', 'ER(-),', 'PR(-),', 'HER2(-))', and, 'SK-BR-3', '(', 'ER(-),', 'PR(-),', 'HER2(+)),', and, 'diosmin,', a, citrus, fruit, flavonoid, belonging, to, a, flavone, 'subclass,', was, selected])]). relacion([sujeto(['MCF-7', cell, line, was]), verbo([found]), complemento([to, be, the, most, sensitive, to, diosmin, treatment])]). relacion([sujeto(['Diosmin']), verbo([caused]), complemento(['G2/M', cell, cycle, 'arrest,', elevation, in, 'p53,', p21, and, p27, levels, and, 'stress-induced', premature, senescence, when, used, at, lower, concentrations, '(', 5, and, 10, 'μM)'])]). relacion([sujeto(['Diosmin', '(', 20, 'μM)', also]), verbo([promoted]), complemento([apoptosis, that, was, not, observed, in, normal, human, mammary, epithelial, cells, '(', 'HMEC)'])]). relacion([sujeto(['Diosmin']), verbo([stimulated]), complemento([oxidative, and, nitrosative, 'stress,', 'DNA', damage, and, changes, in, global, 'DNA', methylation, patterns])]). relacion([sujeto(['The', status, of, p53, '(', wild, type, versus, 'mutant)', and, the, levels, of]), verbo([phosphorylated]), complemento(['ERK1/2', in, a, steady, 'state,', and, 'diosmin-induced', autophagy, may, reflect, diverse, response, to, diosmin, treatment, in, 'MCF-7,', 'MDA-MB-231', and, 'SK-BR-3', 'cells,', which, in, turn, results, in, different, cell, fates])]). relacion([sujeto(['Taken', 'together,', diosmin, that]), verbo([acts]), complemento([at, low, micromolar, range, against, breast, cancer, cells, may, be, considered, as, a, promising, candidate, for, anticancer, therapy])]). relacion([sujeto(['Interestingly,', this, severe, evolutionary, constraint, among, other, things, demands, 'DNA', repair, systems, to, discriminate, between]), verbo([regular]), complemento([and, modified, bases])]). relacion([sujeto(['DNA', glycosylases, specifically]), verbo([recognize]), complemento([and, excise, damaged, bases, among, vast, majority, of, regular, bases, in, the, base, excision, repair, '(', 'BER)', pathway])]). relacion([sujeto(['To', counteract, these, mutagenic, threats, to, genome, 'stability,', cells, evolved, special, 'DNA', repair, systems, that]), verbo([target]), complemento([the, 'non-damaged', 'DNA', strand, in, a, duplex, to, remove, mismatched, regular, 'DNA', bases])]). relacion([sujeto(['Mismatch-specific', 'adenine-', and, 'thymine-DNA', glycosylases, '(', 'MutY/MUTYH', and, 'TDG/MBD4,', 'respectively)', initiated, 'BER', and, mismatch, repair, '(', 'MMR)', pathways, can]), verbo([recognize]), complemento([and, remove, normal, 'DNA', bases, in, mismatched, 'DNA', duplexes])]). relacion([sujeto(['Importantly,', in, 'DNA', repair, deficient, cells, bacterial, 'MutY,', human, 'TDG', and, mammalian, 'MMR', can]), verbo([act]), complemento([in, the, aberrant, 'manner:', 'MutY', and, 'TDG', removes, adenine, and, thymine, opposite, misincorporated, 8, -, oxoguanine, and, damaged, 'adenine,', 'respectively,', whereas, 'MMR', removes, thymine, opposite, to, 'O(6)-methylguanine'])]). relacion([sujeto(['These', unusual, activities]), verbo([lead]), complemento([either, to, mutations, or, futile, 'DNA', 'repair,', thus, indicating, that, the, 'DNA', repair, pathways, which, target, 'non-damaged', 'DNA', strand, can, act, in, aberrant, manner, and, introduce, genome, instability, in, the, presence, of, unrepaired, 'DNA', lesions])]). relacion([sujeto(['For', 'example,', the, aberrant, 'BER', and, 'MMR', pathways, for, oxidized, guanine, residues, can]), verbo([lead]), complemento([to, trinucleotide, expansion, that, underlies, 'Huntington\'s', 'disease,', a, severe, hereditary, neurodegenerative, syndrome])]). relacion([sujeto(['During', hypocotyl, 'photomorphogenesis,', light, signals, are, sensed, by, multiple, 'photoreceptors,', among, which, the, 'red/far-red', 'light-sensing', phytochromes]), verbo([have]), complemento([been, extensively, studied])]). relacion([sujeto(['However,', it, is, not, fully, understood, how, the, phytochromes]), verbo([modulate]), complemento([hypocotyl, growth])]). relacion([sujeto(['Here,', we, demonstrated, that, 'HIGH', 'EXPRESSION', 'OF', 'OSMOTICALLY', 'RESPONSIVE', 'GENES', 1, '(', 'HOS1),', which, is, known, to, either]), verbo([act]), complemento([as, 'E3', ubiquitin, ligase, or, affect, chromatin, 'organization,', inhibits, the, transcriptional, activation, activity, of, 'PHYTOCHROME', 'INTERACTING', 'FACTOR', 4, '(', 'PIF4)', that, promotes, hypocotyl, growth])]). relacion([sujeto(['Notably,', phyB]), verbo([induces]), complemento(['HOS1', activity, in, inhibiting, 'PIF4', function])]). relacion([sujeto(['These', observations]), verbo([provide]), complemento([a, molecular, basis, for, the, 'phyB-mediated', suppression, of, hypocotyl, growth, in, 'Arabidopsis'])]). relacion([sujeto(['Pre-clinical', models]), verbo([have]), complemento([also, lent, mechanistic, insights, into, the, biochemical, and, molecular, pathways, by, which, adequate, folate, exposure, conveys, these, protective, 'effects,', although, human, studies, are, beginning, to, establish, the, relevance, of, our, mechanistic, understanding, to, human, cancer, biology])]). relacion([sujeto(['To', 'date,', the, 'Wnt', signaling, cascade]), verbo([has]), complemento([been, the, pathway, most, examined, in, this, regard])]). relacion([sujeto(['The', relationship, between, folate, exposure, and, colorectal, cancer, risk, is, a, complex, 'one,', in, part, because, a, number, of, extrinsic, and, intrinsic, factors]), verbo([act]), complemento([as, effect, modifiers])]). relacion([sujeto(['This', review, discusses, how, the, intake, of, the, other, three, 'B-vitamins', integral, to, the, 1, -, carbon, pathway]), verbo([acts]), complemento([as, one, such, effect, modifier])]). relacion([sujeto(['In', 'addition,', two, concepts, that, remain, matters, of, considerable, debate, are, whether, parental, intake, of, folate, impacts, on, subsequent, cancer, risk, in, the, 'offspring,', and, whether, excessive, intakes, of, folate, may]), verbo([have]), complemento([a, paradoxical, 'cancer-promoting', 'effect:', observations, underlying, these, two, concepts, are, presented, as, well])]). relacion([sujeto(['A', significant, portion, of, the, key, biological, functions, of, αKlotho, '(', 'αKL)', and, its, cognate, ligand, 'Fibroblast', growth, 'factor-23', '(', 'FGF23)']), verbo([have]), complemento([been, revealed, through, the, study, of, rare, diseases, of, mineral, metabolism])]). relacion([sujeto(['These', findings]), verbo([have]), complemento([far, reaching, implications, for, common, disorders, such, as, chronic, kidney, 'disease-mineral', bone, disorder, '(', 'CKD-MBD)'])]). relacion([sujeto(['αKL\'s', predominant, effect, on, mineral, homeostasis, is, through, its, actions, in, the, kidney, as, a, 'co-receptor', for, 'FGF23,', however, emerging, data]), verbo([has]), complemento([shed, light, on, its, capacity, to, act, as, a, circulating, factor, through, the, cleavage, of, the, transmembrane, form, of, αKL, '(', '\'', 'mKL\')', to, produce, '\'', cleaved, 'KL\'', or, '\'', 'cKL\''])]). relacion([sujeto(['A', statistically, significant, temperature, warming, '(', 0.21, °, 'C', 'decade(-1)', for, mean, annual, 'temperature)']), verbo([has]), complemento([been, detected, in, the, 'region,', and, it, caused, a, reduction, of, the, glacierized, area, since, 1975, from, 3.5, to, 1.4, 'km(-2)'])]). relacion([sujeto(['New', small, lakes, formed, in, the, deglaciated, 'areas,']), verbo([increasing]), complemento([the, flooded, area, from1])]). relacion([sujeto([8]), verbo([ha]), complemento([in, 1976, to, 2.8, ha, in, 2014])]). relacion([sujeto(['Sediment', cores, revealed, a, high, sedimentation, rate, '(', &, 'gt;1cmyr(-1))', and, two, contrasted, 'facies,']), verbo([suggesting]), complemento([a, shift, toward, a, reduction, of, meltwater, inputs, and, higher, hydrological, variability, likely, due, to, an, increasing, role, of, precipitation, on, runoff, during, the, last, decades])]). relacion([sujeto(['With', this, hydrological, -, paleolimnological, approach, we]), verbo([have]), complemento([documented, the, association, between, recent, climate, variability, and, glacier, recession, and, the, rapid, transfer, of, hydroclimate, signal, to, depositional, and, geochemical, processes, in, high, elevation, 'Andean', environments])]). relacion([sujeto(['This,', study, also, alerts, about, water, quality, risks, as, proglacial, lakes]), verbo([act]), complemento([as, secondary, reservoirs, that, trap, trace, and, minor, elements, in, high, altitude, basins])]). relacion([sujeto(['Electron', microprobe, and, 'As', 'K-edge', 'X-ray', absorption, 'near-edge', spectroscopic, analyses, showed, the, 'As', is, predominantly]), verbo([associated]), complemento([with, primary, pyrites, in, both, source, and, freshly, blasted, waste, rock])]). relacion([sujeto(['However,', in, aged, waste, rock, the, 'As', is]), verbo([associated]), complemento([with, both, primary, pyrites, and, secondary, 'Fe', oxyhydroxides])]). relacion([sujeto(['Acid']), verbo([released]), complemento([from, pyrite, oxidation, to, 'Fe', oxyhydroxides, is, neutralized, by, carbonate, mineral, dissolution, that, buffers, the, pH, in, the, waste, rock, to, circumneutral, values])]). relacion([sujeto(['Adsorption', of, 'As', onto, secondary, 'Fe', oxyhydroxides]), verbo([provides]), complemento([an, internal, geochemical, control, on, 'As', release, during, pyrite, oxidation, and, porewater, flushing, from, the, 'dump,', resulting, in, the, low, 'As', concentrations, observed, in, porewater, '(', 'median:', 9.91, 'μg/L)', and, 'rock-drain', effluent, '(', 'median:', 0.31, 'μg/L)'])]). relacion([sujeto(['Secondary', 'Fe', oxyhydroxides]), verbo([act]), complemento([as, a, 'long-term', sink, for, 'As', under, present, day, hydrologic, settings, in, waste, rock, dumps, in, the, 'Elk', 'Valley'])]). relacion([sujeto(['The', functions, of, antimicrobial, peptides, in, skin, diseases, include, the, ability, to]), verbo([act]), complemento([as, cytokines, or, growth, 'factors,', driving, disorders, such, as, psoriasis, and, 'rosacea,', as, well, as, their, action, as, natural, antibiotics, to, control, bacteria, that, influence, diseases, such, as, atopic, dermatitis, and, acne])]). relacion([sujeto(['As', with, other, &, 'quot;isms,"', such, as, racism, and, 'sexism,', ageism]), verbo([leads]), complemento([to, bigotry, and, 'discrimination,', though, it, is, a, very, distinct, beast, in, 'that,', for, the, most, 'part,', other, &, 'quot;isms"', refer, to, those, different, from, 'ourselves:', 'distinct,', mutually, 'exclusive,', and, impervious, groups])]). relacion([sujeto(['Conversely,', age, is, a, fluid, social, construct, in, which, we, are, all, intimately]), verbo([bound]), complemento([as, we, move, through, the, 'lifespan,', transitioning, in, and, out, of, different, 'age-groups'])]). relacion([sujeto(['Periprosthetic', osteolysis]), verbo([induced]), complemento([by, wear, particles, can, lead, to, aseptic, 'loosening,', one, main, reason, of, arthroplasty, failure])]). relacion([sujeto(['However,', the, role, of, 'microRNA-130b', '(', 'miR-130b)', in, 'particle-induced', osteolysis, '(', 'PIO)']), verbo([has]), complemento([not, been, explored, yet])]). relacion([sujeto(['Real', time, 'PCR', and, western, blotting, were, performed, to, determine, the, expression, levels, of, 'miR-130b', and, 'frizzled-related', protein, '(', 'FRZB),', one, potential]), verbo([target]), complemento([of, 'miR-130b'])]). relacion([sujeto(['Results', showed, upregulated, 'miR-130b', and, downregulated, 'FRZB', in, both, 'PIO', mice, with, remarkable, osteolysis, and, 'particle-treated', 'MC3T3-E1', cells, showing]), verbo([inhibited]), complemento([proliferation, and, differentiation, assayed, by, bromodeoxy, urodine, '(', 'BrdU)', incorporation, and, alkaline, phosphatase, '(', 'ALP)', activity, respectively])]). relacion([sujeto(['Functional', studies, were, conducted, by, transfection, of, 'miR-130b', inhibitor, in, vitro, or, the, injections, of, 'miR-130b', inhibitor, or, small, interfering, 'RNA', '(', 'siRNA)']), verbo([targeting]), complemento(['FRZB', in, vivo])]). relacion([sujeto(['Luciferase']), verbo([report]), complemento([assays, demonstrated, that, 'miR-130b', indeed, negatively, regulated, 'FRZB', expression, by, 'targeting,', while, 'FRZB', could, reverse, the, opposed, effect, of, 'miR-130b', silence, on, 'PIO', development])]). relacion([sujeto(['Therefore,', the, upregulated, 'miR-130b', in, 'PIO', models, could]), verbo([act]), complemento([as, one, key, regulator, of, 'PIO', 'development,', partly, due, to, its, negative, regulation, on, 'FRZB'])]). relacion([sujeto(['The', 'Ebf2', 'gene,', belonging, to, the, 'Ebf', family, of, transcription, factors]), verbo([regulating]), complemento([cell, development, and, 'differentiation,', is, expressed, in, 'Schwann', 'cells,', and, 'Ebf2', knockout, mice, show, peripheral, nerve, defects])]). relacion([sujeto(['We', also]), verbo([found]), complemento([that, 'Ebf1', is, expressed, in, 'Schwann', cells])]). relacion([sujeto(['Combined', downregulation, of, 'Ebf', genes]), verbo([leads]), complemento([to, a, severe, impairment, of, myelin, formation, that, is, completely, rescued, by, their, specific, 'overexpression,', suggesting, that, the, expression, level, of, 'Ebf', genes, strongly, influences, axon, myelination])]). relacion([sujeto(['In', 'addition,', by, profiling, 'Ebf']), verbo([target]), complemento(['genes,', we, found, several, transcripts, belonging, to, pathways, actively, involved, in, peripheral, 'myelination,', including, 'Gliomedin,', a, gene, with, a, role, in, the, formation, of, the, nodes, of, 'Ranvier', and, recently, implicated, in, the, pathogenesis, of, the, 'nodo-paranodopathies'])]). relacion([sujeto(['Our', results]), verbo([suggest]), complemento([that, 'Ebf', genes, act, as, positive, regulators, of, myelination, and, directly, regulate, the, promoter, of, 'Gliomedin'])]). relacion([sujeto(['The', central, nervous, system, '(', 'CNS)', is, a, large, network, of, intercommunicating, cells, that, function, to]), verbo([maintain]), complemento([tissue, health, and, homeostasis])]). relacion([sujeto(['Considerable', evidence]), verbo([suggests]), complemento([that, glucocorticoids, exert, both, neuroprotective, and, neurodegenerative, effects, on, the, 'CNS'])]). relacion([sujeto(['Glucocorticoids']), verbo([act]), complemento([by, binding, two, related, receptors, in, the, 'cytoplasm,', the, mineralocorticoid, receptor, '(', 'MR)', and, the, glucocorticoid, receptor, '(', 'GR)'])]). relacion([sujeto(['The', glucocorticoid, receptor, complex]), verbo([mediates]), complemento([cellular, responses, by, transactivating, target, genes, and, by, 'protein:', protein, interactions])]). relacion([sujeto(['The', paradoxical, effects, of, glucocorticoids, on, neuronal, survival, and, death]), verbo([have]), complemento([been, attributed, to, the, concentration, and, the, ratio, of, mineralocorticoid, to, glucocorticoid, receptor, activation])]). relacion([sujeto(['Constitutively,']), verbo([expressed]), complemento([in, many, tissues, including, 'brain,', 'GILZ', mediates, many, of, the, actions, of, glucocorticoids])]). relacion([sujeto(['Recent', experimental, data, on, the, effects, of, 'GILZ', following]), verbo([induced]), complemento([stress, or, trauma, suggest, potential, roles, in, 'CNS', diseases])]). relacion([sujeto(['Here,', we]), verbo([provide]), complemento([a, short, overview, of, the, role, of, 'GILZ', in, 'CNS', health, and, discuss, three, potential, rationales, for, the, role, of, 'GILZ', in, 'Alzheimer\'s', disease, pathogenesis])]). relacion([sujeto(['Many', donors, and, recipients]), verbo([report]), complemento([an, improved, relationship, after, 'transplantation;', 'however,', 'tension,', 'neglect,', 'guilt,', and, proprietorial, concern, over, the, recipient, can, impede, donor, and, recipient, 'well-being', and, outcomes])]). relacion([sujeto(['From', 40, studies]), verbo([involving]), complemento([1, ',', 440, participants, '(', 889, donors, and, 551, 'recipients)', from, 13, 'countries,', we, identified, 6, themes])]). relacion([sujeto([&, 'quot;Desiring', 'attention"', was]), verbo([expressed]), complemento([by, donors, who, wanted, recognition, for, the, act, of, donation, and, were, envious, and, resentful, of, the, attention, the, recipient, received])]). relacion([sujeto([&, 'quot;Retaining', kidney, 'ownership"', reflected, the, 'donor\'s', inclination, to]), verbo([ensure]), complemento([that, the, recipient, protected, &, 'quot;their"', kidney])]). relacion([sujeto([&, 'quot;Enhancing', social, 'participation"', encompassed, relieving, both, the, caregiver, from, the, constraints, of, dialysis, and, the, recipient, from]), verbo([increased]), complemento([involvement, and, contribution, in, family, life])]). relacion([sujeto(['Living', kidney, donation, can, strengthen, 'donor-recipient', relationships, but, may]), verbo([trigger]), complemento([or, exacerbate, unresolved, 'angst,', 'tension,', 'jealousy,', and, resentment])]). relacion([sujeto(['The', causative, agent, of, 'toxoplasmosis,', the, intracellular, parasite, 'Toxoplasma', 'gondii,', delivers, a, 'protein,', 'GRA24,', into, the, cells, it, infects, that]), verbo([interacts]), complemento([with, the, 'mitogen-activated', protein, '(', 'MAP)', kinase, p38α, '(', 'MAPK14),', leading, to, activation, and, nuclear, translocation, of, the, host, kinase, and, a, subsequent, inflammatory, response, that, controls, the, progress, of, the, parasite])]). relacion([sujeto(['The', purification, of, a, recombinant, complex, of, 'GRA24', and, human, p38α]), verbo([has]), complemento([allowed, the, molecular, basis, of, this, activation, to, be, determined])]). relacion([sujeto(['GRA24', is, shown, to, be, intrinsically, 'disordered,']), verbo([binding]), complemento([two, kinases, that, act, 'independently,', and, is, the, only, factor, required, to, bypass, the, canonical, 'mitogen-activated', protein, kinase, activation, pathway])]). relacion([sujeto(['In', 'addition,', the, recombinant, complex, forms, a, powerful, 'in vitro', tool, to, evaluate, the, specificity, and, effectiveness, of, p38α, inhibitors, that]), verbo([have]), complemento([advanced, to, clinical, 'trials,', as, it, provides, a, hitherto, unavailable, stable, and, highly, active, form, of, p38α])]). relacion([sujeto(['Entomophagy']), verbo([has]), complemento([been, linked, to, 'nutritional,', 'economic,', social, and, ecological, benefits])]). relacion([sujeto(['Furthermore,', the, presence, of, several, 'gut-associated', 'bacteria,', some, of, which, may]), verbo([act]), complemento([as, opportunistic, pathogens, in, 'humans,', were, found, through, pyrosequencing])]). relacion([sujeto([in, mealworm, 'larvae,', which]), verbo([has]), complemento([been, found, to, be, related, to, neurodegenerative, diseases, in, animals, and, humans])]). relacion([sujeto(['(', with, low, 'abundance)', was, also]), verbo([found]), complemento([through, pyrosequencing])]). relacion([sujeto(['The', results, of, this, study, contribute, to, the, elucidation, of, the, microbiota]), verbo([associated]), complemento([with, edible, insects, and, encourage, further, studies, aimed, to, evaluate, the, influence, of, rearing, and, processing, conditions, on, that, microbiota])]). relacion([sujeto(['Sixteen', workers, were, individually, interviewed, and, eight, additional, workers]), verbo([participated]), complemento([in, two, focus, groups])]). relacion([sujeto(['Social', integration, should, be, a]), verbo([targeted]), complemento([focus, of, service, by, structurally, embedding, a, social, integration, specialist, onto, the, 'ACT', model])]). relacion([sujeto([',', does, the, child]), verbo([have]), complemento([the, relevant, structures, for, passive, 'sentences?)', or, access, this, knowledge, during, communication, '(', e])]). relacion([sujeto(['After', sentence, 'presentation,']), verbo([decreased]), complemento([sensitivity, generated, interpretive, challenges, and, average, 'SES-related', differences, for, passives, requiring, syntactic, revision, '(', &, 'quot;The', seal, is, quickly, eaten, by, 'it")'])]). relacion([sujeto(['Critically,', no, differences, were]), verbo([found]), complemento([when, revision, was, not, needed, '(', &, 'quot;It', is, quickly, eaten, by, the, 'seal")'])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, all, children, shared, an, ability, to, acquire, 'passives,', but, 'SES-related', differences, in, 'real-time', processing, can, impact, the, accuracy, of, utterance, interpretation])]). relacion([sujeto(['The', sterile, insect, technique]), verbo([has]), complemento([been, advocated, as, a, 'non-chemical', alternative, to, currently, available, control, methods])]). relacion([sujeto(['In', 'area-wide', sterile, insect]), verbo([release]), complemento(['programs,', males, act, as, true, vectors, of, sterility])]). relacion([sujeto(['The', aim, of, this, research, was, to, develop, a, mechanical, sexing, system, based, on, pupal, size, to]), verbo([decrease]), complemento([the, proportion, of, 'ASL', females])]). relacion([sujeto(['Pupal', sexual, dimorphisms, identified, in, this, research, can, be, used, to, design, a, sieve, to, aid, in, reducing, the, proportion, of, females, prior, to, irradiation, thus, improving, the, efficacy, of, an, 'area-wide', sterile, insect]), verbo([release]), complemento([program])]). relacion([sujeto(['We', describe, the, scope, of, health, care]), verbo([required]), complemento([for, all, living, kidney, donors, that, reflects, contemporary, understanding, of, 'long-term', donor, health, 'outcomes,', propose, an, approach, to, identify, donor, health, conditions, which, should, be, covered, within, the, framework, of, financial, 'neutrality,', and, propose, strategies, to, pay, for, this, care])]). relacion([sujeto(['Despite', the, 'Affordable', 'Care', 'Act', in, the, 'United', 'States,', donors, continue, to]), verbo([have]), complemento([inadequate, coverage, for, important, health, conditions, that, are, either, donation, related, or, may, compromise, 'post-donation', kidney, function])]). relacion([sujeto(['In', other, countries, lacking, health, insurance, for, all, 'residents,', sufficient, data, exist, to, allow, creation, of, a, compensation, fund, or, donor, insurance, policies, to]), verbo([ensure]), complemento([appropriate, care])]). relacion([sujeto(['Providing', coverage, for, 'donation-related', sequelae, as, well, as, care, to, preserve, 'post-donation', kidney, function]), verbo([ensures]), complemento([protection, against, the, financial, burdens, of, health, care, encountered, by, donors, throughout, their, lifetime])]). relacion([sujeto(['The', 'Affordable', 'Care', 'Act', '(', 'ACA)']), verbo([requires]), complemento([tobacco, cessation, as, a, preventive, service, with, no, patient, cost, share, for, all, 'FDA-approved', cessation, medications])]). relacion([sujeto(['Health', plans]), verbo([have]), complemento([a, vital, role, in, supporting, smoking, cessation, by, managing, medication, 'access,', but, uncertainty, remains, on, the, gaps, between, smoking, cessation, requirements, and, what, is, actually, occurring, in, practice])]). relacion([sujeto(['This', study, presents, current, cessation, 'patterns,', 'real-world', drug, costs, and, plan, benefit, design, 'data,', and, estimates, the, 1, -, to, 5, -, year, pharmacy, budget, impact, of]), verbo([providing]), complemento(['ACA-required', coverage, for, smoking, cessation, products, to, understand, the, fiscal, impact, to, a, 'US', healthcare, plan])]). relacion([sujeto(['The', projected, 'PMPM', cost, of]), verbo([providing]), complemento([coverage, for, smoking, cessation, medications, is, '$0'])]). relacion([sujeto(['Results', of, this, study, reinforce, that, the, impact, of, adopting, the, 'ACA', requirements, for, smoking, cessation, coverage, will]), verbo([have]), complemento([a, limited, 'near-term', impact, on, health, 'plan\'s', budgets])]). relacion([sujeto(['This', study, aimed, to]), verbo([find]), complemento([out, the, presence, of, carcinogenic, heavy, metals, in, gallstones, and, to, explore, the, aetiopathogenesis, of, gallbladder, 'pre-malignancy', and, malignancy])]). relacion([sujeto([1, ')', ',']), verbo([lead]), complemento(['(', 'p < 0'])]). relacion([sujeto(['\'', 'Dense', 'deposits\'', of, these, metals, in, the, gallstones, which, is, the, first, 'observation,', may]), verbo([act]), complemento([as, crucial, doses, of, carcinogens])]). relacion([sujeto(['Although', many, more, proteins, are]), verbo([involved]), complemento([in, the, formation, of, 'TJ', 'complexes,', claudins, are, the, only, 'TJ', proteins, that, are, able, to, form, 'TJ-like', strands, when, overexpressed, in, cells, that, are, normally, devoid, of, 'TJs', '(', e])]). relacion([sujeto(['Within', the, paracellular, 'cleft,', the, extracellular, domains, of, claudins]), verbo([provide]), complemento([the, matrix, that, seals, the, paracellular, pathway])]). relacion([sujeto(['However,', within, this, 'matrix,', some, claudins]), verbo([act]), complemento([as, channels, that, specifically, allow, certain, ions, to, cross, this, barrier])]). relacion([sujeto(['Recently,', long, 'non-coding', 'RNAs', '(', 'lncRNAs)']), verbo([have]), complemento([been, shown, to, have, critical, regulatory, roles, in, tumourigenesis])]). relacion([sujeto(['Increasing', evidence]), verbo([has]), complemento([suggested, that, lncRNA, 'NEAT1', has, been, implicated, in, various, types, of, human, cancer])]). relacion([sujeto(['Here,', we]), verbo([found]), complemento([that, the, expression, level, of, 'NEAT1', was, higher, in, 'PC', tissues, compared, to, the, corresponding, 'non-tumor', tissues])]). relacion([sujeto(['Furthermore,', we, also]), verbo([found]), complemento([that, knockdown, of, 'NEAT1', remarkably, suppressed, cell, proliferation, by, inducing, cell, cycle, arrest, and, apoptosis, promotion, in, 'PC', cells])]). relacion([sujeto(['Moreover,', bioinformatics, analysis, and, luciferase, reporter, assay, revealed, that, 'NEAT1', directly]), verbo([bound]), complemento([to, the, 'miR-506-3p,', which, has, been, reported, to, act, as, a, tumor, suppressor, in, diverse, cancers])]). relacion([sujeto(['Overall,', our, results]), verbo([suggested]), complemento([that, 'NEAT1', functions, as, an, oncogenic, lncRNA, in, 'PC,', which, could, be, a, novel, diagnostic, and, therapeutic, target, for, 'PC'])]). relacion([sujeto(['We']), verbo([have]), complemento([previously, shown, that, peptides, of, the, isolated, 'G', 'α-helix', '(', 'G-helix)', domain, of, maspin, show, bioactivity])]). relacion([sujeto(['Here', we]), verbo([report]), complemento([the, use, of, functional, assays, of, these, behaviours, to, investigate, whether, other, 'maspin-derived', peptides, impact, directly, on, 'VSMC;', focusing, on, potential, 'anti-atherogenic', properties])]). relacion([sujeto(['Of', the, novel, peptides, screened, those, with, the, sequences, of, maspin, strand, 4, and, 5, of, beta, sheet, 'B', '(', 'S4B', and, 'S5B)', reduced, 'VSMC', 'migration,', invasion, and, 'proliferation,', as, well, as]), verbo([increasing]), complemento([cell, adhesion])]). relacion([sujeto(['This', is, the, first, time, that, these, parts, of, maspin]), verbo([have]), complemento([been, highlighted, as, having, key, roles, affecting, cell, function])]). relacion([sujeto(['We', present, evidence, for, a, mechanism, whereby, 'S4B', and, 'S5B']), verbo([act]), complemento([through, 'ERK1/2', and, 'AMP-activated', protein, kinase, '(', 'AMPK)', to, influence, 'VSMC', responses])]). relacion([sujeto(['Corticotropin-releasing', factor, '(', 'CRF)', is, a, neurohormone]), verbo([released]), complemento([from, the, paraventricular, nucleus, of, the, hypothalamus, into, the, median, eminence, to, elicit, release, of, adrenocorticotrophin, from, the, anterior, pituitary])]). relacion([sujeto(['It', may]), verbo([act]), complemento([to, modulate, autonomic, function, and, behavior, in, concert, with, the, endocrine, effects])]). relacion([sujeto(['Conflicting', animal, studies, about, the, role, of, 'CRF', in, 'micturition,', either, facilitating, or, 'inhibiting,']), verbo([have]), complemento([been, raised])]). relacion([sujeto(['It', was]), verbo([suggested]), complemento([to, be, a, novel, target, for, treatment, of, urinary, disorders, based, on, the, finding, that, manipulation, of, 'CRF', in, the, pontine, micturition, circuit, could, affect, urodynamic, function])]). relacion([sujeto(['Twenty-nine', children, aged, 8, -, 14, years, complaining, of, primary, monosymptomatic, nocturnal, enuresis, and, 16, 'age-', and, 'sex-matched', healthy, children, with, good, toilet, control, day, and, night, were]), verbo([recruited]), complemento([to, the, study])]). relacion([sujeto(['Several', animal, studies]), verbo([suggested]), complemento([that, 'CRF', in, descending, projections, from, 'Barrington\'s', nucleus, to, the, lumbosacral, parasympathetic, neurons, is, inhibitory, to, 'micturition,', which, supports, our, results, and, the, assumption, that, reduction, of, the, evening, serum, 'CRF', level, could, have, a, role, in, the, occurrence, of, primary, monosymptomatic, nocturnal, enuresis])]). relacion([sujeto(['No', significant, difference, was]), verbo([found]), complemento([between, morning, and, evening, 'CRF', serum, levels, in, either, cases, or, 'controls,', which, negates, our, assumption, of, having, a, rhythmic, pattern, of, release, '(', 'figure)'])]). relacion([sujeto(['Deep', sleep, and, difficult, arousal, were]), verbo([found]), complemento([to, have, a, major, role, in, primary, monosymptomatic, nocturnal, enuresis])]). relacion([sujeto(['CRF', was, deficient, in, our, enuretic, 'children,', which, may, draw, attention, to, the, possible, pathophysiological, implications, in, primary, nocturnal, enuresis, '(', either, at, the, level, of]), verbo([loss]), complemento([of, inhibitory, effect, on, micturition, or, lack, of, arousal, in, response, to, bladder, 'distension)'])]). relacion([sujeto(['The', purpose, of, this, study, was, to, evaluate, adherence, to, the, 3, recommendations, most, strongly]), verbo([associated]), complemento([with, health, outcomes, in, new, 24, -, h, movement, guidelines, and, their, relationship, with, adiposity, '(', obesity, and, body, mass, index, 'z-score)', across, countries, participating, in, the, 'International', 'Study', of, 'Childhood', 'Obesity,', 'Lifestyle', and, the, 'Environment', '(', 'ISCOLE)'])]). relacion([sujeto(['Compared', to, not, meeting, the, 24, -, h, movement, recommendations, either, independently, or, 'combined,', meeting, them, was, significantly]), verbo([associated]), complemento([with, a, lower, 'BMI', 'z-score'])]). relacion([sujeto(['Future', efforts, should, aim, to]), verbo([find]), complemento([promising, ways, to, increase, daily, physical, 'activity,', reduce, screen, 'time,', and, ensure, an, adequate, 'night\'s', sleep, in, children])]). relacion([sujeto(['The', spread, of, 'Plasmodium', falciparum, resistance, to, artemisinin, derivatives, in, 'Southeast', 'Asia', is, a, major, source, of, concern, and, the, emergence, of, resistance, in, 'Africa', would]), verbo([have]), complemento([dramatic, 'consequences,', by, increasing, malaria, mortality, and, morbidity])]). relacion([sujeto(['It', is, therefore, urgent, to, implement]), verbo([regular]), complemento([monitoring, in, sentinel, sites, in, 'sub-Saharan', 'Africa', using, robust, and, 'easy-to-implement', tools])]). relacion([sujeto(['Only', synonymous, mutations, were]), verbo([found]), complemento([with, a, low, prevalence, '(', 4.3, '%', ')'])]). relacion([sujeto(['It']), verbo([has]), complemento([special, global, significance, for, its, record, of, early, pelagic, fishing, and, ancient, shell, fish, hooks])]). relacion([sujeto(['Third,', the, 'Jerimalai', assemblage, bears, a, striking, resemblance, to, the, assemblage, from, 'Liang', 'Bua,', argued, by, the, 'Liang', 'Bua', excavation, team, to, be]), verbo([associated]), complemento([with, 'Homo', floresiensis])]). relacion([sujeto(['Degradation', pathway, and, surface, biosorption, of, triphenyltin, '(', 'TPT)', by, effective, microbes]), verbo([have]), complemento([been, investigated, in, the, past])]). relacion([sujeto(['However,', unclear, interactions, among, membrane, components, and, 'TPT']), verbo([binding]), complemento([and, transport, are, still, obstacles, to, understanding, 'TPT', biotransformation])]). relacion([sujeto(['To']), verbo([reveal]), complemento([the, mechanism, 'involved,', the, phospholipid, 'expression,', membrane, 'potential,', cellular, mechanism, and, molecular, dynamics, between, 'TPT', and, fatty, acids, '(', 'FAs)', during, the, 'TPT', degradation, process, in, the, presence, of, 'd-malic', acid, '(', 'DMA)', were, studied])]). relacion([sujeto(['The', results, show, that, the, degradation, efficiency, of, 1, &, 'nbsp;mg L(-1)', 'TPT', by, 'Bacillus', thuringiensis, '(', 1, &, 'nbsp;g L(-1))', with, 0.5, or, 1, &, 'nbsp;mg L(-1)', 'DMA', reached, values, up, to, approximately, 90, '%', due, to, the, promotion, of, element, metabolism, and, cellular, 'activity,', and, the, depression, of, 'FA', synthesis]), verbo([induced]), complemento([by, 'DMA'])]). relacion([sujeto(['The', addition, of, 'DMA']), verbo([caused]), complemento([conversion, of, more, linoleic, acid, into, 10, -, 'oxo-12(Z)-octadecenoic', 'acid,', increased, the, membrane, 'permeability,', and, alleviated, the, decrease, in, membrane, 'potential,', resulting, in, 'TPT', transport, and, degradation])]). relacion([sujeto(['Fluorescence', analysis]), verbo([reveals]), complemento([that, the, endospore, of, 'B'])]). relacion([sujeto([thuringiensis, could]), verbo([act]), complemento([as, an, indicator, for, membrane, potential, and, cellular, activities])]). relacion([sujeto(['Metal', deposition, on, oxide, surfaces, usually, results, in, 'adatoms,', 'clusters,', or, islands, of, the, deposited, 'material,', where, defects, in, the, surface, often]), verbo([act]), complemento([as, nucleation, centers])]). relacion([sujeto(['Increasing', use, of, engineered, nanoparticles]), verbo([has]), complemento([led, to, extensive, research, into, their, potential, hazards, to, the, environment, and, human, health])]). relacion([sujeto(['Interestingly,', the, peritrophic, membrane, appeared, to]), verbo([act]), complemento([as, a, semipermeable, barrier, between, the, lumen, and, the, gut, 'epithelium,', permitting, only, single, particles, through])]). relacion([sujeto(['Importantly,', gold, nanoparticles, were, in, fact]), verbo([found]), complemento([inside, holocrine, cells, with, disrupted, membranes])]). relacion([sujeto(['Several', foods, on, the, 'market,', such, as, yogurt, and, fermented, 'milk,', include, mixtures, of, prebiotics, and, probiotic, microorganisms, effective, in]), verbo([promoting]), complemento([the, proliferation, and, equilibrium, of, intestinal, 'bacteria,', thus, improving, gut, health])]). relacion([sujeto(['Particularly,', researchers, and, the, public]), verbo([have]), complemento([shown, increasing, interest, in, the, combination, of, probiotics, with, natural, substances, that, promote, health, or, that, can, act, as, substrates, to, promote, bacterial, growth])]). relacion([sujeto(['In', addition, to, dopamine, neuron, 'firing,', cholinergic, interneurons, '(', 'ChIs)']), verbo([regulate]), complemento([dopamine, release, in, the, striatum, via, presynaptic, nicotinic, receptors, '(', 'nAChRs)', on, dopamine, axon, terminals])]). relacion([sujeto(['Synchronous', activity, of, 'ChIs', is, necessary, to, evoke, dopamine]), verbo([release]), complemento([through, this, pathway])]). relacion([sujeto(['The', 'frequency-dependence', of, disynaptic, nicotinic, modulation]), verbo([has]), complemento([led, to, the, hypothesis, that, nAChRs, act, as, a, 'high-pass', filter, in, the, dopaminergic, microcircuit])]). relacion([sujeto(['Here,', we, used, optogenetics, to, selectively]), verbo([stimulate]), complemento([either, 'ChIs', or, dopamine, terminals, directly, in, the, striatum])]). relacion([sujeto(['We']), verbo([found]), complemento([that, 'nicotinic-mediated', dopamine, release, was, blunted, at, higher, frequencies, because, nAChRs, exhibit, prolonged, desensitization, after, a, single, pulse, of, synchronous, 'ChI', activity])]). relacion([sujeto(['We', further, assessed, how, opioid, receptors]), verbo([modulate]), complemento([these, two, mechanisms, of, release])]). relacion([sujeto(['Bath', application, of, the, κ, opioid, receptor, agonist, 'U69593']), verbo([decreased]), complemento(['D2-receptor', activation, through, both, 'pathways,', whereas, the, μ, opioid, receptor, agonist, 'DAMGO', decreased, 'D2-receptor', activity, only, as, a, result, of, 'cholinergic-mediated', dopamine, release])]). relacion([sujeto(['Thus', the]), verbo([release]), complemento([of, dopamine, can, be, independently, modulated, when, driven, by, either, dopamine, neurons, or, cholinergic, interneurons])]). relacion([sujeto(['Geometric', 'Berry', phase, is]), verbo([associated]), complemento([with, these, spectral, degeneracies])]). relacion([sujeto(['The', fully, reconfigurable, geometry, of, the, potential, walls, controlled, by, the, optical, pump, enables, a, striking, experimental, visualization, of, the, 'Berry', phase]), verbo([associated]), complemento([with, the, diabolical, point])]). relacion([sujeto(['This']), verbo([has]), complemento([led, to, a, search, for, alternatives, to, maintain, quality])]). relacion([sujeto(['In', this, 'sense,', antioxidant, compounds]), verbo([have]), complemento([been, used, to, prevent, such, lipid, deterioration])]). relacion([sujeto(['Among', the, most, used, compounds, are, 'tocopherols,', 'which,', due, to, their, natural, 'origin,']), verbo([have]), complemento([become, an, excellent, alternative, to, prevent, or, retard, lipid, oxidation, and, maintain, the, quality, of, marine, products])]). relacion([sujeto(['Tocopherols', as, antioxidants]), verbo([have]), complemento([been, studied, both, exogenously, and, endogenously])]). relacion([sujeto(['It']), verbo([has]), complemento([been, observed, that, exogenous, tocopherols, incorporated, in, low, concentrations, maintain, the, quality, of, both, muscle, and, the, extracted, oils, during, food, storage])]). relacion([sujeto(['However,', it]), verbo([has]), complemento([been, reported, that, tocopherols, applied, at, higher, concentrations, act, as, a, prooxidant, 'molecule,', probably, because, their, reactions, with, singlet, oxygen, may, generate, free, radicals, and, cause, the, oxidation, of, polyunsaturated, fatty, acids, in, fish, oils])]). relacion([sujeto(['Increasing', evidence]), verbo([has]), complemento([demonstrated, a, significant, role, for, long, 'non-coding', 'RNAs', '(', 'lncRNAs)', in, tumorigenesis])]). relacion([sujeto(['S26)', was, constructed, to, determine, the, expression, profile, of, lncRNAs, using, the, microarray, 'analysis,', and, we]), verbo([found]), complemento([167, lncRNAs, and, 209, mRNAs, were, differentially, expressed])]). relacion([sujeto(['Bioinformatic', analysis, indicated, that, the, dysregulated, mRNAs]), verbo([participated]), complemento([in, important, biological, regulatory, functions, in, 'NPC'])]). relacion([sujeto(['Furthermore,', the, expression, level, of, 'ENST00000470135,', which, was, the, most, upregulated, lncRNA, in, high, metastatic, cell, 'lines,', was, significantly, higher, in, 'NPC', cell, lines, and, tissues, with, lymph, node, metastasis, '(', 'LNM)', and, knocking, down, 'ENST00000470135']), verbo([suppressed]), complemento([the, 'migration,', invasion, and, proliferation, of, 'NPC', cells, in, vitro])]). relacion([sujeto(['The', dysregulated, lncRNAs, may]), verbo([act]), complemento([as, novel, biomarkers, and, therapeutic, targets, for, 'NPC'])]). relacion([sujeto(['The', vast, amount, of, data, that, are, generated, and, exchanged, between, the, 'IoT', nodes]), verbo([require]), complemento([innovative, context, modeling, approaches, that, go, beyond, currently, used, models])]). relacion([sujeto(['Salivary', antibodies, may]), verbo([act]), complemento([as, 'non-invasive', marker, of, systemic, immunity, enabling, assessment, of, vaccination, and, protection, against, bacterial, infections])]). relacion([sujeto(['Median', 'IgG', and, 'IgA', pneumococcal, salivary, parameters, were, able, to, identify, individuals, who, had, protective, levels, in, serum, on, '≥', 8, /, 12, serotypes, with, moderate, 'accuracy:', median, 'IgA', secretion, rates]), verbo([provided]), complemento([the, best, sensitivity, '(', 73, '%', ')', and, specificity, '(', 71, '%', ')'])]). relacion([sujeto(['These', findings]), verbo([suggest]), complemento([that, 'IgG', and, 'IgA', pneumococcal, specific, antibodies, in, saliva, may, be, useful, surrogate, markers, of, antibody, status, in, serum])]). relacion([sujeto(['Bevacizumab', use, was, similar, in, both, arms, '(', 'IPT', '(', 64, '%', ')', versus, 'RPT', '(', 70, '%', ')', ')', ;, compared, with, chemotherapy, 'alone,', bevacizumab, use, was]), verbo([associated]), complemento([with, significantly, longer, 'PFS', '(', 'IPT:', 8.5, months, vs, 4.7, 'months,', 'P', =, 0.017, ;, 'RPT:', 10.8, months, vs, 5.8, 'months,', 'P', &, 'lt;', 0.001, ')', and, 'OS', '(', 'IPT:', 20, months, vs, 14.8, 'months,', 'P', =, 0.005, ;, 'RPT:', 24.4, months, vs, 17.3, 'months,', 'P', =, 0.004, ')', ')'])]). relacion([sujeto(['(', 1, ')', 'Bevacizumab', use, in, an, 'IPT', was]), verbo([associated]), complemento([with, more, 'GI', perforations, '(', 4.5, '%', vs, 1.8, '%', ',', 'P', =, 0.21, ')', but, less, frequent, bleeding, '(', 1.5, '%', vs, 5.3, '%', ',', 'P', =, 0.05, ')', and, thrombosis, '(', 1.5, '%', vs, 2.7, '%', ',', 'P', =, 0.47, ')', ',', versus, chemotherapy, alone])]). relacion([sujeto(['p53-Transcriptional-regulated', proteins]), verbo([interact]), complemento([with, a, large, number, of, other, signal, transduction, pathways, in, the, 'cell,', and, a, number, of, positive, and, negative, autoregulatory, feedback, loops, act, upon, the, p53, response])]). relacion([sujeto(['P53', directly, controls, the, 'POMC/α-MSH', productions]), verbo([induced]), complemento([by, ultraviolet, '(', 'UV)', and, is, associated, with, 'UV-independent', pathological, pigmentation])]). relacion([sujeto(['When', identifying, the, causative, gene, of, dyschromatosis, universalis, hereditaria, '(', 'DUH),', we]), verbo([found]), complemento([three, mutations, encoding, amino, acid, substitutions, in, the, gene, 'SAM', and, 'SH3', domain, containing, 1, '(', 'SASH1),', and, 'SASH1', was, associated, with, guanine, 'nucleotide-binding', protein, 'subunit-alpha', isoforms, short, '(', 'Gαs)'])]). relacion([sujeto(['We', demonstrate, that, 'SASH1', is, physiologically]), verbo([induced]), complemento([by, p53, upon, 'UV', stimulation, and, 'SASH', and, p53, is, reciprocally, induced, at, physiological, and, pathophysiological, conditions])]). relacion([sujeto(['SASH1', is]), verbo([regulated]), complemento([by, a, novel, 'p53/POMC/α-MSH/Gαs/SASH1', cascade, to, mediate, melanogenesis])]). relacion([sujeto(['A', novel, 'p53/POMC/Gαs/SASH1', autoregulatory, positive, feedback, loop, is]), verbo([regulated]), complemento([by, 'SASH1', mutations, to, induce, pathological, hyperpigmentation, phenotype])]). relacion([sujeto(['Our', study, demonstrates, that, a, novel, 'p53/POMC/Gαs/SASH1', autoregulatory, positive, feedback, loop, is]), verbo([regulated]), complemento([by, 'SASH1', mutations, to, induce, pathological, hyperpigmentation, phenotype])]). relacion([sujeto(['Even', species, within, the, same, assemblage]), verbo([have]), complemento([varied, responses, to, climate, 'change,', and, there, is, a, poor, understanding, for, why, some, taxa, are, more, sensitive, to, climate, than, others])]). relacion([sujeto(['To', test, how, marine, species]), verbo([respond]), complemento([to, climate, 'variability,', we, analyzed, 73, diverse, taxa, off, the, southeast, 'U'])]). relacion([sujeto(['We']), verbo([found]), complemento([that, winter, temperatures, were, particularly, useful, for, explaining, interannual, variation, in, 'species\'', distribution, and, 'biomass,', though, the, direction, and, magnitude, of, the, response, varied, among, species, from, strongly, 'negative,', to, little, 'response,', to, strongly, positive])]). relacion([sujeto(['Based', on, the, life, stages, of, the, species, 'surveyed,', winter, temperature, appears, to]), verbo([act]), complemento([through, overwinter, mortality, of, juveniles, or, as, a, cue, for, migration, timing])]). relacion([sujeto(['We', predict, that, this, assemblage, will, be, responsive, to, projected]), verbo([increases]), complemento([in, 'temperature,', and, that, winter, temperature, may, be, broadly, important, for, species, relationships, with, climate, on, a, global, scale])]). relacion([sujeto(['However,', recent, findings, with, 2, ',', 4, -, 'D', specific, mutants]), verbo([suggested]), complemento([that, 2, ',', 4, -, 'D', and, 'IAA', might, also, use, distinct, pathways, to, modulate, 'Arabidopsis', root, growth])]). relacion([sujeto(['The', ubiquitin, proteasome, 'mutants,', 'tir1-1', and, 'axr1-12,', which, show]), verbo([enhanced]), complemento([resistance, to, 2, ',', 4, -, 'D', compared, with, 'IAA', for, root, growth, 'inhibition,', were, also, found, to, have, less, disrupted, actin, filament, networks, after, 2, ',', 4, -, 'D', exposure])]). relacion([sujeto(['Roots', of, the, double, mutant, 'aar1-1', 'tir1-1', also, showed]), verbo([enhanced]), complemento([resistance, to, 2, ',', 4, -, 'D-induced', root, growth, inhibition, and, actin, degradation, compared, with, their, respective, parental, lines])]). relacion([sujeto(['Collectively,', these, results]), verbo([suggest]), complemento([that, the, effects, of, 2, ',', 4, -, 'D', on, actin, filament, organization, and, root, growth, is, mediated, through, synergistic, interactions, between, 'SMAP1', and, 'SCF(TIR)(1)', ubiquitin, proteasome, components])]). relacion([sujeto(['The', higher, expression, of, 'VEGF,', 'EGFR', and, 'c-jun', in, early, pregnancy, was, observed, to, be, independent, of, 'DNA', methylation, while, it, was]), verbo([associated]), complemento([with, 'H3', 'K9/K27', trimethylations])]). relacion([sujeto(['Also,', abnormally, higher, expression, of, 'c-jun', in, 'GTDs', was]), verbo([associated]), complemento([with, lower, 'H3K9me3', level, at, its, promoter])]). relacion([sujeto(['Importantly,', our, promoter, methylation, data, indicated, that, 'VEGF', may]), verbo([act]), complemento([as, novel, fetal, 'DNA', diagnostic, marker, for, preeclampsia, and, molar, pregnancies, in, maternal, plasma])]). relacion([sujeto(['Glutaminases', may]), verbo([act]), complemento([as, multifunctional, proteins, able, to, perform, different, 'tasks:', the, discovery, of, multiple, transcript, variants, in, neurons, and, glial, 'cells,', novel, extramitochondrial, 'localizations,', and, 'isoform-specific', proteininteracting, partners, strongly, support, possible, moonlighting, functions, for, these, proteins])]). relacion([sujeto(['The', 'Affordable', 'Care', 'Act', '(', 'ACA)']), verbo([has]), complemento([expanded, health, coverage, for, thousands, of, 'Illinois', residents])]). relacion([sujeto(['High', rates, of, undetected, diabetic, retinopathy, were]), verbo([found]), complemento([in, 'low-income', and, minority, areas])]). relacion([sujeto(['Most', patients, with, untreated, diabetic, retinopathy, were]), verbo([found]), complemento([to, reside, in, areas, where, primary, health, care, is, provided, through, 'Federally', 'Qualified', 'Health', 'Centers'])]). relacion([sujeto(['The', ability, to, identify, the, growing, number, of, diabetic, patients, with, retinopathy, in, 'low-income', areas, will, likely]), verbo([require]), complemento([the, adoption, of, 'cost-effective', screening, technologies, that, are, currently, not, funded, by, 'Medicare', and, 'Medicaid'])]). relacion([sujeto(['Tight', junctions, are, critically, important, for, many, physiological, 'functions,', including, the, maintenance, of, cell, 'polarity,', regulation, of, paracellular, 'permeability,', and, involvement, in, signal, transduction, pathways, to]), verbo([regulate]), complemento([integral, cellular, processes])]). relacion([sujeto(['Furthermore,', tight, junctions, enable, epithelial, cells, to, form, physical, 'barriers,', which]), verbo([act]), complemento([as, an, innate, immune, mechanism, that, can, impede, viral, infection])]). relacion([sujeto(['Viruses,', in, 'turn,']), verbo([have]), complemento([evolved, mechanisms, to, exploit, tight, junction, proteins, to, gain, access, to, cells, or, spread, through, tissues, in, an, infected, host])]). relacion([sujeto(['Claudin', family, proteins, are, integral, components, of, tight, junctions, and, are, thought, to, play, crucial, roles, in]), verbo([regulating]), complemento([their, permeability])]). relacion([sujeto(['Claudins']), verbo([have]), complemento([been, implicated, in, the, infection, process, of, several, medically, important, human, 'pathogens,', including, hepatitis, 'C', 'virus,', dengue, 'virus,', 'West', 'Nile', 'virus,', and, human, immunodeficiency, 'virus,', among, others])]). relacion([sujeto(['A', better, understanding, of, claudins, during, viral, infection, may]), verbo([provide]), complemento([insight, into, physiological, roles, of, claudins, and, uncover, novel, therapeutic, antiviral, strategies])]). relacion([sujeto(['In', 'Finland,', forensic, age, assessment, is, strictly]), verbo([regulated]), complemento([by, legislation])]). relacion([sujeto(['According', to, the, 'Aliens', 'Act', '(', 301, /, 2004, ')', and, the, amendment, of, the, 'Act', '(', 549, /, 2010, ')', ',', the, police, 'authorities,', the, frontier, guard, 'authorities,', and, the, immigration, authorities]), verbo([have]), complemento([the, right, to, refer, asylum, seekers, to, the, 'University', of, 'Helsinki,', 'Department', of, 'Forensic', 'Medicine,', for, age, assessment])]). relacion([sujeto(['The', current, legislation, on, forensic, age, assessment]), verbo([has]), complemento([been, well, received, and, approved])]). relacion([sujeto(['Radiological', and, other, examinations, can, be, performed, in, different, parts, of, 'Finland,', but, the, forensic, odontologist, at, the, 'University', of, 'Helsinki', is, always]), verbo([involved]), complemento([in, the, process, and, ensures, joint, quality, standards, for, the, forensic, age, assessment])]). relacion([sujeto(['In', 2000, ',', 'Congress', passed, the, 'Breast', and, 'Cervical', 'Cancer', 'Prevention', and, 'Treatment', 'Act', '(', 'BCCPTA)', to]), verbo([provide]), complemento([coverage, through, 'Medicaid', to, women, who, screened, positive, for, breast, and, cervical, cancer])]). relacion([sujeto(['We', aimed, to, determine, if, 'late-stage', breast, cancer, prevalence]), verbo([decreased]), complemento([among, 'Oklahoma', women, after, passage, of, 'BCCPTA'])]). relacion([sujeto(['To', date, 'adult-onset', asthmatic, patients, who, lack, a, clear, stridor, and, show, prolonged, coughs, and, chest, discomfort]), verbo([caused]), complemento([by, 'small-airways', dysfunction, have, increased])]). relacion([sujeto(['Moreover,', mean, daily, inhalation, doses, were]), verbo([decreased]), complemento([from, 5.0, to, 4.3, in, 'BUD/FM-DPI', group, and, decreased, from, 5.7, to, 3.7, in, 'FP/SM-pMDI', group])]). relacion([sujeto(['Slow', and, deep, inhalation, of, 'FP/FM-pMDI', is, effective, in, many, asthmatic, patients, who]), verbo([have]), complemento([prolonged, 'small-airways', dysfunction])]). relacion([sujeto(['After', ascending, aortic, 'replacement,', a, remaining, 're-entry', tear, in, the, distal, brachiocephalic, branches, may]), verbo([act]), complemento([as, an, entry, and, result, in, a, patent, false, lumen, in, the, aortic, arch])]). relacion([sujeto(['Brachiocephalic', branch, 're-entry', was, a, significant, risk, factor, for, a, late]), verbo([increase]), complemento([in, the, aortic, arch, diameter, greater, than, 10, mm, '(', 'P=0'])]). relacion([sujeto(['More', than, a, decade, of, research]), verbo([has]), complemento([supported, a, robust, 'consensus:', 'Acute', stress, impairs, memory, retrieval])]). relacion([sujeto(['To', bolster, 'memory,', we, used, retrieval, 'practice,', or, the]), verbo([act]), complemento([of, taking, practice, tests])]). relacion([sujeto(['Twenty-four', hours, 'later,', we]), verbo([induced]), complemento([stress, in, half, of, the, participants, and, assessed, subsequent, memory, performance])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, the, effects, of, stress, on, memory, retrieval, may, be, contingent, on, the, strength, of, the, memory, representations, themselves])]). relacion([sujeto(['Fee', for, service, methodology, is, often, implicated, as, a]), verbo([cause]), complemento([of, this, exceedingly, high, figure])]). relacion([sujeto(['MACRA']), verbo([has]), complemento([dramatic, implications, for, all, 'US', based, healthcare, providers])]). relacion([sujeto(['Neurointerventionalists', will, predominantly]), verbo([participate]), complemento([in, 'MIPS'])]). relacion([sujeto(['In', 'October', 2016, ',', the, 'Centers', for, 'Medicare', and, 'Medicaid', 'Services', '(', 'CMS)']), verbo([released]), complemento([a, final, rule, for, 'MACRA', 'implementation,', providing, greater, clarity, regarding, 2017, requirements])]). relacion([sujeto(['The', final, rule]), verbo([provides]), complemento([a, range, of, options, for, easing, 'MIPS', reporting, requirements, in, the, first, performance, year])]). relacion([sujeto(['Nonetheless,', taking, the, newly, offered, '\'', minimum, 'possible\'', approach, toward, meeting, the, requirements, will, still]), verbo([have]), complemento([negative, consequences, for, providers])]). relacion([sujeto(['The', objective, was, to, examine, whether, 'Word', 'Clouds', can]), verbo([act]), complemento([as, a, heuristic, approach, to, encourage, a, narrative, orientation, to, medicine])]). relacion([sujeto(['The', elicitation, of, stories, for, the, 'Word', 'Cloud']), verbo([promotes]), complemento([narrative, attention, to, the, patient, as, a, whole, person])]). relacion([sujeto(['Engaging', in, the, process, of, making, a, 'Word', 'Cloud', can]), verbo([promote]), complemento([a, narrative, orientation, to, 'medicine,', forging, 'connections,', making, meaning, through, reminiscence, and, leaving, a, legacy, of, a, loved, one])]). relacion([sujeto(['Cell', adhesion, molecules, '(', 'CAM)', play, essential, roles, in, the, central, nervous, 'system,', where, some, families, are]), verbo([involved]), complemento([in, synaptic, development, and, function])]). relacion([sujeto(['These', synaptic, adhesion, molecules, '(', 'SAMs)', are]), verbo([involved]), complemento([in, the, regulation, of, synaptic, 'plasticity,', and, the, formation, of, neuronal, networks])]). relacion([sujeto(['Recent', findings, from, studies, examining, the, consequences, of, sleep]), verbo([loss]), complemento([suggest, that, these, molecules, are, candidates, to, act, in, sleep, regulation])]). relacion([sujeto(['This', review, highlights, the, experimental, data, that]), verbo([lead]), complemento([to, the, identification, of, 'SAMs', as, potential, sleep, 'regulators,', and, discusses, results, supporting, that, specific, 'SAMs', are, involved, in, different, aspects, of, sleep, regulation])]). relacion([sujeto(['Further,', some, potential, mechanisms, by, which, 'SAMs', may]), verbo([act]), complemento([to, regulate, sleep, are, 'outlined,', and, the, proposition, that, these, molecules, may, serve, as, molecular, machinery, in, the, two, sleep, regulatory, 'processes,', the, circadian, and, homeostatic, 'components,', is, presented])]). relacion([sujeto(['Together,', the, data, argue, that, 'SAMs']), verbo([regulate]), complemento([the, neuronal, plasticity, that, underlies, sleep, and, wakefulness])]). relacion([sujeto(['Scavenger', receptor, 'A', '(', 'SRA)']), verbo([has]), complemento([been, known, as, an, immunosuppressive, factor, and, therefore, therapeutic, inhibition, of, 'SRA', may, be, potentially, exploited, for, cancer, immunotherapy])]). relacion([sujeto(['Our', previously, work]), verbo([suggested]), complemento([that, rhein, may, act, as, an, inhibitor, of, 'SRA', in, reversing, immunosuppression, of, 'SRA', during, 'T', cells, activation])]). relacion([sujeto(['These', three, 'compounds,', particularly, compound, 1, ',', also, known, as, a, natural, product, 'danthron,']), verbo([enhanced]), complemento(['T', cells, 'activation,', indicated, by, increased, transcriptional, activation, of, interleukin, 2, '(', 'Il2)', 'gene,', production, of, 'IL-2', 'protein,', and, proliferation, of, 'T', cells])]). relacion([sujeto(['Compound', 1, showed, a, favorable]), verbo([binding]), complemento([mode, with, the, cysteine, rich, domain, of, 'SRA', protein, compared, to, compound, 2, and, 3])]). relacion([sujeto(['Collectively,', those, results, would]), verbo([provide]), complemento([insight, for, future, design, and, development, of, next, generation, rhein, derivatives, as, 'SRA', inhibitors])]). relacion([sujeto(['Although', conventional, antimicrobial, drugs]), verbo([have]), complemento([been, viewed, as, miraculous, 'cure-alls', for, the, past, 80, 'years,', increasing, antimicrobial, drug, resistance, requires, a, major, and, rapid, intervention])]). relacion([sujeto(['To', continue, to, produce, new, agents, based, on, this, notion, is, 'unacceptable,', and, there, is, an]), verbo([increasing]), complemento([need, for, alternative, approaches, to, the, problem])]). relacion([sujeto(['By', 'contrast,', 'light-activated', molecules, called, photoantimicrobials]), verbo([act]), complemento([locally, via, the, 'in-situ', production, of, highly, reactive, oxygen, 'species,', which, simultaneously, attack, various, biomolecular, sites, in, the, pathogenic, target, and, therefore, offer, both, multiple, and, variable, sites, of, action])]). relacion([sujeto(['This', 'non-specificity', at, the]), verbo([target]), complemento([circumvents, conventional, mechanisms, of, resistance, and, inhibits, the, development, of, resistance, to, the, agents, themselves])]). relacion([sujeto(['However,', clinical, trials, of, these, 'new,', truly, 'broad-spectrum,', and, minimally, toxic, agents]), verbo([have]), complemento([been, 'few,', and, the, funding, for, research, and, development, is, almost, 'non-existent'])]). relacion([sujeto(['Logistic', regression, was, used, to, identify, factors, that]), verbo([increase]), complemento([the, odds, of, a, positive, reimbursement, recommendation])]). relacion([sujeto(['Proven', efficacy, and, safety, were]), verbo([associated]), complemento([with, much, greater, odds, for, a, positive, reimbursement, recommendation, '(', 123.5, and, 42.6, ',', 'respectively)', than, cost, 'factors,', which, may, suggest, that, patient, outcome, is, much, more, important, than, the, results, of, the, 'cost-effectiveness', analysis, '(', odds, ratio, of, 3.5, ')', and, the, general, cost, of, therapy, '(', odds, ratio, of, 3, ')', in, the, analysed, period])]). relacion([sujeto(['Though', 'PD', is, 'multifactorial,', several, epidemiological]), verbo([reports]), complemento([show, an, increased, incidence, of, 'PD', with, 'co-exposure', to, pesticides, such, as, 'Maneb', and, paraquat, '(', 'MP)'])]). relacion([sujeto(['In', 'pesticide-related', 'PD,', mitochondrial, dysfunction, and, 'α-synuclein', oligomers]), verbo([have]), complemento([been, strongly, 'implicated,', but, the, link, between, the, two, has, not, yet, been, understood])]). relacion([sujeto(['Mitochondrial', dysfunction, during, 'PD', pathogenesis]), verbo([leads]), complemento([to, release, of, cytochrome, c, in, the, cytosol])]). relacion([sujeto(['Once', in, the, 'cytosol,', cytochrome, c]), verbo([has]), complemento([one, of, two, 'fates:', 'It', either, binds, to, apaf1, and, initiates, apoptosis, or, can, act, as, a, peroxidase])]). relacion([sujeto(['Experiments', with, 'MP', 'co-exposed', mice, showed, cytochrome, c]), verbo([release]), complemento([in, cytosol, and, its, 'co-localization', with, 'α-synuclein'])]). relacion([sujeto(['Altogether,', these, results, show, that, peroxidase, activity, of, cytochrome, c, contributes, to, 'α-synuclein', radical, formation, and, 'oligomerization,', and, that, 'α-synuclein,', through, its, 'co-localization', with, cytochrome, c, or, on, its, 'own,', affects, several, biological, pathways, which, contribute, to]), verbo([increased]), complemento([neuronal, death, in, an, 'MP-induced', model, of, 'PD'])]). relacion([sujeto(['Youth', trauma, exposure, is]), verbo([associated]), complemento([with, syndemic, 'HIV', risk])]). relacion([sujeto(['Nearly', all, '(', 99.7, '%', ')']), verbo([reported]), complemento([experiencing, at, least, one, 'PTE'])]). relacion([sujeto(['Adolescent', men]), verbo([reported]), complemento([more, violent, 'PTEs', '(', e])]). relacion([sujeto([',', &, 'quot;seen', an]), verbo([act]), complemento([of, violence, in, the, 'community")', whereas, women, reported, more, 'non-violent', 'HIV/AIDS-related', 'PTEs', '(', e])]). relacion([sujeto(['High', 'PTE', score, was, independently]), verbo([associated]), complemento([with, high, food, insecurity, among, adolescent, men, and, women, '(', aOR, =, 2.63, ',', 95, '%', 'CI', =, 1.36, -, 5.09, ;, aOR, =, 2.57, ',', 95, '%', 'CI', =, 1.55, -, 4.26, ',', 'respectively)'])]). relacion([sujeto(['For', 'men,', high, 'PTE', score, was, also]), verbo([associated]), complemento([with, older, age, '(', aOR, =, 1.4, /, 'year,', 95, '%', 'CI', =, 1.21, -, 1.63, ')', ;, and, recently, moving, to, 'Soweto', '(', aOR, =, 2.78, ',', 95, '%', 'CI', =, 1.14, -, 6.76, ')'])]). relacion([sujeto(['Among', 'women,', high, 'PTE', score, was]), verbo([associated]), complemento([with, depression, using, the, 'CES-D', scale, '(', aOR, =, 2.0, ',', 95, '%', 'CI', =, 1.31, -, 3.03, ',', ')', and, inconsistent, condom, use, vs])]). relacion([sujeto(['Among', adolescent, 'women,', associations, with, depression, and, inconsistent, condom, use]), verbo([suggest]), complemento([pathways, for, 'HIV', risk])]). relacion([sujeto(['HIV', prevention, interventions]), verbo([targeting]), complemento([adolescents, must, address, the, syndemics, of, trauma, and, 'HIV', through, the, 'scale-up', of, 'gender-transformative,', 'youth-centred,', 'trauma-informed', integrated, 'HIV', and, mental, health, services])]). relacion([sujeto(['Cancer']), verbo([has]), complemento([become, a, global, burden, due, to, its, high, incidence, and, mortality, 'rates,', with, an, estimated, 14.1, million, cancer, cases, reported, worldwide, in, 2012, particularly, as, a, result, of, metastasis])]). relacion([sujeto(['Metastasis']), verbo([involves]), complemento([two, crucial, 'steps:', adhesion, and, 'invasion,', and, the, 'non-integrin', 'receptor;', the, 37, -, 'kDa/67-kDa', laminin, receptor, 'precursor/', high, affinity, laminin, receptor, '(', 'LRP/LR)', has, been, shown, to, be, overexpressed, on, the, surface, of, tumorigenic, 'cells,', thus, being, implicated, in, the, enhancement, of, these, two, crucial, steps])]). relacion([sujeto(['The', treatment, of, 'AsPC-1', and, 'IMR-32', cells, with, 'IgG1-iS18']), verbo([caused]), complemento([a, significant, reduction, in, the, adhesive, and, invasive, potential, of, the, cells, to, 'laminin-1', and, through, the, 'ECM-like', 'Matrigel™,', respectively])]). relacion([sujeto(['Pearson\'s', correlation, coefficients, indicated, a, high, 'correlation,', thus]), verbo([suggesting]), complemento([a, directly, proportional, relationship, between, cell, surface, 'LRP/LR', levels, and, the, adhesive, and, invasive, potential, of, 'AsPC-1', and, 'IMR-32', cells])]). relacion([sujeto(['These', findings]), verbo([suggest]), complemento([that, through, the, interference, of, the, 'LRP/LR-laminin-1', 'interaction,', the, 'anti-LRP/LR', specific, antibody, 'IgG1-iS18', may, act, as, an, alternative, therapeutic, tool, for, the, treatment, of, metastatic, pancreatic, cancer, and, neuroblastoma])]). relacion([sujeto(['Exposure', to, 2, ',', 3, ',', 7, ',', 8, -, 'tetrachlorodibenzo-p-dioxin', '(', 'TCDD),', a, widespread, highly, toxic, environmental, 'contaminant,']), verbo([suppresses]), complemento([immune, response, and, leads, to, an, increased, susceptibility, to, infectious, agents])]). relacion([sujeto(['In', 'particular,', several, studies]), verbo([have]), complemento([provided, evidence, that, 'TCDD', decreases, resistance, to, numerous, viruses])]). relacion([sujeto(['Moreover,', 'TCDD', could]), verbo([induce]), complemento([an, exacerbation, of, latent, infection, produced, by, 'HIV-1,', 'CMV', or, 'Epstein-Barr', virus])]). relacion([sujeto(['Overall,', the, available, data, support, the, concept, that, 'TCDD', exposure, may]), verbo([act]), complemento([as, an, additional, risk, factor, in, promoting, of, viral, diseases])]). relacion([sujeto(['Student', nurses, value, a, welcoming, workplace, where, staff, and, educators, are, happy, to, help, and]), verbo([have]), complemento([a, positive, attitude, to, student, presence, on, the, wards])]). relacion([sujeto(['More', than, any, other, factors, these, 'ward-based', factors, appear, to]), verbo([have]), complemento([the, strongest, influence, on, student, satisfaction])]). relacion([sujeto(['Reticulon', 3, '(', 'RTN3),', which, is, a, member, of, the, reticulon, family, of, 'proteins,']), verbo([has]), complemento([a, biochemical, function, of, shaping, tubular, endoplasmic, reticulum])]). relacion([sujeto(['RTN3']), verbo([has]), complemento([also, been, found, to, interact, with, 'β-site', amyloid, precursor, protein, cleaving, enzyme, 1, '(', 'BACE1),', which, initiates, the, generation, of, 'β-amyloid', peptides, '(', 'Aβ)', from, amyloid, precursor, protein])]). relacion([sujeto(['Mice', deficient, in, or, overexpressing, 'RTN3']), verbo([have]), complemento([altered, amyloid, deposition, through, effects, on, 'BACE1', expression, and, activity])]). relacion([sujeto(['In', this, 'review,', we, will, summarize, the, current, findings, concerning, the, role, of, 'RTN3', in, 'AD', pathogenesis, and, demonstrate, that, 'RTN3', protein, levels]), verbo([act]), complemento([as, 'age-dependent', modulators, of, 'BACE1', activity, and, 'Aβ', deposition, during, the, pathogenic, progression, of, 'AD'])]). relacion([sujeto(['The']), verbo([increase]), complemento([of, the, 'SAPS', score, in, one, point, increased, the, chance, of, death, in, patients, with, influenza, by, 1.2, '%', '(', 'OR', =, 1.12, 95, '%', 'CI', 1.01, -, 2.976, ')'])]). relacion([sujeto(['The', 'ROC', analysis, indicated, that, cardiovascular, 'diseases,']), verbo([increased]), complemento([urea, values, and, 'SAPS', score, in, combination, act, as, a, good, prognostic, model, for, the, fatal, outcome])]). relacion([sujeto(['Cardiovascular', 'diseases,']), verbo([increased]), complemento([values, of, urea, over, 8.3, 'mmol/l', and, 'SAPS', score, are, independent, predictive, indicators, for, lethal, outcome, in, severe, influenza])]). relacion([sujeto(['Early', identification, of, the, outcome, predictors, in, patients, with, severe, influenza, will, allow, implementation, of, adequate, medical, treatment, and, will, contribute, to]), verbo([decreasing]), complemento([of, mortality, in, patients, with, severe, form, of, influenza])]). relacion([sujeto(['Sorting', nexins, are, 'PX', 'domain-containing', proteins, that]), verbo([bind]), complemento([phospholipids, and, often, act, in, membrane, trafficking, where, they, help, to, select, cargo])]). relacion([sujeto(['Deletions', of, nine, different, sorting, nexins, were, screened, for, mislocalization, of, a, set, of, 'GFP-tagged', membrane, proteins]), verbo([found]), complemento([at, the, plasma, 'membrane,', 'Golgi', or, endosomes])]). relacion([sujeto(['This', identified, 27, proteins, that]), verbo([require]), complemento([one, or, more, sorting, nexins, for, their, correct, 'localization,', 23, of, which, represent, novel, sorting, nexin, cargo])]). relacion([sujeto(['We', identified, cytosolic, domains, of, 'Ear1,', 'Ymd8', and, 'Ymr010w', that]), verbo([conferred]), complemento(['retromer-dependent', sorting, on, a, chimeric, reporter, and, identified, conserved, residues, required, for, this, sorting, in, a, functional, assay])]). relacion([sujeto(['The', 'Center']), verbo([has]), complemento([flourished, as, a, community, psychology, setting, for, 'practice,', 'research,', and, training, for, 39, of, the, 50, &, 'nbsp;years', since, 'Swampscott'])]). relacion([sujeto(['Here', we, investigated, the, potential, of, grifolin, derivatives, from, 'Albatrellus', ovinus, to]), verbo([act]), complemento([as, 'TRPV1', receptor, blockers, and, their, potential, to, serve, as, cosmetic, active, ingredients])]). relacion([sujeto(['The', 'TRPV1', receptor, was]), verbo([activated]), complemento([in, vivo, with, capsaicin, and, noxious, heat, to, investigate, skin, 'reddening,', 'microcirculation,', skin, sensations, and, heat, pain, thresholds])]). relacion([sujeto(['Grifolin', derivatives, extracted, from, 'Albatrellus', ovinus, proved, to]), verbo([inhibit]), complemento([the, 'TRPV1', receptor, in, vitro, and, in, vivo])]). relacion([sujeto(['Besides', suppression, of, the, 'TRPV1', receptor, activity, upon, chemical, stimulation, with, 'capsaicin,', thermal, activation, was, shown, to, be]), verbo([inhibited]), complemento([as, well, by, application, of, cosmetic, formulations, containing, 3, '%', 'Albatrellus', ovinus, extract])]). relacion([sujeto(['This', study, examined, social, influences, on, 3, -, 'year-old', 'children\'s', decisions, to, help, an, experimenter]), verbo([gain]), complemento([another, 'person\'s', attention, '(', 'N = 32)'])]). relacion([sujeto(['Children', were, slower, to, help, the, experimenter, when, the]), verbo([target]), complemento([had, previously, expressed, disinterest, in, attending, to, her])]). relacion([sujeto(['Therefore,', young, 'children\'s', decisions, to]), verbo([act]), complemento([helpfully, incorporate, consideration, for, others, beyond, a, focal, person, with, an, unmet, 'need,', and, they, are, further, constrained, by, 'children\'s', own, comfort, with, the, actions, required, to, help])]). relacion([sujeto(['The', 'Mediterranean', 'Diet', '(', 'MD)']), verbo([has]), complemento([been, proved, to, exert, benefits, with, respect, to, the, maintenance, of, the, redox, 'balance,', and, wine, is, a, representative, component])]). relacion([sujeto(['Bioactive', compounds, such, as, 'polyphenols,', melatonin, and, hydroxytyrosol]), verbo([act]), complemento([as, radical, scavengers, and, regulate, the, oxidation, status, of, organisms])]). relacion([sujeto(['The', repair, of, oxidized, 'DNA', entails, the, removal, of, the, useless, bases, 'and/or', nucleotides, as, well, as, the]), verbo([release]), complemento([of, circulating, nucleotides, and, nucleosides])]). relacion([sujeto(['The', current, research, aims, to, 'elucidate,', for, the, first, 'time,', the, 'DNA', protection, against, oxidative, stress]), verbo([provided]), complemento([by, three, types, of, red, wine, -, relating, it, to, the, intake, of, bioactive, compounds, -, after, the, intake, of, a, serving, of, red, 'wine/must', by, 18, healthy, female, volunteers, during, a, short, term, 'double-blind,', crossover, and, 'placebo-controlled', study])]). relacion([sujeto(['The', results, show, that, the, intake, of, red, wine, and, must, secondarily, reduces, oxidative, stress, and, carcinogenesis, due, to, their, content, of, homovanillic, 'acid,', as, measured, by]), verbo([decreases]), complemento([in, the, plasmatic, concentration, of, 8, -, 'hydroxy-2\'deoxyguanosine,', 8, -, 'hydroxyguanine,', and, 8, -, nitroguanosine])]). relacion([sujeto(['Moreover,', the, intake, of, wine, appears, to, exert, vasodilatory, 'effects,']), verbo([mediated]), complemento([by, the, action, of, nitric, oxide, and, increased, plasma, 'guanosine-3\'-5\'-cyclic', monophosphate, plasmatic, 'levels,', owing, to, the, intake, of, wines, higher, in, melatonin, and, homovanillic, acid])]). relacion([sujeto(['The', unique, ability, of, bats, to]), verbo([act]), complemento([as, reservoir, for, viruses, that, are, highly, pathogenic, to, humans, suggests, unique, properties, and, functional, characteristics, of, their, immune, system])]). relacion([sujeto(['However,', the, lack, of, bat, specific, 'reagents,', in, particular, 'antibodies,']), verbo([has]), complemento([limited, our, knowledge, of, 'bat\'s', immunity])]). relacion([sujeto(['Using', 'cross-reactive', 'antibodies,', we]), verbo([report]), complemento([the, phenotypic, and, functional, characterization, of, 'T', cell, 'subsets,', 'B', and, 'NK', cells, in, the, 'fruit-eating', bat, 'Pteropus', alecto])]). relacion([sujeto(['Interestingly,', 40, '%', of, spleen, 'T', cells]), verbo([expressed]), complemento([constitutively, 'IL-17,', 'IL-22', and, 'TGF-β', 'mRNA,', which, may, indicate, a, strong, bias, towards, the, 'Th17', and, regulatory, 'T', cell, subsets])]). relacion([sujeto(['Furthermore,', the, unexpected, high, number, of, 'T', cells, in, bats, 'BM', could]), verbo([suggest]), complemento([an, important, role, in, 'T', cell, development])]). relacion([sujeto(['Finally,', mitogenic, stimulation]), verbo([induced]), complemento([proliferation, and, production, of, effector, molecules, by, bats, immune, cells])]). relacion([sujeto(['Upon', local, accumulation, in, the, damaged, 'vessels,', 'LPA', can]), verbo([act]), complemento([as, a, potent, activator, for, various, types, of, immune, cells, through, its, specific, membrane, receptors, 'LPA1/3'])]). relacion([sujeto(['LPA', elicits, 'chemotactic,', 'pro-inflammatory', and, apoptotic, effects, that]), verbo([lead]), complemento([to, atherosclerotic, plaque, progression])]). relacion([sujeto(['In', this, study, we, aimed, to]), verbo([inhibit]), complemento(['LPA', signaling, by, means, of, 'LPA1/3', antagonism, using, the, small, molecule, 'Ki16425'])]). relacion([sujeto(['Treatment', with, 'Ki16425', also, resulted, in, reduced, 'CCL2', production, and, 'secretion,', which]), verbo([led]), complemento([to, less, monocyte, and, neutrophil, infiltration])]). relacion([sujeto(['Furthermore,', we]), verbo([provide]), complemento([evidence, that, 'LPA1/3', blockade, enhanced, the, percentage, of, 'non-inflammatory,', 'Ly6C(low)', monocytes, and, 'CD4(+)', 'CD25(+)', 'FoxP3(+)', 'T-regulatory', cells])]). relacion([sujeto(['In', multivariable, linear, regression, 'analysis,', 'Sfrp5,', 'Wnt5a,', 'adiponectin,', chemerin, and, hsCRP, were]), verbo([associated]), complemento([with, both, standard, deviation, 'score-systolic', blood, pressure, '(', 'SDS-SBP)', and, -, diastolic, blood, pressure, '(', 'SDS-DBP)'])]). relacion([sujeto(['These', were, accompanied, by, significant]), verbo([decreases]), complemento([in, hsCRP, and, 'chemerin,', and, significant, increases, in, 'Sfrp5', and, 'adiponectin,', whereas, 'Wnt5a', was, not, changed])]). relacion([sujeto(['Furthermore,', the, changes, in, 'Sfrp5', and, adiponectin]), verbo([act]), complemento([as, partial, mediators, of, the, relationship, between, weight, loss, and, 'BP', reduction, after, controlling, for, covariates])]). relacion([sujeto(['Although', 'Sfrp5,', 'Wnt5a,', 'adiponectin,', chemerin, and, hsCRP, levels, are, correlated, with, 'BP', at, 'baseline,', after, lifestyle, 'intervention,', the, relationship, between, weight]), verbo([loss]), complemento([and, 'BP', reduction, were, partially, mediated, by, changes, in, 'Sfrp5', and, adiponectin, after, controlling, for, covariates])]). relacion([sujeto(['So', we, speculate, that, 'Sfrp5', and, adiponectin, may]), verbo([have]), complemento([some, influence, on, 'BP'])]). relacion([sujeto(['The', efficient, and, precise, delivery, of, siRNA, to]), verbo([target]), complemento([cells, is, critical, to, successful, gene, therapy])]). relacion([sujeto(['While', novel, nanomaterials]), verbo([enhance]), complemento([delivery, 'efficiency,', it, still, remains, challenging, for, precise, gene, delivery, to, overcome, nonspecific, adsorption, and, 'off-target', effect])]). relacion([sujeto(['The', siRNA, is, 'self-assembled', in, an, oligonucleotide, nano, vehicle, that, is, modified, with, a, hairpin, structure, to]), verbo([act]), complemento([as, both, the, '\'', smart, 'key\'', and, the, delivery, carrier])]). relacion([sujeto(['The', 'auto-cleavable', hairpin, structure, can, be]), verbo([activated]), complemento([on, site, at, target, cell, membrane, by, reacting, with, two, aptamers, as, '\'', dual, 'locks\'', 'sequentially,', which, leads, to, 'cell-subtype', discrimination, and, precise, siRNA, delivery, for, high, efficient, gene, silencing])]). relacion([sujeto(['The', success, of, this, strategy, demonstrates, the, precise, delivery, of, siRNA, to, specific]), verbo([target]), complemento([cells, by, controlling, multiple, 'parameters,', thus, paving, the, way, for, application, of, 'RNAi', in, accurate, diagnosis, and, intervention])]). relacion([sujeto(['Porphyromonas', 'gingivalis,', a, keystone, pathogen, in, chronic, 'periodontitis,']), verbo([has]), complemento([been, found, to, associate, with, remote, body, organ, inflammatory, 'pathologies,', including, atherosclerosis, and, 'Alzheimer\'s', disease, '(', 'AD)'])]). relacion([sujeto([gingivalis]), verbo([has]), complemento([a, plethora, of, virulence, 'factors,', much, of, its, pathogenicity, is, surprisingly, related, to, the, overall, immunosuppression, of, the, host])]). relacion([sujeto([gingivalis, aiding, suppression, of, the, 'host\'s', adaptive, immune, system]), verbo([involving]), complemento([manipulation, of, cellular, immunological, 'responses,', specifically, 'T', cells, and, 'B', cells, in, periodontitis, and, related, conditions])]). relacion([sujeto(['In', 'periodontitis,', this, bacterium]), verbo([inhibits]), complemento([the, synthesis, of, 'IL-2', and, increases, humoral, responses])]). relacion([sujeto(['The', 'T', cells, further]), verbo([suppress]), complemento([upregulation, of, programmed, cell, 'death-1', '(', 'PD-1)-receptor', on, 'CD(+)cells', and, its, ligand, 'PD-L1', on, 'CD11b(+)-subset', of, 'T', cells])]). relacion([sujeto(['IL-2', downregulates, genes]), verbo([regulated]), complemento([by, immune, response, and, induces, a, cytokine, pattern, in, which, the, 'Th17', lineage, is, 'favored,', thereby, modulating, the, 'Th17/T-regulatory', cell, '(', 'Treg)', imbalance])]). relacion([sujeto(['The', suppression, of, 'IFN-γ-stimulated']), verbo([release]), complemento([of, 'interferon-inducible', 'protein-10', '(', 'IP-10)', chemokine, ligands, '[', 'ITAC', '(', 'CXCL11)', and, 'Mig', '(', 'CXCL9)]', by, 'P'])]). relacion([sujeto([gingivalis, capsular, serotypes]), verbo([triggers]), complemento([distinct, 'T', cell, responses, and, contributes, to, local, immune, evasion, by, release, of, its, outer, membrane, vesicles])]). relacion([sujeto([gingivalis, reduces, 'Tregs,', transforms, growth, factor, 'beta-1', '(', 'TGFβ-1),', and]), verbo([causes]), complemento([imbalance, in, the, 'Th17', lineage, of, the, 'Treg', population])]). relacion([sujeto([gingivalis, may, affect, the, 'blood-brain', barrier, permeability, and]), verbo([inhibit]), complemento([local, 'IFN-γ', response, by, preventing, entry, of, immune, cells, into, the, brain])]). relacion([sujeto([gingivalis, infection, of, the, brain, likely]), verbo([causing]), complemento([impaired, clearance, of, insoluble, amyloid, and, inducing, immunosuppression])]). relacion([sujeto([gingivalis, may]), verbo([act]), complemento([as, a, keystone, organism, in, periodontitis, and, in, related, systemic, diseases, and, other, remote, body, inflammatory, pathologies])]). relacion([sujeto(['We', argued, that, these, technologies, may, be]), verbo([mediated]), complemento([further, by, discourses, of, ageism, and, ableism, which, can, potentiate, either, the, repressive, or, productive, tendencies, of, these, technologies, resulting, in, either, positive, or, negative, care, experiences, for, the, older, person, 'and/or', their, 'carer,', including, nurses])]). relacion([sujeto(['We', then]), verbo([provided]), complemento([examples, from, research, of, embodied, experiences, of, older, people, with, dementia, and, of, how, nurses, and, other, professionals, utilized, their, 'inter-bodily', experiences, to, inform, acts, of, caring])]). relacion([sujeto(['We', conclude, the, article, by, proposing, that, the]), verbo([act]), complemento([of, caring, is, one, way, nurses, seek, to, reconcile, the, &, 'quot;body-as-representation"', with, the, &, 'quot;body-as-experience"', to, mitigate, the, repressive, effects, of, negative, ageism, and, ableism])]). relacion([sujeto(['The']), verbo([act]), complemento([of, 'caring,', we, 'argue,', is, the, essence, of, caring, enacted, through, the, provision, of, 'person-centred', care, which, evokes, nurses, to, respond, appropriately, to, the, older, 'person\'s', &, 'quot;otherness,"', their, &, 'quot;variation', of, 'being"', while, enabling, them, to, enact, a, continuation, of, themselves, and, their, own, version, of, normality])]). relacion([sujeto(['These', cells, were]), verbo([found]), complemento([in, the, myocardium, with, the, most, pronounced, structural, 'changes:', hypertrophy, of, cardiomyocytes, with, signs, of, their, partial, dedifferentiation])]). relacion([sujeto(['SSTR2-based', 'PET', was, applied, to, 'ACT', of, chimeric, antigen, receptor, '(', 'CAR)', 'T', cells]), verbo([targeting]), complemento([intercellular, adhesion, 'molecule-1,', which, is, overexpressed, in, anaplastic, thyroid, tumors])]). relacion([sujeto(['Timely', 'CAR', 'T', cell, infusions, resulted, in, survival, of, 'tumor-bearing', 'mice,', while, later, infusions]), verbo([led]), complemento([to, uniform, death])]). relacion([sujeto(['In', 'contrast,', nonsurvivors, displayed, unrelenting]), verbo([increases]), complemento([in, tumor, and, 'T', cell, 'burden,', indicating, that, tumor, growth, was, outpacing, 'T', cell, killing])]). relacion([sujeto(['It', is, now, well, established, that, there, is, more, plasticity, than, previously, thought, and, that, astrocytes]), verbo([act]), complemento([as, neural, 'stem/precursor', cells, '(', 'NSPCs)', in, the, subventricular, zone, '(', 'SVZ)'])]). relacion([sujeto(['The', discovery, that, these, 'NSPCs', can, give, rise, to, a, limited, number, of, new, 'neurons,', reactive, astrocytes, and, oligodendrocytes, contributing, to, brain, repair, in, 'CNS', 'disease,']), verbo([has]), complemento([raised, hopes, toward, harnessing, these, cells, for, therapeutic, interventions])]). relacion([sujeto(['In', our, recent, 'study,', we]), verbo([reported]), complemento([that, elevated, 'BMP-2', levels, are, translated, into, an, increase, in, 'Id3', expression, in, adult, 'NSPC', subpopulations, after, cortical, injury])]). relacion([sujeto(['Id3', then]), verbo([heterodimerizes]), complemento([with, the, basic, 'helix-loop-helix', transcription, factor, 'E47', and, releases, the, 'E47-mediated', repression, of, 'astrocyte-specific', gene, expression])]). relacion([sujeto(['We', believe, that, understanding, the, in, vivo, differentiation, potential, and, the, molecular, underpinnings, of, 'NSPCs', in, the, adult, mammalian, brain, will, help, us, to, evaluate, their, contributions, to, brain, repair, and, may]), verbo([lead]), complemento([to, new, concepts, in, treating, human, 'CNS', diseases])]). relacion([sujeto(['Coronary', artery, disease, '(', 'CAD)', and, its, complication, remain, the]), verbo([leading]), complemento([cause, of, mortality, in, industrialized, countries, despite, great, advances, in, terms, of, 'diagnosis,', 'prognosis,', and, treatment, options])]). relacion([sujeto(['MicroRNAs', '(', 'miRNAs),', small, noncoding, 'RNAs,']), verbo([act]), complemento([as, posttranscriptional, gene, expression, modulators, and, have, been, implicated, as, key, regulators, in, several, physiological, and, pathological, processes, linked, to, 'CAD'])]). relacion([sujeto(['Circulating', miRNAs]), verbo([have]), complemento([been, evaluated, as, promising, novel, biomarkers, of, 'CAD,', acute, coronary, 'syndromes,', and, acute, myocardial, 'infarction,', with, prognostic, implications])]). relacion([sujeto(['Several', challenges, related, to, technical, 'aspects,', miRNAs, 'normalization,', drugs, 'interaction,', and, quality]), verbo([reporting]), complemento([of, statistical, multivariable, analysis, of, the, miRNAs, observational, studies, remain, unresolved])]). relacion([sujeto(['Through', this, review, we, will]), verbo([provide]), complemento([clinicians, with, a, concise, overview, of, the, pros, and, cons, of, microRNAs])]). relacion([sujeto(['They']), verbo([act]), complemento([by, increasing, the, activity, of, the, 'membrane-bound', enzyme])]). relacion([sujeto(['All', the, three, 'Porphyrin', compounds]), verbo([increased]), complemento([the, activity, of, erythrocyte, 'Na(+),', 'K(+)-ATPase'])]). relacion([sujeto(['Previous', studies]), verbo([have]), complemento([found, that, predators, utilise, habitat, corridors, to, ambush, prey, moving, through, them])]). relacion([sujeto(['In', the, marine, 'environment,', coastal, channels, effectively]), verbo([act]), complemento([as, habitat, corridors, for, prey, 'movements,', and, sightings, of, predators, in, such, areas, suggest, that, they, may, target, these, for, foraging])]). relacion([sujeto(['For', marine, predators, that, must]), verbo([find]), complemento([prey, that, is, often, patchy, and, widely, 'distributed,', the, underlying, temporal, predictability, in, potential, foraging, opportunities, in, marine, corridors, may, be, important, drivers, in, their, use])]). relacion([sujeto(['In', the, marine, 'environment,', narrow, channels, may]), verbo([act]), complemento([as, 'corridors,', and, sightings, of, predators, suggest, that, they, may, target, these, for, foraging])]). relacion([sujeto(['This', highlights, the, importance, of, narrow, channels, for, marine, predators, and]), verbo([suggests]), complemento([that, this, usually, 'wide-ranging', predator, may, restrict, its, geographic, range, to, forage, in, the, channel, as, a, result, of, increased, prey, availability, 'and/or', foraging, efficiency, driven, by, water, movements, through, the, narrow, corridor])]). relacion([sujeto(['The', 'APOBEC3', '(', 'A3)', 'enzymes,', 'A3G', and, 'A3F,', are, coordinately]), verbo([expressed]), complemento([in, 'CD4+', 'T', cells, and, can, become, coencapsidated, into, 'HIV-1', 'virions,', primarily, in, the, absence, of, the, viral, infectivity, factor, '(', 'Vif)'])]). relacion([sujeto(['A3F', and, 'A3G', are, deoxycytidine, deaminases, that]), verbo([inhibit]), complemento(['HIV-1', replication, by, inducing, guanine, to, adenine, hypermutation, through, deamination, of, cytosine, to, form, uracil, in, '(', -, ')', 'DNA'])]). relacion([sujeto(['Using', size, exclusion, 'chromatography,', rotational, 'anisotropy,', and, in, vitro, deamination, assays, we, demonstrate, that, 'A3F']), verbo([promotes]), complemento(['A3G', deamination, activity, by, forming, an, 'A3F/G', 'hetero-oligomer,', in, the, absence, of, 'RNA,', which, is, more, efficient, at, deaminating, cytosines])]). relacion([sujeto(['Further,', 'A3F']), verbo([caused]), complemento([the, accumulation, of, shorter, reverse, transcripts, due, to, decreasing, reverse, transcriptase, 'efficiency,', which, would, leave, 'single-stranded', '(', -, ')', 'DNA', exposed, for, longer, periods, of, time, enabling, more, deamination, events, to, occur])]). relacion([sujeto(['Although', 'A3G', and, 'A3F', are, known, to, function, alongside, each, 'other,', these, data]), verbo([provide]), complemento([evidence, for, an, 'A3F/G', 'hetero-oligomeric', 'A3', with, unique, properties, when, compared, to, each, individual, counterpart])]). relacion([sujeto(['The', 'APOBEC3', enzymes, 'APOBEC3F', and, 'APOBEC3G']), verbo([act]), complemento([as, a, barrier, to, 'HIV-1', replication, in, the, absence, of, the, 'HIV-1', viral, infectivity, factor, '(', 'Vif)', protein])]). relacion([sujeto(['After', 'APOBEC3', enzymes, are, encaspidated, into, virions, they, deaminate, cytosines, in, '(', -, ')', 'DNA', which, forms, promutagenic, uracils, that]), verbo([induce]), complemento([transition, mutations, or, proviral, 'DNA', degradation])]). relacion([sujeto(['Even', in, the, presence, of, 'Vif,', footprints, of, 'APOBEC3-catalyzed', deaminations, are]), verbo([found]), complemento([demonstrating, that, 'APOBEC3s', still, have, discernable, activity, against, 'HIV-1', in, infected, individuals])]). relacion([sujeto(['The', data, demonstrate, than, an, 'APOBEC3F/APOBEC3G', 'hetero-oligomer', can, form, that]), verbo([has]), complemento([unique, properties, compared, to, each, 'APOBEC3', alone])]). relacion([sujeto(['This', 'hetero-oligomer']), verbo([has]), complemento([increased, efficiency, of, virus, 'hypermutation,', raising, the, idea, that, we, may, still, not, fully, realize, the, antiviral, mechanisms, of, endogenous, 'APOBEC3', enzymes])]). relacion([sujeto(['Hetero-oligomerization', may, be, a, mechanism, to]), verbo([increase]), complemento([their, antiviral, activity, in, the, presence, of, 'Vif'])]). relacion([sujeto(['Human', immunodeficiency, virus, '(', 'HIV-1)', entry, into, cells, is]), verbo([mediated]), complemento([by, the, viral, envelope, glycoproteins, '(', 'Env),', a, trimer, of, three, gp120, exterior, glycoproteins, and, three, gp41, transmembrane, glycoproteins])]). relacion([sujeto(['The', metastable, 'Env', is]), verbo([triggered]), complemento([to, undergo, 'entry-related', conformational, changes, when, gp120, binds, sequentially, to, the, 'receptors,', 'CD4', and, 'CCR5,', on, the, target, cell])]). relacion([sujeto(['Small-molecule', 'CD4-mimetic', compounds, '(', 'CD4mc)']), verbo([bind]), complemento([gp120, and, act, as, competitive, inhibitors, of, 'gp120-CD4', engagement])]). relacion([sujeto(['Some', 'CD4mc']), verbo([have]), complemento([been, shown, to, trigger, 'Env', 'prematurely,', initially, activating, 'Env', 'function,', followed, by, rapid, and, irreversible, inactivation])]). relacion([sujeto(['One', 'CD4mc']), verbo([bound]), complemento([per, 'Env', trimer, activated, 'HIV-1', infection])]). relacion([sujeto(['Envs', with, two, 'CD4mc']), verbo([bound]), complemento([were, activated, for, infection, of, 'CD4-negative,', 'CCR5-positive', 'cells,', but, the, infection, of, 'CD4-positive,', 'CCR5-positive', cells, was, inhibited])]). relacion([sujeto(['Virus', was, inactivated, when, all, three, 'Env', protomers, were, occupied, by, the, 'CD4mc,', and, gp120, shedding, from, the, 'Env', trimer, was]), verbo([increased]), complemento([in, the, presence, of, some, 'CD4mc'])]). relacion([sujeto(['Env', reactivity, and, the, 'on-rates', of, 'CD4mc']), verbo([binding]), complemento([to, the, 'Env', trimer, were, found, to, be, important, determinants, of, the, potency, of, activation, and, entry, inhibition])]). relacion([sujeto(['Cross-sensitization', of, 'Env', protomers, that, do, not]), verbo([bind]), complemento([the, 'CD4mc', to, neutralization, by, an, 'anti-V3', antibody, was, not, evident])]). relacion([sujeto(['The', trimeric, envelope, glycoproteins, of, the, human, immunodeficiency, virus, '(', 'HIV-1)']), verbo([mediate]), complemento([virus, entry, into, host, cells])]). relacion([sujeto(['Binding', to, the, host, cell, 'receptors,', 'CD4', and, 'CCR5,']), verbo([trigger]), complemento([changes, in, the, conformation, of, the, 'HIV-1', envelope, glycoprotein, trimer, important, for, virus, entry])]). relacion([sujeto(['Small-molecule', 'CD4-mimetic', compounds]), verbo([inhibit]), complemento(['HIV-1', infection, by, multiple, 'mechanisms:', 1, ')', 'Direct', blockade, of, the, interaction, between, the, gp120, exterior, envelope, glycoprotein, and, 'CD4;', 2, ')', 'Premature', triggering, of, conformational, changes, in, the, envelope, 'glycoproteins,', leading, to, irreversible, 'inactivation;', and, 3, ')', 'Exposure', of, cryptic, epitopes, to, 'antibodies,', allowing, virus, neutralization])]). relacion([sujeto(['The', consequences, of, the]), verbo([binding]), complemento([of, the, 'CD4-mimetic', compound, to, the, 'HIV-1', envelope, glycoproteins, depends, upon, how, many, of, the, three, subunits, of, the, trimer, are, bound, and, upon, the, propensity, of, the, envelope, glycoproteins, to, undergo, conformational, changes])]). relacion([sujeto(['A', small, fraction, of, the, cleaved, 'IL-37']), verbo([binds]), complemento(['SMAD-3,', translocates, to, the, 'nucleus,', and, suppresses, transcription, of, several, proinflammatory, genes])]). relacion([sujeto(['They']), verbo([bind]), complemento(['IL-18Rα', chain, '(', also, used, by, 'IL-18', as, a, receptor, 'subunit)', and, recruit, 'Toll/IL-1R', '(', 'TIR)-8', for, transducing, intracellular, signaling])]). relacion([sujeto(['IL-37']), verbo([suppresses]), complemento([activation, of, 'NF-κB', and, 'MAPK', and, activates, 'Mer-PTEN-DOK', pathway])]). relacion([sujeto(['It', negatively]), verbo([regulates]), complemento([signaling, mediated, by, 'TLR', 'agonists,', proinflammatory, 'cytokines,', and, 'IL-1RF', ligands])]). relacion([sujeto(['It', also, affects, cell, metabolism, by]), verbo([inhibiting]), complemento(['mTOR,', 'GSK-3α/β,', and, activating, 'AMPK'])]). relacion([sujeto(['Despite', having, the, ability, to, dampen, its, 'host\'s', immune, 'responses,', the, cytokine]), verbo([has]), complemento([been, shown, to, exert, antitumor, 'effects,', and, it, has, been, suggested, that, it, may, act, as, a, prognostic, marker, in, a, variety, of, human, cancers])]). relacion([sujeto(['Recent', studies]), verbo([have]), complemento([suggested, that, 'IL-37', may, represent, a, novel, therapeutic, tool, in, patients, with, cancer])]). relacion([sujeto(['In', this, 'review,', we]), verbo([provide]), complemento([an, overview, of, the, cytokine, 'biology,', discuss, recent, advances, made, in, unraveling, its, 'anti-cancer', 'effects,', and, suggest, guidelines, for, future, research])]). relacion([sujeto(['RNA-DNA', hybrids, are, a, major, internal]), verbo([cause]), complemento([of, 'DNA damage', within, 'cells,', and, their, degradation, by, 'RNase', 'H', enzymes, is, important, for, maintaining, genomic, stability])]). relacion([sujeto(['In', 'contrast,', overexpressing, 'RNase', 'H1', destabilizes, these, 'hybrids,']), verbo([leading]), complemento([to, excessive, strand, resection, and, 'RPA', recruitment, and, to, severe, loss, of, repeat, regions, around, 'DSBs'])]). relacion([sujeto(['Our', study, challenges, the, existing, model, of, 'HR-mediated', 'DSB', repair, and]), verbo([reveals]), complemento([a, surprising, role, for, 'RNA-DNA', hybrids, in, maintaining, genomic, stability])]). relacion([sujeto(['Neighborhood', walkability]), verbo([has]), complemento([been, shown, to, be, associated, with, walking, behavior])]). relacion([sujeto(['Participants']), verbo([reported]), complemento([past, week, 'WT', frequency])]). relacion([sujeto(['The', concept, and, methods, of, space, syntax]), verbo([provide]), complemento([a, novel, approach, to, further, understanding, how, 'urban design', influences, walking, behaviors])]). relacion([sujeto(['Many', 'malaria-endemic', countries]), verbo([have]), complemento([implemented, national, community, health, worker, '(', 'CHW)', programmes, to, serve, remote, populations, that, have, poor, access, to, malaria, diagnosis, and, treatment])]). relacion([sujeto(['In', southwest, 'Uganda,', this, study, examined, whether, 'CHWs', referred, children, according, to, training, guidelines, and, described, factors]), verbo([associated]), complemento([with, adherence, to, the, referral, guideline])]). relacion([sujeto(['All', 'CHWs', were, trained, to, prescribe, 'artemisinin-based', combination, therapy, '(', 'ACT)', and]), verbo([recognize]), complemento([symptoms, in, children, that, required, immediate, referral, to, the, nearest, health, centre])]). relacion([sujeto(['Factors']), verbo([associated]), complemento([with, adherence, were, examined, with, logistic, regression, models])]). relacion([sujeto(['In', the, 'moderate-to-high', transmission, 'setting,', day, and, season, of, visit, were, also]), verbo([associated]), complemento([with, the, likelihood, of, adherence, to, the, referral, 'guidelines,', but, not, in, the, low, transmission, setting])]). relacion([sujeto(['As', many, countries, scale, up, 'CHW', 'programmes,', routine, monitoring, of]), verbo([reported]), complemento([data, should, be, examined, carefully, to, assess, whether, 'CHWs', adhere, to, referral, guidelines, and, take, remedial, actions, where, required])]). relacion([sujeto(['To', date, no, study, with, full, national, coverage]), verbo([has]), complemento([examined, the, pattern, of, hospital, repeated, presentations, due, to, 'self-harm', among, young, people])]). relacion([sujeto(['The', total, sample, comprised, 28, ',', 700, individuals]), verbo([involving]), complemento([42, ',', 642, presentations])]). relacion([sujeto(['Age', was]), verbo([associated]), complemento([with, repetition, only, among, 'females,', in, particular, adolescents, '(', 15, -, 19, years, 'old)', were, at, higher, risk, than, young, emerging, adults, '(', 20, -, 24, years, 'old)'])]). relacion([sujeto(['Repeated', 'self-harm', risk]), verbo([increased]), complemento([significantly, with, the, number, of, previous, 'self-harm', episodes])]). relacion([sujeto(['Time', between, second, and, third, presentation]), verbo([increased]), complemento([compared, to, time, between, first, and, second, presentation, among, low, frequency, repeaters, '(', patients, with, 3, presentations, only, within, 1, year, following, a, first, 'presentation)'])]). relacion([sujeto(['The', same, time, period]), verbo([decreased]), complemento([among, high, frequency, repeaters, '(', patients, with, at, least, 4, to, more, than, 30, 'presentations)'])]). relacion([sujeto(['Self-cutting', was, the, method]), verbo([associated]), complemento([with, the, highest, risk, of, 'self-harm', repetition])]). relacion([sujeto(['To']), verbo([prevent]), complemento([risk, of, repeated, 'self-harm', in, young, 'people,', all, individuals, presenting, at, emergency, departments, due, to, 'self-harm', should, be, provided, with, a, risk, assessment, including, psychosocial, 'characteristics,', history, of, 'self-harm', and, time, between, first, presentations])]). relacion([sujeto(['An']), verbo([increase]), complemento([in, the, activity, of, the, 'pituitary-gonad', axis, '(', 'PG-axis)', and, gonad, development, are, essential, for, the, onset, of, spawning, migration, in, teleosts])]). relacion([sujeto(['We', hypothesized, that, gonadotropin]), verbo([releasing]), complemento([hormones, receptor, 2, '(', 'GnRH-R2),', which, together, produce, a, signal, that, interacts, with, the, 'PG-axis,', may, help, to, regulate, spawning, migration, processes])]). relacion([sujeto(['We']), verbo([found]), complemento([strong, relationships, between, all, of, these, indices])]). relacion([sujeto(['The', results, indicate, that, 'GnRH-R2', could]), verbo([act]), complemento([together, to, promote, spawning, during, the, anadromous, migration])]). relacion([sujeto(['The', 'ubiquitin-proteasome', pathway]), verbo([has]), complemento([been, found, to, play, a, fundamental, role, in, the, development, of, several, 'pathologies,', from, cancer, to, neurodegenerative, 'diseases,', or, even, retroviral, infections])]). relacion([sujeto(['Recently,', a, number, of, molecules, of, natural, 'origin,', as, well, as, natural, product, 'derivatives,']), verbo([have]), complemento([been, described, as, proteasome, inhibitors])]). relacion([sujeto(['Most', of, these, molecules, directly, block, one, or, more, catalytic, sites, of, the, 20, 'S', 'proteasome,', but, some, of, them]), verbo([act]), complemento([upstream, of, proteolytic, 'degradation,', for, 'instance,', inhibiting, the, ubiquitin, tagging, process])]). relacion([sujeto(['With', several, of, these, modulators, of, the, 'ubiquitin-proteasome', system, under, clinical, 'trials,', we, hope, that, the, next, few, years]), verbo([lead]), complemento([to, the, development, of, new, pharmaceutical, drugs, and, characterization, of, new, proteasome, inhibitors, of, natural, origin, or, inspiration])]). relacion([sujeto(['Hepatocellular', carcinoma, '(', 'HCC)', is, the, third]), verbo([leading]), complemento([cause, of, cancer, associated, mortality])]). relacion([sujeto(['Accumulating', evidence]), verbo([has]), complemento([shown, that, microRNAs, '(', 'miRNAs)', act, as, critical, factors, for, tumor, recurrence, and, metastasis])]). relacion([sujeto(['MiR-508-5p']), verbo([has]), complemento([been, reported, as, a, 'down-regulated', miRNA, in, the, primary, gastric, cancer, tissues])]). relacion([sujeto(['However,', the, role, of, 'miR-508-5p', on, 'HCC']), verbo([has]), complemento([not, been, well, elucidated])]). relacion([sujeto(['We', then, demonstrated, that, overexpression, of, 'miR-508-5p', attenuated, 'HepG2', cells, proliferation, and, invasion, and]), verbo([induced]), complemento([cell, apoptosis, in, vitro])]). relacion([sujeto(['Furthermore,', our, further, investigations, revealed, that, mesoderm, development, candidate, 1, '(', 'MESDC1)', is, a, potential]), verbo([target]), complemento([of, 'miR-508-5p,', as, well, as, 'miR-508-5p', overexpression, downregulated, 'MESDC1', expression])]). relacion([sujeto(['Overexpression', of, 'MESDC1']), verbo([promoted]), complemento(['HepG2', cells, 'migration,', invasion, and, proliferation, in, vitro])]). relacion([sujeto(['In', 'addition,', 'miR-508-5p', markedly]), verbo([suppressed]), complemento([the, tumor, growth, in, xenograft, 'model,', while, 'MESDC1', promoted, the, tumor, growth, in, xenograft, model])]). relacion([sujeto(['This', study]), verbo([provides]), complemento([new, insight, into, molecular, mechanisms, that, 'miR-508-5p', acts, as, a, tumor, suppressor, by, targeting, 'MESDC1', in, 'HCC', progression])]). relacion([sujeto(['BST2', '(', bone, marrow, stromal, antigen, 2, ')', /, tetherin, is, a, restriction, factor, of, enveloped, 'viruses,', which, blocks, the]), verbo([release]), complemento([of, viral, particles])]). relacion([sujeto(['We']), verbo([report]), complemento([that, 'BST2', and, 'Vpu', are, present, in, 'LC3-positive', compartments])]). relacion([sujeto(['We']), verbo([found]), complemento([that, 'Vpu', selectively, interacts, with, the, 'ATG8', ortholog, 'LC3C', through, the, 'Vpu', 'L63VEM66', sequence])]). relacion([sujeto(['This', sequence, is]), verbo([required]), complemento([for, 'Vpu', to, antagonize, 'BST2', restriction])]). relacion([sujeto(['LC3C', expression, favors, the, removal, of, 'BST2', from, the, 'HIV-1', budding, 'site,', and, thus, 'HIV-1']), verbo([release]), complemento([in, 'BST2-expressing', cells])]). relacion([sujeto(['Additionally,', 'ATG5', and, beclin, 1, /, 'ATG6,', but, not, all, the, components, of, the, autophagy, 'pathway,']), verbo([act]), complemento([with, 'LC3C', to, facilitate, 'Vpu', antagonism, of, 'BST2', restriction])]). relacion([sujeto(['The', gene, junction, partitioning, the, viral, glycoproteins, 'E1', and, 'E2', displays, concurrent, sequence, evolution, with, the, 3, '\'', -, end, of, 'E1', highly]), verbo([conserved]), complemento([and, the, 5, '\'', -, end, of, 'E2', highly, heterogeneous])]). relacion([sujeto(['This', gene, junction, is, also, believed, to, contain, structured, 'RNA', 'elements,', with, a, growing, body, of, evidence]), verbo([suggesting]), complemento([that, such, structures, can, act, as, an, additional, level, of, viral, replication, and, transcriptional, control])]). relacion([sujeto(['We']), verbo([have]), complemento([previously, used, ultradeep, pyrosequencing, to, analyze, an, amplicon, library, spanning, the, 'E1/E2', gene, junction, from, a, treatment, naïve, patient, where, samples, were, collected, over, 10, years, of, chronic, 'HCV', infection])]). relacion([sujeto(['During', this, timeframe, maintenance, of, an, 'in-frame', 'insertion,', recombination, and, humoral, immune]), verbo([targeting]), complemento([of, discrete, virus, 'sub-populations', was, reported])]). relacion([sujeto(['Overtime,', the, number, of, codons, actively, mutating]), verbo([decreases]), complemento([for, all, virus, groupings])]). relacion([sujeto(['We', identify, strong, synonymous, 'co-variation', between, codon, sites, in, a, group, of, sequences, harbouring, a, 3, bp, 'in-frame', insertion, and, propose, that, synonymous, mutation]), verbo([acts]), complemento([to, stabilize, the, 'RNA', structural, backbone])]). relacion([sujeto(['Birth', defects, are, among, the]), verbo([leading]), complemento([causes, of, infant, mortality, and, contribute, substantially, to, illness, and, 'long-term', disability])]). relacion([sujeto(['Defects', in, 'Bone', 'Morphogenetic', 'Protein', '(', 'BMP)', signaling, are]), verbo([associated]), complemento([with, cleft, 'lip/palate'])]). relacion([sujeto(['Many', craniofacial, syndromes, are]), verbo([caused]), complemento([by, defects, in, signaling, pathways, that, pattern, the, cranial, neural, crest, cells, '(', 'CNCCs)', along, the, 'dorsal-ventral', axis])]). relacion([sujeto(['For', 'example,', auriculocondylar, syndrome, is]), verbo([caused]), complemento([by, impaired, 'Endothelin-1', '(', 'Edn1)', 'signaling,', and, 'Alagille', syndrome, is, caused, by, defects, in, 'Jagged-Notch', signaling])]). relacion([sujeto(['The', 'BMP,', 'Edn1,', and, 'Jag1b', pathways, intersect, because, 'BMP', signaling, is]), verbo([required]), complemento([for, ventral, edn1, expression, 'that,', in, 'turn,', restricts, jag1b, to, dorsal, 'CNCC', territory])]). relacion([sujeto(['In', 'zebrafish,', the, scaffolding, protein, 'Wdr68', is]), verbo([required]), complemento([for, edn1, expression, and, subsequent, formation, of, the, ventral, 'Meckel\'s', cartilage, as, well, as, the, dorsal, 'Palatoquadrate'])]). relacion([sujeto(['Here', we]), verbo([report]), complemento([that, wdr68, activity, is, required, between, the, 17, -, somites, and, 'prim-5', 'stages,', that, edn1, functions, downstream, of, 'wdr68,', and, that, wdr68, activity, restricts, 'jag1b,', 'hey1,', and, grem2, expression, from, ventral, 'CNCC', territory])]). relacion([sujeto(['We', also]), verbo([found]), complemento([that, the, 'BMP', agonist, isoliquiritigenin, '(', 'ISL)', can, partially, rescue, lower, jaw, formation, and, edn1, expression, in, wdr68, mutants])]). relacion([sujeto(['However,', we]), verbo([found]), complemento([no, significant, defects, in, 'BMP', reporter, induction, or, 'pSmad1/5', accumulation, in, wdr68, mutant, cells, or, zebrafish])]). relacion([sujeto(['Here', we, further]), verbo([report]), complemento([that, 'TGF-β', interference, with, 'BMP', signaling, was, greater, in, wdr68, mutant, cells, relative, to, control, cells])]). relacion([sujeto(['To', determine, whether, interference, might, also]), verbo([act]), complemento([in, 'vivo,', we, treated, wdr68, mutant, zebrafish, embryos, with, the, 'TGF-β', signaling, inhibitor, 'SB431542', and, found, partial, rescue, of, edn1, expression, and, craniofacial, development])]). relacion([sujeto(['Together', these, findings]), verbo([reveal]), complemento([an, indirect, role, for, 'Wdr68', in, the, 'BMP-Edn1-Jag1b', signaling, hierarchy, and, 'dorso-anterior', expression, of, 'dlx1a/2a'])]). relacion([sujeto([8, p, deletion, was]), verbo([found]), complemento([in, 2, ',', 581, of, 7, ',', 17, cancers, '(', 36.8, '%', ')', ',', and, was, linked, to, unfavorable, tumor, phenotype])]). relacion([sujeto([8, p, deletion]), verbo([increased]), complemento([from, 29.5, '%', in, 4, ',', 456, pT2, and, 47.8, '%', in, 1, ',', 598, pT3a, to, 53.0, '%', in, 931, 'pT3b-pT4', cancers, '(', 'P', &, 'lt;', 0, ',', 1, ')'])]). relacion([sujeto(['In', 'summary,', 8, p, deletion, is, an, independent, prognostic, parameter, in, prostate, cancer, that, may]), verbo([act]), complemento([synergistically, with, 'PTEN', deletions])]). relacion([sujeto(['Even', statistically, independent, prognostic, biomarkers, like, 8, p, may]), verbo([have]), complemento([limited, clinical, impact, in, morphologically, well, defined, high, or, low, risk, cancers])]). relacion([sujeto(['RNA', helicase, 'Brr2', is, implicated, in, multiple, phases, of, 'pre-mRNA', splicing, and, thus]), verbo([requires]), complemento([tight, regulation])]). relacion([sujeto(['Furthermore,', it, can, be]), verbo([regulated]), complemento([in, trans, by, the, 'Jab1', domain, of, the, 'Prp8', 'protein,', which, can, inhibit, 'Brr2', by, intermittently, inserting, a, 'C-terminal', tail, in, the, 'enzyme\'s', 'RNA-binding', tunnel, or, activate, the, helicase, after, removal, of, this, tail])]). relacion([sujeto(['Presently', it, is, 'unclear,', whether, these, regulatory, mechanisms, functionally]), verbo([interact]), complemento([and, to, which, extent, they, are, evolutionarily, conserved])]). relacion([sujeto(['Here,', we]), verbo([report]), complemento([crystal, structures, of, 'Saccharomyces', cerevisiae, and, 'Chaetomium', thermophilum, 'Brr2-Jab1', 'complexes,', demonstrating, that, 'Jab1-based', inhibition, of, 'Brr2', presumably, takes, effect, in, all, eukaryotes, but, is, implemented, via, 'organism-specific', molecular, contacts])]). relacion([sujeto(['Moreover,', the, structures, show, that, 'Brr2', 'auto-inhibition', can]), verbo([act]), complemento([in, concert, with, 'Jab1-mediated', 'inhibition,', and, suggest, that, the, 'N-terminal', region, influences, how, the, 'Jab1', 'C-terminal', tail, interacts, at, the, 'RNA-binding', tunnel])]). relacion([sujeto(['Systematic', 'RNA']), verbo([binding]), complemento([and, unwinding, studies, revealed, that, the, 'N-terminal', region, and, the, 'Jab1', 'C-terminal', tail, specifically, interfere, with, accommodation, of, 'double-stranded', and, 'single-stranded', regions, of, an, 'RNA', 'substrate,', 'respectively,', mutually, reinforcing, each, other])]). relacion([sujeto(['Additionally,', such, analyses, show, that, regulation, based, on, the, 'N-terminal', region]), verbo([requires]), complemento([the, presence, of, the, inactive, 'C-terminal', helicase, cassette])]). relacion([sujeto(['Risk', of, obstetric, complications]), verbo([increases]), complemento([linearly, with, rising, maternal, glycaemia])]). relacion([sujeto([9, '%', could]), verbo([act]), complemento([as, a, pregnancy, risk, marker])]). relacion([sujeto([9, '%', 'HbA1c', could, be, useful, to, identify, women, without, diabetes, mellitus, at]), verbo([increased]), complemento([pregnancy, risk])]). relacion([sujeto([9, '%', was, independently]), verbo([associated]), complemento([with, a, 'three-fold', increased, risk, of, macrosomia, '(', 95, '%', 'CI:', 1.127, -, 8.603, ',', 'p=', 0.028, ')', and, preeclampsia, '(', 95, '%', 'CI:', 1.086, -, 11.532, ',', 'p=', 0.036, ')'])]). relacion([sujeto(['Further', studies, are]), verbo([required]), complemento([to, establish, cutoff, points, adapted, to, each, ethnic, group, and, to, assess, whether, early, detection, and, treatment, are, of, benefit])]). relacion([sujeto(['Hybrids', between, the, 'Arabidopsis', ecotypes, 'C24', and, 'Ler']), verbo([have]), complemento([high, levels, of, hybrid, 'vigour,', 'heterosis,', in, both, biomass, and, seed, yield])]). relacion([sujeto(['In', the, transcriptomes, of, 4, dap, '(', dermatogen, to, 'globular)', and, 6, dap, '(', 'heart)', embryos, from, both, parents, and, 'hybrids,', 95, '%', of]), verbo([expressed]), complemento([genes, were, at, the, 'Mid', 'Parent', 'Value', '(', 'MPV)', and, 95, '%', of, the, genes, with, 'SNPs', between, 'C24', and, 'Ler', retained, the, same, relative, allelic, expression, levels, in, the, hybrids, as, existed, in, the, parents])]). relacion([sujeto(['Amongst', the, genes, which, did, not]), verbo([have]), complemento(['MPV', expression, levels, in, the, hybrids, '(', 'non-additively', expressed, 'genes),', approximately, 40, in, the, globular, embryo, stage, and, 89, in, the, heart, embryos, had, altered, levels, of, transcription, in, both, reciprocal, 'hybrids;', these, genes, could, contribute, to, the, heterotic, phenotype, of, the, hybrid, embryo])]). relacion([sujeto(['Many', of, the, 'non-additively']), verbo([expressed]), complemento([genes, had, expression, levels, shifted, towards, maternal, levels, of, transcription, and, these, differed, in, the, reciprocal, hybrids])]). relacion([sujeto(['Allelic', expression, analysis, indicated, that, most, genes, with, altered, allelic, contributions, in, the, hybrids, had, an]), verbo([increase]), complemento([in, the, expression, level, of, the, 'hybrid\'s', maternal, allele])]). relacion([sujeto(['We']), verbo([found]), complemento([that, 'miR-34a', expression, was, significantly, downregulated, in, 'HCC', tissues, '(', 'P<0'])]). relacion([sujeto(['Reduced', expression, of, 'miR-34a', was]), verbo([associated]), complemento([with, vascular, 'invasion,', and, advanced, 'TNM', stage, '(', 'P<0'])]). relacion([sujeto(['Kaplan-Meier', revealed, that, reduced, expression, of, 'miR-34a', was]), verbo([associated]), complemento([with, poor, overall, survival, '(', 'log-rank', 'test,', 'P<0'])]). relacion([sujeto(['We']), verbo([found]), complemento([that, 'miR-217', was, downregulated, in, 'HCC', tissues])]). relacion([sujeto(['Kaplan-Meier', analysis, and, 'log-rank', test, showed, that, 'HCC', patients, with, low, expression, of, 'miR-217', was]), verbo([associated]), complemento([with, shorter, overall, survival, than, patients, with, high, expression, '(', 'log-rank', 'test,', 'P<0'])]). relacion([sujeto(['Our', data, showed, that, downregulation, of, 'miR-34a', and, 'miR-217', was]), verbo([associated]), complemento([with, 'HCC', progression, and, both, of, them, may, act, as, tumor, suppressor, in, 'HCC'])]). relacion([sujeto(['Carbon', nanomaterials, themselves, do, not, usually]), verbo([act]), complemento([as, photodynamic, therapy, '(', 'PDT)', agents, owing, to, the, high, 'hydrophobicity,', 'however,', when, the, surface, is, passivated, or, 'functionalized,', these, materials, become, great, vehicles, for, 'PDT'])]). relacion([sujeto(['Moreover,', conjugation, of, carbonaceous, nanomaterials, with, the, photosensitizer, '(', 'PS)', and, relevant]), verbo([targeting]), complemento([ligands, enhances, properties, such, as, 'selectivity,', 'stability,', and, high, quantum, 'yield,', making, them, readily, available, for, versatile, biomedical, applications])]). relacion([sujeto(['While', a, variety, of, established, complications, are]), verbo([associated]), complemento([with, this, 'technique,', most, are, directly, understood, and, treated])]). relacion([sujeto(['Bloody', epiphora, is, a]), verbo([finding]), complemento([with, potentially, ominous, causes])]). relacion([sujeto(['Topoisomerase', 'I', '(', topo, 'I)', is, likely, to, be, one, of, the]), verbo([targets]), complemento([of, these, compounds])]). relacion([sujeto(['Results', of, comet, assays, and, molecular, docking, indicate, that, the, representative, compounds, may]), verbo([act]), complemento([as, topo, 'I', 'poisons,', causing, 'single-strand', 'DNA', damage, by, stabilizing, the, topo, 'I-DNA', cleavage, complex])]). relacion([sujeto(['In', 'particular,', the, most, potent, 'compound,', 1, -, '(', 'butylamino)-3-(3,6-dichloro-9H-carbazol-9-yl)propan-2-ol', '(', 6, ')', ',', was, shown, to, be, able, to]), verbo([induce]), complemento(['G2', -, phase, 'cell-cycle', arrest, and, apoptosis, in, 'HeLa', cells])]). relacion([sujeto(['Drotaverin', also]), verbo([acts]), complemento([as, a, cytostatic, compound, for, several, human, tumor, cell, lines, and, nonmalignant, mouse, 'fibroblasts,', and, 'EC50', values, as, low, as, 3.0, μM, were, observed, in, 'SRB', assays, for, 'HT-29', human, colorectal, carcinoma, cells])]). relacion([sujeto([',', 'aromatization,', benzylic, 'oxidation)']), verbo([led]), complemento([to, a, reduced, activity, or, a, complete, loss, of, cytotoxicity])]). relacion([sujeto(['Staining', of, the, cells, with, acridine, orange, showed, the, cell, membrane, of, the, dead, cells, to, be, still, 'intact,', and, a, slight, 'G1/G0']), verbo([arrest]), complemento([in, the, treated, cells, was, observed, after, 24, h])]). relacion([sujeto(['Extra', annexin, 'V-FITC/PI', assays, and, flow, cytometry, revealed, drotaverine, mainly, to]), verbo([act]), complemento([as, a, cytostatic, and, only, to, a, minor, extent, as, cytotoxic, agent])]). relacion([sujeto(['Filamentous', fungi, are, major, plant, biomass, 'decomposer,', and, capable, of, forming, all, the]), verbo([required]), complemento([enzymes])]). relacion([sujeto(['Here,', we, characterized, the, 'GH10', and, 'GH11', 'endo-xylanases', and, a, 'CE1', 'acetyl-xylan', esterase, '(', 'Axe1)', from, a, superior, 'biomass-degrading', 'strain,', 'Aspergillus', fumigatus, 'Z5,', and, examined, how, they]), verbo([interact]), complemento([in, xylan, degradation])]). relacion([sujeto(['Cellulose-binding', '(', 'CBM1)', domain]), verbo([inhibited]), complemento(['GH10', xylanase, activities, for, pure, 'xylan,', but, afforded, them, an, ability, to, hydrolyze, washed, corncob, particles, '(', 'WCCP)'])]). relacion([sujeto(['In', 'contrast,', 'GH11', xylanases, had, no, 'CBM1,', but, still, could]), verbo([bind]), complemento([xylan, and, hydrolyzed, 'WCCP,', 'however,', no, synergism, displayed, with, 'Axe1'])]). relacion([sujeto(['They', exhibit, different, mechanisms, to]), verbo([bind]), complemento([to, cellulose, and, 'xylan,', and, act, in, synergy, when, these, two, structures, are, intact])]). relacion([sujeto(['Extracted', human, teeth]), verbo([have]), complemento([been, used, to, practice, operative, techniques, for, a, very, long, time])]). relacion([sujeto(['As', a, natural, surrogate, for, a, live, tooth, in, 'vivo,', their, use]), verbo([has]), complemento([traditionally, been, very, important, for, the, development, of, skills, in, trainee, 'dentists,', as, well, as, their, qualified, colleagues, who, wish, to, practice, existing, or, new, skills])]). relacion([sujeto(['As', synthetic, alternatives, develop, greater, 'authenticity,', alongside, a, society, in, which, many]), verbo([retain]), complemento([their, natural, dentition, well, into, old, 'age,', the, current, paradigm, relating, to, how, extracted, teeth, in, dental, education, are, used, needs, to, be, 're-visited'])]). relacion([sujeto(['This', article, will, seek, to, question, whether, there, is, a, legal, or, ethical, requirement, to]), verbo([gain]), complemento([consent, for, the, use, of, extracted, teeth, from, 'patients,', as, well, as, exploring, the, status, of, whether, extracted, dental, tissue, can, be, considered, to, be, the, property, of, either, patient, or, surgeon])]). relacion([sujeto(['We']), verbo([report]), complemento([here, for, the, first, time, the, development, of, adventitious, holdfasts, from, 'Macrocystis', stipes])]). relacion([sujeto(['Within', 4, months, new, thalli]), verbo([increased]), complemento([in, size, and, 'vitality,', and, developed, reproductive, fronds])]). relacion([sujeto(['Our', results]), verbo([suggest]), complemento([the, usage, of, these, structures, for, auxiliary, attachment, techniques])]). relacion([sujeto(['These', could]), verbo([act]), complemento([as, a, 'backup,', when, primary, holdfasts, are, 'weak,', and, thus, improve, the, survival, rate, of, the, giant, kelp, in, natural, beds])]). relacion([sujeto([hospital, industry]), verbo([has]), complemento([recently, witnessed, a, number, of, policy, changes, aimed, at, aligning, hospital, payments, to, costs, and, these, can, be, traced, to, significant, concerns, regarding, selection, of, profitable, patients, and, procedures, by, 'physician-owned', specialty, hospitals])]). relacion([sujeto(['The', policy, responses, to, specialty, hospitals]), verbo([have]), complemento([alternated, between, payment, system, reforms, and, outright, moratoriums, on, hospital, operations, including, one, in, the, recently, enacted, 'Affordable', 'Care', 'Act'])]). relacion([sujeto(['The', current, paper, takes, into, account, heterogeneity, in, specialty, hospital, behavior, and]), verbo([finds]), complemento([some, evidence, of, their, adverse, impact, on, profit, margins, of, competitor, 'hospitals,', especially, 'for-profit', hospitals])]). relacion([sujeto(['Exploiting', a, 'fixed-effects', model, that, relies, on, 'within-county', 'variations,', relative, to, the, corresponding, changes, in, other, 'counties,', 'I']), verbo([find]), complemento([that, while, individuals, are, likely, to, experience, worse, 'self-reported', mental, health, when, local, house, prices, 'decline,', this, association, is, most, pronounced, for, individuals, who, are, least, likely, to, be, homeowners])]). relacion([sujeto(['This']), verbo([finding]), complemento([is, not, consistent, with, a, prediction, from, a, pure, wealth, mechanism, but, rather, with, the, hypothesis, that, house, prices, act, as, an, economic, barometer])]). relacion([sujeto(['The', primary, 'result-that', lower, local, house, prices]), verbo([have]), complemento([adverse, impact, on, 'self-reported', mental, health, of, homeowners, and, 'renters-is', consistent, with, studies, using, data, from, the, 'United', 'Kingdom'])]). relacion([sujeto(['To', investigate, the, ability, of, the, 'proteases,', subtilisin, and, 'α-chymotrypsin', '(', 'aCT),', to]), verbo([inhibit]), complemento([the, adhesion, of, 'Candida', albicans, biofilm, to, a, polypropylene, surface])]). relacion([sujeto(['Extensive', studies, in, model, organisms]), verbo([have]), complemento([unveiled, the, molecular, mechanisms, underpinning, the, 'RNA', silencing, 'phenomena,', and, the, accumulating, knowledge, have, characterized, the, intricate, pathways, and, the, repertoire, of, proteins, responsible, for, the, actions, of, small, 'RNAs', characterized, as, microRNAs, '(', 'miRNAs)', or, small, interfering, 'RNAs', '(', 'siRNAs)'])]). relacion([sujeto(['Although', the, 'single-stranded,', matured, guide, small, 'RNAs', direct, the, effector, ribonucleoprotein, complexes, to]), verbo([induce]), complemento([gene, silencing, in, 'sequence-specific', 'manner,', the, 'double-stranded', 'intermediate,', the, small, 'RNA', 'duplexes,', which, are, processed, as, nascent, products, of, the, 'RNase', 'III', enzyme, 'activities,', act, as, key, to, determine, the, downstream, molecular, pathways, and, the, fate, of, small, 'RNAs'])]). relacion([sujeto(['Since', 2004, 'a single', varicella, vaccination, for, all, infants, aged, 11, -, 14, &, 'nbsp;months']), verbo([has]), complemento([been, recommended, in, 'Germany', and, since, 2009, 'a second', dose, at, the, age, of, 15, -, 23, &, 'nbsp;months', is, recommended])]). relacion([sujeto(['A national', sentinel, system]), verbo([has]), complemento([been, in, place, since, 2005])]). relacion([sujeto(['Sentinel', and, mandatory, notification, data, showed, the, largest]), verbo([decrease]), complemento([among, the, 1, -, 4, &, 'nbsp;year-olds', '(', -, 94, and, -, 90, '%', resp])]). relacion([sujeto(['In', 2014, ',', varicella, incidences]), verbo([increased]), complemento([in, all, age, 'groups,', but, not, the, 'cases/medical-practice/month', by, age, in, the, sentinel])]). relacion([sujeto(['Increasing', vaccination, coverage, and]), verbo([decreasing]), complemento([varicella, cases, demonstrate, the, success, of, routine, childhood, varicella, vaccination])]). relacion([sujeto(['Mandatory', notification, data, allow, incidence, 'calculation;', 'The', sentinel, system]), verbo([has]), complemento([been, providing, more, detailed, information, about, vaccination, 'status,', better, data, quality, and, continuous, national, data, since, 2005, ',', irrespective, of, the, 'Infectious', disease, protection, act])]). relacion([sujeto(['To']), verbo([report]), complemento([the, impact, of, an, inpatient, anticoagulation, stewardship, program, at, a, community, hospital, to, promote, optimal, anticoagulant, use])]). relacion([sujeto(['The', anticoagulation, team, '(', 'ACT)', stewardship, program, consists, of, two, clinical, pharmacists, and, hematologists, to]), verbo([provide]), complemento([oversight, of, 'anticoagulants,', high, cost, reversal, agents, including, prothrombin, complex, concentrate, '(', 'PCC,', 'Kcentra™),', and, 'heparin-induced', thrombocytopenia, '(', 'HIT)', management])]). relacion([sujeto(['Of', the, 'interventions,', 71, '%', were]), verbo([provided]), complemento([to, the, medical, service, and, 22, '%', to, surgical, services, with, acceptance, rates, of, 91, and, 83, '%', ',', respectively])]). relacion([sujeto(['Regarding', 'HIT', 'interventions,', 52, '%', of, interventions]), verbo([involved]), complemento(['pharmacokinetic/pharmacodynamics', optimization, in, 18, patients, with, suspected, or, confirmed, 'HIT'])]). relacion([sujeto(['Arachidonic', acid, is, modified, by, cyclooxygenases, into, active, compounds, called, eicosanoids, that]), verbo([act]), complemento([as, signaling, molecules, in, a, number, of, physiological, processes])]). relacion([sujeto(['Excessive', production, of, eicosanoids]), verbo([leads]), complemento([to, several, pathological, conditions, such, as, inflammation])]). relacion([sujeto(['In', the, present, 'contribution,', molecular, dynamic, analysis, was, performed, to, evaluate, the]), verbo([binding]), complemento([of, 'diclofenac,', 9, -, hydroxy, aristolochic, acid, '(', 9, -, 'HAA)', and, indomethacin, to, 'PLA2'])]). relacion([sujeto(['Furthermore,', analysis, of, intermolecular]), verbo([binding]), complemento([energy, components, indicated, that, hydrophobic, interactions, were, dominant, in, binding, process])]). relacion([sujeto(['On', the, basis, of, obtained, 'data,', inhibitors, bearing, fused, rings, with, hydrogen, 'acceptor/donor', 'substituent(s)']), verbo([interacted]), complemento([with, 'His48', and, 'Asp49', residues, of, the, active, site])]). relacion([sujeto(['Long', 'non-coding', 'RNAs', '(', 'lncRNAs)']), verbo([have]), complemento([been, demonstrated, to, act, as, a, critical, regulator, in, the, processes, of, tumor, biology])]). relacion([sujeto(['High', 'lncRNA-ATB', expression, in, tumor, tissue, was]), verbo([associated]), complemento([with, larger, tumor, 'size,', lymph, node, 'metastasis,', and, distant, metastasis, in, patients, with, 'NSCLC,', respectively])]). relacion([sujeto(['In', vitro, experiments, showed, that, 'down-regulation', of, 'lncRNA-ATB']), verbo([promoted]), complemento([the, cell, 'apoptosis,', whereas, inhibited, the, cell, 'viability,', cell, 'migration,', and, cell, invasion])]). relacion([sujeto(['High', expression, of, 'lncRNA-ATB', indicated, a, poor, prognosis, and]), verbo([led]), complemento([to, the, cell, proliferation, and, metastasis, in, 'NSCLC'])]). relacion([sujeto(['It', was, shown, that, in, the, system, containing, 'carnosine,', iron, ions, and, 'Angeli\'s', 'salt,', a, new, type, of, 'DNICs']), verbo([bound]), complemento([with, carnosine, as, ligand, '{', '(', 'carnosine)2-Fe-(NO)2},', was, formed])]). relacion([sujeto(['Carnosine-bound', 'DNICs', appear, to, be, one, of, the, 'cell\'s', adaptation, mechanisms, when, the, amount, of, reactive, carbonyl, compounds]), verbo([increases]), complemento([at, hyperglycemia])]). relacion([sujeto(['These', complexes, can, also]), verbo([participate]), complemento([in, signal, and, regulatory, ways, of, 'NO', and, can, act, as, protectors, at, oxidative, and, carbonyl, stress, conditions])]). relacion([sujeto(['Human', immunodeficiency, virus, '(', 'HIV)', infection, among, men, who]), verbo([have]), complemento([sex, with, men, '(', 'MSM)', has, increased, to, a, drastic, proportion, throughout, 'India', in, the, last, couple, of, years, due, to, a, lack, of, productive, identification, and, management, framework])]). relacion([sujeto(['In', apprehension, of, social, disgrace, these, men, attempt, to, live, a, normal, hetero, conjugal, life, 'and,', in, the, 'process,']), verbo([act]), complemento([as, a, bridge, in, spreading, the, virus, to, their, women, partners])]). relacion([sujeto(['In', this, case]), verbo([report]), complemento([we, have, highlighted, two, cases, which, clearly, distinguished, the, adequacy, of, 'HIV', treatment, among, 'MSM', when, they, are, diagnosed, during, early, or, late, phases, of, infection])]). relacion([sujeto(['An', intensive, and, ample, counseling, to, comprehend, the, psychology, and, sexual, behavior, of, these, men, was]), verbo([found]), complemento([to, be, critically, important, in, both, the, cases])]). relacion([sujeto(['It', also]), verbo([provides]), complemento([a, format, for, the, medical, practitioners, here, in, managing, and, treating, related, cases])]). relacion([sujeto(['We', investigated, the]), verbo([interacting]), complemento([impacts, of, urban, landscape, and, gardening, practices, on, the, species, richness, and, total, abundance, of, communities, of, common, butterfly, communities, across, 'France,', using, data, from, a, nationwide, monitoring, scheme])]). relacion([sujeto(['We', show, that, urbanization]), verbo([has]), complemento([a, strong, negative, impact, on, butterfly, richness, and, abundance, but, that, at, a, local, 'scale,', such, impact, could, be, mitigated, by, gardening, practices, favoring, nectar, offer])]). relacion([sujeto(['We']), verbo([found]), complemento([few, interactions, among, these, landscape, and, local, scale, 'effects,', indicating, that, 'butterfly-friendly', gardening, practices, are, efficient, whatever, the, level, of, surrounding, urbanization])]). relacion([sujeto(['This', holds, a, strong, message, for, park, managers, and, private, 'gardeners,', as, gardens, may]), verbo([act]), complemento([as, potential, refuge, for, butterflies, when, the, overall, landscape, is, largely, unsuitable])]). relacion([sujeto(['CuAlO2']), verbo([has]), complemento([been, examined, as, a, potential, luminescent, material, by, substituting, 'Eu', for, 'Al', cations, in, the, delafossite, structure])]). relacion([sujeto(['CuAlO2:Eu(3+)', nanofibers]), verbo([have]), complemento([been, prepared, via, electrospinning, for, the, ease, of, mitigating, synthesis, requirements, and, for, future, optoelectronics, and, emerging, applications])]). relacion([sujeto(['Further', electrical, characterization, indicated, that, these, fibers, exhibit, semiconducting, behavior, and, the, introduction, of, 'Eu', could]), verbo([act]), complemento([as, 'band-edge', 'modifiers,', thus, changing, the, thermal, activation, energies])]). relacion([sujeto(['Type', and, levels, of, bitter, sesquiterpene, lactones, '(', 'STLs)']), verbo([participate]), complemento([in, conferring, bitterness, in, vegetables])]). relacion([sujeto(['Comparative', transcriptome, analysis, allowed, the, identification, of, 69, ',', 352, 'SNPs', and, of, 1640, differentially]), verbo([expressed]), complemento([genes, that, maintained, the, pattern, independently, of, the, site])]). relacion([sujeto(['Finally,', 46, genes, encoding, transcription, factors, '(', 'TFs)']), verbo([maintained]), complemento([a, differential, expression, pattern, between, the, two, varieties, regardless, of, the, growth, 'site;', correlation, analyses, among, 'TFs,', 'GAS,', 'GAO', gene, expressions, and, 'STLs', contents, suggest, that, one, 'MYB', and, one, bHLH, may, act, in, the, pathway])]). relacion([sujeto(['Based', on, a, previous]), verbo([report]), complemento([of, a, 'CSP', acting, as, surfactant, in, the, proboscis, of, the, moth, 'Helicoverpa', 'armigera,', we, revealed, the, presence, of, orthologue, proteins, in, two, other, moths, 'Plutella', xylostella, and, 'Chilo', 'suppressalis,', as, well, as, two, butterflies, 'Papilio', machaon, and, 'Pieris', 'rapae,', using, immunodetection, and, proteomic, analysis])]). relacion([sujeto(['This', fact, prompted, us, to, search, for, other, functions, of, these, proteins, and, discovered, that, 'CSPs', are, abundantly]), verbo([expressed]), complemento([in, the, eyes, of, 'H'])]). relacion([sujeto([armigera, and, possibly]), verbo([involved]), complemento([as, carriers, for, carotenoids, and, visual, pigments])]). relacion([sujeto(['We', propose, that, structurally, related, 'CSPs', solubilise, nutritionally, important, carotenoids, in, the, 'proboscis,', while, they]), verbo([act]), complemento([as, carriers, of, both, 'β-carotene', and, its, derived, products, 3, -, hydroxyretinol, and, 3, -, hydroxyretinal, in, the, eye])]). relacion([sujeto(['The', use, of, soluble, olfactory, 'proteins,', such, as, 'CSPs,', as, carriers, for, visual, pigments, in, 'insects,', here]), verbo([reported]), complemento([for, the, first, 'time,', parallels, the, function, of, 'retinol-binding', protein, in, 'vertebrates,', a, lipocalin, structurally, related, to, vertebrate, 'odorant-binding', proteins])]). relacion([sujeto(['Traditionally,', keloids]), verbo([have]), complemento([been, considered, as, a, result, of, aberrant, wound, 'healing,', involving, excessive, fibroblast, participation, that, is, characterized, by, hyalinized, collagen, bundles])]). relacion([sujeto(['However,', the, usefulness, of, this, characterization]), verbo([has]), complemento([been, questioned])]). relacion([sujeto(['In', recent, 'years,', studies]), verbo([have]), complemento([reported, the, appropriate, use, of, verapamil, for, keloids, and, hypertrophic, scars])]). relacion([sujeto(['Verapamil', could]), verbo([act]), complemento([as, an, effective, alternative, modality, in, the, prevention, and, treatment, of, keloid, and, hypertrophic, scars])]). relacion([sujeto(['A', larger, number, of, studies, are]), verbo([required]), complemento([to, confirm, our, conclusion])]). relacion([sujeto(['Previous', research]), verbo([has]), complemento([been, performed, by, administering, these, drugs, as, nanoparticles, that, target, the, ulcerated, intestinal, regions, and, increase, their, bioavailability])]). relacion([sujeto(['It']), verbo([has]), complemento([been, reported, that, silk, fibroin, can, act, as, a, drug, carrier, and, shows, 'anti-inflammatory', properties])]). relacion([sujeto(['This', study, was, designed, to]), verbo([enhance]), complemento([the, interaction, of, the, silk, fibroin, nanoparticles, '(', 'SFNs)', with, the, injured, intestinal, tissue, by, functionalizing, them, with, the, peptide, motif, 'RGD', '(', 'arginine-glycine-aspartic', 'acid)', and, to, evaluate, the, intestinal, 'anti-inflammatory', properties, of, these, 'RGD-functionalized', silk, fibroin, nanoparticles, '(', 'RGD-SFNs)', in, the, trinitrobenzenesulfonic, acid, '(', 'TNBS)', model, of, rat, colitis])]). relacion([sujeto(['However,', both, treatments, improved, the, intestinal, wall, integrity, by]), verbo([increasing]), complemento([the, gene, expression, of, some, of, its, markers, '(', trefoil, 'factor-3', and, 'mucins)'])]). relacion([sujeto(['On', 'necropsy,', intestine, of, rats, was]), verbo([found]), complemento([infected, with, adult, cestode, parasites, of, 'Hymenolepis', diminuta, and, 'H'])]). relacion([sujeto(['Liver', was]), verbo([found]), complemento([infected, with, 'Capillaria', hepatica, and, 'Cysticercus', fasciolaris])]). relacion([sujeto(['In', 'overall,', 68.67, &, 'nbsp;%', rats, were]), verbo([found]), complemento([infected, of, which, 59.65, &, 'nbsp;%', were, infected, with, nematode, 'parasite,', 'C'])]). relacion([sujeto([bengalensis, may]), verbo([act]), complemento([as, an, important, source, of, zoonotic, infections, and, thus, direct, or, indirect, contact, with, excrements, and, carcasses, of, this, rodent, 'species,', should, be, avoided])]). relacion([sujeto(['Gastrointestinal', parasites, are, among, the, most, common, parasitic, infections]), verbo([found]), complemento([in, stray, 'cats,', which, might, act, potential, helminthic, parasites, to, domestic, cats])]). relacion([sujeto(['The', prevalence, of, parasites]), verbo([found]), complemento(['were:', 'Taenia', taeniaeformis, '(', 60, &, 'nbsp;%),', 'Dipylidium', caninum, '(', 58, &, 'nbsp;%),', 'Taenia', hydatigera, '(', 24, &, 'nbsp;%),', 'Mesocestoides', lineatus, '(', 78, &, 'nbsp;%),', 'Ancylostoma', tubaeforme, '(', 14, &, 'nbsp;%),', 'Toxascaris', leonina, '(', 30, &, 'nbsp;%),', 'Toxocara', cati, '(', 78, &, 'nbsp;%),', 'Physaloptera', praeputialis, '(', 10, &, 'nbsp;%),', and, 'Syphacia', obvelata, '(', 10, &, 'nbsp;%)'])]). relacion([sujeto(['Here,', we, review, studies, that, collectively]), verbo([suggest]), complemento([that, sodium, deficit, recruits, the, mesolimbic, system, to, play, a, role, in, the, behavioral, expression, of, sodium, appetite])]). relacion([sujeto(['Some', of, the, hormones, that, are]), verbo([released]), complemento([in, response, to, sodium, deficit, act, directly, on, both, dopamine, and, nucleus, accumbens, elements])]). relacion([sujeto(['Strenuous', exercise, is, followed, by, an, elevation, of, many, cytokines, with, inflammation]), verbo([regulating]), complemento([properties])]). relacion([sujeto(['Since', most, cytokines]), verbo([act]), complemento([at, 'pico-', or, nanomolar, concentrations, many, investigations, failed, to, detect, their, concentrations, in, vivo])]). relacion([sujeto(['Hence,', the, aim, of, this, study, was, to, evaluate, the, significance, of, cytokine, measurements, '(', 'IL-1β,', 'TNF-α,', 'IL-1ra,', 'IL-6,', 'CCL2', and, 'CXCL8)', in, a]), verbo([stimulated]), complemento(['whole-blood', culture, '(', 'sWBC)', compared, to, serum, with, respect, to, their, 'exercise-induced', kinetics, and, detection, rates])]). relacion([sujeto(['While', exercise, did, not, affect, 'pro-inflammatory', cytokines, in, 'serum,', in, sWBC, only, 'IL-1β', was]), verbo([increased]), complemento([1.2, -, fold, at, 3, h, '(', 'p<0,05)'])]). relacion([sujeto(['All', other, cytokines]), verbo([increased]), complemento([both, in, sWBC, and, serum])]). relacion([sujeto(['Both', approaches]), verbo([provide]), complemento([a, synergistic, insight, into, inflammatory, processes, on, the, cytokine, level])]). relacion([sujeto(['Joseph', estuaries, '(']), verbo([targeted]), complemento(['RESTORE', 'sites)', in, 'Northwest', 'Florida'])]). relacion([sujeto(['There', are, 44, ',', 789, ',', 18, ',', 456, ',', and, 12, ',', 897, clinical, trials, registered, to, evaluate, '(', 1, ')', drug, delivery, 'technology,', '(', 2, ')', biomolecule, 'platform,', and, '(', 3, ')', drug, metabolism, and, 'pharmacokinetic-pharmacodynamic', 'interactions;', representing, 19, '%', -, 60, '%']), verbo([increase]), complemento([over, the, last, 3, years])]). relacion([sujeto(['In', 'November', 2005, ',', hepatitis, 'A', vaccine, was, funded, under, the, 'Australian', 'National', 'Immunisation', 'Program', for, 'Aboriginal', and, 'Torres', 'Strait', 'Islander', '(', 'Indigenous)', children, aged, 12, -, 24, months, in, the]), verbo([targeted]), complemento([jurisdictions, of, 'Queensland,', 'South', 'Australia,', 'Western', 'Australia', and, the, 'Northern', 'Territory'])]). relacion([sujeto(['Notification', and, hospitalisation, rates, in, 'Indigenous', children, aged, &, 'lt;5years', from]), verbo([targeted]), complemento([jurisdictions, declined, in, the, 'post-vaccine', period, when, compared, to, the, 'pre-vaccine', period, '(', 'notifications:', 'IRR=0'])]). relacion([sujeto([6, ;, 95, '%', 'CI', 0.02, -, 0.15, ')', in]), verbo([targeted]), complemento([jurisdictions])]). relacion([sujeto(['For', 'non-Indigenous', people, from]), verbo([targeted]), complemento(['jurisdictions,', notification, rates, decreased, significantly, in, children, aged, &, 'lt;5years', '(', 'IRR', 0.47, ;, 95, '%', 'CI', 0.31, -, 0.71, ')', ',', and, significantly, more, overall, '(', 'IRR=0'])]). relacion([sujeto(['The', national, hepatitis, 'A', immunisation, program]), verbo([has]), complemento([had, a, significant, impact, in, the, targeted, population, with, relatively, modest, vaccine, 'coverage,', with, evidence, suggestive, of, substantial, herd, protection, effects])]). relacion([sujeto(['To', investigate, whether, clinical, or, laboratory, variables, on, admission, of, patients, with, odontogenic, infections, are]), verbo([associated]), complemento([with, a, severe, clinical, course, and, a, prolonged, hospital, 'stay,', we, hypothesised, that, specific, factors, such, as, the, serum, concentration, of, 'C-reactive', protein, '(', 'CRP)', may, act, as, predictors, of, the, duration, of, stay])]). relacion([sujeto(['We']), verbo([found]), complemento([that, the, concentration, of, 'CRP', was, a, significant, predictor, of, hospital, stay, '(', 'p=0'])]). relacion([sujeto(['Recent', studies, based, on, biography, analysis]), verbo([provide]), complemento([support, for, the, notion, that, the, prevalence, of, mental, illness, in, the, creative, geniuses, of, 'art,', literature, and, science, is, higher, than, it, is, in, more, ordinary, folk])]). relacion([sujeto(['However,', this, relationship, between, madness, and, 'genius,', which, was, also, addressed, by, the, classical, 'philosophers,']), verbo([has]), complemento([been, generalized, to, all, branches, of, professional, endeavour])]). relacion([sujeto(['Whilst', it, may, hold, true, for, illustrious, personalities, of, the, fine, 'arts,', we]), verbo([found]), complemento([that, the, relationship, proves, inappropriate, to, the, biographies, of, ten, individuals, renowned, in, history, for, their, innovative, contributions, to, medical, science])]). relacion([sujeto(['Furthermore,', examination, of, these, ten, biographies, invites, the, hypothesis, that, certain, personality, traits, -, 'especially,', 'agreeableness,', conscientiousness, and, openness, to, new, experience, -, can]), verbo([act]), complemento([to, enhance, creativity, and, protect, against, mental, illness])]). relacion([sujeto(['Excessive', dermal, scarring, '(', 'EDS)', is, a, wound, healing, 'complication,', characterized, by, protruded, erythematous, and, inelastic, '\'', proliferative, scar, 'tissue\'', which, is]), verbo([associated]), complemento([with, increased, and, prolonged, inflammation, process, within, the, wound, microenvironment])]). relacion([sujeto([&, 'quot;Subphysiological', 'cold"']), verbo([has]), complemento([been, administered, for, its, antiinflammatory, effects, which, act, via, decreasing, vascular, permeability, and, downregulating, proliferation, of, cells, in, the, wound, 'environment;', this, knowledge, supports, our, hypothesis, that, &, 'quot;subphysiological', cold, 'application"', can, also, be, utilized, in, human, 'EDS', prophylaxis, and, treatment])]). relacion([sujeto(['In', this, 'study,', we, are, reviewing, the, mechanisms, of, its, both, deleterious, and, therapeutic, actions, and]), verbo([suggesting]), complemento([another, possible, application, for, prevention, 'and/or', treatment, of, human, 'EDS', conditions])]). relacion([sujeto(['The', treatment, and, prevention, of, migraine, within, the, last, decade]), verbo([has]), complemento([become, largely, pharmacological])]). relacion([sujeto(['triptans)']), verbo([has]), complemento([helped, many, migraine, sufferers, to, lead, a, normal, 'life,', there, is, still, little, knowledge, with, respect, to, the, factors, responsible, for, precipitating, a, migraine, attack])]). relacion([sujeto(['Evidence', from, biochemical, and, behavioural, studies, from, a, number, of, disciplines, is, integrated, to, put, forward, the, proposal, that, migraine, is, part, of, a, cascade, of, 'events,', which, together]), verbo([act]), complemento([to, protect, the, organism, when, confronted, by, a, metabolic, challenge])]). relacion([sujeto(['Transgenic', 'cotton,']), verbo([expressing]), complemento([a, single, 'Bt', 'toxin,', was, first, used, in, the, 1990, s, to, control, 'H'])]). relacion([sujeto(['Landscape', scale, or, greater, pest, suppression]), verbo([has]), complemento([been, reported, in, some, countries, using, this, technology])]). relacion([sujeto(['This', response, can, be, 'attributed,', at, least, in, 'part,', to, '(', 1, ')', a, precautionary, cap, '(', 30, '%', of, total, cotton, 'grown,', by, 'area)', being, applied, to, 'Ingard®', to, restrict, the, development, of, 'Bt', resistance, in, the, 'pest,', and, '(', 2, ')', during, the, 'Ingard®', 'era,', cotton, production, greatly]), verbo([increased]), complemento(['(', as, did, that, of, another, host, 'plant,', 'sorghum)', and, 'H'])]). relacion([sujeto([armigera, '(', in, particular, the, 3, rd, and, older, 'generations)']), verbo([responded]), complemento([in, concert, with, this, increase, in, host, plant, availability])]). relacion([sujeto([armigera, failed, to, track]), verbo([increased]), complemento(['host-plant', supply, and, moth, numbers, decreased])]). relacion([sujeto(['Greater', toxicity, of, the, two, gene, 'product,', introduction, of, no, cap, on, 'Bt', cotton, 'proportion,', and, an]), verbo([increase]), complemento([in, natural, enemy, abundance, are, suggested, as, the, most, likely, mechanisms, responsible, for, the, suppression, observed])]). relacion([sujeto(['Hepatic', macrophages, '(', 'hMø)']), verbo([have]), complemento([a, pivotal, role, in, liver, 'fibrosis,', being, able, to, act, in, both, its, promotion, and, its, resolution])]). relacion([sujeto(['It', is, 'well-known', that, mesenchymal, stromal, cells, '(', 'MSCs)', can]), verbo([modulate]), complemento([the, 'immune/inflammatory', cells])]). relacion([sujeto(['We', previously, described, evidence, of, the, antifibrotic, effects, of, in, vivo, applying, 'MSCs,', which, were]), verbo([enhanced]), complemento([by, forced, overexpression, of, 'insulin-like', growth, factor, 1, '(', 'AdIGF-I-MSCs)'])]). relacion([sujeto(['Fibrosis', was]), verbo([induced]), complemento([in, 'BALB/c', mice, by, chronic, administration, of, thioacetamide, '(', 8, &, 'nbsp;weeks)'])]). relacion([sujeto(['This', group, showed, a, significant, upregulation, in, the, expression, of, 'arginase-1', and, a, higher, downregulation, of, iNOS, expression, thus]), verbo([suggesting]), complemento([decreased, levels, of, oxidative, stress])]). relacion([sujeto(['An', upregulation, in, 'IGF-I', and, 'HGF', expression, was, observed, in, hMø, from, 'AdIGF-I-MSCs-treated', mice]), verbo([suggesting]), complemento([a, restorative, phenotype, in, these, cells])]). relacion([sujeto(['Factors', secreted, by, 'hMø,', preconditioned, with, 'MSCs', 'supernatant,']), verbo([caused]), complemento([a, reduction, in, the, expression, levels, of, hepatic, stellate, cells, 'pro-fibrogenic', and, activation, markers])]). relacion([sujeto(['Moreover,', depletion, of, hMø, abrogated, such, effects, on, the, expression, of, the, most, highly]), verbo([regulated]), complemento([genes])]). relacion([sujeto(['Our', results, indicate, that, 'AdIGF-I-MSCs', are, able, to]), verbo([induce]), complemento([a, 'pro-fibrotic', to, resolutive, phenotype, shift, on, hepatic, 'macrophages,', which, is, a, key, early, event, driving, liver, fibrosis, amelioration])]). relacion([sujeto(['Prenatal', diagnosis]), verbo([involves]), complemento([methods, used, in, early, pregnancy, as, either, screening, tests, or, diagnostic, methods])]). relacion([sujeto(['Further,', university, educational, level, in, relation, to, lower, educational, level, was]), verbo([associated]), complemento([with, an, increased, likelihood, of, undergoing, 'CUB', '(', 'OR', 2.3, ',', 95, '%', 'CI', 2.26, -, 2.35, ')', ',', 'AC', '(', 'OR', 1.54, ',', 95, '%', 'CI', 1.46, -, 1.63, ')', and, 'CVS', '(', 'OR', 2.68, ',', 95, '%', 'CI', 2.44, -, 2.93, ')'])]). relacion([sujeto(['Plant', allelochemicals]), verbo([act]), complemento([as, 'toxins,', inhibitors, of, 'digestion,', and, deterrents, that, affect, the, fecundity, of, insects])]). relacion([sujeto(['These', compounds]), verbo([have]), complemento([attracted, significant, research, attention, in, recent, 'decades,', and, much, is, known, about, the, effects, of, these, xenobiotic, plant, secondary, metabolites, on, insect, development])]). relacion([sujeto(['To', 'date,', although, ecological, interactions, between, xenobiotic, plant, secondary, chemicals, that, retard, insect, growth]), verbo([have]), complemento([been, observed, in, many, 'species,', it, remains, unclear, how, particular, allelochemicals, influence, insect, development, in, a, life, 'stage-dependent', manner])]). relacion([sujeto(['We']), verbo([found]), complemento([that, 2, -, tridecanone, can, affect, insect, 'development;', this, effect, appears, similar, to, the, symptoms, induced, by, the, physiological, imbalance, between, juvenile, and, molting, hormones, in, cotton, bollworm])]). relacion([sujeto(['We', later, detected, that, a]), verbo([decrease]), complemento([in, the, concentration, of, 20, -, hydroxyecdysone, occurred, alongside, the, observed, symptoms])]). relacion([sujeto(['The', expression, of, 'CYP314A1,', 'CYP315A1,', 'CYP18A1,', 'CYP307A1,', and, 'CYP306A1', '(', unigenes, 16487, ',', 15409, ',', 40026, ',', 41217, ',', 35643, ',', 16953, ',', 8199, ',', 13311, ',', and, 13036, ')', were]), verbo([found]), complemento([to, be, induced, by, 2, -, 'tridecanone;', these, are, known, to, be, related, to, the, biosynthesis, or, metabolism, of, 20, -, hydroxyecdysone])]). relacion([sujeto(['Expression', analysis, and, 'RNA', interference, studies, established, that, the, retardant, effect, of, 2, -, tridecanone, on, the, development, of, cotton, bollworm, is]), verbo([mediated]), complemento([by, 'P450', genes])]). relacion([sujeto(['Impaired', iron, homeostasis]), verbo([has]), complemento([been, implicated, in, loss, of, function, in, several, enzymes, requiring, iron, as, a, 'cofactor,', formation, of, toxic, oxidative, 'species,', inflammation, and, elevated, production, of, 'beta-amyloid', proteins])]). relacion([sujeto(['Proteins', secreted, by, 'Treponema', can]), verbo([act]), complemento([directly, on, iron, 'metabolism,', with, hemin, binding, ability, '(', 'HbpA', and, 'HbpB)', and, iron, reductase, able, to, reduce, the, central, ferric, iron, of, 'hemin,', 'iron-containing', proteins, '(', 'rubredoxin,', 'neelaredoxin,', desulfoferrodoxin, 'metalloproteins,', bacterioferritins, 'etc)'])]). relacion([sujeto(['Treponema', can, also]), verbo([interact]), complemento([with, cellular, 'compounds,', especially, plasma, proteins, involved, in, iron, 'metabolism,', contributing, to, the, virulence, of, the, syphilis, spirochetes, '(', e])]). relacion([sujeto(['Association', between, 'Treponema', and, iron]), verbo([binding]), complemento([proteins, results, in, iron, accumulation, and, sequestration, by, 'Treponema', from, host, macromolecules, during, systemic, and, mucosal, infections])]). relacion([sujeto(['In', this, 'paper,', a, novel, foaming, methodology, consisting, of, turbulent, mixing, and, thermally]), verbo([induced]), complemento([phase, separation, '(', 'TIPS)', was, used, to, generate, scaffolds, for, tissue, engineering])]). relacion([sujeto(['The', air, bubbles, entrained, in, the, foam]), verbo([act]), complemento([as, a, template, for, the, macroporous, architecture, of, the, final, scaffolds])]). relacion([sujeto(['Wet', foams, were, crosslinked, via, glutaraldehyde, and, frozen, at, -, 20, &, 'nbsp;°C', to]), verbo([induce]), complemento(['TIPS', in, order, to, limit, film, 'drainage,', bubble, coalescence, and, 'Ostwald', ripening])]). relacion([sujeto([',', a, tendency, to]), verbo([act]), complemento([rashly, in, response, to, heightened, 'affect)', may, be, especially, vulnerable, to, heavy, drinking])]). relacion([sujeto(['Although', naltrexone, treatment, reduced, drinking, 'overall,', young, adults, with, higher, trait, urgency, were, still, at]), verbo([increased]), complemento([risk, for, hazardous, drinking, following, times, of, strong, positive, or, negative, mood])]). relacion([sujeto(['Though', only, occurring, 'rarely,', synergistic, interactions, between, chemicals, in, mixtures]), verbo([have]), complemento([long, been, a, point, of, focus])]). relacion([sujeto(['The', aim, of, the, present, study, is, to, determine, the, threshold, concentration, below, which, proven, synergists, cease, to]), verbo([act]), complemento([as, synergists, towards, the, aquatic, crustacean, 'Daphnia', magna])]). relacion([sujeto(['Synergy', was, defined, as, occuring, in, mixtures, where, either, 'EC50', values]), verbo([decreased]), complemento([more, than, 'two-fold', below, what, was, predicted, by, concentration, addition, '(', horizontal, 'assessment)', or, as, mixtures, where, the, fraction, of, immobile, organisms, increased, more, than, 'two-fold', above, what, was, predicted, by, independent, action, '(', vertical, 'assessment)'])]). relacion([sujeto(['The', lower, threshold, 'concentration,', 'however,']), verbo([decreased]), complemento([with, increasing, test, duration, from, 0.026, '±0'])]). relacion([sujeto(['Testing', synergy, in, relation, to, concentration, addition]), verbo([provided]), complemento([the, most, conservative, values])]). relacion([sujeto(['The', results, emphasize, the, importance, of, test, duration, when, assessing, 'synergy,', but, also, show, that, azole, concentrations, within, the, typically, monitored, range, of, up, to, 0.5, 'μgL(-1)', are, not, likely, to]), verbo([cause]), complemento([severe, synergy, concerning, 'Daphnia', magna, immobilization])]). relacion([sujeto(['After', passage, of, the, 'SMART', 'Act,', emergency, department, visits]), verbo([increased]), complemento([48, '%', ',', surgical, intervention, increased, 100, '%', ',', and, hospital, admission, days, increased, 128, '%'])]). relacion([sujeto(['Patients', were, more, likely, to]), verbo([have]), complemento([an, 'OMS', consult, '(', odds, ratio, '[', 'OR] =', 1.42, ;, 95, '%', confidence, interval, '[', 'CI],', 1.11, -, 1.81, ')', ',', an, incision, and, drainage, '(', 'OR =', 1.48, ;, 95, '%', 'CI,', 1.13, -, 1.94, ')', ',', and, a, longer, hospital, admission, '(', 'P ='])]). relacion([sujeto(['The', average, cost, per, encounter]), verbo([increased]), complemento([by, 20, '%', and, the, total, cost, of, care, increased, by, '$1'])]). relacion([sujeto(['After', limitation, of, dental, 'benefits,', there, was, an]), verbo([increase]), complemento([in, the, volume, and, severity, of, odontogenic, infections])]). relacion([sujeto(['The', negative, public, health, effects, and]), verbo([increased]), complemento([economic, impact, of, eliminating, basic, dental, care, show, the, importance, of, affordable, and, accessible, preventative, oral, health, care])]). relacion([sujeto(['Recent', media]), verbo([reports]), complemento([have, drawn, widespread, attention, to, the, experiences, of, patients, who, are, denied, reproductive, services, at, 'Catholic', hospitals])]). relacion([sujeto(['For', some, 'patients,', such, as, those, experiencing, 'miscarriage,', denial, of, appropriate, treatment, can]), verbo([lead]), complemento([to, serious, health, consequences])]). relacion([sujeto(['There', are, currently, no, federal, or, state, laws]), verbo([requiring]), complemento([health, care, institutions, to, inform, patients, directly, of, the, full, scope, of, medical, services, they, are, unable, to, provide, on, the, basis, of, religion, or, conscience])]). relacion([sujeto(['Inducing', apoptosis, is, an, interesting, therapeutic, approach, to, develop, drugs, that]), verbo([act]), complemento([against, helminthic, parasites])]). relacion([sujeto(['Researchers']), verbo([have]), complemento([investigated, how, curcumin, '(', 'CUR),', a, biologically, active, compound, extracted, from, rhizomes, of, 'Curcuma', 'longa,', affects, 'Schistosoma', mansoni, and, several, cancer, cell, lines])]). relacion([sujeto(['CUR']), verbo([decreased]), complemento([the, viability, of, adult, worms, and, killed, them])]). relacion([sujeto(['CUR']), verbo([induced]), complemento(['DNA', damage, and, fragmentation, and, increased, the, expression, of, 'SmCASP3/7', transcripts, and, the, activity, of, 'Caspase', 3, in, female, and, male, worms])]). relacion([sujeto(['In', a, 2011, 'report,', 'The', 'Future', of, 'Nursing:', 'Leading', 'Change,', 'Advancing', 'Health,', the, 'Institute', of, 'Medicine', examined, the, ways, nurses, could, more, fully, apply, their, knowledge, of, direct, patient, care, to, address, the]), verbo([increasing]), complemento([demands, placed, on, the, health, care, system, since, the, passage, of, the, 'Affordable', 'Care', 'Act'])]). relacion([sujeto(['The']), verbo([report]), complemento(['asked:', &, 'quot;What', roles, can, nursing, assume, to, address, the, increasing, demand, for, 'safe,', 'high-quality,', and, effective, health, care, 'services?"Multiple', variables, influence, a, 'nurse\'s', ability, to, assume, a, leadership, 'role,', and, multiple, barriers, to, these, roles, continue, to, exist])]). relacion([sujeto(['This', article, uses, the, 'first-person', voice, to, share, the, experience, of, a, new, graduate, nurse, in, a, formal, nurse, residency, program, who]), verbo([found]), complemento([himself, in, a, position, to, identify, the, need, 'for,', advocate, 'for,', and, ultimately, influence, a, policy, change, in, the, staffing, practice, of, floating, as, it, was, applied, to, new, 'RNs', on, his, unit])]). relacion([sujeto(['In', a, retrospective, analysis, of, the, 'process,', the, new, graduate, 'RN', and, his, former, professor]), verbo([acting]), complemento([as, a, writing, mentor, developed, a, leadership, framework, for, nurses, called, 'RN', 'LEADER,', which, they, hope, will, empower, and, guide, other, nurses, to, lead, 'evidence-based', change, in, their, workplaces])]). relacion([sujeto(['However,', systematic, reviews]), verbo([suggest]), complemento([that, 'Carotid', 'Revascularization', 'Endarterectomy', 'Versus', 'Stenting', 'Trial/ACT-1', results, may, not, be, generalizable, into, routine, practice])]). relacion([sujeto(['In', 'parallel,', 'meta-analyses']), verbo([suggest]), complemento([that, stroke, rates, on, medical, therapy, may, be, 'declining,', suggesting, that, 'Asymptomatic', 'Carotid', 'Atherosclerosis', 'Study/Asymptomatic', 'Carotid', 'Surgery', 'Trial', 'data,', which, have, underpinned, every, practice, guideline, since, 1995, ',', are, too, historical, for, use, in, 2017])]). relacion([sujeto(['A', recent, review, 'has,', 'however,', identified, a, number, of, 'clinical/imaging', features, that, may, be]), verbo([associated]), complemento([with, higher, rates, of, stroke, on, medical, therapy])]). relacion([sujeto(['In', the, 'interim,', it, would, be, preferable, to]), verbo([target]), complemento([interventions, into, a, smaller, cohort, who, present, with, 'clinical/imaging', features, that, might, render, them, '\'', higher, risk, for, 'stroke\'', on, medical, therapy])]). relacion([sujeto(['We']), verbo([report]), complemento([methyl, ammonium, lead, iodide, '(', 'MAPbI3)', solar, cells, with, an, 'ultra-porous', 'TiO2', electron, transport, layer, fabricated, using, sequential, flame, aerosol, and, atomic, layer, depositions, of, porous, and, compact, 'TiO2', layers])]). relacion([sujeto(['This', demonstrates, that, 'MAPbI3', solar, cells, with, a, 'flame-made', porous, 'TiO2', layer, can]), verbo([have]), complemento([a, comparable, efficiency, to, that, of, the, control, 'MAPbI3', solar, cell, with, the, 'well-established', 'spin-coated', porous, 'TiO2', layer])]). relacion([sujeto(['The', combination, of, flame, aerosol, and, atomic, layer, deposition]), verbo([provides]), complemento([precise, control, of, the, 'TiO2', porosity])]). relacion([sujeto(['The', effects, of, the]), verbo([decrease]), complemento([in, porosity, on, the, device, performance, are, discussed])]). relacion([sujeto(['In', this, 'work,', evidence, that, 'GlnR', is, also, directly]), verbo([involved]), complemento([in, the, regulation, of, antibiotic, biosynthesis, is, provided])]). relacion([sujeto(['In', the, model, strain, 'Streptomyces', coelicolor, 'M145,', an, 'in-frame', deletion, of, glnR, resulted, in, markedly]), verbo([increased]), complemento([actinorhodin, '(', 'ACT)', production, but, reduced, undecylprodigiosin, '(', 'RED)', biosynthesis, when, exposed, to, 'R2YE', culture, medium])]). relacion([sujeto(['Transcriptional', analysis, coupled, with, 'DNA-binding', studies, revealed, that, 'GlnR', represses, 'ACT', but]), verbo([activates]), complemento(['RED', production, directly, via, the, 'pathway-specific', activator, genes, 'actII-ORF4', and, 'redZ,', respectively])]). relacion([sujeto(['The', precise, 'GlnR-binding', sites, upstream, of, these, two]), verbo([target]), complemento([genes, were, defined])]). relacion([sujeto(['We']), verbo([found]), complemento([that, 'S'])]). relacion([sujeto([avermitilis, 'GlnR', '(', 'GlnRsav)', could]), verbo([stimulate]), complemento([avermectin, but, repress, oligomycin, production, directly, through, the, respective, 'pathway-specific', activator, 'genes,', aveR, and, 'olmRI/RII'])]). relacion([sujeto(['To', the, best, of, our, 'knowledge,', this]), verbo([report]), complemento([describes, the, first, experimental, evidence, demonstrating, that, 'GlnR', regulates, antibiotic, biosynthesis, directly, through, 'pathway-specific', regulators, in, 'Streptomyces'])]). relacion([sujeto(['Our', results]), verbo([suggest]), complemento([that, 'GlnR-mediated', regulation, of, antibiotic, biosynthesis, is, likely, to, be, universal, in, streptomycetes])]). relacion([sujeto(['(', -, ')', -, 'Englerin', 'A', '(', '(', -, ')', -, 'EA)']), verbo([has]), complemento([a, rapid, and, potent, cytotoxic, effect, on, several, types, of, cancer, cell, that, is, mediated, by, plasma, membrane, ion, channels, containing, 'Transient', 'Receptor', 'Potential', 'Canonical', 4, protein, '(', 'TRPC4)'])]). relacion([sujeto(['Here', we, show, that, this, is, not, the, case, and, that, the, effect, of, '(', -, ')', -, 'EA', is]), verbo([mediated]), complemento([by, a, heteromer, of, 'TRPC4', and, 'TRPC1', proteins])]). relacion([sujeto(['Both', 'TRPC4', and, 'TRPC1', were]), verbo([required]), complemento([for, '(', -, ')', -, 'EA', 'cytotoxicity,', 'however,', although, 'TRPC4', was, necessary, for, the, '(', -, ')', -, 'EA-evoked', 'Ca2+-elevation,', 'TRPC1', was, not])]). relacion([sujeto(['We', therefore, hypothesized, that, 'Na+/K+-ATPase', might]), verbo([act]), complemento([protectively, by, counteracting, the, 'Na+', load, resulting, from, sustained, 'Na+', entry])]). relacion([sujeto(['Indeed,', inhibition, of, 'Na+/K+-ATPase', by, ouabain, potently, and, strongly]), verbo([increased]), complemento(['(', -, ')', -, 'EA-evoked', cytotoxicity])]). relacion([sujeto(['The', data]), verbo([suggest]), complemento([that, '(', -, ')', -, 'EA', achieves, cancer, cell, cytotoxicity, by, inducing, sustained, 'Na+', entry, through, heteromeric, 'TRPC1/TRPC4', channels, and, that, the, cytotoxic, effect, of, '(', -, ')', -, 'EA', can, be, potentiated, by, 'Na+/K+-ATPase', inhibition])]). relacion([sujeto(['Ab', initio, 'MP2/aug\'-cc-pVTZ', calculations]), verbo([have]), complemento([been, carried, out, to, investigate, hydrogen, 'bonding,', halogen, 'bonding,', and, pnicogen, bonding, involving, tetrahedral, 'P4', and, the, 'FH,', 'ClH,', and, 'FCl', molecules])]). relacion([sujeto(['P4']), verbo([has]), complemento([three, unique, interaction, 'sites:', at, a, vertex, '(', designated, the, 'P1', 'atom);', at, an, edge, '(', the, 'P2-P3', 'bond);', and, at, the, 'P2-P3-P4', face])]). relacion([sujeto(['The', uniqueness, of, molecular, 'P4', is, its, ability, to]), verbo([act]), complemento([as, an, electron, donor, and, an, electron, acceptor, at, the, same, 'site,', except, for, the, 'P2-P3', 'bond,', which, is, only, an, electron, donor])]). relacion([sujeto(['The', type, of, complex, formed, and, its]), verbo([binding]), complemento([energy, depend, on, both, the, interaction, site, of, molecular, 'P4', and, the, interacting, molecule])]). relacion([sujeto(['For', all, complexes, with, 'FH,', 'ClH,', and, 'FCl,', the]), verbo([binding]), complemento([energies, at, a, given, site, with, the, 'P4', molecule, acting, as, the, base, are, greater, than, the, binding, energies, when, 'P4', is, the, acid])]). relacion([sujeto(['Charge-transfer', interactions, and, 'EOM-CCSD', 'spin-spin', coupling, constants, across, 'hydrogen,', 'halogen,', and, pnicogen, bonds, are]), verbo([reported]), complemento([for, all, of, the, 'P4', complexes])]). relacion([sujeto(['Relative', to, '(', 1, ')', 'J(Pi-Pj)', in, molecular, 'P4,', '(', 1, ')', 'J(P1-P2)', coupling, constants]), verbo([decrease]), complemento([in, absolute, value, and, '(', 1, ')', 'J(P2-P3)', coupling, constants, increase, in, 'pnicogen-bonded', complexes, and, the, complex, with, 'FCl', that, has, a, 'PF', halogen, bond])]). relacion([sujeto(['Absolute', values, of, '(', 1, ')', 'J(P1-P2)']), verbo([increase]), complemento([and, those, of, '(', 1, ')', 'J(P2-P3)', decrease, in, 'hydrogen-bonded', complexes, and, complexes, with, 'PCl', halogen, bonds])]). relacion([sujeto(['The', network, structure, of, biological, systems]), verbo([suggests]), complemento([that, effective, therapeutic, intervention, may, require, combinations, of, agents, that, act, synergistically])]). relacion([sujeto(['However,', a, dearth, of, systematic, chemical, combination, datasets]), verbo([have]), complemento([limited, the, development, of, predictive, algorithms, for, chemical, synergism])]). relacion([sujeto(['Here,', we]), verbo([report]), complemento([two, large, datasets, of, linked, 'chemical-genetic', and, 'chemical-chemical', interactions, in, the, budding, yeast, 'Saccharomyces', cerevisiae])]). relacion([sujeto(['NK', cells]), verbo([express]), complemento(['NKG2D,', an, activating, receptor, that, directly, recognizes, 'NKG2D', ligands])]). relacion([sujeto(['These', are]), verbo([expressed]), complemento([at, low, level, on, healthy, 'cells,', but, are, induced, by, stresses, like, infection, and, transformation])]). relacion([sujeto(['We', demonstrate, that, 'RAE-1', is, transcriptionally, repressed, by, histone, deacetylase, inhibitor, 3, '(', 'HDAC3)', in, healthy, 'cells,', and, m18, relieves, this, repression, by, directly]), verbo([interacting]), complemento([with, 'Casein', 'Kinase', 'II', and, preventing, it, from, activating, 'HDAC3'])]). relacion([sujeto(['Accordingly,', we]), verbo([found]), complemento([that, 'HDAC', inhibiting, proteins, from, human, herpesviruses, induce, human, 'NKG2D', ligand, 'ULBP-1'])]). relacion([sujeto(['Thus', our, findings, indicate, that, virally]), verbo([mediated]), complemento(['HDAC', inhibition, can, act, as, a, signal, for, the, host, to, activate, 'NK-cell', recognition])]). relacion([sujeto(['Nucleolin,', a, multifunctional, protein, distributed, in, the, 'nucleolus,']), verbo([participates]), complemento([in, many, modulations, including, rDNA, 'transcription,', 'RNA', 'metabolism,', and, ribosome, assembly])]). relacion([sujeto(['Nucleolin', is, also]), verbo([found]), complemento([in, the, cytoplasm, and, on, the, cell, 'membrane,', and, surface, nucleolin, can, bind, to, various, ligands, to, affect, many, physiological, functions])]). relacion([sujeto(['The', expression, and, localization, of, nucleolin, is, often, abnormal, in, 'cancers,', as, the, differential, distribution, of, nucleolin, in, cancer, can, influence, the, 'carcinogenesis,', 'proliferation,', 'survival,', and, metastasis, of, cancer, 'cells,']), verbo([leading]), complemento([to, the, cancer, progression])]). relacion([sujeto(['Thus,', nucleolin, may, be, a, novel, and, promising]), verbo([target]), complemento([for, 'anti-cancer', treatment])]). relacion([sujeto(['Here,', we, describe, how, nucleolin]), verbo([act]), complemento([functions, in, cancer, development, and, describe, 'nucleolin-dependent', 'anti-cancer', therapies])]). relacion([sujeto(['The', 'Subjects', of, this, study, were, persons, with, severe, mental, illness, diagnosed, with, 'schizophrenia,', major, 'depression,', or, bipolar, disorder, '(', 'ICD-10)', and, cognitive, dysfunction, who]), verbo([participated]), complemento([in, both, cognitive, remediation, using, the, 'Thinking', 'Skills', for, 'Work', program, and, supported, employment, program, in, a, 'multisite,', randomized, controlled, study])]). relacion([sujeto(['A', cognitive, remediation, program, transferring, learning, skills, into, the, real, world, is, useful, to]), verbo([increase]), complemento([the, quality, of, working, life, in, supported, employment, services, for, persons, with, severe, mental, illness, and, cognitive, dysfunction, who, want, to, work, competitively])]). relacion([sujeto(['The', advancement, of, knowledge, and, development, of, policy, in, the, field, of, medical, education]), verbo([require]), complemento([critical, academic, discourse, among, the, most, intelligent, medical, 'educators;', and, critical, academic, discourse, requires, coffee])]). relacion([sujeto(['The', abstract, submission, process, '(', summed, up, 'by:', '\'', 'Yay!', 'It', was, accepted, for, 'presentation\'', '[', 'Deep', 'breath]', '\'', 'Oh', 'no…it', was, accepted, for, 'presentation\'),', the, '\'', juggling, 'act\'', of, parent, 'attendees,', the]), verbo([acting]), complemento([prowess, of, abstract, presenters, and, the, unapologetic, approach, to, buffet, eating, are, all, 'by-products', of, the, collision, of, true, intellects, among, medical, education, scholars])]). relacion([sujeto(['We', hold, these, rituals, in, high, regard, and, argue, that, they, are]), verbo([required]), complemento([to, advance, the, field, of, medical, education])]). relacion([sujeto(['These', rituals]), verbo([bind]), complemento([the, walls, supporting, true, progressive, thought, and, innovative, 'research,', all, fuelled, by, the, glass, of, wine, purchased, with, that, one, coveted, drink, ticket])]). relacion([sujeto(['To', highlight, the, 'organisation-level', 'management\'s', role, in, building, leadership, capacity, in, advanced, nurse, practitioners, and, the, need, for, appropriate, supports, to]), verbo([increase]), complemento([their, becoming, leaders])]). relacion([sujeto(['In', times, of, economic, 'constraint,', organisations, need, to, focus, their, efforts, on]), verbo([targeted]), complemento([leadership, initiatives])]). relacion([sujeto(['Advanced', nurse, practitioners, are, ideally, positioned, to]), verbo([act]), complemento([as, leaders, both, within, and, beyond, the, health, care, organisation])]). relacion([sujeto(['Nurse', executives]), verbo([have]), complemento([a, vital, role, in, influencing, the, 'organisation\'s', strategic, plan, and, making, a, business, case, for, prioritising, leadership, capacity, building, within, advanced, nurse, practitioners])]). relacion([sujeto(['A', challenge, for, nurse, executives, faced, with, competing, service, and, leadership, development, 'demands,']), verbo([involves]), complemento([strategic, 'decision-making', regarding, whether, the, advanced, nurse, 'practitioner\'s', role, is, limited, to, service, delivery, or, its, potential, in, leading, health, care, reforms, is, realised])]). relacion([sujeto(['In', 1997, ',', it, was, proposed, that, preeclampsia, arises, due, to, the]), verbo([loss]), complemento([of, 'VEGF', 'activity,', possibly, due, to, elevation, in, 'anti-angiogenic', 'factor,', soluble, 'Flt-1', '(', 'sFlt-1)'])]). relacion([sujeto(['We', demonstrated, that, heme, 'oxygenase-1', '(', 'HO-1)/carbon', monoxide, '(', 'CO)', pathway]), verbo([prevents]), complemento([placental, stress, and, suppresses, 'sFlt-1', and, sEng, release])]). relacion([sujeto(['These', molecules]), verbo([act]), complemento([as, the, inhibitor, systems, in, pregnancy, and, when, they, 'fail,', preeclampsia, is, triggered])]). relacion([sujeto(['Hypotheses', that, fail, to, meet, the, 'Bradford', 'Hill', causation, criteria, include, abnormal, spiral, artery, remodelling, and, inflammation, and, should, be, considered]), verbo([associated]), complemento([or, consequential, to, the, disorder])]). relacion([sujeto(['Identifying', the, candidates, on, the, roadmap, to, this, pathway, is, essential, in, developing, diagnostics, and, therapeutics, to]), verbo([target]), complemento([the, pathogenesis, of, preeclampsia])]). relacion([sujeto(['Cellular', organization, and, response, to, internal, and, external, stimuli, are]), verbo([mediated]), complemento([by, an, intricate, web, of, protein, interactions])]). relacion([sujeto(['Some', of, these, interactions, are]), verbo([regulated]), complemento([by, covalent, posttranslational, modifications, such, as, phosphorylation, and, acetylation])]). relacion([sujeto(['These', modifications, can, change, the, chemical, nature, of, the, interaction, interfaces, and]), verbo([modulate]), complemento([the, binding, affinity, of, the, interacting, partners])]). relacion([sujeto(['Protein', phosphorylation, may]), verbo([modulate]), complemento([the, activity, of, enzymes, by, modifying, their, 'conformation,', or, regulate, the, formation, of, complexes, by, creating, docking, sites, to, recruit, downstream, effectors])]). relacion([sujeto(['Families', of]), verbo([modular]), complemento(['domains,', such, as, 'SH2,', 'PTB,', and, 14, -, 3, -, 3, ',', act, as, &, 'quot;readers"', of, the, modification, event])]). relacion([sujeto(['Specificity', between, closely, related, domains, of, the, same, family, is]), verbo([mediated]), complemento([by, the, chemical, properties, of, the, domain, binding, surface, 'that,', aside, from, offering, a, hydrophilic, pocket, for, the, phosphorylated, 'residue,', shows, preference, for, specific, sequences])]). relacion([sujeto(['Although', the, protein, structure, and, the, cell, context, are, also, important, to]), verbo([ensure]), complemento(['specificity,', the, amino, acid, sequence, flanking, the, phosphorylation, site, defines, the, accuracy, of, the, recognition, 'process,', and, it, is, therefore, essential, to, define, the, binding, specificity, of, phosphopeptide, binding, domains, in, order, to, understand, and, to, infer, the, interaction, web, mediated, by, phosphopeptides])]). relacion([sujeto(['Methods', commonly, used, to, discover, new, interactions, '(', such, as, yeast, two, hybrid, and, phage, 'display)', are, not, suited, to, study, interactions, with]), verbo([phosphorylated]), complemento([proteins])]). relacion([sujeto(['On', the, other, 'hand,', peptide, arrays, are, a, powerful, approach, to, precisely, identify, the]), verbo([binding]), complemento([preference, of, phosphopeptide, recognition, domains])]). relacion([sujeto(['Here', we, describe, a, detailed, protocol, to, assemble, arrays, of, hundreds, to, thousands, 'phospho-peptides', and, to, screen, them, with, any]), verbo([modular]), complemento([domain, of, interest])]). relacion([sujeto(['Previous', research, undertaken, in, skill, acquisition, was, used, to]), verbo([provide]), complemento([support, for, the, framework])]). relacion([sujeto(['Methods', for, the, measurement, and, analysis, of, each, principle, are]), verbo([provided]), complemento([and, future, directions, for, the, longitudinal, assessment, of, skill, acquisition, are, discussed])]). relacion([sujeto(['Glu']), verbo([released]), complemento([from, neurons, is, taken, up, by, astrocytes, and, activated, there, by, glutamine, synthetase, '(', 'GS)', to, form, glutamine, '(', 'Gln)', which, upon, entry, to, neurons, is, degraded, back, to, 'Glu', by, 'phosphate-activated', glutaminase, '(', 'PAG):', this, chain, of, reactions, has, been, defined, as, the, 'glutamine/glutamate/cycle', '(', 'GGC)'])]). relacion([sujeto(['In', the, initial, phase, of, 'epileptogenesis,']), verbo([increased]), complemento(['Glu', supply, is, a, consequence, of, activation, of, its, turnover, in, 'GGC', by, 'Glu', released, by, a, primary, chemical, or, physical, stimulus])]). relacion([sujeto(['In', chronic, 'TLE,', profound, astrogliosis, and, demise, of, neurons, which, culminate, in, hippocampal, 'sclerosis,', are]), verbo([associated]), complemento([with, changes, in, 'GGC', which, act, in, concert, towards, increasing, the, extracellular, 'Glu', concentration])]). relacion([sujeto(['Deficiency', of, 'GS', and, of, the, astrocytic, 'Glu', 'transporter,', 'GLT-1,', impede, 'Glu', 'inactivation,', whereas, 'Glu']), verbo([release]), complemento([from, neurons, appears, facilitated, by, activation, of, 'PAG', and, increased, activity, of, the, neuronal, 'Glu', transporter, 'EAAC1'])]). relacion([sujeto(['Conclusions', derived, from, measurements, of, 'activities/expression', patterns, of, the, 'GGC', enzymes, and, transporter, moieties]), verbo([find]), complemento([support, in, metabolic, studies, employing, '(', 13, ')', 'C', labeled, 'Glu', precursors])]). relacion([sujeto(['Glu', reuptake, by, astrocytes, is, additionally, impeded, by, unfavorable, ion, gradients, resulting, from, ion, and, water, 'dyshomeostasis,', and, extracellular, 'Glu', concentration, is, further]), verbo([increased]), complemento([by, reduction, of, extracellular, space, due, to, edema, and, altered, cytoarchitecture, of, the, hippocampus])]). relacion([sujeto(['Living', in, 'high-density', groups, of, animals]), verbo([has]), complemento([advantages, and, disadvantages, for, mating])]). relacion([sujeto(['The', advantage, of, facilitated, mate]), verbo([finding]), complemento([is, compromised, by, difficulties, in, protecting, a, suitable, partner, from, competitors])]). relacion([sujeto(['Thus,', males, regularly, are, faced, with]), verbo([increased]), complemento([competition, for, 'sperm,', and, females, with, harassment, by, males, at, high, population, densities])]). relacion([sujeto(['To', cope, with, these, 'problems,', mating, tactics, and, mate, choice, mechanisms]), verbo([have]), complemento([to, be, adjusted])]). relacion([sujeto(['Males', of, the, 'Central', 'American', 'locust,', 'Schistocerca', 'piceifrons,']), verbo([release]), complemento(['sex-specific', 'volatiles,', which, were, identified, as, phenethyl, alcohol, '(', 'synonym:', 'phenyl-ethyl-alcohol,', 2, -, 'phenyl-1-ethanol,', 2, -, 'phenylethanol,', 'PEA),', '(', 'Z)-3-nonen-1-ol', '(', 3, -, 'Nol),', and, '(', 'Z)-2-octen-1-ol', '(', 2, -, 'Ool)'])]). relacion([sujeto(['Furthermore,', the]), verbo([release]), complemento([of, both, volatiles, was, coupled, to, males, reaching, sexual, 'maturity,', indicating, a, function, in, reproductive, behavior])]). relacion([sujeto(['In', this, 'way,', the, 'male-specific', volatiles]), verbo([act]), complemento([as, mate, assessment, pheromones, utilized, in, a, context, of, cryptic, female, choice])]). relacion([sujeto(['Schistocerca', piceifrons, males]), verbo([release]), complemento([a, virtually, unique, personal, pheromone, 'signature,', a, prerequisite, for, mate, assessment, pheromones])]). relacion([sujeto(['Biphobia', presents, via, several, 'preconceptions,', including, that, bisexuality, is, 'transitory,', and, that, bisexual, men]), verbo([act]), complemento([as, viral, bridges, between, men, who, have, sex, with, men, and, heterosexual, populations])]). relacion([sujeto(['Men']), verbo([reporting]), complemento([both, male, and, female, sexual, partners, '(', 'MSMW)', between, 2002, and, 2009, '(', 'n = 111)', were, classified, as, behaviorally, bisexual])]). relacion([sujeto(['No', evidence, was]), verbo([found]), complemento([supporting, the, transitory, nature, of, bisexuality])]). relacion([sujeto(['We']), verbo([found]), complemento([little, evidence, to, support, substantial, viral, bridging, behavior])]). relacion([sujeto(['Notably,', 'HIV-positive', 'MSMW']), verbo([reported]), complemento([lower, proportions, of, female, partners, than, 'HIV-negative', 'MSMW'])]). relacion([sujeto(['Our', results]), verbo([provide]), complemento([no, empirical, support, for, bisexual, transience, and, scant, support, for, viral, bridging, hypotheses])]). relacion([sujeto(['Our', results]), verbo([provide]), complemento([key, data, showing, that, male, bisexual, behavior, may, be, stable, over, long, time, periods, and, that, behaviorally, bisexual, 'men\'s', risk, to, female, sexual, partners, may, be, lower, than, expected])]). relacion([sujeto(['Marine', microorganisms, such, as, phytoplanktons, are, a, rich, resource, of, bioactive, components, with, antioxidant, and, 'anti-proliferative', activities, that, can]), verbo([act]), complemento([as, novel, functional, food, ingredients])]). relacion([sujeto([pevalekii, were]), verbo([found]), complemento([to, be, strongly, correlated, with, their, antioxidant, activities, evaluated, by, the, 'DPPH,', 'TEAC', and, 'FRAP', assays])]). relacion([sujeto(['Therefore,', individual, carotenoid, pigments, seemed, to, be, mainly, responsible, for, the, antioxidant, and, 'anti-proliferative', '(', or, 'anticancer)', activities]), verbo([found]), complemento([in, the, solvent, extracts, of, the, five, phytoplanktons])]). relacion([sujeto(['Hence', these, phytoplanktons]), verbo([have]), complemento([the, potential, as, novel, sources, of, natural, food, antioxidants, and, anticancer, agents, to, be, used, as, active, ingredients, in, functional, food, products])]). relacion([sujeto(['North-east', region, of, 'India']), verbo([has]), complemento([consistent, role, in, the, spread, of, multi, drug, resistant, 'Plasmodium', '(', 'P'])]). relacion([sujeto(['This', study]), verbo([suggests]), complemento([that, sulfadoxine, resistant, isolates, are, still, migrating, from, its, epicenter, to, the, other, parts, of, 'Southeast', 'Asia', and, hence, control, and, elimination, of, the, drug, resistant, isolates, have, become, impedimental])]). relacion([sujeto([falciparum, populations, in, different, areas, may, undergo, selection, of, particular, sulfadoxine, resistant, haplotypes, either, in, the, presence, of, drug, or, after, its, removal, to]), verbo([maintain]), complemento([their, plasticity])]). relacion([sujeto(['Exosomes,', as, a, mediator, of, 'cell-to-cell', transfer, of, genetic, 'information,']), verbo([act]), complemento([an, important, role, in, intercommunication, between, tumor, cells, and, their, niche, including, 'fibroblasts,', endothelial, 'cells,', adipocytes, and, monocytes])]). relacion([sujeto(['Several', studies]), verbo([have]), complemento([shown, that, tumor, cells, can, influence, their, neighboring, cells, by, releasing, exosomes])]). relacion([sujeto(['These', exosomes]), verbo([provide]), complemento([signaling, cues, for, 'stimulation,', 'activation,', proliferation, and, differentiation, of, cells])]). relacion([sujeto(['Exosomes', contain, 'mRNAs,', microRNAs, '(', 'miRNA),', and, proteins, that, could, be, transferred, to]), verbo([target]), complemento([cells, inducing, genetic, and, epigenetic, changes])]). relacion([sujeto(['By', facilitating, the, horizontal, transfer, of, bioactive, molecules, such, as, 'proteins,', 'RNAs', and, 'microRNAs,', they, are, now, thought, to]), verbo([have]), complemento([vital, roles, in, tumor, invasion, and, 'metastases,', 'inflammation,', 'coagulation,', and, stem, cell, renewal, and, expansion])]). relacion([sujeto(['Extracellular', microRNAs, are]), verbo([released]), complemento([from, cells, both, passively, and, actively])]). relacion([sujeto(['The', presence, of, these, microRNAs, in, the, tumour, microenvironment, '(', 'TME)', can, significantly, impact, on, the, plasticity, of, cancer, cells]), verbo([leading]), complemento([to, the, promotion, of, metastatic, and, angiogenic, processes])]). relacion([sujeto(['These', extracellular, microRNAs, can]), verbo([act]), complemento([not, only, on, other, cancer, 'cells,', but, also, cells, present, in, the, 'TME,', such, as, immune, 'cells,', endothelial, 'cells,', 'fibroblasts,', and, others, acting, to, subvert, the, host, immune, system, and, drive, tumour, progression])]). relacion([sujeto(['In', this, review, we, highlight, the, current, understanding, of, both, the, mechanisms, by, which, microRNAs, are]), verbo([released]), complemento([from, tumour, cells, and, the, downstream, functional, effects, that, extracellular, microRNAs, have, on, recipient, cells])]). relacion([sujeto(['As', an, important, component, of, ascending]), verbo([activating]), complemento(['systems,', brainstem, cholinergic, neurons, in, the, pedunculopontine, tegmental, nucleus, '(', 'PPTg)', are, involved, in, the, regulation, of, motor, control, '(', 'locomotion,', posture, and, 'gaze)', and, cognitive, processes, '(', 'attention,', learning, and, 'memory)'])]). relacion([sujeto(['The', 'PPTg', is, highly, interconnected, with, several, regions, of, the, basal, 'ganglia,', and, one, of, its, key, functions, is, to]), verbo([regulate]), complemento([and, relay, activity, from, the, basal, ganglia])]). relacion([sujeto(['Together,', they]), verbo([have]), complemento([been, implicated, in, the, motor, control, system, '(', such, as, voluntary, movement, initiation, or, 'inhibition),', and, modulate, aspects, of, executive, function, '(', such, as, 'motivation)'])]). relacion([sujeto(['In', addition, to, its, intimate, connection, with, the, basal, 'ganglia,', projections, from, the, 'PPTg', to, the, cerebellum]), verbo([have]), complemento([been, recently, reported, to, synaptically, activate, the, deep, cerebellar, nuclei])]). relacion([sujeto(['Here,', we]), verbo([suggest]), complemento([that, the, 'PPTg', may, also, act, as, an, interface, device, between, the, basal, ganglia, and, cerebellum])]). relacion([sujeto(['As', 'such,', part, of, the, therapeutic, effect, of, 'PPTg', deep, brain, stimulation, '(', 'DBS)', to, relieve, gait, freezing, and, postural, instability, in, advanced, 'Parkinson\'s', disease, '(', 'PD)', patients, might, also]), verbo([involve]), complemento([modulation, of, the, cerebellum])]). relacion([sujeto(['It']), verbo([has]), complemento([been, confirmed, that, inflammatory, cytokines, are, involved, in, the, progression, of, pterygium])]). relacion([sujeto(['Histamine', can]), verbo([enhance]), complemento([proliferation, and, migration, of, many, cells])]). relacion([sujeto(['Histamine', may, play, an, important, role, in, the, proliferation, of, 'HPFs', and]), verbo([act]), complemento([through, 'H1R'])]). relacion([sujeto(['In', 'Australia,', as, in, other, 'countries,', the, initial, focus]), verbo([has]), complemento([been, on, the, harmonisation, of, the, more, commonly, measured, analytes])]). relacion([sujeto(['Calculated', parameters, that, are]), verbo([reported]), complemento([by, laboratories, and, used, for, clinical, 'decision-making', should, undergo, the, same, robust, process, of, harmonisation, as, is, the, case, for, the, measured, analytes])]). relacion([sujeto(['To', investigate, pathways, towards, the, harmonisation, of, calculated, 'parameters,', three, commonly]), verbo([reported]), complemento([parameters, are, considered])]). relacion([sujeto(['Calculated', 'osmolality,', the, anion, gap, and, 'albumin-adjusted', calcium, are, all, derived, from, common, analytes, which]), verbo([have]), complemento([individually, been, considered, for, harmonisation])]). relacion([sujeto(['They', present, different, 'methodological,', measurement, uncertainty, and, terminological, hurdles, to, harmonisation, and, are, likely, to]), verbo([require]), complemento([different, pathways, and, solutions])]). relacion([sujeto(['This', need, is, based, on, good, laboratory, 'practice,']), verbo([providing]), complemento([the, clinician, with, results, that, allow, appropriate, and, reliable, clinical, interpretation, and, progression, further, toward, the, national, 'e-health', framework, and, a, single, electronic, health, record])]). relacion([sujeto(['In', 2015, ',', after, further, stakeholder, 'consultation,', a, second, group, of, six, harmonised, 'RIs', for, common, chemistry, analytes]), verbo([has]), complemento([been, proposed, for, adults, which, includes, 'ALT', and, 'AST', where, methods, do, not, use, 'pyridoxal-5\'-phosphate', as, an, activator, and, lipase, excluding, the, 'Ortho', 'Clinical', 'Diagnostics', and, 'Siemens', 'Dimension', assays])]). relacion([sujeto(['For', more, than, a, decade, there]), verbo([has]), complemento([been, a, global, effort, to, harmonise, all, phases, of, the, testing, 'process,', with, particular, emphasis, on, the, most, frequently, utilised, measurands])]). relacion([sujeto(['In', 'addition,', it, is, recognised, that, calculated, parameters, derived, from, these, measurands, should, also, be, a]), verbo([target]), complemento([for, harmonisation])]). relacion([sujeto(['Using', data, from, the, 'Aussie', 'Normals', study, we]), verbo([report]), complemento([reference, intervals, for, three, calculated, 'parameters:', serum, 'osmolality,', serum, anion, gap, and, 'albumin-adjusted', serum, calcium])]). relacion([sujeto(['An']), verbo([enhanced]), complemento([intensity, of, the, localized, surface, plasmon, resonances, '(', 'LSPRs)', supported, by, the, hybrid, nanostructures, can, be, 'obtained,', which, induces, a, much, enhanced, fluorescent, intensity, from, the, dye, coated, hybrid, nanostructures])]). relacion([sujeto(['Moreover,', the, graphene, sheets, covering, completely, and, uniformly, on, the, 'Cu', 'NPs']), verbo([act]), complemento([as, a, passivation, layer, to, protect, the, underlying, metal, surface, from, air, oxidation])]). relacion([sujeto(['As', a, 'result,', the, stability, of, the, 'LSPRs', for, the, hybrid, nanostructures, is, much]), verbo([enhanced]), complemento([compared, to, that, of, the, bare, 'Cu', 'NPs'])]). relacion([sujeto(['The', 'transfer-free', hybrid, nanostructures, with]), verbo([enhanced]), complemento([intensity, and, stability, of, the, 'LSPRs', will, enable, their, much, broader, applications, in, photonics, and, optoelectronics])]). relacion([sujeto(['Dexmedetomidine', '(', 'DEX)', may]), verbo([act]), complemento([as, an, antioxidant, through, regulation, of, 'TRPM2', and, 'TRPV1', channel, activations, in, the, neurons, by, reducing, cerebral, 'ischemia-induced', oxidative, stress, and, apoptosis])]). relacion([sujeto(['The', 'DEX', and, 'ISC+DEX', treatments, also]), verbo([decreased]), complemento([the, expression, levels, of, caspase, 3, ',', caspase, 9, ',', and, poly, '(', 'ADP-ribose)', polymerase, in, the, hippocampus, and, 'DRG'])]). relacion([sujeto(['Therefore,', 'DEX', can]), verbo([have]), complemento([remarkable, neuroprotective, impairment, effects, in, the, hippocampus, and, 'DRG', of, 'ISC-induced', rats])]). relacion([sujeto(['More', than, 40, antimicrobial, peptides, and, proteins, '(', 'AMPs)', are]), verbo([expressed]), complemento([in, the, oral, cavity])]). relacion([sujeto(['These', 'AMPs']), verbo([have]), complemento([been, organized, into, 6, functional, 'groups,', 1, of, 'which,', cationic, 'AMPs,', has, received, extensive, attention, in, recent, years, for, their, promise, as, potential, antibiotics])]). relacion([sujeto(['Cationic', 'AMPs', typically, exhibit, an, amphipathic, 'conformation,', which, allows]), verbo([increased]), complemento([interaction, with, negatively, charged, bacterial, membranes])]). relacion([sujeto(['As', a, 'consequence,', a, single, peptide, can]), verbo([act]), complemento([through, several, mechanisms, depending, on, the, 'peptide\'s', 'structure,', the, 'peptide:lipid', 'ratio,', and, the, properties, of, the, lipid, membrane])]). relacion([sujeto(['Accumulating', evidence, shows, that, in, addition, to]), verbo([acting]), complemento([at, the, cell, 'membrane,', 'AMPs', may, act, on, the, cell, 'wall,', inhibit, protein, folding, or, enzyme, 'activity,', or, act, intracellularly])]). relacion([sujeto(['Therefore,', once, a, peptide]), verbo([has]), complemento([reached, the, cell, 'wall,', cell, 'membrane,', or, its, internal, 'target,', the, difference, in, mechanism, of, action, on, 'gram-negative', and, 'gram-positive', bacteria, may, be, less, pronounced, than, formerly, assumed])]). relacion([sujeto(['While', 'AMPs', should, not]), verbo([cause]), complemento([widespread, resistance, due, to, their, preferential, attack, on, the, cell, 'membrane,', in, cases, where, specific, protein, targets, are, 'involved,', the, possibility, exists, for, genetic, mutations, and, bacterial, resistance])]). relacion([sujeto(['Indeed,', the, potential, clinical, use, of, 'AMPs']), verbo([has]), complemento([raised, the, concern, that, resistance, to, therapeutic, 'AMPs', could, be, associated, with, resistance, to, endogenous, 'host-defense', peptides])]). relacion([sujeto(['Current', evidence]), verbo([suggests]), complemento([that, this, is, a, rare, event, that, can, be, overcome, by, subtle, structural, modifications, of, an, 'AMP'])]). relacion([sujeto(['Rab', guanosine, triphosphatases, '(', 'GTPases)', control, cellular, trafficking, pathways, by]), verbo([regulating]), complemento([vesicle, 'formation,', 'transport,', and, tethering])]). relacion([sujeto(['Rab11', and, its, paralogs]), verbo([regulate]), complemento([multiple, secretory, and, endocytic, recycling, 'pathways,', yet, the, guanine, nucleotide, exchange, factor, '(', 'GEF)', that, activates, 'Rab11', in, most, eukaryotic, cells, is, unresolved])]). relacion([sujeto(['The', large, multisubunit, transport, protein, particle, '(', 'TRAPP)', 'II', complex]), verbo([has]), complemento([been, proposed, to, act, as, a, 'GEF', for, 'Rab11', based, on, genetic, 'evidence,', but, conflicting, biochemical, experiments, have, created, uncertainty, regarding, 'Rab11', activation])]). relacion([sujeto(['Using', physiological, 'Rab-GEF', reconstitution, 'reactions,', we, now]), verbo([provide]), complemento([definitive, evidence, that, 'TRAPPII', is, a, bona, fide, 'GEF', for, the, yeast, 'Rab11', homologues, 'Ypt31/32'])]). relacion([sujeto(['We', also, uncover, a, direct, role, for, 'Arf1,', a, distinct, 'GTPase,', in]), verbo([recruiting]), complemento(['TRAPPII', to, anionic, membranes])]). relacion([sujeto(['Given', the, known, role, of, 'Ypt31/32', in]), verbo([stimulating]), complemento([activation, of, 'Arf1,', a, bidirectional, cross, talk, mechanism, appears, to, drive, biogenesis, of, secretory, and, endocytic, recycling, vesicles])]). relacion([sujeto(['By', coordinating, simultaneous, activation, of, two, essential, 'GTPase', 'pathways,', this, mechanism]), verbo([ensures]), complemento([recruitment, of, the, complete, set, of, effectors, needed, for, vesicle, 'formation,', 'transport,', and, tethering])]). relacion([sujeto(['NTW,', a, secondary, care, 'NHS', 'Foundation', 'Trust']), verbo([providing]), complemento([mental, health, and, disability, services, in, the, 'north-east', of, 'England,', in, conjunction, with, 'Northumbria', 'Police', 'Service'])]). relacion([sujeto(['There', were, 1623, 'ST', contacts, in, the, first, 3, localities, to]), verbo([have]), complemento([a, 'ST', service, during, its, first, 'year;', there, were, also, 403, fewer, 'S136', detentions])]). relacion([sujeto(['There', is, evidence, to, support, the, hypothesis, that, 'ST']), verbo([decreases]), complemento([the, rate, of, s136, detention])]). relacion([sujeto(['To', further, understand, the]), verbo([associated]), complemento([diagnostic, 'processes,', it, is, also, important, to, explore, the, patient, perspectives, expressed, in, the, 'free-text', comments])]). relacion([sujeto(['To', use, the, 'free-text', data]), verbo([provided]), complemento([by, patients, completing, the, 'ICBP4', survey, to, augment, the, understanding, of, 'patients\'', perspectives, of, their, diagnostic, journey])]). relacion([sujeto(['Newly-diagnosed', patients, with, either, 'breast,', 'ovarian,', 'colorectal,', or, lung, cancer, were, identified, from, registry, data, and, then, invited, by, their, 'GPs', to]), verbo([participate]), complemento([in, the, survey])]). relacion([sujeto(['A', thematic, framework, was, used, to, analyse, the, 'free-text', comments]), verbo([provided]), complemento([at, the, end, of, the, 'ICBP4', survey])]). relacion([sujeto(['The', 'free-text', data]), verbo([provided]), complemento([information, about, 'patients\'', perspectives, of, the, diagnostic, journey])]). relacion([sujeto(['Analysis', identified, factors, that]), verbo([acted]), complemento([as, either, barriers, or, facilitators, at, different, stages, of, the, diagnostic, process])]). relacion([sujeto(['Some', 'factors,', such, as, 'screening,', 'doctor-patient', 'familiarity,', and, private, 'treatment,']), verbo([acted]), complemento([as, both, barriers, and, facilitators, depending, on, the, context])]). relacion([sujeto(['It', is, important, that, clinicians, are, aware, of, how, these, factors, may]), verbo([interact]), complemento([with, individual, clinical, cases, and, either, 'facilitate,', or, act, as, a, barrier, 'to,', subsequent, cancer, diagnosis])]). relacion([sujeto(['A', major, limitation, in, effectively, treating, 'PDAC', using, conventional, and]), verbo([targeted]), complemento([chemotherapeutic, 'agents,', is, inadequate, drug, delivery, to, the, target, 'location,', predominantly, due, to, a, poorly, 'vascularised,', desmoplastic, tumour, microenvironment])]). relacion([sujeto(['The', high, vascular, percentage, correlated, to, the, transient]), verbo([decrease]), complemento([and, overall, inhibition, of, the, tumour, volumes])]). relacion([sujeto(['Nonsynaptic', epileptiform, activities, '(', 'NEA)', were]), verbo([induced]), complemento([by, means, of, the, 'zero-Ca(2+)', and, 'high-K(+)', model, using, hippocampal, slices, and, were, recorded, in, the, 'DG'])]). relacion([sujeto(['An']), verbo([increase]), complemento([in, the, 'DC', shifts, associated, with, epileptiform, discharges, was, present, with, the, low, dose])]). relacion([sujeto(['This']), verbo([increase]), complemento([was, correlated, with, the, increment, of, 'NKCC1', expression])]). relacion([sujeto(['Confocal', microscopy, images, indicate, the, 'NKCC1']), verbo([increase]), complemento([was, pronounced, in, the, initial, axonal, segment, of, granule, cells])]). relacion([sujeto(['The', blockage, of, these, cotransporters, during, 'NEA', induction, with, bumetanide]), verbo([suppressed]), complemento([the, 'DC', shift, increase, and, diminished, all, parameters, of, 'NEA', that, were, quantified, for, all, groups, treated, with, ethanol])]). relacion([sujeto(['Therefore,', the]), verbo([increase]), complemento([in, 'NKCC1', expression, and, the, effective, activity, of, this, 'cotransporter,', which, were, observed, in, the, treated, 'groups,', suggest, that, drugs, that, act, for, block, 'NKCC1', represent, promising, strategies, for, diminishing, the, effects, of, alcohol, damage, on, the, brain])]). relacion([sujeto(['The', generation, of, 'DNA', modifications, in, cells, is, in, most, cases, accidental, and]), verbo([associated]), complemento([with, detrimental, consequences, such, as, increased, mutation, rates, and, an, elevated, risk, of, malignant, transformation])]). relacion([sujeto(['Accordingly,', repair, enzymes]), verbo([involved]), complemento([in, the, removal, of, the, modifications, have, primarily, a, protective, function])]). relacion([sujeto(['More', 'recently,', considerable, evidence]), verbo([has]), complemento([been, obtained, that, also, 8, -, 'oxo-7,8-dihydroguanine', '(', 8, -, 'oxoG),', a, frequent, 'pro-mutagenic', 'DNA', modification, generated, by, endogenous, or, exogenous, reactive, oxygen, species, '(', 'ROS),', has, distinct, roles, in, the, regulation, of, both, transcription, and, signal, transduction])]). relacion([sujeto(['In', 'addition,', a, complex, of, 'OGG1', with, the, excised, free, substrate, base, was, demonstrated, to]), verbo([act]), complemento([as, a, guanine, nucleotide, exchange, factor, '(', 'GEF)', for, small, 'GTPases', such, as, 'Ras,', 'Rac', and, 'Rho,', thus, stimulating, signal, transduction])]). relacion([sujeto(['The', various, findings, and, intriguing, novel, mechanisms]), verbo([suggested]), complemento([will, be, described, and, compared, in, this, review])]). relacion([sujeto(['Seeking', out, actionable, aberrations, that, can, be, selectively]), verbo([targeted]), complemento([by, drug, compounds, promises, to, optimize, treatment, efficacy, and, minimize, toxicity])]). relacion([sujeto(['Utilizing', these, different]), verbo([targeted]), complemento([agents, in, combination, or, in, sequence, may, further, delay, resistance, to, treatments, and, prolong, antitumor, responses])]). relacion([sujeto(['Corresponding', advances, in, companion, biomarker, 'development,', novel, methods, of, serial, tumor, 'assessments,', and, innovative, trial, designs]), verbo([act]), complemento([synergistically, to, further, precision, medicine])]). relacion([sujeto(['A', newly, isolated, 'endo-β-1,4-xylanase', '(', 'Xyn10E)', from, 'Paenibacillus', curdlanolyticus, 'B-6']), verbo([has]), complemento([a, modular, structure, consisting, of, a, family, 22, 'carbohydrate-binding', module, '(', 'CBM),', a, glycoside, hydrolase, '(', 'GH)', family, 10, catalytic, 'domain,', two, fibronectin, type, 'III', '(', 'Fn3)', 'domains,', and, a, family, 3, 'CBM', at, the, 'C-terminus'])]). relacion([sujeto(['Intact', 'Xyn10E', '(', 'rXyn10E),', 'CBM22-deleted', 'Xyn10E', '(', 'X-CBM3),', 'CBM3-deleted', 'Xyn10E', '(', 'X-CBM22),', and, 'GH10', catalytic, domain, only, '(', 'X-GH10)', were]), verbo([expressed]), complemento([in, 'Escherichia', coli])]). relacion([sujeto(['Although', 'X-CBM3', and, 'X-GH10', had, drastically, reduced, xylanase, and, 'β-glucanase', 'activities,', 'X-CBM22', mostly]), verbo([retained]), complemento([these, activities])]). relacion([sujeto(['Similar', 'Km', values, were, obtained, for, rXyn10E, and, 'X-CBM3,', but, kcat, and, 'kcat/Km', values, for, 'X-CBM3', and, 'X-GH10', were, lower, than, those, for, 'rXyn10E,']), verbo([suggesting]), complemento([that, 'CBM22', of, 'Xyn10E', may, contribute, to, catalytic, efficiency])]). relacion([sujeto(['In']), verbo([binding]), complemento(['assays,', 'X-CBM3', was, still, able, to, bind, to, 'β-glucan,', soluble, 'xylan,', insoluble, 'xylan,', and, cellulose, through, 'GH10', and, 'CBM3'])]). relacion([sujeto(['These', results, indicate, that, 'CBM22']), verbo([has]), complemento([an, important, role, not, only, in, binding, to, xylan, and, 'β-glucan', but, also, in, feeding, both, polysaccharides, into, the, neighboring, 'GH10', catalytic, domain])]). relacion([sujeto(['These', results, indicate, that, 'Xyn10E', and, 'Xyn11A']), verbo([act]), complemento([synergistically, on, lignocellulosic, 'biomass,', and, 'CBM22', is, essential, for, efficient, degradation, of, lignocellulosic, materials])]). relacion([sujeto(['While', many, reasons]), verbo([have]), complemento([been, advanced, to, explain, the, persistently, poor, 'outcomes,', management, of, the, system, has, been, found, to, play, a, key, role])]). relacion([sujeto(['In', this, 'study,', we, examined, how, district, managers, in, a, rural, setting, in, 'Uganda', perceived, existing, approaches, to, strengthening, management, so, as, to]), verbo([provide]), complemento([a, pragmatic, and, synergistic, model, for, improving, management, capacity, building])]). relacion([sujeto(['A', competent, manager, was, understood, as, one, who, knew, 'his/her', 'roles,', was, well, informed, and, was, empowered, to]), verbo([execute]), complemento([management, functions])]). relacion([sujeto(['Professionalizing', health, managers, which, was, viewed, as, the, 'foundation,', the, use, of, engaging, learning, approaches, as, the, inside, contents, and, having, a, supportive, work, environment, the, frame, of, the, model, were, the, 'sub-processes']), verbo([involved]), complemento([in, the, model])]). relacion([sujeto(['The', model, developed, in, our, study, makes, four, central, contributions, to]), verbo([enhance]), complemento([the, 'WHO', framework, and, the, existing, literature])]). relacion([sujeto(['Second,', our, model]), verbo([suggests]), complemento([the, need, for, professionalization, of, health, managers, at, different, levels, of, the, health, system])]). relacion([sujeto(['Third,', our, model, underscores, the, benefits, that, could, be, accrued, from, the, use, of, engaging, learning, approaches, through, prolonged, and, sustained, processes, that]), verbo([act]), complemento([in, synergy])]). relacion([sujeto(['Lastly,', our, model, postulates, that, different, resource, investments, and, a, varied, range, of, stakeholders, could, be]), verbo([required]), complemento([at, each, of, the, 'sub-processes'])]). relacion([sujeto(['Triple-negative', breast, cancer, '(', 'TNBC)']), verbo([has]), complemento([a, high, risk, of, relapse, and, there, are, few, chemotherapy, options])]). relacion([sujeto(['Although', 5, -, hydroxytryptamine, '(', 5, -, 'HT,', 'serotonin)', signaling, pathways]), verbo([have]), complemento([been, suggested, as, potential, targets, for, 'anti-cancer', drug, 'development,', the, mechanism, responsible, for, the, action, of, 5, -, 'HT', in, 'TNBC', remains, unknown])]). relacion([sujeto(['TNBC', cell, lines, '(', 'MDA-MB-231,', 'HCC-1395,', and, 'Hs578T)']), verbo([expressed]), complemento([higher, levels, of, tryptophan, hydroxylase, 1, '(', 'TPH1)', than, 'hormone-responsive', breast, cancer, cell, lines, '(', 'MCF-7', and, 'T47D)'])]). relacion([sujeto(['In', 'MDA-MB-231', 'cells,', 5, -, 'HT']), verbo([promoted]), complemento([invasion, and, proliferation, via, 5, -, 'HT7', 'receptor,', and, 'interestingly,', the, stimulatory, effect, of, 5, -, 'HT', on, 'MDA-MB-231', cell, invasion, was, stronger, than, its, effect, on, proliferation])]). relacion([sujeto(['Also,', 5, -, 'HT']), verbo([increased]), complemento([the, protein, expressions, of, 'TPH1', and, 'VEGF', in, 'MDA-MB-231', cells])]). relacion([sujeto(['These', results]), verbo([provide]), complemento([insight, of, the, stimulatory, effect, of, 5, -, 'HT', on, breast, cancer, 'progression;', 5, -, 'HT', was, found, to, act, more, strongly, during, the, first, stage, of, metastasis, '(', during, invasion, and, 'migration)', than, during, the, later, proliferative, phase, after, local, invasion])]). relacion([sujeto(['Interestingly,', these, actions, of, 5, -, 'HT', were]), verbo([inhibited]), complemento([by, 'BJ-1113,', a, 6, -, 'amino-2,4,5-trimethylpyridin-3-ol', analog])]). relacion([sujeto([5, -, 'HT7', receptor, which]), verbo([mediates]), complemento([5, -, 'HT-induced', cancer, progression, is, a, potential, therapeutic, target, in, 'TNBC,', and, 'BJ-1113', offers, a, novel, scaffold, for, the, development, of, 'anti-cancer', agents, against, 'TNBC'])]). relacion([sujeto(['Premature', differentiation, of, 'cells,', disruption, of, cell, cycle, 'timing,', excessive, 'apoptosis,', 'and/or', incorrect, neuronal, migration, signals, can]), verbo([have]), complemento([devastating, 'effects,', resulting, in, a, number, of, neurodevelopmental, disorders, involving, microcephaly, 'and/or', lissencephaly])]). relacion([sujeto(['Though', genes, encoding, many, key, players, in, cortical, development]), verbo([have]), complemento([been, 'identified,', our, understanding, remains, incomplete])]). relacion([sujeto(['We', show, that, the, gene, encoding, 'Akirin2,', a, small]), verbo([nuclear]), complemento(['protein,', is, expressed, in, the, embryonic, telencephalon])]). relacion([sujeto(['Converging', evidence, indicates, that, 'Akirin2']), verbo([acts]), complemento([as, a, bridge, between, transcription, factors, '(', including, 'Twist', and, 'NF-κB', 'proteins)', and, the, 'BAF', '(', 'SWI/SNF)', chromatin, remodeling, machinery, to, regulate, patterns, of, gene, expression])]). relacion([sujeto(['Constitutive', knockout, of, 'Akirin2', is, early, embryonic, lethal, in, 'mice,', while, restricted]), verbo([loss]), complemento([in, 'B', cells, led, to, disrupted, proliferation, and, cell, survival])]). relacion([sujeto(['In', situ, hybridization, for, 'Wnt3a', and, 'Wnt-responsive', genes]), verbo([suggest]), complemento([defective, formation, 'and/or', function, of, the, cortical, hem, in, 'Akirin2', null, mice])]). relacion([sujeto(['Furthermore,', the, apical, ventricular, surface, becomes, 'disrupted,', and, 'Sox2-positive', progenitors, are]), verbo([found]), complemento([to, &, 'quot;spill"', into, the, lateral, ventricle])]). relacion([sujeto(['Our', data, demonstrate, a, 'previously-unsuspected', role, for, 'Akirin2', in, early, cortical, development, 'and,', given, its, known]), verbo([nuclear]), complemento(['roles,', suggest, that, it, may, act, to, regulate, gene, expression, patterns, critical, for, early, progenitor, cell, behavior, and, cortical, neuron, production])]). relacion([sujeto(['Baseline', data, '(', 2006, -, 2009, ')', from, the, 45, and, 'Up', 'Study,', an, 'Australian', cohort]), verbo([involving]), complemento([267, ',', 153, men, and, women, aged, '≥', 45, ',', were, linked, to, hospital, and, death, data, '(', to, 'December', 2013, ')'])]). relacion([sujeto(['For', both, primary, and, secondary, 'events,', incidence]), verbo([increased]), complemento([with, decreasing, 'education,', with, the, absolute, difference, between, education, groups, largest, for, secondary, events])]). relacion([sujeto(['The']), verbo([act]), complemento([of, detecting, bodily, changes, is, a, 'pre-requisite', for, subsequent, responses, to, 'symptoms,', such, as, seeking, medical, help])]). relacion([sujeto(['Results', from, logistic, regression, analysis, revealed, that, paying, more, attention, to, bodily, changes, was, significantly]), verbo([associated]), complemento([with, 'help-seeking', for, cancer, symptoms, '(', 'OR', =, 1.44, ;, 1.06, -, 1.97, ')', ',', after, controlling, for, 'socio-demographics,', current, illness, and, cancer, worry])]). relacion([sujeto(['Being', more, sensitive, to, bodily, changes, was, not, significantly]), verbo([associated]), complemento([with, 'help-seeking'])]). relacion([sujeto(['More', needs, to, be, understood, about, the, impact, this, might]), verbo([have]), complemento([on, 'cancer-related', anxiety])]). relacion([sujeto(['From', 1979, to, 2014, ',', noise, exposure]), verbo([has]), complemento([decreased])]). relacion([sujeto(['Overall', noise, levels, in, mines]), verbo([have]), complemento([been, decreasing])]). relacion([sujeto(['However,', this]), verbo([decrease]), complemento([has, not, been, uniform, across, all, mining, sectors])]). relacion([sujeto(['The', exposure, predictions, from, the, model, will, be, useful, to, help, predict, hearing]), verbo([loss]), complemento([in, workers, in, the, mining, industry])]). relacion([sujeto(['After', establishing, a, set, of, design, and, performance, 'objectives,', a, package, of, design, solutions, was, developed, for, 1000, -, year, surface, barriers, over]), verbo([nuclear]), complemento([waste, sites])]). relacion([sujeto(['The', barrier, was, tested, to, evaluate, 'surface-barrier', design, and, performance, at, the, field, scale, under, conditions, of]), verbo([enhanced]), complemento([and, natural, precipitation, and, of, no, vegetation])]). relacion([sujeto(['Given', the, 'two-decade', record, of, successful, performance, and, consideration, of, the, processes, and, mechanisms, that, could, affect, barrier, stability, and, hydrology, in, the, 'future,', the, results]), verbo([suggest]), complemento([the, 'PHB', is, very, likely, to, perform, for, its, 1000, -, year, design, life])]). relacion([sujeto(['This', conclusion, is, based, on, two, 'assumptions:', '(', 1, ')', the, exposed, subgrade, receives, protection, against, erosion, and, '(', 2, ')', institutional, controls]), verbo([prevent]), complemento([inadvertent, human, activity, at, the, barrier])]). relacion([sujeto(['The', 'PHB', design, can, serve, as, the, basis, for, 'site-specific', barriers, over, waste, sites, containing, underground]), verbo([nuclear]), complemento(['waste,', uranium, mine, 'tailings,', and, hazardous, mine, waste])]). relacion([sujeto(['Adult', participants, '(', 78, '%', 'female,', 25, '%', with, high, school, or, less, 'education,', 30, '%', 'unemployed)', were]), verbo([recruited]), complemento([into, the, 'single-arm', pilot, trial, '(', 'N=99)', of, 'SmartQuit', 2.0, with, a, 'two-month', 'follow-up', '(', 85, '%', 'retention)'])]). relacion([sujeto([0, ')', ',', 81, '%']), verbo([found]), complemento([the, 'ACT', exercises, useful, for, quitting, '(', vs])]). relacion([sujeto(['FLT3-ITD']), verbo([expressing]), complemento([cells, have, been, shown, to, generate, increased, levels, of, reactive, oxygen, species, '(', 'ROS),', in, particular, 'NADPH', oxidase, '(', 'NOX)-generated', 'ROS', which, act, as, 'pro-survival', signals])]). relacion([sujeto(['The', purpose, of, this, study, is, to, investigate, 'FLT3-ITD', production, of, 'ROS', at, the, plasma, membrane, and, 'ER', in, the, 'FLT3-ITD']), verbo([expressing]), complemento(['AML', cell, line, 'MV4-11'])]). relacion([sujeto(['Receptor', trafficking, 'inhibitors;', 'Tunicamycin', and, 'Brefeldin', 'A']), verbo([induce]), complemento(['ER', retention, of, 'FLT3-ITD,', resulting, in, a, decrease, in, protein, expression, of, 'NOX4', and, its, partner, protein, 'p22(phox),', thus, demonstrating, the, critical, importance, of, 'FLT3-ITD', localization, for, the, generation, of, 'pro-survival', 'ROS'])]). relacion([sujeto(['We']), verbo([found]), complemento([that, 'PI3K/AKT', signaling, only, occurs, when, 'FLT3-ITD', is, expressed, at, the, plasma, membrane, and, is, required, for, the, production, of, 'NOX-generated', 'ROS'])]). relacion([sujeto(['Many', assays]), verbo([have]), complemento([been, developed, for, the, detection, of, influenza, virus, which, is, an, important, respiratory, pathogen])]). relacion([sujeto(['Development', of, these, assays, commonly]), verbo([involves]), complemento([the, use, of, human, clinical, samples, for, validation, of, their, performance])]). relacion([sujeto(['The', goal, of, this, study, was, to, develop, a, simulated, respiratory, secretion, '(', 'SRS)', that, could]), verbo([act]), complemento([as, a, surrogate, for, clinical, samples])]). relacion([sujeto(['To', this, 'end,', we, determined, the, effects, major, respiratory, secretion, components, '(', 'Na+,', 'K+,', 'Ca2+,', 'cells,', albumin, 'IgG,', 'IgM,', and, 'mucin)']), verbo([have]), complemento([on, the, performance, of, influenza, assays, including, both, nucleic, acid, amplification, and, rapid, antigen, assays])]). relacion([sujeto(['Minimal', effects, on, the, molecular, assays, were, observed, for, all, of, the, components, 'tested,', except, for, serum, derived, human, 'IgG,', which]), verbo([suppressed]), complemento([the, signal, of, the, rapid, antigen, assays])]). relacion([sujeto(['Our', results, demonstrated, that, a, 'SRS', can]), verbo([interact]), complemento([with, a, variety, of, test, methods, in, a, similar, manner, to, clinical, samples, with, a, similar, impact, on, test, performance])]). relacion([sujeto(['Dendritic', cells, play, a, crucial, role, in, the, link, between, innate, and, adaptive, immune, response, and, orchestrating, the, 'T-cell', response, and, are, implicated, in, the, severe, inflammatory, process]), verbo([found]), complemento([in, nasal, polypoid, tissue])]). relacion([sujeto(['Dendritic', cells, are]), verbo([found]), complemento([increased, in, nasal, 'polyposis,', regardless, of, subset])]). relacion([sujeto(['Of', 'interest,', plasmacytoid, dendritic, cells, are]), verbo([decreased]), complemento([in, patients, with, a, more, severe, 'Th2', 'profile,', suggesting, an, important, role, of, the, cytokines, milieu, in, their, functional, response, or, that, plasmacytoid, dendritic, cell, could, act, mitigating, the, inflamed, process, found, in, polypoid, tissue])]). relacion([sujeto(['This', inequality]), verbo([leads]), complemento([to, 'male-specific', effects, of, the, 'Y', 'chromosome,', including, expression, of, the, 'testis-determining', gene, 'Sry', that, causes, differentiation, of, testes])]). relacion([sujeto(['Y', genes, also]), verbo([act]), complemento([outside, of, the, gonads, to, cause, 'male-specific', effects])]). relacion([sujeto(['Differences', in, the, number, of, 'X', chromosomes, between, 'XX', and, 'XY', cells]), verbo([cause]), complemento([sex, differences, in, expression, '(', 1, ')', of, 'Xist,', '(', 2, ')', of, 'X', genes, that, escape, 'inactivation,', and, '(', 3, ')', of, parentally, imprinted, 'X', genes])]). relacion([sujeto(['These', factors]), verbo([act]), complemento([in, parallel, and, in, combination, to, induce, sex, differences])]). relacion([sujeto(['Other', 'mechanisms,', operating, at, the, level, of, 'populations,']), verbo([cause]), complemento([groups, of, males, to, differ, on, average, from, groups, of, females])]). relacion([sujeto(['The', theory, frames, questions, for, further, 'study,', and, directs, attention, to, inherent, 'sex-biasing', factors, that, operate, in, many, tissues, to]), verbo([cause]), complemento([sex, 'differences,', and, to, cause, 'sex-biased', protection, from, disease])]). relacion([sujeto(['Sex', hormones]), verbo([act]), complemento([throughout, the, entire, brain, of, both, males, and, females, via, both, genomic, and, nongenomic, receptors])]). relacion([sujeto(['Sex', hormones, can]), verbo([act]), complemento([through, many, cellular, and, molecular, processes, that, alter, structure, and, function, of, neural, systems, and, influence, behavior, as, well, as, providing, neuroprotection])]). relacion([sujeto(['Within', 'neurons,', sex, hormone, receptors, are]), verbo([found]), complemento([in, nuclei, and, are, also, located, near, 'membranes,', where, they, are, associated, with, presynaptic, 'terminals,', 'mitochondria,', spine, 'apparatus,', and, postsynaptic, densities])]). relacion([sujeto(['Sex', hormone, receptors, also, are]), verbo([found]), complemento([in, glial, cells])]). relacion([sujeto(['Hormonal', regulation, of, a, variety, of, signaling, pathways, as, well, as, direct, and, indirect, effects, on, gene, expression]), verbo([induce]), complemento([spine, 'synapses,', 'up-', or, downregulate, and, alter, the, distribution, of, neurotransmitter, 'receptors,', and, regulate, neuropeptide, expression, and, cholinergic, and, 'GABAergic', activity, as, well, as, calcium, sequestration, and, oxidative, stress])]). relacion([sujeto(['These', sex, differences, and, responses, to, sex, hormones, in, brain, 'regions,', which, influence, functions, not, previously, regarded, as, subject, to, such, 'differences,', indicate, that, we, are, entering, a, new]), verbo([era]), complemento([of, our, ability, to, understand, and, appreciate, the, diversity, of, 'gender-related', behaviors, and, brain, functions])]). relacion([sujeto([elegans]), verbo([have]), complemento([provided, unique, insights, into, the, development, and, function, of, sex, differences, in, the, nervous, system])]). relacion([sujeto(['Enabled', by, the, relative, simplicity, of, this, 'species,', comprehensive, studies]), verbo([have]), complemento([solved, the, complete, cellular, neuroanatomy, of, both, sexes, as, well, as, the, complete, neural, connectomes, of, the, entire, adult, hermaphrodite, and, the, adult, male, tail])]). relacion([sujeto(['This', 'work,', together, with, detailed, behavioral, 'studies,']), verbo([has]), complemento([revealed, three, aspects, of, sex, differences, in, the, nervous, 'system:', 'sex-specific', neurons, and, 'circuits;', circuits, with, sexually, dimorphic, synaptic, 'connectivity;', and, sex, differences, in, the, physiology, and, functions, of, shared, neurons, and, circuits])]). relacion([sujeto(['At', all, of, these, 'levels,', biological, sex, influences, neural, development, and, function, through, the, activity, of, a, 'well-defined', genetic, hierarchy, that]), verbo([acts]), complemento([throughout, the, body, to, translate, chromosomal, sex, into, the, state, of, a, master, autosomal, regulator, of, sexual, 'differentiation,', the, transcription, factor, 'TRA-1A'])]). relacion([sujeto(['An', important, and, unexpected]), verbo([finding]), complemento([from, these, studies, is, that, chemosensory, neurons, are, a, primary, focus, of, sexual, 'modulation,', with, genetic, sex, adaptively, shaping, chemosensory, repertoire, to, guide, behavioral, choice])]). relacion([sujeto(['Importantly,', 'hormone-independent', functions, of, genetic, sex, are, the, principal, drivers, of, all, of, these, sex, 'differences,', making, nematodes, an, excellent, model, for, understanding, similar, but, poorly, understood, mechanisms, that, likely]), verbo([act]), complemento([throughout, the, animal, kingdom])]). relacion([sujeto(['One', of, its, main, advantages, is, that, score, generation]), verbo([involves]), complemento([summation, of, clinical, parameters, that, are, available, pretransplant])]). relacion([sujeto(['However,', the, 'EBMT', risk, score, is]), verbo([recognized]), complemento([as, not, being, optimal])]). relacion([sujeto(['Previous', 'analyses,']), verbo([involving]), complemento([patients, with, various, 'diagnoses,', have, shown, that, 'non-HLA', gene, polymorphisms, influence, outcome, after, allogeneic, 'HSCT'])]). relacion([sujeto(['The', results, of, the, study]), verbo([found]), complemento([that, three, genetic, factors, improved, 'EBMT', risk, score])]). relacion([sujeto(['The', presence, of, 'MAL', '(', 'rs8177374)', allele, 'T', in, the, 'patient,', absence, of, glucocorticoid, receptor, haplotype, '(', consisting, of, 'rs6198,', rs33389, and, 'rs33388)', 'ACT', in, the, patient, and, absence, of, 'heat-shock', protein, 70, -, hom, '(', +, 2437, ')', '(', 'rs2227956)', allele, 'C', in, the, patient, were]), verbo([associated]), complemento([with, decreased, survival, time])]). relacion([sujeto(['A', bootstrapping, 'technique,']), verbo([involving]), complemento([repeated, testing, of, a, model, using, multiple, validation, 'sets,', also, revealed, that, the, newly, proposed, model, had, improved, predictive, value, when, compared, to, the, 'EBMT', risk, score, alone])]). relacion([sujeto(['Results', support, the, view, that, 'non-HLA', polymorphisms, could, be, useful, for, pretransplant, clinical, assessment, and]), verbo([provide]), complemento([evidence, that, polymorphisms, in, the, recipient, genotype, may, influence, incoming, donor, 'cells,', suppressing, the, initiation, of, the, graft, versus, leukaemia, effect, and, reducing, survival])]). relacion([sujeto(['With', the, working, hypothesis, that, tooth, and, jaw, development, are, autonomously, controlled, by, discreet, gene, regulatory, 'networks,', using, gene, expression, microarray, assays, validated, by, quantitative, 'reverse-transcription', 'PCR', we, contrasted, expression, in, mandibular, prominences, at, embryonic, days, '(', 'E)', 10, -, 13, of, mice, with, normal, lower, jaw, development, but, either, normal, '(', 'p63(+/-)', ',', 'p63(+/+)', ')', or]), verbo([arrested]), complemento(['(', 'p63(-/-)', ')', tooth, development])]). relacion([sujeto(['Some', of, these, are, known, to, help]), verbo([regulate]), complemento([odontogenesis, '(', e])]). relacion([sujeto([',', 'p63,', 'Osr2,', 'Cldn3/4)', 'and/or', to, be]), verbo([targets]), complemento([of, p63, '(', e])]). relacion([sujeto([',', 'Jag1/2,', 'Fgfr2);', other, genes]), verbo([have]), complemento([no, previously, reported, roles, in, odontogenesis, or, the, p63, pathway, '(', e])]). relacion([sujeto(['As', 'expected,', from, 'E10', to, 'E13,', few, genes, known, to]), verbo([regulate]), complemento([mandible, morphogenesis, differed, in, expression, between, mouse, strains])]). relacion([sujeto(['We', propose, that, these, genes]), verbo([act]), complemento([in, a, novel, odontogenic, network, that, is, exclusive, of, lower, jaw, 'morphogenesis,', and, posit, that, this, network, evolved, in, 'oral,', not, 'pharyngeal,', teeth])]). relacion([sujeto(['Decades', of, ecological, study]), verbo([have]), complemento([demonstrated, the, importance, of, 'top-down', and, 'bottom-up', controls, on, food, 'webs,', yet, few, studies, within, this, context, have, quantified, the, magnitude, of, energy, and, material, fluxes, at, the, 'whole-ecosystem', scale])]). relacion([sujeto(['We', examined, 'top-down', and, 'bottom-up', effects, on, food, web, fluxes, using, a, field, experiment, that, manipulated, the, presence, of, a, 'consumer,', the, 'Trinidadian', guppy, 'Poecilia', 'reticulata,', and, the, production, of, basal, resources, by, thinning, the, riparian, forest, canopy, to]), verbo([increase]), complemento([incident, light])]). relacion([sujeto(['The', thinned, canopy, stream, had, higher, primary, production, than, the, natural, canopy, 'control,']), verbo([leading]), complemento([to, increased, 'N', fluxes, to, invertebrates, that, feed, on, benthic, biofilms, '(', 'grazers),', fine, benthic, organic, matter, '(', 'collector-gatherers),', and, organic, particles, suspended, in, the, water, column, '(', filter, 'feeders)'])]). relacion([sujeto(['N', fluxes, to, 'leaf-shredding', 'invertebrates,', predatory, 'invertebrates,', and, the, other, fish, species, present, '(', 'Hart\'s', 'killifish,', 'Anablepsoides', 'hartii)', did, not, differ, across, light, or, guppy, 'treatments,']), verbo([suggesting]), complemento([that, effects, on, 'detritus-based', linkages, and, upper, trophic, levels, were, not, as, strong])]). relacion([sujeto(['Combined,', these, results, extend, previous, knowledge, about, 'top-down', and, 'bottom-up', controls, on, ecosystems, by]), verbo([providing]), complemento(['experimental,', 'reach-scale', evidence, that, both, pathways, can, act, simultaneously, and, have, equally, strong, influence, on, nutrient, fluxes, from, inorganic, pools, through, primary, consumers])]). relacion([sujeto(['The', majority, of, humanity, now, lives, in, cities, or, 'towns,', with, this, proportion, expected, to, continue]), verbo([increasing]), complemento([for, the, foreseeable, future])]). relacion([sujeto(['As', novel, 'ecosystems,', urban, areas, offer, an, ideal, opportunity, to, examine, 'multi-scalar', processes]), verbo([involved]), complemento([in, community, assembly, as, well, as, the, role, of, human, activities, in, modulating, environmental, drivers, of, biodiversity])]). relacion([sujeto(['Although', ecologists]), verbo([have]), complemento([made, great, strides, in, recent, decades, at, documenting, ecological, relationships, in, urban, 'areas,', much, remains, 'unknown,', and, we, still, need, to, identify, the, major, ecological, 'factors,', aside, from, habitat, 'loss,', behind, the, persistence, or, extinction, of, species, and, guilds, of, species, in, cities])]). relacion([sujeto(['In', addition, to, these, 'filters,', life, history, and, functional, traits, of, species, are, important, in, determining, community, assembly, and]), verbo([act]), complemento([at, multiple, spatial, scales])]). relacion([sujeto(['This', points, to, the, utility, of]), verbo([targeting]), complemento([parental, psychological, flexibility, in, pediatric, chronic, pain])]). relacion([sujeto(['The', 'Parent', 'Psychological', 'Flexibility', 'Questionnaire', '(', 'PPFQ)', is, currently, the, only, instrument, developed, for, this, 'purpose,', and, two, previous, studies]), verbo([have]), complemento([indicated, its, reliability, and, validity])]). relacion([sujeto(['In', 'conclusion,', results, support, the, reliability, and, validity, of, the, 'PPFQ-10,', and]), verbo([suggest]), complemento([its, usefulness, in, assessing, psychological, flexibility, in, parents, of, children, with, chronic, pain])]). relacion([sujeto(['In', the, present, 'study,', we]), verbo([reported]), complemento([the, cytotoxicity, of, toosendanin, '(', 'TSN)', in, the, 'GBM', 'U87', and, 'C6', cell, lines, in, vitro, and, in, vivo])]). relacion([sujeto(['By', using, the, 'MTT', '(', 3, -, '(', 4, ',', 5, -, 'dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium', 'bromide)', 'assay,', flow, cytometry, 'analysis,', and, 'Western', 'blot,', we]), verbo([found]), complemento([that, 'TSN', inhibited, 'U87', and, 'C6', cell, proliferation, and, induced, apoptosis, at, a, concentration, as, low, as, 10, nM])]). relacion([sujeto(['Pharmacological', and, molecular, studies]), verbo([suggested]), complemento([that, estrogen, receptor, β, '(', 'ERβ)', and, p53, were, prominent, targets, for, 'TSN'])]). relacion([sujeto(['GBM', cell, apoptosis]), verbo([induced]), complemento([by, 'TSN', was, a, stepwise, biological, event, involving, the, upregulation, of, 'ERβ', and, contextual, activation, of, functional, p53])]). relacion([sujeto(['Furthermore,', 'ERβ', and, p53, could]), verbo([act]), complemento([as, predictive, biomarkers, for, the, sensitivity, of, cancer, to, 'TSN'])]). relacion([sujeto(['The', challenge, thus]), verbo([involves]), complemento([maximizing, the, potential, for, normal, growth, without, increasing, the, risk, of, associated, disorders])]). relacion([sujeto(['The', articular, surfaces, and, menisci]), verbo([act]), complemento([with, the, anterior, cruciate, ligament, '(', 'ACL)', to, stabilize, the, knee, joint])]). relacion([sujeto(['In', response, to, applied, valgus, and, internal, rotation, torques, in, the, absence, of, 'compression,', sectioning, of, the, 'ACL']), verbo([increased]), complemento([the, net, force, carried, by, the, lateral, meniscus, by, at, most, 65.8, 'N', '(', p, &, 'lt;', 0.001, ')'])]). relacion([sujeto(['Moreover,', the, anterior, shear, force, carried, by, the, lateral, meniscus]), verbo([increased]), complemento([by, 25.7, 'N', '(', p, &, 'lt;', 0.001, ')', and, 36.5, 'N', '(', p, =, 0.042, ')', in, the, absence, and, presence, of, 'compression,', respectively])]). relacion([sujeto(['In', response, to, applied, valgus, and, internal, rotation, 'torques,', sectioning, of, the, 'ACL']), verbo([increased]), complemento([the, net, force, carried, by, 'cartilage-to-cartilage', contact, on, the, medial, femoral, condyle, by, at, most, 38.9, 'N', '(', p, =, 0.006, ')', and, 46.7, 'N', '(', p, =, 0.04, ')', in, the, absence, and, presence, of, 'compression,', respectively])]). relacion([sujeto(['Additionally,', the, lateral, shear, force, carried, by, 'cartilage-to-cartilage', contact, on, the, medial, femoral, condyle]), verbo([increased]), complemento([by, at, most, 21.0, 'N', '(', p, =, 0.005, ')', and, by, 28.0, 'N', '(', p, =, 0.025, ')', in, the, absence, and, presence, of, 'compression,', respectively])]). relacion([sujeto(['ACL', sectioning]), verbo([increased]), complemento([the, net, forces, carried, by, the, lateral, meniscus, and, medial, femoral, 'condyle-and', the, anterior, shear, and, lateral, shear, 'forces,', 'respectively-in', response, to, multiplanar, valgus, and, internal, rotation, torque])]). relacion([sujeto(['These', loading, patterns]), verbo([provide]), complemento([a, biomechanical, rationale, for, clinical, patterns, of, 'intra-articular', derangement, such, as, lateral, meniscal, injury, and, osseous, remodeling, of, the, medial, compartment, seen, with, 'ACL', insufficiency])]). relacion([sujeto(['Birds', in, the, treatment, group, were]), verbo([provided]), complemento([the, same, diet, supplemented, with, 2, 'g/kg', 'BA', encapsulated, in, a, vegetable, oil, matrix])]). relacion([sujeto(['BA', concentration]), verbo([decreased]), complemento([rapidly, in, the, proximal, gut])]). relacion([sujeto(['Caecal', total, and, branched, chain, fatty, acids, were]), verbo([decreased]), complemento([due, to, the, treatment])]). relacion([sujeto(['A', trend, for]), verbo([increased]), complemento([lactobacilli, was, observed, in, the, 'crop,', while, it, became, significant, in, the, jejunum, and, ileum])]). relacion([sujeto(['Lactobacillus', species]), verbo([responded]), complemento([differently, to, the, treatment])]). relacion([sujeto(['Clostridial', clusters, 'IV', and, 'XIVa', were, significantly]), verbo([increased]), complemento([in, the, 'jejunum,', whereas, only, clostridial, cluster, 'XIVa', was, increased, in, the, caecum])]). relacion([sujeto(['Encapsulated', 'BA', modified, the, intestinal, microbiota, which, can]), verbo([lead]), complemento([to, the, 'conclusion,', that, the, main, beneficial, mode, of, action, of, 'BA', in, the, gut, appears, to, be, the, enhancement, of, lactic, acid, 'bacteria,', which, in, turn, may, act, as, a, vanguard, against, pathogens])]). relacion([sujeto(['The', 'three-membered', 'RUNX', gene, family, includes, 'RUNX1,', a, major, mutational]), verbo([target]), complemento([in, human, 'leukemias,', and, displays, hallmarks, of, both, tumour, suppressors, and, oncogenes])]). relacion([sujeto(['In', mouse, models, the, 'Runx', genes, appear, to]), verbo([act]), complemento([as, conditional, 'oncogenes,', as, ectopic, expression, is, growth, suppressive, in, normal, cells, but, drives, lymphoma, development, potently, when, combined, with, 'over-expressed', 'Myc', or, loss, of, p53])]). relacion([sujeto(['Clues', to, underlying, mechanisms, emerged, previously, from, murine, fibroblasts, where, ectopic, expression, of, any, of, the, 'Runx', genes]), verbo([promotes]), complemento([survival, through, direct, and, indirect, regulation, of, key, enzymes, in, sphingolipid, metabolism, associated, with, a, shift, in, the, '\'', sphingolipid, 'rheostat\'', from, ceramide, to, 'sphingosine-1-phosphate', '(', 'S1P)'])]). relacion([sujeto(['We']), verbo([find]), complemento([that, ectopic, expression, of, 'Runx1', in, lymphoma, cells, consistently, perturbs, the, sphingolipid, 'rheostat,', while, an, essential, physiological, role, for, 'Runx1', is, revealed, by, reduced, 'S1P', levels, in, normal, spleen, after, partial, 'Cre-mediated', excision])]). relacion([sujeto(['Furthermore', we, show, that, ectopic, 'Runx1', expression]), verbo([confers]), complemento([increased, resistance, of, lymphoma, cells, to, 'glucocorticoid-mediated', 'apoptosis,', and, elucidate, the, mechanism, of, 'cross-talk', between, glucocorticoid, and, sphingolipid, metabolism, through, 'Sgpp1'])]). relacion([sujeto(['Dexamethasone', potently]), verbo([induces]), complemento([expression, of, 'Sgpp1', in, 'T-lymphoma', cells, and, drives, cell, death, which, is, reduced, by, partial, knockdown, of, 'Sgpp1', with, shRNA, or, direct, transcriptional, repression, of, 'Sgpp1', by, ectopic, 'Runx1'])]). relacion([sujeto(['Together', these, data, show, that, 'Runx1', plays, a, role, in]), verbo([regulating]), complemento([the, sphingolipid, rheostat, in, normal, development, and, that, perturbation, of, this, cell, fate, regulator, contributes, to, 'Runx-driven', lymphomagenesis])]). relacion([sujeto(['The', expression, profiles, of, two]), verbo([target]), complemento([genes, '(', 'EYA', and, 'HHEX)', in, thirteen, developmental, stages, were, used, to, confirm, the, reliability, of, chosen, 'RGs'])]). relacion([sujeto(['Neurofeedback-guided', motor, imagery, training, '(', 'NF-MIT)']), verbo([has]), complemento([been, suggested, as, a, promising, therapy, for, 'stroke-induced', motor, impairment])]). relacion([sujeto(['Whereas', much, 'NF-MIT', research]), verbo([has]), complemento([aimed, at, signal, processing, 'optimization,', the, type, of, sensory, feedback, given, to, the, participant, has, received, less, attention])]). relacion([sujeto(['Often', the, feedback, signal, is, highly, abstract, and, not, inherently, coupled, to, the, mental]), verbo([act]), complemento([performed])]). relacion([sujeto(['Inspired', by, the, rubber, hand, 'illusion,', demonstrating, that, an, artificial, hand, can, be, incorporated, into, 'one\'s', own, body, 'scheme,', we, used, an, anthropomorphic, robotic, hand, to, visually, guide, the, 'participants\'', motor, imagery]), verbo([act]), complemento([and, to, deliver, neurofeedback])]). relacion([sujeto(['As', pertains, to, 'embodiment,', we]), verbo([found]), complemento([a, promoting, effect, of, 'robotic-hand', embodiment, in, 'subjective,', 'behavioral,', electrophysiological, and, electrodermal, measures])]). relacion([sujeto(['Regarding', neurofeedback, signal, 'validity,', we]), verbo([found]), complemento([some, differences, between, real, and, sham, neurofeedback, in, terms, of, subjective, and, electrodermal, 'measures,', but, not, in, terms, of, behavioral, and, electrophysiological, measures])]). relacion([sujeto(['Mechanisms']), verbo([regulating]), complemento([the, transition, of, mammary, epithelial, cells, '(', 'MECs)', to, mammary, stem, cells, '(', 'MaSCs)', and, to, 'tumor-initiating', cells, '(', 'TICs)', have, not, been, entirely, elucidated])]). relacion([sujeto(['The', p53, family, 'member,', 'p63,', is, critical, for, mammary, gland, development, and, contains, transactivation, domain, 'isoforms,', which]), verbo([have]), complemento(['tumor-suppressive', 'activities,', and, the, 'ΔN', 'isoforms,', which, act, as, oncogenes])]). relacion([sujeto(['Loss', of, 'TAp63', in, mice]), verbo([leads]), complemento([to, the, formation, of, aggressive, metastatic, mammary, adenocarcinoma, at, 9, -, 16, months, of, age])]). relacion([sujeto(['When', 'TAp63', is, 'lost,', 'MECs']), verbo([express]), complemento([embryonic, and, 'MaSC', signatures, and, activate, the, 'Hippo', pathway])]). relacion([sujeto(['These', data, indicate, a, crucial, role, for, 'TAp63', in, mammary, 'TICs', and]), verbo([provide]), complemento([a, mechanism, for, its, role, as, a, 'tumor-', and, 'metastasis-suppressor', in, breast, cancer])]). relacion([sujeto(['Determining', and]), verbo([acting]), complemento([on, 'thermo-physical', properties, at, the, nanoscale, is, essential, for, 'understanding/managing', heat, distribution, in, 'micro/nanostructured', materials, and, miniaturized, devices])]). relacion([sujeto(['Adequate', thermal, 'nano-characterization', techniques, are]), verbo([required]), complemento([to, address, thermal, issues, compromising, device, performance])]). relacion([sujeto(['Scanning', thermal, microscopy, '(', 'SThM)', is, a, probing, and]), verbo([acting]), complemento([technique, based, on, atomic, force, microscopy, using, a, 'nano-probe', designed, to, act, as, a, thermometer, and, resistive, 'heater,', achieving, high, spatial, resolution])]). relacion([sujeto(['Finally,', an, approach, to]), verbo([induce]), complemento([and, study, local, structural, transitions, in, ferromagnetic, shape, memory, alloy, 'Ni-Mn-Ga', thin, films, using, localized, 'nano-thermal', analysis, is, presented])]). relacion([sujeto([23, ')', but, did, not]), verbo([act]), complemento([as, a, risk, factor])]). relacion([sujeto(['Patients', with, high, 'BMI', were, inclined, to]), verbo([have]), complemento([better, overall, survival, '(', 'OS)', '(', p, =])]). relacion([sujeto([18, ')', ',', but, we, 'didn\'t']), verbo([find]), complemento([an, association, in, 'progression-free', survival, '(', 'PFS)', '(', p, =])]). relacion([sujeto(['We', also]), verbo([found]), complemento([a, 'sex-dependent', effect, of, 'BMI', on, 'OS,', with, high, 'BMI', increased, 'OS', in, female, patients, '(', p, =])]). relacion([sujeto(['Fungi', of, the, 'Pucciniales', order]), verbo([cause]), complemento([rust, 'diseases,', which, altogether, affect, thousands, of, plant, species, worldwide, and, pose, major, threat, to, several, crops])]). relacion([sujeto(['How', rust, effectors, -, virulence, proteins, delivered, into, infected, tissues, to]), verbo([modulate]), complemento([host, functions, -, contribute, to, pathogen, virulence, remains, poorly, understood])]). relacion([sujeto(['Melampsora', 'larici-populina', is, a, devastating, and, widespread, rust, pathogen, of, poplars, and, its, genome, encodes, 1, ',', 184, identified, small, secreted, proteins, that, could, potentially]), verbo([act]), complemento([as, effectors])]). relacion([sujeto(['Infection', assays, using, bacterial, '(', 'Pseudomonas', 'syringae)', and, oomycete, '(', 'Hyaloperonospora', 'arabidopsidis)', pathogens, revealed, subsets, of, candidate, effectors, that]), verbo([enhanced]), complemento([or, decreased, pathogen, leaf, colonization])]). relacion([sujeto(['Confocal', imaging, of, 'GFP-tagged', candidate, effectors, constitutively]), verbo([expressed]), complemento([in, stable, transgenic, plants, revealed, that, some, protein, fusions, specifically, accumulate, in, 'nuclei,', 'chloroplasts,', plasmodesmata, and, punctate, cytosolic, structures])]). relacion([sujeto(['Altogether,', our, analysis]), verbo([suggests]), complemento([that, rust, fungal, candidate, effectors, target, distinct, cellular, components, in, host, cells, to, promote, parasitic, growth])]). relacion([sujeto(['Despite', extensive, research, exploring, alcohol, advertising, and, sponsorship, through, 'sport,', minimal, attention]), verbo([has]), complemento([been, given, to, digital, platforms])]). relacion([sujeto(['Four', 'sport-related', social, media, strategies, are, identified, through, which, alcohol, brands, solicit, interaction, with, 'consumers,', often]), verbo([involving]), complemento(['co-creation', of, content, and, social, activation])]). relacion([sujeto(['These', strategies]), verbo([act]), complemento([as, '\'', calls, to, 'action\'', and, through, the, association, of, sport, and, alcohol, encourage, consumers, to, engage, in, 'competition,', 'collaboration,', celebration, and, consumption])]). relacion([sujeto(['Sport-linked', social, media, strategies, utilised, by, alcohol, brands, extend, beyond, just]), verbo([promoting]), complemento([their, product])]). relacion([sujeto(['The', discussion, highlights, the, powerful, combination, of, sport, and, social, media, as, a, mechanism, by, which, these, brands, seek, to]), verbo([interact]), complemento([with, consumers, and, encourage, them, to, both, create, and, promote, content, to, their, social, networks])]). relacion([sujeto(['To', examine, changes, in, 'children\'s', albuterol, use, and, 'out-of-pocket', '(', 'OOP)', costs, in, response, to]), verbo([increased]), complemento([copayments, after, the, 'Food', and, 'Drug', 'Administration', banned, inhalers, with, chlorofluorocarbon, '(', 'CFC)', propellants])]). relacion([sujeto(['Four', health, maintenance, organizations, '(', 'HMOs),', two, that]), verbo([increased]), complemento([copayments, for, albuterol, inhalers, that, went, from, generic, 'CFC-containing', to, branded, 'CFC-free', 'versions,', and, two, that, retained, generic, copayments, for, 'CFC-free', inhalers, '(', 'controls)'])]). relacion([sujeto(['There', were, no, significant, differences, in, albuterol, use, between, the, group, with]), verbo([increased]), complemento(['cost-sharing', and, controls, with, respect, to, changes, after, the, policy, change])]). relacion([sujeto(['There', was, a, postpolicy]), verbo([increase]), complemento([of, '$6'])]). relacion([sujeto([11, 'OOP', per, month, per, child, using, albuterol, among, those, with]), verbo([increased]), complemento(['cost-sharing', versus, '$0'])]). relacion([sujeto(['Increased', copayments, for, 'brand-name', 'CFC-free', albuterol, after, the, 'CFC', ban, did, not]), verbo([lead]), complemento([to, a, decrease, in, 'children\'s', albuterol, 'use,', but, it, led, to, a, modest, increase, in, 'OOP', costs])]). relacion([sujeto(['Four', new, ruthenium, arene, 'PTA', type, complexes]), verbo([have]), complemento([been, synthesized, using, substituted, picolinamide, derivatives, as, ancillary, ligands, and, characterized, by, spectroscopic, methods])]). relacion([sujeto(['In', one, of, the, 'complexes,', the, ancillary, ligand]), verbo([has]), complemento([shown, an, unprecedented, 'valence-bond', tautomerization, in, the, presence, of, an, ammonium, salt, to, act, as, a, polar, neutral, donor, ligand, making, the, ligand, more, prone, towards, substitution])]). relacion([sujeto(['The', same, compound]), verbo([has]), complemento([shown, remarkable, antiproliferative, activity, against, three, cancer, cell, lines, with, 'GI50', values, comparable, to, 'Adriamycin,', a, known, therapeutic, drug])]). relacion([sujeto(['Along', with, this, it, also, strongly]), verbo([inhibits]), complemento([the, action, of, thioredoxin, 'reductase,', which, might, be, a, probable, reason, for, the, enhanced, proliferative, action, of, the, 'valence-bond', tautomerized, compound])]). relacion([sujeto(['The', corticostriatothalamic, circuit]), verbo([regulates]), complemento([learning, behaviors, via, dopamine, neurotransmission])]). relacion([sujeto(['D2', long, '(', 'D2L)', receptors, are, an, isoform, of, dopamine, 'D2', receptors, '(', 'D2Rs)', and, may]), verbo([act]), complemento([mainly, at, postsynaptic, sites])]). relacion([sujeto(['More', than, a, 'decade,', overlapping, genes, in, 'RNA', viruses, became, a, subject, of, research, which]), verbo([has]), complemento([explored, various, effect, of, gene, overlapping, on, the, evolution, and, function, of, viral, genomes, like, genome, size, compaction])]). relacion([sujeto(['Additionally,', overlapping, regions, '(', 'OVRs)', are, also]), verbo([reported]), complemento([to, encode, elevated, degree, of, protein, intrinsic, disorder, '(', 'PID)', in, unspliced, 'RNA', viruses])]). relacion([sujeto(['With', the, aim, to, explore, the, roles, of, 'OVRs', in, 'HIV-1', 'pathogenesis,', we]), verbo([have]), complemento([carried, out, an, 'in-depth', analysis, on, the, association, of, gene, overlapping, with, 'PID', in, 35, 'HIV1-', 'M', subtypes])]). relacion([sujeto(['Our', study]), verbo([reveals]), complemento([an, over, representation, of, 'PID', in, 'OVR', of, 'HIV-1', genomes])]). relacion([sujeto(['These', disordered, residues, endure, several, 'vital,', structural, features, like, short, linear, motifs, '(', 'SLiMs)', and, protein, phosphorylation, '(', 'PP)', sites, which, are, previously, shown, to, be]), verbo([involved]), complemento([in, massive, 'host-virus', interaction])]). relacion([sujeto(['Although,', density, of, experimentally, verified, 'SLiMs,', resided, in, 9, 'HIV-1', 'genes,']), verbo([involved]), complemento([in, 'host-virus', interaction, do, not, show, any, bias, toward, clustering, into, 'OVR,', tat, and, rev, two, important, proteins, mediates, 'host-pathogen', interaction, by, their, experimentally, verified, 'SLiMs,', which, are, mostly, localized, in, 'OVR'])]). relacion([sujeto(['Finally,', our, analysis]), verbo([suggests]), complemento([that, the, acquisition, of, 'SLiMs', in, 'OVR', is, mutually, exclusive, of, the, occurrence, of, disordered, 'residues,', while, the, enrichment, of, 'PPs', in, 'OVR', is, solely, dependent, on, 'PID', and, not, on, overlapping, coding, frames])]). relacion([sujeto(['Prostaglandin', 'reductase-1', '(', 'Ptgr1)', is, an, 'alkenal/one', oxidoreductase, that, is]), verbo([involved]), complemento([in, the, catabolism, of, eicosanoids, and, lipid, peroxidation, such, as, 4, -, hydroxynonenal, '(', 4, -, 'HNE)'])]). relacion([sujeto(['Recently,', we]), verbo([reported]), complemento([that, 'Ptgr1', is, overexpressed, in, human, clinical, and, experimentally, induced, samples, of, hepatocellular, carcinoma, '(', 'HCC)'])]). relacion([sujeto(['However,', how, the, expression, of, this, gene, is]), verbo([regulated]), complemento([and, its, role, in, carcinogenesis, are, not, yet, known])]). relacion([sujeto(['Here,', we, studied, parameters]), verbo([associated]), complemento([with, antioxidant, responses, and, the, mechanisms, underlying, the, induction, of, 'Ptgr1', expression, by, the, activation, of, 'Nuclear', 'Factor', '(', 'erythroid-derived-2)-like-2', '(', 'NRF2)'])]). relacion([sujeto(['For', these, 'experiments,', we, used, two, protocols, of]), verbo([induced]), complemento([hepatocarcinogenesis, in, rats])]). relacion([sujeto(['Ptgr1', was, overexpressed, during, the, early, phase, in, altered, hepatocyte, 'foci,', and, this, high, level, of, expression, was]), verbo([maintained]), complemento([in, persistent, nodules, until, tumors, developed])]). relacion([sujeto(['Ptgr1', expression, was]), verbo([regulated]), complemento([by, 'NRF2,', which, bound, to, an, antioxidant, response, element, at, -, 653, bp, in, the, rat, 'Ptgr1', gene])]). relacion([sujeto(['The', activation, of, 'NRF2']), verbo([induced]), complemento([the, activation, of, an, antioxidant, response, that, included, effects, on, proteins, such, as, 'glutamate-cysteine', 'ligase,', catalytic, 'subunit,', 'NAD(P)H', dehydrogenase, 'quinone-1', '(', 'NQO1)', and, 'glutathione-S-transferase-P', '(', 'GSTP1)'])]). relacion([sujeto(['These', effects, may]), verbo([have]), complemento([produced, a, reduced, status, that, was, associated, with, a, high, proliferation, rate, in, experimental, tumors])]). relacion([sujeto(['Indeed,', when, 'Ptgr1', was, stably, 'expressed,', we, observed, a, reduction, in, the, time]), verbo([required]), complemento([for, proliferation, and, a, protective, effect, against, hydrogen, 'peroxide-', and, 4, -, 'HNE-induced', cell, death])]). relacion([sujeto(['These', findings]), verbo([suggest]), complemento([that, 'Ptgr1', and, antioxidant, responses, act, as, a, metabolic, adaptation, and, could, contribute, to, proliferation, and, 'cell-death', evasion, in, liver, tumor, cells])]). relacion([sujeto(['Furthermore,', these, data, indicate, that, 'Ptgr1', could, be, used, to, design, early, diagnostic, tools, or]), verbo([targeted]), complemento([therapies, for, 'HCC'])]). relacion([sujeto(['Gene', expression, often]), verbo([requires]), complemento([interaction, between, promoters, and, distant, 'enhancers,', which, occur, within, the, context, of, highly, organized, topologically, associating, domains, '(', 'TADs)'])]). relacion([sujeto(['We', show, that, 'Shh', enhancers]), verbo([act]), complemento(['pervasively,', yet, not, 'uniformly,', throughout, the, 'TAD'])]). relacion([sujeto(['In', 'contrast,', inversions, disrupting, the, 'TAD', altered, global, folding, of, the, region, and]), verbo([prevented]), complemento([regulatory, contacts, in, a, 'distance-dependent', manner])]). relacion([sujeto(['Our', data, indicate, that, the, 'Shh', 'TAD']), verbo([promotes]), complemento(['distance-independent', contacts, between, distant, regions, that, would, otherwise, interact, only, 'sporadically,', enabling, functional, communication, between, them])]). relacion([sujeto(['The', 'ERK-regulated', ternary, complex, factors, '(', 'TCFs)']), verbo([act]), complemento([with, the, transcription, factor, serum, response, factor, '(', 'SRF)', to, activate, 'mitogen-induced', transcription])]). relacion([sujeto(['However,', the, extent, of, their, involvement, in, the, 'immediate-early', transcriptional, 'response,', and, their, wider, functional, 'significance,']), verbo([has]), complemento([remained, unclear])]). relacion([sujeto(['We', show, 'that,', in, 'MEFs,', 'TCF', inactivation, significantly]), verbo([inhibits]), complemento([over, 60, '%', of, 'TPA-inducible', gene, transcription, and, impairs, cell, proliferation])]). relacion([sujeto(['Using', integrated, 'SRF', 'ChIP-seq', and, 'Hi-C', 'data,', we, identified, over, 700, 'TCF-dependent', 'SRF', direct]), verbo([target]), complemento([genes, involved, in, 'signaling,', 'transcription,', and, proliferation])]). relacion([sujeto(['These', also, include, a, significant, number, of, cytoskeletal, gene]), verbo([targets]), complemento([for, the, 'Rho-regulated', 'myocardin-related', transcription, factor, '(', 'MRTF)', 'SRF', cofactor, family])]). relacion([sujeto(['The', 'TCFs']), verbo([act]), complemento([as, general, antagonists, of, 'MRTF-dependent', 'SRF', target, gene, 'expression,', competing, directly, with, the, 'MRTFs', for, access, to, 'SRF'])]). relacion([sujeto(['In', 'February,', 2016, ',', 'WHO']), verbo([released]), complemento([a, report, for, the, development, of, national, action, plans, to, address, the, threat, of, antibiotic, 'resistance,', the, catastrophic, consequences, of, 'inaction,', and, the, need, for, antibiotic, stewardship])]). relacion([sujeto(['In', this, 'Personal', 'View,', we]), verbo([provide]), complemento([examples, of, international, collaborations, to, address, optimal, 'prescribing,', focusing, on, five, countries, that, have, developed, different, approaches, to, antibiotic, 'stewardship-the', 'USA,', 'South', 'Africa,', 'Colombia,', 'Australia,', and, the, 'UK'])]). relacion([sujeto(['We', also, recommend, that, all, 'health-care', providers, who, prescribe, antibiotics, take, ownership, and, understand, the, societal, burden, of, suboptimal, antibiotic, 'use,']), verbo([providing]), complemento([examples, of, how, countries, can, 'learn,', act, 'globally,', and, share, best, antibiotic, stewardship, practices])]). relacion([sujeto(['We', split, the, identified, patients, into, those, with, a, total, preservation, time, of, more, than, 12, h, and, those, with, a, total, preservation, time, of, less, than, 12, h, to]), verbo([act]), complemento([as, the, control, group])]). relacion([sujeto(['Multivariable', survival, analysis, using, 'Cox\'s', model, showed]), verbo([increasing]), complemento([recipient, age, to, be, a, significant, variable, affecting, survival])]). relacion([sujeto(['Extension', of, clinical, lung, preservation, times, might, allow, for, more, transplantations, to, be, done, as, a, result, of, improved, facilitation, and]), verbo([increased]), complemento([flexibility, around, timing, of, lung, transplantation, operations])]). relacion([sujeto(['Both', patients, with, 'non-neuronopathic', 'Gaucher', disease, '(', 'GD)', and, heterozygous, 'GBA', mutation, carrier, are, at]), verbo([increased]), complemento([risk, for, 'Parkinson', disease, '(', 'PD)'])]). relacion([sujeto(['The', risk, for, 'PD', in, these, groups, does, not, linearly]), verbo([increase]), complemento([with, glucosylceramide, '(', 'GC)', accumulation, or, with, acid, 'β-glucocerebrosidase', '(', 'GCase)', activity])]). relacion([sujeto(['This', 'observation,', together, with, other, clinical, systemic, observations, raises, the, possibility, that, 'extra-cellular', 'GC', actually]), verbo([has]), complemento(['beneficial,', 'anti-inflammatory,', properties])]). relacion([sujeto(['Based', on, this, 'hypothesis,', we]), verbo([suggest]), complemento([here, that, the, administration, of, supplementary, oral, 'GC', to, 'GBA', carriers, at, risk, for, 'PD', may, slow, 'inflammatory-driven', secondary, neuronal, death])]). relacion([sujeto(['Such', a, treatment, may]), verbo([act]), complemento([synergistically, in, 'GBA', carriers, once, given, in, combination, with, an, agent, that, prevent, the, primary, pathologic, process, that, leads, to, cell, death])]). relacion([sujeto(['Ambroxol', 'hydrochloride,', a, pharmacological, 'chaperone,', which, reduces, endoplasmic, reticulum, '(', 'ER)', stress]), verbo([induced]), complemento([by, accumulation, of, mutant, misfolded, 'GCase', could, serve, as, such, an, agent])]). relacion([sujeto(['This', determination, for, humanity, to]), verbo([act]), complemento([within, the, strictures, placed, on, itself, by, its, own, nature, was, what, he, called, &, 'quot;lifeboat', ethics])]). relacion([sujeto([&, 'quot;', 'In', order, for, the, citizens, of, the, rich, countries, to, 'survive,', many, in, the, 'Third', 'World', would]), verbo([have]), complemento([to, die])]). relacion([sujeto(['Myocardial', bridging, '(', 'MB)', and, a, long, recurrent, wraparound, left, anterior, descending, artery, '(', 'wrap-LAD)', are, coronary, anatomic, variants, that]), verbo([have]), complemento([been, recently, suggested, to, be, associated, with, takotsubo, syndrome, '(', 'TS)'])]). relacion([sujeto(['Until', 'now,', coronary, artery, tortuosity, '(', 'CAT)']), verbo([has]), complemento([never, been, investigated, in, this, setting])]). relacion([sujeto(['An', anatomic, variant, was]), verbo([found]), complemento([in, 79, patients, with, 'TS', '(', 72, '%', ')', and, in, 48, controls, '(', 44, '%', ')', '(', p, &, 'lt;0'])]). relacion([sujeto(['In', 'conclusion,', 'CAT', and, 'wrap-LAD']), verbo([have]), complemento([higher, prevalence, in, patients, with, 'TS', than, in, matched, controls])]). relacion([sujeto(['These', findings, could, support, the, hypothesis, that, anatomic, variants, might]), verbo([act]), complemento([as, potential, pathogenic, substrates, in, 'TS'])]). relacion([sujeto(['A', facile, and, green, strategy, is]), verbo([reported]), complemento([here, to, synthesize, gold, '(', 'Au),', silver, '(', 'Ag)', and, 'gold-silver', '(', 'Au-Ag)', alloy, nanoparticles, '(', 'NPs)', through, 'bio-reduction', reactions, of, aqueous, corresponding, metal, precursors, mediated, by, extracts, of, aerial, parts, of, 'R'])]). relacion([sujeto(['hypocrateriformis,', which]), verbo([act]), complemento([as, both, reducing, and, stabilizing, 'agents,', under, microwave, irradiation])]). relacion([sujeto(['Moreover,', these, 'NPs', showed]), verbo([enhanced]), complemento(['antimicrobial,', 'antioxidant,', and, anticancer, 'activities,', though, it, is, more, pronounced, for, 'Au-Ag', alloy, 'NPs,', which, is, due, to, the, combining, effect, of, 'phytochemicals,', 'Au', and, 'Ag', metals])]). relacion([sujeto(['The', current, and, potential, benefits, of, defining, standards, for, provision, and, use, of, assistive, technology, for, older, adults, during, disasters]), verbo([has]), complemento([received, limited, recognition, in, emergency, management, planning])]). relacion([sujeto(['Older', adults, with, disabilities, utilize, assistive, technology, to]), verbo([maintain]), complemento([their, independence, and, 'dignity,', and, communities, as, well, as, emergency, services, managers, need, to, become, more, aware, of, the, needs, and, preferences, of, these, older, adults, in, their, planning, processes, and, drills, as, well, as, in, service, delivery, during, actual, events])]). relacion([sujeto([1, ',', 3, -, 'Diphenylisobenzofuran', '(', 'DPBF)']), verbo([has]), complemento([been, developed, as, a, selective, probe, for, the, detection, and, quantitative, determination, of, hydrogen, peroxide, in, samples, containing, different, reactive, nitrogen, and, oxygen, species, '(', 'RNOS)'])]). relacion([sujeto(['Under', the, action, of, these, individuals, 'DPBF']), verbo([has]), complemento([been, rapidly, transformed, to, 1, ',', 2, -, dibenzoylbenzene])]). relacion([sujeto(['In', order, to, check, if, 'DPBF', can]), verbo([act]), complemento([as, a, unique, indicator, of, the, total, amount, of, different, 'RNOS,', as, well, as, oxidative, stress, caused, by, an, overproduction, of, these, 'individuals,', a, series, of, experiments, was, carried, 'out,', in, which, 1, ',', 3, -, diphenylisobenzofuran, reacted, with, peroxynitrite, 'anion,', superoxide, 'anion,', hydrogen, 'peroxide,', hypochlorite, anion, and, anions, commonly, present, under, biological, 'conditions,', namely, nitrite, and, nitrate])]). relacion([sujeto(['This', product]), verbo([has]), complemento([been, identified, with, the, use, of, fluorescence, 'spectroscopy,', 'NMR', 'spectroscopy,', high, performance, liquid, chromatography, coupled, with, mass, 'spectrometry,', infrared, 'spectroscopy,', elemental, analysis, and, cyclic, voltammetry])]). relacion([sujeto(['A', linear, relationship, was]), verbo([found]), complemento([between, a, decrease, in, the, fluorescence, intensity, of, 'DPBF', and, the, concentration, of, hydrogen, peroxide, in, the, range, of, concentrations, of, 0.196, -, 3.941, mM])]). relacion([sujeto(['DPBF']), verbo([responds]), complemento([to, hydrogen, peroxide, in, a, very, specific, way, with, the, limits, of, detection, and, quantitation, of, 88, and, 122.8, 'μM,', respectively])]). relacion([sujeto(['Five', different, types, of, sludge, were, 'tested,', including, raw, sludge, '(', 'Group', 1, :, mixed, primary, and, secondary, 'sludge,', waste]), verbo([activated]), complemento([sludge, and, anaerobic, digested, 'sludge)', and, pretreated, sludge, with, prior, solubilisation, '(', 'Group', 2, :, ultrasonic, or, thermal, pretreated, 'sludge)'])]). relacion([sujeto(['After', 'Fe', '(', 'II)', -, oxone, 'conditioning,', the, concentrations, of, dissolved, organic, 'carbon,', protein, and, polysaccharide, of, soluble, extracellular, polymeric, substances, '(', 'SB', 'EPS)']), verbo([increased]), complemento([for, 'Group', 1, ',', but, decreased, for, 'Group', 2])]). relacion([sujeto(['For', all, types, of, sludge, 'investigated,', the, related, organic, compounds, of, loosely]), verbo([bound]), complemento(['(', 'LB)', and, tightly, bound, '(', 'TB)', 'EPS', decreased, with, 'Fe', '(', 'II)', -, oxone, 'conditioning,', and, increased, sludge, filterability, showed, strong, and, positive, correlation, with, the, removal, of, low, molecular, weight, protein, and, neutrals, in, 'LB', 'EPS'])]). relacion([sujeto(['Fe', '(', 'II)', -, oxone, was, very, effective, in, disintegrating, cell, membrane, and]), verbo([caused]), complemento([potential, cell, 'lysis,', as, indicated, by, increased, percentage, of, damaged, microbial, cells])]). relacion([sujeto(['From', this, 'study,', the, mechanism, of, 'Fe', '(', 'II)', -, oxone, conditioning, was, proposed, and, can, be, divided, into, two, 'steps:', '(', 1, ')', 'Oxidation', step, -, sulfate, radicals, degraded, organic, compounds, in, 'LB', and, 'TB', 'EPS', in, sludge, and, transformed]), verbo([bound]), complemento([water, to, free, water, that, was, trapped, in, 'TB', and, 'LB', 'EPS;', 'It', also, damaged, cells, membrane, and, may, help, to, release, intracellular, water, content])]). relacion([sujeto(['Sludge', flocs, were, broken, into, smaller, 'particles;', '(', 2, ')', 'Coagulation', step, -, 'Fe', '(', 'III),', generated, from, the, oxidation, step, can]), verbo([act]), complemento([as, a, coagulant, to, agglomerate, smaller, particles, into, larger, ones, and, reduce, the, repulsive, electrostatic, interactions])]). relacion([sujeto(['This']), verbo([leads]), complemento([to, the, production, of, dark, pigments, that, are, deposited, onto, connective, 'tissues,', a, condition, named, '\'', 'ochronosis\'', and, whose, mechanisms, are, not, completely, clear])]). relacion([sujeto(['LC/MS', and, in, silico, analyses, were, undertaken, to, identify, possible]), verbo([binding]), complemento([sites, for, 'HGA', '(', or, its, oxidative, 'metabolite,', a, benzoquinone, acetate, or, 'BQA)', in, 'SAA'])]). relacion([sujeto(['We']), verbo([found]), complemento([that, 'HGA', might, act, as, an, amyloid, aggregation, enhancer, in, vitro, for, all, the, tested, proteins, and, peptides, in, a, 'time-', and, 'dose-', dependent, 'fashion,', and, identified, a, small, crevice, at, the, interface, between, two, 'HGD', subunits, as, a, candidate, binding, site, for, 'HGA/BQA'])]). relacion([sujeto(['Our', results]), verbo([provide]), complemento([a, possible, explanation, for, the, clinically, verified, onset, of, amyloidotic, processes, in, 'AKU', and, might, lay, the, basis, to, setup, proper, pharmacological, approaches, to, alkaptonuric, 'ochronosis,', which, are, still, lacking])]). relacion([sujeto(['In', this, 'study,', we]), verbo([found]), complemento([that, 'IOP', can, act, as, a, 'broad-spectrum', antiviral, drug, against, feline, viruses, in, the, in, vitro, experiment])]). relacion([sujeto(['Investigation', of, the, mechanism, of, action, of, the, compound, revealed, that, 'IOP', treatment]), verbo([induces]), complemento([its, inhibitory, actions, directly, on, virus, particles, through, blocking, viral, 'binding/absorpting'])]). relacion([sujeto(['More', 'importantly,', we]), verbo([found]), complemento([that, 'IOP', exhibited, 'broad-spectrum', antiviral, activity, against, the, feline, herpesvirus, 1, ',', feline, influenza, virus, 'H3N2', and, 'H5N6,', feline, panleukopenia, virus, and, feline, infectious, peritonitis, virus, that, can, contribute, to, respiratory, and, gastrointestinal, diseases, in, cats])]). relacion([sujeto(['These', findings]), verbo([suggest]), complemento([that, 'IOP', may, be, a, potential, 'broad-spectrum', antiviral, drug, against, feline, viruses])]). relacion([sujeto(['Human', participants, performed, an, experiment, in, which, they, had, to, generate, a]), verbo([target]), complemento([at, an, expected, time, 'point,', by, pressing, a, button, while, taking, into, account, a, variable, delay, between, the, act, and, the, stimulus, occurrence])]). relacion([sujeto(['Furthermore,', intertrial, phase, coherence, of, frontal, theta, oscillations, was]), verbo([modulated]), complemento([by, error, 'magnitude,', possibly, indexing, the, degree, of, surprise])]). relacion([sujeto(['Finally,', we]), verbo([found]), complemento([that, delta, phase, at, stimulus, onset, was, correlated, with, future, behavioral, adjustments])]). relacion([sujeto(['Together,', our, findings]), verbo([suggest]), complemento([that, low, frequency, oscillations, play, a, key, role, in, monitoring, and, in, updating, temporal, predictions])]). relacion([sujeto(['The', classic, 'drug-design', strategy, based, on, the, &, 'quot;one-molecule-one-target"', paradigm, was]), verbo([found]), complemento([to, be, ineffective, in, the, case, of, multifactorial, diseases, like, 'AD'])]). relacion([sujeto(['A', novel, 'multi-target-directed', ligand, strategy, based, on, the, assumption, that, a, single, compound, consisting, of, two, or, more, distinct, pharmacophores, is, able, to, hit, multiple]), verbo([targets]), complemento([has, been, proposed, as, promising])]). relacion([sujeto(['The', 'drug-like', properties, of, selected, compounds]), verbo([have]), complemento([been, evaluated, from, the, point, of, view, of, 'blood-brain', barrier, penetration, and, cell, proliferation])]). relacion([sujeto(['We']), verbo([have]), complemento([confirmed, the, multipotent, effect, of, novel, series, of, compounds])]). relacion([sujeto(['They']), verbo([inhibited]), complemento([effectively, 'Aβ', peptide, amyloid, fibrillization, and, affected, the, 'BACE1', activity])]). relacion([sujeto(['Moreover,', they]), verbo([have]), complemento(['AChE', inhibitory, potency, but, they, could, not, potentiate, cholinergic, transmission, via, direct, interaction, with, cholinergic, receptors])]). relacion([sujeto(['All', compounds, were]), verbo([reported]), complemento([to, act, as, an, antagonist, of, both, 'M1', muscarinic, and, 'muscle-type', nicotinic, receptors])]). relacion([sujeto(['We']), verbo([have]), complemento([found, that, 7, -, methoxytacrine, -, memantine, heterodimers, are, able, to, hit, multiple, targets, associated, with, 'Alzheimer\'s', disease, and, 'thus,', have, a, potential, clinical, impact, for, slowing, or, blocking, the, neurodegenerative, process, related, to, this, disease])]). relacion([sujeto(['Mousepox', is]), verbo([caused]), complemento([by, the, orthopoxvirus, ectromelia, virus, '(', 'ECTV),', and, is, thought, to, be, transmitted, via, skin, abrasions])]). relacion([sujeto(['However,', in, contrast, to, data, from, an, intranasal, 'model,', 'N1', protein, was, not]), verbo([required]), complemento([for, virus, dissemination])]). relacion([sujeto(['Further,', neither, 'T', cell, nor, cytokine, responses, were]), verbo([enhanced]), complemento([in, the, absence, of, 'N1'])]). relacion([sujeto(['Together', with, the, early, timing, of, reduced, virus, 'titres,', this]), verbo([suggests]), complemento([that, in, a, cutaneous, 'model,', 'N1', exerts, its, function, at, the, level, of, infected, cells, or, in, the, inhibition, of, the, very, earliest, effectors, of, innate, immunity])]). relacion([sujeto(['Genetic', alterations, of, 'IKZF1', encoding, the, lymphoid, transcription, factor, 'IKAROS', are, a, hallmark, of, high, risk, 'B-progenitor', 'ALL', such, as, 'BCR-ABL1', positive, '(', 'Ph+)', and, 'Ph-like', 'ALL,', and, are]), verbo([associated]), complemento([with, poor, 'outcome,', even, in, the, era, of, contemporary, chemotherapy, incorporating, tyrosine, kinase, inhibitors, in, the, treatment, of, 'Ph+', 'ALL'])]). relacion([sujeto(['Recent', experimental, mouse, modeling, of, 'B-progenitor', 'ALL']), verbo([has]), complemento([shown, that, 'IKZF1', alterations, have, multiple, 'effects,', including, arresting, 'differentiating,', skewing, lineage, of, leukemia, from, myeloid, to, 'lymphoid,', and, in, 'Ph+', 'leukemia,', conferring, resistance, to, 'TKI', therapy, without, abrogating, 'ABL1', inhibition])]). relacion([sujeto(['These', effects, are, in, part]), verbo([mediated]), complemento([by, acquisition, of, an, aberrant, hematopoietic, stem, cell, like, program, accompanied, by, induction, of, cell, surface, expression, of, stem, cell, and, adhesion, molecules, that, mediate, extravascular, invasion, and, residence, in, the, 'niche,', and, activation, of, integrin, signaling, pathways])]). relacion([sujeto(['Rexinoids,', a, synthetic, class, of, retinoids, that, specifically]), verbo([bind]), complemento([to, retinoid, &, 'quot;X"', 'receptors,', such, as, bexarotene, potently, reverse, aberrant, adhesion, and, niche, mislocalization, in, 'vivo,', and, induce, differentiation, and, cell, cycle, arrest])]). relacion([sujeto(['Both', agents]), verbo([act]), complemento([synergistically, with, 'TKI', to, prolong, survival, of, 'Ph+', 'ALL', in, mouse, and, human, xenograft, 'model,', with, long, term, remission, induced, by, 'FAK', inhibitors])]). relacion([sujeto(['Thus,', these, findings]), verbo([provide]), complemento([important, new, conceptual, insights, into, the, mechanisms, by, which, 'IKZF1', alterations, result, in, drug, 'resistance,', and, indicate, that, therapeutic, strategies, directed, against, the, pathways, deregulated, by, 'mutation,', rather, than, attempting, to, restore, 'IKZF1', expression, 'directly,', represent, promising, therapeutic, approaches, in, this, disease])]). relacion([sujeto(['The', application, of, 'RCMM-PMRIS', can, help, to, define, the, extent, of, the, brain, involvement, and, therefore, to, assess, the, radiological, mitochondrial, disease, 'severity,', to, monitor, disease, progression, and, consequently, to]), verbo([act]), complemento([as, an, outcome, measure, for, treatment, effects, in, patients, with, mitochondrial, disease])]). relacion([sujeto(['Previous', research]), verbo([has]), complemento([identified, many, active, or, repressive, transcription, factors, '(', 'TFs)', and, core, transcription, components, and, studied, their, functions, in, vitro, and, in, vivo])]). relacion([sujeto(['Nonetheless,', how, individual, 'TFs']), verbo([act]), complemento([in, concert, to, regulate, mRNA, gene, expression, in, a, single, cell, remains, poorly, understood])]). relacion([sujeto(['Research', in, this, area]), verbo([requires]), complemento([developing, novel, techniques, for, 'single-cell', transcription, imaging, and, integrating, imaging, studies, into, understanding, the, molecular, biology, of, transcription])]). relacion([sujeto(['In', the, past, 'decade,', advanced, cell, imaging]), verbo([has]), complemento([enabled, unprecedented, capabilities, to, visualize, individual, 'TF', 'molecules,', to, track, single, transcription, 'sites,', and, to, detect, individual, mRNA, in, fixed, and, living, cells])]). relacion([sujeto(['These', studies]), verbo([have]), complemento([raised, several, novel, insights, on, transcriptional, regulation, such, as, the, &, 'quot;hit-and-run"', model, and, transcription, bursting, that, could, not, be, obtained, by, in, vitro, biochemistry, analysis])]). relacion([sujeto(['Meanwhile,', further, technical, advancements, are, likely]), verbo([required]), complemento([for, visualizing, distinct, kinetic, steps, of, transcription, on, a, 'single-copy', gene, in, vivo])]). relacion([sujeto(['Supernumerary', teats, '(', 'SNT)', are, any, abnormal, teats]), verbo([found]), complemento([on, a, calf, in, addition, to, the, usual, and, functional, 4, teats])]). relacion([sujeto(['The', presence, of, 'SNT']), verbo([has]), complemento([also, been, termed, hyperthelia, since, the, end, of, the, 19, th, century])]). relacion([sujeto(['Supernumerary', teats, can]), verbo([act]), complemento([as, an, incubator, for, 'bacteria,', infecting, the, whole, 'udder,', and, can, interfere, with, the, positioning, of, the, milking, 'machine,', and, 'consequently,', have, economic, relevance])]). relacion([sujeto(['Caudal', teats, are, in, the, 'rear,', ramal, teats, are, attached, to, another, 'teat,', and, intercalary, teats, are]), verbo([found]), complemento([between, 2, regular, teats])]). relacion([sujeto(['Using', alternative, trait, 'coding,', genomic, regions, on, chromosome, 17, and, 20, were, also, identified, as, being]), verbo([involved]), complemento([in, the, development, of, 'SNT', with, their, own, supernumerary, mammary, gland, tissue])]). relacion([sujeto(['The', 'EMPA-REG', 'OUTCOME', and, the, 'LEADER', trials]), verbo([have]), complemento([revealed, a, new, era, in, the, management, of, type, 2, diabetes])]). relacion([sujeto(['These', two, medications]), verbo([act]), complemento([through, different, mechanisms, and, has, consequently, shown, different, patterns, of, cardiovascular, benefit])]). relacion([sujeto(['Based', on, the, different, temporal, pattern, of, achieving, clinical, benefit, one, might, flirt, with, the, idea, that, liraglutide, seems, to]), verbo([provide]), complemento([a, chronic, &, 'quot;protection"', that, better, fits, in, a, longer, metabolic, effect, with, an, impact, in, the, progression, of, 'atherosclerosis,', whilst, empagliflozin, provides, an, acute, effect, compatible, with, an, immediate, hemodynamic, action])]). relacion([sujeto(['After', years, going, from, &, 'quot;bench', to, 'bedside"', in, order, to, discover, the, holy, grail, of, 'cardioprotection,', these, 2, new, studies]), verbo([suggest]), complemento([that, we, may, have, reached, this, state, and, it, is, time, to, go, from, &, 'quot;bed', back, to, bench, 'side"', to, understand, the, mechanisms, of, this, potential, paradigm, shift])]). relacion([sujeto(['EPR', spectroscopy]), verbo([suggests]), complemento([that, the, 'NN', ligands, act, as, bidentate, and, bind, through, both, nitrogen, donor, atoms, in, an, 'axial-equatorial', mode])]). relacion([sujeto(['Most', complexes, showed, no, detectable, interaction, with, plasmid, 'DNA,', except, 2, and, 7, which, depicted, low, ability, to]), verbo([induce]), complemento([single, strand, breaks, in, supercoiled, 'DNA'])]). relacion([sujeto(['Morphology', of, treated, cells, showed]), verbo([nuclear]), complemento([atypia, and, membrane, 'alterations,', more, severe, for, 1])]). relacion([sujeto(['Complexes']), verbo([induce]), complemento([different, cell, death, 'pathways,', predominantly, necrosis, for, 1, and, apoptosis, for, 2])]). relacion([sujeto(['The', purpose, of, this, analysis, 'was:', '(', 1, ')', to, estimate, the, effect, of, the, 'ACA', 'LVH', adjustment, on, qualifying, 'hospitals\'', profitability, 'margins;', and, '(', 2, ')', to, examine, hospital, and, market, characteristics, of, the, hospitals, that, would, be, most, adversely, affected, by, the]), verbo([loss]), complemento([of, the, 'ACA', 'LVH', adjustment])]). relacion([sujeto(['Hospitals', that, would, be, the, most, adversely, affected, by]), verbo([loss]), complemento([of, the, 'ACA', 'LVH', adjustment, were, more, likely, to, be, 'small,', located, in, the, 'South,', and, in, 'high-poverty', markets, with, higher, proportions, of, black, and, uninsured, individuals])]). relacion([sujeto(['Elimination', of, the, 'ACA', 'LVH', adjustment, would]), verbo([have]), complemento([differential, effects, on, subgroups, of, 'hospitals,', and, those, located, in, markets, serving, historically, underserved, populations, would, be, the, most, adversely, affected])]). relacion([sujeto(['Sunlight-driven', dinitrogen, fixation, can]), verbo([lead]), complemento([to, a, novel, concept, for, the, production, of, ammonia, under, mild, conditions])]). relacion([sujeto(['However,', the, efficient, artificial, photosynthesis, of, ammonia, from, ordinary, air, '(', instead, of, high, pure, 'N2', ')']), verbo([has]), complemento([never, been, implemented])]). relacion([sujeto(['Here,', we]), verbo([report]), complemento([for, the, first, time, the, intrinsic, catalytic, activity, of, 'Bi2', 'MoO6', catalyst, for, direct, ammonia, synthesis, under, light, irradiation])]). relacion([sujeto(['The', 'edge-exposed', coordinatively, unsaturated, 'Mo', atoms, in, an, 'Mo-O', coordination, polyhedron, can]), verbo([act]), complemento([as, activation, centers, to, achieve, the, 'chemisorption,', 'activation,', and, photoreduction, of, dinitrogen, efficiently])]). relacion([sujeto(['However,', very, little, is, known, about, the, extrinsic, signals, that]), verbo([act]), complemento([on, planarian, stem, cells, to, modulate, rates, of, neurogenesis])]). relacion([sujeto(['We']), verbo([have]), complemento([identified, two, planarian, homeobox, transcription, 'factors,', 'Smed-nkx2'])]). relacion([sujeto([1, and, 'Smed-arx,', which, are]), verbo([required]), complemento([for, the, maintenance, of, 'cholinergic,', 'GABAergic,', and, octopaminergic, neurons, in, the, planarian, 'CNS'])]). relacion([sujeto(['These', very, same, neurons, also, produce, the, planarian, hedgehog, ligand, '(', 'Smed-hh),', which, appears, to, communicate, with, 'brain-adjacent', stem, cells, to]), verbo([promote]), complemento([normal, levels, of, neurogenesis])]). relacion([sujeto(['Planarian', stem, cells, nearby, the, brain]), verbo([express]), complemento([core, hh, signal, transduction, 'genes,', and, consistent, hh, signaling, levels, are, required, to, maintain, normal, production, of, neural, progenitor, cells, and, new, mature, cholinergic, 'neurons,', revealing, an, important, mitogenic, role, for, the, planarian, hh, signaling, molecule, in, the, adult, 'CNS'])]). relacion([sujeto(['Plant', hormones, are, for, a, long, time, known, to]), verbo([act]), complemento([as, chemical, messengers, in, the, regulation, of, physiological, processes, during, a, 'plant\'s', life, 'cycle,', from, germination, to, senescence])]). relacion([sujeto(['To', study, the, hormonal, regulation, of, physiological, 'processes,', three, main, approaches]), verbo([have]), complemento([been, used, '(', 1, ')', exogenous, application, of, 'hormones,', '(', 2, ')', correlative, studies, through, measurements, of, endogenous, hormone, 'levels,', and, '(', 3, ')', use, of, transgenic, 'and/or', mutant, plants, altered, in, hormone, metabolism, or, signaling])]). relacion([sujeto(['Since', the, discovery, of, 'systemin,', peptides]), verbo([have]), complemento([emerged, as, a, potent, and, diverse, class, of, signaling, molecules, in, plant, systems])]). relacion([sujeto(['Peptides', consist, of, small, amino, acid, 'sequences,', which, often]), verbo([act]), complemento([as, ligands, of, receptor, kinases])]). relacion([sujeto(['Clinical', and, experimental, studies]), verbo([have]), complemento([highlighted, the, significance, of, inflammation, in, coordinating, wound, repair, and, regeneration])]). relacion([sujeto(['However,', it, remains, challenging, to, control, the, inflammatory, response, and, tolerance, at, systemic, levels, without]), verbo([causing]), complemento([toxicity, to, injured, tissues])]). relacion([sujeto(['Mesenchymal', stem, cells, '(', 'MSCs)', possess, potent, immunomodulatory, properties, and, facilitate, tissue, repair, by]), verbo([releasing]), complemento(['exosomes,', which, generate, a, suitable, microenvironment, for, inflammatory, resolution])]). relacion([sujeto(['Exosomes', contain, several, effective, bioactive, molecules, and]), verbo([act]), complemento([as, a, 'cell-cell', communication, vehicle, to, influence, cellular, activities, in, recipient, cells])]). relacion([sujeto(['During', this, 'process,', the, horizontal, transfer, of, exosomal, microRNAs, '(', 'miRNAs)', to, acceptor, 'cells,', where, they]), verbo([regulate]), complemento([target, gene, 'expression,', is, of, particular, interest, for, understanding, the, basic, biology, of, inflammation, 'ablation,', tissue, 'homeostasis,', and, development, of, therapeutic, approaches])]). relacion([sujeto(['These']), verbo([act]), complemento([on, virtually, all, cells, within, the, airway, to, suppress, airway, inflammation, or, prevent, the, recruitment, of, inflammatory, cells, into, the, airway])]). relacion([sujeto(['They', also]), verbo([have]), complemento([profound, effects, on, airway, structural, cells, to, reverse, the, effects, of, disease, on, their, function])]). relacion([sujeto(['Glucorticosteroids']), verbo([act]), complemento([via, specific, 'receptors-the', glucocorticosteroid, receptor, '(', 'GR)-which', are, a, member, of, the, nuclear, receptor, family])]). relacion([sujeto(['As', 'such,', many, of, the, important, actions, of, 'GCs', are, to]), verbo([modulate]), complemento([gene, transcription, through, a, number, of, distinct, and, complementary, mechanisms])]). relacion([sujeto(['GCs', delivered, by, the, inhaled, route, are, very, effective, for, most, patients, and]), verbo([have]), complemento([few, systemic, side, effects])]). relacion([sujeto(['A', number, of, mechanisms, relating, to, inflammation]), verbo([have]), complemento([been, reported, to, be, responsible, for, the, failure, of, these, patients, to, respond, correctly, to, 'GCs', and, these, provide, insight, into, 'GC', actions, within, the, airways])]). relacion([sujeto(['In', these, 'patients,', the, 'side-effect', profile, of, 'GCs']), verbo([prevent]), complemento([continued, use, of, high, doses, and, new, drugs, are, needed, for, these, patients])]). relacion([sujeto(['Targeting', the, defective, pathways]), verbo([associated]), complemento([with, 'GC', function, in, these, patients, may, also, reactivate, 'GC', responsiveness])]). relacion([sujeto(['The', effect, of, practice, facilitation, that]), verbo([provides]), complemento([onsite, quality, improvement, '(', 'QI)', and, electronic, health, record, '(', 'EHR)', coaching, on, chronic, care, outcomes, is, unclear])]). relacion([sujeto(['This', study, evaluates, the, effectiveness, of, such, a, 'program-similar', to, an, agricultural, extension, center, 'model-that']), verbo([provides]), complemento([these, services])]). relacion([sujeto(['The', 'REC', program]), verbo([provides]), complemento([onsite, technical, assistance, to, help, small, primary, care, practices, achieve, meaningful, use, of, certified, 'EHRs'])]). relacion([sujeto(['We', followed, the, first, 50, primary, care, practices, that, utilized, both, 'EHR', and, 'QI', advice]), verbo([targeting]), complemento([diabetes, care])]). relacion([sujeto(['Practice', facilitation, that]), verbo([provided]), complemento(['EHR', and, 'QI', coaching, support, showed, important, improvements, in, diabetes, outcomes, in, practices, that, achieved, meaningful, use, of, their, 'EHR', systems])]). relacion([sujeto(['Besides', degrading, aberrant, mRNAs, that, harbor, a, premature, translation, termination, codon, '(', 'PTC),', 'nonsense-mediated', mRNA, decay, '(', 'NMD)', also]), verbo([targets]), complemento([many, seemingly, &, 'quot;normal"', mRNAs, that, encode, for, 'full-length', proteins])]). relacion([sujeto(['To', identify, a, bona, fide, set, of, such, endogenous, 'NMD']), verbo([targets]), complemento([in, human, 'cells,', we, applied, a, 'meta-analysis', approach, in, which, we, combined, transcriptome, profiling, of, knockdowns, and, rescues, of, the, three, 'NMD', factors, 'UPF1,', 'SMG6', and, 'SMG7'])]). relacion([sujeto(['We']), verbo([provide]), complemento([evidence, that, this, combinatorial, approach, identifies, 'NMD-targeted', transcripts, more, reliably, than, previous, attempts, that, focused, on, inactivation, of, single, 'NMD', factors])]). relacion([sujeto(['Our', data, revealed, that, 'SMG6', and, 'SMG7']), verbo([act]), complemento([on, essentially, the, same, 'transcripts,', indicating, extensive, redundancy, between, the, 'endo-', and, exonucleolytic, decay, routes])]). relacion([sujeto(['Besides', 'mRNAs,', we, also, identified, as, 'NMD']), verbo([targets]), complemento([many, long, 'non-coding', 'RNAs', as, well, as, miRNA, and, snoRNA, host, genes])]). relacion([sujeto(['The', 'NMD']), verbo([target]), complemento([feature, with, the, most, predictive, value, is, an, intron, in, the, 3, '\'', 'UTR,', followed, by, the, presence, of, upstream, open, reading, frames, '(', 'uORFs)', and, long, 3, '\'', 'UTRs'])]). relacion([sujeto(['Furthermore,', the, 3, '\'', 'UTRs', of, 'NMD-targeted', transcripts, tend, to]), verbo([have]), complemento([an, increased, 'GC', content, and, to, be, phylogenetically, less, conserved, when, compared, to, 3, '\'', 'UTRs', of, 'NMD', insensitive, transcripts])]). relacion([sujeto(['Multiciliated', cell, '(', 'MCC)', differentiation]), verbo([involves]), complemento([extensive, organelle, biogenesis, required, to, extend, hundreds, of, motile, cilia])]). relacion([sujeto(['Key', transcriptional, regulators]), verbo([have]), complemento([been, identified, that, drive, gene, expression, required, for, organelle, biogenesis, during, 'MCC', 'differentiation,', which, are, activated, 'by,', and, act, 'downstream,', of, two, 'related,', small, 'coiled-coil', 'proteins,', 'Multicilin', and, 'Gemc1'])]). relacion([sujeto(['Here', we, identify, foxn4, as, a, new, downstream]), verbo([target]), complemento([of, 'Multicilin', required, for, 'MCC', differentiation, in, the, 'Xenopus', skin])]). relacion([sujeto(['When', 'Foxn4', activity, is]), verbo([inhibited]), complemento([in, 'Xenopus', 'embryos,', 'MCCs', show, transient, ciliogenesis, defects, similar, to, those, observed, in, mutants, in, 'Foxj1,', a, known, key, regulator, of, genes, required, for, motile, ciliation])]). relacion([sujeto(['RNAseq', analysis, indicates, that, 'Foxn4', is]), verbo([required]), complemento([to, 'co-activate', some, 'Foxj1', target, genes, strongly, and, many, 'Foxj1', targets, weakly])]). relacion([sujeto(['ChIPseq']), verbo([suggests]), complemento([that, while, 'Foxn4', and, 'Foxj1', frequently, bind, to, different, targets, at, distal, 'enhancers,', they, largely, bind, together, at, 'MCC', gene, promoters])]). relacion([sujeto(['Finally,', in, contrast, to, 'Foxj1,', 'Foxn4', is, not]), verbo([required]), complemento([to, extend, a, single, motile, cilium, by, cells, involved, in, 'left-right', patterning])]). relacion([sujeto(['Together', these, results, indicate, that, 'Foxn4', complements, 'Foxj1', transcriptionally, during, 'MCC', 'differentiation,', thereby, shaping, the, levels, of, gene, expression]), verbo([required]), complemento([for, the, timely, and, complete, biogenesis, of, cilia, in, large, numbers])]). relacion([sujeto(['Allosteric', modulators, of, pentameric, ligand, gated, ion, channels, '(', 'pLGICs)', are, thought, to]), verbo([act]), complemento([on, elements, of, the, pathways, that, couple, agonist, binding, to, channel, gating])]). relacion([sujeto(['Using', α4β2, nicotinic, acetylcholine, receptors, '(', 'nAChRs)', and, the, 'α4β2-selective', positive, modulators, 17, 'β-estradiol', '(', 'βEST)', and, desformylflustrabromine, '(', 'dFBr),', we]), verbo([have]), complemento([identified, pathways, that, link, the, binding, sites, for, these, modulators, to, the, 'Cys', 'loop,', a, region, that, is, critical, for, channel, gating, in, all, pLGICs])]). relacion([sujeto(['Previous', studies]), verbo([have]), complemento([shown, that, the, binding, site, for, potentiating, βEST, is, in, the, 'C-terminal', '(', 'post-M4', 'region)', of, the, α4, subunit])]). relacion([sujeto(['Here,', using, homology, modelling, in, combination, with, mutagenesis, and, 'electrophysiology,', we, identified, the]), verbo([binding]), complemento([site, for, potentiating, dFBr, on, the, 'top-half', of, a, cavity, between, the, third, '(', 'M3)', and, fourth, transmembrane, '(', 'M4)', 'α-helices', of, the, α4, subunit])]). relacion([sujeto(['We']), verbo([found]), complemento([that, the, binding, sites, for, βEST, and, dFBr, communicate, with, the, 'Cys', 'loop,', through, interactions, between, the, last, residue, of, 'post-M4', and, 'F170', of, the, conserved, 'FPF', sequence, of, the, 'Cys', 'loop,', and, that, these, interactions, affect, potentiating, efficacy])]). relacion([sujeto(['Thus,', the, 'Cys', loop]), verbo([acts]), complemento([as, a, key, control, element, in, the, allosteric, transduction, pathway, for, potentiating, βEST, and, dFBr])]). relacion([sujeto(['Overall,', we, propose, that, positive, allosteric, modulators, that]), verbo([bind]), complemento([the, 'M3-M4', cavity, or, 'post-M4', region, increase, the, efficacy, of, channel, gating, through, interactions, with, the, 'Cys', loop])]). relacion([sujeto(['Over', 99, percent, of, tobacco, product, applications, sent, to, the, 'FDA', under, the, new, law]), verbo([have]), complemento([used, this, 'mechanism,', and, loose, application, of, the, 'SE', mechanism, carries, the, risk, of, undoing, the, 'FDA\'s', gatekeeping, power, under, the, law])]). relacion([sujeto(['We', review, the, statutory, and, regulatory, precedent, for, 'SE,', examining, the, 'FSPTCA', itself, as, well, as, regulatory, precedent, from, drug, and, device, regulation, '(', from, which, the, term, &, 'quot;substantial', 'equivalence"', and, much, of, the]), verbo([associated]), complemento([statutory, language, was, 'derived)'])]). relacion([sujeto(['Our', review, of, standards, and, scientific, precedent, demonstrates, that, exacting, scrutiny, under, the, public, health, standard, should, govern, all, 'SE', 'reviews,', and, that, clinical, data, incorporating, social, scientific, evidence, should, be, routinely]), verbo([required]), complemento([for, 'SE', claims, by, tobacco, product, sponsors])]). relacion([sujeto(['Polycomb', chromobox, '(', 'CBX)', proteins]), verbo([participate]), complemento([in, the, polycomb, repressive, complex, '(', 'PRC1)', that, mediates, epigenetic, gene, silencing, and, endows, 'PRC1', with, distinct, oncogenic, or, tumor, suppressor, functions, in, a, 'cell-type-dependent', manner])]). relacion([sujeto(['In', this, 'study,', we]), verbo([report]), complemento([that, inhibition, of, cell, 'migration,', 'invasion,', and, metastasis, in, colorectal, carcinoma, requires, 'CBX4-mediated', repression, of, 'Runx2,', a, key, transcription, factor, that, promotes, colorectal, carcinoma, metastasis])]). relacion([sujeto(['Mechanistically,', 'CBX4']), verbo([maintained]), complemento([recruited, histone, deacetylase, 3, '(', 'HDAC3)', to, the, 'Runx2', 'promoter,', which, maintained, a, deacetylated, histone, 'H3K27', state, to, suppress, 'Runx2', expression])]). relacion([sujeto(['Collectively,', our, data, show, that, 'CBX4', may]), verbo([act]), complemento([as, a, tumor, suppressor, in, colorectal, 'carcinoma,', and, strategies, that, stabilize, the, interaction, of, 'CBX4', with, 'HDAC3', may, benefit, the, colorectal, carcinoma, patients, with, metastases])]). relacion([sujeto(['Inactivation', of, the, cytoplasmic, 'enzyme,', 'Sod1p,', renders, the, cells, sensitive, to, a, variety, of, stresses, while, inactivation, of, the, mitochondrial, 'isoform,', 'Sod2p,', typically]), verbo([has]), complemento([a, weaker, effect])]). relacion([sujeto(['First,', we]), verbo([found]), complemento([that, repression, of, 'SOD2', prevents, 'ethanol-induced', relocalization, of, yeast, hydrogen, 'peroxide-sensing', transcription, factor, 'Yap1p', -, one, of, the, key, 'stress-resistance', proteins])]). relacion([sujeto(['In', agreement, with, 'this,', the, levels, of, 'Trx2p', and, 'Gsh1p,', proteins, encoded, by, 'Yap1-target', 'genes,', were]), verbo([decreased]), complemento([in, the, absence, of, 'Sod2p'])]). relacion([sujeto(['The', analysis, of, the, ethanol, sensitivities, of, the, cells, lacking, 'Sod2p,', 'Yap1p,', or, both, indicated, that, the, two, proteins]), verbo([act]), complemento([in, the, same, pathway])]). relacion([sujeto(['Interestingly,', we]), verbo([found]), complemento([that, 'mitochondria-to-nucleus', signaling, by, 'Rtg-proteins', antagonizes, 'Yap1p', activation])]). relacion([sujeto(['Together,', our, data]), verbo([suggest]), complemento([that, hydrogen, peroxide, produced, by, 'Sod2p', activates, 'Yap1p', and, thus, plays, a, signaling, role, in, ethanol, tolerance])]). relacion([sujeto(['Bakers', yeast, harbor, multiple, systems, that]), verbo([ensure]), complemento([tolerance, to, high, concentrations, of, ethanol])]). relacion([sujeto(['We']), verbo([found]), complemento([that, mitochondrial, superoxide, dismutase, 'Sod2p', and, cytoplasmic, hydrogen, peroxide, sensor, 'Yap1p', act, together, as, a, module, of, 'mitochondria-to-nucleus', signaling, pathway])]). relacion([sujeto(['We', also]), verbo([report]), complemento([a, crosstalk, between, this, pathway, and, the, conventional, retrograde, signaling, cascade, activated, by, dysfunctional, mitochondria])]). relacion([sujeto(['Several', accessory, factors, are, essential, for, assembling, the, two, copper, sites, 'CuA', and, 'CuZ,', and, for]), verbo([maintaining]), complemento([the, activity])]). relacion([sujeto(['The', flavin, transfer, reaction, proceeds, both, in, vivo, and, in, vitro, to, generate, 'post-translationally', modified, 'NosR', with, covalently]), verbo([bound]), complemento(['FMN'])]). relacion([sujeto(['Only', 'FAD', can]), verbo([act]), complemento([as, substrate, and, the, reaction, requires, a, divalent, 'cation,', preferably, 'Mg(2+)', that, was, also, present, in, the, crystal, structure])]). relacion([sujeto(['The', medicinal, plant, generally, known, as, 'monkey\'s', comb, '(', 'Amphilophium', 'crucigerum)']), verbo([has]), complemento([been, popularly, described, for, the, treatment, of, neuropathic, and, inflammatory, 'pain,', specially, seeds, preparations])]). relacion([sujeto(['The', effects, of, 'Crd', and, 'Dcm', was, tested, on, 'capsaicin-induced', 'Ca(2+)', influx, or, the, specific]), verbo([binding]), complemento([of, '[', '(', 3, ')', 'H]-resiniferatoxin'])]). relacion([sujeto(['Moreover,', 'Crd', and, 'Dcm', reduced, 'capsaicin-induced', 'Ca(2+)', influx, and, diminished, the, '[', '(', 3, ')', 'H]-resiniferatoxin', specific]), verbo([binding]), complemento([to, spinal, cord, membranes])]). relacion([sujeto(['Acute', adverse, events, were, not]), verbo([found]), complemento([with, 'Crd', or, 'Dcm', administration])]). relacion([sujeto([crucigerum, and]), verbo([suggest]), complemento([the, presence, of, compounds, that, may, act, as, 'TRPV1', antagonists])]). relacion([sujeto(['Bone', 'marrow-derived', cells, are, thought, to]), verbo([participate]), complemento([and, enhance, the, healing, process, contributing, to, skin, cells, or, releasing, regulatory, cytokines])]). relacion([sujeto(['However,', in, all, cases, we, observed, only, a, partial]), verbo([decrease]), complemento([in, directionality, of, cell, movement, after, inhibition, of, certain, proteins])]). relacion([sujeto(['Additionally,', although, we, noticed, the, accumulation, of, 'EGFR', at, the, cathodal, side, of, 'MSCs,', it, was, not]), verbo([involved]), complemento([in, electrotaxis])]). relacion([sujeto(['In', 'conclusion,', the, physiological, 'DC-EF', may]), verbo([act]), complemento([as, a, factor, positioning, bone, marrow, cells, within, a, wound, bed, and, the, opposite, direction, of, 'MSC', and, macrophage, movement, did, not, result, either, from, utilizing, different, signalling, or, redistribution, of, investigated, cell, surface, receptors])]). relacion([sujeto(['The', heat, treatment, at, 400, °, 'C']), verbo([induced]), complemento([a, reduction, of, binding, sites, '(', e])]). relacion([sujeto(['As', a, 'result,', a, supplement, with, the, thermally, modified, palygorskite, '(', 400, °, 'C)', significantly]), verbo([increased]), complemento(['(', 20, -, 30, '%', ;, 'p<0'])]). relacion([sujeto(['Different', methods, of, obtaining, geochemical, threshold, 'values,', which, differentiate, between, background, and, those, samples, with, unusually, high, element, concentrations, and]), verbo([requiring]), complemento(['attention,', are, presented, and, compared, to, 'Western', 'Australia\'s', '\'', ecological, investigation, 'levels\'', '(', 'EILs)', established, for, 14, 'PTEs'])]). relacion([sujeto(['For', the, 12, remaining, elements, '(', 'As,', 'Ba,', 'Cd,', 'Co,', 'Cr,', 'Cu,', 'Hg,', 'Mo,', 'Ni,', 'Pb,', 'Sn', and, 'Zn)', few, sample, sites]), verbo([require]), complemento([investigation, and, as, most, of, these, are, located, far, from, human, activity, 'centres,', they, potentially, suggest, either, minor, local, contamination, or, mineral, exploration, potential, rather, than, pollution])]). relacion([sujeto(['These', 'carbohydrates,', besides, having, great, structural, 'diversity,']), verbo([act]), complemento([as, potential, receptors, for, pathogenic, and, 'non-pathogenic', microorganisms, influencing, susceptibility, and, resistance, to, infection, and, illness])]). relacion([sujeto(['The', mutual, comparisons, of, the, 'SIRT1', expression, levels, in, all, groups]), verbo([have]), complemento([statistical, significance, except, the, one, between, the, mild, and, moderate, groups])]). relacion([sujeto(['Moreover,', western, blot, results, showed, that, the, 'SIRT1', was]), verbo([decreased]), complemento([and, 'p53/Ac-p53', were, increased, in, the, 'OA', group])]). relacion([sujeto(['The', average, gray, level, of, 'SIRT1']), verbo([increases]), complemento([with, the, improving, grade, of, the, improved, 'Mankin', grading, system, scorers])]). relacion([sujeto(['The', expression, of, 'SIRT1', in, articular, cartilage, is, negatively]), verbo([associated]), complemento([with, severity, of, knee, 'OA,', indicating, that, 'SIRT1', may, act, as, a, monitoring, indicator, for, determining, development, and, progression, of, knee, 'OA'])]). relacion([sujeto(['Recent', data]), verbo([have]), complemento([shown, that, γδ, 'T', cells, can, act, as, mediators, for, immune, defense, against, tumors])]). relacion([sujeto(['Our', previous, study]), verbo([has]), complemento([demonstrated, that, persisting, clonally, expanded, 'TRDV4', 'T', cells, might, be, relatively, beneficial, for, the, outcome, of, patients, with, 'T', cell, acute, lymphoblastic, leukemia, after, hematopoietic, stem, cell, transplantation, '(', 'HSCT)'])]). relacion([sujeto(['The', most, frequently]), verbo([expressed]), complemento(['TRDV', subfamilies, in, the, 'AML', patients, were, 'TRDV8', '(', 86.67, '%', ')', and, 'TRDV2', '(', 83.33, '%', ')', ',', and, the, frequencies, for, 'TRDV1,', 'TRDV3,', 'TRDV4,', and, 'TRDV6', were, significantly, lower, than, those, in, healthy, individuals])]). relacion([sujeto(['While', the, function, of, such, γδ, 'T', cell, clones]), verbo([requires]), complemento([further, 'investigation,', 'TRDV', γδ, 'T', cell, clones, might, be, potential, immune, biomarkers, for, 'AML', outcome])]). relacion([sujeto(['Introduction', of, direct]), verbo([acting]), complemento([antivirals, against, hepatitis, 'C', virus, '(', 'HCV)', has, provided, a, revolutionary, improvement, in, the, treatment, outcome])]). relacion([sujeto(['In', contrast, to, 'HCV,', 'however,', the, strategy, for, developing, new, antiviral, agents, against, hepatitis, 'B', virus, '(', 'HBV),', especially, 'viral-targeting', 'compounds,', is, limited, since, 'HBV']), verbo([requires]), complemento([only, four, viral, genes, for, its, efficient, 'replication/infection'])]). relacion([sujeto(['Here,', we, identify, an, oligomeric, 'flavonoid,', proanthocyanidin, '(', 'PAC)', and, its, 'analogs,', which]), verbo([inhibit]), complemento(['HBV', entry, into, host, cells, by, targeting, the, 'HBV', large, surface, protein, '(', 'LHBs)'])]). relacion([sujeto(['Through', 'cell-based', chemical, 'screening,', 'PAC', was, identified, to]), verbo([inhibit]), complemento(['HBV', infection, with, little, cytotoxic, effect])]). relacion([sujeto(['PAC']), verbo([prevented]), complemento([the, attachment, of, the, preS1, region, in, the, 'LHBs', to, its, cellular, 'receptor,', sodium, taurocholate, cotransporting, polypeptide, '(', 'NTCP)'])]). relacion([sujeto(['PAC', was, shown, to]), verbo([target]), complemento(['HBV', particles, and, impair, their, 'infectivity,', while, it, did, not, affect, the, 'NTCP-mediated', bile, acid, transport, activity])]). relacion([sujeto(['Chemical', biological, techniques, demonstrated, that, 'PAC', directly]), verbo([interacted]), complemento([with, the, region, essential, for, receptor, binding, in, the, preS1, region, in, the, 'LHBs', protein])]). relacion([sujeto(['PAC', and, its, analogs, present, a, new, class, of, 'anti-HBV', agents, that, directly]), verbo([target]), complemento([the, preS1, region, of, the, 'HBV', large, surface, protein])]). relacion([sujeto(['YWHAE', may]), verbo([act]), complemento([as, a, negative, regulator, of, the, cyclin, 'CDC25B,', which, is, a, transcriptional, target, of, 'MYC', oncogene])]). relacion([sujeto(['The', understanding, of, 'YWHAE', role, and, its]), verbo([targets]), complemento([is, important, for, the, better, knowledge, of, gastric, carcinogenesis])]). relacion([sujeto(['In', gastric, cancer, cell, 'lines,', 'YWHAE', was, able, to]), verbo([inhibit]), complemento([the, cell, 'proliferation,', invasion, and, migration, through, the, reduction, of, 'MYC', and, 'CDC25B', expression])]). relacion([sujeto(['Conversely,', 'MYC']), verbo([induced]), complemento([the, cell, 'proliferation,', invasion, and, migration, through, the, induction, of, 'CDC25B', and, the, reduction, of, 'YWHAE'])]). relacion([sujeto(['Most', of, the, tumors, presented, reduced, 'YWHAE', and]), verbo([increased]), complemento(['CDC25B', 'expression,', which, seems, to, be, important, for, tumor, development])]). relacion([sujeto(['Increased', 'MYC', expression, was, a, common]), verbo([finding]), complemento([in, gastric, cancer, and, has, a, role, in, poor, prognosis])]). relacion([sujeto(['Our', gene, signature, also]), verbo([has]), complemento([the, potential, to, predict, patients, in, stage, 'II-III', that, are, likely, to, benefit, from, 'ACT'])]). relacion([sujeto(['Purpose', 'Colorectal', cancer, is, the, third, most, common, cancer, and, the, third]), verbo([leading]), complemento([cause, of, cancer, deaths, in, the, 'United', 'States'])]). relacion([sujeto(['Lack', of, insurance, coverage]), verbo([has]), complemento([been, associated, with, more, advanced, disease, at, 'presentation,', more, emergent, admissions, at, time, of, 'colectomy,', and, lower, survival, relative, to, privately, insured, patients])]). relacion([sujeto(['The', 'Massachusetts', insurance, expansion, was]), verbo([associated]), complemento([with, a, 44, '%', increased, rate, of, resection, '(', rate, ratio, =, 1.44, ;, 95, '%', 'CI,', 1.23, to, 1.68, ;, 'P', &, 'lt;'])]). relacion([sujeto([1, ')', ',', a, 6.21, percentage, point]), verbo([decreased]), complemento([probability, of, emergent, admission, '(', 95, '%', 'CI,', -, 11.88, to, -, 0.54, ;, 'P', =])]). relacion([sujeto([32, ')', ',', and, an, 8.13, percentage, point]), verbo([increased]), complemento([probability, of, an, elective, admission, '(', 95, '%', 'CI,', 1.34, to, 14.91, ;, 'P', =])]). relacion([sujeto(['Conclusion', 'The', 2006, 'Massachusetts', health, care, 'reform,', a, model, for, the, 'Affordable', 'Care', 'Act,', was]), verbo([associated]), complemento([with, increased, rates, of, resection, and, decreased, probability, of, emergent, resection, for, colorectal, cancer])]). relacion([sujeto(['Our', findings]), verbo([suggest]), complemento([that, insurance, expansion, may, help, improve, access, to, care, for, patients, with, colorectal, cancer])]). relacion([sujeto(['The', evolutionary, relationships, within, many, of, these, lineages]), verbo([have]), complemento([been, difficult, to, resolve, with, small, numbers, of, 'loci,', and, we, now, know, that, many, lineages, also, exhibit, substantial, cryptic, diversity])]). relacion([sujeto(['For', the, first, 'time,', 'Co3', '(', 'PO4', ')', 2, is, demonstrated, to]), verbo([act]), complemento([as, a, hydrogen, evolving, catalyst, rather, than, being, used, as, an, oxygen, evolving, photoanode])]). relacion([sujeto(['This']), verbo([enhanced]), complemento([photoactivity, is, mainly, due, to, the, staggered, type, 'II', heterojunction, 'system,', in, which, photoinduced, electrons, from, 3, 'D', flowerlike, 'Co3', '(', 'PO4', ')', 2, transfer, to, the, 'RGO', sheets, and, result, in, decreased, charge, 'recombination,', as, evidenced, by, photoluminescence, spectroscopy])]). relacion([sujeto(['This', study, was, undertaken, to, identify, and, analyse, the, impact, of, individual, waypoints, on, an, 'ED', 'patient\'s', journey, and, identify, which, waypoints]), verbo([act]), complemento([as, bottlenecks, to, a, 'hospital\'s', 4, h, 'ED', disposition, performance])]). relacion([sujeto(['This', study]), verbo([involves]), complemento([retrospective, analysis, and, simulation, employing, 2, years, of, 'ED', administrative, data, from, a, sample, of, two, major, and, two, large, metropolitan, hospitals, in, 'Queensland,', 'Australia'])]). relacion([sujeto(['Higher']), verbo([gains]), complemento([in, 'NEAT', compliance, are, associated, with, improvements, in, departure, delay, rather, than, treatment, delay])]). relacion([sujeto(['Building', resilience, is, a, component, of, 'recovery-oriented', mental, health, 'care,', and, 'yet almost', no, research]), verbo([has]), complemento([been, conducted, into, the, resilience, of, people, who, live, with, schizophrenia, and, who, are, routinely, considered, vulnerable])]). relacion([sujeto(['Resilience', is, invoked, in, the, tension, between, opposing, forces, of, challenge, and, support, and, in, the]), verbo([act]), complemento([of, '\'', 'striving\'', to, take, control, of, schizophrenia])]). relacion([sujeto(['Climate', warming, is]), verbo([causing]), complemento([rapid, loss, of, glaciers, and, snowpack, in, mountainous, regions, worldwide])]). relacion([sujeto(['These', changes, are, predicted, to, negatively, impact, the, habitats, of, many, 'range-restricted', 'species,', particularly, 'endemic,', mountaintop, species, dependent, on, the, unique, thermal, and, hydrologic, conditions]), verbo([found]), complemento([only, in, 'glacier-fed', and, 'snowmelt-driven', alpine, streams])]). relacion([sujeto(['Though', progress]), verbo([has]), complemento([been, 'made,', existing, understanding, of, the, 'status,', 'distribution,', and, ecology, of, alpine, aquatic, 'species,', particularly, in, 'North', 'America,', is, 'lacking,', thereby, hindering, conservation, and, management, programs])]). relacion([sujeto([tumana, occurrence]), verbo([increased]), complemento([with, cold, stream, temperatures, and, close, proximity, to, glaciers, and, permanent, snowfields])]). relacion([sujeto([tumana, declined, with]), verbo([increasing]), complemento([distance, from, stream, source])]). relacion([sujeto(['Climate', 'warming-induced', glacier, and, snow]), verbo([loss]), complemento([clearly, imperils, the, persistence, of, 'L'])]). relacion([sujeto(['When', skin, dysbiosis, occurs, as, a, result, of, skin, 'disorders,', probiotics, can]), verbo([act]), complemento([as, 'modulators,', restoring, microbial, balance])]). relacion([sujeto(['Most', of, them, also]), verbo([prevented]), complemento([biofilm, 'formation,', but, only, 'P'])]). relacion([sujeto(['This', study, demonstrates, that, although, all, tested, probiotics, adhered, to, human, 'keratin,', they, showed, limited, ability, to]), verbo([prevent]), complemento([adhesion, of, some, potential, skin, pathogens])]). relacion([sujeto(['Most', of, the, tested, probiotics, successfully]), verbo([prevented]), complemento([biofilm, 'formation,', suggesting, that, they, may, be, successfully, used, in, the, future, as, a, complement, to, conventional, therapies, in, the, treatment, of, a, range, of, skin, disorders])]). relacion([sujeto(['The', topical, use, probiotics, may, be, a, 'natural,']), verbo([targeted]), complemento([treatment, approach, to, several, skin, disorders, and, a, complement, to, conventional, therapies, which, present, many, undesirable, side, effects])]). relacion([sujeto(['The', generalized, estimating, equation, '(', 'GEE)', approach, was, used, to, longitudinally, model, the, factors]), verbo([associated]), complemento([with, total, healthcare, expenditure])]). relacion([sujeto(['Optimal', asthma, control, was]), verbo([associated]), complemento([with, reduced, healthcare, costs])]). relacion([sujeto(['Crisis', helplines, are, designed, to]), verbo([provide]), complemento(['short-term', support, to, people, in, an, immediate, crisis])]). relacion([sujeto(['In', the, 'survey,', callers]), verbo([reported]), complemento([on, their, 'socio-demographics,', reasons, for, their, current, call, and, number, of, calls, made, in, the, past, month])]). relacion([sujeto(['Twenty-two', per, cent]), verbo([reported]), complemento([calling, 20, times, or, more, in, the, past, month, '(', frequent, 'users),', 51, '%', reported, calling, between, 2, and, 19, times, '(', episodic, 'users)', and, 25, '%', reported, calling, once, '(', 'one-off', 'users)'])]). relacion([sujeto(['Frequent', users]), verbo([reported]), complemento([similar, reasons, for, calling, as, other, users, but, they, were, more, likely, to, call, regularly, to, talk, about, their, feelings, '[', 'OR = 6'])]). relacion([sujeto(['This', pattern, of, service, use, is, at, odds, with, the, current, model, of, care, offered, by, crisis, helplines, which, is, designed, to]), verbo([provide]), complemento(['one-off', support])]). relacion([sujeto(['Over', the, last, 'decade,', the]), verbo([recognized]), complemento([host, range, of, hantaviruses, has, expanded, considerably, with, the, discovery, of, distinct, hantaviruses, in, 'shrews,', moles, and, bats])]). relacion([sujeto(['Unfortunately,', 'in-depth', studies, of, these, viruses]), verbo([have]), complemento([been, limited])]). relacion([sujeto(['Here', we, describe, a, comprehensive, analysis, of, the, spatial, 'distribution,', genetic, diversity, and, evolution, of, 'Nova', 'virus,', a, hantavirus, that]), verbo([has]), complemento([the, 'European', mole, as, its, natural, host])]). relacion([sujeto(['Our', analysis, demonstrated, that, 'Nova', virus]), verbo([has]), complemento([a, high, prevalence, and, widespread, distribution, in, 'Belgium'])]). relacion([sujeto(['We', demonstrated, that, waterways, did, not]), verbo([act]), complemento([as, an, environmental, resistance, factor, slowing, down, 'Nova', virus, diffusion, in, the, mole, population])]). relacion([sujeto(['With', this, 'study,', we]), verbo([provide]), complemento([information, about, the, spatial, diffusion, of, 'Nova', virus, and, contribute, sequence, information, that, can, be, applied, in, further, functional, studies])]). relacion([sujeto(['Histones', and, their, posttranslational, modifications]), verbo([have]), complemento([key, roles, in, chromatin, remodeling, and, gene, transcription])]). relacion([sujeto(['Besides', intranuclear, 'functions,', histones]), verbo([act]), complemento([as, 'damage-associated', molecules, when, they, are, released, into, the, extracellular, space])]). relacion([sujeto(['Administration', of, histones, to, animals]), verbo([leads]), complemento([to, systemic, inflammatory, and, toxic, responses])]). relacion([sujeto(['In', contrast, to, canonical, proteases, '(', 'trypsin,', 'chymotrypsin,', and, proteinase, 'K),', 'IgGs', from, human, immunodeficiency, 'virus-infected', patients, purified, by, affinity, chromatography, on, 'Sepharose', containing, immobilized, histones, specifically]), verbo([recognized]), complemento([and, hydrolyzed, only, histones, but, not, many, other, tested, globular, proteins])]). relacion([sujeto(['Because', histones]), verbo([act]), complemento([as, 'damage-associated', 'molecules,', abzymes, against, 'H1', and, other, histones, can, play, important, role, in, pathogenesis, of, acquired, immune, deficiency, syndrome, and, probably, other, different, diseases])]). relacion([sujeto(['Comparing', the, phenotypes, produced, when, cells, are, treated, with, the, 'Hsp90', inhibitors, 'AUY922', or, 17, -, 'AAG', '(', classical, 'inhibitors)', to, cells, with, 'Hsp90alpha', knocked, down]), verbo([reveals]), complemento([that, the, knockdown, phenotype, is, unique, from, that, produced, by, the, inhibitors])]). relacion([sujeto(['Pull-down', assays, using, classical, inhibitors, verify, that, these, molecules, do, not]), verbo([bind]), complemento([to, 'Hsp90', as, their, primary, target])]). relacion([sujeto(['Classical', inhibitors]), verbo([induce]), complemento([similar, protein, markers, as, other, 'anti-cancer', therapies, 'Cisplatin', and, 'bortezomib,', suggesting, that, 'AUY922', and, 17, -, 'AAG', act, on, targets, other, than, 'Hsp90', and, kill, cells, through, multiple, mechanisms])]). relacion([sujeto(['Comparing', these, classical, inhibitors, to, 'C-terminal', 'Hsp90', modulators]), verbo([reveals]), complemento([that, 'C-terminal', modulators, effectively, bind, to, 'Hsp90,', and, induce, phenotypic, markers, consistent, with, the, 'CRISPR', knockdown, data])]). relacion([sujeto(['Our', findings, challenge, the, current, interpretation, of, 'Hsp90', inhibitors]), verbo([suggest]), complemento([that, a, large, body, of, literature, describing, the, 'Hsp90', phenotype, and, inhibitors, requires, 're-examination'])]). relacion([sujeto(['Heat', shock, proteins, '(', 'HSPs)']), verbo([act]), complemento([as, molecular, chaperones, with, important, regulatory, functions])]). relacion([sujeto(['Epididymal', tissue, homogenates, and, epididymal, fluids, were, analysed, by, tandem, mass, spectrometry, '(', 'MS/MS)', to]), verbo([reveal]), complemento([31, polypeptides, with, enzymatic, 'activity,', including, polypeptides, with, antioxidant, 'properties,', structural, and, cell, signalling, functions])]). relacion([sujeto(['The', concentrations, of, the, analysed, 'polypeptides,']), verbo([expressed]), complemento([in, optical, density, units, '(', 'ODU),', differed, significantly, '(', 'p ≤ '])]). relacion([sujeto(['They', are, major, dietary, vitamin, 'A', precursors, and]), verbo([act]), complemento([as, lipophilic, antioxidants, in, a, variety, of, tissues, and, are, associated, with, important, health, benefits, in, humans, and, animals])]). relacion([sujeto([24, ')', than, those]), verbo([found]), complemento([in, llamas, '(', 2.05, &, 'nbsp;± 0'])]). relacion([sujeto(['In', managed, natural, resource, 'systems,', such, as, fisheries, and, 'rangelands,', there, is, a]), verbo([recognized]), complemento(['trade-off', between, managing, for, 'short-term', benefits, and, managing, for, 'longer-term', resilience])]). relacion([sujeto(['For', 'example,', fire, suppression, in, rangelands, can]), verbo([increase]), complemento([grass, biomass, 'short-term,', but, ultimately, result, in, an, 'undesirable,', 'shrub-dominated', system])]). relacion([sujeto(['Analyses', of, this, phenomenon]), verbo([have]), complemento([focused, largely, on, how, management, actions, influence, 'slow-changing', biophysical, system, attributes, '(', such, as, vegetation, 'composition)'])]). relacion([sujeto(['The', pathology, of, natural, resource, management, was, evident, on, some, 'PLCAs:', an]), verbo([increased]), complemento([focus, on, 'revenue-generation', in, 'decision-making', resulted, in, an, increased, frequency, of, actions, to, stabilize, 'short-term', variation, in, large, mammal, 'populations,', which, led, to, increased, revenues, from, ecotourism, or, hunting])]). relacion([sujeto(['On', many, 'PLCAs,', these, management, actions, corresponded, with, a, reduced, focus, on, ecological, 'monitoring,', and, an]), verbo([increase]), complemento([in, extralimital, species, and, game, overstocking])]). relacion([sujeto(['This', 'study\'s', 'unique,', empirical, investigation, of, 'monitoring-management', relationships, illustrates, that, management, informed, by, 'revenue-monitoring', versus, 'ecological-monitoring', can]), verbo([have]), complemento([opposing, consequences, for, natural, resource, 'productivity,', and, the, likelihood, of, unsustainable, management, practices])]). relacion([sujeto(['Promoting', management, actions, that]), verbo([maintain]), complemento([resilience, in, natural, resource, systems, therefore, requires, cognizance, of, why, managers, act, the, way, they, do, and, how, these, actions, can, gradually, shift, managers, towards, unsustainable, strategies])]). relacion([sujeto(['Fluctuating', asymmetry]), verbo([increased]), complemento([with, mercury, concentrations, in, whole, blood, and, breast, feathers, of, 'Forster\'s', terns, '(', 'Sterna', 'forsteri),', a, species, with, elevated, mercury, concentrations])]). relacion([sujeto(['However,', for, 'American', avocets, '(', 'Recurvirostra', 'americana),', 'black-necked', stilts, '(', 'Himantopus', 'mexicanus),', and, 'Caspian', terns, '(', 'Hydroprogne', 'caspia),', we]), verbo([found]), complemento([no, relationship, between, fluctuating, asymmetry, and, either, whole, blood, or, breast, feather, mercury, 'concentrations,', even, though, these, species, had, moderate, to, elevated, mercury, exposure])]). relacion([sujeto(['Our', results, indicate, that, mercury, contamination, may]), verbo([act]), complemento([as, an, environmental, stressor, during, development, and, feather, 'growth,', and, contribute, to, fluctuating, asymmetry, of, some, species, of, highly, contaminated, waterbirds])]). relacion([sujeto(['In', accordance, with, a, hermeneutic, 'tradition,', the, idea, of, the, caring]), verbo([act]), complemento([is, based, on, the, degree, to, which, the, theory, base, is, hermeneutically, appropriated, by, the, caregiver])]). relacion([sujeto(['The', better, the, 'ethos,', essential, concepts, and, theories, are, 'understood,', the, better, the, caring]), verbo([act]), complemento([can, be, understood])]). relacion([sujeto(['Here', we, review, the, major, crossover, pathways, in, plants, and, some, of, the, known, homeostatic, mechanisms, that]), verbo([act]), complemento([during, meiotic, recombination])]). relacion([sujeto(['Finally,', we]), verbo([provide]), complemento([a, brief, perspective, on, the, relevance, of, these, interconnections, for, natural, selection, and, adaptation, in, plants])]). relacion([sujeto(['Optimising', training, and, performance, through, nutrition, strategies, is, central, to, supporting, elite, 'sportspeople,', much, of, which]), verbo([has]), complemento([focused, on, manipulating, the, relative, intake, of, carbohydrate, and, fat, and, their, contributions, as, fuels, for, energy, provision])]). relacion([sujeto(['Moreover,', ketone, bodies, can]), verbo([act]), complemento([as, signalling, 'metabolites,', with, βHB, acting, as, an, inhibitor, of, histone, 'deacetylases,', an, important, regulator, of, the, adaptive, response, to, exercise, in, skeletal, muscle])]). relacion([sujeto(['Initial']), verbo([reports]), complemento([suggest, this, strategy, alters, the, metabolic, response, to, exercise, and, improves, exercise, 'performance,', while, other, lines, of, evidence, suggest, roles, in, recovery, from, exercise])]). relacion([sujeto(['Results']), verbo([suggest]), complemento([that, the, 'ACA', mandate, increased, the, probability, of, breastfeeding, initiation, by, 2.5, percentage, 'points,', which, translates, into, about, 47, ',', 0, more, infants, for, whom, breastfeeding, was, initiated, in, 2014])]). relacion([sujeto(['We']), verbo([find]), complemento([larger, effects, for, 'black,', less, 'educated,', and, unmarried, mothers])]). relacion([sujeto(['The', 'Affordable', 'Care', 'Act-mandated', coverage, of, lactation, services]), verbo([increased]), complemento([breastfeeding, initiation, among, privately, insured, mothers, relative, to, mothers, covered, by, 'Medicaid'])]). relacion([sujeto(['The', magnitude, of, the, effect, size, varied, with, some, evidence, of, certain, groups, being, more, likely, to]), verbo([increase]), complemento([breastfeeding, rates])]). relacion([sujeto(['Relative', to, the, 'pre-reform', period, and, other, 'states,', in, 'Medicaid', expansion, states, with, adult, dental, 'benefits,', dental, care, use]), verbo([increased]), complemento([between, 2, and, 6, percent, points, in, the, second, half, of, 2014, ',', but, most, of, these, changes, were, not, statistically, significant])]). relacion([sujeto(['Early', evidence]), verbo([suggests]), complemento([that, the, 'Affordable', 'Care', 'Act', may, either, not, be, having, a, substantial, impact, on, dental, care, use, or, it, is, too, early, to, assess, the, impact])]). relacion([sujeto(['SGMA', gives, local, agencies, a, high, degree, of, discretion, in, relation, to, a, new, permitting, 'power,', but, the, discretion, is, a, 'double-edged', 'sword:', agencies]), verbo([gain]), complemento([maximum, flexibility, to, tailor, their, regime, to, local, 'conditions,', yet, the, statute, provides, no, direction, on, appropriate, components, of, a, groundwater, permitting, regime])]). relacion([sujeto(['We', compare, a, selection, of, six, other, 'south-western', permitting, regimes, established, in, legislation, for, areas]), verbo([recognized]), complemento([as, requiring, intensive, management, through, 'permitting:', &, 'quot;special', permitting, 'areas"', '(', 'SPAs)'])]). relacion([sujeto(['We']), verbo([find]), complemento([that, permitting, regimes, in, 'south-western', 'SPAs', share, a, structure, containing, several, almost, universal, 'elements,', although, the, policy, settings, that, apply, to, those, elements, vary, widely])]). relacion([sujeto(['Californian', local, 'agencies,', and, its, 'Department', of, 'Water', 'Resources,', which, is, charged, with]), verbo([providing]), complemento([local, agencies, technical, 'advice,', should, have, regard, to, these, permitting, possibilities])]). relacion([sujeto(['We', designed, this, study, to, investigate, whether, cadmium]), verbo([induces]), complemento(['caspase-independent', apoptosis, and, to, investigate, the, relationship, between, the, 'caspase-dependent', and, 'caspase-independent', apoptotic, pathways])]). relacion([sujeto(['Cadmium', '(', 1.25, -, 2.5, 'μM)']), verbo([induced]), complemento([oxidative, stress, in, rat, proximal, tubular, '(', 'rPT)', 'cells,', as, seen, in, the, reactive, oxygen, species, 'levels;', 'N-acetylcysteine', prevented, this])]). relacion([sujeto(['Cyclosporin', 'A', '(', 'CsA)']), verbo([prevented]), complemento([mitochondrial, permeability, transition, pore, opening, and, 'apoptosis;', there, was, mitochondrial, ultrastructural, 'disruption,', mitochondrial, cytochrome, c, '(', cyt, 'c)', translocation, to, the, 'cytoplasm,', and, subsequent, 'caspase-9', and, 'caspase-3', activation])]). relacion([sujeto(['Z-VAD-FMK']), verbo([prevented]), complemento(['caspase-3', activation, and, apoptosis, and, decreased, 'BNIP-3', '(', 'Bcl-2/adenovirus', 'E1B', 19, -, kDa, interacting, protein, 3, ')', expression, levels, and, 'apoptosis-inducing', 'factor/endonuclease', 'G', '(', 'AIF/Endo', 'G)', translocation])]). relacion([sujeto(['Simultaneously,', cadmium]), verbo([induced]), complemento([prominent, 'BNIP-3', expression, in, the, mitochondria, and, cytoplasmic, 'AIF/Endo', 'G', translocation, to, the, nucleus])]). relacion([sujeto(['BNIP-3', silencing, significantly]), verbo([prevented]), complemento(['AIF', and, 'Endo', 'G', translocation, and, decreased, the, apoptosis, 'rate,', cyt, c, 'release,', and, 'caspase-9', and, 'caspase-3', activation])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, 'BNIP-3', is, involved, in, the, 'caspase-independent', apoptotic, pathway, and, is, located, upstream, of, 'AIF/Endo', 'G;', both, the, 'caspase-dependent', and, 'caspase-independent', pathways, are, involved, in, 'cadmium-induced', rPT, cell, apoptosis, and, act, synergistically])]). relacion([sujeto(['However,', major, river, 'outflows,', such, as, of, the, 'Amazon', or, 'Orinoco,', or, strong, currents, may]), verbo([act]), complemento([as, phylogeographic, barriers, to, ongoing, gene, flow])]). relacion([sujeto(['For', 'example,', the, 'Mona', 'Passage,', located, between, 'Puerto', 'Rico', and, 'Hispaniola,']), verbo([has]), complemento([been, postulated, to, impair, larval, exchange, of, several, species])]). relacion([sujeto(['Experimental', studies, demonstrated, that, saffron, '(', 'Crocus', 'sativus)', given, as, a, dietary, supplement, counteracts, the, effects, of, bright, continuous, light, '(', 'BCL)', exposure, in, the, albino, rat, 'retina,', preserving, both, morphology, and, function, and, probably]), verbo([acting]), complemento([as, a, regulator, of, programmed, cell, death, '[', 1, ']'])]). relacion([sujeto(['The', purpose, of, this, study, was, to, ascertain, whether, the, neuroprotective, effect, of, saffron, on, rat, retina, exposed, to, 'BCL', is]), verbo([associated]), complemento([with, a, modulation, of, the, endocannabinoid, system, '(', 'ECS)'])]). relacion([sujeto(['BCL', exposure]), verbo([led]), complemento([to, enhanced, gene, and, protein, expression, of, retinal, 'CB1', and, 'CB2', without, affecting, the, other, 'ECS', elements])]). relacion([sujeto(['Selective', 'CB1', and, 'CB2', antagonists, reduced, photoreceptor, 'death,', preserved, morphology, and, visual, function, of, 'retina,', and, mitigated, the, outer]), verbo([nuclear]), complemento([layer, '(', 'ONL)', damage, due, to, 'BCL'])]). relacion([sujeto(['Of', 'interest,', 'CB2-dependent', neuroprotection, was, more, pronounced, than, that]), verbo([conferred]), complemento([by, 'CB1'])]). relacion([sujeto(['These', data]), verbo([suggest]), complemento([that, 'BCL', modulates, only, distinct, 'ECS', elements, like, 'CB1', and, 'CB2,', and, that, saffron, and, cannabinoid, receptors, could, share, the, same, mechanism, in, order, to, afford, retinal, protection])]). relacion([sujeto(['Scatter-hoarding', rodents, can]), verbo([act]), complemento([as, both, predators, and, dispersers, for, many, 'large-seeded', plants, because, they, cache, seeds, for, future, 'use,', but, occasionally, forget, them, in, sites, with, high, survival, and, establishment, probabilities])]). relacion([sujeto(['The', most, important, fruit, or, seed, trait, influencing, rodent, foraging, behavior, is, seed, 'size;', rodents, prefer, large, seeds, because, they]), verbo([have]), complemento([higher, nutritional, 'content,', but, this, preference, can, be, counterbalanced, by, the, higher, costs, of, handling, larger, seeds])]). relacion([sujeto(['We']), verbo([found]), complemento([that, the, size, of, fruits, and, seeds, influenced, foraging, behavior, in, the, three, rodent, 'species;', the, probability, of, a, fruit, being, harvested, and, hoarded, was, higher, for, larger, fruits, than, for, smaller, ones])]). relacion([sujeto(['In', 'conclusion,', our, results]), verbo([reveal]), complemento([that, larger, 'M'])]). relacion([sujeto([coquimbensis, fruits]), verbo([have]), complemento([higher, probabilities, of, being, 'harvested,', and, ultimately, of, its, seeds, being, hoarded, and, dispersed, by, 'scatter-hoarding', rodents])]). relacion([sujeto(['As', this, plant]), verbo([has]), complemento([no, other, 'dispersers,', rodents, play, an, important, role, in, its, recruitment, dynamics])]). relacion([sujeto(['Recent', analyses]), verbo([have]), complemento([highlighted, the, importance, of, 'somite-derived', signaling, factors, in, regulating, 'HSC', specification, and, emergence, from, dorsal, aorta, hemogenic, endothelium])]). relacion([sujeto(['We']), verbo([provide]), complemento([evidence, that, the, vitamin, 'A', derivative, retinoic, acid, '(', 'RA)', functions, as, an, essential, regulator, of, zebrafish, 'HSC', formation])]). relacion([sujeto(['Temporal', analyses, indicate, that, 'RA', is]), verbo([required]), complemento([for, 'HSC', gene, expression, prior, to, dorsal, aorta, 'formation,', at, a, time, when, the, predominant, 'RA', synthesis, 'enzyme,', 'aldh1a2,', is, strongly, expressed, within, the, paraxial, mesoderm, and, somites])]). relacion([sujeto(['Consequently,', to, understand, how, 'RA']), verbo([regulates]), complemento(['HSC', gene, 'expression,', we, surveyed, the, expression, of, components, of, these, pathways, in, 'RA-depleted', zebrafish, embryos])]). relacion([sujeto(['Furthermore,', pharmacological, inhibitors, of, 'RA', synthesis, and, 'Cxcr4', signaling]), verbo([act]), complemento([in, concert, to, reduce, 'HSC', formation])]). relacion([sujeto(['Our', analyses, demonstrate, that, 'somite-derived', 'RA', functions, to]), verbo([regulate]), complemento([components, of, the, 'Notch', and, 'Cxcl12', chemokine, signaling, pathways, during, 'HSC', formation])]). relacion([sujeto(['Bicuspid', aortic, valve, patients, can, develop, thoracic, aortic, aneurysms, and, therefore]), verbo([require]), complemento([serial, imaging, to, monitor, aortic, growth])]). relacion([sujeto([126, caregivers, '(', 76, '%', of, 'enrolled)']), verbo([reported]), complemento([&, 'gt;1', inhaled, 'medication;', 52, '%', of, caregivers, accurately, identified, medications])]). relacion([sujeto(['Accurate', identification, of, medications, was]), verbo([associated]), complemento([with, a, higher, mean, 'MED', 'ID', score, '(', 8.6, &, 'nbsp;vs', 7.6, ',', 'P', =, 0.01, ')'])]). relacion([sujeto(['Accuracy', was, most, strongly]), verbo([associated]), complemento([with, 'MED', 'ID', scores, '≥8', points, '(', 88, '%', vs, 60, '%', ',', 'P<0'])]). relacion([sujeto(['Most', studies]), verbo([have]), complemento([looked, for, microevolutionary, performance, 'trade-offs', within, insect, 'species,', but, host, use, could, also, be, constrained, by, macroevolutionary, 'trade-offs', caused, by, epistasis, and, historical, contingency])]). relacion([sujeto(['Across', 1, ',', 604, caterpillar, 'species,', we]), verbo([found]), complemento([both, positive, and, negative, pairwise, correlations, between, use, of, 11, 'host-plant', 'orders,', with, overall, network, patterns, suggesting, that, different, 'host-use', constraints, act, over, 'micro-', and, macroevolutionary, timescales])]). relacion([sujeto(['Moreover,', we, observed, few, negative, correlations, overall, despite, the, wide, taxonomic, and, ecological, diversity, of, the, focal, 'host-plant', 'orders,']), verbo([suggesting]), complemento([that, positive, interactions, between, 'host-use', 'adaptations,', not, 'trade-offs,', dominate, the, 'long-term', evolution, of, host, use, in, 'plant-feeding', insects])]). relacion([sujeto(['However,', many, of, them, hardly]), verbo([act]), complemento([as, a, selective, inhibitor, against, a, specific, isoform])]). relacion([sujeto(['Therefore,']), verbo([finding]), complemento([highly, selective, inhibitors, for, different, isoforms, of, 'CA', is, still, an, ongoing, project])]). relacion([sujeto(['Given', the, 'facts,', we, applied, 'PCM', to, investigate, the, interaction, space, and, structural, properties, that]), verbo([lead]), complemento([to, the, selective, inhibition, of, 'CA', isoforms, by, some, dithiocarbamates])]). relacion([sujeto(['Our', models]), verbo([have]), complemento([provided, interesting, structural, information, that, can, be, considered, to, design, compounds, capable, of, inhibiting, different, isoforms, of, 'CA', in, an, improved, selective, manner])]). relacion([sujeto(['No', known, 'meta-syntheses']), verbo([have]), complemento([been, conducted, to, evaluate, the, qualitative, data, that, exist, on, the, experiences, of, women, being, asked, about, their, abuse])]). relacion([sujeto(['WHAT', 'ARE', 'THE', 'IMPLICATIONS', 'FOR', 'PRACTICE?:', 'Mental', health, nurses, are, strongly, encouraged, to, ask, about, and, document, abuse, in, all, of, their, interviews, and, 'assessments,', as, well, as]), verbo([act]), complemento([as, advocates, and, discuss, reported, abuse, within, their, interdisciplinary, 'teams,', to, provide, 'individualized,', 'trauma-informed', care])]). relacion([sujeto(['The', mental, health, nurse, should, listen, 'attentively,', avoid, 'judgement,', offer, 'reassurance,', make, appropriate, referrals, and]), verbo([provide]), complemento([resources, for, 'women,', including, those, with, both, past, and, current, abuse, histories])]). relacion([sujeto(['Introduction', 'Collections', of, quantitative, data, exist, outlining, the, costs, and, benefits, of, asking, female, research, participants, about, their, abuse, 'experiences;', 'however,', no, known, 'meta-syntheses']), verbo([have]), complemento([been, conducted, to, evaluate, the, qualitative, data, that, exist, on, the, experiences, of, women, being, asked, about, their, abuse])]). relacion([sujeto(['Discussion', 'To', maximize, the, therapeutic, impact, of, discussing, 'abuse,', women, must]), verbo([maintain]), complemento([autonomy, and, feel, they, are, in, a, safe, and, confidential, environment])]). relacion([sujeto(['Within', this, supportive, 'atmosphere,', very, few, women]), verbo([report]), complemento([any, regret, after, discussing, abuse, and, are, able, to, identify, positive, outcomes])]). relacion([sujeto(['Researchers', are, encouraged, to, include, women, in, studies, that]), verbo([involve]), complemento([asking, about, abuse, experiences])]). relacion([sujeto(['The', incredible, pollination, mechanisms, displayed, by, orchid, flowers]), verbo([has]), complemento([inspired, biologists, over, the, centuries])]). relacion([sujeto(['Based', on, the, intriguing, flower, 'structures,', the, relationship, among, orchid, species, and, their, pollinators]), verbo([has]), complemento([been, frequently, regarded, as, very, specialised])]). relacion([sujeto(['Given', that, visits, on, flowers, pollinated, by, 'oil-collecting', bees, are, regularly, 'rare,', and, in, 'Oncidiinae', the, flowers, frequently, attractexclusively, species, that]), verbo([act]), complemento([as, effective, 'pollinators,', the, comparative, reproductive, biology, and, pollinator, specificity, of, two, sympatric, 'Gomesa', '(', 'G'])]). relacion([sujeto(['The', results]), verbo([have]), complemento([show, that, in, the, studied, 'population,', both, 'Gomesa', are, visited, by, several, bee, 'species,', but, these, orchids, present, a, specific, pollination, system])]). relacion([sujeto([&, 'nbsp;varicosa,', 'self-compatibility']), verbo([has]), complemento([been, considered, as, an, important, factor, favouring, reproductive, assurance, in, populations, with, low, visitation, 'frequencies,', despite, occurrence, of, inbreeding, depression])]). relacion([sujeto(['Biting', midges, in, the, genus, 'Culicoides']), verbo([act]), complemento([as, vectors, of, arboviruses, throughout, the, world, and, as, vectors, of, filariasis, in, 'Latin', 'America,', the, 'Caribbean,', and, parts, of, 'Africa'])]). relacion([sujeto(['Understanding', of, the, extent, of, acclimation, of, 'light-saturated', net, photosynthesis, '(', 'An', ')', to, temperature, '(', 'T),', and]), verbo([associated]), complemento([underlying, 'mechanisms,', remains, limited])]). relacion([sujeto(['Across', all, 'species,', 'LMA']), verbo([decreased]), complemento([with, increasing, 'Tgrowth'])]). relacion([sujeto(['Similarly,', 'area-based', rates, of, 'Vcmax', at, a, measurement, 'T', of, 25, °, 'C', '(', 'Vcmax(25)', ')', linearly, declined, with]), verbo([increasing]), complemento(['Tgrowth', ',', linked, to, a, concomitant, decline, in, total, leaf, protein, per, unit, leaf, area, and, 'Rubisco', as, a, percentage, of, leaf, 'N'])]). relacion([sujeto(['The', decline, in, 'Rubisco', constrained, 'Vcmax', and, 'An', for, leaves, developed, at, higher, 'Tgrowth', and, resulted, in, poor, predictions, of, photosynthesis, by, currently, widely, used, models, that, do, not, account, for, 'Tgrowth', -]), verbo([mediated]), complemento([changes, in, 'Rubisco', abundance, that, underpin, the, thermal, acclimation, response, of, photosynthesis, in, 'wet-forest', tree, species])]). relacion([sujeto(['A', new, model, is, proposed, that, accounts, for, the, effect, of, 'Tgrowth', -]), verbo([mediated]), complemento([declines, in, 'Vcmax(25)', on, 'An', ',', complementing, current, photosynthetic, thermal, acclimation, models, that, do, not, account, for, 'T-sensitivity', of, 'Vcmax(25)'])]). relacion([sujeto(['GRASP', 'DCE-MRI,', a, multicoil, compressed, sensing, technique, with, high, spatial, resolution, and, flexible, temporal, 'resolution,']), verbo([has]), complemento(['near-comparable', performance, to, conventional, 'VIBE', imaging, for, breast, lesion, evaluation])]). relacion([sujeto(['Reversion', to, the, '\'', dry, 'seed\'', state, of, 'DNA', methylation, upon, 're-oxygenation', may]), verbo([act]), complemento([to, &, 'quot;reset', the, 'clock"', for, the, rapid, molecular, changes, and, cell, division, that, result, upon, 're-oxygenation'])]). relacion([sujeto(['Our', study, aims, to, test, the, effectiveness, of]), verbo([binding]), complemento([communication, based, interventions, '(', vs, classical, persuasive, communication, based, 'ones)', inciting, 'non-donors', to, act, in, favour, of, blood, donation])]). relacion([sujeto(['Nevertheless,', persuasive, media, campaigns, appear, to]), verbo([have]), complemento([little, effect, on, behaviours])]). relacion([sujeto(['As', an, alternative, to, producing, behavioural, 'changes,', many, recent, studies]), verbo([have]), complemento([shown, the, superiority, of, binding, communication, over, persuasive, communication])]). relacion([sujeto(['Then,', they, were, asked, to]), verbo([report]), complemento([their, intention, to, donate, 'blood,', and, their, intention, to, distribute, leaflets, regarding, blood, donation])]). relacion([sujeto(['Binding', communication, is, a, more, effective, strategy, for]), verbo([increasing]), complemento([intention, towards, blood, donation, compared, with, persuasive, 'communication,', especially, when, combined, with, high, credibility, source])]). relacion([sujeto(['Accordingly', this, study, calls, for, more, consideration, of, knowledge, of, social, psychology, to, design, effective, communication, interventions, and]), verbo([increase]), complemento([the, number, of, donations])]). relacion([sujeto(['In', two, 'studies,', we, investigated, whether, 4, -, to, 7, -, 'year-old', children, evidenced, essentialist, reasoning, about, heart, transplants, by, asking, them, to, predict, whether, trading, hearts, with, an, individual, would]), verbo([cause]), complemento([them, to, take, on, the, 'donor\'s', attributes])]). relacion([sujeto([',', endorsing, the, idea, that, a, recipient, of, a, 'pig\'s', heart, would]), verbo([act]), complemento(['pig-like,', but, denying, that, the, recipient, would, become, a, 'pig)'])]). relacion([sujeto(['This']), verbo([finding]), complemento([runs, counter, to, predictions, from, a, strong, interpretation, of, the, &, 'quot;minimalist"', 'position,', an, alternative, to, essentialism])]). relacion([sujeto(['The', differentiation, of, 'ASD', symptoms, from, those, of, severe, intellectual, disability, presents, diagnostic, 'challenges,', which]), verbo([have]), complemento([led, to, more, refined, methods, in, the, clinical, evaluation, of, 'ASD', in, 'DS'])]). relacion([sujeto(['These', improved, phenotypic, characterization, methods, not, only]), verbo([provide]), complemento([better, diagnosis, of, 'ASD', in, 'DS,', but, may, also, be, useful, in, elucidating, the, etiology, of, the, increased, prevalence, of, 'ASD', in, 'DS'])]). relacion([sujeto(['Because', all, individuals, with, the, classic, presentation, of, 'DS']), verbo([have]), complemento([trisomy, 21, ',', it, is, possible, that, those, with, 'co-occurring', 'DS', and, 'ASD', may, have, additional, genetic, variants, which, can, act, as, modifiers, of, the, 'phenotype,', leading, to, the, development, of, 'ASD'])]). relacion([sujeto(['Keds', were, more, prevalent, in, female, '(', 38.0, '%', ')', than, in, male, '(', 33.2, '%', ')', 'dogs,', and, were, more, frequently]), verbo([found]), complemento([in, animals, younger, than, 1, year, '(', 46.2, '%', ')', and, in, 'long-haired', dogs, '(', 36.6, '%', ')'])]). relacion([sujeto(['Hippoboscidae', may]), verbo([act]), complemento([as, vectors, of, pathogens, and, any, shifts, in, their, geographic, range, may, lead, to, the, spread, of, new, diseases, affecting, animals])]). relacion([sujeto(['The', 'ST18', gene, was, proposed, to]), verbo([act]), complemento([either, as, a, tumor, suppressor, or, as, an, oncogene, in, different, human, 'cancers,', but, direct, evidence, for, its, role, in, tumorigenesis, was, missing, so, far])]). relacion([sujeto(['ST18', mRNA, and, protein, were, detectable, neither, in, the, normal, liver, nor, in, cultured, 'hepatoblasts,', but, were, readily]), verbo([expressed]), complemento([following, subcutaneous, engraftment, and, tumor, growth])]). relacion([sujeto(['ST18', expression, in, liver, cells, was]), verbo([induced]), complemento([by, inflammatory, 'cues,', including, acute, or, chronic, inflammation, in, 'vivo,', as, well, as, 'co-culture', with, macrophages, in, vitro])]). relacion([sujeto(['Induction', of, 'ST18', knockdown, in, 'pre-established', 'tumors,']), verbo([caused]), complemento([rapid, tumor, 'involution,', associated, with, pervasive, morphological, 'changes,', proliferative, arrest, and, apoptosis, in, tumor, 'cells,', as, well, as, depletion, of, 'tumor-associated', 'macrophages,', vascular, ectasia, and, hemorrhage])]). relacion([sujeto(['Reciprocally,', systemic, depletion, of, macrophages, in, recipient, animals, had, very, similar, phenotypic, 'consequences,', impairing, either, tumor, development, or, 'maintenance,', and]), verbo([suppressing]), complemento(['ST18', expression, in, the, hepatoblasts])]). relacion([sujeto(['ST18', expression, in, epithelial, cells, is]), verbo([induced]), complemento([by, 'tumor-associated', 'macrophages,', contributing, to, the, reciprocal, 'feed-forward', loop, between, both, cell, types, in, liver, tumorigenesis])]). relacion([sujeto(['These', metabolites, are, the, 'top-down', signaling, messengers, that, set, signaling, through, signaling, pathways, that, are]), verbo([involved]), complemento([in, energy, economy])]). relacion([sujeto(['I', propose, that, the, polymorphisms, in, central, metabolic, genes, shift, metabolite, concentrations, and, in, that, fashion]), verbo([act]), complemento([as, genetic, modifiers, of, the, 'energy-state', coupling, to, the, transcriptional, networks, that, affect, physiological, 'trade-offs', with, significant, fitness, consequences])]). relacion([sujeto(['Serine-arginine', protein, kinase, 1, '(', 'SRPK1)']), verbo([phosphorylates]), complemento([proteins, involved, in, the, regulation, of, several, mRNA, processing, pathways, including, alternative, splicing])]). relacion([sujeto(['SRPK1']), verbo([has]), complemento([been, recently, reported, to, be, 'over-expressed', in, multiple, cancers, including, 'prostate,', 'breast,', lung, and, glioma])]). relacion([sujeto(['Several', studies]), verbo([have]), complemento([shown, that, inhibition, of, 'SRPK1', has, 'anti-tumoural', effects, and, consequently, 'SRPK1', has, become, a, new, candidate, for, targeted, therapies])]). relacion([sujeto(['Interestingly,', in, terms, of, molecular, 'mechanism,', 'SRPK1', seems, to]), verbo([act]), complemento([heterogeneously, and, has, been, reported, to, affect, several, processes, in, different, 'cancers,', for, example, angiogenesis, in, prostate, and, colon, 'cancer,', apoptosis, in, breast, and, colon, cancer, and, migration, in, breast, cancer])]). relacion([sujeto(['A', recent]), verbo([report]), complemento([adds, to, this, 'puzzle,', showing, that, the, main, effect, of, overexpression, of, 'SRPK1', in, 'non-small-cell', lung, carcinoma, is, to, stimulate, a, stem, 'cell-like', phenotype])]). relacion([sujeto(['Following', the, complete, eradication, of, the, alien, piscivorous, perch, 'Perca', fluviatilis, from, a, potable, 'reservoir,', the, abundance, of, the, endemic, western, minnow, 'Galaxias', 'occidentalis,', which, was, previously, undetectable, prior, to, the, initial, eradication, 'event,']), verbo([increased]), complemento([dramatically])]). relacion([sujeto(['The', study]), verbo([reveals]), complemento([the, potential, of, reservoirs, to, act, as, ecological, refuges, and, has, implications, for, understanding, the, relative, effects, of, alien, fishes, v])]). relacion([sujeto(['The', global, expansion, of, aquaculture]), verbo([has]), complemento([changed, the, structure, of, fish, populations, in, coastal, 'environments,', with, implications, for, disease, dynamics])]). relacion([sujeto(['In', 'Pacific', 'Canada,', farmed, salmon]), verbo([act]), complemento([as, reservoir, hosts, for, parasites, and, 'pathogens,', including, sea, lice, '(', 'Lepeophtheirus', salmonis, and, 'Caligus', 'clemensi)', that, can, transmit, to, migrating, wild, salmon])]). relacion([sujeto(['Assessing', the, impact, of, salmon, farms, on, wild, salmon]), verbo([requires]), complemento([regular, monitoring, of, 'sea-louse', infections, on, both, farmed, and, wild, fish])]). relacion([sujeto(['Since', 2001, ',', we]), verbo([have]), complemento([collected, juvenile, pink, '(', 'Oncorhynchus', 'gorbuscha)', and, chum, '(', 'O'])]). relacion([sujeto(['From', sampled, 'fish,', we, recorded, counts, of, parasitic, 'copepodid-,', 'chalimus-,', and, 'motile-stage']), verbo([sea]), complemento([lice])]). relacion([sujeto(['We']), verbo([report]), complemento([louse, abundances, as, well, as, supplementary, observations, of, fish, 'size,', 'development,', and, health])]). relacion([sujeto(['The', drivers, of, background, tree, mortality, 'rates-the', typical, low, rates, of, tree, mortality]), verbo([found]), complemento([in, forests, in, the, absence, of, acute, stresses, like, 'drought-are', central, to, our, understanding, of, forest, 'dynamics,', the, effects, of, ongoing, environmental, changes, on, 'forests,', and, the, causes, and, consequences, of, geographical, gradients, in, the, nature, and, strength, of, biotic, interactions])]). relacion([sujeto(['We']), verbo([found]), complemento(['that:', '(', 1, ')', 'Biotic', mortality, factors, '(', mostly, insects, and, 'pathogens)', dominated, '(', 58, '%', ')', ',', particularly, in, larger, trees, '(', 86, '%', ')'])]). relacion([sujeto(['(', 3, ')', 'We']), verbo([found]), complemento([little, evidence, of, distinct, groups, of, mortality, factors, that, predictably, occur, together, on, trees])]). relacion([sujeto(['Our', results]), verbo([have]), complemento([at, least, three, sets, of, implications])]). relacion([sujeto(['Second,', the, biotic, agents, of, tree, 'mortality,', instead, of, occurring, in, a, few, predictable, 'combinations,', may, generally]), verbo([act]), complemento([opportunistically, and, with, a, relatively, large, degree, of, independence, from, one, another])]). relacion([sujeto(['Although', spatial, scales, at, which, communities, are, studied, may, affect, the, relative, importance, of, such, assembly, 'processes,', spatial, influences, on, community, assembly]), verbo([have]), complemento([not, been, thoroughly, addressed])]). relacion([sujeto(['Moreover,', we, assumed, that, habitat, heterogeneity, would]), verbo([increase]), complemento([with, 'scale,', and, consequently, alleviate, direct, competitive, exclusion, acting, at, finer, scales])]). relacion([sujeto(['Based', on, phylogenetic, 'structure,', assemblages, showed, an]), verbo([increase]), complemento([in, habitat, filtering, '(', i])]). relacion([sujeto([',']), verbo([increased]), complemento([phylogenetic, 'clustering)', as, we, scaled, up, from, fine, to, intermediate, 'assemblages;', 'however,', we, found, mixed, signals, for, habitat, filtering, and, competitive, exclusion, at, the, broadest, spatial, scale])]). relacion([sujeto(['While', habitat, filtering, was]), verbo([found]), complemento([to, have, an, overall, high, relative, importance, during, 'assembly,', we, also, found, influence, of, competitive, exclusion, processes, based, on, limited, morphological, similarity, among, 'co-occurring', species])]). relacion([sujeto(['Our', results, generally, support, an]), verbo([increased]), complemento([influence, of, habitat, filtering, processes, in, broader, scale, assemblages])]). relacion([sujeto(['Moreover,', we]), verbo([suggest]), complemento([that, habitat, filtering, and, competitive, exclusion, processes, act, simultaneously, during, 'assembly,', although, the, relative, influence, of, each, process, may, be, 'spatial-scale', dependent])]). relacion([sujeto(['However,', the, evolutionary, processes, that, could]), verbo([maintain]), complemento([this, sort, of, life, cycle, are, unclear])]). relacion([sujeto(['Most', previous, models, of, ploidy, evolution]), verbo([have]), complemento([assumed, that, the, fitness, effects, of, new, mutations, are, equal, in, haploids, and, homozygous, 'diploids,', 'however,', this, equivalency, is, not, supported, by, empirical, data])]). relacion([sujeto(['Intrinsic', fitness, differences, between, haploids, and, diploids, can, also, arise, 'directly,', for, example, because, diploids, tend, to]), verbo([have]), complemento([larger, cell, sizes, than, haploids])]). relacion([sujeto(['We']), verbo([find]), complemento([parameter, ranges, where, these, two, selective, forces, act, and, show, that, the, balance, between, them, can, favor, convergence, on, a, 'haploid-diploid', life, 'cycle,', which, is, not, observed, in, the, absence, of, intrinsic, fitness, differences])]). relacion([sujeto(['Individuals', from, disadvantaged, communities, are, among, the, millions, of, uninsured, 'Americans']), verbo([gained]), complemento([insurance, under, the, 'Affordable', 'Care', 'Act'])]). relacion([sujeto(['This', study, linked, the, 'Surveillance,', 'Epidemiology,', and, 'End', 'Results', registries, to, 'US', 'Census', data, to, study, patients, diagnosed, with, the, 4]), verbo([leading]), complemento([causes, of, cancer, deaths, between, 2007, and, 2011])]). relacion([sujeto(['A', 'pin-peptide', 'enzyme-linked', immunosorbent, assay, with, synthesized, icosa, peptides, showed, that, 404, -, 117, monoclonal, antibody]), verbo([bound]), complemento([to, peptides, #, 11, -, 13, with, cry, j2, amino, acid, sequence, of, 101, 'F-L140'])]). relacion([sujeto(['When', 'K119', '(', 'Asn)', was, substituted, with, 'alanine,', 404, -, 117, monoclonal, antibody, did, not]), verbo([bind]), complemento([to, the, alanine, substituted, peptide])]). relacion([sujeto(['We', concluded, that, the, 118, 'FKVD121', sequence, might]), verbo([have]), complemento([a, very, important, role, in, early, recognition, by, 'Cry', 'j2-specific', 'B', 'cells,', which, could, act, as, antigen, presenting, cells])]). relacion([sujeto(['The', past, decade]), verbo([has]), complemento([witnessed, a, rapid, increase, in, the, use, of, 'Social', 'Networking', 'Sites', '(', 'SNSs)', in, health, communication, campaigns, seeking, to, achieve, an, ambitious, range, of, 'health-related', impacts])]). relacion([sujeto(['This', article]), verbo([provides]), complemento([a, review, of, 40, studies, and, research, 'protocols,', with, a, focus, on, two, key, factors, that, differentiate, 'SNSs', from, more, traditional, health, communication, approaches, of, the, past])]). relacion([sujeto(['The', second, is, the, potential, dualism, between, message, and, message, 'impact,', in, which, the]), verbo([act]), complemento([of, forwarding, and, modifying, messages, by, 'receiver-sources', itself, becomes, a, measure, of, message, impact])]). relacion([sujeto(['Each', of, these, dualisms]), verbo([has]), complemento([implications, for, the, design, and, evaluation, of, contemporary, health, communication, campaigns])]). relacion([sujeto(['We', show, that, the, global, 'rheology,', as, well, as, the, amplitude, and, correlation, time, of, the, 'fluctuations,', are, consistent, with, a, 'mean-field,', 'Landau-like', 'description,', where, the, strain, rate, and, the, stress]), verbo([act]), complemento([as, conjugated, variables])]). relacion([sujeto(['The', vast, majority, of, chloroplast, transformation, experiments, conducted, thus, far]), verbo([have]), complemento([relied, on, a, single, selectable, marker, 'gene,', the, spectinomycin, resistance, gene, aadA])]). relacion([sujeto(['Although', a, few, alternative, markers]), verbo([have]), complemento([been, 'reported,', the, aadA, has, remained, unrivalled, in, efficiency, and, 'is,', 'therefore,', nearly, exclusively, used])]). relacion([sujeto(['The', development, of, new, marker, genes, for, plastid, transformation, is, of, crucial, importance, to, all, efforts, towards, extending, the, species, range, of, the, technology, as, well, as, to, those, applications, in, basic, 'research,', biotechnology, and, synthetic, biology, that]), verbo([involve]), complemento([the, multistep, engineering, of, plastid, genomes])]). relacion([sujeto(['Here,', we]), verbo([have]), complemento([tested, a, bifunctional, resistance, gene, for, its, suitability, as, a, selectable, marker, for, chloroplast, transformation])]). relacion([sujeto(['The', bacterial, enzyme, aminoglycoside, 'acetyltransferase(6\')-Ie/aminoglycoside', 'phosphotransferase(2″)-Ia', possesses, an, 'N-terminal', acetyltransferase, domain, and, a, 'C-terminal', phosphotransferase, domain, that, can]), verbo([act]), complemento([synergistically, and, detoxify, aminoglycoside, antibiotics, highly, efficiently])]). relacion([sujeto(['We']), verbo([report]), complemento(['that,', in, combination, with, selection, for, resistance, to, the, aminoglycoside, 'tobramycin,', the, 'aac(6\')-Ie/aph(2″)-Ia', gene, represents, an, efficient, marker, for, plastid, transformation, in, that, it, produces, similar, numbers, of, transplastomic, lines, as, the, spectinomycin, resistance, gene, aadA])]). relacion([sujeto(['The', toxins, were, named, actin, 'cross-linking', domains, '(', 'ACD),', since, the, first, and, most, of, the, subsequently, discovered, 'ACDs', were]), verbo([found]), complemento([as, effector, domains, in, larger, 'MARTX', and, 'VgrG', toxins])]). relacion([sujeto(['Among']), verbo([recognized]), complemento([human, 'pathogens,', 'ACD', is, produced, by, 'Vibrio', 'cholerae,', 'Vibrio', 'vulnificus,', and, 'Aeromonas', hydrophila])]). relacion([sujeto(['Provided', sufficient, doses, of, toxin, are, 'delivered,', most, or, all, actin, can, be, promptly, 'cross-linked', into, 'non-functional', 'oligomers,']), verbo([leading]), complemento([to, cell, 'rounding,', detachment, from, the, substrate, 'and,', in, many, 'cases,', cell, death])]). relacion([sujeto(['According', to, this, 'finding,', low, doses, of, the, 'ACD-produced', actin, oligomers, can, actively, disrupt, the, actin, cytoskeleton, by, potently]), verbo([inhibiting]), complemento([essential, actin, assembly, 'proteins,', formins])]). relacion([sujeto(['The', first, layer, of, toxicity, is, direct, '(', as, actin, is, the, immediate, and, the, only, 'target),', passive, '(', since, 'ACD-cross-linked', actin, oligomers, are, toxic, only, because, they, are, 'non-functional),', and, less, potent, '(', as, bulk, quantities, of, one, of, the, most, abundant, cytoplasmic, 'proteins,', 'actin,']), verbo([have]), complemento([to, be, 'modified)'])]). relacion([sujeto(['The', second, mechanism, is, indirect, '(', as, major, 'targets,', 'formins,', are, not, affected, by, 'ACD', 'directly),', active, '(', because, actin, oligomers]), verbo([act]), complemento([as, &, 'quot;secondary"', 'toxins),', and, highly, potent, '[', as, it, affects, scarce, and, essential, 'actin-binding', proteins, '(', 'ABPs)]'])]). relacion([sujeto(['Nest', sanitation]), verbo([has]), complemento([been, posited, as, a, 'pre-adaptation', for, egg, ejection, by, hosts, of, avian, brood, parasites])]). relacion([sujeto(['In', this, 'study,', 'I', added, either, a, piece, of, flagging, tape, or, a, pine, cone, bract, scale, along, with, an, artificial, cowbird, egg, to, nests, of, the, 'red-winged', blackbird, '(', 'Agelaius', 'phoeniceus)', to, determine, whether, the]), verbo([act]), complemento([of, nest, sanitation, would, elicit, egg, ejection])]). relacion([sujeto(['While', nest, cleaning, and, egg, ejection, are, similar, 'mechanically,', they, differ, cognitively, and, egg, ejection, is, not, elicited, in, 'red-winged', blackbirds, during, the]), verbo([act]), complemento([of, removing, debris, from, their, nests])]). relacion([sujeto(['Although', the, model, is, simple, and, 'generic,', we, attempt, to, map, its, 'energy,', length, and, time, scales, onto, a, specific, experimental, 'system,', namely, a, bead, that, is, weakly]), verbo([bound]), complemento([to, a, cell, and, then, removed, by, an, optical, tweezer])]). relacion([sujeto(['β-Haematin', inhibition, assays]), verbo([suggest]), complemento([that, the, compounds, may, in, part, act, via, the, inhibition, of, haemozoin, 'formation,', while, microsomal, metabolic, stability, studies, reveal, that, the, 'ferrocenyl-containing', quinolines, are, rapidly, metabolised, in, liver, microsomes])]). relacion([sujeto(['These', filaments, can, be]), verbo([recruited]), complemento([to, negatively, charged, membrane, surfaces])]). relacion([sujeto(['When']), verbo([associated]), complemento([with, membranes, septin, filaments, can, act, as, diffusion, 'barriers,', which, confine, subdomains, of, distinct, biological, functions])]). relacion([sujeto(['In', 'addition,', they, serve, scaffolding, roles, by]), verbo([recruiting]), complemento([cytosolic, proteins, and, other, cytoskeletal, elements])]). relacion([sujeto(['Septins']), verbo([have]), complemento([been, implicated, in, a, large, variety, of, 'membrane-dependent', 'processes,', including, 'cytokinesis,', 'signaling,', cell, 'migration,', and, membrane, 'traffic,', and, several, family, members, have, been, implicated, in, disease])]). relacion([sujeto(['The', septins, are, a]), verbo([conserved]), complemento([family, of, 'GTP-binding', proteins, present, in, all, eukaryotic, cells, except, plants])]). relacion([sujeto(['The', septins, are, regulators, of, spatial, compartmentalization, in, yeast, and]), verbo([act]), complemento([as, key, players, in, cytokinesis])]). relacion([sujeto(['Humans']), verbo([act]), complemento([as, an, intermediate, host, for, 'Toxocara', canis, and, 'Toxocara', cati])]). relacion([sujeto(['Current', cooking, method]), verbo([requires]), complemento([the, internal, temperature, of, beef, patties, to, reach, 71, °, 'C'])]). relacion([sujeto([coli, 'strains,', sufficient, 'estimations,', and, explanations, are, necessary, on, mechanisms, of, heat, resistance, of]), verbo([target]), complemento([strains])]). relacion([sujeto(['Heat']), verbo([induces]), complemento([alterations, of, 'E'])]). relacion([sujeto([coli]), verbo([act]), complemento([against, these, 'alterations,', mainly, through, gene, regulations, of, heat, response, including, 'EvgA,', heat, shock, 'proteins,', 'σ(E)', and, 'σ(S),', to, 're-fold', of, misfolded, 'proteins,', and, achieve, antagonism, to, heat, stress])]). relacion([sujeto(['Heat', resistance, can, also, be]), verbo([increased]), complemento([by, expression, of, key, proteins, of, membrane, and, stabilization, of, membrane, fluidity])]). relacion([sujeto(['This', review, aims, to]), verbo([provide]), complemento([an, overview, of, current, knowledge, on, heat, resistance, of, 'E'])]). relacion([sujeto(['Epilepsy', may]), verbo([act]), complemento([on, sensory, systems, by, producing, sensory, seizure, 'symptoms,', by, altering, sensory, 'performance,', and, by, epilepsy, treatment, causing, sensory, side, effects])]). relacion([sujeto(['Sensory', system, activity, may]), verbo([have]), complemento([an, important, role, in, both, generation, and, inhibition, of, seizures])]). relacion([sujeto(['Approaching', the, convicted, patient, is, a, topical, issue, in, terms, of, alignment, with, 'EU', provisions, and, 'recommendations,', more, so, in, the, context, of, year, by, year]), verbo([increase]), complemento([in, the, number, of, convicts, and, 'consequently,', prison, patients])]). relacion([sujeto(['The', prison, patient, exhibits]), verbo([increased]), complemento([vulnerability, in, regard, to, the, rest, of, the, convicts, due, to, 'his/her', medical, status, overlapping, personality, changes, 'induced,', while, coping, with, a, new, environment])]). relacion([sujeto(['This', represents, a, challenge, for, the, physicians]), verbo([involved]), complemento([in, the, expertise, 'process,', which, must, act, objectively, within, the, limits, and, by, the, principles, of, professional, 'ethics,', while, confronting, a, patient, influenced, by, the, prison, environment])]). relacion([sujeto(['Convicts', present, pathologies, documented, in, medical, 'records,', but, accuse, new, symptoms, that, could]), verbo([suggest]), complemento([a, new, pathological, condition])]). relacion([sujeto(['Hormones', and, hypothalamic, neuropeptides, '(', that]), verbo([act]), complemento([as, neurotrasmitters, and, neuromodulators, in, the, central, nervous, 'system)', play, a, role, in, the, regulation, of, respiration, and, in, bronchopulmonary, morphology])]). relacion([sujeto(['The', respiratory, abnormalities, in, hyperthyroidism, as, a, result, of, the, hypermetabolic, action, of, thyroid, hormones, are, 'hyperventilation,', myopathy, and, cardiovascular, 'involvement;', recent, studies]), verbo([have]), complemento([reported, pulmonary, arterial, hypertension, in, 'Graves\'', 'disease,', as, a, result, of, the, association, of, several, mechanisms])]). relacion([sujeto(['Thyroid', hypertrophy, can]), verbo([induce]), complemento([through, compression, of, the, upper, airways, 'dyspnea,', 'stridor,', wheezing, and, cough])]). relacion([sujeto(['Respiratory', changes, in, 'parathyroid,', adrenal, and, reproductive, system, diseases]), verbo([have]), complemento([been, described])]). relacion([sujeto(['They', are, frequently, 'severe,']), verbo([causing]), complemento([an, unfavorable, evolution, of, the, associated, endocrine, and, respiratory, disease])]). relacion([sujeto(['We']), verbo([report]), complemento([on, a, quality, improvement, project, to, implement, and, refine, such, a, protocol])]). relacion([sujeto(['Across', the, three, 'cohorts,', use, of, 'PCC']), verbo([increased]), complemento([over, time, from, 15, '%', to, 100, '%', of, eligible, patients, '(', 'p<0'])]). relacion([sujeto(['The', introduction, '(', and, 'revisions)', of, an, anticoagulation, reversal, strategy, for, 'WRICH']), verbo([has]), complemento([led, to, increased, 'PCC', use, and, reduced, times, to, both, diagnosis, and, treatment])]). relacion([sujeto(['Further', work, is]), verbo([required]), complemento([to, improve, 'door-needle', times, and, monitoring])]). relacion([sujeto(['Epigenetics', refers, to, the, study, of, heritable, changes, in, gene, expression, not]), verbo([involving]), complemento([changes, in, 'DNA', sequence, and, is, presently, an, active, area, of, research, in, biology, and, medicine])]). relacion([sujeto(['There', is]), verbo([increasing]), complemento([evidence, that, epigenetics, is, involved, in, the, pathogenesis, of, psychiatric, disorders])]). relacion([sujeto(['Several', studies, conducted, to, date]), verbo([have]), complemento([suggested, that, psychosocial, factors, act, by, modifying, epigenetic, mechanisms, of, gene, expression, in, the, brain, in, the, pathogenesis, of, psychiatric, disorders])]). relacion([sujeto(['Such', studies]), verbo([have]), complemento([been, conducted, both, on, brain, tissues, and, also, using, peripheral, tissues, as, substitutes, for, brain, tissues])]). relacion([sujeto(['Rapid', progress, in, nanophotonics, is, driven, by, the, ability, of, optically, resonant, nanostructures, to]), verbo([enhance]), complemento(['near-field', effects, controlling, 'far-field', scattering, through, intermodal, interference])]). relacion([sujeto(['A', majority, of, such, effects, are, usually]), verbo([associated]), complemento([with, plasmonic, nanostructures])]). relacion([sujeto(['Recently,', a, new, branch, of, nanophotonics]), verbo([has]), complemento([emerged, that, seeks, to, manipulate, the, 'strong,', optically, induced, electric, and, magnetic, 'Mie', resonances, in, dielectric, nanoparticles, with, high, refractive, index])]). relacion([sujeto(['In', the, design, of, optical, nanoantennas, and, 'metasurfaces,', dielectric, nanoparticles, offer, the, opportunity, for, reducing, dissipative]), verbo([losses]), complemento([and, achieving, large, resonant, enhancement, of, both, electric, and, magnetic, fields])]). relacion([sujeto(['We', review, this, rapidly, developing, field, and, demonstrate, that, the, magnetic, response, of, dielectric, nanostructures, can]), verbo([lead]), complemento([to, novel, physical, effects, and, applications])]). relacion([sujeto(['Uncertainty', surrounding, the, burst, 'sources,', and, their, propagation, through, intervening, 'plasma,']), verbo([has]), complemento([limited, their, use, as, cosmological, probes])]). relacion([sujeto(['We']), verbo([report]), complemento([on, a, mildly, dispersed, '(', dispersion, measure, 266.5, ±, 0.1, pc, 'cm(-3)),', exceptionally, intense, '(', 120, ±, 30, 'Jy),', linearly, 'polarized,', scintillating, burst, '(', 'FRB', 150807, ')', that, we, directly, localize, to, 9, 'arcmin(2)', 'Based', on, a, low, 'Faraday', rotation, '(', 12.0, ±, 0.7, rad, 'm(-2)),', we, infer, negligible, magnetization, in, the, 'circum-burst', plasma, and, constrain, the, net, magnetization, of, the, cosmic, web, along, this, sightline, to, &, 'lt;21', 'nG,', parallel, to, the, 'line-of-sight'])]). relacion([sujeto(['The', burst, scintillation]), verbo([suggests]), complemento([weak, turbulence, in, the, ionized, intergalactic, medium])]). relacion([sujeto(['For', outpatient, costs, 'pmpm,', higher, utilization, rather, than, unit, cost, per, visit, drove]), verbo([increased]), complemento([costs])]). relacion([sujeto(['To', test, whether, genetically]), verbo([decreased]), complemento([vitamin, 'D', levels, are, associated, with, 'Alzheimer', disease, '(', 'AD)', using, mendelian, randomization, '(', 'MR),', a, method, that, minimizes, bias, due, to, confounding, or, reverse, causation])]). relacion([sujeto(['We', selected, single, nucleotide, polymorphisms, '(', 'SNPs)', that, are, strongly]), verbo([associated]), complemento([with, 25, -, hydroxyvitamin, 'D', '(', 25, 'OHD)', levels, '(', p, &, 'lt;', 5, ×, 10, '(', -, 8, ')', ')', from, the, 'Study', of, 'Underlying', 'Genetic', 'Determinants', of, 'Vitamin', 'D', and, 'Highly', 'Related', 'Traits', '(', 'SUNLIGHT)', 'Consortium', '(', 'N', =, 33, ',', 996, ')', to, act, as, instrumental, variables, for, the, 'MR', study])]). relacion([sujeto(['To', produce, 'MR', 'estimates,', we, weighted, the, effect, of, each, 'SNP', on, 'AD', by, its, effect, on, 25, 'OHD', and, 'meta-analyzed', these, estimates, using, a, 'fixed-effects', model, to]), verbo([provide]), complemento([a, summary, effect, estimate])]). relacion([sujeto(['MR', analyses, demonstrated, that, a, 1, -, 'SD']), verbo([decrease]), complemento([in, natural, 'log-transformed', 25, 'OHD', increased, 'AD', risk, by, 25, '%', '(', odds, ratio, 1.25, ',', 95, '%', confidence, interval, 1.03, -, 1.51, ',', p, =, 0.021, ')'])]). relacion([sujeto(['Our', results]), verbo([provide]), complemento([evidence, supporting, 25, 'OHD', as, a, causal, risk, factor, for, 'AD'])]). relacion([sujeto(['These', findings]), verbo([provide]), complemento([further, rationale, to, understand, the, effect, of, vitamin, 'D', supplementation, on, cognition, and, 'AD', risk, in, randomized, controlled, trials])]). relacion([sujeto(['Research', in, youth, is, 'sparse,', but, the, available, evidence, supports, that, paraphilic, disorders]), verbo([respond]), complemento([favourably, to, psychological, and, pharmacological, treatments])]). relacion([sujeto(['The', detection, of, paraphilic, disorders, in, adolescents, and, youth, presents, a, window, of, 'opportunity,', where, treatment, may, be]), verbo([provided]), complemento([before, deviant, behaviour, 'occurs,', potentially, reducing, the, future, incidence, of, sexual, abuse])]). relacion([sujeto(['Photons', with, a, twisted, phase, front, carry, a, quantized, amount, of, orbital, angular, momentum, '(', 'OAM)', and]), verbo([have]), complemento([become, important, in, various, fields, of, 'optics,', such, as, quantum, and, classical, information, science, or, optical, tweezers])]). relacion([sujeto(['To', our, 'knowledge,', this, corresponds, to, entanglement, with, the, largest, quantum, number, that]), verbo([has]), complemento([been, demonstrated, in, an, experiment])]). relacion([sujeto(['The', results, may, also, open, novel, ways, to, couple, single, photons, to, massive, 'objects,']), verbo([enhance]), complemento([angular, 'resolution,', and, highlight, 'OAM', as, a, promising, way, to, increase, the, information, capacity, of, a, single, photon])]). relacion([sujeto(['Every', close, relationship]), verbo([has]), complemento([a, 'history,', but, how, people, manage, their, relational, past, varies, and, can, have, important, implications, in, the, present])]). relacion([sujeto(['We']), verbo([found]), complemento([support, for, our, hypothesis, that, when, negative, memories, felt, subjectively, closer, relative, to, positive, 'memories,', people, were, more, likely, to, kitchen, think, '(', 'Studies', 1, -, 3, ')'])]). relacion([sujeto(['The', 'SnRK1', '(', 'SNF1-related', kinase, 1, ')', kinases, are, the, plant, cellular, fuel, 'gauges,']), verbo([activated]), complemento([in, response, to, 'energy-depleting', stress, conditions, to, maintain, energy, homeostasis, while, also, gatekeeping, important, developmental, transitions, for, optimal, growth, and, survival])]). relacion([sujeto(['Although', the, overall, configuration, of, the, kinase, complexes, is, well, 'conserved,', 'plant-specific', structural, modifications, '(', including, a, unique, hybrid, βγ, 'subunit)', and]), verbo([associated]), complemento([differences, in, regulation, reflect, evolutionary, divergence, in, response, to, fundamentally, different, lifestyles])]). relacion([sujeto(['While', 'AMP', is, the, key, metabolic, signal]), verbo([activating]), complemento(['AMPK', in, 'animals,', the, plant, kinases, appear, to, be, allosterically, inhibited, by, 'sugar-phosphates'])]). relacion([sujeto(['The', 'SnRK1', kinases]), verbo([act]), complemento([by, direct, phosphorylation, of, key, metabolic, enzymes, and, regulatory, 'proteins,', extensive, transcriptional, regulation, '(', e])]). relacion([sujeto([through, bZIP, transcription, 'factors),', and, 'down-regulation', of, 'TOR', '(']), verbo([target]), complemento([of, 'rapamycin)', kinase, signaling])]). relacion([sujeto(['Significant', progress]), verbo([has]), complemento([been, made, in, recent, years])]). relacion([sujeto(['New', tools, and, more, directed, approaches, will, help, answer, important, fundamental, questions, regarding, their, 'structure,', 'regulation,', and, 'function,', as, well, as, explore, their, potential, as]), verbo([targets]), complemento([for, selection, and, modification, for, improved, plant, performance, in, a, changing, environment])]). relacion([sujeto(['With', a, false, negative, rate, of, 18, '%', and, a, false, positive, rate, of, 12, '%', ',', this, method]), verbo([has]), complemento([similar, performance, as, other, 'RNAi', screens, in, the, 'well-described', 'Drosophila', model, system])]). relacion([sujeto(['In', a, separate, 'experiment,', we, screened, 26, uncharacterized, genes, computationally, predicted, to, be, essential, for, spermatogenesis, and]), verbo([found]), complemento([numerous, candidates, for, follow, up, studies])]). relacion([sujeto(['The', experimental, protocols, and, analysis, scripts]), verbo([provided]), complemento([will, enable, other, groups, to, use, this, procedure, to, study, diverse, aspects, of, germ, cell, biology, ranging, from, epigenetics, to, cell, physiology])]). relacion([sujeto(['This', approach, also]), verbo([has]), complemento([great, promise, as, an, applied, tool, for, validating, diagnoses, made, from, medical, genome, 'sequencing,', or, designing, synthetic, biological, sequences, that, act, as, potent, and, highly, specific, male, contraceptives])]). relacion([sujeto(['Globally,', forests, represent, highly, productive, ecosystems, that]), verbo([act]), complemento([as, carbon, sinks, where, soil, organic, matter, is, formed, from, residuals, after, biomass, decomposition, as, well, as, from, rhizodeposited, carbon])]). relacion([sujeto(['Fungi,', bacteria, and, archaea, inhabit, various, forest, 'habitats:', 'foliage,', the, wood, of, living, 'trees,', the, bark, 'surface,', ground, 'vegetation,', roots, and, the, 'rhizosphere,', 'litter,', 'soil,', 'deadwood,', rock, 'surfaces,', 'invertebrates,', wetlands, or, the, 'atmosphere,', each, of, which]), verbo([has]), complemento([its, own, specific, 'features,', such, as, nutrient, availability, or, temporal, dynamicy, and, specific, drivers, that, affect, microbial, 'abundance,', the, level, of, dominance, of, bacteria, or, fungi, as, well, as, the, composition, of, their, communities])]). relacion([sujeto(['Although', 'Clonorchis', sinensis, lives, in, the, bile, 'duct,', few, studies]), verbo([have]), complemento([investigated, the, local, immune, response, in, the, liver, and, bile, duct])]). relacion([sujeto(['Recovery', rates, were, 80.0, '%', and, 73.0, '%', in, 'PI', 1, w, and, 'PI', 4, w, 'mice,', 'respectively,', but, significantly]), verbo([decreased]), complemento([during, 're-infection', to, 26.6, '%', in, 'RI', 1, w, and, 13.3, '%', in, 'RI', 4, w])]). relacion([sujeto(['This', result]), verbo([suggested]), complemento([that, the, mice, were, resistant, to, 're-infection'])]). relacion([sujeto(['Kupffer', cells]), verbo([expressed]), complemento(['Th2-related', cytokines, '(', 'IL-10', and, 'IL-13)', during, primary, infection])]). relacion([sujeto(['sinensis-specific', 'IgG1', and, 'IgG2a', strongly]), verbo([increased]), complemento([in, 'RI', 1, w, mice])]). relacion([sujeto(['sinensis,', 'Kupffer', cells, likely]), verbo([act]), complemento([as, 'antigen-presenting', 'cells,', stimulating, the, 'Th2', cytokine, production, system])]). relacion([sujeto(['Two', members, of, the, genus, 'beta,', 'HPV5', and, 'HPV8,', were, first, identified, in, patients, with, a, genetic, 'disorder,', epidermodysplasia, verruciformis, '(', 'EV),', that]), verbo([confers]), complemento([high, susceptibility, to, beta, 'HPV', infection, and, 'NMSC', development])]). relacion([sujeto(['The', fact, that, organ, transplant, recipients, '(', 'OTRs)', with, an, impaired, immune, system]), verbo([have]), complemento([an, elevated, risk, of, 'NMSC', raised, the, hypothesis, that, beta, 'HPV', types, may, also, be, involved, in, skin, carcinogenesis, in, 'non-EV', patients])]). relacion([sujeto(['Epidemiological', studies]), verbo([have]), complemento([shown, that, serological, and, viral, 'DNA', markers, are, 'weakly,', but, 'significantly,', associated, with, history, of, 'NMSC', in, 'OTRs', and, the, general, population])]). relacion([sujeto(['Functional', studies, on, mucosal, 'high-risk', '(', 'HR)', 'HPV', types]), verbo([have]), complemento([clearly, demonstrated, that, the, products, of, two, early, 'genes,', 'E6', and, 'E7,', are, the, main, viral, 'oncoproteins,', which, are, able, to, deregulate, events, closely, linked, to, 'transformation,', such, as, cell, cycle, progression, and, apoptosis])]). relacion([sujeto(['Studies', on, a, small, number, of, beta, 'HPV', types]), verbo([have]), complemento([shown, that, their, 'E6', and, 'E7', oncoproteins, also, have, the, ability, to, interfere, with, the, regulation, of, key, 'pathways/events', associated, with, cellular, transformation])]). relacion([sujeto(['However,', the, initial, functional, data, indicate, that, the, molecular, mechanisms]), verbo([leading]), complemento([to, cellular, transformation, are, different, from, those, of, mucosal, 'HR', 'HPV', types])]). relacion([sujeto(['Beta', 'HPV', types, may]), verbo([act]), complemento([only, at, early, stages, of, 'carcinogenesis,', by, potentiating, the, deleterious, effects, of, other, 'carcinogens,', such, as, 'UV', radiation])]). relacion([sujeto(['As', a, physical, 'barrier,', the, insect, cuticle]), verbo([provides]), complemento([a, key, resistance, 'trait,', and, 'Tenebrio', molitor, shows, phenotypic, variation, in, cuticular, colour, that, correlates, with, resistance, to, the, entomopathogenic, fungus, 'Metarhizium', anisopliae])]). relacion([sujeto(['Second,', we, tested, the, hypothesis, that, 'tyrosine,', a, 'semi-essential', amino, acid]), verbo([required]), complemento([for, immune, defence, and, cuticular, melanisation, and, 'sclerotisation,', can, act, as, a, limiting, resource, by, supplementing, the, larval, diet, and, subsequently, examining, adult, cuticular, colouration, and, thickness])]). relacion([sujeto(['We']), verbo([found]), complemento([that, stock, beetles, and, beetles, artificially, selected, for, extremes, of, cuticular, colour, had, thicker, less, porous, cuticles, when, they, were, 'darker,', and, thinner, more, porous, cuticles, when, they, were, 'lighter,', showing, that, colour, 'co-varies', with, two, architectural, cuticular, features])]). relacion([sujeto(['Experimental', supplementation, of, the, larval, diet, with, tyrosine]), verbo([led]), complemento([to, the, development, of, darker, adult, cuticle, and, affected, thickness, in, a, 'sex-specific', manner])]). relacion([sujeto(['The', results, of, this, study]), verbo([provide]), complemento([a, mechanism, for, maintenance, of, cuticular, colour, variation, in, this, species, of, 'beetle;', darker, cuticles, are, 'thicker,', but, their, production, is, potentially, limited, by, resource, constraints, and, differential, investments, in, resistance, mechanisms, between, the, sexes])]). relacion([sujeto(['Managing', ecosystems, to]), verbo([provide]), complemento([ecosystem, services, in, the, face, of, global, change, is, a, pressing, challenge, for, policy, and, science])]). relacion([sujeto(['Failure', to, understand, those, interactions, can]), verbo([lead]), complemento([to, detrimental, outcomes, from, management, decisions])]). relacion([sujeto(['Network', theory, that, integrates, ecological, and, socioeconomic, systems, may]), verbo([provide]), complemento([a, path, to, meeting, this, challenge])]). relacion([sujeto(['While', network, theory, offers, promising, approaches, to, examine, ecosystem, 'services,', few, studies]), verbo([have]), complemento([identified, how, to, operationalize, networks, for, managing, and, assessing, diverse, ecosystem, services])]). relacion([sujeto(['However,', synergistic, effects, of, 'CTX', and, 'ACT', on, the, 'spatio-temporal', dynamics, of, immunocytes, in, vivo]), verbo([have]), complemento([not, been, described])]). relacion([sujeto(['Here,', we, visualized, key, cell, events, of, 'immunotherapy-elicited', immunoreactions, in, a, 'multicolor-coded', tumor, 'microenvironment,', and, then, established, an, optimal, strategy, of, metronomic, 'combined-immunotherapy', to]), verbo([enhance]), complemento(['anti-tumor', efficacy])]). relacion([sujeto(['The', 'CTX-ACT', 'combined-treatment', elicited, synergistic, immunoreactions, in, tumor, 'areas,', which, included, relieving, the, immune, 'suppression,']), verbo([triggering]), complemento([the, transient, activation, of, endogenous, 'tumor-infiltrating', 'immunocytes,', increasing, the, accumulation, of, adoptive, cytotoxic, 'T', 'lymphocytes,', and, accelerating, the, infiltration, of, dendritic, cells])]). relacion([sujeto(['These', insights, into, the, 'spatio-temporal', dynamics, of, immunocytes, are, beneficial, for, optimizing, immunotherapy, and]), verbo([provide]), complemento([new, approaches, for, elucidating, the, mechanisms, underlying, the, involvement, of, immunocytes, in, cancer, immunotherapy])]). relacion([sujeto(['Using', a, chemical, rescue, 'approach,', we, previously, identified, compounds]), verbo([targeting]), complemento(['Plasmodium', falciparum, coenzyme, 'A', '(', 'CoA)', synthesis, or, 'utilization,', a, promising, target, that, has, not, yet, been, exploited, in, 'anti-malarial', drug, development])]). relacion([sujeto(['We']), verbo([report]), complemento([on, the, outcomes, of, a, series, of, biological, tests, that, help, to, define, the, 'species-', and, 'stage-specificity,', as, well, as, the, potential, targets, of, these, chemically, diverse, compounds])]). relacion([sujeto(['Chemical', rescue, profiling, with, 'CoA', pathway, intermediates, demonstrated, that, most, compounds]), verbo([acted]), complemento([on, either, of, the, two, final, 'P'])]). relacion([sujeto(['The', most, active, compound]), verbo([targeted]), complemento([either, phosphopantothenoylcysteine, synthetase, '(', 'PPCS)', or, phosphopantothenoylcysteine, decarboxylase, '(', 'PPCDC)'])]). relacion([sujeto([cruzi, amastigotes, was, 'observed;', however, three, compounds]), verbo([inhibited]), complemento([the, viability, of, trypomastigotes, with, 'sub-micromolar', potencies, and, were, confirmed, to, act, on, 'T'])]). relacion([sujeto(['Furthermore,', three, compounds]), verbo([inhibited]), complemento([the, viability, of, 'T'])]). relacion([sujeto([brucei, trypomastigotes, with, 'sub-micromolar', potencies, and, were, confirmed, to]), verbo([act]), complemento([on, 'T'])]). relacion([sujeto([brucei, 'CoA', 'synthesis,', indicating, that, the, 'CoA', synthesis, pathway, might, represent, a, valuable, new, drug]), verbo([target]), complemento([in, these, parasite, species])]). relacion([sujeto(['Two', recently, identified, key, pathways]), verbo([involve]), complemento([the, kinases, mechanistic, target, of, rapamycin, '(', 'mTOR)', and, 'mitogen-activated', protein, kinases, '(', 'MAPK)'])]). relacion([sujeto(['Interestingly,', mRNAs, coding, for, those, biomarkers, are]), verbo([found]), complemento([to, be, localized, at, or, near, synapses, indicating, a, local, misregulation, of, synthesis, and, activity])]). relacion([sujeto(['Research', in, the, last, decade, indicates, that, 'RNA-binding', proteins, '(', 'RBPs)', responsible, for, mRNA, 'localization,', stability, and, translation]), verbo([mediate]), complemento([local, expression, control])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, 'mTOR/MAPK', act, on, 'RBPs', to, regulate, the, fate, of, 'mRNAs,', indicating, a, misregulation, of, protein, expression, at, synapses, in, epilepsy])]). relacion([sujeto(['We', propose, that, mTOR, and, 'MAPK']), verbo([regulate]), complemento(['RBPs,', thereby, guiding, the, local, expression, of, their, 'target-mRNAs', encoding, for, markers, of, epilepsy])]). relacion([sujeto(['Thus,', misregulated, 'mTOR/MAPK-RBP', interplay, may, result, in, excessive, local, synthesis, of, ion, channels, and, receptors, thereby]), verbo([leading]), complemento([to, hyperexcitability])]). relacion([sujeto(['Continuous', stimulation, of, synapses, further]), verbo([activates]), complemento(['mTOR/MAPK', pathway, reinforcing, their, effect, on, 'RBP-mediated', expression, control, establishing, the, basis, for, epilepsy])]). relacion([sujeto(['Global', prioritization, of, 'single-disease', eradication, programs, over, improvements, to, basic, diagnostic, capacity, in, the, 'Global', 'South']), verbo([have]), complemento([left, the, world, unprepared, for, epidemics, of, 'chikungunya,', 'Ebola,', 'Zika,', and, whatever, lies, on, the, horizon])]). relacion([sujeto(['Malaria', is, the, most, common, diagnosis, for, febrile, patients, in, 'low-resource', health, care, 'settings,', and, malaria, misdiagnosis]), verbo([has]), complemento([soared, due, to, the, institutionalization, of, malaria, as, the, primary, febrile, illness, of, 'SSA', by, international, development, organizations, and, national, malaria, control, programs])]). relacion([sujeto(['This']), verbo([has]), complemento([inadvertently, created, a, &, 'quot;malaria-industrial', 'complex"', and, historically, obstructed, our, complete, understanding, of, the, 'continent\'s', complex, communicable, disease, 'epidemiology,', which, is, currently, dominated, by, a, mélange, of, undiagnosed, febrile, illnesses])]). relacion([sujeto(['We', synthesize, interdisciplinary, literature, from, 'Ghana', to, highlight, the, complexity, of, communicable, disease, care, in, 'SSA', from, 'biomedical,', 'social,', and, environmental, 'perspectives,', and]), verbo([suggest]), complemento([a, way, forward])]). relacion([sujeto(['A', 'socio-environmental', approach, to, acute, febrile, illness, 'etiology,', 'diagnostics,', and, management, would]), verbo([lead]), complemento([to, substantial, health, gains, in, 'Africa,', including, more, efficient, malaria, control])]). relacion([sujeto(['Dysregulation', of, histone, methylation]), verbo([has]), complemento([emerged, as, a, major, driver, of, neurodevelopmental, disorders, including, intellectual, disabilities, and, autism, spectrum, disorders])]). relacion([sujeto(['Histone', methyl, writer, and, eraser, enzymes, generally]), verbo([act]), complemento([within, multisubunit, complexes, rather, than, in, isolation])]). relacion([sujeto(['Histone', 'H3K4', methylation, '(', 'H3K4me)', is, a, chromatin, signature]), verbo([associated]), complemento([with, active, 'gene-regulatory', elements])]). relacion([sujeto(['We', review, a, body, of, literature, that, supports, a, model, in, which, the, 'RAI1-containing', 'H3K4me', writer, complex, counterbalances, the, 'LSD1-containing', 'H3K4me', eraser, complex, to]), verbo([ensure]), complemento([normal, brain, development])]). relacion([sujeto(['For', lung, adenocarcinoma, '(', 'LUAD)', patients, receiving, 'platinum-based', adjuvant, chemotherapy, '(', 'ACT),', predictive, signatures, extracted, from, survival, data, solely, are, not, directly]), verbo([associated]), complemento([with, platinum, response])]). relacion([sujeto(['Another', limitation, of]), verbo([reported]), complemento(['signatures,', commonly, based, on, risk, scores, summarised, from, gene, 'expressions,', is, that, they, could, not, be, applied, directly, to, samples, measured, by, different, laboratories, due, to, experimental, batch, effects])]). relacion([sujeto(['Using', 60, samples, of, 'LUAD', patients, receiving, 'platinum-based', 'ACT', in, 'TCGA,', we, 'pre-selected', gene, pairs, whose, 'within-samples', relative, expression, orderings, '(', 'REOs)', were, significantly]), verbo([associated]), complemento([with, both, pathological, response, and, 5, -, year, 'survival,', from, which, we, selected, an, optimal, signature, whose, 'within-samples', 'REOs', could, identify, responders, with, improved, 5, -, year, survival, rate])]). relacion([sujeto(['HMGA1', is, a, 'non-histone']), verbo([nuclear]), complemento([protein, that, regulates, cellular, 'proliferation,', invasion, and, apoptosis, and, is, overexpressed, in, many, carcinomas])]). relacion([sujeto(['Four', liver, cancer, cell, lines, with, stable]), verbo([induced]), complemento([or, knockdown, expression, of, 'HMGA1', were, characterized, using, in, vitro, 'assays,', including, 'proliferation,', migration, and, 'anchorage-independent', growth])]). relacion([sujeto(['HMGA1', expression]), verbo([increased]), complemento([monotonically, from, normal, liver, tissues, to, cirrhotic, tissue, to, 'HCC', '(', 'P<'])]). relacion([sujeto([1, ')', and, was]), verbo([associated]), complemento([with, 'Edmondson', grade, '(', 'P<'])]). relacion([sujeto(['Overall,', 51, '%', and, 42, '%', of, 'HCCs', and, cirrhotic, tissues]), verbo([expressed]), complemento(['HMGA1,', respectively])]). relacion([sujeto(['Forced', expression, of, 'HMGA1', in, liver, cancer, models, resulted, in]), verbo([increased]), complemento([cell, growth, and, 'migration,', and, vice, versa])]). relacion([sujeto(['Soft', agar, assay, showed, that, forced, expression, of, 'HMGA1']), verbo([led]), complemento([to, increased, foci, 'formation,', suggesting, an, oncogenic, role, of, 'HMGA1', in, hepatocarcinogenesis])]). relacion([sujeto(['HMGA1', is, frequently]), verbo([expressed]), complemento([in, cirrhotic, tissues, and, 'HCCs', and, its, expression, is, associated, with, high, 'Edmondson', grade, and, worse, prognosis, in, 'HCC'])]). relacion([sujeto(['Our', results]), verbo([suggest]), complemento([that, 'HMGA1', may, act, as, oncogenic, driver, of, 'progression,', implicating, it, in, tumor, growth, and, migration, potential, in, liver, carcinogenesis])]). relacion([sujeto(['Transport', experiments, in, 'biofilm-coated', sand, showed, that, 'biofilms,', irrespective, of, bacterial, 'species,', significantly]), verbo([inhibited]), complemento([the, mobility, of, 'GONPs', compared, to, that, in, cleaned, sand])]). relacion([sujeto(['This', could, be, due, to, the, 'Ca(2+)', 'complexation,']), verbo([increased]), complemento([surface, roughness, and, charge, heterogeneities, of, 'collectors,', and, particularly, enhanced, physical, straining, caused, by, biofilms])]). relacion([sujeto(['The', 'two-site', kinetic, retention, 'model-fitted', value, of, maximum, 'solid-phase', concentration, '(', 'Smax2)', for, 'GONPs', was, higher, for, 'biofilm-coated', sand, than, for, cleaned, 'sand,', demonstrating, that, biofilms]), verbo([act]), complemento([as, favorable, sites, for, 'GONPs', retention])]). relacion([sujeto(['Pemphigus', is, an, autoimmune, disease, that]), verbo([causes]), complemento([blistering, and, is, 'life-threatening', if, left, untreated])]). relacion([sujeto(['Nowadays,']), verbo([finding]), complemento([a, promising, treatment, for, pemphigus, remains, a, serious, challenge])]). relacion([sujeto(['Various', treatments, are, currently, recommended, to, treat, this, 'disease,', but, they, rarely]), verbo([lead]), complemento([to, complete, and, durable, remission])]). relacion([sujeto(['Regulatory', cells, appear, to]), verbo([have]), complemento([a, critical, role, in, numerous, autoimmune, 'diseases,', so, it, is, possible, that, promotion, of, these, cells, may, induce, remission])]). relacion([sujeto(['This', study, presents, a, new, approach, to, treating, pemphigus, that]), verbo([has]), complemento([not, been, discussed, to, date])]). relacion([sujeto(['This', cytokine, could]), verbo([induce]), complemento([two, different, types, of, regulatory, 'cell,', including, 'IL-35-that', produces, induced, regulatory, 'T', cells, and, 'IL-35(+)', regulatory, 'B', 'cells,', which, could, suppress, both, effector, 'T', cells, and, effector, 'B', cells])]). relacion([sujeto(['It', seems, that, 'IL-35', may]), verbo([act]), complemento([as, an, efficient, therapeutic, strategy, for, pemphigus])]). relacion([sujeto(['However,', further, study, is]), verbo([required]), complemento([to, evaluate, the, efficacy, and, safety, of, treating, pemphigus, with, 'IL-35'])]). relacion([sujeto(['As', 'US', public, health, faces]), verbo([increasing]), complemento([threats, from, 'outbreaks,', impending, changes, to, the, healthcare, landscape, in, the, 'United', 'States', may, alter, the, way, that, health, departments, are, able, to, detect, and, control, some, of, the, most, common, infectious, diseases])]). relacion([sujeto(['The', 'Patient', 'Protection', and, 'Affordable', 'Care', 'Act', '(', 'ACA)']), verbo([has]), complemento([made, significant, changes, in, the, way, health, care, is, provided, in, the, 'United', 'States'])]). relacion([sujeto(['While', many, of, the, 'clinical,', 'economic,', and, policy, implications, of, the, 'ACA', are, well, 'described,', there]), verbo([has]), complemento([been, limited, analysis, of, 'changes,', if, 'any,', in, the, surveillance, and, control, of, infectious, diseases, of, public, health, 'importance-such', as, 'tuberculosis,', sexually, transmitted, 'infections,', and, 'HIV-that', are, anticipated, or, occurring, as, the, 'ACA', is, implemented, across, the, 'United', 'States'])]). relacion([sujeto(['This', analysis, identifies, several, ways, in, which, 'ACA', implementation]), verbo([has]), complemento([not, fully, addressed, the, public, health, needs, associated, with, 'diagnosis,', 'treatment,', 'surveillance,', and, control, of, infectious, diseases, of, public, health, importance])]). relacion([sujeto(['Expression', of, 'wild-type', protein, tyrosine, phosphatase, '(', 'PTP)', 1, 'B', may]), verbo([act]), complemento([either, as, a, tumor, suppressor, by, dysregulation, of, protein, tyrosine, kinases, or, a, tumor, promoter, through, 'Src', dephosphorylation, at, 'Y527', in, human, breast, cancer, cells])]). relacion([sujeto(['To', explore, whether, mutated, 'PTP1B', is]), verbo([involved]), complemento([in, human, 'carcinogenesis,', we, have, sequenced, 'PTP1B', cDNAs, from, human, tumors, and, found, splice, mutations, in, '~20%', of, colon, and, thyroid, tumors])]). relacion([sujeto(['The', 'PTP1BΔE6', mutant]), verbo([expressed]), complemento([in, these, two, tumor, types, and, another, 'PTP1BΔE5', mutant, expressed, in, colon, tumor, were, studied, in, more, detail])]). relacion([sujeto(['Although', 'PTP1BΔE6', revealed, no, phosphatase, activity, compared, with, 'wild-type', 'PTP1B', and, the, 'PTP1BΔE5', 'mutant,', its, expression]), verbo([induced]), complemento([oncogenic, transformation, of, rat, fibroblasts, without, 'Src', 'activation,', indicating, that, it, involved, signaling, pathways, independent, of, 'Src'])]). relacion([sujeto(['The', transformed, cells, were, tumourigenic, in, nude, 'mice,']), verbo([suggesting]), complemento([that, the, 'PTP1BΔE6', affected, other, 'molecule(s)', in, the, human, tumors])]). relacion([sujeto(['These', observations, may]), verbo([provide]), complemento([a, novel, therapeutic, target, for, colon, and, thyroid, cancer])]). relacion([sujeto(['The', precursor, sites, composed, of, wide, 'O-Si-O', bond, angles, in, amorphous, 'SiO2']), verbo([act]), complemento([as, deep, electron, traps, and, can, accommodate, up, to, two, extra, electrons])]). relacion([sujeto(['This', mechanism, may]), verbo([have]), complemento([important, implications, for, our, understanding, of, dielectric, breakdown, and, resistance, switching, in, 'a-SiO2', based, electronic, and, memory, devices])]). relacion([sujeto(['The', 'Care', 'Act', 2014]), verbo([has]), complemento([placed, a, responsibility, on, local, authorities, in, 'England', to, provide, services, that, prevent, deterioration, and, minimise, the, use, of, other, health, and, social, care, services])]). relacion([sujeto(['Housing', adaptations]), verbo([have]), complemento([been, identified, as, 1, of, the, 10, most, promising, prevention, services, for, older, 'adults,', with, bathing, adaptations, being, the, most, requested])]). relacion([sujeto(['However,', many, local, authorities]), verbo([have]), complemento([lengthy, waiting, times, which, may, increase, 'costs,', reduce, effectiveness, and, reduce, the, preventive, effect])]). relacion([sujeto(['The', 'RCT', will]), verbo([recruit]), complemento([between, 40, and, 60, people, who, have, been, referred, for, an, accessible, showering, 'facility,', and, their, 'carers,', from, 1, local, authority, in, 'England'])]). relacion([sujeto(['Favourable', ethical, opinion, was]), verbo([provided]), complemento([by, the, 'Social', 'Care', 'Research', 'Ethics', 'Committee', '(', reference, number, 16, /, 'IEC08/0017)'])]). relacion([sujeto(['This', would, investigate, the, effect, of, bathing, adaptations, on, quality, of, life, and, whether]), verbo([increased]), complemento([waiting, times, are, associated, with, poorer, outcomes, and, increased, costs])]). relacion([sujeto(['The', results]), verbo([have]), complemento([further, potential, to, inform, trials, of, other, housing, or, social, care, interventions, using, the, novel, waiting, list, control, method])]). relacion([sujeto(['Participant', responses]), verbo([reveal]), complemento([that, 'where,', 'when,', who, and, how, a, primary, health, professional, conducted, the, 75, +, 'HA', affected, what, older, people, talked, 'about,', the, guidance, they, sought, to, deal, with, issues, 'and,', in, 'turn,', the, actioning, of, issues, that, were, discussed, during, the, 75, +, 'HA'])]). relacion([sujeto(['Conclusion', 'To', enable, older, people, to, make, informed, decisions, about, and, successfully, manage, their, own, health, and, well, 'being,', and, to, choose, when, to, invite, others, to]), verbo([act]), complemento([on, their, 'behalf,', primary, health, professionals, need, to, ask, questions, in, the, 75, +, 'HA', within, a, 'person-centred', mindset])]). relacion([sujeto(['The', 75, +, 'HA', is, an, opportunity, to]), verbo([ensure]), complemento([older, people, know, why, they, need, 'support,', which, 'ones,', and, agree, 'to,', supports, and, services, they, require])]). relacion([sujeto(['What', does, this, paper, 'add?', 'There', is, 'scant,', if, 'any,', attention, in, the, literature, to, the, views, of, consumers, who]), verbo([have]), complemento([completed, a, 75, +, 'HA,', especially, with, regard, to, whether, this, opportunity, is, conducted, with, a, 'person-centred', mindset])]). relacion([sujeto(['Even', after]), verbo([participating]), complemento([in, the, 75, +, 'HA,', most, participants, were, unclear, as, to, the, purpose, of, the, 'assessment,', what, information, had, been, recorded, and, what, would, happen, from, any, concerns, identified, in, the, assessment])]). relacion([sujeto(['Comments', about, the, 75, +, 'HA', included, that, it, did, not, ask, people, about, their, goals, and, what, comprised, their, functionality, to]), verbo([ensure]), complemento([their, independent, living])]). relacion([sujeto(['What', are, the, implications, for, 'practitioners?', 'A', 'person-centred', approach]), verbo([requires]), complemento([active, collaboration, between, primary, health, professionals, and, older, people, who, are, living, the, process, 'of,', and, planning, 'for,', 'aging-in-place'])]). relacion([sujeto(['Practitioners', need, to, ask, questions, of, older, people, and]), verbo([respond]), complemento([to, what, they, say, with, a, 'person-centred', mindset])]). relacion([sujeto(['Texas']), verbo([has]), complemento([experienced, a, roughly, 6, -, 'percentage-point', increase, in, insurance, coverage, '(', from, 74.7, '%', to, 80.6, '%', ;, 'P', =])]). relacion([sujeto(['The', 4, subgroups, with, the, largest]), verbo([increases]), complemento([in, adjusted, insurance, coverage, between, 2013, and, 2016, were, persons, aged, 50, to, 64, years, '(', 12.1, percentage, 'points;', 'P', =])]). relacion([sujeto([2, ')', ',', persons]), verbo([reporting]), complemento([fair, or, poor, health, status, '(', 10.2, percentage, 'points;', 'P', =])]). relacion([sujeto(['Many', population, subgroups]), verbo([have]), complemento([benefited, from, the, 'ACA\'s', 'Marketplace,', but, approximately, 3, million, 'Texas', residents, still, lack, health, coverage])]). relacion([sujeto(['The']), verbo([release]), complemento([of, neutrophil, extracellular, traps, '(', 'NETs)', is, a, major, immune, mechanism, intended, to, capture, pathogens])]). relacion([sujeto(['These', histone, and, 'protease-coated', 'DNA', structures, are]), verbo([released]), complemento([by, neutrophils, in, response, to, a, variety, of, 'stimuli,', including, respiratory, 'pathogens,', and, have, been, identified, in, the, airways, of, patients, with, respiratory, 'infection,', cystic, 'fibrosis,', acute, lung, 'injury,', primary, graft, dysfunction, and, 'COPD'])]). relacion([sujeto(['NET', production]), verbo([has]), complemento([been, demonstrated, in, the, lungs, of, mice, infected, with, 'Staphylococcus', 'aureus,', 'Klebsiella', pneumoniae, and, 'Aspergillus', fumigatus])]). relacion([sujeto(['Since', the, discovery, of, 'NETs', over, a, decade, 'ago,', evidence, that, &, 'quot;NET', 'evasion"', might]), verbo([act]), complemento([as, a, immune, protection, strategy, among, respiratory, pathogens, including, group, 'A', 'Streptococcus,', 'Bordetella', 'pertussis,', and, 'Haemophilus', influenzae, has, been, 'growing,', with, the, majority, of, these, studies, being, published, in, the, past, two, years])]). relacion([sujeto(['Evasion', strategies, fall, into, three, main, 'categories:', inhibition, of, 'NETs']), verbo([release]), complemento([by, 'down-regulating', host, inflammatory, 'responses,', degradation, of, 'NETs', using, 'pathogen-derived', 'deoxyribonucleases,', and, resistance, to, the, microbicidal, components, of, 'NETs,', which, involves, a, variety, of, mechanisms, including, encapsulation])]). relacion([sujeto(['State', licensing, boards]), verbo([have]), complemento([obligations, to, protect, the, public, from, impaired, professionals, and, to, protect, the, rights, of, professionals, applying, for, licensure])]). relacion([sujeto(['Competently', functioning, professionals, who]), verbo([have]), complemento([or, have, had, a, mental, health, diagnosis, or, are, being, treated, for, a, mental, health, condition, should, not, be, screened, 'out,', according, to, the, 'Americans', with, 'Disabilities', 'Act', '(', 'ADA)'])]). relacion([sujeto(['For', 'comparison,', we, review, a, sample, of, licensure, applications, for, physicians, and, lawyers, and]), verbo([find]), complemento([a, similar, pattern])]). relacion([sujeto(['Five', of, the, present, authors, offer, ourselves, and, other, published, authors, as, examples, of, competent, licensed, psychologists, who]), verbo([have]), complemento([lived, with, mental, illnesses])]). relacion([sujeto(['Previous', studies, on, acceptance, and, commitment, therapy, '(', 'ACT)']), verbo([have]), complemento([shown, promising, results, in, improving, functioning, in, affected, 'children,', but, more, research, is, still, urgently, needed])]). relacion([sujeto(['Bariatric', surgery]), verbo([has]), complemento([serious, implications, on, metabolic, health])]). relacion([sujeto(['We', established, a, theoretical, model, of, how, impulsivity, is, related, to, weight]), verbo([loss]), complemento([outcome])]). relacion([sujeto(['We', propose, that, depressive, symptoms]), verbo([act]), complemento([as, a, mediator, between, impulsivity, and, pathological, eating, 'behavior,', and, that, pathological, eating, behavior, has, a, direct, impact, on, weight, loss, outcome])]). relacion([sujeto(['We', calculated, excessive, weight]), verbo([loss]), complemento(['(', '%', 'EWL)', and, assessed, 'self-reported', impulsivity, '(', using, the, 'Baratt', 'Impulsiveness', 'Scale', '(', 'BIS-15)', total, 'score),', depressive, symptoms, '(', the, 'Patient', 'Health', 'Questionnaire', '(', 'PHQ-9)', 'score),', and, pathological, eating, behavior, '(', the, 'Eating', 'Disorder', 'Inventory', 2, '(', 'EDI-2)', total, 'score)', in, 65, patients, four, years, after, laparoscopic, sleeve, gastrectomy])]). relacion([sujeto(['The', 'BIS-15,', 'PHQ-9,', and, 'EDI-2']), verbo([have]), complemento([medium, to, high, correlations, between, each, 'other,', and, 'EDI-2', correlated, with, '%', 'EWL'])]). relacion([sujeto([',']), verbo([suggest]), complemento([that, impulsivity, has, an, indirect, impact, on, weight, loss, outcome, after, bariatric, 'surgery,', mediated, by, depression, and, transferred, through, pathological, eating, behavior])]). relacion([sujeto(['Thus,', the, underlying, psychological, factors, should, be, addressed, in, 'post-operative', care, to, optimize, weight]), verbo([loss]), complemento([outcome])]). relacion([sujeto(['BK', virus, '(', 'BKV)-associated', nephropathy, is, the, second]), verbo([leading]), complemento([cause, of, graft, loss, in, kidney, transplant, recipients])]). relacion([sujeto(['Due', to, the, high, prevalence, of, persistent, infection, with, 'BKV', in, the, general, 'population,', it, is, possible, that, either, the, transplant, recipient, or, donor, may]), verbo([act]), complemento([as, the, source, of, virus, resulting, in, viruria, and, viremia])]). relacion([sujeto(['Although', several, studies]), verbo([suggest]), complemento([a, correlation, between, 'donor-recipient', serostatus, and, the, development, of, 'BK', 'viremia,', specific, risk, factors, for, 'BKV-related', complications, in, the, transplant, setting, remain, to, be, established])]). relacion([sujeto(['The', mechanistic]), verbo([target]), complemento([of, rapamycin, '(', 'mTOR)', is, an, evolutionary, conserved, protein, with, a, 'serine/threonine', kinase, activity, that, regulates, cell, 'growth,', 'proliferation,', 'motility,', 'survival,', protein, 'synthesis,', autophagy, and, transcription])]). relacion([sujeto(['Regulation', of, specific, mTOR, pathway, functions, depends, on, multiple, 'GTPases,', that]), verbo([act]), complemento([either, as, regulators, of, mTOR, protein, 'complexes,', coupling, energy, availability, with, mTORC1, 'activity,', or, as, downstream, effectors, of, both, mTORC1, and, mTORC2])]). relacion([sujeto(['We', discuss, in, vitro, and, in, vivo, data]), verbo([suggesting]), complemento([that, 'RHEB', can, function, as, an, inhibitor, of, mTOR, when, not, bound, to, 'GTP'])]). relacion([sujeto(['RHEB-1', itself, is]), verbo([regulated]), complemento([by, 'Rab', 'GDP', dissociation, inhibitor, 'β,', which, directly, binds, to, 'ATX-2'])]). relacion([sujeto(['Post-translational', modifications, of, histones, play, essential, roles, in]), verbo([regulating]), complemento([chromatin, structure, and, function])]). relacion([sujeto(['These', are, tightly]), verbo([regulated]), complemento([in, vivo, and, there, is, an, intricate, 'cross-talk', between, different, marks, as, they, are, recognized, by, specific, reader, modules, present, in, a, large, number, of, nuclear, factors])]). relacion([sujeto(['In', order, to, precisely, dissect, these, processes, in, vitro, native, reagents, like, purified, chromatin, and, histone, 'modifying/remodeling', enzymes, are]), verbo([required]), complemento([to, more, accurately, reproduce, physiological, conditions])]). relacion([sujeto(['The', vast, majority, of, these, enzymes, need, to, be, part, of, stable, multiprotein, complexes, with, cofactors, enabling, them, to]), verbo([act]), complemento([on, chromatin, substrates, 'and/or', read, specific, histone, marks])]). relacion([sujeto(['In', the, accompanying, 'chapter,', we]), verbo([have]), complemento([described, the, protocol, for, purification, of, native, chromatin, from, yeast, cells, '(', 'Chapter', 3, ')'])]). relacion([sujeto(['Purification', of, native, biological, material]), verbo([provides]), complemento([powerful, tools, for, the, functional, analysis, of, enzymes, and, proteins, in, chromatin])]). relacion([sujeto(['Moreover,', the, physiological, substrate, of, most, enzymes, that, modify, histones, is, chromatin, and, the, majority, of, these, enzymes, need, to, be, part, of, a, multiprotein, assembly, to, be, able, to]), verbo([act]), complemento([on, chromatin])]). relacion([sujeto(['Matrix', 'metalloproteinases-2', '(', 'MMP-2)', and, the, tissue, inhibitor, of, 'metalloproteinase-2', '(', 'TIMP-2),', may, presumably]), verbo([have]), complemento([an, important, role, on, the, invasion, and, metastatic, spread, of, malignancies, attributed, to, an, uncontrolled, degradation, of, the, extracellular, matrix, '(', 'ECM)'])]). relacion([sujeto(['Concomitant']), verbo([increase]), complemento([in, the, expression, of, 'TIMP-2', and, 'MMP-2', suggested, that, the, rate, of, 'MMP-2/TIMP-2', expression, is, a, better, marker, for, characterization, of, 'MMP-2', concentration])]). relacion([sujeto(['High', expression, 'and/or', activity, of, 'MMP-2', were, linked, with, poorer, survival, in, 'OSCC', 'cases,', while, 'TIMPs']), verbo([have]), complemento([been, shown, to, apparently, act, as, either, 'growth-stimulating', or, suppressor, factors, for, tumors])]). relacion([sujeto(['MPD', is, commonly, misused, in, 'non-ADHD', '(', 'normal)', youth, and, young, adults, both, as, a, recreational, drug, and, for, cognitive]), verbo([enhancing]), complemento([effects, to, improve, their, grades])]). relacion([sujeto(['MPD', is, known, to]), verbo([act]), complemento([on, the, reward, 'circuit;', including, the, caudate, nucleus, '(', 'CN)'])]). relacion([sujeto(['It']), verbo([has]), complemento([been, widely, shown, that, the, 'DA', system, plays, an, important, role, in, the, response, to, 'MPD', exposure])]). relacion([sujeto(['It', was, observed, that, selective, 'D1', 'DA', antagonist, '(', 'SCH-23390)', given, 30, &, 'nbsp;min', prior, to, the, last, 'MPD', exposure, at, 'ED11', partially, reduced, or]), verbo([prevented]), complemento([the, effect, induced, by, 'MPD', exposure, in, 'CN', neuronal, firing, rates, across, all, 'MPD', doses])]). relacion([sujeto(['Selective', 'D2', 'DA', antagonist, '(', 'raclopride)', resulted, in, less, obvious, 'trends;', some, 'CN', neuronal, firing, rates, exhibited, a, slight]), verbo([increase]), complemento([in, all, 'MPD', doses])]). relacion([sujeto(['Photoacids', on, the, basis, of, pyrenol]), verbo([have]), complemento([been, extensively, studied, in, the, past, 60, years])]). relacion([sujeto(['Another', derivative, can]), verbo([act]), complemento([as, a, 'three-color', sensor, for, a, wide, range, of, different, pH, values])]). relacion([sujeto(['Adoptive', 'T-cell', therapy, '(', 'ACT)', is, an, emerging, paradigm, in, which, 'T', cells, are, genetically, modified, to]), verbo([target]), complemento(['cancer-associated', antigens, and, eradicate, tumors])]). relacion([sujeto(['However,', challenges, treating, epithelial, cancers, with, 'ACT', reflect, antigen]), verbo([targets]), complemento([that, are, not, 'tumor-specific,', permitting, immune, damage, to, normal, 'tissues,', and, preclinical, testing, in, artificial, xenogeneic, 'models,', preventing, prediction, of, toxicities, in, patients])]). relacion([sujeto(['In', that, 'context,', 'mucosa-restricted', antigens]), verbo([expressed]), complemento([by, cancers, exploit, anatomical, compartmentalization, which, shields, mucosae, from, systemic, antitumor, immunity])]). relacion([sujeto(['This', shielding, may, be, amplified, with, 'ACT', platforms, employing, 'antibody-based', chimeric, antigen, receptors, '(', 'CARs),', which]), verbo([mediate]), complemento(['MHC-independent', 'recog-nition', of, antigens])]). relacion([sujeto(['GUCY2C', is, a, cancer, mucosa, antigen]), verbo([expressed]), complemento([on, the, luminal, surfaces, of, the, intestinal, mucosa, in, mice, and, 'humans,', and, universally, overexpressed, by, colorectal, 'tumors,', suggesting, its, unique, utility, as, an, 'ACT', target])]). relacion([sujeto(['T', cells]), verbo([expressing]), complemento(['CARs', directed, by, a, 'GUCY2C-specific', antibody, fragment, recognized, 'GUCY2C,', quantified, by, expression, of, activation, markers, and, cytokines])]). relacion([sujeto(['Investigating', the, factors]), verbo([regulating]), complemento([fish, condition, is, crucial, in, ecology, and, the, management, of, exploited, fish, populations])]). relacion([sujeto(['The', body, condition, of, cod, '(', 'Gadus', 'morhua)', in, the, 'Baltic', 'Sea']), verbo([has]), complemento([dramatically, decreased, during, the, past, two, 'decades,', with, large, implications, for, the, fishery, relying, on, this, resource])]). relacion([sujeto(['The', changes, in, cod, condition, related, to, feeding, 'opportunities,', driven, either, by, 'density-dependence', or, food, 'limitation,', along, the, whole, period, investigated, and, to, the, fivefold]), verbo([increase]), complemento([in, the, extent, of, hypoxic, areas, in, the, most, recent, 20, years])]). relacion([sujeto(['Hypoxic', areas, can]), verbo([act]), complemento([on, cod, condition, through, different, mechanisms, related, directly, to, species, 'physiology,', or, indirectly, to, behaviour, and, trophic, interactions])]). relacion([sujeto(['Our', analyses]), verbo([found]), complemento([statistical, evidence, for, an, effect, of, the, 'hypoxia-induced', habitat, compression, on, cod, condition, possibly, operating, via, crowding, and, 'density-dependent', processes])]). relacion([sujeto(['In', 'addition,', it]), verbo([has]), complemento([been, shown, that, strongly, preferred, stimuli, can, often, act, as, a, reward])]). relacion([sujeto(['Four', macaque, monkeys, performed, a, simple, choice, 'task,', in, which, two, stimuli, selected, randomly, from, among, the, 50, stimuli, were, simultaneously, presented, on, a, monitor, and, monkeys, were]), verbo([required]), complemento([to, choose, either, stimulus, by, eye, movements])]). relacion([sujeto(['Neurophysiological', studies, would, be, needed, to, examine, whether, these, features, of, visual, stimuli, produce, more, activation, in, neurons, that]), verbo([participate]), complemento([in, this, preference, judgment])]). relacion([sujeto(['Results:', 'All', the, treated, groups, showed, an]), verbo([increase]), complemento([in, microhardness, value, in, comparison, to, the, control, group])]). relacion([sujeto(['The', highest]), verbo([increase]), complemento([in, microhardness, was, seen, in, 'Group', 'F'])]). relacion([sujeto(['These', craters, and, porosities]), verbo([increased]), complemento([in, size, and, often, showed, glass, like, appearance, after, laser, irradiation])]). relacion([sujeto(['Conclusions:', 'It', can, be]), verbo([suggested]), complemento([by, means, of, present, study, that, 'Er,Cr:YSGG', laser, irradiation, alone, or, in, combination, with, fluoride, gel, is, an, effective, tool, to, provide, resistance, against, the, caries])]). relacion([sujeto(['Significantly', higher, resistance, '(', 'p<', 0.05, ')', was, seen, when, 'APF', gel, was, used, prior, to, 'Er,Cr:YSGG', laser, irradiation, and, this, combination, can]), verbo([act]), complemento([as, an, efficient, tool, for, prevention, against, dental, caries])]). relacion([sujeto(['The', underlying]), verbo([cause]), complemento([is, intestinal, stasis])]). relacion([sujeto(['Enterolithiasis', in, tuberculosis, can, be, due, to, the, presence, of, 'strictures,', intestinal, 'bands,', or, 'interbowel/parietal', 'adhesions,']), verbo([leading]), complemento([to, intestinal, stasis])]). relacion([sujeto(['Secondary', enterolithiasis, is, generally]), verbo([caused]), complemento([by, gallstones, or, renal, stones, migrating, to, the, gastrointestinal, tract, due, to, fistula, formation])]). relacion([sujeto(['During', 'stasis,', food, particles]), verbo([act]), complemento([as, a, nidus, and, calcium, salts, are, deposited, over, the, food, 'particles,', leading, to, stone, formation])]). relacion([sujeto(['The', patient, underwent, emergency, 'laparotomy,']), verbo([revealed]), complemento([2, strictures, in, the, distal, ileum, with, 15.24, cm, of, the, bowel, between, them, containing, a, 2, '×2', cm, enterolith])]). relacion([sujeto(['The', 'patient\'s', postoperative, recovery, was, 'fine,', and]), verbo([he]), complemento([wasdischarged, with, ileostomy, on, antitubercular, treatment, '(', after, 'histopathologicalconfirmation)'])]). relacion([sujeto(['The', incidence, and, prevalence, of, enterolithiasis]), verbo([has]), complemento([been, on, the, rise, recently, because, of, advancement, in, radiological, imaging, studies])]). relacion([sujeto(['Tropomyosin', receptor, kinase, 'C', '(', 'TrkC)']), verbo([targeted]), complemento(['ligand-photosensitizer', 'construct,', 'IYIY-diiodo-boron-dipyrromethene', '(', 'IYIY-I2-BODIPY)', and, its, scrambled, counterpart, 'YIYI-I2-BODIPY', have, been, prepared])]). relacion([sujeto(['IYIY-I2-BODIPY']), verbo([binds]), complemento(['TrkC', similar, to, 'neurotrophin-3', '(', 'NT-3),', and, 'NT-3', has, been, reported, to, modulate, immune, responses])]). relacion([sujeto(['This', prompted, us, to, investigate, the, immunological, impacts]), verbo([mediated]), complemento([by, 'IYIY-I2-BODIPY', in, 'pre-', and, 'post-PDT', conditions])]). relacion([sujeto(['We', demonstrated, that, 'IYIY-I2-BODIPY', '(', strong, 'response)', and, 'YIYI-I2-BODIPY', '(', weak, 'response)', at, 10, 'mg/kg,', but, not, 'I2-BODIPY', 'control,']), verbo([increased]), complemento([the, levels, of, 'IL-2,', 'IL-4,', 'IL-6', and, 'IL-17,', but, decreased, the, levels, of, systemic, immunoregulatory, mediators, 'TGF-β,', 'myeloid-derived', suppressor, cells, and, regulatory, 'T-cells'])]). relacion([sujeto(['Only', 'IYIY-I2-BODIPY']), verbo([enhanced]), complemento([the, 'IFN-γ(+)', and, 'IL-17(+)', 'T-lymphocytes,', and, delayed, tumor, growth, '(', '~20%', smaller, 'size)', in, mice, when, administrated, daily, for, 5, days])]). relacion([sujeto(['All', those, effects, were, observed, without, 'irradiation;', when, irradiated, '(', 520, 'nm,', 100, 'J/cm(2),', 160, 'mW/cm(2))', to, produce, 'PDT', effects, '(', 'drug-light', interval, 1, 'h),', 'IYIY-I2-BODIPY']), verbo([induced]), complemento([stronger, responses])]). relacion([sujeto(['IYIY-I2-BODIPY', alone, and, in, combination, with, 'PDT']), verbo([modulates]), complemento([the, immune, response, in, such, a, way, that, tumor, growth, is, suppressed])]). relacion([sujeto(['Unlike', immunosuppressive, conventional, 'chemotherapy,', 'IYIY-I2-BODIPY', can]), verbo([act]), complemento([as, an, 'immune-stimulatory', chemotherapeutic, agent, with, potential, applications, in, clinical, cancer, treatment])]). relacion([sujeto(['The', 'Affordable', 'Care', 'Act']), verbo([requires]), complemento([nonprofit, hospitals, to, collaborate, with, public, health, agencies, and, community, stakeholders, to, identify, and, address, community, health, needs])]). relacion([sujeto(['Using', a, case, study, 'approach,', the, authors]), verbo([provide]), complemento([a, historical, review, of, governmental, relationships, with, nonprofit, community, 'hospitals,', offer, a, case, study, application, for, implementing, legislative, mandates, and, community, benefit, 'requirements,', share, the, insights, they, garnered, on, their, journey, to, meet, the, 'mandates,', and, conclude, that, drawing, upon, the, existing, resources, in, the, community, and, using, current, community, assets, in, novel, ways, can, help, conserve, 'time,', and, also, 'financial,', 'material,', and, human, resources, in, meeting, legislative, mandates])]). relacion([sujeto(['Multiple', factors]), verbo([act]), complemento([simultaneously, on, plants, to, establish, complex, interaction, networks, involving, 'nutrients,', elicitors, and, metabolites])]). relacion([sujeto(['Metabolomics', offers, a, better, understanding, of, complex, biological, 'systems,', but, evaluating, the, simultaneous, impact, of, different, parameters, on, metabolic, pathways, that]), verbo([have]), complemento([many, components, is, a, challenging, task])]). relacion([sujeto(['We', therefore, developed, a, novel, approach, that, combines, experimental, 'design,', untargeted, metabolic, profiling, based, on, multiple, chromatography, systems, and, ionization, 'modes,', and, multiblock, data, 'analysis,', facilitating, the, systematic, analysis, of, metabolic, changes, in, plants]), verbo([caused]), complemento([by, different, factors, acting, at, the, same, time])]). relacion([sujeto(['Using', this, 'method,']), verbo([target]), complemento([geraniol, compounds, produced, in, transgenic, tobacco, cell, cultures, were, grouped, into, clusters, based, on, their, response, to, different, factors])]). relacion([sujeto(['We', hypothesized, that, our, novel, approach, may]), verbo([provide]), complemento([more, robust, data, for, process, optimization, in, plant, cell, cultures, producing, any, target, secondary, 'metabolite,', based, on, the, simultaneous, exploration, of, multiple, factors, rather, than, varying, one, factor, each, time])]). relacion([sujeto(['The', suitability, of, our, approach, was, verified, by, confirming, several, previously]), verbo([reported]), complemento([examples, of, 'elicitor-metabolite', crosstalk])]). relacion([sujeto(['However,', unravelling, all, 'factor-metabolite', networks, remains, challenging, because, it]), verbo([requires]), complemento([the, identification, of, all, biochemically, significant, metabolites, in, the, metabolomics, dataset])]). relacion([sujeto(['Low', input, and, high, utilisation, can, strengthen, 'bottom-up', pathways, and]), verbo([enhance]), complemento([consumer, biomass, and, abundance])]). relacion([sujeto(['However,', if, inputs, exceed, utilisation, 'rates,', dung, can, 'accumulate,']), verbo([leading]), complemento([to, a, decline, in, water, 'quality,', with, important, repercussions, for, resident, assemblages])]). relacion([sujeto(['The', system, supports, over, a, thousand, 'hippos,', and, during, recent, drought, periods, '(', extending, over, a, 'decade),', hippo, dung]), verbo([has]), complemento([been, observed, to, form, mats, over, benthic, habitats])]). relacion([sujeto(['Our', findings]), verbo([suggest]), complemento([that, persistent, inputs, of, hippo, dung, can, act, as, an, important, stressor, of, benthic, 'systems,', leading, ultimately, to, a, loss, of, productivity])]). relacion([sujeto(['Its', psychopathological, model, is, based, on, the, idea, that, mainly, the, 'person\'s', regulatory, efforts, of, their, own, thoughts, and, feelings]), verbo([lead]), complemento([to, psychological, problems])]). relacion([sujeto(['The', present, article, aims, to]), verbo([provide]), complemento([a, comprehensive, description, of, 'ACT', in, 'Hungarian:', its, theoretical, 'background,', clinical, 'techniques,', and, efficacy])]). relacion([sujeto(['Membrane', localized, proteins, perceive, and]), verbo([respond]), complemento([to, biotic, and, abiotic, stresses])]). relacion([sujeto(['Single', 'T-DNA', insertion, lines, in, 'CRK28', and, 'CRK29,', two, 'CRKs']), verbo([induced]), complemento([in, response, to, flagellin, 'perception,', did, not, exhibit, robust, alterations, in, immune, responses])]). relacion([sujeto(['In', 'contrast,', silencing, multiple, bacterial, 'flagellin-induced', 'CRKs', resulted, in]), verbo([enhanced]), complemento([susceptibility, to, pathogenic, 'Pseudomonas', 'syringae,', indicating, functional, redundancy, in, this, large, gene, family])]). relacion([sujeto(['Enhanced', expression, of, 'CRK28', in, 'Arabidopsis']), verbo([increased]), complemento([disease, resistance, to, 'P'])]). relacion([sujeto([benthamiana]), verbo([induced]), complemento([cell, 'death,', which, required, intact, extracellular, cysteine, residues, and, a, conserved, kinase, active, site])]). relacion([sujeto(['CRK28-mediated', cell, death]), verbo([required]), complemento([the, common, 'RLK', 'co-receptor', 'BAK1'])]). relacion([sujeto(['CRK28']), verbo([associated]), complemento([with, 'BAK1', as, well, as, the, activated, 'FLS2', immune, receptor, complex])]). relacion([sujeto(['CRK28', 'self-associated', as, well, as]), verbo([associated]), complemento([with, the, closely, related, 'CRK29'])]). relacion([sujeto(['These', data, support, a, model, where, 'Arabidopsis', 'CRKs', are, synthesized, upon, pathogen, 'perception,']), verbo([associate]), complemento([with, the, 'FLS2', 'complex,', and, coordinately, act, to, enhance, plant, immune, responses])]). relacion([sujeto(['Over', the, last, two, 'decades,', an, abundant, literature, on, maternal, effects, in, birds]), verbo([has]), complemento([shown, that, several, of, these, compounds, '(', i])]). relacion([sujeto(['Here,', we]), verbo([report]), complemento([the, results, of, an, interspecific, comparative, analysis, on, 'birds\'', egg, yolk, composition, '(', i])]). relacion([sujeto([androgens, and, 'antioxidants)', where, we]), verbo([found]), complemento([that, yolk, carotenoid, and, vitamin, 'E', concentrations, are, positively, 'associated,', supporting, the, hypothesis, that, these, two, antioxidants, act, in, synergy])]). relacion([sujeto(['The', concentrations, of, vitamin, 'E', also]), verbo([increased]), complemento([with, increasing, concentrations, of, testosterone])]). relacion([sujeto(['MicroRNAs', '(', 'miRNA)', represent, small, regulatory, 'RNA', molecules, that]), verbo([have]), complemento([been, shown, to, act, as, negative, regulators, of, gene, expression, controlling, different, biological, 'processes,', including, 'immune-system', homeostasis, and, function])]). relacion([sujeto(['The', predicted, 'miR-146a\'s']), verbo([target]), complemento([complement, factor, 'H', '(', 'CFH)', mRNA, and, protein, expression, was, also, downregulated, in, 'TLE', rat, model])]). relacion([sujeto(['Downregulating', 'miR-146a', by, intracerebroventricularly, injection, of, 'antagomir-146a']), verbo([enhanced]), complemento([the, hippocampal, expression, of, 'CFH', in, 'TLE', model, and, decreased, seizure, susceptibility])]). relacion([sujeto(['These', findings]), verbo([suggest]), complemento([that, immunopathological, deficits, associated, with, 'TLE', can, in, part, be, explained, by, a, generalized, 'miR-146a-mediated', 'down-regulation', of, 'CFH', that, may, contribute, to, epileptogenesis, in, a, rat, model, of, 'TLE'])]). relacion([sujeto(['Headaches', and, facial, pain]), verbo([have]), complemento([been, identified, as, the, most, prevalent, form, of, pain, among, patients, with, glioblastoma, 'multiforme,', the, most, common, malignant, primary, brain, tumour])]). relacion([sujeto(['Despite', 'this,', minimal, research]), verbo([has]), complemento([been, undertaken, investigating, the, direct, and, indirect, impact, these, headaches, have, on, their, quality, of, life])]). relacion([sujeto(['Therefore,', in, this, 'study,', we, aimed, at]), verbo([gained]), complemento([a, personal, insight, into, the, importance, and, impact, that, these, headaches, have, on, the, quality, of, life, of, patients, with, glioblastoma, multiforme])]). relacion([sujeto(['Interviews', were, 'audio-recorded,']), verbo([transcribed]), complemento([verbatim, and, then, qualitatively, analysed, using, thematic, analysis])]). relacion([sujeto(['Participants']), verbo([recruited]), complemento([from, a, tertiary, referral, hospital, in, 'Birmingham,', 'UK'])]). relacion([sujeto([3, themes, were, 'identified:', '(', 1, ')', an, underlying, attitude, of, determination, and, 'positivity;', '(', 2, ')', impact, of, headache, unpredictability, on, social, 'interaction;', '(', 3, ')', headaches]), verbo([found]), complemento([to, act, as, a, springboard, onto, thoughts, regarding, their, disease, and, future])]). relacion([sujeto(['In', clinical, 'practice,', using, headache, diaries, for, these, patients, may, help]), verbo([provide]), complemento([a, more, comprehensive, assessment, and, further, aid, management, plans])]). relacion([sujeto(['Alongside']), verbo([acting]), complemento([as, an, important, reminder, of, the, potential, secondary, implications, of, this, 'disease,', suggestions, for, future, research, include, quantitatively, investigating, whether, headaches, can, act, as, a, prognostic, indicator, for, quality, of, life, within, this, patient, demographic, and, determining, whether, these, conclusions, also, hold, true, for, a, wider, spectrum, of, patients, with, brain, tumour])]). relacion([sujeto(['Up', to, 18, '%', of, adolescents, will, engage, in, an]), verbo([act]), complemento([of, 'self-harm', before, young, 'adulthood,', with, the, majority, of, acts, occurring, in, private])]). relacion([sujeto(['Mobile', apps, may, offer, a, way, of]), verbo([providing]), complemento([support, for, young, people, at, times, of, distress, to, prevent, 'self-harm'])]). relacion([sujeto(['We', will]), verbo([recruit]), complemento([young, people, '(', 'n=50)', attending, specialist, child, and, adolescent, mental, health, services, with, a, current, or, past, history, of, 'self-harm', to, trial, 'BlueIce', as, an, adjunct, to, their, usual, care])]). relacion([sujeto(['The', recruitment]), verbo([target]), complemento([was, 50, ',', and, by, the, beginning, of, 'November', 54, young, people, had, been, referred])]). relacion([sujeto(['It', will, determine, whether, 'BlueIce', is, 'acceptable,', how, often, it, is, 'used,', and, whether, it, is, safe, and, does, not]), verbo([have]), complemento([any, unintentional, adverse, effects])]). relacion([sujeto(['Behaviourally', spontaneous, confabulation, denotes, a, distinct, syndrome, consisting, of, confabulations, that, patients]), verbo([act]), complemento(['upon,', 'disorientation,', and, amnesia])]). relacion([sujeto(['The', patients]), verbo([act]), complemento([according, to, ideas, and, obligations, that, can, mostly, be, traced, back, to, real, experiences, in, their, 'past,', but, which, are, not, currently, valid, guides, of, thinking, and, behaviour])]). relacion([sujeto(['Failure', of, this, 'function,', which, we, call, orbitofrontal, reality, 'filtering,', is]), verbo([associated]), complemento([with, behaviourally, spontaneous, confabulation, and, disorientation, after, acute, and, focal, brain, 'damage,', but, not, with, other, forms, of, 'confabulation,', and, not, with, reality, confusion, in, degenerative, dementia])]). relacion([sujeto(['Current', endocrine, therapeutics, for, the, 'estrogen-dependent', disease, endometriosis, often]), verbo([lead]), complemento([to, considerable, 'side-effects', as, they, act, by, reducing, estrogen, action, systemically])]). relacion([sujeto(['A', more, recent, approach, takes, advantage, of, the, fact, that, the, weak, estrogen, estrone, '(', 'E1)', which, is, abundant, in, the, 'plasma,', is]), verbo([activated]), complemento([in, the, target, cell, to, the, highly, estrogenic, estradiol, '(', 'E2)', by, 17, 'β-hydroxysteroid', dehydrogenase, type, 1, '(', 17, 'β-HSD1)'])]). relacion([sujeto([17, 'β-HSD1', is, overexpressed, in, endometriosis, and, thus, a, promising]), verbo([target]), complemento([for, the, treatment, of, this, 'disease,', with, the, prospect, of, less, 'target-associated', 'side-effects'])]). relacion([sujeto(['We', describe, the, structural, optimizations]), verbo([leading]), complemento([to, the, discovery, of, '(', 5, -, '(', 3, ',', 5, -, 'dichloro-4-methoxyphenyl)thiophen-2-yl)(2,6-difluoro-3-hydroxyphenyl)methanone', 20, ',', which, displayed, a, 'sub-nanomolar', 'IC50', towards, 17, 'β-HSD1', as, well, as, high, selectivity, over, the, type, 2, 'enzyme,', the, estrogen, receptors, α, and, β, and, a, range, of, hepatic, 'CYP', enzymes])]). relacion([sujeto(['Physical', activity, interventions]), verbo([targeting]), complemento([children, and, adolescents, '(', '≤18 years)', often, focus, on, complex, 'intra-', and, 'inter-personal', behavioral, 'constructs,', 'social-ecological', 'frameworks,', or, some, combination, of, both])]). relacion([sujeto(['Recently', published, 'meta-analytical', reviews, and, 'large-scale', randomized, controlled, trials]), verbo([have]), complemento([demonstrated, that, these, intervention, approaches, have, largely, produced, minimal, or, no, improvements, in, young, 'people\'s', physical, activity, levels])]). relacion([sujeto(['In', this, 'paper,', we, propose, that, the, main, reason, for, previous, 'studies\'', limited, effects, is, that, fundamental, mechanisms, that]), verbo([lead]), complemento([to, change, in, youth, physical, activity, have, often, been, overlooked, or, misunderstood])]). relacion([sujeto(['Evidence', from, observational, and, experimental, studies, is, presented, to, support, the, development, of, a, new, theory, positing, that, the, primary, mechanisms, of, change, in, many, youth, physical, activity, interventions, are, approaches, that, fall, into, one, of, the, following, three, 'categories:', '(', 'a)', the, expansion, of, opportunities, for, youth, to, be, active, by, the, inclusion, of, a, new, occasion, to, be, 'active,', '(', 'b)', the, extension, of, an, existing, physical, activity, opportunity, by]), verbo([increasing]), complemento([the, amount, of, time, allocated, for, that, 'opportunity,', 'and/or', '(', 'c)', the, enhancement, of, existing, physical, activity, opportunities, through, strategies, designed, to, increase, physical, activity, above, routine, practice])]). relacion([sujeto(['The', 'TEO', offers, a, new, way, to, understand, youth, physical, activity, behaviors, and]), verbo([provides]), complemento([a, common, taxonomy, by, which, interventionists, can, identify, appropriate, targets, for, interventions, across, different, settings, and, contexts])]). relacion([sujeto(['We', believe, the, formalization, of, the, 'TEO', concepts, will, propel, them, to, the, forefront, in, the, design, of, future, intervention, studies, and, through, their, 'use,']), verbo([lead]), complemento([to, a, greater, impact, on, youth, activity, behaviors, than, what, has, been, demonstrated, in, previous, studies])]). relacion([sujeto(['NC', patients, did, not]), verbo([have]), complemento([significant, changes])]). relacion([sujeto(['A', similar, pattern, was]), verbo([found]), complemento([regarding, lung, 'function,', use, of, rescue, 'medication,', and, days, free, of, symptoms])]). relacion([sujeto(['After', 2, &, 'nbsp;weeks', of, oral, 'corticosteroids,', an]), verbo([increase]), complemento([occurred, in, those, who, achieved, the, 'ACQ', cut, 'off;', 'however,', 53.8, '%', of, 'C', patients, had, an, 'ACQ', &, 'lt;', 1.57, versus, 21.1, '%', of, 'NC', patients, '(', p, =, 0.03, ')'])]). relacion([sujeto(['Conversely,', application, of, a, 'low-cost,', easy, to, implement, systematic, protocol, can]), verbo([prevent]), complemento([up, to, 25, '%', of, 'SA', patients, from, 'up-titrating', to, new, and, complex, 'therapies,', thus, reducing, costs, and, morbidity])]). relacion([sujeto(['Geographic', variation, in, health, care, use]), verbo([has]), complemento([been, demonstrated, in, many, countries, over, many, years])]). relacion([sujeto(['Despite', the, wealth, of, studies, demonstrating, variation, in, care, 'internationally,', there, is, relatively, little, research, that, explores, the, best, ways, of]), verbo([responding]), complemento([to, unwarranted, variation])]). relacion([sujeto(['Groucho', '(', 'Gro)/Transducin-like', enhancer, of, split, '(', 'TLE)', family, proteins]), verbo([act]), complemento([as, 'co-repressors', of, many, transcription, 'factors,', and, are, involved, in, key, signaling, pathways])]). relacion([sujeto(['TLE1', negatively]), verbo([regulates]), complemento([inflammation, and, has, potential, roles, in, various, 'diseases,', including, cancer])]). relacion([sujeto(['Previous', studies]), verbo([suggest]), complemento(['TLE1', could, be, used, as, a, diagnostic, marker, and, is, a, possible, therapeutic, target, in, various, malignancies])]). relacion([sujeto(['In', this, 'review,', we, highlight, the, functions, of, 'TLE1', in, cancer, and, explore]), verbo([targeted]), complemento([approaches, for, cancer, diagnosis, and, treatment])]). relacion([sujeto(['The', 'UV-vis', absorption, 'spectroscopy,', circular, dichroism, and, molecular, docking, studies]), verbo([suggest]), complemento([that, 1, -, 3, associate, with, telomeric, and, 'c-myc', 'G-quadruplexes', via, groove, 'binding,', and, electrostatic, interactions])]). relacion([sujeto(['On', the, other, 'hand,', 1, -, 3]), verbo([act]), complemento([as, efficient, and, selective, ligand, for, telomeric, quadruplex, 'DNA', under, molecular, crowding, conditions])]). relacion([sujeto(['The', behavior, of, biochemical, reactions]), verbo([requiring]), complemento([repeated, enzymatic, substrate, modification, depends, critically, on, whether, the, enzymes, act, processively, or, distributively])]). relacion([sujeto(['Whereas', processive, enzymes]), verbo([bind]), complemento([only, once, to, a, substrate, before, carrying, out, a, sequence, of, 'modifications,', distributive, enzymes, release, the, substrate, after, each, modification, and, thus, require, repeated, bindings])]). relacion([sujeto(['Recent', experimental, and, computational, studies]), verbo([have]), complemento([revealed, that, distributive, enzymes, can, act, processively, due, to, rapid, rebindings, '(', 'so-called', 'quasi-processivity)'])]). relacion([sujeto(['Importantly,', rebinding]), verbo([requires]), complemento([that, connections, be, added, to, the, 'well-mixed', 'reaction network;', merely, modifying, rate, constants, is, insufficient])]). relacion([sujeto(['We', then, use, these, 'well-mixed', models, to]), verbo([suggest]), complemento([experiments, to, 1, ')', detect, 'quasi-processivity', and, 2, ')', test, the, theory])]). relacion([sujeto(['In', many, 'cases,', the, activity, of, motor, proteins, such, as, nonmuscle, myosins, is]), verbo([required]), complemento([for, appropriate, constriction, of, these, contractile, rings])]). relacion([sujeto(['In', the, gonad, of, the, nematode, worm, 'Caenorhabditis', 'elegans,', ring, channels, are, a, specialized, form, of, contractile, ring, that, are]), verbo([maintained]), complemento([at, a, constant, diameter, before, oogenesis])]). relacion([sujeto(['We', propose, a, model, of, ring, channel, maintenance, that, explicitly, incorporates, force, generation, by, motor, proteins, that, can]), verbo([act]), complemento([normally, or, tangentially, to, the, ring, channel, opening])]). relacion([sujeto(['We']), verbo([find]), complemento([that, both, modes, of, force, generation, are, needed, to, maintain, the, ring, channels])]). relacion([sujeto(['We', demonstrate, experimentally, that, the, type, 'II', myosins, 'NMY-1', and, 'NMY-2', antagonize, each, other, in, the, ring, channels, by, producing, force, in, perpendicular, 'directions:', the, experimental, depletion, of, 'NMY-1/theoretical']), verbo([decrease]), complemento([in, orthogonal, force, allows, premature, ring, constriction, and, 'cellularization,', whereas, the, experimental, depletion, of, 'NMY-2/theoretical', decrease, in, tangential, force, opens, the, ring, channels, and, prevents, cellularization])]). relacion([sujeto(['Together,', our, experimental, and, theoretical, results, show, that, both, 'forces,']), verbo([mediated]), complemento([by, 'NMY-1', and, 'NMY-2,', are, crucial, for, maintaining, the, appropriate, ring, channel, diameter, and, dynamics, throughout, the, gonad])]). relacion([sujeto(['Magainin', 2, '(', 'MAG2)', and, 'PGLa', are, two, 'α-helical', antimicrobial, peptides]), verbo([found]), complemento([in, the, skin, of, the, 'African', frog, 'Xenopus', laevis])]). relacion([sujeto(['They']), verbo([act]), complemento([by, permeabilizing, bacterial, membranes, and, exhibit, an, exemplary, synergism])]). relacion([sujeto(['The', amphiphilic, 'MAG2', helix, was]), verbo([found]), complemento([to, lie, flat, on, the, membrane, surface, in, 1, ',', 2, -, 'dimyristoyl-sn-glycero-3-phosphatidylcholine', '(', 'DMPC)/1,2-dimyristoyl-sn-glycero-3-phosphatidylglycerol', '(', 'DMPG)', and, 1, -, 'palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine', '(', 'POPC)/1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylglycerol', '(', 'POPG),', as, 'expected,', with, a, tilt, angle, close, to, 90, °])]). relacion([sujeto(['Since', this, interaction, was]), verbo([found]), complemento([to, occur, in, a, concentration, range, where, the, peptides, per, se, do, not, interact, with, their, own, 'type,', we, propose, that, 'MAG2', forms, a, stable, heterodimer, with, 'PGLa'])]). relacion([sujeto(['We', thus]), verbo([suggest]), complemento([that, the, two, negative, charges, on, the, 'C-terminus', of, the, obliquely, tilted, 'MAG2', peptides, neutralize, some, of, the, cationic, groups, on, the, upright, 'PGLa', helices])]). relacion([sujeto(['Across', the, entire, distribution, of, a, 'species,', populations, may]), verbo([have]), complemento([variable, responses, to, environmental, perturbations])]). relacion([sujeto(['In', some, 'areas,', warm, temperatures, may, allow, bats, to, remain, active, through, 'winter,', thus]), verbo([decreasing]), complemento([their, susceptibility, to, 'WNS', 'and/or', mortality, associated, with, migration, to, wintering, grounds])]). relacion([sujeto(['These', areas, could]), verbo([act]), complemento([as, a, refugia, and, be, important, for, the, persistence, of, local, populations])]). relacion([sujeto(['We']), verbo([found]), complemento([high, bat, species, richness, on, the, 'Coastal', 'Plain', in, 'winter,', with, 'winter-active', species, including, those, known, to, hibernate, throughout, most, of, their, range, and, others, known, to, be, long, distance, migrants])]). relacion([sujeto(['In', the, 'Coastal', 'Plain,', the, long, distance, migratory, hoary, bat, '(', 'Lasiurus', 'cinereus)', was, active, in, the, winter, but, not, present, during, the, other, 'seasons,', and, the, long, distance, migratory, 'silver-haired', bat, '(', 'Lasionycteris', 'noctivagans)', was, active, primarily, in, the, 'winter,']), verbo([suggesting]), complemento([the, 'Coastal', 'Plain', may, be, an, overwintering, ground, for, these, two, species])]). relacion([sujeto(['We']), verbo([suggest]), complemento([that, the, winter, activity, exhibited, by, populations, of, bats, on, the, 'North', 'Carolina', 'Coastal', 'Plain', has, important, conservation, implications, and, these, populations, should, be, carefully, monitored, and, afforded, protection])]). relacion([sujeto(['Previous', research]), verbo([has]), complemento([attempted, to, determine, whether, ingroup, favoritism, is, produced, by, categorization, or, intragroup, interdependencies, '(', reciprocation, 'expectations),', but, recent, literature, suggests, that, it, is, not, possible, to, tease, these, influences, apart])]). relacion([sujeto(['We']), verbo([report]), complemento([two, studies, that, investigate, how, ingroup, favoritism, evolves, over, time, in, social, interaction])]). relacion([sujeto(['The', levels, of, ingroup, favoritism, were, affected, by, categorization, and, 'inequality,', and, the, level, of, ingroup, favoritism, changed, over, 'time,']), verbo([increasing]), complemento([or, decreasing, depending, on, the, nature, of, the, initial, intergroup, structure])]). relacion([sujeto(['We', conclude, by]), verbo([providing]), complemento([two, explanations, for, this, 'change:', emergent, 'norms,', and, changes, to, the, intergroup, situation, produced, by, interaction])]). relacion([sujeto(['Our', experiments, confirm, the, value, of, studying, the, evolution, of, minimal, group, 'behavior,', especially, for, explaining, why, low, status, groups]), verbo([act]), complemento([to, preserve, intergroup, inequalities])]). relacion([sujeto(['Being', sensitive, to, the, values, of, service, users, and, their, caregivers, may, allow, service, providers, to, better]), verbo([act]), complemento([on, points, that, may, bring, about, change, in, 'non-compliant', service, users, with, schizophrenia, and, metabolic, comorbidities])]). relacion([sujeto(['Cicada', songs]), verbo([act]), complemento([as, 'species-specific', premating, barriers, and, have, been, used, extensively, to, reveal, hidden, taxonomic, diversity, in, morphologically, similar, species])]). relacion([sujeto(['The', 'Palaearctic', 'Cicadetta', montana, species, complex, is, an, excellent, example, where, distinct, song, patterns]), verbo([have]), complemento([disclosed, multiple, recently, described, species])]). relacion([sujeto(['Based', on, 'acoustic,', 'morphological,', 'molecular,', ecological, and, spatial, data, sampled, throughout, their, broad, 'European', 'distribution,', we]), verbo([find]), complemento([that, 'Cicadetta', brevipennis, s])]). relacion([sujeto(['The', fifth, lineage]), verbo([requires]), complemento([additional, investigation])]). relacion([sujeto([brevipennis, song, groups, exhibit, 'characteristic,', clearly, distinct, basic, song, patterns, that]), verbo([act]), complemento([as, reproductive, barriers])]). relacion([sujeto(['In', our, favoured, scenario, the, phylogenetic, pairs, originated, in, common, 'Pleistocene', glacial, refuges, where, the, taxa, speciated, and, experienced, sporadic, 'inter-group', hybridization]), verbo([leading]), complemento([to, extensive, introgression, and, mitochondrial, capture])]). relacion([sujeto(['Highly']), verbo([conserved]), complemento(['MutS', '(', 'MSH)', and, 'MutL', '(', 'MLH/PMS)', homologues, initiate, mismatch, repair, 'and,', in, higher, 'eukaryotes,', act, as, 'DNA', damage, sensors, that, can, trigger, apoptosis])]). relacion([sujeto(['Defects', in, human, mismatch, repair, genes]), verbo([cause]), complemento(['Lynch', syndrome, or, hereditary, 'non-polyposis', colorectal, cancer, and, 10, -, 40, '%', of, related, sporadic, tumours])]). relacion([sujeto(['However,', the, collaborative, mechanics, of, 'MSH', and, 'MLH/PMS', proteins]), verbo([have]), complemento([not, been, resolved, in, any, organism])]). relacion([sujeto(['The', 'EcMutS', sliding, clamps]), verbo([act]), complemento([as, a, platform, to, recruit, 'EcMutL', onto, the, mismatched, 'DNA,', forming, an, 'EcMutS-EcMutL', search, complex, that, then, closely, follows, the, 'DNA', backbone])]). relacion([sujeto(['ATP']), verbo([binding]), complemento([by, 'EcMutL', establishes, a, second, 'long-lived', 'DNA', clamp, that, oscillates, between, the, principal, 'EcMutS-EcMutL', search, complex, and, unrestricted, 'EcMutS', and, 'EcMutL', sliding, clamps])]). relacion([sujeto(['The', 'EcMutH', endonuclease, that]), verbo([targets]), complemento([mismatch, repair, excision, only, binds, clamped, 'EcMutL,', increasing, its, 'DNA', association, kinetics, by, more, than, 1, ',', 0, -, fold])]). relacion([sujeto(['The', assembly, of, an, 'EcMutS-EcMutL-EcMutH', search, complex, illustrates, how, sequential, stable, sliding, clamps, can]), verbo([modulate]), complemento(['one-dimensional', diffusion, mechanics, along, the, 'DNA', to, direct, mismatch, repair])]). relacion([sujeto(['Here', we, test, the, hypothesis, that, 'RNA', modification, enzymes, also]), verbo([act]), complemento([as, 'RNA', chaperones])]). relacion([sujeto(['Using', 'TruB', as, a, 'model,', we, demonstrate, that, 'TruB', folds, tRNA, independent, of, its, catalytic, 'activity,', thus]), verbo([increasing]), complemento([the, fraction, of, tRNA, that, can, be, aminoacylated])]). relacion([sujeto(['By', rapid, kinetic, 'stopped-flow', 'analysis,', we, identified, the, molecular, mechanism, of, 'TruB\'s', 'RNA', chaperone, 'activity:', 'TruB']), verbo([binds]), complemento([and, unfolds, both, misfolded, and, folded, tRNAs, thereby, providing, misfolded, tRNAs, a, second, chance, at, folding])]). relacion([sujeto(['Previously,', it]), verbo([has]), complemento([been, shown, that, a, catalytically, inactive, 'TruB', variant, has, no, phenotype, when, expressed, in, an, 'Escherichia', coli, truB, 'KO', strain, '[', 'Gutgsell', 'N,', et, al])]). relacion([sujeto([coli, strains]), verbo([expressing]), complemento([a, 'TruB', variant, impaired, in, tRNA, binding, and, in, in, vitro, tRNA, folding, cannot, compete, with, 'WT', 'E'])]). relacion([sujeto(['In', 'conclusion,', we, prove, the, tRNA, chaperone, activity, of, the, pseudouridine, synthase, 'TruB,']), verbo([reveal]), complemento([its, molecular, 'mechanism,', and, demonstrate, its, importance, for, cellular, fitness])]). relacion([sujeto(['The', 'EACE', also, was, tasked, with, conducting, clinically, relevant, 'research,', fostering, 'collaborations,', and, building, partnerships, across, multidisciplinary, 'international,', 'federal,', and, academic, networks, to, optimize, the, quality, of, life, of, service, members, and, veterans, who]), verbo([have]), complemento([sustained, extremity, trauma, or, amputations])]). relacion([sujeto(['The', 'EACE', researchers]), verbo([have]), complemento([efforts, in, four, key, research, focus, areas, relevant, to, extremity, trauma, and, 'amputation:', '(', 1, ')', 'Novel', 'Rehabilitation', 'Interventions,', '(', 2, ')', 'Advanced', 'Prosthetic', and, 'Orthotic', 'Technologies,', '(', 3, ')', 'Epidemiology', and, 'Surveillance,', and, '(', 4, ')', 'Medical', and, 'Surgical', 'Innovations'])]). relacion([sujeto(['This', overview, describes, the, 'EACE', efforts, to, 'innovate,', 'discover,', and]), verbo([translate]), complemento([knowledge, gleaned, from, collaborative, research, partnerships, into, clinical, practice, and, policy])]). relacion([sujeto(['Corneal', endothelial, cells]), verbo([have]), complemento([a, low, proliferative, 'capacity,', so, preserving, their, barrier, function, under, suboptimal, conditions, that, cause, osmotic, 'imbalance,', such, as, those, arising, from, corneal, 'pathologies,', 'age,', 'cryopreservation,', and, 'transplantation,', is, essential, for, maintaining, corneal, transparency])]). relacion([sujeto(['We']), verbo([have]), complemento([investigated, the, signaling, induced, by, hyperosmotic, shock, that, reversibly, disrupts, corneal, endothelial, barriers, in, human, endothelial, cells, and, in, murine, corneas])]). relacion([sujeto(['Endothelial', barrier, properties, were, analyzed, in, vitro, by, electric, cell, substrate, impedance, sensing, '(', 'ECIS)', and, confocal, microscopy, of, the, human, endothelial, cell, line, 'B4G12-HCEC,', 'and,', ex, 'vivo,', by, confocal, microscopy, and]), verbo([stimulated]), complemento(['emission-depletion', '(', 'STED)', 'super-resolution', microscopy, of, murine, corneas])]). relacion([sujeto(['Cell', signaling, in, response, to, hyperosmotic, 'stress,']), verbo([induced]), complemento([with, an, excess, of, sodium, 'chloride,', was, investigated, in, 'B4G12-HCECs'])]). relacion([sujeto(['Rho', 'GTPase', activity, was, detected, by, pulldown, assays, with, recombinant, 'GST', proteins, fused, to, the, 'Rho']), verbo([binding]), complemento([domains, of, 'Rho', effectors])]). relacion([sujeto(['Hyperosmotic', stress]), verbo([increased]), complemento([actin, polymerization, and, activated, the, 'Rho', 'GTPases', 'Rac1', and, 'RhoA,', but, not, 'Cdc42'])]). relacion([sujeto(['In', 'contrast,', 'Rac1', and, 'RhoA', activation]), verbo([enhanced]), complemento([constitutive, endothelial, barrier, function, and, accelerated, barrier, repair])]). relacion([sujeto(['Our', results, indicate, that, 'Rac1', and, 'RhoA', activation, do, not]), verbo([mediate]), complemento(['stress-induced', cell, contraction, but, are, endothelial, responses, that, act, to, restore, and, maintain, barrier, homeostasis])]). relacion([sujeto(['This', is, a, longitudinal, 'study,', including, one, deaf, 'individual,', called, 'N,']), verbo([interacting]), complemento([with, his, family, and, speech, therapists])]). relacion([sujeto(['During', the, therapeutic, process, developed, inside, the, bilingual, dialogical, 'clinic,', 'N']), verbo([participated]), complemento([in, interactive, contexts, and, could, constitute, himself, as, author, of, his, sign, language, texts])]). relacion([sujeto(['In', 'addition,']), verbo([he]), complemento([started, to, act, dialogically, and, use, verbal, and, nonverbal, signs])]). relacion([sujeto(['More', women, than, men]), verbo([reported]), complemento([they, felt, that, their, communication, had, worsened, throughout, their, careers])]). relacion([sujeto(['All', the, women]), verbo([reported]), complemento([they, experienced, insecurity, when, speaking, in, public])]). relacion([sujeto(['Bordetella', pertussis, is, a, human, pathogen, that, can, infect, the, respiratory, tract, and]), verbo([cause]), complemento([the, disease, known, as, whooping, cough])]). relacion([sujeto([pertussis, uses, pertussis, toxin, '(', 'PT)', and, adenylate, cyclase, toxin, '(', 'ACT)', to, kill, and]), verbo([modulate]), complemento([host, cells, to, allow, the, pathogen, to, survive, and, persist])]). relacion([sujeto(['RpoE', is, a, sigma, factor, which, in, other, 'bacteria,']), verbo([responds]), complemento([to, 'oxidative,', 'heat,', and, other, environmental, stresses])]). relacion([sujeto(['RseA', is, a, negative, regulator, of, 'RpoE', that, sequesters, the, sigma, factor, to]), verbo([regulate]), complemento([gene, expression, based, on, conditions])]). relacion([sujeto(['RNAseq', analysis, was, performed, and, 263, genes, were, differentially]), verbo([regulated]), complemento([by, 'RpoE', and, surprisingly, the, rseA, mutant, strain, where, 'RpoE', activity, was, 'elevated,', expressed, very, little, pertussis, toxin])]). relacion([sujeto(['Our', data]), verbo([suggest]), complemento([that, 'RpoE', can, modulate, 'PT', and, 'ACT', expression, indirectly, 'through,', unidentified, 'mechanisms,', in, response, to, conditions])]). relacion([sujeto(['Electronic', devices, made, from, organic, materials]), verbo([have]), complemento([the, potential, to, support, a, more, ecologically, friendly, and, affordable, future])]). relacion([sujeto(['Until', now, the, 3, -, dimensional, profiling, of, oxygen, species, in, organic, semiconductors]), verbo([has]), complemento([been, elusive, and, the, effect, of, oxygen, remains, disputed])]). relacion([sujeto(['Channels', of, diffused, oxygen, are]), verbo([found]), complemento([extending, from, uniform, oxygen, inclusion, layers, at, the, surface])]). relacion([sujeto(['These', channels, extend, to, depths, in, excess, of, 1.8, μm, and]), verbo([act]), complemento([as, an, entry, point, for, oxygen, to, diffuse, along, the, 'ab-plane', of, the, crystal, with, at, least, some, of, the, diffused, oxygen, molecularly, binding, to, rubrene])]). relacion([sujeto(['Our', investigation, of, surfaces, at, different, stages, of, evolution]), verbo([reveals]), complemento([the, extent, of, oxygen, 'inclusion,', which, affects, 'rubrene\'s', optical, and, transport, 'properties,', and, is, consequently, of, importance, for, the, reliability, and, longevity, of, devices])]). relacion([sujeto(['Engulfment', and, cell, motility, 1, '(', 'ELMO1)', functions, as, a, guanine, exchange, factor, for, 'Rac1', and, was, recently]), verbo([found]), complemento([to, protect, endothelial, cells, from, apoptosis])]). relacion([sujeto(['Genome', wide, association, studies]), verbo([suggest]), complemento([that, polymorphisms, within, human, elmo1, act, as, a, potential, contributing, factor, for, the, development, of, diabetic, nephropathy])]). relacion([sujeto(['However,', hyperglycaemia]), verbo([leads]), complemento([to, pathophysiological, and, functional, alterations, within, the, 'pronephros,', which, could, be, rescued, via, 'ELMO1', overexpression])]). relacion([sujeto(['Zebrafish', 'ELMO1', crispants, exhibited, a, renal, pathophysiology, due, to]), verbo([increased]), complemento([apoptosis, which, could, be, rescued, by, the, inhibition, of, apoptosis])]). relacion([sujeto(['However,', 'ELMO1', was, not, specifically, or, distinctly]), verbo([regulated]), complemento([under, either, one, of, the, disease, conditions])]). relacion([sujeto(['Collectively,', these, results, highlight, 'ELMO1', as, an, important, factor, for, glomerular, protection, and, renal, cell, survival, via]), verbo([decreasing]), complemento(['apoptosis,', especially, under, diabetic, conditions])]). relacion([sujeto(['Receptor', protein, tyrosine, phosphatase, σ, '(', 'PTPσ)', and, its, subfamily, member, 'LAR']), verbo([act]), complemento([as, transmembrane, receptors, that, mediate, growth, inhibition, of, chondroitin, sulfate, proteoglycans, '(', 'CSPGs)'])]). relacion([sujeto(['Inhibition', of, either, receptor]), verbo([increases]), complemento([axon, growth, into, and, beyond, scar, tissues, after, 'CNS', injury])]). relacion([sujeto(['However,', it, is, unclear, why, neurons]), verbo([express]), complemento([two, similar, 'CSPG', 'receptors,', nor, whether, they, use, the, same, or, different, intracellular, pathways])]). relacion([sujeto(['We']), verbo([have]), complemento([now, studied, the, signaling, pathways, of, these, two, receptors, using, 'N2A', cells, and, primary, neurons, derived, from, knockout, mice])]). relacion([sujeto(['We', demonstrate, that, both, receptors, share, certain, signaling, pathways, '(', 'RhoA,', 'Akt', and, 'Erk),', but, also, use, distinct, signals, to]), verbo([mediate]), complemento(['CSPG', actions])]). relacion([sujeto(['Our', findings, elucidate, the, novel, downstream, pathways, of, 'CSPGs', and]), verbo([suggest]), complemento([potential, synergy, of, blocking, their, two, 'PTP', receptors])]). relacion([sujeto(['Genetic', defects, in, various, red, blood, cell, '(', 'RBC)', cytoskeletal, proteins]), verbo([have]), complemento([been, long, associated, with, changes, in, susceptibility, towards, malaria, infection])]). relacion([sujeto(['In', 'particular,', while, ankyrin, '(', 'Ank-1)', mutations, account, for, approximately, 50, '%', of, hereditary, spherocytosis, '(', 'HS)', 'cases,', an, association, with, malaria, is, not, 'well-established,', and, conflicting, evidence]), verbo([has]), complemento([been, reported])]). relacion([sujeto(['Ank-1((MRI61689/+))', mice, exhibit, an, 'HS-like', phenotype, including, reduction, in, mean, corpuscular, volume, '(', 'MCV),']), verbo([increased]), complemento([osmotic, fragility, and, reduced, 'RBC', deformability])]). relacion([sujeto(['They', were, also]), verbo([found]), complemento([to, be, resistant, to, rodent, malaria, 'Plasmodium', chabaudi, infection])]). relacion([sujeto(['This']), verbo([increased]), complemento([clearance, is, a, novel, resistance, mechanism, which, was, not, observed, in, previous, ankyrin, mouse, models])]). relacion([sujeto(['This', paper, highlights, the, complex, roles, ankyrin, plays, in]), verbo([mediating]), complemento([malaria, resistance])]). relacion([sujeto(['The', computational, repertoire, of, neurons, is]), verbo([enhanced]), complemento([by, regenerative, electrical, signals, initiated, in, dendrites])]). relacion([sujeto(['These', 'events,', referred, to, as, dendritic, 'spikes,', can]), verbo([act]), complemento([as, 'cell-intrinsic', amplifiers, of, synaptic, input])]). relacion([sujeto(['Because', it, is, not, possible, to, block, 'NMDA', spikes, pharmacologically, while]), verbo([maintaining]), complemento(['NMDA', receptors, available, to, initiate, synaptic, 'plasticity,', it, remains, unclear, whether, 'NMDA', spikes, alone, can, trigger, 'LTP'])]). relacion([sujeto(['Decreasing', the, probability, of, 'NMDA', spikes, reduces, 'LTP,', whereas]), verbo([increasing]), complemento([their, probability, enhances, 'LTP'])]). relacion([sujeto(['However,', action, potentials, can, facilitate, 'LTP', induction, by]), verbo([promoting]), complemento(['NMDA', spikes])]). relacion([sujeto(['Thus,', 'NMDA', spikes, are, necessary, and, sufficient, to, produce, the, critical, postsynaptic, depolarization]), verbo([required]), complemento([for, associative, 'LTP', in, 'CA3', pyramidal, cells])]). relacion([sujeto(['A', fundamental, function, of, the, intestinal, epithelium, is, to]), verbo([act]), complemento([as, a, barrier, that, limits, interactions, between, luminal, contents, such, as, the, intestinal, 'microbiota,', the, underlying, immune, system, and, the, remainder, of, the, 'body,', while, supporting, vectorial, transport, of, 'nutrients,', water, and, waste, products])]). relacion([sujeto(['Epithelial', barrier, function]), verbo([requires]), complemento([a, contiguous, layer, of, cells, as, well, as, the, junctions, that, seal, the, paracellular, space, between, epithelial, cells])]). relacion([sujeto(['Compromised', intestinal, barrier, function]), verbo([has]), complemento([been, associated, with, a, number, of, disease, 'states,', both, intestinal, and, systemic])]). relacion([sujeto(['Unfortunately,', most, current, clinical, data, are, 'correlative,', making, it, difficult, to, separate]), verbo([cause]), complemento([from, effect, in, interpreting, the, importance, of, barrier, loss])]). relacion([sujeto(['Some', data, from, experimental, animal, models]), verbo([suggest]), complemento([that, compromised, epithelial, integrity, might, have, a, pathogenic, role, in, specific, gastrointestinal, 'diseases,', but, no, 'FDA-approved', agents, that, target, the, epithelial, barrier, are, presently, available])]). relacion([sujeto(['Here,', we, review, and, discuss, mechanisms, of, intestinal, barrier]), verbo([loss]), complemento([and, the, role, of, intestinal, epithelial, barrier, function, in, pathogenesis, of, both, intestinal, and, systemic, diseases])]). relacion([sujeto(['Most', 'HIV', transmissions, among, men, who]), verbo([have]), complemento([sex, with, men, '(', 'MSM),', the, group, that, accounted, for, 67, '%', of, new, 'US', infections, in, 2014, ',', occur, via, exposure, to, the, rectal, mucosa])]). relacion([sujeto(['However,', it, is, unclear, how, the]), verbo([act]), complemento([of, condomless, receptive, anal, intercourse, '(', 'CRAI)', may, alter, the, mucosal, immune, environment, in, 'HIV-negative', 'MSM'])]). relacion([sujeto(['Our', results, show, that, compared, with, men, who, had, never, engaged, in, anal, 'intercourse,', the, rectal, mucosa, of, 'MSM', engaging, in, 'CRAI']), verbo([has]), complemento([a, distinct, phenotype, characterized, by, higher, levels, of, 'Th17', 'cells,', greater, 'CD8+', 'T', cell, proliferation, and, production, of, 'pro-inflammatory', 'cytokines,', molecular, signatures, associated, with, mucosal, injury, and, repair, likely, mediated, by, innate, immune, 'cells,', and, a, microbiota, enriched, for, the, 'Prevotellaceae', family])]). relacion([sujeto(['These', data]), verbo([provide]), complemento([a, 'high-resolution', model, of, the, 'immunological,', 'molecular,', and, microbiological, perturbations, induced, by, 'CRAI,', will, have, direct, utility, in, understanding, rectal, 'HIV', transmission, among, 'MSM,', and, will, enhance, the, design, of, future, biomedical, prevention, 'interventions,', including, candidate, 'HIV', vaccines])]). relacion([sujeto(['It', is]), verbo([caused]), complemento([by, a, quantitative, or, qualitative, abnormality, of, the, von, 'Willebrand', factor, '(', 'VWF)'])]). relacion([sujeto(['The', analytical, validation, of, 'VWF:Ag,', 'VWF:Act,', 'vWF:CB', is]), verbo([reported]), complemento([in, this, work, and, demonstrates, good, test, performance, of, all, three, 'assays,', with, a, coefficient, of, variation, lower, than, 10, '%', for, both, the, repeatability, and, 'reproducibility,', stability, with, a, deviation, of, less, than, 5, '%', from, the, target, value, after, six, hours, at, room, temperature])]). relacion([sujeto(['Many', of, the, lncRNA]), verbo([have]), complemento([its, own, 'promoter,', and, are, well, conserved, in, mammals])]). relacion([sujeto(['Accumulating', evidence, indicates, that, lncRNAs]), verbo([act]), complemento([as, molecular, switches, in, cellular, 'differentiation,', 'movement,', 'apoptosis,', and, in, the, reprogramming, of, cell, states, by, altering, gene, expression, patterns])]). relacion([sujeto(['Dysregulation', of, transcription, during, this, process, may]), verbo([lead]), complemento([to, several, diseases, including, various, cancers])]). relacion([sujeto(['In', support, of, 'this,', lncRNA, microvascular, invasion, in, hepatocellular, carcinoma, '(', 'MVIH)']), verbo([has]), complemento([been, shown, to, activate, angiogenesis])]). relacion([sujeto(['Furthermore,', 'lncRNA-Meg3-knockout', mouse, showed]), verbo([increased]), complemento([expression, of, vascular, endothelial, growth, factor, pathway, genes, and, increased, cortical, microvessel, density])]). relacion([sujeto(['Overall,', there, is, strong, evidence, that, lncRNA, is, an, important, class, of, regulatory, 'molecule,', and, a, number, of, studies]), verbo([have]), complemento([demonstrated, that, these, can, be, targeted, to, change, cellular, physiology, and, functions])]). relacion([sujeto(['In', this, 'review,', we]), verbo([have]), complemento([attempted, to, summarize, these, studies, and, elucidate, the, potential, of, this, novel, regulatory, molecule, as, a, therapeutic, target])]). relacion([sujeto(['This', is, the, first, assessment, of, the, 'Republic', of, 'Slovenia\'s', efforts, to, synthesize, and]), verbo([report]), complemento([physical, activity, '(', 'PA)', standards, for, children, and, youth, following, the, 'Active', 'Healthy', 'Kids', 'Global', 'Alliance', grading, system, model])]). relacion([sujeto(['The', 'Republic', of, 'Slovenia', 'Report', 'Card', relies, on, research, findings, published, in, 'peer-reviewed', 'journals,', data, compiled, from, national, 'databases,', and, government, initiatives, which]), verbo([have]), complemento([been, monitoring, physical, fitness, standards, in, schools, for, the, past, 34, years, '(', 'SLOfit', and, 'ACDSi)'])]). relacion([sujeto(['The', 'Report', 'Card', initiative]), verbo([has]), complemento([been, jointly, coordinated, by, the, 'University', of, 'Primorska', and, the, 'University', of, 'Ljubljana'])]). relacion([sujeto(['This', inclusive, 'PA']), verbo([report]), complemento([indicates, that, overall, physical, activity, minutes, remain, high, in, 'Slovenian', children, and, 'youth;', 'however,', more, research, is, needed, to, determine, the, effects, of, family, 'life,', peer, 'influences,', and, the, built, environment, on, active, play, behaviors])]). relacion([sujeto(['The', 2016, 'Indian', 'Report', 'Card', on, 'Physical', 'Activity', for, 'Children', and, 'Youth']), verbo([has]), complemento([been, conceptualized, to, highlight, this, epidemic, by, appraising, 'behaviors,', 'contexts,', 'strategies,', and, investments, related, to, physical, activity, of, 'Indian', children, and, youth])]). relacion([sujeto(['The']), verbo([report]), complemento([card, identifies, gaps, in, both, investments, and, research, that, need, to, be, addressed, before, understanding, the, complete, picture, of, active, living, in, children, and, youth, in, 'India'])]). relacion([sujeto(['This']), verbo([report]), complemento([card, '(', 'RC)', is, intended, to, increase, awareness, and, sensitivity, about, issues, surrounding, 'PA', and, 'SB', in, 'Ghana'])]). relacion([sujeto(['A', conscious, national, investment, effort, can]), verbo([increase]), complemento([overall, 'PA', among, children])]). relacion([sujeto(['The', 'Japan']), verbo([report]), complemento([card, followed, the, methodology, of, the, 'Canadian', and, 'Scottish', report, 'cards,', but, was, adapted, to, reflect, the, 'Japanese', context])]). relacion([sujeto(['The', 'Japan']), verbo([report]), complemento([card, illustrated, some, favorable, health, 'behaviors,', health, 'outcomes,', and, influences])]). relacion([sujeto(['It']), verbo([provides]), complemento([a, compilation, of, existing, information, throughout, the, country, and, assesses, how, well, it, is, doing, at, promoting, opportunities, for, children, and, youth])]). relacion([sujeto(['Some', indicators]), verbo([report]), complemento([incomplete, information, or, a, lack, of, data])]). relacion([sujeto([63, '%', of, children, and, youth]), verbo([have]), complemento([low, physical, activity, levels])]). relacion([sujeto(['Unlike', 2014, '\'', s]), verbo([report]), complemento(['card,', different, grades, for, the, 'Republic', '(', 'C-)', and, 'Northern', 'Ireland', '(', 'C+)', were, assigned, for, 'Organized', 'Sport', 'Participation'])]). relacion([sujeto(['Although', the, grade, for, 'Overall', 'PA', levels]), verbo([increased]), complemento([to, a, 'D,', this, may, reflect, the, increased, quality, and, quantity, of, data, available])]). relacion([sujeto(['The', double, burden, of, low, 'PA', and, high, sedentary, levels, are, concerning, and, underscore, the, need, for, advocacy, 'toward,', and, surveillance, 'of,', progress, in, achieving]), verbo([targets]), complemento([set, by, the, new, 'National', 'Physical', 'Activity', 'Plan', in, the, 'Republic', and, obesity, and, sport, plans, in, the, 'North'])]). relacion([sujeto(['The', 'Active', 'Healthy', 'Kids', 2016, 'United', 'Arab', 'Emirates', '(', 'UAE)', 'Report', 'Card']), verbo([provides]), complemento([a, systematic, evaluation, of, how, the, 'UAE', is, performing, in, supporting, and, engaging, physical, activity, '(', 'PA)', in, children, and, adolescents])]). relacion([sujeto(['The', 'UAE', leadership]), verbo([has]), complemento([invested, significant, resources, into, improving, 'PA', through, 'school-', and, 'community-based', 'PA', 'interventions;', 'however,', 'inter-', and, intraemirate, 'population-based', strategies, remain, fragmented])]). relacion([sujeto(['Kenya\'s', 2016]), verbo([report]), complemento([card, aimed, to, highlight, the, health, and, 'well-being', of, 'Kenyan', children, and, youth, using, the, best, available, evidence, on, the, physical, activity, of, 'Kenyan', children, and, youth])]). relacion([sujeto(['The']), verbo([report]), complemento([pointed, at, areas, where, 'Kenya', was, succeeding, and, areas, where, more, action, is, required])]). relacion([sujeto(['Although', majority, of, the, children, and, youth]), verbo([have]), complemento([normal, body, 'weight,', there, is, need, to, ensure, that, they, meet, and, maintain, the, physical, activity, levels, recommended, by, the, 'World', 'Health', 'Organization'])]). relacion([sujeto(['More', needs, to, be, done, especially, in, relation, to, the, governmental, and, nongovernmental, 'organizations,', organized, sports, 'participation,', as, well, as, involvement, of, family, and, peers, in]), verbo([promoting]), complemento([healthy, active, lifestyles, among, 'Kenyan', children, and, youth])]). relacion([sujeto(['More', representative, data, for, all, indicators, are]), verbo([required]), complemento([in, 'Kenya'])]). relacion([sujeto(['The', 2016, 'Chilean', 'Report', 'Card', on, 'Physical', 'Activity', for, 'Children', and, 'Youth', is, a, review, of, the, evidence, across, indicators, of, 'behaviors,', 'settings,', and, sources, of, influence]), verbo([associated]), complemento([with, physical, activity, '(', 'PA)', of, 'Chilean', children, and, youth])]). relacion([sujeto(['Grades', assigned, were, for, 'i)', '\'', 'Behaviors', that, contribute, to, overall, 'PA', 'levels\':', 'Overall', 'PA,', 'F;', 'Organized', 'Sport', 'Participation,', 'D;', 'Active', 'Play,', 'INC;', and, 'Active', 'Transportation,', 'C-;', 'ii)', '\'', 'Factors']), verbo([associated]), complemento([with, cardiometabolic, 'risk\':', 'Sedentary', 'Behavior,', 'D;', 'Overweight', and, 'Obesity,', 'F;', 'Fitness,', 'F;', and, 'iii)', '\'', 'Factors', that, influence, 'PA\':', 'Family', and, 'Peers,', 'D;', 'School,', 'D;', 'Community', and, 'Built', 'Environment,', 'C;', 'Government', 'Strategies', and, 'Investments,', 'C'])]). relacion([sujeto(['There', were, clear, research, and, information, gaps, that, need, to, be, filled, with, the, implementation, of, consistent, and]), verbo([regular]), complemento([data, collection, methods])]). relacion([sujeto(['The']), verbo([report]), complemento([card, is, important, for, future, physical, activity, 'advocacy,', 'policy,', and, program, development])]). relacion([sujeto(['The', methodology, used, in, 'Scotland\'s']), verbo([report]), complemento([card, was, adapted, for, 'Qatar'])]). relacion([sujeto(['The', grades]), verbo([have]), complemento([not, improved, since, the, 2014, 'Report', 'Card', and, several, gaps, in, the, literature, are, still, present])]). relacion([sujeto(['While', 'children\'s', physical, activity, levels, remain, low, alongside, competing, sedentary, 'choices,', further, national, plans, and, investment, with, local, actions, are, urgently, needed, to]), verbo([promote]), complemento([physical, activity, especially, via, active, 'play,', active, 'transport,', and, family, support])]). relacion([sujeto(['Countries', that]), verbo([lead]), complemento([in, certain, indicators, often, lag, in, others])]). relacion([sujeto(['The', paradox, of, higher, physical, activity, and, lower, sedentary, behavior, in, countries]), verbo([reporting]), complemento([poorer, 'infrastructure,', and, lower, physical, activity, and, higher, sedentary, behavior, in, countries, reporting, better, 'infrastructure,', suggests, that, autonomy, to, 'play,', 'travel,', or, chore, requirements, 'and/or', fewer, attractive, sedentary, 'pursuits,', rather, than, infrastructure, and, structured, 'activities,', may, facilitate, higher, levels, of, physical, activity])]). relacion([sujeto(['Finland\'s', 2016, 'Report', 'Card', on, 'Physical', 'Activity', for, 'Children', and, 'Youth', gathers, and]), verbo([translates]), complemento([research, results, and, assesses, the, status, and, promotion, of, physical, activity, '(', 'PA)', among, 'Finnish', children, and, youth, less, than, 18, years, of, age])]). relacion([sujeto(['This', article, summarizes, the, results, and]), verbo([provides]), complemento([grades, for, 9, indicators])]). relacion([sujeto(['Despite', good, policies, and, programs, to]), verbo([promote]), complemento(['PA', in, 'Finland,', children, and, youth, overall, 'PA', levels, are, 'low,', whereas, their, time, spent, sedentary, is, high])]). relacion([sujeto(['The', 'Active', 'Healthy', 'Kids', the, 'Netherlands', '(', 'AHKN)', 'Report', 'Card', consolidates, and]), verbo([translates]), complemento([research, and, assesses, how, the, 'Netherlands', is, being, responsible, in, providing, physical, activity, '(', 'PA)', opportunities, for, children, and, youth, '(', &, 'lt;18', 'years)'])]). relacion([sujeto(['Nine', indicators, were, graded, using, the, 'Active', 'Healthy', 'Kids', 'Global', 'Alliance']), verbo([report]), complemento([card, development, 'process,', which, includes, a, synthesis, of, the, best, available, 'research,', 'surveillance,', policy, and, practice, 'findings,', and, expert, consensus])]). relacion([sujeto(['Several', modifiable, factors, of, influence, might, be]), verbo([enhanced]), complemento([to, improve, these, indicators, or, at, least, prevent, regression])]). relacion([sujeto(['Very', few, studies]), verbo([have]), complemento([comprehensively, analyzed, the, physical, activity, of, children, and, adolescents, in, 'Brazil'])]). relacion([sujeto(['The', data, available, were, collected, independently, and, then, synthesized, by, the, 'Research', 'Work', 'Group', using, the, grade, system, developed, for, the, 'First', 'Global', 'Matrix']), verbo([released]), complemento([in, 2014, ',', which, included, 9, indicators, of, physical, activity])]). relacion([sujeto(['Physical', activity, '(', 'PA)', is]), verbo([recognized]), complemento([as, one, of, the, core, modifiable, risk, factors, of, noncommunicable, diseases])]). relacion([sujeto(['The']), verbo([report]), complemento([card, '(', 'RC)', project, provided, 'Thailand', with, an, opportunity, to, assess, 'PA', behaviors, in, children])]). relacion([sujeto(['Survey', results]), verbo([provided]), complemento([the, primary, source, for, the, 'RC'])]). relacion([sujeto(['These', first, data, on, patterns, of, activity, for, the, 'Thailand', 'RC', will, serve, to, guide, national, actions, and, advocacy, aimed, at]), verbo([increasing]), complemento(['PA', in, children])]). relacion([sujeto(['During', the, 'GAM,', 17]), verbo([leading]), complemento([researchers, and, policy, experts, from, 'Estonia', assessed, the, data, and, assigned, grades, for, each, of, the, 9, 'PA', indicators])]). relacion([sujeto(['In', 'addition,', recommendations, were]), verbo([provided]), complemento([for, further, actions, to, improve, the, grades])]). relacion([sujeto(['Evidence']), verbo([suggests]), complemento([that, 'PA', levels, of, 'Estonian', children, remain, very, 'low,', despite, moderately, supportive, 'social,', 'environmental,', and, regulatory, factors])]). relacion([sujeto(['There', are, many, challenges, to, overcome, in, supporting, and]), verbo([promoting]), complemento(['PA', of, children, and, youth, '(', 'eg,', 'cross-sectional', 'cooperation,', implementing, 'interventions,', changing, social, 'norms,', empowerment, of, parents, and, educational, 'institutions)'])]). relacion([sujeto(['The', grades, of, 9]), verbo([report]), complemento([card, indicators, were, assigned, in, accordance, with, the, survey, results, against, a, defined, 'benchmark:', 'A', is, 81, '%', to, 100, '%', ;, 'B', is, 61, '%', to, 80, '%', ;, 'C', is, 41, '%', to, 60, '%', ',', 'D', is, 21, '%', to, 40, '%', ;, 'F', is, 0, '%', to, 20, '%'])]). relacion([sujeto(['Interventions', and, policies, at, the, community, level, should, be, encouraged, to]), verbo([promote]), complemento([physical, activity, and, reduce, sedentary, behavior])]). relacion([sujeto(['Two', years, on, from, the, inaugural, 'Active', 'Healthy', 'Kids', 'Australia', '(', 'AHKA)', 'Physical', 'Activity', 'Report', 'Card,', there]), verbo([has]), complemento([been, little, to, no, change, with, the, majority, of, 'Australian', children, still, insufficiently, active])]). relacion([sujeto(['In', comparison, with, 2014, ',', 'Overall', 'Physical', 'Activity', 'Levels', was, again, assigned, a, 'D-', with, 'Organized', 'Sport', and, 'Physical', 'Activity', 'Participation']), verbo([increasing]), complemento([to, a, 'B', '(', was, 'B-)', and, 'Active', 'Transport', declining, to, a, 'C-', '(', was, 'C)'])]). relacion([sujeto(['The', traits]), verbo([associated]), complemento([with, physical, activity, were, also, graded, poorly, '(', 'C-', to, a, 'D)'])]). relacion([sujeto(['In', this, 'article,', we]), verbo([report]), complemento([the, grades, for, the, second, 'New', 'Zealand', 'Report', 'Card', on, 'Physical', 'Activity', for, 'Children', and, 'Youth,', which, represents, a, synthesis, of, available, 'New', 'Zealand', evidence, across, 9, core, indicators])]). relacion([sujeto(['The', grade, for, 'PA']), verbo([decreased]), complemento([slightly, from, the, 2014, report, 'card;', 'however,', there, was, an, improvement, in, grades, for, built, and, school, 'environments,', which, may, support, regional, and, 'national-level', initiatives, for, promoting, 'PA'])]). relacion([sujeto(['The', first, 'Danish', 'Report', 'Card', on, 'Physical', 'Activity', '(', 'PA)', for, 'Children', and, 'Youth', describes, 'Denmark\'s', efforts, in]), verbo([promoting]), complemento([and, facilitating, 'PA', and, 'PA', opportunities, for, children, and, youth])]). relacion([sujeto(['The']), verbo([report]), complemento([card, relies, primarily, on, a, synthesis, of, the, best, available, research, and, policy, strategies, identified, by, the, 'Report', 'Card', 'Research', 'Committee', consisting, of, a, wide, presentation, of, researchers, and, experts, within, 'PA', health, behaviors, and, policy, development])]). relacion([sujeto(['A', large, proportion, of, children, in, 'Denmark', do, not, meet, the, recommendations, for, 'PA', despite, the, favorable, investments, and, intensions, from, the, government, to, create, good, facilities, and]), verbo([promote]), complemento(['PA'])]). relacion([sujeto(['The']), verbo([report]), complemento([card, was, a, synthesis, of, the, best, available, evidence, on, the, performance, of, 'Zimbabwean', children, and, youth, on, key, physical, activity, '(', 'PA)', indicators])]). relacion([sujeto(['Zimbabwe', also, needs, to, prioritize, policies, and, investments, that]), verbo([promote]), complemento([greater, and, safe, participation, in, 'PA', among, children, and, youth])]). relacion([sujeto(['This', was, then, supported, by, 'peer-reviewed', papers, and, government]), verbo([reports]), complemento([identified, by, a, systematic, search, of, the, literature, written, in, 'English', or, 'Korean'])]). relacion([sujeto(['Though', the, final, grades, of, key, indicators, for, 'South', 'Korean', children, and, youth, are, not, 'satisfactory,']), verbo([increasing]), complemento([interests, and, investments, have, been, demonstrated, at, a, national, level])]). relacion([sujeto(['More', evidence, is]), verbo([required]), complemento([for, comprehensive, assessment, on, all, indicators, to, better, inform, policy, and, practice])]). relacion([sujeto(['Regular', participation, in, 'PA', is]), verbo([associated]), complemento([with, substantial, benefits, for, 'health,', cognitive, 'function,', and, social, inclusion])]). relacion([sujeto(['A', broad, policy, framework]), verbo([translated]), complemento([into, specific, actions, could, provide, unique, opportunities, to, bridge, the, gap, between, knowledge, and, 'practice,', and, contribute, to, social, integration, goals, in, a, postconflict, setting])]). relacion([sujeto(['Scotland']), verbo([has]), complemento([a, generally, favorable, environment, for, 'PA,', but, children, and, adolescents, have, low, 'PA', and, high, sedentary, behavior])]). relacion([sujeto(['Gaps', in, surveillance, included, lack, of, objectively, measured, 'PA,', no, surveillance, of, 'moderate-to-vigorous', 'PA', in, 'children,', summary, surveillance, data, not]), verbo([expressed]), complemento([in, ways, which, match, recommendations, '(', 'eg,', for, 'PA', in, young, 'children;', for, 'screen-time),', and, no, surveillance, of, 'Sport', 'Participation,', 'Active', and, 'Outdoor', 'Play,', or, 'Sitting'])]). relacion([sujeto(['The', main, goal, was, to, summarize, and, describe, the, current, state, of, child, and, youth, 'PA', to]), verbo([increase]), complemento([awareness, and, surveillance])]). relacion([sujeto(['The', systematic, methodology, that, underpins, the, 'Active', 'Healthy', 'Kids', 'Canada', 'Report', 'Card', was, adapted, and, applied, to, the, 'Polish']), verbo([report]), complemento([card])]). relacion([sujeto(['The', final, grades, show, a, strong, role, of, school, in]), verbo([providing]), complemento(['PA', for, children, and, youth, in, 'Poland'])]). relacion([sujeto(['However,', promotion, of, 'school-based', sport, participation, appears, to, be, insufficient, by, itself, to, sustainably]), verbo([promote]), complemento(['PA', in, this, group])]). relacion([sujeto(['The', 2016, 'Mexican', 'Report', 'Card', on, 'Physical', 'Activity', for, 'Children', and, 'Youth', aims, to, assess, how, 'Mexico', is, doing, in, terms, of]), verbo([providing]), complemento([physical, activity, '(', 'PA)', opportunities, for, 'Mexican', children, and, youth])]). relacion([sujeto(['Government', and, communities, are, far, from]), verbo([providing]), complemento([appropriate, and, sufficient, physical, activity, opportunities, for, children, and, youth])]). relacion([sujeto(['The', 'ParticipACTION', 'Report', 'Card', on, 'Physical', 'Activity', for, 'Children', and, 'Youth', is, the, most, comprehensive, assessment, of, child, and, youth, physical, activity, in, 'Canada', and]), verbo([provides]), complemento([an, update, or, &, 'quot;state', of, the, 'nation"', that, assesses, how, 'Canada', is, doing, at, promoting, and, facilitating, physical, activity, opportunities, for, children, and, youth])]). relacion([sujeto(['Sources', included, national, 'surveys,', 'peer-reviewed', 'literature,', and, gray, literature, such, as, government, and, nongovernment]), verbo([reports]), complemento([and, online, content])]). relacion([sujeto([')', 'Report', 'Card', on, 'Physical', 'Activity', for, 'Children', and, 'Youth']), verbo([provides]), complemento([a, comprehensive, evaluation, of, physical, activity, levels, and, factors, influencing, physical, activity, among, children, and, youth])]). relacion([sujeto(['The']), verbo([report]), complemento([card, includes, 10, 'indicators:', 'Overall', 'Physical', 'Activity,', 'Sedentary', 'Behavior,', 'Active', 'Transportation,', 'Organized', 'Sport', 'Participation,', 'Active', 'Play,', 'Health-related', 'Fitness,', 'Family', and, 'Peers,', 'School,', 'Community', and, the, 'Built', 'Environment,', and, 'Government', 'Strategies', and, 'Investments'])]). relacion([sujeto(['Continued', poor, grades]), verbo([suggest]), complemento([that, additional, work, is, required, to, provide, opportunities, for, 'U'])]). relacion([sujeto(['In', 'addition,', we]), verbo([reported]), complemento([on, 'Physical', 'Fitness', and, 'Motor', 'Proficiency', separately])]). relacion([sujeto(['We', also]), verbo([reported]), complemento([on, nutrition, indicators, including, 'Overweight', and, 'Under-nutrition', along, with, certain, key, behaviors, such, as, 'Fruit', and, 'Vegetable', 'Intake,', and, policies, and, programs, including, 'School', 'Nutrition', 'Programs', and, 'Tuck', 'Shops'])]). relacion([sujeto(['The', 2016, version, consolidates, and]), verbo([translates]), complemento([research, related, to, physical, activity, '(', 'PA)', among, children, and, youth, in, 'Wales,', and, aims, to, raise, the, awareness, of, 'children\'s', engagement, in, 'PA', and, sedentary, behaviors])]). relacion([sujeto(['Ten', 'PA', indicators, were, graded, using, the, 'Active', 'Healthy', 'Kids-Canada', 'Report', 'Card', methodology]), verbo([involving]), complemento([a, synthesis, and, expert, consensus, of, the, best, available, evidence])]). relacion([sujeto(['These', results, indicate, that, a, concerted, effort, is]), verbo([required]), complemento([to, increase, 'PA', and, decrease, sedentary, time, in, children, and, young, people, in, 'Wales'])]). relacion([sujeto(['Following', the, procedures, adopted, in, 2014, for, that, 'year\'s']), verbo([report]), complemento(['card,', comprehensive, searches, on, new, data, related, to, indicators, of, physical, activity, '(', 'PA)', were, done])]). relacion([sujeto(['Compared', with, 2014, there, were, several, differences, which, were]), verbo([caused]), complemento([by, changes, in, the, country, as, well, as, a, more, effective, evaluation, from, the, committee])]). relacion([sujeto(['The', decline, of, the, 'PA', habits, in, urban, centers]), verbo([reported]), complemento([in, 2014, are, accentuated, and, is, influencing, the, rural, areas, in, several, ways])]). relacion([sujeto(['The', 2016, 'Malaysia', 'Active', 'Healthy', 'Kids', 'Report', 'Card', aims, to, 'collect,', 'assess,', and, grade, current, and, comprehensive, data, on, physical, activity, '(', 'PA)', and]), verbo([associated]), complemento([factors, in, 'Malaysian', children, and, adolescents, aged, 5, to, 17, years])]). relacion([sujeto(['This']), verbo([report]), complemento([card, was, developed, following, the, 'Active', 'Healthy', 'Kids', 'Canada', 'Report', 'Card', protocol])]). relacion([sujeto(['The']), verbo([report]), complemento([card, demonstrates, that, 'Malaysian', children, and, adolescents, are, engaging, in, low, levels, of, 'PA', and, active, 'commuting,', high, levels, of, screen, 'time,', and, have, extremely, low, compliance, with, dietary, recommendations])]). relacion([sujeto(['More', efforts, are, needed, to, address, the, root]), verbo([causes]), complemento([of, physical, inactivity, while, increasing, the, opportunities, for, children, and, adolescents, to, be, more, physically, active])]). relacion([sujeto(['This', article, summarizes, the, results, of, the, 2016]), verbo([report]), complemento([card, and, provides, updated, evidence, on, the, current, situation, in, 'Nigeria'])]). relacion([sujeto(['A', substantial, number, of, 'Nigerian', children, and, youth, still]), verbo([have]), complemento([high, sedentary, 'behaviors,', overweight, and, obesity])]). relacion([sujeto(['Efforts', are, needed, to]), verbo([promote]), complemento(['PA', among, them])]). relacion([sujeto(['There', is, a, need, to, achieve, consensus, and, harmonize, methods, to, evaluate, 'PA', and, sedentary, behavior, to, monitor, changes, over, time, and, to, evaluate, the, effectiveness, of, policies, to]), verbo([promote]), complemento(['PA'])]). relacion([sujeto(['The', aim, of, this, article, is, to, summarize, the, procedure, and, results, from, the]), verbo([report]), complemento([card])]). relacion([sujeto(['The', included, data]), verbo([provides]), complemento([some, support, that, overall, 'PA', is, too, low, and, sedentary, behavior, is, too, high, for, almost, all, age, groups, in, 'Sweden,', even, with, the, many, national, policies, as, well, as, an, environment, that, is, favorable, to, the, promotion, of, 'PA'])]). relacion([sujeto(['\'', 'School', nurses, alone, cannot, fill, the, gap, in, sex, and, relationships, education, but, they, can]), verbo([act]), complemento([as, 'advocates,', providing, 'one-to-one', advice, for, 'pupils\''])]). relacion([sujeto(['Alzheimer\'s', disease, '(', 'AD),', the, most, common, neurodegenerative, disorder]), verbo([associated]), complemento([with, 'dementia,', not, only, severely, decreases, the, quality, of, life, for, its, 'victims,', but, also, brings, a, heavy, economic, burden, to, the, family, and, society])]). relacion([sujeto(['Unfortunately,', few, chemical, drugs, designed, for, clinical, applications]), verbo([have]), complemento([reached, the, expected, preventive, or, therapeutic, effect, so, 'far,', and, combined, with, their, significant, 'side-effects,', there, is, therefore, an, urgent, need, for, new, strategies, to, be, developed, for, 'AD', treatment])]). relacion([sujeto(['Traditional', 'Chinese', 'Medicine']), verbo([has]), complemento([accumulated, many, experiences, in, the, treatment, of, dementia, during, thousands, of, years, of, 'practice;', modern, pharmacological, studies, have, confirmed, the, therapeutic, effects, of, many, active, components, derived, from, 'Chinese', herbal, medicines, '(', 'CHM)'])]). relacion([sujeto(['Ginsenoside', 'Rg1,', extracted, from, 'Radix', 'Ginseng,', exerts, a, '[', 'Formula:', see, 'text]-secretase', inhibitor, effect, so, as, to]), verbo([decrease]), complemento(['A[Formula:', see, 'text]', aggregation])]). relacion([sujeto(['It', can, also]), verbo([inhibit]), complemento([the, apoptosis, of, neuron, cells])]). relacion([sujeto(['Tanshinone', 'IIA,', extracted, from, 'Radix', 'Salviae', 'miltiorrhizae,', and, 'baicalin,', extracted, from, 'Radix', 'Scutellariae[Formula:', see, 'text]', can]), verbo([inhibit]), complemento([the, oxidative, stress, injury, in, neuronal, cells])]). relacion([sujeto(['Icariin,', extracted, from, 'Epimedium', 'brevicornum,', can]), verbo([decrease]), complemento(['A[Formula:', see, 'text]', levels, and, the, hyperphosphorylation, of, tau, 'protein,', and, can, also, inhibit, oxidative, stress, and, apoptosis])]). relacion([sujeto(['Curcumin', can]), verbo([act]), complemento([on, 'A[Formula:', see, 'text]', and, tau, too])]). relacion([sujeto(['The', appraisal, assessed, evolocumab, as, monotherapy, or, in, combination, with, a, statin, '(', 'HMG-CoA', reductase, 'inhibitor)', with, or, without, 'ezetimibe,', or, in, combination, with, ezetimibe, '(', without, statin, 'therapy),', in, adult, patients, with, primary, hypercholesterolaemia, '(', which, includes, mixed, 'dyslipidaemia),', for, whom, statins, do, not]), verbo([provide]), complemento([optimal, control, of, their, 'low-density', lipoprotein, cholesterol, '(', 'LDL-C)', levels, 'and/or', for, whom, statins, are, contraindicated, or, not, tolerated])]). relacion([sujeto(['The', 'School', of, 'Health', and, 'Related', 'Research', 'Technology', 'Appraisal', 'Group', at, the, 'University', of, 'Sheffield', was, commissioned, to]), verbo([act]), complemento([as, the, independent, 'Evidence', 'Review', 'Group', '(', 'ERG)'])]). relacion([sujeto(['The', clinical, effectiveness, review]), verbo([found]), complemento([that, evolocumab, is, efficacious, at, lowering, 'LDL-C', but, that, there, was, uncertainty, regarding, its, impact, on, cardiovascular, disease, outcomes])]). relacion([sujeto(['Mobile', health, '(', 'mHealth)', applications]), verbo([provide]), complemento([an, excellent, opportunity, for, collecting, 'rich,', 'fine-grained', data, necessary, for, understanding, and, predicting, 'day-to-day', health, behavior, change, dynamics])]). relacion([sujeto(['To', explain, and, predict, the, dynamics, of, 'self-efficacy', and, predict, individual, performance, of]), verbo([targeted]), complemento(['behaviors,', the, 'self-efficacy', construct, is, implemented, as, a, 'theory-based', neurocognitive, simulation, of, the, interaction, of, behavioral, 'goals,', memories, of, past, 'experiences,', and, behavioral, performance])]). relacion([sujeto(['Securigenin-3-', 'O', -, 'inositol-(1 → 3)-β-glucopyranosyl-(1 → 4)-β-xylopyranoside', '(', 2, ')', and, 'securigenin-3-', 'O', -, 'α-rhamnopyranosyl-(1 → 4)-α-glucopyranoside', '(', 3, ')', were]), verbo([found]), complemento([as, new, natural, products])]). relacion([sujeto(['The', hypoglycemic, effect, was, due, to, an]), verbo([increase]), complemento([in, insulin, 'secretion;', the, insulin, levels, in, the, diabetic, mice, significantly, improved, and, were, comparable, with, those, in, healthy, animals, '(', 'P > 0'])]). relacion([sujeto([securidaca, seeds, were, identified, as, cardiac, glycosides, and, were]), verbo([found]), complemento([to, act, via, an, increase, of, insulin, levels, in, a, diabetic, mouse, model])]). relacion([sujeto(['Ectotherms']), verbo([have]), complemento([variable, body, temperatures, and, their, body, temperatures, influence, performance, 'and,', 'ultimately,', fitness])]). relacion([sujeto(['Therefore,', many, ectotherms, use, behavioral, thermoregulation, to, avoid, reduced, capacities]), verbo([associated]), complemento([with, body, temperatures, far, from, the, optimal, temperature, for, performance])]). relacion([sujeto(['Several', authors]), verbo([have]), complemento([proposed, that, thermal, niche, partitioning, in, response, to, interspecific, competition, is, a, mechanism, that, allows, the, coexistence, of, similar, species, of, ectotherms])]). relacion([sujeto(['Future', studies, should, include, sites, where, species, are, sympatric, and, sites, where, they, are, allopatric, to, rule, out, alternative, mechanisms, that]), verbo([cause]), complemento([differences, in, thermal, traits, between, coexisting, species])]). relacion([sujeto(['There', is, evidence, of, conservatism, in, the, evolution, of, most, thermal, traits, across, a, wide, range, of, 'taxa,', but, thermal, performance, curves, and, preferred, temperatures, do]), verbo([respond]), complemento([to, strong, selection, under, laboratory, conditions])]). relacion([sujeto(['Thus,', there, is, potential, for, selection, to]), verbo([act]), complemento([on, thermal, traits, in, response, to, interspecific, competition])]). relacion([sujeto(['Nevertheless,', more, stringent, tests, of, the, thermal, resource, partitioning, hypothesis, are]), verbo([required]), complemento([before, we, can, assess, whether, it, is, widespread, in, communities, of, ectotherms, in, nature])]). relacion([sujeto(['Several', biological, processes, as, well, as, infectious, 'agents,', physiological, or, environmental, 'stress,', and, perturbed, antioxidant, response, can]), verbo([promote]), complemento([oxidative, stress])]). relacion([sujeto(['Recent', studies]), verbo([have]), complemento([indicated, that, 'ROS', are, deleterious, to, 'cells,', leading, to, programmed, cell, death, '(', 'PCD)', at, high, concentrations])]). relacion([sujeto(['At', low, 'concentrations,', 'however,', 'ROS', can]), verbo([act]), complemento([as, signaling, molecules, in, a, variety, of, cellular, processes])]). relacion([sujeto(['We', then, discuss, how, the, antioxidant, defense, system]), verbo([acts]), complemento([as, an, antiviral, effector, to, limit, cell, damage])]). relacion([sujeto(['In', the, present, 'work,', we, examine, the, possibility, of, a, 'benzo-18-crown-6', ether, of, styrylquinoline, molecule, '(', 1, ')', in, acetonitrile, solvent, to]), verbo([act]), complemento([as, a, sensor, for, the, 'Ca(++)', cation, and, as, a, molecular, logical, gate])]). relacion([sujeto(['Furthermore', it, is, shown, that, 1, can]), verbo([act]), complemento([as, a, molecular, optical, switch, owing, to, its, ability, to, be, reversibly, protonated, 'and/or', 'Ca(++)', complexed, with, substantial, accompanying, differences, in, the, spectral, properties])]). relacion([sujeto(['In', deformation, 'processes,', the, presence, of, grain, boundaries]), verbo([has]), complemento([a, crucial, influence, on, dislocation, 'behavior;', these, boundaries, drastically, change, the, mechanical, properties, of, polycrystalline, materials])]). relacion([sujeto(['It']), verbo([has]), complemento([been, considered, that, grain, boundaries, act, as, effective, barriers, for, dislocation, 'glide,', but, the, origin, of, this, 'barrier-like', behavior, has, been, a, matter, of, conjecture, for, many, years])]). relacion([sujeto(['ACT', is, a, new, imaging, modality, that]), verbo([provides]), complemento([a, clear, visualization, of, stent, strut])]). relacion([sujeto(['Therefore', this, new, application]), verbo([has]), complemento([potential, to, become, the, noninvasive, option, for, 'follow-up', after, endovascular, surgery, using, stents])]). relacion([sujeto(['Two', case]), verbo([reports]), complemento([describing, a, new, technique, of, creating, a, repositionable, piezoelectric, bony, window, osteotomy, during, apicoectomy, in, order, to, preserve, bone, and, act, as, an, autologous, graft, for, the, surgical, site, are, described])]). relacion([sujeto(['Endodontic', microsurgery, of, anterior, teeth, with, an, intact, cortical, plate, and, large, periapical, lesion, generally]), verbo([involves]), complemento([removal, of, a, significant, amount, of, healthy, bone, in, order, to, enucleate, the, diseased, tissue, and, manage, root, ends])]). relacion([sujeto(['In', the]), verbo([reported]), complemento(['cases,', apicoectomy, was, performed, on, the, lateral, incisors, of, two, patients])]). relacion([sujeto(['Within', this, 'relationship,', the, presence, of, 'depression,', 'somatization,', 'hostility,', paranoid, 'ideation,', and, interpersonal, sensitivity, symptoms, at, a, subclinical, level, and, their, possible, input, on, infant, motor, competences]), verbo([has]), complemento([not, been, yet, considered])]). relacion([sujeto(['Both', positive, and, negative, correlations, were]), verbo([found]), complemento([between, maternal, perceived, 'symptomatology,', 'Somatization', '(', 'SOM),', 'Interpersonal', 'Sensitivity', '(', 'IS),', 'Depression', '(', 'DEP),', 'Hostility', '(', 'HOS),', and, 'Paranoid', 'Ideation', '(', 'PAR)', and, 'infants\'', motor, abilities])]). relacion([sujeto(['In', 'particular,', depressive, and, hostility, feelings, in, mothers, seemed, to]), verbo([induce]), complemento([an, infant, motor, behavior, characterized, by, a, major, control, of, the, environmental, space])]). relacion([sujeto(['When', mothers, perceived, a, higher, level, of, hostility, and, 'somatization,', their, babies, showed, difficulties, in, sharing, action, 'space,', such, as]), verbo([required]), complemento([in, the, development, of, stationary, positions, and, grasping, abilities])]). relacion([sujeto(['These', findings, 'suggest,', for, the, first, 'time,', that, even, in, a, 'non-clinical', 'sample,', 'mother\'s', 'perceived-symptoms', can, produce, important, consequences, not, in, infant, motor, development, as, a, 'whole,', but, in, some, specific, 'areas,', contributing, to, shape, the, 'infant\'s', motor, ability, and, 'his/her', capability, to]), verbo([act]), complemento([in, the, world])]). relacion([sujeto(['Reward', processing]), verbo([has]), complemento([been, robustly, linked, to, 'DA', 'activity;', 'thus,', examining, behavioral, effects, of, reward, anticipation, at, different, timing, 'intervals,', corresponding, to, different, putative, dopaminergic, 'dynamics,', may, help, in, characterizing, the, functional, role, of, these, dynamics])]). relacion([sujeto([',', 2003, ')', and, arguments, that, uncertainty, may]), verbo([act]), complemento([as, a, control, signal, increasing, environmental, monitoring, '(', 'Mushtaq', et, al])]). relacion([sujeto([',', 2011, ')', ',', we]), verbo([suggest]), complemento([that, task, information, and, reward, uncertainty, can, both, serve, as, &, 'quot;need', for, 'control"', signals, that, facilitate, learning, via, enhanced, 'monitoring,', and, that, this, activity, may, be, supported, by, a, ramping, profile, of, dopaminergic, activity])]). relacion([sujeto(['Recently,', our, group, identified, 72, genes, that]), verbo([interact]), complemento([with, 'Death', 'Caspase-1', '(', 'DCP-1)', proteins, in, 'Drosophila', by, genetic, screening, of, 15, ',', 0, 'EP', lines])]). relacion([sujeto(['Our', studies, revealed, that, 'ALFY,', 'BIRC4,', and, 'TAK1']), verbo([induced]), complemento(['autophagy,', while, 'SEC61A2,', 'N-PAC,', 'BIRC4,', 'WIPI1,', and, 'FALZ', increased, apoptotic, cell, death])]). relacion([sujeto(['BIRC4', was]), verbo([involved]), complemento([in, both, autophagy, and, apoptosis])]). relacion([sujeto(['Western', blot, analysis, and, luciferase, reporter, activity, indicated, that, 'ALFY,', 'BIRC4,', 'PDGFA,', and, 'TAK1']), verbo([act]), complemento([in, a, 'p53-dependent', 'manner,', whereas, 'CPSF1,', 'SEC61A2,', 'N-PAC,', and, 'WIPI1', appear, to, be, 'p53-independent'])]). relacion([sujeto(['Overexpression', of, 'BIRC4', and, 'TAK1']), verbo([caused]), complemento([upregulation, of, p53, and, accumulation, of, its, target, proteins, as, well, as, an, increase, in, p53, mRNA, 'levels,', suggesting, that, these, genes, are, involved, in, p53, transcription, and, expression, of, its, target, genes, followed, by, p53, protein, accumulation])]). relacion([sujeto(['In', 'conclusion,', apoptosis, 'and/or', autophagy]), verbo([mediated]), complemento([by, 'BIRC4', and, 'TAK1', may, be, regulated, by, p53, and, caspase, activity])]). relacion([sujeto(['These', novel, findings, may]), verbo([provide]), complemento([valuable, information, that, will, aid, in, a, better, understanding, of, the, roles, of, 'caspase-related', genes, in, human, cell, lines, and, be, useful, for, the, process, of, drug, discovery])]). relacion([sujeto(['Luteinizing', hormone, '(', 'LH)', rises, dramatically, during, and, after, 'menopause,', and]), verbo([has]), complemento([been, correlated, with, an, increased, incidence, of, 'Alzheimer\'s', disease, and, decreased, memory, performance, in, humans, and, animal, models])]). relacion([sujeto(['To', test, whether, 'LH']), verbo([acts]), complemento([directly, on, the, dorsal, hippocampus, to, affect, 'memory,', ovariectomized, female, rats, were, infused, with, either, the, 'LH-homologue', human, chorionic, gonadotropin, '(', 'hCG)', or, the, 'LH', receptor, antagonist, 'deglycosylated-hCG', '(', 'dg-hCG)'])]). relacion([sujeto(['Infusion', of, hCG, into, either, the, lateral, ventricle, or, the, dorsal, hippocampus]), verbo([caused]), complemento([significant, memory, impairments, in, ovariectomized, 'estradiol-treated', females])]). relacion([sujeto(['Consistent', with, 'this,', infusion, of, the, 'LH', antagonist, 'dg-hCG', into, the, dorsal, hippocampus]), verbo([caused]), complemento([an, amelioration, of, memory, deficits, in, ovariectomized, females])]). relacion([sujeto(['Furthermore,', the, 'gonadotropin-releasing', hormone, antagonist, 'Antide,', failed, to]), verbo([act]), complemento([in, the, hippocampus, to, affect, memory])]). relacion([sujeto(['Previous', studies, of, the, causal, relationship, between, safety, climate, and, safety, compliance, demonstrate, that, the, propensity, to]), verbo([act]), complemento([in, accordance, with, prevailing, rules, and, procedures, is, influenced, to, a, large, degree, by, 'workers\'', safety, climate])]). relacion([sujeto(['The', causal, relationship, was]), verbo([found]), complemento([to, be, stable, across, the, 'period,', thereby, increasing, the, reliability, and, the, predictive, validity, of, the, factor, structure])]). relacion([sujeto(['Those', admitted, voluntarily]), verbo([reported]), complemento([higher, levels, of, perceived, coercion, from, internal, 'sources,', and, those, admitted, involuntarily, perceived, significantly, higher, coercion, from, legal, sources])]). relacion([sujeto(['No', differences, between, groups, were]), verbo([found]), complemento([with, the, other, tests])]). relacion([sujeto(['Our', results]), verbo([suggested]), complemento([that, assumptions, about, involuntary, admissions, should, be, evaluated, carefully, to, determine, how, best, to, alleviate, counterproductive, feelings, of, coercion, when, a, coerced, admission, is, planned])]). relacion([sujeto(['Up', to, now, more, than, 60, proteins]), verbo([have]), complemento([been, described, that, act, primarily, as, regulators, of, intracellular, transport])]). relacion([sujeto(['Rab', 'GTPases', are, mostly, located, at, the, intracellular, 'membranes,', where, they]), verbo([provide]), complemento([connections, to, motor, proteins, and, to, the, cytoskeleton, and, control, various, steps, of, the, traffic, pathways, including, the, formation, and, movement, of, vesicles, or, membrane, fusion, controlling, 'secretion,', 'endocytosis,', recycling, and, degradation, of, proteins])]). relacion([sujeto(['The', number, of, identified, diseases]), verbo([associated]), complemento([with, mutations, in, 'Rab', proteins, or, their, cooperating, partners, increases, and, the, evidence, for, the, involvement, of, 'Rab', to, the, human, pathologies, such, as, the, immune, 'failure,', obesity, and, 'diabetes,', 'Alzheimers', disease, or, hereditary, genetic, diseases, is, growing])]). relacion([sujeto(['The', malfunctions, of, 'Rab', proteins]), verbo([caused]), complemento([by, mutations, or, aberrant, posttranslational, modifications, lead, to, changes, in, the, protein, and, vesicle, 'trafficking,', which, play, a, crucial, role, in, the, formation, and, development, of, cancer, and, the, deregulation, of, 'Rab', expression, frequently, influences, the, 'migration,', 'invasion,', proliferation, and, drug, resistance, of, the, tumor, cells])]). relacion([sujeto(['The', authors, declare, they]), verbo([have]), complemento([no, potential, conflicts, of, interest, concerning, 'drugs,', 'products,', or, services, used, in, the, study])]). relacion([sujeto(['Endoplasmic', reticulum, chaperones, are, stress]), verbo([induced]), complemento([proteins, capable, of, translocation, into, 'cytosol,', cell, membrane, or, extracellular, space])]). relacion([sujeto(['The', chaperones, are, transported, from, the, endoplasmic, reticulum, particularly, under, endoplasmic, reticulum, stress, 'conditions,', while, their, constitutive, extracellular, expression, was]), verbo([found]), complemento([in, many, cancers])]). relacion([sujeto(['Cell', surface, or, extracellular, endoplasmic, reticulum, chaperones, take, up, distinct, functions, compared, to, their, endoplasmic, reticulum, resident, variants, because, they]), verbo([act]), complemento([like, multifunctional, receptors, and, thus, affect, cell, signaling, and, proliferation])]). relacion([sujeto(['Well', described, cancer, cell, surface, endoplasmic, reticulum, chaperones, include, 'GRP78,', 'GRP94,', calreticulin, and, calnexin, that, are]), verbo([involved]), complemento([in, cancer, cell, signaling, in, different, ways])]). relacion([sujeto(['The', attention, is, also, paid, to, immunogenic, properties, of, 'membrane-localized', chaperones, for, their, ability, to]), verbo([participate]), complemento([in, immune, reactions])]). relacion([sujeto(['The', authors, declare, they]), verbo([have]), complemento([no, potential, conflicts, of, interest, concerning, 'drugs,', 'products,', or, services, used, in, the, study])]). relacion([sujeto(['Here,', we, aim, to, systematically, identify, the, genetic, factors]), verbo([causing]), complemento([ovarian, cancer, and, find, the, accurate, diagnostic, and, therapeutic, targets, for, ovarian, cancer])]). relacion([sujeto(['We', collected, the, known, archived, ovarian, 'cancer-related', genes, from, the, databases, used, as, the, investigated]), verbo([targets]), complemento([and, employed, the, minimum, redundancy, maximum, relevance, and, random, forest, classification, to, identify, the, novel, ovarian, 'cancer-related', genes, in, addition, to, the, known, ones])]). relacion([sujeto(['We']), verbo([found]), complemento([out, the, genetic, terms, to, interpret, the, mechanism, of, ovarian, cancer])]). relacion([sujeto(['These', candidates, can]), verbo([act]), complemento([as, expression, biomarkers, for, clinical, detection, and, they, achieved, a, 100, '%', accuracy])]). relacion([sujeto(['Intestinal', inflammation, can, impair, mucosal, 'healing,', thereby, establishing, a, vicious, cycle]), verbo([leading]), complemento([to, chronic, inflammatory, bowel, disease, '(', 'IBD)'])]). relacion([sujeto(['Here', we]), verbo([report]), complemento([that, 'CD4(+)', 'T', cells, isolated, from, patients, with, 'IBD', produce, high, levels, of, 'interleukin-22', binding, protein, '(', 'IL-22BP),', the, endogenous, inhibitor, of, the, 'tissue-protective', cytokine, 'IL-22'])]). relacion([sujeto(['Using', mouse, 'models,', we, demonstrate, that, 'IBD', development]), verbo([requires]), complemento(['T', 'cell-derived', 'IL-22BP'])]). relacion([sujeto(['Lastly,', intestinal, 'CD4(+)', 'T', cells, isolated, from, 'IBD', patients, responsive, to, treatment, with, antibodies, against, tumor, necrosis, 'factor-α', '(', 'anti-TNF-α),', the, most, effective, known, 'IBD', 'therapy,', exhibited, reduced, amounts, of, 'IL-22BP', expression, but, still]), verbo([expressed]), complemento(['IL-22'])]). relacion([sujeto(['Our', findings]), verbo([suggest]), complemento([that, 'anti-TNF-α', therapy, may, act, at, least, in, part, by, suppressing, 'IL-22BP', and, point, toward, a, more, specific, potential, therapy, for, 'IBD'])]). relacion([sujeto(['Although', great, apes, share, with, humans, many, 'social-cognitive', 'skills,', they]), verbo([have]), complemento([repeatedly, failed, experimental, tests, of, such, 'false-belief', understanding])]). relacion([sujeto(['We', use, an, anticipatory, looking, test, '(', originally, developed, for, human, 'infants)', to, show, that, three, species, of, great, apes, reliably, look, in, anticipation, of, an, agent]), verbo([acting]), complemento([on, a, location, where, he, falsely, believes, an, object, to, 'be,', even, though, the, apes, themselves, know, that, the, object, is, no, longer, there])]). relacion([sujeto(['Our', results]), verbo([suggest]), complemento([that, great, apes, also, 'operate,', at, least, on, an, implicit, 'level,', with, an, understanding, of, false, beliefs])]). relacion([sujeto(['These', factors]), verbo([act]), complemento([on, a, substrate, of, individual, predisposition, derived, from, the, composite, effects, of, inherited, 'DNA', variation, and, a, range, of, environmental, exposures, experienced, throughout, the, life, course])]). relacion([sujeto(['Drug']), verbo([release]), complemento([profile, confirmed, the, redox, responsive, behavior, of, polymeric, nanoparticles, with, '∼72%', drug, release, at, pH, 5.5, in, presence, of, 10, mM, 'GSH', as, compared, to, '∼18%', drug, release, at, pH, 7.4])]). relacion([sujeto(['Fluorescence']), verbo([activated]), complemento([cell, sorting, '(', 'FACS)', studies, demonstrated, higher, apoptosis, '(', '∼80%)', as, compared, to, 'non-conjugated', polymeric, nanoparticles, '(', 20, '%', ')', in, 'MCF-7', cell, line])]). relacion([sujeto(['Thus,', it, is, envisaged, that, these, redox, responsive, polymeric, nanocarriers]), verbo([act]), complemento([as, 'Trojan', horses, in, cancer, therapeutics])]). relacion([sujeto(['BnbZIP2']), verbo([has]), complemento([a, 1416, base, pair, open, reading, 'frame,', encoding, a, 471, amino, acid, protein, containing, a, characteristic, bZIP, domain, and, a, leucine, zipper])]). relacion([sujeto(['Transcripts', of, 'BnbZIP2', were]), verbo([found]), complemento([in, various, tissues, in, 'ramie,', with, significantly, higher, levels, in, female, and, male, flowers])]). relacion([sujeto(['Its', expression, was]), verbo([induced]), complemento([by, 'drought,', high, 'salinity,', and, abscisic, acid, treatments])]). relacion([sujeto(['Analysis', of, the, 'cis-elements', in, promoters, of, 'BnbZIP2', identified, 'cis-acting', elements]), verbo([involved]), complemento([in, 'growth,', developmental, 'processes,', and, a, variety, of, stress, responses])]). relacion([sujeto(['Thus,', 'BnbZIP2', may]), verbo([act]), complemento([as, a, positive, regulator, in, 'plants\'', response, to, 'high-salinity', stress, and, be, an, important, candidate, gene, for, molecular, breeding, of, 'salt-tolerant', plants])]). relacion([sujeto(['Infections']), verbo([caused]), complemento([by, 'Mycobacterium', tuberculosis, and, other, mycobacteria, are, major, challenges, for, global, public, health])]). relacion([sujeto(['Particularly', worrisome, are, infections]), verbo([caused]), complemento([by, 'multidrug-resistant', 'bacteria,', which, are, increasingly, difficult, to, treat, because, of, the, loss, of, efficacy, of, the, current, antibacterial, 'agents,', a, problem, that, continues, to, escalate, worldwide])]). relacion([sujeto(['There']), verbo([has]), complemento([been, a, limited, interest, and, investment, on, the, development, of, new, antibacterial, agents, in, the, past, decades])]). relacion([sujeto(['This']), verbo([has]), complemento([led, to, the, current, 'situation,', in, which, there, is, an, urgent, demand, for, innovative, therapeutic, alternatives, to, fight, infections, caused, by, 'multidrug-resistant', 'pathogens,', such, as, 'multidrug-resistant', tuberculosis])]). relacion([sujeto(['The', identification, of, compounds, that, can]), verbo([act]), complemento([as, adjuvants, in, antimycobacterial, therapeutic, regimens, is, an, appealing, strategy, to, restore, the, efficacy, lost, by, some, of, the, antibiotics, currently, used, and, shorten, the, duration, of, the, therapeutic, regimen])]). relacion([sujeto(['In', this, 'work,', by, setting, 'Mycobacterium', smegmatis, as, a, model, 'organism,', we]), verbo([have]), complemento([developed, a, methodological, strategy, to, 'identify,', in, a, fast, and, simple, 'approach,', compounds, with, antimycobacterial, activity, or, with, potential, adjuvant, 'properties,', by, either, inhibition, of, efflux, or, other, unrelated, mechanisms])]). relacion([sujeto(['Such', an, approach, may]), verbo([increase]), complemento([the, rate, of, identification, of, promising, 'molecules,', to, be, further, explored, in, pathogenic, models, for, their, potential, use, either, as, antimicrobials, or, as, 'adjuvants,', in, combination, with, available, therapeutic, regimens, for, the, treatment, of, mycobacterial, infections])]). relacion([sujeto(['Moreover,', depending, on, whether, the, jammer, node]), verbo([has]), complemento([the, global, channel, state, information, '(', 'CSI)', of, both, the, legitimate, channel, and, the, 'eavesdropper\'s', 'channel,', it, explores, a, 'zero-forcing', beamforming, '(', 'ZFB)', scheme, or, a, 'null-space', artificial, noise, '(', 'NAN)', scheme, to, confound, the, eavesdropper, while, avoiding, the, interference, to, the, legitimate, user])]). relacion([sujeto(['Numerical', results, are]), verbo([provided]), complemento([to, verify, the, theoretical, analysis, and, illustrate, the, impact, of, key, system, parameters, on, the, secrecy, performance])]). relacion([sujeto(['Existing', implantable, stimulators, use, powering, approaches, that, result, in, stiff, and, bulky, systems, or, result, in, systems, incapable, of, producing, the, current, magnitudes]), verbo([required]), complemento([for, neuromuscular, stimulation])]). relacion([sujeto(['The', implants]), verbo([act]), complemento([as, rectifiers, of, 'HF', current, that, flows, through, the, tissues, by, galvanic, 'coupling,', transforming, this, current, into, low, frequency, current, capable, of, performing, neuromuscular, stimulation])]). relacion([sujeto(['The', participants, were]), verbo([recruited]), complemento([from, existing, support, groups])]). relacion([sujeto(['Others']), verbo([reported]), complemento([that, the, 'GP', did, not, act, when, he, or, she, should, have, been, concerned, about, their, adverse, life, situation])]). relacion([sujeto(['The', 'GP', may, contribute, to, better, 'long-term', psychosocial, outcomes, by]), verbo([ensuring]), complemento([that, the, adolescents, receive, information, about, the, 'parent\'s', illness, and, have, someone, to, talk, to, about, their, feelings, and, experiences])]). relacion([sujeto(['The', 'GP']), verbo([has]), complemento([a, potential, to, support, them, by, taking, the, initiative, to, talk, about, their, life, 'situation,', and, by, recognizing, their, special, efforts])]). relacion([sujeto(['Adolescents', experience, unpredictability, in, life, and, strive, to]), verbo([find]), complemento([balance, between, their, own, needs, and, the, restrictions, caused, by, parental, illness])]). relacion([sujeto(['The', 'GP', may, help, them, by]), verbo([recognizing]), complemento([their, experiences, and, 'struggles,', give, 'information,', offer, talks, and, support, coping, strategies])]). relacion([sujeto(['The', best, studied, heat, shock, protein, is, 'HSP70,', which, is, known, to]), verbo([act]), complemento([as, a, molecular, chaperone, to, maintain, cellular, homeostasis, and, inhibit, protein, aggregation, in, response, to, stress])]). relacion([sujeto(['While', early, animal, studies]), verbo([suggested]), complemento([that, increasing, 'HSP70', in, the, heart, '(', using, a, 'transgenic,', gene, transfer, or, pharmacological, 'approach)', provided, cardiac, protection, against, acute, cardiac, 'stress,', recent, studies, have, found, no, benefit, of, increasing, 'HSP70', in, mouse, models, of, chronic, cardiac, stress])]). relacion([sujeto(['As', 'HSP70']), verbo([has]), complemento([been, considered, a, potential, therapeutic, 'target,', it, is, important, to, comprehensively, assess, 'HSP70', therapies, in, preclinical, models, of, acute, and, chronic, cardiac, disease])]). relacion([sujeto(['From', 'Balint', groups, that, help, participants, to, tolerate, uncertainty, to, 'narrative-based', supervision, that, poses, challenging, 'self-reflective', 'questions,', each, chapter]), verbo([provides]), complemento([a, description, of, group, intervention, 'design,', theoretical, 'context,', the, structure, for, 'facilitation,', and, outcome, data, on, impact])]). relacion([sujeto(['The', book, is, a, powerfully, thoughtful, and, detailed, exploration, of, the, often, overlooked, topic, of, not, understanding, or, knowing, how, to]), verbo([act]), complemento([in, the, best, interest, of, a, patient])]). relacion([sujeto(['(', 'PsycINFO', 'Database', 'Record', 'Federally', 'Qualified', 'Health', 'Centers--commonly', referred, to, as, 'Community', 'Health', 'Centers', '(', 'CHCs)--serve', as, a, safety, net, for, people, who, did, not]), verbo([gain]), complemento([health, insurance, under, the, 'Affordable', 'Care', 'Act', '(', 'ACA),', including, those, immigrants, not, eligible, for, 'Medicaid', or, health, insurance, exchange, coverage])]). relacion([sujeto(['ACA-driven', changes, in, health, insurance, 'coverage,', 'funding,', and, related, policy]), verbo([have]), complemento([created, new, challenges, for, these, safety, net, organizations])]). relacion([sujeto(['This', policy, brief]), verbo([reports]), complemento([the, findings, from, analyses, of, the, 'U'])]). relacion([sujeto(['The', study]), verbo([found]), complemento([that, most, 'CHCs', now, see, more, 'patients,', including, significant, numbers, without, insurance])]). relacion([sujeto(['The', 'ACA']), verbo([has]), complemento([brought, new, resources, to, 'CHCs', but, has, also, reinforced, 'challenges,', including, the, need, for, stable, revenue, 'streams,', sufficient, staffing, 'support,', and, assistance, in, leveraging, new, reimbursement, mechanisms])]). relacion([sujeto(['As', health, care, reform, continues, to, take, 'effect,', it, will, be, important, to, monitor, the, public, versus, private, contributions, to, state, health, care, expenditures, to]), verbo([ensure]), complemento([that, funds, are, being, distributed, both, efficiently, and, equitably])]). relacion([sujeto(['In', 2015, -, 2016, a, pilot, mandatory, training, on, 'HAI']), verbo([targeted]), complemento([to, 'HCWs', was, organized, in, the, 450, bed, teaching, hospital, 'Sant\'Andrea', in, 'Rome'])]). relacion([sujeto(['By', adopting, the, &, 'quot;Impact/control', 'matrix"', prioritization, 'tool,', the, relative, level, of, impact, '(', risk, in]), verbo([causing]), complemento([or, favoring, 'HAI)', and, control, '(', possibility, for, 'HCWs', to, prevent, 'HAI)', attributed, by, the, participants, to, the, issues, associated, to, 'HAI', during, their, working, groups, was, evaluated])]). relacion([sujeto(['Overall,', 34, 'physicians,', 43, nurses, and, 15, non, clinical, professionals]), verbo([participated]), complemento([actively, in, seven, 'courses,', identifying, 58, different, issues, related, to, 'HAI,', which, were, reported, 128, times])]). relacion([sujeto(['Results', showed, frequently, 'that,', within, the, same, type, of, 'issue,', 'HCW', referred, various, levels, of, impact, '(', risk, in]), verbo([causing]), complemento([or, favoring, 'HAI)', and, personal, control, '(', possibility, for, 'HCW', to, prevent, 'HAI)'])]). relacion([sujeto(['Overall', staff, shortage, was, the, most]), verbo([reported]), complemento([problem, by, 'HCW', in, our, hospital])]). relacion([sujeto(['Also', hand, washing, was, regarded, as, a, main, 'problem,', but, 'HCW']), verbo([expressed]), complemento([the, feeling, that, individuals, could, act, more, successfully, on, this, issue, '(', high, or, medium, 'control)'])]). relacion([sujeto(['Results', showed, that, staff, frequently, did, not, know, how, to, handle, correctly, 'visitors,', similarly, many, colleagues]), verbo([expressed]), complemento([some, difficulty, in, communicating, information, to, patients, and, relatives, on, 'HAI'])]). relacion([sujeto(['HCW']), verbo([expressed]), complemento([satisfaction, for, the, course, approac])]). relacion([sujeto(['Real-time', 'PCR', analysis, showed, that, the, expression, level, of, 'LcIDL1', accumulated, gradually, following, flower, 'abscission,', and, it, was, obviously]), verbo([induced]), complemento([by, fruit, 'abscission-promoting', treatments])]). relacion([sujeto(['Transgenic', plants]), verbo([expressing]), complemento(['LcIDL1', in, 'Arabidopsis', revealed, a, role, of, 'LcIDL1', similar, to, 'IDA', in, promoting, floral, organ, abscission])]). relacion([sujeto(['Moreover,', ectopic, expression, of, 'LcIDL1', in, 'Arabidopsis']), verbo([activated]), complemento([the, expression, of, 'abscission-related', genes])]). relacion([sujeto(['Taken', 'together,', our, findings]), verbo([provide]), complemento([evidence, that, 'LcIDL1', may, act, as, a, key, regulator, in, control, of, abscission])]). relacion([sujeto(['Neutrophils', play, significant, regulatory, roles, within, the, tumor, microenvironment, by, directly]), verbo([promoting]), complemento([tumor, progression, that, leads, to, poor, clinical, outcomes])]). relacion([sujeto(['Identifying', the, tumor]), verbo([associated]), complemento([molecules, that, regulate, neutrophil, infiltration, into, tumors, may, provide, new, and, specific, therapeutic, targets, for, cancer, treatment])]). relacion([sujeto(['The', 'a2-isoform', of, vacuolar, 'ATPase', '(', 'a2V)', is, uniquely, and, highly]), verbo([expressed]), complemento([on, cancer, cell, plasma, membrane])]). relacion([sujeto(['Cancer', cells, secrete, a, peptide, from, a2V, '(', 'a2NTD)', that]), verbo([promotes]), complemento([the, 'pro-tumorigenic', properties, of, neutrophils])]). relacion([sujeto(['This']), verbo([provides]), complemento([a2V, the, propensity, to, control, neutrophil, migration])]). relacion([sujeto(['Here,', we]), verbo([report]), complemento([that, the, treatment, of, human, neutrophils, with, recombinant, a2NTD, leads, to, neutrophil, adherence, and, polarization])]). relacion([sujeto(['Moreover,', a2NTD, treatment]), verbo([activates]), complemento([surface, adhesion, 'receptors,', as, well, as, 'FAK', and, 'Src', kinases, that, are, essential, regulators, of, the, migration, process, in, neutrophils])]). relacion([sujeto(['Functional', analysis]), verbo([reveals]), complemento([that, a2NTD, can, act, as, a, 'chemo-attractant', and, promotes, neutrophil, migration])]). relacion([sujeto(['Confirmatory', assays, demonstrate, that, the]), verbo([promoted]), complemento([migration, of, a2Neuɸ, was, dependent, on, the, autocrine, secretion, of, 'IL-8', from, a2Neuɸ])]). relacion([sujeto(['These', findings, demonstrate, for, the, first, time, the, direct, regulatory, role, of, cancer]), verbo([associated]), complemento(['a2-isoform', 'V-ATPase', on, neutrophil, 'migration,', suggesting, a2V, as, a, potential, target, for, cancer, therapy])]). relacion([sujeto(['Antimicrobial', peptides, '(', 'AMPs)', are, short, cationic, 'host-defense', molecules, that]), verbo([provide]), complemento([the, early, stage, of, protection, against, invading, microbes])]). relacion([sujeto(['They', also]), verbo([have]), complemento([important, modulatory, roles, and, act, as, a, bridge, between, innate, and, acquired, immunity])]). relacion([sujeto(['The', types, and, functions, of, oral, 'AMPs', were, reviewed, and, experimental]), verbo([reports]), complemento([on, the, use, of, natural, 'AMPs', and, their, synthetic, mimics, in, caries, and, pulpal, infections, were, discussed])]). relacion([sujeto(['Because', of, their, immunomodulatory, and, wound, healing, 'potentials,', 'AMPs']), verbo([stimulate]), complemento(['pro-inflammatory', cytokine, 'production,', recruit, host, defense, cells, and, regulate, 'immuno-inflammatory', responses, in, the, vicinity, of, the, pulp, and, periapex])]). relacion([sujeto(['Despite', the, presence, of, commercialization, hurdles, and, scientific, 'challenges,', interests, in, using, antimicrobial, peptides, as, therapeutic, alternatives, and, adjuvants, to, combat, pathogenic, biofilms]), verbo([have]), complemento([never, been, foreshortened])]). relacion([sujeto(['Not', only, do, these, cationic, peptides, possess, rapid, killing, 'ability,', their, 'multi-modal', mechanisms, of, action, render, them, advantageous, in]), verbo([targeting]), complemento([different, biofilm, 'sub-populations'])]). relacion([sujeto(['Moreover,', it, is, assumed, that, speech, intelligibility, is, more, affected, in, the, event, of, background, noises, that]), verbo([induce]), complemento([a, higher, cognitive, 'load,', i])]). relacion([sujeto(['In', order, to, develop, effective, rehabilitation, 'strategies,', it, is, indispensable, to, know, how, these, different, degrading, factors]), verbo([act]), complemento([upon, speech, perception])]). relacion([sujeto(['We', applied, stationary, and, amplitude]), verbo([modulated]), complemento(['speech-weighted', 'noise,', which, are, two, types, of, energetic, 'maskers,', and, unintelligible, 'speech,', which, causes, informational, masking, in, addition, to, energetic, masking])]). relacion([sujeto(['Our', results, indicate, 'that,', even, when, audiometric, thresholds, are, within, normal, limits, up, to, 4, &, 'nbsp;kHz,', irrespective, of, threshold, elevations, at, higher, 'frequencies,', and, there, is, no, indication, of, even, mild, cognitive, 'impairment,', masked, speech, perception, declines, by, middle, age, and]), verbo([decreases]), complemento([further, on, to, older, age])]). relacion([sujeto(['Hearing', impairment, seems, to, be, the, main, factor, underlying, speech, perception, problems, in, background, noises, that]), verbo([cause]), complemento([energetic, masking])]). relacion([sujeto(['However,', in, the, event, of, informational, 'masking,', which]), verbo([induces]), complemento([a, higher, cognitive, 'load,', age, appears, to, explain, a, significant, part, of, the, communicative, impairment, as, well])]). relacion([sujeto(['We']), verbo([suggest]), complemento([that, the, degrading, effect, of, age, is, mediated, by, deficiencies, in, temporal, processing, and, central, executive, functions])]). relacion([sujeto(['This', study, may, contribute, to, the, improvement, of, auditory, rehabilitation, programs, aiming, to]), verbo([prevent]), complemento([aging, persons, from, missing, out, on, 'conversations,', 'which,', in, 'turn,', will, improve, their, quality, of, life])]). relacion([sujeto(['The', modifications, of, electroencephalographic, '(', 'EEG)', power, spectra]), verbo([associated]), complemento([with, 'A/T', training, was, also, investigated])]). relacion([sujeto(['Fifty', subjects, were, enrolled, in, the, study, and, randomly, assigned, to, receive, ten, sessions, of, 'A/T', training, '[', neurofeedback, group, '(', 'NFG)=25],', or, to]), verbo([act]), complemento([as, controls, '[', waiting, list, group, '(', 'WLG)=25]'])]). relacion([sujeto(['Furthermore,', 'A/T', training, was]), verbo([associated]), complemento([with, significant, a, increase, of, resting, 'EEG', alpha, power, in, several, brain, areas, involved, in, 'FC', '(', e])]). relacion([sujeto(['Taken', 'together,', our, results, showed, that, ten, sessions, of, 'A/T', training, are]), verbo([associated]), complemento([with, a, decrease, of, 'self-reported', 'FC', in, a, 'non-clinical', sample])]). relacion([sujeto(['These', findings]), verbo([suggest]), complemento([that, this, 'brain-directed', intervention, may, be, useful, in, the, treatment, of, dysfunctional, eating, behaviors, characterized, by, 'FC'])]). relacion([sujeto(['Various', 'preclinical/clinical', studies, support, the, effectiveness, of, ketoprofen, in, 'periodontitis;', 'however,', the, literature]), verbo([reveals]), complemento([that, novel, delivery, systems, have, been, less, explored, for, the, drug, in, periodontitis])]). relacion([sujeto(['Viscosity', and, texture, studies, showed, good, adhesion, and, 'smoothness,', which, are, desired, for]), verbo([enhanced]), complemento([permeation])]). relacion([sujeto(['The', results]), verbo([lead]), complemento([to, the, conclusion, that, proniosomes, can, act, as, a, promising, carrier, and, can, be, effectively, used, for, improved, ketoprofen, delivery, in, periodontal, pockets])]). relacion([sujeto(['Here,', we]), verbo([report]), complemento([the, decrease, of, 'JA-sensitivity', and, enhancement, of, tolerance, to, salt, and, 'PEG', stresses, in, 'Arabidopsis', overexpressing, apple, 'MdJAZ2'])]). relacion([sujeto(['JAZ', proteins, are, the]), verbo([targets]), complemento([of, the, 'SCF(COI1)', complex, and, act, as, the, negative, regulators, in, 'JA', signalling, pathway])]). relacion([sujeto(['However,', there, are, no]), verbo([reports]), complemento([regarding, the, biological, function, of, apple, 'JAZ', genes])]). relacion([sujeto(['Yeast', 'two-hybrid', and, bimolecular, fluorescence, complementation, assays, revealed, that, 'MdJAZ2', could, form, 'homo-', and, 'heteromers,', and, also]), verbo([interact]), complemento([with, 'F-box', protein, 'MdCOI1'])]). relacion([sujeto(['Overexpression', of, 'MdJAZ2']), verbo([conferred]), complemento([impaired, 'JA-sensitivity', in, transgenic, 'Arabidopsis,', including, 'JA-mediated', root, growth, 'inhibition,', susceptibility, to, the, bacterial, pathogen, 'Pst', 'DC3000,', and, the, expression, of, 'JA', response, genes])]). relacion([sujeto(['Together,', our, findings]), verbo([suggest]), complemento([that, apple, 'MdJAZ2', was, not, only, involved, in, the, 'JA', response, but, also, played, roles, in, stress, tolerance])]). relacion([sujeto(['In', this, 'manner,', we]), verbo([reveal]), complemento([aspects, of, the, electronic, structure, related, to, electron, localization, and, observations, consistent, with, conductivity, anisotropy, between, the, 'ab-plane', and, 'c-axis'])]). relacion([sujeto(['The', energetic, position, of, the, states, in, the, band, gap]), verbo([suggest]), complemento([that, they, are, highly, localized, and, may, act, as, recombination, centres])]). relacion([sujeto(['Polarization', dependent, 'X-ray', absorption, spectra]), verbo([reveal]), complemento([anisotropy, in, the, electronic, structure, between, the, 'ab-plane', and, 'c-axis'])]). relacion([sujeto(['These', insights, into, the, electronic, structure, are, discussed, in, the, context, of, existing, experimental, and, theoretical]), verbo([reports]), complemento([regarding, charge, transport, in, 'BiVO4'])]). relacion([sujeto(['The', best, existing, predictive, models, rely, on, several, months, of, baseline, data, and]), verbo([have]), complemento([only, been, validated, in, clinical, trial, research, datasets])]). relacion([sujeto(['We']), verbo([found]), complemento([that, a, random, forest, model, using, only, baseline, data, could, accurately, predict, disease, progression, for, a, clinical, trial, research, dataset, as, well, as, a, population, of, patients, being, treated, at, a, tertiary, care, clinic])]). relacion([sujeto(['Finally,', we]), verbo([found]), complemento([that, only, the, 'RF', 'Model', was, unbiased, and, was, less, subject, to, overfitting, than, either, of, the, other, two, models, when, applied, to, a, clinic, population])]). relacion([sujeto(['Melanoma-associated', spongiform, scleropathy, was, an, incidental]), verbo([finding]), complemento([in, an, 87, -, 'year-old', woman, with, oculodermal, melanocytosis, treated, for, primary, orbital, melanoma])]). relacion([sujeto(['All', previously]), verbo([reported]), complemento([cases, of, this, scleropathy, have, been, associated, with, uveal, melanoma])]). relacion([sujeto(['This', is, the, first, case, of, a, 'so-called', 'melanoma-associated', spongiform, scleropathy]), verbo([reported]), complemento([in, an, eye, without, uveal, melanoma])]). relacion([sujeto(['Archwires']), verbo([act]), complemento([as, gears, to, move, teeth, with, 'light,', continuous, forces])]). relacion([sujeto(['However,', the, intraoral, use, of, orthodontic, archwires, is, liable, to, surface, deposits, which, alter, the, mechanical, properties, of, 'archwires,']), verbo([causing]), complemento([an, increase, in, the, friction, coefficient])]). relacion([sujeto(['Significant']), verbo([increase]), complemento([was, observed, in, the, level, of, debris, '(', 'P', =, 0.0001, ')', ',', surface, roughness, '(', 'P', =, 0.0001, ')', ',', and, friction, resistance, '(', 'P', =, 0.001, ')', of, orthodontic, archwires, after, their, intraoral, exposure])]). relacion([sujeto(['Stainless', steel, test, archwires, showed, a, significant]), verbo([increase]), complemento([in, the, degree, of, debris, and, surface, 'roughness,', increasing, the, frictional, forces, between, the, 'archwire-bracket', interfaces, which, would, considerably, reduce, the, normal, orthodontic, forces])]). relacion([sujeto(['Considering', evaluation, of, 41, studies, in, very, first, 2, years, in, '\'', 'Research', naive, non, academic, institute, demonstrated, successful, implementation, of, trio, model, of, 'Hospital', 'Research', 'Committee', for, administrative, 'review,', 'IEC', for, 'scientific-ethical', 'review,', centralized, 'MRD', for, coordinating, all, research, projects, under, one, roof, which, may]), verbo([act]), complemento([as, role, model, for, 'Research', naive, institutes])]). relacion([sujeto(['Exploring', new, food, items, with, improved, dietary, nutrition, factors, 'may,', 'therefore,', help, to]), verbo([decrease]), complemento([the, mortality, rate, in, the, poor, countries, like, 'Bangladesh'])]). relacion([sujeto([purpureus, could, also]), verbo([act]), complemento([as, a, good, source, of, food, components, essential, for, good, health])]). relacion([sujeto(['The', fatty, acid, 'profile,', 'thus,']), verbo([suggests]), complemento([that, essential, 'omega-6', fatty, acid, linoleic, acid, '(', 'C18:3,', 'ω-6)', and, 'omega-3', linolenic, acid, '(', 'C18:3,', 'ω-3)', were, the, major, polyunsaturated, fatty, acids, '(', 'PUFA)', present, in, 'L'])]). relacion([sujeto(['Finally,', these, results]), verbo([suggest]), complemento([that, 'L'])]). relacion([sujeto(['Up', until, 'now,', few, studies]), verbo([have]), complemento([been, carried, out, to, evaluate, its, effect, as, a, geographical, barrier])]). relacion([sujeto(['Using', mitochondrial, 'DNA', control, region, '(', 'CR)', sequences, and, 13]), verbo([nuclear]), complemento([microsatellite, 'loci,', we, explored, the, genetic, structure, and, gene, flow, in, two, adjacent, tufted, deer, populations, '(', 'Dabashan', and, 'Wulingshan', 'populations),', which, are, separated, by, the, 'Yangtze', 'River'])]). relacion([sujeto(['The', tufted, deer, populations, experienced, population]), verbo([decrease]), complemento([from, 0.3, to, 0.09, 'Ma', 'BP,', then, followed, by, a, distinct, population, increase])]). relacion([sujeto(['The', results, indicated, that, the, 'Yangtze', 'River', may, not]), verbo([act]), complemento([as, an, effective, barrier, to, gene, flow, in, the, tufted, deer])]). relacion([sujeto(['Social', media, can]), verbo([act]), complemento([as, an, important, platform, for, 'debating,', 'discussing,', and, disseminating, information, about, vaccines])]). relacion([sujeto(['The', comments, on, the, 'Facebook', vaccination, opposition, groups, could, be, divided, into, four, 'groups:', comments, with, individualistic, 'perceptions,', comments, that]), verbo([expressed]), complemento([concerns, about, the, safety, of, the, 'OPV,', comments, that, expressed, distrust, in, the, 'Ministry', of, 'Health,', and, comments, denying, 'Polio', as, a, disease])]). relacion([sujeto(['Most', '(', 92, &, 'nbsp;%)', people]), verbo([involved]), complemento([were, parents])]). relacion([sujeto(['The', comments, on, the, social, 'media,', as, well, as, the, 'socio-demographic', profiles, of, the, 'commentators,']), verbo([suggest]), complemento([that, social, media, is, an, active, and, versatile, debate, and, 'discussion-facilitating', platform, in, the, context, of, vaccinations])]). relacion([sujeto(['Health', officials, and, experts, need, to, be, accessible, on, social, 'media,', and, be, equipped, to, readily]), verbo([provide]), complemento([the, 'information,', support, and, advice, the, public, is, looking, for])]). relacion([sujeto(['We']), verbo([found]), complemento([and, 'PCR', validated, one, somatically, acquired, 'tumor-specific', insertion, in, a, case, of, secondary, 'GBM'])]). relacion([sujeto(['However,', several, copies, of, the, element, '(', 11, ')', were]), verbo([found]), complemento([in, genomic, 'DNA', from, blood, and, not, in, the, oncosphere, cultures])]). relacion([sujeto(['SNP', 6.0, microarray, analysis, revealed, deletions, or]), verbo([loss]), complemento([of, heterozygosity, in, the, tumor, genomes, over, the, intervals, corresponding, to, these, 'LINE-1', insertions])]). relacion([sujeto(['These', findings, indicate, that, 'LINE-1', retrotransposon, can]), verbo([act]), complemento([as, an, infrequent, insertional, mutagen, in, secondary, 'GBM,', but, that, retrotransposition, is, uncommon, in, these, central, nervous, system, tumors, as, compared, to, other, neoplasias])]). relacion([sujeto(['A', total, of, 92, differentially]), verbo([expressed]), complemento([proteins, '(', 63, upregulated, proteins, and, 29, downregulated, 'proteins),', which, were, mainly, involved, in, complement, and, coagulation, cascades, and, glucose, metabolism, 'pathway,', were, identified, by, the, proteomic, experiments])]). relacion([sujeto(['Kininogen', 1, '(', 'KNG1)', was, significantly]), verbo([increased]), complemento(['(', p, &, 'lt;', 0.0001, ')', ',', while, apolipoprotein, 'C-III', '(', 'APOC3,', p, &, 'lt;', 0.005, ')', and, paraoxonase, 1, '(', 'PON1,', p, &, 'lt;', 0.001, ')', were, significantly, decreased, in, the, serum, of, 'YDH', syndrome, rats])]). relacion([sujeto(['The', results, indicated, that, 'KNG1,', 'APOC3,', and, 'PON1', may]), verbo([act]), complemento([as, potential, biomarkers, for, diagnosing, 'YDH', syndrome])]). relacion([sujeto(['KNG1', may]), verbo([regulate]), complemento([cytokines, and, chemokines, release, in, 'YDH', 'syndrome,', and, the, low, levels, of, 'PON1', and, 'APOC3', may, increase, oxidative, stress, and, lipolysis, in, 'YDH', 'syndrome,', respectively])]). relacion([sujeto(['Our', work]), verbo([provides]), complemento([a, novel, method, for, 'YDH', syndrome, diagnosis, and, also, provides, valuable, experimental, basis, to, understand, the, molecular, mechanism, of, 'YDH', syndrome])]). relacion([sujeto(['Objective', 'The', basal, ganglia, are, a, group, of, structures, that]), verbo([act]), complemento([as, a, cohesive, functional, unit])]). relacion([sujeto(['He']), verbo([has]), complemento([failed, to, respond, to, drug, 'treatment,', so, he, went, on, rehabilitation, therapy, when, his, problem, progressed])]). relacion([sujeto(['In', this, 'survey,', we, investigate, the, possible]), verbo([causes]), complemento([of, this, type, of, childhood, neurogenic, stuttering])]). relacion([sujeto(['Cerebrospinal', fluid, neuroinflammation, and, 'Alzheimer', disease, '(', 'AD)', biomarkers, may]), verbo([act]), complemento([as, indicators, of, neurodegenerative, disorders, in, diagnostically, unresolved, patients])]). relacion([sujeto(['This', information, is, integral, to]), verbo([ensuring]), complemento([that, patient, information, in, a, variety, of, formats, and, locations, is, properly, secured, and, saved, so, that, it, will, be, available, to, patients, and, caregivers, who, need, it, after, the, facility, closes])]). relacion([sujeto(['This', article, also, goes, into, detail, concerning, some, of, the, financial, tasks]), verbo([required]), complemento([to, be, completed, when, a, facility, closes, because, the, required, data, come, from, coded, information, 'or,', in, the, case, of, the, 'Worker', 'Adjustment', and, 'Retraining', 'Notification', '(', 'WARN)', 'Act,', affect, how, employees, will, be, compensated])]). relacion([sujeto(['This', article]), verbo([provides]), complemento([a, detailed, look, at, the, process, to, help, guide, other, health, information, management, professionals, in, a, diverse, set, of, care, environments, in, the, process, of, facility, closure])]). relacion([sujeto(['Adoption', of, 'Radio-Frequency', 'Identification', '(', 'RFID)', technology]), verbo([has]), complemento([the, ability, to, improve, 'compliance,', reduce, 'costs,', and, improve, safety, in, the, supply, chain, but, its, implementation, has, been, 'limited;', primarily, because, of, hardware, and, tag, costs])]). relacion([sujeto(['The', practical, implication, of, this, study, is, that, pharmaceutical, companies, must, continue, to]), verbo([have]), complemento([the, potential, to, increase, 'revenues,', decrease, associated, 'costs,', and, increase, compliance, with, new, 'FDA', regulations, with, 'RFID'])]). relacion([sujeto(['Still,', challenges, related, to, regulatory, statute, 'wording,', implementation, of, 'two-dimensional', barcode, 'technology,', and, the, variety, of, interfaces, within, the, pharmaceutical, supply, chain]), verbo([have]), complemento([delayed, adoption, and, its, full, implementation])]). relacion([sujeto(['Glioma', patients]), verbo([have]), complemento([a, poor, overall, 'survival;', 'however,', patients, can, show, distinct, clinical, outcomes, due, to, the, high, heterogeneity, of, the, 'tumor,', which, may, be, indicated, by, certain, clinicobiological, parameters])]). relacion([sujeto(['Kinesin', family, member, 20, 'A', '(', 'KIF20A),', which]), verbo([participates]), complemento([in, cytokinesis, and, intracellular, 'transportation,', has, been, recently, reported, to, be, upregulated, in, pancreatic, 'cancer,', breast, 'cancer,', and, bladder, cancer])]). relacion([sujeto(['We']), verbo([found]), complemento([that, 'KIF20A', positive, expression, in, glioma, tissues, correlated, significantly, with, 'Ki67', protein, expression, and, advanced, 'World', 'Health', 'Organization', grade])]). relacion([sujeto(['Univariate', and, multivariate, analysis, revealed, that, 'KIF20A', can]), verbo([act]), complemento([as, an, independent, prognostic, factor, for, predicting, the, overall, survival, of, glioma, patients])]). relacion([sujeto(['Moreover,', we, demonstrated, that, 'KIF20A', can, positively]), verbo([regulate]), complemento([the, expression, of, 'Ki67', in, glioma, cell, lines])]). relacion([sujeto(['Correspondingly,', overexpression, of, 'KIF20A', can]), verbo([promote]), complemento([cell, proliferation, and, 'invasion,', whereas, knockdown, of, 'KIF20A', can, inhibit, cell, viability, and, invasion, capacity])]). relacion([sujeto(['In', vitro, study, also, showed, that, under, the, treatment, of, 'plumbagin,', an, anticancer, 'drug,', 'KIF20A', expression]), verbo([decreased]), complemento([in, a, 'dose-dependent', manner])]). relacion([sujeto(['In', 'addition,', the, overexpression, of, 'KIF20A', can, also]), verbo([increase]), complemento([the, drug, resistance, toward, 'plumbagin,', which, provided, the, possibility, that, 'KIF20A', may, contribute, to, the, chemotherapy, resistance, of, gliomas])]). relacion([sujeto(['The', functions, of, different, 'MLL', proteins]), verbo([have]), complemento([not, been, definitively, studied])]). relacion([sujeto(['MLL1', is, a, histone, methyltransferase, that]), verbo([mediates]), complemento([histone, 'H3', lysine, 4, ',', and, it, has, been, found, to, have, aberrant, expression, in, several, tumors])]). relacion([sujeto(['We']), verbo([report]), complemento([here, that, 'MLL1', is, overexpressed, in, cervical, carcinoma, tissues, and, cell, 'lines,', and, its, overexpression, is, correlated, with, the, tumor, grade])]). relacion([sujeto(['Through', 'FACScan', flow, cytometry, 'assay,', we]), verbo([found]), complemento([that, 'MLL1', promotes, cell, proliferation, by, promoting, the, 'G1/S', transition, through, transcriptional, activation, of, 'CCND1', in, cervical, carcinoma, cells])]). relacion([sujeto(['Furthermore,', we, utilized, 'co-immunoprecipitation', and, glutathione, 'S-transferase', 'pull-down', assays, to, identify, 'β-catenin', as, the, transcription, partner, for, 'MLL1', and, demonstrated, that, 'MLL1', and, 'β-catenin']), verbo([act]), complemento([in, synergy, in, the, transcriptional, activation, of, 'CCND1', in, cervical, carcinoma, cells])]). relacion([sujeto(['In', 'addition,', transwell, assay, and, 'anchorage-independent', cell, growth, assay, also, revealed, that, 'MLL1']), verbo([promotes]), complemento([metastasis, of, cervical, carcinoma, cells, through, interaction, with, 'β-catenin'])]). relacion([sujeto(['In', recent, 'decades,', morbidity, and, mortality]), verbo([have]), complemento([been, found, to, be, significantly, increased, in, patients, with, chronic, obstructive, pulmonary, disease, '(', 'COPD)', complicated, with, pulmonary, tuberculosis, '(', 'PTB)'])]). relacion([sujeto(['This', study, aims, to, investigate, whether, 'PLR', could]), verbo([act]), complemento([as, a, potential, marker, for, patients, with, 'COPD', complicated, with, 'PTB'])]). relacion([sujeto(['Consequently,', it, is, necessary, to]), verbo([have]), complemento([validated, tools, to, measure, changes])]). relacion([sujeto(['This', study]), verbo([has]), complemento([demonstrated, the, validity, of, a, survey, to, evaluate, patient, safety, climate, of, 'Australian', hospital, pharmacy, staff])]). relacion([sujeto(['This', paper, focuses, on, the, role, of, actors, that, operate, outside, formal, health, 'systems,', but, nevertheless]), verbo([have]), complemento([a, 'vital,', if, often, 'under-recognised,', role, in, supporting, public, health])]). relacion([sujeto(['A', method, of, analysis, inspired, by, critical, realism, -, 'Causation', 'Coding', -, enabled, the, identification, of, a, range, of, explanatory, mechanisms, and, potential, pathways, of, causation, between, engagement, in, social, 'enterprise-led', activity, and, various, 'outcomes,', which]), verbo([have]), complemento([been, grouped, into, physical, 'health,', mental, health, and, social, determinants])]). relacion([sujeto(['The', findings, then, informed, the, construction, of, an, 'empirically-informed', conceptual, model, to]), verbo([act]), complemento([as, a, platform, upon, which, to, develop, a, future, research, agenda])]). relacion([sujeto(['The', results, of, this, work, are, considered, to, not, only, encourage, a, broader, and, more, imaginative, consideration, of, what, actually, constitutes, a, public, health, 'intervention,', but, also, reinforces, arguments, that, actors, within, the, 'Third', 'Sector']), verbo([have]), complemento([an, important, role, to, play, in, addressing, contemporary, and, future, public, health, challenges])]). relacion([sujeto(['Guided', tissue, regeneration, '(', 'GTR)']), verbo([has]), complemento([emerged, as, the, most, widely, practiced, regenerative, procedure])]). relacion([sujeto(['Electropsun', mats, were, conducive, to, cellular, attachment, and, viability]), verbo([increased]), complemento([with, time])]). relacion([sujeto(['The', surface, layer, would]), verbo([act]), complemento([as, seal, to, prevent, junctional, epithelium, from, falling, into, the, defect, site, and, hence, maintain, space, for, bone, regeneration])]). relacion([sujeto(['extended-spectrum', cephalosporins, '(', 'ESCs),', fluoroquinolones, '(', 'FQs)', and, 'carbapenems]', among, 'Escherichia', coli, isolates]), verbo([causing]), complemento([clinical, disease, in, 'Australian', 'food-producing', animals])]). relacion([sujeto(['Nevertheless,', the, side, chain, and, the, nature, of, phosphorous, groups, could]), verbo([induce]), complemento([a, poor, aqueous, solubility, and, act, on, their, bioavailability])]). relacion([sujeto(['At', the, same, 'time,', cyclodextrins, are, cage, molecules, that, facilitate, transport, of, hydrophobic, molecules, to]), verbo([enhance]), complemento([the, intestinal, drug, absorption, of, these, molecules, by, forming, inclusion, complexes])]). relacion([sujeto(['The', results, revealed, that, only, the, side, chain, of, bisphosphonate, was]), verbo([involved]), complemento([in, the, inclusion, phenomenon, and, its, length, was, a, crucial, parameter, in, the, control, of, affinity])]). relacion([sujeto(['Findings', from, this, study]), verbo([suggest]), complemento([that, cyclodextrin, will, be, a, useful, carrier, for, bisphosphonates])]). relacion([sujeto(['These', products, are, mostly, are]), verbo([reported]), complemento([in, 'Asia', '(', 44.37, '%', ')', and, 'America', '(', 28.17, '%', ')'])]). relacion([sujeto(['Sixteen', products]), verbo([have]), complemento([their, antifungal, activity, confirmed, by, in, vivo, gold, standard, experimentation])]). relacion([sujeto(['Microbial', natural, 'products,', source, of, 'antifungals,']), verbo([have]), complemento([their, antifungal, mechanism, well, described, in, the, 'literature:', interaction, with, ergosterol, '(', 'polyenes),', inhibition, 1, ',', 3, -, 'β-d-glucan', synthase, '(', 'Echinocandins),', inhibition, of, the, synthesis, of, cell, wall, components, '(', chitin, and, 'mannoproteins),', inhibition, of, sphingolipid, synthesis, '(', serine, 'palmitoyltransferase,', ceramide, 'synthase,', inositol, phosphoceramide, 'synthase)', and, inhibition, of, protein, synthesis, '(', 'sordarins)'])]). relacion([sujeto(['Some', substances, from, arthropods, are, also, explored, to]), verbo([act]), complemento([on, the, fungal, membrane])]). relacion([sujeto(['Interestingly,', synergistic, effects, were]), verbo([found]), complemento([between, different, classes, of, natural, products, as, well, as, between, natural, products, and, azoles])]). relacion([sujeto(['Investigations', must, be, pursued, not, only, to]), verbo([found]), complemento([more, new, 'anti-Candida', compounds, from, plants, and, organisms, but, also, to, carried, out, details, on, molecules, from, already, known, 'anti-Candida', compounds, and, to, more, elucidate, mechanisms, of, action])]). relacion([sujeto(['Amphetamine', and, methamphetamine, use, disorders, are]), verbo([associated]), complemento([with, severe, health, and, social, consequences])]). relacion([sujeto(['No', pharmacological, therapy]), verbo([has]), complemento([been, approved, for, the, treatment, of, these, disorders])]). relacion([sujeto(['Psychostimulants', can]), verbo([act]), complemento([as, 'maintenance-like', therapies, for, managing, substance, use, among, these, patients])]). relacion([sujeto(['The', aim, of, this, study, is, to, evaluate, the, literature, examining, the, efficacy, and, safety, of, psychostimulant, agents, for]), verbo([increasing]), complemento([abstinence, and, treatment, retention, among, patients, with, amphetamine, and, methamphetamine, use, disorders])]). relacion([sujeto(['We', conducted, 'meta-analyses', to]), verbo([provide]), complemento([a, pooled, summary, estimate, for, included, trials, and, report, the, review, according, to, 'PRISMA', guidelines])]). relacion([sujeto(['Outcome']), verbo([reporting]), complemento([across, trials, was, 'inconsistent,', and, the, overall, quality, of, evidence, was, very, low, due, to, high, risk, of, bias, and, indirectness])]). relacion([sujeto(['A', 'meta-analysis', of, five, trials, '(', 642, 'participants)']), verbo([found]), complemento([no, effect, of, psychostimulants, for, 'end-of-study', abstinence, '(', odds, ratio, =, 0.97, ',', 95, '%', confidence, interval, 0.65, to, 1.45, ')'])]). relacion([sujeto(['The', incidence, of, serious, adverse, events, did, not, differ, between, intervention, and, placebo, groups, based, on, qualitative]), verbo([reports]), complemento([from, trials])]). relacion([sujeto(['Cooking', skills, are, increasingly, included, in, strategies, to]), verbo([prevent]), complemento([and, reduce, chronic, 'diet-related', diseases, and, obesity])]). relacion([sujeto(['While', cooking, interventions]), verbo([target]), complemento([all, age, groups, '(', 'Child,', 'Teen', and, 'Adult),', the, optimal, age, for, learning, these, skills, 'on:', 1, ')', skills, 'retention,', 2, ')', cooking, 'practices,', 3, ')', cooking, 'attitudes,', 4, ')', diet, quality, and, 5, ')', health, is, unknown])]). relacion([sujeto(['Similarly,', although, the, source, of, learning, cooking, skills]), verbo([has]), complemento([been, previously, 'studied,', the, differences, in, learning, from, these, different, sources, has, not, been, considered])]). relacion([sujeto(['Mother', remained, the, primary, source, of, 'learning,', 'however,', as, there, is, a]), verbo([reported]), complemento([deskilling, of, domestic, 'cooks,', mothers, may, no, longer, have, the, ability, to, teach, cooking, skills, to, the, next, generation])]). relacion([sujeto(['Resuts', and, 'conclusions:', 'The', factors, used, to, justify, this]), verbo([act]), complemento([are, diverse, and, convert, the, tradition, into, a, form, of, cultural, care])]). relacion([sujeto(['Strips', may, be, constructed, with, a, wide, range, of, compartment, numbers, and, sizes, and, allow, the, researcher, to, house, a, variety, of, genotypes, within, a, single, 'species,', different, 'species,', or, seeds, that]), verbo([have]), complemento([experienced, different, treatments])]). relacion([sujeto(['While', replicate, packets, can, be, included, within, a, 'strip,', different, strips, can]), verbo([act]), complemento([as, blocks, or, can, be, retrieved, at, different, times, for, observation, of, seed, behavior, over, time])]). relacion([sujeto(['Evidence', demonstrates, these, compounds, to, be, capable, of, influencing, the, behaviour, of, 'fish,', but, the, relevance, of, many]), verbo([reported]), complemento([behavioural, endpoints, is, unclear, and, the, value, of, some, findings, has, been, questioned])]). relacion([sujeto(['Since', these, compounds]), verbo([act]), complemento([on, 'neuroendocrine-mediated', pathways, in, 'vertebrates,', the, present, study, explored, how, exposure, to, two, representative, 'SSRIs', '(', fluoxetine, and, 'sertraline)', and, an, 'SNRI', '(', 'venlafaxine)', affect, circadian, rhythms, in, fish])]). relacion([sujeto(['More', 'importantly,', these, findings, may, help]), verbo([reveal]), complemento([why, discrepancies, are, commonly, being, reported, in, the, literature, with, regards, behavioural, effects, in, fish, exposed, to, antidepressants])]). relacion([sujeto(['It', is, thus]), verbo([suggested]), complemento([that, research, be, aimed, at, documenting, behavioural, variability, in, fish, species, used, in, toxicity, 'testing,', to, establish, guidelines, for, quality, control, and, where, possible, inform, the, development, of, standardised, methodologies, so, that, behavioural, analysis, can, be, more, appropriately, applied, to, the, broad, field, of, aquatic, toxicology])]). relacion([sujeto(['As', a, 'result,', investigation, of, 'TLR4', signaling]), verbo([has]), complemento([been, a, major, area, of, research])]). relacion([sujeto(['Despite', this, 'focus,', our, understanding, of, the, mechanisms, that]), verbo([regulate]), complemento(['TLR4', activities, remains, primitive])]). relacion([sujeto(['Nowhere', is, our, knowledge, of, 'TLR4', biology, more, lacking, than, at, the, 'receptor-proximal', 'level,', where, many, factors]), verbo([act]), complemento([in, concert, to, regulate, 'LPS', signaling])]). relacion([sujeto(['Several', recent, studies]), verbo([have]), complemento([begun, filling, these, gaps, in, our, knowledge])]). relacion([sujeto(['In', this, 'review,', we, discuss, the, importance, of, these, receptor, proximal, activities, in, the, spatiotemporal, regulation, of, 'TLR4', 'signaling,', and]), verbo([suggest]), complemento([interesting, areas, for, future, research])]). relacion([sujeto(['In', the, absence, of, congressional, action, to, reinstate, the, federal, ban, on, assault, 'weapons,', tort, litigation, offers, an, alternative, strategy, for]), verbo([regulating]), complemento([what, have, become, the, weapons, of, choice, in, mass, shootings])]). relacion([sujeto(['Enigmatic', lipid, peroxidation, products]), verbo([have]), complemento([been, claimed, as, the, proximate, executioners, of, 'ferroptosis-a', specialized, death, program, triggered, by, insufficiency, of, glutathione, peroxidase, 4, '(', 'GPX4)'])]). relacion([sujeto(['Using', quantitative, redox, 'lipidomics,', reverse, 'genetics,', bioinformatics, and, systems, 'biology,', we, discovered, that, ferroptosis]), verbo([involves]), complemento([a, highly, organized, oxygenation, 'center,', wherein, oxidation, in, 'endoplasmic-reticulum-associated', compartments, occurs, on, only, one, class, of, phospholipids, '(', phosphatidylethanolamines, '(', 'PEs))', and, is, specific, toward, two, fatty, 'acyls-arachidonoyl', '(', 'AA)', and, adrenoyl, '(', 'AdA)'])]). relacion([sujeto(['Suppression', of, 'AA', or, 'AdA', esterification, into, 'PE', by, genetic, or, pharmacological, inhibition, of, 'acyl-CoA', synthase, 4, '(', 'ACSL4)']), verbo([acts]), complemento([as, a, specific, antiferroptotic, rescue, pathway])]). relacion([sujeto(['Lipoxygenase', '(', 'LOX)', generates, doubly, and, 'triply-oxygenated', '(', 15, -, 'hydroperoxy)-diacylated', 'PE', 'species,', which]), verbo([act]), complemento([as, death, 'signals,', and, tocopherols, and, tocotrienols, '(', vitamin, 'E)', suppress, 'LOX', and, protect, against, 'ferroptosis,', suggesting, a, homeostatic, physiological, role, for, vitamin, 'E'])]). relacion([sujeto(['This', oxidative, 'PE', death, pathway, may, also, represent, a]), verbo([target]), complemento([for, drug, discovery])]). relacion([sujeto(['We', projected, that, 90, ',', 0, people]), verbo([have]), complemento([lost, 'PLYs', due, to, back, problems, in, 2015, ',', increasing, to, 104, ',', 600, in, 2030, '(', 16.2, '%', 'increase)'])]). relacion([sujeto(['National', costs, consisted, of, a]), verbo([loss]), complemento([of, 'AU$2931', million, in, annual, income, in, 2015, ',', increasing, to, 'AU$4660', million, in, 2030, '(', 60, '%', 'increase)'])]). relacion([sujeto(['For', 'government,', extra, annual, welfare, payments, are, projected, to]), verbo([increase]), complemento([from, 'AU$1462', million, in, 2015, to, 'AU$1709', million, in, 2030, '(', 16.9, '%', 'increase),', and, lost, annual, taxation, revenue, to, increase, from, 'AU$671', million, in, 2015, to, '$961', million, in, 2030, '(', 43.2, '%', 'increase)'])]). relacion([sujeto(['We', projected]), verbo([losses]), complemento([in, 'GDP', of, 'AU$10,543', million, in, 2015, ',', increasing, to, 'AU$14,522', million, in, 2030, due, to, back, problems])]). relacion([sujeto(['Most', private, health, insurance, was]), verbo([associated]), complemento([with, 'employment,', and, job, loss, meant, insurance, loss])]). relacion([sujeto(['Recent']), verbo([reports]), complemento([indicate, that, 'NK', cells, are, activated, in, response, to, allergens, in, vivo])]). relacion([sujeto(['NK', cells]), verbo([promote]), complemento([allergic, 'sensitization,', 'type-2', immune, 'response,', development, of, eosinophilic, 'inflammation,', and, airway, hyperresponsiveness])]). relacion([sujeto(['NK', cells, are]), verbo([activated]), complemento([by, respiratory, syncytial, virus, and, other, respiratory, viruses])]). relacion([sujeto(['Prenatally', programmed, 'NK', cells, produce, 'type-2', and, 'type-3', cytokines, and]), verbo([mediate]), complemento([asthma, predisposition])]). relacion([sujeto(['NK', cells, can, also]), verbo([act]), complemento([as, asthma, antagonists])]). relacion([sujeto(['When', viral, infection, occurs, in, naïve, mice, prior, to, allergic, 'sensitization,', 'NK', cells, antagonize, 'type-2', immunity, and]), verbo([prevent]), complemento([development, of, asthma])]). relacion([sujeto(['The', environmental, context, determines, whether, 'NK', cells]), verbo([act]), complemento([as, protagonists, or, antagonists])]). relacion([sujeto(['Categorization']), verbo([has]), complemento([been, associated, with, distributed, networks, of, the, primate, 'brain,', including, the, prefrontal, cortex, '(', 'PFC)', and, posterior, parietal, cortex, '(', 'PPC)'])]). relacion([sujeto(['Although', 'category-selective', spiking, in, 'PFC', and, 'PPC']), verbo([has]), complemento([been, 'established,', the, 'frequency-dependent', dynamic, interactions, of, frontoparietal, networks, are, largely, unexplored])]). relacion([sujeto(['We']), verbo([found]), complemento(['category-selective', 'beta-', and, 'delta-band', synchrony, between, and, within, the, areas])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, 'long-range', 'beta-band', synchrony, could, act, as, a, filter, that, only, supports, neural, representations, of, the, variables, relevant, to, the, task, at, hand])]). relacion([sujeto(['It']), verbo([has]), complemento([been, observed, that, the, bond, orientational, ordering, rather, than, the, translational, ordering, '(', 'density)', plays, a, primary, role])]). relacion([sujeto(['Under', the, conditions, of, small, 'supercooling,', the, system, is, likely, to, be, nucleated, into, crystals, that]), verbo([have]), complemento([a, preference, for, the, metastable, bcc, 'structure,', which, can, be, regarded, as, a, manifestation, of, the, 'Alexander-McTague', mechanism])]). relacion([sujeto(['In', 'contrast,', small, nuclei, are]), verbo([found]), complemento([to, have, a, preference, for, fcc, symmetry, under, conditions, of, a, high, degree, of, supercooling])]). relacion([sujeto(['Prestructured', precursors, that]), verbo([act]), complemento([as, seeds, and, wet, on, the, nuclei, during, nucleation, always, have, a, high, degree, of, 'bcc-like', 'ordering,', despite, different, state, points])]). relacion([sujeto(['The', results, above, may]), verbo([provide]), complemento([a, clue, to, the, understanding, of, the, crystallization, process, in, 'core-softened', particles])]). relacion([sujeto(['Thus,', rapid, and, accurate, identification, of, clinical, 'Candida', isolates, is, fundamental, in]), verbo([ensuring]), complemento([timely, and, effective, treatments, are, delivered])]). relacion([sujeto(['Rapid', 'Evaporative', 'Ionisation', 'Mass', 'Spectrometry', '(', 'REIMS)']), verbo([has]), complemento([previously, been, shown, to, provide, a, 'high-throughput', platform, for, the, rapid, and, accurate, identification, of, bacterial, and, fungal, isolates])]). relacion([sujeto(['In', comparison, to, commercially, available, matrix, assisted, laser, desorption, ionisation, time, of, flight, mass, spectrometry, '(', 'MALDI-ToF),', 'REIMS', based, methods]), verbo([require]), complemento([no, preparative, steps, nor, 'time-consuming', cell, extractions])]). relacion([sujeto(['Here,', we]), verbo([report]), complemento([on, the, ability, of, 'REIMS-based', analysis, to, rapidly, and, accurately, identify, 153, clinical, 'Candida', isolates, to, species, level])]). relacion([sujeto(['In', 'addition,', significantly, different, '(', 'FDR', corrected, 'P', value, &, 'lt;', 0.05, ')', lipids, within, the, 600, to, 1000, 'm/z', mass, range, were, 'identified,', which, could]), verbo([act]), complemento([as, 'species-specific', biomarkers, in, complex, microbial, communities])]). relacion([sujeto(['Lead-free', relaxor, ferroelectrics, that, feature, a, 'core-shell', microstructure]), verbo([provide]), complemento([an, excellent, electromechanical, response])]). relacion([sujeto(['They', even]), verbo([have]), complemento([the, potential, to, replace, the, environmentally, hazardous, 'lead-zirconia-titanate', '(', 'PZT)', in, large, strain, actuation, applications])]). relacion([sujeto(['Although', the, dielectric, properties, of, 'core-shell', ceramics]), verbo([have]), complemento([been, extensively, 'investigated,', their, piezoelectric, properties, are, not, yet, well, understood])]). relacion([sujeto(['We']), verbo([found]), complemento([that, after, 'poling,', lateral, domains, emerged, at, the, 'core-shell', interface, and, propagated, to, the, shell, region])]). relacion([sujeto(['Phase', field, simulations, showed, that, the]), verbo([increased]), complemento([electrical, potential, beneath, the, core, is, responsible, for, the, 'in-plane', domain, evolution])]). relacion([sujeto(['Our', results, imply, that, the, 'field-induced', domains]), verbo([act]), complemento([as, pivotal, points, at, the, coherent, heterophase, 'core-shell', 'interface,', reinforcing, the, phase, transition, in, the, 'non-polar', shell, and, thus, promoting, the, giant, strain])]). relacion([sujeto(['Valsalva', maneuver, is]), verbo([associated]), complemento([with, diverse, physiological, changes])]). relacion([sujeto(['Valsalva', maneuver, is, also, employed, during, various, phases, of, neurosurgical, procedures, to, achieve, specific]), verbo([targets]), complemento([and, confirm, intraoperative, findings])]). relacion([sujeto(['The']), verbo([associated]), complemento([complications, of, this, act, have, also, been, discussed])]). relacion([sujeto(['This', is, the, official, guideline, endorsed, by, the, specialty, associations]), verbo([involved]), complemento([in, the, care, of, head, and, neck, cancer, patients, in, the, 'UK'])]). relacion([sujeto(['It', discusses, the, role, of, the, clinical, nurse, specialist, in, the, head, and, neck, cancer, patient, journey, and]), verbo([provides]), complemento([recommendations, on, the, clinical, nurse, specialist, led, assessments, and, interventions, for, this, group, of, patients, receiving, cancer, care])]). relacion([sujeto(['(', 'R)', '•', 'Clinical', nurse, specialists, must]), verbo([act]), complemento([as, gate, keeper, to, the, 'patients\'', cancer, pathway, to, provide, a, seamless, journey])]). relacion([sujeto(['(', 'G)', '•', 'Clinical', nurse, specialists, should]), verbo([lead]), complemento([in, redesigning, of, services, and, policies, to, ensure, they, are, responsive, to, 'patient\'s', needs, for, the, future])]). relacion([sujeto(['(', 'G)', '•', 'Treatment', summaries, should, become, part, of, practice, to]), verbo([provide]), complemento([good, communication, between, primary, and, secondary, care, to, enable, continuity, of, care, for, the, patient])]). relacion([sujeto(['These', health, information, systems, '(', 'HIS)', typify, systems, in, that, they]), verbo([have]), complemento([multiple, interacting, 'components,', and, they, are, embedded, within, larger, systems])]). relacion([sujeto(['Components', of, a, larger, system]), verbo([act]), complemento([as, the, context, for, all, 'lower-level', systems])]). relacion([sujeto(['We']), verbo([provide]), complemento([examples, of, each, as, experienced, by, those, working, to, strengthen, 'HIS', in, 'LMICs'])]). relacion([sujeto(['Professional', isolation, and, attitudinal, barriers, from, colleagues, were, seen, to]), verbo([inhibit]), complemento([the, effectiveness, of, lived, experience, roles])]). relacion([sujeto(['Lived', experience, practitioners, can]), verbo([provide]), complemento([a, vital, contribution, to, stigma, reduction, 'broadly,', 'however,', the, stigma, and, discrimination, they, face, within, work, roles, must, be, addressed, to, allow, this, contribution, to, be, effective])]). relacion([sujeto(['For', more, than, a, 'decade,', the, 'SNaPshot(®)', technique]), verbo([has]), complemento([been, utilised, to, analyse, identity, and, 'FDP-associated', 'SNPs', in, forensic, 'DNA', analysis])]). relacion([sujeto(['Analgesic', strategy, of, a, single, drug, analgesia, in, bone, cancer, pain, '(', 'BCP)']), verbo([has]), complemento([shifted, to, combined, analgesia, with, different, drugs, which, have, different, mechanism])]). relacion([sujeto(['After', tumor, cell, 'inculation,', the, activation, of, signal, transducer, and, activator, of, transcription, '(', 'STAT3)', and, extracellular, 'signal-regulated', kinase, '(', 'ERK)', signaling, pathway, are]), verbo([involved]), complemento([in, the, development, and, maintenance, of, 'BCP,', whereas, a, decrease, in, the, expression, of, spinal, 'STAT3', and, 'ERK', through, using, their, specific, 'blocker,', lead, to, attenuation, of, 'BCP'])]). relacion([sujeto([')', injection, of, midazolam, '(', 'MZL)', and, ropivacaine, '(', 'Ropi)']), verbo([induces]), complemento([synergistic, analgesia, on, 'BCP', and, is, accompanied, with, different, mechanisms, of, these, analgesic, effect])]). relacion([sujeto(['At', consecutive, daily, administration, 'experiment,', thermal, hyperalgesia, was, 'recorded,', and, immunohistochemical, staining, was, used, to, detect, the, expression, of, 'c-Fos,', spinal, glial, fibrillary, acidic, protein, '(', 'GFAP)', and, ionized, calcium]), verbo([binding]), complemento([adapter, 'molecule-1', '(', 'IBA-1)'])]). relacion([sujeto([&, 'nbsp;MZL', or, 'Ropi', showed, a, 'short-term', analgesia, 'dose-dependently,', and, 'MZL', displayed, better, effect, on, inhibition, of, pSTAT3, expression, than, 'pERK,', but, 'Ropi', was, just, the, 'reverse,', then, consecutive, daily, administrations, of, their, combination]), verbo([acted]), complemento([synergistically, to, attenuate, thermal, hyperalgesia, with, downregulated, spinal, '\'', 'neuron-astrocytic', 'activation\'', in, the, 'BCP', rats])]). relacion([sujeto(['Spinal', different, signaling, pathway, inhibition, for, 'MZL', and, 'Ropi', may, be]), verbo([involved]), complemento([in, this, process])]). relacion([sujeto(['It', is]), verbo([found]), complemento([that, 'pyrrhotite-11T', iron, sulfide, '(', 'Fe-S)', 'NPs', with, an, average, size, of, '≈15', nm, are, encapsulated, in, the, tubular, cavity, of, the, 'CNTs', '(', 'Fe-S@CNTs),', and, each, particle, is, a, single, crystal])]). relacion([sujeto(['In', situ, transmission, electron, microscopy, studies, show, that, the, 'CNTs', not, only, play, an, essential, role, in, accommodating, the, volume, expansion, of, the, 'Fe-S', 'NPs', but, also]), verbo([provide]), complemento([a, fast, transport, path, for, 'Li', ions])]). relacion([sujeto(['The', results, demonstrate, that, 'CNTs']), verbo([act]), complemento([as, a, unique, nanocontainer, and, reactor, that, permit, the, loading, and, formation, of, electrochemically, active, materials, with, desirable, electrochemical, lithium, storage, performance])]). relacion([sujeto(['Poly(amidoamine)', '(', 'PAMAM)', is, conjugated, into, 'THS', to]), verbo([act]), complemento([as, an, anchor, for, small, interfering, 'RNA', '(', 'siRNA),', allowing, to, load, the, 'THS', with, therapeutic, payload])]). relacion([sujeto(['By', modification, of, the, protein, cage, with, the, 'cell-penetrating', peptide, 'TAT,', 'RNA', interference, is, also]), verbo([induced]), complemento([in, 'PC-3', cells])]). relacion([sujeto(['The', decomposition, of, 'chloro-form', in, the, presence, of, oxygen, and, moisture]), verbo([provides]), complemento(['HCl,', which, leads, to, the, breakdown, of, nanojars, to, the, title, trinuclear, 'copper(II)', pyrazolate, 'complex,', and, possibly, 'Cu(II)', ions, and, free, 4, -, 'iodo-pyrazole'])]). relacion([sujeto(['Cu(II)', 'ions,', in, 'turn,']), verbo([act]), complemento([as, catalyst, for, the, accelerated, decomposition, of, 'chloro-form,', ultimately, leading, to, the, complete, breakdown, of, nanojars])]). relacion([sujeto(['The', crystal, structure, presented, here]), verbo([provides]), complemento([the, first, structural, description, of, a, trinuclear, 'copper(II)', pyrazolate, complex, with, 'iodine-substituted', pyrazoles])]). relacion([sujeto(['This', difference, is, likely, a, result, of, the, presence, of, the, iodine, 'substituent,', which]), verbo([provides]), complemento([a, 'unique,', novel, feature, in, copper, pyrazolate, chemistry])]). relacion([sujeto(['Thus,', the, iodine, atoms, form, halogen, bonds, with, the, terminal, chlorido, ligands, of, the, surrounding, complexes, '[', mean, length, of, 'I⋯Cl', contacts, =, 3.48, '(', 1, ')', 'Å],']), verbo([leading]), complemento([to, an, extended, 'two-dimensional,', 'halogen-bonded', network, along, '(', -, 110, ')'])]). relacion([sujeto(['The', cavities, within, this, framework, are, filled, by, centrosymmetric, 1, ',', 4, -, dioxane, solvent, 'mol-ecules,', which, create, further, bridges, via, 'C-H⋯Cl', hydrogen, bonds, with, terminal, chlorido, ligands, of, the, trinuclear, complex, not]), verbo([involved]), complemento([in, halogen, bonding])]). relacion([sujeto(['An', immersed, 'boundary-lattice', 'Boltzmann', method, is, developed, for, 'fluid-structure', interactions]), verbo([involving]), complemento(['non-Newtonian', fluids, '(', e])]). relacion([sujeto(['It', is]), verbo([found]), complemento([that, the, deformation, of, the, capsule, increases, with, the, 'power-law', index, for, different, 'Reynolds', numbers, and, nondimensional, shear, rates])]). relacion([sujeto(['In', 'addition,', the, 'Reynolds', number, does, not]), verbo([have]), complemento([significant, effect, on, the, capsule, deformation, in, the, flow, regime, considered])]). relacion([sujeto(['Microglia', activation, is, a, neuroinflammatory, response, to, parenchymal, damage, with]), verbo([release]), complemento([of, intracellular, 'metabolites,', e])]). relacion([sujeto(['Extracellular', purines, can, elicit, 'Ca(2+)-mediated', microglia, activation]), verbo([involving]), complemento(['P2X/P2Y', receptors, with, metabotropic, '(', 'P2Y)', and, ionotropic, '(', 'P2X)', cell, signaling, in, target, cells])]). relacion([sujeto(['Such', microglia, activation, results, in]), verbo([increased]), complemento([phagocytic, 'activity,', activation, of, their, inflammasome, and, release, of, cytokines, to, sustain, neuroinflammatory, '(', 'so-called', 'M1/M2', 'polarization)'])]). relacion([sujeto(['ATP-induced', activation, of, ionotropic, 'P2X4', and, 'P2X7', receptors, differentially]), verbo([induces]), complemento(['receptor-operated', 'Ca(2+)', entry, '(', 'ROCE)'])]). relacion([sujeto(['Although', 'store-operated', 'Ca(2+)', entry, '(', 'SOCE)', was, identified, to]), verbo([modulate]), complemento(['ROCE', in, primary, 'microglia,', its, existence, and, role, in, one, of, the, most, common, murine, microglia, cell, 'line,', 'BV2,', is, unknown])]). relacion([sujeto(['High', 'ATP', concentrations, '(', 1, 'mM)', elicited, sustained]), verbo([increases]), complemento([in, intracellular, '[', 'Ca(2+)]i', whereas, lower, concentrations, '(', '≤100', 'μM)', also, induced, 'Ca(2+)', oscillations])]). relacion([sujeto(['Pharmacologically']), verbo([inhibiting]), complemento(['P2Y', and, 'P2X', responses, did, not, affect, 'SOCE,', and, in, 'fact,', 'P2Y-responses', were, barely, detectable, in, 'BV2', cells])]). relacion([sujeto(['Using', automated, classifier, 'analysis,', several, drugs, '(', 'minocycline,', 'U73122,', 'U73343,', 'wortmannin,', 'LY294002,', 'AZ10606120)', were, tested, on, their, profile, to]), verbo([act]), complemento([on, 'Ca(2+)', oscillations, '(', 'P2X4)', and, sustained, '[', 'Ca(2+)]i', increases])]). relacion([sujeto(['We', demonstrate, specific, drug, effects, on, purinergic, 'Ca(2+)', pathways, and]), verbo([provide]), complemento([new, pharmacological, insights, into, 'Ca(2+)', oscillations, in, 'BV2', cells])]). relacion([sujeto(['For', 'example,', minocycline]), verbo([inhibits]), complemento([both, 'P2X7-', and, 'P2X4-mediated', 'Ca(2+)-responses,', and, this, may, explain, its, 'anti-inflammatory', action, in, neuroinflammatory, disease])]). relacion([sujeto(['As', a, technical, 'result,', our, novel, automated, 'bio-screening', approach]), verbo([provides]), complemento([a, biomedical, engineering, platform, to, allow, 'high-content', drug, library, screens, to, study, 'neuro-inflammation', in, vitro])]). relacion([sujeto(['Monounsaturated', fat, consumption]), verbo([has]), complemento([been, considered, to, decrease, 'low-density', lipoprotein, '(', 'LDL)', cholesterol])]). relacion([sujeto(['Linoleic', acid, lipid, radicals, can, also, be, used, to]), verbo([act]), complemento([as, an, antioxidant, agent, in, natural, phenols])]). relacion([sujeto(['Palmitoleic', acid, is, a, beneficial, fatty, acid, not, only, to]), verbo([increase]), complemento([insulin, sensitivity, by, suppressing, 'inflammation,', but, also, to, inhibit, the, destruction, of, 'insulin-secreting', pancreatic, beta, cells])]). relacion([sujeto(['This', could, be, due, to, differences]), verbo([associated]), complemento([with, the, environment, and, cultivation, of, the, plants])]). relacion([sujeto(['As', 'English', social, care, services, reconstruct, themselves, in, response, to, the, personalization, 'agenda,', there, is]), verbo([increased]), complemento([interest, in, the, contribution, of, 'micro-providers', -, very, small, 'community-based', 'organizations,', which, can, work, directly, with, individuals])]). relacion([sujeto(['These', 'micro-providers', are, assumed, to, be, able, to, cater, for, the, '\'', seldom, 'heard\'', groups, which]), verbo([have]), complemento([been, marginalized, within, mainstream, social, care, services])]). relacion([sujeto(['It', considers, the, marginalising, dynamics, in, 'mainstream,', statutory, social, care, support, 'provision,', and, how, far, local, 'community,', specialist, or, 'small-scale', services, are]), verbo([responding]), complemento([to, unmet, need, for, support, and, advice, among, marginalized, groups])]). relacion([sujeto(['The', review]), verbo([found]), complemento([that, there, is, a, tradition, of, compensatory, 'self-organization,', use, of, informal, networks, and, a, mobilization, of, social, capital, for, all, these, groups, in, response, to, marginalization, from, 'mainstream,', statutory, services])]). relacion([sujeto(['This']), verbo([requires]), complemento([recognition, and, nurturing, in, ways, that, do, not, stifle, its, unique, nature])]). relacion([sujeto(['Oblongifolin', 'C', '(', 'OC)', and, guttiferone, 'K', '(', 'GUTK)', are, two, anticancer, compounds, extracted, from, 'Garcinia', yunnanensis, 'Hu,', but, they]), verbo([act]), complemento([by, different, mechanisms])]). relacion([sujeto(['Compared', to, 'OC', and, 'GUTK', 'alone,', the, combination, of, 'OC', and, 'GUTK', as, well, as, the, ethanol, extracts, more, potently]), verbo([inhibited]), complemento([the, cancer, cell, growth, with, 'IC50', values, of, 3.4, 'μmol/L', and, 3.85, 'μg/mL,', respectively])]). relacion([sujeto(['Furthermore,', 'OC', and, 'GUTK', displayed, synergistic, inhibition, on, 'HCT116', 'cells:', 'co-treatment', with, 'OC', and, 'GUTK']), verbo([induced]), complemento([more, prominent, apoptosis, than, treatment, with, either, drug, alone])]). relacion([sujeto(['Moreover,', the, combination, of, 'OC', and, 'GUTK', markedly]), verbo([increased]), complemento([cleavage, of, 'casapse-3', and, 'PARP,', and, enhanced, cellular, 'ROS', production, and, increased, 'JNK', protein, phosphorylation])]). relacion([sujeto(['In', 'addition,', the, combination, of, 'OC', and, 'GUTK', exerted, stronger, effects, under, 'nutrient-deprived', conditions, than, in, complete, 'medium,']), verbo([suggesting]), complemento([that, autophagy, played, an, essential, role, in, regulating, 'OC-', and, 'GUTK-mediated', cell, death])]). relacion([sujeto(['OC', and, 'GUTK', are, the, main, components, that, contribute, to, the, anticancer, activity, of, 'G', yunnanensis, and, the, compounds]), verbo([have]), complemento(['apoptosis-inducing', effects, in, 'HCT116', cells, in, vitro])]). relacion([sujeto(['Based', on, our, 'results,', 'VaFKBP22', appears, to]), verbo([act]), complemento([as, cochaperone, of, 'VaDnaK,', and, contribute, to, protein, folding, and, stabilization, via, its, 'peptidyl-prolyl', 'cis/trans', isomerization, activity])]). relacion([sujeto(['Proton', pump, inhibitors, '(', 'PPIs)', were, clinically, introduced, more, than, 25, years, ago, and]), verbo([have]), complemento([since, proven, to, be, 'invaluable,', 'safe,', and, effective, agents, for, the, management, of, a, variety, of, 'acid-related', disorders])]). relacion([sujeto(['Although', all, members, in, this, class]), verbo([act]), complemento([in, a, similar, 'fashion,', inhibiting, active, parietal, cell, acid, 'secretion,', there, are, slight, differences, among, 'PPIs', relating, to, their, pharmacokinetic, 'properties,', 'metabolism,', and, 'Food', and, 'Drug', 'Administration', '(', 'FDA)-approved', clinical, indications])]). relacion([sujeto(['Despite', their, overall, 'efficacy,', 'PPIs', do]), verbo([have]), complemento([some, limitations, related, to, their, short, plasma, 'half-lives', and, requirement, for, 'meal-associated', 'dosing,', which, can, lead, to, breakthrough, symptoms, in, some, 'individuals,', especially, at, night])]). relacion([sujeto(['Longeracting', 'PPIs', and, technology, to, prolong, conventional, 'PPI', activity]), verbo([have]), complemento([been, developed, to, specifically, address, these, limitations, and, may, improve, clinical, outcomes])]). relacion([sujeto(['Some', efforts]), verbo([have]), complemento([been, made, to, show, the, reliability, and, performance, of, the, present, method, compared, with, the, numerical, 'method,', 'Runge-Kutta', 'fourth-order'])]). relacion([sujeto(['The', results]), verbo([reveal]), complemento([that, the, 'HPM', can, achieve, suitable, results, in, predicting, the, solution, of, these, problems])]). relacion([sujeto(['The', results]), verbo([reveal]), complemento([that, the, increase, in, the, pressure, gradient, and, 'Thermophoresis', parameter, as, well, as, decrease, in, the, 'Brownian', motion, parameter, cause, the, rise, in, the, velocity, profile])]). relacion([sujeto(['Furthermore,', either]), verbo([increase]), complemento([in, 'Thermophoresis', or, decrease, in, 'Brownian', motion, parameters, results, in, enhancement, in, nanoparticle, concentration])]). relacion([sujeto(['Liposomes']), verbo([have]), complemento([been, the, centre, of, attention, in, research, due, to, their, potential, to, act, as, drug, delivery, systems])]). relacion([sujeto(['Liposomes', characterisation, was, evaluated, through, stability, 'studies,', encapsulation, efficacy, and, drug]), verbo([release]), complemento([profiles, of, hydrophilic, and, lipophilic, compounds])]). relacion([sujeto(['One', hydrophilic, and, one, lipophilic, compounds, were, incorporated, showing, how, formulation, and, 'physic-chemical', characteristics, can, influence, the, drug]), verbo([release]), complemento([profile])]). relacion([sujeto(['The', three, treatment, groups, were, assumed, to]), verbo([have]), complemento([equivalent, efficacy, above, 90, '%'])]). relacion([sujeto(['The', most, common, adverse, events]), verbo([reported]), complemento([in, the, 're-treatment', 'ACT', group, were, anorexia, '(', 31, '[', 13, '%', ']', of, 240, 'patients),', asthenia, '(', 20, '[', 8, '%', ']', ')', ',', coughing, '(', 16, '[', 7, '%', ']', ')', ',', abnormal, behaviour, '(', 13, '[', 5, '%', ']', ')', ',', and, diarrhoea, '(', 12, '[', 5, '%', ']', ')'])]). relacion([sujeto(['Anorexia', '(', 13, '[', 6, '%', ']', of, 233, 'patients)', was, the, most, frequently]), verbo([reported]), complemento([adverse, event, in, the, alternative, 'ACT', group])]). relacion([sujeto(['The', most, commonly]), verbo([reported]), complemento([adverse, events, in, the, 'QnC', group, were, anorexia, '(', 12, '[', 12, '%', ']', of, 98, 'patients),', abnormal, behaviour, '(', 6, '[', 6, '%', ']', ')', ',', asthenia, '(', 6, '[', 6, '%', ']', ')', ',', and, pruritus, '(', 5, '[', 5, '%', ']', ')'])]). relacion([sujeto(['However,', the, effect, of, this, approach, on, the, selection, of, resistant, strains, should, be, monitored, to]), verbo([ensure]), complemento([that, 're-treatment', with, the, same, 'ACT', does, not, contribute, to, 'P', falciparum, resistance])]). relacion([sujeto(['Creatine', '(', 'Cr)', is, an, important, organic, compound]), verbo([acting]), complemento([as, intracellular, 'high-energy', phosphate, shuttle, and, in, energy, storage])]). relacion([sujeto(['While', located, in, most, cells, where, it, plays, its, main, roles, in, energy, metabolism, and, 'cytoprotection,', 'Cr', is, highly, concentrated, in, muscle, and, brain, 'tissues,', in, which, 'Cr', also, appears, to]), verbo([act]), complemento([in, osmoregulation, and, neurotransmission])]). relacion([sujeto(['PVP', can]), verbo([act]), complemento([as, a, capping, and, etching, agent, for, protection, of, the, outer, surface, nanoparticles, and, formation, of, a, mesoporous, 'shell,', respectively])]). relacion([sujeto(['Another', important, feature, of, this, work, is, the, choice, of, the, ligand, '(', 1, ',', 10, -, 'phenanthroline)', for, precursor, cadmium, complex, that, works, as, a, chelating, agent, in, order, to]), verbo([increase]), complemento([optical, and, electrical, properties, and, stability, of, prepared, nanomaterial])]). relacion([sujeto(['The', nanoparticles]), verbo([have]), complemento([been, characterized, by, field, emission, scanning, electron, microscopy, '(', 'FESEM),', transmission, electron, microscope, '(', 'TEM),', energy, dispersive, 'X-ray', spectroscopy, '(', 'EDX),', 'X-ray', diffraction, '(', 'XRD),', 'UV-vis,', photoluminescence, '(', 'PL)', 'spectroscopy,', 'FT-IR,', and, cyclic, voltammetry, techniques])]). relacion([sujeto(['The', 'PL', spectroscopy, study, of, 'CoFe2O4@CdSe']), verbo([has]), complemento([shown, significant, 'PL', quenching, by, the, formation, of, 'CoFe2O4', core, inside, 'CdSe,', this, shows, that, 'CoFe2O4', 'NPs', are, efficient, electron, acceptors, with, the, 'CdSe'])]). relacion([sujeto(['It', is, clearly, observed, that, the, biosensor, can, significantly]), verbo([enhance]), complemento([electrocatalytic, activity, towards, the, oxidation, of, 'RIF,', under, the, optimal, conditions])]). relacion([sujeto(['Although', 'genome-scale', maps, of, introgressed, sequences]), verbo([have]), complemento([been, constructed, '[', 3, -, 6, ']', ',', considerable, gaps, in, knowledge, remain, about, the, 'functional,', 'phenotypic,', and, evolutionary, significance, of, archaic, hominin, 'DNA', that, persists, in, 'present-day', individuals])]). relacion([sujeto(['Here,', we, describe, a, comprehensive, set, of, analyses, that, identified, 126, 'high-frequency', archaic, haplotypes, as, putative]), verbo([targets]), complemento([of, adaptive, introgression, in, geographically, diverse, populations])]). relacion([sujeto(['Furthermore,', we, leveraged, existing, and, novel, 'large-scale', gene, expression, datasets, to, show, many, positively, selected, archaic, haplotypes]), verbo([act]), complemento([as, expression, quantitative, trait, loci, '(', 'eQTLs),', suggesting, that, modulation, of, transcript, abundance, was, a, common, 'mechanism facilitating', adaptive, introgression])]). relacion([sujeto(['Our', results, demonstrate, that, hybridization, between, modern, and, archaic, hominins]), verbo([provided]), complemento([an, important, reservoir, of, advantageous, alleles, that, enabled, adaptation, to, 'out-of-Africa', environments])]). relacion([sujeto(['Here,', we]), verbo([report]), complemento([the, crystal, structure, of, the, 'Rasip1', 'RA', domain, '(', 'RRA)', 'alone,', revealing, the, basis, of, 'dimerization,', and, in, complex, with, 'Rap1', at, 2.8, &, 'nbsp;Å', resolution])]). relacion([sujeto(['In', contrast, to, most, 'RA', 'domains,', 'RRA', formed, a, dimer, that, can]), verbo([bind]), complemento([two, 'Rap1', '(', 'KD =', 0.9, &, 'nbsp;μM)', or, 'Ras', '(', 'KD =', 2.2, &, 'nbsp;μM)', molecules])]). relacion([sujeto(['We', solved, the, 'Rap1-RRA', complex, and]), verbo([found]), complemento([that, 'Rasip1', binds, 'Rap1', in, the, 'Switch', 'I', 'region,', and, 'Rap1', binding, induces, few, conformation, changes, to, 'Rasip1', stabilizing, a, β, strand, and, an, unstructured, loop])]). relacion([sujeto(['Our', data, explain, how, 'Rasip1', can]), verbo([act]), complemento([as, a, 'Rap1', and, 'Ras', effector, and, show, that, 'Rasip1', defines, a, subgroup, of, dimeric, 'RA', domains, that, could, mediate, cooperative, binding, to, 'membrane-associated', 'Ras', superfamily, members])]). relacion([sujeto(['We']), verbo([find]), complemento([that, both, income, and, time, scarcity, reduce, physical, activity, 'and,', in, some, 'cases,', lead, people, to, consume, less, fruit, and, 'vegetables,', eat, out, more, and, eat, more, discretionary, calories, '(', food, high, in, 'salt,', sugar, or, 'fat)'])]). relacion([sujeto(['Further,', income, and, time, scarcity, operate, independently, to, constrain, healthy, 'choices,', although, for, more, than, one, in, ten, people, they, synergistically]), verbo([increase]), complemento([risk])]). relacion([sujeto(['The', evolutionary, transition, from, an, 'ape-like', to, 'human-like', upper, extremity, occurred, in, the, context, of, a, behavioral, shift, from, an, upper, limb, predominantly]), verbo([involved]), complemento([in, locomotion, to, one, adapted, for, manipulation])]). relacion([sujeto(['Selection', for, overarm, throwing, and, endurance, running, is, thought, to]), verbo([have]), complemento([further, shaped, modern, human, shoulder, girdle, morphology, and, its, position, about, the, thorax])]). relacion([sujeto(['Although', the, 'hand,', 'foot,', and, lower, limb, display, many, derived, 'morphologies,', the, upper, limb]), verbo([retains]), complemento([many, primitive, traits])]). relacion([sujeto(['Although', early, 'Homo', erectus]), verbo([maintains]), complemento([many, primitive, clavicular, and, humeral, 'features,', its, derived, scapular, morphology, suggests, a, loss, of, climbing, adaptations])]). relacion([sujeto([&, 'nbsp;naledi', upper, limb, is, markedly, 'primitive,']), verbo([retaining]), complemento([morphology, conducive, to, climbing, while, lacking, many, of, the, derived, features, related, to, effective, throwing, or, running, purported, to, characterize, other, members, of, early, 'Homo'])]). relacion([sujeto(['The', molecular, framework, will, be, useful, for, the, identification, of, 'Indian', 'Varanus', species, and, trade, products, derived, from, monitors, and, as, 'such,']), verbo([have]), complemento([important, applications, for, wildlife, management, and, conservation])]). relacion([sujeto(['The', neighbor, joining, phylogenetic, tree, and, maximum, parsimony, tree, of, three, mitochondrial, 'genes,', showed, similar, results, and]), verbo([reveal]), complemento(['that,', there, are, two, major, clades, are, present, in, 'Indian', monitor, lizards])]). relacion([sujeto(['These', observations, form, the, basis, of, the, &, 'quot;developmental', origins, of, health, and, 'disease"', 'hypothesis,', which]), verbo([suggests]), complemento([that, the, intrauterine, signals, that, compromise, fetal, growth, also, act, to, &, 'quot;program"', tissue, differentiation, in, a, manner, that, predisposes, to, later, illness])]). relacion([sujeto(['Taken', 'together,', these, findings, form, the, basis, for, integrative, models, of, fetal, 'neurodevelopment,', which, propose, that, antenatal, maternal, adversity, operates, through, the, biological, pathways]), verbo([associated]), complemento([with, fetal, growth, to, program, neurodevelopment])]). relacion([sujeto(['The', authors, review, the, literature, and]), verbo([find]), complemento([little, support, for, such, integrated, models])]). relacion([sujeto(['Rather,', compromised, fetal, development, appears, to, establish, a, &, 'quot;meta-plastic"', state, that]), verbo([increases]), complemento([sensitivity, to, postnatal, influences])]). relacion([sujeto(['There', also, remain, serious, concerns, that, observational, studies]), verbo([associating]), complemento([either, fetal, growth, or, maternal, mental, health, with, neurodevelopmental, outcomes, fail, to, account, for, underlying, genetic, factors])]). relacion([sujeto(['Finally,', while, the, observed, relation, between, fetal, growth, and, adult, health]), verbo([has]), complemento([garnered, considerable, 'attention,', the, clinical, relevance, of, these, associations, remains, to, be, determined])]). relacion([sujeto(['In', the, latency, phase, of, bone, 'lengthening,', like, in, the, inflammatory, phase, of, fracture, 'repair,', interleukines, are]), verbo([released]), complemento([and, act, with, growth, factors, released, from, platelets, in, the, local, 'haematoma,', leading, to, 'attraction,', proliferation, and, differentiation, of, mesenchymal, stem, cells, into, osteoblasts, and, other, differentiated, mesenchymal, cells])]). relacion([sujeto(['Provided', stable, 'fixation,', distraction, will]), verbo([trigger]), complemento([intramembranous, bone, formation])]). relacion([sujeto(['Use', in, children, presents, special, problems, since, growth, factors, and, specific, anabolic, medications, may]), verbo([involve]), complemento([a, risk, of, inducing, cancer])]). relacion([sujeto(['Few', studies]), verbo([have]), complemento([investigated, the, 'thyroid-disrupting', effects, of, polybrominated, diphenyl, ethers, '(', 'PBDEs)', across, multiple, levels, of, biological, organization, in, 'anurans,', despite, their, suitability, for, the, screening, of, thyroid, disruptors])]). relacion([sujeto(['These', results, show, that, 'BDE-47', disrupts, thyroid, hormone, signaling, at, the, molecular, and, 'whole-organism', levels, and]), verbo([suggest]), complemento([that, gene, expression, in, the, brain, is, a, more, sensitive, endpoint, than, metamorphosis])]). relacion([sujeto(['Furthermore,', the, altered, gene, expression, patterns, among, 'BDE-47-exposed', tadpoles]), verbo([provide]), complemento([insight, into, the, mechanisms, of, 'PBDE-induced', thyroid, disruption, and, highlight, the, potential, for, 'PBDEs', to, act, as, neurodevelopmental, toxicants])]). relacion([sujeto(['These', findings, generally]), verbo([suggest]), complemento([that, 'ACT', delivered, via, 'VTC', can, be, as, effective, and, acceptable, as, 'IP', delivery, for, chronic, pain])]). relacion([sujeto(['Future', studies, should, examine, the, optimal, delivery, of, 'ACT', for, patients, with, chronic, pain, who]), verbo([report]), complemento([low, levels, of, activity])]). relacion([sujeto(['This', study]), verbo([suggests]), complemento([that, 'Acceptance', and, 'Commitment', 'Therapy', for, chronic, pain, can, be, implemented, via, 'video-teleconferencing', with, comparable, reductions, in, pain, interference, as, 'in-person', delivery])]). relacion([sujeto(['Formation', of, 'ruthenium(II)', complexes, of, the, type, '[', 'RuH(CO)(PPh3)2(L)]', '(', where, 'L=N-Substituted', 9, -, ethyl, carbazole, thiosemicarbazone, 'ligands)']), verbo([has]), complemento([been, described, from, the, reactions, of, '[', 'RuHCl(CO)(PPh3)3]', and, substituted, carbazole, thiosemicarbazones, in, 1, :, 1, equivalent, respectively])]). relacion([sujeto(['The', solid, state, molecular, structure, of, the, ligands, '(', 'L1-L3)', and, one, of, the, complexes]), verbo([have]), complemento([been, analysed, by, 'single-crystal', 'X-ray', 'studies,', and, found, that, the, 'ruthenium(II)', complexes, possess, a, 'pseudo-octahedral', geometry])]). relacion([sujeto(['The', 'DNA']), verbo([binding]), complemento([interactions, of, the, complexes, with, 'Calf', thymus, 'DNA', have, been, investigated, by, 'absorption,', 'emission,', 'elctrochemical,', circular, dichromism, and, viscosity, measurements, revealed, that, the, complexes, could, interact, with, 'DNA', via, intercalation])]). relacion([sujeto(['Further,', their, protein]), verbo([binding]), complemento([ability, was, monitored, by, the, quenching, of, tryptophan, emission, using, bovine, serum, albumin, '(', 'BSA)', as, a, model, protein])]). relacion([sujeto(['The', potential, of, complexes, to]), verbo([act]), complemento([as, anticancer, agents, is, thoroughly, examined, on, human, cervical, cancer, cell, line, 'HeLa,', 'Osteosarcoma', cell, line, 'MG-63', and, a, normal, mouse, embryonic, fibroblasts, cell, line, 'NIH-3T3', and, screening, shows, the, 'HeLa', cell, line, exhibits, maximum, cytotoxicity])]). relacion([sujeto(['Further,', the, morphological, changes, and, apoptosis]), verbo([have]), complemento([been, evaluated, by, 'AO-EB', staining, techniques, and, flow, cytometry, analysis, against, 'HeLa', cell, line])]). relacion([sujeto(['Cancer', is, characterized, by, cell, heterogeneity, and, the, development, of, 3, 'D', 'in vitro', assays, that, can, distinguish, more, invasive, or, migratory, phenotypes, could]), verbo([enhance]), complemento([diagnosis, or, drug, discovery])]). relacion([sujeto([3, 'D', collagen, scaffolds]), verbo([have]), complemento([been, used, to, develop, analogues, of, complex, tissues, 'in vitro', and, are, suited, to, routine, biochemical, and, immunological, assays])]). relacion([sujeto(['We', sought, to]), verbo([increase]), complemento([3, 'D', model, tractability, and, modulate, the, migration, rate, of, seeded, cells, using, an, 'ice-templating', technique, to, create, either, 'directional/anisotropic', or, 'non-directional/isotropic', porous, architectures, within, 'cross-linked', collagen, scaffolds])]). relacion([sujeto(['Anisotropic', scaffolds, supported, the]), verbo([enhanced]), complemento([migration, of, an, invasive, breast, cancer, cell, line, 'MDA-MB-231', with, an, altered, spatial, distribution, of, proliferative, cells, in, contrast, to, invasive, 'MDA-MB-468', and, 'non-invasive', 'MCF-7 cells', lines])]). relacion([sujeto(['In', 'addition,', 'MDA-MB-468', showed]), verbo([increased]), complemento([migration, upon, 'epithelial-to-mesenchymal', transition, '(', 'EMT)', in, anisotropic, scaffolds])]). relacion([sujeto(['The', provision, of, controlled, architecture, in, this, system, may]), verbo([act]), complemento([both, to, increase, assay, robustness, and, as, a, tuneable, parameter, to, capture, detection, of, a, migrated, population, within, a, set, 'time,', with, consequences, for, primary, tumour, migration, analysis])]). relacion([sujeto(['The', separation, of, invasive, clones, from, a, cancer, biomass, with, 'in vitro', platforms, could]), verbo([enhance]), complemento([drug, development, and, diagnosis, testing, by, contributing, assay, metrics, including, migration, 'rate,', as, well, as, modelling, 'cell-cell', and, 'cell-matrix', interaction, in, a, system, compatible, with, routine, histopathological, testing])]). relacion([sujeto(['Unlike', highly, regenerative, tissues, such, as, the, 'skin,', intestinal, crypts, and, hematopoietic, 'system,', no, dedicated, adult, stem, cells, or, stem, cell, niche]), verbo([have]), complemento([so, far, been, identified, within, the, adult, pancreas])]). relacion([sujeto(['New', β, cells]), verbo([have]), complemento([been, shown, to, form, in, the, adult, 'pancreas,', in, response, to, high, physiological, demand, or, experimental, 'β-cell', 'ablation,', mostly, by, replication, of, existing, β, cells])]). relacion([sujeto(['Under', particular, injury, 'conditions,', fully, differentiated, pancreatic, duct, and, acinar, cells]), verbo([have]), complemento([been, shown, to, dedifferentiate, into, a, 'progenitor-like', 'state,', however, the, 'extent,', to, which, 'ductal,', acinar, or, other, endocrine, cells, contribute, to, restoring, pancreatic, 'β-cell', mass, remains, to, be, resolved])]). relacion([sujeto(['Taken', 'together,', evidence, from, a, number, of, studies]), verbo([suggest]), complemento([that, differentiated, pancreatic, lineages, could, act, as, facultative, progenitor, 'cells,', but, the, extent, to, which, these, contribute, to, 'β-cell', regeneration, 'in vivo', is, still, a, matter, of, contention])]). relacion([sujeto(['Under', those, 'conditions,', the, 'Cys-rich', central, region, of, 'ω-Aga', 'IVA', still]), verbo([retains]), complemento([the, inhibitor, 'Cys', knot, motif, with, three, short, antiparallel, 'β-strands', seen, in, water])]). relacion([sujeto(['However,', '(', 15, ')', 'N', 'HSQC', spectra, of, 'ω-Aga', 'IVA', within, micelles, revealed, that, there, are, radical, changes, to, the, 'toxin\'s', 'C-terminal', tail, and, several, loops, upon]), verbo([binding]), complemento([to, micelles])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, the, membrane, environment, stabilizes, the, structure, of, the, 'toxin,', enabling, it, to, act, in, a, manner, similar, to, other, gating, modifier, 'toxins,', though, its, mode, of, interaction, with, the, membrane, and, the, channel, is, unique])]). relacion([sujeto(['In', prostate, 'cancer,', protein, kinase, 'A', '(', 'PKA)', is, known, to]), verbo([activate]), complemento([the, androgen, receptor, and, published, data, indicate, that, 'PKA', subunits, can, act, as, predictive, markers, for, response, to, radiation, and, chemotherapy])]). relacion([sujeto(['We']), verbo([have]), complemento([previously, shown, that, the, catalytic, 'subunit,', 'Cβ2,', of, 'PKA', is, 'up-regulated', in, prostate, cancer, and, we, would, in, this, study, investigate, the, potential, of, 'Cβ2', to, become, a, prognostic, biomarker, in, prostate, cancer])]). relacion([sujeto(['We']), verbo([suggest]), complemento([that, 'Cβ2', mRNA, expression, may, be, used, as, a, biomarker, together, with, established, prognostic, markers, to, more, precisely, predict, aggressiveness, in, patients, diagnosed, with, prostate, cancer])]). relacion([sujeto(['Polycyclic', aromatic, hydrocarbons, '(', 'PAHs)', are, a, type, of, ubiquitous, pollutant, with, the, potential, ability, to]), verbo([cause]), complemento([endocrine, disruption, that, would, have, an, adverse, health, impact, on, the, general, population])]). relacion([sujeto(['The', highest, level, was]), verbo([found]), complemento([for, pyrene, '(', 'PYR)', and, naphthalene, '(', 'NAP),', which, contributed, 54.6, '%', of, all, the, 'PAHs', present, in, the, samples])]). relacion([sujeto(['The', result, expanded, the, database, of, the, human, burden, of, 'PAHs', and]), verbo([suggested]), complemento([that, 'PAHs', can, act, as, a, type, of, 'Endocrine-Disrupting', 'Chemical', '(', 'EDC)'])]). relacion([sujeto(['These', results, may, help, to, understand, the, complex, pathways]), verbo([involved]), complemento([in, disorders, of, human, reproductive, health, associated, with, prenatal, exposure, to, 'PAHs'])]). relacion([sujeto(['Viewing', good, governance, as, 'accountability,', 'participation,', 'transparency,', intelligence, and, 'integrity,', our, objective, is, to, identify, the, determinants, of, inaction, and, remove, the, barriers, that]), verbo([prevent]), complemento([the, adoption, of, rational, and, widely, 'agreed-upon', proposals])]). relacion([sujeto(['This']), verbo([led]), complemento(['us:', 1, ')', to, allocate, the, proposals, to, their, appropriate, governance, level, '(', 'macro,', 'meso,', micro, and, system, 'environment)', so, as, to, more, directly, engage, the, agents, of, 'change;', and, 2, ')', to, highlight, some, decision, nodes, that, can, act, as, levers, to, catalyse, selective, transformations, and, to, initiate, the, change, processes])]). relacion([sujeto(['Therefore,', the, purpose, of, this, paper, is, to]), verbo([promote]), complemento(['changes,', setting, a, targeted, and, reasoned, agenda, to, visualise, key, issues, and, to, enable, multilevel, and, multidimensional, thinking, and, advocacy, of, 'health-sector', and, society, stakeholders])]). relacion([sujeto(['A', study, of, the, biological, activities, in, guinea, pig, ileum, and, rat, uterus, indicated, that, only, 'Toac(0)-BK', partially]), verbo([maintained]), complemento([its, native, biological, potency, among, the, tested, peptides])]). relacion([sujeto(['This', and, its, 'counterpart,', 'Toac(3)-BK,']), verbo([maintained]), complemento([the, ability, to, act, as, 'ACE', substrates])]). relacion([sujeto(['The', results, also, emphasize, the, existence, of, a, finer, control, for, 'BK-receptor', interaction, than, for, 'BK']), verbo([binding]), complemento([at, the, catalytic, site, of, this, metallodipetidase])]). relacion([sujeto(['The', kinetic, 'kcat/Km', values]), verbo([decreased]), complemento([from, 202.7, to, 38.9, 'μM(-1)min(-1)', for, 'BK', and, 'Toac(3)-BK,', respectively])]). relacion([sujeto(['EPR,', 'CD,', and, fluorescence, experiments]), verbo([reveal]), complemento([a, direct, relationship, between, the, structure, and, activity, of, these, paramagnetic, peptides])]). relacion([sujeto(['Diverse', cell, types, belonging, to, the, innate, or, adaptive, branch, of, the, immune, system]), verbo([act]), complemento([in, a, tightly, coordinated, and, 'tissue-specific', manner])]). relacion([sujeto(['Experimental', mouse, models, of, fungal, infections]), verbo([have]), complemento([proved, essential, for, assessing, the, protective, principles, against, different, fungal, pathogens])]). relacion([sujeto(['Many', 'Gram-negative', bacterial, pathogens, use, type, 'III', secretion, systems, to, export, proteins, that]), verbo([act]), complemento([directly, on, the, host, and, aid, in, the, infectious, process])]). relacion([sujeto(['Intracellular', bacteria, can, also, depend, on, the, 'T3SS', translocation, of, effector, proteins, from, vacuolar, compartments, into, the, vacuolar, membrane, or, host, cell, cytosol, where, they, can]), verbo([modulate]), complemento([intracellular, trafficking, 'and/or', signaling, pathways, necessary, for, their, growth, and, survival])]). relacion([sujeto(['In', this, chapter, we]), verbo([provide]), complemento([methods, for, the, analysis, of, translocated, effector, proteins, using, biochemical, and, mechanical, fractionation, procedures])]). relacion([sujeto(['Twenty-four', percent, of, 'self-employed', cancer, survivors]), verbo([reported]), complemento([that, they, had, not, returned, to, work, at, the, time, of, the, 'survey,', and, 18, &, 'nbsp;%', of, those, who, were, salaried, had, not])]). relacion([sujeto(['Compared', with, the, salaried, 'workers,', the, 'self-employed', people]), verbo([reported]), complemento([significantly, more, often, reduced, work, hours, '(', 'P < 0'])]). relacion([sujeto(['The', negative, effect, of, 'self-employment', on, total, work, ability, seems, to, be]), verbo([mediated]), complemento([by, reduced, work, hours, and, a, negative, 'cancer-related', financial, change])]). relacion([sujeto(['This', may, be, because, the, two, groups]), verbo([have]), complemento([different, work, tasks, and, because, 'self-employed', people, have, lower, social, support, at, work, and, less, legal, support, from, the, 'Working', 'Environment', 'Act', and, public, health, insurance])]). relacion([sujeto(['Aim', of, this, work, was, to, assess, the, role, of, polymorphisms, belonging, to, genes]), verbo([involved]), complemento([in, the, regulation, of, ionic, homeostasis, in, 'Caucasian', patients, with, 'Ménière', 'Disease', '(', 'MD)'])]). relacion([sujeto(['We']), verbo([recruited]), complemento([155, patients, with, definite, 'Ménière', 'Disease', and, 186, controls, '(', 'Control', 'Group', 1, ')', without, a, lifetime, history, of, 'vertigo,', overlapping, with, patients, for, age, and, rate, of, hypertension])]). relacion([sujeto(['The', clinical, history, for, migraine, and, hypertension, was, 'collected;', genomic, 'DNA', was, characterized, for, a, panel, of, 33, 'SNPs', encoding, proteins]), verbo([involved]), complemento([in, ionic, transport])]). relacion([sujeto(['We']), verbo([found]), complemento([a, higher, rate, of, migraineurs, in, 'MD', subjects, compared, to, 'Group', 1, '(', 46.8, vs, 15.5, '%', ',', 'p = 0'])]). relacion([sujeto(['SLC8A1', gene, encodes, for, 'Na(+)-Ca(++)', 'exchanger,', while, 'SIK1', gene, encodes, for, 'Salt', 'Inducible', 'Kinase', 1, ',', an, enzyme]), verbo([associated]), complemento([with, 'Na(+)-K(+)', 'ATPase', function])]). relacion([sujeto(['The', validation, with, 'Control', 'Group', 2, displayed, that, only, rs3746951, and, rs487119, are, strongly]), verbo([associated]), complemento([to, 'MD', '(', 'p = 0'])]). relacion([sujeto(['These', data, support, the, hypothesis, that, a, genetically]), verbo([induced]), complemento([dysfunction, of, ionic, transport, may, act, as, a, predisposing, factors, to, develop, 'MD'])]). relacion([sujeto(['In', this, narrative, 'review,', the, neurobiological, mechanisms, underlying, substance, abuse, and, addiction, are, discussed, with, a, particular, emphasis, on, the, mechanisms, that]), verbo([promote]), complemento([ongoing, use, and, relapse])]). relacion([sujeto(['Abused', substances]), verbo([act]), complemento([on, the, 'brain\'s', reward, 'system,', a, neural, circuit, that, produces, pleasurable, feelings, in, response, to, stimuli, that, promote, 'survival,', thereby, modifying, future, behavior, to, seek, out, similar, stimuli])]). relacion([sujeto(['Repetitive', exposure, to, substances]), verbo([leads]), complemento([to, 'persistent,', altered, genetic, expression, and, accumulation, of, 'ΔFos-B', and, 'corticotropin-releasing', factor])]). relacion([sujeto(['High', levels, of, these, substances]), verbo([suppress]), complemento([the, reward, circuit, and, activate, the, endogenous, stress, 'response,', resulting, in, a, generalized, state, of, discord])]). relacion([sujeto(['These', changes, are, enduring, and, can]), verbo([trigger]), complemento([substance, use, relapse, even, after, long, periods, of, abstinence])]). relacion([sujeto(['Readmissions', after, total, joint, arthroplasty]), verbo([have]), complemento([become, a, key, quality, measure, in, elective, surgery, in, the, 'United', 'States'])]). relacion([sujeto(['The', reasons, or, conditions]), verbo([associated]), complemento([with, readmission, after, elective, 'THA', have, been, well, established, but, the, extent, to, which, readmissions, can, be, prevented, after, 'THA', remains, unclear])]). relacion([sujeto(['(', 1, ')', 'Are', unplanned, readmissions, after, 'THA']), verbo([associated]), complemento([with, orthopaedic, or, medical, 'causes?', '(', 2, ')', 'Are', these, readmissions, 'preventable?', '(', 3, ')', 'When', during, the, course, of, aftercare, are, orthopaedic, versus, medical, readmissions, more, likely, to, 'occur?', 'We', retrospectively, evaluated, all, 1096, elective, 'THAs', for, osteoarthritis, performed, between, 'January', 1, ',', 2011, and, 'June', 30, ',', 2014, at, a, major, academic, medical, center])]). relacion([sujeto(['A', panel, of, physicians, not]), verbo([involved]), complemento([in, the, care, of, these, patients, used, available, criteria, and, existing, consensus, guidelines, to, evaluate, the, medical, 'records,', 'radiographs,', and, operative, reports, to, identify, whether, the, underlying, reason, for, readmission, was, orthopaedic, versus, medical])]). relacion([sujeto(['They', subsequently, were, classified, as, either, nonpreventable, or, potentially, preventable, 'readmissions,', based, on, any, care, that, may]), verbo([have]), complemento([occurred, during, the, index, hospitalization])]). relacion([sujeto(['Future', studies, should, enroll, larger, numbers, of, patients, and]), verbo([have]), complemento([independent, review, panels, in, efforts, to, refine, criteria, for, what, constitutes, preventable, readmissions])]). relacion([sujeto(['Total', 'ED', visits]), verbo([increased]), complemento([5.6, '%', in, 'Illinois', after, 'ACA', 'implementation,', with, virtually, no, change, in, hospital, admissions])]). relacion([sujeto(['The', proportion, of, uninsured, 'ED', hospitalizations, classified, as, 'ACSH']), verbo([increased]), complemento([from, 15.4, to, 15.5, '%', ',', a, 'non-significant', difference])]). relacion([sujeto(['The', objective, of, this, study, was, to, describe, the, efficacy, and, safety, of, a, pharmacy, managed, heparin, protocol, utilizing]), verbo([activated]), complemento([partial, thromboplastin, time, '(', 'aPTT)', in, comparison, to, our, standard, 'physician-managed', activated, clotting, time, '(', 'ACT)-based', anticoagulation, in, 'ECMO', patients])]). relacion([sujeto(['A', pharmacy, managed, heparin, protocol, utilizing, aPTT, monitoring, appears, to, be, a, safe, and, effective, method, of]), verbo([providing]), complemento([anticoagulation, in, adult, 'ECMO', patients])]). relacion([sujeto(['The', root, vascular, tissues]), verbo([provide]), complemento([an, excellent, system, for, studying, organ, 'patterning,', as, the, specification, of, these, tissues, signals, a, transition, from, radial, symmetry, to, bisymmetric, patterns])]). relacion([sujeto(['With', the, discovery, of, multiple, components, and, feedback, loops, controlling, 'patterning,', it]), verbo([has]), complemento([become, increasingly, difficult, to, understand, how, these, interactions, act, in, unison, to, determine, pattern, formation, in, multicellular, tissues])]). relacion([sujeto(['Three', independent, mathematical, models, of, root, vascular, patterning]), verbo([have]), complemento([been, formulated, in, the, last, few, 'years,', providing, an, excellent, example, of, how, theoretical, approaches, can, complement, experimental, studies, to, provide, new, insights, into, complex, systems])]). relacion([sujeto(['In', many, aspects, these, models, support, each, 'other;', 'however,', each, study, also]), verbo([provides]), complemento([its, own, novel, findings, and, unique, viewpoints])]). relacion([sujeto(['We', show, that, the, xylem, axis, can]), verbo([act]), complemento([as, a, sole, source, of, cytokinin, and, specify, the, correct, 'pattern,', but, also, that, broader, patterns, of, cytokinin, production, are, also, able, to, pattern, the, root])]). relacion([sujeto(['By', comparing, the, three, modeling, 'approaches,', we]), verbo([gain]), complemento([further, insight, into, vascular, patterning, and, identify, several, key, areas, for, experimental, investigation])]). relacion([sujeto(['Pain']), verbo([has]), complemento([been, suggested, to, act, as, a, stressor, during, 'aging,', potentially, accelerating, declines, in, health, and, functioning])]). relacion([sujeto(['The', study, population, consisted, of, 5, ',', 316, men, and, women, living, in, private, households, in, 'England,', mean, age, 64.5, 'years,']), verbo([participating]), complemento([in, the, 'English', 'Longitudinal', 'Study', of, 'Ageing', '(', 'ELSA)'])]). relacion([sujeto(['At', 'Wave', 2, ',', participants, were, asked, whether, they, were, &, 'quot;often', troubled, with, 'pain"', and, for, those, who]), verbo([reported]), complemento(['yes,', further, information, regarding, the, intensity, of, their, pain, '(', 'mild,', 'moderate,', or, 'severe)', was, collected])]). relacion([sujeto(['At', 'Wave', 2, ',', 455, '(', 19.7, '%', ')', men, and, 856, '(', 28.7, '%', ')', women]), verbo([reported]), complemento([they, often, experienced, moderate, or, severe, pain])]). relacion([sujeto(['After', adjustment, for, 'age,', 'gender,', body, mass, 'index,', lifestyle, 'factors,', and, depressive, 'symptoms,', compared, to, participants]), verbo([reporting]), complemento([no, pain, at, 'Wave', 2, those, reporting, moderate, '(', odds, ratio, '[', 'OR]', =, 3.08, ',', 95, '%', confidence, interval, '[', 'CI]', =, 2.28, ',', 4.16, ')', or, severe, pain, '(', 'OR', =, 3.78, ',', 95, '%', 'CI', =, 2.51, ',', 5.71, ')', were, significantly, more, likely, to, be, frail, at, 'Wave', 6])]). relacion([sujeto(['Pain', is]), verbo([associated]), complemento([with, an, increased, risk, and, intensity, of, frailty, in, older, men, and, women])]). relacion([sujeto(['The', prevalence, of, a, sedentary, '(', 'SED)', life, style, combined, with, calorically, rich, diets]), verbo([has]), complemento([spurred, the, rise, in, childhood, obesity, 'which,', in, 'turn,', translates, to, adverse, health, effects, in, adulthood])]). relacion([sujeto(['Obesity', and, lack, of, active, '(', 'ACT)', lifestyle, may]), verbo([increase]), complemento([susceptibility, to, air, pollutants])]). relacion([sujeto(['BALF', cell, neutrophils, and, total, cells, were, similarly]), verbo([increased]), complemento([in, 'ACT', and, 'SED', groups, exposed, to, 1.0, ppm, 'O3'])]). relacion([sujeto(['O3-induced']), verbo([increase]), complemento([in, eosinophils, was, exacerbated, in, 'SED', rats])]). relacion([sujeto(['The', reduction, in, 'O3-induced', rise, in, 'BALF', eosinophils, in, 'ACT', rats]), verbo([suggests]), complemento([a, possible, link, between, a, 'SED', lifestyle, and, incidence, of, 'asthma-related', symptoms, from, 'O3'])]). relacion([sujeto(['Here,', we]), verbo([found]), complemento([that, activation, of, 'G', 'protein-coupled', estrogen, receptor, '(', 'GPER)', by, its, specific, agonist, 'G-1', can, significantly, inhibit, interleukin, 6, '(', 'IL-6)', and, vascular, endothelial, growth, factor, 'A', '(', 'VEGF-A)'])]). relacion([sujeto(['TNBC', tissue, microarrays, from, 100, 'TNBC', patients, revealed, 'GPER', is, negatively]), verbo([associated]), complemento([with, 'IL-6', levels, and, higher, grade, and, stage])]). relacion([sujeto(['Activation', of, 'GPER', or, 'anti-IL-6', antibody, can]), verbo([inhibit]), complemento([both, 'in vitro', tube, formation, of, human, umbilical, vein, endothelial, cells, '(', 'HUVECs)', and, migration, of, 'TNBC', cells])]). relacion([sujeto(['While', recombinant, 'IL-6', supplementary, can, significantly, reverse, the, inhibitory, effects, of, 'G-1,']), verbo([suggesting]), complemento([the, essential, role, of, 'IL-6', in, 'G-1', induced, suppression, of, angiogenesis, and, invasiveness, of, 'TNBC', cells])]). relacion([sujeto(['G-1', treatment]), verbo([decreased]), complemento([the, 'phosphorylation,', nuclear, 'localization,', transcriptional, activities, of, 'NF-κB', and, suppressed, its, binding, with, 'IL-6', promoter])]). relacion([sujeto(['The', suppression, of, 'IL-6', by, 'G-1', can, further]), verbo([inhibit]), complemento(['HIF-1α', and, 'STAT3', signals, in, 'TNBC', cells, by, inhibition, their, 'expression,', phosphorylation, 'and/or', nuclear, localization])]). relacion([sujeto(['Moreover,', 'G-1', also]), verbo([inhibited]), complemento([the, 'in vivo', 'NF-κB/IL-6', signals, and, angiogenesis, and, metastasis, of, 'MDA-MB-231', xenograft, tumors])]). relacion([sujeto(['In', 'conclusion,', our, study, demonstrated, that, activation, of, 'GPER', can]), verbo([suppress]), complemento([migration, and, angiogenesis, of, 'TNBC', via, inhibition, of, 'NF-κB/IL-6', 'signals,', therefore, it, maybe, act, as, an, important, target, for, 'TNBC', treatment])]). relacion([sujeto(['This', is, currently, explained, by, coherent, coupling, of, the, excited, state, electronic, wavepacket, with, local, vibrational]), verbo([nuclear]), complemento(['modes,', facilitating, efficient, 'cross-over', at, a, conical, intersection, onto, the, photoproduct, energy, surface])]). relacion([sujeto(['The', 9, -, cis, counterpart, of, 'rhodopsin,', dubbed, 'isorhodopsin,']), verbo([has]), complemento([a, much, lower, quantum, yield, '(', 0.26, '±0'])]). relacion([sujeto([3, ')', ',', 'which,', 'however,', can, be, markedly]), verbo([enhanced]), complemento([by, modification, of, the, retinal, chromophore, '(', 7, ',', 8, -, dihydro, and, 9, -, cyclopropyl, 'derivatives)'])]). relacion([sujeto(['The', coherent, coupling, in, the, excited, state, is]), verbo([promoted]), complemento([by, torsional, skeletal, and, coupled, 'HOOP', vibrational, 'modes,', in, combination, with, a, twisted, conformation, around, the, isomerization, region])]). relacion([sujeto(['Since', such, torsion, will, strongly]), verbo([enhance]), complemento([the, infrared, intensity, of, coupled, 'HOOP', 'modes,', we, investigated, 'FTIR', difference, spectra, of, 'rhodopsin,', isorhodopsin, and, several, analog, pigments, in, the, spectral, range, of, isolated, and, coupled, 'HCCH', wags])]). relacion([sujeto(['As', such, the, 'HOOP', signature, can]), verbo([act]), complemento([as, an, indicator, for, the, photoisomerization, 'efficiency,', and, can, explain, the, higher, quantum, yield, of, the, 7, ',', 8, -, dihydro, and, 9, -, 'cyclopropyl-isorhodopsin', analogs])]). relacion([sujeto(['Laser', engraving, and, holes, in, 'PMMA', along, with, spacing, from, surface]), verbo([provide]), complemento([fluidic, channel, and, incubation, chamber])]). relacion([sujeto(['Covalent']), verbo([binding]), complemento([of, capturing, biomolecule, '(', 'anti-TNF-α', 'antibody)', on, 'off-surface', matrix, was, achieved, via, azide, group, activity, of, 4, -, 'fluoro-3-nitro-azidobenzene', '(', 'FNAB),', which, act, as, 'cross-linker', and, further, covalently, binds, to, 'anti-TNF-α', antibody, via, thermal, reaction])]). relacion([sujeto(['Separate', surface, modification, followed, by, integration, of, sensor, helped, to]), verbo([prevent]), complemento([the, sensor, chip, surface, from, fouling, during, functionalization])]). relacion([sujeto(['Nonspecific']), verbo([binding]), complemento([was, prevented, using, starting, block, 'T20', '(', 'PBS)'])]). relacion([sujeto(['Results', for, estimating, protein, biomarker, '(', 'TNF-α)', in, undiluted, serum, using, 'Anti-TNF-α/FNAB/PMMA/Au']), verbo([reveal]), complemento([that, system, can, detect, 'TNF-α', in, 100, 'pg/ml', to, 100, 'ng/ml', range, with, high, sensitivity, of, 119, 'nA/(ng/ml),', with, negligible, interference, from, serum, proteins, and, other, cytokines])]). relacion([sujeto(['Thus,', use, of, off, surface, matrix, may]), verbo([provide]), complemento([the, opportunity, to, electrochemically, sense, biomarkers, sensitively, to, 'ng/ml', range, with, negligible, nonspecific, binding, and, false, signal, in, undiluted, serum])]). relacion([sujeto(['They']), verbo([act]), complemento([as, amplification, probes, which, aggregate, numerous, gold, nanoparticles, '(', 'AuNPs)', on, test, line, by, forming, a, 'three-dimensional', 'DNA-AuNPs', network, structure, in, the, presence, of, target])]). relacion([sujeto(['The', use, of, these, particles, in, rapid, ultrasensitive, point, of, care, '(', 'POC)', lateral, flow, assays]), verbo([lead]), complemento([to, a, linear, range, from, 0.1, pM, to, 250, nM, with, a, limit, of, detection, of, 0.01, pM, without, polymerase, chain, reaction, '(', 'PCR)'])]). relacion([sujeto(['The', proposed, method, could]), verbo([increase]), complemento([the, sensitivity, by, 4, orders, of, magnitudes, than, traditional, sandwich, assays, labeled, with, 'AuNPs'])]). relacion([sujeto(['This', study, was, designed, to, assess, the, neuroprotective, effect, of, naringin, on, ammonium, chloride, '(', 'NH4Cl)']), verbo([induced]), complemento([hyperammonemic, rats])]). relacion([sujeto(['Experimental', hyperammonemia, was]), verbo([induced]), complemento([by, intraperitonial, injection, '(', i])]). relacion([sujeto(['Hence,', this, study]), verbo([suggested]), complemento([that, nargingin, exhibited, their, protective, effect, against, 'NH4Cl', induced, toxicity, via, enhancing, the, activities, of, antioxidant, enzymes, and, inhibiting, the, lipid, peroxidation, process])]). relacion([sujeto(['Take', 'together,', this, study]), verbo([provides]), complemento([data, that, naingin, effectively, reduced, neurotoxicity, by, attenuating, 'hyperammonemia,', suggesting, that, naringin, act, as, a, potential, therapeutic, agent, to, treat, hyperammonemic, rats])]). relacion([sujeto(['One', group, of, myosin, 'motors,', the, 'MyTH4-FERM', 'myosins,', play, an, integral, part, in, building, and]), verbo([maintaining]), complemento(['finger-like', 'protrusions,', which, allow, cells, to, interact, with, their, external, environment])]). relacion([sujeto(['Suggested', to]), verbo([act]), complemento([primarily, as, 'transporters,', these, motor, proteins, enrich, adhesion, 'molecules,', 'actin-regulatory', proteins, and, other, factors, at, the, tips, of, 'filopodia,', 'microvilli,', and, stereocilia])]). relacion([sujeto(['The', grey, mullet, usually, occur, in, large, numbers, and, biomass, in, the, estuaries, of, all, three, 'South', 'African', biogeographic, 'regions,', thus, making, it, an, ideal, family, to, use, in, terms, of, possibly]), verbo([acting]), complemento([as, an, environmental, indicator, of, global, warming])]). relacion([sujeto(['In', this, analysis, the, relative, estuarine, abundance, of, the, dominant, three, groups, of, 'mugilids,', namely, 'tropical,', 'warm-water', and, 'cool-water', 'endemics,', were, related, to]), verbo([sea]), complemento([surface, coastal, temperatures])]). relacion([sujeto(['The', study]), verbo([suggests]), complemento([a, strong, link, between, temperature, and, the, distribution, and, abundance, of, the, three, mullet, groups, within, estuaries, and, indicates, the, potential, of, this, family, to, act, as, an, indicator, for, future, climate, change, within, these, systems, and, adjacent, coastal, waters])]). relacion([sujeto(['The', purpose, of, this, study, is, to, explore, emergency, 'nurses\'', perceptions, of, factors]), verbo([involved]), complemento([in, safe, staffing, levels, and, to, identify, factors, that, negatively, and, positively, influence, staffing, levels, and, might, lend, themselves, to, more, effective, interventions, and, evaluations])]). relacion([sujeto(['Participants']), verbo([reported]), complemento([that, staffing, levels, are, determined, by, the, number, of, beds, in, the, department, '(', as, in, inpatient, 'units)', but, not, by, patient, acuity, or, the, number, of, patients, waiting, for, treatment])]). relacion([sujeto(['Both', absolute, numbers, of, 'staff,', as, well, as, skill, and, experience, 'mix,', should, be, considered, to]), verbo([provide]), complemento([staffing, levels, that, promote, optimal, patient, and, nurse, outcomes])]). relacion([sujeto(['Pharmacists', were, excluded, from, detailed, analysis, due, to, the, low, numbers, that]), verbo([responded]), complemento(['(', 'n=3)'])]). relacion([sujeto(['The', 'SQP', participants, indicated, that, they, felt, a, large, number, of, organisations, were, responsible, for]), verbo([ensuring]), complemento([that, anthelmintics, are, used, 'responsibly,', whilst, veterinarian, participants, were, more, likely, to, place, responsibility, on, the, prescribers, alone])]). relacion([sujeto(['Taken', 'together,', these, findings]), verbo([provide]), complemento([an, insight, into, how, prescribers, of, anthelmintics, in, the, 'UK', interact, with, their, 'clients/customers', before, and, at, the, point, of, sale, and, act, as, a, unique, source, of, information, on, how, best, practice, advice, pertaining, to, sustainable, helminth, control, is, disseminated, by, the, various, prescribing, channels])]). relacion([sujeto(['Mean', vitamin, 'D', intake, in, the, sample]), verbo([increased]), complemento([significantly, from, 'pre-test', '(', 'M', =, 407, ',', 'SD', =, 460, &, 'nbsp;IU)', to, 'post-test', '(', 'M', =, 619, ',', 'SD', =, 655, &, 'nbsp;IU),', 't(88)', =, 5.37, ',', p, &, 'lt;', 0.001])]). relacion([sujeto(['Mean', intake]), verbo([increased]), complemento([significantly, more, in, the, intervention, than, control, group, after, controlling, for, gender, and, 'education,', 'F(1,', 85, ')', =, 4.09, ',', p, =, 0.046])]). relacion([sujeto(['Mean', blood, vitamin, 'D3']), verbo([increased]), complemento([significantly, from, 'pre-test', '(', 'M', =, 28, ',', 'SD', =, 16, &, 'nbsp;nmol/L)', to, 'post-test', '(', 'M', =, 43, ',', 'SD', =, 29, &, 'nbsp;nmol/L),', 't(53)', =, 11.36, ',', p, &, 'lt;', 0.001, ',', but, did, not, differ, significantly, between, groups])]). relacion([sujeto(['The']), verbo([increase]), complemento([in, vitamin, 'D', knowledge, from, time, 1, -, 3, was, significantly, higher, in, the, intervention, than, control, group, '(', 't(88)', =, 2.26, ',', p, =, 0.03, ')'])]). relacion([sujeto(['Although', recommendations]), verbo([suggest]), complemento([blood, 25, '(', 'OH)D3', concentrations, of, '≥50-75 nmol/L,', vitamin, 'D', status, was, below, national, recommendations])]). relacion([sujeto(['While']), verbo([participating]), complemento([in, an, intervention, did, not, improve, vitamin, 'D', 'status,', it, led, to, increased, vitamin, 'D', 'intake,', knowledge, and, perceived, importance, of, supplementation])]). relacion([sujeto(['Preschools', and, childcare, settings, offer, opportunities, to]), verbo([promote]), complemento([adequate, levels, of, physical, activity])]). relacion([sujeto(['In', the, final, adjusted, 'models,', number, of, outdoor, spaces, with, natural, ground, coverings, was]), verbo([associated]), complemento([with, 'boys\'', physical, activity, '(', coeff, =, 0.477, ',', 95, &, 'nbsp;%', 'CI', 0.089, ',', 0.867, ')', and, the, amount, of, time, girls, spent, indoors, before, going, outdoors, was, inversely, associated, with, their, physical, activity, '(', coeff, =, -, 0.035, ',', 95, &, 'nbsp;%', 'CI', -, 0.065, ',', -, 0.004, ')'])]). relacion([sujeto(['Disinvestment', and, reinvestment, through, the, 'HTR', was, used, to]), verbo([increase]), complemento([the, efficiency, and, quality, of, care, to, help, patients, receive, optimal, treatment])]). relacion([sujeto(['While', the, household, context, is, important, for, lifestyle, behavior, 'interventions,', few, studies]), verbo([have]), complemento([examined, 'parent-child', associations, for, diet, and, physical, activity, '(', 'PA)', changes, over, time, in, a, rapidly, urbanizing, country])]). relacion([sujeto(['We', observed]), verbo([increases]), complemento([in, energy, from, 'animal-source', 'foods,', eating, 'away-from-home,', and, 'snacking,', as, well, as, screen, time, and, 'leisure-time', sports, in, parents, and, children, over, 'time,', with, different, rates, of, change, between, children, and, their, parents, for, some, behaviors])]). relacion([sujeto(['We']), verbo([found]), complemento([positive, 'parent-child', associations, for, 'diet,', screen, 'time,', and, 'PA'])]). relacion([sujeto(['When', parental, intakes]), verbo([increased]), complemento([by, 10, &, 'nbsp;%', energy, from, each, dietary, 'behavior,', 'children\'s', increase, in, intakes, ranged, from, 0.44, to, 1.59, &, 'nbsp;%', total, energy, for, 'animal-source', 'foods,', 0.17, &, 'nbsp;%', to, 0.45, &, 'nbsp;%', for, 'away-from-home', 'eating,', and, 2.13, &, 'nbsp;%', to, 7.21, &, 'nbsp;%', for, snacking])]). relacion([sujeto(['Children', were, also, more, likely, to]), verbo([participate]), complemento([in, 'leisure-time', sports, if, their, parents, participated, in, 'leisure-time', sports])]). relacion([sujeto(['Our', findings, support, 'household-based', health, behavior, interventions]), verbo([targeting]), complemento([both, children, and, their, parents])]). relacion([sujeto(['Cachexia', is, defined, as, a, complex, metabolic, syndrome]), verbo([associated]), complemento([with, underlying, illness, and, a, loss, of, muscle, with, or, without, loss, of, fat, mass])]). relacion([sujeto(['This', disease, is]), verbo([associated]), complemento([with, high, incidence, with, chronic, diseases, such, as, heart, 'failure,', 'cancer,', chronic, obstructive, pulmonary, 'disease,', 'AIDS,', among, others])]). relacion([sujeto(['Since', there, is, currently, no, effective, treatment, 'available,', cachectic, patients]), verbo([have]), complemento([a, poor, prognosis])]). relacion([sujeto([',', which]), verbo([act]), complemento([on, skeletal, muscle])]). relacion([sujeto(['There,', they]), verbo([induce]), complemento([a, set, of, genes, called, atrogenes, which, among, others, induce, the, 'ubiquitin-proteasome', 'system,', leading, to, protein, degradation])]). relacion([sujeto(['Moreover,', elevated, 'ROS', levels, due, to, modulation, of, 'NADPH', oxidases, and, mitochondrial, function, contribute, to, disease, 'progression,', which, is, characterized, by]), verbo([loss]), complemento([of, muscle, 'mass,', exercise, 'resistance,', and, frailty])]). relacion([sujeto(['With', the, identification, of, key, components, of, the, aberrant, 'inter-organ', communication]), verbo([leading]), complemento([to, 'cachexia,', studies, in, mice, and, men, to, inhibit, cachexia, demonstrated, that, inhibition, of, 'ROS', 'formation,', induction, of, 'anti-oxidative', 'SOD´s,', and, upregulation, of, muscular, 'NO', formation, either, by, pharmacological, tools, or, by, exercise, are, promising, approaches, to, reduce, the, extent, of, skeletal, muscle, wasting])]). relacion([sujeto(['Cachexia,', which, is, frequently]), verbo([associated]), complemento([with, chronic, disease, 'states,', may, represent, an, important, target, of, 'anti-oxidative', 'therapies,', underscoring, the, need, for, specific, tools, to, modulate, cellular, 'ROS', formation])]). relacion([sujeto(['RUNX3']), verbo([suppressed]), complemento(['RCC', metastasis, and, invasion, and, increased, levels, of, 'E-cadherin,', an, important, marker, of, 'epithelial-mesenchymal', 'transition,', in, vitro, and, in, vivo])]). relacion([sujeto(['RUNX3', also]), verbo([inhibited]), complemento(['microRNA-6780a-5p,', which, directly, targeted, the, 'E-cadherin', 3, '\'', untranslated, region, and, decreased, its, expression])]). relacion([sujeto(['Thus,', 'RUNX3']), verbo([targeted]), complemento([the, 'miR-6780a-5p/E-cadherin/EMT', signaling, axis, to, suppress, renal, carcinoma, cell, migration, and, invasion])]). relacion([sujeto(['This', pathway, illustrates, a, new, 'RUNX3', function, and]), verbo([provides]), complemento([potential, targets, for, the, treatment, of, 'RUNX3', mutant, and, 'loss-of-function', 'RCC', tumors])]). relacion([sujeto(['RUNX3', may, also]), verbo([act]), complemento([as, an, effective, prognostic, indicator, in, 'RCC'])]). relacion([sujeto(['We', recently]), verbo([reported]), complemento([that, apocynin, had, benefits, for, preventing, cardiovascular, diseases])]). relacion([sujeto(['The', results, showed, that, serum, level, of, 'Ang', 'II', was, significantly]), verbo([increased]), complemento([in, patients, with, high, 'ABI', '(', 'P<0'])]). relacion([sujeto(['Apocynin']), verbo([enhanced]), complemento([expression, of, 'a-SMA', by, 5.3, '%', ',', and, reduced, expression, of, 'BMP2,', 'Runx2,', 'OPN', by, 3.37, '%', ',', 0.61, '%', and, 3.07, '%', ',', respectively])]). relacion([sujeto(['Apocynin', may]), verbo([act]), complemento([as, a, novel, molecular, candidate, to, protect, against, 'VSMCs', osteogenic, switching, through, suppressing, 'ERK1/2', pathway])]). relacion([sujeto(['The', 'as-prepared', 'NHPC']), verbo([has]), complemento([a, large, specific, surface, area, of, 1150, 'm(2)·g(-1),', and, a, high, nitrogen, content, of, 14.5, wt])]). relacion([sujeto(['Moreover,', these, 'nitrogen-doped', hierarchical, porous, carbons, exhibit, a, great, potential, to]), verbo([act]), complemento([as, electrode, materials, for, 'supercapacitors,', which, could, deliver, high, specific, capacitance, of, 214.0, 'F·g(-1)', with, an, excellent, rate, capability, of, 74.7, '%', from, 0.1, to, 10, 'A·g(-1)'])]). relacion([sujeto(['This', kind, of, new, 'nitrogen-doped', hierarchical, porous, carbons, with, controllable, hierarchical, porosity, and, chemical, composition, may]), verbo([have]), complemento([a, good, potential, in, the, future, applications])]). relacion([sujeto(['To', determine, what, alternative, pathways, may]), verbo([act]), complemento([as, mechanisms, of, bypass, resistance, to, type, 1, 'insulin-like', growth, factor, receptor, '(', 'IGF-1R)', blockade, in, rhabdomyosarcoma, '(', 'RMS),', we, compared, expression, of, receptor, tyrosine, kinase, activity, in, a, number, of, 'IGF-1R', 'antibody-resistant', and, -, sensitive, 'RMS', cell, lines])]). relacion([sujeto(['We']), verbo([found]), complemento([that, 'platelet-derived', growth, factor, receptor, β, '(', 'PDGFR-β)', activity, was, upregulated, in, three, 'xenograft-derived', 'IGF-1R', 'antibody-resistant', cell, lines, that, arose, from, a, highly, sensitive, 'fusion-positive', 'RMS', cell, line, '(', 'Rh41)'])]). relacion([sujeto(['In', the, seven, cell, lines, 'described,', we, observed]), verbo([enhanced]), complemento([growth, inhibition, when, cells, were, treated, with, dual, 'IGF-1R', and, 'PDGFR-β', inhibition, in, vitro])]). relacion([sujeto(['In', vivo, studies]), verbo([have]), complemento([confirmed, the, enhanced, effect, of, targeting, 'IGF-1R', and, 'PDGFR-β', in, several, mouse, xenograft, models, of, 'fusion-negative', 'RMS'])]). relacion([sujeto(['These', findings]), verbo([suggest]), complemento([that, 'PDGFR-β', acts, as, a, bypass, resistance, pathway, to, 'IGF-1R', inhibition, in, a, subset, of, 'RMS'])]). relacion([sujeto(['CDs']), verbo([act]), complemento([as, coating, and, stabilizing, 'agent,', protecting, 'AgNPs', from, aggregation, and, oxidation])]). relacion([sujeto(['This', research, aims, to, explore, the, neural, correlates]), verbo([involved]), complemento([in, altruistic, 'punishment,', parochial, altruism, and, 'anti-social', 'punishment,', using, the, 'Third-Party', 'Punishment', '(', 'TPP)', game])]). relacion([sujeto(['The', results, showed, that, participants]), verbo([act]), complemento([altruistically, to, protect, 'in-group', members])]). relacion([sujeto(['This', study, indicates, that, norm, violation, in, 'in-group', '(', but, not, in, 'out-group)', settings, results, in]), verbo([increased]), complemento([activity, in, the, medial, prefrontal, cortex, and, 'temporo-parietal', 'junction,', brain, regions, involved, in, the, mentalizing, 'network,', as, the, 'third-party', attempts, to, understand, or, justify, 'in-group', 'members\'', behavior])]). relacion([sujeto(['Finally,', exploratory, analysis, during, 'anti-social', punishment, behavior, showed, brain, activation, recruitment, of, the, ventromedial, prefrontal, 'cortex,', an, area]), verbo([associated]), complemento([with, altered, regulation, of, emotions])]). relacion([sujeto(['Furthermore,', the, deregulation, of, 'AR', activity, is]), verbo([involved]), complemento([in, the, initiation, of, prostate, cancer, and, contributes, to, castration, resistant, prostate, cancer, '(', 'CRPC)'])]). relacion([sujeto(['PC-1', is, an, 'androgen-responsive', factor, and]), verbo([expresses]), complemento([specificity, in, prostate, 'cancer,', with, higher, expression, noted, at, 'G2/M'])]). relacion([sujeto(['In', this, 'study,', 'PC-1', was, shown, to]), verbo([interact]), complemento([with, 'AR', and, 'E3', ligase, 'CHIP', '(', 'Carboxy-terminus', of, 'Hsc70', 'Interacting', 'Protein)', and, to, enhance, 'AR/CHIP', 'interactions,', thereby, decreasing, 'AR', stability])]). relacion([sujeto(['Moreover,', 'PC-1', was]), verbo([found]), complemento([to, act, in, conjunction, with, 'CHIP', in, the, decreasing, of, 'AR', via, 'ubiquitination,', with, the, subsequent, degradation, predominantly, occurring, during, 'M', phase])]). relacion([sujeto(['PC-1', was, also]), verbo([found]), complemento([to, repress, 'AR', transcriptional, activity, in, 'androgen-dependent', and, 'androgen-independent', prostate, cancer, cells, and, attenuate, the, growth, inhibition, of, 'AR'])]). relacion([sujeto(['In', 'conclusion,', these, findings, should]), verbo([provide]), complemento([new, clues, regarding, the, modulation, of, 'AR', turnover, and, activity, via, 'PC-1', and, reveals, an, essential, role, of, 'PC-1', in, 'AR', signaling])]). relacion([sujeto([pylori, infection, could]), verbo([promote]), complemento([gastric, cancer, by, regulating, lncRNAs, expression])]). relacion([sujeto(['Differentially']), verbo([expressed]), complemento([lncRNAs, between, 'H'])]). relacion([sujeto([pylori, positive, tissues]), verbo([have]), complemento([a, specific, profile, of, lncRNAs])]). relacion([sujeto(['We', identified, an, 'lncRNA-AF147447']), verbo([decreased]), complemento([expressed, by, 'H'])]). relacion([sujeto([pylori, 'infection,', which, can]), verbo([inhibit]), complemento(['GC', proliferation, and, invasion, in, vitro, and, in, 'vivo,', act, as, a, tumor, suppressor, in, the, development, of, 'H'])]). relacion([sujeto([pylori]), verbo([induced]), complemento(['GC'])]). relacion([sujeto(['LncRNA', 'AF147447', could, repress, 'MUC2', expression, by, direct]), verbo([binding]), complemento([or, increasing, 'miR-34c', expression])]). relacion([sujeto(['We', also]), verbo([found]), complemento([that, transcription, factor, 'E2F1', could, be, recruited, to, lncRNA, 'AF147447', promoter, by, 'RNA', immunoprecipatation, and, 'RNA', pull, down, assays])]). relacion([sujeto([pylori, infection, and]), verbo([provides]), complemento([a, rationale, for, the, potential, development, of, 'lncRNA-based', targeted, approaches, for, the, treatment, of, 'H'])]). relacion([sujeto(['In', the, last, 'years,', the, number, of, studies, describing, the, effect, of, both, polyphenols, against, cancer]), verbo([has]), complemento(['increased;', 'however,', the, mechanism, of, action, in, all, of, those, cases, is, not, completely, comprehended])]). relacion([sujeto(['Herein,', we, analyzed, the, anticancer, activity, of, resveratrol, and, curcumin]), verbo([reported]), complemento([in, the, literature, in, the, last, 11, 'years,', in, order, to, unravel, the, molecular, mechanism, of, action, of, both, compounds])]). relacion([sujeto(['Molecular']), verbo([targets]), complemento([and, cellular, pathways, will, be, described])]). relacion([sujeto(['Furthermore,', we, also, discussed, the, ability, of, these, natural, products]), verbo([act]), complemento([as, chemopreventive, and, its, use, in, association, with, other, anticancer, drugs])]). relacion([sujeto(['Diabetes', is, strongly]), verbo([associated]), complemento([with, systemic, inflammation, and, oxidative, 'stress,', but, its, effect, on, pulmonary, vascular, disease, and, lung, function, has, often, been, disregarded])]). relacion([sujeto(['While', microvascular, dysfunction, is, a, 'well-known', complication, of, 'diabetes,', the, mechanisms]), verbo([leading]), complemento([to, 'diabetes-induced', lung, injury, have, largely, been, disregarded])]). relacion([sujeto(['We', described, the, potential, involvement, of, 'diabetes-induced', 'platelet-endothelial', interactions, in, perpetuating, vascular, inflammation, and, oxidative, injury]), verbo([leading]), complemento([to, fibrotic, changes, in, the, lung])]). relacion([sujeto(['Changes', in, nitric, oxide, synthase, '(', 'NOS)', activation, and]), verbo([decreased]), complemento(['NO', bioavailability, in, the, diabetic, lung, increase, platelet, activation, and, vascular, injury, and, may, account, for, platelet, hyperreactivity, reported, in, diabetic, patients])]). relacion([sujeto(['Additionally,', the, 'Janus', 'kinase/signal', transducer, and, activator, of, transcription, '(', 'JAK/STAT)', pathway]), verbo([has]), complemento([been, reported, to, mediate, pancreatic, islet, 'damage,', and, is, implicated, in, the, onset, of, 'diabetes,', inflammation, and, vascular, injury])]). relacion([sujeto(['Many', growth, factors, and, 'diabetes-induced', agonists]), verbo([act]), complemento([via, the, 'JAK/STAT', pathway])]). relacion([sujeto(['Other', studies]), verbo([reported]), complemento([the, contribution, of, the, 'JAK/STAT', pathway, to, the, regulation, of, the, pulmonary, fibrotic, process, but, the, role, of, this, pathway, in, the, development, of, diabetic, lung, fibrosis, has, not, been, considered])]). relacion([sujeto(['These', observations, may, open, new, therapeutic, perspectives, for]), verbo([modulating]), complemento([multiple, pathways, to, mitigate, diabetes, onset, or, its, pulmonary, consequences])]). relacion([sujeto(['Viperin', is, an, endoplasmic, 'reticulum-associated', antiviral, responsive, 'protein,', which, is, highly, up]), verbo([regulated]), complemento([in, eukaryotic, cells, upon, viral, infection, through, both, 'interferon-dependent', and, independent, pathways])]). relacion([sujeto(['We']), verbo([have]), complemento([investigated, the, interaction, of, viperin, with, its, most, firmly, established, cellular, 'target,', farnesyl, pyrophosphate, synthase, '(', 'FPPS)'])]). relacion([sujeto(['Numerous', enveloped, viruses, utilize, 'cholesterol-rich', lipid, rafts, to, bud, from, the, host, cell, membrane, and, it, is, thought, that, by]), verbo([inhibiting]), complemento(['FPPS', activity, '(', and, therefore, cholesterol, 'synthesis),', viperin, retards, viral, budding, from, infected, cells])]). relacion([sujeto(['We', demonstrate, 'that,', consistent, with, this, 'hypothesis,', 'over-expression', of, viperin, in, human, embryonic, kidney, cells, reduces, the, intracellular, rate, of, accumulation, of, 'FPPS,', but, does, not]), verbo([inhibit]), complemento([or, inactivate, 'FPPS'])]). relacion([sujeto(['The', endoplasmic, 'reticulum-localizing,', 'N-terminal', amphipathic, helix, of, viperin, is, specifically]), verbo([required]), complemento([for, viperin, to, reduce, cellular, 'FPPS', levels])]). relacion([sujeto(['These', observations, imply, that, viperin, does, not]), verbo([act]), complemento([as, a, radical, 'SAM', enzyme, in, regulating, 'FPPS'])]). relacion([sujeto(['The', small, molecule, 'metal-ion', chelators, bipyridine, and, terpyridine, complexed, with, 'Zn(2+)', '(', 'ZnBip', and, 'ZnTerp)']), verbo([act]), complemento([as, 'CCR5', agonists, and, strong, positive, allosteric, modulators, of, 'CCL3-binding', to, 'CCR5,', weak, modulators, of, 'CCL4-binding,', and, as, competitors, for, 'CCL5-binding'])]). relacion([sujeto(['Here', we, describe, their]), verbo([binding]), complemento([site, using, computational, 'modeling,', binding, and, functional, studies, on, 'WT', and, mutated, 'CCR5'])]). relacion([sujeto([39, ')', 'Both', chelators]), verbo([interact]), complemento([with, aromatic, residues, in, the, transmembrane, receptor, domain])]). relacion([sujeto(['The', additional, pyridine, ring, of, 'ZnTerp']), verbo([binds]), complemento([deeply, in, the, major, binding, pocket, 'and,', in, contrast, to, 'ZnBip,', interacts, directly, with, the, 'W248(VI:13/6'])]). relacion([sujeto(['The', impact, of, 'W248', was, further, confirmed, by, 'ZnClTerp,', a, 'chloro-substituted', version, of, 'ZnTerp', that, showed, no, inherent, 'agonism,', but]), verbo([maintained]), complemento([positive, allosteric, modulation, of, 'CCL3-binding'])]). relacion([sujeto(['Despite', a, similar, overall]), verbo([binding]), complemento([mode, of, all, three, 'metal-ion', chelator, 'complexes,', the, 'pyridine-ring', of, 'ZnClTerp', blocks, the, conformational, switch, of, 'W248', required, for, receptor, 'activation,', explaining, its, lack, of, activity])]). relacion([sujeto(['Binding', studies, with, 125, 'I-CCL3', revealed, an, allosteric, interface, between, the, chemokine, and, the, small, molecule]), verbo([binding]), complemento([site, including, residues, 'Y37(I:07/1'])]). relacion([sujeto(['This', study]), verbo([provides]), complemento([new, insight, into, the, molecular, mechanism, of, 'CCR5', activation, and, paves, the, way, for, future, allosteric, drugs, for, chemokine, receptors])]). relacion([sujeto(['We', hypothesized, that, the, 'EMD', algorithm]), verbo([provides]), complemento([a, suitable, platform, for, decomposing, the, 'EMG', signal, into, physically, meaningful, intrinsic, mode, functions, '(', 'IMFs)', which, can, be, further, used, to, isolate, electrical, stimulation, '(', 'ES)', artifact])]). relacion([sujeto(['The', data, driven, nature, of, 'EMD', algorithm, and, its, ability, to]), verbo([act]), complemento([as, a, filter, bank, at, different, bandwidths, make, this, method, extremely, suitable, for, dissecting, 'ES', induced, 'EMG', into, 'IMFs'])]). relacion([sujeto(['This', study]), verbo([provides]), complemento([a, unique, approach, to, dissect, and, interpret, the, 'EMG', signal, during, 'FES', applications])]). relacion([sujeto(['The', purpose, of, this, paper, is, to, show, how, middle, managers, create, 'inter-organizational', change, by, doing, boundary, 'work:', the, dual]), verbo([act]), complemento([of, redrawing, boundaries, and, coordinating, work, in, new, ways])]). relacion([sujeto(['Empirically,', the, paper, is, based, on, an, ethnographic, investigation, of, middle, managers, that]), verbo([participate]), complemento([in, a, 'Dutch', reform, program, across, 'health,', social, 'care,', and, housing])]). relacion([sujeto(['They', use, boundary, objects, and, a, 'boundary-transcending', vocabulary, emphasizing, the, need, for, societal]), verbo([gains]), complemento([that, go, beyond, production, targets, of, individual, organizations])]). relacion([sujeto(['Culturally', 'appropriate,', innovative, strategies, to]), verbo([increase]), complemento([physical, activity, '(', 'PA)', in, women, of, color, are, needed])]). relacion([sujeto(['This', study, examined, whether, participation, in, 'SALSA,', an, 8, -, week, 'randomized,', crossover, pilot, study, to]), verbo([promote]), complemento(['PA,', led, to, improved, psychosocial, outcomes, and, whether, these, changes, were, associated, with, changes, in, 'PA', over, time])]). relacion([sujeto(['Women']), verbo([reported]), complemento([high, socioeconomic, status, and, decreases, in, exercise, 'self-efficacy', and, increases, in, motivational, readiness, for, exercise, and, number, of, stressful, events, '(', 'p<'])]). relacion([sujeto(['Changes', in, psychosocial, factors, were]), verbo([associated]), complemento([with, increases, in, 'PA'])]). relacion([sujeto(['Future', studies, are, needed, to, determine, whether, 'Latin', dance, improves, other, psychological, measures, and, quality, of, life, in, women, of, color, in, an, effort, to]), verbo([increase]), complemento(['PA', and, reduce, health, disparities])]). relacion([sujeto(['This', secondary, data, analyses, of, a, longitudinal, study, assessed, whether, 'self-efficacy', for, exercise, '(', 'SEE)']), verbo([mediated]), complemento([an, online, intervention, effects, on, exercise, among, older, adults, and, whether, age, '(', 50, -, 64, vs])]). relacion([sujeto(['Parallel', process, latent, growth, curve, modeling, '(', 'LGCM)', was, used, to, jointly, model, growths, in, 'SEE', and, in, exercise, and, to, assess, the]), verbo([mediating]), complemento([effect, of, 'SEE', on, the, effect, of, intervention, on, exercise])]). relacion([sujeto(['After', 'walking,', group, 'B', had, significant, reductions, in, 'dominant-side', ankle, joint, range, of, motion, and, 'power,']), verbo([suggesting]), complemento(['lower-leg', muscle, 'fatigue,', which, appeared, to, be, compensated, by, significantly, increased, 'non-dominant', side, knee, and, hip, motions])]). relacion([sujeto(['The', 6, 'MWT', was]), verbo([associated]), complemento([with, muscle, power, at, 50, '%', 1, 'RMQF', '(', r, =, 0.4, ;, 'P', =, 0.013, ')', but, not, muscle, power, at, 70, '%', 1, 'RMQF', '(', r, =, 0.24, ;, 'P', =, 0.15, ')', or, 1, 'RMQF', '(', r, =, 0.13, ;, 'P', =, 0.44, ')'])]). relacion([sujeto(['Lower', limb, muscle, power, is]), verbo([associated]), complemento([with, the, 6, 'MWT', and, 'light-intensity', activities, in, older, men, with, 'COPD'])]). relacion([sujeto(['The', 'FAT1', gene, is]), verbo([involved]), complemento([in, some, 'cancers;', 'however,', its, role, in, medulloblastoma, is, less, clear])]). relacion([sujeto(['Low', 'FAT1', expression, was]), verbo([associated]), complemento([with, poor, prognosis, in, children, with, medulloblastoma])]). relacion([sujeto(['Furthermore,', 'FAT1', may]), verbo([act]), complemento([on, 'Wnt', signaling, pathway, to, exert, its, antitumor, effect])]). relacion([sujeto(['In', many, 'respects,', employers, are, well, positioned, to, take, a]), verbo([leading]), complemento([role, in, helping, create, a, culture, of, health])]). relacion([sujeto(['Employers']), verbo([have]), complemento([access, to, many, programs, that, could, be, beneficial, to, their, 'employees\'', health])]). relacion([sujeto(['The', potential, for, financial]), verbo([gains]), complemento([related, to, health, improvement, may, motivate, employers, to, offer, these, 'programs,', and, if, the, gains, are, 'realized,', they, may, help, finance, the, programs])]). relacion([sujeto(['Enthusiasm', about, the, financial, and, health]), verbo([gains]), complemento([that, wellness, programs, might, yield, coexists, with, concerns, about, health, costs, shouldered, by, 'employees,', the, possibility, of, employment, 'discrimination,', and, the, potential, for, 'employers\'', invasion, of, 'employees\'', privacy])]). relacion([sujeto(['A', fragmented, regulatory, 'regime,', including, a, recently, issued, final, rule, under, the, 'Americans', with, 'Disabilities', 'Act,']), verbo([has]), complemento([been, created, to, address, these, concerns])]). relacion([sujeto(['New', care, delivery, models, that, hold, providers, more, accountable, for, 'coordinated,', 'high-quality', care, and, the, overall, health, of, their, patients]), verbo([have]), complemento([appeared, in, the, 'US', health, care, 'system,', spurred, by, recent, legislation, such, as, the, 'Affordable', 'Care', 'Act'])]). relacion([sujeto(['These', models, support, the, integration, of, health, care, 'systems,', but, maximizing, health, and, 'well-being', for, all, individuals, will]), verbo([require]), complemento([a, broader, conceptualization, of, health, and, more, explicit, connections, between, diverse, partners])]). relacion([sujeto(['This', 'Action', 'Area', conceives, of, a, strengthened, health, care, system, as, one, in, which, medical, 'care,', public, 'health,', and, social, services]), verbo([interact]), complemento([to, produce, a, more, 'effective,', 'equitable,', 'higher-value', whole, that, maximizes, the, production, of, health, and, 'well-being', for, all, individuals])]). relacion([sujeto(['VirF,', an, 'AraC-like', 'activator,', is]), verbo([required]), complemento([to, trigger, a, regulatory, cascade, that, initiates, the, invasive, program, of, 'Shigella', spp])]). relacion([sujeto(['VirF', expression, is]), verbo([activated]), complemento([upon, entry, into, the, host, and, depends, on, many, environmental, signals])]). relacion([sujeto(['Here,', we, show, that, the, virF, mRNA, is]), verbo([translated]), complemento([into, two, 'proteins,', the, major, 'form,', 'VirF30', '(', 30, &, 'nbsp;kDa),', and, the, shorter, 'VirF21', '(', 21, &, 'nbsp;kDa),', lacking, the, 'N-terminal', segment])]). relacion([sujeto(['Interestingly,', in, vitro, and, in, vivo, translation, experiments, showed, that, 'VirF21', is, also]), verbo([translated]), complemento([from, a, leaderless, mRNA, '(', 'llmRNA)', whose, 5, '\'', end, is, at, position, +, 309, /, +, 310, ',', only, 1, or, 2, nucleotides, upstream, of, the, 'ATG84', start, codon, of, 'VirF21', 'The', llmRNA, is, transcribed, from, a, 'gene-internal', 'promoter,', which, we, identified, here])]). relacion([sujeto(['Since', 'VirF21']), verbo([modulates]), complemento([the, intracellular, 'VirF', 'levels,', this, suggests, that, transcription, of, the, llmRNA, might, occur, when, the, onset, of, the, virulence, program, is, not, required])]). relacion([sujeto(['We', speculate, that, environmental, 'cues,', like, stress, 'conditions,', may]), verbo([promote]), complemento([changes, in, virF, mRNA, transcription, and, preferential, translation, of, llmRNA])]). relacion([sujeto([are, a, major]), verbo([cause]), complemento([of, dysentery, in, humans])]). relacion([sujeto(['In', bacteria, of, this, 'genus,', the, activation, of, the, invasive, program]), verbo([involves]), complemento([a, multitude, of, signals, that, act, on, all, layers, of, the, gene, regulatory, hierarchy])]). relacion([sujeto(['The', major, 'form,', 'VirF30,']), verbo([activates]), complemento([the, genes, necessary, for, 'virulence,', whereas, the, minor, 'VirF21,', which, shares, the, 'C-terminal', 'two-thirds', of, 'VirF30,', negatively, autoregulates, virF, expression, itself])]). relacion([sujeto(['VirF21', is]), verbo([transcribed]), complemento([from, a, newly, identified, 'gene-internal', promoter, 'and,', 'moreover,', is, translated, from, an, unusual, leaderless, mRNA])]). relacion([sujeto(['Piroxicam']), verbo([has]), complemento([been, reported, to, be, convertible, to, central, nervous, system, '(', 'CNS)', acting, agents])]). relacion([sujeto(['It']), verbo([has]), complemento([serious, depressant, effects, at, high, doses])]). relacion([sujeto(['Structural', barbituric, 'compounds,', 'carboxamide,', 'cyclohydrated,', benzothiazone, and, carboxybenzothiazone, metabolites, which, may]), verbo([act]), complemento([via, dopamine, and, adrenergic, receptors, causing, depression, of, 'CNS', activities])]). relacion([sujeto(['The', periodontal, therapies, along, with, systemic, antibiotic, therapy, aim, at, eliminating, the, subgingival, microbiota, to]), verbo([arrest]), complemento([the, progression, of, periodontal, diseases])]). relacion([sujeto(['The', objectives, of, the, study, are, to, develop, in, situ, thermoreversible, gelling, system, of, green, tea, catechins, suitable, for, periodontal, pocket, 'administration,', which, would]), verbo([act]), complemento([as, an, adjunct, to, mechanical, periodontal, therapy])]). relacion([sujeto(['In', vitro, drug]), verbo([release]), complemento([pattern, is, observed, through, spectrophotometer, analysis, at, 277, nm])]). relacion([sujeto(['Release', pattern, studies, showed, a, complete]), verbo([release]), complemento([of, drug, from, gel, occurred, by, 36, h])]). relacion([sujeto(['A', volume, of, 1.25, 'mg/ml', was, determined, as, 'MIC']), verbo([required]), complemento([against, the, periodontal, pathogens])]). relacion([sujeto(['Pluronic', gel, proved, to, be, a, promising, carrier, for, prolong, and, effective]), verbo([release]), complemento([of, green, tea, catechin])]). relacion([sujeto(['These', defects, resulting, from, tumor, 'excisions,', if, left, 'untreated,', will]), verbo([cause]), complemento([additional, problems, related, to, interposed, scar, and, collapse, of, lip, and, nose])]). relacion([sujeto(['This', study, describes, the, treatment, of, such, a, defect, resulting, from, a, myxoma, 'excision,', with, trifocal, distraction]), verbo([requiring]), complemento([only, one, additional, surgery])]). relacion([sujeto(['This', was, accomplished, by, internal, fixation, of, one, side, and, central, fixation, of, a, 'full-open', distractor, to]), verbo([act]), complemento([as, compression, device, when, reversely, activated])]). relacion([sujeto(['Long', noncoding, 'RNAs', '(', 'lncRNAs)', are, a, class, of, ubiquitous, noncoding, 'RNAs', and]), verbo([have]), complemento([been, found, to, act, as, tumor, suppressors, or, 'oncogenes,', which, dramatically, altered, our, understanding, of, cancer])]). relacion([sujeto(['In', this, 'study,', we]), verbo([provide]), complemento([the, first, comprehensive, 'genome-wide', analysis, of, 'NMR', lncRNAs, and, their, possible, associations, with, cancer, resistance])]). relacion([sujeto(['Our', results]), verbo([suggest]), complemento([that, lncRNAs, may, have, important, effects, on, anticancer, mechanism, in, 'NMR'])]). relacion([sujeto(['Due', to, the, impending, depletion, of, fossil, 'fuels,', it]), verbo([has]), complemento([become, important, to, identify, alternative, energy, sources])]). relacion([sujeto(['The', biofuel, industry]), verbo([has]), complemento([proven, to, be, a, promising, alternative])]). relacion([sujeto(['The', 'copper-dependent', 'Auxiliary', 'Activity', family, 9, '(', 'AA9)', proteins]), verbo([have]), complemento([been, found, to, act, synergistically, with, other, 'cellulose-degrading', enzymes, resulting, in, an, increased, rate, of, cellulose, breakdown])]). relacion([sujeto(['As', 'AA9', proteins, are, known, to, exhibit, low, sequence, 'conservation,', the, analysis, of, unique, features, of, 'AA9', domains, of, these, enzymes, should]), verbo([provide]), complemento([insights, for, the, better, understanding, of, how, different, 'AA9', 'PMO', types, function])]). relacion([sujeto(['These', highly, variable, proteins, were]), verbo([found]), complemento([to, have, a, greater, degree, of, conservation, within, their, respective, types])]). relacion([sujeto(['This']), verbo([provides]), complemento([a, basis, under, which, to, identify, and, group, new, 'AA9', 'LPMOs', in, future])]). relacion([sujeto([')']), verbo([has]), complemento([one, of, the, largest, genomes, among, cereal, crops, and, repetitive, sequences, account, for, over, 90, '%', of, its, length])]). relacion([sujeto(['In', total, 515, 'DArT', sequences, could, be, incorporated, into, publicly, available, rye, genome, zippers]), verbo([providing]), complemento([a, starting, point, for, the, integration, of, 'DArT-', and, 'transcript-based', genomics, resources, in, rye])]). relacion([sujeto(['Using', 'Blast2Go', pipeline, we, attributed, putative, gene, functions, to, 1101, '(', 29.4, '%', ')', of, the, 'non-redundant', 'DArT', marker, 'sequences,', including, 132, sequences, with, putative, disease, 'resistance-related', 'functions,', which, were]), verbo([found]), complemento([to, be, preferentially, located, in, the, 4, 'RL', and, 6, 'RL', chromosomes])]). relacion([sujeto(['Obtained', data, demonstrate, that, 'DArT', markers, effectively]), verbo([target]), complemento([gene, space, in, the, 'large,', 'complex,', and, repetitive, rye, genome])]). relacion([sujeto(['Some', studies, show, that, a, decision, to]), verbo([act]), complemento([leads, to, greater, regret, than, a, decision, not, to, act, when, both, resulted, in, 'failure,', because, the, latter, is, usually, the, norm])]). relacion([sujeto(['We']), verbo([suggest]), complemento([that, the, decision, 'maker\'s', regulatory, 'focus,', affects, regret, after, action, or, inaction])]). relacion([sujeto(['Hence,', we, hypothesized, that, 'promotion-focused', individuals, will, feel, less, regret, than, 'prevention-focused', individuals, when, a, decision, to]), verbo([act]), complemento([ended, poorly])]). relacion([sujeto(['In', 'addition,', we, hypothesized, that, a]), verbo([trigger]), complemento([for, change, implied, in, the, 'situation,', decreases, the, level, of, regret, following, action])]). relacion([sujeto(['In', 'addition,', a]), verbo([trigger]), complemento([for, change, decreases, regret, following, action])]). relacion([sujeto(['Endogenous', neurosteroids, and, neuroactive, steroids]), verbo([have]), complemento([potent, and, widespread, actions, on, the, brain, via, inhibitory, 'GABAA', receptors])]). relacion([sujeto(['In', recombinant, receptors, and, genetic, mouse, models, their, actions, depend, on, the, 'α,', 'β,', and, δ, subunits, of, the, 'receptor,', especially, on, those, that, form, extrasynaptic, 'GABAA', receptors, responsible, for, 'non-synaptic', '(', 'tonic)', 'inhibition,', but, they, also]), verbo([act]), complemento([on, synaptically, enriched, γ2, 'subunit-containing', receptors, and, even, on, αβ, binary, receptors])]). relacion([sujeto(['Here', we, tested, whether, behavioral, sensitivity, to, the, neuroactive, steroid, agonist, 5, 'β-pregnan-3α-ol-20-one', is, altered, in, genetically, engineered, mouse, models, that]), verbo([have]), complemento([deficient, 'GABAA', 'receptor-mediated', synaptic, inhibition, in, selected, neuronal, populations])]). relacion([sujeto(['Motor-impairing', effects, of, 5, 'β-pregnan-3α-ol-20-one', were, strongly]), verbo([increased]), complemento([in, all, three, mouse, models, in, which, γ2, 'subunit-dependent', synaptic, 'GABAA', responses, in, cerebellar, neurons, were, genetically, abolished])]). relacion([sujeto(['The', results]), verbo([suggest]), complemento(['that,', when, the, deletion, of, γ2, subunit, has, removed, synaptic, 'GABAA', receptors, from, the, specific, cerebellar, neuronal, 'populations,', the, effects, of, neuroactive, steroids, solely, on, extrasynaptic, αβ, or, αβδ, receptors, lead, to, enhanced, changes, in, the, 'cerebellum-generated', behavior])]). relacion([sujeto(['Since', clinical, efficiency, is, not, satisfactory, and, the, established, drugs]), verbo([have]), complemento([massive, side, 'effects,', new, strategies, to, treat, 'IBD', are, required])]). relacion([sujeto(['A', 'pro-inflammatory', cytokine, cocktail, consisting, of, 'TNF-α,', 'IL-β,', and, 'IFN-γ', was, used, to, simulate, inflammatory, stimuli, normally]), verbo([caused]), complemento([by, immune, cells])]). relacion([sujeto(['Both,', 'STW5', and, 'STW5-II', did, not, show, any, effect, on, 'MAPK', 'p38,', but, were, effective, in, reducing]), verbo([phosphorylated]), complemento([levels, of, 'STAT1'])]). relacion([sujeto(['In', 'conclusion,', both, combination, preparations]), verbo([act]), complemento([in, an, 'anti-inflammatory', manner, by, influencing, cytokine, secretion, via, reduced, activity, of, the, 'JAK/STAT1', pathway])]). relacion([sujeto(['Relevant', differences, between, 'STW5', and, 'STW5-II', were, not]), verbo([found]), complemento([indicating, similar, efficacies])]). relacion([sujeto(['Changes']), verbo([involving]), complemento([the, health, care, economic, landscape, have, affected, 'physicians\'', 'workflow,', 'productivity,', compensation, 'structures,', and, culture])]). relacion([sujeto(['Ongoing', 'Federal', legislation, regarding, regulatory, documentation, and, imminent, 'payment-changing', methodologies]), verbo([have]), complemento([encouraged, physician, consolidation, into, larger, 'practices,', creating, affiliations, with, 'hospitals,', multidisciplinary, medical, 'specialties,', and, integrated, delivery, networks])]). relacion([sujeto(['As', subspecialization, and, evolution, of, care, models]), verbo([have]), complemento(['accelerated,', independent, medical, groups, have, broadened, ancillary, service, lines, by, investing, in, enterprises, that, compete, with, 'hospital-based', '(', academic, and, 'nonacademic)', 'entities,', as, well, as, 'non-physician-', owned, multispecialty, 'enterprises,', for, both, outpatient, and, inpatient, services])]). relacion([sujeto(['For', groups, that, can, implement, change, 'rapidly,', 'efficiently,', and, 'harmoniously,', there, will, be, opportunities, to, achieve, the, 'Triple', 'Aim', goals, of, the, 'Patient', 'Protection', and, 'Affordable', 'Care', 'Act,', while]), verbo([maintaining]), complemento([a, successful, 'medical-financial', practice])]). relacion([sujeto(['In', 'summary,', implementing, new, payment, algorithms, alongside, comprehensive, care, coordination, will, assist, urology, groups, in, addressing, the, health, economic, cost, and, quality, challenges, that]), verbo([have]), complemento([been, historically, encountered, with, 'fee-for-service', systems])]). relacion([sujeto(['In', 'response,', ancillary, services, and, patient, throughput, will, need, to, evolve, in, order, to, adequately, align, quality, measurement, and]), verbo([reporting]), complemento([systems, across, provider, footprints, and, patient, populations])]). relacion([sujeto(['We']), verbo([find]), complemento([a, highly, genetically, distinct, lineage, on, 'Cuba', which, we, describe, as, 'Argiope', butchkosp])]). relacion([sujeto(['While', the, argentata, lineage, seems, to, readily, balloon, shorter, 'distances,', stretches, of, ocean, still]), verbo([act]), complemento([as, filters, for, 'among-island', 'gene-flow', as, evidenced, by, distinct, haplotypes, on, the, more, isolated, 'islands,', high, 'F(ST)', 'values,', and, strong, correlation, between, intraspecific, '(', but, not, 'interspecific)', genetic, and, geographic, distances])]). relacion([sujeto(['Our', results, are, consistent, with, the, intermediate, dispersal, model]), verbo([suggesting]), complemento([that, good, 'dispersers,', such, as, our, study, 'species,', limit, the, effect, of, oceanic, barriers, and, thus, diversification, and, endemism])]). relacion([sujeto(['It']), verbo([provides]), complemento([a, legal, framework, for, the, 'regulation,', 'development,', and, management, of, 'Nigeria\'s', 'Health', 'System'])]). relacion([sujeto(['Although', health, professionals, in, 'Nigeria']), verbo([have]), complemento([good, awareness, and, perception, of, the, 'NHA', 2014, ',', their, knowledge, of, the, 'Act', is, poor])]). relacion([sujeto(['In', the, further, dealings, of, such, person, the, medical, officer, of, the, psychiatric, facility, comes, across, legal, 'terms,', which]), verbo([require]), complemento([understanding, so, that, patients, could, be, dealt, with, properly])]). relacion([sujeto(['There', are, many, times, when, the, relevant, section, under, which, the, admission, is, ordered, is, not]), verbo([found]), complemento([in, the, reception, order])]). relacion([sujeto(['They', were, administered, a, questionnaire, containing, these, terms, and, asked, to]), verbo([provide]), complemento([the, meaning, of, these, terms])]). relacion([sujeto(['Stephen', 'Napier']), verbo([has]), complemento([argued, against, the, soundness, of, what, he, calls, the, &, 'quot;Canon-Law', 'argument"', against, the, moral, permissibility, of, a, couple, employing, a, condom, for, the, sake, of, one, spouse, avoiding, the, contraction, of, 'HIV', from, the, other, spouse])]). relacion([sujeto(['Without', an, attempt, to]), verbo([provide]), complemento([a, full, defense, of, the, 'Canon-Law', argument, per, 'se,', this, paper, argues, that, 'Napier', has, not, shown, that, argument, to, be, inadequate])]). relacion([sujeto(['Using', magisterial, documents, and, canonical, 'sources,', this, paper]), verbo([suggests]), complemento([that, the, distinction, between, validity, and, liceity, can, be, usefully, applied, to, conjugal, acts])]). relacion([sujeto(['Lay', 'Summary:', 'Stephen', 'Napier']), verbo([has]), complemento([argued, in, favor, of, the, claim, that, there, is, no, plausible, argument, for, thinking, that, married, couples, who, use, a, condom, in, order, to, prevent, 'HIV', transmission, are, necessarily, doing, something, morally, wrong])]). relacion([sujeto(['In']), verbo([responding]), complemento([to, 'Napier', by, showing, that, his, arguments, in, favor, of, his, claim, are, 'inconclusive,', this, article, introduces, a, 'distinction,', frequently, used, in, sacramental, 'theology,', between, validity, and, liceity, '(', 'lawfulness)', and, applies, this, distinction, to, marital, actions])]). relacion([sujeto([&, 'quot;', 'Recent', studies]), verbo([have]), complemento([identified, that, levonorgestrel, administered, orally, in, emergency, contraception, '(', 'LNG-EC)', is, only, efficacious, when, taken, before, ovulation])]). relacion([sujeto(['However,', the, drug, does, not, consistently]), verbo([prevent]), complemento([follicular, rupture, or, impair, sperm, function])]). relacion([sujeto(['We', also, examine, the, available, evidence, to, determine, if, 'pre-ovulatory', drug, administration, may, be]), verbo([associated]), complemento([with, 'post-fertilization', effects])]). relacion([sujeto(['The', drug]), verbo([has]), complemento([no, ability, to, alter, sperm, function, at, doses, used, in, vivo, and, has, limited, ability, to, suppress, ovulation])]). relacion([sujeto(['Our', analysis, estimates, that, the, 'drug\'s', ovulatory, inhibition, potential, could]), verbo([prevent]), complemento([less, than, 15, percent, of, potential, 'conceptions,', thus, making, a, 'pre-fertilization', mechanism, of, action, significantly, less, likely, than, previously, thought])]). relacion([sujeto(['Luteal', effects, '(', such, as]), verbo([decreased]), complemento(['progesterone,', altered, glycodelin, 'levels,', and, shortened, luteal, 'phase)', present, in, the, literature, may, suggest, a, 'pre-ovulatory', induced, 'post-fertilization', drug, effect])]). relacion([sujeto(['The', drug, was, originally, thought, to, work, by]), verbo([preventing]), complemento([fertilization])]). relacion([sujeto(['Recent', research]), verbo([has]), complemento([cast, doubt, on, this])]). relacion([sujeto(['Our', review, of, the, research]), verbo([suggests]), complemento([that, it, could, act, in, a, 'pre-fertilization', 'capacity,', and, we, estimate, that, it, could, prevent, ovulation, in, only, 15, percent, or, less, of, cases])]). relacion([sujeto(['The', drug]), verbo([has]), complemento([no, ability, to, alter, sperm, function, and, limited, ability, to, suppress, ovulation])]). relacion([sujeto(['Further,', data]), verbo([suggest]), complemento([that, when, administered, 'pre-ovulation,', it, may, have, a, 'post-fertilization', 'MOA'])]). relacion([sujeto(['A', number, of, long, 'non-coding', 'RNAs', '(', 'lncRNAs)']), verbo([have]), complemento([been, found, to, play, critical, roles, in, oncogenesis, and, tumor, progression])]). relacion([sujeto(['We', aimed, to, investigate, whether, lncRNAs, could]), verbo([act]), complemento([as, prognostic, biomarkers, for, papillary, thyroid, cancer, '(', 'PTC)', that, may, assist, us, in, evaluating, disease, status, and, prognosis, for, patients])]). relacion([sujeto(['We']), verbo([found]), complemento([220, lncRNAs, with, expression, alteration, from, the, annotated, 2773, lncRNAs, approved, by, the, 'HUGO', gene, nomenclature, committee, in, 'The', 'Cancer', 'Genome', 'Atlas', '(', 'TCGA)', 'dataset,', of, which, 'FAM41C,', 'CTBP1-AS2,', 'LINC00271,', 'HAR1A,', 'LINC00310', and, 'HAS2-AS1', were, associated, with, recurrence])]). relacion([sujeto(['After', adjusting, classical, clinicopathogical, factors, and, 'BRAF(V600E)', 'mutation,', 'LINC00271', was]), verbo([found]), complemento([to, be, an, independent, risk, factor, for, extrathyroidal, 'extension,', lymph, node, 'metastasis,', advanced, tumor, stage, 'III/IV', and, recurrence, in, multivariate, analyses])]). relacion([sujeto(['The', 'Gene', 'Set', 'Enrichment', 'Analysis', '(', 'GSEA)', revealed, that, genes]), verbo([associated]), complemento([with, cell, adhesion, 'molecules,', cell, 'cycle,', 'P53', signaling, pathway, and, 'JAK/STAT', signaling, pathway, were, remarkably, enriched, in, 'lower-LINC00271', versus, 'higher-LINC00271', tumors])]). relacion([sujeto(['The', acrylate, and, 'BODIPY', moieties, in, probe, 3]), verbo([act]), complemento([as, a, reaction, site, and, reporter, 'group,', respectively])]). relacion([sujeto(['The', cleavage, reaction]), verbo([induced]), complemento([by, cysteine, leads, to, acrylate, 'hydrolysis,', and, thereby, triggers, 'PET', 'on,', which, effectively, quench, the, fluorescence, of, 3])]). relacion([sujeto(['Theobromine', works, as, a, phosphodiesterase, '(', 'PDE)', inhibitor, to]), verbo([increase]), complemento([intracellular, cyclic, adenosine, monophosphate, '(', 'cAMP)'])]). relacion([sujeto([cAMP]), verbo([activates]), complemento([the, 'cAMP-response', 'element-binding', protein, '(', 'CREB),', which, is, involved, in, a, large, variety, of, brain, 'processes,', including, the, induction, of, the, 'brain-derived', neurotrophic, factor, '(', 'BDNF)'])]). relacion([sujeto(['Here,', we, investigated, whether, orally, administered, theobromine, could]), verbo([act]), complemento([as, a, 'PDE', inhibitor, centrally, and, affect, 'cAMP/CREB/BDNF', pathways, and, learning, behavior, in, mice])]). relacion([sujeto(['We', measured, the, levels, of, 'theobromine,']), verbo([phosphorylated]), complemento(['vasodilator-stimulated', phosphoprotein, '(', 'p-VASP),', phosphorylated, 'CREB', '(', 'p-CREB),', and, 'BDNF', in, the, brain])]). relacion([sujeto(['These', results, strongly]), verbo([suggested]), complemento([that, orally, administered, theobromine, acted, as, a, 'PDE', inhibitor, in, the, 'brain,', and, it, augmented, the, 'cAMP/CREB/BDNF', pathways, and, motor, learning, in, mice])]). relacion([sujeto(['Particular', neutralizing, monoclonal, antibodies, to, certain, cytokines]), verbo([act]), complemento([as, agonists, in, vivo, by, protection, of, the, 'cytokine\'s', active, site, and, prolongation, of, cytokine, 'half-life'])]). relacion([sujeto(['While', this, principle, might, be, useful, for]), verbo([targeted]), complemento(['immunotherapy,', its, role, in, the, pathogenesis, of, inflammation, and, autoimmunity, is, unclear])]). relacion([sujeto(['We', sought, to, determine, whether, 'slight,', structurally, 'non-relevant', modifications, of, the, prototypic, 'pro-inflammatory', cytokine, 'interleukin-1β', '(', 'IL-1β)', during, an, immune, response, could, elicit, polyclonal, 'anti-IL-1β', antibody, responses, that]), verbo([modulated]), complemento(['IL-1β\'s', in, vivo, activity])]). relacion([sujeto(['While', antibody, responses, generated, to, one, variant, were, potently]), verbo([inhibiting]), complemento(['IL-1β,', antibody, responses, induced, by, the, other, variant, even, potentiated, the, in, vivo, effects, of, 'IL-1β;', the, latter, led, to, enhanced, morbidity, in, two, different, 'IL-1β-mediated', mouse, 'models,', including, a, model, of, inflammatory, bowel, disease, and, an, inflammatory, arthritis, model])]). relacion([sujeto(['These', data, demonstrate, that, endogenous, polyclonal, 'anti-cytokine', antibody, responses, can]), verbo([enhance]), complemento([the, 'cytokine\'s', activity, in, inflammatory, and, autoimmune, diseases])]). relacion([sujeto(['Ca(2+),', in, the, absence, of, 'ATP,', was]), verbo([required]), complemento([for, engulfment, of, 'E'])]). relacion([sujeto(['Adding', 'ATP']), verbo([inhibited]), complemento([phagocytosis, of, 'S'])]). relacion([sujeto([&, 'nbsp;coli', regardless, of, 'Ca(2+),']), verbo([suggesting]), complemento([that, 'Ca(2+)', entry, was, not, important, for, inhibiting, phagocytosis])]). relacion([sujeto([&, 'nbsp;glabrata', mutants, had, an, absolute, requirement, for, extracellular, 'Ca(2+)', due, to, yeast, adhesion, to, macrophages]), verbo([mediated]), complemento([by, 'Ca(2+)-dependent', adhesion, proteins])]). relacion([sujeto(['We', conclude, that, unstimulated, 'P2X7', from, 'J774 cells']), verbo([act]), complemento([as, scavenger, receptor, for, the, uptake, of, 'S'])]). relacion([sujeto([&, 'nbsp;glabrata', phagocytosis, was]), verbo([mediated]), complemento([by, the, adhesins, 'Epa1,', 'Epa6', and, 'Epa7'])]). relacion([sujeto(['Hypoxia-inducible', factor, prolyl, 4, -, hydroxylases, '(', 'HIF-P4Hs,', also, called, 'PHDs', and, 'EglNs)', are, enzymes, that]), verbo([act]), complemento([as, cellular, oxygen, sensors])]). relacion([sujeto(['HIF-P4Hs', can, be]), verbo([targeted]), complemento([with, small, molecule, 'inhibitors,', which, stabilize, 'HIF', under, normoxia, and, initiate, the, hypoxia, response])]). relacion([sujeto(['Such', inhibitors, are, in, phase, 2, and, 3, clinical, trials, for, the, treatment, of, anemia, due, to, their, ability, to]), verbo([induce]), complemento([erythropoietin, and, iron, metabolism, genes])]). relacion([sujeto(['Recent', data]), verbo([suggest]), complemento([that, 'HIF-P4H', inhibition, has, a, therapeutic, role, beyond, anemia, in, cardiac, 'ischemia,', obesity, and, metabolic, 'dysfunction,', and, atherosclerosis])]). relacion([sujeto(['The', molecular, level, mechanisms]), verbo([involved]), complemento([are, 'HIF', stabilization, driven, changes, in, gene, expression, that, improve, perfusion, and, endothelial, 'function,', reprogram, metabolism, to, promote, glucose, intake, and, glycolysis, over, oxidative, 'metabolism,', reduce, inflammation, and, beneficially, modify, innate, immune, system])]). relacion([sujeto(['The', principal, mechanism, by, which, bronchodilator, 'β-adrenoceptor', agonists]), verbo([act]), complemento([is, to, relax, airways, smooth, muscle, although, they, may, also, be, 'anti-inflammatory'])]). relacion([sujeto(['The', purpose, of, this, study, was, to, evaluate, whether, 'β-adrenoceptor', agonists]), verbo([prevent]), complemento(['pro-inflammatory', cytokine, generation, from, activated, human, lung, macrophages])]). relacion([sujeto(['The', cells, were, 'pre-treated', with, both, 'short-acting', '(', 'isoprenaline,', 'salbutamol,', 'terbutaline)', and, 'long-acting', '(', 'formoterol,', 'salmeterol,', 'indacaterol)', 'β-agonists', before, activation, with, lipopolysaccharide, '(', 'LPS)', to]), verbo([induce]), complemento([cytokine, '(', 'TNFα,', 'IL-6,', 'IL-8', and, 'IL-10)', generation])]). relacion([sujeto(['Further', experiments, using, the, 'β2-adrenoceptor', antagonist, 'ICI-118,551']), verbo([suggested]), complemento([that, the, effects, of, indacaterol, were, likely, to, be, mediated, by, 'β2-adrenoceptors', whereas, those, of, salmeterol, were, not])]). relacion([sujeto(['Extremely', hazardous, substances, can, be]), verbo([released]), complemento([accidentally, as, a, result, of, chemical, 'spills,', industrial, 'explosions,', 'fires,', or, accidents, involving, railroad, cars, and, trucks, transporting, 'EHSs'])]). relacion([sujeto(['Workers', and, residents, in, communities, surrounding, industrial, facilities, where, these, substances, are, 'manufactured,', 'used,', or, stored, and, in, communities, along, the, 'nation\'s', railways, and, highways, are, potentially, at, risk, of, being, exposed, to, airborne, 'EHSs', during, accidental]), verbo([releases]), complemento([or, intentional, releases, by, terrorists])]). relacion([sujeto(['Environmental', 'Protection', 'Agency', '(', 'EPA)']), verbo([has]), complemento([identified, approximately, 400, 'EHSs', on, the, basis, of, acute, lethality, data, in, rodents])]). relacion([sujeto(['This']), verbo([report]), complemento([will, inform, 'planning,', 'response,', and, prevention, in, the, 'community,', the, 'workplace,', 'transportation,', the, 'military,', and, the, remediation, of, 'Superfund', sites])]). relacion([sujeto(['Carbapenems', are, 'beta-lactam', antibiotics, with, a, very, broad, spectrum, of, activity, and]), verbo([act]), complemento([by, disrupting, the, synthesis, of, bacterial, cell, walls])]). relacion([sujeto(['In', 'contrast,', 'beta-lactamase', inhibitors]), verbo([have]), complemento([little, antibacterial, activity, alone])]). relacion([sujeto(['When', used, with, 'beta-lactams', 'however,', the, combination, therapy]), verbo([provides]), complemento([enhanced, and, extended, spectrum, of, activity, against, bacteria, containing, 'plasmid-mediated', and, chromosomal, 'beta-lactamases'])]). relacion([sujeto(['The', growing, problem, of, 'multi-drug', resistance, '(', 'MDR)', worldwide]), verbo([has]), complemento([led, to, efforts, in, restricting, the, use, of, carbapenems])]). relacion([sujeto(['MDR', and, 'gram-negative', bacterial, infections, are, especially, predominant, in, febrile, neutropenia, '(', 'FN),', where, over, 50, '%', of, patients]), verbo([have]), complemento([an, established, or, occult, 'infection,', and, over, 20, '%', have, bacteremia])]). relacion([sujeto(['The', purpose, of, this]), verbo([report]), complemento([is, to, review, 'evidence-based', guidelines, on, the, appropriate, indications, or, circumstances, for, the, use, of, carbapenems, and, other, empiric, therapies, in, the, context, of, 'MDR', infections, and, 'FN'])]). relacion([sujeto(['Symptoms']), verbo([associated]), complemento([with, mania, can, include, increased, creativity, and, 'productivity;', 'however,', mania, can, also, lead, to, immediate, hospitalization, or, involuntary, committal, under, the, 'Mental', 'Health', 'Act'])]). relacion([sujeto(['Symptoms']), verbo([associated]), complemento([with, depression, can, lead, to, increased, rates, of, suicide, and, suicide, ideation])]). relacion([sujeto(['First', generation, antipsychotics, mitigate, bipolar, disorder, symptoms, by, antagonizing, dopamine, 'D2', 'receptors,', while, second, generation, antipsychotics]), verbo([have]), complemento([an, affinity, for, serotonin, 5, -, hydroxytryptamine, receptors, and, adrenergic, receptors, in, addition, to, being, 'D2', receptor, antagonists])]). relacion([sujeto(['Although', combinations, of, atypical, antipsychotics]), verbo([have]), complemento([been, used, for, the, treatment, of, other, 'disorders,', such, as, 'schizophrenia,', the, effectiveness, of, combination, therapy, in, bipolar, disorder, is, unclear])]). relacion([sujeto(['This', 'Rapid', 'Response']), verbo([report]), complemento([aims, to, review, the, clinical, and, 'cost-effectiveness', of, combination, atypical, antipsychotics, in, adolescents, or, adults, with, bipolar, disorder, with, psychotic, features])]). relacion([sujeto(['Guidelines']), verbo([associated]), complemento([with, the, use, of, combination, atypical, antipsychotics, in, adolescents, or, adults, with, bipolar, disorder, with, psychotic, features, will, also, be, examined])]). relacion([sujeto(['Specific', payment, strategies, include, 'pay-for-performance', and, other, quality, incentive, programs, that, tie, financial, rewards, and, sanctions, to, the, quality, and, efficiency, of, care]), verbo([provided]), complemento([and, accountable, care, organizations, in, which, health, care, providers, are, held, accountable, for, both, the, quality, and, cost, of, the, care, they, deliver])]). relacion([sujeto(['Accounting', 'For', 'Social', 'Risk', 'Factors', in, 'Medicare', 'Payment:', 'Data', is, the, fourth, in, a, series, of, five, brief]), verbo([reports]), complemento([that, aim, to, inform, 'ASPE', analyses, that, account, for, social, risk, factors, in, 'Medicare', payment, programs, mandated, through, the, 'IMPACT', 'Act'])]). relacion([sujeto(['This']), verbo([report]), complemento([provides, guidance, on, data, sources, for, and, strategies, to, collect, data, on, indicators, of, social, risk, factors, that, could, be, accounted, for, 'Medicare', quality, measurement, and, payment, programs])]). relacion([sujeto(['MiRs', are]), verbo([involved]), complemento([in, regulation, of, several, processes, such, as, growth, and, 'development,', fuel, 'metabolism,', insulin, 'secretion,', immune, 'function,', miocardium, 'remodeling,', cell, 'proliferation,', 'differenciation,', 'survival,', and, death])]). relacion([sujeto(['These', molecules]), verbo([have]), complemento([also, been, proposed, to, be, potential, biomarkers, 'and/or', therapeutical, targets, in, 'obesity,', type, 2, diabetes, 'mellitus,', cardiovascular, 'diseases,', metabolic, 'syndrome,', and, cancer])]). relacion([sujeto(['MiRs', are]), verbo([released]), complemento([by, most, cells, and, potentially, act, on, intercellular, communication, to, borderer, or, distant, cells])]). relacion([sujeto(['Various', studies]), verbo([have]), complemento([been, performed, to, elucidate, the, involvement, of, miRs, in, 'exercise-induced', effects])]). relacion([sujeto(['The', state, of, the, art, and, the, perspectives, on, miRs]), verbo([associated]), complemento([with, physical, exercise, will, be, presented])]). relacion([sujeto(['Nicotine', replacement, therapy, '(', 'NRT)', is, a, common, 'first-line', treatment, to]), verbo([prevent]), complemento([nicotine, withdrawal, in, smokers])]). relacion([sujeto(['However,', available, literature]), verbo([reports]), complemento([conflicting, results, regarding, its, efficacy, and, safety, in, critically, ill, patients])]). relacion([sujeto(['The', use, of, 'NRT', to]), verbo([prevent]), complemento([nicotine, withdrawal, in, 'ICU', patients, is, associated, with, increased, use, of, antipsychotic, medication, and, physical, 'restraint,', and, with, prolonged, mechanical, ventilation])]). relacion([sujeto(['Despite', substantial, progress, in, the, last, two, 'decades,', limitations, due, to, 'financial,', 'infrastructural,', manpower, and, research, constraints]), verbo([act]), complemento([as, barriers, to, fulfilling, the, large, need, for, pediatric, 'HSCT', services, in, our, country])]). relacion([sujeto(['However,', the, role, of, the, attenuation, due, to, the, patient, table, in, these, estimations]), verbo([requires]), complemento([careful, consideration, and, is, the, subject, of, this, study])]). relacion([sujeto(['However,', a, pointing]), verbo([act]), complemento([is, often, misinterpreted, as, indicating, a, different, spatial, referent, position, than, intended, by, the, pointer])]). relacion([sujeto(['It']), verbo([has]), complemento([been, suggested, that, this, happens, because, pointers, put, the, tip, of, the, index, finger, close, to, the, line, joining, the, eye, to, the, referent])]). relacion([sujeto(['However,', the, person, interpreting, the, pointing]), verbo([act]), complemento([extrapolates, the, vector, defined, by, the, arm, and, index, finger])]). relacion([sujeto(['As', this, line, crosses, the, 'eye-referent', 'line,', it]), verbo([suggests]), complemento([a, different, referent, position, than, the, one, that, was, meant])]). relacion([sujeto(['In', 'Experiment', 1, ',', we, compared, naïve, 'pointer-observed', dyads, with, dyads, in, which, the, discrepancy, between, the, vectors, defining, the, production, and, interpretation, of, pointing]), verbo([acts]), complemento([has, been, reduced])]). relacion([sujeto(['Furthermore,', we]), verbo([suggest]), complemento([that, instructions, that, reduce, the, discrepancy, between, these, spatial, rules, can, improve, communicating, with, pointing, gestures])]). relacion([sujeto(['Smoking', control, policies, and, treatment, resources, for, smoking, cessation]), verbo([have]), complemento([advanced, in, recent, 'years,', showing, highly, satisfactory, 'results,', particularly, in, 'Brazil'])]). relacion([sujeto(['Therefore,', pulmonologists]), verbo([have]), complemento([a, very, promising, area, in, which, to, work, with, their, patients, and, the, general, population])]). relacion([sujeto(['We', must]), verbo([act]), complemento([with, greater, impetus, in, support, of, health, care, policies, and, social, living, standards, that, directly, contribute, to, improving, health, and, quality, of, life])]). relacion([sujeto(['In', this, 'respect,', pulmonologists, can, play, a, greater, role, as, they, get, more]), verbo([involved]), complemento([in, treating, 'smokers,', strengthening, 'anti-smoking', 'laws,', and, demanding, health, care, policies, related, to, lung, diseases])]). relacion([sujeto(['RESUMO', 'O', tabagismo, é, o, fator, de, risco, mais, prevenível, e, controlável, em, saúde, 'e,', por, 'isso,', precisa, ter, a, máxima, atenção, e]), verbo([ser]), complemento([muito, mais, enfocado, por, todos, os, profissionais, da, saúde])]). relacion([sujeto(['Entretanto,', ainda, resta, um, longo, caminho, a]), verbo([ser]), complemento([percorrido, para, que, se, possa, considerar, o, tabagismo, como, uma, doença, controlada, sob, o, ponto, de, vista, da, saúde, pública])]). relacion([sujeto(['Over', the, past, few, 'years,', significant, efforts]), verbo([have]), complemento([been, made, to, decrease, the, effects, of, drought, stress, on, plant, productivity, and, quality])]). relacion([sujeto(['Specifically,', 'FNPs', are, able, to, penetrate, plant, leaf, and, root, 'tissues,', where, they]), verbo([bind]), complemento([water, in, various, cell, compartments])]). relacion([sujeto(['This', hydroscopic, activity]), verbo([suggests]), complemento([that, 'FNPs', could, be, beneficial, in, plants])]). relacion([sujeto(['Drought', stress]), verbo([induced]), complemento([a, significant, increase, in, the, compatible, osmolyte, proline, in, both, the, leaves, and, roots, of, control, 'plants,', but, not, in, 'FNP', treated, plants])]). relacion([sujeto(['These', results, indicate, that, 'FNPs', could]), verbo([act]), complemento([as, intracellular, binders, of, 'water,', creating, an, additional, water, 'reserve,', and, enabling, adaptation, to, drought, stress])]). relacion([sujeto(['Moreover,', analysis, of, plant, antioxidant, enzyme, activities, '(', 'CAT,', 'APx', and, 'GPx),', 'MDA', and, 'GSH', content, indicate, that, fullerenol, foliar, application, could]), verbo([have]), complemento([some, beneficial, effect, on, alleviating, oxidative, effects, of, drought, 'stress,', depending, on, the, concentration, of, nanoparticles, applied])]). relacion([sujeto(['BioEYES,', a, nonprofit, outreach, program, using, zebrafish, to, excite, and, educate, 'K-12', students, about, science, and, how, to, think, and]), verbo([act]), complemento([like, 'scientists,', has, been, integrated, into, hundreds, of, 'under-resourced', schools, since, 2002])]). relacion([sujeto(['We']), verbo([have]), complemento([analyzed, 19, ',', 463, participating, 'students\'', 'pre-', and, 'post-tests', within, the, program, to, examine, their, learning, growth, and, attitude, changes, towards, science])]). relacion([sujeto(['We']), verbo([found]), complemento([that, at, all, grade, 'levels,', 'BioEYES', effectively, increased, 'students\'', content, knowledge, and, produced, favorable, shifts, in, 'students\'', attitudes, about, science])]). relacion([sujeto(['Having', served, over, 100, ',', 0, 'students,', we]), verbo([find]), complemento([that, our, method, for, providing, 'student-centered', experiences, and, developing, 'long-term', partnerships, with, teachers, is, essential, for, the, growth, and, sustainability, of, outreach, and, school, collaborations])]). relacion([sujeto(['Adopted', in, 2000, ',', 'United', 'Nations', 'Millennium', 'Development', 'Goal', 4, set, a]), verbo([target]), complemento([to, reduce, child, mortality, by, two, thirds, by, 2015, ',', with, measles, vaccination, coverage, as, one, of, the, progress, indicators])]). relacion([sujeto(['In', 2010, ',', the, 'World', 'Health', 'Assembly', '(', 'WHA)', set, three, milestones, for, measles, control, by, 2015, :, 1, ')']), verbo([increase]), complemento([routine, coverage, with, the, first, dose, of, 'measles-containing', vaccine, '(', 'MCV1)', for, children, aged, 1, year, to, '≥90%', nationally, and, '≥80%', in, every, 'district;', 2, ')', reduce, global, annual, measles, incidence, to, &, 'lt;5', cases, per, 1, million, 'population;', and, 3, ')', reduce, global, measles, mortality, by, 95, '%', from, the, 2000, estimate, '(', 1, ',', 2, ')'])]). relacion([sujeto(['Countries', in, all, six, 'WHO', regions]), verbo([have]), complemento([adopted, measles, elimination, goals])]). relacion([sujeto(['This']), verbo([report]), complemento([updates, a, previous, report, '(', 3, ')', and, describes, progress, toward, global, measles, control, milestones, and, regional, measles, elimination, goals, during, 2000, -, 2015])]). relacion([sujeto(['During', this, 'period,', annual]), verbo([reported]), complemento([measles, incidence, decreased, 75, '%', ',', from, 146, to, 36, cases, per, 1, million, 'persons,', and, annual, estimated, measles, deaths, decreased, 79, '%', ',', from, 651, ',', 600, to, 134, ',', 200])]). relacion([sujeto(['Countries', and, their, partners, need, to]), verbo([act]), complemento([urgently, to, secure, political, 'commitment,', raise, the, visibility, of, 'measles,', increase, vaccination, 'coverage,', strengthen, 'surveillance,', and, mitigate, the, threat, of, decreasing, resources, for, immunization, once, polio, eradication, is, achieved])]). relacion([sujeto(['We', sought, to, identify, factors]), verbo([associated]), complemento([with, condom, use, during, anal, intercourse, among, 'self-identified', human, immunodeficiency, 'virus-negative', 'gay,', 'bisexual,', and, other, men, who, have, sex, with, men, '(', 'GBM)', in, 'Vancouver,', 'Canada', following, &, 'quot;treatment', as, 'prevention"', '(', 'TasP)', 'scale-up', in, 2010])]). relacion([sujeto(['Sexually', active, 'GBM', were]), verbo([recruited]), complemento([using, 'respondent-driven', sampling, from, 2012, to, 2014])]). relacion([sujeto(['Accounting', for, clustering, at, the, 'respondent-driven', sampling, 'chain-level', and, 'participant-level,', factors]), verbo([associated]), complemento([with, 'event-level', condom, use, versus, nonuse, were, determined, using, a, multivariable, generalized, linear, mixed, model, built, using, backward, selection, and, 'AIC', minimization])]). relacion([sujeto(['Of', 513, 'participants,', 436, 'GBM', '(', 85, '%', ')']), verbo([reported]), complemento([a, total, of, 1196, anal, sex, events, with, 56, '%', condom, use])]). relacion([sujeto(['The', proportion, of, 'condom-protected', sexual, events]), verbo([decreased]), complemento([monthly, over, the, study, period, '(', odds, ratio, '[', 'OR],', 0.95, per, 'month,', 95, '%', confidence, interval, '[', 'CI],', 0.92, -, 0.98, ')'])]). relacion([sujeto(['The', 'TasP', practices, and, attitudes, were, significantly]), verbo([associated]), complemento([with, lower, odds, of, condom, use, at, the, univariate, 'level,', but, were, no, longer, significant, at, multivariate, level])]). relacion([sujeto(['In', the, multivariable, 'model,', 'event-level', partner, methamphetamine, use, '(', adjusted, 'OR', '[', 'aOR],', 0.18, ;, 95, '%', 'CI,', 0.06, -, 0.58, ')', ',', frequency, of, recent, anal, intercourse, with, that, partner, '(', 'aOR,', 0.97, per, 'act;', 95, '%', 'CI,', 0.95, -, 0.98, ')', and, time, since, first, sex, with, that, partner, '(', 'aOR,', 0.97, per, 6, 'months;', 95, '%', 'CI,', 0.95, -, 0.99, ')', were]), verbo([associated]), complemento([with, lower, odds, of, condom, 'use,', whereas, 'event-level', participant, alcohol, use, '(', 'aOR,', 1.41, ;, 95, '%', 'CI,', 1.01, -, 1.98, ')', and, no, planned, future, sex, with, that, partner, '(', 'aOR,', 1.56, ;, 95, '%', 'CI,', 1.08, -, 2.27, ')', were, associated, with, greater, odds, of, condom, use])]). relacion([sujeto(['Event-level', 'receptive-only', '(', 'aOR,', 2.1, ;, 95, '%', 'CI,', 1.38, -, 3.2, ')', or, 'insertive-only', '(', 'aOR,', 2.53, ;, 95, '%', 'CI,', 1.64, -, 3.9, ')', sexual, positions, were]), verbo([associated]), complemento([with, greater, odds, of, condom, use, compared, with, reporting, both, positions])]). relacion([sujeto(['Existing', implantable, stimulators, use, powering, approaches, that, result, in, stiff, and, bulky, systems, or, result, in, systems, incapable, of, producing, the, current, magnitudes]), verbo([required]), complemento([for, neuromuscular, stimulation])]). relacion([sujeto(['The', implants]), verbo([act]), complemento([as, rectifiers, of, 'HF', current, that, flows, through, the, tissues, by, galvanic, 'coupling,', transforming, this, current, into, low, frequency, current, capable, of, performing, neuromuscular, stimulation])]). relacion([sujeto(['Families', completed, 'Pediatric', 'Asthma', 'Caregiver\'s', 'Quality', of, 'Life', 'Questionnaire', '(', 'PACQLQ),', the, 'Asthma', 'Control', 'Test™', '(', 'ACT),', and]), verbo([reported]), complemento([the, number, of, 'days/month', of, albuterol, use, and, wheezing, at, each, clinic, visit])]). relacion([sujeto(['The', mean, total, 'PACQLQ', significantly]), verbo([increased]), complemento([over, the, 3, -, year, period, '(', 'F', =, 67.418, ',', 'p<'])]). relacion([sujeto(['PACQLQ', scores, were, significantly]), verbo([associated]), complemento([with, improved, 'ACT', scores, '(', r, =])]). relacion([sujeto(['Viewed', objects]), verbo([have]), complemento([been, shown, to, afford, suitable, 'actions,', even, in, the, absence, of, any, intention, to, act])]). relacion([sujeto(['Critically,', the, restriction, of, the, 'participants\'', action, possibility]), verbo([led]), complemento([to, a, significant, reduction, of, this, effect, and, significantly, improved, the, model, prediction, of, the, 'participants\'', gaze, behavior])]). relacion([sujeto(['Second,', postural, information]), verbo([interacts]), complemento([with, visual, information, to, the, generation, of, priority, maps, of, fixation, behavior])]). relacion([sujeto(['(', 'PsycINFO', 'Database', 'Record', 'Research', on, 'stimulus-response', '(', 'S-R)', associations, as, the, basis, of, behavioral, automaticity]), verbo([has]), complemento([a, long, history])]). relacion([sujeto(['Traditionally,', it, was, assumed, that, 'S-R', associations, are, formed, as, a, consequence, of, the, '(', 'repeated)', 'co-occurrence', of, stimulus, and, 'response,', that, 'is,', when, participants]), verbo([act]), complemento([upon, stimuli])]). relacion([sujeto(['In', an, 'item-specific', priming, 'paradigm,', participants, either, classified, everyday, objects, by, performing, a, left, or, right, key, press, '(', 'task-set', 'execution)', or, they, were, verbally, presented, with, information, regarding, an, 'object\'s', class, and]), verbo([associated]), complemento([action, while, they, passively, viewed, the, object, '(', verbal, 'coding)'])]). relacion([sujeto(['Both', 'S-R', associations, created, by, 'task-set', execution, and, by, verbal, coding]), verbo([led]), complemento([to, the, later, retrieval, of, both, the, 'stimulus-action', component, and, the, 'stimulus-classification', component, of, 'S-R', associations])]). relacion([sujeto(['The', automaticity, of, 'S-R', associations, formed, in, the, absence, of, action]), verbo([reveals]), complemento([the, striking, adaptability, of, human, action, control])]). relacion([sujeto(['However,', outside, the, domains, of, speech, and, 'music,', little, is, known, about, whether, humans, can]), verbo([recognize]), complemento([and, act, upon, the, intentions, of, another, 'agent\'s', actions, detected, through, auditory, information, alone])]). relacion([sujeto(['We']), verbo([suggest]), complemento([that, athletes, present, better, action, anticipation, by, being, able, to, pick, up, and, use, the, relevant, kinematic, features, of, deceptive, movement, from, 'event-related', sounds, alone])]). relacion([sujeto(['This', result]), verbo([suggests]), complemento([that, action, intention, can, be, perceived, through, the, sound, a, movement, makes, and, that, the, ability, to, determine, another, 'person\'s', action, intention, from, the, information, conveyed, through, sound, is, honed, through, practice])]). relacion([sujeto(['The', system, relies, on, a, postnuclear, supernatant, '(', 'PNS),', which, is, prepared, from, 'rat/mouse', 'liver,', to]), verbo([act]), complemento([as, a, source, of, peroxisomes, and, cytosolic, components])]). relacion([sujeto(['A', typical, in, vitro, assay, comprises, the, following, 'steps:', '(', 'i)', incubation, of, the, 'PNS', with, an, in, 'vitro-synthesized', '(', 35, ')', 'S-labeled', reporter, 'protein;', '(', 'ii)', treatment, of, the, organelle, suspension, with, a, protease, that, degrades, reporter, proteins, that]), verbo([have]), complemento([not, associated, with, 'peroxisomes;', and, '(', 'iii)', 'SDS-PAGE/autoradiography', analysis])]). relacion([sujeto(['To', study, transport, of, proteins, into, 'peroxisomes,', it, is, possible, to, use, 'organelle-resident', proteins, that, contain, a, peroxisomal]), verbo([targeting]), complemento([signal, '(', 'PTS)', as, reporters, in, the, assay])]). relacion([sujeto(['PEX7)', can, be, used, to]), verbo([report]), complemento([the, dynamics, of, shuttling, proteins, that, mediate, the, import, process])]). relacion([sujeto(['We', also, describe, strategies, to, fortify, the, system, with, recombinant, proteins, to]), verbo([increase]), complemento([import, yields, and, block, specific, parts, of, the, machinery, at, a, number, of, steps])]). relacion([sujeto(['The', present, study, investigates, whether, the, chronic, 'low-dose', radiation, exposure]), verbo([induces]), complemento([an, in, vivo, 'radio-adaptive', response, in, individuals, from, 'high-level', natural, radiation, areas, '(', 'HLNRA)', of, the, 'Kerala', coast])]). relacion([sujeto(['Thus,']), verbo([increased]), complemento([level, of, chronic, 'low-dose', radiation, '(', &, 'gt;5'])]). relacion([sujeto([0, 'mGy/year)', seems, to]), verbo([act]), complemento([as, a, priming, dose, resulting, in, the, induction, of, an, in, vivo, 'radio-adaptive', response, in, elder, individuals, of, the, 'Kerala', coast])]). relacion([sujeto(['AOX']), verbo([acts]), complemento([as, a, means, to, relax, the, highly, coupled, and, tensed, electron, transport, process, in, mitochondria, thus, providing, and, maintaining, the, much, needed, metabolic, homeostasis, by, directly, reducing, oxygen, to, water])]). relacion([sujeto(['In', the, process, 'AOX', also]), verbo([act]), complemento([as, facilitator, for, signalling, molecules, conveying, the, metabolic, status, of, mitochondria, to, the, nucleus, and, thus, able, to, influence, nuclear, gene, expression])]). relacion([sujeto(['AOX']), verbo([mediated]), complemento([signalling, and, metabolic, activities, are, very, much, important, for, plant, stress, response])]). relacion([sujeto(['The', review]), verbo([provides]), complemento([a, gist, of, regulation, and, functioning, of, 'AOX'])]). relacion([sujeto(['Here,', we, demonstrated, that, a, 'fucose-containing', fraction, of, 'Ling-Zhi', '(', 'FFLZ)', reduced, tumor, size, and]), verbo([suppressed]), complemento([metastasis, in, vivo])]). relacion([sujeto(['Furthermore,', 'FFLZ']), verbo([inhibited]), complemento([breast, cancer, cell, migration, and, altered, the, 'epithelial-to-mesenchymal', transition, '(', 'EMT)', phenotype])]). relacion([sujeto(['Transforming', growth, 'factor-β', receptor, '(', 'TGFR)', pathways]), verbo([act]), complemento([as, key, mediators, to, promote, tumor, progression, and, metastasis])]). relacion([sujeto(['We']), verbo([found]), complemento([that, 'FFLZ', 'down-regulated', 'TGFR', and, downstream, signaling, 'pathways,', including, the, phosphorylation, of, 'Smad2/3', and, the, expression, of, 'Smad4'])]). relacion([sujeto(['In', an, investigation, of, the, underlying, 'mechanisms,', we]), verbo([found]), complemento([that, 'FFLZ', enhanced, the, 'Smurf2-dependent', ubiquitination, of, 'TGFR', by, disrupting, the, balance, of, the, lipid, 'rafts,', promoted, the, &, 'quot;re-localization"', of, the, 'TGFR', to, the, 'caveolae,', and, facilitated, the, degradation, of, 'TGFR'])]). relacion([sujeto(['Together,', our, data, indicated, that, 'FFLZ', is]), verbo([associated]), complemento([with, the, inhibition, of, 'EMT', and, the, prevention, of, metastasis, by, promoting, 'ubiquitination-dependent', 'TGFR', degradation, and, abolishing, 'TGFR', signaling, pathways])]). relacion([sujeto(['Moreover,', the, combination, of, 'FFLZ', and, trastuzumab, synergistically]), verbo([inhibited]), complemento([the, viability, of, certain, 'trastuzumab-resistant', human, breast, cancer, cells])]). relacion([sujeto(['Especially', in, 'WSe2,', sharp, emission, features]), verbo([have]), complemento([been, observed, at, cryogenic, 'temperatures,', which, act, as, single, photon, sources])]). relacion([sujeto(['Tight', exciton, localization]), verbo([has]), complemento([been, assumed, to, induce, an, anharmonic, excitation, 'spectrum;', 'however,', the, evidence, of, the, 'hypothesis,', namely, the, demonstration, of, a, localized, 'biexciton,', is, elusive])]). relacion([sujeto(['Here', we, unambiguously, demonstrate, the, existence, of, a, localized, biexciton, in, a, monolayer, of, 'WSe2,', which]), verbo([triggers]), complemento([an, emission, cascade, of, single, photons])]). relacion([sujeto(['With', the, emergence, on, the, clandestine, market, in, the, last, few, years, of, a, large, number, of, new, cathinone, 'analogs,', termed, &, 'quot;synthetic', 'cathinones",', and, the, realization, that, they, likely]), verbo([act]), complemento([at, 'dopamine,', 'norepinephrine,', 'and/or', serotonin, transporters, as, releasing, agents, '(', i])]). relacion([sujeto([',', as, transport, 'blockers),', it]), verbo([has]), complemento([now, become, possible, to, better, examine, their, 'SAR', and, even, their, quantitative, 'SAR', '(', 'QSAR),', in, a, more, effective, and, systematic, manner])]). relacion([sujeto(['An', 'SAR', picture, is, beginning, to, 'emerge,', and, key, structural, 'features,', such, as, the, nature, of, the, terminal, 'amine,', the, size, of, the, 'α-substituent,', 'stereochemistry,', and, the, presence, and, position, of, aromatic, 'substituents,', are, being]), verbo([found]), complemento([to, impact, action, '(', i])]). relacion([sujeto([',', as]), verbo([releasing]), complemento([agents, or, reuptake, 'inhibitors)', and, transporter, selectivity])]). relacion([sujeto(['Although', demands, for, human, hepatocytes, are]), verbo([increasing]), complemento([in, not, only, cell, therapy, but, also, drug, 'development,', it, is, highly, difficult, to, obtain, good, lots, of, hepatocytes, from, human, liver, tissue])]). relacion([sujeto(['All', procedures, described, here, are, compliant, with, good, manufacturing, procedure, '(', 'GMP)', in, cell, processing, 'facility,', approved, by, the]), verbo([act]), complemento([on, measures, to, ensure, safety, of, regenerative, medicine, and, ethical, regulations, in, 'Japan'])]). relacion([sujeto(['The', extrinsic, muscles, are, subdivided, into, small, groups, of, fibers, depending, on, their, spatial, 'interrelationships,']), verbo([suggesting]), complemento([that, they, contain, many, functional, units])]). relacion([sujeto(['Some', units]), verbo([act]), complemento(['separately,', and, others, cooperate, across, the, traditional, boundaries, of, the, muscles])]). relacion([sujeto(['To', summarize, recent, research, on, unintended, consequences]), verbo([associated]), complemento([with, implementation, and, use, of, health, information, technology, '(', health, 'IT)'])]). relacion([sujeto(['Included', in, the, review, are, original, empirical, investigations, published, in, 'English', between, 2014, and, 2015, that]), verbo([reported]), complemento([unintended, effects, introduced, by, adoption, of, digital, interventions])]). relacion([sujeto(['Our', analysis, focuses, on, the, trends, of, this, steam, of, 'research,', areas, in, which, unintended, consequences]), verbo([have]), complemento([continued, to, be, 'reported,', and, common, themes, that, emerge, from, the, findings, of, these, studies])]). relacion([sujeto(['However,', more, 'mixed-methods', studies, are, needed, to, develop, deeper, insights, into, the, observed, unintended, adverse, 'outcomes,', including, their, root]), verbo([causes]), complemento([and, remedies])]). relacion([sujeto(['We', also, encourage, future, research, to, go, beyond, the, paradigm, of, simply, describing, unintended, 'consequences,', and, to, develop, and, test, solutions, that, can]), verbo([prevent]), complemento([or, minimize, their, impact])]). relacion([sujeto(['If']), verbo([increased]), complemento([to, levels, which, cannot, be, neutralized, by, the, defense, 'mechanisms,', they, damage, biological, 'molecules,', alter, their, 'functions,', and, also, act, as, signaling, molecules, thus, generating, a, spectrum, of, pathologies])]). relacion([sujeto(['In', this, 'review,', we, summarize, current, data, on, oxidative, stress, markers]), verbo([associated]), complemento([with, human, immunodeficiency, virus, 'type-1', '(', 'HIV-1)', 'infection,', analyze, mechanisms, by, which, this, virus, triggers, massive, 'ROS', 'production,', and, describe, the, status, of, various, defense, mechanisms, of, the, infected, host, cell])]). relacion([sujeto(['In', 'addition,', we]), verbo([have]), complemento([scrutinized, scarce, data, on, the, effect, of, 'ROS', on, 'HIV-1', replication])]). relacion([sujeto(['Finally,', we, present, current, state, of, knowledge, on, the, redox, alterations, as, crucial, factors, of, 'HIV-1', 'pathogenicity,', such, as, neurotoxicity, and, 'dementia,', exhaustion, of, 'CD4(+)/CD8(+)', 'T-cells,', predisposition, to, lung, 'infections,', and, certain, side, effects, of, the, antiretroviral, 'therapy,', and, compare, them, to, the, pathologies]), verbo([associated]), complemento([with, the, nitrosative, stress])]). relacion([sujeto(['IL-22', was]), verbo([found]), complemento([to, be, elevated, in, all, three, conditions])]). relacion([sujeto(['Elevated', serum, 'IL-22', was, independently]), verbo([associated]), complemento([with, the, incidence, of, 'T2DM', and, 'CAD'])]). relacion([sujeto(['Conversely,', 'IL-22', was]), verbo([found]), complemento([to, protect, endothelial, cells, from, 'glucose-', and, 'lysophosphatidylcholine-', '(', 'LPC-)', induced, 'injury,', and, 'IL-22R1', expression, on, endothelial, cells, was, increased, upon, treatment, with, high, glucose, and, 'LPC'])]). relacion([sujeto(['Our', results]), verbo([suggest]), complemento([that, 'IL-22', functions, as, a, 'double-edged', sword, in, 'T2DM', and, 'CAD', and, that, 'IL-22', may, be, used, in, the, treatment, of, chronic, inflammatory, diseases, such, as, 'T2DM', and, 'CAD'])]). relacion([sujeto(['Genetic', polymorphisms, in, the, endoplasmic, reticulum, aminopeptidase, '(', 'ERAP)1', and, 'ERAP2', genes]), verbo([have]), complemento([been, associated, with, several, autoimmune, diseases, '(', 'AIDs)', at, a, 'genome-wide', significance, level])]). relacion([sujeto(['Our', study, therefore]), verbo([reveals]), complemento([the, 'fine-mapped', 'AID', risk, variants, that, act, as, eQTLs, with, 'ERAP2', in, 'thymus,', and, highlights, the, potential, causal, regulatory, variants])]). relacion([sujeto(['Fasting', hypertriglyceridemia, is, positively]), verbo([associated]), complemento([with, the, morbidity, of, coronary, heart, disease, '(', 'CHD),', and, postprandial, '(', 'non-fasting)', hypertriglyceridemia, is, also, correlated, with, the, risk, status, for, 'CHD,', which, is, related, to, the, increase, in, chylomicron, '(', 'CM)', remnant, lipoproteins, produced, from, the, intestine])]). relacion([sujeto(['CM', remnant, 'particles,', as, well, as, oxidized, low, density, lipoprotein, '(', 'LDL)', or, very, low, density, lipoprotein, '(', 'VLDL)', 'remnants,', are, highly, atherogenic, and]), verbo([act]), complemento([by, enhancing, systemic, 'inflammation,', platelet, 'activation,', 'coagulation,', thrombus, 'formation,', and, macrophage, foam, cell, formation])]). relacion([sujeto(['We']), verbo([have]), complemento([developed, an, assay, of, apolipoprotein, '(', 'apo)B-48', levels, to, evaluate, the, accumulation, of, 'CM', remnants])]). relacion([sujeto(['Since', the, accumulation, of, 'CM', remnants, correlates, to, impaired, lipid, and, glucose, metabolism, and, atherosclerotic, cardiovascular, 'events,', further, studies, are]), verbo([required]), complemento([to, investigate, the, 'characteristics,', physiological, 'activities,', and, functions, of, 'CM', remnants, for, the, development, of, new, interventions, to, reduce, atherogenicity])]). relacion([sujeto(['Epidemiological', and, experimental, data]), verbo([have]), complemento([indicated, the, beneficial, and, adverse, effects, of, estrogenic, replacement, therapy])]). relacion([sujeto(['In', the, present, 'study,', we, explored, the, effect, of, ethinylestradiol, '(', 'EE)', and, 17, 'β-estradiol', '(', 'E2)', on, screening, 'tests,', prothrombin, time, '(', 'PT)', and]), verbo([activated]), complemento([partial, thromboplastin, time, '(', 'APTT),', as, well, as, the, activity, of, coagulation, factors, '(', 'FVII,', 'FX,', 'FXI,', and, 'FXII)', in, male, 'Wistar', rats])]). relacion([sujeto(['Our', findings]), verbo([suggest]), complemento([that, 'EE', and, 'E2', produce, different, effects, on, coagulation, and, that, 'EE', seems, to, act, across, an, inhibitory, mechanism, of, coagulation, factor, activity, in, the, present, experimental, model])]). relacion([sujeto(['MicroRNAs', '(', 'miRNAs)', are, small, 'non-coding', 'RNAs', that]), verbo([act]), complemento([as, 'post-transcriptional', gene, regulators])]). relacion([sujeto(['They', are]), verbo([involved]), complemento([in, the, pathogenesis, of, different, disorders, including, heart, diseases])]). relacion([sujeto(['Together', with, alterations, in, the, various, potential, signaling, 'pathways,', modification, in, miRNA, expression]), verbo([has]), complemento([been, suggested, as, a, part, of, the, response, network, following, 'ischemia/reperfusion', '(', 'I/R)'])]). relacion([sujeto(['In', 'addition,', cardiac, mitochondrial, homeostasis, is, closely]), verbo([associated]), complemento([with, cardiac, function, and, impairment, of, mitochondrial, activity, occurred, after, 'ischemia/reperfusion', injury])]). relacion([sujeto(['Accumulating', evidence]), verbo([has]), complemento([indicated, that, aberrantly, expressed, microRNAs, '(', 'miRs)', are, extensively, involved, in, cancer, development, and, progression])]). relacion([sujeto(['MiR-639']), verbo([has]), complemento([been, reported, to, act, as, tumor, promoter, in, various, types, of, cancer])]). relacion([sujeto(['However,', the, biological, function, and, underlying, molecular, mechanism, of, 'miR-639', in, thyroid, carcinoma, '(', 'TC)']), verbo([have]), complemento([not, been, intensively, investigated])]). relacion([sujeto(['We']), verbo([found]), complemento([that, 'miR-639', expression, was, upregulated, in, 'TC', cells, and, clinical, tissues])]). relacion([sujeto(['Overexpression', of, 'miR-639']), verbo([promoted]), complemento(['TC', cell, proliferation, and, cell, 'cycle,', with, increased, expression, of, 'CyclinE', and, 'c-myc,', whereas, 'miR-639-in', reverses, the, function])]). relacion([sujeto(['Using', prediction, software, and, luciferase, reporter, 'assay,', we]), verbo([found]), complemento([that, 'CDKN1A', was, a, target, of, 'miR-639'])]). relacion([sujeto(['In', 'summary,', our, data, demonstrated, that, 'miR-639', upregulation, was]), verbo([associated]), complemento([with, development, of, 'TC,', 'miR-639', promoted, cell, proliferation, and, cell, cycle, by, targeting, 'CDKN1A', in, 'TC'])]). relacion([sujeto(['According', to, the, 'US', 'Affordable', 'Care', 'Act,', restaurant, chains, are]), verbo([required]), complemento([to, provide, energy, '(', 'calorie)', and, other, nutrition, information, on, their, menu])]). relacion([sujeto(['Photoprotection', and, antioxidant, related, 'genes,', as, well, as, genes]), verbo([involved]), complemento([in, sexual, reproduction, were, analyzed])]). relacion([sujeto([rhodozyma, strains, and, other, 'Cystofilobasidiales']), verbo([have]), complemento([the, highest, number, of, 'intron-containing', genes, and, highest, number, of, introns, per, gene])]). relacion([sujeto(['A', hitherto, unknown, gene, cluster, potentially, responsible, for, photoprotection, '(', 'mycosporines)', was]), verbo([found]), complemento([in, the, newly, sequenced, 'P'])]). relacion([sujeto(['A', broad, battery, of, enzymes, that]), verbo([act]), complemento([as, scavengers, of, free, radical, oxygen, species, were, 'detected,', including, catalases, and, superoxide, dismutases, '(', 'SODs)'])]). relacion([sujeto(['Additionally,', genes]), verbo([involved]), complemento([in, sexual, reproduction, were, found, and, annotated])]). relacion([sujeto([rhodozyma, is, now, 'available,', and, comparison, with, that, of, the, 'Patagonian', population]), verbo([suggests]), complemento([the, latter, deserves, to, be, assigned, to, a, distinct, variety])]). relacion([sujeto([rhodozyma, is, one, of, the, fungi, most, 'well-equipped', to, cope, with, environmental, oxidative, 'stress,', a, factor, that]), verbo([has]), complemento([probably, contributed, to, shaping, its, genome])]). relacion([sujeto(['A', basic, task, in, drug, discovery, is, to]), verbo([find]), complemento([new, medication, in, the, form, of, candidate, compounds, that, act, on, a, target, protein])]). relacion([sujeto(['In', other, 'words,', a, drug]), verbo([has]), complemento([to, interact, with, a, target, and, such, 'drug-target', interaction, '(', 'DTI)', is, not, expected, to, be, random])]). relacion([sujeto(['Currently,', a, number, of, computational, methods]), verbo([have]), complemento([been, proposed, to, predict, 'DTIs', based, on, their, similarity])]). relacion([sujeto(['As', a, 'result,', some, methods]), verbo([have]), complemento([been, proposed, to, try, to, discover, patterns, in, physicochemical, interactions])]). relacion([sujeto(['In', this, 'paper,', we, present, a, novel, 'approach,', called, 'ODT', '(', one, class, drug]), verbo([target]), complemento([interaction, 'prediction),', for, such, purpose])]). relacion([sujeto(['One', main, task, of, 'ODT', is, to, discover, association, patterns, between]), verbo([interacting]), complemento([drugs, and, proteins, from, the, chemical, structure, of, the, former, and, the, protein, sequence, network, of, the, latter])]). relacion([sujeto(['The', 'C/EBPɛ', is]), verbo([involved]), complemento([in, terminal, differentiation, and, functional, maturity, of, granulocyte, progenitor, cells, and, in, cell, apoptosis, during, myeloid, differentiation])]). relacion([sujeto(['A', 'C/EBPE', gene]), verbo([has]), complemento([recently, been, described, as, a, candidate, gene, involved, in, clinical, variability, of, 'β-thalassemia', '(', 'β-thal)'])]). relacion([sujeto(['Thus,', the, 'T', allele, is, consequently]), verbo([associated]), complemento([with, the, 'β-TI', group, '(', p, =, 10, '(', -, 3, ')', ')'])]). relacion([sujeto(['According', to, the, 'Human', 'Splicing', 'Finder', '(', version, 3.0, ',', 'Marseille,', 'France),', the, presence, of, the, rs45496295, polymorphism]), verbo([leads]), complemento([the, creation, of, a, new, intronic, exotic, splicing, enhancer, '(', 'ESE)', site])]). relacion([sujeto(['Moreover,', the, 'T', allele, of, rs45496295, is]), verbo([associated]), complemento([with, a, lower, transfusion, regimen, '(', p, =, 10, '(', -, 3, ')', ')', and, a, higher, pretransfusion, hemoglobin, '(', 'Hb)', rate, '(', p, =])]). relacion([sujeto(['The', comparison, of, several, factors, concerning, 'T', allele, carriers, and, 'non-carriers', showed, that, the, 'T', allele, does, not]), verbo([act]), complemento([on, the, 'Hb', 'F', rate])]). relacion([sujeto(['The', 'T', allele, of, 'rs45496295,']), verbo([associated]), complemento([with, moderate, type, of, 'β-thal,', seems, to, modify, the, 'C/EBPɛ', 'action,', thereby, preventing, the, hemolysis])]). relacion([sujeto(['Here,', we]), verbo([find]), complemento([that, ablation, of, glycosaminoglycan, '(', 'GAG)', side, chains, of, proteoglycans, in, the, neuroretina, disrupts, the, retinal, basement, 'membrane,', leading, to, arrested, astrocyte, migration, and, reduced, angiogenesis])]). relacion([sujeto(['Using', genetic, deletion, and, 'time-lapse', 'imaging,', we, show, that, retinal, astrocytes]), verbo([require]), complemento(['neuronal-derived', 'PDGF', as, a, chemoattractive, cue, and, the, retinal, basement, membrane, as, a, migratory, substrate])]). relacion([sujeto(['In', 'contrast,', enzymatic, removal, of, heparan, sulfates, and, chondroitin, sulfates, together]), verbo([inhibits]), complemento([de, novo, laminin, network, assembly])]). relacion([sujeto(['These', results, indicate, that, both, heparan, and, chondroitin, sulfate, proteoglycans]), verbo([participate]), complemento([in, retinal, 'basement membrane', 'assembly,', thus, promoting, astrocyte, migration, and, angiogenesis])]). relacion([sujeto(['Hypothalamic', oxytocin, '(', 'OXT)', and, arginine, vasopressin, '(', 'AVP)', are, known, to]), verbo([act]), complemento([oppositely, on, 'hypothalamic-pituitary-adrenal', '(', 'HPA)', 'axis,', stress, response, and, gastrointestinal, '(', 'GI)', motility])]). relacion([sujeto(['Using', 'in-vivo', brain, microdialysis, in, 'rats,', the, changes, 'OXT', and, 'AVP']), verbo([release]), complemento([from, hypothalamus, were, monitored, under, basal, 'non-stressed', '(', 'NS)', conditions, and, in, rats, exposed, to, acute, stress, '(', 'AS),', 'CHS', and, 'CHeS'])]). relacion([sujeto(['OXT', was, measured, higher, in, 'AS', and, 'CHS', 'group,', but, not, in, 'CHeS-loaded', 'rats,', whereas, 'AVP', significantly]), verbo([increased]), complemento([in, rats, exposed, to, 'AS', and, 'CHeS'])]). relacion([sujeto(['The', 'CHS-induced', restoration, was]), verbo([prevented]), complemento([by, 'L-371257,', whereas, 'SSR-149415', abolished, the, 'CHeS-induced', impaired, 'GE'])]). relacion([sujeto(['Under', long, term, stressed, 'conditions,', the]), verbo([release]), complemento([of, 'AVP', and, 'OXT', from, hypothalamus, may, vary, depending, on, the, content, of, the, stressors])]). relacion([sujeto(['Central', 'AVP', appears, to]), verbo([act]), complemento([oppositely, to, 'OXT', by, mediating, 'CHeS-induced', gastric, motor, maladaptation])]). relacion([sujeto(['Regulators', of, 'G', protein, signaling, '(', 'RGS)', proteins]), verbo([act]), complemento([as, 'GTPase', activating, proteins, to, negatively, regulate, 'G', 'protein-coupled', receptor, '(', 'GPCR)', signaling])]). relacion([sujeto(['Although', several, 'RGS', proteins, including, 'RGS2,', 'RGS16,', 'RGS10,', and, 'RGS18', are]), verbo([expressed]), complemento([in, human, and, mouse, 'platelets,', the, respective, unique, 'function(s)', of, each, have, not, been, fully, delineated])]). relacion([sujeto(['RGS10', is, a, member, of, the, 'D/R12', subfamily, of, 'RGS', proteins, and, is]), verbo([expressed]), complemento([in, 'microglia,', 'macrophages,', 'megakaryocytes,', and, platelets])]). relacion([sujeto(['These', findings]), verbo([suggest]), complemento([a, 'unique,', 'non-redundant', role, of, 'RGS10', in, modulating, the, hemostatic, and, thrombotic, functions, of, platelets, in, mice])]). relacion([sujeto(['RGS10', thus, represents, a, potential, therapeutic]), verbo([target]), complemento([to, control, platelet, activity, 'and/or', hypercoagulable, states])]). relacion([sujeto(['Our', new, simulations, indicate, that, the, pinned, regions, which, 'form,', presumably, due, to, 'Ca2+', ions, serving, as, bridging, agent, between, the, distal, and, the, proximal, 'bilayer,']), verbo([act]), complemento([as, nucleation, sites, for, the, ruptures])]). relacion([sujeto(['Moreover,', assuming, that, the, pinning, sites]), verbo([cause]), complemento([a, 'non-zero', shear, 'modulus,', our, simulations, also, show, that, they, change, the, rupture, mode, from, floral, to, fractal])]). relacion([sujeto(['With']), verbo([increasing]), complemento([shear, modulus, the, pore, edges, start, to, 'branch,', favoring, fractal, morphologies])]). relacion([sujeto(['Climate', models, show, an, ongoing, poleward, expansion, and, intensification, of, the, global, wind, 'systems,', most, robustly, in, the, 'Southern', 'Hemisphere,', and, linear, dynamical, theory]), verbo([suggests]), complemento([that, western, boundary, currents, will, intensify, and, shift, poleward, as, a, result])]). relacion([sujeto(['Here', we, show, 'that,', despite, these, 'expectations,', the, 'Agulhas', 'Current']), verbo([has]), complemento([not, intensified, since, the, early, 1990, s])]). relacion([sujeto(['Instead,', we]), verbo([find]), complemento([that, it, has, broadened, as, a, result, of, more, eddy, activity])]). relacion([sujeto(['These', results, indicate, that, intensifying, winds, may, be]), verbo([increasing]), complemento([the, eddy, kinetic, energy, of, boundary, 'currents,', rather, than, their, mean, flow])]). relacion([sujeto(['This', could]), verbo([act]), complemento([to, decrease, poleward, heat, transport, and, increase, 'cross-frontal', exchange, of, nutrients, and, pollutants, between, the, coastal, ocean, and, the, deep, ocean])]). relacion([sujeto(['Medicine']), verbo([has]), complemento([traditionally, excluded, the, provision, of, deadly, medication, from, proper, practice])]). relacion([sujeto(['The', 'disease-metabolite-pathway', associations, pointed, out, the, importance, of, membrane, transport, '(', through, 'ATP']), verbo([binding]), complemento([cassette, 'transporters),', particularly, of, arginine, and, proline, amino, acids, in, all, three, neurodegenerative, diseases])]). relacion([sujeto(['When', 'disease-specific', and, common, metabolic, pathways, were, queried, by, using, the, pathway, enrichment, 'analyses,', we]), verbo([found]), complemento([that, 'alanine,', 'aspartate,', 'glutamate,', and, purine, metabolism, might, act, as, alternative, pathways, to, overcome, inadequate, glucose, supply, and, energy, crisis, in, neurodegeneration])]). relacion([sujeto(['Future', research, investments, in, metabolomics, of, complex, diseases, might]), verbo([provide]), complemento([new, insights, on, 'AD,', 'PD,', and, 'ALS', that, continue, to, place, a, significant, burden, on, global, health])]). relacion([sujeto(['The', synthetic, surfactant, 'CHF5633']), verbo([has]), complemento([proven, biophysical, effectiveness, 'and,', 'moreover,', demonstrated, 'anti-inflammatory', effects, in, 'LPS-stimulated', monocytes])]). relacion([sujeto(['CHF5633', did, not]), verbo([induce]), complemento(['pro-inflammation,', and, did, not, aggravate, 'Ureaplasma-induced', 'pro-inflammatory', cytokine, responses])]). relacion([sujeto(['It']), verbo([suppressed]), complemento(['U'])]). relacion([sujeto([5, ')', in, neonatal, monocytes, and]), verbo([inhibited]), complemento(['Ureaplasma-induced', 'TNF-α', mRNA, '(', 'p < 0'])]). relacion([sujeto(['CHF5633', does, neither]), verbo([act]), complemento(['pro-apoptotic', nor, 'pro-inflammatory', in, native, and, 'Ureaplasma-infected', monocytes])]). relacion([sujeto(['Numerous', 'investigations,', and, especially, in, vitro, 'studies,', indicate, that, 'TGF-β1', may]), verbo([act]), complemento([as, an, important, regulator, of, bone, remodelling])]). relacion([sujeto(['Thus,', it, could, be, expected, that, disturbances, of, this, cytokine, production, observed, by, several, researchers, might, play, a, role, in, the, mechanism]), verbo([leading]), complemento([to, the, development, of, osteoporosis, in, girls, with, anorexia, nervosa, '(', 'AN)'])]). relacion([sujeto(['The', 'Cole', index, and, 'BMI', were, identified, to, be, significant, and, independent, predictors, of, 'CTx', '(', 'C,', 'AN,', and, 'C+AN', 'groups)', and, 'OPG', '(', 'AN', 'group);', the, 'Cole', 'index,', 'BMI,', and, 'TGF-β1', independently, predicted, the, 'OPG/sRANKL', ratio, '(', 'C,', 'AN,', and, 'C', +, 'AN', 'groups);', 'TGF-β1', was]), verbo([found]), complemento([to, be, an, independent, predictor, of, 'OC', '(', 'C', +, 'AN', 'group)'])]). relacion([sujeto(['Changes', in, bone, 'markers,', 'OPG,', 'and/or', 'OPG/sRANKL', ratio, observed, in, girls, with, 'AN', are]), verbo([associated]), complemento([with, changes, in, serum, 'TGF-β1', concentrations])]). relacion([sujeto(['TGF-β1', suppression, in, girls, with, 'AN', might]), verbo([lead]), complemento([to, disturbances, in, the, relationship, between, bone, metabolism, and, the, 'OPG/sRANKL', 'system,', 'which,', in, 'turn,', might, compromise, the, mechanism, compensating, for, bone, remodelling, disturbances])]). relacion([sujeto(['We', present, a, 'near-infrared', '(', 'NIR)', spectrum, measurement, method, using, a, 'Schottky', photodetector]), verbo([enhanced]), complemento([by, surface, plasmon, resonance, '(', 'SPR)'])]). relacion([sujeto(['An', 'Au', grating, was, fabricated, on, an, 'n-type', silicon, wafer, to, form, a, 'Schottky', barrier, and]), verbo([act]), complemento([as, an, 'SPR', coupler])]). relacion([sujeto(['The', resulting, photodetector]), verbo([provides]), complemento(['wavelength-selective', photodetection, depending, on, the, 'SPR', coupling, angle])]). relacion([sujeto(['In', this, 'letter,', we]), verbo([report]), complemento([on, quantum, light, emission, from, bulk, 'AlInAs', grown, on, 'InP(111)', substrates])]). relacion([sujeto(['We', demonstrate, the, capability, of, this, new, material, system, to]), verbo([act]), complemento([as, an, emitter, of, pure, single, photons, as, we, extract, 'g<sup>(2)</sup>-values', as, low, as, 'gcw(2)(0)=0'])]). relacion([sujeto(['We', use, an, approach, in, which, one, lens, controls, the, spot, 'divergence,', and, one, to, two, decentered, lenses]), verbo([act]), complemento([as, prisms, and, steer, the, beam])]). relacion([sujeto(['The', beam, scanning, angle, was, further]), verbo([enhanced]), complemento([to, '±75°', using, a, fisheye, lens])]). relacion([sujeto(['Reactive', oxygen, species, '(', 'ROS)', and, electric, currents]), verbo([modulate]), complemento(['regeneration;', 'however,', the, interplays, between, biochemical, and, biophysical, signals, during, regeneration, remain, poorly, understood])]). relacion([sujeto(['We', show, that, inhibition, of, 'NADPH', 'oxidases-mediated', production, of, 'ROS,', or, scavenging, or, blocking, their, diffusion, into, 'cells,', impairs, regeneration, and, consistently]), verbo([regulate]), complemento([the, dynamics, of, membrane, 'potential,', transepithelial, potential, '(', 'TEP)', and, electric, current, densities, '(', 'JI)', during, regeneration])]). relacion([sujeto(['Short-term', application, of, hydrogen, peroxide, '(', 'H2O2)', rescues, '(', from, depleted, 'ROS)', and]), verbo([gains]), complemento(['(', from, refractory, 'period)', 'regeneration,', 'TEP', increase, and, 'JI', reversal])]). relacion([sujeto(['H2O2', is, thereby, necessary, for, and, sufficient, to]), verbo([induce]), complemento([regeneration, and, to, regulate, 'TEP', and, 'JI', 'Epistasis', assays, show, that, 'voltage-gated', 'Na(+)', channels, act, downstream, of, 'H2O2', to, modulate, regeneration])]). relacion([sujeto(['Altogether,', these, results]), verbo([suggest]), complemento([a, novel, mechanism, for, regeneration, via, 'redox-bioelectric', orchestration])]). relacion([sujeto(['The', obstacles, to, the, development, of, therapeutic, aptamers, for, systemic, inflammatory, 'diseases,', such, as, nuclease, degradation, and, renal, 'clearance,']), verbo([have]), complemento([not, been, fully, overcome])]). relacion([sujeto(['Here,', we]), verbo([report]), complemento([a, novel, 'PEGylation', 'method,', 'sbC-PEGylation,', which, improves, the, pharmacokinetic, properties, of, 'RNA', aptamers, that, act, against, 'interleukin-17A', '(', 'IL-17A)', in, mice, and, monkeys])]). relacion([sujeto(['In', 'addition,', one, of, the, 'sbC-PEGylated', 'aptamers,', 17, 'M-382,']), verbo([inhibited]), complemento([the, 'interleukin-6', '(', 'IL-6)', production, induced, by, 'IL-17A', in, 'NIH3T3', cells, in, a, 'concentration-dependent', 'manner,', and, the, 'half-maximal', inhibitory, concentration, of, 'sbC-PEGylated', 17, 'M-382', was, two, times, lower, than, that, of, 'non-PEGylated', 17, 'M-382'])]). relacion([sujeto(['Furthermore,', the, intraperitoneal, administration, of, 'sbC-PEGylated', 17, 'M-382', significantly]), verbo([inhibited]), complemento([the, 'IL-6', production, induced, by, 'IL-17A', in, a, mouse, air, pouch, model])]). relacion([sujeto(['Our', findings]), verbo([suggest]), complemento([that, the, novel, 'PEGylation', method, described, in, this, 'study,', 'sbC-PEGylation,', could, be, used, to, develop, 'anti-IL-17A', aptamers, as, a, therapeutic, option, for, systemic, inflammatory, disease])]). relacion([sujeto(['LncRNA', 'GAS5', was, identified, to, be]), verbo([involved]), complemento([in, tumorigenesis, of, several, cancers])]). relacion([sujeto(['We', showed, that, 'GAS5', expression, was]), verbo([decreased]), complemento([in, 'GC', tissue, and, inversed, correlated, with, 'up-regulated', expression, of, 'miR-23a'])]). relacion([sujeto(['GAS5', negatively]), verbo([regulated]), complemento(['miR-23a', expression, in, 'GC', cells])]). relacion([sujeto(['The', 'bio-informatics', prediction, showed, putative, 'miR-23a']), verbo([binding]), complemento([sites, within, 'GAS5', transcripts])]). relacion([sujeto(['Furthermore,', our, data, indicated, the, positive, regulation, of, 'GAS5', on, the, 'miR-23a', 'target,', 'MT2A,', wherein, 'GAS5']), verbo([suppressed]), complemento([the, negative, regulation, of, 'miR-23a', on, 'MT2A', by, binding, its, 3, '\'', 'UTR'])]). relacion([sujeto(['Additionally,', the, expression, of, 'MT2A', was, also]), verbo([decreased]), complemento([in, 'GC', 'tissues,', showing, a, positive, or, negative, correlation, with, 'GAS5', or, 'miR-23a,', respectively])]). relacion([sujeto(['These', observations]), verbo([suggested]), complemento([that, 'GAS5', could, act, as, a, ceRNA, play, critical, roles, in, 'GC', pathogenesis, and, might, serve, as, a, potential, therapeutic, target, for, the, treatment, of, gastric, cancer])]). relacion([sujeto(['MiR-143', as, a, tumor, 'suppressor,', is]), verbo([decreased]), complemento([in, malignant, 'tumors,', including, colorectal, cancer, '(', 'CRC)'])]). relacion([sujeto(['Target', prediction, programs, and, luciferase, reporter, assay, was, used, to, predict, the]), verbo([targets]), complemento([of, 'miR-143'])]). relacion([sujeto(['Following', overexpression, of, 'miR-143', in, 'CRC', 'cells,']), verbo([target]), complemento([gene, matrix, metallopeptidase, 7, '(', 'MMP7)', expression, was, detected, by, quantitative, 'real-time', 'PCR', '(', 'qRT-PCR)', and, western, blot])]). relacion([sujeto(['In', the, present, 'study,', 'Targetscan', predicted, that, 'miR-143', could, directly]), verbo([bind]), complemento([to, 3, '\'', -, 'UTR', of, 'MMP7', 'mRNA,', and, luciferase, reporter, assay, further, supportedthat, 'MMP7', might, act, as, a, direct, target, gene, of, 'miR-143'])]). relacion([sujeto(['Our', data, showed, that]), verbo([increased]), complemento([expression, of, 'miR-143', repressed, 'MMP7', expression, in, 'CRC', cells, both, in, mRNA, and, protein, levels])]). relacion([sujeto(['Furthermore,', 'qRT-PCR', showed, that, the, expression, of, 'MMP7', was]), verbo([increased]), complemento([in, 'CRC', tissues, and, cell, 'lines,', and, inversely, correlated, with, 'miR-143', expression, in, 'CRC', tissues])]). relacion([sujeto(['Finally,', our, results, indicated, that]), verbo([increased]), complemento([expression, of, 'MMP7', reversed, the, potential, influence, of, 'miR-143', on, 'CRC', cell, proliferation, and, invasion, ability])]). relacion([sujeto(['Our', results, indicated, that, 'miR-143', might]), verbo([act]), complemento([as, a, tumor, suppressor, by, targeting, 'MMP7', during, the, development, of, 'CRC'])]). relacion([sujeto(['A', tunable, resistive, pulse, 'sensor,', utilising, a, polyurethane, 'nanopore,']), verbo([has]), complemento([been, used, to, characterise, nanoparticles, as, they, traverse, the, pore, opening])]). relacion([sujeto(['Herein', we, demonstrate, that, the, translocation, 'speed,', conductive, and, resistive, pulse, 'magnitude,', can, be, used, to, infer, the, surface, charge, of, a, 'nanoparticle,', and]), verbo([act]), complemento([as, a, specific, transduction, signal, for, the, binding, of, metal, ions, to, ligands, on, the, particle, surface])]). relacion([sujeto(['Biphasic', pulses, are, becoming, a, powerful, means, to, characterise, 'materials,', and]), verbo([provide]), complemento([insight, into, the, translocation, 'mechanism,', and, herein, we, present, their, first, use, to, detect, the, presence, of, metal, ions, in, solution])]). relacion([sujeto(['The', method]), verbo([has]), complemento([potential, for, monitoring, heavy, metals, in, biological, and, environmental, samples])]). relacion([sujeto(['Proteins']), verbo([involved]), complemento([in, genetic, stability, maintenance, and, safeguarding, 'DNA', replication, act, not, only, against, cancer, initiation, but, could, also, play, a, major, role, in, sustaining, cancer, progression])]). relacion([sujeto(['Here,', we]), verbo([report]), complemento([that, the, 'FANC', pathway, is, highly, expressed, in, metastatic, melanoma, harboring, the, oncogenic, 'microphthalmia-associated', transcription, factor, '(', 'MiTF)'])]). relacion([sujeto(['We', demonstrate, that, the, 'FANC', pathway]), verbo([acts]), complemento([downstream, 'MiTF', and, establish, the, existence, of, an, epistatic, relationship, between, 'MiTF', and, the, 'FANC', pathway])]). relacion([sujeto(['Our', findings, point, to, a, central, role, of, the, 'FANC', pathway, in, cellular, and, chromosomal, resistance, to, both, 'DNA', damage, and]), verbo([targeted]), complemento([therapies, in, melanoma, cells])]). relacion([sujeto(['Thus,', the, 'FANC', pathway, is, a, promising, new, therapeutic]), verbo([target]), complemento([in, melanoma, treatment])]). relacion([sujeto(['These', species, may]), verbo([act]), complemento([as, vectors, 'and/or', potential, vectors, of, many, pathogens, '(', 'virus,', bacteria, and, 'protozoa)'])]). relacion([sujeto(['Their', correct, identification, is, important, to]), verbo([target]), complemento([the, vectors, involved, in, the, transmission, of, the, pathogens, and, also, helps, in, the, fly, control, program])]). relacion([sujeto(['(', -, ')', -, 'Gossypol-loaded', 'Pluronic', 'P85', was]), verbo([found]), complemento([to, be, a, more, potent, radiosensitizer, in, vitro])]). relacion([sujeto(['Pluronic', 'P85']), verbo([increased]), complemento([the, 'anti-proliferative', activity, of, '(', -, ')', -, gossypol, against, 'A549', cells, '(', 82, ±, 42, versus, 190, ±, 60, 'nM)'])]). relacion([sujeto(['In', 'addition,', the, combination, of, 'P85', and, '(', -, ')', -, gossypol, effectively, reduced, clonogenic, survival, of, 'A549', 'cells:', '(', 11, ±, 5, '%', ')', compared, to, '(', -, ')', -, gossypol, and, 'P85', alone, '(', 62, ±, 27, '%', and, 93, ±, 13, '%', ',', 'respectively),', and]), verbo([enhanced]), complemento([radiation, cancer, cell, killing])]). relacion([sujeto(['In', 'vivo,', 'P85', '(', 200, 'mg/kg/day)', and, '(', -, ')', -, gossypol, '(', 15, 'mg/kg/day)', could, be, safely, injected, intravenously, over, 5, days, and]), verbo([enhanced]), complemento(['radiation-related', tumor, control, in, an, 'A549', xenograft, model])]). relacion([sujeto(['Pluronic', 'P85', and, '(', -, ')', -, gossypol]), verbo([act]), complemento([as, a, novel, dual, agent, radiosensitizer, and, holds, promise, as, a, chemoradiotherapeutic, strategy])]). relacion([sujeto(['Mitotic', exit]), verbo([requires]), complemento([the, inactivation, of, 'cyclin-dependent', kinase, '(', 'Cdk)', activity, and, reversal, of, 'Cdk-mediated', phosphorylation, events, by, protein, phosphatases])]). relacion([sujeto(['In', 'Saccharomyces', cerevisiae, the, mitotic, exit, network, '(', 'MEN)']), verbo([leads]), complemento([to, activation, and, dispersal, of, the, 'Cdc14', phosphatase, throughout, the, cell, following, successful, chromosome, segregation])]). relacion([sujeto(['MEN-released', 'Cdc14', is]), verbo([required]), complemento([for, both, full, 'Cdk', inactivation, and, dephosphorylation, of, 'Cdk', substrates])]). relacion([sujeto(['While', 'Cdc14', originally, was, thought, to]), verbo([act]), complemento([broadly, on, mitotic, 'Cdk', 'substrates,', recent, biochemical, studies, revealed, that, 'Cdc14', possesses, a, strong, preference, for, a, subset, of, 'Cdk', phosphorylation, sites])]). relacion([sujeto(['This', intrinsic, specificity, appears, well]), verbo([conserved]), complemento([across, fungi, and, animals])]). relacion([sujeto(['Like', other, 'PTPs,', mutation, of, catalytic, residues, in, the, 'Cdc14', active, site, creates, an, inactive, enzyme, that]), verbo([retains]), complemento([high, affinity, substrate, binding])]). relacion([sujeto(['The', phosphatase, 'Cdc14']), verbo([has]), complemento([a, pivotal, function, in, the, mitotic, exit, of, 'Saccharomyces', cerevisiae])]). relacion([sujeto(['During', 'interphase,', 'Cdc14', remains, inactive, in, the, nucleolus]), verbo([bound]), complemento([to, the, inhibitor, 'Net1'])]). relacion([sujeto(['Cdc14', activation, occurs, in, the, metaphase, to, anaphase, transition, and, it, is]), verbo([promoted]), complemento([by, at, least, two, signaling, pathways, called, 'FEAR', '(', 'CdcFourteen', 'Early', 'Anaphase', 'Release)', and, 'MEN', '(', 'Mitotic', 'Exit', 'Network)'])]). relacion([sujeto(['These', two, pathways]), verbo([act]), complemento([in, parallel, and, target, the, phosphorylation, of, 'Net1,', thus, decreasing, 'Net1', affinity, for, 'Cdc14'])]). relacion([sujeto(['In', contrast, to, heavily, methylated, mammalian, 'genomes,', invertebrate, genomes, are, only, sparsely, methylated, in, a, '\'', 'mosaic\'', fashion, with, the, majority, of, methylated, 'CpG', dinucleotides]), verbo([found]), complemento([across, gene, bodies])]). relacion([sujeto(['Importantly,', this, gene, body, methylation, is, frequently]), verbo([associated]), complemento([with, active, 'transcription,', and, studies, in, the, honeybee, have, shown, that, there, are, strong, links, between, gene, body, methylation, and, alternative, splicing])]). relacion([sujeto(['Among', the, eleven, members, of, the, 'IL-1', family, 'ligands,', precursor, 'IL-1α,', 'IL-1β,', and, 'IL-33']), verbo([have]), complemento([comparatively, long, 'pro-peptides', of, approximately, 110, amino, acid, residues, at, the, 'N-terminus'])]). relacion([sujeto(['However,', the, other, 'IL-1', 'members,', except, for, 'IL-37', '(', also, known, as, 'IL-1F7),']), verbo([have]), complemento([relatively, short, propeptides, with, fewer, than, 40, amino, acid, residues, at, the, 'N-terminus'])]). relacion([sujeto(['Therefore,', soluble, cytokines, readily]), verbo([act]), complemento([on, cell, surface, receptors, immediately, after, their, release, from, cells])]). relacion([sujeto(['Various', processing, enzymes]), verbo([involved]), complemento([in, the, activation, of, intracellular, 'IL-1', family, cytokines, likely, provide, effective, immune, regulation, to, protect, the, host, from, infections])]). relacion([sujeto(['The', family, of, interferon, regulatory, 'factors,', which, includes, nine, mammalian, members, '(', 'IRF1-IRF9),']), verbo([acts]), complemento([as, transcription, factors, for, interferons, and, thus, exerts, regulatory, functions, in, the, immune, system, and, in, oncogenesis])]). relacion([sujeto(['Among', these, 'members,', 'IRF4', expression, is, restricted, to, immune, cells, such, as, 'T', and, 'B', 'lymphocytes,', 'macrophages,', and, dendritic, cells, where, it, is, a, key, factor, in, the, regulation, of, differentiation, and, is]), verbo([required]), complemento([during, the, immune, response, for, lymphocyte, activation, and, the, generation, of, 'immunoglobulin-secreting', plasma, cells])]). relacion([sujeto(['Consequently,', dysregulation, of, 'IRF4', is]), verbo([associated]), complemento([with, many, lymphoid, malignancies])]). relacion([sujeto(['Recent', studies]), verbo([have]), complemento([demonstrated, that, depending, on, the, context, and, stage, of, hematopoietic, cell, differentiation, in, which, its, expression, is, 'dysregulated,', 'IRF4', may, act, as, either, an, oncogene, or, a, 'tumor-suppressor-like', factor])]). relacion([sujeto(['In', 'addition,', it]), verbo([has]), complemento([been, shown, that, 'IRF4', plays, a, pivotal, role, in, the, development, and, function, of, several, 'autoimmune-associated', cells])]). relacion([sujeto(['Various', genetic, and, functional, studies]), verbo([have]), complemento([also, pointed, to, 'IRF4', as, a, master, regulator, for, autoimmunity])]). relacion([sujeto(['We', determined, the, proportion, of, exposed, infants, who, developed, adverse, 'events,', including, 'death,', hypotension]), verbo([requiring]), complemento(['pressors,', 'hyperkalemia,', and, elevated, serum, creatinine])]). relacion([sujeto(['The', alteration, of, the, vascular, system, in, the, victim, after, a, venomous, snake, bite, is, usually]), verbo([expressed]), complemento([by, a, significant, decrease, in, blood, pressure])]). relacion([sujeto(['We', assessed, the, potential, of, the, venom, of, 'Montivipera', 'bornmuelleri,', a, viper, from, 'Lebanon,', to]), verbo([induce]), complemento([relaxant, effect, on, isolated, 'Wistar', rat, aorta, via, several, mechanisms, of, action])]). relacion([sujeto(['By', actions, of, its, metalloproteinases, and, phospholipase, 'A2,', the, venom, may]), verbo([induce]), complemento([the, production, of, nitric, oxide, acting, accordingly, a, vasodilator, effect])]). relacion([sujeto(['It', could]), verbo([act]), complemento([on, the, 'voltage-dependent', potassium, channels, 'and/or', the, 'L-type', calcium, 'channels,', inhibiting, angiotensin, converting, enzyme, 'and/or', inhibiting, the, 'α1-adrenoceptors'])]). relacion([sujeto(['This', work, demonstrates, vasorelaxant, effect, of, the, 'Montivipera', bornmuelleri, venom]), verbo([acting]), complemento([on, different, 'pathways,', reducing, blood, pressure])]). relacion([sujeto(['However,', the, way, in, which, 'one\'s', own, social, status]), verbo([interacts]), complemento([with, 'another\'s', status, to, influence, responses, to, resource, distribution, is, far, from, clear])]). relacion([sujeto(['In', the, current, 'study,', we, dynamically, manipulated, 'participants\'', social, status, and, then, asked, participants, to]), verbo([act]), complemento([as, recipients, in, the, ultimatum, game, '(', 'UG)', along, with, proposers, whose, social, status, was, made, known, to, the, participants])]). relacion([sujeto(['These', findings]), verbo([suggest]), complemento(['that,', in, comparison, with, individuals, in, high, 'status,', individuals, in, low, status, are, more, willing, to, accept, low, offers, during, resource, distribution, and, are, more, affected, by, 'other-status', considerations])]). relacion([sujeto(['By']), verbo([increasing]), complemento([the, proportion, of, open, sites, '(', 'p),', we, describe, a, new, kind, of, threshold, '(', the, &, 'quot;tracking', 'threshold",', approximately, 'pt=0'])]). relacion([sujeto(['We', conclude, that, 'fine-grained', habitats, can]), verbo([act]), complemento([as, &, 'quot;labyrinths"', for, the, plant, within, a, broad, range, of, p, values])]). relacion([sujeto(['Discontinuation', of, omalizumab, was]), verbo([associated]), complemento([with, an, increase, in, free, 'IgE', and, an, increase, in, basophil, expression, of, the, 'high-affinity', 'IgE', receptor])]). relacion([sujeto(['By', pursuing, a, strategy, of, negative, 'reciprocity,', 'BPD', patients, seem, to]), verbo([act]), complemento([mostly, &, 'quot;rationally"', and, in, their, own, 'self-interest'])]). relacion([sujeto(['Their', &, 'quot;grim']), verbo([trigger]), complemento(['strategy"', resembles, the, theoretical, ideal, of, the, rational, and, 'self-interested', agent, homo, economicus])]). relacion([sujeto(['Vitamin', 'D', deficiency, is, common, in, children, with, 'asthma,', and, it]), verbo([associates]), complemento([with, poor, asthma, 'control,', reduced, forced, expiratory, volume, in, one, second, '(', 'FEV1)', and, increased, requirement, for, inhaled, corticosteroids, '(', 'ICS)'])]). relacion([sujeto(['Linear', regression, was, used, to, identify, environmental, and, genetic, factors, independently]), verbo([associated]), complemento([with, serum, 25, '(', 'OH)D', 'concentration,', and, to, determine, whether, vitamin, 'D', status, was, independently, associated, with, 'Asthma', 'Control', 'Test', '(', 'ACT)', 'score,', 'ICS', 'dose,', 'FeNO,', forced, vital, capacity, '(', 'FVC),', 'FEV1', or, lower, airway, eosinophilia])]). relacion([sujeto(['Lower', vitamin, 'D', status, was]), verbo([associated]), complemento([with, higher, body, mass, index, '(', 'P=0'])]). relacion([sujeto(['Vitamin', 'D', status, was, not]), verbo([found]), complemento([to, associate, with, any, marker, of, asthma, control, investigated])]). relacion([sujeto(['However,', in, contrast, to, studies, conducted, in, 'children,', we]), verbo([found]), complemento([no, association, between, vitamin, 'D', status, and, markers, of, asthma, severity, or, control])]). relacion([sujeto(['To', facilitate, the]), verbo([targeting]), complemento([of, axonal, endings, for, 'SCI', 'repair,', this, review, focuses, on, dissecting, the, different, types, of, axonal, endings, present, following, injury, by, examining, them, in, the, context, of, the, 'temporal,', degenerative, and, regenerative, changes, that, occur, following, injury])]). relacion([sujeto(['The', current, understanding, of, the, mechanisms, that]), verbo([lead]), complemento([to, the, development, of, different, types, of, axonal, 'endings,', how, different, experimental, therapeutic, interventions, may, act, on, different, types, of, axonal, 'endings,', the, current, gaps, in, understanding, the, sites, of, action, of, some, 'pro-regenerative', 'therapies,', and, some, of, the, methodological, challenges, to, studying, different, types, of, axonal, endings, are, discussed])]). relacion([sujeto(['Phenylethanol', '(', 'PEtOH)', is, a, constituent, of, essential, oils, with, a, pleasant, odor, and, can]), verbo([act]), complemento([as, a, local, anesthetic])]). relacion([sujeto(['In', this, 'work,', we]), verbo([have]), complemento([explored, the, effect, of, 'PEtOH', on, the, function, of, the, hippocampal, serotonin1A, 'receptor,', a, representative, neurotransmitter, receptor, belonging, to, the, 'G', 'protein-coupled', receptor, '(', 'GPCR)', family])]). relacion([sujeto(['Our', results, show, that, 'PEtOH']), verbo([induces]), complemento([reduction, in, ligand, binding, to, the, serotonin1A, receptor, due, to, lowering, of, binding, 'affinity,', along, with, a, concomitant, decrease, in, the, degree, of, 'G-protein', coupling])]). relacion([sujeto(['Analysis', of, membrane, order, using, the, 'environment-sensitive', fluorescent, probe, 'DPH', revealed]), verbo([decrease]), complemento([in, membrane, order, with, increasing, 'PEtOH', 'concentration,', as, evident, from, reduction, in, rotational, correlation, time, of, the, probe])]). relacion([sujeto(['HCC', was]), verbo([induced]), complemento([in, male, 'Wistar', rats, with, 'N-nitrosodiethylamine', added, to, drinking, water, '(', 100, 'mg/L)', for, 8, weeks])]). relacion([sujeto(['Combination', of, these, two, agents, could]), verbo([act]), complemento([beneficially, or, synergistically, via, two, different, modes, of, action, to, fight, 'HCC'])]). relacion([sujeto(['OVs', specifically, replicate, in, tumor, cells, and, initiate, cell, lysis, whilst, tumor, cells]), verbo([act]), complemento([as, endogenous, bioreactors, for, virus, amplification])]). relacion([sujeto(['Multiple', oxysterols, '(', 'OHCs)']), verbo([have]), complemento([demonstrated, the, ability, to, act, as, agonists, or, antagonists, of, the, hedgehog, '(', 'Hh)', signaling, 'pathway,', a, developmental, signaling, pathway, that, has, been, implicated, as, a, potential, therapeutic, target, in, a, variety, of, human, diseases])]). relacion([sujeto(['These', 'OHCs', are, known, to]), verbo([modulate]), complemento(['Hh', signaling, through, direct, binding, interactions, with, the, 'N-terminal', cysteine, rich, domain, '(', 'CRD)', of, 'Smoothened,', a, key, regulator, of, 'Hh', signal, transduction])]). relacion([sujeto(['Homology', 'modeling,', molecular, dynamics, 'simulations,', and, 'MM/GBSA', energy, calculations, were, utilized, to, explore]), verbo([binding]), complemento([interactions, between, the, 'OHC', scaffold, and, the, human, 'Smoothened', 'CRD'])]). relacion([sujeto(['Calculated', 'MM/GBSA']), verbo([binding]), complemento([energies, for, 'OHCs', in, complex, with, the, 'CRD', of, 'Smoothened', correlate, well, with, in, vitro, 'Hh', modulatory, activity])]). relacion([sujeto(['Computational', modeling, and, molecular, dynamics, simulations, can, be, used, to, predict, whether, a, small, molecule, that]), verbo([binds]), complemento([the, 'Smoothened', 'CRD', will, be, an, agonist, or, antagonist, of, the, pathway])]). relacion([sujeto(['Acetylsalicylic', acid, '(', 'ASA)', is, mainly]), verbo([recognized]), complemento([as, painkiller, or, 'anti-inflammatory', drug])]). relacion([sujeto(['However,', 'ASA']), verbo([causes]), complemento([serious, side, effects, towards, gastrointestinal, '(', 'GI)', tract, which, limits, its, usefulness])]). relacion([sujeto(['Carbon', monoxide, '(', 'CO)', and, hydrogen, sulfide, '(', 'H2S)']), verbo([have]), complemento([been, described, to, act, as, important, endogenous, messengers, and, mediators, of, gastroprotection, but, whether, they, can, interact, in, gastroprotection, against, acute, 'ASA-induced', gastric, damage, remains, unknown])]). relacion([sujeto(['Protein', 'and/or', mRNA, expression, for, 'cystathionine-γ-lyase', '(', 'CSE),', 'cystathionine-β-synthase', '(', 'CBS),', 3, -, mercaptopyruvate, sulfurtransferase, '(', 3, -, 'MST),', heme, oxygenase, '(', 'HO)-1,', 'HO-2,', hypoxia, inducible, 'factor-alpha', '(', 'HIF)-1α,']), verbo([nuclear]), complemento([factor, '(', 'erythroid-derived', 2, ')', -, like, 2, '(', 'Nrf-2),', cyclooxygenase, '(', 'COX)-1', and, 'COX-2,', inducible, nitric, oxide, synthase, '(', 'iNOS)', and, interleukin, '(', 'IL)-1β', were, determined, by, 'Western', blot, or, 'real-time', 'PCR,', respectively])]). relacion([sujeto(['ASA']), verbo([caused]), complemento([hemorrhagic, gastric, mucosal, damage, and, significantly, decreased, 'GBF,', 'H2S', 'production,', 'CO', 'content,', mRNA, or, protein, expression, for, 'CSE,', 3, -, 'MST,', 'HO-2', and, increased, mRNA, 'and/or', protein, expression, for, 'CBS,', 'HO-1,', 'Nrf-2,', 'HIF-1α,', 'iNOS,', 'IL-1β,', 'COX-2', in, gastric, mucosa, and, 'COHb', concentration, in, blood])]). relacion([sujeto(['Pretreatment', with, 'CORM-2', or, 'NaHS', but, not, with, 'PAG']), verbo([decreased]), complemento(['ASA-damage', and, increased, 'GBF'])]). relacion([sujeto(['CORM-2', elevated, 'CO', 'content,', mRNA, or, protein, expression, for, 'HO-1,', 'Nrf-2,', and]), verbo([decreased]), complemento([expression, of, 'CBS,', 'HIF-1α,', 'COX-2,', 'IL-1β,', 'iNOS,', the, 'H2S', production, in, gastric, mucosa, and, 'COHb', concentration, in, blood])]). relacion([sujeto(['NaHS', raised, mRNA, or, protein, expression, for, 'CSE,', 'COX-1', and]), verbo([decreased]), complemento([mRNA, expression, for, 'IL-1β', and, 'COHb', level, in, blood])]). relacion([sujeto(['We', conclude, that, 'CO', is]), verbo([involved]), complemento([in, gastroprotection, induced, by, 'H2S', while, beneficial, protective, action, of, 'CO', released, from, 'CORM-2', in, gastric, mucosa, seems, to, be, 'H2S-independent'])]). relacion([sujeto(['In', contrast, to, 'H2S,', 'CO', ameliorates, 'hypoxia,']), verbo([regulates]), complemento(['Nrf-2', expression, but, similarly, to, 'H2S', acts, on, 'sGC-dependent', manner, to, restore, gastric, microcirculation, and, exhibit, 'anti-inflammatory', activity, in, gastric, mucosa, compromised, by, 'ASA'])]). relacion([sujeto(['RT-qPCR', is, a, sensitive, and, highly, efficient, technique, that, is, widely, used, in, gene, expression, analysis, and, to]), verbo([provide]), complemento([insight, into, the, molecular, mechanisms, underlying, embryonic, development])]). relacion([sujeto(['This', study]), verbo([provides]), complemento([suitable, reference, genes, for, 'RT-qPCR', analysis, and, allows, future, studies, of, the, gene, expression, in, 'M'])]). relacion([sujeto(['Although', an, essential, molecule, for, several, biological, 'processes,', its, excess, can]), verbo([lead]), complemento([to, oxidative, stress])]). relacion([sujeto(['These', evolutionarily]), verbo([conserved]), complemento([proteins, regulate, iron, homeostasis, by, storing, and, releasing, iron, in, a, controlled, manner])]). relacion([sujeto(['Our', data]), verbo([has]), complemento([shown, that, silencing, ferritin, 1, alters, tick, competence, to, normally, engorge, and, causes, morphologic, and, histochemical, changes, in, the, ovaries, '(', 'OV)', and, oocytes])]). relacion([sujeto([canis, 'DNA', was]), verbo([found]), complemento([in, either, experimental, group])]). relacion([sujeto(['Determining', the, function, of, molecules, that]), verbo([act]), complemento([in, key, biological, 'processes,', such, as, blood, digestion, or, 'reproduction,', and, that, could, be, considered, potential, tick, antigens, will, contribute, towards, the, improvement, of, current, control, measures, against, these, ectoparasites, and, the, pathogens, they, vector])]). relacion([sujeto(['Specifically,', we, hypothesize, that, the, broad, diversity, of, behavioral, phenotypes, present, at, 'micro-', and, macroevolutionary, scales, is]), verbo([promoted]), complemento([by, a, disproportionately, large, mutational, target, of, neurogenic, genes])]). relacion([sujeto(['We', present, evidence, that, these, large, 'neuro-behavioral']), verbo([targets]), complemento([are, significant, and, ubiquitous, in, animal, genomes, and, suggest, that, 'behavior\'s', novelty, and, rapid, emergence, are, driven, by, a, number, of, factors, including, more, selection, on, a, larger, pool, of, 'variants,', a, greater, role, of, phenotypic, 'plasticity,', 'and/or', unique, molecular, features, present, in, large, genes])]). relacion([sujeto(['In', 'contrast,', the, large, mutational]), verbo([target]), complemento([hypothesis, places, genomic, architecture, and, a, larger, allelic, pool, at, the, forefront, of, rapid, evolutionary, 'change,', particularly, in, genetic, systems, that, are, polygenic, and, regulatory, in, nature])]). relacion([sujeto(['In', mammals, and, 'invertebrates,', neurogenic, genes, harbor, larger, 'protein-coding', regions, and, possess, a, richer, regulatory, repertoire, of, miRNA]), verbo([targets]), complemento([and, transcription, factor, binding, sites])]). relacion([sujeto(['Overall,', neurogenic, genes, cover, a, disproportionately, large, genomic, 'fraction,']), verbo([providing]), complemento([a, sizeable, substrate, for, 'evolutionary,', 'genetic,', and, molecular, mechanisms, to, act, upon])]). relacion([sujeto(['Readily', available, comparative, and, functional, genomic, data]), verbo([provide]), complemento([unexplored, opportunities, to, test, whether, a, distinct, neurogenomic, architecture, can, promote, rapid, behavioral, change, via, several, mechanisms, unique, to, large, 'genes,', and, which, components, of, this, large, footprint, are, uniquely, metazoan])]). relacion([sujeto(['The', large, mutational]), verbo([target]), complemento([hypothesis, highlights, the, eminent, roles, of, mutation, and, functional, genomic, architecture, in, generating, rapid, developmental, and, evolutionary, change])]). relacion([sujeto(['It']), verbo([has]), complemento([broad, implications, on, our, understanding, of, the, genetics, of, complex, adaptive, traits, such, as, behavior, by, focusing, on, the, importance, of, mutational, 'input,', from, 'SNPs', to, alternative, transcripts, to, transposable, 'elements,', on, driving, evolutionary, rates, of, functional, systems])]). relacion([sujeto(['Such', functional, divergence]), verbo([has]), complemento([important, implications, in, promoting, behavioral, isolation, across, 'short-', and, 'long-term', timescales])]). relacion([sujeto(['Due', to, 'genome-scaled', polygenic, 'adaptation,', the, large]), verbo([target]), complemento([effect, also, contributes, to, our, inability, to, identify, adapted, behavioral, candidate, genes])]). relacion([sujeto(['The', large, mutational]), verbo([target]), complemento([hypothesis, can, also, explain, the, rapid, evolution, of, other, functional, systems, covering, a, large, genomic, fraction, such, as, male, fertility, and, its, preferential, association, with, hybrid, male, sterility, among, closely, related, taxa])]). relacion([sujeto(['Overall,', a, focus, on, mutational, potential, may]), verbo([increase]), complemento([our, power, in, understanding, the, genetic, basis, of, complex, phenotypes, such, as, behavior, while, filling, a, general, gap, in, understanding, their, evolution])]). relacion([sujeto(['Histological', evaluation, of, two, bruises, from, a, pig, with, multiple, lesions, was]), verbo([found]), complemento([insufficient, to, assess, the, overall, age, of, the, lesions, as, substantial, variation, in, the, inflammatory, response, between, bruises, was, present])]). relacion([sujeto(['Resistance', to, imatinib]), verbo([has]), complemento([been, recognized, as, a, major, challenge, for, the, treatment, of, chronic, myeloid, leukemia, '(', 'CML)'])]). relacion([sujeto(['Aberrant', expression, of, 'miR-451']), verbo([has]), complemento([been, reported, to, participate, in, anticancer, drug, resistance])]). relacion([sujeto(['However,', the, role, of, 'miR-451', in, imatinib, resistance]), verbo([has]), complemento([not, been, investigated])]). relacion([sujeto(['The', present, study, was, undertaken, to, determine, the, expression, of, 'miR-451', in, order, to]), verbo([find]), complemento([a, possible, association, between, the, expression, of, this, miRNA, and, imatinib, resistance, in, 'Tunisian', 'CML', patients])]). relacion([sujeto(['In', silico, analysis, identified, 'MYC', as, a, potential]), verbo([target]), complemento([of, 'miR-451'])]). relacion([sujeto(['On', the, other, 'hand,']), verbo([increased]), complemento([level, of, 'MYC', was, detected, in, 'imatinib-resistant', 'CML', cases, which, may, explain, the, causative, role, of, 'MYC', in, 'CML', cases, and, the, downregulation, of, 'miR-451'])]). relacion([sujeto(['Taken', 'together,', our, findings]), verbo([suggest]), complemento([that, 'miR-451', and, 'MYC', form, together, a, regulatory, loop, which, may, act, as, a, potential, therapeutic, 'target,', and, disruption, of, suggested, regulatory, loop, could, help, to, improve, 'CML', therapy])]). relacion([sujeto(['Reactive', astrogliosis]), verbo([has]), complemento([been, occurred, after, intracerebral, hemorrhage, '(', 'ICH)'])]). relacion([sujeto(['Leukemia', inhibitory, factor, '(', 'LIF)', can]), verbo([act]), complemento([as, a, modulator, for, glial, gene, expression])]). relacion([sujeto(['The', present, study, tested, whether, endogenous, leukemia, inhibitory, factor, '(', 'LIF)']), verbo([acted]), complemento([on, intracerebral, hemorrhage, '(', 'ICH)-induced', reactive, astrogliosis, via, 'STAT3', signaling, pathway])]). relacion([sujeto(['Brains', were, perfused, to, identify, proliferating, cell]), verbo([nuclear]), complemento([antigen, '(', 'PCNA)+/glial', fibrillary, acidic, protein, '(', 'GFAP)+nuclei'])]). relacion([sujeto(['Moreover,', 'LIF']), verbo([increased]), complemento([the, number, of, 'PCNA+/GFAP+', nuclei, and, the, expression, of, 'GFAP,', 'LIFR,', 'gp130,', and, 'p-STAT3'])]). relacion([sujeto(['Together,', these, data]), verbo([suggest]), complemento([that, 'LIF', contributes, to, 'ICH-related', reactive, astrogliosis, via, activation, of, 'STAT3', signaling])]). relacion([sujeto(['Autophagy', is, a]), verbo([conserved]), complemento([cellular, 'self-digestion', pathway, for, maintenance, of, homeostasis, under, basal, and, stressed, conditions])]). relacion([sujeto(['Of', special, note, is, that, accumulating, data]), verbo([suggest]), complemento([an, intimate, relationship, between, autophagy, and, ovarian, carcinoma])]). relacion([sujeto(['Autophagy', is, well, identified, to]), verbo([act]), complemento([as, either, as, a, 'tumor-suppressor', or, as, a, 'tumor-promoter', in, ovarian, carcinoma])]). relacion([sujeto(['However,', the, mechanism, underlying, autophagy]), verbo([associated]), complemento([with, ovarian, carcinoma, remains, 'elusive,', the, precise, role, of, autophagy, in, ovarian, carcinoma, also, remains, undetermined])]). relacion([sujeto(['The', antimicrobial, property, of, silver, is]), verbo([associated]), complemento([to, the, quantity, of, silver, and, the, grade, of, silver, released])]). relacion([sujeto(['The', ionized, silver, is, extremely, 'sensitive,', as, it]), verbo([binds]), complemento([to, tissue, proteins, and, gets, operational, alterations, in, the, bacterial, cell, wall, and, nuclear, membrane, leading, to, cell, modification, and, death])]). relacion([sujeto(['Silver', nanoparticles]), verbo([have]), complemento([the, talent, to, anchor, to, the, bacterial, cell, wall, and, consequently, infiltrate, 'it,', so, causing, physical, modifications, in, the, cell, membrane, like, the, absorptivity, of, the, cell, membrane, and, death, of, the, cell])]). relacion([sujeto(['There', are, numerous, concepts, on, the]), verbo([act]), complemento([of, silver, nanoparticle, on, bacteria, to, reason, the, microbicidal, influence])]). relacion([sujeto(['They']), verbo([act]), complemento([fast, and, efficient, to, suppress, inflammation, and, serve, to, bridge, the, gap, until, disease, modifying, drugs, '(', 'DMARD)', show, effect])]). relacion([sujeto(['To', cope, with, heterogeneous, environments, and, resource, 'distributions,', filamentous, fungi]), verbo([have]), complemento([evolved, a, spatially, extensive, growth, enabling, their, hyphae, to, penetrate, 'air-water', interfaces, and, pass, through, 'air-filled', pores])]). relacion([sujeto(['Such', mycelia, are, also, known, to]), verbo([act]), complemento([as, dispersal, networks, for, the, mobilisation, of, bacteria, '(', '\'', fungal, 'highways\')', and, connection, of, microbial, microhabitats])]). relacion([sujeto(['Our', data, give, evidence, that, hyphae]), verbo([increase]), complemento([the, accessibility, of, the, prey, to, 'B'])]). relacion([sujeto(['Our', data]), verbo([suggest]), complemento([that, mycelia, have, substantial, influence, on, 'prey-predator', relationship, and, hereby, may, promote, the, structure, of, prey, and, predator, populations, 'and,', 'hence,', may, be, a, determinant, for, biomass, formation, in, heterogeneous, environments])]). relacion([sujeto(['The', 'RhoA', and, 'RhoC', 'GTPases']), verbo([act]), complemento([via, the, 'ROCK1', and, 'ROCK2', kinases, to, promote, actomyosin, 'contraction,', resulting, in, directly, induced, changes, in, cytoskeleton, structures, and, altered, gene, transcription, via, several, possible, indirect, routes])]). relacion([sujeto(['Elevated', activation, of, the, 'Rho/ROCK', pathway]), verbo([has]), complemento([been, reported, in, several, diseases, and, pathological, 'conditions,', including, disorders, of, the, central, nervous, 'system,', cardiovascular, dysfunctions, and, cancer])]). relacion([sujeto(['To', determine, how]), verbo([increased]), complemento(['ROCK', signalling, affected, gene, expression, in, pancreatic, ductal, adenocarcinoma, '(', 'PDAC)', 'cells,', we, transduced, mouse, 'PDAC', cell, lines, with, retroviral, constructs, encoding, fusion, proteins, that, enable, conditional, activation, of, 'ROCK1', or, 'ROCK2,', and, subsequently, performed, 'RNA', sequencing, '(', 'RNA-Seq)', using, the, 'Illumina', 'NextSeq', 500, platform])]). relacion([sujeto(['Activation', of, 'ROCK1', or, 'ROCK2', signalling]), verbo([induced]), complemento([significant, changes, in, gene, expression, that, could, be, used, to, determine, how, actomyosin, contractility, influences, gene, transcription, in, pancreatic, cancer])]). relacion([sujeto(['Current', attempts, at, gene, therapy, for, 'FH']), verbo([have]), complemento([been, limited, by, the, use, of, strong, heterologous, promoters, which, lack, genomic, 'DNA', elements, essential, for, regulated, expression])]). relacion([sujeto(['Here,', we]), verbo([have]), complemento([combined, a, 'mini-gene', vector, expressing, the, human, 'LDLR', cDNA, from, a, 10, kb, native, human, 'LDLR', locus, genomic, 'DNA', promoter, 'element,', with, an, efficient, miRNA, targeting, 3, -, 'hydroxy-3-methylgutaryl-coenzyme', 'A', reductase, '(', 'Hmgcr),', to, further, enhance, 'LDLR', expression])]). relacion([sujeto(['We', show, that, the, combined, vector]), verbo([suppresses]), complemento([endogenous, 'Hmgcr', transcripts, in, 'vivo,', leading, to, an, increase, in, 'LDLR', transgene, expression])]). relacion([sujeto(['Taken', 'together,', the, vector, system, we, describe, exploits, the, normal, cellular, regulation, of, the, 'LDLR', to]), verbo([provide]), complemento([prolonged, expression, of, 'LDLR', through, targeted, knockdown, of, 'Hmgcr'])]). relacion([sujeto(['This', novel, gene, therapy, system, could]), verbo([act]), complemento(['alone,', or, in, synergy, with, current, therapies, that, modulate, intracellular, 'cholesterol,', such, as, 'statins,', greatly, enhancing, its, therapeutic, application, for, 'FH'])]). relacion([sujeto(['Background', 'A', recent, clinical, trial]), verbo([has]), complemento([shown, a, beneficial, effect, of, the, antioxidant, agent, selenium, in, 'Graves\'', orbitopathy, '(', 'GO)'])]). relacion([sujeto(['Cells', were, treated, with, 'H2O2', to]), verbo([induce]), complemento([oxidative, 'stress,', after, 'pre-incubation', with, 'selenium-(Methyl)selenocysteine', '(', 'SeMCys)'])]). relacion([sujeto(['Results', 'H2O2']), verbo([induced]), complemento([an, increase, in, cell, 'GSSG', and, fibroblast, 'proliferation,', which, were, reduced, by, 'SeMCys'])]). relacion([sujeto(['Incubation', of, 'H2O2-treated', cells, with, 'SeMCys', was, followed, by, an]), verbo([increase]), complemento([in, glutathione, peroxidase, 'activity,', one, of, the, antioxidant, enzymes, into, which, selenium, is, incorporated])]). relacion([sujeto(['H2O2', determined, an]), verbo([increase]), complemento([in, endogenous, cytokines, involved, in, the, response, to, oxidative, stress, and, 'GO', 'pathogenesis,', namely, 'TNF-alpha,', 'IL1-beta', and, 'IFN-gamma'])]). relacion([sujeto(['The']), verbo([increases]), complemento([in, 'TNF-alpha', and, 'IFN-gamma', 'were', rescued, by, 'SeMCys'])]). relacion([sujeto(['Conclusions', 'Selenium,', in, the, form, of, 'SeMCys,', rescues, from, some, of, the, effects, of, oxidative, stress, in, orbital, 'fibroblasts,', namely]), verbo([increased]), complemento([proliferation, and, 'pro-inflammatory', cytokines])]). relacion([sujeto(['SeMCys', reduces, 'HA']), verbo([release]), complemento([in, 'GO', fibroblasts, in, a, manner, that, seems, at, least, in, part, independent, from, 'H2O2-induced', oxidative, stress])]). relacion([sujeto(['Our', findings]), verbo([reveal]), complemento([some, cellular, mechanisms, by, which, selenium, may, act, in, patients, with, 'GO'])]). relacion([sujeto(['In', recent, 'times,', a, particular, attention]), verbo([has]), complemento([been, devoted, to, bacterial, biopolymer, '(', 'polyesters)', such, as, intracellular, polyhydroxyalkanoates, '(', 'PHAs)', produced, by, 'sponge-associated', bacteria])]). relacion([sujeto(['Bacterial', 'PHAs']), verbo([act]), complemento([as, an, internal, reserve, for, carbon, and, energy, and, also, are, a, tremendous, alternative, for, fossil, 'fuel-based', polymers, mainly, due, to, their, 'eco-friendliness'])]). relacion([sujeto(['In', this, 'review,', we]), verbo([have]), complemento([emphasized, the, industrial, prospects, of, marine, bacteria, for, the, commercial, production, of, 'PHAs', and, special, importance, has, been, given, to, marine, 'sponge-associated', bacteria, as, a, potential, resource, for, 'PHAs'])]). relacion([sujeto(['In', the, late, 1930, 's,', 'Karl', von, 'Frisch']), verbo([reported]), complemento([that, semiochemicals, released, upon, 'injury,', act, as, alarm, substances, '(', 'Schreckstoff)', in, fish])]). relacion([sujeto(['In', 'Ostariophysi', 'species,', club, cells, in, the, epidermis, are, believed, to, contain, cues, related, to, alarm, 'substance;', 'however,', the, function, of, club, 'cells,', primarily, as, reservoirs, of, alarm, substance]), verbo([has]), complemento([been, debated])]). relacion([sujeto(['The', response, to, alarm, substance, '(', 'Schreckreaction)', in, medaka, is, characterized, by, bouts, of, immobility, and, an]), verbo([increase]), complemento([in, cortisol, levels, within, minutes, of, exposure, to, conspecific, skin, extract])]). relacion([sujeto(['Histological', 'analysis,', 'however,']), verbo([suggests]), complemento([that, club, cells, are, either, rare, or, absent, in, the, medaka, epidermis])]). relacion([sujeto(['To']), verbo([gain]), complemento([access, to, the, human, red, blood, 'cell,', these, proteins, must, cross, the, parasitophorous, 'vacuole,', a, membrane, bound, compartment, surrounding, the, parasite, that, is, generated, during, the, invasion, process])]). relacion([sujeto(['We', recently]), verbo([reported]), complemento([the, unexpected, finding, of, a, 'species-restricted', 'parasite-encoded', 'Hsp70,', termed, 'PfHsp70x,', which, is, exported, into, the, host, erythrocyte, cytosol])]). relacion([sujeto(['PfHsp70x', lacks, a, classical, 'PEXEL/HT', 'motif,', and, its, transport, appears, to, be]), verbo([mediated]), complemento([by, a, 7, amino, acid, motif, directly, following, the, hydrophobic, 'N-terminal', secretory, signal])]). relacion([sujeto(['In', this, 'report,', we, analyse, this, short]), verbo([targeting]), complemento([sequence, in, detail])]). relacion([sujeto(['Surprisingly,', both, a, reversed, and, scrambled, version, of, the, motif]), verbo([retained]), complemento([the, capacity, to, confer, protein, export])]). relacion([sujeto(['Site', directed, mutagenesis, of, glutamate, residues, within, this, region]), verbo([leads]), complemento([to, a, block, of, protein, trafficking, within, the, lumen, of, the, 'PV'])]). relacion([sujeto(['In', contrast, to, 'PEXEL-containing', 'proteins,', the]), verbo([targeting]), complemento([signal, is, not, 'cleaved,', but, appears, to, be, acetylated])]). relacion([sujeto(['Furthermore', we, show, 'that,', like, other, exported, 'proteins,', trafficking, of, 'PfHsp70x']), verbo([requires]), complemento([the, vacuolar, 'translocon,', 'PTEX'])]). relacion([sujeto(['In', this, 'study,', we, observed, the, peak, splitting, of, absorption, spectra, for, 'two-dimensional', sheets, of, silver, nanoparticles, due, to, the, electromagnetically]), verbo([induced]), complemento([transparency, '(', 'EIT)', effect])]). relacion([sujeto(['The', 'Ag', nanosheets, used, in, this, study, can]), verbo([act]), complemento([as, a, plasmonic, metamaterial, light, 'absorber,', which, has, a, such, large, oscillator, strength])]). relacion([sujeto(['This', phenomenon, is, a, fundamental, optical, property, of, a, thin, film, on, a, metal, substrate, but]), verbo([has]), complemento([never, been, observed, because, native, materials, do, not, have, a, large, oscillator, strength])]). relacion([sujeto(['Propofol', and, etomidate, are, the, most, important, intravenous, general, anesthetics, in, the, current, clinical, use, and, that]), verbo([mediate]), complemento(['gamma-aminobutyric', 'acid\'s', '(', 'GABAergic)', synaptic, transmission])]). relacion([sujeto(['However,', their, 'long-term', effects, on, 'GABAergic', synaptic, transmission]), verbo([induced]), complemento([by, neonatal, propofol, or, etomidate, exposure, remain, unclear])]). relacion([sujeto(['Neonatal', propofol, exposure, significantly]), verbo([increased]), complemento([the, frequency, of, mIPSCs, '(', from, 1.87, ±, 0.35, 'Hz', to, 3.43, ±, 0.51, 'Hz,', 'P<', 0.05, ')', and, did, not, affect, the, amplitude, of, mIPSCs, and, sIPSCs])]). relacion([sujeto(['Bumetanide', significantly, blocked, the, frequency]), verbo([increase]), complemento([and, reversed, the, kinetic, alteration, of, mIPSCs, induced, by, neonatal, propofol, exposure, '(', 3.01, ±, 0.45, 'Hz', and, 94.3, ±, 32.56, 'ms)'])]). relacion([sujeto(['Neonatal', propofol, and, etomidate, exposure]), verbo([has]), complemento(['long-term', effects, on, inhibitory, 'GABAergic', transmission])]). relacion([sujeto(['Propofol', might]), verbo([act]), complemento([at, 'pre-', and, 'post-synaptic', 'GABA', receptor, 'A', '(', 'GABAA)', receptors, within, 'GABAergic', synapses, and, impairs, the, glutamatergic, tonic, input, to, 'GABAergic', 'synapses;', etomidate, might, act, at, the, postsynaptic, site])]). relacion([sujeto(['The', striped, stem, 'borer,', 'Chilo', 'suppressalis,', is, a, major]), verbo([target]), complemento([pest, of, transgenic, rice, expressing, the, 'Cry1Ab', protein, from, the, bacterium, 'Bacillus', thuringiensis, '(', 'Bt)', in, 'China'])]). relacion([sujeto(['Since', 'Bt', exerts, its, activity, through]), verbo([binding]), complemento([to, specific, receptors, in, the, midgut, of, target, 'insects,', identification, of, functional, 'Cry1Ab', receptors, in, the, midgut, of, 'C'])]). relacion([sujeto(['Down-regulating', the, expression, of, 'CsAPNs', by, 'RNAi', was, closely]), verbo([associated]), complemento([with, reduced, susceptibility, of, 'C'])]). relacion([sujeto(['These', data]), verbo([provide]), complemento([the, first, direct, evidence, that, 'CsAPNs', participate, in, the, mode, of, 'Cry1Ab', action, and, may, act, as, the, functional, receptor, of, 'Cry1A', in, 'C'])]). relacion([sujeto(['In', this, 'regard,', renewed, interest, is, growing, in, the, last, years, for, the, consideration, that, the, brain, 'RAAS', could, represent, a, new, important, therapeutic]), verbo([target]), complemento([to, regulate, not, only, the, blood, pressure, via, central, nervous, 'control,', but, also, neurological, diseases])]). relacion([sujeto(['However,', the, development, of, compounds, able, to, cross, the, 'blood-brain', barrier, and, to]), verbo([act]), complemento([on, the, brain, 'RAAS', is, 'challenging,', especially, if, the, metabolic, stability, and, the, 'half-life', are, taken, into, consideration])]). relacion([sujeto(['To', 'date,', two, drug, classes, '(', aminopeptidase, type, 'A', inhibitors, and, angiotensin, 'IV', 'analogues)']), verbo([acting]), complemento([on, the, brain, 'RAAS', are, in, development, in, 'pre-clinical', or, clinical, stages])]). relacion([sujeto(['In', this, 'article,', we, will, present, an, overview, of, the, biological, functions, played, by, peripheral, and, brain, classic, and, 'non-classic', pathways, of, the, 'RAAS', in, several, clinical, 'conditions,', focusing, on, the, brain, 'RAAS', and, on, the, new, pharmacological]), verbo([targets]), complemento([of, the, 'RAAS'])]). relacion([sujeto(['Diabetic', patients, receiving, care, from, 'APPs', were, statistically, more, likely, to]), verbo([have]), complemento([glycemic, '(', 50, '%', vs, 51.4, '%', ',', odds, ratio, '[', 'OR]', 1.06, '[', 1.05, -, 1.08, ']', ')', and, 'BP', control, '(', 77.5, '%', vs, 78.4, '%', ',', 'OR', 1.04, '[', 1.03, -, 1.06, ']', ')', ',', whereas, patients, receiving, care, from, physicians, were, more, likely, to, have, cholesterol, control, '(', receipt, of, statin, 68, '%', vs, 66.5, '%', ',', 'OR', 0.94, '[', 0.93, -, 0.95, ']', ')', in, adjusted, 'models,', although, these, differences, are, not, clinically, significant])]). relacion([sujeto(['Sophoraflavanone', 'G', '(', 'SG),', a, major, flavonoid]), verbo([found]), complemento([in, the, 'S'])]). relacion([sujeto(['alopecuroides,']), verbo([has]), complemento([also, been, reported, to, exhibit, 'anti-inflammatory', activity, both, in, vitro, and, in, vivo])]). relacion([sujeto([alopecuroides, and, 'SG', on, 'microglia-mediated', neuroinflammation]), verbo([has]), complemento([not, been, investigated])]). relacion([sujeto([alopecuroides, extract, '(', 'SAE)', and, 'SG']), verbo([inhibited]), complemento([the, 'LPS-induced', release, of, nitric, oxide, '(', 'NO),', prostaglandin, 'E2', '(', 'PGE2),', tumor, necrosis, 'factor-α', '(', 'TNF-α),', 'interleukin-6', '(', 'IL-6)', and, 'interleukin-1β', '(', 'IL-1β)'])]). relacion([sujeto(['Additionally,', 'SG', reduced, gene, expressions, of, inducible, nitric, oxide, synthase, '(', 'iNOS),', 'cyclooxygenase-2', '(', 'COX-2),', 'TNF-α,', 'IL-6', and, 'IL-1β,', and, further]), verbo([decreased]), complemento([the, protein, expressions, of, iNOS, and, 'COX-2'])]). relacion([sujeto(['Mechanism', studies]), verbo([found]), complemento([that, 'SG', 'down-regulated', phosphorylated, 'mitogen-activated', protein, kinases, '(', 'MAPKs),', 'phosphoinositide-3-kinase', '(', 'PI3K)/AKT', and, 'Janus', 'kinase/signal', transducer, and, activator, of, transcription, '(', 'JAK/STAT),', and, 'up-regulated', heme, 'oxygenase-1', '(', 'HO-1)', expression, via, nuclear, translocation, of, nuclear, factor, 'E2-related', factor, 2, '(', 'Nrf2)'])]). relacion([sujeto(['In', 'addition,', 'SG']), verbo([inhibited]), complemento([the, cytotoxicity, of, conditioned, medium, prepared, by, 'LPS-activated', 'BV2', microglia, to, neuronal, 'PC12', cells, and, improved, cell, viability])]). relacion([sujeto(['SG', was, able, to]), verbo([inhibit]), complemento([the, neuroinflammation, by, 'MAPKs,', 'PI3K/AKT,', 'JAK/STAT', and, 'Nrf2/HO-1', signaling, pathways, and, might, act, as, a, natural, therapeutic, agent, to, be, further, developed, for, the, treatment, of, various, neuroinflammatory, conditions])]). relacion([sujeto(['Hence,', only, selenite, can]), verbo([act]), complemento([as, an, 'oxidant,', particularly, in, the, reaction, with, free, 'and/or', 'protein-bound', sulhydryl, '(', 'SH)', groups])]). relacion([sujeto(['For', 'example,', selenite, was, shown, to]), verbo([inhibit]), complemento([the, hydroxyl, 'radical-induced', reduction, and, scrambled, reoxidation, of, disulfides, in, human, fibrinogen, thus, preventing, the, formation, of, highly, hydrophobic, 'polymer,', termed, parafibrin])]). relacion([sujeto(['Such', a, 'polymer,', when, deposited, within, peripheral, 'and/or', cerebral, 'circulation,', may]), verbo([cause]), complemento([irreversible, damage, resulting, in, the, development, of, 'cardiovascular,', neurological, and, other, degenerative, diseases])]). relacion([sujeto(['Aimed', at, approved, mental, health, professionals, and, others, working, in, this, 'area,', this, updated, issue]), verbo([provides]), complemento([a, quick, and, easy, guide, to, mental, health, act, assessments, and, surrounding, legal, frameworks])]). relacion([sujeto(['We']), verbo([report]), complemento([on, the, mechanism, by, which, 'HSCs', attain, cycling, quiescence, by, addressing, a, role, for, inducible, cyclic, 'AMP', early, repressor, '(', 'ICER)'])]). relacion([sujeto(['These', activators, can, be]), verbo([induced]), complemento([by, hematopoietic, stimulators, such, as, cytokines])]). relacion([sujeto(['Immunoprecipitation', indicated, the, highest, level, of, 'ICER', in, the]), verbo([nuclear]), complemento([extracts, of, 'CD34(+)/CD38(-)', cells])]). relacion([sujeto(['Phospho', '(', 'p)-CREM', was, also, present]), verbo([suggesting]), complemento([a, balance, between, 'ICER', and, 'p-CREM', in, 'HSC'])]). relacion([sujeto(['ICER', seems, to, be, responsible, for]), verbo([decrease]), complemento([in, 'G1', 'transition,', based, on, reduced, 'Cdk4', 'protein,', decreased, proliferation, and, functional, studies, with, propidium, iodide])]). relacion([sujeto(['There', were, no, marked, changes, in, the, cycling, 'inhibitors,', p15, and, 'p-Rb,']), verbo([suggesting]), complemento([that, 'ICER', may, act, independently, of, other, cycling, inhibitors])]). relacion([sujeto(['These', findings, are, relevant, to, gene, therapy, that]), verbo([require]), complemento([engineering, of, 'HSCs,', 'age-related', disorders, that, are, associated, with, hematopoietic, dysfunction, and, other, hematological, disorders])]). relacion([sujeto(['Emulsion', droplets]), verbo([act]), complemento([as, very, numerous, small, reaction, chambers, in, which, different, 'PCR', products, from, a, single, genomic, 'DNA', molecule, are, condensed, into, short, joint, 'products,', to, unite, sequences, in, cis, from, widely, separated, genomic, sites])]). relacion([sujeto(['These', products, can, therefore]), verbo([provide]), complemento([information, about, the, arrangement, of, sequences, and, variants, at, a, larger, scale, than, established, 'long-read', sequencing, methods])]). relacion([sujeto(['The', method]), verbo([has]), complemento([been, useful, in, defining, the, phase, of, variants, in, 'haplotypes,', the, typing, of, 'inversions,', and, determining, the, configuration, of, sequence, variants, in, multiallelic, 'CNVs'])]). relacion([sujeto(['Cognitive', control, processes, enable, us, to]), verbo([act]), complemento([flexibly, in, a, world, posing, 'ever-changing', demands, on, our, cognitive, system])]). relacion([sujeto(['To', study, cognitive, 'control,', conflict, tasks, and, especially, congruency, sequence, effects]), verbo([have]), complemento([been, regarded, as, a, fruitful, tool])]). relacion([sujeto(['However,', for, the, last, decade, a, dispute]), verbo([has]), complemento([arisen, whether, or, not, congruency, sequence, effects, are, indeed, a, valid, measure, of, cognitive, control, processes])]). relacion([sujeto(['This', debate]), verbo([has]), complemento([led, to, the, development, of, increasingly, complex, paradigms, involving, 'numerous,', intricately, designed, experimental, conditions, which, are, aimed, at, excluding, 'low-level,', associative, learning, mechanisms, like, feature, binding, as, an, alternative, explanation, for, the, emergence, of, congruency, sequence, effects])]). relacion([sujeto(['Here,', we, try, to, go, beyond, this, 'all-or-nothing', thinking, by, investigating, the, assumption, that, both, cognitive, control, processes, as, well, as, feature]), verbo([binding]), complemento([mechanisms, occur, within, trials, of, the, same, task])]). relacion([sujeto(['By', comparing, these, predictions, to, continuous, mouse, movements, from, an, adapted, 'Simon', 'task,', we]), verbo([find]), complemento([evidence, that, control, processes, and, feature, binding, mechanisms, do, indeed, coexist, within, the, task, but, that, they, follow, distinct, timing, patterns])]). relacion([sujeto(['This', study]), verbo([suggests]), complemento([a, limited, influence, of, 'RM', systems, on, the, evolution, of, 'Salmonella', enterica, subsp])]). relacion([sujeto(['Thus,', we, conclude, that, other, factors, must, be]), verbo([involved]), complemento([in, shaping, the, evolution, of, bacteria])]). relacion([sujeto(['Restriction-modification', systems, are, thought, to]), verbo([cause]), complemento([rearrangements, within, the, 'chromosome,', as, well, as, act, as, a, barrier, to, horizontal, gene, transfer])]). relacion([sujeto(['In', 'summary,', from, this, 'work,', we, conclude, that, other, mechanisms, might, be]), verbo([involved]), complemento([in, controlling, and, shaping, the, evolution, of, 'Salmonella', enterica, subsp])]). relacion([sujeto(['A', developmental, program, of, epigenetic, repression, prepares, each, mammalian, olfactory, sensory, neuron, '(', 'OSN)', to, strongly]), verbo([express]), complemento([one, allele, from, just, one, of, hundreds, of, odorant, receptor, '(', 'OR)', 'genes,', but, what, completes, this, process, of, 'OR', gene, choice, by, driving, the, expression, of, this, allele, is, incompletely, understood])]). relacion([sujeto(['Given', previous, evidence, that, 'Lhx2']), verbo([binds]), complemento(['OR', gene, control, 'elements,', these, findings, indicate, that, 'Lhx2', is, directly, involved, in, driving, 'OR', expression])]). relacion([sujeto(['In', contrast, to, the, robust, effects, of, conditional, deletion, of, 'Lhx2,', the]), verbo([loss]), complemento([of, 'Emx2', has, much, smaller, effects, and, more, often, causes, increased, expression, frequencies])]). relacion([sujeto(['Lhx2:Emx2', double, mutants, show, opposing, effects, on, 'Olfr15', expression, that]), verbo([reveal]), complemento([independent, effects, of, these, two, transcription, factors])]). relacion([sujeto(['While', 'Lhx2', is, necessary, for, 'OR', expression, that, supports, 'OR', gene, 'choice,', 'Emx2', can]), verbo([act]), complemento(['differently;', perhaps, by, helping, to, control, the, availability, of, 'OR', genes, for, expression])]). relacion([sujeto(['CaBP4', and, 'CaBP5']), verbo([have]), complemento([been, shown, to, be, important, for, normal, visual, function])]). relacion([sujeto(['Although', 'CaBP1/caldendrin', and, 'CaBP2']), verbo([have]), complemento([been, shown, to, modulate, various, targets, in, 'vitro,', it, is, not, known, whether, they, contribute, to, the, transmission, of, light, responses, through, the, retina])]). relacion([sujeto(['We', conclude, that, 'CaBP1/caldendrin', and, 'CaBP2', are, not]), verbo([required]), complemento([for, normal, gross, retinal, and, synapse, morphology, but, are, necessary, for, the, proper, transmission, of, light, responses, through, the, 'retina;', like, other, 'CaBPs,', 'CaBP1/caldendrin', and, 'CaBP2', likely, act, by, modulating, presynaptic, 'Ca(2+)-dependent', signaling, mechanisms])]). relacion([sujeto(['Remarkable', clinical, responses]), verbo([have]), complemento([been, seen, in, patients, with, metastatic, melanoma, with, targeted, therapy, '(', 'BRAFi', 'vemurafenib,', 'MEKi)', and, with, modern, immune, 'cell-based', approaches, such, as, 'TCR', engineered, adoptive, cell, transfer, '(', 'ACT)', and, earlier, experiences, with, 'high-dose', 'IL-2'])]). relacion([sujeto(['Various', mechanisms, of, resistance, to, 'immune-mediated', apoptotic, signals]), verbo([have]), complemento([been, 'described,', including, phenotypic, 'changes,', effector, cell, 'exhaustion,', functional, 'tolerance,', deficiencies, in, 'Ag', processing, and, 'presentation,', and, mutation, or, 'down-regulation', of, antigenic, epitopes])]). relacion([sujeto(['It', is, predicted, that, these, therapies]), verbo([have]), complemento([limited, efficacy, in, patients, whose, melanomas, have, developed, resistance, to, targeted, therapy, such, as, vemurafenib])]). relacion([sujeto(['Upregulation', of, the, immune, checkpoint, molecule, 'CTLA-4', on]), verbo([activated]), complemento(['T', cells, and, its, interaction, with, 'CD80/86', blocks, 'T', cell, activation])]). relacion([sujeto(['Likewise,', the, programmed, death, receptor, 1, '(', 'PD-1)', is, another, member, of, the, 'B7:CD28', family, of, costimulatory, molecules, that]), verbo([regulates]), complemento(['T', cell, 'activation,', whose, ligand, '(', 'PD-L1)', is, expressed, on, melanomas])]). relacion([sujeto(['The', human, 'anti-PD-1', 'mAb,', 'Pembrolizumab,', overcomes, 'tolerance,']), verbo([has]), complemento([a, favorable, pharmacokinetics, profile, with, minimal, undesired, toxic, side, effects, and, has, shown, remarkable, improvement, in, melanoma, therapy])]). relacion([sujeto(['Our', aim, was, to, make, sure, that, 90, '%', of, the, patients, attending, our, heart, failure, clinics, who, were, symptomatic, and, had, an, ejection, fraction, '(', 'EF)', '≤45%', should]), verbo([have]), complemento([their, iron, studies, checked, within, the, last, six, months])]). relacion([sujeto(['In', an, effort, to]), verbo([increase]), complemento([the, proportion, of, suitable, patients, in, whom, iron, studies, are, 'requested,', we, carried, out, three, 'plan-do-study-act', '(', 'PDSA)', cycles, each, with, a, different, intervention])]). relacion([sujeto(['The', interventions]), verbo([increased]), complemento([the, number, of, suitable, patients, who, had, iron, studies, 'checked,', to, as, high, as, 100, '%', ',', however, this, effect, was, not, sustained])]). relacion([sujeto(['Root']), verbo([cause]), complemento([analysis, revealed, that, clinicians, were, unenthusiastic, to, continue, performing, iron, studies, due, to, inefficiency, in, the, process, of, admitting, patients, and, giving, them, iv, iron])]). relacion([sujeto(['We', demonstrated, that, this, service, was, feasible, and, more, efficient, as, less, time, was]), verbo([required]), complemento([waiting, for, a, bed, or, spent, in, hospital, and, was, less, costly])]). relacion([sujeto(['In', summary, we]), verbo([have]), complemento([demonstrated, interventions, which, can, increase, the, identification, of, patients, who, would, benefit, from, iv, iron, and, piloted, a, new, time, and, cost, efficient, system, of, administration, of, iv, iron])]). relacion([sujeto(['Despite', the, great, breakthroughs, we]), verbo([have]), complemento([witnessed, in, the, last, 50, years, in, the, 'prevention,', 'diagnosis,', and, treatment, of, hepatitis, 'B,', we, are, still, far, from, eradicating, or, even, curing, the, disease])]). relacion([sujeto(['Despite', the, presence, of, vast, oxidative, stress, in, hepatitis, 'B,', antioxidant, therapy, is, not, always, effective, as, a, treatment, 'strategy,', especially, considering, that, antioxidants, can]), verbo([act]), complemento([as, &, 'quot;double-edged', 'swords"', or, 'antioxidants;', if, not, used, at, the, right, time, or, place, or, in, the, right, 'combination,', these, substances, can, easily, become, 'pro-oxidants'])]). relacion([sujeto(['We', also]), verbo([suggest]), complemento([developing, an, international, platform, and, database, for, antioxidant, adjuvant, therapy, in, hepatitis, 'B', '(', 'IPAATH', and, 'IDAATH)', to, canalize, this, field, of, research, in, a, standardized, 'direction,', especially, when, complexity, is, a, problem])]). relacion([sujeto(['Key', message, &, 'quot;We', identified, both, quantitative, and, quantitative, resistance, loci, to, 'Leptosphaeria', 'maculans,', a, fungal, 'pathogen,']), verbo([causing]), complemento([blackleg, disease, in, canola])]). relacion([sujeto(['We', further, validated, statistically, significant, associations, in, four, genetic, mapping, 'populations,', demonstrating, that, 'GWAS', marker, loci, are, indeed]), verbo([associated]), complemento([with, resistance, to, 'L'])]). relacion([sujeto([&, 'quot;', 'Blackleg,']), verbo([caused]), complemento([by, 'Leptosphaeria', 'maculans,', is, a, significant, disease, which, affects, the, sustainable, production, of, canola, '(', 'Brassica', 'napus)'])]). relacion([sujeto(['This', study]), verbo([reports]), complemento([a, 'genome-wide', association, study, based, on, 18, ',', 804, polymorphic, 'SNPs', to, identify, loci, associated, with, qualitative, and, quantitative, resistance, to, 'L'])]). relacion([sujeto(['Genomic', regions, delimited, with, 694, significant, 'SNP', 'markers,', that, are]), verbo([associated]), complemento([with, resistance, evaluated, using, 12, single, spore, isolates, and, pathotypes, from, four, canola, stubble, were, identified])]). relacion([sujeto(['In', 'addition,', we, validated, statistically, significant, associations, on, 'A01,', 'A07,', and, 'A10', in, four, genetic, mapping, 'populations,', demonstrating, that, 'GWAS', marker, loci, are, indeed]), verbo([associated]), complemento([with, resistance, to, 'L'])]). relacion([sujeto(['Significantly']), verbo([associated]), complemento(['SNP', markers, provide, a, valuable, tool, to, enrich, germplasm, for, favorable, alleles, in, order, to, improve, the, level, of, resistance, to, 'L'])]). relacion([sujeto(['Ancestral', sequence, reconstruction]), verbo([has]), complemento([been, widely, used, to, test, 'evolution-based', hypotheses])]). relacion([sujeto(['Ticks', do, not, transmit, these, 'pathogens,']), verbo([suggesting]), complemento([that, these, defensins, may, act, against, a, wide, range, of, microbes, encountered, by, ticks, during, blood, feeding, or, 'off-host', periods])]). relacion([sujeto(['This', study]), verbo([suggests]), complemento([that, amino, acid, variability, and, defensin, family, expansion, increased, the, antimicrobial, spectrum, of, ancestral, tick, defensins])]). relacion([sujeto(['This', 'survey,', conducted, on, a, sample, of, the, whole, 'Taiwanese', 'population,', is, nationally, representative, and]), verbo([has]), complemento([a, high, response, rate, '(', &, 'gt;80 %)'])]). relacion([sujeto(['In', 'males,', the, prevalence, of, smoking, significantly]), verbo([decreased]), complemento(['(', rates, in, 4, surveys, were, 44.4, &, 'nbsp;%,', 44.6, &, 'nbsp;%,', 38.9, &, 'nbsp;%,', and, 34.2, &, 'nbsp;%,', 'respectively)'])]). relacion([sujeto(['Since', 2005, the, rate, of, smoking, cessation]), verbo([increased]), complemento([significantly, '(', p, =, 0.033, ')'])]). relacion([sujeto(['Early', 'anti-smoking', legislation, in, 'Taiwan', might]), verbo([have]), complemento([raised, the, awareness, of, the, harm, of, smoking])]). relacion([sujeto(['All', institutions]), verbo([have]), complemento([continuous, access, to, their, own, data, stratified, on, individual, surgeons])]). relacion([sujeto(['Registrations', are, based, on, a, 'closed,', protected, 'Internet', system]), verbo([requiring]), complemento([personal, codes, also, identifying, the, operating, institution])]). relacion([sujeto(['A', total, of, 49, 'peer-reviewed', national, and, international, publications]), verbo([have]), complemento([been, published, from, the, database, '(', 'June', 2015, ')'])]). relacion([sujeto([974, 'ASSH', members]), verbo([responded]), complemento([to, the, survey, '(', 33, '%', response, 'rate)'])]). relacion([sujeto(['Respondents', disagreed, that, the, 'ACA', would, improve, healthcare, in, the, 'United', 'States', '(', median, 2, ',', mean, 2.06, ',', scale, 1, -, 5, ')', ',', while, agreeing, that, the, 'ACA', would]), verbo([decrease]), complemento([reimbursements, specific, to, hand, surgery, '(', median, 4, ',', mean, 4.11, ')'])]). relacion([sujeto(['Magnetotactic', bacteria, produce, 'iron-rich', magnetic, nanoparticles, that, are, enclosed, by, membrane, invaginations, to, form, magnetosomes, so, they, are, able, to, sense, and]), verbo([act]), complemento([upon, 'Earth\'s', magnetic, field])]). relacion([sujeto(['Here,', we, present, the, crystal, structure, of, a, nonpolymerizing, mutant, of, 'MamK', from, 'Magnetospirillum', magneticum, 'AMB-1', at, 1.8, -, 'Å', 'resolution,']), verbo([revealed]), complemento([its, close, similarity, to, actin, and, 'MreB'])]). relacion([sujeto(['To', investigate, conformational, changes]), verbo([associated]), complemento([with, 'polymerization,', we, used, unmodified, 'MamK', protein, and, 'cryo-EM', with, helical, 3, 'D', reconstruction, in, 'RELION', to, obtain, a, density, map, and, a, fully, refined, atomic, model, of, 'MamK', in, filamentous, form, at, 3.6, -, 'Å', resolution])]). relacion([sujeto(['The', domain, movement]), verbo([causes]), complemento([several, loops, to, close, around, the, 'nucleotide-binding', pocket])]). relacion([sujeto(['The', fates, of, &, 'quot;transboundary"', environmental, systems, depend, on, how, nation, states]), verbo([interact]), complemento([with, one, another])]). relacion([sujeto(['Often,', they, implore, states, to]), verbo([act]), complemento([in, their, collective, '(', as, opposed, to, their, 'national)', interests])]). relacion([sujeto(['I', show, 'that,', as, a, general, 'matter,', states, struggle, to, cooperate, voluntarily, and, enforce, agreements, to, cooperate, but, that, they]), verbo([find]), complemento([it, relatively, easy, to, coordinate, actions])]). relacion([sujeto(['In', other, 'cases,', it]), verbo([requires]), complemento([strategic, thinking])]). relacion([sujeto(['Signal', transduction, pathways]), verbo([activated]), complemento([by, chemoattractants, have, been, extensively, 'studied,', but, little, is, known, about, the, events, mediating, responses, to, mechanical, stimuli])]). relacion([sujeto(['We', discovered, that, acute, mechanical, perturbation, of, cells]), verbo([triggered]), complemento([transient, activation, of, all, tested, components, of, the, chemotactic, signal, transduction, 'network,', as, well, as, actin, polymerization])]). relacion([sujeto(['These', results, taken, together]), verbo([suggest]), complemento([that, chemotactic, and, mechanical, stimuli, trigger, activation, of, a, common, signal, transduction, network, that, integrates, external, cues, to, regulate, cytoskeletal, activity, and, drive, cell, migration])]). relacion([sujeto(['Myocardial', endothelial, cells]), verbo([promote]), complemento([cardiomyocyte, 'hypertrophy,', possibly, through, the, release, of, growth, factors])]). relacion([sujeto(['The', identity, of, these, 'factors,', 'however,', remains, largely, 'unknown,', and, we, hypothesized, here, that, the, secreted, 'C1q-TNF-related', 'protein-9', '(', 'CTRP9)', might]), verbo([act]), complemento([as, endothelial, derived, protein, to, modulate, heart, remodeling, in, response, to, pressure, overload])]). relacion([sujeto(['CTRP9', mRNA, expression, was]), verbo([enhanced]), complemento([in, hypertrophic, human, hearts, and, in, mouse, hearts, after, transverse, aortic, constriction, '(', 'TAC)'])]). relacion([sujeto(['CTRP9', 'overexpression,', in, 'turn,']), verbo([promoted]), complemento([hypertrophic, cardiac, remodeling, and, dysfunction, after, 'TAC', in, mice, and, induced, hypertrophy, in, isolated, adult, cardiomyocytes])]). relacion([sujeto(['Mechanistically,', 'CTRP9', 'knock-out', mice, showed, strongly, reduced, levels, of]), verbo([activated]), complemento([prohypertrophic, 'ERK5', during, 'TAC', compared, to, 'wild-type', 'mice,', while, 'CTRP9', overexpression, entailed, increased, 'ERK5', activation, in, response, to, pressure, overload])]). relacion([sujeto(['Inhibition', of, 'ERK5', by, a, dominant, negative, 'MEK5', mutant, or, by, the, 'ERK5/MEK5', inhibitor, 'BIX02189', blunted, 'CTRP9']), verbo([triggered]), complemento([hypertrophy, in, isolated, adult, cardiomyocytes, in, vitro, and, attenuated, mouse, cardiomyocyte, hypertrophy, and, cardiac, dysfunction, in, 'vivo,', respectively])]). relacion([sujeto(['Downstream', of, 'ERK5,', we, identified, the, prohypertrophic, transcription, factor, 'GATA4,', which, was, directly]), verbo([activated]), complemento([through, 'ERK5', dependent, phosphorylation])]). relacion([sujeto(['The', upregulation, of, 'CTRP9', during, hypertrophic, heart, disease, facilitates, maladaptive, cardiac, remodeling, and, left, ventricular, dysfunction, and, might, constitute, a, therapeutic]), verbo([target]), complemento([in, the, future])]). relacion([sujeto(['Non-small', cell, lung, cancer, '(', 'NSCLC)', is, the]), verbo([leading]), complemento([cause, of, 'cancer-associated', deaths, worldwide])]). relacion([sujeto(['Given', the, efficacy, of, membrane, proteins, as, therapeutic]), verbo([targets]), complemento([in, human, 'malignancies,', we, examined, 'cell-surface', receptors, that, may, act, as, drivers, of, lung, tumorigenesis])]). relacion([sujeto(['Here', we]), verbo([report]), complemento([that, the, 'PROTOCADHERIN', 'PCDH7', is, overexpressed, frequently, in, 'NSCLC', tumors, where, this, event, is, associated, with, poor, clinical, outcome])]). relacion([sujeto(['PCDH7', overexpression, synergized, with, 'EGFR', and, 'KRAS', to]), verbo([induce]), complemento(['MAPK', signaling, and, tumorigenesis])]). relacion([sujeto(['Conversely,', 'PCDH7', depletion]), verbo([suppressed]), complemento(['ERK', 'activation,', sensitized, cells, to, 'MEK', inhibitors, and, reduced, tumor, growth])]). relacion([sujeto(['By', establishing, an, oncogenic, role, for, 'PCDH7', in, lung, 'tumorigenesis,', our, results]), verbo([provide]), complemento([a, rationale, to, develop, novel, 'PCDH7', targeting, therapies, which, act, at, the, cell, surface, of, 'NSCLC', cells, to, compromise, their, growth])]). relacion([sujeto(['The', school, environment]), verbo([provides]), complemento([an, ideal, context, to, deliver, prevention, 'programs,', with, potential, to, offset, the, trajectory, towards, disorder])]). relacion([sujeto(['The', aim, of, this, review, was, to]), verbo([provide]), complemento([a, comprehensive, evaluation, of, 'randomised-controlled', trials, of, psychological, 'programs,', designed, to, prevent, depression, 'and/or', anxiety, in, children, and, adolescents, delivered, in, school, settings])]). relacion([sujeto(['Subgroup', analyses]), verbo([suggested]), complemento([that, universal, depression, prevention, programs, had, smaller, effect, sizes, at, 'post-test', relative, to, targeted, programs])]). relacion([sujeto(['For', 'anxiety,', effect, sizes, were, comparable, for, universal, and]), verbo([targeted]), complemento([programs])]). relacion([sujeto(['Meta-regression', confirmed, that]), verbo([targeted]), complemento([programs, predicted, larger, effect, sizes, for, the, prevention, of, depression])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, the, refinement, of, 'school-based', prevention, programs, have, the, potential, to, reduce, mental, health, burden, and, advance, public, health, outcomes])]). relacion([sujeto(['Recent', studies]), verbo([have]), complemento([estimated, 'health,', 'cost,', and, economic, burden, relating, to, 'AMR,', with, outcomes, of, interest, ranging, from, 'drug-bug', resistance, impact, on, mortality, in, a, hospital, setting, to, total, economic, impact, of, 'AMR', on, the, global, economy])]). relacion([sujeto(['However,', recent, collation, of, this, information]), verbo([has]), complemento([been, largely, 'informal,', with, no, formal, quality, assessment, of, the, current, evidence, base, '(', e])]). relacion([sujeto(['This', review, therefore, aims, to, establish, what, perspectives, and, resulting, methodologies]), verbo([have]), complemento([been, used, in, establishing, the, burden, of, 'AMR,', whilst, also, ascertaining, the, quality, of, these, studies])]). relacion([sujeto(['This', review, will]), verbo([provide]), complemento([an, overview, of, previous, 'health,', cost, and, economic, definitions, of, burden, and, the, resultant, impact, of, these, different, definitions, on, the, burden, of, 'AMR', estimated])]). relacion([sujeto(['The', review, will, also, explore, the, methods, that]), verbo([have]), complemento([been, used, to, calculate, this, burden, and, discuss, resulting, study, quality])]). relacion([sujeto(['This', review, can, therefore]), verbo([act]), complemento([as, a, guide, to, methods, for, future, research, in, this, area])]). relacion([sujeto(['We', interviewed, stakeholders, to, identify, the, challenges]), verbo([associated]), complemento([with, the, 'ACA', 'Marketplace', health, insurance, enrollment, and, elicited, feedback, about, what, to, include, in, health, insurance, decision, support, tools])]). relacion([sujeto(['Interviews', were]), verbo([transcribed]), complemento([and, themes, were, identified, using, inductive, thematic, analysis])]). relacion([sujeto(['Stakeholders', stated, that, consumers, felt, frustrated, by, unclear, 'terminology,', high, plan, 'costs,', and, complex, calculations]), verbo([required]), complemento([to, assess, costs])]). relacion([sujeto(['Strategies', that, clarify, health, insurance, terms, using, plain, language, and, 'graphics,', acknowledge, concern]), verbo([associated]), complemento([with, making, the, wrong, 'choice,', calculate, and, enable, cost, 'comparison,', and, tailor, information, to, 'consumers\'', unique, needs, could, benefit, those, enrolling, in, 'ACA', 'Marketplace', 'plans,', 'Narratives', developed, should, be, simple, and, inclusive, enough, for, diverse, populations])]). relacion([sujeto(['Our', analysis, identified, several, functional, correlated, genes, including, chalcone, synthase, '(', 'CHS),', chlorophyll, 'a-b']), verbo([binding]), complemento([protein, '(', 'CAB)', and, other, genes, that, are, implicated, in, 'C:N', balancing, 'mechanism,', such, as, alternative, oxidase, 1, 'B', '(', 'OsAOX1B),', malate, dehydrogenase, '(', 'OsMDH)', and, lysine, and, histidine, specific, transporter, 1, '(', 'OsLHT1)'])]). relacion([sujeto(['Additionally,', six, jasmonate, synthetic, genes, and, key, regulatory, genes]), verbo([involved]), complemento([in, abiotic, and, biotic, 'stresses,', such, as, 'OsMYB4,', autoinhibited, calcium, 'ATPase', 3, '(', 'OsACA3)', and, pleiotropic, drug, resistance, 9, '(', 'OsPDR9),', were, differentially, expressed, under, high, 'C:low', 'N', treatment])]). relacion([sujeto(['Coexpression', network, analysis, of, these, genes, identified, eight, jasmonate, 'ZIM', domain, protein, '(', 'OsJAZ)', genes, and, several, defense, response, related, 'regulators,']), verbo([suggesting]), complemento([that, high, 'C:low', 'N', status, may, act, as, a, stress, 'condition,', which, induces, defense, responses, mediated, by, jasmonate, signaling, pathway])]). relacion([sujeto(['Here', we, show, that, budding, yeast, 'Rif1']), verbo([inhibits]), complemento(['DNA', replication, initiation, at, the, rDNA, locus])]). relacion([sujeto(['Absence', of, 'Rif1,', or, disruption, of, its, interaction, with, 'PP1/Glc7', 'phosphatase,']), verbo([leads]), complemento([to, more, intensive, rDNA, replication])]). relacion([sujeto(['The', effect, of, 'Rif1-Glc7', on, rDNA, replication, is, similar, to, that, of, the, 'Sir2', 'deacetylase,', and, the, two, would, appear, to]), verbo([act]), complemento([in, the, same, 'pathway,', since, the, rif1Δ, sir2Δ, double, mutant, shows, no, further, increase, in, rDNA, replication])]). relacion([sujeto(['Loss', of, 'Rif1-Glc7', activity, is, also, accompanied, by, an]), verbo([increase]), complemento([in, rDNA, repeat, instability, that, again, is, not, additive, with, the, effect, of, sir2Δ])]). relacion([sujeto(['These', data]), verbo([suggest]), complemento([that, the, repression, of, origin, activation, by, 'Rif1-Glc7', is, important, to, avoid, the, deleterious, accumulation, of, stalled, replication, forks, at, the, rDNA, 'RFB,', which, become, lethal, when, fork, stability, is, compromised])]). relacion([sujeto(['Finally,', we, show, that, 'Rif1-Glc7,', unlike, 'Sir2,']), verbo([has]), complemento([an, important, effect, on, origin, firing, outside, of, the, rDNA, locus, that, serves, to, prevent, activation, of, the, 'DNA', replication, checkpoint])]). relacion([sujeto(['Our', results, thus]), verbo([provide]), complemento([insights, into, a, mechanism, of, replication, control, within, a, large, repetitive, chromosomal, domain, and, its, importance, for, the, maintenance, of, genome, stability])]). relacion([sujeto(['These', findings, may]), verbo([have]), complemento([important, implications, for, 'metazoans,', where, large, blocks, of, repetitive, sequences, are, much, more, common])]). relacion([sujeto(['The', model, considers, six, types, of, 'strands:', the, two, functional, 'sequences,', the, complementary, strands, to, these, sequences, '(', which, are]), verbo([required]), complemento([as, 'templates),', and, 'non-functional', mutants, of, the, two, sequences, '(', which, act, as, 'parasites)'])]). relacion([sujeto(['We', show, that, coexistence, of, unlinked, polymerases, and, synthetases, is, possible, in, this, spatial, model, under, conditions, in, which, neither, sequence, could, survive, 'alone;', 'hence,', there, is, a, selective, force, for]), verbo([increasing]), complemento([complexity])]). relacion([sujeto(['The', sensitivity, of, this, 'two-ribozyme', system]), verbo([suggests]), complemento([that, evolution, of, a, system, of, many, types, of, ribozymes, would, be, difficult, in, a, purely, spatial, model, with, unlinked, genes])]). relacion([sujeto(['We', therefore, speculate, that, linkage, of, genes, onto, 'mini-chromosomes', and, encapsulation, of, strands, in, protocells, would]), verbo([have]), complemento([been, important, fairly, early, in, the, history, of, life, as, a, means, of, enabling, more, complex, systems, to, evolve])]). relacion([sujeto(['The', 2014, 'United', 'States', 'Preventive', 'Services', 'Task', 'Force', systematic, review]), verbo([found]), complemento([abdominal, aortic, aneurysm, '(', 'AAA)', screening, decreased, related, mortality, by, close, to, half])]). relacion([sujeto(['Despite', the, simplicity, of, 'screening,', research]), verbo([suggests]), complemento([poor, adherence, to, the, recommended, 'AAA', screening, guidelines])]). relacion([sujeto([2, ',']), verbo([suggesting]), complemento([patients, were, more, likely, to, be, screened, as, a, result, of, the, electronic, 'reminder,', 'OR', =, 4.73, '(', 95, '%', 'CI:', 1.77, -, 12.65, ')'])]). relacion([sujeto(['This', improvement]), verbo([translates]), complemento([to, a, large, effect, 'size,', 'Cohen\'s', d, =, 0.86, '(', 95, '%', 'CI:', 0.31, -, 1.4, ')'])]). relacion([sujeto(['Electronic', reminders, are, a, simple, 'EMR', addition, that, can]), verbo([provide]), complemento(['evidence-based', education, while, improving, adherence, rates, with, preventive, health, screening, measures])]). relacion([sujeto(['The', 'Affordable', 'Care', 'Act', established, policy, mechanisms, to]), verbo([increase]), complemento([health, insurance, coverage, in, the, 'United', 'States'])]). relacion([sujeto(['While', insurance, coverage]), verbo([has]), complemento(['increased,', 10, '%', -, 15, '%', of, the, 'US', population, remains, uninsured])]). relacion([sujeto(['A', total, of, 2742, 'US', residents, ages, 18, -, 64, ',', 525, uninsured, in, fall, 2013, ',']), verbo([participating]), complemento([in, the, 'RAND', 'American', 'Life', 'Panel,', a, nationally, representative, internet, panel])]). relacion([sujeto(['Among', the, uninsured, in, 2013, ',', higher, financial, and, health, insurance, literacy, were]), verbo([associated]), complemento([with, greater, probability, of, being, insured, in, 2015])]). relacion([sujeto(['Co-inhibitory', and, 'co-stimulatory', receptors]), verbo([act]), complemento([in, concert, to, regulate, adaptive, immune, cell, 'function,', and, the, balance, of, these, receptors, is, essential, for, the, maintenance, of, immune, homeostasis])]). relacion([sujeto(['Functional', blockade, of, the, 'co-inhibitory', receptors, such, as, cytotoxic, 'T-lymphocyte-associated', protein, 4, '(', 'CTLA-4)', and, programmed, cell, death, 1, '(', 'PD-1)']), verbo([have]), complemento([yielded, encouraging, outcomes, in, 'tumors,', generating, substantial, interest, in, seeking, for, additional, 'co-inhibitory', molecules, that, may, act, as, potential, interfering, targets])]). relacion([sujeto(['T-cell', 'Ig', and, 'ITIM', domain, '(', 'TIGIT)', is, a, newly, identified, 'co-inhibitory', receptor]), verbo([expressed]), complemento([by, regulatory, 'T', cells, '(', 'Tregs),', activated, 'T', 'cells,', and, natural, killer, '(', 'NK)', cells])]). relacion([sujeto(['Several', groups]), verbo([reported]), complemento([consistently, that, 'TIGIT', expression, was, elevated, on, 'CD8(+)', 'TILs', and, 'Tregs', in, a, variety, of, tumors])]). relacion([sujeto(['Moreover,', 'TIGIT', blockade]), verbo([has]), complemento([exhibited, therapeutic, benefits, in, animal, models, of, different, tumors])]). relacion([sujeto(['Therefore,', 'TIGIT', upregulation, plays, an, important, role, in, tumor, immunity, and, may, serve, as, a, promising, therapeutic]), verbo([target]), complemento([for, tumor, management])]). relacion([sujeto(['The', amino, acid, sequence, of, 'Dnmt2', is, very, similar, to, the, catalytic, domains, of, bacterial, and, eukaryotic, 'DNA-(cytosine', 5, ')', -, 'methyltransferases,', but, it, efficiently, catalyzes, tRNA, 'methylation,', while, its, 'DNA', methyltransferase, activity, is, the, subject, of, controversial]), verbo([reports]), complemento([with, rates, varying, between, zero, and, very, weak])]). relacion([sujeto(['By', using, composite, nucleic, acid, molecules, as, 'substrates,', we, surprisingly]), verbo([found]), complemento([that, 'DNA', 'fragments,', when, presented, as, covalent, 'DNA-RNA', hybrids, in, the, structural, context, of, a, 'tRNA,', can, be, more, efficiently, methylated, than, the, corresponding, natural, tRNA, substrate])]). relacion([sujeto(['Furthermore,', by, stepwise, development, of, 'tRNA(Asp),', we, showed, that, this, natural, 'Dnmt2', substrate, could, be, engineered, to, employ, 'RNAs', that]), verbo([act]), complemento([like, guide, 'RNAs', in, vitro])]). relacion([sujeto(['Several', problems, from, the, domain, of, 'engineering,', 'logistics,', economics, and, transportation]), verbo([have]), complemento([inherent, nested, structure, which, requires, them, to, be, modeled, as, bilevel, optimization, problems])]). relacion([sujeto(['Increasing', size, and, complexity, of, such, problems]), verbo([has]), complemento([prompted, active, theoretical, and, practical, interest, in, the, design, of, efficient, algorithms, for, bilevel, optimization])]). relacion([sujeto(['Given', the, nested, nature, of, bilevel, 'problems,', the, computational, effort, '(', number, of, function, 'evaluations)']), verbo([required]), complemento([to, solve, them, is, often, quite, high])]). relacion([sujeto(['WhileMAs']), verbo([have]), complemento([been, quite, successful, in, solving, single, level, optimization, 'problems,', there, have, been, relatively, few, studies, exploring, their, potential, for, solving, bilevel, optimization, problems])]). relacion([sujeto(['There', was, no, severe, adverse, effect]), verbo([reported]), complemento([for, either, group])]). relacion([sujeto(['CGRP', is, widely, distributed, in, the, nervous, 'system,', particularly, at, anatomical, areas, thought, to, be]), verbo([involved]), complemento([with, migraine, 'pathophysiology,', including, the, trigeminovascular, nociceptive, system])]). relacion([sujeto(['Over', the, past, two, 'decades,', a, convergence, of, basic, and, clinical, evidence]), verbo([has]), complemento([established, the, 'CGRP', as, a, key, player, in, migraine])]). relacion([sujeto(['CGRP']), verbo([enhances]), complemento([sensitivity, to, sensory, input, at, multiple, levels, in, both, the, periphery, and, central, nervous, system])]). relacion([sujeto(['Within', the, 'brain,', the, wide, distribution, of, 'CGRP', and, 'CGRP', receptors]), verbo([provides]), complemento([numerous, possible, targets, for, 'CGRP', to, act, as, a, neuromodulator])]). relacion([sujeto(['Now,', 'CGRP']), verbo([has]), complemento([emerged, as, a, promising, therapeutic, target, for, a, number, of, novel, treatments, for, migraine])]). relacion([sujeto(['GABAA', receptors, '(', 'GABAARs)']), verbo([mediate]), complemento([the, majority, of, fast, inhibitory, neurotransmission, in, the, brain, via, synergistic, association, with, the, postsynaptic, scaffolding, protein, gephyrin, and, its, interaction, partners])]). relacion([sujeto(['However,', unlike, their, counterparts, at, glutamatergic, 'synapses,', gephyrin, and, its]), verbo([binding]), complemento([partners, lack, canonical, protein, interaction, 'motifs;', 'hence,', the, molecular, basis, for, gephyrin, scaffolding, has, remained, unclear])]). relacion([sujeto(['We', demonstrate, that, crosstalk, between, 'SUMOylation,', acetylation, and, phosphorylation, pathways]), verbo([regulates]), complemento([gephyrin, scaffolding])]). relacion([sujeto(['Together,', our, results, demonstrate, that, concerted, modifications, on, a, protein, scaffold, by, evolutionarily]), verbo([conserved]), complemento([yet, functionally, diverse, signalling, pathways, facilitate, 'GABAergic', transmission])]). relacion([sujeto(['It', is, necessary, to, investigate, the]), verbo([causes]), complemento([for, these, low, immunization, rates])]). relacion([sujeto(['Scores', on, attitudes, and, knowledge]), verbo([increase]), complemento([with, the, academic, year])]). relacion([sujeto(['Attitudes']), verbo([act]), complemento([as, a, moderating, variable, between, knowledge, and, 'behaviours/behavioural', intentions])]). relacion([sujeto(['Quantitative', 'real-time', 'PCR', '(', 'qRT-PCR)']), verbo([has]), complemento([been, used, extensively, to, analyze, gene, expression, and, decipher, gene, function])]). relacion([sujeto(['The', optimal, suite, of, recommended, reference, genes, was, as, 'follows:', succinate, dehydrogenase, '(', 'SDHA)', and, 'tubulin-alpha', '(', 'TUB-α)', for, 'temperature-treated', 'larvae;', ribosomal, protein, 'L32,', 'SDHA', and, glutathione, 'S-transferase', were, best, for, all, developmental, 'stages;', 'ACT', and, 'TUB-α', for, male, and, female, 'adults;', 'SDHA', and, 'TUB-α', were, relatively, stable, and]), verbo([expressed]), complemento([in, different, 'tissues,', both, diapause, and, 'non-diapause', adults])]). relacion([sujeto(['Reference', gene, evaluation, was, validated, using, expression, of, two]), verbo([target]), complemento(['genes:', the, 'P450', 'CYP6', gene, and, the, heat, shock, protein, gene, 'Hsp70'])]). relacion([sujeto(['A', standardized, 'qRT-PCR', analysis, procedure, for, gene, functional, studies, is]), verbo([provided]), complemento([that, could, be, useful, in, studies, on, other, insect, species])]). relacion([sujeto(['According', to, the, results, which]), verbo([have]), complemento([been, 'obtained;', there, was, an, increase, in, serum, lactate, dehydrogenase, '(', 'LDH),', lipase, activities, and, cholesterol, 'level,', a, decrease, in, serum, total, 'protein,', calcium, and, alkaline, phosphatase, '(', 'ALP)', activity, in, 'Ag-intoxicated', rats])]). relacion([sujeto(['Moreover,', the, findings, showed, that, 'Ag(+)', ions, affected, antioxidant, defense, system, by]), verbo([decreasing]), complemento([superoxide, dismutase, '(', 'SOD)', activity, and, increasing, vitamin, 'E', concentration, with, a, high, level, of, malondialdehyde, '(', 'MDA)', in, brain, tissue])]). relacion([sujeto(['In', 'conclusion,', this, study, indicated, that, silver, could]), verbo([cause]), complemento([harmful, effects, in, animal, body, and, these, effects, can, be, more, toxic, in, high, concentrations, or, prolonged, time, exposure, to, this, metal])]). relacion([sujeto(['However,', selenium, and, vitamin, 'E']), verbo([act]), complemento([as, powerful, antioxidants, which, may, exercise, adverse, effect, against, the, toxicity, of, this, metal])]). relacion([sujeto(['Moreover,', 'ROS', are, not, only, a, major, determinant, of, stress, response, but, also]), verbo([act]), complemento([as, signaling, molecule, that, regulates, various, cellular, processes, including, 'plant-microbe', interaction])]). relacion([sujeto(['In', 'particular,', rhizosphere, constitutes, the, biologically, dynamic, zone, for, 'plant-microbe', interactions, which, forms, a, mutual, link]), verbo([leading]), complemento([to, reciprocal, signaling, in, both, the, partners])]). relacion([sujeto(['Among', 'plant-microbe', 'interactions,', symbiotic, associations, of, arbuscular, mycorrhizal, fungi, '(', 'AMF)', and, arbuscular, 'mycorrhizal-like', fungus, especially, 'Piriformospora', indica, with, plants, are, well, known, to, improve, plant, growth, by, alleviating, the, 'stress-impacts', and, consequently]), verbo([enhance]), complemento([the, plant, fitness])]). relacion([sujeto([indica, colonization, mainly]), verbo([enhances]), complemento(['ROS-metabolism,', maintains, 'ROS-homeostasis,', and, thereby, averts, higher, 'ROS-level', accrued, inhibition, in, plant, cellular, processes, and, plant, growth, and, survival, under, stressful, environments])]). relacion([sujeto(['This', article, summarizes, the, major, outcomes, of, the, recent]), verbo([reports]), complemento([on, the, 'ROS-generation,', scavenging, and, signaling, in, 'biotic-abiotic', stressed, plants, with, 'AMF', and, 'P'])]). relacion([sujeto(['Acute', 'graft-versus-host', disease, '(', 'GvHD)']), verbo([causes]), complemento([high, mortality, in, patients, undergoing, allogeneic, hematopoietic, cell, transplantation])]). relacion([sujeto(['An', early, event, in, the, classical, pathogenesis, of, acute, 'GvHD', is, tissue, damage]), verbo([caused]), complemento([by, the, conditioning, treatment, or, infection, that, consecutively, leads, to, translocation, of, bacterial, products, '[', 'pathogen-associated', molecular, patterns, '(', 'PAMPs)]', into, blood, or, lymphoid, 'tissue,', as, well, as, 'danger-associated', molecular, patterns, '(', 'DAMPs),', mostly, intracellular, components, that, act, as, 'pro-inflammatory', 'agents,', once, they, are, released, into, the, extracellular, space])]). relacion([sujeto(['A', subtype, of, 'DAMPs', is, 'nucleotides,', such, as, adenosine, triphosphate]), verbo([released]), complemento([from, dying, cells, that, can, activate, the, innate, and, adaptive, immune, system, by, binding, to, purinergic, receptors])]). relacion([sujeto(['Binding', to, certain, purinergic, receptors]), verbo([leads]), complemento([to, a, 'pro-inflammatory', microenvironment, and, promotes, allogeneic, 'T', cell, priming])]). relacion([sujeto(['After', 'priming,', 'T', cells, migrate, to, the, acute, 'GvHD']), verbo([target]), complemento(['organs,', mainly, 'skin,', 'liver,', and, the, gastrointestinal, tract, and, induce, cell, damage, that, further, amplifies, the, release, of, intracellular, components])]). relacion([sujeto(['The', mechanism, of, selection, on, 'host-microbe', assemblages, remains, 'contentious,', particularly, regarding, whether, selection]), verbo([acts]), complemento([differently, on, hosts, and, their, microbial, symbionts])]). relacion([sujeto(['Finally,', we]), verbo([provide]), complemento([a, mathematical, model, to, test, whether, interactions, between, hosts, and, microbes, are, necessary, to, describe, the, niche, of, either, partner])]). relacion([sujeto(['Our', synthesis, highlights, the, phenotypic, effects, of, 'host-microbe', interactions, while, respecting, the, unique, lifestyles, of, each, 'partner,', and, thereby]), verbo([provides]), complemento([a, unified, framework, to, describe, how, selection, might, act, on, a, host, that, is, associated, with, its, microbiome])]). relacion([sujeto(['Methods', 'We', analyzed, data, from, 15, ',', 763, men, and, 18, ',', 479, women, aged, 20, years, and, older, who]), verbo([participated]), complemento([in, a, 'one-day', pedometer, measurement, during, any, part, of, the, 'NHNS', between, 2006, and, 2010])]). relacion([sujeto(['Intestinal', fibrosis, is, an, intractable, complication, of, 'Crohn\'s', disease, '(', 'CD),', 'and,', when, occurring, 'excessively,']), verbo([causes]), complemento([severe, intestinal, obstruction, that, often, necessitates, surgical, resection])]). relacion([sujeto(['The', fibrosis, is, characterized, by, an, imbalance, in, the, turnover, of, extracellular, matrix, '(', 'ECM)', 'components,', where, intestinal, 'fibroblasts/myofibroblasts', play, active, roles, in, 'ECM', 'production,', fibrogenesis, and, tissue, 'remodeling,', which, eventually]), verbo([leads]), complemento([to, the, formation, of, stenotic, lesions])]). relacion([sujeto(['Recently,', we, explored, the, potential, implications, of, transient, receptor, potential, '(', 'TRP)', channels, in, the, pathogenesis, of, intestinal, 'fibrosis,', since, they, are, known, to]), verbo([act]), complemento([as, cellular, stress, 'sensors/transducers', affecting, intracellular, 'Ca(2+)', 'homeostasis/dynamics,', and, are, involved, in, a, broad, spectrum, of, cell, pathophysiology, including, inflammation, and, tissue, remodeling])]). relacion([sujeto(['We']), verbo([report]), complemento([rural, 'women\'s', access, barriers, and, the, 'PPACA', elements, that, address, these, barriers, as, well, as, potential, gaps])]). relacion([sujeto(['One', goal, of, the, 'Patient', 'Protection', and, 'Affordable', 'Care', 'Act', '(', 'ACA)', is, to]), verbo([increase]), complemento([access, to, health, care, and, health, insurance, for, the, 'country\'s', most, vulnerable, and, underserved, populations])]). relacion([sujeto(['The', authors, conclude, that, effective, transition, efforts, will]), verbo([involve]), complemento([extensive, collaboration, among, school, and, agency, 'professionals,', 'families,', and, the, young, adult, who, is, deafblind])]). relacion([sujeto(['The', neuropathology, of, 'Alzheimer\'s', disease, '(', 'AD)']), verbo([recognizes]), complemento([intraneuronal, and, extracellular, neurofibrillary, formation, responsible, for, neuronal, degeneration])]). relacion([sujeto(['The', most, relevant, pathological, findings]), verbo([reported]), complemento([in, schizophrenia, originate, from, computer, assisted, tomography, '(', 'CT),', 'Magnetic', 'Resonance', 'Imaging', '(', 'MRI)', studies, and, 'Diffusion', 'Tensor', 'Imaging', '(', 'DTI),', suggesting, the, brain, abnormalities, involved, in, the, pathophysiology, of, schizophrenia])]). relacion([sujeto(['The', theory, of, fetal, programming, illustrates, the, epigenetic, factors, that, may]), verbo([act]), complemento([during, the, intrauterine, life, on, brain, 'development,', with, relevant, consequences, on, the, susceptibility, to, develop, 'AD', or, schizophrenia, later, in, life])]). relacion([sujeto(['The', neuropathological, interpretation, of, 'AD', and, schizophrenia, shows, that, the, presence, of, severe, neuropathological, changes, is, not, always]), verbo([associated]), complemento([with, severe, cognitive, impairment])]). relacion([sujeto(['It']), verbo([has]), complemento([been, established, in, mouse, that, the, 'LIF/Jak/Stat-Nanog', axis, acts, as, a, positive, regulator, to, support, the, pluripotent, state, of, cells, whereas, 'Fgf/Erk', signaling, acts, as, a, negative, regulator, to, direct, cells, to, enter, the, differentiating, state])]). relacion([sujeto(['In', 'chicken,', although, 'Fgf/Erk', signaling, is, known, to]), verbo([act]), complemento([as, a, negative, 'regulator,', positive, regulators, remained, unknown])]). relacion([sujeto(['Jak1/Stat3', signaling, was]), verbo([activated]), complemento([specifically, at, stages, before, 'gastrulation:', 'Stat3', protein, was, localized, in, nuclei, at, blastodermal, 'stages,', but, translocated, to, cytoplasm, after, gastrulation])]). relacion([sujeto(['We', conducted, pharmacological, and, gene, transfection, analyses, in, the, 'blastoderm-derived', colony, formation, 'assay,', in, which, 'Nanog-positive', dense, colonies, represent, a, hallmark, of, the, undifferentiated, 'state,', and]), verbo([found]), complemento([that, 'Jak1/Stat3', signaling, supports, pluripotency, in, chicken, early, embryos])]). relacion([sujeto(['We', propose, that, the, molecular, mechanisms]), verbo([regulating]), complemento([pluripotency, are, conserved, at, the, signaling, network, level, between, mouse, and, 'chicken,', and, possibly, among, a, wider, range, of, species])]). relacion([sujeto(['Larvae']), verbo([respond]), complemento([to, 'near-freezing', temperatures, via, a, mutually, exclusive, set, of, singular, 'behaviors-in', 'particular,', a, 'full-body', contraction, '(', 'CT)'])]). relacion([sujeto(['Class', 'III', '(', 'CIII)', multidendritic, sensory, neurons, are, specifically]), verbo([activated]), complemento([by, cold, and, optogenetic, activation, of, these, neurons, elicits, 'CT'])]). relacion([sujeto(['Blocking', synaptic, transmission, in, 'CIII', neurons]), verbo([inhibits]), complemento(['CT'])]). relacion([sujeto(['Genetically,', the, transient, receptor, potential, '(', 'TRP)', channels, 'Trpm,', 'NompC,', and, 'Polycystic', kidney, disease, 2, '(', 'Pkd2)', are]), verbo([expressed]), complemento([in, 'CIII', 'neurons,', where, each, is, required, for, 'CT'])]). relacion([sujeto(['Misexpression', of, 'Pkd2', is, sufficient, to]), verbo([confer]), complemento([cold, responsiveness])]). relacion([sujeto(['Coactivation', of, 'cold-', and, 'heat-responsive', sensory, neurons]), verbo([suggests]), complemento([that, the, 'cold-evoked', response, circuitry, is, dominant])]). relacion([sujeto(['Here,', we, aim, to, identify, the, factors, secreted, by, velvet, that]), verbo([promote]), complemento([such, high, speed, axon, growth])]). relacion([sujeto(['Our', experiments, with, cultures, of, adult, rat, trigeminal, neurons, demonstrate, that, conditioned, medium, harvested, from, velvet, organotypic, cultures]), verbo([has]), complemento([greater, axon, 'growth-promoting', properties, than, a, medium, conditioned, by, normal, skin])]). relacion([sujeto(['The', axon, 'growth-promoting', effects, of, velvet]), verbo([act]), complemento([synergistically, with, the, extracellular, matrix, '(', 'ECM)', protein, 'laminin,', a, component, of, the, basal, lamina, present, in, the, deer, antler])]). relacion([sujeto(['A', combinatorial, approach, using, these, factors, may]), verbo([promote]), complemento([regeneration, at, high, speeds, in, patients, with, peripheral, neuropathies])]). relacion([sujeto([a, variety, of, services, to, support, women, to, undertake, weight, management, behaviours, during, pregnancy]), verbo([have]), complemento([recently, been, implemented, as, a, means, to, reduce, the, risks, to, mother, and, infant])]). relacion([sujeto(['In', the, 'UK,', midwives]), verbo([lead]), complemento([the, care, of, the, majority, of, pregnant, women, and, are, seen, as, the, ideal, source, of, referral, into, antenatal, services])]). relacion([sujeto(['However,', midwives]), verbo([have]), complemento([reported, concerns, regarding, raising, the, topic, of, weight, with, obese, women, and, negative, referral, experiences, have, been, cited, as, a, reason, not, to, engage, with, a, service])]). relacion([sujeto(['midwives\'', differing, views, on, choice, and]), verbo([gained]), complemento([agreement, to, refer, means, referral, practices, 'vary,', which, could, increase, the, risk, that, obese, women, have, inequitable, access, to, weight, management, services])]). relacion([sujeto(['However,', 'midwives\'', confidence, in, the, services, on, offer, may, be]), verbo([increased]), complemento([with, more, detailed, information, about, the, service, and, feedback, on, 'referrals,', which, would, additionally, act, as, prompts, to, refer])]). relacion([sujeto(['Training', which, demonstrates, effective, methods, of, sensitively, introducing, a, weight, management, service, to, obese, women, may]), verbo([increase]), complemento(['midwives\'', confidence, to, consistently, include, this, in, their, practice])]). relacion([sujeto(['These', measures, may, improve, 'women\'s', engagement, with, services, which]), verbo([have]), complemento([the, potential, to, reduce, the, risks, associated, with, maternal, obesity])]). relacion([sujeto(['Biologic', synthesis, of, platinum, nanoparticles, '(', 'Bio-Pt)']), verbo([has]), complemento([been, 'reported,', but, their, catalytic, activity, was, never, investigated])]). relacion([sujeto(['In', contrast, with, 'Bio-Pd,', 'Bio-Pt']), verbo([has]), complemento([a, high, catalytic, activity, in, 'PhP', 'removal,', with, 94, ',', 85, and, 70, '%', removal, of, 17, 'β-estradiol,', sulfamethoxazole, and, 'ciprofloxacin,', respectively])]). relacion([sujeto(['Bio-Pt', or, 'Bio-Pd', did, not]), verbo([act]), complemento([on, 'ibuprofen,', but, this, could, be, completely, removed, by, 'D'])]). relacion([sujeto(['This', study, demonstrates, for, the, first, time, that, 'Bio-Pt']), verbo([has]), complemento([a, high, catalytic, 'activity,', and, is, a, promising, catalyst, to, be, used, in, water, treatment, processes, for, the, removal, of, antibiotics, and, endocrine, disrupting, 'compounds,', the, most, problematic, 'PhP'])]). relacion([sujeto(['Pontine', noradrenaline]), verbo([has]), complemento([been, shown, to, increase, upon, trauma, and, associated, 'β-adrenergic', receptor, activation, appears, to, consolidate, memory, formation, of, traumatic, events])]). relacion([sujeto(['All', adult, trauma, patients, '(', '≥18', 'years)', with, 'severe,', isolated, traumatic, brain, injury, '(', intracranial, 'Abbreviated', 'Injury', 'Scale', score, '(', 'AIS)', '≥3', and, extracranial, 'AIS', &, 'lt;3)', were]), verbo([recruited]), complemento([from, the, trauma, registry, of, an, urban, university, hospital, between, 2007, and, 2011])]). relacion([sujeto(['β-blockade', appears, to]), verbo([act]), complemento([prophylactically, and, significantly, reduces, the, risk, of, 'post-traumatic', depression, in, patients, suffering, from, isolated, severe, traumatic, brain, injuries])]). relacion([sujeto(['The', literature]), verbo([reports]), complemento([a, significant, association, between, various, mental, disorders, and, 'asthma,', in, particular, depression, 'and/or', 'anxiety,', with, some, more, robust, data, regarding, anxiety, disorders])]). relacion([sujeto(['Moreover,', lifetime, and, current, anxiety, were]), verbo([associated]), complemento([with, asthma, severity, levels, '(', 'p < 0'])]). relacion([sujeto(['Current', anxiety]), verbo([increased]), complemento([the, risk, of, 'asthma,', and, that, of, an, uncontrolled, form, '(', 'p < 0'])]). relacion([sujeto(['Asthma']), verbo([increased]), complemento([the, risk, of, lifetime, anxiety, disorders, '(', 'p = 0'])]). relacion([sujeto(['Intermittent', asthma]), verbo([increased]), complemento([the, risk, of, lifetime, and, current, anxiety, disorders, '(', 'p < 0'])]). relacion([sujeto(['Anxiety', 'disorders,', in, particular, 'Lifetime', 'Anxiety', 'Disorders,', represent, the, only, psychiatric, disorder, significantly]), verbo([associated]), complemento([with, 'asthma,', with, a, possible, 'bidirectional,', 'anxiety-asthma', 'relationship,', each, of, which, can, be, caused, or, result, from, the, other])]). relacion([sujeto(['Recently,', it, was]), verbo([found]), complemento([to, act, as, a, candidate, oncogene, in, colon, 'cancer,', 'non-small-cell', lung, 'cancer,', and, gastric, cancer])]). relacion([sujeto(['Kaplan-Meier', curve, showed, that, high, expression, of, 'DIXDC1', may]), verbo([lead]), complemento([to, poor, outcome, of, glioma, patients])]). relacion([sujeto(['Serum', starvation, and, refeeding, assay, indicated, that, the, expression, of, 'DIXDC1', was]), verbo([associated]), complemento([with, cell, cycle])]). relacion([sujeto(['To', determine, whether, 'DIXDC1', could]), verbo([regulate]), complemento([the, proliferation, and, migration, of, glioma, 'cells,', we, transfected, glioma, cells, with, interfering, 'RNA-targeting', 'DIXDC1;', investigated, cell, proliferation, with, 'Cell', 'Counting', 'Kit', '(', 'CCK)-8,', flow, cytometry, 'assays,', and, colony, formation, 'analyses;', and, investigated, cell, migration, with, wound, healing, assays, and, transwell, assays])]). relacion([sujeto(['According', to, our, 'data,', knockdown, of, 'DIXDC1', significantly]), verbo([inhibited]), complemento([proliferation, and, migration, of, glioma, cells])]). relacion([sujeto(['These', data, implied, that, 'DIXDC1', might]), verbo([participate]), complemento([in, the, development, of, 'glioma,', suggesting, that, 'DIXDC1', can, become, a, potential, therapeutic, strategy, for, glioma])]). relacion([sujeto(['We', previously]), verbo([reported]), complemento([that, the, injection, of, 'nitrogen-containing', bisphosphonate, '(', 'NBP)', induced, the, site, of, erythropoiesis, to, shift, from, the, bone, marrow, '(', 'BM)', to, the, spleen])]). relacion([sujeto(['Our', previous, study, established, a, severely, anemic, mouse, model, that, was, treated, with, a, combination, of, 'NBP', with, phenylhydrazine, '(', 'PHZ),', which]), verbo([induced]), complemento([newly, discovered, hematopoietic, organs, in, the, omentum])]). relacion([sujeto(['No']), verbo([reports]), complemento([have, shown, that, new, hematopoietic, organs, form, under, any, condition])]). relacion([sujeto(['Splenectomized', mice, were, treated, with, 'NBP', to]), verbo([inhibit]), complemento([erythropoiesis, in, the, 'BM', and, then, injected, with, 'PHZ', to, induce, hemolytic, anemia])]). relacion([sujeto(['C-kit-positive', cells, were, detected, and, mRNAs, related, to, hematopoiesis, were]), verbo([expressed]), complemento([in, these, structures])]). relacion([sujeto(['The', levels, of, 'G-CSF', in, the, serum, and, hematopoietic, progenitor, cells, '(', 'HPCs)', in, the, peripheral, blood, were]), verbo([increased]), complemento([upon, treatment, with, both, 'NBP', and, 'PHZ'])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, the, induced, hematopoietic, structures, act, as, the, sites, of, erythropoiesis, and, that, 'NBP-induced', 'G-CSF', production, causes, 'HPC', 'mobilization,', homing, and, colonization, in, the, omentum, because, they, constitutively, express, some, 'factors,', including, 'SDF-1;', 'thus,', the, newly, discovered, hematopoietic, structure, in, this, study, might, be, formed])]). relacion([sujeto(['The', human, respiratory, syncytial, virus, '(', 'hRSV)', is, the, major]), verbo([cause]), complemento([of, lower, respiratory, tract, infection, in, children, and, elderly, people, worldwide])]). relacion([sujeto(['Studies', show, that, 'SH', protein]), verbo([increases]), complemento(['RSV', virulence, degree, and, permeability, to, small, 'compounds,', suggesting, it, is, involved, in, the, formation, of, ion, channels])]). relacion([sujeto(['The', combination, of, traditional, 'MD', and, 'MDeNM', was, a, very, efficient, protocol, to, investigate, functional, conformational, changes, of, transmembrane, proteins, that]), verbo([act]), complemento([as, molecular, channels])]). relacion([sujeto(['This', protocol, can, support, future, investigations, of, drug, candidates, by]), verbo([acting]), complemento([on, 'SH', protein, to, inhibit, viral, infection])]). relacion([sujeto(['Mutations', in, the, bone, morphogenetic, protein, receptor, '(', 'BMPR2)', gene]), verbo([have]), complemento([been, observed, in, 70, &, 'nbsp;%', of, patients, with, heritable, pulmonary, arterial, hypertension, '(', 'HPAH)', and, in, 11, -, 40, &, 'nbsp;%', with, idiopathic, 'PAH', '(', 'IPAH)'])]). relacion([sujeto(['However,', carriers, of, a, 'BMPR2', mutation]), verbo([have]), complemento([only, 20, &, 'nbsp;%', risk, of, developing, 'PAH'])]). relacion([sujeto(['Since', inflammatory, mediators, are]), verbo([increased]), complemento([and, predict, survival, in, 'PAH,', they, could, act, as, a, second, hit, inducing, the, development, of, pulmonary, hypertension, in, 'BMPR2', mutation, carriers])]). relacion([sujeto(['PMECs', from, 'BMPR2', mutation, carriers]), verbo([induced]), complemento([an, increase, in, 'PASMC', mitogenic, 'activity;', 'moreover,', 'endothelin-1', secretion, by, 'PMECs', from, carriers, was, higher, than, by, 'PMECs', from, 'non-carriers'])]). relacion([sujeto(['CRP']), verbo([increased]), complemento([adhesion, of, monocytes, to, 'PMECs', in, carriers, and, 'non-carriers,', and, 'TNFα', only, in, carriers])]). relacion([sujeto(['PMEC', from, 'BMPR2', mutation, carriers]), verbo([have]), complemento([enhanced, adhesiveness, for, monocytes, in, response, to, inflammatory, 'mediators,', suggesting, that, 'BMPR2', mutation, could, generate, susceptibility, to, an, inflammatory, insult, in, 'PAH'])]). relacion([sujeto(['Comorbidities']), verbo([associated]), complemento([with, obesity, have, become, a, worldwide, public, health, concern])]). relacion([sujeto(['There']), verbo([has]), complemento([been, considerable, progress, in, this, 'area,', but, research, appears, to, be, limited, to, measurements, of, levels, of, certain, parameters, in, patients, with, liver, impairment, relative, to, those, of, healthy, controls])]). relacion([sujeto(['Plasma', constituents, that]), verbo([act]), complemento([as, surrogates, of, altered, hepatic, energy, metabolism, in, response, to, food, intake, are, likely, candidates])]). relacion([sujeto(['Targeted', 'metabolomics,', combined, with, quantitation, of, the, metabolites, 'involved,']), verbo([has]), complemento([been, shown, to, be, an, efficient, measurement, tool])]). relacion([sujeto(['Indeed,', the, evaluation, of, exhaled, volatile, compounds, might, be, 'sufficient,', while, other, 'rapid,', 'sensitive,', and, reproducible, methods]), verbo([have]), complemento([been, validated, in, preliminary, studies, in, various, clinical, settings])]). relacion([sujeto(['Metabolomics', methods, are, promising, but]), verbo([require]), complemento([considerable, expertise, and, sophisticated, '(', and, 'expensive)', equipment, not, readily, available, in, all, centers])]). relacion([sujeto(['Good', outcomes, are, urgently]), verbo([required]), complemento([if, effective, prevention, programs, are, to, be, developed, to, decrease, the, prevalence, of, liver, disease])]). relacion([sujeto(['Since', this, process]), verbo([involves]), complemento([specific, 'RNA', 'molecules,', identification, of, female, cellular, material, may, be, possible, through, 'RNA', profiling])]). relacion([sujeto(['Additionally,', male, material, may, be, identified, through, 'RNAs']), verbo([expressed]), complemento([from, the, 'Y-chromosome'])]). relacion([sujeto(['RNAs', preferentially]), verbo([expressed]), complemento([in, either, sex, were, assessed, for, their, potential, to, act, as, sex, markers, in, forensic, 'RNA', assays])]). relacion([sujeto(['The', addition, of, 'sex-specific', markers, is, of, added, informative, value, in, any, 'RNA', profiling, system, and, both, markers, were, incorporated, into, existing, 'RNA', assays, that, either]), verbo([target]), complemento([body, fluids, or, organs])]). relacion([sujeto(['Cell', cycle, phase, specific, oscillation, of, gene, transcription]), verbo([has]), complemento([long, been, recognized, as, an, underlying, principle, for, ordered, processes, during, cell, proliferation])]). relacion([sujeto(['The', 'G1/S-specific', and, 'G2/M-specific', cohorts, of, genes, in, plants, are]), verbo([regulated]), complemento([by, the, 'E2F', and, the, 'MYB3R', transcription, factors])]). relacion([sujeto(['Mutant', analysis]), verbo([suggests]), complemento([that, activator, 'E2F', functions, might, not, be, fully, required, for, cell, cycle, entry])]). relacion([sujeto(['Repressor', 'MYB3Rs']), verbo([act]), complemento([outside, the, mitotic, time, window, during, cell, cycle, 'progression,', and, are, important, for, the, shutdown, of, mitotic, genes, to, impose, quiescence, in, mature, organs])]). relacion([sujeto(['In', 'plants,', there, are, multiple, such, complexes, with, distinct, compositions, and, functions, that, may, be]), verbo([involved]), complemento([in, the, coordinated, cell, cycle, and, developmental, regulation, of, 'E2F', targets, and, mitotic, genes])]). relacion([sujeto(['Epicardial', adipose, tissue, '(', 'EAT)', is, a, source, of, a, number, of, cytokines, which, could]), verbo([act]), complemento([in, the, pathogenesis, of, coronary, artery, disease, '(', 'CAD)'])]). relacion([sujeto(['The', potential, relationship, between, known, cardiovascular, risk, 'factors,', such, as, 'smoking,', dyslipidaemia, or, diabetes, mellitus, and, 'EAT', humoral, 'signalling,']), verbo([has]), complemento([not, been, fully, elucidated])]). relacion([sujeto(['No', other, clinical, variables, were]), verbo([associated]), complemento([with, cytokine, concentrations, in, a, regression, analysis])]). relacion([sujeto(['Smoking', was, independently]), verbo([associated]), complemento([with, higher, 'TNF-α', and, 'IL-6', concentrations, in, 'EAT', and, 'SAT'])]). relacion([sujeto(['A', novel, observation, that, 'pro-inflammatory', cytokines, are, elevated, in, 'EAT', in, smokers, could, contribute, to, identify, potential, mechanisms]), verbo([involved]), complemento([in, the, pathogenesis, of, adverse, effects, of, tobacco, smoking])]). relacion([sujeto(['Activators', of, soluble, guanylyl, cyclase, '(', 'sGC)']), verbo([act]), complemento([preferentially, in, conditions, of, enzyme, oxidation, or, haem, group, removal])]). relacion([sujeto(['OVA-challenge']), verbo([promoted]), complemento([marked, increases, in, eosinophil, number, in, 'BAL,', lung, 'tissue,', circulating, blood, and, bone, 'marrow,', all, of, which, were, significantly, reduced, by, 'BAY', 60, -, 2770])]). relacion([sujeto(['Increased', protein, expression, of, 'iNOS,', along, with]), verbo([decreases]), complemento([of, expression, of, sGC, '(', α1, and, β1, 'subunits)', and, cGMP, levels, were, detected, in, lung, tissue, of, 'OVA-challenged', mice])]). relacion([sujeto(['In', human, isolated, 'eosinophils,', 'BAY', 60, -, 2770, '(', 1, -, 5, &, 'nbsp;μM)', had, no, effects, on, the, cGMP, levels, and, 'eotaxin-induced', 'chemotaxis;', 'however,', prior, incubation, with, 'ODQ', '(', 10, &, 'nbsp;μM)', markedly, elevated, the, 'BAY', 60, -, 2770, -]), verbo([induced]), complemento([cyclic, 'GMP', 'production,', further, inhibiting, the, eosinophil, chemotaxis])]). relacion([sujeto(['In', human, eosinophils, under, oxidized, 'conditions,', 'BAY', 60, -, 2770, elevates, the, cGMP, levels]), verbo([causing]), complemento([cell, chemotaxis, inhibition])]). relacion([sujeto(['BAY', 60, -, 2770, may]), verbo([reveal]), complemento([a, novel, therapeutic, target, for, asthma, treatment])]). relacion([sujeto(['Complementary', nonpharmaceutical, strategies, are, needed, to]), verbo([prevent]), complemento(['and/or', ameliorate, dysregulation, of, glucose, metabolism, and, prevent, progression, from, normoglycemia, to, prediabetes, and, type, 2, diabetes, across, the, lifespan])]). relacion([sujeto(['Cocoa', 'compounds,', particularly, the, 'procyanidins,']), verbo([have]), complemento([shown, promise, for, improving, insulin, sensitivity, and, blood, glucose, homeostasis])]). relacion([sujeto(['Furthermore,', cocoa, procyanidins, exhibit, size, 'diversity,', and, evidence]), verbo([suggests]), complemento([that, procyanidin, bioactivity, and, size, may, be, related])]). relacion([sujeto(['Here,', we, show, that, a, 'procyanidin-rich', cocoa, extract, elicits, an, antidiabetic, effect, by]), verbo([stimulating]), complemento([glycogen, synthesis, and, glucose, 'uptake,', independent, of, insulin])]). relacion([sujeto(['Cocoa', procyanidins, did, not, appear, to]), verbo([act]), complemento([via, stimulation, of, 'AMPK', or, 'CaMKII', activities])]). relacion([sujeto(['These', results, demonstrate, '(', 1, ')', specific, mechanisms, by, which, cocoa, procyanidins, improve, glucose, utilization, in, skeletal, muscle, and, '(', 2, ')', that, larger, procyanidins, appear, to, possess]), verbo([enhanced]), complemento([activities])]). relacion([sujeto(['These', mechanistic, insights]), verbo([suggest]), complemento([specific, strategies, and, biological, contexts, that, may, be, exploited, to, maximize, the, antidiabetic, benefits, of, cocoa, procyanidins])]). relacion([sujeto(['Genetic', insect, 'control,', such, as, 'self-limiting', 'RIDL(2)', '(', 'Release', of, 'Insects', 'Carrying', a, 'Dominant', 'Lethal)', 'technology,', is, a, development, of, the, sterile, insect, technique, which, is, proposed, to]), verbo([suppress]), complemento([wild, populations, of, a, number, of, major, agricultural, and, public, health, insect, pests])]). relacion([sujeto(['This', is, achieved, by, mass, rearing, and]), verbo([releasing]), complemento([male, insects, that, are, homozygous, for, a, repressible, dominant, lethal, genetic, 'construct,', which, causes, death, in, progeny, when, inherited])]). relacion([sujeto(['The']), verbo([released]), complemento([genetically, engineered, '(', '\'', 'GE\')', insects, compete, for, mates, with, wild, 'individuals,', resulting, in, population, suppression])]). relacion([sujeto(['This']), verbo([found]), complemento([that, proliferation, of, resistance, is, possible, but, can, be, diluted, by, the, introgression, of, susceptible, alleles, from, the, released, 'homozygous-susceptible', 'GE', males])]). relacion([sujeto(['We', develop, this, approach, within, a, spatial, context, by, modelling, the, spread, of, a, lethal, construct, and, resistance, 'trait,', and, the, effect, on, population, 'control,', in, a, two, deme, 'metapopulation,', with, 'GE']), verbo([release]), complemento([in, one, deme])]). relacion([sujeto(['Results', show, that, spatial, effects, can, drive, an]), verbo([increased]), complemento([or, decreased, evolution, of, resistance, in, both, the, target, and, 'non-target', 'demes,', depending, on, the, effectiveness, and, associated, costs, of, the, resistant, 'trait,', and, on, the, rate, of, dispersal])]). relacion([sujeto(['A', recurrent, theme, is, the, potential, for, the, 'non-target', deme, to]), verbo([act]), complemento([as, a, source, of, resistant, or, susceptible, alleles, for, the, target, deme, through, dispersal])]). relacion([sujeto(['This', can, in, turn]), verbo([have]), complemento([a, major, impact, on, the, effectiveness, of, insect, population, control])]). relacion([sujeto(['Based', on, the, simple, thiol, compound]), verbo([mediated]), complemento(['QDs', growing, 'method,', 'CdS', 'QDs', can, be, quickly, formed, in, 'situ,', which, possess, excellent, photocatalytic, ability, for, the, oxidation, of, 3, ',', 3, '\'', ',', 5, ',', 5, '\'', -, tetramethylbenzidine, '(', 'TMB)', to, produce, a, colored, product, under, light, irradiation])]). relacion([sujeto(['Cu(2+)', can, catalyze, the, oxidation, of, sulfhydryl, groups, in, glutathione, '(', 'GSH)', which]), verbo([act]), complemento([as, a, stabilizer, for, 'CdS', 'QDs'])]). relacion([sujeto(['In', the, presence, of, 'Cu(2+),', 'GSH', is, oxidized, and]), verbo([loss]), complemento([the, stabilization, ability, for, the, growth, of, 'CdS', 'QDs,', thus, resulting, in, the, decrease, of, the, absorbance])]). relacion([sujeto(['This', sensing, system, is, 'simple,', reliable, and, holds, great, potential, to]), verbo([provide]), complemento([a, new, general, platform, for, ultrasensitive, monitoring, of, a, variety, of, analytes])]). relacion([sujeto(['Addressing', face, needs, occurs, through, conventional, and, strategic, communication, strategies, that]), verbo([respond]), complemento([to, the, emerging, needs, throughout, an, interaction])]). relacion([sujeto(['Both', parties, assess, the, 'situation,', the, 'others\'', intentions, within, the, context, of, their, own, goals, and, this, influences, how, they, choose, to]), verbo([act]), complemento([throughout, the, interaction])]). relacion([sujeto(['Face-work', 'Theory']), verbo([provides]), complemento([a, framework, to, understand, these, interaction, processes, in, 'pharmacist-patient', communication])]). relacion([sujeto(['Competence', face, needs, for, both, parties, were, the, most, dominant, need]), verbo([found]), complemento([in, negotiating, role, expectations])]). relacion([sujeto(['Linking', speech]), verbo([acts]), complemento([with, face, needs, and, threats, may, help, to, elucidate, how, 'pharmacist-patient', interactions, achieve, both, task, oriented, and, interpersonal, goals])]). relacion([sujeto(['To', assess, the, impact, of, an, accidental]), verbo([release]), complemento([of, volatilized, acrylonitrile, on, pharmacy, services, in, 'Blount', 'County,', 'Tennessee'])]). relacion([sujeto(['The', data]), verbo([suggested]), complemento([that, geographic, proximity, to, and, duration, of, the, disaster, and, the, number, of, patients, presenting, for, 72, -, hour, emergency, prescription, refills, significantly, influenced, the, overall, impact, on, pharmacy, service, delivery])]). relacion([sujeto(['The']), verbo([increase]), complemento([in, 72, -, hour, prescription, refill, requests, was, strongly, correlated, with, blood, pressure, and, diabetes, 'medications,', with, all, respondents, in, favor, of, amending, state, law, to, allow, pharmacists, to, dispense, 30, -, day, prescription, refills, in, times, of, disaster])]). relacion([sujeto(['Disasters']), verbo([have]), complemento([the, potential, to, affect, all, pharmacies, in, a, locality, but, appear, to, have, a, significant, impact, on, those, located, close, to, the, scene])]). relacion([sujeto(['These', compounds]), verbo([have]), complemento([been, reported, to, act, as, plant, growth, promoters, and, 'bio-control', agents])]). relacion([sujeto(['The', transport, channel, and, ligand]), verbo([binding]), complemento([sites, in, 'Thmfs1', are, identified, based, on, 'heuristic,', iterative, algorithm, and, structural, alignment, with, homologous, proteins])]). relacion([sujeto(['MD', simulations, were, performed, to]), verbo([reveal]), complemento([the, differential, structural, behaviour, occurring, in, the, ligand, free, and, ligand, bound, forms])]). relacion([sujeto(['We']), verbo([found]), complemento([that, two, discrete, trichothecene, binding, sites, are, located, on, either, side, of, the, central, transport, tunnel, running, from, the, cytoplasmic, side, to, the, extracellular, side, across, the, 'Thmfs1', protein])]). relacion([sujeto(['These', results, also, demonstrate, that, the, transport, of, trichodermin, occurs, via, hopping, mechanism, in, which, the, substrate, molecule, jumps, from, one]), verbo([binding]), complemento([site, to, another, lining, the, transport, tunnel])]). relacion([sujeto(['The', genus, 'Rosa', '(', 'roses)']), verbo([has]), complemento([long, been, used, in, traditional, or, folk, medicine, worldwide, for, the, treatment, of, various, types, of, arthritis, including, rheumatoid, arthritis, and, osteoarthritis])]). relacion([sujeto([',', such, as, 'flavonoids,', 'triterpenoids,', and, 'phytosterols,', could]), verbo([act]), complemento([on, different, targets, in, the, 'NF-κB', signalling, 'pathway,', inhibit, 'pro-inflammatory', enzymes, '(', e])]). relacion([sujeto(['TNF-α,', 'IL-1β,', 'IL-6,', 'CCL5),', and, reduce, oxidative, 'stress,', which, in, turn]), verbo([suppress]), complemento([inflammatory, processes])]). relacion([sujeto(['Preclinical', and, clinical, studies]), verbo([have]), complemento([demonstrated, that, these, species, possess, 'analgesic,', 'anti-arthritic,', 'anti-inflammatory,', 'anti-oxidative', and, 'bone-preserving', activities])]). relacion([sujeto(['As', a, part, of, the, 'Chemicals', 'Management', 'Plan', launched, in, 2006, ',', the, 'Government', of, 'Canada', is, assessing, and, 'managing,', where, 'appropriate,', the, potential, health, and, ecological, risks]), verbo([associated]), complemento([with, approximately, 4300, substances, under, the, 'Canadian', 'Environmental', 'Protection', 'Act', '(', 1999, ')'])]). relacion([sujeto(['Since', that, 'time,', nearly, 3000, substances]), verbo([have]), complemento([been, 'assessed,', with, human, biomonitoring, '(', 'HBM)', data, playing, an, increasingly, important, role, for, some, substances])]). relacion([sujeto([',', 'selenium,', 'triclosan,', 'phthalates),', which, highlight, the, impact, and, overall, role, 'HBM']), verbo([has]), complemento([had, in, regulatory, decision, making, in, 'Canada', for, these, three, substances, as, well, as, criteria, used, in, the, application, of, 'HBM', data, in, human, health, risk, assessment])]). relacion([sujeto(['In', addition, to, 'treatment-related', 'factors,', normal, tissue, adverse, reactions, also, manifest, from, genetic, alterations, in, distinct, pathways, majorly]), verbo([involving]), complemento(['DNA', 'damage-repair', 'genes,', inflammatory, cytokine, 'genes,', cell, cycle, 'regulation,', and, antioxidant, response])]). relacion([sujeto(['Therefore,', the, common, sequence, variants, in, these, radioresponsive, genes, might, modify, the, severity, of, normal, tissue, 'toxicity,', and, the, identification, of, the, same, could]), verbo([have]), complemento([clinical, relevance, as, a, predictive, biomarker])]). relacion([sujeto(['We', tested, 22, genetic, variants]), verbo([reported]), complemento([in, 18, genes, '(', 'ie,', 'NFE2L2,', 'OGG1,', 'NEIL3,', 'RAD17,', 'PTTG1,', 'REV3L,', 'ALAD,', 'CD44,', 'RAD9A,', 'TGFβR3,', 'MAD2L2,', 'MAP3K7,', 'MAT1A,', 'RPS6KB2,', 'ZNF830,', 'SH3GL1,', 'BAX,', and, 'XRCC1)', using, 'TaqMan', 'assay-based', 'real-time', polymerase, chain, reaction])]). relacion([sujeto(['Of', the, 22, single, nucleotide, polymorphisms, 'studied,', the, rs8193, polymorphism, lying, in, the, 'micro-RNA']), verbo([binding]), complemento([site, of, 3, '\'', -, 'UTR', of, 'CD44', was, significantly, '(', 'P='])]). relacion([sujeto([270, ')']), verbo([associated]), complemento([with, 'RT-induced', adverse, skin, reactions])]). relacion([sujeto(['Furthermore,', an]), verbo([increase]), complemento([in, the, total, number, of, risk, alleles, was, associated, with, increasing, occurrence, of, overresponses, '(', 'P='])]). relacion([sujeto(['The', genetic, polymorphisms, in, radioresponsive, genes]), verbo([act]), complemento([as, genetic, modifiers, of, acute, normal, tissue, toxicity, outcomes, after, 'RT', by, acting, individually, '(', 'rs8193),', by, 'gene-gene', interactions, '(', 'MAT1A', and, 'CD44),', 'and/or', by, the, additive, effects, of, risk, alleles])]). relacion([sujeto([1, ')', ',', but, 'multi-day', regimens, of, 'MTX']), verbo([have]), complemento([higher, historic, success, rates])]). relacion([sujeto(['Outcome', was, cost, per, 'first-line', treatment, success]), verbo([expressed]), complemento([in, terms, of, incremental, 'cost-effectiveness', ratio, '(', 'ICER)'])]). relacion([sujeto(['Small']), verbo([decreases]), complemento([in, 'QOL', dramatically, increased, the, 'ICER', during, sensitivity, analysis])]). relacion([sujeto(['While', 'Act-D', is, more, effective, for, first, line, treatment, 'success,', it, is, more, 'costly,', and, does, not]), verbo([decrease]), complemento([rate, of, 'multi-agent', chemotherapy, use])]). relacion([sujeto(['Without', an, agreed, upon, categorization, 'scheme,', 'science-based', food, safety, evaluations, and, validation, of, preventive, controls, would]), verbo([have]), complemento([to, be, completed, separately, on, each, individual, cheese, 'product,', which, is, not, feasible, considering, the, large, diversity, of, products, and, the, typically, small, scale, of, production])]). relacion([sujeto(['This', paper, proposes, and, outlines, one, such, categorization, scheme, that]), verbo([provides]), complemento([for, 30, general, categories, of, cheese])]). relacion([sujeto(['This', consensus, categorization, of, cheese]), verbo([provides]), complemento([a, foundation, for, a, feasible, approach, to, developing, 'science-based', solutions, to, assure, compliance, of, the, cheese, processors, with, food, safety, 'regulations,', such, as, those, required, by, the, 'US', 'Food', 'Safety', 'Modernization', 'Act'])]). relacion([sujeto(['The', key, purpose, of, the, cheese, categorization, proposed, here, is, to, facilitate, product, assessment, for, food, safety, risks, and]), verbo([provide]), complemento([scientifically, validated, guidance, on, effective, interventions, for, general, cheese, categories])]). relacion([sujeto(['Once', preventive, controls, for, a, given, category]), verbo([have]), complemento([been, 'defined,', these, categories, would, represent, safe, havens, for, 'cheesemakers,', which, would, allow, cheesemakers, to, safely, and, legally, produce, raw, milk, cheeses, that, meet, appropriate, 'science-based', safety, requirements, '(', e])]). relacion([sujeto(['Perinatal', regionalization, of, care]), verbo([provides]), complemento([a, broader, geographic, availability, of, obstetric, services, with, defined, levels, of, maternal, and, neonatal, care, so, that, women, can, be, transported, to, centers, with, increased, resources, and, capabilities, to, reduce, morbidity, and, mortality])]). relacion([sujeto(['The', 'Emergency', 'Medical', 'Treatment', and, 'Active', 'Labor', 'Act']), verbo([provides]), complemento([regulatory, guidance, for, care, of, laboring, women, who, require, transfer, to, a, higher, level, of, care])]). relacion([sujeto([2, -, 'Amino-2-deoxy-d-glucose', '(', 'd-glucosamine)', is, among, the, most, abundant, monosaccharides]), verbo([found]), complemento([in, natural, products])]). relacion([sujeto(['This', 'constituent,']), verbo([recognized]), complemento([for, its, 'ubiquity,', is, presented, in, most, instances, as, its, 'N-acetyl', derivative, 2, -, 'acetamido-2-deoxy-d-glucopyranose', '(', 'N-acetylglucosamine,', 'GlcNAc,', 'NAG)'])]). relacion([sujeto(['Methods', elaborated, to, investigate, these, challenges]), verbo([have]), complemento([been, intensively, 'reviewed;', 'however,', a, relatively, more, comprehensive, reviewing, of, this, subject, is, introduced, here, to, cover, some, aspects, that, have, not, been, sufficiently, covered])]). relacion([sujeto([2, -, 'Amino-2-deoxy-d-glucosylation', strategies, demand, robust, 'amino-protecting', groups, that, survive, under, a, variety, of, chemical, 'conditions,', yet]), verbo([provide]), complemento([groups, that, can, be, deprotected, under, relatively, mild, conditions])]). relacion([sujeto(['At', the, end, of, this, 'review,', a, table, that, includes, all, the, 'N-protecting', groups, that]), verbo([have]), complemento([been, used, for, glucosamine, is, provided, to, introduce, them, at, a, glance, to, aid, in, constructing, building, blocks, that, will, act, as, useful, 2, -, 'amino-2-deoxy-d-glucosyl', donors])]). relacion([sujeto(['Obesity', is, a, chronic, condition, with, significant, health, and, economic, consequences, that]), verbo([requires]), complemento([more, effective, management, in, 'Australia'])]). relacion([sujeto(['General', practitioners, '(', 'GPs)', currently]), verbo([act]), complemento([as, care, 'co-ordinators', in, line, with, national, guidelines, for, overweight, and, obesity])]). relacion([sujeto(['Not', all, patients]), verbo([have]), complemento([access, to, specialist, obesity, services, or, affordable, allied, health, care, because, of, 'location,', cost, and, 'time,', particularly, in, rural, and, remote, areas, where, there, is, a, greater, prevalence, of, obesity])]). relacion([sujeto(['GPs', will]), verbo([require]), complemento(['evidence-based', tools, to, assist, them, in, structuring, obesity, management, within, their, own, general, practice, environment])]). relacion([sujeto(['These', compounds]), verbo([have]), complemento([demonstrated, in, vitro, to, exert, 5, -, 'HT3', receptor, antagonism, which, could, benefit, 'chemotherapy-induced', nausea, and, vomiting, '(', 'CINV)'])]). relacion([sujeto(['The', site, and, mechanism, of, action, by, which, these, compounds]), verbo([interact]), complemento([with, the, 5, -, 'HT3', receptor, is, not, fully, understood, although, research, indicates, they, may, bind, to, a, currently, unidentified, allosteric, binding, site])]). relacion([sujeto(['Using', in, silico, 'techniques,', such, as, molecular, docking, and, 'GRID', 'analysis,', we]), verbo([have]), complemento([characterized, the, recently, available, murine, 5, -, 'HT3', receptor, by, identifying, sites, of, strong, interaction, with, particular, functional, groups, at, both, the, orthogonal, '(', 'serotonin)', site, and, a, proposed, allosteric, binding, site, situated, at, the, interface, between, the, transmembrane, region, and, the, extracellular, domain])]). relacion([sujeto(['Unexpectedly,', we]), verbo([found]), complemento([that, the, ginger, compounds, and, their, structural, analogs, generally, outscored, other, ligands, at, both, sites])]). relacion([sujeto(['Our', results, correlated, well, with, previous, 'site-directed', mutagenesis, studies, in, identifying, key]), verbo([binding]), complemento([site, residues])]). relacion([sujeto(['We']), verbo([have]), complemento([identified, new, residues, important, for, binding, the, ginger, compounds])]). relacion([sujeto(['Overall,', the, results]), verbo([suggest]), complemento([that, the, ginger, compounds, and, their, structural, analogues, possess, a, high, binding, affinity, to, both, sites])]). relacion([sujeto(['Notwithstanding', the, limitations, of, such, theoretical, 'analyses,', these, results]), verbo([suggest]), complemento([that, the, ginger, compounds, could, act, both, competitively, or, 'non-competitively', as, has, been, shown, for, palonosetron, and, other, modulators, of, 'CYS', loop, receptors])]). relacion([sujeto(['This', anisotropic, nature]), verbo([causes]), complemento([a, 'response,', to, an, external, 'perturbation,', along, a, small, number, of, intrinsic, 'large-amplitude', directions, as, expected, from, the, 'fluctuation-dissipation', theorem])]). relacion([sujeto(['Protein', anisotropy, can, be, exploited, for, the, calculation, of, physical, 'properties,', such, as, 'entropy,', which, can, be, employed, for]), verbo([binding]), complemento([affinity, studies])]). relacion([sujeto(['Energy', frustration, along, soft, modes, including, both, global, 'large-amplitude', and, localized, 'small-amplitude', movements, is, another, key, 'feature,', as, conformational, transitions, along, soft, 'modes,']), verbo([triggered]), complemento([by, external, perturbations, such, as, the, binding, of, other, 'molecules,', can, act, as, a, switch, to, control, function])]). relacion([sujeto(['For', 'example,', we, present, original, data]), verbo([suggesting]), complemento([that, individuals, living, in, the, 'Navajo', 'Nation', are, exposed, to, high, levels, of, uranium, in, unregulated, well, water, used, for, drinking])]). relacion([sujeto(['Inflammation', disrupts, tissue, architecture, and, 'function,', thereby, contributing, to, the, pathogenesis, of, diverse, 'diseases;', the, signals, that]), verbo([promote]), complemento([or, restrict, tissue, inflammation, thus, represent, potential, targets, for, therapeutic, intervention])]). relacion([sujeto(['Here,', we]), verbo([report]), complemento([that, genetic, or, pharmacologic, 'Hedgehog', pathway, inhibition, intensifies, colon, inflammation, '(', 'colitis)', in, mice])]). relacion([sujeto(['Within', the, 'colon,', the, 'Hedgehog', protein, signal, does, not]), verbo([act]), complemento([directly, on, the, epithelium, 'itself,', but, on, underlying, stromal, cells, to, induce, expression, of, 'IL-10,', an, 'immune-modulatory', cytokine, long, known, to, suppress, inflammatory, intestinal, damage])]). relacion([sujeto(['IL-10', function, is]), verbo([required]), complemento([for, the, full, protective, effect, of, 'small-molecule', 'Hedgehog', pathway, activation, in, 'colitis;', this, pharmacologic, augmentation, of, 'Hedgehog', pathway, activity, and, stromal, 'IL-10', expression, are, associated, with, increased, presence, of, 'CD4(+)Foxp3(+)', regulatory, 'T', cells])]). relacion([sujeto(['We', thus, identify, stromal, cells, as, cellular, coordinators, of, colon, inflammation, and]), verbo([suggest]), complemento([their, pharmacologic, manipulation, as, a, potential, means, to, treat, colitis])]). relacion([sujeto(['The', ability, to, culture, and, expand, 'B', cells, in, vitro]), verbo([has]), complemento([become, a, useful, tool, for, studying, human, immunity])]). relacion([sujeto(['This', culture, supports, extensive, 'B', cell, 'proliferation,', with, '∼10(3)-fold']), verbo([increases]), complemento([following, 8, d, in, culture, and, 10, '(', 6, ')', -, fold, increases, when, cultures, are, split, and, cultured, for, 8, more, days])]). relacion([sujeto(['Culture-derived', '(', 'CD)', 'B', cells, are, readily, cryopreserved, 'and,', when, 'recovered,']), verbo([retain]), complemento([their, ability, to, proliferate, and, differentiate])]). relacion([sujeto(['Significantly,', proliferating, 'CD', 'B', cells]), verbo([express]), complemento([high, levels, of, 'MHC', class, 'II,', 'CD80,', and, 'CD86'])]). relacion([sujeto(['CD', 'B', cells]), verbo([act]), complemento([as, 'APCs', and, present, alloantigens, and, microbial, 'Ags', to, 'T', cells])]). relacion([sujeto(['We', are, able, to]), verbo([activate]), complemento([and, expand, 'Ag-specific', memory, 'B', 'cells;', these, cultured, cells, are, highly, effective, in, presenting, 'Ag', to, 'T', cells])]). relacion([sujeto(['TCR', 'Vβ', usage, by, 'TT-activated', 'CD4(+)', 'T', cells, differs, from, resting, and, unspecifically]), verbo([activated]), complemento(['CD4(+)', 'T', cells])]). relacion([sujeto(['Moreover,', we]), verbo([found]), complemento([that, 'TT-specific', 'TCR', 'Vβ', usage, by, 'CD4(+)', 'T', cells, was, substantially, different, between, donors])]). relacion([sujeto(['This', culture, method]), verbo([provides]), complemento([a, platform, for, studying, the, 'BCR', and, 'TCR', repertoires, within, a, single, individual])]). relacion([sujeto([γδ, 'T', cells]), verbo([act]), complemento([as, a, first, line, of, defense, against, invading, pathogens])]). relacion([sujeto(['However,', 'CD8(+)', and, 'CD4(+)CD8(+)', 'Vδ1', 'T', cells, were, expanded, along, with, upregulation, of, 'NKG2D,', 'CD107,', and, granzyme, 'B,']), verbo([suggesting]), complemento([cytotoxic, function])]). relacion([sujeto(['Several', peripheral, 'Vδ1', 'and/or', 'Vδ2', 'T', cell, subpopulations]), verbo([expressing]), complemento(['IFN-γ', 'and/or', 'NKG2D', were, positively, correlated, with, decreased, plasma, viremia])]). relacion([sujeto(['Overall,', our, results]), verbo([suggest]), complemento([that, a, robust, 'Vδ1', and, 'Vδ2', 'T', cell, response, in, blood, and, the, 'FRT', of, 'SIV-infected', macaques, contribute, to, control, of, viremia])]). relacion([sujeto(['In', the, nematode, 'Caenorhabditis', 'elegans,', the, timing, of, larval, events, is]), verbo([regulated]), complemento([by, hierarchy, of, proteins, and, microRNAs, known, as, the, heterochronic, pathway])]). relacion([sujeto(['One', member, of, this, pathway, is, the, 'RNA']), verbo([binding]), complemento([protein, 'LIN-28,', which, promotes, pluripotency, and, cell, fate, decisions, in, successive, stages])]). relacion([sujeto(['Two', genetic, circuits, control, 'LIN-28', 'abundance:', it, is, negatively]), verbo([regulated]), complemento([by, the, microRNA, 'lin-4,', and, positively, regulated, by, the, transcription, factor, 'LIN-14', through, a, mechanism, that, was, previously, unknown])]). relacion([sujeto(['In', this]), verbo([report]), complemento([we, used, animals, that, lack, 'lin-4', to, elucidate, 'LIN-14\'s', activity, in, this, circuit])]). relacion([sujeto(['Furthermore,', we, show, genetically, that, these, microRNAs]), verbo([act]), complemento([between, 'lin-14', and, 'lin-28,', and, that, they, comprise, the, pathway, by, which, 'lin-14', positively, regulates, 'lin-28', 'We', also, show, that, the, 'lin-4', family, member, 'mir-237,', also, regulates, early, cell, fates])]). relacion([sujeto(['Finally,', we, show, that, the, expression, of, these, microRNAs, is, directly]), verbo([inhibited]), complemento([by, 'lin-14', 'activity,', making, them, the, first, known, targets, of, 'lin-14', that, act, in, the, heterochronic, pathway])]). relacion([sujeto(['The', pond, snail, 'Lymnaea', learns, and, remembers, not, to]), verbo([respond]), complemento([to, a, food, substance, that, is, called, conditioned, taste, aversion, '(', 'CTA)'])]). relacion([sujeto(['We', examined, this, relationship, and]), verbo([found]), complemento([the, followings])]). relacion([sujeto(['First,', snails, in, the]), verbo([act]), complemento([of, eating, just, before, the, commencement, of, training, had, the, poor, learning, and, had, the, highest, dopamine, contents, in, the, brain])]). relacion([sujeto(['That', 'is,', severe, hunger]), verbo([increased]), complemento([the, dopamine, content, in, the, brain])]). relacion([sujeto(['Bone', 'Morphogenetic', 'Proteins', '(', 'BMPs)', are, candidate, 'DTM', 'morphogens,', and, our, previous, work, demonstrated, 'BMP4', sufficiency, to]), verbo([induce]), complemento([one, 'DTM', cell, fate, -, that, of, choroid, plexus, epithelial, cells, '(', 'CPECs)', -, in, a, mouse, embryonic, stem, cell, '(', 'mESC)', culture, system])]). relacion([sujeto(['CH', and, 'CPEC', markers, were]), verbo([induced]), complemento([by, 'BMP4', in, a, 'concentration-dependent', manner, consistent, with, in, vivo, development])]). relacion([sujeto(['BMP4', concentrations, that]), verbo([led]), complemento([to, 'CH', fate, also, promoted, markers, for, 'Cajal-Retzius', 'neurons,', which, are, known, 'CH', derivatives])]). relacion([sujeto(['BMP4', concentrations, that, yielded, 'CH-', or, 'CPEC-enriched', populations, also, had, different, 'steady-state', levels, of, 'phospho-SMAD1/5/8,']), verbo([suggesting]), complemento([that, differences, in, 'BMP', signaling, intensity, underlie, 'DTM', fate, choice])]). relacion([sujeto(['These', data, indicate, that, 'BMP4', can]), verbo([act]), complemento([as, a, classic, morphogen, to, orchestrate, both, spatial, and, temporal, aspects, of, 'DTM', fate, 'acquisition,', and, can, do, so, in, the, absence, of, 'Lhx2'])]). relacion([sujeto(['Tripartite', motif, 16, '(', 'TRIM16),']), verbo([has]), complemento([been, demonstrated, to, act, as, a, tumor, suppressor, through, affecting, cell, proliferation, and, migration, or, tumorigenicity, in, carcigenesis])]). relacion([sujeto(['In', response, to, different, 'stimuli,', including, infection, with, 'Singapore', grouper, iridovirus, '(', 'SGIV)', or, 'red-spotted', grouper, nervous, necrosis, '(', 'RGNNV),', and, transfection, with, 'b-DNA', or, poly, 'I:C,', the, transcript, of, 'EcTRIM16L', were, differently]), verbo([regulated]), complemento([in, grouper, spleen, cells])]). relacion([sujeto(['After', incubation, with, 'SGIV,', the, ectopic, expression, of, 'EcTRIM16L', significantly]), verbo([enhanced]), complemento([the, viral, 'replication,', demonstrated, by, the, increase, of, cytopathic, effect, '(', 'CPE)', severity, and, viral, gene, transcriptions])]). relacion([sujeto(['Simultaneously,', we, also]), verbo([found]), complemento([that, overexpression, of, 'EcTIRM16L', 'in vitro', significantly, weakened, the, expression, of, interferon, related, 'molecules,', including, interferon, regulatory, factor, 3, '(', 'IRF3),', 'IRF7,', and, melanoma, 'differentiation-associated', protein, 5, '(', 'MDA5)'])]). relacion([sujeto(['Moreover,', the, ectopic, expression, of, 'EcTRIM16L', significantly]), verbo([decreased]), complemento([both, 'MDA5-and', mediator, of, 'IRF3', activation, '(', 'MITA)-induced', interferon, immune, responses])]). relacion([sujeto(['Prolactin-like', protein, '(', 'PRL-L;', 'LOC417800)', is, a, homolog, of, 'PRL', in, 'non-mammalian', vertebrates, and, can]), verbo([act]), complemento([as, a, functional, ligand, of, 'PRL', receptor, '(', 'PRLR)'])]). relacion([sujeto(['In', cultured, undifferentiated, granulosa, 'cells,', levels, of, 'PRL-L', transcript, were]), verbo([increased]), complemento(['(', 'P<0'])]). relacion([sujeto([5, ')', by, follicle]), verbo([stimulating]), complemento([hormone, '(', 'FSH)', treatment, while, were, not, altered, by, the, addition, of, luteinizing, hormone, '(', 'LH)'])]). relacion([sujeto(['In', 'addition,', 10, 'ng/ml', 'non-glycosylated', '(', 'NG-)', and, 1, 'ng/ml', glycosylated, '(', 'G-)', 'PRL']), verbo([increased]), complemento(['(', 'P<0'])]). relacion([sujeto(['Furthermore,', 100, 'ng/ml', 'NG-PRL']), verbo([enhanced]), complemento(['(', 'P<0'])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, 'PRL-L', mRNA, is, differentially, expressed, in, the, follicular, hierarchy, and, its, high, abundance, in, undifferentiated, granulosa, cells, is, under, the, regulation, of, 'FSH', or, 'PRL', variants, independently, or, in, combination])]). relacion([sujeto(['Moreover,', in, undifferentiated, granulosa, cells, we, also]), verbo([provide]), complemento([evidence, for, a, positive, role, for, 'PKA,', 'PKC', and, 'PI3K', signaling, while, a, negative, role, for, 'ERK2', in, mediating, 'FSH', stimulation, of, 'PRL-L', transcription])]). relacion([sujeto(['During', the, vegetative, phase, 'transition,', which, accompanies, a, reduction, of, miR156, and, a, concomitant, elevation, of, its, 'targets,', plants, acquire, reproductive, competence, such, that, 'LD', signals]), verbo([promote]), complemento([flowering])]). relacion([sujeto(['However,', it, remains, largely, unknown, how, developmental, signals, are]), verbo([associated]), complemento([with, photoperiodic, flowering])]). relacion([sujeto(['SPL3/4/5', can, directly]), verbo([bind]), complemento([to, the, promoters, of, 'APETALA1,', 'LEAFY,', and, 'FRUITFULL,', thus, mediating, their, activation, by, the, 'FT-FD', complex])]). relacion([sujeto(['Our', findings, demonstrate, that, 'SPL3/4/5']), verbo([act]), complemento([synergistically, with, the, 'FT-FD', module, to, induce, flowering, under, 'LDs,', providing, a, 'long-sought', molecular, knob, that, links, developmental, aging, and, photoperiodic, flowering])]). relacion([sujeto(['Enzymatically,', this, process, can, be, achieved, by, phenolic, acid, decarboxylases, '(', 'PADs),', which, are, able, to]), verbo([act]), complemento([on, phenolic, acid, substrates, such, as, ferulic, and, 'p-coumaric', acid])]). relacion([sujeto(['Although', many, microbial, 'PADs']), verbo([have]), complemento([been, 'characterized,', little, is, known, regarding, their, plant, homologs])]). relacion([sujeto(['Transcriptome', sequencing, in, the, liverworts]), verbo([has]), complemento([identified, seven, putative, 'PADs,', which, share, a, measure, of, sequence, identity, with, microbial, 'PADs,', but, are, typically, much, longer, proteins])]). relacion([sujeto(['The', 1197, &, 'nbsp;nt', 'CjPAD', cDNA, sequence, was, predicted, to, be]), verbo([translated]), complemento([into, a, 398, residue, protein])]). relacion([sujeto(['When', the, gene, was, heterologously]), verbo([expressed]), complemento([in, 'Escherichia', 'coli,', its, product, exhibited, a, high, level, of, 'PAD', activity, when, provided, with, either, 'p-coumaric', or, ferulic, acid, as, 'substrate,', along, with, the, conversion, of, caffeic, acid, and, sinapic, acid, to, their, corresponding, decarboxylated, products])]). relacion([sujeto(['The', transient, expression, in, tobacco, of, a, 'GFP/CjPAD', fusion, gene, demonstrated, that, the, 'CjPAD', protein, is]), verbo([expressed]), complemento([in, the, cytoplasm])]). relacion([sujeto(['It', is, first, time, a, 'PAD', was, characterized, from, plants, and, the, present, investigation]), verbo([provided]), complemento([a, candidate, gene, for, catalyzing, the, formation, of, volatile, phenols])]). relacion([sujeto(['Carybdea', marsupialis, is, a, widely, distributed, box, jellyfish]), verbo([found]), complemento([in, the, 'Mediterranean', and, in, the, tropical, waters, of, the, 'Caribbean', 'Sea'])]). relacion([sujeto(['No', further, purification, step, could, be, carried, out, due, to, the]), verbo([loss]), complemento([of, neurotoxic, activity])]). relacion([sujeto(['The', 'Fractogel', 'EMD', 'SO3(-)', fraction, was, analyzed, electrophysiologically, using, the, 'voltage-clamp', technique, in, 'Xenopus', laevis, oocytes]), verbo([expressing]), complemento([membrane, proteins, from, rat, brain, through, mRNA, injection])]). relacion([sujeto(['The', crude, venom, and, a, fraction, were, observed, to, affect, crustaceans, and, showed, at, least, two, types, of, bioactivity, in, oocytes]), verbo([expressing]), complemento([brain, proteins])]). relacion([sujeto(['These', results, evidence, the, presence, of, neurotoxins, in, 'Carybdea', marsupialis, venom, that]), verbo([act]), complemento([on, membrane, proteins, of, the, vertebrate, nervous, system])]). relacion([sujeto(['The', voluntary, use, and, abuse, of, alcohol, and, inhalants, is, a]), verbo([recognized]), complemento([health, problem, throughout, the, world])]). relacion([sujeto(['Previous', studies]), verbo([have]), complemento([shown, that, these, agents, affect, brain, function, in, a, variety, of, ways, including, direct, inhibition, of, key, ion, channels, that, regulate, neuronal, excitability])]). relacion([sujeto(['Previous', studies, from, this, laboratory, and, others]), verbo([have]), complemento([identified, key, residues, within, transmembrane, '(', 'TM)', domains, of, the, 'NMDA', receptor, that, appear, to, regulate, its, sensitivity, to, alcohol, and, anesthetics])]). relacion([sujeto(['In', this, 'study,', we, extend, these, findings, and, examine, the, role, of, a, 'TM4', residue, in]), verbo([modulating]), complemento([sensitivity, of, recombinant, 'NMDA', receptors, to, ethanol, and, toluene])]). relacion([sujeto(['Both', ethanol, '(', 100, &, 'nbsp;mM)', and, toluene, '(', 1, or, 3, &, 'nbsp;mM)', reversibly]), verbo([inhibited]), complemento(['glutamate-activated', currents, from, 'wild-type', 'NMDARs', with, 'GluN2B', containing, receptors, showing, heightened, sensitivity, to, either, agent])]). relacion([sujeto(['In', 'contrast,', toluene, inhibition, of, 'glutamate-activated', currents, in, cells]), verbo([expressing]), complemento([the, 'TM4-W', mutants, was, not, different, from, that, of, the, 'wild-type', controls])]). relacion([sujeto(['These', data]), verbo([suggest]), complemento([that, despite, similarities, in, their, action, on, 'NMDARs,', ethanol, and, toluene, may, act, at, different, sites, to, reduce, ion, flux, through, 'NMDA', receptors])]). relacion([sujeto(['It', is, unclear, if, 5, ',', 0, units, are, sufficient, to, achieve, a, therapeutic, first]), verbo([activated]), complemento([clotting, time, '(', 'ACT)'])]). relacion([sujeto(['Furthermore,', 44.6, '%', of, patients, who, achieved, the, 'American', 'College', of, 'Cardiology', 'Foundation/American', 'Heart', 'Association']), verbo([target]), complemento(['weight-based', dosing, had, an, infratherapeutic, 'ACT'])]). relacion([sujeto(['In', 'conclusion,', over, half, of, patients, with, 'ST-elevation', myocardial, infarction, administered, 5, ',', 0, units, of, 'UFH']), verbo([have]), complemento([an, infratherapeutic, first, 'ACT', and, the, high, rate, of, poor, 'TIMI', grade, flow, in, patients, with, an, infratherapeutic, 'ACT', is, concerning])]). relacion([sujeto(['A', global, subsidy, on, 'artemisinin-based', combination, therapy, '(', 'ACT)']), verbo([has]), complemento([recently, been, suggested, to, increase, access, to, the, most, effective, malaria, treatment])]). relacion([sujeto(['Assuming', that, the, individual]), verbo([has]), complemento([certain, beliefs, of, the, accuracy, of, the, 'RDT', and, the, probability, that, the, fever, is, 'malaria,', the, model, predicts, the, 'diagnosis-treatment', behaviour, of, the, individual])]). relacion([sujeto(['Solving', the, model, numerically]), verbo([suggests]), complemento([that, a, combined, subsidy, on, both, 'RDT', and, 'ACT', is, cost, minimizing, and, improves, 'diagnosis-treatment', behaviour, of, individuals])]). relacion([sujeto(['A', combined, subsidy, on, both, 'RDT', and, 'ACT', rather, than, a, single, subsidy, is, likely]), verbo([required]), complemento([to, improve, 'diagnosis-treatment', behaviour, among, individuals, seeking, care, for, malaria, in, the, private, sector])]). relacion([sujeto(['The', 'waist-worn', tracker]), verbo([provided]), complemento(['real-time', feedback, and, prompts, on, sitting, and, posture])]). relacion([sujeto(['Organisational-support', strategies, with, or, without, an, activity, tracker, resulted, in, improvements, in, 'sitting,', prolonged, sitting, and, 'standing;', adding, a, tracker]), verbo([enhanced]), complemento([stepping, changes])]). relacion([sujeto(['Improvements', were, most, evident, at, 12, &, 'nbsp;months,']), verbo([suggesting]), complemento([the, 'organisational-support', strategies, may, have, taken, time, to, embed, within, the, organisation])]). relacion([sujeto(['The', importance, of, the, 'Wnt', signaling, cascade, in, the, fields, of, developmental, 'biology,', regenerative, 'medicine,', cancer, 'genetics,', and, neurobiology]), verbo([has]), complemento([fueled, a, wide, search, for, potent, pharmacological, agents, capable, of, controlling, 'Wnt', signaling])]). relacion([sujeto(['Numerous', fields, of, study]), verbo([have]), complemento([lent, assistance, to, this, 'endeavor,', yielding, both, natural, and, synthetic, compounds, that, are, capable, of, inducing, or, inhibiting, 'Wnt', at, multiple, stages, within, the, pathway])]). relacion([sujeto(['Further,', there, is, a, large, of, body, research, which]), verbo([has]), complemento([investigated, endogenous, 'Wnt', inducers, and, 'inhibitors,', namely, the, secreted, 'Wnts,', 'Dickkof', 'proteins,', secreted, 'Frizzled-Related', 'Proteins,', and, 'Wnt', 'Inhibitory', 'Factor-1,', along, with, others, which, may, act, via, indirect, means, to, stimulate, or, inhibit, 'Wnt', '(', e])]). relacion([sujeto(['This', review, will, summarize, the, research, surrounding, currently, available, small, molecules, used, to]), verbo([target]), complemento(['Wnt', signaling])]). relacion([sujeto(['These', compounds, will, be, classified, based, upon, their, ability, to]), verbo([stimulate]), complemento([or, inhibit, 'Wnt,', their, derivation, '(', natural, or, 'synthetic),', and, their, specific, mechanism, of, action])]). relacion([sujeto(['MYB', transcription, factors, play, key, roles, in, various, 'physiological,', biochemical, and, molecular, 'responses,', which, can, both, positively, and, negatively]), verbo([regulate]), complemento([the, stress, tolerance, of, plants])]). relacion([sujeto(['In', this, 'study,', we]), verbo([report]), complemento([that, the, expression, of, 'FtMYB10,', a, 'R2R3-MYB', gene, from, 'Tartary', 'buckwheat,', was, induced, significantly, by, 'ABA', and, drought, treatments])]). relacion([sujeto(['Further', studies, showed, that, the, proline, contents, in, the, transgenic, plants, are, markedly]), verbo([decreased]), complemento([associated, with, reduced, expression, of, the, 'P5CS1', gene, under, both, normal, and, stress, conditions])]). relacion([sujeto(['Furthermore,', the, expression, of, some, 'stress-responsive', 'genes,', including, 'DREB1/CBFs,', 'RD29B,', 'RD22,', and, several, genes, of, the, 'DRE/CRT', 'class,']), verbo([decreased]), complemento([in, response, to, 'FtMYB10', overexpression, in, 'Arabidopsis'])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, 'FtMYB10', may, play, a, key, role, in, 'ABA', signaling, feedback, regulation, and, act, as, a, novel, negative, regulator, of, salt, and, drought, stress, tolerance, in, plants])]). relacion([sujeto(['The', prevalence, of, obesity, is]), verbo([increasing]), complemento([worldwide, and, has, tripled, in, men, of, reproductive, age, since, the, 1970, s])]). relacion([sujeto(['Concerningly,', obesity, is, not, only, comorbid, with, other, chronic, 'diseases,', but, there, is, mounting, evidence, that, it]), verbo([increases]), complemento([the, 'non-communicable', disease, load, in, their, children, '(', eg, 'mortality,', 'obesity,', 'autism)'])]). relacion([sujeto(['Animal', studies]), verbo([have]), complemento([demonstrated, that, paternal, obesity, increases, the, risk, of, metabolic, '(', eg, glucose, metabolism, 'defects,', 'obesity)', and, reproductive, disorders, in, offspring])]). relacion([sujeto(['Epigenetic', changes, within, sperm, are, clear, mechanistic, candidates, that, are]), verbo([associated]), complemento([with, both, changes, to, the, 'father\'s', environment, and, offspring, phenotype])]). relacion([sujeto(['Specifically', there, is, emerging, evidence, that, a, 'father\'s', sperm, microRNA, content, both]), verbo([responds]), complemento([to, paternal, environmental, cues, and, alters, the, gene, expression, profile, and, subsequent, development, of, the, early, embryo])]). relacion([sujeto(['We', used, a, mouse, model, of, high, fat, diet, '(', 'HFD)']), verbo([induced]), complemento([obesity, to, investigate, whether, male, obesity, could, modulate, sperm, microRNA, content])]). relacion([sujeto(['We', also, investigated, whether, this, alteration, to, a, 'father\'s', sperm, microRNA, content]), verbo([lead]), complemento([to, a, similar, change, in, the, sperm, of, male, offspring])]). relacion([sujeto(['This', was, presumably, due, to, the, variation, seen, within, both, groups, of, offspring, and]), verbo([suggests]), complemento([other, mechanisms, might, act, between, offspring, and, 'grand-offspring'])]). relacion([sujeto(['Thus', 13, sperm, borne, microRNAs, are]), verbo([modulated]), complemento([by, a, 'father\'s', 'HFD', and, the, presumed, transfer, of, this, altered, microRNA, payload, to, the, embryo, at, fertilisation, potentially, acts, to, alter, the, embryonic, molecular, makeup, 'post-fertilisation,', altering, its, growth, 'trajectory,', ultimately, affecting, adult, offspring, phenotype, and, may, contribute, to, paternal, programming])]). relacion([sujeto(['Complement', factor, 'H-related', protein, 1, '(', 'CFHR1)', is, a, complement, regulator, which]), verbo([has]), complemento([been, reported, to, regulate, complement, by, blocking, 'C5', convertase, activity, and, interfering, with, 'C5b', surface, association])]). relacion([sujeto(['CFHR1', also, competes, with, complement, factor, 'H', '(', 'CFH)', for]), verbo([binding]), complemento([to, 'C3b,', and, may, act, as, an, antagonist, of, 'CFH-directed', regulation, on, cell, surfaces])]). relacion([sujeto(['We']), verbo([have]), complemento([employed, 'site-directed', mutagenesis, in, conjunction, with, 'ELISA-based', and, functional, assays, to, isolate, the, binding, interaction, that, 'CFHR1', undertakes, with, complement, components, 'C3b', and, 'C3d', to, a, single, shared, interface])]). relacion([sujeto(['Moreover,', we]), verbo([have]), complemento([been, able, to, corroborate, that, dimerization, of, 'CFHR1', is, necessary, for, this, molecule, to, bind, effectively, to, 'C3b', and, 'C3d,', or, compete, with, 'CFH'])]). relacion([sujeto(['Finally,', we]), verbo([have]), complemento([established, that, 'CFHR1', competes, with, complement, factor, 'H-like', protein, 1, '(', 'CFHL-1)', for, binding, to, 'C3b'])]). relacion([sujeto(['CFHR1,', 'therefore,', not, only, competes, with, the, 'C-terminus', of, 'CFH', for]), verbo([binding]), complemento([to, 'C3b,', but, also, sterically, blocks, the, interaction, that, the, 'N-terminus', of, 'CFH', undertakes, with, 'C3b,', and, which, is, required, for, 'CFH-regulation'])]). relacion([sujeto([microRNAs, '(', 'miRNAs)', plays, an, important, role, in, tumor, development, and, progression, and]), verbo([act]), complemento([as, oncogenes, or, tumor, suppressor, genes, in, the, carcinogenesis, process])]). relacion([sujeto([miRNA, is, stable, in, 'serum,', and, recent, studies]), verbo([have]), complemento([demonstrated, the, feasibility, of, using, circulating, miRNA, as, biomarkers, in, cancer, patients])]). relacion([sujeto(['However,', 'currently,', no, serum, biomarkers, for, the, early, diagnosis, and, prognosis, of, renal, cell, carcinoma, '(', 'RCC)']), verbo([have]), complemento([been, reported])]). relacion([sujeto([30, 'cancer-free', blood, donor, volunteers, with, no, history, of, any, cancer, were]), verbo([recruited]), complemento([from, the, same, institute])]). relacion([sujeto(['The', expression, level, of, 'miR-21', and, 'miR-106', a, in, 'RCC', patients]), verbo([increased]), complemento(['significantly,', while, 'miR-21', and, 'miR-106a', decreased, after, surgery])]). relacion([sujeto(['This', outcome]), verbo([suggests]), complemento([that, serum, 'miR-21', and, 'miR-106a', expression, level, was, closely, related, with, kidney, cancer, tissue])]). relacion([sujeto(['The', 'DTI', technique, can]), verbo([act]), complemento([as, an, important, supplement, to, the, conventional, 'MRI', technique, for, 'CSC', observation])]). relacion([sujeto(['The', regulatory, framework, and, the, technical, requirements, of, the, 'US', biosimilars, program]), verbo([involve]), complemento([a, stepwise, approach, that, relies, heavily, on, analytical, methods, to, demonstrate, through, a, &, 'quot;totality', of, the, 'evidence"', that, a, proposed, product, is, biosimilar, to, its, reference, product])]). relacion([sujeto(['By', integrating, 'analytical,', 'pharmacological,', and, clinical, 'data,', each, of, which]), verbo([has]), complemento(['limitations,', a, high, level, of, confidence, can, be, reached, regarding, clinical, performance])]). relacion([sujeto(['Although', questions, and, concerns, about, the, biosimilars, pathway, remain, and, may, slow, 'uptake,', a, robust, scientific, program]), verbo([has]), complemento([been, put, in, place])]). relacion([sujeto(['When', administered, in, mixtures, it, can]), verbo([enhance]), complemento([the, quality, of, plant, 'proteins,', but, it, is, often, scarce, in, 'low-income', 'communities,', especially, in, young, 'children,', the, 'elderly,', and, pregnant, and, lactating, 'women,', who, have, increased, requirements, and, in, whom, 'high-quality', protein, also, stimulates, bone, growth, and, maintenance])]). relacion([sujeto(['Although', high, protein, intake, was]), verbo([associated]), complemento([with, increased, type, 2, diabetes, mellitus, 'risk,', milk, and, seafood, are, good, sources, of, branched, chain, amino, acids, and, 'taurine,', which, act, beneficially, on, glucose, metabolism, and, blood, pressure])]). relacion([sujeto(['However,', high, consumption, of, 'protein-rich', animal, food, is, also]), verbo([associated]), complemento([with, adverse, health, effects, and, higher, risk, for, noncommunicable, 'diseases,', partly, related, to, other, components, of, these, 'foods,', like, saturated, fatty, acids, and, potential, carcinogens, in, processed, meat, but, also, the, atherogenic, methionine, metabolite, homocysteine])]). relacion([sujeto(['The', weekly, learning, goals, program, was, developed, and, implemented, as, part, of, a]), verbo([required]), complemento([3, 'rd-year', neurology, clerkship])]). relacion([sujeto(['Eighty-six', percent]), verbo([reported]), complemento([that, the, weekly, learning, goals, increased, their, awareness, of, their, thoughts, and, actions])]). relacion([sujeto(['Seventy-eight', percent]), verbo([reported]), complemento([that, the, learning, goals, helped, to, improve, their, clinical, performance, to, some, 'degree,', and, 57, '%', reported, that, the, learning, goals, increased, their, focus, on, patient, care])]). relacion([sujeto(['For', most, 'students,', the, frequency, of, the, goals, allowed, for, close, 'self-monitoring,', and, the]), verbo([act]), complemento([of, sharing, goals, with, the, team, opened, a, new, avenue, for, dialogue, between, students, and, their, supervisors])]). relacion([sujeto(['To', investigate, whether, selective, constraints, could]), verbo([act]), complemento([on, viral, genomic, 'RNA,', synonymous, and, 'non-synonymous', substitution, rates, and, their, ratio, were, analyzed])]). relacion([sujeto(['Averages', of, all, pairwise, comparisons, obtained, in, the, 5, '\'', 'NTR-P1', region, allowed, more, synonymous, 'changes,']), verbo([suggesting]), complemento([selective, constraint, acting, in, this, region])]). relacion([sujeto(['Selective', neutrality, test, was, significantly, 'negative,']), verbo([suggesting]), complemento([a, rapid, expansion, of, 'PVY', isolates])]). relacion([sujeto(['Genetic', haplotype, network, topology]), verbo([provided]), complemento([evidence, of, the, existence, of, a, distinct, geographical, structure])]). relacion([sujeto(['This', is, the, first]), verbo([report]), complemento([of, such, genetic, analyses, conducted, on, 'PVY', isolates, from, 'Tunisia'])]). relacion([sujeto(['The', translationally, controlled, tumor, protein, '(', 'TCTP)', is, upregulated, in, a, range, of, cancer, cell, 'types,', in, 'part,', by, the, activation, of, the, mechanistic]), verbo([target]), complemento([of, rapamycin, '(', 'mTOR)'])]). relacion([sujeto(['Recently,', 'TCTP']), verbo([has]), complemento([also, been, proposed, to, act, as, an, indirect, activator, of, mTOR])]). relacion([sujeto(['Furthermore,', the]), verbo([increase]), complemento([in, 'TCTP', observed, in, the, hypertrophic, and, atrophic, conditions, 'occurred,', in, 'part,', via, a, 'rapamycin-sensitive', 'mTOR-dependent', mechanism])]). relacion([sujeto(['However,', the, overexpression, of, 'TCTP', was, not, sufficient, to]), verbo([activate]), complemento([mTOR, signaling, '(', or, increase, protein, 'synthesis)', and, is, thus, unlikely, to, take, part, in, a, recently, proposed, positive, feedback, loop, with, mTOR])]). relacion([sujeto(['Nonetheless,', 'TCTP', overexpression, was, sufficient, to]), verbo([induce]), complemento([muscle, fiber, hypertrophy])]). relacion([sujeto(['Finally,', 'TCTP', overexpression]), verbo([inhibited]), complemento([the, promoter, activity, of, the, 'muscle-specific', ubiquitin, proteasome, 'E3-ligase,', 'MuRF1,', suggesting, that, 'TCTP', may, play, a, role, in, inhibiting, protein, degradation])]). relacion([sujeto(['These', findings]), verbo([provide]), complemento([novel, data, on, the, role, and, regulation, of, 'TCTP', in, skeletal, muscle, in, vivo])]). relacion([sujeto(['In', recent, 'work,', we, demonstrated, that, it, is, possible, to, obtain, approximate, representations, of, 'high-dimensional', free, energy, surfaces, with, variationally]), verbo([enhanced]), complemento([sampling, '(', 'Shaffer,', 'P'])]). relacion([sujeto(['In', this, 'way,', it, is, possible, to, build, hierarchical, free, energy, 'surfaces,', which, are, composed, of, terms, that]), verbo([act]), complemento([on, different, length, scales])]). relacion([sujeto(['The', approach, described, in, this, paper, is, ideally, suited, for, problems, in, which, the, free, energy, surface]), verbo([has]), complemento([important, features, on, different, length, scales, or, in, which, there, is, some, natural, hierarchy])]). relacion([sujeto(['The', majority, of, cases, are]), verbo([caused]), complemento([by, autosomal, dominant, pathogenic, variants, in, the, 'COL1A1', and, 'COL1A2', genes, that, encode, type, 'I', 'collagen,', the, major, component, of, the, bone, matrix])]). relacion([sujeto(['The', remaining, cases, are]), verbo([caused]), complemento([by, autosomal, recessively, or, dominantly, inherited, mutations, in, genes, that, are, involved, in, the, 'post-translational', modification, of, type, 'I', 'collagen,', act, as, type, 'I', collagen, 'chaperones,', or, are, members, of, the, signaling, pathways, that, regulate, bone, homeostasis])]). relacion([sujeto(['The', main, goals, of, treatment, in, 'OI', are, to]), verbo([decrease]), complemento([fracture, 'incidence,', relieve, bone, 'pain,', and, promote, mobility, and, growth])]). relacion([sujeto(['This']), verbo([requires]), complemento([a, 'multi-disciplinary', 'approach,', utilizing, pharmacological, 'interventions,', physical, 'therapy,', orthopedic, 'surgery,', and, monitoring, nutrition, with, appropriate, calcium, and, vitamin, 'D', supplementation])]). relacion([sujeto(['Bisphosphonate', 'therapy,', which]), verbo([has]), complemento([become, the, mainstay, of, treatment, in, 'OI,', has, proven, beneficial, in, increasing, bone, 'mass,', and, to, some, extent, reducing, fracture, risk])]). relacion([sujeto(['However,', resistance, to, chemotherapy]), verbo([has]), complemento([been, a, major, obstacle, in, the, management, of, 'NSCLC'])]). relacion([sujeto(['Aldehyde', dehydrogenase, 1, 'A1', '(', 'ALDH1A1)', overexpression]), verbo([has]), complemento([been, observed, in, a, variety, of, 'cancers,', including, lung, cancer])]). relacion([sujeto(['A', 3, -, '(', 4, ',', 5, -, 'dimethylthiazol-2-yl)-2,5-diphenyltetrazolium', bromide, assay, was, used, to, determine, the, effect, of, 'ALDH1A1']), verbo([decrease]), complemento([on, cell, viability])]). relacion([sujeto(['ALDH1A1', depletion, significantly]), verbo([decreased]), complemento(['A549/DDP', 'proliferation,', increased, 'apoptosis,', and, reduced, cisplatin, resistance])]). relacion([sujeto(['In', 'addition,', the, phosphoinositide, 3, -, kinase, '(', 'PI3K)', /, 'AKT', pathway, is]), verbo([activated]), complemento([in, 'A549/DDP,', and, 'ALDH1A1', knockdown, reduced, the, phosphorylation, level, of, 'AKT'])]). relacion([sujeto(['Moreover,', the, combination, of, 'ALDH1A1-short', hairpin, 'RNA', and, 'PI3K/AKT', pathway, inhibitor, 'LY294002', markedly]), verbo([inhibited]), complemento([cell, 'viability,', enhanced, apoptotic, cell, 'death,', and, increased, cisplatin, sensitivity])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, 'ALDH1A1', depletion, could, reverse, cisplatin, resistance, in, human, lung, cancer, cell, line, 'A549/DDP,', and, may, act, as, a, potential, target, for, the, treatment, of, lung, cancers, resistant, to, cisplatin])]). relacion([sujeto(['The', purpose, of, this, document, is, to, define, minimal, standards, for, a, flow, cytometry, shared, resource, laboratory, '(', 'SRL)', and]), verbo([provide]), complemento([guidance, for, best, practices, in, several, important, areas])]). relacion([sujeto(['This', effort, is, driven, by, the, desire, of, 'International', 'Society', for, the, 'Advancement', of, 'Cytometry', '(', 'ISAC)', members, in, 'SRLs', to, define, and]), verbo([maintain]), complemento([standards, of, excellence, in, flow, 'cytometry,', and, act, as, a, repository, for, key, elements, of, this, information, '(', e])]). relacion([sujeto(['In', 'monocots,', an, additional, phosphorylation, event, on, the, 'PSII', antenna, 'CP29', occurs, upon, exposure, to, excess, 'light,']), verbo([enhancing]), complemento([resistance, to, light, stress])]). relacion([sujeto(['Different', from, the, case, of, the, major, 'LHCII', antenna, 'complex,', the, 'STN7', kinase, and, its, related, 'PPH1', phosphatase, were, proven, not, to, be]), verbo([involved]), complemento([in, 'CP29', 'phosphorylation,', indicating, that, a, different, set, of, enzymes, act, in, the, 'high-light', response])]). relacion([sujeto(['Here,', we, analyze, a, rice, stn8, mutant, in, which, both, 'PSII', core, proteins, and, 'CP29', phosphorylation, are]), verbo([suppressed]), complemento([in, high, 'light,', implying, that, 'STN8', is, the, kinase, catalyzing, this, reaction])]). relacion([sujeto(['Based', on, these, 'data,', we, propose, that, the, activities, of, the, 'OsSTN8', kinase, and, the, antagonistic, 'OsPBCP', 'phosphatase,', in, addition, to, being]), verbo([involved]), complemento([in, the, repair, of, 'photo-damaged', 'PSII,', are, also, responsible, for, the, high, 'light-dependent', reversible, phosphorylation, of, the, inner, antenna, 'CP29'])]). relacion([sujeto(['We', present, here, mesoionic, carbenes, with, ferrocenyl, substituents, that, can]), verbo([act]), complemento([as, metalloligands, for, the, generation, of, heteromultimetallic, 'iridium(I)', and, 'gold(I)', complexes])]). relacion([sujeto(['The', ferrocenyl, substituents, allow, for, reversible, oxidation, of, these, heteromultimetallic, complexes, and, these, oxidation, steps]), verbo([have]), complemento([a, strong, influence, on, the, donor, properties, of, the, 'MICs'])]). relacion([sujeto(['It', is, a, trimeric, complex, composed, of, 'Snf1', protein, kinase, '(', orthologue, of, 'AMPKα', catalytic, 'subunit),', 'Snf4', '(', orthologue, of, 'AMPKγ', regulatory, 'subunit),', and, a, member, of, the, 'Gal83/Sip1/Sip2', family, of, proteins, '(', orthologues, of, 'AMPKβ', 'subunit)', that]), verbo([act]), complemento([as, scaffolds, and, also, regulate, the, subcellular, localization, of, the, complex])]). relacion([sujeto(['In', this, 'chapter,', we, review, the, recent, literature, on, the, characteristics, of, 'SNF1', complex, 'subunits,', the, structure, and, regulation, of, the, activity, of, the, 'SNF1', 'complex,', its, role, at, the, level, of, transcriptional, regulation, of, relevant]), verbo([target]), complemento([genes, and, also, at, the, level, of, posttranslational, modification, of, targeted, substrates])]). relacion([sujeto(['Rice', fields, are, an, important, source, of, nitrous, oxide, '(', 'N2O),', where, rice, plants, could]), verbo([act]), complemento([as, a, key, factor, controlling, 'N2O', fluxes, during, the, 'flooding-drying', 'process;', 'however,', the, microbial, driving, mechanisms, are, unclear])]). relacion([sujeto(['The', 'N2O', emission]), verbo([increased]), complemento([significantly, along, with, 'drying,', but, the, 'N2O', emission, capabilities, varied, among, the, four, zones, under, 'drying,', while, zone, 'B', possessed, the, highest, 'N2O', fluxes, that, were, 2.7, '~4'])]). relacion([sujeto(['This', study, demonstrates, that, drying]), verbo([caused]), complemento([significant, increase, in, 'N2O', emission, from, rhizosphere, 'soil,', in, which, the, higher, abundance, of, 'AOB', would, help, to, produce, more, nitrate, and, significantly, higher, 'narG-containing', microbes, would, drive, more, 'N2O', production, and, emission])]). relacion([sujeto(['The', mechanistic]), verbo([target]), complemento([of, rapamycin, '(', 'mTOR)', is, a, central, regulator, in, cell, 'growth,', 'activation,', 'proliferation,', and, survival])]). relacion([sujeto(['While', mTOR, activation, and, its, therapeutic, reversal, were, originally, discovered, in, 'T', 'cells,', recent, investigations]), verbo([have]), complemento([also, uncovered, roles, in, other, cell, subsets, including, 'B', 'cells,', 'macrophages,', and, &, 'quot;non-immune"', organs, such, as, the, liver, and, the, kidney])]). relacion([sujeto(['Activation', of, mTOR, complex, 1, '(', 'mTORC1)', precedes, the, onset, of, 'SLE', and]), verbo([associated]), complemento(['co-morbidities,', such, as, 'anti-phospholipid', syndrome, '(', 'APS),', and, may, act, as, an, early, marker, of, disease, pathogenesis])]). relacion([sujeto(['Six', case]), verbo([reports]), complemento([have, now, been, published, that, document, the, development, of, 'SLE', in, patients, with, genetic, activation, of, mTORC1])]). relacion([sujeto(['Targeting', mTORC1, 'over-activation', with, 'N-acetylcysteine,', 'rapamycin,', and, rapalogs]), verbo([provides]), complemento([an, opportunity, to, supplant, current, therapies, with, severe, side, effect, profiles, such, as, prednisone, or, cyclophosphamide])]). relacion([sujeto(['We', also, highlight, a, number, of, difficulties, when]), verbo([translating]), complemento([experimental, assays, into, 'GO', annotations])]). relacion([sujeto(['Both', 'miR-212', and, 'miR-132', are, usually, downregulated, in, ovarian, cancer, and]), verbo([act]), complemento([as, tumor, suppressors])]). relacion([sujeto(['Both', 'pri-miR-212', and, 'pri-miR-132', expressions]), verbo([decreased]), complemento([after, enforced, 'EZH2', or, 'SOX4', expression])]). relacion([sujeto(['Western', blot, and, 'dual-luciferase', assay, confirmed, that, 'miR-212', and, 'miR-132', can]), verbo([target]), complemento([the, same, sites, in, the, 3, '\'', 'UTR', of, 'SOX4', mRNA, and, suppress, its, expression, in, ovarian, cancer, cells])]). relacion([sujeto(['Therefore,', we, infer, that, the, 'SOX4/EZH2', complex, can, silence, 'miR-212', and, 'miR-132', expressions, via]), verbo([binding]), complemento([to, the, promoter, region, and, promoting, 'H3K27me3,', while, 'miR-212', and, 'miR-132', can, directly, bind, to, the, 3, '\'', 'UTR', of, 'SOX4', and, suppress, its, expression])]). relacion([sujeto(['Functionally,', 'SOX4', is, a, downstream, effector, of, 'miR-212/132']), verbo([modulating]), complemento(['EMT', of, ovarian, cancer, cells])]). relacion([sujeto(['The']), verbo([reported]), complemento([rate, of, 'AVN', following, closed, reduction, for, 'DDH', ranges, from, 4, to, 60, '%', ',', and, the, resultant, influence, on, hip, development, remains, unclear])]). relacion([sujeto(['This']), verbo([finding]), complemento([can, be, used, to, inform, the, feasibility, of, future, intervention, 'studies,', and, act, as, a, baseline, for, which, surgeons, to, compare, their, results, to, a, '\'', 'standard\''])]). relacion([sujeto(['Adoptive', 'T', cell, transfer]), verbo([has]), complemento([been, shown, to, be, an, effective, method, used, to, boost, 'tumor-specific', immune, responses, in, several, types, of, malignancies])]). relacion([sujeto(['In', 'summary,', our, results]), verbo([suggest]), complemento([that, the, 'ACT', approach, together, with, 'LNCaP-loaded', dendritic, cells, provides, a, viable, way, to, generate, prostate, cancer, reactive, 'T', cell, effectors, that, are, capable, of, mounting, efficient, and, targeted, antitumor, responses, and, can, be, thus, considered, for, further, testing, in, a, clinical, setting])]). relacion([sujeto(['Preclinical', models, and, studies, in, the, metastatic, and, neoadjuvant, settings]), verbo([suggest]), complemento([that, single, nucleotide, polymorphisms, in, 'FCGR3A', and, 'FCGR2A', may, be, associated, with, differential, response, to, trastuzumab, in, the, treatment, of, 'ERBB2/HER2-positive', breast, 'cancer,', by, modulating, 'antibody-dependent', 'cell-mediated', cytotoxic, effects])]). relacion([sujeto(['Patients', who, are, homozygous, for, phenylalanine, at, this, position, represent, a, considerable, proportion, of, the, population, 'and,', in, contrast, to, previously]), verbo([reported]), complemento([analyses, from, similarly, designed, 'trials,', our, results, indicate, that, trastuzumab, may, be, less, efficacious, in, these, patients])]). relacion([sujeto(['PCR-RFLP']), verbo([targeting]), complemento([18, 'S', ribosomal, 'RNA', '(', 'rRNA)', genes, was, also, performed, on, all, samples, to, detect, other, apicomplexan, parasites])]). relacion([sujeto([gondii, is, commonly, present, in, wild, 'mammals,', which]), verbo([act]), complemento([as, sources, of, infection, for, humans, and, 'animals,', including, other, wild, species])]). relacion([sujeto(['Resulting', policies, were]), verbo([led]), complemento([by, equivocal, evidence, for, improved, tobacco, control, outcomes, among, 'Indigenous', 'Australians'])]). relacion([sujeto(['Other', policy, makers]), verbo([recognized]), complemento([that, there, were, barriers, to, accumulating, 'rigorous,', generalizable, 'evidence;', in, the, absence, of, such, 'evidence,', the, policy, makers, considered, that, the, &, 'quot;need', for, 'action"', could, be, combined, with, the, &, 'quot;need', for, 'research"', by, introducing, innovative, strategies, and, evaluating, them])]). relacion([sujeto(['Molybdenum', disulfide, '(', 'MoS2)']), verbo([has]), complemento([attracted, a, great, attention, as, an, excellent, 2, 'D', material, for, future, optoelectronic, devices])]). relacion([sujeto(['When', an, external, friction, layer, produces, a, relative, sliding, on, the, 'device,', the]), verbo([induced]), complemento([positive, charges, on, the, back, gate, of, the, 'MoS2', phototransistor, act, as, a, &, 'quot;gate"', to, increase, the, channel, conductivity, as, the, traditional, back, gate, voltage, does])]). relacion([sujeto(['With', the, sliding, distance, 'increases,', the, photoresponsivity, of, the, device, is, drastically]), verbo([enhanced]), complemento([from, 221.0, to, 727.8, 'A', 'W(-1)', at, the, 100, mW, 'cm(-2)', 'UV', excitation, intensity, and, 1, 'V', bias, voltage])]). relacion([sujeto(['This', work]), verbo([has]), complemento([extended, the, emerging, tribotronics, to, the, field, of, photodetection, based, on, 2, 'D', 'material,', and, demonstrated, a, new, way, to, realize, the, adjustable, photoelectric, devices, with, high, photoresponsivity, via, human, interfacing])]). relacion([sujeto(['Ephemeral', rivers]), verbo([act]), complemento([as, linear, oases, in, drylands, providing, key, resources, to, people, and, wildlife])]). relacion([sujeto(['We']), verbo([found]), complemento([widespread, dieback, in, both, tree, 'populations:', 51, '%', mortality, in, ana, 'tree,', with, surviving, trees, exhibiting, 18, '%', canopy, death, '(', 'median);', and, 26, '%', mortality, in, 'mesquite,', with, surviving, trees, exhibiting, 10, '%', canopy, death])]). relacion([sujeto(['Our', findings]), verbo([suggest]), complemento([that, dieback, in, the, ana, tree, is, primarily, driven, by, changes, in, river, flow, resulting, from, upstream, dam, creation, and, that, tributary, flows, provide, a, local, buffer, against, this, loss, of, main, channel, flow])]). relacion([sujeto(['Our', findings]), verbo([suggest]), complemento([that, large, dams, along, the, main, channels, of, ephemeral, rivers, have, the, ability, to, cause, widespread, mortality, in, downstream, riparian, trees])]). relacion([sujeto(['However,', the, existence, of, local, variation, in, selfless, behaviour, within, populations]), verbo([has]), complemento([received, relatively, little, empirical, attention])]). relacion([sujeto(['We', predicted, that, there, is, a, positive, association, between, suburb, socioeconomic, status, and, number, of, letters, returned, and, that, altruistic]), verbo([acts]), complemento([decrease, in, frequency, when, costs, 'increase,', even, minimally])]). relacion([sujeto(['Rates', of, hybridization, and, introgression, are]), verbo([increasing]), complemento([dramatically, worldwide, because, of, 'translocations,', restocking, of, organisms, and, habitat, 'modifications;', 'thus,', determining, whether, hybridization, is, occuring, after, reintroducing, extirpated, congeneric, species, is, commensurately, important, for, conservation])]). relacion([sujeto(['We']), verbo([have]), complemento([confirmed, restocked, riverine, 'Trout', 'Cod', 'reproducing,', but, only, as, 'inter-specific', 'matings,', in, the, wild])]). relacion([sujeto(['Although', hybrid, 'larvae,', juveniles, and, adults]), verbo([have]), complemento([been, recorded, in, hatcheries, and, 'impoundments,', and, hybrid, adults, have, been, recorded, in, rivers, 'previously,', this, is, the, first, time, fertile, 'F1', have, been, recorded, in, a, wild, riverine, population])]). relacion([sujeto(['The', 'F1', backcrosses, with, 'Murray', cod]), verbo([have]), complemento([also, been, found, to, be, fertile])]). relacion([sujeto(['Such', introgression]), verbo([has]), complemento([not, been, recorded, previously, in, these, two, 'species,', and, the, imbalance, in, hybridization, direction, may, have, important, implications, for, restocking, programs])]). relacion([sujeto(['This', model]), verbo([suggests]), complemento([that, a, genetic, disease, is, the, result, of, the, combination, of, several, common, genetic, variants])]). relacion([sujeto(['However,', rare, 'variants,', rather, than, common, 'variants,']), verbo([have]), complemento([been, found, in, numerous, genome, wide, genetic, studies, and, many, have, concluded, that, the, &, 'quot;common', 'variant-common', 'disease"', hypothesis, is, incorrect])]). relacion([sujeto(['One', interpretation, is, that, rare, variants, are, major, contributors, to, genetic, diseases, and, autism]), verbo([involves]), complemento([the, interaction, of, many, rare, 'variants,', especially, in, the, brain])]). relacion([sujeto(['Evidence']), verbo([has]), complemento([been, mounting, over, the, years, indicating, immune, involvement, in, 'autism,', particularly, the, 'HLA', genes, on, chromosome, 6, and, 'KIR', genes, on, chromosome, 19])]). relacion([sujeto(['These', two, large, multigene, complexes]), verbo([have]), complemento([important, immune, functions, and, have, been, shown, to, interact, to, eliminate, unwanted, virally, infected, and, malignant, cells])]). relacion([sujeto(['HLA', proteins]), verbo([have]), complemento([important, functions, in, antigen, presentation, in, adaptive, immunity, and, specific, epitopes, on, 'HLA', class, 'I', proteins, act, as, cognate, ligands, for, 'KIR', receptors, in, innate, immunity])]). relacion([sujeto(['Data']), verbo([suggests]), complemento([that, 'HLA', alleles, and, 'KIR', activating, 'genes/haplotypes', are, common, variants, in, different, autism, populations])]). relacion([sujeto(['For', 'example,', class, 'I', allele, '(', 'HLA-A2', and, 'HLA-G', 14, 'bp-indel)', frequencies, are, significantly]), verbo([increased]), complemento([by, more, than, 5, '%', over, control, populations, '(', 'Table', 2, ')'])]). relacion([sujeto(['Three']), verbo([activating]), complemento(['KIR', 'genes:', 3, 'DS1,', 2, 'DS1,', and, 2, 'DS2', have, increased, frequencies, of, 15, ',', 22, ',', and, 14, '%', in, autism, 'populations,', respectively])]). relacion([sujeto(['There', is, a, 6, '%']), verbo([increase]), complemento([in, total, activating, 'KIR', genes, in, autism, over, control, subjects])]). relacion([sujeto(['And,', more, importantly, there, is, a, 12, '%']), verbo([increase]), complemento([in, activating, 'KIR', genes, and, their, cognate, 'HLA', alleles, over, control, populations, '(', 'Torres', et, al])]). relacion([sujeto(['These', data]), verbo([suggest]), complemento([the, interaction, of, 'HLA', 'ligand/KIR', receptor, pairs, encoded, on, two, different, chromosomes, is, more, significant, as, a, 'ligand/receptor', complex, than, separately, in, autism])]). relacion([sujeto(['Yellow-related', proteins, '(', 'YRPs)', present, in, sand, fly, saliva]), verbo([act]), complemento([as, affinity, binders, of, 'bioamines,', and, help, the, fly, to, complete, a, bloodmeal, by, scavenging, the, physiological, signals, of, damaged, cells])]). relacion([sujeto(['Moreover,', several, salivary, proteins, and, plasmids, coding, these, proteins]), verbo([induce]), complemento([strong, immune, response, in, hosts, bitten, by, sand, flies, and, are, being, used, to, design, protecting, vaccines, against, 'Leishmania', parasites])]). relacion([sujeto(['However,', intraspecific, modifications]), verbo([found]), complemento([among, these, proteins, affects, the, charges, of, the, entrances, to, the, 'tunnel,', the, length, of, the, tunnel, and, its, hydrophobicity])]). relacion([sujeto(['We']), verbo([suggest]), complemento([that, these, structural, and, sequential, differences, influence, the, 'ligand-binding', abilities, of, these, proteins, and, provide, sand, flies, with, a, greater, number, of, 'YRP', paralogs, with, more, nuanced, answers, to, bioamines])]). relacion([sujeto(['Unprincipled', modeling, decisions, in, 'large-domain', 'ontologies,', such, as, 'SNOMED', 'CT,', are, problematic, and, might]), verbo([act]), complemento([as, a, barrier, for, their, quality, assurance, and, successful, use, in, electronic, health, records])]). relacion([sujeto(['Most', previous, work]), verbo([has]), complemento([focused, on, clustering, problematic, 'concepts,', which, is, helpful, for, quality, control, but, faces, difficulties, in, pinpointing, the, origin, of, those, modeling, problems])]). relacion([sujeto(['Our', results, showed, that, 92, '%', of, all, structural, patterns]), verbo([found]), complemento([accumulated, in, the, 'Procedure', and, 'Clinical', finding, 'sub-hierarchies,', and, pattern, reuse, was, 'low;', over, 30, '%', of, patterns, were, only, used, once])]). relacion([sujeto(['The', problems, detected, in, the, sample]), verbo([suggest]), complemento([that, the, analysis, of, structural, patterns, is, a, valuable, technique, for, revealing, problematic, areas, of, 'SNOMED', 'CT', and, modeling, the, styles, of, terminology, editors])]). relacion([sujeto(['Furthermore,', the, patterns, that, describe, the, modeling, of, a, large, number, of, concepts, could]), verbo([provide]), complemento([insights, for, template, creation, and, refinement, in, 'SNOMED', 'CT'])]). relacion([sujeto(['To']), verbo([prevent]), complemento(['WSe2', film, peeling, off, from, the, substrate, during, 'selenization,', the, 'W', film, was, designed, with, a, 'double-layer', structure])]). relacion([sujeto(['The', first, layer, was, deposited, at, a, high, 'sputtering-gas', pressure, to, form, a, loose, 'structure,', which, can]), verbo([act]), complemento([as, a, buffer, layer, to, release, stresses, caused, by, 'WSe2', growth])]). relacion([sujeto(['Shortening', the, sputtering, 'time,']), verbo([increasing]), complemento([the, 'sputtering-gas', pressure, or, decreasing, the, substrate, bias, voltage, can, help, synthesize, 'WSe2', films, with, more, platelets, embedded, vertically, in, the, matrix])]). relacion([sujeto(['Afforestation', also]), verbo([enhanced]), complemento([the, 'F:', 'B', ratios, compared, with, cropland])]). relacion([sujeto(['The', basal, microbial, respiration, was, higher, while, the, basal, microbial, respiration, on, a, 'per-unit-PLFA', basis, was, lower, in, afforested, land, than, adjacent, cropland, and, uncultivated, 'land,']), verbo([suggesting]), complemento([afforestation, may, increase, soil, 'C', utilization, efficiency, and, decrease, respiration, loss, in, afforested, soils])]). relacion([sujeto(['Fretting', is, a, significant]), verbo([cause]), complemento([for, the, failure, of, orthopedic, implants])]). relacion([sujeto(['Currently,', since, magnesium, and, its, alloys]), verbo([have]), complemento([been, developed, as, promising, biodegradable, implant, 'materials,', the, fretting, behavior, of, the, 'Mg', alloys, is, of, great, research, significance])]). relacion([sujeto(['The', results, indicated, that, while, the, friction, coefficient]), verbo([decreased]), complemento([with, the, increment, of, the, normal, 'load,', the, wear, volume, of, the, alloy, increased, with, the, increment, of, the, normal, load, both, in, air, and, in, 'Hank\'s', solution])]). relacion([sujeto(['Moreover,', the, addition, of, 'Fetal', bovine, serum, '(', 'FBS)', could]), verbo([act]), complemento([as, lubrication, and, result, in, the, reduction, of, the, fretting, damage])]). relacion([sujeto(['The', transfer, of, mobile, genetic, elements, such, as, plasmids, '(', 'conjugation)']), verbo([requires]), complemento([the, close, proximity, of, cells])]). relacion([sujeto(['Our', study, shows, that, the, network, structures, of, mycelia]), verbo([promote]), complemento([bacterial, 'HGT', by, providing, continuous, liquid, films, in, which, bacterial, migration, and, contacts, are, favoured])]). relacion([sujeto(['This']), verbo([finding]), complemento([was, confirmed, by, 'individual-based', 'simulations,', revealing, that, the, tendency, of, migrating, bacteria, to, concentrate, in, the, liquid, film, around, hyphae, is, a, key, factor, for, improved, 'HGT', along, mycelial, networks])]). relacion([sujeto(['Given', their, 'ubiquity,', we, propose, that, hyphae, can]), verbo([act]), complemento([as, focal, point, for, 'HGT', and, genetic, adaptation, in, soil])]). relacion([sujeto(['Like', many, 'Pyrrhura', 'species,', it, is, mostly, 'green,', and]), verbo([has]), complemento([a, pale, auricular, 'patch,', red, tail, and, 'belly,', but, presents, a, bright, red, 'head,', distinct, from, any, other, close, relatives, within, the, genus])]). relacion([sujeto([picta, '(', 'Statius', 'Miller,', 1776, ')', '(', 'Arndt', 1983, ;, 'Arndt', 1996, ;, 'Collar', 1997, ;, 'Juniper', &, 'amp;', 'Parr,', 1998, ')', and, only, recently]), verbo([has]), complemento([its, specific, rank, been, restored, '(', 'Joseph', 2000, ',', 2002, ;, 'Ribas', et, al])]). relacion([sujeto(['(', 'Rutaceae)']), verbo([have]), complemento([been, identified, as, native, hosts, of, 'T'])]). relacion([sujeto(['We']), verbo([report]), complemento([such, a, case, with, the, discovery, and, description, of, 'U'])]). relacion([sujeto(['We']), verbo([provide]), complemento([details, of, its, 'morphology,', 'calls,', embryos, and, 'tadpoles,', and, phylogenetic, relationships, to, other, species, of, eastern, 'Uperoleia'])]). relacion([sujeto(['We', also]), verbo([provide]), complemento([the, results, of, targeted, surveys, to, establish, its, distribution, and, provide, observations, of, its, habitat, associations])]). relacion([sujeto(['We', note, this, 'species,', which, is, morphologically, 'distinct,']), verbo([has]), complemento([gone, unnoticed, for, many, decades, despite, numerous, ecological, surveys, for, local, development, applications])]). relacion([sujeto(['A', number, of, metallo, derivatives, of, 5, ',', 10, ',', 15, ',', 20, -, 'tetrakis(4-cyanophenyl)porphyrin,', where, the, 'N', atom, of, the, linear, cyano, group, can]), verbo([act]), complemento([both, as, a, donor, for, coordination, bonds, or, as, an, acceptor, for, hydrogen, 'bonds,', have, been, structurally, characterized, by, 'single-crystal', 'X-ray', analysis])]). relacion([sujeto(['The', supramolecular, and, structural, chemistry, of, the, corresponding, 2, -, and, 3, -, cyanophenyl, isomers, of, the, parent, 'porphyrin,', 'however,']), verbo([has]), complemento([remained, largely, unexplored])]). relacion([sujeto(['The', crystal, structure, of, '[', 5, ',', 10, ',', 15, ',', 20, -, 'tetrakis(3-cyanophenyl)porphyrinato]copper(II)', '(', 'CuTCNPP)', nitrobenzene, 'trisolvate,', '[', 'Cu(C48H24N8)]·3C6H5NO2,']), verbo([has]), complemento([been, determined, at, 80, 'K', by, synchrotron, 'single-crystal', 'X-ray', diffraction])]). relacion([sujeto(['Polynuclear', complexes, and, coordination, polymers, of, 3, d, metals]), verbo([have]), complemento([attracted, significant, interest, evoked, by, a, number, of, their, unique, properties])]). relacion([sujeto(['Tris(pyrazolyl)borates', '(', 'Tp)']), verbo([act]), complemento([as, tripodal, '`capping\'', ligands, which, form, stable, complexes, with, 3, d, metal, ions])]). relacion([sujeto(['They', possess, similar, molecular, 'structures,', 'X-ray', diffraction]), verbo([revealed]), complemento([them, to, be, dinuclear, in, nature, and, composed, of, discrete, 'Tp-M', units, in, which, two, metal, ions, are, linked, by, a, 'tae(2-)', dianion])]). relacion([sujeto(['The', thoracic, spiracles, opened, much, quicker, '(', approximately, 0.1, 's)', than, they, closed, '(', 1, 's)']), verbo([suggesting]), complemento([that, the, spiracular, muscles, are, 'openers,', confirmed, by, experimental, induction, of, muscle, contraction])]). relacion([sujeto(['Simultaneous', photocell, measurement, revealed, that, the, first, and, second, thoracic, spiracles]), verbo([act]), complemento([concordantly])]). relacion([sujeto(['During', long, spontaneous, continuous, flight, phases, '(', up, to, two, 'hours)', the, valves, were, only, slightly, open, '(', below, 5, '%', ')', ',', widening, shortly, after, transient]), verbo([increases]), complemento([of, wing, stroke, intensity])]). relacion([sujeto(['The', advantage, of, generating, 'sub-atmospheric', 'pressure,', supporting, a, unidirectional, airflow, with, a, 'PO2']), verbo([increase]), complemento([above, the, resting, 'level,', is, discussed])]). relacion([sujeto(['Carica', papaya, '(', 'papaya)', seed, germinate, readily, fresh, from, the, 'fruit,', but, desiccation]), verbo([induces]), complemento([a, dormant, state])]). relacion([sujeto(['Dormancy', can, be]), verbo([released]), complemento([by, exposure, of, the, hydrated, seed, to, a, pulse, of, elevated, 'temperature,', typical, of, that, encountered, in, its, tropical, habitat])]). relacion([sujeto(['Here', we, investigate, the, mechanisms, that]), verbo([mediate]), complemento(['HS-induced', stimulation, of, germination, in, 'pre-dried', and, 're-imbibed', papaya, seed])]). relacion([sujeto(['However,', 'HS', did, not, sensitise, seeds, to, 'GA3,', indicative, that, it, may]), verbo([act]), complemento([independently, of, 'GA', biosynthesis])]). relacion([sujeto(['However,', cycloheximide]), verbo([prevented]), complemento([both, seed, coat, weakening, and, 'germination,', implicating, a, requirement, for, de, novo, protein, synthesis, in, both, processes])]). relacion([sujeto(['The', germination, antagonist, abscisic, acid]), verbo([prevented]), complemento([radicle, emergence, but, had, no, effect, on, papaya, seed, coat, weakening])]). relacion([sujeto(['The', ability, to, germinate, in, response, to, a, 'HS', may]), verbo([confer]), complemento([a, competitive, advantage, to, 'C'])]). relacion([sujeto(['Exposure', of, 'Arabidopsis', to, high, concentrations, of, 'NO2']), verbo([induced]), complemento([cell, death, in, a, 'dose-dependent', manner])]). relacion([sujeto(['No', leaf, symptoms, were, visible, after, fumigation, for, 1, h, with, 10, parts, per, million, '(', 'ppm)', 'NO2', 'However,', 20, ppm, 'NO2']), verbo([caused]), complemento([necrotic, lesion, formation, and, 30, ppm, 'NO2', complete, leaf, 'collapse,', which, had, already, started, during, the, 1, h, fumigation, period])]). relacion([sujeto(['Nitric', oxide, '(', 'NO)', at, 30, ppm, did, not]), verbo([trigger]), complemento([leaf, damage, or, any, of, the, effects, observed, after, 'NO2', fumigation])]). relacion([sujeto(['The', onset, of, 'NO2-induced', cell, death, correlated, with, 'NO', and, hydrogen, peroxide, '(', 'H2O2)', signaling, and, a]), verbo([decrease]), complemento([in, antioxidants])]). relacion([sujeto(['Leaf', injection, of, 100, mM, nitrite]), verbo([caused]), complemento([an, increase, in, 'S-nitrosylation,', 'NO,', 'H2O2,', and, cell, death, suggesting, that, nitrite, functioned, as, a, mediator, of, 'NO2-induced', effects])]). relacion([sujeto(['A']), verbo([targeted]), complemento([screening, of, phytohormone, mutants, revealed, a, protective, role, of, salicylic, acid, '(', 'SA)', signaling, in, response, to, 'NO2', 'It', was, also, shown, that, phytohormones, were, modulators, rather, than, inducers, of, 'NO2-induced', cell, death])]). relacion([sujeto(['Age', at, onset, '(', 'AAO)', in, multiple, sclerosis, '(', 'MS)', is, an, important, marker, of, disease, severity, and, may]), verbo([have]), complemento([prognostic, significance])]). relacion([sujeto(['Understanding', what, factors, can, influence, 'AAO', may, shed, light, on, the, aetiology, of, this, complex, 'disease,', and]), verbo([have]), complemento([applications, in, the, diagnostic, process])]). relacion([sujeto(['A', reciprocal, relationship, was, seen, for, ambient, ultraviolet, radiation, '(', 'UVR),', with, a, significantly]), verbo([increasing]), complemento(['AAO', for, patients, with, 'MS', per, each, quartile, increment, of, ambient, 'UVR', '(', 'p=1'])]). relacion([sujeto(['We']), verbo([found]), complemento([that, the, 'AAO', of, female, patients, was, '∼5', months, earlier, than, male, patients, '(', 'p=0'])]). relacion([sujeto(['An', earlier, 'AAO', in, higher, latitude, regions, was]), verbo([found]), complemento([in, this, worldwide, 'European-descent', cohort, and, correlated, inversely, with, variation, in, latitudinal, 'UVR'])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, environmental, factors, which, act, at, the, population, level, may, significantly, influence, disease, severity, characteristics, in, genetically, susceptible, populations])]). relacion([sujeto(['Potentiation', of, glutamatergic, tone]), verbo([has]), complemento([been, causally, related, to, the, sympathoexcitation, in, 'CHF'])]). relacion([sujeto(['Specifically,', an]), verbo([increase]), complemento([in, the, 'N-methyl-d-aspartate-type', 1, receptor, '(', 'NMDA-NR1)', expression, within, the, paraventricular, nucleus, '(', 'PVN)', is, critically, linked, to, the, increased, sympathoexcitation, during, 'CHF'])]). relacion([sujeto(['In', neuronal, cell, line, '(', 'NG108-15)', in, 'vitro,', hypoxia]), verbo([caused]), complemento([a, significant, increase, in, mRNA, and, protein, for, 'HIF-1α', '(', 2, -, 'fold)', with, the, concomitant, increase, in, 'NMDA-NR1', 'mRNA,', protein, 'levels,', and, 'glutamate-induced', 'Ca(+)', influx])]). relacion([sujeto(['Chromatin', immunoprecipitation, assay, identified, 'HIF-1α']), verbo([binding]), complemento([to, 'NMDA-NR1', promoter, during, hypoxia])]). relacion([sujeto(['Silencing', of, 'HIF-1α', in, 'NG108', cells]), verbo([leads]), complemento([to, a, significant, decrease, in, expression, of, 'NMDA-NR1,', suggesting, that, expression, of, 'HIF-1α', is, necessary, for, the, upregulation, of, 'NMDA-NR1'])]). relacion([sujeto(['Consistent', with, these, 'observations,', 'HIF-1α', silencing, within, the, 'PVN', abrogated, the]), verbo([increased]), complemento([basal, sympathetic, tone, and, sympathoexcitatory, responses, to, microinjection, of, 'NMDA', in, the, 'PVN', of, rats, with, 'CHF'])]). relacion([sujeto(['These', results, uncover, a, critical, role, for, 'HIF-1', in, the, upregulation, of, 'NMDA-NR1', to]), verbo([mediate]), complemento([sympathoexcitation, in, 'CHF'])]). relacion([sujeto(['We', conclude, that, subtle, hypoxia, within, the, 'PVN', may]), verbo([act]), complemento([as, a, metabolic, cue, to, modulate, sympathoexcitation, during, 'CHF'])]). relacion([sujeto(['Tyrosinase', is]), verbo([involved]), complemento([in, the, production, of, melanin, through, the, hydroxylation, of, monophenols, to, 'o-diphenols'])]). relacion([sujeto(['The', role, of, this, enzyme, was, extensively, studied, in, order, to, identify, new, therapeutics]), verbo([preventing]), complemento([skin, pigmentation, and, melanoma])]). relacion([sujeto(['The', inhibition, kinetics, analyzed, by, 'Lineweaver-Burk', plots, revealed, that, compounds, 2, 'a-c', and, 10, b]), verbo([act]), complemento([as, 'non-competitive', inhibitors, while, the, most, active, inhibitor, 2, d, '(', 'IC50 = 7'])]). relacion([sujeto(['Furthermore,', experimental, and, computational, structural, studies, were, performed, in, order, to, clarify, the]), verbo([binding]), complemento([mode, of, the, derivative, 2, d])]). relacion([sujeto(['Certain', 'ATP']), verbo([binding]), complemento([cassette, '(', 'ABC)', transporter, 'proteins,', such, as, zebrafish, 'Abcb4,', are, efflux, pumps, acting, as, a, cellular, defence, against, a, wide, range, of, 'different,', potentially, toxic, chemical, compounds, thus, mediating, so, called, multixenobiotic, resistance, '(', 'MXR)'])]). relacion([sujeto(['Certain', chemicals]), verbo([target]), complemento(['MXR', proteins, 'and,', as, so, called, 'chemosensitisers,', inhibit, the, activity, of, these, proteins, thus, increasing, the, toxicity, of, other, chemicals, that, would, normally, be, effluxed])]). relacion([sujeto(['For', seven, compounds, rhodamine, tissue, levels, were, either, both]), verbo([decreased]), complemento([and, increased, depending, on, the, compound, concentration, indicating, both, stimulation, and, inhibition, of, rhodamine, 123, efflux, by, those, 'compounds,', only, increased, '(', 'inhibition,', six, 'compounds)', or, only, decreased, '(', 'stimulation,', one, 'compound)'])]). relacion([sujeto(['Recombinant', zebrafish, 'Abcb4', was, obtained, with, the, baculovirus, expression, system, and, 'PPCPs', were, tested, for, 'stimulation/inhibition', of, basal, transporter, 'ATPase', activity, and, for, inhibition, of, the, transporter, 'ATPase', activity]), verbo([stimulated]), complemento([with, verapamil])]). relacion([sujeto(['Eight', of, the, tested, 'PPCPs', showed, effects, on, 'Abcb4', 'ATPase', activity, indicating, that, their, effects, in, the, dye, accumulation, assay, may]), verbo([have]), complemento([indeed, resulted, from, interference, with, 'Abcb4-mediated', rhodamine, 123, efflux])]). relacion([sujeto(['Slight', stimulatory, effects, were]), verbo([found]), complemento([for, musk, 'xylene,', 'nerol,', 'isoeugenol,', 'α-amylcinnamaldehyde,', 'α-hexylcinnamaldehyde', and, simvastatin, indicating, 'Abcb4', 'substrate/competitive', inhibitor, properties, of, those, compounds])]). relacion([sujeto(['Likewise,']), verbo([decreases]), complemento([of, the, 'verapamil-stimulated', 'Abcb4', 'ATPase', activity, by, diclofenac, and, fluoxetine, may, indicate, competitive, transporter, inhibition])]). relacion([sujeto(['Sertraline']), verbo([inhibited]), complemento([the, basal, and, 'verapamil-stimulated', 'Abcb4', 'ATPase', activities, suggesting, its, property, as, 'non-competitive', 'Abcb4', inhibitor])]). relacion([sujeto(['Taken', 'together,', our]), verbo([finding]), complemento([that, chemically, diverse, 'PPCPs', interfere, with, 'MXR', efflux, activity, of, zebrafish, indicates, that, '(', 1, ')', efflux, transporters, may, influence, bioaccumulation, of, many, 'PPCPs', in, fish, and, that, '(', 2, ')', many, 'PPCPs', may, act, as, chemosensitisers])]). relacion([sujeto(['Sporulation', can, occur, all, along, the, food, 'chain,', in, raw, 'materials,', but, also, in, food, 'processes,']), verbo([leading]), complemento([to, an, increase, in, food, contamination])]). relacion([sujeto(['Some', environmental, factors, are]), verbo([required]), complemento([to, trigger, this, differentiation, process, and, others, act, by, modulating, it])]). relacion([sujeto(['Serotonergic', hallucinogens, produce, alterations, of, 'perceptions,', 'mood,', and, 'cognition,', and]), verbo([have]), complemento(['anxiolytic,', 'antidepressant,', and, antiaddictive, properties])]). relacion([sujeto(['These', drugs]), verbo([act]), complemento([as, agonists, of, frontocortical, 5, -, 'HT2A', 'receptors,', but, the, neural, basis, of, their, effects, are, not, well, understood])]). relacion([sujeto(['Long-term', use, was]), verbo([associated]), complemento([with, thinning, of, the, posterior, cingulate, 'cortex,', thickening, of, the, anterior, cingulate, 'cortex,', and, decreased, neocortical, 5, -, 'HT2A', receptor, binding])]). relacion([sujeto(['Despite', the, high, methodological, heterogeneity, and, the, small, sample, 'sizes,', the, results]), verbo([suggest]), complemento([that, hallucinogens, increase, introspection, and, positive, mood, by, modulating, brain, activity, in, the, 'fronto-temporo-parieto-occipital', cortex])]). relacion([sujeto(['A', series, of, monomeric, and, dimeric, 'Fe(III)', complexes, with, 'O,O-;', 'O,N-;', 'O,S-coordination', motifs]), verbo([has]), complemento([been, prepared, and, characterized, by, standard, analytical, methods, in, order, to, elucidate, their, potential, to, act, as, model, compounds, for, aquatic, humic, acids])]). relacion([sujeto(['Additionally,', observed, reduction, processes, were, predominantly, 'irreversible,']), verbo([suggesting]), complemento([that, subsequent, reactions, can, take, place, after, reduction, of, the, iron, center])]). relacion([sujeto(['The', ability, to]), verbo([act]), complemento([as, an, iron, source, for, primary, producers, was, tested, in, algal, growth, experiments, with, two, marine, algae, species, 'Chlorella', salina, and, 'Prymnesium', parvum])]). relacion([sujeto(['Those', findings, help, to, understand, which, functional, groups, of, humic, acids, could, be, responsible, for, the, reversible, iron]), verbo([binding]), complemento([and, transport, in, aquatic, humic, substances])]). relacion([sujeto(['The', propionic, acids, of, heme, a3]), verbo([have]), complemento([been, proposed, to, act, as, a, proton, loading, site, '(', 'PLS)', in, the, proton, pumping, 'pathway,', yet, this, proposal, could, not, be, verified, by, experimental, data, so, far])]). relacion([sujeto(['We']), verbo([have]), complemento([set, up, an, experiment, where, the, redox, states, of, the, two, hemes, in, 'CcO', can, be, controlled, via, external, electrical, potential])]). relacion([sujeto(['Surface']), verbo([enhanced]), complemento([resonance, 'Raman', '(', 'SERR)', spectroscopy, was, applied, to, simultaneously, monitor, the, redox, state, of, the, hemes, and, the, protonation, state, of, the, heme, propionates])]). relacion([sujeto(['Simulated', spectra, based, on, 'QM/MM', calculations, were, used, to, assign, the, resonant]), verbo([enhanced]), complemento(['CH2', twisting, modes, of, the, propionates, to, the, protonation, state, of, the, individual, heme, a, and, heme, a3, propionates, respectively])]). relacion([sujeto(['In', the, fully, reduced, enzyme, at, least, three, of, the, four, heme, propionates, were]), verbo([found]), complemento([to, be, protonated, whereas, in, the, presence, of, a, reduced, heme, a, and, an, oxidized, heme, a3, only, protonation, of, one, heme, a3, propionates, was, observed])]). relacion([sujeto(['Our', data, supports, the, postulated, scenario, where, the, heme, a3, propionates, are]), verbo([involved]), complemento([in, the, proton, pathway])]). relacion([sujeto(['Our', findings]), verbo([suggest]), complemento(['that:', what, people, value, ranges, from, abstract, to, 'concrete;', prevalent, abstract, values, include, benevolence, and, 'universalism;', prevalent, 'mid-level', valued, attributes, include, natural, attributes, of, landscapes, and, human, life, and, 'welfare;', prevalent, valued, entities, are, people, and, properties, close, to, the, person])]). relacion([sujeto(['Comparison', between, the, two, studies]), verbo([suggests]), complemento([people, with, more, recent, experience, with, bushfire, refer, less, to, the, importance, of, natural, places, and, natural, attributes])]). relacion([sujeto(['The', conceptual, framework, can]), verbo([act]), complemento([as, a, boundary, object, to, facilitate, researchers, and, 'policy-makers', understanding, the, breadth, of, values, affected, by, natural, disaster, events, and, management, actions, and, how, governance, can, better, consider, values, at, different, scales])]). relacion([sujeto(['Obesity-related', lifestyle, behaviors, usually, 'co-exist', but, few, studies]), verbo([have]), complemento([examined, their, simultaneous, relation, with, body, weight])]). relacion([sujeto(['This', study, aimed, to, identify, the, hierarchy, of, 'lifestyle-related', behaviors]), verbo([associated]), complemento([with, being, overweight, in, 'adults,', and, to, examine, subgroups, so, identified])]). relacion([sujeto(['Participants', also]), verbo([reported]), complemento([their, weight, and, height])]). relacion([sujeto(['Different', combinations, of, 'lifestyle-related', behaviors, '(', prolonged, daily, television, 'viewing,', former, 'smoking,', short, 'sleep,', lower, vegetable, 'consumption,', and, lower, physical, 'activity)', were]), verbo([associated]), complemento([with, a, higher, likelihood, of, being, 'overweight,', revealing, 10, subgroups])]). relacion([sujeto(['Delineating', the, hierarchy, of, correlates]), verbo([provides]), complemento([a, better, understanding, of, 'lifestyle-related', behavior, combinations, which, may, assist, in, targeting, preventative, strategies, aimed, at, tackling, obesity])]). relacion([sujeto(['Malaria', is, a, major]), verbo([cause]), complemento([of, morbidity, and, mortality, in, many, 'African', countries, and, parts, of, 'Asia', and, 'South', 'America'])]). relacion([sujeto(['Novel', approaches, to, combating, the, disease]), verbo([have]), complemento([emerged, in, recent, years, and, several, drug, candidates, are, now, being, tested, clinically])]). relacion([sujeto(['Aminoquinoline-based', scaffolds, such, as, ferroquine, are, promising, but, should, be, combined, with, good, partner, drugs, for]), verbo([enhanced]), complemento([efficacy])]). relacion([sujeto(['AQ-13']), verbo([induced]), complemento([electrocardiac, 'events,', which, led, to, prolonged, 'QTc', intervals])]). relacion([sujeto(['Tafenoquine,', the, only, new, 'anti-relapse', scaffold, for, patients, with, a, 'glucose-6-phosphate', dehydrogenase, 'deficiency,']), verbo([has]), complemento([raised, significant, concerns, due, to, its, hemolytic, activity])]). relacion([sujeto(['Future', studies, should, focus, on, effective, 'single-dose', molecules, that, can]), verbo([act]), complemento([against, all, stages, of, malaria, in, order, to, prevent, transmission])]). relacion([sujeto(['Newer', medicines]), verbo([have]), complemento([also, raised, concerns, in, terms, of, efficacy, and, safety])]). relacion([sujeto(['Treatment', strategies, that]), verbo([target]), complemento([the, blood, stage, with, 'transmission-blocking', properties, are, needed, to, prevent, future, drug, resistance])]). relacion([sujeto(['While', physical, activity]), verbo([has]), complemento([been, shown, to, improve, cognitive, performance, and, 'well-being,', office, workers, are, essentially, sedentary])]). relacion([sujeto(['Both', 'ONE', and, 'MICRO']), verbo([increased]), complemento(['self-perceived', energy, and, vigor, compared, to, 'SIT', '(', p, &, 'lt;', 0.05, for, 'all)'])]). relacion([sujeto(['MICRO,', but, not, 'ONE,', improved, 'mood,']), verbo([decreased]), complemento([levels, of, fatigue, and, reduced, food, cravings, at, the, end, of, the, day, compared, to, 'SIT', '(', p, &, 'lt;', 0.05, for, 'all)'])]). relacion([sujeto(['In', addition, to, the, beneficial, impact, of, physical, activity, on, levels, of, energy, and, 'vigor,', spreading, out, physical, activity, throughout, the, day, improved, 'mood,']), verbo([decreased]), complemento([feelings, of, fatigue, and, affected, appetite])]). relacion([sujeto(['This']), verbo([report]), complemento([describes, the, first, case, of, failure, of, 'dihydroartemisinin-piperaquine', '(', 'DHA-PPQ)', for, the, treatment, of, 'P'])]). relacion([sujeto(['Thus,', identifying, new, drug]), verbo([targets]), complemento([is, urgently, needed])]). relacion([sujeto(['Helicases', play, key, roles, in, a, wide, range, of, cellular, activities]), verbo([involving]), complemento(['DNA', and, 'RNA', 'transactions,', making, them, attractive, 'anti-malarial', drug, targets])]). relacion([sujeto(['ATP-dependent', 'DNA', helicase, gene, '(', 'PfRuvB3)', of, 'Plasmodium', falciparum, strain, 'K1,', a, chloroquine, and, 'pyrimethamine-resistant', 'strain,', was, inserted, into, 'pQE-TriSystem', 'His-Strep', 2, 'vector,', heterologously]), verbo([expressed]), complemento([and, affinity, purified])]). relacion([sujeto(['Helicase', and, 'ATPase', activities, were, characterized, as, well, as, 'co-factors']), verbo([required]), complemento([for, optimal, function])]). relacion([sujeto(['Recombinant', 'PfRuvB3']), verbo([has]), complemento([molecular, size, of, 59, &, 'nbsp;kDa,', showing, both, 'DNA', helicase, and, 'ATPase', activities])]). relacion([sujeto(['Its', helicase, activity, is, dependent, on, divalent, cations, '(', 'Cu(2+),', 'Mg(2+),', 'Ni(+2)', or, 'Zn(+2))', and, 'ATP', or, dATP, but, is]), verbo([inhibited]), complemento([by, high, 'NaCl', concentration, '(', &, 'gt;100 mM)'])]). relacion([sujeto(['PfPuvB3', is, unable, to]), verbo([act]), complemento([on, 'blunt-ended', duplex, 'DNA,', but, manifests, 'ATPase', activity, in, the, presence, of, either, 'single-', or, 'double-stranded', 'DNA'])]). relacion([sujeto([is]), verbo([inhibited]), complemento([by, 'doxorubicin,', daunorubicin, and, 'netropsin,', known, 'DNA', helicase, inhibitors])]). relacion([sujeto(['Differences', in, properties, of, 'RuvB', between, the, malaria, parasite, obtained, from, the, study, and, human, host]), verbo([provide]), complemento([an, avenue, leading, to, the, development, of, novel, drugs, targeting, specifically, the, malaria, form, of, 'RuvB', family, of, 'DNA', helicases])]). relacion([sujeto(['Existing', studies]), verbo([report]), complemento([a, positive, association, between, inadequate, health, literacy, and, 'immigrant\'s', adverse, health, outcomes])]). relacion([sujeto(['Findings', revealed, that, 71, &, 'nbsp;%', of, 'Somali', women, in, 'Oslo', lack, the, ability, to, 'obtain,', understand, and]), verbo([act]), complemento([upon, health, information, and, 'services,', and, to, make, appropriate, health, decisions])]). relacion([sujeto(['Enhanced', health, literacy, will, most, likely]), verbo([increase]), complemento([the, chance, to, better, health, outcomes, for, 'immigrants,', thereby, moving, towards, health, equity, in, the, 'Norwegian', society])]). relacion([sujeto(['Therefore,', policies, and, programs, are]), verbo([required]), complemento([to, focus, and, improve, health, literacy, of, immigrant, communities])]). relacion([sujeto(['Expression', of, homeotic, 'genes,', in, 'turn,', is, partially]), verbo([regulated]), complemento([by, insulator, binding, proteins, '(', 'IBPs)'])]). relacion([sujeto(['While', only, a, few, enhancer, blocking, 'IBPs']), verbo([have]), complemento([been, identified, in, 'vertebrates,', the, common, fruit, fly, 'Drosophila', melanogaster, harbors, at, least, twelve, different, enhancer, blocking, 'IBPs'])]). relacion([sujeto(['Furthermore', we]), verbo([found]), complemento(['GAF', orthologs, in, early, branching, insect, 'orders,', including, 'Zygentoma', '(', silverfish, and, 'firebrats)', and, 'Diplura', '(', 'two-pronged', 'bristletails)'])]). relacion([sujeto(['Our', results]), verbo([suggest]), complemento([that, a, substantial, number, of, 'IBPs', either, 'pre-date', the, evolution, of, insects, or, evolved, early, during, insect, evolution])]). relacion([sujeto(['This']), verbo([suggests]), complemento([an, evolutionary, history, of, insulator, binding, proteins, in, insects, different, to, that, previously, thought])]). relacion([sujeto(['Criminal', cases]), verbo([involving]), complemento([human, immunodeficiency, virus, transmission, or, exposure, require, that, courts, correctly, comprehend, the, rapidly, evolving, science, of, 'HIV', transmission, and, the, impact, of, an, 'HIV', diagnosis])]). relacion([sujeto(['This', consensus, 'statement,', written, by]), verbo([leading]), complemento(['HIV', clinicians, and, 'scientists,', provides, current, scientific, evidence, to, facilitate, just, outcomes, in, 'Australian', criminal, cases, involving, 'HIV'])]). relacion([sujeto(['The', use, of, phylogenetic, analysis, in, cases, of, suspected, 'HIV', transmission]), verbo([requires]), complemento([careful, consideration, of, its, limited, probative, value, as, evidence, of, causation, of, 'HIV', 'infection,', although, such, an, approach, may, provide, valuable, 'information,', particularly, in, relation, to, excluding, 'HIV', transmission, between, individuals])]). relacion([sujeto(['Most', people, recently, infected, with, 'HIV', are, able, to, commence, simple, treatment]), verbo([providing]), complemento([them, a, normal, and, healthy, life, 'expectancy,', largely, comparable, with, their, 'HIV-negative', peers])]). relacion([sujeto(['Among', people, who]), verbo([have]), complemento([been, diagnosed, and, are, receiving, 'treatment,', 'HIV', is, rarely, life, threatening])]). relacion([sujeto(['Changes', in, management, as, result, of, the, consensus, 'statement:', 'Given', the, limited, risk, of, 'HIV', transmission, per, sexual]), verbo([act]), complemento([and, the, limited, long, term, harms, experienced, by, most, people, recently, diagnosed, with, 'HIV,', appropriate, care, should, be, taken, before, 'HIV', prosecutions, are, pursued])]). relacion([sujeto(['There', is, no, convincing, evidence, that, classic, 'Lyme', disease, occurs, in, 'Australia,', nor, is, there, evidence, that, the, causative, 'agent,', 'Borrelia', 'burgdorferi,', is]), verbo([found]), complemento([in, 'Australian', animals, or, ticks])]). relacion([sujeto(['Antibiotic', therapy, for, chronic, &, 'quot;Lyme', 'disease-like', 'illness"', can]), verbo([cause]), complemento([harm, to, both, the, individual, '(', 'eg,', 'cannula-related', intravenous, 'sepsis)', and, the, broader, community, '(', increased, antimicrobial, resistance, 'rates)'])]). relacion([sujeto(['Until', there, is, strong, evidence, from, well, performed, clinical, studies, that, bacteria, present, in, 'Australia']), verbo([cause]), complemento([a, chronic, debilitating, illness, that, responds, to, prolonged, 'antibiotics,', treating, patients, with, &, 'quot;Lyme', 'disease-like', 'illness"', with, prolonged, antibiotic, therapy, is, 'unjustified,', and, is, likely, to, do, much, more, harm, than, good])]). relacion([sujeto(['β-synuclein', '(', 'βS),', a, presynaptic, protein, that, 'co-localizes', with, αS]), verbo([has]), complemento([been, recently, reported, to, act, as, an, inhibitor, of, αS, 'self-assembly'])]). relacion([sujeto(['We', also, carried, out, umbrella, samplings]), verbo([involving]), complemento([two, degrees, of, freedom, '(', one, being, the, distance, between, the, monomeric, units, and, the, other, angle, between, the, long, axes, of, the, two, monomeric, 'chains)', and, observed, similar, 'PMF', profile])]). relacion([sujeto(['So', our, findings]), verbo([suggest]), complemento([that, αS, readily, combines, with, βS, to, form, 'hetero-dimer', than, combining, with, itself, in, forming, 'homo-dimer'])]). relacion([sujeto(['The', objectives, of, this, study, are, to, examine, and]), verbo([report]), complemento([the, patterns, of, 'PA/ST', among, adolescents, in, 'East', 'London', living, in, superdiverse, 'communities,', to, identify, 'opportunities/barriers', to, 'PA', and, inform, 'policy/practice'])]). relacion([sujeto(['Obese', participants, were, less, likely, to]), verbo([report]), complemento([engaging, in, 'PA', five, times, in, the, past, week, '(', 'U', =, 4.11, ',', z, =, -, 1.17, ',', p, &, 'lt;'])]). relacion([sujeto([5, ')', were, significantly, more, likely, to]), verbo([report]), complemento([engaging, in, no, activity])]). relacion([sujeto(['Walking', '(', 36.4, '%', ')', ',', 'jogging/running', '(', 29.9, '%', ')', ',', and, football, '(', 28, '%', ')', were, the, most, frequently]), verbo([reported]), complemento([activities])]). relacion([sujeto(['Engaging', girls, in, 'PA', during, and, after, school, is, important, and, making, sports, clubs, and, activities, available, and, attractive, to, this]), verbo([target]), complemento([group, may, help, increase, engagement, in, 'PA', and, reduce, 'ST'])]). relacion([sujeto(['Findings', support, the, need, for, more, 'sex-specific', and, culturally, responsive, pedagogy, in, schools, with, curricula, that, respects, diversity, and, individuality, and]), verbo([has]), complemento([meaning, and, value, amongst, superdiverse, young, people])]). relacion([sujeto(['Finally,', we, need, to, extend, current, work, presented, and]), verbo([provide]), complemento([substantial, evidence, of, the, ways, young, people, from, minority, ethnic, groups, process, and, act, on, the, public, health, policy, and, the, ways, they, understand, and, enact, 'PA'])]). relacion([sujeto(['The', porous, 'MoO3-CoMoO4', microspheres, are, constructed, by, homogeneously, dispersed, 'MoO3', and, 'CoMoO4', subunits, and, their, 'lithiation/delithiation', processes, were, studied, by, ex, situ, 'TEM', to]), verbo([reveal]), complemento([the, mechanism, of, the, reversible, conversion, reaction])]). relacion([sujeto(['Co', nanoparticles, are, in, situ, formed, from, 'CoMoO4', during, the, lithiation, 'process,', which, then]), verbo([act]), complemento([as, the, catalyst, to, guarantee, the, reversible, decomposition, of, 'Li2O,', thus, effectively, improving, the, reversible, specific, capacity, and, initial, 'Coulombic', efficiency])]). relacion([sujeto(['Moreover,', the, pores, in, 'MoO3-CoMoO4', microspheres, also, greatly]), verbo([enhance]), complemento([their, mechanical, strength, and, provide, enough, cavity, to, alleviate, volume, changes, during, repeated, cycling])]). relacion([sujeto(['This', work]), verbo([provides]), complemento([impetus, for, further, development, in, electrochemical, charge, storage, devices])]). relacion([sujeto(['Both', '(', -, ')', -, sesamin, doses, reduced]), verbo([decreases]), complemento([in, the, retention, latency, time, in, the, passive, avoidance, 'test,', latency, to, fall, of, rotarod, test, and, distance, traveled, in, the, open, field, 'test,', and, attenuated, decreases, in, tyrosine, hydroxylase, '(', 'TH)-immunopositive', 'cells,', 'dopamine,', and, its, metabolites, in, the, substantia, 'nigra-striatum'])]). relacion([sujeto(['(', -, ')', -, 'Sesamin', reduced]), verbo([increases]), complemento([in, the, retention, transfer, latency, time, in, the, elevated, 'plus-maze', test, and, 'N-methyl-d-aspartate', receptor, '(', 'NMDAR)', expression, and, reduced, decreases, in, the, phosphorylation, of, extracellular, 'signal-regulated', kinase, '(', 'ERK1/2)', and, cyclic, 'AMP-response', element, binding, protein, '(', 'CREB)', in, the, hippocampus])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, '(', -, ')', -, sesamin, protects, against, habit, learning, memory, deficits, by, activating, the, dopamine, neuronal, 'system,', while, spatial, memory, deficits, are, decreased, by, its, modulatory, effects, on, the, 'NMDAR-ERK1/2-CREB', system])]). relacion([sujeto(['Accordingly,', '(', -, ')', -, sesamin, may]), verbo([act]), complemento([as, an, adjuvant, phytonutrient, for, motor, and, memory, deficits, in, patients, with, 'PD', receiving, 'l-DOPA'])]). relacion([sujeto(['Hepatocytes', are]), verbo([involved]), complemento([in, the, endogenous, and, drug, 'metabolism;', many, of, the, enzymes, involved, in, those, processes, are, incorporated, into, extracellular, vesicles, and, secreted, into, the, bloodstream])]). relacion([sujeto(['Drug-induced', liver, damage]), verbo([increases]), complemento([the, number, of, circulating, extracellular, vesicles, and, affects, the, release, and, content, of, 'hepatocyte-derived', vesicles])]). relacion([sujeto(['We', performed, a]), verbo([targeted]), complemento(['ultra-high', performance, liquid, 'chromatography-mass', spectrometry, '(', 'UHPLC-MS)', metabolomics, analysis, of, serum, samples])]). relacion([sujeto(['These', compounds, are, the, components, of, biological, 'membranes;', our, observations]), verbo([suggest]), complemento([that, the, vesicles, might, take, part, in, remodelling, and, maintenance, of, the, membranes])]). relacion([sujeto(['Alterations', in, the, levels, of, some, other, serum, metabolites, might]), verbo([have]), complemento([deleterious, 'consequences,', for, 'example,', the, tetracosanoic, acid, with, its, cardiovascular, effects])]). relacion([sujeto(['However,', some, of, the, metabolites, whose, levels, were, 'increased,', including, 'alpha-linoleic', and, tauroursodeoxycholic, 'acids,']), verbo([have]), complemento([been, reported, to, have, a, protective, effect])]). relacion([sujeto(['Our']), verbo([targeted]), complemento([metabolomics, analysis, indicated, that, the, hepatic, extracellular, vesicles, act, as, 'nano-metabolic', machines, supplying, the, extracellular, environment, with, the, means, to, integrate, diverse, tissue, responses])]). relacion([sujeto(['Multidirectional', interactions, among, the, 'immune,', 'endocrine,', and, nervous, systems]), verbo([have]), complemento([been, demonstrated, in, humans, and, 'non-human', animal, models, for, many, decades, by, the, biomedical, 'community,', but, ecological, and, evolutionary, perspectives, are, lacking])]). relacion([sujeto(['Behavior', can, exert, profound, influences, on, these, 'phenotypes,', which, can, in, turn, reciprocally]), verbo([modulate]), complemento([behavior])]). relacion([sujeto(['One', classic, example, is, the, immunocompetence, handicap, hypothesis, '(', 'ICHH),', which, proposes, that, steroid, hormones]), verbo([act]), complemento([as, mediators, of, traits, important, for, female, choice, while, suppressing, the, immune, system])]). relacion([sujeto(['Reciprocally,', 'neuroendocrine-immune', pathways, can]), verbo([promote]), complemento([the, development, of, altered, behavioral, 'states,', such, as, sickness, behavior])]). relacion([sujeto(['Understanding', the, energetic, signals, that]), verbo([mediate]), complemento(['neuroendocrine-immune', crosstalk, is, an, active, area, of, research])]). relacion([sujeto(['Although', the, field, of, psychoneuroimmunology, '(', 'PNI)']), verbo([has]), complemento([begun, to, explore, this, crosstalk, from, a, biomedical, 'standpoint,', the, 'neuroendocrine-immune-behavior', nexus, has, been, relatively, underappreciated, in, comparative, species])]). relacion([sujeto(['The', field, of, 'ecoimmunology,', while, traditionally, emphasizing, the, study, of, 'non-model', systems, from, an, ecological, evolutionary, 'perspective,', often, under, natural, 'conditions,']), verbo([has]), complemento([focused, less, on, the, physiological, mechanisms, underlying, behavioral, responses])]). relacion([sujeto(['This']), verbo([requires]), complemento([examining, lineages, that, are, still, in, the, process, of, divergence, or, incipient, species])]). relacion([sujeto(['Behavioral', isolation, did, not]), verbo([have]), complemento([any, profound, effect, on, preventing, gene, flow])]). relacion([sujeto(['We']), verbo([found]), complemento([evidence, for, differences, in, genital, morphology, that, may, contribute, to, failed, insemination, attempts, during, copulation])]). relacion([sujeto(['Our', results]), verbo([provide]), complemento([evidence, for, the, contribution, of, several, 'postmating-prezygotic', barriers, that, predate, behavioral, isolation, and, act, as, primary, inhibitors, of, gene, flow, in, this, system])]). relacion([sujeto(['This', is, a, 'surprising,', yet, perhaps, often, overlooked, feature, of, barriers]), verbo([acting]), complemento([early, in, sympatric, speciation, process])]). relacion([sujeto(['The', present, study, aimed, to, investigate, the, effects, of, berberine, '(', 'BRB)', on, spatial, and, learning, 'memory,', 'anxiety,', acetylcholinesterase, activity, and, cell, death, in, an, experimental, model, of, intracerebroventricular, streptozotocin, '(', 'ICV-STZ)']), verbo([induced]), complemento([sporadic, 'Alzheimer\'s-like', dementia])]). relacion([sujeto(['Administration', of, 'BRB']), verbo([prevented]), complemento([the, memory, 'loss,', anxiogenic, 'behavior,', increased, acetylcholinesterase, activity, and, cell, death, induced, by, 'ICV-STZ'])]). relacion([sujeto(['This', may, be, 'explained,', in, 'part,', by, a, protective, effect, of, 'BRB', on, ameliorating, the, progression, of, neurodegenerative, 'diseases,', including, 'Alzheimer\'s', 'disease,', and, the, results, of, this, study]), verbo([provide]), complemento([a, better, understanding, of, the, effect, of, 'BRB', on, the, brain])]). relacion([sujeto(['Thus,', 'BRB', may]), verbo([act]), complemento([as, a, potential, neuroprotective, agent])]). relacion([sujeto(['Multiple', studies]), verbo([have]), complemento([indicated, a, strong, correlation, between, these, two, diseases])]). relacion([sujeto(['Although', amylin, aggregation]), verbo([has]), complemento([been, demonstrated, to, induce, cytotoxicity, in, neurons, through, altering, 'Ca(2+)', 'homeostasis,', the, underlying, mechanisms, have, not, been, fully, explored])]). relacion([sujeto(['We', demonstrated, that, the, amylin, receptor, antagonist, 'AC187', abolished, the, 'Ca(2+)', response]), verbo([induced]), complemento([by, low, concentrations, of, human, amylin, '(', 'hAmylin)'])]). relacion([sujeto(['However,', the, 'Ca(2+)', response]), verbo([induced]), complemento([by, higher, concentrations, of, hAmylin, was, independent, of, the, amylin, receptor])]). relacion([sujeto(['Moreover,', application, of, the, transient, receptor, potential, '(', 'TRP)', channel, antagonist, ruthenium, red, '(', 'RR)', attenuated, the, 'hAmylin-induced']), verbo([increase]), complemento([in, 'Ca(2+)'])]). relacion([sujeto(['Single-cell', 'RT-PCR', demonstrated, that, transient, receptor, potential, vanilloid, 4, '(', 'TRPV4)', mRNA, was]), verbo([expressed]), complemento([in, most, of, the, 'hAmylin-responsive', neurons])]). relacion([sujeto(['In', 'addition,', selective, knockdown, of, 'TRPV4', channels]), verbo([inhibited]), complemento([the, 'hAmylin-evoked', 'Ca(2+)', response])]). relacion([sujeto(['These', results, indicated, that, different, concentrations, of, hAmylin]), verbo([act]), complemento([through, different, pathways])]). relacion([sujeto(['The', amylin, receptor]), verbo([mediates]), complemento([the, excitatory, effects, of, low, concentrations, of, hAmylin])]). relacion([sujeto(['In', 'contrast,', for, high, concentrations, of, 'hAmylin,', hAmylin, aggregates, precipitated, on, the, neuronal, 'membrane,']), verbo([activated]), complemento(['TRPV4', channels, and, subsequently, triggered, membrane, 'voltage-gated', calcium, channel, opening, followed, by, membrane, depolarization])]). relacion([sujeto(['Therefore,', our, data]), verbo([suggest]), complemento([that, 'TRPV4', is, a, key, molecular, mediator, for, the, cytotoxic, effects, of, hAmylin, on, hippocampal, neurons])]). relacion([sujeto(['YopJ', is, a, cysteine, protease, and, can]), verbo([act]), complemento([as, a, deubiquitinating, enzyme, that, deubiquitinates, several, targets, in, multiple, signaling, pathways])]). relacion([sujeto(['Our', studies, demonstrate, that, 'YopJ']), verbo([targets]), complemento(['STING', to, inhibit, 'IRF3', signaling])]). relacion([sujeto(['Specially,', 'YopJ']), verbo([interacts]), complemento([with, 'STING', to, block, its, 'ER-to-Golgi', traffic, and, remove, its, 'K63-linked', ubiquitination, chains])]). relacion([sujeto(['The', 172, th, cysteine, of, 'YopJ']), verbo([mediated]), complemento(['STING', deubiquitination, and, 'IRF3', signaling, inhibition])]). relacion([sujeto(['Consequently,', mice, infected, with, 'WT', and, 'ΔYopJ/YopJ', bacteria]), verbo([induced]), complemento([lower, levels, of, 'IRF3', and, 'IFN-β,', decreased, inflammation, and, reduced, staining, of, 'STING', as, compared, to, 'ΔYopJ', and, 'ΔYopJ/YopJ', 'C172A', strains, infection])]). relacion([sujeto(['The', data, herein]), verbo([reveal]), complemento([a, previously, unrecognized, mechanism, by, which, 'YopJ', modulates, innate, immune, signaling])]). relacion([sujeto(['This', study, aimed, to, determine, whether, gravid, female, locusts, can, discriminate, among, substrates, of]), verbo([increasing]), complemento([salinity, '(', 0, ',', 4, ',', 8, ',', 12, ',', 16, ',', 20, ',', 24, ',', and, 28, ppt, 'NaCl)', when, attempting, 'oviposition,', and, quantify, the, effects, of, saline, substrate, on, direct, developing, egg, 'viability,', and, subsequent, hatchling, nymph, body, weight, and, survival])]). relacion([sujeto(['Gravid', female, locusts, increasingly, excavated, and, withdrew, prior, to, completing, oviposition, in, substrates, of]), verbo([increasing]), complemento(['salinity,', but, similar, numbers, of, completed, egg, pods, were, observed, across, treatments])]). relacion([sujeto(['Egg', weight, at, 50, '%', total, development, time, and, successful, egg, development, to, nymph, emergence]), verbo([decreased]), complemento([with, increasing, substrate, salinity])]). relacion([sujeto(['Hatchling', nymph, body, weight, and, survival, to, second, instar, also]), verbo([decreased]), complemento([with, increasing, substrate, salinity])]). relacion([sujeto(['In', contrast, to, common, trivalent, boron, 'compounds,', the, 'boron-based', ligands, in, this, study]), verbo([act]), complemento([as, 'electron-donating', ligands])]). relacion([sujeto(['The']), verbo([reported]), complemento([iron, hydride, complexes, exhibit, a, unique, reactivity, 'pattern,', undergoing, a, reversible, 'B-H', reductive, elimination, concomitant, with, oxidation, of, the, 'boron(I)', center])]). relacion([sujeto(['Bordetella', 'pertussis,', the, causative, agent, of, whooping, 'cough,', secretes, and]), verbo([releases]), complemento([adenylate, cyclase, toxin, '(', 'ACT),', which, is, a, protein, bacterial, toxin, that, targets, host, cells, and, disarms, immune, defenses])]). relacion([sujeto(['ACT']), verbo([binds]), complemento([filamentous, haemagglutinin, '(', 'FHA),', a, 'surface-displayed', 'adhesin,', and, until, 'now,', the, consequences, of, this, interaction, were, unknown])]). relacion([sujeto([bronchiseptica, mutant, lacking, 'ACT', produced, more, biofilm, than, the, parental, 'strain;']), verbo([leading]), complemento(['Irie', et, al])]). relacion([sujeto(['Here', we, characterize, the, physical, interaction, of, 'ACT', with, 'FHA', and]), verbo([provide]), complemento([evidence, linking, that, interaction, to, inhibition, of, biofilm, in, vitro])]). relacion([sujeto(['Exogenous', 'ACT']), verbo([inhibits]), complemento([biofilm, formation, in, a, 'concentration-dependent', manner, and, the, 'N-terminal', catalytic, domain, of, 'ACT', '(', 'AC', 'domain)', is, necessary, and, sufficient, for, this, inhibitory, effect])]). relacion([sujeto(['AC', 'Domain']), verbo([interacts]), complemento([with, the, 'C-terminal', segment, of, 'FHA', with, '∼650', nM, affinity])]). relacion([sujeto(['ACT', does, not]), verbo([inhibit]), complemento([biofilm, formation, by, 'Bordetella', lacking, the, mature, 'C-terminal', domain, '(', 'MCD),', suggesting, the, direct, interaction, between, 'AC', domain, and, the, 'MCD', is, required, for, the, inhibitory, effect])]). relacion([sujeto(['Interleukin-2', inducible, 'T-cell', kinase, '(', 'ITK)', is]), verbo([expressed]), complemento([in, 'T', 'cells,', and, plays, an, important, role, in, autoimmune, inflammatory, diseases, through, regulating, the, balance, of, 'Th17/Treg'])]). relacion([sujeto(['These', data, indicate, that]), verbo([increased]), complemento(['ITK', expression, could, act, as, a, disease, activity, marker, and, as, a, risk, factor, for, involvement, in, 'SLE,', but, it, still, needs, further, study, to, confirm])]). relacion([sujeto(['Subjective', responses, to, meals, are, altered, by, shortened, sleep, time, and, anxiety, 'state,', but, this, effect]), verbo([has]), complemento([been, poorly, studied, in, shift, workers, -, who, act, as, a, typical, model, concerning, sleep, restriction, and, present, high, levels, of, anxiety])]). relacion([sujeto(['Linear', regression, indicated, 'that,', after, a, night, 'shift,', anxiety, scores, were, negatively]), verbo([associated]), complemento([with, hunger, before, breakfast, '(', 'p = 0'])]). relacion([sujeto(['It', is, concluded, that, night, shifts]), verbo([increase]), complemento([mean, hunger, and, anxiety, scores])]). relacion([sujeto(['Anxiety', levels, seem, to, interfere, with, the, responses]), verbo([associated]), complemento([with, food, consumption])]). relacion([sujeto(['The', subthalamic, nucleus, is, thought, to]), verbo([act]), complemento([as, a, behavioural, 'go/no-go', instance, by, means, of, oscillatory, communication, in, the, theta, band, with, the, prefrontal, cortex])]). relacion([sujeto(['Because', subthalamic, 'alpha-theta', frequency, stimulation]), verbo([has]), complemento([been, shown, to, exert, beneficial, effects, on, verbal, fluency, in, 'Parkinson\'s', 'disease,', we, hypothesized, that, an, 'alpha-theta', oscillatory, network, involving, the, subthalamic, nucleus, underlies, verbal, generation, task, performance, as, a, gating, instance, for, speech, execution])]). relacion([sujeto(['Time-frequency', analysis, revealed, a, significant, 'alpha-theta', power]), verbo([increase]), complemento([and, enhanced, 'alpha-theta', coherence, between, the, subthalamic, nucleus, and, the, frontal, surface, 'EEG', during, the, verbal, generation, task])]). relacion([sujeto(['Beta', and, gamma, oscillations, were, not, significantly]), verbo([modulated]), complemento([by, the, task])]). relacion([sujeto(['Power']), verbo([increase]), complemento([significantly, correlated, with, verbal, generation, performance])]). relacion([sujeto(['Our', results]), verbo([provide]), complemento([experimental, evidence, for, local, 'alpha-theta', oscillatory, activity, in, the, subthalamic, nucleus, and, coherence, to, frontal, associative, areas, as, a, neurophysiological, mechanism, underlying, a, verbal, generation, task])]). relacion([sujeto(['Alpha-theta', oscillations, can, be, interpreted, as, the, rhythmic, gating, signature, in, a, speech]), verbo([executing]), complemento(['subthalamic-prefrontal', network])]). relacion([sujeto(['Homozygous', or, compound, heterozygous, mutations, in, 'DHCR7']), verbo([lead]), complemento([to, the, developmental, disease, 'Smith-Lemli-Opitz', 'syndrome,', which, can, also, result, in, fetal, 'mortality,', highlighting, the, importance, of, this, enzyme, in, human, development, and, survival])]). relacion([sujeto(['Thus,', 'DHCR7', exerts, complex, biological, 'effects,']), verbo([involved]), complemento([in, both, cholesterol, and, vitamin, 'D', production])]). relacion([sujeto(['Indeed,', we, argue, that, 'DHCR7', can]), verbo([act]), complemento([as, a, switch, between, cholesterol, and, vitamin, 'D', synthesis])]). relacion([sujeto(['Greater', understanding, about, 'DHCR7', 'function,', regulation, and, its, place, within, cellular, metabolism, will]), verbo([provide]), complemento([important, insights, into, its, biological, roles])]). relacion([sujeto(['Exogenous', ciliary, neurotrophic, factor, '(', 'CNTF)', administration]), verbo([promotes]), complemento([the, survival, of, motor, neurons, in, a, wide, range, of, models])]). relacion([sujeto(['It', also]), verbo([increases]), complemento([the, expression, of, the, critical, neurotransmitter, 'enzyme,', choline, acetyltransferase, '(', 'ChAT),', by, in, vitro, motor, 'neurons,', likely, independent, of, its, effects, on, their, survival])]). relacion([sujeto(['We']), verbo([have]), complemento([used, the, adult, mouse, facial, nerve, crush, model, and, adult, onset, conditional, disruption, of, the, 'CNTF', receptor, α, '(', 'CNTFRα)', gene, to, directly, examine, the, in, vivo, roles, played, by, endogenous, 'CNTF', receptors, in, adult, motor, neuron, survival, and, 'ChAT', 'maintenance,', independent, of, developmental, functions])]). relacion([sujeto(['We']), verbo([have]), complemento([previously, shown, that, adult, activation, of, the, 'CreER', gene, construct, in, floxed, 'CNTFRα', mice, depletes, this, essential, receptor, subunit, in, a, large, subset, of, motor, neurons, '(', and, all, skeletal, 'muscle,', as, shown, 'here)', but, has, no, effect, on, the, survival, of, intact, or, lesioned, motor, 'neurons,', thereby, indicating, that, these, adult, 'CNTF', receptors, play, no, essential, survival, role, in, this, 'model,', in, contrast, to, their, essential, role, during, embryonic, development])]). relacion([sujeto(['We', show, here, that, this, same, 'CNTFRα', depletion, does, not, affect, 'ChAT', labeling, in, 'non-lesioned', motor, 'neurons,', but, it, significantly]), verbo([increases]), complemento([the, loss, of, 'ChAT', following, nerve, crush])]). relacion([sujeto(['The', data]), verbo([suggest]), complemento([that, while, neither, motor, neuron, nor, muscle, 'CNTF', receptors, play, a, 'significant,', 'non-redundant', role, in, the, maintenance, of, 'ChAT', in, intact, adult, motor, 'neurons,', the, receptors, become, essential, for, 'ChAT', maintenance, when, the, motor, neurons, are, challenged, by, nerve, crush])]). relacion([sujeto(['Therefore,', the, data]), verbo([suggest]), complemento([that, the, receptors, act, as, a, critical, component, of, an, endogenous, neuroprotective, mechanism])]). relacion([sujeto(['The', existence, of, hard, tissue, pulleys, that]), verbo([act]), complemento([to, change, the, direction, of, a, muscle, insertion, tendon, is, well, known, in, the, human, body])]). relacion([sujeto(['Our', recent, studies]), verbo([have]), complemento([shown, that, the, development, of, pulleys, 'Nos'])]). relacion([sujeto(['Bath', perfusion, of, 'PPB', reduced, the, 'fast-inactivating', sodium, current, '(', 'INa)', 'amplitude,']), verbo([causing]), complemento([a, hyperpolarizing, shift, in, the, inactivation, curve, of, the, 'INa,', and, markedly, delayed, the, sodium, channel, recovery, from, the, inactivation, state])]). relacion([sujeto(['Also,', 'PPB', effectively]), verbo([suppressed]), complemento([the, 'riluzole-sensitive,', persistent, sodium, current, '(', 'INaP)'])]). relacion([sujeto(['PPB', perfusion, also, modified, the, action, potential, 'kinetics,', and, higher, concentrations, of, 'PPB']), verbo([suppressed]), complemento([the, spike, activity])]). relacion([sujeto(['These', results, indicate, that, 'PPB', reduces, the, excitability, of, 'CA1', pyramidal, neurons, by]), verbo([modulating]), complemento(['voltage-dependent', sodium, channels])]). relacion([sujeto(['Our', results, indicate, that, similar, to, local, anesthetics, and, anticonvulsant, drugs, that]), verbo([act]), complemento([on, sodium, 'channels,', 'PPB', acts, in, a, 'use-dependent', manner])]). relacion([sujeto([the, 'oxysterome)']), verbo([involved]), complemento([in, a, plethora, of, physiological, processes])]). relacion([sujeto(['They', can]), verbo([act]), complemento([through, 'GPCR', '(', e])]). relacion([sujeto(['EBI2,', 'SMO,', 'CXCR2),']), verbo([nuclear]), complemento([receptors, '(', 'LXR,', 'ROR,', 'ERα)', and, through, transporters, or, regulatory, proteins])]). relacion([sujeto(['Additionally,', they, were, shown, to, be]), verbo([involved]), complemento([in, other, processes, such, as, immune, regulatory, functions, and, brain, homeostasis])]). relacion([sujeto(['In', this, 'review,', we, discuss, the, complex, metabolism, and, molecular]), verbo([targets]), complemento(['(', including, binding, 'properties)', of, these, bioactive, lipids, in, human, and, mice])]). relacion([sujeto(['We', also, summarize, the, levels, of, oxysterols]), verbo([reported]), complemento([in, two, key, organs, in, oxysterol, metabolism, '(', liver, and, 'brain),', plasma, and, cerebrospinal, fluid])]). relacion([sujeto(['Finally,', we, consider, future, opportunities, and, directions, in, the, oxysterol, field, in, order, to]), verbo([gain]), complemento([a, better, insight, and, understanding, of, the, complex, oxysterol, system])]). relacion([sujeto(['Internationally,', there, is]), verbo([increasing]), complemento([recognition, of, the, importance, of, multilevel, policies, and, actions, that, address, healthy, and, environmentally, friendly, food, behaviours])]). relacion([sujeto(['To', this, 'end,', we, undertook, a, qualitative, study, to, assess, consumer, 'perceptions,', experiences, and, attitudes, towards, healthy, and, environmentally, friendly, foods, and, four]), verbo([target]), complemento(['behaviours:', reducing, overconsumption, of, food, beyond, energy, 'needs,', reducing, consumption, of, 'low-nutrient', energy, dense, 'foods,', eating, less, 'animal-', and, more, 'plant-derived', 'foods,', and, reducing, food, waste])]). relacion([sujeto(['The', four]), verbo([target]), complemento([food, behaviours, were, primarily, associated, and, motivated, by, an, impact, on, 'health,', except, for, not, wasting, foods])]). relacion([sujeto(['Overall,', consumers]), verbo([found]), complemento([a, joined, concept, of, healthy, and, environmentally, friendly, foods, an, acceptable, idea])]). relacion([sujeto(['We', recommend, that, health, should, remain, the, overarching, principle, for, policies, and, actions, concerned, with, shifting, consumer, 'behaviours,', as, this, personal, benefit, appears, to]), verbo([have]), complemento([a, greater, potential, to, support, behaviour, change])]). relacion([sujeto(['Future', consumer, focused, work, could, pay, attention, to, framing, behavioural, 'messages,']), verbo([providing]), complemento([intermediate, behavioural, 'goals,', and, a, multiple, target, approach, to, change, habitual, behaviours])]). relacion([sujeto(['The', recent]), verbo([finding]), complemento([that, hydropersulfides, '(', 'RSSH)', are, biologically, prevalent, in, mammalian, systems, has, prompted, further, investigation, of, their, chemical, properties, in, order, to, provide, a, basis, for, understanding, their, potential, 'functions,', if, any])]). relacion([sujeto(['Hydropersulfides']), verbo([have]), complemento([been, touted, as, 'hyper-reactive', 'thiol-like', species, that, possess, increased, nucleophilicity, and, reducing, capabilities, compared, to, their, thiol, counterparts])]). relacion([sujeto(['Herein,', using, persulfide, generating, model, 'systems,', the, ability, of, 'RSSH', species, to]), verbo([act]), complemento([as, 'one-electron', reductants, has, been, examined])]). relacion([sujeto(['Somewhat', 'surprisingly,', 'however,', 'RSS·', was]), verbo([found]), complemento([to, be, stable, in, the, presence, of, both, 'O2', and, 'NO', and, only, appears, to, dimerize])]). relacion([sujeto(['Pluripotent', stem, cells]), verbo([act]), complemento([as, an, excellent, cell, source, for, disease, therapy, because, of, its, specific, characteristics, of, 'self-renewal', and, differentiation])]). relacion([sujeto(['However,', the, strategies, and, mechanisms, of]), verbo([maintaining]), complemento([naive, pluripotent, stem, cells, remain, unclear])]). relacion([sujeto(['In', this, 'study,', we]), verbo([found]), complemento([that, folic, acid, '(', 'FA)', sustained, mouse, embryonic, stem, cell, '(', 'ESC)', pluripotency, and, enabled, 'long-term', maintenance, of, the, naive, state, of, 'ESCs', under, 'CHIR99021', conditions])]). relacion([sujeto(['Mechanistic', experiments, showed, that, 'STAT3', pathway, partially]), verbo([mediated]), complemento([the, effect, of, 'FA', after, which, the, interaction, between, 'STAT3', and, importin, α5, was, enhanced])]). relacion([sujeto(['Meanwhile,', 'MEK/ERK', signaling, also]), verbo([acted]), complemento([downstream, of, 'FA', in, maintaining, 'ESC', pluripotency])]). relacion([sujeto(['Furthermore,', 'FA', significantly]), verbo([promoted]), complemento([mouse, somatic, cell, reprogramming])]). relacion([sujeto(['Overall,', our, study, identified, an, effective, chemical, condition, for]), verbo([maintaining]), complemento([homogeneous, 'ESCs', and, highlighted, the, important, roles, of, 'LIF/STAT3', and, 'MEK/ERK', signaling, in, naive, 'ESC', pluripotency])]). relacion([sujeto(['Th17', cells, are, key, players, in, defense, against, pathogens, and]), verbo([maintaining]), complemento([tissue, 'homeostasis,', but, also, act, as, critical, drivers, of, autoimmune, diseases])]). relacion([sujeto(['Based', on, 'single-cell', 'RNA-seq', profiling, of, pathogenic, versus, nonpathogenic, 'Th17', 'cells,', we, identified, protein, 'C', receptor, '(', 'PROCR)', as, a, cell, surface, molecule]), verbo([expressed]), complemento([in, covariance, with, the, regulatory, module, of, 'Th17', cells])]). relacion([sujeto(['Although', 'PROCR', expression, in, 'T', cells, was, controlled, by, the, cooperative, action, of, the, 'Th17', 'lineage-specific', transcription, factors, 'RORγt,', 'IRF4,', and, 'STAT3,', 'PROCR', negatively]), verbo([regulated]), complemento(['Th17', differentiation])]). relacion([sujeto(['CD4(+)', 'T', cells, from, 'PROCR', low, expressor, mutant, mice, readily, differentiated, into, 'Th17', 'cells,', whereas, addition, of, the, 'PROCR', 'ligand,']), verbo([activated]), complemento([protein, 'C,', inhibited, 'Th17', differentiation, in, vitro])]). relacion([sujeto(['In', 'addition,', 'PROCR']), verbo([acted]), complemento([as, a, negative, regulator, of, 'Th17', pathogenicity, in, that, it, 'down-regulated', expression, of, several, pathogenic, signature, 'genes,', including, 'IL-1', and, 'IL-23', receptors])]). relacion([sujeto(['Furthermore,', 'T', 'cell-specific', deficiency, of, 'PROCR', resulted, in, the, exacerbation, of, experimental, autoimmune, encephalomyelitis, '(', 'EAE)', and, higher, frequencies, of, 'Th17', cell, in, 'vivo,', indicating, that, 'PROCR', also]), verbo([inhibits]), complemento([pathogenicity, of, 'Th17', cells, in, vivo])]). relacion([sujeto(['PROCR', thus, does, not, globally]), verbo([inhibit]), complemento(['Th17', responses, but, could, be, targeted, to, selectively, inhibit, proinflammatory, 'Th17', cells])]). relacion([sujeto(['The', upper, layer, of, the, membrane, was, comprised, by, hyaluronic, acid, and, polycaprolactone, in, order, to]), verbo([provide]), complemento([mechanical, support, and, also, to, act, as, a, physical, barrier, against, external, threats])]). relacion([sujeto(['Chitosan', and, zein, were, used, to, produce, the, bottom, layer, that, was, loaded, with, salicylic, 'acid,', in, order, to]), verbo([confer]), complemento(['anti-inflammatory', and, antimicrobial, activity, to, this, layer])]). relacion([sujeto(['The', physicochemical, properties, of, the, membranes, were, determined, and, the, obtained, results, showed, that, the, produced, electrospun, membrane, display, an, ideal, 'porosity,', appropriate, mechanical, 'properties,', controlled, water]), verbo([loss]), complemento([and, a, suitable, salicylic, acid, release, profile])]). relacion([sujeto(['In', 'conclusion,', the, gathered, data]), verbo([reveal]), complemento([that, this, electrospun, membrane, has, suitable, properties, to, be, used, as, a, wound, dressing])]). relacion([sujeto(['Cell', wall, fortification, is, one, of, the, best, resistance, mechanisms, in, wheat, against, 'Fusarium', graminearum, which]), verbo([causes]), complemento(['FHB'])]). relacion([sujeto(['Metabolomics', approach, in, our, study]), verbo([led]), complemento([to, the, identification, of, a, wide, array, of, 'resistance-related', '(', 'RR)', 'metabolites,', among, which, hydroxycinnamic, acid, amides, '(', 'HCAAs),', such, as, coumaroylagmatine, and, 'coumaroylputrescine,', were, the, highest, fold, change, 'RR', metabolites, in, the, rachis, of, a, resistant, 'near-isogenic', line, '(', 'NIL-R)', upon, 'F'])]). relacion([sujeto(['Placement', of, these, metabolites, in, the, secondary, metabolic, pathway]), verbo([led]), complemento([to, the, identification, of, a, gene, encoding, agmatine, coumaroyl, 'transferase,', herein, referred, to, as, 'TaACT,', as, a, candidate, gene])]). relacion([sujeto(['Phylogenetic', analysis]), verbo([suggested]), complemento([that, 'TaACT', shared, closest, phylogenetic, relationship, with, an, 'ACT', ortholog, in, barley])]). relacion([sujeto(['Sequence', analysis, of, 'TaACT', in, resistant, and, susceptible, 'NILs,', with, contrasting, levels, of, resistance, to, 'FHB,']), verbo([led]), complemento([to, the, identification, of, several, single, nucleotide, polymorphisms, '(', 'SNPs)', and, two, inversions, that, may, be, important, for, gene, function])]). relacion([sujeto(['Further,', a, role, for, 'TaACT', in, 'FHB', resistance, was, functionally, validated, by, 'virus-induced', gene, silencing, '(', 'VIGS)', in, wheat, 'NIL-R', and, based, on, complementation, studies, in, 'Arabidopsis', with]), verbo([act]), complemento([mutant, background])]). relacion([sujeto(['The', disease, 'severity,', fungal, biomass, and, 'RR', metabolite, analysis, confirmed, 'TaACT', as, an, important, gene, in, wheat, 'FHB', 'QTL-2DL,']), verbo([conferring]), complemento([resistance, to, 'F'])]). relacion([sujeto(['The', purpose, of, this, study, was, to, evaluate, themes, related, to, 'patients\'', experience, in, undergoing, 'mammography,', as]), verbo([expressed]), complemento([on, 'Twitter'])]). relacion([sujeto(['Identified', themes, included, breast, compression, '(', 24.4, '%', ')', ',', advising, other, patients, to, undergo, screening, '(', 23.9, '%', ')', ',', recognition, of, the, health, importance, of, the, examination, '(', 18.8, '%', ')', ',', the]), verbo([act]), complemento([of, waiting, '(', 10.1, '%', ')', ',', relief, regarding, results, '(', 9.7, '%', ')', ',', reflection, that, the, examination, was, not, that, bad, '(', 9.1, '%', ')', ',', generalized, apprehension, regarding, the, examination, '(', 8.2, '%', ')', ',', interactions, with, staff, '(', 8.0, '%', ')', ',', the, gown, '(', 5.0, '%', ')', ',', examination, costs, or, access, '(', 3.4, '%', ')', ',', offering, or, reaching, out, for, online, support, from, other, patients, '(', 3.2, '%', ')', ',', perception, of, screening, as, a, sign, of, aging, '(', 2.4, '%', ')', ',', and, the, waiting, room, or, waiting, room, amenities, '(', 1.3, '%', ')'])]). relacion([sujeto(['Online', social, media]), verbo([provides]), complemento([a, platform, for, women, to, share, their, experiences, and, reactions, in, undergoing, 'mammography,', including, 'humor,', positive, 'reflections,', and, encouragement, of, others, to, undergo, the, examination])]). relacion([sujeto(['Recently', we]), verbo([have]), complemento([shown, that, capsaicin, attenuates, the, strength, of, 'LTP', in, the, lateral, amygdala, '(', 'LA)', and, demonstrated, that, this, effect, is, mediated, by, the, transient, receptor, potential, '(', 'TRP)', channel, 'TRPV1'])]). relacion([sujeto(['Here', we, further, show, that, 'capsaicin,', which, is, thought, to]), verbo([act]), complemento([primarily, through, 'TRPV1,', modifies, long, term, depression, '(', 'LTD)', in, the, 'LA'])]). relacion([sujeto(['Whereas', 'LA-LTD', in, general, depends, on, the, acitvation, of, 'NMDA', 'receptors-', and, group, 'II', metabotropic, glutamate, receptors, '(', 'mGluR),', the, modifying, effect, of, capsaicin, on, 'LA-LTD', via, 'TRPM1', appears, to, be, specifically]), verbo([mediated]), complemento([by, group, 'I', mGluRs, and, in, interaction, with, another, member, of, the, 'TRP', 'family,', 'TRPC5'])]). relacion([sujeto(['Additionally,', intact, 'GABAergic', transmission, is]), verbo([required]), complemento([for, the, 'capsaicin-effect', to, take, place])]). relacion([sujeto(['This', is, the, first, documentation, that, beside, their, function, in, the, retina, 'TRPM1', proteins, are]), verbo([expressed]), complemento([in, the, brain, and, have, a, functional, relevance, in, modifying, synaptic, plasticity])]). relacion([sujeto(['Elevated', potassium]), verbo([maintains]), complemento([hair, cells, near, a, potential, where, transduction, currents, are, sufficient, to, depolarize, them, to, voltages, necessary, for, calcium, influx, and, synaptic, vesicle, fusion])]). relacion([sujeto(['With']), verbo([increased]), complemento(['stimulation,', hair, cell, depolarization, increases, the, frequency, of, quanta, 'released,', elevates, '[', 'K(+)', ']', cleft, and, depolarizes, the, afferent, to, potentials, at, which, smaller, and, smaller, 'EPSPs', would, be, sufficient, to, trigger, 'APs'])]). relacion([sujeto(['Fast', neurotransmitters]), verbo([act]), complemento([in, conjunction, with, slower, modulatory, effectors, that, accumulate, in, restricted, synaptic, spaces, found, at, giant, synapses, such, as, the, calyceal, endings, in, the, auditory, and, vestibular, systems])]). relacion([sujeto(['Here,', we, used, dual, 'patch-clamp', recordings, from, turtle, vestibular, hair, cells, and, their, afferent, neurons, to, show, that, potassium, ions, accumulating, in, the, synaptic, cleft]), verbo([modulated]), complemento([membrane, potentials, and, extended, the, range, of, information, transfer])]). relacion([sujeto(['Increased', potassium, concentration, in, the, cleft]), verbo([maintained]), complemento([the, hair, cell, near, potentials, that, promoted, the, influx, of, calcium, necessary, for, synaptic, vesicle, fusion])]). relacion([sujeto(['Depolarization', of, the, postsynaptic, afferent, could, also, elevate, potassium, in, the, synaptic, 'cleft,', and, would, depolarize, other, hair, cells, enveloped, by, the, same, neuritic, process]), verbo([increasing]), complemento([the, fidelity, of, neurotransmission, at, those, synapses, as, well])]). relacion([sujeto(['Collectively,', these, data, demonstrate, that, neuronal, activity, gives, rise, to, potassium, 'accumulation,', and]), verbo([suggest]), complemento([that, potassium, ion, action, on, 'HCN', channels, can, modulate, 'neurotransmission,', preserving, the, fidelity, of, 'high-speed', synaptic, transmission, by, dynamically, shifting, the, resting, potentials, of, both, presynaptic, and, postsynaptic, cells])]). relacion([sujeto([elegans, during, the, feeding, process, and, were]), verbo([recognized]), complemento([and, taken, up, by, the, active, transport, system, of, the, intestinal, cells])]). relacion([sujeto(['Moreover,', with, numerous, modifiable, carboxyl, groups, on, its, 'surface,', the, 'NPs', could]), verbo([act]), complemento([as, a, platform, to, build, multifunctional, probes, for, potential, applications, in, biosensing, and, assay, labeling])]). relacion([sujeto(['AtMYB44', is, a, multifaceted, transcriptional, factor, that, functions, in, many, physiological, processes, in, plants, but, whether, 'AtMYB44']), verbo([modulates]), complemento([the, plant, response, to, 'AHL', with, aspects, of, primary, root, elongation, remains, unknown])]). relacion([sujeto(['In', 'contrast,', an]), verbo([enhanced]), complemento(['promoting-impact', of, 3, 'OC6-HSL', on, primary, root, growth, was, observed, in, 'AtMYB44-overexpressing', plant, 'MYB44OTA'])]). relacion([sujeto(['Cellular', analysis, indicated, that, the, prolonged, primary, root, elicited, by, 3, 'OC6-HSL', is, the, consequence, of]), verbo([increased]), complemento([cell, division, in, the, meristem, zone, and, enhanced, cell, elongation, in, the, elongation, 'zone,', and, 'AtMYB44', may, act, as, a, positive, regulator, in, this, process])]). relacion([sujeto(['Furthermore,', we, demonstrated, that, 'AtMYB44', might]), verbo([participate]), complemento([in, the, 3, 'OC6-HSL-mediated', primary, root, growth, via, regulating, the, expression, of, 'cytokinin-', and, 'auxin-related', genes])]). relacion([sujeto(['To', this, 'end,', the, distributions, of, energy, levels, for, the, 'PE555', complex, were]), verbo([found]), complemento([to, be, similar, to, those, of, the, 'PE545', complex, despite, the, clear, differences, in, the, respective, protein, structures])]). relacion([sujeto(['In', the, 'PE555', complex, the, two, αβ, monomers, are, rotated, by, '∼73°', compared, to, the, 'PE545', structure]), verbo([leading]), complemento([to, a, water, filled, channel])]). relacion([sujeto(['Moreover,', the, connections, between, the, 'bilins,', which]), verbo([act]), complemento([as, pigments, in, these, 'aggregates,', and, the, protein, show, clear, differences, in, the, two, structures])]). relacion([sujeto(['In', 'addition,', the, partial, transition, charges, of, the]), verbo([involved]), complemento([bilins, have, been, determined, in, order, to, calculate, the, electronic, couplings, using, the, transition, charges, from, electrostatic, potentials, '(', 'TrEsp)', method])]). relacion([sujeto(['For', comparison, 'purposes,', the, couplings]), verbo([have]), complemento([been, extracted, using, the, 'point-dipole', approximation, as, well])]). relacion([sujeto(['On', average, the, coupling, values, predicted, by, the, dipole, approximation, are, slightly, larger, than, those, from, the, 'TrEsp', method]), verbo([leading]), complemento([to, enhanced, population, decay, rates, as, tested, in, 'ensemble-averaged', wave, packet, dynamics])]). relacion([sujeto(['Moreover,', the, exciton, dynamics, in, the, 'PE555', structure, is, significantly, slower, than, in, the, 'PE545', complex, due, to, the, smaller, coupling, values]), verbo([induced]), complemento([by, the, dissimilar, arrangements, of, the, monomers])]). relacion([sujeto(['The', effect, of, smoking, cessation, on, centrilobular, emphysema, '(', 'CLE)', and, centrilobular, nodularity, '(', 'CN),', two, manifestations, of, 'smoking-related', lung, injury, on, computed, tomography, '(', 'CT)', 'images,']), verbo([has]), complemento([not, been, clarified])]). relacion([sujeto(['Chest', 'CT', scans, from, 350, current, 'smokers,', 401, former, 'smokers,', and, 25, control, subjects, were, obtained, from, the, multicenter, 'COPDGene', 'Study,', a, 'Health', 'Insurance', 'Portability', and, 'Accountability', 'Act-compliant', study, approved, by, the, institutional, review, board, of, each]), verbo([participating]), complemento([clinical, study, center])]). relacion([sujeto(['Among', patients, with, longitudinal, 'CT', 'scans,', continued, smoking]), verbo([led]), complemento([to, a, slight, increase, in, 'CLE', '(', 'P', =, 0.13, ')', ',', whereas, sustained, abstinence, from, smoking, led, to, further, reduction, in, 'CN', '(', 'P', &, 'lt;0'])]). relacion([sujeto(['Differences', in, 'smoking-related', lung, disease, between, longitudinal, scans, of, current, smokers, and, longitudinal, scans, of, former, smokers]), verbo([suggest]), complemento([that, 'CN', may, be, reversible, on, smoking, cessation])]). relacion([sujeto(['Some', volatile, aromatic, solvents]), verbo([have]), complemento([similar, or, opposite, effects, to, anesthetics, in, the, central, nervous, system])]). relacion([sujeto(['Like', for, 'anesthetics,', the, mechanisms, of, action]), verbo([involved]), complemento([are, currently, the, subject, of, debate])]). relacion([sujeto(['This', paper, presents, an, in, vivo, study, to, determine, whether, direct]), verbo([binding]), complemento([or, effects, on, membrane, fluidity, best, explain, how, solvents, counterbalance, 'anesthesia\'s', depression, of, the, 'middle-ear', reflex, '(', 'MER)'])]). relacion([sujeto(['The', depth, of, anesthesia, was, standardized, based, on, the, magnitude, of, the, contraction, of, the, muscles]), verbo([involved]), complemento([in, the, 'MER,', determined, by, measuring, cubic, distortion, product, 'oto-acoustic', emissions, '(', 'DPOAEs)', while, triggering, the, bilateral, reflex, with, contralateral, acoustic, stimulation])]). relacion([sujeto(['Therefore,', aromatic, solvents, appear, to]), verbo([act]), complemento([directly, on, the, neuroreceptors, involved, in, the, acoustic, reflex, 'circuit,', rather, than, on, membrane, fluidity])]). relacion([sujeto(['Fuhrman']), verbo([nuclear]), complemento([grade, is, the, most, important, histological, parameter, to, predict, prognosis, in, a, patient, of, renal, cell, carcinoma, '(', 'RCC)'])]). relacion([sujeto(['However,', it, suffers, from, 'inter-observer', and, 'intra-observer', variation, giving, rise, to, need, of, a, parameter, that, not, only, correlates, with]), verbo([nuclear]), complemento([grade, but, is, also, objective, and, reproducible])]). relacion([sujeto(['Proliferation', is, the, measure, of, aggressiveness, of, a, tumour, and, it, is, strongly, correlated, with, 'Fuhrman']), verbo([nuclear]), complemento(['grade,', clinical, survival, and, recurrence, in, 'RCC'])]). relacion([sujeto(['This', study, was, designed, to, assess, the, prognostic, significance, of, 'MCM-2', by, comparing, it, with, 'Fuhrman']), verbo([nuclear]), complemento([grade, and, 'Ki-67'])]). relacion([sujeto([29, '%', ')', was]), verbo([found]), complemento([to, be, much, higher, than, 'Ki-67(median=13'])]). relacion([sujeto(['LI', of, 'MCM-2', was]), verbo([found]), complemento([to, correlate, significantly, with, 'LI', of, 'Ki-67(r=0'])]). relacion([sujeto(['Therefore,', they, can]), verbo([act]), complemento([as, surrogate, markers, for, grade, in, a, manner, that, is, more, objective, and, reproducible])]). relacion([sujeto(['Studies']), verbo([have]), complemento([shown, that, advanced, care, planning, improves, communication, and, reduces, suffering, for, patients, and, their, bereaved, caregivers])]). relacion([sujeto(['Despite', this, 'knowledge,', the, rates, of, advance, care, plans, are, low, and, 'physicians,', as, the, primary, 'gatekeepers,']), verbo([have]), complemento([made, little, progress, in, improving, their, rates])]). relacion([sujeto(['A', critical, discourse]), verbo([provides]), complemento([suggestions, to, eliminate, oppressive, ideologies, that, act, as, barriers, to, advanced, care, planning])]). relacion([sujeto(['Novel', 'silver(I)', complexes, of, coumarin, oxyacetate, ligands, and, their, phenanthroline, adducts]), verbo([have]), complemento([been, prepared, and, characterised, by, microanalytical, data, and, spectroscopic, techniques, '(', 'IR,', '(', 1, ')', 'H,', '(', 13, ')', 'C', 'NMR,', 'UV-Vis)'])]). relacion([sujeto(['The', experimental, spectroscopic, data]), verbo([have]), complemento([been, interpreted, on, the, basis, of, molecular, structure, modeling, and, subsequent, spectra, simulation, with, density, functional, theory, method])]). relacion([sujeto(['The']), verbo([binding]), complemento([modes, of, the, coumarins, and, phenanthroline, ligands, '(', 'monodentate,', 'bidentate,', 'bridging)', to, 'Ag(I)', have, been, theoretically, modelled, and, discussed, as, to, the, most, probable, ligand, binding, in, the, series, of, complexes, studied])]). relacion([sujeto(['The', antimicrobial, and, antifungal, activities]), verbo([have]), complemento([been, determined, and, the, complexes, were, found, to, have, mostly, moderate, antibacterial, activity, but, some, of, the, phenanthroline, adducts, were, found, to, have, antifungal, activity, against, the, clinically, important, fungus, 'C'])]). relacion([sujeto(['Preliminary', investigations, into, the, possible, mechanism, of, action, of, the, silver, complexes, indicated, that, they, did, not]), verbo([interact]), complemento([with, 'DNA', via, nuclease, activity, or, intercalation, but, the, ability, to, act, as, a, superoxide, dismutase, mimetic, may, be, related, to, their, antimicrobial, activity])]). relacion([sujeto(['Although', eosinophils, are, inflammatory, 'cells,', there, is]), verbo([increasing]), complemento([attention, on, their, immunomodulatory, roles])]). relacion([sujeto(['For', 'example,', murine, eosinophils, can, present, antigen, to, 'CD4(+)', 'T', helper, '(', 'Th)', 'cells,', but, it, remains, unclear, whether, human, eosinophils, also]), verbo([have]), complemento([this, ability])]). relacion([sujeto(['This', study, determined, whether, human, eosinophils, present, a, range, of, 'antigens,', including, 'allergens,', to]), verbo([activate]), complemento(['Th', 'cells,', and, characterized, their, expression, of, 'MHC', class, 'II', and, 'co-stimulatory', molecules, required, for, effective, presentation])]). relacion([sujeto(['Eosinophils', 'up-regulated', surface, expression, of, 'HLA-DR/DP/DQ,', 'CD80,', 'CD86', and, 'CD40', in, 'culture,']), verbo([increases]), complemento([that, were, sustained, over, 5, days, when, incubated, with, 'antigens,', including, 'HDM,', or, the, major, allergens, it, 'contains,', 'Der', p, 'I', or, 'Der', p, 'II'])]). relacion([sujeto(['Human', eosinophils, 'can,', 'therefore,']), verbo([act]), complemento([as, effective, 'antigen-presenting', cells, to, stimulate, varied, 'Th', cell, responses, against, a, panel, of, antigens, including, 'HDM,', 'TG', or, 'PPD,', an, ability, that, may, help, to, determine, the, development, of, allergic, disease])]). relacion([sujeto(['Reductive', cyclization, of, the, 2, ',', 4, ',', 5, -, trisubstituted, cyclohexenone, 16, using, dihydogen, in, the, presence, of, 'Raney', cobalt, afforded, compound, 17, '(', 60, '%', ')', that, could, be, elaborated, over, a, further, five, 'steps,', including, one]), verbo([involving]), complemento([a, cationic, cyclization, 'process,', into, the, racemic, modification, of, the, unusual, uleine, alkaloid, gilbertine])]). relacion([sujeto(['Naturally', occurring, anticancer, agents, and, their, derivatives]), verbo([act]), complemento([on, multiple, pathways, to, inhibit, carcinogenesis, and, their, inhibition, of, 'migration,', 'invasion,', 'growth,', 'survival,', and, metastasis, is, associated, with, downregulation, of, genes, associated, with, these, responses])]). relacion([sujeto(['Several', 'phytochemical-derived', anticancer, drugs, including, 'curcumin,', betulinic, 'acid,', phenethylisothiocyanate, and, 'celastrol,', and, many, others]), verbo([induce]), complemento([reactive, oxygen, 'species,', and, their, effects, on, gene, regulation, show, some, overlap, in, various, cancer, cell, lines])]). relacion([sujeto(['We', hypothesize, that, reactive, oxygen, 'species-inducing', anticancer, agents, and, many, other, natural, products]), verbo([target]), complemento([a, common, pathway, in, cancer, 'cells,', which, initially, involves, downregulation, of, specificity, protein, 1, '(', 'Sp1),', 'Sp3,', and, 'Sp4,', which, are, highly, expressed, in, 'tumors/cell', lines, derived, from, solid, tumors])]). relacion([sujeto(['This', hypothesis, is, supported, by, several, published]), verbo([reports]), complemento([showing, that, a, large, number, of, 'phytochemical-derived', anticancer, agents, downregulate, 'Sp1,', 'Sp3,', 'Sp4,', and, 'pro-oncogenic', 'Sp-regulated', genes, involved, in, cell, growth, '(', cyclin, 'D1', and, growth, factor, 'receptors),', survival, '(', 'bcl-2', and, 'survivin),', angiogenesis, and, migration, '(', 'MMP-9,', vascular, endothelial, growth, factor, and, its, 'receptors),', and, inflammation, '(', 'NF-kB)'])]). relacion([sujeto(['The', human, lens, contains, multiple, 'tryptophan-derived', compounds, that]), verbo([have]), complemento([significant, absorbance, bands, in, the, 'UVA', region, '(', λ, 315, -, 400, 'nm)', that, act, as, efficient, physical, filters, for, these, wavelengths])]). relacion([sujeto(['The', concentrations, of, many, of, these, 'UV', filter, compounds]), verbo([decrease]), complemento([with, increase, in, 'age,', resulting, in, diminished, 'protection,', increased, oxidative, damage, and, the, accumulation, of, modified, proteins, implicated, in, nuclear, cataract, formation])]). relacion([sujeto(['The', latter, may]), verbo([promote]), complemento([the, oxidation, of, 'free,', or, 'protein-bound,', 'o-aminophenols,', such, as, the, 'UV', filter, compounds, 3, -, hydroxykynurenine, '(', 3, 'OHKyn)', and, 3, -, hydroxyanthranilic, acid, '(', 3, 'OHAA)'])]). relacion([sujeto(['It', is, shown, here, that, 'Cu(II),', and, to, a, lesser, extent, 'Fe(III),']), verbo([enhance]), complemento([oxidation, of, free, 3, 'OHKyn,', 3, 'OHAA', and, 3, 'OHKyn', bound, to, specific, amino, acids, and, lens, 'proteins,', with, this, resulting, in, increased, 'cross-linking', of, lens, proteins])]). relacion([sujeto(['These', data, indicate, that, elevated, levels, of, transition, metal, ions, in, aging, lenses, can]), verbo([enhance]), complemento([the, loss, of, protective, 'UV', filter, 'compounds,', and, contribute, to, the, formation, of, 'high-molecular-mass', dysfunctional, crystallin, proteins, in, a, 'light-independent', manner])]). relacion([sujeto(['In', the, genus, 'Streptomyces,', carbon, utilization, is, of, significant, importance, for, the, expression, of, genes]), verbo([involved]), complemento([in, morphological, differentiation, and, antibiotic, production])]). relacion([sujeto(['However,', there, is, little, information, about, the, mechanism]), verbo([involved]), complemento([in, these, effects])]). relacion([sujeto(['In', the, present, 'work,', it, was]), verbo([found]), complemento([that, glucose, exerted, a, suppressive, effect, on, the, 'Streptomyces', coelicolor, actinorhodin, '(', 'Act)', and, undecylprodigiosin, '(', 'Red)', 'production,', as, well, as, in, its, morphological, differentiation])]). relacion([sujeto([coelicolor, grown, under, glucose, 'repression,', at, early, growth, 'stages,', a, negative, effect, was, exerted, on, the, transcription, of, genes]), verbo([involved]), complemento([in, 'Act', and, 'Red', 'production,', when, compared, with, 'non-repressive', conditions])]). relacion([sujeto(['Finally,', a, series, of, transcriptional, regulators]), verbo([involved]), complemento([in, both, processes, were, 'up-', or, 'down-regulated', by, glucose])]). relacion([sujeto(['Both', 'TA', and, 'OA']), verbo([act]), complemento([as, 'neurotransmitters,', neurohormones, and, neuromodulators, in, the, arthropod, nervous, system])]). relacion([sujeto(['Herein,', the, inhibitory, activity, of, 1, -, 'arylimidazole-2(3H)-thiones', '(', 'AITs)', was, tested, on, cloned, 'Drosophila', 'tyramine-β-hydroxylase', '(', 'DmTβH)']), verbo([expressed]), complemento([in, 'Bombyx', mori, strain])]). relacion([sujeto(['Radiolabelled', '(', 3, ')', 'H-TA', was, used, to, analyze, the, activity, of, 'AITs', exhibited, inhibitory, effects, on, 'DmTβH,', whose, 'ID50', values, range, from, 0.02, to, 2511, nM, where, 'DmTβH', was]), verbo([inhibited]), complemento([in, a, 'dose-dependent', manner, at, pH, 7.6, and, 25, °, 'C', during, a, 30, min, of, incubation])]). relacion([sujeto(['One', noteworthy, category, includes, individuals, who]), verbo([have]), complemento([made, serious, suicide, 'attempts,', epidemiologically, very, similar, to, those, completing, suicide])]). relacion([sujeto(['This', behavioral, category, is, 'important,', since, interviewing, survivors, of, a, potentially, lethal, incident, of, 'self-harm', enables, a, detailed, investigation, of, the, psychological, process]), verbo([leading]), complemento([to, the, suicidal, act])]). relacion([sujeto(['We']), verbo([found]), complemento([a, large, variety, of, operational, 'definitions,', reflecting, the, lack, of, consensus, regarding, terminology, and, criteria, related, to, the, term])]). relacion([sujeto(['We', undertook, the, challenge, of, developing, an, integrative, and, comprehensive, set, of, criteria, of, serious, suicide, attempt, and]), verbo([suggest]), complemento([a, definition, comprising, three, key, 'dimensions:', medical, 'lethality,', potential, lethality, of, the, method, 'used,', and, severity, of, the, objective, circumstances, of, the, suicide, intent])]). relacion([sujeto(['Preoperative', chemoradiotherapy, and, standardized, radical, surgery, with, total, mesorectal, excision]), verbo([have]), complemento([been, established, as, the, '\'', gold, 'standard\'', for, treating, these, patients])]). relacion([sujeto(['Two', of, them, '(', 'ADORE,', 'CAO/ARO/AIO-04)', appeared, to]), verbo([find]), complemento([a, 'disease-free', survival, benefit, for, patients, treated, with, the, combination, therapy])]). relacion([sujeto(['Endangered', 'Species', 'Act', '(', 'ESA)']), verbo([requires]), complemento([that, the, &, 'quot;best', available, scientific, and, commercial, 'data"', be, used, to, protect, imperiled, species, from, extinction, and, preserve, biodiversity])]). relacion([sujeto(['However,', it, does, not]), verbo([provide]), complemento([specific, guidance, on, how, to, apply, this, mandate])]). relacion([sujeto(['Many', interviewees]), verbo([expressed]), complemento([a, desire, to, continue, the, current, 'case-by-case', approach, for, handling, hybridization, 'issues,', but, some, wanted, more, guidance, on, procedures, '(', i])]). relacion([sujeto(['Field-level', information, can]), verbo([provide]), complemento([critical, insight, into, which, policies, are, working, '(', or, not, 'working)', and, why])]). relacion([sujeto(['Programs', that, were, participatory, and, used, digital, devices, were, more, likely, to]), verbo([report]), complemento([management, 'actions,', which, was, consistent, with, cases, in, 'Ethiopia,', 'Greenland,', and, 'Australia'])]). relacion([sujeto(['Programs', engaging, volunteers, were, more, frequently]), verbo([reported]), complemento([as, 'ongoing,', but, those, involving, digital, data, entry, were, less, often, sustained, when, data, collectors, were, volunteers])]). relacion([sujeto(['Endangered', 'Species', 'Act']), verbo([has]), complemento([been, hampered, by, a, lack, of, consistency, and, 'transparency,', which, can, be, improved, by, implementing, a, standardized, approach, for, evaluating, species, status, and, developing, measurable, recovery, criteria])]). relacion([sujeto(['Protecting', all, area, within, the, designated, critical, habitat]), verbo([maintained]), complemento([a, similar, level, '(', 83.9, -, 99.9, '%', ')', of, species, persistence, as, the, 'baseline,', whereas, maximum, mining, greatly, reduced, persistence, '(', 0.51, -, 38.4, '%', 'maintained)'])]). relacion([sujeto(['The', 3, persistence, measures]), verbo([provided]), complemento([complementary, insights, reflecting, different, aspects, of, habitat, availability, '(', total, 'area,', number, of, 'patches,', patch, 'size,', and, 'connectivity)'])]). relacion([sujeto(['By', focusing, on, amount, and, distribution, of, 'habitat,', our, method]), verbo([provides]), complemento([a, means, of, assessing, the, status, of, 'data-poor', species, to, inform, decision, making, under, the, 'Endangered', 'Species', 'Act'])]). relacion([sujeto(['Diagnosis', of, developmental, or, congenital, prosopagnosia, '(', 'CP)']), verbo([involves]), complemento(['self-report', of, everyday, face, recognition, 'difficulties,', which, are, corroborated, with, poor, performance, on, behavioural, tests])]). relacion([sujeto(['This', approach]), verbo([requires]), complemento([accurate, 'self-evaluation'])]). relacion([sujeto(['We', examine, the, extent, to, which, typical, adults]), verbo([have]), complemento([insight, into, their, face, recognition, abilities, across, four, experiments, involving, nearly, 300, participants])]). relacion([sujeto(['The', experiments, used, five, tests, of, face, recognition, 'ability:', two, that, tap, into, the, ability, to, learn, and]), verbo([recognize]), complemento([previously, unfamiliar, faces, '[', the, 'Cambridge', 'Face', 'Memory', 'Test,', 'CFMT;', 'Duchaine,', 'B'])]). relacion([sujeto([1, ;, and, a, newly, devised, test, based, on, the, 'CFMT', but, where, the, study, phases]), verbo([involve]), complemento([watching, short, movies, rather, than, viewing, static, 'faces-the', 'CFMT-Films]', and, three, that, tap, face, matching, '[', 'Benton', 'Facial', 'Recognition', 'Test,', 'BFRT;', 'Benton,', 'A'])]). relacion([sujeto(['Overall,', we]), verbo([find]), complemento([that, adults, with, typical, face, recognition, abilities, have, only, modest, insight, into, their, ability, to, recognize, faces, on, behavioural, tests])]). relacion([sujeto(['In', a, fifth, 'experiment,', we, assess, 'self-reported', face, recognition, ability, in, people, with, 'CP', and]), verbo([find]), complemento([that, some, people, who, expect, to, perform, poorly, on, behavioural, tests, of, face, recognition, do, indeed, perform, poorly])]). relacion([sujeto(['However,', it, is, not, yet, clear, whether, individuals, within, this, group, of, poor, performers]), verbo([have]), complemento([greater, levels, of, insight, '(', i])]). relacion([sujeto(['Although', the, exact]), verbo([cause]), complemento([of, 'IBS', remains, 'uncertain,', some, studies, have, shown, that, the, inflammation, and, cytokine, imbalance, may, act, as, potential, etiological, factors])]). relacion([sujeto(['Higher', serum, level, of, 'IL-6,', 'IL-8', and, 'TNF-α', in, 'IBS']), verbo([suggests]), complemento([an, important, role, of, cytokines, as, immune, mediators, in, the, pathogenesis, of, this, functional, 'GI', disorder])]). relacion([sujeto(['Specific', members, of, the, transient, receptor, potential, '(', 'TRP)', superfamily, of, cation, channels]), verbo([act]), complemento([as, important, 'Ca(2+)', influx, pathways, in, endothelial, 'cells,', and, are, involved, in, 'endothelium-dependent', 'vasodilation,', regulation, of, barrier, 'permeability,', and, angiogenesis])]). relacion([sujeto(['ROS', and, 'RNS', can]), verbo([modulate]), complemento([the, activity, of, certain, 'TRP', channels, mainly, by, modifying, specific, cysteine, residues, or, by, stimulating, the, production, of, second, messengers])]). relacion([sujeto(['The', structures, of, these, coordination, polymers]), verbo([have]), complemento([been, determined, by, 'X-ray', diffraction, at, both, 'room-', and, low, temperature, '(', 110, 'K),', showing, a, general, shortening, in, 'Cu-S,', 'Cu-X', and, 'Cu-Cu', bond, lengths, at, low, temperatures])]). relacion([sujeto([1, and, 2, are, 'isostructural,', consisting, of, layers, in, which, the, halogen, ligands]), verbo([act]), complemento([as, μ3, -, bridges, joining, two, 'Cu1', and, one, 'Cu2', atoms, whereas, in, 3, the, iodine, ligands, is, as, μ4, -, mode, but, the, layers, are, 'quasi-isostructural', with, 1, or, 2])]). relacion([sujeto(['DFT', calculations]), verbo([have]), complemento([been, used, to, rationalize, these, observations])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([a, high, potential, for, this, novel, and, promising, 'stimuli-responsive', materials])]). relacion([sujeto(['Rejected', individuals, may, then, harness, 'revenge\'s']), verbo([associated]), complemento([positive, affect, to, repair, their, mood])]). relacion([sujeto(['These', effects, were]), verbo([mediated]), complemento([by, sadistic, impulses, toward, finding, aggression, pleasant, '(', 'Studies', 2, and, 4, ')'])]). relacion([sujeto(['Suggesting', the, occurrence, of, actual, mood, 'repair,', rejected, 'participants\'', affective, states, were, equivalent, to, their, accepted, counterparts, after, an]), verbo([act]), complemento([of, aggression, '(', 'Studies', 5, and, 6, ')'])]). relacion([sujeto(['This', mood, repair, occurred, through, a, dynamic, interplay, between, preaggression, affect, and, aggression, 'itself,', and, was, driven, by]), verbo([increases]), complemento([in, positive, affect, '(', 'Studies', 5, and, 6, ')'])]). relacion([sujeto(['Together,', these, findings]), verbo([suggest]), complemento([that, the, 'rejection-aggression', link, is, 'driven,', in, 'part,', by, the, desire, to, return, to, affective, homeostasis])]). relacion([sujeto(['We', focus, specifically, on, the]), verbo([act]), complemento([of, crying, 'and,', based, on, role, congruity, 'theory,', argue, that, a, male, employee, crying, in, response, to, negative, performance, feedback, will, be, seen, as, atypical, behavior, by, the, feedback, 'provider,', which, will, bias, evaluations, of, the, employee, on, a, number, of, different, outcome, 'variables,', including, performance, 'evaluations,', assessments, of, leadership, 'capability,', and, written, recommendations])]). relacion([sujeto(['That', 'is,', we, expect, an, interactive, effect, between, gender, and, crying, on, our, 'outcomes,', an, effect, that, will, be]), verbo([mediated]), complemento([by, perceived, typicality])]). relacion([sujeto(['We']), verbo([find]), complemento([support, for, our, moderated, mediation, model, in, a, sample, of, 169, 'adults,', indicating, that, men, who, cry, in, response, to, negative, performance, feedback, will, experience, biased, evaluations, from, the, feedback, provider])]). relacion([sujeto(['Thermal', decarboxylation, of, '[', 'Ru(pbn)2(CO)(COOH)](+)', 'and/or', '[', 'Ru(pbn)2(CO)(COO)](0)']), verbo([induces]), complemento([a, 'two-electron', reduction, of, pbn, to, form, '[', 'Ru(pbn)(pbnHH)(CO)(OH2)](2+)', '[', pbnHH, =, 2, -, '(', 'pyridin-2-yl)-5,10-dihydrobenzo[b]-1,5-naphthyridine]', in, 'H2O'])]). relacion([sujeto(['Functionally,', 'TRAFs']), verbo([act]), complemento([both, as, a, scaffold, 'and/or', enzymatic, proteins, to, regulate, activation, of, 'mitogen-activated', protein, kinases, '(', 'MAPKs)', and, transcription, factors, of, nuclear, 'factor-κB', family, '(', 'NF-κB)'])]). relacion([sujeto(['Given', the, wide, variety, of, stimuli, intracellularly, conveyed, by, 'TRAF', 'proteins,', they, are, physiologically]), verbo([involved]), complemento([in, multiple, biological, 'processes,', including, embryonic, 'development,', tissue, homeostasis, and, regulation, of, innate, and, adaptive, immune, responses])]). relacion([sujeto(['In', the, last, few, 'years,', it]), verbo([has]), complemento([become, increasingly, evident, the, involvement, of, 'TRAF7,', the, last, member, of, the, 'TRAF', family, to, be, 'discovered,', in, the, genesis, and, progression, of, several, human, 'cancers,', placing, 'TRAF7', in, the, spotlight, as, a, novel, tumor, suppressor, protein])]). relacion([sujeto(['A', sharp, resonant, mode, and, a, 'zero-scattering', dip, are]), verbo([found]), complemento([to, be, introduced, in, the, forward, scattering, spectrum, of, a, 'Si', 'NS', by, putting, it, on, a, 50, -, 'nm-thick', gold, film])]). relacion([sujeto(['It', is, revealed, that, the, sharp, resonant, mode, arises, from, a, new, magnetic, dipole]), verbo([induced]), complemento([by, the, electric, dipole, and, its, mirror, image, while, the, 'zero-scattering', dip, originates, from, the, destructive, interference, between, the, new, magnetic, dipole, and, the, original, one, together, with, its, mirror, image])]). relacion([sujeto(['More', 'interestingly,', the, use, of, a, thin, silver, film, can]), verbo([lead]), complemento([to, vivid, scattering, light, with, different, color, indices])]). relacion([sujeto(['Our', findings, indicate, that, 'dielectric-metal', hybrid, systems, composed, of, semiconductor, 'NSs', and, thin, metal, films]), verbo([act]), complemento([as, attractive, platforms, on, which, novel, nanoscale, plasmonic, devices, can, be, realized])]). relacion([sujeto(['Solar', 'H2', generation, from, water]), verbo([has]), complemento([been, intensively, investigated, as, a, clean, method, to, convert, solar, energy, into, hydrogen, fuel])]). relacion([sujeto(['During', the, past, few, 'decades,', many, studies]), verbo([have]), complemento([demonstrated, that, metal, complexes, can, act, as, efficient, photoactive, materials, for, photocatalytic, 'H2', production])]). relacion([sujeto(['Here', we, demonstrate, a, method, by, which, reciprocity, can]), verbo([maintain]), complemento([cooperation, in, a, 'large-scale', public, goods, game, '(', 'PGG)'])]). relacion([sujeto(['In', 'response,', low, 'PGG', contributors]), verbo([increase]), complemento([their, contributions, if, both, neighbours, defect, in, the, 'PD'])]). relacion([sujeto(['Our', findings]), verbo([suggest]), complemento([that, this, simple, &, 'quot;local-to-global"', intervention, facilitates, 'large-scale', cooperation])]). relacion([sujeto(['α-Synuclein', is, an, intrinsically, disordered, protein, that, is]), verbo([associated]), complemento([with, the, pathogenesis, of, 'Parkinson\'s', disease, through, the, processes, involved, in, the, formation, of, amyloid, fibrils])]). relacion([sujeto([α, and, 'β-synuclein', are, homologous, proteins]), verbo([found]), complemento([at, comparable, levels, in, presynaptic, terminals, but, 'β-synuclein', has, a, greatly, reduced, propensity, to, aggregate, and, indeed, has, been, found, to, inhibit, 'α-synuclein', aggregation])]). relacion([sujeto(['In', 'particular,', we, show, that, 'β-synuclein', strongly]), verbo([suppresses]), complemento([both, 'lipid-induced', aggregation, and, secondary, nucleation, of, 'α-synuclein', by, competing, for, binding, sites, at, the, surfaces, of, lipid, vesicles, and, 'fibrils,', respectively])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, 'β-synuclein', can, act, as, a, natural, inhibitor, of, 'α-synuclein', aggregation, by, reducing, both, the, initiation, of, its, 'self-assembly', and, the, proliferation, of, its, aggregates])]). relacion([sujeto(['A', 'long-standing', paradigm, in, drug, discovery]), verbo([has]), complemento([been, the, concept, of, designing, maximally, selective, drugs, to, act, on, individual, targets, considered, to, underlie, a, disease, of, interest])]). relacion([sujeto(['Nonetheless,', although, some, drugs]), verbo([have]), complemento([proven, to, be, 'successful,', many, more, potential, drugs, identified, by, the, &, 'quot;one', 'gene,', one, 'drug,', one, 'disease"', approach, have, been, found, to, be, less, effective, than, expected, or, to, cause, notable, side, effects])]). relacion([sujeto(['The', complexity, of, the, molecular, and, cellular, bases, of, systems, responses, to, drug, interventions]), verbo([has]), complemento([fostered, an, increased, interest, in, 'systems-oriented', approaches, to, drug, discovery])]). relacion([sujeto(['Consonant', with, this, knowledge, of, the, multifactorial, mechanistic, basis, of, drug, sensitivity, and, resistance, is, the, application, of, 'network-based', approaches, for, the, identification, of, molecular, '(', 'multi-)feature', signatures]), verbo([associated]), complemento([with, desired, '(', 'multi-)drug', phenotypic, profiles])]). relacion([sujeto(['This', chapter, illustrates, the, principal, network, analysis, and, inference, techniques, which]), verbo([have]), complemento([found, application, in, 'systems-oriented', drug, design, and, considers, their, benefits, and, drawbacks, in, relation, to, the, nature, of, the, data, produced, by, network, pharmacology])]). relacion([sujeto(['Growing', evidences]), verbo([suggest]), complemento([that, cardiac, matrix, stiffness, and, differential, expressions, of, miRNAs, play, a, crucial, role, in, stem, cell, survival, and, differentiation])]). relacion([sujeto(['Transplanted', stem, cells, may]), verbo([act]), complemento([in, an, autocrine, 'and/or', paracrine, manner, to, regenerate, the, dead, myocardium])]). relacion([sujeto(['These', exosomes, carry, microRNAs, '(', 'miRNAs)', that, may]), verbo([regulate]), complemento([stem, cell, differentiation, into, a, specific, lineage])]). relacion([sujeto(['MicroRNAs', may, also, contribute, to, stiffness, of, surrounding, matrix, by]), verbo([regulating]), complemento([extracellular, matrix, '(', 'ECM)', turnover])]). relacion([sujeto(['The', survival, of, transplanted, stem, cell, depends, on, its, autophagic, process, that]), verbo([maintains]), complemento([cellular, homeostasis])]). relacion([sujeto(['Therefore,', 'exosomes,', 'miRNAs,', extracellular, matrix, 'turnover,', and, autophagy, may]), verbo([have]), complemento([an, integral, role, in, improving, the, efficacy, of, 'SCT'])]). relacion([sujeto(['Partial', nitritation, 'is,', 'however,', a, critical, bottleneck, for, the, nitrogen, removal, since, it, is, often, difficult, to]), verbo([maintain]), complemento([the, right, proportions, of, 'NO2-N', and, 'NH4-N', during, long, periods, of, time, for, 'Anammox', process])]). relacion([sujeto(['Here,', zeolite]), verbo([acted]), complemento([as, a, preserving, reservoir, of, ammonium, where, both, sorption, and, desorption, took, place, when, needed, and, this, caused, the, 'Anammox-zeolite', system, to, act, as, a, buffer, system, to, generate, a, stable, effluent])]). relacion([sujeto(['Therefore,', the, 'FARSEEING', '(', 'FAll', 'Repository', for, the, design, of, 'Smart', and, 'sElf-adaptive', 'Environments', prolonging, 'Independent', 'livinG)', consortium, and]), verbo([associated]), complemento([partners, started, to, build, up, a, 'meta-database', of, 'real-world', falls])]). relacion([sujeto(['Between', 'January', 2012, and, 'December', 2015, more, than, 300, 'real-world', fall, events]), verbo([have]), complemento([been, recorded])]). relacion([sujeto(['A', signal, processing, and, fall, verification, procedure]), verbo([has]), complemento([been, developed, and, applied, to, the, data])]). relacion([sujeto(['The', fall, events]), verbo([have]), complemento([been, recorded, within, several, 'studies,', with, different, 'methods,', and, in, different, populations])]). relacion([sujeto(['Recent', data]), verbo([suggest]), complemento([that, lateral, signalling, can, be, mediated, both, by, junctional, contacts, between, neighbouring, cells, and, via, cellular, protrusions, that, allow, 'non-neighbouring', cells, to, interact, with, one, another, at, a, distance])]). relacion([sujeto(['However,', it, remains, unclear, precisely, how, signalling]), verbo([mediated]), complemento([by, these, distinct, types, of, 'cell-cell', contact, can, physically, contribute, to, the, generation, of, complex, patterns, without, the, assistance, of, diffusible, morphogens, or, 'pre-patterns'])]). relacion([sujeto(['We', show, that, allowing, the, signalling, kinetics, to, differ, at, junctional, versus, 'protrusion-mediated', 'contacts,', an, assumption, inspired, by, recent, data, which, show, that, the, cleavage, of, 'Notch', in, several, systems]), verbo([requires]), complemento([both, 'Delta', binding, and, the, application, of, mechanical, 'force,', permits, individual, cells, to, act, to, promote, both, lateral, activation, and, lateral, inhibition])]). relacion([sujeto(['The', hormone, fluctuations, that, an, animal, experiences, during, ovulation, can]), verbo([have]), complemento([lifelong, effects, on, developing, offspring])]). relacion([sujeto(['These', hormones, may]), verbo([act]), complemento([as, an, adaptive, 'mechanism,', allowing, offspring, to, be, '\'', 'pre-programmed\'', to, survive, in, an, unstable, environment])]). relacion([sujeto(['We', show, that, female, zebra, finches, '(', 'Taeniopygia', 'guttata)', exposed, to, embryonic, 'CORT', produce, daughters, that]), verbo([have]), complemento([equal, reproductive, success, '(', clutch, 'sizes,', 'fertility,', hatching, 'success)', compared, with, the, daughters, produced, from, untreated, 'mothers,', but, their, offspring, had, accelerated, 'post-hatching', growth, rates, and, were, significantly, heavier, by, nutritional, independence])]). relacion([sujeto(['Post-translational', modifications, '(', 'PTM)', affecting, 'E2', function, and, stability]), verbo([have]), complemento([been, demonstrated, for, multiple, types, of, papillomaviruses])]). relacion([sujeto(['Here', we, describe, the, first, phosphorylation, event, of, a]), verbo([conserved]), complemento([tyrosine, '(', 'Y)', in, the, bovine, papillomavirus, type, 1, '(', 'BPV-1)', 'E2', protein, at, amino, acid, 102])]). relacion([sujeto(['While', its, 'phospho-deficient', mutant, phenylalanine, '(', 'F)']), verbo([activated]), complemento([both, transcription, and, replication, in, luciferase, reporter, 'assays,', the, mutant, that, may, act, as, a, 'phospho-mimetic,', 'Y102', to, glutamate, '(', 'E),', lost, both, activities])]). relacion([sujeto(['The', 'E2', 'Y102F', protein]), verbo([interacted]), complemento([with, cellular, 'E2-binding', factors, and, the, viral, helicase, 'E1,', however, in, 'contrast,', 'Y102E', associated, with, only, a, subset, and, was, unable, to, bind, to, 'E1'])]). relacion([sujeto(['While', 'Y102F', fully, supported, transient, viral, 'DNA', 'replication,', 'BPV', genomes, encoding, this, mutation, as, well, as, 'Y102E', were, not]), verbo([maintained]), complemento([as, stable, episomes, in, murine, 'C127', cells])]). relacion([sujeto(['We', hypothesize, that, the, resulting, inhibition, of, viral, transcription, and, replication, in, basal, epithelial, cells]), verbo([prevents]), complemento([the, development, of, a, lytic, infection])]). relacion([sujeto(['One', approach, to, better, understanding, the, viral, replicative, cycle, -, and, potential, therapies, to]), verbo([target]), complemento([it, -, is, examining, 'post-translational', modification, of, viral, proteins, and, its, effect, on, function])]). relacion([sujeto(['Here', we]), verbo([have]), complemento([discovered, that, the, viral, transcription, and, replication, regulator, bovine, papillomavirus, type, 1, '(', 'BPV-1)', 'E2', is, phosphorylated, at, tyrosine, residue, 'Y102'])]). relacion([sujeto(['This', study, highlights, the, influence, of, 'post-translational', modifications, on, viral, protein, function, and]), verbo([provides]), complemento([additional, insight, into, the, complex, interplay, between, papillomaviruses, and, their, hosts])]). relacion([sujeto(['Once', 'activated,', 'RIG-I']), verbo([interacts]), complemento([with, polyubiquitin, chains, generated, by, 'TRIM25', and, binds, 'MAVS,', leading, to, the, production, of, type, 'I', 'IFN'])]). relacion([sujeto(['Upon', 'activation,', we, show, that, 'TRIM25', is, redistributed, into, cytoplasmic, dots]), verbo([associated]), complemento([with, stress, 'granules,', while, 'RIG-I', associates, with, 'TRM25/stress', granules, and, with, mitochondrial, 'MAVS'])]). relacion([sujeto(['In', 'addition,', 'MAVS', competes, with, 'TRIM25', for, 'RIG-I', 'binding,', and, this]), verbo([suggests]), complemento([that, upon, 'TRIM25', mediated, activation, of, 'RIG-I,', 'RIG-I', moves, away, from, 'TRIM25', to, interact, with, 'MAVS', at, the, mitochondria])]). relacion([sujeto(['By', 'contrast,', the, influenza, 'A', virus, '(', 'IAV)', 'NS1', protein]), verbo([interacts]), complemento([with, 'RIG-I', and, 'TRIM25', in, specific, areas, in, the, cell, 'cytoplasm,', and, inhibits, the, formation, of, 'TRIM25', 'homocomplexes,', but, not, of, 'RIG-I/TRIM25', 'heterocomplexes,', preventing, the, formation, of, 'RIG-I/MAVS', complexes])]). relacion([sujeto(['Thus,', we]), verbo([have]), complemento([localized, spatially, in, the, cell, different, complexes, formed, between, 'RIG-I,', 'TRIM25', and, 'MAVS,', in, the, presence, and, absence, of, two, viral, 'IFN', antagonistic, proteins])]). relacion([sujeto(['Viruses', are]), verbo([recognized]), complemento([by, 'Pathogen', 'Recognition', 'Receptors', '(', 'PRR),', like, the, 'RIG-I', like, receptor, '(', 'RLR)', 'family,', that, activate, a, signaling, cascade, that, induces, 'IFN', production])]). relacion([sujeto(['In', the, present, study, we, 'visualized,', for, the, first, time, in, 'cells,', both, in, overexpression, and, endogenous, 'levels,', complexes, formed, among, key, proteins]), verbo([involved]), complemento([in, this, innate, immune, signaling, pathway])]). relacion([sujeto(['Through', different, techniques, we, were, able, to, analyze, how, these, proteins, are, distributed, and, reorganized, spatially, within, the, cell, in, order, to, transmit, the, signal]), verbo([leading]), complemento([to, an, efficient, antiviral, state])]). relacion([sujeto(['In', 'addition,', this, work, presents, a, new, means, by, 'how,', when, and, where, viral, proteins, can]), verbo([target]), complemento([these, pathways, and, act, against, the, host, immune, system, in, order, to, counteract, the, activation, of, the, immune, response])]). relacion([sujeto(['Neutrophils']), verbo([act]), complemento([as, a, first, line, of, defense, against, bacterial, and, fungal, 'infections,', but, they, are, also, important, effectors, of, acute, and, chronic, inflammation])]). relacion([sujeto(['Genome-wide', association, studies]), verbo([have]), complemento([established, that, the, gene, encoding, the, protein, tyrosine, phosphatase, nonreceptor, 22, '(', 'PTPN22)', makes, an, important, contribution, to, susceptibility, to, autoimmune, 'disease,', notably, rheumatoid, arthritis])]). relacion([sujeto(['Although', 'PTPN22', is, most, highly]), verbo([expressed]), complemento([in, 'neutrophils,', its, function, in, these, cells, remains, poorly, characterized])]). relacion([sujeto(['We', show, in, this, article, that, neutrophil, effector, 'functions,', including, 'adhesion,', production, of, reactive, oxygen, 'species,', and, degranulation]), verbo([induced]), complemento([by, immobilized, immune, 'complexes,', were, reduced, in, 'Ptpn22(-/-)', neutrophils])]). relacion([sujeto(['Ptpn22(-/-)', mice, were, protected, from, immune, 'complex-mediated', 'arthritis,']), verbo([induced]), complemento([by, the, transfer, of, arthritogenic, serum])]). relacion([sujeto(['Our', data]), verbo([suggest]), complemento([an, important, role, for, 'PTPN22-dependent', dephosphorylation, 'events,', which, are, required, to, enable, full, 'FcγR-induced', 'activation,', pointing, to, an, important, role, for, this, molecule, in, neutrophil, function])]). relacion([sujeto(['The', control, of, the, excitability, in, magnocellular, neurosecretory, cells, '(', 'MNCs)', of, the, supraoptic, nucleus]), verbo([has]), complemento([been, attributed, mainly, to, synaptic, inputs, from, circunventricular, organs])]). relacion([sujeto(['However,', nitric, oxide, '(', 'NO),', a, gaseous, messenger, produced, in, this, nucleus, during, isotonic, and, 'short-term', hypertonic, 'conditions,', is, an, example, of, a, modulator, that, can]), verbo([act]), complemento([directly, on, 'MNCs', to, modulate, their, firing, rate])]). relacion([sujeto(['NO']), verbo([inhibits]), complemento([the, electrical, excitability, of, 'MNCs,', leading, to, a, decrease, in, the, release, of, vasopressin, and, oxytocin])]). relacion([sujeto(['Because', 'NO']), verbo([acts]), complemento([independently, of, synaptic, 'inputs,', we, hypothesized, that, ion, channels, present, in, 'MNCs', are, the, targets, of, 'NO'])]). relacion([sujeto(['Our', results, show, that, blockade, of, 'HCN', channels, by, 'ZD7288']), verbo([decreases]), complemento(['MNC', firing, rate, with, significant, consequences, on, the, release, of, 'OT', and, 'VP,', measured, by, radioimmunoassay])]). relacion([sujeto(['NO']), verbo([induced]), complemento([a, significant, reduction, in, 'HCN', currents, by, binding, to, cysteine, residues, and, forming, 'S-nitrosothiol', complexes])]). relacion([sujeto(['Cells', in, our, organism, live, in, a, liquid, environment, whose, composition, and, osmolality, are]), verbo([maintained]), complemento([within, tight, limits])]). relacion([sujeto(['OT', and, 'VP']), verbo([act]), complemento([on, the, kidneys, controlling, the, excretion, of, water, and, sodium, to, maintain, homeostasis])]). relacion([sujeto(['NO', reacts, with, cysteine, residues, '(', 'S-nitrosylation)', on, 'hyperpolarization-activated', and, 'nucleotide-gated', cation, channels]), verbo([decreasing]), complemento([the, firing, rate, of, 'MNCs', and, the, consequent, secretion, of, 'VP', and, 'OT'])]). relacion([sujeto(['Community-associated', '(', 'CA)-CDI']), verbo([has]), complemento([increased, over, the, past, decades])]). relacion([sujeto(['It']), verbo([has]), complemento([been, postulated, that, asymptomatic, toxigenic, 'C'])]). relacion([sujeto([difficile, isolates, from, the, hospitals, had, a, matching, ribotype, isolated, from, the, 'community,']), verbo([suggesting]), complemento([that, transmission, between, these, two, settings, is, occurring])]). relacion([sujeto([difficile, strains]), verbo([causing]), complemento([symptomatic, infection, were, similar, to, those, causing, asymptomatic, infection, and, patients, exposed, to, antimicrobials, prior, to, admission, were, more, likely, to, develop, symptomatic, infection, '(', 'OR', 2.94, ;, 95, '%', 'CI', 1.2, -, 7.14, ')'])]). relacion([sujeto(['Our', findings]), verbo([suggest]), complemento([that, development, of, 'CDI', symptoms, in, a, setting, without, establishment, of, hospital, epidemics, with, binary, toxin, producing, 'C'])]). relacion([sujeto(['Here,', we]), verbo([report]), complemento([that, serotonin, '(', 5, -, 'HT)', and, 'arginine-vasopressin', '(', 'AVP)', act, in, opposite, ways, in, the, hypothalamus, to, regulate, dominance, and, aggression, in, females, and, males])]). relacion([sujeto(['Hypothalamic', injection, of, a, 5, -, 'HT1a', agonist]), verbo([stimulated]), complemento([aggression, in, female, hamsters, and, inhibited, aggression, in, 'males,', whereas, injection, of, 'AVP', inhibited, aggression, in, females, and, stimulated, aggression, in, males])]). relacion([sujeto(['Striking', sex, differences, were, also, identified, in, the, neural, mechanisms]), verbo([regulating]), complemento([dominance])]). relacion([sujeto(['Acquisition', of, dominance, was]), verbo([associated]), complemento([with, activation, of, 5, -, 'HT', neurons, within, the, dorsal, raphe, in, females, and, activation, of, hypothalamic, 'AVP', neurons, in, males])]). relacion([sujeto(['Further,', because, systemically, administered, fluoxetine]), verbo([increased]), complemento([aggression, in, females, and, substantially, reduced, aggression, in, 'males,', there, may, be, substantial, gender, differences, in, the, clinical, efficacy, of, commonly, prescribed, 5, -, 'HT-active', drugs, such, as, selective, 5, -, 'HT', reuptake, inhibitors])]). relacion([sujeto(['These', data]), verbo([suggest]), complemento([that, the, treatment, of, psychiatric, disorders, such, as, 'PTSD', may, be, more, effective, with, the, use, of, 5, -, 'HT-targeted', drugs, in, females, and, 'AVP-targeted', drugs, in, males])]). relacion([sujeto(['The', dermal, adipose, layer, expands, concomitantly, with, hair, follicle, 'downgrowth,']), verbo([providing]), complemento([a, paradigm, for, studying, coordinated, changes, of, surrounding, lineages, with, a, regenerating, tissue])]). relacion([sujeto(['Using', cell, 'type-specific', deletion, of, 'Smo,', a, gene]), verbo([required]), complemento([in, 'SHH-receiving', 'cells,', we, found, that, 'SHH', does, not, act, on, hair, 'follicles,', 'adipocytes,', endothelial, 'cells,', and, hematopoietic, cells, for, adipogenesis])]). relacion([sujeto(['Instead,', 'SHH']), verbo([acts]), complemento([directly, on, adipocyte, 'precursors,', promoting, their, proliferation, and, their, expression, of, a, key, adipogenic, 'gene,', peroxisome, 'proliferator-activated', receptor, γ, '(', 'Pparg),', to, induce, dermal, adipogenesis])]). relacion([sujeto(['However,', the, last, twenty, years]), verbo([has]), complemento([seen, innovations, and, advancements, in, health, information, technology, that, were, unimaginable, at, that, time])]). relacion([sujeto(['Sesquiterpene', lactones, '(', 'STLs)', are, a, large, and, structurally, diverse, group, of, plant, metabolites, generally]), verbo([found]), complemento([in, the, 'Asteraceae', family])]). relacion([sujeto(['Anti-tumour', and, 'anti-migraine', 'effects,', an, allergenic, 'agent,', an, inhibitor, of, smooth, muscle, cells, and, of, meristematic, cell, proliferation, are, only, a, few, of, the, most, commonly]), verbo([reported]), complemento([activities, of, 'STLs'])]). relacion([sujeto(['In', 'amphibians,', fully, grown, ovarian, oocytes, are]), verbo([arrested]), complemento([at, the, beginning, of, meiosis, 'I'])]). relacion([sujeto(['Under', stimulus, with, 'progesterone,', this, meiotic]), verbo([arrest]), complemento([is, released, and, meiosis, progresses, to, metaphase, 'II,', a, process, known, as, oocyte, maturation])]). relacion([sujeto(['It']), verbo([has]), complemento([been, also, shown, that, 'DhL', and, its, 11, ',', 13, -, dihydroderivative, '(', 2, 'H-DhL;', a, mixture, of, epimers, at, 'C-11)', act, as, blockers, of, the, resumption, of, meiosis, in, fully, grown, ovarian, oocytes, from, the, amphibian, 'Rhinella', arenarum, '(', formerly, classified, as, 'Bufo', 'arenarum)'])]). relacion([sujeto(['It', was]), verbo([found]), complemento([that, the, inhibitory, effect, on, meiosis, resumption, is, greater, when, the, lactone, has, two, potentially, reactive, 'centres,', either, a, 'α,β-α\',β\'-diunsaturated', cyclopentanone, moiety, or, an, epoxide, group, plus, an, 'exo-methylene-γ-lactone', function])]). relacion([sujeto(['According', to, section, 129, of, the, 'Act', a, child, may, consent, to, his, or, her, own, medical, treatment]), verbo([provided]), complemento([that, he, or, she, is, over, the, age, of, 12, &, 'nbsp;years', and, is, of, sufficient, maturity, and, decisional, capacity, to, understand, the, various, implications, of, the, treatment, including, the, risks, and, benefits, thereof])]). relacion([sujeto(['However,', the, 'Act', does, not]), verbo([provide]), complemento([a, definition, for, what, qualifies, as, '\'', sufficient, 'maturity\'', nor, does, it, stipulate, how, health, professionals, ought, to, assess, the, decisional, capacity, of, a, child])]). relacion([sujeto(['The', 'Western', liberal, notion, of, autonomy, may, not, necessarily]), verbo([find]), complemento([equal, prominence, in, the, mores, of, people, with, a, different, worldview])]). relacion([sujeto(['However,', contrary, to, the, traditional, 'Western', notion, of, individual, autonomous, persons, 'African', societies, hold, a, communalistic, notion, of, person, hence, there, is, less, regard, for, individual, autonomy, and, rights, with, more, emphasis, on, the, communal, good, and]), verbo([maintaining]), complemento([the, continuity, of, relationships, and, interdependencies, shared, within, a, community])]). relacion([sujeto(['It', seems, reasonable, to]), verbo([suggest]), complemento([a, move, away, from, a, general, legal, age, of, consent, for, medical, treatment, toward, more, 'individualised,', 'context-specific', approaches, in, determining, the, maturity, of, a, child, patient, to, consent, to, medical, treatment])]). relacion([sujeto(['Perhaps,', 'decision-making', with, respect, to, consent, to, the, medical, treatment, of, a, child, belonging, to, a, traditional, 'African', community, where, the, notion, of, a, person, is, embedded, in, communitarianism, ought, to]), verbo([involve]), complemento([the, 'child\'s', 'parents/guardians/caregivers', where, possible, provided, that, the, best, interests, of, the, child, are, awarded, priority])]). relacion([sujeto(['Mammalian', genomes, are, pervasively]), verbo([transcribed]), complemento([to, produce, thousands, of, long, 'non-coding', 'RNAs', '(', 'lncRNAs)'])]). relacion([sujeto(['A', few, of, these, lncRNAs]), verbo([have]), complemento([been, shown, to, recruit, regulatory, complexes, through, 'RNA-protein', interactions, to, influence, the, expression, of, nearby, 'genes,', and, it, has, been, suggested, that, many, other, lncRNAs, can, also, act, as, local, regulators])]). relacion([sujeto(['However,', these, correlations]), verbo([have]), complemento([been, challenging, to, dissect, and, could, alternatively, result, from, processes, that, are, not, mediated, by, the, lncRNA, transcripts, themselves])]). relacion([sujeto(['For', 'example,', some, gene, promoters]), verbo([have]), complemento([been, proposed, to, have, dual, functions, as, 'enhancers,', and, the, process, of, transcription, itself, may, contribute, to, gene, regulation, by, recruiting, activating, factors, or, remodelling, nucleosomes])]). relacion([sujeto(['Here', we, use, genetic, manipulation, in, mouse, cell, lines, to, dissect, 12, genomic, loci, that, produce, lncRNAs, and]), verbo([find]), complemento([that, 5, of, these, loci, influence, the, expression, of, a, neighbouring, gene, in, cis])]). relacion([sujeto(['Notably,', none, of, these, effects]), verbo([requires]), complemento([the, specific, lncRNA, transcripts, themselves, and, instead, involves, general, processes, associated, with, their, 'production,', including, 'enhancer-like', activity, of, gene, 'promoters,', the, process, of, 'transcription,', and, the, splicing, of, the, transcript])]). relacion([sujeto(['Furthermore,', such, effects, are, not, limited, to, lncRNA, 'loci:', we]), verbo([find]), complemento([that, four, out, of, six, 'protein-coding', loci, also, influence, the, expression, of, a, neighbour])]). relacion([sujeto(['These', results, demonstrate, that, 'cross-talk', among, neighbouring, genes, is, a, prevalent, phenomenon, that, can]), verbo([involve]), complemento([multiple, mechanisms, and, 'cis-regulatory', 'signals,', including, a, role, for, 'RNA', splice, sites])]). relacion([sujeto(['Hsp70', performs, a, plethora, of, 'tasks,', including, folding, 'assistance,', protection, against, 'aggregation,', protein, 'trafficking,', and, enzyme, activity, 'regulation,', and]), verbo([interacts]), complemento([with, 'non-folded', 'chains,', as, well, as, 'near-native,', 'misfolded,', and, aggregated, proteins])]). relacion([sujeto(['Hsp70', is, thought, to, achieve, its, many, physiological, roles, by]), verbo([binding]), complemento([peptide, segments, that, extend, from, these, different, protein, conformers, within, a, groove, that, can, be, covered, by, an, 'ATP-driven', helical, lid])]). relacion([sujeto(['However,', it]), verbo([has]), complemento([been, difficult, to, test, directly, how, 'Hsp70', interacts, with, protein, substrates, in, different, stages, of, folding, and, how, it, affects, their, structure])]). relacion([sujeto(['Here,', using, optical, 'tweezers,', we, show, that, the, bacterial, 'Hsp70', homologue, '(', 'DnaK)']), verbo([binds]), complemento([and, stabilizes, not, only, extended, peptide, 'segments,', but, also, partially, folded, and, 'near-native', protein, structures])]). relacion([sujeto(['The', 'Hsp70', lid, and, groove]), verbo([act]), complemento([synergistically, when, stabilizing, folded, 'structures:', stabilization, is, abolished, when, the, lid, is, truncated, and, less, efficient, when, the, groove, is, mutated])]). relacion([sujeto(['The', diversity, of]), verbo([binding]), complemento([modes, has, important, 'consequences:', 'Hsp70', can, both, stabilize, and, destabilize, folded, 'structures,', in, a, 'nucleotide-regulated', 'manner;', like, 'Hsp90', and, 'GroEL,', 'Hsp70', can, affect, the, late, stages, of, protein, 'folding;', and, 'Hsp70', can, suppress, aggregation, by, protecting, partially, folded, structures, as, well, as, unfolded, protein, chains])]). relacion([sujeto(['Nanowire', networks]), verbo([act]), complemento([as, 'self-healing', smart, 'materials,', whose, sheet, resistance, can, be, tuned, via, an, externally, applied, voltage, stimulus])]). relacion([sujeto(['While', most, network, studies]), verbo([have]), complemento([been, performed, on, expensive, noble, metal, nanowires, like, 'silver,', networks, of, inexpensive, nickel, nanowires, with, a, nickel, oxide, coating, can, also, demonstrate, resistive, 'switching,', a, common, feature, of, metal, oxides, with, filamentary, conduction])]). relacion([sujeto(['However,', networks, made, from, solely, nickel, nanowires]), verbo([have]), complemento([high, operation, voltages, which, prohibit, 'large-scale', material, applications])]). relacion([sujeto(['Small', percentages, of, silver, 'nanowires,', below, the, percolation, 'threshold,']), verbo([induce]), complemento([these, changes, in, electrical, 'behaviour,', even, for, low, area, coverage, and, hence, very, transparent, films])]). relacion([sujeto(['Silver', nanowires]), verbo([act]), complemento([as, current, 'concentrators,', amplifying, conductivity, locally, as, shown, in, our, computational, dynamical, activation, framework, for, networks, of, junctions])]). relacion([sujeto(['These', results, demonstrate, that, a, heterogeneous, nanowire, network, can]), verbo([act]), complemento([as, a, 'cost-effective', adaptive, material, with, minimal, use, of, noble, metal, 'nanowires,', without, losing, memristive, behaviour, that, is, essential, for, smart, sensing, and, neuromorphic, applications])]). relacion([sujeto(['Targeted', delivery, of, cytotoxic, drugs, to, tumour, tissue]), verbo([has]), complemento([great, importance, for, successful, chemotherapy])]). relacion([sujeto(['The', aim, of, this, work, was, to, prepare, a, novel, hyaluronic, acid, '(', 'HA)', based, legumain, sensitive, nanogel, for, the, delivery, of, doxorubicin, with, a, high]), verbo([targeting]), complemento([efficiency, both, in, vitro, and, in, vivo])]). relacion([sujeto(['Doxorubicin']), verbo([released]), complemento([in, the, tumour, tissue, is, sustained, thanks, to, the, combined, action, of, legumain, and, 'hyaluronidase,', which, are, both, overexpressed, in, tumour, tissues])]). relacion([sujeto(['Hyaluronic', acid, could]), verbo([act]), complemento([as, a, targeting, agent, to, 'CD44', '(', 'HA', 'receptor),', which, further, improved, the, in, vivo, target, effect, and, enhanced, in, vitro, cellular, uptake])]). relacion([sujeto(['The', 'European', 'Union', and, the, 'Organization', for, 'Economic', 'Cooperation', and, 'Development']), verbo([have]), complemento([argued, for, open, access, '(', 'OA)', to, scientific, data, for, all, publicly, funded, research, by, 2020, with, a, similar, initiative, in, the, 'USA', via, the, 'Fair', 'Access', to, 'Science', and, 'Technology', 'Research', 'Act', '(', 'FASTR)'])]). relacion([sujeto(['If', the, products, of, science, are, not, openly, available, then, it, can, be, argued, that, the, norms, of, science, as, defined, by, 'Merton', including, &, 'quot;universalism"', and, &, 'quot;communalism"']), verbo([have]), complemento([yet, to, be, accomplished])]). relacion([sujeto(['These', systems, often]), verbo([retain]), complemento([particulate, 'P', 'well,', whereas, the, retention, of, dissolved, 'P', is, less, efficient, and, might, require, addition, of, 'P', adsorbents])]). relacion([sujeto(['The', study, underlines, that, waste, products, may]), verbo([act]), complemento([as, potentially, effective, 'P', adsorbers, at, environmentally, relevant, 'P', levels])]). relacion([sujeto(['University', officials, agreed, to]), verbo([act]), complemento([only, after, a, scathing, investigation, by, 'Minnesota', 'Office', of, the, 'Legislative', 'Auditor', found, damning, evidence, of, coerced, 'recruitment,', inadequate, clinical, 'care,', superficial, research, 'oversight,', a, web, of, 'serious,', disturbing, conflicts, of, 'interest,', and, a, pattern, of, misleading, public, statements, by, university, officials, aimed, at, deflecting, scrutiny])]). relacion([sujeto(['In', this, 'article,', 'I', examine, the, larger, institutional, factors]), verbo([leading]), complemento([up, to, 'Markingson\'s', suicide, and, prevented, corrective, action, for, so, long])]). relacion([sujeto(['Interaction', of, advanced, glycation, end, products, '(', 'AGEs)', with, its, 'cell-bound', receptor, '(', 'RAGE)', results, in, cell, dysfunction, through, activation, of]), verbo([nuclear]), complemento([factor, 'kappa-B,', increase, in, expression, and, release, of, inflammatory, 'cytokines,', and, generation, of, oxygen, radicals])]). relacion([sujeto(['Circulating', soluble, 'receptors,', soluble, receptor, '(', 'sRAGE),', endogenous, secretory, receptor, '(', 'esRAGE)', and, cleaved, receptor, '(', 'cRGAE)']), verbo([act]), complemento([as, decoy, for, 'RAGE', ligands, and, thus, have, cytoprotective, effects])]). relacion([sujeto(['Low', levels, of, sRAGE, and, esRAGE]), verbo([have]), complemento([been, proposed, as, biomarkers, for, many, diseases])]). relacion([sujeto(['It', is, possible, that]), verbo([increases]), complemento([in, levels, of, 'AGEs', are, greater, than, increases, in, the, levels, of, soluble, receptors, in, these, two, diseases])]). relacion([sujeto(['Some', new, parameters]), verbo([have]), complemento([to, be, used, which, could, be, an, universal, biomarkers, for, cell, dysfunction])]). relacion([sujeto(['It', is, hypothesized, that]), verbo([increases]), complemento([in, serum, levels, of, 'AGEs', are, greater, than, the, increases, in, the, soluble, 'receptors,', and, that, the, levels, of, 'AGEs', is, correlated, with, soluble, receptors, and, that, the, ratios, of, 'AGEs/sRAGE,', 'AGEs/esRAGE', and, 'AGEs/cRAGE', are, elevated, in, patients, with, 'end-stage', renal, disease, '(', 'ESRD)', and, would, serve, as, an, universal, risk, marker, for, 'ESRD'])]). relacion([sujeto(['Brown', adipose, tissue, '(', 'BAT)', is, the, main, site, of, adaptive, thermogenesis, and, experimental, studies]), verbo([have]), complemento([associated, 'BAT', activity, with, protection, against, obesity, and, metabolic, 'diseases,', such, as, type, 2, diabetes, mellitus, and, dyslipidaemia])]). relacion([sujeto(['The', ability, of, 'BAT', to, protect, against, chronic, metabolic, disease]), verbo([has]), complemento([traditionally, been, attributed, to, its, capacity, to, utilize, glucose, and, lipids, for, thermogenesis])]). relacion([sujeto(['However,', 'BAT', might, also]), verbo([have]), complemento([a, secretory, 'role,', which, could, contribute, to, the, systemic, consequences, of, 'BAT', activity])]). relacion([sujeto(['Several', 'BAT-derived', molecules, that]), verbo([act]), complemento([in, a, paracrine, or, autocrine, manner, have, been, identified])]). relacion([sujeto(['Most', of, these, factors]), verbo([promote]), complemento([hypertrophy, and, hyperplasia, of, 'BAT,', 'vascularization,', innervation, and, blood, 'flow,', processes, that, are, all, associated, with, 'BAT', recruitment, when, thermogenic, activity, is, enhanced])]). relacion([sujeto(['Additionally,', 'BAT', can]), verbo([release]), complemento([regulatory, molecules, that, act, on, other, tissues, and, organs])]). relacion([sujeto(['This', secretory, capacity, of, 'BAT', is, thought, to, be]), verbo([involved]), complemento([in, the, beneficial, effects, of, 'BAT', transplantation, in, rodents])]). relacion([sujeto(['In', this, 'Review,', we, discuss, the, current, understanding, of, the, regulatory, molecules, '(', the, 'so-called', brown, adipokines, or, 'batokines)', that, are]), verbo([released]), complemento([by, 'BAT', that, influence, systemic, metabolism, and, convey, the, beneficial, metabolic, effects, of, 'BAT', activation])]). relacion([sujeto(['The', identification, of, such, adipokines, might, also, direct, drug, discovery, approaches, for, managing, obesity, and, its]), verbo([associated]), complemento([chronic, metabolic, diseases])]). relacion([sujeto(['Gut', bacteria, depend, fully, on, their, host, for]), verbo([providing]), complemento([the, nutrients, necessary, for, their, growth])]). relacion([sujeto(['The', intrinsic, ability, of, bacteria, to]), verbo([regulate]), complemento([their, growth, and, to, maintain, their, population, within, the, gut, suggests, that, gut, bacteria, can, interfere, with, molecular, pathways, controlling, energy, balance, in, the, host])]). relacion([sujeto(['The', current, model, of, appetite, control, is, based, mainly, on, 'gut-brain', signalling, and, the, 'animal\'s', own, needs, to]), verbo([maintain]), complemento([energy, 'homeostasis;', an, alternative, model, might, also, involve, 'bacteria-host', communications])]). relacion([sujeto(['Several', bacterial, components, and, metabolites]), verbo([have]), complemento([been, shown, to, stimulate, intestinal, satiety, 'pathways;', at, the, same, 'time,', their, production, depends, on, bacterial, growth, cycles])]). relacion([sujeto(['Indeed,', several, bacterial, products, are, detected, in, the, systemic, 'circulation,', which, might]), verbo([act]), complemento([directly, on, hypothalamic, neurons])]). relacion([sujeto(['Chromatin', modifications, shape, cell, heterogeneity, by]), verbo([activating]), complemento([and, repressing, defined, sets, of, genes, involved, in, cell, 'proliferation,', differentiation, and, development])]). relacion([sujeto(['Polycomb-repressive', complexes, '(', 'PRCs)']), verbo([act]), complemento([synergistically, during, development, and, differentiation, by, maintaining, transcriptional, repression, of, common, genes])]). relacion([sujeto(['Here,', we, show, that, in, the, intestinal, epithelium, 'PRC2', is]), verbo([required]), complemento([to, sustain, progenitor, cell, proliferation, and, the, correct, balance, between, secretory, and, absorptive, lineage, differentiation, programs])]). relacion([sujeto(['Using', genetic, 'models,', we, show, that, 'PRC2', activity, is, largely, dispensable, for, intestinal, stem, cell, maintenance, but, is, strictly]), verbo([required]), complemento([for, 'radiation-induced', regeneration, by, preventing, 'Cdkn2a', transcription])]). relacion([sujeto(['Combining', these, models, with, genomewide, molecular, 'analysis,', we, further, demonstrate, that, preferential, accumulation, of, secretory, cells, does, not, result, from, impaired, proliferation, of, progenitor, cells]), verbo([induced]), complemento([by, 'Cdkn2a', activation, but, rather, from, direct, regulation, of, transcription, factors, responsible, for, secretory, lineage, commitment])]). relacion([sujeto(['Silver', nanoparticles, '(', 'AgNPs)']), verbo([have]), complemento([antimicrobial, and, insecticidal, properties, and, they, have, been, considered, for, their, potential, use, as, insecticides])]). relacion([sujeto(['While', they, 'do,', 'indeed,', kill, some, 'insects,', two, broader, issues]), verbo([have]), complemento([not, been, considered, in, a, critical, way])]). relacion([sujeto(['First,']), verbo([reports]), complemento([of, 'insect-lethal', 'AgNPs', are, often, based, on, simplistic, methods, that, yield, nanoparticles, of, nonuniform, shapes, and, 'sizes,', leaving, questions, about, the, precise, treatments, test, insects, experienced])]). relacion([sujeto(['We', assessed, the, influence, of, 'AgNPs', on, life, history, parameters, of, two, agricultural, pest, insect, 'species,', 'Heliothis', virescens, '(', tobacco, 'budworm)', and, 'Trichoplusia', ni, '(', cabbage, 'looper)', and, a, beneficial, predatory, insect, 'species,', 'Podisus', maculiventris, '(', spined, soldier, 'bug),', all, of, which]), verbo([act]), complemento([in, agroecosystems])]). relacion([sujeto(['Rearing', the, two, pest, species, on, standard, media, amended, with, 'AgNPs']), verbo([led]), complemento([to, negligible, influence, on, developmental, 'times,', pupal, 'weights,', and, adult, 'emergence,', 'however,', they, led, to, retarded, 'development,', reductions, in, adult, weight, and, 'fecundity,', and, increased, mortality, in, the, predator])]). relacion([sujeto(['These', negative, effects, on, the, beneficial, 'species,', if, also, true, for, other, beneficial, insect, 'species,', would]), verbo([have]), complemento([substantial, negative, implications, for, continued, development, of, 'AgNPs', for, insect, pest, management, programs])]). relacion([sujeto(['In', 'Atlanta,', 'GA,', substantial, 'WNV', presence, in, hosts, and, vectors]), verbo([has]), complemento([not, resulted, in, the, human, disease, burden, observed, in, cities, with, similar, infection, pressure])]). relacion([sujeto(['We', therefore, rule, out, 'American', robins, as, superspreaders, in, the, 'Atlanta', area, and]), verbo([suggest]), complemento([instead, that, northern, cardinals, and, mimids, act, as, 'WNV', &, 'quot;supersuppressor"', 'species,', which, slow, 'WNV', transmission, by, drawing, many, infectious, bites, during, the, critical, virus, amplification, 'period,', yet, failing, to, amplify, transmission, due, to, low, host, competencies])]). relacion([sujeto(['Of', particular, 'interest,', urban, forest, patches]), verbo([provide]), complemento([spillover, protection, by, increasing, the, 'WNV', amplification, fraction, on, supersuppressor, species])]). relacion([sujeto(['The', testes, are, one, of, the, most, delicate, organs, in, the, male, body, and, highly, susceptible, to, the, exogenous, influences, capable, of]), verbo([inducing]), complemento([cell, damage])]). relacion([sujeto(['The', present, work, aimed, to, systematically, review, the, available, information, about, the, different, endogenous, factors, '(', hormonal, and, 'nonhormonal)', that, may]), verbo([have]), complemento([protective, or, advantageous, properties, on, the, recovery, of, male, reproductive, function, after, gonadal, injury])]). relacion([sujeto(['Furthermore,', the, perspective, that, these, endogenous, molecules, could]), verbo([act]), complemento([as, cryoprotectants, to, improve, the, quality, of, cryopreserved, semen, samples, was, also, discussed])]). relacion([sujeto(['Previous', studies]), verbo([have]), complemento([demonstrated, that, melatonin, administration, improves, spatial, learning, and, memory, and, hippocampal, 'long-term', potentiation, in, the, adult, 'Ts65Dn', '(', 'TS)', 'mouse,', a, model, of, 'Down', syndrome, '(', 'DS)'])]). relacion([sujeto(['Melatonin', treatment]), verbo([induced]), complemento([antioxidant, and, antiaging, effects, in, the, hippocampus, of, adult, 'TS', mice])]). relacion([sujeto(['Although', melatonin, administration, did, not]), verbo([regulate]), complemento([the, activities, of, the, main, antioxidant, enzymes, '(', superoxide, 'dismutase,', 'catalase,', glutathione, 'peroxidase,', glutathione, 'reductase,', and, glutathione, 'S-transferase)', in, the, cortex, or, 'hippocampus,', melatonin, decreased, protein, and, lipid, oxidative, damage, by, reducing, the, thiobarbituric, acid, reactive, substances, '(', 'TBARS)', and, protein, carbonyls, '(', 'PC)', levels, in, the, 'TS', hippocampus, due, to, its, ability, to, act, as, a, free, radical, scavenger])]). relacion([sujeto(['Consistent', with, this, reduction, in, oxidative, 'stress,', melatonin, also]), verbo([decreased]), complemento([hippocampal, senescence, in, 'TS', animals, by, normalizing, the, density, of, 'senescence-associated', 'β-galactosidase', positive, cells, in, the, hippocampus])]). relacion([sujeto(['Pigs']), verbo([have]), complemento([been, reported, to, act, as, a, reservoir, for, zoonotic, 'viruses,', sometimes, emerging, 'ones,', and, epidemiological, studies, have, shown, direct, links, between, the, consumption, of, uncooked, pork, offal, and, cases, of, hepatitis, caused, by, the, hepatitis, 'E', virus, '(', 'HEV)', genotype, 3, in, humans])]). relacion([sujeto(['The', presence, of, 'HEV', in, swine, herds]), verbo([has]), complemento([been, 'reported,', but, its, dissemination, in, pork, production, environments, is, still, unknown])]). relacion([sujeto(['MGRN1', ubiquitinates, and]), verbo([regulates]), complemento([tumour, susceptibility, gene, 101, '(', 'TSG101),', a, central, component, of, the, endosomal, trafficking, machinery])]). relacion([sujeto(['As']), verbo([loss]), complemento([of, 'MGRN1', is, predicted, to, cause, partial, 'TSG101', 'loss-of-function,', we, hypothesised, that, 'CNS', vacuolation, in, 'Mgrn1', null, mice, may, be, caused, by, the, accumulation, of, 'multi-cisternal', 'endosome-like', '\'', class, 'E\'', vacuolar, protein, sorting, '(', 'vps)', compartments, similar, to, those, observed, in, 'Tsg101-depleted', cells, in, culture])]). relacion([sujeto(['Vacuoles', in, the, brains, of, mice, inoculated, with, 'Rocky', 'Mountain', 'Laboratory', '(', 'RML)', prions, did, not, label, with, these, 'markers,', indicating, a, different, 'origin,', consistent, with, previously, published, studies, that, indicate, 'RML', prions]), verbo([have]), complemento([a, primary, effect, on, neurons, and, cause, vacuolation, in, an, 'MGRN1-independent', manner])]). relacion([sujeto(['Oligodendroglial', deletion, of, 'Rab7,', which]), verbo([mediates]), complemento([late, 'endosome-to-lysosome', trafficking, and, 'autophagosome-lysosome', 'fusion,', did, not, cause, spongiform, change])]). relacion([sujeto(['Our', data]), verbo([suggest]), complemento([that, the, formation, of, 'multi-cisternal', '\'', class, 'E\'', vps, endosomal, structures, in, oligodendroglia, leads, to, vacuolation])]). relacion([sujeto(['This', work]), verbo([provides]), complemento([the, first, evidence, that, disrupting, 'multi-vesicular', body, formation, in, oligodendroglia, can, cause, white, matter, vacuolation, and, demyelination])]). relacion([sujeto(['HIV', is, known, to, hijack, the, endosomal, sorting, 'machinery,']), verbo([suggesting]), complemento([that, 'HIV', infection, of, the, 'CNS', may, also, act, through, this, pathway, to, cause, encephalopathy])]). relacion([sujeto(['This', article, discusses, 'Geiger\'s', review, of, 'empathy,']), verbo([expressed]), complemento([in, a, lecture, at, the, 'IV', 'German', 'Congress', of, 'Experimental', 'Psychology', in, 1910])]). relacion([sujeto(['(', 'PsycINFO', 'Database', 'Record', 'The', plasma, membrane, 'P-glycoprotein', '(', 'Pgp)', is, an, efflux, transporter]), verbo([involved]), complemento([in, multidrug, resistance, and, in, the, onset, of, neurodegenerative, disease])]). relacion([sujeto(['The', synthetic, procedure, and, the, quality, control, of, the, selected]), verbo([lead]), complemento(['compound,', '[', '(', 11, ')', 'C]AEPH-1,', were, set, up, and, optimized])]). relacion([sujeto(['The', biodistribution, and, the, dynamic, extraction, in]), verbo([target]), complemento([organs, of, '[', '(', 11, ')', 'C]AEPH-1', were, studied, in, vivo, by, 'PET', in, healthy, rats, at, baseline, and, after, 'pre-treatment', with, a, 'Pgp', inhibitor, '(', 'tariquidar)'])]). relacion([sujeto(['An', adequate, stability, for, in, vivo, 'studies,', as, well, as, a, high, activity, of, '[', '(', 11, ')', 'C]AEPH-1', in, intestine, and, barrier, 'tissues,']), verbo([has]), complemento([been, demonstrated])]). relacion([sujeto(['Results', of, the, blockade, study, showed, a]), verbo([decrease]), complemento([of, uptake, after, the, 'pre-treatment,', indicating, a, behavior, attributable, to, a, 'Pgp', ligand])]). relacion([sujeto(['The', suitable, pharmacokinetics, and, the, specificity, tested, in, the, 'pre-treated', animals]), verbo([have]), complemento([indicated, the, potentiality, of, this, 'AEPH', derivative, to, act, as, 'Pgp', 'ligand,', providing, new, opportunities, for, further, studies, on, expression, and, function, of, this, important, efflux, transporter, in, the, fields, of, neurology, and, oncology])]). relacion([sujeto(['Secondary', analysis, was, undertaken, on, data, from, a, multicentre, cluster, randomised, controlled, trial, in, which, 15, clinicians, were, randomly, assigned, to, refer, eligible, patients, to, an, 'exercise training', intervention, '(', n, =, 8, ')', or, to]), verbo([provide]), complemento([usual, care, '(', n, =, 7, ')'])]). relacion([sujeto(['A', significant, difference, '(', unadjusted, for, 'multiplicity)', in, favour, of, men, in, the, intervention, was, also]), verbo([found]), complemento([for, resting, heart, rate, '(', 'M', diff, =, -, 3.76, 'beats/min,', p, =, 0.034, ')'])]). relacion([sujeto(['Men', with, prostate, cancer, who]), verbo([act]), complemento([upon, clinician, referrals, to, 'community-based', exercise, training, programs, can, improve, their, 'strength,', physical, 'functioning,', 'and,', 'potentially,', cardiovascular, 'health,', irrespective, of, whether, or, not, they, are, treated, with, 'ADT'])]). relacion([sujeto(['In', 'contrast,', their, influence, should, be, overadditive, if, they]), verbo([act]), complemento([at, the, same, processing, level, in, spelling, to, 'dictation,', namely, the, spoken, word, recognition, level])]). relacion([sujeto(['We']), verbo([found]), complemento([that, both, factors, had, a, reliable, influence, on, the, spelling, latencies, but, did, not, interact])]). relacion([sujeto(['This']), verbo([finding]), complemento([is, in, line, with, an, orthographic, output, locus, hypothesis, of, word, frequency, effects, in, spelling, to, dictation])]). relacion([sujeto(['The', 'Medicare', 'Access', and, 'Children\'s', 'Health', 'Insurance', 'Program', 'Reauthorization', 'Act', represents, a, cohesive, movement, toward, 'value-based', payment, reform, and, contains, several, unchartered, rulings, that]), verbo([require]), complemento([detailed, attention, by, knee, surgeons])]). relacion([sujeto(['In', this, 'article,', we]), verbo([provide]), complemento([a, contextual, framework, of, health, care, legislation, that, has, led, to, the, formation, of, the, current, health, 'policy,', and, present, a, comprehensive, summary, and, update, on, the, 'Merit-Based', 'Incentive', 'Payment', 'Systems', and, 'Alternative', 'Payment', 'Models', reimbursement, models])]). relacion([sujeto(['It', is, known, that, 'miR-143']), verbo([participates]), complemento([in, the, development, of, various, tumor, progressions])]). relacion([sujeto(['Accordingly,', the, expression, levels, of, the, extracellular, signal]), verbo([regulated]), complemento([kinase, 5, '(', 'ERK5)', were, significantly, increased, in, spinal, 'GBM', tissues, and, cell, lines])]). relacion([sujeto(['Ectopic', expression, of, 'miR-143', in, 'U87', and, 'U251', cells, resulted, in]), verbo([decreased]), complemento([cell, growth, and, enhanced, cell, 'apoptosis,', and, inhibited, the, expression, of, 'epithelial-mesenchymal', transition, '(', 'EMT)', biomarkers])]). relacion([sujeto(['Further', study, characterized, the, 3, '\'', untranslated, region, '(', 3, '\'', -, 'UTR)', of, 'ERK5', gene, as, a, direct]), verbo([target]), complemento([of, 'miR-143', in, 'U87', and, 'U251', cells, as, determined, by, luciferase, reporter, assays])]). relacion([sujeto(['In', 'addition,', the, ectopic, expression, of, 'miR-143']), verbo([led]), complemento([to, the, 'down-regulation', of, epidermal, growth, factor, receptor, '(', 'EGFR),', while, the, 'over-expression', of, 'ERK5', reversed, the, 'miR-143-inhibited', 'EGFR', 'expression,', and, promoted, cell, growth, and, the, expression, of, 'EMT', biomarkers])]). relacion([sujeto(['In', 'conclusion,', this, study, demonstrated, that, 'miR-143', plays, a, crucial, role, in]), verbo([regulating]), complemento([the, 'EMT', of, 'GBM', by, directly, targeting, 'ERK5,', and, 'miR-143', may, act, as, a, potential, therapeutic, target, in, spinal, 'GBM', patients])]). relacion([sujeto(['In', this, 'study,', we]), verbo([reported]), complemento(['VOSL', '(', volatile, oil, from, 'Saussurea', lappa, 'root)', exhibits, potent, therapeutic, effect, on, 'SMMC-7721', xenografts, without, obvious, side, effects])]). relacion([sujeto(['In', the, in, vitro, 'experiments,', 'VOSL']), verbo([inhibited]), complemento(['HCC', cell, proliferation, by, arresting, cell, cycle, at, 'S', and, 'G2/M', 'phases,', and, induced, 'HCC', cell, apoptosis, by, activating, the, 'Caspase3', pathway])]). relacion([sujeto(['VOSL', also]), verbo([decreased]), complemento([the, capability, of, 'HCC', cell, migration, and, invasion, through, 'MMP-9', depression])]). relacion([sujeto(['Moreover,', mechanistic, study, indicated, that, 'VOSL', can]), verbo([act]), complemento([as, an, epithelial, growth, factor, receptor, '(', 'EGFR)', inhibitor, to, suppress, 'EGFR', activation, and, then, to, suppress, its, downstream, 'MEK/P38', and, 'PI3-K/Akt', pathways])]). relacion([sujeto(['These', results]), verbo([suggested]), complemento([that, 'VOSL', may, be, a, novel, 'anti-HCC', drug, candidate])]). relacion([sujeto(['Membrane', proteins]), verbo([act]), complemento([as, a, central, interface, between, the, extracellular, environment, and, the, intracellular, response, and, as, such, represent, one, of, the, most, important, classes, of, drug, targets])]). relacion([sujeto(['Atomic', force, microscopy, '(', 'AFM)', and, force, spectroscopy]), verbo([have]), complemento([the, intrinsic, capabilities, of, investigating, these, properties, in, a, 'near-native', setting])]). relacion([sujeto(['Alternatively,', model, membrane, 'systems,', such, as, tethered, bilayer, 'membranes,']), verbo([have]), complemento([been, developed, for, 'surface-dependent', techniques])]). relacion([sujeto(['While', these, setups, can]), verbo([provide]), complemento([a, more, native, 'environment,', data, analysis, may, be, complicated, by, the, normally, found, statistical, orientation, of, the, reconstituted, protein, in, the, model, membrane])]). relacion([sujeto(['We']), verbo([have]), complemento([developed, a, model, membrane, system, that, enables, the, study, of, membrane, proteins, in, a, defined, orientation, by, 'single-molecule', force, spectroscopy])]). relacion([sujeto(['Our', approach, is, demonstrated, using, 'cell-free']), verbo([expressed]), complemento([bacteriorhodopsin, coupled, to, a, quartz, glass, surface, in, a, defined, orientation, through, a, protein, anchor, and, reconstituted, inside, an, artificial, membrane, system])]). relacion([sujeto(['Uncontrolled', hemorrhage, is, a]), verbo([leading]), complemento([cause, of, mortality, following, trauma, accounting, for, up, to, 40, '%', of, deaths])]). relacion([sujeto(['Recently,', the, superiority, of, thrombelastography, '(', 'TEG)-guided', resuscitation, over, strategies, guided, by, conventional, clotting, assays, '(', 'CCA)']), verbo([has]), complemento([been, established])]). relacion([sujeto(['ROC', analysis, of, 'r-TEG', yielded, areas, under, the, curve, '(', 'AUC)', greater, than, 70, '%', for, all, outputs, with, respect, to, both, transfusion, thresholds, 'considered,', with, exception, of]), verbo([activated]), complemento([clotting, time, '(', 'ACT)', and, lysis, at, 30, minutes, '(', 'LY30)', for, &, 'gt;', 4, 'U', 'RBC', in, any, hour, in, the, first, 6, hours])]). relacion([sujeto(['Through', 'ROC', analysis, of, prospective, 'TEG', 'data,', we]), verbo([have]), complemento([identified, optimal, thresholds, to, guide, hemostatic, resuscitation])]). relacion([sujeto(['As', a, result, of, the, 'Affordable', 'Care', 'Act,']), verbo([increases]), complemento([in, aging, 'populations,', and, advances, in, 'technologies,', there, is, a, critical, need, for, highly, 'qualified,', competent, home, healthcare, nurses])]). relacion([sujeto(['According', to, the, 'Joint', 'Commission\'s', 'Human', 'Resource', 'Standard,', home, healthcare, nurses, must, demonstrate, their, competency, at, least, every, 3, years, by]), verbo([participating]), complemento([in, 'in-service', education, '(', ')'])]). relacion([sujeto(['A', review, of, several, states, healthcare, regulatory, 'rules-specifically', 'California,', 'New', 'York,', 'Nevada,', and, 'Virginia,']), verbo([reveals]), complemento([no, mandates, for, home, healthcare, nurses, to, demonstrate, competencies, for, skills, specific, for, home, healthcare, nursing])]). relacion([sujeto(['This', article, will, discuss, how, a, simulation, tool, kit, can, be, the, format, by, which, 'HHA', can]), verbo([enhance]), complemento([the, knowledge, and, skills, of, their, 'nurses,', and, promote, effective, health, outcomes, and, protect, the, public, from, harm])]). relacion([sujeto(['This', article, deals, with, compulsory, licensing, scenarios, in, 'India,']), verbo([provides]), complemento([a, background, of, relevant, provisions, in, the, 'Patents', 'Act', and, examines, how, these, provisions, are, 'Trade-Related', 'Aspects', of, 'Intellectual', 'Property', 'Rights', compliant])]). relacion([sujeto(['This', article, further, discusses, the, procedure, followed, by, 'India', in, granting, a, compulsory, 'license,']), verbo([provides]), complemento([an, overview, of, compulsory, license, applications, filed, in, 'India', to, date, and, judicial, precedence, regarding, the, same])]). relacion([sujeto(['The', 'Adverse', 'Outcome', 'Pathway', '(', 'AOP)', concept, is, expected, to, guide, risk, assessors, in, their, work, to, use, all, existing, information, on, the, effects, of, chemicals, on, humans, and, 'wildlife,', and, to]), verbo([target]), complemento([the, generation, of, additional, information, to, the, regulatory, objective])]). relacion([sujeto(['AOPs', will, therefore, be, used, in, the, 'Organisation', for, 'Economic', 'Co-operation', and, 'Development', '(', 'OECD)', chemical, safety, 'programme,', as, underlying, scientific, rationales, for, the, development, of, alternative, methods, for, hazard, 'assessment,', such, as, 'read-across,', in, vitro, test, methods, or, the, development, of, integrated, testing, strategies, that]), verbo([have]), complemento([the, potential, to, replace, animal, tests])]). relacion([sujeto(['As', a, 'proof-of-concept,', the, 'OECD']), verbo([has]), complemento([developed, an, 'AOP', for, skin, 'sensitisation,', and, as, a, 'follow-up', 'has:', 'a)', implemented, the, 'AOP', into, the, 'OECD', 'QSAR', 'Toolbox,', so, that, information, related, to, the, 'Key', 'Events', '(', 'KEs)', in, the, 'AOP', can, be, used, to, group, chemicals, that, are, expected, to, act, by, the, same, mechanism, and, hence, have, the, same, skin, sensitisation, 'potential;', 'b)', developed, alternative, test, methods, for, the, 'KEs,', so, that, ultimately, chemicals, can, be, tested, for, skin, sensitisation, without, the, use, of, animal, tests])]). relacion([sujeto(['Building', on, this, 'proof-of-concept,', the, 'OECD']), verbo([has]), complemento([launched, an, 'AOP', development, programme, with, a, first, batch, of, 'AOPs', published, in, 2016])]). relacion([sujeto(['However,', the, literature, on, early, warning, systems, '(', 'EWSs)']), verbo([provides]), complemento([limited, information, on, how, respecting, patient, preferences, can, be, incorporated, into, clinical, workflows])]). relacion([sujeto(['Our', workflows, take, local, resource, availability, into, account, and]), verbo([have]), complemento([been, well, received, by, 'hospitalists,', 'nurses,', and, families])]). relacion([sujeto(['Creation', of, a, palliative, care, response, arm, that, is, complementary, to, a, clinical, rescue, arm]), verbo([ensures]), complemento([that, patient, preferences, are, respected])]). relacion([sujeto(['Efforts', to, improve, outcomes, of, patients, who, deteriorate, outside, the, intensive, care, unit]), verbo([have]), complemento([included, the, use, of, rapid, response, teams, '(', 'RRTs)', as, well, as, manual, and, automated, prognostic, scores])]). relacion([sujeto(['Although', automated, early, warning, systems, '(', 'EWSs)', are, starting, to, enter, clinical, 'practice,', there, are, few]), verbo([reports]), complemento([describing, implementation, and, the, processes, required, to, integrate, early, warning, approaches, into, 'hospitalists\'', workflows])]). relacion([sujeto(['Our', basic, 'workflow,', which, relies, on, having, an, 'RRT', nurse, and, the, 'EWS\'s', 12, -, hour, outcome, time, 'frame,']), verbo([has]), complemento([been, accepted, by, clinicians, and, has, not, been, associated, with, patient, complaints])]). relacion([sujeto(['Sepsis', is, a]), verbo([leading]), complemento([cause, of, 'in-hospital', 'death,', and, evidence, suggests, a, higher, mortality, in, patients, presenting, with, sepsis, on, the, ward, compared, to, those, presenting, to, the, emergency, department])]). relacion([sujeto(['Ward', patients, who, develop, severe, sepsis, may]), verbo([have]), complemento([poor, outcomes, for, a, variety, of, 'reasons,', including, delayed, 'diagnosis,', lack, of, readily, available, 'staffing,', and, delayed, treatment])]). relacion([sujeto(['We']), verbo([report]), complemento([on, a, multihospital, quality, improvement, program, for, early, detection, and, treatment, of, sepsis, on, general, 'medical-surgical', wards])]). relacion([sujeto(['Based', on, our, 'experience,', we, recommend, a, stepwise, approach, to, implement, such, a, 'program:', '(', 1, ')', both, administrative, and, clinical, leadership, commit, to, a, common, 'goal;', '(', 2, ')', appoint, clinical, champions, and, give, them, authority, to, engage, other, clinicians, to, improve, timeliness, of, 'interventions;', '(', 3, ')', map, workflows, and, processes, to, rely, heavily, on, the, nursing, 'staff\'s', ability, to, evaluate, and]), verbo([report]), complemento([severe, sepsis, screening, 'results;', '(', 4, ')', if, 'available,', design, and, deploy, technology, with, the, assistance, of, clinical, informaticians, '(', 'eg,', to, enable, electronic, health, 'records-based', continuous, 'screening);', '(', 5, ')', to, determine, 'success,', consider, tracking, screening, compliance, and, 'process,', and, outcome, measures, such, as, length, of, stay, and, mortality])]). relacion([sujeto(['A', 'high-power', pulsed, 'Tm-doped', fiber, laser, operating, at, 1.94, &, 'nbsp;μm', with, a, temporal, duty, ratio, of, 30, '%', was, employed, as, a, pump, laser, to]), verbo([increase]), complemento([the, equivalent, incident, pump, power])]). relacion([sujeto(['A', piece, of, 150, &, 'nbsp;m', highly, 'GeO<sub>2</sub>-doped', silica, fiber, that]), verbo([provides]), complemento([a, strong, 'Raman', gain, and, random, distributed, feedbacks, was, used, to, act, as, the, gain, medium])]). relacion([sujeto(['Sinoatrial', node, myocytes, '(', 'SAMs)']), verbo([act]), complemento([as, the, natural, pacemakers, of, the, 'heart,', initiating, each, heart, beat, by, generating, spontaneous, action, potentials, '(', 'APs)'])]). relacion([sujeto(['However,', the, indistinct, 'anatomy,', complex, 'microdissection,', and, finicky, enzymatic, digestion, conditions]), verbo([have]), complemento([prevented, widespread, use, of, acutely, isolated, 'SAMs'])]). relacion([sujeto(['Here', we]), verbo([provide]), complemento([a, 'step-by-step', protocol, and, video, demonstration, for, the, isolation, of, 'SAMs', from, adult, mice])]). relacion([sujeto(['A', method, is, also, demonstrated, for]), verbo([maintaining]), complemento([adult, mouse, 'SAMs', in, vitro, and, for, expression, of, exogenous, proteins, via, adenoviral, infection])]). relacion([sujeto(['Data', from, the, 'National', 'Health', 'Interview', 'Survey,', 2013, -, 2015, '•', 'From', 2013, through, 2015, ',', the, percentage, of, adults, aged, 18, -, 64, who, were, uninsured, at, the, time, of, interview]), verbo([decreased]), complemento([for, poor, '(', 40.0, '%', to, 26.2, '%', ')', ',', 'near-poor', '(', 37.8, '%', to, 23.9, '%', ')', ',', and, 'not-poor', '(', 11.7, '%', to, 7.7, '%', ')', adults])]). relacion([sujeto(['•', 'The', percentage, of, adults, aged, 18, -, 64, who, had, a, usual, place, to, go, for, medical, care]), verbo([increased]), complemento([for, poor, '(', 66.9, '%', to, 73.6, '%', ')', and, 'near-poor', '(', 71.1, '%', to, 75.9, '%', ')', adults])]). relacion([sujeto(['•', 'The', percentage, of, adults, aged, 18, -, 64, who, had, seen, or, talked, to, a, health, professional, in, the, past, 12, months]), verbo([increased]), complemento([for, poor, '(', 73.2, '%', to, 75.8, '%', ')', and, 'near-poor', '(', 71.9, '%', to, 75.9, '%', ')', adults])]). relacion([sujeto(['•', 'The', percentage, of, adults, aged, 18, -, 64, who, did, not, obtain, needed, medical, care, due, to, cost, at, some, time, during, the, past, 12, months]), verbo([decreased]), complemento([for, poor, '(', 16.8, '%', to, 12.4, '%', ')', ',', 'near-poor', '(', 14.6, '%', to, 11.0, '%', ')', ',', and, 'not-poor', '(', 4.9, '%', to, 3.8, '%', ')', adults])]). relacion([sujeto(['Individuals', living, in, or, near, poverty, may]), verbo([have]), complemento([benefited, disproportionately, from, these, changes, given, their, lower, rates, of, health, insurance, coverage, '(', 1, ')'])]). relacion([sujeto(['The', 'Health', 'Information', 'Technology', for, 'Economic', and, 'Clinical', 'Health', 'Act', '(', 'HITECH)']), verbo([provides]), complemento([financial, incentives, to, eligible, providers, using, a, certified, electronic, health, record, '(', 'EHR)', system, '(', 1, ',', 2, ')'])]). relacion([sujeto(['A', federal, plan, to]), verbo([enhance]), complemento([the, 'nation\'s', health, information, technology, infrastructure, was, published, in, 2015, to, support, information, sharing, '(', 6, ',', 7, ')'])]). relacion([sujeto(['Therefore,', this]), verbo([report]), complemento([uses, the, 2015, 'National', 'Electronic', 'Health', 'Records', 'Survey', '(', 'NEHRS)', to, describe, the, extent, to, which, physicians, can, electronically, 'send,', 'receive,', 'integrate,', and, search, for, patient, health, information])]). relacion([sujeto(['Recently,', the, government]), verbo([has]), complemento([announced, a, plan, to, lift, this, ban])]). relacion([sujeto(['These', 'include:', why, is, such, therapy, 'mandatory?', 'What', are, the, indications, for, this, 'therapy,', and, what, are, the, 'mechanism(s)', of, 'actions?', 'What', types, of, cells, are]), verbo([involved]), complemento([and, what, are, their, routes, of, 'actions?', 'Finally,', what, is, known, about, the, 'safety?', 'In', 'general,', the, risks, associated, with, intravenous, administration, of, immunoregulatory, cell, products, are, similar, to, those, encountered, with, conventional, blood, transfusions])]). relacion([sujeto(['The', adverse, effects, of, immunosuppressive, 'drugs,', such, as, 'infections,', cardiovascular, 'disease,', metabolic, 'complications,', and, 'malignancies,', would, be]), verbo([decreased]), complemento([with, cell, therapy])]). relacion([sujeto(['Immunoregulatory', cells]), verbo([act]), complemento([when, necessary, and, through, multiple, mechanisms, through, different, targets])]). relacion([sujeto(['Immunoregulatory', cells, are, not, only, passive, inhibitors, such, as, 'drugs,', but, they]), verbo([have]), complemento([active, functions])]). relacion([sujeto(['Treatment', would, only, be, once, or, perhaps, a, few, times, but, not, 'indefinitely,', which, is, in, contrast, to, immunosuppressive, 'drugs;', 'therefore,', complications]), verbo([involving]), complemento([immunosuppressive, drugs, are, no, longer, present])]). relacion([sujeto(['Many', cell, types]), verbo([have]), complemento([being, investigated, as, potential, 'cell-based', immunotherapies, for, use, in, 'solid-organ', 'transplant,', including, mesenchymal, stromal, 'cells,', regulatory, 'macrophages,', tolerogenic, dendritic, 'cells,', regulatory, 'T', 'cells,', and, regulatory, 'B', cells])]). relacion([sujeto(['Statins']), verbo([induce]), complemento([apoptosis, of, tumor, cells, by, inhibiting, the, prenylation, of, small, 'G-proteins'])]). relacion([sujeto(['The', present, study, showed, that, the, induction, of, apoptosis, by, statins, in, four, different, human, head, and, neck, squamous, cell, carcinoma, '(', 'HNSCC)', cell, 'lines,', 'HSC-3,', 'HEp-2,', 'Ca9-22,', and, 'SAS', cells, was]), verbo([mediated]), complemento([by, increased, 'caspase-3', activity])]). relacion([sujeto(['Statins']), verbo([induced]), complemento([apoptosis, by, the, suppression, of, geranylgeranyl, pyrophosphate, biosynthesis])]). relacion([sujeto(['Furthermore,', statins]), verbo([decreased]), complemento([the, levels, of, phosphorylated, 'ERK', and, mTOR, by, inhibiting, the, membrane, localization, of, 'Ras', and, enhancing, 'Bim', expression, in, 'HSC-3', and, 'HEp-2', cells])]). relacion([sujeto(['We', also]), verbo([found]), complemento([that, in, all, the, cell, types, 'analyzed,', the, 'IC50', values, for, fluvastatin, and, simvastatin, were, highest, in, 'HEp-2', cells])]). relacion([sujeto(['Our', results, indicate, that, statins]), verbo([induce]), complemento([apoptosis, by, increasing, the, activation, of, 'caspase-3', and, by, enhancing, 'Bim', expression, through, inhibition, of, the, 'Ras/ERK', and, 'Ras/mTOR', pathways])]). relacion([sujeto(['Furthermore,', the, sensitivity, of, 'HNSCC', cells, to, statin, treatment, was, closely, related, to, 'Ras', expression, and, prenylation, 'levels,', indicating, that, statins, may]), verbo([act]), complemento([more, effectively, against, tumors, with, high, 'Ras', expression, and, 'Ras-variability'])]). relacion([sujeto(['To', examine, the, relationship, between, 'anti-Müllerian', hormone, '(', 'AMH)', and, the, severity, of, the, phenotype, of, patients, with, polycystic, ovary, syndrome, '(', 'PCOS)', and, whether, 'AMH', can]), verbo([act]), complemento([as, a, diagnostic, marker, for, 'PCOS?', 'A', prospective, diagnostic, utility, study, of, 'AMH', as, a, marker, of, 'PCOS'])]). relacion([sujeto(['A', consecutive, series, of, women, presenting, to, a, tertiary, infertility, clinic, '(', n, =, 164, ')', plus, a, second, series, of, women, prepared, for, assisted, conception, treatments, '(', n, =, 89, ')']), verbo([recruited]), complemento([between, 'June', 2012, and, 'May', 2013])]). relacion([sujeto(['Follicle', 'number,']), verbo([increasing]), complemento([cycle, length, and, evidence, of, hyperandrogenism, were, all, independently, associated, with, serum, 'AMH', concentration, '(', 'P', &, 'lt;', 0, '·01)'])]). relacion([sujeto(['Serum', 'AMH']), verbo([has]), complemento([the, capacity, to, act, as, a, diagnostic, test, for, 'PCOS'])]). relacion([sujeto(['A', facile, approach]), verbo([has]), complemento([been, developed, to, prepare, 'well-designed', 'MoS2-based', flexible, anisotropic, actuators, with, tunable, 'thermo-', and, 'photo-responses,', in, which, 'MoS2', nanosheets, act, as, the, photothermal, transduction, agents, and, enable, remote, and, precise, control, of, the, actuator, locomotion])]). relacion([sujeto(['Patients', with, eating, disorders, '(', 'EDs)', frequently]), verbo([report]), complemento([a, history, of, childhood, trauma, '(', 'CT)'])]). relacion([sujeto(['We', investigated, whether, certain, subtypes, of, 'CT', are]), verbo([associated]), complemento([with, more, severe, features, of, 'EDs,', independently, of, psychiatric, 'comorbidity,', and, whether, they, act, additively])]). relacion([sujeto(['The', clinical, features, were]), verbo([associated]), complemento([with, at, least, one, 'CT', subtype, '(', 'emotional,', sexual, or, physical, 'abuse,', emotional, 'neglect)'])]). relacion([sujeto(['A', 'dose-effect', relationship, characterised, the, number, of, 'CT', subtypes, and, the, severity, of, the, clinical, 'features,']), verbo([suggesting]), complemento([a, consistent, and, partly, independent, association, between, 'CT', and, more, severe, clinical, and, functional, characteristics, in, 'EDs'])]). relacion([sujeto(['Emotional', abuse, seems, to]), verbo([have]), complemento([the, most, specific, impact, on, 'ED', symptoms])]). relacion([sujeto(['Last,', not, all, 'CT', subtypes]), verbo([have]), complemento([the, same, impact, but, they, do, act, additively])]). relacion([sujeto(['Snake', venoms, are, natural, sources, of, biologically, active, molecules, that, are, able, to]), verbo([act]), complemento([selectively, and, specifically, on, different, cellular, 'targets,', modulating, physiological, functions])]). relacion([sujeto(['Thus,', these, 'mixtures,', composed, mainly, of, proteins, and, 'peptides,']), verbo([provide]), complemento([ample, and, challenging, opportunities, and, a, diversified, molecular, architecture, to, design, and, develop, tools, and, agents, of, scientific, and, therapeutic, interest])]). relacion([sujeto(['The', pharmaceutical, and, cosmetic, industries]), verbo([have]), complemento([recognized, the, huge, potential, of, these, privileged, frameworks, and, believe, them, to, be, a, promising, alternative, to, contemporary, drugs])]). relacion([sujeto(['A', number, of, natural, or, synthetic, peptides, from, snake, venoms]), verbo([have]), complemento([already, found, preclinical, or, clinical, applications, for, the, treatment, of, 'pain,', 'hypertension,', cardiovascular, diseases, and, aging, skin])]). relacion([sujeto(['A', 'well-known', example, is, 'captopril,', whose, natural, peptide, precursor, was, isolated, from, 'Bothrops', jararaca, snake, 'venom,', which, is, a, 'peptide-based', drug, that]), verbo([inhibits]), complemento([the, 'angiotensin-converting', 'enzyme,', producing, an, 'anti-hypertensive', effect])]). relacion([sujeto(['Heat', shock, proteins, '(', 'HSPs)', are, families, of, molecular, chaperones, that, play, important, homeostatic, functions, in, the, central, nervous, system, '(', 'CNS)', by]), verbo([preventing]), complemento([protein, 'misfolding,', promoting, degradation, of, improperly, folded, 'proteins,', and, protecting, against, apoptosis, and, inflammatory, damage, especially, during, 'hyperthermia,', 'hypoxia,', or, oxidative, stress])]). relacion([sujeto(['An', 'important,', yet, frequently, overlooked, function, of, some, 'HSPs', is, their, ability, to, function, as, extracellular, messengers, '(', also, termed, 'chaperokines)', that]), verbo([modulate]), complemento([immune, responses, within, the, 'CNS'])]). relacion([sujeto(['This', is, especially, so, since, several, studies, show, that, 'HSPs']), verbo([act]), complemento([therapeutically, by, modulating, innate, immune, activation, and, may, thus, serve, as, neuroprotective, agents])]). relacion([sujeto(['A', highly, 'regio-', and, diastereoselective, 'cross-coupling', of, 'allyl/propargyl', ethers, and, 'δ-ketoesters,']), verbo([mediated]), complemento([by, 'SmCp(R)2', 'reagents,', delivers, decorated, 'δ-lactones'])]). relacion([sujeto(['The', process]), verbo([has]), complemento([been, exploited, in, a, telescoped, approach, to, complex, cycloheptanols, in, which, two, 'Sm(ii)', reagents, act, in, turn, on, the, simple, starting, materials])]). relacion([sujeto(['Diabetes', 'mellitus-', '(', 'DM-)', related, vascular, diseases, attract]), verbo([increased]), complemento([attention, due, to, their, high, morbidity, and, mortality])]). relacion([sujeto(['Endothelial', microparticles, '(', 'EMPs)', are, new, diagnostic, and, therapeutic]), verbo([targets]), complemento([and, biomarkers, in, 'DM-related', vascular, disease])]). relacion([sujeto(['Circulating', 'EMPs', containing, biologically, active, substances]), verbo([act]), complemento([as, intercellular, signals, under, physiological, and, pathological, conditions])]). relacion([sujeto(['Recent', evidence]), verbo([suggests]), complemento([that, the, plasma, level, of, 'EMPs', is, significantly, higher, in, 'DM', patients, than, in, healthy, population, and, is, significantly, correlated, with, 'DM-related', complications])]). relacion([sujeto(['These', observations]), verbo([have]), complemento([prompted, speculation, that, 'EMPs', play, a, crucial, role, in, the, pathophysiology, of, 'DM'])]). relacion([sujeto(['As', any, 'chemical-based', drugs, could, not]), verbo([act]), complemento([against, the, tissue, cyst, stage, of, 'T'])]). relacion([sujeto(['The', present, study]), verbo([suggested]), complemento([that, both, 'TgENO2', and, 'TgTrxLp', were, potential, candidates, for, the, development, of, multicomponent, vaccines, against, toxoplasmosis])]). relacion([sujeto(['Oral', dichloroacetate, sodium, '(', 'DCA)']), verbo([has]), complemento([been, investigated, as, a, novel, metabolic, therapy, for, various, cancers, since, 2007, ',', based, on, data, from, 'Bonnet', et, al, that, 'DCA', can, trigger, apoptosis, of, human, 'lung,', breast, and, brain, cancer, cells])]). relacion([sujeto(['However,', 'Blackburn', et, al]), verbo([have]), complemento([demonstrated, that, 'DCA', can, also, act, as, a, cytostatic, agent, in, vitro, and, in, 'vivo,', without, causing, apoptosis, '(', programmed, cell, 'death)'])]). relacion([sujeto(['Since', the, natural, history, of, stage, 4, colon, cancer, consists, of, steady, progression]), verbo([leading]), complemento([to, disability, and, 'death,', this, case, highlights, a, novel, use, of, 'DCA', as, a, cytostatic, agent, with, a, potential, to, maintain, 'long-term', stability, of, 'advanced-stage', cancer])]). relacion([sujeto(['Growth', factors, such, as, bone, morphogenetic, proteins, 6, ',', 7, ',', 15, ',', and, two, isoforms, of, transforming, growth, 'factor-beta', '(', 'BMP6,', 'BMP7,', 'BMP15,', 'TGFB1,', and, 'TGFB2),', and, 'insulin-like', growth, factor, system]), verbo([act]), complemento([as, local, regulators, of, ovarian, follicular, development])]). relacion([sujeto(['To', elucidate, if, these, factors, as, well, as, others, candidate, 'genes,', such, as, estrogen, receptor, 1, '(', 'ESR1),', growth, differentiation, factor, 9, '(', 'GDF9),', 'follicle-stimulating', hormone, receptor, '(', 'FSHR),', luteinizing, hormone, receptor, '(', 'LHR),', bone, morphogenetic, protein, 'receptor,', type, 2, '(', 'BMPR2),', type, 1, 'insulin-like', growth, factor, receptor, '(', 'IGFR1),', and, key, steroidogenic, enzymes, cytochrome, 'P450', aromatase, and, 3, -, 'β-hydroxysteroid', dehydrogenase, '(', 'CYP19A1', and, 'HSD3B1)', could]), verbo([modulate]), complemento([or, influence, diestrus, on, the, onset, of, puberty, in, 'Brahman', 'heifers,', their, ovarian, mRNA, expression, was, measured, before, and, after, puberty, '(', luteal, 'phase)'])]). relacion([sujeto(['Differential', expression, of, ovarian, genes, could, be]), verbo([associated]), complemento([with, changes, in, follicular, dynamics, and, different, cell, populations, that, have, emerged, as, consequence, of, puberty, and, the, luteal, phase])]). relacion([sujeto(['The', emerging, hypothesis, is, that, 'BMP7', and, 'IGF1', are, 'co-expressed', and, may]), verbo([modulate]), complemento([the, expression, of, 'FSHR,', 'LHR', and, 'IGFR1,', and, 'CYP19A1'])]). relacion([sujeto(['BMP7', could, influence, the, downregulation, of, 'LHR', and, upregulation, of, 'FSHR', and, 'CYP19A1,', which]), verbo([mediates]), complemento([the, follicular, dynamics, in, heifer, ovaries])]). relacion([sujeto(['Upregulation', of, 'IGF1', expression, 'prepuberty,', compared, to, postpuberty, 'diestrus,', correlates, with]), verbo([increased]), complemento([levels, 'FSHR', and, 'CYP19A1'])]). relacion([sujeto(['The', heart]), verbo([provides]), complemento([the, body, with, oxygen, and, nutrients, and, assists, in, the, removal, of, metabolic, waste, through, the, blood, vessels, of, the, circulatory, system])]). relacion([sujeto(['Findings', obtained, from, mouse, models, and, human, diseases, with, 'FGF', signaling, disorders]), verbo([have]), complemento([indicated, that, several, 'FGFs', are, involved, in, heart, 'development,', 'health,', and, disease])]). relacion([sujeto(['Paracrine', 'FGFs', including, 'FGF8,', 'FGF9,', 'FGF10,', and, 'FGF16']), verbo([act]), complemento([as, paracrine, signals, in, embryonic, heart, development])]). relacion([sujeto(['In', heart, 'diseases,', serum, 'FGF15/19', levels, or, 'FGF21', and, 'FGF23', levels]), verbo([decrease]), complemento([or, 'increase,', 'respectively,', indicating, their, possible, roles, in, heart, pathophysiology])]). relacion([sujeto(['FGF2', and, 'FGF10', also]), verbo([stimulate]), complemento([the, cardiac, differentiation, of, cultured, stem, cells, and, cardiac, reprogramming, of, cultured, fibroblasts])]). relacion([sujeto(['These', findings]), verbo([provide]), complemento([new, insights, into, the, roles, of, 'FGF', signaling, in, the, heart, and, potential, therapeutic, strategies, for, cardiac, disorders])]). relacion([sujeto(['Information', on, drug, use, can, be, helpful, in]), verbo([preventing]), complemento(['high-risk', behavior, related, to, drug, abuse])]). relacion([sujeto(['The', first, usage, is, concomitant, with, the]), verbo([increased]), complemento([duration, of, 'sex,', an, increase, in, the, quality, and, quantity, of, sexual, 'pleasure,', a, delighted, 'orgasm,', and, feeling, more, control, of, the, sex, act])]). relacion([sujeto(['A']), verbo([decreased]), complemento([libido, and, various, sexual, dysfunctions, such, as, erectile, 'dysfunction,', premature, 'ejaculation,', and, losing, control, during, the, sex, act, will, appear, over, time])]). relacion([sujeto(['Oncofertility', is]), verbo([gained]), complemento([importance, because, of, increasing, cancer, 'incidence,', high, 'survivorship,', the, need, to, provide, a, good, quality, of, life, to, survivors, and, the, desire, of, patients, to, preserve, their, fertility])]). relacion([sujeto(['Gynaecologists', in, 'India']), verbo([act]), complemento([as, family, physicians, and, are, in, a, unique, position, to, guide, cancer, patients, on, issues, of, fertility, and, fertility, preservation])]). relacion([sujeto(['Studies']), verbo([have]), complemento([shown, that, over, 50, '%', of, 'end-of-life', discussions, take, place, for, the, first, time, in, the, hospital, and, that, terminally, ill, patients, often, have, unrealistic, views, regarding, the, possible, scope, of, treatment])]). relacion([sujeto(['A', 'multi-database', systematic, review, was, performed, on, published, studies, from, 2010, to, 'present,', and, there, were, none]), verbo([found]), complemento([measuring, the, effectiveness, of, the, 'PCIA'])]). relacion([sujeto(['Legislation', can]), verbo([have]), complemento([a, significant, effect, on, terminally, ill, 'patient\'s', access, to, palliative, care, services, and, can, change, the, culture, of, a, hospital, to, be, more, 'pro-palliative', for, the, appropriate, populations])]). relacion([sujeto(['The', 'intra-', and, 'inter-observer', reliability, was, excellent, in, 'AP', scapular, views, and, malpositions, in, 'extension/flexion', '(', 'ICC', '≥', 0.84, ')', but, tended, to]), verbo([decrease]), complemento([with, increasing, viewing, angle, in, 'retroversion/anteversion'])]). relacion([sujeto(['These', data]), verbo([suggest]), complemento([that, 3, 'D', reconstructions, are, more, reproducible, than, 'AP', scapular, radiographs, in, the, assessment, of, the, 'GPA', and, should, be, used, to, compare, data, in, different, 'studies,', to, predict, 'outcome,', define, 'malunion,', and, act, as, an, indication, for, surgery, in, patients, with, a, scapular, fracture])]). relacion([sujeto([miR156]), verbo([has]), complemento([been, shown, to, be, the, master, regulator, of, the, 'juvenile-to-adult', transition, in, plants])]). relacion([sujeto(['However,', the, mechanism, of, how, miR156, is, transcriptionally]), verbo([regulated]), complemento([still, remains, elusive])]). relacion([sujeto(['In', a, forward, genetic, 'screen,', we, identified, that, a, mutation, in, the, 'SWI2/SNF2', chromatin, remodeling, 'ATPase', 'BRAHMA', '(', 'BRM)', exhibited, an, accelerated, vegetative, phase, change, phenotype, by, reducing, the, expression, of, 'miR156,', which, in, turn]), verbo([caused]), complemento([a, corresponding, increase, in, the, levels, of, 'SQUAMOSA', 'PROMOTER', 'BINDING', 'PROTEIN', 'LIKE', genes])]). relacion([sujeto(['BRM']), verbo([regulates]), complemento([miR156, expression, by, directly, binding, to, the, 'MIR156A', promoter])]). relacion([sujeto(['Mutations', in, 'BRM', not, only]), verbo([increased]), complemento([occupancy, of, the, -, 2, and, +, 1, nucleosomes, proximal, to, the, transcription, start, site, at, the, 'MIR156A', locus, but, also, the, levels, of, trimethylated, histone, 'H3', at, 'Lys', 27])]). relacion([sujeto(['The', precocious, phenotype, of, brm, mutant, was, partially]), verbo([suppressed]), complemento([by, a, second, mutation, in, 'SWINGER', '(', 'SWN),', but, not, by, a, mutation, in, 'CURLEY', 'LEAF,', both, of, which, are, key, components, of, the, 'Polycomb', 'Group', 'Repressive', 'Complex', 2, in, plants])]). relacion([sujeto(['Our', results, indicate, that, 'BRM', and, 'SWN']), verbo([act]), complemento([antagonistically, at, the, nucleosome, level, to, 'fine-tune', the, temporal, expression, of, miR156, to, regulate, vegetative, phase, change, in, 'Arabidopsis'])]). relacion([sujeto(['Identifying', physical, links, among, proteins, and, between, drugs, and, their, protein]), verbo([targets]), complemento([is, essential, in, order, to, understand, the, mechanisms, through, which, both, proteins, themselves, and, the, molecules, they, are, targeted, with, act])]). relacion([sujeto(['Here', we, present, a, robust, and, sensitive, approach, to, screen, 'proteome-scale', collections, of, proteins, for]), verbo([binding]), complemento([to, proteins, or, small, molecules, using, the, well, validated, 'MAPPIT', '(', 'Mammalian', 'Protein-Protein', 'Interaction', 'Trap)', and, 'MASPIT', '(', 'Mammalian', 'Small', 'Molecule-Protein', 'Interaction', 'Trap)', assays])]). relacion([sujeto(['With', 'MAPPIT,', we, screened, a, 15, k, 'ORF', library, for]), verbo([binding]), complemento([partners, of, 'RNF41,', an, 'E3', ubiquitin, protein, ligase, implicated, in, receptor, 'sorting,', identifying, known, and, novel, interacting, proteins])]). relacion([sujeto(['The', potential, related, to, the, fact, that, 'MAPPIT', operates, in, living, human, cells, is, illustrated, in, a, screen, where, the, protein, collection, is, scanned, for, interactions, with, the, glucocorticoid, receptor, '(', 'GR)', in, its, unliganded, versus, 'dexamethasone-induced']), verbo([activated]), complemento([state])]). relacion([sujeto(['Several', proteins, were, identified, the, interaction, of, which, is]), verbo([modulated]), complemento([upon, ligand, binding, to, the, 'GR,', including, a, number, of, previously, reported, 'GR', interactors])]). relacion([sujeto(['Finally,', the, screening, technology, also, enables, detecting, small, molecule]), verbo([target]), complemento(['proteins,', which, in, many, drug, discovery, programs, represents, an, important, hurdle])]). relacion([sujeto(['We', show, the, efficiency, of, 'MASPIT-based']), verbo([target]), complemento([profiling, through, screening, with, 'tamoxifen,', a, 'first-line', breast, cancer, 'drug,', and, 'reversine,', an, investigational, drug, with, interesting, dedifferentiation, and, antitumor, activity])]). relacion([sujeto(['In', both, 'cases,', cell, microarray, screens, yielded, known, and, new, potential, drug]), verbo([targets]), complemento([highlighting, the, utility, of, the, technology, beyond, fundamental, biology])]). relacion([sujeto(['Part', 'D', enrollment, of, 'Medicare', beneficiaries, with, diabetes, gradually]), verbo([increased]), complemento([from, 45.7, '%', '(', 2006, ')', to, 52.4, '%', '(', 2011, ')'])]). relacion([sujeto(['Compared', with, years, 2000, -, 2005, ',', 'out-of-pocket', pharmacy, costs]), verbo([decreased]), complemento([by, 13.5, '%', '(', 'SE', 2.1, ')', for, all, 'Medicare', beneficiaries, with, diabetes, following, 'Part', 'D', 'implementation;', on, 'average,', 'Part', 'D', beneficiaries, had, 5.3, '%', '(', 0.8, ')', lower, costs, compared, with, those, without, 'Part', 'D'])]). relacion([sujeto(['Compared', with, a, younger, group, with, 'diabetes,', 'out-of-pocket', pharmacy, costs]), verbo([decreased]), complemento([by, 19.4, '%', '(', 1.7, ')', for, 'Medicare', beneficiaries, after, 'Part', 'D'])]). relacion([sujeto(['Part', 'D', beneficiaries, with, diabetes, who, experienced, the, coverage, gap]), verbo([decreased]), complemento([from, 60.1, '%', '(', 2006, ')', to, 40.9, '%', '(', 2011, ')', over, this, period])]). relacion([sujeto(['These', findings, demonstrate, that, although, 'Medicare', 'Part', 'D']), verbo([has]), complemento([been, effective, in, reducing, the, 'out-of-pocket', cost, burden, of, prescription, 'drugs,', approximately, two, out, of, five, 'Part', 'D', beneficiaries, with, diabetes, experienced, the, coverage, gap, in, 2011])]). relacion([sujeto(['Together,', these, effects, reduced, mMDSC, accumulation, in, 'tumor-bearing', 'hosts,', limiting, the, outgrowth, of, 'KRas-driven', breast, 'tumors,', even, though, trametinib, largely, failed, to, directly]), verbo([inhibit]), complemento([tumor, cell, proliferation])]). relacion([sujeto(['Accordingly,', trametinib, impeded, tumor, progression, in, vivo, through, a, mechanism]), verbo([requiring]), complemento(['CD8(+)', 'T', 'cells,', which, was, paradoxical, given, the, 'drug\'s', reported, ability, to, inhibit, effector, lymphocytes])]). relacion([sujeto(['More', 'broadly,', by]), verbo([providing]), complemento([a, more, incisive, view, into, how, 'MEK', inhibitors, may, act, against, 'tumors,', our, findings, expand, their, potential, uses, to, generally, block, mMDSC, 'expansion,', which, occurs, widely, in, cancers, to, drive, their, growth, and, progression])]). relacion([sujeto(['The', aim, of, this, qualitative, 'meta-synthesis', was, to, search, and, then, synthesise, family, 'caregivers\'', experiences, of]), verbo([providing]), complemento([care, to, individuals, with, 'Parkinson\'s', disease, '(', 'PD)'])]). relacion([sujeto(['Noblit', and, 'Hare\'s', 'seven-stage', approach, was, used, to]), verbo([provide]), complemento([a, 'higher-order', interpretation, of, how, family, 'caregivers\'', experienced, the, effects, of, taking, on, a, caregiving, role])]). relacion([sujeto(['The', process, of, reciprocal, translation, resulted, in, four, overarching, 'themes:', '(', 1, ')', the, need, to, carry, on, as, usual, -, '\'', the, caregiver, must, continue, with, his, 'life\';', '(', 2, ')', the, importance, of, support, in, facilitating, coping, -, '\'', 'I\'m', still, going, back, to, the, support, 'group\';', '(', 3, ')', the, difficult, balancing]), verbo([act]), complemento([between, caregiving, and, caregiver, needs, -, '\'', 'I', cannot, get, sick, because, 'I\'m', a, 'caregiver\';', '(', 4, ')', conflicts, in, seeking, information, and, knowledge, -, '\'', maybe, better, not, to, 'know\''])]). relacion([sujeto(['Hybrid', 'Arabidopsis', plants, undergo, epigenetic, reprogramming, producing]), verbo([decreased]), complemento([levels, of, 24, -, nt, siRNAs, and, altered, patterns, of, 'DNA', methylation, that, can, affect, gene, expression])]). relacion([sujeto(['We', show, that, 'Pol', 'IV-dependent', sRNAs, are]), verbo([required]), complemento([to, establish, 'TCM', events])]). relacion([sujeto(['The', changes, in, 'DNA', methylation, and, the]), verbo([associated]), complemento([changes, in, sRNA, levels, in, the, 'F1', hybrid, can, be, maintained, in, subsequent, generations, and, affect, hundreds, of, regions, in, the, 'F2', epigenome])]). relacion([sujeto(['The', change, in, methylation, at, these, regions, is]), verbo([associated]), complemento([with, the, presence, of, sRNAs])]). relacion([sujeto(['Loci', without, any, sRNA, activity, can]), verbo([have]), complemento([altered, methylation, 'states,', suggesting, that, a, 'sRNA-independent', mechanism, may, also, contribute, to, the, altered, methylation, state, of, the, 'F1', and, 'F2', generations])]). relacion([sujeto(['Here', we, use, a, 'refactored,']), verbo([modular]), complemento([in, vivo, system, containing, the, micrococcin, 'P1', '(', 'MP1)', biosynthetic, genes, '(', 'TclIJKLMNPS)', from, 'Macrococcus', caseolyticus, str, 115, in, a, genetically, tractable, 'Bacillus', subtilis, strain, to, parse, the, processing, steps, of, this, pathway])]). relacion([sujeto(['We']), verbo([found]), complemento([that, two, major, phases, of, molecular, maturation, are, separated, by, a, key, 'C-terminal', processing, step])]). relacion([sujeto(['This', 'TclP-mediated', oxidative, decarboxylation, is, a]), verbo([required]), complemento([step, for, the, peptide, to, progress, to, phase, 'II'])]). relacion([sujeto(['A', 'C-terminal', 'reductase,', 'TclS,', can, optionally]), verbo([act]), complemento([on, the, substrate, 'peptide,', yielding, 'MP1,', and, is, shown, to, act, late, in, the, pathway])]). relacion([sujeto(['To', circumvent, this, 'issue,', the, 'Pt2ML/Os/Pd3Al', catalyst]), verbo([has]), complemento([been, designed, to, suppress, the, migration, of, 'Al', by, inserting, an, 'Os', monolayer, at, the, interface, between, the, 'Pd3Al', core, and, two, 'Pt', monolayers])]). relacion([sujeto(['As', an, 'ORR', 'electrocatalyst,', the, relatively, weak, adsorption, ability, of, 'Pt2ML/Os/Pd3Al']), verbo([suggests]), complemento([improved, 'ORR', activity])]). relacion([sujeto(['Finally,', a, representative, 'OOH', association, mechanism, with, low, reaction, barriers, of, 0.46, ',', 0.31, ',', 0.38, and, 0.41, eV, for, the, 'OOH', 'formation,', 'OOH', 'dissociation,', 'OH', formation, and, 'H2O', formation, steps]), verbo([suggests]), complemento([that, the, catalyst, can, effectively, activate, the, 'O-O', bond, and, eliminate, 'OH,', which, can, act, as, a, catalytic, poison])]). relacion([sujeto(['These', findings]), verbo([suggest]), complemento([the, design, of, stable, sandwich, catalysts, as, potential, candidates, for, 'ORR', electrocatalysis])]). relacion([sujeto(['A', high, number, density, of, oxide, nanoclusters, dispersed, throughout, a, 'BCC', 'Fe', matrix]), verbo([act]), complemento([as, trapping, sites, for, helium, and, prevent, its, eventual, delivery, to, high, risk, nucleation, sites])]). relacion([sujeto(['Investigation', of, the, electronic, structure, and, a, mapping, of, the, potential, energy, landscape]), verbo([reveals]), complemento([that, the, localized, 'iono-covalent', bonds, present, within, the, oxides, create, a, potential, 'energy-well', within, the, metallically, bonded, 'BCC', 'Fe', 'matrix,', so, that, trapping, of, helium, at, the, oxide, nanocluster, is, thermodynamically, and, kinetically, favorable])]). relacion([sujeto(['We', demonstrate, that, oxygen, vacancies, '(', 'VO)', and, titanium, interstitials, '(', 'Tii)']), verbo([act]), complemento([as, shallow, 'donors,', and, can, form, at, substantial, 'concentrations,', giving, rise, to, free, electrons, with, carrier, densities, from, 10, '(', 11, ')', to, 10, '(', 19, ')', 'cm(-3)', under, 'oxygen-rich', and, 'oxygen-poor', 'conditions,', respectively])]). relacion([sujeto(['The', titanium, vacancies, '(', 'VTi),', identified, as, deep, acceptors, and]), verbo([induced]), complemento([hole, 'carriers,', are, incapable, of, fully, compensating, for, the, free, electrons, originating, from, the, 'donor-type', defects, at, any, oxygen, chemical, potential])]). relacion([sujeto(['At', a, typical, annealing, temperature, and, under, a, typical, oxygen, partial, 'pressure,', the, carrier, concentration, is]), verbo([found]), complemento([to, be, approximately, 5, ×, 10, '(', 13, ')', 'cm(-3)'])]). relacion([sujeto(['Our']), verbo([binding]), complemento([and, crystal, structure, analyses, show, that, 'MFAP1', and, 'Snu23', contact, 'Prp38', via, 'ER/K', 'motif-stabilized', single, α, 'helices,', which, have, previously, been, recognized, only, as, 'rigid connectors', or, force, springs, between, protein, domains])]). relacion([sujeto(['A', variant, of, the, 'Prp38-binding', single, α, helix, of, 'MFAP1,', in, which, 'ER/K', motifs, not]), verbo([involved]), complemento([in, 'Prp38', binding, were, 'mutated,', was, less, 'α-helical', in, isolation, and, showed, a, reduced, 'Prp38', 'affinity,', with, opposing, tendencies, in, interaction, enthalpy, and, entropy])]). relacion([sujeto(['MFAP1,', 'Snu23,', and, several, other, spliceosomal, proteins, contain, multiple, regions, that, likely, form, single, α, helices, via, which, they, might, tether, several]), verbo([binding]), complemento([partners, and, act, as, intermittent, scaffolds, that, facilitate, remodeling, steps, during, assembly, of, an, active, spliceosome])]). relacion([sujeto(['The', desolvation, of, ionizable, residues, in, the, active, sites, of, enzymes, and, the, subsequent, effects, on, catalysis, and, thermostability]), verbo([have]), complemento([been, studied, in, model, 'systems,', yet, little, about, how, enzymes, can, naturally, evolve, to, include, active, sites, with, highly, reactive, and, desolvated, charges, is, known])]). relacion([sujeto(['Variants', of, triazine, hydrolase, '(', 'TrzN)', with, significant, differences, in, their, active, sites]), verbo([have]), complemento([been, isolated, from, different, bacterial, 'strains:', 'TrzN', from, 'Nocardioides', sp])]). relacion([sujeto([strain, 'AN3']), verbo([has]), complemento([a, noncatalytic, glutamine, residue, '(', 'Gln241)', at, an, equivalent, 'position,', surrounded, by, hydrophilic, residues, '(', 'Thr214', and, 'His215)'])]). relacion([sujeto(['To', understand, how, and, why, these, variants]), verbo([have]), complemento(['evolved,', a, series, of, 'TrzN', mutants, were, generated, and, characterized])]). relacion([sujeto(['These', results, show, that, desolvation, by, 'second-shell', residues]), verbo([increases]), complemento([the, pKa, of, 'Glu241,', allowing, it, to, act, as, a, general, acid, at, neutral, pH])]). relacion([sujeto(['However,', significant, thermostability, 'trade-offs', are]), verbo([required]), complemento([to, incorporate, the, ionizable, 'Glu241', in, the, active, site, and, to, then, enclose, it, in, a, hydrophobic, microenvironment])]). relacion([sujeto(['Analysis', of, 'high-resolution', crystal, structures, shows, that, there, are, almost, no, structural, changes, to, the, overall, configuration, of, the, active, site, due, to, these, 'mutations,']), verbo([suggesting]), complemento([that, the, changes, in, activity, and, thermostability, are, purely, based, on, the, altered, electrostatics])]). relacion([sujeto(['The', natural, evolution, of, these, enzyme, isoforms]), verbo([provides]), complemento([a, unique, system, in, which, to, study, the, fundamental, process, of, charged, residue, desolvation, in, enzyme, catalysis, and, its, relative, contribution, to, the, creation, and, evolution, of, an, enzyme, active, site])]). relacion([sujeto(['Here,', we, show, that, 'TP53', 'exon-6', truncating, mutations, occur, at, higher, than, expected, frequencies, and, produce, proteins, that, lack, canonical, p53, tumor, suppressor, activities, but]), verbo([promote]), complemento([cancer, cell, 'proliferation,', 'survival,', and, metastasis])]). relacion([sujeto(['Accordingly,', these, mutants, can, localize, to, the, mitochondria, where, they]), verbo([promote]), complemento([tumor, phenotypes, by, binding, and, activating, the, mitochondria, inner, pore, permeability, 'regulator,', 'Cyclophilin', 'D', '(', 'CypD)'])]). relacion([sujeto(['Together,', our, studies]), verbo([reveal]), complemento([that, 'TP53', 'exon-6', truncating, 'mutations,', contrary, to, current, 'beliefs,', act, beyond, p53, loss, to, promote, 'tumorigenesis,', and, could, inform, the, development, of, strategies, to, target, cancers, driven, by, these, prevalent, mutations])]). relacion([sujeto(['The', process, model, proposes, that, the, ego, depletion, effect, is, due, to, '(', 'a)', an]), verbo([increase]), complemento([in, motivation, toward, 'indulgence,', and, '(', 'b)', a, decrease, in, motivation, to, control, behaviour, following, an, initial, act, of, 'self-control'])]). relacion([sujeto(['Motivation', was, more, strongly, predictive, of, intake, for, those, in, the, 'non-depletion', 'condition,']), verbo([providing]), complemento([partial, support, for, the, 'reflective-impulsive', model])]). relacion([sujeto(['Ego', depletion, did, not, affect, 'desire,', nor, did, depletion, moderate, the, effect, of, desire, on, 'intake,', indicating, that, desire, may, be, an, appropriate]), verbo([target]), complemento([for, reducing, unhealthy, behaviour, across, situations, where, 'self-control', resources, vary])]). relacion([sujeto(['Electrochemically', splitting, water, for, hydrogen, evolution]), verbo([has]), complemento([attracted, a, lot, attention, and, developed, into, a, promising, approach, to, produce, hydrogen, energy])]). relacion([sujeto(['In', this, 'paper,', we]), verbo([reported]), complemento([a, concise, and, effective, strategy, to, fabricate, the, novel, 'MoWS2', composite, for, use, as, the, electrocatalyst, through, a, hydrothermal, method, for, the, first, time])]). relacion([sujeto(['The', final, obtained, 'MoWS2', composite, demonstrated, a, 'well-defined', hierarchical, structure, and, established, that, its, densely, stacked, nanopetals]), verbo([act]), complemento([as, the, active, sites, in, the, corresponding, hydrogen, evolution, reaction, '(', 'HER)', processes])]). relacion([sujeto(['Experimental', results, show, that, the, composites, can, deliver, a, clearly]), verbo([promoted]), complemento(['HER', activity, and, are, superior, to, the, pure, structure])]). relacion([sujeto(['The', charge, distribution, of, 'MoWS2', composite, indicates, that, electrons, can, directionally, transfer, from, 'WS2', to, the, neighboring, 'MoS2', and, form, an, &, 'quot;electron-rich"', 'configuration,', which, is, beneficial, to]), verbo([increase]), complemento([the, 'HER', rate, and, promote, the, overall, performance])]). relacion([sujeto(['This', thorough, research, will, not, only]), verbo([provide]), complemento([new, thought, to, the, analyses, and, elucidation, of, the, inner, mechanism, of, the, 'HER', process, for, this, kind, of, 'two-dimensional', composite, but, also, guide, further, work, on, the, basis, of, experimental, and, calculation, results])]). relacion([sujeto(['During', the, last, 'decade,', neoadjuvant, chemotherapy, '(', 'NACT)', of, early, breast, cancer, '(', 'EBC)', evolved, from, a, therapy, intended, to, enable, operability, to, a, standard, treatment, option, aiming, for]), verbo([increasing]), complemento([cure, rates, equivalent, to, adjuvant, chemotherapy, '(', 'ACT)'])]). relacion([sujeto(['In', 'parallel,', improvements, in, the, quality, control, of, breast, cancer, care]), verbo([have]), complemento([been, established, in, specialized, breast, care, units])]). relacion([sujeto(['In', 'addition,', frequency, of, pathologic, complete, response, '(', 'pCR)', defined, as, no, tumor, residues, in, breast, and, axilla, '(', ypT0, 'ypN0)', at, surgery, following, 'NACT']), verbo([increased]), complemento([from, 12, &, 'nbsp;%', in, 2003, to, 35, &, 'nbsp;%', in, 2014])]). relacion([sujeto(['The', greatest, effect, was, observed, in, 'HER2+ breast', cancer, with, an]), verbo([increase]), complemento([in, patients, achieving, pCR, from, 24, to, 68, &, 'nbsp;%'])]). relacion([sujeto(['The']), verbo([increase]), complemento([in, pCR, rate, over, time, suggests, improvement, in, outcome, accomplished, by, a, multidisciplinary, 'decision-making', process, and, stringent, measures, for, quality, control])]). relacion([sujeto(['The', major, covalent, adduct, formed, between, a, '(', 13, ')', 'C-labelled', formaldehyde]), verbo([activated]), complemento(['bis-amino', mitoxantrone, analogue, '(', 'WEHI-150)', and, the, hexanucleotide, 'd(CG(5Me)CGCG)2', has, been, isolated, by, 'HPLC', chromatography, and, the, structure, determined, by, 'NMR', spectroscopy])]). relacion([sujeto(['This', paper]), verbo([reports]), complemento([development, and, testing, of, a, novel, 'cross-flow', wet, electrostatic, precipitator, '(', 'WESP),', recently, patented, at, 'Ohio', 'University,', that, utilizes, vertical, columns, of, permeable, material, in, the, form, of, polypropylene, ropes, placed, in, a, 'cross-flow', configuration, within, a, flue, gas, stream])]). relacion([sujeto(['The', 'cross-flow', design]), verbo([has]), complemento([large, surface, 'area,', which, provides, scrubbing, 'action;', 'therefore,', it, has, the, potential, for, removing, multiple, 'pollutants,', including, 'particulates,', 'gases,', 'vapors,', and, mists])]). relacion([sujeto(['In', this, new, 'method,', the, ropes, are, kept, wet, by, the, liquid, '(', 'water)', introduced, from, the, top, of, the, cells, running, downward, on, the, ropes, by, capillary, 'action,', making, the, permeable, materials]), verbo([act]), complemento([as, the, ground, electrode, for, capturing, particles, from, the, flue, gas])]). relacion([sujeto(['Preliminary', testing]), verbo([has]), complemento([shown, an, efficiency, of, well, above, 80, '%', using, two, cells, and, three, sets, of, discharge, electrodes])]). relacion([sujeto(['The', electric, field, strength]), verbo([has]), complemento([a, substantial, effect, on, the, collection, efficiency])]). relacion([sujeto(['Also,', the, pressure, drop, test, results, indicate, that, there, is, a, potential, to]), verbo([increase]), complemento([the, collection, 'area,', 'which,', in, 'turn,', will, increase, the, collection, efficiency, further])]). relacion([sujeto(['A', method, to, image, taurine, distributions, within, the, central, nervous, system, and, other, organs]), verbo([has]), complemento([long, been, sought])]). relacion([sujeto(['Combining', numerous, indirect, 'measurements,', taurine, is, known, to, play, critical, roles, in, brain, function, during, health, and, disease, and, is, proposed, to]), verbo([act]), complemento([as, a, 'neuro-osmolyte,', 'neuro-modulator,', and, possibly, a, 'neuro-transmitter'])]). relacion([sujeto(['Elucidation', of, 'taurine\'s', neurochemical, roles, and, importance, would, be, substantially]), verbo([enhanced]), complemento([by, a, direct, method, to, visualize, 'alterations,', due, to, physiological, and, pathological, events, in, the, 'brain,', in, the, local, concentration, of, taurine, at, or, near, cellular, spatial, resolution, in, vivo, or, in, situ, in, tissue, sections])]). relacion([sujeto(['We', thus]), verbo([have]), complemento([developed, chemically, specific, 'X-ray', fluorescence, imaging, '(', 'XFI)', at, the, sulfur, 'K-edge', to, image, the, sulfonate, group, in, taurine, in, situ, in, ex, vivo, tissue, sections])]). relacion([sujeto(['We']), verbo([report]), complemento([quantitative, technique, validation, by, imaging, taurine, in, the, cerebellum, and, hippocampus, regions, of, the, rat, brain])]). relacion([sujeto(['Further,', we, apply, the, technique, to, image, taurine]), verbo([loss]), complemento([from, the, vulnerable, 'CA1', '(', cornus, ammonis, 1, ')', sector, of, the, rat, hippocampus, following, global, brain, ischemia])]). relacion([sujeto(['The', 'location-specific']), verbo([loss]), complemento([of, taurine, from, 'CA1', but, not, 'CA3', neurons, following, ischemia, reveals, osmotic, stress, may, be, a, key, factor, in, delayed, neurodegeneration, after, a, cerebral, ischemic, insult, and, highlights, the, significant, potential, of, chemically, specific, 'XFI', to, study, the, role, of, taurine, in, brain, disease])]). relacion([sujeto(['Gold', nanoparticles, '(', 'GNP)']), verbo([act]), complemento([as, a, radiosensitizer, in, radiation, therapy])]). relacion([sujeto(['However,', recent, studies]), verbo([have]), complemento([shown, contradictory, evidence, in, terms, of, radiosensitization, in, the, presence, of, 'GNP', combined, with, 'X-ray', megavoltage, energy, '(', 'MV)', on, different, cell, types])]). relacion([sujeto(['In', 'contrast,', 'GNP,', in, combination, with, radiation, '(', 9, 'MV),']), verbo([induced]), complemento([more, apoptosis])]). relacion([sujeto(['It', was, concluded, that, 'GNP', may, work, as, 'bio-inert', material, on, 'HT-29', cancer, cells, and, their, enhancement, of, radiosensitization, may, be, due, to]), verbo([increase]), complemento([in, the, absorbed, irradiation, dose])]). relacion([sujeto(['Analyses', of, circulating, immune, cells, by, flow, cytometry]), verbo([have]), complemento([revealed, 'MS-associated', alterations, in, the, composition, and, function, of, 'T', and, 'B', cell, 'subsets,', including, temporal, changes, associated, with, disease, activity])]). relacion([sujeto(['Utilizing', the, analytical, power, of, modern, flow, 'cytometers,', researchers, are, now, well, positioned, to, monitor, immunological, changes]), verbo([associated]), complemento([with, disease, activity, or, 'intervention,', describe, immunological, signatures, with, predictive, value, and, identify, targets, for, therapeutic, drug, development])]). relacion([sujeto(['This', review, discusses, the, contribution, of, various, 'T', and, 'B', lymphocyte, subsets, to, 'MS', 'pathogenesis,']), verbo([provides]), complemento([current, and, relevant, phenotypical, descriptions, to, assist, in, experimental, design, and, highlights, areas, of, future, research])]). relacion([sujeto(['Although', 2, a, and, 2, b, were]), verbo([reported]), complemento([previously, in, the, 'literature,', 11, compounds, were, synthesized, '(', nine, of, them, were, newly, 'synthesized)', and, the, tyrosinase, inhibitory, effects, and, antioxidant, activities, of, these, compounds, were, studied, for, the, first, time])]). relacion([sujeto(['Kinetic', studies, revealed, it, to]), verbo([act]), complemento([as, 'non-competitive', tyrosinase, inhibitor, with, a, 'Ki', value, of, 50.2, µM])]). relacion([sujeto(['All', of, these, results, indicated, that, the, compounds, might]), verbo([have]), complemento([potential, application, as, tyrosinase, inhibitors])]). relacion([sujeto(['Rnd', proteins, are, atypical, members, of, the, 'Rho', 'GTPase', family, that]), verbo([induce]), complemento([actin, cytoskeletal, reorganization, and, cell, rounding])]). relacion([sujeto(['Rnd', proteins]), verbo([have]), complemento([been, reported, to, bind, to, the, intracellular, domain, of, several, plexin, 'receptors,', but, whether, plexins, contribute, to, the, 'Rnd-induced', rounding, response, is, not, known])]). relacion([sujeto(['Here', we, show, that, 'Rnd3']), verbo([interacts]), complemento([preferentially, with, 'plexin-B2', of, the, three, 'plexin-B', 'proteins,', whereas, 'Rnd2', interacts, with, all, three, 'B-type', 'plexins,', and, 'Rnd1', shows, only, very, weak, interaction, with, 'plexin-B', proteins, in, immunoprecipitations])]). relacion([sujeto(['Plexin-B1']), verbo([has]), complemento([been, reported, to, act, as, a, 'GAP', for, 'R-Ras', 'and/or', 'Rap1', proteins])]). relacion([sujeto(['We', show, that, all, three, 'plexin-B', proteins]), verbo([interact]), complemento([with, 'R-Ras', and, 'Rap1,', but, 'Rnd', proteins, do, not, alter, this, interaction, or, 'R-Ras', or, 'Rap1', activity])]). relacion([sujeto(['We', demonstrate, that, 'plexin-B2']), verbo([promotes]), complemento(['Rnd3-induced', cell, rounding, and, loss, of, stress, 'fibres,', and, enhances, the, inhibition, of, 'HeLa', cell, invasion, by, 'Rnd3'])]). relacion([sujeto(['We', identify, the, amino, acids, in, 'Rnd3', that, are]), verbo([required]), complemento([for, 'plexin-B2', 'interaction,', and, show, that, mutation, of, these, amino, acids, prevents, 'Rnd3-induced', morphological, changes])]). relacion([sujeto(['These', results, indicate, that, 'plexin-B2', is, a, downstream]), verbo([target]), complemento([for, 'Rnd3,', which, contributes, to, its, cellular, function])]). relacion([sujeto(['Human', lung, fibroblasts, '(', 'HLFs)']), verbo([act]), complemento([as, innate, immune, sentinel, cells, that, amplify, the, inflammatory, response, to, injurious, stimuli])]). relacion([sujeto(['Here,', we, use]), verbo([targeted]), complemento([lipidomics, to, explore, the, hypothesis, that, 'HLFs', also, play, an, active, role, in, the, resolution, of, inflammation])]). relacion([sujeto(['Next,', we, used, a, 'cell-based', luciferase, reporter, to, confirm, the, ability, of, 'HLF', supernatants, to]), verbo([activate]), complemento(['PPARγ,', 'demonstrating,', for, the, first, 'time,', that, primary, 'HLFs', activated, with, proinflammatory, 'IL-1β', or, cigarette, smoke, extract, produce, functional, 'PPARγ', 'ligands;', this, phenomenon, is, temporally, 'regulated,', 'COX-2-', and, 'lipocalin-type', 'PGD', 'synthase-dependent,', and, enhanced, by, arachidonic, acid, supplementation])]). relacion([sujeto(['Finally,', we, used, luciferase, reporter, assays, to, show, that, several, of, the, 'PGs', in, the, lipidome, of]), verbo([activated]), complemento(['HLFs', independently, activate, 'PPARγ', 'and/or', inhibit, 'NFκB'])]). relacion([sujeto(['These', results, indicate, that, 'HLFs,', as, immune, 'sentinels,']), verbo([regulate]), complemento([both, proinflammatory, and, proresolving, responses, to, injurious, stimuli])]). relacion([sujeto(['This', novel, endogenous, resolution, pathway, represents, a, new, therapeutic]), verbo([target]), complemento([for, globally, important, inflammatory, diseases, such, as, chronic, obstructive, pulmonary, disease])]). relacion([sujeto(['The', purpose, of, this, review, is, to, summarize, current, studies, detailing, the, impact, of, unilateral, sensorineural, hearing]), verbo([loss]), complemento([in, children, and, the, most, current, modalities, of, treatment, used, in, its, management])]). relacion([sujeto(['Current', studies, corroborate, historic, views, on, the, impact, of, unilateral, sensorineural, hearing]), verbo([loss]), complemento([on, patient, wellbeing, and, academic, success, and, stress, the, use, of, additional, surveillance, and, studies, to, diagnose, those, patients, that, may, pass, standard, screening, practices, and, suffer, from, lack, of, prompt, and, proper, care])]). relacion([sujeto(['With', respect, to, 'management,', notable, findings, include, the, continuous, development, of, improved, conventional, and, contralateral, routing, of, signal, amplification, devices, that, may]), verbo([act]), complemento([to, provide, alternatives, to, percutaneous, 'bone-anchored', hearing, aid, implantation])]). relacion([sujeto(['Due', to, dissatisfaction, with, sound, 'localization,', a, new, and, significant, development, is, the, burgeoning, accumulation, of, research, on, cochlear, implantation, for, the, treatment, of, unilateral, sensorineural, hearing]), verbo([loss]), complemento([in, children])]). relacion([sujeto(['With', advances, in, technology, in, historic, modalities, of, 'treatment,', and, the, advent, of, new, modalities, such, as, cochlear, 'implantation,', the, clinician]), verbo([has]), complemento([a, wide, armamentarium, by, which, to, provide, treatment, to, patients, based, on, clinical, circumstances, and, patient, desires])]). relacion([sujeto(['The', 'FDA']), verbo([has]), complemento([published, several, guidance, documents, to, facilitate, implementation, of, the, 'BPCI', 'Act'])]). relacion([sujeto(['Utilizing', coronary, artery, 'ligation-induced', murine, 'MI', 'models,', we]), verbo([found]), complemento([that, myocardial, 'BCAA', catabolism, was, significantly, impaired, in, response, to, permanent, 'MI,', therefore, leading, to, an, obvious, elevation, of, myocardial, 'BCAA', abundance])]). relacion([sujeto(['In', 'MI-operated', 'mice,', oral, 'BCAA', administration, further]), verbo([increased]), complemento([cardiac, 'BCAA', 'levels,', activated, the, mammalian, target, of, rapamycin, '(', 'mTOR)', 'signaling,', and, exacerbated, cardiac, dysfunction, and, remodeling])]). relacion([sujeto(['These', data, demonstrate, that, 'BCAAs']), verbo([act]), complemento([as, a, direct, contributor, to, 'post-MI', cardiac, pathologies])]). relacion([sujeto(['Furthermore,', these, 'BCAA-mediated', deleterious, effects, were, improved, by, rapamycin, 'cotreatment,']), verbo([revealed]), complemento([an, indispensable, role, of, mTOR, in, 'BCAA-mediated', adverse, effects, on, cardiac, 'function/structure', 'post-MI'])]). relacion([sujeto(['In', 'conclusion,', our, data]), verbo([provide]), complemento([the, evidence, that, impaired, cardiac, 'BCAA', catabolism, directly, contributes, to, 'post-MI', cardiac, dysfunction, and, remodeling])]). relacion([sujeto(['Bile', acids, are, synthesized, from, cholesterol, and, are, known, to, be]), verbo([involved]), complemento([with, the, emulsification, and, digestion, of, dietary, lipids, and, 'fat-soluble', vitamins])]). relacion([sujeto(['Outside', of, this, 'role,', bile, acids, can]), verbo([act]), complemento([as, cell, signaling, effectors, through, binding, and, activating, receptors, on, both, the, cell, membrane, and, nucleus])]). relacion([sujeto(['Numerous']), verbo([reports]), complemento([have, investigated, these, signaling, pathways, in, conditions, where, the, liver, is, damaged])]). relacion([sujeto(['More', 'recently,', effort]), verbo([has]), complemento([been, made, to, investigate, the, role, of, bile, acids, in, diseases, outside, of, those, associated, with, liver, damage])]). relacion([sujeto(['No', current, studies]), verbo([have]), complemento([adequately, examined, mental, health, professional, experiences, of, working, with, 'Flexible', 'ACT'])]). relacion([sujeto(['The', analysis, resulted, in, the, core, 'category:', &, 'quot;Flexible', 'ACT', and, the, shared, caseload, create, a, common, action, 'space"', and, three, main, 'categories:', '(', 1, ')', &, 'quot;Flexible', 'ACT', fills, the, need, for, a, systematic, approach, to, crisis, 'intervention";', '(', 2, ')', &, 'quot;Flexible', 'ACT']), verbo([has]), complemento([advantages, in, the, psychosocial, working, 'environment";', and, '(', 3, ')', &, 'quot;Flexible', 'ACT', increases, the, quality, of, 'care"'])]). relacion([sujeto(['Mental', health, professionals, may, benefit, from, working, with, the, 'Flexible', 'ACT', model, through]), verbo([decreased]), complemento(['job-strain', and, 'stress,', increased, feeling, of, being, in, control, over, their, work, 'situation,', and, experiences, of, providing, higher, quality, of, care])]). relacion([sujeto(['Attention', bias, modification, treatment, '(', 'ABMT)']), verbo([targets]), complemento(['threat-related', attention, biases, in, anxiety, disorders])]). relacion([sujeto(['Most', clinical, trials, of, 'ABMT']), verbo([have]), complemento([focused, on, adults, or, small, samples, of, youth])]). relacion([sujeto(['Both', 'ABMT', and, 'ACT']), verbo([induced]), complemento([significant, reductions, in, clinician, and, 'self-rated', social, anxiety, '(', 'ps < '])]). relacion([sujeto(['Despite', significant, reductions, in, social, 'anxiety,', no, specific, evidence, for, 'ABMT', was]), verbo([found]), complemento([relative, to, a, control, condition])]). relacion([sujeto(['Cannabinoids', apparently]), verbo([act]), complemento([on, inflammation, through, mechanisms, different, from, those, of, agents, such, as, nonsteroidal, 'anti-inflammatory', drugs, '(', 'NSAIDs)'])]). relacion([sujeto(['As', a, 'class,', the, cannabinoids, are, generally, free, from, the, adverse, effects]), verbo([associated]), complemento([with, 'NSAIDs'])]). relacion([sujeto(['Their', clinical, development, thus]), verbo([provides]), complemento([a, new, approach, to, treatment, of, diseases, characterized, by, acute, and, chronic, inflammation, and, fibrosis])]). relacion([sujeto([',', 'North', 'Chicago,', 'IL,', 'USA),', and, 'Sativex', '(', 'Cannabis', 'extract;', 'GW', 'Pharmaceuticals,', 'Cambridge', 'United', 'Kingdom)-that']), verbo([have]), complemento(['anti-inflammatory', effects])]). relacion([sujeto(['Changes', of, 'Hb', expression, under, 'hypoxia,', together, with, the, investigations, of, spleen, somatic, 'index,', kidney, somatic, index, and, 'Hb', concentration, in, 'circulation,']), verbo([suggest]), complemento([that, the, kidney, may, not, only, serve, as, the, erythropoietic, 'organ,', but, also, act, as, the, major, blood, reservoir, in, 'S'])]). relacion([sujeto(['Successful', examples, for, precise, tumor]), verbo([targeting]), complemento([are, diagnostic, and, therapeutic, radioligands])]). relacion([sujeto(['However,', patients, with, tumors]), verbo([expressing]), complemento([low, levels, of, the, relevant, molecular, targets, are, deemed, ineligible, for, such, targeted, approaches])]). relacion([sujeto(['We', identified, 9, drugs, that]), verbo([act]), complemento([as, epigenetic, 'modifiers,', including, the, inhibitor, of, 'DNA', methyltransferase, decitabine, as, well, as, the, inhibitors, of, histone, deacetylase, tacedinaline, and, romidepsin])]). relacion([sujeto(['We', present, an, approach, that, uses, epigenetic, modifiers, to, improve, sstr2]), verbo([targeting]), complemento([in, vitro, and, in, vivo])]). relacion([sujeto(['Translation', of, this, method, into, the, clinic, may, potentially, convert, patients, ineligible, for]), verbo([targeted]), complemento([imaging, and, therapy, to, eligible, candidates])]). relacion([sujeto(['Primary', and, secondary, school, ages]), verbo([have]), complemento([been, considered, key, moments, to, address, the, decrease, of, 'moderate-tovigorous', physical, activity, '(', 'MVPA)'])]). relacion([sujeto(['Because', students, did, not, meet, the, daily, 'MVPA', 'recommendations,', some, strategies]), verbo([have]), complemento([been, provided, in, each, of, the, contexts, analyzed])]). relacion([sujeto(['Few', studies]), verbo([have]), complemento([examined, the, relationship, of, social, anxiety, with, drinking, game, participation])]). relacion([sujeto(['Socially', anxious, students, who, drank, to, cope, were, more, likely, to]), verbo([participate]), complemento([in, drinking, games, on, occasions, when, they, consumed, alcohol, than, those, who, did, not, endorse, this, drinking, motive])]). relacion([sujeto(['In', 'addition,', 'PrP(Sc)', was, partially, localized, in, astrocytes, and, 'microglia,']), verbo([suggesting]), complemento([that, these, cells, have, a, role, in, 'PrP(Sc)', 'processing,', degradation, or, both])]). relacion([sujeto(['Our', results, indicate, that, atypical, scrapie, is, transmissible, to, 'AL141RQ', 'sheep,', but, these, animals]), verbo([act]), complemento([as, clinically, silent, carriers, with, long, incubation, times])]). relacion([sujeto(['There', is, evidence, indicating, that, parent, training, programmes, including, interaction, coaching, of, parents, of, children, with, autism, spectrum, disorders, '(', 'ASD)', can]), verbo([increase]), complemento([parental, 'responsiveness,', promote, language, development, and, social, interaction, skills, in, children, with, 'ASD'])]). relacion([sujeto(['To', identify, the, speech]), verbo([acts]), complemento([of, healthcare, professionals, during, individual, 'video-recorded', interaction, coaching, sessions, of, a, 'Hanen-influenced', parent, training, programme, with, parents, of, children, with, 'ASD'])]). relacion([sujeto(['This', retrospective, study, used, speech]), verbo([act]), complemento([analysis])]). relacion([sujeto(['Sixteen', videos, were]), verbo([transcribed]), complemento([and, a, speech, act, analysis, was, conducted, to, identify, the, form, and, functions, of, the, language, used, by, the, healthcare, professionals])]). relacion([sujeto(['Descriptive', statistics]), verbo([provided]), complemento([frequencies, and, percentages, for, the, different, speech, acts, used, across, the, 16, videos])]). relacion([sujeto(['Six', types, of, speech]), verbo([acts]), complemento([used, by, the, healthcare, professionals, during, coaching, sessions, were, identified])]). relacion([sujeto(['These', speech]), verbo([acts]), complemento(['were,', in, order, of, 'frequency:', 'Instructing,', 'Modelling,', 'Suggesting,', 'Commanding,', 'Commending', and, 'Affirming'])]). relacion([sujeto(['The', healthcare, professionals, were]), verbo([found]), complemento([to, tailor, their, interaction, coaching, to, the, learning, needs, of, the, parents])]). relacion([sujeto(['A', pattern, was, observed, in, which, more, direct, speech]), verbo([acts]), complemento([were, used, in, instances, where, indirect, speech, acts, did, not, achieve, the, intended, response])]). relacion([sujeto(['The', study]), verbo([provides]), complemento([an, insight, into, the, nature, of, interaction, coaching, provided, by, healthcare, professionals, during, a, parent, training, programme])]). relacion([sujeto(['The', findings, may, be, used, to]), verbo([increase]), complemento([the, awareness, of, healthcare, professionals, about, the, types, of, speech, acts, used, during, interaction, coaching, as, well, as, the, manner, in, which, coaching, sessions, are, conducted])]). relacion([sujeto(['We', evaluated, fidelity, 'delivery,', 'receipt,', and, enactment, of, the, 48, -, week, 'Women\'s', 'Lifestyle', 'Physical', 'Activity', 'Program', conducted, to]), verbo([increase]), complemento([physical, activity, and, maintain, weight, in, 'African', 'American', women])]). relacion([sujeto(['Higher', group, meeting, attendance, was]), verbo([associated]), complemento([with, higher, accelerometer, steps, at, 24, weeks, and, lower, 'BMI', at, 24, and, 48, weeks])]). relacion([sujeto(['Breaking', periods, of, sitting, with, standing, may]), verbo([prevent]), complemento([chronic, diseases, and, increase, energy, expenditure, '(', 'EE)'])]). relacion([sujeto(['Sit-to-stand', height, adjustable, desks, may]), verbo([promote]), complemento([workplace, 'standing,', but, workers, have, to, be, willing, to, stand, for, portions, of, the, workday])]). relacion([sujeto(['Perceived', willingness, to, stand]), verbo([decreased]), complemento([from, 4.5, 'h/d', at, baseline, to, 3.4, 'h/d', after, 12, months])]). relacion([sujeto(['Standing', rather, than, sitting]), verbo([increased]), complemento(['EE', by, 7.5, 'kcal/h'])]). relacion([sujeto(['Use', of, a, height, adjustable, desk, for, 12, months, did, not, alter, the, hedonic, value, of, standing, or, 'sitting,', which, is, promising, for, 'long-term']), verbo([increases]), complemento([in, standing])]). relacion([sujeto(['Obesity', is, a, critical, problem, among, 'Mexican', 'youth,', but, few, studies]), verbo([have]), complemento([investigated, associations, among, physical, activity, '(', 'PA)', modes, and, anthropometrics, in, this, population])]). relacion([sujeto(['Parents', of, school, children, '(', 'N', =, 1996, ',', ages, 6, to, 14, 'years,', 53.1, '%', 'female)', in, 3, 'Mexican', cities]), verbo([reported]), complemento(['PA', participation, using, the, '(', 'modified)', fourth, grade, 'School', 'Physical', 'Activity', and, 'Nutrition', 'Survey'])]). relacion([sujeto(['Parents']), verbo([reported]), complemento([that, 52.3, '%', of, children, engaged, in, 'ACS,', 57.3, '%', participated, in, sports, or, organized, 'PA,', and, a, median, of, 2, days, in, the, previous, week, with, at, least, 30, minutes, of, outdoor, play])]). relacion([sujeto(['In', complete, case, analyses, '(', n, =, 857, ')', ',', 'ACS', was, negatively]), verbo([associated]), complemento([with, 'BMI', 'percentile,', and, outdoor, play, was, negatively, associated, with, 'WC', after, adjusting, for, 'school,', 'age,', 'sex,', and, income])]). relacion([sujeto(['In', analyses, incorporating, data, from, multiple, imputation, '(', 'N', =, 1996, ')', ',', outdoor, play, was, negatively]), verbo([associated]), complemento([with, 'WC', '(', all, 'Ps', &, 'lt;'])]). relacion([sujeto(['ACS', and, outdoor, play, are, favorably]), verbo([associated]), complemento([with, anthropometrics, and, may, help, prevent, childhood, obesity, in, 'Mexico'])]). relacion([sujeto(['ACS', and, outdoor, play, should, be, priorities, for]), verbo([increasing]), complemento([youth, 'PA', in, 'Mexico'])]). relacion([sujeto(['Parent', support, for, child, physical, activity, is, a, consistent, predictor, of]), verbo([increased]), complemento([childhood, activity])]). relacion([sujeto(['Little', is, known, about, factors, that]), verbo([prevent]), complemento([or, facilitate, support])]). relacion([sujeto(['A', 'cross-sectional', study, assessed, parents, whose, children]), verbo([participated]), complemento([in, 'Coronary', 'Artery', 'Risk', 'Detection', in, 'Appalachian', 'Communities', '(', 'CARDIAC)', screenings, in, a, rural, 'Appalachian', state])]). relacion([sujeto(['Rural', and, 'low-income', parents]), verbo([reported]), complemento([significantly, higher, barriers])]). relacion([sujeto(['Parents', of, girls]), verbo([reported]), complemento([a, higher, percentage, of, barriers, related, to, safety])]). relacion([sujeto(['Reported', barriers, in, this, sample, differed, from, those]), verbo([reported]), complemento([elsewhere, '(', 'Davison,', 2009, ')'])]). relacion([sujeto(['Specific', groups, such, as, 'low-income', and, rural, parents, should, be]), verbo([targeted]), complemento([in, intervention, efforts])]). relacion([sujeto(['Future', research, should, explore, gender, differences, in]), verbo([reported]), complemento([barriers, to, determine, the, influence, of, cultural, stereotypes])]). relacion([sujeto(['Physical', activity, '(', 'PA)']), verbo([has]), complemento([beneficial, effects, on, older, age, physical, 'functioning,', but, longitudinal, studies, with, 'follow-ups', extending, up, to, decades, are, few])]). relacion([sujeto(['The', study]), verbo([involved]), complemento([1260, people, aged, 60, to, 79, years, who, took, part, in, assessments, of, physical, functioning, '(', 'Short', 'Physical', 'Performance', 'Battery', '[', 'SPPB]', 'test,', 10, -, m, maximal, walking, 'test,', and, grip, strength, 'test)'])]). relacion([sujeto(['A', high, level, of, 'LTPA', earlier, in, life, was]), verbo([associated]), complemento([with, a, lower, risk, of, having, difficulties, on, the, 'SPPB', test, '(', odds, ratio, '[', 'OR]:', 0.37, ;, 95, '%', confidence, interval, '[', 'CI],', 0.24, -, 0.58, ')', and, especially, on, the, chair, rise, test, '(', 'OR:', 0.42, ;, 95, '%', 'CI,', 0.27, -, 0.64, ')', in, old, age])]). relacion([sujeto(['This', study, highlights, the, importance, of, 'LTPA', on, later, life, 'functioning,', but, also, indicates, the, inverse, effects, that, may, be]), verbo([caused]), complemento([by, heavy, manual, work])]). relacion([sujeto(['The', role, of, psychosocial, stress, in, the, development, of, obesity, and, metabolic, syndrome, is, receiving]), verbo([increased]), complemento([attention, and, has, led, to, examination, of, whether, physical, activity, may, moderate, the, 'stress-metabolic', syndrome, relationship])]). relacion([sujeto(['Although', stress, was, not]), verbo([associated]), complemento([with, 'MetS', '(', β, =, -])]). relacion([sujeto(['Strong', relationships, between, physical, activity, and, stress, with, 'MetS', or, 'BMI', were, not]), verbo([found]), complemento([in, this, sample])]). relacion([sujeto(['Parents\'', perception, of, neighborhood, safety, for, outside, play, can, deter, or]), verbo([promote]), complemento(['children\'s', physical, activity, and, use, of, recreational, facilities])]). relacion([sujeto(['Among', the, specific, 'problems,', only, obesity]), verbo([increased]), complemento([in, rank, from, 14, th, to, ninth, place])]). relacion([sujeto(['Three', variables, fell, more, than, 2, 'places:']), verbo([increasing]), complemento([traffic, '(', fifth, to, seventh, 'place),', poorly, planned, development, and, sprawl, '(', seventh, to, 11, th, 'place)', and, pedestrian, safety, '(', 12, th, to, 17, th, 'place)'])]). relacion([sujeto(['Across', 'years,', obesity, concerns]), verbo([have]), complemento([increased, but, do, not, appear, to, be, tied, to, increases, in, concern, for, 'ALC', variables])]). relacion([sujeto(['The', purpose, of, this, study, was, to, compare, the, physical, activity, parenting, practices, '(', 'PAPPs)', parents]), verbo([report]), complemento([using, with, the, 'PAPPs', incorporated, in, the, published, literature])]). relacion([sujeto(['The', extent, to, which, putting, more, emphasis, on, the, areas, identified, by, parents, will]), verbo([increase]), complemento([the, predictive, validity, of, the, measures, warrants, further, examination])]). relacion([sujeto(['The', number, of, injuries, during, the, past, 12, months, was]), verbo([reported]), complemento([16, months, after, baseline])]). relacion([sujeto(['Among', 'conscripts,', 48.5, '%']), verbo([reported]), complemento([at, least, 1, injury, for, the, past, 12, months])]). relacion([sujeto(['Independent', of, activity, 'level,', sensation, seeking]), verbo([increased]), complemento([cumulative, injury, incidence, significantly, '(', 'Logistic', regression, analysis, '[', injured, vs])]). relacion([sujeto(['Aggression', was, marginally]), verbo([associated]), complemento([only, with, cumulative, injury, incidence, and, only, in, those, participating, in, daily, sports])]). relacion([sujeto(['No', difference, was]), verbo([found]), complemento([in, body, mass, 'index,', muscle, 'strength,', and, the, overall, score, of, gross, and, fine, 'MC'])]). relacion([sujeto([36, ')', and]), verbo([reported]), complemento([significantly, more, sedentary, and, fewer, physical, activities, than, rural, children])]). relacion([sujeto(['Living', environment, was]), verbo([associated]), complemento([with, certain, components, of, 'HRF,', 'MC,', and, physical, and, sedentary, activities, of, 7, -, 'year-old', children, in, 'Suriname'])]). relacion([sujeto(['Further', research, is, needed, to, evaluate, the, development, of, urban, children, to]), verbo([provide]), complemento([information, for, possible, intervention, and, prevention, strategies])]). relacion([sujeto(['A', quasiexperimental, study, with, nonrandom, assignment, was, performed, to, evaluate, the, effectiveness, and, feasibility, of, a, 'school-based', physical, education, intervention, aimed, at]), verbo([increasing]), complemento([the, levels, of, 'moderate-to-vigorous', physical, activity, '(', 'MVPA)'])]). relacion([sujeto(['The', differences, observed, by, gender, highlight, the, need, to, use, different, strategies, to]), verbo([increase]), complemento([the, involvement, of, all, the, participants])]). relacion([sujeto(['The', 'Newman\'s', 'Every', 'Child', a, 'Sports', 'Person', '(', 'NECaSP)', intervention, aspires, to]), verbo([increase]), complemento([sport, and, physical, activity, '(', 'PA)', participation, among, young, people, in, the, 'United', 'Kingdom'])]). relacion([sujeto(['The', aims, of, this, article, are, to]), verbo([report]), complemento([on, a, summative, process, evaluation, of, the, 'NECaSP', and, make, recommendations, for, future, interventions])]). relacion([sujeto(['Seventeen', schools]), verbo([provided]), complemento([data, from, students, aged, 11, to, 13, years, '(', n, =, 1226, ')', ',', parents, '(', n, =, 192, ')', ',', and, teachers, '(', n, =, 14, ')', via, direct, observation, and, questionnaires])]). relacion([sujeto(['Data', highlighted, the, need, to, engage, parents, to]), verbo([increase]), complemento([the, likelihood, of, intervention, success])]). relacion([sujeto(['Finally,', changes, in, the, school, curriculum, can, be, successful, once, all, parties, are]), verbo([involved]), complemento(['(', 'community,', 'school,', 'families)'])]). relacion([sujeto(['Few', studies]), verbo([have]), complemento([used, ecological, models, to, study, multiple, levels, of, association, with, objectively, measured, 'moderate-to-vigorous', physical, activity, '(', 'MVPA)', in, young, children, from, 'middle-income', countries])]). relacion([sujeto(['The', human, colorectal, cancer, cell, lines, 'HCT116,', 'SW480,', 'DLD1,', and, 'KM12SM', were, engineered, to, stably]), verbo([express]), complemento([a, green, fluorescent, molecule, fused, to, the, degron, of, ornithine, 'decarboxylase,', resulting, in, an, accumulation, of, the, fluorescence, in, 'LPACs'])]). relacion([sujeto(['Treatment', resistance, '(', 'radio-', and, 'chemotherapy)', and, the, capacity, of, 'LPACs', to]), verbo([act]), complemento([as, 'CSCs', were, analyzed])]). relacion([sujeto(['Microarray', analysis, was, performed, to]), verbo([reveal]), complemento([genes, related, to, treatment, resistance])]). relacion([sujeto(['LPACs', had, a, significantly]), verbo([increased]), complemento([capacity, for, radioresistance, and, chemoresistance, '(', 5, -, fluorouracil, and, 'oxaliplatin),', significantly, lower, reactive, oxygen, species, 'activity,', and, significantly, increased, sphere, formation, capacity, compared, with, 'non-LPACs'])]). relacion([sujeto(['Subcutaneous', injection, of, as, few, as, 20, 'LPACs']), verbo([led]), complemento([to, tumor, formation, in, immunologically, incompetent, mice])]). relacion([sujeto(['Microarray', analysis, revealed, that, the, expression, of, 'EP300-interacting', inhibitor, of, differentiation, 3, '(', 'EID3)', was, significantly]), verbo([increased]), complemento([in, 'LPACs'])]). relacion([sujeto(['LPACs']), verbo([have]), complemento([characteristic, treatment, resistance, and, act, as, 'CSCs', in, colorectal, cancer])]). relacion([sujeto(['Cisplatin', is, an, effective, anticancer, 'drug;', 'however,', cisplatin, use, often]), verbo([leads]), complemento([to, 'nephrotoxicity,', which, limits, its, clinical, effectiveness])]). relacion([sujeto(['Pretreatment', with, dichloroacetate, significantly, attenuated, the, 'cisplatin-induced']), verbo([increase]), complemento([in, 'BUN', and, serum, creatinine, 'levels,', renal, tubular, 'apoptosis,', and, oxidative, stress])]). relacion([sujeto(['Whole', transcriptome, sequencing, revealed, that, dichloroacetate]), verbo([prevented]), complemento([mitochondrial, dysfunction, and, preserved, the, 'energy-generating', capacity, of, the, kidneys, by, preventing, the, 'cisplatin-induced', downregulation, of, fatty, acid, and, glucose, 'oxidation,', and, of, genes, involved, in, the, 'Krebs', cycle, and, oxidative, phosphorylation])]). relacion([sujeto(['These', data]), verbo([provide]), complemento([strong, evidence, that, dichloroacetate, preserves, renal, function, when, used, in, conjunction, with, cisplatin])]). relacion([sujeto(['Current', bullying, was]), verbo([reported]), complemento([by, 7.0, '%', of, 'respondents,', while, 46.4, '%', of, respondents, reported, that, they, had, been, bullied, at, some, point, in, their, working, life])]). relacion([sujeto(['This', study]), verbo([provides]), complemento([unique, information, on, the, prevalence, and, mental, health, impacts, of, workplace, bullying, and, 'ill-treatment', in, 'Australia'])]). relacion([sujeto(['Workplace', bullying, is, a, relatively, common, 'experience,', and, is]), verbo([associated]), complemento([with, increased, risk, of, depression, and, anxiety])]). relacion([sujeto(['Greater', attention, to, identifying, and]), verbo([preventing]), complemento([bullying, and, 'ill-treatment', in, the, workplace, is, warranted])]). relacion([sujeto(['In', 'England', and, 'Wales,', the, 'Approved', 'Mental', 'Health', 'Professional', '(', 'AMHP)']), verbo([has]), complemento([final, responsibility, for, applying, under, the, 'Mental', 'Health', 'Act', 1983, to, admit, an, individual, compulsorily, and, convey, them, to, psychiatric, hospital])]). relacion([sujeto(['Participants', identify, career, progression, and, professional, development, as, significant, as, well, as, the, status, and, independence, of, the, role, and]), verbo([enhanced]), complemento([job, security])]). relacion([sujeto(['AMHPs', are, motivated, by, an]), verbo([increase]), complemento([in, professional, status, and, job, 'security,', but, also, exercising, independent, judgment, and, authority, in, a, 'time-limited', intervention, is, emotionally, and, professionally, rewarding])]). relacion([sujeto(['Conflicting', results, on, the, role, of, secreted, protein, acidic, and, rich, in, cysteins, '(', 'SPARC)', expression]), verbo([have]), complemento([been, reported, in, resected, pancreatic, ductal, adenocarcinoma, '(', 'PDAC),', and, its, prognostic, 'and/or', predictive, role, in, advanced, 'PDAC', '(', 'aPDAC)', has, not, been, extensively, investigated, yet])]). relacion([sujeto([',', 'cytoplasmic)', 'SPARC', expression, in, tumour, tissue, '(', primary, tumours, and, 'metastases)', of, 134, aPDAC, pts]), verbo([participating]), complemento([in, completed, prospective, clinical, and, biomarker, trials])]). relacion([sujeto(['Sixty-seven', per, cent, of, the, analysed, tumours, showed, high, stromal, 'SPARC', 'expression,', which, was, not]), verbo([associated]), complemento([with, overall, survival, '(', 'OS,', median, 9.1, vs, 7.6, 'months,', 'P=0'])]). relacion([sujeto(['In', pts, receiving, 'gemcitabine-based', chemotherapy, cytoplasmic, 'SPARC', expression, was, significantly]), verbo([associated]), complemento([with, an, inferior, 'PFS', and, 'OS', '(', 'PFS:', 6.2, vs, 9.2, 'months,', 'P=0'])]). relacion([sujeto(['We', identified, cytoplasmic, 'SPARC', expression, in, the, primary, tumour, as, a, biomarker]), verbo([associated]), complemento([with, inferior, 'PFS', and, 'OS', in, aPDAC])]). relacion([sujeto(['Cytoplasmic', 'SPARC', expression, may, furthermore]), verbo([act]), complemento([as, a, negative, predictive, biomarker, in, pts, treated, with, 'gemcitabine-based', chemotherapy])]). relacion([sujeto(['Near-infrared', spectroscopy, estimates, cerebral, regional, tissue, oxygen, saturation, '(', 'rSO2),', which, may]), verbo([decrease]), complemento([under, hyperventilation])]). relacion([sujeto(['Propofol', and, sevoflurane]), verbo([act]), complemento([differently, on, cerebral, blood, vessels])]). relacion([sujeto([10, trial, patients, through, a, 'hypothesis-driven', 'analysis,', and, showed, that, 'MMS19', levels]), verbo([associated]), complemento([with, 'ACT', benefit])]). relacion([sujeto(['The', transmission, of, extracellular, signals, into, the, nucleus]), verbo([involves]), complemento([inducible, transcription, 'factors,', but, how, different, signalling, pathways, act, in, a, cell, 'type-specific', fashion, is, poorly, understood])]). relacion([sujeto(['Here,', we, studied, the, regulatory, role, of, the, 'AP-1', transcription, factor, family, in, blood, development, using, embryonic, stem, cell, differentiation, coupled, with, 'genome-wide', transcription, factor]), verbo([binding]), complemento([and, gene, expression, analyses])]). relacion([sujeto(['AP-1', factors]), verbo([respond]), complemento([to, 'MAP', kinase, signalling, and, comprise, dimers, of, 'FOS,', 'ATF', and, 'JUN', proteins])]). relacion([sujeto(['To', examine, genes]), verbo([regulated]), complemento([by, 'AP-1', and, to, examine, how, it, interacts, with, other, inducible, transcription, 'factors,', we, abrogated, its, global, 'DNA-binding', activity, using, a, 'dominant-negative', 'FOS', peptide])]). relacion([sujeto(['We', show, that, 'FOS', and, 'JUN']), verbo([bind]), complemento([to, and, activate, a, specific, set, of, vascular, genes, and, that, 'AP-1', inhibition, shifts, the, balance, between, smooth, muscle, and, hematopoietic, differentiation, towards, blood])]). relacion([sujeto(['Furthermore,', 'AP-1', is]), verbo([required]), complemento([for, de, novo, binding, of, 'TEAD4,', a, transcription, factor, connected, to, 'Hippo', signalling])]). relacion([sujeto(['Our', 'bottom-up', approach, demonstrates, that, 'AP-1-', and, 'TEAD4-associated', 'cis-regulatory', elements, form, hubs, for, multiple, 'signalling-responsive', transcription, factors, and, define, the, cistrome, that]), verbo([regulates]), complemento([vascular, and, hematopoietic, development, by, extrinsic, signals])]). relacion([sujeto(['The', microtubule, cytoskeleton]), verbo([regulates]), complemento([cell, polarity, by, spatially, organizing, membrane, trafficking, and, signaling, processes])]). relacion([sujeto(['In', epithelial, 'cells,', microtubules, form, parallel, arrays, aligned, along, the, 'apico-basal', 'axis,', and, recent, work]), verbo([has]), complemento([demonstrated, that, the, members, of, 'CAMSAP/Patronin', family, control, apical, tethering, of, microtubule, minus, ends])]). relacion([sujeto(['Here,', we, show, that, in, mammalian, intestinal, epithelial, 'cells,', the, spectraplakin, 'ACF7', '(', also, known, as, 'MACF1)', specifically]), verbo([binds]), complemento([to, 'CAMSAP3', and, is, required, for, the, apical, localization, of, 'CAMSAP3-decorated', microtubule, minus, ends])]). relacion([sujeto(['In', 'short-term', epithelial, polarization, 'assays,', knockout, of, 'CAMSAP3,', but, not, of, 'CAMSAP2,']), verbo([caused]), complemento([microtubule, 're-organization', into, a, more, radial, centrosomal, 'array,', redistribution, of, 'Rab11-positive', '(', also, known, as, 'Rab11A)', endosomes, from, the, apical, cell, surface, to, the, pericentrosomal, region, and, inhibition, of, actin, brush, border, formation, at, the, apical, side, of, the, cell])]). relacion([sujeto(['We', conclude, that, 'ACF7', is, an, important, regulator, of, 'apico-basal', polarity, in, mammalian, intestinal, cells, and, that, a, radial, 'centrosome-centered', microtubule, organization, can]), verbo([act]), complemento([as, an, inhibitor, of, epithelial, polarity])]). relacion([sujeto(['The', intestinal, epithelium, is, the, fastest, renewing, tissue, in, mammals, and]), verbo([has]), complemento([a, large, flexibility, to, adapt, to, different, types, of, damage])]). relacion([sujeto(['Lgr5(+)', crypt, base, columnar, '(', 'CBC)', cells]), verbo([act]), complemento([as, stem, cells, during, homeostasis, and, are, essential, during, regeneration])]). relacion([sujeto(['Upon', 'perturbation,', the, activity, of, 'CBCs', is, dynamically]), verbo([regulated]), complemento([to, maintain, homeostasis, and, multiple, dedicated, progenitor, cell, populations, can, reverse, to, the, stem, cell, state, upon, 'damage,', adding, another, layer, of, compensatory, mechanisms, to, facilitate, regeneration])]). relacion([sujeto(['Here,', we, review, our, current, understanding, of, how, intestinal, stem, and, progenitor, cells, contribute, to, homeostasis, and, 'regeneration,', and, the, different, signaling, pathways, that]), verbo([regulate]), complemento([their, behavior])]). relacion([sujeto(['Nutritional', state, and, inflammation]), verbo([have]), complemento([been, recently, identified, as, upstream, regulators, of, stem, cell, activity, in, the, mammalian, 'intestine,', and, we, explore, how, these, systemic, signals, can, influence, homeostasis, and, regeneration])]). relacion([sujeto(['Recently,', a, 'Portugese', questionnaire]), verbo([has]), complemento([been, developed, '\'', 'The', 'Control', of, 'Allergic', 'Rhinitis', and, 'Asthma', 'Test\'', '(', 'CARATkids)', that, measures, disease, control, of, both, diseases, in, children])]). relacion([sujeto(['Here,', we]), verbo([report]), complemento([that, '(', 1, ')', the, 'ORCA', gene, cluster, is, differentially, 'regulated;', '(', 2, ')', 'ORCA4,', while, overlapping, functionally, with, 'ORCA3,', modulates, an, additional, set, of, 'TIA', genes])]). relacion([sujeto(['Unlike', 'ORCA3,', 'ORCA4', overexpression, resulted, in, dramatic]), verbo([increase]), complemento([of, 'TIA', accumulation, in, 'C'])]). relacion([sujeto(['In', 'addition,', 'CrMYC2', is, capable, of]), verbo([activating]), complemento(['ORCA3', and, 'co-regulating', 'TIA', pathway, genes, concomitantly, with, 'ORCA3'])]). relacion([sujeto(['The', 'ORCA', gene, cluster, and, 'CrMYC2']), verbo([act]), complemento([downstream, of, a, 'MAP', kinase, cascade, that, includes, a, previously, uncharacterized, 'MAP', kinase, 'kinase,', 'CrMAPKK1'])]). relacion([sujeto([&, 'nbsp;roseus', hairy, roots, upregulated, 'TIA', pathways, genes, and]), verbo([increased]), complemento(['TIA', accumulation])]). relacion([sujeto(['This', work]), verbo([provides]), complemento([detailed, characterization, of, a, 'TF', gene, cluster, and, advances, our, understanding, of, the, transcriptional, and, 'post-translational', regulatory, mechanisms, that, govern, 'TIA', biosynthesis, in, 'C'])]). relacion([sujeto(['Although', 'co-payments', and, deductibles, are, means, of, keeping, health, expenditures, 'low,', they]), verbo([have]), complemento([also, been, cited, as, barriers, that, inhibit, patients, from, accessing, necessary, healthcare])]). relacion([sujeto(['We']), verbo([found]), complemento([that, 40, '%', of, respondents, had, a, 'co-pay', of, '$20-$50,', while, 35.7, '%', of, respondents, had, a, deductible, of, greater, than, '$500'])]). relacion([sujeto(['Therefore,', a, crucial, strategy, to]), verbo([maintain]), complemento([a, good, health, status, is, to, identify, molecules, capable, of, offering, protection, against, 'OS', through, chemical, routes])]). relacion([sujeto(['Unfortunately,', they]), verbo([have]), complemento([been, less, investigated, than, 'phenols,', 'MLT', and, its, 'non-phenolic', metabolites, in, this, context])]). relacion([sujeto(['The', evidence, reviewed, here, strongly]), verbo([suggests]), complemento([that, 'MLT', phenolic, derivatives, can, act, as, both, primary, and, secondary, 'antioxidants,', exerting, their, protection, through, diverse, chemical, routes])]). relacion([sujeto(['Due', to, its, good, electric, 'conductivity,', large, specific, surface, 'area,', and, excellent, mechanical, 'properties,', 'TCPP-Gr/AuNPs', can]), verbo([act]), complemento([as, an, enhanced, material, for, the, electrochemical, detection, of, myoglobin])]). relacion([sujeto(['Meanwhile,', it]), verbo([provides]), complemento([an, effective, matrix, for, immobilizing, 'myoglobin-binding', aptamer, '(', 'MbBA)'])]). relacion([sujeto(['The', electrochemical, aptasensor]), verbo([has]), complemento([a, sensitive, response, to, myoglobin, in, a, linear, range, from, 2.0, ×, 10, '(', -, 11, ')', 'M', to, 7.7, ×, 10, '(', -, 7, ')', 'M', with, a, detection, limit, of, 6.7, ×, 10, '(', -, 12, ')', 'M', '(', 'S/N', =, 3, ')'])]). relacion([sujeto(['Furthermore,', the, method]), verbo([has]), complemento([the, merits, of, high, 'sensitivity,', low, 'price,', and, high, specificity])]). relacion([sujeto(['The', ability, of, zinc, cations, to, develop, different, linkages, with, 'starch\'s', hydrophilic, functional, groups, and, to]), verbo([act]), complemento([as, external, nucleators, determines, an, increase, in, 'HTC', 'yield;', the, effect, is, obvious, even, in, the, presence, of, small, concentrations, of, zinc, in, the, reaction, medium, '(', 0.005, 'M),', thus, providing, a, way, to, improve, the, carbonization, process, efficiency])]). relacion([sujeto(['It', is, also, shown, that, zinc, content, is, the, control, vector, of, the, spherical, 'composite\'s', 'properties:', a, variation, from, 0.3, to, 4.8, 'at%', not, only]), verbo([induces]), complemento([a, variation, in, their, size, '(', 200, 'nm-10', 'μm),', interconnectivity, '(', from, disperse, spheres, to, 'necklace-like', 'aggregations),', surface, area, and, connected, porosity, '(', from, 'micro-', to, 'mesoporosity),', but, also, of, their, electrochemical, and, white, light, adsorption, and, emission, features])]). relacion([sujeto(['Since', the, variation, in, zinc, content, is, made, by, a, simple, adjustment, of, the, raw, material, 'concentrations,', the, functionality, of, these, 'carbon-based', materials, can, be]), verbo([modulated]), complemento([in, a, straightforward, manner])]). relacion([sujeto(['Both', these, molecules]), verbo([have]), complemento([an, aryl, sulfonamide, for, reversible, binding, with, 'Human', 'Carbonic', 'Anhydrase', 'II', '(', 'HCA', 'II)', and, a, pyrene, moiety, for, the, visualization, of, a, capture, event])]). relacion([sujeto(['While', compound, 1]), verbo([has]), complemento([an, aryl, azide, as, a, photo, 'cross-linking', 'agent,', compound, 2, lacks, the, azide, moiety])]). relacion([sujeto(['This', observation, demonstrates, the, ability, of, the, enediyne, moiety, to]), verbo([act]), complemento([as, a, 'photo-affinity', label, possibly, via, the, addition, of, nucleophilic, amino, acids, to, the, partially, zwitterionic, singlet, form, of, the, diradical, generated, by, photo, 'Bergman', cyclization])]). relacion([sujeto(['Most', of, the, publications]), verbo([have]), complemento([focused, on, descriptive, 'epidemiology,', management, 'practices,', 'worker\'s', 'knowledge,', 'attitude,', 'training,', and, rehabilitation, services])]). relacion([sujeto(['The', 'transportation,', agriculture, and, construction, sectors, were]), verbo([found]), complemento([to, be, the, most, hazardous, sectors, and, would, benefit, the, most, from, 'Occupational', 'Safety', &, 'amp;', 'Health', '(', 'OSH)', research, and, interventions])]). relacion([sujeto(['There', is, a, strong, need, to, develop, a, national, injury, surveillance, system, and, also, a, mechanism, to]), verbo([ensure]), complemento([adherence, to, the, 'Occupational', 'Safety', &, 'amp;', 'Health', 'Act(OSHA)', 1994])]). relacion([sujeto(['Bacterial', 'non-coding', 'RNAs']), verbo([act]), complemento([by, 'base-pairing', as, regulatory, elements, in, crucial, biological, processes])]). relacion([sujeto(['We', performed, the, identification, of, 'trans-encoded', small, 'RNAs', '(', 'sRNA)', from, the, genomes, of, 'Mycoplama', 'hyopneumoniae,', 'Mycoplasma', flocculare, and, 'Mycoplasma', 'hyorhinis,', which, are, 'Mycoplasma', species, that]), verbo([have]), complemento([been, identified, in, the, porcine, respiratory, system])]). relacion([sujeto(['All', tested, sRNAs, were]), verbo([transcribed]), complemento([in, at, least, one, condition])]). relacion([sujeto([hyopneumoniae, sRNAs, in, response, to, oxidative, and, heat, shock, stress, 'conditions,']), verbo([suggesting]), complemento([that, their, expression, is, influenced, by, environmental, signals])]). relacion([sujeto(['Moreover,', we, analyzed, 'sRNA-mRNA', hybrids, and, accessed, putative]), verbo([target]), complemento([genes, for, the, novel, sRNA, candidates])]). relacion([sujeto(['The', majority, of, the, sRNAs, showed, interaction, with, multiple]), verbo([target]), complemento(['genes,', some, of, which, could, be, linked, to, pathogenesis, and, cell, homeostasis, activity])]). relacion([sujeto(['Furthermore,', the, mRNA]), verbo([target]), complemento([prediction, provides, a, perspective, for, the, characterization, and, comprehension, of, the, function, of, the, sRNA, regulatory, mechanisms])]). relacion([sujeto(['Here,', we]), verbo([provide]), complemento([information, concerning, a, critical, step, in, the, 'oxygen-evolving,', or, 'S-state,', cycle])]). relacion([sujeto(['During', this, 'S3-to-S0', 'transition,', oxygen, is, 'produced,', and, substrate, water]), verbo([binds]), complemento([to, the, 'manganese-calcium', catalytic, site])]). relacion([sujeto(['Our', spectroscopic, and, 'H2(18)O', labeling, experiments, show, that, this, 'S3-to-S0', step, is]), verbo([associated]), complemento([with, the, protonation, of, an, internal, water, cluster, in, a, 'hydrogen-bonding', 'network,', which, contains, calcium])]). relacion([sujeto(['This', evidence, shows, that, internal, water, and, the, hydrogen, bonding, network]), verbo([act]), complemento([as, a, transient, proton, acceptor, at, multiple, points, in, the, 'oxygen-evolving', cycle])]). relacion([sujeto(['This', paper, highlights, two, of, 'those:', '(', 1, ')', 'marketing,', 'admission,', and, matriculation, across, two, 'programs,', and, '(', 2, ')']), verbo([enhancing]), complemento([curricula, through, distance, coursework, and, interprofessional, education])]). relacion([sujeto(['Current', drugs, against, the, influenza, 'A', virus, '(', 'IAV)']), verbo([act]), complemento([by, inhibiting, viral, neuraminidase, '(', 'NA)', enzymes, responsible, for, the, release, of, budding, virions, from, sialoglycans, on, infected, cells])]). relacion([sujeto(['Here,', we, describe, an, approach, focused, on, a, search, for, inhibitors, that, reinforce, the, protective, functions, of, mucosal, barriers, that, trap, viruses, en, route, to, the]), verbo([target]), complemento([cells])]). relacion([sujeto(['We']), verbo([have]), complemento([generated, mimetics, of, 'sialo-glycoproteins', that, insert, into, the, viral, envelope, to, provide, a, 'well-defined', 'mucus-like', environment, encapsulating, the, virus])]). relacion([sujeto(['By', introducing, this, 'barrier,', which, the, virus, must, breach, using, its, 'NA', enzymes, to, infect, a, host, 'cell,', into, a, screening, 'platform,', we]), verbo([have]), complemento([been, able, to, identify, compounds, that, provide, significant, protection, against, 'IAV', infection])]). relacion([sujeto(['Recent', 'large-scale', phenotypic, screens]), verbo([have]), complemento([provided, a, wealth, of, potential, starting, points, for, 'hit-to-lead', campaigns])]). relacion([sujeto(['One', chemical, subseries, was]), verbo([found]), complemento([to, exhibit, oral, activity, but, contained, a, labile, ester, that, could, not, be, replaced, without, loss, of, 'activity,', and, the, original, hit, exhibited, remarkable, sensitivity, to, minor, structural, change])]). relacion([sujeto(['Mesangiogenic', 'Progenitor', 'Cells', '(', 'MPCs)', are, human, bone, 'marrow-derived', multipotent, 'cells,', isolated, in, vitro, under, selective, culture, conditions, and, shown, to]), verbo([retain]), complemento([both, mesengenic, and, angiogenic, potential])]). relacion([sujeto(['In', the, present, paper, we, screened, different, sources, of, commercially, available, pooled, human, 'AB', type, serum, '(', 'PhABS)', for, their, ability, to]), verbo([promote]), complemento(['MPC', production, under, selective, culture, conditions])]). relacion([sujeto(['Therefore,', we, tested, a, number, of, growth, factors, '(', 'hGF)', and]), verbo([found]), complemento([that, higher, concentrations, of, 'FGF-2,', 'EGF,', 'PDGF-AB,', and, 'VEGF-A', as, well, as, lower, concentration, of, 'IGF-1', give, 'sub-optimal', 'MPC', recovery])]). relacion([sujeto(['Gene', expression, analysis, of, hGF, receptors, was, also, carried, out, both, in, 'MSCs', and, 'MPCs,']), verbo([suggesting]), complemento([that, 'FGF-2,', 'EGF,', and, 'PDGF-AB', could, act, promoting, 'MSC', 'proliferation,', while, 'VEGF-A', contribute, to, 'MSC-like', cell, 'contamination,', triggering, 'MPC', differentiation])]). relacion([sujeto(['Transmuscular', migration, of, the, encircling, band, through, rectus, muscles, and, straddling, of, the, cornea]), verbo([has]), complemento([only, been, reported, in, a, few, cases, previously, in, the, literature])]). relacion([sujeto(['This', rare, condition]), verbo([has]), complemento([never, been, associated, with, glaucoma])]). relacion([sujeto(['In', this, 'report,', we, aimed, to, describe, a, unique, case, with, transmuscular, migration, of, encircling, buckle, as, a, probable]), verbo([cause]), complemento([of, glaucoma])]). relacion([sujeto(['Transmuscular', migration, of, the, encircling, band, through, rectus, muscles, and, straddling, of, the, cornea, may]), verbo([act]), complemento([as, a, trigger, for, glaucoma])]). relacion([sujeto(['kurdica,']), verbo([have]), complemento([led, to, reduced, microbial, 'growth,', and, these, herbs, also, have, a, particular, effect, on, the, production, of, aflatoxins, as, carcinogenic, compounds])]). relacion([sujeto([kurdica, as, a, natural, compound, used, to]), verbo([inhibit]), complemento([the, growth, of, 'A'])]). relacion([sujeto([parasiticus, and, to]), verbo([act]), complemento([as, an, 'anti-mycotoxin'])]). relacion([sujeto([kurdica, can]), verbo([inhibit]), complemento(['A'])]). relacion([sujeto(['HPLC', results, revealed, a, significant]), verbo([decrease]), complemento([in, aflatoxin, production, with, 125, 'mg/mL', of, 'P'])]). relacion([sujeto(['Based', on, quantitative, 'real-time', 'PCR', 'results,', the, rate, of, aflR, gene, expression, was, significantly]), verbo([decreased]), complemento([after, treatment, with, 'P'])]). relacion([sujeto([kurdica]), verbo([has]), complemento(['anti-toxic', properties, in, addition, to, an, inhibitory, effect, on, 'A'])]). relacion([sujeto([parasiticus, 'growth,', and, is, able, to]), verbo([decrease]), complemento([aflatoxin, production, effectively, in, a, 'dose-dependent', manner])]). relacion([sujeto(['There', are, many, and, often, intricate]), verbo([causes]), complemento([for, aseptic, loosening])]). relacion([sujeto(['We', conducted, a, retrospective, study, of, 64, cases, with, aseptic, loosening, of, total, hip, prosthesis, to, individuate, 'patient,', implant, type, and, surgical, technique, related, factors]), verbo([leading]), complemento([to, aseptic, loosening, and, to, provide, recommendations, to, minimize, this, risk])]). relacion([sujeto(['Statistical', analysis, of, the, results, identified, risk, factors]), verbo([leading]), complemento([to, 'loosening,', such, 'as:', 'age,', body, mass, 'index,', level, of, 'activity,', cup, 'inclination,', femoral, offset, and, cementation, quality])]). relacion([sujeto(['A', significant, reduction, in, aseptic, loosening, of, total, hip, prostheses, may, only, be, achieved, by, a, more, rigorous, selection, of, 'patients,', a, greater, security, in, the, technical]), verbo([act]), complemento([and, a, better, choice, of, the, implant, to, be, placed])]). relacion([sujeto(['The', national, incidence, of, adverse, events, '(', 'AEs)', in, 'Swedish', orthopedic, care]), verbo([has]), complemento([never, been, described])]). relacion([sujeto(['A', new, national, database]), verbo([has]), complemento([made, it, possible, to, describe, 'incidence,', 'nature,', preventability, and, consequences, of, 'AEs', in, 'Swedish', orthopedic, care])]). relacion([sujeto(['Using', a, national, 'database,', we]), verbo([found]), complemento(['AEs', in, 15, &, 'nbsp;%', of, orthopedic, admissions])]). relacion([sujeto(['Here', we]), verbo([report]), complemento([data, where, we, assessed, esthetic, appreciation, of, music, after, 1])]). relacion([sujeto(['Data', are]), verbo([reported]), complemento([from, two, experiments, with, different, patient, 'groups:', 1])]). relacion([sujeto(['Participants', in, both, experiments, performed, 'Jymmin,', a, music, feedback, method, where, exercise, equipment, is, modified, in, such, a, way, that, it, can, be, played, like, musical, instruments, by]), verbo([modulating]), complemento([musical, parameters, in, a, composition, software])]). relacion([sujeto(['This', combines, physical, exertion, with, musical, performance, in, a, fashion, that]), verbo([has]), complemento([previously, been, shown, to, have, a, number, of, positive, psychological, effects, such, as, enhanced, mood, and, reduced, perceived, exertion])]). relacion([sujeto(['This']), verbo([suggests]), complemento([that, the, act, of, making, music, '(', when, combined, with, physical, 'exertion)', is, associated, with, a, positivity, bias, about, the, perceived, esthetical, quality, of, the, musical, outcome])]). relacion([sujeto(['This']), verbo([suggests]), complemento([that, musical, feedback, interventions, may, not, always, have, to, be, highly, individualized, because, individual, taste, may, not, always, be, crucial])]). relacion([sujeto(['The', results, also]), verbo([suggest]), complemento([that, the, method, applied, here, may, be, efficient, at, encouraging, music, listeners, to, actively, explore, new, musical, styles, that, they, might, otherwise, be, reluctant, to, listen, to, '(', e])]). relacion([sujeto(['The', results, also, hint, toward, a, deeper, understanding, of, why, 'musicians,', who, exert, themselves, physically, during, musical, performances, to, generate, music, and, regardless, of, the, type, of, music, they, are, 'playing,', typically]), verbo([find]), complemento([the, physically, demanding, experience, esthetically, satisfying])]). relacion([sujeto(['It']), verbo([has]), complemento([been, reported, that, fatty, acid, binding, proteins, '(', 'FABPs)', do, not, act, only, as, intracellular, mediators, of, lipid, responses, but, also, have, extracellular, functions])]). relacion([sujeto(['This', study, aimed, to, investigate, whether, extracellular, liver, type, '(', 'L)-FABP']), verbo([has]), complemento([a, biological, activity, and, to, determined, serum, 'L-FABP', levels, in, patients, with, 'end-stage', renal, disease, '(', 'ESRD)'])]). relacion([sujeto(['We', isolated, 'L-FABP', complementary, deoxyribonucleic, acid, '(', 'cDNA)', from, the, 'Huh7', human, hepatocarcinoma, cell, line, and]), verbo([expressed]), complemento([the, recombinant, 'L-FABP', protein, in, 'Escherichia', coli])]). relacion([sujeto(['A549', lung, carcinoma, and, 'THP-1', monocytic, cells, were]), verbo([stimulated]), complemento([with, the, human, recombinant, 'L-FABP'])]). relacion([sujeto(['Human', recombinant, 'L-FABP']), verbo([induced]), complemento(['IL-6', in, a, 'dose-dependent', manner, in, 'A549,', 'THP-1', 'cells,', and, whole, blood, cells])]). relacion([sujeto(['Our', results, demonstrated, the, biological, activity, of, 'L-FABP', in, human, cells]), verbo([suggesting]), complemento(['L-FABP', can, be, a, mediator, of, inflammation])]). relacion([sujeto(['Malaria-endemic', countries]), verbo([have]), complemento([implemented, community, health, worker, '(', 'CHW)', programs, to, provide, malaria, diagnosis, and, treatment, to, populations, living, beyond, the, reach, of, health, systems])]). relacion([sujeto(['All', 'CHWs', were, trained, to, prescribe, 'artemisinin-based', combination, therapy, '(', 'ACT)', for, malaria, and]), verbo([recognize]), complemento([signs, and, symptoms, for, referral, to, health, centers])]). relacion([sujeto(['CHWs', using, mRDTs, and, 'ACTs']), verbo([increased]), complemento([referral, compared, with, 'CHWs', using, a, presumptive, diagnosis])]). relacion([sujeto(['Although', 'IFNλ1,', 'IFNλ2,', and, 'IFNλ3']), verbo([act]), complemento(['antiviral,', genetic, association, studies, have, shown, that, expression, of, the, recently, discovered, 'IFNL4', is, detrimental, to, hepatitis, 'C', virus, '(', 'HCV)', infection, through, a, yet, unknown, mechanism])]). relacion([sujeto(['We']), verbo([found]), complemento([that, 'IFNλ4', exhibits, similar, antiviral, activity, to, 'IFNλ3', without, negatively, affecting, antiviral, 'IFN', activity, or, cell, survival])]). relacion([sujeto(['This', study]), verbo([provides]), complemento([mechanistic, evidence, that, humans, suppress, 'IFNλ4', 'expression,', suggesting, that, immune, function, is, dependent, on, other, 'IFNL', family, members])]). relacion([sujeto(['Peroxisomes', are, ubiquitous, eukaryotic, organelles, that, play, pivotal, roles, in, a, suite, of, metabolic, processes, and, often]), verbo([act]), complemento([coordinately, with, other, 'organelles,', such, as, chloroplasts, and, mitochondria])]). relacion([sujeto(['Peroxisomes', import, proteins, to, the, peroxisome, matrix, by, peroxins, '(', 'PEX', 'proteins),', but, how, the, function, of, the, 'PEX', proteins, is]), verbo([regulated]), complemento([is, poorly, understood])]). relacion([sujeto(['SP1']), verbo([interacts]), complemento([physically, with, the, two, components, of, the, peroxisome, protein, docking, complex, 'PEX13-PEX14', and, the, '(', 'RING)-finger', peroxin, 'PEX2'])]). relacion([sujeto(['Loss', of, 'SP1', function]), verbo([suppresses]), complemento([defects, of, the, 'pex14-2', and, 'pex13-1', 'mutants,', and, 'SP1', is, involved, in, the, degradation, of, 'PEX13', and, possibly, 'PEX14', and, all, three, 'RING', peroxins])]). relacion([sujeto(['An', in, vivo, ubiquitination, assay, showed, that, 'SP1']), verbo([has]), complemento([the, ability, to, promote, 'PEX13', ubiquitination])]). relacion([sujeto(['Our', study]), verbo([has]), complemento([revealed, 'that,', in, addition, to, its, previously, reported, function, in, chloroplast, 'biogenesis,', 'SP1', plays, a, role, in, peroxisome, biogenesis])]). relacion([sujeto(['The', same, 'E3', ubiquitin, ligase]), verbo([promotes]), complemento([the, destabilization, of, components, of, two, distinct, 'protein-import', 'machineries,', indicating, that, degradation, of, organelle, biogenesis, factors, by, the, 'ubiquitin-proteasome', system, may, constitute, an, important, regulatory, mechanism, in, coordinating, the, biogenesis, of, metabolically, linked, organelles, in, eukaryotes])]). relacion([sujeto(['Compared', with, the, conventional, 'approach,', 'Bayesian', optimization]), verbo([decreases]), complemento([the, uncertainties, in, 'B', by, 41, '%', and, in, 'O', by, 46, '%'])]). relacion([sujeto(['The', 'L', uncertainty]), verbo([decreases]), complemento([by, 47, '%', ',', whereas, 'F', uncertainty, is, marginally, improved, through, the, knowledge, of, natural, fluxes])]). relacion([sujeto(['Both', ocean, and, net, land, uptake, '(', 'B', +, 'L)', rates]), verbo([have]), complemento([positive, trends, of, 29, ±, 8, and, 37, ±, 17, 'Tg', 'C⋅y(-2)', since, 1980, ',', respectively])]). relacion([sujeto(['The', 'American', 'Society', for, 'Cell', 'Biology', 'Women', in, 'Cell', 'Biology', 'Sandra', 'Masur', 'Senior', 'Award']), verbo([recognizes]), complemento([leadership, in, scientific, accomplishments, and, in, 'mentoring,', which, are, intertwined])]). relacion([sujeto([&, 'quot;', 'In', 'turn,', as, an, established, 'investigator,', my, scientific, successes, in, researching, 1, ')', 'chromosomes,', their, replication, and, 'genomics,', and, 2, ')', 'ribosomes,', their, 'structure,', 'evolution,', and, 'biogenesis,', reflects, the, hard, work, of, my, students, and, 'postdocs,', for, whom, 'I']), verbo([act]), complemento([as, a, 'mentor,', guiding, them, in, their, research, and, along, their, career, paths])]). relacion([sujeto(['Herein,', we]), verbo([provide]), complemento([a, detailed, description, of, how, such, alterations, contribute, to, the, development, and, progression, of, 'CRPC'])]). relacion([sujeto(['Aspects', of, this, broad, and, 'ever-evolving', field, specifically, addressed, in, this, review, 'include:', the, etiology, and, significance, of]), verbo([increased]), complemento(['AR', 'expression;', the, frequency, and, role, of, 'gain-of-function', mutations, in, the, 'AR', 'gene;', the, function, of, constitutively, 'active,', truncated, forms, of, the, 'AR', termed, 'AR', variants, and, the, clinical, relevance, of, alterations, to, the, activity, and, expression, of, 'AR', coregulators])]). relacion([sujeto(['Additionally,', we, examine, the, novel, therapeutic, strategies, to]), verbo([inhibit]), complemento([these, classes, of, therapy, resistance, 'mechanisms,', with, an, emphasis, on, emerging, agents, that, act, in, a, manner, distinct, from, the, current, 'ligand-centric', approaches])]). relacion([sujeto(['Nanoemulsion']), verbo([has]), complemento([the, potential, to, overcome, several, disadvantages, in, drug, formulation])]). relacion([sujeto(['Loading', poor, 'water-soluble', drugs, in, the, appropriate, nanoemulsions]), verbo([enhances]), complemento([their, wettability, 'and/or', solubility])]). relacion([sujeto(['Associated', with, the, optimum, nanodroplets, size, or, even, combined, with, key, 'components,', the, droplets]), verbo([act]), complemento([as, a, reservoir, of, 'drugs,', enabling, nanoemulsion, to, be, multifunctional, platform, to, treat, diverse, diseases])]). relacion([sujeto(['A', number, of, important, 'advantages,', which, comprise, nanoemulsion, 'attributes,', such, as, efficient, drug]), verbo([release]), complemento([with, appropriate, 'rate,', prolonged, 'efficacy,', drug, uptake, 'control,', low, side, effects, and, drug, protection, properties, from, enzymatic, or, oxidative, 'processes,', have, been, reported, in, last, decade])]). relacion([sujeto(['These', features]), verbo([provide]), complemento([alternatives, for, designing, innovative, nanoemulsions, aiming, at, 'high-value', applications])]). relacion([sujeto(['The', role, of, photoperiod, sensitivity, '(', 'PS)', of, flowering, genes]), verbo([have]), complemento([become, well, recognized, in, 'rice,', whereas, little, attention, has, been, drawn, to, the, 'non-PS', component, of, these, 'genes,', especially, to, their, influence, on, 'gene-by-gene', interactions])]). relacion([sujeto(['Rice', populations, in, which, the, 'photoperiod-sensitive', allele, at, 'Hd1']), verbo([has]), complemento([become, insensitive, to, photoperiod, but, continued, to, affect, heading, date, '(', 'HD)', were, used, in, this, study, to, 'fine-map', a, quantitative, trait, locus, '(', 'QTL)', for, 'HD', and, analyze, its, genetic, relationship, to, 'Hd1', 'The', 'QTL', was, delimitated, to, a, 96.3, -, kb, region, on, the, distal, end, of, the, long, arm, of, chromosome, 7])]). relacion([sujeto(['Sequence', comparison, revealed, that, this, 'QTL', is, identical, to, 'Hd2', 'In', the, 'near-isogenic', line, '(', 'NIL)', populations, 'analyzed,', 'Hd1', and, 'Hd2', were, shown, to, be, photoperiod, insensitive, and]), verbo([have]), complemento([pleiotropic, effects, for, 'HD,', plant, height, and, yield, traits])]). relacion([sujeto(['The', two, genes, were]), verbo([found]), complemento([to, largely, act, additively, in, regulating, 'HD', and, yield, traits])]). relacion([sujeto(['The', results, indicate, that, 'non-PS', components, of, flowering, genes]), verbo([involved]), complemento([in, photoperiod, response, play, an, important, role, in, controlling, flowering, time, and, grain, yield, in, 'rice,', which, should, allow, breeders, to, better, manipulate, pleiotropic, genes, for, balancing, adaptability, and, 'high-yielding', accumulation])]). relacion([sujeto(['Strigolactones', are, a, recently, identified, class, of, hormone, that]), verbo([regulate]), complemento([multiple, aspects, of, plant, development])]). relacion([sujeto(['The', 'DWARF14', '(', 'D14)', 'α/β', fold, protein]), verbo([has]), complemento([been, identified, as, a, strigolactone, 'receptor,', which, can, act, through, the, 'SCF(MAX2)', ubiquitin, 'ligase,', but, the, universality, of, this, mechanism, is, not, clear])]). relacion([sujeto(['Multiple', proteins]), verbo([have]), complemento([been, suggested, as, targets, for, strigolactone, 'signalling,', including, both, direct, proteolytic, targets, of, 'SCF(MAX2),', and, downstream, targets])]). relacion([sujeto(['However,', the, relevance, and, importance, of, these, proteins, to, strigolactone, signalling, in, many, cases]), verbo([has]), complemento([not, been, fully, established])]). relacion([sujeto(['Here', we, assess, the, contribution, of, these]), verbo([targets]), complemento([to, strigolactone, signalling, in, adult, shoot, developmental, responses])]). relacion([sujeto(['We']), verbo([find]), complemento([that, all, examined, strigolactone, responses, are, regulated, by, 'SCF(MAX2)', and, 'D14,', and, not, by, other, 'D14-like', proteins])]). relacion([sujeto(['We', further, show, that, all, examined, strigolactone, responses, likely, depend, on, degradation, of, 'SMXL', proteins, in, the, 'SMXL6', 'clade,', and, not, on, the, other, proposed, proteolytic]), verbo([targets]), complemento(['BES1', or, 'DELLAs'])]). relacion([sujeto(['Taken', 'together,', our, results]), verbo([suggest]), complemento([that, in, the, adult, 'shoot,', the, dominant, mode, of, strigolactone, signalling, is, 'D14-initiated,', 'MAX2-mediated', degradation, of, 'SMXL6-related', proteins])]). relacion([sujeto(['We', confirm, that, the, 'BRANCHED1', transcription, factor, and, the, 'PIN-FORMED1', auxin, efflux, carrier, are, plausible, downstream]), verbo([targets]), complemento([of, this, pathway, in, the, regulation, of, shoot, 'branching,', and, show, that, 'BRC1', likely, acts, in, parallel, to, 'PIN1'])]). relacion([sujeto(['The', embedded, 'Fe', nanoparticles]), verbo([act]), complemento([as, glue, spots, for, preventing, interfacial, slippages, between, the, 'BISS-SWCNTs', and, the, reinforced, matrix])]). relacion([sujeto(['More', 'importantly,', the, 'BISS-SWCNTs', also]), verbo([retain]), complemento([the, high, conductivity, and, transmittance, of, the, pristine, 'SWCNTs', film])]). relacion([sujeto(['This', unique, bioinspired, material, will, be, of, great, importance, in, applications, of, multifunctional, composite, materials, and]), verbo([has]), complemento([important, implications, for, the, future, of, biomimetic, materials])]). relacion([sujeto(['Toroidal', structures, based, on, 'self-assembly', of, predesigned, building, blocks, are, 'well-established', in, the, 'literature,', but, spontaneous, 'self-organization', to, prepare, such, structures]), verbo([has]), complemento([not, been, reported, to, date])]). relacion([sujeto(['A', spontaneous, 'self-organization', of, these, nanostructures, is, then]), verbo([triggered]), complemento([to, form, stable, hybrid, microtoroids])]). relacion([sujeto(['These', microstructures, are, mechanically, robust, and, can]), verbo([act]), complemento([as, templates, to, host, metallic, nanoparticles, such, as, gold, and, silver])]). relacion([sujeto(['ZnO', is, a, prime, candidate, for, future, use, in, transparent, 'electronics;', 'however,', development, of, practical, materials]), verbo([requires]), complemento([attention, to, factors, including, control, of, its, unusual, surface, band, bending, and, surface, reactivity])]). relacion([sujeto(['In', this, 'work,', we]), verbo([have]), complemento([modified, the, 'O-polar', '(', 1, '̅),', 'Zn-polar', '(', 1, ')', ',', and, 'm-plane', '(', 101, '̅0)', surfaces, of, 'ZnO', with, phosphonic, acid, '(', 'PA)', derivatives, and, measured, the, effect, on, the, surface, band, bending, and, surface, sensitivity, to, atmospheric, oxygen])]). relacion([sujeto(['Both', 'PAs']), verbo([act]), complemento([as, surface, electron, 'donors,', increasing, the, downward, band, bending, and, the, strength, of, the, 'two-dimensional', surface, electron, accumulation, layer, on, all, of, the, 'ZnO', surfaces, investigated])]). relacion([sujeto(['On', the, 'O-polar', '(', 1, '̅)', and, 'm-plane', '(', 101, '̅0)', 'surfaces,', the, 'ODPA', modifier, produced, the, largest]), verbo([increase]), complemento([in, downward, band, bending, relative, to, the, 'hydroxyl-terminated', unmodified, surface, of, 0.55, and, 0.35, 'eV,', respectively])]). relacion([sujeto(['On', the, 'Zn-polar', '(', 1, ')', 'face,', the, 'F13OPA', modifier, gave, the, largest]), verbo([increase]), complemento(['(', by, 0.5, 'eV)', producing, a, total, downward, band, bending, of, 1.0, 'eV,', representing, '∼30%', of, the, 'ZnO', band, gap])]). relacion([sujeto(['Ultraviolet', '(', 'UV)', photoinduced, surface, wettability, and, photoconductivity, measurements, demonstrated, that, the, 'PA', modifiers, are, effective, at]), verbo([decreasing]), complemento([the, sensitivity, of, the, surface, toward, atmospheric, oxygen])]). relacion([sujeto(['Modification', with, 'PA', derivatives, produced, a, large]), verbo([increase]), complemento([in, the, persistence, of, 'UV-induced', photoconductivity, and, a, large, reduction, in, 'UV-induced', changes, in, surface, wettability])]). relacion([sujeto(['The', check, valve, consists, of, a, thermoplastic, planar, spring, and, a, soft, elastomeric, pad, that]), verbo([act]), complemento([together, to, seal, against, fluid, backflow])]). relacion([sujeto(['In', 'addition,', a, variety, of, bioactives, can, be, loaded, into, the, pores, and, subsequently]), verbo([released]), complemento([to, act, on, cells, adherent, to, the, substrate])]). relacion([sujeto(['Here,', we, construct, a, cell, microarray, on, a, plasma, polymer, coated, pSi, substrate, that, enables, the, simultaneous, culture, of, human, endothelial, cells, on, printed, immobilized, protein, 'factors,', while, a, second, soluble, growth, factor, is]), verbo([released]), complemento([from, the, same, substrate])]). relacion([sujeto(['Active', growth, factors, are]), verbo([released]), complemento([from, the, pSi, surface, over, a, period, of, several, days])]). relacion([sujeto(['Not', only, mononuclear, 'complexes,', but, also, multinuclear, complexes]), verbo([act]), complemento([as, catalysts, for, alkyne, 'cyclotrimerization,', and, their, reaction, mechanisms, have, been, intensively, investigated, toward, developing, highly, efficient, and, 'regio-', and, 'chemo-selective', catalysts])]). relacion([sujeto(['Recently,', 'small-scale', hydrogen, peroxide, '(', 'H2O2)', propulsion, mechanisms]), verbo([have]), complemento([shown, great, promise, in, delivering, pulsatile, thrust, for, such, acceleration, needs])]). relacion([sujeto(['The', 'mercapto-silanization', of, the, 'SiO2', microfibers, enables, strong, covalent, attachment, with, 'PtNPs,', and, the, resultant, 'PtNP-SiO2', fibers]), verbo([act]), complemento([as, a, 'robust,', high, surface, area, catalyst, for, 'H2O2', decomposition])]). relacion([sujeto(['Both']), verbo([enhanced]), complemento([surface, area, and, excellent, magnetization, property, were, obtained])]). relacion([sujeto([5, 'MBC600', was, superior, in, both, 'Hg(0)', adsorption, capacity, and, adsorption, rate, to, a, commercial, brominated]), verbo([activated]), complemento([carbon, '(', 'Br-AC)', used, for, mercury, removal, in, power, plants])]). relacion([sujeto(['The', 'C═O', group, could]), verbo([act]), complemento([as, act, as, electron, 'acceptors,', facilitating, the, electron, transfer, for, 'Hg(0)', oxidation])]). relacion([sujeto(['Trichinella', 'Owen,', 1835, nematodes, are]), verbo([found]), complemento([in, 'pigs,', 'horses,', and, humans, in, the, domestic, 'cycle,', and, in, many, carnivores, and, omnivores, in, the, sylvatic, 'cycle,', such, as, wild, 'boars,', red, 'foxes,', raccoon, 'dogs,', and, wolves])]). relacion([sujeto(['Carnivores', are, known, to, be]), verbo([involved]), complemento([in, the, circulation, of, 'Trichinella', nematodes, and, they, act, as, a, reservoir, in, the, sylvatic, environment])]). relacion([sujeto(['Trichinella', larvae, were]), verbo([found]), complemento([in, 10.02, '%', of, examined, samples, '(', 145, /, 1447, ')'])]). relacion([sujeto(['Our', findings, confirm, that, red, foxes, are]), verbo([involved]), complemento([in, the, maintenance, of, 'Trichinella', spp])]). relacion([sujeto(['These', programs, are]), verbo([regulated]), complemento([in, part, by, the, 'small-molecule', ligands, that, bind, 'NRs', and, modulate, their, interactions, with, transcriptional, coregulatory, factors])]). relacion([sujeto(['X-ray', crystallography, is, now, delivering, more, complete, pictures, of, how, the, multidomain, architectures, of, 'NR', 'homo-', and, heterodimers, are, physically, arranged, on, their, 'DNA', elements, and, how, ligands, and, coactivator, peptides]), verbo([act]), complemento([through, these, complexes])]). relacion([sujeto(['Prolonged', mechanical, ventilation, is]), verbo([associated]), complemento([with, a, longer, intensive, care, unit, '(', 'ICU)', length, of, stay, and, higher, mortality])]). relacion([sujeto(['Consequently,', methods, to, improve, ventilator, weaning, processes]), verbo([have]), complemento([been, sought])]). relacion([sujeto(['Growing', awareness, of, the, benefits, of, understanding, the, contextual, factors, impacting, on, effectiveness]), verbo([has]), complemento([encouraged, the, integration, of, qualitative, evidence, syntheses, with, effectiveness, 'reviews,', which, has, delivered, important, insights, into, the, reasons, underpinning, '(', 'differential)', effectiveness, of, healthcare, interventions])]). relacion([sujeto(['To', use, the, integrated, body, of, evidence, to]), verbo([suggest]), complemento([the, circumstances, in, which, weaning, protocols, are, most, likely, to, be, used])]). relacion([sujeto(['We', also, contacted, authors, of, the, trials, included, in, the, effectiveness, reviews, as, well, as, of, studies, '(', 'potentially)', included, in, the, qualitative, 'synthesis,', conducted, citation, searches, of, the, publications]), verbo([reporting]), complemento([these, 'studies,', and, contacted, content, experts])]). relacion([sujeto(['We', reran, the, search, on, 3, rd, 'July', 2016, and]), verbo([found]), complemento([three, 'studies,', which, are, awaiting, classification])]). relacion([sujeto(['We', included, qualitative, studies, that, 'described:', the, circumstances, in, which, protocols, are, 'designed,', implemented, or, 'used,', or, 'both,', and, the, views, and, experiences, of, healthcare, professionals, either]), verbo([involved]), complemento([in, the, 'design,', implementation, or, use, of, weaning, protocols, or, involved, in, the, weaning, of, 'critically-ill', adults, and, children, from, mechanical, ventilation, not, using, protocols])]). relacion([sujeto(['We', included, studies, 'that:', reflected, on, any, aspect, of, the, use, of, 'protocols,', explored, contextual, factors, relevant, to, the, 'development,', implementation, or, use, of, weaning, 'protocols,', and]), verbo([reported]), complemento([contextual, phenomena, and, outcomes, identified, as, relevant, to, the, effectiveness, of, protocolized, weaning, from, mechanical, ventilation])]). relacion([sujeto(['We', included, 11, studies, in, our, 'synthesis,']), verbo([involving]), complemento([267, participants, '(', one, study, did, not, report, the, number, of, 'participants)'])]). relacion([sujeto(['Our', synthesis, produced, nine, analytical, 'themes,', which]), verbo([report]), complemento([potential, barriers, and, facilitators, to, the, use, of, protocols])]). relacion([sujeto(['The', themes, 'are:', the, need, for, continual, staff, training, and, 'development;', clinical, experience, as, this]), verbo([promotes]), complemento([felt, and, perceived, competence, and, confidence, to, 'wean;', the, vulnerability, of, weaning, to, disparate, interprofessional, 'working;', an, understanding, of, protocols, as, militating, against, a, necessary, proactivity, in, clinical, 'practice;', perceived, nursing, scope, of, practice, and, professional, 'risk;', 'ICU', structure, and, processes, of, 'care;', the, ability, of, protocols, to, act, as, a, prompt, for, shared, care, and, consistency, in, weaning, 'practice;', maximizing, the, use, of, protocols, through, visibility, and, ease, of, 'implementation;', and, the, ability, of, protocols, to, act, as, a, framework, for, communication, with, parents])]). relacion([sujeto(['In', terms, of, protocol, 'development,', comprehensive, interprofessional, input, will, help, to]), verbo([ensure]), complemento(['broad-based', understanding, and, a, sense, of, '\'', 'ownership\''])]). relacion([sujeto(['In', order, to, maximize, relevance, and, 'acceptability,', protocols, should, be, designed, with, the, patient, profile, and, requirements, of, the]), verbo([target]), complemento(['ICU', in, mind])]). relacion([sujeto(['Surface', 'nanobubbles,', which, are, nanoscopic, or, microscopic, gaseous, domains, forming, at, the, 'solid/liquid', 'interface,']), verbo([have]), complemento([a, strong, impact, on, the, interface, by, changing, the, 'two-phase', contact, to, a, 'three-phase', contact])]). relacion([sujeto(['However,', there, are, still, disputes, in, the, theoretical, studies, as, to, whether, the, nanobubbles, can]), verbo([increase]), complemento([the, slip, length, effectively])]). relacion([sujeto(['Our', experimental, results]), verbo([reveal]), complemento([an, increase, from, 8, to, 512, nm, in, slip, length, by, increasing, the, surface, coverage, of, nanobubbles, from, 1.7, to, 50.8, '%', and, by, decreasing, the, contact, angle, of, nanobubbles, from, 42.8, to, 16.6, °])]). relacion([sujeto(['Our', results, indicate, that, nanobubbles, could, always]), verbo([act]), complemento([as, a, lubricant, and, significantly, increase, the, slip, length])]). relacion([sujeto(['They', are, transported, to, their, site, of, action, as, 'blood-borne', endocrine, hormones, but, can, also, be, produced, within, tissues, to]), verbo([act]), complemento([in, intracrine, and, paracrine, fashions])]). relacion([sujeto(['Here,', derivatization, with, 'Girard', 'T', reagent, was, used, to, 'charge-tag', testosterone, and, 5, 'α-dihydrotestosterone', allowing, direct, detection, of, these, steroids, in, mouse, 'testes,', in, both, basal, and, maximally]), verbo([stimulated]), complemento(['states,', and, in, rat, prostate])]). relacion([sujeto(['Structural', confirmation, was, achieved, by, collision]), verbo([induced]), complemento([fragmentation, following, liquid, extraction, surface, analysis, and, electrospray, ionization])]). relacion([sujeto(['What', is, the, central, question, of, this, 'study?', 'Do', group, 'III', and, 'IV', muscle, afferents]), verbo([act]), complemento([at, the, spinal, or, cortical, level, to, affect, the, ability, of, the, central, nervous, system, to, drive, quadriceps, muscles, during, fatiguing, 'exercise?', 'What', is, the, main, finding, and, its, 'importance?', 'The', excitability, of, the, motoneurone, pool, of, vastus, lateralis, was, unchanged, by, feedback, from, group, 'III', and, 'IV', muscle, afferents])]). relacion([sujeto(['In', upper, limb, 'muscles,', changes, in, afferent, 'feedback,', motoneurone, 'excitability,', and, motor, cortical, output, can, contribute, to, failure, of, the, central, nervous, system, to]), verbo([recruit]), complemento([muscles, fully, during, fatigue])]). relacion([sujeto(['We', assessed, the, corticospinal, pathway, to, vastus, lateralis, during, fatiguing, sustained, maximal, voluntary, contractions, '(', 'MVCs)', of, the, knee, extensors, and, during, firing, of, 'fatigue-sensitive', group, 'III/IV', muscle, afferents]), verbo([maintained]), complemento([by, postexercise, ischaemia, after, fatiguing, 'MVCs', of, the, knee, extensors, 'and,', 'separately,', the, flexors])]). relacion([sujeto(['During', the, 2, -, min, extensor, 'contraction,', the, size, of, vastus, lateralis, 'MEPs', normalized, to, the, maximal, 'M-wave']), verbo([increased]), complemento(['(', 'P < 0'])]). relacion([sujeto(['After', the, 2, -, min, 'MVC,']), verbo([maintained]), complemento([firing, of, group, 'III/IV', muscle, afferents, had, no, effect, on, vastus, lateralis, 'MEPs', or, 'TMEPs', '(', 'P = 0'])]). relacion([sujeto(['Likewise,', after, the, 2, -, min, knee, flexor, 'MVC,']), verbo([maintained]), complemento([firing, of, these, afferents, showed, no, effect, on, vastus, 'lateralis MEPs', or, 'TMEPs', '(', 'P = 0'])]). relacion([sujeto(['Yeasts']), verbo([have]), complemento([sophisticated, signaling, pathways, for, sensing, 'glucose,', their, preferred, carbon, 'source,', to, regulate, its, uptake, and, metabolism])]). relacion([sujeto(['One', of, these, is, the, 'sensor/receptor-repressor', '(', 'SRR)', 'pathway,', which, detects, extracellular, glucose, and, transmits, an, intracellular, signal, that]), verbo([induces]), complemento([expression, of, 'HXT', genes])]). relacion([sujeto(['Our', model, of, the, 'SRR', pathway, had, the, 'Ycks', functioning, downstream, of, the, glucose, 'sensors,', transmitting, the, signal, from, the, sensors, to, the, 'Mth1', and, 'Std1', corepressors, that, are]), verbo([required]), complemento([for, repression, of, 'HXT', gene, expression])]). relacion([sujeto(['However,', we]), verbo([found]), complemento([that, overexpression, of, 'Yck1', fails, to, restore, glucose, signaling, in, a, glucose, sensor, mutant])]). relacion([sujeto(['Conversely,', overexpression, of, a, glucose, sensor]), verbo([suppresses]), complemento([the, signaling, defect, of, a, yck, mutant])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, the, 'Ycks', act, upstream, or, at, the, level, of, the, glucose, sensors])]). relacion([sujeto(['Indeed,', we]), verbo([found]), complemento([that, the, glucose, sensor, 'Rgt2', is, phosphorylated, on, 'Yck', consensus, sites, in, its, 'C-terminal', tail, in, a, 'Yck-dependent', manner, and, that, this, phosphorylation, is, required, for, corepressor, binding, and, ultimately, 'HXT', expression])]). relacion([sujeto(['This']), verbo([leads]), complemento([to, a, revised, model, of, the, 'SRR', pathway, in, which, the, 'Ycks', prime, a, site, on, the, cytoplasmic, tails, of, the, glucose, sensors, to, promote, binding, of, the, corepressors])]). relacion([sujeto(['The', molecular, programme, underlying, tendon, development]), verbo([has]), complemento([not, been, fully, identified])]). relacion([sujeto(['Limb', tendons, initiate, their, development, independently, of, 'muscles;', 'however,', muscles, are]), verbo([required]), complemento([for, further, tendon, differentiation])]). relacion([sujeto(['We', show, that, both, 'FGF/ERK', 'MAPK', and, 'TGFβ/SMAD2/3', signalling, pathways, are]), verbo([required]), complemento([and, sufficient, for, 'SCX', expression, in, chick, undifferentiated, limb, 'cells,', whereas, the, 'FGF/ERK', 'MAPK', pathway, inhibits, 'Scx', expression, in, mouse, undifferentiated, limb, mesodermal, cells])]). relacion([sujeto(['During', 'differentiation,', muscle, contraction, is]), verbo([required]), complemento([to, maintain, 'SCX,', 'TNMD', and, 'THBS2', expression, in, chick, limbs])]). relacion([sujeto(['The', activities, of, 'FGF/ERK', 'MAPK', and, 'TGFβ/SMAD2/3', signalling, pathways, are]), verbo([decreased]), complemento([in, tendons, under, immobilisation, conditions])]). relacion([sujeto(['Application', of, 'FGF4', or, 'TGFβ2', ligands]), verbo([prevents]), complemento(['SCX', downregulation, in, immobilised, limbs])]). relacion([sujeto(['TGFβ2', but, not, 'FGF4']), verbo([prevent]), complemento(['TNMD', and, 'THBS2', downregulation, under, immobilisation, conditions])]). relacion([sujeto(['Independently', of, each, 'other,', both, 'FGF', and, 'TGFβ']), verbo([promote]), complemento([tendon, commitment, of, limb, mesodermal, cells, and, act, downstream, of, mechanical, forces, to, regulate, tendon, differentiation, during, chick, limb, development])]). relacion([sujeto(['Vascular', endothelial, growth, factor, 'C', '(', 'Vegfc)']), verbo([activates]), complemento([its, 'receptor,', 'Flt4,', to, induce, lymphatic, development])]). relacion([sujeto(['However,', the, signals, that]), verbo([act]), complemento([downstream, of, 'Flt4', in, this, context, in, vivo, remain, unclear])]). relacion([sujeto(['Deletion', of, 'Y1226/7']), verbo([prevented]), complemento(['ERK', phosphorylation, in, lymphatic, 'progenitors,', and, 'ERK', inhibition, blocked, trunk, lymphatic, sprouting, and, differentiation])]). relacion([sujeto(['In', 2002, ',', the, 'Belgian', 'Act', on, 'Euthanasia', came, into, 'effect,']), verbo([regulating]), complemento([the, intentional, ending, of, life, by, a, physician, at, the, 'patient\'s', explicit, request])]). relacion([sujeto(['We', undertook, this, study, to, describe, trends, in, officially]), verbo([reported]), complemento([euthanasia, cases, in, 'Belgium', with, regard, to, 'patients\'', sociodemographic, and, clinical, 'profiles,', as, well, as, 'decision-making', and, performance, characteristics])]). relacion([sujeto(['We', used, the, database, of, all, euthanasia, cases]), verbo([reported]), complemento([to, the, 'Federal', 'Control', and, 'Evaluation', 'Committee', on, 'Euthanasia', in, 'Belgium', between, 'Jan'])]). relacion([sujeto(['We', also, compared, and, analyzed, trends, for, cases]), verbo([reported]), complemento([in, 'Dutch', and, in, 'French'])]). relacion([sujeto(['The', number, of]), verbo([reported]), complemento([euthanasia, cases, increased, every, 'year,', from, 235, '(', 0.2, '%', of, all, 'deaths)', in, 2003, to, 1807, '(', 1.7, '%', of, all, 'deaths)', in, 2013])]). relacion([sujeto(['The', rate, of, euthanasia]), verbo([increased]), complemento([significantly, among, those, aged, 80, years, or, 'older,', those, who, died, in, a, nursing, 'home,', those, with, a, disease, other, than, cancer, and, those, not, expected, to, die, in, the, near, future, '(', p, &, 'lt;', 0.001, for, all, 'increases)'])]). relacion([sujeto(['Among', cases]), verbo([reported]), complemento([in, 'Dutch,', the, proportion, in, which, the, person, was, expected, to, die, in, the, foreseeable, future, decreased, from, 93.9, '%', in, 2003, to, 84.1, '%', in, 2013, ',', and, palliative, care, teams, were, increasingly, consulted, about, the, euthanasia, request, '(', from, 34.0, '%', in, 2003, to, 42.6, '%', in, 2013, ')'])]). relacion([sujeto(['These', trends, were, not, significant, for, cases]), verbo([reported]), complemento([in, 'French'])]). relacion([sujeto(['Since', legalization, of, euthanasia, in, 'Belgium,', the, number, of]), verbo([reported]), complemento([cases, has, increased, each, year])]). relacion([sujeto(['Given', the]), verbo([increases]), complemento([observed, among, 'non-terminally', ill, and, older, 'patients,', this, analysis, shows, the, importance, of, detailed, monitoring, of, developments, in, euthanasia, practice])]). relacion([sujeto(['This', is, the, first, analysis, to, address, the, representation, of, the]), verbo([act]), complemento([of, donation, from, the, viewpoint, of, both, donor, and, recipient, families, through, interrogation, of, archived, correspondence, 'data,', using, linguistic, techniques])]). relacion([sujeto(['This', programmed, type, 'I>0', switch, is, controlled, by, 'Notch', 'signaling,']), verbo([triggered]), complemento([at, a, distinct, point, of, lineage, progression, in, each, neuroblast])]). relacion([sujeto(['Here,', we]), verbo([find]), complemento([that, seq, mutants, fail, to, execute, the, type, 'I>0', daughter, proliferation, switch, and, also, display, increased, neuroblast, proliferation])]). relacion([sujeto(['Genetic', interaction, studies]), verbo([reveal]), complemento([that, seq, interacts, with, the, 'Notch', 'pathway,', and, seq, furthermore, affects, expression, of, a, 'Notch', pathway, reporter])]). relacion([sujeto(['These', findings]), verbo([suggest]), complemento([that, seq, may, act, as, a, 'context-dependent', regulator, of, 'Notch', 'signaling,', and, underscore, the, growing, connection, between, 'Seq,', 'Ttk,', the, 'PRDM', family, and, 'Notch', signaling])]). relacion([sujeto(['Here,', we, examine, the]), verbo([act]), complemento([of, gift, giving, and, receiving, within, a, 'Ugandan', maternity, care, 'setting,', describing, the, connections, between, these, material, objects, and, social, relations])]). relacion([sujeto(['A', study, investigating, the, social, organisation, of, maternity, care, in, 'post-conflict', northern, 'Uganda']), verbo([found]), complemento([that, 'gift-giving', to, new, mothers, functioned, to, create, a, material, and, discursive, context, wherein, 'women\'s', desire, to, access, these, goods, was, leveraged, to, create, an, incentive, to, attend, formal, maternity, care, during, pregnancy, and, for, delivery])]). relacion([sujeto(['Graphene', oxide, '(', 'GO)', is, one, of, the, most, appealing, bidimensional, materials, able, to]), verbo([interact]), complemento(['non-covalently', with, achiral, molecules, and, to, act, as, chiral, inducers])]). relacion([sujeto(['Autophagy', plays, a, critical, role, in]), verbo([maintaining]), complemento([cell, homeostasis, in, response, to, various, stressors, through, protein, conjugation, and, activation, of, 'lysosome-dependent', degradation])]). relacion([sujeto(['MAP1LC3B/LC3B', '(', 'microtubule-']), verbo([associated]), complemento([protein, 1, light, chain, 3, 'β)', is, conjugated, with, phosphatidylethanolamine, '(', 'PE)', in, the, membranes, and, regulates, initiation, of, autophagy, through, interaction, with, many, 'autophagy-related', proteins, possessing, an, 'LC3-interacting', region, '(', 'LIR)', 'motif,', which, is, composed, of, 2, hydrophobic, amino, acids, '(', tryptophan, and, 'leucine)', separated, by, 2, 'non-conserved', amino, acids, '(', 'WXXL)'])]). relacion([sujeto(['In', this, 'study,', we, identified, a, new, putative, 'LIR', motif, in, 'PEBP1/RKIP', '(', phosphatidylethanolamine]), verbo([binding]), complemento([protein, 1, ')', that, was, originally, isolated, as, a, 'PE-binding', protein, and, also, a, cellular, inhibitor, of, 'MAPK/ERK', signaling])]). relacion([sujeto(['PEBP1', was, specifically]), verbo([bound]), complemento([to, 'PE-unconjugated', 'LC3', in, 'cells,', and, mutation, '(', 'WXXL', mutated, to, 'AXXA)', of, this, 'LIR', motif, disrupted, its, interaction, with, 'LC3', proteins])]). relacion([sujeto(['Interestingly,', overexpression, of, 'PEBP1', significantly]), verbo([inhibited]), complemento(['starvation-induced', autophagy, by, activating, the, 'AKT', and, 'MTORC1', '(', mechanistic, target, of, rapamycin, '[', 'serine/threonine', 'kinase]', complex, 1, ')', signaling, pathway, and, consequently, suppressing, the, 'ULK1', '(', 'unc-51', like, autophagy, activating, kinase, 1, ')', activity])]). relacion([sujeto(['In', 'contrast,', ablation, of, 'PEBP1', expression, dramatically]), verbo([promoted]), complemento([the, autophagic, process, under, starvation, conditions])]). relacion([sujeto(['Furthermore,', 'PEBP1', lacking, the, 'LIR', motif, highly]), verbo([stimulated]), complemento(['starvation-induced', autophagy, through, the, 'AKT-MTORC1-dependent', pathway])]). relacion([sujeto(['PEBP1', phosphorylation, at, 'Ser153']), verbo([caused]), complemento([dissociation, of, 'LC3', from, the, 'PEBP1-LC3', complex, for, autophagy, induction])]). relacion([sujeto(['PEBP1-dependent', suppression, of, autophagy, was, not]), verbo([associated]), complemento([with, the, 'MAPK', pathway])]). relacion([sujeto(['These', findings]), verbo([suggest]), complemento([that, 'PEBP1', can, act, as, a, negative, mediator, in, autophagy, through, stimulation, of, the, 'AKT-MTORC1', pathway, and, direct, interaction, with, 'LC3'])]). relacion([sujeto(['Poly(ADP-ribose)', polymerases, '(', 'PARPs/ARTDs)', use, nicotinamide, adenine, dinucleotide, '(', 'NAD(+))', to, catalyse, the, synthesis, of, a, long, branched, 'poly(ADP-ribose)', polymer, '(', 'PAR)', attached, to, the, acceptor, amino, acid, residues, of]), verbo([nuclear]), complemento([proteins])]). relacion([sujeto(['PARPs']), verbo([act]), complemento([on, 'single-', and, 'double-stranded', 'DNA', breaks, by, recruiting, 'DNA', repair, factors])]). relacion([sujeto(['Here,', in, in, vitro, biochemical, 'experiments,', we]), verbo([found]), complemento([that, the, mammalian, 'PARP1', and, 'PARP2', proteins, can, directly, 'ADP-ribosylate', the, termini, of, 'DNA', oligonucleotides])]). relacion([sujeto(['Biochemical', and, mass, spectrometry, analyses, of, the, adducts]), verbo([suggested]), complemento([that, 'PARPs', utilise, 'DNA', termini, as, an, alternative, to, 2, '\'', -, hydroxyl, of, 'ADP-ribose', and, protein, acceptor, residues, to, catalyse, 'PAR', chain, initiation, either, via, the, 2, '\'', ',', 1, '″-O-glycosidic', 'ribose-ribose', bond, or, via, phosphodiester, bond, formation, between, 'C1\'', of, 'ADP-ribose', and, the, phosphate, of, a, terminal, deoxyribonucleotide])]). relacion([sujeto(['This', new, type, of, 'post-replicative', modification, of, 'DNA']), verbo([provides]), complemento([novel, insights, into, the, molecular, mechanisms, underlying, biological, phenomena, of, 'ADP-ribosylation', mediated, by, 'PARPs'])]). relacion([sujeto(['Sexual', signalling, is, predicted, to, shape, the, evolution, of, 'sex-specific', 'ornamentation,', and, establishing, the, costs, and, benefits, of, ornamentation, and, the, information, that, ornamentation]), verbo([provides]), complemento([to, receivers, is, necessary, to, evaluating, this, adaptive, function])]). relacion([sujeto(['We', hypothesized, that, greater, ornamentation, would, improve, 'territory-holding', success, by]), verbo([decreasing]), complemento([aggression, that, males, receive, from, territorial, 'rivals,', but, that, more, ornamented, males, may, have, shorter, lifespans])]). relacion([sujeto(['Using', 'mark-recapture', field, 'observations,', we]), verbo([found]), complemento([that, more, ornamented, males, had, greater, 'territory-holding', success, and, that, viability, selection, did, not, act, on, wing, melanization])]). relacion([sujeto(['We', then, compared, the, aggression, of, territorial, rivals, to, decoy, males, before, and, after, experimentally, augmenting, wing, 'melanization,']), verbo([finding]), complemento([that, males, significantly, reduced, aggression, following, the, manipulation])]). relacion([sujeto(['We', observed, a, positive, relationship, between, ornamentation, and, the, likelihood, of, winning, territorial, 'disputes,']), verbo([suggesting]), complemento([that, wing, melanization, provides, information, about, fighting, ability, to, rivals])]). relacion([sujeto(['We', also]), verbo([found]), complemento([a, positive, relationship, between, 'melanin-based', immune, defence, and, 'ornamentation,', supporting, a, link, between, the, signal, and, condition])]). relacion([sujeto(['We', conclude, that, wing, melanization, is, a, 'condition-related', signal, of, fighting, ability, and]), verbo([suggest]), complemento([that, this, may, be, a, common, mechanism, promoting, the, evolution, of, melanin, ornamentation])]). relacion([sujeto(['Eukaryotic', gene, expression]), verbo([requires]), complemento([that, 'RNA', 'Polymerase', 'II', '(', 'RNAP', 'II)', gain, access, to, 'DNA', in, the, context, of, chromatin])]). relacion([sujeto(['The', 'C-terminal', domain, '(', 'CTD)', of, 'RNAP', 'II']), verbo([recruits]), complemento([chromatin, modifying, enzymes, to, 'promoters,', allowing, for, transcription, initiation, or, repression])]). relacion([sujeto(['However,', the, readable, code, for]), verbo([recruiting]), complemento([such, factors, is, still, not, fully, defined, and, how, 'CTD', modifications, affect, related, families, of, genes, or, regional, gene, expression, is, not, well, understood])]). relacion([sujeto(['The', data, further, indicate, that, 'H3K9me', and, expression, status, are, not, fully, 'correlated,', suggestive, of, 'CTD-dependent', subtelomeric, repression, mechansims, that]), verbo([act]), complemento([independently, of, 'H3K9me', levels])]). relacion([sujeto(['Smooth', muscle, cell, '(', 'SMC)', phenotypic, conversion, from, a, contractile, to, a, migratory, phenotype, is, proposed, to, underlie, cardiovascular, disease, but, its, contribution, to, vascular, remodelling, and, even, its, existence]), verbo([have]), complemento([recently, been, questioned])]). relacion([sujeto(['This', study]), verbo([provides]), complemento([a, direct, demonstration, of, the, transition, of, fully, contractile, 'SMCs', to, a, 'non-contractile,', migratory, phenotype, with, phagocytic, capacity, that, may, act, as, a, 'macrophage-like', cell])]). relacion([sujeto(['Recently,', these, views]), verbo([have]), complemento([been, 'challenged,', with, reports, that, 'SMC', phenotypic, modulation, may, not, occur, during, vascular, remodelling, and, that, plaque, macrophages, may, not, be, of, haematopoietic, origin])]). relacion([sujeto(['However,', migratory, 'SMCs', did, not, uptake, acetylated, 'low-density', lipoprotein, or]), verbo([express]), complemento([the, classic, macrophage, marker, 'CD68'])]). relacion([sujeto(['Resident', 'SMCs', may]), verbo([provide]), complemento([a, potential, source, of, macrophages, in, vascular, remodelling])]). relacion([sujeto(['It']), verbo([has]), complemento([been, shown, that, the, stabilization, of, nanobubbles, is, realized, by, the, adsorption, of, chaotropic, anions, at, the, 'interface,', whereas, the, influence, of, cosmotropic, cations, is, weak])]). relacion([sujeto(['With']), verbo([increasing]), complemento(['temperature,', it, should, be, accounted, for, by, blurring, the, interface, due, to, thermal, fluctuations])]). relacion([sujeto(['It', turned, out, that, in, the, case, of, liquid, samples, being, kept, in, hermetically, sealed, 'ampules,', where, the, phase, equilibrium, at, the, 'liquid-gas', interface, is, fulfilled, for, any, 'temperature,', the, volume, number, density, of, nanobubbles]), verbo([decreases]), complemento([with, increasing, temperature, and, this, decrease, is, irreversible])]). relacion([sujeto([β2, -, 'Adrenoreceptor', agonists, that]), verbo([act]), complemento([via, cAMP, can, reduce, uterine, contractions, to, delay, preterm, 'labour,', but, their, ability, to, repress, uterine, contractions, lasts, '≤ 48 h', and, their, use, does, not, improve, neonatal, outcomes])]). relacion([sujeto(['Previous', research]), verbo([has]), complemento([suggested, that, cAMP, inhibits, myometrial, contractions, via, protein, kinase, 'A', '(', 'PKA)', 'activation,', but, this, has, yet, to, be, demonstrated, with, 'PKA-specific', agonists])]). relacion([sujeto(['We', investigated, the, role, of, 'PKA', in]), verbo([mediating]), complemento(['cAMP-induced', human, myometrial, 'relaxation,', and, the, impact, of, prolonged, cAMP, elevation, on, myometrial, contractility])]). relacion([sujeto(['Our', findings]), verbo([suggest]), complemento([that, 'PKA', is, not, the, sole, mediator, of, 'cAMP-induced', myometrial, relaxation, and, that, prolonged, prophylactic, elevation, of, cAMP, alone, is, unlikely, to, prevent, preterm, labour, '(', 'PTL)'])]). relacion([sujeto(['Acute', cAMP, elevation]), verbo([inhibits]), complemento([myometrial, 'contractility,', but, the, mechanisms, responsible, are, not, fully, elucidated, and, the, 'long-term', effects, are, uncertain])]). relacion([sujeto(['In', the, present, 'study,', we, tested, the, hypotheses, that, 'PKA', activity, is, necessary, for, 'cAMP-induced', myometrial, 'relaxation,', and, that, prolonged, cAMP, elevation, can]), verbo([prevent]), complemento([myometrial, contractions])]). relacion([sujeto(['Acute', '(', 1, &, 'nbsp;h)', application, of, cAMP, agonists]), verbo([promoted]), complemento([myometrial, 'relaxation,', but, this, was, weakly, related, to, 'PKA', activation])]). relacion([sujeto(['A', 'PKA-specific', 'activator,', 6, -, 'Bnz-cAMP,']), verbo([increased]), complemento(['PKA', activity, '(', 6.8, &, 'nbsp;± 2'])]). relacion([sujeto([313, ')', without]), verbo([inducing]), complemento([myometrial, relaxation])]). relacion([sujeto([43, ')', ;, this, was]), verbo([associated]), complemento([with, changes, to, 'calponin,', cofilin, and, 'HSP20', 'phosphorylated/total', protein, levels])]). relacion([sujeto(['Oxytocin-induced', contractions, were, unaffected, by, 'pre-incubation', with, cAMP, agonists, despite, treatments, being, able, to]), verbo([enhance]), complemento(['PKA', activity, and, 'HSP20', phosphorylation])]). relacion([sujeto(['These', data]), verbo([suggest]), complemento([that, 'cAMP-induced', myometrial, relaxation, is, not, solely, dependent, on, 'PKA', activity, and, the, ability, of, cAMP, agonists, to, repress, myometrial, contractility, is, lost, with, prolonged, exposure])]). relacion([sujeto(['We', conclude, that, cAMP, agonist, treatment, alone, may, not]), verbo([prevent]), complemento([preterm, labour])]). relacion([sujeto(['Tubular', transport]), verbo([regulates]), complemento([body, homeostasis, and, the, associated, transport, work, is, a, primary, determinant, of, the, 'kidneys\'', energy, needs])]). relacion([sujeto(['In', 'particular,', proximal, tubules, and, thick, ascending, limbs]), verbo([have]), complemento([been, proposed, to, act, as, 'sensors,', effectors, and, injury, recipients, of, 'AKI', stimuli])]). relacion([sujeto(['Surprisingly', little, attention]), verbo([has]), complemento([been, given, to, aspects, of, tubular, transport, function, in, 'AKI', and, the, relevance, for, kidney, recovery])]). relacion([sujeto(['This', review, aims, to, outline, changes, in, tubular, transport, function, in, 'AKI,', discusses, their, potential, consequences, and, relevance, for, the, diagnosis, and, prognosis, of, 'AKI', and, its, 'recovery,', including, changes, in, 'GFR,', and, poses, the, question, whether, tubular, transport]), verbo([provides]), complemento([an, opportunity, for, intervention, to, rest, the, tubular, 'system,', which, may, have, consequences, for, the, progression, to, 'CKD'])]). relacion([sujeto(['These', aqueous, solutions, containing, bubbles]), verbo([have]), complemento([been, evaluated, for, cleaning, efficacy, in, the, removal, of, model, contaminants, bovine, serum, albumin, and, lysozyme, from, surfaces, and, in, the, prevention, of, the, fouling, of, surfaces, by, these, same, proteins])]). relacion([sujeto(['It', is, shown, that, nanobubbles, can]), verbo([prevent]), complemento([the, fouling, of, surfaces, and, that, they, can, also, clean, already, fouled, surfaces])]). relacion([sujeto(['It', is, also, argued, that, in, practical, applications, where, cleaning, is, carried, out, rapidly, using, a, high, degree, of, mechanical, agitation, the, role, of, cleaning, agents, is, not, primarily, in, assisting, the, removal, of, soil, but, in, suspending, the, soil, that, is, removed, by, mechanical, action, and]), verbo([preventing]), complemento([it, from, redepositing, onto, surfaces])]). relacion([sujeto(['What', is, the, topic, of, this, 'review?', 'The', review, discusses, how, in, atherosclerotic, 'plaques,', a, combination, of, inflammatory, mediators, together, with]), verbo([loss]), complemento([of, anti, inflammatory, factors, is, most, likely, to, be, responsible, for, the, excess, of, 'MMP', over, 'TIMP', expression, that, causes, plaque, rupture, and, myocardial, infarction])]). relacion([sujeto(['Inflammatory', cytokines]), verbo([act]), complemento([through, distinct, '(', albeit, 'overlapping)', signalling, pathways, to, elicit, different, patterns, of, 'MMP', and, 'TIMP', expression])]). relacion([sujeto(['In', human, 'monocytes,', 'prostaglandin E2', '(', 'PGE2', ')']), verbo([stimulates]), complemento(['MMP', 'production,', and, inflammatory, mediators, such, as, tumour, necrosis, 'factor α,', 'interleukin-1', and, 'Toll-like', receptor, ligands, can, act, either, through, or, independently, of, 'PGE2'])]). relacion([sujeto(['Differentiation', of, human, monocytes, to, 'non-foamy', macrophages]), verbo([increases]), complemento([constitutive, expression, of, 'MMP-7,', -, 8, ',', -, 9, ',', -, 14, and, -, 19, and, tissue, inhibitor, of, 'MMP', '(', 'TIMP)-1', to, -, 3, through, 'unknown,', 'PGE2', -, independent, mechanisms])]). relacion([sujeto(['Human', macrophages]), verbo([express]), complemento([more, 'MMP-1,', -, 7, and, -, 9, and, 'TIMP-3', and, less, 'MMP-12', and, -, 13, than, mouse, macrophages])]). relacion([sujeto(['Inflammatory', mediators, working, through, activator, 'protein-1', and]), verbo([nuclear]), complemento(['factor-κB', transcription, factor, pathways, upregulate, 'MMP-1,', -, 3, ',', -, 10, ',', -, 12, and, -, 14, in, human, macrophages, '(', 'MMP-9,', -, 12, and, -, 13, in, 'mice),', and, studies, with, plaque, tissue, sections, and, isolated, foam, cells, confirm, this, conclusion, in, vivo])]). relacion([sujeto(['Alternative', activation, with, 'interleukin-4', markedly]), verbo([stimulates]), complemento([the, expression, of, only, 'MMP-12', in, humans, and, 'MMP-19', in, mice])]). relacion([sujeto(['The', 'anti-inflammatory', cytokines, 'interleukin-10', and, transforming, growth, 'factor-β']), verbo([decrease]), complemento([production, of, several, 'MMPs'])]). relacion([sujeto(['Epigenetic', upregulation, of, 'MMP-14', during, foam, cell, formation, or, by, 'granulocyte-macrophage', 'colony-stimulating', factor, occurs, by]), verbo([decreasing]), complemento(['miRNA-24'])]). relacion([sujeto(['A', '\'', perfect, 'storm\'']), verbo([caused]), complemento([by, a, combination, of, these, mechanisms, is, most, likely, to, promote, 'MMP-mediated', macrophage, 'invasion,', tissue, destruction, and, atherosclerotic, plaque, rupture])]). relacion([sujeto(['Microbeads', containing, only, fresh, 'BMMC', or, only, cultured, 'MSC']), verbo([maintained]), complemento([in, osteogenic, medium, resulted, in, more, bone, formation, than, their, counterparts, cultured, in, growth, medium])]). relacion([sujeto(['These', data]), verbo([suggest]), complemento([that, components, of, the, 'BMMC', fraction, can, act, synergistically, with, predifferentiated, 'MSC', to, potentiate, ectopic, bone, formation])]). relacion([sujeto(['The', microbead, system, may]), verbo([have]), complemento([utility, in, delivering, desired, cell, populations, in, bone, regeneration, applications])]). relacion([sujeto(['A', literature, review, aimed, at]), verbo([finding]), complemento([evidence, on, outpatient, prescription, drug, costs, was, performed, using, the, following, 'sources:', 'PubMed,', governmental, 'agencies,', news, 'websites,', the, 'Academy', of, 'Managed', 'Care', 'Pharmacy', '(', 'AMCP)', 'website,', and, 'Google', 'Scholar'])]). relacion([sujeto(['The', 'Drug', 'Cost', 'Focus', 'Group', '(', 'DCFG)', was, convened, to, supplement, the, literature, 'review;', the, 'DCFG']), verbo([provided]), complemento([their, expertise, on, 'US', drug, costs, and, emerging, issues, affecting, drug, costs])]). relacion([sujeto(['ACA', legislation]), verbo([increased]), complemento([drug, rebates, for, manufacturers, participating, in, the, 'Medicaid', 'Drug', 'Rebate', 'Program'])]). relacion([sujeto(['Evidence']), verbo([suggests]), complemento([that, reimbursement, methods, in, the, public, market, are, varied])]). relacion([sujeto(['The', shortage, of, primary, care, providers, and, the, provisions, of, the, 'Affordable', 'Care', 'Act', '(', 'ACA)']), verbo([have]), complemento([spurred, discussion, about, expanding, the, 'number,', scope, of, practice, '(', 'SOP),', and, independence, of, primary, care, nurse, practitioners, '(', 'NPs)'])]). relacion([sujeto(['The', theme, &, 'quot;knowing', your, 'limits"', was, important, to, both, 'NPs', and, physicians, regarding, 'NP', 'independence,', and]), verbo([has]), complemento([not, been, described, previously, in, the, literature])]). relacion([sujeto(['Despite', vast, improvements, that]), verbo([have]), complemento([been, made, in, the, treatment, of, children, with, acute, lymphoblastic, leukemia, '(', 'ALL),', the, majority, of, infant, 'ALL', patients, '(', '~80 %,', &, 'lt;', 1, &, 'nbsp;year', of, 'age)', that, carry, a, chromosomal, translocation, involving, the, mixed, lineage, leukemia, '(', 'MLL)', gene, shows, a, poor, response, to, chemotherapeutic, 'drugs,', especially, glucocorticoids, '(', 'GCs),', which, are, essential, components, of, all, current, treatment, regimens])]). relacion([sujeto(['Although', addressed, in, several, 'studies,', the, 'mechanism(s)', underlying, this, phenomenon]), verbo([have]), complemento([remained, largely, unknown])]). relacion([sujeto(['Here,', we, aimed, at, studying, 'GC', resistance, in, 'MLL-rearranged', infant, 'ALL', patients, by, inferring, an]), verbo([associated]), complemento([module, of, genes, using, 'co-expression', network, analysis])]). relacion([sujeto(['A', weighted, gene, 'co-expression', network, was, constructed, to, identify, gene, modules]), verbo([associated]), complemento([with, 'GC', resistance, in, 'MLL-rearranged', infant, 'ALL', patients])]). relacion([sujeto(['Significant', gene, ontology, '(', 'GO)', terms, and, signaling, pathways, enriched, in, relevant, modules, were, used, to]), verbo([provide]), complemento([guidance, towards, which, 'module(s)', consisted, of, promising, candidates, suitable, for, further, analysis])]). relacion([sujeto(['Subsequent', gene, set, net, correlation, analyses, of, the, novel, module]), verbo([provided]), complemento([further, support, for, its, validity, by, showing, that, the, 'S100', and, 'ANXA', genes, act, as, '\'', 'hub\'', genes, with, potentially, major, regulatory, roles, in, 'GC', 'sensitivity,', but, having, lost, this, role, in, the, 'GC', resistant, phenotype])]). relacion([sujeto(['From', our, data, we, conclude, that, available, systems, biology, approaches, can, be, employed, to, detect, new, candidate, genes, that, may]), verbo([provide]), complemento([further, insights, into, drug, resistance, of, 'MLL-rearranged', infant, 'ALL', cases])]). relacion([sujeto(['The', plants, employ, a, pair, of, 'near-infrared', fluorescent, 'nanosensors-single-walled', carbon, nanotubes, '(', 'SWCNTs)', conjugated, to, the, peptide, 'Bombolitin', 'II', to]), verbo([recognize]), complemento([nitroaromatics, via, infrared, fluorescent, 'emission,', and, 'polyvinyl-alcohol', functionalized, 'SWCNTs', that, act, as, an, invariant, reference, 'signal-embedded', within, the, plant, leaf, mesophyll])]). relacion([sujeto(['We']), verbo([found]), complemento([here, that, production, of, the, cytokine, 'IL-15', by, 'FRCs', was, essential, for, the, maintenance, of, group, 1, innate, lymphoid, cells, '(', 'ILCs)', in, 'Peyer\'s', patches, and, mesenteric, lymph, nodes])]). relacion([sujeto(['Moreover,', 'FRC-specific', ablation, of, the, innate, immunological, sensing, adaptor, 'MyD88', unleashed, 'IL-15', production, by, 'FRCs', during, infection, with, an, enteropathogenic, 'virus,', which]), verbo([led]), complemento([to, hyperactivation, of, group, 1, 'ILCs', and, substantially, altered, the, differentiation, of, helper, 'T', cells])]). relacion([sujeto(['Accelerated', clearance, of, virus, by, group, 1, 'ILCs', precipitated, severe, intestinal, inflammatory, disease, with, commensal, 'dysbiosis,']), verbo([loss]), complemento([of, intestinal, barrier, function, and, diminished, resistance, to, colonization])]). relacion([sujeto(['In', 'sum,', 'FRCs']), verbo([act]), complemento([as, an, '\'', 'on-demand\'', immunological, '\'', 'rheostat\'', by, restraining, activation, of, group, 1, 'ILCs', and, thereby, preventing, immunopathological, damage, in, the, intestine])]). relacion([sujeto(['The', 'Enterobacteriaceae', are, a, family, of, 'Gram-negative', bacteria, that, include, commensal, organisms, as, well, as, primary, and, opportunistic, pathogens, that, are, among, the]), verbo([leading]), complemento([causes, of, morbidity, and, mortality, worldwide])]). relacion([sujeto(['Microcins', are, small, secreted, proteins, that, possess, antimicrobial, activity, in, 'vitro,', but, whose, role, in, vivo]), verbo([has]), complemento([been, unclear])]). relacion([sujeto(['Our', work]), verbo([provides]), complemento([the, first, evidence, that, microcins, mediate, 'inter-', and, intraspecies, competition, among, the, 'Enterobacteriaceae', in, the, inflamed, gut])]). relacion([sujeto(['Moreover,', we, show, that, microcins, can]), verbo([act]), complemento([as, 'narrow-spectrum', therapeutics, to, inhibit, enteric, pathogens, and, reduce, enterobacterial, blooms])]). relacion([sujeto(['We', compared, results, of, a, modified, version, of, the, 'Asthma', 'Control', 'Test', using, parent, proxy]), verbo([report]), complemento(['(', 'PP-ACT)', with, results, reported, by, children, and, parents, using, the, validated, 'Childhood-Asthma', 'Control', 'Test', '(', 'C-ACT)'])]). relacion([sujeto(['Our', results]), verbo([suggest]), complemento([that, while, the, 'PP-ACT', missed, few, children, with, uncontrolled, asthma, and, may, simplify, reporting, of, asthma, control, in, circumstances, when, child, report, is, not, feasible, or, creates, barriers, to, survey, 'receipt,', limitations, of, proxy, reporting, should, be, considered])]). relacion([sujeto(['The', exercise, paradox, infers, 'that,', despite, the, 'well-established', cardioprotective, effects, of, repeated, episodic, exercise, '(', 'training),', the, risk, of, acute, atherothrombotic, events, may, be, transiently]), verbo([increased]), complemento([during, and, soon, after, an, exercise, bout])]). relacion([sujeto(['However,', the, acute, impact, of, different, exercise, modalities, on, platelet, function]), verbo([has]), complemento([not, previously, been, addressed])]). relacion([sujeto(['We', hypothesized, that, distinct, modalities, of, exercise, would]), verbo([have]), complemento([differing, effects, on, 'in vivo', platelet, activation, and, reactivity, to, agonists, which, induce, 'monocyte-platelet', aggregate, '(', 'MPA)', formation])]). relacion([sujeto(['Blood', samples, were, collected, 'before,', immediately, 'after,', and, 1, &, 'nbsp;h', after, each, 'intervention,', and, incubated, with, one, of, three, agonists, of, 'physiologically/clinically', relevant, pathways, of, platelet, activation, '(', thrombin, receptor]), verbo([activating]), complemento(['peptide-6', 'TRAP,', arachidonic, acid, 'AA,', and, 'cross-linked', 'collagen-related', peptide, 'xCRP)'])]). relacion([sujeto(['In', the, presence, of, 'AA,', 'TRAP,', and, 'xCRP,', both, 'RE', and, 'CARE', evoked]), verbo([increases]), complemento([in, 'MPAs', immediately, 'post-exercise', '(', 'P < 0'])]). relacion([sujeto([1, ')', ',', whereas, only, 'AA', significantly]), verbo([increased]), complemento(['MPAs', immediately, after, 'AE', '(', 'P < 0'])]). relacion([sujeto(['These']), verbo([increases]), complemento([in, platelet, activation, 'post-exercise', were, 'transient,', as, responses, approached, 'pre-exercise', levels, by, 1, &, 'nbsp;h'])]). relacion([sujeto(['These', are, the, first, data, to]), verbo([suggest]), complemento([that, exercise, involving, a, resistance, component, in, humans, may, transiently, increase, 'platelet-mediated', thrombotic, risk, more, than, aerobic, modalities])]). relacion([sujeto(['Genetic', correlations, may]), verbo([act]), complemento([as, 'constraints,', deflecting, the, evolutionary, response, from, the, direction, of, natural, selection])]). relacion([sujeto(['Some', parts, of, the, toad, 'skull,', such, as, the, 'snout,', may]), verbo([have]), complemento([functional, relevance, in, reproductive, 'ecology,', detecting, water, cues])]). relacion([sujeto(['Thus,', we, hypothesized, that, the, species, skull, divergence, was, driven, by, natural, selection]), verbo([associated]), complemento([with, climatic, variation])]). relacion([sujeto(['We', conclude, that, toad, species]), verbo([have]), complemento([responded, to, selection, related, to, climate, in, their, 'skulls,', yet, high, evolutionary, constraints, dominated, species, divergence, and, may, limit, species, responses, to, future, climate, change])]). relacion([sujeto(['Hippocampal', granule, cells, generated, in, the, weeks, before, and, after, an, epileptogenic, brain, injury, can, integrate, abnormally, into, the, dentate, 'gyrus,', potentially]), verbo([mediating]), complemento([temporal, lobe, epileptogenesis])]). relacion([sujeto(['Previous', studies]), verbo([have]), complemento([demonstrated, that, inhibiting, granule, cell, production, before, an, epileptogenic, brain, insult, can, mitigate, epileptogenesis])]). relacion([sujeto(['Diphtheria-toxin', receptor, expression, was]), verbo([induced]), complemento([among, granule, cells, born, up, to, 5, weeks, before, 'pilocarpine-induced', status, epilepticus, and, these, cells, were, then, eliminated, beginning, 3, d, after, the, epileptogenic, injury])]). relacion([sujeto(['This', treatment, produced, a, 50, '%', reduction, in, seizure, 'frequency,', but, also, a, 20, '%']), verbo([increase]), complemento([in, seizure, 'duration,', when, the, animals, were, examined, 2, months, later])]). relacion([sujeto(['These', findings]), verbo([provide]), complemento([the, first, 'proof-of-concept', data, demonstrating, that, granule, cell, ablation, therapy, applied, at, a, clinically, relevant, time, point, after, injury, can, have, 'disease-modifying', effects, in, epilepsy])]). relacion([sujeto(['This', work, also]), verbo([provides]), complemento([the, first, evidence, that, ablation, of, newly, generated, granule, cells, can, be, an, effective, therapy, when, begun, at, a, clinically, relevant, time, point, after, an, epileptogenic, insult])]). relacion([sujeto(['The', present, study, also, demonstrates, that, granule, cell, 'ablation,', while, reducing, seizure, 'frequency,', paradoxically]), verbo([increases]), complemento([seizure, duration])]). relacion([sujeto(['This', paradoxical, effect, may, reflect, a, disruption, of, homeostatic, mechanisms, that, normally]), verbo([act]), complemento([to, reduce, seizure, 'duration,', but, only, when, seizures, occur, frequently])]). relacion([sujeto(['Duchenne', muscular, dystrophy, '(', 'DMD)', is, a, genetic, disorder, that]), verbo([causes]), complemento([progressive, muscle, 'weakness,', ultimately, leading, to, early, mortality, in, affected, teenagers, and, young, adults])]). relacion([sujeto(['Previous', work, from, our, lab]), verbo([has]), complemento([shown, that, a, small, transmembrane, protein, called, sarcospan, '(', 'SSPN)', can, enhance, the, recruitment, of, adhesion, complex, proteins, to, the, cell, surface])]). relacion([sujeto(['When', human, 'SSPN', is]), verbo([expressed]), complemento([at, 'three-fold', levels, in, mdx, 'mice,', this, increase, in, adhesion, complex, abundance, improves, muscle, membrane, 'stability,', preventing, many, of, the, histopathological, changes, associated, with, 'DMD'])]). relacion([sujeto(['However,']), verbo([expressing]), complemento([higher, levels, of, human, 'SSPN', '(', 'ten-fold', transgenic, 'expression)', causes, a, severe, degenerative, muscle, phenotype, in, 'wild-type', mice])]). relacion([sujeto(['We', show, that, these, mice, exhibit]), verbo([increased]), complemento([resistance, to, eccentric, 'contraction-induced', damage, and, reduced, fatigue, following, exercise])]). relacion([sujeto(['This', disease, is]), verbo([caused]), complemento([by, a, single, mutation, leading, to, the, aspartate, 86, to, glycine, '(', 'D86G)', exchange, in, the, essential, nucleolar, 'RNA', methyltransferase, 'EMG1'])]). relacion([sujeto(['EMG1', is]), verbo([required]), complemento([for, the, synthesis, of, the, small, ribosomal, subunit, and, is, involved, in, modification, of, the, 18, 'S', ribosomal, 'RNA'])]). relacion([sujeto(['Here,', we, identify, the, 'pre-ribosomal', factors, 'NOP14,', 'NOC4L', and, 'UTP14A', as, members, of, a, nucleolar, subcomplex, that, contains, 'EMG1', and, is]), verbo([required]), complemento([for, its, recruitment, to, nucleoli])]). relacion([sujeto(['The', 'BCS', mutation, in, 'EMG1']), verbo([leads]), complemento([to, reduced, nucleolar, 'localisation,', accumulation, of, 'EMG1D86G', in, nuclear, foci, and, its, 'proteasome-dependent', degradation])]). relacion([sujeto(['Interestingly,', in, addition, to, its, role, in]), verbo([nuclear]), complemento(['import,', binding, of, the, 'Impβ/7', heterodimer, can, prevent, unspecific, aggregation, of, both, 'EMG1', and, 'EMG1D86G', on, 'RNAs', in, 'vitro,', indicating, that, the, importins, act, as, chaperones, by, binding, to, basic, regions, of, the, 'RNA', methyltransferase])]). relacion([sujeto(['Our', findings, further, indicate, that, in, 'Bowen-Conradi', 'syndrome,']), verbo([nuclear]), complemento([disassembly, of, the, import, complex, and, release, of, 'EMG1D86G', lead, to, its, nuclear, aggregation, and, 'degradation,', resulting, in, reduced, nucleolar, recruitment, of, the, 'RNA', methyltransferase, and, defects, in, the, biogenesis, of, the, small, ribosomal, subunit])]). relacion([sujeto(['This']), verbo([report]), complemento([details, the, blood, concentration, of, drugs, found, in, motorists, suspected, of, driving, under, the, influence, of, drugs, from, 2010, to, 2012, in, 'England', and, 'Wales'])]). relacion([sujeto(['This', study, was, carried, out, as, new, legislation]), verbo([has]), complemento([come, into, 'place,', setting, fixed, blood, concentration, limits, for, drugs, in, motorists])]). relacion([sujeto(['Given', its, medical, 'applications,', amphetamines, appear, to]), verbo([have]), complemento([been, grouped, with, the, medicinal, type, 'drugs,', with, our, data, showing, that, 25.2, '%', of, the, amphetamine, positive, samples, would, exceed, the, new, specified, limit])]). relacion([sujeto(['These', data, show, that, samples, containing, medicinal, and, prescription, drugs, are, likely, to, be, detected, below, the, new, legal, 'limits,', while, illicit, drugs, were, typically]), verbo([found]), complemento([at, concentrations, above, the, new, specified, limits])]). relacion([sujeto(['Many', of, these, 'blood-borne', glycosyltransferases, are]), verbo([associated]), complemento([with, pathological, 'states,', including, malignancies, and, inflammatory, conditions])]). relacion([sujeto(['Despite', the, potential, for, dynamic, modifications, of, glycans, on, distal, cell, surfaces, and, in, the, extracellular, 'milieu,', the, 'glycan-modifying', activities, present, in, systemic, circulation]), verbo([have]), complemento([not, been, systematically, examined])]). relacion([sujeto(['Here,', we, describe, an, evaluation, of, 'blood-borne', 'sialyl-,', 'galactosyl-', and, fucosyltransferase, activities, that]), verbo([act]), complemento([upon, the, four, common, terminal, glycan, precursor, 'motifs,', 'GlcNAc', 'monomer,', 'Gal(β3)GlcNAc,', 'Gal(β4)GlcNAc', and, 'Gal(β3)GalNAc,', to, produce, more, complex, glycan, structures])]). relacion([sujeto(['Data', from, radioisotope, assays, and, detailed, product, analysis, by, sequential, tandem, mass, spectrometry, show, that, blood]), verbo([has]), complemento([the, capacity, to, generate, many, of, the, 'well-recognized', and, important, glycan, 'motifs,', including, the, 'Lewis,', 'sialyl-Lewis,', 'H-', and, 'Sialyl-T', antigens])]). relacion([sujeto(['Platelets', compartmentalize, glycosyltransferases, and]), verbo([release]), complemento([them, upon, activation])]). relacion([sujeto(['This', paper]), verbo([reports]), complemento([the, protocol, of, a, randomised, controlled, trial, of, an, innovative, and, translatable, online, 'intervention,', parenting, acceptance, and, commitment, therapy, '(', 'PACT),', for, families, of, children, with, 'CP'])]). relacion([sujeto(['We', predict, that]), verbo([participating]), complemento([in, the, 'PACT', programme, will, be, associated, with, improvements, in, the, 'parent-child', 'relationship,', in, child, functioning, and, in, adjustment, and, quality, of, life, for, both, parent, and, child])]). relacion([sujeto(['We', aim, to]), verbo([recruit]), complemento([66, parents, of, children, '(', 2, -, 10, years, 'old)', diagnosed, with, 'CP', to, this, study])]). relacion([sujeto(['Ethics', approvals]), verbo([have]), complemento([been, obtained, through, the, 'Children\'s', 'Health', 'Queensland', 'Hospital', and, 'Health', 'Service', 'Human', 'Research', 'Ethics', 'Committee', '(', 'HREC/15/QRCH/115)', and, 'The', 'University', of, 'Queensland', '(', 2015001743, ')'])]). relacion([sujeto(['If', efficacy, is, 'demonstrated,', then, the, 'PARENT101', course]), verbo([has]), complemento([the, potential, to, be, disseminated, widely, in, an, accessible, manner, and, at, minimal, cost])]). relacion([sujeto(['Further,', the, 'PACT', framework, may]), verbo([provide]), complemento([a, blueprint, for, similar, online, courses, with, parents, in, a, full, range, of, contexts])]). relacion([sujeto(['Mammalian', genomes, contain, hundred, of, thousands, 'L1s', that]), verbo([have]), complemento([accumulated, since, the, origin, of, mammals])]). relacion([sujeto(['A', single, group, of, very, similar, elements, is, active, at, a, time, in, 'mammals,', thus, a, single, lineage, of, active, families]), verbo([has]), complemento([evolved, in, this, group])]). relacion([sujeto(['The', most, variation, is]), verbo([found]), complemento([in, the, 5, '\'', 'UTR,', which, is, longer, in, 'amniotes,', and, in, the, 'ORF1,', which, tend, to, evolve, faster, in, mammals])]). relacion([sujeto(['The', highly, divergent, 'L1', families, of, 'lizard,', frog, and, fish, share, 'species-specific', features]), verbo([suggesting]), complemento([they, are, subjected, to, the, same, functional, constraints, imposed, by, their, host])]). relacion([sujeto(['The', relative, conservation, of, the, 5, '\'', 'UTR', and, 'ORF1', in, 'non-mammalian', vertebrates]), verbo([suggests]), complemento([that, the, repression, of, transposition, by, the, host, does, not, act, in, a, sequence, specific, manner, and, did, not, result, in, an, arms, 'race,', as, is, observed, in, mammals])]). relacion([sujeto(['In', type, 2, diabetes, and, 'obesity,', circulating, 'RBP4', is]), verbo([increased]), complemento([and, may, act, systemically, to, cause, 'insulin-resistance', and, glucose, intolerance])]). relacion([sujeto(['Observations', that, adipocyte, 'RBP4', mRNA]), verbo([increases]), complemento([in, parallel, with, circulating, 'RBP4', in, these, 'conditions,', whereas, liver, 'RBP4', mRNA, does, 'not,', led, to, a, widely, held, hypothesis, that, elevated, circulating, 'RBP4', is, a, direct, result, of, increased, production, by, adipocytes])]). relacion([sujeto(['Adipose', tissue, 'RBP4', expression, and, secretion, remain, intact, in, 'LRKO', 'mice,', and]), verbo([increase]), complemento([as, expected, in, the, setting, of, 'diet-induced', 'insulin-resistance'])]). relacion([sujeto(['A', group, of, interprofessional, healthcare, faculty]), verbo([provided]), complemento([a, weeklong, interprofessional, immersion, for, 'doctoral-level', healthcare, trainees, '(', 'n = 24)', in, 'Pharmacy,', 'Counselling', 'Psychology,', 'Nursing,', and, 'Family', 'Medicine', residents])]). relacion([sujeto(['Healthcare', faculty, and, staff, from, each, profession, worked, 'side-by-side', to]), verbo([provide]), complemento([integrated, training, utilising, the, 'Interprofessional', 'Education', 'Collaborative', core, competency, domains])]). relacion([sujeto(['Trainees', were, placed, into, small, teams, with, representatives, from, each, 'profession;', each, team, 'observed,', 'learned,', and, practiced, working, within, teams, to]), verbo([provide]), complemento([quality, patient, care])]). relacion([sujeto(['The', results]), verbo([suggest]), complemento([that, after, completing, the, 'training,', trainees, felt, more, confident, in, their, ability, to, work, within, an, interprofessional, team, and, more, likely, to, utilise, a, 'team-based', approach, in, the, future])]). relacion([sujeto(['Objective:', 'The', unique, characteristics, of, sexual, assault, '(', 'SA)-a', toxic, mix, of, an, interpersonal, 'harm,', a, violent, exploitation, of, 'one\'s', 'body,', and, a, transformation, of, an]), verbo([act]), complemento([of, connectedness, into, an, act, of, 'submission-are', postulated, to, negatively, affect, the, 'self-concept'])]). relacion([sujeto(['Results:', 'Sexually', assaulted, women, without, 'PTSD']), verbo([reported]), complemento([impaired, 'self-concept', as, compared, with, 'NT', women])]). relacion([sujeto(['The', importance, of, adopting, a, multifaceted, conceptualization, of, the, self, to]), verbo([gain]), complemento([a, deeper, understanding, of, the, aftermath, of, trauma, is, highlighted])]). relacion([sujeto(['(', 'PsycINFO', 'Database', 'Record', 'Graphene', membranes]), verbo([act]), complemento([as, highly, sensitive, transducers, in, nanoelectromechanical, devices, due, to, their, ultimate, thinness])]). relacion([sujeto(['Previously,', the, piezoresistive, effect]), verbo([has]), complemento([been, experimentally, verified, in, graphene, using, uniaxial, strain, in, graphene])]). relacion([sujeto(['Here,', we]), verbo([report]), complemento([experimental, and, theoretical, data, on, the, 'uni-', and, biaxial, piezoresistive, properties, of, suspended, graphene, membranes, applied, to, piezoresistive, pressure, sensors])]). relacion([sujeto(['The', gauge, factor, is]), verbo([found]), complemento([to, be, practically, independent, of, the, doping, concentration, and, crystallographic, orientation, of, the, graphene, films])]). relacion([sujeto(['These', investigations]), verbo([provide]), complemento([deeper, insight, into, the, piezoresistive, behavior, of, graphene, membranes])]). relacion([sujeto(['However,', the, mechanisms, underlying, this]), verbo([increased]), complemento([resistance, to, apoptosis, in, these, mature, neurons, are, not, completely, understood])]). relacion([sujeto(['We']), verbo([have]), complemento([previously, found, that, members, of, the, 'miR-29', family, of, microRNAs, '(', 'miRNAs)', are, induced, with, neuronal, maturation, and, that, overexpression, of, 'miR-29', was, sufficient, to, restrict, apoptosis, in, neurons])]). relacion([sujeto(['To', determine, whether, endogenous, 'miR-29', alone, was, responsible, for, the, inhibition, of, cytochrome, c]), verbo([release]), complemento([in, mature, 'neurons,', we, examined, the, status, of, the, apoptotic, pathway, in, sympathetic, neurons, deficient, for, all, three, 'miR-29', family, members])]). relacion([sujeto(['Unexpectedly,', we]), verbo([found]), complemento([that, the, apoptotic, pathway, remained, largely, restricted, in, 'miR-29-deficient', mature, neurons])]). relacion([sujeto(['We', identify, 'miR-24', as, another, miRNA, that, is, upregulated, in, the, maturing, cerebellum, and, sympathetic, neurons, that, can]), verbo([act]), complemento([redundantly, with, 'miR-29', by, targeting, a, similar, repertoire, of, prodeath, 'BH3-only', genes])]). relacion([sujeto(['Overall,', our, results]), verbo([reveal]), complemento([that, mature, neurons, engage, multiple, redundant, brakes, to, restrict, the, apoptotic, pathway, and, ensure, their, 'long-term', survival])]). relacion([sujeto(['Testosterone', '(', 'T)', is, an, important, mediator, of, reproductive, behaviours, and, potential]), verbo([target]), complemento([for, selection])]). relacion([sujeto(['Here,', we, used, the, 'GnRH', challenge, '(', an, injection, of, 'gonadotropin-releasing', hormone, which]), verbo([stimulates]), complemento([maximal, 'T', 'release),', to, examine, how, individual, differences, in, 'T', relate, to, reproductive, success, and, how, 'T', changes, across, date, and, breeding, stage])]). relacion([sujeto(['Our', results]), verbo([suggest]), complemento([that, 'T', production, ability, is, an, important, target, for, selection, and, that, when, males, invest, heavily, in, parental, care, they, reduce, their, sensitivity, to, 'GnRH'])]). relacion([sujeto(['Although', 'MT1XT20', was, earlier]), verbo([reported]), complemento([as, a, valid, standalone, marker, for, 'MSI', testing, in, 'CRC', 'patients,', we, could, not, verify, this, in, our, 'Iranian', patients])]). relacion([sujeto(['Therefore,', it, seems, 'BAT26', could]), verbo([act]), complemento([well, as, a, single, marker, for, 'MSI', testing, in, 'Iranian', 'CRC', patients])]). relacion([sujeto(['Preschoolers', '(', 3, -, to, 4, -, 'year-olds)', and, kindergarteners, '(', 5, -, to, 6, -, 'year-olds;', 'N = 111)']), verbo([participated]), complemento([in, a, resource, distribution, task, in, which, they, had, to, consider, both, the, 'recipients\'', group, membership, '(', minimal, 'color-based', 'groups),', and, their, own, 'teachers\'', preferences, regarding, how, to, distribute, '(', give, &, 'quot;all"', or, &, 'quot;none")'])]). relacion([sujeto(['Thus,', boys, exploited, an, 'authority\'s', legitimization, to]), verbo([act]), complemento(['antisocially,', according, to, a, parochial, bias])]). relacion([sujeto(['Although', it]), verbo([has]), complemento([been, proposed, that, only, the, latter, may, act, as, a, mediator, of, the, relationship, between, stress, and, cardiovascular, 'disease,', both, functional, and, dysfunctional, forms, of, repetitive, thinking, have, been, associated, with, blood, pressure, '(', 'BP)', reactivity, of, the, same, magnitude])]). relacion([sujeto(['However,', a, similar, 'BP', reactivity, may, be]), verbo([caused]), complemento([by, different, physiological, 'determinants,', which, may, differ, in, their, risk, for, cardiovascular, pathology])]). relacion([sujeto(['Perseverative', cognition, and, problem, solving, '(', but, not, mind, 'wandering)', elicited, 'BP']), verbo([increases]), complemento([of, similar, magnitude])]). relacion([sujeto(['Given', that, high, vascular, resistance, and, delayed, recovery, are, the, hallmarks, of, hypertension, the, results]), verbo([suggest]), complemento([a, potential, mechanism, through, which, perseverative, cognition, may, act, as, a, mediator, in, the, relationship, between, stress, and, risk, for, developing, precursors, to, cardiovascular, disease])]). relacion([sujeto(['Microorganisms,', or, 'microbes,', can, function, as, threatening, pathogens, that]), verbo([cause]), complemento([disease, in, 'humans,', 'animals,', and, 'plants;', 'however,', they, also, act, as, litter, decomposers, in, natural, ecosystems])]). relacion([sujeto(['As', the, outermost, barrier, and, interface, with, the, 'environment,', the, microbial, cell, surface, is, crucial, for, 'cell-to-cell', communication, and, is, a, potential]), verbo([target]), complemento([of, chemotherapeutic, agents])]). relacion([sujeto(['Surface', ultrastructures, of, microbial, cells]), verbo([have]), complemento([typically, been, observed, using, scanning, electron, microscopy, '(', 'SEM)', and, atomic, force, microscopy, '(', 'AFM)'])]). relacion([sujeto(['Owing', to, its, characteristics, of, 'low-temperature', specimen, preparation, and, superb, resolution, '(', down, to, 1, 'nm),', 'cryo-field', emission, 'SEM']), verbo([has]), complemento([revealed, paired, 'rodlets,', referred, to, as, 'hydrophobins,', on, the, cell, walls, of, bacteria, and, fungi])]). relacion([sujeto(['Recent', technological, advances, in, 'AFM']), verbo([have]), complemento([enabled, 'high-speed', live, cell, imaging, in, liquid, at, the, nanoscale, 'level,', leading, to, clear, visualization, of, 'cell-drug', interactions])]). relacion([sujeto(['Platinum-carbon', replicas, from, 'freeze-fractured', fungal, spores]), verbo([have]), complemento([been, observed, using, transmission, electron, 'microscopy,', revealing, hydrophobins, with, varying, dimensions])]). relacion([sujeto(['In', 'addition,', 'AFM']), verbo([has]), complemento([been, used, to, resolve, bacteriophages, in, their, free, state, and, during, infection, of, bacterial, cells])]). relacion([sujeto(['Various', microscopy, techniques, with]), verbo([enhanced]), complemento([spatial, 'resolution,', imaging, 'speed,', and, versatile, specimen, preparation, are, being, used, to, document, cellular, structures, and, 'events,', thus, addressing, unanswered, biological, questions])]). relacion([sujeto(['Recent', research, progress]), verbo([has]), complemento([revealed, that, a, novel, type, of, interstitial, cells, termed, cardiac, telocytes, '(', 'CTs)', is, found, in, the, interstitium, of, the, heart])]). relacion([sujeto(['Furthermore,', we, 'demonstrated,', for, the, first, 'time,', that, transplantation, of, 'CTs', in, cases, of, 'MI']), verbo([decreases]), complemento([the, infarct, size, and, improves, myocardial, function])]). relacion([sujeto(['The', mechanisms, behind, the, beneficial, effects, of, 'CT', transplantation, are]), verbo([increased]), complemento([angiogenesis, at, the, infarct, site, and, the, border, 'zone,', decreased, fibrosis, in, the, infarct, and, 'non-infarct', 'zones,', improved, pathological, reconstruction, of, the, left, 'ventricle,', and, increased, regeneration, of, 'CTs', in, the, infarct, zone])]). relacion([sujeto(['Our', findings]), verbo([reveal]), complemento([that, 'CTs', can, be, specifically, identified, by, the, following, 'characteristics:', very, small, cell, 'bodies,', extreme, prolongation, with, some, 'dilation,', predisposition, to, cell, death, under, 'ischemia,', and, expression, of, molecular, markers, such, as, 'c-Kit,', 'CD34,', 'vimentin,', and, 'PDGFR-β'])]). relacion([sujeto(['CTs']), verbo([act]), complemento([as, a, structural, and, functional, niche, microenvironment, in, the, myocardium, and, play, an, essential, role, in, maintaining, the, integrity, of, the, myocardium, and, in, the, regeneration, of, damaged, myocardium])]). relacion([sujeto(['The', telocytes]), verbo([have]), complemento([recently, been, described, in, the, prostate, gland])]). relacion([sujeto(['In', this, 'chapter,', our, group, gives, a, brief, introduction, to, telocytes, and, explores, the, history, that]), verbo([led]), complemento([to, such, a, concept, and, then, discusses, hypotheses, and, presents, new, evidences, about, the, roles, exerted, by, telocytes, in, the, prostate])]). relacion([sujeto(['First', is, given, emphasis, on, the, role, that, these, cells, possibly, play, in, paracrine, signaling, employed, in, the, differentiation, of, smooth, muscle, periacinar, are, then, discussed, other, roles, potentially, performed, by, telocytes, in, the, 'prostate,', such, as, the, 'organizational,', where, these, cells, would]), verbo([act]), complemento([in, order, to, delimit, stromal, 'microenvironments,', thereby, assisting, the, differentiation, of, the, prostatic, anatomical, components])]). relacion([sujeto(['Over', the, last, few, 'years,', in, vitro, 'models,', based, on, 'patient-derived']), verbo([induced]), complemento([pluripotent, stem, cells, '(', 'iPSCs),', have, received, considerable, attention, for, modeling, different, neurodegenerative, disorders])]). relacion([sujeto(['These', genes, may]), verbo([act]), complemento([as, a, gear, unit, between, the, 'PD', progression, and, the, deregulation, of, the, immune, system])]). relacion([sujeto(['Depressive', symptoms, are, reportedly, common, in, asthma, and]), verbo([have]), complemento([been, related, to, poor, disease, 'control,', but, the, mechanism, of, this, association, is, still, unclear])]). relacion([sujeto(['Poor', quality, 'sleep,', frequently, observed, in, 'asthmatics,', is, also, a, manifestation, of, depression, and]), verbo([has]), complemento([been, related, to, uncontrolled, asthma])]). relacion([sujeto(['Inadequate', asthma, control, '(', 'ACT', &, 'lt;20)', was]), verbo([found]), complemento([in, 94, '(', 76.4, &, 'nbsp;%)', 'subjects,', depressive, symptoms, in, 92, '(', 74.8, &, 'nbsp;%),', poor, quality, sleep, '(', 'PSQI', &, 'gt;5)', in, 99, '(', 80.49, &, 'nbsp;%),', and, excessive, daytime, sleepiness, '(', 'ESS', '≥10)', in, 34, '(', 27.64, &, 'nbsp;%)'])]). relacion([sujeto(['Depressive', symptoms, were]), verbo([associated]), complemento([with, both, poor, quality, sleep, '(', 'R = 0'])]). relacion([sujeto(['Asthma', control, in, women, is, independently]), verbo([associated]), complemento([with, depressive, symptoms, and, quality, of, 'sleep,', suggesting, that, these, patients, might, benefit, from, simple, measures, to, promote, healthy, sleep, behavior, and, sleep, hygiene, and, also, that, routine, screening, for, depression, can, be, 'relevant,', 'particularly,', in, poorly, controlled, cases])]). relacion([sujeto(['In', this, 'report,', a, novel, 'one-step', chemical, reduction, method, was]), verbo([reported]), complemento([for, synthesis, of, 'water-soluble', and, stable, fluorescent, 'glutathione-templated', silver, nanocluster, '(', 'GSH-Ag', 'NCs)', with, ascorbic, acid, as, an, 'environmental-friendly', reducing, agent])]). relacion([sujeto(['On', the, basis, of, an, 'oxidoreduction-induced', fluorescence, quenching, 'mechanism,', the, prepared, 'GSH-Ag', 'NCs']), verbo([found]), complemento([to, act, as, a, 'cheap,', 'non-toxic', and, highly, sensitive, &, 'quot;turn-off"', fluorophore, for, ascorbic, acid, '(', 'AA)'])]). relacion([sujeto(['The', probe, for, 'Arg,', in, 'turn,']), verbo([has]), complemento([a, linear, range, in, the, 10, -, 180, &, 'nbsp;μM', concentration, 'range,', and, the, limit, of, detection, is, 0.5, &, 'nbsp;μM'])]). relacion([sujeto(['Depending', on, the, context, of, 'inflammation,', 'IL-22', can]), verbo([have]), complemento([protective, or, inflammatory, effects, on, epithelial, cells])]). relacion([sujeto(['This', dual, nature, of, 'IL-22']), verbo([leads]), complemento([us, to, hypothesize, that, its, activity, must, be, exquisitely, regulated, to, prevent, host, tissue, damage])]). relacion([sujeto(['Environmental', factors, may]), verbo([act]), complemento([as, a, cellular, cue, as, to, how, cells, respond, to, 'IL-22'])]). relacion([sujeto(['Inflammatory', environments, are, characterized, by, low, oxygen, and, thus, we, examined, whether, cells]), verbo([respond]), complemento([differently, to, 'IL-22', hypoxia, compared, with, normoxia])]). relacion([sujeto(['IL-22', stimulation, of, hepatocytes, incubated, in, low, oxygen]), verbo([led]), complemento([to, reduced, levels, of, activated, signal, transducer, and, activator, of, transcription, 3, and, further, downstream, effects, such, as, reduced, induction, of, the, 'anti-microbial', 'protein,', 'lipocalin-2'])]). relacion([sujeto(['Thus,', hypoxia, that, accompanies, chronic, inflammation, may, be, a, mechanism, to]), verbo([regulate]), complemento([the, bioactivity, of, the, 'dual-natured', 'IL-22', cytokine])]). relacion([sujeto(['A', smart, 'magnetic-targeting', drug, carrier, 'γ-Fe2O3@p-silica', comprising, a, 'γ-Fe2O3', core, and, porous, shell]), verbo([has]), complemento([been, prepared, and, characterized])]). relacion([sujeto(['The', particles]), verbo([have]), complemento([a, uniform, size, of, about, 60, 'nm,', and, a, porous, shell, of, thickness, 3, nm])]). relacion([sujeto(['It', was]), verbo([found]), complemento([that, the, 'RB', was, released, rapidly, at, pH, 5.5, but, at, pH, 7.4, the, rate, and, extent, of, release, was, greatly, attenuated])]). relacion([sujeto(['A', clear, 'dose-dependent', contrast, enhancement, in, both, 'T', 1, -, weighted, and, 'T', 2, -, weighted, 'MR', images, indicated, the, potential, of, the, 'γ-Fe2O3@p-silica', particles, to]), verbo([act]), complemento([as, 'dual-mode', 'T', 1, and, 'T', 2, 'MRI', contrast, agents])]). relacion([sujeto(['To', examine, how, the, right, to, participation, according, to, 'Article', 19, of, the, 'United', 'Nations\'', 'Convention', on, the, 'Rights', of, 'Persons', with, 'Disabilities', '(', 'UNCRPD)', is]), verbo([promoted]), complemento([by, personal, assistance, use, in, 'Sweden', across, 'age,', gender, and, eligible, person, categories])]). relacion([sujeto(['Significant', differences, in, personal, assistance]), verbo([reported]), complemento([were, found, between, children, and, 'adults,', men, and, women, and, between, the, three, eligible, person, categories])]). relacion([sujeto(['The', discrepancy, between]), verbo([reported]), complemento([and, expected, outcome, of, personal, assistance, indicates, that, 'Article', 19, of, the, 'UNCRPD', has, not, been, met])]). relacion([sujeto(['The', unequal, access, to, participation, across, 'age,', gender, and, eligible, person, categories, would, seem, to, further, signify, that, the, 'Act', concerning, 'Support', and, 'Service', for, 'Persons', with, 'Certain', 'Functional', 'Impairments', is]), verbo([promoting]), complemento([activities, of, a, caring, nature, rather, than, fulfilling, 'Article', 19, of, the, 'UNCRPD,', i])]). relacion([sujeto(['Men']), verbo([reported]), complemento([more, personal, assistance, use, for, activities, promoting, participation, than, women])]). relacion([sujeto(['The', discrepancy]), verbo([found]), complemento([between, reported, and, expected, outcome, of, personal, assistance, underlines, the, importance, of, service, providers, and, administrative, officials, being, sensitive, to, policy, intentions])]). relacion([sujeto(['There', is, a, need, of, guidelines, for, service, providers, and, administrative, officials, to]), verbo([promote]), complemento([disability, rights, of, participation, for, persons, eligible, for, personal, assistance])]). relacion([sujeto(['These', results]), verbo([have]), complemento([serious, implications, on, the, 'health and', safety, of, employees, in, the, workplace])]). relacion([sujeto(['The', implementation, of, the, 'South', 'African', 'Mental', 'Health', 'Care', 'Act,', which, 'regulates care', for, clients, with, intellectual, 'disabilities,', impacted, on, the, healthcare, services]), verbo([provided]), complemento(['to this', population])]). relacion([sujeto(['This', study]), verbo([provided]), complemento([preliminary, evidence, that, these, two, tools, are, 'valuable instruments', for, measuring, occupational, performance, and, adaptive, functioning, in, 'institutions that', provide, care, for, this, vulnerable, and, 'under-researched', population])]). relacion([sujeto(['Interactions', between, oligodendrocyte, precursor, cells, '(', 'OPCs)', and, developing, axons]), verbo([regulate]), complemento([the, formation, of, myelin, around, axons])]). relacion([sujeto(['We', now, 'show,', using, organotypic, cerebral, cortex, slices, from, mice]), verbo([expressing]), complemento([eGFP, in, 'Sox10-positive', 'oligodendrocytes,', that, endogenously, released, 'GABA,', acting, on, 'GABAA', 'receptors,', greatly, reduces, the, number, of, oligodendrocyte, lineage, cells])]). relacion([sujeto(['The']), verbo([decrease]), complemento([in, oligodendrocyte, number, correlates, with, a, reduction, in, the, amount, of, myelination, but, also, an, increase, in, internode, 'length,', a, parameter, previously, thought, to, be, set, by, the, axon, diameter, or, to, be, a, property, intrinsic, to, oligodendrocytes])]). relacion([sujeto(['Importantly,', while, 'TTX', block, of, neuronal, activity, had, no, effect, on, oligodendrocyte, lineage, cell, number, when, applied, 'alone,', it, was, able, to, completely, abolish, the, effect, of, blocking, 'GABAA', 'receptors,']), verbo([suggesting]), complemento([that, control, of, myelination, by, endogenous, 'GABA', may, require, a, permissive, factor, to, be, released, from, axons])]). relacion([sujeto(['These', results, imply, 'that,', during, 'development,', 'GABA', can]), verbo([act]), complemento([as, a, local, environmental, cue, to, control, myelination, and, thus, influence, the, conduction, velocity, of, action, potentials, within, the, 'CNS'])]). relacion([sujeto(['Responsive', medicine, is, an, appropriate, training, method, which, trains, the, graduates, who, can]), verbo([act]), complemento([effectively, in, initial, and, secondary, aspects, of, health, issues, in, the, society])]). relacion([sujeto(['The']), verbo([target]), complemento([population, of, this, study, was, all, the, students, of, the, 'Nutrition', and, 'Health', 'School', of, 'Shiraz', 'University', of, 'Medical', 'Sciences'])]). relacion([sujeto(['Increasing', evidence]), verbo([suggests]), complemento([that, cancer, stem, cells, '(', 'CSCs)', are, a, key, occurrence, in, the, process, of, many, human, cancers])]). relacion([sujeto(['Lung', cancer, is, the, most, common, aggressive, malignancy, and]), verbo([cause]), complemento([of, cancer, death, worldwide])]). relacion([sujeto(['The', research, on, lung, cancer, stem, cells]), verbo([has]), complemento([been, highlighted, for, many, years])]). relacion([sujeto(['MicroRNAs', '(', 'miRNAs),', a, class, of, newly, emerging, small, noncoding, 'RNAs', that]), verbo([act]), complemento([as, 'post-transcriptional', regulators, of, gene, 'expression,', have, been, demonstrated, to, serve, as, a, vital, player, in, 'fine-tuning', a, number, of, biological, activities, ranging, from, embryogenesis, to, programmed, cell, death, as, well, as, tumourigenesis])]). relacion([sujeto(['In', recent, 'years,', several, miRNAs]), verbo([have]), complemento([been, highlighted, to, be, specifically, expressed, in, 'CSCs'])]). relacion([sujeto(['As', 'such,', many, miRNAs]), verbo([have]), complemento([been, shown, to, regulate, 'self-renewal', and, differentiation, properties, of, 'CSCs'])]). relacion([sujeto(['In', this, 'review,', we, present, the, latest, findings, on, miRNAs, that]), verbo([regulate]), complemento([the, tumour, microenvironment, of, lung, 'CSCs', with, the, goal, to, prompt, the, development, of, novel, therapeutic, strategies, for, patients, with, lung, cancer])]). relacion([sujeto(['Shank', proteins, '(', 'Shank1,', 'Shank2,', and, 'Shank3)']), verbo([act]), complemento([as, scaffolding, molecules, in, the, postsynaptic, density, of, many, excitatory, neurons])]). relacion([sujeto(['Mutations', in, 'SHANK', 'genes,', in, particular, 'SHANK2', and, 'SHANK3,']), verbo([lead]), complemento([to, autism, spectrum, disorders, '(', 'ASD)', in, both, human, and, mouse, models])]). relacion([sujeto(['Via', various]), verbo([binding]), complemento([partners, of, these, 'domains,', 'Shank3', is, able, to, bind, and, interact, with, a, wide, range, of, proteins, including, modulators, of, small, 'GTPases', such, as, 'RICH2,', a, 'RhoGAP', 'protein,', and, 'βPIX,', a, 'RhoGEF', protein, for, 'Rac1', and, 'Cdc42,', actin, binding, proteins, and, actin, modulators])]). relacion([sujeto(['Dysregulation', of, all, isoforms, of, 'Shank', 'proteins,', but, especially, 'Shank3,']), verbo([leads]), complemento([to, alterations, in, spine, 'morphogenesis,', 'shape,', and, activity, of, the, synapse, via, altering, actin, dynamics])]). relacion([sujeto(['Therefore,', 'here,', we, highlight, the, role, of, 'Shank', proteins, as, modulators, of, small, 'GTPases', 'and,', 'ultimately,', actin, 'dynamics,', as]), verbo([found]), complemento([in, multiple, in, vitro, and, in, vivo, models])]). relacion([sujeto(['The', failure, to]), verbo([mediate]), complemento([this, regulatory, role, might, present, a, shared, mechanism, in, the, pathophysiology, of, 'autism-associated', 'mutations,', which, leads, to, dysregulation, of, spine, morphogenesis, and, synaptic, signaling])]). relacion([sujeto(['Supramolecular', brush, copolymers]), verbo([have]), complemento([attracted, continuing, interest, due, to, their, unusual, 'architectures,', fascinating, 'properties,', and, potential, applications, in, many, fields, involving, smart, 'stimuli-responsive', drug, delivery, systems])]). relacion([sujeto(['Encapsulation', of, anticancer, drug, doxorubicin, '(', 'DOX)']), verbo([caused]), complemento([deactivation, of, the, fluorescences, of, both, the, tetraphenylethene, '(', 'TPE)', and, 'DOX', chromophores, due, to, the, energy, transfer, relay, '(', 'ETR)', 'effect,', mediated, by, 'Förster', resonance, energy, transfer, '(', 'FRET)', and, 'aggregation-caused', quenching, '(', 'ACQ)'])]). relacion([sujeto(['The']), verbo([release]), complemento([of, loaded, 'DOX', molecules, can, be, triggered, by, low, pH, and, 'reductase,', recovering, the, &, 'quot;silenced"', fluorescence, caused, by, the, interruption, of, the, 'ETR', 'effect,', achieving, in, situ, visualization, of, the, drug, release, process, by, observing, the, location, and, magnitude, of, the, energy, 'transfer-dependent', fluorescence, variation])]). relacion([sujeto(['The', biotin, ligands, on, the, surfaces, of, the, 'DOX-loaded', 'SNPs']), verbo([act]), complemento([as, targeting, agents, to, deliver, 'DOX', preferentially, to, cancer, cells, 'over-expressing', biotin, receptor])]). relacion([sujeto(['Therefore,', 'FAEs']), verbo([act]), complemento([as, accessory, enzymes, to, assist, xylanolytic, and, pectinolytic, enzymes, in, gaining, access, to, their, site, of, action, during, biomass, conversion])]). relacion([sujeto(['Their', ability, to]), verbo([release]), complemento([ferulic, acid, and, other, hydroxycinnamic, acids, from, plant, biomass, makes, 'FAEs', potential, biocatalysts, in, a, wide, variety, of, applications, such, as, in, 'biofuel,', food, and, 'feed,', pulp, and, 'paper,', 'cosmetics,', and, pharmaceutical, industries])]). relacion([sujeto(['This', review]), verbo([provides]), complemento([an, updated, overview, of, the, knowledge, on, fungal, 'FAEs,', in, particular, describing, their, role, in, plant, biomass, 'degradation,', diversity, of, their, biochemical, properties, and, substrate, 'specificities,', their, regulation, and, conditions, needed, for, their, induction])]). relacion([sujeto(['This']), verbo([has]), complemento([led, to, a, new, subfamily, classification, of, fungal, 'FAEs', that, takes, into, account, both, phylogeny, and, substrate, specificity])]). relacion([sujeto(['Analysis', of, 'SSCs', markers, and, transplantation, results, revealed, that, the, cultured, spermatogonia]), verbo([retained]), complemento([stem, cell, characteristics, after, 'long-term', in, vitro, propagation])]). relacion([sujeto(['Immunostaining', showed, that, 'BMP4', was, predominantly]), verbo([expressed]), complemento([in, germ, cells, and, that, its, level, increased, as, spermatogenesis, progresses])]). relacion([sujeto(['While', exogenous, 'BMP4', by, itself, did, not]), verbo([induce]), complemento([the, expression, of, 'Stra8', and, 'c-Kit,', two, marker, genes, of, differentiating, 'spermatogonia,', a, significant, cooperative, effect, of, 'BMP4', and, retinoic, acid, '(', 'RA)', was, observed])]). relacion([sujeto(['Moreover,', pretreatment, of, cultured, spermatogonia, with, the, 'BMP4', antagonist, 'Noggin', could]), verbo([inhibit]), complemento(['RA-induced', expression, of, these, two, marker, genes])]). relacion([sujeto(['In', 'conclusion,', 'BMP4', may, exert, autocrine, effects, and]), verbo([act]), complemento([cooperatively, with, 'RA', to, induce, the, differentiation, of, spermatogonia, in, vivo])]). relacion([sujeto(['With', the, development, of, urban, setting, 'worldwide,', the, major, issue, of, concern, is, the]), verbo([increase]), complemento([in, the, mortality, rate, in, the, population, due, to, road, traffic, accidents])]). relacion([sujeto(['The', 'face,', being, the, most, exposed, region, is, susceptible, to, injuries, and, maybe]), verbo([associated]), complemento([with, injuries, to, the, adjacent, 'neuro-cranium'])]). relacion([sujeto(['The', literature]), verbo([has]), complemento([conflicting, views, on, the, relationship, between, facial, fractures, and, head, injuries, with, some, authors, opining, that, the, facial, skeleton, cushions, the, brain, while, some, other, authors, claim, that, the, facial, fractures, act, as, indicators, for, head, injuries])]). relacion([sujeto(['To', analyze, the, correlation, between, the, facial, fractures, and, head, injuries, and, to, assess, if, the, facial, skeleton]), verbo([acts]), complemento([to, protect, the, brain, from, injury])]). relacion([sujeto(['A', prospective, study, that, included, patients, who]), verbo([reported]), complemento([to, the, emergency, department, of, 'Basaveswar', 'Teaching', and, 'General', 'Hospital,', 'Gulbarga,', during, 2, 'years,', between, 'August', 2013, and, 'July', 2015, was, conducted])]). relacion([sujeto(['The', 'Glasgow', 'Coma', 'Scale', score, was, significantly, lower, in, patients, with]), verbo([associated]), complemento([head, injuries, as, compared, to, those, patients, with, facial, trauma, alone])]). relacion([sujeto(['The', mortality, rate, in, the, study, was, 2, '%', with, both, the, victims, having, sustained, middle, third, and, upper, third, fractures, respectively, with]), verbo([associated]), complemento([head, injuries])]). relacion([sujeto(['The', facial, skeleton, does, not]), verbo([act]), complemento([to, cushion, the, brain, from, injury, 'but,', in, 'fact,', the, facial, trauma, victims, should, be, considered, potential, head, injury, patients])]). relacion([sujeto(['Because', thiol, groups]), verbo([act]), complemento([as, 'anti-inflammatory', 'mediators,', the, alteration, in, the, 'thiol-disulphide', homeostasis, may, be, involved, in, brucellosis])]). relacion([sujeto(['We', recently]), verbo([reported]), complemento([that, the, 'segment-specific', noncoding, regions, '(', 'NCRs)', of, the, 'HA', and, 'NA', segments, are, 'subtype-specific,', varying, significantly, in, sequence, and, length, at, both, the, 3, '\'', and, 5, '\'', ends])]). relacion([sujeto(['Interestingly,', we]), verbo([found]), complemento([that, nucleotides, &, 'quot;CC"', at, positions, 13, -, 14, at, the, 3, '\'', end, and, &, 'quot;GUG"', at, positions, 14, '\'', -, 16, '\'', at, the, 5, '\'', end, are, absolutely, conserved, among, all, 'HA', 'subtype-specific', 'NCRs'])]). relacion([sujeto(['In', order, to, understand, the, significance, of, these, highly]), verbo([conserved]), complemento(['HA', 'segment-specific', 'NCR', nucleotides, in, the, virus, life, 'cycle,', we, performed, extensive, mutagenesis, on, the, 'HA', 'segment-specific', 'NCR', nucleotides, and, studied, their, functional, significance, in, regulating, influenza, 'A', virus, replication, in, the, context, of, the, 'HA', segment, with, both, 'RNP', reconstitution, and, virus, infection, systems])]). relacion([sujeto(['We']), verbo([found]), complemento([that, the, 'base-pairing', at, '(', 3, '\'', ')', 13, -, '(', 5, '\'', ')', 14, '\'', positions, is, critical, for, 'RNA', promoter, activity, while, the, identity, of, the, base, pair, is, critical, in, determining, 'HA', segment, packaging])]). relacion([sujeto(['Moreover,', the, identity, of, the, residue, at, '(', 3, '\'', ')', 14, is, more, functionally, important, in]), verbo([regulating]), complemento([virus, genome, packaging, than, in, regulating, viral, 'RNA', synthesis])]). relacion([sujeto(['The', 'segment-specific', complementary, nucleotides, '(', 13, -, 15, in, the, 3, '\'', end, and, 14, '\'', -, 16, '\'', in, the, 5, '\'', 'end)', in, the, extended, duplex, region, of, the, influenza, virus, 'RNA', promoter, vary, significantly, among, different, segments, and]), verbo([have]), complemento([rarely, been, studied])]). relacion([sujeto(['We', here, performed, mutagenesis, analysis, of, the, highly]), verbo([conserved]), complemento(['HA', 'segment-specific', nucleotides, in, the, extended, duplex, region, and, examined, their, effects, on, virus, replication, in, the, context, of, the, 'WSN', virus, infection])]). relacion([sujeto(['We']), verbo([found]), complemento([that, these, 'HA', 'segment-specific', 'nucleotides,', not, only, act, as, a, part, of, the, 'RNA', 'promoter,', but, also, play, a, critical, role, in, 'HA', segment, packaging])]). relacion([sujeto(['Therefore,', we, showed, 'experimentally,', for, the, first, 'time,', the, requirement, of, the, nucleotides, in, the, extended, duplex, region, for, the, 'RNA', 'promoter,', but, also, identified, specific, noncoding, residues, in]), verbo([regulating]), complemento(['HA', segment, packaging])]). relacion([sujeto(['This', work]), verbo([has]), complemento([implications, for, the, development, of, attenuated, vaccine, strains, and, for, elucidation, the, mechanisms, of, the, virus, genome, packaging])]). relacion([sujeto(['Gram-positive', bacteria, in, the, genus, 'Enterococcus', are, a, frequent]), verbo([cause]), complemento([of, 'catheter-associated', urinary, tract, infection, '(', 'CAUTI),', a, disease, whose, treatment, is, increasingly, challenged, by, 'multiantibiotic-resistant', strains])]). relacion([sujeto(['We']), verbo([have]), complemento([recently, shown, that, 'E'])]). relacion([sujeto([&, 'nbsp;faecalis', uses, the, 'Ebp', 'pilus,', a, heteropolymeric, surface, 'fiber,', to]), verbo([bind]), complemento([the, host, protein, fibrinogen, as, a, critical, step, in, 'CAUTI', pathogenesis])]). relacion([sujeto(['Fibrinogen', is, deposited, on, catheters, due, to, 'catheter-induced', inflammation, and, is]), verbo([recognized]), complemento([by, the, 'N-terminal', domain, of, 'EbpA', '(', 'EbpA(NTD)),', the, 'Ebp', 'pilus\'s', adhesin])]). relacion([sujeto(['In', a, murine, 'model,', vaccination, with, 'EbpA(NTD)']), verbo([confers]), complemento([significant, protection, against, 'CAUTI'])]). relacion([sujeto(['Here,', we, explored, the, mechanism, of, protection, using, passive, transfer, of, immune, sera, to, show, that, antisera, blocking, 'EbpA(NTD)-fibrinogen', interactions, not, only, is, prophylactic, but, also, can]), verbo([act]), complemento([therapeutically, to, reduce, bacterial, titers, of, an, existing, infection])]). relacion([sujeto(['The', results, indicate, 'that,', despite, diversity, in, levels, of, fibrinogen, 'binding,', strategies, that]), verbo([target]), complemento([the, disruption, of, 'EbpA(NTD)-fibrinogen', interactions, have, considerable, promise, for, treatment, of, 'CAUTI'])]). relacion([sujeto(['Urinary', catheterization, is, a, routine, medical, 'procedure,', and, it]), verbo([has]), complemento([been, estimated, that, 30, million, 'Foley', catheters, are, used, annually, in, the, 'United', 'States'])]). relacion([sujeto(['Additionally,', these, infections, can]), verbo([lead]), complemento([to, serious, 'complications,', including, bloodstream, infection, and, death])]). relacion([sujeto(['Enterococcus', strains, are, a, common]), verbo([cause]), complemento([of, these, 'infections,', and, management, of, enterococcal, infections, has, been, more, difficult, in, recent, years, due, to, the, development, of, antibiotic, resistance, and, the, ability, of, strains, to, 'disseminate,', resulting, in, a, major, threat, in, hospital, settings])]). relacion([sujeto(['The', bacterial, pathogen, 'Staphylococcus', aureus]), verbo([expresses]), complemento([a, variety, of, cell, surface, adhesion, proteins, that, bind, to, host, extracellular, matrix, proteins])]). relacion([sujeto(['While', it, is, well, established, that, the, 'A', region, of, 'Cna']), verbo([mediates]), complemento([ligand, 'binding,', whether, the, repetitive, 'B', region, has, a, dedicated, function, is, not, known])]). relacion([sujeto(['Here,', we]), verbo([report]), complemento([the, direct, measurement, of, the, mechanical, strength, of, 'Cna-Cn', bonds, on, living, 'bacteria,', and, we, quantify, the, antiadhesion, activity, of, monoclonal, antibodies, '(', 'MAbs)', targeting, this, interaction])]). relacion([sujeto(['The', 'B', region, is]), verbo([required]), complemento([for, strong, ligand, binding, and, has, been, found, to, function, as, a, spring, capable, of, sustaining, high, forces])]). relacion([sujeto(['This', previously, undescribed, mechanical, response, of, the, 'B', region, is, of, biological, significance, as, it]), verbo([provides]), complemento([a, means, to, project, the, 'A', region, away, from, the, bacterial, surface, and, to, maintain, bacterial, adhesion, under, conditions, of, high, forces])]). relacion([sujeto(['Some', 'MAbs', are, more, efficient, in, blocking, 'single-cell', 'adhesion,']), verbo([suggesting]), complemento([that, they, act, as, competitive, inhibitors, that, bind, 'Cna', residues, directly, involved, in, ligand, binding])]). relacion([sujeto(['This']), verbo([report]), complemento([highlights, the, role, of, protein, mechanics, in, activating, the, function, of, staphylococcal, adhesion, proteins, and, emphasizes, the, potential, of, antibodies, to, prevent, staphylococcal, adhesion, and, biofilm, formation])]). relacion([sujeto(['Cna', is, a, collagen, '(', 'Cn)-binding', protein, from, 'Staphylococcus', aureus, that, is]), verbo([involved]), complemento([in, pathogenesis])]). relacion([sujeto(['We', show, that, single, 'Cna-Cn', bonds, are, very, 'strong,', reflecting, 'high-affinity']), verbo([binding]), complemento([by, the, collagen, hug, mechanism])]). relacion([sujeto(['This', unanticipated, mechanical, 'response,', not, previously, described, for, any, staphylococcal, 'adhesin,', favors, a, model, in, which, the, 'B', region]), verbo([has]), complemento([a, mechanical, function, that, is, essential, for, strong, ligand, binding])]). relacion([sujeto(['Finally,', we, assess, the, antiadhesion, activity, of, monoclonal, antibodies, against, 'Cna,']), verbo([suggesting]), complemento([that, they, could, be, used, to, inhibit, 'S'])]). relacion([sujeto(['The', efforts, to, control, malaria, may, affect, malaria, parasite, genetic, variability, and, drug, 'resistance,', the, latter]), verbo([associated]), complemento([with, genetic, events, that, promote, mechanisms, to, escape, drug, action])]). relacion([sujeto(['The', worldwide, spread, of, drug, resistance]), verbo([has]), complemento([been, a, major, obstacle, in, controlling, 'Plasmodium', falciparum, 'malaria,', thus, the, study, of, the, origin, and, spread, of, associated, mutations, may, provide, some, insights, in, the, prevention, of, its, emergence])]). relacion([sujeto(['This', study]), verbo([reports]), complemento([the, analysis, of, 'P'])]). relacion([sujeto([falciparum, genetic, diversity, focusing, antimalarial, resistance]), verbo([associated]), complemento([molecular, markers, in, two, socioeconomically, different, villages, in, mainland, 'Equatorial', 'Guinea'])]). relacion([sujeto(['Genetic', diversity, was, assessed, by, analysis, of, 'Pfmsp2', gene, and, neutral, microsatellite, loci, 'Pfdhps', and, 'Pfdhfr', alleles]), verbo([associated]), complemento([with, 'sulphadoxine-pyrymethamine', '(', 'SP)', resistance, and, flanking, microsatellite, loci, were, investigated, and, prevalence, of, drug, resistance, associated, point, mutations, of, 'Pfcrt,', 'Pfmdr1,', 'Pfdhfr', and, 'Pfdhps', genes, was, estimated])]). relacion([sujeto(['Further,', to, monitor, the, use, of, an, 'ACT,', we]), verbo([provide]), complemento([a, baseline, prevalence, of, 'K13-propeller', mutations, and, 'Pfmdr1', copy, numbers])]). relacion([sujeto(['After', eight, 'years,', noticeable, differences, occurred, in, the, distribution, of, genotypes]), verbo([conferring]), complemento([resistance, to, chloroquine, and, 'SP', and, the, spread, of, mutated, genotypes, differed, according, the, setting])]). relacion([sujeto(['Regarding', artemisinin, 'resistance,', although, mutations]), verbo([reported]), complemento([as, linked, to, artemisinin, resistance, were, not, present, at, the, 'time,', several, 'SNPs', in, the, 'K13', gene, were, 'observed,', suggesting, that, a, closer, monitoring, should, be, maintained, to, prevent, a, possible, spread, of, 'artemisinin-resistance', in, 'Africa'])]). relacion([sujeto(['The', current, paradigm, for, the, treatment, of, chronic, hepatitis, 'C', virus, '(', 'HCV)', infection]), verbo([involves]), complemento([combinations, of, agents, which, act, directly, on, steps, of, the, 'HCV', lifecycle])]). relacion([sujeto(['Here', we]), verbo([report]), complemento([the, preclinical, characteristics, of, 'ITMN-8187,', a, 'non-macrocyclic', inhibitor, of, the, 'NS3/4A', 'HCV', protease])]). relacion([sujeto(['X-ray', crystallographic, studies, of, 'ITMN-8187', and, simeprevir]), verbo([binding]), complemento([to, 'NS3/4A', protease, demonstrated, good, agreement, between, structures])]). relacion([sujeto(['Low', nanomolar, biochemical, potency, was]), verbo([maintained]), complemento([against, 'NS3/4A', derived, from, 'HCV', genotypes, 1, ',', 2, 'b,', 4, ',', 5, ',', and, 6])]). relacion([sujeto(['Here', we]), verbo([report]), complemento([a, 'cell-biological', study, in, model, organisms, of, the, genus, 'Streptomyces,', which, are, 'Actinobacteria', that, grow, in, a, highly, polarized, fashion, to, form, branching, hyphae])]). relacion([sujeto(['The', characteristic, apical, growth, of, 'Streptomyces', hyphae, is, orchestrated, by, protein, 'assemblies,', called, 'polarisomes,', that, contain, 'coiled-coil', proteins, 'DivIVA', and, 'Scy,', and]), verbo([recruit]), complemento([cell, wall, synthesis, complexes, and, the, 'stress-bearing', cytoskeleton, of, 'FilP', to, the, tip, regions, of, the, hyphae])]). relacion([sujeto(['Hyperosmotic', shock]), verbo([caused]), complemento([arrest, of, 'growth,', loss, of, 'turgor,', and, hypercondensation, of, chromosomes])]). relacion([sujeto(['Instead,', cell, polarity, was, reprogrammed, and, polarisomes, were, redistributed, to, new, 'sites,']), verbo([leading]), complemento([to, emergence, of, multiple, lateral, branches, from, which, growth, occurred])]). relacion([sujeto(['Factors', known, to]), verbo([regulate]), complemento([the, branching, pattern, of, 'Streptomyces', 'hyphae,', such, as, the, 'serine/threonine', kinase, 'AfsK', and, 'Scy,', were, not, involved, in, reprogramming, of, cell, 'polarity,', indicating, that, different, mechanisms, may, act, in, different, environmental, conditions, to, control, hyphal, branching])]). relacion([sujeto(['Our', observations, of, hyphal, morphology, during, the, stress, response, indicate, that, turgor, and, sufficient, hydration, of, cytoplasm, are]), verbo([required]), complemento([for, 'Streptomyces', tip, growth])]). relacion([sujeto(['We']), verbo([report]), complemento([here, that, severe, 'hyper-osmotic', stress, causes, cessation, of, 'growth,', followed, by, reprogramming, of, cell, polarity, and, rearrangement, of, growth, zones, to, promote, lateral, hyphal, branching])]). relacion([sujeto(['Besides', canonical, hedgehog, signalling, with, smoothened, '(', 'SMO)-dependent', activation, of, 'GLI', transcription, 'factors,', 'GLI', can, be]), verbo([activated]), complemento([independently, of, classical, hedgehog, ligands, and, receptors, '(', 'so-called', 'non-canonical', 'pathways)'])]). relacion([sujeto(['Here,', we, aimed, to, evaluate, the, role, of, 'non-canonical', hedgehog, signalling, in, 'SSc', and, to, test, the, efficacy, of, direct, 'GLI', inhibitors, that]), verbo([target]), complemento([simultaneously, canonical, and, 'non-canonical', hedgehog, pathways])]). relacion([sujeto(['The', 'GLI', inhibitor, 'GANT-61', was, used, to]), verbo([inhibit]), complemento([canonical, as, well, as, 'non-canonical', hedgehog, 'signalling,', while, the, 'SMO', inhibitor, vismodegib, was, used, to, selectively, target, canonical, hedgehog, signalling])]). relacion([sujeto(['TGF-β', upregulated, 'GLI2', in, a, 'Smad3-dependent', manner, and]), verbo([induced]), complemento([nuclear, accumulation, and, 'DNA', binding, of, 'GLI2'])]). relacion([sujeto(['Combined']), verbo([targeting]), complemento([of, canonical, and, 'non-canonical', hedgehog, signalling, with, direct, 'GLI', inhibitors, exerted, more, potent, antifibrotic, effects, than, selective, targeting, of, canonical, hedgehog, signalling, with, 'SMO', inhibitors, in, experimental, dermal, and, pulmonary, fibrosis])]). relacion([sujeto(['Our', data, demonstrate, that, hedgehog, pathways, and, 'TGF-β', signalling, both, converge, to, 'GLI2', and, that, 'GLI2', integrates, those, signalling, to]), verbo([promote]), complemento([tissue, fibrosis])]). relacion([sujeto(['These', findings, may]), verbo([have]), complemento([translational, implications, as, 'non-selective', inhibitors, of, 'GLI2', are, in, clinical, use, and, selective, molecules, are, currently, in, development])]). relacion([sujeto(['To', better, understand, the, genus, 'Lepilemur,', we, analyzed, 35, complete, mitochondrial, genomes, representing, all]), verbo([recognized]), complemento([26, sportive, lemur, taxa, and, estimated, divergence, dates])]). relacion([sujeto(['We', estimated, the, initial, split, between, the, eastern, and, western, 'Lepilemur', clades, to]), verbo([have]), complemento([occurred, in, the, 'Miocene'])]). relacion([sujeto(['In', order, to, characterize, the, functionality, of, the, immunologic, response, to, 'ACT', after, 'infection,', we]), verbo([have]), complemento([developed, an, assay, for, testing, the, ability, of, serum, samples, from, subjects, infected, with, 'B'])]). relacion([sujeto(['In', most, 'cases,', a, 'RAM', domain, fuses, with, a, 'DNA-binding', domain, to]), verbo([act]), complemento([as, a, transcriptional, regulator])]). relacion([sujeto(['Therefore,', we, hypothesized, that, 'SraA,', which, senses, amino, acids, through, its, 'RAM', 'domain,', may]), verbo([interact]), complemento([with, other, proteins, to, modify, its, functions])]). relacion([sujeto(['In', the, present, 'study,', we, identified, anthranilate, phosphoribosyltransferase, '(', 'AnPRT),', the, second, enzyme, in, the, tryptophan, biosynthetic, 'pathway,', as, a, partner, protein, that]), verbo([interacted]), complemento([with, 'SraA', in, 'T'])]). relacion([sujeto(['An', enzyme, assay, revealed, that, 'AnPRT', was, only]), verbo([inhibited]), complemento([by, tryptophan, in, the, presence, of, 'SraA'])]). relacion([sujeto(['This', result]), verbo([suggests]), complemento([a, novel, feedback, control, mechanism, for, tryptophan, biosynthesis, through, an, 'inter-RAM', domain, interaction, in, bacteria])]). relacion([sujeto(['Rupture', of, endosomes, and, lysosomes, is, a, major, cellular, stress, condition]), verbo([leading]), complemento([to, cell, death, and, degeneration])]). relacion([sujeto(['Together,', they]), verbo([act]), complemento([downstream, of, 'K63-linked', ubiquitination, and, p62, 'recruitment,', and, selectively, remove, 'K48-linked', ubiquitin, conjugates, from, a, subpopulation, of, damaged, lysosomes, to, promote, autophagosome, formation])]). relacion([sujeto(['Lysosomal', clearance, is, also, compromised, in, 'MEFs', harboring, a, p97, mutation, that]), verbo([causes]), complemento([inclusion, body, myopathy, and, 'neurodegeneration,', and, damaged, lysosomes, accumulate, in, affected, patient, tissue, carrying, the, mutation])]). relacion([sujeto(['Thus,', our, data]), verbo([reveal]), complemento([an, important, mechanism, of, how, p97, maintains, lysosomal, 'homeostasis,', and, implicate, the, pathway, as, a, modulator, of, degenerative, diseases])]). relacion([sujeto(['Fc-gamma', receptors, '(', 'FCGRs)', are]), verbo([expressed]), complemento([on, immune, 'cells,', bind, to, 'antibodies,', and, trigger, 'antibody-induced', 'cell-mediated', 'anti-tumor', responses, when, 'tumor-reactive', antibodies, are, present])]). relacion([sujeto(['Prior', studies, of, cancer, patients, treated, with, immunotherapy, indicate, that, 'FCGR', polymorphisms, can, influence, antitumor, response, for, certain, immunotherapies, that]), verbo([act]), complemento([via, therapeutically, administered, mAbs, or, via, endogenous, 'tumor-reactive', antibodies, induced, from, tumor, antigen, vaccines])]). relacion([sujeto(['We', evaluated, the, patients, in, this, 'SELECT', trial, to, determine, whether, higher, affinity, 'FCGR', polymorphisms, are]), verbo([associated]), complemento([with, outcome])]). relacion([sujeto(['When', higher, affinity, genotypes, for, 'FCGR2A,', 'FCGR3A', and, 'FCGR2C', were, considered, 'together,', they, were]), verbo([associated]), complemento([with, significantly, increased, tumor, shrinkage, and, prolonged, survival, in, response, to, 'HD-IL2'])]). relacion([sujeto(['While', associations, of, higher, affinity, 'FCGR', genotype, with, clinical, outcome]), verbo([have]), complemento([been, demonstrated, with, mAb, therapy, and, with, idiotype, 'vaccines,', to, our, 'knowledge,', this, is, the, first, study, to, show, associations, of, 'FCGR', genotypes, with, outcome, following, 'HD-IL2', treatment])]). relacion([sujeto(['We', hypothesize, that, endogenous, 'anti-tumor', antibodies, may, engage, immune, cells, through, their, 'FCGRs,', and, 'HD-IL2', may]), verbo([enhance]), complemento(['antibody-induced', tumor, 'destruction,', or, 'antibody-enhanced', tumor, antigen, 'presentation,', via, augmented, activation, of, innate, or, adaptive, immune, 'responses;', this, 'FCGR-mediated', immune, activity, would, be, augmented, through, immunologically, favorable, 'FCGRs'])]). relacion([sujeto(['We', employed, a, 'system-level', in, vivo, chemoproteomic, profiling, approach, to, explore, the, cellular, dynamics, of, protein, thiol, redox, and, how, thiol, redox]), verbo([mediates]), complemento([the, function, of, the, dinitrogenase, 'NifHDK,', an, enzyme, complex, capable, of, aerobic, hydrogenase, activity])]). relacion([sujeto(['We']), verbo([found]), complemento([that, 'NifHDK', responds, to, intracellular, redox, conditions, and, may, act, as, an, emergency, electron, valve, to, prevent, harmful, reactive, oxygen, species, formation, in, concert, with, other, cell, strategies, for, maintaining, redox, homeostasis])]). relacion([sujeto(['These', results]), verbo([provide]), complemento([new, insight, into, cellular, redox, dynamics, useful, for, advancing, photolytic, bioenergy, technology, and, reveal, a, new, understanding, for, the, biological, function, of, 'NifHDK'])]). relacion([sujeto(['Here,', we, demonstrate, that, high, levels, of, hydrogen, synthesis, can, be]), verbo([induced]), complemento([as, a, protection, mechanism, against, oxidative, stress, via, the, dinitrogenase, enzyme, complex, in, 'Cyanothece', sp])]). relacion([sujeto(['We', utilized, a, chemoproteomic, approach, to, capture, the, in, situ, dynamics, of, reductant, partitioning, within, the, 'cell,']), verbo([revealed]), complemento([proteins, and, reactive, thiols, that, may, be, involved, in, redox, sensing, and, signaling])]). relacion([sujeto(['Campylobacter', is, the]), verbo([leading]), complemento([cause, of, human, gastroenteritis, worldwide])]). relacion([sujeto(['Wild', 'birds,', including, 'American', 'crows,', are, abundant, in, 'urban,', 'suburban,', and, agricultural, settings, and, are, likely, zoonotic, vectors, of, 'Campylobacter', 'Their', proximity, to, humans, and, livestock]), verbo([increases]), complemento([the, potential, spreading, of, 'Campylobacter', via, crows, between, the, 'environment,', 'livestock,', and, humans])]). relacion([sujeto(['However,', no, studies]), verbo([have]), complemento([definitively, demonstrated, that, crows, are, a, vector, for, pathogenic, 'Campylobacter', 'We', used, genomics, to, evaluate, the, zoonotic, and, pathogenic, potential, of, 'Campylobacter', from, crows, to, other, animals, with, 184, isolates, obtained, from, 'crows,', 'chickens,', 'cows,', 'sheep,', 'goats,', 'humans,', and, nonhuman, primates])]). relacion([sujeto(['Whole-genome', analysis, uncovered, two, distinct, clades, of, 'Campylobacter', jejuni, 'genotypes;', the, first, contained, genotypes]), verbo([found]), complemento([only, in, 'crows,', while, a, second, genotype, contained, &, 'quot;generalist"', genomes, that, were, isolated, from, multiple, host, 'species,', including, isolates, implicated, in, human, 'disease,', primate, 'gastroenteritis,', and, livestock, abortion])]). relacion([sujeto(['Two', major, 'β-lactamase', genes, were, observed, frequently, in, these, genomes, '(', 'oxa-184,', 55, '%', ',', and, 'oxa-61,', 29, '%', ')', ',', where, 'oxa-184', was]), verbo([associated]), complemento([only, with, crows, and, 'oxa-61', was, associated, with, generalists])]). relacion([sujeto(['A', specific, cdtC, allele, was]), verbo([associated]), complemento([with, abortion, in, livestock, and, was, concomitant, with, tetO, 'These', findings, indicate, that, crows, harboring, a, generalist, 'C'])]). relacion([sujeto([jejuni, genotype, may]), verbo([act]), complemento([as, a, vector, for, the, zoonotic, transmission, of, 'Campylobacter', 'IMPORTANCE:', 'This', study, examined, the, link, between, public, health, and, the, genomic, variation, of, 'Campylobacter', in, relation, to, disease, in, 'humans,', 'primates,', and, livestock])]). relacion([sujeto(['Use', of, 'large-scale', 'whole-genome', sequencing, enabled, 'population-level', assessment, to]), verbo([find]), complemento([new, genes, that, are, linked, to, livestock, disease])]). relacion([sujeto(['Most', 'double-stranded', 'RNA', '(', 'dsRNA)', viruses, are]), verbo([transcribed]), complemento([and, replicated, in, a, specialized, icosahedral, capsid, with, a, 'T=1', lattice, consisting, of, 60, asymmetric, capsid, protein, '(', 'CP)', dimers])]). relacion([sujeto(['They', also]), verbo([act]), complemento([as, molecular, sieves, that, isolate, the, virus, genome, from, host, defense, mechanisms, and, allow, the, passage, of, nucleotides, and, viral, transcripts])]). relacion([sujeto(['RnQV1']), verbo([has]), complemento([a, quadripartite, 'genome,', and, the, capsid, is, based, on, a, 'single-shelled', 'T=1', lattice, built, of, 'P2-P4', dimers])]). relacion([sujeto(['Whereas', the, 'RnQV1-W1118', capsid, is, built, of, 'full-length', 'CP,', 'P2', and, 'P4', of, 'RnQV1-W1075', are, cleaved, into, several, 'polypeptides,']), verbo([maintaining]), complemento([the, capsid, structural, organization])]). relacion([sujeto(['RnQV1', heterodimers]), verbo([have]), complemento([a, quaternary, organization, similar, to, that, of, homodimers, of, reoviruses, and, other, dsRNA, mycoviruses])]). relacion([sujeto(['The', 'RnQV1', capsid, is, the, first, 'T=1', capsid, with, a, heterodimer, as, an, asymmetric, unit]), verbo([reported]), complemento([to, date, and, follows, the, architectural, principle, for, dsRNA, viruses, that, a, 120, -, subunit, capsid, is, a, conserved, assembly, that, supports, dsRNA, replication, and, organization])]). relacion([sujeto(['Given', their, importance, to, 'health,', members, of, the, family, 'Reoviridae', are, the, basis, of, most, structural, and, functional, studies, and]), verbo([provide]), complemento([much, of, our, knowledge, of, dsRNA, viruses])]). relacion([sujeto(['Analysis', of, 'bacterial,', 'protozoal,', and, fungal, dsRNA, viruses]), verbo([has]), complemento([improved, our, understanding, of, their, 'structure,', 'function,', and, 'evolution,', as, well])]). relacion([sujeto(['Type', 'I', 'IFN', transcriptionally]), verbo([induces]), complemento([a, large, number, of, cellular, 'genes,', collectively, known, as, 'IFN-stimulated', gene, '(', 'ISG)', 'proteins,', which, act, as, antivirals])]). relacion([sujeto(['In', this, 'study,', we]), verbo([have]), complemento([interrogated, 'IFIT', proteins, for, the, ability, to, inhibit, the, growth, of, human, parainfluenza, virus, type, 3, '(', 'PIV3),', a, nonsegmented, 'negative-strand', 'RNA', virus, of, the, 'Paramyxoviridae', family, and, a, major, cause, of, respiratory, disease, in, children])]). relacion([sujeto(['We']), verbo([found]), complemento([that, 'IFIT1', significantly, inhibited, 'PIV3,', whereas, 'IFIT2,', 'IFIT3,', and, 'IFIT5', were, less, effective, or, not, at, all])]). relacion([sujeto(['In', further, screening, a, set, of, 'ISG', proteins, we, discovered, that, several, other, such, proteins, also]), verbo([inhibited]), complemento(['PIV3,', including, 'IFITM1,', 'IDO', '(', indoleamine, 2, ',', 3, -, 'dioxygenase),', 'PKR', '(', protein, 'kinase,', 'RNA', 'activated),', and, viperin, '(', virus, inhibitory, 'protein,', endoplasmic, reticulum, 'associated,', interferon, 'inducible)/Cig5'])]). relacion([sujeto(['These', results, advance, our, knowledge, of, diverse, 'ISG', proteins, functioning, as, antivirals, and, may]), verbo([provide]), complemento([novel, approaches, against, 'PIV3'])]). relacion([sujeto(['IFN']), verbo([inhibits]), complemento([virus, growth, by, inducing, a, large, number, of, 'IFN-stimulated', gene, '(', 'ISG)', 'proteins,', several, of, which, have, been, shown, to, have, specific, antiviral, functions])]). relacion([sujeto(['In', this, 'article,', we]), verbo([report]), complemento([several, 'ISG', proteins, that, strongly, inhibit, 'PIV3', 'growth,', the, use, of, which, may, allow, a, better, antiviral, regimen, targeting, 'PIV3'])]). relacion([sujeto(['It', was, hypothesized, that, smokers, assigned, to, a, 'CHW', 'face-to-face', condition, would]), verbo([have]), complemento([higher, abstinence, at, 12, -, month, posttreatment, than, smokers, enrolled, in, 'CHW', referral, to, a, 'state-sponsored', quitline, condition])]). relacion([sujeto(['Intrapersonal', and, 'treatment-related', factors]), verbo([associated]), complemento([with, abstinence, at, 12, months, were, determined])]). relacion([sujeto(['Age,', marital, 'status,', and, baseline, levels, of, cigarette, 'consumption,', depressive, 'symptoms,', and, 'self-efficacy', for, quitting, in, positive, settings, were]), verbo([associated]), complemento([with, 'abstinence,', as, was, counseling, dose, during, treatment])]). relacion([sujeto(['In', the, last, 'decade,', important, advances]), verbo([have]), complemento([been, made, in, regard, to, 'endogenous,', and, therefore, 'non-infectious,', initiators, of, 'inflammation,', which, can, act, through, the, same, receptors, as, pathogens])]). relacion([sujeto(['These', molecules, are, referred, to, as, 'damage-associated', molecular, patterns, '(', 'DAMPs),', and, their, involvement, in, reproduction]), verbo([has]), complemento([only, recently, been, unraveled])]). relacion([sujeto(['Even', though, inflammation, is, necessary, for, successful, 'reproduction,', untimely, activation, of, inflammatory, processes, can]), verbo([have]), complemento([devastating, effect, on, pregnancy, outcomes])]). relacion([sujeto(['Many', 'DAMPs,', such, as, uric, 'acid,', 'high-mobility', group, box, 1, '(', 'HMGB1),', interleukin, '(', 'IL)-1', and, 'cell-free', fetal, 'DNA,']), verbo([have]), complemento([been, associated, with, pregnancy, 'complications,', such, as, 'miscarriages,', preeclampsia, and, preterm, birth, in, preclinical, models, and, in, humans])]). relacion([sujeto(['Genome-wide', association, studies, '(', 'GWAS)']), verbo([have]), complemento([identified, markers, within, the, 'WNT4', region, on, chromosome, 1, p36])]). relacion([sujeto([12, showing, consistent, and, strong, association, with]), verbo([increasing]), complemento([endometriosis, risk])]). relacion([sujeto(['Fine', mapping, using, sequence, and, imputed, genotype, data]), verbo([has]), complemento([revealed, strong, candidates, for, the, causal, 'SNPs', within, these, critical, 'regions;', 'however,', the, molecular, pathogenesis, of, these, 'SNPs', is, currently, unknown])]). relacion([sujeto(['SNP', rs3820282, is, a, significant, eQTL, in, whole, blood]), verbo([decreasing]), complemento([expression, of, 'LINC00339', '(', also, known, as, 'HSPC157)', and, increasing, expression, of, 'CDC42', '(', 'P', =, 2.0, '×10(-54)', and, 4.5, 'x10(-4)', 'respectively)'])]). relacion([sujeto(['There', was, no, evidence, for, eQTL, effects, for, 'WNT4', 'Chromatin', conformation, capture]), verbo([provides]), complemento([evidence, for, risk, 'SNPs', interacting, with, the, promoters, of, both, 'LINC00339', and, 'CDC4', and, luciferase, reporter, assays, suggest, the, risk, 'SNP', rs12038474, is, located, in, a, transcriptional, silencer, for, 'CDC42', and, the, risk, allele, increases, expression, of, 'CDC42'])]). relacion([sujeto(['Taken', 'together,', our, results]), verbo([suggest]), complemento([that, 'SNPs', increasing, endometriosis, risk, in, this, region, act, through, 'CDC42,', but, further, functional, studies, are, required, to, rule, out, inverse, regulation, of, both, 'LINC00339', and, 'CDC42'])]). relacion([sujeto(['Activin', 'A', is, one, of, the, members, of, transforming, growth, 'factor-β', superfamily, that, is]), verbo([expressed]), complemento([in, human, large, luteal, 'cells,', and, may, act, in, an, 'autocrine/paracrine', manner, to, regulate, luteal, function])]). relacion([sujeto(['To', 'date,', whether, activin, 'A', can]), verbo([induce]), complemento([the, expression, of, 'PTGS2', and, the, production, of, 'PGE2', in, human, 'granulosa-lutein', cells, is, largely, unknown])]). relacion([sujeto(['We']), verbo([have]), complemento([demonstrated, that, activin, 'A', upregulated, the, expression, of, 'PTGS2', and, increased, the, production, of, 'PGE2', via, an, 'ACVR1B-mediated', 'SMAD2/3-SMAD4', signaling, pathway])]). relacion([sujeto(['Our', results]), verbo([suggest]), complemento([that, activin, 'A', may, be, involved, in, the, modulation, of, human, corpus, luteum, formation, via, the, induction, of, 'PTGS2', expression, and, 'PGE2', production])]). relacion([sujeto(['The', structures, of, all, the, compounds]), verbo([have]), complemento([been, discussed, on, the, basis, of, elemental, 'analysis,', 'FT-IR,', 'NMR,', 'UV-Visible,', 'ESI-Mass,', 'TGA,', 'ESR,', 'SEM,', powder, 'XRD', and, magnetic, moments])]). relacion([sujeto(['Based', on, the, analytical, and, spectral, data, a, square, planar, geometry]), verbo([has]), complemento([been, assigned, to, all, complexes, in, which, the, 'Schiff', bases, act, as, monobasic, bidentate, 'ligands,', coordinating, through, the, azomethine, nitrogen, and, phenolic, oxygen, atom])]). relacion([sujeto(['DNA']), verbo([binding]), complemento([ability, of, these, complexes, was, studied, on, 'CT-DNA', by, using, 'UV-Vis', 'absorption,', fluorescence, and, viscometry])]). relacion([sujeto(['All', the, 'DNA']), verbo([binding]), complemento([studies, reveal, that, they, are, good, intercalators])]). relacion([sujeto(['The', potential, importance, of, cytoplasmic, incompatibility, '(', 'CI)-inducing', bacterial, symbionts, in, speciation, of, their, arthropod, hosts]), verbo([has]), complemento([been, debated])]). relacion([sujeto(['Theoretical', advances]), verbo([have]), complemento([led, to, a, consensus, that, a, role, is, plausible, when, 'CI', is, combined, with, other, isolating, barriers])]). relacion([sujeto(['Thus,', asymmetrical, hybrid, incompatibilities, and, 'CI']), verbo([act]), complemento([as, complementary, isolating, mechanisms])]). relacion([sujeto(['Copper(I)', complexes, of, the, formula, '[', 'Cu(L)(PPh3)2]X', '(', 1, -, 4, ')', '(', 'X = Cl(1),', 'ClO4(2),', 'BF4(3)', and, 'PF6(4))', '[', where, 'L = N-(2-{[(2E)-2-(4-nitrobenzylidenyl)hydrazinyl]carbonyl}phenyl)benzamide;', 'PPh3 = triphenylphosphine]']), verbo([have]), complemento([been, prepared, by, the, condensation, of, 'N-[2-(hydrazinocarbonyl)phenyl]benzamide', with, 4, -, nitrobenzaldehyde, followed, by, the, reaction, with, 'CuCl,', '[', 'Cu(MeCN)4]ClO4,', '[', 'Cu(MeCN)4]BF4', and, '[', 'Cu(MeCN)4]PF6', in, presence, of, triphenylphosphine, as, a, coligand])]). relacion([sujeto(['A', single, crystal, 'X-ray', diffraction, study, of, the, representative, complex, '[', '(', 'Cu(L)(PPh3)2]CIO4', '(', 2, ')']), verbo([reveals]), complemento([a, distorted, tetrahedral, geometry, around, 'Cu(I)'])]). relacion([sujeto(['Significant']), verbo([increase]), complemento([in, size, of, the, counter, anion, shows, marked, effect, on, quantum, efficiency, and, lifetime, of, the, complexes, in, solution])]). relacion([sujeto(['DNA', can, be, programmed, to, assemble, into, a, variety, of, shapes, and, patterns, on, the, nanoscale, and, can]), verbo([act]), complemento([as, a, template, for, hybrid, nanostructures, such, as, conducting, 'wires,', protein, arrays, and, 'field-effect', transistors])]). relacion([sujeto(['This', system, is, inherently, adept, at, solving, probabilistic, problems, and, was, used, to]), verbo([find]), complemento([the, possible, paths, through, a, maze, and, to, evaluate, stochastic, switching, circuits])]). relacion([sujeto(['Lung', exposure, to, airborne, and, food, 'contaminants,', such, as, 'PCBs,', may]), verbo([cause]), complemento([possible, lung, 'disorders,', such, as, cancer])]). relacion([sujeto(['Noncoplanar', 'PCB40', and, coplanar, 'PCB77']), verbo([induced]), complemento([23, and, 45, '%', cytotoxicity, at, higher, concentrations, than, the, control])]). relacion([sujeto(['The', flow, cytometry, analysis, showed, that, exposure, to, 'PCB40']), verbo([caused]), complemento([a, significant, increase, in, time, spent, in, the, 'G1', phase, but, decreased, length, of, the, 'S', phase, in, a, 'concentration-', and, 'time-dependent', 'manner,', whereas, 'PCB77', exposure, decreased, time, spent, in, the, 'G1', and, 'S', phases, but, increased, time, spent, in, the, 'G2', phase])]). relacion([sujeto(['Western', blot, analysis, indicated, that, 'PCB77']), verbo([increased]), complemento([the, expression, of, cyclin, 'E,', 'CDK2,', 'p21,', and, 'caspase-9,', while, 'PCB40', decreased, the, expression, of, these, proteins, '(', except, 'CDK2', and, 'p21)'])]). relacion([sujeto(['An']), verbo([increase]), complemento([in, 'CDK', expression, after, exposure, to, 'PCB77', suggests, that, it, may, cause, carcinogenic, effects, on, 'HELF', cells, at, higher, doses])]). relacion([sujeto(['Our', results, also, demonstrate, that, the, different, cytotoxic, effects]), verbo([induced]), complemento([by, coplanar, and, nonplanar, 'PCBs', were, correlated, with, their, structural, 'characteristics;', the, coplanar, congener, was, more, cytotoxic, than, the, nonplanar, congener])]). relacion([sujeto(['The', study, elaborates, threshold, levels, for, these, chemicals, and]), verbo([suggests]), complemento([that, the, cytotoxicity, mechanisms, by, which, 'PCB', congeners, act, on, 'HELF', cells, depend, on, their, planarity, and, chemical, structures])]). relacion([sujeto(['Influenza', 'A', virus, '(', 'IAV)', is, an, important, pathogen, that]), verbo([has]), complemento([a, wide, range, of, hosts, and, represents, a, threat, to, the, health, of, humans, and, several, animal, species])]). relacion([sujeto(['IAV', infection, can]), verbo([induce]), complemento([the, transcription, of, many, genes, in, the, host])]). relacion([sujeto(['In', the, present, 'study,', we, demonstrated, for, the, first, time, that, three, different, strains, of, 'H1N1', 'IAV']), verbo([induce]), complemento([the, expression, of, an, 'IFN-stimulated', 'gene,', 'ISG20'])]). relacion([sujeto(['We', determined, the, antiviral, activity, of, 'ISG20', against, 'IAV', because, 'ISG20']), verbo([inhibited]), complemento([viral, protein, expression, and, reduced, the, progeny, viral, titer, dependent, upon, its, exonuclease, activity])]). relacion([sujeto(['To', elucidate, the, detailed, mechanism, of, 'ISG20,', we, further, demonstrated, that, 'ISG20', impairs, the, polymerase, activity, and]), verbo([inhibits]), complemento([both, the, replication, and, transcription, levels, of, the, 'M1', and, 'NP', genes])]). relacion([sujeto(['Notably,', we, identified, that, 'ISG20', colocalizes, and]), verbo([interacts]), complemento([with, 'NP', during, 'IAV', 'infection,', while, 'exonuclease-inactive', mutant, 'ISG20', lacked, association, with, 'NP,', indicating, that, 'ISG20', inhibits, 'IAV', replication, by, interacting, with, 'NP'])]). relacion([sujeto(['Together,', these, data]), verbo([provide]), complemento([a, detailed, explanation, for, the, specific, antiviral, action, of, 'ISG20', and, suggest, that, 'ISG20', may, act, as, a, promising, antiviral, drug, candidate, against, 'IAV'])]). relacion([sujeto(['Type', 2, innate, lymphoid, cells, '(', 'ILC2s)']), verbo([have]), complemento([been, shown, to, produce, large, amounts, of, type, 2, cytokines, in, a, 'non-antigen-specific', manner])]). relacion([sujeto(['These', cytokines]), verbo([act]), complemento([upstream, and, downstream, of, 'ILC2', and, are, increasingly, common, in, asthma, drug, 'development,', thus, warranting, a, closer, investigation, of, the, 'mechanism-related', clinical, manifestations, of, 'ILC2', in, the, selection, of, patients, with, asthma])]). relacion([sujeto(['Frequencies', of, 'ILC2s', were]), verbo([increased]), complemento([dramatically, in, those, with, asthma, '(', 0.04, ±, 0.02, '%', ')', compared, with, healthy, donors, '(', 0.025, ±, 0.011, '%', ')'])]). relacion([sujeto(['The', fiduciary, nature, of, the, 'patient-physician', relationship]), verbo([requires]), complemento([clinicians, to, act, in, the, best, interest, of, their, patients])]). relacion([sujeto(['In', some, 'instances,', the, 'patients\'', refusal, may, jeopardize, their, health, or, life, but, also, compromise, the, 'clinician\'s', moral, responsibility, to]), verbo([promote]), complemento([the, 'patient\'s', best, interests])]). relacion([sujeto(['In', other, 'words,', health, professionals]), verbo([have]), complemento([to, deal, with, patients, whose, behavior, and, healthcare, decisions, seem, counterproductive, for, their, 'health,', or, even, deteriorate, 'it,', because, of, lack, of, 'knowledge,', bad, habits, or, bias, without, being, the, 'patients\'', free, voluntary, choice])]). relacion([sujeto(['The', moral, dilemma, centers, on, issues, surrounding, the, limits, of, the, 'patient\'s', autonomy, '(', 'rights)', and, the, 'clinician\'s', role, to]), verbo([promote]), complemento([the, 'well-being', of, the, patient, '(', 'duties)'])]). relacion([sujeto(['In', this, paper, we, argue, that, '(', 1, ')', the, use, of, manipulative, 'strategies,', albeit, considered, 'beneficent,', defeats, the, purpose, of, patient, education, and, therefore, should, be, 'rejected;', and, '(', 2, ')', the, appropriate, strategy, is, to, empower, patients, through, patient, education, which]), verbo([enhances]), complemento([their, autonomy, and, encourages, them, to, become, full, healthcare, partners, as, opposed, to, objects, of, clinical, intervention, or, entities, whose, values, or, attitudes, need, to, be, shaped, and, changed, through, education])]). relacion([sujeto(['First,', we]), verbo([provide]), complemento([a, working, definition, of, the, concept, of, patient, education, and, a, brief, historical, overview, of, its, origin])]). relacion([sujeto(['Third,', we, argue, that, patient, education, should]), verbo([promote]), complemento(['self-rebiasing,', enhance, 'autonomy,', and, empower, patients, to, determine, their, therapeutic, goals])]). relacion([sujeto(['Mitogen-activated', protein, kinases, '(', 'MAPKs)', are]), verbo([expressed]), complemento([in, postmitotic, neurons, and, act, as, important, regulators, in, intracellular, signaling])]). relacion([sujeto(['In', addition, to, their]), verbo([nuclear]), complemento([distribution, and, roles, in, regulating, gene, 'expression,', 'MAPKs,', especially, the, extracellular, 'signal-regulated', kinase, '(', 'ERK)', 'subclass,', reside, in, peripheral, dendritic, spines, and, 'synapses,', including, the, postsynaptic, density, '(', 'PSD)', microdomain])]). relacion([sujeto(['Active', 'MAPKs', directly]), verbo([interact]), complemento([with, and, phosphorylate, local, substrates, to, alter, their, trafficking, and, 'subcellular/subsynaptic', 'distributions,', through, which, 'MAPKs', regulate, function, of, substrates, and, contribute, to, 'long-lasting', synaptic, plasticity])]). relacion([sujeto(['A', number, of, physiologically, relevant, substrates, of, 'MAPKs']), verbo([have]), complemento([been, identified, at, synaptic, sites])]). relacion([sujeto(['Through', a, reversible, phosphorylation, 'event,', 'MAPKs', rapidly, and, efficiently]), verbo([modulate]), complemento([the, function, of, these, substrates, and, thus, determine, the, strength, of, synaptic, transmission])]). relacion([sujeto(['This', review, summarizes, the, recent, progress, in, cell, biology, of, synaptic, 'MAPKs', and, analyzes, roles, of, this, specific, pool, of, 'MAPKs', in]), verbo([regulating]), complemento([local, substrates, and, synaptic, plasticity])]). relacion([sujeto(['Oxidative', stress]), verbo([causes]), complemento([cellular, damage, by, '(', 'i)', altering, protein, 'stability,', '(', 'ii)', impairing, organelle, 'function,', or, '(', 'iii)', triggering, the, formation, of, 4, -, 'HNE', protein, aggregates])]). relacion([sujeto(['Therefore,', autophagy, might]), verbo([act]), complemento([as, a, cytoprotective, response, by, removing, impaired, organelles, and, aggregated, proteins])]). relacion([sujeto(['Rotenone']), verbo([induced]), complemento([an, overproduction, of, reactive, oxygen, species, '(', 'ROS),', which, led, to, an, accumulation, of, 4, -, 'HNE', 'inclusions,', and, an, increase, in, the, number, of, autophagosomes])]). relacion([sujeto(['In', compliance, with, 'this,', rotenone, treatment]), verbo([induced]), complemento([an, increase, in, 'LC3-II', while, upstream, autophagy, markers, such, as, 'Beclin-', 1, ',', 'Vsp34', or, 'Atg5-Atg12,', were, decreased])]). relacion([sujeto(['Rotenone', reduced, the, 'autophagosome-to-lysosome', fusion, step, by]), verbo([increasing]), complemento([tubulin, acetylation, levels, through, a, 'ROS-mediated', pathway])]). relacion([sujeto(['Proof', of, this, is, the]), verbo([finding]), complemento([that, the, free, radical, 'scavenger,', 'N-acetylcysteine,', restored, autophagy, flux, and, reduced, 'rotenone-induced', tubulin, hyperacetylation])]). relacion([sujeto(['Indeed,', this, dysfunctional, autophagic, response, exacerbates, cell, death]), verbo([triggered]), complemento([by, 'rotenone,', since, 3, -, 'methyladenine,', an, autophagy, 'inhibitor,', reduced, cell, 'mortality,', while, 'rapamycin,', an, inductor, of, 'autophagy,', caused, opposite, effects])]). relacion([sujeto(['In', 'summary,', we, shed, new, light, on, the, mechanisms]), verbo([involved]), complemento([in, the, autophagic, responses, disrupted, by, oxidative, 'stress,', which, take, place, in, neurodegenerative, diseases, such, as, 'Huntington or', 'Parkinson diseases,', and, 'age-related', macular, degeneration])]). relacion([sujeto(['c-Jun', 'N-terminal', kinases, '(', 'JNKs),', which, belong, to, a, 'mitogen-activated', protein, kinase, '(', 'MAPK)', 'family,', are]), verbo([involved]), complemento([in, the, regulation, of, several, physiological, functions, in, mammals, and, act, as, mediators, of, 'apoptosis,', 'obesity,', and, memory, storage, in, the, 'brain,', including, the, processes, of, neuronal, 'de-', and, regeneration])]). relacion([sujeto(['JNK1', deficiency, resulted, in, reduced, 'BACE1', 'expression,']), verbo([suggesting]), complemento([alterations, in, amyloidogenic, pathway])]). relacion([sujeto(['In', 'addition,', protein, levels, of, 'PPAR', gamma, 'coactivator-1α', '(', 'PGC-1α),', a, molecule]), verbo([involved]), complemento([in, mitochondrial, biogenesis, and, energy, 'homeostasis,', were, decreased, in, 9, -, 'month-old', 'APPswe/PS1dE9', mice, but, not, in, 'APPswe/PS1dE9/jnk1+/-', animals])]). relacion([sujeto(['Furthermore,', 'JNK1', deficiency, did, not]), verbo([have]), complemento([an, effect, on, 'pro-inflammatory', marker, expression, in, the, hippocampus])]). relacion([sujeto(['Heterozygous', deficiency, of, 'JNK1', results, in, the]), verbo([decrease]), complemento([of, 'BACE1', protein, 'levels,', which, is, not, accompanied, by, the, reduction, in, the, total, number, of, 'β-amyloid', plaques, in, the, hippocampi, of, 'APPswe/PS1dE9', mice])]). relacion([sujeto(['Nevertheless,', our, results]), verbo([suggest]), complemento([that, partial, inhibition, of, 'JNK1', is, not, sufficient, to, prevent, the, neuropathological, processes, in, this, model])]). relacion([sujeto(['It', may, be, necessary, to]), verbo([inhibit]), complemento([both, the, 'JNK1', and, 'JNK3', 'simultaneously,', especially, as, previous, studies, suggest, that, 'JNK3', contributes, to, 'AD', neuropathology])]). relacion([sujeto(['Although', previous, studies]), verbo([have]), complemento([discussed, the, risk, factors, of, unplanned, suicide, behavior, in, several, 'countries,', the, unplanned, suicide, attempt, in, 'China', was, not, explored, in, a, large, sample])]). relacion([sujeto(['The', results, showed, that, the, planned, suicide, attempts, were]), verbo([associated]), complemento([with, higher, 'education,', 'hopelessness,', and, previous, suicide, act])]). relacion([sujeto(['The', reduction, in, reaching, excursion, and, hand, opening, is, thought, to, be, primarily, limited, by, abnormal, muscle, 'co-activation', of, shoulder, abductors, with, distal, limb, 'flexors,', known, as, flexion, 'synergy,', that, results, in, a]), verbo([loss]), complemento([of, independent, joint, control, or, joint, individuation])]). relacion([sujeto(['Distal', upper, extremity, joint, performance, is, directly, and, monotonically]), verbo([modulated]), complemento([by, proximal, '(', shoulder, 'abduction)', joint, demands])]). relacion([sujeto(['From', the, series, of, methods, and, the, concluding, 'recommendations,', scientists, and, clinicians, can, determine, the, ideal, robotic, quantification, method, for, the, measurement, of, the, impact, of]), verbo([loss]), complemento([of, independent, joint, control, on, reaching, and, hand, function])]). relacion([sujeto(['The', large, chorus, spatial, extent, and, its, apparent, correlation, with, regions, of, high, productivity]), verbo([suggest]), complemento([it, may, act, as, an, acoustic, beacon, to, marine, fauna, indicating, regions, of, high, biomass])]). relacion([sujeto(['These', molecules, are]), verbo([involved]), complemento([in, interactions, with, the, surrounding, environment, 'and,', in, 'pathogens,', play, critical, roles, in, the, interplay, with, the, host, immune, system])]). relacion([sujeto(['Despite', the, remarkable, diversity, in, glycoconjugate, 'structures,', most, are, assembled, by, glycosyltransferases, that]), verbo([act]), complemento([on, lipid, acceptors, at, the, cytosolic, membrane])]). relacion([sujeto(['Sulfur', dioxide, '(', 'SO2)', is, one, of, the, main, atmospheric, pollutants, 'worldwide,', and, is]), verbo([reported]), complemento([to, be, responsible, for, the, formation, of, severe, haze, in, 'China'])]). relacion([sujeto(['Some', studies]), verbo([have]), complemento([demonstrated, a, potential, harmful, effect, of, 'SO2', on, the, male, reproductive, 'system;', however, the, underlying, mechanism, is, still, unknown])]). relacion([sujeto(['After', 2, 'weeks,', the, results, showed, a, significant]), verbo([decrease]), complemento([in, body, weight, and, sperm, 'motility,', and, an, increase, in, the, testis, 'weight-to-body', weight, ratio, as, compared, to, the, control, group])]). relacion([sujeto(['Histological', investigation]), verbo([suggested]), complemento([that, 'SO2', exposure, led, to, loose, arrangement, of, the, spermatogenic, cells, and, local, structural, damage, in, the, seminiferous, tubules])]). relacion([sujeto(['Moreover,', the, expressions, of, 'P450,', 'CREM', and, 'ACT', proteins]), verbo([increased]), complemento([in, the, testes, by, 0.22, '%', ',', 47.26, '%', and, 23.38, '%', ',', respectively])]). relacion([sujeto(['Taken', 'together,', 'SO2', inhalation, lowered, sperm, 'quality,', altered, testicular, 'histology,', and]), verbo([increased]), complemento([expressions, of, 'CREM', and, 'ACT', proteins, in, the, testes, of, rats])]). relacion([sujeto(['While', much, work]), verbo([has]), complemento([been, done, to, develop, synthetic, nanocarriers, to, deliver, drugs, or, contrast, 'media,', natural, nanoparticles, such, as, lipoproteins, represent, appealing, alternatives])]). relacion([sujeto(['Lipoproteins', are, 'biocompatible,', 'biodegradable,', 'non-immunogenic', and, are, naturally]), verbo([targeted]), complemento([to, some, disease, sites])]). relacion([sujeto(['Lipoproteins', can, be, modified, to]), verbo([act]), complemento([as, contrast, agents, in, many, 'ways,', such, as, by, insertion, of, gold, cores, to, provide, contrast, for, computed, tomography])]). relacion([sujeto(['They', can, be, loaded, with, 'drugs,', nucleic, 'acids,', photosensitizers, or, boron, to]), verbo([act]), complemento([as, therapeutics])]). relacion([sujeto(['In', this, review, we, will]), verbo([provide]), complemento([background, on, 'lipoproteins,', then, survey, their, roles, as, contrast, 'agents,', in, drug, and, nucleic, acid, 'delivery,', as, well, as, in, photodynamic, therapy, and, boron, neutron, capture, therapy])]). relacion([sujeto(['The', main, goal, of, drug, delivery, systems, is, to]), verbo([target]), complemento([therapeutic, cargoes, to, desired, cells, and, to, ensure, their, efficient, uptake])]). relacion([sujeto(['Recently', a, number, of, studies]), verbo([have]), complemento([focused, on, designing, 'bio-inspired', 'nanocarriers,', such, as, 'bacteriophages,', and, synthetic, carriers, based, on, the, bacteriophage, structure])]). relacion([sujeto(['Bacteriophages', are, viruses, that, specifically]), verbo([recognize]), complemento([their, bacterial, hosts])]). relacion([sujeto(['They', can, replicate, only, inside, their, host, cell, and, can]), verbo([act]), complemento([as, natural, gene, carriers])]). relacion([sujeto(['Each', type, of, phage]), verbo([has]), complemento([a, particular, 'shape,', a, different, capacity, for, loading, 'cargo,', a, specific, production, 'time,', and, their, own, mechanisms, of, supramolecular, 'assembly,', that, have, enabled, them, to, act, as, tunable, carriers])]). relacion([sujeto(['New', 'phage-based', technologies]), verbo([have]), complemento([led, to, the, construction, of, different, peptide, 'libraries,', and, recognition, abilities, provided, by, novel, targeting, ligands])]). relacion([sujeto(['In', this, review, we, try, to, cover, the, major, phage, species, that]), verbo([have]), complemento([been, used, in, drug, and, gene, delivery, 'systems,', and, the, biological, application, of, phages, as, novel, targeting, ligands, and, targeted, therapeutics])]). relacion([sujeto(['Antiangiogenesis', therapy]), verbo([has]), complemento([been, served, as, a, potent, cancer, treatment, strategy, for, 'decades,', yet, disrupting, neovasculature, would, provoke, tumor, cells, into, invasive, growth, and, result, in, distal, metastasis])]). relacion([sujeto(['The', basic]), verbo([cause]), complemento([of, cancer, metastasis, can, be, traced, down, to, the, presence, of, circulating, tumor, cells, '(', 'CTCs)', which, detach, from, primary, tumor, site, and, act, as, '\'', 'seeds\''])]). relacion([sujeto(['Using', 'cone-and-plate', viscometer, to, create, venous, flow, 'velocity,', dTNP, was, also]), verbo([found]), complemento([to, be, able, to, capture, 'CTCs', under, shear, stress])]). relacion([sujeto(['Taken', 'together,', the, findings, here]), verbo([provided]), complemento([direct, evidence, that, the, tumor, neovasculature, and, 'CTCs', 'dual-targeting', drug, delivery, system, could, provide, a, novel, modality, for, the, treatment, of, 'highly-invasive', breast, cancer])]). relacion([sujeto(['Gibberellins', '(', 'GAs)', are, plant, hormones, that]), verbo([regulate]), complemento([most, plant, life, cycle, 'aspects,', including, flowering, and, fruit, development])]). relacion([sujeto(['DELLA', 'proteins,', negative, 'GA', response, 'regulators,']), verbo([act]), complemento([as, positive, factors, for, ovule, integument, development, in, a, mechanism, that, involves, transcription, factor, 'ABERRANT', 'TESTA', 'SHAPE', '(', 'ATS)'])]). relacion([sujeto(['In', 'fact,', 'ats-1']), verbo([has]), complemento([elevated, 'GA', levels, due, to, the, activation, of, 'GA', biosynthesis, 'genes,', which, indicates, that, 'ATS', inhibits, 'GA', biosynthesis])]). relacion([sujeto(['Moreover,', 'DELLAs', and, 'ATS', proteins, 'interact,', which]), verbo([suggests]), complemento([the, formation, of, a, transcriptional, complex, that, regulates, the, expression, of, genes, involved, in, integument, growth])]). relacion([sujeto(['Therefore,', the, repression, of, 'GA', biosynthesis, by, 'ATS', would, result, in, the, stabilization, of, 'DELLAs', to]), verbo([ensure]), complemento([correct, 'ATS-DELLA', complex, formation])]). relacion([sujeto(['The', requirement, of, both, activities, to, coordinate, proper, ovule, development, strongly, argues, that, the, 'ATS-DELLA', complex]), verbo([acts]), complemento([as, a, key, molecular, factor])]). relacion([sujeto(['This', work]), verbo([provides]), complemento([the, first, evidence, for, a, role, of, 'GAs', in, ovule, and, seed, development])]). relacion([sujeto(['Administration', of, home, parenteral, support, '(', 'HPS)']), verbo([has]), complemento([proven, to, be, 'cost-effective', over, hospital, care])]). relacion([sujeto(['In', 2010, ',', we, successfully, treated, 170, episodes, '(', 84.5, '%', ')', at, 'home,', with, 9, episodes, '(', 4.5, '%', ')']), verbo([requiring]), complemento(['ED', visits, and, 22, hospital, readmissions, '(', 11, '%', ')'])]). relacion([sujeto(['Our', protocol, helped, educate, and]), verbo([provide]), complemento([the, resources, required, to, resolve, dehydration, at, home, when, early, signs, were, recognized])]). relacion([sujeto(['The', literature]), verbo([has]), complemento([demonstrated, that, 'low-frequency/low-energy', electromagnetic, fields, do, not, cause, predictable, effects, on, 'DNA;', 'however,', they, can, epigenetically, act, on, gene, expression])]). relacion([sujeto(['The', aim, of, the, present, work, was, to, study, a, possible, epigenetic, effect, of, a, 'PEMF,']), verbo([mediated]), complemento([by, 'miRNAs,', on, a, human, glioblastoma, cell, line, '(', 'T98G)'])]). relacion([sujeto(['We', tested, a, 'PEMF', '(', maximum, magnetic, 'induction,', 2, 'mT;', 'frequency,', 75, 'Hz)', that]), verbo([has]), complemento([been, demonstrated, to, induce, autophagy, in, glioblastoma, cells])]). relacion([sujeto(['In', 'particular,', we, studied, the, effect, of, 'PEMF', on, the, expression, of, genes]), verbo([involved]), complemento([in, cancer, progression, and, a, promising, synergistic, effect, with, 'temozolomide,', a, frequently, used, drug, to, treat, glioblastoma, multiforme])]). relacion([sujeto(['We']), verbo([found]), complemento([that, electromagnetic, stimulation, in, combination, with, temozolomide, can, elicit, an, epigenetic, 'pro-apoptotic', effect, in, the, 'chemo-', and, radioresistant, 'T98G', glioblastoma, cell, line])]). relacion([sujeto(['Regulated', mRNA, translation, plays, an, important, role, in, normal, cellular, functions, and, cytoplasmic, polyadenylation, element]), verbo([binding]), complemento([proteins, '(', 'CPEBs)', are, the, key, factors, that, control, the, elongation, of, 'poly(A)', tail, during, translation])]). relacion([sujeto(['The', expression, of, various, 'CPEBs']), verbo([has]), complemento([been, noted, to, be, linked, to, 'tumorigenesis,', tumor, 'growth,', invasiveness, and, 'angiogenesis;', 'however,', different, 'CPEBs', appear, to, play, diverse, roles, in, cancer])]). relacion([sujeto(['The', evidence, from, the, literature]), verbo([suggests]), complemento([that, 'CPEB1', and, 'CPEB3', act, more, likely, as, tumor, 'suppressors;', in, 'contrast,', 'CPEB2', and, 'CPEB4', mainly, exert, oncogenic, effects])]). relacion([sujeto(['In', 'addition,', different, 'CPEB', subtypes, may]), verbo([interact]), complemento([with, each, other, to, regulate, tumorigenesis])]). relacion([sujeto(['All', four, 'CPEB', mRNAs, contain, multiple, microRNA, '(', 'miRNA)']), verbo([binding]), complemento(['sites,', while, the, functions, of, 'CPEBs', are, regulated, by, various, miRNAs])]). relacion([sujeto(['These', results, indicate, that, 'CPEBs', play, a, significant, role, in, 'tumorigenesis;', 'therefore,', manipulation, of, the, expression, of, different, subtypes, of, 'CPEBs', might]), verbo([modulate]), complemento([the, behavior, of, cancer, cells, and, provide, new, therapeutic, concepts, for, cancer, therapy])]). relacion([sujeto(['However,', more, studies, are]), verbo([required]), complemento([to, clarify, their, definite, role, in, tumor, development])]). relacion([sujeto(['The', paraventricular, nucleus, of, the, thalamus, '(', 'PVT)']), verbo([has]), complemento([been, implicated, in, behavioral, responses, to, 'reward-associated', cues])]). relacion([sujeto(['However,', the, precise, role, of, the, 'PVT', in, these, behaviors]), verbo([has]), complemento([been, difficult, to, ascertain, since, 'Pavlovian-conditioned', cues, can, act, as, both, predictive, and, incentive, stimuli])]). relacion([sujeto(['The', &, 'quot;sign-tracker/goal-tracker"', rat, model]), verbo([has]), complemento([allowed, us, to, further, elucidate, the, role, of, the, 'PVT', in, 'cue-motivated', 'behaviors,', identifying, this, structure, as, a, critical, component, of, the, neural, circuitry, underlying, individual, variation, in, the, propensity, to, attribute, incentive, salience, to, reward, cues])]). relacion([sujeto(['Thus,', presentation, of, an, incentive, stimulus, results, in, engagement, of, subcortical, brain, 'regions;', supporting, a, role, for, the, 'hypothalamic-thalamic-striatal', 'axis,', as, well, as, the, 'MeA,', in]), verbo([mediating]), complemento([responses, to, incentive, 'stimuli;', whereas, activity, in, the, 'PrL', to, 'PVT', pathway, appears, to, play, a, role, in, processing, the, predictive, qualities, of, 'reward-paired', stimuli])]). relacion([sujeto(['Lithium', can]), verbo([act]), complemento([as, an, inhibitor, of, the, kinase, 'GSK3α/β,', which, in, turn, negatively, regulates, 'β-catenin,', a, 'co-activator', of, 'LEF1/TCF', transcription, factors])]). relacion([sujeto(['However,', unclear, is, whether, therapeutic, levels, of, lithium]), verbo([activate]), complemento(['β-catenin', in, the, 'brain,', and, whether, this, activation, could, have, a, therapeutic, significance])]). relacion([sujeto(['Although', the, level, of, 'non-phospho-β-catenin']), verbo([increased]), complemento([in, all, of, the, brain, areas, 'examined,', 'β-catenin', translocated, into, cellular, nuclei, only, in, the, thalamus])]). relacion([sujeto(['We', tested, if, 'TCF7L2,', a, member, of, 'LEF1/TCF', family, that, is, highly]), verbo([expressed]), complemento([in, the, 'thalamus,', facilitated, the, activation, of, 'β-catenin'])]). relacion([sujeto(['Silencing', of, 'Tcf7l2', in, thalamic, neurons]), verbo([prevented]), complemento(['β-catenin', from, entering, the, 'nucleus,', even, when, the, cells, were, treated, with, lithium])]). relacion([sujeto(['Conversely,', when, 'Tcf7l2', was, ectopically]), verbo([expressed]), complemento([in, cortical, 'neurons,', 'β-catenin', shifted, to, the, 'nucleus,', and, lithium, augmented, this, process])]). relacion([sujeto(['Lastly,', we, silenced, tcf7l2, in, zebrafish, and, exposed, them, to, lithium, for, 3, 'days,', to, evaluate, whether, 'TCF7L2', is]), verbo([involved]), complemento([in, the, behavioral, response])]). relacion([sujeto(['Lithium']), verbo([decreased]), complemento([the, 'dark-induced', activity, of, control, 'zebrafish,', whereas, the, activity, of, zebrafish, with, tcf7l2, knockdown, was, unaltered])]). relacion([sujeto(['We', conclude, that, therapeutic, levels, of, lithium]), verbo([activate]), complemento(['β-catenin', selectively, in, thalamic, neurons])]). relacion([sujeto(['In', this, paper, we, present, a, comprehensive, study, for, the, ability, of, thermoresponsive, nanogels, '(', 'tNG)', to]), verbo([act]), complemento([as, cutaneous, penetration, enhancers])]). relacion([sujeto(['The', morphology, of, the, treated, skin, samples, was, thoroughly, investigated, by, transmission, electron, microscopy, and]), verbo([stimulated]), complemento(['Raman', spectromicroscopy])]). relacion([sujeto(['We']), verbo([found]), complemento([that, tNG, can, perturbate, the, organization, of, both, proteins, and, lipids, in, the, skin, 'barrier,', which, was, attributed, to, tNG, hydration, effects])]). relacion([sujeto(['Interestingly,', different, drug, delivery, properties, were, detected, and, the, ability, of, each, investigated, tNG, to]), verbo([enhance]), complemento([skin, penetration, correlated, well, with, the, degree, of, induced, stratum, corneum, hydration])]). relacion([sujeto(['Our', previous, study, showed, that, 'IPPA08,', a, 'cis-configuration', neonicotinoid, compound, with, unique, oxabridged, 'substructure,']), verbo([acted]), complemento([as, a, specific, synergist, to, neonicotinoid, insecticides, targeting, nicotinic, acetylcholine, receptors, '(', 'nAChRs)'])]). relacion([sujeto(['Heteropentamer', nAChRs]), verbo([have]), complemento([diverse, characteristics, and, can, form, canonical, and, noncanonical, subunit, interfaces])]). relacion([sujeto(['While', canonical, interfaces]), verbo([have]), complemento([been, exploited, as, targets, of, many, 'drugs,', noncanonical, interfaces, have, received, less, attention])]). relacion([sujeto(['In', this, 'study,', the, mechanism, of, 'IPPA08', synergism, was, evaluated, on, hybrid, nAChRs, consisting, of, three, α1, subunits, from, the, brown, planthopper, and, two, rat, β1, subunits, '(', 'Nlα1/rβ2)']), verbo([expressed]), complemento([in, 'Xenopus', oocytes])]). relacion([sujeto(['However,', at, concentrations, below, 200, &, 'nbsp;μM,', 'IPPA08', slowed, the, decay, of, inward, currents, evoked, by, 'imidacloprid,', but, not, by, 'acetylcholine,', and, also]), verbo([increased]), complemento([the, sensitivity, of, 'Nlα1/rβ2', to, imidacloprid])]). relacion([sujeto(['Experimentally']), verbo([induced]), complemento([mutations, in, canonical, '(', 'α+/β-)', and, noncanonical, '(', 'β+/α-)', interfaces, of, 'Nlα1/rβ2', receptors, were, also, examined, to, evaluate, the, presence, of, possible, binding, sites, for, 'IPPA08', on, the, receptors])]). relacion([sujeto(['Based', on, these, 'results,', we, propose, that, at, low, concentrations, 'IPPA08', can]), verbo([act]), complemento([as, a, positive, allosteric, modulator, of, noncanonical, 'interfaces,', and, likely, slow, the, decay, of, currents, through, stabilizing, the, 'open-channel', state, caused, by, the, action, of, imidacloprid, on, canonical, interfaces])]). relacion([sujeto(['Antibiotics']), verbo([inhibiting]), complemento([protein, translation, have, long, been, used, to, treat, and, prevent, infections, by, apicomplexan, parasites])]). relacion([sujeto(['These', compounds, kill, parasites, by]), verbo([inhibiting]), complemento([organellar, 'translation,', and, most, act, specifically, against, the, 'apicoplast,', a, relict, plastid, in, apicomplexans])]). relacion([sujeto(['Some', apicoplast, inhibitors]), verbo([have]), complemento([a, delayed, onset, of, 'action,', so, they, cannot, replace, 'fast-acting', 'drugs,', although, they, still, fulfil, important, roles, in, treating, and, preventing, infections])]). relacion([sujeto(['The', plethora, of, 'bacterial-like', actors, in, the, translation, machinery, of, parasite, mitochondria, and, plastids, presents, validated]), verbo([targets]), complemento([with, strong, potential, for, selectivity])]). relacion([sujeto(['Here', we, discuss, existing, drugs, that]), verbo([inhibit]), complemento([organellar, 'translation,', and, explore, targets, that, may, be, further, exploited, in, antiparasitic, drug, design])]). relacion([sujeto(['Although', the, available, pool, of, qualified, underrepresented, minority, and, women, medical, school, graduates]), verbo([has]), complemento([expanded, in, recent, 'decades,', their, representation, in, the, radiological, professions, has, improved, only, marginally])]). relacion([sujeto(['Recognizing', this, deficit, in, 'diversity,', many, professional, medical, 'societies,', including, the, 'ACR,']), verbo([have]), complemento([incorporated, these, values, as, core, elements, of, their, missions, and, instituted, programs, that, address, previously, identified, barriers, to, a, more, diverse, workforce])]). relacion([sujeto(['Radiology', leaders, are, positioned, to]), verbo([lead]), complemento([the, profession, in, expanding, the, diversity, and, improving, the, inclusiveness, of, our, professional, workforce, in, service, to, an, increasingly, diverse, society, and, patient, population])]). relacion([sujeto(['Scientists', and, 'policy-makers', globally, are, calling, for, alternative, approaches, to, conventional, intensification, of, agriculture, that]), verbo([enhance]), complemento([ecosystem, services, provided, by, biodiversity])]). relacion([sujeto(['The', evidence, reviewed, here]), verbo([suggests]), complemento([that, alternative, approaches, can, achieve, high, crop, yields, and, 'profits,', but, the, performance, of, other, socioeconomic, indicators, '(', as, well, as, 'long-term', 'trends)', is, surprisingly, poorly, documented])]). relacion([sujeto(['Given', the, impacts, of, conventional, intensification, on, biodiversity]), verbo([loss]), complemento([and, greenhouse, gas, 'emissions,', such, evidence, is, urgently, needed, to, direct, 'science-policy', 'initiatives,', such, as, the, 'United', 'Nations', '(', 'UN)', 2030, 'Agenda', for, 'Sustainable', 'Development'])]). relacion([sujeto(['Anesthesiologists', must, master, specific, legal, knowledge, to]), verbo([provide]), complemento([care, to, these, patients])]). relacion([sujeto(['Understanding', how, the, 'Law', and, the, 'Federal', 'Council', of, 'Medicine', treat, this, issue, is, critical, to, know, how, to]), verbo([act]), complemento([in, this, context])]). relacion([sujeto(['The', article, analyzes, the, 'Constitution,', 'Criminal', 'Code,', resolutions, of, the, 'Federal', 'Council', of, 'Medicine,', 'opinions,', and, jurisprudence, to, understand, the, limits, of, the, conflict, between, the, autonomy, of, will, of, 'Jehovah\'s', 'Witnesses', to, refuse, transfusion, and, the, 'physician\'s', duty, to]), verbo([provide]), complemento([the, transfusion])]). relacion([sujeto(['Humans']), verbo([have]), complemento([coevolved, over, time, to, not, only, tolerate, but, also, rely, on, trillions, of, microbes, that, aid, in, the, development, of, our, immune, 'system,', provide, 'nutrients,', break, down, potentially, noxious, 'substances,', and, act, as, a, barrier, against, potentially, pathogenic, organisms])]). relacion([sujeto(['TRIM62', '(', tripartite, motif, containing, 62, ')']), verbo([has]), complemento([been, found, to, act, as, a, tumor, suppressor, of, several, cancers])]). relacion([sujeto(['Low', expression, of, 'TRIM62', in, 'CC', tissues, was]), verbo([associated]), complemento([with, aggressive, clinicopathological, features, of, 'CC', patients])]). relacion([sujeto(['Moreover,', enforced, expression, of, 'TRIM62', in, 'CC', cells, significantly]), verbo([inhibited]), complemento([their, abilities, of, 'proliferation,', migration, and, invasion, in, vitro])]). relacion([sujeto(['Furthermore,', mechanism, study, exhibited, that, 'TRIM62', could]), verbo([suppress]), complemento(['epithelial-mesenchymal', transition, '(', 'EMT)', by, inhibiting, 'c-Jun/Slug', signaling])]). relacion([sujeto(['The', inhibitory, role, of, 'TRIM62', in, tumor, proliferation, might, be, through]), verbo([regulating]), complemento([cell, cycle, related, proteins, 'CyclinD1', and, 'P27', by, targeting, 'c-Jun'])]). relacion([sujeto(['TRIM62', is, a, potential, prognostic, biomarker, in, 'CC', and]), verbo([suppresses]), complemento([metastasis, of, 'CC', via, inhibiting, 'c-Jun/Slug', 'signaling-mediated', 'EMT'])]). relacion([sujeto(['Computational', 'methods,', such, as, topic, 'modelling,', can]), verbo([provide]), complemento([a, 'large-scale', quantitative, objective, description, of, this, content])]). relacion([sujeto(['Such', methods, may]), verbo([provide]), complemento([a, new, perspective, on, the, nature, of, engagement, on, 'ISGs', including, the, role, of, super, users, and, their, possible, effect, on, other, users])]). relacion([sujeto(['However,', super, users, were, significantly, more, likely, to, write, content, on, 5, out, of, these, 7, topics, when]), verbo([responding]), complemento([to, other, users, than, when, responding, to, fellow, super, users])]). relacion([sujeto(['The', findings]), verbo([suggest]), complemento([that, super, users, serve, the, role, of, emotionally, supportive, companions, with, a, focus, on, topics, broadly, resembling, the, 'consumer/carer', model, of, recovery])]). relacion([sujeto(['The', repertoire, of, 'free-living', protozoa, in, contact, lens, solutions, is, poorly, known, despite, the, fact, that, such, protozoa, may]), verbo([act]), complemento([as, direct, pathogens, and, may, harbor, 'intra-cellular', pathogens])]). relacion([sujeto([are]), verbo([reported]), complemento([for, the, first, time, as, contaminating, contact, lens, solutions])]). relacion([sujeto(['The', extent, to, which, sex, reversal, is]), verbo([associated]), complemento([with, transitions, in, sex, determining, systems, '(', 'XX-XY,', 'ZZ-ZW,', etc])]). relacion([sujeto(['This', is, in, large, part, because, most, amphibian, taxa]), verbo([have]), complemento([homomorphic, sex, 'chromosomes,', which, has, traditionally, made, it, challenging, to, identify, discordance, between, phenotypic, and, genetic, sex, in, 'amphibians,', despite, all, amphibians, having, a, genetic, component, to, sex, determination])]). relacion([sujeto(['The', 'DArTseq', methodology, identified, 13, 'sex-linked', 'SNP', loci, and, eight, 'presence-absence', loci]), verbo([associated]), complemento([with, 'males,', indicating, an, 'XX-XY', system])]). relacion([sujeto(['Two', other, loci]), verbo([have]), complemento([sequence, similarities, to, regions, of, the, chimpanzee, and, human, 'X-chromosome', as, well, as, the, chicken, 'Z-chromosome'])]). relacion([sujeto(['While', all, loci, are, statistically, 'sex-linked,', they, show, varying, degrees, of, female, heterozygosity, and, male, 'homozygosity,']), verbo([providing]), complemento([further, evidence, that, some, markers, are, on, regions, of, the, sex, chromosomes, undergoing, higher, rates, of, recombination, and, therefore, further, apart, from, the, putative, sex, determining, locus])]). relacion([sujeto(['The', ease, of, the, 'DArTseq', platform]), verbo([provides]), complemento([a, useful, avenue, for, future, research, on, sex, reversal, and, sex, chromosome, evolution, in, 'vertebrates,', particularly, for, 'non-model', species, with, homomorphic, or, cryptic, or, nascent, sex, chromosomes])]). relacion([sujeto(['Lin28A', and, 'Lin28B', are, highly]), verbo([conserved]), complemento(['RNA', binding, proteins, with, similar, structure, and, functions])]). relacion([sujeto(['Recent', studies, demonstrated, that, both, of, them]), verbo([act]), complemento([as, oncogenes, and, promote, cancer, progression])]). relacion([sujeto(['In', this, 'study,', we]), verbo([have]), complemento([systematically, evaluated, the, expressional, 'pattern,', mutation, status, and, correlation, of, both, 'Lin28A', and, 'Lin28B', in, colon, cancer, tissues, for, the, first, 'time,', and, compared, the, roles, of, 'Lin28A', and, 'Lin28B', in, the, 'proliferation,', 'migration,', invasion, and, apoptosis, of, colon, cancer, cells, in, vitro])]). relacion([sujeto(['We']), verbo([have]), complemento([showed, that, they, are, 'co-expressed', and, have, functional, 'similarities,', 'however,', the, molecular, mechanisms, underlying, their, similar, functions, may, not, be, identical])]). relacion([sujeto(['Flavonols', with, varied, hydroxyl, substitution, can]), verbo([act]), complemento([as, strong, antioxidants])]). relacion([sujeto(['Thanks', to, their, ability, to, chelate, metals, as, well, as, to, donate, hydrogen, atoms, they]), verbo([have]), complemento([capacity, to, scavenge, free, radicals])]). relacion([sujeto(['Most', natural, 'assets,', including, native, biodiversity, '(', our, 'focus),', are, under]), verbo([increasing]), complemento([threat, from, direct, '(', loss, of, 'habitat,', 'hunting)', and, indirect, '(', climate, 'change)', human, actions])]). relacion([sujeto(['Most', human, impacts, arise, from]), verbo([increasing]), complemento([human, populations, coupled, with, rises, in, per, capita, resource, use])]). relacion([sujeto(['The', rates, of, change, of, human, actions, generally, outpace, those, to, which, the, biota, can]), verbo([respond]), complemento([or, adapt])]). relacion([sujeto(['If', we, are, to]), verbo([maintain]), complemento([native, 'biodiversity,', then, we, must, develop, ways, to, envisage, how, the, biota, may, be, affected, over, the, next, several, decades, to, guide, management, and, policy, responses])]). relacion([sujeto(['First,', the, human, population, in, 'Australia', will, be, 40, million, by, 2050, ',', which]), verbo([has]), complemento([been, mooted, by, federal, government, agencies])]). relacion([sujeto(['There', were, few, photographs, where]), verbo([he]), complemento([and, 'Barnard', appeared, 'together,', but, because, of, the, nature, of, society, was, 'Barnard', who, won, the, 'world\'s', attention])]). relacion([sujeto(['Reactive', oxygen, species]), verbo([act]), complemento([as, important, second, messengers, in, cell, signaling, and, homeostasis, through, the, oxidation, of, protein, thiols])]). relacion([sujeto(['However,', the, dynamic, nature, of, protein, oxidation, and, the, lack, of, sensitivity, of, existing, molecular, probes]), verbo([have]), complemento([hindered, our, understanding, of, such, 'reactions;', 'therefore,', new, tools, are, required, to, address, these, challenges])]). relacion([sujeto(['In', validation, 'studies,', 'BCN-E-BCN']), verbo([binds]), complemento([the, sulfenylated, form, of, the, 'actin-severing', protein, 'cofilin,', while, mutation, of, the, cognate, cysteine, residues, abrogates, its, binding])]). relacion([sujeto(['Remarkably,', cycloaddition, of, an, 'azide-tagged', fluorophore, to, 'BCN-E-BCN', labelled, proteins, produced, in, vivo, can, be, visualized, by, fluorescence, microscopy, to]), verbo([reveal]), complemento([their, subcellular, localization])]). relacion([sujeto(['Many', patients, undergoing, orthodontic, treatment, desire, to]), verbo([have]), complemento([a, straight, and, well, aligned, 'dentition,', but, also, whiter, teeth])]). relacion([sujeto(['However,', a, deeper, understanding, of, the, bleaching, process]), verbo([suggests]), complemento([that, the, oxidation, caused, by, 'products,', which, results, from, hydrogen, peroxide, 'decomposition,', are, able, to, diffuse, peripherally, into, the, tooth, structure, and, reach, even, that, under, the, cemented, brackets])]). relacion([sujeto(['All', biological, criteria]), verbo([have]), complemento([been, fulfilled, satisfying, 'patients\'', expectations, of, aligned, and, whitened, teeth, in, less, time, than, if, treatments, had, been, performed, 'separately,', with, satisfactory, results, and, no, esthetic, loss])]). relacion([sujeto(['The', 'in-office', bleaching, treatment, with, brackets, in, position, also, may]), verbo([act]), complemento([as, a, motivation, 'factor,', preventing, patient, withdrawal, or, treatment, interruption])]). relacion([sujeto(['Through', the, most, recent, 'surveys,', this, analysis, is, aimed, to, several, processes, by, which, the, various, epigenetic, types, who, are, different, from, one, to, another, subject, may]), verbo([act]), complemento([on, the, methabolism, 'key-genes,', like, that, they, even, indirectly, arouse, the, straight, onset, of, one, or, more, methabolic, 'syndromes:', the, risk, of, passing, this, syndrome, to, next, offsprings, is, more, or, less, high])]). relacion([sujeto(['Through', the, new, later, surveyes, who, are, originated, from, analysis, undertaken, on, animals, and, experiments, on, men, by, in, vitro, and, in, vivo, test, on]), verbo([has]), complemento([proved, how, much, the, epigenetic, modifications, are, affected, either, by, the, environmental, 'compounds,', often, going, back, to, maternal, and, prenatal, 'nourishment,', or, by, the, more, or, less, strong, connection, to, the, transcriptional, genetic, control, :, this, occurs, to, the, stochastic, eventuality, to, pass, the, methabolic, syndrome, 'phenotype\'s', to, the, following, cohorts])]). relacion([sujeto(['Mainly', in, an, individual, observation, these, risks, evaluation, is, until, now, 'indefined,', buti, t, is, going, in, progress, and, one]), verbo([has]), complemento([still, waiting, the, issues, of, next, new, performed, surveyes, to, can, enlight, on, some, interconnection, that, is, following, the, histonic, methilation, and, the, 'micro-RNA', not, codifyng, control, role, on, some, gene, who, is, involved, in, these, methabolic, 'syndromes;', this, process, is, variable, from, one, to, another, subject])]). relacion([sujeto(['Accurately', assessing, the, physiological, status, of, firefighters, during, work, in, the, heat, is, critical, to]), verbo([ensuring]), complemento([their, safety])]). relacion([sujeto(['Polydeoxyribonucleotides', '(', 'PDRNs)', are, low, molecular, weight, 'DNA', molecules, of, natural, origin, that]), verbo([stimulate]), complemento([cell, migration, and, 'growth,', extracellular, matrix, '(', 'ECM)', protein, production, and, reduce, inflammation])]). relacion([sujeto(['A', total, of, 29, studies, were]), verbo([found]), complemento([by, 'PubMed', and, www])]). relacion([sujeto(['PDRNs', are, usually, administered, from, a, minimum, of, 3, to, a, maximum, of, 5, times, and, they]), verbo([act]), complemento([trough, the, activation, of, 'A2A', receptor])]). relacion([sujeto(['Four', histidine, residues, '(', 'His37)', in, the, center, of, the, channel]), verbo([act]), complemento([as, a, pH, sensor, and, proton, selectivity, filter])]). relacion([sujeto(['Despite', intense, 'study,', the, 'pH-dependent', activation, mechanism, of, the, 'AM2', channel]), verbo([has]), complemento([to, date, not, been, completely, understood, at, a, molecular, level])]). relacion([sujeto(['Herein', we]), verbo([have]), complemento([used, multiscale, computer, simulations, to, characterize, '(', with, explicit, proton, transport, free, energy, profiles, and, their, associated, calculated, 'conductances)', the, activation, mechanism, of, 'AM2'])]). relacion([sujeto(['All', proton, transfer, steps]), verbo([involved]), complemento([in, proton, diffusion, through, the, 'channel,', including, the, 'protonation/deprotonation', of, 'His37,', are, explicitly, considered, using, 'classical,', 'quantum,', and, reactive, molecular, dynamics, methods])]). relacion([sujeto(['Plants', use, intracellular, immunity, 'receptors,', known, as, 'nucleotide-binding', oligomerization, 'domain-like', receptors, '(', 'NLRs),', to]), verbo([recognize]), complemento([specific, pathogen, effector, proteins, and, induce, immune, responses])]). relacion([sujeto(['These', proteins]), verbo([provide]), complemento([resistance, to, many, of, the, 'world\'s', most, destructive, plant, 'pathogens,', yet, we, have, a, limited, understanding, of, the, molecular, mechanisms, that, lead, to, defense, signaling])]). relacion([sujeto(['We', demonstrate, that, these, regions, 'are,', in, 'fact,', largely, monomeric, and, adopt, similar, folds, in, solution, in, all, three, 'proteins,']), verbo([suggesting]), complemento([that, the, 'CC', domains, from, plant, 'NLRs', adopt, a, conserved, fold])]). relacion([sujeto(['The', minimal, region, of, the, 'CC', domain]), verbo([required]), complemento([for, both, cell, death, signaling, and, 'self-association', extends, to, amino, acid, 142, ',', thus, including, 22, residues, absent, from, previous, biochemical, and, structural, protein, studies])]). relacion([sujeto(['These', data]), verbo([suggest]), complemento([that, 'self-association', of, the, minimal, 'CC', domain, is, necessary, for, signaling, but, is, likely, to, involve, a, different, structural, basis, than, previously, suggested, by, the, 'MLA10', crystallographic, dimer])]). relacion([sujeto(['Large-scale', corporate, 'projects,', particularly, those, in, extractive, industries, or, hydropower, 'development,']), verbo([have]), complemento([a, history, from, early, in, the, twentieth, century, of, creating, negative, 'environmental,', 'social,', and, health, impacts, on, communities, proximal, to, their, operations])]). relacion([sujeto(['These', projects]), verbo([triggered]), complemento([an, activist, opposition, that, progressively, expanded, and, became, influential, at, both, the, host, community, level, and, with, multilateral, financial, institutions])]). relacion([sujeto(['In', parallel, 'to,', and, spurred, 'by,', this, 'activism,', a, shift, occurred, in, 1969, with, the, passage, of, the, 'National', 'Environmental', 'Policy', 'Act', in, the, 'United', 'States,', which]), verbo([required]), complemento(['Environmental', 'Impact', 'Assessment', '(', 'EIA)', for, certain, types, of, industrial, and, infrastructure, projects])]). relacion([sujeto(['Over', the, last, four, 'decades,', there]), verbo([has]), complemento([been, a, global, movement, to, develop, a, formal, 'legal/regulatory', 'EIA', process, for, large, industrial, and, infrastructure, projects])]). relacion([sujeto(['In', 'addition,', 'social,', 'health,', and, human, rights, impact, 'assessments,', with]), verbo([associated]), complemento([mitigation, 'plans,', were, sequentially, initiated, and, have, increasingly, influenced, project, design, and, relations, among, 'companies,', host, 'governments,', and, locally, impacted, communities])]). relacion([sujeto(['Often,', beneficial, 'community-level', 'social,', 'economic,', and, health, programs]), verbo([have]), complemento([voluntarily, been, put, in, place, by, companies])]). relacion([sujeto(['Recent', studies]), verbo([have]), complemento([suggested, that, epigenetic, regulation, such, as, 'DNA', methylation, is, involved, in, 'heterosis,', but, the, molecular, mechanism, of, heterosis, is, still, unclear])]). relacion([sujeto(['To', address, the, epigenetic, contribution, to, heterosis, in, 'Arabidopsis', 'thaliana,', we, used, mutant, genes, that]), verbo([have]), complemento([roles, in, 'DNA', methylation])]). relacion([sujeto(['Hybrids', with, a, mutation, in]), verbo([decrease]), complemento([in, dna, methylation, 1, '(', 'ddm1)', showed, a, decreased, heterosis, level])]). relacion([sujeto(['Vegetative', heterosis, in, the, ddm1, mutant, hybrid, was, reduced, but, not, 'eliminated;', a, complete, reduction, could, result, if, there, was, a, change, in, methylation, at, all, loci, critical, for, generating, the, level, of, 'heterosis,', whereas, if, only, a, proportion, of, the, loci]), verbo([have]), complemento([methylation, changes, there, may, only, be, a, partial, reduction, in, heterosis])]). relacion([sujeto(['The', flow, of, excitation, energy, and, electrons, in, the, photosynthetic, apparatus, needs, to, be, continuously]), verbo([modulated]), complemento([to, respond, to, dynamics, of, environmental, 'conditions,', and, 'Flavodiiron', '(', 'FLV)', proteins, are, seminal, components, of, this, regulatory, machinery, in, cyanobacteria])]). relacion([sujeto(['The', lack, of, 'FLVs', was, partially, compensated, for, by, an]), verbo([increased]), complemento([cyclic, electron, 'transport,', suggesting, that, in, flowering, 'plants,', the, 'FLV\'s', role, was, taken, by, other, alternative, electron, routes])]). relacion([sujeto(['Globally,', 'Arctic', and, 'Subarctic', regions]), verbo([have]), complemento([experienced, the, greatest, temperature, increases, during, the, last, 30, &, 'nbsp;years'])]). relacion([sujeto(['These', extreme, changes]), verbo([have]), complemento([amplified, threats, to, the, freshwater, ecosystems, that, dominate, the, landscape, in, many, areas, by, altering, water, budgets])]). relacion([sujeto(['Several', studies, in, temperate, environments]), verbo([have]), complemento([examined, the, adaptive, capacity, of, organisms, to, enhance, our, understanding, of, the, potential, repercussions, of, warming, and, associated, accelerated, drying, for, freshwater, ecosystems])]). relacion([sujeto(['However,', few, experiments]), verbo([have]), complemento([examined, these, impacts, in, 'Arctic', or, 'Subarctic', freshwater, 'ecosystems,', where, the, climate, is, changing, most, rapidly])]). relacion([sujeto(['We', predicted, wetland, warming, and, drying, would]), verbo([act]), complemento(['synergistically,', with, water, temperature, partially, compensating, for, some, of, the, negative, effects, of, accelerated, drying])]). relacion([sujeto(['Across', all, drying, 'regimes,', a, 1, &, 'nbsp;°C']), verbo([increase]), complemento([in, water, temperature, increased, the, odds, of, survival, by, 1.79, ',', and, tadpoles, in, 52, -, day, and, 64, -, day, hydroperiod, mesocosms, were, 4.1, -, 4.3, times, more, likely, to, survive, to, metamorphosis, than, tadpoles, in, 45, -, day, mesocosms])]). relacion([sujeto(['As', 'expected,']), verbo([increased]), complemento([temperatures, accelerated, tadpole, growth, through, day, 30, of, the, experiment])]). relacion([sujeto(['Our', results]), verbo([reveal]), complemento([that, one, of, the, dominant, herbivores, in, 'Subarctic', 'wetlands,', wood, frog, 'tadpoles,', are, capable, of, increasing, their, developmental, rates, in, response, to, increased, temperature, and, accelerated, 'drying,', but, only, in, an, additive, manner])]). relacion([sujeto(['The', strong, negative, effects, of, drying, on, 'survival,', combined, with, lack, of, compensation, between, these, two, environmental, 'drivers,']), verbo([suggest]), complemento([changes, in, the, aquatic, environment, that, are, expected, in, this, ecosystem, will, reduce, mean, fitness, of, populations, across, the, landscape])]). relacion([sujeto(['Small', 'GTPases', in, the, 'Rho', family]), verbo([act]), complemento([as, major, nodes, with, functions, beyond, cytoskeletal, rearrangements, shaping, the, 'Caenorhabditis', elegans, embryo, during, development])]). relacion([sujeto(['elegans,', the, best, studied, members, of, these, highly]), verbo([conserved]), complemento(['Rho', family, small, 'GTPases,', 'RHO-1/RhoA,', 'CED-10/Rac,', and, 'CDC-42,', are, crucial, in, several, cellular, processes, dealing, with, cytoskeletal, reorganization])]). relacion([sujeto(['Surprisingly,', 'np-Au', films, with, thicker, ligaments]), verbo([lead]), complemento([to, an, increase, in, electrical, 'resistance,', which, is, unexpected, since, the, extent, of, charge, carrier, scattering, at, the, ligament, surface, should, decrease, with, increasing, ligament, size])]). relacion([sujeto(['This']), verbo([suggests]), complemento([that, grains, act, as, scattering, centers, for, charge, carriers, and, this, becomes, the, dominant, mechanism, in, dictating, electrical, resistance, in, a, percolated, network, of, thin, conductive, ligaments])]). relacion([sujeto(['One', out, of, every, two, children, in, the, pediatric, intensive, care, unit, '(', 'PICU)', will, develop, malnutrition, or]), verbo([have]), complemento([worsening, of, baseline, malnutrition, and, present, with, specific, micronutrient, deficiencies])]). relacion([sujeto(['Early', and, adequate, enteral, nutrition, '(', 'EN)', is]), verbo([associated]), complemento([with, improved, 60, -, day, survival, after, pediatric, critical, 'illness,', 'and,', 'yet,', despite, early, 'EN', 'guidelines,', critically, ill, children, receive, on, average, only, 55, '%', of, goal, calories, by, 'PICU', day, 10])]). relacion([sujeto(['Strategies', to, improve, early, initiation, and, advancement, and, to]), verbo([maintain]), complemento([delivery, of, 'EN', are, needed, to, improve, morbidity, and, mortality, from, pediatric, 'ARDS'])]). relacion([sujeto(['The', gut, is, thought, to]), verbo([act]), complemento([as, a, &, 'quot;motor"', of, organ, 'dysfunction,', and, emerging, data, regarding, the, role, of, intestinal, barrier, functions, and, the, intestinal, microbiome, on, organ, dysfunction, and, outcomes, of, critical, illness, present, exciting, opportunities, to, improve, patient, outcomes])]). relacion([sujeto(['Precise', nutritional, 'therapies,', which, are, titrated, and]), verbo([targeted]), complemento([to, preservation, of, intestinal, barrier, 'function,', prevention, of, intestinal, 'dysbiosis,', preservation, of, lean, body, 'mass,', and, blunting, of, the, systemic, inflammatory, 'response,', offer, great, potential, for, improving, outcomes, of, pediatric, 'ARDS'])]). relacion([sujeto(['We', will, examine, emerging, data, regarding, the, role, of, the, intestinal, microbiome, in]), verbo([modulating]), complemento([the, response, to, critical, illness])]). relacion([sujeto(['Dental', caries]), verbo([has]), complemento([been, traditionally, described, as, a, multifactorial, disease, that, involves, the, interaction, of, various, factors, like, 'host,', 'agent,', substrate, and, time])]). relacion([sujeto(['Landmark', studies]), verbo([have]), complemento([established, the, fact, that, 'Mutans', 'Streptococci', are, the, primary, etiologic, agents, of, dental, caries])]). relacion([sujeto(['The', mean, pre, rinse, 'CFU', was, significantly, higher, than, post, rinse, 'CFU', for, all, the, study, 'groups,']), verbo([suggesting]), complemento([that, all, the, four, mouth, rinses, were, effective, in, decreasing, the, levels, of, 'Streptococcus', mutans, in, the, saliva])]). relacion([sujeto(['Psychiatric', diseases, like, 'anxiety,', 'depression,', schizophrenia, and, bipolar, disorders, are]), verbo([increasing]), complemento([at, an, alarming, rate])]). relacion([sujeto(['These', diseases, can, affect, the, quantity, and, quality, of, saliva]), verbo([leading]), complemento([to, multiple, oral, diseases])]). relacion([sujeto(['Although', many, researchers]), verbo([have]), complemento([evaluated, xerostomia, in, general, 'population,', its, prevalence, is, not, been, assessed, in, patients, suffering, from, different, psychological, disorders])]). relacion([sujeto(['An', equal, number, of, healthy, individuals]), verbo([reporting]), complemento([to, oral, medicine, department, for, routine, oral, screening, were, included, as, control, group, after, initial, psychiatric, evaluation])]). relacion([sujeto(['In', this, study, statistically, significant]), verbo([increase]), complemento([in, the, xerostomia, in, psychiatric, patients, was, recorded, when, compared, to, the, control, group, '(', 'p<0'])]). relacion([sujeto(['Emotional', alterations, may]), verbo([act]), complemento([as, a, precipitating, factor, that, could, influence, the, salivary, secretion, resulting, in, multiple, oral, diseases])]). relacion([sujeto(['Live', 'Donor', 'Liver', 'Transplantation', '(', 'LDLT)', is, an]), verbo([act]), complemento([of, selflessness, on, the, part, of, the, donor, who, is, subjected, to, a, major, hepatectomy])]). relacion([sujeto(['diminuta)', is, prevalent, 'worldwide,', and, a, few, hundred, human, cases]), verbo([have]), complemento([been, reported, till, date])]). relacion([sujeto(['It', is, primarily, a, rodent, parasite, and, humans, '(', usually, 'children)', can]), verbo([act]), complemento([as, accidental, hosts])]). relacion([sujeto(['Infections', are, usually, asymptomatic, but, abdominal, 'pain,', 'irritability,', 'pruritis,', mild, diarrhoea, and, eosinophilia, are, among, the, existing, symptoms, in, a, few, of, the]), verbo([reported]), complemento([cases])]). relacion([sujeto(['Here,', we]), verbo([report]), complemento([a, case, of, an, 11, -, 'year-old', female, child, from, 'Bijnor,', who, presented, to, us, with, complaints, of, abdominal, 'pain,', fatigue, and, irregular, episodes, of, fever])]). relacion([sujeto(['This', case, is, presented, to, emphasize, that, till, date, there, are, very, few]), verbo([reports]), complemento([on, 'H'])]). relacion([sujeto(['These', levels, indicate, that, in, the, absence, of, 'CRE', 'screenings,', proper, isolation, of, carrier, patients, is, not, 'possible,']), verbo([leading]), complemento([to, possible, spreading, of, these, resistant, bacteria, strains, in, 'ICUs'])]). relacion([sujeto(['A', longer, period, of, study, is]), verbo([required]), complemento([to, obtain, more, substantial, data, to, validate, the, results, of, this, pilot])]). relacion([sujeto(['There', are, 'situations,', where, there, is, no, available, accompanying, near, relatives, of, the, 'deceased,', which, pose, a, challenge, for, personnel]), verbo([involved]), complemento([in, the, process, of, body, donation])]). relacion([sujeto(['In', two, of, the]), verbo([reported]), complemento(['cases,', the, body, donation, was, done, by, the, 'live-in', partner, and, a, friend, of, the, deceased])]). relacion([sujeto(['In', another]), verbo([reported]), complemento(['case,', the, son, of, the, deceased, was, nominated, by, the, donor, at, the, time, of, registration])]). relacion([sujeto(['As', the]), verbo([son]), complemento([of, the, deceased, was, not, available, at, the, time, of, death, of, the, 'donor,', donation, was, executed, by, another, near, relative])]). relacion([sujeto(['None', of, the, 'Anatomy', 'Acts', of, various, 'States', in, 'India']), verbo([provide]), complemento([an, alternative, in, the, absence, of, near, relatives, for, claiming, the, body, or, for, donating, the, 'body,', except, for, 'Acts', of, 'Delhi', and, 'Kerala'])]). relacion([sujeto(['Philosophical', arguments, stemming, from, the, public, health, ethics, arena]), verbo([suggest]), complemento([that, public, health, interventions, ought, to, be, subject, to, normative, inquiry, that, considers, relational, 'values,', including, concepts, such, as, 'solidarity,', reciprocity, and, health, equity])]). relacion([sujeto(['These', findings, underscore, how, normative, dimensions, pertaining, to, 'men\'s', decisions, to, test, are, dialectically, interrelated, with, the, broader, social, and, structural, influences, on, individual, and, collective, 'health-related', 'behaviour,', thereby]), verbo([suggesting]), complemento([a, need, to, advance, an, explicit, 'empirical-normative', research, agenda, related, to, population, and, public, health, intervention, research])]). relacion([sujeto(['Delivered', into, plant, cells, by, type, 'III', secretion, from, pathogenic, 'Xanthomonas', 'species,', 'TAL', '(', transcription, 'activator-like)', effectors, are, 'nuclear-localized,', 'DNA-binding', proteins, that, directly]), verbo([activate]), complemento([specific, host, genes])]). relacion([sujeto(['Targets', include, genes, important, for, 'disease,', genes, that]), verbo([confer]), complemento(['resistance,', and, genes, inconsequential, to, the, 'host-pathogen', interaction])]). relacion([sujeto(['TAL', effector, specificity, is, encoded, by, polymorphic, repeats, of, 33, -, 35, amino, acids, that]), verbo([interact]), complemento(['one-to-one', with, nucleotides, in, the, recognition, site])]). relacion([sujeto(['Activity', depends, also, on, 'N-terminal', sequences, important, for, 'DNA']), verbo([binding]), complemento([and, 'C-terminal', nuclear, localization, signals, '(', 'NLS)', and, an, acidic, activation, domain, '(', 'AD)'])]). relacion([sujeto([oryzae, '(', 'Xoo),', which]), verbo([cause]), complemento([bacterial, leaf, streak, and, bacterial, blight, of, 'rice,', respectively])]). relacion([sujeto(['Here', we]), verbo([provide]), complemento([evidence, that, these, sequences, encode, proteins, we, call, &, 'quot;truncTALEs,"', for, &, 'quot;truncated', 'TAL', effectors])]). relacion([sujeto([&, 'quot;', 'We', show, that, truncTALE, 'Tal2h', of, 'Xoc', strain, 'BLS256,', and, by, correlation, truncTALEs, in, other, 'strains,', specifically]), verbo([suppress]), complemento([resistance, mediated, by, the, 'Xo1', locus, recently, described, in, the, heirloom, rice, variety, 'Carolina', 'Gold'])]). relacion([sujeto(['Xo1-mediated', resistance, is]), verbo([triggered]), complemento([by, different, 'TAL', effectors, from, diverse, 'X'])]). relacion([sujeto([oryzae, 'strains,', irrespective, of, their, 'DNA']), verbo([binding]), complemento(['specificity,', and, does, not, require, the, 'AD'])]). relacion([sujeto(['And,', in, 'vitro,', 'Tal2h', did, not]), verbo([bind]), complemento([any, of, several, potential, recognition, sites])]). relacion([sujeto(['Many', truncTALEs]), verbo([have]), complemento([one, 28, aa, 'repeat,', a, length, not, observed, previously])]). relacion([sujeto(['Tested', in, an, engineered, 'TAL', 'effector,', this, repeat]), verbo([required]), complemento([a, single, base, pair, deletion, in, the, 'DNA,', suggesting, that, it, or, a, neighbor, disengages])]). relacion([sujeto(['The', presence, of, the, 28, aa, 'repeat,', 'however,', was, not]), verbo([required]), complemento([for, resistance, suppression])]). relacion([sujeto(['We', propose, that, 'Tal2h', and, other, truncTALEs]), verbo([act]), complemento([as, dominant, negative, ligands, for, an, immune, receptor, encoded, by, the, 'Xo1', 'locus,', likely, a, nucleotide, 'binding,', 'leucine-rich', repeat, protein])]). relacion([sujeto(['Although', several, efforts]), verbo([have]), complemento([been, made, in, the, search, for, genetic, and, epigenetic, patterns, linked, to, 'diseases,', a, comprehensive, explanation, of, the, mechanisms, underlying, pathological, phenotypic, plasticity, is, still, far, from, being, clarified])]). relacion([sujeto(['Oxidative', stress, and, inflammation, are, two, of, the, major]), verbo([triggers]), complemento([of, the, epigenetic, alterations, occurring, in, chronic, 'pathologies,', such, as, neurodegenerative, diseases])]). relacion([sujeto(['In', 'fact,', over, the, last, 'decade,', remarkable, progress]), verbo([has]), complemento([been, made, to, realize, that, 'chronic,', 'low-grade', inflammation, is, one, of, the, major, risk, factor, underlying, brain, aging])]). relacion([sujeto(['Accumulated', data, strongly]), verbo([suggest]), complemento([that, phytochemicals, from, 'fruits,', 'vegetables,', 'herbs,', and, spices, may, exert, relevant, immunomodulatory, 'and/or', 'anti-inflammatory', activities, in, the, context, of, brain, aging])]). relacion([sujeto(['Starting', by, the, evidence, that, a, common, denominator, of, aging, and, chronic, degenerative, diseases, is, represented, by, 'inflammation,', and, that, several, dietary, phytochemicals, are, able, to, potentially, interfere, with, and]), verbo([regulate]), complemento([the, normal, function, of, 'cells,', in, particular, neuronal, 'components,', aim, of, this, review, is, to, summarize, recent, studies, on, neuroinflammaging, processes, and, proofs, indicating, that, specific, phytochemicals, may, act, as, positive, modulators, of, neuroinflammatory, events])]). relacion([sujeto(['In', 'addition,', critical, pathways]), verbo([involved]), complemento([in, mediating, phytochemicals, effects, on, neuroinflammaging, were, 'discussed,', exploring, the, real, impact, of, these, compounds, in, preserving, brain, health, before, the, onset, of, symptoms, leading, to, inflammatory, neurodegeneration, and, cognitive, decline])]). relacion([sujeto(['Recently', we, showed, that, growth, of, 'post-mitotic', neuroendocrine, cells]), verbo([expressing]), complemento([the, basic, helix, loop, helix, '(', 'bHLH)', transcription, factor, 'Dimmed', '(', 'Dimm)', in, 'Drosophila', could, be, regulated, by, 'insulin/IGF', signaling, and, the, insulin, receptor, '(', 'dInR)'])]). relacion([sujeto(['Dimm', is, also, known, to]), verbo([confer]), complemento([a, secretory, phenotype, to, neuroendocrine, cells, and, can, be, part, of, a, combinatorial, code, specifying, terminal, differentiation, in, peptidergic, neurons])]). relacion([sujeto(['To', further, understand, the, mechanisms, of, 'Dimm', function, we, ectopically]), verbo([expressed]), complemento(['Dimm', or, 'Dimm', together, with, dInR, in, a, wide, range, of, 'Dimm', positive, and, 'Dimm', negative, peptidergic, 'neurons,', sensory, 'neurons,', 'interneurons,', motor, 'neurons,', and, gut, endocrine, cells])]). relacion([sujeto(['We']), verbo([provide]), complemento([further, evidence, that, dInR, mediated, cell, growth, occurs, in, a, 'Dimm', dependent, manner, and, that, one, source, of, 'insulin-like', peptide, '(', 'DILP)', for, dInR, mediated, cell, growth, in, the, 'CNS', is, 'DILP6', from, glial, cells])]). relacion([sujeto(['Expressing', both, 'Dimm', and, dInR, in, 'Dimm', negative, neurons]), verbo([induced]), complemento([growth, of, cell, 'bodies,', whereas, dInR, alone, did, not])]). relacion([sujeto(['We', also]), verbo([found]), complemento([that, 'Dimm', alone, can, regulate, cell, growth, depending, on, specific, cell, type])]). relacion([sujeto(['This', may, be, explained, by, the]), verbo([finding]), complemento([that, the, dInR, is, a, direct, target, of, 'Dimm'])]). relacion([sujeto(['Conditional', gene]), verbo([targeting]), complemento([experiments, showed, that, 'Dimm', alone, could, affect, cell, growth, in, certain, neuron, types, during, metamorphosis, or, in, the, adult, stage])]). relacion([sujeto(['Another', important]), verbo([finding]), complemento([was, that, ectopic, 'Dimm', inhibits, apoptosis, of, several, types, of, neurons, normally, destined, for, programmed, cell, death, '(', 'PCD)'])]). relacion([sujeto(['Taken', together, our, results]), verbo([suggest]), complemento([that, 'Dimm', plays, multiple, transcriptional, roles, at, different, developmental, stages, in, a, cell, 'type-specific', manner])]). relacion([sujeto(['In', some, cell, types, ectopic, 'Dimm', may]), verbo([act]), complemento([together, with, resident, combinatorial, code, transcription, factors, and, affect, terminal, 'differentiation,', as, well, as, act, in, transcriptional, networks, that, participate, in, long, term, maintenance, of, neurons, which, might, lead, to, blocked, apoptosis])]). relacion([sujeto(['Understanding', how, new, 'Medicaid', enrollees, are, approaching, their, own, health, and, health, care, in, the, shifting, health, care, landscape, of, the, 'Affordable', 'Care', 'Act']), verbo([has]), complemento([implications, for, future, outreach, and, enrollment, 'efforts,', as, well, as, service, planning, for, this, population])]). relacion([sujeto(['The', chemokine, receptor, 'CXCR4', and, its, chemokine, ligand, 'CXCL12']), verbo([mediate]), complemento([directed, cell, migration, during, 'organogenesis,', immune, responses, and, also, metastatic, disease])]). relacion([sujeto(['Here,', we, show, that, the, 'β-arrestin1/STAM1', 'complex,', initially, identified, to, govern, lysosomal, trafficking, of, 'CXCR4,', also]), verbo([mediates]), complemento(['CXCR4-dependent', chemotaxis])]). relacion([sujeto(['The', 'β-arrestin1/STAM1', complex, is, necessary, for]), verbo([promoting]), complemento([autophosphorylation, of, focal, adhesion, kinase, '(', 'FAK)'])]). relacion([sujeto(['FAK', is, necessary, for, 'CXCL12-induced', chemotaxis, and]), verbo([associates]), complemento([with, and, localizes, with, 'β-arrestin1', and, 'STAM1', in, a, 'CXCL12-dependent', manner])]). relacion([sujeto(['Our', data]), verbo([reveal]), complemento([previously, unknown, roles, for, 'β-arrestin1', and, 'STAM1', in, 'CXCR4-dependent', 'chemotaxis,', which, we, propose, act, in, concert, to, regulate, 'FAK', signaling])]). relacion([sujeto(['The', 'β-arrestin1/STAM1', complex, is, a, promising]), verbo([target]), complemento([for, blocking, 'CXCR4-promoted', 'FAK', autophosphorylation, and, chemotaxis])]). relacion([sujeto(['PGC-1-related', coactivator, '(', 'PRC)']), verbo([has]), complemento([a, dual, function, in, 'growth-regulated', mitochondrial, biogenesis, and, as, a, sensor, of, metabolic, stress])]). relacion([sujeto(['PRC', induction, by, mitochondrial, 'inhibitors,', intracellular, 'ROS,', or, topoisomerase, 'I', inhibition, orchestrates, an, inflammatory, program]), verbo([associated]), complemento([with, the, adaptation, to, cellular, stress])]). relacion([sujeto(['PRC', 'steady-state', expression, was, markedly]), verbo([increased]), complemento([upon, mutation, of, two, 'GSK-3', serine, phosphorylation, sites, within, the, 'carboxyl-terminal', domain])]). relacion([sujeto(['Unlike', 'PRC,', which, was]), verbo([induced]), complemento(['post-translationally', through, increased, protein, 'half-life,', 'c-MYC', was, induced, predominantly, at, the, mRNA, level])]). relacion([sujeto(['MK-2206', also]), verbo([inhibited]), complemento([the, 'phosphor-inactivation', of, 'GSK-3β', by, 'CCCP,', a, result, consistent, with, the, ability, of, 'Akt', to, 'phosphorylate,', and, thereby, suppress, 'GSK-3', activity])]). relacion([sujeto(['Thus,', 'PRC', and, 'c-MYC', can]), verbo([act]), complemento([in, concert, through, 'Akt-GSK-3', signaling, to, reprogram, gene, expression, in, response, to, mitochondrial, stress])]). relacion([sujeto(['Recent', evidence]), verbo([suggests]), complemento([involvement, of, coagulation, factor, 'XIa', '(', 'FXIa)', in, thrombotic, event, development])]). relacion([sujeto(['In', thrombin, generation, 'assays,', for]), verbo([increasing]), complemento([concentrations, of, 'E-FXIa', with, 'low,', but, not, with, high, 'TF', 'concentrations,', peak, thrombin, significantly, increased, whereas, lag, time, and, time, to, peak, significantly, decreased])]). relacion([sujeto(['Similar', dependencies, of, lag, times, and, rates, of, thrombin, generation, were]), verbo([found]), complemento([in, mathematical, model, simulations])]). relacion([sujeto(['In', both, in, vitro, and, in, silico, experiments, that, included, 'E-FXIa,', thrombin, bursts, were, seen, for, 'TF', levels, much, lower, than, those]), verbo([required]), complemento([without, 'E-FXIa'])]). relacion([sujeto(['For', in, silico, thrombin, bursts, initiated, by, the, synergistic, action, of, 'TF', and, 'E-FXIa,', the, mechanisms]), verbo([leading]), complemento([to, the, burst, differed, substantially, from, those, for, bursts, initiated, by, high, 'TF', alone])]). relacion([sujeto(['Furthermore,', the, initiation, of, thrombin, bursts, by, high, 'TF', levels, relied, on, different, platelet, 'FIX/FIXa']), verbo([binding]), complemento([sites, than, those, involved, in, bursts, initiated, by, low, 'TF', levels, with, 'E-FXIa'])]). relacion([sujeto(['Low', concentrations, of, 'TF', and, exogenous, 'FXIa,', each, too, low, to, elicit, a, burst, in, thrombin, production, 'alone,']), verbo([act]), complemento([synergistically, when, in, combination, to, cause, substantial, thrombin, production])]). relacion([sujeto(['The', observation, about, 'FIX/FIXa']), verbo([binding]), complemento([sites, may, have, therapeutic, implications])]). relacion([sujeto(['In', 'addition,', it, was, evaluated, the, effects, of, 'AR-A0144818,', a, 'GSK-3β', 'inhibitor,', on, 'manic-like', behaviour]), verbo([induced]), complemento([by, 'OUA'])]). relacion([sujeto(['OUA']), verbo([decreased]), complemento(['pPI3K,', pAkt, and, 'pGSK-3β', levels])]). relacion([sujeto(['In', 'addition,', 'AR-A0144818', reversed, the, 'manic-like', behavior]), verbo([induced]), complemento([by, 'OUA'])]). relacion([sujeto(['These', findings]), verbo([suggest]), complemento([that, the, 'manic-like', effects, of, ouabain, are, associated, with, the, activation, of, 'GSK-3β,', and, that, 'Li', and, 'VPA', exert, protective, effects, against, 'OUA-induced', inhibition, on, 'GSK-3β', pathway])]). relacion([sujeto(['Oxidative', stress, is]), verbo([involved]), complemento([in, various, and, numerous, pathological, states, including, several, 'age-related', neurodegenerative, diseases])]). relacion([sujeto(['Peroxidation', of, the, membrane, lipid, bilayer, is, one, of, the, major, sources, of, free, 'radical-mediated', injury, that, directly, damages, neurons]), verbo([causing]), complemento([increased, membrane, 'rigidity,', decreased, activity, of, 'membrane-bound', 'enzymes,', impairment, of, membrane, receptors, and, altered, membrane, permeability, and, eventual, cell, death])]). relacion([sujeto(['Moreover,', the, peroxidation, of, polyunsaturated, fatty, acids]), verbo([leads]), complemento([to, the, formation, of, 'aldehydes,', which, can, act, as, toxic, 'by-products'])]). relacion([sujeto(['A', key, marker, of, lipid, 'peroxidation,', 'HNE-protein', 'adducts,', were]), verbo([found]), complemento([to, be, elevated, in, brain, tissues, and, body, fluids, of, 'Alzheimer', 'disease,', 'Parkinson', 'disease,', 'Huntington', disease, and, amyotrophic, lateral, sclerosis, subjects, 'and/or', models, of, the, respective, 'age-related', neurodegenerative, diseases])]). relacion([sujeto(['Although', only, a, few, proteins, were, identified, as, common]), verbo([targets]), complemento([of, 'HNE', modification, across, all, these, listed, 'disorders,', a, high, overlap, of, these, proteins, occurs, concerning, the, alteration, of, common, 'pathways,', such, as, glucose, metabolism, or, mitochondrial, function, that, are, known, to, contribute, to, cognitive, decline])]). relacion([sujeto(['Within', this, 'context,', despite, the, different, etiological, and, pathological, mechanisms, that]), verbo([lead]), complemento([to, the, onset, of, different, neurodegenerative, 'diseases,', the, formation, of, 'HNE-protein', adducts, might, represent, the, shared, 'leit-motif,', which, aggravates, brain, damage, contributing, to, disease, specific, clinical, presentation, and, decline, in, cognitive, performance, observed, in, each, case])]). relacion([sujeto(['Biglycan,', a, small, 'leucine-rich', 'proteoglycan,']), verbo([has]), complemento([been, shown, to, play, an, important, role, in, stabilizing, fibrotic, scars, after, experimental, myocardial, infarction])]). relacion([sujeto(['Left', ventricular, pressure, overload]), verbo([induced]), complemento([by, transverse, aortic, constriction, '(', 'TAC)', in, mice, resulted, in, left, ventricular, 'dysfunction,', fibrosis, and, increased, biglycan, expression])]). relacion([sujeto(['Biglycan', ablation, '(', 'KO)']), verbo([enhanced]), complemento([functional, recovery, but, did, not, resolve, cardiac, fibrosis])]). relacion([sujeto(['In', 'vitro,', biglycan]), verbo([induced]), complemento([hypertrophy, of, neonatal, rat, cardiomyocytes, and, led, to, activation, of, a, hypertrophic, gene, program])]). relacion([sujeto(['These', genes, were, concordantly]), verbo([induced]), complemento([by, 'TAC', in, 'WT', but, not, in, biglycan, 'KO', mice])]). relacion([sujeto(['Left', ventricular, pressure, overload]), verbo([induces]), complemento([biglycan, expression, in, cardiac, fibroblasts])]). relacion([sujeto(['In', vitro, biglycan]), verbo([induces]), complemento([hypertrophy, of, 'cardiomyocytes,', suggesting, that, biglycan, may, act, as, a, signaling, molecule, between, cell, types, to, modulate, cardiac, remodeling])]). relacion([sujeto(['Staphylococcal', infection, and, neutrophilic, inflammation, can]), verbo([act]), complemento([in, concert, to, establish, a, profoundly, hypoxic, environment])]). relacion([sujeto(['A', new, series, of, beta, amino, 'acids,', which]), verbo([act]), complemento([as, 'CXCR3', 'antagonists,', has, been, identified])]). relacion([sujeto(['Compounds', with, 'double-digit', nanomolar, 'CXCR3', 'affinity,', favourable, microsomal, stability, and, 'Caco-2', permeability]), verbo([have]), complemento([been, identified])]). relacion([sujeto(['In', many, 'ways,', social, media]), verbo([has]), complemento([transformed, the, practice, of, dietetics, and, has, opened, up, new, avenues, for, communicating, food, and, nutrition, information])]). relacion([sujeto(['Social', media]), verbo([has]), complemento([been, an, effective, tool, for, virtual, nutrition, 'counseling,', patient, 'education,', 'peer-to-peer', 'support,', and, public, health, campaigns])]). relacion([sujeto(['Increasingly,', nutrition, and, dietetics, practitioners, are, using, social, media, to, network, and, collaborate, with, 'colleagues,', conduct, a, job, 'search,', stay, current, with, new, 'research,', champion, a, 'cause,']), verbo([promote]), complemento([products, or, 'services,', and, build, a, business])]). relacion([sujeto(['In', 'addition,', it, is, critical, to]), verbo([have]), complemento([a, thorough, understanding, of, all, the, factors, related, to, social, media, 'professionalism,', including, disclosure, rules, from, the, 'Federal', 'Trade', 'Commission,', 'patient/client', privacy, and, confidentiality, as, covered, by, the, 'Health', 'Insurance', 'Portability', and, 'Accountability', 'Act,', and, copyright, laws, that, protect, intellectual, property])]). relacion([sujeto(['In', 'today\'s', digital, 'age,', it, is, essential, for, nutrition, and, dietetics, practitioners, to]), verbo([recognize]), complemento([the, professional, opportunities, and, challenges, of, social, media])]). relacion([sujeto(['Certain', violations, may]), verbo([have]), complemento([legal, implications])]). relacion([sujeto(['The', purpose, of, this, 'Academy', of, 'Nutrition', and, 'Dietetics', practice, paper, is, to]), verbo([provide]), complemento([guidance, on, social, 'media\'s', 'relevance,', potential, 'applications,', best, 'practices,', 'benefits,', and, risks])]). relacion([sujeto(['While', subepidermal, skin, inking, as, a, fashion, trend]), verbo([has]), complemento([rapidly, gained, popularity, in, 'Western', 'societies,', systemic, anaphylaxis, as, a, complication, of, tattooing, has, only, been, described, once, in, refereed, literature])]). relacion([sujeto(['Furthermore', the, previously]), verbo([reported]), complemento([case, was, from, a, patient, who, already, suffered, from, severe, allergies, and, no, attempt, to, pinpoint, the, actual, causes, was, made])]). relacion([sujeto(['Another', hour, later]), verbo([he]), complemento([appeared, in, the, emergency, room, with, a, grade, 3, systemic, anaphylaxis])]). relacion([sujeto(['He']), verbo([responded]), complemento([well, to, treatment, with, prednisolone, and, antihistamines])]). relacion([sujeto(['Further', workup, identified, 'formaldehyde,', 'nickel,', and, manganese, in, the, inks, as, potential, chemical]), verbo([triggers]), complemento([of, the, 'patient\'s', symptoms])]). relacion([sujeto(['Clinicians', should, be, alert, to, the, potential, capacity, of, tattoo, inks, to]), verbo([act]), complemento([as, triggers, of, systemic, anaphylaxis])]). relacion([sujeto(['Significant', illnesses, apart, from, the, acute, coronary, syndrome, are, important]), verbo([causes]), complemento([of, a, rise, in, cTn, to, above, the, 99, th, 'percentile,', and, appear, to, reflect, the, total, body, burden, of, disease])]). relacion([sujeto(['In', addition, to, their, role, in, correctly, attaching, specific, amino, acids, to, cognate, 'tRNAs,', 'aminoacyl-tRNA', synthetases, '(', 'aaRS)']), verbo([have]), complemento([been, found, to, possess, many, alternative, functions, and, often, bind, to, and, act, on, other, nucleic, acids])]). relacion([sujeto(['In', contrast, to, the, 'well-defined', 3, 'D', structure, of, 'tRNA,', the, structures, of, many, of, the, other, 'RNAs']), verbo([recognized]), complemento([by, aaRSs, have, not, been, solved])]). relacion([sujeto(['Despite', advances, in, the, use, of, 'X-ray', crystallography, '(', 'XRC),']), verbo([nuclear]), complemento([magnetic, resonance, '(', 'NMR)', spectroscopy, and, 'cryo-electron', microscopy, '(', 'cryo-EM)', for, structural, characterization, of, 'biomolecules,', significant, challenges, to, solving, 'RNA', structures, still, exist])]). relacion([sujeto(['Recently,', 'small-angle', 'X-ray', scattering, '(', 'SAXS)']), verbo([has]), complemento([been, increasingly, employed, to, characterize, the, 3, 'D', structures, of, 'RNAs', and, 'RNA-protein', complexes])]). relacion([sujeto(['SAXS', is, capable, of]), verbo([providing]), complemento(['low-resolution', tertiary, structure, information, under, physiological, conditions, and, with, less, intensive, sample, preparation, and, data, analysis, requirements, than, 'XRC,', 'NMR', and, 'cryo-EM'])]). relacion([sujeto(['In', this, 'article,', we, describe, best, practices]), verbo([involved]), complemento([in, the, process, of, 'RNA', and, 'RNA-protein', sample, 'preparation,', 'SAXS', data, 'collection,', data, 'analysis,', and, structural, model, building])]). relacion([sujeto(['Entirely', differing, from, the, common, 'templating-based', multistep, strategy, for, fabricating, multifunctional, hollow, mesoporous, silica, nanoparticles, '(', 'HMSN),', a, facile, and, 'template-free', synthetic, strategy]), verbo([has]), complemento([been, established, to, construct, a, unique, 'hollow/mesoporous', organosilica, nanocapsule, '(', 'OSNC)', concurrently, encapsulating, both, isopentyl, acetate, '(', 'PeA)', liquid, and, superparamagnetic, iron, oxides, inside, '(', denoted, as, 'PeA@OSNC)'])]). relacion([sujeto(['The', 'oil-phase', 'PeA', with, relatively, low, boiling, point, '(', 142, °, 'C)', and, high, volatility, not, only, plays, a, crucial, role, in, formation, of, a, large, hollow, cavity, from, the, viewpoint, of, structural, design, but, also, enables, the, 'PeA@OSNC', to]), verbo([act]), complemento([as, an, efficient, enhancement, agent, in, 'high-intensity', focused, ultrasound, '(', 'HIFU)', therapy])]). relacion([sujeto(['More', 'importantly,', such, a, novel, theranostic, agent]), verbo([has]), complemento([favorable, 'biosafety,', which, is, very, promising, for, future, clinical, application, in, 'MRI-guided', 'HIFU', therapy])]). relacion([sujeto(['Diabetes']), verbo([induces]), complemento([a, decrease, in, the, number, and, function, of, different, 'pro-angiogenic', cell, types, generically, designated, as, putative, endothelial, progenitor, cells, '(', 'EPC),', which, encompasses, cells, from, myeloid, origin, that, act, in, a, paracrine, fashion, to, promote, angiogenesis, and, putative, &, 'quot;true"', 'EPC', that, contribute, to, endothelial, replacement])]). relacion([sujeto(['Hyperglycemia,', insulin, resistance, and, dyslipidemia]), verbo([promote]), complemento([putative, 'EPC', dysregulation, by, affecting, the, 'SDF-1/CXCR-4', and, 'NO', pathways, and, the, 'p53/SIRT1/p66Shc', axis, that, contribute, to, their, 'mobilization,', 'migration,', homing, and, vasculogenic, properties])]). relacion([sujeto(['Among', 'them,', mobilizing, therapies, based, on, 'G-CSF,', erythropoietin, or, 'CXCR-4', antagonism]), verbo([have]), complemento([been, developed, to, increase, putative, 'EPC', number, to, treat, ischemic, diseases, with, or, without, prior, cell, isolation, and, transplantation])]). relacion([sujeto(['Moreover,', pharmacological, agents]), verbo([increasing]), complemento([in, vivo, the, bioavailability, of, 'NO', and, other, endothelial, factors, demonstrated, beneficial, effects, on, neovascularization, in, diabetic, ischemic, models, but, their, effects, on, endothelial, dysfunction, remain, poorly, evaluated])]). relacion([sujeto(['More', experiments, are, warranted, to, develop, orally, available, drugs, and, specific, agents]), verbo([targeting]), complemento([p66Shc, to, reverse, putative, 'EPC', dysfunction, in, the, expected, goal, of, preventing, endothelial, dysfunction, and, diabetic, cardiovascular, complications])]). relacion([sujeto(['The', standard, of, 5, -, 'Hydroxymethylfurfural', '(', 5, -, 'HMF)', existed, in, dextrose, injection, as, an, inevitable, 'by-product', during, 'high-temperature', setrilization]), verbo([has]), complemento([been, included, in, pharmacopoeias, considering, its, hazardous, effects, on, human, health])]). relacion([sujeto(['We']), verbo([found]), complemento([that, the, concentrations, of, 5, -, 'HMF', in, some, traditional, 'Chinese', medicine, injections, '(', 'TCMIs)', far, exceeded, its, limit, in, dextrose, injection])]). relacion([sujeto(['We']), verbo([found]), complemento([that, 5, -, 'HMF', increased, the, production, of, 'IgG2a', and, 'IFN-γ', when, 'co-injected', with, 'TNP-OVA,', indicating, its, capability, of, providing, a, 'co-stimulatory', signal, to, evoke, a, typical, 'type-1', immune, response])]). relacion([sujeto(['Compared', with, the, 5, -, 'HMF,', 'OMBF', elevated, the, production, of, 'IgG1,', 'IgG2,', 'IL-4', and, 'IFN-γ', in, response, to, both, reporter, 'antigens,']), verbo([suggesting]), complemento([that, 'OMBF', can, act, as, a, 'neo-antigen', or, 'neo-epitope', to, elicit, a, mixed, 'type-1', and, 'type-2', immune, response])]). relacion([sujeto(['It', indicates, that, both, 5, -, 'HMF', and, 'OMBF']), verbo([have]), complemento([immunosensitizing, potential, with, different, 'mechanisms,', and, exposure, to, 5, -, 'HMF', and, 'OMBF', may, represent, a, safety, concern, for, humans])]). relacion([sujeto(['Why', do, people]), verbo([act]), complemento(['altruistically?', 'One', theory, is, that, empathy, is, a, driver, of, morality])]). relacion([sujeto(['In', the, present, study, we, investigated, whether, empathy, traits, predict, if, people, will]), verbo([act]), complemento([altruistically, in, a, 'real-world', 'setting,', &, 'quot;in', the, 'wild"'])]). relacion([sujeto(['This', supports, the, theory, that, the]), verbo([act]), complemento([of, doing, good, is, correlated, with, empathy])]). relacion([sujeto(['There', is, demand, for, 'non-dimethyl', sulfoxide, '(', 'DMSO)', cryoprotective, agents, that]), verbo([maintain]), complemento([cell, viability, without, causing, poor, postthaw, function, or, systemic, toxicity])]). relacion([sujeto(['The', focus, of, this, investigation]), verbo([involves]), complemento([expanding, our, understanding, of, multicomponent, osmolyte, solutions, and, their, ability, to, preserve, cell, viability, during, freezing])]). relacion([sujeto(['Postthaw', recovery, of, mesenchymal, stem, cells, '(', 'MSCs)', in, solutions, containing, multiple, osmolytes]), verbo([have]), complemento([been, shown, to, be, comparable, or, better, than, that, of, 'MSCs', frozen, in, 10, '%', 'DMSO', at, 1, °, 'C/min', when, the, solution, composition, is, optimized])]). relacion([sujeto(['Raman', images, demonstrate, large, ice, crystal, formation, in, cryopreserved, cells, incubated, for, shorter, periods, of, time, '(', '∼30', 'min),']), verbo([suggesting]), complemento([that, longer, permeation, times, are, needed, for, these, solutions])]). relacion([sujeto(['Phase', change, behavior, '(', solidification, patterns, and, 'glass-forming', 'tendency)', did, not, differ, for, solutions, with, similar, 'osmolarity,', but, differences, in, postthaw, recovery]), verbo([suggest]), complemento([that, 'biological,', not, 'physical,', methods, of, protection, are, at, play])]). relacion([sujeto(['Taken', 'together,', the, information, from, these, studies]), verbo([increases]), complemento([our, understanding, of, 'non-DMSO', multicomponent, cryoprotective, solutions, and, the, manner, by, which, they, enhance, postthaw, recovery])]). relacion([sujeto(['Sensitivity', to, the, rewarding, properties, of, appetitive, substances]), verbo([has]), complemento([long, been, implicated, in, excessive, consumption, of, palatable, foods, and, drugs, of, abuse])]). relacion([sujeto(['Previous', research, focusing, on, individual, differences, in, reward, responsiveness]), verbo([has]), complemento([found, heightened, trait, reward, sensitivity, to, be, associated, with, 'binge-eating,', hazardous, 'drinking,', and, illicit, substance, use])]). relacion([sujeto(['Food', addiction]), verbo([has]), complemento([been, proposed, as, an, extreme, form, of, 'compulsive-overeating', and, has, been, associated, with, genetic, markers, of, heightened, reward, responsiveness])]). relacion([sujeto(['However,', little, research]), verbo([has]), complemento([explicitly, examined, the, association, between, reward, sensitivity, and, food, addiction])]). relacion([sujeto(['Further,', the, processes, by, which, individual, differences, in, this, trait, are]), verbo([associated]), complemento([with, excessive, 'over-consumption', has, not, been, determined])]). relacion([sujeto(['High', reward, sensitivity, was, significantly]), verbo([associated]), complemento([with, greater, food, addiction, symptoms, '(', 'r = 0'])]). relacion([sujeto(['Bootstrapped', tests, of, indirect, effects]), verbo([found]), complemento([the, relationship, between, reward, sensitivity, and, food, addiction, symptom, count, to, be, uniquely, mediated, by, 'binge-eating,', emotional, 'eating,', and, hedonic, eating, '(', 'notably,', food, 'availability)'])]). relacion([sujeto(['That', the, hedonic, properties, of, food, '(', especially, food, 'availability),', 'emotional,', and, 'binge-eating', behavior]), verbo([act]), complemento([as, unique, mediators, suggest, that, interventions, for, 'reward-sensitive', women, presenting, with, food, addiction, may, benefit, from, targeting, food, availability, in, addition, to, management, of, negative, affect])]). relacion([sujeto(['These', 'nano-drugs']), verbo([act]), complemento([as, robust, 'immune-suppressors,', affecting, cytokines, secretion, and, diminishing, hemorrhage, and, edema])]). relacion([sujeto(['Several', 'tumor-promoting', 'Euphorbiaceae', diterpenes, are, known, to]), verbo([act]), complemento([as, direct, activators, of, 'PKC,', but, many, types, of, such, diterpenes, have, not, been, studied, as, platelet, stimulators])]). relacion([sujeto(['The', investigated, phorbol, esters, and, ingenane, esters]), verbo([induced]), complemento([blood, platelet, aggregation, and, 'ATP', secretion])]). relacion([sujeto(['PKC', activation, was, demonstrated, by]), verbo([inducing]), complemento([membrane, translocation, of, 'PKCs,', phosphorylation, of, 'PKC', 'substrates,', and, activation, of, 'PKC', signaling, pathways])]). relacion([sujeto(['The', 'PKC-activating', effect, of, the, compounds, correlated, well, with, their, efficacy, to]), verbo([cause]), complemento([platelet, stimulation])]). relacion([sujeto(['Moreover,', by, using, an, 'isoform-specific', 'PKC', 'inhibitor,', it, was]), verbo([found]), complemento([that, besides, conventional, 'PKCs', novel, 'PKCs', also, play, a, positive, role, in, platelet, activation, caused, by, 'phorbol/ingenane', 'esters,', especially, in, regulating, platelet, aggregation])]). relacion([sujeto(['The', present, results]), verbo([suggest]), complemento([that, platelets, afford, a, useful, model, for, studying, 'PKC', activators, of, natural, origin, or, their, chemical, derivatives])]). relacion([sujeto(['Here', we]), verbo([report]), complemento([that, retinoic, acid, '(', 'RA)', or, retinol, '(', vitamin, 'A)', and, ascorbate, '(', vitamin, 'C)', act, as, modulators, of, 'TET', levels, and, activity])]). relacion([sujeto(['RA', or, retinol]), verbo([enhances]), complemento([5, hmC, production, in, naïve, embryonic, stem, cells, by, activation, of, 'TET2', and, 'TET3', 'transcription,', whereas, ascorbate, potentiates, 'TET', activity, and, 5, hmC, production, through, enhanced, 'Fe(2+)', 'recycling,', and, not, as, a, cofactor, as, reported, previously])]). relacion([sujeto(['We']), verbo([find]), complemento([that, both, ascorbate, and, 'RA', or, retinol, promote, the, derivation, of, induced, pluripotent, stem, cells, synergistically, and, enhance, the, erasure, of, epigenetic, memory])]). relacion([sujeto(['This', mechanistic, insight]), verbo([has]), complemento([significance, for, the, development, of, cell, treatments, for, regenenerative, 'medicine,', and, enhances, our, understanding, of, how, intrinsic, and, extrinsic, signals, shape, the, epigenome])]). relacion([sujeto(['Strong', social, capital, is, increasingly]), verbo([recognized]), complemento([as, an, organizational, advantage])]). relacion([sujeto(['Better', knowledge, sharing, and, reduced, transaction, costs]), verbo([increase]), complemento([work, efficiency])]). relacion([sujeto(['To', mimic, the, formation, of, the]), verbo([associated]), complemento([communication, 'network,', we, propose, the, 'Expert', 'Game,', where, each, individual, must, find, a, specific, expert, and, receive, her, help])]). relacion([sujeto(['Participants']), verbo([act]), complemento([in, an, impersonal, environment, and, under, time, constraints, that, provide, 'short-term', incentives, for, noncooperative, behavior])]). relacion([sujeto(['Despite', these, 'constraints,', we, observe, cooperation, between, individuals, and, the, 'self-organization', of, a, sustained, trust, 'network,', which, facilitates, efficient, communication, channels, with]), verbo([increased]), complemento([information, flow])]). relacion([sujeto(['Analysis', of, the, model]), verbo([reveals]), complemento([an, exploitation, protection, mechanism, and, measurable, social, 'capital,', which, quantitatively, describe, the, economic, utility, of, trust])]). relacion([sujeto(['Scorpion', envenomation, is, a, common, event, in, many, tropical, and, subtropical, 'countries,', with, neuropharmacological, 'actions,', particularly, autonomic, nervous, system, 'modulation,']), verbo([causing]), complemento([significant, mortality])]). relacion([sujeto(['The', identification, and, functional, characterisation, of, these, 'SCTX', peptides]), verbo([has]), complemento([tremendous, potential, for, development, of, novel, pharmaceuticals, that, advance, knowledge, of, ion, channels, and, establish, lead, compounds, for, treatment, of, excitable, tissue, disorders])]). relacion([sujeto(['This', review, delineates, the, unique, specificities, of, 320, individual, 'SCTX', peptides, that, collectively]), verbo([act]), complemento([on, 41, ion, channel, subclasses])]). relacion([sujeto(['Thus', the, 'SCTX', research, field]), verbo([has]), complemento([significant, translational, implications, for, pathophysiology, spanning, 'neurotransmission,', neurohumoral, 'signalling,', 'sensori-motor', systems, and, 'excitation-contraction', coupling])]). relacion([sujeto(['High-frequency', temperature, fluctuations]), verbo([caused]), complemento([no, deviations, from, typical, coevolutionary, arms, race, dynamics])]). relacion([sujeto(['Temperature', variation, affected, population, 'density,']), verbo([providing]), complemento([evidence, that, 'eco-evolutionary', feedbacks, act, through, variable, 'bacteria-phage', encounter, rates])]). relacion([sujeto(['Whether', coevolution, persists, or, stalls, depends, on, the, frequency, of, change, and, the, environmental, optima, of, both]), verbo([interacting]), complemento([players])]). relacion([sujeto(['A', combination, of, nickel, and, photoredox, catalysts]), verbo([promoted]), complemento([novel, 'cross-coupling', reactions, of, aryl, halides, with, 4, -, 'alkyl-1,4-dihydropyridines'])]). relacion([sujeto([4, -, 'Alkyl-1,4-dihydropyridines']), verbo([act]), complemento([as, formal, nucleophilic, alkylation, reagents, through, a, 'photoredox-catalyzed', 'carbon-carbon', '(', 'C-C)', 'bond-cleavage', process])]). relacion([sujeto(['The', present, strategy]), verbo([provides]), complemento([an, alternative, to, classical, 'carbon-centered', 'nucleophiles,', such, as, organometallic, reagents])]). relacion([sujeto(['Their', expression, is, restricted, adaxially, during, early, development, by, the, abaxially]), verbo([expressed]), complemento([microRNA, '(', 'MIR)165/166,', yet, the, mechanism, that, restricts, 'MIR165/166', expression, to, abaxial, leaf, tissues, remains, unknown])]). relacion([sujeto(['Here,', we, show, that, class, 'III', and, class, 'II', 'HD-ZIP', proteins]), verbo([act]), complemento([together, to, repress, 'MIR165/166', via, a, conserved, 'cis-element', in, their, promoters])]). relacion([sujeto(['Organ', morphology, and, tissue, patterning, in, 'plants,', 'therefore,', depend, on, a, bidirectional, repressive, circuit]), verbo([involving]), complemento([a, set, of, miRNAs, and, its, targets])]). relacion([sujeto(['Aromatase', inhibitors, '(', 'AIs)', are, a, class, of, drugs, that]), verbo([act]), complemento([by, blocking, the, production, of, estrogens, from, androgens])]). relacion([sujeto(['Morphological', anomalies, noted, in, fetuses, exposed, to, 'AIs', included, skeletal, 'anomalies,', abnormal, head, 'morphology,']), verbo([increased]), complemento(['ano-genital', distance, in, female, 'fetuses,', and, minor, urinary, tract, system, anomalies])]). relacion([sujeto(['Placental', enlargement, was, consistently]), verbo([reported]), complemento([in, rats, and, 'non-human', primates, after, maternal, treatment, with, several, 'AIs'])]). relacion([sujeto(['In', 'conclusion,', data, from, basic, scientific, research]), verbo([suggest]), complemento([that, low, intensity, exposure, to, 'AIs', applied, during, a, wide, gestational, window, can, profoundly, affect, prenatal, development])]). relacion([sujeto(['Current', research, supports, the, notion, that, the, apparently, innate, trait, 'Sensory', 'Processing', 'Sensitivity', '(', 'SPS)', may]), verbo([act]), complemento([as, a, modulator, of, development, as, function, of, the, environment])]). relacion([sujeto(['While', neural, mechanisms, underlying, 'SPS', are, largely, 'unknown,', those]), verbo([associated]), complemento([with, the, 5, -, 'HTTLPR', have, been, extensively, investigated])]). relacion([sujeto(['We', perform, a, comparative, analysis, of, research, findings, on, sensory, processing, facets]), verbo([associated]), complemento([with, the, trait, and, polymorphism, 'to:', 1])]). relacion([sujeto(['Trait', and, polymorphism, are, both]), verbo([associated]), complemento([with, differential, susceptibility, to, environmental, 'stimuli;', 'additionally,', both, involve, 1])]). relacion([sujeto(['FT', showed, superior, activity, of]), verbo([inhibiting]), complemento(['NO', production, of, 'RAW264'])]). relacion([sujeto([7, cells]), verbo([induced]), complemento([by, lipopolysaccharide, '(', 'LPS)', in, the, preliminary, biological, screening])]). relacion([sujeto(['More', 'meaningful,', 'FT', could, 'down-regulate', the, expression, of, 'cyclooxygenase-2', '(', 'COX-2)', and]), verbo([decrease]), complemento([the, expressions, of, 'pro-inflammatory', 'cytokines,', tumor, necrosis, 'factor-α', '(', 'TNF-α),', 'interleukin-6', '(', 'IL-6)', and, 'interleukin-1β', '(', 'IL-1β),', in, both, gene, and, protein, levels])]). relacion([sujeto(['In', mechanism, 'study,', 'FT', blocked, the, 'LPS-induced', upregulation, of]), verbo([phosphorylated]), complemento(['phosphoinositide-3-kinase', and, 'Akt', '(', 'PI3K/Akt)'])]). relacion([sujeto(['Furthermore,', 'FT']), verbo([inhibited]), complemento([the, translocation, of, nuclear, 'factor-kappa', 'B', '(', 'NF-κB)', through, the, prevention, of, inhibitory, factor, kappa, 'B', alpha, '(', 'IκBα)', phosphorylation, and, degradation, and, also, suppressed, the, 'mitogen-activated', protein, kinases, '(', 'MAPK)', signaling, pathway, in, 'LPS-stimulated', 'RAW264'])]). relacion([sujeto(['In', 'addition,', 'FT', upregulated, heme, 'oxygenase-1', '(', 'HO-1)', expression, via]), verbo([nuclear]), complemento([translocation, of, nuclear, factor, 'E2-related', factor, 2, '(', 'Nrf2)'])]). relacion([sujeto(['Taken', 'together,', 'FT', might]), verbo([act]), complemento([as, a, natural, agent, to, treat, some, inflammatory, diseases, by, targeting, 'PI3K/Akt,', 'MARK', and, 'Nrf2/HO-1', pathways])]). relacion([sujeto(['The', abnormal, expression, of, the, long, noncoding, 'RNA', metastasis]), verbo([associated]), complemento([lung, adenocarcinoma, transcript, 1, '(', 'MALAT1)', or, 'miR-200', family, members, were, shown, to, facilitate, 'EMT', in, multiple, human, 'cancers,', but, the, regulatory, mechanism, by, which, 'MALAT1', and, 'miR-200', act, remains, unknown])]). relacion([sujeto(['Previous', studies]), verbo([have]), complemento([shown, that, 'miR-200', family, members, are, enriched, in, 'EEC', as, well, as, melanoma, and, some, ovarian, carcinomas])]). relacion([sujeto(['Moreover,', we]), verbo([found]), complemento([that, 'miR-200c', bound, directly, to, 'MALAT1', using, luciferase, reporter, and, 'qRT-PCR', assays])]). relacion([sujeto(['MALAT1', and, 'miR-200c', are, reciprocally, 'repressed,', and, 'TGF-β']), verbo([increased]), complemento(['MALAT1', expression, by, inhibiting, 'miR-200c'])]). relacion([sujeto(['When', the, interaction, between, 'miR-200c/MALAT1', was, 'interrupted,', the, invasive, capacity, of, 'EEC', cells, was]), verbo([decreased]), complemento([and, 'EMT', markers, expression, were, altered, 'in vitro'])]). relacion([sujeto(['A', xenograft, tumor, model, was, used, to, show, that]), verbo([targeting]), complemento([the, 'miR-200c/MALAT1', axis, inhibited, 'EEC', growth, and, 'EMT-associated', protein, expression, 'in vivo'])]). relacion([sujeto(['In', 'summary,', 'miR-200c/MALAT1', axis, is, a]), verbo([target]), complemento([with, therapeutic, potential, in, 'EEC'])]). relacion([sujeto(['This', practice, primarily]), verbo([involves]), complemento([minors])]). relacion([sujeto(['We']), verbo([report]), complemento([the, cases, of, an, 11, -, 'year-old', and, a, 15, -, 'year-old', boy, examined, in, the, forensic, unit, at, the, 'Hôtel-Dieu', hospital, in, 'Paris,', after, their, father, complained, to, the, 'Minors', 'Protection', 'Brigade', of, 'Paris', following, the, discovery, of, their, circumcision])]). relacion([sujeto(['The', examination, conducted, in, the, forensic, unit]), verbo([found]), complemento([that, the, two, boys, had, undergone, recent, circumcision])]). relacion([sujeto(['Ritual', &, 'quot;medicalized"', circumcision, is, legal, in, 'France,', and, does, not, fall, under, 'article 222-1 of', the, 'Criminal', 'Code', '(', torture, and]), verbo([acts]), complemento([of, 'barbarism)', or, 'article 16-1 of', the, 'Civil', 'Code', '(', inviolability, of, the, human, 'body)'])]). relacion([sujeto(['Few', studies]), verbo([have]), complemento([attempted, to, characterize, how, 'co-occurring', risk, factors, for, substance, use, disorders, intersect])]). relacion([sujeto(['A', recent, study, examined, this, question, regarding, cigarette, smoking, and, demonstrated, that, 'co-occurring', risk, factors, generally]), verbo([act]), complemento([independently])]). relacion([sujeto(['Logistic', regression, and, classification, and, regression, tree, '(', 'CART)', modeling, were, used, to, examine, risk, of, 'past-year', drug, 'abuse/dependence']), verbo([associated]), complemento([with, a, 'well-established', set, of, risk, factors, for, substance, use, '(', 'age,', 'gender,', 'race/ethnicity,', 'education,', 'poverty,', smoking, 'status,', alcohol, 'abuse/dependence,', mental, 'illness)'])]). relacion([sujeto(['Each', of, these, risk, factors, was]), verbo([associated]), complemento([with, significant, increases, in, the, odds, of, drug, 'abuse/dependence', in, univariate, logistic, regressions])]). relacion([sujeto(['Here,', we]), verbo([report]), complemento([the, isolation, and, 'NMR-', and, 'MS-based', structure, elucidation, of, monoglycosylated, bartolosides, 'E-K', '(', 5, -, 11, ')', ',', obtained, from, 'Synechocystis', salina, 'LEGE', 6099, ',', a, strain, closely, related, to, the, cyanobacterium, that, produces, the, diglycosylated, 2, -, 4])]). relacion([sujeto(['Their', structures, and, the, organization, of, the, brt, genes]), verbo([suggest]), complemento([that, the, 'DAR-forming', ketosynthase, 'BrtD', can, generate, structural, diversity, by, accepting, fatty, 'acyl-derived', substrates, of, varying, length])]). relacion([sujeto(['Compound', 9, features, a, rare, midchain, 'gem-dichloro', 'moiety,', indicating, that, the, putative, halogenase, 'BrtJ', is, able, to]), verbo([act]), complemento([twice, on, the, same, midchain, carbon])]). relacion([sujeto([')', administration]), verbo([decreased]), complemento([the, severity, of, 'tonic-clonic', seizures])]). relacion([sujeto(['PEA']), verbo([has]), complemento([anticonvulsant, features, in, 'DBA/2', mice, mainly, through, 'PPAR-α', and, likely, indirectly, on, 'CB1', 'receptors,', whereas, 'ACEA', and, 'WIN', act, through, 'CB1', receptors])]). relacion([sujeto(['We']), verbo([found]), complemento([that, 'PEA,', 'ACEA', and, 'WIN', 'co-administration', potentiated, the, efficacy, of, 'carbamazepine,', 'diazepam,', 'felbamate,', 'gabapentin,', 'phenobarbital,', topiramate, and, valproate, and, 'PEA', only, also, that, of, oxcarbazepine, and, lamotrigine, 'whereas,', their, 'co-administration', with, levetiracetam, and, phenytoin, did, not, have, effects])]). relacion([sujeto(['In', 'conclusion,', 'PEA,', 'ACEA', and, 'WIN', show, anticonvulsant, effects, in, 'DBA/2', mice, and, potentiate, the, effects, several, 'AEDs']), verbo([suggesting]), complemento([a, possible, therapeutic, relevance, of, these, drugs, and, their, mechanisms, of, action])]). relacion([sujeto(['Despite', therapeutic, 'advances,', lung, cancer, remains, one, of, the, most, common]), verbo([causes]), complemento([of, 'cancer-related', deaths, worldwide])]). relacion([sujeto(['The', 'ZNF703', gene]), verbo([has]), complemento([been, identified, as, the, driver, of, the, 8, 'p11-12', region, and, its, amplification, or, overexpression, has, been, associated, with, several, types, of, cancers])]). relacion([sujeto(['It']), verbo([has]), complemento([also, been, shown, that, 'ZNF703', overexpression, can, activate, the, 'Akt/mTOR', signaling, pathway])]). relacion([sujeto(['Althogh', the, correlation, did, not, reach, a, statistically, significant, level, 'Akt', phosphorylation, was]), verbo([increased]), complemento([in, tumor, tissues, expressing, high, levels, of, 'ZNF703'])]). relacion([sujeto(['The', role, of, the, 'ZNF703', gene]), verbo([has]), complemento([not, been, investigated, in, 'NSCLC'])]). relacion([sujeto(['Our', data, show, that, 'ZNF703', may, contribute, to, tumor, development, in, 'NSCLC', by]), verbo([activating]), complemento([the, 'Akt/mTOR', pathway])]). relacion([sujeto(['Carotenoids', and, retinoids]), verbo([have]), complemento([several, similar, biological, activities, such, as, antioxidant, 'properties,', the, inhibition, of, malignant, tumour, growth, and, the, induction, of, apoptosis])]). relacion([sujeto(['Supplementation', with, carotenoids, can, affect, cell, growth, and]), verbo([modulate]), complemento([gene, expression, and, immune, responses])]). relacion([sujeto(['Epidemiological', studies]), verbo([have]), complemento([shown, a, correlation, between, a, high, carotenoid, intake, in, the, diet, with, a, reduced, risk, of, 'breast,', 'cervical,', 'ovarian,', colorectal, 'cancers,', and, cardiovascular, and, eye, diseases])]). relacion([sujeto(['Cancer', chemoprevention, by, dietary, carotenoids]), verbo([involves]), complemento([several, 'mechanisms,', including, effects, on, gap, junctional, intercellular, 'communication,', growth, factor, 'signalling,', cell, cycle, 'progression,', 'differentiation-related', 'proteins,', 'retinoid-like', 'receptors,', antioxidant, response, 'element,', nuclear, 'receptors,', 'AP-1', transcriptional, 'complex,', the, 'Wnt/β-catenin', pathway, and, inflammatory, cytokines])]). relacion([sujeto(['Moreover,', carotenoids, can]), verbo([stimulate]), complemento([the, proliferation, of, 'B-', and, 'T-lymphocytes,', the, activity, of, macrophages, and, cytotoxic, 'T-cells,', effector, 'T-cell', function, and, the, production, of, cytokines])]). relacion([sujeto(['Recently,', the, beneficial, effects, of, 'carotenoid-rich', vegetables, and, fruits, in, health, and, in]), verbo([decreasing]), complemento([the, risk, of, certain, diseases, has, been, attributed, to, the, major, 'carotenoids,', 'β-carotene,', 'lycopene,', 'lutein,', 'zeaxanthin,', crocin, '(', /, 'crocetin)', and, 'curcumin,', due, to, their, antioxidant, effects])]). relacion([sujeto(['It', is, thought, that, carotenoids]), verbo([act]), complemento([in, a, 'time-', and, 'dose-dependent', manner])]). relacion([sujeto(['Adherent', 'pathogen-associated', molecular, patterns, '(', 'PAMPs),', of, which, 'LPS', is, the, 'best-studied', and, classical, endotoxin, produced, by, 'Gram-negative', 'bacteria,']), verbo([act]), complemento([to, increase, the, biological, activity, of, osteopedic, wear, particles, such, as, 'polymethyl-methacrylate', '(', 'PMMA)', and, titanium, particles, in, cell, culture, and, animal, models, of, implant, loosening])]). relacion([sujeto(['The', levels, of, inflammatory, mediators, including, tumour, necrosis, 'factor-α', '(', 'TNF-α),', 'matrixmetallo-proteinases-9', '(', 'MMP-9)', and, 'interleukin-6', '(', 'IL-6),', receptor, activation, of]), verbo([nuclear]), complemento([factor, 'NF-κB', '(', 'RANK),', and, cathepsin, 'K', were, examined, and, the, amounts, of, phosphorylated, 'I-κB,', 'MEK,', 'JNK', and, p38, were, measured])]). relacion([sujeto(['Our', results, showed, that, 'UTI', pretreatment]), verbo([suppressed]), complemento([the, secretion, of, proinflammatory, cytokines, including, 'MMP-9,', 'IL-6,', 'TNF-α,', 'RANK', and, cathepsin, 'K', through, 'down-regulating', the, activity, of, nuclear, factor, kappa, 'B', '(', 'NF-κB)', and, 'MAPKs', partly, in, 'LPS/PMMA-mediated', 'Raw264'])]). relacion([sujeto(['Finally,', 'UTI', treatment]), verbo([decreased]), complemento([the, inflammatory, osteolysis, reaction, in, 'PMMA-induced', murine, osteolysis, models])]). relacion([sujeto(['MicroRNAs', '(', 'miRNAs)', are, small, 'non-coding', 'RNAs', which, can]), verbo([act]), complemento([as, master, regulators, of, gene, 'expression,', modulate, almost, all, biological, process, and, are, essential, for, maintaining, cellular, homeostasis])]). relacion([sujeto(['Dysregulation', of, miRNA, expression]), verbo([has]), complemento([been, associated, with, aberrant, gene, expression, and, may, lead, to, pathological, conditions])]). relacion([sujeto(['Evidence']), verbo([suggests]), complemento([that, miRNA, expression, profiles, are, altered, between, health, and, disease, and, as, such, may, be, considered, as, biomarkers, of, disease])]). relacion([sujeto(['Evidence', is]), verbo([increasing]), complemento([that, miRNAs, are, particularly, important, in, lung, homeostasis, and, development, and, have, been, demonstrated, to, be, the, involved, in, many, pulmonary, diseases, such, as, 'asthma,', 'COPD,', 'sarcoidosis,', lung, cancer, and, other, smoking, related, diseases])]). relacion([sujeto(['Recently,', some, 'miRNA-based', drugs]), verbo([have]), complemento([been, introduced, as, possible, therapeutic, agents])]). relacion([sujeto(['Although', 'Endo-M']), verbo([has]), complemento([been, known, to, act, on, various, 'N-glycans,', it, does, not, act, on, 'core-fucosylated', 'N-glycans,', which, exist, widely, in, mammalian, 'glycoproteins,', thus, limiting, its, application])]). relacion([sujeto(['Therefore,', we, performed, 'site-directed', mutagenesis, on, 'Endo-M', to, isolate, mutant, enzymes, that, are, able, to]), verbo([act]), complemento([on, 'mammalian-type', 'core-α1,6-fucosylated', glycans])]). relacion([sujeto(['Such', mutant, enzymes, exhibited]), verbo([increased]), complemento([hydrolysis, of, a, synthetic, 'α1,6-fucosylated', trimannosyl, core, 'structure,', whereas, their, activity, on, the, afucosylated, form, decreased])]). relacion([sujeto(['W251N', mutants, could]), verbo([act]), complemento([on, the, immunoglobulin, 'G-derived', 'core-fucosylated', glycopeptides, and, human, lactoferrin, glycoproteins])]). relacion([sujeto(['This', mutant, was, also, capable, of, transferring, the, sialyl, glycan, from, an]), verbo([activated]), complemento([substrate, intermediate, '(', sialyl, 'glyco-oxazoline)', onto, an, 'α1,6-fucosyl-N-acetylglucosaminyl', biotin])]). relacion([sujeto(['Furthermore,', the, 'W251N', mutant, gained, a, 'glycosynthase-like', activity, when, a, 'N175Q', substitution, was, introduced, and, it]), verbo([caused]), complemento([accumulation, of, the, transglycosylation, products])]). relacion([sujeto(['A', 'Cross', 'Company', 'Abuse', 'Liability', 'Council', '(', 'CCALC)', was, formed, during, the, process, of, this, unique, collaborative, effort, between, 'Industry', and, 'Federal', 'Regulators', whose, goals, were, to, establish, the, development, of, standards, for, the, preclinical, screening, of, new, molecular, entities, for, schedule, control, actions]), verbo([required]), complemento([as, part, of, every, 'New', 'Drug', 'Application', process])]). relacion([sujeto(['In', a, series, of, recent, 'pre-study', protocol, reviews, requested, by, confidential, 'Pharmaceutical', 'Sponsors', of, 'MPI', 'Research,', the, 'CSS', staff, appeared, to, change, its, policy, and, set, forth, to]), verbo([require]), complemento([all, drug, discrimination, study, data, to, be, generated, under, &, 'quot;extinction"', test, sessions])]). relacion([sujeto(['MPI', 'Research', is, a, 'Contract', 'Research', 'Organization']), verbo([acting]), complemento([on, behalf, of, pharmaceutical, companies, and, bound, under, separate, confidentiality, agreements])]). relacion([sujeto(['At', the, end, of, the, 'follow-up', 'period,', treated, patients, showed, significantly, less, immune, activation, and, lower, regulatory, 'T-cell', 'counts,', with, an]), verbo([increased]), complemento(['Th17', and, 'Th1', response])]). relacion([sujeto(['This', randomised, pilot, clinical, trial, administering, benznidazole, to, patients, with, indeterminate, chronic, 'Chagas', disease, brings, about, changes, in, the, adaptive, 'immunity,']), verbo([leading]), complemento([to, a, general, decrease, in, inflammatory, status])]). relacion([sujeto(['This', apparently, beneficial, response, could]), verbo([act]), complemento([as, the, basis, for, monitoring, new, antiparasitic, drugs])]). relacion([sujeto(['Mhg,', a, typical, 'α/β', fold, 'hydrolase,', was, previously]), verbo([reported]), complemento([to, have, both, 'γ-lactamase', and, perhydrolase, activities])]). relacion([sujeto(['Molecular', docking, and, sequence, analysis]), verbo([suggested]), complemento([a, possible, role, for, the, entry, of, the, binding, pocket, in, blocking, the, entrance, 'tunnel,', preventing, the, ester, compounds, from, entering, into, the, pocket])]). relacion([sujeto(['Site', 233, at, the, entrance, tunnel, of, 'Mhg', was]), verbo([found]), complemento([to, play, a, pivotal, role, in, modulating, the, three, catalytic, activities, by, adjusting, the, size, and, shape, of, the, 'tunnel,', with, different, amino, acid, substitutions, at, this, site, facilitating, different, activities])]). relacion([sujeto(['Considering', the, amino, acid, conservation, and, 'differentiation,', this, site, could, be, a, key]), verbo([target]), complemento([for, future, protein, engineering])]). relacion([sujeto(['In', 'addition,', we, demonstrate, that, engineering, the, entrance, tunnel, is, an, efficient, strategy, to]), verbo([regulate]), complemento([enzyme, catalytic, capabilities])]). relacion([sujeto(['Promiscuous', enzymes, can]), verbo([act]), complemento([as, starting, points, in, the, evolution, of, novel, catalytic, 'activities,', thus, providing, a, molecular, basis, for, the, production, of, new, biological, functions])]). relacion([sujeto(['We']), verbo([found]), complemento([that, substitution, of, this, residue, with, smaller, amino, acids, such, as, 'Gly,', 'Ala,', 'Ser,', or, 'Pro', endowed, the, enzyme, with, novel, esterase, activity])]). relacion([sujeto(['Our', study]), verbo([has]), complemento([important, implications, for, the, regulation, of, enzyme, catalytic, promiscuity, and, development, of, protein, engineering, methodologies])]). relacion([sujeto(['The', potential, efficacy, of, cannabinoid, receptor, ligands, for, the, treatment, of, epilepsy, remains, 'controversial;', cannabis, components, that]), verbo([act]), complemento([via, cannabinoid, type, 1, '(', 'CB1)', receptors, produce, anticonvulsant, effects, in, animal, models, despite, treatment, with, the, 'CB', receptor, agonist, reliably, inducing, convulsions, in, various, species])]). relacion([sujeto(['Moreover,', the, potential, role, of, cannabinoid, receptor, type, 2, '(', 'CB2)', to]), verbo([modulate]), complemento([seizures, remains, 'under-investigated'])]). relacion([sujeto(['AM1241', administration, significantly]), verbo([increased]), complemento(['tonic-clonic', seizure, incidence, and, severity, while, also, decreasing, the, onset, of, generalized, seizures, '(', 'AM1241', 1, and, 10, 'μg/2μl)'])]). relacion([sujeto(['Pretreatment', with, 'AM630']), verbo([prevented]), complemento([the, proconvulsant, effects, of, 'AM1241'])]). relacion([sujeto(['This', study, 'shows,', for, the, first, 'time,', that, selective, activation, of, 'CB2', receptors, can]), verbo([increase]), complemento([generalized, seizure, susceptibility, and, suggests, that, pathological, hyperexcitability, phenomena, can, be, differentially, regulated, by, targeting, 'CB1', and, 'CB2', receptors])]). relacion([sujeto(['They']), verbo([provide]), complemento([the, advantage, of, small, 'size,', short, serum, 'half-life,', and, lack, of, effector, function])]). relacion([sujeto(['Several', proteases]), verbo([associated]), complemento([with, invasive, diseases, are, known, to, cleave, antibodies, in, the, 'hinge-region,', and, this, results, in, 'anti-hinge', antibodies, '(', 'AHA)', toward, the, neoepitopes])]). relacion([sujeto(['The', 'AHA', can]), verbo([act]), complemento([as, surrogate, 'Fc', and, reintroduce, the, properties, of, the, 'Fc', that, are, otherwise, lacking, in, antibody, fragments])]). relacion([sujeto(['In', our, 'study,', we, identify, a, truncation, in, the, lower, hinge, region, of, the, antibody, that]), verbo([maintains]), complemento([efficient, proteolytic, cleavage, by, 'IdeS', protease])]). relacion([sujeto(['The', resulting, neoepitope, at, the, 'F(ab\')2', 'C-terminus', does, not]), verbo([have]), complemento([detectable, binding, of, 'pre-existing', 'AHA,', providing, a, practical, route, to, produce, 'F(ab\')2', in, vitro, by, proteolytic, digestion, when, the, binding, of, 'pre-existing', 'AHA', is, undesired])]). relacion([sujeto(['We', extend, our, studies, to, the, upper, hinge, region, of, the, antibody, and]), verbo([provide]), complemento([a, detailed, analysis, of, the, contribution, of, 'C-terminal', residues, of, the, upper, hinge, of, human, 'IgG1,', 'IgG2', and, 'IgG4', to, 'pre-existing', 'AHA', reactivity, in, human, serum])]). relacion([sujeto(['Our', work, now, enables, the, production, of, 'Fab', and, 'F(ab\')2', for, therapeutic, and, diagnostic, immune, assays, that]), verbo([have]), complemento([minimal, reactivity, toward, 'pre-existing', 'AHA'])]). relacion([sujeto(['Visceral', leishmaniasis, '(', 'VL)', is, a, potentially, fatal, parasitic, disease]), verbo([associated]), complemento([with, 'fever,', cachexia, and, impaired, protective, 'T-cell', responses, against, the, parasite])]). relacion([sujeto(['An', expanded, population, of, 'low-density', neutrophils, that]), verbo([expressed]), complemento(['HLA-DR,', 'CD80', and, 'CD86', was, observed, in, subjects, with, 'VL'])]). relacion([sujeto(['Plasma', from, patients, with, acute, 'VL', was, able, to]), verbo([induce]), complemento([similar, 'high-level', 'HLA-DR', expression, in, neutrophils, from, healthy, subjects])]). relacion([sujeto(['HLA-DR(+)', neutrophils, from, subjects, with, 'VL', did, not]), verbo([stimulate]), complemento(['T-cell', 'proliferation,', but, they, did, express, higher, programmed, cell, death, 'ligand-1', '(', 'PDL1)', than, other, 'neutrophils,', and, lymphocytes, of, the, same, subjects, expressed, high, programmed, cell, death, 1, '(', 'PD1)'])]). relacion([sujeto(['Patients', with, acute, 'VL']), verbo([have]), complemento([expanded, circulating, 'low-density', neutrophils, expressing, markers, of, antigen, 'presentation,', which, diminish, after, treatment])]). relacion([sujeto(['Although', we]), verbo([found]), complemento([no, evidence, that, they, act, as, 'antigen-presenting', 'cells,', these, neutrophils, expressed, markers, implicating, a, role, in, 'T-cell', exhaustion])]). relacion([sujeto(['Fragile', 'X', syndrome, '(', 'FXS)', is, the, most, common]), verbo([cause]), complemento([of, inherited, intellectual, disability, and, autism])]). relacion([sujeto(['FXS', results, from, the, absence, of, 'FMRP,', an, 'RNA']), verbo([binding]), complemento([protein, associated, to, ribosomes, that, influences, the, translation, of, specific, mRNAs, in, 'post-synaptic', compartments, of, neurons])]). relacion([sujeto(['DAG', and, 'PA', are, two, interconvertible, lipids, that, influence, membrane, architecture, and, that]), verbo([act]), complemento([as, essential, signaling, molecules, that, activate, various, downstream, 'effectors,', including, master, regulators, of, local, protein, synthesis, and, actin, polymerization])]). relacion([sujeto(['The', deregulated, levels, of, 'DAG', and, 'PA']), verbo([caused]), complemento([by, the, absence, of, 'FMRP', could, represent, a, novel, therapeutic, target, for, the, treatment, of, 'FXS'])]). relacion([sujeto(['Through', comparison, of, free, 'RRM', domain, and, complex, 'systems,', 'it\'s']), verbo([found]), complemento([that, the, 'RNA', binding, facilitates, stabilizing, the, 'RNA-binding', interface, of, 'RRM', 'domain,', especially, the, 'C-terminal', loop])]). relacion([sujeto(['Although', both, 'R38Q', and, 'T103A/K104A', mutations, reduce, the]), verbo([binding]), complemento([affinity, of, 'RRM', domain, and, 'RNA,', the, underlining, mechanisms, are, different])]). relacion([sujeto(['R38Q', mutation, is, positioned, on, the, homodimerization, interface, and, mainly]), verbo([induces]), complemento([the, large, fluctuations, of, 'RRM', domains])]). relacion([sujeto(['This', mutation, does, not, directly]), verbo([act]), complemento([on, the, 'RNA-binding', 'interface,', but, some, interfacial, hydrogen, bonds, are, weakened])]). relacion([sujeto(['The', ranking, of, calculated]), verbo([binding]), complemento([energies, in, 3, complex, systems, is, well, consistent, with, that, of, experimental, binding, affinities])]). relacion([sujeto(['Fusarium', langsethiae, is, a, fungal, pathogen, of, cereal, crops, that, is, an]), verbo([increasing]), complemento([problem, in, northern, 'Europe,', but, much, of, its, epidemiology, is, poorly, understood])]). relacion([sujeto(['While', our, data]), verbo([suggested]), complemento([that, aphid, transmission, of, the, pathogen, was, not, very, 'efficient,', we, observed, an, increase, in, disease, when, aphids, were, present])]). relacion([sujeto(['After', seedling, 'inoculation,', an]), verbo([increase]), complemento([in, pathogen, 'DNA', accumulation, in, seedling, leaves, was, observed, upon, treatment, with, aphids])]). relacion([sujeto(['langsethiae-inoculated', ears, not, only]), verbo([led]), complemento([to, a, rise, in, the, amount, of, 'F'])]). relacion([sujeto([langsethiae, 'DNA', in, infected, grain, but, also, to, an]), verbo([increase]), complemento([in, the, concentrations, of, 'T-2', and, 'HT-2', 'toxins,', with, more, than, 3, -, fold, higher, toxin, levels, than, diseased, plants, without, aphids])]). relacion([sujeto(['This', work, highlights, that, aphids]), verbo([increase]), complemento([the, susceptibility, of, wheat, host, plants, to, 'F'])]). relacion([sujeto([langsethiae, and, that, aphid, infestation, is, a, risk, factor, for, accumulating]), verbo([increased]), complemento([levels, of, 'T-2', and, 'HT-2', in, wheat, products])]). relacion([sujeto(['Fusarium', langsethiae, is, shown, here, to]), verbo([cause]), complemento([increased, contamination, levels, of, grain, with, toxins, produced, by, fungus, when, aphids, share, the, host, plant])]). relacion([sujeto(['This', effect]), verbo([has]), complemento([also, recently, been, demonstrated, with, 'Fusarium', 'graminearum,', yet, the, two, fungal, species, show, stark, differences, in, their, effect, on, aphid, populations])]). relacion([sujeto(['In', both, 'cases,', aphids, improve, the, ability, of, the, pathogens, to]), verbo([cause]), complemento([and, initiate, 'Fusarium', head, blight, '(', 'FHB)', disease, in, 'wheat,', but, 'F'])]). relacion([sujeto([langsethiae, may, be, able, to]), verbo([act]), complemento([as, a, dispersal, agent])]). relacion([sujeto(['This', work]), verbo([reveals]), complemento([insights, into, the, role, aphids, play, in, promoting, the, successful, colonization, of, this, species, in, wheat, and, the, benefit, of, controlling, aphid, populations, on, crops, that, are, at, high, risk, of, 'FHB'])]). relacion([sujeto(['When', these, processes, are, in, 'competition,', selection, may]), verbo([act]), complemento([to, drive, functional, dimorphism])]). relacion([sujeto(['Investment', in, underground, resources, probably, allows, these, plants, to, manage, the, costs, of, reproduction]), verbo([associated]), complemento([with, increased, dimorphy])]). relacion([sujeto(['Fertile-sterile', dimorphy]), verbo([has]), complemento([evolved, multiple, times, in, ferns, in, spite, of, the, apparent, physiological, costs, associated, with, a, reduction, in, photosynthetically, active, tissues])]). relacion([sujeto(['These', apparent, costs, may, be, offset, by, an]), verbo([increase]), complemento([in, potential, spore, dispersal, distance, 'and/or', increased, spore, production])]). relacion([sujeto(['Defining', the, epitopes, of, 'strain-specific', antibodies, that, overlap]), verbo([conserved]), complemento([sites, of, vulnerability, might, provide, mechanistic, insights, into, how, broadly, neutralizing, antibodies, arise])]). relacion([sujeto(['We', previously, described, an, 'HIV-1', clade, 'C-infected', 'donor,', 'CAP257,', who, developed, broadly, neutralizing, plasma, antibodies]), verbo([targeting]), complemento([an, 'N276', 'glycan-dependent', epitope, in, the, 'CD4', binding, site])]). relacion([sujeto(['The', initial, 'CD4']), verbo([binding]), complemento([site, response, potently, neutralized, the, heterologous, tier, 2, clade, 'B', viral, strain, 'RHPA,', which, was, used, to, design, resurfaced, gp120, antigens, for, 'single-B-cell', sorting])]). relacion([sujeto(['Here', we]), verbo([report]), complemento([the, isolation, and, structural, characterization, of, 'CAP257-RH1,', an, 'N276', 'glycan-dependent', 'CD4', binding, site, antibody, representative, of, the, early, 'CD4', binding, site, plasma, response, in, donor, 'CAP257'])]). relacion([sujeto(['The', cocrystal, structure, of, 'CAP257-RH1']), verbo([bound]), complemento([to, 'RHPA', gp120, revealed, critical, interactions, with, the, 'N276', 'glycan,', loop, 'D,', and, 'V5,', but, not, with, aspartic, acid, 368, ',', similarly, to, 'HJ16', and, 179, 'NC75'])]). relacion([sujeto(['Its', narrow, neutralization, breadth, was, attributed, to, a]), verbo([binding]), complemento([angle, that, was, incompatible, with, glycosylated, 'V5', loops, present, in, almost, all, 'HIV-1', 'strains,', including, the, 'CAP257', 'transmitted/founder', virus])]). relacion([sujeto(['These', 'glycan-free', 'V5', loops, are, unusual, holes, in, the, glycan, shield, that, may]), verbo([have]), complemento([been, necessary, for, initiating, this, 'N276', 'glycan-dependent', 'CD4', binding, site, 'B-cell', lineage])]). relacion([sujeto(['The']), verbo([conserved]), complemento(['CD4', binding, site, on, gp120, is, a, major, target, for, 'HIV-1', vaccine, 'design,', but, key, events, in, the, elicitation, and, maturation, of, different, antibody, lineages, to, this, site, remain, elusive])]). relacion([sujeto(['Studies']), verbo([have]), complemento([shown, that, 'strain-specific', antibodies, can, evolve, into, broadly, neutralizing, antibodies, or, in, some, cases, act, as, helper, lineages])]). relacion([sujeto(['In', this, 'study,', we, isolate, a, narrowly, neutralizing, 'N276', 'glycan-dependent', antibody, and, use, 'X-ray', crystallography, and, viral, deep, sequencing, to, describe, how, gp120, lacking, glycans, in, 'V5', might]), verbo([have]), complemento([elicited, these, early, 'glycan-dependent', 'CD4', binding, site, antibodies])]). relacion([sujeto(['These', data, highlight, how, glycan, holes, can, play, a, role, in, the, elicitation, of, 'B-cell', lineages]), verbo([targeting]), complemento([the, 'CD4', binding, site])]). relacion([sujeto(['As', the, pesticide, exposed, male, workers, were]), verbo([found]), complemento([to, consume, alcohol, and, smoked, 'cigarettes/bidis,', 35, smokers, and, 30, alcoholics, were, also, included, for, comparison])]). relacion([sujeto([1, ')', ',']), verbo([nuclear]), complemento([bud, '(', 4.98, ±, 1.31, ',', p, '≤'])]). relacion([sujeto([1, ')', ',']), verbo([nuclear]), complemento([bud, '(', 4.06, ±, 1.97, ',', p, '≤'])]). relacion([sujeto([1, ')', nuclei, was, higher, in, the, alcoholics, than, control, '(', 'non-alcoholics),', whereas, the, micronuclei, and]), verbo([nuclear]), complemento([bud, were, found, to, be, 'non-significant', compared, with, the, control])]). relacion([sujeto(['Our', analyses, also, revealed, a, higher, proportion, of, the, micronucleus, and, the, cell, death, parameters, in, the, pesticide, exposed, males, than, 'females,', which, indicated, that, 'pesticide,', 'smoking,', and, alcohol, may]), verbo([act]), complemento([synergistically, to, cause, more, damage, to, the, buccal, epithelial, cells])]). relacion([sujeto(['However,', age, and, the, exposure, duration]), verbo([have]), complemento([no, influence, on, the, micronucleus, and, other, cell, death, parameters])]). relacion([sujeto(['Current', evidence]), verbo([suggests]), complemento([that, many, 'GWAS', and, 'IL1', 'SNPs', are, associated, with, periodontal, diseases, but, their, functional, role, remains, ambiguous])]). relacion([sujeto(['Therefore,', it, is, imperative, to, elucidate, the, molecular, pathways, through, which, these, 'SNPs', might]), verbo([act]), complemento([on, the, development, of, the, disease])]). relacion([sujeto(['The', purpose, of, this, review, was, to, highlight, the, regulatory, elements, of, noncoding, regions, of, the, genome, and]), verbo([provide]), complemento([insights, on, the, functional, role, of, 'periodontitis-associated', 'GWAS', and, 'IL1', 'SNPs'])]). relacion([sujeto(['GWAS', and, 'IL1', 'SNPs', overlap, 'DNase', 'I', hypersensitivity, 'sites,', histone, modifications, and, transcription]), verbo([binding]), complemento([sites])]). relacion([sujeto(['SNPs']), verbo([associated]), complemento([with, periodontal, diseases, may, contribute, to, the, development, of, the, disorder, through, their, functional, roles])]). relacion([sujeto(['Challenge', with, 'quartz,', 'silica,', and, rutile, particles]), verbo([induced]), complemento([significant, chemotaxis, of, unexposed, 'NR8383', macrophages])]). relacion([sujeto(['Chemotaxis']), verbo([caused]), complemento([by, quartz, and, silica, was, accompanied, by, an, elevated, transcription, of, 'CCL3,', 'CCL4,', 'CXCL1,', 'CXCL3,', and, 'TNFα'])]). relacion([sujeto(['Barium', sulfate, and, anatase, did, not]), verbo([induce]), complemento([chemotaxis, and, barium, sulfate, as, well, caused, no, elevated, transcription])]). relacion([sujeto(['In', 'conclusion,', 'NR8383', macrophages]), verbo([respond]), complemento([to, the, challenge, with, inflammatory, particles, with, the, release, of, chemotactic, compounds, that, act, on, unexposed, macrophages])]). relacion([sujeto(['Communication']), verbo([has]), complemento([been, suggested, as, a, mechanism, to, stabilize, cooperation])]). relacion([sujeto(['In', 'bacteria,', chemical, 'communication,', termed, quorum, sensing, '(', 'QS),']), verbo([has]), complemento([been, hypothesized, to, fill, this, 'role,', and, extracellular, public, goods, are, often, induced, by, 'QS', at, high, cell, densities])]). relacion([sujeto(['Here', we, 'show,', with, the, bacterium, 'Vibrio', 'harveyi,', that, 'QS']), verbo([provides]), complemento([strong, resistance, against, invasion, of, a, 'QS', defector, strain, by, maximizing, the, cellular, growth, rate, at, low, cell, densities, while, achieving, maximum, productivity, through, protease, upregulation, at, high, cell, densities])]). relacion([sujeto(['In', 'contrast,', 'QS', mutants, that]), verbo([act]), complemento([as, defectors, or, unconditional, cooperators, maximize, either, the, growth, rate, or, the, growth, 'yield,', 'respectively,', and, thus, are, less, fit, than, the, 'wild-type', 'QS', strain])]). relacion([sujeto(['Our', findings]), verbo([provide]), complemento([experimental, evidence, that, regulation, mediated, by, microbial, communication, can, optimize, growth, strategies, and, stabilize, cooperative, phenotypes, by, preventing, defector, 'invasion,', even, under, 'well-mixed', conditions])]). relacion([sujeto(['This', effect, is, due, to, a, combination, of, responsiveness, to, environmental, conditions]), verbo([provided]), complemento([by, 'QS,', lowering, of, competitive, costs, when, 'QS', is, not, 'induced,', and, pleiotropic, constraints, imposed, on, defectors, that, do, not, perform, 'QS'])]). relacion([sujeto(['Thus,', among, 'bacteria,', 'QS']), verbo([has]), complemento([been, proposed, to, be, a, proximate, stabilizing, mechanism, for, cooperative, behaviors])]). relacion([sujeto([harveyi]), verbo([prevents]), complemento([cheating, and, subsequent, invasion, by, nonproducing, defectors, by, maximizing, the, growth, rate, at, low, cell, densities, and, the, growth, yield, at, high, cell, 'densities,', whereas, an, unconditional, cooperator, is, rapidly, driven, to, extinction, by, defectors])]). relacion([sujeto(['Our', findings]), verbo([provide]), complemento([experimental, evidence, that, 'QS', regulation, prevents, the, invasion, of, cooperative, populations, by, 'QS', defectors, even, under, unstructured, 'conditions,', and, they, strongly, support, the, role, of, communication, in, bacteria, as, a, mechanism, that, stabilizes, cooperative, traits])]). relacion([sujeto(['Aspirin']), verbo([has]), complemento([been, used, in, the, treatment, and, chemoprevention, of, many, malignant, cancers])]). relacion([sujeto(['The', mechanism, of, its, 'anti-cancer', activity, mainly]), verbo([involves]), complemento([the, inhibition, of, 'cyclooxygenase-2', '(', 'COX-2)'])]). relacion([sujeto(['We']), verbo([have]), complemento([previously, reported, the, preparation, of, a, novel, aspirin, derivative, that, we, named, 'Ca-Asp,', and, showed, that, it, causes, less, damage, to, gastric, mucosa, of, rat, and, inhibits, the, expression, of, 'COX-2', to, higher, degree, than, 'Asp'])]). relacion([sujeto(['Subsequent', investigation, into, the, possible, underlying, mechanism, showed, that, 'Ca-Asp']), verbo([induced]), complemento([apoptosis, and, caused, cell, cycle, arrest, at, the, 'G1', phase])]). relacion([sujeto(['Ca-Asp', also, 'up-regulated', the, levels, of, 'caspase-3', and, 'p53,', but, down]), verbo([regulated]), complemento([the, level, of, cyclin, 'D1,', 'NF-κB,', 'COX-2', and, 'PGE2'])]). relacion([sujeto(['Taken', 'together,', the, results]), verbo([suggested]), complemento([that, 'Ca-Asp', might, act, as, a, potential, 'anti-cancer', 'drug,', and, that, its, suppression, of, 'PGE2', production, might, constitute, an, important, part, of, its, 'anti-cancer', activity])]). relacion([sujeto(['Contamination', of, aquatic, habitats, with, anthropogenic, nutrients]), verbo([has]), complemento([been, associated, with, an, increase, in, mosquito, larval, populations, but, the, underlying, mechanisms, remain, poorly, understood])]). relacion([sujeto(['The', bacterial, and, fungal, communities, of, water, samples, from, different, fertilizer, treatments, were, also, characterized, by, 'MiSeq', sequencing, of, the, 16, 'S', rRNA, gene, '(', 'bacteria)', and, internal]), verbo([transcribed]), complemento([spacer, 1, '(', 'fungi)', and, their, relationship, with, mosquito, survival, and, development, determined])]). relacion([sujeto(['Microbial', composition, but, not, diversity, was, significantly]), verbo([associated]), complemento([with, mosquito, survival, and, development])]). relacion([sujeto(['These', findings]), verbo([suggest]), complemento([that, anthropogenic, nutrients, can, have, a, profound, impact, on, mosquito, survival, and, development])]). relacion([sujeto(['In', addition, to, any, potential, direct, effects, on, mosquito, 'physiology,', our, results]), verbo([suggest]), complemento([that, fertilizers, can, act, indirectly, by, disrupting, the, microbial, communities, that, provide, a, critical, food, resource, for, mosquito, larvae])]). relacion([sujeto(['Echimidine', is, one, of, the, predominant, 'PAs']), verbo([found]), complemento([in, honeys, produced, in, 'Australia', and, 'New', 'Zealand'])]). relacion([sujeto(['Consumption', of, 'lasiocarpine,', but, not, 'echimidine,']), verbo([decreased]), complemento([bodyweight, gain, in, males, at, '≥', 1.2, &, 'nbsp;mg/kg', 'bw,', and, in, females, at, 2.5, &, 'nbsp;mg/kg', bw])]). relacion([sujeto(['In', 'conclusion,', the, subchronic, 'No', 'Observed', 'Adverse', 'Effect', 'Level', '(', 'NOAEL)', for, echimidine, is, 2.5, &, 'nbsp;mg/kg bw/day,', 'whereas,', on, the, basis, of, a, 'treatment-related']), verbo([decrease]), complemento([in, bodyweight, gain, in, males, at, 1.2, &, 'nbsp;mg/kg', 'bodyweight,', the, 'NOAEL', for, lasiocarpine, is, 0.6, &, 'nbsp;mg/kg bw/day'])]). relacion([sujeto(['On', multivariable, 'analysis,', dosing, was, not]), verbo([associated]), complemento([with, seizures])]). relacion([sujeto(['However']), verbo([increasing]), complemento(['Cmaxss', '(', 'OR', =, 1.1, ',', 95, '%', 'CI', 1.03, ',', 1.17, ')', and, 'AUC24', '(', 'OR', 1.11, ',', 95, '%', 'CI', 1.05, ',', 1.18, ')', were, associated, with, increased, odds, of, seizures])]). relacion([sujeto(['In', this, cohort, of, hospitalized, 'infants,', higher, ampicillin, exposure, was]), verbo([associated]), complemento([with, seizures, as, documented, in, the, 'EHR'])]). relacion([sujeto(['Arsenic', and, polycyclic, aromatic, hydrocarbon, '(', 'PAH)', exposures, affect, many, people, worldwide]), verbo([leading]), complemento([to, cancer, and, other, diseases])]). relacion([sujeto(['Arsenite', '(', 'As(+3))', and, certain, 'PAHs', are, known, to]), verbo([cause]), complemento([genotoxicity])]). relacion([sujeto(['Our', previous, studies, showed, that, environmentally, relevant, concentrations, of, 'As(+3)']), verbo([induce]), complemento([genotoxicity, in, mouse, thymus, cells, through, 'Poly(ADP-ribose)', polymerase, '(', 'PARP)', inhibition])]). relacion([sujeto(['Certain', 'PAHs,', such, as, the, metabolites, of, 'benzo(a)pyrene', '(', 'BaP),', are, known, to]), verbo([cause]), complemento(['DNA', damage, by, forming, 'DNA', adducts])]). relacion([sujeto(['An', interactive]), verbo([increase]), complemento([in, genotoxicity, and, apoptosis, were, observed, following, treatments, with, 5, nM, 'As', '(', +, ')', '(', 3, ')', +, '(', ')', 100, nM, 'BP-diol', and, 50, nM, 'As', '(', +, ')', '(', 3, ')', +, '(', ')', 100, nM, 'BPDE'])]). relacion([sujeto(['We', attribute, the]), verbo([increase]), complemento([in, 'DNA', damage, to, inhibition, of, 'PARP', inhibition, leading, to, decreased, 'DNA', repair])]). relacion([sujeto(['To', further, support, this, 'hypothesis,', we]), verbo([found]), complemento([that, a, 'PARP', 'inhibitor,', 3, ',', 4, -, 'dihydro-5[4-(1-piperindinyl)', 'butoxyl]-1(2H)-isoquinoline', '(', 'DPQ),', also, interacted, with, 'BP-diol', to, produce, an, increase, in, 'DNA', damage])]). relacion([sujeto(['Interestingly,', we, also]), verbo([found]), complemento([that, 'As(+3)', and, 'BP-diol', increased, 'CYP1A1', and, 'CYP1B1', 'expression,', suggesting, that, increased, 'PAH', metabolism, may, also, contribute, to, genotoxicity])]). relacion([sujeto(['In', 'summary,', these, results, show, that, the, suppression, of, 'PARP', activity, and, induction, of, 'CYP1A1/CYP1B1', may]), verbo([act]), complemento([together, to, increase, 'DNA', damage, produced, by, 'As(+3)', and, 'PAHs'])]). relacion([sujeto(['Early', evidence]), verbo([suggests]), complemento([that, removal, of, the, relevant, lymphovascular, package, and, associated, cancer, as, part, of, complete, mesocolic, excision, '(', 'CME),', rather, than, the, entire, right, 'colon,', may, produce, better, outcomes])]). relacion([sujeto(['The', literature, to, date, does, not, reflect, the, precision, of, anatomical, understanding]), verbo([required]), complemento([for, 'CME;', 'hence,', a, new, definition, for, the, right, colic, vessel, is, proposed])]). relacion([sujeto(['The', phase, 'III', trial, proved, that, local, intralesional, injections, with, 'T-Vec', in, advanced, malignant, melanoma, patients, can, not, only]), verbo([suppress]), complemento([the, growth, of, injected, tumors, but, also, act, systemically, and, prolong, overall, survival])]). relacion([sujeto(['This', new, system, by, the, 'Japanese', government, should]), verbo([provide]), complemento(['G47∆', with, priority, reviews, and, a, 'fast-track', drug, approval, by, the, regulatory, authorities])]). relacion([sujeto(['Whereas', numerous, oncolytic, viruses]), verbo([have]), complemento([been, subjected, to, clinical, 'trials,', the, common, feature, that, is, expected, to, play, a, major, role, in, prolonging, the, survival, of, cancer, patients, is, an, induction, of, specific, antitumor, immunity, in, the, course, of, 'tumor-specific', viral, replication])]). relacion([sujeto(['Patients', with, severe, allergic, asthma, above, recommended, dosing, criteria, for, omalizumab]), verbo([have]), complemento([significantly, improved, symptom, 'control,', quality, of, life, and, lung, function, to, a, similar, degree, to, 'within-range', 'participants,', achieved, without, dose, escalation, above, 750, mg])]). relacion([sujeto(['Why', do, one, set, of, cells, die, while, adjacent, cells, remain, 'alive,', if, this, is, the, 'case?', 'There', is, evidence, to]), verbo([suggest]), complemento([that, phytoglobins, '(', 'Pgbs;', previously, termed, 'non-symbiotic', 'hemoglobins)', may, act, as, binary, switches, to, determine, plant, cellular, responses, to, perturbations])]). relacion([sujeto(['There', are, anywhere, from, one, to, five, 'Pgb', genes, in, plants, that, are]), verbo([expressed]), complemento([in, response, to, growth, and, development, and, to, stress])]). relacion([sujeto(['This', review, will, discuss, how, 'Pgb']), verbo([modulates]), complemento([cellular, responses, to, 'auxin,', 'cytokinin,', and, jasmonic, acid, during, growth, and, development, and, in, response, to, stress])]). relacion([sujeto(['Physicians', and, hospital, systems, often]), verbo([have]), complemento([relationships, with, biomedical, manufacturers, to, develop, new, 'ideas,', 'products,', and, further, education])]). relacion([sujeto(['Because', this, relationship, can, influence, medical, research, and, 'practice,']), verbo([reporting]), complemento([disclosures, are, necessary, to, reveal, any, potential, bias, and, inform, consumers])]). relacion([sujeto(['The', 'Sunshine', 'Act', was, created, 'to develop', a, new]), verbo([reporting]), complemento([system, of, these, financial, relationships, called, the, 'Open', 'Payments', database])]). relacion([sujeto(['We', aimed, to, describe, concordance, between, 'physicians\'', financial, disclosures, listed, in, the, abstract, book, from, the, 41, st, annual, scientific, meeting, of, the, 'Society', of, 'Gynecologic', 'Surgeons', to, physician, payments]), verbo([reported]), complemento([to, the, 'Center', for, 'Medicaid', and, 'Medicare', 'Services', 'Open', 'Payments', database, for, the, same, year])]). relacion([sujeto(['A', total, of, 209, of, 335, physicians, '(', 62, '%', ')', had, transactions]), verbo([reported]), complemento([in, the, 'Center', for, 'Medicaid', and, 'Medicare', 'Services,', which, totaled, '$1'])]). relacion([sujeto(['Transactions']), verbo([reported]), complemento([in, the, 'Center', for, 'Medicaid', and, 'Medicare', 'Services', associated, with, a, single, physician, ranged, from, '$11'])]). relacion([sujeto(['Few', studies]), verbo([have]), complemento([assessed, the, dietary, quality, of, children, who, eat, meals, from, home, compared, with, school, meals, according, to, the, 2010, 'Dietary', 'Guidelines', for, 'Americans'])]). relacion([sujeto(['Eating', school, lunch, was]), verbo([associated]), complemento([with, higher, overall, diet, quality, compared, with, obtaining, lunch, from, home])]). relacion([sujeto([',', we]), verbo([found]), complemento([that, human, emotional, tears, act, as, a, social, chemosignal])]). relacion([sujeto(['We']), verbo([find]), complemento([that, 'Gračanin,', who, are, not, a, chemosignaling, 'laboratory,', used, methodology, that, falls, short, of, standards, typically, applied, in, chemosignaling, research])]). relacion([sujeto(['Finally,', we]), verbo([found]), complemento([that, in, reanalysing, their, raw, data, we, could, in, fact, replicate, the, effect, from, 'Gelstein'])]). relacion([sujeto(['We']), verbo([found]), complemento([that, out, of, 192, 'women,', 116, signed, the, 'Health', 'Information', 'Portability', and, 'Accountability', 'Act', form, 'and,', among, 'these,', 97, had, medical, records, that, could, be, verified, '(', 97, /, 116, =, 83.6, '%', ')'])]). relacion([sujeto(['In', spite, of, some, 'limitations,', our, findings, support, the, usage, of, 'self-reported', data, on, mammography, as, a, validated, tool, for, other, researchers, investigating, mammography, screening, among, minority, women, who, continue, to]), verbo([have]), complemento([low, screening, rates])]). relacion([sujeto(['Wide', and, discriminate, use, of, antibiotics]), verbo([has]), complemento([resulted, in, serious, biological, and, ecological, 'concerns,', especially, the, emergence, of, antibiotic, resistance])]). relacion([sujeto(['Probiotics', are, defined, as, live, or, 'dead,', or, even, a, component, of, the, microorganisms, that]), verbo([act]), complemento([under, different, modes, of, action, in, conferring, beneficial, effects, to, the, host, or, to, its, environment])]). relacion([sujeto(['Several', probiotics]), verbo([have]), complemento([been, characterized, and, applied, in, fish, and, a, number, of, them, are, of, host, origin])]). relacion([sujeto(['Unlike', some, disease, control, alternatives, being, adapted, and, proposed, in, aquaculture, where, actions, are, 'unilateral,', the, immense, potential, of, probiotics, lies, on, their, multiple, mechanisms, in]), verbo([conferring]), complemento([benefits, to, the, host, fish, and, the, rearing, environment])]). relacion([sujeto(['This', paper]), verbo([provides]), complemento([an, update, on, the, use, of, probiotics, in, finfish, 'aquaculture,', particularly, focusing, on, their, modes, of, action])]). relacion([sujeto(['This', timely, update, affirms, the, importance, of, probiotics, in, fostering, sustainable, approaches, in, aquaculture, and]), verbo([provides]), complemento([avenues, in, furthering, its, research, and, development])]). relacion([sujeto(['Anesthesiologists', must, master, specific, legal, knowledge, to]), verbo([provide]), complemento([care, to, these, patients])]). relacion([sujeto(['Understanding', how, the, 'Law', and, the, 'Federal', 'Council', of, 'Medicine', treat, this, issue, is, critical, to, know, how, to]), verbo([act]), complemento([in, this, context])]). relacion([sujeto(['The', article, analyzes, the, 'Constitution,', 'Criminal', 'Code,', resolutions, of, the, 'Federal', 'Council', of, 'Medicine', '(', 'FCM),', 'opinions,', and, jurisprudence, to, understand, the, limits, of, the, conflict, between, the, autonomy, of, will, of, 'Jehovah\'s', 'Witnesses', to, refuse, transfusion, and, the, 'physician\'s', duty, to]), verbo([provide]), complemento([the, transfusion])]). relacion([sujeto(['In', the, last, 'decades,', a, number, of, new, antimuscarinic, drugs]), verbo([have]), complemento([been, introduced, for, treatment, of, the, overactive, bladder, '(', 'OAB),', defined, symptomatically, '(', 'OAB', 'syndrome)', or, urodynamically, '(', detrusor, 'overactivity)'])]). relacion([sujeto(['Recently,', three, new, drug, principles]), verbo([have]), complemento([been, approved, for, clinical, 'use,', the, β3, -, adrenoceptor, 'agonist,', 'mirabegron,', the, 'phosphodiesterase-5', 'inhibitor,', tadalafil, and, the, blocker, of, afferent, and, efferent, 'nerves,', botulinum, toxin])]). relacion([sujeto(['OAB', is, a, filling, 'disorder,', and, 'ATP', is]), verbo([involved]), complemento([in, the, generation, of, afferent, impulses])]). relacion([sujeto(['In', animal, 'models,', this, strategy, appears, to, work, very, 'well,', but, whether, it]), verbo([translates]), complemento([effectively, to, man, remains, to, be, established])]). relacion([sujeto(['Evidence']), verbo([suggests]), complemento([that, components, of, the, endocannabinoid, system, are, involved, in, regulation, of, bladder, function])]). relacion([sujeto(['Clinical', studies, of, cannabinoid, extracts, on, 'LUTS', are, scarce, and, essentially, restricted, to, patients, with, 'MS,', and, the, results]), verbo([have]), complemento([so, far, not, been, convincing])]). relacion([sujeto(['Amplification', of, endocannabinoid, activity, by]), verbo([inhibiting]), complemento([their, degradation, via, fatty, acid, amide, hydrolase, inhibitors, may, be, an, attractive, 'approach,', but, no, clinical, experiences, in, 'OAB', have, been, reported])]). relacion([sujeto(['Studies', of, the, lower, urinary, tract]), verbo([have]), complemento([indicated, that, several, transient, receptor, potential, '(', 'TRP)', 'channels,', including, 'TRPV1,', 'TRPV2,', 'TRPV4,', 'TRPM8', and, 'TRPA1,', are, expressed, in, the, bladder, and, may, act, as, sensors, of, stretch, 'and/or', chemical, irritation])]). relacion([sujeto(['Animal', studies]), verbo([have]), complemento([shown, that, inhibition, of, these, pathways, can, be, effective, for, the, reduction, in, bladder, activity])]). relacion([sujeto(['However,', the, roles, of, these, channels, for, normal, function, and, in, pathological, states]), verbo([have]), complemento([not, been, 'established,', and, so, far, adverse, effects, '(', 'hyperthermia)', have, hampered, development, of, antagonists])]). relacion([sujeto(['It', is]), verbo([associated]), complemento([with, elevated, risks, of, 'mortality,', cardiovascular, 'disease,', and, high, costs, for, the, treatment, of, renal, failure, with, dialysis, or, transplantation])]). relacion([sujeto(['MicroRNAs', '(', 'miRNAs)', a, class, of, 'small,', 'non-coding', 'RNAs', that]), verbo([act]), complemento([as, 'post-transcriptional', repressors, are, gaining, momentum, as, biomarkers, in, a, number, of, disease, areas])]). relacion([sujeto(['Finally,', we, highlight, the, pitfalls, and, opportunities, of, miRNAs, and]), verbo([provide]), complemento([a, broad, perspective, for, the, future, clinical, development, of, miRNAs, as, biomarkers, in, 'CKD', beyond, the, current, gold, standards, of, eGFR, and, albuminuria])]). relacion([sujeto(['Traditionally,', the, cost, object, in, health, care]), verbo([has]), complemento([been, either, a, service, line, '(', e])]). relacion([sujeto(['We']), verbo([found]), complemento([that, trusts, had, separate, reporting, systems, for, costs, and, clinical, 'outcomes,', engendering, little, use, for, 'PLICSs', to, link, cost, with, quality])]). relacion([sujeto(['We']), verbo([found]), complemento([that, 'PLICSs', had, created, greater, clinical, engagement, in, resource, management, despite, the, fact, that, the, trust, finance, function, had, actively, communicated, 'PLICSs', as, a, new, costing, tool, and, often, required, its, use, 'in,', for, 'example,', business, cases, for, clinical, investment])]). relacion([sujeto(['Operational', financial, management, at, the, trusts, was, undertaken, through, service, line]), verbo([reporting]), complemento(['(', 'SLR)', and, traditional, directorate, budgets])]). relacion([sujeto(['Financial', pressure, within, the, 'NHS,', along, with, its, current, 'competitive,', 'business-oriented', 'ethos,']), verbo([induces]), complemento([trusts, to, act, in, their, own, interests, rather, than, those, of, the, whole, health, economy])]). relacion([sujeto(['However,', many, policy, commentators]), verbo([suggest]), complemento([that, care, integration, is, needed, to, improve, patient, care, and, reduce, costs])]). relacion([sujeto(['London:', 'The', 'Stationery', 'Office;', 2012, ')']), verbo([requires]), complemento([both, competition, and, the, collaboration, needed, to, achieve, care, 'integration,', the, two, are, not, always, compatible])]). relacion([sujeto(['Results', indicated, that, the, majority, of, respondents]), verbo([have]), complemento([performed, bilingual, language, assessments])]). relacion([sujeto(['The', findings, of, this, study, demonstrated, that, although, 'SLPs']), verbo([have]), complemento([become, more, compliant, to, 'ASHA', and, 'IDEA', 'guidelines,', there, is, room, for, improvement, in, terms, of, adequate, training, in, bilingual, language, assessment])]). relacion([sujeto(['P-Rex', proteins, are, guanine, nucleotide, exchange, factors, '(', 'GEFs)', that]), verbo([act]), complemento([on, the, 'Rho/Rac', family, of, 'GTP', binding, proteins])]). relacion([sujeto(['The', activity, of, 'P-Rex', proteins, is]), verbo([regulated]), complemento([by, several, extracellular, stimuli])]). relacion([sujeto(['In', 'fact,', activation, of, growth, factor, receptors]), verbo([has]), complemento([been, reported, to, activate, a, 'phosphorylation/dephosphorylation', cycle, of, 'P-Rex1'])]). relacion([sujeto(['Such', cycle, includes, dephosphorylation, of, serines, 313, and, 319, which, negatively]), verbo([regulate]), complemento([the, 'GEF', activity, of, 'P-Rex1,', together, with, phosphorylation, of, serines, 605, and, 1169, which, favour, 'P-Rex1', 'GEF', activity])]). relacion([sujeto(['However,', the, kinases, that]), verbo([regulate]), complemento([phosphorylation, at, these, different, regulatory, sites, are, largely, unknown])]). relacion([sujeto(['Here', we]), verbo([have]), complemento([investigated, the, potential, regulatory, action, of, several, kinases, on, the, phosphorylation, of, 'P-Rex1', at, 'S313,', 'S319,', 'S605', and, 'S1169'])]). relacion([sujeto(['We', show, that, activation, of, protein, kinase, 'C', '(', 'PKC)']), verbo([caused]), complemento([phosphorylation, of, 'S313,', 'S319', and, 'S1169'])]). relacion([sujeto(['Activation', of, growth, factor, receptors]), verbo([induced]), complemento([phosphorylation, of, 'S1169', through, a, mechanism, that, was, independent, of, 'PKC,', indicating, that, distinct, kinases, and, mechanisms, control, the, phosphorylation, of, 'P-Rex1', at, different, regulatory, serines])]). relacion([sujeto(['Genetic', and, biochemical, studies, confirmed, that, the, 'PKC', isoform, 'PKCδ', was, able, to, directly]), verbo([phosphorylate]), complemento(['P-Rex1', at, 'S313'])]). relacion([sujeto(['Functional', studies, using, cells, with, very, low, endogenous, 'P-Rex1', 'expression,', transfected, with, wild, type, 'P-Rex1', or, a, mutant, form, in, which, 'S313', was, substituted, by, 'alanine,', indicated, that, phosphorylation, at, that, residue, negatively]), verbo([regulated]), complemento(['P-Rex1', exchange, activity])]). relacion([sujeto(['We']), verbo([suggest]), complemento([that, control, of, 'P-Rex1', activity, depends, on, a, highly, dynamic, interplay, among, distinct, signalling, routes, and, its, multisite, phosphorylation, is, controlled, by, the, action, of, different, kinases])]). relacion([sujeto(['Acinar-to-ductal', metaplasia, '(', 'ADM)', and, pancreatic, intraepithelial, neoplasia, '(', 'PanIN)', are, both, precursor, lesions, that]), verbo([lead]), complemento([to, the, development, of, 'PDAC'])]). relacion([sujeto(['Reg', family, proteins, '(', 'Reg1A,', 1, 'B,', 3, 'A/G,', 4, ')', are, a, group, of, 'calcium-dependent', lectins, that]), verbo([promote]), complemento([islet, growth, in, response, to, inflammation, 'and/or', injuries])]). relacion([sujeto(['We']), verbo([found]), complemento([that, 'Reg1A', and, 'Reg3A/G', were, highly, expressed, in, the, 'ADM', tissues, by, immunohistochemistry])]). relacion([sujeto(['In', the, 3, -, dimensional, culture, of, mouse, acinar, 'cells,', 'Reg3A']), verbo([promoted]), complemento(['ADM', formation, with, concurrent, activation, of, 'mitogen-acitvated', protein, kinase])]). relacion([sujeto(['These', results, were, further, validated, by, the, quantification, of, 'Reg', 1, 'A', and, 1, 'B', mRNA, levels, in, the, microdissected, tissues, '(', 22, -, and, 6, -, fold]), verbo([increases]), complemento([vs])]). relacion([sujeto(['To', address, this, 'problem,', we]), verbo([have]), complemento([attempted, to, design, active, anode, materials, with, anion, charge, carriers, and, recently, observed, the, formation, and, dissolution, of, an, electrochemical, film, by, triflate, anions, '(', 'CF3SO3(-))', at, the, surface, of, magnesium, in, an, ionic, liquid, '(', 'IL)', electrolyte, of, 'Mg(CF3SO3)2,', which, represents, a, rare, anode, material])]). relacion([sujeto(['However,', to, our, 'surprise,', we, discovered, that, some, sodium, ions, are]), verbo([involved]), complemento([in, film, formation])]). relacion([sujeto(['The', sodium, ions, are, believed, to]), verbo([act]), complemento([as, a, 'cross-linking', point, for, the, formation, of, a, film, 'network,', which, resulted, in, fairly, good, reversibility, for, film, formation])]). relacion([sujeto(['The', 'molecular-physiological', mechanisms, underlying, temperature, signaling]), verbo([have]), complemento([not, been, fully, elucidated])]). relacion([sujeto(['Molecular-genetic', studies, demonstrated, that, cold, tolerance, is]), verbo([regulated]), complemento([by, additive, functions, of, three, 'Gα', proteins, in, a, 'temperature-sensing', 'neuron,', 'ASJ,', which, is, also, known, to, be, a, 'light-sensing', neuron])]). relacion([sujeto(['Optical', recording, of, calcium, concentration, in, 'ASJ', upon, 'temperature-changes', demonstrated, that, three, 'Gα', proteins]), verbo([act]), complemento([in, different, aspects, of, temperature, signaling])]). relacion([sujeto(['Calcium', concentration, changes, in, 'ASJ', upon, temperature, change, were, unexpectedly]), verbo([decreased]), complemento([in, a, mutant, defective, in, 'phosphodiesterase,', which, is, well, known, as, a, negative, regulator, of, calcium, increase])]). relacion([sujeto(['Our', previous, study, in, 'Kalabakan,', located, in, 'south-east', coast, of, 'Sabah', showed, a, high, prevalence, of, resistance, to, 'CQ', and, 'SP,']), verbo([suggesting]), complemento([the, use, of, the, treatment, may, no, longer, be, effective, in, the, area])]). relacion([sujeto(['This', study, aimed, to]), verbo([provide]), complemento([a, baseline, data, of, antimalarial, drug, resistant, markers, on, 'P'])]). relacion([sujeto(['Mutations', on, genes]), verbo([associated]), complemento([with, 'CQ', '(', pfcrt, and, 'pfmdr1)', and, 'SP', '(', pfdhps, and, 'pfdhfr)', were, assessed, by, 'PCR', amplification, and, restriction, fragment, length, polymorphism])]). relacion([sujeto(['Mutations', on, the, kelch13, marker, '(', 'K13)']), verbo([associated]), complemento([with, artemisinin, resistance, were, determined, by, 'DNA', sequencing, technique])]). relacion([sujeto(['The', assessment, of, pfmdr1, copy, number, variation]), verbo([associated]), complemento([with, mefloquine, resistant, was, done, by, 'real-time', 'PCR', technique])]). relacion([sujeto(['Combining', the, different, resistant, 'markers,', only, two, isolates, were]), verbo([conferred]), complemento([to, have, 'CQ', and, 'SP', treatment, failure, markers, as, they, contained, mutant, alleles, of, pfcrt, and, pfmdr1, together, with, quintuple, 'pfdhps/pfdhfr', mutation, '(', combination, of, pfdhps, 'A437G+A581G', and, pfdhfr, 'C59R+S108N+I164L)'])]). relacion([sujeto(['This', study]), verbo([has]), complemento([demonstrated, a, low, prevalence, of, 'CQ', and, 'SP', resistance, alleles, in, the, study, area])]). relacion([sujeto(['Continuous', monitoring, of, antimalarial, drug, efficacy, is, warranted, and, the, findings]), verbo([provide]), complemento([information, for, policy, makers, in, ensuring, a, proper, malaria, control])]). relacion([sujeto(['The', 'mitogen-activated', protein, kinase, '(', 'MAPK)', signaling, pathway, is, a, cascade, of, protein, kinases, that]), verbo([act]), complemento([in, a, sequential, and, predominantly, linear, 'fashion,', albeit, displaying, some, cross, talk, with, other, signaling, cascades])]). relacion([sujeto(['Recently,', the, development, of]), verbo([targeted]), complemento([drugs, for, the, treatment, of, 'BRAF-mutant', melanoma, has, led, to, the, widespread, implementation, of, molecular, assays, for, the, detection, of, specific, 'BRAF', mutations])]). relacion([sujeto(['There']), verbo([have]), complemento([been, some, attempts, to, standardize, testing, of, 'BRAF', 'mutations,', but, this, has, not, been, achieved, so, far])]). relacion([sujeto(['Here', we]), verbo([provide]), complemento([an, updated, review, on, the, role, of, the, 'MAPK', signaling, pathway, in, the, pathogenesis, of, cutaneous, 'melanoma,', focusing, on, several, different, 'BRAF', mutations, and, their, diagnostic, and, therapeutic, implications])]). relacion([sujeto(['The', advent, of, click, chemistry]), verbo([has]), complemento([had, a, profound, influence, on, almost, all, branches, of, chemical, science])]). relacion([sujeto(['This', is, particularly, true, of, radiochemistry, and, the, synthesis, of, agents, for, positron, emission, tomography, '(', 'PET),', single, photon, emission, computed, tomography, '(', 'SPECT),', and]), verbo([targeted]), complemento([radiotherapy])]). relacion([sujeto(['The', 'selectivity,', 'ease,', 'rapidity,', and, modularity, of, click, ligations, make, them, nearly, ideally, suited, for, the, construction, of, 'radiotracers,', a, process, that, often]), verbo([involves]), complemento([working, with, biomolecules, in, aqueous, conditions, with, inexorably, decaying, radioisotopes])]). relacion([sujeto(['In', the, following, 'pages,', our, goal, is, to]), verbo([provide]), complemento([a, broad, overview, of, the, first, ten, years, of, research, at, the, intersection, of, click, chemistry, and, radiochemistry])]). relacion([sujeto(['The', discussion, will, focus, on, four, areas, that, we, believe, underscore, the, critical, advantages]), verbo([provided]), complemento([by, click, 'chemistry:', '(', 'i)', the, use, of, prosthetic, groups, for, radiolabeling, 'reactions,', '(', 'ii)', the, creation, of, coordination, scaffolds, for, 'radiometals,', '(', 'iii)', the, 'site-specific', radiolabeling, of, proteins, and, 'peptides,', and, '(', 'iv)', the, development, of, strategies, for, in, vivo, pretargeting])]). relacion([sujeto(['Ultimately,', it, is, our, hope, that, this, review, will, not, only, serve, to, educate, readers, but, will, also]), verbo([act]), complemento([as, a, 'springboard,', inspiring, synthetic, chemists, and, radiochemists, alike, to, harness, click, chemistry, in, even, more, innovative, and, ambitious, ways, as, we, embark, upon, the, second, decade, of, this, fruitful, collaboration])]). relacion([sujeto(['Cytohesin', family, proteins]), verbo([act]), complemento([as, guanine, nucleotide, exchange, factors, '(', 'GEFs)', for, the, 'ADP-ribosylation', factor, family, of, small, 'GTP-binding', proteins])]). relacion([sujeto(['Although', 'ApSec7']), verbo([has]), complemento([a, conserved, 'coiled-coil', '(', 'CC)', 'domain,', its, role, was, not, clear])]). relacion([sujeto(['In', this, 'study,', we]), verbo([found]), complemento([that, the, 'CC', domain, of, 'ApSec7', and, 'ARNO/cytohesin', 2, are, involved, in, homodimer, 'formation,', leading, to, efficient, plasma, membrane, targeting, of, 'ApSec7', and, 'ARNO/cytohesin', 2, in, 'HEK293T', cells])]). relacion([sujeto(['Therefore,', deletion, of, the, 'CC', domain, of, 'ApSec7', and, 'ARNO/cytohesin', 2, may, result, in, a]), verbo([loss]), complemento([of, dimerization, and, reduce, plasma, membrane, localization])]). relacion([sujeto(['In', 'addition,', the, 'CC', domains, of, 'ApSec7', and, 'ARNO/cytohesin', 2]), verbo([have]), complemento([partially, or, fully, 'CRM1-dependent', nuclear, export, 'signals,', respectively])]). relacion([sujeto(['Taken', 'together,', our, results]), verbo([suggest]), complemento([that, the, 'CC', domain, of, cytohesin, family, 'proteins,', including, 'ApSec7', and, 'ARNO/cytohesin', 2, ',', has, dual, roles, in, intracellular, 'targeting:', increased, plasma, membrane, targeting, through, homodimer, formation, and, nuclear, exclusion, through, either, a, 'CRM1-dependent', or, a, 'CRM1-independent', pathway])]). relacion([sujeto(['In', 'particular,', culture, substrates, coated, with, proteins, of, interest, in, defined, 'stripes,', including, cell, adhesion, molecules, and, secreted, 'proteins,']), verbo([have]), complemento([been, successfully, used, to, study, neuronal, 'polarization,', a, process, in, which, the, neuron, establishes, axon, and, dendrite, 'identities,', a, critical, architecture, for, the, 'input/output', functions, of, the, neuron])]). relacion([sujeto(['We']), verbo([have]), complemento([recently, used, this, methodology, to, pattern, the, extracellular, protein, 'Semaphorin', 3, 'A', '(', 'Sema3A),', a, secreted, factor, known, to, control, neuronal, development, in, the, mammalian, embryonic, cortex])]). relacion([sujeto(['We', showed, that, 'stripe-patterned', 'Sema3A']), verbo([regulates]), complemento([axon, and, dendrite, formation, during, the, early, phase, of, neuronal, polarization, in, cultured, rat, hippocampal, neurons])]). relacion([sujeto(['We', note, that, same, methodologies, can, be, applied, to, pattern, other, extracellular, proteins, that]), verbo([regulate]), complemento([neuronal, development, in, the, embryonic, 'brain,', as, nerve, growth, factor, '(', 'NGF),', 'brain-derived', neurotrophic, factor, '(', 'BDNF),', and, 'Netrin-1'])]). relacion([sujeto(['We', describe, modifications, of, these, methodologies, for, stripe, micropatterning, of, 'membrane-permeable', analog, of, the, second, messengers, cyclic, 'AMP', '(', 'cAMP)', and, cyclic, 'GMP', '(', 'cGMP),', intracellular, regulators, of, neuronal, polarization, that, might]), verbo([act]), complemento([downstream, of, 'Sema3A'])]). relacion([sujeto(['Semaphorin', guidance, molecules]), verbo([act]), complemento([through, different, receptor, complexes, to, activate, multiple, signaling, cascades, leading, to, changes, in, axonal, growth, cone, behavior, and, morphology])]). relacion([sujeto(['ZIKV', infection]), verbo([induces]), complemento(['cell-cycle', arrest, and, apoptosis, in, proliferating, neural, progenitors])]). relacion([sujeto(['However,', the, mechanisms]), verbo([leading]), complemento([to, these, phenotypes, are, still, largely, obscure])]). relacion([sujeto(['In', this, 'report,', we, explored, the, possible, similarities, between, transcriptional, responses]), verbo([induced]), complemento([by, 'ZIKV', in, human, neural, progenitors, and, those, elicited, by, three, different, genetic, mutations, leading, to, severe, forms, of, microcephaly, in, mice])]). relacion([sujeto(['We']), verbo([found]), complemento([that, the, strongest, similarity, between, all, these, conditions, is, the, activation, of, common, 'P53', downstream, genes])]). relacion([sujeto(['In', agreement, with, these, 'observations,', we]), verbo([report]), complemento([that, 'ZIKV', infection, increases, total, 'P53', levels, and, nuclear, 'accumulation,', as, well, as, 'P53', 'Ser15', 'phosphorylation,', correlated, with, genotoxic, stress, and, apoptosis, induction])]). relacion([sujeto(['Interestingly,']), verbo([increased]), complemento(['P53', activation, and, apoptosis, are, induced, not, only, in, cells, expressing, high, levels, of, viral, antigens, but, also, in, cells, showing, low, or, undetectable, levels, of, the, same, proteins])]). relacion([sujeto(['Moreover,', we, highlight, a, small, group, of, 'P53', effector, proteins, that, could]), verbo([act]), complemento([as, critical, 'mediators,', not, only, in, 'ZIKV-induced', microcephaly, but, also, in, many, genetic, microcephaly, syndromes])]). relacion([sujeto(['A', new, system, of, slits, called, '`spiderweb', 'slits\'']), verbo([have]), complemento([been, developed, for, 'depth-resolved', powder, or, polycrystalline, 'X-ray', diffraction, measurements])]). relacion([sujeto(['The', slits]), verbo([act]), complemento([on, diffracted, 'X-rays', to, select, a, particular, gauge, volume, of, 'sample,', while, absorbing, diffracted, 'X-rays', from, outside, of, this, volume])]). relacion([sujeto(['Although', the, slit, geometry, is, to, some, extent, similar, to, that, of, previously, developed, conical, slits, or, spiral, 'slits,', this, new, design]), verbo([has]), complemento([advantages, over, the, previous, ones, in, use, for, complex, heterogeneous, materials, and, in, situ, and, operando, diffraction, measurements])]). relacion([sujeto(['Electromyography', signals, from, 10, leg, muscles, were, used, to, calculate, the, cumulative, activity]), verbo([required]), complemento([to, traverse, a, unit, of, distance, '(', 'CMAPD)', for, each, muscle, at, each, speed])]). relacion([sujeto(['In', the, old, group, 'CMAPD', was, correlated, with, 'COT,', presented, higher, and, more, variable, 'values,', and, showed, greater]), verbo([increases]), complemento([around, optimal, speed, for, all, studied, muscles])]). relacion([sujeto(['Greater', energy, cost, of, walking, in, older, individuals, seems, to, be, attributable, to]), verbo([increased]), complemento([energy, cost, of, all, lower, limb, muscles])]). relacion([sujeto(['Understanding', perspectives, of, people, with, mental, illness, on, personal, meanings, of, physical, health, is, essential, to]), verbo([ensuring]), complemento([health, services, are, aligned, with, consumer, 'understandings,', 'needs,', and, values])]). relacion([sujeto(['A', qualitative, exploratory, study, was, undertaken]), verbo([involving]), complemento([focus, groups, with, 31, consumers, in, 'The', 'Australian', 'Capital', 'Territory,', 'Australia'])]). relacion([sujeto(['Issue:', 'Although', predictions, that, the, 'Affordable', 'Care', 'Act', '(', 'ACA)', would]), verbo([lead]), complemento([to, reductions, in, 'employer-sponsored', health, coverage, have, not, been, 'realized,', some, of, the, 'law’s', critics, maintain, the, 'ACA', is, nevertheless, driving, higher, premium, and, deductible, costs, for, businesses, and, their, workers])]). relacion([sujeto(['Key', findings, and, 'conclusions:', 'Compared', to, the, five, years]), verbo([leading]), complemento([up, to, the, 'ACA,', premium, growth, for, single, health, insurance, policies, offered, by, employers, slowed, both, in, the, nation, overall, and, in, 33, states, and, the, 'District', of, 'Columbia'])]). relacion([sujeto(['There']), verbo([has]), complemento([been, a, similar, slowdown, in, growth, in, the, amounts, employees, contribute, to, health, plan, costs])]). relacion([sujeto(['Yet', many, families, feel, pinched, by, their, health, care, 'costs:', despite, a, recent, 'surge,', income, growth]), verbo([has]), complemento([not, kept, pace, in, many, areas, of, the, 'U'])]). relacion([sujeto(['There', is]), verbo([increasing]), complemento([interest, in, identifying, natural, bioactive, compounds, that, can, improve, mitochondrial, functionality, and, regulate, apoptosis])]). relacion([sujeto(['Polyphenols']), verbo([act]), complemento([as, antioxidants, and, have, been, documented, to, protect, the, human, body, from, degenerative, diseases, such, as, cardiovascular, diseases, or, cancer])]). relacion([sujeto(['After', cell, 'culture,', the, tumoral, cells, treated, with, the, polyphenolic, extract, showed]), verbo([enhanced]), complemento([mitochondrial, oxidative, 'function,', which, is, likely, related, to, a, decrease, in, oxidative, stress, and, an, increase, in, mitochondrial, biogenesis])]). relacion([sujeto(['In', our, previous, 'study,', 'NKB/NK3R', system]), verbo([has]), complemento([been, shown, to, act, at, the, pituitary, level, to, 'up-regulate', 'SLα', synthesis, and, secretion, in, grass, carp])]). relacion([sujeto(['However,', whether, 'NK3R', expression, can, serve, as, a, regulatory]), verbo([target]), complemento([at, the, pituitary, level, and, contribute, to, 'NKB', interactions, with, other, 'SLα', regulators, is, still, unclear])]). relacion([sujeto(['In', current, 'study,', using, grass, carp, pituitary, cells, as, a, 'model,', we]), verbo([have]), complemento([a, novel, finding, that, 'co-treatment', of, 'SLα/SLβ', with, carp, 'TAC3', gene, 'products,', could, induce, a, noticeable, enhancement, in, 'SLα', mRNA, expression, and, these, potentiating, effects, occurred, with, a, parallel, rise, in, 'NK3R', transcript, level, after, 'SLα/SLβ', treatment])]). relacion([sujeto(['Interestingly,', the, stimulatory, effects, of, 'SLα/SLβ', on, 'NK3R', gene, expression, could, be, further, potentiated, by, 'co-treatment', with, 'IGF-I/-II', and, simultaneous, exposure, of, carp, pituitary, cells, to, 'SLα/SLβ', and, 'IGF-I/-II', in, the, presence, of, 'TAC3', gene, products, was]), verbo([found]), complemento([to, markedly, elevated, 'SLα', mRNA, expression, '(', 20, fold, 'increase)', and, this, synergistic, stimulation, was, mediated, by, 'cAMP/PKA-,', 'PLC/PKC-', and, 'Ca(2+)', -, dependent, cascades, functionally, coupled, with, 'NK3R', activation])]). relacion([sujeto(['These', findings]), verbo([suggest]), complemento([that, local, release, of, 'SLα', via, functional, interactions, with, 'IGF-I/-II', and, 'TAC3/NK3R', system, may, constitute, a, potent, stimulatory, signal, for, 'SLα', gene, expression, in, the, carp, pituitary, via, 'up-regulation', of, 'NK3R', expression])]). relacion([sujeto(['Thin', magnetic, layers, used, as, &, 'quot;free"', layers, in, 'SHO', are, in, contact, with, heavy, metals, having, large, 'spin-orbital', 'interaction,', 'and,', 'therefore,', could, be, subject, to, the, 'spin-Hall', effect, '(', 'SHE)', and, the, interfacial, 'Dzyaloshinskii-Moriya', interaction, '(', 'i-DMI),', which, may]), verbo([lead]), complemento([to, the, nonreciprocity, of, the, excited, spin, waves, and, other, unusual, effects])]). relacion([sujeto(['Here,', we, analytically, and, micromagnetically, study, magnetization, dynamics, excited, in, an, 'SHO', with, oblique, magnetization, when, the, 'SHE', and, 'i-DMI']), verbo([act]), complemento([simultaneously])]). relacion([sujeto(['There', is, international, interest, 'in,', and, continued, concern, 'about,', the, potential, 'long-term', impact, of, involuntary, admission, to, psychiatric, 'institutions,', and, the, effect, this, coercive, action]), verbo([has]), complemento([on, a, 'person\'s', 'well-being', and, human, rights])]). relacion([sujeto(['Involuntary', detention, in, hospital, remains, a, controversial, process, that]), verbo([involves]), complemento([stakeholders, with, competing, concerns, and, who, often, describe, negative, experiences, of, the, 'process,', which, can, have, 'long-lasting', effects, on, the, therapeutic, relationship, with, service, users])]). relacion([sujeto(['The', aim, of, the, present, study, was, to, explore, the, perspectives, of, key, stakeholders]), verbo([involved]), complemento([in, the, involuntary, admission, and, detention, of, people, under, the, 'Mental', 'Health', 'Act', 2001, in, 'Ireland'])]). relacion([sujeto(['Mental', health, law]), verbo([has]), complemento([traditionally, focussed, on, narrower, areas, of, detention, and, 'treatment,', but, human, rights, law, requires, a, greater, refocussing, on, supporting, service, users, to, ensure, a, truly, voluntary, approach, to, care])]). relacion([sujeto(['We']), verbo([report]), complemento([that, cCF10, induction, is, highly, toxic, to, cells, sustaining, a, deletion, of, 'prgU,', a, small, orf, located, immediately, downstream, of, prgB, on, pCF10])]). relacion([sujeto(['Cells', engineered, to, overproduce, 'PrgB,', even, independently, of, other, 'pCF10-encoded', 'proteins,']), verbo([have]), complemento([severely, compromised, cell, envelopes, and, strong, growth, defects])]). relacion([sujeto(['PrgU']), verbo([has]), complemento([an, 'RNA-binding', 'fold,', and, 'prgB-prgU', gene, pairs, are, widely, distributed, among, 'E'])]). relacion([sujeto(['Together,', our, findings, support, a, model, in, which, 'PrgU', proteins, represent, a, novel, class, of, 'RNA-binding', regulators, that]), verbo([act]), complemento([to, mitigate, toxicity, accompanying, overproduction, of, 'PrgB-like', adhesins, in, 'E'])]). relacion([sujeto(['Polycystic', ovary, syndrome, '(', 'PCOS)', was]), verbo([associated]), complemento([with, a, number, of, polymorphisms, of, genes, involved, in, insulin, signaling])]). relacion([sujeto(['So', 'far,', they]), verbo([have]), complemento([been, studied, separately])]). relacion([sujeto(['Publications', were, identified, through]), verbo([targeted]), complemento([literature, searches, in, 'Ovid', 'MEDLINE,', 'PsycINFO,', 'Web', of, 'Science,', 'CINAHL,', and, 'ProQuest', 'Dissertations', &, 'amp;', 'Theses', through, 'March', of, 2015])]). relacion([sujeto(['In', both, 'cases,', the, negative, relationship, implied, that, greater, burnout, among, healthcare, providers, was]), verbo([associated]), complemento([with, 'poorer-quality', healthcare, and, reduced, safety, for, patients])]). relacion([sujeto(['Moderator', analyses]), verbo([suggest]), complemento([contextual, factors, to, consider, for, future, study])]). relacion([sujeto(['Effective', immune, responses]), verbo([require]), complemento([the, precise, regulation, of, dynamic, interactions, between, hematopoietic, and, 'non-hematopoietic', cells])]). relacion([sujeto(['The', 'Rho', subfamily, of, 'GTPases,', which, includes, 'RhoA,', is, rapidly]), verbo([activated]), complemento([downstream, of, a, diverse, array, of, biochemical, and, biomechanical, 'signals,', and, is, emerging, as, an, important, mediator, of, this, 'cross-talk'])]). relacion([sujeto(['The', 'ROCKs', are, two, 'serine-threonine', kinases, that, can]), verbo([act]), complemento([as, global, coordinators, of, a, 'tissue\'s', response, to, stress, and, injury, because, of, their, ability, to, regulate, a, wide, range, of, biological, processes])]). relacion([sujeto(['Although', the, 'RhoA-ROCK', pathway]), verbo([has]), complemento([been, extensively, investigated, in, the, 'non-hematopoietic', 'compartment,', its, role, in, the, immune, system, is, just, now, becoming, appreciated])]). relacion([sujeto(['In', this, 'commentary,', we]), verbo([provide]), complemento([a, brief, overview, of, recent, findings, that, highlight, the, contribution, of, this, pathway, to, lymphocyte, development, and, 'activation,', and, the, impact, that, dysregulation, in, the, activation, of, 'RhoA', 'and/or', the, 'ROCKs', may, exert, on, a, growing, list, of, autoimmune, and, lymphoproliferative, disorders])]). relacion([sujeto(['Several', studies]), verbo([have]), complemento([reported, 'age-associated', changes, in, 'DNA', methylation, in, the, first, few, years, of, life, and, in, adult, 'populations,', but, the, extent, of, such, changes, during, childhood, is, less, well, studied])]). relacion([sujeto(['The', goals, of, this, study, were, to, investigate, to, what, degree, 'intra-individual', changes, in, 'DNA', methylation, are]), verbo([associated]), complemento([with, aging, during, childhood, and, dissect, the, methylation, changes, directly, associated, with, aging, from, the, effect, mediated, through, variation, in, 'cell-type', composition, '(', 'CTC)'])]). relacion([sujeto(['Analyses', separating, the, effect]), verbo([mediated]), complemento([by, 'CTC', variability, across, age, identified, 26, 'CpGs', located, in, 12, genes, that, associated, directly, with, age])]). relacion([sujeto(['Hence,', the, 'CTC', changes, across, age, appear, to]), verbo([act]), complemento([as, a, mediator, of, the, observed, 'DNA', methylation, associated, with, age])]). relacion([sujeto(['Further,', comparisons, of, the, mean, 'DNA', methylation, differences, between, the, time, points]), verbo([reveal]), complemento([greater, differences, between, 2, to, 10, &, 'nbsp;years', and, 10, to, 16, &, 'nbsp;years,', suggesting, that, the, identified, 'age-associated', 'DNA', methylation, patterns, manifests, in, early, childhood])]). relacion([sujeto(['This', study]), verbo([reveals]), complemento([insights, into, the, epigenetic, dynamics, associated, with, aging, early, in, life])]). relacion([sujeto(['Such', information, could, ultimately]), verbo([provide]), complemento([clues, and, point, towards, molecular, pathways, that, are, susceptible, to, 'aging-related', 'disease-associated', epigenetic, dysregulation])]). relacion([sujeto(['To', examine, the, expression, of, 'ALDOB', in, gastric, cancer, '(', 'GC)', tissue, and, to]), verbo([reveal]), complemento([its, potential, clinicopathological, and, prognostic, significance])]). relacion([sujeto(['We', screened, for, genes, that, were, differentially]), verbo([expressed]), complemento([between, 'GC', and, nontumor, tissues, using, a, 'microarray,', specifically, the, 'Affymetrix', 'U133', 'Plus', 2.0, 'Array', platform])]). relacion([sujeto(['Both', 'qRT-PCR', and, 'IHC', validated, the]), verbo([decrease]), complemento([of, 'ALDOB', in, 'GC', tissue])]). relacion([sujeto(['Moreover,', we]), verbo([found]), complemento([that, the, expression, of, 'ALDOB', was, significantly, related, to, 'tumor-invasion', 'depth,', 'lymph-node', 'metastasis,', distant, 'metastasis,', and, 'TNM', stage])]). relacion([sujeto(['The', expression, of, 'ALDOB', in, 'GC', tissue, was, significantly, related, to, the, clinicopathological, features, and, prognosis, of, the, 'disease,', thus]), verbo([suggesting]), complemento([that, 'ALDOB', could, act, as, a, novel, molecular, marker, for, 'GC'])]). relacion([sujeto(['Polymerase', activity, is, responsible, for, viral, 'RNA', synthesis, by, a, de, novo, initiation, mechanism, and, represents, an, attractive]), verbo([target]), complemento([for, antiviral, therapy])]). relacion([sujeto(['The', incidence, of, 'DENV']), verbo([has]), complemento([grown, rapidly, and, it, is, now, estimated, that, half, of, the, human, population, is, at, risk, of, becoming, infected, with, this, virus])]). relacion([sujeto(['The', present, in, silico, study, aimed, at]), verbo([finding]), complemento([new, inhibitors, of, the, 'NS5', 'RNA-dependent', 'RNA', polymerase, of, the, four, serotypes, of, 'DENV'])]). relacion([sujeto(['We', used, a, chemical, library, comprising, 372, ',', 792, nonnucleotide, compounds, '(', around, 325, ',', 319, natural, 'compounds)', to, perform, molecular, docking, experiments, against, a]), verbo([binding]), complemento([site, of, the, 'RNA', template, tunnel, of, the, virus, polymerase])]). relacion([sujeto(['Finally,', after, the, screening, process, was, 'completed,', we, identified, 39, compounds, as]), verbo([lead]), complemento(['DENV', polymerase, inhibitor, candidates])]). relacion([sujeto(['Potentially,', these, compounds, could]), verbo([act]), complemento([as, efficient, 'DENV', polymerase, inhibitors, in, vitro, and, in, vivo])]). relacion([sujeto(['From', within, seminal, 'plasma,', proteins, perform, a, wide, variety, of, distinct, functions, that]), verbo([regulate]), complemento([major, reproductive, events, such, as, fertilization])]). relacion([sujeto(['The', ability, of, such, proteins, to]), verbo([bind]), complemento([and, interact, with, different, antagonistic, ions, and, biomolecules, such, as, 'polysaccharides,', 'lipids,', and, other, proteins, present, in, the, male, and, female, reproductive, tract, define, these, capabilities])]). relacion([sujeto(['Over', the, last, two, 'decades,', extensive, work]), verbo([has]), complemento([been, undertaken, in, an, attempt, to, define, the, role, of, seminal, plasma, 'proteins,', of, 'which,', 'Gelatin', binding, proteins, '(', 'GBPs)', represent, a, large, family])]). relacion([sujeto(['GBPs', comprise, of, known, group, of, 'Bovine', seminal, plasma, '(', 'BSP)', protein, 'family,', matrix, metallo, proteinases, '(', 'MMP', 2, and, 'MMP', 9, ')', and, 'fibronectin,', which]), verbo([have]), complemento([been, widely, studied])]). relacion([sujeto(['The', presence, of, a, type, 'II', repeat, is, a, characteristic, feature, of, 'GBPs,', which, is, similar, in, structure, to, the, fibronectin, type, 'II', domain, '(', 'fn2),', which]), verbo([has]), complemento([ability, to, bind, multiple, ligands, including, 'gelatin,', 'glycosaminoglycans,', choline, 'phospholipids,', and, lipoproteins])]). relacion([sujeto(['Two', fn2, domains, are, present, within, the, 'BSP', protein, 'family,', 'while,', three, fn2, domains, are]), verbo([found]), complemento([in, gelatinases, '(', 'MMP-2', and, 'MMP9),', and, 'ELSPBP1', '(', 'Epididymosomes', 'Transfer', 'Epididymal', 'Sperm', 'Binding', 'Protein', 1, ')', contains, four, long, fn2, domains])]). relacion([sujeto(['For', the, most, part, 'BSP', proteins, are, exclusively]), verbo([expressed]), complemento([in, seminal, vesicles, although, 'mBSPH1,', mBSPH2, and, hBSPH1, are, all, expressed, in, the, epididymis])]). relacion([sujeto(['The', expression, of, gelatinases]), verbo([has]), complemento([been, demonstrated, in, several, organs, and, tissues, such, as, the, 'prostate,', 'testis,', 'epididymis,', 'ovary,', human, 'placenta,', cervix, and, endometrial, wall])]). relacion([sujeto(['This', review, intends, to, bring, current, updates, on, the, role, of, 'GBPs', in, reproductive, physiology, to, 'light,', which, may]), verbo([act]), complemento([as, basis, for, future, studies, on, 'GBPs'])]). relacion([sujeto(['Given', microRNAs]), verbo([act]), complemento([to, destabilize, and, degrade, their, target, 'mRNA,', mRNAs, that, inversely, correlated, with, let7i, were, identified])]). relacion([sujeto(['To', demonstrate, let7i, posttranscriptional, regulation, of]), verbo([target]), complemento(['genes,', a, 3, '\'', untranslated, region, luciferase, assay, was, performed])]). relacion([sujeto(['Let7i', was]), verbo([decreased]), complemento([in, patients, with, acute, ischemic, stroke, '(', fold, change, -, 1.7, ',', p, &, 'lt;', 1.0e-5, ')'])]). relacion([sujeto(['The']), verbo([decrease]), complemento([in, let7i, was, associated, with, increased, expression, of, several, of, its, mRNA, 'targets,', including, 'CD86,', 'CXCL8,', and, 'HMGB1'])]). relacion([sujeto(['In', vitro, studies, confirm, let7i, posttranscriptional, regulation, of]), verbo([target]), complemento([genes, 'CD86,', 'CXCL8,', and, 'HMGB1'])]). relacion([sujeto(['Functional', analysis, predicted, let7i]), verbo([regulates]), complemento([pathways, involved, in, leukocyte, 'activation,', 'recruitment,', and, proliferation, including, canonical, pathways, of, 'CD86', signaling, in, 'T', helper, 'cells,', 'HMGB1', 'signaling,', and, 'CXCL8', signaling])]). relacion([sujeto(['Let7i', is]), verbo([decreased]), complemento([in, circulating, leukocytes, of, patients, with, acute, ischemic, stroke])]). relacion([sujeto(['Mechanisms', by, which, let7i]), verbo([regulates]), complemento([inflammatory, response, post, stroke, include, targeting, 'CD86,', 'CXCL8,', and, 'HMGB1'])]). relacion([sujeto(['Sphingolipids', '(', 'SLs)', are, ubiquitous, elements, in, eukaryotic, membranes, and, are, also]), verbo([found]), complemento([in, some, bacterial, and, viral, species])]). relacion([sujeto(['As', well, as, playing, an, integral, structural, 'role,', 'SLs', also]), verbo([act]), complemento([as, potent, signalling, molecules, involved, in, numerous, cellular, pathways, and, have, been, linked, to, many, human, diseases])]). relacion([sujeto(['Furthermore,', we, determined, the, 'x-ray', crystal, structure, of, the, 'PLP-bound', form, of, 'S1PL2021', at, 2.1, 'Å', resolution]), verbo([revealed]), complemento([the, enzyme, displays, a, conserved, structural, fold, and, active, site, architecture, comparable, with, known, 'S1PLs'])]). relacion([sujeto(['The', combined, data]), verbo([suggest]), complemento([that, 'B'])]). relacion([sujeto([pseudomallei]), verbo([has]), complemento([the, potential, to, degrade, host, 'SLs', in, a, 'S1PL-dependent', manner])]). relacion([sujeto(['Affordable', 'Care', 'Act', provisions, implemented, in, 2014, could]), verbo([have]), complemento([influenced, 'employers\'', decisions, to, offer, health, insurance])]). relacion([sujeto(['Using', data, for, 2014, from, the, 'Medical', 'Expenditure', 'Panel', 'Survey-Insurance', 'Component,', we]), verbo([found]), complemento([little, change, in, 'employer-sponsored', health, insurance, 'offerings:', 'More', than, 95, &, 'nbsp;percent', of, employers, either, continued, offering, coverage, or, continued, not, offering, it, between, 2013, and, 2014])]). relacion([sujeto(['To', describe, a, dynamic, 'three-dimensional', '(', 3, 'D)', computed, tomography, '(', 'CT)', technique, for, the, upper, airway, and, compare, the]), verbo([required]), complemento([radiation, dose, to, that, used, for, common, clinical, studies, of, a, similar, anatomical, 'area,', such, as, for, subjects, undergoing, routine, clinical, facial, 'CT'])]). relacion([sujeto(['Lung', cancer, is, a]), verbo([leading]), complemento([cause, of, 'cancer-related', deaths, worldwide])]). relacion([sujeto(['Lung', cancer, risk, 'factors,', including, smoking, and, exposure, to, environmental, 'carcinogens,']), verbo([have]), complemento([been, linked, to, chronic, inflammation])]). relacion([sujeto(['Within', this, 'T', cell, subset, are, immunosuppressive, regulatory, 'T', '(', 'Treg)', cells, and, 'pro-inflammatory', 'T', helper, 17, '(', 'Th17)', cells, that]), verbo([act]), complemento([in, a, fine, balance, to, regulate, appropriate, adaptive, immune, responses])]). relacion([sujeto(['In', the, context, of, lung, 'cancer,', evidence]), verbo([suggests]), complemento([that, 'Tregs', promote, metastasis, and, metastatic, tumor, foci, development])]). relacion([sujeto(['Additionally,', 'Th17', cells]), verbo([have]), complemento([been, shown, to, be, an, integral, component, of, the, inflammatory, milieu, in, the, tumor, 'microenvironment,', and, potentially, involved, in, promoting, distinct, lung, tumor, phenotypes])]). relacion([sujeto(['Studies']), verbo([have]), complemento([shown, that, the, composition, of, 'Tregs', and, 'Th17', cells, are, altered, in, the, tumor, 'microenvironment,', and, that, these, two, 'CD4(+)', 'T', cell, subsets, play, active, roles, in, promoting, lung, cancer, progression, and, metastasis])]). relacion([sujeto(['In', drug, 'development,', in, vitro, human, model, systems, are, absolutely, essential, prior, to, the, clinical, 'trials,', considering, the]), verbo([increasing]), complemento([number, of, chemical, compounds, in, need, of, 'testing,', 'and,', keeping, in, mind, that, animals, cannot, predict, all, the, adverse, human, health, effects, and, 'reactions,', due, to, the, 'species-specific', differences, in, metabolic, pathways])]). relacion([sujeto(['In', vitro, liver, model, systems, by, using, highly, differentiated, human, cells, could]), verbo([have]), complemento([a, great, impact, in, preclinical, trials])]). relacion([sujeto(['Membranes']), verbo([act]), complemento([as, an, extracellular, matrix, for, the, adhesion, of, hepatocytes, and, compartmentalise, them, in, a, 'well-defined', physical, and, chemical, microenvironment, with, high, selectivity])]). relacion([sujeto(['Advanced', 3, -, 'D', tissue, cultures, are, furthermore, achieved, by, using, membrane, bioreactors, '(', 'MBR),', which]), verbo([ensure]), complemento([the, continuous, perfusion, of, cells, protecting, them, from, shear, stress])]). relacion([sujeto(['These', devices, that]), verbo([promote]), complemento([the, 'long-term', maintenance, and, differentiation, of, primary, human, hepatocytes, with, preserved, liver, specific, functions, can, be, employed, in, drug, testing, for, prolonged, exposure, to, chemical, compounds, and, for, assessing, 'repeated-dose', toxicity])]). relacion([sujeto(['The', use, of, primary, human, hepatocytes, in, membrane, bioreactors, is, the, only, system]), verbo([providing]), complemento([a, faster, and, more, 'cost-effective', method, of, analysis, for, the, prediction, of, in, vitro, human, drug, metabolism, and, enzyme, induction, alternative, 'and/or', complementary, to, animal, experimentation])]). relacion([sujeto(['These', receptors, sense, a, variety, of, signaling, 'molecules,']), verbo([activate]), complemento([multiple, intracellular, signal, 'pathways,', and, act, as, the, targets, of, over, 40, '%', of, marketed, drugs])]). relacion([sujeto(['Recent', progress, on, 'GPCR', structural, studies]), verbo([provides]), complemento([invaluable, insights, into, the, 'structure-function', relationship, of, the, 'GPCR', 'superfamily,', deepening, our, understanding, about, the, molecular, mechanisms, of, 'GPCR', signal, transduction])]). relacion([sujeto(['A gastric', subtype, was, recently, described, that, showed, no, association, with, 'high-risk', human, papillomavirus, '(', 'HPV)', 'infections,']), verbo([has]), complemento(['a poor', 'prognosis,', is, mainly, diagnosed, in, women, of, 'Asian', origin, and, can, occur, in, patients, with, 'Peutz-Jeghers', syndrome])]). relacion([sujeto(['Although', no, clear, grading, system]), verbo([has]), complemento([been, recommended, in, the, 'WHO', 'classification,', it, is, likely, that, grading, of, adenocarcinomas, of, the, uterine, cervix, will, partly, be, based, on, the, different, patterns, of, invasion])]). relacion([sujeto(['In', the, near, future, a, maximum, tumor, size, of, 2, &, 'nbsp;cm', could]), verbo([act]), complemento([as, a, discriminator, for, planning, of, less, radical, surgery])]). relacion([sujeto(['Parameters', of, the, histopathological]), verbo([report]), complemento([that, are, relevant, for, the, prognostic, assessment, as, well, as, the, choice, of, adjuvant, treatment, and, function, as, quality, indicators, during, certification, are, described])]). relacion([sujeto(['Adult', patients, in, the, waiting, rooms, of, 4, 'FQHCs', who, 'self-reported', risky, drug, use, on, the, screening, instrument, 'World', 'Health', 'Organization\'s', 'Alcohol,', 'Smoking', and, 'Substance', 'Involvement', 'Screening', 'Test', '(', score, 4, -, 26, ')', ',', who]), verbo([participated]), complemento([in, the, &, 'quot;Quit', 'Using', 'Drugs', 'Intervention', 'Trial,"', submitted, urine, samples, for, drug, testing])]). relacion([sujeto(['Of', the, 192, eligible, 'participants,', 189, '(', 96, '%', ')']), verbo([provided]), complemento([urine, samples])]). relacion([sujeto(['Thirty', patients, '(', 22, '%', ')', 'under-reported', drug, use, and, 105, '(', 78, '%', ')']), verbo([reported]), complemento([drug, use, accurately])]). relacion([sujeto(['Logistic', regression, revealed, that, 'under-reporting', of, any, drug, was]), verbo([associated]), complemento([with, history, of, incarceration, and, older, age, '(', odds, ratios, 2.6, and, 3.3, ',', 'respectively;', 'P', &, 'lt;', 0.05, ')'])]). relacion([sujeto(['Because', effort, can, serve, as, an, index, of, goal, 'importance,', greater, effort, in, performing, immoral]), verbo([acts]), complemento([would, lead, to, more, negative, 'judgments,', whereas, greater, effort, in, performing, moral, acts, would, lead, to, more, positive, judgments])]). relacion([sujeto(['In', support, of, these, 'ideas,', we]), verbo([found]), complemento([that, perceived, effort, intensified, judgments, of, both, immoral, '(', 'Studies', 1, -, 2, ')', and, moral, '(', 'Studies', 2, -, 7, ')', agents])]). relacion([sujeto(['Furthermore,', the, effect, of, effort, on, judgment, was]), verbo([mediated]), complemento([by, perceived, goal, importance, '(', 'Studies', 4, -, 6, ')', ',', even, when, controlling, for, perceived, intentions, '(', 'Studies', 5, -, 6, ')'])]). relacion([sujeto(['(', 'PsycINFO', 'Database', 'Record', 'Rhipicephalus', '(', 'Boophilus)', microplus, ticks, are, obligatory, hematophagous, ectoparasites, of, cattle, and]), verbo([act]), complemento([as, vectors, for, 'disease-causing', microorganisms])]). relacion([sujeto(['Conventional', tick, control, is, based, on, the, use, of, chemical, 'acaricides;', 'however,', their, uncontrolled, use]), verbo([has]), complemento([increased, tSresistant, tick, 'populations,', as, well, as, food, and, environmental, contamination])]). relacion([sujeto(['Alternative', immunological, tick, control]), verbo([has]), complemento([shown, to, be, partially, effective])]). relacion([sujeto([1, 'D', and, 2, 'D', 'SDS-PAGE-Western', blot, assays, with, sera, from, immunized, cattle]), verbo([recognized]), complemento([several, ovarian, proteins])]). relacion([sujeto([&, 'nbsp;microplus']), verbo([has]), complemento([several, 'Vitellogenin', 'members,', which, are, proteolytically, processed, to, generate, multiple, polypeptide, fragments])]). relacion([sujeto(['This', apparent, complexity, of, vitellogenic, tick, molecular]), verbo([targets]), complemento([gives, the, opportunity, to, explore, their, potential, usefulness, as, vaccine, candidates, 'but,', at, the, same, 'time,', imposes, a, challenge, on, the, selection, of, the, appropriate, set, of, antigens])]). relacion([sujeto(['Pluripotent', mouse, embryonic, stem, cells]), verbo([maintain]), complemento([their, identity, throughout, virtually, infinite, cell, divisions])]). relacion([sujeto(['This', 'phenomenon,', referred, to, as, 'self-renewal,', depends, on, a, network, of, 'sequence-specific', transcription, factors, '(', 'TFs)', and]), verbo([requires]), complemento([daughter, cells, to, accurately, reproduce, the, gene, expression, pattern, of, the, mother])]). relacion([sujeto(['However,', dramatic, chromosomal, changes, take, place, in, 'mitosis,', generally]), verbo([leading]), complemento([to, the, eviction, of, 'TFs', from, chromatin])]). relacion([sujeto(['Here,', we]), verbo([report]), complemento([that, 'Esrrb,', a, major, pluripotency, 'TF,', remains, bound, to, key, regulatory, regions, during, mitosis])]). relacion([sujeto(['We', show, that, mitotic, 'Esrrb']), verbo([binding]), complemento([is, highly, 'dynamic,', driven, by, specific, recognition, of, its, 'DNA-binding', motif, and, is, associated, with, early, transcriptional, activation, of, target, genes, after, completion, of, mitosis])]). relacion([sujeto(['These', results, indicate, that, 'Esrrb', may]), verbo([act]), complemento([as, a, mitotic, bookmarking, 'factor,', opening, another, perspective, to, molecularly, understand, the, role, of, 'sequence-specific', 'TFs', in, the, epigenetic, control, of, 'self-renewal,', pluripotency, and, genome, reprogramming])]). relacion([sujeto(['First,', are, mate, guarding, 'and/or', frequent, copulation, positively, correlated, with, a, 'male\'s', share, of, paternity, at, his, 'nest?', 'We']), verbo([find]), complemento([a, significant, positive, correlation, between, both, presumed, paternity, protection, behaviors, and, paternity, share])]). relacion([sujeto(['For', 'example,', more, attractive, males, might]), verbo([have]), complemento([less, need, to, protect, their, paternity])]). relacion([sujeto(['Second,', do, males, with, higher, indices, of, 'so-called', male, &, 'quot;quality"', '(', phenotypic, 'measures,', usually, subjectively, defined, by, researchers, as, predictors, of, male, 'attractiveness)', exhibit, lower, levels, of, paternity, protection, 'behavior?', 'We']), verbo([find]), complemento([a, negative, correlation, between, male, quality, and, paternity, protection])]). relacion([sujeto(['This']), verbo([finding]), complemento([might, partly, explain, the, weak, relationship, between, paternity, protection, and, 'paternity,', although, we, discuss, 'other,', nonmutually, exclusive, possibilities])]). relacion([sujeto(['Biologists']), verbo([have]), complemento([taken, the, concept, of, organism, largely, for, granted])]). relacion([sujeto(['However,', advances, in, the, study, of, 'chimerism,', 'symbiosis,', 'bacterial-eukaryote', 'associations,', and, microbial, behavior]), verbo([have]), complemento([prompted, a, redefinition, of, organisms, as, biological, entities, exhibiting, low, conflict, and, high, cooperation, among, their, parts])]). relacion([sujeto(['Recognizing', that, organismality, can, be, context, 'dependent,', we, advocate, elucidating, the, ecological, contexts, under, which, entities, do, or, do, not]), verbo([act]), complemento([as, organisms])]). relacion([sujeto(['Here', we, develop, a, &, 'quot;contextual', 'organismality"', framework, and]), verbo([provide]), complemento([examples, of, 'entities,', such, as, honey, bee, 'colonies,', 'tumors,', and, bacterial, 'swarms,', that, can, act, as, organisms, under, specific, life, 'history,', 'resource,', or, other, ecological, circumstances])]). relacion([sujeto(['We']), verbo([suggest]), complemento([that, context, dependence, may, be, a, stepping, stone, to, the, development, of, increased, organismal, 'unification,', as, the, most, integrated, biological, entities, generally, show, little, context, dependence])]). relacion([sujeto(['Through', the, same, experimental, 'system,', we]), verbo([find]), complemento([that, 'Escherichia', coli, 'NarK', and, 'NarU', can, complement, deletions, in, both, narK, and, nasA, in, 'P'])]). relacion([sujeto(['denitrificans,']), verbo([suggesting]), complemento(['that,', while, these, proteins, are, most, likely, 'nitrate/nitrite', 'antiporters,', they, can, also, act, in, the, net, uptake, of, nitrate])]). relacion([sujeto(['Finally,', we, argue, that, primary, sequence, analysis, and, structural, modelling, do, not, readily, explain, why, 'NasA,', 'NarK1', and, 'NarK2,', as, well, as, other, transporters, from, this, protein, 'family,']), verbo([have]), complemento([such, different, 'functions,', ranging, from, net, nitrate, uptake, to, 'nitrate/nitrite', exchange])]). relacion([sujeto(['This', species, is, hypothesized, to]), verbo([have]), complemento([spread, to, the, 'Americas', 1.5, &, 'nbsp;million', years, 'ago,', founding, a, population, that, is, at, 'present,', a, distinct, 'species,', 'Helicoverpa', zea])]). relacion([sujeto([&, 'nbsp;armigera', was, confirmed, to]), verbo([have]), complemento(['re-entered', 'South', 'America', via, 'Brazil', and, subsequently, spread])]). relacion([sujeto(['Primarily,', we]), verbo([find]), complemento([that, 'Brazilian', 'H'])]). relacion([sujeto([&, 'nbsp;zea,', and, are, able, to]), verbo([provide]), complemento([genomic, support, for, the, presence, of, the, 'H'])]). relacion([sujeto(['Polycomb', group, proteins, form, two, main, 'complexes,', 'PRC2', and, 'PRC1,', which, generally, coregulate, their]), verbo([target]), complemento([genes])]). relacion([sujeto(['Here', we, show, that, 'PRC1', components]), verbo([act]), complemento([as, neoplastic, tumor, suppressors, independently, of, 'PRC2', function])]). relacion([sujeto(['These', genes, massively, outnumber, canonical]), verbo([targets]), complemento([and, are, mainly, involved, in, the, regulation, of, cell, 'proliferation,', signaling, and, polarity])]). relacion([sujeto(['Alterations', in, 'PRC1', components, specifically, deregulate, this, set, of, 'genes,', whereas, canonical]), verbo([targets]), complemento([are, derepressed, in, both, 'PRC1', and, 'PRC2', mutants])]). relacion([sujeto(['In', human, embryonic, stem, 'cells,', 'PRC1', components, colocalize, with, 'H3K27me3', as, in, 'Drosophila', 'embryos,', whereas, in, differentiated, cell, types, they, are, selectively]), verbo([recruited]), complemento([to, a, large, set, of, proliferation, and, 'signaling-associated', genes, that, lack, 'H3K27me3,', suggesting, that, the, redeployment, of, 'PRC1', components, during, development, is, evolutionarily, conserved])]). relacion([sujeto(['Plasmin', activity]), verbo([leads]), complemento([to, tissue, 'degradation,', direct, and, through, activation, of, metalloproteinases])]). relacion([sujeto(['These', will, coat, the, root, canal, walls, and]), verbo([act]), complemento([as, conditioning, films, that, allow, bacterial, biofilms, to, grow, and, be, a, potential, source, of, hematogenously, spreading, bacteria])]). relacion([sujeto(['Four-species', biofilms, cultured, for, 96, &, 'nbsp;h', showed, that, streptococci]), verbo([increased]), complemento([their, proportion, with, time])]). relacion([sujeto(['The', specificity, of, the]), verbo([binding]), complemento([to, plasminogen, was, verified, by, blocking, 'lysine-binding', sites, with, 'epsilon-aminocaproic', acid])]). relacion([sujeto(['This']), verbo([binding]), complemento([may, contribute, to, their, spread, locally, as, well, as, to, distant, organs, or, tissues])]). relacion([sujeto(['This', method, is, shown, to]), verbo([have]), complemento([80, '%', power, to, detect, changes, of, 14, '%', ',', 27, '%', ',', 26, '%', and, 19, '%', between, two, serial, measurements, in, a, given, individual])]). relacion([sujeto(['Percentage', distribution, of, office, visits, by, patient, age, was]), verbo([found]), complemento([to, be, 20, '%', &, 'lt;15', years, 'old,', 7, '%', 15, to, 24, years, 'old,', 21, '%', 25, to, 44, years, 'old,', 32, '%', 45, to, 64, years, 'old,', 11, '%', 65, to, 74, years, 'old,', and, 10, '%', '≥75', years, old])]). relacion([sujeto(['This', 30, '%', to, 50, '%', underestimation, of, the, otolaryngology, workforce]), verbo([has]), complemento([an, impact, on, future, predictions, and, resource, utilization, analysis])]). relacion([sujeto(['Even', when, this, correction, is, 'considered,', the, available, trained, otolaryngologists]), verbo([required]), complemento([to, serve, the, otolaryngologic, health, care, needs, of, the, 'US', population, are, still, insufficient, and, understaffed])]). relacion([sujeto(['The', aim, of, this, study, was, to]), verbo([provide]), complemento([evidence, that, actions, performed, by, an, individual, influence, the, sensorimotor, memory, processing, 'and,', in, 'particular,', the, integration, process])]). relacion([sujeto(['The', 1, st, experiment, consisted, of, a, 'short-term', priming, paradigm, based, on, 2, 'phases:', a, learning, 'phase,', consisting, of, the, association, between, a, shape, and, a, 'sound,', and, a, test, 'phase,', examining, the, priming, effect, of, the, shape, seen, in, the, learning, phase, on, the, processing, of]), verbo([target]), complemento([tones])]). relacion([sujeto(['In', 'Experiment', 1, ',', we, showed, that, '(', 'a)', the, prime]), verbo([associated]), complemento([with, the, sound, in, the, learning, phase, had, an, effect, on, target, processing, and, '(', 'b)', the, component, reactivated, by, the, prime, was, perceptual, in, nature, '(', i])]). relacion([sujeto(['Experiment', 3, showed, that, the, integration, process]), verbo([required]), complemento([the, individual, to, act, while, learning, the, association, between, the, shape, and, the, 'sound;', otherwise, no, integration, effect, was, observed])]). relacion([sujeto(['We', showed, that, 'α1-AT', 'Pittsburgh']), verbo([inhibits]), complemento([tissue, plasminogen, activator, and, plasmin])]). relacion([sujeto([α1, -, 'Antitrypsin', '(', α1, -, 'AT)', 'Pittsburgh']), verbo([has]), complemento([a, 'Met358', to, 'Arg', substitution, at, the, reactive, 'Met-Ser', site, of, α1, -, 'AT,', which, enables, the, protein, to, act, as, a, potent, thrombin, inhibitor])]). relacion([sujeto(['Four', patients, with, α1, -, 'AT', 'Pittsburgh']), verbo([have]), complemento([been, described, to, date])]). relacion([sujeto(['This', observation]), verbo([suggests]), complemento([that, the, in, vivo, consequences, of, the, mutation, may, contribute, to, the, maintenance, of, normal, hemostatic, balance])]). relacion([sujeto(['Our', results, indicate, that, the, 'patient\'s', plasma, and, purified, α1, -, 'AT', 'Pittsburgh']), verbo([have]), complemento([strong, potential, to, inhibit, 'tissue-type', plasminogen, activator, and, plasmin])]). relacion([sujeto(['Scaffolds']), verbo([provide]), complemento([a, physical, support, for, osteoblasts, and, act, as, the, medium, to, transfer, mechanical, stimuli, to, cells])]). relacion([sujeto(['To', verify, our, hypothesis, that, the, surface, chemistry, of, scaffolds]), verbo([regulates]), complemento([the, perception, of, cells, to, mechanical, 'stimuli,', the, sensitivity, and, tolerability, of, osteoblasts, to, fluid, shear, stress, '(', 'FSS)', of, various, magnitudes, '(', 5, ',', 12, ',', 20, 'dynes/cm(2)', ')', were, investigated, on, various, surface, chemistries, '(', -, 'OH,', -, 'CH3', ',', -, 'NH2', ')', ',', and, their, 'follow-up', effects, on, cell, proliferation, and, differentiation, were, examined, as, well])]). relacion([sujeto(['The', sensitivity, was, characterized, by, the]), verbo([release]), complemento([of, adenosine, triphosphate, '(', 'ATP),', nitric, oxide, '(', 'NO)', and, prostaglandin, 'E2', '(', 'PGE2', ')', while, the, tolerability, was, by, cellular, membrane, integrity])]). relacion([sujeto(['Observations', on, the, focal, adhesion, 'formation,', 'F-actin', organization, and, cellular, orientation, before, and, after, 'FSS', exposure]), verbo([suggest]), complemento([that, the, potential, mechanism, lies, in, the, differential, control, of, 'F-actin', organization, and, focal, adhesion, formation, by, surface, 'chemistry,', which, further, divergently, mediates, the, sensitivity, and, tolerability, of, 'ROBs', to, 'FSS', and, the, 'follow-up', cell, proliferation, and, differentiation])]). relacion([sujeto(['These', findings, are, essentially, valuable, for, 'design/selection', of, desirable, surface, chemistry, to, orchestrate, with, 'FSS', 'stimuli,']), verbo([inducing]), complemento([appropriate, cell, responses, and, promoting, bone, formation])]). relacion([sujeto(['This', can, manifest, as, differences, in, 'patients\'', experiences, and, response, to, 'pain,', which]), verbo([require]), complemento([an, individualized, approach, to, pain, management])]). relacion([sujeto(['Prophylaxis', with, factor, replacement, reduces, the, likelihood, of, bleeds, and, 'bleed-related', 'pain,', whereas, 'on-demand', therapy]), verbo([ensures]), complemento([rapid, bleed, resolution, and, pain, relief])]). relacion([sujeto(['Nevertheless,', a, combination, of, medications, that]), verbo([act]), complemento([at, different, points, in, the, pain, pathway, may, be, beneficial])]). relacion([sujeto(['In', the, longer, 'term,']), verbo([increasing]), complemento([use, of, prophylaxis, or, performing, surgery, may, be, necessary, to, reduce, the, burden, of, pain, caused, by, the, degenerative, effects, of, repeated, bleeds])]). relacion([sujeto(['Two', experiments, assessed, whether, flow, selectively]), verbo([interacted]), complemento([with, compensatory, 'and/or', guidance, levels, of, steering, 'control,', under, either, unconstrained, gaze, or, constrained, gaze, conditions])]). relacion([sujeto(['Optic', flow, speed, was, manipulated, independent, of, the, veridical, 'road-edges', so, that, use, of, flow, would]), verbo([lead]), complemento([to, predictable, understeering, or, oversteering])]). relacion([sujeto(['Steering', was]), verbo([found]), complemento([to, systematically, vary, according, to, flow, 'speed,', but, crucially, the, 'Flow-Induced', 'Steering', 'Bias', '(', 'FISB)', magnitude, depended, on, which, 'road-edge', components, were, visible])]). relacion([sujeto(['The', presence, of, a, guidance, signal]), verbo([increased]), complemento([the, influence, of, 'flow,', with, the, largest, 'FISB', in, '\'', 'Far\'', and, '\'', 'Complete\'', road, 'conditions,', whereas, the, smallest, 'FISB', was, observed, when, only, '\'', 'Near\'', 'road-edges', were, visible])]). relacion([sujeto(['Overall', the, experiments, demonstrate, that, optic, flow, can]), verbo([act]), complemento([indirectly, upon, steering, control, by, modulating, the, guidance, signal, provided, by, a, demarcated, path])]). relacion([sujeto(['Changes', from, the, initial, visit, to, the, first, 'follow-up', visit, at, '∼', 3, months, '(', corresponding, to, a, comparison, of, rivaroxaban, vs, prior, 'VKA)', for, 'ACTS', burden, and, benefit, scores, were, calculated, using, and]), verbo([reported]), complemento([as, least, squared, mean, differences, '(', 'LSMDs)', with, 95, '%', confidence, intervals, '(', 'CIs)'])]). relacion([sujeto(['Fifty-four', percent, and, 48, '%', of, patients]), verbo([reported]), complemento([experiencing, at, least, a, minimally, important, clinical, difference, in, burden, and, benefit, 'scores,', respectively])]). relacion([sujeto(['Caspase-8', is, a, key, initiator, of, apoptotic, cell, death, where, it, functions, as, the, apical, protease, in, death, 'receptor-mediated', apoptosis]), verbo([triggered]), complemento([via, the, 'death-inducing', signalling, complex, '(', 'DISC)'])]). relacion([sujeto(['However,', the, observation, that, 'caspase-8', is, upregulated, in, many, common, tumour, types]), verbo([led]), complemento([to, the, discovery, of, alternative, 'non-apoptotic,', 'pro-survival', 'functions,', many, of, which, are, contingent, on, phosphorylation, of, a, tyrosine, residue, '(', 'Y380)', found, in, the, linker, region, between, the, two, catalytic, domains, of, the, enzyme])]). relacion([sujeto(['Furthermore,', 'Src-mediated', 'Y380', phosphorylation]), verbo([leads]), complemento([to, increased, resistance, to, 'CD95-induced', 'apoptosis;', 'however,', the, mechanism, underlying, this, impaired, response, to, extrinsic, apoptotic, stimuli, has, not, been, identified])]). relacion([sujeto(['Consequently,', we]), verbo([have]), complemento([employed, a, number, of, model, systems, to, further, dissect, this, protective, mechanism])]). relacion([sujeto(['First,', using, an, in, vitro, 'DISC', model, together, with, recombinant, 'procaspase-8', 'variants,', we, show, that, 'Y380', phosphorylation]), verbo([inhibits]), complemento(['procaspase-8', activation, at, the, 'CD95', 'DISC,', thereby, preventing, downstream, activation, of, the, caspase, cascade])]). relacion([sujeto(['Second,', we, validated, this]), verbo([finding]), complemento([in, a, cellular, context, using, transfected, neuroblastoma, cell, lines, deficient, in, 'caspase-8'])]). relacion([sujeto(['Reconstitution', of, these, lines, with, 'phosphomimetic-caspase-8', results, in]), verbo([increased]), complemento([resistance, to, 'CD95-mediated', apoptosis, and, enhanced, cell, migration])]). relacion([sujeto(['When', the, in, vitro, 'DISC', is, assembled, in, the, presence, of, cell, 'lysate,', 'caspase-8', 'Y380', phosphorylation, attenuates, 'DISC', activity, by]), verbo([inhibiting]), complemento(['procaspase-8', autoproteolytic, activity, but, not, recruitment, or, homodimerization, of, 'caspase-8', within, the, complex])]). relacion([sujeto(['Once', incorporated, into, the, 'DISC,']), verbo([phosphorylated]), complemento(['caspase-8', is, unable, to, be, released, from, the, 'complex;', this, inhibits, further, cycling, and, release, of, active, catalytic, subunits, into, the, 'cytoplasm,', thus, resulting, in, increased, apoptotic, resistance])]). relacion([sujeto(['Taken', 'together,', our, novel, findings, expand, our, understanding, of, the, key, mechanisms, underlying, the, 'anti-apoptotic', functions, of, 'caspase-8', which, may]), verbo([act]), complemento([as, a, critical, block, to, existing, antitumour, therapies])]). relacion([sujeto(['New', active, ingredients, from, this, group, of, fungicides]), verbo([have]), complemento([been, introduced, recently, and, are, widely, used])]). relacion([sujeto(['Because', the, fungicides]), verbo([act]), complemento([at, a, single, enzyme, 'site,', resistance, development, in, 'Z'])]). relacion([sujeto(['This', is, the, first]), verbo([report]), complemento([showing, that, the, 'SdhC-H152R', mutation, detected, in, laboratory, mutagenesis, studies, also, exists, in, the, field])]). relacion([sujeto(['Intentional', deception, is, a, common]), verbo([act]), complemento([that, often, has, detrimental, 'social,', 'legal,', and, clinical, implications])]). relacion([sujeto(['In', the, last, 'decade,', brain, activation, patterns]), verbo([associated]), complemento([with, deception, have, been, mapped, with, functional, magnetic, resonance, imaging, '(', 'fMRI),', significantly, expanding, our, theoretical, understanding, of, the, phenomenon])]). relacion([sujeto(['Using', a, logistic, 'regression,', we]), verbo([found]), complemento([that, fMRI, experts, were, 24, '%', more, likely, '(', relative, risk, =, 1.24, ',', 'P', &, 'lt;'])]). relacion([sujeto(['Impulsivity,', the, tendency, to]), verbo([act]), complemento([quickly, without, adequate, planning, or, concern, for, 'consequences,', is, a, commonly, cited, risk, factor, for, suicidal, thoughts, and, behaviour])]). relacion([sujeto(['Physical', inactivity]), verbo([has]), complemento([been, 'recognized,', by, the, 'World', 'Health', 'Organization', as, the, fourth, cause, of, death, '(', 5.5, &, 'nbsp;%', 'worldwide)'])]). relacion([sujeto(['On', the, 'contrary,', physical, activity, '(', 'PA)']), verbo([has]), complemento([been, associated, with, improved, quality, of, life, and, decreased, risk, of, several, diseases, '(', i])]). relacion([sujeto(['Several', 'molecules,', secreted, by, muscle, '(', 'myokines)', and, adipose, tissues, '(', 'adipokines)', in, response, to, 'exercise,', are]), verbo([involved]), complemento([in, the, fine, regulation, of, bone, metabolism, in, response, to, the, energy, availability])]). relacion([sujeto(['Furthermore,', bone]), verbo([regulates]), complemento([energy, metabolism, by, communicating, its, energetic, needs, thanks, to, osteocalcin, which, acts, on, pancreatic, 'β-cells', and, adipocytes])]). relacion([sujeto([',', 'irisin,', 'IL-6,', 'LIF,', 'IGF-I)', 'which,', 'instead,']), verbo([act]), complemento([as, 'inflammatory/pro-resorptive', mediators, when, chronically, 'elevated;', on, the, other, 'hand,', the, reduction, in, the, circulating, levels, of, adipokines, '(', i])]). relacion([sujeto(['Two', types, of, stack, models, were, 'investigated:', a, 'four-layer', stack, with, cells, seeded, at, the, bottom, surface, of, the, 'first/top', layer, and, the, top, surface, of, the, 'fourth/bottom', 'layer,', so, that, the, two, middle, layers, were, not, seeded, with, cells, with, the, aim, to]), verbo([act]), complemento([as, continuing, conduits, of, culture, medium, and, nutrients, supply, to, the, adjacent, 'cell-populated', 'zones;', a, 'three-layer', stack, with, cells, seeded, at, the, bottom, surface, of, each, layer])]). relacion([sujeto(['Hence,', the, regularly, seeded, 'three-layer', stack]), verbo([maintained]), complemento(['cell-free', porous, zones, in, all, layers, through, which, the, culture, medium, could, continuously, 'perfuse,', while, good, fusion, was, achieved, at, the, interface, of, all, layers, via, the, 'cross-migrating', cells, with, a, preference, to, downwards, vertical, migration, attributed, to, gravity])]). relacion([sujeto(['Dynamic', cell, culture, conditions]), verbo([enhanced]), complemento([overall, cell, growth, by, about, 6, '%', for, the, regularly, seeded, 'three-layer', stack])]). relacion([sujeto(['Although', modes, of, action, '(', 'MOAs)', play, a, key, role, in, the, understanding, of, the, toxic, mechanism, of, 'chemicals,', the, 'MOAs']), verbo([have]), complemento([not, been, investigated, for, antibiotics, to, green, algae])]). relacion([sujeto(['They']), verbo([act]), complemento([as, electrophilic, mechanism, of, action, to, 'P'])]). relacion([sujeto(['Although', numerous, 'GNATs']), verbo([have]), complemento([been, identified, thus, 'far,', many, remain, structurally, and, functionally, uncharacterized])]). relacion([sujeto(['Our', structures, of, 'SACOL1063', show, substantial, flexibility, of, a, loop, that, is, likely, responsible, for, substrate, recognition, and]), verbo([binding]), complemento([compared, to, structures, of, other, homologs])]). relacion([sujeto(['In', the, 'CoA', complex, 'structure,', we]), verbo([found]), complemento([two, 'CoA', molecules, bound, in, both, the, canonical, 'AcCoA/CoA-binding', site, and, the, 'acceptor-substrate-binding', site])]). relacion([sujeto(['Our', work, also]), verbo([provides]), complemento([initial, clues, regarding, the, substrate, specificity, of, these, two, 'enzymes;', 'however,', their, native, 'function(s)', remain, unknown])]). relacion([sujeto(['We']), verbo([found]), complemento([both, proteins, act, as, 'N-', rather, than, 'O-acetyltransferases', and, preferentially, acetylate, 'l-threonine'])]). relacion([sujeto(['The', combination, of, structural, and, kinetic, analyses, of, these, two, previously, uncharacterized, 'GNATs']), verbo([provides]), complemento([fundamental, knowledge, and, a, framework, on, which, future, studies, can, be, built, to, elucidate, their, native, functions])]). relacion([sujeto(['The', conclusion, is, that, there, is, a, fundamental, need, to]), verbo([act]), complemento([in, relation, to, the, real, needs, of, this, population, and, consolidate, proposals, for, health, 'promotion,', health, protection, and, health, rehabilitation, for, them])]). relacion([sujeto(['This', new, understanding]), verbo([has]), complemento([its, origins, in, the, 2006, 'WHO', 'International', 'Classification', of, 'Functioning,', 'Disability,', and, 'Health', -, 'ICF,', the, 2001, 'UN', 'Convention', on, the, 'Rights', of, 'Persons', with, 'Disabilities,', and, more, 'recently,', the, 'July', 2015, 'Brazilian', 'Inclusion', of, 'People', with, 'Disabilities', 'Act', '(', 'IPDA),', also, known, as, the, 'Statute', on, 'Persons', with, 'Disabilities'])]). relacion([sujeto(['This', is, mainly, due, to, the, challenges, of]), verbo([recognizing]), complemento([the, barriers, and, environmental, factors, that, hamper, the, full, participation, in, society, of, people, with, disabilities])]). relacion([sujeto(['We', conduct, experiments, in, three, different, countries, '(', 'Sweden,', 'Austria,', and, the, 'United', 'States)']), verbo([involving]), complemento([over, 1, ',', 400, subjects])]). relacion([sujeto(['All', subjects]), verbo([responded]), complemento([to, four, trolley, type, dilemmas, and, four, dictator, games, involving, different, charitable, causes])]). relacion([sujeto(['Overall', we]), verbo([find]), complemento([converging, evidence, that, intuitive, states, do, not, influence, moral, decisions])]). relacion([sujeto(['Thus', we]), verbo([find]), complemento([no, supporting, evidence, for, the, claim, that, intuitive, moral, judgments, and, dictator, game, giving, differ, from, more, reflectively, taken, decisions])]). relacion([sujeto(['Across', all, samples, and, decision, tasks, men, were, more, likely, to, make, utilitarian, moral, judgments, and]), verbo([act]), complemento([selfishly, compared, to, 'women,', providing, further, evidence, that, there, are, robust, gender, differences, in, moral, 'decision-making'])]). relacion([sujeto(['A', high, dose, range, of, 'SF,', 50.8, -, 62.2, mg, 'L(-1)', over, 48, 'h,', representing, a, c, '(', 'concentration)', x, t, '(', 'time)', products, of, 2438, -, 2985, gh, 'm(-3)', was]), verbo([required]), complemento([for, complete, control, of, eggs, of, 'T'])]). relacion([sujeto([dominca]), verbo([required]), complemento([only, 630, gh, 'm(-3)', for, 48, h, '(', 13.13, mg, 'L(-1)', ')'])]). relacion([sujeto(['Our', research, concludes, that, phosphine, resistance, does, not]), verbo([confer]), complemento([cross, resistance, to, 'SF', in, grain, insect, pests, irrespective, of, the, variation, in, levels, of, tolerance, to, 'SF', itself, or, resistance, to, phosphine, in, their, egg, and, adult, stages])]). relacion([sujeto(['While', our, study, confirms, that, 'SF']), verbo([has]), complemento([potentials, as, a, &, 'quot;phosphine', resistance, 'breaker",', the, observed, higher, tolerance, in, eggs, stresses, the, importance, of, developing, 'SF', fumigation, protocols, with, longer, exposure, periods])]). relacion([sujeto(['In', 1990, ',', the, 'US', 'Congress', amended, the, 'Clean', 'Air', 'Act', '(', 'CAA)', to, reduce, 'regional-scale', ecosystem, degradation, from, 'SO', x, and, 'NO', x, emissions, which]), verbo([have]), complemento([been, responsible, for, acid, deposition, in, regions, such, as, the, 'Adirondack', 'Mountains', of, 'New', 'York', 'State'])]). relacion([sujeto(['A', statistical, analysis, of, 'SO4,', 'pH,', 'Al,', and, 'DOC', data, collected, during, this, project, demonstrates, positive, change, in, response, to]), verbo([decreased]), complemento([deposition])]). relacion([sujeto(['The', changes, in, water, chemistry, also]), verbo([have]), complemento([lowered, the, risk, of, 'Al', toxicity, to, brook, trout, '(', 'Salvelinus', fontinalis, '[', 'Mitchill]),', which, allowed, the, 're-introduction', of, this, species, to, 'Brooktrout', 'Lake', from, which, it, had, been, extirpated])]). relacion([sujeto([fontinalis, also, is, cyclic, and]), verbo([provides]), complemento([rationale, for, the, difficulties, inherent, in, 're-establishing', resident, populations, in, impacted, aquatic, environments])]). relacion([sujeto(['To']), verbo([find]), complemento([potential, molecules, to, inhibit, 'AMPARs,', 'high-throughput', screening, was, performed, in, a, library, of, tetrapeptides, in, silico])]). relacion([sujeto(['Computational', results]), verbo([suggest]), complemento([that, some, tetrapeptides, bind, stably, to, the, 'AMPAR'])]). relacion([sujeto(['Accordingly,', natural, 'EGAR', was, hypothesized, to]), verbo([have]), complemento([anticonvulsant, 'activity,', and, in, vitro, experiments, showed, that, 'EGAR', selectively, inhibited, 'AMPAR-mediated', synaptic, transmission, without, affecting, the, electrophysiological, properties, of, hippocampal, pyramidal, neurons])]). relacion([sujeto(['In', 'conclusion,', the, promising, experimental, results]), verbo([suggest]), complemento([that, 'EGAR', inhibitor, against, 'AMPARs', may, be, a, target, for, antiepilepsy, pharmaceuticals])]). relacion([sujeto(['Here', we]), verbo([provide]), complemento([a, possibility, in, which, a, natural, and, edible, 'tetrapeptide,', 'EGAR,', can, act, as, an, antiepileptic, agent])]). relacion([sujeto(['We']), verbo([have]), complemento([combined, computation, with, in, vitro, experiments, to, show, how, 'EGAR', modulates, epilepsy])]). relacion([sujeto(['We', also, used, an, animal, model, of, epilepsy, to, prove, that, 'EGAR', can]), verbo([inhibit]), complemento([seizures, in, vivo])]). relacion([sujeto(['This', study]), verbo([suggests]), complemento(['EGAR', as, a, potential, pharmaceutical, for, the, treatment, of, epilepsy])]). relacion([sujeto(['It', is, now, widely, established, that, health, care, organizations, are, well, advised, not, only, to, identify, and]), verbo([act]), complemento([upon, the, concerns, of, all, patient, groups, but, also, to, encourage, and, enable, them, to, voice, their, concerns, in, the, first, place])]). relacion([sujeto(['That', 'said,', research]), verbo([has]), complemento([begun, to, reveal, that, patients, differ, substantially, in, their, readiness, to, 'complain,', with, many, deciding, to, remain, silent, even, after, experiencing, severe, adverse, events])]). relacion([sujeto(['Little', research]), verbo([has]), complemento([explored, whether, patients, at, the, margins, '(', e])]). relacion([sujeto(['We', examined, the, extent, to, which, 'patients\'', social, '(', being, elderly, or, poorly, 'educated),', physical, '(', having, a, permanent, impairment, such, as, 'deafness,', 'blindness,', or, a, chronic, physical, 'condition),', and, mental, marginality, '(', having, a, mental, illness, or, learning, 'disability)', is]), verbo([associated]), complemento([with, their, intention, and, perceived, ability, to, complain])]). relacion([sujeto(['Of', 'these,', only, 10.41, '%', indicated, that, hospital, staff]), verbo([provided]), complemento([them, with, all, the, information, they, needed, to, complain])]). relacion([sujeto(['An', additional, 14.7, '%']), verbo([reported]), complemento([to, have, received, at, least, some, of, the, information, needed, for, this, purpose])]). relacion([sujeto(['Patients', at, the, 'margins,', especially, elderly, patients, and, those, with, a, severe, vision, 'impairment,', will, often, remain, silent, and]), verbo([require]), complemento([special, 'attention,', if, health, care, organizations, are, to, listen, 'to-and', learn, 'from-the', voices, of, all, patients])]). relacion([sujeto(['Mechanical', force, and, 'Wnt', signaling]), verbo([activate]), complemento(['β-catenin-mediated', transcription, to, promote, proliferation, and, tissue, expansion])]). relacion([sujeto(['However,', it, is, unknown, whether, mechanical, force, and, 'Wnt', signaling]), verbo([act]), complemento([independently, or, synergize, to, activate, 'β-catenin', signaling, and, cell, division])]). relacion([sujeto(['We', show, that, mechanical, strain]), verbo([induced]), complemento(['Src-dependent', phosphorylation, of, 'Y654', 'β-catenin', and, increased, 'β-catenin-mediated', transcription, in, mammalian, 'MDCK', epithelial, cells])]). relacion([sujeto(['Activating', 'β-catenin', through, 'Casein', 'Kinase', 'I', inhibition, or, 'Wnt3A', addition]), verbo([increased]), complemento(['β-catenin-mediated', transcription, and, 'strain-induced', accumulation, of, cells, in, 'S/G2'])]). relacion([sujeto(['Significantly,', only, the, combination, of, mechanical, strain, and, 'Wnt/β-catenin', activation]), verbo([triggered]), complemento([cells, in, 'S/G2', to, divide])]). relacion([sujeto(['These', results, indicate, that, 'strain-induced', 'Src', phosphorylation, of, 'β-catenin', and, 'Wnt-dependent', 'β-catenin', stabilization, synergize, to]), verbo([increase]), complemento(['β-catenin-mediated', transcription, to, levels, required, for, mitosis])]). relacion([sujeto(['Interventions', to]), verbo([increase]), complemento([cooking, skills, '(', 'CS)', and, food, skills, '(', 'FS)', as, a, route, to, improving, overall, diet, are, popular, within, public, health])]). relacion([sujeto(['Greater', 'CS', and, 'FS', abilities, may, not]), verbo([lead]), complemento([directly, to, healthier, dietary, choices, given, the, myriad, of, other, factors, 'implicated;', 'however,', 'CS', appear, to, have, differential, influences, on, aspects, of, the, 'diet,', most, notably, in, relation, to, lowering, saturated, fat, intake])]). relacion([sujeto(['Findings']), verbo([suggest]), complemento([that, 'CS', and, 'FS', should, not, be, singular, targets, of, interventions, designed, to, improve, 'diet;', but, targeting, specific, 'sub-groups', of, the, population, e])]). relacion([sujeto(['The', effect, of, this, intervention, component, is, seldom]), verbo([reported]), complemento([and, the, evidence, is, inconsistent])]). relacion([sujeto(['We', conducted, a, systematic, process, evaluation, of, the, parental, component, and, examined, whether, the, leveal, of, parental, involvement, in, a, large, 'multi-component', 'intervention:', the, 'Boost', study, was]), verbo([associated]), complemento([with, 'adolescents\'', fruit, and, vegetable, '(', 'FV)', intake, at, 'follow-up'])]). relacion([sujeto(['The', 'Boost', study, was]), verbo([targeting]), complemento(['FV', intake, among, 1, ',', 175, 'Danish', 7, '(', 'th)', graders, '(', '≈13-', 'year-olds)', in, the, school, year, 2010, /, 11])]). relacion([sujeto(['High,', medium, and, low, parental, involvement, was]), verbo([found]), complemento([among, 30.5, &, 'nbsp;%,', 29.6, &, 'nbsp;%', and, 39.4, &, 'nbsp;%', of, the, students, respectively])]). relacion([sujeto(['More', men, agreed, that, the, parental, newsletters]), verbo([provided]), complemento([new, information])]). relacion([sujeto(['However,', several, studies]), verbo([have]), complemento([concluded, that, 'Health', 'Councils', are, not, very, influential, on, healthcare, policy])]). relacion([sujeto(['This', study, probes, this, issue, further, by]), verbo([providing]), complemento([a, descriptive, account, of, some, of, the, challenges, civil, society, face, within, 'Brazil\'s', 'Health', 'Councils'])]). relacion([sujeto(['There', is, a]), verbo([reported]), complemento([lack, of, support, and, recognition, from, the, relevant, government, that, negatively, affects, the, degree, to, which, 'Health', 'Council', deliberations, are, implemented])]). relacion([sujeto(['Lastly,', strong, individual, interests, among, 'Health', 'Council', members, tend, to, influence, how, members]), verbo([participate]), complemento([in, 'Health', 'Council', discussions])]). relacion([sujeto(['Brazil\'s', 'Health', 'Councils', fall, short, in]), verbo([providing]), complemento([an, effective, forum, through, which, civil, society, can, actively, participate, in, health, policy, and, resource, allocation, 'decision-making', processes])]). relacion([sujeto(['Restrictive', membership, 'guidelines,', a, lack, of, autonomy, from, the, 'government,', vulnerability, to, government, 'manipulation,', a, lack, of, support, and, recognition, from, the, government, and, insufficient, training, and, operational, budgets]), verbo([have]), complemento([made, 'Health', 'Council', largely, a, forum, for, consultation])]). relacion([sujeto(['Our', conclusions, 'highlight,', that, among, other, 'issues,', 'Health', 'Councils', need, to]), verbo([have]), complemento([the, legal, authority, to, act, independently, to, promote, government, 'accountability,', membership, guidelines, need, to, be, revised, in, order, include, members, of, marginalized, 'groups,', and, better, training, of, civil, society, representatives, is, required, to, help, them, make, more, informed, decisions])]). relacion([sujeto(['According', to, variations, in, antler, 'size,', it]), verbo([has]), complemento([been, classified, into, three, 'subspecies,', namely, 'Western', '(', 'R'])]). relacion([sujeto(['For', planning, effective, ex, situ, and, in, situ, conservation, of, a, 'wide-ranging', species, in, different, bioclimatic, regions, and, in, wildlife, 'forensic,', the, use, of, genetic, characterization, in, defining, 'morpho/ecotypes']), verbo([has]), complemento([been, suggested, because, of, the, geographic, clines, and, reproductive, isolation])]). relacion([sujeto(['In', spite, of, these, 'morphotypes,', very, little, is, known, about, the, genetic, characteristics, of, the, three, 'subspecies,', hence, no, strict, 'subspecies-based', breeding, plan, for]), verbo([retaining]), complemento([the, evolutionary, characteristics, in, captive, populations, for, subsequent, 're-introduction', is, available, except, for, a, few, studies])]). relacion([sujeto(['We']), verbo([suggest]), complemento([the, need, of, sorting, these, three, subspecies, using, different, molecular, mtDNA, markers, in, zoos, for, captive, breeding, purposes, so, as, to, retain, the, genetic, diversity, of, the, separate, geographic, clines, and, to, use, a, 'subspecies-specific', 'fixed-state', nucleotide, to, assess, the, extent, of, poaching, to, avoid, any, population, demography, stochastically, in, 'India'])]). relacion([sujeto(['It', is, now, well, appreciated, that, anaphylatoxins, not, only]), verbo([act]), complemento([as, 'pro-inflammatory', mediators, but, as, immunoregulatory, molecules, that, control, the, activation, status, of, cells, and, tissue, at, several, levels])]). relacion([sujeto(['Likewise,', 'C3b/iC3b', is, more, than, the, opsonizing, fragment, that, facilitates, engulfment, and, destruction, of]), verbo([targets]), complemento([by, phagocytes])]). relacion([sujeto(['Furthermore,', we, discuss, the, control, of, 'anaphylatoxin-mediated', activation, of, dendritic, cells, and, allergic, effector, cells, by, adaptive, immune, mechanisms, that]), verbo([involve]), complemento(['allergen-specific', 'IgG1', antibodies, and, plasma, or, regulatory, 'T', 'cell-derived', 'IL-10', production])]). relacion([sujeto(['These', proteins]), verbo([act]), complemento([as, mediators, of, host, defense, and, participate, in, maintenance, of, tissue, homeostasis])]). relacion([sujeto(['They']), verbo([bind]), complemento([to, conserved, 'pathogen-specific', structures, and, altered, 'self-antigens', and, form, complexes, with, the, pentraxins, to, modulate, innate, immune, functions])]). relacion([sujeto(['All', molecules, exhibit, distinct, expression, in, different, tissue, 'compartments,', but, all, are]), verbo([found]), complemento([to, a, varying, degree, in, the, circulation])]). relacion([sujeto(['A', common, feature, of, these, molecules, is, their, ability, to]), verbo([interact]), complemento([with, a, set, of, serine, proteases, named, 'MASPs', '(', 'MASP-1,', 'MASP-2,', and, 'MASP-3)'])]). relacion([sujeto(['MASP-1', and, -, 2]), verbo([trigger]), complemento([the, activation, of, the, lectin, pathway, and, 'MASP-3', may, be, involved, in, the, activation, of, the, alternative, pathway, of, complement])]). relacion([sujeto(['Furthermore,', 'MASPs']), verbo([mediate]), complemento([processes, related, to, 'coagulation,', bradykinin, 'release,', and, endothelial, and, platelet, activation])]). relacion([sujeto(['Variant', alleles, affecting, expression, and, structure, of, the, proteins]), verbo([have]), complemento([been, associated, with, a, variety, of, infectious, and, 'non-infectious', 'diseases,', most, commonly, as, disease, modifiers])]). relacion([sujeto(['Physiologically,', the, intravascular, innate, immune, system]), verbo([acts]), complemento([as, a, purging, system, that, identifies, and, removes, foreign, substances, leading, to, thromboinflammatory, 'responses,', tissue, 'remodeling,', and, repair])]). relacion([sujeto(['It', is, also, a, key, contributor, to, the, adverse, effects, observed, in, many, diseases, and, therapies]), verbo([involving]), complemento([biomaterials, and, therapeutic, 'cells/organs'])]). relacion([sujeto(['Activation', of, the, intravascular, innate, immune, system, in, vivo]), verbo([leads]), complemento([to, thromboinflammation, that, can, be, activated, by, several, of, the, 'system\'s', pathways, and, that, initiates, repair, after, tissue, damage, and, leads, to, adverse, reactions, in, several, disorders, and, treatment, modalities])]). relacion([sujeto(['In', order, to, avoid, some, of, these, obstacles, we]), verbo([have]), complemento([developed, specialized, human, whole, blood, models, that, allow, investigation, of, the, 'cross-talk', between, the, various, cascade, systems, and, the, blood, cells])]). relacion([sujeto(['We', in, particular, stress, that, platelets, are]), verbo([involved]), complemento([in, these, interactions, and, that, the, lectin, pathway, of, the, complement, system, is, an, emerging, part, of, innate, immunity, that, interacts, with, the, 'contact/coagulation', system])]). relacion([sujeto(['As', a, representative, photocatalyst, for, photoelectrochemical, solar, water, 'splitting,', 'TiO2']), verbo([has]), complemento([been, intensively, studied, but, most, researches, have, focused, on, the, rutile, and, anatsase, phases, because, 'brookite,', another, important, crystalline, polymorph, of, 'TiO2,', rarely, exists, in, nature, and, is, difficult, to, synthesize])]). relacion([sujeto(['H:brookite', shows, highly, improved, 'PEC', properties, with, excellent, 'stability,']), verbo([enhanced]), complemento(['photocurrent,', and, significantly, high, 'Faradaic', efficiency, for, overall, solar, water, splitting])]). relacion([sujeto(['At', the, interstitial, doping, site, that]), verbo([has]), complemento([minimum, formation, 'energy,', the, hydrogen, atoms, act, as, shallow, donors, and, exist, as, 'H(+)'])]). relacion([sujeto([which]), verbo([has]), complemento([the, minimum, formation, energy, among, three, states, of, hydrogen, '(', 'H(+)'])]). relacion([sujeto(['The', calculated, density, of, states, of, 'H:brookite', shows, a, narrowed, bandgap, and, an]), verbo([increased]), complemento([electron, density, compared, to, the, pristine, brookite])]). relacion([sujeto(['The', combined, experimental, and, theoretical, results]), verbo([provide]), complemento([frameworks, for, the, exploration, of, the, 'PEC', properties, of, doped, brookite, and, extend, our, knowledge, regarding, the, undiscovered, properties, of, brookite, of, 'TiO2'])]). relacion([sujeto(['Associated', with, this, theorem, is, the, quantitative, 'no-cloning', limit, that, sets, an, upper]), verbo([bound]), complemento([to, the, quality, of, the, generated, clones])]). relacion([sujeto(['Here,', we]), verbo([report]), complemento([an, experimental, demonstration, of, probabilistic, cloning, of, arbitrary, coherent, states, that, clearly, surpasses, the, 'no-cloning', limit])]). relacion([sujeto(['Moreover,', since, successful, cloning, events, are, 'heralded,', our, scheme]), verbo([has]), complemento([the, potential, to, be, adopted, in, quantum, 'repeater,', teleportation, and, computing, applications])]). relacion([sujeto(['The', microbial, transformation, of, polyphenols, in, gut, is, poorly, 'characterized,', 'where,', these, polyphenols, may]), verbo([act]), complemento([as, promoting, factors, for, proliferation, of, beneficial, gut, inhabitants, and, inhibiting, the, pathogenic, species])]). relacion([sujeto(['There', is, some, evidence, that]), verbo([suggests]), complemento(['WPL', placements, in, international, settings, are, beneficial, for, 'students\'', 'learning,', and, personal, and, professional, development])]). relacion([sujeto(['Individual', 'semi-structured', interviews, were, conducted, with, nine, graduates, who]), verbo([participated]), complemento([in, the, 'Vietnam', placement, when, they, were, final, year, occupational, therapy, students])]). relacion([sujeto(['Interviews', were, 'audio-recorded,']), verbo([transcribed]), complemento([verbatim, and, individually, analysed, to, identify, key, themes])]). relacion([sujeto(['Participants', indicated, that, the, 'Vietnam', placement, enabled, them, to, develop, their, 'resourcefulness,', 'resilience,', reasoning, 'skills,', cultural, 'competence,', confidence, and, 'independence,', beyond, what, they, felt, would]), verbo([have]), complemento([achieved, on, a, domestic, placement])]). relacion([sujeto(['For', these, reason, 'these participants']), verbo([found]), complemento([the, placement, a, beneficial, and, worthwhile, experience])]). relacion([sujeto(['There', is, little, evidence, to, direct, health, systems, toward]), verbo([providing]), complemento([efficient, interventions, to, address, medical, 'errors,', defined, as, an, unintended, act, of, omission, or, commission, or, one, not, executed, as, intended, that, may, or, may, not, cause, harm, to, the, patient, but, does, not, achieve, its, intended, outcome])]). relacion([sujeto(['However,', health, system, improvement, interventions, should, be, treated, similarly, to, individual, medical, interventions, and, undergo, rigorous, economic, evaluation, to]), verbo([provide]), complemento([actionable, evidence, to, guide, 'policy-makers', in, decisions, of, resource, allocation, for, improvement, activities, among, other, competing, demands, for, 'health-care', resources])]). relacion([sujeto(['These', preliminary, findings]), verbo([suggest]), complemento([that, both, interventions, can, induce, improvements, in, quality, of, 'life,', functional, capacity, and, selected, cardiovascular, disease, risk, factors])]). relacion([sujeto(['The', 'LVHIIT', program, was, well, tolerated, by, the, participants, and, our, results]), verbo([suggest]), complemento([that, 'LVHIIT', is, the, preferred, modality, to, improve, fitness, '(', 6, 'MWT);', it, remains, to, be, seen, which, intervention, elicits, the, most, clinically, relevant, outcomes, for, patients])]). relacion([sujeto(['A', larger, sample, size, with, a, control, group, is]), verbo([required]), complemento([to, confirm, the, significance, of, these, findings])]). relacion([sujeto(['Yet,', very, limited, research]), verbo([has]), complemento([been, done, on, this, tribunal])]). relacion([sujeto(['Failure', to, address, the, spread, of, 'TB', and, to]), verbo([provide]), complemento([quality, treatment, to, all, affected, populations, constitutes, a, public, health, and, human, rights, emergency, that, demands, action, and, accountability])]). relacion([sujeto(['Backround:', 'Abnormal', expression, of, 'CXC', chemokine, receptor, 1, '(', 'CXCR1)']), verbo([has]), complemento([shown, the, ability, to, promote, tumor, 'angiogensis,', invasion, and, metastasis, in, several, cancers])]). relacion([sujeto(['Combining', 'CXCR1', expression, with, current, 'TNM', staging, system, could]), verbo([lead]), complemento([to, better, risk, stratification, and, more, accurate, prognosis, for, gastric, cancer, patients])]). relacion([sujeto(['Here,', we, demonstrate, that, 'IFNγ']), verbo([promotes]), complemento(['AML', blasts, to, act, as, effector, cells, within, the, context, of, antibody, therapy])]). relacion([sujeto(['Treatment', with, 'IFNγ', drove, 'AML', blasts, toward, a, more, differentiated, 'state,', wherein, they, showed]), verbo([increased]), complemento([expression, of, the, 'M1-related', markers, 'HLA-DR', and, 'CD86,', as, well, as, of, 'FcγRI,', which, mediates, effector, responses, to, therapeutic, antibodies])]). relacion([sujeto(['Importantly,', 'IFNγ', was, able, to, 'up-regulate', 'CD38,', the]), verbo([target]), complemento([of, the, therapeutic, antibody, daratumumab])]). relacion([sujeto(['Because', the, antigen, '(', 'CD38)', and, effector, receptor, '(', 'FcγRI)', were, both, simultaneously, 'up-regulated', on, the, 'AML', 'blasts,', we, tested, whether, 'IFNγ', treatment, of, the, 'AML', cell, lines, 'THP-1', and, 'MV4-11', could]), verbo([stimulate]), complemento([them, to, target, one, another, after, the, addition, of, daratumumab])]). relacion([sujeto(['Results', showed, that, 'IFNγ', significantly]), verbo([increased]), complemento(['daratumumab-mediated', 'cytotoxicity,', as, measured, both, by, '(', 51, ')', 'Cr', release, and, lactate, dehydrogenase, release, assays])]). relacion([sujeto(['We', also]), verbo([found]), complemento([that, the, combination, of, 'IFNγ', and, activation, of, 'FcγR', led, to, the, release, of, granzyme, 'B', by, 'AML', cells])]). relacion([sujeto(['Finally,', using, a, murine, 'NSG', model, of, subcutaneous, 'AML,', we]), verbo([found]), complemento([that, treatment, with, 'IFNγ', plus, daratumumab, significantly, attenuated, tumor, growth])]). relacion([sujeto(['Accumulation', of, anthropogenic, litter, '(', 'AL)', on, marine, beaches, and, its, ecological, effects]), verbo([have]), complemento([been, a, major, focus, of, research])]). relacion([sujeto(['Recent', studies]), verbo([suggest]), complemento(['AL', is, also, abundant, in, freshwater, 'environments,', but, much, less, research, has, been, conducted, in, freshwaters, relative, to, oceans])]). relacion([sujeto(['The', 'Adopt-a-BeachTM', '(', 'AAB)', 'program,', administered, by, the, 'Alliance', for, the, 'Great', 'Lakes,', organizes, volunteers, to]), verbo([act]), complemento([as, citizen, scientists, by, collecting, and, maintaining, data, on, 'AL', abundance, on, 'Great', 'Lakes', beaches])]). relacion([sujeto(['However,', 'AAB', records]), verbo([have]), complemento([not, yet, been, used, to, examine, patterns, of, 'AL', density, and, composition, among, beaches, of, all, different, substrate, types, '(', e])]). relacion([sujeto(['We']), verbo([found]), complemento([that, most, 'AL', on, beaches, are, consumer, goods, that, most, likely, originate, from, beach, visitors, and, nearby, urban, 'environments,', rather, than, activities, such, as, 'shipping,', 'fishing,', or, illegal, dumping])]). relacion([sujeto(['Finally,', we]), verbo([found]), complemento([that, 'AL', abundance, is, lowest, during, the, 'summer,', between, the, 'US', holidays, of, 'Memorial', 'Day', '(', last, 'Monday', in, 'May)', and, 'Labor', 'Day', '(', first, 'Monday', in, 'September)', at, the, urban, 'beaches,', while, other, beaches, showed, no, seasonality])]). relacion([sujeto(['This', research, is, a, model, for, utilizing, datasets, collected, by, volunteers]), verbo([involved]), complemento([in, citizen, science, 'programs,', and, will, contribute, to, 'AL', management, by, offering, priorities, for, 'AL', types, and, locations, to, maximize, 'AL', reduction])]). relacion([sujeto(['Nucleotides', are, key, subunits, for, nucleic, acids, and]), verbo([provide]), complemento([energy, for, intracellular, metabolism])]). relacion([sujeto(['They', can, also, be]), verbo([released]), complemento([from, cells, to, act, physiologically, as, extracellular, messengers, or, pathologically, as, danger, signals])]). relacion([sujeto(['Extracellular', nucleotides]), verbo([stimulate]), complemento([membrane, receptors, in, the, 'P2', and, 'P1', family])]). relacion([sujeto(['P2X', are, 'ATP-activated', cation, 'channels;', 'P2Y', and, 'P1', are, 'G-protein', coupled, receptors]), verbo([activated]), complemento([by, 'ATP,', 'ADP,', 'UTP,', and, 'UDP', in, the, case, of, 'P2', or, adenosine, for, 'P1'])]). relacion([sujeto(['Renal', cells, also]), verbo([express]), complemento([ectonucleotidases, that, rapidly, hydrolyze, extracellular, nucleotides])]). relacion([sujeto(['Purinergic', signaling, also]), verbo([regulates]), complemento([immune, cell, function, by, modulating, the, synthesis, and, release, of, various, cytokines, such, as, 'IL1-β', and, 'IL-18', as, part, of, inflammasome, activation])]). relacion([sujeto(['Kidney', tissue, injury]), verbo([causes]), complemento([a, localized, increase, in, 'ATP', 'concentration,', and, sustained, activation, of, 'P2', receptors, can, lead, to, renal, 'glomerular,', 'tubular,', and, vascular, cell, damage])]). relacion([sujeto(['Purinergic', receptors, also]), verbo([regulate]), complemento([the, activity, and, proliferation, of, 'fibroblasts,', promoting, both, inflammation, and, fibrosis, in, chronic, disease])]). relacion([sujeto(['We', focus, predominantly, on, the, 'P2X7', 'receptor,', discussing, why, antagonists]), verbo([have]), complemento([so, far, disappointed, in, clinical, trials, and, how, advances, in, our, understanding, of, purinergic, signaling, might, help, to, reposition, these, compounds, as, potential, treatments, for, renal, disease])]). relacion([sujeto(['It', is, related, with, genomic, 'instability,', which]), verbo([has]), complemento([been, shown, to, occur, in, the, presence, of, autophagy, deficiency])]). relacion([sujeto(['Yet,', the, mechanism, that]), verbo([triggers]), complemento([genomic, instability, and, senescence, from, a, condition, of, autophagy, deficiency, remains, unknown])]). relacion([sujeto(['We', also, evaluated, membrane, leakage]), verbo([induced]), complemento([by, 'BA', in, liposomes, and, giant, unilamellar, vesicles])]). relacion([sujeto(['By', destabilizing, lipid, bilayers, of, mitochondria, and, 'lysosomes,', 'BA']), verbo([triggers]), complemento([the, misbalance, in, the, 'mitochondrial-lysosomal', axis, leading, to, perceived, autophagy, 'impairment,', 'lipofuscinogenesis,', genomic, instability, and, cell, senescence])]). relacion([sujeto(['The', progressive, accumulation, of, mitochondria, and, 'lipofuscin,', which, comes, from, imperfect, mitophagy]), verbo([triggered]), complemento([by, 'BA,', provides, a, continuous, source, of, reactive, species, further, damaging, lysosomes, and, leading, to, cell, aging])]). relacion([sujeto(['This', work]), verbo([reveals]), complemento([that, the, initial, trigger, of, cell, senescence, can, be, the, physical, damage, in, the, membranes, of, lysosomes, and, mitochondria])]). relacion([sujeto(['This', concept, will, help, in, the, search, of, new, drugs, that]), verbo([act]), complemento([as, 'senescence-inductors'])]). relacion([sujeto(['Here,', we]), verbo([found]), complemento([that, 'oxygen-glucose', deprivation, '(', 'OGD)-induced', autophagy, was, suppressed, by, exogenous, 'Act', 'A', in, a, 'concentration-dependent', manner, and, enhanced, by, 'Act', 'A/Smads', pathway, inhibitor, '(', 'ActRIIA-Ab)', in, neuronal, 'PC12', cells])]). relacion([sujeto(['These', results, indicate, that, 'Act', 'A/Smads', pathway, negatively]), verbo([regulates]), complemento([autophagy, in, 'OGD-treated', 'PC12', cells])]). relacion([sujeto(['In', 'addition,', we]), verbo([found]), complemento([that, 'c-Jun', 'N-terminal', kinase, '(', 'JNK)', and, p38, 'mitogen-activated', protein, '(', 'MAP)', kinase, pathways, are, involved, in, the, 'OGD-induced', autophagy])]). relacion([sujeto(['The', activation, of, 'JNK', and, p38, 'MAPK', pathways, in, 'OGD-treated', 'PC12', cells, was]), verbo([suppressed]), complemento([by, exogenous, 'Act', 'A', and, enhanced, by, 'ActRIIA-Ab'])]). relacion([sujeto(['Together,', our, results]), verbo([suggest]), complemento([that, 'Act', 'A/Smads', signaling, pathway, negatively, regulates, 'OGD-induced', autophagy, via, suppression, of, 'JNK', and, p38, 'MAPK', pathways, in, neuronal, 'PC12 cells'])]). relacion([sujeto(['This']), verbo([leads]), complemento([to, improper, assessments, of, biochemical, limitations, that, limit, the, accuracy, of, the, model, predictions])]). relacion([sujeto(['Japanese', encephalitis, virus, '(', 'JEV)', is, a, pathogenic]), verbo([cause]), complemento([of, 'Japanese', 'Encephalitis', '(', 'JE),', which, is, a, zoonotic, disease, transmitted, by, mosquitoes, and, amplified, by, pigs])]). relacion([sujeto(['Infection', of, 'JEV', may]), verbo([lead]), complemento([to, severe, neurological, 'sequelae,', even, death, in, humans, and, reproductive, disorders, in, pigs])]). relacion([sujeto(['We']), verbo([have]), complemento([previously, reported, that, 'DNA', vaccine, 'pCAG-JME,', expressing, 'prM-E', proteins, of, 'JEV,', is, effective, in, mice, through, intramuscular, injection, '(', 'IM)'])]). relacion([sujeto(['As', compared, with, 'IM,', 'EP-mediated', vaccination, markedly]), verbo([increased]), complemento([the, expression, of, immunogen, in, the, injection, site, and, induced, a, 'dose-', and, 'time-dependent', immune, response])]). relacion([sujeto([100, '%', survival, rate, was, observed, in, groups, vaccinated, with, doses, ranged, from, 10, to, 100, 'μg,', indicating, that, 10, μg, of, 'DNA', with, 'EP', for, individual, was, enough, for]), verbo([inducing]), complemento([effective, protection, in, mice])]). relacion([sujeto(['Notably,', the, 'prM-E', antigens, also]), verbo([induced]), complemento([high, antibody, response, in, 'pig,', while, the, neutralizing, antibody, titer, achieved, 1, :, 320])]). relacion([sujeto(['Our', results]), verbo([suggested]), complemento([that, 'EP-mediated', 'DNA', immunization, might, act, as, an, effective, strategy, against, 'JEV,', at, least, in, 'pig,', and, that, 'EP', has, a, potential, application, prospect, in, 'DNA', vaccination])]). relacion([sujeto(['Mitochondrion', dysfunction]), verbo([has]), complemento([been, correlated, with, numerous, metabolic, diseases, such, as, obesity, and, type, 2, diabetes])]). relacion([sujeto(['MicroRNAs', are, 'non-coding', 'RNAs', that]), verbo([have]), complemento([emerged, as, key, regulators, of, cell, metabolism])]). relacion([sujeto(['The', microRNAs]), verbo([act]), complemento([as, central, regulators, of, metabolic, gene, networks, by, leading, to, the, degradation, of, their, target, messenger, 'RNA', or, repression, of, protein, translation])]). relacion([sujeto(['Many', fish, that, are, exposed, to, a, threat]), verbo([release]), complemento([disturbance, 'cues,', which, are, chemicals, that, alert, conspecifics, to, the, presence, of, the, threat])]). relacion([sujeto(['The']), verbo([release]), complemento([of, disturbance, cues, has, been, well, demonstrated, in, various, species, of, 'laboratory-reared', fish])]). relacion([sujeto(['Migratory', fish, species, often, exhibit]), verbo([increased]), complemento([cortisol, levels, and, are, exposed, to, numerous, stressors, during, their, 'migrations,', which, could, trigger, the, release, of, disturbance, cues])]). relacion([sujeto(['gorbuscha)', to, the, odours, of, disturbed, and, undisturbed, conspecifics, to, determine, whether, these, fish]), verbo([release]), complemento([disturbance, cues, following, exposure, to, a, simulated, stressor])]). relacion([sujeto(['We']), verbo([found]), complemento([that, sockeye, salmon, avoid, the, odour, of, disturbed, 'conspecifics,', whereas, pink, salmon, do, not])]). relacion([sujeto(['Avoidance', occurred, in, both, female, and, male, sockeye, 'salmon,', and, was]), verbo([associated]), complemento([with, an, increase, in, plasma, cortisol, levels, in, 'females,', but, not, in, males])]). relacion([sujeto(['We', also]), verbo([found]), complemento([no, behavioural, response, to, 'water-borne', 'cortisol,', which, suggests, this, chemical, does, not, act, as, an, exogenous, disturbance, cue, in, sockeye, salmon])]). relacion([sujeto(['Studies']), verbo([have]), complemento([been, mounting, in, support, of, the, finding, that, plants, release, aerobic, methane, '(', 'CH4', ')', ',', and, that, these, emissions, are, increased, by, both, 'short-term', and, 'long-term', environmental, stress])]). relacion([sujeto(['Both', 'shade-intolerant', sunflower, and, 'shade-tolerant', chrysanthemum, were, investigated, for, the]), verbo([release]), complemento([of, aerobic, 'CH4', 'emissions,', using, either, low, or, high, light, 'intensity,', and, varying, light, 'quality,', including, 'control,', low, or, normal, 'red:far-red', ratio, '(', 'R:FR),', and, low, or, high, levels, of, 'blue,', to, discern, the, relationship, between, light, and, 'CH4', emissions])]). relacion([sujeto(['It', was]), verbo([found]), complemento([that, low, levels, of, light, act, as, an, environmental, 'stress,', facilitating, 'CH4', release, from, both, species])]). relacion([sujeto(['R:FR', and, blue, lights]), verbo([increased]), complemento([emissions, under, low, 'light,', but, the, results, varied, with, 'species,', providing, evidence, that, both, light, quantity, and, quality, regulate, 'CH4', emissions])]). relacion([sujeto(['Moreover,', emissions]), verbo([decreased]), complemento([with, age, as, plants, acclimated, to, environmental, conditions])]). relacion([sujeto(['The', conformational, flexibility, and, hydrophobicity, of, the, spacer, group, can, be, effectively, tailored, through]), verbo([regulating]), complemento([the, spacer, 'length,', leading, to, the, fine, control, of, the, topologies, and, subsequent, hierarchical, 'self-assemblies', of, '[', 'M-n-M](2+)@2[DBS](-)'])]). relacion([sujeto(['Vesicles', are, primarily, fabricated, by, '[', 'M-n-M](2+)@2[DBS](-),', and, then, successively, fused, into, vesicle, 'clusters,', 'nanotubes,', and, planar, 'bilayers,', whose, bilayer, curvatures, are, gradually, 'decreased,', with]), verbo([increasing]), complemento([spacer, length])]). relacion([sujeto(['Furthermore,', stable, aqueous, 'two-phase', systems, '(', 'ATPSs)', that, spontaneously, formed, via, vesicle, fusion, in, the, solutions, of, '[', 'M-n-M](2+)@2[DBS](-)', '(', n, =, 6, ',', 10, ')', can]), verbo([act]), complemento([as, functional, supramolecular, systems, in, the, isolation, and, purification, of, 'oil-soluble', biomaterials])]). relacion([sujeto(['Chlorination', of, all, betacyanins, that, are, decarboxylated, at, carbon, 'C-17', results, in, an]), verbo([increase]), complemento([of, their, retention, times])]). relacion([sujeto(['The', elaborated, method, for, determination, of, chlorinated, pigments, enabled, analysis, of, a, chlorinated, red, beet, root, extract, that, was, submitted, to, the, 'MPO/H2O2/Cl(-)', system]), verbo([acting]), complemento([under, 'inflammation-like', conditions, '(', pH, 5, ')'])]). relacion([sujeto(['This', indicates, a, promising, possibility, for, measurement, of, these, chlorinated, pigments, as, indicators, of, specific, inflammatory, states, wherein, betacyanins, and, decarboxylated, betacyanins]), verbo([act]), complemento([as, hypochlorite, scavengers])]). relacion([sujeto(['Ten', patients, '(', 8.4, '%', ')', revealed, to]), verbo([have]), complemento(['MK'])]). relacion([sujeto(['All', 'MK-positive', '(', 'MK(+))', 'AML', were]), verbo([associated]), complemento([with, complex, cytogenetic, abnormalities, and, belonged, to, the, cytogenetic, 'adverse-risk', group])]). relacion([sujeto(['In', 'conclusion,', 'MK', did, not]), verbo([act]), complemento([as, an, adverse, prognostic, factor, in, childhood, de, novo, 'AML'])]). relacion([sujeto(['Allogeneic', 'HSCT', might]), verbo([have]), complemento([contributed, to, the, excellent, outcome, of, 'MK(+)', childhood, de, novo, 'AML'])]). relacion([sujeto(['Significant', breakthroughs, in, the, field, of, injury, prevention, and, childhood, safety]), verbo([have]), complemento([occurred, during, the, past, 'half-century'])]). relacion([sujeto(['Youth', firearm, injury, remains, a, major]), verbo([cause]), complemento([of, death, and, disability, in, adolescents])]). relacion([sujeto(['Despite', a, lack, of, robust, injury, prevention, research, on, the, 'topic,', the, development, of, novel, approaches, to, access, and, examine, firearm, injury, data, is]), verbo([leading]), complemento([to, exploration, of, public, health, approaches, to, reduce, these, injuries])]). relacion([sujeto(['Finally,', despite, legislative, and, educational, efforts, surrounding, child, passenger, safety, and, graduated, driver, license, 'laws,', motor, vehicle, crashes, are, still, a]), verbo([leading]), complemento([cause, of, injury, for, both, children, and, 'adolescents;', 'however,', research, on, these, laws, holds, the, opportunity, for, significant, reduction, in, injuries])]). relacion([sujeto(['Gemini', analogs, of, 'calcitriol,', characterized, by, the, extension, of, the, 'C21-methyl', group, of, calcitriol, with, a, second, 'chain,']), verbo([act]), complemento([as, agonists, of, the, vitamin, 'D', receptor, '(', 'VDR)'])]). relacion([sujeto(['BXL0124']), verbo([acts]), complemento([as, a, more, potent, 'VDR', agonist, than, its, 19, -, nor, counterpart, by, activating, 'VDR-mediated', transcription, at, lower, concentrations])]). relacion([sujeto(['Despite']), verbo([increased]), complemento([leptin, concentrations, during, 'pregnancy,', fat, mass, and, food, intake, are, increased])]). relacion([sujeto(['Central', leptin, injection, prior, to, a, 'GTT']), verbo([lead]), complemento([to, lowered, basal, insulin, concentrations, and, impaired, glucose, tolerance, in, nonpregnant, female, 'rats,', whereas, the, same, doses, of, leptin, had, no, significant, effect, on, glucose, tolerance, in, day, 14, pregnant, 'rats,', indicating, 'that,', similar, to, the, satiety, actions, of, 'leptin,', the, effects, of, leptin, on, glucose, homeostasis, are, suppressed, during, pregnancy])]). relacion([sujeto(['Furthermore,', in, the, arcuate, nucleus, and, ventromedial, and, dorsomedial, nuclei, of, the, 'hypothalamus,', comprising, three, 'leptin-sensitive', 'areas,', there, was, no, evidence, that, leptin]), verbo([induced]), complemento(['Akt', phosphorylation, despite, significant, increases, in, 'phospho-STAT3,', suggesting, that, leptin, does, not, act, through, 'phospho-Akt', in, these, areas, in, female, rats])]). relacion([sujeto(['Despite', 'ID', talking, and, 'ID', singing, being, very, similar, in, physical, 'properties,', infants, differentially]), verbo([respond]), complemento([to, each, of, them])]). relacion([sujeto(['We']), verbo([found]), complemento([that, during, 'ID', 'talking,', infants, displayed, a, significantly, higher, number, of, visual, 'contacts,', 'vocalizations,', and, body, movements, than, during, 'ID', singing])]). relacion([sujeto(['Our', results]), verbo([suggest]), complemento([that, 'ID', talking, provides, infants, with, specific, cues, that, allow, them, not, only, to, react, to, mother, 'stimulation,', but, also, to, act, toward, 'them,', displaying, a, rudimentary, version, of, 'turn-taking', behavior])]). relacion([sujeto(['Endophytic', bacteria, may]), verbo([act]), complemento([individually, or, in, consortia, in, controlling, certain, plant, diseases])]). relacion([sujeto(['Exploring', the, internal, tissues, of, plants, growing, in, diverse, soil, environments, could, be, a, way, to]), verbo([find]), complemento([potential, candidates, for, biocontrol, agents])]). relacion([sujeto(['Animal', and, human, studies]), verbo([have]), complemento([consistently, demonstrated, that, cortical, regions, are, important, for, pain, perception, and, 'pain-related', emotional, changes])]). relacion([sujeto(['Studies', of, the, anterior, cingulate, cortex, '(', 'ACC)']), verbo([have]), complemento([shown, that, adult, cortical, synapses, can, be, modified, after, peripheral, 'injuries,', and, 'long-term', changes, at, synaptic, level, may, contribute, to, 'long-lasting', suffering, in, patients])]). relacion([sujeto(['It', also, explains, why, chronic, pain, is, resistant, to, conventional, analgesics, that]), verbo([act]), complemento([by, inhibiting, synaptic, transmission])]). relacion([sujeto(['Insular', cortex, '(', 'IC),', another, critical, cortical, 'area,', is]), verbo([found]), complemento([to, be, highly, plastic, and, can, undergo, 'long-term', potentiation, '(', 'LTP)', after, injury])]). relacion([sujeto(['Inhibiting', 'IC', 'LTP', reduces, behavioral, sensitization]), verbo([caused]), complemento([by, injury])]). relacion([sujeto(['While', not, minimizing, 'Forbes', suffering, throughout, these, 'events,', 'McKnight', should, be, appropriately]), verbo([recognized]), complemento([for, his, initiative, and, 'contributions,', which, far, exceeded, those, of, 'Forbes'])]). relacion([sujeto(['LncRNA-ROR']), verbo([has]), complemento([been, reported, to, be, involved, in, many, kinds, of, human, cancers])]). relacion([sujeto(['However,', whether, 'LncRNA-ROR', is]), verbo([involved]), complemento([in, gallbladder, cancer, progression, remains, largely, unknown])]). relacion([sujeto(['We']), verbo([found]), complemento([that, 'LncRNA-ROR', expression, level, was, upregulated, in, gallbladder, cancer, tissues, '(', 'P < 0'])]). relacion([sujeto([5, ')', and, was, significantly]), verbo([associated]), complemento([with, tumor, sizes, '(', 'P < 0'])]). relacion([sujeto(['High', expression, of, 'LncRNA-ROR', was, significantly]), verbo([associated]), complemento([with, poor, prognosis, in, gallbladder, cancer, patients, '(', 'P < 0'])]). relacion([sujeto(['Moreover,', knockdown, of, 'LncRNA-ROR']), verbo([inhibited]), complemento([cell, 'proliferation,', 'migration,', and, invasion])]). relacion([sujeto(['The', 'epithelial-mesenchymal', transition, '(', 'EMT)', phenotype]), verbo([induced]), complemento([by, 'TGF-β1', was, reversed, after, 'LncRNA-ROR', knocking, down, in, 'SGC-996', and, 'Noz', cells])]). relacion([sujeto(['LncRNA-ROR', plays, an, important, role, in, the, development, of, gallbladder, cancer, and]), verbo([mediates]), complemento([the, 'EMT', in, gallbladder, cancer])]). relacion([sujeto(['LncRNA-ROR', might]), verbo([act]), complemento([as, a, marker, of, prognosis, and, therapeutic, target, for, gallbladder, cancer])]). relacion([sujeto(['Lead', compounds, that]), verbo([target]), complemento([tubulin, are, being, developed, as, agents, against, the, human, malaria, 'parasite,', 'Plasmodium', falciparum])]). relacion([sujeto(['It', is, important, to, define, the]), verbo([binding]), complemento([sites, of, these, molecules, on, the, tubulin, 'dimer:', 'Taxol,', 'Vinca', domains, or, novel, binding, 'pockets;', 'however,', extraction, of, native, parasite, tubulin, is, difficult])]). relacion([sujeto(['This']), verbo([report]), complemento([aims, to, develop, assays, that, allow, the, rapid, assessment, of, binding, sites, of, compounds, on, the, tubulin, dimer])]). relacion([sujeto(['We']), verbo([have]), complemento([developed, a, simple, growth, 'assay,', using, a, combination, of, two, 'anti-microtubule', drugs, that, have, overlapping, binding, 'sites,', to, study, whether, the, two, drugs, act, in, 'synergistic,', antagonistic, or, neutral, manner])]). relacion([sujeto(['Additionally,', 'Molecular', docking, was, used, to, predict, the]), verbo([binding]), complemento([sites, of, the, drugs])]). relacion([sujeto(['The', combination, assay, shows, antagonistic, interactions, between, drugs, having, overlapping]), verbo([binding]), complemento([sites])]). relacion([sujeto(['In', 'contrast,', drugs, that, do, not]), verbo([bind]), complemento([to, overlapping, sites, show, no, interactions, or, synergism, in, this, combination, assay])]). relacion([sujeto(['Molecular', docking, predictions, show, that, 'indeed,', drugs, with, antagonistic, interactions, in, the, growth, assay, do]), verbo([bind]), complemento([to, overlapping, sites])]). relacion([sujeto(['These', two, assays, can, be, a, simple, preliminary, screen, for, the]), verbo([binding]), complemento([sites, of, novel, 'anti-tubulin', compounds, being, developed, for, malaria, therapeutics])]). relacion([sujeto(['Antidepressant', drugs, are, not, acute, analgesics, but]), verbo([require]), complemento([a, chronic, treatment, to, relieve, neuropathic, 'pain,', which, suggests, the, recruitment, of, secondary, downstream, mechanisms, as, well, as, 'long-term', molecular, and, neuronal, plasticity])]). relacion([sujeto(['Mechanistic', hypotheses]), verbo([have]), complemento([implied, the, recruitment, of, noradrenergic, descending, pathways, as, well, as, the, peripheral, recruitment, of, noradrenaline, from, sympathetic, fibers, sprouting, into, dorsal, root, 'ganglia;', and, importance, of, both, α2, and, β2, adrenoceptors, have, been, reported])]). relacion([sujeto(['These', monoamine, 're-uptake', inhibitors, may, also, indirectly]), verbo([act]), complemento([as, 'anti-proinflammatory', cytokine, 'drugs;', and, their, therapeutic, action, requires, the, opioid, 'system,', particularly, the, mu, '(', 'MOP)', 'and/or', delta, '(', 'DOP)', opioid, receptors])]). relacion([sujeto(['Gabapentinoids,', which]), verbo([target]), complemento([the, 'voltage-dependent', calcium, channels, 'α2δ-1', 'subunit,', inhibit, calcium, 'currents,', thus, decreasing, the, excitatory, transmitter, release, and, spinal, sensitization])]). relacion([sujeto(['Gabapentinoids', also]), verbo([activate]), complemento([the, descending, noradrenergic, pain, inhibitory, system, coupled, to, spinal, α2, adrenoceptors])]). relacion([sujeto(['However,', baseline, 'MMP12', and, 'MMP13', levels, were, strongly]), verbo([associated]), complemento([with, stroke, severity, and, were, found, to, be, elevated, in, those, patients, with, the, poorest, outcomes])]). relacion([sujeto(['Interestingly,', plasma, 'MMP3', was, independent, of, baseline, stroke, characteristics, but, was]), verbo([found]), complemento([to, be, increased, in, patients, with, better, 'motor/functional', recovery, and, in, patients, with, larger, improvements, during, rehabilitation])]). relacion([sujeto(['MMPs', might]), verbo([act]), complemento([as, biologic, markers, of, recovery, during, rehabilitation, therapy, related, to, their, roles, in, both, injury, and, tissue, remodeling])]). relacion([sujeto(['Of', the, 1, ',', 0, plant, extracts, 'tested,', two, bioactive, compounds, from, 'Miliusa', sinensis, were]), verbo([found]), complemento([to, act, specifically, on, the, calcineurin, pathway, of, 'C'])]). relacion([sujeto(['The', chemical, investigation, of, the, 'GG1F1', extract]), verbo([led]), complemento([to, the, isolation, and, characterization, of, two, thiodiketopiperazine, derivatives])]). relacion([sujeto(['Both', the, compounds]), verbo([inhibited]), complemento([the, growth, of, several, bacterial, pathogens, especially, that, of, 'Staphylococcus', aureus, and, 'Streptococcus', 'pyogenes,', with, 'IC50', values, of, less, than, 10, &, 'nbsp;μM'])]). relacion([sujeto(['The', compounds, strongly]), verbo([inhibited]), complemento([biofilm, formation, in, both, the, pathogens])]). relacion([sujeto(['The', compounds, were]), verbo([found]), complemento([to, act, synergistically, with, streptomycin, while, producing, varying, effects, in, combination, with, ciprofloxacin, and, ampicillin])]). relacion([sujeto(['The', compounds]), verbo([inhibited]), complemento([bacterial, 'transcription/translation', in, 'vitro,', and, also, inhibited, staphyloxanthin, production, in, 'S'])]). relacion([sujeto(['Acidobacteria', is, one, of, the, most, abundant, phyla, in, soils, and]), verbo([has]), complemento([been, detected, in, rhizosphere, mainly, based, on, 'cultivation-independent', approaches, such, as, 16, 'S', rRNA, gene, survey])]). relacion([sujeto(['Therefore,', we, performed, several, in, vitro, tests, to, evaluate, 'Acidobacteria-plant', interactions, and, the, possible, mechanisms]), verbo([involved]), complemento([in, such, interaction])]). relacion([sujeto(['We', observed, that, 'Arabidopsis', thaliana, inoculated, with, three, strains, belonging, to, 'Acidobacteria', subdivision, 1, showed]), verbo([increase]), complemento([in, biomass, of, roots, and, shoots, as, well, as, morphological, changes, in, root, system])]). relacion([sujeto(['Our', results, indicate, that, the, plant, hormone, 'indole-3-acetic', acid, production, and, iron, acquisition, are, plausibly]), verbo([involved]), complemento([in, the, plant, and, 'Acidobacteria', interactions])]). relacion([sujeto(['Here,', we, confirm, for, the, first, time, that, 'Acidobacteria', can, actively]), verbo([interact]), complemento([with, plants, and, act, as, plant, 'growth-promoting', bacteria])]). relacion([sujeto(['Despite', its, 'prevalence,', the, basic, physiology, and, underlying, mechanisms, contributing, to, the, development, of, migraine, are, still, poorly, understood, and, development, of, new, therapeutic]), verbo([targets]), complemento([is, long, overdue])]). relacion([sujeto(['Blood', vessels, consist, of, a, variety, of, cell, types, that, both]), verbo([release]), complemento([and, respond, to, numerous, mediators, including, growth, 'factors,', 'cytokines,', adenosine, triphosphate, '(', 'ATP),', and, nitric, oxide, '(', 'NO)'])]). relacion([sujeto(['Many', of, these, mediators]), verbo([have]), complemento([actions, on, neurons, that, can, contribute, to, migraine])]). relacion([sujeto(['Conversely,', neurons]), verbo([release]), complemento([factors, such, as, norepinephrine, and, calcitonin, 'gene-related', peptide, '(', 'CGRP)', that, act, on, cells, native, to, blood, vessels])]). relacion([sujeto(['Both', normal, and, pathological, events, occurring, within, and, between, vascular, cells, could, thus]), verbo([mediate]), complemento(['bi-directional', communication, between, vessels, and, the, nervous, 'system,', without, the, need, for, changes, in, vascular, tone])]). relacion([sujeto(['Together,', the, data, discussed, will]), verbo([provide]), complemento([a, framework, by, which, vessels, can, be, viewed, as, important, potential, contributors, to, migraine, 'pathophysiology,', even, in, light, of, the, current, uncertainty, over, the, role, of, vasodilation, in, this, disorder])]). relacion([sujeto(['We', observed, that, patients, with, the, &, 'quot;G"', allele, of, rs7708392, and, the, &, 'quot;C"', allele, of, rs10036748, showed, an]), verbo([increased]), complemento([risk, of, gastric, carcinoma, '(', 'OR=', 1.335, ',', 95, '%', 'CI:', 1.021, -, 1.745, ',', 'P=', 0.035, ;, 'OR=', 1.358, ',', 95, '%', 'CI:', 1.039, -, 1.774, ',', 'P=', 0.025, ',', 'respectively)'])]). relacion([sujeto(['Conversely,', the, haplotype, &, 'quot;CT"', of, 'TNIP1', '(', 'rs7708392-rs10036748)', may]), verbo([act]), complemento([as, a, genetic, protective, factor, for, gastric, carcinoma, '(', adjusted, 'OR=', 0.731, ',', 95, '%', 'CI:', 0.552, -, 0.97, ',', 'P=', 0.03, ')'])]). relacion([sujeto(['Our', results, are, the, first, to]), verbo([suggest]), complemento([that, genetic, variation, in, 'TNIP1', gene, is, associated, with, gastric, 'carcinoma,', 'though,', this, finding, must, be, confirmed, in, other, populations, with, larger, sample, size])]). relacion([sujeto(['Consequently,', the, pathogens, are]), verbo([required]), complemento([to, regulate, their, behavior, in, response, to, environmental, cues, in, order, to, 'survive,', but, how, nutrients, control, the, virulence, in, opportunistic, pathogens, is, still, poorly, understood])]). relacion([sujeto(['Our', results, show, that]), verbo([increased]), complemento([environmental, nutrient, concentration, can, increase, the, expression, of, putative, virulence, 'genes,', chondroitinase, '(', 'cslA)', and, 'collagenase,', in, the, 'outside-host', environment, and, may, lead, to, more, rapid, fish, mortality])]). relacion([sujeto(['These', findings, address, that, the, environmental, nutrients, may]), verbo([act]), complemento([as, significant, triggers, of, virulence, gene, expression, and, therefore, contribute, to, the, interaction, between, an, environmentally, transmitted, opportunistic, pathogen, and, its, host])]). relacion([sujeto(['Ubiquitin-conjugating', enzyme, 'E2T', '(', 'UBE2T)', is, a, member, of, the, 'E2', family, that]), verbo([mediates]), complemento([the, 'ubiquitin-proteasome', system, and, regulates, gene, expression])]). relacion([sujeto(['Here,', we, identified, the, roles, of, 'UBE2T', in, 'GC', progression, and, its, potential, to]), verbo([act]), complemento([as, a, prognostic, marker, of, 'GC'])]). relacion([sujeto(['In', vitro, experiments, indicated, that, 'UBE2T']), verbo([promoted]), complemento([cell, proliferation, and, inhibited, cell, cycle, arrest])]). relacion([sujeto(['In', 'addition,', we, observed, that, 'UBE2T']), verbo([modulated]), complemento([cell, mobility, by, inducing, 'epithelial-mesenchymal', transition])]). relacion([sujeto(['Collectively,', these, findings]), verbo([suggest]), complemento([that, 'UBE2T', plays, an, important, role, in, the, tumorigenesis, of, gastric, cancer, and, could, act, as, a, potential, independent, prognostic, factor, for, cancer, therapy])]). relacion([sujeto(['The', main, focus, for, the, development, of, adenosine]), verbo([targets]), complemento([as, analgesics, to, date, has, been, 'A1Rs', due, to, its, antinociceptive, profile, in, various, preclinical, pain, models])]). relacion([sujeto(['The', usefulness, of, systemic, 'A1R', agonists, may, be, limited, by, other, effects, '(', 'cardiovascular,', 'motor),', but]), verbo([enhanced]), complemento([selectivity, for, pain, might, occur, with, partial, 'agonists,', potent, and, highly, selective, 'agonists,', or, allosteric, modulators])]). relacion([sujeto(['A2AR', agonists, exhibit, some, peripheral, pronociceptive, 'effects,', but, also]), verbo([act]), complemento([on, immune, cells, to, suppress, inflammation, and, on, spinal, glia, to, suppress, pain, signaling, and, may, be, useful, for, inflammatory, and, neuropathic, pain])]). relacion([sujeto(['Endogenous', adenosine, levels, can, be, augmented, by, inhibition, of, metabolism, '(', via, adenosine, 'kinase)', or]), verbo([increased]), complemento([generation, '(', via, 'nucleotidases),', and, these, approaches, have, implications, for, pain])]). relacion([sujeto(['Finally,', caffeine]), verbo([inhibits]), complemento(['A1-,', 'A2A-', and, 'A3Rs', with, similar, 'potency,', and, dietary, caffeine, intake, will, need, attention, in, trials, 'of:', '(', 'a)', agonists, 'and/or', modulators, acting, at, these, 'receptors,', '(', 'b)', some, pharmacological, and, herbal, 'analgesics,', and, '(', 'c)', manipulations, that, enhance, endogenous, adenosine, 'levels,', all, of, which, are, inhibited, by, caffeine, 'and/or', 'A1R', antagonists, in, preclinical, studies])]). relacion([sujeto(['All', adenosine, receptors]), verbo([have]), complemento([effects, on, spinal, glial, cells, in, regulating, 'nociception,', and, gender, differences, in, the, involvement, of, such, cells, in, chronic, neuropathic, pain, indicate, gender, may, also, need, attention, in, preclinical, and, human, trials, evaluating, the, efficacy, of, 'adenosine-based', analgesics])]). relacion([sujeto(['A', 'fullerene-based', photosensitizer, is, incorporated, postsynthetically, into, a, 'Zr6', -, based, 'MOF,', 'NU-1000,', for]), verbo([enhanced]), complemento([singlet, oxygen, production])]). relacion([sujeto(['The', structural, organic, linkers, in, the, 'MOF', platform, also]), verbo([act]), complemento([as, photosensitizers, which, contribute, to, the, overall, generation, of, singlet, oxygen, from, the, material, under, 'UV', irradiation])]). relacion([sujeto(['Previous', studies, in, the, action, observation, literature]), verbo([have]), complemento([largely, ignored, this, 'ubiquitous,', if, often, 'unwanted,', characteristic, of, motor, 'performance,', assuming, movement, patterns, to, be, highly, similar, across, repetitions, and, individuals])]). relacion([sujeto(['We']), verbo([found]), complemento([that, motor, styles, directly, influenced, 'observers\'', ability, to, '\'', 'read\'', 'others\'', 'intention,', with, some, styles, always, being, less, '\'', 'readable\'', than, others])]). relacion([sujeto(['These', results]), verbo([provide]), complemento([experimental, support, for, the, significance, of, motor, variability, for, action, 'prediction,', suggesting, that, the, ability, to, predict, what, another, person, is, likely, to, do, next, directly, depends, on, her, individual, movement, style])]). relacion([sujeto(['Within', this, 'framework,', the, spatial, distribution, of, fuel, breaks, is, reduced, to, the, problem, of]), verbo([finding]), complemento([network, nodes, '(', small, land, 'patches)', which, favour, fire, propagation])]). relacion([sujeto(['Interestingly,', our, approach]), verbo([reveals]), complemento([that, patches, with, sparse, density, of, vegetation, may, act, as, hubs, for, the, spread, of, the, fire])]). relacion([sujeto(['Due', to, the, limited, coding, capacity, of, their, 'RNA', 'genomes,', 'EV71', and, other, picornaviruses, typically]), verbo([recruit]), complemento([host, 'factors,', known, as, 'IRES', 'trans-acting', factors, '(', 'ITAFs),', to, mediate, 'IRES-dependent', translation])]). relacion([sujeto(['Here,', we, show, that, 'EV71', viral, proteinase, 2, 'A', is, capable, of, cleaving, far, upstream, 'element-binding', protein, 1, '(', 'FBP1),', a, positive, 'ITAF', that, directly]), verbo([binds]), complemento([to, the, 'EV71', 5, '\'', 'UTR', linker, region, to, promote, viral, 'IRES-driven', translation])]). relacion([sujeto(['Interestingly,', the, cleavage, product]), verbo([acts]), complemento([to, promote, viral, 'IRES', activity])]). relacion([sujeto(['Footprinting', analysis, and, gel, mobility, shift, assay, results, showed, that, 'FBP11-371', similarly]), verbo([binds]), complemento([to, the, 'EV71', 5, '\'', 'UTR', linker, 'region,', but, at, a, different, site, from, 'full-length', 'FBP1;', 'moreover,', 'FBP1', and, 'FBP11-371', were, found, to, act, additively, to, promote, 'IRES-mediated', translation, and, virus, yield])]). relacion([sujeto(['Our', findings, expand, the, current, understanding, of, 'virus-host', interactions, with, regard, to, viral, recruitment, and, modulation, of, 'ITAFs,', and]), verbo([provide]), complemento([new, insights, into, translational, control, during, viral, infection])]). relacion([sujeto(['There,', the, viral, glycoprotein, hemagglutinin, '(', 'HA)']), verbo([triggers]), complemento([fusion, between, endosomal, and, viral, 'membrane,', a, critical, step, that, leads, to, release, of, the, viral, segmented, genome, destined, to, reach, the, cell, nucleus])]). relacion([sujeto(['Endosomal', maturation, is, a, complex, process]), verbo([involving]), complemento([acidification, of, the, endosomal, lumen, as, well, as, endosome, motility, along, microtubules])]). relacion([sujeto(['We', identified, the, time, point, of, 'virus-endosome', fusion, and, thereby, the, diffusion, distance, of, the]), verbo([released]), complemento([viral, genome, to, the, nucleus, as, a, critical, bottleneck, for, efficient, virus, infection])]). relacion([sujeto(['In', the, 'brain,', the, striatum, and, prefrontal, cortex]), verbo([interact]), complemento([to, gauge, the, value, of, actions, and, the, 'self-regulatory', demands, in, a, given, environment])]). relacion([sujeto(['New', 'research,']), verbo([involving]), complemento([manipulation, of, the, neural, 'circuitry,', has, revealed, multiple, routes, by, which, '\'', 'imbalances\'', in, circuit, function, cause, regulation, deficits])]). relacion([sujeto(['Novel', 'protein interactions']), verbo([suggest]), complemento([a, highly, complicated, process, rather, than, the, simple, removal, of, unnecessary, genes])]). relacion([sujeto(['This', includes, the, '\'', direct, 'pathway\'', with, striatal, projection, neurons, '(', 'SPNs)']), verbo([expressing]), complemento([dopamine, 'D1', 'receptors,', which, act, to, inhibit, the, tonically, active, 'GABAergic', output, neurons, in, globus, pallidus, interna, and, substantia, nigra, pars, reticulata, that, at, rest, keep, the, brainstem, motor, centres, under, tonic, inhibition])]). relacion([sujeto(['The', net, effect, of, the, direct, pathway, is, to, disinhibit, brainstem, motor, centres, and]), verbo([release]), complemento([motor, 'programs,', while, the, indirect, pathway, instead, will, suppress, motor, activity])]). relacion([sujeto(['We', predict, that, the, basal, ganglia, contains, a, series, of, modules, each, controlling, a, given, pattern, of, behaviour, including, 'locomotion,', 'eye-movements,', 'posture,', and, chewing, that, contain, both, the, direct, pathway, to]), verbo([release]), complemento([a, motor, program, and, the, indirect, pathway, to, inhibit, competing, behaviours])]). relacion([sujeto(['During', vertebrate, evolution, with, a, progressively, more, diverse, motor, 'behaviour,', the, number, of, modules, 'will have']), verbo([increased]), complemento([progressively])]). relacion([sujeto(['The', 'Americans', with, 'Disabilities', 'Act', prohibits, discrimination, on, the, basis, of, disability, and]), verbo([requires]), complemento([schools, to, provide, reasonable, accommodations, for, persons, with, disabilities])]). relacion([sujeto(['Indeed,', 'Ly6C+', monocytes, and, their, descendants]), verbo([have]), complemento([emerged, as, a, 'third,', highly, plastic, and, dynamic, cellular, system, that, complements, the, two, 'classical,', 'tissue-resident', mononuclear, phagocyte, 'compartments,', i])]). relacion([sujeto(['Following', recruitment, to, injured, 'tissue,', 'Ly6C+', monocytes]), verbo([respond]), complemento([to, local, cues, and, can, critically, contribute, to, the, initiation, and, resolution, of, inflammatory, reactions])]). relacion([sujeto(['The', second, main, murine, monocyte, 'subset,', 'Ly6C-', 'cells,', derive, in, steady, state, from, 'Ly6C+', monocytes, and, remain, in, the, 'vasculature,', where, the, cells]), verbo([act]), complemento([as, scavengers])]). relacion([sujeto(['Given', the, central, role, of, monocytes, in, homeostasis, and, 'pathology,', 'in-depth', study, of, this, cellular, compartment, can, be, highly, informative, on, the, health, state, of, the, organism, and]), verbo([provides]), complemento([an, attractive, target, for, therapeutic, intervention])]). relacion([sujeto(['Triglycerides', '(', 'TGs)', are, among, the, most, efficacious, stimulators, of, incretin, 'secretion;', 'however,', the, relative, importance, of, 'FFA1', '(', 'G', 'Protein-coupled', 'Receptor', '[', 'GPR]', 40, ')', ',', 'FFA4', '(', 'GPR120),', and, 'GPR119,', which, all]), verbo([recognize]), complemento(['TG', 'metabolites,', 'ie,', 'long-chain', fatty, acid, and, 2, -, 'monoacylglycerol,', 'respectively,', is, still, unclear])]). relacion([sujeto(['Here,', we]), verbo([find]), complemento([all, 3, receptors, to, be, highly, expressed, and, highly, enriched, in, 'fluorescence-activated', cell, 'sorting-purified', 'GLP-1', and, 'GIP', cells, isolated, from, transgenic, reporter, mice])]). relacion([sujeto(['In', 'vivo,', the, 'TG-induced']), verbo([increase]), complemento([in, plasma, 'GIP', was, significantly, reduced, in, 'FFA1-deficient', mice, '(', to, 34, '%', ',', mean, of, 4, experiments, each, with, 8, -, 10, 'animals),', in, 'GPR119-deficient', mice, '(', to, 24, '%', ')', and, in, 'FFA1/FFA4', double, deficient, mice, '(', to, 15, '%', ')', but, not, in, 'FFA4-deficient', mice])]). relacion([sujeto(['The', 'TG-induced']), verbo([increase]), complemento([in, plasma, 'GLP-1', was, only, significantly, reduced, in, the, 'GPR119-deficient', and, the, 'FFA1/FFA4', double, deficient, 'mice,', but, not, in, the, 'FFA1,', and, 'FFA4-deficient', mice])]). relacion([sujeto(['In', mouse, colonic, crypt, cultures, the, synthetic, 'FFA1', 'agonists,', 'TAK-875']), verbo([stimulated]), complemento(['GLP-1', secretion, to, a, similar, extent, as, the, prototype, 'GLP-1', secretagogue, neuromedin, 'C;', 'this,', 'however,', only, corresponded, to, approximately, half, the, maximal, efficiency, of, the, 'GPR119', agonist, 'AR231453,', whereas, the, 'GPR120', agonist, 'Metabolex-209', had, no, effect])]). relacion([sujeto(['It', is, concluded, that, the, 2, -, monoacylglycerol, receptor, 'GPR119', is, at, least, as, important, as, the, 'long-chain', fatty, acid, receptor, 'FFA1', in]), verbo([mediating]), complemento([the, 'TG-induced', secretion, of, incretins, and, that, the, 2, receptors, act, in, 'synergy,', whereas, 'FFA4', plays, a, minor, if, any, role])]). relacion([sujeto(['Simultaneously', acquired, and, registered, 'FDG-PET/DWI', allowed, quantifiable, descriptions, of, breast, cancer, microenvironments, that, may]), verbo([provide]), complemento([a, framework, for, monitoring, and, predicting, response, to, treatment])]). relacion([sujeto(['Cardiomyopathy', and]), verbo([associated]), complemento([heart, failure, continues, to, be, one, of, the, most, severe, complications, that, threaten, a, large, population])]). relacion([sujeto(['Norepinephrine', '(', 'NE),', a, catecholamine, and, also, a, stress, hormone, may]), verbo([cause]), complemento([the, cardiomyocytes, to, develop, increased, sensitivity, to, death, with, its, increasing, concentrations])]). relacion([sujeto(['The', aim, of, the, study, was, to, assess, the, effect, of, curcumin, in]), verbo([preventing]), complemento([the, occurrence, of, features, underlying, apoptosis, such, as, nuclear, 'disruption,', chromatin, 'condensation,', 'DNA', fragmentation, and, alterations, in, mitochondrial, membrane, permeability])]). relacion([sujeto(['Hence,', we, propose, that, curcumin]), verbo([has]), complemento([the, potential, to, act, as, a, therapeutic, agent, for, the, attenuation, of, 'NE-induced', cardiac, cell, death, and, modulation, of, apoptosis, in, 'H9c2', cardiomyocytes])]). relacion([sujeto(['Simvastatin', '(', 'SIM),', a, 3, -, 'hydroxy-3-methylglutaryl', 'coenzyme A', reductase, 'inhibitor,']), verbo([has]), complemento([been, reported, to, inhibit, the, activity, of, 'hepatitis B', virus, '(', 'HBV),', 'however,', the, mechanism, underlying, its, antiviral, function, remains, unknown])]). relacion([sujeto(['Minichromosome', maintenance, '(', 'MCM) 7,', a, component, of, the, 'MCM', 'complex,']), verbo([has]), complemento([been, reported, to, act, as, an, important, host, factor, aiding, virus, genome, replication, in, host, cells])]). relacion([sujeto(['The', present, study, demonstrated, that, downregulation, of, 'MCM7']), verbo([inhibited]), complemento([the, expression, of, proteins, transferred, by, adenoviral, vectors])]). relacion([sujeto(['This']), verbo([suggests]), complemento([an, association, between, 'MCM7', and, viral, 'DNA', expression])]). relacion([sujeto(['Western', blot, experiments, indicated, that, 'SIM', improved, the, activation, of, eukaryotic, initiation, 'factor‑2α', '(', 'eIF2α),', a, protein, synthesis, initiation, 'factor,', and, upregulated, the, upstream, factors, of, 'eIF2α,', protein, kinase, 'RNA‑like', endoplasmic, reticulum, 'kinase,', which, is]), verbo([regulated]), complemento([by, the, liver, 'kinase B1', '(', 'LKB1)‑AMP‑activated', protein, kinase, '(', 'AMPK)', signaling, pathway])]). relacion([sujeto(['These', results, indicated, that, 'SIM']), verbo([induced]), complemento(['HBV', downregulation, via, an, 'MCM‑dependent', 'mechanism,', and, 'SIM', may, inhibit, 'MCM7', expression, by, increasing, the, phosphorylation, of, 'eIF2α,', which, is, mediated, by, the, 'LKB1-AMPK', signaling, pathway])]). relacion([sujeto(['The', 'Forkhead', 'box O', '(', 'FOXO)', protein, family, is, predominantly]), verbo([involved]), complemento([in, 'apoptosis,', oxidative, 'stress,', 'DNA', 'damage/repair,', tumor, 'angiogenesis,', 'glycometabolism,', regulating, life, span, and, other, important, biological, processes])]). relacion([sujeto(['When', cells, are, subjected, to, different, 'environments,', the, corresponding, 'PTMs']), verbo([act]), complemento([on, the, 'FOXO', protein, 'family,', to, change, transcriptional, activity, or, subcellular, 'localization,', and, the, expression, of, downstream, target, 'genes,', will, ultimately, affect, the, biological, behavior, of, the, cells])]). relacion([sujeto(['MicroRNAs', '(', 'miRNAs)', were]), verbo([reported]), complemento([to, be, involved, in, the, development, of, clear, cell, renal, cell, carcinoma, '(', 'ccRCC)'])]). relacion([sujeto(['The', present, study, identified, miRNAs, which, could]), verbo([act]), complemento([as, potential, novel, prognostic, markers, for, 'ccRCC,', and, analyzed, its, possible, mechanism])]). relacion([sujeto(['We']), verbo([found]), complemento([that, 'miR-19a', correlated, with, poor, prognosis, of, ccRCC, patients, via, promoting, cell, proliferation, and, suppressing, 'PTEN/SMAD4', expression])]). relacion([sujeto(['Both', the, microarray, screening, result, and, 'TCGA', 'KIRC', dataset, analysis, showed, that, 'miR-19a', was, significantly, upregulated, in, ccRCC, 'tissues,', and, further, analysis, of, 'TCGA', data, revealed, that, the, upregulated, level, of, 'miR-19a', was, strongly]), verbo([associated]), complemento([with, advanced, 'T', stage, and, poor, prognosis, of, ccRCC, patients])]). relacion([sujeto(['Consistent', with, clinical, 'observations,', 'miR-19a', overexpression, significantly]), verbo([promoted]), complemento([ccRCC, cell, proliferation, 'in vitro'])]). relacion([sujeto(['To', further, explore, the, mechanism, by, which, 'miR-19a', correlated, with, cell, proliferation, and, poor, prognosis, of, 'ccRCC,', we, performed, gene, set, enrichment, analysis, '(', 'GSEA)', for]), verbo([target]), complemento([genes, of, 'miR-19a', in, ccRCC, patients])]). relacion([sujeto(['Result', indicated, that, the, key]), verbo([target]), complemento([genes, of, 'miR-19a', included, 'SMAD4', and, 'PTEN'])]). relacion([sujeto(['In', ccRCC, 'tissues,', expression, levels, of, 'SMAD4', and, 'PTEN', were, negatively, correlated, with, expression, level, of, 'miR-19a,']), verbo([revealed]), complemento([that, 'miR-19a', suppressed, the, expression, of, 'SMAD4', and, 'PTEN', in, ccRCC, patients])]). relacion([sujeto(['miR-19a', overexpression, significantly]), verbo([suppressed]), complemento([the, expression, of, 'SMAD4', and, 'PTEN', 'in vitro,', further, verifying, that, 'SMAD4', and, 'PTEN', were, the, target, genes, of, 'miR-19a', in, ccRCC, cells])]). relacion([sujeto(['Our', results, elucidated, the, tumor]), verbo([promoting]), complemento([role, of, 'miR-19a', and, established, 'miR-19a', as, a, potential, novel, prognostic, marker, for, ccRCC])]). relacion([sujeto(['Veno-venous', 'extra-corporeal', membrane, oxygenation, '(', 'vv-ECMO)', is, an, established, salvage, therapy, for, severe, respiratory, 'failure,', and, may]), verbo([provide]), complemento([an, alternative, form, of, treatment, for, 'trauma-induced', acute, respiratory, distress, syndrome, '(', 'ARDS)', when, conventional, treatments, have, failed])]). relacion([sujeto(['In', all, documented, cases, of, bleeding, a, bolus, and, infusion, of, heparin, was, 'administered,', aiming, for, an, 'ACT']), verbo([target]), complemento([&, 'gt;', 150, s])]). relacion([sujeto(['Our', experience, and, our, literature, review]), verbo([suggests]), complemento([that, 'vv-ECMO', should, be, considered, as, rescue, treatment, for, the, management, of, severe, hypoxemic, respiratory, failure, secondary, to, 'ARDS', in, trauma, patients])]). relacion([sujeto(['In', patients, with, a, moderate, risk, of, 'bleeding,', use, of, a, heparin, infusion, keeping, an, 'ACT']), verbo([target]), complemento([&, 'lt;', 150, s, can, be, appropriate])]). relacion([sujeto(['Endomorphins']), verbo([interact]), complemento([selectively, with, the, 'μ-opioid', or, 'MOP', receptors, and, exhibit, nanomolar, or, 'sub-nanomolar', receptor, binding, 'affinities,', therefore, they, suggested, to, be, endogenous, agonists, for, the, 'μ-opioid', receptors])]). relacion([sujeto(['Endomorphins']), verbo([mediate]), complemento([a, number, of, characteristic, opioid, 'effects,', such, as, 'antinociception,', however, there, are, several, physiological, functions, in, which, endomorphins, appear, to, act, in, a, fashion, that, does, not, involve, binding, to, and, activation, of, the, 'μ-opioid', receptor])]). relacion([sujeto(['Our', recent, data, indicate, that, a, radiolabelled, '[', '(', 3, ')', 'H]endomorphin-1', with, a, specific, radioactivity, of, 2.35, 'TBq/mmol', -, prepared, by, catalytic, dehalogenation, of, the, diiodinated, peptide, precursor, in, the, presence, of, tritium, gas, -, is, able, to]), verbo([bind]), complemento([to, a, 'second,', naloxone, insensitive, recognition, site, in, rat, brain, membranes])]). relacion([sujeto([',', the, presence, of, higher, '(', 'Kd', =, 0.4, nM, /, 'Bmax', =, 120, 'fmol/mg', 'protein)', and, lower, '(', 'Kd', =, 8.2, nM, /, 'Bmax', =, 432, 'fmol/mg', 'protein)', affinity]), verbo([binding]), complemento([components, is, observed, both, in, saturation, binding, experiments, followed, by, 'Schatchard', 'analysis,', and, in, equilibrium, competition, binding, studies])]). relacion([sujeto([',', curvilinear, 'Schatchard', plots, or, biphasic, displacement, curves, are, seen, only, if, the, 'non-specific']), verbo([binding]), complemento([is, measured, in, the, presence, of, excess, unlabeled, 'endomorphin-1', and, not, in, the, presence, of, excess, unlabeled, naloxone])]). relacion([sujeto(['The', 'second,', lower, affinity, 'non-opioid']), verbo([binding]), complemento([site, is, not, recognized, by, heterocyclic, opioid, alkaloid, 'ligands,', neither, agonists, such, as, 'morphine,', nor, antagonists, such, as, naloxone])]). relacion([sujeto(['On', the, 'contrary,', 'endomorphin-1', is, displaced, from, its, lower, 'affinity,', higher, capacity]), verbo([binding]), complemento([site, by, several, natural, 'neuropeptides,', including, 'methionine-enkephalin-Arg-Phe,', 'nociceptin-orphanin', 'FQ,', angiotensin, and, 'FMRF-amide'])]). relacion([sujeto(['This', 'naloxone-insensitive,', consequently, 'non-opioid']), verbo([binding]), complemento([site, seems, to, be, present, in, nervous, tissues, carrying, low, density, or, no, 'μ-opioid', 'receptors,', such, as, rodent, 'cerebellum,', or, brain, of, 'μ-opioid', receptor, deficient, '(', 'MOPr(-/-))', transgenic, or, '\'', 'knock-out\'', '(', 'K'])]). relacion([sujeto(['The', newly, described, 'non-opioid']), verbo([binding]), complemento([component, is, not, coupled, to, regulatory, 'G-proteins,', nor, does, it, affect, adenylyl, cyclase, enzyme, activity])]). relacion([sujeto(['Dioxiranes', are, powerful, oxidants, that, can]), verbo([act]), complemento([via, two, different, 'mechanisms:', 1, ')', homolytic, '(', 'H', abstraction, and, oxygen, 'rebound)', and, 2, ')', heterolytic, '(', electrophilic, 'oxidation)'])]). relacion([sujeto(['So', 'far,', it]), verbo([has]), complemento([been, reported, that, the, nature, of, the, substrate, dictates, the, reaction, mode, independently, from, the, dioxirane, employed])]). relacion([sujeto(['Herein,', we]), verbo([report]), complemento([an, unprecedented, case, in, which, the, nature, of, the, dioxirane, rules, the, oxidation, chemoselectivity])]). relacion([sujeto(['Low', support, was]), verbo([associated]), complemento([with, poor, work, ability, for, both, women, and, men, '(', 'OR', 1.78, and, 1.89, ')'])]). relacion([sujeto(['For', 'men,', also, low, skill, discretion, was]), verbo([associated]), complemento([with, poor, work, ability, '(', 'OR', 2.07, ')'])]). relacion([sujeto(['For', both, women, and, 'men,', 'PD', was]), verbo([associated]), complemento([with, poor, work, ability, '(', 'OR', 3.41, and, 1.84, ')'])]). relacion([sujeto(['PD', did, not]), verbo([act]), complemento([as, an, intermediate, variablein, the, association, between, 'PWF', and, work, ability])]). relacion([sujeto(['Compared', with, the, contralateral, 'controls,']), verbo([decreased]), complemento([expression, of, 'OPG', and, 'BMP-2', at, 3, days, after, roughly, focused, 'ESWT,', followed, by, a, later, increase, at, 7, 'days,', was, indicated, by, 'real-time', 'PCR', and, 'Western', blotting, analysis])]). relacion([sujeto(['The', 'OPG', messenger, 'RNA', '(', 'mRNA)', expression, levels, peaked, at, 6, weeks, after, the, shock, wave, 'treatment,', paired, with, a, much, earlier, '(', at, 4, 'weeks)']), verbo([increase]), complemento([of, 'BMP-2,', and, declined, close, to, normal, at, 8, weeks])]). relacion([sujeto(['Roughly', focused, 'ESWT', may]), verbo([promote]), complemento([the, expression, of, 'OPG', and, 'BMP-2', in, the, osteoporotic, fracture, area, in, rats])]). relacion([sujeto(['BMP-2', and, 'OPG', may]), verbo([act]), complemento([synergistically, and, may, lead, to, a, significant, enhancement, of, bone, formation, and, remodeling])]). relacion([sujeto(['The', effects, of, 'A,', 'B', and, 'C', individually, and, their, combinations, were, investigated, using, proton]), verbo([nuclear]), complemento([magnetic, resonance, '(', 1, 'H', 'NMR)-based', metabolomics, complemented, with, neurologic, deficit, 'scoring,', infarct, volume, 'measurement,', 'biochemistry,', histopathology, and, 'immunohistochemistry,', as, well, as, quantitative, 'real-time', polymerase, chain, reaction, '(', 'qRT-PCR)', and, western, blotting])]). relacion([sujeto(['Ischemic', stroke, produces, severe, oxidative, 'stress,', which]), verbo([induces]), complemento([further, damage])]). relacion([sujeto(['Our', results, show, that, the, 'ABC', combination, treatment]), verbo([increased]), complemento([levels, of, cellular, antioxidants, that, scavenged, reactive, oxygen, species, during, 'ischemia-reperfusion', via, the, nuclear, erythroid, 2, -, related, factor, 2, '(', 'Nrf2)', signaling, cascade])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, a, combination, of, component, herbs, in, 'HLJDD', exhibit, stronger, effects, than, the, individual, herbs, alone])]). relacion([sujeto(['Our', integrated, metabolomics, approach, also]), verbo([provides]), complemento([a, 'tractable,', powerful, tool, for, understanding, the, science, behind, 'TCM', formulations])]). relacion([sujeto(['To', set, up, an, operational, basis, of, the, 'Realizing', the, 'European', 'Network', of, 'Biodosimetry', '(', 'RENEB)', network, within, which, the, application, of, seven, established, biodosimetric, tools, '(', the, dicentric, 'assay,', the, 'FISH', 'assay,', the, micronucleus, 'assay,', the, 'PCC', 'assay,', the, 'gamma-H2AX', 'assay,', electron, paramagnetic, resonance, and, optically]), verbo([stimulated]), complemento(['luminescence)', will, be, compared, and, standardized, among, the, participating, laboratories])]). relacion([sujeto(['Two', intercomparisons, were, organized, where, blood, samples, and, smartphone, components, were, 'irradiated,', coded, and, sent, out, to]), verbo([participating]), complemento([laboratories, for, dosimetric, analysis])]). relacion([sujeto(['Moreover,', an, accident, exercise, was, organized, during, which, each, 'RENEB', partner, had, the, chance, to, practice, the, procedure, of]), verbo([activating]), complemento([the, network, and, to, handle, large, amounts, of, dosimetric, results])]). relacion([sujeto(['Overall,', the, precision, of, dose, estimates, improved, between, intercomparisons, 1, and, 2, ',', clearly, showing, the, value, of, running, such]), verbo([regular]), complemento([activities])]). relacion([sujeto(['The', 'RENEB', network, is, fully, operational, and, ready, to]), verbo([act]), complemento([in, case, of, a, major, radiation, emergency])]). relacion([sujeto(['Twenty-eight', male, inmates]), verbo([participated]), complemento([in, qualitative, interviews, across, three, correctional, centres, in, 'New', 'South', 'Wales,', 'Australia'])]). relacion([sujeto(['Although', linking, social, capital, between, inmates, and, nurses, appeared, influential, in, 'HCV', treatment, 'access,', there, remained, opportunities, for]), verbo([increasing]), complemento([linking, social, capital, within, the, prison, setting, '(', such, as, 'nurse-led', engagement, within, the, 'prisons)'])]). relacion([sujeto(['Bonding', and, linking, social, capital, can, be, valuable, resources, in]), verbo([promoting]), complemento(['HCV', treatment, 'awareness,', uptake, and, adherence])]). relacion([sujeto(['Peer-based', programmes, are, likely, to, be, influential, in]), verbo([promoting]), complemento(['HCV', outcomes, in, the, prison, setting])]). relacion([sujeto(['Engagement', in, 'prisons,', outside, of, the, 'clinics,', would]), verbo([enhance]), complemento([opportunities, for, linking, social, capital, to, influence, 'HCV', treatment, outcomes])]). relacion([sujeto(['Antibiotic', resistance]), verbo([has]), complemento([emerged, as, a, major, threat, to, global, health, care])]). relacion([sujeto(['This', is, largely, due, to, the, fact, that, many, pathogens]), verbo([have]), complemento([developed, strategies, to, acquire, resistance, to, antibiotics])]). relacion([sujeto(['Metallo-β-lactamases', '(', 'MBL)']), verbo([have]), complemento([evolved, to, inactivate, most, of, the, commonly, used, 'β-lactam', antibiotics])]). relacion([sujeto(['Unlike', other, 'MBLs', it, appears, that, 'AIM-1']), verbo([has]), complemento([two, avenues, available, for, the, turnover, of, the, substrate, 'nitrocefin,', distinguished, by, the, identity, of, the, 'rate-limiting', step])]). relacion([sujeto([melazonatus, and, 'Iguanodectes', 'geisleri)']), verbo([found]), complemento([under, different, 'co-occurrence', circumstances, in, 'Amazonian', upland, streams])]). relacion([sujeto(['The', opportunistic, habits, and, great, feeding, flexibility, of, these, characid, species, make, the, partitioning, of, food, resources, possible, and]), verbo([act]), complemento([as, an, important, ecological, mechanism, that, facilitates, the, coexistence, of, different, 'species,', possibly, by, attenuating, the, effects, of, direct, competition, for, food])]). relacion([sujeto(['On', 4, 'August', 2011, 'a modification', of, the, infection, protection]), verbo([act]), complemento([became, 'law,', meaning, that, antibiotic, consumption, surveillance, and, evaluation, of, data, on, the, local, resistance, situation, became, obligatory, for, hospitals])]). relacion([sujeto(['Four', years, after, the, modification, of, the, infection, protection]), verbo([act]), complemento([became, 'law,', the, 'Munich', public, health, department, aimed, to, evaluate, the, state, of, implementation, of, antibiotic, consumption, surveillance, in, 'Munich', hospitals, and, to, ascertain, which, antibiotic, stewardship, '(', 'ABS)', structures, have, already, been, established])]). relacion([sujeto(['Only', 32, '%', of, the, hospitals]), verbo([have]), complemento([qualified, 'ABS-experts', available])]). relacion([sujeto(['In', 76, '%', of, the, hospitals, persons, responsible, for, antibiotic, consumption, surveillance, are, 'appointed,', while, in, 12, '%', persons, responsible, for, antibiotic, consumption, surveillance, are, at, least, partly]), verbo([released]), complemento([from, their, normal, work, for, this, activity])]). relacion([sujeto(['For', the, first, time, data, were, collected, on, implementation, of, antibiotic, consumption, surveillance, in, 'hospitals,', which]), verbo([has]), complemento([been, required, by, law, since, 2011])]). relacion([sujeto(['It', was]), verbo([found]), complemento([that, structural, and, personnel, prerequisites, are, often, 'missing,', that, release, from, normal, work, for, this, additional, duty, is, rarely, granted, and, that, the, evaluation, of, data, is, often, either, missing, or, does, not, correspond, to, the, legal, requirements, by, omitting, to, take, account, of, the, local, resistance, situation])]). relacion([sujeto(['Optimized', dosage, regimens, of, antibiotics]), verbo([have]), complemento([remained, obscure, since, their, introduction])]). relacion([sujeto(['During', the, last, two, decades, 'pharmacokinetic(PK)-pharmacodynamic(PD)', 'relationships,', originally, established, in, animal, 'experiments,']), verbo([have]), complemento([been, increasingly, used, in, patients])]). relacion([sujeto(['Aminoglycosides']), verbo([act]), complemento([as, planned, when, the, peak, concentration, is, 'a multiple', of, the, 'MIC', and, vancomycin, seems, to, work, best, when, the, area, under, the, plasma, vs])]). relacion([sujeto([time, curve, '(', 'AUC)', to, 'MIC']), verbo([has]), complemento(['a certain', ratio])]). relacion([sujeto(['In', times, where, all, antibiotics, can, be, measured, with, new, 'technologies,', the, introduction, of, therapeutic, drug, monitoring, '(', 'TDM)', is]), verbo([suggested]), complemento([for, 'ICUs', '(', 'Intensive', 'Care', 'Unit)'])]). relacion([sujeto(['Because', the, workers, believed, the]), verbo([cause]), complemento([of, the, mental, disorders, was, 'work-related', stress, or, a, specific, 'event,', we, could, identify, the, major, 'work-related', stressor, for, claimed, cases])]). relacion([sujeto(['We', included, claimed, cases, of, occupational, mental, disorder, or, suicide]), verbo([reported]), complemento([during, 2010, -, 2014, to, the, 'Korea', 'Workers', 'Compensation', and, 'Welfare', 'Service', '(', 'KCOMWEL),', established, by, 'Industrial', 'Accidents', 'Insurance', '(', 'IACI)', 'Act'])]). relacion([sujeto(['Of', the, 569, claimed, 'cases,', 142, cases, were]), verbo([recognized]), complemento([as, occupational, mental, disorder, or, suicide])]). relacion([sujeto(['Claims', due, to, mental, disorders, or, suicide]), verbo([increased]), complemento([during, the, 5, -, year, study, 'period,', and, the, approval, rate, was, approximately, 33, &, 'nbsp;%,', and, the, main, stressor, of, the, claimed, cases, was, an, acute, stressful, event, such, as, physiologic, 'trauma,', 'employment-related', 'issues,', fear, of, legal, or, financial, 'responsibility,', abrupt, change, in, organizational, 'responsibility,', or, workplace, violence])]). relacion([sujeto(['It', is, understood, in, broad, terms, that, to, survive, waterbirds, must, move, according, to, phases, of, 'wet-dry', 'cycles,', with, coastal, habitats]), verbo([providing]), complemento([drought, refugia, and, inland, wetlands, used, during, the, wet, phase])]). relacion([sujeto(['However,', both, inland, and, coastal, wetlands, are, subject, to, major, anthropogenic, 'pressures,', and, the, various, species, of, waterbird, may]), verbo([have]), complemento([particular, habitat, requirements, and, respond, individualistically, to, spatiotemporal, variations, in, resource, distribution])]). relacion([sujeto(['A', better, understanding, of, the, relationships, between, occurrence, of, waterbirds, and, habitat, condition, under, changing, climatic, conditions, and, anthropogenic, pressures, will, help, clarify, patterns, of, habitat, use, and, the]), verbo([targeting]), complemento([of, investments, in, conservation])]). relacion([sujeto(['We']), verbo([provide]), complemento([the, first, predictive, models, of, habitat, availability, between, wet, and, dry, phases, for, six, widely, distributed, waterbird, species, at, a, large, spatial, scale])]). relacion([sujeto(['There', were, large]), verbo([increases]), complemento([in, area, of, suitable, habitat, in, inland, regions, in, the, wet, year, compared, with, the, dry, year, for, all, 'species,', ranging, from, 4.14, '%', for, 'Australian', 'White', 'Ibis', to, 31.73, '%', for, 'Eurasian', 'Coot'])]). relacion([sujeto(['With', over, half, of, the, suitable, habitat, for, three, of, the, six, species, was, located, in, coastal, zones, during, 'drought,', our, study, highlights, the, need, to, identify, and]), verbo([conserve]), complemento([coastal, drought, refuges])]). relacion([sujeto(['Recent', empirical, and, conceptual, papers]), verbo([have]), complemento([highlighted, the, potential, for, metabolism, to, act, as, a, proximate, mechanism, for, behavior, that, could, explain, animal, personality, '(', consistency, over, 'time)'])]). relacion([sujeto(['Under', this, 'hypothesis,', individuals, with, consistently, high, levels, of, behavioral, activity, should, also]), verbo([have]), complemento([high, resting, metabolic, rate, '(', 'RMR)', as, it, can, reflect, capacity, to, process, food, and, generate, energy])]). relacion([sujeto(['RMR', declined, over, time]), verbo([suggesting]), complemento([habituation, to, the, 'protocol,', whereas, peak, metabolism, did, not])]). relacion([sujeto(['We', conclude, that, 'RMR', does, not]), verbo([provide]), complemento([a, proximate, explanation, for, consistent, individual, differences, in, behavior, in, male, 'guppies,', and, therefore, the, potential, for, independent, evolution, of, these, physiological, and, behavioral, traits, seems, possible])]). relacion([sujeto(['Previously,', we, showed, that, iron, can]), verbo([act]), complemento([as, a, 'co-catalyst', to, improve, the, deconstruction, of, lignocellulosic, biomass])]). relacion([sujeto(['However,', directly, adding, iron, catalysts, into, biomass, prior, to, pretreatment, is, diffusion, 'limited,', and]), verbo([increases]), complemento([the, cost, of, biorefinery, operations])]). relacion([sujeto(['Recently,', we, developed, a, new, strategy, for]), verbo([expressing]), complemento(['iron-storage', protein, ferritin, intracellularly, to, accumulate, iron, as, a, catalyst, for, the, downstream, deconstruction, of, lignocellulosic, biomass])]). relacion([sujeto([accumulated, iron, under, both, normal, and, 'iron-fertilized', growth, 'conditions;', under, the, latter, '(', 'iron-fertilized)', 'condition,', 'FerEX', transgenic, plants, showed, an]), verbo([increase]), complemento([in, plant, height, and, dry, weight, by, 12, and, 18, &, 'nbsp;%,', 'respectively,', compared, with, the, empty, vector, control, plants])]). relacion([sujeto(['Remarkably,', their, harvested, biomasses, showed]), verbo([enhanced]), complemento([pretreatability, and, 'digestibility,', 'releasing,', 'respectively,', 21, &, 'nbsp;%', more, glucose, and, 34, &, 'nbsp;%', more, xylose, than, the, empty, vector, control, plants])]). relacion([sujeto(['These', values, are, significantly, higher, than, those, of, our, recently, obtained, ferritin, intracellularly]), verbo([expressed]), complemento([plants])]). relacion([sujeto(['This', study, demonstrated, that, extracellular, expression, of, ferritin, in, 'Arabidopsis', can, produce, plants, with]), verbo([increased]), complemento([growth, and, iron, 'accumulation,', and, reduced, thermal, and, enzymatic, recalcitrance])]). relacion([sujeto(['We', identified, 44, common, and, rare, functional, variants]), verbo([associated]), complemento([with, mild, to, moderate, 'MDD', in, the, 'Mexican-American', cohort, '(', 'genome-wide', false, discovery, 'rate,', 'FDR,', &, 'lt;0'])]). relacion([sujeto(['Whole-genome', sequencing, analyses, of, a, subset, of, the, cohorts, revealed, that, 'European-ancestry', individuals]), verbo([have]), complemento([a, significantly, reduced, '(', 50, '%', ')', number, of, single, nucleotide, variants, compared, with, 'Mexican-American', 'individuals,', and, for, this, reason, the, role, of, rare, variants, may, vary, across, populations])]). relacion([sujeto(['Furthermore,', using, an, animal, model, of, 'stress,', we]), verbo([found]), complemento([that, 'Phf21b', hippocampal, gene, expression, is, significantly, decreased, in, animals, resilient, to, chronic, restraint, stress, when, compared, with, 'non-chronically', stressed, animals])]). relacion([sujeto(['Together,', our, results]), verbo([reveal]), complemento([that, including, stress, level, data, enables, the, identification, of, novel, rare, functional, variants, associated, with, 'MDD'])]). relacion([sujeto(['Hippocampal', neurogenesis]), verbo([has]), complemento([been, proposed, to, participate, in, a, myriad, of, behavioral, 'responses,', both, in, basal, states, and, in, the, context, of, neuropsychiatric, disorders])]). relacion([sujeto(['Here,', we, identify]), verbo([activating]), complemento([protein, 2, γ, '(', 'AP2γ,', also, known, as, 'Tcfap2c),', originally, described, to, regulate, the, generation, of, neurons, in, the, developing, 'cortex,', as, a, modulator, of, adult, hippocampal, glutamatergic, neurogenesis, in, mice])]). relacion([sujeto(['There,', it, is]), verbo([found]), complemento([to, act, as, a, positive, regulator, of, the, cell, fate, determinants, 'Tbr2', and, 'NeuroD,', promoting, proliferation, and, differentiation, of, new, glutamatergic, granular, neurons])]). relacion([sujeto(['To', estimate, mutation, rates, and, evaluate, the, effect, of, selection, on, new, 'mutations,', we, propagated, mutation, accumulation, '(', 'MA)', lines, of, 'Daphnia', pulex, for, more, than, 82, generations, and]), verbo([maintained]), complemento([a, 'non-MA', population, under, conditions, where, selection, could, act])]). relacion([sujeto(['The', high, overall, rate, of]), verbo([loss]), complemento([of, heterozygosity, '(', 'LOH)', of, 4.82, ×, 10, '(', -, 5, ')', per, site, per, generation, was, due, to, a, large, ameiotic, recombination, event, spanning, an, entire, arm, of, a, chromosome, '(', '~6', 'Mb)', and, several, hemizygous, deletion, events, spanning, '~2', kb, each])]). relacion([sujeto(['In', the, 'non-MA', 'population,', we]), verbo([found]), complemento([significantly, fewer, mutations, than, expected, based, on, the, rate, derived, from, the, 'MA', 'experiment,', indicating, purifying, selection, was, likely, acting, to, remove, new, deleterious, mutations])]). relacion([sujeto(['Our', findings]), verbo([suggest]), complemento([that, both, positive, and, negative, selection, on, new, mutations, is, powerful, and, effective, in, a, strictly, clonal, population])]). relacion([sujeto(['A', novel, class, of, mesoionic, 'pyrido[1,2-a]pyrimidinones']), verbo([has]), complemento([been, discovered, with, exceptional, insecticidal, activity, controlling, a, number, of, insect, 'species,', particularly, hemiptera, and, lepidoptera])]). relacion([sujeto(['Mode-of-action', studies, showed, that, they]), verbo([act]), complemento([on, nicotinic, acetylcholine, receptors, '(', 'nAChRs)', primarily, as, inhibitors])]). relacion([sujeto(['Here', we]), verbo([report]), complemento([the, 'discovery,', 'evolution,', and, preparation, of, this, class, of, chemistry])]). relacion([sujeto(['With']), verbo([increasing]), complemento([evidence, showing, the, involvement, of, oxidative, stress, in, the, pathogenesis, of, various, 'diseases,', the, effects, of, clinical, drugs, possessing, antioxidant, functions, have, received, much, attention])]). relacion([sujeto(['The', unregulated, oxidative, modification, of, biological, molecules]), verbo([leading]), complemento([to, diseases, is, mediated, by, multiple, oxidants, including, free, 'radicals,', 'peroxynitrite,', 'hypochlorite,', 'lipoxygenase,', and, singlet, oxygen])]). relacion([sujeto(['In', the, present, 'study,', the, antioxidant, effects, of, several, clinical, drugs, against, plasma, lipid, oxidation]), verbo([induced]), complemento([by, the, aforementioned, five, kinds, of, oxidants, were, investigated, from, the, production, of, lipid, 'hydroperoxides,', which, have, been, implicated, in, the, pathogenesis, of, various, diseases])]). relacion([sujeto(['Troglitazone']), verbo([acted]), complemento([as, a, potent, peroxyl, radical, 'scavenger,', whereas, probucol, and, edaravone, showed, only, moderate, reactivity, and, 'carvedilol,', 'pentoxifylline,', and, ebselen, did, not, act, as, radical, scavenger])]). relacion([sujeto(['Probucol', and, edaravone]), verbo([suppressed]), complemento([plasma, oxidation, mediated, by, peroxynitrite, and, hypochlorite])]). relacion([sujeto(['Troglitazone', and, edaravone]), verbo([inhibited]), complemento([15, -, lipoxygenase, mediated, plasma, lipid, 'oxidation,', the, 'IC50', being, 20, and, 34, μM, respectively])]). relacion([sujeto(['None', of, the, drugs, used, in, this, study]), verbo([suppressed]), complemento([plasma, lipid, oxidation, by, singlet, oxygen])]). relacion([sujeto(['This', study, shows, that, the, antioxidant, effects, of, drugs, depend, on, the, nature, of, oxidants, and, that, antioxidants, against, multiple, oxidants, are]), verbo([required]), complemento([to, cope, with, oxidative, stress, in, vivo])]). relacion([sujeto(['TP53', is, a, critical, tumor, suppressor, gene, that]), verbo([regulates]), complemento([cell, cycle, 'progression,', 'apoptosis,', cellular, senescence, and, many, other, properties, critical, for, control, of, normal, cellular, growth, and, death])]). relacion([sujeto(['Due', to, the, pleiotropic, effects, that, 'TP53']), verbo([has]), complemento([on, gene, expression, and, cellular, 'physiology,', mutations, at, this, tumor, suppressor, gene, result, in, diverse, physiological, effects])]). relacion([sujeto(['The', expression, of, 'TP53', can, be]), verbo([induced]), complemento([by, various, agents, used, to, treat, cancer, patients, such, as, chemotherapeutic, drugs, and, ionizing, radiation])]). relacion([sujeto(['Radiation', will]), verbo([induce]), complemento(['Ataxia', telangiectasia, mutated, '(', 'ATM)', and, other, kinases, that, results, in, the, phosphorylation, and, activation, of, 'TP53'])]). relacion([sujeto(['TP53', is, also, negatively]), verbo([regulated]), complemento([by, other, 'mechanisms,', such, as, ubiquitination, by, ligases, such, as, 'MDM2'])]). relacion([sujeto(['While', 'TP53']), verbo([has]), complemento([been, documented, to, control, the, expression, of, many, &, 'quot;classical"', genes, '(', e])]). relacion([sujeto([',', 'p21(Cip-1),', 'PUMA,', 'Bax)', by, transcriptional, mechanisms, for, quite, some, 'time,', more, recently, 'TP53']), verbo([has]), complemento([been, shown, to, regulate, microRNA, '(', 'miR)', gene, expression])]). relacion([sujeto(['Different', miRs, can]), verbo([promote]), complemento([oncogenesis, '(', 'oncomiR)', whereas, others, act, to, inhibit, tumor, progression, '(', tumor, suppressor, 'miRs)'])]). relacion([sujeto(['Targeted', therapies, to, stabilize, 'TP53']), verbo([have]), complemento([been, developed, by, various, 'approaches,', 'MDM2/MDM4', inhibitors, have, been, developed, to, stabilize, 'TP53', in, 'TP53-wild', type, '(', 'WT)', tumors])]). relacion([sujeto(['In', 'addition,', small, molecules]), verbo([have]), complemento([been, isolated, that, will, reactivate, certain, mutant, 'TP53s'])]). relacion([sujeto(['Understanding', the, actions, of, 'TP53', may, yield, novel, approaches, to]), verbo([suppress]), complemento(['cancer,', aging, and, other, health, problems])]). relacion([sujeto(['Recognitions', of, signal, molecules, by, 'PRR-ECDs']), verbo([induce]), complemento(['homo-', or, heterooligomerization, of, 'RLKs', and, 'RLPs', to, trigger, corresponding, intracellular, immune, responses])]). relacion([sujeto(['RLKs', possess, a, cytoplasmic, 'Ser/Thr', kinase, domain, that, is, absent, in, 'RLPs,', implying, that, protein, phosphorylations, underlie, key, mechanism, in, transducing, immunity, signalings, and, that, 'RLPs', unlikely]), verbo([mediate]), complemento([signal, transduction, 'independently,', and, recruitment, of, other, 'patterns,', such, as, 'RLKs,', is, required, for, the, function, of, 'RLPs', in, plant, immunity])]). relacion([sujeto(['Receptor-like', cytoplasmic, 'kinases,', resembling, 'RLK', structures, but, lacking, the, 'ECD,']), verbo([act]), complemento([as, immediate, substrates, of, 'PRRs,', modulating, 'PRR', activities, and, linking, 'PRRs', with, downstream, signaling, mediators])]). relacion([sujeto(['In', this, 'chapter,', we, summarize, recent, discoveries, illustrating, the, molecular, machines, of, major, components, of, 'PRR', complexes, in]), verbo([mediating]), complemento([pathogen, perception, and, immunity, activation, in, plants])]). relacion([sujeto(['This', study]), verbo([provides]), complemento([evidence, that, at, low, 'concentrations,', lysine, and, histidine, interact, with, proteins, by, a, combination, of, '(', 1, ')', direct, electrostatic, interactions, with, negatively, charged, side, 'chains,', '(', 2, ')', possible, binding, to, 'high-affinity', hydrophobic, binding, 'sites,', and, '(', 3, ')', 'glycine-mediated', weak, interactions, with, peptide, backbone, and, polar, side, chains])]). relacion([sujeto(['At', high, 'concentrations,', lysine, and, histidine]), verbo([act]), complemento([via, '(', 4, ')', 'glycine-mediated', competition, for, water, between, the, unfolding, protein, and, the, excipient, and, '(', 5, ')', 'sidechain-mediated', interaction, with, apolar, regions, exposed, during, unfolding, '(', 'histidine)'])]). relacion([sujeto(['Higher', levels, of, social, support, positively, correlated, with]), verbo([reported]), complemento([higher, levels, of, life, satisfaction, '(', r, =, 0.483, ',', p, &, 'lt;', 0.001, ')'])]). relacion([sujeto(['Social', support, was]), verbo([found]), complemento([to, be, a, partial, mediator, 'variable,', mediating, approximately, 23.05, '%', of, the, total, effect, of, depression, on, life, satisfaction, '(', 'Sobel', =, -, 3.065, ',', p, =, 0.002, ')'])]). relacion([sujeto(['Informal', social, support, can]), verbo([act]), complemento([as, a, mediator, variable, in, the, relationship, of, depression, and, life, satisfaction, in, caregivers, of, 'AD', patients])]). relacion([sujeto(['Previous', 'cross-sectional', survey, findings, in, the, district, indicated, that, distance, from, facility, and]), verbo([associated]), complemento([costs, are, important, determinants, of, health, facility, attendance, in, the, district])]). relacion([sujeto(['Low', geographic, accessibility, to, facilities]), verbo([inhibited]), complemento(['care-seeking,', sometimes, by, extending, the, '\'', assessment, 'period\'', for, a, 'child\'s', illness, 'episode,', and, led, to, delays, in, seeking, formal, 'treatment,', particularly, when, the, illness, occurred, at, night])]). relacion([sujeto(['Geographic', marginality, and, cultural, norms, intersect, in, remote, areas, both, to]), verbo([increase]), complemento([the, logistical, and, anticipated, financial, barriers, to, utilising, services, and, to, reduce, 'caretakers\'', autonomy, to, act, quickly, once, they, recognize, the, need, for, formal, care])]). relacion([sujeto(['Health', education, campaigns, should, be, based, within, 'communities,', engaging, all]), verbo([involved]), complemento([in, 'treatment-seeking', 'decision-making,', including, men, and, 'grandmothers,', and, should, aim, to, promote, the, ability, of, junior, women, to, influence, the, 'treatment-seeking', process])]). relacion([sujeto(['Environmental', conditions, may, impose, unequal, abiotic, selection, pressures, on, each, 'partner,', destabilising, the, coevolutionary, relationship, and]), verbo([increasing]), complemento([the, extinction, risk, of, one, partner])]). relacion([sujeto(['In', this, study, we, explore, how, the, degree, of, population, mixing, and, resource, supply, affect, 'coevolution-induced', extinction, risk, by, coevolving, replicate, populations, of, 'Pseudomonas', fluorescens, 'SBW25', with, its]), verbo([associated]), complemento([lytic, phage, 'SBW25Ф2', under, four, treatment, regimens, incorporating, low, and, high, resource, availability, with, mixed, or, static, growth, conditions])]). relacion([sujeto(['We', observed, an]), verbo([increased]), complemento([risk, of, phage, extinction, under, population, 'mixing,', and, in, low, resource, conditions])]). relacion([sujeto(['High', levels, of, evolved, bacterial, resistance]), verbo([promoted]), complemento([phage, extinction, at, low, resources, under, both, mixed, and, static, 'conditions,', whereas, phage, populations, could, survive, when, phage, susceptible, bacterial, genotypes, rose, to, high, frequency])]). relacion([sujeto(['These', findings, demonstrate, that, phage, extinction, risk, is, influenced, by, multiple, abiotic, 'conditions,', which, together]), verbo([act]), complemento([to, destabilise, the, 'bacteria-phage', coevolutionary, relationship])]). relacion([sujeto(['Although', a, number, of, natural, materials]), verbo([have]), complemento([been, used, as, hemostatic, 'agents,', many, substances, do, not, act, quickly, enough])]). relacion([sujeto(['Here,', we, created, a, novel, dressings, using, collagen, and, chitosan, with, recombinant, batroxobin, '(', 'r-Bat)', to]), verbo([promote]), complemento([faster, and, more, effective, hemostasis])]). relacion([sujeto(['We', hypothesized, that, 'r-Bat', would]), verbo([promote]), complemento([synergetic, blood, coagulation, because, it, contains, a, blood, coagulation, active, site, different, than, those, of, collagen, and, chitosan])]). relacion([sujeto(['Our', results]), verbo([suggest]), complemento([that, each, substances, can, maintain, hemostatic, properties, while, in, the, mixed, dressings, and, that, our, novel, hemostatic, dressings, promotes, potent, control, of, 'bleeding,', as, demonstrated, by, a, whole, blood, assay, and, rat, hemorrhage, model])]). relacion([sujeto(['This', novel, dressings]), verbo([has]), complemento([enormous, possible, for, rapidly, controlling, bleeding, and, it, improves, upon, the, effect, of, collagen, and, chitosan, used, alone])]). relacion([sujeto(['Despite', the, excellent, hemostatic, properties, of, collagen, and, chitosan, 'pads,', they]), verbo([reported]), complemento([to, brittle, behavior, and, lack, sufficient, hemostatic, effect, within, relevant, time])]). relacion([sujeto(['r-Bat']), verbo([acts]), complemento([as, a, 'thrombin-like', enzyme, in, the, coagulation, cascade])]). relacion([sujeto(['Also', the, materials, in, the, pad]), verbo([have]), complemento([synergetic, effect, because, they, have, different, hemostatic, mechanisms, in, the, coagulation, cascade])]). relacion([sujeto(['This']), verbo([report]), complemento([propose, the, novel, hemostatic, pad, isreasonable, that, a, great, potential, for, excessive, bleeding, injury, and, improve, effects, of, natural, substance, hemostatic, pad])]). relacion([sujeto(['Two', types, of, parasporins]), verbo([have]), complemento([been, 'identified:', the, 'three-domain', 'Cry', toxin, type, and, the, 'β-pore-forming-toxin', '(', 'β-PFT)', type])]). relacion([sujeto(['Crystal', structures, of, representative, members, of, the, two, 'types,', 'PS1Aa1', and, 'PS2Aa1,']), verbo([have]), complemento([been, determined, and, compared, with, those, of, 'well-studied', toxins])]). relacion([sujeto(['PS1Aa1']), verbo([has]), complemento([a, typical, architecture, characteristic, of, the, 'three-domain', insecticidal, 'Cry', 'toxins,', though, it, is, cleaved, into, two, polypeptides])]). relacion([sujeto(['It']), verbo([has]), complemento([an, extra, 'N-terminal', segment, found, only, in, the, inactive, form, of, the, 'Cry', toxins, 'and,', 'hence,', it, is, presumed, to, act, through, another, mechanism, as, an, activator, in, the, apoptotic, signaling, pathway, rather, than, a, 'pore-forming', toxin])]). relacion([sujeto(['This', strongly]), verbo([suggests]), complemento([that, a, 'pore-forming', mechanism, similar, to, that, of, 'β-PFTs', is, involved, in, the, action, of, this, type, of, parasporin])]). relacion([sujeto(['The', structural, comparison, of, 'PS2Aa1', to, other, 'aerolysin-type', 'β-PFTs', indicates]), verbo([conserved]), complemento([oligomerization, and, 'pore-forming', structures, in, domains, 2, and, 3, ',', and, highly, diverse, putative, receptor, binding, region, structures, in, domain, 1, ',', likely, accounting, for, enhanced, cancer, cell, cytotoxicity, as, compared, to, normal, control, cells])]). relacion([sujeto(['The', structural, implications, for, the, mechanism, of, action, and, cellular, specificity, of, both, 'Cry', and, 'β-PFT', type, parasporins, will, be]), verbo([enhanced]), complemento([by, further, experimental, validation])]). relacion([sujeto(['The', polyphenol, resveratrol, '(', 'RSV)', is]), verbo([found]), complemento([in, the, skin, of, red, grapes, and, has, been, reported, to, exhibit, anticancer, properties])]). relacion([sujeto(['The', antitumor, effects, of, 'RSV', in, the, gastrointestinal, tract]), verbo([have]), complemento([gained, considerable, interest, due, to, the, high, exposure, of, this, tissue, to, this, dietary, compound])]). relacion([sujeto(['Although', 'RSV']), verbo([has]), complemento([been, described, to, act, as, a, 'calorie-restriction', 'mimetic,', modulating, energy, metabolism, in, normal, 'tissues,', little, efforts, have, been, done, to, study, the, effects, of, this, polyphenol, in, the, metabolism, of, cancer, cells])]). relacion([sujeto(['Paradoxically,', the, cytotoxic, effects, of, 'RSV', were]), verbo([associated]), complemento([with, an, increase, in, oxygen, consumption, supported, by, mitochondrial, biogenesis, and, increased, fatty, acid, oxidation])]). relacion([sujeto(['This', partial, reversion, of, the, 'Warburg', effect, was, followed, by, hyperpolarization, of, mitochondrial, membrane, and, 'ROS', 'production,']), verbo([leading]), complemento([to, an, increased, apoptosis])]). relacion([sujeto(['Our', results, propose, that, the, anticancer, mechanisms, of, 'RSV', could, reside, in]), verbo([targeting]), complemento([cancer, cell, 'metabolism,', promoting, mitochondrial, electron, transport, chain, overload, 'and,', 'ultimately,', increasing, 'ROS', production])]). relacion([sujeto(['These', peptide, blockers]), verbo([act]), complemento([by, two, principal, manners, -, physical, occlusion, of, the, pore, and, prevention, of, activation, gating])]). relacion([sujeto(['Many', of, the, calcium, 'channel-blocking', peptides]), verbo([have]), complemento([evolved, to, tightly, occupy, their, binding, pocket, on, the, principal, pore, forming, subunit, of, the, 'channel,', often, rendering, block, poorly, reversible])]). relacion([sujeto(['Moreover,', several, of, the, best, characterized, blocking, peptides]), verbo([have]), complemento([developed, a, high, degree, of, channel, subtype, selectivity])]). relacion([sujeto(['Myeloid-derived', suppressor, cells, '(', 'MDSCs)', are, a, group, of, heterogeneous, myeloid, cells, that, can]), verbo([suppress]), complemento([antitumor, immunity])]). relacion([sujeto([3, &, #, 8209, ;, fold]), verbo([increased]), complemento([or, decreased, change, were, differentially, expressed, between, the, experimental, and, control, group, mice])]). relacion([sujeto(['The', levels, of, nine, of, these, differentially]), verbo([expressed]), complemento(['miRNAs,', 'miRNA‑468', '(', 'miR‑486),', 'miR‑192,', 'miR‑128,', 'miR‑125a,', 'miR‑149,', 'miR‑27a,', 'miR‑125b,', 'miR‑350', and, 'miR‑328,', were, also, analyzed, by, 'RT‑qPCR', to, validate, the, microarray, data])]). relacion([sujeto(['Bioinformatics', analyses, revealed, that, these, miRNAs, may]), verbo([act]), complemento([on, various, target, 'genes,', including, 'Adar,', 'Pik3r1,', 'Rybp', and, 'Rabgap1,', to, regulate, the, 'survival,', differentiation, and, the, function, of, 'tumor‑induced', granulocytic, 'MDSCs'])]). relacion([sujeto(['The', results, revealed, microRNAs, and, potential]), verbo([targets]), complemento([that, may, be, vital, for, regulating, 'survival,', differentiation, and, function, of, 'G‑MDSCs', induced, by, 'LLC'])]). relacion([sujeto(['Further', investigation, should, be, performed, to, clarify, the, roles, of, these, microRNAs, in]), verbo([regulating]), complemento(['LLC‑induced', granulocytic, 'MDSCs', and, the, target, genes, that, mediate, their, functions])]). relacion([sujeto(['Protocadherin', genes, '(', 'PCDHs)']), verbo([have]), complemento([been, suggested, to, act, as, tumor, suppressor, genes, in, various, tumor, types])]). relacion([sujeto(['Previous', studies]), verbo([have]), complemento([demonstrated, the, upregulation, of, certain, 'PCDH‑γ', subfamily, genes, in, nodal, and, duodenal, follicular, lymphoma, '(', 'FL)', using, gene, expression, analyses])]). relacion([sujeto(['However,', the, mechanisms, and]), verbo([associated]), complemento([molecular, function, of, 'PCDH‑γ', subfamily, gene, upregulation, in, 'FL', remain, to, be, elucidated])]). relacion([sujeto(['The', 'FL‑derived', cell, line, 'FL18', exhibited, strong, 'PCDHGA3', 'expression,', similar, to, the, patient, 'samples,', and, its, proliferation, was]), verbo([suppressed]), complemento([by, 'PCDHGA3', gene, knockdown])]). relacion([sujeto(['Genes']), verbo([expressed]), complemento([concomitantly, with, 'PCDHGA3', were, selected, from, gene, expression, 'data,', and, 'TNFRSF6B,', a, member, of, the, tumor, necrosis, factor, receptor, 'superfamily,', was, among, the, top, five, most, strongly, correlated, genes])]). relacion([sujeto(['Coexpression', of, 'TNFRSF6B', and, 'PCDHGA3', was, observed, immunohistochemically, in, 'FL18', 'cells,']), verbo([suggesting]), complemento([potential, cooperation, in, tumor, cell, maintenance])]). relacion([sujeto(['In', 'conclusion,', the, results, of, the, present, study, indicated, that, 'PCDHGA3', was]), verbo([expressed]), complemento([in, 'FL', irrespective, of, 'BCL2', status, and, grading, and, was, associated, with, cell, proliferation])]). relacion([sujeto(['Further', studies]), verbo([involving]), complemento([molecular, genetic, analyses, are, required, to, elucidate, the, mechanisms, underlying, the, activity, of, 'PCDHGA3', in, 'FL'])]). relacion([sujeto(['Genome', sequencing, of, large, cohorts, of, tumors]), verbo([has]), complemento([revealed, that, mutations, in, genes, encoding, chromatin, regulators, are, frequent, in, cancer])]). relacion([sujeto(['Here,', we, review, the, current, knowledge, concerning, the, alterations, of, the, 'Polycomb', machinery, in, 'cancer,', with, a, particular, focus, on, the, 'Polycomb', repressive, complex, 2, '(', 'PRC2),', a, key, chromatin, modifier]), verbo([involved]), complemento([in, the, maintenance, of, transcriptional, silencing])]). relacion([sujeto(['A', broad, variety, of, alterations, can, impair, 'PRC2', 'activity;', 'yet,', 'overall,', only, one, type, of, alteration, is]), verbo([found]), complemento([in, a, given, class, of, tumor])]). relacion([sujeto(['We', propose, that, the, distinct, set, of, genes]), verbo([regulated]), complemento([by, 'PRC2,', depending, on, tumor, 'etiology,', constrain, the, type, of, alteration, of, 'PRC2', that, can, fuel, tumor, development])]). relacion([sujeto(['Beyond', this, 'specificity,', we, propose, that, 'PRC2', 'and,', more, 'generally,', chromatin, regulators]), verbo([act]), complemento([as, gatekeepers, of, transcriptional, 'integrity,', a, role, that, often, confers, a, 'tumor-suppressive', function])]). relacion([sujeto(['We', previously]), verbo([reported]), complemento([that, tetrodotoxin, '(', 'TTX)', perfusion, into, the, median, raphe, nucleus, '(', 'MRN),', which, contains, the, cell, bodies, of, serotonin, '(', 5, -, 'HT)', 'neurons,', induced, a, considerable, body, temperature, reduction, under, normal, and, low, ambient, temperatures, '(', 23, and, 5, °, 'C,', 'respectively)', in, freely, moving, rats, but, showed, no, such, effect, under, high, ambient, temperature, '(', 35, °, 'C)'])]). relacion([sujeto(['TTX', perfusion, into, the, 'MRN', or, 'DRN']), verbo([induced]), complemento([significant, hypothermia, '(', from, 37.4, '±0'])]). relacion([sujeto([1, ')', with]), verbo([increased]), complemento([tail, skin, temperature, '(', from, 26.1, '±0'])]). relacion([sujeto(['TTX', perfusion, into, the, 'MRN']), verbo([induced]), complemento([hyperactivity, '(', from, 10.7, '±4'])]). relacion([sujeto([1, ')', ',', whereas, perfusion, into, the, 'DRN']), verbo([induced]), complemento([immobility])]). relacion([sujeto(['Thus,', the, 5, -, 'HT', projections, from, the, 'MRN', and, 'DRN', may, play, similar, roles, in, 'thermoregulation,', both, in, the, heat, production, system, and, in, the, heat]), verbo([loss]), complemento(['system,', but, their, roles, in, the, regulation, of, 'Act', might, be, distinct, and, opposite])]). relacion([sujeto(['Contrast', agents, are, used, to]), verbo([increase]), complemento([the, sensitivity, of, this, technique])]). relacion([sujeto(['Its', derivatives]), verbo([act]), complemento([as, useful, ligands, to, produce, stable, complexes, with, 'Gd(3+)', ion])]). relacion([sujeto(['Better', kinetic, and, thermodynamic, stability, of, 'cyclen-based', 'MRI', contrast, agents]), verbo([decrease]), complemento([their, potential, toxicity, for, in, vivo, use])]). relacion([sujeto(['Consequently,', such, agents]), verbo([have]), complemento([proved, to, be, safest, for, clinical, applications])]). relacion([sujeto(['This', article, elucidates, detailed, strategies, to]), verbo([increase]), complemento([relaxivity, of, 'cyclen-based', 'MRI', contrast, agents])]). relacion([sujeto(['They', also]), verbo([act]), complemento([as, building, blocks, for, the, synthesis, of, novel, ligands])]). relacion([sujeto(['Gd(3+)-chelates', of, such, ligands, prove, to, be, useful, 'MRI', contrast, agents, of]), verbo([enhanced]), complemento(['relaxivity,', greater, 'stability,', better, 'clearance,', lesser, toxicity, and, higher, water, solubility])]). relacion([sujeto(['Here,', we, show, by, analysis, of, conditional, double, mutants, that, the, two, 'T-box', transcription, factor, genes, 'Tbx2', and, 'Tbx3']), verbo([act]), complemento([together, in, the, lung, mesenchyme, to, maintain, branching, morphogenesis])]). relacion([sujeto(['Genetic', rescue, experiments]), verbo([reveal]), complemento([that, 'Tbx2', and, 'Tbx3', function, downstream, 'of Shh', to, maintain, 'pro-proliferative', mesenchymal, 'Wnt', 'signaling,', in, part, by, direct, repression, of, the, 'Wnt', antagonists, 'Frzb', and, 'Shisa3'])]). relacion([sujeto(['In', combination, with, our, previous]), verbo([finding]), complemento([that, 'Tbx2', and, 'Tbx3', repress, 'the cell-cycle', inhibitors, 'Cdkn1a', and, 'Cdkn1b,', we, conclude, that, 'Tbx2', and, 'Tbx3', maintain, proliferation, of, the, lung, mesenchyme, by, way, of, at, least, two, molecular, 'mechanisms:', regulating, 'cell-cycle', regulation, and, integrating, the, activity, of, multiple, signaling, pathways])]). relacion([sujeto(['Near', infrared, laser, is, known, to]), verbo([induce]), complemento([biostimulatory, 'effects,', resulting, in, cell, proliferation, enhancement])]). relacion([sujeto(['Although', such, positive, effect, is, widely, exploited, in, various, clinical, 'applications,', molecular, mechanisms]), verbo([involved]), complemento([are, still, poorly, understood])]). relacion([sujeto(['The', aim, of, the, study, was, to, investigate, the, ability, of, laser, stimulation, to]), verbo([increase]), complemento([cell, proliferation, through, an, early, activation, of, three, redox, sensitive, 'pathways,', namely, 'Nrf-2,', 'NF-κB', and, 'ERK', in, a, rat, 'odontoblast-like', cell, line, '(', 'MDPC-23', 'cells)'])]). relacion([sujeto(['Our', results, show, that, a, single, 25, 'J', laser, stimulation, is, able, to]), verbo([increase]), complemento([cell, proliferation, and, that, this, effect, could, be, increased, by, repeating, the, stimulation, twice, with, a, time, lapse, of, 24, h])]). relacion([sujeto(['Western', blot, experiments, demonstrated, that, laser, stimulation, is, able, to]), verbo([induce]), complemento([an, early, activation, response, in, intracellular, 'signaling,', with, an, overlapping, time, pattern, between, the, three, considered, pathways])]). relacion([sujeto(['Results', discussed, in, this, paper]), verbo([reveal]), complemento([a, complex, mechanism, underlying, 'near-infrared', induced, increase, in, 'pre-odontoblasts', 'proliferation,', involving, three, survival, pathways, that, can, act, both, separately, or, through, reciprocal, crosstalk])]). relacion([sujeto(['In', 'particular,', data, presented]), verbo([suggest]), complemento([an, important, role, for, 'ERK', pathway, that, could, act, directly, by, stimulating, cell, proliferation, but, can, also, induce, both, 'Nrf-2', and, 'NF-κB', 'activation,', acting, as, a, critical, cellular, checkpoint, in, response, to, imbalanced, redox, state, generated, by, a, laser, induced, increase, in, 'ROS', production])]). relacion([sujeto(['The']), verbo([binding]), complemento([parameters, computed, from, the, emission, quenching, data, showed, that, 'AZB', bind, to, 'HSA', and, 'BSA', with, significant, affinity, and, it, was, revealed, that, both, the, serum, proteins, '(', 'HSA', and, 'BSA)', can, bind, 'AZB', at, more, than, one, binding, sites, having, at, least, one, 'high-affinity', binding, site, with, different, affinities, '(', 'non-independent)'])]). relacion([sujeto(['Site-competitive', replacement, experiments, with, specific, site, markers, showed, that, 'AZB']), verbo([binds]), complemento([to, site, 'I', of, 'HSA', and, 'BSA'])]). relacion([sujeto(['AutoDock', based, blind, docking, approach, and, molecular, dynamics, simulation, studies, were, used, to, analyze, the, most, probable]), verbo([binding]), complemento([location, of, 'AZB', in, 'HSA', and, 'BSA'])]). relacion([sujeto(['The', 'AZB']), verbo([induced]), complemento([unfolding, of, 'HSA', and, 'BSA', was, established, by, using, 'absorption,', circular, dichroism, and, 'FT-IR', spectral, studies])]). relacion([sujeto(['The', estrogen, receptor, beta, '(', 'ERβ)', selective, agonist, is, considered, a, promising, candidate, for, the, treatment, of, estrogen, deficiency, symptoms, in, 'ERβ-expressing', 'tissues,', without, the, risk, of, breast, 'cancer,', and, multiple, classes, of, compounds]), verbo([have]), complemento([been, reported, as, 'ERβ', selective, agonists])]). relacion([sujeto([',', isoflavone, 'phytoestrogens)', are, regarded, as, one, of, the, cyclized, analogues, of, isobutestrol, 5, 'b,', and]), verbo([suggest]), complemento([that, other, cyclized, scaffolds, comprising, 5, -, 6, bicyclic, rings, could, also, act, as, selective, 'ERβ', ligands])]). relacion([sujeto(['Subsequent', chiral, resolution, of, 12, a, identified, that, 'R-12a']), verbo([has]), complemento([a, superior, profile, over, 'S-12a'])]). relacion([sujeto(['This', is, comparable, to, diarylpropionitrile, '(', 'DPN)', 5, 'c,', one, of, the, promising, selective, 'ERβ', agonists, and, indicates, that, this, 'indane-based', scaffold]), verbo([has]), complemento([the, potential, to, provide, better, 'ERβ', agonistic, probes])]). relacion([sujeto(['Understanding', language]), verbo([requires]), complemento([more, than, the, use, of, fixed, conventions, and, more, than, decoding, combinatorial, structure])]). relacion([sujeto(['Building', on, developments, in, game, theory, and, probabilistic, 'modeling,', we, describe, the, rational, speech]), verbo([act]), complemento(['(', 'RSA)', framework, for, pragmatic, reasoning])]). relacion([sujeto(['RSA', models]), verbo([provide]), complemento([a, principled, way, to, formalize, inferences, about, meaning, in, 'context;', they, have, been, used, to, make, successful, quantitative, predictions, about, human, behavior, in, a, variety, of, different, tasks, and, 'situations,', and, they, explain, why, complex, 'phenomena,', such, as, hyperbole, and, 'vagueness,', occur])]). relacion([sujeto(['More', 'generally,', they]), verbo([provide]), complemento([a, computational, framework, for, integrating, linguistic, 'structure,', world, 'knowledge,', and, context, in, pragmatic, language, understanding])]). relacion([sujeto(['The', heterometallic, complexes, '(', 'NH4', ')', 2, '[', 'Co(H2', 'O)6', ']', 2, '[', 'V10', 'O28', ']', '⋅4', 'H2', 'O', '(', 1, ')', and, '(', 'NH4', ')', 2, '[', 'Co(H2', 'O)5', '(', 'β-HAla)]2', '[', 'V10', 'O28', ']', '⋅4', 'H2', 'O', '(', 2, ')']), verbo([have]), complemento([been, synthesized, and, used, for, the, preparation, of, mixed, oxides, as, catalysts, for, water, oxidation])]). relacion([sujeto(['Thermal', decomposition, of, 1, and, 2, at, relatively, low, temperatures, '(', &, 'lt;500', °, 'C)']), verbo([leads]), complemento([to, the, formation, of, the, solid, mixed, oxides, 'CoV2', 'O6', /, 'V2', 'O5', '(', 3, ')', and, 'Co2', 'V2', 'O7', /, 'V2', 'O5', '(', 4, ')'])]). relacion([sujeto(['The', complexes, '(', 1, ',', 2, ')', and, heterogeneous, materials, '(', 3, ',', 4, ')']), verbo([act]), complemento([as, catalysts, for, photoinduced, water, oxidation])]). relacion([sujeto(['Structural', maintenance, of, chromosome, 1, alpha, '(', 'SMC1A)', gene]), verbo([has]), complemento([been, reported, to, be, related, to, tumor, development, in, some, types, of, human, cancers])]). relacion([sujeto(['However,', the, misregulation, of, 'SMC1A', and, its, functions, in, 'castration-resistant', prostate, cancer, '(', 'CRPC)']), verbo([have]), complemento([not, been, well, understood])]). relacion([sujeto(['In', the, present, 'study,', we]), verbo([found]), complemento([that, 'SMC1A', was, elevated, in, 'androgen-independent', 'PCa', cell, lines, 'PC-3', and, 'DU-145', compared, to, androgen, sensitive, 'LNCap', and, 22, 'RV1', cells, by, qPCR, and, western, blot, assay])]). relacion([sujeto(['Knockdown', of, 'SMC1A']), verbo([inhibited]), complemento([cell, 'growth,', colony, formation, and, cell, migration, abilities, of, 'PC-3', and, 'DU145', cells, by, 'MTT,', colony, formation, and, transwell, 'assays,', and, affected, cell, cycle, progression, in, 'PC-3', and, 'DU145', cells, by, flow, cytometry])]). relacion([sujeto(['Additionally,', we, also]), verbo([found]), complemento([that, the, expression, of, 'SMC1A', gene, was, higher, in, prostate, cancer, tissues, than, in, the, adjacent, normal, tissues, by, immunohistochemical, 'staining,', and, was, positively, correlated, to, tumor, metastasis, and, recurrence, by, 'Oncomine', database, mining])]). relacion([sujeto(['Taken', 'together,', the, present, study, indicates, that, 'SMC1A', may, play, an, important, role, in, malignant, transformation, of, 'PCa', under, conditions, of, androgen, deprivation, and]), verbo([act]), complemento([as, a, new, target, for, 'PCa', diagnosis, and, treatment])]). relacion([sujeto(['Melatonin', is, synthesized, by, the, pineal, gland, and, is]), verbo([released]), complemento([into, the, blood])]). relacion([sujeto(['In', the, last, several, 'years,', some, studies]), verbo([have]), complemento([shown, that, melatonin, has, anticancer, 'properties;', 'however,', the, mechanisms, behind, the, antitumour, traits, are, 'unclear,', especially, in, pancreatic, cancer])]). relacion([sujeto(['Our', study]), verbo([found]), complemento([that, melatonin, inhibited, cell, 'viability,', suppressed, colony, formation, and, reduced, cell, migration, and, invasion, and, induced, cell, apoptosis, in, 'MIA', 'PaCa‑2', cells])]). relacion([sujeto(['Our', results, showed, that, melatonin, treatment]), verbo([inhibited]), complemento(['NF‑κB', p65, activation])]). relacion([sujeto(['Moreover,', melatonin, treatment]), verbo([activated]), complemento([the, 'mitogen‑activated', protein, kinase, pathways, '(', 'c‑jun', 'N‑terminal', kinase, and, 'extracellular‑regulated', 'kinase 1/2),', which, increased, 'Bax', protein, expression, and, 'caspase‑3', cleavage, and, decreased, 'Bcl‑2', protein, expression])]). relacion([sujeto(['These', new, developments, demonstrate, that, melatonin, plays, a, potential, role, in, anticancer, treatment, and, may]), verbo([act]), complemento([as, an, effective, therapeutic, agent, in, the, future])]). relacion([sujeto(['Previously,', we]), verbo([reported]), complemento([that, 'salicylate-based', analogs, of, bryostatin, protect, cells, from, chikungunya, virus, '(', 'CHIKV)-induced', cell, death])]). relacion([sujeto(['Interestingly,', '\'', 'capping\'', the, hydroxyl, group, at, 'C26', of, a]), verbo([lead]), complemento([bryostatin, 'analog,', a, position, known, to, be, crucial, for, binding, to, and, modulation, of, protein, kinase, 'C', '(', 'PKC),', did, not, abrogate, the, 'anti-CHIKV', activity, of, the, 'scaffold,', putatively, indicating, the, involvement, of, a, pathway, independent, of, 'PKC'])]). relacion([sujeto(['The', work, detailed, in, this, study, demonstrates, that, 'salicylate-derived', analog, 1, and, two, capped, analogs, '(', 2, and, 3, ')', are, not, merely, cytoprotective, 'compounds,', but]), verbo([act]), complemento([as, selective, and, specific, inhibitors, of, 'CHIKV', replication])]). relacion([sujeto(['Further,', a, detailed, comparative, analysis, of, the, effect, of, the, 'non-capped', versus, the, two, capped, analogs, revealed, that, compound, 1]), verbo([acts]), complemento([both, at, early, and, late, stages, in, the, chikungunya, virus, replication, 'cycle,', while, the, capped, analogs, only, interfere, with, a, later, stage, process])]). relacion([sujeto(['Co-dosing', with, the, 'PKC', inhibitors, sotrastaurin, and, 'Gö6976', counteracts, the, antiviral, activity, of, compound, 1, without, affecting, that, of, capped, analogs, 2, and, 3, ',']), verbo([providing]), complemento([further, evidence, that, the, latter, elicit, their, 'anti-CHIKV', activity, independently, of, 'PKC'])]). relacion([sujeto(['Thus,', these, 'salicylate-based', bryostatin, analogs, can]), verbo([inhibit]), complemento(['CHIKV', replication, through, a, 'novel,', yet, still, 'elusive,', 'non-PKC', dependent, pathway])]). relacion([sujeto(['To', investigate, whether, microRNA, '(', 'miRNA)', 'miR-21']), verbo([regulates]), complemento([dimethylarginine, dimethylaminohydrolase, 1, '(', 'DDAH1)', expression, through, binding, 3, '\'', -, 'UTR', region, directly, in, human, umbilical, venous, endothelial, cells, '(', 'HUVECs)', and, to, explore, whether, 'DDAH1-V2/V3', transcripts, can, function, as, microRNA, 'sponge,', thereby, modulating, 'DDAH1-V1', expression])]). relacion([sujeto(['The', 'DDAH1', 3, '\'', -, 'UTR', containing, 'miR-21']), verbo([recognizing]), complemento([sequence, was, cloned, into, 'PmirGLO', 'dual-luciferase', miRNA, target, expression, plasmid, to, construct, 'PmirGLO-miR-21'])]). relacion([sujeto(['MiR-21']), verbo([decreased]), complemento([luciferase, activity, of, 'PmirGLO-miR-21', in, a, 'dose-dependent', manner, '(', 'P < 0'])]). relacion([sujeto([1, for, 50, &, 'nbsp;nM', and, 100, &, 'nbsp;nM', 'miR-21),', and, 'miR-21', inhibitor]), verbo([increased]), complemento([reporter, activity, of, 'PmirGLO-miR-21', and, mRNA, expression, of, all, three, 'DDAH1', transcript, variants, significantly, '(', 'P < 0'])]). relacion([sujeto(['The', degree, of]), verbo([increase]), complemento([in, endogenous, 'DDAH1', mRNA, expression, by, 'miR-21', inhibitor, was, more, obvious, for, 'DDAH1-V3'])]). relacion([sujeto(['Overexpression', of, 'miR-21']), verbo([decreased]), complemento([mRNA, expression, and, mRNA, 'half-life', time, of, all, 'DDAH1', transcripts, significantly, '(', 'P < 0'])]). relacion([sujeto([5, ')', ',', and, 'DDAH1-V2', displayed, significantly]), verbo([decreased]), complemento(['half-life', time, than, 'DDAH1-V1', and, -, 'V3', with, or, without, 'miR-21', transfection, '(', 'P < 0'])]). relacion([sujeto(['MiR-21', '(', 100, &, 'nbsp;nM)']), verbo([decreased]), complemento(['DDAH1', protein, expression, and, eNOS, activity, significantly, '(', 'P < 0'])]). relacion([sujeto(['Transfection', of, 'PmirGLO-miR-21', alone]), verbo([increased]), complemento([intracellular, 'miR-21', expression, by, approximately, 5.6, -, 'fold,', but, only, showed, a, trend, of, increase, in, 'DDAH1', protein, expression])]). relacion([sujeto(['Our', results, confirmed, 'DDAH1', 3, '\'', -, 'UTR', as, a]), verbo([target]), complemento([for, 'miR-21,', and, endogenous, 'miR-21', showed, increased, inhibitory, effect, on, 'DDAH1-V3', transcript])]). relacion([sujeto(['DDAH1', 3, '\'', -, 'UTR,', especially, for, 'DDAH1-V3,', may, function, as, 'miR-21', sponge, to]), verbo([regulate]), complemento(['DDAH1', protein, expression])]). relacion([sujeto(['Modulation', of, 'miR-21-DDAH1', interaction, may]), verbo([provide]), complemento([a, new, approach, for, tackling, cardiovascular, diseases])]). relacion([sujeto(['They']), verbo([provide]), complemento([plants, with, minerals, like, phosphate, 'and,', 'furthermore,', act, as, modulators, of, plant, growth, altering, the, root, developmental, program, '[', 4, ',', 5, ']'])]). relacion([sujeto(['However,', the, precise, mechanisms]), verbo([involved]), complemento([in, this, latter, process, are, not, well, understood])]). relacion([sujeto(['Here,', we, show, that, 'AM', fungi, are, able, to]), verbo([modulate]), complemento([root, cortex, development, in, 'Medicago', truncatula, by, activating, 'a novel', 'GRAS-domain', transcription, 'factor,', 'MIG1,', that, determines, the, size, of, cortical, root, cells])]). relacion([sujeto(['MIG1', expression, peaks, in, 'arbuscule-containing', 'cells,']), verbo([suggesting]), complemento([a, role, in, cell, remodeling, during, fungal, accommodation])]). relacion([sujeto(['Roots', ectopically]), verbo([expressing]), complemento(['MIG1', become, thicker, due, to, an, increase, in, the, number, and, width, of, cortical, cells])]). relacion([sujeto(['MIG1', downregulation]), verbo([leads]), complemento([to, malformed, 'arbuscules,', a, phenotype, rescued, by, 'Δ18DELLA1,', suggesting, that, 'MIG1', intersects, with, the, 'GA', signaling, to, control, cell, morphogenesis, through, 'DELLA1'])]). relacion([sujeto(['Now', we]), verbo([provide]), complemento([evidence, 'that,', together, with, 'MIG1,', 'DELLA1', is, responsible, for, radial, cortical, cell, expansion, during, arbuscule, development])]). relacion([sujeto(['Plexins', '(', 'Plexs)', are, a, large, family, of, phylogenetically]), verbo([conserved]), complemento([guidance, receptors, that, bind, specifically, to, semaphorins, '(', 'Semas),', another, large, family, of, guidance, molecules])]). relacion([sujeto(['In', the, 'Drosophila', embryonic, central, nervous, system, '(', 'CNS),', the, secreted, semaphorins, 'Sema-2a', and, 'Sema-2b', both]), verbo([act]), complemento([as, ligands, for, 'PlexB,', but, mediate, mutually, independent, and, opposite, functions, '(', repulsive, and, attractive, 'guidance,', 'respectively)'])]). relacion([sujeto(['PlexB', is, also, known, to]), verbo([regulate]), complemento([motor, axon, guidance, in, the, embryonic, peripheral, nervous, system, '(', 'PNS)'])]). relacion([sujeto(['Here,', we]), verbo([find]), complemento([that, two, distinct, modes, of, ligand, regulation, underlie, differential, roles, of, 'PlexB', in, 'PNS', motor, axon, pathfinding, during, embryonic, development])]). relacion([sujeto(['Epistasis', analyses, in, the, intersegmental, nerve, b, '(', 'ISNb)', pathway]), verbo([suggest]), complemento([that, 'PlexB', serves, as, a, receptor, for, both, 'Sema-2a', and, 'Sema-2b', and, integrates, their, mutually, dependent, but, opposite, guidance, functions])]). relacion([sujeto(['Furthermore,', we, present, evidence, that, 'PlexB']), verbo([mediates]), complemento([not, only, 'Sema-2a/2b-dependent', guidance, 'functions,', but, also, 'Sema-2a/2b-independent', target, recognition, in, establishing, the, segmental, nerve, a, '(', 'SNa)', motor, axon, pathway])]). relacion([sujeto(['Colorectal', cancer, '(', 'CRC),', one, of, the, most, prevalent, malignant, 'cancers,']), verbo([has]), complemento([high, rates, pf, incidence, and, is, the, fourth, leading, cause, of, 'cancer-related', deaths, for, both, men, and, women, worldwide])]). relacion([sujeto(['miRNA‑330-5p']), verbo([has]), complemento([been, implicated, in, the, progression, of, 'prostate,', neuronal, and, pancreatic, cancers, by, regulating, 'proliferation,', 'migration,', invasion, and, 'epithelial-mesenchymal', transition, of, cells])]). relacion([sujeto(['The', purpose, of, the, present, study, was, to, investigate, the, expression, of, 'miR-330-5p', in, 'CRC', and, identify, its]), verbo([target]), complemento(['gene(s)', that, may, act, in, 'CRC', tumorigenesis])]). relacion([sujeto(['We']), verbo([found]), complemento([that, 'miR-330-5p', expression, was, significantly, lower, in, 'CRC', tissues, than, that, in, adjacent, 'non-tumorous', tissues])]). relacion([sujeto(['Furthermore,', we, identified, 'integrin α5', '(', 'ITGA5)', as, a, new]), verbo([target]), complemento([of, 'miR-330-5p', and, found, that, it, inhibits, 'ITGA5', expression, by, directly, binding, to, the, 3, '\'', &, 'nbsp;untranslated', region, of, 'ITGA5', mRNA])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, downregulation, of, 'miR-330-5p', expression, may, affect, 'CRC', development, via, modulation, of, 'ITGA5', expression])]). relacion([sujeto(['Curcumin,', a, natural, polyphenolic, compound, extracted, from, rhizomes, of, 'Curcuma', longa, '(', 'turmeric),', a, plant, in, the, ginger, family, '(', 'Zingiberaceae)']), verbo([has]), complemento([been, used, worldwide, and, extensively, in, 'Southeast', 'Asia'])]). relacion([sujeto(['Hence,', the, present, study, was, designed, in, order, to, explore, the, possible, neuroprotective, role, of, curcumin, against, rotenone]), verbo([induced]), complemento([cognitive, 'impairment,', oxidative, and, mitochondrial, dysfunction, in, mice])]). relacion([sujeto([')', for, a, period, of, three, weeks, significantly, impaired, cognitive, function, '(', 'actophotometer,', rotarod, and, open, field, 'test),', oxidative, defense, '(']), verbo([increased]), complemento([lipid, 'peroxidation,', nitrite, concentration, and, decreased, activity, of, superoxide, 'dismutase,', catalase, and, reduced, glutathione, 'level)', and, mitochondrial, complex, '(', 'II', and, 'III)', enzymes, activities, as, compared, to, normal, control, group])]). relacion([sujeto(['Curcumin', treated, mice, also, mitigated]), verbo([enhanced]), complemento([acetylcholine, esterase, enzyme, level, as, compared, to, negative, control, group])]). relacion([sujeto(['We']), verbo([found]), complemento([that, curcumin, restored, motor, deficits, and, enhanced, the, activities, of, antioxidant, enzymes, suggesting, its, antioxidant, potential, in, vivo])]). relacion([sujeto(['The', findings, of, the, present, study, conclude, neuroprotective, role, of, curcumin, against, rotenone]), verbo([induced]), complemento(['Parkinson\'s', in, mice, and, offer, strong, justification, for, the, therapeutic, prospective, of, this, compound, in, the, management, of, 'PD'])]). relacion([sujeto(['Endotoxic', shock, is, the, primary]), verbo([cause]), complemento([of, morbidity, and, mortality, in, hospital, 'patients,', creating, an, urgent, need, to, explore, the, mechanisms, involved, in, sepsis])]). relacion([sujeto(['Our', previous, studies, showed, that, 'T-cell', 'immunoglobulin-', and, 'mucin-domain-containing', 'molecule-4', '(', 'Tim-4)', attenuated, the, inflammatory, response, through]), verbo([regulating]), complemento([the, functions, of, macrophages])]). relacion([sujeto(['However,', the, mechanism, by, which, 'Tim-4', does, this]), verbo([has]), complemento([not, been, fully, elucidated])]). relacion([sujeto(['In', this, 'study,', we]), verbo([found]), complemento([that, 'Tim-4', expression, was, increased, in, lipopolysaccharide, '(', 'LPS)-induced', endotoxic, shock])]). relacion([sujeto(['To', investigate, the, function, of, 'Tim-4', in, 'LPS-induced', 'inflammation,', we, further, demonstrated, that, 'Tim-4', attenuated, 'LPS-induced', endotoxic, shock, by]), verbo([inhibiting]), complemento([cytokine, production, by, macrophages])]). relacion([sujeto(['Blocking', expression, of, 'Tim-4', and]), verbo([nuclear]), complemento(['factor-kappa', 'B', '(', 'NF-κB)', signal, inhibition, showed, that, 'Tim-4', inhibited, cytokine, production, via, 'NF-κB', signaling, pathway])]). relacion([sujeto(['This', study, indicates, that, 'Tim-4', may, exert, its, immune, modulation, by]), verbo([regulating]), complemento([inflammatory, factor, secretion, and, might, act, as, a, novel, potential, target, for, inflammatory, 'diseases,', especially, endotoxic, shock])]). relacion([sujeto(['Engineered', nanoparticles, '(', 'NPs)', in, the, environment, can]), verbo([act]), complemento([both, as, 'contaminants,', when, they, are, unintentionally, 'released,', and, as, remediation, agents, when, injected, on, purpose, at, contaminated, sites])]). relacion([sujeto(['The', experimental, data, were, fitted, using, the, numerical, code, 'MNMs', and, the, ionic, 'strength-dependent', transport, was, 'up-scaled', for, a, full, scale, 3, 'D', simulation, of, 'SLGO']), verbo([release]), complemento([and, 'long-term', transport, in, a, heterogeneous, aquifer])]). relacion([sujeto(['MNM3D', showed, to, potentially, represent, a, valid, tool, for, the, prediction, of, the, 'long-term', behavior, of, engineered, nanoparticles]), verbo([released]), complemento([in, the, environment, '(', e])]). relacion([sujeto(['Heat', shock, protein, 27, '(', 'HSP27)', is, a, member, of, the, heat, shock, protein, family, which]), verbo([has]), complemento([been, linked, to, tumour, progression, 'and,', most, 'interestingly,', to, chemotherapy, resistance, in, cancer, patients])]). relacion([sujeto(['Levels', and, activation, of, 'HSP27', and, its, potential]), verbo([associated]), complemento([signalling, pathways, were, evaluated, by, protein, array, and, western, blotting])]). relacion([sujeto(['The', present, study, first, 'identified,', by, way, of, protein, 'array,', that, 'YangZheng', 'XiaoJi', was, able, to]), verbo([inhibit]), complemento([the, phosphorylation, of, 'HSP27', protein, in, cancer, cells])]). relacion([sujeto(['Finally,', knocking, down, 'HSP27', markedly, reduced, the, migration, of, cancer, cells, and]), verbo([increased]), complemento([the, sensitivity, of, cancer, cells, to, the, inhibitory, effect, on, cellular, migration, by, 'YangZheng', 'XiaoJi'])]). relacion([sujeto(['YangZheng', 'XiaoJi', can]), verbo([act]), complemento([as, an, agent, in, first, sensitising, cancer, cells, to, chemotherapy, and, secondly, to, 'overcome,', to, some, 'degree,', chemoresistance, when, used, in, an, appropriate, fashion, in, patients, who, have, active, 'HSP27'])]). relacion([sujeto(['Seven', patients, also, received, a, 'pacemaker;', 1, had, a, ventricular]), verbo([lead]), complemento([and, 6, had, atrial, leads])]). relacion([sujeto(['The', patient, with, the, ventricular]), verbo([lead]), complemento([died, during, 'follow-up'])]). relacion([sujeto(['The', 6, patients, with, atrial]), verbo([leads]), complemento([survived, without, events, at, a, mean, 'follow-up', of, 6.9, years, after, pacemaker, implantation])]). relacion([sujeto(['No', arrhythmic, events, occurred, in, 6, very, young, 'JLNS', patients, who, received, atrial, pacing, in, combination, with]), verbo([increased]), complemento([doses, of, 'beta-blockers', during, 7, -, year, 'follow-up'])]). relacion([sujeto(['If', confirmed, in, additional, 'patients,', this, treatment, strategy, may]), verbo([prevent]), complemento(['life-threatening', arrhythmias, in, this, 'high-risk', patient, group, and, may, act, as, a, bridge, to, insertion, of, a, 2, -, chamber, 'ICD', when, left, cardiac, sympathetic, denervation, is, not, available])]). relacion([sujeto(['The', amphibian, disease, 'chytridiomycosis,']), verbo([caused]), complemento([by, infection, with, the, fungal, pathogen, 'Batrachochytrium', dendrobatidis, '(', 'Bd),', is, implicated, in, the, severe, decline, of, over, 200, amphibian, species])]). relacion([sujeto(['In', species, that]), verbo([have]), complemento([declined, but, not, become, 'extinct,', 'Bd', persists, and, can, cause, substantial, ongoing, mortality])]). relacion([sujeto(['High', rates, of, mortality]), verbo([associated]), complemento([with, 'Bd', may, drive, major, changes, in, host, 'demography,', but, this, process, is, poorly, understood])]). relacion([sujeto(['We']), verbo([found]), complemento([that, 'Bd-infected', populations, have, a, severely, truncated, age, structure, associated, with, very, high, rates, of, annual, adult, mortality])]). relacion([sujeto(['We', document, previously, undescribed, demographic, shifts]), verbo([associated]), complemento([with, a, globally, emerging, pathogen, and, demonstrate, how, these, shifts, alter, host, ecology])]). relacion([sujeto(['Truncation', of, age, structure]), verbo([associated]), complemento([with, 'Bd', effectively, reduces, host, niche, width, and, can, help, explain, the, contraction, of, 'L'])]). relacion([sujeto(['The', 'microglia,', once, thought, only, to, be, supporting, cells, of, the, central, nervous, system, '(', 'CNS),', are, now]), verbo([recognized]), complemento([to, play, essential, roles, in, many, pathologies])]). relacion([sujeto(['A', disturbance, or]), verbo([loss]), complemento([of, 'CNS', homeostasis, causes, rapid, responses, of, the, 'microglia,', which, undergo, a, multistage, activation, process])]). relacion([sujeto(['The']), verbo([activated]), complemento([microglia, change, their, cell, shapes, and, gene, expression, 'profiles,', which, induce, 'proliferation,', 'migration,', and, the, production, of, 'pro-', or, antinociceptive, factors])]). relacion([sujeto(['The', cells]), verbo([release]), complemento([a, large, number, of, mediators, that, can, act, in, a, manner, detrimental, or, beneficial, to, the, surrounding, cells, and, can, indirectly, alter, the, nociceptive, signals])]). relacion([sujeto(['Our', objective, was, to, identify, new, molecular]), verbo([targets]), complemento([that, may, result, in, the, development, of, powerful, tools, to, control, the, signaling, associated, with, neuropathic, pain])]). relacion([sujeto(['The', 'FK506-binding', protein, 14, '(', 'FKBP14)', is, a, subfamily, of, 'immunophilins,']), verbo([has]), complemento([been, implicated, in, various, biochemical, processes])]). relacion([sujeto(['Here,', we]), verbo([reported]), complemento([that, 'FKBP14', may, be, an, oncogene, as, it, overexpressed, in, osteosarcoma, tissues, and, cell, 'lines,', and, 'FKBP14', expression, was, correlated, with, 'metastases,', 'recurrence,', tumor, maximum, diameter, and, poor, survival, time])]). relacion([sujeto(['FKBP14', was]), verbo([associated]), complemento([with, the, biological, pathways, including, cell, 'cycle,', apoptosis, and, metastasis])]). relacion([sujeto(['Furthermore,', we, detected, 'FKBP14', knockdown]), verbo([induced]), complemento([cell, cycle, 'arrest,', 'apoptosis,', invasion, and, adhesion, in, vitro])]). relacion([sujeto(['FKBP14', knockdown]), verbo([decreased]), complemento([the, protein, levels, of, 'PCNA,', 'CDK1', and, 'CCNB1', that, promotes, cell, 'cycle,', increased, 'Bax,', 'caspase-3', and, 'caspase-7', protein, involved, in, promoting, cell, 'apoptosis,', and, increased, 'KIF4A', expression, as, well, as, decreased, 'SMC4', and, 'TMEM33', proteins, that, contribute, to, cell, invasion, and, adhesion])]). relacion([sujeto(['In', 'addition,', 'FKBP14', knockdown, also]), verbo([caused]), complemento([a, significant, inhibition, in, tumor, growth, in, vivo])]). relacion([sujeto(['Then,', we]), verbo([found]), complemento([that, the, protein, 'RhoA', was, identified, as, a, binding, partner, of, 'FKBP14'])]). relacion([sujeto(['Taken', 'together,', 'FKBP14', may]), verbo([act]), complemento([as, an, oncogene, in, osteosarcoma, via, suppressing, apoptosis, and, promoting, invasion, and, adhesion, in, osteosarcoma, carcinogenesis])]). relacion([sujeto(['FKBP14', may, be, a, prognostic, factor, and, potential]), verbo([target]), complemento([for, osteosarcoma, treatment])]). relacion([sujeto(['This', receptor, tyrosine, kinase, is, upregulated, in, 10, -, 20, '%', of, esophageal, squamous, cell, carcinoma, '(', 'ESCC)', 'tissues,', and, amplification, of, 'ERBB2']), verbo([has]), complemento([been, correlated, with, poor, prognosis, in, esophageal, cancer])]). relacion([sujeto(['Tissues', from, 131, 'ESCC', 'patients,', along, with, cell, and, animal, models, of, the, disease, were, used, to, probe, the, underlying, mechanisms, by, which, 'ERBB2', upregulation, occurs, and]), verbo([causes]), complemento([negative, outcomes, in, 'ESCC'])]). relacion([sujeto(['We']), verbo([found]), complemento([that, overexpression, of, 'ERBB2', inhibited, radiosensitivity, in, vitro])]). relacion([sujeto(['Furthermore,', 'miR-193a-5p', reduced, 'ERBB2', expression, by, directly]), verbo([targeting]), complemento([the, 3, '\'', 'UTR'])]). relacion([sujeto(['Increased', 'miR-193a-5p']), verbo([enhanced]), complemento([radiosensitivity, and, inhibited, tumorigenesis, in, vitro, and, in, vivo])]). relacion([sujeto(['Our', data]), verbo([suggest]), complemento([that, patients, with, high, 'miR-193a-5p', will, likely, benefit, from, 'CCRT', treatment, 'alone,', however, a, combination, of, 'CCRT', with, 'Herceptin', may, be, beneficial, for, patients, with, low, 'miR-193a-5p', expression])]). relacion([sujeto(['Vascular', mimicry, '(', 'VM)', refers, to, the, plasticity, of, aggressive, cancer, cells, forming, de, novo, vascular, 'networks,', which]), verbo([promoted]), complemento([tumor, metastasis])]). relacion([sujeto(['Positive', 'VM', staining, occurred, in, 19.3, '%', '(', 39, of, 202, ')', 'UCB', 'cases,', and, it, was]), verbo([associated]), complemento([with, increased, risks, of, recurrence, '(', 'Log-Rank', 'p<0'])]). relacion([sujeto(['Recent', studies]), verbo([have]), complemento([suggested, 'Panax', ginseng, has, a, wide, range, of, beneficial, effects, on, 'aging,', central, nervous, system, 'disorders,', and, neurodegenerative, diseases])]). relacion([sujeto(['This', work, aimed, to, screen, for, the, bioactive, components, in, 'Panax', ginseng, that]), verbo([act]), complemento([against, neurodegenerative, 'diseases,', using, the, target, 'cell-based', bioactivity, screening, method])]). relacion([sujeto(['Then']), verbo([target]), complemento(['cell-based', bioactivity, screening, method, was, developed, to, predict, the, candidate, compounds, in, ginseng, with, 'SH-SY5Y', cells])]). relacion([sujeto(['The']), verbo([target]), complemento(['cell-based', bioactivity, screening, method, coupled, with, 'UPLC-QTOF-MS', technique, has, suitable, sensitivity, and, it, can, be, used, as, a, screening, tool, for, low, content, bioactive, constituents, in, natural, products])]). relacion([sujeto(['ERα', is]), verbo([regulated]), complemento([by, a, number, of, mechanisms, including, the, level, of, mRNA, '(', 'Esr1)', expression])]). relacion([sujeto(['For', this, 'study,', we, took, advantage, of, regional, differences, in, hippocampal, 'ERα', expression, to, investigate, 'DNA', 'ERα', promoter, methylation, at, 'CpG', dinucleotide, sites, as, a, potential, epigenetic, mechanism, for]), verbo([regulating]), complemento([gene, expression])]). relacion([sujeto(['The', results, indicate, that, reduced, 'Esr1', expression, in, region, 'CA1', relative, to, 'CA3', was]), verbo([associated]), complemento([with, an, increase, in, 'DNA', methylation, in, region, 'CA1,', particularly, for, the, first, 'CpG', site])]). relacion([sujeto(['Additionally,', differential, methylation, of, distal, 'CpG', 'sites,', 11, -, 17, ',', was]), verbo([associated]), complemento([with, altered, 'Esr1', expression, during, aging, or, following, 'long-term', hormone, deprivation])]). relacion([sujeto(['The', results, support, the, idea, that, methylation, of, site, 1, may, be, the, primary, regulatory, region, for, 'cross-regional', patterns, in, 'ERα', 'expression,', while, distal, sites, are, modifiable, across, the, life, span, and, may]), verbo([act]), complemento([as, a, feedback, mechanism, for, 'ERα', activity])]). relacion([sujeto(['The', lack, of, systematic, analyses, of, integration, experiences, and, of, integration, processes, may]), verbo([act]), complemento([as, an, impediment, to, achieving, more, effective, 'NTD', programming])]). relacion([sujeto(['We', evaluated, differences, in, the, 'definitions,', 'roles,', perceived, 'effectiveness,', and, implementation, experiences, of, integrated, 'NTD', programs, among, a, variety, of, 'NTD', stakeholder, 'groups,', including, multilateral, 'organizations,', funding, 'partners,', implementation, 'partners,', national, 'Ministry', of, 'Health', '(', 'MOH)', 'teams,', district, 'MOH', 'teams,', volunteer, rural, health, 'workers,', and, community, members]), verbo([participating]), complemento([in, 'NTD', campaigns])]). relacion([sujeto(['Coding', of, themes]), verbo([involved]), complemento([a, mix, of, applying, 'in-vivo', open, coding, and, a, priori, thematic, coding, from, a, start, list])]). relacion([sujeto(['In', 'general,', stakeholder, groups]), verbo([provided]), complemento([unique, 'perspectives,', rather, than, contrarian, points, of, 'view,', on, the, same, topics])]). relacion([sujeto(['Qualitative', data]), verbo([suggest]), complemento([several, 'structural,', 'process,', and, technical, opportunities, that, could, be, addressed, to, promote, more, effective, and, efficient, integrated, 'NTD', elimination, programs])]). relacion([sujeto(['Appointments', for, pain, management, were, for, a, patient, who, sustained, an, ankle, fracture]), verbo([requiring]), complemento([surgery, and, experiencing, difficulty, weaning, off, opioids])]). relacion([sujeto(['The', 'serine/threonine', kinases, 'ROCK1', and, 'ROCK2', are, central, mediators, of, actomyosin, contractile, force, generation, that]), verbo([act]), complemento([downstream, of, the, 'RhoA', small, 'GTP-binding', protein])]). relacion([sujeto(['As', a, 'result,', they]), verbo([have]), complemento([key, roles, in, regulating, cell, morphology, and, 'proliferation,', and, have, been, implicated, in, numerous, pathological, conditions, and, diseases, including, hypertension, and, cancer])]). relacion([sujeto(['This', 'two-stage', system, of, regulation, allows, for, 'tissue-selective', expression, of, the, 'ROCK2:ER', fusion, 'protein,', which, then]), verbo([requires]), complemento([administration, of, estrogen, analogues, such, as, tamoxifen, or, 4, -, hydroxytamoxifen, to, elicit, kinase, activity])]). relacion([sujeto(['This', conditional, 'gain-of-function', system, was, validated, in, multiple, tissues, by, crossing, with, mice]), verbo([expressing]), complemento(['CRE', recombinase, under, the, transcriptional, control, of, cytokeratin14, '(', 'K14),', murine, mammary, tumor, virus, '(', 'MMTV)', or, cytochrome, 'P450', 'Cyp1A1', '(', 'Ah)', 'promoters,', driving, appropriate, expression, in, the, 'epidermis,', mammary, or, intestinal, epithelia, respectively])]). relacion([sujeto(['Cotinine', is, the, major, metabolite, of, nicotine, and]), verbo([has]), complemento([displayed, some, capacity, for, improving, cognition, in, mouse, models, following, chronic, administration])]). relacion([sujeto(['Acute', cotinine, treatment]), verbo([increased]), complemento([the, inhibitory, 'serine-phosphorylation', of, 'GSK3β', and, the, activating, phosphorylation, of, 'AKT,', which, can, mediate, 'serine-phosphorylation', of, 'GSK3β,', in, both, 'wild-type', and, 'Fmr1(-/-)', mouse, hippocampus])]). relacion([sujeto(['However,', cotinine, failed, to, restore, impaired, cognition, in, 'GSK3β', knockin, 'mice,', in, which, a, 'serine9-to-alanine9', mutation, blocks, the, inhibitory, serine, phosphorylation, of, 'GSK3β,']), verbo([causing]), complemento(['GSK3β', to, be, hyperactive])]). relacion([sujeto(['These', results, indicate, that, acute, cotinine, treatment, effectively, repairs, impairments, of, these, four, cognitive, tasks, in, 'Fmr1(-/-)', 'mice,', and]), verbo([suggest]), complemento([that, this, 'cognition-enhancing', effect, of, cotinine, is, linked, to, its, induction, of, inhibitory, 'serine-phosphorylation', of, 'GSK3'])]). relacion([sujeto(['Taken', 'together,', these, results, show, that, nicotinic, receptor, agonists, can]), verbo([act]), complemento([as, cognitive, enhancers, in, a, mouse, model, of, 'Fragile', 'X', syndrome, and, highlight, the, potential, role, of, inhibiting, 'GSK3β', in, mediating, the, beneficial, effects, of, cotinine, on, memory])]). relacion([sujeto(['As', the, medical, community, awaits, the]), verbo([release]), complemento([of, final, rules, to, implement, the, new, 'Medicare', payment, system, under, the, 'Medicare', 'Access', and, 'CHIP', 'Reauthorization', 'Act', '(', 'MACRA),', physicians, can, take, steps, now, to, prepare, for, the, transition])]). relacion([sujeto(['One', of, the, goals, of, the, 'Affordable', 'Care', 'Act', aims, to]), verbo([provide]), complemento([affordable, health, insurance, through, the, health, insurance, exchange, marketplace, '(', the, 'Marketplace)'])]). relacion([sujeto(['GSPE', components]), verbo([act]), complemento([by, activating, the, 'Glucagon-like', 'peptide-1', '(', 'GLP-1)', receptor, because, their, effect, is, blocked, by, 'Exendin', 9, -, 39])]). relacion([sujeto(['GSPE', in, turn]), verbo([acts]), complemento([on, the, hypothalamic, center, of, food, intake, control, probably, because, of, increased, 'GLP-1', production, in, the, intestine])]). relacion([sujeto(['To', 'conclude,', 'GSPE']), verbo([inhibits]), complemento([food, intake, through, 'GLP-1', 'signaling,', but, it, needs, to, be, dosed, under, optimal, conditions, to, exert, this, effect])]). relacion([sujeto(['In', the, infected, human, 'hepatocyte,', expression, of, the, hepatitis, 'B', virus, '(', 'HBV)', accessory, protein, 'X', '(', 'HBx)', is, essential, to]), verbo([maintain]), complemento([viral, replication, in, vivo])]). relacion([sujeto(['HBx', critically]), verbo([interacts]), complemento([with, the, host, damaged, 'DNA', binding, protein, 1, '(', 'DDB1)', and, the, associated, ubiquitin, ligase, 'machinery,', suggesting, that, 'HBx', functions, by, inducing, the, degradation, of, host, proteins])]). relacion([sujeto(['One', 'HBx']), verbo([interacting]), complemento(['protein,', 'talin-1', '(', 'TLN1),', was, proteasomally, degraded, upon, 'HBx', expression])]). relacion([sujeto(['Further', analysis, showed, that, 'TLN1', levels, indeed]), verbo([modulate]), complemento(['HBV', transcriptional, activity, in, an, 'HBx-dependent', manner])]). relacion([sujeto(['This', indicates, that, 'HBx-mediated', 'TLN1', degradation, is, essential, and, sufficient, to]), verbo([stimulate]), complemento(['HBV', replication])]). relacion([sujeto(['Our', data, show, that, 'TLN1', can]), verbo([act]), complemento([as, a, viral, restriction, factor, that, suppresses, 'HBV', 'replication,', and, suggest, that, the, 'HBx', relieves, this, restriction, by, inducing, 'TLN1', degradation])]). relacion([sujeto(['This', work, first]), verbo([reports]), complemento([the, preparation, of, 'super-amphiphilic', 'silica-nanogel', composites, to, reduce, the, contact, angle, of, water, to, increase, the, diffusion, of, pollutant, into, adsorbents])]). relacion([sujeto(['The', feasibility, of, silica, polyacrylamide, nanogel, composites, to]), verbo([act]), complemento([as, a, 'high-performance', adsorbent, for, removal, of, methylene, blue, '(', 'MB)', dye, and, heavy, metals, '(', 'Co(2+)', and, 'Ni(2+))', from, aqueous, solution, was, investigated])]). relacion([sujeto(['The', surface, 'tension,', contact, 'angle,', average, pore, 'size,', and, zeta, potential, of, the, 'silica-nanogel', composites]), verbo([have]), complemento([been, evaluated])]). relacion([sujeto(['This']), verbo([finding]), complemento([is, alarming, as, higher, levels, of, 'PA,', already, at, four, years, of, 'age,', seem, to, reduce, the, risk, of, childhood, obesity, and, provides, 'long-term', health, benefits])]). relacion([sujeto(['Vigorous', exercises, were, 'gender-typed', as, masculine, while, girls, had, to]), verbo([maintain]), complemento([an, aesthetic, appearance, at, all, times])]). relacion([sujeto(['This', contributed, to, a]), verbo([decrease]), complemento([in, 'girls\'', desire, to, engage, in, physical, activities])]). relacion([sujeto(['Among', 'males,', there, is, also, a, budding, tolerance, of, female, participation, in, vigorous, 'sports,', as, long, as, girls]), verbo([maintained]), complemento([a, feminine, stereotype, outside, their, participation])]). relacion([sujeto(['Self-objectification', influenced, 'Costa', 'Rican', adolescent, 'girls\'', decisions, to]), verbo([participate]), complemento([in, physical, activities])]). relacion([sujeto(['Limited', research]), verbo([has]), complemento([examined, park, use, and, physical, activity, among, economically, and, ethnically, diverse, families])]). relacion([sujeto(['Half', of, respondents, were, sufficiently, 'active;', 87.6, '%']), verbo([reported]), complemento([park, use, in, the, prior, 6, months])]). relacion([sujeto(['Among', sufficiently, active, 'respondents,', 92.4, '%']), verbo([reported]), complemento([park, use, '(', 'p='])]). relacion([sujeto(['We']), verbo([found]), complemento([no, difference, in, park, proximity, between, respondents, who, did, and, did, not, report, distance, as, a, park, use, barrier])]). relacion([sujeto(['An', objective, assessment, confirmed, fewer, activity, features, in, parks, near, the, homes, of, respondents]), verbo([reporting]), complemento([few, activity, features, as, a, barrier, to, park, use])]). relacion([sujeto(['Efforts', to]), verbo([promote]), complemento(['families\'', awareness, of, park, locations, might, be, warranted, to, reduce, perceived, proximity, barriers])]). relacion([sujeto(['In', an, effort, to, change, 'this,', the, term, &, 'quot;active', 'play"']), verbo([has]), complemento([been, used, to, promote, increased, physical, activity, levels])]). relacion([sujeto(['Nine', studies]), verbo([provided]), complemento([a, definition, or, description, of, active, 'play,', six, measured, active, 'play,', and, 13, included, both, outcomes])]). relacion([sujeto(['While', variability, in, active, play, definitions, did, 'exist,', common, themes, 'included:']), verbo([increased]), complemento([energy, 'exerted,', rough, and, 'tumble,', gross, motor, 'movement,', 'unstructured,', freely, 'chosen,', and, fun])]). relacion([sujeto(['As', 'such,', an, accepted, and, consistent, definition, is, 'necessary,', which, we]), verbo([provide]), complemento([herein])]). relacion([sujeto(['Concomitant', serious, diseases, significantly]), verbo([decrease]), complemento([the, level, of, 'PA', of, older, subjects])]). relacion([sujeto(['Public', parks, hold, promise, for]), verbo([promoting]), complemento(['population-level', 'PA,', but, studies, show, a, significant, portion, of, park, use, is, sedentary])]). relacion([sujeto(['Past', research]), verbo([has]), complemento([documented, the, effectiveness, of, 'message-based', strategies, for, influencing, diverse, behaviors, in, park, settings, and, for, increasing, 'PA', in, 'non-park', contexts])]). relacion([sujeto([',', 'point-of-decision', 'prompts)', to]), verbo([increase]), complemento(['park-based', 'PA,', the, purpose, of, this, study, was, to, elicit, insights, about, key, 'attitudes,', perceived, 'norms,', and, personal, agency, that, affect, park, use, and, 'park-based', 'PA', in, 'low-income', urban, neighborhoods])]). relacion([sujeto(['Information', about, 'attitudes,', perceived, 'norms,', and, personal, agency, can]), verbo([increase]), complemento([understanding, of, 'theoretically-derived', factors, that, influence, 'park-based', 'PA', and, help, park, and, health, professionals, create, communication, strategies, to, promote, 'PA'])]). relacion([sujeto(['At', 'baseline,', 68.8, '%', of, participants, were, overweight, or, 'obese,', 93.8, '%']), verbo([reported]), complemento([food, 'insecurity,', and, 43.8, '%', reported, activity, levels, below, physical, activity, guidelines])]). relacion([sujeto(['Most', participants]), verbo([reported]), complemento([that, the, intervention, was, helpful, for, increasing, 'fruit/vegetable', intake, and, physical, activity])]). relacion([sujeto(['Findings', highlight, the, potential, to, improve, dietary, quality, and]), verbo([increase]), complemento([physical, activity, among, sheltered, homeless, adults])]). relacion([sujeto([&, 'lt;', 1, 'hr)', of, sedentary, time, was, independently]), verbo([associated]), complemento([with, lower, 'DSST', scores, '(', β, =, -, 3.1, ;, 95, '%', 'CI:', -, 5.8, to, -, 0.4, ;, 'P=0'])]). relacion([sujeto(['Accumulated', daily, sedentary, behavior, of, 5, +, hrs, is]), verbo([associated]), complemento([with, lower, cognitive, function, in, an, older, adult, population, when, physical, activity, is, not, taken, into, account])]). relacion([sujeto(['Efforts', should, be, made, to]), verbo([promote]), complemento([physical, activity, in, the, aging, population])]). relacion([sujeto(['Evidence']), verbo([has]), complemento([shown, that, physical, activity, '(', 'PA)', is, associated, with, low, mortality, risk])]). relacion([sujeto(['Medical', records, were, used, to, identify, the]), verbo([cause]), complemento([of, the, death])]). relacion([sujeto(['The', most, prevalent]), verbo([cause]), complemento([of, death, was, circulatory, system, diseases, '(', 'n=20;', 33.9, '%', '[', 21.8, '%', to, 45.9, '%', ']', ')'])]). relacion([sujeto(['Higher', scores, of, occupational, '(', 'HR=', 0.45, '[', 95, '%', 'CI:', 0.2, to, 0.97, ']', ')', ',', sports, '(', 'HR=', 0.44, '[', 95, '%', 'CI:', 0.2, to, 0.95, ']', ')', and, overall, 'PA', '(', 'HR=', 0.4, '[', 95, '%', 'CI:', 0.17, to, 0.9, ']', ')', were]), verbo([associated]), complemento([with, lower, 'mortality,', even, after, adjustment, for, confounders])]). relacion([sujeto(['Proximity', to, urban, green, spaces, '(', 'UGS)', and, open, sports, spaces, '(', 'OSS)', benefits, 'health,']), verbo([promotes]), complemento([physical, activity, '(', 'PA)', and, sports, practice, '(', 'SP)'])]). relacion([sujeto(['Regarding', 'vicinity\'', of, 'schools,', the, prevalence, of, 'moderate/vigorous', 'PA', among, 'boys,']), verbo([decreases]), complemento([as, distances, to, 'OSS', increases])]). relacion([sujeto(['For', 'girls,', the, prevalence, of, sports]), verbo([decreases]), complemento([as, distances, to, 'UGS', increase])]). relacion([sujeto(['For', 'boys,', we]), verbo([found]), complemento([an, association, between, 'moderate/vigorous', 'PA', and, proximity, to, 'OSS', in, the, vicinity, of, 'schools:', considering, '≤250m', as, 'reference,', the, odds, of, 'moderate/vigorous', 'PA', is, 0.2, '(', 0.06, -, 0.63, ')', for, &, 'gt;250m', 'to≤500m;', 0.21, '(', 0.07, -, 0.61, ')', for, &, 'gt;500m', 'to≤750m', and, 0.19, '(', 0.06, -, 0.58, ')', for, &, 'gt;750m'])]). relacion([sujeto(['Vicinities', of, schools, seem, to, influence, teenagers, to, be, more, physical, active, and]), verbo([increase]), complemento([sports, participation])]). relacion([sujeto(['No', significant, relationship, was]), verbo([found]), complemento([between, adequate, physical, activity, and, distant, green, space])]). relacion([sujeto(['No', significant, relationships, were]), verbo([found]), complemento([between, adequate, physical, 'activity,', engaging, in, 'MVPA,', and, local, green, space])]). relacion([sujeto(['Our', findings, also]), verbo([suggest]), complemento([that, moderate, size, of, local, green, space, together, with, moderate, size, of, distant, green, space, are, important, lever, for, participation, of, physical, activity])]). relacion([sujeto(['Adjusted', odds, ratios, and, 95, '%', confidence, intervals, for]), verbo([reporting]), complemento([an, increase, of, '≥10', min, 'past-week', physical, activity, and, workday, physical, activity, among, those, with, new, showers, and, existing, showers, relative, to, those, with, no, showers, were, also, assessed])]). relacion([sujeto(['One-quarter', of, participants, with, new, workplace, showers, and, 46.9, '%', of, those, with, existing, workplace, showers, at, baseline]), verbo([reported]), complemento([ever, using, the, showers])]). relacion([sujeto(['This', prospective, study, did, not]), verbo([find]), complemento([significant, changes, in, employee, physical, activity, four, months, after, installation, of, worksite, showers])]). relacion([sujeto(['Worksite', shower, users, were, highly, active, at, 'baseline,']), verbo([suggesting]), complemento([a, possible, early, adopter, 'effect,', with, potential, for, diffusion])]). relacion([sujeto(['Results', 'Children', exposed, to, the, multicomponent, intervention]), verbo([increased]), complemento([their, time, spent, in, light, 'PA', '(', +, 5.9, '%', ')', during, recess])]). relacion([sujeto(['In', 'depth-analyses', on, intervention, components, showed, that, physical, schoolyard, interventions, particularly, predicted, a]), verbo([decrease]), complemento([in, time, spent, in, sedentary, behavior, during, recess, at, 'follow-up'])]). relacion([sujeto(['Seventy-five', percent, of, respondents]), verbo([reported]), complemento([walking, for, either, transportation, '(', 54, '%', ')', or, leisure, '(', 56, '%', ')', in, the, past, 'week,', 59, '%', reported, no, safety, 'concern,', and, 36, '%', reported, absence, of, any, built, environment, attribute, of, walkability, nearby])]). relacion([sujeto(['Respondents', with, more, 'education,', and, those, who, lived, in, metropolitan, areas, were, more, likely, to]), verbo([report]), complemento([built, environment, attributes, supportive, of, walking])]). relacion([sujeto(['All', built, environment, attributes, 'examined,', as, well, as, safety, concern, due, to, speeding, 'vehicles,', were]), verbo([associated]), complemento([with, walking, after, adjustment, for, demographic, characteristics])]). relacion([sujeto(['Walking,', particularly, for, 'transportation,', is]), verbo([associated]), complemento([with, many, built, environment, attributes, among, 'U'])]). relacion([sujeto(['In', order, to, overcome, one, of, the, greatest, challenges, in, malaria, 'treatment,', drug, 'resistance,', new, drug, candidates, are, urgently, 'needed,', which, should, preferably]), verbo([act]), complemento([via, novel, mechanisms])]). relacion([sujeto(['Successful', optimization, of, a, phenotypic, screening, hit, based, on, a, 'quinoline-4-carboxamide', derivative, resulted, in, the, highly, promising]), verbo([lead]), complemento([structure, 4, ',', which, according, to, the, 'Medicines', for, 'Malaria', 'Venture', '(', 'MMV)', met, the, efficacy, and, drug, metabolism, and, pharmacokinetics, '(', 'DMPK)', requirements, for, a, malaria, drug, target, candidate, and, consequently, was, selected, for, preclinical, development])]). relacion([sujeto(['The', 'temperature-driven', 'fluid-to-gel', and, 'gel-to-fluid', phase, transitions, of, the, fatty, acids, within, the, bridge]), verbo([act]), complemento([as, a, thermal, switch, for, cluster, assembly, and, disassembly])]). relacion([sujeto(['This', method, of]), verbo([binding]), complemento([particles, is, 'simple,', 'robust,', and, generic, and, can, be, extended, further, to, assemble, particles, with, nonspherical, shapes, and, complex, surface, chemistries, enabling, the, formation, of, sophisticated, colloidal, molecules])]). relacion([sujeto(['Little', is, known, with, certainty, about, the, mechanisms, of, idiosyncratic, drug, reactions, '(', 'IDRs);', 'however,', there, is, substantive, evidence, that, reactive, metabolites, are]), verbo([involved]), complemento([in, 'most,', but, not, 'all,', 'IDRs'])]). relacion([sujeto(['In', 'addition,', evidence, also]), verbo([suggests]), complemento([that, most, 'IDRs', are, immune, mediated])]). relacion([sujeto(['That', raises, the, question, of, how, reactive, metabolites]), verbo([induce]), complemento([an, immune, response, that, can, lead, to, an, 'IDR'])]). relacion([sujeto(['These', are, complementary, 'hypotheses:', a, reactive, metabolite, can]), verbo([act]), complemento([as, a, hapten, to, produce, 'neoantigens,', and, it, can, also, cause, cell, damage, leading, to, the, release, of, 'danger-associated', molecular, pattern, molecules, that, activate, antigen, presenting, cells])]). relacion([sujeto(['Both', are]), verbo([required]), complemento([for, an, immune, response])]). relacion([sujeto(['In', 'addition,', drugs, may]), verbo([induce]), complemento([an, immune, response, through, inflammasome, activation])]). relacion([sujeto(['We']), verbo([have]), complemento([found, examples, in, which, the, ability, to, activate, inflammasomes, differentiated, drugs, that, cause, 'IDRs', from, similar, drugs, that, do, not])]). relacion([sujeto(['There', are, other, hypotheses, that, do, not]), verbo([involve]), complemento([an, immune, mechanism, such, as, mitochondrial, injury, and, bile, salt, export, pump, '(', 'BSEP)', inhibition])]). relacion([sujeto(['Consistent', with, this, 'hypothesis,', we, used, checkpoint, inhibition, to, develop, the, first, animal, model, of, idiosyncratic, 'drug-induced', liver, injury, that]), verbo([has]), complemento([the, same, characteristics, as, the, idiosyncratic, injury, in, humans])]). relacion([sujeto(['The', combination, of, the, 'Pd-1-/-', mouse, and, 'anti-CTLA-4', also, unmasks, the, ability, of, other, drugs, such, as, isoniazid, to]), verbo([cause]), complemento([delayed, type, liver, injury])]). relacion([sujeto(['There', is, an, urgent, need, to, develop, potent, and, selective, inhibitors, of, bacterial, 'ACs', with, prospects, for, the, development, of, potential, antibacterial, therapeutics, and, to, study, their, molecular, interactions, with, the]), verbo([target]), complemento([enzymes])]). relacion([sujeto(['Fluorescence', experiments, indicated, that, 'Cl-ANT-ANPpp', analogues]), verbo([bind]), complemento([to, the, 'ACT', active, 'site,', and, docking, studies, suggested, that, the, 'Cl-ANT', group, interacts, with, 'Phe306', and, 'Leu60'])]). relacion([sujeto(['Interestingly,', the]), verbo([increase]), complemento([in, direct, fluorescence, with, 'Cl-ANT-ANPpp', having, an, ester, linker, was, strictly, calmodulin, '(', 'CaM)-dependent,', whereas, 'Cl-ANT-ANPpp', analogues, with, an, amide, 'linker,', upon, binding, to, 'ACT,', increased, the, fluorescence, even, in, the, absence, of, 'CaM'])]). relacion([sujeto(['Such', a, dependence, of]), verbo([binding]), complemento([on, structural, modification, could, be, exploited, in, the, future, design, of, potent, inhibitors, of, bacterial, 'ACs'])]). relacion([sujeto(['Furthermore,', one, 'Cl-ANT-ANP', in, the, form, of, a, bisamidate, prodrug, was, able, to]), verbo([inhibit]), complemento(['B'])]). relacion([sujeto(['Climate', shifts, at, decadal, scales, can]), verbo([have]), complemento([environmental, 'consequences,', and, 'therefore,', identifying, areas, that, act, as, environmental, refugia, is, valuable, in, understanding, future, climate, variability])]). relacion([sujeto(['While', this]), verbo([has]), complemento([been, described, previously, it, has, never, been, demonstrated, via, remote, sensing, and, results, in, relative, stability, in, vegetation, vigour, inside, the, 'delta,', compared, to, that, outside])]). relacion([sujeto(['As', such, the, 'Delta']), verbo([acts]), complemento([as, a, regional, 'hydro-refugium'])]). relacion([sujeto(['This']), verbo([provides]), complemento(['insight,', not, only, to, the, potential, impact, of, future, climate, in, the, 'region,', but, also, demonstrates, why, similar, basins, are, attractive, to, 'fauna,', including, our, 'ancestors,', in, regions, like, eastern, 'Africa'])]). relacion([sujeto(['Although', vertebrate, evolution, operates, on, time, scales, longer, than, 'decades,', the, sensitivity, of, rift, wetlands, to, climate, change]), verbo([has]), complemento([been, stressed, by, some, 'authors,', and, this, work, demonstrates, another, example, of, the, unique, properties, that, such, basins, can, 'afford,', given, the, right, hydrological, conditions])]). relacion([sujeto(['Evidence']), verbo([suggests]), complemento([that, immunomodulatory, drugs, can, directly, act, on, glomerular, epithelial, cells, or, '\'', 'podocytes\',', the, cell, type, which, is, the, main, target, of, injury, in, 'MCN'])]). relacion([sujeto(['To', understand, the, nature, of, glucocorticoid, effects, on, 'non-immune', cell, 'functions,', we, generated, 'RNA', sequencing, data, from, human, podocyte, cell, lines, and, identified, the, genes, that, are, significantly]), verbo([regulated]), complemento([in, 'dexamethasone-treated', podocytes, compared, to, 'vehicle-treated', cells])]). relacion([sujeto(['Integrative', analysis, revealed, gene, networks, composed, of, critical, signaling, pathways, that, are, likely]), verbo([targeted]), complemento([by, dexamethasone, in, podocytes])]). relacion([sujeto(['In', 'locusts,', two, lobula, giant, movement, detector, neurons, '(', 'LGMDs)']), verbo([act]), complemento([as, looming, object, detectors])]). relacion([sujeto(['Reconstructions']), verbo([reveal]), complemento([that, many, 'trans-medullary-afferents', '(', 'TmAs)', connect, the, eye, with, each, 'LGMD,', one, 'TmA', per, facet, per, 'LGMD'])]). relacion([sujeto(['Since', any, lateral, interactions, between, 'LGMD', inputs]), verbo([have]), complemento([always, been, inhibitory, we, may, assume, these, reciprocal, lateral, connections, are, most, likely, inhibitory])]). relacion([sujeto(['Such', reciprocal, inhibitory, synapses]), verbo([increased]), complemento([the, 'LGMD\'s', selectivity, for, looming, over, passing, 'objects,', particularly, at, the, beginning, of, object, approach])]). relacion([sujeto(['The', activity, of, the, neuron, is, rebuilt, based, on, the, instantaneous, frequency, and, in, this, 'work,', we, use, the, first, layer, of, neurons, to, implement, image, segmentation, and, the, second, layer, of, neurons, to]), verbo([act]), complemento([as, visual, selector])]). relacion([sujeto(['MicroRNAs', '(', 'miRNAs)', may]), verbo([act]), complemento([as, either, tumor, suppressors, or, oncogenes, in, various, types, of, cancers])]). relacion([sujeto(['Previous', studies]), verbo([have]), complemento([indicated, that, 'miR-17-5p', is, involved, in, the, initiation, and, development, of, human, tumors])]). relacion([sujeto(['For', the, 'analysis,', we]), verbo([have]), complemento([established, a, stable, overexpression, or, depletion, of, 'miR-17-5p', 'NPC', cell, lines, for, analyzing, the, effects, of, cell, proliferation, by, 'MTT,', colony, 'formation,', and, cell, cycle, assay])]). relacion([sujeto(['Furthermore,', analysis, of, 2, '(', -, 'ΔΔCt)', value, in, 81, 'NPC', patients]), verbo([suggested]), complemento([that, the, elevated, expression, level, of, 'miR-17-5p', or, the, downregulated, expression, level, of, p21, was, significantly, correlated, with, tumor, size, '(', 'T', 'classification)', and, tumor, 'stage,', and, 'Kaplan-Meier', survival, analysis, revealed, a, correlation, between, 'miR-17-5p', or, p21, expression, level, and, overall, survival, times, in, 81, 'NPC', patients])]). relacion([sujeto(['MiR-17-5p']), verbo([promoted]), complemento([cell, growth, in, vivo, and, in, vitro, by, directly, targeting, p21])]). relacion([sujeto(['Our', results, indicate, that, 'miR-17-5p', can]), verbo([promote]), complemento([the, occurrence, of, 'NPC', and, it, may, serve, as, a, potential, novel, diagnostic, maker, or, therapeutic, target, for, 'NPC', in, the, future])]). relacion([sujeto(['This', 'cross-sectional,', observational, study, determined, the, prevalence, of, malnutrition, amongst, 189, adult, inpatients, in, a, teaching, hospital, using, the, 'Patient-Generated', 'Subjective', 'Global', 'Assessment', tool, and, compared, data, to, control, groups, for, coding, of, malnutrition, to, determine, the, estimated, unclaimed, financial, reimbursement]), verbo([associated]), complemento([with, this, comorbidity])]). relacion([sujeto(['Significant', associations, were]), verbo([found]), complemento([between, malnutrition, and, increasing, 'age,', decreasing, body, mass, 'index,', and, increased, length, of, stay])]). relacion([sujeto(['The', study]), verbo([found]), complemento([that, half, the, patients, were, 'malnourished,', with, older, adults, being, particularly, vulnerable])]). relacion([sujeto(['Dedicated', statistical, inference, approaches, are]), verbo([required]), complemento([to, understand, how, the, complex, interplay, of, these, processes, shapes, the, genetic, diversity, and, divergence, in, viral, populations])]). relacion([sujeto(['While', analyses, of, individual, patient, populations, lack, statistical, 'power,', we, detect, significant, evidence, for, an, abrupt, drop, in, 'non-synonymous', rates, in, late, stage, infection, and, a, more, gradual]), verbo([increase]), complemento([in, synonymous, rates, over, the, course, of, infection, in, a, joint, analysis, across, all, patients])]). relacion([sujeto(['The', former, is, predicted, by, the, immune, relaxation, hypothesis, while, the, latter, may, be, in, line, with]), verbo([increasing]), complemento([replicative, fitness, during, the, asymptomatic, stage])]). relacion([sujeto(['A', phylogeny]), verbo([has]), complemento([been, calculated, by, maximum, likelihood, comparisons, of, the, concatenated, consensus, protein, sequences, of, 29, tobamoviruses, shown, to, be, 'non-recombinant'])]). relacion([sujeto(['This', phylogeny]), verbo([has]), complemento([statistically, significant, support, 'throughout,', including, its, basal, branches])]). relacion([sujeto(['The', viruses, form, eight, lineages, that, are, congruent, with, the, taxonomy, of, the, hosts, from, which, each, was, first, isolated, 'and,', with, the, exception, of, three, of, the, 'twenty-nine', 'species,', all, fall, into, three, clusters, that]), verbo([have]), complemento([either, asterid, or, rosid, or, caryophyllid, hosts, '(', i])]). relacion([sujeto(['The', simplest, explanation, of, this, congruence, of, the, virus, and, host, phylogenies, is, that, most, tobamovirus, lineages]), verbo([have]), complemento(['co-diverged', with, their, primary, plant, hosts, for, more, than, 110, million, 'years,', and, only, the, 'brassica-infecting', lineage, originated, from, a, major, host, switch, from, asterids, to, rosids])]). relacion([sujeto(['Their', 'co-divergence', seems, to]), verbo([have]), complemento([been, '\'', 'fuzzy\'', rather, than, '\'', 'strict\',', permitting, viruses, to, switch, hosts, within, major, host, clades])]). relacion([sujeto(['Identifying', the]), verbo([cause]), complemento([of, a, criminal, 'act,', biological, or, 'otherwise,', does, not, necessarily, preclude, moral, or, legal, liability])]). relacion([sujeto(['The', first, prong, normatively, assesses, whether, a, defendant, meets, a, threshold, of, having, meaningfully, managed, his, risk, of, harming, others, based, on, what]), verbo([he]), complemento(['knew,', or, should, have, 'known,', about, his, own, proclivities, to, violence])]). relacion([sujeto(['A', defendant, is, criminally, responsible, for, his, action, only, if]), verbo([he]), complemento([is, shown, to, have, engaged, in, a, guilty, 'act-actus', reus, '(', eg, for, 'larceny,', voluntarily, taking, someone, 'else\'s', property, without, 'permission)-while', possessing, a, guilty, 'mind-mens', rea, '(', eg, knowing, that, he, had, taken, someone, 'else\'s', property, without, 'permission,', intending, not, to, return, 'it)-and', lacking, affirmative, defenses, '(', eg, the, insanity, defense, or, 'self-defense)'])]). relacion([sujeto(['But', there, is, no, reason, to, think, that, neuroscience, cannot]), verbo([provide]), complemento([evidence, that, will, challenge, our, understanding, of, criminal, responsibility])]). relacion([sujeto(['At', the, same, 'time,', some]), verbo([have]), complemento([argued, that, the, 'Americans', with, 'Disabilities', 'Act', protects, individuals, with, genetic, 'predispositions,', relying, on, a, label, akin, to, 'disability,', as, opposed, to, 'health,', to, characterize, this, group])]). relacion([sujeto(['Similarly,', courts]), verbo([have]), complemento([described, genetic, predisposition, as, a, disease, of, sorts, to, justify, insurance, payment, for, medical, intervention])]). relacion([sujeto(['Several', recent, articles]), verbo([have]), complemento([called, for, the, regulation, of, consumer, transcranial, direct, current, stimulation, '(', 'tDCS)', 'devices,', which, provide, low, levels, of, electrical, current, to, the, brain])]). relacion([sujeto(['However,', most, of, the, discussion, 'to-date']), verbo([has]), complemento([focused, on, ethical, or, normative, 'considerations;', there, has, been, a, notable, absence, of, scholarship, regarding, the, actual, legal, framework, in, the, 'United', 'States'])]). relacion([sujeto(['This', article, aims, to, fill, that, gap, by]), verbo([providing]), complemento([a, pragmatic, analysis, of, the, consumer, tDCS, market, and, relevant, laws, and, regulations])]). relacion([sujeto(['In', the, five, main, sections, of, this, 'manuscript,', 'I', take, into, account, '(', 'a)', the, history, of, the, 'do-it-yourself', tDCS, movement, and, the, subsequent, emergence, of, 'direct-to-consumer', 'devices;', '(', 'b)', the, statutory, language, of, the, 'Federal', 'Food,', 'Drug', and, 'Cosmetic', 'Act', and, how, the, definition, of, a, medical, 'device-which', focuses, on, the, intended, use, of, the, device, rather, than, its, mechanism, of, 'action-is', of, paramount, importance, for, discussions, of, consumer, tDCS, device, 'regulation;', '(', 'c)', how, both, the, 'Food', and, 'Drug', 'Administration', '(', 'FDA)', and, courts]), verbo([have]), complemento([understood, the, 'FDA\'s', jurisdiction, over, medical, devices, in, cases, where, the, meaning, of, '\'', intended, 'use\'', has, been, 'challenged;', '(', 'd)', an, analysis, of, consumer, tDCS, regulatory, enforcement, action, 'to-date;', and, '(', 'e)', the, multiple, 'US', 'authorities,', other, than, the, 'FDA,', that, can, regulate, consumer, brain, stimulation, devices])]). relacion([sujeto(['Taken', 'together,', this, paper, demonstrates, that, rather, than, a, '\'', regulatory, 'gap,\'', there, are, 'multiple,', distinct, pathways, by, which, consumer, tDCS, can, be]), verbo([regulated]), complemento([in, the, 'United', 'States'])]). relacion([sujeto(['Theory', of, 'mind,', especially, 'false-belief', 'understanding,']), verbo([has]), complemento([been, found, to, be, positively, correlated, with, both, 'EC', and, prosocial, orientation])]). relacion([sujeto(['The', combined, contribution, of, 'false-belief', understanding, and, language, to, explaining, the, relationship, between, 'EC', and, prosociality]), verbo([has]), complemento([yet, to, be, investigated])]). relacion([sujeto(['Thus,', in, the, current, 'study,', we, conducted, an, 'in-depth', exploration, of, how, 'preschoolers\'', 'false-belief', understanding, and, language, ability, each, contribute, to, modeling, the, relationship, between, 'children\'s', comprehension, of, emotion, and, their, disposition, to]), verbo([act]), complemento([prosocially, toward, 'others,', after, controlling, for, age, and, gender])]). relacion([sujeto(['Multiple', mediation, analysis, of, the, data]), verbo([suggested]), complemento([that, 'false-belief', understanding, and, language, ability, jointly, and, fully, mediated, the, effect, of, 'preschoolers\'', 'EC', on, their, prosocial, orientation])]). relacion([sujeto(['A', positive, 'genotype-phenotype', association, was]), verbo([found]), complemento([that, involves, the, 'multi-allelic', combination, of, three, risk, alleles, '(', one, in, 'PPARG', and, two, in, 'LYPLAL1)', with, obesity, and, overweight, '(', 'OR=3'])]). relacion([sujeto(['Our', data]), verbo([suggest]), complemento([the, joint, participation, of, 'PPARG-LYPLAL1', genes, in, metabolic, disorders, development])]). relacion([sujeto(['Hence,', these, genes, could]), verbo([act]), complemento([as, potential, biomarkers, in, obesity, and, overweight])]). relacion([sujeto(['Our', findings, underscore, the, complexity, of, metabolic, disorders, and]), verbo([provide]), complemento([evidence, about, the, importance, of, 'multi-loci', analysis, to, study, complex, diseases])]). relacion([sujeto(['This', article, briefly, explains, the, food, and, nutrition, implications, of, the, new, 'standards,', tax, penalties, and]), verbo([reporting]), complemento([requirements, for, 'non-profit', hospitals, and, healthcare, systems, to, maintain, a, 'tax-exempt', or, charitable, status, under, section, 501, '(', 'c)(3)', of, the, 'Federal', 'Internal', 'Revenue', 'Code', set, forth, in, 'The', 'Patient', 'Protection', and, 'Affordable', 'Care', 'Act', '(', 'P'])]). relacion([sujeto(['Unfortunately,', long, term, prospective, information, about, quality, of, life, and, outcomes, after, 'VHR']), verbo([has]), complemento([been, challenging, to, obtain])]). relacion([sujeto(['Decoupling', follow, up, from, clinical, visits, via, patient]), verbo([reported]), complemento([outcomes, '(', 'PROs)', has, been, proposed, as, a, means, of, achieving, better, long, term, assessments, after, 'VHR'])]). relacion([sujeto(['However,', the, modality, of, 'PRO', engagement, to, maximize, participation]), verbo([has]), complemento([not, been, well, established])]). relacion([sujeto(['A', formal, 'QI', initiative, was, undertaken, to, determine, if, long, term, 'PRO', follow, up, could, be]), verbo([increased]), complemento([at, a, single, 'AHSQC', site, by, adding, telephone, communication, to, email, communication, for, long, term, postoperative, 'VHR', assessment])]). relacion([sujeto(['Chromatin', plays, a, central, role, in]), verbo([maintaining]), complemento([hematopoietic, stem, cells, and, during, their, stepwise, differentiation])]). relacion([sujeto(['Although', a, large, number, of, histone, modifications, and, 'chromatin-modifying', enzymes]), verbo([have]), complemento([been, 'identified,', how, these, act, in, concert, to, produce, specific, phenotypic, outcomes, remains, to, be, established])]). relacion([sujeto(['MOZ', '(', 'KAT6A)', is, a, lysine, acetyltransferase, and]), verbo([enhances]), complemento([transcription, at, target, gene, loci])]). relacion([sujeto(['Despite', their, opposing, effects, on, 'transcription,', 'MOZ', and, 'BMI1']), verbo([regulate]), complemento([biological, systems, in, a, similar, manner])]). relacion([sujeto(['MOZ', and, 'BMI1', are]), verbo([required]), complemento([for, the, development, of, transplantable, 'HSCs,', for, restraining, cellular, 'senescence,', for, the, proper, patterning, of, the, 'anterior-posterior', axis, during, development, and, for, the, specification, and, maintenance, of, the, 'B-cell', lineage])]). relacion([sujeto(['We', recently, established, that, 'MOZ', and, 'BMI1']), verbo([have]), complemento([opposing, effects, on, the, initiation, of, 'Hox', gene, expression, during, embryonic, development, and, that, defects, in, body, segment, identity, specification, observed, in, single, 'Moz', and, 'Bmi1', mutants, were, rescued, in, compound, mutants])]). relacion([sujeto(['We']), verbo([report]), complemento([here, the, relationship, between, 'MOZ', and, 'BMI1', in, hematopoiesis])]). relacion([sujeto(['Using', 'Moz(+/-);Bmi1(+/-)', compound, mutant, 'mice,', we]), verbo([found]), complemento([that, 'MOZ', and, 'BMI1,', but, not, the, 'BMI1-related', protein, 'MEL18', '(', 'PCGF2),', play, synergistic, roles, in, maintaining, adult, 'HSCs'])]). relacion([sujeto(['Although', 'BMI1', restrains, premature, 'senescence,', we, established, that, 'MOZ']), verbo([acts]), complemento([to, maintain, the, quiescent, state, of, 'HSCs'])]). relacion([sujeto(['Our', work, revealed, that, 'MOZ', and, 'BMI1']), verbo([regulate]), complemento(['HSCs', in, a, synergistic, manner, by, acting, on, distinct, processes, required, to, maintain, 'HSCs'])]). relacion([sujeto(['Between', 2006, and, 2015, ',', the, 'Act', on, the, 'State', 'Emergency', 'Medical', 'System', was, the, key]), verbo([act]), complemento([governing, the, 'organization,', financing, and, provision, of, emergency, care, in, 'Poland'])]). relacion([sujeto(['The', critique, 'focused,', among, 'others,', on, the, lack, of, provisions, allowing, for, emergency, medical, services, '(', 'EMS)', to, be, performed, outside, the, 'EMS', 'units,', the, lack, of, a, separate, 'Act']), verbo([regulating]), complemento([the, profession, of, a, medical, rescuer, and, the, lack, of, a, separate, professional, organization, representing, medical, rescuers])]). relacion([sujeto(['However,', the, new, 'Act', did, not, meet, the, key, demands, of, medical, 'rescuers;', 'namely,', it, did, not, introduce, a, separate, legal]), verbo([act]), complemento([regulating, this, profession, nor, established, a, professional, organisation, representing, their, interests])]). relacion([sujeto(['An', analysis, of, the, vested, interests, of, various, groups, of, medical, professionals, indicates, that, these, interests, are, likely, to]), verbo([have]), complemento([influenced, the, final, legislative, outcome])]). relacion([sujeto(['Techniques', to, improve, solder, joint, reliability]), verbo([have]), complemento([been, the, recent, research, focus, in, the, electronic, packaging, industry])]). relacion([sujeto(['The', solder, matrix, hardness]), verbo([increased]), complemento([when, the, solder, matrix, was, 'refined,', but, decreased, when, the, solder, matrix, coarsened])]). relacion([sujeto(['The', interfacial, intermetallic, compound, '(', 'IMC)', layer, thickness, was]), verbo([found]), complemento([to, decrease, with, increasing, 'USV', 'time,', except, for, the, 'USV-treated', sample, with, 1.5, s])]). relacion([sujeto(['The', shear, strength, of, the, 'USV-treated', sample, with, 6, s, was, the, lowest, among, the, 'USV-treated', samples, due, to, the, formation, of, 'plate-like', 'Ag3Sn', that, may]), verbo([act]), complemento([as, the, crack, initiation, site])]). relacion([sujeto(['LFSCs', with, 'T2', hypointensity, were, more, likely, to]), verbo([require]), complemento([surgery, '(', p, =, 0.02, ')'])]). relacion([sujeto(['This', pooled, analysis, study, aimed, to]), verbo([reveal]), complemento([the, prognostic, relevance, of, microRNAs, '(', 'miRNAs)', in, patients, with, diffuse, large, 'B-cell', lymphoma, '(', 'DLBCL)'])]). relacion([sujeto(['We']), verbo([found]), complemento([significant, combined, 'HRs', for, poor, overall, survival, for, high, expression, of, 'miR-21', and, low, expression, of, 'miR-224', in, tumor, 'tissue,', but, for, favorable, relapse, free, survival, for, high, expression, of, 'miR-21', in, serum])]). relacion([sujeto(['MiRNAs', may]), verbo([act]), complemento([as, independent, prognostic, factors, in, patients, with, 'DLBCL,', and, useful, in, risk, stratification])]). relacion([sujeto(['Cases', with, positive, alcohol, readings]), verbo([found]), complemento([through, autopsy, or, toxicology, reports, were, retained, for, analysis])]). relacion([sujeto(['Alcohol', was, known, to, be]), verbo([involved]), complemento([in, 314, cases, '(', 40.8, '%', ')', ',', 279, recorded, a, positive, 'BAC,', 196, '(', 70.3, '%', ')', recorded, a, 'BAC', of, '≥0'])]). relacion([sujeto(['Known', alcohol, involvement, was]), verbo([found]), complemento([to, be, more, likely, for, victims, who, drowned, as, a, result, of, jumping, in, '(', 'χ(2)=7'])]). relacion([sujeto(['Although', prevention, is, 'challenging,', better, data, and, exposure, studies, are, the, next, step, to]), verbo([enhance]), complemento([prevention, efforts])]). relacion([sujeto(['Many', animal, studies]), verbo([have]), complemento([found, 'ZEA', to, possess, a, disruptive, effect, on, the, hormonal, 'balance,', mainly, due, to, its, similarity, to, 'naturally-occurring', estrogens])]). relacion([sujeto(['With']), verbo([increasing]), complemento([consciousness, of, the, adverse, effects, of, endocrine, disruptors, on, human, 'health,', it, is, becoming, more, important, to, monitor, 'ZEA', concentrations, in, food, and, identify, its, potential, effects, on, human, health])]). relacion([sujeto(['Based', on, a, review, of, recent, studies, on, animal, models, and, molecular, pathways, in, which, 'ZEA', is]), verbo([reported]), complemento([to, have, an, influence, on, 'humans,', we, postulate, that, 'ZEA', might, act, as, an, endocrine, disruptor, in, humans, in, a, similar, way, to, animals])]). relacion([sujeto(['Laterality', of, function, in, the, orofacial, musculature]), verbo([suggests]), complemento([there, may, be, 'side-to-side', asymmetry, of, proprioceptive, acuity, in, lip, movement, compared, to, the, temporomandibular, joint, '(', 'TMJ)'])]). relacion([sujeto(['Overall,', results, support]), verbo([enhanced]), complemento(['use-specific', proprioception])]). relacion([sujeto(['The', interaction, of, aminoacids, '(', 'Glycine,', 'Proline,', 'Lysine)', with, brushite, based, bone, cements]), verbo([has]), complemento([been, investigated, by, several, techniques, '(', 'FTIR', 'spectroscopy,', 'Thermogravimetry-TG,', 'Scanning', 'Electron', 'Microscopy-SEM,', mechanical, properties, 'studies),', with, the, aim, to, elucidate, the, properties, of, the, resulting, composite, materials, and, the, interaction, occurring, at, molecular, level, between, the, inorganic, matrix, and, the, organic, moieties])]). relacion([sujeto(['Focusing', on, 'Glycine', 'incorporation,', the, presence, of, a, fraction, of, bulk, 'Glycine,', weakly]), verbo([interacting]), complemento([with, the, inorganic, 'matrix,', together, with, 'Glycine', specifically, interacting, with, adsorption, sites, can, be, 'envisaged,', as, pointed, out, by, 'FT', 'IR', and, thermogravimetric, data])]). relacion([sujeto(['In', 'detail,', 'FT-IR', data, evidenced, changes, in, shape, and, position, of, bands]), verbo([associated]), complemento([to, stretching, modes, of, the, carboxylic, groups, in, 'Glycine', 'structure,', which, can, be, explained, by, the, coordination, of, these, functional, groups, with, the, 'Ca', ions, in, the, matrix])]). relacion([sujeto(['Due', to, the, coordination, with, 'Ca', ions, here, 'described,', 'Glycine', can]), verbo([act]), complemento([as, retardant, during, brushite, 'preparation,', allowing, good, workability, of, the, resulting, composite])]). relacion([sujeto(['The', growing, interest, in, the, use, of, recyclable, and, biodegradable, natural, materials]), verbo([has]), complemento([become, a, relevant, topic, in, pharmaceutics])]). relacion([sujeto(['In', this, 'work,', we]), verbo([suggest]), complemento([the, use, and, valorization, of, natural, horny, skeleton, of, marine, sponges, '(', 'Porifera,', 'Dictyoceratida)', as, 'bio-based', dressing, for, topical, drug, delivery])]). relacion([sujeto(['The', high, percentages, of, drug, are]), verbo([found]), complemento([after, absorption, into, sponge, powder, and, in, vitro, permeation, studies, demonstrate, that, cysteine, is, released, more, slowly, than, the, pure, drug, within, 1, h])]). relacion([sujeto(['Such', a, system, is, attractive, because, it, combines, the, known, healing, properties, of, cysteine, with, the, advantageous, potentials, of, the, 'collagen/proteoglycan', 'network,', which, can]), verbo([act]), complemento([as, biocompatible, carrier, able, to, absorb, the, excess, of, the, wound, exudate, while, releasing, the, drug])]). relacion([sujeto(['Furthermore,', due, to, its, glycosaminoglycans, 'content,', natural, sponge, skeletal, scaffold, might]), verbo([act]), complemento([as, 'bioactive-biomimetic', carrier, regulating, the, wound, healing, processes])]). relacion([sujeto(['New', generation, of, barrier, membranes]), verbo([has]), complemento([been, 'developed,', which, not, only, act, as, barriers, but, also, as, delivery, devices, to, release, specific, growth, factors])]). relacion([sujeto(['This', study, observed, biological, behaviors, of, bone, morrow, mesenchymal, stem, cells, '(', 'BMMSCs)', pretreated, by, bFGF, or, 'BMP-2', in, vitro, and, evaluated, differential, bone, regeneration, process]), verbo([induced]), complemento([by, bFGF, and, 'BMP-2', loaded, acellular, dermal, matrix, '(', 'ADM)', membrane, using, 'critical-size', rat, calvarial, defect, model, in, vivo])]). relacion([sujeto(['During', the, 'Pleistocene,', shifts, of, species, distributions, and, their, isolation, in, disjunct, refugia]), verbo([led]), complemento([to, varied, outcomes, in, how, taxa, diversified])]). relacion([sujeto(['We', isolated, 11, autosomal]), verbo([nuclear]), complemento([loci, and, one, mitochondrial, locus, from, a, total, of, 29, specimens, of, the, sister, species, 'pair,', 'Chestnut', 'Quail-thrush', 'Cinclosoma', castanotum, and, 'Copperback', 'Quail-thrush', 'C'])]). relacion([sujeto(['Gene', flow, between, the, species, since, divergence]), verbo([has]), complemento([been, low])]). relacion([sujeto(['The', analyses]), verbo([suggest]), complemento([the, effective, population, size, of, the, ancestor, was, 54, to, 178, times, smaller, than, populations, since, divergence])]). relacion([sujeto([clarum]), verbo([increased]), complemento([substantially, during, the, late, 'Pleistocene', and, continued, to, increase, through, the, 'Last', 'Glacial', 'Maximum', and, 'Holocene'])]). relacion([sujeto(['Our', results, contribute, to, awareness, of]), verbo([increased]), complemento([population, 'sizes,', following, significant, 'contractions,', as, having, been, important, in, shaping, diversity, in, 'Australian', arid, and, 'semi-arid', zones])]). relacion([sujeto(['Engaging', in, a, deeper, understanding, of, how, antipsychotics]), verbo([act]), complemento([on, the, brain, and, 'body,', at, the, 'cellular,', molecular, and, physiological, level, is, vital, to, comprehend, both, the, beneficial, and, potentially, harmful, actions, of, these, medications, and, stimulate, development, of, novel, therapeutics])]). relacion([sujeto(['Our', aim, is, to]), verbo([stimulate]), complemento([discussion, on, these, highly, clinically, relevant, topics, and, consider, how, we, might, use, current, and, evolving, knowledge, and, new, methodologies, in, the, fields, of, neuropharmacology, and, 'neuroscience,', to, advance, our, understanding, of, the, 'long-term', impact, of, antipsychotic, treatment])]). relacion([sujeto(['Its', function, is, the, subject, of, intensive, 'research,', not, least, because, of, the, possibility, that, it, could, be, used, in, therapeutic, strategies, to, reverse, hair, cell]), verbo([loss]), complemento([in, deafness])]). relacion([sujeto(['During', inner, ear, 'development,', 'Atoh1', is, only, able, to]), verbo([promote]), complemento([hair, cell, differentiation, at, specific, developmental, stages])]). relacion([sujeto(['Outside', the, 'ear,', 'Atoh1', is]), verbo([required]), complemento([for, differentiation, of, a, variety, of, other, cell, 'types,', for, example, in, the, intestine, and, cerebellum])]). relacion([sujeto(['So', 'far,', the, pathways, and, key, players, that, instruct, 'Atoh1', to]), verbo([act]), complemento([as, a, mechanosensory, cell, fate, determinant, in, the, context, of, the, inner, ear, are, largely, unknown])]). relacion([sujeto(['Here', we, review, evidence, that]), verbo([suggests]), complemento([that, 'Atoh1', function, in, hair, cell, differentiation, is, modulated, by, interaction, with, other, transcription, factors])]). relacion([sujeto(['Differences', in, water, availability, can]), verbo([cause]), complemento(['among-population', variation, in, ecological, processes, and, can, thus, interrupt, 'populations\'', connectivity, and, isolate, them, environmentally])]). relacion([sujeto(['Irano-Turanian', and, 'Saharo-Arabian', populations, had, higher, genetic, diversity, than, 'Mediterranean', 'populations,', and, genetic, diversity]), verbo([increased]), complemento([significantly, with, increasing, temperature])]). relacion([sujeto(['Genetic', diversity, in, 'Salvia', syriaca, was, affected, by, population, 'size,', while, genetic, diversity]), verbo([responded]), complemento([to, drought, in, 'S'])]). relacion([sujeto(['For', both, 'species,', high, levels, of, genetic, differentiation, were]), verbo([found]), complemento([as, well, as, two, 'well-supported', phytogeographical, groups, of, 'populations,', with, 'Mediterranean', populations, clustering, in, one, group, and, the, 'Irano-Turanian', and, 'Saharo-Arabian', populations, in, another])]). relacion([sujeto(['We', conclude, that, environmental, heterogeneity, may]), verbo([act]), complemento([as, driver, for, the, observed, variation, in, genetic, diversity])]). relacion([sujeto(['Emerging', evidence]), verbo([suggests]), complemento([that, small, nucleolar, 'RNAs', '(', 'snoRNAs)', and, their, host, genes, '(', 'SNHGs)', have, malfunctioning, roles, in, the, development, of, human, cancers])]). relacion([sujeto(['We', globally, investigated, the, molecular, mechanisms, by, which, snoRNA, host, gene, 6, '(', 'SNHG6)']), verbo([promotes]), complemento([hepatocellular, carcinoma, '(', 'HCC)', progression, using, human, tissues, and, cell, lines])]). relacion([sujeto(['We']), verbo([found]), complemento([that, 'SNHG6', is, overexpressed, in, 'HCC', tissues, and, in, hepatoma, cell, lines, and, is, closely, associated, with, histologic, 'grade,', hepatitis, 'B', virus, 'DNA,', 'Barcelona', 'Clinic', 'Liver', 'Cancer', stage, and, portal, vein, tumor, thrombus, in, patients, with, 'HCC'])]). relacion([sujeto(['Knockdown', of, 'SNHG6']), verbo([induced]), complemento([apoptosis, and, repressed, cell, cycle, progression, in, hepatoma, cell, 'lines,', whereas, transgenic, expression, of, 'SNHG6', in, the, immortalized, human, hepatic, cell, line, 'L02', had, opposite, effects])]). relacion([sujeto(['SNHG6', may]), verbo([act]), complemento([as, a, competing, endogenous, 'RNA,', effectively, becoming, a, sink, for, 'miR-101-3p', and, thereby, modulating, the, derepression, of, zinc, finger, 'E-box', binding, homeobox, 1, ',', imposing, an, additional, level, of, 'post-transcriptional', regulation])]). relacion([sujeto(['Functionally,', 'SNHG6']), verbo([promotes]), complemento([tumor, growth, and, metastasis, by, inducing, epithelial, to, mesenchymal, transition])]). relacion([sujeto(['Further', investigations, showed, that, 'SNHG6', could, affect, 'HCC', tumorigenesis, by]), verbo([binding]), complemento([to, 'up-frameshift', protein, 1, and, regulating, 'Smad7', expression])]). relacion([sujeto(['Human', milk, contains, growth, factors, that]), verbo([maintain]), complemento([intestinal, mucosal, 'homeostasis,', but, the, molecular, mechanisms, behind, how, these, growth, factors, regulate, gene, transcription, are, largely, unknown])]). relacion([sujeto(['In', this, 'study,', 'IEC-6', '(', rat, intestinal, epithelial, 'cells)', cells, were, used, as, a, model, to, study, cell, differentiation]), verbo([mediated]), complemento([by, transforming, growth, 'factor-β2', '(', 'TGF-β2),', the, most, abundant, growth, factor, in, human, milk])]). relacion([sujeto(['We', focused, on, the, transcription, factor, early, growth, 'response-1', '(', 'EGR-1),', as, we]), verbo([found]), complemento([a, robust, and, rapid, response, in, our, initial, transcription, factor, screen])]). relacion([sujeto(['Chromatin', immunoprecipitation, sequencing, was, performed, to, map, 'genome-wide', 'EGR-1']), verbo([binding]), complemento([sites, on, more, than, 1800, 'genes,', widely, involved, in, processes, such, as, gene, 'expression,', 'transcription,', membrane, invagination, and, metabolism])]). relacion([sujeto(['In', 'particular,', more, than, 15, 'Wnt', signaling, pathway, genes]), verbo([have]), complemento(['EGR-1', binding, 'sites;', among, 'them,', 'Axin1', was, the, limiting, 'factor,', ensuring, proper, 'β-catenin', accumulation, in, the, cytoplasm])]). relacion([sujeto(['We', further, used, chromatin, immunoprecipitation, quantitative, 'PCR', to, validate, that, 'EGR-1']), verbo([binds]), complemento([to, the, region, of, -, 636, /, -, 454, bp, and, -, 454, /, -, 200, bp, of, the, 'Axin1', promoter, and, functionally, activates, gene, expression])]). relacion([sujeto(['The', effect, of, 'TGF-β2', on]), verbo([maintaining]), complemento([small, intestinal, cell, homeostasis, was, partially, explained, by, 'Axin1', activation, through, 'EGR-1'])]). relacion([sujeto(['PCC', 6803, ',', transcription, of, petE, and, petJ, is]), verbo([activated]), complemento([and, 'repressed,', 'respectively,', by, 'Cu'])]). relacion([sujeto(['Here,', we, show, that, 'Ni', can]), verbo([act]), complemento([similarly, to, 'Cu', in, inducing, petE, and, repressing, 'petJ,', thus, leading, to, a, partial, switch, between, cytochrome, c6, and, plastocyanin])]). relacion([sujeto(['Transcription', of, these, genes, is, only, altered, by, 'Ni', in, 'Cu-depleted', 'medium,', and, none, of, the, 'Ni-dependent', transcription, factors, described, in, 'Synechocystis,', 'NrsR', and, 'InrS', seem, to, be]), verbo([involved]), complemento([in, this, regulation])]). relacion([sujeto(['Electrospun', mats, containing, cyclodextrin, polymers, '(', 'poly-αCD', or, 'poly-βCD)', were, developed, to]), verbo([act]), complemento([as, wound, dressings, showing, tunable, release, rate, of, the, antifungal, agent, fluconazole, incorporated, forming, inclusion, complexes])]). relacion([sujeto(['Mats', were, coated, by, hexamethyldisiloxane, '(', 'HMDSO)', plasma, polymerization, to, create, a, hydrophobic, layer, that]), verbo([prevented]), complemento([rapid, drug, diffusion])]). relacion([sujeto(['HMDSO', coating, was, evidenced, by, the, 'Si', content, of, mat, surface, '(', 'EDX', 'analysis)', and, by, the]), verbo([increase]), complemento([in, the, water, contact, angle, '(', up, to, 130, °, ')'])]). relacion([sujeto(['In', 'physiological-mimicking', 'medium,', 'non-treated', mats, showed, burst]), verbo([release]), complemento([of, 'fluconazole,', whereas, 'HMDSO-coated', mats, sustained, the, release, and, delayed, disintegration, of, 'PVP-based', mats])]). relacion([sujeto(['Antifungal', tests, evidenced, that, both, coated, and, 'non-coated', mats, efficiently]), verbo([inhibited]), complemento([the, growth, of, 'Candida', albicans])]). relacion([sujeto(['Unexpected', presentation, of, a, startling, auditory, stimulus, '(', 'SAS>120', 'decibels)', in, a, reaction, time, '(', 'RT)', paradigm, results, in, the, startle, reflex, and, an, early]), verbo([release]), complemento(['(', &, 'lt;100ms)', of, the, preplanned, motor, response, '(', 'StartReact', 'effect)'])]). relacion([sujeto(['Mechanical', perturbations, applied, to, the, upper, limbs, elicit, 'short-', '(', 'M1)', and, 'long-latency', '(', 'M2)', stretch, reflexes, and]), verbo([have]), complemento([also, been, shown, to, initiate, intended, motor, responses, early, '(', &, 'lt;100ms)'])]). relacion([sujeto(['(', 2013, ')', recently, proposed, that, unexpected, delivery, of, a, perturbation, could, also, elicit, a, startle, response, and, therefore, the, 'StartReact', effect, may, be, responsible, for, the, early]), verbo([trigger]), complemento([of, a, preplanned, response])]). relacion([sujeto(['Our', findings]), verbo([suggest]), complemento([that, while, unexpected, upper, limb, perturbations, can, be, 'startling,', startle, triggering, of, the, preplanned, voluntary, response, is, not, the, primary, mechanism, responsible, for, 'goal-dependent', modulation, of, the, 'M2', response])]). relacion([sujeto(['SSC']), verbo([ensures]), complemento([that, contextual, groupings, of, goal, or, 'motor-relevant', representations, will, demonstrate, continuous, activity, over, a, delay, period])]). relacion([sujeto(['The', nodes, that, demonstrate, 'SSC', are, a, subset, of, the, active, representations, from, the, previous, 'state,', and, can]), verbo([act]), complemento([as, referents, to, which, newly, introduced, representations, of, succeeding, states, relate])]). relacion([sujeto(['Coactive', nodes, pool, their, spreading, 'activity,', converging, on, and]), verbo([activating]), complemento([new, 'nodes,', adding, these, to, the, remaining, nodes, from, the, previous, state])]). relacion([sujeto(['Because', a, number, of]), verbo([associated]), complemento([representations, can, be, sustained, 'continuously,', each, brain, state, is, embedded, recursively, in, the, previous, 'state,', amounting, to, an, iterative, process, that, can, implement, learned, algorithms, to, progress, toward, a, complex, result])]). relacion([sujeto(['Included', is, a, discussion, of, the, implications, that, 'SSC', and, icSSC, may]), verbo([have]), complemento([for, understanding, working, 'memory,', defining, 'consciousness,', and, constructing, 'AI', architectures])]). relacion([sujeto(['One', way, to, improve, 'PM', performance, is, to]), verbo([increase]), complemento([the, salience, of, a, cue, announcing, that, it, is, time, to, act])]). relacion([sujeto(['Multiple', sclerosis, '(', 'MS)', patients, often]), verbo([report]), complemento(['PM', failures, and, there, is, growing, evidence, of, 'PM', deficits, among, this, population])]). relacion([sujeto(['Thirty-nine', '(', 39, ')', 'MS', patients, were, compared, to, 18, healthy, controls, on, a, 'PM', task]), verbo([modulating]), complemento([cue, salience, during, an, ongoing, general, knowledge, test])]). relacion([sujeto(['Interestingly,', 'low-', and, 'high-executive', 'patients\'', performance, differed, when, the, cue, was, not, 'salient,', but, not, when, it, 'was,']), verbo([suggesting]), complemento([that, 'low-executive', 'MS', patients, benefited, more, from, cue, salience])]). relacion([sujeto(['In', 'amphibians,', 'DDE', was]), verbo([found]), complemento([to, act, as, antiandrogenic, endocrine, disrupting, chemical, '(', 'EDC),', whereas, in, other, species, 'DDE', was, found, to, act, as, an, estrogen])]). relacion([sujeto(['Lowered', sexual, arousal, of, exposed, males, was, indicated, by, a]), verbo([decreased]), complemento([production, of, advertisement, calls, and, higher, amounts, of, calls, that, suggest, a, sexually, unaroused, state, of, the, males])]). relacion([sujeto(['Our', results, further, indicate, that, 'DDE', can, display, 'both,', estrogenic, and, antiandrogenic, 'MOA,', either, of, which, can]), verbo([have]), complemento([adverse, effects, on, reproductive, physiology, and, behavior, in, 'X'])]). relacion([sujeto(['Social', marketing, managers]), verbo([promote]), complemento([desired, behaviors, to, the, audience, by, tangibilizing, them, in, the, form, of, environmental, opportunities, in, order, to, enhance, benefits, and, reduce, barriers])]). relacion([sujeto(['This', study, proposed, &, 'quot;benchmarks"', modified, from, those]), verbo([found]), complemento([in, the, past, literature, that, would, match, important, concepts, of, the, social, marketing, framework, and, whose, inclusion, would, ensure, behavior, change, effectiveness, as, well, as, analyzed, behavior, change, interventions, on, a, &, 'quot;social', marketing, 'continuum"', to, assess, whether, the, number, of, benchmarks, and, the, role, of, specific, benchmarks, influence, the, effectiveness, of, physical, activity, promotion, efforts])]). relacion([sujeto(['Findings', based, on, 'chi-square,', 'Mallow\'s', 'Cp,', and, 'Logical', 'Analysis', of, 'Data', tests, revealed, that, the, presence, of, more, benchmarks, in, interventions]), verbo([increased]), complemento([the, likelihood, of, success, in, promoting, physical, activity])]). relacion([sujeto(['Social', marketing, is, an, effective, approach, in]), verbo([promoting]), complemento([physical, activity, among, adults, when, a, substantial, number, of, benchmarks, are, employed, and, when, managers, understand, the, 'audience,', make, the, desired, behavior, 'tangible,', and, promote, the, desired, behavior, persuasively])]). relacion([sujeto(['Obesity', is]), verbo([associated]), complemento([with, arterial, stiffening, and, diminished, quality, of, life])]). relacion([sujeto(['After', the, 'intervention,', 'brachial-ankle', pulse, wave, velocity]), verbo([decreased]), complemento(['(', 'p<0'])]). relacion([sujeto([1, ')', were]), verbo([associated]), complemento([with, 'MVPA,', while, factors, such, as, 'BMI', '(', 'p<'])]). relacion([sujeto([1, ')', were]), verbo([associated]), complemento([with, screen, time])]). relacion([sujeto([1, ')', and, sociability, were]), verbo([associated]), complemento([with, 'MVPA,', however, factors, such, as, 'BMI', '(', 'p<'])]). relacion([sujeto([5, ')', were, more, closely]), verbo([associated]), complemento([with, screen, time])]). relacion([sujeto(['Social', factors, were, more, closely]), verbo([associated]), complemento([with, 'MVPA,', while, individual, factors, were, significantly, correlated, with, screen, time, for, both, boys, and, girls])]). relacion([sujeto(['Correlates', differed, for, boys, and, 'girls,']), verbo([suggesting]), complemento([that, interventions, should, consider, both, the, target, population, as, well, as, the, activity, behavior])]). relacion([sujeto(['Older', adults, with, osteoarthritis, '(', 'OA)', often]), verbo([report]), complemento([that, their, disease, symptoms, are, exacerbated, by, weather, conditions])]). relacion([sujeto(['This', study, examines, the, association, between, outdoor, physical, activity, '(', 'PA)', and, weather, conditions, in, older, adults, from, six, 'European', countries, and, assesses, whether, outdoor, 'PA', and, weather, conditions, are, more, strongly]), verbo([associated]), complemento([in, older, persons, with, 'OA', than, in, those, without, the, condition])]). relacion([sujeto([1, ')', were]), verbo([associated]), complemento([with, 'PA'])]). relacion([sujeto(['Temperature', was, more, strongly]), verbo([associated]), complemento([with, 'PA', in, participants, without, 'OA', '(', 'B=1'])]). relacion([sujeto(['Weather', conditions, are]), verbo([associated]), complemento([with, outdoor, 'PA', in, older, adults, in, the, general, population])]). relacion([sujeto(['Outdoor', 'PA', and, weather, conditions, were, more, strongly]), verbo([associated]), complemento([in, older, adults, without, 'OA', than, in, their, counterparts, with, 'OA'])]). relacion([sujeto(['An', intervention, effect, was]), verbo([found]), complemento([by, increasing, the, weekly, time, in, 'MVPA', '(', effect, 'size=0'])]). relacion([sujeto(['The', intervention, was, effective, in]), verbo([promoting]), complemento([improvements, in, some, 'PA', 'outcomes,', but, the, changes, were, not, sufficient, to, increase, the, proportion, of, those, meeting, 'PA', recommendations])]). relacion([sujeto(['Exposure', to, green, space]), verbo([has]), complemento([been, associated, with, increased, physical, activity])]). relacion([sujeto(['Our', objective, was, to, determine, whether, exposure, to, green, space, was]), verbo([associated]), complemento([with, physical, activity, in, pregnant, women])]). relacion([sujeto(['Exposure', to, green, space, was, not]), verbo([associated]), complemento([with, participation, in, physical, activity, during, first, trimester, and, the, remainder, of, pregnancy, once, preference, for, living, in, greener, neighborhoods, was, taken, into, account])]). relacion([sujeto(['The', lack, of, association, between, green, space, and, physical, activity]), verbo([found]), complemento([in, this, study, does, not, necessarily, mean, that, living, in, green, space, will, not, translate, into, better, pregnancy, health])]). relacion([sujeto(['Transit-related', walking]), verbo([provides]), complemento([a, potential, opportunity, to, promote, general, walking, 'behavior,', yet, few, studies, have, examined, this, issue])]). relacion([sujeto(['This', study, illustrated, several, implications, regarding, to, 'transit-related', 'walking,', such, as, creating, short, 'home-transit', distances, and]), verbo([targeting]), complemento([whites, in, promoting, 'transit-related', walking])]). relacion([sujeto(['Apps', may, not]), verbo([have]), complemento([sufficient, accuracy, to, monitor, important, physical, parameters, of, human, body, movement])]). relacion([sujeto(['Apps', need, to, be, developed, that, 'can,', in, 'particular,']), verbo([respond]), complemento([differently, based, on, a, 'person\'s', weight, status])]). relacion([sujeto(['Numerous', studies]), verbo([have]), complemento([focused, on, the, role, of, environments, in, promoting, physical, 'activity,', but, few, studies, have, examined, the, specific, locations, where, children, are, active, and, whether, being, active, in, these, locations, is, associated, with, physical, activity, levels, over, time])]). relacion([sujeto(['Latent', transition, analyses, were, used, to, characterize, how, these, latent, classes, change, over, time, and, to, determine, whether, the, latent, transitions, were]), verbo([associated]), complemento([with, changes, in, physical, activity, levels])]). relacion([sujeto(['Most', children]), verbo([maintained]), complemento([their, latent, status, over, time])]). relacion([sujeto(['Physical', activity, levels, declined, for, all, 'groups,', but, significantly, less, so, for, children, who]), verbo([maintained]), complemento([their, membership, in, the, '\'', greater, 'variety\'', latent, status])]). relacion([sujeto(['Physical', inactivity, in, midlife, women, is]), verbo([associated]), complemento([with, increased, 'intra-abdominal', adipose, tissue, development])]). relacion([sujeto(['The', first, 2, groups, 'identified,', pilot, 'tested,', and, then, ranked, activities, for, their, ability, to]), verbo([promote]), complemento([sustained, 'PA'])]). relacion([sujeto(['Consensus', was, reached, regarding, activities, that, could, be, valuable, in]), verbo([promoting]), complemento([sustained, 'PA', in, midlife, women])]). relacion([sujeto(['A', sample, of, 1141, adolescents, as, well, as, their, parents]), verbo([participated]), complemento([in, this, survey])]). relacion([sujeto(['The', likelihood, for, an, adolescent, to, exceed, 2, hours, of, screen, time, is, 3.87, times, more, when]), verbo([he]), complemento([has, his, meals, in, front, of, a, 'TV', screen, on, a, daily, 'basis,', 1.69, times, more, when, the, 'TV', is, 'on,', often, as, not, on, his, return, from, school, and, 1.74, times, more, when, there, is, a, 'PC', in, the, 'adolescent\'s', bedroom])]). relacion([sujeto(['Plant', 'Pleiotropic', 'Drug', 'Resistance', '(', 'PDR)-type', 'ABC', transporters, are, known, secondary, metabolite, 'transporters,', and, several]), verbo([have]), complemento([been, implicated, in, pathogen, or, herbivore, defense])]). relacion([sujeto(['Here,', we]), verbo([report]), complemento([on, 'Petunia', hybrida, 'PhPDR2', as, a, major, contributor, to, 'trichome-related', chemical, defense])]). relacion([sujeto(['PhPDR2', was]), verbo([found]), complemento([to, localize, to, the, plasma, membrane, and, be, predominantly, expressed, in, multicellular, glandular, trichomes, of, leaves, and, stems])]). relacion([sujeto(['Untargeted', screening, of, pdr2, trichome, metabolite, contents, showed, a, significant]), verbo([decrease]), complemento([in, petuniasterone, and, petuniolide, 'content,', 'compounds,', which, had, previously, been, shown, to, act, as, potent, toxins, against, various, insects])]). relacion([sujeto(['Our', findings]), verbo([suggest]), complemento([that, 'PhPDR2', plays, a, leading, role, in, controlling, petuniasterone, levels, in, leaves, and, trichomes, of, 'petunia,', thus, contributing, to, herbivory, resistance])]). relacion([sujeto(['High', 'PA/low', sitting, did, not, attenuate, the, risk, of, 'T2DM']), verbo([associated]), complemento([with, 'overweight/obesity'])]). relacion([sujeto(['A', 29, -, item, questionnaire, was, administered, at, five, health, and, wellness, sites]), verbo([targeting]), complemento([low, income, communities, in, 'Chicago'])]). relacion([sujeto(['A', total, of, 291, individuals]), verbo([participated]), complemento([and, were, predominantly, female, '(', 69.0, '%', ')'])]). relacion([sujeto(['Majority']), verbo([reported]), complemento([incomes, less, than, '$30,000', '(', 72.9, '%', ')', and, identified, as, 'African', 'American/Black/Caribbean', '(', 49.3, '%', ')', or, 'Mexican/Mexican', 'American', '(', 34.3, '%', ')'])]). relacion([sujeto(['Free', 'Internet-based', exercise, programs, were, the, most, preferred, method, to]), verbo([increase]), complemento(['PA', levels, '(', 31.6, '%', ')', ',', while, some, respondents, '(', 21.0, '%', ')', thought, none, of, the, surveyed, technology, applications, would, help])]). relacion([sujeto(['Technology', preferences, to]), verbo([increase]), complemento(['PA', levels, 'varied,', with, a, considerable, number, of, respondents, not, preferring, the, surveyed, technology, platforms])]). relacion([sujeto(['Creating', educational, opportunities, to]), verbo([increase]), complemento([awareness, may, maximize, the, effectiveness, of, 'technology-based', 'PA', interventions])]). relacion([sujeto(['This', could]), verbo([suggest]), complemento([that, adolescent, girls, may, not, walk, enough, to, stratify, health, and, health, related, outcomes, and, as, a, result, the, data, could, not, be, used, to, inform, an, appropriate, step, guideline, for, this, population])]). relacion([sujeto(['After', adjusting, for, potential, 'confounders,', perceived, higher, residential, 'density,', 'GIS-measured', higher, population, 'density,', better, access, to, 'destinations,', better, access, to, public, 'transport,', longer, sidewalk, 'length,', and, higher, street, 'connectivity,', were]), verbo([associated]), complemento([significantly, with, lower, sitting, time, for, transport])]). relacion([sujeto(['Residents', living, in, neighborhoods, with, attributes, previously]), verbo([found]), complemento([to, be, associated, with, more, walking, tended, to, spend, less, time, sitting, for, transport, during, 'leisure-time'])]). relacion([sujeto(['The', health, benefits, of, 'walkability-related', attributes, may, accrue, not, only, through]), verbo([increased]), complemento([physical, 'activity,', but, also, through, less, sedentary, time])]). relacion([sujeto(['A', better, cardiovascular, risk, profile, as, well, as, receiving, physical, activity, advice, or, weight]), verbo([loss]), complemento([advice, was, associated, with, better, physical, activity, levels])]). relacion([sujeto(['The', physical, activity, status, improved, significantly, over, 'time,', the, proportion, of, patients]), verbo([reporting]), complemento([vigorous, physical, activity, for, at, least, 20, minutes, '≥', 3, 'times/week', increased, from, 14.1, '%', to, 20.2, '%', '(', 'p<0'])]). relacion([sujeto(['Although', an]), verbo([increase]), complemento([was, seen, in, the, proportion, of, patients, being, adequately, physical, 'active,', physical, activity, levels, remain, suboptimal, in, many, 'CHD', patients])]). relacion([sujeto(['Promoting']), verbo([regular]), complemento([physical, activity, '(', 'PA)', and, lessening, sedentary, behaviors, '(', 'SB)', constitute, a, public, health, priority])]). relacion([sujeto(['Recent', evidence]), verbo([suggests]), complemento([that, 'PA', and, 'SB', are, not, only, related, to, reflective, processes, '(', e])]). relacion([sujeto(['IAAT', towards, 'PA']), verbo([decreased]), complemento([in, the, 'ApSB-AvPA', 'condition,', tended, to, increase, in, the, 'ApPA-AvSB', 'condition,', and, remained, stable, in, the, control, condition])]). relacion([sujeto(['Most', 'importantly,', the, 'ApPA-AvSB', manipulation]), verbo([led]), complemento([to, more, time, spent, exercising, than, the, 'ApSB-AvPA', condition])]). relacion([sujeto(['These', findings]), verbo([provide]), complemento([preliminary, evidence, that, a, single, intervention, session, can, successfully, change, impulsive, approach, tendencies, towards, 'PA', and, can, increase, the, time, devoted, to, an, exercise, 'task,', especially, among, individuals, who, need, to, be, more, physically, active])]). relacion([sujeto(['The', purpose, of, this, study, was, to, examine, changes, in, physical, activity, and, healthy, eating, knowledge, and, behaviors]), verbo([associated]), complemento([with, the, level, of, exposure, to, 'POWERPLAY,', a, 'men-centered', workplace, health, promotion, program])]). relacion([sujeto(['Compared', to, the, low, exposure, 'group,', those]), verbo([reporting]), complemento([high, exposure, scored, significantly, higher, on, physical, activity, knowledge, '(', 'F', '(', 1, ',', 99, ')', =, 14.17, ',', p, &, 'lt;'])]). relacion([sujeto(['The', high, exposure, group, also]), verbo([reported]), complemento([significantly, more, minutes, walked, place, to, place, '(', 'F', '(', 2, ',', 206, ')', =, 3.91, ',', p, =])]). relacion([sujeto(['POWERPLAY', shows, significant, promise, as, a, workplace, health, promotion, approach, and, may]), verbo([have]), complemento([an, even, greater, impact, when, program, exposure, is, augmented, with, environmental, and, policy, changes])]). relacion([sujeto(['School', districts, in, the, 'United', 'States', are, turning, towards, new, sources, of, revenue, to]), verbo([maintain]), complemento([their, interscholastic, sports, programs])]). relacion([sujeto(['We', also]), verbo([found]), complemento([that, participation, fees, are, not, decreasing, the, number, of, sport, opportunities, for, 'students,', participation, opportunities, are, higher, in, schools, with, 'fees;', but, participation, rates, are, similar, between, schools, with, and, without, participation, fees])]). relacion([sujeto(['Harmful', health, effects]), verbo([associated]), complemento([with, sedentary, behaviour, may, be, attenuated, by, breaking, up, long, periods, of, sitting, by, standing, or, walking])]). relacion([sujeto(['It']), verbo([has]), complemento([not, previously, been, described, how, the, definition, of, minimum, break, duration, affects, sitting, outcomes])]). relacion([sujeto(['Absolute', numbers, of, 'sit-to-stand', transitions, 'decreased,', and, number, of, prolonged, sitting, periods, and, total, time, accumulated, in, prolonged, sitting, periods, 'increased,', with]), verbo([increasing]), complemento([minimum, break, length])]). relacion([sujeto(['Perceived', neighborhood, safety, for, walking, and, biking, was]), verbo([associated]), complemento([with, greater, 'ACS', among, boys, '(', 'p-value=0'])]). relacion([sujeto(['In', this, first, known, assessment, of, 'community-based', prevalence, and]), verbo([associated]), complemento([risk, factors, in, 'Timor-Leste,', soil, transmitted, helminth, infections, were, highly, 'prevalent,', indicating, a, need, for, soil, transmitted, helminth, control])]). relacion([sujeto(['PDRG1,', is, short, for, 'P53', and, 'DNA', 'damage-regulated', 'gene,', which]), verbo([have]), complemento([been, found, over, 10, years])]). relacion([sujeto(['Although', severe, studies]), verbo([have]), complemento([described, the, roles, of, 'PDRG1', separately, in, many, kinds, of, 'tumors,', how, to, act, as, an, oncogene, are, unclear])]). relacion([sujeto(['Another', interesting]), verbo([finding]), complemento([is, 'PDRG1', could, promote, radioresistance, involved, the, 'ATM-p53', signaling, pathway, in, lung, cancer])]). relacion([sujeto(['This', is, accomplished, through, 'contact-dependent', and, -, independent, mechanisms, that]), verbo([involve]), complemento([crosstalk, between, 'Treg', cells, and, other, immune, and, 'tissue-specific', cell, types])]). relacion([sujeto(['The', same, machinery, is, employed, by, 'Tregs', to]), verbo([regulate]), complemento([immune, responses, to, 'cancer,', limiting, both, 'pro-tumor', inflammation, and, 'anti-tumor', immunity])]). relacion([sujeto(['Factors', produced, by, 'Treg', cells, also]), verbo([act]), complemento([directly, on, transformed, epithelial, cells, and, exert, opposing, effects, during, different, stages, of, cancer, development])]). relacion([sujeto(['Reduced', mitochondrial, function, is, an, important]), verbo([cause]), complemento([of, aging, and, 'age-related', diseases])]). relacion([sujeto(['To', address, these, 'issues,', we]), verbo([recruited]), complemento([60, longevity, families, consisting, of, 206, family, members, '(', cohort, 1, ')', and, explored, their, mtDNA, copy, number])]). relacion([sujeto(['In', 'addition,', we]), verbo([found]), complemento([a, positive, association, of, mtDNA, copy, number, in, centenarians, with, that, in, 'F1', offspring, '(', 'r =', 0.54, ',', 'p =', 0.0008, ')', but, not, with, that, in, 'F1', spouses])]). relacion([sujeto(['RNA', sequencing, analysis]), verbo([suggests]), complemento([that, the, 'single-stranded', 'DNA-binding', protein, 4, was, significantly, associated, with, mtDNA, copy, number, and, was, highly, expressed, in, centenarians, as, well, as, 'F1', offspring, versus, the, 'F1', 'spouses,', thus, likely, regulates, the, mtDNA, copy, number, in, the, 'long-lived', family, members])]). relacion([sujeto(['In', 'conclusion,', our, results]), verbo([suggest]), complemento([that, the, pattern, of, high, mtDNA, copy, number, is, likely, 'inheritable,', which, may, act, as, a, favorable, factor, to, familial, longevity, through, assuring, adequate, energy, supply])]). relacion([sujeto(['New', drug, candidates, for, 'Alzheimer\'s', disease, in, patients, with, androgen, deficiency, should, ideally, be, able, to]), verbo([act]), complemento([not, only, on, multiple, brain, targets, but, also, to, correct, impaired, endocrine, functions, in, hypogonadal, men, with, 'Alzheimer\'s', disease])]). relacion([sujeto(['Ropren(®)', alone, or, in, combination, with, 'TP-induced', anxiolytic, effects, as, evidenced, in, the, 'EPM', and, in, the, 'LDT', and]), verbo([increased]), complemento([locomotor, activity, in, the, 'OFT'])]). relacion([sujeto(['Additionally,', it, was, observed, that, dopamine, '(', 'DA)', and, serotonin, '(', 5, -, 'HT)', levels]), verbo([increased]), complemento([while, 5, -, hydroxyindoleacetic, acid, '(', 5, -, 'HIAA)/5-HT', ratio, in, the, hippocampus, decreased])]). relacion([sujeto(['Our', results, indicate, that, 'Ropren(®)']), verbo([has]), complemento([a, marked, 'anxiolytic-like', action, due, to, an, increase, in, the, monoamines, levels, in, the, experimental, rat, model, of, 'Alzheimer\'s', disease, with, altered, levels, of, androgens])]). relacion([sujeto(['HBV', infection]), verbo([has]), complemento([been, reported, to, be, closely, associated, with, 'HCC', 'development;', 'however,', the, underlying, mechanisms, are, unclear])]). relacion([sujeto(['Emerging', evidence]), verbo([has]), complemento([indicated, that, long, 'non-coding', 'RNAs', '(', 'lncRNAs)', play, important, regulatory, roles, in, the, pathogenesis, and, progression, of, cancers])]). relacion([sujeto(['We', identified, a, novel, 'lncRNA,', 'lncRNA-Unigene56159,', which, is, highly]), verbo([expressed]), complemento([in, 'HBV-related', 'HCC', 'tissues,', and, further, analysis, showed, that, this, lncRNA, was, induced, by, 'HBV', in, vitro])]). relacion([sujeto(['Functionally,', 'Unigene56159', significantly]), verbo([promoted]), complemento([cell, 'migration/invasion', and, 'epithelial-mesenchymal', transition, '(', 'EMT)', in, 'HCC'])]). relacion([sujeto(['Mechanistically,', 'Unigene56159', could, directly]), verbo([bind]), complemento([to, 'miR-140-5p', and, effectively, act, as, a, competing, endogenous, 'RNA', '(', 'ceRNA)', for, 'miR-140-5p', to, 'de-repress', the, expression, of, the, target, gene, 'Slug'])]). relacion([sujeto(['Collectively,', our, findings, indicate, that, the, 'Unigene56159/miR-140-5p/Slug', axis, contributes, to, 'HCC', cell, migration, and, 'invasion,', which, may]), verbo([provide]), complemento([novel, insights, into, the, function, of, 'lncRNA-driven', hepatocarcinogenesis])]). relacion([sujeto(['Incidental', and, secondary, findings]), verbo([have]), complemento([become, an, important, 'by-product', of, diagnostic, 'testing,', and, their, ramifications, affect, clinical, 'care,', 'research,', and, policy])]). relacion([sujeto(['Given', parallels, in, the]), verbo([reporting]), complemento([and, management, of, such, findings, on, diagnostic, 'imaging,', radiologists, may, draw, from, ongoing, discussions, in, medical, genetics, to, rethink, more, 'patient-centered', approaches, to, analogous, 'clinical,', 'ethical,', and, medicolegal, dilemmas])]). relacion([sujeto(['Low-risk', incidental, findings, in, particular, may, be, drivers, of, unnecessary, 'testing,', invasive, 'procedures,', and, 'overtreatment,', with]), verbo([associated]), complemento(['financial,', 'psychological,', and, clinical, consequences])]). relacion([sujeto(['As', radiologists]), verbo([act]), complemento([in, 'patients\'', best, interests, by, strengthening, standardized, guidelines, on, how, each, finding, merits, further, diagnostic, testing, or, 'treatment,', perhaps, the, greatest, challenge, for, producing, such, guidelines, is, for, 'low-risk', incidental, 'findings,', for, which, adverse, consequences, are, unlikely, but, associated, with, substantial, uncertainty, because, of, the, lack, of, strong, evidence, on, which, to, base, the, recommendations])]). relacion([sujeto(['More', uniform, recommendations, for, managing, 'low-risk', radiologic, incidental, findings, should, therefore, aim, to]), verbo([provide]), complemento([reasonable, options, that, apply, across, a, spectrum, of, patient, preferences])]). relacion([sujeto(['These', will]), verbo([require]), complemento([evaluation, through, research, and, will, ultimately, influence, the, quality, of, care])]). relacion([sujeto(['Because', of, the, broad, 'incidence,', morbidity, and, mortality]), verbo([associated]), complemento([with, 'prostate-derived', 'cancer,', the, development, of, more, effective, new, technologies, continues, to, be, an, important, goal, for, the, accurate, detection, and, treatment, of, localized, prostate, 'cancer,', lymphatic, involvement, and, metastases])]). relacion([sujeto(['Prostate-specific', membrane, antigen, '(', 'PSMA;', 'Glycoprotein', 'II)', is]), verbo([expressed]), complemento([in, high, levels, on, 'prostate-derived', cells, and, is, an, important, target, for, visualization, and, treatment, of, prostate, cancer])]). relacion([sujeto(['Radiolabeled', peptide]), verbo([targeting]), complemento([technologies, have, rapidly, evolved, over, the, last, decade, and, have, focused, on, the, successful, development, of, radiolabeled, small, molecules, that, act, as, inhibitors, to, the, binding, of, the, 'N-acetyl-l-aspartyl-l-glutamate', '(', 'NAAG)', substrate, to, the, 'PSMA', molecule])]). relacion([sujeto(['A', number, of, radiolabeled, 'PSMA', inhibitors]), verbo([have]), complemento([been, described, in, the, literature, and, labeled, with, 'SPECT,', 'PET', and, therapeutic, radionuclides])]). relacion([sujeto(['Clinical', studies, with, these, agents]), verbo([have]), complemento([demonstrated, the, improved, potential, of, 'PSMA-targeted', 'PET', imaging, agents, to, detect, metastatic, prostate, cancer, in, comparison, with, conventional, imaging, technologies])]). relacion([sujeto(['Although', many, of, these, agents]), verbo([have]), complemento([been, evaluated, in, 'humans,', by, far, the, most, extensive, clinical, literature, has, described, use, of, the, '(', 68, ')', 'Ga', and, '(', 177, ')', 'Lu', agents])]). relacion([sujeto(['This', review, describes, the, design, and, development, of, these, 'agents,', with, a, focus, on, the, broad, clinical, introduction, of, 'PSMA']), verbo([targeting]), complemento([motifs, labeled, with, '(', 68, ')', 'Ga', for, 'PET-CT', imaging, and, '(', 177, ')', 'Lu', for, therapy])]). relacion([sujeto(['In', 'particular,', because, of, availability, from, the, 'long-lived', '(', 68, ')', 'Ge', '(', 'T1/2=270days)/(68)Ga', '(', 'T1/2=68min)', generator, system, and]), verbo([increasing]), complemento([availability, of, 'PET-CT,', the, '(', 68, ')', 'Ga-labeled', 'PSMA', targeted, agent, is, receiving, widespread, interest, and, is, one, of, the, fastest, growing, radiopharmaceuticals, for, 'PET-CT', imaging])]). relacion([sujeto(['RECQ1,', the, most, abundant, one, of, the, human, 'RecQ', helicases, 'family,']), verbo([has]), complemento([been, identified, as, a, prometastasis, gene, in, breast, and, cervical, cancers])]). relacion([sujeto(['We']), verbo([found]), complemento([that, 'RECQ1', expression, was, significantly, higher, in, three, 'NSCLC', cell, lines, than, that, in, a, normal, human, bronchial, epithelial, cell, line])]). relacion([sujeto(['Knocking', down, 'RECQ1', significantly]), verbo([suppressed]), complemento(['A549', cell, 'proliferation,', migration, and, invasion])]). relacion([sujeto(['Taken', 'together,', our, findings]), verbo([suggest]), complemento([that, 'RECQ1', may, act, as, an, important, mediator, in, promoting, lung, cancer, progression, via, modulation, of, the, 'EMT'])]). relacion([sujeto(['RECQ1', might, represent, a, potential, therapeutic]), verbo([target]), complemento([in, 'NSCLC'])]). relacion([sujeto(['To', compare, the, maintenance, phase, behavior, of, eyes, with, a, shorter, induction, phase, '(', '≤3', 'injections)', with, those]), verbo([requiring]), complemento([a, longer, induction, phase, '(', &, 'gt;3', 'injections)'])]). relacion([sujeto(['For', analyses, by, 'visit:', choroidal, neovascular, membrane, activity, graded, by, the, treating, 'physician;', time, since, previous, 'injection;', and, visual, acuity]), verbo([loss]), complemento([since, previous, injection, '(', &, 'gt;0', letters, and, '≥15', 'letters)'])]). relacion([sujeto(['Median', treatment, interval]), verbo([increased]), complemento([from, 35, days, at, study, entry, to, 63, days, at, 12, months, and, was, 60, days, at, 36, months])]). relacion([sujeto(['Treatment', intervals, beyond, 12, weeks, seemed, to, be]), verbo([associated]), complemento([with, increased, risk, of, disease, 'reactivation,', with, risk, of, reactivation, reaching, 37.4, '%', at, treatment, intervals, of, '≥20', weeks])]). relacion([sujeto(['Visual', acuity, was, well]), verbo([maintained]), complemento([during, the, study, period])]). relacion([sujeto(['Longer', duration, of, induction, phase, was]), verbo([associated]), complemento([with, worse, visual, acuity, outcomes, and, earlier, disease, 'reactivation,', perhaps, because, of, undertreatment])]). relacion([sujeto(['Diaporine', is, a, novel, fungal, metabolic, product, and]), verbo([has]), complemento([an, unprecedented, symmetric, polyketide, with, a, novel, framework, from, diaporthe, sp])]). relacion([sujeto(['Firstly,', we, evaluate, the, sensitivities, of, diaporine, in, several, cancer, cells, and, the, results, show, that, diaporine]), verbo([has]), complemento(['proliferation-inhibitory', effect, against, cancer, cells, via, 'MTT', 'assay,', especially, on, breast, cancer, cells])]). relacion([sujeto(['In', 'addition,', we]), verbo([find]), complemento([that, diaporine, can, disrupt, the, morphology, and, viability, of, breast, cancer, cells, and, their, migration, and, invasion, capacities, are, also, impaired, tested, by, using, wound, healing, method, and, transwell])]). relacion([sujeto(['Further', investigation, show, that, diaporine, can, efficiently]), verbo([induce]), complemento([an, intensive, breast, cancer, cell, cycle, arrest, especially, in, 'G2', phase, and, finally, leads, to, cancer, cell, apoptosis, by, flow, cytometer, analysis])]). relacion([sujeto(['For', the, mechanism, by, which]), verbo([mediated]), complemento([the, breast, cancer, cell, 'death,', we, find, that, diaporine, can, induce, an, increase, of, 'ROS', level, in, breast, cancer, cells])]). relacion([sujeto(['Collectively,', our, results]), verbo([suggest]), complemento([that, diaporine, can, act, as, an, 'anti-cancer', agent, and, this, function, is, dependent, on, promoting, high, level, 'ROS', release, of, cancer, cells])]). relacion([sujeto(['Liver', resection]), verbo([has]), complemento([been, associated, with, high, morbidity, and, 'mortality,', and, the, most, serious, complication, is, liver, failure])]). relacion([sujeto(['The', 50, -, 50, criteria, and, bilirubin, 'peak>7mg/dl']), verbo([have]), complemento([been, used, as, mortality, predictors])]). relacion([sujeto(['The', aim, of, this, study, was, to, determine, the, risk, factors]), verbo([associated]), complemento([with, morbidity, and, mortality, for, liver, resection, in, our, population])]). relacion([sujeto(['Sociodemographic', 'variables,', 'pathology,', and, the, surgical]), verbo([act]), complemento([were, 'analyzed,', together, with, morbidity, and, mortality, and, their, associated, factors])]). relacion([sujeto(['The', 'Pringle', maneuver, was, used, in, 64.7, '%', of, the, cases, and, the, mean, blood]), verbo([loss]), complemento([was, 1, ',', 90, '±121'])]). relacion([sujeto(['Morbidity', of, 25.5, '%', was]), verbo([associated]), complemento([with, viral, hepatitis, 'infection,', greater, blood, 'loss,', transfusion, 'requirement,', the, 'Pringle', 'maneuver,', lower, hemoglobin, and, 'PTT', 'values,', and, higher, 'MELD,', 'INR,', 'bilirubin,', and, glucose, values])]). relacion([sujeto(['A', total, 3.9, '%', mortality, was]), verbo([associated]), complemento([with, 'hyperbilirubinemia,', 'hyperglycemia,', and, greater, blood, loss, and, transfusions])]). relacion([sujeto(['The', main, risk, factors]), verbo([associated]), complemento([with, the, morbidity, and, mortality, of, liver, resection, in, our, population, were, those, related, to, the, preoperative, biochemical, parameters, of, the, patient, and, the, factors, that, occurred, during, the, surgical, act])]). relacion([sujeto(['We', investigated, the, features, of, euthymic, bipolar, patients]), verbo([associated]), complemento([with, poor, sleep, 'quality,', with, a, focus, on, the, effect, of, childhood, trauma])]). relacion([sujeto([493, euthymic, patients, with, 'DSM-IV-defined', bipolar, disorders, were]), verbo([recruited]), complemento([in, 'FondaMental', 'Advanced', 'Centers', of, 'Expertize', for, 'Bipolar', 'Disorders', '(', 'FACE-BD)', between, 2009, and, 2014])]). relacion([sujeto(['Emotional', abuse, was]), verbo([associated]), complemento([with, poor, sleep, quality, after, adjustment, for, 'BMI,', 'age,', professional, 'activity,', and, bipolar, disorders, '(', 'BD)', type, '(', 'OR=1'])]). relacion([sujeto(['A', history, of, emotional, abuse, might, underlie, sleep, problems, in, many, bipolar, patients, but, anxiety, seems, to]), verbo([act]), complemento([as, a, confounding, factor, in, this, relationship])]). relacion([sujeto(['The', dysregulation, of, miRNA, expression, is]), verbo([associated]), complemento([with, oncogenic, transformation, and, miRNA, often, act, as, tumor, suppressors])]). relacion([sujeto(['Overexpression', of, 'miR-139-3p', significantly]), verbo([suppressed]), complemento(['HeLa', cell, 'proliferation,', migration, and, invasion, and, induced, cell, apoptosis])]). relacion([sujeto(['Bioinformatics', analysis, and, luciferase, reporter, gene, assay, confirmed, that, 'NOB1', was]), verbo([targeted]), complemento([by, 'miR-139-3p', at, the, 3, '\'', -, untranslated, region, '(', 3, '\'', 'UTR)', of, its, mRNA, sequence])]). relacion([sujeto(['Our', results]), verbo([suggest]), complemento([that, 'miR-139-3p', may, act, as, a, tumor, suppressor, that, can, inhibit, 'CC', cell, 'proliferation,', migration, and, invasion, and, induce, cell, apoptosis, through, 'down-regulation', of, 'NOB1', expression])]). relacion([sujeto(['Taken', 'together,', this, study]), verbo([provides]), complemento([a, novel, potential, therapeutic, strategy, for, the, treatment, of, 'CC'])]). relacion([sujeto(['MicroRNA-622']), verbo([has]), complemento([been, proven, 'down-regulated', in, many, human, malignancies, and, correlated, with, tumor, progression])]). relacion([sujeto(['miR-622', was]), verbo([found]), complemento([to, be, 'down-regulated', in, 'ESCC', tissues, and, cell, lines])]). relacion([sujeto(['Up-regulation', of, 'miR-622', could, significantly, reduce, 'ESCC', cell, 'proliferation,']), verbo([enhance]), complemento([cell, 'apoptosis,', and, impair, cell, invasion, and, migration, in, 'vitro,', while, 'down-regulation', of, 'miR-622', showed, opposite, effects])]). relacion([sujeto(['Further,', 'E2F1', was, confirmed, as, a, direct]), verbo([target]), complemento([of, 'miR-622', by, using, 'Luciferase', 'Reporter', 'Assay'])]). relacion([sujeto(['These', findings, indicate, that, 'miR-622', may]), verbo([act]), complemento([as, a, tumor, suppressor, in, 'ESCC', and, would, serve, as, a, potential, therapy, target, for, this, disease])]). relacion([sujeto(['Abiotic', and, biotic, stressors, also]), verbo([induce]), complemento([the, production, and, temporary, accumulation, of, 'ROS', in, 'plants,', including, hydrogen, peroxide, '(', 'H2O2),', whereby, they, can, act, as, secondary, 'messengers/chemical', mediators, in, plant, defense, signaling, and, lead, to, programmed, cell, death])]). relacion([sujeto(['H2O2']), verbo([acts]), complemento([as, a, hub, for, critical, information, flow, in, plants])]). relacion([sujeto(['In', this, study, we, also, quantified, constitutive, 'and/or']), verbo([induced]), complemento([levels, of, 'H2O2', in, three, model, 'plants,', 'Pinus', nigra, '(', 'Austrian', 'pine),', 'Oryza', sativa, '(', 'rice),', and, 'Arabidopsis', thaliana])]). relacion([sujeto(['Commonly', used, additives, for, 'H2O2', extraction, such, as]), verbo([activated]), complemento(['charcoal,', ammonium, 'sulfate,', perchloric, 'acid,', 'polyvinylpolypyrrolidone,', and, trichloroacetic, acid, either, degraded, 'H2O2', directly, or, interfered, with, the, 'Amplex', 'Red', assay])]). relacion([sujeto(['Finally,', 'We', measured, stability, of, 'Amplex', 'Red', working, solution, over, one, month, of, storage, at, -, 80, °, 'C', and]), verbo([found]), complemento([it, to, be, significantly, stable, over, time])]). relacion([sujeto(['This', gene, encodes, 'kindlin-1,', a, focal, adhesion, protein]), verbo([involved]), complemento([in, activation, of, the, integrin, family, of, extracellular, matrix, receptors])]). relacion([sujeto(['Electric', fields, also]), verbo([act]), complemento([as, intrinsic, regulators, of, adhesion, and, migration, in, the, 'skin,', but, the, molecular, mechanisms, by, which, this, occurs, are, poorly, understood])]). relacion([sujeto(['Here', we, show, that, keratinocytes, derived, from, 'KS', patients, are, unable, to, undergo, 'electrotaxis,', and, this, defect, is, restored, by, overexpression, of, 'wild-type', 'kindlin-1', but, not, a, 'W612A', mutation, that]), verbo([prevents]), complemento(['kindlin-integrin', binding])]). relacion([sujeto(['Moreover,', deletion, of, the, pleckstrin, homology, domain, of, 'kindlin-1', also, failed, to, rescue, electrotaxis, in, 'KS', 'cells,', indicating, that, both, integrin, and, lipid]), verbo([binding]), complemento([are, required, for, this, function])]). relacion([sujeto(['Kindlin-1', was, also]), verbo([required]), complemento([for, the, maintenance, of, lamellipodial, protrusions, during, electrotaxis, via, electric, 'field-activated', β1, integrin])]). relacion([sujeto(['Indeed,', inhibition, of, β1, integrins, also]), verbo([leads]), complemento([to, loss, of, electrotaxis, in, keratinocytes])]). relacion([sujeto(['Our', data]), verbo([suggest]), complemento([that, loss, of, 'kindlin-1', function, may, therefore, result, in, epithelial, insensitivity, to, electric, fields, and, contribute, to, 'KS', disease, pathology])]). relacion([sujeto(['Endogenously', produced, 'ROS']), verbo([act]), complemento([as, cellular, messengers, and, redox, regulators, involved, in, several, plant, biological, 'processes,', but, excessive, accumulation, of, 'ROS', cause, oxidative, stress, and, cell, damage])]). relacion([sujeto(['Understanding', 'ROS', signalling, and, stress, responses]), verbo([requires]), complemento([precise, imaging, and, quantification, of, 'local,', subcellular, and, global, 'ROS', dynamics, with, high, 'selectivity,', 'sensitivity,', and, spatiotemporal, resolution])]). relacion([sujeto(['Several', fluorescent, vital, dyes]), verbo([have]), complemento([been, tested, so, 'far,', which, helped, to, provide, relevant, spatially, resolved, information, of, oxidative, stress, dynamics, in, plants, subjected, to, harmful, environmental, conditions])]). relacion([sujeto(['The', development, of, improved, 'small-molecule', fluorescent, dyes, and, 'protein-based', 'ROS', sensors]), verbo([targeted]), complemento([to, subcellular, compartments, will, enable, in, vivo, monitoring, of, 'ROS', and, redox, changes, in, photosynthetic, organisms])]). relacion([sujeto(['The', key, role, of, 'RUNX3', in, physiological, 'T-cell', differentiation]), verbo([has]), complemento([been, extensively, documented])]). relacion([sujeto(['Re-expression', of, 'RUNX3/p46', reduces, cell, viability, and]), verbo([promotes]), complemento([apoptosis, in, a, 'RUNX3/p46(low)', cell, line, of, cutaneous, 'T-cell', lymphoma])]). relacion([sujeto(['Based', on, 'this,', we, present, evidence, that, 'RUNX3', can]), verbo([act]), complemento([as, a, tumor, suppressor, in, a, human, 'T-cell', malignancy, and, suggest, that, this, effect, is, predominantly, mediated, through, transcripts, from, its, distal, 'promoter,', in, particular, 'RUNX3/p46'])]). relacion([sujeto(['Previous', studies]), verbo([have]), complemento([examined, participation, in, specific, 'leisure-time', physical, activities, '(', 'PA)', among, 'US', adults])]). relacion([sujeto(['The', proportion, was, lower, for, 'walking,', but, higher, for, 'sports,', among, active, adults, than, those, insufficiently, active, and]), verbo([increased]), complemento([with, age, for, walking])]). relacion([sujeto(['Although', individual, studies]), verbo([have]), complemento([reported, on, the, number, of, 'steps/day', taken, by, individuals, with, 'COPD,', this, evidence, has, not, been, systematically, reviewed, or, synthesized])]). relacion([sujeto(['MEDLINE', and, 'PsycINFO', were, searched, for, studies]), verbo([reporting]), complemento(['objectively-measured', 'steps/day', and, percent, predicted, forced, expiratory, volume, in, one, second, '(', 'FEV1%)', in, patients, with, 'COPD'])]). relacion([sujeto(['In', a, multivariate, model, including, the, above, risk, 'factors,', only, 'FEV1%', was]), verbo([associated]), complemento([with, 'steps/day', after, adjustment, for, other, covariates])]). relacion([sujeto(['These', results, indicate, that, patients, with, 'COPD', achieve, extremely, low, levels, of, physical, activity, as, assessed, by, 'steps/day,', and, that, severity, of, airflow, obstruction, is]), verbo([associated]), complemento([with, activity, level])]). relacion([sujeto(['Adults', who, reached, '≥7,500', 'steps/day', presented, a, lower, likelihood, of, being, obese, '(', 'OR=', 0.38, '[', 0.17, -, 0.85, ']', ')', and]), verbo([reported]), complemento([worse, sleep, quality, '(', 'OR=', 0.58, '[', 0.34, -, 0.99, ']', ')', ',', while, reaching, &, 'lt;5,000', 'steps/day', was, associated, with, a, higher, likelihood, of, worse, sleep, quality, '(', 'OR=', 2.11, '[', 1.17, -, 3.82, ']', ')'])]). relacion([sujeto(['These', findings]), verbo([suggest]), complemento([that, unsupervised, physical, activity, is, sufficient, in, improving, 'CRF', in, both, genders])]). relacion([sujeto(['Furthermore,', larger, muscle, mass, and, better, balance, are]), verbo([associated]), complemento([with, higher, 'CRF', that, has, to, be, taken, into, account, when, assessing, 'CRF', using, maximal, cycle, ergometer, exercise, test, among, children])]). relacion([sujeto(['Screen-time', of, adolescents]), verbo([has]), complemento([been, associated, with, obesity, and, other, adverse, health, 'outcomes;', 'however,', little, is, known, about, 'screen-based', behaviours, in, 'Asian', adolescents])]). relacion([sujeto(['Median']), verbo([reported]), complemento([recreational, 'screen-time', was, 4.0, 'h/day', with, longer, times, among, boys, '(', 4.3, 'h/day)', than, girls, '(', 3.6, 'h/day)'])]). relacion([sujeto(['Multivariable', analyses, showed, that, high, 'screen-time', was, more, common, among, boys, than, 'girls,', and, positively]), verbo([associated]), complemento([with, commuting, to, school, by, 'car,', consumption, of, fast, food, '≥3', 'times/week,', having, sleep, 'disturbance,', and, high, family, income])]). relacion([sujeto(['There', was, a, significant]), verbo([increase]), complemento([in, body, satisfaction, following, the, yoga, class])]). relacion([sujeto(['Following', both, 'classes,', there, was, a, significant]), verbo([decrease]), complemento([in, social, physique, anxiety, but, the, magnitude, of, the, changes, was, larger, following, the, yoga, class, than, the, resistance, class])]). relacion([sujeto(['Both', types, of, exercise, class, were]), verbo([associated]), complemento([with, improvements, in, body, 'image,', with, greater, improvements, following, the, yoga, class])]). relacion([sujeto(['This', study]), verbo([provided]), complemento([evidence, of, the, positive, effects, of, yoga, for, reducing, state, social, physique, anxiety, and, increasing, state, body, 'satisfaction,', adding, to, correlational, evidence, suggesting, yoga, session, be, particularly, beneficial, for, improving, body, 'image-related', outcomes, in, women])]). relacion([sujeto(['Complete', streets]), verbo([require]), complemento([evaluation, to, determine, if, they, encourage, active, transportation])]). relacion([sujeto(['Data', were, collected, before, and, after, a, street, intervention]), verbo([provided]), complemento([new, light, 'rail,', bike, 'lanes,', and, better, sidewalks, in, 'Salt', 'Lake', 'City,', 'Utah'])]). relacion([sujeto(['Living', near, the, complete, street, intervention, supported, more, pedestrian, use, and, possibly, 'bicycling,']), verbo([suggesting]), complemento([complete, streets, are, also, public, health, interventions])]). relacion([sujeto(['It', remains, unclear, whether, 'self-regulated', exercise, is, sufficient, to]), verbo([maintain]), complemento([the, benefits, acquired, during, formal, cardiac, rehabilitation, '(', 'CR)'])]). relacion([sujeto(['Fifty', patients, with, cardiovascular, disease, were, discharged, after, 6, months, of, 'CR', and, encouraged, to]), verbo([maintain]), complemento([aerobic, exercise, without, supervision])]). relacion([sujeto(['At', the, end, of, the, 'follow-up,', statistical, differences, across, groups, were, not]), verbo([found]), complemento([for, body, mass, or, body, mass, 'index,', but, increases, in, 'VO2peak', '(', +, 3.6, vs])]). relacion([sujeto(['Self-regulated', exercising, following, 'CR', discharge, seems, to, be, effective, to]), verbo([maintain]), complemento([gains, in, exercise, capacity, acquired, during, supervised, 'center-based', programs])]). relacion([sujeto(['The', aim, of, this, study, was, to, evaluate, the, association, between, physical, activity, from, 11, to, 15, years, of, age, and, pulmonary, function, '(', 'PF)']), verbo([gain]), complemento([from, 15, to, 18, years, of, age, among, adolescents, in, a, birth, cohort, in, 'Brazil'])]). relacion([sujeto(['Longitudinal', analysis, of, the, individuals]), verbo([participating]), complemento([in, the, 1993, 'Pelotas', 'Birth', 'Cohort', 'Study'])]). relacion([sujeto(['Outcome', variables, assessed, were]), verbo([gains]), complemento([in, forced, expiratory, volume, in, one, second, '(', 'FEV1),', forced, vital, capacity, '(', 'FVC)', and, peak, expiratory, flow, '(', 'PEF)'])]). relacion([sujeto(['Boys', who, were, active, '(', 'leisure-time', and, total, physical, 'activity)', at, ages, 11, and, 15, had, higher]), verbo([gains]), complemento([in, 'FEV1,', 'FVC,', and, 'PEF', than, those, who, were, inactive])]). relacion([sujeto(['Vigorous-intensity', physical, activity, in, boys, was, also]), verbo([associated]), complemento([with, 'FEV1', and, 'FVC', gains])]). relacion([sujeto(['No', significant, associations, were]), verbo([found]), complemento([amongst, girls])]). relacion([sujeto(['Physical', activity, in, early, adolescence, is]), verbo([associated]), complemento([with, gains, in, 'PF', by, the, end, of, adolescence, in, boys])]). relacion([sujeto(['Effective', interventions, are, needed, to]), verbo([increase]), complemento([physical, activity, in, the, general, population])]). relacion([sujeto(['To']), verbo([target]), complemento([interventions, we, need, knowledge, of, insufficiently, active, groups, in, society])]). relacion([sujeto(['A', lower, prevalence, of, inactivity, was]), verbo([associated]), complemento([with, middle, 'age,', higher, 'education,', having, previous, experience, of, sports, 'participation,', following, a, 'GI/Mediterranean', diet, and, having, a, light, physical, workload])]). relacion([sujeto(['A', high, prevalence, of, inactivity, was]), verbo([associated]), complemento([with, high, 'age,', high, body, mass, 'index,', 'smoking,', being, a, never, drinker, of, 'alcohol,', having, 'children,', a, weak, social, network, or, lower, levels, of, emotional, 'support,', and, a, low, vegetable, intake])]). relacion([sujeto(['Several', factors, were]), verbo([associated]), complemento([with, leisure, time, physical, inactivity])]). relacion([sujeto(['Directing', interventions, to]), verbo([target]), complemento([groups, defined, by, specific, factors, associated, with, physical, inactivity, could, be, an, efficient, way, to, increase, activity, and, improve, health, in, the, general, population])]). relacion([sujeto(['Erbin,', 'Lano,', 'Scribble,', and, 'Densin-180', belong, to, 'LAP', '(', 'leucine-rich', repeats, and, 'PDZ', 'domain)', adaptor, proteins]), verbo([involved]), complemento([in, cell, signaling, pathways])]). relacion([sujeto(['Previously,', we, identified, 'Erbin,', 'Lano,', and, 'Scribble,', but, not, 'Densin-180,', in, muscle, 'cells,', where, they, are]), verbo([involved]), complemento([in, regulating, the, aggregation, of, nicotinic, acetylcholine, receptors, 'in vitro'])]). relacion([sujeto(['We', used, two, 'Erbin', mutant, mouse, strains, that, either, completely, lack, 'Erbin', protein, '(', 'Erbin(null/null)', ')', or]), verbo([express]), complemento([a, truncated, 'Erbin', mutant, where, the, 'carboxy-terminal', 'PDZ', domain, is, replaced, by, 'β-galactosidase', '(', 'Erbin(ΔC/ΔC)', ')', thereby, abolishing, its, interaction, with, 'ErbB', receptor, tyrosine, kinases])]). relacion([sujeto(['Erbin-null', skeletal, muscles, did, not]), verbo([reveal]), complemento([any, conspicuous, impairment, of, the, muscle, fiber])]). relacion([sujeto(['We', speculate, that, 'Erbin,', 'Lano,', and, 'Scribble']), verbo([act]), complemento([at, the, 'post-synaptic', membrane, of, 'NMJs', in, a, concerted, fashion, to, regulate, nicotinic, acetylcholine, receptors, cluster, morphology, and, neural, transmission])]). relacion([sujeto(['At', low, 'levels,', reactive, oxygen, species, '(', 'ROS)', can]), verbo([act]), complemento([as, signaling, molecules, within, cells])]). relacion([sujeto(['When', 'ROS', production, greatly, exceeds, the, capacity, of, endogenous, antioxidant, 'systems,', or, antioxidant, levels, are, 'reduced,', 'ROS', levels]), verbo([increase]), complemento([further])]). relacion([sujeto(['The', latter, is]), verbo([associated]), complemento([with, induction, of, oxidative, stress, and, associated, signal, transduction, and, characterized, by, 'ROS-induced', changes, in, cellular, redox, homeostasis, 'and/or', damaging, effects, on, biomolecules, '(', e])]). relacion([sujeto(['Given', the, complex, mechanisms]), verbo([involved]), complemento([in, 'ROS', production, and, 'removal,', in, combination, with, the, lack, of, reporter, molecules, that, are, truly, specific, for, a, particular, type, of, 'ROS,', quantification, of, '(', 'sub)cellular', 'ROS', levels, is, a, challenging, task])]). relacion([sujeto(['Bacterial', blight, '(', 'BB)', and, bacterial, leaf, streak, '(', 'BLS)', are, important, diseases, in, 'Oryza', sativa]), verbo([caused]), complemento([by, 'Xanthomonas', oryzae, pv])]). relacion([sujeto(['In', both, 'bacteria,', transcription, 'activator-like', '(', 'TAL)', effectors, are, major, virulence, determinants, that]), verbo([act]), complemento([by, transactivating, host, genes, downstream, of, 'effector-binding', elements, '(', 'EBEs)', bound, in, a, 'sequence-specific', manner])]). relacion([sujeto(['Resistance', to, 'Xoo', is, mostly, related, to, the, action, of, 'TAL', 'effectors,', either, by, polymorphisms, that]), verbo([prevent]), complemento([the, induction, of, susceptibility, '(', 'S)', genes, or, by, executor, '(', 'R)', genes, with, 'EBEs', embedded, in, their, 'promoter,', and, that, induce, cell, death, and, resistance])]). relacion([sujeto(['Here,', we, investigated, whether, the, recognition, of, effectors, by, nucleotide]), verbo([binding]), complemento([and, 'leucine-rich', repeat, domain, immune, receptors, '(', 'NLRs),', the, most, widespread, resistance, mechanism, in, 'plants,', is, also, able, to, stop, 'BB', and, 'BLS'])]). relacion([sujeto(['This']), verbo([induced]), complemento(['AVR1-CO39', expression, and, triggered, 'BB', and, 'BLS', resistance, when, the, corresponding, 'Pi-CO39', resistance, locus, was, present])]). relacion([sujeto(['This', forms, the, foundation, for, future, 'BB', and, 'BLS', disease, control, 'strategies,', whereupon, endogenous, 'TAL', effectors, will]), verbo([target]), complemento([synthetic, promoter, regions, of, 'Avr', or, 'NLR', executor, genes])]). relacion([sujeto(['We', assessed, physical, activity, patterns, and]), verbo([associated]), complemento([factors, among, adults])]). relacion([sujeto(['Logistic', regression, was, conducted, to, identify, factors]), verbo([associated]), complemento([with, physical, inactivity, and, sedentary, behaviour])]). relacion([sujeto(['Factors']), verbo([associated]), complemento([with, sedentary, behaviour, were, being, 'female,', '≥', 65, 'years,', 'peri-urban', 'residence,', being, a, domestic, 'worker,', formal, employment, and, lower, primary, education])]). relacion([sujeto(['Factors']), verbo([associated]), complemento([with, physical, inactivity, were, being, 'female,', 55, -, 64, 'years,', '≥', 65, 'years,', 'peri-urban', 'residence,', overweight, and, obesity])]). relacion([sujeto(['The', electrodes, can]), verbo([act]), complemento([as, either, electron, sinks, or, sources, that, allow, unbalanced, fermentation])]). relacion([sujeto(['We', also, explore, the, 'up-to-date', strategies, to, put, 'EF', into, practice, and, propose, hypothetical, mechanisms, that, could, explain, the, first, 'EF', results]), verbo([reported]), complemento([in, the, literature])]). relacion([sujeto(['Emergency', physicians, frequently]), verbo([interact]), complemento([with, law, enforcement, officers, and, patients, in, their, custody])]). relacion([sujeto(['As', 'always,', the, emergency, 'physician\'s', primary, professional, responsibility, is, to]), verbo([promote]), complemento([patient, 'welfare,', and, his, or, her, first, duty, is, to, the, patient])]). relacion([sujeto(['Emergency', physicians, should, treat, 'criminals,', 'suspects,', and, prisoners, with, the, same, respect, and, attention, they, afford, other, patients, while]), verbo([ensuring]), complemento([the, safety, of, 'staff,', 'visitors,', and, other, patients])]). relacion([sujeto(['Often', this, relates, to, the, emergency, 'physician\'s', socially, imposed, 'duties,', governed, by, state, 'laws,', to]), verbo([report]), complemento([infectious, 'diseases,', suspicion, of, abuse, or, 'neglect,', and, threats, of, harm])]). relacion([sujeto(['It', is, the, emergency, 'physician\'s', duty, to]), verbo([maintain]), complemento([patient, confidentiality, while, complying, with, 'Health', 'Insurance', 'Portability', and, 'Accountability', 'Act', regulations, and, state, law])]). relacion([sujeto(['Village', midwives]), verbo([have]), complemento([been, popular, in, 'Brunei', since, the, 1900, 's,', with, their, major, role, being, to, assist, women, with, childbirth])]). relacion([sujeto(['However,', since, the, 1960, 's,', their, roles, and, practices]), verbo([have]), complemento([changed, to, focus, on, 'pre-conception,', 'antenatal,', postnatal, and, 'women\'s', general, healthcare])]). relacion([sujeto(['In,', many, high, and, 'middle-income', 'countries,', childbearing, women]), verbo([have]), complemento([a, variety, of, birthplaces, available, to, them, including, 'home,', birth, centres, and, traditional, labour, wards])]). relacion([sujeto(['Data', were, gathered, through, focus, groups, conducted, with, midwives, in, 'Australia', and, in, the, 'United', 'Kingdom', who, worked, in, 'publicly-funded', maternity, services, and, who]), verbo([provided]), complemento([labour, and, birth, care, in, at, least, two, different, settings])]). relacion([sujeto(['Given', the, excellent, outcomes, of, midwifery]), verbo([led]), complemento(['care,', we, should, focus, on, how, we, can, facilitate, the, work, of, midwives, in, all, settings])]). relacion([sujeto(['This', study]), verbo([suggests]), complemento([that, the, culture, of, the, birthplace, rather, than, the, physicality, is, the, highest, priority])]). relacion([sujeto(['Although', visfatin, is, an, adipocytokine, highly]), verbo([expressed]), complemento([in, visceral, fat, that, has, been, demonstrated, to, play, a, critical, role, in, the, progression, of, human, 'malignancies,', little, is, known, about, the, role, of, visfatin, in, 'HCC', associated, with, chronic, hepatitis, 'C', virus, '(', 'HCV)', and, hepatitis, 'B', virus, '(', 'HBV)', infection])]). relacion([sujeto([46, ')', were, independently]), verbo([associated]), complemento([with, 'HCC'])]). relacion([sujeto(['Multiple', stepwise, regression, analysis, showed, that, plasma, visfatin, level, was, positively]), verbo([associated]), complemento([with, 'age,', aspartate, aminotransferase, to, platelet, ratio, index, '(', 'APRI),', and, 'AFP'])]). relacion([sujeto(['Trend', analyses, confirmed, that, plasma, visfatin, concentration, was]), verbo([associated]), complemento([with, 'AFP>8ng/mL,', 'cirrhosis,', 'HCC,', tumor, 'size>5cm,', and, 'Barcelona', 'Clinic', 'Liver', 'Cancer-C', stage])]). relacion([sujeto(['These', results]), verbo([suggested]), complemento([that, the, plasma, visfatin, level, is, associated, with, the, presence, of, 'HCC,', and, that, a, higher, plasma, visfatin, level, may, be, important, in, the, pathogenesis, of, 'HCC'])]). relacion([sujeto(['Visfatin', may]), verbo([act]), complemento([as, both, a, protective, and, 'pro-inflammatory', factor])]). relacion([sujeto(['Hendra', virus, '(', 'HeV)']), verbo([causes]), complemento([potentially, fatal, respiratory, 'and/or', neurological, disease, in, both, horses, and, humans])]). relacion([sujeto(['Although', 'Australian', 'flying-foxes', of, the, genus, 'Pteropus']), verbo([have]), complemento([been, identified, as, reservoir, 'hosts,', the, precise, mechanism, of, 'HeV', transmission, has, yet, to, be, elucidated])]). relacion([sujeto(['To', 'date,', there]), verbo([has]), complemento([been, limited, investigation, into, the, role, of, haematophagous, insects, as, vectors, of, 'HeV'])]). relacion([sujeto(['We']), verbo([found]), complemento([no, evidence, of, 'HeV', in, any, bat, flies, 'tested,', including, 10, bat, flies, collected, from, 'P'])]). relacion([sujeto(['Our', negative, findings, are, consistent, with, previous, findings, and]), verbo([provide]), complemento([additional, evidence, that, bat, flies, do, not, play, a, primary, role, in, 'HeV', transmission])]). relacion([sujeto(['Research', over, the, past, several, decades]), verbo([has]), complemento([addressed, a, major, issue, that, can, occur, when, using, these, 'biocatalysts,', i])]). relacion([sujeto([',', slow, heterogeneous, electron, 'transfer,', by, incorporation, of, a, redox, active, species, to]), verbo([act]), complemento([as, an, electron, shuttle])]). relacion([sujeto(['There', are, several, advantages, to, immobilizing, both, the, enzyme, and, mediator, at, the, enzyme, 'surface,', including]), verbo([increased]), complemento([electron, transfer, 'rates,', decreased, enzyme, 'leaching,', and, minimized, diffusion, limitations])]). relacion([sujeto(['Redox', polymers, consisting, of, a, redox, active, center, attached, to, a, polymer, backbone, are, a, particularly, attractive, option, because, they]), verbo([have]), complemento([high, 'self-exchange', rates, for, electron, transfer, and, tunable, redox, potential])]). relacion([sujeto(['The', 'School', of, 'Health', and, 'Related', 'Research', 'Technology', 'Appraisal', 'Group', at, the, 'University', of, 'Sheffield', was, commissioned, to]), verbo([act]), complemento([as, the, independent, 'Evidence', 'Review', 'Group', '(', 'ERG)'])]). relacion([sujeto(['Neither', abiraterone, nor, enzalutamide]), verbo([has]), complemento([been, directly, compared, in, a, trial, with, cabazitaxel])]). relacion([sujeto(['Results', from, 'TROPIC', showed, that, cabazitaxel, was]), verbo([associated]), complemento([with, a, statistically, significant, improvement, in, both, overall, survival, and, 'progression-free', survival, compared, with, mitoxantrone])]). relacion([sujeto(['Hence,', its, exclusion]), verbo([leads]), complemento([to, uncertainty, in, the, 'cost-effectiveness', results])]). relacion([sujeto(['In', 'addition,', the, company, assumed, that, there, would, be, no, drug, wastage, when, cabazitaxel, was, 'used,', with, 'cost-effectiveness', results, being, sensitive, to, this, 'assumption:', modelling, drug, wastage]), verbo([increased]), complemento([the, 'ICER', comparing, cabazitaxel, with, mitoxantrone, to, over, '£55,000', per, 'QALY', gained])]). relacion([sujeto(['In', 'response,', the, company]), verbo([provided]), complemento([both, a, further, discount, to, the, confidential, 'PAS', for, cabazitaxel, and, confirmation, from, 'NHS', 'England', that, it, is, appropriate, to, supply, and, purchase, cabazitaxel, in, 'pre-prepared', 'intravenous-infusion', 'bags,', which, would, remove, the, cost, of, drug, wastage])]). relacion([sujeto(['As', a, 'result,', the, committee, recommended, use, of, cabazitaxel, as, a, treatment, option, in, people, with, an, 'Eastern', 'Cooperative', 'Oncology', 'Group', performance, status, of, 0, or, 1, whose, disease, had, progressed, during, or, after, treatment, with, at, least, 225, &, 'nbsp;mg/m(2)', of, 'docetaxel,', as, long, as, it, was]), verbo([provided]), complemento([at, the, discount, agreed, in, the, 'PAS', and, purchased, in, either, 'pre-prepared', 'intravenous-infusion', bags, or, in, vials, at, a, reduced, price, to, reflect, the, average, 'per-patient', drug, wastage])]). relacion([sujeto(['Based', on, 'in-depth', interviews, with, 16, heterosexual, 'men,', this, study, focuses, on, 'participants\'', 'meaning-making', surrounding, a, common, and, controversial, sexual]), verbo([act]), complemento([in, 'pornography:', ejaculation, on, a, 'woman\'s', face, '(', 'EOWF)'])]). relacion([sujeto(['The', majority, of, the, men, decoded, 'EOWF', through, the, preferred, '(', 'encoded)', meaning, as, an]), verbo([act]), complemento([of, male, dominance, and, sexual, aggression, and, that, they, wanted, to, engage, in, it, despite, their, general, belief, that, women, would, not, be, interested, in, it])]). relacion([sujeto(['The', major, reasons, for, patients, to, request, 'DWD', as]), verbo([reported]), complemento([by, participating, physicians, were, loss, of, autonomy, and, dignity, and, decrease, in, enjoyable, activities])]). relacion([sujeto(['Inadequate', pain, 'control,', financial, 'cost,', and]), verbo([loss]), complemento([of, bodily, control, were, less, commonly, indicated])]). relacion([sujeto(['Furthermore,', compared, to, the, 'all-cause', 'DWD', 'cohort,', patients, with, 'ALS', are, more, likely, to, be, 'non-Hispanic', 'white,', 'married,', 'educated,', enrolled, in, 'hospice,', and, to]), verbo([have]), complemento([died, at, home])]). relacion([sujeto(['Although', a, small, 'number,', 'ALS', represents, the, disease, with, the, highest, proportion, of, patients, seeking, to]), verbo([participate]), complemento([in, 'DWD'])]). relacion([sujeto(['Patients', with, 'ALS', who, choose, 'DWD', are, 'well-educated', and]), verbo([have]), complemento([access, to, palliative, or, 'life-prolonging', care])]). relacion([sujeto(['Research']), verbo([has]), complemento([shown, that, people, who, feel, powerful, are, more, likely, to, act, than, those, who, feel, 'powerless,', whereas, people, who, feel, ambivalent, are, less, likely, to, act, than, those, whose, reactions, are, univalent, '(', entirely, positive, or, entirely, 'negative)'])]). relacion([sujeto(['But', what, happens, when, powerful, people, also, are, 'ambivalent?', 'On', the, basis, of, the, 'self-validation', theory, of, 'judgment,', we, hypothesized, that, power, and, ambivalence, would]), verbo([interact]), complemento([to, predict, 'individuals\'', action])]). relacion([sujeto(['Because', power, can, validate, 'individuals\'', 'reactions,', we, reasoned, that, feeling, powerful, strengthens, whatever, reactions, people]), verbo([have]), complemento([during, a, decision])]). relacion([sujeto(['It', can, strengthen, univalent, reactions, and]), verbo([increase]), complemento([action, 'orientation,', as, shown, in, past, research])]). relacion([sujeto(['Two', experiments]), verbo([provide]), complemento([evidence, for, this, hypothesized, interactive, effect, of, power, and, ambivalence, on, 'individuals\'', action, tendencies, during, both, positive, decisions, '(', promoting, an, 'employee;', 'Experiment', 1, ')', and, negative, decisions, '(', firing, an, 'employee;', 'Experiment', 2, ')'])]). relacion([sujeto(['In', 'summary,', when, 'individuals\'', reactions, are, 'ambivalent,', power]), verbo([increases]), complemento([the, likelihood, of, inaction])]). relacion([sujeto(['Cilia', are, plasma, membrane, protrusions, that]), verbo([act]), complemento([as, cellular, propellers, or, antennae])]). relacion([sujeto(['To', perform, these, 'functions,', cilia, must]), verbo([maintain]), complemento([a, composition, distinct, from, those, of, the, contiguous, cytosol, and, plasma, membrane])]). relacion([sujeto(['Accordingly,', many, human, ciliopathies, are]), verbo([caused]), complemento([by, mutations, that, perturb, ciliary, gate, function])]). relacion([sujeto(['We', sought, to]), verbo([find]), complemento([the, most, 'safe,', 'effective,', and, rapid, method, for, performing, the, 'conceptually-simple', yet, 'technically-nuanced', act, of, replacing, lead, extension, cables])]). relacion([sujeto(['Care', was]), verbo([provided]), complemento([in, 'ZIP', 'code-matched', locations, and, at, 2, 'employers\'', worksites])]). relacion([sujeto(['A', network, of, 50, trained, pharmacists]), verbo([provided]), complemento([chronic, disease, management, to, patients, with, diabetes, using, a, common, process, of, care])]). relacion([sujeto(['Communications', were]), verbo([provided]), complemento([to, patients, and, physicians])]). relacion([sujeto(['Employers']), verbo([provided]), complemento([incentives, for, patients, who, opted, 'in,', including, waived, medication, copayments, and, free, diabetes, 'self-monitoring', supplies])]). relacion([sujeto(['The', service, was]), verbo([provided]), complemento([at, no, cost, to, the, patient])]). relacion([sujeto(['Quality', assurance, was, conducted, to]), verbo([ensure]), complemento([the, standard, of, care])]). relacion([sujeto(['Statistically', significant, improvements, were, shown, by, mean]), verbo([decreases]), complemento([in, 'A1c', '(', -, 0.41, '%', ',', &, 'nbsp;P', &, 'lt;0'])]). relacion([sujeto(['Pharmacist-provided', comprehensive, medication, therapy, management, services, should, be, included, as, a]), verbo([required]), complemento([element, of, insurance, offered, by, employers, and, health, insurance, exchanges])]). relacion([sujeto(['Peptide', 'ligand-receptor', kinase, interactions]), verbo([have]), complemento([emerged, as, a, key, component, of, plant, growth, and, development])]). relacion([sujeto(['Now,', highly, related, small, signaling, peptides]), verbo([have]), complemento([been, shown, to, act, antagonistically, on, the, same, receptor, 'kinase,', providing, new, insights, into, how, plants, optimize, developmental, processes, using, competitive, peptides])]). relacion([sujeto(['Ticks', harbour, various, 'microorganisms,', some, of, which]), verbo([act]), complemento([as, pathogens, of, humans, and, animals])]). relacion([sujeto(['Continuous', cell, lines, established, from, ticks, could, play, a, key, role, in, the, isolation, of, such, 'microorganisms;', 'however,', tick, cells, themselves]), verbo([have]), complemento([been, known, to, harbour, symbiotic, microorganisms])]). relacion([sujeto(['The', results]), verbo([suggested]), complemento([that, there, were, at, least, five, putative, viral, sequences, of, four, phylogenetically, distinct, lineages, in, 'ISE6', cells])]). relacion([sujeto(['The', predominant, viral, sequence]), verbo([found]), complemento([in, 'ISE6', 'cells,', designated, 'I'])]). relacion([sujeto(['scapularis-associated', 'virus-1,', which, was]), verbo([reported]), complemento([in, a, recent, metagenomic, study, of, 'I'])]). relacion([sujeto(['Further', studies, are]), verbo([required]), complemento([to, investigate, the, potential, roles, of, 'ISE6-associated', viruses, in, ticks])]). relacion([sujeto(['The', obtained, 'BMSA-Al(3+)', and, 'BMSA-Cu(2+)', complexes, could]), verbo([act]), complemento([as, cascade, sensors, for, detecting, 'F(-)', and, 'S(2-),', respectively])]). relacion([sujeto(['The']), verbo([recognizing]), complemento([behavior, of, 'BMSA', toward, 'Al(3+)and', 'Cu(2+)', has, been, investigated, in, detail, through, 'Job\'s', 'Plot,', 'FT-IR', 'NMR,', and, 'HRMS', analysis])]). relacion([sujeto(['Moreover,', this, chemosensor, was, verified, to, be, of, low, cytotoxicity, and, good, imaging, characteristics, for, the, detection, of, 'Al(3)(+)', and, 'Cu(2+),', and, further, for, the, recognition, of, 'F(-)', and, 'S(2-)', in, living, 'cells,']), verbo([suggesting]), complemento([that, 'BMSA', was, proved, to, be, a, useful, tool, for, tracking, 'Al3(+)/Cu(2+)and', 'F(-)/S(2-)', ions, in, vivo])]). relacion([sujeto(['Progress', to, date, through, multiple, sets, of, initiatives, and, partners, to, contain, or, eliminate, these, parasites]), verbo([has]), complemento([been, hampered, due, to, a, wide, range, of, 'organizational,', 'financial,', and, health, 'systems-level', challenges])]). relacion([sujeto(['These', actions, are, specifically, needed, to, elevate, the, situation, and, response, mechanisms, to, those, of, a, true, 'emergency;', to, address, 'systems-level', challenges, with, personnel, limitations, and, 'stock-outs', of, key, 'commodities;', and, to, restructure, the, response, mechanisms, to, be, 'well-aligned', with, the]), verbo([required]), complemento([outcomes])]). relacion([sujeto(['Whilst', 'multi-parametric', magnetic, resonance, imaging, '(', 'mp-MRI)']), verbo([has]), complemento([been, a, significant, advance, in, the, diagnosis, of, prostate, 'cancer,', scanning, all, patients, with, elevated, prostate, specific, antigen, '(', 'PSA)', levels, is, considered, too, costly, for, widespread, 'National', 'Health', 'Service', '(', 'NHS)', 'use,', as, the, predictive, value, of, 'PSA', levels, for, significant, disease, is, poor])]). relacion([sujeto(['Furthermore', approximately, 40, &, 'nbsp;%', of, 'mp-MRI', studies, are]), verbo([reported]), complemento([as, 'indeterminate,', which, can, lead, to, repeat, examinations, or, unnecessary, biopsy, with, associated, patient, 'anxiety,', 'discomfort,', risk, and, additional, costs])]). relacion([sujeto(['mp-MRI', will]), verbo([act]), complemento([as, the, reference, standard, for, the, biomarker, panel])]). relacion([sujeto([bolteae, contained, lactose, operons]), verbo([involving]), complemento(['PTS', system, and, complex, 'regulation,', which, contribute, to, phenotypic, differentiation, from, 'C'])]). relacion([sujeto(['The', 'Acetyl-CoA', 'pathway,', similar, to, that, of, 'Faecalibacterium', 'prausnitzii,', a, major, butyrate, producer, in, the, human, 'gut,', was, only]), verbo([found]), complemento([in, 'C'])]). relacion([sujeto(['The', two, species]), verbo([have]), complemento([also, developed, diverse, flagella, mobility, systems, contributing, to, gut, colonization])]). relacion([sujeto(['Their', genomes, harboured, many, 'CDSs']), verbo([involved]), complemento([in, resistance, to, 'beta-lactams,', 'glycopeptides,', 'macrolides,', 'chloramphenicol,', 'lincosamides,', 'rifampin,', 'linezolid,', 'bacitracin,', aminoglycosides, and, tetracyclines])]). relacion([sujeto([clostridioforme, 90, 'A8', contained, the, 'VanB-type', 'Tn1549', operon]), verbo([conferring]), complemento([vancomycin, resistance])]). relacion([sujeto(['Some', were, part, of, mobile, genetic, elements]), verbo([suggesting]), complemento([that, these, commensals, of, the, human, microbiota, act, as, reservoir, of, antimicrobial, resistances])]). relacion([sujeto(['Mechanical', loading, is, the, primary, functional, determinant, of, bone, mass, and, 'architecture,', and, osteocytes, play, a, key, role, in]), verbo([translating]), complemento([mechanical, signals, into, '(', 're)modelling', responses])]). relacion([sujeto(['Although', the, precise, mechanisms, remain, 'unclear,', 'Wnt', signalling, pathway, 'components,', and, the, 'anti-osteogenic', canonical, 'Wnt', inhibitor, 'Sost/sclerostin', in, 'particular,', play, an, important, role, in]), verbo([regulating]), complemento(['bone\'s', adaptive, response, to, loading])]). relacion([sujeto(['Increases', in, 'loading-engendered', strains, 'down-regulate', osteocyte, sclerostin, 'expression,', whereas, reduced, 'strains,', as, in, 'disuse,', are]), verbo([associated]), complemento([with, increased, sclerostin, production, and, bone, loss])]). relacion([sujeto(['However,', while, sclerostin, 'up-regulation', appears, to, be, necessary, for, the]), verbo([loss]), complemento([of, bone, with, 'disuse,', the, role, of, sclerostin, in, the, osteogenic, response, to, loading, is, more, complex])]). relacion([sujeto(['While', mice, unable, to, 'down-regulate', sclerostin, do, not]), verbo([gain]), complemento([bone, with, 'loading,', 'Sost', knockout, mice, have, an, enhanced, osteogenic, response, to, loading])]). relacion([sujeto(['The', molecular, mechanisms, by, which, osteocytes, sense, and, transduce, 'loading-related', stimuli, into, changes, in, sclerostin, expression, remain, unclear, but, include, 'several,', potentially, 'interlinked,', signalling, cascades]), verbo([involving]), complemento(['periostin/integrin,', 'prostaglandin,', estrogen, 'receptor,', 'calcium/NO', and, 'Igf', signalling])]). relacion([sujeto(['Deciphering', the, mechanisms, by, which, changes, in, the, mechanical, environment]), verbo([regulate]), complemento([sclerostin, production, may, lead, to, the, development, of, therapeutic, strategies, that, can, reverse, the, skeletal, structural, deterioration, characteristic, of, disuse, and, 'age-related', osteoporosis, and, enhance, 'bones\'', functional, adaptation, to, loading])]). relacion([sujeto(['By']), verbo([enhancing]), complemento([the, osteogenic, potential, of, the, context, in, which, individual, therapies, such, as, sclerostin, antibodies, act, it, may, become, possible, to, both, prevent, and, reverse, the, 'age-related', skeletal, structural, deterioration, characteristic, of, osteoporosis])]). relacion([sujeto(['These', 'studies,', 'however,']), verbo([have]), complemento([focused, on, a, limited, number, of, outcomes, and, have, not, examined, whether, sociodemographic, 'characteristics,', such, as, 'race/ethnicity', and, 'education,', influence, the, relationship, between, policy, change, and, health, among, sexual, minorities])]). relacion([sujeto(['Civil', union, legislation, was]), verbo([associated]), complemento([with, lower, levels, of, stigma, 'consciousness,', perceived, 'discrimination,', depressive, 'symptoms,', and, one, indicator, of, hazardous, drinking, '(', adverse, drinking, 'consequences)', for, all, sexual, minority, women])]). relacion([sujeto(['Results']), verbo([suggest]), complemento([that, policies, supportive, of, the, civil, rights, of, sexual, minorities, improve, the, health, of, all, sexual, minority, 'women,', and, may, be, most, beneficial, for, women, with, multiply, marginalized, statuses])]). relacion([sujeto(['Ketotifen']), verbo([has]), complemento([recently, been, reported, to, inhibit, the, growth, of, both, asexual, and, sexual, malaria, parasites])]). relacion([sujeto(['A', parasite, 'transporter,', 'PfgABCG2,']), verbo([has]), complemento([been, implicated, in, its, mechanism, of, action])]). relacion([sujeto(['In', 'Saccharomyces', 'cerevisiae,']), verbo([nuclear]), complemento([exosome, along, with, 'TRAMP', and, 'DRN', selectively, eliminates, diverse, aberrant, messages])]). relacion([sujeto(['Here,', using, genetic, and, molecular, approach, we, systematically, investigate, the, functional, relationship, between, 'exosome,', 'TRAMP', and, 'DRN', mechanisms, by, examining, their, relative, contributions, in, the, degradation, of, diverse, classes, of, aberrant]), verbo([nuclear]), complemento([mRNAs, generated, at, various, phases, of, mRNP, biogenesis])]). relacion([sujeto(['Our', findings]), verbo([suggest]), complemento([that, nuclear, exosome, in, association, with, the, 'TRAMP', complex, exclusively, degrades, the, transcription, 'assembly-defective', mRNPs, and, 'splice-defective', 'intron-containing', 'pre-mRNAs,', whereas, nuclear, exosome, along, with, 'DRN', solely, degrades, the, 'export-defective', messages])]). relacion([sujeto(['The', degradation, of, aberrant, 'read-through', transcripts, with, 3, '(', '\'', ')', -, 'extensions,', in, 'contrast,']), verbo([requires]), complemento([the, activity, of, 'TRAMP', and, 'DRN', together, along, with, nuclear, exosome, function])]). relacion([sujeto(['Thus,', the, profile, of, substrate, specificity, of, these]), verbo([nuclear]), complemento([decay, machines, reflects, dependency, of, the, nuclear, exosome, for, either, 'TRAMP', or, 'DRN', function, to, degrade, distinct, nuclear, mRNAs])]). relacion([sujeto(['We', propose, that, 'DRN', apparatus, may]), verbo([act]), complemento([as, a, novel, ancillary, factor, required, for, the, nuclear, exosome, function, to, degrade, specific, classes, of, aberrant, messages])]). relacion([sujeto(['In', 'agreement,', 'ABCC', was]), verbo([expressed]), complemento([at, higher, levels, than, 'ABCB'])]). relacion([sujeto(['Activation', of, the, 'cyclic-AMP', '(', 'cAMP)', dependent, protein, kinase, 'A', '(', 'PKA)', resulted, in]), verbo([increased]), complemento([rhodamine, 'efflux,', which, was, counteracted, by, the, selective, 'PKA', inhibitor, 'H89'])]). relacion([sujeto(['Although', 'serotonin,', a, physiological, modulator, of, 'cAMP/PKA', signaling, and, 'ABCB', transcription, in, 'haemocytes,', did, not, affect, basal, 'MXR', 'transport,', the, environmental, pharmaceuticals, 'fluoxetine,', 'propranolol,', and, 'carbamazepine,', which]), verbo([interact]), complemento([in, different, ways, with, the, adrenergic, and, serotoninergic, 'pathways,', were, showed, to, act, as, modulators, and, substrates, of, 'MXR-related', transporters, and, to, affect, cell, viability])]). relacion([sujeto(['While', the]), verbo([increased]), complemento(['MXR', activity, may, have, lowered, the, cytotoxic, effects, of, propranolol, and, 'carbamazepine,', the, lack, of, 'MXR', efflux, induction, by, fluoxetine, may, play, a, role, in, the, observed, cytotoxicity, of, the, compound])]). relacion([sujeto(['typhimurium)', is, globally, distributed, and]), verbo([causes]), complemento([massive, morbidity, and, mortality, in, humans, and, animals])]). relacion([sujeto([typhimurium, carries, 'Salmonella', plasmid, virulence, '(', 'spv)', 'locus,', which, is, highly]), verbo([conserved]), complemento([and, closely, related, to, bacterial, 'pathogenicity,', while, its, exact, role, in, host, immune, responses, during, infection, remains, to, be, elucidated])]). relacion([sujeto(['To', counteract, the, 'invaders,', the, host]), verbo([has]), complemento([evolved, numerous, 'strategies,', among, which, the, innate, immunity, and, autophagy, act, as, the, first, defense])]). relacion([sujeto(['Recently,', zebrafish]), verbo([has]), complemento([been, universally, accepted, as, a, valuable, and, powerful, vertebrate, model, in, analyzing, 'bacteria-host', interactions])]). relacion([sujeto(['To', investigate, whether, spv, locus]), verbo([enhances]), complemento([the, virulence, of, 'Salmonella', by, exerting, an, effect, on, the, host, early, 'defense,', zebrafish, larvae, were, employed, in, this, study])]). relacion([sujeto(['Results', indicated, that, spv, locus, could]), verbo([decrease]), complemento([the, 'LD50', of, 'S'])]). relacion([sujeto([typhimurium, to, zebrafish, 'larvae,', accelerate, the, reproduction, and, dissemination, of, bacteria, by]), verbo([inhibiting]), complemento([the, function, of, neutrophils, and, macrophages])]). relacion([sujeto(['These', findings]), verbo([suggested]), complemento([the, virulence, of, spv, locus, involving, in, suppressing, host, innate, immune, responses, for, the, first, 'time,', which, shed, new, light, on, the, role, of, spv, operon, in, 'Salmonella', pathogenicity])]). relacion([sujeto(['Several', gill, claudin, '(', 'Cldn)', tight, junction, proteins, in, 'Japanese', medaka, are]), verbo([regulated]), complemento([by, salinity, '(', cldn10, paralogs, and, 'cldn28b),', while, others, are, constitutively, expressed, '(', 'cldn27a,', cldn28a, and, 'cldn30c)'])]). relacion([sujeto(['The', role, of, the, endocrine, system, in, this, regulation]), verbo([has]), complemento([yet, to, be, understood])]). relacion([sujeto([ncc2b, and, cftr, were, used, as, markers, of, specific, ionocytes]), verbo([associated]), complemento([with, 'freshwater-', and, 'seawater-acclimation,', respectively])]). relacion([sujeto(['Prolactin', had, a, 'concentration-dependent', 'effect,']), verbo([decreasing]), complemento([expression, of, cftr, '(', 1, 'μgmL(-1),', 2.2, -, 'fold)', while, increasing, ncc2b, '(', from, 0.1, 'μgmL(-1),', 6, -, 7, -, 'fold)'])]). relacion([sujeto(['A', combination, experiment, with, both, hormones, showed, that, they]), verbo([act]), complemento([in, synergy, on, cldn28b, and, have, an, additive, effect, on, 'cftr,', 'ncc2b,', cldn10c, and, cldn10f])]). relacion([sujeto(['Our', results, showed, that, cortisol, and, prolactin, are, essential, to]), verbo([maintain]), complemento([the, expression, of, specific, branchial, claudins])]). relacion([sujeto(['This', work, also]), verbo([provides]), complemento([evidence, that, both, hormones, act, directly, on, gill, of, medaka, to, modulate, determinants, of, paracellular, ion, movement])]). relacion([sujeto(['This']), verbo([finding]), complemento([is, additionally, verified, and, explained, by, 'MD', simulations, which, demonstrate, that, the, '(', 1, ')', 'HO(2)', and, '(', 1, ')', 'HO(6)', hydroxyl, groups, of, the, constituting, glucose, units, act, as, 'hydrogen-bond', donors, to, 'water,', while, the, '(', 1, ')', 'HO(3)', groups, behave, exclusively, as, 'hydrogen-bond', acceptors, from, water, and, donate, hydrogen, to, their, 'intra-chain', neighbors, 'O(5)'])]). relacion([sujeto(['The', goals, of, this, article, are, to, review, the, pertussis, cocooning, 'strategy,', which]), verbo([has]), complemento([been, recommended, in, 'France', since, 2004, to, protect, infants, not, yet, vaccinated, from, becoming, infected, by, vaccinating, their, immediate, 'entourage,', and, to, present, room, for, improvement])]). relacion([sujeto(['The', analysis, of, the, literature, between, 2004, and, 2015, shows, that, pertussis, vaccine, coverage, in, new, parents, is, lower, than, 50, '%', and, that, attempts, that]), verbo([have]), complemento([already, been, implemented, to, increase, it, are, effective])]). relacion([sujeto(['Pertussis', vaccine, coverage, improvement]), verbo([requires]), complemento([all, health, actors, to, collaborate, and, be, trained, in, informing, and, motivating, parents, to, get, vaccinated, 'before,', during, and, after, pregnancy, '(', the, parents, then, will, act, as, relays, to, their, 'relatives);', generalization, in, maternity, wards, of, systematic, checking, of, the, vaccination, 'card;', extension, to, the, midwives, of, the, right, to, prescribe, and, administer, pertussis, vaccine, to, 'spouses;', vaccination, facilitation, in, maternity, wards, with, the, support, of, health, organizations])]). relacion([sujeto(['Pregnancy', is, the, ideal, period, to]), verbo([promote]), complemento([pertussis, vaccination])]). relacion([sujeto(['The', laboratory, of, genetics, and, physiology, 2, '(', 'LGP2)', is, a, member, of, retinoic, 'acid-inducible', gene, 'I', '(', 'RIG-I)-like', receptors, '(', 'RLR', 'receptors),', which, may]), verbo([participate]), complemento([in, the, immune, regulation, process])]). relacion([sujeto(['The', role, of, 'LGP2', on]), verbo([modulating]), complemento([signaling, was, 'ambiguous,', some, researchers, suggested, that, the, regulation, mechanism, of, 'LGP2', to, melanoma, 'differentiation-associated', gene, 5, '(', 'MDA5)', and, retinoic, acid, inducible, 'gene-I', '(', 'RIG-I)', were, different])]). relacion([sujeto(['Comparative', genomic, analysis, showed, that, the, evolution, of, 'LGP2', in, mammals, was, more]), verbo([conserved]), complemento([than, it, in, fish])]). relacion([sujeto(['The', mmLGP2, was, ubiquitously]), verbo([expressed]), complemento([in, the, tested, miiuy, croaker, tissues, and, the, expressions, were, significantly, upregulated, after, stimulation, with, 'poly(I:C),', indicating, that, 'LGP2', might, participate, in, the, immune, 'response,', especially, antiviral, immunity])]). relacion([sujeto(['The', overexpression, of, mmLGP2, can]), verbo([activate]), complemento(['ISRE,', but, cannot, activate, 'NF-κB', luciferase, 'reporter,', implying, that, mmLGP2, might, act, as, a, positive, regulator, in, immune, responses, through, activating, 'ISRE', to, induce, the, expression, of, 'IFN'])]). relacion([sujeto(['Soon', after, the, emergence, of, 2009, pandemic, 'H1N1,', the, first, outbreaks, in, breeder, turkey, operations, were]), verbo([reported]), complemento([that, implicated, 'human-to-turkey', transmission])]). relacion([sujeto(['In', addition, to, raising, concerns, over, biosecurity, and, vaccine, 'failures,', these, cases, once, again, raise, the, issue, of, whether, turkeys]), verbo([have]), complemento([the, potential, to, act, as, a, bridge, species, to, generate, novel, influenza, 'A', virus, reassortants, with, public, health, implications])]). relacion([sujeto([1.184, ',', 'hCBR1)', is, shown, to, efficiently]), verbo([act]), complemento([as, aldehyde, reductase, on, glutathionylated, 'alkanals,', namely, 3, -, 'glutathionyl-4-hydroxynonanal', '(', 'GSHNE),', 3, -, 'glutathionyl-nonanal,', 3, -, 'glutathionyl-hexanal', and, 3, -, 'glutathionyl-propanal'])]). relacion([sujeto(['Mass', spectrometry, analysis]), verbo([reveals]), complemento([the, ability, of, hCBR1, to, reduce, 'GSHNE', to, the, corresponding, 'GS-dihydroxynonane', '(', 'GSDHN)', and, at, the, same, time, to, catalyze, the, oxidation, of, the, hemiacetal, form, of, 'GSHNE,', generating, the, 3, -, 'glutathionylnonanoic-δ-lactone'])]). relacion([sujeto(['These', results, evidence, the, potential, of, hCBR1]), verbo([acting]), complemento([on, 'GSHNE', to, accomplish, a, dual, 'role,', both, in, terms, of, 'HNE', detoxification, 'and,', through, the, production, of, 'GSDHN,', in, terms, of, involvement, into, the, signalling, cascade, of, the, cellular, inflammatory, response])]). relacion([sujeto(['Significant', heterogeneity, between, different, tumors]), verbo([prevents]), complemento([the, discovery, of, cancer, driver, 'genes,', especially, in, a, 'patient-specific', manner])]). relacion([sujeto(['The', prioritized, 'mutation-driver', genes]), verbo([act]), complemento([as, tumor, suppressor, genes, and, inhibit, cell, proliferation, and, migration])]). relacion([sujeto(['In', 'addition,', the, 'loss-of-function', effect, of, the, 'patient-specific', mutations]), verbo([promoted]), complemento([cell, proliferation, and, migration])]). relacion([sujeto(['Of', 'note,', the, 'HNF1A', 'S247T', mutation, significantly, reduced, the, 'HNF1A', transcriptional, activity, for, hepatocyte]), verbo([nuclear]), complemento([factor, 4, alpha, '(', 'HNF4A)', but, did, not, disrupt, nuclear, localization, of, 'HNF1A'])]). relacion([sujeto(['The', results]), verbo([provide]), complemento([evidence, for, supporting, the, validity, of, our, proposed, 'multi-omics', 'strategy,', which, supplies, a, new, avenue, for, prioritizing, 'mutation-drivers', towards, personalized, cancer, therapy])]). relacion([sujeto(['Seven', myths]), verbo([associated]), complemento([with, machine, learning, and, big, data, are, then, 'presented,', with, the, aim, of, managing, expectation, of, machine, learning, amongst, clinical, chemists])]). relacion([sujeto(['The', myths, are, illustrated, with, four, examples, investigating, the, relationship, between, biomarkers, in, liver, function, 'tests,']), verbo([enhanced]), complemento([laboratory, prediction, of, hepatitis, virus, 'infection,', the, relationship, between, bilirubin, and, white, cell, 'count,', and, the, relationship, between, red, cell, distribution, width, and, laboratory, prediction, of, anaemia])]). relacion([sujeto(['Perinatal', network, the, &, 'quot;Security', 'birth"', 'Pays', de, la, 'Loire', '(', 'RSN),', in, collaboration, with, the, regional, network, &, 'quot;Sexual', 'health"', '(', 'RRSS)', organized, a, satisfaction, survey, in, 2014, &, 'nbsp;among', women, who, had, an]), verbo([induced]), complemento([abortion, in, the, centers, in, 'Pays', de, la, 'Loire'])]). relacion([sujeto(['Data', were, collected, on, the, civil, 'status,', the, care, pathway, to, get, to, the, abortion, 'center,', features, centers, and, professionals, 'met,']), verbo([acts]), complemento([anesthesia, and, end, of, 'abortion,', wait, times, and, overall, satisfaction, of, women])]). relacion([sujeto(['Finally,', 12.6, &, 'nbsp;%', of, women]), verbo([reported]), complemento([for, improvement, with, clear, remarks])]). relacion([sujeto(['Five', areas, for, improvement]), verbo([have]), complemento([been, proposed, to, the, 'care-givers', of, the, centers])]). relacion([sujeto(['Current', 'practices,', medications, used, and, statistics, relating, to, prescription, frequency, and, death, rates, from, the]), verbo([participating]), complemento(['States', are, briefly, discussed])]). relacion([sujeto(['The', highly]), verbo([conserved]), complemento(['RAS-mitogen', activated, protein, kinase, '(', 'MAPK)', signaling, pathway, is, involved, in, a, wide, range, of, cellular, processes, including, 'differentiation,', 'proliferation,', and, survival])]). relacion([sujeto(['Since', the, pioneering, study]), verbo([reporting]), complemento([that, 'let-7', miRNA, acted, as, tumor, suppressor, by, repressing, the, 'RAS', 'oncogene,', growing, evidence, has, suggested, the, importance, of, miRNAs, targeting, the, 'RAS-MAPK', in, oncogenesis])]). relacion([sujeto(['MiRNAs', alterations, in, human, cancers, may]), verbo([act]), complemento([as, a, rheostat, of, the, oncogenic, 'RAS', signal, that, is, often, amplified, as, cancers, progress])]). relacion([sujeto(['However,', specific, mechanisms]), verbo([leading]), complemento([to, miRNAs, deregulation, and, their, functional, consequences, in, cancer, are, far, from, being, fully, elucidated])]). relacion([sujeto(['In', this, 'review,', we]), verbo([provide]), complemento([an, 'experimental-validated', map, of, 'RAS-MAPK', oncomiRs, and, tumor, suppressor, miRNAs, from, transmembrane, receptor, to, downstream, 'ERK', proteins])]). relacion([sujeto(['Buffalo']), verbo([act]), complemento([as, reservoirs, of, 'M'])]). relacion([sujeto([&, 'nbsp;bovis,', the, causative, agent, of, bovine, tuberculosis, '(', 'BTB),', which, can]), verbo([have]), complemento([major, 'economic,', ecological, and, public, health, impacts, through, the, risk, of, infection, to, other, wildlife, 'species,', livestock, and, surrounding, communities])]). relacion([sujeto(['Herds', experiencing, more, intensive, and, frequent, captures, showed, reduced, per, capita, disease, transmission, risk, and, less]), verbo([increase]), complemento([in, herd, prevalence, over, time])]). relacion([sujeto(['Disease', hot, spots, did, not, expand, spatially, over, 'time,', and, 'BTB', prevalence, in, all, but, the, hot, spot, areas, was]), verbo([maintained]), complemento([between, 10, '%', and, 15, '%', throughout, the, study, period])]). relacion([sujeto(['Our', data]), verbo([suggest]), complemento([that, 'HiP\'s', test, and, cull, programme, was, effective, at, reducing, 'BTB', transmission, in, 'buffalo,', with, capture, effort, and, interval, found, to, be, the, crucial, components, of, the, programme])]). relacion([sujeto(['Our', results]), verbo([suggest]), complemento([that, 'speed-of-processing', skills, in, 'preschool-age', children, are, reflected, in, functional, activation, and, connectivity, during, story, listening, and, may, act, as, a, biomarker, for, future, academic, abilities])]). relacion([sujeto(['Several', studies, showed, a, potential, 'anti-tumor', role, for, 'cannabinoids,', by]), verbo([modulating]), complemento([cell, signaling, pathways, involved, in, cancer, cell, 'proliferation,', 'chemo-resistance', and, migration])]). relacion([sujeto(['Cannabidiol', '(', 'CBD)', was, previously, noted, in, multiple, myeloma, '(', 'MM),', both, alone, and, in, synergy, with, the, proteasome, inhibitor, 'bortezomib,', to]), verbo([induce]), complemento([cell, death])]). relacion([sujeto(['In', other, type, of, human, 'cancers,', the, combination, of, 'CBD', with, 'Δ9-tetrahydrocannabinol', '(', 'THC)', was]), verbo([found]), complemento([to, act, synergistically, with, other, chemotherapeutic, drugs, suggesting, their, use, in, combination, therapy])]). relacion([sujeto(['We']), verbo([found]), complemento([that, 'CBD', and, 'THC,', mainly, in, 'combination,', were, able, to, reduce, cell, viability, by, inducing, 'autophagic-dependent', necrosis])]). relacion([sujeto(['Furthermore,', since, the, 'immuno-proteasome', is, considered, a, new]), verbo([target]), complemento([in, 'MM', and, also, since, carfilzomib, '(', 'CFZ)', is, a, new, promising, 'immuno-proteasome', inhibitor, that, creates, irreversible, adducts, with, the, β5i, subunit, of, 'immuno-proteasome,', we, evaluated, the, effect, of, 'CBD', and, 'THC', in, regulating, the, expression, of, the, β5i, subunit, and, their, effect, in, combination, with, 'CFZ'])]). relacion([sujeto(['Herein,', we, also]), verbo([found]), complemento([that, the, 'CBD', and, 'THC', combination, is, able, to, reduce, expression, of, the, β5i, subunit, as, well, as, to, act, in, synergy, with, 'CFZ', to, increase, 'MM', cell, death, and, inhibits, cell, migration])]). relacion([sujeto(['Systemic', lupus, erythematosus, '(', 'SLE)', is, a, severe, autoimmune, disease, that]), verbo([causes]), complemento(['multiple-organ', dysfunction, mainly, affecting, women, in, their, childbearing, years])]). relacion([sujeto(['Type', 'I', 'IFN', synthesis, is, usually]), verbo([triggered]), complemento([by, 'viruses,', and, its, production, is, tightly, regulated, and, limited, in, time, in, health, individuals])]). relacion([sujeto(['However,', many, patients, with, systemic, autoimmune, diseases, including, 'SLE']), verbo([have]), complemento([signs, of, aberrant, production, of, type, 'I', interferon, '(', 'IFN)', and, display, an, increased, expression, of, 'IFN-inducible', genes])]). relacion([sujeto(['Continuous', type, 'I', 'IFNs', derived, from]), verbo([activated]), complemento([plasmacytoid, dendritic, cells, '(', 'pDCs)', by, interferogenic, immune, complexes, '(', 'ICs)', and, migration, of, these, cells, to, tissues, both, break, immune, tolerance, and, promote, an, 'on-going', autoimmune, reaction, in, human, body])]). relacion([sujeto(['Anti-IFN-α', monoclonal, antibodies, in, 'SLE', patients, were, recently]), verbo([reported]), complemento([and, is, now, being, investigated, in, phase, 'II', clinical, trails])]). relacion([sujeto(['Possible', mechanisms, behind, the, dysregulated, type, 'I', 'IFN', system, in, 'SLE', and, how, they, contribute, to, the, development, of, an, autoimmune, 'process,', and]), verbo([act]), complemento([as, a, biomarker, and, therapeutic, target, will, be, reviewed])]). relacion([sujeto(['Because', of]), verbo([increased]), complemento([law, enforcement, and, subsequent, media, 'attention,', methamphetamine, users, appear, in, the, 'public\'s', imagination, as, 'diseased,', 'zombie-like', 'White', trash])]). relacion([sujeto(['Specifically,', we, presented, participants, with, images, from, the, 'Faces', of, 'Meth', and, the, 'Montana', 'Meth', 'Project', campaigns, to]), verbo([stimulate]), complemento([discussion])]). relacion([sujeto(['We']), verbo([found]), complemento([that, participants, believed, these, ads, did, not, reflect, their, personal, experiences, and, consequently, were, ineffective, at, curtailing, their, own, methamphetamine, use])]). relacion([sujeto(['Findings']), verbo([suggest]), complemento([that, there, are, unintended, consequences, to, 'inauthentic/dramatic', imagery])]). relacion([sujeto(['Consequently,', overly, stigmatizing, portraits, of, users, may]), verbo([act]), complemento([as, barriers, to, desistence])]). relacion([sujeto(['The', findings]), verbo([have]), complemento([implications, for, designing, 'anti-methamphetamine', campaigns])]). relacion([sujeto(['Social', class, is, a, robust, predictor, of, 'health,', with, risk, for, disease, and, mortality]), verbo([increasing]), complemento([towards, the, lower, end, of, the, socioeconomic, '(', 'SES)', spectrum])]). relacion([sujeto(['While', certain, psychological, 'characteristics,', such, as, high, sense, of, 'control,', can, protect, 'low-SES', individuals, from, adverse, health, 'outcomes,', very, few, studies]), verbo([have]), complemento([investigated, the, biological, mechanisms, underlying, these, relationships])]). relacion([sujeto(['Next,', we, tested, whether, individual, differences, in, cortisol, secretion, would]), verbo([act]), complemento([as, a, mechanism, by, which, 'SES', and, perceived, control, influenced, physical, health])]). relacion([sujeto(['In', a, large, national, sample, from, the, 'Midlife', in, the, 'United', 'States', '(', 'MIDUS)', 'survey,', we]), verbo([found]), complemento([that, 'SES', interacted, with, perceived, control, in, predicting, morning, cortisol, 'levels,', cortisol, 'slopes,', number, of, physical, 'symptoms,', and, severity, of, physical, symptoms])]). relacion([sujeto(['Specifically,', 'SES', disparities, in, these, health, outcomes, were, more, pronounced, among, individuals]), verbo([reporting]), complemento([low, levels, of, perceived, control, than, among, individuals, endorsing, high, levels, of, perceived, control])]). relacion([sujeto(['Further,', we]), verbo([found]), complemento([that, a, flatter, cortisol, slope, mediated, the, link, between, lower, 'SES', and, greater, number, and, severity, of, physical, symptoms, for, those, individuals, who, reported, lower, levels, of, perceived, 'control,', but, not, for, individuals, reporting, higher, levels, of, perceived, control])]). relacion([sujeto(['These', findings]), verbo([suggest]), complemento([that, perception, of, greater, control, may, act, as, a, buffer, against, the, effect, of, low, 'SES', on, 'health-related', physiological, processes])]). relacion([sujeto(['Evidence']), verbo([suggests]), complemento([the, putative, human, pheromone, 'Δ4,16-androstadien-3-one', '(', 'androstadienone),', a, natural, component, of, human, 'sweat,', increases, attention, to, emotional, information, when, passively, 'inhaled,', even, in, minute, amounts])]). relacion([sujeto(['However,', the, neural, mechanisms, underlying, 'androstadienone\'s', impact, on, the, perception, of, emotional, stimuli]), verbo([have]), complemento([not, been, clarified])]). relacion([sujeto(['These', models, indicated, that, emotional, images]), verbo([increased]), complemento([the, drive, from, 'V1', to, the, amygdala, during, the, control, session])]). relacion([sujeto(['With', androstadienone, 'present,', this, drive, to, amygdala, was]), verbo([decreased]), complemento([specifically, for, positive, 'images,', which, drove, downstream, increases, in, orbitofrontal, and, prefrontal, activity])]). relacion([sujeto(['This', evidence]), verbo([suggests]), complemento([that, androstadienone, may, act, as, a, chemical, signal, to, increase, attention, to, positively, valenced, information, via, modifications, to, amygdala, connectivity])]). relacion([sujeto(['The', obtained, 'TaOx@PFC-PEG', nanoparticles, on, one, hand, can, absorb, 'X-ray', by, 'TaOx', to, concentrate, radiation, energy, within, tumor, 'cells,', on, the, other, hand, after, saturating, 'PFC', with, oxygen, will]), verbo([act]), complemento([as, an, oxygen, reservoir, to, gradually, release, oxygen, and, improve, tumor, oxygenation])]). relacion([sujeto(['As', the, 'result,', remarkably]), verbo([enhanced]), complemento(['in vivo', 'RT', treatment, is, achieved, with, 'TaOx@PFC-PEG', nanoparticles, in, our, mouse, tumor, model, experiments])]). relacion([sujeto(['Our', work, thus, presents, a, new, nanotechnology, strategy, to]), verbo([enhance]), complemento(['RT-induced', tumor, treatment, by, simultaneously, concentrating, radiation, energy, within, tumors, and, improving, tumor, 'oxygenation,', using, one, multifunctional, agent])]). relacion([sujeto(['Homeodomain', proteins, are, evolutionary]), verbo([conserved]), complemento([proteins, present, in, the, entire, eukaryote, kingdom])]). relacion([sujeto(['They']), verbo([execute]), complemento([functions, that, are, essential, for, 'life,', both, in, developing, and, adult, organisms])]). relacion([sujeto(['Most', homeodomain, proteins]), verbo([act]), complemento([as, transcription, factors, and, bind, 'DNA', to, control, the, activity, of, other, genes])]). relacion([sujeto(['In', contrast, to, their, similar, 'DNA']), verbo([binding]), complemento(['specificity,', homeodomain, proteins, execute, highly, diverse, and, 'context-dependent', functions])]). relacion([sujeto(['Several', 'factors,', including, genome, 'accessibility,', 'DNA', 'shape,', combinatorial]), verbo([binding]), complemento([and, the, ability, to, interact, with, many, transcriptional, 'partners,', diversify, the, activity, of, homeodomain, proteins, and, culminate, in, the, activation, of, highly, 'dynamic,', 'context-specific', transcriptional, programs])]). relacion([sujeto(['The', uptaken, 'DNA', can, integrate, into, host, cell, genomes, and, can, be]), verbo([transcribed]), complemento([and, translated, into, proteins])]). relacion([sujeto(['They', can, also]), verbo([cause]), complemento([chromosomal, damage, and, karyotype, alterations])]). relacion([sujeto(['However,', whether, extracellular, cfNAs, that, are]), verbo([released]), complemento([into, circulation, from, dying, cells, as, a, consequence, of, normal, physiology, have, any, functional, significance, has, not, been, explored])]). relacion([sujeto(['A', recent, study]), verbo([has]), complemento([demonstrated, that, circulating, cfNAs, have, the, ability, to, cause, 'DNA', damage, and, mutagenesis, by, illegitimately, integrating, into, healthy, cells, of, the, 'body,', thereby, acting, as, mobile, genetic, elements])]). relacion([sujeto(['Fluorescently-labeled', cfNAs, isolated, from, sera, of, cancer, patients, and, healthy, volunteers, were, shown, to, be, readily, taken, up, by, host, cells, followed, by, activation, of, a, 'DNA-damage-repair-response', which]), verbo([led]), complemento([their, large, scale, integration, into, the, host, cell, genomes])]). relacion([sujeto(['The', latter]), verbo([caused]), complemento([dsDNA, breaks, and, apoptosis, in, cells, in, vitro, and, in, those, of, vital, organs, when, injected, intravenously, into, mice])]). relacion([sujeto(['This', study]), verbo([suggests]), complemento([that, circulating, extracellular, cfNAs, act, as, physiological, continuously, arising, 'DNA', mutagens, with, implications, for, 'ageing,', cancer, and, a, host, of, other, degenerative, human, pathologies])]). relacion([sujeto(['Calcium', entry, via, voltage, gated, calcium, channels]), verbo([mediates]), complemento([a, wide, range, of, physiological, 'functions,', whereas, calcium, channel, dysregulation, has, been, associated, with, numerous, pathophysiological, conditions])]). relacion([sujeto(['There', are, myriad, cell, signaling, pathways, that]), verbo([act]), complemento([on, voltage, gated, calcium, channels, to, fine, tune, their, activities, and, to, regulate, their, cell, surface, expression])]). relacion([sujeto(['The', inflammatory, response]), verbo([requires]), complemento([coordinated, activation, of, both, transcription, factors, and, chromatin, to, induce, transcription, for, defense, against, pathogens, and, environmental, insults])]). relacion([sujeto([&, 'nbsp;We', identified, 'H3', serine, 28, phosphorylation, '(', 'H3S28ph)', as, the, principal, 'stimulation-dependent', histone, modification, and, observed, its, enrichment, at]), verbo([induced]), complemento([genes, in, mouse, macrophages, stimulated, with, bacterial, lipopolysaccharide])]). relacion([sujeto(['Cell-free', transcription, assays, demonstrated, that, 'H3S28ph', directly]), verbo([promotes]), complemento(['p300/CBP-dependent', transcription])]). relacion([sujeto(['Further,', 'MSKs', can]), verbo([activate]), complemento([both, 'signal-responsive', transcription, factors, and, the, chromatin, template, with, additive, effects, on, transcription])]). relacion([sujeto(['Our', results]), verbo([suggest]), complemento([that, 'MSKs', incorporate, upstream, signaling, inputs, and, control, multiple, downstream, regulators, of, inducible, transcription])]). relacion([sujeto(['Why', do, forest, productivity, and, biomass, decline, with, 'elevation?', 'To', address, this, 'question,', research, to, date, generally]), verbo([has]), complemento([focused, on, correlative, approaches, describing, changes, in, woody, growth, and, biomass, with, elevation])]). relacion([sujeto(['Rather', than, a, gradual, linear, decline, in, 'productivity,', there, is, some, limited, but, nonconclusive, evidence, of, a, sharp, transition, in, 'NPP', between, submontane, and, montane, 'forests,', which, may, be]), verbo([caused]), complemento([by, cloud, immersion, effects, within, the, cloud, forest, zone])]). relacion([sujeto(['Our', data, demonstrate, the, potential, of, whole, carbon, budget, perspectives, to]), verbo([provide]), complemento([a, deeper, understanding, of, controls, on, ecosystem, functioning, and, carbon, cycling])]). relacion([sujeto([is, a, significant]), verbo([cause]), complemento([of, disease, for, both, humans, and, 'wildlife,', with, wild, birds, adapted, to, urban, environments, having, different, opportunities, for, pathogen, 'exposure,', 'infection,', and, transmission, compared, to, their, natural, conspecifics])]). relacion([sujeto(['The', prevalence, of, 'Salmonella', shedding, by, ibises, significantly]), verbo([decreased]), complemento([as, the, percent, of, 'Palustrine', emergent, wetlands, and, herbaceous, grasslands, 'increased,', and, increased, as, the, proportion, of, 'open-developed', land, types, '(', e])]). relacion([sujeto(['parks,', 'lawns,', golf, 'courses)', 'increased,']), verbo([suggesting]), complemento([that, natural, ecosystem, land, cover, types, supported, birds, with, a, lower, prevalence, of, infection])]). relacion([sujeto(['Together,', our, results, indicate, that, ibises, are, good, indicators, of, salmonellae, strains, circulating, in, their, environment, and, they]), verbo([have]), complemento([both, the, potential, and, opportunity, to, transmit, salmonellae, to, people])]). relacion([sujeto(['Finally,', they, may]), verbo([act]), complemento([as, salmonellae, carriers, to, natural, environments, where, other, more, 'highly-susceptible', groups, '(', 'nestlings)', may, be, detrimentally, affected])]). relacion([sujeto(['Understanding', the, determinants, of, the, 'public\'s', behavioral, response, is, crucial, for, devising, public, health, 'campaigns,']), verbo([providing]), complemento([information, to, parametrize, mathematical, 'models,', and, ultimately, limiting, disease, spread])]). relacion([sujeto(['While', other, reviews]), verbo([have]), complemento([qualitatively, analyzed, the, body, of, work, on, demographic, determinants, of, 'health-protective', 'behavior,', this, 'meta-analysis', quantitatively, combines, the, results, from, 85, publications, to, determine, the, global, relationship, between, gender, and, 'health-protective', behavioral, response])]). relacion([sujeto(['It', is, possible, that, factors, other, than, 'pharmaceutical/non-pharmaceutical', status, not, included, in, this, analysis]), verbo([act]), complemento([as, moderators, of, this, relationship])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([an, inherent, difference, in, how, men, and, women, respond, to, epidemic, and, pandemic, respiratory, infectious, diseases])]). relacion([sujeto(['This', information, can, be, used, to]), verbo([target]), complemento([specific, groups, when, developing, 'non-pharmaceutical', public, health, campaigns, and, to, parameterize, epidemic, models, incorporating, demographic, information])]). relacion([sujeto(['An', 11, -, 'year-old', healthy, girl, was, noted, to]), verbo([have]), complemento(['intermittent,', 'spontaneous,', and, bilateral, hemolacria, of, 14, 'months\'', duration])]). relacion([sujeto(['This']), verbo([report]), complemento([draws, attention, to, this, unusual, and, often, concerning, clinical, entity])]). relacion([sujeto(['The', case]), verbo([report]), complemento([is, in, compliance, with, the, 'Health', 'Insurance', 'Portability', and, 'Accountability', 'Act'])]). relacion([sujeto(['Global', population, aging]), verbo([has]), complemento([raised, academic, interest, in, successful, aging, to, a, public, policy, priority])]). relacion([sujeto(['However,', their, aging, status]), verbo([has]), complemento([never, been, examined, using, a, comprehensive, multidimensional, successful, aging, definition])]). relacion([sujeto(['Here,', we, examine, the, successful, aging, 'literature,', propose, a, successful, aging, definition, based, on, this, 'literature,', present, evidence, which]), verbo([suggests]), complemento([masters, athletes, could, be, considered, exemplars, of, successful, aging, according, to, the, proposed, 'definition,', and, list, future, experimental, research, directions])]). relacion([sujeto(['Despite', the, exercise, 'benefits,', disparities, among, diverse, older, adults, continue, to, exist, where, 'African', 'American', women]), verbo([have]), complemento([the, lowest, percentage, of, any, population, group, in, meeting, national, recommended, activity, guidelines])]). relacion([sujeto(['Although', most, women]), verbo([reported]), complemento([being, 'active,', only, three, participants, met, the, 'Healthy', 'People', 2020, guidelines, for, aerobic, and, 'muscle-strengthening', 'activities,', while, two, individuals, were, inactive])]). relacion([sujeto(['While', muscle, force, gradually]), verbo([increased]), complemento([throughout, the, training, period, '(', 'p<0'])]). relacion([sujeto([5, ')', ',', significant]), verbo([increase]), complemento([in, tendon, stiffness, was, observed, after, 8, weeks, '(', 'p<0'])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, masters, runners, are, not, spared, from, the, 'age-associated', decline, in, postural, stability, and, may, benefit, from, specific, balance, training])]). relacion([sujeto(['Absolute', average, power, was]), verbo([maintained]), complemento([from, 'C1-C3,', but, decreased, '(', 'p<'])]). relacion([sujeto(['Absolute', peak, power]), verbo([decreased]), complemento([between, 'C1-C2', '(', 'p<'])]). relacion([sujeto([1, ')', ',', was, similar, between, 'C2-C3,', and]), verbo([decreased]), complemento([in, 'C4', '(', 'p<'])]). relacion([sujeto(['Relative', '(', to, body, 'weight)', average, and, peak, power]), verbo([decreased]), complemento([between, 'C1-C2', '(', 'p<'])]). relacion([sujeto([1, ')', ',', was, similar, between, 'C2-C3,', and]), verbo([decreased]), complemento([in, 'C4', '(', 'p<'])]). relacion([sujeto(['Average', velocity, was, similar, between, 'C1', and, 'C2,', but]), verbo([decreased]), complemento([in, 'C3', '(', 'p<'])]). relacion([sujeto(['To', determine, how, care, home, managers, negotiate, the, conflict, between]), verbo([maintaining]), complemento([a, safe, environment, while, enabling, the, autonomy, of, residents, with, dementia])]). relacion([sujeto(['There', were, three, areas, in, which, care, home, staff]), verbo([reported]), complemento([balancing, safety, and, risk, against, the, individual, needs, of, residents])]). relacion([sujeto(['First,', the, physical, environment, created, a, tension, between, safety, and, accessibility, to, the, outside, 'world,', which, meant, that, care, homes]), verbo([provided]), complemento([highly, structured, or, limited, access, to, outdoor, space])]). relacion([sujeto(['Second,', care, home, managers, reflected, a, balancing]), verbo([act]), complemento([between, an, 'individual\'s', autonomy, and, the, need, to, protect, their, 'residents\'', dignity])]). relacion([sujeto(['Managing', individual, needs, while]), verbo([maintaining]), complemento([a, safe, care, home, environment, clearly, is, a, constant, dynamic, interpersonal, process, of, negotiating, and, balancing, competing, interests, for, care, home, managers])]). relacion([sujeto(['The', 'energy-dependent', cross, section, of, the, ^, '{', 7, '}', 'Be(n,α)^{4}He', 'reaction,', of, interest, for, the, 'so-called', cosmological, lithium, problem, in, big, bang, 'nucleosynthesis,']), verbo([has]), complemento([been, measured, for, the, first, time, from, 10, &, 'nbsp;meV', to, 10, &, 'nbsp;keV', neutron, energy])]). relacion([sujeto(['The', challenges, posed, by, the, short, 'half-life', of, ^, '{', 7, '}', 'Be', and, by, the, low, reaction, cross, section]), verbo([have]), complemento([been, overcome, at, n_TOF, thanks, to, an, unprecedented, combination, of, the, extremely, high, luminosity, and, good, resolution, of, the, neutron, beam, in, the, new, experimental, area, '(', 'EAR2)', of, the, n_TOF, facility, at, 'CERN,', the, availability, of, a, sufficient, amount, of, chemically, pure, ^, '{', 7, '}', 'Be,', and, a, specifically, designed, experimental, setup])]). relacion([sujeto(['Coincidences', between, the, two, alpha, particles]), verbo([have]), complemento([been, recorded, in, two, 'Si-^{7}Be-Si', arrays, placed, directly, in, the, neutron, beam])]). relacion([sujeto(['The', present, results, are, 'consistent,', at, thermal, neutron, 'energy,', with, the, only, previous, measurement, performed, in, the, 1960, s, at, a]), verbo([nuclear]), complemento([reactor])]). relacion([sujeto(['The', energy, dependence]), verbo([reported]), complemento([here, clearly, indicates, the, inadequacy, of, the, cross, section, estimates, currently, used, in, 'BBN', calculations])]). relacion([sujeto(['Exploration', of, interfacial, hydration, networks, of, zwitterion, and, nonionized, trialanine]), verbo([has]), complemento([been, performed, using, 'DFT-M062X', quantum, chemical, computations, explicitly, considering, up, to, 41, water, molecules])]). relacion([sujeto(['The', 'step-by-step', water, molecules, peptide, 'surrounding,', carried, out, for, unfolded, extended, '(', 'β),', polyproline, 'II', '(', 'PPII)', conformations]), verbo([reveals]), complemento([the, crucial, importance, of, explicit, solvent, effects, in, stabilizing, the, zwitterion, form, and, the, 'left-handed', 'PPII-helix', ubiquitously, found, at, room, temperature, for, short, polyalanines])]). relacion([sujeto(['For', the, β, '→', 'PPII', 'transformation,', the, two, components, of, free, 'Gibbs', energy]), verbo([act]), complemento([in, the, opposite, 'direction;', 'thus,', it, is, favored, by, enthalpy, but, not, by, entropy])]). relacion([sujeto(['These', findings, agree, with, experimental, data, that]), verbo([report]), complemento([an, equilibrium, between, these, conformers, modulated, by, temperature])]). relacion([sujeto(['The', enthalpic, preference, of, the, 'PPII']), verbo([has]), complemento([electrostatic, origin, and, it, is, owing, to, a, more, favorable, interaction, of, dipole, of, each, peptidic, residue, with, water, dipole, of, 'H-bonded', molecules])]). relacion([sujeto(['Owing', to, their, ability, to]), verbo([act]), complemento([as, 'light-harvesting', 'scaffolds,', 'porphyrin-containing', 'metal-organic', frameworks, '(', 'MOFs)', are, in, the, forefront, of, research, on, the, application, of, highly, ordered, molecular, materials, to, problems, in, 'solar-energy', conversion])]). relacion([sujeto(['The', change, in, dimensionality, of, the, framework, is, confirmed, by, a]), verbo([decrease]), complemento([in, the, film, 'thickness,', the, magnitude, of, which, is, in, agreement, with, crystallographic, parameters, for, related, bulk, materials])]). relacion([sujeto(['Furthermore,', 'NMR', spectroscopy, performed, on, the, digested, sample]), verbo([suggests]), complemento([a, similar, change, in, geometry, is, achieved, in, bulk, 'MOF', samples])]). relacion([sujeto(['The']), verbo([decreased]), complemento([distance, between, the, porphyrin, chromophores, in, the, 2, 'D', 'MOF', film, compared, to, the, 3, 'D', film, results, in, enhanced, energy, transfer, through, the, film])]). relacion([sujeto(['The', extent, of, energy, transport, was, probed, by, assembling, 'MOF', thin, film, where, the, outermost, layers, are, palladium, porphyrin, '(', 'P2)', 'units,', which]), verbo([act]), complemento([as, energy, traps, and, fluorescence, quenchers])]). relacion([sujeto(['To', this, 'end,', polymers, can]), verbo([act]), complemento([as, carriers, of, carbohydrates, in, 'so-called', 'glycopolymers,', which, mimic, the, multivalent, carbohydrate, functionalities])]). relacion([sujeto(['Finally,', these, polymers, were, tested, for, their, biological, availability, by, studying, their, lectin]), verbo([binding]), complemento([ability, with, 'Concanavalin', 'A'])]). relacion([sujeto(['This', document]), verbo([provides]), complemento([the, final, text, of, regulations, governing, employee, protection, '(', retaliation, or, 'whistleblower)', claims, under, section, 1558, of, the, 'Affordable', 'Care', 'Act,', which, added, section, 18, 'C', to, the, 'Fair', 'Labor', 'Standards', 'Act', to, provide, protections, to, employees, who, may, have, been, subject, to, retaliation, for, seeking, assistance, under, certain, affordability, assistance, provisions, '(', for, 'example,', health, insurance, premium, tax, 'credits)', or, for, reporting, potential, violations, of, the, 'Affordable', 'Care', 'Act\'s', consumer, protections, '(', for, 'example,', the, prohibition, on, 'rescissions)'])]). relacion([sujeto(['This', rule]), verbo([responds]), complemento([to, those, comments, and, establishes, the, final, procedures, and, time, frames, for, the, handling, of, retaliation, complaints, under, section, 18, 'C,', including, procedures, and, time, frames, for, employee, complaints, to, the, 'Occupational', 'Safety', and, 'Health', 'Administration', '(', 'OSHA),', investigations, by, 'OSHA,', appeals, of, 'OSHA', determinations, to, an, administrative, law, judge, '(', 'ALJ)', for, a, hearing, de, 'novo,', hearings, by, 'ALJs,', review, of, 'ALJ', decisions, by, the, 'Administrative', 'Review', 'Board', '(', 'ARB)', '(', acting, on, behalf, of, the, 'Secretary', of, 'Labor),', and, judicial, review, of, the, 'Secretary', of, 'Labor\'s', '(', 'Secretary\'s)', final, decision])]). relacion([sujeto(['We', outline, a, nine, step, framework, for, the, development, and, validation, of, 'taxon-specific', primers, for, eDNA, analysis, in, ecological, 'studies,']), verbo([involving]), complemento([reference, database, 'construction,', phylogenetic, evaluation, of, the, target, 'gene,', primer, 'design,', primer, evaluation, in, 'silico,', and, laboratory, evaluation, of, primer, 'specificity,', sensitivity, and, utility])]). relacion([sujeto(['The', first, five, steps, can, be, conducted, relatively, rapidly, and, '(', where, reference, 'DNA', sequences, are, 'available)']), verbo([require]), complemento([minimal, laboratory, 'resources,', enabling, assessment, of, primer, suitability, before, investing, in, further, work])]). relacion([sujeto(['Steps', six, to, eight]), verbo([require]), complemento([more, costly, laboratory, analyses, but, are, essential, to, evaluate, risks, of, 'false-positive', and, 'false-negative', 'results,', while, step, 9, relates, to, field, implementation])]). relacion([sujeto(['As', an, 'example,', we]), verbo([have]), complemento([developed, and, evaluated, primers, to, specifically, amplify, part, of, the, mitochondrial, 'ND2', gene, from, 'Australian', bandicoots])]). relacion([sujeto(['If', adopted, during, the, early, stages, of]), verbo([primer]), complemento(['development,', our, framework, will, facilitate, 'large-scale', implementation, of, 'well-designed', 'DNA', tests, to, detect, specific, wildlife, from, eDNA, samples])]). relacion([sujeto(['This', will]), verbo([provide]), complemento([researchers, and, managers, with, an, understanding, of, the, strengths, and, limitations, of, their, data, and, the, conclusions, that, can, be, drawn, from, them])]). relacion([sujeto(['Laser', trapping, and, manipulation, of, blood, cells, without, mechanical, contact]), verbo([have]), complemento([become, feasible, with, implication, of, laser, tweezers])]). relacion([sujeto(['The', operation, principle, of, laser, tweezers, is, based, on, the, property, of, strongly, focused, laser, beam, to]), verbo([act]), complemento([on, a, dielectric, microparticle, located, in, the, vicinity, of, the, beam, waist, with, a, force, that, drives, the, particle, to, the, equilibrium, location, and, holds, it, there])]). relacion([sujeto(['Hemoglobinopathies,', particularly, 'β-thalassemia', and, sickle, cell, 'disease,', are, characterized, by, great, phenotypic, variability, in, terms, of, disease, 'severity,', while, notable, differences]), verbo([have]), complemento([been, observed, in, hydroxyurea, treatment, efficacy])]). relacion([sujeto(['We']), verbo([have]), complemento([previously, shown, that, several, protein, factors, act, as, modifiers, of, fetal, hemoglobin, 'production,', exerting, their, effect, via, different, pathways])]). relacion([sujeto(['Here,', we, explored, whether, 'SIN3A', could]), verbo([act]), complemento([as, a, modifier, of, fetal, globin, gene, 'expression,', as, it, interacts, with, 'KLF10,', a, known, modifier, of, fetal, hemoglobin, production])]). relacion([sujeto(['We', show, that, 'SIN3A', genomic, variants, are]), verbo([associated]), complemento([both, with, 'β-thalassemia', disease, severity, '(', 'rs11072544)', as, well, as, hydroxyurea, treatment, response, '(', 'rs7166737)', in, 'β-hemoglobinopathies', patients])]). relacion([sujeto(['Our', findings, further, underline, that, fetal, hemoglobin, production, is, the, result, of, a, complex, interplay, in, which, several, human, globin, gene, cluster, variants]), verbo([interact]), complemento([with, protein, factors, encoded, by, modifier, genes, to, produce, the, observed, clinical, outcome])]). relacion([sujeto(['NAD', is, a, pyridine, nucleotide, that, is]), verbo([involved]), complemento([in, cell, metabolism, and, signaling, of, plant, growth, and, stress])]). relacion([sujeto(['Recently,', we]), verbo([reported]), complemento([on, the, multifaceted, nature, of, 'NAD-inducible', immunity, in, 'Arabidopsis'])]). relacion([sujeto(['Altogether,', 'NAD-induced', immune, effects]), verbo([confer]), complemento([resistance, to, diverse, pathogenic, microbes])]). relacion([sujeto(['Managing', invasive, alien, species, in, 'Canada']), verbo([requires]), complemento([reliable, taxonomic, identification, as, the, basis, of, 'rapid-response', management])]). relacion([sujeto(['Canadian', policy, and, law, must, also, be, harmonized, with, that, of, the, 'USA', when, 'detecting,', and]), verbo([responding]), complemento(['to,', invasive, species, in, contiguous, lands, and, waters])]). relacion([sujeto(['Molecular', characterization, of, neuron, 'populations,', particularly, those, controlling, threat, 'responses,', is, essential, for, understanding, the, cellular, basis, of, behaviour, and, identifying, pharmacological, agents]), verbo([acting]), complemento([selectively, on, 'fear-controlling', circuitry])]). relacion([sujeto(['Thy1-eNpHR-,', 'Thy1-Cre-', and, 'Thy1-eYFP-labelled', neurons, of, the, 'BLA', consistently]), verbo([act]), complemento([as, fear, inhibiting, or, '\'', 'Fear-Off\'', neurons, during, behaviour])]). relacion([sujeto(['We', use, 'cell-type-specific', optogenetics, and, chemogenetics, '(', 'DREADDs)', to]), verbo([modulate]), complemento([activity, in, this, population, during, behaviour, to, block, or, enhance, fear, extinction])]). relacion([sujeto(['RCC', is, lethal, at, metastatic, stage, as, it, does, not]), verbo([respond]), complemento([to, conventional, systemic, 'treatments,', and, there, is, an, urgent, need, to, find, out, promising, novel, biomarkers, for, effective, treatment])]). relacion([sujeto(['The', goal, of, this, study, was, to, evaluate, the, biomarkers, that, can, be, potential, therapeutic]), verbo([target]), complemento([and, predict, effective, inhibitors, to, treat, the, metastatic, stage, of, 'RCC'])]). relacion([sujeto(['We', conducted, transcriptomic, profiling, to, identify, differentially]), verbo([expressed]), complemento([genes, associated, with, 'RCC'])]). relacion([sujeto(['Molecular', docking, analyses, were, performed, to, check, the, potential, of, two, natural, 'inhibitors,', rutin, and, curcumin, to]), verbo([bind]), complemento(['CCND1'])]). relacion([sujeto(['We', detected, 1490, significantly]), verbo([expressed]), complemento([genes, '(', 1034, ',', upregulated, and, 456, ',', 'downregulated)', in, 'RCC', using, cutoff, fold, change, 2, and, p, value, &, 'lt;', 0.05])]). relacion([sujeto(['Hes-related', family, bHLH, transcription, factor, with, 'YRPW', motif, 1, '(', 'HEY1),', neuropilin, 2, '(', 'NRP2),', lymphoid, 'enhancer-binding', factor, 1, '(', 'LEF1),', and, histone, cluster, 1, 'H3h', '(', 'HIST1H3H)', were, most, upregulated, while, aldolase, 'B,', 'fructose-bisphosphate', '(', 'ALDOB),', solute, carrier, family, 12, '(', 'SLC12A1),', calbindin, 1, '(', 'CALB1)', were, the, most, down]), verbo([regulated]), complemento([genes, in, our, dataset])]). relacion([sujeto(['Functional', analysis, revealed, 'Wnt/β-catenin', signaling, as, the, significantly]), verbo([activated]), complemento([canonical, pathway, '(', z, score, =, 2.53, ')', involving, cyclin, 'D1', '(', 'CCND1)'])]). relacion([sujeto(['Docking', study, showed, that, 'CCND1', may]), verbo([act]), complemento([as, a, potential, therapeutic, target, and, its, inhibition, could, focus, on, the, 'migratory,', 'invasive,', and, metastatic, potential, of, 'RCC'])]). relacion([sujeto(['Further', in, vivo, and, in, vitro, molecular, studies, are, needed, to, investigate, the, therapeutic]), verbo([target]), complemento([potential, of, 'CCND1', for, 'RCC', treatment])]). relacion([sujeto(['Purple', acid, phosphatases, '(', 'PAPs)', are, binuclear, 'metallo-hydrolases', that]), verbo([have]), complemento([been, isolated, from, various, 'mammals,', 'plants,', fungi, and, bacteria])]). relacion([sujeto(['In', 'mammals,', 'PAP', activity, is]), verbo([associated]), complemento([with, bone, resorption, and, can, lead, to, bone, metabolic, disorders, such, as, 'osteoporosis;', thus, human, 'PAP', is, an, attractive, target, to, develop, 'anti-osteoporotic', drugs])]). relacion([sujeto(['Enzyme', kinetic, data, showed, that, they, are, good, rkbPAP, inhibitors, whose, potencies, improve, with]), verbo([increasing]), complemento([alkyl, chain, length])]). relacion([sujeto(['Hexadecyl', 'derivatives,', as, most, potent, compounds, '(', 'Ki', =, 1.1, 'µM),']), verbo([inhibit]), complemento([rkbPAP, in, the, mixed, 'manner,', while, dodecyl, derivatives, act, as, efficient, noncompetitive, inhibitor])]). relacion([sujeto(['Also,', analysis, by, molecular, modeling, of, the, structure, of, the, 'rkbPAP-inhibitor', complexes]), verbo([reveals]), complemento(['factors,', which, may, be, important, for, the, determination, of, inhibition, specificity])]). relacion([sujeto(['The', 'Schiff', bases]), verbo([act]), complemento([as, tridentate, ligands, toward, metal, ions, via, 'azomethine-N,', 'deprotonated-N', of, ammine, substituents, and, 'S-atom', of, thienyl, moiety])]). relacion([sujeto(['The', results, of, antimicrobial, studies, revealed, the, free, ligands, to, possess, potential, activity, which, significantly]), verbo([increased]), complemento([upon, chelation])]). relacion([sujeto(['The', 'Klotho', is, known, as, lifespan]), verbo([enhancing]), complemento([protein, involved, in, antagonizing, the, effect, of, 'Wnt', proteins])]). relacion([sujeto(['Wnt', proteins, are, stem, cell, 'regulators,', and, uninterrupted, exposure, of, 'Wnt', proteins, to, the, cell, can]), verbo([cause]), complemento([stem, and, progenitor, cell, 'senescence,', which, may, lead, to, aging])]). relacion([sujeto(['Keeping', in, mind, the, importance, of, 'Klotho', in, 'Wnt', 'signaling,', in, silico, approaches]), verbo([have]), complemento([been, applied, to, study, the, important, interactions, between, 'Klotho', and, 'Wnt3', and, 'Wnt3a', '(', 'wingless-type', mouse, mammary, tumor, virus, '(', 'MMTV)', integration, site, family, members, 3, and, 3, 'a)'])]). relacion([sujeto(['The', main, aim, of, the, study, is, to, identify, important, residues, of, the, 'Klotho', that, help, in, designing, peptides, which, can]), verbo([act]), complemento([as, 'Wnt', antagonists])]). relacion([sujeto(['During', the, theoretical, analysis, of, homology, 'models,', unexpected, role, of, number, of, disulfide, bonds, and, secondary, structure, elements]), verbo([has]), complemento([been, witnessed, in, case, of, 'Wnt3', and, 'Wnt3a', proteins])]). relacion([sujeto(['Based', on, the, 'protein-protein', docking, simulations, of, selected, protein, models, of, 'Klotho', with, 'Wnt3', and, 'Wnt3a,', different, peptides, derived, from, 'Klotho']), verbo([have]), complemento([been, designed])]). relacion([sujeto(['Wnt3', and, 'Wnt3a', proteins]), verbo([have]), complemento([three, important, 'domains:', 'Index', 'finger,', 'N-terminal', domain, and, a, patch, of, '∼10', residues, on, the, solvent, exposed, surface, of, palm, domain])]). relacion([sujeto(['Protein-peptide', docking, of, designed, peptides, of, 'Klotho', against, three, important, domains, of, palmitoylated, 'Wnt3', and, 'Wnt3a', yields, encouraging, results, and]), verbo([leads]), complemento([better, understanding, of, the, 'Wnt', protein, inhibition, by, proposed, 'Klotho', peptides])]). relacion([sujeto(['Structural', studies, of, the, major, glycolipids, produced, by, two, 'Lactobacillus', johnsonii, '(', 'LJ)', 'strains,', 'LJ', 151, isolated, from, intestinal, tract, of, healthy, mice, and, 'LJ', 142, isolated, from, mice, with, experimentally]), verbo([induced]), complemento([inflammatory, bowel, disease, '(', 'IBD),', were, performed])]). relacion([sujeto(['Glycolipid', 'GL1']), verbo([has]), complemento([been, identified, as, 'β-D-Glcp-(1→6)-α-D-Galp-(1→2)-α-D-Glcp-diglyceride', and, 'GL2', as, 'α-D-Galp-(1→2)-α-D-Glcp-diglyceride'])]). relacion([sujeto(['Results', indicate, that, glycoconjugates, from, 'Lactobacillus', cell, wall]), verbo([act]), complemento([as, antigens, and, may, represent, new, 'IBD', diagnostic, biomarkers])]). relacion([sujeto(['Cholera', routine, vaccination]), verbo([has]), complemento([failed, in, controlling, epidemics, in, developing, countries, because, of, their, hard, and, expensive, production])]). relacion([sujeto(['Although', 'LPS', of, 'Vibrio,', as, an, 'endotoxin,', can]), verbo([stimulate]), complemento([the, immune, 'system,', thereby, making, it, a, suitable, candidate, for, cholera, 'vaccine,', its, toxicity, remains, as, a, main, problem])]). relacion([sujeto(['The', screening, was, carried, out, using, 'single-domain', antibody, fragment, 'VHH', against, 'LPS', as]), verbo([target]), complemento([through, three, rounds, of, selection])]). relacion([sujeto(['To']), verbo([find]), complemento([out, a, new, and, efficient, vaccine, against, 'cholera,', these, three, phage, particles, containing, 'high-affinity', peptides, were, administered, to, mice, to, investigate, the, active, and, passive, immunity])]). relacion([sujeto(['These', three, selected, phages, '(', individually, or, in, 'combination)', could]), verbo([stimulate]), complemento([mice, immune, system, producing, active, and, passive, immunity])]). relacion([sujeto(['In', 'conclusion,', these, peptides, are, mimicking, 'LPS', and, can, potentially]), verbo([act]), complemento([as, vaccine, candidates, against, 'V'])]). relacion([sujeto(['Utilization', of, social, media, both, in, the, private, and, professional, arenas]), verbo([has]), complemento([grown, rapidly, in, the, last, decade])]). relacion([sujeto(['For', orthopedic, surgeons, and, their, 'practices,', 'general-purpose', online, social, 'networks,', such, as, 'Facebook', and, 'Twitter,', are, convenient, platforms, for, 'marketing,']), verbo([providing]), complemento([patient, education, and, generating, referrals])]). relacion([sujeto(['Virtual', health, communities, are, used, less, frequently, by, orthopedic, surgeons, but]), verbo([provide]), complemento([forums, for, patient, engagement, and, active, 'surgeon-to-patient', communication, via, blogs, and, 'ask-the-doctor', platforms])]). relacion([sujeto(['In', the, last, 20, years, it]), verbo([has]), complemento([been, widely, demonstrated, that, cell, nucleus, contains, neutral, and, polar, lipids, localized, in, nuclear, 'membranes,', 'nucleoli,', nuclear, matrix, and, chromatin])]). relacion([sujeto(['Nuclear', lipids, may, show, specific, organization, forming]), verbo([nuclear]), complemento([lipid, microdomains, and, have, both, structural, and, functional, roles])]). relacion([sujeto(['Depending', on, their, 'localization,']), verbo([nuclear]), complemento([lipids, play, different, roles, such, as, the, regulation, of, nuclear, membrane, and, nuclear, matrix, fluidity, but, they, also, can, act, as, platforms, for, vitamin, and, hormone, 'function,', for, active, chromatin, 'anchoring,', and, for, the, regulation, of, gene, 'expression,', 'DNA', duplication, and, transcription])]). relacion([sujeto(['In', neural, cells, the]), verbo([nuclear]), complemento([lipids, are, involved, in, cell, 'proliferation,', 'differentiation,', 'inflammation,', migration, and, apoptosis])]). relacion([sujeto(['Abnormal', metabolism, of]), verbo([nuclear]), complemento([lipids, might, be, closely, associated, with, tumorigenesis, and, neurodegenerative, diseases, such, as, 'Alzheimer', disease, and, 'Parkinson', disease, among, others])]). relacion([sujeto(['This', manuscript]), verbo([reports]), complemento([the, identification, and, characterization, of, five, transcription, factors, binding, to, the, promoter, of, 'OsNHX1', in, a, salt, stress, tolerant, rice, genotype, '(', 'Hasawi)'])]). relacion([sujeto(['Although', 'NHX1', encoding, genes, are, known, to, be, highly]), verbo([regulated]), complemento([at, the, transcription, level, by, different, abiotic, 'stresses,', namely, salt, and, drought, 'stress,', until, now, only, 'one transcription', factor, '(', 'TF)', binding, to, its, promoter, has, been, reported])]). relacion([sujeto(['In', order, to, unveil, the, 'TFs']), verbo([regulating]), complemento(['NHX1', gene, 'expression,', which, is, known, to, be, highly, induced, under, salt, 'stress,', we, have, used, a, 'Y1H', system, to, screen, a, salt, induced, rice, cDNA, expression, library, from, 'Hasawi'])]). relacion([sujeto(['This', approach, allowed, us, to, identify, five, 'TFs', belonging, to, three, distinct, 'TF', 'families:', one, 'TCP', '(', 'OsPCF2),', one, 'CPP', '(', 'OsCPP5)', and, three, 'NIN-like', '(', 'OsNIN-like2,', 'OsNIN-like3', and, 'OsNIN-like4)']), verbo([binding]), complemento([to, the, 'OsNHX1', gene, promoter])]). relacion([sujeto(['We']), verbo([have]), complemento([also, shown, that, these, 'TFs', act, either, as, transcriptional, activators, '(', 'OsPCF2,', 'OsNIN-like4)', or, repressors, '(', 'OsCPP5,', 'OsNIN-like2)', and, their, encoding, genes, are, differentially, regulated, by, salt, and, 'PEG-induced', drought, stress, in, two, rice, 'genotypes,', 'Nipponbare', '(', 'salt-sensitive)', and, 'Hasawi', '(', 'salt-tolerant)'])]). relacion([sujeto(['Increased', soil, salinity]), verbo([has]), complemento([a, direct, impact, on, the, reduction, of, plant, growth, and, crop, yield, and, it, is, therefore, fundamental, to, understand, the, molecular, mechanisms, underlying, gene, expression, regulation, under, adverse, environmental, conditions])]). relacion([sujeto(['OsNHX1', is, the, most, abundant, 'K(+)-Na(+)/H(+)', antiporter, localized, in, the, tonoplast, and, its, gene, expression, is]), verbo([induced]), complemento([by, 'salt,', drought, and, 'ABA'])]). relacion([sujeto(['To', investigate, how, 'OsNHX1', is, transcriptionally]), verbo([regulated]), complemento([in, response, to, salt, stress, in, a, 'salt-tolerant', rice, genotype, '(', 'Hasawi),', a, 'salt-stress-induced', cDNA, expression, library, was, constructed, and, subsequently, screened, using, the, yeast, 'one-hybrid', system, and, the, 'OsNHX1', promoter, as, bait])]). relacion([sujeto(['Five', transcription, factors, '(', 'TFs)', belonging, to, three, distinct, 'TF', 'families:', one, 'TCP', '(', 'OsPCF2),', one, 'CPP', '(', 'OsCPP5)', and, three, 'NIN-like', '(', 'OsNIN-like2,', 'OsNIN-like3', and, 'OsNIN-like4)', were, identified, as]), verbo([binding]), complemento([to, 'OsNHX1', promoter])]). relacion([sujeto(['Transactivation', activity, assays, performed, in, 'Arabidopsis', and, rice, protoplasts, showed, that, 'OsPCF2', and, 'OsNIN-like4', are, activators, of, the, 'OsNHX1', gene, 'expression,', while, 'OsCPP5', and, 'OsNIN-like2']), verbo([act]), complemento([as, repressors])]). relacion([sujeto(['Gene', expression, studies, showed, that, 'OsNHX1', transcript, level, is, highly]), verbo([induced]), complemento([by, salt, and, 'PEG-induced', drought, stress, in, both, shoots, and, roots, in, both, 'Nipponbare', and, 'Hasawi', rice, genotypes])]). relacion([sujeto(['Most', of, the, 'TFs']), verbo([binding]), complemento([to, 'OsNHX1', promoter, showed, a, modest, transcriptional, regulation, under, stress, 'conditions,', 'however,', in, response, to, most, of, the, conditions, 'studied,', the, 'OsPCF2', was, induced, earlier, than, 'OsNHX1,', indicating, that, 'OsPCF2', may, activate, 'OsNHX1', gene, expression])]). relacion([sujeto(['In', 'addition,', although, the, 'OsNHX1', response, to, salt, and, 'PEG-induced', drought, stress, in, either, shoots, or, roots, was, quite, similar, in, both, rice, 'genotypes,', the, expression, of, 'OsPCF2', in, roots, under, salt, stress, and, the, 'OsNIN-like4', in, roots, subjected, to, 'PEG', was, mainly, 'up-regulated', in, 'Hasawi,', indicating, that, these, 'TFs', may, be]), verbo([associated]), complemento([with, the, salt, and, drought, stress, tolerance, observed, for, this, genotype])]). relacion([sujeto(['The', public, health, risks]), verbo([associated]), complemento([with, dairy, farming, intensification, are, an, emerging, concern])]). relacion([sujeto(['Multi-level', 'Poisson', regression, was, used, to, model]), verbo([reported]), complemento([cryptosporidiosis, '(', 'N = 3869', 'cases)', incidence, in, relation, to, dairy, cattle, densities, across, urban, and, rural, areas, 'separately,', after, controlling, for, microbiological, quality, of, public, drinking, water, supplies, and, neighbourhood, 'socio-economic', factors, using, the, 'Census', 'Area', 'Unit', of, residence])]). relacion([sujeto(['Within', urban, 'areas,', the, risk, of, cryptosporidiosis, in, children, less, than, 5, &, 'nbsp;years', old, was, 'significantly,', positively]), verbo([associated]), complemento([with, medium, and, high, dairy, cattle, density, 'IRR', 1.3, '(', 95, '%', 'CI', 1.2, ',', 1.5, ')', and, 1.5, '(', 95, '%', 'CI', 1.2, ',', 1.9, ')', 'respectively,', when, compared, to, areas, with, no, dairy, cattle])]). relacion([sujeto(['Within', rural, 'areas,', the, incidence, risk, of, cryptosporidiosis, in, children, less, than, 5, &, 'nbsp;years', old, were, 'significantly,', positively]), verbo([associated]), complemento([with, medium, and, high, dairy, cattle, 'density:', 'IRR', 1.7, '(', 95, '%', 'CI', 1.3, ',', 2.3, ')', and, 2.0, '(', 95, '%', 'CI', 1.5, ',', 2.8, ')', 'respectively,', when, compared, to, areas, with, no, dairy, cattle])]). relacion([sujeto(['These', results]), verbo([have]), complemento([public, health, implications, for, children, living, on, and, in, proximity, to, intensively, stocked, dairy, cattle, farms])]). relacion([sujeto(['Obesity-related', insulin, resistance, is]), verbo([associated]), complemento([with, fatty, 'liver,', 'dyslipidemia,', and, low, plasma, adiponectin])]). relacion([sujeto(['Insulin', resistance, due, to, insulin, receptor, '(', 'INSR)', dysfunction, is]), verbo([associated]), complemento([with, none, of, 'these,', but, when, due, to, dysfunction, of, the, downstream, kinase, 'AKT2', phenocopies, 'obesity-related', insulin, resistance])]). relacion([sujeto(['We']), verbo([report]), complemento([5, patients, with, 'SHORT', syndrome, and, 'C-terminal', mutations, in, 'PIK3R1,', encoding, the, 'p85α/p55α/p50α', subunits, of, 'PI3K,', which, act, between, 'INSR', and, 'AKT', in, insulin, signaling])]). relacion([sujeto(['The', fourth, patient, and, her, healthy, mother, had, low, plasma, adiponectin]), verbo([associated]), complemento([with, a, potentially, novel, 'mutation,', p])]). relacion([sujeto(['Tyr657X', 'PIK3R1', mutation]), verbo([expressed]), complemento([abundant, truncated, 'PIK3R1', products, and, showed, severely, reduced, 'insulin-stimulated', association, of, mutant, but, not, 'WT', p85α, with, 'IRS1,', but, normal, downstream, signaling])]). relacion([sujeto(['Furthermore,', the, in, situ, formed, nonfluorescent, 'Cu(2+)-DHC', complex, can]), verbo([act]), complemento([as, an, effective, 'off-on', type, fluorescent, probe, for, sensing, 'PPi', due, to, the, higher, coordination, reactivity, between, 'Cu(2+)', and, 'PPi', than, that, between, 'Cu(2+)', and, 'DHC'])]). relacion([sujeto(['The', subsequent, addition, of, 'PPase', to, the, mixture, containing, 'Cu(2+),', 'DHC,', and, 'PPi']), verbo([leads]), complemento([to, the, fluorescence, requenching, of, the, system, again, '(', an, off, 'state)', because, 'PPase', catalyzes, the, hydrolysis, of, 'PPi', into, orthophosphate, in, the, reaction, system])]). relacion([sujeto(['Under', the, optimum, 'conditions,', the]), verbo([decrease]), complemento([of, the, fluorescence, intensity, of, 'DHC-Cu(2+)-PPi', system, was, linear, with, the, increase, of, the, 'PPase', activity, in, the, range, from, 0.1, to, 0.3, 'U'])]). relacion([sujeto(['While', limited, scientific, evidence, exists, to, substantiate, these, 'claims,', previous, studies]), verbo([have]), complemento([shown, that, high, levels, of, 'fitness,', strength, and, balance, exists, amongst, participants, of, this, sport])]). relacion([sujeto(['An', intervention, study, was, conducted, where, after, being, tested, 'initially,', subjects, were, left, for, 6, &, 'nbsp;weeks', to]), verbo([act]), complemento([as, their, own, control, before, the, 'SUP', intervention, began])]). relacion([sujeto(['The', result, from, this, study]), verbo([provides]), complemento([some, evidence, to, substantiate, the, claims, of, health, and, fitness, benefits, 'SUP'])]). relacion([sujeto(['In', addition, to, its, microbicidal, 'activity,', 'WLE', may]), verbo([act]), complemento([as, an, antioxidant, as, it, exerted, radical, scavenging, activity, against, 2, ',', 2, -, 'diphenyl-1-picrylhydrazyl,', a, stable, free, radical])]). relacion([sujeto(['Although', comprehensive, studies]), verbo([have]), complemento([been, done, to, investigate, responses, of, various, ecosystem, processes, to, rising, air, 'temperatures,', less, is, known, about, changes, in, soil, temperatures, and, their, impact, on, 'below-ground', 'processes,', particularly, in, deep, layers])]). relacion([sujeto(['We', 'determined,', apparently, for, the, first, 'time,', that, soil, surface, temperature]), verbo([increased]), complemento([31, '%', more, than, air, 'temperature,', potentially, leading, to, more, carbon, release, to, the, atmosphere, than, predicted])]). relacion([sujeto(['Annual', mean, surface, temperature]), verbo([increased]), complemento([by, 2.07, -, 4.04, and, 0.66, -, 2.21, °, 'C', in, northern, and, southern, 'China,', 'respectively,', with, the, greatest, in, winter])]). relacion([sujeto(['The', soil, temperature, rise, was, predicted, to]), verbo([have]), complemento([increased, soil, respiration, by, up, to, 28, '%', ',', reinforcing, climate, warming, and, extending, the, potential, growing, season, by, up, to, 20, d, across, 'China'])]). relacion([sujeto(['The', mammalian, 'Hedgehog', '(', 'Hh)', signaling, pathway, is]), verbo([required]), complemento([for, development, and, for, maintenance, of, adult, stem, 'cells,', and, overactivation, of, the, pathway, can, cause, tumorigenesis])]). relacion([sujeto(['All', responses, to, 'Hh', family, ligands, in, mammals]), verbo([require]), complemento([the, primary, 'cilium,', an, ancient, 'microtubule-based', organelle, that, extends, from, the, cell, surface])]). relacion([sujeto(['Genetic', studies, in, mice, and, humans]), verbo([have]), complemento([defined, specific, functions, for, 'cilium-associated', microtubule, motor, 'proteins:', they, act, in, the, construction, and, disassembly, of, the, primary, 'cilium,', they, control, ciliary, length, and, 'stability,', and, some, have, direct, roles, in, mammalian, 'Hh', signal, transduction])]). relacion([sujeto(['High', performance, liquid, chromatography, '(', 'HPLC)', is, a, kind, of, efficient, separation, technology, and]), verbo([has]), complemento([been, used, widely, in, many, fields])]). relacion([sujeto(['Micro-sized', porous, silica, microspheres, as, the, most, popular, matrix]), verbo([have]), complemento([been, used, for, fast, separation, and, analysis, in, 'HPLC'])]). relacion([sujeto(['First,', the, 'poly(glycidyl', 'methacrylate-co-ethyleneglycol', 'dimethacrylate)', microspheres, '(', 'PGMA-EDMA)', were, functionalized, with, tetraethylenepentamine, '(', 'TEPA)', to, generate, amino, groups, which]), verbo([act]), complemento([as, a, catalyst, in, hydrolysis, of, tetraethyl, orthosilicate, '(', 'TEOS)', to, form, 'Si-containing', low, molecular, weight, species])]). relacion([sujeto(['Many', 'plant-derived', chemicals]), verbo([have]), complemento([been, studied, for, their, potential, benefits, in, ailments, including, 'inflammation,', 'cancer,', 'neurodegeneration,', and, cardiovascular, disease])]). relacion([sujeto(['The', health, benefits, of, phytochemicals, are, often, attributed, to, the]), verbo([targeting]), complemento([of, reactive, oxygen, species, '(', 'ROS)'])]). relacion([sujeto(['However,', it, is, not, always, clear, whether, these, agents]), verbo([act]), complemento([directly, as, antioxidants, to, remove, 'ROS,', or, whether, they, act, indirectly, by, blocking, 'ROS', production, by, enzymes, such, as, 'NADPH', oxidase, '(', 'NOX)', 'enzymes,', or, by, influencing, the, expression, of, cellular, 'pro-', and, 'anti-', oxidants])]). relacion([sujeto(['This', work, was, done, using, the, 'H661', cell, line]), verbo([expressing]), complemento([little, or, no, 'NOX,', modified, 'H661', cells, expressing, 'NOX1', and, its, 'subunits,', and, an, 'EBV-transformed', 'B-lymphoblastoid', cell, line, expressing, endogenous, 'NOX2'])]). relacion([sujeto(['The', results, of, this, study]), verbo([reveal]), complemento([the, differences, that, exist, between, 'cell-free', and, intracellular, 'pro-oxidant', and, antioxidant, activities, of, several, 'plant-derived', compounds])]). relacion([sujeto(['The', genus, 'Xylaria']), verbo([has]), complemento([been, reported, as, a, rich, source, of, biologically, active, secondary, metabolites])]). relacion([sujeto(['In', the, present, 'study,', an, endophytic, fungus, 'Xylaria', psidii]), verbo([has]), complemento([been, isolated, from, the, leaf, sample, of, 'Aegle', marmelos, '(', 'L'])]). relacion([sujeto([',', characterized, on, the, basis, of, its, morphological, features, and, sequence, data, for, the, 'ITS', region, '(', 'KU291350)', of, the]), verbo([nuclear]), complemento([ribosomal, 'DNA'])]). relacion([sujeto(['The', structures, of, 1, and, 2]), verbo([have]), complemento([been, determined, by, detailed, spectroscopic, analysis, including, 'MS,', 'NMR,', 'IR', and, 'UV', data, and, similarity, with, published, data])]). relacion([sujeto(['Xylarione', 'A', '(', 1, ')', is, new, whereas, '(', -, ')', 5, -, methylmellein, '(', 2, ')', is]), verbo([reported]), complemento([for, the, first, time, from, 'X'])]). relacion([sujeto(['The', cell, cycle, distribution, in, 'MIA-Pa-Ca-2', 'cells,', confirmed, a, cell, cycle]), verbo([arrest]), complemento([at, the, 'sub-G1', phase])]). relacion([sujeto(['Cell', death]), verbo([induced]), complemento([by, 1, and, 2, displayed, features, characteristic, of, apoptosis])]). relacion([sujeto(['Flow', cytometry, based, analysis, of, 1, and, 2, using, 'Rhodamine-123', displayed, substantial]), verbo([loss]), complemento([of, mitochondrial, membrane, potential, in, a, concentration, dependent, manner, by, both, the, compounds])]). relacion([sujeto(['Results', conclude, that, the, isolated, compounds, 1, and, 2, are, responsible, for, the, activity, shown, by, crude, ethyl, acetate, extract, and, may]), verbo([act]), complemento([as, potential, leads, for, medicinal, chemists, for, designing, more, potent, analogs])]). relacion([sujeto(['Circadian', controls]), verbo([act]), complemento([as, a, '\'', 'memory\'', of, the, past, conditions, experienced, by, the, 'plant,', which, synchronizes, metabolism, across, entire, plant, canopies])]). relacion([sujeto(['There', are, several, instruments, of, 'PSE', for]), verbo([promoting]), complemento([healthy, dietary, or, physical, activity, '(', 'PA)', behaviors, in, children])]). relacion([sujeto(['Swedish', mothers, of, 'five-year-old', children, '(', n, =, 698, ')']), verbo([responded]), complemento([to, the, 'Parental', 'Self-Efficacy', for, 'Healthy', 'Dietary', and, 'Physical', 'Activity', 'Behaviors', in, 'Preschoolers', 'Scale', '(', 'PDAP)', and, a, questionnaire, on, dietary, and, 'PA', behaviors, in, children])]). relacion([sujeto(['A', 'four-factor', model, of, a, revised, 21, -, item, version, of, the, 'PDAP', fitted, the, 'data,', with, different, factors, of, 'PSE', for]), verbo([promoting]), complemento([healthy, dietary, or, 'PA', behaviors, in, children, depending, on, whether, circumstances, were, facilitating, or, impeding, successful, performance])]). relacion([sujeto(['Psychometric', evaluation, of, the, 'PDAP']), verbo([provided]), complemento([preliminary, support, of, construct, validity, and, internal, consistency])]). relacion([sujeto(['The', interviews, were]), verbo([transcribed]), complemento([verbatim, and, analyzed, according, to, the, constant, comparative, method])]). relacion([sujeto(['Besides']), verbo([providing]), complemento([linguistic, 'translation,', informal, interpreters, were, expected, to, perform, the, roles, of, advocates, and, caregivers, of, the, patients])]). relacion([sujeto(['Informal', interpreters, were, trusted, more, than, professional, 'interpreters,', mainly, for, fidelity, 'reasons,', that, 'is,', because, the, patients, assumed, that, informal, interpreters, would]), verbo([act]), complemento([in, their, best, interests])]). relacion([sujeto(['Immune', thrombocytopenia, purpura, '(', 'ITP)', is, characterized, by, the, production, of, pathological, autoantibodies, that]), verbo([cause]), complemento([reduction, in, platelet, counts])]). relacion([sujeto(['The', disease, can]), verbo([have]), complemento([serious, medical, 'consequences,', leading, to, uncontrolled, bleeding, that, can, be, fatal])]). relacion([sujeto(['The', 'nanoparticles,', whose, outer, layer, displays, the, full, complement, of, native, platelet, surface, 'proteins,']), verbo([act]), complemento([as, decoys, that, strongly, bind, pathological, 'anti-platelet', antibodies, in, order, to, minimize, disease, burden])]). relacion([sujeto(['Here,', we, study, the, antibody]), verbo([binding]), complemento([properties, of, 'PNPs', and, assess, the, ability, of, the, nanoparticles, to, neutralize, antibody, activity, both, 'in vitro', and, 'in vivo'])]). relacion([sujeto(['PNPs', represent, a, promising, platform, for, the, specific, treatment, of, 'antibody-mediated', immune, thrombocytopenia, by]), verbo([acting]), complemento([as, an, alternative, target, for, 'anti-platelet', 'antibodies,', thus, preserving, circulating, platelets, with, the, potential, of, leaving, broader, immune, function, intact])]). relacion([sujeto(['Restricted', and, repetitive, behaviors, are, a, defining, feature, of, 'autism,', which, can, be]), verbo([expressed]), complemento([as, a, cognitive, flexibility, deficit, or, 'stereotyped,', motor, behaviors])]). relacion([sujeto(['Previous', findings]), verbo([suggest]), complemento([that, central, 5, 'HT2A', receptor, activity, is, altered, in, 'autism,', while, recent, work, indicates, that, systemic, 5, 'HT2A', receptor, antagonist, treatment, reduces, repetitive, behaviors, in, an, idiopathic, model, of, autism])]). relacion([sujeto([5, 'HT2A', receptors, are]), verbo([expressed]), complemento([in, the, orbitofrontal, cortex, and, striatum])]). relacion([sujeto(['These', two, regions]), verbo([have]), complemento([been, shown, to, be, altered, in, autism])]). relacion([sujeto(['M100907', infusion, into, the, orbitofrontal, cortex]), verbo([increased]), complemento([perseveration, during, reversal, learning, and, potentiated, grooming])]). relacion([sujeto(['These', findings]), verbo([suggest]), complemento([that, increased, 5, 'HT2A', receptor, activity, in, the, dorsomedial, striatum, may, contribute, to, behavioral, inflexibility, and, stereotyped, behaviors, in, the, 'BTBR', mouse])]). relacion([sujeto([5, 'HT2A', receptor, signaling, in, the, orbitofrontal, cortex, may, be, critical, for]), verbo([inhibiting]), complemento([a, previously, learned, response, during, reversal, learning, and, expression, of, stereotyped, behavior])]). relacion([sujeto(['The', present, results]), verbo([suggest]), complemento([which, brain, areas, exhibit, abnormalities, underlying, repetitive, behaviors, in, an, idiopathic, mouse, model, of, 'autism,', as, well, as, which, brain, areas, systemic, treatment, with, 'M100907', may, principally, act, on, in, 'BTBR', mice, to, attenuate, repetitive, behaviors])]). relacion([sujeto(['The', first, quaternary, 'ammonium-group-containing', '[', 'FeFe]-hydrogenase', models, '[', '(', 'μ-PDT)Fe2', '(', 'CO)4', '{', 'κ(2)', -, '(', 'Ph2', 'P)2', 'N(CH2', ')', 2, 'NMe2', 'BzBr}]', '(', 2, ;, 'PDT=propanedithiolate)', and, '[', '(', 'μ-PDT)Fe2', '(', 'CO)4', '{', 'μ-(Ph2', 'P)2', 'N(CH2', ')', 2, 'NMe2', 'BzBr}]', '(', 4, ')']), verbo([have]), complemento([been, prepared, by, the, quaternization, of, their, precursors, '[', '(', 'μ-PDT)Fe2', '(', 'CO)4', '{', 'κ(2)', -, '(', 'Ph2', 'P)2', 'N(CH2', ')', 2, 'NMe2', '}', ']', '(', 1, ')', and, '[', '(', 'μ-PDT)Fe2', '(', 'CO)4', '{', 'μ-(Ph2', 'P)2', 'N(CH2', ')', 2, 'NMe2', '}', ']', '(', 3, ')', with, benzyl, bromide, in, high, yields])]). relacion([sujeto(['Although', new, complexes, 1, -, 4]), verbo([have]), complemento([been, fully, characterized, by, spectroscopic, and, 'X-ray', crystallographic, 'studies,', the, chelated, complexes, 1, and, 2, converted, into, their, bridged, isomers, 3, and, 4, at, higher, 'temperatures,', thus, demonstrating, that, these, bridged, isomers, are, thermodynamically, favorable])]). relacion([sujeto(['In', 'addition,', hydrophilic, models, 2, and, 4]), verbo([act]), complemento([as, electrocatalysts, and, achieve, higher, icat, /, ip, values, and, turnover, numbers, '(', 'TONs)', in, 'MeCN/H2', 'O', as, a, solvent, than, in, 'MeCN', for, the, production, of, hydrogen, from, the, weak, acid, 'HOAc'])]). relacion([sujeto(['Depending', on, the, amount, of, methanol, present, in, 'solution,', 'CO2', adducts, of, 'N-heterocyclic', carbenes, '(', 'NHCs)', and, 'N-heterocyclic', olefins, '(', 'NHOs)']), verbo([have]), complemento([been, found, to, be, in, fully, reversible, equilibrium, with, the, corresponding, methyl, carbonate, salts, '[', 'EMIm][OCO2', 'Me]', and, '[', 'EMMIm][OCO2', 'Me]'])]). relacion([sujeto(['The', reactivity, pattern, of, representative, 1, -, 'ethyl-3-methyl-NHO-CO2', adduct, 4]), verbo([has]), complemento([been, investigated, and, compared, with, the, corresponding, 'NHC-CO2', 'zwitterion:', 'The', protonation, of, 4, with, 'HX', led, to, the, imidazolium, salts, '[', 'NHO-CO2', 'H][X],', which, underwent, decarboxylation, to, '[', 'EMMIm][X]', in, the, presence, of, nucleophilic, catalysts])]). relacion([sujeto(['NHO-CO2', zwitterion, 4, can]), verbo([act]), complemento([as, an, efficient, carboxylating, agent, towards, 'CH', acids, such, as, acetonitrile])]). relacion([sujeto(['The', reaction, of, the, free, 'NHO', with, dimethyl, carbonate, selectively]), verbo([led]), complemento([to, methoxycarbonylated, 'NHO,', which, is, a, perfect, precursor, for, the, synthesis, of, functionalized, 'ILs', '[', 'NHO-CO2', 'Me][X]'])]). relacion([sujeto(['Tuberculosis', '(', 'TB)', is, a, major, disease, burden, globally]), verbo([causing]), complemento([more, than, 1.5, million, deaths, per, year])]). relacion([sujeto(['The', attenuated, live, vaccine, strain, 'Bacille', 'Calmette-Guérin', '(', 'BCG),', although]), verbo([providing]), complemento([protection, against, childhood, 'TB,', is, largely, ineffective, against, adult, pulmonary, 'TB'])]). relacion([sujeto(['A', major, aim, therefore, is, to]), verbo([increase]), complemento([the, potency, of, the, 'BCG', vaccine, to, generate, stronger, and, more, sustained, immunity, against, 'TB'])]). relacion([sujeto(['Here,', we, investigated, the, use, of, 'layer-by-layer', '(', 'LbL)', nanocoating, of, the, surface, of, live, 'BCG', with, several, layers, of, 'polyinosinic-polycytidylic', acid, '(', 'poly(I:C)),', a, strong, inducer, of, 'cell-mediated', 'immunity,', and, the, biodegradable, polysaccharide, chitosan, to]), verbo([enhance]), complemento(['BCG', immunogenicity])]). relacion([sujeto(['Nanocoating', of, live, 'BCG', did, not, affect, bacterial, viability, or, growth, 'in vitro', but]), verbo([induced]), complemento([killing, of, the, 'BCG', in, infected, mouse, bone, 'marrow-derived', macrophages, and, enhanced, macrophage, production, of, 'pro-inflammatory', cytokines, and, expression, of, surface, 'co-stimulatory', molecules, relative, to, uncoated, 'BCG'])]). relacion([sujeto(['In', 'addition,', 'poly(I:C)', 'surface-coated', 'BCG,', but, not, 'BCG', alone, or, together, with, soluble, 'poly(I:C),']), verbo([induced]), complemento([high, production, of, nitric, oxide, '(', 'NO)', and, 'IL-12'])]). relacion([sujeto(['These', results, argue, that, 'BCG', and, surface, absorbed, 'poly(I:C)']), verbo([act]), complemento([in, a, synergistic, manner, to, elicit, 'pro-inflammatory', macrophage, activation])]). relacion([sujeto(['In', 'conclusion,', nanocoating, of, live, 'BCG', with, the, immunostimulatory, agent, 'poly(I:C)', may, be, an, appropriate, strategy, to]), verbo([enhance]), complemento([and, modulate, host, responses, to, the, 'BCG', vaccine])]). relacion([sujeto(['The', mammalian, sperm]), verbo([has]), complemento([a, centrally, located, 9, +, 2, arrangement, of, microtubule, doublets, and, hundreds, of, accessory, proteins, that, together, constitute, an, axoneme])]). relacion([sujeto(['These', sheaths, and, the, 'ODFs', add, mechanical, rigidity, to, the, flagellum, creating, the, functional, effect, of]), verbo([increasing]), complemento([bend, 'wavelength,', which, requires, the, entrainment, of, more, dynein, motors, in, the, production, of, a, single, wave])]). relacion([sujeto(['The', sheaths, also]), verbo([act]), complemento([as, a, retinaculum, and, maintain, the, integrity, of, the, central, axoneme, when, large, bending, torques, are, generated, by, dynein])]). relacion([sujeto(['Large', torque, production, is, crucial, to, the, process, of, hyperactivation, and, the, unique, motility, transitions]), verbo([associated]), complemento([with, effective, fertilizing, capacity])]). relacion([sujeto([')', to]), verbo([act]), complemento([as, a, strong, oxidizing, 'agent,', it, was, reacted, with, different, compounds, having, high, ionization, energies])]). relacion([sujeto(['We', show, that, the, 'three-dimensional', '(', 3, 'D)', structure, of, an, 'unstable,', 'low-abundance', enzymatic, intermediate, can, be, determined, by]), verbo([nuclear]), complemento([magnetic, resonance, '(', 'NMR)', spectroscopy])]). relacion([sujeto(['The', approach, is, demonstrated, for, 'Staphylococcus', aureus, sortase, 'A', '(', 'SrtA),', which, is, an, established, drug]), verbo([target]), complemento([and, biotechnological, reagent])]). relacion([sujeto(['The', 3, 'D', structure]), verbo([reveals]), complemento([structural, changes, that, protect, the, thioester, intermediate, against, hydrolysis])]). relacion([sujeto(['A', fundamentally, 'simple,', 'mild,', and, practical, procedure, for, peptide, bond, formation, is]), verbo([reported]), complemento([that, employs, a, stoichiometric, amount, of, 'easy-to-access', 9, -, silafluorenyl, dichlorides, as, the, coupling, agent])]). relacion([sujeto(['Without', initial, preactivation, or, elaboration, of, the, carboxylic, acid, or, amine, termini, of, the, amino, 'acids,', the, developed, reagent, is, proposed, to]), verbo([act]), complemento([through, an, unprecedented, chemical, ligation, 'mechanism,', bringing, the, two, coupling, partners, together, before, being, subsequently, eliminated])]). relacion([sujeto(['But', can, sexual, selection, also, influence, the, 'brain?', 'Previous', studies, in, vertebrates]), verbo([report]), complemento([contradictory, results, with, no, consistent, pattern, between, variation, in, brain, structure, and, the, strength, of, sexual, selection])]). relacion([sujeto(['We', hypothesize, that, sexual, selection, will]), verbo([act]), complemento([in, a, consistent, way, on, two, vertebrate, brain, regions, that, directly, regulate, sexual, 'behaviour:', the, medial, preoptic, nucleus, '(', 'MPON)', and, the, ventromedial, hypothalamic, nucleus, '(', 'VMN)'])]). relacion([sujeto(['The', 'MPON']), verbo([regulates]), complemento([male, reproductive, behaviour, whereas, the, 'VMN', regulates, female, reproductive, behaviour, and, is, also, involved, in, male, aggression])]). relacion([sujeto(['As', the, volumes, of, both, these, regions, also, correlated, with, brain, volume, '(', 'BV)', in, our, 'models,', we, tested, whether, they, show, the, same, pattern, of, evolution, in, response, to, changes, in, 'BV', and]), verbo([found]), complemento([that, the, do])]). relacion([sujeto(['Recently', philosophers]), verbo([have]), complemento([proposed, a, wide, variety, of, interventions, referred, to, as, '\'', moral, 'enhancements\''])]). relacion([sujeto(['Some', of, these, interventions, are, concerned, with, helping, individuals, make, more, informed, 'decisions;', 'others,', 'however,', are, designed, to, compel, people, to]), verbo([act]), complemento([as, the, intervener, sees, fit])]). relacion([sujeto(['Eukaryotic', initiation, factor, 2, 'A', '(', 'eIF2A)', is, a, 65, -, kDa, protein, that, was, first, identified, in, the, early, 1970, s, as, a, factor, capable, of]), verbo([stimulating]), complemento([initiator, 'methionyl-tRNAi', '(', 'Met-tRNA(Met)i)', binding, to, 40, 'S', ribosomal, subunits, in, vitro])]). relacion([sujeto(['However,', in, contrast, to, the, 'eIF2,', which]), verbo([stimulates]), complemento(['Met-tRNA(Met)i', binding, to, 40, 'S', ribosomal, subunits, in, a, 'GTP-dependent', 'manner,', eIF2A, 'didn\'t', reveal, any, 'GTP-dependence,', but, instead, was, found, to, direct, binding, of, the, 'Met-tRNA(Met)i', to, 40, 'S', ribosomal, subunits, in, a, 'codon-dependent', manner])]). relacion([sujeto([eIF2A, appears, to, be, highly]), verbo([conserved]), complemento([across, eukaryotic, 'species,', suggesting, conservation, of, function, in, evolution])]). relacion([sujeto(['The', yeast, 'Saccharomyces', cerevisae, eIF2A, null, mutant, revealed, no, apparent, 'phenotype,', 'however,', it, was]), verbo([found]), complemento([that, in, yeast, eIF2A, functions, as, a, suppressor, of, internal, ribosome, entry, site, '(', 'IRES)-mediated', translation])]). relacion([sujeto(['It', was, thus]), verbo([suggested]), complemento([that, eIF2A, my, act, by, impinging, on, the, expression, of, specific, mRNAs])]). relacion([sujeto(['Subsequent', studies, in, mammalian, cell, systems, implicated, eIF2A, in, 'non-canonical', '(', 'non-AUG-dependent)', translation, initiation, events]), verbo([involving]), complemento([near, cognate, 'UUG', and, 'CUG', codons])]). relacion([sujeto(['As', a, first, step, toward, characterization, of, the, eIF2A, function, in, mammalian, systems, in, 'vivo,', we]), verbo([have]), complemento([obtained, homozygous, 'eIF2A-total', knockout, '(', 'KO)', 'mice,', in, which, a, gene, trap, cassette, was, inserted, between, eIF2A, exons, 1, and, 2, disrupting, expression, of, all, exons, downstream, of, the, insertion])]). relacion([sujeto(['A', carbonylcobalt, 'catalyst,', immobilized, by, 'poly(4-vinylpyridine)', '(', 'P4VP)', through, 'N→Co', coordination, 'bonds,']), verbo([has]), complemento([been, prepared, by, solvothermal, method])]). relacion([sujeto(['It']), verbo([has]), complemento([been, revealed, that, the, pyridine, fragments, in, the, polymer, catalyst, act, not, only, as, promoters, to, improve, the, catalytic, performance, of, the, carbonylcobalt, catalyst, for, alkoxycarbonylation, of, ethylene, oxide, to, methyl, 3, -, hydroxypropanoate, but, also, as, stabilizers, to, enhance, the, reusability, of, the, polymer, catalyst])]). relacion([sujeto(['Furthermore,', the, polymer, catalyst, could, be, easily, separated, by, filtration, and, reused, with, only, a, slight]), verbo([loss]), complemento([of, catalytic, efficiency])]). relacion([sujeto(['Ecological', opportunity, afforded, by, invasion, of, a, new, habitat, is, thought, to]), verbo([act]), complemento([as, an, ecological, 'release,', facilitating, 'divergence,', and, speciation])]). relacion([sujeto(['Comparison', with, an, outgroup, taxon]), verbo([reveals]), complemento(['large-scale', ecomorphological, divergence, but, shallow, genomic, differentiation, within, the, 'Alcolapia', adaptive, radiation])]). relacion([sujeto(['Ancestral', morphological, reconstruction]), verbo([suggests]), complemento([lake, colonization, by, a, generalist, oreochromine, phenotype, that, diverged, in, 'Lake', 'Natron', to, varied, herbivorous, morphologies, akin, to, specialist, herbivores, in, 'Lakes', 'Tanganyika', and, 'Malawi'])]). relacion([sujeto(['The', prevalence, of, eating, 'disorders,', such, as, anorexia, 'nervosa,', binge, eating, and, 'obesity,', poses, an, enormous, clinical, 'burden,', and]), verbo([involves]), complemento([an, 'ever-growing', percentage, of, the, population, worldwide])]). relacion([sujeto(['Clinical', and, preclinical, research, is, constantly, adding, new, information, to, the, field, and, orienting, further, studies, with, the, aim, of]), verbo([providing]), complemento([a, foundation, for, developing, more, specific, and, effective, treatment, approaches, to, pathological, conditions])]). relacion([sujeto(['The', 'gut-brain', axis]), verbo([has]), complemento([received, increasing, attention, in, the, recent, years, as, preclinical, studies, are, demonstrating, that, the, brain, and, visceral, organs, such, as, the, liver, and, 'guts,', but, also, the, microbiota, are, constantly, engaged, in, processes, of, reciprocal, 'communication,', with, unexpected, physiological, and, pathological, implications])]). relacion([sujeto(['Eating', is, controlled, by, a, plethora, of, 'factors;', genetic, 'predisposition,', early, life, adverse, 'conditions,', peripheral, gastrointestinal, hormones, that]), verbo([act]), complemento([directly, or, indirectly, on, the, central, nervous, 'system,', all, are, receiving, attention, as, they, presumably, contribute, to, the, development, of, eating, disorders])]). relacion([sujeto(['Plant', aromatic, compounds]), verbo([provide]), complemento([signals, and, a, nutrient, source, to, 'pathogens,', and, also, act, as, stressors])]). relacion([sujeto(['Structure-activity', relationships]), verbo([suggest]), complemento([two, pathways, sensing, these, compounds, in, the, maize, pathogen, 'Cochliobolus', 'heterostrophus,', one, triggering, a, stress, 'response,', and, one, inducing, enzymes, for, their, degradation])]). relacion([sujeto(['Focusing', on, the, stress, 'pathway,', we]), verbo([found]), complemento([that, ferulic, acid, causes, rapid, appearance, of, 'TUNEL-positive', 'nuclei,', dispersion, of, histone, 'H1:GFP,', hyphal, 'shrinkage,', and, eventually, membrane, damage])]). relacion([sujeto(['Exposure', to, ferulic, acid, dephosphorylated, two, 'MAP', 'kinases:', 'Hog1', '(', stress, 'activated)', and, 'Chk1', '(', pathogenicity, 'related),', while]), verbo([increasing]), complemento([phosphorylation, of, 'Mps1', '(', cell, integrity, 'related)'])]). relacion([sujeto(['Ferulic', acid, and, the, antifungal, fludioxonil]), verbo([have]), complemento([opposite, additive, effects, on, survival, and, on, dephosphorylation, of, 'Hog1,', which, is, thus, implicated, in, survival])]). relacion([sujeto(['The', results, may, explain, why, some, fungal, pathogens, of, plants, undergo, cell, death, early, in, host, 'invasion,', when, phenolics, are]), verbo([released]), complemento([from, plant, tissue])]). relacion([sujeto(['A', high, occurrence, of, strains, harbouring, hemolysin, genes, was, also]), verbo([found]), complemento([in, both, species])]). relacion([sujeto(['This', study, gives, a, first, and, extensive, picture, of, 'safety-related', properties, within, 'Staphylococcus', species, isolated, from, milk, of, healthy, 'goats,', displaying, that, these, species, can]), verbo([act]), complemento([as, a, reservoir, for, spreading, genes, related, to, safety])]). relacion([sujeto(['Taking', advantage, of, antibody, molecules, to, generate, 'tailor-made']), verbo([binding]), complemento(['sites,', we, propose, a, new, class, of, protein, 'modifications,', termed, as, &, 'quot;site-directed', chemical, mutation])]). relacion([sujeto([&, 'quot;', 'In', this, 'modification,', chemically, synthesized, catalytic, components, with, a, variety, of, steric, and, electronic, properties, can, be, noncovalently, and, nongenetically, incorporated, into, specific, sites, in, antibody, molecules, to]), verbo([induce]), complemento([enzymatic, activity])]). relacion([sujeto(['Two', catalytic, 'antibodies,', 2500.0, and, 27, 'C1,', possess, 'antigen-combining', sites, which]), verbo([bind]), complemento([catalytic, components, and, act, as, apoproteins, in, catalytic, reactions])]). relacion([sujeto(['In', this, 'work,', we, focused, on, the, 'β-elimination', reaction, and, examined, the, 'site-directed', chemical, mutation, of, 27, 'C1', to]), verbo([induce]), complemento([activity, and, elucidate, the, catalytic, mechanism])]). relacion([sujeto(['This']), verbo([suggested]), complemento([that, during, 'β-elimination,', 'Arg(H52)', of, 27, 'C1', would, form, a, salt, bridge, with, the, carboxylate, of, 4, ',', thus, destroying, reactivity])]). relacion([sujeto(['It', is, noteworthy, that, chemical, mutation, with, secondary, amine, 8]), verbo([provided]), complemento([extremely, high, 'activity,', with, a, rate, acceleration, '[', '(', 'kcat/Km', 2, ')', /, 'kuncat]', of, 1, ' 000 000'])]). relacion([sujeto(['This', catalytic, activity, likely, arises, from, the, proximity, 'effect,', plus, 'general-base', catalysis]), verbo([associated]), complemento([the, electrostatic, interactions])]). relacion([sujeto(['Thus,', 'site-directed', chemical, mutation]), verbo([provides]), complemento([a, better, understanding, of, enzyme, functions, and, opens, new, avenues, in, biocatalyst, research])]). relacion([sujeto(['The', 'Androgen', 'Receptor', '(', 'AR)', remains, the]), verbo([leading]), complemento([target, of, advanced, prostate, cancer, therapies])]). relacion([sujeto(['Thiosalicylamide', analogs]), verbo([have]), complemento([previously, been, shown, to, act, in, cells, as, acyltransfer, catalysts, that, are, capable, of, transferring, cellular, 'acetate,', presumably, from, 'acetyl-CoA,', to, 'HIV', 'NCp7'])]). relacion([sujeto(['Here', we, explore, if, the, cellular, 'acetyl-transfer', activity, of, thiosalicylamides, can, be, redirected, to, other, cellular]), verbo([targets]), complemento([guided, by, ligands, for, 'AR'])]). relacion([sujeto(['We', constructed, conjugates, of, thiosalicylamides, and, the, 'AR-binding', small, molecule, tolfenamic, 'acid,', which]), verbo([binds]), complemento([the, 'BF-3', site, of, 'AR,', proximal, to, the, coactivator, &, 'quot;FXXLF"', binding, surface])]). relacion([sujeto(['The', 'thiosalicylamide-tolfenamic', acid, 'conjugate,', 'YZ03,', but, not, the, separate, thiosalicylamide, plus, tolfenamic, 'acid,', significantly]), verbo([enhanced]), complemento([acetylation, of, endogenous, 'AR', in, 'CWR22Rv1', cells])]). relacion([sujeto(['Under', 'acyl-transfer', 'conditions,', 'YZ03', significantly]), verbo([enhances]), complemento([the, ability, of, 'BF-3', site, binding, ligands, to, inhibit, 'AR-coactivator', peptide, association])]). relacion([sujeto(['These', data]), verbo([suggest]), complemento([that, biomimetic, acyltransferases, can, enhance, 'protein-protein', interaction, inhibitors, through, covalent, modification, of, critical, interfacial, residues])]). relacion([sujeto(['Participating', physicians, significantly]), verbo([increased]), complemento([the, proportion, of, well, visits, in, which, they, spent, time, alone, with, the, patient, '(', 'P = '])]). relacion([sujeto(['This', receptor]), verbo([acts]), complemento([to, regulate, calcium, and, phosphate, 'homeostasis,', as, well, as, bone, turnover, and, development])]). relacion([sujeto(['N-terminally', truncated, derivatives, of, 'PTH(1-34),', such, as, 'PTH(7-34),', are, known, to]), verbo([bind]), complemento([to, 'PTHR1', without, initiating, intracellular, signaling, and, can, thus, act, as, competitive, antagonists, of, 'PTH-induced', signaling, at, 'PTHR1'])]). relacion([sujeto(['In', some, 'cases,', 'N-terminally', truncated, 'PTH', derivatives, also]), verbo([act]), complemento([as, inverse, agonists, of, 'PTHR1', variants, that, display, pathologically, high, levels, of, signaling, in, the, absence, of, 'PTH'])]). relacion([sujeto(['We', show, that, backbone, modification, via, periodic, replacement, of, 'α-amino', acid, residues, with, homologous, 'β-amino', acid, residues]), verbo([leads]), complemento([to, an, 'α/β-PTH(7-34)', peptide, that, retains, the, antagonist, and, inverse, agonist, activities, of, the, prototype, 'α-peptide', while, exhibiting, enhanced, stability, in, the, presence, of, aggressive, proteases])]). relacion([sujeto(['These', findings, highlight, the, value, of, 'backbone-modified', peptides, derived, from, 'PTH', as, tools, for, investigating, determinants, of, 'PTH', metabolism, and]), verbo([provide]), complemento([guidance, for, designing, therapeutic, agents, for, diseases, arising, from, excessive, 'ligand-dependent', or, 'ligand-independent', 'PTHR1', activity])]). relacion([sujeto(['Angiopoietin-like', protein, 1, '(', 'ANGPTL1)']), verbo([has]), complemento([been, shown, to, act, as, a, tumor, suppressor, by, inhibiting, 'angiogenesis,', cancer, 'invasion,', and, metastasis])]). relacion([sujeto(['ANGPTL1', significantly]), verbo([decreases]), complemento(['epithelial-mesenchymal', transition, '(', 'EMT)-driven', sorafenib, 'resistance,', cancer, 'stemness,', and, tumor, growth, of, 'HCC', cells, by, repressing, 'Slug', expression])]). relacion([sujeto(['ANGPTL1', directly]), verbo([interacts]), complemento([with, and, inactivates, 'MET', 'receptor,', which, contributes, to, 'Slug', suppression, through, inhibition, of, the, extracellular, receptor, 'kinase/protein', kinase, 'B', '(', 'ERK/AKT)-dependent', early, growth, response, protein, 1, '(', 'Egr-1)', pathway])]). relacion([sujeto(['ANGPTL1']), verbo([inhibits]), complemento([sorafenib, resistance, and, cancer, stemness, in, 'HCC', cells, by, repressing, 'EMT', through, inhibition, of, the, 'MET', 'receptor-AKT/ERK-Egr-1-Slug', signaling, cascade])]). relacion([sujeto(['Sweet', cherries, are, highly, appreciated, by, consumers, worldwide, and, are, usually, 'cold-stored', during, postharvest, to]), verbo([prevent]), complemento(['over-ripening', before, distribution, to, the, market])]). relacion([sujeto(['Sweet', cherry, is, a, 'non-climacteric', 'fruit,', for, which, ripening, is, known, to, be]), verbo([regulated]), complemento([by, abscisic, acid])]). relacion([sujeto(['Hormonal', profiling, revealed, that, 'indole-3-acetic', 'acid,', 'GA1', and, 'trans-zeatin', levels]), verbo([decreased]), complemento([at, early, stages, of, fruit, 'development,', while, 'GA3', levels, decreased, at, early, stages, but, also, 'later,', once, anthocyanin, accumulation, started])]). relacion([sujeto(['Conversely,', abscisic, acid, levels, rose, significantly, once, the, fruit, started, to, synthetize, 'anthocyanins,', and, isopentenyladenosine, levels, also]), verbo([increased]), complemento([during, the, ripening, of, sweet, cherries])]). relacion([sujeto(['A', strong, negative, correlation, was]), verbo([found]), complemento([between, 'GA4', levels, and, both, fruit, biomass, and, anthocyanin, 'levels,', and, between, the, levels, of, 'trans-zeatin', and, both, fruit, biomass, and, total, sugar, contents])]). relacion([sujeto(['Results']), verbo([suggest]), complemento([that, 'auxins,', cytokinins, and, gibberellins, may, act, coordinately, with, abscisic, acid, in, the, regulation, of, sweet, cherry, development, and, ripening])]). relacion([sujeto(['Furthermore,', it, is, shown, that, hormonal, profile, measurements, by, 'UHPLC-MS/MS', may, be, a, helpful, tool, to, elucidate, the, timing, of, action, of, each, specific, hormonal, compound, during, 'ripening,', which]), verbo([has]), complemento([important, applications, in, the, 'agri-food', biotechnological, sector])]). relacion([sujeto(['These', are, compounds, that]), verbo([have]), complemento([little, or, no, antibiotic, activity, themselves, but, act, to, block, resistance, or, otherwise, enhance, antibiotic, action])]). relacion([sujeto(['Antibiotic', adjuvants, are, therefore, delivered, in, combination, with, antibiotics, and, can, be, divided, into, two, 'groups:', 'Class', 'I', agents, that]), verbo([act]), complemento([on, the, 'pathogen,', and, 'Class', 'II', agents, that, act, on, the, host])]). relacion([sujeto(['Adjuvants', offer, a, means, to, both]), verbo([suppress]), complemento([the, emergence, of, resistance, and, rescue, the, activity, of, existing, 'drugs,', offering, an, orthogonal, strategy, complimentary, to, new, antibiotic, discovery, 'VIDEO', 'ABSTRACT'])]). relacion([sujeto(['As', part, of, the, 'National', 'Institute', for, 'Health', and, 'Clinical', 'Excellence', '(', 'NICE)', single, technology, appraisal, '(', 'STA)', 'process,', the, manufacturer, of, apremilast, was, invited, to, submit, evidence, for, its, clinical, and, cost, effectiveness, for, the, treatment, of, active, psoriatic, arthritis, '(', 'PsA)', for, whom, 'disease-modifying', 'anti-rheumatic', drugs, '(', 'DMARDs)']), verbo([have]), complemento([been, inadequately, 'effective,', not, tolerated, or, contraindicated])]). relacion([sujeto(['The', 'Centre', for, 'Reviews', and, 'Dissemination', and, 'Centre', for, 'Health', 'Economics', at, the, 'University', of, 'York', were, commissioned, to]), verbo([act]), complemento([as, the, independent, 'Evidence', 'Review', 'Group', '(', 'ERG)'])]). relacion([sujeto(['This', paper]), verbo([provides]), complemento([a, description, of, the, 'ERG', review, of, the, 'company\'s', 'submission,', the, 'ERG', report, and, submission, and, summarises, the, 'NICE', 'Appraisal', 'Committee\'s', subsequent, guidance, '(', 'December', 2015, ')'])]). relacion([sujeto(['Furthermore,', assumptions, made, regarding, a, potential, beneficial, effect, of, apremilast, on, 'long-term', 'Health', 'Assessment', 'Questionnaire', '(', 'HAQ)', 'progression,', which, cannot, be, 'substantiated,']), verbo([have]), complemento([a, very, significant, impact, on, results])]). relacion([sujeto(['The', 'AC', thus, decided, that, apremilast, alone, or, in, combination, with, 'DMARD', therapy, is, not, recommended, for, treating, adults, with, active, 'PsA', that]), verbo([has]), complemento([not, responded, to, prior, 'DMARD', 'therapy,', or, where, such, therapy, is, not, tolerated])]). relacion([sujeto(['Our', objective, was, to, project, the, characteristics, and, number, of, people, needing, antiviral, treatment, and, 'HCV-associated', disease, burden, in, the]), verbo([era]), complemento([of, oral, 'DAAs'])]). relacion([sujeto(['HCV-associated', disease, burden, will, still, remain, substantial, in, the]), verbo([era]), complemento([of, oral, 'DAAs'])]). relacion([sujeto(['Increasing', 'HCV', screening, and, treatment, capacity, is, essential, to, further]), verbo([decreasing]), complemento(['HCV', burden, in, the, 'United', 'States'])]). relacion([sujeto(['Compared', with, 'patients,', clinicians]), verbo([required]), complemento([similar, survival, time, benefits, '(', medians, both, 1, 'year,', 'P=0'])]). relacion([sujeto(['NET', '(', 'NocA/Nlz,', 'Elbow,', 'Tlp-1)', family, members]), verbo([have]), complemento([recently, emerged, as, important, players, in, the, development, of, human, cancers])]). relacion([sujeto(['Both', in, vitro, and, in, vivo, studies, demonstrated, that, 'ZNF703', could, potently]), verbo([promote]), complemento(['proliferation,', migration, and, invasion, throughout, the, progression, of, 'CCA'])]). relacion([sujeto(['ZNF703', can, potently, facilitate, tumor, growth, and, metastasis, in, many, respects, throughout, the, progression, of, 'CCA,', which, may]), verbo([act]), complemento([as, an, oncogene, in, 'CCA', and, can, be, considered, as, a, novel, potential, therapeutic, target])]). relacion([sujeto(['Endometrial', cancer, tissues, and, cell, lines, exhibited]), verbo([increased]), complemento(['PAX2', expression, compared, with, 'hyperplasia,', normal, endometrium, and, endometrial, epithelial, cells])]). relacion([sujeto(['Knock-down', of, 'PAX2', resulted, in, reduced, cell, 'viability,', invasion, and, 'migration,', and, 'PAX2', overexpression]), verbo([caused]), complemento([the, opposite, effects])]). relacion([sujeto(['Knock-down', of, 'MZF1', 'up-regulated', the, transcriptional, activity, and, protein, level, of, 'PAX2', after, 5, -, 'Aza-CdR', 'treatment,', which, indicated, that, 'MZF1', may]), verbo([act]), complemento([as, a, repressive, transcription, factor, when, the, 'PAX2', promoter, is, unmethylated])]). relacion([sujeto(['In', 'conclusion,', 'PAX2', is]), verbo([involved]), complemento([in, the, carcinogenesis, of, endometrial, cancer, by, stimulating, cell, growth, and, promoting, cell, motility])]). relacion([sujeto(['The', overexpression, of, 'PAX2', in, endometrial, cancer, is]), verbo([regulated]), complemento([by, promoter, hypermethylation, and, the, transcription, factor, 'MZF1'])]). relacion([sujeto(['Gefitinib', is, an, oral, 'EGFR', tyrosine, kinase, inhibitors, which, may]), verbo([act]), complemento([as, a, radiosensitizer])]). relacion([sujeto(['Human', 'CUB', and, 'Sushi', multiple, domains, 1, '(', 'CSMD1)', is, a, 'membrane-bound', complement, inhibitor]), verbo([suggested]), complemento([to, act, as, a, putative, tumor, suppressor, 'gene,', since, allelic, loss, of, this, region, encompassing, 8, p23, including, 'CSMD1', characterizes, various, malignancies])]). relacion([sujeto(['We']), verbo([found]), complemento([that, human, breast, tumor, tissues, expressed, 'CSMD1', at, lower, levels, compared, to, that, in, normal, mammary, tissues])]). relacion([sujeto(['The']), verbo([decreased]), complemento([expression, of, 'CSMD1', was, linked, to, a, shorter, overall, survival, of, breast, cancer, patients])]). relacion([sujeto(['We', also, revealed, that, expression, of, 'CSMD1', in, human, breast, cancer, cells, 'BT-20', and, 'MDA-MB-231', significantly]), verbo([inhibited]), complemento([their, malignant, 'phenotypes,', including, 'migration,', adhesion, and, invasion])]). relacion([sujeto(['Conversely,', stable, silencing, of, 'CSMD1', expression, in, 'T47D', cells]), verbo([enhanced]), complemento([cancer, cell, 'migratory,', adherent, and, clonogenic, abilities])]). relacion([sujeto(['In', a, xenograft, 'model,', expression, of, 'CSMD1', blocked, the, ability, of, cancer, cells, to, metastasize, to, secondary, sites, in, 'vivo,', likely, via]), verbo([inhibiting]), complemento([local, invasion, but, not, the, extravasation, into, distant, tissues])]). relacion([sujeto(['The', results]), verbo([suggest]), complemento([that, cell, proliferation, was, markedly, decreased, in, 'NaMoS-treated', groups, '(', 1, ',', 10, ',', 25, ',', 50, ',', 100, ',', 500, ',', 1000, 'μM)', in, a, 'dose-dependent', manner, compared, with, the, 'Control', group, and, the, 'IC50', was, 221.67, μM, at, 48, h])]). relacion([sujeto(['NaMoS', at, 200, μM, concentration, significantly]), verbo([inhibited]), complemento([the, invasion, and, promoted, apoptosis, of, 'B16F10', cells])]). relacion([sujeto(['Moreover,', protein, level, of, 'Caspase3']), verbo([increased]), complemento([significantly, in, 'B16F10', cells, treated, by, 'NaMoS'])]). relacion([sujeto(['Immunohistochemistry', and, 'Western', blot, further, confirmed, that, 'NaMoS']), verbo([decreased]), complemento([the, expression, of, 'vimentin,', 'MMP9,', 'p-Akt1/2/3', and, 'p-ERK1/2', in, 'B16F10', cells])]). relacion([sujeto(['This', study]), verbo([provides]), complemento([robust, evidence, that, 'NaMoS,', a, 'water-soluble', 'flavonoid,', manifests, anticancer, properties, and, may, act, as, a, signal, transduction, inhibitor, in, melanoma, cells])]). relacion([sujeto(['A', comprehensive, series, of]), verbo([nuclear]), complemento([tests, were, carried, out, by, the, 'United', 'States', at, 'Enewetak', 'Atoll', in, the, 'Marshall', 'Islands,', especially, between, 1952, and, 1958])]). relacion([sujeto(['Here', we]), verbo([report]), complemento([measurements, of, '(', 236, ')', 'U', and, '(', 239, ',', 240, ')', 'Pu', on, the, same, coral, using, accelerator, mass, 'spectrometry,', and, again, find, prominent, peaks, in, the, concentrations, of, these, isotopes, that, closely, follow, those, in, '(', 14, ')', 'C'])]). relacion([sujeto(['Additional', information, about, the, different, tests, can, also, be, obtained, from, the, '(', 236, ')', 'U/(239)Pu', and, '(', 240, ')', 'Pu/(239)Pu', 'ratios,', which, are]), verbo([found]), complemento([to, vary, dramatically, over, the, testing, period])]). relacion([sujeto(['In', 'particular,', the, first, thermonuclear, 'test,', 'Ivy-Mike,']), verbo([has]), complemento([characteristic, '(', 236, ')', 'U/(239)Pu', and, '(', 240, ')', 'Pu/(239)Pu', signatures, which, are, diagnostic, of, the, first, arrival, of, nuclear, test, material, in, various, archives])]). relacion([sujeto(['Autophagy', is, an, important, antimicrobial, effector, process, that, defends, against, 'Mycobacterium', tuberculosis, '(', 'Mtb),', the, human, pathogen]), verbo([causing]), complemento([tuberculosis, '(', 'TB)'])]). relacion([sujeto(['MicroRNAs', '(', 'miRNAs),', endogenous, noncoding, 'RNAs,', are]), verbo([involved]), complemento([in, various, biological, functions, and, act, as, 'post-transcriptional', regulators, to, target, mRNAs])]). relacion([sujeto(['In', this, 'study,', we, show, that, 'Mtb', significantly]), verbo([induces]), complemento([the, expression, of, 'MIR144*/hsa-miR-144-5p,', which, targets, the, 3, '\'', -, untranslated, region, of, 'DRAM2', '(', 'DNA', damage, regulated, autophagy, modulator, 2, ')', in, human, monocytes, and, macrophages])]). relacion([sujeto(['Mtb', infection, 'downregulated,', whereas, the, autophagy, activators, 'upregulated,', 'DRAM2', expression, in, human, monocytes, and, macrophages, by]), verbo([activating]), complemento(['AMP-activated', protein, kinase])]). relacion([sujeto(['In', 'addition,', overexpression, of, 'MIR144*']), verbo([decreased]), complemento(['DRAM2', expression, and, formation, of, autophagosomes, in, human, 'monocytes,', whereas, inhibition, of, 'MIR144*', had, the, opposite, effect])]). relacion([sujeto(['Notably,', 'DRAM2']), verbo([interacted]), complemento([with, 'BECN1', and, 'UVRAG,', essential, components, of, the, autophagic, 'machinery,', leading, to, displacement, of, 'RUBCN', from, the, 'BECN1', complex, and, enhancement, of, 'Ptdlns3K', activity])]). relacion([sujeto(['Furthermore,', 'MIR144*', and, 'DRAM2', were, critically]), verbo([involved]), complemento([in, phagosomal, maturation, and, enhanced, antimicrobial, effects, against, 'Mtb'])]). relacion([sujeto(['Additionally,', these, data]), verbo([reveal]), complemento([that, 'DRAM2', is, a, key, coordinator, of, autophagy, activation, that, enhances, antimicrobial, activity, against, 'Mtb'])]). relacion([sujeto(['The', phospholipid, cardiolipin, '(', 'CL)']), verbo([has]), complemento([been, proposed, to, play, a, role, in, selective, mitochondrial, 'autophagy,', or, mitophagy])]). relacion([sujeto(['CL', externalization, to, the, outer, mitochondrial, membrane, would]), verbo([act]), complemento([as, a, signal, for, the, human, 'Atg8', ortholog, 'subfamily,', 'MAP1LC3', '(', 'LC3)'])]). relacion([sujeto(['The', latter, would]), verbo([mediate]), complemento([both, mitochondrial, recognition, and, autophagosome, 'formation,', ultimately, leading, to, removal, of, damaged, mitochondria])]). relacion([sujeto(['We']), verbo([have]), complemento([applied, quantitative, biophysical, techniques, to, the, study, of, 'CL', interaction, with, various, 'Atg8', human, 'orthologs,', namely, 'LC3B,', 'GABARAPL2', and, 'GABARAP'])]). relacion([sujeto(['We']), verbo([have]), complemento([found, that, 'LC3B', interacts, preferentially, with, 'CL', over, other, 'di-anionic', 'lipids,', that, 'CL-LC3B', binding, occurs, with, positive, 'cooperativity,', and, that, the, 'CL-LC3B', interaction, relies, only, partially, on, electrostatic, forces])]). relacion([sujeto(['CL-induced']), verbo([increased]), complemento([membrane, fluidity, appears, also, as, an, important, factor, helping, 'LC3B', to, bind, 'CL'])]). relacion([sujeto(['The', 'LC3B', 'C', terminus, remains, exposed, to, the, hydrophilic, environment, after, protein]), verbo([binding]), complemento([to, 'CL-enriched', membranes])]). relacion([sujeto(['In', intact, 'U87MG', human, glioblastoma, cells, 'rotenone-induced', autophagy]), verbo([leads]), complemento([to, 'LC3B', translocation, to, mitochondria, and, subsequent, delivery, of, mitochondria, to, lysosomes])]). relacion([sujeto(['We']), verbo([have]), complemento([also, observed, that, 'GABARAP,', but, not, 'GABARAPL2,', interacts, with, 'CL', in, vitro])]). relacion([sujeto(['Activated', 'FXI', '(', 'FXIa)']), verbo([promotes]), complemento([thrombin, generation, by, enzymatic, activation, of, 'FXI,', 'FIX,', 'FX,', and, 'FV,', and, inactivation, of, alpha, tissue, factor, pathway, inhibitor, '(', 'TFPIα),', in, vitro])]). relacion([sujeto(['Some', of, these, reactions, are, now, known, to, be]), verbo([enhanced]), complemento([by, 'short-chain', polyphosphates, '(', 'SCP)', derived, from, activated, platelets])]). relacion([sujeto(['These', 'SCPs']), verbo([act]), complemento([as, a, cofactor, for, the, activation, of, 'FXI', and, 'FV', by, thrombin, and, 'FXIa,', respectively])]). relacion([sujeto(['Since', 'SCPs']), verbo([have]), complemento([been, shown, to, inhibit, the, anticoagulant, function, of, 'TFPIα,', we, herein, investigated, whether, 'SCPs', could, serve, as, cofactors, for, the, proteolytic, inactivation, of, 'TFPIα', by, 'FXIa,', further, promoting, the, efficiency, of, the, extrinsic, pathway, of, coagulation, to, generate, thrombin])]). relacion([sujeto(['Our', data]), verbo([suggest]), complemento([that, 'SCP', is, a, cofactor, for, 'TFPIα', inactivation, by, 'FXIa,', 'thus,', expanding, the, range, of, hemostatic, 'FXIa', substrates, that, may, be, affected, by, the, cofactor, functions, of, 'platelet-derived', 'SCP'])]). relacion([sujeto(['Management', authorities, seldom]), verbo([have]), complemento([the, capacity, to, comprehensively, address, the, full, suite, of, anthropogenic, 'stressors,', particularly, in, the, coastal, zone, where, numerous, threats, can, act, simultaneously, to, impact, reefs, and, other, ecosystems])]). relacion([sujeto(['This', situation]), verbo([requires]), complemento([tools, to, prioritise, management, interventions, that, result, in, optimum, ecological, outcomes, under, a, set, of, constraints])]). relacion([sujeto(['Empirical', field, data, was, used, to, model, a, suite, of, possible, ecological, responses, of, coral, reef, assemblages, to, five, key, management, actions, both, in, the]), verbo([sea]), complemento(['(', e])]). relacion([sujeto(['Heightened', fishing, 'restrictions,', restoring, 'habitats,', and, reducing, nutrient, discharges, from, wastewater, treatment, plants]), verbo([have]), complemento(['additional,', albeit, smaller, effects])]). relacion([sujeto(['The', method, presented, here]), verbo([provides]), complemento([a, useful, tool, to, prioritize, environmental, actions, in, situations, where, multiple, competing, management, interventions, exist, for, coral, reefs, and, in, other, systems, subjected, to, multiple, stressor, from, the, land, and, the, sea])]). relacion([sujeto(['In', the, central, nervous, system, '(', 'CNS),', activation, of, the, transcription, factor]), verbo([nuclear]), complemento(['factor-kappa', 'B', '(', 'NF-κβ)', is, associated, with, both, neuronal, survival, and, increased, vulnerability, to, apoptosis])]). relacion([sujeto(['In', 'Alzheimer\'s', disease, '(', 'AD),', 'β-amyloid', '(', 'Aβ)', and, other, aggregates, upregulate, activation, of, 'p65:p50', dimers, in, 'CNS', cells, and]), verbo([enhance]), complemento([transactivation, of, pathological, mediators, that, cause, neuroinflammation, and, neurodegeneration])]). relacion([sujeto(['Hence', selective]), verbo([targeting]), complemento([of, activated, p65, is, an, attractive, therapeutic, strategy, for, 'AD'])]). relacion([sujeto(['Here', we]), verbo([report]), complemento([the, 'design,', structural, and, functional, characterization, of, peptide, analogs, of, a, p65, interacting, 'protein,', the, glucocorticoid, induced, leucine, zipper, '(', 'GILZ)'])]). relacion([sujeto(['By', virtue, of]), verbo([binding]), complemento([the, transactivation, domain, of, p65, exposed, after, release, from, the, inhibitory, 'IκΒ', proteins, in, activated, 'cells,', the, 'GILZ', analogs, can, act, as, highly, selective, inhibitors, of, activated, p65, with, minimal, potential, for, 'off-target', effects])]). relacion([sujeto(['In', 2006, ',', 65, '%', of, women, had, 'Medicaid,', 18, '%', had, private, 'insurance,', 3, '%', had, 'Medicare', or, other, public, 'insurance,', and, 14, '%']), verbo([reported]), complemento([no, health, insurance])]). relacion([sujeto(['ADAP', coverage, was]), verbo([reported]), complemento([by, 284, women, '(', 20, '%', ')', ;, 56, '%', of, uninsured, participants, reported, 'ADAP', coverage])]). relacion([sujeto(['Continued', support, of, this, program, may, be, especially, critical, for, states, that]), verbo([have]), complemento([not, expanded, 'Medicaid'])]). relacion([sujeto(['The', recent]), verbo([increase]), complemento([in, the, creation, of, transboundary, protected, areas, and, wildlife, corridors, between, them, lends, importance, to, information, on, pathogen, prevalence, and, transmission, among, wildlife, species, that, will, become, connected])]). relacion([sujeto(['High', antibody, prevalence, '(', &, 'gt;90%)', was, only]), verbo([found]), complemento([to, 'FHV-1', and, 'FIV', in, lions])]). relacion([sujeto(['Among', children, aged, 4, -, 11, 'years,', the, 'C-ACT']), verbo([requires]), complemento([the, simultaneous, presence, of, both, parent, and, child])]). relacion([sujeto(['In', this, 'review,']), verbo([reports]), complemento([were, retrieved, in, which, vitamin, 'D', 'status,', as, assessed, by, serum, 25, -, hydroxyvitamin, 'D', '[', 25, '(', 'OH)D]', 'levels,', was, measured, in, 'South', 'African', population, groups, with, varied, skin, colours, and, ethnicities])]). relacion([sujeto(['With', regard, to, disease, 'susceptibility,', 11, of, 22, relevant, publications, indicated, association, between, low, 25, '(', 'OH)D', levels, and, 'disease,', with, deficiency, most, notably]), verbo([found]), complemento([in, individuals, with, tuberculosis, and, 'HIV-1'])]). relacion([sujeto(['Whether', vitamin, 'D', plays, an, important, role, in, protection, against, the, range, of, diseases, that, currently, constitute, a, large, burden, on, the, health, services, in, 'South', 'Africa']), verbo([requires]), complemento([further, investigation])]). relacion([sujeto(['Emerging', studies, show, that, dysregulation, of, the, receptor, of]), verbo([activated]), complemento([protein, kinase, 'C1', '(', 'RACK1)', plays, a, crucial, role, in, tumorigenesis, and, progression, of, various, cancers])]). relacion([sujeto(['Here,', we]), verbo([found]), complemento([that, 'RACK1', was, significantly, 'up-regulated', in, glioma, tissues, compared, with, normal, brain, 'tissues,', being, closely, related, to, clinical, stage, of, glioma, both, in, mRNA, and, protein, levels])]). relacion([sujeto(['In', vitro, functional, assays, indicated, that, silencing, of, 'RACK1', could, dramatically]), verbo([promote]), complemento([apoptosis, and, inhibit, cell, 'proliferation,', 'migration,', and, invasion, of, glioma, cells])]). relacion([sujeto(['More', 'importantly,', knockdown, of, 'RACK1']), verbo([led]), complemento([to, a, vast, accumulation, of, cells, in, 'G0/G1', phase, and, their, reduced, proportions, at, the, 'S', phase, by, suppressing, the, expression, of, 'G1/S', transition, key, regulators, 'Cyclin', 'D1', and, 'CDK6'])]). relacion([sujeto(['Additionally,', this, forced, 'down-regulation', of, 'RACK1', significantly]), verbo([suppressed]), complemento([migration, and, invasion, via, inhibiting, the, 'epithelial-mesenchymal', transition, '(', 'EMT)', 'markers,', such, as, 'MMP2,', 'MMP9,', 'ZEB1,', 'N-Cadherin,', and, 'Integrin-β1'])]). relacion([sujeto(['Collectively,', our, study, revealed, that, 'RACK1', might]), verbo([act]), complemento([as, a, valuable, prognostic, biomarker, and, potential, therapeutic, target, for, glioma])]). relacion([sujeto(['The', complex, '[', 'Os(btzpy)₂][PF₆]₂', '(', 1, ',', btzpy, =, 2, ',', 6, -, 'bis(1-phenyl-1,2,3-triazol-4-yl)pyridine)']), verbo([has]), complemento([been, prepared, and, characterised])]). relacion([sujeto(['The', complex, undergoes, significant, 'oxygen-dependent', quenching, of, emission, with, a, 43, -, fold, reduction, in, luminescence, intensity, between, degassed, and, aerated, acetonitrile, 'solutions,', indicating, its, potential, to]), verbo([act]), complemento([as, a, singlet, oxygen, sensitiser])]). relacion([sujeto(['Fucoidans', are, marine, sulfated, 'polysaccharides,', which]), verbo([act]), complemento([as, glycosaminoglycans, mimetics])]). relacion([sujeto(['We', hypothesized, that, the, size, and, sulfation, rate, of, fucoidans, influence, their, ability, to]), verbo([induce]), complemento(['pro-angiogenic', processes, independently, of, 'GAGs'])]). relacion([sujeto(['The', high, affinities, of, fractionated, fucoidans, to, heparin]), verbo([binding]), complemento([proteins, were, confirmed, by, 'Surface', 'Plasmon', 'Resonance'])]). relacion([sujeto(['We', evidenced, that, 'LMWF']), verbo([has]), complemento([a, higher, 'pro-angiogenic', '(', 2, 'D-angiogenesis', on, 'Matrigel)', and, 'pro-migratory', '(', 'Boyden', 'chamber)', potential, on, 'HUVECs,', compared, to, 'MMWF'])]). relacion([sujeto(['In', 'conclusion,', a, better, characterization, of, the, relationships, between, the, fucoidan, structure, and, its, 'pro-angiogenic', potential, in, 'GAG-free', endothelial, cells, was]), verbo([required]), complemento([to, identify, an, adapted, fucoidan, to, enhance, vascular, repair, in, ischemia])]). relacion([sujeto(['A', diverse, physician, workforce, is, needed, to]), verbo([increase]), complemento([access, to, care, for, underserved, 'populations,', particularly, as, the, 'Affordable', 'Care', 'Act', expands, insurance, coverage])]). relacion([sujeto(['We']), verbo([found]), complemento([that, socioeconomic, and, 'under-represented', minority, disparities, in, admissions, could, be, eliminated, while, maintaining, academic, readiness])]). relacion([sujeto(['Adjusting', applicant, academic, metrics, using, socioeconomic, information, on, medical, school, applications, may, be, a, 'race-neutral', means, of]), verbo([increasing]), complemento([the, socioeconomic, and, 'racial/ethnic', diversity, of, the, physician, workforce])]). relacion([sujeto(['The', 'narrators\'', conclusions, about, the, meaning, of, 'VSED', also, 'vary,', some, perceiving, it, to, be, an, irrational]), verbo([act]), complemento([of, 'suicide,', others, describing, it, as, an, affirmation, of, personal, 'autonomy,', and, most, with, a, mixture, of, sometimes, conflicting, reactions, in, between, these, edges])]). relacion([sujeto(['If', something, belongs, to, someone, 'else,', you, do, not]), verbo([have]), complemento([a, right, to, it])]). relacion([sujeto(['Key', 'quorum-sensing', plaque, bacteria, such, as, 'Fusobacterium', nucleatum]), verbo([act]), complemento([as, bridging, species, between, early, and, late, colonizer, pathogens, such, as, 'Porphyromonas', gingivalis, as, the, biofilm, ages, and, periodontal, inflammation, increases])]). relacion([sujeto(['Pro-inflammatory', cytokine]), verbo([release]), complemento([was, determined, after, 2, ',', 6, ',', and, 24, hours, of, culture, in, the, 'presence/absence', of, different, 'F'])]). relacion([sujeto([nucleatum, significantly]), verbo([increased]), complemento([the, phagocytic, capacity, of, neutrophils])]). relacion([sujeto([nucleatum, strains]), verbo([stimulated]), complemento([a, significant, increase, in, neutrophil, apoptosis, compared, to, the, control, '(', 'p<0'])]). relacion([sujeto([1, ')', and, significantly]), verbo([increased]), complemento([the, expression, of, 'NF-κB', mRNA, in, neutrophils, '(', 'p<0'])]). relacion([sujeto(['Levels', of, 'IL-8', and, 'TNF-α', produced, by, neutrophils, were, significantly]), verbo([increased]), complemento([in, all, 'F'])]). relacion([sujeto(['These', findings]), verbo([suggest]), complemento([that, different, strains, of, 'F'])]). relacion([sujeto(['Two', of, three, subspecies, blocked, neutrophil, superoxide, generation, in, response, to, a, secondary, stimulus]), verbo([preventing]), complemento([oxidative, killing, by, the, neutrophils])]). relacion([sujeto(['We', sought, to, explore, the, relationship, between, the, podiatric, medical, student, and, the, patient, as, it, relates, to, the]), verbo([act]), complemento([of, 'gift-giving', as, a, sign, of, gratefulness, for, the, services, provided])]). relacion([sujeto(['The', relationship, between, the, podiatric, medical, student, and, the, patient, and, the]), verbo([act]), complemento([of, 'gift-giving', by, patients, are, of, ethical, concern])]). relacion([sujeto(['Part', 1, :, 'Importance,', variability, and, 'ratios")', describes, the, current, knowledge, on, the, major, biological, particles, present, in, the, air, regarding, their, global, 'distribution,', 'concentrations,', ratios, and, influence, of, meteorological, factors, in, an, attempt, to]), verbo([provide]), complemento([a, framework, for, monitoring, their, biodiversity, and, variability, in, such, a, singular, environment, as, the, atmosphere])]). relacion([sujeto(['Some', of, them, can]), verbo([cause]), complemento([allergy, and, severe, diseases, in, 'humans,', other, animals, and, 'plants,', with, the, subsequent, economic, impact])]). relacion([sujeto(['Despite', the, harsh, 'conditions,', they, can, be]), verbo([found]), complemento([from, land, and, sea, surfaces, to, beyond, the, troposphere, and, have, been, proposed, to, play, a, role, also, in, weather, conditions, and, climate, change, by, acting, as, nucleation, particles, and, inducing, water, vapour, condensation])]). relacion([sujeto(['In', regards, to, their, global, 'distribution,', marine, environments]), verbo([act]), complemento([mostly, as, a, source, for, bacteria, while, continents, additionally, provide, fungal, and, pollen, elements])]). relacion([sujeto(['Temporal', variability]), verbo([has]), complemento([been, observed, for, all, these, 'organisms,', mostly, triggered, by, global, changes, in, 'temperature,', relative, 'humidity,', et, cetera])]). relacion([sujeto(['We', hypothesized, that, childhood, adversity, predicts, midlife, suicidal, ideation, and, this, is, partially]), verbo([mediated]), complemento([by, adolescent, internalizing, 'disorders,', externalizing, disorders, and, adult, exposure, to, life, events, and, interpersonal, difficulties])]). relacion([sujeto(['At', 45, 'years,', 9377, women, and, men, from, the, 'UK', 1958, 'British', 'Birth', 'Cohort', 'Study']), verbo([participated]), complemento([in, a, clinical, survey])]). relacion([sujeto(['Illness', in, the, 'household,', paternal, 'absence,', institutional, 'care,', parental, divorce, and, retrospective]), verbo([reports]), complemento([of, parental, physical, and, sexual, abuse, predicted, suicidal, ideation, at, 45, years])]). relacion([sujeto(['Three', or, more, childhood, adversities, were]), verbo([associated]), complemento([with, suicidal, ideation, at, 45, years, '[', odds, ratio, '(', 'OR)', 4.31, ',', 95, '%', confidence, interval, '(', 'CI)', 2.67, -, 6.94, ']'])]). relacion([sujeto(['Psychological', distress, at, 16, years, partially]), verbo([mediated]), complemento([the, associations, of, physical, abuse, '(', 'OR', 3.41, ',', 95, '%', 'CI', 2.29, -, 5.75, ')', ',', sexual, abuse, '(', 'OR', 4.99, ',', 95, '%', 'CI', 2.9, -, 11.16, ')', with, suicidal, ideation])]). relacion([sujeto(['Adult', life, events, partially]), verbo([mediated]), complemento([the, association, of, parental, divorce, '(', 'OR', 6.34, ',', 95, '%', 'CI', -, 7.16, to, 36.75, ')', and, physical, '(', 'OR', 9.59, ',', 95, '%', 'CI', 4.97, -, 27.88, ')', and, sexual, abuse, '(', 'OR', 6.59, ',', 95, '%', 'CI', 2.4, -, 38.36, ')', with, suicidal, ideation, at, 45, years])]). relacion([sujeto(['Adversity', in, childhood, predicts, suicidal, ideation, in, 'midlife,', partially]), verbo([mediated]), complemento([by, adolescent, internalizing, and, externalizing, 'disorders,', adult, life, events, and, interpersonal, difficulties])]). relacion([sujeto(['Understanding', the, pathways, from, adversity, to, suicidal, ideation, can, inform, suicide, prevention, and, the]), verbo([targeting]), complemento([of, preventive, interventions])]). relacion([sujeto(['Porcine', cumulus, cells, are, localized, around, oocytes, and]), verbo([act]), complemento([as, a, specific, type, of, granulosa, that, plays, essential, roles, in, the, development, and, maturation, of, 'oocytes,', the, development, and, atresia, of, 'follicles,', and, the, development, of, embryos])]). relacion([sujeto(['Studies', of, 'FAT1']), verbo([have]), complemento([demonstrated, its, functions, in, 'cell-cell', 'contact,', actin, 'dynamics,', and, cell, growth, suppression])]). relacion([sujeto(['The', lack, of, 'FAT1', resulted, in, stable, expression, of, 'CTNNB,']), verbo([enhanced]), complemento([expression, of, cleaved, 'CASP3,', but, decreased, the, 'BCL2/BAX', ratios, at, both, the, mRNA, and, protein, levels])]). relacion([sujeto(['These', results, indicated, that, 'FAT1']), verbo([inhibited]), complemento([porcine, cumulus, cell, apoptosis, via, different, pathways])]). relacion([sujeto(['Taken', 'together,', these, data]), verbo([provide]), complemento([new, insights, into, the, mechanisms, of, the, association, between, 'FAT1', and, porcine, cumulus, cell, apoptosis])]). relacion([sujeto(['Although', considerable, work]), verbo([has]), complemento([addressed, issues, of, 'non-disclosure', from, the, 'client\'s', 'perspective,', there, is, a, lack, of, qualitative, research, into, how, genetic, counselors, address, this, issue, in, practice])]). relacion([sujeto(['The', findings]), verbo([provide]), complemento([indicative, evidence, of, genetic, counselors, employing, a, relational, approach, in, three, escalating, 'stages--covert,', overt, and, 'authoritative--to', encourage, the, disclosure, of, genetic, information])]). relacion([sujeto(['Three', more, groups, of, six, specimens, were, 'created,', and, mineral, trioxide, aggregate, '(', 'MTA),', 'TDM,', and, 'TCP', were, inserted, into, the, perforations, to]), verbo([act]), complemento([as, controls])]). relacion([sujeto(['The', negative, control, group, was]), verbo([associated]), complemento([with, severe, inflammation, and, granulation, tissue, formation])]). relacion([sujeto(['The', specimens, in, the, 'SC+TDM', group, were]), verbo([associated]), complemento([with, significantly, more, bone, formation, than, other, groups, '(', 'P < 0'])]). relacion([sujeto(['SC+TDM', was]), verbo([associated]), complemento([with, significantly, more, bone, formation, when, used, to, repair, uninfected, furcation, perforations, in, the, premolar, teeth, of, dogs])]). relacion([sujeto(['A', 'ultra-high', performance, liquid, 'chromatography-tandem', mass, spectrometry, '(', 'UHPLC-MS/MS)', method, was, established, for, simultaneous, quantification, of, four, caseins, and, two, major, whey, proteins, by, detecting, their, signature, 'peptides,', which, were, able, to]), verbo([act]), complemento([as, markers, for, differentiating, goat, or, sheep, from, cow, whey, and, whole, milk, powder, in, infant, formulas])]). relacion([sujeto(['The', limits, of, quantification, were, 0.01, -, 0.05, &, 'nbsp;g/100 g', for]), verbo([target]), complemento([proteins])]). relacion([sujeto(['Diabetic', macular, edema, '(', 'DME)', can]), verbo([cause]), complemento([blindness, in, diabetic, patients, suffering, from, diabetic, retinopathy, '(', 'DR)'])]). relacion([sujeto(['DM', parameters, controls, '(', 'glycemia,', arterial, 'tension,', and, 'lipids)', are, the, gold, standard, for]), verbo([preventing]), complemento(['DR', and, 'DME'])]). relacion([sujeto(['Although', the, vascular, endothelial, growth, factor, '(', 'VEGF)', is, known, to, play, a, role, in, the, development, of, 'DME,', the, pathological, processes]), verbo([leading]), complemento([to, the, onset, of, this, disease, are, highly, complex, and, the, exact, sequence, in, which, they, occur, is, still, not, completely, understood])]). relacion([sujeto(['Angiogenesis', and, inflammation]), verbo([have]), complemento([been, shown, to, be, involved, in, the, pathogenesis, of, this, disease])]). relacion([sujeto(['However,', it, still, remains, to, be, clarified, whether, angiogenesis, following, 'VEGF', overexpression, is, a]), verbo([cause]), complemento([or, a, consequence, of, inflammation])]). relacion([sujeto(['This', paper]), verbo([provides]), complemento([a, review, of, the, data, currently, 'available,', focusing, on, 'VEGF,', 'angiogenesis,', and, inflammation])]). relacion([sujeto(['Our', analysis]), verbo([suggests]), complemento([that, angiogenesis, and, inflammation, act, interdependently, during, the, development, of, 'DME'])]). relacion([sujeto(['The', concept, of, field, cancerization]), verbo([has]), complemento([frequently, been, quoted, to, explain, the, occurrence, of, multiple, primary, cancers, in, the, head, and, neck, region, and, recurrence, following, complete, excision, of, the, original, tumor])]). relacion([sujeto(['CK', may, be, useful, in, predicting, epithelial, differentiation, and, 'Ki-67', and, p53]), verbo([act]), complemento([as, weak, indicators, of, malignant, disease, progression, in, oral, tissues])]). relacion([sujeto(['Bone', marrow, adipocytes]), verbo([act]), complemento([as, local, regulators, of, skeletal, biology, and, 'homeostasis,', with, recent, studies, suggesting, that, marrow, adipose, tissue, is, metabolically, 'active,', and, can, function, as, an, endocrine, organ])]). relacion([sujeto(['As', 'such,', bone, marrow, adipocytes]), verbo([have]), complemento([the, potential, to, interact, with, tumour, 'cells,', influencing, both, tumour, growth, and, bone, disease])]). relacion([sujeto(['This', review, discusses, the, current, evidence, for, the, role, of, bone, marrow, adipocytes, in, tumour, growth, within, the, bone, marrow, microenvironment, and, the, development, of, the]), verbo([associated]), complemento([bone, disease])]). relacion([sujeto(['The', polyphenol, nordihydroguaiaretic, acid, '(', 'NDGA)']), verbo([has]), complemento([antineoplastic, 'properties,', hence, it, is, critical, to, understand, its, action, at, the, molecular, level])]). relacion([sujeto(['Here,', we, establish, that, 'NDGA']), verbo([inhibits]), complemento([glucose, uptake, and, cell, viability, in, leukemic, 'HL-60', and, 'U-937', cell, lines])]). relacion([sujeto(['We', monitored, hexose, uptake, using, 'radio-labeled', 2, -, deoxyglucose, '(', 2, 'DG)', and]), verbo([found]), complemento([that, the, inhibition, by, 'NDGA', followed, a, noncompetitive, mechanism])]). relacion([sujeto(['In', 'addition,', 'NDGA', blocked, hexose, transport, in, human, red, blood, cells, and, displaced, prebound, cytochalasin, 'B', from, erythrocyte, 'ghosts,']), verbo([suggesting]), complemento([a, direct, interaction, with, the, glucose, transporter, 'GLUT1'])]). relacion([sujeto(['Our', study, shows, for, the, first, time, that, 'NDGA', can]), verbo([act]), complemento([as, inhibitor, of, the, glucose, transporter, 'GLUT1'])]). relacion([sujeto(['Plants']), verbo([respond]), complemento([to, neighbor, shade, by, increasing, stem, and, petiole, elongation])]). relacion([sujeto(['Shade,', sensed, by, phytochrome, 'photoreceptors,']), verbo([causes]), complemento([stabilization, of, 'PHYTOCHROME', 'INTERACTING', 'FACTOR', proteins, and, subsequent, induction, of, 'YUCCA', auxin, biosynthetic, genes])]). relacion([sujeto(['To', investigate, the, role, of, 'YUCCA', genes, in, 'phytochrome-mediated', 'elongation,', we, examined, auxin, signaling, kinetics, after, an, 'end-of-day', 'far-red', '(', 'EOD-FR)', light, 'treatment,', and]), verbo([found]), complemento([that, an, auxin, responsive, reporter, is, rapidly, induced, within, 2, hours, of, 'far-red', exposure])]). relacion([sujeto(['YUCCA2,', 5, ',', 8, ',', and, 9, are, all]), verbo([induced]), complemento([with, similar, kinetics, suggesting, that, they, could, act, redundantly, to, control, 'shade-mediated', elongation])]). relacion([sujeto(['To', test, this, hypothesis, we, constructed, a, 'yucca2,', 5, ',', 8, ',', 9, quadruple, mutant, and]), verbo([found]), complemento([that, the, hypocotyl, and, petiole, 'EOD-FR', and, shade, avoidance, responses, are, completely, disrupted])]). relacion([sujeto(['The', aim, of, this, study, was, to, evaluate, the, soil, and, climatic, variables, that, could, be, closely]), verbo([associated]), complemento([with, the, distribution, of, 'P'])]). relacion([sujeto(['Ten', earthworm, species, '(', 5, 'Neotropical,', 4, 'Palearctic', and, 1, 'Nearctic)', were]), verbo([found]), complemento([along, the, 'gradient,', belonging, to, three, families, '(', 'Rhinodrilidae,', 'Megascolecide', and, 'Lumbricidae)'])]). relacion([sujeto(['Our', results]), verbo([reveal]), complemento([that, soil, fertility, determines, the, abundance, of, earthworms, and, site, '(', 'climate)', can, act, as, a, barrier, to, their, migration])]). relacion([sujeto(['Rapid', reviews, expedite, the, knowledge, synthesis, process, with, the, goal, of]), verbo([providing]), complemento([timely, information, to, healthcare, 'decision-makers', who, want, to, use, 'evidence-informed', policy, and, practice, approaches])]). relacion([sujeto(['A', range, of, opinions, and, viewpoints, on, rapid, reviews, is, thought, to, 'exist;', 'however,', no, research, to, date]), verbo([has]), complemento([formally, captured, these, views])]). relacion([sujeto(['Factor', 'B']), verbo([maintains]), complemento([that, rapid, reviews, should, be, the, exception, and, not, the, rule])]). relacion([sujeto(['The', three, factors, described, offer, insight, into, how, and, why, various, stakeholders]), verbo([act]), complemento([as, they, do, and, what, issues, may, need, to, be, resolved, before, increase, uptake, of, the, evidence, from, rapid, reviews, can, be, realized, in, healthcare, 'decision-making', environments])]). relacion([sujeto(['Mountains', of, the, 'Brazilian', 'Atlantic', 'Forest', can]), verbo([act]), complemento([as, islands, of, cold, and, wet, 'climate,', leading, to, the, isolation, and, speciation, of, species, with, low, dispersal, 'capacity,', such, as, the, toadlet, species, of, the, genus, 'Brachycephalus'])]). relacion([sujeto(['When', the, 'Serra', do, 'Mar', is, subdivided, into, three, 'subunits,', 'Northern,', 'Central', and, 'Southern', 'Serra', do, 'Mar,', the, number, of, species]), verbo([increase]), complemento([from, north, to, the, 'south,', with, records, of, 'six,', 'nine,', and, 16, 'species,', respectively])]). relacion([sujeto(['Brachycephalus', species, are, present, from]), verbo([sea]), complemento([level, to, roughly, 1, ',', 900, m, a])]). relacion([sujeto([',', with, the, highest, richness, being]), verbo([found]), complemento([between, 751, and, 1, ',', 0, m, a])]). relacion([sujeto(['The', altitudinal, occurrence, in, the, pernixspecies, group, seems, to]), verbo([decrease]), complemento([southward])]). relacion([sujeto(['Their', hard, skeletons, form, the, substratum, of, reef, ecosystems, and]), verbo([confer]), complemento([on, corals, their, remarkable, diversity, of, shapes])]). relacion([sujeto(['One', pivotal, question, is, whether, scleractinians, are, a, monophyletic, 'group,', paraphyly, being, an, alternative, possibility, if, corallimorpharians, are, corals, that]), verbo([have]), complemento([lost, their, ability, to, 'calcify,', as, is, implied, by, the, &, 'quot;naked-coral"', hypothesis])]). relacion([sujeto(['Although', the, complete, mitochondrial, genomes, of, a, range, of, scleractinians, and, corallimorpharians]), verbo([have]), complemento([been, 'obtained,', heterogeneity, in, composition, and, evolutionary, rates, means, that, mitochondrial, sequences, are, insufficient, to, understand, the, relationship, between, these, two, groups])]). relacion([sujeto(['These', were, used, in, combination, with, sequences, available, for, a, representative, range, of, scleractinians, to, identify, 291, orthologous, single, copy, 'protein-coding']), verbo([nuclear]), complemento([markers])]). relacion([sujeto(['Unlike', the, mitochondrial, 'sequences,', these]), verbo([nuclear]), complemento([markers, do, not, display, any, distinct, compositional, bias, in, their, nucleotide, or, 'amino-acid', sequences])]). relacion([sujeto(['A', range, of, phylogenomic, approaches, congruently]), verbo([reveal]), complemento([a, topology, consistent, with, scleractinian, monophyly, and, corallimorpharians, as, the, sister, clade, of, scleractinians])]). relacion([sujeto(['It']), verbo([has]), complemento([long, been, suggested, that, 'climate,', especially, atmospheric, pressure, 'change,', can, cause, health, problems, ranging, from, migraine, to, myocardial, infarction])]). relacion([sujeto(['Here,', 'I', hypothesize, that, the, sensory, system, of, epidermal, keratinocytes]), verbo([mediates]), complemento([the, influence, of, atmospheric, pressure, change, on, the, human, physiological, condition])]). relacion([sujeto(['We', previously, demonstrated, that, even, subtle, changes, of, atmospheric, pressure, '(', 5, -, 20, &, 'nbsp;hPa)']), verbo([induce]), complemento([elevation, of, intracellular, calcium, level, in, cultured, human, keratinocytes, '(', excitation, of, 'keratinocytes)'])]). relacion([sujeto(['Moreover,', various, neurotransmitters, and, hormones, that, influence, multiple, systems, '(', 'nervous,', 'cardiovascular,', 'endocrine,', and, immune, 'systems)', are, generated, and]), verbo([released]), complemento([from, epidermal, keratinocytes, in, response, to, various, external, stimuli])]). relacion([sujeto(['Thus,', 'I']), verbo([suggest]), complemento([that, pathophysiological, phenomena, induced, by, atmospheric, pressure, changes, might, be, triggered, by, epidermal, keratinocytes])]). relacion([sujeto(['Triple-negative', breast, 'cancers(TNBCs)are']), verbo([associated]), complemento([with, early, recurrence, after, surgery, and, unfavorable, prognoses])]). relacion([sujeto(['To', 'date,', no, effective, therapies, for, 'TNBCs']), verbo([have]), complemento([been, established])]). relacion([sujeto(['Furthermore,', it]), verbo([suggested]), complemento([that, the, addition, of, further, iv, 'ACTs', to, 'UFT', could, improve, the, outcome, in, patients, with, 'Stage', 'II-III', 'TNBCs'])]). relacion([sujeto(['The', cyclic, electron, flow, around, photosystem, 'I', '(', 'CEF-PSI)']), verbo([increases]), complemento(['ATP/NADPH', production, in, the, 'chloroplast,', acting, as, an, energy, balance, mechanism])]). relacion([sujeto(['Higher', export, of, reducing, power, from, the, chloroplast, in, 'CEF-PSI', mutants]), verbo([has]), complemento([been, correlated, with, higher, mitochondrial, alternative, oxidase, '(', 'AOX)', capacity, and, protein, amount, under, 'high-light', '(', 'HL)', conditions])]). relacion([sujeto(['However,', in, vivo, measurements, of, 'AOX', activity, are, still]), verbo([required]), complemento([to, confirm, the, exact, role, of, 'AOX', in, dissipating, the, excess, of, reductant, power, from, the, chloroplast])]). relacion([sujeto([νalt, was, not]), verbo([increased]), complemento([in, 'CEF-PSI', 'mutants,', while, 'AOX', capacity, was, positively, correlated, with, 'photoinhibition,', probably, due, to, a, reactive, oxygen, 'species-induced', increase, of, 'AOX', protein])]). relacion([sujeto(['The', severe, metabolic, impairment, observed, in, 'CEF-PSI', 'mutants,', as, indicated, by, the]), verbo([increase]), complemento([in, photoinhibition, and, changes, in, the, levels, of, 'stress-related', 'metabolites,', can, explain, their, lack, of, νalt, induction])]). relacion([sujeto(['Correlations', with, metabolite, changes]), verbo([suggest]), complemento([that, νcyt, is, coordinated, with, sugar, metabolism, and, 'stress-related', amino, acid, synthesis])]). relacion([sujeto(['Furthermore,', changes, in, 'glycine-serine', and, 'NADH-NAD(+)', ratios, were, highly, correlated, to, νcyt, 'Taken', 'together,', our, results]), verbo([suggest]), complemento([that, νcyt, can, act, as, a, sink, for, the, excess, of, electrons, from, the, 'chloroplast,', probably, via, photorespiratory, glycine, 'oxidation,', thus, improving, photosynthetic, performance, when, νalt, is, not, induced, under, severe, 'HL', stress])]). relacion([sujeto(['Their', biological, activity, may, result, from, induction, of, oxidative, 'stress,']), verbo([caused]), complemento([by, redox, cycling, or, direct, interaction, with, cellular, 'macromolecules,', in, which, quinones, act, as, electrophiles])]). relacion([sujeto(['The', redox, homeostasis, is, known, as, one, of, factors]), verbo([involved]), complemento([in, 'auxin-mediated', plant, growth, regulation])]). relacion([sujeto(['It', was]), verbo([found]), complemento([that, lawsone, was, much, more, effective, than, juglone, in, increasing, both, 'H2O2', production, and, the, activity, of, antioxidative, enzymes, '(', 'SOD,', 'POX', and, 'CAT)', in, coleoptile, 'cells,', regardless, of, the, presence, of, 'IAA'])]). relacion([sujeto(['An']), verbo([increase]), complemento([in, the, activity, of, 'Cu/Zn-SOD', isoenzymes, induced, by, both, naphthoquinones, suggests, that, 'juglone-', and, 'lawsone-generated', 'H2O2', was, primarily, produced, in, the, cytosolic, and, cell, wall, spaces])]). relacion([sujeto(['The', cell, potential, to, neutralize, hydrogen, 'peroxide,', determined, by, 'POX', and, 'CAT', 'activity,', pointed, to, activity, of, catalase, as, the, main, enzymatic, mechanism, responsible, for, degradation, of, 'H2O2', 'Therefore,', we, assumed, that, generation, of, 'H2O2,']), verbo([induced]), complemento([more, efficiently, by, 'LW', than, 'JG,', was, the, major, factor, accounting, for, differences, in, the, toxicity, of, naphthoquinones, in, maize, coleoptiles])]). relacion([sujeto(['Moreover,', the, results]), verbo([suggested]), complemento([that, oxidative, stress, imposed, by, 'JG', and, 'LW', was, one, of, mechanisms, of, allelopathic, action, of, the, studied, quinones, in, plants])]). relacion([sujeto(['Reducing', methane, emissions, from, ruminants, is, needed, to]), verbo([ensure]), complemento([sustainable, animal, production, in, the, future])]). relacion([sujeto(['Our', findings, show, that, the, rumen, microbiome, in, 'LMY', animals, supports, a, rapid, heterofermentative, 'growth,']), verbo([leading]), complemento([to, lactate, production])]). relacion([sujeto(['Mesenchymal', stem, cells, '(', 'MSCs),', residents, of, the, bone, marrow, and, metastatic, 'niches,', potentially]), verbo([interact]), complemento([with, cancer, cells, 'and/or', their, derived, exosomes])]). relacion([sujeto(['In', this, 'study,', we, investigated, whether, exosomes, derived, from, adult, 'T-cell', 'leukemia/lymphoma', '(', 'ATL)', cells]), verbo([act]), complemento([as, intercellular, messengers, delivering, 'leukemia-related', genes, that, modulate, the, properties, of, human, 'MSCs', in, favor, of, leukemia])]). relacion([sujeto(['We', showed, that, both, 'ATL', cells, '(', 'C81', and, 'HuT-102)', and, 'patient-derived', cells]), verbo([released]), complemento(['Tax-containing', exosomes])]). relacion([sujeto(['We', demonstrated, that, 'HuT-102-derived', exosomes, not, only, deliver, 'Tax', to, recipient, 'MSCs,', but, also]), verbo([induce]), complemento(['NF-κB', activation, leading, to, a, change, in, cellular, 'morphology,', increase, in, proliferation, and, the, induction, of, gene, expression, of, migration, and, angiogenic, markers])]). relacion([sujeto(['These', findings, highlight, the, contribution, of, 'leukemia-derived', exosomes, in, cellular, transformation, and, their, potential, value, as, biomarkers, and]), verbo([targets]), complemento([in, therapeutic, strategies])]). relacion([sujeto(['In a']), verbo([modular]), complemento(['concept,', the, students, shall, learn, important, radiological, core, principles, in, the, realms, of, 'knowledge,', skills, and, competences, as, well, as, core, scientific, competences, in, the, imaging, sciences])]). relacion([sujeto(['Conclusion:', 'The', curriculum, is, meant, as, a, living, document, to, be, amended, and, revised, at]), verbo([regular]), complemento([intervals])]). relacion([sujeto(['•', ' The', 'German', 'Society', of, 'Radiology', '(', 'DRG)', developed, a, model, curriculum, for, teaching, radiology, at, 'German', 'Medical', 'Faculties', to, help, students, develop, the, ability, to, make, medical, decisions, based, on, scientific, knowledge, and]), verbo([act]), complemento([accordingly])]). relacion([sujeto(['We']), verbo([found]), complemento([that, expansion, of, the, 'LN', vasculature, relied, on, the, sequential, assembly, of, endothelial, cell, proliferative, units])]). relacion([sujeto(['This', segmented, growth, was, sustained, by, the, clonal, proliferation, of, high, endothelial, venule, '(', 'HEV)', 'cells,', which]), verbo([act]), complemento([as, local, progenitors, to, create, capillaries, and, 'HEV', 'neo-vessels', at, the, periphery, of, the, 'LN'])]). relacion([sujeto(['Tuberous', sclerosis, complex, '(', 'TSC)', is, a, neurodevelopmental, disease]), verbo([caused]), complemento([by, 'TSC1', or, 'TSC2', mutations, and, subsequent, activation, of, the, mTORC1, kinase])]). relacion([sujeto(['Upon', mTORC1, 'activation,', anabolic, 'metabolism,', which]), verbo([requires]), complemento(['mitochondria,', is, 'induced,', yet, at, the, same, time, the, principal, pathway, for, mitochondrial, 'turnover,', 'autophagy,', is, compromised])]). relacion([sujeto(['We']), verbo([find]), complemento([that, 'Tsc1/2-deficient', neurons, accumulate, mitochondria, in, cell, 'bodies,', but, are, depleted, of, axonal, 'mitochondria,', including, those, supporting, presynaptic, sites])]). relacion([sujeto(['Axonal', and, global, mitophagy, of, damaged, mitochondria, is, 'impaired,']), verbo([suggesting]), complemento([that, decreased, turnover, may, act, upstream, of, impaired, mitochondrial, metabolism])]). relacion([sujeto(['Importantly,', blocking, mTORC1, or]), verbo([inducing]), complemento(['mTOR-independent', autophagy, restores, mitochondrial, homeostasis])]). relacion([sujeto(['Our', study, clarifies, the, complex, relationship, between, the, 'TSC-mTORC1', 'pathway,', 'autophagy,', and, 'mitophagy,', and, defines, mitochondrial, homeostasis, as, a, therapeutic]), verbo([target]), complemento([for, 'TSC', and, related, diseases])]). relacion([sujeto(['Ocular', mucous, membrane, pemphigoid, '(', 'OcMMP)', is, a, rare, autoimmune, disorder, resulting, in, progressive, conjunctival, fibrosis, and, ocular, surface, failure]), verbo([leading]), complemento([to, sight, loss, in, up, to, 50, '%'])]). relacion([sujeto(['This', study, was, designed, to, optimize, an, ocular, surface, sampling, technique, for, identification, of, novel, biomarkers]), verbo([associated]), complemento([with, disease, activity, 'and/or', progressive, fibrosis])]). relacion([sujeto(['At', 12, months, 'follow-up,', 53, '%', of, 'OcMMP', eyes, 'progressed,', and, this, was]), verbo([associated]), complemento([with, baseline, conjunctival, neutrophilia, '(', 'P', =, 0.004, ')'])]). relacion([sujeto(['Notably,', eyes, with, no, visible, inflammation, and, raised, conjunctival, neutrophils, were, more, likely, to, progress, and]), verbo([have]), complemento([a, greater, degree, of, conjunctival, shrinkage, compared, to, those, without, raised, neutrophils])]). relacion([sujeto(['These', data]), verbo([suggest]), complemento([that, 'OSIC-flow', cytometric, analyses, may, facilitate, repeated, patient, sampling])]). relacion([sujeto(['Neutrophils', may]), verbo([act]), complemento([as, a, biomarker, for, monitoring, disease, 'activity,', progressive, 'fibrosis,', and, response, to, therapy, in, 'OcMMP', even, when, the, eye, appears, clinically, uninflamed])]). relacion([sujeto(['Trauma', is, the]), verbo([leading]), complemento([cause, of, death, and, disability, among, young, 'adults,', who, are, also, among, the, most, likely, to, be, uninsured])]). relacion([sujeto(['Efforts', to]), verbo([increase]), complemento([insurance, 'coverage,', including, passage, of, the, 'Patient', 'Protection', and, 'Affordable', 'Care', 'Act', '(', 'ACA),', were, intended, to, improve, access, to, care, and, promote, improvements, in, outcomes])]). relacion([sujeto(['However,', despite]), verbo([reported]), complemento([gains, in, 'coverage,', the, 'ACA\'s', success, in, promoting, use, of, 'high-quality', care, and, enacting, changes, in, clinical, end, points, remains, unclear])]). relacion([sujeto(['To', assess, for, observed, changes, in, insurance, coverage, and, rehabilitation, use, among, young, adult, trauma, patients]), verbo([associated]), complemento([with, the, 'ACA,', including, the, 'Dependent', 'Coverage', 'Provision', '(', 'DCP)', and, 'Medicaid', 'expansion/open', 'enrollment,', and, to, consider, possible, insurance, and, rehabilitation, differences, between, 'DCP-eligible', vs, -, ineligible, patients, and, among, stratified, demographic, and, community, subgroups])]). relacion([sujeto(['The', change, was, primarily, driven, by, 'Medicaid', 'expansion/open', 'enrollment,', which, corresponded, to, a, 20.1, 'percentage-point']), verbo([increase]), complemento([in, 'Medicaid', '(', 95, '%', 'CI,', 18.9, -, 21.3, ')', and, an, 18.2, 'percentage-point', decrease, in, uninsured, '(', 95, '%', 'CI,', -, 19.3, to, -, 17.2, ')'])]). relacion([sujeto(['Rehabilitation', use]), verbo([increased]), complemento([by, 5.4, percentage, points, '(', 95, '%', 'CI,', 4.5, -, 6.2, ')', -, a, 60, '%', relative, increase, from, a, baseline, of, 9, '%'])]). relacion([sujeto(['The', theory, focuses, on, five, moral, 'foundations,', including, 'compassion,', 'fairness,', 'purity,', 'authority,', and, ingroup, 'loyalty;', these]), verbo([have]), complemento([been, found, to, differ, between, liberals, and, conservatives, as, well, as, 'Democrats', and, 'Republicans'])]). relacion([sujeto(['Here', we, 'show,', based, on, the, 'Cornell', 'National', 'Social', 'Survey', '(', 'USA),', that, valuations, of, compassion, and, fairness, were, 'strong,', positive, predictors, of, willingness, to]), verbo([act]), complemento([on, climate, 'change,', whereas, purity, had, a, 'non-significant', tendency, in, the, positive, direction, '(', p, =, 0.07, ')'])]). relacion([sujeto(['As', in, previous, 'studies,', participants, who, were, 'younger,', more, 'liberal,', and]), verbo([reported]), complemento([greater, belief, in, climate, 'change,', also, showed, increased, willingness, to, act, on, climate, change])]). relacion([sujeto(['Our', research, supports, the, potential, importance, of, moral, foundations, as, drivers, of, intentions, with, respect, to, climate, change, 'action,', and]), verbo([suggests]), complemento([that, 'compassion,', 'fairness,', and, to, a, lesser, 'extent,', 'purity,', are, potential, moral, pathways, for, personal, action, on, climate, change, in, the, 'USA'])]). relacion([sujeto(['Neuromedin', 'S', '(', 'NMS),', a, 36, -, amino, acid, 'neuropeptide,']), verbo([has]), complemento([been, found, to, be, involved, in, the, regulation, of, the, endocrine, activity])]). relacion([sujeto(['It']), verbo([has]), complemento([been, also, detected, in, immune, tissues, in, 'mammals,', what, suggests, that, 'NMS', may, play, an, important, role, in, the, regulation, of, immune, response])]). relacion([sujeto(['In', the, present, 'study,', the, results, of, 'RT-PCR', and, western, blot, analysis, revealed, that, 'NMU1R', mRNA, and, protein, were, both]), verbo([expressed]), complemento([in, pig, 'SPLs', and, 'PAMs,', and, the, immunocytochemical, investigations, further, revealed, that, the, positive, signal, of, 'NMU1R', immunoreactivity, was, observed, in, plasma, membranes, of, both, 'SPLs', and, 'PAMs'])]). relacion([sujeto(['In', the, in, vitro, 'study,', we]), verbo([found]), complemento([that, at, concentrations, of, 0.001, -, 1000, nM, 'NMS', alone, or, combined, with, lipopolysaccharide, or, phytohemagglutinin, significantly, increased, 'SPL', proliferation])]). relacion([sujeto(['Application', of, 'ELISA', method, showed, that, 'NMS', could]), verbo([induce]), complemento([the, secretion, of, the, 'pro-inflammatory', cytokines, 'IL-1β,', 'IL-6', and, 'TNF-α', in, 'PAMs'])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, 'NMS', can, act, as, a, potently, positive, 'pro-inflammatory', factor, and, immunomodulatory, agent, that, affects, the, immune, response, of, immune, cells, by, combining, with, its, receptor, 'NMU1R'])]). relacion([sujeto(['Highly']), verbo([conserved]), complemento([eukaryotic, histones, are, polybasic, proteins, that, package, 'DNA', into, 'nucleosomes,', a, building, block, of, 'chromatin,', allowing, extremely, long, 'DNA', molecules, to, form, compact, and, discrete, chromosomes])]). relacion([sujeto(['The', histone, 'N-terminal', tails, that, extend, from, the, nucleosome, core]), verbo([act]), complemento([as, docking, sites, for, many, proteins, through, diverse, 'post-translational', 'modifications,', regulating, various, 'DNA', transactions])]). relacion([sujeto(['In', this, 'report,', we, present, evidence, that, the, nucleosomes, can, positively]), verbo([regulate]), complemento([the, enzymatic, activity, of, 'Rad27', '(', yeast, 'Fen1),', a, major, processing, enzyme, important, for, 'Okazaki', fragment, in, eukaryotes])]). relacion([sujeto(['We']), verbo([found]), complemento([that, individual, 'histones,', histone, 'octamers,', and, nucleosomes, are, able, to, stimulate, 'Rad27', in, a, manner, dependent, on, the, 'N-terminal', tails, of, histones])]). relacion([sujeto(['Kinetic', analyses]), verbo([suggest]), complemento([that, an, increase, in, catalytic, efficiency, of, 'Rad27', was, mainly, due, to, increased, affinity, between, 'DNA', substrates, and, 'Rad27'])]). relacion([sujeto(['It', appears, that, the, physical, interaction, in, vivo, between, histones, and, 'Rad27', results, in, the, enrichment, of, 'Rad27', in, the, vicinity, of, 'chromatin,']), verbo([increasing]), complemento([the, availability, of, 'Rad27', for, various, 'DNA', metabolisms])]). relacion([sujeto(['These', results, indicate, that, nucleosomes, are, not, a, mere, structural, component, of, 'chromatin,', but, an, active, regulator, of, 'DNA', metabolisms, that, serves, to]), verbo([ensure]), complemento([the, efficient, and, faithful, processing, of, structural, intermediates, arising, during, 'DNA', transactions])]). relacion([sujeto(['The', most, commonly]), verbo([reported]), complemento(['PA', types, were, 'walking,', 'cycling,', swimming, and, fitness])]). relacion([sujeto(['The', most, commonly]), verbo([reported]), complemento(['SB', were, 'reading,', 'TV', 'viewing,', and, computer, use])]). relacion([sujeto(['Furthermore,', participants, were, not, aware, of, the, negative, health, effects, of, 'SB', and, not, motivated, to]), verbo([decrease]), complemento([their, 'SB'])]). relacion([sujeto(['Concerning', new, 'PA', 'interventions,', very, diverse, ideas, were, put, 'forward,', reflecting, the, diversity, of, the]), verbo([target]), complemento([group])]). relacion([sujeto(['It', seems, that, a, dynamic, intervention, in, which, participants, can, choose, which, 'PA', type, they, want, to]), verbo([increase]), complemento([is, preferable, for, recently, retired, adults])]). relacion([sujeto(['The', potent, antistaphylococcal, activity, of, 'N-substituted', pantothenamides, '(', 'PanAms)']), verbo([has]), complemento([been, shown, to, at, least, partially, be, due, to, the, inhibition, of, 'Staphylococcus', 'aureus\'s', atypical, type, 'II', pantothenate, kinase, '(', 'SaPanKII),', the, first, enzyme, of, coenzyme, 'A', biosynthesis])]). relacion([sujeto(['This', mechanism, of, action, follows, from, 'SaPanKII', having, a]), verbo([binding]), complemento([mode, for, 'PanAms', that, is, distinct, from, those, of, other, 'PanKs'])]). relacion([sujeto(['The', cocrystal, structures, showed, that, all, of, the, 'PanAms', are]), verbo([phosphorylated]), complemento([by, 'SaPanKII', but, remain, bound, at, the, active, 'site;', this, occurs, primarily, through, interactions, with, 'Tyr240\'', and, 'Thr172\''])]). relacion([sujeto(['Kinetic', analysis, showed, a, strong, correlation, between, kcat, '(', slow, 'PanAm', 'turnover)', and, 'IC50', '(', inhibition, of, pantothenate, 'phosphorylation)', 'values,']), verbo([suggesting]), complemento([that, 'SaPanKII', inhibition, occurs, via, a, delay, in, product, release])]). relacion([sujeto(['Taken', 'together,', our, results, are, consistent, with, an, inhibition, mechanism, wherein, 'PanAms']), verbo([act]), complemento([as, 'SaPanKII', substrates, that, remain, bound, upon, phosphorylation])]). relacion([sujeto(['The', application, of, heat]), verbo([causes]), complemento([the, entire, gel, to, 'shrink,', while, the, application, of, light, causes, the, regions, around, the, functionalized, fibers, to, collapse])]). relacion([sujeto(['In', this, 'configuration,', the, fibers, could]), verbo([act]), complemento([as, grippers, that, bind, objects, in, the, presence, of, light])]). relacion([sujeto(['With', the, illumination, turned, 'off,', the, grippers, could, controllably]), verbo([release]), complemento([the, objects])]). relacion([sujeto(['By', placing, the, fibers, closer, to, the, edge, of, the, 'sample,', the, combination, of, heat, and, light, could, be, harnessed, to]), verbo([bind]), complemento([and, release, larger, objects])]). relacion([sujeto(['Overall,', our, findings]), verbo([provide]), complemento([guidelines, for, controllably, reconfiguring, the, shape, of, soft, materials, and, 'thus,', tailoring, the, material, to, display, different, functionalities, in, different, environments])]). relacion([sujeto(['The', monoamines, octopamine, '(', 'OA)', and, tyramine, '(', 'TA)']), verbo([modulate]), complemento([numerous, behaviours, and, physiological, processes, in, invertebrates])]). relacion([sujeto(['In', 'addition,', these, animals]), verbo([have]), complemento([increased, body, fat, 'deposits,', reduced, physical, activity, and, a, reduced, metabolic, resting, rate])]). relacion([sujeto(['Increasing', the]), verbo([release]), complemento([of, 'OA', from, internal, stores, induced, the, opposite, effects])]). relacion([sujeto(['Flies', devoid, of, both, 'OA', and, 'TA', had, normal, body, fat, and, metabolic, 'rates,']), verbo([suggesting]), complemento([that, 'OA', and, 'TA', act, antagonistically])]). relacion([sujeto(['Moreover,', 'OA-deficient', flies, show]), verbo([increased]), complemento([insulin, release, rates])]). relacion([sujeto(['We', inferred, that, the, 'OA-mediated', control, of, insulin]), verbo([release]), complemento([accounts, for, a, substantial, proportion, of, the, alterations, observed, in, these, flies])]). relacion([sujeto(['Moreover,', chronic, deregulation, of, the, corresponding, signalling, systems, in, humans, may, be]), verbo([associated]), complemento([with, metabolic, 'disorders,', such, as, obesity, or, diabetes])]). relacion([sujeto(['By', comparing, the, simulated, hole, mobility, in, 'PDIB', and, 'PDIB-2OPh,', it, is]), verbo([found]), complemento([that, the, phenoxy, rings, act, as, spacers, between, adjacent, stacking, columns, in, the, 'phenoxy-substituted', derivatives])]). relacion([sujeto(['The', increasement, of, the, number, of, benzene, oxygen, groups]), verbo([leads]), complemento([to, the, absorption, spectra, 'red-shift', of, these, molecular, systems])]). relacion([sujeto(['The', steric, effect, in, 'PDIB-4OPh', is, expected, to]), verbo([cause]), complemento([space, reversal, and, thus, to, changes, in, the, properties, of, the, molecule])]). relacion([sujeto(['In', this, 'study,', we]), verbo([found]), complemento([the, 'cyclin-dependent', kinase, '(', 'CDK4)', to, act, as, a, cancer, stem, cell, regulator, and, novel, prognostic, marker, in, triple, negative, breast, cancers])]). relacion([sujeto(['We']), verbo([found]), complemento(['CDK4', to, be, highly, expressed, in, these, tumors, and, its, expression, to, correlate, with, poor, overall, and, relapse, free, survival, 'outcomes,', high, tumor, grade, and, poor, prognostic, features, of, triple, negative, breast, cancer, patients])]). relacion([sujeto(['Moreover,', we]), verbo([found]), complemento([that, blocking, 'CDK4', expression, or, kinase, 'activity,', using, a, pharmacological, inhibitor, prevented, breast, cancer, stem, cell, 'self-renewal'])]). relacion([sujeto(['Finally,', blocking, 'CDK4', activity, efficiently, eliminated, both, normal, and, 'chemotherapy-resistant', cancer, cells, in, triple, negative, breast, 'cancers,', highlighting, 'CDK4', as, a, promising, novel, therapeutic]), verbo([target]), complemento([for, these, aggressive, breast, tumors])]). relacion([sujeto(['For', a, patient, with, lupus, anticoagulant, '(', 'LA),']), verbo([activated]), complemento([coagulation, time, '(', 'ACT)', was, measured, with, two, different, types, of, devices, '(', 'HEMOCHRON(®)', 801, and, 'HEMOCHRON(®)', 'Jr)'])]). relacion([sujeto(['The', phospholipid, contained, in, an]), verbo([activating]), complemento([agent, of, the, 'HEMOCHRON(®)', 'Jr', was, suggested, to, have, counteracted, the, effect, of, 'LA'])]). relacion([sujeto(['It', was, indicated, that, the, coagulation, status, for, 'LA-positive', patients, might, be, better, assessed, by, 'ACT', measured, with, phospholipid, in, an]), verbo([activating]), complemento(['agent,', although, careful, interpretation, is, required])]). relacion([sujeto(['Of', the, different, mechanisms, that]), verbo([led]), complemento([to, spread, of, 'resistance,', one, notorious, phenomenon, is, the, generation, of, 'Extended', 'Spectrum', 'β-lactamases', '(', 'ESBLs)', preferably, 'TEM,', 'SHV,', 'OXA', and, 'CTX-M'])]). relacion([sujeto(['Alarming', spread, of, resistance]), verbo([has]), complemento([made, it, as, the, subject, of, concern, for, scientific, consideration, and, research])]). relacion([sujeto(['In', this, 'article,', we, emphasized, the, state, of, knowledge, regarding, imprudent, use, of, antibiotics, that]), verbo([act]), complemento([as, promoters, of, resistance, 'development,', thereby, contributing, to, the, failure, of, available, treatment, regimes])]). relacion([sujeto(['Heart', 'failure,', 'hypertension,', cirrhosis, and, nephritic, syndrome, are, among, conditions, that, alter, volume, and, composition, of, body, fluids, and, are]), verbo([modulated]), complemento([by, diuretics])]). relacion([sujeto(['Natural', products, are, important, source, of, diuretics, and]), verbo([have]), complemento([been, considered, remarkable, alternative, with, greater, effectiveness, and, fewer, side, effects])]). relacion([sujeto(['Despite', the, large, number, of, published, articles, claiming, that, plants, or, 'plant-derived', components, may]), verbo([act]), complemento([as, diuretic, 'agents,', few, studies, have, addressed, the, mechanism, of, action, of, medicinal, plants])]). relacion([sujeto(['Thus,', the, aim, of, this, review, was, to]), verbo([provide]), complemento([an, overview, of, the, current, knowledge, about, the, major, cellular, and, molecular, mechanisms, of, diuretic, plants, 'and/or', their, main, compounds])]). relacion([sujeto(['Anorexia', cancer, cachexia, syndrome, is, prevalent, in, advanced, cancer, 'patients,', which, is, featured, by, 'anorexia,']), verbo([decreased]), complemento([dietary, 'intake,', body, weight, loss, '(', skeletal, muscle, mass, 'loss),', and, unable, to, be, reversed, by, routine, nutritional, support, therapy])]). relacion([sujeto(['Up', to, 'now,', the, main, mechanisms]), verbo([involved]), complemento([in, cancer, cachexia, include, excessive, systemic, 'inflammation,', which, is, represented, by, increased, plasma, levels, of, 'IL-1,', 'IL-6,', 'TNF-alpha,', 'tumor-induced', 'factors,', such, as, 'PIF', and, 'LMF'])]). relacion([sujeto(['These', factors, eventually]), verbo([act]), complemento([on, orexigenic, and, anorexigenic, neurons, located, in, hypothalamus, or, protein, and, lipid, metabolism, of, peripheral, 'tissues,', which, lead, to, 'anorexia,', decreased, dietary, 'intake,', enhanced, basic, metabolism, rate, and, hyper, catabolism])]). relacion([sujeto(['However,', studies, about, drugs, used, to, treat, cachexia, are, always, controversial, or, merely, effective, in]), verbo([stimulating]), complemento([appetite, and, increasing, body, 'weight,though', not, lean, body, mass])]). relacion([sujeto(['The', main]), verbo([target]), complemento([of, pharmaceutical, treatment, is, to, improve, 'appetite,', decrease, systemic, inflammation, and, promote, anabolic, metabolism])]). relacion([sujeto(['Traditional', 'Chinese', medicine, '(', 'TCM)', and, natural, herbal, medicines]), verbo([have]), complemento([been, used, in, the, treatment, of, cancer, for, thousands, of, years, 'worldwide,', particularly, in, 'China'])]). relacion([sujeto(['More', and, more, research, show, that, traditional, 'Hanfang', '(', 'Chinese', 'medicines)and', some, natural, herbs, with, less, side, 'reactions,']), verbo([have]), complemento([the, effects, of, antagonizing, 'pro-inflammatory', 'cytokines,', enhancing, immune, 'system,', inhibiting, protein, 'catabolism,', boosting, the, appetite, and, body, 'weight,', which, maybe, an, promising, treatment, strategy, and, development, tendency, for, anorexia, cancer, cachexia, syndrome])]). relacion([sujeto(['While', patients, with, 'CKD', are, at, a, higher, risk, of, premature, death, due, to, cardiovascular, 'complications,', this]), verbo([increased]), complemento([risk, cannot, be, completely, explained, by, classical, cardiovascular, risk, factors, such, as, 'hypertension,', diabetes, 'mellitus,', and, obesity])]). relacion([sujeto(['Instead,', recent, research]), verbo([suggests]), complemento([that, uremic, toxins, may, play, a, key, role, in, explaining, this, marked, increase, in, cardiovascular, mortality, in, patients, with, 'CKD'])]). relacion([sujeto(['While', 'spermine,', a, 'tetra-amine,']), verbo([has]), complemento([previously, been, hypothesized, to, act, as, an, uremic, 'toxin,', the, following, review, presents, a, summary, of, recent, literature, that, casts, doubt, on, this, assertion])]). relacion([sujeto(['Because', of, its, impact, on, multiple, biological, 'pathways,', heparanase]), verbo([has]), complemento([emerged, as, a, major, regulator, of, 'cancer,', inflammation, and, other, disease, processes])]). relacion([sujeto(['Heparanase', accomplishes, this, by, degrading, heparan, sulfate, which]), verbo([regulates]), complemento([the, abundance, and, location, of, 'heparin-binding', growth, factors, thereby, influencing, multiple, signaling, pathways, that, control, gene, 'expression,', syndecan, shedding, and, cell, behavior])]). relacion([sujeto(['In', 'addition,', heparanase, can]), verbo([act]), complemento([via, nonenzymatic, mechanisms, that, directly, activate, signaling, at, the, cell, surface])]). relacion([sujeto(['This', review, focuses, on, recent, developments, in, the, field, of, heparanase, regulation, of, cancer, and, 'inflammation,', including, the, impact, of, heparanase, on, exosomes, and, 'autophagy,', and, novel, mechanisms, whereby, heparanase]), verbo([regulates]), complemento([tumor, 'metastasis,', angiogenesis, and, chemoresistance])]). relacion([sujeto(['Autophagy', '(', literally, &, 'quot;self-eating")', is, an, evolutionarily]), verbo([conserved]), complemento([degradation, process, where, cytoplasmic, components, are, engulfed, by, vesicles, called, 'autophagosomes,', which, are, then, delivered, to, 'lysosomes,', where, their, contents, are, degraded])]). relacion([sujeto(['The', source, of, membranes, that]), verbo([participate]), complemento([in, the, initial, formation, of, phagophores, is, still, incompletely, understood, and, many, intracellular, structures, have, been, shown, to, act, as, lipid, 'donors,', including, the, endoplasmic, 'reticulum,', 'Golgi,', 'nucleus,', mitochondria, and, the, plasma, membrane])]). relacion([sujeto(['A', new]), verbo([finding]), complemento([was, the, discovery, of, two, distinctive, fascicles, attached, to, the, superior, and, inferior, aspects, of, rib, 2])]). relacion([sujeto(['A', proposed, solution, to, this, problem, is, to, create, a, superradiant, laser, using, an, optical, clock, transition, as, its]), verbo([gain]), complemento([medium])]). relacion([sujeto(['This', laser, would]), verbo([act]), complemento([as, an, active, atomic, clock, and, would, be, highly, immune, to, the, fluctuations, in, reference, cavity, length, that, limit, 'today\'s', best, lasers])]). relacion([sujeto(['Pharmacologic', inhibitors, of, the, 'serine/threonine', kinase, 'Akt,', initially, aimed, at, deranged, oncogenic, pathways, in, 'tumors,']), verbo([have]), complemento([recently, been, shown, to, act, as, immunomodulators, that, markedly, enhance, the, antitumor, properties, of, 'T', cells])]). relacion([sujeto(['Freshwater', turtles, are, of, particular, concern, as, they, appear, to]), verbo([have]), complemento([limited, ability, to, cope, with, environmental, conditions, that, are, hyperosmotic, to, their, body, fluids])]). relacion([sujeto(['We', hypothesized, that, these, turtles, would, be, unable, to]), verbo([maintain]), complemento([homeostasis, in, the, 15, '‰', water, treatment, and, would, suffer, osmotic, loss, of, 'water,', increased, ionic, concentrations, and, a, decrease, in, body, mass])]). relacion([sujeto(['Plasma', ionic, concentrations]), verbo([increased]), complemento([proportionally, more, in, 'E'])]). relacion([sujeto(['Individuals', of, both, species, reduced, feeding, in, 15, '‰', 'water,', indicating, that, behaviour, may]), verbo([provide]), complemento([an, additional, means, for, freshwater, turtles, to, limit, 'ion/solute', influx, when, in, hyperosmotic, environments])]). relacion([sujeto(['Although', we, demonstrate, that, these, turtles]), verbo([have]), complemento([mechanisms, to, survive, temporarily, in, saline, 'waters,', it, is, likely, that, sustained, salinization, of, waterways, will, exceed, their, 'short-', to, 'medium-term', capacity, to, survive, increased, salt, 'levels,', making, salinization, a, potentially, key, threatening, process, for, these, freshwater, reptiles])]). relacion([sujeto(['Estuarine', habitats, are, frequently, used, as, nurseries, by, elasmobranch, species, for, their, protection, and, abundant, 'resources;', 'however,', global, climate, change, is]), verbo([increasing]), complemento([the, frequency, and, severity, of, environmental, challenges, in, these, estuaries, that, may, negatively, affect, elasmobranch, physiology])]). relacion([sujeto(['In', both, 'species,', we, observed, a]), verbo([decrease]), complemento([in, plasma, osmolality, brought, about, by, selective, losses, of, 'NaCl,', urea, and, trimethylamine, 'N-oxide,', as, well, as, decreases, in, 'haemoglobin,', haematocrit, and, routine, oxygen, consumption])]). relacion([sujeto(['Heat-shock', protein, levels, varied, between, species, during, the, 'exposure,', but, we]), verbo([found]), complemento([no, evidence, of, protein, damage, in, any, of, the, tissues, tested])]). relacion([sujeto(['Although', both, species, seemed, to, be, able, to, cope, with, this, level, of, osmotic, 'challenge,', overall, the, school, sharks, exhibited, higher, gill, 'Na(+)/K(+)-ATPase', activity, and, ubiquitin, concentrations, in, routine, and, experimental, 'conditions,', a, larger, 'heat-shock', protein, response, and, a, smaller]), verbo([decrease]), complemento([in, routine, oxygen, consumption, during, the, hyposmotic, 'exposure,', suggesting, that, there, are, 'species-specific', responses, that, could, potentially, affect, their, ability, to, withstand, longer, or, more, severe, changes, in, salinity])]). relacion([sujeto(['Emerging', evidence, from, acoustic, monitoring, of, sharks]), verbo([has]), complemento([indicated, variability, in, the, species, found, in, the, 'Pittwater', 'Estuary', during, hyposmotic, 'events,', and, 'together,', our, data, may, help, to, predict, species, abundance, and, distribution, in, the, face, of, future, global, climate, change])]). relacion([sujeto(['Several', studies]), verbo([have]), complemento([linked, 'teachers\'', personality, characteristics, and, sense, of, efficacy, to, stress])]). relacion([sujeto(['A', total, of, 137, teachers, working, in, 'elementary,', 'middle,', and, high, schools, located, in, 'Seoul,', 'South', 'Korea', were]), verbo([recruited]), complemento([for, the, study])]). relacion([sujeto(['The', results, of, the, present, study, indicate, that, harm, avoidance, might, be]), verbo([associated]), complemento([with, 'stress-proneness,', while, 'persistence,', 'self-directedness,', and, sense, of, efficacy, might, act, as, protective, resources, against, stress, in, 'Korean', teachers])]). relacion([sujeto(['We', differ, in, our, 'genomes,', 'environment,', 'behavior,', disease, 'history,', and, past, and, current, medical, 'treatment-a', complex, catalog, of, differences, that, often]), verbo([leads]), complemento([to, variations, in, the, way, each, of, us, responds, to, a, particular, therapy])]). relacion([sujeto(['Depending', on, the, 'disease,', its, 'mechanisms,', and, the, 'therapy,', virtual, patient, models, can, be, implemented, at, a, fairly, high, level, of, 'abstraction,', with, molecular, models, representing, 'cells,', cell, 'types,', or, organs, relevant, to, the, clinical, 'question,']), verbo([interacting]), complemento([not, only, with, each, other, but, also, the, environment])]). relacion([sujeto(['In', the, 'future,', &, 'quot;virtual', 'patient/in-silico', 'self"', models, may, not, only, become, a, central, element, of, our, health, care, 'system,', reducing, otherwise, unavoidable, mistakes, and, unnecessary, 'costs,', but, also]), verbo([act]), complemento([as, &, 'quot;guardian', 'angels"', accompanying, us, through, life, to, protect, us, against, dangers, and, to, help, us, to, deal, intelligently, with, our, own, health, and, wellness])]). relacion([sujeto(['Team-based', care]), verbo([has]), complemento([been, shown, to, offer, more, comprehensive, benefits, to, patients, when, compared, to, standard, 'physician-based', care, alone, in, clinics, for, chronic, conditions])]). relacion([sujeto(['However,', apart, from, 'grant-funded', multidisciplinary, 'clinics,', there, are, no]), verbo([reports]), complemento([on, the, usage, of, 'same-day', physical, therapy, '(', 'PT)', consults, within, a, daily, outpatient, neuromuscular, disease, '(', 'NMD)', physician, clinic])]). relacion([sujeto(['A', total, of, 46, '(', 75.4, '%', ')', patients]), verbo([have]), complemento([either, never, before, received, 'PT', care, or, never, before, received, 'PT', care, for, their, 'NMD,', 67.4, '%', of, whom, were, male])]). relacion([sujeto(['The', 5, -, year, survival]), verbo([increased]), complemento([from, 18, '%', to, 81, '%'])]). relacion([sujeto(['In', 'summary,', the, 'E2F', score]), verbo([provides]), complemento([valuable, prognostic, information, for, 'Stage', 'I', and, predictive, information, for, 'Stage', 'II', lung, adenocarcinoma, patients, and, should, be, further, explored, as, a, decision, support, tool, for, their, treatment])]). relacion([sujeto(['Fatty', acids, '(', 'FAs)']), verbo([bind]), complemento([to, 'Arg-120', of, 'Eallo', increasing, to, different, 'degrees,', depending, on, the, 'FA,', the, 'Vmax', of, its, 'Ecat', partner])]). relacion([sujeto(['We']), verbo([report]), complemento([here, that, movement, of, helical, residues, 120, -, 122, and, loop, residues, 123, -, 129, of, 'Eallo', underlies, the, allosteric, effects, of, 'FAs', and, allosteric, 'COX-2', 'inhibitors,', including, naproxen, and, flurbiprofen])]). relacion([sujeto(['An', 'S121P', substitution, in, both, 'PGHS-2', monomers, yields, a, variant, '(', 'S121P/S121P', 'PGHS-2)', that]), verbo([has]), complemento([1.7, -, 1.8, times, the, 'Vmax', of, native, 'PGHS-2', and, is, relatively, insensitive, to, activation, by, 'FAs', or, inhibition, by, allosteric, inhibitors])]). relacion([sujeto(['This', is, unlike, the, corresponding, native, 'PGHS-2', variant, and]), verbo([suggests]), complemento([that, 'S121P', substitutions, also, unhinge, the, loop, involving, residues, 123, -, 129])]). relacion([sujeto(['We', conclude, the, 'following:', '(', 'a)', the, region]), verbo([involving]), complemento([residues, 120, -, 129, of, unoccupied, 'Eallo', tonically, inhibits, 'Ecat;', '(', 'b)', binding, of, an, activating, 'FA', '(', e])]). relacion([sujeto(['arachidonic,', 'palmitic,', or, oleic, 'acid)', to, 'Eallo', or, an, 'S121P', substitution, in, 'Eallo', repositions, this, region, to]), verbo([increase]), complemento(['Ecat', 'activity;', and, '(', 'c)', allosteric, 'COX', inhibitors, act, by, preventing, 'FA', binding, to, 'Eallo', and, additionally, by, relocating, 'Eallo', residues, to, inhibit, 'Ecat'])]). relacion([sujeto(['In', this, 'study,', we, strove, to, substantiate, the, ability, of, 'linc-MAF-4', to]), verbo([act]), complemento([as, a, regulator, of, pathogenesis, during, multiple, sclerosis, '(', 'MS)'])]). relacion([sujeto(['We']), verbo([recruited]), complemento([34, patients, who, were, diagnosed, with, 'MS', according, to, the, revised, 'McDonald', 'Criteria'])]). relacion([sujeto(['Expression', of, 'linc-MAF-4']), verbo([increased]), complemento([significantly, in, peripheral, blood, mononuclear, cells, of, patients, with, 'MS', compared, with, those, of, control, participants])]). relacion([sujeto(['In', 'addition,', 'linc-MAF-4']), verbo([regulated]), complemento([encephalitogenic, 'T', helper, '(', 'Th)1', cell, differentiation, in, patients, with, 'MS'])]). relacion([sujeto(['Transfection', of, synthetic, 'linc-MAF-4', into, naive, 'CD4(+)', 'T', cells, facilitated, 'Th1', cell, differentiation, and]), verbo([inhibited]), complemento(['Th2', cell, differentiation, by, directly, inhibiting, 'MAF,', which, is, a, 'Th2', cell, transcription, factor])]). relacion([sujeto(['Linc-MAF-4', also]), verbo([promoted]), complemento([activation, of, 'CD4(+)', 'T', cells, from, patients, with, 'MS'])]). relacion([sujeto(['Our', results]), verbo([suggest]), complemento([that, 'linc-MAF-4', is, involved, in, the, pathogenesis, of, 'MS,', specifically, via, regulation, of, encephalitogenic, 'T', cells])]). relacion([sujeto(['Linc-MAF-4']), verbo([regulates]), complemento(['Th1/Th2', differentiation, and, is, associated, with, the, pathogenesis, of, multiple, sclerosis, by, targeting, 'MAF'])]). relacion([sujeto(['The', skin, and, especially, the, stratum, corneum, '(', 'SC)']), verbo([act]), complemento([as, a, barrier, and, protect, epidermal, cells, and, thus, the, whole, body, against, xenobiotica, of, the, external, environment])]). relacion([sujeto(['Topical', skin, treatment]), verbo([requires]), complemento([an, efficient, drug, delivery, system, '(', 'DDS)'])]). relacion([sujeto(['We', determined, by, 'dual-frequency', electron, paramagnetic, resonance, '(', 'EPR)', how, dexamethasone, '(', 'Dx)', labelled, with, 3, -, 'carboxy-2,2,5,5-tetramethyl-1-pyrrolidinyloxy', '(', 'PCA)', is]), verbo([associated]), complemento([with, the, 'CMS'])]). relacion([sujeto(['Additionally,', the, rotational, correlation, time, of, 'spin-labelled', 'Dx', was, probed, by, continuous, wave, 'EPR', at, ambient, 'temperature,', which]), verbo([provides]), complemento([independent, information, on, the, drug, environment])]). relacion([sujeto(['No', studies, could, be]), verbo([found]), complemento([identifying, the, impact, of, body, core, temperature, or, mean, arterial, pressure, on, 'CAL'])]). relacion([sujeto(['Subjective', factors, such, as, the, 'surgeons\'', own, assessment, of, local, perfusion, and, visibility, of, the, operating, field]), verbo([have]), complemento([not, been, the, subject, of, relevant, studies, for, occurrence, in, patients, with, 'CAL'])]). relacion([sujeto(['It']), verbo([mediates]), complemento([the, degradation, of, unfolded, and, damaged, forms, of, the, 'actin-crosslinker', filamin, through, 'chaperone-assisted', selective, autophagy, '(', 'CASA)'])]). relacion([sujeto(['In', 'addition,', 'BAG3']), verbo([stimulates]), complemento([filamin, transcription, in, order, to, compensate, autophagic, disposal, and, to, maintain, the, actin, cytoskeleton, under, strain])]). relacion([sujeto(['Here', we, demonstrate, that, 'BAG3', coordinates, protein, synthesis, and, autophagy, through, spatial, regulation, of, the, mammalian]), verbo([target]), complemento([of, rapamycin, complex, 1, '(', 'mTORC1)'])]). relacion([sujeto(['Interaction', with, 'BAG3', results, in, a, recruitment, of, 'TSC', complexes, to, actin, stress, 'fibers,', where, the, complexes]), verbo([act]), complemento([on, a, subpopulation, of, 'mTOR-positive', vesicles, associated, with, the, cytoskeleton])]). relacion([sujeto(['At', the, same, 'time,', 'BAG3-mediated', sequestration, of, 'TSC1/TSC2', relieves, mTORC1, inhibition, in, the, remaining, 'cytoplasm,', which]), verbo([stimulates]), complemento([protein, translation])]). relacion([sujeto(['The', spatial, regulation, of, mTORC1, exerted, by, 'BAG3', apparently]), verbo([provides]), complemento([the, basis, for, a, simultaneous, induction, of, autophagy, and, protein, synthesis, to, maintain, the, proteome, under, mechanical, strain])]). relacion([sujeto(['Our', intention, was, to]), verbo([find]), complemento([out, whether, repeated, 'ASE', treatment, for, 14, days, 'may:', 1, ')', induce, 'FosB/ΔFosB', expression, in, the, 'PVN;', 2, ')', activate, selected, 'PVN', neuronal, 'phenotypes,', synthesizing, oxytocin, '(', 'OXY),', vasopressin, '(', 'AVP),', corticoliberin, '(', 'CRH)', or, tyrosine, hydroxylase, '(', 'TH);', and, 3, ')', interfere, with, the, impact, of, 'CMS'])]). relacion([sujeto(['Saline', and, 'ASE', did, not]), verbo([promote]), complemento(['FosB/ΔFosB', expression, in, the, 'PVN'])]). relacion([sujeto(['The', study]), verbo([provides]), complemento([an, 'anatomical/functional', knowledge, about, an, unaccented, nature, of, prolonged, 'ASE', treatment, at, the, level, of, 'PVN', and, excludes, its, positive, or, negative, interplay, with, 'CMS', effect])]). relacion([sujeto(['Data', indicate, that, 'long-lasting', 'ASE', treatment, might, not]), verbo([act]), complemento([as, a, stressor, acting, at, the, 'PVN', level])]). relacion([sujeto(['Taking', medicines, as, intended, is, difficult, for, 'everybody,', but, young, people, going, through, adolescence]), verbo([have]), complemento([greater, problems, than, adults, and, younger, children])]). relacion([sujeto(['It', was, evident, that, young, 'people\'s', 'self-care', was, intrinsically, linked, to, their, attempts, to]), verbo([maintain]), complemento([a, sense, of, individually, and, socially, constructed, definitions, of, normality])]). relacion([sujeto(['The']), verbo([act]), complemento([of, taking, 'medication,', and, the, consequences, '(', positive, or, 'negative)', of, that, 'act,', had, an, impact, both, personally, and, socially])]). relacion([sujeto(['This', includes, an, understanding, of, the, identity, transformations, that, young, people, can, experience, and, how, 'decision-making', may, be, affected, by, their, attempts, to]), verbo([retain]), complemento(['pre-diagnosis', identities, 'and/or', develop, new, social, identities])]). relacion([sujeto(['It', had, been, demonstrated, that, sugars, from, various, plants, can]), verbo([act]), complemento([as, potent, 'agents,', which, induce, apoptosis, of, cancer, cells])]). relacion([sujeto(['We', further, evaluated, the, effect, of, determined, molecular, composition]), verbo([found]), complemento([in, the, selected, fraction, by, using, a, mixture, of, commercially, available, 'substances,', which, were, found, in, the, fraction, and, tested, its, 'pro-apoptotic', effect, on, 'HepG2', cells])]). relacion([sujeto(['Out', of, 93, fractions, obtained, by, 'HPLC', from, the, plant, extract, we]), verbo([found]), complemento(['HPLC', fraction, 10, '(', 10, &, 'nbsp;min', 'elution)', was, the, most, effective])]). relacion([sujeto(['HPLC', fraction, 10]), verbo([triggered]), complemento([apoptosis, of, 'HepG2', within, 3, &, 'nbsp;h', in, the, 0.01, -, 1.0, &, 'nbsp;mg/mL', concentration, range])]). relacion([sujeto(['Furthermore,', a, mixture, of, pure, 'cellobiose,', vitamin, 'C,', 'S', and, 'Se', '(', complex, 'cellobiose/C/S/Se)', had, a, very, similar, capacity, in]), verbo([inducing]), complemento([apoptosis, of, 'HepG2', cells, compared, to, 'HPLC', fraction, 10])]). relacion([sujeto(['Complex', 'cellobiose/C/S/Se', was, capable, of]), verbo([inducing]), complemento(['caspase-3', activity, and, led, to, loss, of, mitochondrial, integrity])]). relacion([sujeto(['The', capacity, of, cellobiose, alone, to]), verbo([induce]), complemento([apoptosis, of, 'HepG2', was, approximately, 1000, -, fold, lower, compared, to, complex, 'cellobiose/C/S/Se'])]). relacion([sujeto(['In', this, study, we, present, the, highly, synergistic, effect, of, a, unique, complex, consisting, of, 'cellobiose,', vitamin, 'C,', sulphur, and, selenium, on]), verbo([triggering]), complemento([the, apoptosis, of, human, hepatocellular, carcinoma, '(', 'HepG2)', cell, line])]). relacion([sujeto(['It', was, 'found,', for, the, first, 'time,', that, exposure, of, the, intestinal, mucosa, to, free, 'HCT', resulted, in, an]), verbo([increased]), complemento([and, abnormal, intestinal, permeability, associated, with, several, injuries, to, the, intestinal, epithelium])]). relacion([sujeto(['Nevertheless,', the, 'HCT', delivery, system, obtained, ameliorated, the, damage, of, the, intestinal, epithelium]), verbo([induced]), complemento([by, 'HCT'])]). relacion([sujeto(['Furthermore,', we]), verbo([found]), complemento([that, the, corresponding, permeability, profiles, for, both, the, free, 'HCT', and, the, 'CS/HCT:βCD', 'NPs', were, exponential, and, 'lineal,', respectively])]). relacion([sujeto(['We', propose, that, the]), verbo([increased]), complemento([intestinal, uptake, and, severe, tissue, injury, of, 'HCT', to, the, intestinal, epithelium, could, be, directly, related, to, possible, effects, of, this, drug, on, the, ionoregulatory, 'Na(+/)K(+)-ATPase', channel])]). relacion([sujeto(['Thus,', it, is, postulated, that, the, 'CS/HCT:βCD', 'NPs', may]), verbo([increase]), complemento([the, gastrointestinal, retention, of, the, 'HCT,', which, would, provide, increased, adherence, to, the, mucus, barrier, that, lines, the, intestinal, 'epithelium;', 'consequently,', this, would, act, as, a, slow, 'HCT', release, delivery, system, and, maintain, lower, drug, levels, of, luminal, gut, in, comparison, with, the, administration, of, free, 'HCT,', leading, to, less, severe, local, injury])]). relacion([sujeto(['The', use, of, abdominal, computed, tomography, '(', 'ACT)', for, nontraumatic, abdominal, pain, in, the, pediatric, emergency, department, is]), verbo([increasing]), complemento([to, a, remarkable, 'extent,', and, every, effort, should, be, made, to, select, patients, who, would, benefit, from, 'ACT'])]). relacion([sujeto(['The', radiology]), verbo([reports]), complemento([were, reviewed, to, determine, 'ACT', diagnoses])]). relacion([sujeto(['SD', is, generally, believed, to, be, the, physiological, substrate, of, migraine, aura, and, is]), verbo([associated]), complemento([with, many, other, brain, pathologies])]). relacion([sujeto(['A', systematic, parameter, study]), verbo([reveals]), complemento([that, glia, can, act, as, both, a, disperser, and, buffer, of, potassium, in, 'SD', propagation])]). relacion([sujeto(['Gut', dysbiosis]), verbo([has]), complemento([been, associated, with, several, clinically, relevant, 'conditions,', including, alterations, of, central, nervous, system, '(', 'CNS)', structure, and, function, development])]). relacion([sujeto(['More', than, 350, articles, were, 'found,', and, only, those, published, in, 'English', and]), verbo([providing]), complemento([data, on, aspects, related, to, neurologic, diseases, were, included, in, the, evaluation])]). relacion([sujeto(['The', data, indicate, that, the, gut, microbiota, influences, 'CNS', development, and, function, and, that, gut, dysbiosis, is]), verbo([associated]), complemento([with, significant, neurological, problems])]). relacion([sujeto(['However,', most, of, these, data]), verbo([have]), complemento([been, collected, in, experimental, animals, and, cannot, be, transferred, to, humans])]). relacion([sujeto(['Both', probiotics, and, prebiotics, can]), verbo([have]), complemento([different, impacts, on, 'CNS', according, to, the, microbial, species, or, oligosaccharides, that, are, administered])]). relacion([sujeto(['In', 'humans,', particularly, in, 'children,', several, factors, may, be, important, in, conditioning, gut, microbiota, 'modifications;', 'unfortunately,', most, of, these, factors]), verbo([act]), complemento([simultaneously])]). relacion([sujeto(['More', efforts, are]), verbo([required]), complemento([to, fully, define, both, the, array, of, complex, behaviors, that, are, influenced, by, the, gut, microbiota, at, the, 'CNS', level, and, the, mechanisms, involved])]). relacion([sujeto(['This', structural, similarity, to, 'E2', enables, phytoestrogens, to]), verbo([cause]), complemento(['(', 'anti)oestrogenic', effects, by, binding, to, the, oestrogen, receptors])]). relacion([sujeto(['Various', beneficial, health, effects]), verbo([have]), complemento([been, ascribed, to, 'phytoestrogens,', such, as, a, lowered, risk, of, menopausal, symptoms, like, hot, flushes, and, 'osteoporosis,', lowered, risks, of, cardiovascular, 'disease,', 'obesity,', metabolic, syndrome, and, type, 2, 'diabetes,', brain, function, 'disorders,', breast, 'cancer,', prostate, 'cancer,', bowel, cancer, and, other, cancers])]). relacion([sujeto(['In', contrast, to, these, beneficial, health, 'claims,', the, '(', 'anti)oestrogenic', properties, of, phytoestrogens]), verbo([have]), complemento([also, raised, concerns, since, they, might, act, as, endocrine, 'disruptors,', indicating, a, potential, to, cause, adverse, health, effects])]). relacion([sujeto(['The', literature, overview, presented, in, this, paper, illustrates, that, several, potential, health, benefits, of, phytoestrogens]), verbo([have]), complemento([been, reported, but, 'that,', given, the, data, on, potential, adverse, health, 'effects,', the, current, evidence, on, these, beneficial, health, effects, is, not, so, obvious, that, they, clearly, outweigh, the, possible, health, risks])]). relacion([sujeto(['A', 'carbon-free', nanocomposite, consisting, of, 'MoO2', nanoparticles, embedded, between, 'MoSe2', 'nanosheets,', named, 'MoO2@MoSe2,']), verbo([has]), complemento([been, synthesized, and, demonstrated, excellent, electrochemical, properties, for, lithium, ion, batteries])]). relacion([sujeto(['In', such, a, 'composite,', 'MoSe2', nanosheets]), verbo([provide]), complemento([a, flexible, substrate, for, 'MoO2', 'nanoparticles;', while, 'MoO2', nanoparticles, act, as, spacers, to, retain, the, desired, active, surface, to, electrolyte, and, also, introduce, metallic, conduction])]). relacion([sujeto(['In', 'addition,', the, heterojunctions, at, the, interface, between, 'MoSe2', and, 'MoO2', introduce, a, 'self-built', electric, field, to]), verbo([promote]), complemento([the, 'lithiation/delithiation', process])]). relacion([sujeto(['As', a, 'result,', such, lamellar, composite]), verbo([has]), complemento([a, long, cycling, stability, with, a, reversible, capacity, of, 520.4, mA, h, 'g(-1)', at, a, current, density, of, 2000, mA, 'g(-1)', after, 400, cycles, and, excellent, rate, 'performance,', which, are, attributed, to, the, synergistic, combination, of, the, two, components, in, nanoscale])]). relacion([sujeto(['Since', epidemiologic, data]), verbo([have]), complemento([highlighted, the, positive, effects, of, metformin, to, reduce, cancer, incidence, and, 'mortality,', many, in, vitro, and, in, vivo, studies, as, well, as, a, large, number, of, clinical, trials, have, been, conducted, in, order, to, study, its, potential])]). relacion([sujeto(['The', many, anticancer, actions, of, metformin]), verbo([lead]), complemento([to, a, cytostatic, effect])]). relacion([sujeto(['First,', by]), verbo([decreasing]), complemento([insulinemia, and, 'glycaemia,', metformin, can, block, the, 'PI3K/MAPK', signalling, pathway, implicated, in, cell, growth])]). relacion([sujeto(['Second,', metformin, can, directly]), verbo([act]), complemento([on, cancer, cells, by, targeting, various, pathways, including, tumour, 'metabolism,', 'inflammation,', angiogenesis, or, cancer, stem, 'cells,', mainly, through, the, activation, of, the, 'AMPK', pathway])]). relacion([sujeto([chemotherapy, or, glycolysis, 'inhibitors)', in, order, to, synergistically]), verbo([reveal]), complemento([its, cytotoxic, action])]). relacion([sujeto(['LKB,', p53, or, 'OCT1)', or, low, glucose, 'availability,', metformin, alone, does]), verbo([have]), complemento([cytotoxic, effects])]). relacion([sujeto(['Thus,', it, is, essential, to, consider, the]), verbo([associated]), complemento([biomarkers, in, order, to, determine, the, potential, of, metformin, in, different, types, of, cancers])]). relacion([sujeto(['We', use, molecular, dynamics, simulations, to, investigate, the, tracer, diffusion, in, a]), verbo([sea]), complemento([of, polymers, with, specific, binding, zones, for, the, tracer])]). relacion([sujeto(['These']), verbo([binding]), complemento([zones, act, as, traps])]). relacion([sujeto([',', when, the, polymers, with, traps, are, frozen, in, space, and, the, volume, fraction, and, the]), verbo([binding]), complemento([strength, of, the, traps, are, moderate])]). relacion([sujeto(['Also', the, long, time, dynamics, becomes, subdiffusive, as, the, number, or, the]), verbo([binding]), complemento([strength, of, the, traps, increases])]). relacion([sujeto(['However,', if, the, polymers, are, mobile, then, the, tracer, dynamics, is, 'Gaussian', but, could, be, normal, or, subdiffusive, depending, on, the, number, and, the]), verbo([binding]), complemento([strength, of, the, traps])]). relacion([sujeto(['In', 'addition,', with]), verbo([increasing]), complemento([binding, strength, and, number, of, polymer, 'traps,', the, probability, of, the, tracer, being, trapped, increases])]). relacion([sujeto(['On', the, other, 'hand,', removing, the]), verbo([binding]), complemento([zones, does, not, result, in, 'trapping,', even, at, comparatively, high, crowding])]). relacion([sujeto(['Our', simulations, also, show, that, the, trapping, probability]), verbo([increases]), complemento([with, the, increasing, size, of, the, tracer, and, for, a, bigger, tracer, with, the, frozen, polymer, background, the, dynamics, is, only, weakly, 'non-Gaussian', but, highly, subdiffusive])]). relacion([sujeto(['Our', observations, are, in, the, same, spirit, as]), verbo([found]), complemento([in, many, recent, experiments, on, tracer, diffusion, in, polymeric, materials, and, question, the, validity, of, using, 'Gaussian', theory, to, describe, diffusion, in, a, crowded, environment, in, general])]). relacion([sujeto(['Our', established, 'interleukin-13', '(', 'IL-13', ')', overexpression, rat, model, of, minimal, 'change-like', nephropathy]), verbo([provided]), complemento([a, platform, to, study, the, molecular, signalling, pathways, in, 'T-helper', 2, '(', 'Th2)', cytokine, associated, minimal, change, nephrotic, syndrome])]). relacion([sujeto(['We', hypothesized, that, 'IL-13', may]), verbo([act]), complemento([directly, on, 'podocytes,', causing, podocyte, foot, process, effacement, and, hence, proteinuria, in, our, rat, model, of, minimal, 'change-like', nephropathy])]). relacion([sujeto(['This', study, aimed, firstly, to, delineate, the, glomerular, &, 'quot;gene', 'signature"']), verbo([associated]), complemento([with, 'IL-13-mediated', dysregulation, of, podocyte, related, 'proteins,', and, subsequently, to, investigate, the, role, of, the, differentially, regulated, genes, in, 'IL-13-mediated', podocyte, injury])]). relacion([sujeto(['Gene', expression, of, 'Vav1', was, shown, to, be, highly, 'up-regulated', in, the, glomeruli, of, 'IL-13', -, overexpressed, rats, and, pathway, analysis, of, the, differentially]), verbo([expressed]), complemento([genes, suggested, a, possible, novel, role, of, 'Vav1', in, podocyte, cytoskeleton, remodelling])]). relacion([sujeto(['However,', positive, staining, for, the]), verbo([phosphorylated]), complemento([form, of, 'Vav1', '(', 'p-Vav1)', was, only, seen, in, 'IL-13', -, overexpressed, rats])]). relacion([sujeto(['This', was]), verbo([associated]), complemento([with, 'Rac1', activation, and, actin, cytoskeleton, 'rearrangement,', which, was, abrogated, in, 'Vav1', 'knock-down', podocytes])]). relacion([sujeto(['In', 'conclusion,', we]), verbo([have]), complemento([demonstrated, the, role, of, 'Vav1-Rac1', pathway, characterised, by, phosphorylation, of, 'Vav1,', activation, of, 'Rac1', and, the, subsequent, actin, cytoskeleton, rearrangement, in, 'IL-13', induced, podocyte, 'injury,', possibly, explaining, the, podocyte, foot, process, effacement, seen, in, our, 'IL-13', overexpression, rat, model])]). relacion([sujeto(['Deregulation', of, 'Wnt', signaling]), verbo([has]), complemento([been, associated, with, several, brain, 'pathologies,', including, 'Alzheimer`s', disease])]). relacion([sujeto(['In', recent, 'years,', it]), verbo([has]), complemento([been, suggested, that, the, 'Wnt', pathway, might, act, as, a, central, integrator, of, metabolic, signals, from, peripheral, organs, to, the, 'brain,', which, would, represent, a, new, role, for, 'Wnt', signaling, in, cell, metabolism])]). relacion([sujeto(['Brain', energy, metabolism, is, important, in, almost, all, neurological, 'disorders,', to, which, a]), verbo([decrease]), complemento([in, the, brain, is, capacity, to, utilize, glucose, has, been, linked])]). relacion([sujeto(['In', the, present, 'study,', we]), verbo([found]), complemento([that, acute, treatment, with, 'Wnt3a', ligand, induced, a, large, increase, in, glucose, 'uptake,', without, changes, in, the, expression, or, localization, of, glucose, transporter, type, 3])]). relacion([sujeto(['In', 'addition,', we, observed, that, 'Wnt3a', treatment]), verbo([increased]), complemento([the, activation, of, the, metabolic, sensor, 'Akt'])]). relacion([sujeto(['Moreover,', we, observed, an]), verbo([increase]), complemento([in, the, activity, of, hexokinase, and, in, the, glycolytic, 'rate,', and, both, processes, were, dependent, on, activation, of, the, 'Akt', pathway])]). relacion([sujeto(['The', effect, of, 'Wnt3a', was, independent, of, both, the, transcription, of, 'Wnt']), verbo([target]), complemento([genes, and, synaptic, effects, of, 'Wnt3a'])]). relacion([sujeto(['Together,', our, results]), verbo([suggest]), complemento([that, 'Wnt', signaling, stimulates, glucose, utilization, in, cortical, neurons, through, glycolysis, to, satisfy, the, high, energy, demand, of, these, cells])]). relacion([sujeto(['In', recent, 'years,', various, intervention, strategies]), verbo([have]), complemento([reduced, malaria, morbidity, and, 'mortality,', but, further, improvements, probably, depend, upon, development, of, a, broadly, protective, vaccine])]). relacion([sujeto(['We', identified, a, population, of, memory, 'CD8(+)', 'T cells', that]), verbo([expressed]), complemento([the, gene, signature, of, 'tissue-resident', memory, 'T', '(', 'Trm)', cells, and, remained, permanently, within, the, 'liver,', where, they, patrolled, the, sinusoids])]). relacion([sujeto(['Exploring', the, requirements, for, liver, 'Trm', cell, 'induction,', we, showed, that, by, combining, dendritic, 'cell-targeted', priming, with, liver, inflammation, and, antigen, recognition, on, 'hepatocytes,', high, frequencies, of, 'Trm', cells, could, be]), verbo([induced]), complemento([and, these, cells, were, essential, for, protection, against, malaria, sporozoite, challenge])]). relacion([sujeto(['Our', study, highlights, the, immune, potential, of, liver, 'Trm', cells, and]), verbo([provides]), complemento([approaches, for, their, selective, 'transfer,', 'expansion,', or, 'depletion,', which, may, be, harnessed, to, control, liver, infections, or, autoimmunity])]). relacion([sujeto(['Microglia', can, aggravate, olfactory, dysfunction, by]), verbo([mediating]), complemento([neuronal, death, in, the, olfactory, bulb, '(', 'OB)', of, a, murine, model, of, 'Niemann-Pick', disease, type, 'C1', '(', 'NPC1),', a, fatal, neurodegenerative, disorder, accompanied, by, lipid, trafficking, defects])]). relacion([sujeto(['Microglia', in, the, 'OB', of, 'NPC1', mice, strongly]), verbo([expressed]), complemento(['CX3C', chemokine, receptor, 1, '(', 'Cx3cr1),', a, specific, receptor, for, the, neural, chemokine, 'C-X3-C', motif, ligand, 1, '(', 'Cx3cl1)'])]). relacion([sujeto(['In', 'addition,', a, high, level, of, 'Cx3cl1', was, detected, in, 'NPC1', 'mouse-derived', 'CSF', due, to]), verbo([enhanced]), complemento([catalytic, activity, of, 'Cathepsin', 'S', '(', 'Ctss),', which, is, responsible, for, 'Cx3cl1', secretion])]). relacion([sujeto(['Notably,', nasal, delivery, of, 'Cx3cl1', neutralizing, antibody, or, 'Ctss', inhibitor, could]), verbo([inhibit]), complemento([the, 'Cx3cl1-Cx3cr1', interaction, and, support, neuronal, survival, through, the, suppression, of, microglial, 'activation,', leading, to, an, improvement, in, the, olfactory, function, in, 'NPC1', mice])]). relacion([sujeto(['Relevant', in, vitro, experiments, revealed, that, intracellular, cholesterol, accumulation, could]), verbo([act]), complemento([as, a, strong, inducer, of, abnormal, 'Ctss', activation, 'and,', in, 'turn,', stimulated, the, 'Cx3cl1-Cx3cr1', axis, in, microglia, via, p38, 'mitogen-activated', protein, kinase, signaling])]). relacion([sujeto(['Our', data, address, the, significance, of, 'Cx3cl1-Cx3cr1', interaction, in, the, development, of, microglial, neurotoxicity, and]), verbo([suggest]), complemento([that, 'Ctss', is, a, key, upstream, regulator])]). relacion([sujeto(['Therefore,', this, study, contributes, to, a, better, understanding, of, the, crosstalk, between, neurons, and, microglia, in, the, development, of, the, neurodegeneration, and]), verbo([provides]), complemento([a, new, perspective, for, the, management, of, olfactory, deficits, and, other, 'microglia-dependent', neuropathies])]). relacion([sujeto(['The', evolution, of, insecticide, resistance, by, crop, pests, and, disease, vectors]), verbo([causes]), complemento([serious, problems, for, agriculture, and, health])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, selection, arising, from, variance, in, mating, and, fertilization, success, can, augment, natural, selection, on, pesticide, 'resistance,', meaning, that, sexual, selection, should, be, considered, when, designing, strategies, to, limit, the, evolution, of, pesticide, resistance])]). relacion([sujeto(['The', 'Cnidium', monnieri, fruits, '(', 'CMF)', were, studied, how, they]), verbo([act]), complemento([on, immune, system, as, a, novel, immunostimulator, against, the, infectious, disease])]). relacion([sujeto(['The', 'CMF', significantly]), verbo([enhanced]), complemento([the, concentrations, of, 'NO', and, 'TNF-α', and, the, phagocytosis, activity, in, macrophages])]). relacion([sujeto(['Treatment', with, 'CMF', significantly]), verbo([stimulated]), complemento([the, phagocytosis, of, peritoneal, macrophages, and, induced, the, immunological, mediator, of, 'serum,', splenocyte, and, peritoneal, macrophages, against, the, 'E'])]). relacion([sujeto(['The', 'host-protective', effects, of, 'CMF', might, be, archived, by, improving, immune, 'response,', and, 'CMF', could]), verbo([act]), complemento([to, prevent, pathogenic, microbial, infections, with, immunomodulation])]). relacion([sujeto(['Cell', adhesion, molecules, belonging, to, the, 'Cadm', 'family,', and, in, particular, 'Cadm3', '(', 'axonal)', and, its, heterophilic]), verbo([binding]), complemento([partner, 'Cadm4', '(', 'Schwann', 'cell),', mediate, these, interactions, along, the, internode])]). relacion([sujeto(['Using']), verbo([targeted]), complemento(['shRNA-mediated', 'knockdown,', we, show, that, the, removal, of, axonal, 'Cadm3', promotes, 'Schwann', cell, myelination, in, the, in, vitro, 'DRG', 'neuron/Schwann', cell, myelinating, system])]). relacion([sujeto(['Axons', of, superior, cervical, ganglion, '(', 'SCG)', 'neurons,', which, do, not, normally, support, the, formation, of, myelin, segments, by, 'Schwann', 'cells,']), verbo([express]), complemento([higher, levels, of, 'Cadm3', compared, to, 'DRG', neurons])]). relacion([sujeto(['Knocking', down, 'Cadm3', in, 'SCG', neurons]), verbo([promotes]), complemento([myelination])]). relacion([sujeto(['While', not, in, direct, 'contradiction,', these, in, vitro, results, shed, lights, on, the, apparent, lack, of, phenotype, that, was]), verbo([reported]), complemento([from, in, vivo, studies, of, 'Cadm3(-/-)', mice])]). relacion([sujeto(['Our', results]), verbo([suggest]), complemento([that, 'Cadm3', may, act, as, a, negative, regulator, of, 'PNS', 'myelination,', potentially, through, the, selective, regulation, of, the, signaling, cascades, activated, in, 'Schwann', cells, by, axonal, 'contact,', and, in, particular, by, type, 'III', 'Nrg-1'])]). relacion([sujeto(['Human', cells, encode, six, topoisomerases, '(', 'TOP1,', 'TOP1mt,', 'TOP2α,', 'TOP2β,', 'TOP3α', and, 'TOP3β),', which]), verbo([act]), complemento([on, a, broad, range, of, 'DNA', and, 'RNA', substrates, at, the, nuclear, and, mitochondrial, genomes])]). relacion([sujeto(['Their', catalytic, 'intermediates,', the, topoisomerase, cleavage, complexes, '(', 'TOPcc),', are, therapeutic]), verbo([targets]), complemento([of, various, anticancer, drugs])]). relacion([sujeto(['TOPcc', can, also, form, on, damaged, 'DNA', during, replication, and, 'transcription,', and, engage, specific, repair, 'pathways,', such, as, those]), verbo([mediated]), complemento([by, 'tyrosyl-DNA', phosphodiesterase, 1, '(', 'TDP1)', and, 'TDP2', and, by, endonucleases, '(', 'MRE11,', 'XPF-ERCC1', and, 'MUS81)'])]). relacion([sujeto(['Here,', we, review, the, roles, of, topoisomerases, in]), verbo([mediating]), complemento([chromatin, 'dynamics,', 'transcription,', 'replication,', 'DNA', damage, repair, and, genomic, 'stability,', and, discuss, how, deregulation, of, topoisomerases, can, cause, neurodegenerative, 'diseases,', immune, disorders, and, cancer])]). relacion([sujeto(['Moreover,', zinc, is, also]), verbo([involved]), complemento([in, cellular, signaling, and, enzymes, inhibition])]). relacion([sujeto(['A', zinc, ion, pool, is]), verbo([maintained]), complemento([by, two, types, of, 'proteins:', '(', 'i)', 'zinc-binding', 'proteins,', which, act, as, a, buffer, and, intracellular, donors, of, zinc, and, '(', 'ii)', zinc, transporters, responsible, for, zinc, fluxes, 'into/from', cells, and, organelles])]). relacion([sujeto(['The']), verbo([decreased]), complemento([serum, zinc, ion, levels, have, been, identified, in, patients, suffering, from, various, cancer, 'diseases,', including, head, and, neck, tumors, and, 'breast,', 'prostate,', 'liver,', and, lung, cancer])]). relacion([sujeto(['On', the, 'contrary,']), verbo([increased]), complemento([zinc, ion, levels, have, been, found, in, breast, cancer, and, other, malignant, tissues])]). relacion([sujeto(['The', aim, of, the, present, work, is, an, overview, of, the, importance, of, zinc, 'ions,', zinc, 'transporters,', and, 'zinc-containing', proteins, in, brain, 'tumors,', which, 'are,', after, 'leukemia,', the, second, most, common, type, of, childhood, cancer, and, the, second]), verbo([leading]), complemento([cause, of, death, in, children, after, accidents])]). relacion([sujeto(['Fibroblast', growth, factor, 9, '(', 'FGF9)']), verbo([has]), complemento([been, suggested, to, act, as, an, antidifferentiation, factor, in, cattle, by, reducing, steroidogenesis, and, increasing, cell, proliferation, in, granulosa, '(', 'GC)', and, theca, '(', 'TC)', cells])]). relacion([sujeto(['Abundance', of, 'FGF9', mRNA]), verbo([increased]), complemento([in, 'medium-sized', follicles, from, early, to, late, growing, phase, of, the, dominant, follicle])]). relacion([sujeto(['In', 'summary,', abundance, of, 'FGF9', mRNA, in, 'GC', and, 'TC']), verbo([increases]), complemento([in, 'medium-sized', follicles, during, development, of, dominant, follicles, and, is, less, in, dominant, 'E2-active', than, subordinate, 'E2-inactive', 'follicles,', suggesting, that, 'FGF9', signaling, could, contribute, to, normal, follicle, development, and, steroidogenesis, in, dairy, cattle])]). relacion([sujeto(['Chemotherapy-induced', peripheral, neuropathy, '(', 'CIPN)', represents, a, serious, complication]), verbo([associated]), complemento([with, antineoplastic, drugs])]). relacion([sujeto(['Although', there, are, no, medications, available, that, effectively]), verbo([prevent]), complemento(['CIPN,', many, classes, of, drugs, have, been, used, to, treat, this, 'condition,', including, 'anticonvulsants,', serotonin, and, noradrenaline, reuptake, 'inhibitors,', and, opioids])]). relacion([sujeto(['In', 'addition,', 'PEA', administered, via, intraplantar, injection, into, a, 'paw,', intrathecal, 'injection,', and, intracerebroventricular, injection, reversed, 'paclitaxel-induced', 'allodynia,']), verbo([suggesting]), complemento([that, it, may, act, at, multiple, sites, in, the, neuroaxis, and, periphery])]). relacion([sujeto(['These', findings, taken, together]), verbo([suggest]), complemento([that, 'PEA', possesses, potential, to, treat, peripheral, neuropathy, in, cancer, patients, undergoing, chemotherapy])]). relacion([sujeto(['As', fast, 'responders,', innate, lymphocytes]), verbo([have]), complemento([protective, or, pathogenic, roles, in, the, initiation, as, well, as, the, maintenance, of, immune, responses, in, 'general,', and, they, contribute, to, tissue, 'homeostasis,', among, other, functions])]). relacion([sujeto(['Innate', lymphocytes, also, seem, to, be]), verbo([involved]), complemento([in, autoimmunity, in, particular])]). relacion([sujeto(['Since', 2010, ',', accumulating, evidence, clearly, shows, that, different, populations, of, innate, lymphocytes]), verbo([have]), complemento([roles, in, responding, to, 'antigen-specific', autoantibody, and, autoreactive, 'T', 'cells,', thereby, amplifying, or, attenuating, disease, processes])]). relacion([sujeto(['Finally,', innate, lymphocytes, can]), verbo([respond]), complemento([to, biologic, therapies, for, autoimmune, diseases])]). relacion([sujeto(['Consequently,', like, 'TNF', and, other, effector, 'molecules,', certain, innate, lymphocyte, subsets, might, be, appropriate, therapeutic]), verbo([targets]), complemento([to, ameliorate, various, autoimmune, diseases])]). relacion([sujeto(['We', also, discuss, how, biologic, therapies, influence, innate, lymphocyte, function, and, consider, the, potential, for, these, cell, subsets, to]), verbo([act]), complemento([as, future, therapeutic, targets])]). relacion([sujeto(['To', develop, functional, 'nanoplatform,', hexalayer, nanofilm, is, precisely, designed, by, 'layer-by-layer', assembly, technique, based, on, electrostatic, interaction, with, four, kinds, of, 'materials:', 'Hydrolyzed', 'poly(β-amino', 'ester)', can, help, cDNA]), verbo([release]), complemento([from, the, film])]). relacion([sujeto(['A', cDNA, is, used, as, a, key, building, block, to]), verbo([activate]), complemento(['DNA', nanodevice])]). relacion([sujeto(['Reduced', graphene, oxides, '(', 'rGOs)', and, the, conductive, polymer]), verbo([provide]), complemento([conductivity])]). relacion([sujeto(['In', 'particular,', rGOs, efficiently, incorporate, a, cDNA, in, the, film, via, several, interactions, and]), verbo([act]), complemento([as, a, barrier])]). relacion([sujeto(['Depending', on, the, types, of, applied, electronic, stimuli, '(', reductive, and, oxidative, 'potentials),', a, cDNA]), verbo([released]), complemento([from, the, electrode, can, quantitatively, control, the, activation, of, 'DNA', nanodevice])]). relacion([sujeto(['From', this, 'report,', a, new, system, is, successfully, demonstrated, to, precisely, control, 'DNA']), verbo([release]), complemento([on, demand])]). relacion([sujeto(['They']), verbo([act]), complemento([as, intercellular, messengers, that, give, the, ability, to, communicate, between, both, cells, of, the, same, type, and, other, cell, types])]). relacion([sujeto(['They', are]), verbo([released]), complemento([by, healthy, 'cells,', both, constitutively, and, upon, cell, activation, and, play, an, important, role, in, immune, system, function])]). relacion([sujeto([are, essential, for, healthy, physiological, 'conditions,', however, under, pathological, 'circumstances,', they]), verbo([act]), complemento([to, potentiate, cellular, stress, and, damage])]). relacion([sujeto(['VPS33B', and, 'VIPAR', comprise, the, two, known, components, of, the, recently, christened, class, 'C', 'Homologues', in, 'Endosome-Vesicle', 'Interaction', '(', 'CHEVI)', 'complex,', thought, to]), verbo([act]), complemento([as, a, tethering, complex, in, endosomal, trafficking, distinct, from, the, 'HOPS', and, 'CORVET', complexes, in, mammalian, cells])]). relacion([sujeto(['A', recent, paper, in, 'The', 'Journal', of, 'Pathology', further, explores, the, role, of, the, 'CHEVI', complex, in, the, biogenesis, of, 'α-granules', in, 'megakaryocytes,', identifying, two, novel, interactors, of, this, 'complex:', 'α-tubulin', and, 'SEC22B,', and, demonstrating, that, 'VPS33B', expression, is]), verbo([required]), complemento([for, the, localization, of, 'SEC22B', and, the, 'α-granule', cargo, 'VWF', to, proplatelets, in, megakaryocytes])]). relacion([sujeto(['Since', abscisic, acid, '(', 'ABA)', can]), verbo([act]), complemento([as, an, important, 'long-distance', 'signal,', we, conducted, a, joint, investigation, of, ontogenetic, and, drought, impacts, on, 'CAM', intensity, and, 'ABA', levels, in, different, leaf, groups, within, the, 'G'])]). relacion([sujeto(['The', drought, treatment, of, 'mature-tank', rosettes, generally]), verbo([induced]), complemento([in, older, leaves, a, more, severe, water, 'loss,', followed, by, the, lowest, 'CAM', activity, and, a, higher, increase, in, 'ABA', 'levels,', while, younger, leaves, showed, an, opposite, response])]). relacion([sujeto([&, 'nbsp;monostachia']), verbo([responded]), complemento([to, drought, with, variable, degrees, of, water, loss, and, 'CAM', expression])]). relacion([sujeto(['ABA', seems, to]), verbo([participate]), complemento([in, this, 'tissue-compartmented', response, as, a, 'long-distance', signalling, 'molecule,', transmitting, the, 'drought-induced', signals, originated, in, older, leaves, towards, the, younger, ones])]). relacion([sujeto(['Hydrogen', sulfide, '(', 'H2', 'S)']), verbo([modulates]), complemento([many, pathophysiological, 'processes,', including, inflammation, and, allergic, 'reactions,', in, which, mast, cells, act, as, major, effector, cells])]). relacion([sujeto(['IgE', receptor, '(', 'FcεRI)', cross, linking]), verbo([leads]), complemento([to, an, increase, in, intracellular, calcium, '(', '[', 'Ca(+2)', ']', i, ')', ',', a, critical, step, in, mast, cell, degranulation])]). relacion([sujeto(['We', investigated, the, effects, of, 'H2', 'S,', either, endogenously, produced, or]), verbo([released]), complemento([by, the, slow, 'H2', 'S', donor, 4, -, 'carboxy-phenyl', isothiocyanate, '(', 'PhNCS-COOH),', on, 'antigenic-', and, 'non-antigenic', degranulation, of, native, murine, mast, 'cells,', and, human, and, rat, '(', 'RBL-2H3)', mast, cell, lines])]). relacion([sujeto(['We', measured, the]), verbo([release]), complemento([of, specific, mast, cell, degranulation, markers, '(', 'β-hexosaminidase', and, 'renin),', as, well, as, changes, in, '[', 'Ca(+2)', ']', i, and, phosphorylation, of, proteins, downstream, of, 'FcεRI', activation])]). relacion([sujeto(['Endogenously', produced, 'H2', 'S']), verbo([inhibited]), complemento(['antigen-induced', degranulation, in, 'RBL-2H3'])]). relacion([sujeto(['Similarly,', 'H2', 'S']), verbo([released]), complemento([by, 'PhNCS-COOH', '(', 10, -, 300, &, 'nbsp;μM)', 'reduced,', in, a, 'concentration-dependent', 'manner,', antigenic, and, 'non-antigenic', degranulation, and, renin, release, in, all, mast, cell, types])]). relacion([sujeto(['Notably,', 'PhNCS-COOH', also]), verbo([prevented]), complemento([in, a, 'concentration-dependent', mode, the, increase, in, '[', 'Ca(+2)', ']', i, elicited, by, 'Ca(+2)', 'ionophore,', thapsigargin, and, 'FcεRI', activation])]). relacion([sujeto(['These', findings]), verbo([suggest]), complemento([that, 'PhNCS-COOH', could, be, a, strategic, therapeutic, tool, in, mast, 'cell-mediated', allergic, conditions])]). relacion([sujeto(['One', type, of, 'autophagy,', 'macroautophagy,', is, a, tightly]), verbo([regulated]), complemento([process, facilitated, by, 'autophagy-related', '(', 'Atg)', proteins, that, must, communicate, effectively, and, act, in, concert, to, enable, the, de, novo, formation, of, the, 'phagophore,', its, maturation, into, an, 'autophagosome,', and, its, subsequent, targeting, and, fusion, with, the, lysosome, or, the, vacuole])]). relacion([sujeto(['Autophagy', plays, a, significant, role, in, 'physiology,', and, its, dysregulation]), verbo([has]), complemento([been, linked, to, several, 'diseases,', which, include, certain, 'cancers,', 'cardiomyopathies,', and, neurodegenerative, diseases])]). relacion([sujeto(['We', also, briefly, highlight, recently, uncovered, molecular, mechanisms, specific, to, neurons, allowing, them, to, uniquely]), verbo([regulate]), complemento([this, catabolic, process, to, accommodate, their, complicated, architecture, and, 'non-dividing', state])]). relacion([sujeto(['Overall,', these, distinct, mechanisms, establish, a, conceptual, framework, addressing, how, macroautophagic, dysfunction, could, result, in, maladies, of, the, nervous, 'system,']), verbo([providing]), complemento([possible, therapeutic, avenues, to, explore, with, a, goal, of, preventing, or, curing, such, diseases])]). relacion([sujeto(['MIF']), verbo([has]), complemento([become, a, promising, drug, target, for, inflammatory, diseases])]). relacion([sujeto(['Apart', from, its, cytokine, 'activities,', 'MIF', is, known, to]), verbo([act]), complemento([as, a, 'd-dopachrome', tautomerase])]). relacion([sujeto(['Our', previous, work]), verbo([has]), complemento([identified, that, 3, -, '[', '(', 'biphenyl-4-ylcarbonyl)carbamothioyl]amino', benzoic, acid, '(', 'Z-590)', exhibited, a, potent, inhibitory, activity, against, 'MIF'])]). relacion([sujeto(['Our', results, demonstrate, that, 'Z-590', significantly]), verbo([decreases]), complemento([the, production, of, nitric, oxide, '(', 'NO),', tumour, necrosis, 'factor-alpha', '(', 'TNF-α),', interleukin, '(', 'IL)-6,', 'IL-1β,', cyclooxygenase, '(', 'COX-2),', inducible, nitric, oxide, synthase, '(', 'iNOS)', as, well, as, reactive, oxygen, species, '(', 'ROS)', involved, in, inhibiting, 'MAKPs', signalling, pathway, in, 'LPS-stimulated', microglia, cells])]). relacion([sujeto(['Furthermore,', 'Z-590', reduced, cytotoxicity, of]), verbo([activated]), complemento([microglia, toward, 'HT-22', hippocampal, cells, in, a, 'microglia-conditioned', medium, system])]). relacion([sujeto(['Atmospheric', carbon, dioxide, '(', 'CO2', ')', directly, determines, the, rate, of, plant, photosynthesis, and, indirectly, effects, plant, productivity, and, fitness, and, may, therefore]), verbo([act]), complemento([as, a, selective, pressure, driving, 'evolution,', but, evidence, to, support, this, contention, is, sparse])]). relacion([sujeto(['Gene', expression, responses, to, elevated, 'CO2', '(', 'acclimation)', were, modest, '[', 33, -, 131, genes, differentially]), verbo([expressed]), complemento(['(', 'DE)],', whilst, those, between, control, and, spring, plants, '(', 'adaptation)', were, considerably, larger, '(', 689, -, 853, 'DE', 'genes)'])]). relacion([sujeto(['In', 'contrast,', population, genomic, analysis, showed, that, genetic, differentiation, between, spring, and, control, plants, was, close, to, 'zero,', with, no, fixed, 'differences,']), verbo([suggesting]), complemento([that, plants, are, adapted, to, their, native, 'CO2', environment, at, the, level, of, gene, expression])]). relacion([sujeto(['An', unusual, phenotype, of]), verbo([increased]), complemento([stomatal, index, in, spring, but, not, control, plants, in, elevated, 'CO2', correlated, with, altered, expression, of, stomatal, patterning, genes, between, spring, and, control, plants, for, three, loci, '(', 'YODA,', 'CDKB1;1', and, 'SCRM2)', and, between, ambient, and, elevated, 'CO2', for, four, loci, '(', 'ER,', 'YODA,', 'MYB88', and, 'BCA1)'])]). relacion([sujeto(['We', propose, that, the, two, positive, regulators, of, stomatal, number, '(', 'SCRM2)', and, 'CDKB1;1', when, upregulated]), verbo([act]), complemento([as, key, controllers, of, stomatal, adaptation, to, elevated, 'CO2'])]). relacion([sujeto(['Combined', with, significant, transcriptome, reprogramming, of, photosynthetic, and, dark, respiration, and]), verbo([enhanced]), complemento([growth, in, spring, 'plants,', we, have, identified, the, potential, basis, of, plant, adaptation, to, high, 'CO2', likely, to, occur, over, coming, decades])]). relacion([sujeto(['Southern', blot, hybridisation, established, that, most, of, them, lacked, the, 'Rht-B1', 'gene,', but]), verbo([retained]), complemento([the, homoeologues, 'Rht-A1', and, 'Rht-D1'])]). relacion([sujeto(['Deletion', of, the, 'B-genome-specific', homoeologues, of, these, two, genes, was, confirmed, in, the, 'Rht-B1', deletion, 'lines,', indicating]), verbo([loss]), complemento([of, more, than, a, single, gene])]). relacion([sujeto(['The', deletions, ranged, from, interstitial, deletions, of, 4, 'BS', through, to]), verbo([loss]), complemento([of, all, 4, 'BS', markers])]). relacion([sujeto(['Cytogenetic', studies, on, selected, lines, confirmed, the]), verbo([loss]), complemento([of, portions, of, 4, 'BS', in, lines, that, lacked, most, or, all, 4, 'BS', markers])]). relacion([sujeto(['These', nested, deletion, lines, share, a, common, genetic, background, and, will]), verbo([have]), complemento([applications, in, assigning, markers, to, regions, of, 4, 'BS', as, well, as, to, 4, 'BL'])]). relacion([sujeto(['Although', the, process, of, biomineralisation]), verbo([has]), complemento([been, reported, in, some, organs, of, 'soybean,', we, now, report, the, description, and, quantification, of, calcium, oxalate, crystals, in, vegetative, and, reproductive, organs, of, soybean, during, its, life, 'cycle,', as, they, act, as, an, important, source, of, calcium, to, the, 'soil,', once, the, harvesting, is, finished])]). relacion([sujeto(['Soybean', produced, prismatic, calcium, oxalate, crystals, in, vegetative, and, reproductive, 'organs,', generally]), verbo([associated]), complemento([with, vascular, 'bundles,', resulting, in, a, potencial, transfer, to, the, soil, of, 81.4, &, 'nbsp;x 10(7)', 'crystals·ha(-1)', throughout, its, life, cycle])]). relacion([sujeto([2, and, 14.5, &, 'nbsp;± 4 μm', in, 'length,', 'respectively),', the, crystal, density]), verbo([increased]), complemento(['(', 293.2, and, 409, 'crystals·mm(-2)', ',', 'respectively)'])]). relacion([sujeto(['These', results, will, contribute, to, knowledge, of, the, amount, of, calcium, oxalate, crystals]), verbo([involved]), complemento([in, the, process, of, 'Ca', recycling, through, cultivated, vegetation, in, fields, from, humid, plains, at, medium, 'latitudes,', which, therefore, have, 'biological,', 'botanical,', biogeochemical, and, pedological, relevance])]). relacion([sujeto(['Thus,', cells, are, constantly, exposed, to, diverse, types, of, genotoxic, insults, that, challenge, genome, 'stability,', including, those, that]), verbo([induce]), complemento([oxidative, 'DNA', damage])]). relacion([sujeto(['In', this, 'study,', we, tested, the, hypothesis, that, chronic, and, repeated, exposure, to, a, micromolar, concentration, of, hydrogen, peroxide, '(', 'H2O2)', could]), verbo([activate]), complemento(['DNA', damage, 'responses,', resulting, in, cellular, adaptations])]). relacion([sujeto(['We']), verbo([report]), complemento([that, intermittent, 'long-term', exposure, to, this, oxidative, stimulus, nearly, eliminated, cell, toxicity, and, significantly, decreased, genotoxicity, '(', in, 'particular,', a, &, 'gt;5-fold', decreased, in, 'double-strand', 'breaks)', resulting, from, subsequent, acute, exposure, to, oxidative, stress])]). relacion([sujeto(['This', protection, was]), verbo([associated]), complemento([with, cell, cycle, arrest, in, 'G2/M', and, induction, of, expression, of, nine, 'DNA', repair, genes])]). relacion([sujeto(['The', 'Dual', 'Visuomotor', 'Channel', theory, of, reaching, proposes, that, a, 'reach-to-grasp']), verbo([act]), complemento([integrates, a, 'Reach,', directed, toward, the, extrinsic, properties, of, the, target, '(', 'location),', and, a, 'Grasp,', directed, toward, the, intrinsic, properties, of, the, target, '(', size, and, 'shape)'])]). relacion([sujeto(['Previous', studies, of, 'reach-to-grasp']), verbo([report]), complemento([that, the, 'Grasp', is, altered, in, pantomime, tasks, made, from, a, starting, position, with, digit, 1, and, digit, 2, closed, and, proximal, to, the, target])]). relacion([sujeto(['Although', being, essential, in, plants, for, 'N', assimilation, and, 'recycling,', kinetic, commitments, and, transition, states, of, the, reaction]), verbo([have]), complemento([not, been, clearly, established, yet])]). relacion([sujeto([965, ')', ',']), verbo([suggesting]), complemento([that, the, reaction, intermediate, is, involved, in, an, 'amidation-deamidation', equilibrium, favoring, '(', 15, ')', 'N'])]). relacion([sujeto([0, ')', ',']), verbo([suggesting]), complemento([that, the, amidation, step, of, the, catalytic, cycle, involves, a, transition, state, with, minimal, alteration, of, overall, force, constants, at, the, 'C-5', carbon])]). relacion([sujeto(['Surprisingly,', the, solvent, isotope, effect, was]), verbo([found]), complemento([to, be, 'inverse,', that, 'is,', with, a, higher, 'turn-over', rate, in, heavy, water, '(', '(', 'D)V ≈ 0'])]). relacion([sujeto(['Several', homodimers, were, taken, into, 'account,', highlighting, the, versatility, of, these, compounds, to]), verbo([act]), complemento([as, both, electron, donors, and, electron, acceptors])]). relacion([sujeto(['Finally,', some, 'X-ray', 'solid-state', structures, retrieved, from, the, 'Cambridge', structural, database, were, described, to, demonstrate, the, importance, of, these, interactions]), verbo([involving]), complemento([boron, derivatives, in, the, solid, state])]). relacion([sujeto(['Recently,', it]), verbo([has]), complemento([been, proposed, that, 'Si', may, act, by, an, interaction, with, this, biometal, in, the, root, apoplast, contributing, to, its, movement, through, the, 'plant,', as, in, the, case, of, 'Fe', deficiency])]). relacion([sujeto(['In', the, present, 'work,', the, effect, of, initial, or, continuous, 'Si', doses, in, soybean, 'Zn', deficient, plants]), verbo([has]), complemento([been, studied])]). relacion([sujeto(['An', initial, addition, of, 0.5, &, 'nbsp;mM', of, 'Si', to, the, nutrient, solution]), verbo([led]), complemento([to, an, enhancement, of, plants, 'growth,', 'Zn', and, 'Si', content, in, 'leaves,', and, a, higher, storage, of, 'Zn', in, the, root, apoplast])]). relacion([sujeto(['The', results]), verbo([suggest]), complemento([that, this, treatment, enhanced, 'Zn', accumulation, on, roots, and, its, movement, to, shoots, when, 'needed,', mitigating, 'Zn', deficiency, symptoms])]). relacion([sujeto(['Jasmonic', acid, '(', 'JA)', signaling, pathway, in, plants, is]), verbo([activated]), complemento([against, various, developmental, processes, as, well, as, biotic, and, abiotic, stresses])]). relacion([sujeto(['The', 'Jasmonate', 'ZIM-domain', '(', 'JAZ)', protein, 'family,', the, key, regulator, of, plant, 'JA', signaling, 'pathway,', also]), verbo([participates]), complemento([in, phytohormone, crosstalk])]). relacion([sujeto(['This', is, the, first, study]), verbo([revealed]), complemento([the, 'in vivo', interactions, of, finger, millet, '(', 'Eleusine', coracana, '(', 'L'])]). relacion([sujeto(['From', the, 'MJ-treated', finger, millet, 'seedlings,', the, 'EcJAZ']), verbo([interacting]), complemento([proteins, were, purified, by, affinity, chromatography, with, the, 'EcJAZ-matrix'])]). relacion([sujeto(['Apart', from, the, previously, identified, 'JAZ']), verbo([binding]), complemento(['proteins,', most, 'prominently,', 'EcJAZ', was, found, to, interact, with, transcription, factors, like, 'NAC,', 'GATA', and, also, with, 'Cold', responsive, protein, '(', 'COR),', etc])]). relacion([sujeto([that, might]), verbo([have]), complemento([extended, the, range, of, functionalities, of, 'JAZ', proteins])]). relacion([sujeto(['Our', results, indicated, that, the, 'EcJAZ', protein, of, finger, millet, could]), verbo([act]), complemento([as, the, signaling, hub, for, the, 'JA', and, other, phytohormone, signaling, 'pathways,', in, response, to, a, diverse, set, of, stressors, and, developmental, cues, to, provide, survival, fitness, to, the, plant])]). relacion([sujeto(['Enhancing', the, flavor, of, fruits, plays, a, fundamental, role, in, improving, fruit, 'quality,', and, volatile, compositions, as, well, as, acid, and, sugar, accumulation, are, significant, factors, that]), verbo([have]), complemento([an, impact, on, the, acceptability, of, sensory, responses, by, human, beings])]). relacion([sujeto(['Vacuoles', in, plants, not, only, function, as, cell, compartments, that, store, amino, 'acids,', sugars, and, other, metabolites, but, also]), verbo([act]), complemento([as, lytic, organelles, where, vacuolar, proteins, are, 'post-translationally', processed, into, mature, forms, or, degraded, by, the, action, of, vacuolar, processing, enzyme, '(', 'VPE)'])]). relacion([sujeto(['We']), verbo([have]), complemento([previously, characterized, 'VPE', genes, '(', 'SlVPE1-5)', during, fruit, development, in, tomato, and, discovered, that, the, 'VPE', enzyme, activity, negatively, interfered, with, sugar, accumulation, in, mature, fruits])]). relacion([sujeto(['Comparative', proteomic, analysis, demonstrated, that, acid, invertase, was, one, of, the, molecular]), verbo([targets]), complemento([of, 'SlVPE5,', which, is, involved, in, the, hydrolysis, of, sucrose])]). relacion([sujeto(['This', study, also, showed, that]), verbo([decreased]), complemento(['VPE', enzyme, activity, due, to, suppression, of, 'SlVPE5', by, 'RNAi', strategy, '(', 'RNAi-SlVPE5)', accompanied, with, decreased, enzyme, activity, of, acid, invertase])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, 'SlVPE5', regulates, 'post-transcriptional', processing, through, de, novo, synthesis, of, the, acid, invertase, protein, to, suppress, enzyme, 'activity,', thereby, eventually, ensuring, sucrose, hydrolysis])]). relacion([sujeto(['We', recently]), verbo([reported]), complemento([that, stressed, adipocytes, release, extracellular, vesicles, '(', 'EVs)', that, act, as, &, 'quot;find-me"', signals, to, promote, macrophage, migration, and, activation])]). relacion([sujeto(['Circulating', 'EVs', were, significantly]), verbo([increased]), complemento([in, mice, with, 'diet-induced', obesity, '(', 'DIO)', and, in, obese, humans, with, metabolic, syndrome, compared, to, lean, controls])]). relacion([sujeto(['This']), verbo([increase]), complemento([was, associated, with, decreased, glucose, tolerance, in, the, 'DIO', mice, and, metabolic, 'dysfunction,', elevated, 'insulin,', and, homeostatic, model, assessment, of, insulin, resistance, '(', 'HOMA-IR)', in, the, obese, humans])]). relacion([sujeto(['In', obese, 'humans,', circulating, levels, of, 'EVs', enriched, in, perilipin, 'A', were, 'dynamic,']), verbo([decreasing]), complemento([35, &, 'nbsp;%', '(', p, &, 'lt;', 0.05, ')', after, a, 3, -, month, reduced, calorie, diet, intervention])]). relacion([sujeto(['This', translational, study]), verbo([provides]), complemento([an, extensive, characterization, of, 'adipocyte-derived', 'EVs'])]). relacion([sujeto(['•', 'Circulating', 'EVs', are, elevated, in, obese, mice, and]), verbo([associated]), complemento([with, glucose, intolerance])]). relacion([sujeto(['•', 'Perilipin', 'A', and, 'EV', levels, are]), verbo([increased]), complemento([in, the, circulation, of, obese, mice, and, human])]). relacion([sujeto(['•', 'Circulating', 'EV', and, perilipin, 'A', levels]), verbo([decrease]), complemento([with, low, calorie, intervention])]). relacion([sujeto(['Long', noncoding, 'RNAs', '(', 'lncRNAs)']), verbo([have]), complemento([been, reported, to, play, pivotal, roles, in, a, variety, of, cancers])]). relacion([sujeto(['However,', lncRNAs]), verbo([involved]), complemento([in, hepatocellular, carcinoma, '(', 'HCC)', initiation, and, progression, remain, largely, unclear])]). relacion([sujeto(['In', this, 'study,', we, identified, an, lncRNA, gradually]), verbo([increased]), complemento([during, hepatocarcinogenesis, '(', 'lncRNA-GIHCG)', using, publicly, available, microarray, data])]). relacion([sujeto(['Functional', experiments, showed, that, 'GIHCG']), verbo([promotes]), complemento(['HCC', cells, 'proliferation,', 'migration,', and, invasion, in, 'vitro,', and, promotes, xenografts, growth, and, metastasis, in, vivo])]). relacion([sujeto(['Mechanistically,', we, demonstrated, that, 'GIHCG', physically]), verbo([associates]), complemento([with, 'EZH2', and, the, promoter, of, 'miR-200b/a/429,', recruits, 'EZH2', and, 'DNMT1', to, the, 'miR-200b/a/429', promoter, 'regions,', upregulates, histone, 'H3K27', trimethylation, and, 'DNA', methylation, levels, on, the, 'miR-200b/a/429', 'promoter,', and, dramatically, silences, 'miR-200b/a/429', expression])]). relacion([sujeto(['Collectively,', our, results, demonstrated, the, roles, and, functional, mechanisms, of, 'GIHCG', in, 'HCC,', and, indicated, 'GIHCG', may]), verbo([act]), complemento([as, a, prognostic, biomarker, and, potential, therapeutic, target, for, 'HCC'])]). relacion([sujeto(['KEY', 'MESSAGE:', 'lncRNA-GIHCG', is, upregulated, in, 'HCC', and]), verbo([associated]), complemento([with, poor, survival, of, patients])]). relacion([sujeto(['GIHCG', significantly]), verbo([promotes]), complemento([tumor, growth, and, metastasis, of, 'HCC'])]). relacion([sujeto(['GIHCG', physically]), verbo([associates]), complemento([with, 'EZH2'])]). relacion([sujeto(['Since', the, discovery, of]), verbo([induced]), complemento([pluripotent, stem, cells, there, has, been, intense, interest, in, understanding, the, mechanisms, that, allow, a, somatic, cell, to, be, reprogrammed, back, to, a, pluripotent, state])]). relacion([sujeto(['Several', groups]), verbo([have]), complemento([studied, the, alterations, in, gene, expression, that, occur, as, somatic, cells, modify, their, genome, to, that, of, an, embryonic, stem, cell])]). relacion([sujeto(['Underpinning', many, of, the, gene, expression, changes, are, modifications, to, the, epigenetic, profile, of, the]), verbo([associated]), complemento([chromatin])]). relacion([sujeto(['We']), verbo([have]), complemento([used, a, 'large-scale', shRNA, screen, to, identify, epigenetic, modifiers, that, act, as, barriers, to, reprogramming])]). relacion([sujeto(['We']), verbo([have]), complemento([uncovered, an, important, role, for, 'TRIM28', in, cells, resisting, transition, between, somatic, and, pluripotent, states])]). relacion([sujeto(['TRIM28', achieves, this, by]), verbo([maintaining]), complemento([the, 'H3K9me3', repressed, state, and, keeping, endogenous, retroviruses, '(', 'ERVs)', silenced])]). relacion([sujeto(['Bacillus', subtilis, effectively]), verbo([inhibited]), complemento(['P'])]). relacion([sujeto(['The', reduction, was, followed, by, those]), verbo([induced]), complemento([by, 'A'])]). relacion([sujeto(['None', of, the, 'cell-free', supernatant, '(', 'CFS)', was, able, to]), verbo([prevent]), complemento([pathogen, growth])]). relacion([sujeto(['Three', antagonists, could]), verbo([suppress]), complemento(['PAT', production, by, 'P'])]). relacion([sujeto(['In', 'addition,', the, three, strains]), verbo([led]), complemento([to, a, 0, '·56-1·47 log CFU g(-1)', reduction, in, colony, number, of, 'P'])]). relacion([sujeto(['The', selected, antagonists, could, be, applied, before, harvesting, to, control, apple, infection, by, 'PAT-producing', fungi, and, also, during, processing, to]), verbo([act]), complemento([as, 'PAT', detoxifiers])]). relacion([sujeto([&, 'nbsp;tumefaciens', to]), verbo([inhibit]), complemento(['P'])]). relacion([sujeto([&, 'nbsp;expansum', is, currently, 'available,', the, results, of, this, study]), verbo([provide]), complemento([some, new, perspectives, to, the, biocontrol, field])]). relacion([sujeto(['Excited-state', intramolecular, proton, transfer, '(', 'ESIPT)', is, a, particularly, well, known, reaction, that]), verbo([has]), complemento([been, very, little, studied, in, magnetic, environments])]). relacion([sujeto(['In', this, 'work,', we]), verbo([report]), complemento([on, the, photophysical, behavior, of, a, known, 'ESIPT', dye, of, the, benzothiazole, 'class,', when, in, solution, with, uncoated, superparamagnetic, iron, oxide, 'nanoparticles,', and, when, grafted, to, 'silica-coated', iron, oxide, nanoparticles])]). relacion([sujeto(['Uncoated', iron, oxide, nanoparticles]), verbo([promoted]), complemento([the, fluorescence, quenching, of, the, 'ESIPT', 'dye,', resulting, from, collisions, during, the, lifetime, of, the, excited, state])]). relacion([sujeto(['The', assembly, of, iron, oxide, nanoparticles, with, a, shell, of, silica]), verbo([provided]), complemento([recovery, of, the, 'ESIPT', 'emission,', due, to, the, isolation, promoted, by, the, silica, shell])]). relacion([sujeto(['The', silica, network, gives, protection, against, the, fluorescence, quenching, of, the, 'dye,', allowing, the, nanoparticles, to]), verbo([act]), complemento([as, a, bimodal, '(', optical, and, 'magnetic)', imaging, contrast, agent, with, a, large, 'Stokes', shift])]). relacion([sujeto(['Experiments', assessing, seed, set, after, single, flower, visits, were, performed, to, determine, whether, thieving, 'short-billed', sunbirds, can]), verbo([act]), complemento([as, substitute, pollinators])]). relacion([sujeto(['Short', billed, sunbirds, are, unable, to]), verbo([act]), complemento([as, substitute, 'pollinators,', and, seed, set, is, significantly, lower, in, the, flowers, that, they, 'visited,', compared, to, flowers, visited, by, 'long-billed', sunbirds])]). relacion([sujeto(['This', is, substantiated, on, a, landscape, 'scale,', where, fruit, production, in, 'Chasmanthe', floribunda, could, artificially, be]), verbo([increased]), complemento([by, 35, '%', in, transformed, 'landscapes,', but, not, so, in, natural, areas])]). relacion([sujeto(['These', findings]), verbo([have]), complemento([important, consequences, for, the, management, and, conservation, of, 'long-tubed', 'bird-pollinated', plant, species, that, exist, in, recently, transformed, landscapes])]). relacion([sujeto(['Although', 'Runx2', is]), verbo([involved]), complemento([in, the, regulation, of, cellular, 'differentiation,', its, physiological, roles, in, the, differentiation, of, uterine, stromal, cells, during, decidualization, still, remain, unknown])]). relacion([sujeto(['The', results, showed, that, 'Runx2', was, highly]), verbo([expressed]), complemento([in, the, decidua, and, 'oil-induced', decidualized, cells])]). relacion([sujeto(['In', the, uterine, stromal, 'cells,', recombinant, human, 'Runx2', '(', 'rRunx2)', could]), verbo([induce]), complemento([the, expression, of, 'Prl8a2', and, 'Prl3c1', which, are, two, 'well-known', differentiation, markers, for, 'decidualization,', while, inhibition, of, 'Runx2', with, specific, siRNA, reduced, their, expression])]). relacion([sujeto(['Further', study]), verbo([found]), complemento([that, rRunx2, could, improve, the, expression, of, 'Prl8a2', and, 'Prl3c1', in, the, 'C/EBPβ', 'siRNA-transfected', stromal, cells])]). relacion([sujeto(['In', the, stromal, 'cells,', cAMP, analogue, 8, -, 'Br-cAMP', could]), verbo([induce]), complemento([the, expression, of, 'Runx2'])]). relacion([sujeto(['Runx2', might]), verbo([act]), complemento([downstream, of, 'C/EBPβ', to, regulate, the, expression, of, 'Cox-2,', 'Vegf', and, 'Mmp9', in, the, uterine, stromal, cells])]). relacion([sujeto(['The', maternal, deficiency, of, vitamin, 'D', can]), verbo([act]), complemento([on, organogenesis, in, mice, 'offspring,', being, a, risk, factor, for, chronic, diseases, in, adulthood])]). relacion([sujeto(['The', maternal, vitamin, 'D-restricted', diet, modifies, the, development, of, the, pancreas, of, the, 'offspring,']), verbo([leading]), complemento([to, islet, remodeling, and, altered, 'insulin-signaling', pathway])]). relacion([sujeto(['The']), verbo([decrease]), complemento([of, 'PDX-1', is, probably, significant, to, the, changes, in, the, 'beta-cell', mass, and, insulin, secretion, in, adulthood])]). relacion([sujeto(['In', forests, of, the, humid, subtropics, of, 'China,', chronically, elevated, nitrogen, '(', 'N)', 'deposition,', predominantly, as, ammonium, '(', 'NH4(+)', ')', ',']), verbo([causes]), complemento([significant, nitrate, '(', 'NO3(-)', ')', leaching, from, 'well-drained', acid, forest, soils, on, hill, slopes, '(', 'HS),', whereas, significant, retention, of, 'NO3(-)', occurs, in, 'near-stream', environments, '(', groundwater, discharge, 'zones,', 'GDZ)'])]). relacion([sujeto(['Our', data, show, that, effective, removal, of, atmogenic, 'NH4(+)', and, production, of, 'NO3(-)', in, soils, on, 'HS', were]), verbo([associated]), complemento([with, a, significant, decrease, in, 'δ(15)', 'N-NO3(-)', ',', suggesting, efficient, nitrification, despite, low, soil, pH])]). relacion([sujeto(['This', decline, was]), verbo([associated]), complemento([with, a, significant, increase, in, both, 'δ(15)', 'N', and, 'δ(18)', 'O', of, residual, 'NO3(-)', ',', providing, evidence, that, the, 'GDZ', acts, as, an, 'N', sink, due, to, denitrification])]). relacion([sujeto(['The', observed, apparent, '(', 15, ')', 'N', enrichment, factor, '(', 'ε)', of, 'NO3(-)', of, about, -, 5, '‰', in, the, 'GDZ', is, similar, to, values, previously]), verbo([reported]), complemento([for, efficient, denitrification, in, riparian, and, groundwater, systems])]). relacion([sujeto(['This', 'study,', explicitly]), verbo([recognizing]), complemento([hydrologically, connected, landscape, 'elements,', reveals, an, overlooked, but, robust, 'N', sink, in, 'N-saturated,', subtropical, forests, with, important, implications, for, regional, 'N', budgets])]). relacion([sujeto(['We', evaluated, the, prevalence, and, factors]), verbo([associated]), complemento([with, 'anxiety,', depression, and, fatigue, at, the, 5, -, year, review, of, a, longitudinal, cohort, study, following, a, first, clinical, diagnosis, of, 'CNS', demyelination, '(', 'FCD)'])]). relacion([sujeto(['Cases', with, a, 'FCD', were]), verbo([recruited]), complemento([soon, after, diagnosis, and, followed, annually, thereafter])]). relacion([sujeto(['Younger', 'age,', higher, 'disability,', concussion, or, other, disease, diagnosis, were, independently]), verbo([associated]), complemento([with, a, higher, anxiety, 'score;', male, 'sex,', higher, 'disability,', being, 'unemployed,', less, physical, 'activity,', and, antidepressant, 'and/or', 'anxiolytic-sedative', medication, use, were, independently, associated, with, a, higher, depression, score])]). relacion([sujeto(['Higher', 'disability,', immunomodulatory, medication, 'use,', other, disease, diagnosis, and, 'anxiolytic-sedative', medication, use, were, independently]), verbo([associated]), complemento([with, having, 'fatigue,', while, female, 'sex,', higher, 'BMI,', having, had, a, 'concussion,', being, unemployed, and, higher, disability, were, associated, with, a, higher, fatigue, score])]). relacion([sujeto(['As', soon, as, a, patient, comes, to, know, that, 'he/she']), verbo([has]), complemento(['cancer,', the, stress, starts, and, psychological, intervention, is, required])]). relacion([sujeto(['Intervention', was]), verbo([required]), complemento([to, measures, include, acceptance, of, the, 'disease,', managing, 'stress,', well, -, 'being,', and, meaning, of, life])]). relacion([sujeto(['This', acceptance, and, commitment, therapy, can, be, an, effective, intervention, approach, for, cancer, patients, that]), verbo([increases]), complemento([acceptance, regarding, disease, and, simultaneously, leads, to, improvement, in, the, meaning, of, life])]). relacion([sujeto(['Here', we, present, an, overview, of, what, is, known, about, endogenous, plant, compounds, that]), verbo([act]), complemento([as, inhibitors, of, hormonal, transport, processes, in, 'plants,', about, their, identity, and, mechanism, of, action])]). relacion([sujeto(['We']), verbo([have]), complemento([also, summarized, commonly, and, less, commonly, used, compounds, of, 'non-plant', origin, and, synthetic, drugs, that, show, at, least, partial, '\'', 'specificity\'', to, transport, or, transporters, of, particular, phytohormones])]). relacion([sujeto(['A', 'randomized,', 'placebo-controlled,', efficacy, trial, of, 'Carraguard', was, unable, to, demonstrate, a, reduction, in, 'women\'s', risk, of, 'HIV', 'infection,', which, may]), verbo([have]), complemento([been, 'due,', in, 'part,', to, low, adherence, '(', gel, used, in, 42, &, 'nbsp;%', of, vaginal, sex, 'acts,', on, 'average)'])]). relacion([sujeto(['A', secondary, analysis, was, undertaken, to, understand, baseline, factors]), verbo([associated]), complemento([with, high, adherence, '(', gel, used, in, '≥85 %', of, sex, 'acts)'])]). relacion([sujeto(['Women', who]), verbo([reported]), complemento(['≥1', vaginal, sex, 'act,', returned, '≥1', opened, 'applicator,', and, had, '≥1', conclusive, 'post-enrollment', 'HIV', test, '(', 'N = 5990)', were, included])]). relacion([sujeto(['Adherence', was, estimated, as, the, ratio, of, average, weekly, applicator, insertions, '(', based, on, a, dye, stain, assay, indicating, vaginal, 'insertion)/average', weekly, sex]), verbo([acts]), complemento(['(', by, 'self-report)'])]). relacion([sujeto(['Women']), verbo([reporting]), complemento([&, 'gt;1', 'and ≤2', vaginal, sex, acts, per, 'week,', on, 'average,', were, half, as, likely, to, be, adherent, as, those, reporting, 1, vaginal, sex, act, per, week, or, 'less [adjusted', odds, ratio, '(', 'AOR):', 0.48, ;, 95, &, 'nbsp;%', 'CI', 0.38, -, 0.61, ']', ;, women, from, the, 'Western', 'Cape had', 'one-third', the, odds, of, being, adherent, compared, to, women, from, 'KZN', '(', 'AOR:', 0.31, ;, 95, &, 'nbsp;%', 'CI', 0.23, -, 0.41, ')', ;, compared, to, women, using, injectable, 'contraception,', women, using, any, other, or, no, method, were, more, likely, to, be, adherent, '(', 'AOR:', 1.3, ;, 95, &, 'nbsp;%', 'CI', 1.04, -, 1.63, ')', ;, and, women, who, had, a, larger, age, gap, from, their, partners, were, more, likely, to, be, adherent, '(', 'AOR:', 1.03, ;, 95, &, 'nbsp;%', 'CI', 1.01, -, 1.05, ;, 'p = 0'])]). relacion([sujeto(['In', 'mammals,', there, are, embryonic, stem, cells, that, generate, germ, 'layers,', and, adult, stem, 'cells,', which]), verbo([act]), complemento([as, a, repair, system, for, the, body, and, maintain, the, normal, turnover, of, regenerative, organs])]). relacion([sujeto(['Their', commitment, and, differentiation, depend, on, several]), verbo([interacting]), complemento([signaling, pathways, and, transcription, factors])]). relacion([sujeto(['Most', 'GNAS-based', disorders]), verbo([have]), complemento([the, common, feature, of, episodic, de, novo, formation, of, islands, of, 'extraskeletal,', qualitatively, 'normal,', bone, in, skin, and, subcutaneous, fat])]). relacion([sujeto(['The', tissue, distribution, of, these, lesions]), verbo([suggests]), complemento([that, pathogenesis, involves, abnormal, differentiation, of, 'MSCs', 'and/or', more, committed, precursor, cells, that, are, present, in, subcutaneous, tissues])]). relacion([sujeto(['Data', coming, from, transgenic, mice, support, the, concept, that, 'GNAS', is, a, key, factor, in, the, regulation, of, lineage, switching, between, osteoblast, and, adipocyte, 'fates,', and, that, its, role, may, be, to]), verbo([prevent]), complemento([bone, formation, in, tissues, where, bone, should, not, form])]). relacion([sujeto(['Despite', the, growing, knowledge, about, the, process, of, heterotopic, ossification, in, rare, genetic, 'disorders,', the, pathophysiological, mechanisms, by, which, alterations, of, cAMP, signaling]), verbo([lead]), complemento([to, ectopic, bone, formation, in, the, context, of, mesenchymal, tissues, is, not, fully, understood])]). relacion([sujeto(['Municipalities']), verbo([have]), complemento([an, overarching, structure, in, health, promotion])]). relacion([sujeto(['In', 'contrast,', quality, management, for, health, promotion, is, not, based, on]), verbo([binding]), complemento([requirements])]). relacion([sujeto([&, 'quot;Regular"', immigrants, such, as, work, migrants, in, 'Germany']), verbo([have]), complemento([the, same, entitlement, to, health, care, coverage, through, the, statutory, health, insurance, as, the, majority, population])]). relacion([sujeto(['Care', provision, is]), verbo([regulated]), complemento([in, different, ways, by, the, 'communities;', it, is, further, complicated, by, different, regulations, at, the, federal, state, levels, and, by, differences, in, knowledge, of, the, physicians, on, how, entitlement, restrictions, can, be, circumvented, on, a, 'case-by-case', basis])]). relacion([sujeto(['Restrictions', on, entitlement, to, health, care, are]), verbo([associated]), complemento([with, higher, health, care, expenditure])]). relacion([sujeto(['They', may, also]), verbo([lead]), complemento([to, delayed, treatment, of, 'life-threatening', conditions])]). relacion([sujeto(['To', assess, 'species\'', vulnerability, to, climate, change, and]), verbo([target]), complemento([ongoing, conservation, 'investments,', researchers, and, managers, often, consider, the, effects, of, projected, changes, in, climate, and, land, use, on, future, habitat, availability, and, quality, and, the, uncertainty, associated, with, these, projections])]). relacion([sujeto(['We', use, an, integrated, set, of, hydrological, and, climatological, projections, that]), verbo([provide]), complemento([physically, based, measures, of, water, balance, under, historical, and, projected, future, climatic, conditions])]). relacion([sujeto(['This', method, isolates, the, impact, of, greenhouse, gas, emissions, and]), verbo([ensures]), complemento([that, modeling, errors, are, incorporated, into, the, baseline, rather, than, attributed, to, climate, change])]). relacion([sujeto(['However,', we]), verbo([found]), complemento([little, evidence, for, a, shift, in, the, locations, expected, to, provide, the, highest, wetland, densities, under, current, vs])]). relacion([sujeto(['We']), verbo([suggest]), complemento([that, targeting, conservation, towards, wetland, complexes, containing, both, small, and, relatively, large, wetland, 'basins,', which, is, an, ongoing, conservation, 'strategy,', may, also, act, to, hedge, against, uncertainty, in, the, effects, of, climate, change])]). relacion([sujeto(['Here,', we]), verbo([have]), complemento([developed, a, ratiometric, imaging, method, for, measuring, monocyte, maturation, in, inflamed, mouse, lungs, in, situ, using, 'real-time', using, 2, -, photon, imaging, and, complementary, methods])]). relacion([sujeto(['We', visualized, that, while, undifferentiated, monocytes, were, predominantly]), verbo([found]), complemento([only, in, the, 'vasculature,', a, 'semi-differentiated', 'monocyte/macrophage', population, could, enter, the, tissue, and, resembled, more, mature, and, differentiated, populations, by, morphology, and, surface, phenotype])]). relacion([sujeto(['As', these, cells, entered, and, 'differentiated,', they, were, already, selectively, localized, near, inflamed, airways, and, their, entry, was]), verbo([associated]), complemento([with, changes, in, motility, and, morphology])]). relacion([sujeto(['We', were, able, to, visualize, these, during, the]), verbo([act]), complemento([of, 'differentiation,', a, process, that, can, be, demonstrated, in, this, way, to, be, faster, on, a, 'per-cell', basis, under, inflammatory, conditions])]). relacion([sujeto(['Finally,', our, in, situ, analyses, demonstrated, 'increases,', in, the, differentiating, 'cells,', for, both, antigen, uptake, and, the, ability, to]), verbo([mediate]), complemento([interactions, with, 'T', cells])]). relacion([sujeto(['This', 'work,', while, largely, confirming, proposed, models, for, in, situ, 'differentiation,']), verbo([provides]), complemento([important, in, situ, data, on, the, coordinated, 'site-specific', recruitment, and, differentiation, of, these, cells, and, helps, elaborate, the, predominance, of, immune, pathology, at, the, airways])]). relacion([sujeto(['Over', the, past, 'decades,', there]), verbo([has]), complemento([been, a, paradigm, shift, from, a, purely, biomedical, towards, a, 'bio-psycho-social', '(', 'BPS)', conception, of, disability, and, 'illness,', which, has, led, to, a, change, in, contemporary, healthcare])]). relacion([sujeto(['It', is, not, clear, whether, healthcare, professionals, show, the, necessary, skills, and, competencies, to]), verbo([act]), complemento([according, to, the, 'BPS', model])]). relacion([sujeto(['Statistical', coherence, was]), verbo([expressed]), complemento([in, 'item-total', correlations, and, in, 'Cronbach\'s', α, coefficient])]). relacion([sujeto(['Kynurenic', acid, '(', 'KYNA)', is, a, neuroactive, metabolite, of, tryptophan, formed, in, the, brain, and, in, the, 'periphery,', known, to, block, ionotropic, glutamate, receptors, and, α7, nicotinic, 'receptors,', and, to]), verbo([act]), complemento([as, a, ligand, of, 'G', 'protein-coupled', 'GPR35', receptors, and, human, aryl, hydrocarbon, '(', 'AHR)', receptors])]). relacion([sujeto(['KYNA', seems, to]), verbo([modulate]), complemento([a, number, of, mechanisms, involved, in, the, pathogenesis, of, schizophrenia, including, dopaminergic, transmission, in, mesolimbic, and, mesocortical, areas, or, glutamatemediated, neurotransmission])]). relacion([sujeto(['Available', data]), verbo([suggest]), complemento([that, antipsychotic, drugs, may, restore, balance, among, kynurenine, pathway, 'metabolites,', and, that, 'co-administration', of, glycine, with, antipsychotics, may, reduce, extrapyramidal, symptoms, in, patients, suffering, from, schizophrenia])]). relacion([sujeto(['Central', level, of, 'KYNA', may]), verbo([increase]), complemento([in, the, course, of, 'inflammation,', which, is, consistent, with, the, inflammatory, hypothesis, of, schizophrenia])]). relacion([sujeto(['Alterations', of, immune, response, and, disturbed, functioning, of, kynurenine, pathway, may]), verbo([lead]), complemento([to, disproportion, between, neuroprotective, and, neurotoxic, mechanisms, in, the, brain])]). relacion([sujeto(['Currently,', intense, research, efforts, are, focused, on, the, role, of, kynurenine, pathway, metabolites, in, pathogenesis, of, 'schizophrenia,', their, association, with, the, response, to, antipsychotic, 'treatment,', and, search, for, novel, medications]), verbo([modulating]), complemento([the, function, of, kynurenine, pathway])]). relacion([sujeto(['Because', the, relationship, between, physical, 'activity,', stress, and, obesity, measures]), verbo([has]), complemento([received, limited, 'attention,', this, study, examined, for, the, first, time, in, first, grade, schoolchildren, whether, physical, activity, and, fitness, moderate, the, relationship, between, psychosocial, stress, and, 'obesity-related', measures])]). relacion([sujeto(['Hierarchical', regression, analyses, were, calculated, to, test, whether, fitness, and, physical, activity]), verbo([act]), complemento([as, 'stress-buffers,', using, 'sex,', age, and, parental, education, as, covariates])]). relacion([sujeto(['This', study, shows, that, high, fitness, is]), verbo([associated]), complemento([with, less, unfavorable, body, composition, among, children, with, elevated, school, stress])]). relacion([sujeto(['In', 2015, ',', the, 'US', 'Congress', passed, legislation, entitled, the, 'Medicare', 'Access', and, 'CHIP', '[', 'Children\'s', 'Health', 'Insurance', 'Program]', 'Reauthorization', 'Act', '(', 'MACRA),', which]), verbo([led]), complemento([to, the, formation, of, two, reimbursement, 'paradigms:', the, 'merit-based', incentive, payment, system, '(', 'MIPS)', and, alternative, payment, models, '(', 'APMs)'])]). relacion([sujeto(['As', 'such,', 'MACRA', represents, an, unparalleled, acceleration, toward, reimbursement, models, that]), verbo([recognize]), complemento([value, rather, than, volume])]). relacion([sujeto(['Existing', 'APMs']), verbo([have]), complemento([yet, to, be, determined, as, eligible])]). relacion([sujeto(['We']), verbo([provide]), complemento([a, contextual, framework, of, the, healthcare, legislation, that, has, led, to, the, formation, of, current, health, policy, and, offer, recommendations, regarding, 'SGR', how, orthopaedic, surgeons, may, best, steer, through, such, reimbursement, models])]). relacion([sujeto(['Among', the, numerous, classes, of, these, 'drugs,', anthracyclines]), verbo([have]), complemento([been, studied, most, extensively, because, of, their, overt, cardiovascular, effects, and, the, high, associated, incidence, of, heart, failure])]). relacion([sujeto(['However,', 'CTX', might, also, be]), verbo([caused]), complemento([by, other, types, of, chemotherapeutic, 'agents,', including, alkylating, agents, '(', 'cyclophosphamide,', 'ifosfamide),', platinum, 'agents,', antimetabolites, '(', 5, -, 'fluorouracil,', 'capecitabine),', antibiotics, '(', 'mitoxantrone,', 'mitomycin,', 'bleomycin),', and, antimicrotubule, agents, '(', 'taxanes)'])]). relacion([sujeto(['Here,', we, review, the, 'incidence,', clinical, 'impact,', and, potential, mechanisms, of, 'CTX']), verbo([associated]), complemento([with, nonanthracycline, chemotherapy, used, for, cancer, patients])]). relacion([sujeto(['The', published, data, support, a, marked]), verbo([increase]), complemento([in, 'CTX', 'risk,', particularly, with, certain, drugs, such, as, 5, -, fluorouracil, and, cisplatin])]). relacion([sujeto(['Each', anticancer, regimen, is]), verbo([associated]), complemento([with, distinct, modes, of, heart, 'damage,', both, symptomatic, and, asymptomatic])]). relacion([sujeto(['However,', the, underlying, mechanisms, of, 'CTX']), verbo([have]), complemento([been, established, only, in, a, few, 'cases,', and, only, few, nonanthracycline, chemotherapeutics, '(', 'mitoxantrone,', 'mitomycin,', 'ifosfamide)', act, through, a, recognizable, mechanism, and, show, a, predictable, dose, dependence])]). relacion([sujeto(['Lastly,', nonanthracycline, chemotherapy, can]), verbo([induce]), complemento([both, chronic, 'lesions,', such, as, systolic, 'dysfunction,', and, acute, 'lesions,', such, as, the, ischemia, that, occurs, within, hours, or, days, after, treatment])]). relacion([sujeto(['An']), verbo([increased]), complemento([understanding, of, the, 'incidence,', 'mechanisms,', and, potential, therapeutic, targets, of, 'CTX', induced, by, various, nonanthracycline, chemotherapeutic, agents, is, clearly, required])]). relacion([sujeto(['Wildland', fire, fighting, is, a, 'high-risk', occupation]), verbo([requiring]), complemento([considerable, physical, and, psychological, demands])]). relacion([sujeto(['Multiple', agencies, publish, fatality, summaries, for, wildland, fire, 'fighters;', 'however,', the]), verbo([reported]), complemento([number, and, types, vary])]). relacion([sujeto(['Most', common]), verbo([causes]), complemento([of, death, in, all, systems, were, associated, with, 'aviation,', 'vehicles,', medical, 'events,', and, 'entrapments/burnovers'])]). relacion([sujeto(['The', data, show, 'that,', although, the, three, systems, often]), verbo([report]), complemento([similar, annual, summary, 'statistics,', events, captured, in, each, system, vary, each, year, depending, on, the, types, of, events, that, the, system, is, designed, to, 'track,', such, as, 'inclusion/exclusion', of, fatalities, associated, with, the, 'Hometown', 'Heroes', 'Survivor', 'Benefits', 'Act', of, 2003])]). relacion([sujeto(['Each', system, is, unique, and]), verbo([has]), complemento([varying, inclusion, and, exclusion, criteria, for, capturing, and, tracking, different, subsets, of, wildland, fire, fighter, tasks, and, duties])]). relacion([sujeto(['So', 'far,', the, availability, of, 'three-dimensional', '(', 3, 'D)', 'COFs', is, limited, and, more, importantly, only, one, type, of, covalent, bond]), verbo([has]), complemento([been, successful, used, for, 3, 'D', 'COF', materials])]). relacion([sujeto(['Here,', we]), verbo([report]), complemento([a, new, synthetic, strategy, based, on, dual, linkages, that, leads, to, 3, 'D', 'COFs'])]). relacion([sujeto(['Furthermore,', we, demonstrate, that, the, new, 3, 'D', 'COFs', comprise, both, acidic, and, basic, 'sites,', and]), verbo([act]), complemento([as, excellent, bifunctional, catalysts, for, 'one-pot', cascade, reactions])]). relacion([sujeto(['The', new, synthetic, strategy]), verbo([provides]), complemento([not, only, a, general, and, versatile, approach, to, synthesize, 3, 'D', 'COFs', with, sophisticated, structures, but, also, expands, the, potential, applications, of, this, promising, class, of, porous, materials])]). relacion([sujeto(['UV-visible', spectroscopy, studies, show, that, these, solvents]), verbo([have]), complemento([the, solubility, properties, of, heptane])]). relacion([sujeto(['PAOs', either, as, pure, solvents, or, as, additives, in, heptane]), verbo([act]), complemento([as, antileaching, 'agents,', decreasing, the, already, low, leaching, of, such, dyes, into, a, polar, phase, in, 'heptane/polar', solvent, mixtures])]). relacion([sujeto(['Further', studies, of, carboxylic, acid]), verbo([promoted]), complemento([dye, isomerization, in, heptane, and, a, 'PAO', show, that, low, molecular, weight, and, oligomeric, carboxylic, acids, are, kinetically, equivalent, at, accelerating, this, isomerization])]). relacion([sujeto(['The', results]), verbo([suggest]), complemento([that, these, and, other, hydrocarbon, oligomers, behave, as, solvents, like, their, low, molecular, weight, nonpolar, hydrocarbon, solvents, and, that, they, can, be, substituted, successfully, for, conventional, solvents, like, heptane])]). relacion([sujeto(['Although', all, current, antipsychotics]), verbo([act]), complemento([by, interfering, with, the, action, of, dopamine, at, dopamine, 'D2', 'receptors,', two, recent, reports, showed, that, 800, to, 1000, mg, of, cannabidiol, per, day, alleviated, the, signs, and, symptoms, of, 'schizophrenia,', although, cannabidiol, is, not, known, to, act, on, dopamine, receptors])]). relacion([sujeto(['Because', these, recent, clinical, findings, may, indicate, an, important, exception, to, the, general, rule, that, all, antipsychotics, interfere, with, dopamine, at, dopamine, 'D2', 'receptors,', the, present, study, examined, whether, cannabidiol]), verbo([acted]), complemento([directly, on, 'D2', 'receptors,', using, tritiated, domperidone, to, label, rat, brain, striatal, 'D2', receptors])]). relacion([sujeto(['It', was]), verbo([found]), complemento([that, cannabidiol, inhibited, the, binding, of, 'radio-domperidone', with, dissociation, constants, of, 11, nm, at, dopamine, 'D2High', receptors, and, 2800, nm, at, dopamine, 'D2Low', 'receptors,', in, the, same, biphasic, manner, as, a, dopamine, partial, agonist, antipsychotic, drug, such, as, aripiprazole])]). relacion([sujeto(['The', synthesis, of, specific, 'GSLs', depends, on, the, expression, of, distinctive, sets, of, 'GSL', synthesizing, enzymes, that, is, tightly]), verbo([regulated]), complemento([during, development])]). relacion([sujeto(['Several']), verbo([reports]), complemento([have, described, how, cell, surface, receptors, can, be, kept, in, a, resting, state, or, activate, alternative, signalling, events, as, a, consequence, of, their, interaction, with, 'GSLs'])]). relacion([sujeto(['Specific', 'GSLs,', 'indeed,', interface, with, specific, protein, domains, that, are]), verbo([found]), complemento([in, signalling, molecules, and, which, act, as, 'GSL', sensors, to, modify, signalling, responses])]). relacion([sujeto(['The', regulation, exerted, by, 'GSLs', on, signal, transduction, is, orthogonal, to, the, 'ligand-receptor', 'axis,', as, it, usually, does, not, directly, interfere, with, the, ligand]), verbo([binding]), complemento([to, receptors])]). relacion([sujeto(['Plant', phenolic, compounds, can]), verbo([act]), complemento([as, 'antioxidants,', structural, polymers, '(', 'lignin),', attractants, '(', flavonoids, and, 'carotenoids),', 'UV', screens, '(', 'flavonoids),', signal, compounds, '(', salicylic, 'acid,', 'flavonoids)', and, defense, response, chemicals, '(', 'tannins,', 'phytoalexins)'])]). relacion([sujeto(['Therefore,', it, is, beneficial, to, eat, such, plant, foods, that]), verbo([have]), complemento([a, high, antioxidant, compound, 'content,', which, will, cut, down, the, incidence, of, certain, chronic, 'diseases,', for, instance, 'diabetes,', cancers, and, cardiovascular, 'diseases,', through, the, management, of, oxidative, stress])]). relacion([sujeto(['Furthermore,', berries, and, other, fruits, with, 'low-amylase', and, 'high-glucosidase', inhibitory, activities, could, be, thought, of, as, candidate, food, items, in, the, control, of, the, early, stages, of, hyperglycemia]), verbo([associated]), complemento([with, type, 2, diabetes])]). relacion([sujeto(['Tobacco', smoke, contains, many, potentially, harmful, compounds, that, may]), verbo([act]), complemento([differently, and, at, different, stages, in, breast, cancer, development])]). relacion([sujeto(['The', focus, of, this, work, was, to, assess, the, possible, role, of, cigarette, smoking, '(', 'status,', 'dose,', duration, or, age, at, 'initiation)', and, polymorphisms, in, genes, coding, for, enzymes]), verbo([involved]), complemento([in, tobacco, carcinogen, metabolism, '(', 'CYP1A1,', 'CYP2A6)', or, in, 'DNA', repair, '(', 'XRCC1,', 'APEX1,', 'XRCC3', and, 'XPD)', in, breast, cancer, development])]). relacion([sujeto(['We']), verbo([found]), complemento([an, association, between, smoking, status, and, early, age, at, diagnosis, of, breast, cancer])]). relacion([sujeto(['Among', 'smokers,', invasive, carcinoma, subtype, incidence]), verbo([increased]), complemento([with, intensity, and, duration, of, smoking, '(', all, 'Ptrend', &, 'lt;', 0.05, ')'])]). relacion([sujeto(['When', smokers, were, stratified, by, smoking, 'duration,', we, only, observed, differences, in, 'long-term', 'smokers,', and, the, 'CYP1A1', 'Ile462Ile', genotype, was]), verbo([associated]), complemento([with, increased, risk, of, breast, cancer, '(', 'OR', =, 7.12, '(', 1.98, -, 25.59, ')', ')'])]). relacion([sujeto(['A', number, of, different, flavin, reductases, '(', 'FRs)']), verbo([have]), complemento([the, potential, to, supply, reduced, flavin, mononucleotide, to, both, 2, ',', 5, -, and, 3, ',', 6, -, diketocamphane, 'monooxygenase,', the, key, isoenzymic, 'two-component', monooxygenases, that, delineate, respectively, the, '(', +, ')', -, and, '(', -, ')', -, camphor, branches, of, the, convergent, degradation, pathway])]). relacion([sujeto(['Two', different, constitutive, 'chromosome-coded', ferric, reductases, able, to]), verbo([act]), complemento([as, 'FRs', can, serve, such, as, role, throughout, all, stages, of, 'camphor-dependent', 'growth,', whereas, 'Fred,', a, 'chromosome-coded', inducible, 'FR', can, only, play, a, potentially, significant, role, in, the, relatively, late, stages])]). relacion([sujeto(['Putidaredoxin', 'reductase,', an, inducible, 'CAM', 'plasmid-coded', flavoprotein, that, serves, an, established, role, as, a, redox, intermediate, for, 'plasmid-coded', cytochrome, 'P450', monooxygenase, also]), verbo([has]), complemento([the, potential, to, serve, as, an, important, 'FR', for, both, diketocamphane, monooxygenases, '(', 'DKCMOs)', throughout, most, stages, of, 'camphor-dependent', growth])]). relacion([sujeto(['The', benefits, of, dairy, consumption, seem, to, extend, beyond, its, significant, contribution, to]), verbo([ensuring]), complemento([nutrient, intake, adequacy, as, indicated, by, the, favourable, associations, with, several, health, outcomes, reported, by, different, studies])]). relacion([sujeto(['A', representative, subsample, of, 600, children, aged, 9, -, 13, years]), verbo([participating]), complemento([in, the, 'Healthy', 'Growth', 'Study', was, examined])]). relacion([sujeto([',', plasma, 'riboflavin,', methylmalonic, acid, and, total, homocysteine, 'concentrations),', dietary, calcium, intake, and, plasma, zinc, concentrations, that, could, possibly]), verbo([act]), complemento([as, effect, modifiers])]). relacion([sujeto(['Milk', consumption, was, positively]), verbo([associated]), complemento([with, the, number, of, stages, performed, in, the, endurance, run, test, '(', 'ERT)', '(', β, =, 0.1, ;, p, =, 0.017, ')', and, negatively, with, body, mass, index, '(', 'BMI)', '(', β, =, -, 0.1, ;, p, =, 0.014, ')', ',', after, adjusting, for, several, potential, confounders, and, effect, modifiers])]). relacion([sujeto(['Dietary', intakes, of, vitamin, 'B₂', and, 'B12', derived, from, milk, were, also, positively]), verbo([associated]), complemento([with, the, number, of, 'ERT', stages, '(', β, =, 0.1, ;, p, =, 0.015, and, β, =, 0.1, ;, p, =, 0.014, 'respectively)'])]). relacion([sujeto(['In', 'conclusion,', higher, intake, of, milk, as, well, as, vitamin, 'B₂', and, 'B12', derived, from, milk, were, independently]), verbo([associated]), complemento([with, higher, cardiorespiratory, fitness, in, 'Greek', preadolescents])]). relacion([sujeto(['The', key, roles, of, these, 'B-vitamins', in, substrate, 'oxidation,', energy, 'production,', haemoglobin, synthesis, and, erythropoiesis, could]), verbo([provide]), complemento([a, basis, for, interpreting, these, associations])]). relacion([sujeto(['It', was]), verbo([reported]), complemento([that, multiple, exon, skipping, '(', 'MES),', targeting, exon, 45, -, 55, of, the, 'DMD', 'gene,', might, improve, 'patients\'', symptoms, because, patients, who, have, a, genomic, deletion, of, all, these, exons, showed, very, mild, symptoms])]). relacion([sujeto(['Thus,', exon, 45, -, 55, skipping, treatments, for, 'DMD']), verbo([have]), complemento([been, proposed, as, a, potential, clinical, cure])]). relacion([sujeto(['Surprisingly,', the, 5, '\'', splice, sites, of, recently]), verbo([reported]), complemento(['post-transcriptional', introns, '(', remaining, introns, after, 'co-transcriptional', 'splicing)', act, as, splicing, donor, sites, for, 'MESs'])]). relacion([sujeto(['We', also, tested, exon, combinations, to, generate, 'DMD', circular, 'RNAs', '(', 'circRNAs)', and, determined, the, preferential, splice, sites, of, 'back-splicing,', which, are]), verbo([involved]), complemento([not, only, in, circRNA, 'generation,', but, also, in, 'MESs'])]). relacion([sujeto(['Our', results, fit, the, current, 'circRNA-generation', 'model,']), verbo([suggesting]), complemento([that, upstream, 'post-transcriptional', introns, trigger, 'MES', and, generate, circRNA, because, its, existence, is, critical, for, the, 'intra-intronic', interaction, or, for, extremely, distal, splicing])]). relacion([sujeto(['The']), verbo([finding]), complemento([that, small, 'non-coding', 'RNAs', '(', 'ncRNAs)', are, able, to, control, gene, expression, in, a, sequence, specific, manner, has, had, a, massive, impact, on, biology])]). relacion([sujeto(['Recent', improvements, in, high, throughput, sequencing, and, computational, prediction, methods]), verbo([have]), complemento([allowed, the, discovery, and, classification, of, several, types, of, ncRNAs])]). relacion([sujeto(['Based', on, their, precursor, 'structures,', biogenesis, pathways, and, modes, of, 'action,', ncRNAs, are, classified, as, small, interfering, 'RNAs', '(', 'siRNAs),', microRNAs, '(', 'miRNAs),', 'PIWI-interacting', 'RNAs', '(', 'piRNAs),', endogenous, small, interfering, 'RNAs', '(', 'endo-siRNAs', or, 'esiRNAs),', promoter]), verbo([associate]), complemento(['RNAs', '(', 'pRNAs),', small, nucleolar, 'RNAs', '(', 'snoRNAs)', and, 'sno-derived', 'RNAs'])]). relacion([sujeto([miRNAs]), verbo([act]), complemento([as, 'post-transcriptional', regulators, of, their, messenger, 'RNA', '(', 'mRNA)', targets, via, mRNA, degradation, 'and/or', translational, repression])]). relacion([sujeto(['However,', it, is, becoming, evident, that, miRNAs, also]), verbo([have]), complemento([specific, nuclear, functions])]). relacion([sujeto(['Although', available, data, detail, quite, precisely, the, effectors, of, this, 'activity,', the, mechanisms, by, which, miRNAs, identify, their, gene]), verbo([targets]), complemento([to, control, transcription, are, still, a, matter, of, debate])]). relacion([sujeto(['Here,', we, focus, on]), verbo([nuclear]), complemento([functions, of, miRNAs, and, on, alternative, mechanisms, of, target, 'recognition,', at, the, promoter, 'lavel,', by, miRNAs, in, carrying, out, transcriptional, gene, silencing])]). relacion([sujeto(['Excessive', sodium, intake, is]), verbo([associated]), complemento([with, both, hypertension, and, an, increased, risk, of, cardiovascular, 'events,', presumably, because, of, an, increase, in, extracellular, volume])]). relacion([sujeto(['Recent', experiments]), verbo([have]), complemento([shown, 'that,', other, than, regulation, by, the, 'kidney,', sodium, homeostasis, is, also, regulated, by, negatively, charged, glycosaminoglycans, in, the, skin, 'interstitium,', where, sodium, is, bound, to, glycosaminoglycans, without, commensurate, effects, on, extracellular, volume])]). relacion([sujeto(['Because', negatively, charged, glycosaminoglycans, are, abundantly, present, in, this, 'layer,', it, may]), verbo([act]), complemento([as, an, intravascular, buffer, compartment, that, allows, sodium, to, be, transiently, stored, '(', figure, 1, ')'])]). relacion([sujeto(['In', my, 'presentation,', 'I', will, focus, on, the, putative, role, of, the, endothelial, surface, layer, as, a, contributor, to, salt, 'sensitivity,', the, consequences, of, a, perturbed, endothelial, surface, layer, on, sodium, 'homeostasis,', and, the, endothelial, surface, layer, as, a, possible]), verbo([target]), complemento([for, the, treatment, of, hypertension, and, an, expanded, extracellular, volume])]). relacion([sujeto(['Pulmonary', arterial, hypertension, '(', 'PAH)', is, a, 'life-threatening', disorder, with, a, poor, prognosis, and]), verbo([causes]), complemento([pulmonary, vascular, remodeling, accompanied, with, increased, pulmonary, arterial, medial, wall, thickness, and, 'fibrosis,', which, leads, to, vascular, and, right, ventricular, '(', 'RV)', dysfunction])]). relacion([sujeto(['Recent', 'registries,', clinical, 'trials,', and, basic, researches]), verbo([have]), complemento([been, increasing, the, knowledge, of, 'PAH', and, it, would, contribute, to, potential, therapeutic, strategies, and, better, clinical, outcome])]). relacion([sujeto(['Total', 39, centers]), verbo([participated]), complemento([and, 625, patients, were, enrolled])]). relacion([sujeto(['This', study, compared, the, cumulative, survival, of, total, 43, 'PAH', patients, who, received]), verbo([targeted]), complemento([or, conventional, therapy])]). relacion([sujeto(['Data']), verbo([suggests]), complemento(['that,', although, the, survival, and, therapeutic, potential, of, all, three, 'MSCs', were, similar, with, regards, to, the, attenuation, of, 'MCT-induced', 'PAH', progression, in, 'rats,', each, 'MSCs', may, act, differently, via, distinct, molecular, mechanisms])]). relacion([sujeto(['Histone', deacetylases, '(', 'HDACs)']), verbo([act]), complemento([as, 'co-repressors', in, gene, transcription, by, erasing, the, acetylation, of, 'histones,', resulting, in, epigenetic, gene, silencing])]). relacion([sujeto(['Unexpectedly,', microarray, studies, uncovered, that, administration, of, 'HDAC', inhibitors]), verbo([decreased]), complemento([expression, of, some, genes, for, example, extracellular, matrix, 'proteins,', oxidative, 'stress-related', 'proteins,', 'cytokines,', chemokines, and, ion, 'transporters,', mostly, targets, of, corticoid, receptors])]). relacion([sujeto(['Valproic', acid, '(', 'VPA),', a, class, 'I', and, 'IIa', 'HDAC', inhibitor, administration, significantly]), verbo([decreased]), complemento(['corticoid-induced', hypertension])]). relacion([sujeto(['VPA', administration]), verbo([increased]), complemento([acetylation, level, of, 'Mineralocorticoid', receptor, '(', 'MR),', which, was, closely, related, with, decreased, binding, affinity, with, hormone, response, element, in, the, promoters, of, target, genes, such, as, glucocorticoid, induced, leucine, zipper, '(', 'Gilz)', and, serum, glucocorticoid, regulated, 'kinase-1', '(', 'Sgk-1)'])]). relacion([sujeto(['HDAC3', and, 'HDAC4', were]), verbo([interacted]), complemento([with, 'MR', after, stimulation, of, aldosterone, '(', 10, 'nmol/L)', for, 30, min])]). relacion([sujeto(['HDAC4', inhibitor, showed, no, effect, on, acetylation, level, and, promoter]), verbo([binding]), complemento([affinity, of, 'MR'])]). relacion([sujeto(['In', 'conclusion,', 'HDAC', inhibitors]), verbo([increased]), complemento([acetylation, of, corticoid, 'receptor,', resulted, in, decreased, transcriptional, activity, of, it, and, blocked, corticoid, 'induced-hypertension'])]). relacion([sujeto(['There', is, now, a, considerable, body, of, evidence, to]), verbo([suggest]), complemento([that, the, fat, cells, that, surround, blood, vessels, '(', perivascular, adipose, 'tissue,', 'PVAT)', can, influence, profoundly, arterial, tone, by, releasing, vasodilator, adipokines, which, can, act, locally, in, a, paracrine, fashion])]). relacion([sujeto(['In', healthy, lean, individuals, the, primary, vasodilator]), verbo([released]), complemento([appears, to, be, adiponectin, and, there, is, a, complex, interation, between, autonomic, nerve, firing, in, 'PVAT', and, the, release, of, nitric, oxide, from, adipocytes, and, an, increased, bioavailability, of, adiponectin])]). relacion([sujeto(['However', the, vasodilators, that, are]), verbo([released]), complemento([appear, to, be, agonist, dependent, and, adiponectin, is, certainly, increased, as, a, result, of, sympathomimetic, stimulation])]). relacion([sujeto(['Primarily', our, work]), verbo([has]), complemento([focused, on, the, role, of, sympathetic, nerves, running, through, 'PVAT', and, innovating, adipocytes, and, releasing, adiponectin])]). relacion([sujeto(['Electrical', field, stimulation, studies]), verbo([have]), complemento([demonstrated, clearly, the, release, of, adiponectin, and, the, induction, of, relaxation, which, is, abolished, using, 6, -, hydroxydopamine, or, tetrodotoxin, to, destroy, the, autonomic, nerve, fibres])]). relacion([sujeto(['In', obesity, there, is, evidence, of, 'beta-3', receptors, on, adipocytes, and, the]), verbo([loss]), complemento([of, vasodilator, activity, which, is, clearly, observed])]). relacion([sujeto(['In', some, models, of, obesity, there, is, also, evidence, of, an]), verbo([increase]), complemento([in, vasoconstrictor, prostaglandin, bioavailability, and, increased, contractility])]). relacion([sujeto(['This']), verbo([loss]), complemento([of, balance, between, vasodilatation, and, vasoconstriction, will, lead, to, an, increase, in, peripheral, resistance, which, will, decrease, glucose, uptake, in, skeletal, muscle, and, bring, about, a, rise, in, blood, 'pressure:', key, components, of, the, metabolic, syndrome])]). relacion([sujeto(['Hypertensive', patients]), verbo([have]), complemento([greater, chances, of, such, cardiovascular, events, as, 'stroke,', coronary, heart, 'disease,', heart, or, renal, 'failure,', peripheral, artery, 'disease,', and, dementia])]). relacion([sujeto(['It', is, also, well]), verbo([recognized]), complemento([that, diabetes, increases, the, cardiovascular, risks, in, concert, with, hypertension])]). relacion([sujeto(['Therefore,', main, goals, for, an, innovation, of, 'anti-hypertensive', therapy, would, be, to, achieve, further, risk, reduction, by]), verbo([targeting]), complemento([the, 'functional,', 'metabolic,', and, structural, alterations, associated, with, hypertension])]). relacion([sujeto(['Professors', 'Dzau', and, 'Braunwald', et, al, proposed, the, concept, of, &, 'quot;the', cardiovascular, disease, 'continuum"', in, 1991, ',', and, that, hypertension, may]), verbo([trigger]), complemento([the, chain, of, 'events,', leading, to, 'end-stage', heart, 'disease;', 'however,', this, concept, was, quite, new, at, that, 'time,', and, there, was, some, discussion, whether, &, 'quot;the', cardiovascular, disease, 'continuum"', is, true, or, not])]). relacion([sujeto(['Therefore,']), verbo([targeting]), complemento([oxidative, stress, and, inflammation, are, important, to, interrupt, the, cardiovascular, disease, continuum])]). relacion([sujeto(['However,', so, 'far,', neither, 'anti-oxidative', nor, 'anti-inflammation', strategy, can, work, well, to]), verbo([prevent]), complemento([hypertension, and, its, related, cardiovascular, diseases])]). relacion([sujeto(['Low-grade', inflammation]), verbo([has]), complemento([been, proposed, to, play, a, key, role, in, the, pathogenesis, of, 'hypertension,', and, both, innate, and, adaptive, immune, responses, may, participate, in, this, process])]). relacion([sujeto(['Recent', evidence, also, defined, important, roles, of, 'T-cell', and, 'T-cell-derived', cytokines]), verbo([associated]), complemento([with, angiotensin, '(', 'Ang)', 'II', and, catecholamine])]). relacion([sujeto(['We', expect, these, new, findings, could]), verbo([provide]), complemento([us, with, novel, avenues, to, beat, 'hypertension,', in, terms, of, 'anti-oxidative', stress, 'and/or', 'anti-inflammation'])]). relacion([sujeto(['Renin-angiotensin-aldosterone', system, '(', 'RAAS)', plays, a, significant, role, in, the, cardiovascular, disease, continuum]), verbo([interacting]), complemento([with, adrenergic, system, and, other, various, 'mediators,', and, thereby, 'RAAS', mediates, adaptive, and, maladaptive, responses, to, tissue, injury])]). relacion([sujeto(['Sympathetic', hyperactivity, and, the, activation, of, 'RAAS', may]), verbo([promote]), complemento([hypertension, or, work, as, an, amplifier, of, the, pressor, influence, of, other, factors, such, as, metabolic, factors])]). relacion([sujeto(['Therefore,', 'RAAS', and, sympathetic, nervous, system, are, the, major]), verbo([targets]), complemento([of, treatment, of, hypertension, and, its, related, cardiovascular, complications])]). relacion([sujeto(['The', two, main, interventional, 'approaches,', transcatheter, renal, denervation, and, baroreflex, activation, 'therapy,']), verbo([have]), complemento([been, used, in, clinical, practice, for, treatment, of, resistant, hypertension, and, the, renal, denervation, is, also, being, evaluated, for, treatment, of, various, 'comorbidities,', although, the, efficacy, of, invasive, 'sympatho-deactivating', interventions, have, not, yet, been, conclusively, validated])]). relacion([sujeto(['In', the, past, two, 'decades,', the, development, of, the, drugs, for, the, treatment, of, hypertension, and, cardiovascular, diseases]), verbo([has]), complemento([been, largely, focused, on, the, inhibitors, of, 'RAAS,', including, immunization, against, 'Ang', 'II'])]). relacion([sujeto(['Novel', pathways, beyond, the, classical, actions, of, 'RAAS,', the, angiotensin, converting, enzyme, '(', 'ACE)/Ang', 'II/Ang', 'II', type, 1, '(', 'AT1)', receptor, 'axis,']), verbo([have]), complemento([been, 'highlighted:', the, 'ACE2/Ang-(1-7)/Mas', receptor, axis, and, 'Ang', 'II', type, 2, '(', 'AT2)', receptor, as, a, new, opposing, axis, against, the, classical, 'RAS', axis, as, a, protective, arm, of, 'RAAS'])]). relacion([sujeto(['Moreover,', identification, of, alamandine, and, its, 'receptor,', 'Mas-related', 'G-protein', coupled, 'receptor,']), verbo([provides]), complemento([new, insights, for, the, understanding, of, the, physiological, and, pathophysiological, role, of, the, 'RAS'])]). relacion([sujeto(['Further', elucidation, of, the, regulatory, mechanisms, of, the, functions, of, new, protective, arm, of, 'RAS', beyond, the, classical, 'RAAS', could]), verbo([provide]), complemento([us, with, possibilities, for, the, development, of, novel, drugs, that, regulate, 'RAAS', in, a, more, sophisticated, 'manner,', thereby, treating, hypertensive, patients, and, achieving, cardiovascular, risk, reduction, more, efficiently])]). relacion([sujeto(['Agonists', of, protective, arm, of, 'RAS']), verbo([have]), complemento([been, developed, as, new, drugs, for, hypertension, and, several, drugs, of, the, agonists, of, protective, arm, of, 'RAS', are, now, in, clinical, trials])]). relacion([sujeto(['Several', novel, 'Ang', 'II', receptor]), verbo([interacting]), complemento([proteins, have, been, also, reported])]). relacion([sujeto(['AT1', 'receptor-associated', protein, '(', 'ATRAP)', was, cloned, by, us, as, specific]), verbo([binding]), complemento([protein, of, 'AT1', receptor, 'C-terminal,', and, we, and, others, reported, that, 'ATRAP', could, act, as, a, negative, regulator, in, 'AT1', 'receptor-mediated', effects, at, least, in, part, by, the, enhancement, of, 'AT1', receptor, internalization])]). relacion([sujeto(['We', cloned, 'AT2', receptor]), verbo([interacting]), complemento([protein, '(', 'ATIP)', as, a, protein, interacting, specifically, with, the, 'C-terminal', tail, of, the, 'AT2', receptor])]). relacion([sujeto(['We', and, others, demonstrated, that, 'ATIP']), verbo([enhanced]), complemento([an, important, role, of, 'AT2', 'receptor-mediated', wide, variety, of, pathophysiological, functions])]). relacion([sujeto(['Further', elucidation, of, the, functional, regulation, of, these, 'Ang', 'II', receptor]), verbo([associated]), complemento([proteins, including, their, transcriptional, 'control,', and, finding, possible, ligands, could, be, helpful, for, new, drug, developments])]). relacion([sujeto(['Classification', of, 'ARDS', severity, based, on, 'PaO2/FiO2', ratio, was]), verbo([associated]), complemento([with, an, increase, in, intensity, of, ventilatory, 'support,', 'NIV', 'failure,', and, 'Intensive', 'Care', 'Unit', '(', 'ICU)', mortality])]). relacion([sujeto(['NIV', use, was, independently]), verbo([associated]), complemento([with, increased, 'ICU', '(', 'HR', 1.446, ;, '[', 1.159, -, 1.805, ']', ')', ',', but, not, hospital, mortality])]). relacion([sujeto(['NIV', appears, to, be]), verbo([associated]), complemento([with, higher, 'ICU', mortality, in, patients, with, a, 'PaO2/FiO2', lower, than, 150, mmHg])]). relacion([sujeto(['An', 'over-reliance', of, 'broad-spectrum', insecticides]), verbo([led]), complemento([to, 'Helicoverpa', spp])]). relacion([sujeto(['Despite', adoption, of, these, 'practices,', insecticide, resistance, continued, to, develop, until, the, introduction, of, genetically, modified, cotton]), verbo([provided]), complemento([a, platform, for, augmenting, 'Integrated', 'Pest', 'Management', in, the, 'Australian', cotton, industry])]). relacion([sujeto(['Magic', 'tricks,', in, 'particular,']), verbo([have]), complemento([been, shown, to, activate, neural, circuits, that, underpin, motivation, or, 'problem-solving', 'and,', 'therefore,', could, be, beneficial, during, lectures])]). relacion([sujeto(['This', research, could, clarify, when, performance, can]), verbo([enhance]), complemento([or, disrupt, student, engagement])]). relacion([sujeto(['Circulating', vesicles, are, thought, to]), verbo([mediate]), complemento(['cell-to-cell', communication, and, their, 'RNA', cargo, can, act, as, regulatory, molecules])]). relacion([sujeto(['We']), verbo([found]), complemento([that, blood, plasma, sub, fractions, contain, not, only, extensive, set, of, microRNAs, but, also, fragments, of, other, cellular, 'RNAs:', 'rRNAs,', 'tRNAs,', 'mRNAs,', 'lncRNAs,', small, 'RNAs', including, 'RNAs', encoded, by, mtDNAs])]). relacion([sujeto(['The', 'Peninsula', 'Technology', 'Assessment', 'Group', was, commissioned, to]), verbo([act]), complemento([as, the, 'Evidence', 'Review', 'Group', '(', 'ERG)'])]). relacion([sujeto(['However,', in, the, 'intention-to-treat', 'analysis,', the, survival, advantage]), verbo([associated]), complemento([with, azacitidine, was, not, statistically, significant])]). relacion([sujeto(['Given', the, evidence]), verbo([provided]), complemento([in, the, 'submission,', azacitidine, did, not, fulfil, 'NICE\'s', 'end-of-life', criteria])]). relacion([sujeto(['The', health, care, system, of, the, 'United', 'States']), verbo([has]), complemento([been, in, a, period, of, dramatic, transformation, since, the, passage, of, the, 'Affordable', 'Care', 'Act', in, 2010, ',', and, the, rate, of, change, is, accelerating])]). relacion([sujeto(['Historically,', health, care, delivery, was, focused, on, the, efforts, of, independent, individual, providers, related, to, single, 'patients,', but, the, future, will]), verbo([require]), complemento([interprofessional, teamwork, to, achieve, successful, transformation])]). relacion([sujeto(['To', create, this, 'change,', there, are, several, critical, success, factors, for, academic, health, center, 'leaders,', including, creating, a, culture, of, 'collaboration,', becoming, &, 'quot;multipliers,"', embracing, 'innovation,', adhering, to, core, professional, 'ethics,', and, working, to]), verbo([promote]), complemento([resilience])]). relacion([sujeto(['UV-vis', diffuse, reflectance, spectra, confirm, redshift, in, the, optical, absorption, edge, of, nanocomposites, with]), verbo([increasing]), complemento([amount, of, 'multi-walled', carbon, nanotubes])]). relacion([sujeto(['The', photoluminescence, study]), verbo([reveals]), complemento([that, the, 'Fe-TiO2-multi-walled', carbon, nanotubes, nanocomposites, are, capable, to, generate, higher, rate, of, reactive, oxygen, species, species, than, that, of, other, nanocomposites])]). relacion([sujeto(['Our', experimental, results, demonstrated, that, the, 'Fe-TiO2-multi-walled', carbon, nanotubes, nanocomposites]), verbo([act]), complemento([as, efficient, antibacterial, agents, against, a, wide, range, of, microorganisms, to, prevent, and, control, the, persistence, and, spreading, of, bacterial, infections])]). relacion([sujeto(['Aryl', hydrocarbon, receptor, '(', 'AHR),', a, 'ligand-activated', transcription, 'factor,']), verbo([has]), complemento([been, studied, extensively, in, carcinogenesis, through, the, genomic, pathway])]). relacion([sujeto(['In', recent, 'years,', 'AHR']), verbo([has]), complemento([also, been, reported, to, exert, positive, or, negative, effects, on, 'epithelial-mesenchymal', transition, '(', 'EMT),', the, crucial, step, in, tumor, malignant, progression])]). relacion([sujeto(['Overexpression', of, 'wild-type', 'AHR', in, 'H1299', cells, '(', 'AHR', poorly, 'expressed,', potently, 'invasive)', not, only, accelerated, mesenchymal, vimentin, 'degradation,', but, also]), verbo([prevented]), complemento([cell, invasion, in, vitro, and, in, vivo])]). relacion([sujeto(['In', the, absence, of, 'AHR', 'agonists,', the, overexpressed, 'AHR', protein, was, predominantly, localized, in, the, 'cytoplasm,', where, it]), verbo([interacted]), complemento([with, vimentin, and, functioned, as, an, 'E3', ubiquitin, ligase])]). relacion([sujeto(['In', 'contrast,', silencing, of, 'AHR', in, 'A549', cells, '(', 'AHR', highly, 'expressed,', weakly, 'invasive)', resulted, in, the, downregulation, of, epithelial, biomarkers, '(', 'E-cadherin', and, 'claudin-1),', augmentation, of, mesenchymal, vimentin, 'level,', and, 'GSK3β', 'Ser-9', 'hyper-phosphorylation,', which]), verbo([led]), complemento([to, enhanced, invasiveness])]). relacion([sujeto(['This', work, demonstrates, that, 'cytoplasmic,', resting, 'AHR', protein, may]), verbo([act]), complemento([as, an, 'EMT', suppressor, via, a, 'non-genomic', pathway])]). relacion([sujeto(['Depletion', of, cytoplasmic, 'AHR', content, represents, a, potential, switch, for, 'EMT,', thereby]), verbo([leading]), complemento([to, the, scattering, of, tumor, cells])]). relacion([sujeto(['Medical']), verbo([reports]), complemento([are, required, to, support, court, applications, to, appoint, a, deputy, to, make, decisions, on, behalf, of, a, person, who, has, lost, mental, capacity])]). relacion([sujeto(['The', doctor, writing, such, a, medical]), verbo([report]), complemento([needs, to, be, able, to, systematically, assess, the, mental, capacity, of, the, person, in, 'question,', in, order, to, gather, the, necessary, evidence, for, the, 'Court', to, make, a, decision])]). relacion([sujeto(['If', the, medical]), verbo([report]), complemento([is, not, 'adequate,', the, application, will, be, rejected, and, the, appointment, of, the, deputy, delayed])]). relacion([sujeto(['Aims', and, method, 'The', need, for, an, 'age-appropriate', 'in-patient', service, for, 16, -, to, 17, -, 'year-olds']), verbo([led]), complemento([to, the, development, of, a, 6, -, bed, acute, admissions, unit, in, a, 'non-metropolitan', county, in, the, 'UK'])]). relacion([sujeto(['We']), verbo([provide]), complemento([a, descriptive, evaluation, of, the, first, 2, years, of, its, operation])]). relacion([sujeto(['Clinical', implications, 'The', unit]), verbo([provides]), complemento([an, accessible, and, effective, 'age-appropriate', service, and, is, likely, to, constitute, an, important, component, of, the, comprehensive, child, and, adolescent, mental, health, service, strategy, in, the, county])]). relacion([sujeto(['Over', the, last, 'decade,', patient, volumes, in, the, emergency, department, '(', 'ED)']), verbo([have]), complemento([grown, disproportionately, compared, to, the, increase, in, staffing, and, resources, at, the, 'Toronto', 'Western', 'Hospital,', an, academic, tertiary, care, centre, in, 'Toronto,', 'Canada'])]). relacion([sujeto(['The', resultant, congestion]), verbo([has]), complemento([spilled, over, to, the, 'ED', waiting, 'room,', where, medically, undifferentiated, and, potentially, unstable, patients, must, wait, until, a, bed, becomes, available])]). relacion([sujeto(['The', aim, of, this, quality, improvement, project, was, to]), verbo([decrease]), complemento([the, 90, th, percentile, of, wait, time, between, triage, and, bed, assignment, '(', 'time-to-bed)', by, 'half,', from, 120, to, 60, 'minutes,', for, our, highest, acuity, patients])]). relacion([sujeto(['We', then, generated, change, ideas, to, address, two, main, underlying]), verbo([causes]), complemento([of, 'ED', 'congestion:', unnecessary, patient, utilization, of, 'ED', beds, and, communication, breakdown, causing, bed, turnaround, delays])]). relacion([sujeto(['The', most, significant]), verbo([gains]), complemento([were, made, by, improving, communication, 'strategies:', small, gains, were, achieved, through, the, optimization, of, 'in-house', digital, information, management, 'systems,', while, significant, improvements, were, achieved, through, the, implementation, of, a, 'low-tech', direct, contact, mechanism, '(', a, 'two-way', radio, or, 'walkie-talkie)'])]). relacion([sujeto(['In', the, 'post-intervention', 'phase,', 'time-to-bed', for, the, 90, th, percentile, of, 'high-acuity', patients]), verbo([decreased]), complemento([from, 120, minutes, to, 66, 'minutes,', with, special, cause, variation, showing, a, significant, shift, in, the, weekly, measurements])]). relacion([sujeto(['Frequent,', preventable, medical, errors, can]), verbo([have]), complemento([an, adverse, effect, on, patient, safety, and, quality, as, well, as, leading, to, wasted, resources])]). relacion([sujeto(['At', the, 'Riyadh', 'Regional', 'Laboratory', of, the, 'Ministry', of, 'Health,', we]), verbo([found]), complemento([that, there, was, an, average, of, 2.31, errors, per, 1000, processed, 'samples;', these, errors, had, occurred, during, the, 'pre-analytical', stage])]). relacion([sujeto(['We', decided, to, carry, out, an, improvement, project, where, we, applied, a, systematic, approach, to, identify, and, analyse, the, root]), verbo([causes]), complemento([of, the, problem, using, quality, tools, such, as, a, process, flowchart, and, a, 'fish-bone', diagram])]). relacion([sujeto(['The', 'Model', for, 'Improvement', was, used, and, several, 'PDSA', '(', 'Plan,', 'Do,', 'Study,', 'Act)', cycles, were, run, to, test, interventions, which, aimed, to]), verbo([prevent]), complemento([laboratory, processing, errors, and, mistakes])]). relacion([sujeto(['The', 'HITECH', 'Act', 'Stage', 2, initiative]), verbo([provided]), complemento([incentive, and, motivation, for, healthcare, providers, to, encourage, their, 'Electronic', 'Medical', 'Record', '(', 'EMR)', vendors, to, implement, data, exchanges, with, public, 'health,', with, the, expected, result, being, timely, awareness, of, health, risks])]). relacion([sujeto(['The', empowerment, nugget, in, the, 'HITECH', 'Act', is, not, in, the, compliance]), verbo([reporting]), complemento([to, public, health])]). relacion([sujeto(['The', ability, for, public, health, to]), verbo([retain]), complemento([current, immunization, records, of, individuals, from, a, variety, of, providers, supports, their, program, goals, to, increase, immunization, rates, and, mitigate, the, risk, of, 'vaccine-preventable', disease, '(', 'VPD)'])]). relacion([sujeto(['The', ability, for, providers, to, receive, at, the, point, of, service, more, complete, immunization, histories, integrated, with, decision, support]), verbo([enhances]), complemento([their, delivery, of, 'care,', thereby, reducing, the, risk, of, 'VPD', to, their, patients])]). relacion([sujeto(['Indirectly', payers, benefit, through, healthcare, cost, savings, and, when, the, focus, is, expanded, from, a, health, model, to, a, business, 'model,', there, are, significant, return, on, investment, '(', 'ROI)', opportunities, that, exponentially]), verbo([increase]), complemento([the, value, of, a, 'bi-directional', immunization, data, exchange])]). relacion([sujeto(['This', paper, will]), verbo([provide]), complemento([descriptions, of, case, examples, to, demonstrate, the, value, of, electronic, data, exchanges, when, pharmacy, immunization, providers, and, public, health, work, together])]). relacion([sujeto(['Antimicrobial', peptides, '(', 'AMPs)', are, a, 'wide-ranging', class, of, 'host-defense', molecules, that]), verbo([act]), complemento([early, to, contest, against, microbial, invasion, and, challenge])]). relacion([sujeto(['Biosynthesis', of, the, glycopeptide, antibiotics, centres, of, the, combination, of, peptide, 'synthesis,']), verbo([mediated]), complemento([by, a, 'non-ribosomal', peptide, 'synthetase,', and, the, crosslinking, of, aromatic, side, chains, of, the, 'peptide,', mediated, by, the, action, of, a, cascade, of, 'Cytochrome', 'P450s'])]). relacion([sujeto(['Here,', we]), verbo([report]), complemento([the, first, example, of, in, vitro, activity, of, 'OxyE,', which, catalyses, the, 'F-O-G', ring, formation, reaction, in, teicoplanin, biosynthesis])]). relacion([sujeto(['OxyE', was]), verbo([found]), complemento([to, only, act, after, an, initial, 'C-O-D', crosslink, is, installed, by, 'OxyB', and, to, require, an, interaction, with, the, unique, 'NRPS', domain, from, glycopeptide, antibiotic, -, the, 'X-domain', -, in, order, to, display, catalytic, activity])]). relacion([sujeto(['This', work, demonstrates, that, complex, enzymatic, cascades, from, glycopeptide, antibiotic, biosynthesis, can, be, reconstituted, in, vitro, and]), verbo([provides]), complemento([new, insights, into, the, biosynthesis, of, these, important, antibiotics])]). relacion([sujeto(['We', previously]), verbo([reported]), complemento([that, the, human, 'HER2', gene, encodes, the, intronic, microRNA, 'mir-4728,', which, is, overexpressed, together, with, its, oncogenic, host, gene, and, may, act, independently, of, the, 'HER2', receptor])]). relacion([sujeto(['More', 'recently,', we, also]), verbo([reported]), complemento([that, the, oncogenic, 'miR-21-5p', is, regulated, by, 3, '\'', tailing, and, trimming, by, the, 'non-canonical', 'poly(A)', polymerase, 'PAPD5', and, the, ribonuclease, 'PARN'])]). relacion([sujeto(['Here', we, demonstrate, a, dual, function, for, the, 'HER2', locus, in, upregulation, of, 'miR-21-5p;', while, 'HER2', signalling]), verbo([activates]), complemento([transcription, of, 'mir-21,', 'miR-4728-3p', specifically, stabilises, 'miR-21-5p', through, inhibition, of, 'PAPD5'])]). relacion([sujeto(['Our', results, establish, a, new, and, unexpected, oncogenic, role, for, the, 'HER2', locus, that, is, not, currently, being]), verbo([targeted]), complemento([by, any, 'anti-HER2', therapy])]). relacion([sujeto(['Aqueous', miscible, organic, layered, double, hydroxides, '(', 'AMO-LDHs)', can]), verbo([act]), complemento([as, organophilic, inorganic, flame, retardant, nanofillers, for, unmodified, 'non-polar', polymers])]). relacion([sujeto(['A', synergistic, effect, between, the, 'AMO-LDH', and, 'OCNT', was, 'observed;', this, endows, the, hybrid, material, with]), verbo([enhanced]), complemento([flame, 'retardancy,', thermal, 'stability,', and, mechanical, properties])]). relacion([sujeto(['The', thermal, stability, of, polypropylene, '(', 'PP)', was, significantly]), verbo([enhanced]), complemento([by, adding, 'AMO-LDH-OCNT', hybrids])]). relacion([sujeto(['For', 'PP', mixed, with, 'AMO-LDH-OCNT', hybrids, to, produce, a, composite, with, 10, 'wt%', 'LDH', and, 2, 'wt%', 'OCNT,', the, 50, '%', weight]), verbo([loss]), complemento([temperature, was, increased, by, 43, °, 'C'])]). relacion([sujeto(['Further,', a, system, with, 10, 'wt%', of, 'AMO-LDH', and, 1, 'wt%', 'OCNT', showed, a, peak, heat]), verbo([release]), complemento([rate, '(', 'PHRR)', reduction, of, 40, '%', ',', greater, than, the, 'PHRR', reduction, with, 'PP/20', 'wt%', 'AMO-LDH', '(', 31, '%', ')'])]). relacion([sujeto(['The', degree, of, dispersion, '(', 'mixability)', between, 'AMO-LDH', and, 'OCNT']), verbo([has]), complemento([a, significant, effect, on, the, flame, retardant, performance, of, the, hybrids])]). relacion([sujeto(['In', 'addition,', the, incorporation, of, 'AMO-LDH-OCNT', hybrids]), verbo([led]), complemento([to, better, mechanical, 'properties,', such, as, higher, tensile, strength, '(', 27.5, 'MPa)', and, elongation, at, break, '(', 17.9, '%', ')', ',', than, those, composites, containing, only, 'AMO-LDH', '(', 25.6, 'MPa', and, 7.5, '%', ',', 'respectively)'])]). relacion([sujeto(['Amyloid-β', oligomers, '(', 'AβO)', are, species, mainly]), verbo([involved]), complemento([in, the, synaptic, and, cognitive, dysfunction, in, 'Alzheimer\'s', disease])]). relacion([sujeto(['Although', their, action]), verbo([has]), complemento([been, described, mainly, at, neuronal, 'level,', it, is, now, clear, that, glial, cells, govern, synaptic, activity, in, their, resting, 'state,', contributing, to, new, learning, and, memory, establishment])]). relacion([sujeto(['In', 'contrast,', when, 'activated,', they, may]), verbo([lead]), complemento([to, synaptic, and, cognitive, dysfunction])]). relacion([sujeto(['Using', a, reliable, acute, 'AβO-mediated', mouse, model, of, 'AD,', we, explored, whether, the, memory, alteration, 'AβOs']), verbo([induce]), complemento([relies, on, the, activation, of, glial, 'cells,', and, if, 'Toll-like', receptor, 4, '(', 'TLR4),', pivotal, in, the, initiation, of, an, immune, 'response,', is, involved])]). relacion([sujeto(['C57', naïve, mice, were, given, a, single, intracerebroventricular, injection, of, synthetic, 'AβO-containing', solution, '(', 1, 'μM),', which]), verbo([induces]), complemento([substantial, impairment, in, the, establishment, of, recognition, memory])]). relacion([sujeto(['After', that, we, explored, the, efficacy, of, 'pre-treatment', with, 'anti-inflammatory', drugs, '(', indomethacin, and, an, 'IL-1β', receptor, 'antagonist)', to]), verbo([prevent]), complemento([impairment, in, the, novel, object, recognition, 'task,', and, compared, 'AβO\'s', effects, in, 'TLR4', knockout, mice])]). relacion([sujeto(['A', single, 'AβO', injection, rapidly]), verbo([activated]), complemento([glial, cells, and, increased, 'pro-inflammatory', cytokine, expression])]). relacion([sujeto(['Both', 'anti-inflammatory', drugs]), verbo([prevented]), complemento([the, 'AβO-mediated', impairment, in, memory, establishment])]). relacion([sujeto(['These', data]), verbo([provide]), complemento([new, information, on, 'AβO\'s', mechanism, of, 'action,', indicating, that, besides, direct, action, at, the, 'synapses,', they, also, act, through, the, immune, 'system,', with, 'TLR4', playing, a, major, role])]). relacion([sujeto(['This']), verbo([suggests]), complemento([that, in, a, potential, therapeutic, setting, inflammation, must, be, considered, as, well])]). relacion([sujeto(['Chromium', allergy, is, a, common, occupational, skin, disease]), verbo([mediated]), complemento([by, chromium, '(', 'VI)-specific', 'T', cells, that, induce, 'delayed-type', hypersensitivity, in, sensitized, individuals])]). relacion([sujeto(['Additionally,', chromium, '(', 'VI)', can]), verbo([act]), complemento([as, an, irritant])]). relacion([sujeto(['Both', responses, critically]), verbo([require]), complemento([innate, immune, 'activation,', but, if, and, how, chromium, '(', 'VI)', elicits, this, signal, is, currently, unclear])]). relacion([sujeto(['Using', human, 'monocytes,', primary, human, 'keratinocytes,', and, murine, dendritic, cells, we, show, that, chromium, '(', 'VI)', compounds, fail, to]), verbo([trigger]), complemento([direct, proinflammatory, activation, but, potently, induce, processing, and, secretion, of, 'IL-1β'])]). relacion([sujeto(['IL-1β']), verbo([release]), complemento([required, priming, by, 'phorbol-ester', or, 'toll-like', receptor, stimulation, and, was, prevented, by, inhibition, of, 'K(+)', 'efflux,', 'NLRP3', depletion, or, 'caspase-1', 'inhibition,', identifying, chromium, '(', 'VI)', as, a, hapten, activator, of, the, 'NLRP3', inflammasome])]). relacion([sujeto(['Inflammasome', activation, was, initiated, by, mitochondrial, reactive, oxygen, species, production]), verbo([triggered]), complemento([by, chromium, '(', 'VI),', as, indicated, by, sensitivity, to, treatment, with, the, 'ROS', scavenger, 'N-acetyl', cysteine, and, a, coinciding, failure, of, 'K(+)', 'efflux,', 'caspase-1,', or, 'NLRP3', inhibition, to, prevent, mitochondrial, reactive, oxygen, species, accumulation])]). relacion([sujeto(['IL-1β']), verbo([release]), complemento([further, correlated, with, cytotoxicity, that, was, secondary, to, reactive, oxygen, 'species,', 'K(+)', 'efflux,', and, 'NLRP3', activation])]). relacion([sujeto(['Trivalent', chromium, was, unable, to]), verbo([induce]), complemento([mitochondrial, reactive, oxygen, species, 'production,', inflammasome, 'activation,', and, 'cytotoxicity,', suggesting, that, oxidation, 'state-specific', differences, in, mitochondrial, reactivity, may, determine, inflammasome, activation, and, 'allergic/irritant', capacity, of, different, chromium, compounds])]). relacion([sujeto(['The', mechanism, by, which, anesthetics, might]), verbo([act]), complemento([on, the, developing, brain, in, order, to, cause, long, term, deficits, remains, incompletely, understood])]). relacion([sujeto(['The', hippocampus]), verbo([has]), complemento([been, identified, as, a, structure, that, is, likely, to, be, 'involved,', as, rodent, models, show, numerous, deficits, in, behavioral, tasks, of, learning, that, are, 'hippocampal-dependent'])]). relacion([sujeto(['Intriguingly,', neurogenesis, is, a, major, developmental, event, that, occurs, during, postulated, windows, of, vulnerability, to, developmental, anesthetic, neurotoxicity, across, the, different, species, in, which, it]), verbo([has]), complemento([been, studied])]). relacion([sujeto(['While', there, is, abundant, evidence, that, anesthetics]), verbo([act]), complemento([to, suppress, neurogenesis, at, several, different, 'phases,', evidence, of, a, causal, link, between, these, effects, and, any, change, in, learning, behavior, remains, elusive])]). relacion([sujeto(['Whole-cell', imprinted, polymers]), verbo([have]), complemento([the, potential, to, be, applied, as, recognition, elements, in, biosensors, for, selective, bacterial, detection])]). relacion([sujeto(['In', this, 'paper,', we]), verbo([report]), complemento([on, the, use, of, 3, -, aminophenylboronic, acid, '(', 3, -, 'APBA)', for, the, electrochemical, fabrication, of, a, 'cell-imprinted', polymer, '(', 'CIP)'])]). relacion([sujeto(['The', use, of, a, monomer, bearing, a, boronic, acid, 'group,', with, its, ability, to, specifically]), verbo([interact]), complemento([with, 'cis-diol,', allowed, the, formation, of, a, polymeric, network, presenting, both, morphological, and, chemical, recognition, abilities])]). relacion([sujeto(['A', particularly, beneficial, feature, of, the, proposed, approach, is, the, reversibility, of, the, 'cis-diol-boronic', group, 'complex,', which, facilitates, easy]), verbo([release]), complemento([of, the, captured, bacterial, cells, and, subsequent, regeneration, of, the, 'CIP'])]). relacion([sujeto(['Staphylococcus', epidermidis, was, used, as, the, model]), verbo([target]), complemento([bacteria, for, the, 'CIP', and, electrochemical, impedance, spectroscopy, '(', 'EIS)', was, explored, for, the, 'label-free', detection, of, the, target, bacteria])]). relacion([sujeto(['A', selectivity, study, also, showed, that, the, 'CIP', could, discriminate, its]), verbo([target]), complemento([from, 'non-target', bacteria, having, similar, shape])]). relacion([sujeto(['The', 'CIPs', had, high, affinity, and, specificity, for, bacterial, detection, and]), verbo([provided]), complemento([a, switchable, interface, for, easy, removal, of, bacterial, cell])]). relacion([sujeto(['This', study, aimed, to, determine, whether, heat, stress, '(', 'HS)', could]), verbo([induce]), complemento([autophagy, in, immature, boar, 'Sertoli', cells, '(', 'SCs)', and, test, whether, 'HS-induced', autophagy, could, regulate, lactate, secretion, by, 'SCs'])]). relacion([sujeto(['The', ratio, of, 'LC3B-II', to, 'LC3B-I', and, the, mRNA, transcript, levels, of, 'LC3B', showed, 'time-dependent', changes, 0, to, 48, &, 'nbsp;hours', after, 'HS', 'treatment,', which, peaked, at, 24, &, 'nbsp;hours', and]), verbo([increased]), complemento([by, 30.25, '%', or, 260, '%', ',', 'respectively,', compared, with, control, 'SCs'])]). relacion([sujeto(['In', 'addition,', 'LY294002', '(', 20, &, 'nbsp;μM)', significantly]), verbo([inhibited]), complemento([changes, in, ratio, of, 'LC3B-II', to, 'LC3B-I,', 'LC3B', mRNA, transcript, 'levels,', and, autolysosome, formation])]). relacion([sujeto(['It', also, resulted, in, significantly, less, lactate, secretion, and]), verbo([increased]), complemento([apoptosis, but, showed, no, effect, on, 'B-cell', 'lymphoma-2', expression, in, 'heat-treated', immature, 'SCs'])]). relacion([sujeto(['These', findings, indicated, that, 'HS-induced', autophagy]), verbo([regulates]), complemento([lactate, secretion, by, inhibiting, apoptosis, and, increasing, mRNA, transcript, and, protein, levels, of, 'SLC2A3,', 'LDHA,', and, 'SLC16A1,', which, suggests, that, 'HS-induced', autophagy, may, enhance, lactate, secretion, by, 'SCs'])]). relacion([sujeto(['In', 'Huntington\'s', disease, '(', 'HD),', neurotoxicity, correlates, with, an]), verbo([increased]), complemento([aggregation, propensity, of, a, polyglutamine, '(', 'polyQ)', expansion, in, exon, 1, of, mutant, huntingtin, protein, '(', 'mHtt)'])]). relacion([sujeto(['In', 'vitro,', the, flanking, domains]), verbo([have]), complemento([opposing, effects, on, the, conformation, and, stabilities, of, oligomers, and, amyloid, fibrils])]). relacion([sujeto(['The', 'N-terminal', 'N17']), verbo([promotes]), complemento([amyloid, fibril, 'formation,', while, the, 'C-terminal', 'Proline', 'Rich', 'Domain', destabilizes, fibrils, and, enhances, oligomer, formation])]). relacion([sujeto(['However,', in, neurons, both, domains]), verbo([act]), complemento([synergistically, to, engage, protective, chaperone, and, degradation, pathways, promoting, mHtt, proteostasis])]). relacion([sujeto(['Herein', we]), verbo([report]), complemento([on, the, multicomponent, synthesis, of, a, novel, 'imidazole-based', 'compound,', able, to, act, efficiently, as, a, minimalist, 'β-strand', mimic])]). relacion([sujeto(['Diabetic', neuropathy]), verbo([has]), complemento([a, profound, impact, in, the, quality, of, life, of, patients, who, frequently, complain, of, pain])]). relacion([sujeto(['The', effects, of, diabetes, at, the, central, nervous, system, are, currently, considered]), verbo([causes]), complemento([of, 'DPN'])]). relacion([sujeto(['Management', of, 'DNP', may, be, achieved, by, antidepressants, that]), verbo([act]), complemento([on, serotonin, '(', 5, -, 'HT)', 'uptake,', namely, specific, serotonin, reuptake, inhibitors])]). relacion([sujeto(['The', rostroventromedial, medulla, '(', 'RVM)', is, a, key, pain, control, center]), verbo([involved]), complemento([in, descending, pain, modulation, at, the, spinal, cord, through, local, release, of, 5, -, 'HT', and, plays, a, peculiar, role, in, the, balance, of, bidirectional, control, '(', i])]). relacion([sujeto(['This', review, discusses, recently, uncovered, neurobiological, mechanisms, that]), verbo([mediate]), complemento([nociceptive, modulation, from, the, 'RVM', during, diabetes, installation])]). relacion([sujeto(['In', early, phases, of, the, 'disease,', facilitation, of, pain, modulation, from, the, 'RVM', prevails, through, a, triplet, of, mechanisms, which, include]), verbo([increase]), complemento([in, serotonin, expression, at, the, 'RVM', and, consequent, rise, of, serotonin, levels, at, the, spinal, cord, and, upregulation, of, local, facilitatory, 5, 'HT3', 'receptors,', enhancement, of, spontaneous, activity, of, facilitatory, 'RVM', neurons, and, 'up-regulation', of, the, expression, of, transient, receptor, potential, vanilloid, type, 1, '(', 'TRPV1)', receptor])]). relacion([sujeto(['With', the, progression, of, diabetes, the, alterations, in, the, 'RVM']), verbo([increase]), complemento(['dramatically,', with, oxidative, stress, and, neuronal, death, associated, to, 'microglia-mediated', inflammation])]). relacion([sujeto(['In', a, manner, similar, to, other, central, 'areas,', like, the, 'thalamus,', the, 'RVM', is, likely, to, be, a, &, 'quot;pain', 'generator/amplifier"', during, 'diabetes,', accounting, to]), verbo([increase]), complemento(['DNP'])]). relacion([sujeto(['Early', interventions, in, 'DNP', prevention, using, strategies, that, simultaneously, tackle, the, exacerbation, of, 5, -, 'HT3', spinal, receptors, and, of, microglial, 'RVM', 'activity,', namely, those, that]), verbo([increase]), complemento([the, levels, of, 'anti-inflammatory', 'cytokines,', should, be, considered, in, the, future, of, 'DNP', treatment])]). relacion([sujeto(['High', inbreeding, was, consistently, 'found,']), verbo([suggesting]), complemento([that, parents, often, develop, from, meiospores, produced, by, the, same, fruitbody])]). relacion([sujeto(['Thus,', we, postulate, that, germlings, from, the, soil, spore, bank]), verbo([act]), complemento([as, paternal, partners])]). relacion([sujeto(['Paternal', genetic, diversity, and, outbreeding, were, higher, in, plantations, than, in, spontaneous, 'truffle-grounds,', perhaps, because, truffle, growers, disperse, fruitbodies, to]), verbo([maintain]), complemento([inoculation, in, plantations])]). relacion([sujeto(['A', simple, 'base-mediated', 'one-pot', synthesis, of, 3, ',', 5, -, disubstituted, 1, ',', 2, ',', 4, -, oxadiazoles, from, 'nitriles,', aldehydes, and, hydroxylamine, hydrochloride]), verbo([has]), complemento([been, 'developed,', in, which, the, aldehydes, act, as, both, substrates, and, oxidants])]). relacion([sujeto(['The', reactions, include, three, sequential, 'procedures:', 'base-promoted', intermolecular, addition, of, hydroxylamine, to, nitrile, to]), verbo([lead]), complemento([to, 'amidoxime,', treatment, of, the, amidoxime, with, an, aldehyde, to, form, 4, ',', 5, -, 'dihydro-1,2,4-oxadiazole,', and, oxidization, of, the, 4, ',', 5, -, 'dihydro-1,2,4-oxadiazole', by, using, another, aldehyde, to, afford, 1, ',', 2, ',', 4, -, oxadiazole])]). relacion([sujeto(['Magnetic', 'nanoparticle-embedded', coordination, polymers, could]), verbo([act]), complemento([as, mimics, for, zinc, ion, transporters, for, targeted, cancer, therapy])]). relacion([sujeto(['Compared', with, traditional, zinc, 'ionophores,', our, system, could, realize]), verbo([targeted]), complemento([and, internal, environment, responsive, transport, of, zinc, ions, to, suppress, the, tumour, growth, while, minimizing, nonspecific, injury, to, normal, tissues])]). relacion([sujeto(['In', this, 'paper,', we]), verbo([report]), complemento([an, electrochemical, system, for, dynamic, control, of, cell, 'catch-and-release,', which, is, based, on, the, 'redox-controlled', 'host-guest', interaction])]). relacion([sujeto(['Experimental', results]), verbo([reveal]), complemento([that, the, interaction, between, guest, molecule, '(', 'ferrocene,', 'Fc)', and, host, molecule, '(', 'β-cyclodextrin,', 'β-CD)', is, highly, sensitive, to, electrochemical, stimulus])]). relacion([sujeto(['By', applying, a, reduction, 'voltage,', the, uncharged, 'Fc', can]), verbo([bind]), complemento([to, 'β-CD', that, is, immobilized, at, the, electrode, surface])]). relacion([sujeto(['Otherwise,', it, is, disassociated, from, the, surface, as, a, result, of, electrochemical, 'oxidation,', thus]), verbo([releasing]), complemento([the, captured, cells])]). relacion([sujeto(['Moreover,', because, 'Fc', can]), verbo([act]), complemento([as, an, electrochemical, probe, for, signal, 'readout,', the, integration, of, this, property, has, further, extended, the, ability, of, this, system, to, cell, detection])]). relacion([sujeto(['Electrochemical', signal]), verbo([has]), complemento([been, greatly, enhanced, for, cell, detection, by, introducing, branched, polymer, scaffold, that, are, carrying, large, quantities, of, 'Fc', moieties])]). relacion([sujeto(['It', is, anticipated, that, such, 'redox-controlled', system, can, be, an, important, tool, in, biological, and, biomedical, 'research,', especially, for, electrochemical]), verbo([stimulated]), complemento([tissue, engineering, and, 'cell-based', clinical, diagnosis])]). relacion([sujeto(['Long', noncoding, 'RNAs']), verbo([act]), complemento([as, crucial, regulators, in, plenty, of, human, 'cancers,', yet, their, potential, roles, and, molecular, mechanisms, in, chemoresistance, are, poorly, understood])]). relacion([sujeto(['This', study, showed, that, a, novel, 'lncRNA,', long, intergenic, noncoding, 'RNA', 152, '(', 'Linc00152', ')', ',']), verbo([promoted]), complemento([tumor, progression, and, conferred, resistance, to, oxaliplatin, '(', 'L-OHP)-induced', apoptosis, in, vitro, and, in, vivo])]). relacion([sujeto(['It', antagonized, chemosensitivity, through]), verbo([acting]), complemento([as, a, competing, endogenous, 'RNA', to, modulate, the, expression, of, 'miR-193a-3p,', and, then, 'erb-b2', receptor, tyrosine, kinase, 4, '(', 'ERBB4)'])]). relacion([sujeto(['Knockdown', of, 'ERBB4', in, colon, cancer, cells]), verbo([decreased]), complemento(['AKT', 'phosphorylation,', which, resulted, in, decreased, 'L-OHP', resistance])]). relacion([sujeto(['Consistent', with, above, 'findings,', the, specific, 'AKT', signaling, inhibitor, and, activator, were, 'used,', 'respectively,', which, demonstrated, that, 'Linc00152', contributed, to, 'L-OHP', resistance, at, least, partly, through]), verbo([activating]), complemento(['AKT', pathway])]). relacion([sujeto(['Further', studies, indicated, that, 'Linc00152', was]), verbo([increased]), complemento([and, appeared, to, be, an, independent, prognostic, factor, for, decreased, survival, and, increased, disease, recurrence, in, stage, 'II', and, 'III', colon, cancer, patients, undergoing, 'L-OHP-based', chemotherapy, after, surgery])]). relacion([sujeto(['Collectively,', our, findings, established, 'Linc00152', as, a, candidate, prognostic, indicator, of, outcome, and, drug, responsiveness, in, colon, cancer, 'patients,', and, the, involvement, of, competing, endogenous, 'RNAs', mechanism, in, 'Linc00152/miR-193a-3p/ERBB4/AKT', signaling, axis, may]), verbo([provide]), complemento([a, novel, choice, in, the, investigation, of, drug, resistance])]). relacion([sujeto(['The', rewarding, nature, of, many, forms, of, social, behavior, including, sexual, 'behavior,', parental, 'behavior,', and, social, play]), verbo([has]), complemento([been, revealed, using, 'well-established', procedures, such, as, the, conditioned, place, preference, test])]). relacion([sujeto(['Many', motivated, social, behaviors, are]), verbo([regulated]), complemento([by, the, nonapeptides, oxytocin, '(', 'OT)', and, arginine, vasopressin, '(', 'AVP)', through, their, actions, in, multiple, brain, structures])]). relacion([sujeto(['The', goal, of, the, present, study, was, to, investigate, the, role, of, 'OT', and, 'AVP', in, the, 'VTA', in]), verbo([regulating]), complemento([the, 'reward-like', properties, of, social, interactions])]). relacion([sujeto(['Interestingly,', 'however,', 'OT', and, 'AVP', injected, into, the, 'VTA']), verbo([induced]), complemento([a, significant, 'two-fold', reduction, in, place, avoidance, for, the, social, interaction, chamber, when, compared, to, control, injections, of, vehicle])]). relacion([sujeto(['Finally,', because, 'OT', and, 'AVP', can]), verbo([act]), complemento([on, each, 'other\'s', receptors, to, influence, social, 'behavior,', we, also, injected, highly, selective, 'OTR', and, 'V1aR', agonists, and, antagonists, to, determine, whether, 'OT', or, 'AVP', 'V1a', receptors, were, responsible, for, mediating, the, effects, of, these, neuropeptides, on, social, reward])]). relacion([sujeto(['Our', results, not, only, demonstrated, that, 'OT', and, 'AVP']), verbo([activate]), complemento(['OTRs', and, not, 'V1aRs', to, mediate, social, 'reward,', they, also, demonstrated, that, the, activation, of, 'OT', receptors, in, the, 'VTA', is, essential, for, the, expression, of, the, rewarding, properties, of, social, interactions])]). relacion([sujeto(['Moreover,', the, 'ECs', of, the, sprouts]), verbo([express]), complemento([various, levels, of, mRNA, for, 'Notch1', and, its, ligand, 'Dll4'])]). relacion([sujeto(['In', 'summary,', we, present, a, new, model, for, angiogenesis, studies]), verbo([involving]), complemento([mouse, 'PE', as, a, source, of, 'ECs'])]). relacion([sujeto(['We', believe, that, our, model, may]), verbo([act]), complemento([as, a, supplementary, assay, for, angiogenesis, studies, along, with, the, existing, models])]). relacion([sujeto(['Owing', to, their, unique, 'biological,', 'physical,', and, chemical, 'properties,', fluoroalkylated, organic, substances]), verbo([have]), complemento([attracted, significant, attention, from, researchers, in, a, variety, of, disciplines])]). relacion([sujeto(['Fluoroalkylated', compounds, are, considered, particularly, important, in, pharmaceutical, chemistry, because, of, their, superior, 'lipophilicity,']), verbo([binding]), complemento(['selectivity,', metabolic, 'stability,', and, bioavailability, to, those, of, their, nonfluoroalkylated, analogues])]). relacion([sujeto(['We']), verbo([have]), complemento([developed, various, methods, for, the, synthesis, of, fluoroalkylated, substances, that, rely, on, the, use, of, 'visible-light', photoredox, 'catalysis,', a, powerful, preparative, tool, owing, to, its, environmental, benignity, and, mechanistic, versatility, in, promoting, a, large, number, of, synthetically, important, reactions, with, high, levels, of, selectivity])]). relacion([sujeto(['In', this, 'Account,', we, describe, the, results, of, our, 'efforts,', which]), verbo([have]), complemento([led, to, the, development, of, 'visible-light', photocatalytic, methods, for, the, introduction, of, a, variety, of, fluoroalkyl, groups, '(', such, 'as,', -, 'CF3,', -, 'CF2R,', -, 'CH2CF3,', -, 'C3F7,', and, -, 'C4F9)', and, arylthiofluoroalkyl, groups, '(', such, 'as,', -, 'CF2SPh,', -, 'C2F4SAr,', and, -, 'C4F8SAr)', to, organic, substances])]). relacion([sujeto(['Notably,', we]), verbo([have]), complemento([observed, that, additives, significantly, affect, the, efficiencies, and, selectivities, of, these, reactions, and, can, even, change, the, outcome, of, the, reaction, by, playing, additional, roles, during, its, course])]). relacion([sujeto(['For', 'instance,', a, tertiary, amine, as, an, additive, in, the, reaction, medium, can]), verbo([act]), complemento([not, only, as, a, sacrificial, electron, donor, in, photoredox, catalysis, but, also, as, a, hydrogen, atom, 'source,', an, elimination, base, for, dehydrohalogenation, of, the, 'intermediate,', and, also, a, 'Brønsted', base, for, deprotonation])]). relacion([sujeto(['Vinca', alkaloids]), verbo([have]), complemento([been, approved, as, anticancer, drugs, for, more, than, 50, &, 'nbsp;years'])]). relacion([sujeto(['They']), verbo([have]), complemento([been, classified, as, cytotoxic, chemotherapy, drugs, that, act, during, cellular, 'mitosis,', enabling, them, to, target, fast, growing, cancer, cells])]). relacion([sujeto(['With', the, evolution, of, cancer, drug, development, there]), verbo([has]), complemento([been, a, shift, towards, new, &, 'quot;targeted"', therapies, to, avoid, the, side, effects, and, general, toxicities, of, &, 'quot;cytotoxic', 'chemotherapies"', such, as, the, vinca, alkaloids])]). relacion([sujeto(['Due', to, their, original, 'classification,', many]), verbo([have]), complemento([overlooked, the, fact, that, vinca, 'alkaloids,', taxanes, and, related, drugs, do, have, a, specific, molecular, 'target:', tubulin])]). relacion([sujeto(['In', this, 'review,', we, highlight, the, numerous, cellular, consequences, of, disrupting, microtubule, 'dynamics,', expanding, the, textbook, knowledge, of, microtubule, destabilising, agents, and]), verbo([providing]), complemento([novel, opportunities, for, their, use, in, cancer, therapy])]). relacion([sujeto(['Inflammation', in, 'Parkinson\'s', disease, '(', 'PD)', is, a, new, concept, that]), verbo([has]), complemento([gained, ground, due, to, the, potential, of, mitigating, dopaminergic, neuron, death, by, decreasing, inflammation])]). relacion([sujeto(['The', pathological, process, that, underlies, 'PD']), verbo([requires]), complemento([years, to, reach, its, full, extent])]). relacion([sujeto(['A', growing, body, of, evidence]), verbo([has]), complemento([been, accumulated, on, the, presence, of, multiple, inflammatory, signs, in, the, brain, of, 'PD', patients, even, in, very, late, stages, of, the, disease])]). relacion([sujeto(['We', showed, that, in, the, rat, model, of, 'PD/l-DOPA-induced', dyskinesia, there, was, an]), verbo([increased]), complemento([expression, of, inflammatory, 'markers,', such, as, the, enzymes, 'COX2', in, neurons, and, iNOS, in, glial, 'cells,', in, the, 'dopamine-denervated', striatum])]). relacion([sujeto(['The', gliosis, commonly, seem, in, 'PD', was]), verbo([associated]), complemento([with, modifications, in, astrocytes, and, microglia, that, occur, after, chronic, treatment, with, 'l-DOPA'])]). relacion([sujeto(['The', key, aims, of, current, 'PD', research, ought, to, be, to, elucidate, '(', 'a)', the, time, sequence, in, which, the, inflammatory, factors]), verbo([act]), complemento([in, 'PD', patient, brain, and, '(', 'b)', the, mechanisms, by, which, neuroinflammatory, response, contributes, to, the, collateral, effects, of, 'l-DOPA', treatment])]). relacion([sujeto(['Recombinant', 'TRAIL', and, agonistic, antibodies, to, death, receptors, '(', 'DRs)']), verbo([have]), complemento([been, in, clinical, trial, but, displayed, limited, 'anti-cancer', efficacy])]). relacion([sujeto(['We']), verbo([report]), complemento([here, that, chromatin, regulator, 'KDM4A/JMJD2A,', not, 'KDM4B,', has, a, pivotal, role, in, silencing, tumor, cell, expression, of, both, 'TRAIL', and, its, receptor, 'DR5'])]). relacion([sujeto(['In', 'TRAIL-sensitive', and, -, resistant, cancer, cells, of, 'lung,', breast, and, 'prostate,', 'KDM4A', 'small-molecule', inhibitor, 'compound-4', '(', 'C-4)', or, gene, silencing, strongly]), verbo([induces]), complemento(['TRAIL', and, 'DR5', 'expression,', and, causes, 'TRAIL-dependent', apoptotic, cell, death])]). relacion([sujeto(['C-4', alone, potently]), verbo([inhibits]), complemento([tumor, growth, with, marked, induction, of, 'TRAIL', and, 'DR5', expression, in, the, treated, tumors, and, effectively, sensitizes, them, to, the, newly, developed, 'TRAIL-inducer', 'ONC201'])]). relacion([sujeto(['Mechanistically,', 'C-4', does, not, appear, to]), verbo([act]), complemento([through, the, 'Akt-ERK-FOXO3a', pathway])]). relacion([sujeto(['Instead,', it, switches, histone, modifying, enzyme, complexes, at, promoters, of, 'TRAIL', and, 'DR5', transcriptional, activator, 'CHOP', gene, by, dissociating, 'KDM4A', and]), verbo([nuclear]), complemento([receptor, corepressor, '(', 'NCoR)-HDAC', complex, and, inducing, the, recruitment, of, histone, acetylase, 'CBP'])]). relacion([sujeto(['Thus,', our, results]), verbo([reveal]), complemento(['KDM4A', as, a, key, epigenetic, silencer, of, 'TRAIL', and, 'DR5', in, tumors, and, establish, inhibitors, of, 'KDM4A', as, a, novel, strategy, for, effectively, sensitizing, tumors, to, 'TRAIL', 'pathway-based', therapeutics])]). relacion([sujeto(['Since', the, beginning, of, this, 'century,', 'π-Lewis', acidic, gold, complexes]), verbo([have]), complemento([become, the, catalysts, of, choice, for, a, wide, range, of, organic, 'reactions,', especially, those, involving, nucleophilic, addition, to, 'carbon-carbon', multiple, bonds])]). relacion([sujeto(['In', order, to, address, this, limitation, and, expand, the, scope, of, gold, catalysis, beyond, conventional, 'hydrofunctionalization,', extensive, efforts]), verbo([have]), complemento([been, made, to, develop, new, oxidative, reactions, using, strong, external, oxidants, capable, of, overcoming, the, high, potential, of, the, 'Au(I)/Au(III)', redox, couple])]). relacion([sujeto(['However,', these, processes, typically]), verbo([require]), complemento([superstoichiometric, amounts, of, the, oxidant, and, proceed, under, relatively, harsh, conditions])]). relacion([sujeto(['Moreover,', to, 'date,', 'gold-catalyzed', oxidative, coupling, reactions]), verbo([have]), complemento([remained, somewhat, limited, in, scope, 'because,', for, many, 'systems,', the, desired, 'cross-coupling', does, not, favorably, compete, with, homodimerization, or, conventional, hydrofunctionalization])]). relacion([sujeto(['In', 2013, ',', we, disclosed, a, new, concept, for, 'gold-catalyzed', coupling, reactions, 'that,', rather, than]), verbo([involving]), complemento([external, 'oxidants,', employs, aryl, radicals, that, act, as, both, the, oxidant, and, the, coupling, partner, in, overall, 'redox-neutral', transformations])]). relacion([sujeto(['Using', aryldiazonium, 'salts,', which, are, known, to]), verbo([act]), complemento([as, sources, of, aryl, radicals, upon, activation, with, reducing, 'photocatalysts,', we, could, achieve, intramolecular, 'oxy-', and, aminoarylations, of, alkenes, upon, irradiating, the, reaction, mixtures, with, visible, light])]). relacion([sujeto(['The', potential, of, dual, 'gold/photoredox', catalysis, was, quickly, realized, by, several, research, groups, and, a, range, of, diverse, new, coupling, reactions]), verbo([involving]), complemento([nucleophilic, addition, to, 'π-systems', and, even, 'P-H', and, 'C(sp)-H', functionalization, have, been, developed])]). relacion([sujeto(['Furthermore,', when, gold, complexes, that, are, not, catalytically, active, prior, to, oxidation, by, the, aryl, radical, are, 'employed,', background, reactions, not]), verbo([involving]), complemento([coupling, can, be, suppressed])]). relacion([sujeto(['Notably,', this, feature]), verbo([has]), complemento([allowed, for, the, successful, use, of, allenes, and, 'alkynes,', for, which, conventional, hydrofunctionalization, pathways, are, highly, 'favored,', opening, the, door, to, new, transformations, involving, the, most, common, substrate, classes, for, gold, catalysis])]). relacion([sujeto(['In', this, 'Account,', we]), verbo([provide]), complemento([an, overview, of, dual, 'gold/photoredox', catalysis, and, highlight, the, potential, of, this, concept, to, greatly, expand, the, scope, of, homogeneous, gold, catalysis, and, enable, the, efficient, construction, of, complex, organic, molecules])]). relacion([sujeto(['Moreover,', recent, studies, on, the, visible, 'light-promoted', synthesis, of, novel, 'gold(III)', complexes]), verbo([suggest]), complemento([that, photoredox, activation, could, yet, find, further, applications, in, gold, chemistry, beyond, coupling])]). relacion([sujeto(['Ataxin-2', '(', 'ATXN2)', polyglutamine, domain, expansions, of, large, size, result, in, an, autosomal, dominantly, inherited, 'multi-system-atrophy', of, the, nervous, system, named, spinocerebellar, ataxia, type, 2, '(', 'SCA2),', while, expansions, of, intermediate, size]), verbo([act]), complemento([as, polygenic, risk, factors, for, motor, neuron, disease, '(', 'ALS', and, 'FTLD)', and, perhaps, also, for, 'Levodopa-responsive', 'Parkinson\'s', disease, '(', 'PD)'])]). relacion([sujeto(['Conversely,', expression, of, 'Pink1', was, severely]), verbo([decreased]), complemento([upon, global, transcriptome, profiling, of, 'Atxn2-knockout', mouse, cerebellum, and, 'liver,', in, parallel, to, strong, effects, on, 'Opa1', and, 'Ghitm,', which, encode, known, mitochondrial, dynamics, regulators])]). relacion([sujeto(['Starvation', stress, of, human, 'SH-SY5Y', neuroblastoma, cells]), verbo([led]), complemento([to, a, transcriptional, phasic, induction, of, 'ATXN2', in, parallel, to, 'PINK1,', and, the, knockdown, of, one, enhanced, the, expression, of, the, other, during, stress, response])]). relacion([sujeto(['These', findings]), verbo([suggest]), complemento([that, 'ATXN2', may, modify, the, known, 'PINK1', roles, for, mitochondrial, quality, control, and, autophagy, during, cell, stress])]). relacion([sujeto(['Given', that, 'PINK1', is, responsible, for, autosomal, recessive, juvenile, 'PD,', this, genetic, interaction]), verbo([provides]), complemento([a, concept, how, the, degeneration, of, nigrostriatal, dopaminergic, neurons, and, the, 'Parkinson', phenotype, may, be, triggered, by, 'ATXN2', mutations])]). relacion([sujeto(['The', heterodimeric, receptor, tyrosine, kinase, complex, formed, by, 'HER2', and, 'HER3', can]), verbo([act]), complemento([as, an, oncogenic, driver, and, is, also, responsible, for, rescuing, a, large, number, of, cancers, from, a, diverse, set, of, targeted, therapies])]). relacion([sujeto(['Inhibitors', of, these, 'proteins,', particularly, 'HER2,']), verbo([have]), complemento([dramatically, improved, patient, outcomes, in, the, 'clinic,', but, recent, studies, have, demonstrated, that, stimulating, the, heterodimeric, 'complex,', either, via, growth, factors, or, by, increasing, the, concentrations, of, 'HER2', and, 'HER3', at, the, 'membrane,', significantly, diminishes, the, activity, of, the, inhibitors])]). relacion([sujeto(['Medicinal', chemistry, on, the, hit, scaffold, resulted, in, a, previously, uncharacterized, inhibitor, that]), verbo([acts]), complemento([through, preferential, inhibition, of, the, active, state, of, 'HER2', 'and,', as, a, 'result,', is, able, to, overcome, cellular, mechanisms, of, resistance, such, as, growth, factors, or, mutations, that, stabilize, the, active, form, of, 'HER2'])]). relacion([sujeto(['Non-destructive', protocols, which, can, define, a, 'biomaterial\'s', degradation, and, its]), verbo([associated]), complemento([ability, to, support, proliferation, 'and/or', promote, extracellular, matrix, deposition, will, be, an, essential, in, vitro, tool])]). relacion([sujeto(['Changes', in, fluorescence, of, the, biomaterials, and, the]), verbo([release]), complemento([of, fluorescent, soluble, 'by-products', were, confirmed, as, accurate, methods, to, quantify, degradation])]). relacion([sujeto(['It', was, demonstrated, that]), verbo([increasing]), complemento([rates, of, the, selected, 'biomaterials\'', degradation, led, to, a, decrease, in, cell, proliferation, and, concurrently, an, increase, in, osteogenic, matrix, production])]). relacion([sujeto(['This', 'TI', was, further, validated, using, an, ex, vivo, chick, femur, 'model,', where, the, faster, degrading, 'biomaterial,', 'fibrin,']), verbo([led]), complemento([to, an, increased, 'TI', for, mineralisation, within, an, epiphyseal, defect])]). relacion([sujeto(['This', in, vitro, 'tool,', 'TI,', for, monitoring, the, effect, of, biomaterial, degradation, on, extracellular, matrix, production, may, well]), verbo([act]), complemento([as, predictor, of, the, selected, 'biomaterials\'', performance, during, in, vivo, studies])]). relacion([sujeto(['We']), verbo([have]), complemento([discovered, some, novel, comparative, findings, that, cells, cultured, on, biomaterials, with, increased, rates, of, degradation, have, lower, rates, of, proliferation, but, alternatively, have, a, greater, production, of, osteogenic, markers, compared, to, materials, which, degrade, slower])]). relacion([sujeto(['Accumulating', evidence, indicates, that, miRNAs, play, critical, roles, in, prostate, cancer, '(', 'PCa)', metastasis, and]), verbo([have]), complemento([potential, use, as, therapeutic, targets])]). relacion([sujeto(['Although', dysregulated, 'miR-132/212']), verbo([have]), complemento([been, suggested, to, be, directly, involved, in, the, proliferation, and, invasion, of, multiple, 'malignancies,', the, exact, role, of, 'miR-132/212', in, 'PCa', has, not, yet, been, fully, understood])]). relacion([sujeto(['Bioinformatics', tools, and, luciferase, reporter, assay, were, utilized, to, identify, the, molecular]), verbo([target]), complemento([of, 'miR-132/212'])]). relacion([sujeto(['Functionally,', upregulation, of, 'miR-132/212']), verbo([inhibits]), complemento([the, migration, and, invasive, capacity, of, 'Vcap', and, 'Lncap', cells, by, 'wound-healing', and, transwell, 'assays,', respectively])]). relacion([sujeto(['Notably,', overexpression, of, 'miR-132/212', could]), verbo([inhibit]), complemento(['TGF-β', '(', transforming, growth, 'factor-β)-induced', 'EMT', in, 'Vcap', and, 'Lncap', cells, at, both, the, mRNA, and, protein, expression, levels])]). relacion([sujeto(['SOX4', 'gene,', an, important, 'EMT', regulator, of, 'PCa,', was, identified, as, the]), verbo([target]), complemento([of, 'miR-132/212', by, bioinformatics, tools, and, luciferase, reporter, assay])]). relacion([sujeto(['Our', data]), verbo([suggested]), complemento([that, 'miR-132/212', may, act, as, tumor, suppressors, in, 'PCa', progression, through, disrupting, 'EMT', process, by, directly, targeting, 'SOX4'])]). relacion([sujeto(['The', aim, of, this, study, was, to, use, 'Kotter\'s']), verbo([leading]), complemento([change, model, to, explore, the, implementation, of, workplace, health, and, wellbeing, initiatives])]). relacion([sujeto(['Although', none, of, the, workplaces]), verbo([reported]), complemento([using, a, formal, organizational, change, model, when, implementing, their, healthy, workplace, 'initiatives,', there, did, appear, to, be, perceived, merit, in, using, the, steps, in, 'Kotter\'s', model])]). relacion([sujeto(['Commercially', available, 'Ni(II)', 'salts,', 'Ni(acac)2', '(', acac, =, 'acetylacetonato)', and, its, derivatives, 'bis(hexafluoroacetylacetonato)nickel(II)', and, bis, '(', 2, ',', 2, ',', 6, ',', 6, -, 'tetramethyl-3,5-heptanedionato)nickel(II),', also]), verbo([act]), complemento([as, versatile, hydrosilylation, catalyst, precursors, in, the, presence, of, 'NaBHEt3'])]). relacion([sujeto(['Responsible', transparency, helps, to]), verbo([promote]), complemento([integrity, between, industry, and, researchers, and, has, the, potential, to, increase, public, trust])]). relacion([sujeto(['As', part, of, its, inevitable, 'evolution,', the, 'Open', 'Payments', database, is, likely, to]), verbo([have]), complemento([opportunities, to, increase, and, improve, the, context, around, the, data, that, it, 'reports,', thus, leading, to, a, decrease, in, the, currently, encountered, confusion, and, misinterpretation, of, the, data])]). relacion([sujeto(['The', arboviruses, 'West', 'Nile', virus, '(', 'WNV),', dengue, virus, '(', 'DENV)', and, 'Ross', 'River', virus, '(', 'RRV)']), verbo([have]), complemento([been, demonstrated, to, be, blood, 'transfusion-transmissible'])]). relacion([sujeto(['A', model, to, estimate, the, risk, of, 'WNV', to, the, blood, supply, using, a, 'Monte', 'Carlo', approach]), verbo([has]), complemento([been, developed, and, also, applied, to, 'Chikungunya', virus])]). relacion([sujeto(['The', extremely, crowded, cytoplasm]), verbo([promotes]), complemento([macromolecular, 'self-assembly', and, formation, of, distinct, subcellular, 'structures,', which, perform, specialized, functions])]). relacion([sujeto(['For', 'example,', the, cell, poles]), verbo([act]), complemento([as, hubs, for, signal, transduction, 'complexes,', thus, providing, a, platform, for, the, coordination, of, optimal, cellular, responses, to, environmental, cues])]). relacion([sujeto(['Distribution', of, macromolecules, is, mostly]), verbo([mediated]), complemento([via, specialized, transport, 'machineries,', including, the, 'MreB', cytoskeleton])]). relacion([sujeto(['Alpha-2', adrenergic, receptors]), verbo([target]), complemento([several, behavioral, functions])]). relacion([sujeto(['These', receptors, may, connect, with, the, brain, pathways]), verbo([mediating]), complemento([sensorimotor, gating, system, that, associate, with, 'psychoses,', and, the, literature, that, investigate, the, relationship, between, 'alpha-2', receptors, and, sensorimotor, gating, system, is, very, limited, and, some, results, are, controversial])]). relacion([sujeto(['Because', idazoxan, and, clonidine, also]), verbo([act]), complemento([through, imidazoline, 'receptors,', our, results, suggest, that, 'alpha-2', 'and/or', imidazoline, receptors, are, associated, with, 'PPI', of, acoustic, startle, reflex, in, rats])]). relacion([sujeto(['Stimulation', of, these, receptors, may]), verbo([cause]), complemento([sensorimotor, gating, disturbances])]). relacion([sujeto(['The', development, of, new, molecules, able, to, efficiently]), verbo([act]), complemento([as, 'long-circulating', computed, tomography, '(', 'CT)', contrast, agents, is, one, of, the, most, crucial, topics, in, the, biomedical, field])]). relacion([sujeto(['Gold', nanoparticles, '(', 'AuNPs)']), verbo([have]), complemento([showed, unique, 'X-rays', attenuation, properties, 'which,', combined, with, their, easy, surface, 'functionalization,', makes, them, ideal, candidates, for, the, next, generation, of, contrast, agents])]). relacion([sujeto(['Their', activity, as, efficient, and, reliable, 'CT', contrast, agents]), verbo([has]), complemento([been, evaluated, and, compared])]). relacion([sujeto(['Moreover,', 'glucosamine-functionalized', gold, nanoparticles]), verbo([have]), complemento([been, developed, '(', '[', 'Au]', =, 31.2, 'mg/mL;', 'HU', =, 2453, ')', ',', in, order, to, obtain, a, 'CT', contrast, agent, able, to, combine, spatial, resolution, with, metabolic, information])]). relacion([sujeto(['Anti-biofilm', peptides, represent, a, very, promising, approach, to, treat, 'biofilm-related', infections, and]), verbo([have]), complemento([an, extraordinary, ability, to, interfere, with, various, stages, of, the, biofilm, growth, mode])]). relacion([sujeto(['Anti-biofilm', peptides, possess, promising, 'broad-spectrum', activity, in, killing, both, 'Gram-positive', and, 'Gram-negative', bacteria, in, 'biofilms,', show, strong, synergy, with, conventional, 'antibiotics,', and]), verbo([act]), complemento([by, targeting, a, universal, stringent, stress, response])]). relacion([sujeto(['Understanding', downstream, processes, at, the, molecular, level, will, help, to, develop, and, design, peptides, with]), verbo([increased]), complemento([activity])]). relacion([sujeto(['Through', semistructured, 'interviews,', researchers, explored, concerns, and, perspectives, of, 30, 'PCPs', on, receiving, and]), verbo([acting]), complemento([on, incidental, imaging, findings])]). relacion([sujeto(['Other', 'PCPs', did, not]), verbo([act]), complemento([on, findings, that, were, unfamiliar, or, occurred, in, an, unusual, clinical, context, when, 'follow-up', recommendations, were, not, 'given;', the, challenges, of, researching, the, clinical, importance, of, these, findings, or, seeking, specialist, consultation, led, to, inaction])]). relacion([sujeto(['Some', 'PCPs']), verbo([reported]), complemento([using, a, uniform, approach, to, communicate, and, manage, incidental, 'findings,', while, others, adapted, their, approach, to, the, patient, and, the, finding])]). relacion([sujeto(['These', results]), verbo([suggest]), complemento([that, some, patients, may, receive, inappropriate, 'follow-up', of, incidental, imaging, findings, and, present, an, opportunity, for, radiologists, to, help, 'PCPs', and, patients, to, best, use, the, information, conveyed, in, imaging, reports])]). relacion([sujeto(['A', combination, of, 'anti-TLR2', mAB, and, 'anti-TLR4', mAB, showed, that, both, receptors, drive, 'IP-10', and, 'KC', levels, and, that, there, is, cooperation, for]), verbo([increases]), complemento([in, 'IL-6,', 'MIG,', and, 'MCP-1', levels, between, 'TLR2', and, 'TLR4'])]). relacion([sujeto(['These', data, also, support, the, conclusion, that, 'TLR2', and, 'TLR4']), verbo([act]), complemento([in, concert, as, important, receptors, in, the, host, immune, response, to, 'H/R'])]). relacion([sujeto(['Results', 'Flow', volumes, significantly]), verbo([increased]), complemento([in, the, 'SMV', '(', 0.24, 'L/min;', 95, '%', confidence, interval, '[', 'CI]:', 0.07, ',', 0.41, ')', ',', 'SV', '(', 0.31, 'L/min;', 95, '%', 'CI:', 0.07, ',', 0.54, ')', ',', and, 'PV', '(', 0.88, 'L/min;', 95, '%', 'CI:', 0.06, ',', 1.7, ')', after, 'TIPS', placement, '(', all, 'P', &, 'lt;'])]). relacion([sujeto(['Tau', immunotherapy]), verbo([has]), complemento([emerged, as, a, promising, approach, to, clear, tau, aggregates, from, the, brain])]). relacion([sujeto(['Our', previous, findings]), verbo([suggest]), complemento([that, tau, antibodies, may, act, outside, and, within, neurons, to, promote, such, clearance])]). relacion([sujeto(['We']), verbo([have]), complemento([developed, an, approach, using, flow, 'cytometry,', a, human, neuroblastoma, 'cell model', overexpressing, tau, with, the, 'P301L', 'mutation,', and, paired, helical, filament, '(', 'PHF)-enriched', pathologic, tau, to, effectively, screen, uptake, and, retention, of, tau, antibodies, in, conjunction, with, 'PHF'])]). relacion([sujeto(['Our', data, demonstrates, a, marked]), verbo([decrease]), complemento([in, the, incidence, of, 'NSF', after, education, of, our, referring, 'physicians,', implementation, of, clinical, screening, 'process,', and, change, to, gadobenate, dimeglumine, from, gadodiamide, in, patients, with, renal, insufficiency])]). relacion([sujeto(['This', approach, potentially]), verbo([provides]), complemento([an, acceptable, 'risk-benefit', profile, for, patients, with, renal, insufficiency, that, required, 'MR', imaging, for, clinical, care])]). relacion([sujeto(['Dual-function', sRNAs, are, a, subgroup, of, small, regulatory, 'RNAs', that]), verbo([act]), complemento([on, the, one, hand, as, 'base-pairing', sRNAs, to, inhibit, or, activate, target, gene, expression, and, on, the, other, hand, as, 'peptide-encoding', mRNAs, that, function, either, in, the, same, or, in, another, metabolic, pathway])]). relacion([sujeto(['Furthermore,', we, summarize, the, data, available, on, five, potential, 'dual-function', 'sRNAs,', whose, 'base-pairing', function, is, well, established, whereas, the, role, of, their, encoded, peptides]), verbo([has]), complemento([not, yet, been, elucidated])]). relacion([sujeto(['In', 'addition,', we]), verbo([provide]), complemento([three, examples, for, 'RNAs', with, more, than, one, function, that, do, not, fall, into, the, 'above-mentioned', category])]). relacion([sujeto(['With', the, application, of, 'RNAseq,', peptidomics, and, transcriptomics, it, can, be, expected, that, the, number, of, 'dual-function', sRNAs, will, considerably]), verbo([increase]), complemento([within, the, next, 'years,', thus, enhancing, our, knowledge, on, the, regulatory, potential, of, these, 'RNAs'])]). relacion([sujeto(['The', purpose, of, this, study, was, to, characterize, the, secretion, profile, of]), verbo([induced]), complemento([pluripotent, stem, 'cell-derived', retinal, pigment, epithelium, '(', 'iPS-RPE)', during, wound, healing])]). relacion([sujeto(['We', hypothesized, that, 'iPS-RPE', secretes, cytokines, and, growth, factors, which]), verbo([act]), complemento([in, an, autocrine, manner, to, promote, migration, and, proliferation, of, cells, during, wound, healing])]). relacion([sujeto(['The', monolayers, were, scratched, to]), verbo([induce]), complemento([a, wound])]). relacion([sujeto(['The', proteins, were]), verbo([found]), complemento([to, be, secreted, in, a, polarized, manner])]). relacion([sujeto(['The', conditioned, medium, from, wounded, monolayers]), verbo([promoted]), complemento([collagen, gel, 'contraction,', as, well, as, proliferation, and, migration, of, 'ARPE', 19, cells])]). relacion([sujeto(['These', results, indicate, that, after, the, monolayer, is, 'wounded,', 'iPS-RPE', secretes, proteins, into, the, culture, medium, that]), verbo([promote]), complemento([increased, 'proliferation,', 'contraction,', and, migration])]). relacion([sujeto(['Advancements', in, adoptive, cell, transfer, therapy, '(', 'ACT)']), verbo([has]), complemento([led, to, the, use, of, 'T', cells, engineered, with, tumor, specific, 'T', cell, 'receptors,', which, after, rapid, expansion, can, be, obtained, in, sufficient, numbers, for, treating, patients])]). relacion([sujeto(['However,', due, to, massive, proliferation, these, cells, are, close, to, replicative, 'senescence,', exhibit, exhausted, 'phenotype,', and, also, display]), verbo([increased]), complemento([susceptibility, to, activation, induced, cell, death])]). relacion([sujeto(['We']), verbo([have]), complemento([previously, shown, that, tumor, reactive, 'T', cells, undergo, 'caspase-independent', cell, death, upon, 'TCR', restimulation, with, cognate, 'antigen,', which, involves, reactive, oxygen, species, and, 'c-jun', 'N-terminal', kinase])]). relacion([sujeto(['As', compared, to, the, 'T', central, memory, '(', 'TCM)', 'subsets,', the, 'TEM', subset, displayed, an]), verbo([increased]), complemento([expression, of, genes, involved, in, necroptotic, cell, 'death,', and, a, necrotic, phenotype, upon, 'TCR', restimulation, as, confirmed, by, electron, microscopy])]). relacion([sujeto(['Higher', expression, of, 'receptor-interacting', kinases, '(', 'RIPK)', that]), verbo([mediate]), complemento([necroptosis, was, also, observed, in, the, 'TEM', fraction])]). relacion([sujeto(['Importantly,', 'NecroX2', pretreated, tumor, reactive, 'T', cells, also, exhibited, better, tumor, control, and]), verbo([increased]), complemento([in, vivo, persistence, when, 'adoptively-transferred', to, treat, subcutaneously, established, murine, melanoma, 'B16-F10'])]). relacion([sujeto(['Thus,', it, is, likely, that, the, outcome, of, 'ACT', could, be, vastly, improved, by, interfering, with, the, necroptotic, cell, death, pathway, in]), verbo([activated]), complemento([tumor, reactive, 'T', cells, used, in, immunotherapy])]). relacion([sujeto(['BACE1', is, an, aspartyl, protease, which, is, a, therapeutic]), verbo([target]), complemento([for, 'Alzheimer\'s', disease, '(', 'AD)', because, of, its, participation, in, the, 'rate-limiting', step, in, the, production, of, 'Aβ-peptide,', the, accumulation, of, which, produces, senile, plaques, 'and,', in, 'turn,', the, neurodegenerative, effects, associated, with, 'AD'])]). relacion([sujeto(['Additionally,', the, catalytic, site]), verbo([has]), complemento([been, found, to, be, covered, by, an, antiparallel, hairpin, loop, called, the, flap])]). relacion([sujeto(['Subsequent', interaction, with, the, ligand]), verbo([induces]), complemento([flap, closure, and, the, stabilization, of, the, macromolecular, complex])]). relacion([sujeto(['Additionally,', differences, in, their, capacities, to, establish, and]), verbo([maintain]), complemento([interactions, with, residues, such, as, 'Asp93,', 'Gly95,', 'Thr133,', 'Asp289,', 'Gly291,', and, 'Asn294', during, this, step, allow, differentiation, among, the, inhibitory, activities, of, the, 'HEAs'])]). relacion([sujeto(['The', results, and, methodology, here]), verbo([reported]), complemento([will, serve, to, elucidate, the, inhibitory, pathway, of, other, families, of, compounds, that, act, as, 'BACE1', 'inhibitors,', as, well, as, the, design, of, better, leader, compounds, for, the, treatment, of, 'AD'])]). relacion([sujeto(['However,', few, studies]), verbo([have]), complemento([investigated, urban, watersheds, of, 'non-point', sources])]). relacion([sujeto([8, ')', of, efflux, pumps, with, antimicrobial, biosynthesis, genes]), verbo([suggest]), complemento([that, natural, production, of, antimicrobials, may, act, as, a, selective, pressure, of, transporter, proteins, in, the, absence, of, antibiotics, from, anthropogenic, sources])]). relacion([sujeto(['In', 'conclusion,', distinct, antibiotic, resistant, bacteria, phylotypes, and, a, variety, of, 'ARGs', were, present, in, the, 'non-point', sources, urban, watersheds, of, different, 'land-use', 'profiles,']), verbo([suggesting]), complemento([that, 'ARG', risk, assessments, and, monitoring, studies, need, to, include, these, types, of, watersheds])]). relacion([sujeto(['They']), verbo([act]), complemento([as, storage, sites, for, translationally, silenced, mRNAs, under, stress, conditions])]). relacion([sujeto(['During', viral, 'infection,', 'SG', formation, results, in, the, modulation, of, innate, antiviral, immune, 'responses,', and, several, viruses]), verbo([have]), complemento([the, ability, to, either, promote, or, prevent, 'SG', assembly])]). relacion([sujeto(['Here,', we, show, that, rabies, virus, '(', 'RABV)']), verbo([induces]), complemento(['SG', formation, in, infected, 'cells,', as, revealed, by, the, detection, of, 'SG-marker', proteins, 'Ras', 'GTPase-activating', 'protein-binding', protein, 1, '(', 'G3BP1),', 'T-cell', intracellular, antigen, 1, '(', 'TIA-1)', and, 'poly(A)-binding', protein, '(', 'PABP)', in, the, 'RNA', granules, formed, during, viral, infection])]). relacion([sujeto(['As', shown, by, live, cell, 'imaging,', 'RABV-induced', 'SGs', are, highly, dynamic, structures, that]), verbo([increase]), complemento([in, 'number,', grow, in, size, by, fusion, 'events,', and, undergo, 'assembly/disassembly', cycles])]). relacion([sujeto(['Three', dimensional, reconstructions]), verbo([reveal]), complemento([that, both, structures, remain, distinct, even, when, they, are, in, close, contact])]). relacion([sujeto(['In', 'addition,', viral, mRNAs, synthesized, in, 'NBs', accumulate, in, the, 'SGs', during, viral, 'infection,']), verbo([revealed]), complemento([material, exchange, between, both, compartments])]). relacion([sujeto(['Although', 'RABV-induced', 'SG', formation, is, not, affected, in, 'MEFs', lacking, 'TIA-1,', 'TIA-1', depletion]), verbo([promotes]), complemento([viral, translation, which, results, in, an, increase, of, viral, replication, indicating, that, 'TIA-1', has, an, antiviral, effect])]). relacion([sujeto(['Inhibition', of, 'PKR', expression, significantly]), verbo([prevents]), complemento(['RABV-SG', formation, and, favors, viral, replication, by, increasing, viral, translation])]). relacion([sujeto(['This', is, correlated, with, a, drastic, inhibition, of, 'IFN-B', gene, expression, indicating, that, 'SGs', likely]), verbo([mediate]), complemento([an, antiviral, response, which, is, however, not, sufficient, to, fully, counteract, 'RABV', infection])]). relacion([sujeto(['Interviews']), verbo([found]), complemento([that, 'ACA', preparation, focused, on, enrollment, 'growth,', 'staffing,', competition, among, health, 'plans,', concern, about, cost, 'sharing,', and, 'HIV', 'pre-exposure', prophylaxis, '(', 'PrEP)', services])]). relacion([sujeto(['Quantitative', analyses]), verbo([found]), complemento([that, 'post-ACA', 'HIV-positive', patient, enrollment, grew])]). relacion([sujeto(['New', enrollees, in, 2014, were, more, likely, than, 2012, enrollees, to, be, enrolled, in, 'high-deductible', plans, '(', 'P', &, 'lt;', 0.01, ')', or, through, 'Medicaid', '(', 'P', &, 'lt;', 0.01, ')', ',', and, marginally, more, likely, to]), verbo([have]), complemento([better, 'HIV', viral, control, '(', 'P', &, 'lt;', 0.1, ')'])]). relacion([sujeto(['They', also, were, more, likely, to, be, diagnosed, with, asthma, '(', 'P', &, 'lt;', 0.01, ')', or, substance, use, disorders, '(', 'P', &, 'lt;', 0.05, ')', and, to]), verbo([have]), complemento([used, primary, care, health, services, in, the, 6, months, postenrollment, '(', 'P', &, 'lt;', 0.05, ')', than, the, 'pre-ACA', cohort])]). relacion([sujeto(['The']), verbo([increasing]), complemento([detection, of, papillary, thyroid, microcarcinoma, '(', 'PTMC)', has, created, management, dilemmas])]). relacion([sujeto(['To', clarify, the, clinical, significance, of, postsurgery]), verbo([stimulated]), complemento([thyroglobulin, '(', 'ps-Tg)', in, 'PTMC', who, undergo, thyroidectomy, and, radioactive, iodine, '(', 'RAI),', we, retrospectively, reviewed, the, 358, 'PTMC', patients, who, were, treated, with, 'RAI', and, followed, up, in, our, hospital])]). relacion([sujeto(['Five', variables, '(', male, 'sex,', nonconcurrent, benign, 'pathology,', initial, tumor, size, &, 'gt;5', 'mm,', lymph, node, 'metastasis,', and, 'ps-Tg', '≥', 10, 'μg/L)', were]), verbo([associated]), complemento([with, disease, persistence, by, univariate, regression, analysis])]). relacion([sujeto(['Therefore,', 'PTMC', with, a, small, size, of, '≤1', cm, does, not, always]), verbo([act]), complemento([as, an, indolent, tumor])]). relacion([sujeto(['In', 'conclusion,', 'ps-Tg', '≥', 10, 'μg/L', is]), verbo([associated]), complemento([with, increased, odds, of, disease, persistence])]). relacion([sujeto(['This', foundation, of, treatment]), verbo([has]), complemento([a, high, rate, of, biochemical, and, clinical, response, and, meaningful, clinical, benefit, but, is, finite, in, duration, as, most, cancers, will, progress, to, castration, resistance])]). relacion([sujeto(['Deciphering', what, steroidogenic, enzymes, are, overactive, and]), verbo([required]), complemento([for, 'testosterone/dihydrotestosterone', synthesis, has, yielded, therapies, directed, toward, both, adrenal, and, 'tumor-derived', androgens])]). relacion([sujeto(['All', androgens, normally]), verbo([act]), complemento([through, 'AR,', and, this, fact, remains, true, in, mCRPC])]). relacion([sujeto(['The', cancer, accomplishes, this, by, overexpressing, the, receptor, '(', by, genomic, 'copy-number']), verbo([gains]), complemento([or, 'RNA', 'amplification),', mutating, it, directly, to, lose, its, selectivity, for, 'testosterone/dihydrotestosterone,', or, selecting, for, splice, variants, that, do, not, require, ligand, at, all])]). relacion([sujeto(['Through', this, 'understanding,', drugs]), verbo([targeting]), complemento(['non-ligand-binding', aspects, of, 'AR', functioning, '(', e])]). relacion([sujeto([',']), verbo([nuclear]), complemento(['translocation,', cofactor, 'recruitment)', have, been, developed])]). relacion([sujeto(['Finally,', how, 'AR']), verbo([interacts]), complemento([with, other, signaling, pathway, is, being, 'explored,', and, new, combinations, of, targets, to, test, are, being, proposed])]). relacion([sujeto(['Multiple', compounds, remain, in, various, stages, of, clinical, development, based, on]), verbo([targeting]), complemento([these, resistance, 'pathways,', and, 'hopefully,', they, will, further, the, armamentarium, for, mCRPC])]). relacion([sujeto(['Here,', it, is]), verbo([reported]), complemento([that, the, 1, 'D', 'connected/aggregated', vacancies, are, energetically, stable, at, room, temperature])]).